[
  {
    "caption": "(a) Intracellular spermidine of five-day-oldΔspe1 cells, compared with wild-type cells. Data represent means ± s.e.m. (n = 3; *P 0.001).",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(b) Chronological ageing of wild-type (▪, o) and polyamine-depleted Δspe1 (▴, ▿) yeast cells with (open symbols) and without (closed symbols) supplementation of low doses of spermidine. Data represent means ± s.e.m. (n = 4). Cells were tested for cell death markers at day 3.",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(c) Fluorescence microscopy of DHE→Eth conversion in wild-type and Δspe1 cells indicating ROS production. Scale bars, 10 μm.",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(d) Quantification (FACS analysis) of ROS accumulation using DHE→Eth conversion of wild-type (WT) and Δspe1 cells with and without supplementation of low doses of spermidine. Data represent means ± s.e.m. (n = 4; *P 0.001).",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(e) Quantification (FACS analysis) of phosphatidylserine externalization and loss of membrane integrity using annexin V/PI co-staining (at day 5) and of DNA fragmentation using TUNEL staining (at day 3) of chronologically ageing wild-type (WT) and Δspe1 cells with or without supplementation of 0.1 mM spermidine as indicated. Data represent means ± s.e.m. (n = 3; *P 0.001).",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(e) Fluorescence microscopy of chronologically aged wild-type cells (day 3 and 14) expressing an EGFP-tagged version of the yeast HMGB1 homologue (Nhp6A-EGFP) with or without (control) addition of 4 mM spermidine. Scale bars, 5 μm.",
    "ncbi_link": "HMGB1: 3146
Nhp6A: 856165"
  },
  {
    "caption": "(c) Relative acetylation (normalized to wild-type controls at each day) of indicated histone H3 Lys residues of Δspe1 cells (open bars), compared with wild-type cells (closed bars) during chronological ageing. Data represent means ± s.e.m. (n = 3). P values indicate the result of a two-factor ANOVA corrected by Bonferroni post hoc test.",
    "ncbi_link": "spe1: 853651"
  },
  {
    "caption": "(a) Relative acetylation of histone H3 Lys 9 and 14 residues determined by quantification of immunoblot analysis performed at day 20 of the ageing experiment shown in panel b. Data represent means ± s.e.m. (n = 3; *P 0.05). (b) Chronological ageing of wild-type (▪, o) and Δiki3Δsas3 (▴, ▿) with (open symbols) or without (closed symbols) addition of spermidine (4 mM) at day 1. Data represent means ± s.e.m. (n = 4). (c) Quantification (FACS analysis) of phosphatidylserine externalization and loss of membrane integrity (annexinV/PI costaining) as well as ROS production (DHE->Eth conversion) performed at day 20 of the experiment shown in b. Data represent means ± s.e.m. (n = 4; *P 0.001).",
    "ncbi_link": "iki3: 851100
sas3: 852228"
  },
  {
    "caption": "(g) Relative change of ATG7, ATG11 and ATG15 mRNA levels by spermidine supplementation (normalised to controls) after ten days of chronological ageing as determined by reverse transcriptase real-time PCR. Data represent means ± s.e.m. (n = 3; *P 0.05 and **P 0.01).",
    "ncbi_link": "ATG11: 856162
ATG15: 850432
ATG7: 856576"
  },
  {
    "caption": "(h) Relative histone H3 Lys 18 acetylation of indicated promoter regions normalized to the acetylation of ATG7 promoter (pATG7) determined by chromatin immunoprecipitation with H3-K18Ac specific antibody and subsequent quantification of precipitated promoter DNA using quantitative real time PCR. Signals specific for indicated promoter regions were initially compared with non-immunoprecipitated samples and afterwards normalized to the pATG7 signals. Data represent means ± s.e.m. (n = 3). The P value was calculated using a two-factor ANOVA with promoter and condition (treated and non-treated) as independent factors.",
    "ncbi_link": "ATG7: "
  },
  {
    "caption": "(a) Fluorescence microscopy of wild-type yeast cells expressing an EGFP-Atg8p fusion protein with or without (control) treatment of 4 mM spermidine for 48 h. White arrows indicate vacuolar localization of EGFP-Atg8p indicative of autophagy. Scale bars, 5 μm.",
    "ncbi_link": "Atg8p: 852200"
  },
  {
    "caption": "(b) Relative alkaline phosphatase activity (ALP activity) indicative of autophagy during chronological ageing of pho8ΔC60 yeast with (open bars) or without (closed bars) application of spermidine (4 mM). Data represent means ± s.e.m. (n = 3 *; P 0.01 and **P 0.001).",
    "ncbi_link": "pho8: 852092"
  },
  {
    "caption": "(c) Relative alkaline phosphatase activity (ALP activity) indicative of autophagy during chronological ageing of wild-type (closed bars) and Δiki3Δsas3 (open bars) cells. Data represent means ± s.e.m. (n = 3; *P 0.01 and **P 0.001).",
    "ncbi_link": "iki3: 851100
sas3: 852228"
  },
  {
    "caption": "(d) Chronological ageing of wild-type (▪, o) and Δatg7 (▴, ▿) with (open symbols) or without (closed symbols) addition of spermidine (4 mM) at day 1. Data represent means ± s.e.m. (n = 4).",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(e) Chronological ageing on water of wild-type (▪, o) and Δatg7 (▴, ▿) with (open symbols) or without (closed symbols) addition of spermidine (8 mM) at day 0. Data represent means ± s.e.m. (n = 4).",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(f) Quantification (fluorescence reader) of ROS production (DHE→Eth conversion) by wild-type and Δatg7 cells with and without supplementation of spermidine (8 mM), obtained from the ageing experiment shown in panel e. Data represent means ± s.e.m. (n = 4; *P 0.07 and **P 0.01).",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(a) Fluorescence microscopy of Hoechst-counterstained HeLa cells transiently transfected with LC3-GFP subjected to 100 μM spermidine for 6 h. Representative pictures are shown. (b) Percentage of adherent cells exhibiting a clear LC3-GFP relocalization into cytoplasmic vacuoles. Numbers were determined using micrographs of Hoechst-counterstained HeLa cells as representatively shown in a. Data represent means ± s.d. (n = 3).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(e, f) Survival of Drosophila during ageing without (control) and with supplementation of food at various concentrations of spermidine (as indicated). Autophagy-deficient flies (f) homozygous mutant for Atg7 (Δatg7) were compared with flies capable of autophagy (e) and heterozygous for Atg7 (control). For details of strains and additional wild-type controls, see Supplementary Information Methods and Fig. S6h, i.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(g) Fluorescence microscopy of C. elegans transgenic embryos expressing a full-length plgg-1DsRED::LGG-1 fusion protein indicative of autophagic activity. Shown are two representative pictures of embryos untreated (control) or treated with spermidine (0.2 mM) supplementation of food. (h) Quantification of autophagic activity through measurement of DsRED::LGG-1 pixel intensity from images of wild-type animals shown in g, and bec-1 RNAi knockdown animals (bec-1 RNAi). Data represent means ± s.e.m. (n = 3) with at least 25 images processed for each trial.",
    "ncbi_link": "bec-1: 177345
lgg-1: 174050"
  },
  {
    "caption": "(i) Survival of C. elegans during ageing with and without (control) supplementation of food (UV-killed E. coli) with spermidine (0.2 mM). Wild-type (N2) animals were compared with bec-1 RNAi animals deficient in autophagy induction. For mean life spans see Supplementary Information, Table S3.",
    "ncbi_link": "bec-1: 177345"
  },
  {
    "caption": "(E) Relative percentage of TNTs in cells containing α-synucleinfibrils untransfected (control) or transfected with Myosin 10 (Myosin 10). Overexpression of Myosin 10 in the donor cell population led to an increase in the number of TNTs.",
    "ncbi_link": "Myosin 10: 17909"
  },
  {
    "caption": "(F) Quantification of the average number of ATTO-550α-synucleinfibrils per acceptor cell after 24 hours co-culture with donor cells containing α-synucleinfibrils untransfected (control) or transfected with Myosin 10 (Myosin 10). Note that Myosin 10 overexpression increases both the transfer of DiIvesicles and the number of transferred α-synuclein puncta in acceptor cells; n = 3 independent experiments (**, p < 0.01 by two-tailed Mann Whitney test).",
    "ncbi_link": "Myosin 10: 17909"
  },
  {
    "caption": "(B) The ratio of unique histone iCLIP-seq read population to unique histone RNA-seq read population was calculated and shown, with the unique histone RNA-seq read population set as "1". Error bars represent standard deviations from three replicates of ALYREF iCLIP data. Statistical analysis was performed using Student's t-test. ***P< 0.001.",
    "ncbi_link": "histone: 653604///8370///317772///440689///85235///8968///8970///8294///8329///3009///3024///3013///3017///8359///8355///8354///8353///8352///8350///8338///8336///8335///8334///8332///8331///8330///8362///8366///8364///8363///8365///8368///8367///8348///8347///8340///8341///8342///333932///85236///3008///8351///8339///8356///3006///8345///8358///8337///8349///8969///3012///8357///121504///8290///128312///92815
histone: 653604///8370///317772///440689///85235///8968///8970///8294///8329///3009///3024///3013///3017///8359///8355///8354///8353///8352///8350///8338///8336///8335///8334///8332///8331///8330///8362///8366///8364///8363///8365///8368///8367///8348///8347///8340///8341///8342///333932///85236///3008///8351///8339///8356///8345///3006///8358///8337///8349///8357///8969///3012///8290///121504///128312///92815
histone: 653604///8370///317772///440689///85235///8968///8970///8294///8329///3009///3024///3013///3017///8359///8355///8354///8353///8352///8350///8338///8336///8335///8334///8332///8331///8330///8362///8366///8364///8363///8365///8368///8367///8348///8347///8340///8341///8342///333932///85236///3008///8351///8356///3006///8345///8358///8337///8349///8969///3012///8357///8290///121504///8339///128312///92815"
  },
  {
    "caption": "(D) The distribution of histone reads in 5' UTR, CDS and 3' UTR in rRNA-depleted nuclear RNA-seq and ALYREF-iCLIP-seq.",
    "ncbi_link": "histone: 8356///3006///8345///8358///8969///8337///8349///3012///8357"
  },
  {
    "caption": "(E) Metagene analysis of normalized ALYREF signals on histone mRNA based on iCLIP-seq data. iCLIP-seq signal at each position of an mRNA is divided by the sum of signal of the mRNA to normalize each mRNA's contribution to the plot.",
    "ncbi_link": "histone: 8356///3006///8345///8969///8349///8337///8358///8357///3012"
  },
  {
    "caption": "(G) Distribution profile of clustered ALYREF binding sites on histone mRNA 3' UTRs relative to the cleavage site (CS). The CS is set as "0" in the x axis, and the relative position to the CS is marked. The y axis shows the total occurrence of binding sites in three repeats at each nucleotide.",
    "ncbi_link": "histone: 8356///3006///8345///8337///8969///8357///3012///8349///8358"
  },
  {
    "caption": "(E) (Top) Domain schematic representation of SLBP. (Bottom) Flag IPs from RNase A-treated HeLa cell lysate individually expressing indicated Flag tagged proteins, followed by western blotting using Flag and ALYREF antibodies. 3% of input was loaded. The * indicates a band probably resulted from degradation of Flag-SLBP. The white line delineates the boundary where irrelevant lanes have been removed from the same blot",
    "ncbi_link": "Flag: 
SLBP: 7884"
  },
  {
    "caption": "(E) (Top) Domain schematic representation of SLBP. followed by western blotting using Flag and ALYREF antibodies. 3% of input was loaded. The * indicates a band probably resulted from degradation of Flag-SLBP. The white line delineates the boundary where irrelevant lanes have been removed from the same blot except that Flag IPs were carried out from HA-SLBP stable expression cells transfected with plasmids expressing ALYREF fragments.",
    "ncbi_link": "SLBP: 7884"
  },
  {
    "caption": "(G) Western blotting to examine the KD efficiency of SLBP. GAPDH was used as a loading control. The white line delineates the boundary where irrelevant lanes have been removed from the same blot",
    "ncbi_link": "SLBP: 7884"
  },
  {
    "caption": "Cntl- or SLBP-siRNA treated HeLa cells were used for IPs with IgG or the ALYREF antibody. The immunoprecipitates were subjected to western analysis (H) Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001, n.s., not significant.",
    "ncbi_link": "SLBP: 7884"
  },
  {
    "caption": "Cntl- or SLBP-siRNA treated HeLa cells were used for IPs with IgG or the ALYREF antibody. The immunoprecipitates were subjected to RT-qPCRs (I). Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001, n.s., not significant.",
    "ncbi_link": "SLBP: 7884"
  },
  {
    "caption": "(J) Metagene analysis of normalized ALYREF signals on histone mRNAs in Cntl and SLBP KD cells based on iCLIP-seq data. iCLIP-seq signal at each position of an mRNA is divided by the sum of signal of the mRNA to normalize each mRNA's contribution to the plot.",
    "ncbi_link": "histone: 8356///8345///3006///8349///8358///8969///8337///8357///3012
SLBP: 7884"
  },
  {
    "caption": "(B) List of histone genes with defective 3'-end processing detected by polyA+ and polyA- RNA-seq. PolyA+ ALYREF/Cntl shows polyA+ RNA-seq RPM ratio of each histone gene in ALYREF KD versus Cntl.",
    "ncbi_link": "ALYREF: 10189"
  },
  {
    "caption": "(E, F) RT-qPCRs to detect histone mRNA levels in the polyA+ (E) or the polyA- fraction (F) in cells treated with Cntl, ALYREF or ARS2 siRNA. The arrowhead and arrows indicate the cleavage site and primer location, respectively. The bars show the relative abundance of polyA+ forms to the actin mRNA (E) and that of polyA- forms relative to the 18S rRNA (F). Data information Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "actin: 
ALYREF: 10189
ARS2: 51593"
  },
  {
    "caption": "Western blotting to examine ALYREF protein level (G) in Flag-Cntl (eIF4A3) or siRNA-resistant Flag-ALYREF stable expression cells treated with Cntl or ALYREF siRNA. The white line delineates the boundary where irrelevant lanes have been removed from the same blot",
    "ncbi_link": "ALYREF: 10189"
  },
  {
    "caption": "RT-qPCRs to detect polyA+ histone mRNA levels (H) in Flag-Cntl (eIF4A3) or siRNA-resistant Flag-ALYREF stable expression cells treated with Cntl or ALYREF siRNA. The bars show the relative abundance of histone mRNAs to the GAPDH mRNA. Data information: Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "ALYREF: 10189
GAPDH: 2597"
  },
  {
    "caption": "Cntl or ALYREF siRNA treated Flag-Lsm11 stable expression cells were used for IPs with IgG or the Flag antibody. The immunoprecipitates were subjected western analysis (D). * indicates the antibody heavy chain.",
    "ncbi_link": "ALYREF: 10189"
  },
  {
    "caption": "Cntl or ALYREF siRNA treated Flag-Lsm11 stable expression cells were used for IPs with IgG or the Flag antibody. The immunoprecipitates were subjected to RT-qPCRs (E) * indicates the antibody heavy chain. The bars show the relative IP efficiencies of histone pre-mRNAs to U7 snRNA. Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "ALYREF: 10189
U7 snRNA: 134353"
  },
  {
    "caption": "(A) (Top) Illustration of the HIST2H2AA3 reporter construct. (Bottom) FISH to detect the distribution of the HIST2H2AA3 mRNA in HeLa cells depleted of Cntl, ALYREF, THOC2 (THO) and UAP56. DAPI staining served as a nuclear marker. N and C indicate nuclear and cytoplasmic FISH signals, respectively. N/C ratios were determined for 20 cells in each experiment. Data information: Error bars represent standard deviations from biological repeats (n=3 Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "ALYREF: 10189
UAP56: 10212
HIST2H2AA3: 8337
THO: 57187
THOC2: 57187"
  },
  {
    "caption": "(B) Distribution of the endogenous HIST2H2AA3 mRNA was detected with the transcript-specific probe in HeLa cells depleted of Cntl, ALYREF, THOC2 (THO) and UAP56. N and C indicate nuclear and cytoplasmic FISH signals, respectively. N/C ratios were calculated Data information: Error bars represent standard deviations from biological repeats (n=3 Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "ALYREF: 10189
UAP56: 10212
HIST2H2AA3: 8337
THO: 57187
THOC2: 57187"
  },
  {
    "caption": "Western analysis to examine the purities of nuclear and cytoplasmic fractions (C) in Cntl and UAP56 KD cells. MTR4 and Tubulin were used as the nuclear and cytoplasmic marker, respectively.",
    "ncbi_link": "UAP56: 10212"
  },
  {
    "caption": "RT-qPCRs to examine N/C distribution of each histone mRNA (D) in Cntl and UAP56 KD cells. Data information: Error bars represent standard deviations from biological repeats (n=3 Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "UAP56: 10212"
  },
  {
    "caption": "(F) Relative NXF1 iCLIP read populations on histone mRNAs in Cntl, ALYREF and SLBP KD cells. Data information: Error bars represent standard deviations from biological repeats n=2 Statistical analysis was performed using Student's t-test. *P < 0.05, **P < 0.01, ***P< 0.001.",
    "ncbi_link": "ALYREF: 10189
histone: 8969///8356///8349///8337///8358///8357///8345///3012///3006
SLBP: 7884"
  },
  {
    "caption": "(G) NXF1 iCLIP signals along the histone mRNA. The histone mRNA is divided into 10 fractions based on their mRNA size. Each fraction represents 10% of each histone mRNA. The tenth fractions that contains the SL is boxed by green dashed lines.",
    "ncbi_link": "histone: 8969///8356///8349///8337///8358///8357///8345///3012///3006"
  },
  {
    "caption": "(A) (Top) Illustration of the reporter constructs. The black and red lines indicate H2AA3-SL and H2AA3-SLD PCR products, respectively. The dashed line indicates the FISH probe. (Bottom) FISH to detect the distribution of the corresponding mRNA at 2 hr after injection of H2AA3-SL and H2AA3-SLD PCR products. C and N indicate cytoplasmic and nuclear FISH signals, respectively. C/N ratios were determined for 20 cells in each experiment. Data information: Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, ***P< 0.001.",
    "ncbi_link": "H2AA3: 8337"
  },
  {
    "caption": "(B) (Top) Illustration of the reporter constructs. The dashed line indicates the FISH probe. FISH to detect mRNA distribution at 24 hr after transfection of the H1C-SL-Rb (cH1C) and H1C-SLD-Rb (pH1C) constructs. C/N ratios were quantified Data information Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, ***P< 0.001.",
    "ncbi_link": "H1C: 3006"
  },
  {
    "caption": "(Top) Illustration of the reporter constructs. PCR products of cG-SL and cG-SLD were used instead. cG, β-globin cDNA. Data information: Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, ***P< 0.001.",
    "ncbi_link": "β-globin: 3043"
  },
  {
    "caption": "H1C-SL-Rb or H1C-SLD-Rb construct, together with VSV M were co-transfected into HeLa cells, followed by IPs with IgG or the ALYREF antibody at 24 hr post-transfection. The immunoprecipitates were subjected to western analysis to detect ALYREF (D)",
    "ncbi_link": "H1C: 3006"
  },
  {
    "caption": "H1C-SL-Rb or H1C-SLD-Rb construct, together with VSV M were co-transfected into HeLa cells, followed by IPs with IgG or the ALYREF antibody at 24 hr post-transfection. RT-qPCRs to detect RNAs (E). The bars in the graph shows the relative ALYREF IP efficiency, with that for the H1C-SL-Rb mRNA set as "1". Data information: Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, ***P< 0.001.",
    "ncbi_link": "H1C: 3006"
  },
  {
    "caption": "(F) H1C-SLD-Rb construct with wild-type (H1C-SLDWT-Rb) or mutant (H1C-SLDmut-Rb) U7-binding sequence, together with VSV M, was co-transfected into HeLa cells, followed by IPs with IgG or the ALYREF antibody at 24 hr post-transfection. The immunoprecipitates were subjected to western analysis (left panel) and RT-qPCRs (right panel). The bars in the right graph show the relative ALYREF IP efficiency, with that for the H1C-SLDWT-Rb mRNA set as "1". Data information: Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. *P < 0.05, ***P< 0.001.",
    "ncbi_link": "H1C: 3006"
  },
  {
    "caption": "(A) Western blotting to examine the expression levels of H2B and H4 in Cntl, ALYREF and ARS2 KD cells. GAPDH was used as a loading control. The white line delineates the boundary where irrelevant lanes have been removed from the same blot",
    "ncbi_link": "ALYREF: 10189
ARS2: 51593"
  },
  {
    "caption": "(B) Growth curve of Cntl and ALYREF KD cells. Error bars represent standard deviations from biological repeats (n=3). Statistical analysis was performed using Student's t-test. **P < 0.01.",
    "ncbi_link": "ALYREF: 10189"
  },
  {
    "caption": "(C) Cell cycle analysis of Cntl, ALYREF and ARS2 KD cells. Quantifications of cells in G0/G1 (1N), G2 (2N) and S-phase (intermediate) of the cell cycle are shown in the upper right corner of each histogram.",
    "ncbi_link": "ALYREF: 10189
ARS2: 51593"
  },
  {
    "caption": "A. DIC images of abnormal embryo sacs in cycb1 mutant combinations. Red arrowheads indicate the visible nuclei in Col-0 embryo sacs (central and egg cells) and the corresponding structures in the quadruple cycb1;1-/- cycb1;2+/- cycb1;3+/- cyb1;4- mutant. Scale bars: 20 μm. B. Quantification of the different abnormal embryo sac structures in cycb1 mutant combinations (n = 202-459 embryo sacs per genotype). Different letters indicate significant differences in the proportion of abnormal embryo sacs in a Chi-squared test followed by the Marascuilo procedure to identify significant pairwise comparisons. WT = wildtype.",
    "ncbi_link": "cycb1;2: 818444
cycb1;1: 829904
cycb1;3: 820325
cyb1;4: 817217"
  },
  {
    "caption": "C. DIC images of embryo sacs 3 DAP with wildtype pollen (female x male). Red arrowheads indicate the visible embryo sac nuclei in the crosses with the quadruple cycb1;1-/- cycb1;2+/- cycb1;3+/- cyb1;4- mutant as a female donor, while the control Col-0 x Col-0 cross exhibits a developing embryo. Scale bars: 20 μm. D. Quantification of seed abortion in different cycb1 mutant combinations. Graph represents the average seed abortion rate per plant ± SD of three biological replicates, n = 463-579 seeds analyzed per genotype. Asterisks indicate significant differences in seed abortion rate in an ordinary one-way ANOVA test, followed by a Dunnett's multiple comparisons test (**** P < 0.0001).",
    "ncbi_link": "cycb1;2: 818444
cycb1;1: 829904
cycb1;3: 820325
cyb1;4: 817217"
  },
  {
    "caption": "A, B. DAPI staining of pollen in cycb1 mutants, including pollen configurations found in cycb1;1-/- cycb1;2+/- cycb1;3+/- cycb1;4-/- mutants (B). Scale bars: 5 μm. C. Quantification of DAPI-stained pollen configurations in different cycb1 mutant combinations, n = 420-616 pollen grains per genotype. Different letters indicate significant differences in the proportion of abnormal pollen (uni- and bicellular) in a Chi-squared test followed by the Marascuilo procedure to identify significant pairwise comparisons.",
    "ncbi_link": "cycb1;2: 818444
cycb1;1: 829904
cycb1;3: 820325
cycb1;4: 817217"
  },
  {
    "caption": "D. Time-lapse of confocal microscope pictures of root meristematic cells tagged with GFP-GIP1 in Col-0 (top panel) and cycb1;1 cycb1;2 (bottom panel). GIP1 localizes at the nuclear polar caps, followed by co-localization with microtubules at the spindle and phragmoplast arrays. In cycb1;1 cycb1;2 double mutants, GIP1 exhibited an abnormal localization, being found at the spindle (magenta arrowheads) and phragmoplast (white arrowheads) midzones, which are normally devoid of the protein. Scale bars: 5 μm.",
    "ncbi_link": "cycb1;2: 818444
cycb1;1: 829904"
  },
  {
    "caption": "(A) BMDMs  were treated with E. coli  (MOI=100) for 30 minutes and further cultured for various length of time  as indicated. The dynamic of ENT3  expression was determined by measuring Slc29a3  transcripts via RT-qPCR. (B) Phagocytosis inhibitor, Cytochalasin D (CytoD), pretreated BMDMs  were incubated with E. coli (MOI=100) and subjected for Slc29a3  expression analysis via RT-qPCR  6 hours post-infection. Data information: The expression level was calculated relative to Rpl19  and normalized to untreated group as 1. The results shown are combined from three biological replicates (n=3), unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Rpl19: 19921
Slc29a3: 71279
ENT3: 71279"
  },
  {
    "caption": "(D) Different bacterial components were applied as stimulants to BMDMs. Slc29a3  expression was analyzed after 30 minutes of stimulation and a total of 6 hours incubation. (E) BMDMs  were treated with different doses of LPS  for 30 minutes, harvested 6 hours post-stimulation, and subjected for RT-qPCR  analysis. Data information: The expression level was calculated relative to Rpl19  and normalized to untreated group as 1. The results shown are combined from three biological replicates (n=3), unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Rpl19: 19921
Slc29a3: 71279"
  },
  {
    "caption": "(C) WT or (D) MyD88-/- BMDMs  were stimulated with 10 ng/ml LPS  or live  E. coli  (MOI=100) in the presence of 10 µM TBK  inhibitor, MRT 67307, and analyzed for Slc29a3 expression. Data information: The results shown are combined from three biological replicates (n=3), unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "MyD88: 17874
Slc29a3: 71279"
  },
  {
    "caption": "(E) The 10 ng/ml LPS-treated BMDMs  were examined for Ifnb1 expression  after 30 minutes of stimulation and a total of 6 hours incubation. Data information: The results shown are combined from three biological replicates (n=3), unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "(F) BMDMs  were treated with 100 U/ml of IFN-β  for various length of time  and subjected for Slc29a3 expression. Data information: The results shown are combined from three biological replicates (n=3), unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Slc29a3: 71279"
  },
  {
    "caption": "(B-E) BMDMs  from WT, IFNAR1-/- (B), or STAT1-/- (C) mice  were treated with 10 ng/ml LPS, live E. coli (MOI=100), or 100 U/ml IFN-β, harvested and examined for Slc29a3  induction. BMDMs  from WT, IFNAR1-/- (D) or STAT1-/- (E) mice  were treated with 100 U/ml  IFN-β, 50 µg/ml poly(I:C), or EMCV  (MOI=10), harvested and examined for Slc29a3  induction. Data information: The expression  level was calculated relative to Rpl19  and normalized to untreated group as 1. The results shown in B to E are from three biological replicates (n=3) Unpaired two-tailed Student's t-test was used for statistical analysis, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "IFNAR1: 15975
Rpl19: 19921
Slc29a3: 71279
STAT1: 20846"
  },
  {
    "caption": "(F-H) The expression  dynamic of Slc29a3  was profiled in BMDMs  treated with two different doses of IFN-α (F),  IFN-β (G), IFN-γ (H) for various length of time  as indicated. Data information: The expression  level was calculated relative to Rpl19  and normalized to untreated group as 1. The results shown in F to H from two biological replicates (n=2). Unpaired two-tailed Student's t-test was used for statistical analysis, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Rpl19: 19921
Slc29a3: 71279"
  },
  {
    "caption": "(A) The induction fold change (treated/untreated) of Slc29a3  and selected ISG transcripts were curated from INTERFEROME database. Shown is data extracted from 250 IU/ml  IFN-β  treated BMDMs. Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Slc29a3: 71279"
  },
  {
    "caption": "(A-C) (A) BMDMs  were infected with EMCV  (MOI=10) and harvested at indicated time points. (B) THP-1 derived macrophages  were challenged with EV71  (MOI=5) and collected at different time points. (C) BMDMs  were co-cultured with 50 µg/ml  poly (I:C)  with various length of time  and harvested. The mRNA expression  of Slc29a3  or SLC29A3  was measured by RT-qPCR. The expression level was calculated relative to Rpl19  or RPLP0  and normalized to untreated group at time  0 as 1. Results are combined from three biological replicates (n=3) Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "Rpl19: 19921
RPLP0: 6175
Slc29a3: 71279
SLC29A3: 55315"
  },
  {
    "caption": "(D, E) ENT3fl/fl and Cx3cr1cre/+ENT3fl/fl mice  (n=12) were challenged with EMCV  (104 PFU, i.p.) and monitored for the survival (D) and disease severity (E) for two weeks. Survival  results were analyzed by log-rank (Mantel-Cox) test, *p < 0.05. Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "cre: 2777477
Cx3cr1: 13051
ENT3: 71279"
  },
  {
    "caption": "(F, G) ENT3fl/fl and  Cx3cr1cre/+ENT3fl/fl mice  were challenged with 107 PFU EMCV  and measured the viral titer in the brain  at post-infection  day 3 by plaque assay (n=6). Shown are representative  plaque assay  images (F) and the quantification (G). Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "cre: 2777477
Cx3cr1: 13051
ENT3: 71279"
  },
  {
    "caption": "(A) WT and ENT3-/- BMDMs  were infected with EMCV  (MOI=10), and the culture supernatants were harvested 24 hours post-infection to measure the production of IFN-α,  IFN-β, and  IFN-γ by ELISA. Shown are combined results from three biological replicates (n=3). Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, ***p < 0.001. n.s. no significance. The combined data are shown as mean ± SEM.",
    "ncbi_link": "ENT3: 71279"
  },
  {
    "caption": "(D, E) The mitochondrial  respiratory capacity (D) and glycolysis capacity (E) of WT and ENT3-/- BMDMs  treated with 1000 U/ml IFN-β for 6 hours were measured by  extracellular flux analysis. Shown are the representative results of OCR  and ECAR  kinetics from six biological replicates (n=6). Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, ***p < 0.001. n.s. no significance. The combined data are shown as mean ± SEM.",
    "ncbi_link": "ENT3: 71279"
  },
  {
    "caption": "(G, H) The replication of EMCV  in WT (G) and ENT3-/- BMDMs (H) were evaluated in the presence of exogenous 1 or 10 µM of ribonucleosides  (A, U, C, G) 9 hours post-infection  (MOI=10). The expression of EMCV-2A2B   was determined by RT-qPCR. Shown are results from three to four biological replicates (n=3-4). Data information: In G, H) the EMCV-2A2B  expression level was calculated relative to Rpl19  and normalized to untreated group at time  0 as 1. Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, ***p < 0.001. n.s. no significance. The combined data are shown as mean ± SEM.",
    "ncbi_link": "2A: 
2B: 
Rpl19: 19921
ENT3: 71279"
  },
  {
    "caption": "(A) Illustration of strategy to track the viral uncoating upon infection. (B-D) (B) WT and ENT3-/- BMDMs  were infected with Syto82-labeled EMCV  (MOI=1) and subjected to  live imagining 30, 60 and 90 minutes post-infection. The arrowheads indicated the Syto82+ virus puncta in the cell. Scale bars represent 10 µm. (C) Quantification of Syto82  signal in BMDMs  after 60 minutes was performed by enumerating Syto82+ cells (%) and (D) the mean fluorescent intensity (MFI) per Syto82+ cell (D). Results were generated from images of three biological replicates (n=3), each with 4 fields analyzed. Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "ENT3: 71279"
  },
  {
    "caption": "(E) WT and ENT3-/- BMDMs  were infected with Syto82-labeled EMCV  (MOI=1) and co-stained  with 100 nM Lysotracker Green, subjected to live imagining 60 minutes post-infection. Data were the representative images of two biological replicates (n=2). Scale bars represent 5 µm. (F) WT and ENT3-/- BMDMs   were infected with EMCV  (MOI=10) for 2 hours and then enriched the endosomes  and lysosomes. EMCV  particles in endosome- or lysosome-enriched fractions were quantified by  plaque assay. Shown are combined results from three biological replicates (n=3). Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "ENT3: 71279"
  },
  {
    "caption": "(G-K) (G) Calu-3  cells were infected with  SARS-CoV-2  original strain or delta  variant at MOI=0.1 for 48 hours, harvested, and examined for SLC29A3  induction. (H) ENT3  knockdown in Calu-3  cells was performed by lentiviral  shRNA system. The knockdown efficiency was confirmed by RT-qPCR. ENT3  knockdown Calu-3 cells were infected with SARS-CoV-2 delta  variant and subjected for the viral replication analysis  24 hours post-infection. The virus released out of cells was measured by plaque assay (I), and the viral titer in the cells was measured by RT-qPCR (J). (K) The replication of SARS-CoV-2 delta  variant in scramble and ENT3  knockdown  Calu-3 cells were evaluated in the presence of exogenous 1 or 10 µM of ribonucleosides  (A, U, C, G) 24 hours post-infection  (MOI=0.1). The SLC29A3  expression level was calculated relative to RPLP0  and normalized to control as 1. The SARS-CoV-2 E gene expression level was calculated relative to RPLP0  to normalize the cell number. Shown are combined results from three biological replicates (n=3). Data information: Unpaired two-tailed Student's t-test was used for statistical analysis, *p < 0.05, **p < 0.01, ***p < 0.001, n.s. no significance. Data are shown as mean ± SEM.",
    "ncbi_link": "E gene: 43740570
RPLP0: 6175
SLC29A3: 55315
ENT3: 55315"
  },
  {
    "caption": "B Top, diagram of ASOs tested below, mapped to their position of complementarity on ApoER2. Bottom, RT-PCR of RNA isolated from HeLa cells transfected with the indicated ASO at a final concentration of 80 nM. RNA spliced forms are labeled. Quantification of the percentage inclusion is shown below the image and calculated as: Inclusion (%)=[exon 19 included/(exon 19 included+exon 19 skipped)] x 100.",
    "ncbi_link": "ApoER2: 7804"
  },
  {
    "caption": "D Top, RT-PCR analysis of ApoER2 exon 19 splicing in HeLa cells depleted of SRSF1 using an SRSF1-specific siRNA. Control is a non-specific siRNA. Bottom, Immunoblot analysis of SRSF1 from HeLa lysates depleted of SRSF1. β-actin is included as a control.E Quantification of exon 19 splicing in (D). Error bars show s.e.m. P-value was determined using Student's two-tailed t-test.",
    "ncbi_link": "ApoER2: 7804
SRSF1: 6426"
  },
  {
    "caption": "F Top, RT-PCR analysis of exon 19 splicing in a primary mouse kidney cell line depleted of SRSF1 by RNAi. Control is a non-specific siRNA. Bottom, Immunoblot analysis of SRSF1 from HeLa lysates depleted of SRSF1. β-actin is included as a control.G Quantification of exon 19 splicing in E. Error bars show s.e.m. P-value was calculated using Student's two-tailed t-test.",
    "ncbi_link": "SRSF1: 110809
SRSF1: 6426"
  },
  {
    "caption": "A Top, ASOs mapped onto the mouse ApoER2 exon 19 gene region. Bottom, RT-PCR of RNA isolated from mouse cells transfected with different ASOs. Quantification of percent exon 19 inclusion is shown below the gel image.",
    "ncbi_link": "ApoER2: 16975"
  },
  {
    "caption": "D RT-PCR analysis of RNA isolated from the hippocampus of mice treated as adults by ICV injection of indicated ASOs. C refers to a non-specific control ASO.E Quantitation of ApoER2 exon 19 inclusion from D (mean s.e.m., one-way ANOVA with Bonferroni multiple comparison test.",
    "ncbi_link": "ApoER2: 16975"
  },
  {
    "caption": "A RT-PCR analysis of ApoER2 exon 19 splicing in RNA isolated from hippocampus of 4 month old AD and WT mice treated with ASO-21 or ASO-C at P1-2.B Quantitation of exon 19 splicing. (mean s.e.m.; Kruskal-Wallis test with Dunn's multiple comparison test.",
    "ncbi_link": "ApoER2: 16975"
  },
  {
    "caption": "C Immunoblot for exon 19 containing ApoER2 (top) and total ApoER2 (bottom). β-actin was used as loading control.D Quantification of ApoER2 protein isoforms shown in C (mean s.e.m., student's t-test).",
    "ncbi_link": "ApoER2: 16975"
  },
  {
    "caption": "(b) Immuno-gold EM micrographs of HeLa cells transfected with GFP-PLD1 and subjected to 1 h of nutrient deprivation in the presence (St+B) or absence (St) of bafilomycin (50 nM). Insets denote high magnification of the selected area. Scale bar, 500 nm. Right panel: Histogram showing morphometric analysis of the relative distribution of GFP-PLD1-positive gold particles on the outer (arrows) and inner (arrowheads) membranes of the autophagosomal-like structures. Values denote means±s.e.m. (n=14). **P0.01.",
    "ncbi_link": "PLD1: 5337"
  },
  {
    "caption": "(a) Confocal analysis of HeLa cells subjected to nutrient deprivation for 2 h. Cells were transfected with HA-PLD1 and GFP-ATG14L (upper panels) or with HA-PLD1 alone (lower panels). Upper panels: HA-PLD1 (red), GFP-ATG14L (green), endogenous LC3 (blue). Lower panels: HA-PLD1 (green), endogenous ATG16L (red) and LC3 (blue). Insets show high magnification of the selected areas. The triple insets on the right indicate high magnification of the selected areas for two channels in various combinations. Scale bar, 5 μm.",
    "ncbi_link": "ATG14L: 22863
PLD1: 5337"
  },
  {
    "caption": "(c) EM analysis showing that GFP-PLD1 does not localize to the isolation membrane (arrows) in cells expressing the strawberry-ATG4-C74A mutant. Immuno-gold EM micrographs of HeLa cells transfected with GFP-PLD1 and pStrawberry-ATG4-C74A and subjected to 1 h of nutrient deprivation. Inset denotes high magnification of the selected area. Scale bar, 250 nm.",
    "ncbi_link": "ATG4: 23192
PLD1: 5337"
  },
  {
    "caption": "(b) Western blot analysis of HA-PLD1 and endogenous LC3 levels in post-nuclear supernatant (PNS, upper panel), as well as in cytosolic/soluble (S) and particulate (P) fractions prepared from PNS after high-speed centrifugation (middle panel). GAPDH was used as loading control in PNS fractions. HeLa cells were transfected with expression vectors encoding HA-PLD1 for 24 h and subjected to 2 h of nutrient deprivation in the presence or absence of the PI3K inhibitor wortmannin (100 nM). Lower panel: quantitative analysis of HA-PLD1 immunoreactivity expressed as P/S ratio. Conditions were as follows: normal medium (Nm); normal medium with wortmannin (Nm+W); starvation condition (St); starvation condition+wortmannin (St+W). Values denote means±s.e.m. (n=3).",
    "ncbi_link": "PLD1: 5337"
  },
  {
    "caption": "(a) Western blot analysis showing the effects of siRNA-mediated Vps34 (siVps34) downregulation on the expression levels of HA-PLD1 and Vps34 compared with control cells (siCtrl). Cells were incubated in normal medium (Nm) or subjected to 2 h of nutrient deprivation in the presence of 50 nM bafilomycin (St+B). HeLa cells were transfected for 48 h with siRNA directed to Vps34 (siVps34) or a control sequence (siCtrl) and then transfected for 24 h with a plasmid encoding HA-PLD1.",
    "ncbi_link": "Vps34: 5289
PLD1: 5337"
  },
  {
    "caption": "(b) Confocal imaging showing the effects of Vps34 (siVps34) downregulation on HA-PLD1 (green), endogenous LC3 (blue) and Lamp1 (red) on 2 h of nutrient deprivation compared with control treatment (siCtrl). Scale bar, 5 μm. (c) Confocal analysis showing the subcellular localization of HA-PLD1 mutated in its PX domain (F120A/R179Q), so as to abolish phosphoinositide binding (HA-PXmut). HeLa cells were transiently transfected with a plasmid encoding HA-PXmut and fixed after 2 h of nutrient deprivation. HA-PXmut (green), endogenous LC3 (blue) and Lamp1 (red). Scale bar, 10 μm. In b and c, insets show high magnification of the selected areas. The triple insets on the right indicate high magnification of the selected areas for two channels in various combinations.",
    "ncbi_link": "Vps34: 5289
PLD1: 5337"
  },
  {
    "caption": "(c) Immunostaining of endogenous LC3 in Pld1 WT and KO MEFs showing a reduced number and size of the LC3-positive compartment in KO MEFs. The DAPI staining is shown in blue. Cells were deprived of nutrients for 2 h in the absence (St, upper panels) or presence of bafilomycin (St+B, lower panels). Scale bar, 5 μm. (d) Quantification of the average size (top panel) and number of LC3-positive compartments per cell (bottom panel) in Pld1 WT and KO MEFs starved for 2 h. Values denote means±s.e.m. (n=6, number of cells=26-45 for all the conditions). **P0.01; *P0.05.",
    "ncbi_link": "Pld1: 18805"
  },
  {
    "caption": "(a) Immunofluorescent detection of endogenous LC3 (red) in liver sections from fed or starved Pld1 WT and KO mice. Sections were counterstained with DAPI. Scale bar, 5 μm. (b) Quantitative analysis of endogenous LC3 immunofluorescence in liver sections derived from fed or starved Pld1 WT and KO mice. Histograms show the average number, size and surface area of LC3-positive compartments. Values denote means±s.e.m. ((n=25-28), 4 mice per genotype). **P0.01.",
    "ncbi_link": "Pld1: 18805"
  },
  {
    "caption": "(c) Electron microscopic analysis showing a reduction in the size and number of autophagosome/amphisome-like structures (AP) in PLD1-deficient mice after food restriction. Representative electron micrographs from animals analysed in a showing APs (arrows) and autophagolysosomes/lysosomes (AL, arrowheads) in liver sections from starved WT and KO mice. Insets show high magnification of the selected areas. Scale bar, 1 μm. (d) Morphometric analysis of the number (per 100 μm2 cytoplasmic area) and relative surface area (% cytoplasmic area) of APs and ALs. Values denote means±s.e.m. (n=36 electron micrograms, from a total of 3,600 μm2 cytoplasmic area per genotype). **P0.01. (c) Morphometric analysis of the diameter of APs and ALs in the liver of PLD1-deficient mice after food restriction. Values denote means±s.e.m. (n=60). **P0.01.",
    "ncbi_link": "PLD1: 5337"
  },
  {
    "caption": "(D) FIBCD1 expression  in various human   visceral tissues and brain  regions (inset). Expression  is plotted relative to the tissue with lowest detectable expression  (trachea; inset, choroid plexus). n represents technical replicates (n = 2).",
    "ncbi_link": "FIBCD1: 84929"
  },
  {
    "caption": "(A) Immunofluorescent  images of control and neuronal  (Nsyb) CG10359  (dFibcd1) RNAi-mediated knockdown D. melanogaster, 3rd instar larvae NMJ  (NMJ6/7) stained  with anti-horseradish peroxidase  antibodies. Empty control and RNAi-mediated knockdown of CG10359  (dFibcd1-i) lines #1, 2 and 3 shown. Scale bar = 20µm. Representative images of 3 independent experiments. Quantification of (A), control and CG10359  knockdown lines NMJ neuron bouton  number (B) n(empty) = 12; n(line #1) = 20; n(line #2) = 11; n(line #3) = 14. Data information: each data point represents an individual NMJ  Data is represented as mean and error bars represent SEM. p values were calculated using 2-way ANOVA (panels B * = p≤0.05; ** =p≤0.01; *** =p≤0.001; **** p≤0.0001.",
    "ncbi_link": "CG10359: 38434
Fibcd1: 38434
syb: 36080"
  },
  {
    "caption": "(E) Representative coronal section images of Golgi-Cox staining  of Fibcd1  WT and KO hippocampi  (left), Neurolucida tracing of  hippocampal CA1 pyramidal neurons (middle) and apical dendrites with spines  (right). Scale bars as indicated.",
    "ncbi_link": "Fibcd1: 98970"
  },
  {
    "caption": "(B) Immunoblot  analysis (left) and quantification of signal intensity (right) of Fibcd1  WT (blue) versus Fibcd1  KO littermates (red) adult hippocampi  with antibodies against CS-0S, CS-4S, CS-6S and actin  as a loading control. Each lane represents an independent animal (n = 3). Protein marker sizes are indicated. Data information: For panel B, each data point represent hippocampal  protein isolates from an individual mouse, Data are shown as mean values +/- SEM. p values were calculated using paired Student's t-test (panels B * = p≤0.05; ** =p≤0.01; *** =p≤0.001; **** p≤0.0001.",
    "ncbi_link": "Fibcd1: 98970"
  },
  {
    "caption": "(F) Confocal  images depicting internalisation  of FITC-tagged CS-4S  by FIBCD1-overexpressing HEK293T  lines compared to untransduced cells and unstained cells. Left, representative images; right, quantification. Data is plotted as total puncta per condition (n = 5). Cells are further stained  with CellMask Orange (cellular membrane) and Hoechst  (nuclei). Scale bar = 50µm. Data information: for panels F, each data point represents an individual cell preparation. Data are shown as mean values +/- SEM. p values were calculated using 1-way ANOVA (panels F, * = p≤0.05; ** =p≤0.01; *** =p≤0.001; **** p≤0.0001.",
    "ncbi_link": "FIBCD1: 84929"
  },
  {
    "caption": "(A) Left, representative image of immunofluorescent staining  (MAP2, red; DAPI, blue) of primary hippocampal  cultures at 2 days in vitro (DIV), plated on +/- CSPG  coating with and without prior digestion with ChABC, as indicated. Right, quantification of DIV2 images, showing the number of protruding cells per field normalised to untreated condition. n(Fibcd1  WT) = 4; n(Fibcd1  KO) = 3. Scale bar = 250µm. (B) Left, representative images of DIV14 neurons, same conditions as in (A). Right, quantification of DIV14 images, representing the percentage of cells per field that are clumped. n(Fibcd1  WT) = 3; n(Fibcd1  KO) = 2. Scale bar = 250µm. Data information: For panels A and B each data point represents an individual preparations of primary cell culture. Data are represented as mean and error bars represent SEM. p values were calculated by 1-way ANOVA. * = p≤0.05; ** =p≤0.01; *** =p≤0.001.",
    "ncbi_link": "Fibcd1: 98970"
  },
  {
    "caption": "A αSMA mRNA levels in TGFβ-treated HFL1 fibroblasts and the effect of the IRE1α inhibitor 4μ8C. *P = 0,001.",
    "ncbi_link": "αSMA: 59"
  },
  {
    "caption": "B Collagen1α2 mRNA levels in TGFβ-treated HFL1 fibroblasts ± the IRE1α inhibitor 4μ8C. *P = 0,01.",
    "ncbi_link": "Collagen1α2: 1278"
  },
  {
    "caption": "C mRNA levels of ER-stress related genes in TGFβ-treated HFL1 fibroblasts. *P CHOP = 0,045, *P Bip = 0,023, *P spliced XBP-1 P = 0,001, compared to corresponding control.",
    "ncbi_link": "CHOP: 1649
Bip: 3309
XBP-1: 7494"
  },
  {
    "caption": "E Agarose gel showing the presence of spliced and unspliced XBP-1 mRNA in TGFβ-treated HFL1 fibroblasts ± the IRE1α inhibitor 4μ8C.",
    "ncbi_link": "XBP-1: 7494"
  },
  {
    "caption": "H αSMA mRNA expression in TGFβ-treated HFL1 cells overexpressing two RNase dead mutants (K599A and K907A) of IRE1α. *P K599A = 0.013, *P K907A = 0.0008 compared to WT.",
    "ncbi_link": "αSMA: 59
IRE1α: 2081"
  },
  {
    "caption": "I αSMA mRNA expression in TGFβ-treated IRE1α -/- or WT MEF cells. *P = 0.025.",
    "ncbi_link": "αSMA: 11475
IRE1α: 78943"
  },
  {
    "caption": "A miR-150 levels in TGFβ-treated HFL1 fibroblasts and the effect of the IRE1α inhibitor 4μ8C. * P = 0.046 compared to control.",
    "ncbi_link": "miR-150: 406942"
  },
  {
    "caption": "B miR-150 levels in HFL1 fibroblasts overexpressing two RNase dead mutants (K599A and K907A) of IRE1α. * P = 0.0043 (K599A), P = 0.043 (K907A), compared to control.",
    "ncbi_link": "IRE1α: 2081
miR-150: 406942"
  },
  {
    "caption": "C miR-150 levels in TGFβ-treated WT (IRE1α +/+) and IRE1α -/- MEF cells. *P = 0.018. Results are expressed as fold change compared to the Ctrl.",
    "ncbi_link": "IRE1α: 78943
miR-150: 387168"
  },
  {
    "caption": "D miR-150 levels in IRE1α -/- MEF cells that were either untransfected (UT) or transfected with miRNA inhibitor control (siCtrl) or with a miR-150-5p miRNA inhibitor. * P = 0.034 compared to UT.",
    "ncbi_link": "IRE1α: 78943
miR-150: 387168"
  },
  {
    "caption": "E αSMA mRNA expression in TGFβ-treated IRE1α -/- MEF cells that were either untransfected (UT) or transfected with miRNA inhibitor control (siCtrl) or with a miR150-5p miRNA inhibitor. *P = 0.043 compared to UT.",
    "ncbi_link": "αSMA: 11475
IRE1α: 78943
miR150: 387168"
  },
  {
    "caption": "F miR-150 levels in HFL1 fibroblasts transfected with a control plasmid (Ctrl) or a miR-150 expression plasmid (miR150). * P = 0.038.",
    "ncbi_link": "miR-150: 406942
miR150: 406942"
  },
  {
    "caption": "G Western blot of c-Myb in TGFβ-treated HFL1 fibroblasts that were either untransfected (UT), transfected with a control plasmid (pCtrl) or a miR150 expression plasmid (miR150). *P = 0.0206 in UT Ctrl vs. UT TGFβ and P = 0.0126 in pCtrl Ctrl vs. pCtrl TGFβ .",
    "ncbi_link": "miR150: 406942"
  },
  {
    "caption": "I c-Myb mRNA levels in untransfected HFL1 cells (UT) and in cells transfected with a control siRNA (siCtrl) or an siRNA targeting c-Myb (sicMyb). * P = 0.00001 compared to UT.",
    "ncbi_link": "c-Myb: 4602"
  },
  {
    "caption": "J αSMA mRNA expression in untransfected HFL1 cells (UT) and in cells transfected with a control siRNA (siCtrl) or with a siRNA targeting c-Myb (sicMyb). * P = 0.0042 in UT Ctrl vs. UT TGFβ.",
    "ncbi_link": "αSMA: 59
c-Myb: 4602"
  },
  {
    "caption": "L In vitro cleavage assay with recombinant IRE1α and miR-150 (left) or XBP-1 (right).",
    "ncbi_link": "miR-150: 406942"
  },
  {
    "caption": "M miR-150 expression in HFL-1 cells that were pre-treated with TGFβ in the absence of presence of 4μ8C and then treated with Actinomycin D (ActD) for 4 and 24 hours. * P = 0.027 compared to TGFβ.",
    "ncbi_link": "miR-150: 406942"
  },
  {
    "caption": "A Analysis of ER size in HFL1 fibroblasts treated with TGFβ in the absence (Ctrl) or presence of the IRE1α inhibitor 4μ8C, or in HFL1 cells transfected with a siRNA control siRNA (siCtrl) or with siRNA targeting XBP-1 (siXBP-1). The ER was visualized with ER tracker Red and nuclei stained with Hoechst (left, scale bars = 20 μm) or by electron microscopy (right, scale bars = 200 nm) where red lines mark the ER.B Quantification of ER size relative to the nucleus from the experimental setup in A. * P = 0.0001 in Ctrl, and * P = 0.0223 in siCtrl.",
    "ncbi_link": "XBP-1: 7494"
  },
  {
    "caption": "C XBP-1 mRNA expression in untransfected HFL1 cells (UT) and in cells transfected with control siRNA (siCtrl) or siRNA targeting XBP-1 (siXBP-1). * P = 0,0001.",
    "ncbi_link": "XBP-1: 7494"
  },
  {
    "caption": "E BiP mRNA expression in liver tissue from mice presented in A. * P = 0,020.",
    "ncbi_link": "BiP: 14828"
  },
  {
    "caption": "F Representative gel showing levels of spliced and unspliced XBP-1 in liver tissue from control and CCl4-induced cirrhotic mice and the effect of 4μ8C treatment.",
    "ncbi_link": "XBP-1: 22433"
  },
  {
    "caption": "G miR150 expression in liver tissue from mice in A. * P = 0,032 compared to untreated controls.",
    "ncbi_link": "miR150: 387168"
  },
  {
    "caption": "H αSMA mRNA levels in primary stellate cells isolated from mouse liver and then treated or not with TGFβ ± 4μ8C. * P = 0,031, n = 3.",
    "ncbi_link": "αSMA: 11475"
  },
  {
    "caption": "I BiP mRNA levels in primary stellate cells isolated from mouse liver and then treated with or without TGFβ ± 4μ8C. * P = 0,008, n = 3.",
    "ncbi_link": "BiP: 14828"
  },
  {
    "caption": "L Quantification of mRNA expression levels of CTGF and collagen in primary human hepatic stellate cells stimulated with TGFβ ±4μ8C.",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "D Representative image of the area selected for laser capture microdissection (scale bars = 100 μm).E Expression levels of αSMA mRNA in samples of hypodermis obtained by laser capture microdissection. Ctrl (n = 5), Ctrl + 4μ8C (n = 5), TGFβ (n = 5), TGFβ + 4μ8C (n = 5). * P = 0,044.F miR-150 expression levels in the same samples as shown in E.",
    "ncbi_link": "αSMA: 11475
miR-150: 387168"
  },
  {
    "caption": "H αSMA mRNA expression in primary mouse skin fibroblasts after treatment with TGFβ ± 4μ8C. * P = 0,049, n = 4.",
    "ncbi_link": "αSMA: 11475"
  },
  {
    "caption": "I Agarose gel showing levels of spliced and unspliced XBP-1 in primary mouse skin fibroblasts treated as indicated with TGFβ and 4μ8C.",
    "ncbi_link": "XBP-1: 22433"
  },
  {
    "caption": "J BiP mRNA expression in primary mouse skin fibroblasts after treatment with TGFβ in the absence and presence of 4μ8C. * P = 0,00007 for TGFβ vs. Ctrl and P = 0,00002 for TGFβ vs. TGFβ + 4μ8C. n=4.",
    "ncbi_link": "BiP: 14828"
  },
  {
    "caption": "L miR-150 mRNA levels in primary mouse skin fibroblasts treated as indicated with TGFβ and 4μ8C. * P = 0,00031 compared to untreated control, n = 3.",
    "ncbi_link": "miR-150: 387168"
  },
  {
    "caption": "A CTGF mRNA expression levels in skin (dSSc) and lung (LSSc) fibroblasts isolated from scleroderma patients and treated with the IRE1α inhibitor 4μ8C. * P = 0,018 for dSSc (n = 6) and P = 0,003 for LSSc (n = 3).",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "B Collagen1α2 mRNA expression levels in the same samples as in A. * P = 0,0030 for dSSC and P = 0,0036 for LSSc.",
    "ncbi_link": "Collagen1α2: 1278"
  },
  {
    "caption": "E mRNA levels of αSMA in primary lung fibroblasts isolated from patients with either cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) or asthma. * P = 0,00001 for asthma vs. healthy controls, and P = 0,00003 for ctrl vs. 4μ8C in asthma patients.",
    "ncbi_link": "αSMA: 59"
  },
  {
    "caption": "F Quantification of mRNA levels for BiP in same samples as in E. * P = 0,0023 between asthma and healthy controls and P = 0,0031 between 4μ8C-treated and control treatment in fibroblasts from asthma patients.",
    "ncbi_link": "BiP: 3309"
  },
  {
    "caption": "(B) Flow cytometry  analysis of WT to Il21r-/- splenic  SWHEL B cells over time. (C) WT to Il21r-/- SWHEL B cell ratio within CTV  division peaks. Data information: Data in (B) is representative of 8-9 biological replicates (n = 8-9) pooled from two independent experiments with statistical analysis by one-way ANOVA with Tukey's post-test. ** p ≤ 0.01; **** p ≤ 0.0001. Data show concatenated data from 4-5 biological replicates (n = 4-5) and are representative for two independent experiments.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "(B) Flow cytometry  analysis showing WT to Il21r-/- SWHEL B cell  ratio of cells that have been in S phase and thus incorporated BrdU. Data information: Data are representative of 5-7 biological replicates (n = 5-7) from two independent experiments. Statistical analysis by one-sample t test. *p ≤ 0.05.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "(D) Ratio of the proportion of BrdU  positive WT and Il21r-/- SWHEL B cells with 2N DNA  content 4, 10 and 12 hours post BrdU  pulse on day 3.5 post immunization. Data information: Data are representative of 5-7 biological replicates (n = 5-7) from two independent experiments. Statistical analysis by one-sample t test. *p ≤ 0.05.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "(C) Rate of de novo  cell cycle entry 10 hours post in vivo IL-21 (2 µg) or saline  pulse. The ratio of WT to Il21r-/- cells not in S/G2 at the time of pulse (BrdU- cells) and containing >2N DNA  content 10 hours after pulse is shown. Data information: Data are representative of 10-12 biological replicates (n = 10-12) from two independent experiments. Statistical analysis by one-sample t test. * p ≤ 0.05.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "Phosphoflow analysis  of naïve WT or Il21r-/- B cells following in vitro culture for 3 hours with or without IL-21 (20 ng/mL) and/or in the presence of BCR  cross-linking (biotinylated anti-Igκ  + anti-Igλ  and avidin-mediated cross-linking) or agonistic anti-CD40. (A) Exemplary p-AKT  (S473) staining  and (B) quantification of p-AKT  median fluorescence intensity (MedFI). (C) Exemplary p-S6  (Ser235/236) staining  and (D) quantification of frequency of p-S6  positive cells Data information: Data are representative of 4 biological replicates (n = 4). Statistical analysis by one-way ANOVA with Tukey's post-test (D), t test (B, E) * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "(B, C) Analysis of splenic  OTII  Tfh  cells by flow cytometry. (B) Tfh cell count  and (C) Proportion of Il21Gfp/+ OTII Tfh   cells transcribing the Il21  locus and thus expressing GFP. Data information: Data are representative of 5-6 biological replicates (n = 5-6) form two independent experiments. Statistical analysis by one-way ANOVA with Tukey's post-test (B, C). * p ≤ 0.05; ** p ≤ 0.01.",
    "ncbi_link": "GFP: 
Il21: 60505"
  },
  {
    "caption": "Analysis of splenic  WT and Il21r-/- SWHEL B cells  by  flow cytometry. (D) CTV  profile of and (E) absolute  cell count in pooled CTV  division peaks (0-4, 5-8, 9-11+). Data information: Data are representative of 5-6 biological replicates (n = 5-6) form two independent experiments. D, show concatenated data representative of 3-5 biological replicates. Data in E were analyzed after log transformation using Multiple paired t tests and p values corrected for multiple comparisons using Holm-Šídák method. * p ≤ 0.05; ** p ≤ 0.01.",
    "ncbi_link": "Il21r: 60504"
  },
  {
    "caption": "(A-E) Analysis of splenic  SWHEL B cells and PC  by  flow cytometry. (A) Proportion of SWHEL B cells with a FAS+GL7+ GC  phenotype, (B) SWHEL GC B cell count and (C) representation of  IL-21R deficient cells among total SWHEL GC B cells. (D) CD98+ CD138+_SWHEL PC count and (E) representation of IL-21R  deficient cells among total SWHEL PC. Data information: Data are representative of 6-10 biological replicates (n = 6-10) from two independent experiments. Data in B, D were analyzed after log transformation with with statistical analysis by Multiple paired t tests (A, B, D) and p-values corrected for multiple comparisons using Holm-Šídák method or One-way ANOVA with Tukey's post-test (C) or t test (E).",
    "ncbi_link": "IL-21R : 60504
IL-21R: 60504"
  },
  {
    "caption": "WB SecA with additional mutations (WT, Y794G, R342E) was added to preformed intermediates (IM) and incubated for the indicated times before proteolysis. The gel is representative of two replicates.   Quantification of (B). Points show IM band intensities normalized to the 0-min time point for each replicate. Lines show average of replicates. Colors correspond to WB SecA carrying additional mutations, as shown in the inset box.   ",
    "ncbi_link": "SecA: 944821"
  },
  {
    "caption": "Imidazole (imi) and either WT or mutant SecA were added to translocation intermediates (IM) pre-formed with SecA dN20::H6. The samples were incubated for the indicated times before proteolysis with proteinase K (Prot. K). The gel is representative of two replicates, except for the experiment with the R792G/K797G mutant and the 30-min time points. Quantification of (B). Points show IM band intensities normalized to the 0-min time point for each replicate. Lines show average of replicates. Colors correspond to different SecA mutants as shown in the inset box. As in (B), but ATPγS was added together with imidazole. The gel is representative of two replicates. Quantification of (E) as in (C). As in (D), but DTT was added with ATPγS ten minutes after the addition of imidazole and WT or mutant SecA. The gel is representative of two replicates.   Quantification of (G) as in (F), except that both the intensities of the IM (darker colors) and FL (lighter colors) bands were measured.   ",
    "ncbi_link": "SecA: 944821"
  },
  {
    "caption": "A. Arginine methylase inhibitor decreases SIRT7 methylation. HEK293T cells expressing Flag-tagged SIRT7 were treated with increasing doses of AdOx as indicated for 24 hrs. After immunoprecipitated with Flag-beads, SIRT7 was analyzed by western blot and detected by an antibody against mono-methylarginine (α-me1). Relative methylation ratio (Ratio) was calculated by normalizing arginine methylation level against the Flag-SIRT7 protein. WCL, whole cell lysate",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "C. PRMT inhibitor reduces arginine methylation of wildtype SIRT7, but not its RK/RF mutants. HEK293T cells expressing wildtype SIRT7 or its RK/RF mutants were treated with or without AdOx for 24 hrs. Arginine methylation of immunopurified SIRT7 was determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "D. SIRT7 is mono- and asymmetrically di-methylated at R388. Flag-tagged SIRT7 and its RK/RF mutants were expressed in HEK293T cells. Immunopurified SIRT7 was blotted with antibodies against mono-methylarginine (α-me1), asymmetric di-methylarginine (α-me2a), and symmetric di-methylarginine (α-me2s), respectively",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "H. SIRT7 is methylated at R388. HEK293T cells ectopically expressing Flag-tagged SIRT7 were treated with increasing concentrations of AdOx for 24 hrs as indicated. SIRT7 protein was pulled down by Flag-beads. Arginine methylation of SIRT7 was detected with a site-specific antibody against R388 methylation [α-meSIRT7(R388)]",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "B. Co-expression of PRMT6, but not PRMT1 or PRMT3, increases R388 methylation of SIRT7. Flag-tagged SIRT7 and GFP-tagged PRMT1, PRMT3, or PRMT6 were co-expressed in HEK293T cells. R388 methylation of immunopurified SIRT7 was analyzed by western blot",
    "ncbi_link": "PRMT3: 
PRMT1: 3276
PRMT6: 55170
SIRT7: 51547"
  },
  {
    "caption": "C. Wildtype PRMT6, but not its catalytic-deficient mutant, upregulates SIRT7 R388 methylation. Wildtype PRMT6 or its V86K/D88A mutant (DM) was co-expressed with Flag-tagged SIRT7 in HEK293T cells. R388 methylation of immunopurified SIRT7 was detected by western blot",
    "ncbi_link": "PRMT6: 55170
SIRT7: 51547"
  },
  {
    "caption": "D-E. PRMT6 physically interacts with endogenous SIRT7. Endogenous SIRT7 (D) or PRMT6 (E) was pulled down using corresponding antibody from HEK293T, MEF, and primary mouse hepatocytes, respectively. Input and immunoprecipitates were analyzed by western blot",
    "ncbi_link": "PRMT6: 55170
PRMT6: 99890
SIRT7: 51547
SIRT7: 209011"
  },
  {
    "caption": "G. PRMT6 inhibitor reduces arginine methylation of wildtype SIRT7, but not RK/RF mutants. Wildtype SIRT7 or its RK/RF mutants were stably expressed in MEF cells. After treating cells with or without PRMT6-specific chemical inhibitor (PRMT6i) for 24 hrs, SIRT7 was immunoprecipitated and blotted with R388-specific methylation antibody",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "H. Prmt6 depletion decreases R388 methylation of endogenous Sirt7. Scramble control cells (scr) or MEF cells stably expressing two different shRNAs (#1 and #2) against Prmt6 was established. R388 methylation of immunopurified endogenous Sirt7 was determined by western blot",
    "ncbi_link": "Prmt6: 99890"
  },
  {
    "caption": "J-K. Prmt6 depletion reduces the percentage of R388-methylated endogenous SIRT7 in MEF cells. R388-methylated endogenous SIRT7 was captured from scramble control cells (scr) and Prmt6-knockdown MEF cells by using R388 site-specific methylation antibody (J). Input, output, and immunoprecipitate were analyzed by western blot to quantify the percentage of R388-methylated protein (K) (mean±SD, n=3 experimental replicates)",
    "ncbi_link": "Prmt6: 99890"
  },
  {
    "caption": "A. RF, but not RK mutant, suppresses H3K18 deacetylase activity of SIRT7. Flag-SIRT7 and its RK/RF mutants were expressed in HEK293T and MEF cells, respectively. Cell lysates were subjected to western blot to detect histone H3K18 acetylation. H3K27ac and H3K56ac were included as negative control. The level of each histone acetylation marker was normalized against histone H3 (Ratio)",
    "ncbi_link": "SIRT7: 51547
SIRT7: 209011"
  },
  {
    "caption": "B. R388 methylation of SIRT7 decreases its H3K18 deacetylase activity. HEK293T cells expressing wildtype SIRT7 or its RK/RF mutants were treated with or without AdOx for 24 hrs. The SIRT7 enzyme was immunopurified with Flag-beads and further incubated with extracted chromatin in vitro. R388 methylation of immunopurified SIRT7 and H3K18ac of in vitro deacetylated chromatin were determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "C. RF, but not RK mutant, shows reduced H3K18 deacetylase activity in vitro. Chromatin was extracted from HEK293T cells and incubated with recombinant GST-tagged SIRT7 (wildtype and RK/RF mutants) in vitro for 2 hrs. H3K18ac was determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "D. Wildtype PRMT6, but not its methylase-dead mutant, decreases the H3K18 deacetylase activity of SIRT7. Flag-tagged SIRT7 was co-expressed with wildtype PRMT6 or its catalytic-inactive mutant (DM) in HEK293T cells. The H3K18 deacetylase activity of immunopurified SIRT7 was assayed in vitro",
    "ncbi_link": "PRMT6: 55170
SIRT7: 51547"
  },
  {
    "caption": "E. PRMT6 deficiency promotes the H3K18 deacetylase activity of SIRT7. Control sgRNA or two independent sgRNAs (#1 and #2) against PRMT6 was introduced into HEK293T cells. Flag-tagged SIRT7 was ectopically expressed in these cells. The histone deacetylase activity of immunoprecipitated SIRT7 was assayed in vitro using chromatin as a substrate. R388 methylation of immunopurified SIRT7 and H3K18 acetylation level of in vitro deacetylated chromatin was determined by western blot",
    "ncbi_link": "PRMT6: 55170
SIRT7: 51547"
  },
  {
    "caption": "Wildtype SIRT7 or its RF mutant was re-expressed in Sirt7-knockdown MEF cells (A)",
    "ncbi_link": "SIRT7: 209011
Sirt7: 209011"
  },
  {
    "caption": "Wildtype SIRT7, but not its RF mutant, restores mitochondria mas in Sirt7-deficient MEF cells Mitochondria mass was determined by Mito Tracker Red staining (B) (mean ± SD, n=3 experimental replicates, *p<0.05; **p<0.01; n.s.=not significant, unpaired two-tailed t test)",
    "ncbi_link": "SIRT7: 209011
Sirt7: 209011"
  },
  {
    "caption": "Wildtype SIRT7, but not its RF mutant, restore ATP leve in Sirt7-deficient MEF cells Cellular ATP was quantified and normalized to cell number (C) (mean ± SD, n=3 experimental replicates, *p<0.05; **p<0.01; n.s.=not significant, unpaired two-tailed t test)",
    "ncbi_link": "SIRT7: 209011
Sirt7: 209011"
  },
  {
    "caption": "Wildtype SIRT7, but not its RF mutant, restore cellular respiration in Sirt7-deficient MEF cells Respiration flux was determined as indicated (D). (mean ± SD, n=3 experimental replicates, *p<0.05; **p<0.01; n.s.=not significant unpaired two-tailed t test)",
    "ncbi_link": "SIRT7: 209011
Sirt7: 209011"
  },
  {
    "caption": "Wildtype SIRT7, but not its RF mutant, downregulates SIRT7 target genes involved in mitochondria biogenesis. Wildtype SIRT7 and its RF mutant were stably expressed in MEF cells (E)",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "Wildtype SIRT7, but not its RF mutant, downregulates SIRT7 target genes involved in mitochondria biogenesis SIRT7 target gene expression was determined and presented as a heatmap on a log2 scale (F)",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "Control cells and stable Sirt7-knockdown MEF cells were treated with or without 5 µM PRMT6i for 24 hrs. The H3K18ac level at the promoter of SIRT7 target genes (Gfm2, Mrps31, Mrps33, and Mrpl40) was determined by ChIP-qPCR, Rabbit IgG was used as a negative control (G) ( Data shown are mean±SD, n=3 experimental replicates, *p<0.05; **p<0.01; ***p < 0.001; n.s.=not significant, unpaired two-tailed t test",
    "ncbi_link": "Gfm2: 320806
Mrpl40: 18100
Mrps31: 57312
Mrps33: 14548
Sirt7: 209011"
  },
  {
    "caption": "Inhibition of Prmt6 decreases mitochondria mas of control cells, but not Sirt7-knockdown MEF cells Control cells and stable Sirt7-knockdown MEF cells were treated with or without 5 µM PRMT6i for 24 hrs Mitochondria mass was determined by Mito Tracker Red staining (H) ( Data shown are mean±SD, n=3 experimental replicates, *p<0.05; **p<0.01; ***p < 0.001; n.s.=not significant, unpaired two-tailed t test",
    "ncbi_link": "Prmt6: 99890
Sirt7: 209011"
  },
  {
    "caption": "Inhibition of Prmt6 decrease ATP leve of control cells, but not Sirt7-knockdown MEF cells. Control cells and stable Sirt7-knockdown MEF cells were treated with or without 5 µM PRMT6i for 24 hrs Cellular ATP was quantified and normalized to cell number (I) ( Data shown are mean±SD, n=3 experimental replicates, *p<0.05; **p<0.01; ***p < 0.001; n.s.=not significant, unpaired two-tailed t test",
    "ncbi_link": "Prmt6: 99890
Sirt7: 209011"
  },
  {
    "caption": "Inhibition of Prmt6 decrease the respiration flux of control cells, but not Sirt7-knockdown MEF cells. Control cells and stable Sirt7-knockdown MEF cells were treated with or without 5 µM PRMT6i for 24 hrs Respiration flux was determined as indicated (J). ( Data shown are mean±SD, n=3 experimental replicates, *p<0.05; **p<0.01; ***p < 0.001; n.s.=not significant, unpaired two-tailed t test",
    "ncbi_link": "Prmt6: 99890
Sirt7: 209011"
  },
  {
    "caption": "A. Glucose depletion reduces SIRT7 methylation. MEF cells stably expressing Flag-SIRT7 were cultured in medium depleted with glucose (12 hrs), FBS (12 hrs) or glutamine (24 hrs). R388 methylation of immunopurified SIRT7 and Ampk phosphorylation were determined by western blot. R388 methylation level was normalized to Flag-SIRT7 (Ratio)",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "B. Glucose starvation decreases R388 methylation of SIRT7 in a time-dependent manner. MEF cells stably expressing Flag-SIRT7 were cultured in glucose-free media as indicated. R388 methylation level of immunopurified SIRT7 was determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "C. Glucose dose-dependently upregulates R388 methylation of SIRT7. MEF cells stably expressing Flag-SIRT7 were cultured with increasing concentrations of glucose as indicated for 12 hrs. R388 methylation of SIRT7 and Ampk phosphorylation were determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "D. AICAR treatment decreases R388 methylation of SIRT7. MEF cells stably expressing Flag-SIRT7 were treated with or without AICAR for 12 hrs. R388 methylation of immunoprecipitated SIRT7 was determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "G. AMPK deletion increases SIRT7 R388 methylation. Flag-tagged SIRT7 was stably expressed in Ampk wildtype (WT) and Ampk α1/α2 double-knockout (DKO) MEF cells and 293A cells. SIRT7 protein was immunopurified with Flag-beads, R388 methylation was determined by western blot",
    "ncbi_link": "Ampk: 105787
SIRT7: 51547"
  },
  {
    "caption": "H. AMPK is required for glucose starvation-induced R388 hypomethylation of SIRT7. Ampk wildtype (WT) and Ampk α1/α2 double-knockout (DKO) MEF cells stably expressing Flag-SIRT7 were cultured with or without glucose for 12 hrs. SIRT7 was purified with Flag-beads and R388 methylation was determined by western blot",
    "ncbi_link": "Ampk: 105787
SIRT7: 51547"
  },
  {
    "caption": "I. PRMT6 is necessary for AMPK-induced SIRT7 hypomethylation. Flag-tagged SIRT7 was stably expressed in scramble control MEF cells or cells expressing two independent shRNAs targeting Prmt6 (#1 and #2). Cells were cultured with or without glucose for 12 hrs. R388 methylation of immunopurified SIRT7 was determined by western blot",
    "ncbi_link": "PRMT6: 99890
Prmt6: 99890
SIRT7: 51547"
  },
  {
    "caption": "J. PRMT6 is necessary for AMPK-induced SIRT7 hypomethylation. Wildtype MEFs and Ampk DKO cells were treated with PRMT6i for 24 hrs. SIRT7 was purified by Flag-beads, and R388 methylation of SIRT7 was determined by western blot",
    "ncbi_link": "Ampk: 105787"
  },
  {
    "caption": "L. R388 methylation of SIRT7 does not modulate its phosphorylation. MEF cells stably expressing Flag-tagged wildtype SIRT7 or RK mutant were treated with PRMT6i (24 hrs) and cultured with or without glucose (12 hrs) as indicated. SIRT7 protein was immunopurified with Flag-beads, R388 methylation and phosphorylation of SIRT7 were determined by western blot",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs. R388 methylation of SIRT7 was determined by western blot (C) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test",
    "ncbi_link": "SIRT7: 209011
SIRT7: 51547"
  },
  {
    "caption": "AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs H3K18ac level at SIRT7-target gene promoters were determined by ChIP-qPCR. Normal rabbit IgG was used as a negative control (D) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test",
    "ncbi_link": "SIRT7: 209011
SIRT7: 51547"
  },
  {
    "caption": "AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs mRNA expression was determined by qPCR analysis (E) (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test",
    "ncbi_link": "SIRT7: 209011
SIRT7: 51547"
  },
  {
    "caption": "AICAR and PRMT6 inhibitor decrease R388 methylation and epigenetically downregulate SIRT7-target genes. MEF cells stably expressing Flag-SIRT7 were incubated with or without PRMT6i for 12 hrs, followed by treatment with 1 mM AICAR for 12 hrs Mitochondria mass was determined by Mito Tracker Red staining (F). (Data shown are mean±SD, n=3 experimental replicates, **p<0.01; ***p < 0.001, unpaired two-tailed t test",
    "ncbi_link": "SIRT7: 209011
SIRT7: 51547"
  },
  {
    "caption": "Cardiac glycogen content in 17 weeks old male Vegfb+/+ (n=6), Vegfb+/- (n=6) and Vegfb-/- mice (n=5) presented as mean ± SEM. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: * <0.05 (compared to Vegfb+/+).",
    "ncbi_link": "Vegfb: 22340"
  },
  {
    "caption": "Relative mRNA expression of the Slc2a glucose transporter (GLUT) family members (1-13) in cardiac ECs derived from Vegfb+/+ (n=4) and Vegfb-/- (n=4) mice. Data represent normalized PLIER values (mean ± SEM) from microarray analysis performed on n=4+4 RNA samples (one RNA sample/mouse).",
    "ncbi_link": "Vegfb: 22340"
  },
  {
    "caption": "mRNA expression levels of the SLC2A transporter (GLUT) family members (1-14) in HUVECs. Data presented as mean ± StDev relative to RPL19 expression from 3 independent experiments.",
    "ncbi_link": "RPL19: "
  },
  {
    "caption": "mRNA expression levels of VEGFB, SLC2A1, NRP1 and FLT1 (VEGFR1) in HUVECs. Data presented as mean ± StDev relative to RPL19 expression from 3 independent experiments.",
    "ncbi_link": "RPL19: 
FLT1: 2321
VEGFR1: 2321
NRP1: 8829
SLC2A1: 6513
VEGFB: 7423"
  },
  {
    "caption": "2-NBD-glucose uptake in response to 2 h treatment with VEGF-B186 (B186) in HUVECs exhibiting siRNA-mediated knock-down of FLT1, NRP1, SCL2A1, KDR (VEGFR2) or control siRNA. Data presented as mean ± SEM from three individual experiments. Statistical evaluation using one-way ANOVA and Sidak´s multiple comparisons test, p-value: * <0.05 (comparisons made to respective untreated control).",
    "ncbi_link": "FLT1: 2321
KDR: 3791
VEGFR2: 3791
NRP1: 8829
SCL2A1: 6513"
  },
  {
    "caption": "mRNA expression analysis from enriched cardiac endothelial cells (open columns, n=4 mice) or whole heart (closed columns, n= 3 mice). Data presented as mean ± StDev relative to Rpl19 expression. Enrichment factor is calculated as mean cardiac EC/mean whole heart and presented in the box.",
    "ncbi_link": "Rpl19: "
  },
  {
    "caption": "mRNA expression analysis of lipoprotein receptors in HUVECs. Data presented as mean ± StDev relative to RPL19 expression from 3 independent experiments.",
    "ncbi_link": "RPL19: "
  },
  {
    "caption": "Cellular cholesterol content in HUVECs treated with control siRNA or siRNA targeting LDLR or Scavenger receptor B1 (SCARB1, SRBI) followed by 15 min stimulation with VEGF-B186. Data presented as mean ± SEM from representative experiments performed in triplicates. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: * <0.05, ** <0.01, *** <0.001 (compared to respective control).",
    "ncbi_link": "LDLR: 3949
SCARB1: 949
Scavenger receptor B1: 949
SRBI: 949"
  },
  {
    "caption": "glucose uptake (C) in HUVECs treated with control siRNA or siRNA targeting LDLR or Scavenger receptor B1 (SCARB1, SRBI) followed by 15 min stimulation with VEGF-B186. Data presented as mean ± SEM from representative experiments performed in triplicates. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: * <0.05, ** <0.01, *** <0.001 (compared to respective control).",
    "ncbi_link": "LDLR: 3949
SCARB1: 949
Scavenger receptor B1: 949
SRBI: 949"
  },
  {
    "caption": "Cellular cholesterol content of ECs freshly isolated from Ldlr+/+ and Ldlr-/- mice stimulated for 15 min with VEGF-B186. Data presented as mean ± SEM from a representative experiment performed in triplicates. Statistical evaluation using one-way ANOVA and Tukey´s multiple comparisons test, p-value: *** <0.001 (compared to Ldlr+/+ control).",
    "ncbi_link": "Ldlr: 16835"
  },
  {
    "caption": "Quantification of non-esterified cholesterol content by means of filipin staining in the blood vessel compartment (podocalyxin+) in hearts of 15-week old male C57BL/6 Vegfb+/- (n=5) and Vegfb-/- mice (n=7), normalized to wildtype (Vegfb+/+) mice (n=8). Data presented as box-and-whisker plots. Boxes represents lower/upper quartiles with the median values indicated with a horizontal line. Whiskers represent min-max values. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: * <0.05, ** <0.01 (compared to Vegfb+/+ mice).",
    "ncbi_link": "Vegfb: 22340"
  },
  {
    "caption": "Quantification of non-esterified cholesterol content by means of filipin staining in hearts of 15-week old male C57BL/6 Vegfb+/- (n=5) and Vegfb-/- (n=7) mice, normalized to wildtype (Vegfb+/+) mice (n=8). Data presented as box-and-whisker plots. Boxes represents lower/upper quartiles with the median values indicated with a horizontal line. Whiskers represent min-max values. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: ** <0.01 (compared to Vegfb+/+ mice).",
    "ncbi_link": "Vegfb: 22340"
  },
  {
    "caption": "Quantification of non-esterified cholesterol content by means of filipin staining in hearts of 25-week old male CD1 Flt1+/lacz (n=20) mice, normalized to wildtype CD1 (Flt1+/+) mice (n=16). Data presented as box-and-whisker plots. Boxes represents lower/upper quartiles with the median values indicated with a horizontal line. Whiskers represent min-max values. Statistical evaluation using t-test, p-value: ** <0.01.",
    "ncbi_link": "lacz: 
Flt1: 14254"
  },
  {
    "caption": "Quantification of non-esterified cholesterol content by means of filipin staining in hearts of 12 to 16-week old male C57BL/6 wildtype (Vegfb+/+) (n=4), BKS.C57BL/6 db/+ Vegfb+/+ (n=8), db/db Vegfb+/- (n=10) and db/db Vegfb-/- (n=4) mice, normalized to db/db Vegfb+/+ (n=6) mice. Data presented as box-and-whisker plots. Boxes represents lower/upper quartiles with the median values indicated with a horizontal line. Whiskers represent min-max values. Statistical evaluation using one-way ANOVA and Dunnett´s multiple comparisons test, p-value: * <0.05, *** <0.001 (compared to db/db Vegfb+/+ mice).",
    "ncbi_link": "db: 16847
Vegfb: 22340"
  },
  {
    "caption": "Phenotypic analysis. Wild-type, uvr8, and rup1 rup2 seedlings were grown in 1/2 MS with or without UV-B (1 W/m2) for 2 weeks. Images are shown in (A); scale bars = 5 mm.",
    "ncbi_link": "rup1: 835301
rup2: 832438
uvr8: 836506"
  },
  {
    "caption": "Phenotypic analysis. Wild-type, uvr8, and rup1 rup2 seedlings were grown in 1/2 MS with or without UV-B (1 W/m2) for 2 weeks. The lateral root density (number of lateral roots/length of primary root) (B) and average length of lateral roots (each plant) (C) of the indicated genotypes were measured. SDs (n > 8 independent seedlings) are indicated.",
    "ncbi_link": "rup1: 835301
rup2: 832438
uvr8: 836506"
  },
  {
    "caption": "GUS staining of seedlings expressing DR5p::GUS transgene in the WT, uvr8 and rup1 rup2 background. Seedlings were grown in 1/2 MS with or without UV-B for 2 weeks. Images of lateral root primordia (E) and lateral roots (F) are shown. Scale bars = 100 and 50 μm, respectively.",
    "ncbi_link": "GUS: 
rup1: 835301
rup2: 832438
uvr8: 836506"
  },
  {
    "caption": "UV-B inhibits the response of Arabidopsis seedlings to exogenously added NAA in a UVR8-dependent manner, since the response to NAA was not repressed in uvr8. Seedlings of the indicated genotypes were grown in LD (16-h light/ 8-h dark) conditions for 5 days, then transplanted to new plates containing 0.4 μM NAA and kept in continuous white light or white light plus UV-B (1 W/m2) for 7 days. Images are shown in (C); scale bars = 2 mm. The lateral root density (number of lateral roots/length of primary root) (D) and average length of lateral roots (E) of the indicated genotypes were measured.",
    "ncbi_link": "uvr8: 836506"
  },
  {
    "caption": "Phenotypic analysis. WT, GR-UVR8R338A/uvr8 and GR-UVR8W285F/uvr8 seedlings were grown in LD (16-h light/ 8-h dark) for 5 days, then transplanted to new medium with 0.4 μM NAA and with or without 20 μM DEX and kept in white light plus UV-B (1 W/m2) for 7 days. Images are shown in (A); scale bars = 2 mm. The lateral root density (number of lateral roots/length of primary root) (B) and average length of lateral roots (C) of indicated genotypes were measured. SDs (n > 8) are indicated.",
    "ncbi_link": "GR: 824631
uvr8: 836506
UVR8: 836506"
  },
  {
    "caption": "UVR8 inhibited auxin responses under UV-B in a tissue-autonomous way. WT and uvr8 seedlings grown in LD for 5 days were used for reciprocal grafting. Seedlings were kept in LD for 7 days after grafting, then transplanted to new medium containing 0.4 μM NAA and kept in UV-B light (1 W/m2) for 10 days. Images are shown in (D); scale bar = 2 mm. The lateral root density (number of lateral roots/length of primary root) (E) and average length of lateral roots (F) of indicated genotypes were measured. SDs (n > 8) are indicated.",
    "ncbi_link": "uvr8: 836506"
  },
  {
    "caption": "Transcriptome analysis of gene expression regulated by auxin, UV-B, and UVR8. (A) Heat map of UV-B-, UVR8-, and auxin-regulated genes. The parameter measured by color key shows the Log-fold change. (B) Auxin signaling genes are up-regulated by auxin treatment but down-regulated by UV-B in a UVR8-dependent manner. Three biological replicates were analyzed and final Log fold-change is shown.",
    "ncbi_link": "UVR8: 836506"
  },
  {
    "caption": "Quantitative RT-PCR analysis of auxin signaling gene expression in wild-type (Col-0), uvr8, and rup1 rup2 seedlings. Seedlings grown in continuous white light for 5 days were kept in white light (D) or transferred to white light plus UV-B (E) for 1 day with the addition of 1 μM IAA. Error bars are SD of three biological replicates.",
    "ncbi_link": "rup1: 835301
rup2: 832438
uvr8: 836506"
  },
  {
    "caption": "qPCR analysis of auxin signaling gene expression in roots of WT, uvr8, and rup1 rup2 seedlings. Seedlings grown in continuous white light for 12 days were kept in white light (F) or transferred to white light plus UV-B (G) for 1 day with the addition of 0.4 μM NAA. Error bars are SD of three biological replicates.",
    "ncbi_link": "rup1: 835301
rup2: 832438
uvr8: 836506"
  },
  {
    "caption": "BiFC assay showing that UVR8 interacts with MYB73/MYB77 in white light condition. N. benthamiana was co-transformed with MYB73-nYFP/MYB77-nYFP and cCFP, nYFP, and UVR8-cCFP, or MYB73-nYFP/MYB77-nYFP and UVR8-cCFP. BF, bright field. Merge, overlay of the YFP and bright field images. Scale bar = 20 μm.",
    "ncbi_link": "CFP: 
YFP: 
MYB73: 829880
MYB77: 824168
UVR8: 836506"
  },
  {
    "caption": "Quantitative RT-PCR analysis of auxin signaling gene expression in roots of wild type (Col-0), uvr8, myb73 myb77, and myb73 myb77 uvr8. (D) Results under white light and (E) under white plus UV-B light. Seedlings grown in continuous white light for 12 days were kept in white light or transferred to white light plus UV-B for 1 day with the addition of 0.4 μM NAA, and roots were collected to analyze auxin signaling gene expression. Error bars represent SD of three biological replicates.",
    "ncbi_link": "myb73: 829880
myb77: 824168
uvr8: 836506"
  },
  {
    "caption": "EMSA showing that MYB73/MYB77 binds to the promoter of IAA19. Cold IAA19p or IAA19mp (MBSI motif mutated) was added as a competitor.",
    "ncbi_link": "IAA19: 820793"
  },
  {
    "caption": "ChIP-qPCR analysis showed that UV-B inhibits the DNA-binding activity of MYB73. ChIP-qPCR assays were performed using transgenic seedlings expressing 35S::MYB73-TAP, treated with or without UV-B for 5 h before harvesting samples. Chromatin fragments (~500 bp) were immunoprecipitated by anti-Myc antibody, and the precipitated DNA was analyzed by qPCR using the primer pairs indicated. The IP/Input ratios are shown with SDs (n=3). ChIP-qPCR showing that UV-B inhibits the DNA-binding activity of MYB73 in a UVR8-dependent manner. The IP/Input ratios are shown with SDs (n=3).",
    "ncbi_link": "MYB73: 829880
UVR8: 836506"
  },
  {
    "caption": "ChIP-qPCR showing that UV-B inhibits the DNA-binding activity of MYB73 in roots (G) in a UVR8-dependent manner (H). The IP/Input ratios are shown with SDs (n=3).",
    "ncbi_link": "UVR8: 836506"
  },
  {
    "caption": "ChIP-qPCR showing that UV-B inhibits MYB77 from binding to the indicated promoters in a UVR8-dependent manner. The IP/Input ratios are shown with SDs (n=3).",
    "ncbi_link": "UVR8: 836506"
  },
  {
    "caption": "B. DCC and netrin-1 expression (FACS analysis) in B-cells lymphocytes isolated from DCC+/+ and DCCmut/mut mice spleen and lymph nodes. Results are presented as expression ratios between means expression levels in mutant animals (n=3) and control ones (n=3). No significant difference was observed between wild-type and mutant animals.",
    "ncbi_link": "DCC: 13176"
  },
  {
    "caption": "C. DCCmut/mut mouse with splenomegaly and systemic lymphadenopathy. Left panel: black and white arrows indicate respectively the inguinal and mesenteric lymph nodes. Right panel: enlarged spleen in a lymphoma-bearing mutant mouse (left) as compared to control organ (right).",
    "ncbi_link": "DCC: 13176"
  },
  {
    "caption": "D. Incidence of lymphoid proliferations and lymphoma in DCC+/+ (n=19) and DCCmut/mut (n=29) mice. Tumors classification was performed blinded to genotype according to anatomopathologists consensus (29). *: p=0.036; one-tailed Fisher's exact test.",
    "ncbi_link": "DCC: 13176"
  },
  {
    "caption": "E. Histology analysis and immunophenotyping of lymphoid proliferations in DCC control and mutant mice. Sections from control spleen, low-grade FL and high-grade DLBCL were stained with hematoxylin-eosin-safran or with antibodies to B220 or Ki67. w: white pulp, r: red pulp, cr: compressed red pulp.",
    "ncbi_link": "DCC: 13176"
  },
  {
    "caption": "A-B. Analysis of DCC (A) and netrin-1 (B) expression in a cohort of normal tonsils (n=9), Germinal-Center-B-Cell-like-DLBCL (n=13), Activated-B-Cell-like-DLBCL (n=18) and MCL (n=36). Quantification of genes expression was performed by Q-RT-PCR, relatively to HPRT housekeeping gene. **: p<0.005; ****: p<0.0001; two-sided Mann-Whitney U-test.",
    "ncbi_link": "HPRT: 
DCC: 1630
netrin-1: 9423"
  },
  {
    "caption": "A. Expression of netrin-1 and DCC in lymphoma cell lines. Quantification was performed by Q-RT-PCR in 21 lymphoma cell lines. HPRT housekeeping gene was used as a standardization control. Netrin-1 and DCC levels are indicated as follow: −, not detectable; + to ++++, moderate to very high expression. ABC and GC-DLBCL cell lines are highlighted respectively in blue and green, MCL ones are in grey. Expression of netrin-1 (in green) by immunofluorescence using netrin-1 antibody on OCI-Ly3 and Granta-519 cell lines is shown on the right panel. Nuclei are counterstained in blue by Hoechst.",
    "ncbi_link": "HPRT: 
DCC: 1630
netrin-1: 9423
Netrin-1: 9423"
  },
  {
    "caption": "B. Caspase-3 activity in Granta-519 cells after transfection of scrambled siRNA (si-Ctl) or netrin-1 siRNA (si-netrin-1), with or without DCC siRNA (si-DCC). Results are means+/-std of four independent experiments. $: p=0.03; *: p=0.02; two-sided Mann-Whitney U-test.",
    "ncbi_link": "DCC: 1630
netrin-1: 9423"
  },
  {
    "caption": "F. Caspase-3 activity in Granta-519 cells treated with net-1 mAb antibody or with an unrelated Ig-G1 antibody (Ctl), with or without silencing of DCC via siRNA (siDCC). Results are means+/-std of four independent experiments. $: p=0.05; *: p=0.02; two-sided Mann-Whitney U-test.",
    "ncbi_link": "DCC: 1630"
  },
  {
    "caption": "A, SW620 and HCT116 cells were treated with the indicated concentrations of SB505124 (SB) or LGK974 (LGK) for 16 h. Total cell extracts were analyzed by WB. Protein quantification was analyzed by densitometry of three different experiments and represented B, SW620 and HCT116 cells expressing a shCtl or shRor2 vectors were analyzed by WB. Quantification of the WBs from three biological replicates are presented in the right panel. Values correspond to fold variation in shRor2 versus shCtl cells (mean ± SD).",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "C, RNA was isolated from shCtl or shRor2 SW620 and HCT116 cells and the expression of the indicated genes was assessed by qRT-PCR. Values correspond to fold variation in shRor2 versus shCtl cells. Results are the mean ± SD of at least three biological replicates performed in triplicate.",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "D, SW620 and HCT116 cells expressing a shCtl or shRor2 vectors were analyzed by WB. Quantification of the WBs are presented in Appendix Fig S3D as in B.",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "G, WB analysis of HT29 M6 and SW480 overexpressing Snail1. Quantification is presented in Appendix Fig S5I.",
    "ncbi_link": "Snail1: 20613"
  },
  {
    "caption": "I, SW620 and HCT116 cells were transfected with control or Snail1 siRNA and analyzed by qRT-PCR (I, mean ± SD of three biological replicates performed in triplicate).",
    "ncbi_link": "Snail1: 6615"
  },
  {
    "caption": "A, Smad2 phosphorylation was determined in extracts from shCtl or shRor2 SW620 and HCT116 cells. The quantification is presented in the right panel (mean ± SD or three biological replicates).",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "D, MSC were treated with the conditioned media from shCtl or shRor2 SW620 , D) for the indicated times. TGFβ receptor inhibitor SB505124 (SB, 5 μM) was added when indicated in D. Cells were lysed and proteins analyzed by WB. Quantification of the protein levels from D is represented at the lower panel (mean ± SD of three biological replicates)",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "C, Representative micrographs of the effects of Ror2 depletion on HCT116 cells soft-agar colony formation (21 days) (left). Representative micrographs of SW620 cells are shown in Appendix Fig S7B. Results show the mean ± SD of the number of colonies in triplicate samples of three independent experiments (right).",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "F, RNA was isolated from SW620 control, stably-depleted of Ror2, treated with LGK974 for 16 h or transfected with siSnail1 and the expression of the stem cell gene markers LGR5, ASCL2, SMOC2 and the differentiation marker KRT20 was assessed by qRT-PCR. The figure shows the mean ± SD of at least three biological replicates (performed in triplicate) represented with respect to the corresponding control (dashed line).",
    "ncbi_link": "ASCL2: 430
KRT20: 54474
LGR5: 8549
Ror2: 4920
SMOC2: 64094
Snail1: 6615"
  },
  {
    "caption": "I, J, WB (I) and RNA analysis (J) of MTO cells infected with shRor2 or shCtl. Quantification of the WB is also presented (I, right). Results are the mean ± SD of three biological replicates (performed in triplicated in J).",
    "ncbi_link": "Ror2: 4920"
  },
  {
    "caption": "A-C, Viability was assayed by MTT in the indicated cells treated with LGK when specified and supplemented with cisplatin for 24 h. In B, cisplatin resistance was assessed in shRor2 cells transfected with a Snail1 expression plasmid or the corresponding empty plasmid. The figure shows the mean ± SD of the results of three experiments.",
    "ncbi_link": "Ror2: 4920
Snail1: 20613"
  },
  {
    "caption": "A. Retinal whole mount immunostaining  for Isolectin-B4 (red) and Desmin (green) in WT (top panel) and Glut1iECKO (bottom panel) mice  showing pericyte  coverage in the vasculature. Left and right panels show representative images with 20x or 63x magnification, respectively. B. Quantification of the pericytes  coverage in the  retinal vasculature of WT (blue) and Glut1iECKO (orange) mice. (n=9 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "C. Immunostaining  for CD31  (green), CD13  (white; pericyte  marker) and αSMA  (cyan) using paraffin  section from WT (top panel) and Glut1iECKO (bottom panel) mice.",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "D. Quantification of the pericytes  coverage using CD13 immunostaining  in the brain vasculature of WT (blue) and Glut1iECKO (orange) mice. (n=7 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.) E. Quantification of the smooth muscle cell coverage using αSMA immunostaining  in the brain vasculature of WT (blue) and Glut1iECKO (orange) mice. (n=13 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "J. Representative confocal  images of fibrin  (green), CD31  (red) and DAPI  (blue) immunostaining  in the brain vasculature of WT (top panel) and Glut1iECKO (bottom panel) mice  K. Quantification of the number of cadaverine 555 positive brain parenchyma  cells  in WT (blue) and Glut1iECKO (orange) mice. (n=13 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.) L. Quantification of extravascular fibrin  deposits in WT (blue) and Glut1iECKO (orange) mice. (n=9 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.) M. Quantification of lactate  in the cerebrospinal fluid of WT (blue) and Glut1iECKO (orange) mice. (n=3 from 3 independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "H. Representative images showing  mTFP  (cyan) and Venus (yellow) fluorescence in HBVPs  which have direct contact with control (upper panel) or GLUT1  (lower panel) siRNA treated BMECs. VECAD immunostaining  (purple) was used for endothelial staining. I. Quantification of the  mTFP/Venus  fluorescence ratio of laconic in HBVPs  which have direct contact with control (siCON) or GLUT1  (siGLUT1) siRNA-treated BMECs. (n=12 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "GLUT1: 10755"
  },
  {
    "caption": "I. Representative images showing mTFP  (cyan) and Venus  (yellow) fluorescence in HBVPs  which have direct contact with control (upper panel) or MCT1  (lower panel) siRNA-treated BMECs. VECAD immunostaining  was used for endothelial staining. J. Quantification of the  mTFP/Venus  fluorescence ratio of laconic  in HBVPs  which have direct contact with control (siCON) or MCT1  (siMCT1) siRNA-treated BMECs. (n=8 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "MCT1: 6566"
  },
  {
    "caption": "K. Representative images showing mTFP (cyan) and Venus  (yellow) fluorescence in HBVPs  which have direct contact with control (upper panel) or MCT5  (lower panel) siRNA-treated BMECs. VECAD immunostaining  was used for endothelial staining. L. Quantification of the  mTFP/Venus  fluorescence ratio of laconic  in HBVPs  which have direct contact with control (siCON) or MCT5  (siMCT5) siRNA-treated BMECs. (n=8 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.)",
    "ncbi_link": "MCT5: 9122"
  },
  {
    "caption": "D.  Western blot analysis showing expression   level of MCT12  and β-actin in HBVPs and BMECs. E. Western blot analysis for siRNA efficiency of MCT12.",
    "ncbi_link": "MCT12: 387700"
  },
  {
    "caption": "G. Representative images showing mTFP (cyan) and Venus  (yellow) fluorescence in control (upper panel) or MCT12  (lower panel) siRNA treated HBVPs  in a 2 well chamber assay system with BMECs. VECAD  (purple) immunostaining  was used for endothelial staining. H. Quantification of the mTFP/Venus  fluorescence ratio of Laconic  in control (blue) or MCT12 (orange) siRNA treated HBVPs. (n=8 from independent experiments. Error bars indicate the standard error of the mean (SEM) from unpaired Student's t test.",
    "ncbi_link": "MCT12: 387700"
  },
  {
    "caption": "A. Permeability  assay  using vibratome  section showing the cadaverine 555 dye (red), CD31  (green) and CD13  (purple) in the  brain vasculature of  Glut1iECKO mice  with (bottom) or without (top) lactate  administration. Note the extravascular accumulation of cadaverine dye in control Glut1iECKO mice, but not in lactate  supplemented Glut1iECKO mice.",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "B. Quantification of the CD13-positive pericytes  coverage in the brain vasculature  of  Glut1iECKO mice  with (orange) or without (blue) lactate  administration. (n=16 from 5 independent experiments. Error bars indicate the standard error of the mean (SEM) from 1-way ANOVA.) C. Quantification of the number of cadaverine 555 positive  brain parenchyma  cells  in the brain vasculature  of  Glut1iECKO mice  with (orange) or without (blue) lactate  administration. (n=24 from 5 independent experiments. Error bars indicate the standard error of the mean (SEM) from 1-way ANOVA.) D. Quantification of CSF lactate  level in WT and Glut1iECKO mice  with/without lactate  supplementation. (n=3 from independent experiments. Error bars indicate the standard error of the mean (SEM) from 1-way ANOVA.)",
    "ncbi_link": "Glut1: 20525"
  },
  {
    "caption": "A. Western blot detection of PEX13, ATG7, SMURF1, and FANCC in HeLa/GFP-LC3cells transfected with the indicated siRNA. Asterisk denotes non-specific band.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "B. Representative images of GFP-LC3 colocalization with mCherry-capsid at 10 h after Sindbis virus (strain AO30) infection of HeLa/GFP-LC3 cells treated with the indicated siRNA. siPEX13 oligo #2 is shown; similar results were observed with three other siPEX13oligos. Arrowheads denote representative colocalized GFP-LC3/mCherry-capsid puncta. Scale bars, 10 μm.",
    "ncbi_link": "PEX13: 5194"
  },
  {
    "caption": "D. Western blot detection of Pex13 in MEFs of indicated genotype. Asterisks denote non-specific bands.",
    "ncbi_link": "Pex13: 72129"
  },
  {
    "caption": "A. Representative images of Parkin-mediated clearance of mitochondrial outer membrane protein TOMM20 in HeLa/Parkin cells treated with indicated siRNA 16 h after treatment with 10 μM CCCP or DMSO vehicle control. siPEX13 oligo #2 is shown; similar results were observed with three other siPEX13 oligos. Scale bars, 20 μm.B. Quantification of TOMM20 clearance in the experiment shown in (A). Results represent mean ± SEM of triplicate samples (~100 cells analyzed per sample). Similar results were observed in more than three independent experiments. *p<0.05, **p<0.01, ***p<0.001; one-way ANOVA with adjustment for multiple comparisons.",
    "ncbi_link": "PEX13: 5194"
  },
  {
    "caption": "C. Representative images of Parkin-mediated clearance of mitochondrial double-stranded DNA (mtDNA) in HeLa/HA-Parkin cells treated with indicated siRNA 8 h after treatment with 2.5 μM oligomycin and 250 nM antimycin A (OA) or DMSO vehicle control. siPEX13 oligo #1 is shown; similar results were observed with three other siPEX13 oligos. Nuclear DNA staining was masked using DAPI. Scale bars, 20 μm.D. Quantification of mtDNA clearance in the experiment shown in (C). Results represent box plots of ~300 cells analyzed per sample. Whiskers represent 5%-95% range, and each outlier is represented by a dot. Similar results were observed in three independent experiments. ****p<0.0001; Kruskal-Wallis H-test.",
    "ncbi_link": "Parkin: 5071
PEX13: 5194"
  },
  {
    "caption": "A. Western blot detection of PEX13 in HeLa/Parkin cells transfected with indicated siRNA and siRNA-resistant PEX13 plasmid. To achieve similar PEX13 protein expression levels, 0.75 μg PEX13 I326T and PEX13 W313G plasmids were transfected compared to 0.25 μg WT PEX13. Total plasmid level was adjusted using empty vector. Asterisk denotes non-specific band.",
    "ncbi_link": "Parkin: 5071
PEX13: 5194"
  },
  {
    "caption": "B. Representative images of Parkin-mediated clearance of TOMM20 in HeLa/Parkin cells treated with PEX13 siRNA and transfected with indicated PEX13 siRNA-resistant plasmid and then treated with CCCP (10 μM, 16 h). Scale bars, 20 μm. See Fig EV3B for representative images of mitochondrial morphology (TOMM20 staining) in control cells treated with DMSO.",
    "ncbi_link": "Parkin: 5071
PEX13: 5194"
  },
  {
    "caption": "D. Western blot detection of PEX13 expression in wild-type (WT) and PEX13 W313G (W313G) mutant primary human fibroblasts.",
    "ncbi_link": "PEX13: 5194"
  },
  {
    "caption": "E. Representative images of Parkin-mediated clearance of TOMM20 in wild-type (WT) and PEX13 W313G (W313G) mutant primary human fibroblasts treated with Oligomycin (2.5 μM) + Antimycin A (250 nM) for 24 h. Scale bars, 20 μm. W313G cells varied in morphology; outlined cell in upper right panel shows a representative cell with larger size and abnormal mitochondrial morphology (see Fig EV3C for higher resolution imaging) and outlined cell in lower right panel shows a representative cell with accumulation of fragmented mitochondria that would be scored as positive in (F).F. Quantification of experiment shown in (E). Results represent mean ± SEM of 5 groups of 10 images of random fields of cells (>350 cells analyzed per sample). Similar results were observed in two independent experiments. ***p<0.0001; two-tailed unpaired t-test.",
    "ncbi_link": "PEX13: 5194"
  },
  {
    "caption": "A-C Representative images of PEX13 and PMP70 (A), PEX13 and TOMM20 (B), or PEX13-Flag and WIPI2 (C) colocalization in HeLa/Parkin cells transfected with PEX13 after 4 h DMSO or CCCP treatment. Scale bars, 20 μm (A-B) and 5 μm (C).",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "D Western blot detection of endogenous PEX13 in HeLa/Parkin cells treated with 10 μM CCCP for the indicated time.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "A. Quantitative real-time PCR detection of mRNA levels for PEX3, PEX13, PEX14, and PEX19 in HeLa cells transfected with the indicated siRNA. ***p<0.001; two-tailed unpaired t-test.",
    "ncbi_link": "PEX13: 5194
PEX14: 5195
PEX19: 5824
PEX3: 8504"
  },
  {
    "caption": "B. Quantification of Parkin-mediated TOMM20 clearance in HeLa/Parkin cells transfected with the indicated siRNA 16 h after treatment with 10 µM CCCP. Results represent mean ± SEM of triplicate samples (~100 cells analyzed per sample). Similar results were observed in three independent experiments. **p<0.01, ***p<0.001; one-way ANOVA with adjustment for multiple comparisons.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "C. Quantification of mtDNA clearance in HeLa/HA-Parkin cells transfected with the indicated siRNA 8 h after treatment with 2.5 μM oligomycin and 250 nM antimycin A (OA). Results represent box plots of ~300 cells analyzed per sample. Whiskers represent 5%-95% range, and each outlier is represented by a dot. Similar results were observed in three independent experiments. ****p<0.0001, NS= not significant; Kruskal-Wallis H-test.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c) RNA expression changes for TFs related to 8-mer groups bZIP, CTCF, HIC1, and EGR. Significant changes relative to control samples are shown with asterisks (Wilcoxon rank sums test, two-sided).",
    "ncbi_link": "CTCF: 13018
EGR: 13653///13655///13654///13656
HIC1: 15248"
  },
  {
    "caption": "(c) Chromosome 15 genome tracks neighboring Arc, displaying ATAC-seq read counts per million (CPM); RNA-seq CPM; H3K27ac normalized signal upon KCl stimulation, H3K4me1(Malik et al, 2014); CTCF(Sams et al, 2016); and Cortical neurons Hi-C data(Bonev et al, 2017). Red bars in ATAC-seq tracks indicate gained DA-peaks in BDNF, and red bars in RNA-seq tracks indicate Arc differential expression in BDNF and KCl 1h. Green blocks in Hi-C tracks indicate anchor points for the calculation of contact scores, using shaman(Cohen et al, 2017). Line and Spearman's rho value indicate counts rank-based correlation between highlighted peaks across all samples (Appendix Figure S4c). TF module names indicate the presence of 8-mers in those peaks.",
    "ncbi_link": "Arc: 11838"
  },
  {
    "caption": "G) Western blot  analysis of siRNA knockdown of p53  expression in three biological replicates (n=3). Β-actin serves as an internal loading control.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(c) ATG14L-containing VPS34 complexes were immunopurified from WT, ULK1−/− 2KD (ULK def.) and FIP200−/− MEFs, and measured for lipid kinase activity as in a.",
    "ncbi_link": "FIP200: 12421
ULK1: 22241"
  },
  {
    "caption": "(d) VPS34 was immunopurified from WT, ULK-deficient and FIP200−/− MEFs. A kinase assay was performed as in a.",
    "ncbi_link": "FIP200: 12421
ULK: 71742///29869///22241"
  },
  {
    "caption": "(e) Immunoprecipitation of Beclin-1-containing VPS34 complexes from WT, ULK-deficient and FIP200−/− MEFs. A kinase assay was performed as in a.",
    "ncbi_link": "FIP200: 12421
ULK: 71742///29869///22241"
  },
  {
    "caption": "(j) VPS34 activity with or without ULK1 overexpression was assayed. A representative experiment of four repeats is shown.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "(a) HEK293 cells were transfected with ATG14L, VPS34 and Beclin-1. ATG14L-containing VPS34 complexes were immunopurified and subjected to an in vitro ULK1 kinase assay in the presence of γ-32P[ATP]. Bound ATG14L complexes and soluble ULK1 were separated and phosphorylation was detected by autoradiography (AR, left panels). Western blotting was performed (right panels). Results are representative of two unique experiments.",
    "ncbi_link": "ATG14L: 22863
ULK1: 8408"
  },
  {
    "caption": "(b) Full-length murine GST-Beclin-1 and various truncations (as labelled) were subjected to an in vitro HA-ULK1 kinase assay. GST-Beclin-1 6(S/T)A has serine/threonine residues 4, 7, 10, 14, 29 and 42 mutated to alanine. ULK1 inputs were determined by western blotting, Beclin-1 inputs by Coomassie (Coom) and target phosphorylation by autoradiography.",
    "ncbi_link": "Beclin-1: 56208"
  },
  {
    "caption": "(c) GST-Beclin-1 (1-85) was subjected to an in vitro ULK1 kinase reaction and analysed by mass spectrometry. Ser 14, Ser 15 in humans (outlined), is the main phosphorylation site identified (for mass spectrometry data, see Supplementary Fig. S2b,c). Mass spectrometry was performed on a single experiment.",
    "ncbi_link": "Beclin-1: 56208"
  },
  {
    "caption": "(d) Beclin-1 Ser 14 is the main in vitro ULK1 phosphorylation site. Beclin-1 WT, and S4A and S14A mutants were subjected to an in vitro ULK1 kinase assay. The reaction was developed by autoradiography and stained for Beclin-1 input levels by Coomassie blue. Results are representative of two unique experiments.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "(e) HEK293 cells were transfected with the indicated plasmids under nutrient-rich conditions. Beclin-1 was immunoprecipitated and immunoblotted with pBeclin-1(Ser 14), or anti-Beclin-1 as a loading control. ULK1 inputs are included below immunoprecipitated samples.",
    "ncbi_link": "Beclin-1: 8678
ULK1: 8408"
  },
  {
    "caption": "(f) Purified GST-Beclin-1 (1-85) was subjected to in vitro phosphorylation by GST-ULK1 (top panel) and GST-ULK2 (bottom panel). Reactions were immunoblotted with the indicated antibodies.",
    "ncbi_link": "ULK1: 8408
ULK2: 9706"
  },
  {
    "caption": "(g) HEK293 cells were transfected with ATG14L, VPS34 and Beclin-1 and grown under nutrient-rich conditions. ATG14L-containing VPS34 complexes were immunoprecipitated and lipid kinase activity was assayed as described in Fig. 1j. Inputs were immunoblotted with the indicated antibodies. Representative of four unique experiments.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678
VPS34: 5289"
  },
  {
    "caption": "(h) Stable lines containing Beclin-1(WT or S14A) were used for Beclin-1 immunoprecipitation. Binding partners were determined by SDS-PAGE analysis and western blot using the indicated antibodies. Uncropped images of blots are shown in Supplementary Fig. S4.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "(c) WT or FIP200−/− MEFs were incubated under nutrient-rich, amino-acid-deprived or Torin-1 (+T, an mTOR inhibitor) conditions. Beclin-1 was purified and immunoblotted as in Fig. 3b.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(d) WT or ULK-deficient MEFs were incubated with or without amino acids. Beclin-1 was purified and immunoblotted as in a. Two unique experiments were performed. Uncropped images of blots are shown in Supplementary Fig. S4.",
    "ncbi_link": "ULK: 71742///29869///22241"
  },
  {
    "caption": "(a) Beclin-1 alone (lanes 1-4) or Beclin-1 and ATG14L (lanes 5-8) were overexpressed in HEK293 cells. Beclin-1 was purified either by direct immunoprecipitation (lanes 1-4) or by ATG14L immunoprecipitation (lanes 5-8). Immunoprecipitated samples were subjected to an in vitro ULK1 kinase assay with increasing amounts of ULK1. Reactions were immunoblotted with the indicated antibodies. Black line denotes discontinuous lanes from the same gel. Two unique experiments were performed.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678
ULK1: 8408"
  },
  {
    "caption": "(c) An ATG14L-FLAG-6His-inducible U2OS cell line was induced for 16 h in the presence of amino acids. Endogenous Beclin-1 was immunoprecipitated and immunoblotted as in Fig. 3a. ATG14L input levels were detected by immunoblotting. Two unique experiments were performed.",
    "ncbi_link": "ATG14L: 22863"
  },
  {
    "caption": "(d) HEK293 cells transfected with either ATG14L or Beclin-1, or both, in conjunction with ULK1, were immunoprecipitated as indicated and blotted with the indicated antibodies.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678
ULK1: 8408"
  },
  {
    "caption": "(e) HEK293 cells were transfected with Beclin-1 and ULK1 in the presence of ATG14L WT or ATG14LΔCCD, which is defective in Beclin-1 binding, under nutrient-rich conditions. Lysates were resolved by SDS-PAGE and blotted with the indicated antibodies.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678
ULK1: 8408"
  },
  {
    "caption": "(f) HEK293 cells were transfected with ULK1 and Beclin-1 in conjunction with either ATG14L WT, or one of two mutants (ΔBATS,ΔN) that are defective in phagophore localization. Samples were handled as in e. Uncropped images of blots are shown in Supplementary Fig. S4. Lysates were resolved by SDS-PAGE and blotted with the indicated antibodies.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678
ULK1: 8408"
  },
  {
    "caption": "(a) HEK293 cells were transfected with Beclin-1, with or without UVRAG, in conjunction with ULK1 as indicated in the presence of amino acids. Lysates were immunoblotted with the indicated antibodies. A representative experiment of three repeats is shown.",
    "ncbi_link": "Beclin-1: 8678
ULK1: 8408
UVRAG: 7405"
  },
  {
    "caption": "(b) UVRAG bridges the interaction between Beclin-1 and ULK1. HEK293 cells were transfected with Beclin-1, with or without UVRAG, in conjunction with ULK1 as indicated. Lysates were immunoprecipitated with anti-HA(Beclin-1) antibody and blotted with the indicated antibodies. A representative experiment of three repeats is shown. Uncropped images of blots are shown in Supplementary Fig. S4.",
    "ncbi_link": "Beclin-1: 8678
ULK1: 8408
UVRAG: 7405"
  },
  {
    "caption": "(b) HEK293 cells transfected with Beclin-1 ATG14L were grown in the presence or absence of amino acids. Lysates were immunoblotted with the indicated antibodies (left panel) and quantified by densitometry (right panel). Data represent mean+s.d. of three unique experiments.",
    "ncbi_link": "ATG14L: 22863
Beclin-1: 8678"
  },
  {
    "caption": "(c) Beclin-1-shRNA reconstituted lines (WT or mutant) and controls (scramble shRNA or Beclin-1 shRNA) were grown with or without amino acids and assessed for autophagy (left panel) and Beclin-1 levels (right panel).",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "(f) HA-Beclin-1 WT or S14D was transiently expressed in FIP200−/− MEFs grown under nutrient-rich conditions. Indirect immunofluorescence was performed using antibodies against endogenous LC3B and HA-Beclin-1. Scale bars, 20 μm. (g) Quantification of LC3B puncta from confocal in f. In the HA-Beclin-1- or HA-Beclin-1-S14D-transfected samples, only the HA-positive cells were counted for LC3B puncta. Error bars were processed as in e. Mean value shown; P values determined by Student's t-test using 10 unique fields of view from f. Uncropped images of blots are shown in Supplementary Fig. S4.",
    "ncbi_link": "Beclin-1: 56208
FIP200: 12421"
  },
  {
    "caption": "(a) Bec-1C. elegans were reconstituted with either WT or mutant GFP-BEC-1. Stable worm lines with Bec-1 rescue were obtained and embryos were stained with anti- PGL-1 antibody. Arrowheads indicate normal PGL-1 staining in germline cells. (b) Quantification of PGL-1 puncta outside germline cells (left panel). Error bars represents s.d. between 3 unique embryos in a representative experiment. Reconstituted Bec-1 (WT and mutant) levels in Bec−/− stable worms were compared by western blotting. Mean value presented.",
    "ncbi_link": "Bec-1: 177345"
  },
  {
    "caption": "(c) Spectrum of defects in PGL granule degradation in bec-1 mutant rescue embryos. Mutant embryos exhibited either high levels of diffuse PGL-1 staining (middle-left panel; one-third of the embryos), or large punctuate PGL-1 structures in somatic cells (bottom-left panel; two-thirds of the embryos). Both diffuse or punctuate PGL-1 staining in somatic cells have been described in autophagy-deficient embryos.",
    "ncbi_link": "bec-1: 177345"
  },
  {
    "caption": "(d) Embryos from the lines described in a were labelled with anti-LGG-1, along with WT and unc-51 worms. Representative embryos at ∼ 100 cell stage are shown. (e) Quantification of LGG-1 per embryo from labelling in d. Error bars generated as in b. Mean value presented. Uncropped images of blots are shown in Supplementary Fig. S4. Scale bar, 10 μm.",
    "ncbi_link": "unc-51: 180311"
  },
  {
    "caption": "(A) 293T cells were co-transfected with expression plasmids for Cherry-STING, the murine IFNβ-luciferase reporter (IFNβ-Luc), a Renilla luciferase normalization control (pRL-TK) and the indicated expression plasmids or empty vector (ev). Cells were additionally co-transfected with expression plasmids for cGAS-GFP (stimulated) or IRES-GFP (unstimulated). 20 hours post transfection, cells were lysed and a dual-luciferase assay was performed. Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "Cherry: 
GFP: 
Luc: 
luciferase: 
pRL: 
TK: 
cGAS: 115004
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(B) An expression plasmid for RIG-I N (stimulated) or ev (unstimulated) was co-transfected with IFNβ-Luc, pRL-TK and the indicated expression plasmids in 293T cells and analyzed as in (A). Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "Luc: 
pRL: 
RIG-I: 
TK: 
IFNβ: 15977"
  },
  {
    "caption": "(C) An expression plasmid for TBK1 (stimulated) or ev (unstimulated) was co-transfected together with IFNβ-Luc, pRL-TK and the indicated expression plasmids and analyzed as in (A). Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "Luc: 
pRL: 
TK: 
IFNβ: 15977
TBK1: 56480"
  },
  {
    "caption": "(D) 293T cells were co-transfected with a plasmid expressing constitutively active IRF3 (IRF3-5D; stimulated) or IRES-GFP (unstimulated) together with IFNβ-Luc, pRL-TK and the indicated expression plasmids and analyzed as in (A). Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "GFP: 
Luc: 
pRL: 
TK: 
IFNβ: 15977
IRF3: 3661"
  },
  {
    "caption": "(E) The ISG56-luciferase reporter, pRL-TK and the indicated expression plasmids were co-transfected in 293T cells. 24 hours post transfection, cells were stimulated with 0.1 ng/µl human IFNβ or mock stimulated and analyzed 16 hours later as described in (A). Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "ISG56: 
luciferase: 
pRL: 
TK: "
  },
  {
    "caption": "(F-G) iMEFgt/gt stably expressing Cherry-STING and either ev or V5-tagged m152 were stimulated with 5 µg/ml ISD (F), 10 µg/ml poly(I:C) (G) or mock stimulated with Lipofectamine. 4 hours post stimulation, RNA was extracted to determine IFNβ mRNA transcripts by qRT-PCR. Data information: (A-G) Data is combined from three independent experiments.",
    "ncbi_link": "Cherry: 
m152: 
V5: 
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(H-K) iBMDM stably expressing ev or m152-V5 were stimulated in duplicates with 10 µg/ml cGAMP (H), 6 (H) or 16 (I-K) hours later, secreted IFNβ (H-J) levels were determined by ELISA. (H-K) Experiments were performed three (H, I, K) or two (J) times independently and one representative experiment is shown. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Data are shown as mean ± SD. ",
    "ncbi_link": "m152: 
V5: "
  },
  {
    "caption": "(H-K) iBMDM stably expressing ev or m152-V5 were stimulated in duplicates with 5 µg/ml ISD (I), 6 (H) or 16 (I-K) hours later, secreted IFNβ (H-J) levels were determined by ELISA. (H-K) Experiments were performed three (H, I, K) or two (J) times independently and one representative experiment is shown. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Data are shown as mean ± SD. ",
    "ncbi_link": "m152: 
V5: "
  },
  {
    "caption": "(H-K) iBMDM stably expressing ev or m152-V5 were stimulated in duplicates with Newcastle's Disease Virus (NDV) infection (J) 6 (H) or 16 (I-K) hours later, secreted IFNβ (H-J) levels were determined by ELISA. (H-K) Experiments were performed three (H, I, K) or two (J) times independently and one representative experiment is shown. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Data are shown as mean ± SD. ",
    "ncbi_link": "m152: 
V5: "
  },
  {
    "caption": "(H-K) iBMDM stably expressing ev or m152-V5 were stimulated in duplicates with µM CpG DNA (K). 6 (H) or 16 (I-K) hours later, TNFα (K) levels were determined by ELISA. (H-K) Experiments were performed three (H, I, K) or two (J) times independently and one representative experiment is shown. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Data are shown as mean ± SD. ",
    "ncbi_link": "CpG DNA: 
m152: 
V5: "
  },
  {
    "caption": "(A) HeLa cells were co-transfected with expression plasmids for Cherry-STING, V5-tagged m152 and either ev (unstimulated) or cGAS-GFP (stimulated).",
    "ncbi_link": "Cherry: 
GFP: 
m152: 
V5: 
cGAS: 115004
STING: 72512"
  },
  {
    "caption": "(B) iMEFgt/gt were co-transfected with expression plasmids for V5-tagged m152 together with either Cherry-STING or ev in combination with cGAS-GFP (stimulated) or ev (unstimulated). 24 hours post transfection cells were fixed for immunolabeling with an anti-V5 antibody. White boxes indicate the region shown at a higher magnification. Scale bar represents 10 µm.",
    "ncbi_link": "Cherry: 
GFP: 
m152: 
V5: 
cGAS: 115004
STING: 72512"
  },
  {
    "caption": "(C) Lysates of Cherry-STING and either CD4-V5 or m152-V5 expressing 293T cells were subjected to immunoprecipitation (IP) with an anti-V5 antibody. Input and IP samples were analyzed by IB with the indicated antibodies. Data information: IB shown are representative of three (C) or two (D) independent experiments.",
    "ncbi_link": "Cherry: 
m152: 
V5: 
CD4: 12504
STING: 72512"
  },
  {
    "caption": "(D) iMEF stably expressing ev or m152-V5 were left unstimulated or stimulated with 10 µg/ml ISD and lysed 90 minutes later. m152 was immunoprecipitated with an anti-V5 antibody and samples were analyzed by IB with V5, STING and phospho-TBK1 (pTBK1) specific antibodies. Data information: IB shown are representative of three (C) or two (D) independent experiments.",
    "ncbi_link": "m152: 
V5: "
  },
  {
    "caption": "(B) Cherry-STING, IFNβ-Luc, pRL-TK, cGAS-GFP (stimulated) or IRES-GFP (unstimulated) and indicated expression plasmids as shown in (A) were transiently expressed in 293T cells and a dual luciferase assay was performed. Data is combined from two out of three independent experiments and shown as mean ± SD. Data information: Student's t-test (unpaired, two-tailed), n.s. not significant, **p<0.01, ***p<0.001, ****p<0.0001",
    "ncbi_link": "Cherry: 
GFP: 
Luc: 
pRL: 
TK: 
cGAS: 115004
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(C) 293T cells were co-transfected with expression plasmids for Cherry-STING and indicated chimeras as shown in (A). An anti-V5 IP was performed and samples were analyzed by IB with indicated antibodies. IB shown is representative of three independent experiments.",
    "ncbi_link": "Cherry: 
STING: 72512"
  },
  {
    "caption": "(D) Cherry-STING, IFNβ-Luc, pRL-TK and either CD4, m152, m152-Δstalk or m152-GSstalk were transiently expressed in 293T cells. For stimulation, samples were co-transfected with cGAS-GFP, and unstimulated samples with IRES-GFP. Lysates were analyzed as described in (B). Data is combined from two out of three independent experiments and shown as mean ± SD. Data information: Student's t-test (unpaired, two-tailed), n.s. not significant, **p<0.01, ***p<0.001, ****p<0.0001",
    "ncbi_link": "Cherry: 
GFP: 
Luc: 
m152: 
pRL: 
TK: 
CD4: 12504
cGAS: 115004
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(E) 293T cells were co-transfected with expression plasmids for Cherry-STING and either CD4, m152, m152-Δstalk or m152-GSstalk. An anti-V5 IP was performed and samples were analyzed by IB with indicated antibodies. Immunoblot shown is representative of three independent experiments.",
    "ncbi_link": "Cherry: 
m152: 
CD4: 12504
STING: 72512"
  },
  {
    "caption": "(A) 293T cells were co-transfected with expression plasmids for IFNβ-Luc, pRL-TK, cGAS-GFP (stimulated) or IRES-GFP (unstimulated) and indicated expression plasmids together with murine Cherry-STING (left panel) or human STING (right panel). Lysates were analyzed by dual-luciferase assay. Data is combined from two out of three independent experiments and shown as mean ± SD.",
    "ncbi_link": "Cherry: 
GFP: 
Luc: 
pRL: 
TK: 
cGAS: 115004
IFNβ: 15977
STING: 72512
STING: 340061"
  },
  {
    "caption": "(C) IFNβ-Luc, pRL-TK, cGAS-GFP (stimulated) or IRES-GFP (unstimulated) and either LacZ or m152 together with the indicated murine STING mutants described in (B) were transiently expressed in 293T cells. Luciferase activity was measured as described in (A). Data information: Data in (C) is normalized to LacZ, combined from three independent experiments and shown as mean ± SD.",
    "ncbi_link": "GFP: 
LacZ: 
Luc: 
m152: 
pRL: 
TK: 
cGAS: 115004
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(D) 293T cells were co-transfected with expression plasmids for either LacZ or m152 together with the indicated murine STING mutants described in (B). An anti-V5 IP was performed and samples were analyzed by IB with the indicated antibodies. IB shown in (D) representative of three independent experiments.",
    "ncbi_link": "LacZ: 
m152: 
V5: 
STING: 72512"
  },
  {
    "caption": "(E-F) Luciferase assay (E) were performed as described in (C) and (D), respectively, using the indicated human STING mutants in place of the murine STING mutants described in (B). Data information: Data in (E) is normalized to LacZ, combined from three independent experiments and shown as mean ± SD.",
    "ncbi_link": "LacZ: 
STING: 340061
STING: 72512"
  },
  {
    "caption": "(E-F) co-IP (F) were performed as described in (C) and (D), respectively, using the indicated human STING mutants in place of the murine STING mutants described in (B). Data information: IB shown in (F) are representative of three independent experiments.",
    "ncbi_link": "STING: 340061
STING: 72512"
  },
  {
    "caption": "(B) 293T cells were co-transfected with expression plasmids for IFNβ-Luc, pRL-TK and either ev or m152. Cells were further co-transfected with either Cherry-STING WT or the constitutively active Cherry-STING V154M (stimulated) or with IRES-GFP (unstimulated). Data is combined from three independent experiments and shown as mean ± SD.",
    "ncbi_link": "Cherry: 
GFP: 
Luc: 
m152: 
pRL: 
TK: 
IFNβ: 15977
STING: 72512"
  },
  {
    "caption": "(C) iMEF stably expressing ev or m152-V5 were stimulated with 10 µg/ml ISD for the indicated times or left unstimulated (mock). Cell lysates were analyzed by SDS-PAGE under non-reducing conditions and subjected to IB with the specified antibodies. Data information: IB shown in (C) are representative of three and two independent experiments, respectively. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, ****p<0.0001",
    "ncbi_link": "m152: 
V5: "
  },
  {
    "caption": "(D) Two representative still images from live cell imaging experiments with iMEFgt/gt stably expressing Cherry-STING transfected with ISD (right panel) or left unstimulated (left panel). Red circles highlight representative translocated STING in ISD stimulated cells, which is used as an indicator of activation.",
    "ncbi_link": "Cherry: 
STING: 72512"
  },
  {
    "caption": "(E) iMEFgt/gt stably expressing Cherry-STING and either ev or m152-V5 were stimulated with ISD. Live cell imaging was performed and STING translocation quantified 120 min and 180 min post stimulation. Data shown is one representative of two independent experiments.",
    "ncbi_link": "Cherry: 
m152: 
V5: 
STING: 72512"
  },
  {
    "caption": "(F) iMEFgt/gt stably expressing Cherry-STING and V5-tagged m152 or corresponding ev were stimulated with 5 µg/ml ISD for the indicated time or left unstimulated (mock). Lysates were subjected to IB with the specified antibodies. Data information: IB shown in (C) and (F) are representative of three and two independent experiments, respectively. Student's t-test (unpaired, two-tailed), n.s. not significant, *p<0.05, ****p<0.0001",
    "ncbi_link": "Cherry: 
m152: 
V5: 
STING: 72512"
  },
  {
    "caption": "(B) iMEF were infected by centrifugal enhancement with either parental MCMV (par.) or MCMV m152stop at an MOI of 0.5 or mock infected. 3 hours post infection (hpi) cells were lysed and subjected to immunoblotting (IB) with the specified antibodies.",
    "ncbi_link": "m152: "
  },
  {
    "caption": "(C) iMEF and iMEFgt/gt were infected by centrifugal enhancement with parental MCMV or MCMV m152stop, or parental MCMV alone, respectively (MOI 0.5). 3 hpi lysates were subjected to an anti-m152 IP and samples were analyzed by IB with indicated antibodies. IB shown is representative of two independent experiments.",
    "ncbi_link": "m152: "
  },
  {
    "caption": "(D) Primary BMDM were infected with parental MCMV (par.) or MCMV m152stop at an MOI of 0.1 or mock infected. 16 hpi secreted levels of IFNα or IFNβ were quantified by ELISA. Data is representative of two independent experiments.",
    "ncbi_link": "m152: "
  },
  {
    "caption": "(E) iMEFgt/gt stably expressing Cherry-STING were infected with parental MCMV or MCMV m152stop (MOI 0.5). Live cell imaging was performed and STING translocation quantified 120 min and 180 min post stimulation. Data shown is one representative of two independent experiments.",
    "ncbi_link": "Cherry: 
m152: 
STING: 72512"
  },
  {
    "caption": "(F-G) iMEF or iMEFgt/gt were infected by centrifugal enhancement with parental MCMV or MCMV m152stop (MOI 0.01). At 6 hpi total RNA was extracted to determine MCMV IE1 and MCMV E1 (F), transcripts by qRT-PCR. Data shown is combined from two out of three independent experiments.",
    "ncbi_link": "E1: 
IE1: 
m152: "
  },
  {
    "caption": "(F-G) iMEF or iMEFgt/gt were infected by centrifugal enhancement with parental MCMV or MCMV m152stop (MOI 0.01). At 6 hpi total RNA was extracted to determine , IFNb1 and IL6 (G) transcripts by qRT-PCR. Data shown is combined from two out of three independent experiments.",
    "ncbi_link": "m152: 
IFNb1: 15977
IL6: 16193"
  },
  {
    "caption": "(H) 293T cells were co-transfected with Cherry-STING, the pNF-κB luciferase reporter, pRL-TK, cGAS-GFP (stimulated) or IRES-GFP (unstimulated) and either ev or m152. Cells were lysed and analyzed as described in Figure 1. Data is combined from three independent experiments.",
    "ncbi_link": "Cherry: 
GFP: 
luciferase: 
m152: 
pRL: 
TK: 
cGAS: 115004
pNF-κB: 18033
STING: 72512"
  },
  {
    "caption": "(A-C) Type I IFN levels in spleen homogenates (A) and serum (B) of C57BL/6J (B6J) or STING-/- mice following i.v. infection with 4 x 105 PFU parental MCMV or MCMV m152stop were analyzed 6 hpi by ELISA. IFNβ levels of STING-/- mice were below the detection limit (n.d.).",
    "ncbi_link": "m152: 
STING: 72512"
  },
  {
    "caption": "IL6 levels in spleen homogenates (C) of C57BL/6J (B6J) or STING-/- mice following i.v. infection with 4 x 105 PFU parental MCMV or MCMV m152stop were analyzed 6 hpi by ELISA.",
    "ncbi_link": "m152: 
STING: 72512"
  },
  {
    "caption": "(D) B6J or STING-/- mice were i.v. infected with 4 x 105 PFU parental MCMV or MCMV m152stop. 6 hpi, RNA was extracted from spleen homogenates and expression of MCMV IE1 and E1 transcripts was determined by qRT-PCR. Data were normalized to 107 cellular β-actin transcripts (D-F).",
    "ncbi_link": "E1: 
IE1: 
m152: 
β-actin: 
STING: 72512"
  },
  {
    "caption": "(E) B6J or STING-/- mice were i.v. infected with 4 x 105 PFU parental MCMV. 6 hpi, RNA was extracted from spleen homogenates and m152 transcript levels were determined by qRT-PCR. Data were normalized to 107 cellular β-actin transcripts (D-F).",
    "ncbi_link": "m152: 
β-actin: 
STING: 72512"
  },
  {
    "caption": "(F) B6J or STING-/- mice were depleted of NK cells via treatment with anti-NK1.1 (right panel) or left untreated (left panel). One day after NK cell depletion, B6J or STING-/- mice were i.v. infected with 4 x 105 PFU parental MCMV or MCMV m152stop. 16 hpi, RNA was extracted from spleen homogenates and MCMV E1 transcript levels were determined by qRT-PCR. Data were normalized to 107 cellular β-actin transcripts (D-F).",
    "ncbi_link": "E1: 
m152: 
β-actin: 
STING: 72512"
  },
  {
    "caption": "(A) 293T cells were co-transfected with Cherry-STING, pRL-TK, cGAS-GFP (stimulated) or IRES-GFP (unstimulated) and either the pNF-κB, p55-CIB, p125 or p125AA luciferase reporter. Data is representative of two independent experiments.",
    "ncbi_link": "Cherry: 
GFP: 
luciferase: 
pRL: 
TK: 
cGAS: 115004
STING: 72512"
  },
  {
    "caption": "(B) 293T cells were co-transfected with expression plasmids for cGAS-GFP (stimulated) or ev (unstimulated) together with either cherry-tagged WT STING or cherry-tagged K288R STING. Cells were fixed for imaging 24 hours post transfection. Scale bar represents 10 µm.",
    "ncbi_link": "cherry: 
GFP: 
cGAS: 115004
STING: 72512"
  },
  {
    "caption": "(C-D) iMEFgt/gt stably expressing cherry-tagged WT STING or K288R STING and either ev or V5-tagged m152 were stimulated with ISD (10 µg/ml) or mock stimulated. At 4 hpi total RNA was extracted to determine IFNb1 (C) and IL6 (D) transcripts by qRT-PCR. Data shown is combined from three (C) or two (D) out of three independent experiments.",
    "ncbi_link": "cherry: 
m152: 
V5: 
IFNb1: 15977
IL6: 16193
STING: 72512"
  },
  {
    "caption": "(E) iMEFgt/gt (-) and iMEFgt/gt stably expressing either cherry-tagged WT STING or K288R STING were infected by centrifugal enhancement with parental MCMV or MCMV m152stop (MOI 0.01). 6 hpi total RNA was extracted to determine MCMV E1 transcripts by qRT-PCR. Data shown is combined from three independent experiments.",
    "ncbi_link": "E1: 
cherry: 
m152: 
STING: 72512"
  },
  {
    "caption": "b, Starved NRK cells expressing LAMP1-YFP show tubules (arrows). Box is expanded on the right.",
    "ncbi_link": "LAMP1: 25328"
  },
  {
    "caption": "d, LAMP1-YFP expressing NRK-LC3 cells as in a. Arrows show reformation tubules. e, Three-dimensional reconstruction of a cell from d.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "a, TEM (bottom; scale bar, 5 µm) and fluorescence (top; scale bar, 10 µm) of NRK-LC3 cells starved for times shown with enlargements (boxes).",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "b, d, Immunoblots of cells shown in a with indicated antibodies (d, after transfection with non-specific (NS) or atg5 RNAi). c, Autophagy (black lines  show  independent experiments) and phospho-S6K percentage (densitometry of data shown in b, red line).",
    "ncbi_link": "atg5: 365601"
  },
  {
    "caption": "e-g, LAMP1-YFP NRK-LC3 cells starved for 2 h and then treated with 100 nM rapamycin for another 4 h (total, 6 h) or 6 h (total, 8 h) analysed by blotting (e) as in b or microscopy (f; scale bar, 5 µm) with quantification (g). Error bars, s.e.m.; n = 3.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "a, LAMP1/LC3NRK cells were starved for 4 h and treated with GTPγS for 6 h of further starvation.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "b, Rab7Q67L-GFP-transfected LC3-CFP/Lamp1-RFP NRK cells starved for 10 h.",
    "ncbi_link": "Lamp1: 25328
LC3: 362245///64862
Rab7: 501854///29448"
  },
  {
    "caption": "c, Rab7-CFP NRK cells starved for 2 h and treated with 100 nM rapamycin for 8 h of further starvation.",
    "ncbi_link": "Rab7: 501854///29448"
  },
  {
    "caption": "d, LAMP1-YFP NRK-LC3 cells starved for times shown with 1 µg ml-1 leupeptin and blotted with indicated antibodies. e, Cells in d imaged..",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "(B) HCT116 cells in which eIF3k was homozygously modified with the mAID domain to trigger auxin-dependent degradation were exposed to 500 μM indole-3-acetic acid (IAA) for the periods shown, and cell lysate was subjected to immunoblotting with the indicated antibodies",
    "ncbi_link": "eIF3k: 27335"
  },
  {
    "caption": "(A) eIF3k-mAID cells were maintained in media containing different concentrations of FBS and DMSO or IAA as indicated, and cell numbers were determined at various time points. Data represent means ± SD, n = 3 biological replicates. Numbers indicate p values",
    "ncbi_link": "eIF3k: 27335"
  },
  {
    "caption": "(B) eIF3k-mAID cells were serum starved by maintaining in media containing 0% FBS for 24 h. During the last 12 h of starvation, DMSO or IAA was added as indicated. Cells were re-stimulated with media containing 10% FBS, and the expression of the indicated proteins was followed of a period of 120 minutes. The data from triplicate experiments were quantified and plotted as relative ratios of phosphorylated to unphosphorylated species. Bars represent means ± SD, n = 3 Numbers indicate p values (unpaired Student's t-test).",
    "ncbi_link": "eIF3k: 27335"
  },
  {
    "caption": "(C) eIF3k-mAID cells were exposed to IAA or DMSO for 12 hours, followed by the addition of increasing concentrations of rapamycin for 1 h. The expression of the indicated proteins was determined by immunoblotting. The data from triplicate experiments were quantified and plotted as relative ratios of phosphorylated to unphosphorylated species. Bars represent means ± SD, n = 3 Numbers indicate p values (unpaired Student's t-test).",
    "ncbi_link": "eIF3k: 27335"
  },
  {
    "caption": "(C) Total ribosome occupancy of the indicated mRNAs in eIF3k-mAID cells exposed to DMSO or IAA for 12 hours was determined by RT-qPCR of RNA across a sucrose density gradient Bars represent means ± SD, n = 3; numbers indicate p values (unpaired Student's t-test). Triplicate RT-qPCR data across the sucrose gradient are shown below the bar graphs.",
    "ncbi_link": "eIF3k: 27335"
  },
  {
    "caption": "(D) Equal numbers of eIF3k-mAID cells stably expressing ectopic RPS15A (pCDH-RPS15A) or empty vector (pCDH) were plated and counted over a period of 6 days. Graphs represent means ± SD, n = 3. Numbers indicate p values",
    "ncbi_link": "eIF3k: 27335
RPS15A: 6210"
  },
  {
    "caption": "(G) Equal numbers of eIF3k-mAID cells stably expressing ectopic RPS4X (pCDH-RPS4X) or empty vector (pCDH) were plated and counted over a period of 6 days. Graphs represent means ± SD, n = 3. Numbers indicate p values Total ribosome content of these cells was determined as described in (A).",
    "ncbi_link": "eIF3k: 27335
RPS4X: 6191"
  },
  {
    "caption": "(B) Parental eIF3k-mAID cells or S15A-eIF3KO cells (clones #45 and # 361) were maintained in standard media, and cell numbers were determined at various time points. Data represent means ± SD, n = 3. Asterisks denote: * p < 0.005, ** p < 0.00005, *** p < 0.000005",
    "ncbi_link": "eIF3k: 27335
S15A: 6210"
  },
  {
    "caption": "(D) Relative translational efficiencies (TEs) of mRNAs encoding RPS15A, RPS4X, and RPL7A before and after depletion of eIF3k were determined in the indicated cell lines. RT-qPCR was performed on total RNA and on RNA contained within polysomal fractions > 2 ribosomes, and TE was calculated according to the formula TE = polysomal mRNA / total mRNA. Bars represent means ± SD, n = 3; numbers indicate p values (unpaired Student's t-test).",
    "ncbi_link": "eIF3k: 27335
RPL7A: 6130
RPS15A: 6210
RPS4X: 6191"
  },
  {
    "caption": "(A) Parental eIF3k-mAID cells or S15A-eIF3KO cells (clones #45 and # 361) were maintained in media with DMSO or IAA, and cell numbers were determined at various time points. Data represent means ± SD (too small to be visible), n = 3. All p values were > 0.45 except at the single time point where indicated otherwise.",
    "ncbi_link": "eIF3k: 27335
S15A: 6210"
  },
  {
    "caption": "(D) Total ribosome occupancy of the indicated mRNAs in S15A-eIF3KO (clone #361) cells exposed to DMSO or IAA for 12 hours was determined by RT-qPCR of RNA across a sucrose density gradient Bars represent means ± SD, n = 3; numbers indicate p values (unpaired Student's t-test). Triplicate RT-qPCR data across the sucrose gradient are shown below the bar graphs.",
    "ncbi_link": "S15A: 6210"
  },
  {
    "caption": "(E) RNA immunoprecipitation. eIF3k-mAID and S15A-eIF3KO (clone #361) cells were exposed to DMSO or IAA for 12 hours. Cell lysates were employed in immunoprecipitation with eIF3c antibodies and co-precipitated mRNAs were quantified by qPCR. Bars represent means ± SD, n = 4; numbers indicate p values (unpaired Student's t-test).",
    "ncbi_link": "eIF3k: 27335
S15A: 6210"
  },
  {
    "caption": "(A) Comparative permissiveness of various organs from B6.K18-hACE2IP-THV and B6.K18-ACE22prlmn/Jax transgenic mice (n = 5-6/group) to SARS-CoV-2 replication, as determined at 3 dpi by conventional E-specific or sub-genomic Esg-specific  qRT-PCR. Red lines indicate the  qRT-PCR  limits of detection. (B) Comparative quantitation of  hACE-2 mRNA in the  lungs  and  brain of B6.K18-hACE2IP-THV and B6.K18-ACE22prlmn/Jax transgenic mice (n = 5-6/group). Data information: Statistical significance was evaluated by Mann-Whitney test (*= p < 0.05, **= p <0.01, ns = not significant).",
    "ncbi_link": "hACE-2: 59272
ACE2: 59272
hACE2: 59272
Esg: 43740570
K18: 100775105"
  },
  {
    "caption": "(C) Heatmaps represent log2 fold change in cytokine and chemokine mRNA expression in the lungs or brain  of B6.K18-hACE2IP-THV and B6.K18-ACE22prlmn/Jax mice at 3 dpi (n = 5-6/group). Data were normalized versus untreated controls.",
    "ncbi_link": "ACE2: 59272
hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "(C)  Viral RNA  content as determined in various organs at 3 dpi (n = 6/group) by use of conventional E-specific or sub-genomic  Esg-specific  qRT-PCR. Red lines indicate the qRT-PCR detection limits. Data information: Statistical significance was evaluated by Mann-Whitney test (* = p<0.05, ** = p<0.01).",
    "ncbi_link": "Esg: 43740570"
  },
  {
    "caption": "(D) Percentages of NK cells or neutrophils in the lungs  of LV::S- or sham-vaccinated and SARS-CoV-2-challenged B6.K18-hACE2IP-THV transgenic mice  at 3 dpi (n = 6/group). Percentages were calculated versus total lung live  CD45+ cells. Data information: Statistical significance was evaluated by Mann-Whitney test (* = p<0.05, ** = p<0.01).",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "(E) Relative log2 fold change in cytokine and chemokine mRNA expression in the  brain of LV::S- or sham-immunized and SARS-CoV-2-challenged B6.K18-hACE2IP-THV transgenic mice at 3 dpi (n = 6/group). Means ± SD are shown. Data were normalized versus untreated controls. Data information: Statistical significance was evaluated by Mann-Whitney test (* = p<0.05, ** = p<0.01). ",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "B6.K18-hACE2IP-THV mice were primed (i.m.) at wk 0 and boosted (i.n.) at wk 5 (n = 5) with non-integrative LV::S. Control mice were injected with an empty LV (sham). (B, C) Cytometric strategy to detect  lung CD8+ T central memory (Tcm, CD44+CD62L+CD69-), T effector memory  (Tem, CD44+CD62L-CD69-) and T resident memory (Trm, CD44+CD62L-CD69+CD103+) and (C) percentages of these subsets among CD8+ T-cells in LV::S-vaccinated (n = 9) or sham (n = 5)  mice. Data information: Statistical significance of the difference between the two groups was evaluated by Mann-Whitney test (*= p < 0.05, **= p <0.01).",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "B6.K18-hACE2IP-THV mice  were primed (i.m.) at wk 0 and boosted (i.n.) at wk 5 (n = 5) with non-integrative LV::S. Control  mice were injected with an empty LV (sham). (D)  Cytometric strategy to detect  SCoV-2-specific CD8+ T  cells by use of the H-2Db-SCoV-2:538-546 dextramer in the lungs of LV::S or sham-vaccinated mice. Inside  CD8+ dextramer+ T-cell subset, Tcm, Tem and Trm have been distinguished.",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "B6.K18-hACE2IP-THV mice were primed (i.m.) at wk 0 and boosted (i.n.) at wk 5 (n = 5) with non-integrative LV::S. Control mice were injected with an empty LV (sham). (F, G) Anti-SCoV-2 IgG or  IgA  titers (F) and neutralizing activity (EC50) (G) in the  sera or lung homogenates at 3 dpi. Samples from individual mice (n = 4/group) were studied. Data information: Statistical significance of the difference between the two groups was evaluated by Mann-Whitney test (*= p < 0.05, **= p <0.01). ",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "(A) B6.K18-hACE2IP-THV mice were immunized with LV::S via i.m. or i.n. at wk 0 and boosted via i.m. or i.n. at wk 5 (n = 5/group) with non-integrative LV::S. Control mice were injected i.m. i.n. with an empty LV (sham). Viral RNA  contents were determined by conventional E-specific RT-PCR at 3 dpi, in the brain, lung and nasal washes. Data information: Statistical significance was evaluated by Mann-Whitney test (*= p < 0.05, **= p <0.01, ****= p < 0.0001, ns = not significant).",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "(B) Lung histology in B6.K18-hACE2IP-THV mice, vaccinated with LV::S after SARS-CoV-2 inoculation. H&E (rows 1 and 3) (scale bar: 500 μm) and NCoV-2-specific  IHC (rows 2 and 4) (scale bar: 50 μm)  staining of whole lung sections (scale bar: 50 μm) from the primed (i.m.), boosted (i.n.) and challenged B6.K18-hACE2IP-THV mice compared with their sham controls. H&E and NCoV-2-specific  IHC were performed on contiguous sections. The IHC fields correspond to the rectangles in the corresponding H&E images above them. A representative NCoV-2-specific IHC on a lung section from a non-infected (NI) mouse is also shown.",
    "ncbi_link": "hACE2: 59272
K18: 100775105"
  },
  {
    "caption": "(B) Brain or lung viral RNA contents, determined by conventional E-specific or sub-genomic Esg-specific qRT-PCR  at 3 dpi. Two mice out of the 5 sham-vaccinated mice  did not have detectable viral RNA  in the lungs  despite high  viral RNA content in the brain  and  hACE2  mRNA expression levels comparable to that of the other mice in the same group. Data information: Statistical significance was evaluated by Mann-Whitney test (*= p < 0.05, **= p < 0.01, ****= p < 0.0001).",
    "ncbi_link": "hACE2: 59272
Esg: 43740570"
  },
  {
    "caption": "(E) Wild type or  µMT KO mice (n = 5-9/group) were injected by LV::S or sham following the time line shown in (A), then pretreated with Ad5::hACE2 4 days before challenge with the ancestral SARS-CoV-2 strain. Lung viral RNA contents were determined at 3 dpi. Data information: Statistical significance was evaluated by Mann-Whitney test (*= p < 0.05, **= p < 0.01, ****= p < 0.0001).",
    "ncbi_link": "hACE2: 59272"
  },
  {
    "caption": "survival curves (G) of Cre+ or TKO mice injected subcutaneously with B16F10 OVA cells (n = 7 per genotype). Survival time was defined as the time required for a tumor to reach a volume of 500 mm3.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(J) Representative plots (left panels) and quantification (right panels) of IFNγ- and TNFα-producing CD8 TILs of B16F10 OVA tumors from Cre+ (n = 10) and TKO (n = 12) animals at day 14.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(F) Oxygen consumption rate of Cre+ (n = 8 mice) or TKO (n = 7 mice) CD8 T cells activated ex vivo as in B after mitochondrial stress test analysis. Two representative WT and TKO animals are shown (left panel); the corresponding quantification for basal and maximum respiration is shown (right panels). Values are normalized to basal Cre+ measurements. T cells were isolated as in A.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(C) qPCR of Cpeb4 mRNA in CD8 T cells resting or activated ex vivo with CD3/CD28/IL-2 at the indicated time-points; Tbp is used as endogenous control (n = 5 mice). CD8 T cells were isolated from the spleen and lymph nodes from WT mice.",
    "ncbi_link": "Cpeb4: 67579
Tbp: 21374"
  },
  {
    "caption": "(D) qPCR analysis of Atf4, Ddit3, Xbp1s and Hspa5 mRNA levels in Cpeb4+/+ (n = 5) and Cpeb4-/- (n = 6) CD8 cells activated as in a; Tbp is used as endogenous control (n = 5).",
    "ncbi_link": "Atf4: 11911
Cpeb4: 67579
Ddit3: 13198
Hspa5: 14828
Tbp: 21374
Xbp1s: 22433"
  },
  {
    "caption": "(F) Ddti3 mRNA levels in CD8 T cells from B16F10 tumors and spleen of WT (n=8) and TKO (n=10) mice. The data are shown as ratio between tumors and spleen.",
    "ncbi_link": "Ddti3: 13198"
  },
  {
    "caption": "(G) Flow cytometry analysis of apoptotic AnnexinV+ Cre+ (n = 4) or TKO (n = 6) CD8 cells activated as in A.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(A) Western blot of CPEB4 in input and immunoprecipitated fractions using anti-CPEB4 antibody of Cpeb4+/+ and Cpeb4-/- CD8 T cells activated ex vivo with CD3/CD28/IL-2 for 48 h; β-actin is used as control (n = 3).",
    "ncbi_link": "Cpeb4: 67579"
  },
  {
    "caption": "(D) RIP-seq data from several 3′ UTRs depicting normalized RIP-seq coverage for inputs (light grey and blue) and IP (dark grey and blue) from Cpeb4+/+ and Cpeb4-/- CD8 T cells. Image obtained using the integrated genome viewer (IGV).",
    "ncbi_link": "Cpeb4: 67579"
  },
  {
    "caption": "(E) Western blot (left panel) and quantification (right panel) of DDIT4 protein levels in Cre+ and TKO CD8 T cells activated as in A; β-actin is used as loading control (n = 7). (F) Western blot (left panel) and quantification (right panel) of HERPUD2 protein levels in Cre+ and TKO CD8 T cells activated as in A; β-actin is used as loading control (n = 8).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(G) Basal oxygen consumption rate (left panel) and maximal oxygen consumption rate (right panel) after mitochondrial stress test analysis. Cre+ and TKO CD8 T cells were activated as in A, but were treated with either Tauroursodeoxycholic Acid (TUDCA, T) 250 μM or vehicle for the last 24 h. Values are normalized to basal Cre+ measurements. n = 7 for all conditions in basal respiration; n = 6 for all conditions in maximal respiration.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(I) Quantification of IFNγ+ CD8 cells activated and treated as in G (n = 9 for Cre+ and n = 12 for TKO in both conditions). *P = 0.0168, ** P = 0.0014 for Cre+ vs. TKO, P = 0.0029 for Cre+ vs. Cre+ TUDCA, **** P <0.0001.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "A RNA-seq. of freshly isolated, proliferating and differentiating satellite cells reveals an increased expression of linc-MYH in proliferating and differentiating MuSCs, but no expression is found in in freshly isolated MuSCs.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "Expression of linc-MYH is confined to skeletal muscle in mouse (B) tissues.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "Expression of linc-MYH is confined to skeletal muscle in human (C) tissues.",
    "ncbi_link": "linc-MYH: "
  },
  {
    "caption": "D Expression of linc-MYH is not detected in limb buds at E10.5 (n = 3), E13.5 (n = 3) and E15.5 (n = 3). Expression of linc-MYH in hindlimb muscle of E18.5, newborn and 7 day old animals (n = 3/3/3). Expression of linc-MYH in m. soleus (soleus), m. tibialis anterior (TA) and and m. extensor digitorum longus (EDL) muscle at 3 weeks (n = 3) and 8 weeks of age (n = 5). Biological replicates were used for all PCR experiments, data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "E Murine linc-Myh is localized in nuclear extracts of C2C12 cells. Xist (nuclear) and Gapdh (mainly cytoplasmic) were used as controls (n = 2 nuclear / 3 cytoplasmic biological replicates.) Data are mean ± S.E.M.",
    "ncbi_link": "Gapdh: 
Xist: 
linc-Myh: 74184"
  },
  {
    "caption": "F-H RNA-FISH identifies linc-Myh in nuclei (DAPI, blue) of C2C12 myoblasts. (G) Adipor (cytoplasmic) and (H) Xist (nuclear) were used as controls.",
    "ncbi_link": "Adipor: 
Xist: 
linc-Myh: 74184"
  },
  {
    "caption": "(J) Heat map of proteins pulled down in the same experiments as in I, demonstrating that INO80 chromatin remodeler complex exclusively interacts with linc-MYH. Blue color indicates pull-down of the respective protein, white color indicates that the protein was not detected in the respective sample.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "Body weight (A) of male linc-MYH KO and ctrl mice at 10 weeks (n = 24 KO/17 WT; Student's t test, two-tailed, **p < 0.01)",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "tibia length (B) of male linc-MYH KO and ctrl mice of 10 weeks (n = 9 KO/13 WT; Student's t test, two-tailed, not significant). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "C, D Weight of m. tibialis anterior (TA) and m. digitorum longus (EDL) of male linc-MYH KO and ctrl mice at 10 weeks (n = 9 KO/10 WT for TA, n = 10 KO/11 WT for EDL; Student's t test, two-tailed, **p < 0.01, ***p<0.001). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "Size distribution of fibers in cross sections of TA (E, F) and EDL (G, H) muscle in male linc-MYH KO (blue) and ctrl (grey) animals at 10 weeks. A significant increase of fiber size was observed for TA and EDL muscles of linc-MYH KO mice (n = 5 KO/4 WT for TA, n = 3 KO/3 WT for EDL muscle, two-way ANOVA with Fisher's multiple comparisons; *p < 0.05, **p < 0.01; > 250 fibers per animal were counted). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "Size distribution of fibers in cross sections of TA and EDL muscle in male linc-MYH KO (blue) and ctrl (grey) animals at 10 weeks. A significant increase of fiber size was observed for TA and EDL muscles of linc-MYH KO mice (n = 5 KO/4 WT for TA, n = 3 KO/3 WT for EDL muscle, two-way ANOVA with Fisher's multiple comparisons; *p < 0.05, **p < 0.01; > 250 fibers per animal were counted). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "L-O Number of myonuclei / fiber and of Pax7pos (red) MuSCs (red arrows) on myofibers isolated from flexor digitorum brevis muscle. Nuclei were stained using DAPI (blue). Scale bar in L indicates 50 µm for L and M. (N) The number of myonuclei / isolated fiber is increased in linc-MYH KO compared to WT myofibers (n = 4 KO/4 WT, > 26 fibers/animal; Mann-Whitney test two-tailed, * p < 0.05). (O) Number of MuSCs on isolated fibers from linc-MYH KO and WT mice (n = 4 KO/4 WT animals, Mann-Whitney test two-tailed; ****p < 0.0001). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "P-S Number of Pax7 (red) positive MuSCs in cross sections of tibialis anterior muscle (P-R); the relative amount of quiescent MuSCs identified by double staining (yellow arrows) for Pax7 and CalcR (green) does not significantly differ between WT and linc-MYH KO animals (S). Nuclei were stained with DAPI (blue). Scale bar in P indicates 25 µm for P and Q. (n = 3 KO/3 WT animals, Mann-Whitney test one-tailed; *p = 0.05, ns: not significant). All data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "T The number of MuSC-related events in FACS experiments is significantly increased in linc-MYH-KO animals (n = 7 KO/7 WT, Student's t test, two-tailed, *p = 0.0126). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "U-V Structure of MuSCs and the heterochromatin content of MuSC nuclei is not changed in linc-MYH KO (V) compared to WT mice (U).",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "RNA in situ hybridization proximity ligation assay (rISH-PLA) detects the close proximity of a specific RNA with proteins in situ modified from Roussis et al.. (B-C) rISH-PLA confirms the proximity of linc-MYH to endogenous INO80-V5 in the nucleus of proliferating WT MuSCs (B). The specific signal is lost in linc-MYH deficient MuSCs (C). (n = 3 WT/3 KO biological replicates; Mann-Whitney test, *p = 0.05). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "E-I Representative images of TA muscle sections of 10 weeks old mice stained for PAX7 (green) and EdU incorporation (red). MuSCs without (green arrows) and with EdU-labeling (red arrows) are indicated. (E, F) Deletion of linc-MYH results in increased numbers of muscle stem cells and pronounced increase of the ratio of EdU-positive MuSCs. (G-I) The increase in both the number of MuSCs and EdU positive MuSCs in linc-MYH mutant muscle is abolished by constitutive (G: Pax7-Crepos / INO80-/-, Ino80 KO; H: linc-MYH-/- / Pax7-Crepos / INO80-/-, dKO) and induced (I: linc-MYH-/- / Pax7-CreERT2pos / INO80-/-, dKO CreERT) deletion of INO80 in Pax7 expressing cells.",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
ERT: 2099
ERT2: 2099
INO80: 68142
Ino80: 68142
Pax7: 18509"
  },
  {
    "caption": "Statistical evaluation of the number of muscle stem cells observed in TA muscles (J). ; (n = 5 WT/5 linc-MYH KO/4 Ino80 KO/5 dKO/3 CreERT dKO animals in J/K, n = 6 WT/6 linc-MYH KO/5 Ino80 KO/6 dKO/3 CreERT dKO animals in L **p < 0.01, ****p <0.0001, > 31 MSCs /animal in K; ANOVA test with multiple comparisons against WT. Sidak-Holm correction was used. Data are mean ± S.E.M.).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
ERT: 2099
Ino80: 68142"
  },
  {
    "caption": "Statistical evaluation of the ratio of EdU-incorporating MuSCs relative to all Pax7-positive MuSCs (K). ; (n = 5 WT/5 linc-MYH KO/4 Ino80 KO/5 dKO/3 CreERT dKO animals in J/K, n = 6 WT/6 linc-MYH KO/5 Ino80 KO/6 dKO/3 CreERT dKO animals in L **p < 0.01, ****p <0.0001, > 31 MSCs /animal in K; ANOVA test with multiple comparisons against WT. Sidak-Holm correction was used. Data are mean ± S.E.M.).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
ERT: 2099
Ino80: 68142"
  },
  {
    "caption": "Statistical evaluation of the number of myonuclei in myofibers of TA muscles from different genotypes (L) (n = 5 WT/5 linc-MYH KO/4 Ino80 KO/5 dKO/3 CreERT dKO animals in J/K, n = 6 WT/6 linc-MYH KO/5 Ino80 KO/6 dKO/3 CreERT dKO animals in L **p < 0.01, ****p <0.0001, > 31 MSCs /animal in K; ANOVA test with multiple comparisons against WT. Sidak-Holm correction was used. Data are mean ± S.E.M.).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
ERT: 2099
Ino80: 68142"
  },
  {
    "caption": "A-D Isolated linc-MYH KO MuSCs reach confluence much faster than WT MuSCs indicating higher proliferation rates. Deletion of INO80 eliminates the difference between Pax7-Crepos / INO80-/- (Ino80 KO) and linc-MYH-/- / linc-MYH-/-/ Pax7-Crepos / INO80-/- (dKO). Images are representative images for cultures after 13 days in culture.",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Ino80: 68142
Pax7: 18509"
  },
  {
    "caption": "E Differences in proliferation rates are abolished by additional deletion of INO80 in MuSCs. Cell confluence was monitored by a live cell imaging analysis system for 13 days (n = 7 WT / 6 linc-MYH KO / 3 Ino80 KO / 3 dKO independent preparations of MuSCs).",
    "ncbi_link": "linc-MYH: 74184
INO80: 68142
Ino80: 68142"
  },
  {
    "caption": "F Statistical analysis of cell confluence after 13 days of muscle stem cell proliferation (n = 7 WT / 6 linc-MYH KO / 3 Ino80 KO / 3 dKO independent preparations of MuSCs, Student's t test, two-tailed; *p < 0.05, ns = not significant). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184
Ino80: 68142"
  },
  {
    "caption": "G-I Gene set enrichment analysis (GSEA, broadinstitute.org) of microarray data from proliferating MuSCs. Comparison of linc-MYH-/- vs. WT proliferating MuSC transcriptomes shows enrichment of genes related to cell proliferation (G), enrichment of genes containing cis regulatory elements for YY1 (H) and p53 (I). Enrichments are highly significant using the most conservative familywise-error rate method (FWER). Enrichments were lost in linc-MYH-/- MuSCs after additional deletion of INO80 (dKOs) compared to Pax7-Crepos / INO80-/- MuSCs.",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "Heat maps of the 10 most upregulated genes of the respective gene sets depicted in G-I in linc-MYH-/- vs. WT MuSCs and in linc-MYH-/-/ Pax7-Crepos / INO80-/- dKO vs. Pax7-Crepos / INO80-/- MuSCs. Expression of up-regulated genes in linc-MYH-/- was normalized after additional deletion of INO80 (dKOs), indicating that effects of linc-MYH completely depend on INO80 (WT n = 4, linc-MYH-/- n = 4, Pax7-Crepos / INO80-/- n = 4, Pax7-Cre dKO n = 3 animals used for independent isolations of MuSCs).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "Heat maps of the 10 most upregulated genes of the respective gene sets depicted in G-I in linc-MYH-/- vs. WT MuSCs and in linc-MYH-/-/ Pax7-Crepos / INO80-/- dKO vs. Pax7-Crepos / INO80-/- MuSCs. Expression of up-regulated genes in linc-MYH-/- was normalized after additional deletion of INO80 (dKOs), indicating that effects of linc-MYH completely depend on INO80 (WT n = 4, linc-MYH-/- n = 4, Pax7-Crepos / INO80-/- n = 4, Pax7-Cre dKO n = 3 animals used for independent isolations of MuSCs).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "Heat maps of the 10 most upregulated genes of the respective gene sets depicted in G-I in linc-MYH-/- vs. WT MuSCs and in linc-MYH-/-/ Pax7-Crepos / INO80-/- dKO vs. Pax7-Crepos / INO80-/- MuSCs. Expression of up-regulated genes in linc-MYH-/- was normalized after additional deletion of INO80 (dKOs), indicating that effects of linc-MYH completely depend on INO80 (WT n = 4, linc-MYH-/- n = 4, Pax7-Crepos / INO80-/- n = 4, Pax7-Cre dKO n = 3 animals used for independent isolations of MuSCs).",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "A-D γ-H2AX staining of proliferating MuSCs from WT (A), linc-MYH deficient (B), Pax7-Crepos / INO80 KO (C), and linc-MYH/INO80 dKO (D) mice. Deletion of INO80 results in increased γ-H2AX signals while deletion of linc-MYH has no effects (asterisk: low γ-H2AX signals, arrow: γ-H2AX-foci detected in nuclei, arrowhead: pan-nuclear γ-H2AX signal.",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "H-I Gene set enrichment analysis of microarray data obtained for proliferating MuSCs shows enrichment of genes related to activity of ATR in response to replication stress recovery (H) and enrichment of genes involved in chromosome maintenance (I) in WT compared to Pax7-Crepos INO80-/- MuSCs. Enrichment of these or similar gene sets was not observed when comparing WT to linc-MYH-/- MuSCs.",
    "ncbi_link": "linc-MYH: 74184
Cre: 2777477
INO80: 68142
Pax7: 18509"
  },
  {
    "caption": "A, B Co-Immunoprecipitation of INO80 complex subunits from TA muscles of WT and linc-MYH KO mice followed by Western Blot analysis. (B) Statistical analysis of Co-IP/Western Blot data. The amount of RUVBL1 and RUVBL2 in the INO80 complex is not changed after deletion of linc-MYH, while the amounts of YY1, WDR5 and TFPT pulled down by INO80 increase (n = 3 WT / 3 linc-MYH KO animals; one-way ANOVA, multiple comparisons by Fishers LSD test, *p<0.05). Data are mean ± S.E.M.",
    "ncbi_link": "linc-MYH: 74184"
  },
  {
    "caption": "(A) Coimmunoprecipitation of SMO-HA and Myc-Smaug proteins. Extracts of Cl8 cells expressing combinations of SMOWT-HA or SMOPKA-SD-HA with Myc-SmaugWT in the absence or presence of HH were immunoprecipitated (IP) with anti-HA. The input (lower panel) and the IP complexes (upper panel) were analyzed by western blot with anti-Myc (αMyc) or anti-HA (αHA) antibodies. Here and in the other figures, the names of the proteins detected are indicated on the left and the molecular weights on the right, in kDa; the samples loaded for the input and the supernatants are equivalent to a tenth of the volume loaded for the IPs. * corresponds to higher molecular weight forms of SMO of unknown origin. Here and in panel F, the black arrow indicates unphosphorylated SMOWT-HA and the bracket indicates the phosphorylated forms of SMOWT-HA or SMOPKA-SD.",
    "ncbi_link": "Myc: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(D, E) Mapping of the Smaug interaction domain in SMO. Extracts from Cl8 cells transfected with Myc-SmaugWT and various regions of SMO fused to either HA (D) or to GFP (E) were immunoprecipitated with αMyc (D) or αGFP (E) and analyzed by western blotting with αMyc (lower panel in D and upper panel in E), αHA (D, upper panel) or αGFP (E, lower panel). In: Input; Sup: supernatant. See also Fig EV1D-F.",
    "ncbi_link": "GFP: 
Myc: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(F) Hyperphosphorylated forms of SMO do not interact with Smaug. Left panel: Extracts of Cl8 cells expressing SMOWT-HA with or without Myc-SmaugWT, in the absence or presence of HH were IP with an αMyc antibody before analysis by western blot with αHA (upper panel) or αMyc antibodies (lower panel). Right panel: Cl8 cells expressing SNAP-SMOWT with Myc-SmaugWT in the presence of HH were extracellularly labelled with a membrane-nonpermeable fluorescent SNAP substrate before cell lysis and immunoprecipitation (IP) with anti-Myc. Labelled SNAP-SMO was directly visualized after electrophoresis. Note its presence in the IP fraction with a relative enrichment of the less phosphorylated forms compared to the hyperphosphorylated forms. See also Fig EV1G-J.",
    "ncbi_link": "Myc: 
SNAP: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(G) SMO and Smaug colocalize. Representative fluorescent images of Cl8 cells expressing GFP-SmaugWT alone (1-2) or together with SMOWT-mCherry (3-3'' and 4-4'') either without (1, 3-3") or with HH (2, 4-4"). The merge images in 3" and 4" show GFP-SmaugWT in green and SMOWT-mCh in red. The same results were seen with different fluorescent tags as well (Fig EV2B). The lack of effect of HH on GFP-SmaugWT in absence of SMOWT-mCh is likely due to limiting amounts of endogeneous SMO. A least 20 cells were assayed for each condition. In absence of HH, all co-transfected cells exhibited greater than 90% colabelled SMOWT-mCherry. Scale bar (shown in G1, identical for all panels):10μm. See also Fig EV2.",
    "ncbi_link": "GFP: 
mCherry: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(B, C) Smaug downregulates reporter expression. Mean values of the relative levels of SNAP-GUS reporter (SNAP-GUS/GFP-SNAP ratio, in arbitrary units) in extracts of transfected Cl8 cells in the absence (black) or presence of λN-SNAP-Smaug (red), λN-SNAP (pale grey) or SNAP-Smaug (dark grey). See Fig EV3A for the representative gel and Fig EV3B which shows that λN-SNAP-Smaug has no effect on a SNAP-GUS construct that lacks the 5BoxB. N=3 (biological replicates). See also Fig EV3A-C. Here and in D-F: SNAP-GUS/GFP-SNAP ratios were set to 1 in cells expressing λN‐SNAP-Smaug. The error bars correspond to the standard deviation of the mean (SD). Statistical analysis was done by a Kruskal-Wallis test by ranks followed by a Dunn test and p values are: black bracket <0.05, red bracket <0.01, green bracket <0.0001. Here and in D-E: 15 ng of pAct.λN-SNAP-smaug plasmid were used per transfection.",
    "ncbi_link": "5BoxB: 
Act: 
SNAP: 
smaug: 39034"
  },
  {
    "caption": ", E) HH/SMO reduces Smaug levels and its overall negative effect on reporter expression. Mean values of the relative levels of reporter expression (determined as above) (D) or of λN-SNAP-Smaug (ratio λN-SNAP-Smaug/GFP-SNAP) (E) in the absence of SMO constructs (red) or in the presence of SMOWT-HA (green), SMOPKA-SD-HA (blue) or SMO∆958-HA (yellow), without HH (plain boxes) or in presence of HH (striped boxes). N=6 (independent biological replicates), except for \"no SMO, no HH\" and \"SMOWT with HH\" conditions where n=10 (independent biological replicates). A representative gel is shown in Fig EV3D. Note that SMOWT-HA or HH alone had reproducible weak effects that were observed in two independent biological triplicates but were not statistically significant. See also Fig EV3E-F.",
    "ncbi_link": "SMO: 33196"
  },
  {
    "caption": "(F) HH/SMO reduces Smaug's intrinsic repressive ability. A similar experiment was conducted with different amounts of λN-SNAP-smaug expressing plasmid (ranging from 0 to 50 ng) as indicated). The mean values of the relative levels of reporter (y-axis) are plotted against the relative levels of λN-SNAP-Smaug (x-axis). SNAP-GUS/GFP-SNAP ratios were set to 1 in cells expressing λN‐SNAP-Smaug in absence of SMOPKA-SD/HH. The colored area represent the extent of the values observed for the relative amounts of reporter expression obtained with (blue) and without (red) SMOPKA-SD/HH, respectively. N=3 (biological triplicates). See Fig EV3H and also a representative gel in Fig EV3G.",
    "ncbi_link": "SNAP: 
λN: 2703540
smaug: 39034
Smaug: 39034"
  },
  {
    "caption": "(A) HH/SMO promotes slow-migrating forms of Smaug. Western blot analysis of Cl8 cells that transiently express HA-SmaugWT alone, or together with either SMOWT-GFP or SMOPKA-SD-GFP, in the presence or in absence of HH. GMAP serves as a loading control. Here and in the other panels, the antibodies used are indicated on the left. Here and in (B,C), the black arrows indicate the unphosphorylated form of HA-SmaugWT and the brackets indicate the slower migrating phosphorylated forms of HA-SmaugWT. NT: not transfected. See a phosphatase assay in Fig EV4A.",
    "ncbi_link": "GFP: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(B) Smaug phosphorylation requires its interaction with SMO. Western blot analysis of Cl8 cells expressing HA-SmaugWT, in presence of HH, in combination with SMO∆958-GFP, SMOPKA-SD-GFP or SMOPKA-SD, ∆978-GFP, as indicated.",
    "ncbi_link": "GFP: 
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(C) FU controls Smaug phosphorylation. Extracts of Cl8 cells expressing SNAP-Smaug with SMOPKA-SD FU-SD-GFP (with HH) in combination with GFP-FUWT, GAP-GFP-FUWT, Myc-FUEE or GAP-null-FUDANA (as indicated) were labeled for the SNAP tag before electrophoresis. After quantification of the gels, the percentage (%) of phosphorylated Smaug (% of phosphorylated forms of SNAP-Smaug total amounts of SNAP-Smaug) was estimated. In C to E, the mean values and (SD) for independent biological triplicates (N=3) are shown in the graph at the bottom, and the statistical analysis was done by one tailed bivariate Wilcoxon rank test. See also fig EV4C, D.",
    "ncbi_link": "GFP: 
Myc: 
SNAP: 
FU: 32855
GAP: 2596
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(D) Phosphorylation of Smaug by activated FU requires the co-expression of SMO. Mean values of the percentage of phosphorylated Smaug in extracts of Cl8 cells that express λN-SNAP-Smaug with GAP-GFP-FUWT and SMOWT alone or together (as indicated) N=3 (billogical triplicates). Note that the effect of GAP-GFP-FUWT and SMOWT together is lower than the one observed with GAP-GFP-FUWT and SMOPKA-SD FU-SD-GFP together (in panel C). This could have multiple nonexclusive causes, including the fact that SMOWT is present at much lower levels than SMOPKA-SD FU-SD [38] and/or the involvement of another kinase. See also Fig EV4B. Note that Smaug does not coIP FU unless SMO is present see Appendix Figure S2.",
    "ncbi_link": "GFP: 
SNAP: 
FU: 32855
GAP: 2596
λN: 2703540
Smaug: 39034
SMO: 33196"
  },
  {
    "caption": "(E) Forcing the interaction of Smaug with activated FU leads to a SMO-independent phosphorylation of Smaug. Mean values of the percentage of phosphorylated Smaug in Cl8 cells coexpressing λN-SNAP-Smaug with GFP-FU, FU-SBR, FUEE-SBR or FUDANA-SBR, with or without HH, as indicated. N=3 (biological triplicates). See also Fig EV4C and D. Note that the levels of Smaug phosphorylation observed in presence of FUDANA-SBR are not lower than those seen with GFP-FU. This suggests an incomplete inhibition of endogenous FU, which may be due to the trapping of FUDANA-SBR by Smaug. See a representative blot in Fig EV3C and a phosphatase assay in Fig EV4D.",
    "ncbi_link": "GFP: 
SNAP: 
FU: 32855
λN: 2703540
Smaug: 39034"
  },
  {
    "caption": "(A and C) Effect of FUEE-SBR on Smaug phosphorylation and levels. Extracts of Cl8 cells transfected with λN-SNAP-smaug (25 ng) and SNAP-GUS-5BoxB (300 ng) plasmids in absence or with different amounts of FUEE expressing plasmid (ranging from 15 to 60 μg, as indicated) were analyzed by electrophoresis before quantification as above. See a reprenstive gel in Fig EV5A. The % of phosphorylated SNAP-Smaug protein (determined as in Fig 3) (A) are represented as a function of the levels of FUEE-SBR. The mean values and (SD) for independent biological triplicates (N=3) are shown in the graph at the bottom. The statistical analysis was done by one tailed bivariate Wilcoxon rank test with a p value= 0.05 (*). Here CLIP-GUS was used as an internal control.",
    "ncbi_link": "5BoxB: 
GUS: 
SNAP: 
FU: 32855
λN: 2703540
smaug: 39034"
  },
  {
    "caption": "(B) Effect of FUEE-SBR on Smaug activity. The relative levels of reporter expression obtained in the same experiment as in (A-C) are represented as a function of the % of phosphorylated Smaug. Color of data points correspond to ng of transfected FUEE-SBR in A-C.",
    "ncbi_link": "FU: 32855"
  },
  {
    "caption": "(A and C) Effect of FUEE-SBR on Smaug phosphorylation and levels. Extracts of Cl8 cells transfected with λN-SNAP-smaug (25 ng) and SNAP-GUS-5BoxB (300 ng) plasmids in absence or with different amounts of FUEE expressing plasmid (ranging from 15 to 60 μg, as indicated) were analyzed by electrophoresis before quantification as above. See a reprenstive gel in Fig EV5A. The relative levels of of λN-SNAP-Smaug protein (C) (determined as in Fig 2) are represented as a function of the levels of FUEE-SBR. The mean values and (SD) for independent biological triplicates (N=3) are shown in the graph at the bottom. The statistical analysis was done by one tailed bivariate Wilcoxon rank test with a p value= 0.05 (*). Here CLIP-GUS was used as an internal control.",
    "ncbi_link": "5BoxB: 
GUS: 
SNAP: 
FU: 32855
λN: 2703540
smaug: 39034"
  },
  {
    "caption": "(D) Effect of FUEE-SBR on Smaug subcellular localization.Representative fluorescent images of Cl8 cells expressing GFP-SmaugWT (1), FUEE-SBR-mCherry (2), FUDANA-SBR-mCh (3) or expressing GFP-SmaugWT together with FUEE-SBR-mCherry (4-4'') or GFP-SmaugWT together with FUDANA-SBR-mCh (5-5''). The merge images in 4" and 5" show GFP-SmaugWT in green and FUEE-SBR-mCh or FUDANA-SBR-mCh in red. (6) In presence of FUEE-SBR, 274 of a total of 294 cotransfected cells show a diffuse localization of Smaug and FU and no foci. In presence of FUDANA-SBR, 100% of the cotransfected cells (n=241) show Smaug and FU distributed in bodies and colocalized. 250 ng of plasmid were used for each construct. Scale bar (shown in D1, identical for all panels): 10μ",
    "ncbi_link": "GFP: 
mCh: 
mCherry: 
FU: 32855
Smaug: 39034"
  },
  {
    "caption": "(A) Effect of FUEE-SBR and HH/SMO on endogeneous Smaug target mRNAs in Cl8 cells. Relative mRNA levels estimated using semi-quantitative RT-PCR for various Smaug's targets in Cl8 cells expressing FUEE-SBR (black) , FUEE (dark grey) , or FUDANA-SBR (light grey) were reported with respect to levels of a GFP control. mRNA levels were set to 1 for the GFP control. The list of genes and the sequences of the primers used are shown in Appendix Table S2 and S3. See also Fig EV5E. Here and in Fig EV5D: RNA encoding mitochondrial proteins are written in blue. N=3 (biological triplicates) and the quantifications were repeated 3 times on each sample.The results are presented as the means ± standard error. The differences between groups were assessed using Student's t-tests with Prism V8.2.1 software. A p value <0.05 was considered to indicate a statistically significant difference",
    "ncbi_link": "FU: 32855
SMO: 33196"
  },
  {
    "caption": "(B) Effect of HH on endogeneous targets of Smaug in the wing imaginal disc. Relative levels of Smaug's targets mRNAs in MS1096; UAS-hh or hhts and their respective controls (as in Fig EV5X). N=3, with xx disc for each phenotype.",
    "ncbi_link": "MS1096: 
hh: 42737
UAS: 5658215///5658214
Smaug: 39034"
  },
  {
    "caption": "(C) Effect of smaug mutation on [fu1] wing class distribution. Percent distribution of phenotypic classes (defined in Appendix Figure S4) in fu1 males in presence of zero (fu1), one (fu1;;smaug47/+) or two copies (fu1;; smaug47/smaug47) of the smaug47 allele. The wings were double-blindly classified in "weak" and "strong" according to the LV3-V4 defects (see Fig EV6B). *Chi2 statistical analysis gave a p of 0,015 for fu1 and fu1;;smaug47/+ distributions and of 0,0024 when comparing fu1;;smaug47/+ to fu1;; smaug47/smaug47.",
    "ncbi_link": "fu: 32855
smaug: 39034"
  },
  {
    "caption": "Flow cytometry analysis of PD-L1 after gemcitabine and RT (as described above) in KPC (E) and Pan02 (F) following Stat1 downregulation by siRNA (mean ± SD, n=3, Student's t-test). MFI, mean fluorescence index;",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "B. Representative two-dimensional IFT-tracks from WT, kinesin-II (klp-11), and osm-3 null animals. Red and violet circles indicate the start and end of the tracks, respectively. Proteins used for tracking experiments are CHE-3 tagged with 7x GFP, or DYF-11 tagged with 3x GFP.",
    "ncbi_link": "kinesin-II: 177685
klp-11: 177685
osm-3: 177141"
  },
  {
    "caption": "B. Representative two-dimensional IFT tracks from WT and OSM-3(1 or 3xGS) animals. Red and violet circles indicate the start and end of the tracks, respectively.",
    "ncbi_link": "OSM-3: 177141"
  },
  {
    "caption": "A. Histogram of anterograde IFT speeds of 3xGFP::CHE-3 at the middle (top) and distal (bottom) ciliary segments (top). Comparisons were performed between the WT and osm-3 mutants. ***",
    "ncbi_link": "osm-3: 177141"
  },
  {
    "caption": "B. Schematic depiction of the C. elegans amphid and phasmid cilia. Each cilium contains a ciliary base, a middle segment (m.s.), and a distal segment (d.s.). C. Amphid (top) and phasmid (bottom) cilia in the WT and osm-3 GS knock-in animals. Cilia are marked with 7xGFP::CHE-3. Arrowheads indicate the ciliary base. Arrows indicate the junctions between the middle and distal segments.",
    "ncbi_link": "osm-3: 177141"
  },
  {
    "caption": "D. Cilium length (mean ± SD) in WT and osm-3 mutant animals. Comparisons were performed between the WT and osm-3 mutants.",
    "ncbi_link": "osm-3: 177141"
  },
  {
    "caption": "E. Quantifications of dye-filling defects from WT and osm-3 mutant animals.",
    "ncbi_link": "osm-3: 177141"
  },
  {
    "caption": "F. Representative TEM images of the middle ciliary segments from osm-3(1xGS) and osm-3(3xGS) worms. Red arrowheads indicate ectopic singlet microtubules. Blue arrowheads indicate ectopic doublet microtubules. The schematics below depict the phenotype of each image.",
    "ncbi_link": "osm-3: 177141"
  },
  {
    "caption": "Parkin expression in iBAT from mice exposed to cold (4ºC) for 1 day (1d) or 21 days (21d) compared with control mice (ctl) maintained at 22ºC. Left: Relative transcript levels. Right: representative immunoblot and Parkin protein quantification. Ponceau staining (PS) was used as loading control. (n=6; transcript levels) (n=3; protein levels). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, cold vs. control and ##p<0.01, 1d vs. 21d. One-way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Relative transcript levels of Park2 in sWAT and eWAT. (n= 6). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, cold vs. control and ###p<0.001, 1d vs. 21d. One-way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "Relative transcript levels of Parkin in iBAT, sWAT and eWAT of mice injected with the β3-AR agonist CL316,243, every day for 1 week. (n=6). Data are presented as means ±s.e.m. *p<0.05, ***p<0.001, CL316,243 treatment vs. saline. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Relative transcript levels of Park2 and Ucp1 in mature brown adipocytes compared with the stromal vascular fraction (SVF) in iBAT. (n=3). Data are presented as means ±s.e.m. **p<0.01, ***p<0.001. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "mRNA expression profiles of Park2 and Ucp1 during differentiation. (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, ***p<0.001 compared to day (d) 4. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "Relative transcript levels of Park2 and Ucp1 in brown adipocytes in culture with fetal bovine serum (FBS, to trigger in vitro differentiation) or charcoal-stripped serum (CSS, non-permissive for differentiation). (n=3). Data are presented as means ±s.e.m. **p<0.01, ***p<0.001. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "Relative transcript levels of Park2 and Ucp1 in brown adipocytes in culture treated with norepinephrine (NE) or cAMP for indicated times. (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, ***p<0.001 compared to non-treated cells. One-way ANOVA with Dunnett's post hoc test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "Relative transcript levels of Park2 in brown adipocytes treated with NE in the presence or absence of cycloheximide (CHX). (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, ***p<0.001. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "Relative mRNA expression levels of Parkin in brown adipocytes treated with NE in the presence or absence of actinomycin D (n=3). Data are presented as means ±s.e.m. One-way ANOVA with Tukey's post hoc test comparing treatments.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Park2 gene promoter activity in HIB-1B cells transfected with a pGL4-Park2-Luc reporter construct treated with or without NE or cAMP. Data was normalized using Renilla luciferase activity and are expressed as the relative firefly luciferase activity compared to that in untreated cells. (n=6). Data are presented as means ±s.e.m. *p<0.05 compared to non-treated cells. ANOVA with Dunnett's post hoc test",
    "ncbi_link": "Luc: 
Park2: 50873"
  },
  {
    "caption": "Relative transcript levels of Park2 and Ucp1 in brown adipocytes treated with cAMP (12 h) plus H89 (a PKA inhibitor) or SB202190 (a p38 MAPK inhibitor). (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01 with vs. without inhibitor and #p<0.05, and ##p<0.01, ###p<0.001 with vs. without cAMP. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "Relative transcript levels of Park2, and concentration of glycerol in the culture medium of brown adipocytes treated with cAMP (24h) plus Atglistatin (an adipose triglyceride lipase inhibitor) or CAY10499 (a hormone sensitive lipase inhibitor). (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01 ***p<0.001 with vs. without inhibitor and #p<0.05, and ##p<0.01, ###p<0.001 with vs. without cAMP. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "Relative transcript levels of Park2 and Ucp1 in brown adipocytes treated for 24h with a PPARα activator (GW7647), a PPARα inhibitor (GW6471) with or without norepinephrine (NE), or all-trans-retinoic acid (RA). (n=3). Data are presented as means ±s.e.m. *p<0.05, **p<0.01 ***p<0.001. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Ucp1: 22227"
  },
  {
    "caption": "Relative transcript levels of Park2 in wild-type and PPARα-KO brown adipocytes treated for 24h with NE (n=3). Data are presented as means ±s.e.m. *p<0.05. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "PPARα: 19013
Park2: 50873"
  },
  {
    "caption": "Park2 gene promoter activity in HIB-1B cells transfected with a pGL4-Park2-Luc reporter construct and, when indicated, with a pSG5-Ppara expression vector. Cells were treated with the PPARα activator GW7647 or NE. Data was normalized using Renilla luciferase activity and are expressed as the relative firefly luciferase activity compared to that only transfected with the pGL4-Park2-Luc construct (n=6). Data are presented as means ± s.e.m. *p<0.05 compared to non-treated cells. ANOVA with Dunnett's post hoc test.",
    "ncbi_link": "Luc: 
Ppara: 19013
Park2: 50873"
  },
  {
    "caption": "Left: Representative optical microscopic images of H&E-stained iBAT (scale bars, 110µm) and electron microscopic images of iBAT (scale bars, 20µm) from wild-type (WT) and Parkin-KO (KO) mice. Right: Quantification of lipid droplet area from electron microscopic images (10 images per condition were used, n =3 WT, n=3 Parkin-KO). Data are presented as means ±s.e.m. *p<0.05. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Relative transcript levels of thermogenesis-related genes of iBAT from WT and Parkin-KO mice exposed to acute cold (4ºC, 24h) compared to those maintained at the control temperature (22ºC). (n=8; WT) (n=6; Parkin-KO). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, ***p<0.001, CTL vs. cold; #p<0.05, WT vs. Parkin-KO. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Weight gain from WT and Parkin-KO mice fed with chow (CD) or high fat diet (HFD). (n=8; WT) (n=6; Parkin-KO).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": ", blood glucose levels and plasma insulin levels from WT and Parkin-KO mice fed with chow (CD) or high fat diet (HFD). (n=8; WT) (n=6; Parkin-KO).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "insulin tolerance test (ITT) from WT and Parkin-KO mice fed with chow (CD) or high fat diet (HFD). (n=8; WT) (n=6; Parkin-KO).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Relative transcript levels of thermogenesis-related genes in iBAT from WT and Parkin-KO mice given HFD. (n=8; WT) (n=6; Parkin-KO). Data are presented as means ±s.e.m. #p<0.05. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Relative transcript levels of Park2 in iBAT from WT mice fed CD or HFD. (n=8; WT) (n=6; Parkin-KO). Data are presented as means ±s.e.m. Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Park2: 50873
Parkin: 50873"
  },
  {
    "caption": "WT mice were acclimated to cold for 21 days (21d, 4ºC) and then deacclimated at thermoneutrality (29ºC) for 1 day (1d) or 7 days (7d). Relative transcript levels of thermogenesis-related genes and Park2 in iBAT. (n=6). Data are presented as means ±s.e.m. *p<0.05, **p<0.01, ***p<0.001 compared to 21d. ANOVA with Dunnett's post hoc test.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Representative immunoblot of LC3B in iBAT, and the loading control (Ponceau staining, PS).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Immunoblot for p62 and OPTN (left) and its quantification (right) in iBAT. PS was used as the loading control. Arrowhead indicates p62 band and asterisk indicates a non-specific band. (n=4; cold) (n=3; deacclimation). Data are presented as means ±s.e.m. **p<0.01. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Quantification of the total protein amounts of the indicated OXPHOS protein subunits and UCP1 in iBAT. (n=4; cold) (n=3; deacclimation). Data are presented as means ±s.e.m. *p<0.05. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Citrate synthase activity in iBAT protein extracts. (n=6; WT) (n=8; Parkin-KO). Data are presented as means ±s.e.m. *p<0.05. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Mitochondrial DNA (mtDNA) content in iBAT relative to nuclear DNA (nDNA). (n=6; WT) (n=8; Parkin-KO). Data are presented as means ±s.e.m. *p<0.05. ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "Wild-type (WT) and Parkin-KO (KO) mice were acclimated to cold for 21 days (c) and then deacclimated at thermoneutrality (29ºC) for 1 day (d). Representative electron microscopic images of mitochondrial integrity and autophagic/mitophagic events in iBAT after 1 day of cold-deacclimation. Yellow arrowheads indicate mitochondria cristae and blue arrowheads indicate double-membrane autophagosomes. Left panels scale bars, 2 µm. Right panels scale bars, 1 µm.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "B. Significant increase of survival in Ppt1-/- animals transplanted with HSCPs or BM isolated from Ppt1+/+ mice; Log-rank: HSPCs/BM+/+ tx vs BM-/- tx p<0.001; BM-/- tx vs Ppt1-/- UT p < 0.001.",
    "ncbi_link": "Ppt1: 19063"
  },
  {
    "caption": "D. Representative fluorescence microscope photomicrographs showing the distribution of donor-derived cells (transduced with D.NGFR reporter gene, red) and autofluorescent storage material (AF, green) in the brain of a Ppt1-/- mouse euthanized at 240 days of age, after transplantation with HSPCs isolated from Ppt1+/+ mice. Insets in D show high magnification representative confocal scanning photomicrographs of DNGFR+AF+ cells in different regions of the CNS. Arrows show DNGFR+ cells engulfed with autofluorescent (AF) storage material. Scale bar (main figure) = 1mm; scale bar (insets) = 25μm.",
    "ncbi_link": "D.NGFR: 
Ppt1: 19063"
  },
  {
    "caption": "G. Representative brightfield photomicrographs of Nissl-stained brain sections from wild type Ppt1+/+ mice and untreated or transplanted Ppt1-/- mice. Black dashed box highlights a portion of the cortex, shown in the high magnification insets. Yellow lines represent the segments applied to measure cortical thickness (see Materials and Methods for details on the quantification). Scale bar (main figure) = 1mm; scale bar (insets) = 25μm. H. Histograms showing the quantification of cortical thickness. SM = somatomotor; SS = somatosensory; V = visual cortex. ** = p < 0.01; Kruskal Wallis followed by Dunn's post-hoc test (for SM) or ANOVA followed by Tukey's post-hoc test (for SS and V). D",
    "ncbi_link": "Ppt1: 19063"
  },
  {
    "caption": "C. Significant increase of the survival in Ppt1-/- mice receiving the administration of hPPT1-LV transduced HSPCs.",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "E, F. Significant prevention of pathological symptoms (DSS higher than 4 and limbs stiffness) in Ppt1-/- mice transplanted with hPPT1-LV transduced HSPCs.",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "E. Representative fluorescence microscope photomicrographs showing autofluorescent storage material (AF, green) in different brain regions of Ppt1-/- mice transplanted with hPPT1-LV transduced HSPCs at 400-420 days of age, when the study was terminated. Mock transplanted and untreated Ppt1 -/- mice at about 250 days, i.e. humane end point, are shown as reference; 450 days-old untreated wild type Ppt1+/+ are shown as control. Neurotrace fluorescent Nissl staining (NT, red) is used to highlight neurons in different brain regions. Arrows highlight the surviving Purkinje cells in the cerebellum of IV and ICV+IV transplanted mice; arrowheads highlight the high number of AF+ cells in the Purkinje cell layer of ICV transplanted or Ppt1-/- untreated (UT) mice. Scale bar = 100μm.",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "A. Quantification of cortical thickness in the somatosensory (SS), somatomotor (SM) and visual (V) area, in untreated Ppt1-/- or Ppt1+/+ mice and in mice transplanted (tx) with hPPT1-LV transduced HSPCs IV, ICV or ICV+IV or mock-transplanted, analyzed at study termination. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001; Kruskal Wallis followed by Dunn's post-hoc test.",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "B. Quantification of CD68 immunoreactivity in the cortex, hippocampus, thalamus and cerebellum of untreated (UT) or gene therapy treated Ppt1-/- mice. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.00001; Kruskal Wallis followed by Dunn's post-hoc test.",
    "ncbi_link": "Ppt1: 19063"
  },
  {
    "caption": "A. Significant increase of the survival in Ppt1-/- mice transplanted at the symptomatic stage with hPPT1-LV transduced HSPCs administered IV+ICV.",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "E. Representative fluorescence microscope photomicrographs showing autofluorescent storage material (AF, green) in different brain regions of Ppt1-/- mice transplanted with hPPT1-LV transduced HSPCs at 18-20 weeks of age, analyzed at study termination. Ppt1 -/- mice mock transplanted at 18-20 weeks of age and analyzed at about 250 days, i.e. humane end point, are shown as reference. Neurotrace fluorescent Nissl staining (NT, red) is used to highlight neurons in different brain regions. Scale bar = 100 μm. F. Top panel: quantification of autofluorescent (AF) storage material in different brain regions of untreated or transplanted mice analyzed at study termination. ** = p<0.01; *** = p< 0.001; **** = p< 0.0001; 2-way ANOVA followed by Tukey's post-hoc test. Bottom panel: histograms showing the quantification of cortical thickness. SM = somatomotor; SS = somatosensory; V = visual cortex. * = p <0.05; ** = p<0.01; **** = p<0.0001; Kruskal Wallis followed by Dunn's post-hoc test (for SM and V area) or ANOVA followed by Tukey's post-hoc test (for SS area). S",
    "ncbi_link": "Ppt1: 19063
PPT1: 5538"
  },
  {
    "caption": "IFM images of KIF13A-YFP transfected control and Rab-knockdown HeLa cells. TN: average tubule number (mean±SEM, n=3). B, C Graphs represent the measurement of KIF13A-positive TN (B) and TL (C) in HeLa cells of Fig 1A (mean± SEM). n=3. nc: total number of cells. nt: total number of tubules.arrowheads and arrows point to the KIF13A-/Rab22A-positive tubular REs and E/SEs respectively. Scale bars: 10 μm.",
    "ncbi_link": "Rab: 
KIF13A: 63971"
  },
  {
    "caption": "IFM images of KIF13A-YFP and mCherry-Rab7A/11A/22A transfected HeLa cells arrowheads and arrows point to the KIF13A-/Rab22A-positive tubular REs and E/SEs respectively. Scale bars: 10 μm",
    "ncbi_link": "mCherry: 
YFP: 
KIF13A: 63971
11A: 8766
22A: 19334
Rab7A: 7879"
  },
  {
    "caption": "Live cell imaging of GFP/mCherry-Rab22A with respect to mCherry-Rab11A or GFP-Rab7A in HeLa cells. Magnified view of insets (at 0, 20, 40 seconds) are shown separately ), arrowheads and arrows point to the KIF13A-/Rab22A-positive tubular REs and E/SEs respectively. Scale bars: 10 μm",
    "ncbi_link": "GFP: 
mCherry: 
Rab11A: 8766
Rab22A: 19334
Rab7A: 7879"
  },
  {
    "caption": "IFM images of KIF13A-YFP and mCherry-Rab22AWT/Q64L/S19N cotransfected HeLa cells. Arrowheads and arrows point to the KIF13A-positive tubular REs and E/SEs respectively. The colocalization coefficient (r, in mean±SEM) between two markers was indicated separately. Scale bars: 10 μm Graphs represent the measurement of KIF13A-positive TN (B) and TL (C) in HeLa cells of Fig 2A. n=3. nc: total number of cells. nt: total number of tubules",
    "ncbi_link": "mCherry: 
YFP: 
KIF13A: 63971
Rab22A: 19334"
  },
  {
    "caption": "IFM images of KIF13A-YFP transfected control and Rab22A-, BLOC-1Mu-, BLOC-2HPS6- knockdown HeLa cells. Cells were stained for AP-1 (γ) or internalized with Tf-Alexa fluor 594 arrowheads and arrows point to the KIF13A-/Rab22A-positive tubular REs and E/SEs respectively. Scale bars: 10 μm",
    "ncbi_link": "YFP: 
BLOC-1Mu: 63915
BLOC-2HPS6: 79803
KIF13A: 63971
Rab22A: 57403"
  },
  {
    "caption": "Immunoblotting analysis of proteins in control and Rab22A-, BLOC-1-, BLOC-2-depleted HeLa cells. *, non-specific bands. Protein band intensities were quantified and indicated on the gels.",
    "ncbi_link": "BLOC-2: 79803
BLOC-1: 63915
Rab22A: 57403"
  },
  {
    "caption": "IFM images of mCherry-Rab22A and KIF13A-YFP cotransfected control and BLOC-1Mu-, BLOC-2HPS6- knockdown HeLa cells ), arrowheads and arrows point to the KIF13A-/Rab22A-positive tubular REs and E/SEs respectively. Scale bars: 10 μm",
    "ncbi_link": "mCherry: 
YFP: 
BLOC-1Mu: 63915
BLOC-2HPS6: 79803
KIF13A: 63971
Rab22A: 19334"
  },
  {
    "caption": "BF and IFM images of control and Rab22A-depleted melanocytes. The colocalization coefficient (r, in mean±SEM) between the two markers indicated separately. Nuclei are stained with Hoechst33258 ), arrows indicate the melanocyte pigmentation and arrowheads point to the localization of TYRP1/GFP-Rab22A. Scale bars: 10 μm",
    "ncbi_link": "Rab22A: 19334"
  },
  {
    "caption": "Graph represents the quantified melanin content in control sh, Rab22A sh and BLOC-1- melanocytes. n=3. The fold-change in melanin content (mean±SEM) indicated separately",
    "ncbi_link": "BLOC-1: 17828
Rab22A: 19334"
  },
  {
    "caption": "Immunoblotting analysis of proteins in Control sh and Rab22A sh melanocytes ), protein band intensities were quantified and indicated on the gels",
    "ncbi_link": "Rab22A: 19334"
  },
  {
    "caption": "EM of control and Rab22A-knockdown MNT-1 melanocytes. Arrowheads indicate PMEL fibrils. Scale bars: 1 μm. I, II, III, IV: stages of melanosomes. M: mitochondria. Magnified view of insets are shown separately and they emphasize the stage I melanosomes in both conditions. Note: the presence of hybrid stage I/II melanosomes in Rab22A-knockdown cells. Insets (b)-(d) and (g)-(h) are from different cells of respective condition. Scale bars: 200 nm.",
    "ncbi_link": "Rab22A: 57403"
  },
  {
    "caption": "BF and IFM images of GFP-Rab22A transfected BLOC-1-(Mu) melanocytes ), arrows indicate the melanocyte pigmentation and arrowheads point to the localization of TYRP1/GFP-Rab22A. Scale bars: 10 μm",
    "ncbi_link": "GFP: 
BLOC-1-(Mu): 17828
Rab22A: 19334"
  },
  {
    "caption": "Immunoblotting analysis of proteins in BLOC-1- and BLOC-1R melanocytes protein band intensities were quantified and indicated on the gels",
    "ncbi_link": "BLOC-1: 17828"
  },
  {
    "caption": "Subcellular membrane fractionation of control and Rab22A-, BLOC-1-, BLOC-2-knockdown HeLa cells and probed the fractions for pallidin, dysbindin and muted. Red colored box emphasizes BLOC-1 membrane association in the respective cell types.",
    "ncbi_link": "BLOC-2: 79803
BLOC-1: 63915
Rab22A: 57403"
  },
  {
    "caption": "Pull-down of His-Rab22AWT using HeL lysate the bead bound His-Rab22A/His-KIF13A domains were shown as coomassie stained gel separatel",
    "ncbi_link": "Rab22A: 19334"
  },
  {
    "caption": "Pull-down of His-Rab22AWT usin melanocyte (E) lysate. In E, the beads were preloaded with GTPγS or GDP the bead bound His-Rab22A/His-KIF13A domains were shown as coomassie stained gel separatel",
    "ncbi_link": "Rab22A: 19334"
  },
  {
    "caption": "Pull-down of different His-KIF13A domains using HeLa cell lysate the bead bound His-Rab22A/His-KIF13A domains were shown as coomassie stained gel separatel",
    "ncbi_link": "KIF13A: 63971"
  },
  {
    "caption": "(A) Abnormal distribution of Cux1-positive neurons in CAMDI-KO mice. Expression of Cux1 in the somatosensory cortex was compared between P2 wild-type (WT) and CAMDI-KO (KO) mice. Scale bar, 100 μm.(B) Quantification of the number of Cux1-positive neurons. Note the abnormal distribution of neurons in deep cortical layers of CAMDI-KO mice. n = 3 mice/genotype (WT = 788 cells, KO = 2,139 cells). *, p<0.05, **, p<0.01, ***, p<0.001, Two-way ANOVA followed by Scheffe's post-hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(C) Delay in neuronal migration by CAMDI deletion. Coronal sections through the somatosensory cortex of P21 WT and CAMDI-KO mice were analyzed following in utero electroporation of EGFP plasmid at E14.5. Scale bar, 100 μm.(D) Quantification of the number of EGFP-positive neurons. Note the abnormal distribution of neurons in lower cortical layers of CAMDI-KO mice. n = 3 for WT mice (546 cells), n = 4 for KO mice (680 cells). *, p<0.05, ***, p<0.001. Two-way ANOVA followed by Scheffe's post-hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(E) Aberrant axonal projection and terminal arbors by CAMDI deletion. Coronal sections through the somatosensory cortex of P21 WT and CAMDI-KO mice were analyzed following in utero electroporation of EGFP plasmid at E14.5. Representative pictures show an aberrant axonal projection of corticostriatal neurons in CAMDI-KO mice. Sections were stained with Hoechst 33258 and anti-EGFP antibody. Scale bar, 1 mm.(F) Quantification of the striatal intensity. n = 3 mice/genotype. ***, p<0.001, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(A, B) Representative traces from adult control (WT) and CAMDI-KO (KO) in open field test. Locomotor activity (A) and distance traveled (B) for 15 min. n = 8 for WT mice, n = 7 for KO mice. *, p<0.05, One-way ANOVA with Bonferroni's post hoc test (F(1, 13) = 5.53). Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(C, D) N-terminal region of CAMDI recognizes the second HDAC domain of HDAC6. SH-SY5Y cells were co-transfected with HDAC6-HA and each FLAG-CAMDI fragment (C) (fragment 1, 1-250; 2, 251-500; 3, 501-750; 4, 751-1000; 5, 1001-1451 amino acids) or co-transfected with FLAG-CAMDI and each HDAC6-HA fragment (D) (fragment 1 (DD1), 1-440; 2 (DD2), 441-840; 3, 841-1215 amino acids). Co-IP assay was performed with the indicated antibodies. n=3 independent experiments. **, p<0.01, ***, p<0.001, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134
HDAC6: 15185"
  },
  {
    "caption": "(A) CAMDI and CAMDI Fragment 1 overexpression enhanced α-tubulin acetylation. HeLa cells overexpressing FLAG-CAMDI and FLAG-CAMDI frag.1 were immunostained with anti-FLAG or anti-Ac-tubulin antibodies. Ratio line-scans along the line (from x- to y-axis) from images. Scale bar, 10 μm.",
    "ncbi_link": "CAMDI: 311134"
  },
  {
    "caption": "(B-C) CAMDI blocked HDAC6-mediated α-tubulin deacetylation. (C) CAMDI N-terminal domain alone increased Ac-tubulin level. n=3 independent experiments. **, p<0.01, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134"
  },
  {
    "caption": "(D) Deletion of CAMDI N-terminal domain (1-250 amino acids) failed to inhibit HDAC6. n = 3 independent experiments. N.S., not significant. Two-way ANOVA followed by Scheffe's post-hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134
HDAC6: 15185"
  },
  {
    "caption": "(A) Effect of HDAC6 over-expression or CAMDI co-expression on the level of acetylated α-tubulin in the centrosome. HeLa cells co-transfected with Centrin2-EGFP with/without HDAC6-HA and FLAG-CAMDI were immunostained with anti-EGFP (green) and anti-acetylated α-tubulin antibodies (red). Scale bar, 1 μm.(B) Quantification of intensity of acetylated α-tubulin at centrosome. n = 25, 30, 30 cells. *, p<0.05, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134
HDAC6: 15185"
  },
  {
    "caption": "(C) Effects of HDAC6 overexpression or CAMDI co-expression on the centrosomal localization of γ-tubulin. HeLa cells co-transfected with Centrin2-EGFP with/without HDAC6-HA and FLAG-CAMDI were immunostained with anti-EGFP (green) and anti-γ-tubulin antibodies (red). DNA was stained with Hoechst 33258. Scale bar, 1 μm.(D) Quantification of intensity of γ-tubulin at centrosome. n = 39, 16, 17 cells. *, p<0.05, **, p<0.01, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134
HDAC6: 15185"
  },
  {
    "caption": "(E) CAMDI stabilizes centrosomal γ-tubulin through HDAC6 inhibition. Centrosomal fraction was isolated from cell lysates of SH-SY5Y cells expressing each construct, and γ-tubulin level was assessed by immunoblot analysis. n = 3 independent experiments. **, p<0.01, One-way ANOVA followed with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 311134
HDAC6: 15185"
  },
  {
    "caption": "(F) Effects of CAMDI knockdown on the centrosomal localization of γ-tubulin in vivo.Coronal sections through the somatosensory cortex of E17.5 were analyzed following in utero electroporation of EGFP and CAMDI-sh plasmid at E14.5. The sections were immunostained with anti-EGFP (green) and anti-γ-tubulin antibodies (red). Representative images of EGFP at Cortical Plateneuron expressing CAMDI-sh stained for endogenous γ-tubulin and with Hoechst (blue). Z-stack number 6 indicates centrosome of EGFP-positive CAMDI-sh-expressing neuron. Z-stack number 19 indicates centrosome of a nearby non-electroporated neuron. Quantification of γ-tubulin intensity. EGFP (-) = 12 cells, EGFP (+) (CAMDI-sh) = 12 cells. *, p<0.05, One-way ANOVA with Bonferroni's post hoc test. Data are presented as mean ± SEM. Scale bar, 5 μm.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(G) Reduced γ-tubulin in the centrosome fraction of CAMDI-KO brain. The centrosomal fraction was isolated from brain lysates of WT and CAMDI-KO mice and γ-tubulin level was assessed by immunoblot analysis. n = 3 independent experiments. **, p<0.01, One-way ANOVA followed with Bonferroni's post hoc test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(A) Rescue of a delayed cortical migration in CAMDI-KO mice by Tubastatin A. Immunohistochemical analysis of Cux1 expression in the somatosensory cortex at P2 after intraperitoneal injections of Tubastatin A into pregnant CAMDI-KO mice from E12.5-17.5. Scale bar, 100 μm.(B) Quantification of the number of Cux1-positive neurons. Note the abnormal distribution of neurons in deep cortical layers of CAMDI-KO mice. n = 3 mice/genotype (WT (vehicle) = 3,628 cells, KO (vehicle) = 2,816 cells, WT (Tubastatin A) = 1,847 cells, KO (Tubastatin A) = 2,364 cells). *, p<0.05, **, p<0.01, Two-way ANOVA followed by Tukey HSD test. Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "(A) Representative traces from control (WT) and CAMDI-KO (KO) mice in the open field test at P21. Sample traces of locomotor activity were shown.(B) Distance traveled for 10 min. n = 13 for WT (vehicle) mice, n = 13 for KO (vehicle) mice, n = 5 for WT (Tubastatin A) mice, n = 16 for KO (Tubastatin A) mice. **, p<0.01, ***, p<0.001. Two-way ANOVA followed by Scheffe's post-hoc test (main effect of genotype F(1, 43)=6.25, main effect of drug F(1, 43)=2.14, interaction F(1, 43)=12.68). Data are presented as mean ± SEM.",
    "ncbi_link": "CAMDI: 545428"
  },
  {
    "caption": "Immunoprecipitation  of SATB2  from mouse neonatal cortical  lysates. LEMD2  was detected by Western blotting in the SATB2-immunoprecipitate  from control but not SATB2-deficient cortical  lysate. The equal input of total protein from control and SATB2-deficient cortical  lysates was controlled by ERK2  detection. Representative images of the immunoblots  are shown; I (Input), F (Flow-through), B (Beads).",
    "ncbi_link": "SATB2: 212712"
  },
  {
    "caption": "Immunoprecipitations  using anti-V5-tag antibody from lysates of HeLa cells transfected with expression plasmids encoding V5-tagged full-length SATB2  (Satb21-733) and EGFP  as control. The equal input of total protein was controlled by GAPDH  detection. Representative images of the immunoblots  are shown; I (Input), F (Flow‐through), B (Beads), M (Molecular weight marker).",
    "ncbi_link": "EGFP: 
SATB2: 
Satb2: 
V5: "
  },
  {
    "caption": "The CUT-like domain of SATB2  is required for the interaction  with LEMD2. Immunoprecipitations  using anti-V5-tag antibody from lysates of HeLa  cells transfected with  V5-tagged Satb21-247 and Satb21-157 deletion mutants. LEMD2  and BAF  were detected only in immunoprecipitates  from HeLa  cells transfected with the deletion mutant containing the CUT-like domain (Satb21-247). The equal input of total protein was controlled by GAPDH  detection. Representative images of the immunoblots  are shown; I (Input), F (Flow‐through), B (Beads), M (Molecular weight marker).",
    "ncbi_link": "Satb2: 
V5: "
  },
  {
    "caption": "CUT1 and CUT2 domains are required for the interaction  with LEMD2. Immunoprecipitations  using anti-V5-tag antibody from HeLa  cells transfected with  V5-tagged Satb2346-733 and  Satb2616-733 deletion mutants. LEMD2  and BAF  were detected only in immunoprecipitates  from HeLa  cells expressing the CUT1 and CUT2 containing deletion mutant (Satb2346-733).",
    "ncbi_link": "Satb2: 
V5: "
  },
  {
    "caption": "Activity-induced formation of nuclear  infoldings is abolished in SATB2-defficient hippocampal neurons. Bic-induced AP bursting for 1 h caused a significant increase in the percentage of infolded nuclei  in DIV10 hippocampal  cultures derived from Satb2flx/flx mice  but not from  Satb2flx/flx::Nes-Cre mice  (Satb2NesCre) (n = 6 independent primary cultures, two-way ANOVA, F1,20 = 9.51, significant interaction p = 0.0058, simple main effects analysis, Satb2flx/flx cultures, Bic-treated vs untreated p = 0.0000043, Satb2NesCre cultures, Bic-treated vs untreated p > 0.05, adjustment for multiple comparisons: Bonferroni, number of analyzed nuclei: Satb2flx/flx cultures, untreated - 680, Satb2flx/flx cultures, Bic-treated - 711, Satb2NesCre, untreated - 755, Satb2NesCre, Bic-treated - 720). Data are presented as mean ± SEM, ***p < 0.001.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
SATB2: 212712
Satb2: 212712"
  },
  {
    "caption": "Activity-induced formation of nuclear  infoldings is impaired in  SATB2-deficient  cortical neurons. DIV14 cortical  cultures form Satb2flx/flx and Satb2NesCre mice  were silenced with NBQX  for 1 h followed by stimulation with Bic  for 1 h. The percentage of infolded nuclei  following AP bursting was increased in control Satb2flx/flx cultures but not in SATB2-deficient cultures (n = 3-4 independent primary cultures, two-way ANOVA, F1,10 = 39.124, significant interaction p = 0.000094, simple main effects analysis, Satb2flx/flx cultures: Bic-treated vs NBQX-treated p = 7.66E-07, Satb2NesCre cultures: Bic-treated vs NBQX-treated p > 0.05, adjustment for multiple comparisons: Bonferroni, number of analyzed nuclei: Satb2flx/flx cultures, NBQX  - 606, Satb2flx/flx cultures, Bic  - 910; Satb2NesCre cultures, NBQX -604, Satb2NesCre cultures, Bic  - 835). Data are presented as mean ± SEM, ***p < 0.001.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
SATB2: 212712
Satb2: 212712"
  },
  {
    "caption": "Confocal  images (z-axis-projected stacks) of Lamin B2 stained neuronal nuclei from the CA1 pyramidal cell layer of adult Satb2flx/flx and Satb2flx/flx::CamK2a-Cre (Satb2CamkCre) mice. Scale bars: 10 μm.",
    "ncbi_link": "Camk: 12322
CamK2a: 12322
Cre: 2777477
Satb2: 212712"
  },
  {
    "caption": "Analysis of the percentage of infolded nuclei in the hippocampus  of  Satb2flx/flx mice vs Satb2CamkCre mice. In Satb2flx/flx mice, the number of infolded nuclei  was significantly higher in the CA1 area compared to the CA3  area (p = 0.000001) and DG  (p = 1.8 E-12). In Satb2CamkCre mice, the number of infolded nuclei in the CA1 area was significantly reduced compared to the corresponding number in littermate controls (p = 1.9 E-09). No significant differences were observed in this number in the CA3 and DG between Satb2CamkCre mice and floxed controls (n = 4 mice, two-way ANOVA, significant interaction, F2,18 = 47.81, p = 0.00001, simple main effects analysis, CA1 area, Satb2flx/flx vs CKO mice p = 1.9 E-09, CA3  area, Satb2flx/flx vs CKO mice  p = 0.909,  DG, Satb2flx/flx vs CKO mice  p = 0.262, adjustment for multiple comparisons: Bonferroni). Number of analyzed nuclei: Satb2flx/flx mice: 469 (CA1), 225 (CA3), 665 (DG); Satb2CamkCre: 508 (CA1), 224 (CA3), 575 (DG). Data are presented as mean ± SEM, ***p < 0.001.",
    "ncbi_link": "Camk: 12322
Cre: 2777477
Satb2: 212712"
  },
  {
    "caption": "Analysis of the percentage of infolded nuclei  in the CA1 pyramidal cell layer of  Satb2CamkCre mice  vs. littermate controls after stereotaxic injections of AAV-SATB2-V5  or AAV8-EGFP. Viral delivery of  SATB2  resulted in restoration of the number of infolded nuclei  in the CA1 pyramidal cell  layer of Satb2CamkCre mice  (n = 3-5 mice, one-way ANOVA followed by Hochberg post hoc test, F2,9 = 33.1, Satb2CamkCre::AAV-SATB2 vs. Satb2flx/flx::AAV-EGFP, p = 0.0012; Satb2flx/flx::AAV-EGFP vs. Satb2CamkCre::AAV-EGFP, p = 0.00008, Satb2flx/flx::AAV-EGFP vs. Satb2CamkCre::AAV-SATB2, p = 0.072). Number of analyzed  nuclei: 388 (Satb2flx/flx::AAV-EGFP), 560 (Satb2CamkCre::AAV-EGFP), 546 (Satb2CamkCre::AAV-SATB2). Data are presented as mean ± SEM, ***p < 0.001 compared to  Satb2flx/flx::AAV-EGFP, ##p < 0.01, compared to Satb2CamkCre::AAV-EGFP.",
    "ncbi_link": "V5: 
EGFP: 
Camk: 12322
Cre: 2777477
Satb2: 212712
SATB2: 212712"
  },
  {
    "caption": "Nuclear  infolding triggered by SATB2  overexpression requires LEMD2. Analysis of the percentage of infolded nuclei  in DIV10 hippocampal neurons  upon Satb2  overexpression and Lemd2  knockdown. AAV-SATB2-transduced neurons (both non-transfected and scrambled siRNA-transfected, Scr) exhibited higher percentage of infolded nuclei  compared to AAV-EGFP-transduced neurons. In contrast, LEMD2-depleted AAV-SATB2-transduced cultures showed similar percentage of infolded nuclei  to  AAV-EGFP-transduced neurons (n = 3-4 independent primary cultures; one-way ANOVA F3,11 = 30.982, p = 0.000011; Hochberg post hoc test, AAV-EGFP vs. AAV-SATB2 p = 0.0001, AAV-EGFP vs. AAV-SATB2 + Scr p = 0.0001,  AAV-EGFP vs.  AAV-SATB2 + siLemd2 p= 0.9999, AAV-SATB2 + Scr vs. AAV-SATB2  + siLemd2 p = 0.0001). Number of nuclei  analyzed: 460 (AAV-EGFP), 466 (AAV-SATB2), 537 (AAV-SATB2 + Scr), 597 (AAV-SATB2+siLem2). Data are presented as mean ± SEM, ***p < 0.001 compared to AAV-EGFP; ###p < 0.001 compared to AAV-SATB2 + Scr.",
    "ncbi_link": "EGFP: 
Lemd2: 224640
Lem2: 224640
LEMD2: 224640
Satb2: 212712
SATB2: 212712"
  },
  {
    "caption": "Activity-induced formation of nuclear  infoldings is impaired in LEMD2-depleted cortical neurons. Bic-triggered AP bursting for 1 h caused a significant increase in the percentage of infolded nuclei  in  cortical neurons transduced with AAV-scrambled but not with AAV-shLemd2  virus (n = 5 independent primary cultures, two-way ANOVA, F1,16 = 8.35, significant interaction p = 0.0107, simple main effects analysis: AAV-scrambled-transduced cultures, Bic-treated vs untreated p = 0.0049, AAV-shLemd2-transduced cultures, Bic-treated vs untreated p > 0.99, adjustment for multiple comparisons: Bonferroni). Data are presented as mean ± SEM, **p < 0.01 compared to NBQX-treated cultures.",
    "ncbi_link": "Lemd2: 224640
LEMD2: 224640"
  },
  {
    "caption": "LEMD2  is required for the nuclear envelope infoldings of CA1 pyramidal neurons in vivo. Top panel: representative confocal  images (z-axis-projected stack) of Lamin B2/DAPI-stained coronal brain   sections from wild-type mice after stereotaxic injection of AAV-shRNA viruses (AAV-shLemd2-mCherry or  AAV-scrambled-mCherry) into the dorsal hippocampus. Merged,  colocalization of the three signals. Scale bars: 50 μm. Middle panel: higher magnification images of AAV-shLemd2-transduced CA1 pyramidal neurons. Arrows show examples of mCherry-positive nuclei that are devoid of nuclear infoldings, whereas stars denote non-transduced infolded nuclei. Lower panel: higher magnification images of AAV-scrambled siRNA-transduced  CA1 pyramidal neurons. Arrows show examples of infolded, mCherry-positive nuclei; stars denote infolded, non-transduced neurons. Scale bars (middle and lower panels): 10 μm.",
    "ncbi_link": "mCherry: 
LEMD2: 224640
Lemd2: 224640"
  },
  {
    "caption": "Analysis of the percentage of infolded nuclei  in DIV10 hippocampal neurons upon SATB2 overexpression and  Vps4a/ Vps4b knockdown. AAV-SATB2-transduced neurons (non-transfected or scrambled siRNA (Scr)-transfected) exhibited higher percentage of infolded nuclei  compared to AAV-EGFP-transduced neurons. In contrast, VPS4-depleted  AAV-SATB2-transduced cultures showed similar number of infolded nuclei to AAV-EGFP-transduced neurons (n = 4 independent primary cultures, one-way ANOVA followed by Tuckey post hoc test, F3,11 =15.866, p = 0.00026, AAV-EGFP vs. AAV-SATB2 p = 0.0104, AAV-EGFP vs. AAV-SATB2 + Scr p = 0.0028, AAV-EGFP vs. AAV-SATB2 + siVps4 p = 0.605, AAV-SATB2 + Scr vs. AAV-SATB2 + siVps4 p = 0.0007). Number of  nuclei  analyzed: 594 (AAV-EGFP), 657 (AAV-SATB2), 612 (AAV-SATB2 + Scr), 428 (AAV-SATB2 + siVps4). Data are presented as mean ± SEM, **p < 0.01 compared with AAV-EGFP; ###p < 0.001 compared with AAV-SATB2 + Scr.",
    "ncbi_link": "EGFP: 
SATB2: 212712
Vps4a: 116733
Vps4: 116733///20479
Vps4b: 20479
VPS4: 20479///116733
Vps4: 20479///116733"
  },
  {
    "caption": "Activity-induced formation of nuclear  infoldings is impaired in VPS4-depleted cortical neurons. Upon AP bursting, the percentage of infolded nuclei was increased in non-transfected cultures and in cultures transfected with scramble siRNA (Scr) but not with siVps4 (n = 3-4 independent primary cultures, one-way ANOVA followed by Tuckey post hoc test, F3,8 = 90.525, p = 1.63E-06,  Bic-treated vs NBQX-treated p = 0.000012, Scr Bic-treated vs NBQX-treated p = 0.000052, siVps4 Bic-treated vs NBQX-treated p = 0.396, siVps4 Bic-treated vs Scr Bic-treated p = 0.000015). Number of analyzed  nuclei: 474 (NBQX), 456 (Bic), 409 (Bic + Scr), 383 (Bic + siVps4). Data are presented as mean ± SEM, ***p < 0.001 compared to NBQX-treated, ###p < 0.001 compared to Scr Bic-treated.",
    "ncbi_link": "VPS4: 116733///20479
Vps4: 116733///20479
Vps4: 20479///116733"
  },
  {
    "caption": "Representative confocal  images (Z-axis projection) of CA1 pyramidal neurons of: (top panel) Satb2 floxed mice  (n = 3) maintained in their home cages (HC), (middle panel) Satb2 floxed mice  (n = 4) subjected to NEE  for 1.5 h, (bottom panel) Satb2CamkCre mice  (n = 5) exposed to NE for 1.5 h. Brain  sections were stained for cFos and Lamin B2. Scale bars: 10 μm. Higher magnification views of boxed areas in A (middle panel). Arrows show examples of infolded, cFos-positive nuclei  of the CA1 field of Satb2 floxed mice  subjected to  NEE. Scale bars: 5 μm.",
    "ncbi_link": "Camk: 12322
Cre: 2777477
Satb2: 212712"
  },
  {
    "caption": "(f,g) Northern blot analyses of TbMCU RNAi of BSF (f) and PCF (g) trypanosomes grown in the absence (0) and presence (2-8; 2-10) of tetracycline (top). Tubulin is shown as a loading control (bottom). Markers are shown on the right. The transcript of TbMCU, including the 5′- and 3′-UTR was ~1.5 kb in length.",
    "ncbi_link": "TbMCU: 
Tubulin: "
  },
  {
    "caption": "(h,i) Western blot analyses of TbMCU RNAi of BSF (h) and PCF (i) trypanosomes grown in the absence (0) or presence (2-8; 2-10) of tetracycline. Total lysates (30 μg) were subjected to 10% SDS-polyacrylamide gel electrophoresis before transfer to a nitrocellulose membrane and then stained with antibodies against TbMCU (top). One band of ~30 kDa was detected in T. brucei homogenates. Membranes were stripped and re-incubated with antibody against the voltage-dependent anion channel (TbVDAC) as a loading control (bottom).",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(e) Representative traces of Ca2+ uptake kinetics in digitonin-permeabilized TbMCU BSF trypanosomes cultured in the absence (−Tet) or presence (+Tet) of tetracycline. The reactions were started adding 40 μM digitonin in the presence of 1 mM ATP and 500 μM sodium orthovanadate. Ca2+ uptake was monitored over time using 1 μM Calcium Green-5N. Ruthenium red (RR, 40 μM, yellow and red tracings), oligomycin (Oligo, 2.5 μg ml−1), EGTA (0.4 μM) and CaCl2 (pulses of 0.4 μM) were added where indicated. (f) Relative Ca2+ uptake at 200 s as compared with that of control BSF trypanosomes grown in the absence of tetracycline considered as 1 (−Tet) (means±s.d., n=3, *(+Tet±RR), **(−Tet±RR), ***(−Tet/+Tet) , P0.001, Student's t-test).",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(g) Groups of five mice were infected with WT T. brucei (black line) or trypanosomes transfected with the construct for RNAi of TbMCU (red line). Doxycycline (green line; 200 μg ml−1) was given in the drinking water throughout a 30-day period.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(a) Growth of TbMCU-KO BSF in the absence (black line) or presence (red line) of 1 μg ml−1 tetracycline for the indicated number of days. Addition of 10 mM threonine to the medium (green line) partially rescued the mutant BSF trypanosomes but had no effect on +Tet cells (yellow line; means±s.d., n=3, **P0.001, Student's t-test).",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(c) Northern blot analysis of wild-type (WT) and TbMCU-KO BSF cultured in the presence (+Tet) or absence (−Tet) of tetracycline for 2 days. Tubulin is shown as a loading control (bottom panel).",
    "ncbi_link": "TbMCU: 
Tubulin: "
  },
  {
    "caption": "(e) Immunofluorescence analysis of control (upper panels) and TbMCU-KO (lower panels) trypanosomes. TbMCU co-localized with MitoTracker (MT) in the control parasites (+Tet; PCC=0.808). Scale bar, 10 μm.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(f) Conditional TbMCU-KO BSF trypanosomes were grown in the presence (+Tet) or absence (−Tet) of tetracycline for 2 days. BSF trypanosomes (2 × 108 cells) were incubated as in Fig. 2e. Multiple pulses of CaCl2 (arrowheads) were added to a final concentration of 20 μM. A representative trace (red or black) of Ca2+ uptake from one of three independent experiments is shown.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(a) Rhod-2 fluorescence in control or overexpressing TbMCU (TbMCU-OE) PCF. Scale bar, 10 μm. (b,c) Rhod-2 (mitochondrial) (b) and Fluo-4 (cytosolic) (c) fluorescence in control (−Tet) and overexpressing TbMCU (+Tet) PCF (means±s.d., n=3, **P0.05, Student's t-test); NS, not significant.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(d) Ca2+ uptake by digitonin-permeabilized PCF overexpressing TbMCU. Trypanosomes were incubated as in Fig. 2c. Multiple pulses of CaCl2 (arrowheads) were added to a final concentration of 8 μM. (e) Ca2+ uptake in TbMCU-OE PCF (+Tet) 200 s after addition of Ca2+, as compared with uninduced trypanosomes considered as 1 (−Tet) (means±s.d., n=3, **P0.01, Student's t-test).",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(f) Mitochondrial membrane potential of digitonin-permeabilized control (−Tet) and TbMCU-OE (+Tet) PCF. The reactions were incubated as in Fig. 3a.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(h) Mitochondrial oxidative stress as measured with MitoSOX Red in control (C) and TbMCU-overexpressing (OE) PCF permeabilized with 50 μM digitonin in the presence of 0.4 mM Ca2+. Controls were treated with 2 μM antimycin A (C+AA), or were trypanosomes exposed to 0.4 mM Ca2+ in the absence of digitonin (−DIG+Ca2+), and trypanosomes permeabilized with digitonin in the absence of Ca2+ (C, yellow line). (i) Quantification of change at 900 s. Results are expressed as mean fluorescence±s.d. (n=3, **P0.001, Student's t-test).",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(j) Growth of trypanosomes in the absence (control, black lines) or presence (TbMCU-OE, red lines) of 1 μg ml−1 tetracycline (means±s.d., n=3). (k) Dead cells in representative fields of control (−Tet) and TbMCU-OE (+Tet) PCF are indicated (white arrows). Scale bar, 10 μm.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "(l) Cell viability on apoptotic challenge of control (−Tet) or TbMCU-OE (+Tet) PCF trypanosomes with H2O2 and C2-ceramide. The percentage of cell death was obtained from means±s.d. by analysing >60 fields (including >400 cells) (n=3). **P0.01, Student's t-test.",
    "ncbi_link": "TbMCU: "
  },
  {
    "caption": "A-D LSM images of proximity ligation assay (PLA) dots composed of VEGFR3 and phosphorylated tyrosine (p-Tyr) on cross-sections through the jugular lymph sac / primordial thoracic duct (jls/pTD) of E13.5 control and ILK K.O. embryos. Scale bars: 10 µm. E-H LSM images of PLA dots composed of VEGFR2 and phosphorylated tyrosine (p-Tyr) on cross-sections through the jls/pTD of E13.5 control and ILK K.O. embryos. Scale bars: 10 µm. I Quantification of the PLA dots indicating VEGFR3 with phosphorylated tyrosine (p-Tyr) per LEC of E13.5 control or ILK K.O. embryos (n = 9 embryos per genotype), *P = 0.022. J Quantification of the PLA dots indicating VEGFR2 with phosphorylated tyrosine (p-Tyr) per LEC of E13.5 control or ILK K.O. embryos (n = 3 embryos per genotype). K Quantification of the total number of PLA dots indicating both VEGFR2 (left) and VEGFR3 (right) with phosphorylated tyrosine (p-Tyr) per jls/pTD section of E13.5 control or ILK K.O. embryos (n = 3 embryos per genotype), *P = 0.005 (VEGFR2/p-Tyr in ILK K.O. versus VEGFR3/p-Tyr in ILK K.O.), *P = 0.013 (VEGFR3/p-Tyr in control versus VEGFR3/p-Tyr in ILK K.O.)",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "LSM images of proximity ligation assay (PLA) dots (arrows) composed of VEGFR3 and β1 integrin on cross-sections through the jls/pTD of E13.5 control and ILK K.O. embryos. Scale bars: 10 µm Quantification of VEGFR3/β1 integrin PLA dots normalised to Lyve1-positive area of control or ILK K.O. embryos (n = 6 embryos per genotype),",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "Bright-field image of an E13.5 Flk1-Cre;Ilk∆/+;Itgb1∆/+ mouse embryo (referred to as "Control") with a heterozygous deletion of both Ilk and Itgb1 in endothelial cells, and a LSM image of a stained cross-section through its jugular lymph sac / primordial thoracic duct (jls/pTD). Scale bars: 500 and 100 µm, respectively. C, D Bright-field image of an E13.5 Flk1-Cre;Ilk∆/∆;Itgb1∆/+ embryo (referred to as "ILK & β1 integrin K.O.") with a homozygous deletion of Ilk and heterozygous deletion of Itgb1 in endothelial cells, and a LSM image of a stained cross-section through its jls/pTD. Scale bars: 500 and 100 µm, respectively. E-H LSM images of cross-sections through the jls/pTD of E13.5 control and ILK & β1 integrin K.O. embryos stained for the proliferation marker phospho-Histone H3. Arrows point to phospho-Histone H3-positive LEC",
    "ncbi_link": "Cre: 2777477
Ilk: 16202
ILK: 16202
Itgb1: 16412
β1 integrin: 16412
Flk1: 16542"
  },
  {
    "caption": "LSM images of PLA dots composed of VEGFR3 and phosphorylated tyrosine (p-Tyr) on stained cross-sections through the jls/pTD of control and ILK & β1 integrin K.O. embryos. Arrows point to PLA dots within the Lyve1 stained area. Scale bars: 10 µm",
    "ncbi_link": "ILK: 16202
β1 integrin: 16412"
  },
  {
    "caption": "Number of LECs per jls/pTD section in E13.5 control or ILK & β1 integrin K.O. embryos",
    "ncbi_link": "ILK: 16202
β1 integrin: 16412"
  },
  {
    "caption": "LEC proliferation as determined by the number of phospho-Histone H3-positive LECs per jls/pTD section in E13.5 control or ILK & β1 integrin K.O. embryos",
    "ncbi_link": "ILK: 16202
β1 integrin: 16412"
  },
  {
    "caption": "Quantification of the PLA dots indicating VEGFR3 with phosphorylated tyrosine (p-Tyr) per LEC of E13.5 control or ILK & β1 integrin K.O. embryos",
    "ncbi_link": "ILK: 16202
β1 integrin: 16412"
  },
  {
    "caption": "LSM images of a whole mount stained adult Prox1-CreERT2;Ilk+/+ mouse ear (referred to as "Adult Control") and Prox1-CreERT2;Ilk∆/∆ mouse ear (referred to as "Adult ILK K.O."), with higher magnification images indicated by dashed lines. Scale bars: 500 and LSM images of a whole-mount stained adult control and ILK K.O. ear, with higher magnification images indicated by dashed lines. Arrows point to proliferating LECs. Scale bars: 100 and 20 µm, respectively",
    "ncbi_link": "Cre: 2777477
ER: 13982
Ilk: 16202
ILK: 16202
Prox1: 19130"
  },
  {
    "caption": "Dermal lymph vessel density as determined by VEGFR3-positive area normalised to the total analysed area of adult control or ILK K.O. mice (n = 4 control and n = 5 ILK K.O. mice),",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "LEC proliferation as determined by phospho-Histone H3-positive LECs normalised to analysed VEGFR3-positive area in the skin of adult control or ILK K.O. mice (with n = 7 control and n = 5 ILK K.O. mice),",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "VEGFR3 tyrosine phosphorylation as determined by ELISA of skin lysates of adult control or ILK K.O. mice (n = 3 mice per genotype)",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "LSM images of a whole mount stained adult control and ILK K.O. cornea, with detailed images on their right (L\", M\"). Arrows point to lymph vessels protruding into the cornea (encircled by a dotted line). Scale bars: 500 µm and 100 µm, re Number of lymph vessels in control or ILK K.O. corneas (n = 5 and n = 7 corneas),",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "LSM images of cross-sections through the heart of an adult Prox1-CreERT2;Ilk+/+ mouse (referred to as "Adult Control") and Prox1-CreERT2;Ilk∆/∆ mouse (referred to as "Adult ILK K.O.") showing the outer lateral region of the left ventricle (LV) Overall cardiac lymph vessel and blood vessel density in heart sections as determined by Lyve1-positive and CD31-positive area (normalised to total analysed myocardial area), respectively (n = 4 control and n = 5 ILK K.O. mice)",
    "ncbi_link": "Cre: 2777477
ER: 13982
Ilk: 16202
ILK: 16202
Prox1: 19130"
  },
  {
    "caption": "LSM images of cross-sections through the heart of an adult control and ILK K.O. mouse four weeks after myocardial ischemia and reperfusion (MI/R), showing the outer lateral region of the LV. Scale bars: 100 µm Overall cardiac lymph vessel and blood vessel density in heart sections as determined by Lyve1-positive and CD31-positive area (normalised to total analysed myocardial area), respectively. (n = 5 control and n = 7 ILK K.O. mice), P = 0.051 (cardiac lymph vessel density in adult control versus adult ILK K.O.), *P = 0.025 (cardiac blood vessel density in adult control versus adult ILK K.O.)",
    "ncbi_link": "ILK: 16202"
  },
  {
    "caption": "Images of adult human LECs after 1 hour of BrdU incorporation and previous transfections with control or ILK siRNA. Scale bars: 50 µm",
    "ncbi_link": "ILK: 3611"
  },
  {
    "caption": "LEC proliferation as determined by the number of BrdU-positive cells normalised to the total number of LECs previously transfected with control siRNA or ILK siRNAs in the presence of VEGF-C Cys156Ser (n = 3 independent transfections per siRNA), *P = 0.032 (control versus ILK-1), *P = 0.005 (control versus ILK-2), *P = 0.0003 (control versus ILK-3)",
    "ncbi_link": "ILK: 3611"
  },
  {
    "caption": "VEGFR3 tyrosine phosphorylation as determined by ELISA of lysates from adult human LECs transfected with control siRNA or ILK siRNAs in the presence of VEGF-C Cys156Ser (n = 4 (control siRNA, ILK-1 siRNA, and ILK-3 siRNA), or n = 8 (ILK-2 siRNA) independent transfections per siRNA), *P = 0.0001 (control versus each siRNA)",
    "ncbi_link": "ILK: 3611"
  },
  {
    "caption": "LSM images of VEGFR3/β1 integrin PLA dots in human LECs transfected with control or ILK siRNA. Scale bars: 10 µm Quantification of VEGFR3/β1 integrin PLA dots per human LEC after transfection with control siRNA or ILK siRNAs (n = 5 independent transfections per siRNA), P = 0.234 (control versus ILK-1), *P = 0.024 (control versus ILK-2), *P = 0.001 (control versus ILK-3)",
    "ncbi_link": "ILK: 3611"
  },
  {
    "caption": " Western blot analysis of Shp2 in control and Shp2 ko cells. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " Immunofluorescence analysis of Ki67 on control and Shp2 ko cells at day 7. Scale bar, 50 μm. Quantification of the numbers of Ki67+cells shown in (C). Error bars represent SEM (n = 3). **P 0.01. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " phere formation by control and Shp2 ko cells at day 7. Scale bar, 200 μm. Quantification of the numbers of spheres formed by control and Shp2 ko cells shown in (E). Error bars represent SEM (n = 3). **P 0.01. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " Growth kinetics of spheres formed by control and Shp2 ko cells by counting sphere cells at day 4, 7, and 12. Error bars represent SEM (n = 3). ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " SA‐β‐gal staining on spheres formed by control and Shp2 ko cells at day 7. Scale bar, 100 μm. Quantification of the numbers of senescent cells in the spheres shown in (H). Error bars represent SEM (n = 3). **P 0.01. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " Western blot analysis of H3K9me3, p27, p53 pS18 (Ser18‐phosphorylated p53), total p53, Shp2, and α‐tubulin in control and Shp2 ko cells. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": " SA‐β‐gal staining on spheres formed by control cells and those treated by the Shp2 inhibitor GS493 at 15 μM at day 7. Scale bar, 100 μm. Quantification of the numbers of senescent cells shown in (K). Error bars represent SEM (n = 3). **P 0.01. Quantification of the numbers of spheres formed by control cells and those treated by the Shp2 inhibitor GS493 at 15 μM. Error bars represent SEM (n = 3). **P 0.01. Statistical significance was assessed by Student's unpaired t‐test. ",
    "ncbi_link": "Shp2: 5781///19247"
  },
  {
    "caption": " qRT-PCR analysis of mRNA levels of Skp2, Aurka, Dll1, and Hey1 in control, Shp2 ko, and Shp2‐inhibited cells. Error bars represent SEM (n = 3). ",
    "ncbi_link": "Aurka: 20878
Dll1: 13388
Hey1: 15213
Shp2: 19247
Skp2: 27401"
  },
  {
    "caption": " SA‐β‐gal staining on control, Shp2 ko, and Shp2 ko cells with overexpression of Skp2, Aurka, or N3IC cDNA. Scale bar, 100 μm. Quantification of the numbers of senescent cells shown in (C). Error bars represent SEM (n = 3). **P 0.01; ***P 0.001. Quantification of the numbers of spheres formed by cells shown in (C). Error bars represent SEM (n = 3). *P 0.05; **P 0.01; and ***P 0.001. Statistical significance was assessed by Student's unpaired t‐test. ",
    "ncbi_link": "Aurka: 20878
N3IC: 18131
Shp2: 5781///19247
Skp2: 27401"
  },
  {
    "caption": " SA‐β‐gal staining on control, Shp2 ko, and Shp2 ko cells with shRNA knockdown of p27 or p53. Scale bar, 50 μm. Quantification of the numbers of senescent cells shown in (A). Error bars represent SEM (n = 3). **P 0.01. Quantification of the numbers of spheres formed by cells shown in (A). Error bars represent SEM (n = 3). **P 0.01. ",
    "ncbi_link": "p27: 12576
Shp2: 5781///19247
p53: 7157///22059"
  },
  {
    "caption": " Western blot analysis of p27, p53, and α‐tubulin in control, Shp2 ko, and Shp2 ko cells with overexpression of Skp2, Aurka, or N3IC cDNAs. The numbers below indicate the relative ratios of band intensities between p27 and α‐tubulin or between p53 and α‐tubulin. ",
    "ncbi_link": "Aurka: 20878
N3IC: 18131
Shp2: 5781///19247
Skp2: 27401"
  },
  {
    "caption": " Western blot analysis of p27, p53, and α‐tubulin in PyMT cells treated with control (DMSO) or inhibitors against Skp2 (MLN4924), Aurora A (VX‐680), or Notch (DAPT) at the indicated concentrations. The numbers below indicate the relative ratios of band intensities between p27 and α‐tubulin or between p53 and α‐tubulin. ",
    "ncbi_link": "Aurora A: 20878
Notch: 18131///18129///18128
Skp2: 27401"
  },
  {
    "caption": " Quantification of the numbers of senescent cells in PyMT cells treated with control, MLN4924, MLN4924 plus p27 knockdown or MLN4924 plus p53 knockdown. Error bars represent SEM (n = 3). **P 0.01; NS, not significant. ",
    "ncbi_link": "p27: 12576
p53: 7157///22059"
  },
  {
    "caption": " Quantification of the numbers of senescent cells in PyMT cells treated with control, VX‐680, VX‐680 plus p27 knockdown, or VX‐680 plus p53 knockdown. Error bars represent SEM (n = 3). *P 0.05; NS, not significant. ",
    "ncbi_link": "p27: 12576
p53: 7157///22059"
  },
  {
    "caption": " Quantification of the numbers of senescent cells in PyMT cells treated with control, DAPT, DAPT plus p27 knockdown, or DAPT plus p53 knockdown. Error bars represent SEM (n = 3). **P 0.01; NS, not significant. Statistical significance was assessed by Student's unpaired t‐test. ",
    "ncbi_link": "p27: 12576
p53: 7157///22059"
  },
  {
    "caption": " SA‐β‐gal staining on MLN4924 tumorcells treated with control, Shp2 inhibitor GS493 (15 μM), Src inhibitor PP2 (2.5 μM), Fak inhibitor TAE226 (0.5 μM), or Mek1 inhibitor U0126 (20 μM). Scale bar, 100 μm. ",
    "ncbi_link": "Mek1: 26395
Fak: 14083
Shp2: 5781///19247
Src: 20779"
  },
  {
    "caption": " qRT-PCR analysis of mRNA levels of Skp2, Aurka, Dll1, and Hey1 in control cells and those treated with the indicated inhibitors. Error bars represent SEM (n = 3). ",
    "ncbi_link": "Aurka: 20878
Dll1: 13388
Hey1: 15213
Skp2: 27401"
  },
  {
    "caption": " A Kaplan-Meier survival analysis of humanpatients (n = 3,935) with invasive breast cancers divided into two groups based on the gene expression level of Shp2 (see ). ",
    "ncbi_link": "Shp2: 5781"
  },
  {
    "caption": " B-D Kaplan-Meier survival analyses of the humanpatients (n = 3,935) divided into two groups based on the expression level of the genes of each overrepresented class determined in Fig A: cell cycle genes, DNA replication genes, or p53 target genes. ",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": " B-D Kaplan-Meier survival analyses of the humanpatients (n = 3,935) divided into two groups based on the expression level of the genes of each overrepresented class determined in Fig A: cell cycle genes, DNA replication genes, or p53 target genes. ",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": " E, F Kaplan-Meier survival analyses of humanpatients (n = 3,935) divided into two groups based on the gene expression level of Skp2 or Aurka. HR, hazard ratio. ",
    "ncbi_link": "Aurka: 20878
Skp2: 27401"
  },
  {
    "caption": "  Kaplan-Meier analyses of tumor formation for control (MLN4924;Shp2fl/fl, blue, n = 33), heterozygous Shp2 mutant (MLN4924;MMTV‐Cre;Shp2+/fl, green, n = 15), and homozygous Shp2 mutant (MLN4924;MMTV‐Cre;Shp2fl/fl, also called MLN4924;coShp2, orange, n = 34) mice. ***P 0.001 (log‐rank test). ",
    "ncbi_link": "Cre: 
Shp2: 19247"
  },
  {
    "caption": " Mammary gland whole‐mounts from control MLN4924 and MLN4924;MMTV‐Cre;Shp2fl/flmice at indicated ages. The characteristic lymph node of the mammary glandfat pad is marked by white arrowheads; premalignant lesions are marked by red arrowheads. Scale bar, 4 mm. Quantification of premalignant lesions in mammary glands of control MLN4924 and MLN4924;MMTV‐Cre;Shp2fl/flmice, as shown in (B). Error bars represent SEM (n = 6). *P 0.05 (Student's unpaired t‐test). ",
    "ncbi_link": "Cre: 
Shp2: 19247"
  },
  {
    "caption": " Immunostaining of EYFP and CK8 on mammary gland sections from MLN4924;MMTV‐Cre;Shp2+/fl;EYFP−/fl and MLN4924;MMTV‐Cre;Shp2fl/fl;EYFP−/flmice at hyperplasia, adenoma, and carcinoma stages. Scale bar, 100 μm. n = 8. ",
    "ncbi_link": "Cre: 
Shp2: 5781///19247"
  },
  {
    "caption": " Immunohistochemistry analysis of Cre recombinase on paraffin sections of primary tumors (top) and metastases (bottom) from MLN4924;Shp2fl/fl, MLN4924;MMTV‐Cre;Shp2+/fl, and MLN4924;MMTV‐Cre;Shp2fl/flmice. Scale bar, 100 μm. n = 8. ",
    "ncbi_link": "Cre: 
Shp2: 5781///19247"
  },
  {
    "caption": " qRT-PCR analyses of Shp2mRNA levels in tumor tissues from MLN4924;Shp2fl/fl (n = 8), MLN4924;MMTV‐Cre;Shp2+/fl (n = 6), and MLN4924;MMTV‐Cre;Shp2fl/fl (n = 6) mice. Error bars represent upper and lower quartiles. ",
    "ncbi_link": "Cre: 
Shp2: 5781///19247"
  },
  {
    "caption": " Western blot analysis of Shp2protein levels in tumor tissues from MLN4924;Shp2fl/fl, MLN4924;MMTV‐Cre;Shp2+/fl, and MLN4924;MMTV‐Cre;Shp2fl/flmice. ",
    "ncbi_link": "Cre: 
Shp2: 5781///19247"
  },
  {
    "caption": " Immunohistochemistry analysis of EYFP (top) and SA‐β‐gal staining (bottom) on cryosections of mammary glandtumors from control MLN4924;Shp2fl/fl;EYFP−/fl, MLN4924;MMTV‐Cre;Shp2+/fl;EYFP−/fl, and MLN4924;MMTV‐Cre;Shp2fl/fl;EYFP−/flmice. Note that SA‐β‐gal activity was present in the EYFP‐positive (Shp2‐negative) areas (right, arrows) and was absent in the EYFP‐negative (Shp2‐positive) areas (right, arrowhead) of mammary glandtumors of MLN4924;MMTV‐Cre;Shp2fl/fl;EYFP−/flmice. Consecutive sections of EYFP and SA‐β‐gal staining for each group are shown. Scale bar: 100 μm. n = 5. ",
    "ncbi_link": "Cre: 
Shp2: 19247"
  },
  {
    "caption": " Immunofluorescence analysis of Ki67, EYFP and CK8 (pan‐epithelial marker) (top panel), p27 and EYFP (middle panel), and p53 and EYFP (bottom panel) on cryosections of mammary glandtumors from control MLN4924;Shp2fl/fl;EYFP−/fl, MLN4924;MMTV‐Cre;Shp2+/fl;EYFP−/fl, and MLN4924;MMTV‐Cre;Shp2fl/fl;EYFP−/flmice. DAPI was used for nuclear counterstain. Ki67 was absent in EYFP‐positive cells (top right, arrows) and was present in EYFP‐negative cells (top right, arrowheads); p27 was present in EYFP‐positive cells (middle right, arrows) and was absent in EYFP‐negative cells (middle right, arrowhead); and p53 was present in EYFP‐positive cells (bottom right, arrows) and was absent in EYFP‐negative cells (bottom right, arrowhead). Scale bar: top panel, 100 μm; middle and bottom panel, 50 μm. n = 5. ",
    "ncbi_link": "Cre: 
Shp2: 5781///19247"
  },
  {
    "caption": " qRT-PCR analysis of mRNA levels of Shp2, Skp2, Aurka, Dll1, and Hey1 in EYFP+ and EYFP−cells isolated by FACS from MLN4924;MMTV‐Cre;Shp2fl/fl;EYFP−/fltumors. Error bars represent SEM (n = 5). ",
    "ncbi_link": "Cre: 
Aurka: 20878
Dll1: 13388
Hey1: 15213
Shp2: 19247
Skp2: 27401"
  },
  {
    "caption": " Kaplan-Meier analysis of tumor formation in control (blue, n = 8) and GS493‐pretreated (red, n = 8) MLN4924;MMTV‐Cre;Shp2fl/flmice. The bar indicates the duration of treatment. ",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": "(B) Volcano plot of a genome-wide association using mixed-model linear regression of antimycin A resistance for 118,527 genetic variants. Variants with moderate or high impact are shown in blue. Red dot: the variant at locus I:3845516, which causes a T343A change in the Pyk1 amino-acid sequence. This variant was among the top scoring (effect size=-0.645, rank 34; p=0.0008, rank 70).",
    "ncbi_link": "Pyk1: 2543557"
  },
  {
    "caption": "(C) Boxplot showing antimycin A resistance for 154 strains grouped by the two alleles at the pyk1 locus. Strains carrying a C at this genomic locus (orange box) generally have higher antimycin resistance than strains carrying the reference allele T (blue box). As is standard, this boxplot and all other boxplots in this manuscript show the median of the data as central line, the quartiles as box and the extend of the rest of the distribution as whiskers. Points which are 1.5 times the inter-quartile range beyond the high and low quartiles are considered outliers and shown individually.",
    "ncbi_link": "pyk1: 2543557"
  },
  {
    "caption": "(B) Left boxplot: two glycolytic intermediates directly upstream of PYK were strongly depleted in the A-strain (nT-strain=9, nA-strain=8). Right barplot: PYK activity was directly measured using a lactate dehydrogenase-coupled colorimetric enzyme activity assay, showing the mean and standard deviation of substrate conversion rate for 3 biological replicates, each measured in technical duplicates. Data information: Significance keys: * p<0.05, ** p<0.005, *** p<0.0005 (Welch's t-test)",
    "ncbi_link": "PYK: 2543557"
  },
  {
    "caption": "(G) Boxplot showing resistance to 3mM H2O2 grouped by pyk1 allele for 156 strains from our collection. The T-strains had a higher mean fitness in H2O2 than the A-strains (1.01±0.06 vs 0.95±0.11; p=0.0021, Welch's t-test). The resistance score was obtained as for antimycin A.",
    "ncbi_link": "pyk1: 2543557"
  },
  {
    "caption": "(H) Boxplot showing growth fitness on rich media, grouped by pyk1 allele for 158 S. pombe strains (0.88±0.16 vs 0.94±0.24; p=0.18, Welch's t-test).",
    "ncbi_link": "pyk1: 2543557"
  },
  {
    "caption": "(C,D) Normalized gene expression levels (read count normalized for each cell, log2) in different tissues, from the scRNA-seq experiment, for a TATA group gene, and a highly paused group gene, are shown. (C) The TATA gene, Ccp84Aa, shows noisy expression in the epidermis, without detectable background expression in non-expressing tissues. (D) The highly paused gene, Gip, shows very robust expression in crystal cells, but has high background expression in the non-expressing tissues.",
    "ncbi_link": "Ccp84Aa: 40825
Gip: 31960"
  },
  {
    "caption": "C, D) ATAC-seq chromatin accessibility was measured in different tissues isolated from 14-17 h embryos using INTACT. (C) Read-count normalized ATAC (RPM) signal at individual genes from the TATA group (Ccp84Aa) and highly paused gene group (ect) are shown. (D) Read-count normalized ATAC signals (RPM) from different tissues were calculated for each gene from 150 bp upstream of the TSS to the TSS. Paused genes show higher average accessibility across all tissues compared to the TATA genes (Wilcoxon two-sided test, *P <2.2*10-16).",
    "ncbi_link": "Ccp84Aa: 40825
ect: 44135"
  },
  {
    "caption": "B N-terminally GFP-tagged 50Q was checked for its autophagic degradation in indicated yeast cells by GFP processing assays after 1, 4 and 16 h starvation. Yeast cells with ATG1 deletion were used as positive controls.",
    "ncbi_link": "ATG1: 852695"
  },
  {
    "caption": "H Vacuole localization and degradation of endocytosis substrate GFP-Sna3 in WT, atg1∆ and rpb9∆ cells. Scale bars: 5 μm.",
    "ncbi_link": "atg1: 852695
rpb9: 852810"
  },
  {
    "caption": "I Carboxypeptidases Y (Cpy1), a vacuolar-resident hydrolases, was analyzed for its transporting to vacuoles by the secretory pathway in WT, atg1∆ and rpb9∆ cells.",
    "ncbi_link": "atg1: 852695
rpb9: 852810"
  },
  {
    "caption": "E-I Overexpression of ATG1 could partially restore autophagy in rpb9∆ cells. ATG1, ATG9, ATG13, ATG17 and ATG5 were overexpressed in rpb9∆ yeast cells, GFP-50Q was checked for its autophagic degradation by GFP processing assays after 1, 4 and 16 h starvation.",
    "ncbi_link": "ATG1: 852695
ATG13: 856315
ATG17: 851142
ATG5: 855954
ATG9: 851406
rpb9: 852810"
  },
  {
    "caption": "B Indicated Rpb9 truncates and mutants were expressed in rpb9∆ cells and autophagic degradation of GFP-50Q was checked by GFP-processing assays.",
    "ncbi_link": "Rpb9: 852810
rpb9: 852810"
  },
  {
    "caption": "F-G Neither overexpression of Gcn4 in rpb9∆ yeast cells nor overexpression of Rpb9 in gcn4∆ yeast cells can restore autophagy. Gcn4 or Rpb9 were overexpressed in rpb9∆ or gcn4∆ yeast cells respectively and autophagic degradation of GFP-50Q was detected.",
    "ncbi_link": "Gcn4: 856709
gcn4: 856709
rpb9: 852810
Rpb9: 852810"
  },
  {
    "caption": "C Rpb9 orthologs from complex eukaryotic species could restore autophagy in rpb9∆ yeast cells. Indicated Rpb9 orthologs were expressed in rpb9∆ yeast cells and autophagic degradation of GFP-50Q was detected.",
    "ncbi_link": "Rpb9: 69920
Rpb9: 5438
rpb9: 852810"
  },
  {
    "caption": "D N-terminal Zinc finger domain and linker region of Rpb9 orthologs from different species could restore autophagy defects in rpb9∆ yeast cells. Indicated truncates of Rpb9 orthologs were expressed in rpb9∆ yeast cells and autophagic degradation of GFP-50Q was detected.",
    "ncbi_link": "Rpb9: 69920
Rpb9: 5438
rpb9: 852810"
  },
  {
    "caption": "A. Representative plots of splenocytes from CD45.1 mice adoptively transferred with CD45.2 OT-II WT or CCR5-/- lymph node cell suspensions, five weeks after infection with rVACV-OVA virus. The gating strategy used to identify the memory CD4+ T cell subtypes is shown (n = 5).",
    "ncbi_link": "CCR5: 12774
OVA: 396058
CD45.1: 19265
CD45.2: 19265"
  },
  {
    "caption": "C, Percentage of CD4+ TEM (C) in the OT-II WT and CCR5-/- populations (n = 5).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "D. Percentage of TCM (D) in the OT-II WT and CCR5-/- populations (n = 5).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "E. IFNγ-producing OT-II WT and CCR5-/- memory cells isolated from mice as in A and restimulated ex vivo with OVA323-339 (1 μM) (n = 4).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "A, Representative histograms and quantification of mean fluorescence intensity (MFI; A) in OT-II WT and CCR5‑/‑ lymphoblasts expanded in IL-2 or IL-15, as specified. Data shown as mean ± SEM (n ≥3).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "B. the percentage of cells positive for the indicated memory markers (B) in OT-II WT and CCR5‑/‑ lymphoblasts expanded in IL-2 or IL-15, as specified. Data shown as mean ± SEM (n ≥3).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "A-C. Analysis of TCR nanoclustering by EM in OT-II WT and CCR5-/- naïve cells (A; n = 6 cells/genotype; WT: 3427, CCR5-/-: 3528 particles), and IL-2- (B; WT, n = 8 cells, 15419 particles; CCR5-/-, n = 6 cells, 5410 particles) or IL-15-expanded lymphoblasts (C; WT, n = 8 cells, 27518 particles; CCR5-/-, n = 7 cells, 22696 particles). A representative small field image at the top of each panel shows gold particle distribution in the cell surface replicas of anti-CD3ε-labeled cells; at bottom, quantification (mean ± SEM) of gold particles in clusters of indicated size in WT (gray bars) and CCR5-/- cells (red). Insets show the distribution of clusters of one, two, three, four, or more than four particles, and statistical analysis.",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "D, E. Posterior distribution in naïve (D) and IL-2-expanded lymphoblasts (E) of the clustering parameter b for WT (gray) and CCR5-/- cells (red); randomly generated distributions of receptors are shown in blue. The mean value of the b parameter is indicated for each condition. The probability of a chance distribution similar to that determined in cells is nearly 0% by the ROPE.",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "F. Comparison of TCR oligomer size using BN-PAGE and anti-CD3ζ immunoblotting in day 10, IL-2-expanded WT and CCR5-/- OT-II lymphoblasts lysed in buffer containing digitonin or Brij-96. The marker protein is ferritin (f1, 440 and f2, 880 kDa forms). The ratio of TCR nanoclusters to monomeric TCR in each lysis condition was quantified by densitometry (right; n = 5).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "G. Top, representative small field EM images showing gold particle distribution in the cell surface replicas of CD4+ T cells isolated from OVA/OVA-immunized WT and CCR5-/- mice. Bottom, quantification (mean ± SEM) of gold particles in clusters of the indicated size (WT, gray bars; n = 5 cells, 14680 particles; CCR5-/-, red; n = 7 cells, 15374 particles). Insets show the distribution between clusters of one, two, three, four or more than four particles, and statistical analysis.",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "A. Total Chol levels in WT and CCR5-/- OT-II lymphoblasts (day 10, IL-2-expanded) as determined by a fluorometric assay (n = 6).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "B-D. SM (B), Cer (C) and dhCer (D) levels in WT and CCR5-/- OT-II 10-day lymphoblasts, as determined by UPLC-TOF MS. Values, after normalization with C17 standards and cell number in each sample, are the mean of two independent experiments (n = 6).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "E. RT-qPCR determination of CerS mRNA levels in naïve and IL-2-expanded WT and CCR5‑/- OT-II 10-day lymphoblasts (n = 3-5).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "F. Representative immunoblot showing CerS2 protein levels in naïve and WT and CCR5-/- OT-II 10-day lymphoblasts, and densitometric quantification of blots as above (n = 10).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "G. ChIP analysis of the CerS2 promoter using an anti-H3K9Ac antibody. Scheme of the CerS2 promoter showing CpG islands and primers used for amplification. Relative ChIP of the CerS2 promoter in WT and CCR5-/- OT-II 10-day lymphoblasts (n = 3).",
    "ncbi_link": "CCR5: 12774
CerS2: 76893"
  },
  {
    "caption": "H. Relative CerS2 mRNA level in CD4 T cells treated with PTx (n = 3).",
    "ncbi_link": "CerS2: 76893"
  },
  {
    "caption": "L. Representative immunofluorescence images showing pSer142-GATA-1 staining (green) of OT-II WT and CCR5-/- lymphoblasts. The green channel (top) and the merge with nuclear DAPI staining (blue; bottom) are shown. Scale bar, 10 μm. M. Quantification of nuclear staining of the cells plotted as integrated density fluorescence intensity in DAPI-stained area; n ≥50 cells/condition).",
    "ncbi_link": "CCR5: 12774"
  },
  {
    "caption": "N. Top, basic scheme of the CerS2 promoter, indicating the putative GATA-1 binding site (blue) and location of the primers used for amplification in ChIP assays (black arrows). Bottom, relative anti-GATA-1 ChIP levels in OT-II WT and CCR5-/- lymphoblasts (n = 5).",
    "ncbi_link": "CCR5: 12774
CerS2: 76893"
  },
  {
    "caption": "F. GFP expression in shCtrl- (black) and shCerS2 (orange)-transduced 2B4 cells after puromycin selection, as determined by FACS.",
    "ncbi_link": "GFP: 
CerS2: 76893"
  },
  {
    "caption": "G. Relative CerS2 mRNA levels in TAK-779-treated 2B4 cells as in F. Values were normalized to those obtained in untransduced TAK-779-treated 2B4 cells (n = 3).",
    "ncbi_link": "CerS2: 76893"
  },
  {
    "caption": "H. Representative immunoblot with anti-CerS2 antibody to determine CerS2 protein levels in shCtrl and ShCerS2-transduced 2B4 cells as in G. Filters were rehybridized with β-actin as loading control.",
    "ncbi_link": "CerS2: 76893"
  },
  {
    "caption": "I. TCR nanoclustering of shCtrl- and shCerS2 transduced 2B4 cells in the presence of TAK-779 as determined by EM. Representative small field images and quantification (mean ± SEM) of gold particles in clusters of indicated sizes in cell surface replicas shCtrl (gray black bars; n = 6 cells, 12337 particles) and shCerS2 2B4 lymphoblasts (orange; n = 7 cells, 13456 particles). Inset, distribution between clusters of indicated size and statistical analysis.",
    "ncbi_link": "CerS2: 76893"
  },
  {
    "caption": "J. Percentage of CD69+ shCtrl (black) and shCerS2 (orange) 2B4 cells restimulated with plate-bound anti-CD3ε antibody in the presence of TAK-779 (n = 3).",
    "ncbi_link": "CerS2: 76893"
  },
  {
    "caption": "A. Analysis of TCR nanoclustering in lymphoblasts from healthy WT and ccr5Δ32 homozygous donors by EM. Top, representative small field image showing gold particle distribution in cell surface replicas of anti-CD3ε-labeled cells; bottom, quantification (mean ± SEM) of gold particles in clusters of the indicated size in the WT (gray bars; n = 5 cells, 17689 particles) and Δ32/Δ32 cells (light red; n = 4 cells, 16938 particles). Insets show the distribution between clusters of one, two, three, four or more than four particles, and statistical analysis.",
    "ncbi_link": "ccr5: 12774"
  },
  {
    "caption": "C. Relative CerS2 mRNA levels in day 8 WT and ccr5Δ32 lymphoblasts. Each data point is the average of a technical triplicate from 3 donors in two independent experiments (n = 6)",
    "ncbi_link": "ccr5: 12774
CerS2: 76893"
  },
  {
    "caption": "A, B. RT-qPCR analysis of Zfp207 and Oct4 in mouse ESCs during (A) retinoic acid (RA)-induced and (B) embryoid body (EB)-mediated differentiation. Nestin was used as a neuronal differentiation marker to monitor RA-mediated differentiation. mRNA levels are relative to the expression at day 0.",
    "ncbi_link": "Nestin: 18008
Oct4: 18999
Zfp207: 22680"
  },
  {
    "caption": "J, K. (J) AP staining of shScr and Zfp207-depleted (sh1 and sh2) mouse ESCs. Scale bars, 20 µM. (K) Percentage of fully differentiated (FD), partially differentiated (PD) and undifferentiated (UN) ESC colonies in shScr, sh1 and sh2.",
    "ncbi_link": "Zfp207: 22680"
  },
  {
    "caption": "M, N. (M) Western blot of ZFP207, OCT4, NANOG, and SOX2 in shScr, sh1 and sh2 ESCs and (N) RT-qPCR analysis of Oct4, Nanog, and Sox2 in shScr, sh1 and sh2 ESCs; data is relative to shScr.",
    "ncbi_link": "Nanog: 71950
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "D. RT-qPCR of Zfp207, the pluripotency genes (Oct4, Nanog and Sox2), the mesodermal markers (Msx1 and Brachyury, T), the endodermal markers (Foxa2, Sox17), and the neural-associated genes (Pax6, Sox11 and Nestin) in shScr, sh1 and sh2 ESCs along the time-course of EB-mediated differentiation. mRNA levels are relative to the expression of shScr at day 0.",
    "ncbi_link": "Foxa2: 15376
Msx1: 17701
Nanog: 71950
Nestin: 18008
Pax6: 18508
Oct4: 18999
Sox11: 20666
Sox17: 20671
Sox2: 20674
Brachyury: 20997
T: 20997
Zfp207: 22680"
  },
  {
    "caption": "G. RT-qPCR of Zfp207 and neural-associated markers in shScr, sh1 and sh2 along the course of neural differentiation. mRNA levels are relative to shScr at day 0.",
    "ncbi_link": "Zfp207: 22680"
  },
  {
    "caption": "(A) Volcano plots of common differentially expressed genes in shScr and Zfp207-depleted (sh1 and sh2) mouse ESCs. Up-regulated (Up) and down-regulated (Down) genes are indicated in red and blue, respectively (p < 0.05; > 1.5-fold). Zfp207 is depicted in black. Grey dots indicate non-significant (NS) and < 1.5-fold differential expressed genes.",
    "ncbi_link": "Zfp207: 22680"
  },
  {
    "caption": "F. RT-PCR of Zfp207-regulated AS events. For Mta1, AS1 (alternative splicing 1) and AS2 (alternative splicing 2). #1 and #2 indicate distinct biological replicates. *Denotes an isoform that was not taken in consideration for the quantification. The structure of each isoform is indicated (not to scale). Alternative exons are blue. The percent spliced in (PSI) was quantified for each condition.",
    "ncbi_link": "Mta1: 116870
Zfp207: 22680"
  },
  {
    "caption": "(I) Scanning confocal microscopy analysis of Saos2 WT and CRISPR-Cas9 IDUA Saos2 at steady state, immunolabeled for PC1 and LAMP1. Nuclei were stained with Hoechst. Scale bar = 10 µm. The insets show higher magnification (left = x3.09; right = x3.12) and single colour channels of the boxed area. Bar graph shows quantification of lysosomes containing PC1 expressed as % of total LAMP1 per cell (mean +/- SEM). n= 31 WT cells, n=33 CRISPR cells counted; 3 independent experiments. Student's unpaired, two-tailed T-Test *** P<0.0001.",
    "ncbi_link": "IDUA: 3425"
  },
  {
    "caption": "(J) WT and CRISPR IDUA Saos2 lysed and analysed by western blot. Data are representative of 3 independent experiments.",
    "ncbi_link": "IDUA: 3425"
  },
  {
    "caption": "(D) Correlative Light Electron Microscopy (CLEM) and Electron Tomography of Saos2 cells transfected with GFP-LC3 (green) and labelled for PC1 (568, red and nanogold particles) and CANX (647, blue). Cells were first imaged by confocal microscopy (top left panel) and then the same region was retraced in EM (upper middle panel) and overlay is shown (upper right panel). Arrow indicates a LC3 positive vesicle containing CANX and PC1 molecules.",
    "ncbi_link": "LC3: 84557"
  },
  {
    "caption": "(A) WT and CRISPR-Cas9 Fam134b knockout MEFs were treated as indicated, lysed and analysed by western blot with the indicated antibodies. Western blots are representative of 4 independent experiments.",
    "ncbi_link": "Fam134b: 66270"
  },
  {
    "caption": "(B) WT and CRISPR-Cas9 Fam134b MEFs were immunolabeled for PC1 (568, red), nuclei stained with Hoechst (blue) and analysed by scanning confocal microscopy. Scale bar = 10 µm.",
    "ncbi_link": "Fam134b: 66270"
  },
  {
    "caption": "(C) CRISPR FAM134B MEF mock, wild type FAM134B-HA or FAM134Blir-HA transfected were immunolabeled for PC1 (568, red), LAMP1 (488, green) and HA (647, violet) and analysed by scanning confocal microscopy. Scale bar = 10 µm. Inset panels show magnification of the boxed area. Bar graph shows quantification of LAMP1 vesicles positive for PC1, expressed as % of total lysosomes (mean +/- SEM), quantification of n=10 cells per treatment; 3 independent experiments. One-way ANOVA with Dunnett's multiple comparisons test was performed. ns ≥0.05, *** P<0.0001.",
    "ncbi_link": "FAM134B: 66270
FAM134B: 54463"
  },
  {
    "caption": "(B) WT and Canx-/- MEFs were untreated or treated with BafA1 (10 μM) for 6 h, lysed and analysed by western blot with indicated antibodies. Filamin and β-actin were used as loading control. Dashed line indicates that unnecessary lanes were removed. Western blot is representative of 3 independent experiments.",
    "ncbi_link": "Canx: 12330"
  },
  {
    "caption": "(A, B) Volcano plot comparing protein fold changes between WT versus Fam134b-/- (A) and WT versus Canx-/- MEFs (B). Significantly regulated proteins are labelled in red (log2 fold change > 1, -log10 p>1.3). Red dots with blue ring indicate collagen 1 peptides. Graphs represent statistics from three separate experiments for each genotype.",
    "ncbi_link": "Canx: 12330
Fam134b: 66270"
  },
  {
    "caption": "(B) U2OS cells were transfected with empty vector control (pcDNA3), FAM134B-HA WT or mutant constructs as indicated. Complexes were immune-isolated with HA-magnetic beads, separated by western blot and visualised with antibodies against CANX, FAM134B 5% of the input is shown. Western blots are representative of 3 independent experiments. Dashed line indicates that unnecessary lanes were removed.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "U2OS cells were transfected with HALO-PC2, FAM134B-HA or FAM134Blir-HA constructs, treated with 100 nM BafA1 for 6h and with CST where indicated. Complexes were immune-isolated with HA-magnetic beads, separated by western blot and visualised with antibodies against HALO, CANX, FAM134B, LC3 5% of the input is shown. Western blots are representative of 3 independent experiments. Dashed line indicates that unnecessary lanes were removed.",
    "ncbi_link": "PC2: 
FAM134B: 54463"
  },
  {
    "caption": "A‐C) Time‐lapse imaging of hepatoma cells infected with UIS4‐mCherry‐expressing Plasmodium berghei was used to determine the velocities of the UIS4‐positive features, e.g., a tubule (A), elongated membrane cluster (B) and vesicle (C) were tracked over time. Measured speeds of the dynamic features indicated with white arrows are depicted graphically to the right. Scale bars, 10 µm.",
    "ncbi_link": "UIS4: "
  },
  {
    "caption": "B) Cells infected with UIS4‐mCherry‐expressing parasites were treated with nocodazole for 1.5 h (top) or cytochalasin D for 30 min (bottom) and imaged by confocal microscopy. Imaging occurred 29 and 24 h post‐infection, respectively. UIS4‐positive tubules, static (top) and dynamic (bottom), are indicated with white arrowheads. Displayed cells are representative of five imaged parasites from at least two different experiments.",
    "ncbi_link": "UIS4: "
  },
  {
    "caption": "B) Cells infected with UIS4‐mCherry‐expressing parasites were treated with nocodazole for 1.5 h (top) or cytochalasin D for 30 min (bottom) and imaged by confocal microscopy. Imaging occurred 29 and 24 h post‐infection, respectively. UIS4‐positive tubules, static (top) and dynamic (bottom), are indicated with white arrowheads. Displayed cells are representative of five imaged parasites from at least two different experiments.",
    "ncbi_link": "UIS4: "
  },
  {
    "caption": "d. Real-time reverse transcription quantitative PCR (RT-qPCR) showing Fbxw7, Pten and Trp53 expression in mouse uteri at 4 weeks and 8 weeks postnatal age (NB Trp53R172H uteri were not analysed at the 4 week timepoint). Box extends from 25th to 75th percentiles, with line at median, whiskers indicate minimum and maximum values, and dots individual values (n=5 samples per group with exception of Ptendel and Ptendel, Fbxw7mut genotypes at 8 weeks which contain n=7 samples each). Statistical comparison between WT controls and other genotypes was performed by unadjusted, unpaired Mann Whitney test; * indicates P<0.05, ** indicates P<0.01",
    "ncbi_link": "Fbxw7: 50754
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "e. Western blot of mouse uteri at 8 weeks postnatal age (NB Trp53R172H uteri were not analysed by Western blotting). Values indicate densitometric units (mean ± SD) normalised to control group of WT samples in case of Fbxw7 protein and both WT and Fbxw7mut samples in case of Pten and p53 proteins. Image is representative of duplicate technical replicates. Statistical comparison between controls and other groups was performed by unadjusted, unpaired Mann Whitney test; and are shown next to densitometry results where statistically significant.",
    "ncbi_link": "Fbxw7: 50754
Trp53: 22059"
  },
  {
    "caption": "c. Low and high power images of GEMM uteri at 8 weeks age and at study endpoint after H&E staining or IHC for cytokeratin 8 (CK8) (epithelia). Scale bars in low and high magnification panels indicate 1000μm and 100μm respectively. Images are representative of a minimum of 5 mice per genotype per timepoint, with exception of wild-type and Fbxw7mut mice at 8 weeks age where 3 mice were analysed.",
    "ncbi_link": "Fbxw7: 50754"
  },
  {
    "caption": "e. H&E-stained sections of high grade external sarcomas in Trp53del, Trp53del; Fbxw7mut, Trp53mut and Trp53mut; Fbxw7mut mice. Images are representative of minimum of 3 mice examined for each genotype. Scale bar indicates 100μm.",
    "ncbi_link": "Fbxw7: 50754
Trp53: 22059"
  },
  {
    "caption": "a. (Left panel) Schematic illustrating gene expression profiling of mouse uterine samples of indicated genotypes and group sizes at 8 weeks age, with groups compared by enrichment analysis. (Right panel) Dot plot indicating enrichment of MSigDB C6 oncogenic gene sets in Ptendel; Fbxw7mut uteri vs Ptendel uteri. Arrows indicate enrichment of LEF1 signatures.",
    "ncbi_link": "Fbxw7: 50754
Pten: 19211"
  },
  {
    "caption": "a. HEK293T cells were transfected with constructs encoding FLAG-V5-tagged FBXW7α and Myc-tagged LEF1. FLAG-V5-tagged FBXW7 α was immunoprecipitated (IP) from cell extracts with anti-FLAG antibody before immunoblotting for tagged proteins as indicated (upper panels). Lower panels show inputs. b. HEK293T cells were transfected with constructs encoding FLAG-V5-tagged FBXW7α and Myc-tagged TCF7L2. IP was performed as in (a) before immunoblotting for tagged proteins as indicated. Data information: All images shown are representative of a minimum of two independent experiments",
    "ncbi_link": "FLAG: 
Myc: 
V5: 
FBXW7α: 55294
LEF1: 51176
TCF7L2: 6934"
  },
  {
    "caption": "g. HEK293T cells were transfected with Myc-tagged FBXW7α and either FLAG-V5-tagged full length LEF1 (FL) or truncated LEF1 in which the N terminal domain required for β-catenin binding has been deleted. Immunoblotting for indicated proteins was performed following IP by anti-FLAG antibody. Data information: All images shown are representative of a minimum of two independent experiments",
    "ncbi_link": "FLAG: 
Myc: 
V5: 
FBXW7α: 55294
LEF1: 51176"
  },
  {
    "caption": "a. Dot plot showing log2-transformed expression of FBXW7, LEF1 and other wnt pathway genes in endometrial epithelial cell subsets defined by single cell RNAseq (scRNAseq)",
    "ncbi_link": "FBXW7: 55294
LEF1: 51176"
  },
  {
    "caption": "d. Immunohistochemistry for LEF1 and β-catenin from endometrial carcinomas in Ptendel ± Fbxw7mut mice. High power images show representative staining in LEF1 negative and positive glands. Scale bar bar indicates 1000μm. ",
    "ncbi_link": "Fbxw7: 50754
Pten: 19211"
  },
  {
    "caption": "ISCts midguts expressing YFP alone (control), or expressing two non-overlapping EcR-RNAi, and quantification of the number of YFP-positive cells (yellow). The graph also plots the number of GFP-positive cells in esgts midgut expressing GFP alone (ctrl), or expressing EcR-RNAi#1, EcR-RNAi#2, and mcherry-RNAi as an additional negative control (see EV2B).",
    "ncbi_link": "GFP: 
EcR: 35540
esg: 34903"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing EcR-DN, and EcR-DN + pri. Samples were stained for GFP (green). The graph shows quantification of the number of GFP-positive cells in the different genotypes.",
    "ncbi_link": "GFP: 
EcR: 35540
esg: 34903"
  },
  {
    "caption": "Posterior midguts containing control and Ubr3 null MARCM clones (GFP, green).",
    "ncbi_link": "Ubr3: 31713"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing Ubr3-RNAi, and Ubr3-RNAi + OvoB. Samples were stained for GFP (green). H' quantification of GFP-positive cells from H.",
    "ncbi_link": "GFP: 
esg: 34903
OvoB: 31429
Ubr3: 31713"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control) or expressing SvbACT. Samples were stained for GFP (green), and ß-catenin (purple), DE-Cadherin (white) or Scribble (yellow). Top and bottom pictures show separate channels for a same region.",
    "ncbi_link": "GFP: 
Svb: 31429"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing miR8, OvoB, and mir8 + OvoB. Samples were stained for GFP (green) and ß-catenin (purple). The graph shows quantification of GFP-positive cells for each genotype. The Y axis is drawn using a log(10) scale.",
    "ncbi_link": "GFP: 
miR8: 12798320
mir8: 12798320
OvoB: 31429"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing Notch Intra Cellular Domain (NICD), and NICD + OvoB. In closeups (right), DAPI is shown in purple for improved contrast; the arrow highlights a cell with intermediate phenotype.",
    "ncbi_link": "GFP: 
NICD: 31293
Notch Intra Cellular Domain: 31293
OvoB: 31429"
  },
  {
    "caption": "esgtsF/O midguts expressing GFP alone (control), or expressing RasV12, and RasV12 + svb-RNAi (top panels). Bottom panels show esgts midguts expressing GFP alone (control), or expressing EGFR-DN, and EGFR-DN + OvoB. Samples were stained for GFP (green). The graph shows quantification of the number of GFP-positive cells in esgts midguts expressing GFP alone (ctrl), or expressing EGFR-DN, EGFR-DN + OvoB, and EGFR-DN + svb-RNAi. The Y axis is plotted as log(10).",
    "ncbi_link": "GFP: 
EGFR: 37455
OvoB: 31429
svb: 31429
Ras: 43873"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing ArmS10, ArmS10 + svb-RNAi, ArmS10 + OvoB ,TCF-DN, and TCF-DN + OvoB. Samples were stained for GFP (green). The graph shows quantification of the number of GFP-positive cells in esgts midguts expressing GFP alone (ctrl), or expressing TCF-DN, TCF-DN + OvoB, and TCF-DN + svb-RNAi. The Y axis is plotted as log(10).",
    "ncbi_link": "GFP: 
Arm: 31151
OvoB: 31429
svb: 31429
TCF: 43769"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing SvbREP. Samples were stained for GFP (green) and Prospero (red). Closeups correspond to boxed regions, with DAPI shown in purple and GFP-positive cells outlined in yellow.",
    "ncbi_link": "GFP: 
Svb: 31429"
  },
  {
    "caption": "esgts-F/O midguts expressing GFP alone (control), or expressing SvbREP. Samples were stained for GFP (green) and cleaved DCP1 (red). E' shows quantification of the number of GFP-positive cells in esgts guts expressing GFP alone (ctrl), or DIAP, SvbREP, and SvbREP + DIAP.",
    "ncbi_link": "GFP: 
DIAP: 39753
Svb: 31429"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing Notch-RNAi, Notch-RNAi + svb-RNAi, and Notch-RNAi + SvbREP. Samples were stained for GFP (green) and Prospero (red). The graph shows quantification of the number of GFP-positive cells.",
    "ncbi_link": "GFP: 
Notch: 31293
svb: 31429
Svb: 31429"
  },
  {
    "caption": "esgts midguts expressing GFP alone (control), or expressing STAT-RNAi, STAT-RNAi + svb-RNAi and STAT-RNAi + SvbREP. Samples were stained for GFP (green) and Prospero (red). The graph shows quantification of the number of GFP-positive cells.",
    "ncbi_link": "GFP: 
svb: 31429
Svb: 31429
STAT: 42428"
  },
  {
    "caption": "Cross sections of control MyoIAts midguts (expressing GFP and mCherry-RNAi), or expressing svb-RNAi, SvbACT, and Pri. Samples were stained for F-actin (white), GFP (green) and Tsp2a (yellow).",
    "ncbi_link": "mCherry: 
GFP: 
MyoIA: 43811
svb: 31429
Svb: 31429
Pri: 47191"
  },
  {
    "caption": "MyoIAts midguts expressing GFP alone (control), or expressing SvbACT. Samples were stained for GFP (green), Scribble (yellow), ß-catenin (purple) and DAPI (Blue). A' pictures display cross sections of the regions shown in A.",
    "ncbi_link": "GFP: 
Svb: 31429"
  },
  {
    "caption": "MyoIAts midguts expressing GFP alone (control), or expressing SvbACT. Samples were stained for GFP (green) and PH3 (red). The graph plots number of mitotic PH3-positive cells per midgut of MyoIAts guts expressing GFP alone (ctrl), or expressing SvbACT , and SvbREP + pri.",
    "ncbi_link": "GFP: 
Svb: 31429
pri: 47191"
  },
  {
    "caption": "Top: Immunoblot analysis of CIC in WT, Drosha_KO, Dicer_KO and Ago2&1_KO mESCs. TUBULIN was used as a loading control. Blot is a representative image of three biological replicates. Bottom: Bar graph showing quantification of CIC intensity, normalized to TUBULIN and relative to the WT sample in three biological replicates. Data information: Bar graph in Fig 2F shows mean intensity of CIC signal ± SD normalized to TUBULIN. Values are relative to WT, which was set to 1. P-values were calculated using a student's t-test comparing each value to the WT. *p-value<0.05.",
    "ncbi_link": "Ago2: 239528
Dicer: 192119
Drosha: 14000"
  },
  {
    "caption": "MA plot of the DGE analysis in miR-290-295_KO mESCs. Data information: In A, significant genes in MA plot were determined using an adjusted p-value of 0.1.",
    "ncbi_link": "miR-290: 102465789///100049710"
  },
  {
    "caption": "F, G. Integrated data for Tfap4 gene shows multiple lines of evidence for its regulation by miR-290-295. In addition to the data shown and described in Fig 1D, E, a second AGO2-binding dataset, based on cross-linking immunoprecipitation and sequencing (CLIP-seq), has been integrated. Response elements for miR-290-295 cluster members are denoted in red and labeled.",
    "ncbi_link": "miR-290: 102465789///100049710
Tfap4: 83383"
  },
  {
    "caption": "Top: Immunoblot analysis of TFAP4 in WT, Drosha_KO, Dicer_KO, Ago2&1_KO and miR-290-295_KO mESCs. LAMINB1 was used as a loading control. Blot is a representative image of three biological replicates. Bottom: Bar graph showing quantification of CIC intensity, normalized to LAMINB1 and relative to the WT sample in three biological replicates. Data information: In H bar graphs show mean intensity of TFAP4 signal ± SD normalized to LAMINB1 Values are relative to WT or the negative control mimic, which was set to 1. P-values were calculated using a student's t-test comparing each value to the WT. *p-value<0.05, **p-value<0.01, ****p-value<0.0001.",
    "ncbi_link": "Ago2: 239528
Dicer: 192119
Drosha: 14000
miR-290: 102465789///100049710"
  },
  {
    "caption": "Top: Immunoblot analysis of TFAP4 after transfection of miRNA mimics (miR-291a-5p, miR-291a-3p and miR-291a-5p+miR-291a-3p combined) in miR-290-295_KO mESCs. Immunoblots were stained with Coomassie blue dye as a loading control. Blot is a representative image of three biological replicates. Bottom: Bar graph showing quantification of TFAP4 intensity, normalized to Coomassie and relative to the WT sample in three biological replicates. Data information: In I, bar graphs show mean intensity of TFAP4 signal ± SD normalized to Coomassie. Values are relative to WT or the negative control mimic, which was set to 1. P-values were calculated using a student's t-test comparing each value to the WT. *p-value<0.05, **p-value<0.01, ****p-value<0.0001.",
    "ncbi_link": "miR-290: 102465789///100049710
miR-291a-3p: 100049715
miR-291a-5p: 100049715"
  },
  {
    "caption": "Top: Mature sequences of 5p and 3p miRNAs of the miR-290-295 family and the mature sequence of the human miR-302c-3p. Colors indicate identical seed sequences. Bottom: AGO2 CLIP-seq shows a peak at the miR-302c-3p binding site on human TFAP4.",
    "ncbi_link": "miR-302c-3p: 442895
TFAP4: 7023"
  },
  {
    "caption": "Immunoblot validation of siPOOL-mediated knock down of Tfap4. TFAP4 levels were compared between untreated WT versus miR-290-295_KO cells treated with a negative control and a Tfap4-targeted siPOOL. Immunoblots were stained with Coomassie blue dye as a loading control. Blot is a representative image of two biological replicates.",
    "ncbi_link": "miR-290: 102465789///100049710
Tfap4: 83383"
  },
  {
    "caption": "Scatterplot of DEG in miR-290-295_KO control versus siPOOL-Tfap4. SiPOOL experiments were performed in miR-290-295_KO cells and DE was assessed relative to a negative control siPOOL transfection. Only genes that are statistically significantly differentially expressed in miR-290-295_KO are shown. Genes predicted to be targeted by miR-290-295 are marked in blue. Genes are defined as rescued (orange) if the log2FoldChange-ratio between miR-290-295_KO control and siPOOL-Tfap4 is in the range [-2, -1/2]. Tfap4 is marked by a red dot.",
    "ncbi_link": "miR-290: 102465789///100049710
Tfap4: 83383"
  },
  {
    "caption": "Representative images of NANOG (red) and OCT4 (green) immunofluorescence staining in WT, Drosha_KO and Drosha & Tfap4_KO mESCs. Scale bar = 20 μm. Quantification of NANOG fluorescence signal intensity in WT, Drosha_KO and Drosha & Tfap4_KO mESCs show no significant rescue of NANOG intensity in Drosha & Tfap4_KO Data information: In E, box plots show nuclear intensity of NANOG in ~300 cells per genotype. P-values were generated using ordinary one-way ANOVA. ****p-value<0.0001. In panel E, the box plot's central band represents the median relative intensity for each genotype. The boxes represent the interquartile range and the whiskers represent the maximum and minimum relative intensity values. ",
    "ncbi_link": "Drosha: 14000
Tfap4: 83383"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) human DLD1 cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Human spheroids established from BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) DLD1 cells, were incubated with 1.25 µM olaparib or 0.5 µM chlorambucil over the indicated period of time.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA1-proficient (+BRCA1) or -deficient (-BRCA1) human RPE1-hTERT cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA1-proficient (+BRCA1) or -deficient (-BRCA1) TP53-deleted cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA1: 12189
TP53: 27223"
  },
  {
    "caption": "Dose-dependent viability assays of Brca1+/+ and Brca1-/- mouse mammary tumour-derived cell lines treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "Brca1: 12189"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA2-deficient (Capan-1) or -proficient (MIA PaCa-2) human pancreatic carcinoma-derived cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Dose-dependent viability assays of BRCA2-deficient (PEO1) or -proficient (C4-2) human ovarian tumour-derived cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "BRCA2-deficient (PEO1) or -proficient (C4-2) human ovarian tumour-derived cells were infected with lentiviruses expressing control or CHD4 shRNAs, followed by selection with puromycin for 72 hours. Dose-dependent viability assays were performed on cells treated with drugs at the indicated concentrations for six days.",
    "ncbi_link": "BRCA2: 675
CHD4: 1108"
  },
  {
    "caption": "BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) human DLD1 cells were incubated with 1 µM chlorambucil (Chl). Whole cell extracts prepared at the indicated time points during treatment were immunoblotted as shown. GAPDH was used as a loading control.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Quantification of chromosome aberrations and chromatid/chromosome break frequencies in BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) human DLD1 cells incubated with 1 μM chlorambucil or 1 µM cisplatin for 72 h. Data were obtained from three independent experiments and normalised to untreated controls. A minimum of 60 Giemsa-stained metaphases were analysed for each sample. Cis, cisplatin; Chl, chlorambucil.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Nude mice (nu/nu) were injected subcutaneously with 5 x 106 human DLD1 cells, BRCA2-proficient (A) or BRCA2-deficient (B). Tumour-bearing mice were treated with 3 mg/kg daily chlorambucil administered intraperitoneally (i.p.) for a total of ten days. Tumour weight was determined on the indicated days after initiation of the treatment.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "PDTCs derived from breast cancer samples as previously described (Bruna et al, 2016) were treated with chlorambucil at the indicated doses. Cell survival is represented relative to DMSO control. AB521, ER-negative tumour, no BRCA1 alteration; STG201, tumour with BRCA1 promoter methylation and loss of BRCA1 expression; VHIO179, tumour with BRCA1 germline mutation and MAD2L2 inactivating mutation (olaparib-resistant)",
    "ncbi_link": "BRCA1: 672
MAD2L2: 10459"
  },
  {
    "caption": "CB17/SCID mice were injected intramuscularly with 5 x 106 human BRCA2-deficient HCT116 cells. Tumour-bearing mice were treated on the indicated days with chlorambucil or cisplatin administered intraperitoneally (i.p.), or talazoparib administered orally (o.s.) Tumour volume was measured on the indicated days after treatment initiation and was expressed relative to tumour volume at the beginning of treatment (day 1). Scale bar, 40 µm. Each experimental group included n = 5 mice. Error bars represent SEM. Tumour sections were assessed at the end of each treatment using immunohistochemistry of γH2AX staining.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "HeLa cells were co-transfected with Myc empty vector (Myc), Myc-tagged FUNDC1 (F1-Myc) or Myc-tagged FUNDC1-ΔLIR mutant (ΔLIR-Myc) and Mito-OM-cherry, which localizes to the mitochondrial outer membrane, and immunostained with fluorescent anti-p62 and anti-Myc antibodies. Scale bar=10 μm.",
    "ncbi_link": "Mito-OM-cherry: 
F1: 139341
FUNDC1: 139341
Myc: 4609"
  },
  {
    "caption": "HeLa cells were co-transfected with Myc, F1-Myc or ΔLIR-Myc and Mito-OM-cherry and immunostained with anti-Ubiquitin (Ub) and anti-Myc antibodies. Scale bar=10 µm.",
    "ncbi_link": "Mito-OM-cherry: 
F1: 139341
Myc: 4609"
  },
  {
    "caption": "Fractionation analysis of HeLa cells transfected with Myc, F1-Myc or ΔLIR-Myc. The loading controls (L.C.) were α-Tubulin for total cell lysate (TCL) and cytosolic fraction (Cyto), and HSP60 for mitochondrial fraction (Mito).",
    "ncbi_link": "F1: 139341
Myc: 4609"
  },
  {
    "caption": "HeLa cells transfected with Myc or Myc/His6 double-tagged F1-Myc-His were lysed and precipitated with Ni-NTA beads. Samples were then subjected to SDS-PAGE. The differential band (upper arrow) was isolated and subjected to mass spectral analysis. The identified proteins with a score higher than 50 are listed.",
    "ncbi_link": "His: 
His6: 
F1: 139341
Myc: 4609"
  },
  {
    "caption": "Co-IP of endogenous HSC70 with F1-Myc or ΔLIR-Myc. α-Myc, anti-Myc antibody",
    "ncbi_link": "F1: 139341
Myc: 4609"
  },
  {
    "caption": "Co-IP analysis of endogenous FUNDC1 with Flag-HSP70 or Flag-HSC70. α-Flag, anti-Flag antibody. Flag，empty vector.",
    "ncbi_link": "Flag: 
HSP70: 3306
HSC70: 10963"
  },
  {
    "caption": "HeLa cells were co-transfected with Myc, F1-Myc or ΔLIR-Myc and Mito-OM-cherry and immunostained with anti-HSC70 and anti-Myc antibodies. Scale bar=10 µm.",
    "ncbi_link": "Mito-OM-cherry: 
F1: 139341
Myc: 4609"
  },
  {
    "caption": "Fractionation analysis of HeLa cells transfected with Myc or F1-Myc.",
    "ncbi_link": "F1: 139341
Myc: 4609"
  },
  {
    "caption": "HeLa cells were co-transfected with Ub-R-GFP and Myc or F1-Myc and immunostained with fluorescent anti-Myc and anti-GFP (α-GFP) antibodies. The α-GFP signals in F1-Myc transfected cells were lowered to avoid the overexposure of the mitochondrially localized R-GFP, making such signals of the equally distributed R-GFP invisible. Green arrowheads show the mitochondrially localized R-GFP proteins, which were more abundant than the equally distributed R-GFP and showed stronger R-GFP fluorescence, white arrowheads show the mitochondrially localized R-GFP proteins without stronger R-GFP fluorescence, although abundant. Scale bar=10 µm.",
    "ncbi_link": "R-GFP: 
F1: 139341
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells co-transfected with Ub-R-GFP and Myc or F1-Myc.",
    "ncbi_link": "R-GFP: 
F1: 139341
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "HeLa cells were co-transfected with Ub-R-GFP and F1-Myc. Mitochondria were isolated and then treated with or without proteinase K (Pro.K), or proteinase K in combination with digitonin or Triton X-100 (TX-100). Samples were then subjected to Immunoblot analysis. HSP60, TIM23 and TOM20 are representatives of mitochondrial matrix-, mitochondrial inner membrane- and mitochondrial outer membrane-localized proteins, respectively.",
    "ncbi_link": "R-GFP: 
F1: 139341
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells stably transfected with control (Ctrl) shRNA vector or HSC70 shRNA and transiently co-transfected with Ub-R-GFP, Flag or Flag-HSC70 (shRNA-resistant) and Myc, or F1-Myc, as indicated.",
    "ncbi_link": "Flag: 
R-GFP: 
F1: 139341
Myc: 4609
HSC70: 10963
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of the HeLa cells transfected with Ub-R-GFP and treated with DMSO (control vehicle) or 10 μM MG132 for 4 hours.",
    "ncbi_link": "R-GFP: 
Ub: 7316///7314"
  },
  {
    "caption": "Proteinase K protection analysis of the mitochondria isolated from the HeLa cells transfected with Ub-R-GFP and treated with MG132.",
    "ncbi_link": "R-GFP: 
Ub: 7316///7314"
  },
  {
    "caption": "Proteinase K protection analysis of the mitochondria isolated from HeLa cells co-transfected with Ub-R-GFP and Ctrl, TOM20, TOM22 or TOM70 shRNA and treated with MG132.",
    "ncbi_link": "R-GFP: 
TOM20: 9804
TOM22: 56993
TOM70: 9868
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells stably transfected with Ctrl or LONP1 shRNA and transiently co-transfected with Ub-R-GFP and Myc or LONP1 (shRNA-resistant) and then treated with DMSO or MG132.",
    "ncbi_link": "R-GFP: 
LONP1: 9361
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells stably transfected with Ctrl shRNA, F1 shRNA, or F1 shRNA together with shRNA-resistant F1-Myc or ΔLIR-Myc, and transiently transfected with Ub-R-GFP and then treated with DMSO or MG132.",
    "ncbi_link": "R-GFP: 
F1: 139341
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells stably transfected with Ctrl or HSC70 shRNA and transiently co-transfected with Ub-R-GFP and Flag or shRNA-resistant Flag-HSC70 and then treated with DMSO or MG132.",
    "ncbi_link": "Flag: 
R-GFP: 
HSC70: 10963
Ub: 7316///7314"
  },
  {
    "caption": "Fractionation analysis of HeLa cells stably transfected with Ctrl or HSP70 shRNA and transiently co-transfected with Ub-R-GFP and Flag or shRNA-resistant Flag-HSP70 and then treated with DMSO or MG132.",
    "ncbi_link": "Flag: 
R-GFP: 
HSP70: 3306
Ub: 7316///7314"
  },
  {
    "caption": "Mitochondria were isolated from the untransfected cells, cytosols were isolated from the cells transfected with GFP or Ub-R-GFP and treated with DMSO or MG132 for 8 hours, the isolated mitochondria and cytosols were then subjected to in vitro protein import analysis.",
    "ncbi_link": "GFP: 
R-GFP: 
Ub: 7316///7314"
  },
  {
    "caption": "Mitochondria isolated from the untransfected cells were resuspended in the cytosol isolated from the cells transfected with Ub-R-GFP and incubated at RT for I hour, the mitochondria were then isolated from the in vitro system, then treated with or without proteinase K and subjected to immunoblot analysis.",
    "ncbi_link": "R-GFP: 
Ub: 7316///7314"
  },
  {
    "caption": "Mitochondria were isolated from the cells transfected with ctrl shRNA, F1 shRNA or F1 shRNA together with F1-Myc, cytosols were isolated from the cells transfected with Ub-R-GFP, the isolated mitochondria and cytosols were then subjected to in vitro protein import analysis.",
    "ncbi_link": "R-GFP: 
F1: 139341
Myc: 4609
Ub: 7316///7314"
  },
  {
    "caption": "Cytosol isolated from the cells transfected with Ub-R-GFP were mixed with the cytosols isolated from the cells transfected with ctrl shRNA, HSC70 shRNA or HSC70 shRNA together with Flag-HSC70, mitochondria were isolated from the untransfected cells, the isolated mitochondria and cytosol mixtures were then subjected to in vitro protein import analysis.",
    "ncbi_link": "Flag: 
R-GFP: 
HSC70: 10963
Ub: 7316///7314"
  },
  {
    "caption": "Immunoblot analysis of the HeLa cells transfected with or without HA-Bcl-xL and treated with DMSO or MG132 for 6 hours.",
    "ncbi_link": "HA: 
Bcl-xL: 572"
  },
  {
    "caption": "Ni2+-NTA precipitation of HeLa cells transfected with indicated vectors. S13A-Myc-His, Myc/His6 double-tagged FUNDC1-S13A mutant.",
    "ncbi_link": "His: 
His6: 
FUNDC1: 139341
Myc: 4609"
  },
  {
    "caption": "HeLa cells were transfected with GFP-p62, treated with DMSO or 10 μM MG132 for 8 hours and then immunostained with anti-Ub and anti-γ-Tubulin antibodies. Note that the aggresome (blue arrowhead), rather than the MAPAs (white arrowheads), colocalizes with γ-Tubulin. Scale bar=10 µm.",
    "ncbi_link": "GFP: 
p62: 8878"
  },
  {
    "caption": "D, E. HeLa cells were transfected with Ctrl, TOM20, TOM22 or TOM70 shRNA vectors including nuclear localized GFP (N-GFP) expressing elements, then treated with MG132 and immunostained with the indicated antibodies. Scale bar=10 µm. Quantification is show in (E).",
    "ncbi_link": "GFP: 
TOM20: 9804
TOM22: 56993
TOM70: 9868"
  },
  {
    "caption": "F, G. HeLa cells were transfected with GFP or GFP-Bcl-xL, then treated with MG132 and immunostained with anti-p62 antibodies. Scale bar=10 µm. Quantification is show in (G).",
    "ncbi_link": "GFP: 
Bcl-xL: 572"
  },
  {
    "caption": "H, I. HeLa cells were stably transfected with Ctrl or LONP1 shRNA, treated with MG132 and immunostained with the indicated antibodies. Scale bar=10 µm. Quantification is show in (I).",
    "ncbi_link": "LONP1: 9361"
  },
  {
    "caption": "csCLEM analysis of cells transfected with GFP-p62 and treated with MG132. Red arrowheads show the dark red fluorescent beads used to correlate the images from light microscopy (LM) and transmission electron microscopy (TEM). The blue arrowhead shows a MAPA observed under LM and TEM.",
    "ncbi_link": "GFP: 
p62: 8878"
  },
  {
    "caption": "Immunoblot analysis of the TX-100-soluble and -insoluble fractions of HeLa cells transfected with Ub-R-GFP and treated with MG132 as indicated.",
    "ncbi_link": "R-GFP: 
Ub: 7316///7314"
  },
  {
    "caption": "HeLa cells were co-transfected with Mito-OM-cherry and Mito-MTX-GFP, then treated with DMSO or MG132 and immunostained with anti-p62 antibody. Note the colocalization of a p62 punctum with a structure that is positive for Mito-OM-cherry but not for Mito-MTX-GFP (white arrowheads) in MG132-treated cells. Scale bar=10 µm.",
    "ncbi_link": "Mito-MTX-GFP: 
Mito-OM-cherry: "
  },
  {
    "caption": "HeLa cells were transfected with Mito-MTX-GFP, then treated with DMSO or MG132 and immunostained with anti-p62 and anti-TIM23 antibodies. Note the colocalization of a p62 punctum with a structure that is positive for TIM3 but not for Mito-MTX-GFP (white arrowhead) in MG132-treated cells. Scale bar=10 µm.",
    "ncbi_link": "Mito-MTX-GFP: "
  },
  {
    "caption": "HeLa cells were co-transfected with Mito-MTX-GFP and OTC-Myc or OTC-Δ-Myc, treated with DMSO or MG132 and immunostained with anti-Myc and anti-p62 antibodies. Note that the p62-labled MAPAs were colocalized with OTC-∆ (red arrowheads), but not with OTC (white arrowheads) in the MG132 treated cells. Scale bar=10 µm.",
    "ncbi_link": "Mito-MTX-GFP: 
Myc: 4609
OTC: 5009"
  },
  {
    "caption": "Time-lapse analysis of live HeLa cells transfected with OTC-Δ-GFP and Mito-MTX-DsRed and treated with MG132. White arrowheads show a OTC-Δ-GFP-positive Mito-MTX-DsRed-negative structure that eventually segregated from the mitochondrial network.",
    "ncbi_link": "GFP: 
Mito-MTX-DsRed: 
OTC: "
  },
  {
    "caption": "Immunoblot analysis of the MG132-induced deposition of FUNDC1, TIM23 and p62 in HeLa cells transfected with Ctrl or DLP1 shRNA.",
    "ncbi_link": "DLP1: 10059"
  },
  {
    "caption": "C, D. Immunoblot analysis of the MG132-induced deposition of FUNDC1 in cells transfected with ctrl shRNA, FIS1 shRNA or FIS1 shRNA together with shRNA-resistant Flag-FIS1. Quantification is shown in (D).",
    "ncbi_link": "Flag: 
FIS1: 51024"
  },
  {
    "caption": "E, F. HeLa cells were stably transfected with Ctrl or FIS1 shRNA, treated with MG132 and immunostained with indicated antibodies. Scale bar=10 µm. Quantification is shown in (F).",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "G, H. Fractionation analysis of HeLa cells stably transfected with Ctrl or FIS1 shRNA, then transiently co-transfected with Ub-R-GFP and Flag or Flag-FIS1 and treated with DMSO or MG132. Quantification is shown in (H).",
    "ncbi_link": "Flag: 
R-GFP: 
FIS1: 51024
Ub: 7316///7314"
  },
  {
    "caption": "HeLa cells were transfected with GFP-LC3, treated with DMSO or 10 μM MG132 for 8 hours and immunostained with anti-p62 antibody. Scale bar=10 µm.",
    "ncbi_link": "GFP: 
LC3: 440738///81631///84557"
  },
  {
    "caption": "Immunoblot analysis of the TCL of HeLa cells stably transfected with Ctrl or ATG5 shRNA and treated with MG132 as indicated.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "HeLa cells were stably transfected with the indicated vectors, transiently transfected with GFP-LC3, then treated with 10 μM MG132 for 8 hours and immunostained with anti-p62 antibody. Scale bar=10 µm.",
    "ncbi_link": "GFP: 
LC3: 440738///81631///84557"
  },
  {
    "caption": "TEM analysis of F1 shRNA/F1-Myc or F1 shRNA/ΔLIR-Myc cells treated with MG132 for 8 hours. Yellow arrowheads show the MAPAs. Blue arrows show the places where membrane is absent. White arrowheads show the layered aggregates budding from mitochondria. Scale bar=500 nm; M, mitochondrion.",
    "ncbi_link": "F1: 139341
Myc: 4609"
  },
  {
    "caption": "Quantification of SA-β-gal staining of HeLa cells stably transfected with the indicated vectors, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. The up-regulation of p53 and p21 at 3 days after pulse treatment with MG132 was alleviated by FUNDC1 knockdown and restored by reintroduction of F1-Myc or ΔLIR-Myc, although the basal level of p53 in FUNDC1 knockdown cells is higher than that in control cells.",
    "ncbi_link": "F1: 139341
FUNDC1: 139341
Myc: 4609"
  },
  {
    "caption": "H. HeLa cells stably transfected with the indicated vectors, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. Immunoblot analysis of the cells is shown in (H). The up-regulation of p53 and p21 at 3 days after pulse treatment with MG132 was alleviated by FUNDC1 knockdown and restored by reintroduction of F1-Myc or ΔLIR-Myc, although the basal level of p53 in FUNDC1 knockdown cells is higher than that in control cells.",
    "ncbi_link": "F1: 139341
FUNDC1: 139341
Myc: 4609"
  },
  {
    "caption": "Quantification of MG132-induced SA-β-gal staining in HeLa cells stably transfected with Ctrl, HSP70 or HSC70 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. The up-regulation of p53 and p21 at 3 days after pulse treatment with MG132 was alleviated by HSC70 knockdown, although the basal level of p53 in HSC70 knockdown cells is higher than that in control cells. Both p53 and p21 were up-regulated in HSP70 knockdown cells treated with or without MG132.",
    "ncbi_link": "HSP70: 3306
HSC70: 10963"
  },
  {
    "caption": "J. HeLa cells stably transfected with Ctrl, HSP70 or HSC70 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. Immunoblot analysis of the cells is shown in (J). The up-regulation of p53 and p21 at 3 days after pulse treatment with MG132 was alleviated by HSC70 knockdown, although the basal level of p53 in HSC70 knockdown cells is higher than that in control cells. Both p53 and p21 were up-regulated in HSP70 knockdown cells treated with or without MG132.",
    "ncbi_link": "HSP70: 3306
HSC70: 10963"
  },
  {
    "caption": "HeLa cells stably transfected with tetracycline (Tet)-inducible Bcl-xL expression vector were incubated in DMEM containing Tet or not for 12 hours, then treated with DMSO or 10 μM MG132 for 8 hours, then washed and incubated in fresh medium for another 3 days, Cells were then subjected to SA-β-gal staining. The induced Bcl-xL was detectable even 3 days after treatment withdrawal, because this protein is stable.",
    "ncbi_link": "Bcl-xL: 572"
  },
  {
    "caption": "L. HeLa cells stably transfected with tetracycline (Tet)-inducible Bcl-xL expression vector were incubated in DMEM containing Tet or not for 12 hours, then treated with DMSO or 10 μM MG132 for 8 hours, then washed and incubated in fresh medium for another 3 days, Immunoblot analysis of the cells is shown in (L). The induced Bcl-xL was detectable even 3 days after treatment withdrawal, because this protein is stable.",
    "ncbi_link": "Bcl-xL: 572"
  },
  {
    "caption": "Quantification of the SA-β-gal staining of HeLa cells stably transfected with Ctrl or LONP1 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days.",
    "ncbi_link": "LONP1: 9361"
  },
  {
    "caption": ", N. HeLa cells stably transfected with Ctrl or LONP1 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. Immunoblot analysis of the cells is shown in (N).",
    "ncbi_link": "LONP1: 9361"
  },
  {
    "caption": "Quantification of the SA-β-gal staining of HeLa cells stably transfected with Ctrl or FIS1 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days.",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "P. HeLa cells stably transfected with Ctrl or FIS1 shRNA, treated with DMSO or MG132 for 8 hours, then washed and cultured for 3 days. Immunoblot analysis of the cells is shown in (P).",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "(A to D) 10- to 11-week-old mice were treated with vehicle control or AT845 at the vector doses indicated and followed for 12 weeks (N = 7 or 8 per cohort). (A) Vector copy number, (B) GAA levels, (C) GAA activity, and (D) glycogen content in cardiac and skeletal muscles. (C to D) Statistical analysis: two-way ANOVA, Dunnett's test. Data are presented as box-and-whisker plots with Tukey whiskers that show minimum, median, and maximum. Asterisks (*) indicate significant differences compared with untreated Gaa-/- mice (black) or wild-type mice (red). *, P<0.05; **, P<0.01; ***, P<0.001; ****, P <0.0001. See also Appendix Table S1.",
    "ncbi_link": "Gaa: 14387"
  },
  {
    "caption": "Representative images of H&E (top) and PAS (bottom) staining of the quadriceps in wild-type and Gaa-/- mice untreated or treated with escalating doses of AT845 (3×1013, 1×1014, and 3×1014 vg/kg). Scale bar, 80 µm. (See also Appendix Table S1)",
    "ncbi_link": "Gaa: 14387"
  },
  {
    "caption": "A-D (A, B) Body weight curves and (C, D) grip response - ability to grip onto an inverted wire screen for a 60-second period - in wild-type and Gaa-/- mice untreated or treated with escalating doses of AT845 (3×1013, 1×1014, and 3×1014 vg/kg). All groups had n=9 at all timepoints, except the 6 week timepoint (females) and the 12 week timepoint (males and females) for the Gaa-/- mice, which had n=8 per group. Female mice dosed with 3×1013, 1×1014, and 3×1014 vg/kg had a 22%, 11%, and 0% failure rate at week 12, respectively; in comparison, the female control WT mice had a 22% failure rate and the control Gaa-/- mice had a 38% failure. Male mice dosed with 3×1013, 1×1014, and 3×1014 vg/kg had a 56%, 33%, and 11% failure rate at week 12, respectively; in comparison, the male control WT mice had a 11% failure rate and the control Gaa-/- mice had a 100% failure. Bars represent median. Data show a dose-dependent improvement in grip response following treatment with AT845. Statistical analysis: two-way ANOVA, Dunnett's test. Asterisks (*) indicate significant differences compared with untreated Gaa-/- mice at each respective time point. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.",
    "ncbi_link": "Gaa: 14387"
  },
  {
    "caption": "A Western blot analysis STAT expression and phosphorylation. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F/+ (WT/YF) or Stat1-/- (S1) mice were treated with 250 IU/mL of IFNβ or 5 ng/mL of IFNγ for 0.5, 6, 12 and 24 h. Whole cell extracts were collected and tested in western blot for levels of phosphorylation of STAT1 (Y701) and STAT2 (Y689) and total level of STAT1 and STAT2. The blots are representative of more than 3 independent experiments.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "B Effect of STAT1Y701Fheterozygosity on the expression of type I IFN-induced genes (ISG). BMDMs of wild type (WT), Stat1Y701F/+ (WT/YF) or Stat1-/- (S1) mice were treated with 250 IU/mL of IFNβ for 4 and 48 h. Gene expression was measured by Q-PCR and normalized to Gapdh and to the expression levels in untreated wild type cells. The bars represent mean values with the standard deviations (SD) of three independent experiments.C Effect of STAT1Y701Fheterozygosity on the expression of IFNγ-induced genes. BMDMs of wild type (WT), Stat1Y701F/+ (WT/YF) or Stat1-/- (S1) mice were treated with 5 ng/mL of IFNγ for 4 and 48 h. Gene expression was measured by Q-PCR and normalized to Gapdh and to the expression levels in untreated wild type cells. The bars represent mean values with the standard deviations (SD) of three independent experiments.",
    "ncbi_link": "Gapdh: 
Stat1: 20846
STAT1: 20846"
  },
  {
    "caption": "A Effect of STAT1Y701F homozygosity on STAT1 expression in mouse cells and organs. Spleens, livers or bone marrow derived macrophages (BMDMs) were isolated from wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice. Whole cell extracts were collected and tested for levels of total Stat1 in western blot. The blots are representative of more than 3 independent experiments.",
    "ncbi_link": "STAT1: 20846
Stat1: 20846"
  },
  {
    "caption": "B Effect of STAT1Y701F homozygosity on STAT1 phosphorylation at Y701. BMDMs were isolated from wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice and stimulated for 30 min with 250 IU/mL of IFNβ or 5 ng/mL of IFNγ. Whole cell extracts were collected and tested for levels of STAT1 phosphorylation on Y701 in western blot. The blots are representative of more than 3 independent experiments.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "C Effect of STAT1Y701Fhomozygosity on the expression of IFNβ-induced genes. BMDMs of wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice were treated with 5 ng/mL of IFNγ for 4 or 48 h. Gene expression was measured by Q-PCR and normalized to Gapdh and to the expression levels in untreated wild type cells. Bars represent a mean value of 3 independent experiments. Error bars represent standard error of the mean (SEM); asterisks denote the level of statistical significance (ns, p>0.05); the p-values were calculated using paired ratio t-test.",
    "ncbi_link": "Gapdh: 
Stat1: 20846"
  },
  {
    "caption": "D Effect of STAT1Y701Fhomozygosity on the expression of type I IFN-induced genes (ISG). BMDMs were isolated from wild type (WT), Stat1Y701F, Stat1-/-, Stat2-/- and IRF9-/- mice treated with 250 IU/mL of IFNβ for 4, 8, 12, 24 or 48 h. Gene expression was measured by Q-PCR and normalized to Gapdh and to the expression levels in untreated wild type cells. Bars represent a mean value of 3 independent experiments. Error bars represent standard error of the mean (SEM); asterisks denote the level of statistical significance (ns, p>0.05; *, p≤ 0.05; **, p≤ 0.01); the p-values were calculated using paired ratio t-test.",
    "ncbi_link": "Gapdh: 
IRF9: 16391
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "E STAT1 and STAT2 phosphorylation in Stat1-/-, Stat1Y701F, Stat2-/- and Irf9-/- macrophages. BMDMs were isolated from wild type (WT), Stat1Y701F (YF), Stat1-/- (S1), Stat2-/- (S2) and IRF9-/- (IRF9) mice and treated with 250 IU/mL of IFNβ for 30 min or 6, 12 or 24 h. The whole cell extracts were collected and tested in western blot for levels of phosphorylation of STAT1 on Y701 and of STAT2 on Y689. The same cell extracts were tested for total levels of STAT1 and STAT2. The blots are representative of more than 3 independent experiments.",
    "ncbi_link": "IRF9: 16391
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "A IFNβ-stimulated binding of STAT2 to ISRE sequences of Mx2 and IRF7 promoters. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F (YF), Stat1-/- (S1), Stat2-/- (S2) and IRF9-/- (IRF9) mice were treated with 250 IU/mL of IFNβ for 2 or 24 h. Cells were crosslinked, sonicated and immunoprecipitated with STAT2-specific antibody. The amount of precipitated DNA was measured by Q-PCR. Bars represent a mean value of 3 independent experiments. Error bars represent standard error of the mean (SEM); asterisks denote the level of statistical significance (**, p≤ 0.01); the p-values were calculated using paired ratio t-test.",
    "ncbi_link": "IRF7: 54123
IRF9: 16391
Mx2: 17858
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "B Impact of STAT2 deficiency on IFNβ -stimulated STAT1 association with the Mx2 ISRE. BMDMs of wild type (WT), Stat1-/- (S1) and Stat2-/- (S2) mice were treated with 250 IU/mL of IFNβ for 2 or 24 h. Cells were crosslinked, sonicated and immunoprecipitated with STAT1-specific antibody. The amount of precipitated DNA was measured by Q-PCR. Bars represent mean values of three independent experiments; error bars represent standard error of mean (SEM).",
    "ncbi_link": "Mx2: 17858
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "C Simultaneous association of STAT1 and STAT2 with the Mx2 ISRE analyzed by ChIP-reChIP. BMDMs of wild type (WT) mice were treated with 250 IU/mL of IFNβ for 2 or 24 h. Cells were crosslinked, sonicated and immunoprecipitated with either STAT1-specific antibody and re-immunoprecipitated with STAT2-specific antibody or vice versa. The amount of precipitated DNA was measured by Q-PCR. Bars represent mean values of three independent experiments; error bars represent standard deviation (SD).",
    "ncbi_link": "Mx2: 17858"
  },
  {
    "caption": "D Impact of STAT1Y701F on delayed, STAT2-mediated expression of IFN-induced genes. Stat1-/- fibroblasts were transfected with plasmids driving expression of the indicated proteins. 24 h after transfection, 250 IU/ml of IFNβ was added to the transfected cells and ISG expression was determined by Q-PCR after 48h of cytokine treatment. Gene expression was measured by Q-PCR and normalized to Gapdh. Bars represent a mean value of 3 independent experiments. Error bars represent standard error of the mean (SEM) and asterisks denote the level of statistical significance (*, p≤ 0.05); the p-values were calculated using paired ratio t-test.",
    "ncbi_link": "Gapdh: 
STAT1: 20846
Stat1: 20846
STAT2: 20847"
  },
  {
    "caption": "A Analysis of STAT2 nuclear translocation by immunofluorescence. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F (YF), Stat1-/- (S1), Stat2-/- (S2) and IRF9-/- (IRF9) mice were seeded on cover slips and stimulated with 250 IU/mL of IFNβ for 30 min or 24 h. The cells were fixed and stained for STAT2 specific antibody followed by Alexafluor® 488 conjugated secondary antibody (green). Nuclei were stained with DAPI (blue). Studies are representative of more than three independent experiments. The scale bars represent 10 µm.B Quantitative evaluation of STAT2nuclear translocation. The intensity of STAT2-dependent immunofluorescence over DNA staining (DAPI) was quantified using ImageJ software in 20 cells from two independent experiments. Bars represent a mean with standard deviation (SD) and asterisks denote the level of statistical significance (***, p≤ 0.001); p-value was calculated using unpaired t-test.",
    "ncbi_link": "IRF9: 16391
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "A Legionella pneumophila growth in unstimulated macrophages. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F, Stat1-/- mice were seeded on in the 24-well plates and infected with L. pneumophila (JR32 Fla-, MOI 0.25). The numbers of colony forming units (CFUs) were determined 24 h, 48 h and 72 h after infection on charcoal yeast extract plates (CYE). The 0 time point was collected 1.5 h after the infection.B Legionella pneumophila growth in IFNβ-treated macrophages. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F, Stat1-/- mice were seeded in 24-well plates, treated with 500 U/mL of IFNβ and then infected with L. pneumophila (JR32 Fla-, MOI 0.25). The numbers of colony forming units (CFUs) were determined 24 h, 48 h and 72 h after infection on charcoal yeast extract plates (CYE). The 0 time point was collected 1.5 h after the infection.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "A Western blot analysis of STAT1 tyrosine phosphorylation. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice were infected with L. monocytogenes (LO28, MOI 10) for 5 or 6 h. Whole cell extracts were collected and tested in western blot for levels of total STAT1 and phosphorylation of STAT1 on tyrosine (Y701). The blots are representative of more than 3 independent experiments.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "B Impact of Stat1Y701F mutation, or of deletion of ISGF3 subunits on the expression of the IFNβ gene. BMDMs of wild type (WT), Stat1Y701F, Stat1-/-, Stat2-/- and IRF9-/- mice were infected with L. monocytogenes (LO28, MOI 10) for 4, 8, 12, 24 or 48 h. Levels of Ifnβ gene expression were determined by Q-PCR. Bars represent mean values of three independent experiments. Error bars represent standard error of mean (SEM).",
    "ncbi_link": "Ifnβ: 15977
IFNβ: 15977
IRF9: 16391
Stat1: 20846
Stat2: 20847"
  },
  {
    "caption": "A Impact of Stat1 deficiency or of STAT1Y701F mutation on the growth of Listeria monocytogenes in macrophages. Bone marrow derived macrophages (BMDMs) of wild type (WT), Stat1Y701F and Stat1-/- mice were infected with L. monocytogenes (LO28, MOI 10). Colony forming unit (CFU) numbers were determined 1, 2, 4, 6 or 8 h after infection by plating on brain-heart-infusion (BHI) agar plates. The graph represents biological triplicates and the data are represented as mean values. Error bars represent standard deviation (SD) and asterisks denote statistically significant differences (ns, p>0.05; **, p≤0.01; ***, p≤ 0.001); p-values were calculated using unpaired t-test.",
    "ncbi_link": "STAT1: 20846
Stat1: 20846"
  },
  {
    "caption": "B Survival of mice infected with L. monocytogenes. 10 wild type (WT), Stat1Y701F and Stat1-/- mice per group were infected by intraperitoneal injection of 1x 102 viable L. monocytogenes. Survival was monitored over 10 days. The study is representative of more than 3 independent experiments.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "C Organ pathogen burdens of mice infected with L. monocytogenes. Wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice were infected by intraperitoneal injection of 1x 102 viable L. monocytogenes. Number of colony forming units (CFU) in organs was determined at 48 h, 72 h or at the terminal stage of infection by plating homogenates on brain-heart-infusion (BHI) agar plates or Oxford agar plates (for lungs). Dots represent pooled data of 3 independent experiments. Lines represent the median and asterisks denote statistically significant differences (ns, p>0.05; *, p≤ 0.05; **, p≤ 0.01; ***, p≤ 0.001; ****, p≤ 0.0001); p-values were calculated using Mann-Whitney test.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "A Immunohistochemical analysis of infection and inflammatory infiltrates. Wild type (WT), Stat1Y701F and Stat1-/- mice were infected by intraperitoneal injection of 1x102 viable L. monocytogenes for 48 h. Liver sections were examined by immunohistochemistry with L. monocytogenes or Ly6C/Ly6G specific antibody. The scale bars on 20x magnification images represent 100 µm and 50 µm on the 63x magnification images.B Quantitative evaluation of inflammatory infiltrates. Infiltrates representing the entire surface of sections from five animals per genotype were counted and categorized according to their size.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "C Liver pathology in infected mice. Wild type (WT), Stat1Y701F (YF) and Stat1-/- (S1) mice were infected by intraperitoneal injection of 1x105 viable L. monocytogenes for 72 h. Serum was collected and tested for ALT activity. Lines represent the median and asterisks denote statistically significant differences (*, p≤ 0.05; ***, p≤ 0.001); p-values were calculated using unpaired t-test.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "(A) The aerial part of M. truncatula upon infection with S. meliloti ∆argI1, ∆argI2, ∆argI1,2 and the dicarboxylate transport mutant ∆dctAB were smaller than those inoculated with the wild type strain, highlighting the importance of arginine catabolism for nitrogen fixation",
    "ncbi_link": "argI1: 
argI2: 
dctAB: "
  },
  {
    "caption": "(B) Cross sections of nodules bearing S. meliloti WT or arginine catabolism mutant ∆argI1, ∆argI2 reveals the yellowish color of non-functional nodules induced by the ∆argI1 ∆argI2 double deletion mutant.",
    "ncbi_link": "argI1: 
argI2: "
  },
  {
    "caption": "(C) Bacteroid ultrastructure across nodule sections determined by scanning electron microscopy indicates the presence of hollow nodules with aberrant cell morphology in the ∆argI1 ∆argI2 double deletion mutant defective in arginine catabolism.",
    "ncbi_link": "argI1: 
argI2: "
  },
  {
    "caption": "H. ST2 wild type, TBK1 KO, IKKε KO, or cells lacking both kinases (DKO) were stimulated with IL-17 (500 ng/ml) as indicated and analyzed by immunoblotting.",
    "ncbi_link": "IKKε: 56489
TBK1: 56480"
  },
  {
    "caption": "I. TBK1/IKKε DKO cells reconstituted with either wild type or kinase dead mutant (K38A) version of both kinases were stimulated with IL-17 (500 ng/ml) as indicated and analyzed by immunoblotting.",
    "ncbi_link": "IKKε: 56489
TBK1: 56480"
  },
  {
    "caption": "ST2 wild type or TBK1/IKKε DKO cells were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. (A) The heatmap shows the row-normalized Z-Score calculated from log2 transformed iBAQ intensities from five independent experiments.",
    "ncbi_link": "IKKε: 56489
TBK1: 56480"
  },
  {
    "caption": "ST2 wild type or TBK1/IKKε DKO cells were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. (B) The ratio between iBAQ intensities of selected IL-17RSC components to iBAQ intensity of IL-17RC. Mean + SEM from five independent experiments is shown, statistical significance was determined by two‐tailed Mann-Whitney test.",
    "ncbi_link": "IKKε: 56489
TBK1: 56480"
  },
  {
    "caption": "C. ST2 wild type or TBK1/IKKε DKO cells were stimulated with SF-IL-17 (500 ng/ml) for 15 minutes or were left unstimulated and IL-17 was added post lysis. Lysates were subjected to anti-Flag immunoprecipitation to isolate IL-17RSC and samples were analyzed by immunoblotting. ACT1 phosphorylation detected as upper band in WT cells is absent in TBK1/IKKε DKO cells.",
    "ncbi_link": "IKKε: 56489
TBK1: 56480"
  },
  {
    "caption": "E. ST2 wild type or HOIP-deficient cells were pretreated with TBK1/IKKε inhibitor MRT67307 (2 µM), stimulated with IL-17 (500 ng/ml) as indicated, solubilized, and analyzed by immunoblotting. * indicates unspecific band.",
    "ncbi_link": "HOIP: 268749"
  },
  {
    "caption": "A. ST2 wild type and ACT1-deficient cells were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. As a control, cells were first solubilized and SF-IL-17 was added only post lysis. Number of identified peptides (unique + razor) and iBAQ intensities for each protein in two independent experiments are shown.",
    "ncbi_link": "ACT1: 109776"
  },
  {
    "caption": "B. ST2 wild type, ACT1 KO or TRAF6 KO cells were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. Lysates were subjected to anti-Flag immunoprecipitation to isolate IL-17RSC and samples were analyzed by immunoblotting.",
    "ncbi_link": "ACT1: 109776
TRAF6: 22034"
  },
  {
    "caption": "C. ST2 cells deficient in TRAF6 reconstituted with TRAF6(WT) or enzymatically inactive TRAF6(C70A) were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. Number of identified peptides (unique + razor) and iBAQ intensities for each protein in two independent experiments are shown.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "D. TRAF6 deficient cells reconstituted with TRAF6(WT), TRAF6(C70A) or empty vector were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. IL-17RSC was isolated from lysates by anti-Flag immunoprecipitation and analyzed by immunoblotting. Short and long exposure of the same membrane stained for Act1 are shown for lysate and IP samples, respectively.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "TRAF6 deficient cells reconstituted with the indicated constructs were pretreated or not with TBK1/IKKε inhibitor MRT67307 (2 µM) and stimulated with IL-17 (500 ng/ml) for indicated time. (E) The activation of signaling pathways analyzed by immunoblotting.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "TRAF6 deficient cells reconstituted with the indicated constructs were pretreated or not with TBK1/IKKε inhibitor MRT67307 (2 µM) and stimulated with IL-17 (500 ng/ml) for indicated time. The induction of mRNA for selected genes analyzed by real time PCR. Mean + SEM from four independent experiments is shown, statistical significance was determined using unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "G. ST2 cells wild type or NEMO KO were stimulated with IL-17 (500 ng/ml) for indicated time points, solubilized and analyzed by immunoblotting.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. Lysates were subjected to anti-Flag immunoprecipitation to isolate IL-17RSC. Samples were analyzed by immunoblotting (H).",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated with SF-IL-17 or were left unstimulated and IL-17 was added post lysis. results from four independent experiments were quantified by densitometry and mean + SEM from four independent experiments is shown (I).",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. (A) The heatmap shows the row-normalized Z-Score calculated from log2 transformed iBAQ values from two independent experiments.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated for 15 minutes with SF-IL-17 (500 ng/ml), solubilized and IL-17RSC was isolated via consecutive Flag and Strep immunoprecipitation and analyzed by MS. (B) The ratio between iBAQ intensities of selected IL-17RSC components to iBAQ intensity of IL-17RC. Mean + SEM from two independent experiments is shown.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. Lysates were subjected to anti-Flag immunoprecipitation to isolate IL-17RSC (C) and analyzed by immunoblotting.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ST2 wild type or NEMO KO cells were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. Lysates were tested for activation of signaling pathways (D) and analyzed by immunoblotting.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "F. ST2 wild type or NEMO KO cells were stimulated with TNF (50 ng/ml) for indicated time points and lysates were analyzed by immunoblotting.",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "ACT1 KO cells were reconstituted with either wild type ACT1 or indicated mutants or ACT1 with all nine identified phospho-sites mutated to alanines (9ST mut). Cells were stimulated with IL-17 (500 ng/ml) as indicated and lysates were analyzed by immunoblotting. * indicates nonspecific band.",
    "ncbi_link": "ACT1: 109776"
  },
  {
    "caption": "ACT1 KO cells were reconstituted with either wild type ACT1 or indicated mutants or ACT1 with all nine identified phospho-sites mutated to alanines (9ST mut). Cells were stimulated with IL-17 (500 ng/ml) as indicated and lysates were analyzed by immunoblotting. * indicates nonspecific band.",
    "ncbi_link": "ACT1: 109776"
  },
  {
    "caption": "E. ACT1 KO cells expressing either ACT1(WT) or ACT1(9ST mut) were stimulated with SF-IL-17 (500 ng/ml) as indicated or were left unstimulated and IL-17 was added post lysis. IL-17RSC was isolated via anti-Flag immunoprecipitation and analyzed by immunoblotting.",
    "ncbi_link": "ACT1: 109776"
  },
  {
    "caption": "F. ACT1 KO cells were reconstituted with either ACT1(WT) or ACT1(Δ20-380). Cells were stimulated with IL-17 (500 ng/ml) as indicated and lysates were analyzed by immunoblotting. * indicates nonspecific band.",
    "ncbi_link": "ACT1: 109776"
  },
  {
    "caption": "A, Top: Scheme of the sites targeted by sgRNA in the generation of AGO1x mutant cell lines. Bottom: Western analysis of lysates from mutant MDA-MB-231 cells showing the depletion of AGO1x and the comparable total AGO1 levels across the cell lines. Three independently collected sets of cells were lysed and analysed in parallel. After calculating the levels of AGO1x and AGO1 relative to GAPDH, values corresponding to individual lanes were normalized to the average over the replicates of the control line. These numbers are indicated below the blots. The P-values of the t-tests comparing the expression AGO1x in mutant (W1A and W6A) and control (CTRL) lines were W1A-CTRL: 0.0008, W6A-CTRL: 0.0002, and for AGO1 W1A-CTRL: 0.1227, W6A-CTRL: 0.1173.",
    "ncbi_link": "AGO1: 26523"
  },
  {
    "caption": "a representative immunofluorescence image of siPNPT1/siControl-treated control and W6A mutant MDA-MB-231 cells stained with J2 antibody (red). DAPI was used to mark the nucleus (blue) (G). The right-most panels show a magnification of the cells enclosed by the white boxes in the middle panels.",
    "ncbi_link": "PNPT1: 87178"
  },
  {
    "caption": "C. Dissociation constants (Kd) of Ago2-miRNA complexes (containing an AU-rich supplementary region) binding to target RNAs with bridging regions of various lengths. D. Dissociation constants (Kd) of Ago2-miRNA complexes (containing an GC-rich supplementary region) binding to target RNAs with bridging regions of various lengths. Data information: All plotted data are the means of at least three independent replicates. Error bars indicate SEM.",
    "ncbi_link": "Ago2: 27161
miRNA: 406906"
  },
  {
    "caption": "E. Fold repression of a luciferase reporter (relative to no target site control) plotted versus affinity (1/Kd) values measured for the same sites in vitro. Data information: All plotted data are the means of at least three independent replicates. Error bars indicate SEM.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "A. Top: schematic of miR-122 isomiRs paired with a target complementary to the seed region only. Bottom: release of the seed-paired target from Ago2-miR complexes was assessed by monitoring the fraction of the total target RNA bound as a function of time. B. Top: schematic of miR-122 isomiRs paired with a target complementary to the seed and supplementary (g13-g17) regions. Bottom: fraction target bound to the Ago2-miR complexes as a function of time. C. Top: schematic of miR-122 isomiRs paired with a target complementary to the seed and shifted supplementary (g15-g19) regions. . Bottom: fraction target bound to the Ago2-miR complexes as a function of time. Data information: All plotted data are the means of at least three independent replicates. Error bars indicate SEM.",
    "ncbi_link": "Ago2: 27161
miR: 406906
miR-122: 406906"
  },
  {
    "caption": "(A)- (D) Hepatocytes accumulate apical bulkheads upon bile duct ligation (BDL) and MDR2 KO. (A)-(B) Overview images of (A) murine liver tissue after control surgery or bile duct ligation (BDL) for 24h (N=3 biological replicates), or (B) control and MDR2 KO mice after 12 weeks (N=3 biological replicates). Immunofluorescence for the apical membrane marker CD13 (magenta), F-Actin (green) and nuclei (grey). Representative images are shown. Scale bar 10 µm. (C)-(D) High-resolution imaging of individual bile canaliculi in murine liver tissue (C) after control and 24h BDL surgery, or (D) in control and MDR2 KO mice, stained for F-Actin (green). Representative images are shown. Scale bar 2 µm. Apical bulkheads are highlighted with red arrowheads.",
    "ncbi_link": "MDR2: 18670"
  },
  {
    "caption": "(C) -(D) DCA treatment induces a cholestatic response in primary hepatocytes. Gene expression analysis of genes involved in bile acid metabolism and transport in primary hepatocytes treated with DMSO or 200 µM DCA for 16h. Represented are mean Cq values normalized to Gapdh expression (N=4 biological replicates). One sample t-test *P < 0.05, ***P < 0.001. (C) Abcb11/Bsep, (D) Cyp7a1/Cyp7. Data information: Boxplots show the 25th and 75th percentiles and the central band shows the median value. Whiskers extend to the min and max values.",
    "ncbi_link": "Abcb11: 27413
Bsep: 27413
Cyp7a1: 13122
Cyp7: 13122
Gapdh: 14433"
  },
  {
    "caption": "(D)- (E) Pharmacological inhibitors do not affect key bile acid signalling pathways. Gene expression analysis of different genes involved in bile acid signalling in primary hepatocytes treated with DMSO or 200 µM DCA with 200 µM Phloretin and 1 µM Ouabain for 16h. Represented are mean Cq values normalized to Gapdh expression and whiskers show min and max values (N=5 biological replicates). Unpaired t-test. (D) Cyp7a1/Cyp7, (E) Nr0b2/Shp. Data information: Boxplots show the 25th and 75th percentiles and the central band shows the median value. Whiskers extend to the min and max values.",
    "ncbi_link": "Cyp7a1: 13122
Cyp7: 13122
Gapdh: 14433
Nr0b2: 23957
Shp: 23957"
  },
  {
    "caption": "B) Total T cells were enriched from spleens of Ptpn6fl/fl/Ptpn11fl/flWbm, CD4cre Ptpn6fl/fl/Ptpn11fl/flWbm, CD4cre Ptpn6fl/fl mice. Expression of Ptpn6 and Ptpn11 was tested by immunoblot in cell lysates, Gapdh used as loading control.",
    "ncbi_link": "CD4: 12504
cre: 2777477
Ptpn11: 19247
Ptpn6: 15170"
  },
  {
    "caption": "CD4cre Ptpn6fl/fl and control mice were subcutaneously injected with MC38 cells. Tumour growth in individual mice is shown for the indicated genotypes and treatments; number of mice eradicating the tumour is shown within the graphs (C).",
    "ncbi_link": "CD4: 12504
cre: 2777477
Ptpn6: 15170"
  },
  {
    "caption": "CD4cre Ptpn6fl/fl and control mice were subcutaneously injected with MC38 cells. Survival curves are shown (D).",
    "ncbi_link": "CD4: 12504
cre: 2777477
Ptpn6: 15170"
  },
  {
    "caption": "individual mice challenged with MC38 and subsequently treated with anti-PD-1 antibody or isotype control is shown for each indicated genotype Survival curves of CD4cre Ptpn6fl/fl/Ptpn11fl/flWbm and control mice is shown (H).",
    "ncbi_link": "CD4: 12504
cre: 2777477
Ptpn11: 19247
Ptpn6: 15170"
  },
  {
    "caption": "I, J) 10-12 days following MC38 tumour inoculation and treatment with anti-PD-1 antibody or isotype control, CD4cre Ptpn6/11wt/wt and CD4cre Ptpn6fl/fl/Ptpn11fl/flWbm mice were sacrificed, and TILs analysed. Graphs depict frequencies of CD8+ T cells (gated as CD45+ TCRβ+ CD8+) expressing IFN-γ and TNFα upon re-stimulation (G) and percentages of CD8+ T cells (H).",
    "ncbi_link": "CD4: 12504
cre: 2777477
Ptpn11: 19247
Ptpn6: 15170"
  },
  {
    "caption": "B) Ptpn6 and Ptpn11 copy number, as estimated through high resolution mass spectrometry in GzmBcre Ptpn6/11fl/fl and control CTLs.",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "C and D) GzmBcre R26R-YFP reporter mice were injected subcutaneously with MC38 cells and analysed after 11 days. Graphs show the percentage of YFP+ cells among CD45+ CD8+ TILs (C) and the percentage of PD-1+ cells among CD45+ CD8+ YFP+ TILs (D). Results depict n = 4 mice (C and D).",
    "ncbi_link": "YFP: 
cre: 2777477
GzmB: 14939"
  },
  {
    "caption": "GzmBcre Ptpn6/11fl/fl and control Ptpn6/11fl/fl mice were subcutaneously injected with MC38 cells. Survival curves and statistical comparisons between different groups are shown (E).",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "C) Numbers of CTLs (gated on CD8+ T cells) from Ptpn6/11fl/fl or GzmBcre Ptpn6/11fl/fl mice were counted daily by flow cytometry with the addition of DAPI to monitor dead cells.",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "D) Quantitative high-resolution mass spectrometry was used to resolve the proteome of Ptpn6/11fl/fl and GzmBcre Ptpn6/11fl/fl CTLs (day 7). The plot depicts protein copy number in control and GzmBcre Ptpn6/11fl/fl cells. Significantly altered proteins are indicated in red; selected examples are annotated. Results are based on n = 3 biological replicates and two-tailed, unequal-variance t-test on log10 transformed copy number per cell values was used to compare differences between experimental groups.",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "G) Graph illustrates the percentage of DAPI+ dead cells of Ptpn6/11fl/fl and GzmBcre Ptpn6/11fl/fl CTLs (gated on CD8+ T cells) at the indicated days as measured by flow cytometry.",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "H) Protein copy number of Tnfrsf1b and Mcl-1 in GzmB cre Ptpn6/11fl/fl and control CTLs, as estimated through high resolution mass spectrometry.",
    "ncbi_link": "cre: 2777477
GzmB: 14939
Ptpn6: 15170"
  },
  {
    "caption": "(C,D) Pexophagy experiments of Δatg30 (ϕ), wild‐type (Atg30) and Atg30 AIM mutant (Atg30W73A F76A) cells were done by fluorescence microscopy, following the degradation of peroxisomes labelled with BFP fused at its C‐terminus to the Ser-Lys-Leu peroxisomal targeting signal 1 (BFP-SKL) and biochemically by monitoring peroxisomal thiolase degradation. Vacuoles were labelled with FM4‐64. Scale bar, 5 μm.",
    "ncbi_link": "atg30: 8200351
Atg30: 8200351"
  },
  {
    "caption": "(F) . Δatg30 (ϕ) and Δatg30 cells complemented with Atg30-HA (Atg30) and several Atg30-HA mutants were immunoprecipitated (α‐HA IP) under pexophagy conditions. In addition, α‐HA IP of Δatg30 cells (ϕ) and Δatg30 cells complemented with Atg30-HA (Atg30) were incubated with (+) and without (−) λPP. Input: total lysate.",
    "ncbi_link": "atg30: 8200351"
  },
  {
    "caption": "(G) Pexophagy in atg30 mutants was monitored by following thiolase levels of oleate‐induced peroxisomes after shifting cells to SD‐N. aa, amino acid; AD, activation domain; AIM, Atg8‐family‐interacting motif; AOX, alcohol oxidase; BD, binding domain; GFP, green fluorescent protein; HA, haemagglutinin; IP, immunoprecipitation; λPP, λ protein phosphatase.",
    "ncbi_link": "atg30: 8200351"
  },
  {
    "caption": "(A2) Pexophagy experiments of Δatg30 cells complemented with appropriate wild‐type or mutant Atg30 proteins described in A1.",
    "ncbi_link": "atg30: 8200351"
  },
  {
    "caption": "(B2) Pexophagy experiments of Δatg30 cells complemented with the two Atg30 molecules described in B1.",
    "ncbi_link": "atg30: 8200351"
  },
  {
    "caption": "(C2) Pexophagy assays of Δatg30 cells complemented with Atg30 wild‐type and mutants. aa, amino acids; AD, activation domain; AIM, Atg8‐family‐interacting motif; BD, binding domain; HA, haemagglutinin.",
    "ncbi_link": "atg30: 8200351"
  },
  {
    "caption": "(A) Large phagophore membrane formation in WT and the Atg30 mutant cells monitored by GFP-Atg8 during pexophagy conditions.",
    "ncbi_link": "Atg30: 8200351"
  },
  {
    "caption": "(B) Localization of GFP-Atg11 during pexophagy of methanol‐induced peroxisomes in cells expressing WT or mutant Atg30 proteins. White arrows indicate correct localization and yellow arrows indicate mislocalization, or in case of Atg8 localization, indicate absence of phagophore membrane elongation. Peroxisomes were labelled with BFP-SKL and vacuoles with FM4‐64. Scale bar, 5 μm. GFP, green fluorescent protein; WT, wild type.",
    "ncbi_link": "Atg30: 8200351"
  },
  {
    "caption": "(A) Mitophagy experiments of WT (PPY12), Δatg5, Δatg32 (ϕ) and Δatg32 complemented with WT Atg32 (Atg32), Atg32 with a deletion of the sequence between the AIM and phosphosite required for Atg11 binding (Atg32WQVLSSS), Atg32 AIM mutant (Atg32W121A V124A), mutants of the Thr upstream of the Atg32 AIM (Atg32T119A) and mutants altered in the Ser required for Atg11 binding (Atg32S159A). The cells were grown in YPL medium and shifted to SD‐N. Mitophagy was followed by the transport of Tom20-mCherry to the vacuole by fluorescence microscopy. Mitophagy was classified as −no mitophagy,+few cells show mitophagy, +++ most cells show mitophagy and ++++ almost all the cells show mitophagy (the intensity and numbers of cells containing Tom20-mCherry in the vacuole was considered). Scale bar, 5 μm.",
    "ncbi_link": "atg32: 854660
atg5: 855954"
  },
  {
    "caption": "(B) P. pastoris Δatg32 cells (ΔPpatg32) expressing Tom20-GFP and expressing the indicated Atg32 mutants were cultured in YPL medium for 12, 18 and 36 h. Mitophagy was monitored by GFP appearance by immunoblotting with α‐GFP antibodies.",
    "ncbi_link": "atg32: 854660"
  },
  {
    "caption": "(D) Two‐hybrid protein-protein interaction analysis of ScAtg36, ScAtg8 and ScAtg11. The receptors were mutated at the AIM (Atg36F33A L36A), at serine(s) upstream of the AIM (Atg36S31A) and at the Atg11‐binding site (Atg36S97A).",
    "ncbi_link": "Atg36: 853254"
  },
  {
    "caption": "(E) S. cerevisiae Δatg36 cells (ΔScatg36) expressing thiolase-GFP and expressing the indicated Atg36 mutants were cultured in oleate medium until mid‐log growth and then shifted to SD‐N. Pexophagy was monitored by GFP appearance by immunoblotting with α‐GFP antibodies.",
    "ncbi_link": "atg36: 853254"
  },
  {
    "caption": "(F) Y3H analysis of ScAtg36 with ScAtg8 and ScAtg11. The Y3H technology is on the basis of the yeast two‐hybrid system but with the co‐expression of third protein as a competitor and indicated in the figure (NLS-ScAtg11 or NLS-ScAtg8). The positive control was the ScAtg36 mutant affected in Atg11 binding (ScAtg36S97A) or in Atg8 binding (ScAtg36S31A), which should be unaffected by the competition of NLS-ScAtg11 or NLS-ScAtg8, respectively. Appropriate auto‐activation and interaction controls were also included. AD, activation domain; AIM, Atg8‐family‐interacting motif; BD, binding domain; GFP, green fluorescent protein; WT, wild type; Y3H, yeast three‐hybrid.",
    "ncbi_link": "Atg11: 856162
Atg36: 853254
Atg8: 852200"
  },
  {
    "caption": "Expression of Tardbp, total Sort1 and exon 17b Sort1 mRNAs quantified by Q-PCR in primary hippocampal neurons infected with either scrambled or Tardbp shRNA lentiviruses. Values were first normalized to Gapdh mRNA levels, then plotted as average ± SEM relative to the value of scrambled shRNA (N=3 independent experiments; n=3 wells per condition in each experiment). ***, p<0.001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Gapdh: 14433
Sort1: 20661
Tardbp: 230908"
  },
  {
    "caption": "Western blots of cell lysates and culture supernatants showing TDP-43 and Sortilin expression in primary hippocampal neurons infected with scrambled or Tardbp shRNA lentiviruses. Uninfected cultures were used as an additional control. β-actin immunoblotting and Coomasise Blue staining were used to control equal loading of lysates and supernatants, respectively. Molecular weights are indicated in kDa. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "Representative photomicrographs of cultured hippocampal neurons infected with scrambled or Tardbp shRNA lentiviruses, immunolabled for BDNF (green), SCG2 (red) and counterstained with DAPI (blue) in orthogonal views (dashed lines) showing colocalization of BDNF and SCG2 in the soma (white arrows).",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "Colocalization between BDNF and SCG2-positive vesicles expressed as percentage of total BDNF immunoreactivity ±SEM in cultured hippocampal neurons infected with scrambled or Tardbp shRNA lentiviruses (N=3 independent experiments, n>50 individual cells per condition in each experiment). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "Colocalization between BDNF and SCG2-positive vesicles in hippocampal neurons infected with scrambled or Tardbp shRNA lentiviruses together with either EGFP or Sortilin rescue viruses. Histogram bars show average ± SEM BDNF/SCG2 colocalization expressed as percentage of total BDNF immunoreactivity (N=3 independent experiments, n>50 individual cells per condition in each experiment). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Sortilin: 20661
Tardbp: 230908"
  },
  {
    "caption": "BDNF secretion induced by KCl treatment assessed by in-situ BDNF ELISA in cultured hippocampal neurons infected with scrambled or Tardbp shRNA lentiviruses. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=3 independent experiments; n=3 wells per condition in each experiment). *, p<0.05; ***, p<0.001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "BDNF secretion in cultured hippocampal neurons infected with scrambled (left) or Tardbp (right) shRNA lentiviruses together with either EGFP, Sort1 shRNA or Sortilin rescue viruses. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=3 independent experiments; n=3 wells per condition in each experiment). ***, p<0.001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Sort1: 20661
Sortilin: 20661
Tardbp: 230908"
  },
  {
    "caption": "Representative photomicrographs of TDP-43 (green) and NeuN (red) immunohistochemistry in hippocampal CA1 of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Arrows denote areas of depleted TDP-43 immunoreactivity in the mutant.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Percentage of TDP-43 positive cells relative to NeuN cells in CA1 and the remaining hippocampus (HC [-CA1]) of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SEM (N=3 mice per condition; 5 sections per mouse). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "TDP-43 intensity in TDP-43/NeuN double-positive cells in CA1 and the remaining hippocampus of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SEM (N=3 mice per condition; 5 sections per mouse). *, p<0.05; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Expression of Tardbp mRNA in micro-dissected CA1 and the remaining hippocampus of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice quantified by Q-PCR. Results are presented as average ± SEM relative to levels in Tardbpfx/fx mice, after normalization to Gapdh mRNA. (N=3 mice per condition; **, p<0.01). Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Gapdh: 14433
Tardbp: 230908"
  },
  {
    "caption": "Western blots of micro-dissected CA1 and the remaining hippocampus showing expression of TDP-43, full-length and truncated (soluble) Sortilin, and GAPDH in Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Bands corresponding to soluble Sortilin are indicated (black arrows). GAPDH immunoblotting was used to control for equal loading. Molecular weights are indicated in kDa. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "TDP-43 expression in micro-dissected CA1 and the remaining hippocampus of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SD of densitometry relative to GAPDH (N=3 mice per condition; **, p<0.01). Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Expression of exon 17b Sort1 and total Sort1 mRNAs in micro-dissected CA1 and the remaining hippocampus of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice quantified by Q-PCR. Results are presented as average ± SD relative to levels in Tardbpfx/fx mice, after normalization to Gapdh mRNA. (N=3 mice per condition; **, p<0.01 Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Gapdh: 14433
Sort1: 20661
Tardbp: 230908"
  },
  {
    "caption": "Expression of full-length (left) and truncated (soluble, right) Sortilin protein in micro-dissected CA1 and the remaining hippocampus of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SD of densitometry relative to GAPDH (N=3 mice per condition; **, p<0.01). Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Representative photomicrograph of Golgi staining in hippocampus of a Tardbpfx/fx mouse.",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "Sholl analysis of apical and basal dendritic arbors of CA1 pyramidal neurons from Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SEM (N=3 mice per condition, 20 neurons per mouse). *, p<0.05; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "High-magnification representative photomicrograph of Golgi staining of the dendritic arbour of a CA1 pyramidal neuron in a Tardbpfx/fx mouse. Black arrows denote selected dendritic spines.",
    "ncbi_link": "Tardbp: 230908"
  },
  {
    "caption": "Spine density in apical and basal dendrites of CA1 pyramidal neurons of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average ± SD (N=3 mice per condition, 15 sections per mouse; *, p<0.05; **, p<0.01). Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Representative photomicrographs of a CamKIIaCRE;Tardbpfx/fx hippocampus after stereotaxic injection of EGFP-expressing lentivirus immunostained for EGFP (green) and NeuN (red), and counterstained with DAPI (blue). The injected area within CA1 is indicated in the merged panel.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Expression of Tardbp (left), total Sort1 (center) and exon 17b Sort1 (right) mRNAs quantified by Q-PCR in micro-dissected CA1 of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice after injection of EGFP-expressing lentivirus or Sortilin rescue virus. Results are presented as average ± SEM relative to levels in Tardbpfx/fx mice injected with EGFP virus, after normalization to Gapdh mRNA. (N=3 mice per condition). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Gapdh: 14433
Sort1: 20661
Sortilin: 20661
Tardbp: 230908"
  },
  {
    "caption": "Spine density in apical dendrites of CA1 pyramidal neurons of Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice after injection of EGFP-expressing lentivirus or Sortilin rescue virus. Results are presented as average ± SEM (N=3 mice per condition, 15 sections per mouse). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Sortilin: 20661
Tardbp: 230908"
  },
  {
    "caption": "Percentage of change in field excitatory postsynaptic potential (fEPSP) recorded from hippocampal area CA1 after theta-burst stimulation (TBS) in Schaffer collaterals of hippocampal slices from Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice. Results are presented as average normalised to t=0 ± SEM (N=7 slices from 3 mice per condition). *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Percentage fEPSP change in CA1 after TBS in Schaffer collaterals of hippocampal slices from Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice stereotactically injected with EGFP-expressing lentivirus or Sortilin rescue virus (red) superimposed to the same data shown in panel (a) (black). Results are presented as average normalised to t=0 ± SEM (N=7 slices from 3 mice per condition). *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Sortilin: 20661
Tardbp: 230908"
  },
  {
    "caption": "Percentage fEPSP change in CA1 after TBS in Schaffer collaterals of hippocampal slices from Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice under control conditions (black) or with BDNF (200ng/ml) perfused from t=0 (green). Results are presented as average normalised to t=0 ± SEM (N=7 slices from 3 mice per condition). *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Percentage of total time spent in the target quadrant or in the remaining three quadrants of the Barnes maze for Tardbpfx/fx and CamKIIaCRE;Tardbpfx/fx mice at 3 different probe times: 20-30 min after first training session (short-term memory) and 24h or 14 days after last training session (long-term or remote memory, respectively). Results are presented as average ± SEM (N=8 mice per condition; * p < 0.05, ** p < 0.01, *** p < 0.001). Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "CamKIIa: 12322
CRE: 2777477
Tardbp: 230908"
  },
  {
    "caption": "Representative photomicrographs of cultured hippocampal neurons immunostained for TDP-43 (green), FLAG (red) and counterstained with DAPI (blue) in control conditions (untransduced) or infected with lentivirus expressing FLAG-tagged human TDP-43 12xQN construct.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "TDP-43 intensity in cell nuclei of untransduced or TDP-43 12xQN-infected hippocampal neurons normalized to mean nuclear intensity in untransduced neurons. Results are presented as average ± SEM (N=3 independent experiments; n=3 wells per condition in each experiment). Student's t-test; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using Student's t-test (B)",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "Expression of Tardbp (left), total Sort1 (center) and exon 17b Sort1 (right) mRNAs quantified by Q-PCR in hippocampal neurons untransduced (control) or infected with lentiviruses expressing Tardbp shRNA or human TDP-43 12xQN constructs. Values were first normalized to Gapdh mRNA levels, then plotted as average ± SEM relative to levels in untransduced neurons (N=3 independent experiments; n=3 wells per condition in each experiment). 1-way ANOVA with Tukey's post-hoc; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis",
    "ncbi_link": "Gapdh: 14433
Sort1: 20661
Tardbp: 230908
TDP-43: 23435"
  },
  {
    "caption": "BDNF secretion induced by KCl treatment as assessed by in-situ BDNF ELISA in cultured hippocampal neurons untransduced (control) or infected with lentiviruses expressing Tardbp shRNA or human TDP-43 12xQN constructs. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=5 independent experiments; n=5 wells per condition in each experiment). **, p<0.01; ***, p<0.001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis",
    "ncbi_link": "Tardbp: 230908
TDP-43: 23435"
  },
  {
    "caption": "BDNF secretion in cultured hippocampal neurons untransduced (control) or infected with lentiviruses expressing Tardbp shRNA or human TDP-43 12xQN constructs together with either EGFP or Sortilin rescue viruses. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=5 independent experiments; n=5 wells per condition in each experiment). **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis",
    "ncbi_link": "Sortilin: 20661
Tardbp: 230908
TDP-43: 23435"
  },
  {
    "caption": "Expression of Tardbp (left), total Sort1 (center) and exon 17b Sort1 (right) mRNAs quantified by Q-PCR in hippocampal neurons infected with Tardbp shRNA and mutant human TARDBP lentivirus constructs as indicated. Absolute levels of mouse Tardbp and human TARDBP mRNAs were determined using a standard curve and added together to assess total Tardbp mRNA levels relative to control uninfected cells after normalization to Gapdh mRNA. Results are presented as average ± SEM (N=3 independent experiments; n=3 wells per condition in each experiment). *, p<0.05; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Gapdh: 
Sort1: 20661
TARDBP: 23435
Tardbp: 230908"
  },
  {
    "caption": "Western blots of cell lysates showing total TDP-43 expression in primary hippocampal neurons infected with Tardbp shRNA and mutant human TARDBP lentivirus constructs as indicated. The antibody used here detects both mouse and human TDP-43 proteins. GAPDH immunoblotting was used to control for equal loading. Molecular weights are noted in kDa. Bands corresponding to mouse and human TDP-43 are indicated. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Tardbp: 230908
TARDBP: 23435"
  },
  {
    "caption": "BDNF secretion induced by KCl treatment assessed by in-situ BDNF ELISA in cultured hippocampal neurons infected with Tardbp shRNA and mutant human TARDBP lentivirus constructs as indicated. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=5 independent experiments; n=5 wells per condition in each experiment). *, p<0.05; ***, p<0.001 Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Tardbp: 230908
TARDBP: 23435"
  },
  {
    "caption": "BDNF secretion induced by KCl treatment in cultured hippocampal neurons infected with Tardbp shRNA and mutant human TARDBP lentivirus constructs together with either EGFP or Sortilin rescue viruses. Histogram bars show average ± SEM BDNF levels normalized to a standard curve (N=5 independent experiments; n=5 wells per condition in each experiment). *, p<0.05; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "Sortilin: 20661
Tardbp: 230908
TARDBP: 23435"
  },
  {
    "caption": "Expression of TARDBP (left), total SORT1 (center) and exon 17b SORT1 (right) mRNAs quantified by Q-PCR in human neurons derived from the indicated stem cells carrying either wild type Met337 (grey bars) or disease-associated Val337 (black bars) TARDBP alleles. Results are presented as average ± SEM (N=3 independent experiments; n=3 wells per condition in each experiment). *, p<0.05; **, p<0.01. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "SORT1: 6272
TARDBP: 23435"
  },
  {
    "caption": "BDNF secretion in stem-cell derived human neurons carrying wild type Met337or Val337 TARDBP alleles, infected with proBDNF lentivirus 5 days prior to depolarization by KCl treatment. Results are presented as average ± SEM (N=3 independent experiments; n=5 wells per condition in each experiment). **, p<0.01; ***, p<0.001. Data information: Results are presented as average ± standard error of the mean (SEM). All statistical tests were performed using 2-way ANOVA with Sidak post hoc analysis.",
    "ncbi_link": "BDNF: 627
TARDBP: 23435"
  },
  {
    "caption": "Left panel, a scheme of chromosome 18 copy number alterations depicting the distal long arm loss across TCGA Pan-Cancer dataset. Vertical red line indicates the localization of VPS4B. Right panel, enlarged fragment of chromosome 18 showing frequent deletions of VPSB locus in cancer samples. Deletions are marked in blue, amplified regions are marked in red. Analysis of VPS4B copy number alterations in TCGA Pan-Cancer dataset. Cancer types were sorted according to the mean VPS4B copy number after removing germline values.",
    "ncbi_link": "VPS4B: 9525
VPSB: 9525"
  },
  {
    "caption": "Scatter plot, analysis of VPS4B mRNA expression (number of transcripts per million) plotted against VPS4B copy number from TCGA CRC patient samples (n=376); plot generated using cBioPortal Gao et al, 2013(). Pie chart, summary of all types of VPS4B copy number alterations based on the analysis of data from 615 CRC samples deposited in the Colorectal Adenocarcinoma (TCGA, Provisional)",
    "ncbi_link": "VPS4B: 9525"
  },
  {
    "caption": "qPCR analysis of VPS4B mRNA abundance in normal colon, adenoma and CRC samples. Adenocarcinoma (n=26); adenoma (n=42); normal colon (n=24). Green horizontal bars indicate means and red whiskers indicate SD.",
    "ncbi_link": "VPS4B: 9525"
  },
  {
    "caption": "Analysis of viability of HCT116 cells assessed 96 h after transfection with independent non-targeting siRNA (two different duplexes used, siCTRL#1 or #2) or targeting VPS4A (duplexes #1 or #2), VPS4B (duplexes #1 or #2) or both VPS4 (various combinations of siVPS4A+siVPS4B duplexes). Data are means of 3 independent experiments ±SEM. All values were normalized, averaged (avrg) viability of siCTRL#1 and #2-transfected cells was set as 100%, the Kruskal-Wallis test followed by Dunn's multiple comparison post hoc test; ns - non-significant (p≥0.05), **p<0.01.",
    "ncbi_link": "VPS4A: 27183
VPS4: 27183///9525
VPS4B: 9525"
  },
  {
    "caption": "Left panel, analysis of clonogenic growth of HCT116 cells assessed 15 days after transfection with non-targeting (siCTRL#1), VPS4A- or/and VPS4B-targeting siRNAs used in various duplex combinations as indicated. Right panel, images of HCT116 clones taken at the day of clonogenic growth assessment. Data are means of 3 independent experiments ±SEM. NT - non-transfected. All values were normalized, clonogenic growth of siCTRL#1-transfected cells was set as 1. One-sample t-test; ns - non-significant (p≥0.05), ****p<0.0001.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Viability of RKO and SW480 cells assessed as in (A), growth of DLD-1 cells assessed in BrdU incorporation assay 96 h after siRNA transfection. Various independent non-targeting (siCTRL#1 or #2) and VPS4A- or B-targeting siRNA duplexes were used (#1, #2, #5 or #1, #2, respectively). All values were normalized, averaged (avrg) viability of siCTRL#1 and #2-transfected cells was set as 100%. Data are means of 3 independent experiments ±SEM. The Kruskal-Wallis test followed by Dunn's multiple comparison post hoc; ns - non-significant (p≥0.05), **p<0.01, ***p<0.001.",
    "ncbi_link": "VPS4A: 27183"
  },
  {
    "caption": "VPS4B copy number and dependency scores of selected cancer cell lines obtained in CRISPR/Cas9 and RNAi screens deposited in the DepMap portal (https://depmap.org/portal/).",
    "ncbi_link": "VPS4B: 9525"
  },
  {
    "caption": "VPS4B copy number status estimated across different cell lines using TaqMan assay. The whiskers represent the minimal and maximal copy number in a given triplicate readout. The BCL2 gene localized on 18q in the close vicinity to VPS4B was analyzed as a control.",
    "ncbi_link": "BCL2: 596
VPS4B: 9525"
  },
  {
    "caption": "Analysis of viability of HOP62 lung cancer cells assessed 144 h after transfection with independent non-targeting siRNA (two different duplexes used, siCTRL#1 or #2) or targeting VPS4A (duplexes #2 or #5), VPS4B (duplexes #1 or #2) or both VPS4 (various combinations of siVPS4A+siVPS4B duplexes). Data are means of 4 independent experiments ±SEM. All values were normalized, cell viability of averaged (avrg) siCTRL#1- and #2-transfected cells was set as 100%. Two-tailed unpaired t-test; ****p<0.0001.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525
VPS4: 9525///27183"
  },
  {
    "caption": "Analysis of viability of SNU410 pancreatic cancer cells assessed 168 h after transfection with independent non-targeting siRNA (three different duplexes used, siCTRL#1, #2 or #3) or targeting VPS4A (duplexes #2, #4 or #5), VPS4B (duplexes #1 or #2) or both VPS4 (various combinations of siVPS4A+siVPS4B duplexes). Data are means of 3 independent experiments ±SEM. All values were normalized, cell viability of averaged (avrg) siCTRL#1-, #2- and #3-transfected cells was set as 100%. Two-tailed unpaired t-test; ****p<0.0001.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525
VPS4: 9525///27183"
  },
  {
    "caption": "Left panel, growth of HCT116 VPS4B-/- shVPS4A cells as xenografts in mice in the presence or absence of doxycycline. Day 1 indicates the first day of doxycycline administration. n=9 for each group, each mouse bearing one tumor, ±SEM. Two-tailed unpaired t-test; ns - non-significant (p≥0.05), **p<0.01. Right panel, scatter plot representing end-point volumes of single xenografts. Bars represent means ±SEM.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Immunoblotting analysis of VPS4A abundance in xenograft samples from untreated and doxycycline-treated mice (6 separate xenograft samples for each group). Lysates of HCT116 VPS4B-/- cells transfected with control or VPS4A-targeting siRNA marked VPS4A protein detection. GAPDH served as a loading control.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Growth of HCT116 VPS4B-/- shCTRL#1 cells as xenografts in mice in the presence or absence of doxycycline. The arrow indicates the first day of doxycycline (Dox) administration. n=2 mice for each group, each mouse bearing two tumors, ±SEM.",
    "ncbi_link": "VPS4B: 9525"
  },
  {
    "caption": "Immunoblotting analysis of the canonical and noncanonical branches of the NF-κB pathway and mediators of caspase-dependent cell death. Lysates of HCT116 VPS4B-/- cells were collected 66 h after transfection with siRNA (siCTRL#1 or different siVPS4A duplexes: #2, #4 or #5). Lysates of HCT116 VPS4B+/+ and non-transfected HCT116 VPS4B-/- cells were used to monitor the basal pathway activity. Representative blot from 10 experiments is shown. NT- non-transfected; p-RelA - phospho-RelA; p-IκBα - phospho-IκBα; cl - cleaved caspases or PARP-1. GAPDH or vinculin served as loading controls.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Analysis of the impact of RIPK1 inhibitor (necrostatin-1) or pan-caspase inhibitor (Q-VD-Oph) on cell viability of HCT116 VPS4B-/- cells transfected with siRNA (non-targeting siCTRL#1 or different siVPS4A duplexes: #2, #4 or #5). Cell viability was assessed 72 h after siRNA transfection. Necrostatin-1 (50 µM), Q-VP-Oph (20 µM) or vehicle were added to the medium 48 h before viability assessment. Data are means of 5 independent experiments ±SEM. All values were normalized, viability of siCTRL-transfected and vehicle-treated cells was set as 100%. Two-tailed unpaired t-test; **p<0.01.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Measurement of ATP released to the cell medium by HCT116 VPS4B-/- cells non-transfected (NT) or transfected with siRNA (non-targeting siCTRL#1 or targeting siVPS4A duplexes: #2, #4 or #5). Cell culture media were exchanged 16 h after transfection, and fresh media were conditioned for the next 52-58 h. For non-transfected cells (NT), the same treatment protocol was used but without the transfection mixture.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Measurement of HMGB1 released to the cell medium by HCT116 VPS4B-/- cells non-transfected (NT) or transfected with siRNA (non-targeting siCTRL#1 or targeting siVPS4A duplexes: #2, #4 or #5). Cell culture media were exchanged 16 h after transfection, and fresh media were conditioned for the next 52-58 h. For non-transfected cells (NT), the same treatment protocol was used but without the transfection mixture.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Microscopy images presenting cell surface calreticulin (green) in HCT116 VPS4B-/- cells 48 h after transfection with siRNA (non-targeting siCTRL#1 or targeting siVPS4A#2). As a positive control for detection of cell surface calreticulin, non-transfected cells (NT) were treated with 2 µM mitoxantrone for 24 h. In blue, DAPI staining. Scale bar, 15 µm.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "Flow cytometric analysis of calreticulin exposed on the cell surface of VPS4A-depleted HCT116 VPS4B-/- cells 66 h after siRNA transfection (siVPS4A duplexes: #2, #4 or #5 were used). Non-transfected (NT) or siCTRL#1-transfected cells served as negative controls. Left panel, percentage of cells positive for calreticulin in the population of live (DAPI-negative) cells, data are means of 4 independent experiments ±SEM. The Mann-Whitney U test; **p<0.01. Right panel, representative dot plot diagrams of flow cytometric analysis of cell surface-exposed calreticulin. Primary rabbit anti-calreticulin and control isotype IgG antibodies were used for staining, followed by secondary AlexaFluor 647-conjugated antibody.",
    "ncbi_link": "VPS4A: 27183
VPS4B: 9525"
  },
  {
    "caption": "qPCR analysis of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophage polarization markers in mouse bone marrow-derived macrophages (BMDMs) incubated for 24 h in conditioned media (CM) collected from control (siCTRL#1), Vps4a- and/or Vps4b-depleted CT-26 cells. For double Vps4a+b depletion various combinations of siVps4a#2 or #5 and siVps4B#3 or #4 duplexes were used. Data were normalized and are presented as the fold change of expression of a given M1 or M2 marker in BMDMs treated with CM from Vps4-depleted cells compared to its expression in BMDMs treated with CM from siCTRL#1-transfected cells (set as 1). Data are means of 4 independent experiments ±SEM. One-sample t-test; ns - non-significant (p≥0.05), *p<0.05, **p<0.01.",
    "ncbi_link": "Vps4a: 116733
Vps4b: 20479
Vps4B: 20479
Vps4: 20479///116733"
  },
  {
    "caption": "d, LPS-primed bone-marrow-derived macrophages (BMDMs) from wild-type (WT), Nlrp3 or Ipaf deficient mice were stimulated for 6 h with MSU (150 µg ml−1), rotenone (10 µM for THP1 cells and 40 µM for BMDMs) or antimycin (40 µg ml−1 for THP1 cells and 10 µg ml−1 for BMDMs). The release of caspase-1 (western blot) was then determined. Data shown are representative of three independent experiments.",
    "ncbi_link": "Ipaf: 268973
Nlrp3: 216799"
  },
  {
    "caption": "b, THP1 cells stimulated with 3-methyladenine (3-MA, 10 mM) for 24 h or THP1 cells stably expressing shRNA against beclin 1 or ATG5 were stained with Mitotracker green and Mitotracker deep red for 30 min, and analysed by flow cytometry.",
    "ncbi_link": "ATG5: 9474
beclin 1: 8678"
  },
  {
    "caption": "c, LPS-primed BMDMs from wild-type, Nlrp3−/−, Asc−/− or Ipaf −/− knockout mice were stimulated with MSU (150 µg ml−1) or 3-MA (10 mM) for 6 h and the release of active caspase-1 and IL-1b was determined.",
    "ncbi_link": "Ipaf: 268973
Nlrp3: 216799
Asc: 66824"
  },
  {
    "caption": "d, THP1 cells stably expressing shRNA against beclin 1 or ATG5 were incubated for 24 h and media supernatants (SN) and inputs were analysed by western blotting.",
    "ncbi_link": "ATG5: 9474
beclin 1: 8678"
  },
  {
    "caption": "e, THP1 cells stably expressing shRNA against beclin 1 or ATG5 were stimulated with MSU or nigericin for 6 h. Data shown are representative of three independent experiments.",
    "ncbi_link": "ATG5: 9474
beclin 1: 8678"
  },
  {
    "caption": "f, THP1 cells stably expressing shRNA against NLRP3 were stimulated with nigericin and subcellular fractions analysed as in e.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "a, THP1 cells stably expressing shVDAC1 were stimulated with various NLRP inflammasome activators and then analysed for caspase-1 activation and IL-1b secretion.",
    "ncbi_link": "VDAC1: 7416"
  },
  {
    "caption": "b, THP1 cells expressing shRNA against VDAC2 were stimulated with MSU, R837, silica, alum or nigericin and analysed for IL-1b secretion.",
    "ncbi_link": "VDAC2: 7417"
  },
  {
    "caption": "c, THP1 cells expressing shRNA against VDAC1 were stimulated with MSU and nigericin, and NLRP3 localization was analysed by confocal microscopy. Scale bars: 20 µm.",
    "ncbi_link": "VDAC1: 7416"
  },
  {
    "caption": "(a) Kaplan-Meier survival curves of combined male and female WT and Atg5Tg mice no. 25 (P0.001; n=65 for WT mice and n=70 for Atg5Tg mice). (b,c) Lifespan extension in male Atg5Tg mice no. 25 (P0.001; n=32 for WT mice and n=36 for Atg5Tg mice no. 25) (b) and female Atg5Tg mice no. 25 (P0.001; n=33 for WT mice and n=34 for Atg5Tg mice no. 25) (c). (d-f) Kaplan-Meier survival curves of combined male and female WT and Atg5Tg mice no. 43 (d), no. 47 (e) and no. 471 (f) (P0.001; n=25 for WT mice and n=30 for Atg5Tg mice). P-values were calculated using the log-rank test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(g) Expression levels of Atg5 and Atg12-Atg5 conjugate, the conversion of LC3 I into LC3 II, and p62 level in the hearts of Atg5 Tg mice. Whole-tissue extracts were prepared from 3-month-old Atg5 Tg mice and WT littermates, and analysed by western blotting using the indicated antibodies. β-Actin served as a control. (h) Densitometric analysis of the signals on the blots shown in (g). The bars represent the mean±s.d. (n=3).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Western blot analysis showing enhanced levels of Atg5, Atg12-Atg5 conjugate and LC3 conversion, and reduced p62 levels in the indicated tissues of 18-month-old Atg5 Tg mice no. 25 (T) and WT mice (W). (b) Densitometric analysis of the signals on the blots shown in (a).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c) Electron microscopy images of autophagosomes (arrows) and late-autophagic compartments (arrowheads) in the liver tissues of 18-month-old Atg5 Tg mice no. 25 and WT mice. Scale bars are indicated. (d) The numbers of autophagosomes and autolysosomes per cell (n=50) in the electron microscopic images shown in (c) were counted. The bars represent the mean±s.d. ***P0.0001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(e) Fluorogenic comparison of basal autophagy activity between GFP-LC3 Tg mice and Atg5/GFP-LC3 double Tg mice. Whole bodies of 8-week-old male (left) and female (right) GFP-LC3 Tg (LC3), and LC3/LC3-LC3Tg mice (Atg5/LC3) were visualized using a Kodak Image Station 4000MM equipped with a filter set for FITC (Kodak Molecular Imaging Software, Version 4.0).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) Western blot analysis showing autophagy markers in the liver of GFP-LC3 mice. GFP-LC3 mice were injected for 5 days with siRNA-Atg5 or Atg5-HA cDNA through the tail vein. Whole-liver tissue lysates were prepared and subjected to immunoblotting using the indicated antibodies. β-Actin served as a control.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Representative physical pictures of 18-month-old WT and Atg5 Tg mice fed with a regular diet. (b) Body weight chart of ageing-induced obesity in WT and Atg5 Tg mice. The mice were fed with a regular diet for 24 months (n=180--250) and their body weights were monitored monthly. The bars represent the mean±s.d. ***P0.0001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(g) Enhanced glucose tolerance of Atg5 Tg mice. WT and Atg5 Tg mice were starved overnight and then given with an i.p injection of glucose (1 mg g−1 body weight). The results are the mean±s.d. of 12-week-old WT and Atg5 Tg mice (n=12). *P0.01, **P0.001, ***P0.0001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(h) Enhanced insulin sensitivity of Atg5 Tg mice. WT and Atg5 Tg mice were starved for 6 h and then i.p injected with 0.75 IU soluble insulin. *P0.01, **P0.001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(i) Plasma levels of triglycerol (TG) in WT and Atg5 Tg mice. The mice were fasted for 3 h before measurement. Young mice (4-week old, n=8); old mice (18-month old, n=8). ***P0.0001 versus control; Student's t-test",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(j) Plasma leptin levels in WT and Atg5 Tg mice (n=8-12). ***P0.0001 versus control; Student's t-test. (",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(l) Respiration rates of mitochondria in WT and Atg5 Tg MEFs (n=2).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(m) Wire-hang endurance test of Atg5 Tg and WT mice (n=10). All the bars represent the mean±s.d. ***P0.0001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Comparison of Atg12-Atg5 conjugate levels in WT and Atg5 Tg MEFs by western blot analysis. MEFs from WT and Atg5 Tg mice were cultured at embryonic day 13, after which cell extracts were examined by western blot analysis using anti-Atg5 and anti-β-actin antibodies.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(b) Increased conversion of LC3 and reduced expression of p62 in Atg5 Tg MEFs no. 6 by rapamycin and/or Baf.A1. WT MEFs no. 1 and Atg5 Tg MEFs no. 6 in passage number 3 were incubated for 48 h with 10 μM rapamycin in the absence or presence of Baf.A1, and cell extracts were then analysed by western blotting. The signals on the blot were quantified by densitometric analysis and represented as the ratio of p62 to β-actin.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c,d) Increased resistance of Atg5 Tg MEFs to oxidative stress. WT MEFs no. 1 and Atg5 Tg MEFs no. 6 were treated for 24 h with 50, 100, 200 and 300 μM H2O2 (c) or 300 μM H2O2 in the absence or presence of 5 mM 3-MA or 20 nM Baf.A1 (Baf.A1) (d). Cell viability was assessed by propidium iodide staining. The values are the mean±s.e.m. (n=3). **P0.001, ***P0.0001 versus control; Student's t-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(e) Representative photographs showing the resistance of Atg5 Tg MEFs to oxidative stress. Primary cultured WT and Atg5 Tg MEFs were treated with 300 μM H2O2 for 24 h and then observed under a light microscope. Scale bars, 50 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) Effect of oxidative stress on the autophagy activity in Atg5 Tg MEFs. WT MEFs no. 1 and Atg5 Tg MEFs no. 6 were treated with 100 μM H2O2 for 24 h in the presence or absence of 20 nM Baf.A1, and cell extracts were analysed by western blotting. About 10 and 30 μg of proteins were used for LC3 (upper panel) and p62 (bottom panel) detection, respectively. β-Actin served as a control.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "A) H1299 cell line was transfected with increasing concentrations of MDM2, and the RB+5´UTR exogenous (left panel) and endogenous (right panel) levels were evaluated. B) Evaluation of the RB expression as in (A) but inducing DNA damage with doxorubicin 1 µM during 16 h. ",
    "ncbi_link": "MDM2: 17246
RB: 5925"
  },
  {
    "caption": "C) Evaluation of the RB levels in an MDM2 dose-dependent fashion under normal and genotoxic stress induced by doxorubicin 16 h in HEK 293 cell line. D) Evaluation of the RB levels in a MDM2 dose-dependent fashion under normal and genotoxic stress induced by doxorubicin 16 h in C33 cell line. ",
    "ncbi_link": "MDM2: 17246"
  },
  {
    "caption": "E) Evaluation of the endogenous RB expression using H1299 cell line, under normal conditions, transfecting the cells with an increasing amount of the phosphomimetic mutant MDM2(S395D). F) Evaluation of the endogenous RB as in (E) but using C33 cell line. ",
    "ncbi_link": "MDM2: 17246"
  },
  {
    "caption": "A) Evaluation of RB mRNA levels, normalised by GAPDH, in an MDM2 dose-dependent manner. The H1299 cells were treated with doxorubicin during 16 h to induce genotoxic stress. Endogenous levels (upper panel); exogenous levels (middle panel); endogenous levels of RB but using the MDM2(S395D) under normal conditions (lower panel).",
    "ncbi_link": "GAPDH: 
MDM2: 17246
RB: 5925"
  },
  {
    "caption": "B) Kinetic of the endogenous RB expression in H1299 cell line from 0 to 48h. The cells were treated with cichlohexamide (CHX) was added to stop translation, under normal conditions (upper panel) and treated with doxorubicin (lower panel). The cells were transfected with MDM2.",
    "ncbi_link": "MDM2: 17246"
  },
  {
    "caption": "Different constructs of RB were transfected in H1299-RBKO treated with doxorubicin 16 h to induce genotoxic stress; the RB constructs levels of expression were evaluated using HA antibody. The bar diagrams show the quantification of the western blots data. A) Evaluation of the small pocket expression in an MDM2 dose-dependent manner. B) Cells were transfected with the RB large pocket construct. ",
    "ncbi_link": "MDM2: 17246
RB: 5925"
  },
  {
    "caption": "Different constructs of RB were transfected in H1299-RBKO treated with doxorubicin 16 h to induce genotoxic stress; the RB constructs levels of expression were evaluated using HA antibody. The bar diagrams show the quantification of the western blots data. C) Cells were transfected with RB full length without the 5´URT (named RB-HA). D) Cells were transfected with the RB full-length plus 260 nt of its own 5´ UTR (named RB+5´UTR). ",
    "ncbi_link": "HA: 
RB: 5925"
  },
  {
    "caption": "E) The binding of MDM2 to the RB mRNA in H1299 cells as estimated using RNA CoIP. Cells were treated with doxorubicin (1 µM for 16 h) or DMSO.",
    "ncbi_link": "RB: 5925"
  },
  {
    "caption": "F) RT-qPCR of RB and GAPDH of the MDM2-immunoprecipitation from the polysomal fractionation (see EV2D). Data are representative of three similar independent experiments.",
    "ncbi_link": "GAPDH: 
RB: 5925"
  },
  {
    "caption": "H) RNA-PLA assay using rabbit anti-MDM2 and a mouse biotin-antibody. H1299- RBKO was stable transfected with RB-HA or RB+5´UTR. Cell nuclei were visualised with DAPI blue. The red dots show the interaction between the protein and the mRNA. The scale bar corresponds to 20 μm.",
    "ncbi_link": "HA: 
RB: 5925"
  },
  {
    "caption": "C) Evaluation of increasing concentrations of MDM2 on the cell cycle of C33 cell line after genotoxic stress induced with etoposide, (EV; empty vector). D) The same as in (C) but under normal cellular conditions.",
    "ncbi_link": "MDM2: 17246"
  },
  {
    "caption": "C) In vitro RB ubiquitination by MDM2(S395D) in presence or absence of RB mRNA.",
    "ncbi_link": "RB: 5925"
  },
  {
    "caption": "D) A representative clonogenic assay. Increasing concentrations of MDM2 were transfected in H1299-RBKO stable transfected with RB-HA or RB+5´UTR. The cells were treated with doxorubicin to induce genotoxic stress conditions. Data are means ± s.d. of three independent experiments, student t test was used to calculate statistical significance (*p <0.05).",
    "ncbi_link": "HA: 
MDM2: 17246
RB: 5925"
  },
  {
    "caption": "E) Evaluation of cyclin E mRNA levels in an MDM2 dose-dependent manner. The H1299 cells were treated with doxorubicin during 16 h to induce genotoxic stress. Data are means ± s.d. of three independent experiments, student t test was used to calculate statistical significance (*p <0.05, ***p< 0.001).",
    "ncbi_link": "cyclin E: 898
MDM2: 17246"
  },
  {
    "caption": "(b) Wild type or STG-p62 Hap1 cells were mock or puromycin treated for 2 hours and stained for ubiquitin. The endogenous p62 was stained with an anti-p62 antibody in the parental Hap1 cells, while the fluorescence of the GFP tag was recorded in STG-p62 cells. Arrowheads indicate co-localizing puncta",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(b) Cluster formation assays were conduced with mCherry-p62 wt or LIR mutant in presence of GST-4xUb. Left: representative images of the samples two minutes after the addition of GST-4xUb. Middle: quantification of particle count. The dashed line indicates the time point of images displayed on the left. Right: input gel of the samples after reaction. The relative position of marker bands is indicated. For all graphs, averages and SDs from at least three independent replicates are shown",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(c) Top left: Western blots of lysates of CRISPR/Cas9 genome-edited STG-p62 wild type and LIR mutant cells. Clone Lir1B was used for the experiments shown in Figure 6c. Bottom left: Representative pictures of STG-p62 WT or LIR mutant Hap1 cells treated with Puromycin for 90 minutes and stained with anti-Ub conjugates antibody (FK2). Right: quantification of cytoplasmic p62 puncta per cell (top), and of their co-localization upon puromycin treatment (bottom). Averages and SDs from three independent experiments are shown. In total, at least 1440 number of cells were counted per condition",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(a,b) HeLa cells were treated with 10 μg ml−1 N-Shh peptide for 24 h.(b) mRNA was obtained and levels of Ptch1 or Gli1 and actin mRNA were amplified by standard PCR and visualized in agarose gels. Graph shows mRNA levels quantified by densitometric analysis and normalized to actin.",
    "ncbi_link": "actin: 
Gli1: 2735
Ptch1: 5727"
  },
  {
    "caption": "(c) 8xGli-luciferase construct was transfected in HeLa cells for 24 h, followed by treatment with 10 μM purmorphamine, or DMSO as a control, for another 24 h. Graph represents the mean value of the firefly luciferase activity relative to Renilla transfection control.",
    "ncbi_link": "firefly luciferase: 
luciferase: 
Renilla: "
  },
  {
    "caption": "(f) HA-HttQ74 construct was transfected into HeLa cells followed by treatment with 10 μM purmorphamine for 24 h. The percentage of transfected cells with aggregates detected by HA immunofluorescence is shown in the graph. P-values were calculated by odds ratio.",
    "ncbi_link": "Htt: 3064"
  },
  {
    "caption": "(g) U20S cells stably expressing HaloTag-p62 were labelled with HaloTag ligand for 15 min and washed out followed by treatment with purmorphamine. After 48 h, cells were lysed, run on a SDS-polyacrylamide gel electrophoresis and fluorescent HaloTag was visualized using a Typhoon 8600 variable mode imager. Fluorescence was normalized to total protein levels, detected on the same gels by Kryton Fluorescence protein stain. A representative gel and its quantitated normalized levels are shown. In all panels, graphs show mean values and error bars represent s.d. from a triplicate experiment representative of at least three independent experiments. Statistical analyses were performed by two-tail Student's t-test unless indicated: ***P0.001; **P0.01; *P0.05. SDS-PAGE, SDS-polyacrylamide gel electrophoresis.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(a) HeLa cells were transiently transfected with pcDNA (vector), Ptch1 or Ptch2 constructs for 48 h. Where indicated, cells were treated with bafA1 for the last 4 h. LC3-II levels were detected by western blotting and levels were quantified by densitometric analysis relative to tubulin and shown in graph.",
    "ncbi_link": "pcDNA: 
Ptch1: 5727
Ptch2: 8643"
  },
  {
    "caption": "(b) HeLa were transfected with Ptch1 or Ptch2 together with HA-HttQ74 and the percentage of transfected cells with aggregates was assessed by HA immunofluorescence. P-values were calculated by odds ratio.",
    "ncbi_link": "Htt: 3064
Ptch1: 5727
Ptch2: 8643"
  },
  {
    "caption": "(c) Atg5+/+ or Atg5−/− MEFs were transfected with GFP-HttQ74 for 48 h, cells were fixed and the percentage of transfected cells with aggregates was scored by direct fluorescence.",
    "ncbi_link": "Atg5: 11793
Htt: 3064"
  },
  {
    "caption": "(d,e) Endogenous LC3-II levels were detected in HeLa cells transfected with control, Ptch1 or Ptch2 siRNA and either left untreated or treated with 100 mM trehalose in the last 24 h (d) Quantification and statistical analysis is shown in graphs.",
    "ncbi_link": "Ptch1: 5727
Ptch2: 8643"
  },
  {
    "caption": "(d,e) Endogenous LC3-II levels were detected in HeLa cells transfected with control, Ptch1 or Ptch2 siRNA and either left untreated or treated with400 nM bafA1 for 4 h (e). Quantification and statistical analysis is shown in graphs",
    "ncbi_link": "Ptch1: 5727
Ptch2: 8643"
  },
  {
    "caption": "(f) siRNA-targeting Ptch2 was transfected into HeLa cells stably expressing mRFP-GFP-LC3 and representative confocal microscopy images are shown. Scale bars represent 26 μm. Percentage of GFP-positive vesicles (autophagosomes), RFP-positive vesicles (total number of vesicles) or percentage of autolysosomes (calculated by subtracting numbers of GFP from RFP vesicles), quantified using a Cellomics array scan, was calculated relative to control siRNA-transfected cells. Although an increase in autophagosome biogenesis generally increases both the number of GFP+ vesicles and the number of GFP-/RFP+ vesicles as a result of an enhanced autophagy flux, defects in autophagosome degradation, such as in bafA1-treated cells, increase GFP+ vesicles but not GFP−/RFP+ structures, as GFP remains intact. Graph shows the mean value obtained from four independent experiments in triplicate and with control conditions set to 100. In all panels, unless indicated, graphs show mean values and error bars represent s.d. from a triplicate experiment representative of at least three independent experiments. Statistical analyses were performed by two-tail Student's t-test: **P0.01; *P0.05; NS, not significant.",
    "ncbi_link": "LC3: 440738///81631///84557
Ptch2: 8643"
  },
  {
    "caption": "(a) Smo siRNA-treated cells were transfected with HA-HttQ74 for the last 24 h and the percentage of transfected cells with aggregates scored in HA-positive cells by immunofluorescence. Graphs show mean values and error bars represent s.d. of a representative experiment performed in triplicate. P-values were calculated by odds ratio.",
    "ncbi_link": "Htt: 3064
Smo: 6608"
  },
  {
    "caption": "(b) siRNA-targeting Smo was transfected into HeLa cells stably expressing mRFP-GFP-LC3. Representative confocal microscopy images are shown. Bars represent 26 μm. The number of vesicles was analyzed in a Cellomics array scan and percentage was calculated relative to control siRNA-transfected cells. Statistical tests were performed on data from three independent experiments in triplicate. *P0.05; ***P0.001.",
    "ncbi_link": "LC3: 440738///81631///84557
Smo: 6608"
  },
  {
    "caption": "(a) Wild-type Gli+/+ or Gli1−/−, Gli2−/− and Gli3−/− MEFs were treated with 100 mM trehalose alone or in combination with 10 μM of Pmph for 24 h, or left untreated. Total cell lysates were subjected to immunoblot with anti-LC3 and anti-actin antibodies.",
    "ncbi_link": "Gli1: 14632
Gli2: 14633
Gli3: 14634
Gli: 14634///14633///14632"
  },
  {
    "caption": "(b) Gli2−/− MEFs were transfected for 48 h with either empty vector or Gli2 DNA construct and treated as in a. with 100 mM trehalose alone or in combination with 10 μM of Pmph for 24 h, or left untreated. Total cell lysates were subjected to immunoblot with anti-LC3 and anti-actin antibodies.",
    "ncbi_link": "Gli2: 14633"
  },
  {
    "caption": "(c) LC3-II levels were detected by western blotting of total lysates from wild-type and Gli2−/− mice embryos (E12.5). For quantification, LC3-II levels from a total of five wild-type and five Gli2−/− embryos were normalized to actin, wild-type was set to 100. Graphs show mean values and error bars represent s.d. Statistical analysis were performed by two-tail Student's t-test **P0.01. Pmph, purmorphamine.",
    "ncbi_link": "Gli2: 14633"
  },
  {
    "caption": "(a,b) Control (a) or hh[ts2] (b) larvae were incubated at permissive temperature (18 °C) to the third instar stage, then cultured at non-permissive temperature (29 °C) in well-fed conditions for 24 h. Dissected fat body tissue was incubated in Lysotracker Red and DAPI and imaged unfixed.",
    "ncbi_link": "hh: 42737"
  },
  {
    "caption": "(c) Lysotracker Red-labelled fat body containing single-cell flipout clones (GFP positive) overexpressing patched. Fat body was dissected from well-fed larvae, incubated in Lysotracker Red/DAPI and imaged unfixed.",
    "ncbi_link": "patched: 35851"
  },
  {
    "caption": "(d) Confocal image of a GFP-positive patched-expressing clone, with mCherry-Atg8a expressed in all cells. Fat body was dissected from well-fed larvae and imaged after formaldehyde fixation.",
    "ncbi_link": "Atg8a: 32001
patched: 35851"
  },
  {
    "caption": "(e) GFP-marked flipout clones of CiCell-expressing cells. Fat body was dissected from well-fed larvae, incubated in Lysotracker Red/DAPI and imaged unfixed.",
    "ncbi_link": "CiCell: 43767"
  },
  {
    "caption": "(f) Confocal image of fixed mCherry-Atg8a expressing fat body containing a GFP-marked clone of CiCell-expressing cells.",
    "ncbi_link": "Atg8a: 32001
CiCell: 43767"
  },
  {
    "caption": "(g) Cells homozygous for the null costal2[2] allele (marked by lack of GFP) were generated by flp/FRT-mediated recombination in mCherry-Atg8a expressing fat body. Larvae were starved 4 h before dissection and fixation.",
    "ncbi_link": "Atg8a: 32001
costal2[2]: 35653"
  },
  {
    "caption": "(e,f) Wild-type and PERK−/− (e) or eIF2α S51A/S51A MEFs (f) were treated with DMSO or 10 μM purmorphamine for 24 h and, where indicated, cells were treated with bafA1 for the last 4 h. tubulin-II and tubulin or tubulin, as a loading control, were detected and a representative blot is shown. HBSS, Hank's balanced salt solution.",
    "ncbi_link": "PERK: 13666
eIF2α: 13665"
  },
  {
    "caption": "Anti-Flag Western Blot for transiently transfected FlagSLC25A51 variants and empty vector control in HeLa cells; HSP60, loading control.",
    "ncbi_link": "Flag: 
SLC25A51: 92014"
  },
  {
    "caption": "Free mitochondrial NAD+ levels measured using a ratiometric biosensor in HeLa cells expressing empty vector control (n = 25 biological replicates), wildtype FlagSLC25A51 (n = 25 biological replicates), and indicated mutants (n = 4 - 6 biological replicates). Measurements were taken at 24 hours post-transfection; the dashed line indicates the baseline defined by the empty vector control, and red denotes data equivalent to wildtype. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, ANOVA p <0.0001 with post-hoc Dunnett's test compared to empty vector control, *p < 0.05, **p < 0.01. (bottom) Protein expression from HeLa cells transiently transfected with empty vector control, wildtype FlagSLC25A51 and the indicated variants using anti-Flag western blot; HSP60, loading control.",
    "ncbi_link": "Flag: 
SLC25A51: 92014"
  },
  {
    "caption": "Quantitation of uptake of 32P-NAD+ after 1 hour by E. coli cells expressing wildtype SLC25A51 (amino acids 29-297) and the indicated mutants; wildtype activity and equivalent, red. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, n = 5 - 8 biological replicates, ANOVA p <0.0001 with post-hoc Dunnett's test compared to wildtype, ***p < 0.001.",
    "ncbi_link": "SLC25A51: 92014"
  },
  {
    "caption": "Free mitochondrial NAD+ levels measured using a ratiometric biosensor in HeLa cells co-expressing empty vector control (n = 8 biological replicates), wildtype FlagSLC25A51 (n = 8 biological replicates), and indicated mutants (n = 4 biological replicates). Measurements were taken at 24 hours post-transfection; the dashed line indicates the baseline defined by the empty vector control, and red denotes data equivalent to wildtype. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, ANOVA p < 0.0001 with post-hoc Dunnett's test compared to empty vector control ***p < 0.001. (bottom) Protein expression from HeLa cells transiently transfected with empty vector control, wildtype FlagSLC25A51 and the indicated variants using anti-Flag western blot; HSP60, loading control.",
    "ncbi_link": "Flag: 
SLC25A51: 92014"
  },
  {
    "caption": "Relative uptake of 32P-NAD+ after 1 hour by E. coli cells expressing wildtype SLC25A51 (amino acids 29-297) or the E132A mutant when competed by 100 μM (n = 3 biological replicates) and 250 μM (n = 4 biological replicates) unlabeled NAD+ (red) or NADH (black). Data is shown as floating bars with central line at mean and the box represents the min and max value, unpaired two-sided t-test *p < 0.05.",
    "ncbi_link": "SLC25A51: 92014"
  },
  {
    "caption": "Quantitation of 32P-NAD+ uptake after 1 hour in E. coli cells expressing wildtype SLC25A51 (amino acids 29-297) and indicated mutants; wildtype activity (n = 19 biological replicates) and equivalent, red. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, n = 5 - 8 biological replicates, ANOVA p <0.0001 with post-hoc Dunnett's test compared to wildtype ***p < 0.001.",
    "ncbi_link": "SLC25A51: 92014"
  },
  {
    "caption": "Free mitochondrial NAD+ levels measured using a ratiometric biosensor in HeLa cells expressing empty vector control (n = 27 biological replicates), wildtype FlagSLC25A51 (n = 27 biological replicates), and indicated mutants (n = 4 - 7 biological replicates). Measurements were taken at 24 hours post-transfection; the dashed line indicates the baseline defined by the empty vector control, and red denotes data equivalent to wildtype. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, ANOVA p < 0.0001, post-hoc Dunnett's test compared to empty vector control ***p < 0.001. (bottom) Protein expression from HeLa cells transiently transfected with empty vector control, wildtype FlagSLC25A51 and the indicated variants detected by anti-Flag western blot; HSP60, loading control.",
    "ncbi_link": "Flag: 
SLC25A51: 92014"
  },
  {
    "caption": "Free mitochondrial NAD+ levels measured using a ratiometric biosensor in HEK293 SLC25A51 KO cells expressing empty vector control, wildtype FlagSLC25A51, and indicated mutants. Measurements were taken at 48 hours post-transfection; the dashed line indicates the baseline defined by the empty vector control, and red denotes data equivalent to wildtype. Data are shown in box and whisker format, with hinges at 25th and 75th percentiles, whiskers represent min and max and the line is the median, n = 4 - 6 biological replicates, ANOVA p < 0.0001, post-hoc Dunnett's test compared to empty vector control **p < 0.01, ***p < 0.001. (bottom) Protein expression from HEK293 SLC25A51 KO cells transiently transfected with empty vector control, wildtype FlagSLC25A51 and the indicated variants detected with anti-Flag western blot; HSP60, loading control.",
    "ncbi_link": "Flag: 
SLC25A51: 92014"
  },
  {
    "caption": "Schistosomal- miRNA was extracted from either EVs that were isolated from schistosomal-growing medium or control pellets that were isolated from unused schistosomal-medium as described in the Materials and Methods (Schistosomal-EVs purification section). Equal aliquots were subjected to qRT-PCR with specific primers to the schistosomal-miR-10, Bantam and miR-125; the expression is presented as ∆Ct from background Ct that was set as 40 cycles.",
    "ncbi_link": "miR-125: 
Bantam: RF00727
miR-10: RF00104"
  },
  {
    "caption": "The trans-well system was performed as in Fig. 1. Schistosome-exposed Th cells or control Th cells were subjected to qRT-PCR with specific schistosomal-Taqman primers to (A) miR-10-5p, (B) Bantam, and (C) miR-125b.",
    "ncbi_link": "miR-125b: 
Bantam: RF00727
miR-10-5p: RF00104"
  },
  {
    "caption": "The trans-well system was performed as in Fig. 1. The Control wells contained only unused schistosomal-medium; Supernatant wells contained 0.1 μm of the filtered schistosomal-growing medium; Th wells contained sorted CD4+CD11c- from spleens; Th+APCs contained sorted CD4+CD11c- and CD4-CD11c+ in 5:1 ratio, respectively. In Data information: In (A-E) the expression is presented as arbitrary units calculated as 2∆∆CT of miRNA relative to snRNA U6 and in (F) mRNA relative to β2 microglobulin. The mean +/- SEM was calculated from at least 3 independent experiments (except in F of 2 independent experiments).",
    "ncbi_link": "U6: 
β2 microglobulin: "
  },
  {
    "caption": "Th cells were isolated from the indicated lymph nodes and spleen. In the case of uninfected mice, the Th cells from different lymph nodes and the spleen were mixed. qRT-PCR was performed with specific Taqman primers to either schistosomal-miR-10 or -Bantam. The presence of the miRNAs is presented as arbitrary units calculated as 2∆∆CT of the miRNA divided by snRNA U6. The mean +/- SEM was calculated from 4 independent experiments.",
    "ncbi_link": "U6: 
Bantam: RF00727
miR-10: RF00104"
  },
  {
    "caption": "HEK-293 cells were transfected with a plasmid expressing schistosomal-miR-10 at the indicated concentration together with either psiCHECK-II vector, psiCHECK-WT-MAP3K7-3'UTR or psiCHECK-mut-MAP3K7. After 24h, the cells lysates were subjected to luciferase assay. The results are presented as the ratio of renilla/luciferase expression that was normalized relative to cells transfected only with psiCHECK-II. Values are expressed as the mean+/-SD of at least 3 independent experiments.",
    "ncbi_link": "luciferase: 
MAP3K7: 6885
miR-10: RF00104"
  },
  {
    "caption": "A representative experiment in which protein extracted from Jurkat-T cells stably over expressing stably control vector or miR-10 expressing vector were subjected to WB analysis with anti-MAP3K7 or anti-GAPDH antibodies. The graph presents densitometry analysis of 3 WBs analyses performed as in (C). The mean +/- SD was calculated from 4 independent experiments. Statistics were performed using t-test (*p<0.05).",
    "ncbi_link": "miR-10: RF00104"
  },
  {
    "caption": "Jurkat-T cells stably expressing either control vector or a vector containing schistosomal-miR-10 were co-transfected with a control Luciferase plasmid or NF-κB luciferase reporter vector. In all transfections, a plasmid expressing Renilla vector as an internal control was added. 48h post-transfection, cells were harvested and were analyzed by luciferase reporter assay. Values were normalized to the Renilla activity. Data are represented as mean +/-SEM from 5 independent experiments. Statistics were performed using t-test, **p<0.01.",
    "ncbi_link": "Luciferase: 
luciferase: 
miR-10: RF00104"
  },
  {
    "caption": "(C) LacZ staining (blue) to detect gene expression of the knocked-in LacZ cassette from the Abca12 locus in islets (islet outlined, scale bar = 25μm).",
    "ncbi_link": "LacZ: 
Abca12: 74591"
  },
  {
    "caption": "(D,E) ABCA12 immunostaining and the development of hyperkeratotic skin disease in E18.5 Abca12tm1a/tm1a mouse embryos (brackets indicate thickened epidermis, dashed line indicates epidermal basement membrane, scale bar = 50μm).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(H) Detection of recombination of the Abca12 locus by PCR, indicating different alleles (tm1c, wild type and tm1d).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(A-F) Oral and intraperitoneal glucose tolerance testing in Abca12tm1d mice at 6 (A,B), 8 (C, D) and 12 weeks (E,F) (mean±SEM, n=4-9 mice per group, * p=<0.05, **p<0.01 Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(H) Whole blood Hb1Ac levels in 16 week old Abca12tm1d mice (mean±SEM, n=4-9 mice per group, **p<0.01 Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(I) Acute phase insulin secretion after intraperitoneal injection of glucose (mean±SEM, n=4-9 animals per group, white/grey/black = Abca12+/+, cre/+ and Abca12tm1d respectively, mice at 8 weeks of age, **p<0.01 Students t-test).",
    "ncbi_link": "Abca12: 74591
cre: 2777477"
  },
  {
    "caption": "(J) Silencing of ABCA12 in MIN6 cells as assessed by Western blot of ABCA12 immuno-precipitate (top panel) or confocal microscopy in cells transfected with Dy547-siRNAABCA12 (lower panel, scale bar = 10μm).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(K) Glucose stimulated insulin secretion (GSIS) from MIN6 cells after silencing of ABCA12 (mean±SEM, n=4 replicates from assays in quadruplicate, ***p<0.0001, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(L) Cellular insulin content in MIN6 cells after silencing of ABCA12 (mean±SEM, n=4 replicates from assays in quadruplicate).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(D) Western blot of cell lysates of MIN6 cells after silencing of Abca12, probed with antibodies against ABCA1, ABCG1, SR-B1 and LXRβ.",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(E) Total cholesterol (COH) or cholesteryl esters (CE) levels in isolated pancreatic islets of mice at 8 weeks of age with deletion of Abca12 in β-cells (mean±SEM n=9, 5 and 5 mice per genotype respectively).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(F) Ceramides levels in isolated pancreatic islets of mice at 8 weeks of age with deletion of Abca12 in β-cells (mean±SEM n=10, 4 and 5 mice per genotype respectively).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(G) Lipid levels in MIN6 cells in which ABCA12 had been depleted by siRNA treatment (mean±SEM, n=5 (biological replicates assayed in triplicate), FC = free cholesterol, CE = cholesterol ester, Cer = ceramide, SM = sphingomyelin, TG = triacylglycerol, PC = phosphatidylcholine, *p<0.05, **p=<0.01, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(H) Cholesterol efflux to lipid-free apoA-I (30 μg/ml, 2 h) from MIN6 cells transfected with siRNAscr or siRNAABCA12 and activated or not with TO901317 (4 μM)(mean±SEM, n=4, (biological replicates assayed in triplicate), *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(I) Cholesterol efflux to HDL (30 μg/ml, 2 h) from MIN6 cells transfected with siRNAscr or siRNAABCA12 and activated or not with TO901317 (4 μM); (mean±SEM, n=4 (biological replicates assayed in triplicate)).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(J) The effect of overexpression of ABCA1 on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates assayed in triplicate), *p=<0.05, Students t-test), inset shows a Western blot of cell lysates probed with anti-ABCA1 antibody in which the order of bands corresponds to the order of bars).",
    "ncbi_link": "ABCA1: 11303
ABCA12: 74591"
  },
  {
    "caption": "(K) The effect of overexpression of ABCG1 on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates assayed in triplicate), *p=<0.05, Students t-test, inset shows a Western blot of cell lysate probed with anti-ABCG1 anitbodies in which the order of bands corresponds to the order of bars).",
    "ncbi_link": "ABCA12: 74591
ABCG1: 11307"
  },
  {
    "caption": "(L) The effect of overexpression of ABCA1 and ABCG1 on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates assayed in triplicate), *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA1: 11303
ABCA12: 74591
ABCG1: 11307"
  },
  {
    "caption": "(M) The effect of activation of cells with TO901317 (4 μM) on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates assayed in triplicate), *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(N) The effect of overexpression of LXRβ on GSIS from MIN6 cells with ABCA12 deficiency (mean±SEM, n=4 (biological replicates), *p=<0.05, Students t-test, inset shows a Western blot of cell lysates probed with anti-LXRβ antibody in which the order of bands corresponds to the order of bars).",
    "ncbi_link": "ABCA12: 74591
LXRβ: 22260"
  },
  {
    "caption": "(B) Scatter plot and heat map of differential gene expression between cre control and Abca12tm1d mice at 8 weeks of age. Legend indicates Log2 fold change values.",
    "ncbi_link": "Abca12: 74591
cre: 2777477"
  },
  {
    "caption": "(C) Circulating glucose levels after administration of intraperitoneal L-arginine in mice at 8 weeks of age, mean±SEM, n =3 mice per genotype, *p=<0.05 of cre relative to tm1d, Students t-test).",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "(D) Representative images of insulin granule fusion events (yellow circles) in mice of indicated genotypes in response to administration of 15mM glucose (scale bar = 10μm). Quantification of the proportion of responding cells and the density of granule fusion events are presented in graphs in the lower panel (mean±SEM, 8-10 islets/mouse, >4 mice/genotype, **p=<0.01, ***p=<0.001 of cre relative to tm1d, Students t-test).",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "(E) Representative images of insulin granule fusion events (yellow circles) in mice of indicated genotypes in response to administration of 20mM KCl (scale bar = 10μm). Quantification of the proportion of responding cells and the density of granule fusion events are presented in graphs in the right panel (mean±SEM, 8-10 islets/mouse, >4 mice/genotype, **p=<0.01 of cre relative to tm1d, Students t-test).",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "(F) Assessment of calcium flux measured by Fluo4 in response to either Glucose or Potassium in isolated islets from 11 week old animals. Fluorescence responses were corrected for basal fill (F/F0). (mean±SEM, each data point represents the average of 10 cells/coverslip for 13-16 coverslips for each of 4 wild type and 5 Abca12tm1d mice)",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(H) Insulin content of islets of Abca12tm1d mice (mean±SEM, n=3 mice of each genotype, normalised to total protein content).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(A-C) Transmission electron microscopy of β-cells from Abca12tm1d and control mice at 8 weeks of age. Panels A'-C' depict higher resolution images from the boxed regions in A-C (scale bar = 1μm).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(D) Quantitation of the area of 3000 granules from each genotype (mean±SEM, n=4, 3 and 3 animals respectively, *p=<0.05 of cre relative to tm1d, Students t-test). (E) Relative frequency distribution of granule areas from (D). ",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "(G, H) Quantification of change in mean granule area in Abca12tm1d on chow diet and Abca12tm1d on high cholesterol diet islets assessed by transmission electron microscopy (n=3000 granules/genotype, mean±SEM, n=4, 3, 3 and 4 animals respectively, *p=<0.05, Students t-test) as an average and as a relative frequency distribution.",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(J) Glucose tolerance test results following intraperitoneal glucose challenge in Abca12tm1d and cre control mice fed normal chow or HCD (mean±SEM, n=3 mice per genotype, *p=<0.05, for tm1d versus tm1d+HCD, Students t-test).",
    "ncbi_link": "Abca12: 74591
cre: 2777477"
  },
  {
    "caption": "(K) Serum insulin in Abca12tm1d +/- HCD mice after i.p glucose challenge (mean±SEM, n=3 mice/genotype, **p=<0.01, Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(C) Confocal images of rafts (using CTB-Alexa Fluor 647) in MIN6 cells transfected with Fluorescein-488-labelled siRNAScr or Dy547-labelled siRNAABCA12 (scale bar=10μm). (D) Quantitation by confocal microscopy of the effect of ABCA12-deficincy on CTB binding to MIN6 cells (mean±SEM, *p=<0.05, Students t-test, n=4 biological replicates, 50-100 cells for each). (E) Quantitation by flow cytometry of the effect of ABCA12-deficiency on CTB binding to MIN6 cells (mean±SEM, n=3 biological replicates, *p=<0.05, Students t-test). ",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(F) The effect 10 mM MβCD on GSIS in MIN6 cells depleted or not for ABCA12 (incubation for 5 or 10 minutes as indicated, mean±SEM, n=4 (biological replicates), *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(G) Western blot of the abundance of CDC42 in ABCA12 deficient MIN6 cells.",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(H) The effect of ABCA12 deficiency on activation of CDC42 by bradykinin in MIN6 cells (BDK, 100 ng/ml, 4 min; *p=<0.05, Students t-test, significance versus ABCA12-deficient BDK activated cells is indicated, n=4 biological replicates, mean±SEM).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(I,J) (I) Confocal images of F-actin in ABCA12-deficient MIN6 cells (scale bar = 20μm) and (J) quantification of abundance showing the effect of ABCA12-deficiency (mean±SEM, *p=<0.05, Students t-test, n=4 biological replicates, 50-100 cells for each).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(K) F-actin levels assessed by FACS sorting of labelled MIN6 cells transfected with siRNAABCA12 (mean±SEM, n=3 biological replicates, *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA12: 74591"
  },
  {
    "caption": "(L,M) (L) Representative image of F-actin using LifeAct staining of purified islets isolated from Abca12tm1d versus control mice (scale bar = 10μm) and (M) quantitation of fluorescent signals from these samples (n=3 biological replicates, mean±SEM, ***p=<0.001, ****p=<0.0001 Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "O) Effects of overexpression of a constitutively active form of CDC42 on GSIS from MIN6 cells with ABCA12-deficiency (mean±SEM, n=4 biological replicates, *p=<0.05, Students t-test).",
    "ncbi_link": "ABCA12: 74591
CDC42: 12540"
  },
  {
    "caption": "(P) The effect of overexpression of consitutively active CDC42 on ABCA1 abundance in MIN6 cells with ABCA12-deficiency. Treatments are defined in the table below.",
    "ncbi_link": "ABCA12: 74591
CDC42: 12540"
  },
  {
    "caption": "(R) Effects of Abca12 knockdown and Jasplakinolide treatment on MIN6 cell in low and high glucose (mean±SEM, n=4 biological replicates, *p=<0.05, **p=<0.01, significance relative to untreated cells, Students t-test)",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(A) Mass spectroscopy analysis of levels of cholesterol and cholesteryl esters in purified islets from Abca12tm1d mice versus control animals at 16 weeks of age (mean±SEM, n=10, 4 and 5 mice per genotype respectively; COH=cholesterol, CE=cholesteryl ester).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(B) Mass spectroscopy analysis of lipids families in purified islets from Abca12tm1d mice versus control animals at 16 weeks of age (mean±SEM, n=10, 4 and 5 mice per genotype respectively, **p=<0.01 Students t-test); CE=cholesteryl ester, Cer=ceramide, DHC (Hex2Cer)=dihexosylceramide, MHC (HexCer)=monohexosylceramide, SM=sphingomyelin, GM3=GM3 ganglioside, dhCer=dihydroceramide, DG=diacylglyerol, TG=triacylglycerol).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(C) Mass spectroscopy analysis of triglyceride species in purified islets from Abca12tm1d mice versus control animals at 16 weeks of age (mean±SEM, n=10, 4 and 5 mice per genotype respectively, *p=<0.05, **p=<0.01, Students t-test)",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(D) Immunohistochemical staining of levels IL-1β expression in sections of pancreas from Abca12tm1d mice versus control animals at 24 weeks of age (bar = 25μm, islets outlined).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "(E) Quantification of islet specific IL1β staining from sections of Abca12tm1d, Cre and wild type mice (mean±SEM, n=3, 3 and 4 mice of each genotype respectively; *p=<0.05, Students t-test).",
    "ncbi_link": "Abca12: 74591
Cre: 2777477"
  },
  {
    "caption": "Analysis of Abca12tm1d pancreata from mice at 24 weeks of age compared to control mice assessing β-cell mass (F) (I)(mean±SEM, n=3-9 mice per genotype, **p=<0.01, ***p=<0.001, Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "Analysis of Abca12tm1d pancreata from mice at 24 weeks of age compared to control mice assessing cleaved caspase 3 (G) (I)(mean±SEM, n=3-9 mice per genotype, **p=<0.01, ***p=<0.001, Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "Analysis of Abca12tm1d pancreata from mice at 24 weeks of age compared to control mice assessing glucagon (H) (I)(mean±SEM, n=3-9 mice per genotype, **p=<0.01, ***p=<0.001, Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "Analysis of Abca12tm1d pancreata from mice at 24 weeks of age compared to control mice assessing F480+ macrophage populations (I)(mean±SEM, n=3-9 mice per genotype, **p=<0.01, ***p=<0.001, Students t-test).",
    "ncbi_link": "Abca12: 74591"
  },
  {
    "caption": "Heatmaps of AIB1-YAP co-activated, YAP activated, AIB1-YAP corepressed, and YAP repressed genes shown in panel (A). Red and blue indicate high and low levels, respectively. RNA-sequencing was performed in triplicate and statistics in Panel (A-B) were calculated by EdgeR with Benjamini-Hochberg multiple test correction in R.",
    "ncbi_link": "AIB1: 8202
YAP: 10413"
  },
  {
    "caption": "Select genes are regulated by YAP and AIB1, others are YAP regulated independently of AIB1. Endogenous gene expression changes assessed by RT-qPCR.",
    "ncbi_link": "AIB1: 8202
YAP: 10413"
  },
  {
    "caption": "AIB1 modulates TEAD transcriptional activity in a YAP dependent manner. HEK293T cells were transfected with CTGF-promoter reporter and expression vectors of indicated proteins.",
    "ncbi_link": "CTGF: 1490
YAP: 10413"
  },
  {
    "caption": "ANCO1 is recruited to YAP-TEAD by AIB1. Positive Proximity Ligation Assay (PLA) signal (white foci, falsely colored 594nm signal) shown between ANCO1-TEAD, ANCO1-YAP, AIB1-TEAD, and AIB1-YAP, in control cells are lost in AIB1 knockdown. Representative images of Proximity Ligation Assay (PLA) between indicated proteins in MCF10A shGFP (control) and shAIB1 cell lines using antibodies (species) as indicated; Scale bars shown indicate 25μm.",
    "ncbi_link": "GFP: 
AIB1: 8202"
  },
  {
    "caption": "YAP overexpression represses, AIB1 knockdown dysregulates, and ANCO1 knockdown amplifies genes at the 1q21.3 locus in MCF10A and MCFDCIS cells. Gene set enrichment analysis of RNA-seq data and cDNA array data generated from MCF10A cell lines as indicated.",
    "ncbi_link": "ANCO1: 29123
AIB1: 8202
YAP: 10413"
  },
  {
    "caption": "YAP represses 1q21.3 localized genes. Levels of endogenous S100 and SPPR genes in MCF10A cell lines following overexpression of YAP/S94A; levels were assessed by RT-qPCR.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "ANCO1 knockdown increases expression of S100 and SPPR genes in MCF10A and MCFDCIS cells; levels were assessed by RT-qPCR.",
    "ncbi_link": "ANCO1: 29123"
  },
  {
    "caption": "YAP driven suppression of 1q21 genes is reverted upon ANCO1 knockdown. Levels of endogenous 1q21.3 genes were assessed in YAP or S94A-expressing, control or shANCO1 MCF10A cells by RT-qPCR.",
    "ncbi_link": "ANCO1: 29123
YAP: 10413"
  },
  {
    "caption": "ANCO1 is recruited to superenhancers at 1q21.3 by AIB1 and is significantly reduced at 1q21.3 following AIB1 knockdown. ChIP performed with ANCO1 antibodies in control or shAIB1 cells. Levels of precipitated chromatin assessed by qPCR.",
    "ncbi_link": "AIB1: 8202"
  },
  {
    "caption": "YAP driven aberrant sphere formation of MCF10A cell lines is ablated by AIB1 knockdown, but further enhanced by ANCO1 knockdown. Indicated cell lines were plated on Matrigel and allowed to form mammospheres for 7 days. 10x and 40x magnifications shown, Scale bar = 200μm.",
    "ncbi_link": "ANCO1: 29123
AIB1: 8202
YAP: 10413"
  },
  {
    "caption": "Quantification of size (arbitrary units) of aberrant spheres per field displayed in panel (A), relative to control YAP S94A shGFP spheres. n= number of spheres.",
    "ncbi_link": "GFP: 
YAP: 10413"
  },
  {
    "caption": "ANCO1 levels decrease in breast cancer. ANCO1 mRNA expression from normal tissue (GTEX) and Tumor (TCGA) for breast samples.",
    "ncbi_link": "ANCO1: 29123"
  },
  {
    "caption": "A - Distribution of Casp3+ cells in rostral and ventral domains of an E11.5 Rx-Dicer mutant embryo. NCx, neocortex; OB, olfactory bulb; Spt, septum.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "B,C - Marker analysis of Casp3+ cells in the rostral telencephalon of E12.5 Rx-Dicer mutant embryos. Most apoptotic cells are Pax6+ RGCs (solid arrowheads) and not Tbr1+ neurons (open arrowheads). N = 3 replicates per marker.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "D,E - Distribution and abundance of apoptotic cells (Casp3+) in the rostral telencephalic primordium of control and Rx-Dicer mutant embryos at the indicated ages. Dotted line indicates basal surface, dashed line apical surface. N = 3 replicates per genotype and age.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "F,G - Distribution and abundance of mitoses (PH3+) and neurons (Tuj1) in the rostral telencephalic primordium of control and Rx-Dicer mutant embryos at the indicated ages. Dotted line indicates basal surface, dashed line apical surface. N = 3-4 replicates per genotype and age. No significant differences were found between control and mutant embryos in apical nor basal mitoses.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "A - DAPI stain of sagittal sections through the rostral telencephalon of E17.5 control and Rx-Dicer mutant littermates showing the neocortex (NCx) and olfactory bulb (OB; dashed line).",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "B - Expression pattern of Grm1 mRNA in OB (dotted line) of control and Rx-Dicer mutants. C - Quantification of OB perimeter (mean ± SEM; symbols indicate values for individual embryos); t-test, ***P < 0.001. N = 14 replicates per genotype. ",
    "ncbi_link": "Dicer: 192119
Grm1: 14816
Rx: 100125459"
  },
  {
    "caption": "D - Immunostains of E17.5 control and Rx-Dicer mutant brains showing the distribution of progenitor cells (Ki67, red) and neurons (Tuj1, green). Arrowheads indicate rosettes. Sp, septum.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "E - Detail of a rosette from an E17.5 Rx-Dicer mutant embryo displaying typical features: closed apical surface (dotted line) with PH3+ apical mitoses (white arrowhead) and basal mitoses, surrounded by Tuj1+ neurons (green). Dashed line indicates the basal border of the rosette.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "F - Rostral half of an Rx-Dicer mutant E17.5 brain immunostained for Pax6, clarified and segmented to reveal rosettes (yellow). C, caudal; R, rostral.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "G,H - BrdU incorporation and cell cycle re-entry analysis with the progenitor cell marker Ki67 at E17.5, in the rostral cortex of control embryos compared to rostral rosettes of Rx-Dicer mutants. Dotted lines indicate apical surface, dashed lines indicate basal border of VZ. Arrowheads indicate double-positive cells. Data in histograms are mean ± SEM, symbols indicate values for individual embryos; n ≥ 3 embryos; X2-test, *P < 0.05, ***P < 0.001.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "J - Coronal section through the rostral telencephalon of an E14.5 Rx-Dicer mutant embryo illustrating the high abundance and location of rosettes (arrows), as revealed by the distribution of mitoses (PH3) and neurons (Tuj1). K-S - Analysis of the regional identity of rosettes in E14.5 Rx-Dicer mutants. (K) Schema of normal transcription factor expression patterns defining telencephalic regional identity. Expression of Ngn2, Tbr2 and Pax6 identifies rosettes in the rostro-dorsal telencephalon as having dorsal identity (L-N,P); Gsx2, Dlx2 and Dlx5 identify rosettes in the ventral telencephalon as having ventral identity (O,Q); Nkx2.1 identifies MGE rosettes as being normotopic (R); absence of Gsx2 in LGE rosette cells identifies them as ectopic (S). Tuj1 labels neurons. In (L,M), arrowheads indicate the border between dorsal and ventral territories, and dotted line indicates the outer border of the telencephalon. LGE, lateral ganglionic eminence; MGE, medial ganglionic eminence; P, pallium; SP, subpallium. ",
    "ncbi_link": "Dicer: 192119
Dlx2: 13392
Dlx5: 13395
Tbr2: 13813
Gsx2: 14843
Ngn2: 11924
Nkx2.1: 21869
Pax6: 18508
Rx: 100125459"
  },
  {
    "caption": "A - Coronal section through the rostral telencephalon of an E14.5 Rx-Dicer mutant embryo displaying the three types of rosettes.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "B - High magnification of rosettes in Rx-Dicer mutants at E12.5 (Type 1), E14.5 (Type 2) and E17.5 (Type 3), immunostained for PH3 and Tuj1. Dashed line indicates ventricular surface; arrowheads indicate basal mitoses; arrows indicate a stream of apical mitoses connecting the lumen of the rosette with the lumen of the telencephalic ventricle.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "F,G - Distribution of neurons (Tuj1+ cells) and apical adherens junction protein Par3 in the OB primordium of control and Rx-Dicer mutant embryos at the indicated ages. Dotted lines indicate basal border, dashed lines indicate apical border. White arrowheads indicate ectopic neurons and/or absence of Par3. Arrow in (G) indicates accumulation of Par3 at the lumen of a nascent rosette.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "A,B - Changes in expression levels of miRNAs between control and Rx-Dicer mutants at E11.5 in the rostral telencephalon. Red dots indicate statistically differentially expressed miRNAs according to FDR correction of P values based on the Wald statistic (DESeq2 analysis) (B). Dashes lines indicate stringency limits in evaluation of results.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "D,E - Changes in mRNA expression levels between control and Rx-Dicer mutants at E11.5 in the rostral telencephalon. Statistically differentially expressed mRNAs according to FDR correction of P values based on the Wald statistic (DESeq2 analysis; Adj. P < 0.1 and FC > 1.25) are highlighted in red, and the three with the highest Adj. P value are identified by name. Blue dot indicates Irs2: FC=1.748, Adj. P = 5.95e-08.",
    "ncbi_link": "Dicer: 192119
Irs2: 384783
Rx: 100125459"
  },
  {
    "caption": "I,J - ISH stains of Irs2 mRNA, and qPCR for Irs2 mRNA and let-7-5p miRNA, in the rostral telencephalon of control and Rx-Dicer mutant embryos. Dashed line indicates basal border, dotted line indicates apical surface. Arrowheads indicate area with the greatest increase in Irs2 expression. BG, basal ganglia; H, hippocampus; NCx, neocortex; OB, olfactory bulb; Spt, septum. Histograms represent mean ± SEM (logarithmic scale); symbols in plots indicate values for individual embryos; t-test, *P <0.05, **P <0.01. N = 6-9 replicates per group. Scale bar, 100 µm.",
    "ncbi_link": "let-7-5p: 
Dicer: 192119
Irs2: 384783
Rx: 100125459"
  },
  {
    "caption": "A-C - Immunostains for activated p53 (red) in the rostral telencephalon of control and Rx-Dicer mutant embryos at E12.5, and quantification of positive cells (C). Dashed lines indicate apical side, dotted lines indicate basal side. N = 4 replicates per genotype. Scale bar, 50µm.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459"
  },
  {
    "caption": "M-O - Sagittal sections through the rostral telencephalon of E17.5 embryos of the indicated genotypes. Note the rosettes and general disorganization in Rx-Dicer single mutants, and complete rescue of this phenotype in Rx-Dicer-p53 double mutants. NCx, neocortex; OB, olfactory bulb. Scale bar, 1 mm.",
    "ncbi_link": "Dicer: 192119
Rx: 100125459
p53: 22059"
  },
  {
    "caption": "A - Relative Irs2 mRNA levels in HEK cells upon transfection with Gfp- or Irs2-encoding plasmids. Mean ± SEM; t-test, ****P < 0.0001. N = 6 replicates per group.",
    "ncbi_link": "Gfp: 
Irs2: 384783"
  },
  {
    "caption": "B-D - Distribution of neurons (Tuj1, red), GFP (green) and mitoses (PH3, white) in the rostral telencephalon of wild-type E14.5 or E17.5 mouse embryos, as indicated, electroporated at E12.5 with the indicated plasmid combinations. Dashed line indicates the apical surface. Insets show the same field of view, with location and extent of electroporations. Note the overlap of rosettes (arrows) with ectopic neurons at the apical surface (arrowheads) and increased basal mitoses, upon overexpression of Irs2 (C). Asterisk indicates absence of malformation in nearby cortex. At E17.5 (D) GFP+ rosettes remain in deep cortical layers (arrowheads).",
    "ncbi_link": "Irs2: 384783"
  },
  {
    "caption": "I-M - Distribution of neurons (Tuj1, red), GFP (green) and mitotic (PH3, white) or apoptotic (Casp3, white) cells in the rostral telencephalon of wild-type E13.5 embryos electroporated at E12.5 with the indicated plasmids, and quantification of Casp3+ cells (M). Dashed line indicates apical surface, dotted lines indicate borders of the cortical plate (CP). Nascent rosettes (arrows) are next to ectopic ventricular neurons (arrowheads in K') and basal mitoses, without significant apoptosis in VZ (L',M). Mean ± SEM; t-test; ns, not significant, *P < 0.05. N = 3-6 replicates per group. N - Distribution of neurons (Tuj1, red) in the rostral telencephalon of wild-type E14.5 embryos electroporated at E12.5 with a combination of plasmids encoding Irs2, let-7a, let-7b and let-7c, and Gfp. Dashed line indicates apical surface. Formation of rosettes in Irs2-expressing embryos is rescued by overexpression of let-7. Inset shows the same field of view, with location and extent of electroporation. ",
    "ncbi_link": "Irs2: 384783
let-7a: 723965///387244
let-7b: 387245
let-7c: 723966
let-7: 723966///387246///387245///723965///387244"
  },
  {
    "caption": "B-G - Distribution of neurons (Tuj1, red), GFP (green) and mitoses (PH3, white) in the rostral telencephalon of wild-type E14.5 mouse embryos electroporated at E12.5 with the indicated plasmid combinations. Inset shows the same field of view, with location and extent of electroporations. In (C) and (E), arrows indicate rosettes and arrowheads indicate neuronal ventricular ectopias. (D) and (F) are high magnification details of individual rosettes (dashed lines), where arrowheads indicate apical and basal mitoses. Loss of endogenous let-7 drives the formation of rosettes and ventricular neuronal ectopias (C), which is rescued with the additional loss of Irs2 (G).",
    "ncbi_link": "Irs2: 384783
let-7: 723966///387246///387245///723965///387244"
  },
  {
    "caption": "(D) Regulatory modes of representative VxrB-controlled genes in response to PenG. Upper plot shows VxrB binding patterns (assessed via ChIP-Seq), lower panel shows transcriptional response upon overexpression of VxrB D78E (assessed via RNA-Seq). RNA expression was confirmed by S1 nuclease mapping assay in wild type and ΔvxrAB mutant strains after exposure to PenG (100 µg/ml for 3 hours). White demarcation line between time points indicates that these data points were not adjacent in the original experiment but were cropped for presentation purposes. Source data is available as supplemental material.",
    "ncbi_link": "VxrB: "
  },
  {
    "caption": "Reduction of cell wall synthesis gene expression causes a tolerance defect. (C) Survival of a ∆pbp1b ∆pbp1a Piptg:pbp1a strain after 6 hours of PenG exposure. Pup indicates conditions of high IPTG concentrations (100 µM), Pdown low IPTG concentration (2 µM). Survival fraction is cfu/ml of PenG-treated cultures normalized to untreated cultures grown in and plated on medium containing the same IPTG concentration.",
    "ncbi_link": "pbp1a: "
  },
  {
    "caption": "(C) Time-course of iron accumulation in PenG-treated WT and ∆vxrAB cells as measured by ICP-MS. Data are average of 3 independent biological replicates, error bars represent standard deviation. ∗∗P=0.001; ∗∗∗P<0.0003 (paired t-test).",
    "ncbi_link": "vxrA: "
  },
  {
    "caption": "(B). To test PenG-mediated induction of Fur-regulated genes, S1 nuclease mapping assays were performed on the small RNA ryhB, the RyhB target sodB, hutA/B, coding for heme transport systems and vc2212, which encodes a component of a ferric citrate uptake system). Cells were grown to mid-exponential phase followed by exposure to H2O2 or PenG for the indicated duration. Numbers represent expression levels normalized to untreated control (averages from three independent replicates). White demarcation line between time points indicates that these data points were not adjacent in the original experiment but were cropped for presentation purposes. Source data is available as supplemental material.",
    "ncbi_link": "hutA: 
vc2212: 
Fur: 57740727
ryhB: RF00057
RyhB: RF00057
sodB: 57740672"
  },
  {
    "caption": "(B) and (C) Iron uptake mutants restore ∆vxrAB growth on 10% sucrose. The indicated strains were grown to exponential phase (OD600~0.5) in LB medium and spot-plated on 10% Sucrose plates with or without additional iron sulfate. An example is shown in (B), quantification of cfu is shown in (C). Data information: Data are average of 3 independent biological replicates, error bars represent standard deviation. ∗∗∗ P<0.0003; ∗∗∗∗ P<0.0001 (paired t-test).",
    "ncbi_link": "vxrA: "
  },
  {
    "caption": "(E) Time-dependent killing of respiratory chain mutants (∆nqrA, encoding NADH dehydrogenase and ∆ubiA, encoding an early step of ubiquinone synthesis) in the presence of PenG (100 µg/ml, 10xMIC). All strains were grown in LB 0.2 % glucose. Data information: Data are mean of three independent biological replicates and error bars represent standard deviation.",
    "ncbi_link": "nqrA: 
ubiA: 57741401"
  },
  {
    "caption": "(F) Growth-phase dependent killing assay of ROS detoxification systems (∆fur, ∆sodB, and ∆oxyR1∆katG∆katB). At designated time-points, a 5 ml aliquot was withdrawn and exposed to 100 µg/ml PenG for 3 h. CFU/mL for each time point was assessed before (solid lines) and after addition of PenG (dotted lines). Data information: Data are mean of three independent biological replicates and error bars represent standard deviation.",
    "ncbi_link": "katB: 
oxyR1: 
fur: 57740727
katG: 57740217
sodB: 57740672"
  },
  {
    "caption": "(I-L) Control and IRGM knockdown THP-1 IFN reporter cells were treated with (I) Poly I:C (1 μg/ml) for 8 h, 12 h and 24 h or (J) Poly dA:dT (1 μg/ml) for 12 h and 24 h or (K) IFN-β (500 ng/ml) for 8 h and 12 h or (L) cGAMP (1 μg/ml) for 12 h and 24 h and the supernatant was subjected to luciferase reporter assay using QuantiLuc reagent",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(M-P) Control and IRGM knockdown THP-1 cells were untreated and treated with Poly I:C (1 μg/ml) for 8 h and the total RNA was subjected to qRT PCR with primers of (M) MX2 (N) ISG15 (O) OAS1 and (P) IFN-β. (Q-T) Control and IRGM knockdown THP-1 cells were untreated and treated with Poly dA:dT (1 μg/ml) for 8 h and the total RNA was subjected to qRT PCR with primers of (Q) MX2 (R) ISG15 (S) OAS1 and (T) IFN-β.",
    "ncbi_link": "IRGM: 345611
ISG15: 9636
MX2: 4600
OAS1: 4938
IFN-β: 7157"
  },
  {
    "caption": "(D) RNA was isolated from irgm1+/+ and irgm1-/- BMDMs and subjected to qRT-PCR with indicated viral restriction factor genes",
    "ncbi_link": "irgm1: 15944"
  },
  {
    "caption": "(H-J) RNA isolated from control and IRGM knockdown HT-29 cells and subjected to qRT-PCR with indicated genes of (H) Immunoproteasome complex (I) TAP complex (J) human leukocyte antigen (HLA) system.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(L, M) Antigen processing assay shown by representative confocal images of control and IRGM siRNA transfected THP-1 cells treated with DQ-OVA (green) (10 µg/ml, 30 min). Scale Bar, 10 µm. (M) Graph depicts percentage of control and IRGM knockdown THP-1 cells with DQ-OVA puncta's",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(P) Representative confocal images of H-2Kb-SIINFEKL (red) on the surface of Irgm1+/+ and irgm1-/- mouse BMDMs treated with OVA (2 mg/ml, 3 h), Scale bar 5 µm or 8 µm (as indicated).",
    "ncbi_link": "Irgm1: 15944
irgm1: 15944"
  },
  {
    "caption": "(C) Representative images of the plaque assay in Vero cells performed from the culture supernatant of CHIKV (MOI 1, 24 h) infected HT-29 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(F) Representative images of plaque assay in Vero cells performed from the culture supernatant of HSV-1 (MOI 1, 24 h) infected HT-29 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(I) Representative images of plaque assay in Vero cells performed from the culture supernatant of JEV (MOI 1, 24 h) infected HT-29 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(L) Representative images of plaque assay in Vero cells were performed from the culture supernatant of WNV (MOI 0.3, 16 h) infected HuH7 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(O) Representative images of plaque assay in Vero cells were performed from the culture supernatant of ZIKV (MOI 5, 48 h) infected Huh7 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(S) Representative images of plaque assay in Vero E6 cells were performed from the culture supernatant of SARS-CoV2 (MOI 1, 24 h) infected THP-1 control and IRGM knockdown cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(D) Kaplan-Meier survival graph depicts percentage survival of mock and CHIKV infected irgm1+/+ and irgm1-/- neonates during the course of infection",
    "ncbi_link": "irgm1: 15944"
  },
  {
    "caption": "(H, I) Total RNA isolated from muscles and brains of mock and CHIKV infected (MOI 1x107 PFU/mouse) (6 dpi) irgm1+/+ and irgm1-/-mice and was subjected to qRT PCR with MX2 The total RNA used for qRT PCR with the brain is four times more than muscles.",
    "ncbi_link": "irgm1: 15944
MX2: 17858"
  },
  {
    "caption": "(A-D) Control and si-IRGM transfected THP-1 IFN reporter cells were kept uninfected (Mock) or infected with (A) JEV (MOI 5) or (B) CHIKV (MOI 5) or (C) HSV-1 (MOI 2.5) or (D) VSV-eGFP (MOI 1) and the supernatant collected 8 hpi were subjected to luciferase assay. The graphs depict fold change in interferon response.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(L) Western blot analysis with cell lysates of mock and CHIKV (MOI 5, 24 h) infected control and IRGM knockdown HT-29 cells and probed with the indicated antibodies. (M) Western blot analysis with cell lysates of mock and JEV (MOI 5, 24 h) infected control and si-IRGM transfected HT-29 cells and probed with the indicated antibodies. ",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(Q) Western blot analysis with cell lysates of mock and CHIKV (MOI 1, 24 h) infected control and IRGM knockdown HT-29 cells transfected with indicated siRNA and probed with the indicated antibodies.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Confirmation of decreased mitochondrial proteins in WT but not in FIP200 ko cells expressing CID Nix either untreated or treated for 24 hours with Rapalog by immunoblotting. Quantification of MTCO2 relative to Actin over three independent experiments after treatment with Rapalog over 24 hours by immunoblotting. Cells in this figure express mtKeima-P2A-FRB-Fis1tTand EGFP-Nix1-188-FKBP. Data Information: Area shading indicates standard deviation between wells. Over one thousand cells quantified per condition. Statistics performed by two-way ANOVA; ** indicates a p-value<0.01, *** indicates a p-value<0.001. Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
Keima: 
Nix: 665
Fis1: 51024
FKBP: 2280
FIP200: 9821"
  },
  {
    "caption": "Mitophagy time course by mtKeima of different Nix truncation mutants recruited with CID, measured by percentage of Keima positive pixels above threshold. Data Information: Area shading indicates standard deviation between wells. Over one thousand cells quantified per condition. Experiments repeated at least 3 times.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "Mitophagy by mtKeima of Nix1-70 when treated with Torin, Rapalog, or both compared to control. Mitophagy by mtKeima of Nix1-87 when treated with Torin, Rapalog, or both compared to control. Data Information: Area shading indicates standard deviation between wells. Over one thousand cells quantified per condition. Experiments repeated at least 3 times.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "HeLa cells expressing FKBP-EGFP- p62327-348 or FKBP-EGFP-WIPI2b were treated for 16 hours with phenanthroline to induce endogenous Nix and BNIP3 expression, then underwent a GFP-pulldown and compared to 1% input by immunoblot. Data Information IP Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
FKBP: 2280
p62: 8878
WIPI2b: 26100"
  },
  {
    "caption": "IP western blot of FKBP-EGFP-Nix1-188 compared to Nix60-188, comparing 1% input to GFP-pulldown and blotted against GFP or WIPI2 after 4 hours of Rapalog. Data Information IP Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
Nix: 665
FKBP: 2280"
  },
  {
    "caption": "Representative images of WT or WIPI2 ko HeLa cells expressing EGFP-Nix1-188-FKBP (green), mtKeima, and FRB-Fis1T with or without 4 hours of Rapalog immunostained for endogenous Tom20 (red) and GABARAP (white). Scale bar: 50µm. Automated puncta counting of GABARAP in WT or WIPI2 ko cells normalized to cell number in control conditions or after 4 hours with Rapalog. Data Information: Error bars indicate standard deviation. Statistics performed by two-way ANOVA; ** indicates a p-value<0.01, *** indicates a p-value<0.001. ns indicates not significant. Over one thousand cells quantified per condition. Experiments repeated at least 3 times.",
    "ncbi_link": "WIPI2: 26100"
  },
  {
    "caption": "GFP pulldown of EGFP-Nix1-188-FKBP in WT, WIPI2 ko, or FIP200 ko cells after 4 hours of Rapalog treatment. FIP200 cropped due to the appearance of non-specific bands after IP. Data Information: Error bars indicate standard deviation. Statistics performed by two-way ANOVA; ** indicates a p-value<0.01, *** indicates a p-value<0.001. ns indicates not significant. Over one thousand cells quantified per condition. Experiments repeated at least 3 times.",
    "ncbi_link": "FIP200: 9821
WIPI2: 26100"
  },
  {
    "caption": "Automated puncta counting of endogenous Halo -WIPI2 in U2OS cells expressing either FKBP-EGFP-Nix1-87 (LIR and MER), Nix60-188 (MER), or Nix1-70 (LIR) after 16 hours of Rapalog treatment then fixed. Data Information: Error bars indicate standard deviation between wells. Over one thousand cells quantified per condition. Statistics performed by two-way ANOVA;* indicates a p-value<0.05, ** indicates a p-value<0.01, **** indicates a p-value<0.0001. ns indicates not significant. Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
Nix: 665
FKBP: 2280"
  },
  {
    "caption": "Percent cells above threshold line shown in panel A as indication of mitophagy measured by mtKeima after one week of stably expressing EGFP, or EGFP-Nix as WT or with W36A/L39A or L75A mutations. Data Information: Error bars indicate standard deviation between wells. Over one thousand cells quantified per condition. Statistics: Panel B - two-tailed unpaired student's t-test ** indicates a p-value<0.01, **** indicates a p-value<0.0001. ns indicates not significant. Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
Nix: 665"
  },
  {
    "caption": "Automated puncta counting of endogenous Halo -WIPI2 in U2OS cells expressing FKBP-EGFP-Nix1-188 as WT or with W36A/L39 (LIR) or L75A (MER) mutations after 16 hours of Rapalog treatment then fixed. Data Information: Error bars indicate standard deviation between wells. Over one thousand cells quantified per condition. Statistics: panels C two-way ANOVA; ** indicates a p-value<0.01, **** indicates a p-value<0.0001. ns indicates not significant. Experiments repeated at least 3 times.",
    "ncbi_link": "EGFP: 
Nix: 665
FKBP: 2280"
  },
  {
    "caption": "GFP pulldown of EGFP alone, EGFP-Nix1-188-FKBP as WT, W36A/L39A, or L75A mutants after 4 hours of Rapalog treatment.",
    "ncbi_link": "EGFP: 
Nix: 665
FKBP: 2280"
  },
  {
    "caption": "F Activities of TFF3, FABP1, MKI67 and MMP7 in organoid single cell transcriptomes, ordered along latent time.",
    "ncbi_link": "FABP1: 2168
MKI67: 4288
MMP7: 4316
TFF3: 7033"
  },
  {
    "caption": "A Gene expression of LGR5 and EPHB2, along activity gradients of LGR5-ISC or MAPK target gene signatures.",
    "ncbi_link": "EPHB2: 2048
LGR5: 8549"
  },
  {
    "caption": "A Normalized firefly luciferase luminescence (compared to renilla luciferase) as a function of external IAA concentration. Arabidopsis protoplast cells were transiently transformed with either AtPIN1 or GFP (in the case of the control) both under the control of a constitutive CaMV 35S promoter. Where indicated, 10 µM NPA was added. B Normalized firefly luciferase luminescence (compared to renilla luciferase) as a function of external NPA concentration in the presence of 100nM IAA in control GFP- (blue or red) or PIN1- (green or purple) transformed protoplasts. ",
    "ncbi_link": "35S: 
GFP: 
PIN1: 843693"
  },
  {
    "caption": "b) Fourteen-day-old Arabidopsis seedlings (wild type, brown; pPIN1::Mab9B2; blue) grown on AM containing 0.2 µM NPA. Scale bar = 1 cm.",
    "ncbi_link": "Mab9B2: 
PIN1: 843693"
  },
  {
    "caption": "c) NPA-affected lateral root density of nine-day-old Arabidopsis seedlings expressing Mab9B2 scFv fragments (wild type sample sizes were between 16 and 21 plants; Mab9B2 sample sizes were between 12 and 31 plants). Bars indicate standard error.",
    "ncbi_link": "Mab9B2: "
  },
  {
    "caption": "d) NPA-affected apical hook angle in dark-grown three-day-old Arabidopsis seedlings expressing Mab9B2 scFv fragments. (wild type sample sizes were between 38 and 50 plants; Mab9B2 sample sizes were between 33 and 45 plants). e) Gravitropic curvature in four-day old Arabidopsis seedlings expressing Mab9B2 scFv fragments. (wild type sample sizes were between 15 and 21 plants; Mab9B2 sample sizes were between 14 and 20 plants).",
    "ncbi_link": "Mab9B2: "
  },
  {
    "caption": "D) Cells expressing empty vector (EV), or PRKAA1-myc, PRKAB2 and PRKAG2-FLAG (AMPK) alone or with myc-Ulk1 WT (ULK) were cultured in full medium (F), EBSS (St), or serum-free medium (SFM) alone or in the presence of 991 (1µM) or MRT68921 (1μM) for 90 minutes as indicated. 2% Loading control and pull down samples were analysed by Western blot.",
    "ncbi_link": "AMPK: 5562
Ulk1: 22241"
  },
  {
    "caption": "A) VPS15-ZZ was co-expressed with Ulk1 and Ulk2 wild type (WT) or kinase inactive (KI) before analysis by Western blot. An electrophoretic mobility shift in VPS15-ZZ was noted with WT only.",
    "ncbi_link": "VPS15-ZZ: 30849
Ulk1: 8408
Ulk2: 9706"
  },
  {
    "caption": "A) Lysates from 3 control clones and 7 VPS15 CRISPR clones were analysed by Western blot. LC3 and p62 accumulation as well as depletion of VPS34 CI components was observed in all 6 sgA-derived clones.",
    "ncbi_link": "CRISPR: 
VPS15: 30849"
  },
  {
    "caption": "B) Controls and 6 VPS15 CRISPR KO clones were starved for 1 hr, fixed and imaged for WIPI2 (green). Depletion of VPS15 was associated with a block in WIPI2 puncta formation and large vacuoles (red asterisks). Quantification of WIPI2 spots, mean +/- SEM, n=3.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "D) Wild type (WT), 6SA or 6SE VPS15-HA, or empty vector (EV), were expressed in VPS15 KO or HEK293A cells. Cells were starved for 1 hr and the distributions of WIPI2 (green), HA (red) and LC3 (blue) were assessed, mean +/- SEM, n=4.",
    "ncbi_link": "VPS15: 30849"
  },
  {
    "caption": "D) VPS34 CI components expressed with Ulk1 1-427 WT or KI as indicated. After starvation for 1 hr in the presence or absence of MRT68921 (ULK inhibitor), cells were lysed and VPS34 CI coimmunoprecipitated via ATG14-ZZ. VPS15 S861 phosphorylation was increased in the presence of active Ulk1. VPS15 pS861/total VPS15 was quantified, mean +/- SEM, n=3.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "E) HEK293A were transfected with VPS34 CII components and Ulk1 1-427 WT or KI and treated as indicated before VPS34 CII co-immunopurification via UVRAG-ZZ. Samples were analysed by Western blot as in D, revealing that Ulk1 can similarly phosphorylate VPS15 at S861 when incorporated into CII. Quantifications show mean of 4 independent experiments +/-SEM, ***p<0.001 [one-tailed ANOVA].",
    "ncbi_link": "VPS34: 5289
Ulk1: 22241"
  },
  {
    "caption": "A) HEK293A, VPS15 KO control and stably rescued VPS15 KOs (sgA-B3) were starved for 1 hr before WIPI2 (green), LC3 (red) and DNA (Hoechst, blue) were visualised. Quantification of WIPI2 puncta number per cell, mean +/-SEM, n=5.",
    "ncbi_link": "VPS15: 30849"
  },
  {
    "caption": "B) Stably rescued VPS15 KO (sgA-B3), HEK293A and VPS15 KO control cells were starved for 1 hr with (SB) or without (St) 100nM Bafilomycin A1, or cultured in full media (F). Quantification shows LC3II/Actin, mean +/-SEM, n=5.",
    "ncbi_link": "VPS15: 30849"
  },
  {
    "caption": "A) HEK293A were treated with VPS34-IN1 (1μM) alone or in the presence of MRT68921 (1μM) for the indicated time. Untreated VPS15 KOs were included as a positive control and lysates analysed by Western blot. Identical samples were loaded in parallel for VPS34, ATG13, PRKAB2 analysis, indicated by dashed line.",
    "ncbi_link": "VPS15: 30849"
  },
  {
    "caption": "E) HEK293A and VPS15 KO cells were fed, or starved for 2 hrs before fixation, and labelling with ULK1 (green), ATG9A (red) and GM130 (blue). Dashed boxes show magnified regions of interest.",
    "ncbi_link": "VPS15: 30849"
  },
  {
    "caption": "B) HEK293A were transfected with siRNAs targeting ATG14, UVRAG or p62, or with non-targeting siRNA (RISC-free, RF) and cells were treated with VPS34-IN1 (IN1; 1μM) for 0, 4 or 18 hrs as indicated. Quantification of ATG13 pS318/Total ATG13, mean +/- SEM, n=3. Identical samples were loaded onto 2 separate SDS PAGE gels for Western blot analysis, indicated by dashed line.",
    "ncbi_link": "ATG14: 22863
p62: 8878
UVRAG: 7405"
  },
  {
    "caption": "C) Cells transfected as in B were treated with IN1 for 18 hours as indicated, fixed and labelled for ubiquitin (green), FIP200 (red) and p62 (blue). FIP200-positive bodies were quantified from 4 independent experiments with mean +/- SEM plotted. Cells transfected with ATG14 siRNA generated significantly more FIP200 bodies per cell than all other conditions tested.",
    "ncbi_link": "ATG14: 22863"
  },
  {
    "caption": "Whole-mount immunofluorescence of anti-6mA in 64-128-cell embryos upon injection of shGFP (as control), shAlkbh1",
    "ncbi_link": "GFP: 
Alkbh1: 130621774"
  },
  {
    "caption": "Relative quantification of anti-6mA signals from immunofluorescence images Fluorescence intensity were normalized to the highest and lowest measured area in shGFP (n=135), shAlkbh1 (n=168), and rescue (n=140), where n = nuclei numbers. Central band shows the mean, the boxes show lower and upper quartiles and whiskers show minimum and maximum data values.",
    "ncbi_link": "GFP: 
Alkbh1: 130621774"
  },
  {
    "caption": "Quantification of shAlkbh1-electroporated embryos showing significantly higher level of 6mA/dA (P<0.05) compared to shGFP electroporated embryos and to wild type embryos at 64-128 cell stage.",
    "ncbi_link": "GFP: 
Alkbh1: 130621774"
  },
  {
    "caption": "Whole-mount image of EU incorporation signals at 64 cells upon injection with shGFP, shAlkbh1, rescue, and mutant-rescue solution Relative quantification of EU signals Fluorescence intensity were normalized to the highest and lowest measured area in shGFP (n=86), shAlkbh1 (n=63), rescue (n=64), and mutant-rescue (n=66) where n = nuclei numbers. Central band shows the mean, the boxes show lower and upper quartiles and whiskers show minimum and maximum data values.",
    "ncbi_link": "GFP: 
Alkbh1: 130621774"
  },
  {
    "caption": "(A) MOG1 interacts genetically with the H2B deubiquitination machinery. Ten-fold serial dilutions of the indicated strains were spotted on YPD and incubated for 2 days at the indicated temperatures",
    "ncbi_link": "MOG1: 853537"
  },
  {
    "caption": "(B) Expression levels of total H2B and H2Bub1 were analyzed in wild-type (WT), mog1Δ, ubp8Δ and ubp8Δmog1Δ whole cell lysates by western blotting using anti-total H2B and anti-H2Bub1 antibodies. Bar graphs of H2Bub1 levels after H2B normalization show the mean and standard deviations of at least three independent experiments. The P-value was calculated using Student´s t-test. Error bars represent SD. The P-value was calculated using Student´s t-test (*, P = 0.01-0.05; **, P = 0.001-0.01; ***, P < 0.001)",
    "ncbi_link": "mog1: 853537
ubp8: 855263"
  },
  {
    "caption": "(A) The expression levels of H3K4me3 and H3 in total extracts of wild-type (WT), mog1Δ, set1Δ and spp1Δ strains were analyzed by western blotting using the indicated antibodies. Bar graphs of H3K4me3 levels after H3 normalization show the mean and standard deviations of at least three independent experiments. The P-value was calculated using Student´s t-test (*, P = 0.01-0.05; **, P = 0.001-0.01; ***, P < 0.001)",
    "ncbi_link": "mog1: 853537
set1: 856519
spp1: 855965"
  },
  {
    "caption": "(B) ChIP analysis of H3K4me3 presence at ADH1, PMA1 and YEF3 promoter (P) and 5'ORF in wild-type (WT) or mog1Δ strains relative to total H3. The bar graphs indicate the mean and standard deviation for at least three independent experiments. The significance of the differences was calculated using Student´s t-test (*, P value = 0.01-0.05; **, P value = 0.001-0.01; ***, P < 0.001)",
    "ncbi_link": "H3: 
ADH1: 854068
mog1: 853537
PMA1: 852876
YEF3: 850951"
  },
  {
    "caption": "(C) MOG1 interacts genetically with the H3 methylases Set1 and Set2. Ten-fold serial dilutions of the indicated strains were spotted on YPD and incubated for 2 days at the indicated temperatures. (D) histone H3K4A and H3K4Amog1Δ strains were compared with their isogenic strains as in (C)",
    "ncbi_link": "H3: 
MOG1: 853537
mog1: 853537
Set1: 856519
Set2: 853271"
  },
  {
    "caption": "(B) mRNA synthesis rates (SR) as determined in Genomic Run-On analysis and (C) mRNA abundance (RA), in mog1∆ compared with wild type (WT) cells. Bar graphs showing the average level and standard deviation of three experiments (n=3) for SR and RA values obtained as the median of the whole gene dataset values in arbitrary units (x 107) from image analysis quantification. Error bars represent SD. Significance of the differences was obtained using Student´s t-test and statistical difference is considered as *, P value = 0.01-0.05; **, P value = 0.001-0.01; ***, P value < 0.001. The scatter plots (right panels) show the variation of the transcription (B) or mRNA (C) levels of individual genes. Pearson correlation values are: -0.039 (SR) and -0.042 (RA). This low correlation and the flat shape of the clouds on scatter plots (see red tendency line) indicates that there is no bias of the transcriptional effect with regard to expression level. (D) Box plots of SR and RA median levels of mog1Δ cells compared with WT for all genes (Total), SAGA and TFIID-dominated genes. These data were obtained from three independent replicates (n=3) of the RA and SR data that were averaged as explained in the main text. The median and standard deviation for the whole data set (Total) and for 351 (for RA) or 316 (SR) SAGA-dominated genes and for the 3903 (RA) or 3403 (SR) TFIID-dominated genes are shown. Significance of the differences was calculated using Student´s t-test. No significant difference between the different groups was found. The similar variations in SRs and RAs indicate that there are no changes in mRNA half-lives upon MOG1 deletion (shown in Fig EV4). The total number of genes with confident value in the analyses was 3953 for RA and 3989 for SR",
    "ncbi_link": "mog1: 853537
MOG1: 853537"
  },
  {
    "caption": "(A) ChIP analysis of TAP-tagged Rad6 presence at ADH1, PMA1 and YEF3 coding regions (5' & 3') in WT or mog1Δ strains. Bar charts indicate the mean and standard deviation for at least three independent experiments. Significance of the differences was obtained using Student´s t-test (*, P value = 0.01-0.05; **, P value = 0.001-0.01, ***, P value = 0.0001-0.001, ****, P value <0.0001). (B), (C) and (D) Bre1-TAP, Rtf1-TAP and Rpb3 respectively, were analyzed as described in (A). (E) Bar charts showing the relative chromatin occupancy to 5'ORFs (left panel) or 3'ORFs (right panel) of each factor relative to Rpb3 occupancy at these gene positions.",
    "ncbi_link": "ADH1: 854068
mog1: 853537
PMA1: 852876
YEF3: 850951"
  },
  {
    "caption": "(A) Co-purification of Rtf1-PK in cells expressing Mog1-TAP (+,+). A non-tagged strain (-,-) and cells expressing only Rtf1-PK (+,-) were included as negative controls for co-purification. Inputs and IPs are depicted for each strain.",
    "ncbi_link": "Mog1: 853537
Rtf1: 852607"
  },
  {
    "caption": "(B) ChIP analysis of the presence of HA-tagged Mog1 compared to a non-tagged strain (WT) at PMA1 and YEF3 promoter (P) and coding regions (5'ORF). The occupancy level was calculated as the signal ratio of the IP samples in relation to the Input signal normalized to an Intergenic region. Bar charts indicate the mean and standard deviation for at least three independent experiments. Significance of the differences was obtained using Student´s t-test and is presented as a P-value (*, P<0.05).",
    "ncbi_link": "PMA1: 852876
YEF3: 850951"
  },
  {
    "caption": "(D) Mog1-HA immunoprecipitation in cells expressing Bre1-PK (upper panel) and Mog1-TAP co-precipitation in cells expressing Ada2-HA (lower panel) are indicate as in (A) Inputs and IPs are depicted for each strain.",
    "ncbi_link": "Bre1: 851485
Mog1: 853537"
  },
  {
    "caption": "(A) The Mog1E65K Ran-binding mutant complements the slow growth of mog1ΔsetΔ mutants. Ten-fold serial dilutions of wild-type (WT), mog1Δ, set1Δ, and mog1ΔsetΔ strains transformed with wild-type MOG1 (pMOG1) or with the Ran-binding mutant (pMOG1E65K) as indicated were spotted on SC-LEU and incubated for 2 days at the indicated temperatures.",
    "ncbi_link": "mog1: 853537
MOG1: 853537
Mog1: 853537
set1: 856519
set: 853271///856519"
  },
  {
    "caption": "(B) The Mog1E65K Ran-binding mutant complements the low H3K4me3 and H2Bub1 levels of mog1Δ. The expression levels of H3K4me3, total H3, H2Bub1, total H2B and PGK1 in whole cell lysates from wild type (WT) or from mog1Δ cells transformed with an empty plasmid (+pEmpty), wild type MOG1 (pMOG1) or a Ran-binding mutant (pMOG1E65K) were analyzed by western blotting using the corresponding antibodies.",
    "ncbi_link": "MOG1: 853537
Mog1: 853537
mog1: 853537"
  },
  {
    "caption": "(C) Gsp2 is not involved in H2Bub1 regulation. The expression levels of total H2B and of H2Bub1 were analyzed in whole cell lysates from wild type (WT) and gsp2Δ strains by western blotting using anti-total H2B and anti-H2Bub1 antibodies.",
    "ncbi_link": "gsp2: 854357"
  },
  {
    "caption": "The VPR and DPR (right) were dissected from E10.5 Pdx1-GFP embryos (left). Scale bar: 500 µm. DPR, dorsal Pdx1-expressing region; VPR, ventral Pdx1-expressing region; Duo, duodenum bud.",
    "ncbi_link": "GFP: 
Pdx1: 18609"
  },
  {
    "caption": "The ratios of GFPhigh cells to GFP+ cells in the VPR and DPR. The data show the mean ± SEM; n = number of independent biological replicates, unpaired t-test. ***p-value < 0.001.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Hierarchical clustering of 815 genes correlating with the first two PCs identified three groups of cell types and four major distinct clusters (a-d) of genes (p < 1 ×10-9, cell cycle-related genes are excluded). Each column is a single-cell, and each row represents one gene. Cluster-specific TFs are listed on the right. The genes in bold are known to have roles in pancreatic development. L, GFPlow; H, GFPhigh.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Flow cytometric analysis of endocrine progenitors and β-cells in the ventral pancreases (V. P.) and dorsal pancreases (D. P.). (A, D and G) Dissected ventral and dorsal pancreatic tissues. Scale bar: 500 µm. (B, E and H) FACS gating for sorting Ngn3-GFP+ or Ins1-RFP+ cells from the V. P. and D. P. (C and F) statistical analysis of percentages of Ngn3-GFPhigh cells among Ngn3-GFP+ cells in the V. P. and D. P. (I) Statistical analysis of percentages of Ins1-RFP+ cells among total pancreatic cells in the V. P. and D. P.",
    "ncbi_link": "GFP: 
Ngn3: 11925"
  },
  {
    "caption": "Pdx1 and Sox17 expression levels in E9.5 VPR and DPR cells.",
    "ncbi_link": "Pdx1: 18609
Sox17: 20671"
  },
  {
    "caption": "Sagittal section of E12.5 Pdx1-Cre; Rosa26-LacZ mouse embryo counterstained for ALB (brown). X-gal staining (blue) showing cells derived from Pdx1-expressing cells. The arrowheads indicate cells co-stained with X-gal and ALB (See Fig EV5D for more images of different sections). Scale bar: 50 µm (left) or 20 µm (right).",
    "ncbi_link": "Rosa26: 
LacZ: 
Cre: 2777477
Pdx1: 18609"
  },
  {
    "caption": "C: qPCR validation to test different ERK signal durations. HEK293∆RAF1:ER cells were treated with 4OHT and U0126 for different periods of time to generate signal duration scenarios of 0.5 to 8 hours (cf. Fig EV1 C). mRNAs of IEGs EGR1 and FOS relay signal duration to response duration, whereas ILGs CLU and FOSL1 decode signal duration to response amplitude (qPCR data for all 17 validated mRNAs is shown in Fig EV6 A).",
    "ncbi_link": "CLU: 1191
EGR1: 1958
FOS: 2353
FOSL1: 8061"
  },
  {
    "caption": "Immunofluorescent analysis showing fluorescence intensity of phosphorylated TDP-43 (pTDP-43). Scale bar: 20µm. Presented immunofluorescent images of control (C2) and mutant TDP-43 (P2). I represents its corresponding profile intensity plot of the selected (square) region. Scale bar: 10µm, J quantification pooled control (C0=10, C1=10 and C2=10) n=30 and pooled mutant TDP-43 (P1=10, P2=10 and P3=10) n=30 cells from each differentiation. Unpaired Mann-Whitney-test.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "Western blots showing nucleo-cytoplasmic fractionation of WT-mCherry and MUT-mCherry iPSC-derived motor neurons with F (left panel) quantification of total mCherry and total untagged TDP-43 on α-tubulin and (right panel) relative cytoplasmic mCherry and untagged TDP-43 on total mCherry and total untagged TDP-43 respectively",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "Representative kymographs from control and mutant TDP-43 iPSC-derived motor neurons. The x-axis represent distance in µm while on the y-axis time in seconds is revealed. Stationary mitochondria are visible as straight vertical lines, while moving mitochondria are depicted as skewed lines. B Quantification of percentage of moving mitochondria.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "Immunofluorescent analysis of TDP-43 in control, mutant TDP-43 and mutant TDP-43+HDAC6 inhibitor after 12 h treatment. Presented immunofluorescent images of control (C2) and mutant TDP-43 (P2). Scale bar: 25µm. B Profile intensity plot of control, mutant TDP-43 and mutant TDP-43+HDAC6 inhibitor. C Quantification of nucleo-cytoplasmic ratio (N/C) fluorescent intensity of TDP-43 in motor neurons, each dot represents one analyzed cell, unpaired Mann-Whitney-test.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "B PCR performed on genomic DNA with indicated primers as shown: o1: oPAP8_rtpF, o2: oPAP8_E3R, o3: oPAP8_rtpR, oLB: oLBb1.3, EF1α: ELONGATION FACTOR 1α, WT: wild type, pap8-1: Homozygous albino plant, Ht: Heterozygous green plant; T: T-DNA, arrowhead: 670-bp contaminant amplification product used as loading control.",
    "ncbi_link": "EF1α: 
ELONGATION FACTOR 1α: 
PAP8: 814720
pap8: 814720"
  },
  {
    "caption": "C RT-PCR on wild type and pap8-1 homozygous plants grown in the dark for 3 days followed with 72-h growth under white light to allow greening of the wild type; EF1α used as control.",
    "ncbi_link": "EF1α: 
pap8: 814720"
  },
  {
    "caption": "F Mutant Rescue: WT and two representative pap8-1 plants were grown in vitro using sucrose and low white light intensity (of 10 µmol.m-2.s-1); scale bar equals 20 mm.",
    "ncbi_link": "pap8: 814720"
  },
  {
    "caption": "B Two or six (-97m3) representative primary transformants expressing GUS under the given PAP8 promoter version; FC+, the corresponding promoters were tested positive in functional complementation of the mutant pap8-1. Scale bar equals 3 mm.",
    "ncbi_link": "PAP8: 814720
pap8: 814720"
  },
  {
    "caption": "D Dual luciferase reporter assay; Renilla luciferase (Rluc) used as internal control and GFPer used as control for the transfected area; the promoters driving Firefly luciferase (Fluc) were transfected in onion epidermis cells without or with constitutively expressed HY5. The Fluc/Rluc activity was set to 1 for the minus-HY5 control; mean ± standard error corresponding to 3 replicates; photon counts are given in source data. *, ε-test = 3,43 > 1.96 corresponding to p-value < 0,001.",
    "ncbi_link": "Renilla luciferase: 
Firefly luciferase: 
Fluc: 
GFP: 
Rluc: "
  },
  {
    "caption": "E Electro-mobility shift assay of a probe corresponding to the near palindromic PAP8 element (GAcGCTC) with recombinant HY5 protein; a probe containing a canonical G-box element (CACGTG) recognized by HY5 was used as cold competitor.",
    "ncbi_link": "PAP8: 814720"
  },
  {
    "caption": "F Integrative genomics viewer (IGV) images of the Chromatin immunoprecipitation (ChIP) sequencing data30 at the PAP8 locus; TAIR10, annotation according to the Arabidopsis thaliana information resource orange box indicates the PAP8 locus. ChIP on hy5-ks50; 35S:HY5-YFP exposed to blue light or red light using GFP antibody and compared to mock corresponding to ChIP control experiment done without antibody. Each treatment is presented as track overlay of triplicates: the read count is given within the \"group autoscale\" range in brackets. Close up on the 5'-UTR region centred on the -95-promoter element in yellow.",
    "ncbi_link": "PAP8: 814720"
  },
  {
    "caption": "B Transiently expressed PAP8FL-GFP (full-length coding sequence of PAP8 fused to GFP) in onion epidermal cells displays a dual localization in the nucleus (white arrowhead) and in plastids (yellow arrowheads).",
    "ncbi_link": "GFP: 
PAP8: 814720"
  },
  {
    "caption": "D-G Co-expression analysis of PAP8FL-GFP (D) with PAP8ΔcTP-RFP (E) in onion epidermal cells; (F) green and red channels merged; yellow arrowheads show plastids; white arrowheads show nuclei as observed with DIC, differential interference contrast in (G); FL, PAP8 full length ORF; ΔcTP, deletion of the cTP; scale bars equal 20 µm.",
    "ncbi_link": "PAP8: 814720"
  },
  {
    "caption": "C-G Pictures of representative genotypes obtained in the functional complementation test of pap8-1 using pP8::PAP8-NLSm5 (C, F) or pP8::PAP8ΔcTP (G) both constructions without GFP tags; ⌀ indicates pap8-1 without any PAP8 transgene. (D-G) Pictures using Keyence technology of plants with genotypes as labelled; transgenes expressed using the 1.1-kb PAP8 promoter. Scale bars equal 1 mm.",
    "ncbi_link": "GFP: 
pap8: 814720
PAP8: 814720"
  },
  {
    "caption": "A Phenotypes of given genotypes subjected to 5 days of illumination at 8 µmol.m-2.s-1 660-nm red light. PBG, pCaMV35S::PHYB-GFP transformed in pap8-1/+ (among 25 lines selected for GFP expression see data source; 2 doubly heterozygous pap8-1/+; PBG/- lines #6 and #7 segregated the photobodies alteration with the albinism).",
    "ncbi_link": "GFP: 
pap8: 814720
PHYB: 816394"
  },
  {
    "caption": "B Hypocotyl length, given as the mean ± SD, of plants grown as in (A) (R8, grey bars) or at 30 µmol.m-2.s-1 660-nm red light (R30, pink bars) showing partial insensitivity of pap8-1 to the PBG overexpression. Measurements are given in source data; in the order of the graph n equals (50, 133, 58, 43, 36, 112, 25, 60) δ-test (comparison of the mean) R8: δPBG/PBGp8-1= 20.38 corresponding to p-value < 10-31 δwt/p8-1= 0.5 < 1.96 not significant at α set to 0.05).",
    "ncbi_link": "pap8: 814720"
  },
  {
    "caption": "H Immuno-blots using a GFP antibody or a PAP8 antibody showing respectively the levels of PHYB-GFP and PAP8 in the given genotypes grown in the dark for 3 days or in light; n.a., not applicable as the pap8-1 mutant can only be visually distinguished from wild type after light exposure; 2 lines (L#06 and L#07) for PBG/pap8-1 were tested. Coomassie blue staining presented as loading; signals were quantified using ImageJ.",
    "ncbi_link": "pap8: 814720"
  },
  {
    "caption": "I RT-qPCR analysis on wild type, pap8-1, PBG and PBG pap8-1. Seedlings were grown in the dark (D) or under white light (L, 30 µmol.m-2.s-1); levels of transcripts are given relative to EF1α; error bars correspond to standard errors on technical triplicates and the dark sample is the wild-type PBG line. δ-test (comparison of the mean) ***, P < 10-72.",
    "ncbi_link": "EF1α: 
pap8: 814720"
  },
  {
    "caption": "J Immuno-blots showing the levels of PIF1, PIF3, HY5 in given genotypes grown in the Dark or Light condition as noted: p5/+, mix of an heterozygous pap5-2 siblings progeny undistinguishable from wild type; p5-2, pap5-2 and pifq, quadruple pif1-1 pif3-3 pif4-2 pif5-3 mutant; Histone H3 (H3), RbcL and PAP8 were used as controls; n.a., not applicable.",
    "ncbi_link": "pif1: 
pif3: 
pif5: 
pap5: 841727
pif4: 818903"
  },
  {
    "caption": "(D) Representative western blot of HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) and HTT pT3 (ab-CHDI-90001528-1) upon coexpression of HTTex1 16Q and 72Q eGFP with the indicated kinases for 48 hour in HEK293T cells.",
    "ncbi_link": "eGFP: 
HTT: 3064"
  },
  {
    "caption": "(A) Representative western blot of HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) and HTT pT3 (ab-CHDI-90001528-1) upon coexpression of HTTex1 16Q eGFP, mutants with S to A substitutions at T3 or S13/S16 or HTTex1 72Q eGFP with TBK1 or TBK1 kinase-dead (KD) for 48 hour in HEK293T cells (the additional high molecular weight HTTex1 and HTT pS13 band is possibly due to the co-occurrence of phosphorylation at both S13 and T3). (B) Quantification of the fold changes in the HTT pS13 (upper panel) and pT3 (lower panel) ratio to total HTT compared to those of the kinase-dead mutant from the experiments like in A (n=3). ",
    "ncbi_link": "eGFP: 
HTT: 3064
TBK1: 29110"
  },
  {
    "caption": "(C) Representative western blot of HTT (ab-MAB2166) and HTT pS13 (ab-CHDI-90001039-1) upon coexpression of HTT N543 55Q with the indicated kinase for 24 hour in HEK293T cells. (D) Quantification of HTT pS13 using the Singulex assay (using ab-MW1 as capture and CHDI-90001039 or 2B7 as detection antibodies for pS13 or total HTT) upon coexpression of HTT N543 55Q with the indicated kinase for 24 hour in HEK293T cells from the experiment in C (representative of 3 repeats). ",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(E) Representative western blot of HTT (ab-MAB2166) and HTT pS13 (ab-CHDI-90001039-1) upon coexpression of HTT-FL 48Q or HTT-FL 48Q S13A/S16A with the indicated kinase for 24 hour in HEK293T cells. (F) Quantification of HTT pS13 using the Singulex assay (using ab-MW1 as capture and CHDI-90001039 or 2B7 as detection antibodies for pS13 or total HTT) upon coexpression of HTT-FL 48Q or HTT-FL 48Q S13A/S16A with the indicated kinase for 24 hour in HEK293T cells from the experiments likein E (n=3). ",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(G) Representative western blot of immunoprecipitated (IP) HTT (ab-MAB2166) and HTT pS13 (ab-CHDI-90001039-1) after lentivirus (LV)-mediated overexpression of TBK1 or TBK1 KD for 72 hour in rat primary striatal neuronal cells. (H) Quantification of the fold changes in the HTT pS13 ratio to total HTT compared to those of the kinase-dead mutant from the experiments like in G (n=3). ",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(A) Representative western blot of soluble HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) and HTT pT3 (ab-CHDI-90001528-1) upon coexpression of HTTex1 16Q eGFP or 72Q eGFP or its phosphorylation-incompetent mutants with the indicated kinases for 48 hour in HEK293T cells. (B) The graph indicates the fold change in HTT in samples like illustrated in A, relative to empty vector controls normalized to GAPDH. ",
    "ncbi_link": "eGFP: 
HTT: 3064"
  },
  {
    "caption": "(C) Representative immunoblot of the HTT (ab-MAB5492) after filter retardation assay from the insoluble cellular fraction upon expression of HTTex1 16Q eGFP or 72Q eGFP or its phosphorylation-incompetent mutants with the indicated kinases for 48 hour in HEK293T cells. (D) Quantification of the fold change in HTT aggregates compared to EV expressing HTTex1 16Q from the experiments like in C. ",
    "ncbi_link": "eGFP: 
HTT: 3064"
  },
  {
    "caption": "(E) Representative immunofluorescence images of HTT aggregates (eGFP) and TBK1 (ab-anti-MYC) upon coexpression of HTTex1 72Q eGFP or its phosphorylation-incompetent mutants with the indicated kinases for 48 hour in HEK293T cells (scale bar 20μm).",
    "ncbi_link": "eGFP: 
HTT: 3064"
  },
  {
    "caption": "(H) Representative western blots of HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) in soluble fraction and aggregates from HEK293T cells transfected first with HTTex1 72Q eGFP and then after 48 hour (to enable the formation of aggregates before the kinase expression); with TBK1; cells were lysed at the indicated time after kinase transfection. (I) Quantification of the percentage of cells presenting aggregates and kinase expression from the experiments in H. ",
    "ncbi_link": "eGFP: 
HTT: 3064
TBK1: 29110"
  },
  {
    "caption": "(A Quantification of cell death by a nuclear condensation assay, cells were fixed and the nuclei were stained with Hoechst dye, cells with a nuclear intensity higher than the average intensity plus two standard deviations are considered dead. (A) The percentage of cell death at DIV14, after co-transfection of indicated kinases and HTTex1 plasmid in rat primary striatal neurons at DIV9 (n=3),",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "B) Quantification of cell death by a nuclear condensation assay, cells were fixed and the nuclei were stained with Hoechst dye, cells with a nuclear intensity higher than the average intensity plus two standard deviations are considered dead. (B) The percentage of cell death at DIV7, after co-transfection of indicated kinases and HTT N586 plasmid in mouse primary striatal neurons at DIV5 (n=8).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(C) Quantification of cell death by a TUNEL assay in rat primary striatal neurons transfected with the indicated kinases at DIV9 with the indicated HTT plasmid. The cells were fixed at DIV14, and the percentage of TUNEL-positive neurons was counted and plotted (n=3).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(D) The percentage of cell death., quantification by a nuclear condensation assay in mouse primary cortical neurons co-transfected with the indicated HTT N586 and kinases at DIV5, cells were treated with TBK1 inhibitor MRT 68601 at DIV5 till DIV7. Cells were fixed, and the nuclei were stained with Hoechst dye (n=3).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(E) Quantification of cell death by a TUNEL assay in mouse primary striatal neurons transfected with the indicated kinases at DIV9 with the indicated HTT plasmid. The cells were fixed on DIV14, and the percentage of TUNEL-positive neurons was counted and plotted (n=3).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(A) Representative immunofluorescence image of C. elegans overexpressing HTT N513 Q15 and HTT N513 Q128 (scale bar 20μm). Top panel complete worm, lower panel head region.",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(B) Western blot showing HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) and HTT pT3 (ab-CHDI-90001528-1) levels in C. elegans overexpressing HTT N513 Q15 and HTT N513 Q128. (C) Quantification of the fold changes in ratios of HTT pS13 and pT3 to total HTT in C. elegans overexpressing HTT N513 Q15 and HTT N513 Q128 from the experiments like in B (n=3). ",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(D) Representative western blots showing the HTT (ab-MAB5492) and HTT pS13 (ab-CHDI-90001039-1) levels from the detergent soluble fraction and HTT aggregates (ab-MAB5492) from the detergent insoluble fraction in three different transgenic C. elegans lines overexpressing TBK1 or the TBK1 KD. (E) The bottom graph indicates the fold change in the HTT pS13 (ab-CHDI-90001039-1) ratios to total HTT (ab-MAB5492) compared to those in the kinase-dead mutant line 1 from the experiments like in D. The top graph indicates the fold change in HTT aggregates (ab-MAB5492) compared to that in the kinase-dead mutant the experiments like in D (n=3). ",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(F) Mobility of the Q15 and Q128 C. elegans lines upon overexpression of TBK1 or TBK1 KD (n= 26-29).",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(G) Survival graph of the Q15 and Q128 C. elegans lines upon overexpression of TBK1 or TBK1 KD (n=30).",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(H) Representative western blots showing HTT (ab-MAB5492) and HTT pS13 (ab-CHDI-90001039-1) from the detergent soluble fraction and HTT aggregates (ab-MAB5492) from the detergent insoluble fraction in TBK1 orthologue (ikke-1 or unc-51) RNAi-treated C. elegans lines expressing HTT N513 Q15 and HTT N513 Q128. (I) Quantification of the fold change in the ratio of pS13 HTT to total HTT compared to non-targeting RNAi from the experiments like in H (n=4). ",
    "ncbi_link": "HTT: 3064
ikke-1: 176278
unc-51: 180311"
  },
  {
    "caption": "(A) Representative immunoblot of a filter retardation of HTT (ab-MAB5492) from the insoluble cellular fraction; HEK293T cells co-expressed HTTex1 72Q eGFP and TBK1 or TBK1 KD for 48 hour, and for the last 16 hour, they were treated with the indicated proteasome inhibitor (MG132, 5 µM) or autophagy inhibitor (Baf A1, 200 nM, NH4Cl, 10 mM, 3-MA,5 mM). (B) Quantification of the fold change in HTT aggregates compared to TBK1 KD treated with DMSO from the blots like in A (n=3).",
    "ncbi_link": "eGFP: 
HTT: 3064
TBK1: 29110"
  },
  {
    "caption": "(C) Immunoblot of LC3 (ab48394) from soluble HEK293 cellular fractions overexpressing TBK1 or TBK1 KD for 24 hour; for the last hour, Baf A1 (500 nM) was added as indicated. (D) Fold change in LC3-II levels (lower band) relative to the respective untreated kinase dead mutant normalized to actin from the blots like in C (n=3). ",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(E) Immunoblot of LC3 (ab48394) from soluble rat primary neuronal cells overexpressing lentivirus-mediated TBK1 and TBK1 KD for 96 hour. For the last 1 or 4 hour, Baf A1 (500 nM) was added as indicated. (F) Quantification of the fold change in LC3-II levels (lower band) compared to the kinase dead mutant, which was untreated, normalized to GAPDH from the blots like in E (n=3).",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(A) Western blot of soluble HTT (ab-MAB5492), HTT pS13 (ab-CHDI-90001039-1) and HTT aggregates (ab-MAB5492), upon coexpression of the HTTex1 72Q eGFP or HTTex1 72Q eGFP S13A/S16A variant with TBK1 KD, TBK1 or TBK1 Δ690-713 for 48 hour in HEK293 cells. (B) The graph indicates the calculated fold changes in HTT, HTT pS13 ratio to total HTT and HTT aggregates all compared to the levels in TBK1 KD from the experiments like in A (bottom panel normalized to Tubulin, n=3). ",
    "ncbi_link": "eGFP: 
HTT: 3064
TBK1: 29110"
  },
  {
    "caption": "(C) Representative immunofluorescence images of eGFP HTTex1 72Q or its phosphorylation-deficient variant S13A/S16A upon coexpression with TBK1 KD or TBK1 or TBK1 Δ690-713 (ab-anti-Myc) with for 48 hour in HEK293 cells (scale bar 20μm). (D) The graph indicates the percentage of co-transfected cells presenting aggregates upon expression of the indicated kinase, from the experiments like in C (n=3). ",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(E-G) Primary cortical neurons from E15 cerebral cortices were transfected with the indicated plasmids, incubated for two days in vitro and treated with Tf-555 for 30 minutes before fixation. Cells were immunostained with the indicated antibodies. The images are obtained with high-resolution microscopy (Nikon). Blue alone channels are shown in black and white images. Lower panels in (E) and (F) are high magnification images indicated by white or blue rectangles in upper panels. The graph in (G) shows the Pearson's correlation coefficient of Tf-555 and Rab11 or APPL1. Each score represents the mean with the individual points. Control: n = 23 cells, Rab21-sh115: n = 18 cells, Rab5-sh232 (Tf - Rab11): n = 23 cells, Rab5-sh232 (Tf - APPL1): n = 22 cells.",
    "ncbi_link": "Rab21: 216344
Rab5: 54189"
  },
  {
    "caption": "Cerebral cortices at E17, electroporated with the indicated plasmids plus pCAG-EGFP at E14. (C) The ratio of locomoting neurons with more than three primary neurites in the IZ. Each score represents the mean with the individual points. Control: n = 4 brains (60 cells), Rab21-sh115: n = 3 brains (65 cells), Rab5-sh232: n = 4 brains (111 cells).",
    "ncbi_link": "EGFP: 
Rab21: 216344
Rab5: 54189"
  },
  {
    "caption": "(E) Time-lapse imaging of control and Rab21-sh115-electroporated cells in cortical slices from E16 cerebral cortices, electroporated with the indicated plasmids at E14. After formation of the leading process, control neurons rapidly eliminated their immature neurites (yellow arrows), whereas the Rab21-knockdown neurons retained the immature neurites (white arrows) for long periods. Time interval of each frame is 30 min.",
    "ncbi_link": "Rab21: 216344"
  },
  {
    "caption": "Primary cortical neurons from E15 cerebral cortices were transfected with pCAG-PM-mAG1 (green) and incubated for two days in vitro. Cells were immunostained with the indicated antibodies (red and blue/white). The transfected PM-mAG1 is a marker for the plasma membrane. The images are obtained with high-resolution microscopy (Nikon) and the lower panels are high magnification images near the plasma membrane. Blue alone channels are shown in black and white images. Each score represents the mean of ratios with the individual points. Rab5: n = 18 cells (middle and right), Rab21: n = 31 cells (left and middle) or 20 cells (right), Caveolin-1: n = 43 cells (left).",
    "ncbi_link": "mAG1: "
  },
  {
    "caption": "Primary cortical neurons from E15 cerebral cortices were transfected with the indicated plasmids plus pCAG-EGFP , incubated for two days in vitro and treated with BODIPY-LacCer (LacCer) (green) (A-B) for 30 minutes before fixation. White arrows in (A) indicate the perinuclear accumulation of LacCer. Blue alone channels are shown in black and white images. The graphs in (B) show the ratio of cells with perinuclear accumulation of LacCer (B) which was quantified in a blinded counting. Each score represents the mean with the individual points. B: n = 5 biological replicates (Control: 115 cells, Cav1-sh490: 127 cells, Rab21-sh115: 136 cells, Rab5-sh232: 216 cells, Rab21-sh115 + wt-Rab21: 132 cells)",
    "ncbi_link": "EGFP: 
Cav1: 12389
Rab21: 216344
Rab5: 54189"
  },
  {
    "caption": "Primary cortical neurons from E15 cerebral cortices were transfected with pCAG-PM-mAG1, incubated for two days in vitro and stained with the indicated antibodies. Blue alone channels are shown in black and white images. Arrowheads indicate accumulation of N-cadherin at the plasma membrane. Lower panels in (D) are high magnification images indicated by white or blue rectangles. The images are obtained with high-resolution microscopy (Nikon).",
    "ncbi_link": "mAG1: "
  },
  {
    "caption": "Immature neurons in the IZ of the cerebral cortices at E17, electroporated with the indicated plasmids plus pCAG-PM-mAG1 and pCAG-HA-N-cadherin at E14. Frozen sections were immunostained with anti-mAG1 and anti-HA antibodies. Arrow and arrowheads indicate the accumulation of HA-N-cadherin at the perinuclear regions or the plasma membrane, respectively. Control: n = 77 cells from 3 biological replicates, Rab21-sh115: n = 108 cells from 3 biological replicates.",
    "ncbi_link": "HA: 
mAG1: 
N-cadherin: 12558
Rab21: 216344"
  },
  {
    "caption": "(A-B) Primary cortical neurons from E15 cerebral cortices were transfected with the indicated plasmids plus pCAG-PM-mAG1 (green) and incubated for two days in vitro. Immunocytochemical analyses with anti-caveolin-1 (red) antibody were performed. The images are obtained with high-resolution microscopy (Nikon). The graph in (B) indicates the ratio of the caveolin-1 staining signals in the plasma membrane to total fluorescence intensities of caveolin-1 in each immature neuron. Each score represents the mean of ratios with the individual points. Control: n = 20 cells, Rab21-sh115: n = 22 cells, Rab21-sh115 + wt-Rab21: n = 23 cells. Overexpression of wt-Rab21 resulted in neuronal cell death, which making it difficult to determine the accurate DNA concentration of wt-Rab21 in the rescue experiments.",
    "ncbi_link": "mAG1: 
Rab21: 216344"
  },
  {
    "caption": "(H-I) Primary cortical neurons from E15 cerebral cortices were transfected with the indicated plasmids, incubated for two days in vitro, treated with Bafilomycin A1 (Baf A1) for 6 h and stained with the indicated antibodies. The images are obtained with high-resolution microscopy (Nikon) and the lower panels are high magnification images of the lysosomes, indicated by white or blue rectangles. Blue alone channels are shown in black and white images. The graph in (I) shows the Pearson's correlation coefficient between caveolin-1 and Lamp1, a lysosomal marker, in control and Rab21-sh115-transfected neurons. Each score represents the mean of ratios with the individual points. Control: n = 31 cells, Rab21-sh115: n = 22 cells.",
    "ncbi_link": "Rab21: 216344"
  },
  {
    "caption": "(A) Locomoting neurons in the upper IZ of the cerebral cortices at E17, electroporated with the indicated plasmids plus pCAG-EGFP at E14. (B) The ratio of locomoting neurons with more than three primary neurites. Each score represents the mean of ratios with the individual points. Control: n = 4 brains, Rab21-sh115: n = 5 brains, Rab21-sh115+Caveolin-1: n = 6 brains. (C) The box-and-whisker plot shows average leading process length of the locomoting neurons in the IZ. Control: n = 115 cells, Rab21-sh115: n = 188 cells, Rab21-sh115+Caveolin-1: n = 185 cells. (",
    "ncbi_link": "EGFP: 
Caveolin-1: 12389
Rab21: 216344"
  },
  {
    "caption": "(D-E) Cerebral cortices at P0, electroporated with the indicated plasmids plus pCAG-EGFP at E14. The lower graphs in (D) and the graph in (E) show the estimation of cell migration, as measured by EGFP fluorescence intensities in distinct regions of the cerebral cortices using Leica SP5 software. Each bar in the graph in (E) represents the mean percentage of relative intensities. Rab21-sh115: n = 4 brains, Rab21-sh115+CAG-wt-caveolin-1: n = 6 brains. II-IV: layers II-IV of the cortical plate, V-VI: layers V-VI of the cortical plate, IZ: intermediate zone, WM: white matter, SVZ/VZ: subventricular zone/ventricular zone.",
    "ncbi_link": "EGFP: 
caveolin-1: 12389
Rab21: 216344"
  },
  {
    "caption": "Western blot for p53, phosphorylated p53 at Ser15 (p53 pS15), and vinculin (vinc) in HCT116 treated with 300 μM 5-FU for 8 h and silenced for PHD1, PHD2, or PHD3.",
    "ncbi_link": "PHD2: 54583
PHD1: 112398
PHD3: 112399"
  },
  {
    "caption": "qRT-PCR for PHD1, PHD2, and PHD3 in HCT116 silenced for PHD1 (*P = 0.0006 toward Scr), PHD2 (*P = 0.0004 toward Scr), or PHD3 (*P = 0.0075 toward Scr). A two-tailed unpaired t-test was performed with n = 3/group.",
    "ncbi_link": "PHD2: 54583
PHD1: 112398
PHD3: 112399"
  },
  {
    "caption": "Western blot of p53 pS15, p53, PHD1, and vinculin in HCT116 treated with 300 μM 5-FU for 8 h and silenced for PHD1 or a scrambled (Scr) control.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "qRT-PCR for PHD1 showing silencing efficacy with both siRNAs 1 (*P = 0.0017 toward Scr) and 2 (*P = 0.0023 toward Scr) compared to the scrambled control in HCT116. A two-tailed unpaired t-test was performed with n = 3/group.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for p53, p53 pS15, and vinc in HCT116 silenced for PHD1 with two different constructs (constructs 1 and 2) upon exposure to 300 μM 5-FU for 8 h.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for p53 pS15, p53, and vinculin in HCT116 silenced for PHD1 and treated with either 200 nM SN-38 or 20 μM oxaliplatin for 8 h.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "RNA levels of PHD1 in LIM1215 silenced for PHD1. (*P = 0.0099 toward Scr in a two-tailed unpaired t-test with n = 3/group.)",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for p53 pS15, p53, and vinc in LIM1215 upon silencing of PHD1 and treatment for 8 h with 200 μM 5-FU.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "A Western blot for p53, cleaved caspase-3 (cleaved casp3), cleaved parp, and vinculin (vinc) in p53wt/wt and p53−/− HCT116 silenced for PHD1 upon exposure to 300 μM 5-FU for 24 h, showing an increased apoptotic response to 5-FU treatment in PHD1-silenced cells compared to the scrambled control.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "B Confirmation of these results by FACS analysis of propidium iodide-stained PHD1-silenced p53wt/wt and p53−/− HCT116 cells exposed for 26 h to 300-μM 5-FU treatment. *P = 0.002 toward p53wt/wt HCT116 shScr 5-FU-treated (two-tailed unpaired t-test) with n = 6 for non-treated p53wt/wt HCT116 and n = 3 in all other groups.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "C Detection of cleaved casp3, cleaved parp, and vinc in HCT116 silenced with a second siRNA for PHD1.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "D, E Apoptosis as detected by Western blot for cleaved casp3 and parp in PHD1-silenced HCT116 treated for 20 h with 200 nM SN-38 (D) or for 24 h with 20 μM oxaliplatin (E).",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "F Western blot for cleaved casp3, parp, and vinc in LIM1215 silenced for PHD1 and treated for 24 h with 200 μM 5-FU.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "G Similar apoptosis levels were detected by Western blot for cleaved casp3 and parp with vinc as a loading control in p53S15A→p53−/− HCT116 silenced for PHD1 or scrambled (Scr) control and treated for 20 h with 300 μM 5-FU.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Representative images and quantification of the colony formation capacity of p53wt/wt HCT116 cells transduced with a doxycycline-inducible shScr or shPHD1 silencing construct, treated for 24 h with doxycycline with or without additional treatment for 8 h with 300 μM 5-FU. *P = 0.008 toward shScr, two-tailed unpaired t-test and n = 3/group.",
    "ncbi_link": "PHD1: 112398
p53: 22059"
  },
  {
    "caption": "Tumor volume of p53wt/wtHCT116 cells transduced with a doxycycline-inducible shScr or shPHD1 silencing construct injected subcutaneously in nude mice and treated with 5-FU. *P = 0.045 toward shScr 5-FU-treated mice by two-way ANOVA with n = 6 for p53wt/wtHCT116 shScr, n = 7 for p53wt/wtHCT116 shPHD1 and p53wt/wtHCT116 shScr 5-FU-treated, and n = 8 for p53wt/wtHCT116 shPHD15-FU-treated.Tumor volume of p53−/−HCT116 cells transduced with a doxycycline-inducible shScr or shPHD1 silencing construct injected subcutaneously in nude mice and treated with 5-FU. n = 6 for p53−/−HCT116 shScr, p53−/−HCT116 shPHD1, and p53−/−HCT116 shScr 5-FU-treated and n = 8 for p53−/−HCT116 shPHD15-FU-treated.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Western blot for p53 pS15, p53, and vinculin (vinc) in PHD1-silenced HCT116 upon treatment with 300 μM 5-FU for 8 h with or without 0.5 mM DMOG for 26 h. Vinculin (vinc) is used as a loading control.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot detection of PHD1-Flag and p53 in whole cell extracts (WCE) or after immunoprecipitation against the Flag-tag of overexpressed PHD1-Flag in HEK293T cells.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot detection of PHD1-Flag and p53 after immunoprecipitation against the Flag-tag of recombinant PHD1-Flag incubated with recombinant p53.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for p53 and PHD1 in WCE or after immunoprecipitation of endogenous p53 in p53wt/wt HCT116 cells, silenced with a Scr control, siPHD1, or sip53, or after immunoprecipitation of p53wt/wt HCT116 cell lysates with an IgG control.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Western blot for p53 pS15, p53, and vinculin (vinc) in HCT116 treated with 300 μM 5-FU upon silencing of PHD1 and p38α, alone or in combination. Vinculin (vinc) is used as a loading control.",
    "ncbi_link": "PHD1: 112398
p38α: 1432"
  },
  {
    "caption": "Detection of p53 pS15 and p53 after in vitro phosphorylation by p38α, p38β, or p38γ of p53immunoprecipitated from cells silenced for a control (SIMA) or PHD1.",
    "ncbi_link": "PHD1: 112398
p38β: 5600
p38γ: 6300
p38α: 1432"
  },
  {
    "caption": "Detection by Western blot of p53 and p38 from whole cell extracts (WCE) or after immunoprecipitation of p53 from cell silenced for a Scr control or siPHD1 and treated for 1 h with 300 μM 5-FU.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Transcription analysis of CDKN1A, GADD45, MDM2, BAX, PUMA in PHD1-silenced p53wt/wt HCT116 either untreated or treated for 8 h with 300 μM 5-FU.",
    "ncbi_link": "BAX: 581
PUMA: 27113
CDKN1A: 1026
PHD1: 112398
GADD45: 1647
MDM2: 4193
p53: 7157"
  },
  {
    "caption": "Western blot for cleaved parp and vinculin (vinc) in PHD1-silenced HCT116 treated for 20 h with 300 μM 5-FU alone or in combination with 3 μg/ml α-amanitin.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "PHD1 mRNA levels in p53R248/− HCT116 silenced for PHD1. *P = 0.0005 toward scrambled control with a two-tailed unpaired t-test and n = 3/group.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Western blot for p53 pS15, p53, and vinculin in PHD1-silenced p53R248/− HCT116 upon 8-h treatment with 300 μM 5-FU.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Western blot for cleaved casp3 and vinculin in p53R248/− HCT116 silenced for PHD1 and treated with 300 μM 5-FU for 24 h.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Western blot for pH2AX and vinculin (vinc) in p53wt/wt and p53−/− HCT116 cells after 24-h treatment with 300 μM 5-FU.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Detection of pH2AX and vinc in p53S15A→p53−/− HCT116 cells silenced for PHD1 and treated with 300 μM 5-FU for 24 h.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Detection of pH2AX and vinc in HCT116 silenced with a second silencing construct of PHD1 and treated for 24 h with 300 μM 5-FU.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for pH2AX and vinc in p53R248/− HCT116 cells silenced for PHD1 upon treatment with 300 μM 5-FU for 24 h.",
    "ncbi_link": "PHD1: 112398
p53: 7157"
  },
  {
    "caption": "Detection by Western blot of p53 and XPB from whole cell extracts (WCE) or after immunoprecipitation of p53 from cells silenced for Scr control or siPHD1 and treated for 4 or 8 h with 300 μM 5-FU.",
    "ncbi_link": "PHD1: 112398"
  },
  {
    "caption": "Western blot for pH2AX and vinc in HCT116 silenced for PHD1 alone or in combination with silencing for XPB upon treatment with 300 μM 5-FU for 20 h.",
    "ncbi_link": "PHD1: 112398
XPB: 2071"
  },
  {
    "caption": "B Western blots and ligand-overlay (O/L) of wheat-germ agglutinin-enriched muscle and fibroblasts lysates from PII.2, PII.5, the healthy sibling (HII.3) and healthy controls (Ctr, Ctr1, and Ctr2) (Muscle: 250μg protein/lane, Fibroblasts: 800μg/lane). In muscle, expression of αDG-IIH6 is reduced but the αDG-Core shows similar expression as controls, with a slight reduction in molecular weight; laminin overlay assay detected some binding activity but was diminished compared to controls, whereas agrin-binding activity showed no difference with controls. In fibroblasts, both αDG-IIH6 and αDG-Core expression and laminin-binding activity were normal, suggesting that unlike other muscular dystrophies, α-dystroglycan glycosylation defect is muscle-specific in POGLUT1 patients.",
    "ncbi_link": "POGLUT1: 56983"
  },
  {
    "caption": "A Protein O-glucosyltransferase activity of wild-type (WT) or D233E mutant POGLUT1 protein toward human factor IX EGF repeat (hFIX-EGF). Wild-type shows higher O-glucosyltransferase activity than D233E, and this activity is dependent on the concentration of the acceptor substrate hFIX-EGF repeat (left) and on the concentration of donor substrate UDP-glucose (UDP-Glc) (right). Values indicate mean ± SEM from three independent assays.",
    "ncbi_link": "POGLUT1: 56983"
  },
  {
    "caption": "B O-glucosyltransferase activity towards five different single EGF repeats from mouse Notch1. Wild-type POGLUT1 shows higher activity toward all EGF repeats tested than POGLUT1D233E. The Y-axis shows the normalized activity relative to wild-type POGLUT1. EGF repeats were at 10 μM. Values indicate mean ± SEM from three independent assays.",
    "ncbi_link": "POGLUT1: 56983"
  },
  {
    "caption": "C Elution profiles of the POGLUT1 reaction products on reverse phase HPLC. hFIX-EGF repeat was incubated with wild-type or D233E mutant POGLUT1 and donor substrate, UDP-Glc or UDP-xylose (UDP-Xyl), at 37ºC overnight. Values on top of the peaks indicate the measured masses. Addition of Glc (162 Da) or xylose (132 Da) to hFIX-EGF (5696.2 Da) by wild-type POGLUT1 caused a shift to an earlier retention time (left). Similarly, the products exhibited a similar shift after incubation with POGLUT1D233E (right). These results indicate that POGLUT1D233E can add a single glucose or xylose to hFIX-EGF repeats and thus has residual enzymatic activity.",
    "ncbi_link": "POGLUT1: 56983"
  },
  {
    "caption": "B-C qRT-PCR on RNA extracted from skeletal-muscle shows that expression of HES1 (B) and PAX7 (C) was significantly lower in D233E patients compared to healthy controls. Mean ± SEM, Student´s t-test (B) and Mann-Whitney U test (C).",
    "ncbi_link": "HES1: 3280
PAX7: 5081"
  },
  {
    "caption": "A-A\" Staining of Drosophila indirect flight muscles at 25% pupal development with 22C10 antibody (myotube marker) and anti-Twist antibody (myoblast marker) indicates that in wild-type animals, indirect flight muscles are formed from 6 myotubes, and a large number of Twist+myoblasts are present.B-B\" rumi79/79 mutants raised at 18C show no obvious defects in myoblast number or myotube morphology.C-D\" rumi79/79 mutants exhibit decreased number of myoblasts at 25°-30°C and either an incomplete set of short myotubes when raised at 25C or aberrant morphology of myotubes when raised at 30C.E-E\" rumi79/79 animals overexpressing FLAG-tagged POGLUT1WT in the muscle compartment using Mef2-GAL4 and raised at 25C during the pupal stage show a rescue of the rumi79/79 muscle phenotype.F-G\" Overexpression of FLAG-tagged POGLUT1D233E only partially rescues the rumi79/79 muscle phenotype, with some variation in the myotube length and the number of restored Twist+cells (compare G and F). Note that the number of Twist+cells restored by POGLUT1D233E is much smaller than that restored by POGLUT1WT. Scale bar in A' is 50 µm and applies to A-G\".H Quantification of myotube lengths in rumi79/79 mutants with or without POGLUT1 expression indicates a weak rescue of the phenotypes by POGLUT1D233E compared to POGLUT1WT. Mean ± standard deviation is shown. The differences in myotube lengths are statistically significant (n = 22-54). Mean ± standard deviation is shown; One-way Anova with Bonferroni´s multiple comparisons test.",
    "ncbi_link": "GAL4: 855828
Mef2: 36032
POGLUT1: 56983
rumi: 326122"
  },
  {
    "caption": "C-D C2C12 myogenic cells showed a reduced level of glycosylated α-dystroglycan when the Notch signaling inhibitor DAPT or LY3039478 was added to the differentiation medium. This indicates that reducing Notch signaling can affect α-dystroglycan glycosylation in wild-type C2C12 myoblasts cells, which do not harbor any known mutations in α-dystroglycan glycosyltransferases or Poglut1.",
    "ncbi_link": "Poglut1: 56983"
  },
  {
    "caption": "E-F qRT-PCR experiments show that upon DAPT or LY3039478 treatment, a remarkable decrease in Hes1 mRNA is induced in C2C12 cells during differentiation.",
    "ncbi_link": "Hes1: 15205"
  },
  {
    "caption": "A panel of selected breast cancer and near normal cell lines was reverse-transfected with 5 nM pooled CEP55 siRNAs and cell viability determined after 6 days. Cell viability relative to its own respective control transfected with scramble siRNA was calculated. Graph represents the mean± SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Immunoblot analysis of CEP55 expression in CEP55 knockdown MDA-MB-231 cells. Two isogenic lines (sh#2 and sh#8) were obtained using two different shRNA sequences as described in method section. COX-IV served as loading control.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Effect of CEP55 knockdown on cell proliferation in MDA-MB-231 cells assessed using the IncuCyte ZOOM® live cell imager (phase-only processing module). The percentage of cell confluence was determined using an IncuCyte mask analyzer. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Representative images of colony forming capacity at 14 days determined using crystal violet staining in control and CEP55 knockdown MDA-MB-231 cells.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Six-week-old female NOD/SCID cohorts of mice were injected in the 4th inguinal mammary fat-pad with the control and CEP55 knockdown cells. Growth rate (area, mm2) of the tumors was measured using digital calliper. Differences in growth were determined using Student's t test. Graph represents the mean tumor area±SEM, n=6 mice/group.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Immunoblots analysis of CEP55 protein expression in MCF10A cells stably transfected with a Flag-CEP55 expression construct and two isogenic lines were obtained (CEP55-#16 and CEP55-#17) with its respective empty vector (EV) transfected parental cells. COX-IV served as a loading control.",
    "ncbi_link": "Flag: 
CEP55: 55165"
  },
  {
    "caption": "Effect of CEP55 overexpression on cell proliferation in MCF10A assessed using the IncuCyte ZOOM® live cell imager as described in panel E. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Representative images of colony forming capacity at 14 days determined using crystal violet staining in empty vector (EV) and CEP55-overexpressing (CEP55#17 and CEP55#18) lines.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Representative images of single plane phase-contrast and Z-stacked immunofluorescence of empty vector (EV) and CEP55-overexpressing MCF10A cells grown on Matrigel for 14 days. Red: Cytokeratin-19; Green: F-actin stained by Phallodin and Blue: DAPI. Z-stack images were acquired through Zeiss LSM 780 confocal microscope-ZMBH.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(A) Polyploidy analysis (>4N DNA contents) determined using FACS in control and CEP55 knockdown MDA-MB-231 cells (left panel). Representative corresponding cytogram showing different phases of cell cycle and the polyploidy subpopulation analyzed using ModFit LT 4.0 software (right panel). Yellow peaks represent subpopulation of polyploidy/aneuploidy. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(B) Analysis of chromosome number in control and CEP55 knockdown MDA-MB-231 cells (sh#8) by Giemsa staining of metaphase spreads (left panel). Representative images showing chromosome spreads assessed by Zeiss AxioScope2 microscopy (right panel). n= number of metaphase spreads counted (mean ±95% confidence interval of two independent experiments).",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(C) Representative SNP array plots showing chromosomal alterations following CEP55-knockdown in MDA-MB-231 cells. BAF is B allele frequency, value between 0 and 1 and represents the proportion contributed by one SNP allele (B) to the total copy number: BAF is an estimate of NB/(NA+ NB), where NA and NB are the number of A and B alleles, respectively.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(D) Percentage of genome altered evaluated using amplified copies (6-8 copies across genome) in both parental and CEP55 knockdown cells determined using data from SNP arrays. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(E) SNP array plots showing chromosomal alterations following CEP55 overexpression in MCF10A cells. Red box indicates an extra chromosome 20 in CEP55-overexpressing cells.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(G) Kaplan-Meier survival analysis of METABRIC data showing the relationship between CEP55 expression and survival. Cases were subdivided into tertiles. Log-rank (Mantel-Cox) test, P< 0.0001.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(A) Representative cytogram of control and CEP55 knockdown MDA-MB-231 cells showing cell cycle profiles following treatment with and without the B12536 (5 nM).",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Percentage of polyploidy (>4N) following B12536 (5 nM) in control and CEP55 knockdown MDA-MB-231 cells. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "Percentage of polyploidy (>4N) following nocodazole (0.5 µM) in control and CEP55 knockdown MDA-MB-231 cells. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(F) Percentage of sub-G1 fraction following B12536 (10 nM) or nocodazole (0.5 µM) in control and CEP55 knockdown Hs578T cells. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(G) Representative cytogram of empty vector (EV) and CEP55-overexpressing MCF10A cells showing cell cycle profile following treatment with and without the B12536 (10 nM).",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(H) Percentage of polyploidy following treatment with and without B12536 (10 nM) in empty vector (EV) and CEP55-overepressing MCF10A cells. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(A) Box and whiskers plot showing average time spent in mitosis and (B) mitotic outcomes in control and CEP55 knockdown MDA-MB-231 cells following treatment with the BI2536 (5 nM). Time taken to complete mitosis was defined as the time from nuclear envelope breakdown until two daughter cells were observed whereas mitotic slippage or death was defined as cells that prematurely exited mitosis with a flattened and a multinucleated phenotype or died during mitosis, characterized by membrane blebbing. Graph represents the mean±SEM of two independent experiments. For each experiments n=50 mitotic cells were counted per condition using Olympus Xcellence IX81 time-lapse microscopy.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(G) Representative mCerulean lifetimes maps of Hs578T control and CEP55 knockdown cells upon nocodazole (0.5 µM) treatment at indicated time points. Cells were synchronized using double thymidine for 16 hours prior to nocodazole treatment.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(H) Quantification of mCerulean lifetimes of control and Hs578T CEP55 knockdow ncells and in response to treatment with nocodazole at indicated time points as shown in G. Blue: 1 ns; red: 3 ns. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(I) Control and CEP55 knockdown MDA-MB-231 cells were synchronized as above, released into culture medium for six hours and then blocked with nocodazole (0.5 µM) for an additional four hours prior to treatment with the Cdk1 inhibitor RO-3306 for an additional 16 hours. Sub-G1 cells were then identified by propidium iodide staining and quantified by FACS. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(J) Control and CEP55 knockdown MDA-MB-231 cells were transfected with MAD2 siRNA (5 nM) for 48 hours followed by nocodazole (0.5 µM) treatment for an additional 12 hours. Cells were collected, fixed and sub-G1 analysis was performed as described in methods. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165
MAD2: 10459///4085"
  },
  {
    "caption": "(C) Relative CEP55 promoter luciferase activity in MDA-MB-231 cells either treated with AZD6244 (1 µM) for 6 hours or ERK1/2 knockdown for 24 hours. PGL basic reporter plasmid was used to normalize basal CEP55 promoter activity. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165
ERK1: 5595"
  },
  {
    "caption": "(E) Relative CEP55 promoter luciferase activity upon MYC siRNA was determined using DualGlo assay in MDA-MB-231 cells similar to experiment in panel C. Graph represents the mean±SEM of two independent experiments.",
    "ncbi_link": "CEP55: 55165
MYC: 4609"
  },
  {
    "caption": "(F) Immunoblots analysis showing MYC and CEP55 expression in MDA-MB-231 cells upon transfection with siRNA against MYC, and ETS1 (10 nM), with and without EGF (100 ng/mL) stimulation as indicated time points. COX-IV served as a loading control.",
    "ncbi_link": "ETS1: 2113
MYC: 4609"
  },
  {
    "caption": "(G) Immunoblots analysis showing CEP55 and MYC levels following 4-hydroxytamoxifen (4OHT) (0.5 µM) induction in MCF10A MYCER cells cultured in 0.1% fetal bovine serum contained media at indicated time points. COX-IV served as a loading control.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(I) Analysis of Pearson correlation coefficients (PCC) of CEP55 vs. MYC transcriptional activity in breast cancer TCGA tumor data with R=0.4157, p<0.0001.",
    "ncbi_link": "CEP55: 55165
MYC: 4609"
  },
  {
    "caption": "(J) Both control and CEP55 knockdown MDA-MB-231 cells were exposed with different concentrations of PLK1 (BI2536) alone (i) or in combination with AZD6244 (1 µM) (ii-iv), and cell viability was determined after 6 days. The dose-response curve was generated by calculating cell viability relative to untreated control and plotted against drug concentration. Graph represents the mean±SEM of three independent experiments.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(L) Immunoblots analysis of both control and CEP55 knockdown MDA-MB-231 cells treated with single and combination treatments after 96h and cleaved PARP, Caspase-3 along with MYC, ERK1/2 and CEP55 were determined. COX-IV as a loading control.",
    "ncbi_link": "CEP55: 55165"
  },
  {
    "caption": "(A) Left, Six week-old female BALB/c cohorts of mice were injected in the 4th inguinal mammary fat pad with the Cep55-ovexpressing mammary carcinoma cell line 4T1.2. Tumor size (area, mm2) was measured using a digital calliper and mean tumor size of each cohort is presented. Mice were treated with vehicle, AZD6244 (12.5mg/kg BID), BI6727 (12.5mg/kg thrice weekly), or combined AZD6244 and BI2536 treatment. Right, representative excised tumor images are shown. Graph represents the mean tumor area±SEM from six mice/group.",
    "ncbi_link": "Cep55: 74107"
  },
  {
    "caption": "E: Colocalization  assays in Kms27  and RPMI8226 MM  cell lines by combining  In Situ Hybridization (FISH) staining  of NEAT1   (Stellaris) with immunofluorescence  of Che-1. Scale bar 10 μm.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "F: (Left) RT-qPCR analysis of NEAT1  expression levels in Kms27 MM  cells transiently transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in technical duplicate (Two Tailed T test ****P<0.001). (Right) Nuclear  extracts from KMS27 MM  cells were immunoprecipitated  with the indicated abs and analyzed by WB with the indicated abs.",
    "ncbi_link": "Actin: 60
NEAT1: 283131
NEAT1A: 283131"
  },
  {
    "caption": "A: Quantitative RT-PCR (RT-qPCR) of Kms27 MM  cells transiently transfected with two different LNA GapmeR NEAT1   or GapmeR Control oligonucleotides. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments performed in duplicate (Two Tailed T test ****P<0.001).",
    "ncbi_link": "Actin: 60
NEAT1: 283131"
  },
  {
    "caption": "C: Representative confocal  images of Kms27 MM  cells transiently transfected with LNA GapmeR NEAT1A, GapmeR NEAT1B  or GapmeR Control oligonucleotides and immunostained  with anti-Che-1 antibody. Scale bar 10 μm.",
    "ncbi_link": "NEAT1A: 283131
NEAT1B: 283131"
  },
  {
    "caption": "D: Isolated cell compartments from Kms27 MM  cells transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides, were subjected to WB  with the indicated abs.",
    "ncbi_link": "NEAT1A: 283131"
  },
  {
    "caption": "E: Che-1 ChIP-seq  signal intensity of LNA GapmeR NEAT1A  (2 replicates on right) and GapmeR Control (2 replicates on left) and at  co-localizing Che-1/NEAT1  sites (N=14654 sites). Signal intensity from 1 (weak) to 12 (strongest).",
    "ncbi_link": "NEAT1: 283131
NEAT1A: 283131"
  },
  {
    "caption": "F: FISH  images of Kms27 MM  cells depleted or not for  Che-1  expression (siChe-1A) labeled with Hoechst  (cell nuclei) and Quasar 670 (NEAT1  RNA). Scale bar 10 μm.",
    "ncbi_link": "Che-1: 26574
Che-1A: 26574
NEAT1: 283131"
  },
  {
    "caption": "G: NEAT1 ChIRP-seq signal intensity of Kms27 MM  cells transiently transfected with siChe-1A or siControl at co-localizing Che-1/NEAT1  sites (N=14654 sites). Signal intensity from 1 (weak) to 14 (strongest).",
    "ncbi_link": "Che-1A: 26574
NEAT1: 283131"
  },
  {
    "caption": "D: Chromatin  extracts from Kms27 MM  cells transfected with LNA GapmeR NEAT1A  or GapmeR Control oligonucleotides were immunoprecipitated  with  S9.6 antibody and analyzed by WB  with the indicated antibodies. Input corresponds to 5% of the total extract used for immunoprecipitation.",
    "ncbi_link": "NEAT1A: 283131"
  },
  {
    "caption": "E: (Left) Representative confocal  images of Kms27 MM  cells treated or not with RNase H, transiently transfected with siChe-1A or siControl and immunostained  with  S9.6 antibody and. Scale bar 10 μm. (Right) Box plot showing S9.6  signal nuclear  intensity per cell (Arbitrary Unit-AU). siChe-1A  cells are described in green color, while siControl in grey color. 100 cells were counted in each replicate. Each dot represents a cell. Median scores per sample are written at the top of the median red line. P value: <1.02-18. ANOVA test was performed to evaluate statistical significance. The red center line denotes the median value (50th percentile) while the black box contains the 25th to 75th percentiles of data. The whiskers mark the 5th and 95th percentiles.",
    "ncbi_link": "Che-1A: 26574"
  },
  {
    "caption": "G: Enrichment density of DRIP-seq  signals at NEAT1/Che1 co-localizing sites in Kms27 MM  cells identified in siRNA control (siControl) (grey) and siRNA Che-1 (siChe-1A) (dark green) samples. Enrichment density was calculated on the relative size of each peak (start to end of each fragment) extended 2000 bp upstream and downstream. Right frame represents the signal obtained from 14654 randomly selected sites from the same experiments.",
    "ncbi_link": "Che-1: 26574
Che-1A: 26574
NEAT1: 283131"
  },
  {
    "caption": "D: (Top) Representative confocal   images of Kms27 MM   cells transfected and treated as in C and immunostained   with S9.6  antibody. Scale bar 10 μm. (Bottom) Box plot showing S9.6  signal nuclear   intensity per cell (Arbitrary Unit-AU). siChe-1A cells are described in dark grey, siChe1A plus CX5461   in green color, while siControl in grey color. Median scores per sample are written at the top of the median red line. P value: <1.30-54. ANOVA test was performed to evaluate statistical significance. The red center line denotes the median value (50th percentile) while the black box contains the 25th to 75th percentiles of data. The whiskers mark the 5th and 95th percentiles.",
    "ncbi_link": "Che-1A: 26574
Che1A: 26574"
  },
  {
    "caption": "E: (Top) Dot blot  analysis of decreasing amounts of genomic DNA   extracts from Kms27 MM  cells depleted or not for Che-1 expression (siChe-1A) and treated with CX5461, were probed using abs directed against RNA:DNA hybrids. (Bottom) Quantification of S9.6 levels by  densitometric analysis. Values were normalized to a Methylene blue  loading control. Error bars represent the standard error of three different biological experiments (Two Tailed T test ****P<0.001).",
    "ncbi_link": "Che-1: 26574
Che-1A: 26574"
  },
  {
    "caption": "A: Differential analysis of siControl vs. siChe1A transcriptome in Kms27 MM  cells. Volcano plot shows 135 significantly upregulated (dark green) and 392 downregulated genes (dark grey). x-axis reports the base-2 logarithm of fold change which is approximated to the B value coming from the statistical Wald test. y-axis reports the base-10 logarithm of Q value of significant genes.",
    "ncbi_link": "Che1A: 26574"
  },
  {
    "caption": "D: WB  analysis of total extracts of Kms27 MM  cells depleted or not for Che-1 (siChe-1A) and probed for the indicated abs.",
    "ncbi_link": "Che-1: 26574
Che-1A: 26574"
  },
  {
    "caption": "E: (Left) Luciferase activity of human NF-kB promoter was measured in Kms27 MM  cells transiently transfected with siChe-1A  or siControl oligonucleotides or with empty vector or p65/RelA   protein expressing vector. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005, ****P<0.001). (Right) WB  analysis of total extracts of Kms27 MM  cells transiently transfected as described in E and incubated with the indicated antibodies.",
    "ncbi_link": "Che-1A: 26574
NF-kB: 4791///4790
p65: 5970
RelA: 5970"
  },
  {
    "caption": "RT-qPCR  analysis of the levels of the indicated genes in Kms27 MM  cells transiently transfected with siChe-1A or siControl. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments in duplicate (Two Tailed T test ***P<0.001, ****P<0.001).",
    "ncbi_link": "Che-1A: 26574
Actin: 60"
  },
  {
    "caption": "G: RT-qPCR analysis of the levels of the indicated genes in Kms27 MM cells transiently transfected with siChe-1A or siControl. Values were normalized to Actin  expression. Error bars represent the standard error of three different experiments in duplicate (Two Tailed T test ***P<0.001, ****P<0.001).",
    "ncbi_link": "Che-1A: 26574
Actin: 60"
  },
  {
    "caption": "H: WB  analysis for the indicated antibodies of total extracts from Kms27 MM  cells with siChe-1A or siControl and where indicated with GFP-tagged RNaseH  expression vectors.",
    "ncbi_link": "GFP: 
Che-1A: 26574
RNaseH: 6050"
  },
  {
    "caption": "I: RT-qPCR analysis of IFNB  and IFNG  levels in Kms27 MM  cells transiently transfected as in H. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test **P<0.01, ***P<0.005.)",
    "ncbi_link": "Actin: 60
IFNB: 3456
IFNG: 3458"
  },
  {
    "caption": "C: Different expression   of IFNG  and IFNB  in Kms27  and U266 MM  cells was assessed by RT-qPCR. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005).",
    "ncbi_link": "Actin: 60
IFNB: 3456
IFNG: 3458"
  },
  {
    "caption": "F: RT-qPCR analysis of IFNG  and IFNB  in U266 MM  cells treated or not with THAP. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ***P<0.005, ****P<0.001) I:  RT-qPCR  analysis of IFNG  and IFNB  levels in Kms27 MM  cells treated as in G. Values were normalized to Actin  expression. Error bars represent the standard error of three different biological experiments performed in duplicate (Two Tailed T test ****P<0.001).",
    "ncbi_link": "Actin: 60
IFNB: 3456
IFNG: 3458"
  },
  {
    "caption": "(C) Dose-dependent antiviral activity of nirmatrelvir in HEK293T-hACE2 cells infected with SARS-CoV-2 D614G (purple symbols), B.1.617.2 (green symbols) or B.1.1.529 (blue symbols). Antiviral activity was determined as percent inhibition of the virus-induced cytopathic effect.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "A Tissue distribution of RIPK2 determined by anti-FLAG immunoprecipitation. Organ homogenates from WT (wild-type) and KI (homozygous FLAG-RIPK2) mice were subjected to anti-FLAG immunoprecipitation and immunoblotting.",
    "ncbi_link": "FLAG: 
RIPK2: 192656"
  },
  {
    "caption": "B Inflammatory signaling in wild-type (WT/WT), RIPK2 CRISPR KO (KO/KO) and FLAG-RIPK2 heterozygous (WT/KI) and homozygous (KI/KI) BMDMs. BMDMs were primed with IFNy, stimulated with MDP for indicated times and analysed by immunoblotting.",
    "ncbi_link": "FLAG: 
RIPK2: 192656"
  },
  {
    "caption": "C Cytokine production of RIPK2 CRISPR KO (KO), wild-type (WT) and FLAG-RIPK2 heterozygous (WT/KI) and homozygous (KI/KI) BMDMs in response to MDP. BMDMs were left untreated or treated with IFNy or IFNy and MDP over-night and cytokines were measured by ELISA. N = 5-8 mice. Shown is average ± SEM. ns = P > 0.05; ** = P ≤ 0.01; **** = P ≤ 0.0001; two-way ANOVA.",
    "ncbi_link": "FLAG: 
RIPK2: 192656"
  },
  {
    "caption": "D Serum cytokines in RIPK2 CRISPR KO (KO), wild-type (WT) and FLAG-RIPK2 heterozygous (WT/KI) or homozygous (KI/KI) mice after i.p. MDP administration. Mice were injected i.p. with PBS or MDP, sacrificed after 4h and serum cytokines were measured by ELISA. N = 3-6 mice. Shown is average ± SEM. ns = P > 0.05; ** = P ≤ 0.01; two-way ANOVA.",
    "ncbi_link": "FLAG: 
RIPK2: 192656"
  },
  {
    "caption": "A Two step enrichment to isolate ubiquitinated RIPK2 from BMDMs. Protein lysates from FLAG-RIPK2 BMDMs (A) were sequentially subjected to ubiquitin enrichment (UBA, B) and FLAG pulldown (C) prior to protein elution and subsequent mass spectrometry analysis.",
    "ncbi_link": "FLAG: 
RIPK2: 192656"
  },
  {
    "caption": "A Activation of the NF-κB pathway by RIPK2 Lysine- and phosphosite mutants. RIPK2-deficient THP-1 cells reconstituted with wild-type RIPK2 or RIPK2 mutants were stimulated with L18-MDP, harvested at indicated time points and activation of the NF-κB pathway was analyzed by immunoblotting.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "B IL-8 production of wild-type THP-1 and RIPK2-deficient THP-1 cells reconstituted with wild-type RIPK2 or RIPK2 mutants and stimulated with L18-MDP was assessed by ELISA. N = 4-8 experiments. Shown is average ± SEM. * = P ≤ 0.05; two-way ANOVA.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "C) RIPK2 ubiquitination determined by UBA pulldown in RIPK2-deficient cells reconstituted with wild-type or mutant RIPK2 after stimulation with L18-MDP.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "D) Detection of K63- and M1-linked ubiquitin chains by UBA pulldown or pulldown with ubiquitin chain type-specific antibodies in RIPK2-deficient cells reconstituted with RIPK2 K209R after stimulation with L18-MDP.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "C Activation of the NF-κB pathway by RIPK2 pocket mutants. RIPK2-deficient THP-1 cells were reconstituted with wild-type RIPK2 or RIPK2 mutants, stimulated with L18-MDP, harvested at indicated time points and analyzed by immunoblotting. ­",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "D IL-8 production of RIPK2-deficient THP-1cells reconstituted with wild-type RIPK2 or RIPK2 mutants and stimulated with L18-MDP was assessed by ELISA. N = 3-8 experiments. Shown is average ± SEM. ns = P > 0.05; * = P ≤ 0.05; *** = P ≤ 0.001; **** = P ≤ 0.0001; two-way ANOVA.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "E Ubiquitination of RIPK2 pocket mutants. RIPK2-deficient THP-1 cells were reconstituted with wild-type or mutant RIPK2, left unstimulated or stimulated with L18-MDP and subjected to UBA pulldown and immunoblotting.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "A: Thermal stability assay using selected RIPK2 mutants. THP-1 cells expressing RIPK2 were subjected to heat treatment and the non-denatured fraction was analysed by immunoblotting.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "B: Binding of RIPK2 to XIAP-BIR2. Lysates from RIPK2-deficient THP-1 cells reconstituted with WT or mutant RIPK2 were subjected to pulldown experiments with recombinantly expressed XIAP-BIR2 and analysed by immunoblotting.",
    "ncbi_link": "RIPK2: 8767
XIAP: 331"
  },
  {
    "caption": "(A,B) Representative immunofluorescence microscopy images of the distribution of septin 7 (red), Cdc42 (red) and tubulin (green) in LT-HSCs from borg4fl/fl or borg4∆/∆ mice. Nuclei were stained with DAPI (blue), scale bar= 5 µm. (C) Percentage of cells with a polar distribution of septin 7, Cdc42 or tubulin in borg4fl/fl or borg4∆/∆ LT-HSCs. At least 3 biological repeats, at least 50 cells were scored per sample. Error bars indicate mean±SEM, Two-way ANOVA analysis, ***P<0.001, **P<0.01, *P<0.05. ",
    "ncbi_link": "borg4: 56699"
  },
  {
    "caption": "(D,E) Representative immunofluorescence microscopy images of the distribution of borg4 (red), Cdc42 (red) or tubulin (green) in LT-HSCs from septin 7fl/fl or septin 7∆/∆ mice. Nuclei were stained with DAPI (blue). scale bar= 5 µm. (F) Percentage of cells with a polar distribution of borg4, Cdc42 or tubulin in septin 7fl/fl or septin 7∆/∆ LT-HSCs. At least 3 biological repeats, at least 30 to 50 cells were scored per sample. Error bars indicate mean±SEM, Two-way ANOVA analysis, **P<0.01, *P<0.05. ",
    "ncbi_link": "septin 7: 235072"
  },
  {
    "caption": "(J-O) Percentage of donor derived (borg4fl/fl or borg4∆/∆ or septin 7fl/fl or septin 7∆/∆) B-cells (B220 positive cells), T-cells (CD3 positive cells) and myeloid cells (Mac-1+ or Gr+ positive cells) among BM cells, percentage of donor derived LT-HSCs, ST-HSCs and LMPPs in LSK cells and percentage of donor derived CLPs in lin-Sca1C-kit low cells in animals at post- transplantation (n=12). Error bars indicate mean±SD, ****P<0.0001, **P<0.01 and *P<0.05, Two-way ANOVA analysis and 2 tailed unpaired t-test.",
    "ncbi_link": "borg4: 56699
septin 7: 235072"
  },
  {
    "caption": "(A) Percentage of single LT-HSCs from septin 7fl/fl of septin 7∆/∆ mice that completed first and second division up to 48 hours post initiation of culture. (192 sorted HSCs cells were analysed, error bars indicate mean±SD).",
    "ncbi_link": "septin 7: 235072"
  },
  {
    "caption": "B Analysis of cell differentiation  (left) and proliferation  (right) in the intestine  after CDK8  deletion as in (A). Olfm4, Lysozyme, PAS  and Dclk1 staining  was used to reveal, respectively, stem, Paneth, goblet  and tuft cells. β-Catenin staining  allows detection of cancer cells (cytoplasmic  vs nuclear localisation). Cell proliferation was assessed by PCNA, Ki-67 and BrdU  (2h pulse) staining. Scatter plots represent the percentage of the area stained  by each antibody (relative to the area occupied by hematoxylin). For Paneth  cells, BrdU, PCNA   and Ki67, only crypts  were analysed. For  goblet  cells, crypts  and villi  were analysed. For Tuft cell quantification, Dclk1-positive cells were counted in 50 villi. Colour code depicts small intestine (green), proximal colon  (blue), and distant colon  (red). Mean ± SEM is shown. P-value of unpaired two-tailed t-test is indicated (ns, not significant; p > 0.05). Scale bars, 25μm (Olfm4, Lysozyme, Dclk1  and  β-Catenin) and 50μm (PAS, BrdU,  Ki-67 and PCNA). (n=9 biological replicates)",
    "ncbi_link": "CDK8: 264064"
  },
  {
    "caption": "C Analysis of mouse colon  after AOM/DSS  treatment. Quantification of the number of neoplastic lesions  (n = 10 for Cdk8+/+, and n = 7 for Cdk8 -/- mice). P-value of unpaired t-test is indicated: ns, not significant (p > 0.05). Mean ± SD is shown.",
    "ncbi_link": "Cdk8: 264064"
  },
  {
    "caption": "A Genotyping  confirms the loss of Cdk8  exon 2 in Cdk8 -/- and Cdk8 -/-/Cdk19 -/- organoids after 7 days of OH-tamoxifen  treatment.",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064"
  },
  {
    "caption": "C Left, IHC staining  of WT and Cdk8 -/-/Cdk19 -/- organoids  with Olfm4  (stem cells), Lysozyme  (Paneth cells), Muc2  (goblet cells), and Dclk1  (tuft cells) antibodies. Scale bars, 50μm (Olfm4, Muc2, Dclk1) and 25μm (Lysozyme). Right, quantification of Olfm4, Lysozyme  and Muc2  positive area (% of the total organoid   area as indicated by hematoxylin staining; mean ± SEM), or the number of Dclk1  positive cells per organoid. P-value, unpaired two-tailed t-test: (***) p-value ≤ 0.001; ns, not significant (p > 0.05). 20 different organoids  from 2 biological replicates of each genotype were used for the analysis.",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064"
  },
  {
    "caption": "D WB  of indicated proteins extracted from Wt and Cdk8 -/-/Cdk19 -/- organoids. Included are CFTR  positive and negative control cell line samples obtained from the Cystic Fibrosis  Foundation (CFF). Amidoblack  was used as loading control.",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064
CFTR: 12638"
  },
  {
    "caption": "C Representative  phase contrast  images of organoids  at the indicated  time points  after 7 days of  OH-tamoxifen treatment are shown. Scale bar, 100 μm. D Quantification of the time  needed for mucus  release (observed as a dark staining  in the center of the organoid; mean ± SD are shown). Adjusted p-values of ordinary one-way Anova followed by Tukey's multiple comparison test are indicated: (***) p-value ≤ 0.001; ns: not significant (p > 0.05); (n= 17 for Wt, 11 for Cdk8 -/-, 18 for Cdk19 -/-, and 12 for Cdk8 -/-/ Cdk19 -/- , all biological replicates).",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064"
  },
  {
    "caption": "E Fluorescence confocal microscopy images of Calcein  green-labeled WT and Cdk8-/-/Cdk19-/- organoids  treated with forskolin. Scale bars, 100 μm. F Quantification of forskolin-induced swelling  in WT organoids  treated for 1hour or 24 hours with 0.1μM, 1μM or 10μM Senexin B  (SenB), as indicated, or double KO organoids; DMSO  vehicle was used as control. The surface area of individual organoids  at different time points relative to the area at t = 0 (100%) was measured (mean ± SD, n=8 biological replicates). Linear regression lines are shown.",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064"
  },
  {
    "caption": "H WB  of indicated proteins extracted from Senexin B-treated (10μM, 2h and 24h) organoids  (left), and WT and Cdk8 -/-/ Cdk19 -/- organoids  (right). Amidoblack  was used as loading control.",
    "ncbi_link": "Cdk19: 78334
Cdk8: 264064"
  },
  {
    "caption": "I. SRE-luciferase reporter activity analysis of GICs treated with prazosin in absence or presence of U0126 (10 μM), an inhibitor of the ERK-activating kinase MEK. U0126 prevented prazosin-induced SRE-luciferase activation in GICs.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "G. Decreased PKCδ expression using shRNA counteracts prazosin-induced GIC death. Viability analysis of GICs transduced with scrambled or PKCδ shRNA and treated with prazosin for 72 h. *P < 0.005 by two-tailed unpaired Student's t-test, n=4.",
    "ncbi_link": "PKCδ: 5580"
  },
  {
    "caption": "B. Bioluminescent in vivo images of tumors in mice grafted with GICs expressing either scrambled or PKCδ shRNA. All mice were treated with prazosin (PRZ) for 45 days.C. Quantification of the bioluminescent signals showing that decreased expression of PKC counteracts prazosin inhibition of tumor growth. Fold change in total flux represents the ratio: total flux after treatment/total flux prior treatment. *P=0.0007, n=8, two-sided Mann-Whitney U-test.",
    "ncbi_link": "PKCδ: 5580"
  },
  {
    "caption": "D. Relative quantities of  RNA  in the RNAchIP samples, detected by  RT-qPCR  with primers aligning on the intron1 of the Fosl1 gene as depicted in B (orange arrow). n=3 independent experiments. Data information: Histograms represent mean and s.d. Dots represent individual data points. P-values indicate significantly higher difference between  IP in HP1γ  and in KO cells (***P < 0.001; two-tailed Student's t-test).",
    "ncbi_link": "HP1γ: 12417
Fosl1: 14283"
  },
  {
    "caption": "F. Percentage of RNAchIP   peaks overlapping with indicated chromatin features in  MEF  samples from ENCODE database (green bars). Overlaps was evaluated by comparison with the list of merged peaks whose genomic location was randomized among genes with one hundred permutations (random, gray bars). Data information: Histograms represent mean and s.d. Dots represent individual data points. P-values indicate significantly higher difference between IP in HP1γ and in KO cells (***P < 0.001; two-tailed Student's t-test). ",
    "ncbi_link": "HP1γ: 12417"
  },
  {
    "caption": "E. Left, representative example of a locus on the Ppp3ca  gene surrounding an RNAchIP merged peak, showing the RNAchIP read density as in Fig 1B. Red and orange arrowheads correspond to oriented  CACACA and  GAGAGA  motifs, respectively. Right, sequence of the RNA surrounding a CACACA motif highlighted in red, as well as a second a neighboring imperfect motif. The sequence was used to design a CACACA-containing RNA oligonucleotide probe (CACACA), compared to a control probe (no-CA) devoid of any related motif.",
    "ncbi_link": "Ppp3ca: 19055"
  },
  {
    "caption": "C. Box plot depicting the  length of exon junctions found differentially regulated by MAJIQ between HP1γ (green) and KO (orange) in three categories as in Fig EV5A, all classified differential HP1γ/KO junctions, annotated alternative exon junctions, non-annotated de novo cryptic junctions detected in KO only; n, differential events. Box boundaries represent 25th and 75th percentiles; center line represents median; whiskers indicate ±1.5×IQR; points are values of outliers. Data information: All graphes represent mean and s.d. (** P < 0.005, ***P < 0.001; two-tailed Student's t-test).",
    "ncbi_link": "HP1γ: 12417"
  },
  {
    "caption": "D. RNAchIP  read density per kb on the indicated introns for input and  IP in samples from both untreated and  PMA stimulated cells, n=6 biological replicates, or 3-times randomized intervals, n=18 samples. Dots represent individual data points. HP1γ/KO introns are all 272 intronic intervals between exon junctions  differentially detected in HP1γ  and KO. Random introns are a matching library of random intronic intervals. E.  RNAchIP read density per kb on the genes corresponding to the introns tested in (D), and analyzed as in (D), n=6 biological replicates, or 3-times randomized intervals, n=18 samples. Data information: All graphes represent mean and s.d. (** P < 0.005, ***P < 0.001; two-tailed Student's t-test).",
    "ncbi_link": "HP1γ: 12417"
  },
  {
    "caption": "B. RT-PCR analysis of the RNAs produced in the  splicing assay with the Prl3 wt or Prl3 CAmut constructs as depicted in A transfected into HP1γ or KO cell lines. The top 210bp and bottom 120bp amplicons correspond to the included form (beta globin with Prl  exon, more included in lane1, blue arrow, compared to lane 2), and the skipped form (beta globin exons only) of  RNA, respectively. Orange arrowheads, position of the HBGEX-F and HBGEX-R primers used in PCR analysis. C. Histogram showing the loss of inclusion of the Prl3 exon upon depletion of  HP1γ (in KO) relative to inclusion in the presence of HP1γ with the Prl3 wt (red) or Prl3 CA mut (grey) reporters. Based on the quantitation of 4 experiments as the one depicted in B. Values represent the fold change relative to HP1γ as a reference (dashed line). Graph represents mean and s.d. (*** P < 0.001; two-tailed Student's t-test; n=4). ",
    "ncbi_link": "HP1γ: 12417
beta globin: 3043
Prl3: 24683
Prl: 58937///53950///691552///266782///24282///24283"
  },
  {
    "caption": "(A-B) Spinal cord sections from 5-month-old WT and Tmem106b-/- mice were stained with anti- neurofascin, anti- LAMP1 and anti-Cath D antibodies. Accumulation of LAMP1 and CathD positive vacuoles at the distal end of AIS was observed in Tmem106b-/- motor neurons. Representative images from three independent mice were shown. Scale bar = 10 µm. n=3. Data presented as mean ± SEM. Unpaired Student's t test. ****, p<0.0001.",
    "ncbi_link": "Tmem106b: 71900"
  },
  {
    "caption": "(C-F) Western blot analysis of p62, ubiquitin (Ub), TDP-43 and p-TDP-43 in RIPA- and urea-soluble fractions from brain (C and E) and spinal cord (D and F) of 16-month-old WT and Tmem106b-/- mice. n=5. Data presented as mean ± SEM. Unpaired Student's t test. *, p<0.05, ***, p<0.001, ****, p<0.0001.",
    "ncbi_link": "Tmem106b: 71900"
  },
  {
    "caption": "(A) Tmem106b-/-Grn-/- mice do not show any changes in body weight. Body weight of 5-month-old mice of indicated genotypes were measured and analyzed. n=6-10.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(B Tmem106b-/-Grn-/- mice show reduced activities in the open field test. 4.5-month-old mice were used in the study.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "C) Tmem106b-/-Grn-/- mice show reduced activities in the open field test. 4.5-month-old mice were used in the study. Total movement was quantified. n=8-10. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(D Tmem106b-/-Grn-/- mice show abnormal hindlimb clasping behavior. 5-month-old mice were used in the study.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "E) Tmem106b-/-Grn-/- mice show abnormal hindlimb clasping behavior. 5-month-old mice were used in the study. Severity score was quantified. n= 8-10. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ***, p<0.001, ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A-D) Western blot analysis of NeuN, PSD95, SYN, GFAP, TMEM106B, PGRN and GAPDH in spinal cord (C5-C8) (A, B) and brain (C, D) lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(C Increase in apoptosis in Grn-/- and Tmem106b-/-Grn-/- retina as indicated by TUNEL assay. TUNEL positive signals per section were quantified. Data information: ONL: outer nuclear layer; INL: Inner nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; GCL: ganglion cell layer.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "D) Increase in apoptosis in Grn-/- and Tmem106b-/-Grn-/- retina as indicated by TUNEL assay. TUNEL positive signals per section were quantified.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(E Increase in Müller glial activation in Tmem106b-/-Grn-/- retina as indicated by GFAP staining. GFAP intensity per section was quantified and normalized to WT control. Data information: ONL: outer nuclear layer; INL: Inner nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; GCL: ganglion cell layer.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "F) Increase in Müller glial activation in Tmem106b-/-Grn-/- retina as indicated by GFAP staining. GFAP intensity per section was quantified and normalized to WT control.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(G, H) Increase in microglia activation in Grn-/- and Tmem106b-/-Grn-/- retina as indicated by IBA1 staining. The number of IBA1 positive cells per section was quantified. Data information: ONL: outer nuclear layer; INL: Inner nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; GCL: ganglion cell layer.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A Heatmap illustrating gene expression changes in WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- cortex samples isolated from 2.7-month-old mice. n=3. Genes with FDR p≤0.05, LogFC≥0.5 or ≤0.5 between WT and Tmem106b-/-Grn-/- groups are plotted based on hierarchical clustering analysis. Data information: Inflammation genes are highlighted in magenta and lysosomal genes are highlighted in blue.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "B) Heatmap illustrating gene expression changes in WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- spinal cord samples isolated from 2.7-month-old mice. n=3. Genes with FDR p≤0.05, LogFC≥0.5 or ≤0.5 between WT and Tmem106b-/-Grn-/- groups are plotted based on hierarchical clustering analysis. Data information: Inflammation genes are highlighted in magenta and lysosomal genes are highlighted in blue.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(C) Heatmap illustrating gene expression changes in the inflammation and lysosome pathways in WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- spinal cord samples. Data information: Inflammation genes are highlighted in magenta and lysosomal genes are highlighted in blue.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Western blot analysis of Galectin-3 and GPNMB in the spinal cord lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ***, p<0.001, ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Western blot analysis of Galectin-3 and GPNMB in the brain lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ***, p<0.001, ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(E) Immunostaining of Galectin-3, CathD and CD68 in spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Scale bar = 10 µm.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "TMEM106B and PGRN deletion results in increased autofluorescence in the spinal cord of 5-month-old mice. n=3. Scale bar = 10 µm.",
    "ncbi_link": "PGRN: 14824
TMEM106B: 71900"
  },
  {
    "caption": "TMEM106B and PGRN deletion results in increased autofluorescence in the thalamus of 5-month-old mice. n=3. Scale bar = 10 µm.",
    "ncbi_link": "PGRN: 14824
TMEM106B: 71900"
  },
  {
    "caption": "(G, H) Western blot analysis of lysosomal proteins in the spinal cord lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Asterisk indicates non-specific bands. n=3.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A) Spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/- and Tmem106b-/-Grn-/- mice were stained with anti-neurofascin, anti-LAMP1 and anti-CathD antibodies. Representative images from three independent mice were shown. Scale bar = 10 µm. (B) Quantification of LAMP1 positive vacuoles (> 2 µm) for experiments in (A). 4-6 sections/spinal cord from 3 mice were analyzed for each genotype. Data presented as mean ± SEM. Unpaired Student's t test: ****, p<0.0001. ",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A Immunostaining of GFAP with LAMP1 and Cath D in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Scale bar = 5 µm.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "B) Immunostaining of IBA1 with LAMP1 and Cath D in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Scale bar = 5 µm.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A) Accumulation of autophagosomes and lysosomes in the spinal cord sections from a 5-month-old Tmem106b-/-Grn-/- mouse as shown by transmission electron microscope analysis. Scale bar = 1µm. Arrows: autophagosome; arrow heads: lysosomes; (a): axon.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(B) Accumulation of myelin debris and amorphous inclusions in the microglia in the spinal cord sections from a 5-month-old Tmem106b-/-Grn-/- mouse as shown by transmission electron microscope analysis. Scale bar = 1µm. Arrows: myelin debris; arrow heads: dark amorphous inclusions; (m): microglia.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(C) Western blot analysis of LC3-I and LC3-II in the spinal cord lysates from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(D Immunostaining of TFE3 and IBA1 in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "E) Immunostaining of TFE3 and IBA1 in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Nuclear signals of TFE3 in IBA1 positive microglia were quantified. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ***, p<0.001, ****, p<0.0001. Scale bar = 10 µm.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(A, B) Western blot analysis of p62, ubiquitin (Ub), TDP-43 and p-TDP-43 in RIPA- and urea-soluble fractions from spinal cord (C5-C8) and brain of 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. Spinal cord: n=3; brain: n=4. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: *, p<0.05; **, p<0.01***, p<0.001, ****, p<0.0001.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "(C, D) Immunostaining of p62 and ubiquitin in the spinal cord sections from 5-month-old WT, Tmem106b-/-, Grn-/-, and Tmem106b-/-Grn-/- mice. The number of p62 or Ub positive puncta was quantified. n=3. Data presented as mean ± SEM. One-way ANOVA tests with Bonferroni's multiple comparisons: ***, p<0.001, ****, p<0.0001. Scale bar = 10 µm.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "a, Images show the localisation of endogeneous  SEPT2 and SEPT7 in RPE1 ARLB13B-mRuby2  cells with basal body staining. The insets to the right show enlargements of the cilium. Scale bar: 4µm (large) and 2µm (small). b, STED microscopy images showing ciliated RPE1  cells expressing EGFP-SEPT2 or SEPT7-EGFP and stained for ARL13B. Scale bar: 1µm.",
    "ncbi_link": "mRuby2: 
ARLB13B: 200894"
  },
  {
    "caption": "g, Electron microscopy of RPE1 WT and SEPT2-KO  cilia. Black arrows point to the  axoneme and basal body  (BB). Scale bar: 400nm. h, Quantification of (g). Only cilia  detected from bottom (BB) to  tip in serial sections were quantified. N>15 cilia from two independent experiments. Data include mean ±s.d.; P values are calculated by unpaired Wilcoxon-Mann-Whitney Rank Sum Test",
    "ncbi_link": "SEPT2: 4735"
  },
  {
    "caption": "i-j, RPE1 WT and SEPT2-KO cells after 48h SS were treated with solvent control (DMSO), cytochalasin D (CytoD) and/or nocodazole  (Noco) for 3h before  immunostaining  with the indicated antibodies. Representative images (i) and quantifications of  PS  (Glu tub) and whole cilia (ARL13B) length (j) are shown. The numbers above the cartoons in (j) show the ratio of the calculated DS/whole cilia length. Scale bar: 3µm. Three biological replicates, n=100  cilia per sample and repetition. Data show include mean ±s.d.; P values are calculated by two-tailed unpaired student t-test",
    "ncbi_link": "SEPT2: 4735"
  },
  {
    "caption": "e-f, RPE1 WT and SEPT2-KO cells were treated with control or KIF7  siRNA after 48h SS  and  immunostained with the indicated antibodies. Representative images (e) and quantifications of proximal segment  (Glu tub) and whole  cilia (ARL13B) length (f) are shown. The numbers above the cartoons in (f) show the ratio of the calculated  distal segments /whole  cilia length. Three biological replicates, n=100  cilia per sample and repetition. Scale bar: 2µm. Data include mean ±s.d. and P values are calculated by two-tailed unpaired student t-test.",
    "ncbi_link": "KIF7: 374654
SEPT2: 4735"
  },
  {
    "caption": "d, FRAP experiment of SSTR3-GFP in RPE1 WT and SEPT2 KO cells. Cells were starved for 48h before the beginning of inspection and imaged every 30sec for 10mins after bleaching. Scale bar: 5µm. e, Percentage of normalised  SSTR3-GFP signal recovery at whole cilia  after photobleching from (d). n=20  cilia are quantified from three biological replicates Data include mean ±s.d. and P values are calculated by two-tailed unpaired student t-test.",
    "ncbi_link": "SEPT2: 4735"
  },
  {
    "caption": "f-g, Influence of MKS3  depletion on  cilia length of  RPE WT and SEPT2-KO cells. Cells are treated with the indicated siRNA and  serum starved (SS) for 48h before  immunostaining  with the indicated antibodies. Representative images (f) and quantifications of proximal segment  (Glu tub) and whole cilia (ARL13B) length (g) are shown. The numbers above the cartoons in (g) show the ratio of the calculated distal segments/whole cilia  length. Scale bar: 2µm. Three 3 biological replicates, n=100 cilia per sample and repetition. Data include mean ±s.d. and P values are calculated by two-tailed unpaired student t-test.",
    "ncbi_link": "SEPT2: 4735
MKS3: 91147"
  },
  {
    "caption": "h-i, A functional TZ  is required for  KIF7 cilia tip localisation in RPE1  cells. KIF7  signal intensities are measured in ciliated RPE1 cells treated with control or MKS3 siRNA and 48h SS. Representative images (h) and quantification of  KIF7  signal intensity at the  base and tip of cilia  (h) are shown. Scale bar: 2µm. Three biological replicates, at least 60  cilia per sample and repetition. Data include mean ±s.d. and P values are calculated by two-tailed unpaired student t-test.",
    "ncbi_link": "MKS3: 91147"
  },
  {
    "caption": "a,  Time-lapse images of RPE1 WT and SEPT2-KO cells stably expressing ARL13B-GFP and γ-tubulin-mRuby2. Cells are starved for 32h before the beginning of inspection and imaged every 15min for 9.5h. Scale bar: 5µm. b, Quantification of (a) showing changes in  cilia  length during  time-lapse imaging. Three biological replicates, 10 cilia  per sample and repetition. c, Time-lapse images show ectocytosis  events observed in RPE1 SEPT2-KO cells. Experiments are done as in (a) with exception that cells are imaged every 15min. Scale bar: 2.5µm.",
    "ncbi_link": "SEPT2: 4735"
  },
  {
    "caption": "g-h, RPE1 SEPT2-KO cells expressing  ARL13B-mRuby2 and Neongreen-EFHC1 after 48h SS and immunostained  with Glu-tub antibody. Representative images (g) and quantifications of  proximal segment (Glu tub), EFHC1  and whole cilia (ARL13B) length (h) are shown. Three biological replicates, n=100  cilia per sample and repetition. Scale bar: 2µm.",
    "ncbi_link": "SEPT2: 4735"
  },
  {
    "caption": "Gel shift assay of biotin-labeled mascRNA and 5S rRNA with the cytosol (Cyto) and the postnuclear membrane lysate (Mem).",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "Northern blotting of mascRNA (top panel) and western blotting of β-Tubulin and Mortalin (bottom two panels) in the cytosolic fractions and the postnuclear membrane fractions of HEK293 and HepG2 cells.",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "SDS-PAGE analysis and coomassie staining of the proteins in the RNA pulldown samples. Biotin-labeled mascRNA (S) and the antisense RNA (AS) were used to pull down the RNA-protein complexes.   Representive data of mass spectrometry analysis of the RNA pulldown samples. Proteins most enriched in mascRNA (S) RNA pulldown sample are listed.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Western blots of the proteins in mascRNA S and AS pulldown samples (top 4 panels), and mascRNA and menRNA pulldown samples (Bottom 2 panels). β-tubulin was used as a loading control.",
    "ncbi_link": "menRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "RT-PCR analysis of RNAs extracted from ARS immunoprecipitation (RIP) samples (erro bars: mean ± SD; biological replicates n = 3). Eight complex-forming ARSs (DARS, EPRS, IARS, KARS, LARS, MARS, QARS and RARS) and GARS tagged with FLAG were overexpressed in HEK cells. ARS-RNA complexes were imminoprecipitated with anti-FLAG Magnetic Beads. The cell line constructed with PQCXIP vector (PQ) was used as a negative control. GAPDH was used as an internal control for qRT-PCR.",
    "ncbi_link": "GAPDH: 
FLAG: 
DARS: 1615
EPRS: 2058
GARS: 2617
IARS: 3376
KARS: 3735
LARS: 51520
MARS: 4141
QARS: 5859
RARS: 5917"
  },
  {
    "caption": "Northern blot validation of mascRNA in the RIP samples. 5S rRNA from the RIP samples was used as an internal control.",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "Gel shift assay of biotin-labeled mascRNA with the cytosol in the presence or the absence of a QARS antibody.",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Biotin-labeled mascRNA (sense (S) and antisense (AS)) and the acceptor stem mutants (Mut1-8) were used to pulldown the RNA-protein complexes. Top panel: western blotting of QARS in the pulldown samples. β-Tubulin was used as an cytosolic input control for the pulldown. Bottom panel: Biotin detection of the biotin-labeled mascRNA and the mutants.   Biotin-labeled mascRNA (sense (S) and antisense (AS)) and the anticodon stem-loop mutants (Anti-Mut1-9) were used to pulldown the RNA-protein complexes. Top panel: western blotting of QARS in the pulldown samples. β-Tubulin was used as an cytosolic input control for the pulldown. Bottom panel: Biotin detection of the biotin-labeled mascRNA and the mutants.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Gel shift assay of biotin-labeled mascRNA or the mutants (Anti-Mut1 and Mut1) with the cytosol.",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Northern blot analysis of mascRNA in mascRNA overexpressing HEK cells (mascRNA) and the cells expressing the scrambled RNA (Scramble). 5S rRNA was used as an internal control.",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "qRT-PCR analysis of MALAT1 (total RNAs used as templates) in mascRNA overexpressing (mascRNA) and the scrambled RNA expressing (Scramble) cells.",
    "ncbi_link": "MALAT1: 378938
mascRNA: 109136578"
  },
  {
    "caption": "Detection of the newly synthesized proteins in HEK cells stably expressing mascRNA (mascRNA) or the scrambled RNA (Scramble). Left: biotin detection of the labeled nascent proteins; right: coomassie staining of total proteins.   Quantification of the levels of the labeled nascent proteins in Panel C .   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Northern blot analysis of mascRNA in HEK cells transiently transfected with in vitro synthesized eGFP RNA fragment or mascRNA. 5S rRNA was used as an internal control.",
    "ncbi_link": "5S rRNA: 
eGFP: 
mascRNA: 109136578"
  },
  {
    "caption": "Detection of the newly synthesized proteins in HEK cells transiently transfected with in vitro synthesized eGFP RNA fragment or mascRNA. Left: biotin detection of the labeled nascent proteins; right: coomassie staining of total proteins.   Quantification of the levels of the labeled nascent proteins in Panel F.   ",
    "ncbi_link": "eGFP: 
mascRNA: 109136578"
  },
  {
    "caption": "Northern blot analysis of mascRNA in mascRNA overexpressing (mascRNA), and the mutants (Anti-Mut1 and Mut1) or the scrambled RNA (Scramble) expressing HEK cells. 5S rRNA was used as an internal control.",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "Detection of the newly synthesized proteins in HEK cells stably expressing mascRNA (mascRNA), the mutants (Anti-Mut1 and Mut1) or the scrambled RNA (Scramble). Left: biotin detection of the labeled nascent proteins; right: coomassie staining of total proteins.   Quantification of the levels of the labeled nascent proteins in Panel I.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Decay of the pulse Biotin-labeled proteins in HEK cells stably expressing mascRNA (mascRNA) or the scrambed RNA (Scramble)",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Western blot detection of ARS proteins in mascRNA overexpressing (mascRNA) or the scrambled RNA expressing (Scramble) cells. β-Tubulin was used as a loading control.   Quantification of the protein levels in Panel A.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Western blot detection of ARS proteins in HEK cells stably expressing mascRNA (mascRNA), the mutants (Anti-Mut1 and Mut1) or the scrambled RNA (Scramble). β-Tubulin was used as a loading control.",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Western blot detection of ARS proteins in HEK cells stably expressing mascRNA (mascRNA), the mutants (Anti-Mut1 and Mut1) or the scrambled RNA (Scramble). β-Tubulin was used as a loading control. Quantification of the protein levels in Panel C.",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "qRT-PCR analysis of MALAT1 RNA levels in MALAT1 knockdown and the control cells.",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": "Northern blot analysis of mascRNA in MALAT1 knockdown and the control cells. 5S rRNA was used as an internal control.",
    "ncbi_link": "5S rRNA: 
MALAT1: 378938
mascRNA: 109136578"
  },
  {
    "caption": "Western blot detection of ARS proteins in MALAT1 knockdown and the control cells.   Quantification of the protein levels in Panel G.   ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": "qRT-PCR analysis of GARS and QARS mRNAs in mascRNA overexpressing (mascRNA) or the scrambled RNA expressing (Scramble) cells.",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Western blot detection of ARS proteins in mascRNA overexpressing (mascRNA) or the scrambled RNA expressing (Scramble) cells, before and after emetine and cycloheximide treatment. β-Tubulin was used as a loading control.   Quantification of the relative QARS protein levels in Panel J.   Quantification of the relative GARS protein levels in Panel J.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Western blot detection of endogenous and FLAG-tagged ARS proteins in HEK cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. β-Tubulin was used as a loading control.",
    "ncbi_link": "GARS: 2617
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in HEK cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.   Quantification of the labeled nascent protein levels in Panel B.   ",
    "ncbi_link": "GARS: 2617
QARS: 5859"
  },
  {
    "caption": "Western blot detection of FLAG-tagged ARS proteins in mascRNA overexpressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. β-Tubulin was used as a loading control.",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in mascRNA overexpressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.   Quantification of the labeled nascent protein levels in Panel E.   ",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Western blot detection of FLAG-tagged ARS proteins in mascRNA anticodon stem-loop mutant Anti-Mut1 expressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. β-Tubulin was used as a loading control.",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in mascRNA Anti-Mut1 expressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in mascRNA Anti-Mut1 expressing cells transiently transfected with PQCXIP vector (PQ), QARS expressing (QARS) or GARS expressing (GARS) plasmid. Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins. Quantification of the labeled nascent protein levels in Panel H.",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Western blot detection of FLAG-tagged ARS proteins in MALAT1 knockdown cells with stable QARS (QARS) or GARS (GARS) overexpression or without (PQ). β-Tubulin was used as a loading control.",
    "ncbi_link": "GARS: 2617
MALAT1: 378938
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in wild-type HEK cells (WT) and MALAT1 knockdown cells (sh-MALAT1), or MALAT1 knockdown cells with stable QARS (QARS) or GARS (GARS) overexpression or without (PQ). Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.",
    "ncbi_link": "GARS: 2617
MALAT1: 378938
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in wild-type HEK cells (WT) and MALAT1 knockdown cells (sh-MALAT1), or MALAT1 knockdown cells with stable QARS (QARS) or GARS (GARS) overexpression or without (PQ). Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins. Quantification of the labeled nascent protein levels in Panel K.",
    "ncbi_link": "GARS: 2617
MALAT1: 378938
QARS: 5859"
  },
  {
    "caption": "Detection of the newly synthesized proteins in QARS (shQARS) or GARS (shGARS) knockdown cells and the control cells stably overexpressing mascRNA (mascRNA) or expressing the scrambled RNA (Scramble). Left, biotin detection of the labeled nascent proteins; right, coomassie staining of total proteins.   Quantification of the labeled nascent protein levels in Panel M.   ",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Northern blotting of mascRNA and 5S rRNA in the lysates of HEK cells before and after FBS starvation.",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "Northern blotting of mascRNA and 5S rRNA in the lysates of human embryonic stem cells on different days of differentiation.",
    "ncbi_link": "5S rRNA: 
mascRNA: 109136578"
  },
  {
    "caption": "Soft agar colony formation assay of HEK, HeLa or MCF-7 cells overexpressing mascRNA or expressing the the scrambled RNA.   Quantification of stained colones in Panel C.   ",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Soft agar colony formation assay of HEK cells overexpressing mascRNA, or expressing the mutants (Anti-Mut1 and Mut1) or the the scrambled RNA (Scramble).",
    "ncbi_link": "mascRNA: 109136578"
  },
  {
    "caption": "Soft agar colony formation assay of QARS (shQARS) or GARS (shGARS) knockdown cells and the control cells stably overexpressing mascRNA (mascRNA) or expressing the the scrambled RNA (Scramble).",
    "ncbi_link": "GARS: 2617
mascRNA: 109136578
QARS: 5859"
  },
  {
    "caption": "Soft agar colony formation assay of MALAT1 knockdown cells (shMALAT1) and the control cells (Control) with stable QARS (QARS) or GARS (GARS) overexpression or without (PQ).",
    "ncbi_link": "GARS: 2617
MALAT1: 378938
QARS: 5859"
  },
  {
    "caption": "(A) The graphs depict the  Aβ  profiles generated by WT or mutant PSEN1 MEF  cell lines transduced with adenovirus  encoding APPC99. ELISA  quantified secreted Aβ37, Aβ38, Aβ40  and Aβ42  peptide levels are shown as % of total Aβ  (sum of the four peptides). The blue, orange, green and purple dotted lines indicate the levels of Aβ37, Aβ38, Aβ40  and Aβ42  peptides in the WT Aβ  profile, respectively. Data are presented as mean ± SD, N ≥ 3 independent experiments.",
    "ncbi_link": "APP: 351
PSEN1: 5663"
  },
  {
    "caption": "(B) GSEC processivity levels for the cleavage of APPC99 determined in WT and mutant PSEN1/GSEC  cell lines. The mutant Aβ(37+38)/(40+42) ratios are shown as % of the WT cell line. Data presented as mean ± SD, N ≥ 3 independent experiments. As reference, a dotted line was drawn to indicate 10% (WT levels). One-way ANOVA followed by Dunnett's post-hoc test with comparison to WT was used to determine statistical significance (P < 0.05); **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "PSEN1: 5663"
  },
  {
    "caption": "(A)  Aβ profiles  generated by WT or mutant PSEN1 MEFs  lines treated with 1 µM GSM III. The chemical structure of the bicyclic heterocycle  GSM III  is depicted. Data are presented as mean ± SD, N ≥ 3 independent experiments. The blue, orange, green and purple dotted lines indicate the levels of Aβ37, Aβ38, Aβ40  and Aβ42  peptides in the WT  Aβ profile, respectively.",
    "ncbi_link": "PSEN1: 5663"
  },
  {
    "caption": "(D) Aβ profiles generated by WT or mutant PSEN1  cell lines overexpressing APPC99 and treated with increasing concentrations of GSM III. Data are presented as mean ± SD, N = 2 independent experiments.",
    "ncbi_link": "APP: 351
PSEN1: 5663"
  },
  {
    "caption": "Analysis of mutant APP  substrates with regards to their effects on the response of GSEC  to the imidazole-based GSM III. Aβ profiles secreted by HEK293T  cells transiently expressing WT or mutant APPC99 substrates in presence of vehicle (DMSO) or 1 µM GSM III were analysed by ELISA  (D) ELISA-based Aβ  profiles are presented as % of total Aβ  (Aβ37+ Aβ38+ Aβ40+ Aβ42) (mean ± SD, N ≥ 3); One-way ANOVA followed by Dunnett's post-hoc test with comparison to WT was used to determine statistical significance; ****P < 0.0001. F(DFn, DFd): F (4, 17) = 71.68.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Analysis of mutant APP  substrates with regards to their effects on the response of GSEC  to the imidazole-based GSM III. Aβ profiles secreted by HEK293T  cells transiently expressing WT or mutant APPC99 substrates in presence of vehicle (DMSO) or 1 µM GSM III were analysed by mass spectrometry (MS). (E) APP  mutation-driven effects on GSEC  processivity according to the Aβ(37+38)/(40+42) ratio are presented as % of the WT condition (mean ± SD). One-way ANOVA followed by Dunnett's post-hoc test with comparison to WT was used to determine statistical significance; ****P < 0.0001. F(DFn, DFd): F (4, 17) = 71.68.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(B) Aβ profiles generated by WT or mutant PSEN1  cell lines transduced with APPC99. Dotted lines indicate the levels of Aβ  peptides (%) in WT profiles. Data presented as mean ± SD, N ≥ 3 independent experiments.",
    "ncbi_link": "APP: 351
PSEN1: 5663"
  },
  {
    "caption": "(C) Pocket filling PSEN1  V236W and Y106W-V236W substitutions lead to increased Aβ(37+38)/(40+42) ratio, indicating the activation of the sequential GSEC-mediated cleavage of  APPC99. Data presented as mean ± SD, N ≥ 3 independent experiments.",
    "ncbi_link": "PSEN1: 5663"
  },
  {
    "caption": "(D)  Aβ profile  analysis in  dose-response experiments for  GSM III revealed no modulation of the PSEN1  V236W mutant cell line. Data are presented as mean ± SD, N = 2 independent experiments. For comparison purposes, WT and V236W mutant Aβ profiles are presented in panel 6B.",
    "ncbi_link": "PSEN1: 5663"
  },
  {
    "caption": "(E) GSEC  activity  assay using purified GSEC  and an APP-based fluorogenic peptide as substrate Upper panel: In the non-cleaved state the Dpn  (2,4-dinitrophenyl) quencher group suppresses fluorescent emission from the Nma  (N-methyl-o-aminobenzoic acid) fluorophore through  Förster resonance energy transfer (FRET). Upon GSEC  cleavage, the Nma  group emits at λ = 430 nm a fluorescent signal upon excitation at λ = 355 nm. Lower panel: Specific activities for the purified WT or mutant GSECs   (bearing the indicated substitutions in PSEN1) treated with DMSO  (vehicle), 10 µM GSMIII or GSM II. Data are normalized to the WT GSEC  activity in DMSO  (vehicle). Data are shown as mean ± SD, N ≥ 3 independent experiments. Significance is shown for meaningful comparisons; two-way ANOVA with comparison to WT was used to determine statistical significance; **P < 0.01, ***P < 0.001, ****P < 0.0001, ns: not significant.",
    "ncbi_link": "APP: 351
PSEN1: 5663"
  },
  {
    "caption": "(F) Transition state analogue inhibitor  L-685,458 (Inhibitor X) treatment of WT, V236W or Y240W mutant PSEN1  cell lines. Inhibitory profiles  and derived IC50 values (table) indicate that the PSEN1-V236W significantly increases the affinity for the inhibitor. Dotted line indicates 50% inhibition. Data presented as mean ± SD, N = 3 independent experiments.",
    "ncbi_link": "PSEN1: 5663"
  },
  {
    "caption": "A, A targeted MAPPIT screen identifies several DUBs as putative RAS interactors. A MAPPIT array containing DUB prey library was screened with HRAS G12V as bait. pSEL(+2L)-HRAS G12V was expressed in HEK293T cells together with the indicated prey. BRAF served as a positive control. Each measurement was done in triplicate. The results are expressed as a mean of normalized luciferase activity (leptin-treated cells vs leptin-untreated cells). The overall mean value + 2 s.d. served as a threshold.",
    "ncbi_link": "BRAF: 673
HRAS: 3265
RAS: 3265"
  },
  {
    "caption": "B, MAPPIT assay confirms the interaction between OTUB1 and RAS proteins. pSEL(+2L) vectors coding RAS proteins were expressed in HEK293T cells together with the indicated prey. Empty vector and two random baits, MAL and eDHFR, were used as negative controls. REM2 and EFHA1 preys that bind to the bait receptor itself was used to evaluate expression of the RAS baits. The results are expressed as a mean of normalized luciferase activity ± s.e.m (leptin-treated cells vs leptin-untreated cells), n=3.",
    "ncbi_link": "eDHFR: 1719
RAS: 3265
MAL: 4118
EFHA1: 221154
REM2: 161253"
  },
  {
    "caption": "C, NRAS Q61K mutant co-immunoprecipitates with OTUB1. At 48 hours post-transfection with Flag-tagged NRAS Q61K and HA-tagged OTUB1 expression constructs, HA-tagged OTUB1 was immunoprecipitated with anti-HA-agarose followed by immunoblotting using anti-Flag or anti-HA antibodies.",
    "ncbi_link": "NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "D, OTUB1 interacts with wt NRAS and active NRAS mutant. Flag-tagged NRAS proteins were immunoprecipitated using anti-Flag (M2) agarose from HEK293T cells overexpressing HA-tagged OTUB1 or empty vector (V).",
    "ncbi_link": "NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "E, GTP binding does not affect the complex formation between NRAS and OTUB1. Recombinant Flag-tagged NRAS was incubated with lysates derived from HEK293T cells expressing HA-tagged OTUB1 in the excess of GTP-γ-S or GDP, followed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "F, OTUB1 interacts with wt KRAS. Flag-tagged KRAS was immunoprecipitated using anti-Flag (M2) agarose from HEK293T cells overexpressing HA-tagged OTUB1 or empty vector (V). C, D, E, F, Immunoprecipitates, IP. Whole cell lysate, WCL.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "G, OTUB1 co-localizes with KRAS at the plasmamembrane. At 24 hours after co-transfection with GFP-tagged KRAS and HA-tagged OTUB1, HeLa cells were immunostained with anti-HA antibody. The outlined areas are shown at higher magnification at the top of each image. Scale bar, 10 micron.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "A, Suppression of OTUB1 expression increases NRAS mono- and di-ubiquitination. 6xHis-tagged ubiquitin and Flag-NRAS were introduced into HEK293T cells expressing shGFP or shRNAs against OTUB1. Ubiquitinated NRAS was purified by Co2+ metal affinity chromatography and detected by anti-Flag antibody.",
    "ncbi_link": "GFP: 
NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "B, C, D, Catalytic activity of OTUB1 is not required to inhibit RAS ubiquitination. 6xHis-tagged ubiquitin and RAS expression constructs were introduced into HEK293T cells expressing wt HA-OTUB1, the catalytically dead mutant HA-OTUB1 C91S, or empty vector (V). Ubiquitinated RAS was purified by Co2+ metal affinity chromatography and detected by anti-Flag antibody.",
    "ncbi_link": "RAS: 3265
OTUB1: 55611"
  },
  {
    "caption": "E, OTUB1 induces membrane RAS re-localization. Confocal imaging of HeLa cells expressing the indicated constructs. For each sample, z-stacks obtained by scanning the sample from the apical to the basal layer. Step-size, 2 micron.",
    "ncbi_link": "RAS: 3265"
  },
  {
    "caption": "A, B, OTUB1 overexpression promotes serum-induced activation of endogenous wt RAS (A) or wt NRAS (B). GTP-bound RAS was pulled down from HEK293T cells expressing HA-tagged OTUB1 or empty vector (V) using recombinant RAF1 RBD conjugated to agarose beads. Input was controlled by immunoblotting using anti-panRAS or anti-Flag antibodies",
    "ncbi_link": "RAS: 3265
NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "C, D OTUB1 enhances serum-induced ERK1/2 phosphorylation in endogenous wt RAS (C) or wt KRAS (D). Levels of phosphorylated ERK1/2 and total ERK1/2 in HEK293T cells expressing HA-tagged OTUB1 or empty vector (V) were analyzed by Meso Scale assay. The results are expressed as a mean of pERK1/2 levels relative to total ERK1/2 ± s.e.m. n=2.",
    "ncbi_link": "RAS: 3265
KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": " . E, F, Overexpression of wt OTUB1 (E) or the catalytically dead mutant OTUB1 C91S mutant (F) promotes serum-induced MAPK activation in cell expressing wt NRAS. Whole cell lysates were analyzed by immunoblotting using the indicated antibodies. ",
    "ncbi_link": "NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "G, H, Overexpression of OTUB1 has no effect on serum-induced MAPK activation in cell expressing mutant NRAS Q61K or KRAS G12V. Whole cell lysates were analyzed by immunoblotting using antibodies as indicated. A,B,C,D,E,F,G,H Serum-starved HEK293T cells expressing the indicated constructs were stimulated with 10% serum for the indicated time periods.",
    "ncbi_link": "KRAS: 3845
NRAS: 4893
OTUB1: 55611"
  },
  {
    "caption": "I, Immunoblot of OTUB1 overexpression in immortalized human embryonic kidney epithelial cells (HEK TEST), expressing empty vector (V), myristoylated AKT1 (myr-AKT), MEK1 D218,D222 mutant (MEKDD).",
    "ncbi_link": "AKT: 207
AKT1: 207
MEK1: 5604"
  },
  {
    "caption": "J, K, OTUB1 cooperates with active AKT1 to promote anchorage-independent growth. Representative images of soft-agar colonies formed by HEK TEST cells expressing the indicated constructs. The number of soft agar colonies formed by cells expressing OTUB1 compared to cells expressing an empty vector. Data are presented as mean ± s.e.m. p-values were determined by two-sided t-Test, n=2.",
    "ncbi_link": "AKT1: 207
OTUB1: 55611"
  },
  {
    "caption": "B,C, OTUB1 overexpression in TCGA lung carcinomas is associated with 11q13.1 copy number alteration. Pearson correlation of OTUB1 copy number (log2 ratio) with OTUB1 mRNA levels (RNAseq normalized read counts, log2 transformed) was analyzed.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "D,E,F, OTUB1 expression in TCGA lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (SCC) patients. Patients were stratified according to their OTUB1 mRNA levels and/or their KRAS status as described in Materials and Methods. Box whisker plots represent OTUB1 mRNA expression levels in TCGA lung carcinoma patients determined by RNAseq analysis. p-values were determined by two-sided t-Test. Total number of patients, n.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "G, Gain of 11q13.1 locus is an early event in lung adenocarcinoma development. TCGA lung adenocarcinoma patients with diploid or gain of the OTUB1 locus were stratified according tumor stages (T1-T4). Total numbers of patients, n. Statistical comparison of the sample distributions were compared using Chi-square test.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "H, OTUB1 mRNA overexpression is an early event in lung adenocarcinoma development. TCGA lung adenocarcinoma patients were stratified by tumor stages (T1-T4) and OTUB1 expression levels as described in Materials and Methods. Total numbers of patients, n. Statistical comparison of the sample distributions were compared using Chi-square test.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "I, KRAS mutation is a late event in lung adenocarcinoma progression. TCGA lung adenocarcinoma patients with different KRAS mutation status were stratified by tumor stages (T1-T4). Total numbers of patients, n. Statistical comparison of the sample distributions were compared using Chi-square test.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": ", Suppression of OTUB1 expression in NSCLC cell lines by specific shRNAs against OTUB1 was confirmed by immunoblotting using antibody against OTUB1.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "B, OTUB1 suppression decreases serum-induced ERK1/2 phosphorylation. Serum-starved A549 cells expressing shRNAs against OTUB1 or GFP were stimulated with 10% serum for the indicated time periods. Levels of phosphorylated ERK1/2 and total ERK1/2 were analyzed by Meso Scale assay. The results are expressed as a mean of pERK1/2 levels relative to total ERK1/2 ± s.e.m; p-values were determined by two-sided t-Test, n=2.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "C, D, OTUB1 suppression impairs the anchorage-independent growth of Western blot cancer cell lines. Representative images of soft-agar colonies formed by Western blot cells expressing shRNAs against OTUB1 or GFP. The number of soft agar colonies formed by cells expressing shOTUB1 compared to cells expressing shGFP. Data are presented as mean ± s.e.m. p-values were determined by two-sided t-Test, n=3.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "C, D, OTUB1 suppression impairs the anchorage-independent growth of lung cancer cell lines. Representative images of soft-agar colonies formed by lung cells expressing shRNAs against OTUB1 or GFP. The number of soft agar colonies formed by cells expressing shOTUB1 compared to cells expressing shGFP. Data are presented as mean ± s.e.m. p-values were determined by two-sided t-Test, n=3.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "E, Xenograft tumor growth of A549 cells expressing shRNAs against GFP or OTUB1 subcutaneously injected into nude mice. p-value was determined by 2-way ANOVA.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "A, OTUB1 overexpression promotes serum-induced MAPK activation in wt KRAS H1993 lung adenocarcinoma cells.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "B, OTUB1 overexpression does not affect serum-induced MAPK activation in mutant KRAS A549 lung adenocarcinoma cells. A,B, Serum-starved lung cells expressing Flag-OTUB1 or an empty vector (V) were stimulated with 10% serum for the indicated time periods. Whole cell lysates were analyzed by immunoblotting using antibodies against pERK1/2, ERK1/2, Flag and vinculin.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "C, Representative immunoblots of Flag-tagged OTUB1 overexpression in lung adenocarcinoma cell lines",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "D, E, OTUB1 overexpression affects anchorage-independent growth of lung adenocarcinoma cell lines. Representative images of soft-agar colonies formed by the indicated cells expressing Flag-OTUB1 or empty vector (V). The number of soft agar colonies formed by OTUB1 expressing cells compared to cells expressing an empty vector. Data are presented as mean ± s.e.m. p-values were determined by two-sided t-Test, n=3.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "D, E, OTUB1 overexpression affects anchorage-independent growth of lung adenocarcinoma cell lines. Representative images of soft-agar colonies formed by the indicated cells expressing Flag-OTUB1 or empty vector (V). The number of soft agar colonies formed by OTUB1 expressing cells compared to cells expressing an empty vector. Data are presented as mean ± s.e.m. p-values were determined by two-sided t-Test, n=3.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "F,G, Xenograft tumor growth of A549, H1993 or H1437 cells expressing Flag-OTUB1 or an empty vector (V) subcutaneously injected into nude mice. p-values were determined by 2-way ANOVA.",
    "ncbi_link": "OTUB1: 55611"
  },
  {
    "caption": "B, OTUB1 expression in lung non-small cell carcinomas with different KRAS mutation status. OTUB1 expression was assessed in TMA samples by IHC.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "E, OTUB1 levels correlates with increased levels of phosphorylated-ERK1/2 in wt KRAS lung adenocarcinomas. Association between OTUB1 and pERK1/2 expression levels was assessed in the same tumor samples by IHC.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "G, Wt KRAS lung adenocarcinoma TCGA patients with medium OTUB1 expression have poorer overall survival.",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": " H, OTUB1 expression levels are not associated with survival rate of KRAS-mutant lung adenocarcinoma TCGA patients. G,H, Patients were stratified according to their OTUB1 mRNA levels and/or their KRAS status as described in Materials and Methods. Overall survival of lung adenocarcinoma patients expressing different levels of OTUB1 mRNA as measured by Kaplan-Meier curves. p-values were determined by Log Rank Test. ",
    "ncbi_link": "KRAS: 3845
OTUB1: 55611"
  },
  {
    "caption": "(F-G) (F) NIH-3T3  cells were transiently transfected with either pEGFP or pEGFP-PPE2. After 24 hours of transfection, cells were fixed and observed under a confocal microscope. DAPI  was used to stain  the nucleus. (G) Nuclear localization  of rPPE2  was measured by calculating colocalization  coefficient. Data information: Data represent Mean ± SEM of more than 50 cells of three independent experiments. For Figure G, unpaired t-test was applied to calculate p values.",
    "ncbi_link": "EGFP: 
PPE2: 886684"
  },
  {
    "caption": "(E) Varying concentrations of rPPE2 protein were incubated with [γ-32P]-ATP  oligonucleotides of 60 bp spanning SCF  promoter.  DNA-protein  complexes were resolved on 7% native polyacrylamide  gel. In cold  competition reactions, equimolar cold/unlabeled 60 bp oligonucleotides were used (arrow represents PPE2-oligo complex). The data shown are representative of 3 independent experiments.",
    "ncbi_link": "SCF: 17311"
  },
  {
    "caption": "(E) H4K20me1 (blue) and H3K27me3 (red) accumulation across the Xi after 12 h of DOX treatment. The black line is a locally estimated scatterplot smoothing (LOESS) regression on all 10-kb windows (dots). Below each plot shown is the Xist locus (green bar) and Xist entry sites (black bars).",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "(A) Genome browser tracks showing H3K27me3 (top) and H4K20me1 (bottom) accumulation at a gene silenced rapidly (Rnf12) or more slowly (Pgk1). Allele-specific tracks were overlaid (B6 in red and Cast in blue). Note strong H4K20me1 bi-allelic pre-marking at gene bodies.",
    "ncbi_link": "Pgk1: 18655
Rnf12: 19820"
  },
  {
    "caption": "(B) Representative image of IF/RNA FISH for Xist RNA and H4K20me1 in cells expressing XistFL or XistΔBC. Arrowheads point to the Xist RNA domains. Scale bar = 5 μm.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "(C) Graph represents the mean % +/- StDev of Xist RNA domains enriched for H4K20me1 (left) or H3K27me3 (right) in cells expressing XistWT or XistΔBC. Shown are averages from at least 2 independent experiments; minimum of 50 Xist RNA domains were counted per experiment; only P-values corresponding to significant differences from unpaired Student's t-test comparing mutants to Xist FL are indicated as * (P-value < 0.05). Data for H3K27me3 was extracted from published data (Bousard et al., 2019).",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "B Body  weight of Uqcrh -/- mice and wild-type littermates at 1-2 weeks (n = 5 to 10), during the post-weaning period from 5-6 weeks of age (n = 3 to 7) and weekly from 6 to 10 weeks (n = 13 to 66), data are shown as mean ± SD. **** p < 0.0001, 2-Way ANOVA, from 7.5wk of age  for Uqcrh-/- males  and  females versus sex-matched controls. Data are shown as single data points and median, or categorical data, males and  females pooled, since genotype-related effects were comparable for both sexes from different cohorts. * p < 0.05, *** p <0.001, Wilcoxon rank-sum test.",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "C, D Clinical chemistry plasma concentrations of parameters related to acid-base balance (Lactate and Ammonia) and metabolic state (Glucose) n = 15 Uqcrh-/- and 16 WT pups 1-2-week-old (C); n = 15 f, 15 m  Uqcrh-/- and 15 f,15 m WT mice aged 8-9 weeks (D); sex not differentiated. Data shown as scatter dot plots with line at median. * p < 0.05, ** p < 0.01, **** p < 0.0001, Wilcoxon rank sum test.",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "F Measures related to  behaviour  and  neurological function, data generated by the SHIRPA (9 weeks old, F), n = 7f, 8m Uqcrh-/- and 8f, 9m WT animals. Prepulse inhibition   of the acoustic startle as a parameter associated with sensorimotor gating (10 weeks, E right panel), n = 7 f/5 m Uqcrh-/- and 8 f/ 9 m WT mice. Sex is not differentiated. Data are shown as scatter dot plots with a line representing the median. *** p < 0.001, **** p < 0.0001, Wilcoxon rank-sum test.",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "G Parameters related to  heart  function generated by  Echocardiography (ECHO) and Electrocardiography  (ECG), n = 15 f, 15 m Uqcrh-/- and 15 f, 15 m WT mice, 6 weeks old.",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "A Respiratory chain  enzyme activities from  human control (green) and patient (red)  fibroblasts. Mean activities of controls (n = 8) are set to 100% and error bars represent 1 standard deviation. Data are normalised to citrate synthase (CS) activity. B Respiratory chain enzyme activities in  heart,  brain and  liver, of wild-type and  Uqcrh-/- mice. Data are normalised to  citrate synthase  (CS) activity. Values are given as mean ± SD, n = 4 WT, 5 Uqcrh-/- (Heart), 3 WT, 3 Uqcrh-/- (Brain), 1 WT and 2 Uqcrh-/- (Liver). * p < 0.05, **** p < 0.0001, 2-way ANOVA (Multiple comparison). ",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "F Immunohistochemical staining of UQCRC2 was performed on  liver,  heart and kidney derived from wild-type and Uqcrh-/- mice at 9 weeks of age. Staining of VDAC1/porin was also carried out G Graphs indicate score values of immunohistochemical staining intensity of both VDAC1/porin  and UQCRC2. Data are given as mean ± SEM. * p < 0.05; n = 3, Student's t-test (unpaired samples).",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "A  Western blot  analysis of control (n = 2, C1-2) and patient fibroblasts  transduced with a lentiviral vector (pLVX) containing wild-type UQCRH. Expression of wild-type UQCRH was induced using various concentrations of doxycycline (dox) up to 20 ng/ml for 72 hours. B BN-PAGE analysis of control (n = 2, C1-2) and  patient fibroblasts  transduced with a lentiviral vector (pLVX) containing wild-type UQCRH. Transduced fibroblasts were either uninduced or induced with 20 ng/ml doxycycline (dox) for 72 hours. ",
    "ncbi_link": "UQCRH: 7388"
  },
  {
    "caption": "C Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei  (DAPI, blue), in control (NHDF) fibroblasts. D Immunofluorescence for  UQCRC2 (green), VDAC1/porin (red) and  nuclei  (DAPI, blue), in patient fibroblasts. E Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and  nuclei  (DAPI, blue), in control (NHDF) fibroblasts  transduced with wild-type UQCRH. F Immunofluorescence  for UQCRC2 (green), VDAC1/porin (red) and  nuclei  (DAPI, blue), in  patient fibroblasts  transduced with wild-type (WT) UQCRH. G Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei  (DAPI, blue), in control (NHDF) fibroblasts transduced with the pseudogene UQCRHL. H Immunofluorescence for UQCRC2 (green), VDAC1/porin (red) and nuclei  (DAPI, blue), in patient fibroblasts transduced with the pseudogene UQCRHL. I Graph indicates the staining intensity of  UQCRC2 in control (NHDF) fibroblasts (green) and patient fibroblasts  (red), those respective cell lines transduced (T) with wild-type UQCRH (diagonal lines) and those cell lines transduced with the pseudogene UQCRHL (vertical lines) measured using Image J, Data are given as mean ± SEM. One-way ANOVA (Kruskal-Wallis test), * p < 0.05; n = 3 macroscopic field (10-14 cells for macroscopic field were measured). ",
    "ncbi_link": "UQCRH: 7388
UQCRHL: 440567"
  },
  {
    "caption": "heart tissue from wild-type (WT) and Uqcrh-/- mice  were solubilised with  digitonin and separated on native gradient gels. F BN-PAGE gel stained  with Coomassie (left) and NADH:NTB reductase activity stain  (right) showing molecular weight marker (BHM) and heart  tissue samples from wild-type (WT) and Uqcrh-/- mice. G BN-PAGE and immunoblot using the antibody to CIII  subunit UQCRC2 in heart  tissue samples from wild-type (WT) and Uqcrh-/- mice. H Further  complexome analysis of the BN-PAGE gels shown in F, shown here are average IBAQ values of subunits from complexes III, I and IV ",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "I Profile of complex III (averaged IBAQ values) in wild-type (+/+, solid line) and Uqcrh-/- (-/-, dashed line) heart  tissue. J Profile of complexes III (red), I (yellow) and IV (green) to visualise and assess supercomplex composition and stability in wild-type (+/+, solid line) and Uqcrh-/- (-/-, dashed line) heart tissue. ",
    "ncbi_link": "Uqcrh: 66576"
  },
  {
    "caption": "Flow cytometry analysis of H-2Kb surface expression on splenocytes derived from C57BL/6 wild type (left side) or LMP7-/- (right side) mice treated with vehicle (DMSO), ONX 0914 (300 nM), PRN1126 (300 nM), ML604440 (300 nM), LU-001i (300 nM), PRN1126+ML604440 (300 nM each), or PRN1126+LU-001i (300 nM each) overnight. Unstained splenocytes were used as negative control. Pooled data from three independent experiments (n=9) are shown as the means of median fluorescent intensity ± SEM. All data were statistically compared to the DMSO treated group. **P < 0.01, ***P < 0.001. One-way ANOVA.",
    "ncbi_link": "LMP7: 16913"
  },
  {
    "caption": "WT and SNX10 KO Caco-2 cells were treated with indicated doses of  OMVs  for 24h. Protein expression of E-cadherin and  SNX10 was determined by immunoblots (A) and quantified by ImageJ software (B) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "A, B WT and  SNX10 KO Caco-2 cells were treated with or without  OMVs (100 μg/mL) for 24 h. The fold changes in mRNA levels of SNAI1 (encoding Snail) (A) and SNAI2  (encoding  Slug) (B) in  Caco-2  cells were determined by RT-qPCR. n = 6 independent experiments. Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ns, not significant.",
    "ncbi_link": "SNAI1: 6615
Snail: 6615
SNAI2: 6591
Slug: 6591
SNX10: 29887"
  },
  {
    "caption": "C WT and SNX10 KO Caco-2  cells were treated with or without  OMVs (100 μg/mL) for 24 h. Cytoplasmic and nuclear proteins were extracted for Snail and Slug  determination by immunoblots.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "WT and  SNX10 KO Caco-2  cells were treated with or without OMVs  (100 μg/mL) for 24 h. quantified the percentage of  Snail (E) or Slug (F)-positive nuclei respectively. Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "H WT and SNX10  KO Caco-2  cells were transfected with  Ad-vector or  Ad-SNX10, followed by treatment with or without 100 μg/mL OMVs for 24 h. Proteins from nucleus,  cytoplasm and total cell lysates were subjected to immunoblots  with the indicated antibodies.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "C, D Levels of p-Lyn, Lyn,  E-cadherin and SNX10 in WT and SNX10 KO  Caco-2 cells treated with or without OMVs  (100 μg/mL) for 24h were determined by  immunoblots (C) and quantified by ImageJ software (D) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "E, F  Caco-2 cells were transfected with Ad-vector or Ad-SNX10, followed by treatment with or without  OMVs (100 μg/mL) for 24h. Lysates were extracted and subjected to immunoblots  with the indicated antibodies (E) and quantified by ImageJ software (F) (n = 3 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "I Cytoplasmic and  nuclear proteins were extracted from WT and  SNX10 KO  Caco-2 cells treated with or without Tolimidone (10 μM), and the indicated proteins were analyzed by  immunoblots.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "D WT and SNX10 KO Caco-2  cells were treated with or without  OMVs (100 μg/mL) for 24 h and then subjected to  IP  with anti-caspase-5 antibody.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "E Representative images of  co-staining of  Lyn and caspase-5 in WT and SNX10 KO Caco-2 cells treated with or without OMVs (100 μg/mL) for 24 h. Scale bar: 20 μm. F The  co-localization of  Lyn and caspase-5 was quantified by ImageJ software. n = 3 independent experiments, n = 18 fields analysed. Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001. ",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "H Lysates of Flag-tagged full-length SNX10 or its different truncated mutants transfected Caco-2 cells were subjected to immunoprecipitation.",
    "ncbi_link": "Flag: 
SNX10: 29887"
  },
  {
    "caption": "E, WT and SNX10 KO  Caco-2 cells were treated with  OMVs (100 μg/mL) for the indicated  time and  stained with antibodies against LPS  and Rab5 (E). Scale bar: 20 μm.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "G  LPS levels in the cell culture supernatants of WT and SNX10 KO Caco-2 cells stimulated by OMVs (100 μg/mL) for the indicated time were detected by  LAL assay (n = 6 independent experiments). H LPS levels in the  cytosolic and residual fractions of  Caco-2 cells stimulated by OMVs (100 μg/mL) with or without chloroquine (CQ) (200 nM) or bafilomycin A1 (Baf A1) (50 nM) for the indicated time were detected by LAL assay  (n = 6 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant. ",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "C WT and SNX10 KO Caco-2 cells were treated with or without OMVs (100 μg/mL) for 24h and then subjected to IP with anti-PIKfyve antibody.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "D, E  Co-staining of PIKfyve and caspase-5 in WT and  SNX10 KO  Caco-2  cells treated with or without  OMVs (100 μg/mL) for 24 h (D). Anti-PIKfyve and anti-caspase-5 antibodies were used to detect endogenous PIKfyve and caspase-5 respectively. Scale bar: 20 μm. Colocalized PIKfyve and caspase-5 were quantified by ImageJ software (E) (n = 3 independent experiments, n = 18 fields analysed). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "G, H Co-staining of PIKfyve  and Rab5  in WT and SNX10 KO  Caco-2 cells treated with or without OMVs (100 μg/mL) for 24 h (G). Anti-PIKfyve and anti-Rab5 antibodies were used to detect endogenous  PIKfyve and Rab5 respectively. Scale bar: 20 μm. Colocalized PIKfyve and caspase-5 were quantified by ImageJ software (H) (n = 3 independent experiments, n = 18 fields analysed). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001.",
    "ncbi_link": "SNX10: 29887"
  },
  {
    "caption": "I LPS levels in the  cytosolic and residual fractions of Caco-2  cells stimulated by OMVs  (100 μg/mL) with or without apilimod (30 nM) for the indicated time were detected by  LAL assay (n = 6 independent experiments). J  Caco-2 cells transfected with control siRNA or CASP5 siRNA were treated with OMVs (100 μg/mL) for the indicated time.  LPS levels in the cytosolic and residual fractions of Caco-2 cells were detected by  LAL assay (n = 6 independent experiments). K LPS levels in the cytosolic  and residual fractions of Caco-2 cells stimulated by  OMVs  (100μg/mL) with or without bafetinib (1μM) for the indicated time were detected by LAL assay (n = 6 independent experiments). Data information: Data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. ***p < 0.001. ",
    "ncbi_link": "CASP5: 838"
  },
  {
    "caption": "SNX10 conditional knockout (SNX10 cKO) mice  with or without  IL-10 KO background and littermate wild type (WT) mice with or without IL-10  KO background were compared (n = 6 animals, each group). B, C Length of  colons from WT, SNX10 cKO, IL-10 KO and SNX10 cKO IL-10 KO  mice was measured (B) and analysed (C) at the 16th week. Data information: data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "IL-10: 16153
SNX10: 71982"
  },
  {
    "caption": "SNX10 conditional knockout (SNX10 cKO) mice with or without IL-10 KO background and littermate wild type (WT)  mice with or without IL-10 KO background were compared (n = 6 animals, each group). E, F Representative H&E images of colon tissues of WT, SNX10 cKO,  IL-10 KO and SNX10  cKO IL-10  KO mice  at the 16th week were shown (E) and analyzed (F). Scale bar: 100 μm. Data information: data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "IL-10: 16153
SNX10: 71982"
  },
  {
    "caption": "SNX10 conditional knockout (SNX10 cKO)  mice with or without IL-10  KO background and littermate wild type (WT) mice with or without IL-10 KO background were compared (n = 6 animals, each group). G The content of TNF-α,  IL-6, IL-12/IL-23 p40 and IL-17A in the serum of WT, SNX10 cKO, IL-10 KO and SNX10 cKO IL-10 KO mice  at the 16th week were measured by ELISA. Data information: data are means ± SD. One-way ANOVA followed by Bonferroni post hoc test was used for statistical analyzes. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "IL-10: 16153
SNX10: 71982"
  },
  {
    "caption": "SNX10 conditional knockout (SNX10 cKO) mice with or without  IL-10 KO background and littermate wild type (WT) mice with or without IL-10 KO background were compared (n = 6 animals, each group). J Protein expression of  E-cadherin, p-Lyn and Lyn in colon epithelial tissues was determined by immunoblots.",
    "ncbi_link": "IL-10: 16153
SNX10: 71982"
  },
  {
    "caption": "(C) Representative flow cytometry results showing CD71, a cell surface marker, can be efficiently knocked-down in the majority of organoid cells after 5 days of Dox  and TMP  treatment. N = 3 different organoid lines and 3 different gRNAs for CD71  were used. Mean ± SEM is labelled.",
    "ncbi_link": "CD71: 7037"
  },
  {
    "caption": "(B) qRT-PCR  showing that SOX9  gRNAs effectively knocked down SOX9  transcript levels using inducible CRISPRi after 5 days of Dox and TMP  treatment. 3 different organoid lines and 2 different SOX9  gRNAs were used. Error bars: mean ± SEM. Two-sided Student's t-test with equal variance ***p < 0.001.",
    "ncbi_link": "CRISPR: 
SOX9: 6662"
  },
  {
    "caption": "(E) LGR5  mRNA expression  enrichment in SOX9   expressing  tip progenitor cells. SOX9   red, LGR5  cyan. (F) Tip progenitor cells are of high WNT signalling activity. NOTUM   yellow, SOX9   red. Data information: Scale bars = 50 μm",
    "ncbi_link": "LGR5: 8549"
  },
  {
    "caption": "(H) qRT-PCR  showing rescue of SOX9  transcription after constitutively activated β-catenin  overexpression in organoids  cultured without WNT   activators. N = 3 different organoid lines. Error bars: mean ± SEM.",
    "ncbi_link": "β-catenin: 1499
SOX9: 6662"
  },
  {
    "caption": "(I) WB  showing SOX9  protein was rescued after constitutively activated β-catenin overexpression in organoids  cultured without WNT   activators.",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "(A,B) HCR  images showing ETV5  (A) and ETV4  (B) expression  in SOX9  expressing  tip progenitors. ETV4/5 red, SOX9  cyan. Data information: Scale bars denote 50 μm (A, B)",
    "ncbi_link": "ETV4: 2118
ETV5: 2119
SOX9: 6662"
  },
  {
    "caption": "(C) qRT-PCR showing ETV4  and ETV5  dual knockdown in  tip organoids. N =3 different organoid lines and 2 different ETV4  and ETV5  gRNA combinations were used. Error bars: mean ± SEM. Two tailed paired t-test: **p < 0.01; ***p < 0.001.",
    "ncbi_link": "ETV4: 2118
ETV5: 2119"
  },
  {
    "caption": "(F) qRT-PCR of ETV4, ETV5  and SOX9 expression  level in organoids  in self-renewing medium and self-renewing medium without RTK   ligands. N = 3 different organoid lines used. Error bars: mean ± SEM. Two-tailed paired T-test: **p < 0.01; n.s. non-significant.",
    "ncbi_link": "ETV4: 2118
ETV5: 2119
SOX9: 6662"
  },
  {
    "caption": "(B) Lysates from 293T  cells transfected with HA-TRIM21  and Flag-SIRT5  or vector control (-) as indicated were immunoprecipitated  (IP) using anti-Flag  antibody, and bound proteins were analyzed by  western blotting (WB). Data information: All IP  and WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
SIRT5: 23408
TRIM21: 6737"
  },
  {
    "caption": "(F) Immunoblot  (IB) analysis of whole-cell lysates (WCLs) and immunoprecipitates (IPs) derived from 293T cells transfected with Flag-SIRT5  together with HA-TRIM21 or indicated HA-tagged mutant TRIM21  constructs. Cells were treated with 10 μM MG132  for 4 hours before harvesting. HA, hemagglutinin.",
    "ncbi_link": "Flag: 
HA: 
SIRT5: 23408
TRIM21: 6737"
  },
  {
    "caption": "(G) IB  analysis of WCLs derived from 293T  cells transfected with increasing amounts of Flag-TRIM21  construct. Where indicated, 10 μM MG132  was added for 4 hours before harvesting.",
    "ncbi_link": "Flag: 
TRIM21: 6737"
  },
  {
    "caption": "(H) 293T  cells transfected with control or TRIM21  siRNA for 48 hours were then treated with 100 ng/mL CHX  for the indicated time  period before harvesting. Protein expression was analyzed by  western blotting (left panel). The SIRT5  protein abundance was quantified by ImageJ and plotted as indicated (right panel). Data information: All WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "(I) IB  analysis of WCLs derived from TRIM21+/+ and TRIM21-/- BMDMs  treated with 100 ng/ml CHX  for the indicated time  period  before harvesting (left panel). The SIRT5  protein abundance was quantified (right panel).",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "(J) IB  analysis of WCLs derived from TRIM21+/+ and TRIM21-/- BMDMs treated with 100 ng/mL LPS  for the indicated time  period before harvesting (top panel). The SIRT5  protein abundance was quantified (bottom panel).",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "(B) WCLs from TRIM21+/+ and TRIM21-/- BMDMs  treated with 100 ng/mL LPS  for 4 hours were immunoprecipitated  with anti-SIRT5  antibody and analyzed by western blotting. 10 μM MG132  was added for 4 hours before harvesting. Data information: All IP  and WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "(E) WCLs from TRIM21+/+ and TRIM21-/- BMDMs  treated with 100 ng/mL LPS  for 4 hours were immunoprecipitated  with anti-SIRT5  antibody and analyzed by  western blotting using antibodies specifically against Ub-K48 and Ub-K63. 10 μM MG132  was added for 4 hours before harvesting. Data information: All IP  and WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "(A) Lysates from 293T  cells transfected with HA-HAUSP  and Flag-SIRT5  or vector control (-) as indicated were immunoprecipitated  (IP) using anti-Flag  antibody, and bound proteins were analyzed by  western blotting (WB). Data information: All IP  and WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
SIRT5: 23408
HAUSP: 7874"
  },
  {
    "caption": "(E) 293T  cells were transfected with Flag-tagged HAUSP, mutant HAUSP-CS (C223S) or vector control as indicated for 48 hours. protein expression was determined by western blot  analysis using indicated antibodies. Data information: All WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "Flag: 
HAUSP: 7874"
  },
  {
    "caption": "(F) IB  analysis of WCLs derived from 293T  cells transfected with HA-SIRT5  together with Flag-HAUSP  or vector control constructs (left panel). Cells were treated with 100 ng/ml CHX  for the indicated time  period  prior to harvesting. The SIRT5  protein abundance was quantified (right panel).",
    "ncbi_link": "Flag: 
HA: 
SIRT5: 23408
HAUSP: 7874"
  },
  {
    "caption": "(F) IB  analysis of WCLs and anti-SIRT5 immunoprecipitated  products derived from BMDMs  transfected with control or HAUSP  siRNA for 48 hours. 10 μM MG132  was added for 6 hours before harvesting.",
    "ncbi_link": "HAUSP: 252870"
  },
  {
    "caption": "(G) BMDMs  transfected with control (-) or HAUSP  siRNA for 48 hours were then treated with 100 ng/mL mM LPS  for 4 hours, and 10 μM MG132  was added for 4 hours before harvesting. WCLs and anti-SIRT5 immunoprecipitated  products were prepared and subjected to IB  analysis using indicated antibodies.",
    "ncbi_link": "HAUSP: 252870"
  },
  {
    "caption": "(B) IB  analysis of WCLs and anti-TRIM21 immunoprecipitated  products derived from 293T  cells transfected with control or SIRT5  siRNA using anti-Flag, anti-acetyl Lysine (AcK), anti-succinyl Lysine (SulK), anti-glutaryl Lysine (GluK) and anti-malonyl Lysine (MalK) antibodies.",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(E) Protein expression in SIRT5+/+ and SIRT5-/- BMDMs  was determined by  western blot  analysis. Data information: All WB  data in this work otherwise indicated are representative of at least three independent experiments.",
    "ncbi_link": "SIRT5: 68346"
  },
  {
    "caption": "(E) Genotyping of TRIM21-/-, SIRT5-/- and TRIM21-/-SIRT5-/- mice. DNA derived from the tail of wild type and knockout animals was analyzed by PCR. Protein expression of TRIM21  and SIRT5  in BMDMs  derived from mice  were also analyzed by  western blotting. Data information: Western blots in E represent three independent experiments.",
    "ncbi_link": "SIRT5: 68346
TRIM21: 20821"
  },
  {
    "caption": "wild-type (WT, n=5), TRIM21-/- (n=5), SIRT5-/-(n=5), and TRIM21-/-SIRT5-/- (n=5) mice  were orally administrated with 2.5% (w/v) DSS  in drinking water for 7 days and regular drinking water for another 2 days. Colon-length (G) changes were measured. Data information: Data are means ± SD. n=5 biological replicates. P values were determined by unpaired two-tailed Student's t-tests. ns, not significant; ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "SIRT5: 68346
TRIM21: 20821"
  },
  {
    "caption": "(A-D) Immunostaining  with dopamine  antibody at late 3rd instar  (96h AEL) in control background (domeMESO-GFP/+). The inset shows DomeGFP+ cells (B') and the corresponding dopamine  levels (C') in them. (E-L) Similar expression  analysis of dopamine  at early 3rd (72h AEL, E-H) and early 2nd instar (48h AEL, I-L). (D, H and L) The spectral mode of iDopamine  representation with blue pixels indicating low and red pixels indicating high intensity. (M) Quantifications of dopamine  levels in DomeGFP+ progenitors  (domeMESO-Gal4, UAS-GFP/+, n= 14 at 48h, n=13 at 72h and n=16 at 96h AEL). Data information: DNA  is stained  with Hoechst  in blue, intracellular Dopamine  (iDopamine) in red, domeMESO expression  in green (representative of progenitors  in the  medullary zone, MZ). The iDopamine channel has been converted to spectral mode in panels D, H and L. All image panels show a 20µm scale bar. The inset represents a 2X zoom of region of interest (ROIs) marked in white dashed square. AEL indicates After Egg Laying. For better representation, the primary lobe  of the lymph gland  has been represented and outlined in white dashed lines while the MZ  is outlined in yellow dashed line for segregation between Dome+ and Dome- cells. The quantification in M shows median with whiskers indicating the maximum and minimum values,. box indicates the lower and upper quartiles. The statistical analysis applied is One-way ANOVA with Tukey's multiple comparisons test. 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. For better representation, the primary lobe  of the  lymph gland has been represented and outlined in white dashed lines while the MZ  is outlined in yellow dashed line.",
    "ncbi_link": "GFP: 
dome: 32976
Gal4: 855828"
  },
  {
    "caption": "(B-D') A temporal expression  profile of TH  at 48, 72 and 96h AEL lymph glands in control background (domeMESO-Gal4, UAS-GFP/+) (E-G') A temporal expression  profile of Ddc  at 48, 72 and 96h AEL lymph glands in control background (domeMESO-Gal4, UAS-GFP/+). (H) Quantification of TH  levels (domeMESO-Gal4, UAS-GFP/+, n=18 at 48h, n= 15, at 72h and n= 23 at 96h AEL). (I) Quantification of Ddc  levels (domeMESO-Gal4, UAS-GFP/+, n= 17 at 48h, n= 33 at 72h and n= 38 at 96h AEL). Data information: DNA  is stained  with Hoechst  in blue, iDopamine in red, Tyrosine hydroxylase (TH) and Dopa decarboxylase  (Ddc) in red, domeMESO (representative of progenitors) expression  in green, AEL indicates After Egg Laying. The quantifications in H, I represents the median with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in H, I, is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. For better representation, the primary lobe  of the lymph gland has been represented and outlined in white dashed lines while the MZ  is outlined in yellow dashed line.",
    "ncbi_link": "GFP: 
dome: 32976
Gal4: 855828"
  },
  {
    "caption": "(J-L) Assessment of dopamine  levels upon the knockdown of TH  and Ddc  in the progenitors  using domeMESO-Gal4, UAS-GFP. (M) The mean intensity quantification of dopamine  levels upon TH  and Ddc  loss of function in the progenitors  (domeMESO-Gal4, UAS-GFP/+, n=40, domeMESO-Gal4, UAS-GFP; THRNAi, n= 17, domeMESO-Gal4, UAS-GFP; DdcRNAi, n= 34). Data information: DNA  is stained   with Hoechst  in blue, iDopamine in red All image panels show a 20µm scale bar. The quantifications in M represents the median with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in M, is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. For better representation, the primary lobe  of the lymph gland  has been represented and outlined in white dashed lines",
    "ncbi_link": "GFP: 
Ddc: 35190
dome: 32976
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(N-P) The loss of progenitor TH  and Ddc  function using domeMESO-Gal4, UAS-GFP  analysed at wandering 3rd instar, 120h AEL. Data information: DNA  is stained  with Hoechst  in blue, domeMESO  (representative of progenitors) expression  in green, P1 (representative of mature plasmatocytes) in red. All image panels show a 20µm scale bar. AEL indicates After Egg Laying. For better representation, the primary lobe  of the lymph gland has been represented and outlined in white dashed lines",
    "ncbi_link": "GFP: 
Ddc: 35190
dome: 32976
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(Q) Quantifications of  lymph gland  size upon loss of TH  (domeMESO-Gal4, UAS-GFP; THRNAi, n= 34) and Ddc  (domeMESO-Gal4, UAS-GFP; DdcRNAi, n= 56) when compared to stage matched control (domeMESO-Gal4, UAS-GFP/+, n=90). Data information: The quantifications in Q represent mean with standard deviation with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
Ddc: 35190
dome: 32976
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(R) Quantifications of the proportions of %Dome (green bars), %negative (blue bar), %overlap (Dome  and P1, yellow bars) and %P1  (red bars). For Dome  positive area (domeMESO-Gal4, UAS-GFP/+, n=27, domeMESO-Gal4, UAS-GFP; THRNAi, n= 15 and domeMESO-Gal4, UAS-GFP; DdcRNAi, n= 18), negative and overlap areas (domeMESO-Gal4, UAS-GFP; THRNAi, n= 15, domeMESO-Gal4, UAS-GFP; DdcRNAi, n= 18) and P1  positive area (domeMESO-Gal4, UAS-GFP/+, n=27, domeMESO-Gal4, UAS-GFP;  THRNAi, n= 15 and domeMESO-Gal4, UAS-GFP;  DdcRNAi, n= 18). Data information: The quantifications in R represents mean with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in R is Two-way Anova with Tukey's multiple comparisons test. 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
Ddc: 35190
dome: 32976
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(S) Quantification of the number of PPO  positive crystal cells upon dopamine  synthesis perturbation (domeMESO-Gal4, UAS-GFP/+, n=29, domeMESO-Gal4, UAS-GFP; THRNAi, n= 21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n= 23). Data information: The quantifications in S represent mean with standard deviation with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in S is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
Ddc: 35190
dome: 32976
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(A-C') Expression  profile of dopamine activation  based receptor sensor (DA1m) in the progenitors  using domeMESO-Gal4  driver in a temporal  manner- 48h, (A-A'), 72h, (B-B') and 96h AEL, (C-C'). (D) Quantification of the number  DA1m+ cells, %DA1m positive cells (domeMESO-Gal4; DA1m, n=10 at 96h, n=16 at 72h and n=10 at 48h AEL). Data information: DNA is stained  with Hoechst  in blue, lifeAct-RFP to mark progenitors in red, Dopamine  receptor-based reporter (DA1m) in green, All image panels show a 20µm scale bar. AEL indicates After Egg Laying. The quantification in D represents the median with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in is Two-way Anova with Tukey's multiple comparisons test. 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. For better representation, the primary lobe  of the lymph gland  has been represented and outlined in white dashed lines while the MZ  is outlined in yellow dashed line.",
    "ncbi_link": "DA1m: 
dome: 32976
Gal4: 855828"
  },
  {
    "caption": "(I-K) The loss of progenitor Dop2R and DAT  function using domeMESO-Gal4, UAS-GFP  analysed at wandering 3rd instar, 120h AEL. Data information: DNA  is stained  with Hoechst in blue domeMESO (representative of progenitors) expression  in green, P1  (representative of mature plasmatocytes) in red. All image panels show a 20µm scale bar. For better representation, the primary lobe  of the lymph gland has been represented and outlined in white dashed lines",
    "ncbi_link": "GFP: 
DAT: 36849
dome: 32976
Dop2R: 33007
Gal4: 855828"
  },
  {
    "caption": "(L) Quantifications of  lymph gland size upon loss of Dop2R and DAT  in the progenitors  (domeMESO-Gal4, UAS-GFP/+, n= 46, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 44, domeMESO-Gal4, UAS-GFP; DATRNAi, n= 37). Data information: The quantification in L represents mean with standard deviation with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in L is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of lymph gland lobes analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
DAT: 36849
dome: 32976
Dop2R: 33007
Gal4: 855828"
  },
  {
    "caption": "(M) Quantifications of the proportions of %Dome  (green bar), %negative (blue bar), %overlap (Dome  and P1, yellow bar) and %P1  (red bars) upon loss of Dop2R  and DAT  in the progenitors. For Dome  positive area (domeMESO-Gal4, UAS-GFP/+, n= 28, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 16, domeMESO-Gal4, UAS-GFP;  DATRNAi, n= 23), negative area (domeMESO-Gal4, UAS-GFP/+, n= 28, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 16, domeMESO-Gal4, UAS-GFP; DATRNAi, n= 23), overlap area (domeMESO-Gal4, UAS-GFP/+, n= 26, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 16, domeMESO-Gal4, UAS-GFP; DATRNAi, n= 25) and P1  area (domeMESO-Gal4, UAS-GFP/+, n= 27,  domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 16, domeMESO-Gal4, UAS-GFP;  DATRNAi, n= 23). Data information: The quantification in M represents mean, with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in M is Two-way Anova with Tukey's multiple comparisons test. 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
DAT: 36849
dome: 32976
Dop2R: 33007
Gal4: 855828"
  },
  {
    "caption": "(N) Quantification of the number of PPO  positive  crystal cells upon dopamine  sensing perturbation (domeMESO-Gal4, UAS-GFP/+, n= 29, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n= 26, domeMESO-Gal4, UAS-GFP; DATRNAi, n= 25). Data information: The quantification in N represents mean with standard deviation with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in N is One-way ANOVA with Tukey's multiple comparisons test 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
DAT: 36849
dome: 32976
Dop2R: 33007
Gal4: 855828"
  },
  {
    "caption": "(A) A temporal  analysis of total number of nuclei  across development in control background (domeMESO-Gal4, UAS-GFP/+, n= 37 at 48h, n= 31 at 72h, n= 19 at 96h and n= 23 at 120h AEL). The loss of dopamine  modules at 48h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=19,  domeMESO-Gal4, UAS-GFP; DdcRNAi, n=16, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=30 and  domeMESO-Gal4, UAS-GFP; DATRNAi, n=21), at 72h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=22, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=24, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=33 and domeMESO-Gal4, UAS-GFP;  DATRNAi, n=27), at 96h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=18, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=20 and  domeMESO-Gal4, UAS-GFP; DATRNAi, n=22) and at 120h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=25, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=30, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=25 and domeMESO-Gal4, UAS-GFP; DATRNAi, n=31). Data information: The quantification represents median with whiskers representing maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis is Two-way Anova with Tukey's multiple comparisons test while the control comparison, domeMESO-Gal4, UAS-GFP/+, for different  time points was done by One-way ANOVA with Tukey's multiple comparisons test. 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. AEL indicates After Egg Laying",
    "ncbi_link": "GFP: 
DAT: 36849
Ddc: 35190
dome: 32976
Dop2R: 33007
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(B) Quantification of total Dome+ nuclei  counts of control animals (domeMESO-Gal4, UAS-GFP/+, n= 37 at 48h, n= 28 at 72h, n= 19 at 96h and n=23 at 120h AEL). The loss of dopamine  modules at 48h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=22, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=16, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=30, domeMESO-Gal4, UAS-GFP; DATRNAi, n=21), at 72h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=22, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=24, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=32, domeMESO-Gal4, UAS-GFP; DATRNAi, n=27), at 96h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=17, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=20, domeMESO-Gal4, UAS-GFP; DATRNAi, n=22) and at 120h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=24, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=30, domeMESO-Gal4, UAS-GFP;  Dop2RRNAi, n=25, domeMESO-Gal4, UAS-GFP;  DATRNAi, n=30). (C) A temporal analysis of Dome- nuclei  counts in the control animals (domeMESO-Gal4, UAS-GFP/+, n= 37 at 48h, n= 28 at 72h, n= 18 at 96h, n= 23, at 120h AEL). The perturbation of the dopamine  modules in the progenitors  at 48h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=22,  domeMESO-Gal4, UAS-GFP; DdcRNAi, n=16, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=30, domeMESO-Gal4, UAS-GFP; DATRNAi, n=21), at 72h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=22, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=24, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=32,  domeMESO-Gal4, UAS-GFP; DATRNAi, n=27), at 96h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP;  DdcRNAi, n=17, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=20, domeMESO-Gal4, UAS-GFP; DATRNAi, n=22) and at 120h AEL (domeMESO-Gal4, UAS-GFP; THRNAi, n=24, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=30, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=25, domeMESO-Gal4, UAS-GFP; DATRNAi, n=30). Data information: The quantification represents median with whiskers representing maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied is Two-way Anova with Tukey's multiple comparisons test while the control comparison,  domeMESO-Gal4, UAS-GFP/+, for different  time points was done by One-way ANOVA with Tukey's multiple comparisons test. 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. AEL indicates After Egg Laying",
    "ncbi_link": "GFP: 
DAT: 36849
Ddc: 35190
dome: 32976
Dop2R: 33007
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(A) Quantification of the Dome+ BrdU  index normalised to Dome+ nuclei  in a time course manner with dopamine modules perturbed in the progenitors  using domeMESO-Gal4, UAS-GFP  driver. At 48h AEL (domeMESO-Gal4, UAS-GFP/+, n=11, domeMESO-Gal4, UAS-GFP; THRNAi, n=13, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=11, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=15, domeMESO-Gal4, UAS-GFP;  DATRNAi, n=5), at 72h AEL (domeMESO-Gal4, UAS-GFP/+, n=34,  domeMESO-Gal4, UAS-GFP; THRNAi, n=31, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=16, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=15, domeMESO-Gal4, UAS-GFP; DATRNAi, n=27) and at 96h AEL (domeMESO-Gal4, UAS-GFP/+, n=17, domeMESO-Gal4, UAS-GFP; THRNAi, n=28, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=20,  domeMESO-Gal4, UAS-GFP;  Dop2RRNAi, n=17, domeMESO-Gal4, UAS-GFP; DATRNAi, n=22). (B) Quantification of the Dome+ mitotic index  normalised to Dome+ nuclei  in a  time course manner with loss of dopamine  modules in the progenitors using domeMESO-Gal4, UAS-GFP  driver. At 48h AEL (domeMESO-Gal4, UAS-GFP/+, n=35, domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=16, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=30, domeMESO-Gal4, UAS-GFP; DATRNAi, n=20), at 72h AEL (domeMESO-Gal4, UAS-GFP/+, n=27, domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=23, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=31, domeMESO-Gal4, UAS-GFP; DATRNAi, n=27) and at 96h AEL (domeMESO-Gal4, UAS-GFP/+, n=19, domeMESO-Gal4, UAS-GFP; THRNAi, n=21, domeMESO-Gal4, UAS-GFP; DdcRNAi, n=17, domeMESO-Gal4, UAS-GFP; Dop2RRNAi, n=20, domeMESO-Gal4, UAS-GFP; DATRNAi, n=22). Data information: AEL indicates After Egg Laying. The quantifications in A and B represent median with whiskers indicating maximum and minimum value, box indicates the lower and upper quartiles The statistical analysis applied is Two-way Anova with Tukey's multiple comparisons test. 'n' represents the number of  lymph gland lobes   analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
DAT: 36849
Ddc: 35190
dome: 32976
Dop2R: 33007
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(C) Quantifications of %G1, %S and %G2/M at different time points, in control and dopamine  perturbed backgrounds, color coding scheme to represent the  cell cycle phase as shown through FUCCI  reporter is below the graph. Across development, at 48h AEL (domeMESO-Gal4; UAS-FUCCI/+, n=34, domeMESO-Gal4; UAS-FUCCI; THRNAi, n= 13, domeMESO-Gal4; UAS-FUCCI;  DdcRNAi, n= 15,  domeMESO-Gal4; UAS-FUCCI; Dop2RRNAi, n= 19, domeMESO-Gal4; UAS-FUCCI; DATRNAi, n= 17), at 72h AEL (domeMESO-Gal4; UAS-FUCCI/+, n=38, domeMESO-Gal4; UAS-FUCCI; THRNAi, n= 22, domeMESO-Gal4; UAS-FUCCI; DdcRNAi, n= 29, domeMESO-Gal4; UAS-FUCCI; Dop2RRNAi, n= 47, domeMESO-Gal4; UAS-FUCCI; DATRNAi, n= 29) and at 96h AEL (domeMESO-Gal4; UAS-FUCCI/+, n=55, domeMESO-Gal4; UAS-FUCCI; THRNAi, n= 14, domeMESO-Gal4; UAS-FUCCI; DdcRNAi, n= 19, domeMESO-Gal4; UAS-FUCCI; Dop2RRNAi, domeMESO-Gal4; UAS-FUCCI; DATRNAi, n= 19) Data information: FUCCI (fluorescent ubiquitination-based cell cycle indicator) reporter shows G1 phase cells in green, S phase  cells in red and G2/M phase cells in yellow. AEL indicates After Egg Laying. The quantifications in in C represents mean. The statistical analysis applied is Two-way Anova with Tukey's multiple comparisons test. The domeMESO-Gal4; UAS-FUCCI  control comparison temporally in C is analysed using One-way ANOVA with Tukey's multiple comparisons test. 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "FUCCI: 
DAT: 36849
Ddc: 35190
dome: 32976
Dop2R: 33007
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(A-I'') Representative  lymph gland images at 48, 72 and 96h AEL depicting the  lymph gland growth trajectory along with dopamine  level status in the PSC  and remaining  lymph gland. (A-C'') The control profile of lymph gland and PSC  iDopamine levels at 48h (A-A''), 72h (B-B'') and 96h (C-C''). (D-I'') Downregulation of the dopamine  synthesising enzymes TH  and Ddc  in the PSC  at 48h (D-D'' and G-G''), 72h AEL (E-E'' and H-H'') and at 96h AEL (F-F'' and I-I''). (J) Quantification of mean dopamine  intensity in the PSC  at upon PSC  perturbation of dopamine  synthesis at 48h AEL (Antp-Gal4; UAS-GFP/+, n=33, Antp-Gal4; UAS-GFP; THRNAi, n=8, Antp-Gal4; UAS-GFP; DdcRNAi, n=14), at 72h AEL (Antp-Gal4; UAS-GFP/+, n=26, Antp-Gal4; UAS-GFP; THRNAi, n=25, Antp-Gal4; UAS-GFP;  DdcRNAi, n=20) and 96h AEL (Antp-Gal4; UAS-GFP/+, n=15, Antp-Gal4; UAS-GFP; THRNAi, n=13, Antp-Gal4; UAS-GFP; DdcRNAi, n=17). (K) Quantification of mean dopamine  levels in the  lymph gland upon PSC  perturbation of dopamine  synthesis at 48h AEL (Antp-Gal4; UAS-GFP/+, n=28, Antp-Gal4; UAS-GFP; THRNAi, n=13, Antp-Gal4; UAS-GFP; DdcRNAi, n=18), at 72h AEL (Antp-Gal4; UAS-GFP/+, n=25, Antp-Gal4; UAS-GFP;  THRNAi, n=24, Antp-Gal4; UAS-GFP;  DdcRNAi, n=22) and 96h AEL (Antp-Gal4; UAS-GFP/+, n=15, Antp-Gal4; UAS-GFP; THRNAi, n=16, Antp-Gal4; UAS-GFP; DdcRNAi, n=18). Data information: DNA is stained  with Hoechst  in blue, Antp-Gal4; UAS-GFP  (representative of Posterior Signaling Center, PSC) in green, iDopamine in red. All image panels show a 20µm scale bar. AEL indicates After Egg Laying. The quantification in J, K represents the median with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in J, K is Two-way Anova with Tukey's multiple comparisons test. The control animals Antp-Gal4; UAS-GFP/+ were analysed by One-way Anova with Tukey's multiple comparisons test across time points. 'n' represents the number of  lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. For better representation, the primary lobe  of the  lymph gland  has been represented and outlined in white dashed lines and the PSC in yellow dashed line.",
    "ncbi_link": "GFP: 
Antp: 40835
Ddc: 35190
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "(L) Analysis of the total cell counts upon loss of TH  and Ddc  in the PSC  at 48h AEL (Antp-Gal4; UAS-GFP/+, n=19, Antp-Gal4; UAS-GFP; THRNAi, n=13, Antp-Gal4; UAS-GFP; DdcRNAi, n=17), at 72h AEL (Antp-Gal4; UAS-GFP/+, n=17, Antp-Gal4; UAS-GFP; THRNAi, n=18, Antp-Gal4; UAS-GFP; DdcRNAi, n=22) and 96h AEL (Antp-Gal4; UAS-GFP/+, n=15, Antp-Gal4; UAS-GFP; THRNAi, n=14, Antp-Gal4; UAS-GFP; DdcRNAi, n=15) Data information: The quantification in L represents the median with whiskers indicating maximum and minimum values, box indicates the lower and upper quartiles. The statistical analysis applied in L is Two-way Anova with Tukey's multiple comparisons test. 'n' represents the number of lymph gland lobes  analyzed, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: 
Antp: 40835
Ddc: 35190
Gal4: 855828
TH: 38746"
  },
  {
    "caption": "A. Western blot analysis of Tace using lysates from WT and TaceFl/Fl;P0-Cre mousesciatic nerves at P10 (65ug of total protein lysate loaded). The arrowhead indicates the pro-protein and the arrow shows the cleaved active form of Tace. Representative of two independent experiments.",
    "ncbi_link": "Cre: 
Tace: 11491
P0: 17528"
  },
  {
    "caption": "C. Western blot analysis of Tace in Mtmr2-/- sciatic nerves at P5, P10, and P20. Representative of two independent experiments.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "D. Western blot analysis of Tace using lysates from Mtmr2-/- mouse sciatic nerves at 5 months, with quantification, p=0.10, two-tailed Mann Whitney U test. Representative of two independent experiments.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "E. Phosphorylation of ErbB2 in Mtmr2-/- sciatic nerves at P2, P10 and P15. At P2, each lane is a pool of n=7 animals per genotype, representative of six independent experiments using n=6 different nerve pools per genotype, and quantification using WT values arbitrary set to1, p=0.0313, Wilcoxon Rank Sum test. At P10 and P15, mean values of two samples are shown. At P10, each lane is a pool of n=3/4 animals per genotype, representative of three independent experiments using n=6 different pools per genotype. Nf-l is the neurofilament light chain and Clx is calnexin.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "F. Phosphorylation of ErbB2 in Mtmr2-/- Schwann cell/DRG neuron co-cultures after 4 days of ascorbic acid treatment. Each lane is a pool from at least 10 coverslips/DRG per genotype. Representative of two independent experiments using n=4 different pools of coverslips/DRG per genotype, p=0.20, two-tailed Mann Whitney U test.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "A. ShRNA targeting Nrg1 type III were validated in rat purified neurons. Western blot analysis for Nrg1 shows reduction of its expression (pro-protein at 150 KDa) using two different harpins, representative of two independent experiments. Clx is calnexin.",
    "ncbi_link": "Nrg1: 112400"
  },
  {
    "caption": "B. ShRNA#1 and 2 downregulate Nrg1 type III expression also in myelin-forming Schwann cell/DRG neuron co-cultures analyzed after 7 days of ascorbic acid treatment, as shown by western blot analysis, representative of two independent experiments. Clx is calnexin.",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "E. Representative confocal images of Mtmr2-/- co-cultures transduced using LV expressing Nrg1 type III shRNA #1, with quantification of the percentage of myelin outfoldings, n= number of DRG/coverslips, n= 9, 382 fibers (SCR), n=9, 368 fibers (LV #sh1, 12.5%), n= 8, 327 fibers (LV #sh1, 25%). Asterisks indicate fibers with myelin outfoldings. Results are mean ± SEM, p<0.0001, nonparametric one-way ANOVA, followed by Dunn's post hoc test, representative of two independent experiments.",
    "ncbi_link": "Mtmr2: 77116
Nrg1: 211323"
  },
  {
    "caption": "E. Western blot analysis of Nrg1 and Akt phosphorylation (S473) shows that activation of Akt decreases following Nrg1 type III downregulation (p-Akt/Akt/Actin, ratio between Mtmr2-/- Scramble-treated and Mtmr2-/- sh#1-treated using 12.5% LV is 1 : 0.85). Each lane is a pool of at least 10 different DRG/coverslips, representative of two independent experiments. Bar in (C, D) is 100 μm; in (E) is 20 μm.",
    "ncbi_link": "Mtmr2: 77116
Nrg1: 211323"
  },
  {
    "caption": "B. Immunohistochemistry and confocal microscopy of Mtmr2-/- cultures treated with 5ng/ml and 10ng/ml rhTACE, with quantification of the percentage of myelin outfoldings; n=10 (NT), n=10 (5ng/ml), n=11 (10ng/ml), DRGs/coverslips. A total of 547, 557, and 571 Mbp fibers were quantified, respectively, p<0.0001, nonparametric one-way ANOVA, followed by Dunn's post hoc test.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "B. Western blot analysis of lysates from Mtmr2-/- cultures treated using 10ng/ml rhTACE showing Nrg1 expression and Akt activation (S473 phosphorylation). Each lane is a lysate of at least n=10 DRGs/coverslips. In Mtmr2-/- (10ng/ml rhTACE) as compared to Mtmr2-/- (NT), Nrg1(150 KDa)/actin ratio is 0.8:1; Nrg1(65 KDa)/actin ratio is 0.48:1; and p-Akt/Akt/actin ratio is 0.6:1.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "D. Immunohistochemistry and confocal microscopy of Mtmr2-/- cultures treated with 1 mM and 5mM Niacin, with quantification of the percentage of myelin outfoldings; n=31 (NT), n=14 (1mM), and n=29 (5mM) DRGs/coverslips from two independent experiments. A total of 1256, 489, and 1305 fibers, respectively, were quantified, p<0.0001, nonparametric one-way ANOVA, followed by Dunn's post hoc test.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "D. Tace activity was measured from lysates of Niacin-treated cultures, n=7 (KO NT) and n=8 (KO 5mM Niacin) number of independent plates, each containing from 10-15 DRGs plated. Note that Tace activity was similar between WT and Mtmr2-/- cultures, one-tailed Mann Whitney U test, p=0.037.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "E. Niacin treatment of Tace-/- explants does not rescue hypermyelination, with quantification, n=8 DRGs/coverslips per condition, p=0.0056, nonparametric one-way ANOVA, followed by Dunn's post hoc test. Representative of three independent experiments.",
    "ncbi_link": "Tace: 11491"
  },
  {
    "caption": "A. Representative images of semithin section analysis of sciatic nerves from Mtmr2-/- and Mtmr2-/-;Nrg1 (III)+/- mice at 6 months. Myelin outfoldings (arrowheads) are reduced in Mtmr2-/-;Nrg1 (III)+/- nerves (n=9) as compared to Mtmr2-/- (n=8), results are mean ± SEM, p=0.0037, two-tailed Mann Whitney U test.B. G-ratio analysis on sciatic nerves from Mtmr2-/-, Mtmr2-/-;Nrg1 (III)+/-, and Nrg1 (III)+/- mice at 6 months indicates that myelin thickness of Mtmr2-/-;Nrg1 (III)+/- is similar to Nrg1 (III)+/- nerves and different from Mtmr2-/-, which is in the normal range as already reported (Bonneick et al, 2005), n=5 animals per genotype.Mean g-ratios: Mtmr2-/- 0.67 ± 0.03, 2129 fibers, n=5 animals; Mtmr2-/-;Nrg1 (III)+/- 0.71 ± 0.03, 2139 fibers, n=5 animals; Nrg1 (III)+/- 0.72 ± 0.03, 2152 fibers, n=4 animals. Mtmr2-/- as compared to Mtmr2-/-;Nrg1 (III)+/-, p=0.0145; Mtmr2-/- as compared to Nrg1 (III)+/-, p=0.0030, and Mtmr2-/-;Nrg1 (III)+/- as compared to Nrg1 (III)+/- p=0.3193, repeated measures ANOVA.",
    "ncbi_link": "Mtmr2: 77116
Nrg1: 211323"
  },
  {
    "caption": "C. Western blot analysis on lysates from Mtmr2-/-, Mtmr2-/-;Nrg1 (III)+/-, and Nrg1 (III)+/- sciatic nerves at P10 indicates that Akt activation (S473 phosphorylation) is similar between Mtmr2-/-;Nrg1 (III)+/- and Nrg1 (III)+/- consistent with g-ratio findings, representative of three independent experiments. Phosphorylation of Akt is relative to total Akt normalized on calnexin, Clx.",
    "ncbi_link": "Mtmr2: 77116
Nrg1: 211323"
  },
  {
    "caption": "A. Niacin treatment of Vim-/- explants rescues hypermyelination, n=10 DRGs/ coverslips per condition, with quantification, representative of three independent experiments, p=0.0048, nonparametric one-way ANOVA, followed by Dunn's post hoc test.",
    "ncbi_link": "Vim: 22352"
  },
  {
    "caption": "A. Western blot analysis on lysates from treated and not treated explants (at least 10 DRGs/ coverslips per lane) shows that increased Akt activation (S473 phosphorylation) in Vim-/- explants is restored to normal levels following 5 mM Niacin treatment.",
    "ncbi_link": "Vim: 22352"
  },
  {
    "caption": "B. Niaspan treatment of Vim-/- mice does not affect mouse growth, as the growth rate in WT (n=8, saline; n=6 Niaspan) and Vim-/- (n=10 saline and n=10 Niaspan) mice either saline or Niaspan-treated is not significantly different, Linear Mixed Effect (LME) models.",
    "ncbi_link": "Vim: 22352"
  },
  {
    "caption": "B. Niaspan administration (daily i.p. injection of 160mg/Kg Niaspan starting at P15 for 15 days) enhances Tace activity in Vim-/- nerves at P30, n=6 animals per genotype, p=0.0325, one-tailed Mann Whitney U test.",
    "ncbi_link": "Vim: 22352"
  },
  {
    "caption": "C. Semithin section and g-ratio analyses of sciatic nerves at P30 shows that Niaspan does not alter myelin thickness in WT nerves, whereas restores myelin thickness to normal values in Vim-/- nerves. G-ratio values: WT saline, 0.71 ± 0.003, 1872 fibers, n= 5 animals; WT Niaspan, 0.71 ± 0.004, 1882 fibers, n= 5 animals; Vim-/- saline 0.69 ± 0.004, 2313 fibers, n= 6 animals; Vim-/- Niaspan 0.72 ± 0.01, 1616 fibers, n=5 animals. WT saline as compared to Vim-/- saline, p=0.0588; Vim-/- saline as compared to Vim-/- Niaspan, p=0.0431, repeated measures ANOVA, representative of two independent experiments. The number of myelinated fibers is similar between the 4 groups as shown, p=0.3042, nonparametric one-way ANOVA, followed by Dunn's post hoc test.",
    "ncbi_link": "Vim: 22352"
  },
  {
    "caption": "A. Niaspan administration (daily i.p. injection of 160mg/Kg starting at P15 for 60 days) does not affect the growth of Mtmr2-/- mice. The growth rates of Mtmr2-/- and WT both saline-treated are significantly different, p<0.0001, Linear Mixed Effect (LME) models, as already reported (Bolino et al, 2004), n=8 animals per condition.",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "B. Niaspan administration reduces the percentage of myelin outfoldings (red asterisks) in Mtmr2-/- sciatic nerves without affecting the number of myelinated fibers as assessed by semithin section analysis at P75, n= 8 mice per genotype, results are mean ± SEM, p=0.0093, two-tailed Mann Whitney U test, representative of three independent experiments. Niaspan treatment does not alter myelin thickness in WT or Mtmr2-/- mice as assessed by g-ratio analysis (WT saline-treated, 0.67 ± 0.003, 2014 fibers; Mtmr2-/- Niaspan-treated, 0.67 ± 0.007, 1924 fibers; Mtmr2-/- saline-treated, 0.68 ± 0.003, 2244 fibers; n=4 animals per condition).",
    "ncbi_link": "Mtmr2: 77116"
  },
  {
    "caption": "A. Western blot analysis of lysates from Pmp22+/- and WT sciatic nerves at P10 shows that Akt phosphorylation (S473) is increased in Pmp22+/- nerves, results are mean ± SEM, p=0.0317, two-tailed Mann Whitney U test, representative of two independent experiments.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "B. Western blot analysis of Tace using lysates from Pmp22+/- and WT sciatic nerves at different stages of development. The arrowhead indicates the pro-protein and the arrow shows the cleaved active form of Tace. Representative of two independent experiments.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "B. Tace activity as measured in Pmp22+/- and WT sciatic nerves at P30 (n=6 mice per genotype, results are mean ± SEM, p=0.0070, two-tailed Mann Whitney U test).",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "C. Representative images of semithin section analysis of sciatic nerves at P45 from Pmp22+/- saline and Pmp22+/- Niaspan-treated mice. Niaspan was administered daily by i.p. injection at 160mg/Kg starting at P15 for 30 days.C'. The percentage of tomacula in sciatic nerves was assessed by ultrastructural analysis, results are mean ± SEM, n= 6 animals per condition, p=0.0022, two-tailed Mann Whitney U test, representative of two independent experiments.D. G-ratio analysis on semithin sections of sciatic nerves shows that increased myelin thickness in Pmp22+/- sciatic nerves at P45 is restored to normal values following Niaspan treatment. Mean g-ratio values, WT saline-treated: 0.69 ± 0.002, 2052 fibers, n=5 animals; Pmp22+/- saline-treated: 0.66 ± 0.003, 2643 fibers, n=6 animals; Pmp22+/- Niaspan-treated, 0.68 ± 0.002, 2311 fibers, n=6 animals. WT saline as compared to Pmp22+/- saline-treated, p<0.0001; Pmp22+/- saline-treated as compared to Pmp22+/- Niaspan-treated, p=0.0002; Pmp22+/- Niaspan-treated as compared to WT saline, p=0.0899; repeated measures ANOVA.E. The number of myelinated fibers is similar between the 3 groups analyzed, p=0.4362, nonparametric one-way ANOVA, followed by Dunn's post hoc test.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "A. Western blot analysis to detect phosphorylation levels of Akt (S473) on lysates from Pmp22-/- and WT mice at P20, with quantification. Results are mean ± SEM, p=0.6857, two-tailed Mann Whitney U test, representative of three independent experiments.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "B. Western blot analysis for Mbp and P0 on lysates from Pmp22-/- and WT mice P20 shows decreased myelin protein expression levels at both time points in Pmp22-/- nerves, results are mean ± SEM, p=0.0500 with the exception of the P0 protein level at P20, for which the difference between Pmp22-/- and WT nerves is not statistically significant, p=0.1000, one-tailed Mann Whitney U test, representative of two independent experiments.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "C. Representative images of semithin section analysis of WT and Pmp22-/- sciatic nerves at P30. Tomacula are abundant in Pmp22-/- nerves at this age, where both fibers with thicker myelin (in the range of <3-4 μm in diameter) and thinner myelin (with diameters greater than 4 μm, particularly in motor fasicles) can be observed.C'. Niaspan does not ameliorate the phenotype in Pmp22-/- mice, as indicated by the number of tomacula (quantification of the percentage of tomacula in the entire sciatic nerve section, results are mean ± SEM, p=0.7400, Mann Whitney U test, n= 15 animals per condition).",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "D. Growth curve of Pmp22-/- mice treated with Niaspan administered by i.p. injection daily at 160mg/Kg and starting at P15 for 15 days. A significant time by group effect is noted between WT saline and Pmp22-/- saline (group effect p=0.9907 and time effect p=0.0057), indicating that the two groups start with similar weight values but then the WT saline group (n=6 animals) grows more in time. When Pmp22-/- saline (n=5) and Pmp22-/- Niaspan-treated (n=6) are compared, the group effect is statistically significant (p=0.0076) while the time effect is not (p=0.6677), suggesting that these two groups have a similar growth trend but Pmp22-/- Niaspan-treated group starts with a higher baseline weight.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "E. Niaspan does not ameliorate myelin thickness as indicated by g-ratio analysis, with axonal diameter distribution: WT 0.68 ± 0.003, 2945 fibers, n=5 animals; Pmp22-/- 0.64 ± 0.003, 1557 fibers, n= 6 animals; Pmp22-/- Niaspan 0.63 ± 0.003, 1445 fibers, n=6 animals, results are mean ± SEM. WT saline as compared to Pmp22-/- saline-treated p<0.0001; WT saline as compared to Pmp22-/- Niaspan-treated p<0.0001, repeated measures ANOVA. Note the loss of myelinated fibers in Pmp22-/- nerves for all caliber axons.",
    "ncbi_link": "Pmp22: 18858"
  },
  {
    "caption": "(A) RPE1 cells were transfected with either scramble or TMEM135 siRNAs and immunostained for LAMP1 as a lysosome marker (red) and PMP70 as a peroxisome marker (green). Scale bar, 10 μm. (B) Quantification of overlap signal between lysosomes and peroxisomes shown in (A). Data represent mean ± SD (n=3 experiments), 50 cells were scored per condition per experiment. *P < 0.05, Student's t-test. ",
    "ncbi_link": "TMEM135: 65084"
  },
  {
    "caption": "(E) Cells transfected with TMEM135 siRNA were subjected to a SREBP2 cleavage assay for the precursor of SREBP2 and nuclear SREBP2.",
    "ncbi_link": "TMEM135: 65084"
  },
  {
    "caption": "(F) Cells transfected with TMEM135 siRNA were subjected to qPCR. Data represent mean ± SD (n=3 experiments), *P < 0.05, Student's t-test.",
    "ncbi_link": "TMEM135: 65084"
  },
  {
    "caption": "(A) RPE1 cells were transfected with siRNAs as indicated, followed by transfection with wild-type pGFP-Rab8a (WT-Rab8), constitutively active pGFP-Rab8a (Q67L) (CA-Rab8), or DN Rab8 dominant-negative pGFP Rab8a (T22N), incubated in serum-starved media for 12 h, and immunostained for ARL13B (Red), GFP-Rab8 (green), and DAPI (blue). Scale bar, 10 μm.",
    "ncbi_link": "pGFP: 
Rab8: 4218
Rab8a: 4218"
  },
  {
    "caption": "(B) Efficiency of IFT20 knockdown by western blot.",
    "ncbi_link": "IFT20: 90410"
  },
  {
    "caption": "(E) Cells were transfected with siRNAs as indicated, followed by transfection with Flag-IFT20, incubation in serum-starvation media for 12 h, and immunostained for ARL13B. Representative fluorescent images of Flag-IFT20 (green), ARL13B (red), and DAPI (blue) are shown. Scale bar, 10 μm. (F) Quantification of the percentage of ciliated cells with both the Flag-IFT20 and ARL13B localized in the cilium. Data represent mean ± SD (n=3 experiments), 150 Flag positive cells were scored per condition per experiment, *P < 0.05, Student's t-test. ",
    "ncbi_link": "Flag: 
IFT20: 55978"
  },
  {
    "caption": "(G) Cells were transfected with siRNAs as indicated, followed by further transfection with CA-Rab8, incubation in serum-starvation media for 12 h, and immunostained for acetylated-tubulin. Representative fluorescent images of GFP-Rab8 Q67L (green), acetylated-tubulin (red), and DNA (blue) are shown. Scale bar, 10 μm. (H) Quantification of the percentage of GFP -positive ciliated cells (only those cilia having both GFP-Rab8 and acetylated-tubulin on cilium were considered for quantification). Data represent mean ± SD (n = 3 experiments), 200 GFP positive cells were scored per condition per experiment, *P < 0.05, Student's t-test.",
    "ncbi_link": "Rab8: 4218"
  },
  {
    "caption": "(A) Efficiency of Rab8a depletion confirmed by Western blot in RPE1 cells.",
    "ncbi_link": "Rab8a: 4218"
  },
  {
    "caption": "(H, I, J) Cells were transfected by siRNAs as indicated, followed by transfection with GFP-Rab8 WT, GFP-Rab8 Q67L, or GFP-Rab8 T22N, and further incubated in serum-starvation media for 12 h. Cell lysate was subjected to immunoprecipitation with anti-GFP antibody, followed by Western blot with antibody against GFP.",
    "ncbi_link": "GFP: 
Rab8: 4218"
  },
  {
    "caption": "mRNA levels of TMX1 (A) and NFAT1 (B) in primary melanocytes, keratinocytes and melanoma cell lines. data are are normalized to the expression of TBP and are presented as mean ± SEM (n≥3).",
    "ncbi_link": "TBP: 
NFAT1: 4773
TMX1: 81542"
  },
  {
    "caption": "Reduced nuclear translocation of NFAT1-GFP in TMX1 or TMX3 silenced (siRNA) melanoma cells. (C) Images show NFAT1-GFP fluorescence intensity before and after stimulation with thapsigargin (Tg; 1 µM) in WM3734 cells. (D) Corresponding time-dependent nuclear import of NFAT1 as a change of F/F0. (E) Normalized endpoint quantification. Same analysis was performed with Mel Juso cells with (F) images, (G) time-dependent nuclear import and (H) normalized endpoint quantification. data are presented as mean ± SEM (n values: WM3734, control=142, TMX1 kd=116, TMX3 kd=148; Mel Juso, control=75, TMX1 kd=47, TMX3 kd=67).",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Thapsigargin (Tg) induced Fura-2 based cytosolic Ca2+ imaging in Ringer's buffer containing 0.25 mM Ca2+. (B) Quantification of basal cytosolic calcium levels and (C) SOCE quantification (plateau-basal) for WM3734 after stable silencing of TMX1 (two clones). : In (B-C), data are presented as mean ± SEM (n values: WM3734, control=939, TMX1 kds 1=988, TMX1 kds 2=508).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Cytosolic Ca2+ imaging (Fura-2) and (E) SOCE quantification (plateau-basal) for WM3734 after transient silencing of TMX1 or TMX3. In (E), data are presented as mean ± SEM (n values: WM3734, control=30, TMX1 kd=49, TMX3 kd=52).",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Cellular H2O2 (HyPer) was evaluated in two melanoma cell lines upon TMX1 kd and TMX3 kd. (F) Exemplary ratiometric images (F505 nm / F420 nm) are shown for WM3734 and Mel Juso. Quantification of basal cellular H2O2 in WM3734 (G) and Mel Juso (H) cells. In (G-H), data are presented as mean ± SEM (n values: WM3734: control=168, TMX1 kd=209, TMX3 kd=192; Mel Juso: control=297, TMX1 kd=343, TMX3 kd=440). In (F) scale bars: 10 µm; color code: WM3734: color code: blue=0, red=3; Mel Juso: color code: blue=0, red=1.5.",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Tg-induced NFAT1-GFP nuclear import in transient TMX1 silenced WM3734 cells and after pre-incubation with 100 µM N-acetylcysteine (NAC) for 48 h.",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Endpoint quantification of the data from (C) and upon treatment with NAC, PEG-catalase (50 U/mL), or DTT (1 mM). data are presented as mean ± SEM (n values: control=73, control+NAC= 19, TMX1 kd=57, TMX1 kd+NAC=63, TMX1 kd+catalase=58, TMX1 kd+DTT=22).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Cytosolic calcineurin activity (CaNAR2) in WM3734 cells with transient knockdown of TMX1 or TMX3 measured upon Tg stimulation.",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Quantification of the basal calcineurin activity and the maximal calcineurin activity (plateau-basal). data are presented as mean ± SEM (n values: control=49, TMX1 kd=48, TMX3 kd=63).",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Quantification of the basal calcineurin activity and the maximal calcineurin activity (plateau-basal) 8 h after treatment with the antioxidant NAC (100 µM) in WM3734 with transient knockdown of TMX1. data are presented as mean ± SEM (n values: control=15, TMX1 kd=24, TMX1 kd+NAC=19).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Mitochondrial H2O2 (mito-HyPer) was measured in two cell lines upon transient TMX knockdown. Exemplary ratiometric images (F505 nm / F420 nm) are shown (A); corresponding quantification for (B) WM3734 and (C) Mel Juso. , data are presented as mean ± SEM (n values: WM3734: control=546, TMX1 kd=510, TMX3 kd=621; Mel Juso: control=416, TMX1 kd=418, TMX3 kd=442).",
    "ncbi_link": "TMX: 81542
TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Mitochondrial Ca2+ uptake in WM3734 with stable TMX1 knockdown was measured using a mitochondria-targeted calcium sensor (4mt-D3cpV) (D). Cells were exposed to 0.25 mM Ca2+ containing Ringer's buffer and Tg. (E) Quantification of basal mitochondrial Ca2+ levels and (F) mitochondrial Ca2+ uptake (basal-plateau). , data are presented as mean ± SEM (n values: control=62, TMX1 kds=45).",
    "ncbi_link": "4mt-D3cpV: 
TMX1: 81542"
  },
  {
    "caption": "Mitochondrial volume was determined using MitoTracker DeepRed in WM3734 cells with stable knockdown of TMX1. The mean mitochondrial volume was modeled based on microscopy, the quantification of mean volume (µm3) and mean surface (µm2) is depicted in (G) and (H) respectively. data are presented as boxplots (n values: control=101, TMX1 kds=90; center line: median; box: 25 % and 75 % percentile; whiskers: 1.5 times interquartile range; outliers are shown as dots).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Peripheral mitochondria were quantified in WM3734 cells with stable knockdown of TMX1. A peripheral mask was applied based on the membrane staining (CellMask Green) and mitochondria covered area (MitoTracker DeepRed) was evaluated (see Fig. 9). Representative images (I) and quantification (J). In (J), data are presented as mean ± SEM (n values: control=163, TMX1 kds=116).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Representative electron micrographs of control and 1205Lu cells with stable TMX1 knockdown (K). Corresponding quantification of the distance between (L) mitochondria and plasma membrane, (M) mitochondria and ER, and (N) the length of the MAM (mitochondria-ER contact site). In (L), data are presented as mean ± SEM (n values: control=100, TMX1 kds= 100). In (M-N), data are presented as mean ± SEM (n values: control=60, TMX1 kds= 60).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Cellular H2O2 concentration (HyPer) 48 h after transient silencing of TMX1 and / or NOX4 in WM3734 cells or after inhibiting NOX4 with GKT137831 (140 nM) (O) Representative ratiometric images (F505 nm / F420 nm) and (P) quantification. In (P), data are presented as mean ± SEM (n values: control=837, TMX1 kd=888, TMX1 kd + NOX4 kd=793, TMX1 kd + GKT=844).",
    "ncbi_link": "NOX4: 50507
TMX1: 81542"
  },
  {
    "caption": "Proliferation (48 h) of melanoma cell lines measured after transient knockdown of TMX1 or TMX3.",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Proliferation (48 h) of melanoma cell lines with stable TMX1 knockdown (two clones).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Proliferation (24 h) of melanoma cell lines after transient knockdown of NFAT1.",
    "ncbi_link": "NFAT1: 4773"
  },
  {
    "caption": "Proliferation of WM3734 48 h after transient knockdown of TMX1 and treatment with NAC (100 µM) or mTEMPO (100 nM).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Transwell migration (48 h) of WM3734 after transient knockdown of TMX1 or TMX3.",
    "ncbi_link": "TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Transwell migration (48 h) of WM3734 after transient knockdown of TMX1 and treatment with NAC (100 µM) or mTEMPO (1 µM).",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Invasion of WM3734 with stable TMX1 knockdown (two clones) through Matrigel for 96 h.",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Mouse xenograft model to assess tumor growth of WM3734 with stable TMX1 knockdown (TMX1 kds; two clones) in immunodeficient mice. (I) Tumor growth in the first 19 days after injection; (J) the corresponding tumor volume quantified after 19 days and (K) after 45 days.",
    "ncbi_link": "TMX1: 81542"
  },
  {
    "caption": "Kaplan-Meier survival plots and log rank for the correlation between mRNA expression levels and survival probability of melanoma patients, separated in groups with high or low expression of any of the three genes of interest (GOI), TMX1, TMX3 and NFAT1.",
    "ncbi_link": "NFAT1: 4773
TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "mRNA expression levels of NFAT1, TMX1 and TMX3 in BRAF WT and BRAF V600E melanoma patients. In (B), expression levels are based on the FPKM values of the TCGA samples (center line: median; box: 25 % and 75 % percentile; whiskers: 1.5 times interquartile range).",
    "ncbi_link": "BRAF: 673
NFAT1: 4773
TMX1: 81542
TMX3: 54495"
  },
  {
    "caption": "Kaplan-Meier survival plots and log rank for the correlation between mRNA expression levels and survival probability of melanoma patients, separated in groups with (C) BRAF WT and (D) BRAF V600E and with high or low expression of NFAT1.",
    "ncbi_link": "BRAF: 673
NFAT1: 4773"
  },
  {
    "caption": "(D-E) Subcellular  localization  of  Ams1 (D) and Ape4 (E). Wild-type (WT), nbr1Δ, sst4Δ, and atg1Δ cells were grown to mid-log phase in EMM medium and examined by  live cell imaging. In (D), Ams1 was endogenously tagged at its C-terminus with mCherry. In (E), Ape4  was endogenously tagged at its C-terminus with GFP and in the same cells GFP-binding-protein (GBP) fused 3xUb was expressed under the P41nmt1  promoter. Cpy1 is a vacuole lumen marker. Scale bar, 3 μm.",
    "ncbi_link": "atg1: 2539461
nmt1: 2539108
nbr1: 2541353
sst4: 2542403"
  },
  {
    "caption": "Localization  of  Ams1 in WT, lap2Δ, ape2Δ, and ape4Δ cells. Scale bar, 3 μm.   Localization of Ape4 in WT, lap2Δ, ape2Δ, and ams1Δ cells. Scale bar, 3 μm.   ",
    "ncbi_link": "ape4: 2543605
ams1: 2543485
ape2: 2540648
lap2: 2538917"
  },
  {
    "caption": "The ZZ1 region but not the ZZ2-ZZ3 region in  Nbr1 is necessary for vacuolar  targeting of  Ams1. Scale bar, 3 μm.   The ZZ1 region but not the ZZ2-ZZ3 region in Nbr1  is necessary for vacuolar targeting of Ape4. Scale bar, 3 μm.   The ZZ2-ZZ3 region but not the ZZ1 region in Nbr1 is necessary for  vacuolar targeting of Ape2. Scale bar, 3 μm.   The ZZ2-ZZ3 region but not the ZZ1 region in Nbr1 is necessary for vacuolar  targeting of  Lap2. Scale bar, 3 μm.   ",
    "ncbi_link": "Nbr1: 2541353"
  },
  {
    "caption": "Surface plasmon resonance (SPR) analysis of the  Nbr1-Ams1 interaction. GST-tagged ZZ1-L1 fragment of Nbr1 purified from E. coli was captured on a CM5 sensor chip using the GST Capture Kit. Ams1 purified from S. pombe (two-fold serial dilutions from 1000 nM to 62.5 nM) was flowed through the chip surface.",
    "ncbi_link": "Nbr1: 2541353"
  },
  {
    "caption": "SPR  analysis of the Nbr1-Ape4 interaction.  GST-tagged ZZ1-L1 fragment of Nbr1 purified from E. coli was captured on a CM5 sensor chip using the GST Capture Kit. Ape4 purified from  S. pombe (two-fold serial dilutions from 1000 nM to 62.5 nM) was flowed through the chip surface.",
    "ncbi_link": "Nbr1: 2541353"
  },
  {
    "caption": "The effects of individually mutating the first two residues of Ams1 on its Nbr1-binding ability. Nbr1-Ams1 interactions were examined by the Pil1 co-tethering assay. Scale bar, 3 μm.",
    "ncbi_link": "Ams1: 2543485"
  },
  {
    "caption": "The effects of individually mutating the third residue and other residues in the U-shaped loop of Ape4 on its  Nbr1-binding ability. Nbr1-Ape4 interactions were examined by the Pil1 co-tethering assay. Scale bar, 3 μm.",
    "ncbi_link": "Ape4: 2543605"
  },
  {
    "caption": "A Effects of myeloid-specific Lamtor1 deficiency on peritoneal IL-1β production, CD11b+ Ly6C+ monocyte recruitment, and CD11b+ Ly6G+ neutrophil recruitment after an intraperitoneal injection of 600 μL alum solution (20 mg/mL, 6 h), Data are shown as means ± SEM. * indicates P < 0.05 and *** indicates P < 0.001 by Student's t-test, n = 6 mice (peritoneal IL-1β production) and 4 mice (FACS analysis).",
    "ncbi_link": "Lamtor1: 66508"
  },
  {
    "caption": "B Effects of myeloid-specific Lamtor1 deficiency in an acute gouty arthritis model. MSU crystals (0.5 mg) or the PBS control were injected intra-articularly into the tibia-tarsal joint of Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre mice. Mice were assessed for joint swelling using electronic calipers. Images show photomicrographs (upper panel) and hematoxylin and eosin-stained sections (middle and lower panels) of ankle joints obtained at 24 h. Data are shown as the means ± SEM. *** indicates P < 0.001 by Student's t-test, n = 7 mice each.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "C Effects of Lamtor1 deficiency on IL-1β secretion after NLRP3 inflammasome activation or TLR ligand stimulation. ELISA assay shows IL-1β secretion in supernatants from Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs treated with LPS (200 ng/mL, 4 h), followed by nigericin (15 μM, 1 h), ATP (10 mM, 1 h), or GPN (100 nM, 6 h).",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "D Effects of Lamtor1 deficiency on IL-1β secretion after NLRP3 inflammasome activation in human THP-1 monocytes. ELISA assay shows IL-1β secretion in supernatants from WT cells, Lamtor1 KO different single clones, all of which were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight).",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "E, F Effects of Lamtor1 deficiency on IL-1β secretion after the induction of endogenous ROS by mitochondrial poisons or the administration of an exogeneous ROS (hydrogen peroxide). ELISA assay shows IL-1β secretion in supernatants after treatment with LPS (200 ng/mL), Rotenone (10 μM), or Antimycin (10 μg/mL) for 6 h or followed by hydrogen peroxide (3.86 mM).",
    "ncbi_link": "Lamtor1: 66508"
  },
  {
    "caption": "G Effects of Lamtor1 reconstitution in Lamtor1-deficient macrophages on IL-1β secretion after NLRP3 inflammasome activation. ELISA assay shows IL-1β secretion in BMDM supernatants from Lamtor1flox/flox cells, Lamtor1flox/flox LysM-Cre cells, and Lamtor1flox/flox LysM-Cre cells reconstituted with full-length Lamtor1, all of which were treated with nigericin (15 μM, 1 h) after priming with LPS (200 ng/mL, 4 h).",
    "ncbi_link": "Cre: 2777477
Lamtor1: 55004
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "H Effects of Lamtor1 deficiency on IL-1β secretion after NLRP3 inflammasome activation in human THP-1 monocytes. ELISA assay shows IL-1β secretion in supernatants from WT cells, Lamtor1 KO cells, and Lamtor1 KO cells reconstituted with full-length Lamtor1, all of which were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight) and LPS (200 ng/mL, 2 h).",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "I Effects of Lamtor1 deficiency on IL-18 secretion after NLRP3 inflammasome activation in human THP-1 monocytes. ELISA assay shows IL-18 secretion in supernatants from WT cells, Lamtor1 KO cells, and Lamtor1 KO cells reconstituted with full-length Lamtor1, all of which were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight) and LPS (200 ng/mL, 2 h).",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "J Effects of Lamtor1 deficiency on IL-1β secretion after Pyrin inflammasome activation. ELISA assay showing IL-1β secretion in supernatants from Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs treated with TcdB (0.5 μg/mL, 3 h) after LPS (200 ng/mL, 4 h) stimulation.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105
TcdB: 66353157"
  },
  {
    "caption": "K Effects of Lamtor1 deficiency on IL-1β secretion after AIM2 inflammasome activation. ELISA assay showing IL-1β secretion in supernatants from Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs treated with Poly(dA:dT) (5 μg/mL, overnight) and Lipofectamine 3000 after LPS (200 ng/mL, 4 h) stimulation.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "Effects of Lamtor1 deficiency on Caspase-1 processing after NLRP3 inflammasome activation. Western blot shows caspase-1/p10, pro-caspase-1, Lamtor1, and β-actin. Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs (A) (B) were treated with nigericin (15 μM, 1 h) after LPS [200 ng/mL, for 4 h (BMDM) stimulation.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "Effects of Lamtor1 deficiency on Caspase-1 processing after NLRP3 inflammasome activation. Western blot shows caspase-1/p10, pro-caspase-1, Lamtor1, and β-actin. WT and Lamtor1 KO THP-1 cells (B) were treated with nigericin (15 μM, 1 h) after LPS [200 ng/mL 2 h (THP-1)] stimulation.",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "C Effects of Lamtor1 deficiency on GSDMD processing after NLRP3 inflammasome activation. Western blot shows GSDMD, Lamtor1, and β-actin. Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs were treated with nigericin (15 μM, 1 h) after LPS (200 ng/mL, 4 h) stimulation.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "D Effects of Lamtor1 deficiency on pyroptosis after NLRP3 inflammasome activation. Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs were treated with nigericin (15 μM, 1 h) after LPS (200 ng/mL, 4 h) stimulation and the percentage of propidium iodide positive cells were counted by flow-cytometry.",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "E Effects of Lamtor1 deficiency on IL-1β dynamics. Western blot shows IL-1β and β-actin. WT cells and Lamtor1 KO cells were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight) stimulation.",
    "ncbi_link": "Lamtor1: 66508"
  },
  {
    "caption": "F Effects of the active form of GSDMD reconstitution on Lamtor1 KO THP-1 cells. ELISA assay shows IL-1β secretion in supernatants from WT cells, Lamtor1 KO cells, and Lamtor1 KO cells reconstituted with active form of GSDMD, all of which were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight) and LPS (200 ng/mL, 2 h).",
    "ncbi_link": "GSDMD: 79792
Lamtor1: 55004"
  },
  {
    "caption": "G Confirmation of the reconstitution of the active form Caspase-1 (p10 and p20) or GSDMD (GSDMD-NT).",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "H Effects of Lamtor1 deficiency on the priming phase. Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs were treated with treated with LPS (200 ng/mL, 4 h).",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "I Effects of IL-1β and active form of Caspase-1 reconstitution on Lamtor1 KO THP-1 cells. ELISA assay shows IL-1β secretion in supernatants from WT cells, Lamtor1 KO cells, and Lamtor1 KO cells reconstituted with IL-1β, active form of Caspase-1, all of which were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight) and LPS (200 ng/mL, 2 h).",
    "ncbi_link": "Caspase-1: 834
IL-1β: 3553
Lamtor1: 55004"
  },
  {
    "caption": "A Representative images of mutant Lamtor1. PMA-primed Lamtor1 KO THP-1 macrophages reconstituted with full-length or truncated Lamtor1.",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "B Effects of the Lamtor1 point mutation on IL-1β secretion after NLRP3 inflammasome activation. ELISA assays show IL-1β secretion in THP-1 cell supernatants from WT cells, Lamtor1 KO cells and Lamtor1 KO cells reconstituted with full-length Lamtor1 or variants of Lamtor1 in which G2 was replaced with alanine (G2A); all cell types were then treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight).",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "C Effects of Lamtor1 deficiency on mTORC1 activity. Immunoblot analysis of Lamtor1flox/flox and Lamtor1flox/flox LysM-Cre BMDMs treated with LPS (200 ng/mL, 4 h).",
    "ncbi_link": "Cre: 2777477
Lamtor1: 66508
LysM: 17105"
  },
  {
    "caption": "Co-immunoprecipitation assay showing the interaction between Lamtor1 and HDAC6. Immunoblot analysis of Lamtor1-Flag co-immunoprecipitated with HDAC6-myc from lysates of HEK293T cells transfected with the indicated plasmids",
    "ncbi_link": "Flag: 
myc: 
HDAC6: 10013
Lamtor1: 55004"
  },
  {
    "caption": "Co-immunoprecipitation assay showing the interaction between Lamtor1 and HDAC6. Immunoblot analysis of Lamtor1-Flag co-immunoprecipitated with HDAC6-myc from lysates of HEK293T cells transfected with the indicated plasmids",
    "ncbi_link": "Flag: 
myc: 
HDAC6: 10013
Lamtor1: 55004"
  },
  {
    "caption": "Co-immunoprecipitation assay showing the interaction between Lamtor1 and HDAC6. Lamtor1-Flag co-immunoprecipitated with endogenous HDAC6 from the lysate of Lamtor1-Flag knocked-in THP-1 cells. (D)",
    "ncbi_link": "Flag: 
Lamtor1: 55004"
  },
  {
    "caption": "Endogenous Lamtor1 co-immunoprecipitated with endogenous HDAC6 from lysates of WT THP-1 cells Effects of NLRP3 inflammasome activation on the interactions between Lamtor1 and HDAC6. Co-immunoprecipitation assay shows interactions between Lamtor1 and HDAC6.",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "Endogenous Lamtor1 co-immunoprecipitated with endogenous HDAC6 from lysates of WT THP-1 cells Effects of NLRP3 inflammasome activation on the interactions between Lamtor1 and HDAC6. Co-immunoprecipitation assay shows interactions between Lamtor1 and HDAC6.",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "H NanoBRET assay to confirm endogenous binding between Lamtor1 and HDAC6 in living cells. HEK293T cells were transiently transfected with NanoLuc-fused Lamtor1 and Halo-tag-fused HDAC6 using Lipofectamine 2000. Luminescence was measured 48 h after transfection following the addition of Nano-Glo Luciferase Assay Substrate (Promega).",
    "ncbi_link": "Halo: 
Luc: 
HDAC6: 10013
Lamtor1: 55004"
  },
  {
    "caption": "I Immunoblot analysis of the truncated form of Flag-tagged Lamtor1 mutant (∆145-161, Met1-144; ∆95-161, Met1-Val94) co-immunoprecipitated with HDAC6-myc from lysates of HEK293T cells transfected with the indicated plasmids.",
    "ncbi_link": "Flag: 
Lamtor1: 55004"
  },
  {
    "caption": "Effect of truncated Lamtor1 mutant on NLRP3 inflammasome activation in THP-1 cells. ELISA assay showing IL-1β secretion in supernatants from WT cells, Lamtor1 KO cells, Lamtor1 KO cells reconstituted with full-length Lamtor1, and Met1-Val94 Lamtor1 cells; all cell types were treated with nigericin (15 μM, 1 h) after priming with PMA (50 nM, overnight).",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "C, D Immunoblot analysis of Lamtor1-V5 co-immunoprecipitated with NLRP3-Flag from lysates of HEK293T cells transfected with the indicated plasmids.",
    "ncbi_link": "Flag: 
V5: 
Lamtor1: 55004
NLRP3: 114548"
  },
  {
    "caption": "Immunoblot analysis of the truncated form of V5-tagged Lamtor1 mutant (∆145-161, Met1-Ser144) co-immunoprecipitated with NLRP3-flag from lysates of HEK293T cells transfected with the indicated plasmids.",
    "ncbi_link": "flag: 
V5: 
Lamtor1: 55004
NLRP3: 114548"
  },
  {
    "caption": "Immunoblot analysis of the truncated form of V5-tagged Lamtor1 mutant (∆145-161, Met1-Ser144) co-immunoprecipitated with NLRP3-flag from lysates of HEK293T cells transfected with the indicated plasmids.",
    "ncbi_link": "flag: 
V5: 
Lamtor1: 55004
NLRP3: 114548"
  },
  {
    "caption": "G Effect of the HDAC6 knockdown on NLRP3-Lamtor1 interactions. Immunoblot analysis of Lamtor1-V5 co-immunoprecipitated with NLRP3-Flag from lysates of HEK293T cells transfected with the indicated plasmids.",
    "ncbi_link": "Flag: 
V5: 
HDAC6: 10013
Lamtor1: 55004
NLRP3: 114548"
  },
  {
    "caption": "C Effects of Lamtor1 deficiency on ASC speck formation after NLRP3 inflammasome activation. Representative images of PMA-primed THP-1 macrophages stably expressing GFP-tagged ASC treated with or without LPS (200 ng/mL, 2 h) and nigericin (15 μM, 1 h). Scale bars = 10 μm.",
    "ncbi_link": "Lamtor1: 55004"
  },
  {
    "caption": "Effects of DL-all-rac-α-tocopherol on the interactions between Lamtor1 and HDAC6. Immunoblot analysis of Lamtor1-Flag co-immunoprecipitated with HDAC6-myc from lysates of HEK293T cells transfected with the indicated plasmids after pretreatments with the DL-all-rac-α-tocopherol (B)",
    "ncbi_link": "Flag: 
myc: 
HDAC6: 10013
Lamtor1: 55004"
  },
  {
    "caption": "Effects of α-tocopherol on the interactions between Lamtor1 and HDAC6. Immunoblot analysis of Lamtor1-Flag co-immunoprecipitated with HDAC6-myc from lysates of HEK293T cells transfected with the indicated plasmids after pretreatments with the D -α-tocopherol (E)",
    "ncbi_link": "Flag: 
myc: 
HDAC6: 10013
Lamtor1: 55004"
  },
  {
    "caption": "a, Protein extracts from drpr null (w; drpr∆5/drpr∆5) pupae at puparium formation (0 h) and wild-type (Canton-S) salivary glands6 h, 12 h and 14 h after puparium formation, analysed by western blotting with anti-Drpr antibody.",
    "ncbi_link": "drpr: 38218"
  },
  {
    "caption": "b, Samples from control animals (+/w; +/drpr∆5), n = 12, and drpr null mutants (w; drpr∆5/drpr∆5), n = 47, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation. c, Quantification of data from b and d. d, Samples from control animals (+/w; +/UAS-drprIR), n = 11, and those with salivary gland-specific knockdown of drpr (fkh-Gal4/w; UAS-drprIR/+), n = 19, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation.",
    "ncbi_link": "Gal4: 
drpr: 38218"
  },
  {
    "caption": "e, Control animals (+/w; +/UAS-drpr-IIR), n = 9, and those with salivary gland-specific knockdown of drpr-I (fkh-Gal4/w; UAS-drpr-IIR/+), n = 20, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation. f, Quantification of data from e.",
    "ncbi_link": "Gal4: 
drpr: 38218"
  },
  {
    "caption": "g, Samples from drpr null animals (+/w; +/UAS-Drpr-I; drpr∆5/drpr∆5), n = 9, and those with salivary gland-specific expression of Drpr-I (fkh-Gal4/w; UAS-Drpr-I/+; drpr∆5/drpr∆5), n = 20, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation. h, Quantification of data from g.",
    "ncbi_link": "Gal4: 
drpr: 38218
Drpr: 38218"
  },
  {
    "caption": "a, Samples from animals with salivary gland-specific expression of p35 (fkh-Gal4/+; UAS-p35/+), n = 18 (left), drpr null animals (+/w; +/UAS-p35; drpr∆5/drpr∆5), n = 10 (middle), and drpr null animals with salivary gland-specific expression of p35 (fkh-Gal4/w; UAS-p35/+; drpr∆5/drpr∆5), n = 16 (right), analysed by histology for the presence of salivary gland material 24 h after puparium formation. Red circles, cell fragments; yellow circle, gland fragments.",
    "ncbi_link": "Gal4: 
p35: 
drpr: 38218"
  },
  {
    "caption": "a, Samples from animals with salivary gland-specific expression of p35 (fkh-Gal4/+; UAS-p35/+), n = 18 (left), drpr null animals (+/w; +/UAS-p35; drpr∆5/drpr∆5), n = 10 (middle), and drpr null animals with salivary gland-specific expression of p35 (fkh-Gal4/w; UAS-p35/+; drpr∆5/drpr∆5), n = 16 (right), analysed by histology for the presence of salivary gland material 24 h after puparium formation. Red circles, cell fragments; yellow circle, gland fragments. b, Quantification of data from a.",
    "ncbi_link": "Gal4: 
p35: 
drpr: 38218"
  },
  {
    "caption": "c, Salivary glands dissected from animals expressing drprIR specifically in GFP-marked clone cells (heat shock (hs)flp/w; UAS-drprIR/+; act,cd2, FRT > Gal4, UAS-GFP/+) 6 h and 14 h after puparium formation. Stained with GFP antibody (green), to label cells expressing drpr IR, and Lamin antibody (red).",
    "ncbi_link": "Gal4: 
drpr: 38218"
  },
  {
    "caption": "a, Samples from animals with salivary gland-specific knockdown of Atg12 (fkh-Gal4/w; UAS-Atg12IR/+), n = 21, and those with salivary gland-specific knockdown of both Atg12 and drpr-I (fkh-Gal4/w; UAS-Atg12IR/+; UAS-drpr-IIR/+), n = 19, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation. b, Quantification of data from a.",
    "ncbi_link": "Gal4: 
Atg12: 39383
drpr: 38218
fkh: 43383"
  },
  {
    "caption": "c, GFP-LC3 was expressed in salivary glands of control animals (+/w; UAS-GFP-LC3/+; fkh-Gal4/+) and those with salivary gland-specific knockdown of drpr (w; UAS-drprIR/UAS-GFP-LC3; fkh-Gal4/+). Salivary glands were dissected 6 h and 14 h after puparium formation, imaged for GFP-LC3, and LC3 puncta were quantified using Zeiss Automeasure software. d, Quantification of data from c. Error bars represent s.e.m.; n ≥ 10; p  0.0000001.",
    "ncbi_link": "Gal4: 
drpr: 38218"
  },
  {
    "caption": "e, LAMP1-GFP was expressed in control animals (tub-LAMP-GFP/w; +/fkh-Gal4) and those with salivary gland-specific knockdown of drpr (tub-LAMP-GFP/w; UAS-drprIR/+; fkh-Gal4/+). Salivary glands were dissected 14 h after puparium formation, imaged for LAMP-GFP, and LAMP puncta were quantified using Zeiss Automeasure software. f, Quantification of data from e. Error bars represent s.e.m.; n ≥ 10; p  0.05.",
    "ncbi_link": "Gal4: 
tub: 
drpr: 38218
LAMP: 35411"
  },
  {
    "caption": "g, Samples from drpr mutant animals (+/w; +/UAS-Atg16A; drprDgr;5/drprDgr;5), n = 10, and those with salivary gland-specific expression of Atg16A (fkh-Gal4/w; UAS-Atg16A/+; drprDgr;5/drprDgr;5), n = 16, analysed by histology for the presence of salivary gland material (red circles) 24 h after puparium formation. h, Quantification of data from g.",
    "ncbi_link": "Gal4: 
Atg16A: 326115
drpr: 38218"
  },
  {
    "caption": "a, Protein extracts from drpr null (w; drprDgr;5/drprDgr;5) pupae at puparium formation (0 h) and from the fat bodies of wild-type (Canton-S) third-instar larvae were analysed by western blotting with anti-Drpr antibody. Third-instar larvae were either fed or starved for 4 h.",
    "ncbi_link": "drpr: 38218"
  },
  {
    "caption": "c, We starved third-instar larvae expressing GFP-Atg8a in all cells, and drprIR specifically in dsRed-marked clone cells (hsflp/w; UAS-drprIR/+; hsGFPAtg8a, act,cd2, FRT > Gal4, UAS-dsRed/+), for 4 h. We dissected larval fat bodies and imaged them for GFP-Atg8a (green) and dsRed (red).",
    "ncbi_link": "Gal4: 
act: 5656844
Atg8a: 32001
drpr: 38218"
  },
  {
    "caption": "d, Salivary glands of animals expressing GFP-Atg8a in all cells, and drprIR specifically in dsRed-marked clone cells (hsflp/w; UAS-drprIR/+; hsGFPAtg8a, act,cd2, FRT > Gal4, UAS-dsRed/+), dissected 14 h after puparium formation. Imaged for GFP-Atg8a (green) and dsRed (red). We stained nuclei with Hoechst (blue).",
    "ncbi_link": "Gal4: 
act: 5656844
Atg8a: 32001"
  },
  {
    "caption": "A Growth of indicated Y. pestis strains in zinc-limited medium (cPMH2) (n=3). B Growth of indicated Y. pestis strains in zinc-replete medium (cPMH2 + 10μM ZnCl2) (n=3). Data information: One-way ANOVA with Dunnett test, *p≤0.05, **p≤0.001, ****p≤0.0001. For A, B growth of mutants was compared to znuBC. Data represents the mean ±SD of three biological replicates. For some points, error bars are too small to visualize on the graph.",
    "ncbi_link": "znuB: "
  },
  {
    "caption": "D Growth of znuBC y0702-y0703, znuBC y0704, or y0702-y0703 complemented mutant (pBCSK+y0702-70703) in zinc-limited medium (cPMH2) (n=3). Data information: One-way ANOVA with Dunnett test, *p≤0.05, **p≤0.001, ****p≤0.0001. D, growth of mutants was compared to znuBC. Data represents the mean ±SD of three biological replicates. For some points, error bars are too small to visualize on the graph.",
    "ncbi_link": "znuB: "
  },
  {
    "caption": "B Growth of znuBC irp2 pGENlux in co-culture with indicated Y. pestis strains in zinc-limited medium (cPMH2) (n=3). Data information: For B, Data represents the mean ±SD relative luminescent units (RLU) from three biological replicates. For some points, error bars are too small to visualize on the graph. One-way ANOVA with Dunnett test compared to znuBC irp2 + Y. pestis; ****p≤0.0001.",
    "ncbi_link": "irp2: 
znuB: "
  },
  {
    "caption": "Growth of indicated Y. pestis strains in zinc-limited medium (cPMH2) (n=3), One-way ANOVA with Dunnett test compared to znuBC mutant, **p≤0.01, ****p≤0.0001. Data represents the mean ±SD of three biological replicates. For some points, error bars are too small to visualize on the graph.",
    "ncbi_link": "znuB: "
  },
  {
    "caption": " B) Levels of TIMP1, MMP7 and TSP2 in plasma of healthy mice (n=15), mice with chronic pancreatitis at 150 days of age (n=19), KC mice at 330 days of age (control PdxCre n=3-4; KC n=7-8), KPC mice at 150 days of age (control PdxCre n=4-7; KPC n=4). The exact n is indicated in Appendix Table S3B. Box plots extends from 25th to 75th percentiles, whiskers extends from min to max and horizontal lines indicate median. p-values were calculated with 1-way ANOVA with Tukey"s multiple comparison test ",
    "ncbi_link": "PdxCre: "
  },
  {
    "caption": " C) Histological analysis of pancreas from PdxCre and KC mice with different grades of PanIN lesions at 330 days of age. Anti-TIMP1, anti-MMP7, anti-TSP2 and anti-CCN2 staining of a representative KC PanIN lesion (200X, scale bars: 100μm) ",
    "ncbi_link": "PdxCre: "
  },
  {
    "caption": " The cell proliferation assay in HCT116 CRC cells shows growth advantage conferred by the SMARCB1 R377C mutation compared with the wild type SMARCB1 or the vector control. The error bars designate the standard deviation (SD) ",
    "ncbi_link": "SMARCB1: 6598"
  },
  {
    "caption": " The cell proliferation assay in HCT116 CRC cells shows growth advantage conferred by the expression of the wild type STK38L, whereas the R105W mutant only slightly increased the number of colonies. The error bars designate the standard deviation (SD) ",
    "ncbi_link": "STK38L: 23012"
  },
  {
    "caption": "B. Quantification of time-course nucleosome H2A-Ub assays using the indicated BRCA1/BARD1 truncations. Data are presented as the normalized fraction of H2A consumed during a time-course nucleosome ubiquitylation assay. Data points represent mean values and error bars are ± 1-s.d. of n=3 independent technical replicate experiments. The residue bounds of BRCA1RING are 1-112, and BARD1RING are 26-140. Additional details about all reagents used in these studies can be found in the methods section.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "C. Nucleosome binding curves from fluorescence-quenching-based measurements using the indicated BRCA1/BARD1 constructs. Data show mean values and error bars are ± 1-s.d. of n=4 independent technical replicate experiments. The reported difference in affinities to BRCA1RING/BARD1RING is likely underestimated, as the minimal RING/RING heterodimer binding data was collected at a lower ionic strength than the other constructs to obtain well-behaved binding data (50 mM vs. 100 mM NaCl).",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "C. Representative SDS-PAGE gel monitoring in-gel fluorescence (labelled DNA) of UV-induced Bpa crosslinking of the E3 ligase fusion BRCA1-ƒ-BARD1221 (BCƒBD) to nucleosomes (left). In this construct, the C-terminus of BRCA11-104 is genetically fused to the N-terminus of BARD126-221 via a 12-residue GlySer-linker. Quantification of Bpa crosslinking experiments with nucleosomes (right). The intensity of each crosslinked band was normalized to the intensity of the L120Bpa crosslinked band for each replicate experiment. Graph bars show the mean; error bars are ± 1-s.d. and the open circles are the values of individual replicates for of n=3 independent technical replicate experiments.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "Quantification of H2A-Ub time-course assays using the indicated BRCA1/BARD1 constructs. Data show the mean; error bars are ± 1-s.d. of n=3 independent technical replicate experiments.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "Two single time-points from panel C from the BRCA1RING/BARD1RING curve were excluded from analysis due to their extremely low activities coupled with quenching/loading errors yielding normalized fraction of H2A consumed values of <0. Values for these excluded points are included as source data.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "F. Single time-point H2A-Ub inhibition assays using heterodimers containing BRCA1RING/BARD1FL (left, 12 min endpoint) or the indicated BARD1 internal deletion mutant (middle and right, 20 min endpoint) and increasing amounts of dsDNA or bubble-DNA competitor. The same E3 concentration (50 nM) was used for each BRCA1/BARD1 truncation. A longer time point was used for the double-deletion mutant as the intrinsic H2A-Ub activity of this mutant was lower, likely due to the deletion of DNA binding regions.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "A. Western blot analysis to detect HA-BARD1 in nuclei isolated from HeLa-shBARD1 cells stably expressing wild-type or Δ194-216 mutant of HA-BARD1, where endogenous BARD1 was depleted by doxycycline-induced shBARD1 expression. The nuclei were salt-fractionated into NS100, NS300, NS420, and NP420 to assess the amount of HA-BARD1 associated with chromatin. Data are representative of n=2 biological replicate experiments.",
    "ncbi_link": "HA: 
BARD1: 580"
  },
  {
    "caption": "C. Clonogenic survival of HeLa-shBARD1 cells stably expressing wild type or Δ194-216 mutant of HA-BARD1 upon treatment with indicated amount of olaparib and cisplatin. Data points show the mean; error bars represent SEM of n=3 biological replicate experiments.",
    "ncbi_link": "HA: 
BARD1: 580"
  },
  {
    "caption": "B, C. Quantification of time-course H2A-Ub assays using the indicated BRCA1/BARD1 constructs and chromatin substrates. data show the mean; error bars are ± 1-s.d. of n=3 independent technical replicate experiments.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "D. Quantification of time-course H2A-Ub assays using homogenously modified H2A K15-Ub mono-nucleosome substrates and indicated BRCA1/BARD1 constructs. data show the mean; error bars are ± 1-s.d. of n=3 independent technical replicate experiments. One time-point from Panel D was determined to be an outlier due to a reaction quenching error and excluded from analysis. The excluded value is reported as source data.",
    "ncbi_link": "BARD1: 580
BRCA1: 672"
  },
  {
    "caption": "G, H. Quantification of time-course H2A-Ub assays using the indicated combinations of di-NCP substrate and BRCA1/BARD1 heterodimer. In each case, the y-axis reports on the fraction of H2Aobserve (as shown in Panel F). Lower E3 concentrations were used in these reactions than in those presented in Figure 1 using unmodified mono-nucleosome substrates (15 nM vs. 100 nM), accounting for the slower observed H2A-Ub kinetics for the unmodified di-nucleosome substrate. data show the mean; error bars are ± 1-s.d. of n=3 independent technical replicate experiments.",
    "ncbi_link": "BARD1: 580
BRCA1: 672
H2A: 3012///317772///8335///8338///85235///8337///8336///92815///3013///8330///8331///8332///8334///25763///55766///94239///83740///8329///3015///474382///474381///8969///3014"
  },
  {
    "caption": "A Coolness stimulates intracellular cyclic guanosine monophosphate (cGMP) accumulation in HEK‐293T cells expressing GC‐G. Two days after transfection of empty vector or GC‐G‐encoding plasmid, cells were exposed to ambient temperatures (37 or 15°C) for 20 min and cellular cGMP concentration was measured.",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "B Temperature dependence of GC‐G activity. Membrane preparations from HEK‐293T cells transfected with empty vector or GC‐G‐encoding plasmid were used to determine cyclase activity at the indicated temperatures for 20 min (asterisks denote values significantly elevated compared to 37°C).",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "C GC‐G is the only murine transmembrane GC that can be stimulated by cool temperatures. Expression plasmids encoding FLAG‐tagged GC subtypes GC‐A to GC‐G were transfected into HEK‐293T cells. Two days after transfection, membrane protein fractions were prepared and used for cyclase activity assays at 37 or 15°C. Protein expression of each receptor GC was confirmed by Western blot (WB) analysis with anti‐FLAG antibody.",
    "ncbi_link": "GC‐A: 14913
GC‐G: 73707"
  },
  {
    "caption": "D The H+CYC domain is critical for stimulation by coolness. The domain structure of full‐length (FL) GC‐G and its mutant variants is shown in the upper panel. A FLAG tag was added at the N‐terminus of each protein. The ΔECD+KLD mutant protein lacks amino acids 73-455 and 556-833; the ΔCYC variant lacks amino acids 834-1,003. The H+CYC mutant protein contains amino acids 806-1,100. ECD, extracellular domain; KLD, kinase‐like domain; SP, signal peptide; TM, transmembrane region. HEK‐293T cells expressing the indicated GC‐G constructs were incubated at 37 or 15°C for 20 min, then intracellular cGMP concentration was measured (lower panel).",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "In the chimeric GC‐A/G protein, the H+CYC domain of GC‐A was replaced by that of GC‐G (upper panel). HEK‐293T cells expressing the indicated proteins were exposed to ambient temperature of 37 or 15°C for 20 min; then, intracellular cGMP concentration was measured. Data are mean ± SD from three experiments in triplicate. **P 0.01.",
    "ncbi_link": "GC‐A: 14913
GC‐G: 73707"
  },
  {
    "caption": "B, C Protein expression and coolness‐stimulated cGMP synthesis of the above shown divergent C‐terminal fragments of GC‐G with intact or ablated hinge (H) region. The expression plasmids encoding the H+CYC domain or a deletion construct (Δ1-Δ2) tagged with a FLAG epitope were transfected into HEK‐293T cells. Two days after transfection, cells were exposed to the ambient temperatures (37 or 15°C) for 20 min and cellular cGMP concentration was measured (C). Protein expression of each construct was confirmed by Western blot (WB) analysis with anti‐FLAG antibody (B).",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "A HEK‐293T cells were co‐transfected with plasmids encoding two differential epitope‐tagged (FLAG or Myc) versions of GC‐G or GC‐A, respectively. After 2 days, transfected cells were lysed with detergent and lysates were subjected to immunoprecipitation (IP) for 2 h with anti‐Myc antibody at two different temperatures (15 or 25°C), followed by Western blotting (WB) using anti‐FLAG antibody to determine the amount of dimerized/oligomerized GC proteins (upper panel). These approaches demonstrated that in contrast to GC‐A, homomeric protein/protein association of GC‐G seems to be enhanced by cool temperatures (upper panel). Cell lysates were also precipitated and immunoblotted with the anti‐Myc antibody, demonstrating that cooling does not interfere with immunoprecipitation of Myc‐tagged GC‐G via the anti‐Myc antibody (middle panel). Likewise, precipitation and immunoblotting with the anti‐FLAG antibody yielded bands of similar intensity for 15 and 25°C, respectively (lower panel).B Relative quantification of homomeric protein/protein association of GC‐G and GC‐A was performed by densitometric scanning. Each intensity value from the upper panel was subsequently normalized to the total protein levels as determined in the middle and the lower panel of Fig A (intensity of the immunoreactive bands obtained with the anti‐Myc or anti‐FLAG antibody, respectively). Relative dimerization level at 15°C was further calculated by normalizing to values obtained at 25°C; the latter were set as 1. Results are means ± SD of three experiments, **P 0.01 (compared to 25°C).",
    "ncbi_link": "GC‐A: 14913
GC‐G: 73707"
  },
  {
    "caption": "HEK‐293T cells expressing CNGA3 alone (upper panel) or together with GC‐G (full‐length in the middle panel and H+CYC domain in the lower panel) were loaded with the Ca2+ indicator Fura‐2 to monitor intracellular [Ca2+]i concentration. Cells co‐expressing GC‐G and CNGA3 showed a rapid increase in [Ca2+]i when the temperature was lowered from 37 to 15°C (middle and lower panel); cells only expressing CNGA3 are not responsive to cool temperatures (top panel). Removal of extracellular Ca2+ (−Ca2+; middle panel) completely suppressed the response to cooling. ΔF represents changes in the ratio of the fluorescence intensity of Fura‐2 at 340/380 nm excitation. The ratiometric Ca2+ responses are representative of 30 cells recorded from three experiments.",
    "ncbi_link": "CNGA3: 12790
GC‐G: 73707"
  },
  {
    "caption": "A-H In situ hybridization experiments with an antisense probe for c‐Fos on coronal sections through the GG of wild‐type (WT; left panel) or GC‐G‐KO (right panel) mouse pups (P0-P4) exposed to warm (35°C; A-D) or cool (22°C; E-H) ambient temperature for 2 h. Panels (C, D, G, H) show higher magnifications of the boxed areas in (A, B, E, F). At 35°C (A-D), no c‐Fos expression was detectable in the GG of both WT (A, C) and GC‐G‐KO (B, D) individuals. Upon exposure to 22°C, strong c‐Fos expression was observed in the GG of WT pups (E, G), whereas c‐Fos expression was barely detectable in the GG of GC‐G‐KO animals (F, H). The data shown are representative of 10 independent experiments. Pups originated from six different litters for each genotype. Scale bars: 200 μm in (A, B, E, F); 50 μm in (C, D, G, H).I Quantification of c‐Fos‐positive GG cells in WT and GC‐G‐KO pups on exposure to 22°C for 2 h. All stained cells on every section along the rostrocaudal extent of the GG were counted; the results shown are based on the above‐mentioned 10 experiments. The number of c‐Fos‐positive cells in the GG of a GC‐G‐KO mouse was determined relative to that in a concomitantly processed WT pup; the latter number was set to 100%. Data are mean ± SD (n = 11 in each genotype), **P 0.0001.",
    "ncbi_link": "c‐Fos: 14281
GC‐G: 73707"
  },
  {
    "caption": "J-N Calcium imaging of coronal sections through the GG of olfactory marker protein‐green fluorescent protein (OMP‐GFP)/GC‐G+/+ or OMP‐GFP/GC‐G‐KO pups (P1-P4). High magnification image (J) of a tissue slice through the GG of an OMP‐GFP pup with GG neurons labeled by intrinsic GFP fluorescence (GFP fluorescence was merged with the transmitted‐light channel). Cells analyzed are circled in blue (GFP‐negative) or red (GFP‐positive). NC, nasal cavity. Scale bar: 30 μm. (K-M) Representative ratiometric Ca2+ transients induced by cooling from 37 to 15°C in GFP‐negative non‐neuronal cells (K) and in GFP‐positive GG neurons from OMP‐GFP/GC‐G+/+ (L) and OMP‐GFP/GC‐G‐KO pups (M). The numbers in the bottom right hand corners are the number of cells with Ca2+ transient similar to what is shown in the respective graph (left) and total number of measured cells (right). (N) Quantification of coolness‐induced ΔF in GG neurons from OMP‐GFP/GC‐G+/+ and OMP‐GFP/GC‐G‐KO mice. Coolness‐induced ΔF was calculated by subtracting the baseline fluorescence ratio (340/380 nm) at 37°C from the peak fluorescence ratio (340/380 nm) measured at 15°C. For OMP‐GFP/GC‐G+/+, the 29 coolness‐responsive neurons (black bar) of all 54 analyzed neurons (gray bar) from five slices (obtained from different animals) were analyzed. For OMP‐GFP/GC‐G‐KO, the 50 analyzed neurons (shaded bar) from five slices (obtained from different animals) were analyzed. Data are mean ± SD, **P 0.01.",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "A Reduced responsive rate of coolness‐stimulated USV in GC‐G‐KO pups. Pups were removed from their littermates and dams at postnatal (P) day 2, 4, and 6 and exposed to 15°C. USV was measured by use of the Anabat SD1 Bat detector. The number of responsive pups versus total number of pups tested for each WT and GC‐G‐KO group at different ages is indicated on the top of each bar. *P 0.05.B, C Total number of USV calls (B) and response latency (C) in GC‐G‐KO and WT pups at P2. The horizontal bars indicate the mean. *P 0.05; **P 0.01.",
    "ncbi_link": "GC‐G: 73707"
  },
  {
    "caption": "(D) Cells were treated with  sodium arsenite (50 µM) for 45 min, followed by recovery in drug-free medium. Kinetics of SG dissolution are reported. Images were taken over a time period of 4 hrs every 10 min. Dashed lines = 95% confidence intervals. Number of cells counted: 159 (siRNA control); 166 (siRNA Hsp90 α+β).",
    "ncbi_link": "Hsp90 α: 3320"
  },
  {
    "caption": "(E) HeLa-Kyoto cells were treated with HS at 43.5˚C for 1 hr. Cells were then allowed to recover at 37 °C for 1 hr in drug-free medium (control) or in presence of VER (40 µM), GA (5 µM) or 17AAG (5 µM). Cells were fixed, stained for the SG marker TIA-1 and the percentage of cells with  SGs was counted. Number of cells counted: 605 (recovery control); 510 (recovery  VER); 1334 (recovery GA); 468 (recovery 17AAG). n = 3-4 independent experiments, ± sem. p < 0.01 (One-way ANOVA). (F) G3BP2-GFP HeLa-Kyoto cells were treated with MG132 (20 µM) for 3 hrs, followed by recovery for 2 hrs in drug-free medium (control) or in presence of  VER (40 µM), GA (5 µM) or 17AAG (5 µM). Cells were fixed and the percentage of cells with SGs was counted.  Number of cells counted: 439 (recovery control); 649 (recovery VER); 637 (recovery GA); 649 (recovery 17AAG). n = 3 independent experiments, ± sem. p < 0.0001 (One-way ANOVA). ",
    "ncbi_link": "GFP: 
G3BP2: 9908"
  },
  {
    "caption": "(C) HeLa cells were subjected to proximity ligation assay (PLA) using antibodies specific for endogenous Hsp90 and DYRK3. PLA foci and nuclei were segmented, and  PLA foci/cell were automatically quantified. The mean of PLA/foci in cells incubated with no antibodies (-), only Hsp90 antibody, only DYRK3 antibody and both Hsp90 and DYRK3 antibodies is shown. Cells incubated with  Hsp90  and DYRK3 antibodies and left untreated were used as control. n = 3 independent experiments, ± sem; 368-504 cells  counted/sample, p < 0.002 between the negative controls and cells incubated with Hsp90 and DYRK3 antibodies; p = 10-6 between cells incubated with  Hsp90 and DYRK3 antibodies and left untreated (control) or treated for 2 hrs with GA (5 µM) (One-way ANOVA). Scale bar is 10 µm.",
    "ncbi_link": "DYRK3: 8444"
  },
  {
    "caption": "(F)  HeLa cells were lipofected with a cDNA encoding for GFP or GFP-DYRK3. 6 hrs post-transfection, cells were incubated in drug-free medium (-) or in presence of GA, 17AAG or VER (concentrations are shown). Total proteins were extracted 16 hrs later. GFP and TUBA4A protein levels were analyzed by immunoblotting. Representative immunoblotting  of 3 independent experiments.",
    "ncbi_link": "GFP: 
DYRK3: 8444"
  },
  {
    "caption": "(I) HeLa cells were lipofected with a cDNA encoding for GFP-DYRK3. 24 hrs post-transfection, cells were treated for 45 min with arsenite (50 µM) alone (control) or with GA (5 µM) or 17AAG (5 µM). Cell were then fixed and the percentage of cells expressing GFP-DYRK3 with SGs was counted. Total cells counted: 462 (sodium arsenite); 444 (sodium arsenite and GA); 561 (sodium arsenite and 17AAG). n = 3 independent experiments, ± sem; p < 0.001 (One-way ANOVA).",
    "ncbi_link": "GFP: 
DYRK3: 8444"
  },
  {
    "caption": "(F) HeLa cells were lipofected with a cDNA encoding for GFP-DYRK3-dN. 24 hrs post-transfection GFP-DYRK3-dN cells were either left untreated or exposed to GA (5 µM) for 4 hrs. In untreated cells (control), GFP-DYRK3-dN is diffusely distributed in the cytosol and in the nucleus. Upon GA treatment, GFP-DYRK3-dN forms perinuclear (PN) aggregates. Representative confocal images are shown. Scale bar is 10 µm.",
    "ncbi_link": "GFP: 
DYRK3: 8444"
  },
  {
    "caption": "(I) mCherry-G3BP1 expressing HeLa cells were lipofected with cDNAs encoding for GFP-DYRK3-dN or Sup35-NM-GFP-DYRK3-dN. 24 hrs post-transfection cells were treated for 45 min with sodium arsenite to induce  SGs, followed by recovery for 4 hrs in presence of  GA  (5 µM; rec. GA). Representative confocal microscopy images are shown. Nucleic acid was stained with DAPI. Scale bar is 10 µm.",
    "ncbi_link": "GFP: 
DYRK3: 8444
Sup35: 851752"
  },
  {
    "caption": "(C) Quantitation of the fluorescence intensity recovery after  bleach of GFP-DYRK3 in G3BP1-mCherry HeLa-Kyoto cells 24 h after transfection. Cells were treated with sodium arsenite (50 µM) for 45 min to induce SGs, which were visualized with G3BP1-mCherry; then, sodium arsenite was removed and the cells were incubated in drug-free medium or in presence of  GA (5 µM) or of GSK  (5 µM). FRAP  was performed during the stress recovery period. A representative  image of cells treated with arsenite followed by recovery in drug-free medium is shown. Arrowheads and dotted circle indicate the ROI. Scale bar is 5 µm. The mean of 13 FRAP curves (recovery control), 12 FRAP curves (recovery GA) and 14 FRAP  curves (recovery GSK) is shown in red; the sem is shown in gray.",
    "ncbi_link": "mCherry: 
G3BP1: 10146"
  },
  {
    "caption": "(B) Confocal microscopy images of  P525L FUS eGFP MNs treated with sodium arsenite  for 2 hrs and showing colocalization of FUS with TIAR-positive stress granules. Scale bar is 10 µm. (C) P525L FUS eGFP MNs were treated with sodium arsenite for 2 hrs, followed by recovery in drug-free medium (+ rec. control) or in presence of 17AAG (30 μM; + rec. 17AAG) or of GSK  (5 μM; +rec. GSK) for 6 hrs. Quantitation of the number of SGs per cell in P525L FUS eGFP MNs. Number  of P525L cells counted and n/condition: 2488, n = 13 (arsenite); 1045, n = 12 (arsenite + rec. control); 646, n = 6 (arsenite + rec.  17AAG); 924, n = 3 (arsenite + rec. GSK), ± sem (One-way ANOVA). ",
    "ncbi_link": "eGFP: 
FUS: 2521"
  },
  {
    "caption": "(I) Double immunofluorescence labeling using antibodies against DYRK3 and FUS in  lumbar spinal cord α-MNs of healthy subjects (control) and fALS patients  carrying the p.521C mutation in the FUS  gene. Control (upper panel): α-MNs showing uniform cytoplasmic (white arrows) and speckled pattern of strong nuclear immunoreactivity (white arrowhead) of DYRK3, as well as diffuse  nuclear FUS immunoreactivity. fALS (p.R521C-FUS; lower panel): surviving α-MNs harboring large FUS aggregates (yellow arrows) showed markedly reduced  DYRK3 immunoreactivity both in the cytoplasm as well as in the  nucleus (red arrowheads). Instead, α-MNs devoid of  FUS  aggregates (white arrows) showed normal DYRK3 immunoreactivity similar to the one of α-MNs from normal controls. Asterix (*) represents non-specific lipofuscin granules in one of the α-MN in FUS-ALS. Paraffin sections; scale bars is 50 µm. (J) Quantification of α-MNs showing low or absent DYRK3 staining (upper graphic) and FUS aggregates (lower graphic) in lumbar spinal cord from five healthy subjects (control) and five  fALS patients carrying the p.521C mutation in the FUS gene. Total number  of α-MNs analyzed: 403 (control); 132 (fALS). n = 5, ± sem (Student's t-test). ",
    "ncbi_link": "FUS: 2521"
  },
  {
    "caption": "(F) RNA immunoprecitation (IP) with anti-GFP antibody in wild-type (mock IP) and nos-Gal4/UASp-GFP-Aub ovarian extracts. Cbl mRNA was quantified using RT-qPCR. Normalization was with RpL32 mRNA. Mean of three biological replicates. The error bar represents standard error to the mean. * p-value <0.05 using the two-tailed Student's t test.",
    "ncbi_link": "Cbl: 38961
RpL32: 43573"
  },
  {
    "caption": "(G) ePAT assay of CblL mRNA. Ovaries from 1-day-old (germarium to stage 8) wild-type, aub and twin mutant females, and from 4- to 7-day-old bam mutant females were used.",
    "ncbi_link": "CblL: 38961"
  },
  {
    "caption": "(D, E) Coverage of CblL (D) and CblS (E) mRNAs with ovarian and embryonic piRNAs. Significant crosslink clusters are indicated in red at the top of the graphs.",
    "ncbi_link": "piRNAs: 
CblL: 38961"
  },
  {
    "caption": "(D, E) Coverage of CblL (D) and CblS (E) mRNAs with ovarian and embryonic piRNAs. Significant crosslink clusters are indicated in red at the top of the graphs.",
    "ncbi_link": "piRNAs: 
CblS: 38961"
  },
  {
    "caption": "(A-E) Cbl expression in germaria. (B-B'') Immunostaining of bamP-GFP germaria that express GFP under the bam promoter, with anti-GFP (green) and anti-Cbl 8C4 (red).",
    "ncbi_link": "bam: 43038"
  },
  {
    "caption": "Solubilized mitochondria from MITRAC12FLAG- or ACAD9FLAG-expressing cells were subjected to anti-FLAG immunoisolation and native elution. Eluates were analysed by 2D-BN/SDS-PAGE and western blot analysis. Total 0.8 % (MITRAC12FLAG isolation), 0.35 % (ACAD9FLAG isolation), Eluate 100 %.",
    "ncbi_link": "FLAG: 
ACAD9: 28976
MITRAC12: 28958"
  },
  {
    "caption": "Solubilized mitochondria from MITRAC15FLAG-expressing cells were first subjected to native anti-FLAG immunoisolation (Total 0.1 %, Eluate 10 %, lane 4). Purified complexes were applied to anti-MITRAC12 immunoisolation (Eluates 100 %, lane 5). All samples were analyzed by SDS-PAGE and immunoblotting.",
    "ncbi_link": "FLAG: 
MITRAC15: 55744"
  },
  {
    "caption": "Solubilized mitochondria from MITRAC15FLAG- or TIM21FLAG-expressing cells were subjected to anti-FLAG immunoisolation and analyzed by 2D-BN/SDS-PAGE and western blotting. MITRAC15FLAG isolation: Total 0.1 %, Eluate 100 %. TIM21FLAG isolation: Total 0.2 %, Eluate 66 % (TIM21FLAG decoration), 33 % (MITRAC15, ACAD9, MITRAC12, COX1 decoration).",
    "ncbi_link": "FLAG: 
MITRAC15: 55744
TIM21: 29090"
  },
  {
    "caption": "Solubilized mitochondria from MITRAC15FLAG- or C12ORF62FLAG- expressing cells were subjected to anti-FLAG immunoisolation and analyzed by SDS-PAGE and immunoblotting. Total 0.4 %, Eluate 100 % (MITRAC15FLAG isolation), 70 % (C12ORF62FLAG isolation).",
    "ncbi_link": "FLAG: 
MITRAC15: 55744
C12ORF62: 84987"
  },
  {
    "caption": "Solubilized mitochondria from ACAD9FLAG-or MITRAC15FLAG- expressing cells were subjected to anti-FLAG immunoisolation and analyzed by SDS-PAGE and immunoblotting. Total 0.5 % (ACAD9FLAG isolation), 0.4 % (MITRAC15FLAG isolation) Eluate 100 %. Asterisk (*) indicates TIM21 signal. ACAD9/ACAD9FLAG could not be separated with the used gel system, both proteins are detected with ACAD9 antiserum.",
    "ncbi_link": "FLAG: 
ACAD9: 28976
MITRAC15: 55744"
  },
  {
    "caption": "Mitochondria from wild type and MITRAC15-/- cells were isolated and subjected to steady-state protein analyses by western blotting.",
    "ncbi_link": "MITRAC15: 55744"
  },
  {
    "caption": "Mitochondria from wild type and MITRAC15-/- cells were isolated and analyzed by BN-PAGE. Triton X-100 (left site) or digitonin (right site) were used for solubilization. The amount of complex I was quantified utilizing the NDUFS1 signal and normalized against SDHA levels (error bars indicate SEM from three biological replicates).",
    "ncbi_link": "MITRAC15: 55744"
  },
  {
    "caption": "Complex I and citrate synthase activity were measured in WT and MITRAC15-/- cells (error bars indicate SEM from three biological replicates; *p < 0,05; unpaired t-test).",
    "ncbi_link": "MITRAC15: 55744"
  },
  {
    "caption": "Pulse-chase [35S]methionine radiolabeling of mitochondrial translation products in wild type and MITRAC15-/- cells. Samples were analyzed by SDS-PAGE and digital autoradiography. Signal intensity of ND2 was normalized to the ATP6 signal and the relative ND2 stability was calculated by relative chase ND2 signal/relative pulse ND2 signal (error bars indicate SEM from three biological replicates; *p < 0,05; unpaired t-test).",
    "ncbi_link": "MITRAC15: 55744"
  },
  {
    "caption": "Pulse radiolabeling after re-expressing MITRAC15FLAG in MITRAC15-/- cells. Samples were analyzed by SDS-PAGE and digital autoradiography. Relative pulse signal intensity of ND2 was normalized to ATP6 (error bars indicate SEM from three biological replicates; *p < 0,05; **p < 0.01; unpaired t-test).",
    "ncbi_link": "FLAG: 
MITRAC15: 55744"
  },
  {
    "caption": "Mitochondrial translation products were radiolabelled with [35S]methionine after siRNA-mediated depletion of ACAD9 in wild type and MITRAC15-/- cells. Cell lysates were analyzed by SDS-PAGE and digital autoradiography. For quantifications the signal intensity of ND2 was normalized to ATP6 and the relative ND2 stability was calculated by relative chase ND2 signal/relative pulse ND2 signal. (error bars indicate SEM from three biological replicates; *p < 0,05; **p < 0.01 ***p < 0.001; unpaired t-test).",
    "ncbi_link": "ACAD9: 28976
MITRAC15: 55744"
  },
  {
    "caption": "FLAG-immunoprecipitation was performed in mitochondrial extracts from MITRAC15FLAG-expressing cells after siRNA-mediated down regulation of ACAD9 and pulse radiolabeling. SDS-PAGE followed by autoradiography was used to analyze eluates. Relative signal intensity of ND2, ND3 and ND4L were normalized to ATP6 (total) or isolation efficiency (eluate). Total 2 %, Eluate 100 %. Error bars indicate SEM from three biological replicates; **p < 0.01; unpaired t-test.",
    "ncbi_link": "FLAG: 
ACAD9: 28976
MITRAC15: 55744"
  },
  {
    "caption": "After C12orf62 down regulation, [35S]methionine labelling was performed. During labeling mitochondrial translation was inhibited with puromycin (pur) (2 µg/ml). MITRAC15FLAG interacting nascent chains were isolated by FLAG-immunoprecipitation from cell lysates. Eluates were subjected to SDS-PAGE, analyzed by digital autoradiography. Total 2 %, MITRAC15FLAG eluates 100 % (in case of C12ORF62FLAG, 25% of eluate was loaded as a standard). Red asterisks, accumulating nascent chains of ND2. The accumulating nascent chains of ND2 of lane 12 is presented in a magnification. F1-F3 mark nascent chains of COX1 [18].",
    "ncbi_link": "FLAG: 
MITRAC15: 55744
C12orf62: 84987
C12ORF62: 84987"
  },
  {
    "caption": "Depletion of ACAD9 by siRNA was performed Total 1 %, Eluates 100 %. Red asterisks, accumulating nascent chains of ND2.",
    "ncbi_link": "ACAD9: 28976"
  },
  {
    "caption": "G IP of UbcH7 by  PknG or PknGΔUbl in U937  cells. Cells were  infected with WT, ΔpknG, or ΔpknG:pknGΔUbl Mtb strains as in B. H IP of UbcH7  by PknG or  PknG  E190A  in U937  cells. Cells were  infected with WT, ΔpknG, or ΔpknG:pknG E190A Mtb strains as in B. ",
    "ncbi_link": "pknG: 886397"
  },
  {
    "caption": "A  MS/MS analysis of UbcH7 in the absence (top) or presence (bottom) of PknG to reveal ubiquitination sites. Tryptic peptides spanning residues ranging from 74 to 100 were identified as the high-confidence peptides possessing  di-Gly modifications. The ubiquitinated residue (Lys82) in the peptide sequence is highlighted in red. The peak heights are the relative abundances of the corresponding fragmentation ions. Matched amino terminus-containing ions (b ions) are indicated in red, and matched carboxyl terminus-containing ions (y ions) are indicated in blue. Only the major peaks that were identified are labeled.",
    "ncbi_link": "PknG: 886397"
  },
  {
    "caption": "A Luciferase assay of NF-κB activation in HEK293T cells transfected with WT or mutant Mtb PknG. The graph shows the mean ± SEM of three independent biological replicates, n = 3. *P < 0.05, **P < 0.01. Data were analyzed according to one-way analysis of variance (ANOVA) using GraphPad Prism 7.",
    "ncbi_link": "PknG: 886397"
  },
  {
    "caption": "B IP of TRAF2 and TAK1 by  Mtb PknG  in U937 cells. Cells were infected with the indicated Mtb strains at an MOI of 1. Non-infected cells were used as controls. After 4 hours, the cells were lysed and  immunoprecipitated  with the antibody against PknG. The  immunoprecipitated  proteins were  immunoblotted with TRAF2, TAK1, TAB2 (negative control), or TAB3 (negative control) antibodies.",
    "ncbi_link": "PknG: 886397"
  },
  {
    "caption": "G, H In vivo ubiquitination assay of TRAF2 (G) and TAK1 (H) in the absence or presence of PknG in HEK293T cells transfected with the indicated plasmids for 24 hours. Cells were lysed and immunoprecipitated using the antibody against Flag. Immunoprecipitated proteins were immunoblotted with the antibody against HA.",
    "ncbi_link": "PknG: 886397"
  },
  {
    "caption": "A, B qPCR analysis of Tnf mRNA (A) and Il6 mRNA (B) in splenic cells from C57BL/6 mice infected with WT or mutant Mtb  stains for 0-20 days. Data are representative of one experiment with two independent biological replicates (mean ± SEM of n = 6 mice per group). *P < 0.05 and **P < 0.01. Data were analyzed according to one-way ANOVA using GraphPad Prism 7.",
    "ncbi_link": "Il6: 16193
Tnf: 21926"
  },
  {
    "caption": "The MR tail is the main contributor for Nek2A ubiquitination. Ubiquitination reactions performed with APC/CCdc20 for Nek2A wild type (Nek2AWT) and degron mutants. Nek2AK is the KEN box mutant (391KEN393/KAA), Nek2AK/D is the (KEN and D box mutant (391KEN393/KAA, 361RKFL364/AKFA), Nek2AMR is the 443∆MR mutant.",
    "ncbi_link": "Cdc20: 991
Nek2A: 4751"
  },
  {
    "caption": " The APC/C requires the Cdc20 coactivator subunit to ubiquitinate Nek2A. Nek2A ubiquitination reactions performed with the APC/C in absence and in presence of increasing concentrations of Cdc20 using the E2 UbcH10. ",
    "ncbi_link": "Nek2A: 4751"
  },
  {
    "caption": " Nek2A ubiquitination reactions performed with either APC/CCdc20 wild type (APC/CWT) or mutants. APC/C2m is the N392A/E395A mutant of Apc2. APC/C2/4m is the N392A/E395A/R48A/H53A/S51A mutant of Apc2 and Apc4. ",
    "ncbi_link": "Apc4: 29945
Apc2: 10297
Cdc20: 991"
  },
  {
    "caption": " Securin ubiquitination reactions performed with either APC/CCdc20 wild type (APC/CWT) or mutants. ",
    "ncbi_link": "Cdc20: 991"
  },
  {
    "caption": "Ubiquitination reactions of either Nek2A or securin by the APC/CCdc20 and the effect of increasing concentrations of the MCC.",
    "ncbi_link": "Cdc20: 991
Nek2A: 4751
securin: 9232"
  },
  {
    "caption": "Size exclusion chromatography peak fractions of APC/C complexes with Nek2A APC/CΔApc15 is the Apc15 deleted mutant APC/C,",
    "ncbi_link": "Apc15: 25906"
  },
  {
    "caption": " Size exclusion chromatography peak fractions of APC/C complexes with Nek2A APC/CΔApc15 is the Apc15 deleted mutant APC/C, ",
    "ncbi_link": "Apc15: 25906"
  },
  {
    "caption": " Size exclusion chromatography peak fractions of APC/C complexes with Nek2A MCCΔIR is the Cdc20 IR tail deleted mutant MCC. MCC-BubR1Wm is the MCC mutant at the APC2WHB binding surface on BubR1 ",
    "ncbi_link": "BubR1: 701
Cdc20: 991"
  },
  {
    "caption": " Size exclusion chromatography peak fractions of APC/C complexes securin MCC-BubR1Wm is the MCC mutant at the APC2WHB binding surface on BubR1 ",
    "ncbi_link": "BubR1: 701"
  },
  {
    "caption": "Ubiquitination reactions of cyclin A by the APC/CCdc20 in presence of increasing concentrations of either UbcH10 or UbcH5.",
    "ncbi_link": "Cdc20: 991"
  },
  {
    "caption": " Ubiquitination reactions of Nek2A by the APC/CCdc20 in presence of increasing concentrations of either UbcH10 or UbcH5. ",
    "ncbi_link": "Cdc20: 991"
  },
  {
    "caption": " Exemplary still images from time courses between NEBD and anaphase of eGFP-Nek2A degradation in HEK cells. Cells were either treated with siGL2 as control or depleted of the indicated E2 enzymes. The chromosomes are coloured in cyan and eGFP-Nek2A in green, with the outline of the cells are indicated with dashed yellow lines. Time is given as hh:mm. Scale bar 10 μm. ",
    "ncbi_link": "eGFP: 
GL2: 844323
Nek2A: 4751"
  },
  {
    "caption": " Degradation profiles of eGFP-cyclin A2 (top) and eGFP-Nek2A (bottom) in HEK cells during mitosis. The timepoint of NEBD is marked at 0 minutes in the graphs. Asterisks indicate values that are significantly different from the same time point of the siGL2 control as determined by a Mann-Whitney U-test Mean ± s.d. is shown. The number of cells analysed are N = 66 (Cyclin A2 siGL2), 52 (Cyclin A2 siUbcH5), 28 (Cyclin A2 siUbcH10), 27 (Cyclin A2 siU5/siU10), 80 (Nek2A siGL2), 64 (Nek2A siUbcH5), 21 (Nek2A siUbcH10), 32 (Nek2A siU5/siU10). All data are from at least two biological replicates. ",
    "ncbi_link": "GL2: 844323
UbcH10: 11065
UbcH5: 7321"
  },
  {
    "caption": "(D) Analysis and quantification of a time dependent increase of ARSA activity in MSD primary fibroblasts (variant FGE Gly247Arg homozygous) simultaneously treated with 10 and 20 µM tazarotene and bexarotene, respectively, up to 21 days. Data represent mean ±SD of 3-6 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent treatment times. #### p<0.0001. Difference against 0 days control: * p<0.05, **** p<0.0001.",
    "ncbi_link": "FGE: 285362"
  },
  {
    "caption": "(E) Analysis and quantification of increased sulfatase activities different to ARSA, namely ARSB, GALNS, and STS in MSD primary fibroblasts (variant FGE Gly247Arg homozygous) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM. Data represent mean ±SD of 3-6 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. *** p<0.001, **** p<0.0001.",
    "ncbi_link": "FGE: 285362"
  },
  {
    "caption": "(F) Quantification of ARSA activities in MSD primary fibroblasts with different homozygous SUMF1 mutations (FGE Gly247Arg, FGE Gly263Val, FGE Ala279Val, FGE Arg349Trp) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. ****p<0.0001.",
    "ncbi_link": "SUMF1: 285362
FGE: 285362"
  },
  {
    "caption": "(A) ARSA protein amount quantification after treatment of MSD primary fibroblasts (variant FGE Gly247Arg homozygous) with tazarotene, bexarotene, and tazarotene/bexarotene in combination for 6 days referred to β- actin amounts and normalization of ARSA activity based on ARSA protein amount (specific ARSA activity). Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent concentrations. # p<0.05. Difference against 0/0 µM control: * p<0.05, *** p<0.001.",
    "ncbi_link": "FGE: 285362"
  },
  {
    "caption": "(C) Quantification of ARSA activities in CRISPR/Cas9 generated ARPE19 SUMF1 -/- cells and appropriate controls (ARPE19 wild type, MSD primary fibroblasts (variant FGE Gly247Arg homozygous)) after 6 days of simultaneous treatment with tazarotene/bexarotene 10/20 µM for up to 21 days. Data represent mean ±SD of 3 independent experiments (biological replicates). One-way ANOVA followed by Tukey's test for multiple comparisons. Displayed are significance levels for the next significant difference between adjacent concentrations. ## p<0.01. Difference against 0 days control: **** p<0.0001.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
FGE: 285362
SUMF1: 285362"
  },
  {
    "caption": "(B) MiSeq analysis of the indicated gene targeting approaches from samples collected at the indicated time points post editing. DPP9 and DPP8 were targeted with one gRNA/target gene, CARD8 was targeted with two gRNAs. On the day of nucleofection, T cells were activated with human T activator CD3/CD28 beads and expanded in the presence of IL-2. On day 10, cells were switched to IL-7/IL-15 containing medium. (C) Fraction of wildtype and in-frame reads are depicted. One representative experiment out of three is shown. ",
    "ncbi_link": "CARD8: 22900
DPP8: 54878
DPP9: 91039"
  },
  {
    "caption": "(C) Northern blot validation of SpoY, SpoX  and nc037 expression  in  early exponential (EE), mid-exponential  (ME), early late exponential (eLE), late exponential  (LE),  early stationary (eST) and stationary  (ST) phase of growth in TY medium. 5S rRNA served as a loading ctl. A representative image of three independent experiments is shown.",
    "ncbi_link": "5S rRNA: 
nc037: 
SpoX: 
SpoY: "
  },
  {
    "caption": "(A) Quantification of EMSAs  (error bars represent the mean ± SD of n=3 biological replicates performed with either  32P-labeled SpoY  or SpoX  (short isoform) with increasing concentrations of the spo0A  target region, respectively. Purified Hfq  was added to facilitate SpoY-spo0A  complex formation. Mutating the respective sRNA seed region (Appendix Figure S4A, SpoY*/SpoX*) abolished the interaction, while introducing compensatory mutations into the spo0A  target region (spo0A*C) slightly rescued the complex formation.",
    "ncbi_link": "SpoX: 
SpoY: 
spo0A: 66353625"
  },
  {
    "caption": "(B) In-line probing of 0.2 pmol of 32P-labeled SpoY  and SpoX  (short isoform) in the absence (lane 4) or presence of increasing concentrations (lane 5-7) of the spo0A  long 5′UTR (starting from pTSS) and first 69 nt of the CDS. RNase T1  and alkali-digested (OH) SpoY  and SpoX  serve as ladders respectively. Secondary structure and predicted seed region are highlighted. A representative image of three independent experiments is shown.",
    "ncbi_link": "SpoX: 
SpoY: 
spo0A: 66353625"
  },
  {
    "caption": "(C) mCherry  fluorescence of translational fusion constructs (error bars represent the mean ± SD of n=5 biological replicates, expressed in the respective sRNA knock-out background. Fluorescence intensity was normalized to that of the respective p[spo0A] ctl. Mutating the sRNA seed regions (Appendix Figure S4A, SpoY*/SpoX*) abolished the impact on spo0A translation, while introducing compensatory mutations into the spo0A  target region (spo0A*C) partially rescued the effect. The long SpoX   isoform used in reporter assays. Ordinary one-way ANOVA with Dunnett′s multiple comparison test was used to calculate statistical significance. Not significant (ns) P > 0.05; (∗) P ≤ 0.05; (∗∗∗∗) P ≤ 0.0001.",
    "ncbi_link": "mCherry: 
SpoX: 
SpoY: 
spo0A: 66353625"
  },
  {
    "caption": "(A) Western blot  analysis comparing Spo0A  protein levels in a WT strain (p[ctl]), sRNA knock-out mutants (ΔSpoY/ΔSpoX-p[ctl]) and strains constitutively expressing the respective sRNA (ΔSpoY/ΔSpoX-p[ΔSpoY/ΔSpoX]). Equal optical density (OD) units of total cell lysates (error bars represent the mean ± SD of n=3 biological replicates) were loaded from strains gown till mid-exponential  (ME) or stationary  (ST) phase of growth in TY. Band intensities were measured and Log2 fold changes were calculated relative to the respective WT. Western blot  membranes were incubated with anti-Spo0A  antibody. To calculate statistical significance, an ordinary one-way ANOVA with Dunnett′s multiple comparison test was applied in. Not significant (ns) P > 0.05; (∗) P ≤ 0.05; (∗∗∗) P ≤ 0.001. For western blot  analysis Ponceau S staining  of the blotting  membrane served as loading control",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "Transcript levels of genes encoding sporulation-specific sigma factors and their respective regulon in sRNA knock-out mutants (ΔSpoY/ΔSpoX-p[ctl]) and strains constitutively expressing the respective sRNA (ΔSpoY/ΔSpoX-p[ΔSpoY/ΔSpoX]) relative to  C. difficile 630  WT (p[ctl]). A schematic representation of the first four stages of sporulation in  C. difficile is given on the left. RNA was extracted from samples (n = 3 biological replicates) taken at 9 h and 12 h post induction of sporulation on 70:30 sporulation plates. Log2 fold changes were calculated relative to the WT. Statistical significance was determined using two-way ANOVA with Dunnett′s multiple comparison test. P > 0.05; (∗) P ≤ 0.05; (∗∗) P ≤ 0.01; (∗∗∗) P ≤ 0.001; (∗∗∗∗) P ≤ 0.0001. Error bars represent the mean ± SD.",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "(A) Representative phase-contrast images (n=4) of a WT strain (p[ctl]), sRNA knock-out mutants (ΔSpoY/ΔSpoX-p[ctl]) and strains constitutively expressing the respective sRNA (ΔSpoY/ΔSpoX-p[ΔSpoY/ΔSpoX]) at 6 h, 12 h, 24 h and 48 h post inoculation of 70:30 liquid sporulation medium. (B)  Sporulation frequencies  calculated based on  phase-contrast microscopy. Error bars represent the mean ± SD of n=4 biological replicates (A). 2-way ANOVA with Dunnett′s multiple comparison test was used to calculate statistical significance. Not significant (ns) P > 0.05; (∗∗) P ≤ 0.01; (∗∗∗) P ≤ 0.001; (∗∗∗∗) P ≤ 0.0001.",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "(B)  Body weight loss over the course of 7 days (data points and error bars represent mean ± standard error of the mean; the dotted lines serve as a visual guideline) of mice  infected with  C. difficile 630 WT (n=15), ΔSpoY (n=15) or ΔSpoX (n=15)are indicated",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "(C) final colon  length at day 7 post infection of uninfected mice  (n=10) and mice  infected with C. difficile 630 WT (n=15), ΔSpoY (n=15) or ΔSpoX (n=15)are indicated (box-and-whisker plots show minimum, first quartile, median, third quartile, and maximum). Data information: Kruskal-Wallis was performed with Dunnett′s multiple comparison test to calculate statistical significance in (C) Not significant (ns) P > 0.05; (∗) P ≤ 0.05; (∗∗) P ≤ 0.01; (∗∗∗) P ≤ 0.001; (∗∗∗∗) P ≤ 0.0001.",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "(D) Comparison of CFUs  of C. difficile vegetative cells  and spores   in fecal  pellets of mice  at different time points  during infection  with  C. difficile 630 WT (n=15), ΔSpoY (n=15) or ΔSpoX  (n=15). Replicates with CFUs  below the detection limit were set to 100. Box-and-whisker plots show minimum, first quartile, median, third quartile, and maximum. Data information: Kruskal-Wallis was performed with Dunnett′s multiple comparison test to calculate statistical significance in (D). Not significant (ns) P > 0.05; (∗) P ≤ 0.05; (∗∗) P ≤ 0.01; (∗∗∗) P ≤ 0.001; (∗∗∗∗) P ≤ 0.0001.",
    "ncbi_link": "SpoX: 
SpoY: "
  },
  {
    "caption": "Immunoblot from immunoprecipitation (IP) assays to validate the predicted model of UFL1/UFBP1 interaction in cells. UFL1WT-3xFLAG and UFL1L45R-3xFLAG were transiently overexpressed along with UFBP1-SBP in HEK293T-UFL1 KO cells and subjected to separate pulldowns using anti-FLAG antibody or streptavidin. Immunoprecipitated material was run on a 4-12% SDS PAGE gel and analysed by immunoblotting using indicated antibodies.",
    "ncbi_link": "3xFLAG: 
UFBP1: 65992
UFL1: 23376"
  },
  {
    "caption": "D. (Top) Relative enrichment of the three microRNAs across different cell types. Quantitative expression of microRNAs in primary hippocampal neurons, primary astrocytes and primary microglia. miR-146a-5p is significantly enriched in microglia, while miR-148a-3p and miR-181a-5p are significantly enriched in neurons. N = 5/group, Two-way ANOVA, Tukey's multiple comparisons test, *P<0.05, **P<0.01. Bars and error bar indicates mean ± sem. (Bottom) miRNA expression in different cell types of mouse brain stem. The data was retrieved from Hoye et al. 2017.",
    "ncbi_link": "miR-146a-5p: 387164
miR-148a-3p: 387166
miR-181a-5p: 387176"
  },
  {
    "caption": "E. Overexpression of microRNAs in relevant cell types for 48 hours followed by genome wide RNA-seq analysis. miR-181a-5p was overexpressed in primary hippocampal neurons, while miR-146a-5p was overexpressed in microglia culture. Immortalized microglial cell line was used for this purpose. Given that miR-148a-3p was highly enriched in neurons (D), primary hippocampal neurons were treated with the corresponding miR-148a-3p mimic. PCA plot shows that the mimic and control treated samples cluster distinguishingly separate from one another. Volcano plot displays the genes significantly deregulated in mimic treated samples compared to control samples (FDR <0.05). Red color indicates the up-regulated genes while the blue color represents the genes those were down-regulated.",
    "ncbi_link": "miR-146a-5p: 387164
miR-148a-3p: 387166
miR-181a-5p: 387176"
  },
  {
    "caption": "H. qPCR analysis confirms the over-expression of pro-inflammation related genes (IL-1ß, IL-6, TNF-alpha) due to overexpression of miR-146a-5p. Expression of anti-inflammatory gene, IL-10 was downregulated in mimic treated cells compared to the controls. Unpaired t-tests, two-tailed, ****P<0.0001, ***P<0.001, **P<0.01, *P<0.05. Bars and error bar indicates mean ± sem. Number of biological replicates: 5-6/group.",
    "ncbi_link": "IL-10: 16153
IL-1ß: 16176
IL-6: 16193
miR-146a-5p: 387164
TNF-alpha: 21926"
  },
  {
    "caption": "H. Escape latency during the water maze training comparing 7 months old wild type mice (WT-control, n = 17, male: 9, female: 8) and APPPS-21 mice (APP-control, n = 8, male: 6, female: 2) injected with scramble control oligonucleotides and APPPS1-21 mice injected with microRNA inhibitors (APP miR-inhibtor mix, n = 12, male: 8, female: 4). Bars and error bars indicate mean ± sem..",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "D. qPCR assay for several synaptic genes (LRKK2, Cadm3 and Slc6a11) confirms reinstatement of gene expression with anti-miR-mix (n = 5-7, Kruskal-wallis test).",
    "ncbi_link": "Cadm3: 94332
LRKK2: 66725
Slc6a11: 243616"
  },
  {
    "caption": "G. qPCR data shows rescue of AFF2/FMR2 and Hivep3 expression in APP/PS1 mice treated with inhibitor cocktail (n = 6-7, Kruskal-wallis test).",
    "ncbi_link": "AFF2: 14266
FMR2: 14266
APP: 351
Hivep3: 16656
PS1: 5663"
  },
  {
    "caption": "A Skeletal muscles in the lower legs were dissected and RNA was extracted on postnatal day 0, 7, and 21. The expression of R3hdml was examined by RT-PCR. GAPDH was used as an internal control. MM, 100 bp DNA marker. B Quantification of RT-PCR results. Data are expressed as the means ± standard error of the mean (SEM). The experiments were repeated at least three times. **** p < 0.0001 vs. day 0 group; one-way ANOVA followed by Bonferroni post-hoc test.",
    "ncbi_link": "GAPDH: 
R3hdml: 100043899"
  },
  {
    "caption": "A Cultured C2C12 cells were transfected with the firefly luciferase construct containing the 781 bp fragment upstream of the translational start codon of the R3hdml coding sequence (R3hdml-luc), together with Renilla luciferase vectors as controls; the cells were then differentiated in the presence of 2% horse serum. Cells were harvested at the indicated time points, after which luciferase activity of the cell lysate was measured.",
    "ncbi_link": "luc: 
luciferase: 
R3hdml: 100043899"
  },
  {
    "caption": "C Plasmids containing MyoD cDNA or empty vector were transfected into C2C12 cells. One day and 3 days after transfection, cells were lysed and subjected to SDS-PAGE and western blotting using anti-MyoD antibodies.",
    "ncbi_link": "MyoD: 17927"
  },
  {
    "caption": "D Plasmids containing MyoD cDNA or empty vector together with R3hdml-luc and Renilla luciferase vectors were transfected into C2C12 cells. One day and 3 days after transfection, the luciferase activity of the cell lysate with or without MyoD overexpression was measured. Relative luciferase activity is expressed as the fold activity above the background conferred by the empty vector together with R3hdml-luc.",
    "ncbi_link": "luc: 
luciferase: 
MyoD: 17927
R3hdml: 100043899"
  },
  {
    "caption": "A R3hdml siRNA or non-targeting siRNA was transfected into C2C12 cells. Then, C2C12 cells were differentiated into myotubes. RNA was extracted from the cells after induction of differentiation at the indicated time points. Closed bars, control; open bars, silenced R3hdml gene; ** p < 0.01; * p < 0.05; Student's t-test.",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "A Satellite cells were isolated by enzymatic digestion from R3hdml KO (n = 6) and wild type control (n = 6) mice and placed in culture medium. Then, cell proliferation was evaluated by Ki67 staining. Cell nuclei were stained with DAPI. B The ratio of Ki67 positive cells to total cells (DAPI-positive) was evaluated. The number of cells was counted under approximately 60 fields of view for each well. Closed columns, wild type controls; open columns, R3hdml KO mice. * p < 0.05; Student's t-test. ",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "Thirty freshly isolated myofibers from 8-12-week-old R3hdml KO (n = 7) and wild type mice (n = 7) were cultured for 72 h. Then, the isolated myofibers were fixed with 4% PFA followed by immunostaining using anti Pax-7, anti MyoD, and anti Myog antibodies. (C, D) Co-immunostaining parallel cultures for Pax7 and MyoD showed that there were fewer cells with the self-renewing Pax7+/MyoD− phenotype in muscles from R3hdml KO mice compared with control; Pax7+/MyoD− cells (arrowheads), Pax7−/MyoD+ cells (yellow arrows) and Pax7+/MyoD+ cells (white arrows). * p < 0.05; Student's t-test.",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "(E, F) Co-immunostaining parallel cultures for MyoD and Myog showed that there were fewer cells with the differentiating MyoD−/Myog+ phenotype in muscles from R3hdml KO mice compared to control; MyoD−/Myog+ cells (arrowheads), MyoD-/Myog+ cells (yellow arrows), and MyoD+/Myog+ cells (white arrows). * p < 0.05; Student's t-test.",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "A Seven days after CTX injection, skeletal muscles were dissected, fixed, and embedded in paraffin. Two consecutive sections were utilized, and the first section was subjected to in situ hybridization using an R3hdml sequence-specific RNA probe to detect Rh3dml, while the second section was used for IHC using the anti-MyoD antibody. MyoD protein was visualized with DAB stain (brown). R3hdml expression is highly detected in MyoD-positive cells. Scale bar in low magnification images = 100 µm; in high magnification images = 25µm.",
    "ncbi_link": "R3hdml: 100043899
Rh3dml: 100043899"
  },
  {
    "caption": "B One hundred microliters of 10 µM CTX was intramuscularly injected into the forearm muscle of anesthetized R3hdml KO ([b], n = 10) and wild type control ([a], n = 10) mice. Subsequently, hand grip was evaluated 0, 3, 6, and 14 days after CTX injection. R3hdml genes were overexpressed in the forearm muscle of anesthetized R3hdml KO mice ([c], n = 10) and hand grip was also evaluated 0, 3, 6, and 14 days after CTX injection. Data are expressed as the means ± standard error of the mean (SEM). ** p < 0.01; **** p < 0.0001 vs. wild type control; # p < 0.05; ## p < 0.01 vs. R3hdml KO mice; two-way ANOVA followed by a Bonferroni post hoc comparison of the individual time points.",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "C Myofibers were freshly dissected from 8-12-week-old R3hdml KO (n = 4) and control mice (n = 4) 35 days after CTX injection, and the number of satellite cells was evaluated by Pax-7 staining. Arrowheads indicate Pax-7-positive cells. The number of Pax-7-positive cells per myofiber was counted. At least 50 myofibers in each animal were evaluated. Closed columns, wild type controls; open columns, R3hdml KO mice. Data are expressed as the means ± standard error of the mean (SEM). * p < 0.05; Student's t-test.",
    "ncbi_link": "R3hdml: 100043899"
  },
  {
    "caption": "B Expression levels of GlcNAc in wild-type (WT) GAS, ΔgacG, H, I, J, K, and L were measured as the sWGA fluorescence intensity (normalized to WT GAS).",
    "ncbi_link": "gacG: "
  },
  {
    "caption": "B, C Accumulation of LC3-II. (B) Representative western blot of LC3-II during non-infection (NI), WT GAS, ΔgacI, and ΔgacI::gacI. (C) LC3-II intensity normalized to NI.",
    "ncbi_link": "gacI: "
  },
  {
    "caption": "D, E Recruitment of ubiquitin in GAS-infected cells. HeLa cells were infected with WT GAS, ΔgacI, and ΔgacI::gacI for 4 h, fixed, and immunostained for ubiquitin (FK2: magenta). Cellular and bacterial DNA were stained with DAPI (cyan). (D) Representative confocal images and (E) percentage of cells with ubiquitin-positive GAS. Scale bar, 10 μm.",
    "ncbi_link": "gacI: "
  },
  {
    "caption": "I, J Recruitment of p62 to gacI mutants. HeLa cells were infected with WT GAS, ΔgacI, and ΔgacI::gacI for 4 h, fixed, and immunostained for p62 (magenta). Cellular and bacterial DNA were stained with DAPI (cyan). (I) Representative confocal images and (J) percentage of cells with p62-positive GAS. Scale bar, 10 μm.",
    "ncbi_link": "gacI: "
  },
  {
    "caption": "E, F Localization of EmGFP-FBXO2 in GAS-infected cells. HeLa cells transfected with GFP-FBXO2 (green) were infected with the indicated GAS strains for 2 or 4 h at an MOI of 100; scale bar, 10 μm. Representative confocal images at 4 h of WT GAS, ΔgacI, and ΔgacI::gacI (E) and (F) percentages of FBXO2‐positive cells.",
    "ncbi_link": "gacI: "
  },
  {
    "caption": "B, HeLa cells transfected the indicated GFP-FBXO2 mutants (green) were infected with WT GAS for 4 h; scale bar, 10 μm. Representative confocal images (B)",
    "ncbi_link": "GFP: 
FBXO2: 26232"
  },
  {
    "caption": "E, F Recruitment of FBXO2 to intracellular GAS in SKP1/CUL1/ROC1 knockdown cells. HeLa cells transfected with GFP-FBXO2 (green) and the indicated siRNAs were infected with GAS, fixed at 4 h; scale bar, 10 μm. Representative confocal images (E) and percentages of FBXO2 localized to GAS (F).",
    "ncbi_link": "CUL1: 8454
ROC1: 6016
SKP1: 6500"
  },
  {
    "caption": "D HeLa WT or FBXO2-KO cells transfected with mCherry-Gal3 (magenta) were infected with WT GAS for 2 or 4 h, and percentages of Gal3-positive GAS-containing cells were quantified.",
    "ncbi_link": "FBXO2: 26232"
  },
  {
    "caption": "E - J Localization of ubiquitin, LC3 and p62 in FBXO2 KO cells. HeLa WT or FBXO2-KO cells were infected with WT GAS for 4 h, fixed, and immunostained for ubiquitin (FK2: magenta) or LC3 (magenta) or p62 (magenta). Representative confocal images (E, G, and I) and percentages of cells with ubiquitin, LC3, or p62 -positive GAS (F, H, and J).",
    "ncbi_link": "FBXO2: 26232"
  },
  {
    "caption": "M, N GlcNAc recognition of FBXO2 required for GAS xenophagy. Non-transfected HeLa WT cells and HeLa FBXO2-KO cells transfected GFP, GFP-FBXO2, GFP-FBXO2 YW/AA were infected with GAS WT for 4 h, fixed, and immunostained for ubiquitin. Percentages of cells with LC3 (M) or ubiquitin (N) -positive GAS were quantified.",
    "ncbi_link": "FBXO2: 26232"
  },
  {
    "caption": "A-C Recruitment of LC3 and ubiquitin to intracellular GAS in SKP1/CUL1/ROC1 knockdown cells. HeLa cells transfected with mCherry-LC3 (magenta) and the indicated siRNAs were infected with GAS for 4 h. Cells were immunostained for ubiquitin (FK2); scale bar, 10 μm. Representative confocal images (A) and percentages of cells with ubiquitin (B) and LC3 (C) -positive GAS.",
    "ncbi_link": "CUL1: 8454
ROC1: 6016
SKP1: 6500"
  },
  {
    "caption": "H. Representative confocal images of IBA-1-stained mononuclear phagocytes on choroidal flat mounts from LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D7 and D14. Examples of macrophage quantification (yellow stars) are presented in side panels. Scale bar: 20μm. I, J. Total number of IBA-1-positive mononuclear phagocytes counted around laser impact area on confocal images of choroidal flat mounts at D7 (I) and D14 (J); n = 19 burns (D7 LysM-Cre/Nrp1+/+), n = 25 burns (D7 LysM-Cre/Nrp1fl/fl) n = 37 burns (D7 LysM-Cre/Nrp1+/+), n = 23 burns (D7 LysM-Cre/Nrp1fl/fl), 3-5 mice with ~4 burns per eye.",
    "ncbi_link": "Cre: 2777477
LysM: 4069
Nrp1: 8829"
  },
  {
    "caption": "K. Compilation of representative compressed Z-stack confocal images of FITC-dextran-labeled CNV and IB4-stained laser impact area from LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D14. Scale bar: 20μm. L-N. Quantification of area of FITC-dextran-labeled CNV (L), isolectin B4 (IB4 )-stained laser impact area (M) and the ratio of FITC/IB4 per laser-burn (N) relative to LysM-Cre/Nrp1+/+ at D14; n = 23 burns (LysM-Cre/Nrp1+/+), n = 27 burns ( LysM-Cre/Nrp1fl/fl).",
    "ncbi_link": "Cre: 2777477
LysM: 4069
Nrp1: 8829"
  },
  {
    "caption": "A-D. mRNA expression of inflammation markers relative to LysM-Cre/Nrp1+/+ in mouse RPE-choroid-sclera complexes at D3 for Il1b (A); n = 10 (LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl), Il6 (B); n = 7 (LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl), Vegfa (C); n = 10 (LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl), Tnf (D); n = 5 (LysM-Cre/Nrp1+/+), n = 10 (LysM-Cre/Nrp1fl/fl).",
    "ncbi_link": "Cre: 2777477
Il1b: 3553
Il6: 3569
LysM: 4069
Nrp1: 8829
Tnf: 7124
Vegfa: 7422"
  },
  {
    "caption": "K, L. mRNA expression relative to LysM-Cre/Nrp1+/+ of inflammation markers in mouse BMDMs for Il1b (K); n = 4 (LysM-Cre/Nrp1+/+), n = 5 (LysM-Cre/Nrp1fl/fl) and Il6 (L); n = 3 (LysM-Cre/Nrp1+/+), n = 2 (LysM-Cre/Nrp1fl/fl)",
    "ncbi_link": "Cre: 2777477
Il1b: 16176
Il6: 16193
LysM: 4069
Nrp1: 8829"
  },
  {
    "caption": "P. Heatmap (left) and enrichment plot (right) of GO Angiogenesis gene set enrichment analysis (GSEA) of wildtype and LysM-Cre/Nrp1fl/fl peritoneal macrophages; n = 2. NES, normalized enrichment score; FDR, false discovery rate.",
    "ncbi_link": "Cre: 2777477
LysMbutton type=\"button\" class=\"btn btn-success btn-xs\" ng-click=\"confirmPretag()\" ng-show=\"!showA: 4069
Nrp1: 8829"
  },
  {
    "caption": "J-L. Quantification of area of FITC-dextran-labeled CNV (J), isolectin B4 (IB4)-stained laser impact area (K) and the ratio of FITC/IB4 per laser-burn (L) relative to LysM-Cre/Nrp1+/+ + Vehicle in Vehicle and NRP1-derived trap treated LysM-Cre/Nrp1+/+ and LysM-Cre/Nrp1fl/fl mice at D14; n = 16 burns (LysM-Cre/Nrp1+/+ + Vehicle), n = 16 burns (LysM-Cre/Nrp1+/+ + Trap), n = 13 burns (LysM-null/Nrp1fl/fl + Vehicle) , n = 19 burns (LysM-Cre/Nrp1fl/fl + Trap).",
    "ncbi_link": "Cre: 2777477
LysM: 4069
Nrp1: 8829"
  },
  {
    "caption": "(C) Representative images of P90 SC cross sections of SOD1G93A and WT mice. Red: denotes  NeuN, Green: denotes CRMP4. Scale bar: 10 μm. (D) Quantification of the percentage of CRMP4 positive SC neurons in 3 WT VS. 3 SOD1G93A mice. We monitored CRMP4 expression in total of 108 cells in WT condition and 123 cells in  SOD1G93A, an average of 36 or 41 cells in each repeat respectively. Student's t-test, n = 3, Data presented as mean ±SE, *p = 0.0161. ",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(C) Representative images of SOD1G93A/ChAT::tdTomato  or WTChAT::tdTomato neuromuscular junctions at P90. White: denotes  BTX, Red: denotes direct ChAT, Green: denotes CRMP4, Yellow: denotes Z projection of 3D Imaris  co-localization of CRMP4 and ChAT. Scale bar: 10 µm. (D) Quantification of CRMP4 positive NMJs in gastrocnemius muscles from 3 WT or 3 SOD1G93A P90  mice. Total of 44 NMJ's in WT condition and 60 NMJ's in  SOD1G93A condition. Student's t-test, n=3, Data presented as mean ±SE, *p = 0.0157. (E) Quantification of the percent of partially denervated  NMJ's  in the presence or absence of CRMP4 immunostaining  in 3 different SOD1G93A mice. We counted 24 NMJ's in SOD1G93A CRMP4 negatives and 67 NMJ's in SOD1G93A CRMP4  positives. Student's t-test, n=3, Data presented as mean ±SE, *p = 0.0352. ",
    "ncbi_link": "tdTomato: 
ChAT: 12647
SOD1: 6647"
  },
  {
    "caption": "(F) Representative  images  of P90  SOD1G93A and WT sciatic nerves. Red: denotes  NFH, Blue: denotes  GFAP  and green denotes CRMP4, Yellow: denotes the Z projection of 3D Imaris co-localization of CRMP4  and NFH. Scale bar: 5 μm. (G) Quantification of the co-localization  area of CRMP4 with NFH in the sciatic nerve in 3 SOD1G93A mice compared to 3 WT mice using Imaris analysis. 14 WT sciatic nerve sections and 11 SOD1G93A sections were monitored. Data presented as mean ±SE. Student's t-test, n=3, ****p<0.0001. ",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(A) Representative images of healthy or C9orf72 iPSC-derived  MNs treated with Sema3A  or untreated in the distal compartment, 6 hours post treatment. Red: denotes Tubulin, Green: denotes CRMP4. Scale bar: 5 μm. (B) Quantification of CRMP4 intensity levels in healthy or C9orf72 iPSC-derived MNs with Sema3A treatment or untreated. 14 untreated healthy axons, 12 healthy axons with Sema3A treatment, 49 untreated C9orf72 axons  and 31 C9orf72 axons with Sema3A treatment were monitored from 3 different chambers. One-way ANOVA, Tukey's multiple comparisons test, n = 3, Data presented as mean ±SE, *p = 0.0338; ****p<0.0001. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(D) Representative images  of healthy or C9orf72 human-derived MN cell somata with Sema3A  treatment, Sema3A + dynein inhibitor treatment, or untreated. Gray: denotes CTX, Green: denotes CRMP4. Scale bar: 5μm. (E) Quantification of  CRMP4 intensity (normalized to GAPDH+mCherry/area) levels at the somata of healthy or C9orf72 human-derived MN  after Sema3A  treatment, Sema3A + dynein inhibitor treatment, or untreated. Analysis performed in 3 independent chambers per condition. 19 healthy untreated cell somata, 26 healthy cell somata with Sema3A treatment, 20 healthy cell somata with Sema3A  + dynein  inhibitor treatment and 14 C9orf72 cell somata from each condition were monitored. One-way ANOVA, Newman-Keuls multiple comparisons test, n=3, Data presented as mean ±SE, *p=0.0207; ***p=0.0004. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(F) Representative images of healthy or C9orf72 human-derived MN proximal axons with Sema3A treatment, Sema3A + dynein inhibitor treatment or untreated control. Green: denotes CRMP4, Red: denotes GAPDH. Scale bar: 5μm. (G) Quantification of CRMP4 intensity levels (normalized to GAPDH+mCherry/area) at the proximal axons in healthy or C9orf72 human-derived MN after Sema3A treatment, Sema3A + dynein  inhibitor treatment, or untreated control. Analysis performed from 3 independent chambers in each condition. 21 healthy untreated proximal axons, 24 healthy proximal  axons  with Sema3A treatment, 16 healthy proximal  axons with Sema3A + dynein inhibitor treatment, 12 C9orf72  untreated proximal axons, 8 C9orf72 proximal axons with  Sema3A treatment and 13 C9orf72 proximal axons with Sema3A +  dynein  inhibitor treatment were monitored. One-way ANOVA, Newman-Keuls multiple comparisons test, n = 3, Data presented as mean ±SE, *p =0.0334, ****p<0.0001. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(F) Upper panel - Immunoprecipitation assay with anti‐Flag antibody followed by Western blot analysis of dynactin (p150) in COS7  cells overexpressing Flag-CRMP4 (size of ~65 KDa). Lower panel - Total input (size of ~150 KDa). (G) Quantification of the blot in F. The dynactin intensity  band was normalized to the Flag-CRMP4 intensity band in each repeat. Student's t-test, n=3, Data presented as mean ±SE, *p=0.0299. ",
    "ncbi_link": "Flag: 
CRMP4: 22240"
  },
  {
    "caption": "(H)  Immunoprecipitation of  DIC (size of ~75 KDa) followed by Western blot analysis of CRMP4  (size of ~64 KDa) in COS7 cells that were transfected with CRMP4 and AAV9-50aa or its control.  IgG antibody was used as a control. (I) Quantification of the blot  in H from 3 independent repeats. The CRMP4 intensity  band was normalized to the DIC intensity band in each repeat. Student's t-test, n=3, Data presented as mean ±SE, *p=0.0479. ",
    "ncbi_link": "CRMP4: 22240"
  },
  {
    "caption": "(E) Representative images from the proximity ligation assay (For explanation of  PLA  technique; please refer to method section) for CRMP4 and dynein in   SODG93A and WT primary  MNs axons that were exposed to either control or Sema3A 8h post treatment. Scale bar: 5µm. (F) Quantification of the  CRMP4-DIC puncta number per primary  motor neuron axon in each condition. We analyzed ~20 axons per condition from 3 independent chambers per group (One-way ANOVA, Tukey's multiple comparisons test, n=3, Data presented as mean ±SE, **p=0.01 *p=0.04) ",
    "ncbi_link": "SOD: 6647"
  },
  {
    "caption": "(G) Representative images of proximity ligation assay for  CRMP4 and dynein in healthy and C9orf72 human-derived proximal  axons post peptides treatment,  Sema3A treatment, Sema3A + peptides treatment or untreated controls. Scale bar: 5µm. (H) Quantification of the  CRMP4-DIC puncta number per axon in healthy or C9orf72 human-derived MN proximal  axons after  Sema3A treatment, Sema3A + peptides  treatment or untreated controls. Data collected from 3 independent chambers in each condition. Total of 37 healthy untreated proximal axons, 61 healthy proximal  axons with  peptides treatment, 59 healthy proximal  axons  with Sema3A treatment and 52 healthy proximal axons with Sema3A  + peptides treatment. 67 C9orf72  untreated proximal axons, 63  C9orf72 proximal  axons with peptides treatment, 41 C9orf72 proximal axons with Sema3A treatment and 50 C9orf72 proximal axons with Sema3A + peptides treatment monitored. Data presented as mean ±SE. One-way ANOVA, Tukey's multiple comparisons test, n=3, ****p<0.0001. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(A) Representative images of CTX signal in healthy and  C9orf72 human IPSC-derived  MNs before and after Sema3A application. Green: denotes CTX-positive cells. Yellow circles are numbered CTX positive cells. Purple circles are cells that are missing post Sema3A treatment. Scale bar: 40 μm. (B-C) Quantification of CTX  signal in healthy and C9orf72 IPSC-derived  MNs before and 3 days after applying Sema3A to distal compartment, compared with untreated control. 3 independent chambers in each condition were analyzed. Average of ~150 neurons per condition monitored. Student's t-test, n=3, Data presented as mean ±SE, *p<0.05. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(D) Representative images of CTX signal in WT or  SOD1G93A primary  MNs before and 2 days after Sema3A  application to the distal compartment in the presence of either Dynein inhibitor+Sema3A, Dynasore+Sema3A or untreated. Green: denotes  CTX-positive cells. Yellow circles are numbered CTX  positive cells. Purple circles are cells that are missing post Sema3A treatment. Scale bar: 30 μm. (E) Quantification of CTX signal in a SOD1G93A explant before and 2 days after  Sema3A  application to the distal compartment in the presence of either Dynein  inhibitor+Sema3A, Dynasore+Sema3A. 3 independent chambers in each condition were analyzed. ~200 neurons were monitored per each condition. One-way ANOVA, Tukey's multiple comparisons test, n = 3, Data presented as mean ±SE, *p<0.05, **p<0.01.  Dynein inhibitor and Dynasore treatments were used as a negative control. ",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(A) Representative images and insets of P90 WT and SOD1G93A SC cross sections at P90. Blue: denotes  DAPI, Red: denoted NeuN, and White: denotes activated caspase 3. Scale bar: 20 µm.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(C) Representative images of P90 SOD1G93A mice SC  cross sections that were injected with AAV9-GFP/AAV9-50aa-GFP. Blue: denotes DAPI, Red: denoted NeuN, and White: denotes  activated caspase 3. Scale bar: 10 µm.",
    "ncbi_link": "GFP: 
SOD1: 6647"
  },
  {
    "caption": "(B) Expression of GFP, lncRNA-c1, GFP-lncRNA-c1, lncRNA-c2 and GFP-lncRNA-c2 (x-axis) in 8 day 4-OHT treated, miRNA depleted cells (KO) relative to ethanol treated (WT) mESC (y-axis) 24h hours post-transfection. Four independent biological replicates were treated, transfected and analyzed by RT-qPCR. Statistical significance represented on the figure based on comparison of KO/WT fold change in expression of GFP, with GFP-lncRNA-c1 and with GFP-lncRNA-c2, (paired two-tailed t-test p-value= 0.034 and 0.032 respectively) and based on comparison of KO/WT fold change in expression of GFP-lncRNAc1 with lncRNA-c1 and GFP-lncRNA-c2 with lncRNA-c2 (paired two-tailed t-test p-value= 0.012 and 0.018 respectively). Data is represented as mean±SD and Each point corresponds to the results of one independent biological replicate. Data information: For all RTqPCR analyses, transcript expression was first normalized by the amount of Act-β and PolII and next by the total amount of transfected vectors per cell estimated based on the levels of relative Neomycin expression. Each point corresponds to the results of one independent biological replicate. Statistics: NS- p-value> 0.05, *-p-value<0.05, **-p-value<0.01 and ***-p-value<0.001.",
    "ncbi_link": "GFP: 
lncRNA-c1: 
lncRNA-c2: 
lncRNAc1: 
PolII: 
Act-β: "
  },
  {
    "caption": "(C) Expression of GFP-lncRNA-c1 ΔMRE relative to GFP-lncRNA-c1 (y-axis) in ethanol treated (WT, circles) or 4-OHT treated, miRNA-depleted cells (KO, triangles, x-axis). Four independent biological replicates were treated, transfected and analyzed by RTqPCR. Data is represented as mean±SD and Each point corresponds to the results of one independent biological replicate. Paired two-tailed t-test p-value= 0.0071 Data information: For all RTqPCR analyses, transcript expression was first normalized by the amount of Act-β and PolII and next by the total amount of transfected vectors per cell estimated based on the levels of relative Neomycin expression. Each point corresponds to the results of one independent biological replicate. Statistics: NS- p-value> 0.05, *-p-value<0.05, **-p-value<0.01 and ***-p-value<0.001.",
    "ncbi_link": "Act-β: 
lncRNA-c1: 
PolII: 
GFP: "
  },
  {
    "caption": "(F) Immunoblot analysis of GFP (GFP) in protein extracts from mESCs transfected with mock, BoxB(-30)-GFP and GFP expressing vectors. ACTIN-β (ACT-β) was used as an internal control. One representative blot is depicted (G) Fold-change (FC) in normalized expression of GFP-lncRNA-c1, GFP-lncRNA-c2 (noBoxB, circles) and BoxB(-30)-GFP-lncRNA-c1, BoxB (-30)-GFP-lncRNA-c2 (BoxB(-30), triangles) (x-axis) 4-OHT treated, miRNA depleted mESCs (KO) relative to ethanol treated mESCs (WT) (y-axis). Four independent biological replicates were analyzed. Data is represented as mean±SD and Each point corresponds to the results of one independent biological replicate. Paired two-tailed t-test p-value= 0.0494 for GFP-lncRNA-c1 and p-value=0.0355 for GPF-lncRNA-c2Data information: Uncropped blots used for assembly of panels F are provided in Figure 4 Source Data.",
    "ncbi_link": "lncRNA-c2: 
BoxB: 
GFP: 
GPF: 
lncRNA-c1: "
  },
  {
    "caption": "(H) Immunoblot analysis of GFP (GFP) in protein extracts from mESCs transfected with mock, BoxB(+339)-GFP and GFP expressing vectors. ACTIN-β (ACT-β) was used as an internal control. One representative blot is depicted. (I) Fold-change (FC) in normalized expression of GFP-lncRNA-c1, GFP-lncRNA-c2 (noBoxB, circles) and BoxB(+339)-GFP-lncRNA-c1, BoxB (+339)-GFP-lncRNA-c2 (BoxB(+339), triangles) (x-axis) in 8 day 4-OHT treated, miRNA depleted mESCs (KO) relative to ethanol treated mESCs (WT) (y-axis). Four independent biological replicates analyzed.Data information: Uncropped blots used for assembly of panels H are provided in Figure 4 Source Data.",
    "ncbi_link": "lncRNA-c2: 
BoxB: 
GFP: 
lncRNA-c1: "
  },
  {
    "caption": "A-B Representative image of a proliferative cell in the DG labeled with an anti-PH3 antibody (green) (A) and quantification of the number of PH3+ cells in the DG of WT and Tau-/- mice (B) (mean ± SEM; n= 10 mice WT, n= 8 mice Tau-/-; Student´s t-test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "C-D Representative image of an apoptotic cell in the DG labeled with an anti-fractin antibody (red) (C) and quantification of the number of fractin+ cells in the DG of WT and Tau-/- mice (D) (mean ± SEM; n= 10 mice WT, n= 8 mice Tau-/-; Student´s t-test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "E-F Schematic diagram of the cell survival experimental design using thymidine analogs (F) and quantification of the percentage of surviving cells in Tau-/- mice as compared to WT mice at each cell age (1-, 2-, 4-, 6- and 8-week-old cells) (F) (mean ± SEM (normalized data); Student´s t-test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "H Quantification of the percentage of 1-, 4- and 8-week-old newborn neurons that express the DCX neuroblast marker and the NeuN mature neuron marker in WT and Tau-/- mice (χ2 test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "I-J Representative images of progenitor cells in the DG labeled with anti-Sox2 (red) and anti-BLBP (green) antibodies (I), and neuroblasts and immature neurons labeled with anti-DCX (red) and anti-calretinin (green) antibodies, respectively (J).K-N Quantification of the number of Sox2+ (K), BLBP+ (L), DCX+ (M) and calretinin+ (N) cells in the DG of WT and Tau-/- mice (mean ± SEM; n= 10 mice WT, n= 8 mice Tau-/-; Student´s t-test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "A Representative images of 4-week-old newborn granule neurons of WT and Tau-/- mice infected by a PSD95-GFP-expressing retrovirus. A schematic representation of Sholl´s analysis is shown in the WT image.B-C Quantification of total dendritic length (B) and Sholl´s analysis (C) of 4-week-old newborn granule neurons in WT and Tau-/- mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "D Representative images of 8-week-old newborn granule neurons of WT and Tau-/- mice infected by a PSD95-GFP-expressing retrovirus.E-F Quantification of total dendritic length (E) and Sholl´s analysis (F) of 8-week-old newborn granule neurons in WT and Tau-/- mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "G Representative images of 4-week-old newborn granule neurons of WT and Tau-/- mice infected by a PSD95-GFP-expressing retrovirus and their corresponding high-power magnifications showing PSDs (green).H-IQuantification of the number of PSDs/µm (H) and PSD area (I) in each dendritic branching order of 4-week-old newborn granule neurons in WT and Tau-/- mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "J Representative images of 8-week-old newborn granule neurons of WT and Tau-/- mice infected by a PSD95-GFP-expressing retrovirus and their corresponding high-power magnifications showing PSDs (green).K-L Quantification of the number of PSDs/µm (K) and PSD area (L) in each dendritic branching order of 8-week-old newborn granule neurons in WT and Tau-/- mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "A Representative traces of mEPSCs recorded at a holding potential of −65 mV from WT (black traces) and Tau-/- (red traces) mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "B Exemplary traces of mEPSCs from one cell from WT (black trace) and Tau-/- (red trace) mice.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "C Resting membrane potential of WT and Tau-/- mice (mean ± SEM; n= 13 cells WT, n= 10 cells Tau-/-; *0.05 > p ≥ 0.01, Student´s t-test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "D-E mEPSC amplitude (D) and mEPSC frequency (E) of WT and Tau-/- animals (mean ± SEM; n= 13 cells WT, n= 10 cells Tau-/-; Student´s t test or Mann-Whitney´s U test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "F Cumulative probability plot of the total mEPSC amplitudes, small mEPSCs (i) and big mEPSCs (ii) from both WT and Tau-/- mice (black and red traces, respectively) (***p < 0.001; Kolmogorov-Smirnov Z test).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "C Representative images of 1-week-old newborn granule neurons labeled with CldU (green) belonging to WT CNP, WT P, Tau-/- CNP, and Tau-/- P mice. Cell nuclei were labeled with DAPI (blue). Scale bar 50 µm.D-E Quantification of the number of 1-week-old CldU+ cells (D) and apoptotic fractin+ cells (E) in each experimental group.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "B Representative images of 8-week-old newborn granule neurons of WT CNP, WT P, Tau-/- CNP, and Tau-/- P mice infected with a PSD95-GFP-expressing retrovirus. In the WT CNP image a schematic representation of Sholl´s analysis is shown.C-D Quantification of total dendritic length (C) and Sholl´s analysis (D) of 8-week-old newborn granule neurons (n= 3 mice per experimental condition).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "E-F Representative images of an 8-week-old newborn granule neuron, in which proximal dendrites are highlighted (E), and of PSDs (green) in proximal dendrites belonging to WT CNP, WT P, Tau-/- CNP, and Tau-/- P mice (F).G-H Quantification of the number of PSDs/µm (G) and PSD area (H) in each dendritic branching order of 8-week-old newborn granule neurons (n= 3 mice per experimental condition).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "I-J Representative Western Blot (I) and quantification (J) of the levels of GluR1 subunit of AMPA receptors in hippocampi of WT and Tau-/- mice subjected or not to the Porsolt test (n= 6 mice per experimental condition).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "L-M Representative images (L) and quantification of the area (M) of MFTs of 8-week-old newborn neurons in the CA3 region of WT CNP, WT P, Tau-/- CNP, and Tau-/- P mice (n= 3 mice per experimental condition). Arrows indicate MFTs.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "C-D Representative images of DCX+ cells in the DG of CH and EE animals (C), and quantification of the number of DCX+ cells of WT and Tau-/- animals in CH or EE conditions (D).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "E Representative images of 8-week-old newborn granule neurons labeled with IdU (red) belonging to WT CH, WT EE, Tau-/- CH and Tau-/- EE mice.F-G Quantification of the number of 8-week-old IdU+ cells (F) and apoptotic fractin+ cells (G).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "A Representative images of the whole hippocampus showing GABAergic innervation labeled with GAD-65 antibody (red), and high-power magnifications of the DG molecular layer showing GAD-65+ terminals in WT CH, Tau-/- CH, WT EE and Tau-/- EE mice. Cell nuclei were labeled with DAPI (blue). White scale bar 300 µm. Red scale bar 50 µm. Green scale bar 5 µm.B-C Quantification of the density (B) and area (C) of GAD-65+ terminals in the molecular layer of mice in each experimental condition (n= 10 mice WT CH, n= 8 miceTau-/- CH, n= 6 mice WT EE, n= 10 miceTau-/- EE).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "B Representative images of 8-week-old newborn granule neurons of WT CH, WT EE, Tau-/- CH, and Tau-/- EE mice infected with a PSD95-GFP-expressing retrovirus. In the WT CH image a schematic representation of Sholl´s analysis is shown.C-D Quantification of total dendritic length (C) and Sholl´s analysis (D) of 8-week-old newborn granule neurons (n= 3 mice per experimental condition).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "E-F Representative images of an 8-week-old newborn granule neuron in which proximal and distal dendrites are highlighted (E) and of PSDs (green) in distal and proximal dendrites of WT and Tau-/- mice housed under either CH or EE conditions (F).G-H Quantification of the number of PSDs/µm (G) and PSD area (H) in each dendritic branching order of 8-week-old newborn granule neurons (n= 3 mice per experimental condition).",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "J-K Representative images (J) and quantification of the area (K) of MFTs of 8-week-old newborn neurons in the CA3 region of WT CH, WT EE, Tau-/- CH, and Tau-/- EE mice (n= 3 mice per experimental condition). Arrows indicate MFTs.",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "GFP-ATG8a expressing seedlings in Murashige & Skoog (MS) growth medium or 30 min after treatment with MS containing ACC, ABA, ATP, BL, 6-BA, Flg22, NAA or PEP1. (A) Representative maximum intensity projection images of 10 Z-stacks per image. Scale bar: 10 µm.",
    "ncbi_link": "GFP: 
ATG8a: 828287"
  },
  {
    "caption": "GFP-ATG8a expressing seedlings in Murashige & Skoog (MS) growth medium or 30 min after treatment with MS containing ACC, ABA, ATP, BL, 6-BA, Flg22, NAA or PEP1. (B) Quantification of GFP foci per 0.0025 mm2. Values are presented as mean ± standard deviation of the mean and were calculated from at least three independent experiments with 3 individuals per replicate. Bars marked with an asterisk (*) are statistically significant (P<0.05) according to the T -test.",
    "ncbi_link": "GFP: 
ATG8a: 828287"
  },
  {
    "caption": "GFP-ATG8a expressing seedlings in Murashige & Skoog (MS) growth medium or 30 min after treatment with MS containing ACC, ABA, ATP, BL, 6-BA, Flg22, NAA or PEP1. (C) GFP-ATG8a cleavage immunoblot for plants exposed to the same treatments as in (A). Numbers below the blots represent ratio for given sample normalized to input and relative to non-treated control. Experiments were repeated minimum 3 times with similar results.",
    "ncbi_link": "GFP: 
ATG8a: 828287"
  },
  {
    "caption": "GFP-ATG8a expressing seedlings in Murashige & Skoog (MS) growth medium or 30 min after treatment with MS containing ACC, ABA, ATP, BL, 6-BA, Flg22, NAA or PEP1. (D) NBR1 immunoblot for atg2-2 samples for given treatments. Numbers below the blots represent ratio for given sample normalized to input and relative to non-treated control. Experiments were repeated minimum 3 times with similar results.",
    "ncbi_link": "GFP: 
ATG8a: 828287
atg2: 821453"
  },
  {
    "caption": "(B) Pattern correlation used to find proteins that accumulate upon ABA/NAA treatment and are removed in WT but not in atg2 after swapping to flg22/6-BA.",
    "ncbi_link": "atg2: 821453"
  },
  {
    "caption": "Protein clusters obtained after quantitative proteomics of WT (green) and atg2-2 (magenta) samples treated as described (C) Protein cluster fitting the pattern displayed (D) Protein cluster for proteins that accumulate to higher levels in atg2 than WT upon treatment with flg22.",
    "ncbi_link": "atg2: 821453"
  },
  {
    "caption": "Protein clusters obtained after quantitative proteomics of WT (green) and atg2-2 (magenta) samples treated as described (E) Protein cluster of proteins which accumulate upon NAA treatment and are removed in WT but not in atg2 after swapping to 6-BA (F) Protein cluster for proteins that accumulate to higher levels in atg2 than WT upon treatment with 6-BA.",
    "ncbi_link": "atg2: 821453"
  },
  {
    "caption": "(B) Dry weight of WT, atg5-1 or atg2-2 plants grown under stable (21/16 ºC 16/8-h photoperiod) or following the Swedish Spring of 2013. Box plots: centerlines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend to the minimum and maximum. Significance calculated by Kruskal-Wallis or Feltz and Miller test for the equality of coefficients of variation as explained in materials and methods. Asterisks represent significant pairwise differences ( ∗∗∗∗P< 0.0001) (C) Box plots displaying the heterogeneity of samples in (B). Box plots: centerlines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend to the minimum and maximum. Significance calculated by Kruskal-Wallis or Feltz and Miller test for the equality of coefficients of variation as explained in materials and methods. Asterisks represent significant pairwise differences (∗∗P < 0.01, ∗∗∗∗P< 0.0001) ",
    "ncbi_link": "atg5: 831594
atg2: 821453"
  },
  {
    "caption": "(A) Representative images of root explants from WT, atg2-2 and atg5-1 in CIM (6 days) or CIM + SIM (6 + 21 days). Scale bar: 2 cm",
    "ncbi_link": "atg5: 831594
atg2: 821453"
  },
  {
    "caption": "(A) Representative images of root explants from WT, atg2-2 and atg5-1 in CIM (21 days) or CIM + SIM (21+ 21 days or 21+ 35 days). Scale bar: 2 cm",
    "ncbi_link": "atg5: 831594
atg2: 821453"
  },
  {
    "caption": "F. Genomic tracks showing aggregated accessibility of single-cell ATAC-seq clusters at the t (tbxt), tfap2a, gsc, ctcf, lhx1 and sox11 loci.",
    "ncbi_link": "ctcf: 100101689
gsc: 549458
lhx1: 100101708
sox11: 493415
tbxt: 493501
tfap2a: 395064"
  },
  {
    "caption": "A. Heat map showing log2 fold expression changes of differentially expressed genes in AC tissues overexpressing Foxb1, Foxb1-Eomes, Eomes, Irx3,  Irx3-Otx2, Otx2  and  Lhx8.",
    "ncbi_link": "Eomes: 100038065
Foxb1: 100125219
Irx3: 407888
Lhx8: 548653
Otx2: 548931"
  },
  {
    "caption": "(E) Cytokine expression levels of Tnfa, Ifng, Il1a, and Il1b were measured by RT-qPCR normalized by Ppia. Data are presented as mean ± SEM, N = 4 mice per group. *, p < 0.05 by unpaired Student's t-test with two sided.",
    "ncbi_link": "Ifng: 15978
Il1a: 16175
Il1b: 16176
Ppia: 268373
Tnfa: 21926"
  },
  {
    "caption": "(D-E) Catalytically active sACE22.v2.4-IgG1 and catalytically dead sACE22.v2.4(NN)-IgG1 were aerosolized (7.5 ml protein at 8.3 mg/ml in 25 minutes) and delivered by inhalation to K18-hACE2 transgenic mice at 12 h, 48 h, and 84 h post-inoculation with SARS-CoV-2 gamma variant. 10 mice in each group were observed for survival (D) and weight loss (E). The P-value of survival curve by Gehan-Breslow-Wilcoxon test is shown. Error bars for mouse weight are centered on the mean and show SEM. Catalytically active and inactive proteins were tested in the same experiment versus PBS control shown in Figure 1.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(C) Neutralization of BA.1 omicron pseudovirus. sACE22-IgG1 (grey) or sACE22.v2.4-IgG1 (blue) were incubated with pseudovirus for 1 h before adding to HeLa-hACE2-11 cells. Infection 48 h later was measured by luciferase reporter gene expression. Data are mean ± SD, N = 3 independent biological replicates.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(D-E) Authentic BA.1 omicron virus (isolate USA/MD-HP20874/2021) was incubated with sACE22-IgG1 (D) or sACE22.v2.4-IgG1 (E) for 1 h and added to Calu-3 cells. Infection 48 h later was measured by RT-qPCR for the viral N gene. 3 µM remdesivir (black columns) is a positive neutralization control.",
    "ncbi_link": "N gene: 43740575"
  },
  {
    "caption": "(E) Viral Spike, Nsp, and Rdrp mRNA levels in lung tissue were measured by RT-qPCR at Days 8 and 14, normalized to Ppia transcript levels. Data are presented as mean ± SEM, N = 4 mice per group. ns, not significant; **, p < 0.01 by two-ways ANOVA, corrected by Tukey.",
    "ncbi_link": "Nsp: 43740575
Rdrp: 43740578
Ppia: 268373
Spike: 43740568"
  },
  {
    "caption": "(C) BA.2 omicron pseudovirus was incubated with sACE22-IgG1 (grey) or sACE22.v2.4-IgG1 (blue) for 1 h and added to HeLa-hACE2-11 cells. Infection was measured after 48 h.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Low magnification views of a CD1 Otof-/- organ of Corti (P23) transduced with otoferlin dual‑AAV‑TS vectors. IHCs: inner hair cells, OHCs: outer hair cells maximum intensity projections of confocal optical sections",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "High magnification views of CD1B6F1 Otof-/- IHCs transduced with otoferlin dual‑AAV‑TS (P26) (B) and dual‑AAV‑Hyb (P26) (C) vectors. Individual eGFP and otoferlin immunostainings are depicted as color lookup tables in (A-C) with warmer colors representing higher pixel intensities ), maximum intensity projections of confocal optical sections",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "Percentage of N‑ and C‑terminal otoferlin labelled IHCs in dual‑AAV‑TS (n=10 mice) and dual‑AAV‑Hyb (n=9 mice) injected CD1B6F1 Otof-/- mice (P18‑30)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Average N-terminal and C‑terminal otoferlin immunofluorescence levels in dual‑AAV transduced Otof-/- and wild-type IHCs (P23-30). Otoferlin levels were normalized to immunofluorescence levels in non-transduced B6 wild-type IHCs for each antibody separately",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "High magnification views of IHCs immunolabeled for otoferlin and synaptic ribbons (CtBP2) from wild‑type (B6: P27, CD1B6F1: P29), dual-AAV injected CD1B6F1 Otof-/- (dual-AAV-TS: P26, dual-AAV-Hyb: P28), and their contralateral non-injected ears. (*) Transduced cells. Maximum intensity projections of optical confocal sections. Scale bars: 5 µm",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Synaptic ribbon numbers quantified from IHCs in apical cochlear turns of wild‑type (B6: n=48 IHCs, CD1B6F1: n=108 IHCs), transduced Otof-/- (dual‑AAV‑TS: n=59 IHCs, dual-AAV-Hyb: n=37 IHCs), and non-transduced Otof-/- IHCs from injected (-AAV injected ear, n=65 IHCs) and contralateral non-injected (-AAV non-injected ear, n=46 IHCs) ears (P25-29)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "IHC synapses labelled with CtBP2 and the postsynaptic marker Shank1a in B6 wild-type and Otof-/- P6 and P14 organs of Corti. Maximum intensity projections of optical confocal sections. Scale bars: 5 µm. D Synapse numbers quantified from IHCs in apical cochlear turns (C) of B6 wild-type (P6: n= 53 IHCs; P14: n=73 IHCs) and B6 Otof-/- (P6: n=62 IHCs; P14: n=65 IHCs) mice at two different developmental stages (P6 and P14)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Ca2+‑current-voltage relationship of control CD1B6F1 wild‑type (n=6 IHCs), dual-AAV-TS transduced (n=8 IHCs), and non‑transduced CD1B6F1 Otof-/- (n=10 IHCs) IHCs (P14‑18)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Representative Ca2+‑currents (Ica) and IHC plasma membrane capacitance increments (ΔCm) of a wild‑type control, transduced, and non‑transduced Otof-/- IHC in response to a 20 ms depolarization pulse at maximum Ca2+‑current potentials (typically -14 mV)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Average exocytosis level measured as ΔCm (G) and corresponding Ca2+‑current integrals (QCa2+) (H) in wild‑type (CD1B6F1: n=6 IHCs; B6: n=11 IHCs (B6 data replotted from Strenzke et al, 2016)), dual-AAV-TS transduced Otof-/- (n=8 IHCs), and non‑transduced (n=11 IHCs) Otof-/- IHCs. Transduced IHCs that showed eGFP expression, but had almost no exocytosis are depicted as dashed lines (not included into the average)",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Representative ABR wave traces in response to broadband click sound stimuli from otoferlin dual‑AAV‑TS and dual‑AAV‑Hyb injected CD1B6F1 Otof-/- animals. AAV2/6.eGFP (+AAV.eGFP) and dual‑AAV‑TS injected CD1B6F1 wild‑type, and non‑injected control Otof-/- littermate (-AAV) mice served as controls. SP: summating potential; ABR waves are indicated from I-V",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "ABR click sound (C thresholds in otoferlin dual‑AAV treated Otof-/- mice compared to wild‑type and non‑treated Otof-/- control animals",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "ABR tone burst (D) thresholds in otoferlin dual‑AAV treated Otof-/- mice compared to wild‑type and non‑treated Otof-/- control animals. In D, the two best animals are depicted with open circles. Animals with thresholds exceeding the maximum loudspeaker output (arrows) of 100 dB SPL for clicks and 90 dB SPL for tone bursts were set to 110 dB SPL and 100 dB SPL, respectively. Apical and basal cochlear turns are indicated as Apex and Base, respectively",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "Summed ABR wave I-V amplitudes at different click sound intensities in otoferlin dual‑AAV injected, non‑injected Otof-/-, and wild‑type control mice",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "Summed ABR wave I‑V amplitudes of individual dual‑AAV‑TS treated CD1B6F1 Otof-/- animals (n=8 animals plotted against their full-length otoferlin IHC transduction rate",
    "ncbi_link": "Otof: 83762
otoferlin: 83762"
  },
  {
    "caption": "A. Top: DDX42 KO and CTRL KO U87-MG/CD4/CXCR4/Cas9/Firefly cells were generated using 3 sgRNAs and 4 non-targeting sgRNAs, respectively (for CTRL, the average of data obtained with 4 cell populations is shown). Cells were treated or not with IFN 24 h prior to infection with HIV-1 Renilla (NL4-3/Nef-IRES-Renilla). Relative luminescence results for IFN-treated and -untreated conditions are shown. Two-way ANOVA on log-transformed data with Sidak's test. Bottom: Immunoblot analysis of DDX42 levels is shown for 1 CTRL and DDX42-depleted populations; Actin served as a loading control.",
    "ncbi_link": "Cas9: 69900935
CD4: 920
CXCR4: 7852
DDX42: 11325
Nef: 156110"
  },
  {
    "caption": "C. DDX42 silencing efficiency measured by RT-qPCR (top) and immunoblot (bottom) in parallel samples from B.",
    "ncbi_link": "DDX42: 11325"
  },
  {
    "caption": "G. Primary CD4+ T cells were electroporated with Cas9-sgRNA RNPs using 2 non-targeting sgRNAs (sgCTRL1 and 2) and 5 sgRNAs targeting DDX42. Top: Cells were then infected with HIV-1 Renilla (NL4-3/Nef-IRES-Renilla) and relative infection efficiencies obtained with cells from 3 donors are shown. Two-way ANOVA on log-transformed data with Dunnett's test. Bottom: DDX42 protein levels were determined by immunoblot, Actin served as a loading control. A representative immunoblot is shown.",
    "ncbi_link": "Cas9: 69900935
DDX42: 11325
Nef: 156110"
  },
  {
    "caption": "K. HEK293T were co-transfected with pRPS-GFP and a Flag-Firefly- (negative control) or Flag-DDX42-coding plasmid, followed by Flag immunoprecipitation and immunoblot analysis. A representative immunoblot is shown.",
    "ncbi_link": "Flag: 
GFP: "
  },
  {
    "caption": "F. The following biotinylated RNAs were used to pull-down recombinant DDX42 poly(I:C), CHIKV G4, TRF2 G4 and a mutated TRF2 G4 sequence (Mut. TRF2 G4), and DDX42 was revealed by an immunoblot.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": " A. Deep coverage exome sequencing Integrative Genomics Viewer (IGV) view of CBL c.2322T>G in DNA sample that was derived from CD31 selected cells from pleural effusion fluid. The alternate allele fraction was 4% (20/493). ",
    "ncbi_link": "CBL: 867
CD31: 5175"
  },
  {
    "caption": "(C-D-E) mRNA levels for Bdnf (C), Snap25 (D) in cortex and hippocampus; Complexin II (E) in cortex, hippocampus and striatum from a subset of WT (n=4), R6/2-untreated (n=7) and R6/2-chol animals (n=3). As no differences were found between R6/2 mice treated with saline or treated with empty g7-NPs, data were pooled.",
    "ncbi_link": "Bdnf: 12064
Complexin II: 12890
Snap25: 20614"
  },
  {
    "caption": "(C-D) mRNA levels of hmgcr and fdft1 in liver and lung of WT (n=7), R6/2-untreated (n=8) and R6/2-Chol (n=4) mice. As no differences were found between R6/2 mice treated with saline or treated with empty g7-NPs, data were pooled.",
    "ncbi_link": "fdft1: 14137
hmgcr: 15357"
  },
  {
    "caption": "B) Larval brains at 6 h ALH from grh-Gal4; UAS-CD8-GFP were labeled with Sas-4, Dpn, and GFP.",
    "ncbi_link": "Gal4: 
grh: 37038"
  },
  {
    "caption": "C) Larval brains at 0 h ALH from grh-Gal4; UAS-CD8-GFP were labeled with γ-tubulin (γ-tub), Asl, and GFP and imaged under super-resolution microscopy. D) Larval brains at 0 h ALH from grh-Gal4; UAS-CD8-GFP were labeled with Centrosomin (CNN), Asl and GFP and imaged under spinning disc super-resolution microscopy. ",
    "ncbi_link": "Gal4: 
grh: 37038"
  },
  {
    "caption": " A) Larval brains at 16 h ALH, in which kin-lacZ was expressed under the control of insc-Gal4, tub-Gal80ts, were labelled with β-Gal, Msps, and Dpn. The primary protrusion of qNSCs was marked by Msps. Quiescent NSCs at the ventral nerve cord (VNC) are shown. Arrows indicate the localization of Kin-lacZ in qNSCs. B) Larval brains at 6 h ALH from insc-Gal4; UAS-nod-lacZ were labeled with β-Gal, Msps, and Dpn. Quiescent NSCs at both CB and VNC are shown. Arrows indicate the localization of Nod-lacZ in qNSCs ",
    "ncbi_link": "Gal4: 
Gal80: 
lacZ: 
insc: 37355
kin: 36810
Kin: 36810
nod: 32107
Nod: 32107
tub: 40554"
  },
  {
    "caption": " A) Larval brains at 24 h ALH from control (insc-Gal4; UAS-dicer2/UAS-β-Gal RNAi) and msps RNAi (VDRC#21982) controlled under insc-Gal4 were analyzed for EdU incorporation. NSCs were marked by Dpn and Mira. B) Quantification graph of EdU-negative NSCs per brain lobe for genotypes in (A). n=13 BL for both control and msps RNAi. ****p< 0.0001 ",
    "ncbi_link": "Gal4: 
β-Gal: 
dicer2: 36993
insc: 37355
msps: 41952"
  },
  {
    "caption": " C) Larval brains at 24 h ALH from wild-type and various msps loss-of-function alleles and msps810 with a genomic rescue construct (g-msps) were analyzed for EdU incorporation. NSCs were marked by Dpn and Mira. D) Quantification graph of EdU-negative NSCs per brain lobe for genotypes in (C). n=13 BL for control; n=13 BL for msps810; n=17 BL for msps924; n=14 BL for mspsP18; n=6 BL for mspsP; n=12 BL for g-msps; msps924. ****p< 0.0001; p=0.7502 (ns). E) Quantification graph of the diameter of the cell body in NSCs at 24 h ALH from various genotypes. n=238 NSCs for control; n=219 NSC for msps924; n=170 NSCs for mspsP. ****p< 0.0001. F) Quantification graph of the percentage of qNSCs with a primary protrusion in wild-type, msps924, and mspsP18 larval brains. The protrusion was labelled by grh>CD8-GFP. n=5 BL for control; n=6 BL for msps924; n=4 BL for mspsP. ****p< 0.0001 ",
    "ncbi_link": "CD8: 
GFP: 
grh: 37038
msps: 41952"
  },
  {
    "caption": " G) Larval brains at 24 h ALH from wild-type and tacc loss-of-function tacc74 were examined for EdU incorporation. NSCs were marked by Dpn and Mira. H) Quantification graph of EdU-negative NSCs per brain lobe for genotypes in (G). n=17 BL for control; n=15 BL for tacc74. ****p< 0.0001. I) Quantification graph of qNSCs retaining primary protrusion per brain lobe for genotypes in (G). n=15 BL for both control and tacc74. ****p< 0.0001. J) Quantification graph of NSCs are positive for mitotic marker PH3 per brain lobe for genotypes in (G). n=15 BL for both control and tacc74. ****p< 0.0001 ",
    "ncbi_link": "tacc: 40589"
  },
  {
    "caption": " B) Quantification graph of fold changes in the number of EB1-GFP comets in the primary protrusion of qNSCs 6 h ALH from various genotypes compared with the control in (A). n=26 NSCs for control; n=18 NSCs for mspsP18; n=21 NSCs for mspsP18/P. ****p<0.0001. C) Quantification graph of the percentage of retrograde EB1-GFP comets in the primary protrusion of qNSCs from the control, mspsP18 with EB1-GFP driven by grh-Gal4 at 6 h ALH. As EB1-GFP comets were almost lost in mspsP18, we were unable to capture adequate EB1-GFP comets for each individual brain to calculate the standard deviation. 38 and 41 qNSCs were analyzed in control and mspsP18, respectively. In control qNSCs, among total 383 EB1-GFP comets, 353 were anterograde and 30 were retrograde movements. In mspsP18 qNSCs, we only found 12 EB1-GFP comets with 6 anterograde and 6 retrograde movements ",
    "ncbi_link": "Gal4: 
grh: 37038
msps: 41952"
  },
  {
    "caption": " D) Larval brains at 24 h ALH from control (grh-Gal4 UAS-CD8-GFP + UAS-nod-lacZ) and msps810,UAS-nod-lacZ under the control of grh-Gal4 UAS-CD8-GFP were labeled with β-Gal, Dpn, and GFP. Quiescent NSCs in the central brain were shown. Arrows point at the localization of Nod-lacZ in qNSCs. E) Quantification graph of Nod-β-Gal localization in qNSCs from genotypes in (D). n=55 NSCs for control; n=45 NSCs for msps810. ****p<0.0001 ",
    "ncbi_link": "CD8: 
Gal4: 
GFP: 
lacZ: 
grh: 37038
msps: 41952
nod: 32107"
  },
  {
    "caption": " F) Larval brains at 16 h ALH from control (grh-Gal4 UAS-CD8-GFP; UAS-dicer2 + UAS -nod-lacZ) and msps RNAi, UAS-nod-lacZ (VDRC#21982) with grh-Gal4 UAS-CD8-GFP; UAS-dicer2 were labeled with β-Gal, Dpn, and GFP. Quiescent NSCs in the central brain are shown. Arrows indicate the localization of Nod-lacZ in qNSCs. G) Quantification graph of Nod-β-Gal localization in qNSCs from genotypes in (F). n=60 NSCs for control; n=68 NSCs for msps RNAi. ****p<0.0001 ",
    "ncbi_link": "CD8: 
Gal4: 
GFP: 
lacZ: 
dicer2: 36993
grh: 37038
msps: 41952
nod: 32107"
  },
  {
    "caption": " H) Larval brains at 24 h ALH from wild-type control (grh-Gal4>UAS-CD8-GFP), msps924, and mspsP18 expressing grh>CD8-GFP were labeled with Dpn and GFP. The arrow indicates the second protrusion in msps924. I) Quantification graph of the thickness of the primary protrusion of qNSCs from wild-type, msps924, and mspsP18 expressing grh>CD8-GFP. The thickness was measured at the middle point of the primary protrusion. n=18 NSCs for control; n=52 NSCs for msps924; n=32 NSCs for mspsP18. **** p<0.0001 ",
    "ncbi_link": "Gal4: 
grh: 37038
msps: 41952"
  },
  {
    "caption": " L) Larval brains at 24 h ALH from control (grh-Gal4 UAS-CD8 -GFP + UAS-nod-lacZ) and tacc74,UAS-nod-lacZ under the control of grh-Gal4 UAS-CD8-GFP; tacc59 were labeled with β-Gal, Dpn, and GFP. Quiescent NSCs in the central brain are shown. M) Quantification graph of Nod-β-Gal localization in qNSCs from genotypes in (L). n=51 NSCs for control; n=65 NSCs for tacc59/74. **p=0.0051 ",
    "ncbi_link": "CD8: 
Gal4: 
lacZ: 
grh: 37038
nod: 32107
tacc: 40589"
  },
  {
    "caption": "A) Larval VNCs at 24 h ALH from the control (grh-Gal4 UAS-CD8-GFP) and msps810 with grh-Gal4 UAS-CD8-GFP were labeled with E-cadherin, Dpn, and GFP. NSC-neuropil contact were marked by dashed lines, and NSC-neuropil contact points were circled. B) Quantification of E-cadherin basal localization at NSC-neuropil contact sites in qNSCs from genotypes in (A). "No E-cad" means absent or strongly reduced E-cad observed at the basal region of qNSCs. n=32 NSCs for control; n=61 NSCs for msps810. **p=0.0028. C) Quantification graph of the basal E-cad intensity at NSC-neuropil contact sites by normalizing against Dpn intensity in qNSCs from genotypes in (A). n=34 NSCs for control; n=40 NSCs for msps810. ****p<0.0001. ",
    "ncbi_link": "Gal4: 
grh: 37038
msps: 41952"
  },
  {
    "caption": "D) Larval VNCs at 24 h ALH from control (grh-Gal4 UAS-CD8-GFP) and msps924 with grh-Gal4 UAS-CD8-GFP were labeled with E-cadherin, Dpn, and GFP. NSC-neuropil contact were marked by dashed lines, and NSC-neuropil contact sites were circled. E) Quantification of E-cadherin basal localization at NSC-neuropil contact sites in qNSCs from genotypes in (D). "No E-cad" means absent or strongly reduced E-cad observed at the basal region of qNSCs. n=77 NSCs for control; n=30 NSCs for msps924. **p=0.0080. F) Quantification graph of the basal E-cad intensity at NSC-neuropil contact sites by normalizing against Dpn intensity in qNSCs from genotypes in (D). n=60 NSCs for control; n=37 NSCs for msps924. ****p<0.0001. ",
    "ncbi_link": "Gal4: 
grh: 37038
msps: 41952"
  },
  {
    "caption": "H) Larval brains at 16 h ALH from control t-GRASP under the control of single driver grh-Gal4 or nSyb-QF2 (Q-system) and t-GRASP under the control of driver pairs grh-Gal4 and nSyb-QF2 (Q-system) were analyzed for E-Cad, GFP (reconstituted GFP), and Dpn. Arrows pointing at the cell body of qNSCs on the two different focal planes. NSC-neuropil contact sites were circled by dashed lines.",
    "ncbi_link": "Gal4: 
QF2: 
grh: 37038
nSyb: 38196"
  },
  {
    "caption": " A) Larval brains at 16 h ALH from wild-type (yw) and E-cadR69 were analyzed for EdU incorporation, and larval brains were labeled with EdU, Dpn and Mira ",
    "ncbi_link": "E-cad: 37386"
  },
  {
    "caption": " E) Larval brains at 24 h ALH from the wild-type control (yw) and klp64Dk5h/Df, kap3V6 and kap3 V6; g-kap3#11 were stained with EdU, Dpn, and Mira",
    "ncbi_link": "kap3: 32071
klp: 38515"
  },
  {
    "caption": " I) Larval brains at 24h ALH from wild-type control (yw), klp64Dk5/Df, and kap3V5 were analyzed E-cad at the NSC-neuropil contact sites, and NSCs were labeled with Dpn and Msps ",
    "ncbi_link": "kap3: 32071
klp: 38515"
  },
  {
    "caption": "A) Larval brains at 24 h ALH from wild-type control (UAS-β-Gal RNAi; UAS-β-Gal RNAi), msps RNAi control (UAS-GFP + UAS-msps RNAi (21982)), and rescued animals (UAS-klp64D+ msps RNAi (21982)) under the control of insc-Gal4 were analyzed for EdU incorporation, and larval brains were labeled with EdU and Dpn. B) Quantification graph of EdU-negative NSCs per brain lobe for genotypes in (A). n=13 BL for contorl; n=13 BL for msps RNAi; n=20 BL for UAS-klp64D + msps RNAi. ****p<0.0001.",
    "ncbi_link": "Gal4: 
GFP: 
β-Gal: 
insc: 37355
msps: 41952
klp: 38515"
  },
  {
    "caption": "D) Larval brains at 24 h ALH from wild-type control (UAS-β-Gal RNAi), RNAi control (UAS-msps RNAi (21982)), and rescued animals (g-kap3 + msps RNAi (21982)) driven by insc-Gal4 were examined for EdU incorporation, and larval brains were stained with EdU and Dpn. E) Quantification graph of NSCs negative for EdU incorporation per brain lobe for genotypes in (D). n=13 BL for control; n=15 BL for msps RNAi; n=19 BL for g-kap3 + msps RNAi. ****p<0.0001. ",
    "ncbi_link": "Gal4: 
β-Gal: 
insc: 37355
kap3: 32071
msps: 41952"
  },
  {
    "caption": "G) 24 h ALH Larval brains from wild-type control (UAS-β-Gal RNAi; UAS-β-Gal RNAi), RNAi control (UAS-GFP + UAS-msps RNAi (21982)), and rescued animals (UAS-E-cad7 + msps RNAi (21982)) were assessed for EdU incorporation, and larval brains were stained with EdU and Dpn. H) Quantification graph of NSCs negative for EdU incorporation per brain lobe for genotypes in (G). n=21 BL for control; n=21 BL for msps RNAi; n=22 BL for UAS-E-cad7 + msps RNAi. ****p<0.0001. ",
    "ncbi_link": "GFP: 
β-Gal: 
msps: 41952
E-cad: 37386"
  },
  {
    "caption": "J) 24 h ALH Larval brains from wild-type control (UAS-β-Gal RNAi), mutant control (UAS-β-Gal RNAi + klp64Dk5h), and rescued animals (UAS-E-cad7 + klp64Dk5h) were processed for EdU incorporation, and larval brains were probed by with EdU, Dpn, and Mira. K) Quantification graph of NSCs negative for EdU incorporation per brain lobe for genotypes in (J). n=10 BL for control; n=12 BL for klp64Dk5h; n=10 BL for UAS-E-cad7 + klp64Dk5h. ****p<0.0001; p=0.3006 (ns). ",
    "ncbi_link": "β-Gal: 
klp: 38515
E-cad: 37386"
  },
  {
    "caption": "B-F Live confocal images of ddaC clones expressing mCD8::GFP driven by ppk-Gal4 at WP stage or 16 h APF. l(3)810 and l(3)924 mutant ddaC clones (C, E) displayed dendrite arborization defects at WP stage and pruning defects at 16 h APF. (D, F) Introduction of one genomic construct of msps, HN267/g-msps, rescued dendrite pruning defects in msps810 and msps924 clones. Red arrowheads point to the ddaC somas.",
    "ncbi_link": "HN267: 
mCD8: 12525
msps: 41952
ppk: 34843"
  },
  {
    "caption": "A Pan-neuronal driver elav-Gal4 was used to co-express GFP-Msps and TACC in postmitotic neurons. elav-Gal4 driven mCD8::GFP expression was used as a control. TACC was pulled down by GFP-Msps but not by mCD8::GFP. Alpha-tubulin was used as a loading and probing control. Neither mCD8::GFP nor GFP-Msps could pull down alpha-tubulin.",
    "ncbi_link": "GFP: 
mCD8: 12525
elav: 31000
Gal4: 855828
Msps: 41952
TACC: 40589"
  },
  {
    "caption": "D-G Confocal images of ddaC neurons expressing control RNAi (D), msps RNAi (E), tacc RNAi (F) and αTub84B RNAi (G) that were immunostained for TACC at wL3 stage. ddaC somas are labeled by dashed lines. ddaC neurons are identified by ppk-Gal4 driven mCD8::GFP (green channel) expression, as shown at the top right corner.",
    "ncbi_link": "GFP: 
αTub84B: 40848
mCD8: 12525
Gal4: 855828
msps: 41952
ppk: 34843
tacc: 40589"
  },
  {
    "caption": "I-L Confocal images of ddaC neurons expressing control RNAi (I), msps RNAi (J), tacc RNAi (K) and αTub84B RNAi (L) that were immunostained for Msps at wL3 stage. ddaC somas are labeled by dashed lines. ddaC neurons are identified by ppk-Gal4 driven mCD8::GFP (green channel) expression, as shown at the top right corner.",
    "ncbi_link": "GFP: 
αTub84B: 40848
mCD8: 12525
Gal4: 855828
msps: 41952
ppk: 34843
tacc: 40589"
  },
  {
    "caption": "N, O Protein expression of Msps and TACC in brain tissues. (N) Larval brains of msps810/mspsP transheterozygotes at early wL3 stage were immunoblotted and probed with α-Msps and α-TACC antibody. Actin blotting was used as loading control. The dot plot on the right depicts the quantitative analysis of total TACC levels in control and msps transheterozygous larvae.",
    "ncbi_link": "msps: 41952"
  },
  {
    "caption": "O Protein expression of Msps and TACC in brain tissues. (O) Adult brains of tacc59/ tacc74 transheterozygotes were immunoblotted and probed with α-Msps and α-TACC antibody. Actin blotting was used as loading and probing control. The dot plot on the right displays the quantitative analysis of total Msps level in control and tacc transheterozygotes.",
    "ncbi_link": "tacc: 40589"
  },
  {
    "caption": "A-C Live confocal images of ddaC neurons visualized by ppk-Gal4 driven mCD8::GFP expression at WP or 16 h APF. While expression of control RNAi in ddaC neurons (A) did not affect the dendrite morphogenesis nor the pruning processes, knockdown of tacc using RNAi #1 (B) or tacc59/tacc74 transheterozygous mutant (C) severely perturbed the dendrite arborization as well as pruning. Red arrowheads point to the ddaC somas.",
    "ncbi_link": "GFP: 
mCD8: 12525
Gal4: 855828
ppk: 34843
tacc: 40589"
  },
  {
    "caption": "F-H Live confocal images of ddaC neurons visualized by ppk-Gal4 driven mCD8::GFP expression at WP or 16 h APF. Simultaneous knockdown of tacc and msps via co-expressing tacc RNAi and msps RNAi (H) in the ddaC neurons did not enhance the pruning defects, compared to those neurons co-expressing control RNAi and msps RNAi (F). Red arrowheads point to the ddaC somas.",
    "ncbi_link": "GFP: 
mCD8: 12525
Gal4: 855828
msps: 41952
ppk: 34843
tacc: 40589"
  },
  {
    "caption": "Confocal images of ddaC neurons expressing UAS-mCD8::GFP, UAS-Nod-lacZ or UAS-Kin-lacZ and immunostained for β-galactosidase at wL3 stages. (A-C) Wild-type ddaC neurons (A) displayed normal distribution of Nod-lacZ signals in dendrites. In contrast, in msps810 mutants (B) and tacc59/tacc74 mutants (C), ddaC neurons exhibited altered Nod-lacZ distribution patterns, with highly enriched stainings in the somas and decreased signals in the dendrites.",
    "ncbi_link": "GFP: 
lacZ: 
UAS: 
mCD8: 12525
Kin: 36810
msps: 41952
Nod: 32107
tacc: 40589"
  },
  {
    "caption": "Confocal images of ddaC neurons (D-F) Kin-lacZ signals were present in axons but not detectable in dendrites of the control ddaC neurons (D), whereas part of the Kin-lacZ were mislocalized to dendrites in msps RNAi (E) and tacc RNAi (F) ddaC neurons. Asterisks indicate the location of ddaC somas. White arrows indicate the location of axons. Curly brackets mark the dendritic regions where fluorescence intensity of Nod-lacZ was measured. White arrowheads point to dendritically localized Kin-lacZ signals.",
    "ncbi_link": "msps: 41952
tacc: 40589"
  },
  {
    "caption": "A-F Representative kymographs depicting EB1 comet movement patterns in the proximal dendrites of ddaC neurons at 96 h AEL. Horizontal arrow indicates the direction towards the somas, and vertical arrow indicates the time. EB1::GFP expression was driven under Gal44-77. In the control ddaC neurons (A, D), EB1 comets move predominantly in retrograde direction. EB1 comets were largely diminished in msps810/mspsP mutant neurons (B). Interestingly, in msps810/mspsP18 mutants (C), tacc RNAi (E) and tacc59/tacc74 mutant (F), increased anterograde comets were detected in ddaC dendrites.",
    "ncbi_link": "Gal4: 855828
msps: 41952
tacc: 40589"
  },
  {
    "caption": "A-F Confocal images of ddaC neurons expressing UAS-mCD8::GFP (Green channel), UAS-Nod-lacZ and immunostained for β-galactosidase at wL3 stages. Simultaneous knockdown of klp10A and msps (B) significantly restored Nod-lacZ localization in the dendrites, compared to msps and control RNAi (A). ddaC neurons with colchicine treatment (D) or with Kat-60 overexpression (F) exhibited perturbed Nod-lacZ distribution with highly enriched staining in the soma and decreased signals in the dendrites. Asterisks indicate the location of ddaC somas. White arrows indicate the location of axons. Curly brackets mark the dendritic regions where fluorescence intensity of Nod-lacZ was measured.",
    "ncbi_link": "Kat-60: 53566
klp10A: 32049
msps: 41952"
  },
  {
    "caption": "G-L Live confocal images of ddaC neurons visualized by ppk-Gal4 driven mCD8::GFP expression at WP or 16 h APF. Simultaneous knockdown klp10A and msps (H) almost fully rescued the dendrite morphological defects and the pruning defects compared with the msps, control RNAi neurons. Wild type larvae fed with colchicine (J) showed pruning defects in comparison with those feed with DMSO (I). ddaC neurons with Kat-60 overexpression (L) exhibited abnormal dendrite arborization and pruning defects. Red arrowheads point to the ddaC somas.",
    "ncbi_link": "GFP: 
mCD8: 12525
Gal4: 855828
Kat-60: 53566
klp10A: 32049
msps: 41952
ppk: 34843"
  },
  {
    "caption": "-F Representative kymographs depicting EB1 comet movement patterns in the proximal dendrites of ddaC neurons at 96 h AEL. Horizontal arrow indicates the direction towards the somas, and vertical arrow indicates the time. (B) RNAi knockdown of klp10A in msps810/mspsP18 mutants restored the retrograde movement pattern of EB1 comets. MT depolymerization or severing induced by Colchicine treatment (D) or overexpression of Kat-60 (F) led to mixed MT orientation in ddaC neurons.",
    "ncbi_link": "Kat-60: 53566
klp10A: 32049
msps: 41952"
  },
  {
    "caption": "Phenotypes of 4-d-old Col, two cbf1 mutants (cbf1-1 and cbf1-2) and two CBF1-OE lines (CBF1-myc and CBF1-flag) grown at 22°C in darkness (D) or continuous W, R, FR, and B light. Scale bar = 1 mm.   Hypocotyl lengths of Col, two cbf1 mutants and two CBF1-OE lines grown at 22°C in D or continuous W, R, FR, and B light. Error bars represent SD from 20 seedlings. *P < 0.05, **P < 0.01 and ***P < 0.001 (two-tailed t-test) for the indicated genotype compared with Col. NS, not significant.   ",
    "ncbi_link": "flag: 
myc: 
cbf1: 828653
CBF1: 828653"
  },
  {
    "caption": "qRT-PCR analysis showing the relative expression of CBF1 in 4-d-old wild-type (Col) seedlings grown at 22°C in darkness (D) or continuous W, R, FR, and B light. Error bars represent SD of three technical replicates. Different letters represent significant differences by one-way ANOVA with Duncan's post hoc test (P < 0.05).",
    "ncbi_link": "CBF1: 828653"
  },
  {
    "caption": "GUS staining of 4-d-old homozygous CBF1p:GUS transgenic seedlings grown at 22°C in D or continuous W, R, FR, and B light. Scale bar = 1 mm.",
    "ncbi_link": "GUS: "
  },
  {
    "caption": "qRT-PCR data showing that CBF1 expression is induced by different light regimes. Wild-type (Col) seedlings were first grown at 22°C in D for 4 d, and then transferred to continuous W, FR, R, or B light for the indicated times ranging from 1 h to 24 h. Error bars represent SD of three technical replicates. Different letters represent significant differences by one-way ANOVA with Duncan's post hoc test (P < 0.05).",
    "ncbi_link": "CBF1: 828653"
  },
  {
    "caption": "Immunoblots showing CBF1-myc protein levels in 4-d-old CBF1-myc seedlings grown at 22°C in D or continuous W, R, FR, and B light. anti-HSP was used as a sample loading control. Numbers below the immunoblots indicate the relative band intensities of CBF1-myc normalized to those of loading control, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "myc: 
CBF1: 828653"
  },
  {
    "caption": "F, G Immunoblots showing the levels of CBF1-myc proteins after exposure to white light. CBF1-myc seedlings were first grown at 22°C for 4 d in D, and then transferred to continuous W light for the indicated time periods within 1 h (F) or ranging from 1 h to 24 h (G). anti-HSP was used as a sample loading control. Numbers below the immunoblots indicate the relative band intensities of CBF1 or CBF1-myc normalized to those of loading control, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "myc: 
CBF1: 828653"
  },
  {
    "caption": "Immunoblots showing the levels of CBF1-myc proteins after exposure to FR (H), R (I) or B (J) light. CBF1-myc seedlings were first grown at 22°C for 4 d in D, and then transferred to continuous FR, R or B light for the indicated time periods ranging from 1 h to 24 h. anti-HSP was used as a sample loading control. Numbers below the immunoblots indicate the relative band intensities of CBF1 or CBF1-myc normalized to those of loading control, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "myc: 
CBF1: 828653"
  },
  {
    "caption": "D, E Co-IP assays showing that CBF1 interacted with phyA (D) and phyB (E) in vivo. (D) homozygous CBF1-myc seedlings were first grown at 22°C in continuous FR light for 4 d, then the total proteins were extracted and subsequently treated with 5-min R light, or 5-min R light followed by 5-min FR light (R+FR) before immunoprecipitation. (E) homozygous CBF1-myc seedlings were first grown at 22°C in continuous R light for 4 d, then the total proteins were extracted and subsequently treated with 5-min FR light, or 5-min FR light followed by 5-min R light (FR+R) before immunoprecipitation. After light treatments, total proteins were incubated with anti-c-myc Affinity Gel (Sigma-Aldrich). The total and precipitated proteins were examined by immunoblotting using antibodies against myc, phyA, phyB, and RPN6, respectively. The numbers below anti-phyA and anti-phyB blots indicate the relative band intensities of co-precipitated phyA or phyB normalized to those of precipitated CBF1-myc, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "myc: 
CBF1: 828653"
  },
  {
    "caption": "Immunoblots showing the levels of PIF4 and PIF5 proteins at 22°C in 4-d-old Col, cbf1-1, cbf1-2, and CBF1-myc seedlings grown in darkness (D) or continuous W or R light. Anti-RPN6 was used as a sample loading control. numbers below the immunoblots indicate the relative band intensities of PIF4 or PIF5 normalized to those of RPN6, respectively.",
    "ncbi_link": "myc: 
cbf1: 828653
CBF1: 828653"
  },
  {
    "caption": "Phenotypes and hypocotyl lengths of 4-d-old Col, cbf1-1, pif4 pif5, cbf1 pif4 pif5, 35S:PIF4 and 35S:PIF4 cbf1 seedlings grown at 22°C in continuous W or R light. Error bars represent SD from 20 seedlings. **P < 0.01 and ***P < 0.001 (two-tailed t-test) for the indicated pairs of seedlings. Scale bar = 1 mm. NS, not significant.",
    "ncbi_link": "cbf1: 828653
pif4: 818903
PIF4: 818903
pif5: 825075"
  },
  {
    "caption": "Immunoblots showing the PIF4 protein levels in 4-d-old Col, 35S:PIF4, and 35S:PIF4 cbf1 seedlings grown at 22°C in D or continuous W or R light. Anti-RPN6 was used as a sample loading control. numbers below the immunoblots indicate the relative band intensities of PIF4 normalized to those of RPN6, respectively.",
    "ncbi_link": "cbf1: 828653
PIF4: 818903"
  },
  {
    "caption": "Yeast three-hybrid assays showing that CBF1 represses the interaction of the Pfr-phyB with PIF4 in yeast cells. AD-PIF4, phyB-BD and CBF1 were expressed in the yeast strain Y190 as indicated. The β-galactosidase activities were measured by liquid culture assays using ONPG as the substrate. Error bars represent SD of three independent yeast clones.",
    "ncbi_link": "CBF1: 828653
phyB: 816394
PIF4: 818903"
  },
  {
    "caption": "Yeast three-hybrid assays showing that CBF1 represses the interaction of the Pfr-phyB with PIF5 (B) in yeast cells. AD-PIF4, phyB-BD and CBF1 were expressed in the yeast strain Y190 as indicated. The β-galactosidase activities were measured by liquid culture assays using ONPG as the substrate. Error bars represent SD of three independent yeast clones.",
    "ncbi_link": "CBF1: 828653
phyB: 816394
PIF4: 818903"
  },
  {
    "caption": "LCI assays showing that CBF1 inhibits phyB interaction with PIF4 (C) in plant cells. Different letters represent significant differences by one-way ANOVA with Duncan's post hoc test (P < 0.05).",
    "ncbi_link": "CBF1: 828653"
  },
  {
    "caption": "LCI assays showing that CBF1 inhibits phyB interaction with PIF5 (D) in plant cells. Different letters represent significant differences by one-way ANOVA with Duncan's post hoc test (P < 0.05).",
    "ncbi_link": "CBF1: 828653"
  },
  {
    "caption": "Semi-in vivo pull-down assays showing that CBF1 inhibits phyB interaction with PIF4 (E) The total proteins extracted from 4-d-old 35S:phyB-GFP seedlings grown at 22°C in continuous R light served as the bait, and GST-PIF4 fusion proteins served as the prey. Equivalent amounts of phyB-GFP protein extract and GST-PIF4 fusion proteins, and increasing amounts of His-CBF1 were added as indicated before anti-GFP IP assays were performed. The pulled-down proteins were subjected to immunoblotting with antibodies against phyB, GST and His, respectively. Numbers below the anti-GST blots indicate the relative band intensities of co-precipitated GST-PIF4 normalized to those of precipitated phyB-GFP, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "GFP: 
His: 
CBF1: 828653
phyB: 816394"
  },
  {
    "caption": "Semi-in vivo pull-down assays showing that CBF1 inhibits phyB interaction with PIF5 (F). The total proteins extracted from 4-d-old 35S:phyB-GFP seedlings grown at 22°C in continuous R light served as the bait, and GST-PIF5 fusion proteins served as the prey. Equivalent amounts of phyB-GFP protein extract and GST-PIF5 fusion proteins, and increasing amounts of His-CBF1 were added as indicated before anti-GFP IP assays were performed. The pulled-down proteins were subjected to immunoblotting with antibodies against phyB, GST and His, respectively. Numbers below the anti-GST blots indicate the relative band intensities of co-precipitated GST-PIF5 normalized to those of precipitated phyB-GFP, respectively. The ratio of the first clear band was set to 100 for each blot.",
    "ncbi_link": "GFP: 
His: 
CBF1: 828653
phyB: 816394"
  },
  {
    "caption": "Phenotypes of Col, two cbf1 mutants (cbf1-1 and cbf1-2) and two CBF1-OE lines (CBF1-myc and CBF1-flag) grown under LD conditions at 22°C, 17°C and 4°C, respectively. The seeds of different genotypes were germinated under LD (16-h-light/8-h-dark photoperiod) conditions at 22°C for 2 d, respectively, and then grown under LD conditions at 22°C, 17°C, or 4°C, for additional 6 d. Scale bar = 1 mm.",
    "ncbi_link": "flag: 
myc: 
cbf1: 828653
CBF1: 828653"
  },
  {
    "caption": "Hypocotyl lengths of Col, two cbf1 mutants (cbf1-1 and cbf1-2) and two CBF1-OE lines (CBF1-myc and CBF1-flag) grown under LD conditions at 22°C, 17°C or 4°C. Error bars represent SD from 10 seedlings. ***P < 0.001 (two-tailed t-test) for the indicated genotype compared with Col. NS, not significant.",
    "ncbi_link": "flag: 
myc: 
cbf1: 828653
CBF1: 828653"
  },
  {
    "caption": "qRT-PCR assays showing the CBF1 transcript levels in Col seedlings grown under LD conditions at 22°C, 17°C and 4°C. Col seeds were germinated under LD conditions at 22°C for 2 d, and then grown under LD conditions at 22°C, 17°C or 4°C for additional 6 d. The samples were collected at ZT8, and then subjected to qRT-PCR assays. Error bars represent SD of three technical replicates. Different letters represent significant differences by one-way ANOVA with Duncan's post hoc test (P < 0.05).",
    "ncbi_link": "CBF1: 828653"
  },
  {
    "caption": "E, F Immunoblots showing the protein levels of PIF4 (E) and PIF5 (F) in Col, cbf1-1, cbf1-2, and CBF1-myc seedlings grown under LD conditions at 22°C, 17°C and 4°C. The seeds of different genotypes were germinated under LD conditions at 22°C for 2 d, and then grown under LD conditions at 22°C, 17°C or 4°C for additional 6 d. The samples were collected at ZT20, and then subjected to immunoblotting. Anti-RPN6 was used as a sample loading control. Numbers below the immunoblots indicate the relative band intensities of PIF4 or PIF5 normalized to those of loading control, respectively. The ratio of the first band was set to 100 for each blot.",
    "ncbi_link": "myc: 
cbf1: 828653
CBF1: 828653"
  },
  {
    "caption": "(D) Lag-times for controlled titration of aceBA expression using an inducer construct in strain NQ1350 (inset). Addition of chlorotetracycline (cTc) removes the tetR repression and induces aceBA expression. As the expression of aceB/aceA during the response (inducer added at time = 0h) is increased, lag times decrease. Bar plot shows mean lag-times (N=3 biological repeats) for different inducer concentration with error bars denoting the Standard Deviations (SD).",
    "ncbi_link": "aceA: 948517
aceB: 948512
tetR: 912848"
  },
  {
    "caption": "(A) A plasmid system (inset) is used to control the expression of the non-required gene lacZ using the strain NQ1389. lacZ expression was induced using cTc to varying degrees at the moment of glucose depletion (time = 0 h) using the indicated range of cTc concentrations. Diauxic growth conditions with glucose and acetate, same as in Fig. 1.",
    "ncbi_link": "lacZ: 945006"
  },
  {
    "caption": "(C) Steady-state growth in glucose and acetate for the WT and the motility deletion strains ΔfliC and Δflh. Growth rate differences between WT and the mutants are not significant in glucose (p-value >0.05), but are significant for growth in acetate (p-values<0.02). Additional growth conditions are shown in Fig. EV6.",
    "ncbi_link": "flh: 945442
fliC: 949101"
  },
  {
    "caption": "(D, E) Growth transitions for the motility deletion strains ΔfliC and ΔflhD are substantially faster than that for the WT strain, with (D) showing representative growth kinetics of the three strains and (E) showing mean lag-times and standard error of four independent biological replicates. Lag-times for WT are significantly different from that of ∆fliC (p-value 0.01) and ∆flhD (p-value 0.004).",
    "ncbi_link": "flhD: 945442
fliC: 949101"
  },
  {
    "caption": "(F) ∆fliC shows a 2-fold increase (p-value 0.17) and ∆flhD shows a 3-fold increase (p-value 0.02) in aceB expression compared to WT, as measured by qPCR.",
    "ncbi_link": "aceB: 948512
flhD: 945442
fliC: 949101"
  },
  {
    "caption": "Diauxic growth kinetics for growth on glucose and a different secondary carbon sources for the WT (black) and the motility deletion strains ΔfliC and ΔflhD strain (magenta and green).",
    "ncbi_link": "flhD: 945442
fliC: 949101"
  },
  {
    "caption": "Diauxic growth kinetics for growth on glucose and a different secondary carbon sources for the WT (black) and the motility deletion strains ΔfliC and ΔflhD strain (magenta and green).",
    "ncbi_link": "flhD: 945442
fliC: 949101"
  },
  {
    "caption": "(A) (left) Representative images of anti-GFAP immunostaining in Prefrontal Cortex and Amygdala from AppNL-G-F mice receiving either AAV-VHH-B9 or AAV-GFP; (right) quantification of the GFAP+ cell number in the indicated brain regions across experimental cohorts.",
    "ncbi_link": "App: 11820"
  },
  {
    "caption": "(B) (left) Representative images of anti-IBA1 immunostaining in dentate gyrus and amygdala from AppNL-G-F mice receiving either AAV-VHH-B9 or AAV-GFP; (right) quantification of the IBA1+ cell number in the indicated brain regions across experimental cohorts.",
    "ncbi_link": "App: 11820"
  },
  {
    "caption": "(A-C) MITOL-HA formed small dot-like structures following CCCP treatment. HeLa cells transiently expressing Flag-Parkin and MITOL-HA were treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry. MITOL and Tom20 (mitochondrial marker; A) signals co-localized well without CCCP treatment, whereas the MITOL-positive small dots were not coincident with Tom20, Sec61β (ER marker; B), or LAMP1 (lysosomal marker; C) after CCCP treatment. Scale bars, 10 µm. (D) MITOL-HA co-localized with catalase (peroxisome marker) following CCCP treatment. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. Arrowheads indicate representative examples of MITOL-HA co-localization with catalase. (E) Correlation statistics for the localization of MITOL-HA and Tom20, Sec61β, LAMP1, or catalase. Dots indicate individual Pearson correlation coefficient data points. In the box-plots, the center lines indicate the medians, the box limits indicate the 25th and 75th percentiles as determined in the R software package, and the whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test. (F) The line-graph shows a line scan of fluorescence through three MITOL-positive peroxisomes (red bar in Fig 1D) that clearly indicates co-localization of MITOL (green line) and catalase (magenta line). ",
    "ncbi_link": "Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(G) Peroxisomal membrane protein (PMP) 34-FusionRed also co-localized with MITOL-GFP in Parkin-expressing HeLa cells after 3 hours of CCCP treatment. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. (H) Correlation statistics for the localization of MITOL-GFP and PMP34-FusionRed. Dots indicate individual Pearson correlation coefficient data points. In the box-plots, the center lines indicate the medians, box limits indicate the 25th and 75th percentiles as determined in the R software package, and the whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test. ",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(A) MITOL-HA did not move to peroxisomes, but was rather retained on mitochondria even after CCCP treatment in HeLa cells lacking endogenous Parkin. Wild-type HeLa cells or HeLa cells stably expressing GFP-Parkin were transfected with MITOL-HA, treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-HA and anti-Tom20 antibodies. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(B) Correlation statistics for the localization of MITOL-HA and Tom20 in the absence or presence of GFP-Parkin. Dots indicate individual Pearson correlation coefficient data points. In the box-plots, the center lines indicate the medians, the box limits indicate the 25th and 75th percentiles as determined in the R software package, and the whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test.",
    "ncbi_link": "GFP: 
Parkin: 5071"
  },
  {
    "caption": "(C) MITOL was not degraded following mitochondrial depolarization. HeLa cells stably expressing 3Flag-MITOL were transfected with a GFP-Parkin plasmid or the pEGFP-C1 vector, treated with 15 µM CCCP +/- 10 µM MG132 for 3 hours, and then immunoblotted with anti-Flag, anti-ubiquitin, and anti-tubulin antibodies. Black arrowheads indicate 3Flag-MITOL in the upper panel and mono-ubiquitin in the middle panel, respectively.",
    "ncbi_link": "3Flag: 
GFP: 
pEGFP: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(A) Wild-type or PINK1 knock out (KO) HeLa cells were transfected with GFP-Parkin wild-type or the C431S mutant, treated with 15 µM CCCP, and then immuno-stained with anti-Flag and anti-catalase antibodies. Wild-type Parkin, but not the catalytically inactive Parkin (C431S) mutant, mediated 3Flag-MITOL translocation to peroxisomes following mitophagy stimulation. In PINK1 KO HeLa cells, the redistribution of MITOL to peroxisomes was not observed even in the presence of wild-type Parkin when mitochondria were damaged. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. Arrowheads indicate representative examples of MITOL-peroxisome co-localization observed only in the presence of wild-type Parkin.",
    "ncbi_link": "GFP: 
PINK1: 65018
Parkin: 5071"
  },
  {
    "caption": "(B) The redistribution of MITOL from mitochondria to peroxisomes does not require its own E3 activity. The E3-inactive MITOL Cys65Ser/Cys68Ser (CS) and H43W mutants were transfected into HeLa cells stably expressing HA-Parkin, treated with 15 µM CCCP, and then subjected to immunocytochemistry with anti-Flag and anti-catalase antibodies. After 3 hours of CCCP treatment, both the CS and H43W mutants co-localized with catalase. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. Arrowheads indicate representative examples of 3Flag-MITOL co-localization with catalase.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(C) Correlation statistics for the localization of 3Flag-MITOL and catalase in the presence of GFP-Parkin wild-type or an inactive C431S mutant. Dots indicate individual Pearson correlation coefficient data points. In the box-plots, the center lines indicate the medians, the box limits indicate the 25th and 75th percentiles as determined in the R software package, and the whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test. MITOL overlapped with catalase only in the presence of wild-type Parkin in wild-type HeLa cells. In PINK1 knockout (KO) HeLa cells, wild-type Parkin was unable to induce the peroxisomal translocation of MITOL.",
    "ncbi_link": "GFP: 
PINK1: 65018
Parkin: 5071"
  },
  {
    "caption": "(B) Peroxisomal translocation of other mitochondrial proteins such as MitoNEET/CISD1, Fis1, Miro1/2, and Tom70 (mitochondrial outer membrane proteins), and Hsp60 (mitochondrial matrix protein) was not observed in CCCP-treated cells. HeLa cells stably expressing HA-Parkin were treated with 15 µM CCCP for 3 hours, and then immuno-stained with anti-MitoNEET/CISD1, anti-Fis1, anti-Miro1/2, anti-Tom70, anti-Hsp60, and anti-catalase antibodies. Scale bars, 10 µm.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(C) A multi-spanning outer membrane protein PBR (Peripheral Benzodiazepine Receptor) did not co-localize with catalase, but did with Tom20 during mitophagy. HeLa cells stably expressing HA-Parkin were treated with 15 µM CCCP for 3 hours, and then immuno-stained with anti-Flag, anti-Tom20, and anti-catalase antibodies. Scale bars, 10 µm.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(A) siRNA-based knockdown of endogenous Tom70, Tom20, Tom40, and Sam50. HeLa cells treated with the corresponding siRNAs and immunoblotted with the indicated antibodies. AIF, Apoptosis-inducing factor.",
    "ncbi_link": "Sam50: 25813
Tom20: 9804
Tom40: 10452
Tom70: 9868"
  },
  {
    "caption": "(B) HeLa cells were immuno-stained with anti-Flag and anti-catalase antibodies after treatment of each siRNA. Tom20- and Tom40-siRNA treatment inhibited import of Su9-GFP (the targeting sequence of the FoF1 ATPase subunit 9) into the mitochondria, leading to an accumulation of Su9-GFP precursor proteins in the cytosol and cell nucleus. 3Flag-MITOL still localized to mitochondria in Tom20, Tom40, and Sam50 siRNA-treated cells. In contrast, 3Flag-MITOL dispersed into the cytosol when Tom70 was knocked down. Scale bars, 10 µm.",
    "ncbi_link": "Sam50: 25813
Tom20: 9804
Tom40: 10452
Tom70: 9868"
  },
  {
    "caption": "(C) Statistical analysis of the MITOL subcellular localization following 15 µM CCCP treatment for 3 hours in cells treated with control, Tom70, Tom20, Tom40, or Sam50 siRNAs. Su9-GFP was not imported into the mitochondria, but rather localized to the cytosol and nucleus following Tom20 and Tom40 knockdown. The number of HeLa cells with cytosol-localized Su9-GFP or 3Flag-MITOL in each siRNA experiment were determined. Data represent the mean ± s.e.m from > 100 cells in three biological replicates. (In case of Tom40, and Sam50 siRNAs, data represent the mean ± s.e.m from > 60 cells in three biological replicates.) Statistical significance was calculated using a one-tailed Welch's t-test.",
    "ncbi_link": "Sam50: 25813
Tom20: 9804
Tom40: 10452
Tom70: 9868"
  },
  {
    "caption": "(D) HeLa cells treated with siControl or siTom70 were fractionated into cytosolic and mitochondrial fractions and then immunoblotted with anti-lactate dehydrogenase (LDH), anti-Tom20, and anti-Flag antibodies. LDH was used as a cytosolic marker. Although some MITOL detached from mitochondria during fractionation, sufficient amounts of MITOL were collected in the mitochondria-enriched fraction in control cells. In contrast, almost all of the MITOL was collected in the cytosolic fraction in siTom70-treated cells.",
    "ncbi_link": "Tom70: 9868"
  },
  {
    "caption": "(A) CRISPR/Cas9 gene editing was used to generate peroxisome-null cell lines by knocking out PEX19. In wild-type HCT116 cells, catalase localized to peroxisomes (dot-like structures), whereas in PEX19 -/- cells catalase was diffusely localized throughout the cytosol, indicating loss of peroxisomes. Scale bars, 10 µm.",
    "ncbi_link": "PEX19: 5824
Cas9: 901176"
  },
  {
    "caption": "Wild-type and PEX19 -/- HCT116 cells stably expressing HA-Parkin and 3Flag-MITOL were treated with 10 µM valinomycin for 3 hours, and then subjected to immunocytochemistry with anti-Flag, anti-catalase, and anti-Hsp60 (B) antibodies. In wild-type HCT116 cells, MITOL translocated to peroxisomes, whereas MITOL remained associated with mitochondria in PEX19 -/- cells. Arrowheads indicate representative examples of 3Flag-MITOL co-localization with catalase rather than Hsp60 in wild-type HCT116 cells. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
PEX19: 5824
Parkin: 5071"
  },
  {
    "caption": "Wild-type and PEX19 -/- HCT116 cells stably expressing HA-Parkin and 3Flag-MITOL were treated with 10 µM valinomycin for 3 hours, and then subjected to immunocytochemistry with anti-Flag anti-Tom20 (C) antibodies. In wild-type HCT116 cells, MITOL translocated to peroxisomes, whereas MITOL remained associated with mitochondria in PEX19 -/- cells. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. ",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
PEX19: 5824
Parkin: 5071"
  },
  {
    "caption": "(A) siRNA-based knockdown of Pex3, Pex16, and Pex19. HeLa cell lysates treated with the indicated plasmids and siRNAs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "Pex16: 9409
Pex19: 5824
Pex3: 8504"
  },
  {
    "caption": "(B) A comparable amount of MITOL was detected in control, PEX3-, PEX16-, and PEX19-knockdown cells. HeLa cell lysates stably expressing HA-Parkin and 3Flag-MITOL treated with the corresponding siRNAs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
PEX16: 9409
PEX19: 5824
PEX3: 8504
Parkin: 5071"
  },
  {
    "caption": "(C) MITOL translocation from the mitochondria to peroxisomes is highly dependent on Pex3. HeLa cells stably expressing 3Flag-MITOL and HA-Parkin were transfected with control, PEX3, PEX16, or PEX19 siRNA, treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-Flag and anti-catalase antibodies. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
PEX16: 9409
PEX19: 5824
Pex3: 8504
PEX3: 8504
Parkin: 5071"
  },
  {
    "caption": "(A) MITOL did not merge with Hsp60 in control siRNA-treated cells, whereas most MITOL co-localized with Hsp60 in p97/VCP knockdown cells in response to mitophagy stimuli. HeLa cells stably expressing 3Flag-MITOL and HA-Parkin were transfected with control or p97/VCP siRNA, treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-Flag, anti-catalase, and anti-Hsp60 antibodies. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071
p97: 7415
VCP: 7415"
  },
  {
    "caption": "(B) HeLa cell lysates treated with control or p97/VCP siRNA were immunoblotted with anti-p97/VCP and anti-tubulin antibodies.",
    "ncbi_link": "p97: 7415
VCP: 7415"
  },
  {
    "caption": "(C) Overexpression of an p97/VCP ATP hydrolysis-defective mutant, E305Q/E578Q (p97QQ), blocked MITOL redistribution from mitochondria to peroxisomes, while overexpression of wild-type p97/VCP had no effect on MITOL redistribution. HeLa cells stably expressing GFP-Parkin were transfected with MITOL-HA and Flag-p97/VCP wild-type or p97QQ, treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-HA and anti-catalase antibodies. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. Arrowheads indicate representative examples of MITOL-peroxisome co-localization that was only observed in the presence of a functional VCP.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
MITOL: 54708
Parkin: 5071
p97: 7415
VCP: 7415"
  },
  {
    "caption": "(D) NMS-873, a specific inhibitor of p97/VCP, prevented MITOL translocation following CCCP-treatment. HeLa cells stably expressing HA-Parkin were transfected with 3Flag-MITOL, treated with 15 µM CCCP in the presence or absence of 10 µM NMS-873 for 3 hours, and then subjected to immuno-staining with anti-Flag, anti-catalase, and anti-HA antibodies. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm. Arrowheads indicate representative examples of MITOL-peroxisome co-localization that was only observed in the presence of a functional VCP.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(A) MITOL was ubiquitylated only in the presence of Parkin when the mitochondrial membrane was decreased. After 15 µM CCCP treatment for 3 hours, HeLa cells stably expressing HA-Parkin and 3Flag-MITOL were immunoprecipitated with anti-Flag magnetic beads, and then immunoblotted with the indicated antibodies. Red bars indicate ubiquitylation; the black arrowhead indicates 3Flag-MITOL.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(B) The characteristic ubiquitylation ladder was observed for wild-type MITOL, but was absent in the K268A and K54A/K268A mutants. Black arrowhead indicates 3Flag-MITOL.",
    "ncbi_link": "MITOL: 54708"
  },
  {
    "caption": "(C) The MITOL K268A and K268R mutants were targeted to mitochondria under steady-state conditions, whereas peroxisomal localization following CCCP treatment was considerably disrupted. HeLa cells stably expressing HA-Parkin were transfected with 3Flag-MITOL wild-type, K268A, or K268R mutants, treated with 15 µM CCCP for 3 hours, and then subjected to immuno-staining with anti-Flag and anti-catalase antibodies. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(D) The double K54/K268 mutation did not change the MITOL localization pattern. The subcellular localization of the MITOL K268A or K268R mutants was not drastically changed by inclusion of the K54A or K54R mutations. Scale bars, 10 µm.",
    "ncbi_link": "MITOL: 54708"
  },
  {
    "caption": "(F) The fold change in ubiquitylation of MITOL K268, K40, and K54 in valinomycin-treated samples versus untreated samples. After 3 hours of valinomycin treatment, PEX19 -/- HCT116 cells stably expressing HA-Parkin and 3Flag-MITOL were immunoprecipitated with anti-Flag magnetic beads, and then subjected to LC-MS/MS analysis for label-free quantification of ubiquitylated peptides. Error bars represent the mean ± s.e.m in three biological replicates.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
PEX19: 5824
Parkin: 5071"
  },
  {
    "caption": "(A) To generate MITOL-3Flag knock-in (KI) HCT116 cell lines, 3xFlag gene cassettes were inserted upstream of the MITOL stop codon using CRISPR/Cas9-based gene editing. Insertion of the 3Flag-tag was verified by immunoblotting with an anti-Flag antibody. Asterisk indicates a cross-reacting band.",
    "ncbi_link": "3xFlag: 
3Flag: 
MITOL: 54708
Cas9: 901176"
  },
  {
    "caption": "(B) The MITOL subcellular localization was observed in MITOL-3Flag KI HCT116 cells stably expressing HA-Parkin with anti-Flag, anti-catalase, and anti-Hsp60 antibodies. Endogenous MITOL (detectable with an anti-Flag antibody) overlapped with Hsp60 under steady-state conditions, whereas 3 hours of valinomycin (10 µM) treatment induced translocation of endogenous MITOL from mitochondria to peroxisomes. Higher magnification images of the boxed regions are shown in the bottom panel. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(F) Endogenous MITOL is ubiquitylated following valinomycin treatment. After MITOL-3Flag KI HCT116 cells stably expressing HA-Parkin were treated with valinomycin for 3 hours, the collected cell lysates were immunoprecipitated with anti-Flag magnetic beads. The immunoprecipitates were blotted using anti-Flag and anti-ubiquitin antibodies. Red bars indicate ubiquitylation; the black arrowhead indicates MITOL-3Flag.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(A) Distribution of exogenous 3Flag-MITOL in the mitochondria‐rich or peroxisome-rich fraction following cellular fractionation. HCT116 cells stably expressing HA-Parkin and 3Flag-MITOL were subjected to fractionation and detected using anti‐Tom20, anti‐PMP70, and anti‐Flag antibodies. Tom20 and PMP70 were used as mitochondrial and peroxisomal markers, respectively. The 3,000 g and 100,000 g pellets represent the mitochondria‐rich and peroxisomes-rich fractions.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "Distribution of endogenous MITOL in the mitochondria‐rich or peroxisome-rich fraction following cellular fractionation. The distribution of endogenous MITOL was examined using MITOL-3Flag knock-in HCT116 cells. Treatment of cells with valinomycin for 3 hours reduced the amount of endogenous MITOL in the mitochondria-enriched fraction, but concomitantly increased endogenous MITOL in the peroxisomes-enriched fraction.",
    "ncbi_link": "3Flag: 
MITOL: 54708"
  },
  {
    "caption": "Distribution of endogenous MITOL in the mitochondria‐rich or peroxisome-rich fraction following cellular fractionation. The distribution of endogenous MITOL was examined using MITOL-3Flag knock-in HCT116 cells. Graphic data represent results of two biological replicates. In scatter plot, dots indicate individual data points. Black dots indicate the ratio of MITOL-3Flag collected in mitochondria-enriched fractions, and red dots are the ratio of MITOL-3Flag collected in the peroxisome-enriched fractions. Mean values are also shown.",
    "ncbi_link": "3Flag: 
MITOL: 54708"
  },
  {
    "caption": "(A) HeLa cells expressing HA-Parkin and wild type 3Flag-MITOL or 3Flag-MITOL lacking C-terminal 8 amino acids (∆C8) were treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-Flag and anti-PMP70 antibodies. Expanded peroxisomes were observed in MITOL∆C8-expressing cells. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(B) 3Flag-MITOL∆C8 with the E3-inactive Cys65Ser/Cys68Ser (CS) and H43W mutations were transfected into HeLa cells stably expressing HA-Parkin, treated with 15 µM CCCP, and then subjected to immunocytochemistry with anti-Flag and anti-PMP70 antibodies. After 3 hours of CCCP treatment, both the CS and H43W mutants localized on peroxisomes but expansion was not observed. Scale bars, 10 µm.",
    "ncbi_link": "3Flag: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(C) HeLa cells expressing HA-Parkin and MITOL wild-type or ∆C8 were treated with 15 µM CCCP for 3 hours, and the number of peroxisomes was counted as PMP70-positive dots per 100 μm2. In the box-plots, dots indicate individual data points, the center lines show the medians, box limits indicate the 25th and 75th percentiles as determined by the R software package, and whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and the X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test. The abundance of peroxisomes in cells expressing MITOL∆C8 was significantly decreased as compared with cells expressing wild-type MITOL.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(D) MITOL∆C8 causes a drastic expansion of peroxisomes following CCCP treatment. HeLa cells expressing HA-Parkin and wild-type or ∆C8 MITOL were treated with 15 µM CCCP for 3 hours, and the approximate size of peroxisomes was determined as the number of pixels occupied by one peroxisome. The PMP70-positive pixels per 100 µm2 were divided by the number of peroxisomes in the same area. In the box-plots, dots indicate individual data points, the center lines show the medians, box limits indicate the 25th and 75th percentiles as determined by the R software package, and whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Means and the number of samples are shown on the box and the X-axis, respectively. Statistical significance was calculated using a one-tailed Welch's t-test.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(A and B) HeLa cells expressing HA-Parkin and MITOL∆C8 (A) or MITOL∆C8 lacking E3 activity (B) were treated with 15 µM CCCP for 3 hours, and then subjected to immunocytochemistry with anti-Flag and anti-ubiquitin antibodies. Expanded peroxisomes were ubiquitylated upon E3 activity of MITOL. Higher magnification images of the boxed regions are shown in the small panel. Scale bars, 10 µm.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "E) Representative smRNA-FISH images of RPE-1 Parental and clones for the ABCB1 gene and DAPI. The images are projections of 0,5μm sections and a total 5 μm in thickness. Scale bar, 15μm.",
    "ncbi_link": "ABCB1: 5243"
  },
  {
    "caption": "A) TLA analysis for ABCB1 contacts in RPE-1 parental and Taxol resistant clone sg6C9 covering the whole genome. Green arrow in sg6C9 shows a de novo interaction found between ABCB1 and a region in chromosome 6. B) TLA analysis for RPE-1 Parental and sg6C9. Zoom in in the region of chr6 with de novo interaction for sg6C9. Image modified from IGV viewer.",
    "ncbi_link": "ABCB1: 5243"
  },
  {
    "caption": "D) PCR products using the primers in C(1) over the ABCB1 and EEF1A1 regions in RPE-1 Parental and the different Taxol resistant clones. E) PCR products using the primers in C(2) over the specific break site in the ABCB1 promoter in RPE-1 Parental and the different Taxol resistant clones.",
    "ncbi_link": "ABCB1: 5243
EEF1A1: 1915"
  },
  {
    "caption": "G) Percentage of RPE-1 cells targeted with the ABCB1 promoter sgRNAs found with vector integration. Percentages were calculated from data in Fig 1A. Each dot represents a CFA replicate experiment. Horizontal bars represent the mean of lentiviral integratation per sgRNA.",
    "ncbi_link": "ABCB1: 5243"
  },
  {
    "caption": "A) H3K9me3 ChIP-sequencing tracks from the q21.12 arm of chromosome 7 in RPE-1 cells (Parental and Taxol-resistant clones). The ABCB1 gene region is shown in pink. Each colored track shows the H3k9me3 profile of a different Taxol-resistant clone.",
    "ncbi_link": "ABCB1: 5243"
  },
  {
    "caption": "B) H3K9me3 ChIP-qPCR in the ABCB1 promoter region. Bar graph show primer pairs amplifying the sgRNA#6 break and spanning this region (+/- base pairs) for each Taxol-resistant clone compared to the parental. Bar plots show the mean of H3K9me3 relative enrichment. Each dot represents a technical replicate (n=3).",
    "ncbi_link": "ABCB1: 5243"
  },
  {
    "caption": "A, B Western blot analysis of ΔKu80, PKAc1-3Ty (A) parasite lysates probed with αTy antibodies. Profilin (αPRF) served as loading control.",
    "ncbi_link": "Ku80: 7900417"
  },
  {
    "caption": "A, B Western blot analysis of ΔKu80, PKAr-3Ty (B) parasite lysates probed with αTy antibodies. Profilin (αPRF) served as loading control.",
    "ncbi_link": "Ku80: 7900417"
  },
  {
    "caption": "E Western blot analysis indicates that GCα-3Ty is present in three distinct isoforms. A PKG-3Ty western blot also shows three immune reactive isoforms. Catalase or actin were used as loading controls and ΔKu80 as the parental strain.",
    "ncbi_link": "Ku80: 7900417"
  },
  {
    "caption": "A Double immunofluorescence  for GFP  (green) and the BP  marker TBR2  (yellow), combined with DAPI staining  (white), of a 57 days-old chimpanzee cerebral organoid  2 days after electroporation with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and TBR2+ double-positive cells. Scale bar, 50 µm. B Quantification of the proportion of GFP+ cells that are TBR2+ in 57 days-old chimpanzee cerebral organoids   2 days after electroporation with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 9 control and 9 ARHGAP11B-transfected  cerebral organoids   of two independent batches each; error bars indicate SD; ***, P <0.001 (two-sided Student's t-test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "C Triple immunofluorescence  for GFP  (green), the cycling cell marker Ki67  (magenta) and TBR2  (yellow), combined with DAPI staining  (white), of a 59 days-old chimpanzee cerebral organoid  4 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+, Ki67+ and TBR2+ triple-positive cells. Scale bar, 50 µ D Quantification of the proportion of GFP+ cells in the SVZ/NL  that are Ki67+ and TBR2+ double-positive in 59 days-old chimpanzee cerebral organoids  4 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 8 control and 8 ARHGAP11B-transfected cerebral organoids  of four independent batches each; error bars indicate SD; *, P <0.05 (one-sided Wilcoxon rank sum test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "A Double immunofluorescence  for GFP  (green) and the radial glia marker HOPX  (yellow), combined with DAPI staining  (white), of a 59 days-old chimpanzee cerebral organoid   4 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and HOPX+ double-positive cells. Scale bar, 50 µm. B Quantification of the proportion of GFP+ cells in the SVZ/NL  that are HOPX+ in 59 days-old chimpanzee cerebral organoids   4 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 10 control and 10 ARHGAP11B-transfected cerebral organoids  of three independent batches each; error bars indicate SD; **, P <0.01 (one-sided Wilcoxon rank sum test). C Double immunofluorescence for GFP  (green) and HOPX  (yellow), combined with DAPI staining  (white), of a 61 days-old chimpanzee cerebral organoid   10 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and HOPX+ double-positive cells. Scale bar, 50 µm. D Quantification of the proportion of GFP+ cells in the SVZ/NL  that are HOPX+ in 61 days-old chimpanzee cerebral organoids  10 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 5 control and 7 ARHGAP11B-transfected cerebral organoids  of three independent batches each; error bars indicate SD; *, P<0.05 (two-sided Student's t-test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "A Double immunofluorescence  for GFP (green) and the neuron  marker Hu  (magenta), combined with DAPI staining  (white), of a 61 days-old chimpanzee cerebral organoid  10 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and Hu+ double-positive cells. Scale bar, 50 µm. B Quantification of the proportion of GFP+ cells that are Hu+ in 61 days-old chimpanzee cerebral organoids  10 days after electroporation  with GFP expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 7 control and 11 ARHGAP11B-transfected cerebral organoids of two independent batches each; error bars indicate SD; **, P <0.01 (two-sided Student's t-test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "C Double immunofluorescence  for GFP  (green) and the  deep-layer neuron  marker CTIP2  (magenta), combined with DAPI staining  (white), of a 59 days-old chimpanzee cerebral organoid  4 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and CTIP2+ double-positive cells. Scale bar, 50 µm. D Quantification of the proportion of GFP+ cells in the SVZ/NL  that are CTIP2+ in 59-days old chimpanzee cerebral organoids  4 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 10 control and 10 ARHGAP11B-transfected cerebral organoids   of two independent batches each; error bars indicate SD; ***, P <0.001 (two-sided Student's t-test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "E Double immunofluorescence  for GFP  (green) and the upper-layer neuron  marker SATB2  (magenta), combined with DAPI staining  (white), of a 66 days-old chimpanzee cerebral organoid   15 days after electroporation  with GFP  expression plasmid plus either control plasmid (top) or ARHGAP11B  expression plasmid (bottom). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and SATB2+ double-positive cells. Scale bar, 50 µm. F Quantification of the proportion of GFP+ cells in the SVZ/NL  that are SATB2+ in 66 days-old chimpanzee cerebral organoids  15 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark red) or ARHGAP11B  expression plasmid (light red). Data are the mean of 6 control and 4 ARHGAP11B-transfected cerebral organoids   of two independent batches each; error bars indicate SD; **, P <0.01 (one-sided Wilcoxon rank sum test).",
    "ncbi_link": "GFP: 
ARHGAP11B: 89839"
  },
  {
    "caption": "A Double immunofluorescence  for GFP  (green) and the thymidine  analog BrdU  (magenta, combined with DAPI staining  (white), of 57 days-old human (top panels) and chimpanzee  (bottom panels) cerebral organoids   2 days after electroporation  with GFP  expression plasmid plus either control plasmid (upper panels) or ARHGAP11A220  expression plasmid (lower panels). Tick marks indicate the borders of the VZ   and SVZ/NL; arrowheads indicate examples of GFP+ and BrdU+ double-positive cells. Scale bar, 50 µm. B Quantification of the proportion of GFP+ cells in the SVZ/NL  that are BrdU+ in 57 days-old human  (blue) and chimpanzee  (red) cerebral organoids   2 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark blue and dark red) or ARHGAP11A220 expression plasmid (light blue and light red). Data are the mean of 12 human  control, 12 human ARHGAP11A220-transfected, 9 chimpanzee  control and 8 chimpanzee ARHGAP11A220-transfected  cerebral organoids  (grown from one human  and one chimpanzee iPSC  line, respectively) of six (human) and four (chimpanzee) independent batches each; error bars indicate SD; n.s., not significant; **, P <0.01 (Kruskal Wallis test).",
    "ncbi_link": "GFP: 
ARHGAP11A: 9824"
  },
  {
    "caption": "C Double immunofluorescence  for GFP  (green) and TBR2  (yellow), combined with DAPI staining  (white), of 57 days-old human  (top panels) and chimpanzee  (bottom panels) cerebral organoids   2 days after electroporation  with GFP   expression plasmid plus either control plasmid (upper panels) or ARHGAP11A220 expression plasmid (lower panels). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and TBR2+ double-positive cells. Scale bar, 50 µm. D Quantification of the proportion of GFP+ cells in the SVZ/NL  that are TBR2+ in 57 days-old human  (blue) and chimpanzee  (red)  cerebral organoids   2 days after electroporation  with GFP  expression plasmid plus either control plasmid (dark blue and dark red) or ARHGAP11A220 expression plasmid (light blue and light red). Data are the mean of 9 human  control, 9 human ARHGAP11A220-transfected, 10 chimpanzee  control and 10 chimpanzee ARHGAP11A220-transfected cerebral organoids   (grown from one human and one chimpanzee iPSC  line, respectively) of four (human) and three (chimpanzee) independent batches each; error bars indicate SD; n.s., not significant; *, P <0.05 (Kruskal Wallis test).",
    "ncbi_link": "GFP: 
ARHGAP11A: 9824"
  },
  {
    "caption": "A Double immunofluorescence  for GFP  (green) and the bRG  marker PTPRZ1  (magenta), combined with DAPI staining  (white), of 60 days-old human forebrain organoids, generated from ARHGAP11A  plus ARHGAP11B  double-knockout clone 16. Images were obtained 10 days after electroporation  with GFP  expression plasmid plus either ARHGAP11A  plus ARHGAP11B  expression plasmids (ARHGAP11A+B-rescue, referred to as Control), ARHGAP11B  expression plasmid only (ARHGAP11B-rescue, referred to as ARHGAP11A-KO), or ARHGAP11A  expression plasmid only (ARHGAP11A-rescue, referred to as ARHGAP11B-KO). Tick marks indicate the borders of the VZ  and SVZ/NL; arrowheads indicate examples of GFP+ and PTPRZ1+ double-positive cells. Scale bar, 50 µm B Quantification of the proportion of GFP+ cells in the SVZ/NL  that are PTPRZ1+ in 60 days-old ARHGAP11A  plus ARHGAP11B  double-knockout (11A+11B KO) human forebrain organoids. Organoids  were generated from clone 16 (left) and clone j (right), and data were obtained 10 days after the indicated electroporation  with GFP  expression plasmid plus either ARHGAP11A  (11A) plus ARHGAP11B  (11B) expression plasmids (referred to as Control, as this constitutes an ARHGAP11A+B double-rescue in the 11A+11B KO organoids; dark blue), ARHGAP11B  (11B) expression plasmid only (referred to as 11A-KO, as this constitutes a selective ARHGAP11B  rescue in the 11A+11B KO organoids; light blue), or ARHGAP11A  (11A) expression plasmid only (referred to as 11B-KO, as this constitues a selective ARHGAP11A  rescue in the 11A+11B KO organoids; dark red). For clone 16, data are the mean of 8 control, 8 11A-KO and 8 11B-KO human forebrain organoids  of two independent batches each; for clone j, data are the mean of 9 control, 10 11A-KO and 8 11B-KO human forebrain organoids   of three independent batches each; error bars indicate SD; n.s., not significant; *, P <0.05; **, P <0.01; ***, P <0.001 (Kruskal Wallis test)",
    "ncbi_link": "GFP: 
ARHGAP11A: 9824
ARHGAP11B: 89839"
  },
  {
    "caption": "Images and comparison of VEGFR3 expression (presented as relative fluorescent intensity (FI)) in CD31+/LYVE-1+ lacteals of jejunum between WT and VR3iΔLEC mice. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). AU, arbitrary unit. Scale bars, 100 μm.",
    "ncbi_link": "VR3: 14257"
  },
  {
    "caption": "Images and comparisons of absolute and relative lacteal lengths in duodenum (DD), jejunum (JJ) and ileum (IL) of WT and VR3iΔLEC mice. Note that, in addition to the alterations in the lacteal lengths in VR3iΔLEC mice, diameters of the lacteal also shrank by VEGFR3 ablation. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). Scale bars, 100 μm.",
    "ncbi_link": "VEGFR3: 14257
VR3: 14257"
  },
  {
    "caption": "Images and comparisons of number of Prox1+ LECs within initial 100 μm portion in CD31+/LYVE-1+ lacteals of jejunum from WT and VR3iΔLEC mice. Dotted lines outline villi. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). Scale bars, 100 μm.",
    "ncbi_link": "VR3: 14257"
  },
  {
    "caption": "Images and comparison of proportions of each VE-cadherin LEC junctions in CD31+/LYVE-1+ lacteals in jejunum from WT and VR3iΔLEC mice. Button-like (red arrowheads) and zipper-like (open arrowheads) junctions are indicated in each magnified box in below (n = 6 mice/group, 5-10 villi/mouse). Scale bars, 25 μm.",
    "ncbi_link": "VR3: 14257"
  },
  {
    "caption": "Comparisons of serum triglyceride (TG) at indicated time points in WT and VR3iΔLEC mice (n = 6 mice/group).",
    "ncbi_link": "VR3: 14257"
  },
  {
    "caption": "Comparison of mRNA levels of VEGF-C in the whole tissue of jejunum and ileum from SPF, GF, and CONV mice (n = 3-5 mice/group).",
    "ncbi_link": "VEGF-C: 22341"
  },
  {
    "caption": "Comparison of mRNA levels of VEGF-C in sorted CD45- stromal cells and CD45+ MHCII+ F4/80+ macrophages from jejunum and ileum of vehicle-treated mice. The mean of transcription levels of VEGF-C in CD45- stromal cells was normalized to 1, and the relative levels in macrophages were presented as fold change (n = 4 mice/group).",
    "ncbi_link": "VEGF-C: 22341"
  },
  {
    "caption": "Comparisons of VEGF-C transcription level in CD45- stromal cells (left) and CD45+ MHCII+ F4/80+ macrophages (right) in jejunum and ileum of vehicle- and ABX-treated mice. The mean of transcription levels of VEGF-C in vehicle-treated mice was normalized to 1, and the relative levels in ABX-treated mice were presented as fold change (n = 5 -6 mice/group).",
    "ncbi_link": "VEGF-C: 22341"
  },
  {
    "caption": "Representative flow cytometric analysis and comparison of MHCII+ F4/80+ macrophage gated on DAPI- CD45+ cells from jejunum and ileum of WT and DTR mice (n = 5 mice/group).",
    "ncbi_link": "DTR: 735979"
  },
  {
    "caption": "Comparison of mRNA levels of VEGF-C in the whole tissue of jejunum and ileum from WT and DTR mice (n = 5 mice/group).",
    "ncbi_link": "DTR: 735979
VEGF-C: 22341"
  },
  {
    "caption": "Images and comparisons of absolute and relative lacteal lengths in duodenum (DD), jejunum (JJ) and ileum (IL) of WT and DTR mice. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). Scale bars, 100 μm.",
    "ncbi_link": "DTR: 735979"
  },
  {
    "caption": "Images and comparisons of number of Prox1+ LECs within initial 100 μm portion (upper) and VEGFR3 expression (lower, presented as relative fluorescent intensity (FI)) in CD31+/LYVE-1+ lacteals of jejunum from WT and DTR mice. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). AU, arbitrary unit. Scale bars, 100 μm.",
    "ncbi_link": "DTR: 735979"
  },
  {
    "caption": "Images and comparison of proportions of each VE-cadherin LEC junctions in CD31+/LYVE-1+ lacteals in jejunum between WT and DTR mice. Button-like (red arrowheads) and zipper-like (open arrowheads) junctions are indicated in each magnified box in below (n = 6 mice/group, 5-10 villi/mouse). Scale bars, 25 μm.",
    "ncbi_link": "DTR: 735979"
  },
  {
    "caption": "Representative flow cytometric analysis and comparison of MHCII+ F4/80+ macrophage gated on DAPI- CD45+ cells from jejunum and ileum of WT and MyD88ΔMP mice (n = 5 mice/group).",
    "ncbi_link": "MyD88: 17874"
  },
  {
    "caption": "Comparisons of mRNA levels of VEGF-C in sorted MHCII+ F4/80+ macrophages from jejunum and ileum of WT and MyD88ΔMP mice. The mean of transcription levels of VEGF-C in WT mice was normalized to 1, and the relative level in MyD88ΔMP mice were presented as fold change (n = 5 mice/group).",
    "ncbi_link": "MyD88: 17874
VEGF-C: 22341"
  },
  {
    "caption": "Images and comparisons of absolute and relative lacteal lengths in duodenum (DD), jejunum (JJ) and ileum (IL) of WT and MyD88ΔMP mice. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). Scale bars, 100 μm.",
    "ncbi_link": "MyD88: 17874"
  },
  {
    "caption": "Images and comparisons of number of Prox1+ LECs within initial 100 μm portion (upper) and VEGFR3 expression (lower, presented as relative fluorescent intensity (FI)) in CD31+/LYVE-1+ lacteals of jejunum from WT and MyD88ΔMP mice. Each dot indicates mean value of 5-10 villi. Each dot indicates mean value of 5-10 villi in a mouse (n = 6 mice/group). AU, arbitrary unit. Scale bars, 100 μm.",
    "ncbi_link": "MyD88: 17874"
  },
  {
    "caption": "Images and comparison of proportions of each VE-cadherin LEC junctions in CD31+/LYVE-1+ lacteals in jejunum between WT and MyD88ΔMP mice. Button-like (red arrowheads) and zipper-like (open arrowheads) junctions are indicated in each magnified box in below (n = 6 mice/group, 5-10 villi/mouse). Scale bars, 25 μm.",
    "ncbi_link": "MyD88: 17874"
  },
  {
    "caption": "A-C: JurkatT cells were transfected with control, FIP3.1 or FIP3.2 siRNA oligonucleotides. A: Intracellular distribution of endogenous Rab11 and Rac1 was assessed by immunofluorescence.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "Jurkat T cells were transfected with control, FIP3.1 or FIP3.2 siRNA oligonucleotides. A: Intracellular distribution of endogenous Rab11 and Rac1 was assessed by immunofluorescence.A, E, G: Three-dimensional (3D) confocal images were post-treated by deconvolution. A 0.4-µ-thick medial stack is shown. The pericentrosomal vesicular compartment is zoomed at the bottom right-hand corner.B, F, H: Population analysis of the co-localization volume between Rab11 and Rac1 within the percentriolar vesicular compartment. Each dot represents one cell. Horizontal bars represent the mean ± SEM, Mann-Whitney test was used. Images are representative of three experiments. Bar, 5 µm",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "E, F: Jurkat cells were transfected with expression vectors encoding GFP, GFP-FIP3-WT or GFP-FIP3-I738E. Endogenous Rac1 was detected by immunofluorescence.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "G: Jurkat cells were transfected with expression vectors encoding GFP, Rab11WT-GFP, or Rab11Q70L-GFP (constitutively active) or Rab11S25N-GFP (dominant negative) mutants. Endogenous Rac1 was detected by immunofluorescence.A, E, G: Three-dimensional (3D) confocal images were post-treated by deconvolution. A 0.4-µ-thick medial stack is shown. The pericentrosomal vesicular compartment is zoomed at the bottom right-hand corner.B, F, H: Population analysis of the co-localization volume between Rab11 and Rac1 within the percentriolar vesicular compartment. Each dot represents one cell. Horizontal bars represent the mean ± SEM, Mann-Whitney test was used. Images are representative of three experiments. Bar, 5 µm",
    "ncbi_link": "Rab11: 9230///8766"
  },
  {
    "caption": "A, B: Effect of FIP3 silencing on Rac1 expression. Jurkat cells were transfected with control, FIP3.1 or FIP3.2 siRNA. Three days later cells were lysed and the expression of FIP3, Rac1 and β-tubulin analyzed by western blot. The intensity of bands corresponding to FIP3 and to Rac1 was quantified by ImageJ and normalized to the β-tubulin band used as loading control. The mean ± SD of the percentage of band intensity in silenced cells with respect to controls of three independent experiments is shown.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "B: Rac1 interaction with FIP3: HEK293T cells were transfected with GFP, GFP-FIP3 WT or GFP-FIP3I738E expression vectors. 24 h later, cells were lysed and immunoprecipitated with anti-GFP Ab. Immunoprecipitates were analyzed by electrophoresis and western blot using anti-GFP Ab (top panel) or anti-Rac1 Ab (bottom panel). Total cell lysates were analyzed (100,000 cells). The position of Rac1 (20 kDa) and Ig light chain (25 kDa) polypeptides is depicted on the right side. Arrowheads at the bottom point the bands corresponding to Rac. Quantification of bands was performed with ImageJ as the percentage of intensity with respect to the total lysate bands on the left, shown below. A representative experiment out of three carried out is shown.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "JurkatT cells were transfected with expression vectors encoding: A, C: GFP, GFP-FIP3WT, or GFP-FIP3I738E. B, C: Rab11WT-GFP, Rab11Q70L-GFP (constitutively active), or Rab11S25N-GFP (dominant negative).",
    "ncbi_link": "FIP3: 8517
Rab11: 9230///8766"
  },
  {
    "caption": "C: Rab11WT-GFP, Rab11Q70L-GFP (constitutively active), or Rab11S25N-GFP (dominant negative).",
    "ncbi_link": "Rab11: 9230///8766"
  },
  {
    "caption": "D, E: or transfected with control, or FIP3.1 siRNA. Cells were allowed to form immunological synapses with SEE-pulsed Raji cells for 30 min. Intracellular distribution of endogenous Rac1 and surface distribution of CD3 were detected by immunofluorescence. 3D confocalimages were post-treated by deconvolution. A 0.4-µm-thick medial stack is shown. C, E: Population analyses of the amount of Rac1 at the immunological synapse relative to the total cellular Rac1. Each dot corresponds to one cell. Horizontal bars represent the mean ± SEM. Mann-Whitney test. Images are representative of three experiments. Bar, 5 µm.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "JurkatT cells were transfected with either control or FIP3.1 siRNA. A: Cells were allowed to form immunological synapses with SEE-pulsed Raji cells for 30 min and endogenous Lck was detected by immunofluorescence. 3D confocalimages were post-treated by deconvolution. A 0.4-µm-thick medial stack is shown.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "A, B, C: JurkatT cells transfected with siRNA control, FIP3.1 or FIP3.2 were allowed to spread on poly-lysine-coated coverslips for the indicated times. Intracellular actin was detected with FITC-coupled Phalloidin. A: A single optical section at the level of the contact surface is shown. Bar, 5 µm. B: Population analyses of the spreading area of cells at the level of the contact surface. Each dot represents one cell. Horizontal bars represent the mean ± SEM. C:Time course representation of B, showing mean ± SEM.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "D-F: Primary humanCD4T cells were transfected with control or FIP3.1 siRNA. D, E: Cells were allowed to spread on poly-lysine-coated coverslips for 5 min. Intracellular Lck was detected by immunofluoresecence. D: A single optical section at the level of the contact surface is shown. Bar, 10 µm. E: Population analyses of the spreading area of cells at the level of the contact surface.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "Jurkat T cells were transfected with control or FIP3.1 siRNA, then transfected again with empty vector or with expression vectors encoding Myc-tagged-Rac1WT, -Rac1G12V (constitutively active mutant), or -Rac1Rac1T17N (dominant negative mutant). Cells were allowed to spread on poly-lysine-coated coverslips for the indicated time and the spreading area of cells measured. A-C, H: Population analyses of the spreading area of cells at the level of the contact surface. A-C: Time course plots representing the mean ± SEM of the data shown as in I. D-G: Staining for nucleus (blue = Dapi), F-actin (green = phalloidin) and Rac1-Myc (red = anti-Myc) is shown. A single optical section at the level of the contact surface is shown. Bar, 5 µm.",
    "ncbi_link": "FIP3: 8517
Rac1: 5879"
  },
  {
    "caption": "A: Jurkat T cells transfected with control or FIP3.1 were treated 1 h with the Rac1 inhibitor NSC23766 at 100 µM and allowed to spread on poly-lysine-coated coverslips for 15 min. F-actin was detected with FITC-Phalloidin and the spreading area of cells at the contact surface was measured.",
    "ncbi_link": "FIP3: 8517
Rac1: 5879"
  },
  {
    "caption": "A: Jurkat T cells transfected with control or FIP3.1 were activated on anti-CD3-coated plastic plates in the presence of soluble anti-CD28 during 16 h. Concentration of IL2 released in the supernatant was measured by ELISA. Histograms represent the mean ± SD of three experiments. Mann-Whitney test.",
    "ncbi_link": "FIP3: 8517"
  },
  {
    "caption": "Cyclin E-expressing BJ cells were grown for 7 days with and without folate.Fork rate (Kb/min) distribution. White bars: BJ cells expressing an empty vector (n = 145); dark gray bars: BJ cells expressing the cyclin E oncogene (n = 147); light gray bars: BJ cells cultured for 7 days in a folate-free medium (n = 135); black bars: BJ cells expressing the cyclin E oncogene cultured for 7 days in a folate-free medium (n = 138).",
    "ncbi_link": "Cyclin E: 9134///898
cyclin E: 9134///898"
  },
  {
    "caption": "Cyclin E-expressing BJ cells were grown for 7 days with and without folate. Fork distance distribution (Kb). The color code is as in (A). Empty vector (n = 78); CycE (n = 79); empty vector −folate (n = 71); CycE −folate (n = 80).",
    "ncbi_link": "CycE: 9134///898
Cyclin E: 9134///898"
  },
  {
    "caption": "Cyclin E-expressing BJ cells were grown for 7 days with and without folate. Percent of origins with the indicated progression ratio between sister forks. Empty vector (n = 158); CycE (n = 155); empty vector −folate (n = 160); CycE −folate (n = 154). *P < 0.05.",
    "ncbi_link": "CycE: 9134///898
Cyclin E: 9134///898"
  },
  {
    "caption": "Cyclin E-expressing BJ cells were grown for 7 days with and without folate.Examples of nuclei with γH2AX and 53BP1 foci following cyclin E expression (CycE) (n = 65), empty vector (n = 65), folate-free medium for 7 days (empty vector −folate) (n = 67) or oncogene expression under folate-free conditions (CycE −folate) (n = 70). Red: γH2AX; green: 53BP1; blue: DAPI staining.Percent of nuclei with the indicated number of γH2AX-53BP1 co-localized foci. **P < 0.01.",
    "ncbi_link": "CycE: 9134///898
Cyclin E: 9134///898
cyclin E: 9134///898"
  },
  {
    "caption": "Cyclin E-expressing BJ cells grown for 7 days with and without folate.Immunoblotting with anti-phosphorylated ATM and anti-phosphorylated CHK1 antibodies. Anti-β-catenin and anti-actin antibodies were used as loading controls.Protein level quantification.",
    "ncbi_link": "Cyclin E: 9134///898"
  },
  {
    "caption": "Cyclin E-expressing BJ cells grown for 7 days with and without folate.Examples of nuclei with RAD51 foci following cyclin E expression (CycE) (n = 67), empty vector (n = 65), folate-free medium for 7 days (−folate) (n = 71) or oncogene expression under folate-free conditions (CycE −folate) (n = 75). Green: RAD51, blue: DAPI staining.Percent of nuclei with the indicated number of RAD51 foci (n = 66). **P < 0.01.",
    "ncbi_link": "CycE: 9134///898
Cyclin E: 9134///898
cyclin E: 9134///898"
  },
  {
    "caption": "A, B Cyclin E- and Ras (H-RasV12)-expressing 3T3 cells grown in 100 nM folate for 4 weeks and then two additional weeks in a normal medium. Control cells were grown in a normal medium for the whole period. (A) Examples of anchorage-independent growth in soft agar of 3T3 cells. (B) Average number of colonies per soft agar plate of 3T3 cells. The number of colonies per plate is expressed as the average ± SEM from three independent experiments.",
    "ncbi_link": "Cyclin E: 12448///12447
H-Ras: 15461
Ras: 15461"
  },
  {
    "caption": "C-E Ras (H-RasV12)-expressing MCF10A cells grown in 100 nM folate for 4 weeks and then two additional weeks in a normal medium. Control cells were grown in a normal medium for the whole period. (C) Examples of anchorage-independent growth in soft agar of MCF10A cells. (D) Average number of colonies per soft agar plate of MCF10A cells. The number of colonies per plate is expressed as the average ± SEM from three independent experiments. (E) Percentage of tumor-free flanks at the indicated time points after cell injection. Ten mice were injected in both sides in each group.",
    "ncbi_link": "H-Ras: 15461
Ras: 15461"
  },
  {
    "caption": "Correlation between evolutionary divergences (16S rRNA percent identity) and pairwise Pearson correlation of transcriptional profiles. Dashed line represents linear regression.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. BAT; Immunoblotting of Afadin S1795 phosphorylation (n=4-5).",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. BAT quantification of Afadin S1795 phosphorylation (n=4-5). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. sWAT; Immunoblotting of Afadin S1795 phosphorylation (n=4-5).",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. sWAT; quantification of Afadin S1795 phosphorylation (n=4-5). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. Liver; Immunoblotting of Afadin S1795 phosphorylation (n=4-5).",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. Liver quantification of Afadin S1795 phosphorylation (n=4-5). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. (G) Quantifications of phosphorylated Insulin Receptor β and phosphorylated Akt across the three tissues (n=4-5). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. (H) Quantifications of Total IRβ/tubulin in BAT, sWAT and Liver (n=5-6). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Protein lysates from 10-13-week old CTRL and FAKO (Mllt4-/-) mice following retro-orbital injection of insulin (1U) were immunoblotted and quantified. (I) Insulin-induced lipogenesis in isolated mature adipocytes from CTRL and FAKO (Mllt4-/-) mice (n=5). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "(A) CRISPR/nCas9-mediated ablation of Afadin protein levels in a clonal cell population termed Afdn-KO.",
    "ncbi_link": "Cas9: 
CRISPR: 
Afdn: 17356"
  },
  {
    "caption": "(B) Oil red O staining and gene expression of selected adipogenic genes in WT-1 and Afdn-KO differentiated adipocytes (n=3). Data are presented as means + SEM; Student's unpaired t-test and ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Afdn: 17356"
  },
  {
    "caption": "(C) Wild-type, Afdn-KO and Afdn-KO with re-expression FLAG-tagged WT I-Afadin or a non-phosphorylable form (S1795A) stimulated with vehicle or insulin (n=4) for Immunoblotting.",
    "ncbi_link": "FLAG: 
Afadin: 17356
Afdn: 17356"
  },
  {
    "caption": "(D) Acetylated α-tubulin levels in isolated mature adipocytes from CTRL and FAKO (Mllt4-/-) mice (n=4). Data are presented as means + SEM; Student's unpaired t-test and ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "(F) Immunolocalization of IR (green) and HDAC6 (red) in Afdn-KO and Afdn-KO with re-expression FLAG-tagged WT Afadin or S1795A Afadin in mature adipocytes stimulated with insulin. Nuclei were stained with DAPI (blue). Co-localization was detected by the appearance of white pixels where the red and green overlap. Scale bars: 25 µm. Representative images are shown. The ratio of IR co-localized with HDAC6 (Mandler's co-localization coefficient) was quantified (98-112 individual cells from two independent experiments). Data are presented as means + SEM; Student's unpaired t-test and ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, NS= no significance.",
    "ncbi_link": "FLAG: 
Afadin: 17356
Afdn: 17356"
  },
  {
    "caption": "(G) Immunoprecipitation of IR followed by immunoblotting using an anti-acetyl-Lys antibody in adipocytes lacking Afadin or re-expressing Afadin, with or without insulin stimulation (n=1). Representative Western blots are shown. Data are presented as means + SEM; Student's unpaired t-test and ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, NS= no significance.",
    "ncbi_link": "Afadin: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (A) Body weight. Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (B) Body composition. Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (C) Sirius Red staining of representative embedded BAT, sWAT and vWAT from mice on HFD and quantification of adipocyte areas (~1000 adipocytes/genotype). Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (D) IPGTT after 12 weeks of diet and AUC. Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (E) ITT after 13 weeks of diet and AUC Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given high-fat diet (HFD) for 16 weeks (n=5-6). (F) normalized to basal insulin. Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "Seven-week old CTRL and FAKO (Mllt4-/-) mice were given control diet (CD) or high-fat diet (HFD) for 16 weeks (n=5-6). (G) Plasma insulin levels 5 min after an IPGTT performed after 18 weeks of diet. Data are presented as means + SEM; ANOVA with Tukey or Dunnet's post hoc test: *p<0.05, **p<0.01, ***p<0.001, NS= no significance.",
    "ncbi_link": "Mllt4: 17356"
  },
  {
    "caption": "C. HEK293  cells were incubated with 5 µg of purified EVCx43- or EVCx43+ for 24 h, in the presence or absence of Bafilomycin A1 (Baf) in the last 6 h. The levels of LC3 were analyzed by WB  and are depicted on graph (LC3-II; n=4 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "Cx43: 2697"
  },
  {
    "caption": "E. HEK293  cells were incubated with EVCx43- or EVCx43+ for 24 h before WB  analysis of ATP2A2/SERCA2, a predicted target of miRNAs enriched in Cx43-containing EV. Graph depicts quantification of ATP2A2/SERCA2  levels (n=4 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "Cx43: 2697"
  },
  {
    "caption": "A. Cx43  was immunoprecipitated  (IP) from HEK293Cx43+ cells, after which interaction  with hnRNPA2B1  and hnRNPQ  was analyzed by WB.",
    "ncbi_link": "Cx43: 2697"
  },
  {
    "caption": "A. Cell free EV biogenesis  was assessed by relative protection of Cx43-luciferase. Reactions were incubated at 4ºC or 30ºC in the presence of membranes  derived from  HEK293Cx43- transiently transfected with Cx43-luciferase  and cytosol  from  HEK293Cx43- cells, except in the negative control. 1% TX100 was used to disrupt membranes, where indicated (n=3 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "luciferase: 
Cx43: 2697
Cx43: 24392"
  },
  {
    "caption": "B. Crude membranes  and cytosol  from broken  HEK293Cx43+ or HEK293Cx43- cells were mixed in an ATP regenerating system, supplemented with synthetic miR-133b  or miR-509-3p, as indicated. Graph depicts the indicated miRNAs levels, assessed by  RT-qPCR and represented as percent protected after RNAse I  digestion of unincorporated miRNAs (n=7-8 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "Cx43: 2697
miR-133b: 442890
miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "C. Co-immunoprecipitation  of endogenous  miR-133b and miR-509-3p following UV  crosslinking immunoprecipitation (CLIP) of Cx43  (n=3-5 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "miR-133b: 442890
miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "D. WB  analysis for Cx43  in samples derived by miRNAs pulldowns  performed with whole lysates of HEK293Cx43+ cells and biotinylated miR-133b and miR-509-3p (n=5 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "Cx43: 2697
miR-133b: 442890
miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "EMSA  was performed using either Cy3-labeled miR-133b (E , and Cx43  produced by in vitro translation inserted into lipid nanodiscs, For competition EMSA, an excess of unlabeled  miR-133b  was used (competitor). Empty nanodiscs  were used to control unspecific binding.",
    "ncbi_link": "miR-133b: 442890"
  },
  {
    "caption": "EMSA  was performed using either Cy3-labeled  miR-133b F) and Cx43  produced by in vitro translation inserted into lipid nanodiscs, in the presence or absence of recombinant GST-hnRNPA2B1  or GST-hnRNPQ, as indicated.",
    "ncbi_link": "miR-133b: 442890"
  },
  {
    "caption": "EMSA  was performed using either Cy3-labeled miR-509-3p (G and Cx43  produced by in vitro translation inserted into lipid nanodiscs, For competition EMSA, an excess of unlabeled miR-133b or miR-509-3p  was used (competitor). Empty nanodiscs  were used to control unspecific binding.",
    "ncbi_link": "miR-133b: 442890
miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "EMSA was performed using either Cy3-labeled miR-509-3p H) and Cx43  produced by in vitro translation inserted into lipid nanodiscs, in the presence or absence of recombinant GST-hnRNPA2B1  or GST-hnRNPQ, as indicated.",
    "ncbi_link": "miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "I. EMSA  was performed using either Cy3-labeled wild type or mutant miR-199a-3p, and Cx43-enriched membranes  prepared from C33a  parental cells (Cx43+). Cx43- membranes  were used to control unspecific binding.",
    "ncbi_link": "miR-199a-3p: 406977///406976"
  },
  {
    "caption": "Representative maximum projection images of microscopy-based miRNA-protein interaction using beads coated with GST-tagged NT/CT-Cx43,  hnRNPA2B1 or hnRNPQ, as indicated, following the addition of Cy3-labelled  miR-133b or miR-509-3p. Graph depicts quantification of total fluorescence/bead, as a measure of  protein-miRNAs binding. Scale bars 50 μm (n=2 biological replicates; average of 23 beads analyzed/condition). Data information: p-values were derived by Kruskal-Wallis (Dunn's post-hoc) test. Bars and error bars indicate mean ± SD in all graphs.",
    "ncbi_link": "miR-133b: 442890
miR-509-3p: 100126301///100126337///574514"
  },
  {
    "caption": "A. Equal amounts of EVCx43+ and EVCx43- labelled with SYTO® RNASelect™ green fluorescent stain  were incubated with HEK293Cx43+ cells for 30 min, at 37ºC. Scale bars 10 μm (n=5 biological replicates). p-values were derived by Mann-Whitney test.",
    "ncbi_link": "Cx43: 2697"
  },
  {
    "caption": "(a) HEK293 cells stably expressing GFP-DFCP1 were transfected with or without shRNA against Atg14L. The cell lysates were subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "(f) HEK293 cells were transfected with GFP-Atg14L with or without mCherry-linked dominant-negative ULK1, and these cells were cultured in complete or starvation medium for 60 min. Bars, 10 µm.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(a) HEK293 cells were simultaneously transfected with four plasmids harboring One-Strep-Flag (OSF)-tagged Atg14L, Beclin-1, hVps34, and hVps15, and Atg14L was pulled down using Strep-Tactin Sepharose beads. Empty plasmid was used as control instead of Atg14L. The precipitates were subjected to SDS-PAGE and Coomassie brilliant blue staining.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "(e) NRK cells were transiently transfected with adenovirus expressing GFP-Atg14L or GFP-Atg14L4C4A and fixed under nutrient-rich conditions. The cells were stained with anticalnexin antibody as an ER membrane marker. Higher magnification of the boxed areas is shown below. Bars, 10 µm.",
    "ncbi_link": "Atg14L: 305831"
  },
  {
    "caption": "(a) A549 cells were transiently transfected with adenovirus expressing GFP-Atg14L or GFP-Atg14LCAAX and subjected to starvation. The cells were fixed and stained with anti-Beclin-1 antibody. Higher magnification of the boxed areas is shown below.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "(b) HEK293 cells were cotransfected with MEF-hVps34 and GFP or GFP-Atg14LCAAX and stained with anti-Flag antibody. Bars, 10 µm.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "Autophagy induction by overexpressed Atg14L. A549 cells were transiently transfected with adenovirus harboring GFP-Atg14L or GFP-Atg14L4C4A. (a and b) The cells before starvation (a) or after starvation (b) were fixed and stained with anti-LC3 antibody. (c) The number of LC3-positive puncta per cell was counted, and mean ± SD values are presented. Bars, 10 µm.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "The effect of Atg14L localization on its function. (a) Atg14L knockout mouse ES cells were transfected with GFP, GFP-Atg14L, GFP-Atg14L4C4A, or GFP-ER-Atg14L4C4A of the pCAG vector and subjected to starvation. The cells were fixed and immunostained with anti-Atg16L or anti-LC3 antibodies. (b and c) The number of Atg16L-positive puncta (b) and LC3-positive puncta (c) per cell was counted in at least 10 GFP-positive cells, and mean ± SD values are presented. Bars, 10 µm.",
    "ncbi_link": "Atg14L: 100504663"
  },
  {
    "caption": "A, Genome browser images of ChIP-seq for SAGA proteins before and after induction of ER stress at ER stress response genes CHOP, ERP70, and GRP78. ATF4/Xbp1s binding sites are from publicly available datasets (GEO accessions GSE69304 and GSE49952).",
    "ncbi_link": "CHOP: 1649
GRP78: 3309
ERP70: 9601"
  },
  {
    "caption": "A, HCT116 cells were treated with 100 nM Thapsigargin for the indicated times in the presence or absence of shRNA targeting USP22. Cells were harvested and whole-cell lysate was subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "A, Genome browser images of ChIP-seq for Pol II and Ub-H2B before and after induction of ER stress, with and without USP22 knockdown, at ER stress response genes CHOP, ERP70, and GRP78. ATF4/Xbp1s binding sites are from publicly available datasets (GEO accessions GSE69304 and GSE49952).",
    "ncbi_link": "CHOP: 1649
GRP78: 3309
ERP70: 9601
USP22: 23326"
  },
  {
    "caption": "B, Metagene profiles for Pol II (upper panel) and Ub-H2B (middle panel) ChIP-seq for USP22-dependent, USP22-Bound genes. mRNA analyses of select Bound gene transcripts are presented (lower panel). Three independent experiments are represented as mean ± SEM, with significance measured by Student's t-test, *p<0.05, **p<0.01, ***p<0.005 C, Metagene profiles for Pol II (upper panel) and Ub-H2B (middle panel) ChIP-seq for USP22-dependent, SAGA-Unbound genes. Nonparametric Mann-Whitney analyses of 7 bins (grey shade) surrounding TSS (TSS) and the midpoint of the profiles (Body) in Thaps treated conditions are reported. mRNA analysis of select Unbound gene transcripts are presented (lower panel). Three independent experiments are represented as mean ± SEM, with significance measured by Student's t-test, **p<0.01, ***p<0.005. ",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "C, ChIP-qPCR for total RNA Pol II, pSer5 Pol II, and pSer2 Pol II at ERP70, GRP78, and a gene desert (Prom = gene promoter, Coding = downstream coding region - see Appendix Table S1 for primer sequences). Three independent experiments are represented as mean ± SEM. with significance measured by Student's t-test, *p<0.05, **p<0.01, ***p<0.005.",
    "ncbi_link": "GRP78: 3309
ERP70: 9601"
  },
  {
    "caption": "B, HCT116 cells were treated for 2 hrs with 100 nM Thapsigargin in the presence or absence of shRNA targeting USP22. Cells were harvested, fractionated, and fractions were subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "A, Genome browser image of ChIP-seq for middle and tail Mediator subunits and H3K4me3 HiChIP tracks before and after induction of ER stress at ER stress response gene BHLHE40. H3K4me1 and H3K27ac tracks are from the ENCODE Consortium (GEO accessions GSM945858 and GSM945853). ATF4/Xbp1s binding sites are from publicly available datasets (GEO accessions GSE69304 and GSE49952).",
    "ncbi_link": "BHLHE40: 8553"
  },
  {
    "caption": "(H)  Yeast-2-hybrid assay shows Glr1 interacts  in vivo with both Pex5  full-length and Pex5  N' domain.",
    "ncbi_link": "Pex5: 851831"
  },
  {
    "caption": "(B) Metabolomic  analysis focused on strains with over-expression or deletion of the AYT1  gene shows a significant reduction or accumulation, respectively, in  acetyl-glutamate  compared to the matched control strain of each mutant. Only metabolites changing significantly in at least one of the two conditions are presented. D-EIP  is D-erythro-1-(Imidazole-4-yl) glycerol 3-phosphate.",
    "ncbi_link": "AYT1: 850663"
  },
  {
    "caption": "(D) A  growth assay in a condition that does not induce high levels of  acetyl-CoA in peroxisomes  (glucose) shows that all strains grow similarly to the control until  stationary phase  when peroxisomes  become vital. In stationary phase, the over-expression (OE) of AYT1  grows to a lower density than the control strain, plausibly due to burdening of peroxisomal  functions. (E) A growth assay in a condition expected to elevate acetyl-glutamate  levels in peroxisomes  (oleate  as a sole carbon  source and glutamate  as a nitrogen  source) demonstrates that the AYT1  overexpressing strain grows faster and to a higher density than the control. Data information: The  growth assays in D and E were done in three biologically independent replicates and error bars were plotted. Note that some error bars are shorter than the symbol, hence are not visible in the graph.",
    "ncbi_link": "AYT1: 850663"
  },
  {
    "caption": "(G) A  β-oxidation activity assay of Δlpx1, Δfsh3, and Δlpx1Δfsh3 strains supplemented with labeled  8 carbon- or 18 carbon-free fatty acids in media supplemented with 0.5% glucose  shows a significant reduction in β-oxidation activity compared to the wild type and the two single mutants, suggesting an overlapping role for Fsh3  with Lpx1.This assay was done in three biologically independent replicates. Bars represent the mean and error bars represent the standard deviation.",
    "ncbi_link": "fsh3: 854454
Fsh3: 854454
lpx1: 854251
Lpx1: 854251"
  },
  {
    "caption": "(E)  Western blot  analysis of Fbp1-HA  levels in mutants Δpex3 (no peroxisomes), Δpex5 (abolished targeting of GID subunits to peroxisomes), and Δpex7 (no β-oxidation due to loss of Pot1  targeting) demonstrates that two hours after the transition from glucose  to ethanol  (gluconeogenic conditions), control and Δpex7 cells upregulated Fbp1-HA  levels, while for Δpex3 and Δpex5 cells Fbp1-HA  levels remain low. Antibodies were used against the HA  tag (for Fbp1) and Actin  as a loading control.",
    "ncbi_link": "pex3: 851929
pex5: 851831
pex7: 851720
Pot1: 854646"
  },
  {
    "caption": "(d) Representative images of HepG2 cells transfected with control or TSC2 siRNA immunostained for TSC2 (green) and PMP70 (red). Individual boundaries are shown to identify cells with TSC2 knockdown (white) versus cells that retain TSC2 (yellow). Scale bars, 10 μm. (e) Corresponding immunoblots for HepG2 cells transfected with control or TSC2 siRNA showing the extent of knockdown (average over population of cells). (f) HepG2 cells from d were analysed for Pearson's correlation coefficient of TSC2 co-localization with PMP70 using Imaris software. Quantification was performed on 8-12 cells from each of the 4 independent experiments, giving rise to a total of 40 cells. All error bars represent s.e.m., ***P0.001. Uncropped images of western blots are shown in Supplementary Fig. S6. Source data for the statistical analysis are shown in Supplementary Table S1.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(c) Subcellular fractionation of TSC2+/+ and TSC2−/− mouse embryonic fibroblasts (MEFs) demonstrating the localization of TSC2, TSC1, Rheb and AKT. PMP70, catalase (peroxisome fraction, P), LDH (cytosolic fraction, C), β-integrin (membrane fraction, M) and lamin A/C (nuclear fraction, N) were used as subcellular markers. Uncropped images of western blots are shown in Supplementary Fig. S6.",
    "ncbi_link": "TSC2: 22084"
  },
  {
    "caption": "(a) Western analysis of whole-cell extracts (WCE), membrane (M), cytosolic (C) and peroxisome (P) fractions from parental and MCF-7 cells stably expressing constitutively active myristoylated AKT (myr-AKT) immunoblotted for TSC2, LDH, catalase and PMP70. Light and dark represent short and long autoradiographic exposures, respectively.",
    "ncbi_link": "AKT: 10000///208///207"
  },
  {
    "caption": "(a) Representative merged images using GFP-LC3 MCF-7 cells expressing Flag-TSC1, Flag-TSC2 or both Flag-TSC1 and Flag-TSC2 showing GFP-LC3 (green) puncta. Scale bars, 10 μm. (b) Quantification of GFP-LC3 puncta was performed and the results are represented as the average puncta fluorescence per cell (±s.e.m., n = 3 independent experiments) from 100 cells per experiment as shown in a. ***P0.001; NS, not significant.",
    "ncbi_link": "LC3: 440738///81631///84557
TSC1: 7248
TSC2: 7249"
  },
  {
    "caption": "(c) Representative images of FAO cells transfected with DsRed-Del-ARL (deleted ARL sequence; red) and GFP-PTS1 (green; top panel). FAO cells were also transfected with DsRed-ARL (red) and stained for PMP70 or catalase (green) as indicated. Scale bars, 10 μm.",
    "ncbi_link": "ARL: 24855"
  },
  {
    "caption": "(d) HEK293 cells expressing Flag-TSC2 wild type (WT) or Flag-TSC2 mutants (RQ, RW and RG) were co-immunoprecipitated using anti-Flag or anti-PEX5, and blotted for PEX5 and Flag-TSC2.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(e) Representative experiment showing subcellular fractionation of HEK293 cells overexpressing Flag-TSC2 wild type and Flag-TSC2 mutants (RQ, RW and RG). Lysates from peroxisome (P) or membrane (M) fractions and whole-cell extracts (WCE) were immunoblotted with Flag or PMP70 antibodies.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(f) Co-immunoprecipitation of HEK293 cells overexpressing Flag-TSC2 wild type, or Flag-TSC2 mutant (RQ) or Flag-TSC2 rescue mutant (RQ-9NT) using anti-Flag antibody or control IgG and immunoblotted with anti-Flag and anti-PEX5 antibodies.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(g) Subcellular fractionation of TSC2−/− MEFs transfected with Flag-TSC2 wild type, or Flag-TSC2 mutants (RQ or RQ-9NT). β-integrin and catalase were used as subcellular markers for membrane and peroxisome fractions, respectively. WCE, whole-cell extract. The arrow indicates the position of overexpressed Flag-TSC2.",
    "ncbi_link": "TSC2: 22084"
  },
  {
    "caption": "(h) HEK293 cells co-transfected with Flag-TSC1 and Flag-TSC2 wild type (WT) or Flag-TSC2 G294E mutant (TSC2 mutant that cannot bind TSC1). Lysates were immunoprecipitated using anti-PEX19 and blotted for PEX19 and Flag.",
    "ncbi_link": "TSC1: 7248
TSC2: 7249"
  },
  {
    "caption": "(b) TSC2 functional assay was performed in HEK293 cells co-expressing myc-Rheb, Flag-TSC1 and Flag-TSC2 wild type (WT), or Flag-TSC2 mutants (RG, RQ and RW) and HA-S6K (left panel) or HA-4E-BP1 (right panel). Cells transfected with empty vector (EV) with or without myc-Rheb were used as controls. Lysates were further analysed for phospho-S6K (T389), S6K, phospho-4EB-P1 (S65), 4E-BP1 and 32P incorporation into S6.",
    "ncbi_link": "Rheb: 6009
TSC2: 7249"
  },
  {
    "caption": "(c) Rheb GTPase activity assays were performed by co-immunoprecipitating TSC heterodimers from HEK293 cells expressing Flag-TSC1 and TSC2-TSC2 wild type, Flag-TSC2 mutants or the Flag-TSC2 GAP mutant (L1624P), for the indicated times.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(d) TSC2 functional assay was performed using TSC2−/− MEFs co-transfected with Flag-TSC1, HA-S6K and Flag-TSC2 wild type or Flag-TSC2 mutants (RQ or RQ-9NT), with mock transfected cells as controls. Arrows denote the positions of Flag-TSC1 and Flag-TSC2. (e) Quantification of the ratio of phospho-S6K to total HA-S6K from Fig. 7d. (±s.e.m., n = 3 independent experiments). *P0.05;**P0.01.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(f) In vivo guanine nucleotide loading of Rheb was measured using HEK293 cells overexpressing Flag-TSC1 and Flag-TSC2 wild type, or Flag-TSC2 mutants (RQ and RQ-9NT) with or without Rheb as indicated. (g) Graph shows quantification of the percentage of Rheb bound to GTP (indicative of Rheb GTPase activity, ±s.e.m., n = 4 independent experiments). *P0.05;***P0.001.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(h) Quantification of axon number in hippocampal neurons co-transfected with GFP, Flag-TSC1 and Flag-TSC2 WT or Flag-TSC2 mutants. Quantification was performed on 150-250 neurons from each of the 3 independent experiment and the results are represented as polarity (%). All error bars represent s.e.m. *P0.05;**P0.01 compared with GFP-only transfected control. Uncropped images of western blots are shown in Supplementary Fig. S6. Source data for the statistical analysis are shown in Supplementary Table S1.",
    "ncbi_link": "TSC1: 60445
TSC2: 24855"
  },
  {
    "caption": "(B) Induction of the worm fat-7p::GFP metabolic reporter. Adult worms  pre-colonized with P. cellulosa were incubated in liquid media for 24 h with the indicated carbon  sources, and GFP  fluorescence was read in individual worms  on a BioSorter large object sorter. Data information: All experiments were performed in biological triplicates. Student's t test was used for statistical analysis. Student's t test was used for statistical analysis. In B, error bars represent 95% confidence intervals for the mean. In B, each point represents a different worm  in biological replicates, n=96, n=53, and n=80 from left to right.",
    "ncbi_link": "fat-7p: 
GFP: "
  },
  {
    "caption": "(A) RT-qPCR analysis of Myh7b/miR-499 and Myh7/miR-208b levels during differentiation of myoblasts into mature myotubes (n = 3 independent experiments). *p = 0.0005 (Myh7b), *p < 0.0001 (miR-499), *p = 0.0002 (Myh7), *p < 0.0001 (miR-208b).",
    "ncbi_link": "miR-208b: 100124433
miR-499: 735275
Myh7: 140781
Myh7b: 668940"
  },
  {
    "caption": "(C) Mean expression levels (RT-qPCR) in white vastus (WV) and soleus (Sol) muscle from 8-week-old male wild type mice (n = 5 mice per group). *p < 0.0001 (Myh7b), *p < 0.0001 (miR-499), *p < 0.0001 (Myh7), *p < 0.0001 (miR-208b).",
    "ncbi_link": "miR-208b: 100124433
miR-499: 735275
Myh7: 140781
Myh7b: 668940"
  },
  {
    "caption": "(E) (Left) Schematic depicts the increments of speed over time. (Right) Respiratory exchange ratio (RER) during a graded exercise regimen as described in Materials and Methods (n = 5 mice per group). Notably, MCK-miR-499 mice were able to exercise at a higher speed before exhaustion. *p < 0.05.",
    "ncbi_link": "MCK: 12715
miR-499: 735275"
  },
  {
    "caption": "(F) Bars represent mean blood lactate levels for 3-month and 15-month old male MCK-miR-499 and NTG mice following a 25 min run on a motorized treadmill. For 3-month blood lactate, NTG, n = 9; MCK-miR-499, n = 10. For 15-month blood lactate, NTG, n = 7; MCK-miR-499, n = 5. *p = 0.039 (3-month), *p = 0.018 (15-month).",
    "ncbi_link": "MCK: 12715
miR-499: 735275"
  },
  {
    "caption": "(G) Mitochondrial respiration rates were determined from the plantaris muscle of the indicated genotypes using pyruvate/malate as substrate. Pyruvate/malate (Py/M)-stimulated, ADP-dependent respiration, oligomycin-induced (oligo) and the respiratory control ratio (RC) are shown. NTG, n = 6; MCK-miR-499, n = 4. *p = 0.015 (Py/M), *p = 0.017 (ADP), *p = 0.001 (Oligo).",
    "ncbi_link": "MCK: 12715
miR-499: 735275"
  },
  {
    "caption": "(G) Cross-section of the gastrocnemius muscle from a 3-month-old male NTG and MCK-miR-499 stained for myosin I ATPase activity (Top), SDH (Middle), and α-GPDH (Bottom). Representative images were shown. Scale bar: 500 μm.",
    "ncbi_link": "MCK: 12715
miR-499: 735275"
  },
  {
    "caption": "(A) (Left) Representative western blot analysis of PGC-1α protein expression in the gastrocnemius muscle from the indicated genotypes, heart (Ht) lysate from WT mice and PGC-1α mKO (MCK-Cre) mice as positive and negative controls, respectively. (Right) Quantification of the PGC-1α/Tubulin signal ratios normalized (=1.0) to the NTG control (n = 5 mice per group). *p = 0.00017.",
    "ncbi_link": "Cre: 
MCK: 12715
PGC-1α: 19017"
  },
  {
    "caption": "(B) Expression of the Ldhb, Ldha, Mb (myoglobin), and Cox5a genes (RT-qPCR) in the gastrocnemius muscle from the indicated genotypes (n = 5 mice per group). *p < 0.001 (vs. NTG), ‡p < 0.01 (vs. 499Tg).",
    "ncbi_link": "Cox5a: 12858
Ldha: 16828
Ldhb: 16832
myoglobin: 17189"
  },
  {
    "caption": "(C) (Left) Representative western blot analysis performed with gastrocnemius muscle total protein extracts prepared from the indicated mice using cytochrome c, myoglobin, and α-tubulin (control) antibodies. (Right) Quantification of the Cyt c/Tubulin signal ratios normalized (=1.0) to the NTG control. NTG, n = 5; 499Tg, n = 6; PGC-1α mKO, n = 5; 499Tg/PGC-1α mKO, n = 5. *p < 0.01 (vs. NTG), ‡p = 0.00018 (vs. 499Tg).",
    "ncbi_link": "PGC-1α: 10891"
  },
  {
    "caption": "(E) Respiratory exchange ratio (RER) during a graded exercise regimen as described in Materials and Methods. Notably, no significant increase in exhaust speed was observed in 499Tg/PGC-1α mKO mice compared to PGC-1α mKO mice. PGC-1α mKO, n = 5; 499Tg/PGC-1α mKO, n = 8.",
    "ncbi_link": "PGC-1α: 10891"
  },
  {
    "caption": "(F) The bars represent the mean blood lactate levels from the indicated mice following a 25 min run on a motorized treadmill. NTG, n = 9; 499Tg, n = 7; PGC-1α mKO, n = 6; 499Tg/PGC-1α mKO, n = 9. *p = 0.0009 (NTG vs. 499Tg), p = 0.316 (NS, not significant).",
    "ncbi_link": "PGC-1α: 19017"
  },
  {
    "caption": "(B) Luciferase reporters containing the wild-type Fnip1 3'UTR or Fnip1 3'UTR mutated in the predicted binding site of miR-499 were used in cotransfection studies in HEK293T cells in the presence or absence of plasmid expressing miR-499 (n = 3 independent experiments). *p < 0.0001 (Fnip1 3'UTR); *p = 0.023 (Mutated).",
    "ncbi_link": "Luciferase: 
Fnip1: 216742
miR-499: 735275"
  },
  {
    "caption": "(C) RT-qPCR analysis of Fnip1 and Fnip2mRNA levels in the gastrocnemius muscle of the indicated genotypes (n = 5 mice per group).",
    "ncbi_link": "Fnip1: 216742
Fnip2: 329679"
  },
  {
    "caption": "(A) (Left) Representative western blot analysis performed on extracts of myotubes subjected to Fnip1 siRNA or control (Con) siRNA using phospho-AMPKα (Thr172) and AMPKα antibodies. (Right) Quantification of the p-AMPKα/AMPKα signal ratios (n = 3 independent experiments). *p = 0.037.",
    "ncbi_link": "Fnip1: 216742"
  },
  {
    "caption": "(B, C) Results of RT-qPCR analysis for WT primary mouse myotubes after transfection with Fnip1 siRNAs or scrambled Con siRNAs as indicated. For C, 48 h post-siRNA transfection, myotubes were treated for 24 h with DMSO or 10 μm compound C before harvest (n = 3 independent experiments). *p < 0.0001 (Fnip1 in B), *p = 0.0001 (PGC-1α in B); *p < 0.0001 (vs. Con siRNA in C), ‡p < 0.0001 (vs. Fnip1 siRNA in C ).",
    "ncbi_link": "Fnip1: 216742
PGC-1α: 19017"
  },
  {
    "caption": "(D) (Top) Representative western blot analysis performed on extracts of the gastrocnemius muscle isolated from NTG or MCK-miR-499 mice using phospho-AMPKα (Thr172), AMPKα, phospho-ACC (Ser79), or total ACC antibodies. (Bottom) Quantification of the p-AMPKα/AMPKα and p-ACC/ACC signal ratios normalized (=1.0) to the NTG control (n = 8 mice per group). *p < 0.01.",
    "ncbi_link": "MCK: 12715
miR-499: 735275"
  },
  {
    "caption": "(E) Oxygen consumption rates (OCR) in primary mouse myotubes transfected with Fnip1 siRNA or Con siRNA. n = 7 separate experiments done with 5 biological replicates. *p < 0.05 (Pyruvate), *p < 0.01 (FCCP).",
    "ncbi_link": "Fnip1: 216742"
  },
  {
    "caption": "(F) Results of RT-qPCR analysis for WT primary mouse myotubes subjected to inhibition of both miR-499 and miR-208b (Anti-miRs) (n = 4 independent experiments). *p = 0.037 (Ppargc1a), *p = 0.0019 (Fnip1).",
    "ncbi_link": "Fnip1: 216742
miR-208b: 100124433
miR-499: 735275
Ppargc1a: 19017"
  },
  {
    "caption": "(G) Oxygen consumption rates (OCR) in primary mouse myotubes transfected with miR-499/miR-208b inhibitors alone and together with the presence of Fnip1 siRNA. n = 4 separate experiments done with 5 biological replicates. *p < 0.01 (Anti-miRs vs. Control).",
    "ncbi_link": "Fnip1: 216742
miR-208b: 100124433
miR-499: 735275"
  },
  {
    "caption": "(A) Mean expression levels (RT-qPCR) in gastrocnemius muscle of 8-week-old male WT and mdx mice (n = 5 mice per group). *p = 0.009 (Myh7b), *p = 0.0007 (miR-499), *p = 0.0143 (Myh7), *p < 0.0011 (miR-208b).",
    "ncbi_link": "mdx: 13405
miR-208b: 100124433
miR-499: 735275
Myh7: 140781
Myh7b: 668940"
  },
  {
    "caption": "(C) (Left) Representative western blot analysis of PGC-1α (Top) and Fnip1 (Bottom) protein expression in the gastrocnemius muscle from the indicated genotypes with α-tubulin as the loading control. (Right) Quantification of the PGC-1α/Tubulin and Fnip1/Tubulin signal ratios normalized (=1.0) to the WT control. WT, n = 8; mdx, n = 5; mdx/499Tg, n = 7. *p < 0.0001 (vs. WT), ‡p < 0.0001 (vs. mdx).",
    "ncbi_link": "mdx: 13405
PGC-1α: 19017"
  },
  {
    "caption": "(F) 5-week-old male WT, mdx, and mdx/MCK-miR-499 mice were euthanized and serum creatine kinase activity was determined. WT, n = 10; mdx, n = 10; mdx/499Tg, n = 14. *p < 0.0001 (vs. WT), ‡p = 0.0003 (vs. mdx).",
    "ncbi_link": "MCK: 12715
mdx: 13405
miR-499: 735275"
  },
  {
    "caption": "(G) The bars represent the mean running time and distance (± SEM) for 8-week-old male mice on a motorized treadmill. WT, n = 10; mdx, n = 13; mdx/499Tg, n = 8. *p = 0.01406 (Running time, vs. WT), ‡p = 0.005756 (Running time, vs. mdx). *p = 0.004558 (Running distance, vs. WT), ‡p = 0.001668 (Running distance, vs. mdx).",
    "ncbi_link": "mdx: 13405"
  },
  {
    "caption": "(H) Respiratory exchange ratio (RER) during a graded exercise regimen on a motorized treadmill. mdx, n = 8; mdx/499Tg, n = 6. ‡p < 0.05.",
    "ncbi_link": "mdx: 13405"
  },
  {
    "caption": "(B-D) Relative protein levels of pIRE1 (B), relative mRNA levels of spliced-XBP1 (C), and relative protein levels of spliced-XBP1 (C) in control (solid circles) and Yip1A-knockdown (open circles) cells. The protein or mRNA levels in control cells at the beginning of the Tm treatment were assigned the value 1. Data are means ± SD from three independent experiments.",
    "ncbi_link": "XBP1: 7494
Yip1A: 81555"
  },
  {
    "caption": "(E) Representative immunoblots for Sar1, Sec23, Sec24D, and GAPDH, and relative protein levels of Sar1, Sec23, and Sec24D in control (solid circles), Yip1A-knockdown (open circles), and IRE1-knockdown (solid gray circles) cells. GAPDH was used for normalization. The intensity of the bands was quantified using the MultiGauge software, and the results are shown in the line graphs. The protein levels in control cells at the beginning of the Tm treatment were assigned the value 1. Data are means ± SD from three independent experiments.",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "(F) Representative confocal micrographs of control (upper panels) or Yip1A-knockdown (lower panels) cells during the Tm treatment. Fixed cells at the indicated time points were stained for pIRE1. Cells are outlined with white dashed lines. Scale bars are 10 μm. The numbers of pIRE1 foci per cell were counted, and shown in the line graph. Data are means ± SD (N = 30).",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "(G) Representative immunoblot for pIRE1 after native PAGE, showing two high-order complexes of pIRE1 (pIRE1-I and pIRE1-II). Lane 'S' represents lysate from HeLa cells transfected with control scramble siRNA, and lane 'Y' represents lysate from HeLa cells transfected with Yip1A siRNA. Numbers on the left-hand side correspond to the standard molecular weight. The intensity of the bands was quantified by using the MultiGauge software, and the results are shown in the bar graphs. Protein levels in control cells at the beginning of the Tm treatment were assigned the value 1. Data are means ± SD from three independent experiments. **: p<0.01.",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "HeLa cells were transfected with each siRNA for 24 hr, and then treated with Tm for 5 hr to induce the UPR. (A, B) Representative confocal micrographs of control (left-hand panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (right-had panels) cells after 0 hr or 5 hr of Tm treatment (A). The ER structure was visualized with an anti-calnexin antibody. Large vacuoles were observed in control cells (arrowheads), but not in Yip1A- or IRE1-knockdown cells. Scale bars are 10 μm. The percentage of cells with vacuoles was counted, and is shown in the bar graph (B). Data are means ± SD from three independent experiments (N = 100). **: p<0.01.",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "(C, D) Representative confocal micrographs of control, Atg9-knockdown, WIPI1-knockdown, and DFCP1-knockdown cells after 0 hr or 5 hr of Tm treatment (C). The ER structure was visualized with an anti-calnexin antibody. Large vacuoles were observed in control and DFCP1-knockdown cells (arrowheads), but rarely seen in Atg9- or WIPI1-knockdown cells. Scale bars are 10 μm. The percentage of cells with vacuoles was counted, and is shown in the bar graph (D). Data are means ± SD from three independent experiments (N = 100). **: p<0.01.",
    "ncbi_link": "Atg9: 285973///79065
WIPI1: 55062
DFCP1: 53349"
  },
  {
    "caption": "(B-D) Relative protein levels of pIRE1 (B) and spliced-XBP1 (C), and relative mRNA levels of spliced-XBP1 (D) in control (solid circles) and Yip1A-knockdown (open circles) cells. The protein levels at time 0 hr were assigned the value 1. Data are means ± SD from three independent experiments.",
    "ncbi_link": "XBP1: 7494
Yip1A: 81555"
  },
  {
    "caption": "(E) Representative immunoblots for pPERK, cleaved-ATF6, and GAPDH, and relative protein levels of pPERK and cleaved-ATF6 in control (solid bars) and Yip1A-knockdown (open bars) cells. GAPDH was used for normalization. The intensity of the bands was quantified using the MultiGauge software, and the results are shown in the bar graphs. As a positive control for activation of PERK or ATF6, HeLa cells were treated with 5 μg/ml tunicamycin for 8 hr ('Tm'). The protein levels at time 0 hr were assigned the value 1. Data are means ± SD from three independent experiments.",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": ". (F) Representative immunoblots for Sar1, Sec23, Sec24D, and GAPDH, and relative protein levels of Sar1, Sec23, and Sec24D in control (solid bars) and Yip1A-knockdown (open bars) cells at 24 hr p.i. GAPDH was used for normalization. The intensity of the bands was quantified using the MultiGauge software, and the results are shown in the bar graphs. The protein levels in control cells were assigned the value 1. Data are means ± SD from three independent experiments. *: p<0.05; **: p<0.01.",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "(G) Representative immunoblots for Sar1, Sec23, Sec24D, and GAPDH, and relative protein levels of Sar1, Sec23, and Sec24D in control (solid bars) and IRE1-knockdown (open bars) cells at 24 hr p.i. GAPDH was used for normalization. The intensity of the bands was quantified using the MultiGauge software, and the results are shown in the bar graphs. The protein levels in control cells were assigned the value 1. Data are means ± SD from three independent experiments. *: p<0.05; **: p<0.01.",
    "ncbi_link": "IRE1: 2081"
  },
  {
    "caption": "HeLa cells were infected with B. abortus, and then transfected with each siRNA at 1 hr p.i. (A) Intracellular growth of B. abortus within control (solid bars), Yip1A-knockdown (open bars), and IRE1-knockdown (solid gray bars) cells. CFUs were enumerated at the indicated time points. Data are means ± SD from three independent experiments. *: p<0.05; **: p<0.01.",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "(B, C) Representative confocal micrographs of control (left-hand panel) and Yip1A-knockdown (right-hand panel) cells at 24 hr p.i. (B). Fixed cells were double-stained for Yip1A (green) and B. abortus (red). The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The knockdown efficiency of Yip1A in infected cells was evaluated by quantifying the intensity of immunofluorescence staining for Yip1A, and the result is shown in the bar graph (C).",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "(D, E) Representative confocal micrographs of control (left-hand panel) and IRE1-knockdown (right-hand panel) cells at 24 hr p.i. (D). Fixed cells were double-stained for IRE1 (green) and B. abortus (red). The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The knockdown efficiency of IRE1 in infected cells was evaluated by quantifying the intensity of immunofluorescence staining for IRE1, and the result is shown in the bar graph (E).",
    "ncbi_link": "IRE1: 2081"
  },
  {
    "caption": "(F, G) Representative confocal micrographs of control (left-hand panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (right-hand panels) cells at 8 hr, 16 hr, and 24 hr p.i. (F). Fixed cells were stained for B. abortus. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. To assess the replication efficiency, the percentage of infected cells with fewer than ten B. abortus was determined at 24hr p.i., and the result is shown in the bar graph (G).",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "(A) Representative electron micrographs of Brucella-infected control (left-hand panel) and Yip1A-knockdown (right-hand panel) cells at 24 hr p.i. Insets are magnifications of the boxed areas on the main image, showing the typical forms of BCVs. In control cells, BCVs can be seen in the form of ER-derived membrane-bound compartments (inset in left-hand panel, defined as 'I'). Note the presence of ribosomes on the membrane (arrowheads). In Yip1A-knockdown cells, the bacteria were not sequestered into such compartments (inset in right-hand panel, defined as 'II'). Scale bars are 2 μm.",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "(B) Representative electron micrograph of Brucella-infected IRE1-knockdown cells at 24 hr p.i. Inset is a magnification of the boxed area in the main image, showing that the bacteria were not sequestered into ER-derived membrane. Scale bar is 2 μm.",
    "ncbi_link": "IRE1: 2081"
  },
  {
    "caption": ") The percentages of the two forms of BCVs (I and II) present in control and Yip1A-knockdown cells at 24 hr p.i. The total numbers of BCVs analyzed were 67 for control cells and 37 for Yip1A-knockdown cells.",
    "ncbi_link": "Yip1A: 81555"
  },
  {
    "caption": "(D, E) Representative confocal micrographs of control (upper panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (lower panels) cells double-stained for Lamp2 (a marker for late endosomes/lysosomes; green) and B. abortus (red) at 24 hr p.i. BCVs co-localized with Lamp2 are indicated by arrowheads. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The percentage of Lamp2-positive BCVs was determined, and is shown in the line graph (E).",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "(D, E) Representative confocal micrographs of control (upper panels), Yip1A-knockdown (middle panels), and IRE1-knockdown (lower panels) cells double-stained for Lamp2 (a marker for late endosomes/lysosomes; green) and B. abortus (red) at 24 hr p.i. BCVs co-localized with Lamp2 are indicated by arrowheads. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The percentage of Lamp2-positive BCVs was determined, and is shown in the line graph (E).",
    "ncbi_link": "IRE1: 2081
Yip1A: 81555"
  },
  {
    "caption": "HeLa cells were infected with B. abortus, and then transfected with each siRNA at 1 hr p.i. (A) Intracellular growth of B. abortus within control (blue bars), Atg9-knockdown (red bars), WIPI1-knockdown (green bars), and DFCP1-knockdown (purple bars) cells. CFUs were counted at the indicated time points after infection. Data are means ± SD from three independent experiments. **: p<0.01.",
    "ncbi_link": "Atg9: 285973///79065
WIPI1: 55062
DFCP1: 53349"
  },
  {
    "caption": "(B, C) Representative confocal micrographs of control (top row), Atg9-knockdown (second row), WIPI1-knockdown (third row), and DFCP1-knockdown (bottom row) cells double-stained for Lamp2 (green) and B. abortus (red) at 24 hr p.i. BCVs co-localized with Lamp2 are indicated by arrowheads. The infected cells are outlined with white dashed lines. Scale bars are 10 μm. The percentage of Lamp2-positive BCVs was determined, and is shown in the line graph (C).",
    "ncbi_link": "Atg9: 285973///79065
WIPI1: 55062
DFCP1: 53349"
  },
  {
    "caption": "(C) Period length decreases with continual differentiation of PSCs into HIOs. Maturation of HIOs into kcHIEs leads to 24-hour rhythms with greater reproducibility. (D) The amplitude of oscillations are significantly higher in kcHIEs/bHIEs compared to HIOs. Bmal1-luc traces in B were generated by plotting the standard deviation of n≥3 biological replicates. ",
    "ncbi_link": "luc: 
Bmal1: 11865"
  },
  {
    "caption": "(A-C) mRNA expression of Bmal1 (black), Rev-erbα (grey) and Per2 (red) in HIOs (A), kcHIEs (B) and bHIEs (C).",
    "ncbi_link": "Bmal1: 11865
Rev-erbα: 217166
Per2: 18627"
  },
  {
    "caption": "(A) Representative images of necrotic cell death (SYTOX orange - red fluorescence) at 2-, 24- and 48-hours post exposure to 10ng/mL TcdB in control Bmal1f/f-EsrCRE enteroids. Scale bar = 250μm. (B) Quantitative analysis of fluorescent intensity from SYTOX orange in control Bmal1f/f-EsrCRE enteroids without tamoxifen treatment. (C) Representative images of necrotic cell death (SYTOX orange) at 2-, 24- and 48-hours post exposure to 10ng/mL TcdB in tamoxifen-treated circadian arrhythmic Bmal1f/f-EsrCRE enteroids. Scale bar = 250μm. (D) Quantitative analysis of fluorescent intensity from SYTOX orange in tamoxifen-treated circadian arrhythmic Bmal1f/f-EsrCRE enteroids. ",
    "ncbi_link": "Bmal1: 11865
CRE: 2777477
Esr: 13982"
  },
  {
    "caption": "(A) Validation of anti-phasic Rac1 expression in mouse (mRac1, red) and human enteroids (hRac1, black) by qRT-PCR. (B) Quantitative analysis of fluorescent intensity from SYTOX orange in Rac1-KD bHIEs. ",
    "ncbi_link": "Rac1: 5879
hRac1: 5879
mRac1: 19353"
  },
  {
    "caption": "(C-D) Quantitative analysis of fluorescent intensity from SYTOX orange in control Rac1 f/f;CAGGCre-ERTM without tamoxifen (C) or Rac1 f/f;CAGGCre-ERTM with tamoxifen-treated (D) enteroids.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rac1: 19353"
  },
  {
    "caption": "A: Single-cell growth of non-dividing b42 cells (ΔmepS/pBAD30-mepS) grown on LB agarose pads as a function of time after addition of arabinose (0.2%) in form of a droplet. Left: Relative increase of volume, mass, surface, and length. Middle: Elongation rate and surface-growth rate. Right: Relative changes of surface-to-mass ratio and width.",
    "ncbi_link": "mepS: 946686"
  },
  {
    "caption": "(A) Immunoblot of total cytoplasmic post-nuclear supernatant (PNS), mitochondrial, microsomal and cytosolic fractions of wild type yeast cells after 18 h expression of EGFP-Abeta42 (A42), EGFP-Abeta40 (A40) and EGFP empty vector (ev) using Abeta-specific antibody (Abeta) 6E10 with long (Long exp.) and short time exposure (Short exp.). Purity of fractions was tested with antibodies against Cyc1 (mitochondria), Sec61 (microsomes) and Pgk1 (cytosol).",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "(B) Cellular ATP content of wild type yeast cells after 42 h expression of EGFP-A42 (A42) or EGFP empty vector (ev). Dot plots show all data points along with the mean (bar) ± s.d.. n = 16 biologically independent cultures. **, p < 0.01. Unpaired, two-tailed t-test.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "(C) Relative protein abundance of EGFP-Abeta42 (A42) versus empty vector (ev) expressing wild type yeast cells. The significant subset of cytosolic heat shock proteins (HSP) detected in a proteomics analysis of isolated mitochondria is depicted. Log2 SILAC ratios of A42/ev of two independent proteome measurements are shown. Dot plots show all data points along with the mean (line). Significance was determined using an outlier test (Significance A, p <0.003).",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "Quantification of cells positive for PI indicating cell death at indicated time points after start of expression of EGFP-A42 (A42) or EGFP empty vector (ev) of wild type (WT) (A) and YDJ1 deleted (Δydj1) cells (B). Mean ± s.d.. n = 5 biologically independent cultures. Comparisons by two-way ANOVA (mixed-design) followed by simple main effects (***, p < 0.001, vs. control).",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "Immunoblot of whole cell extract (Input) and eluate of FLAG-tagged Ydj1. Immunoprecipitation (IP: FLAG) of YDJ1 deletion strain (Δydj1) cells expressing EGFP-A42 (A42) or EGFP empty vector (ev) and co-overexpressing Ydj1-FLAG using Abeta-specific antibody (6E10) and FLAG antibody (FLAG).",
    "ncbi_link": "EGFP: 
FLAG: "
  },
  {
    "caption": "Confocal microscopy of wild type (WT) yeast cells expressing EGFP-A42 (A42) only and co-overexpressing Ydj1-FLAG or with the corresponding vector control after 18 h of expression. Colors indicate fluorescence intensity.",
    "ncbi_link": "FLAG: 
Ydj1: 855661"
  },
  {
    "caption": "Confocal microscopy of wild type (WT) yeast cells expression of EGFP-A42 (A42) and co-overexpressing Ydj1-FLAG after 18 h of expression. Mitochondria were visualized with MitoTracker Red (magenta). See also Fig EV2J, EV1C.",
    "ncbi_link": "EGFP: 
FLAG: "
  },
  {
    "caption": "Immunoblot of total cytoplasmic post-nuclear supernatant (PNS), mitochondrial (Mito.), microsomal (Micro.) and cytosolic (Cyt.) fractions of wild type (WT) and YDJ1 deletion strain (Δydj1) cells after 18 h of expression of EGFP-A42 (A42) and co-overexpressing Ydj1-FLAG or corresponding empty vector controls (ev) using Abeta-specific antibody (Abeta) 6E10 with long (Long exp.) and short time exposure (Short exp.). Tom22-specific antibody is a marker for mitochondria, Sec61 for microsomes and Ssa1 was used to verify cytosolic fraction.",
    "ncbi_link": "EGFP: 
FLAG: 
YDJ1: 855661
ydj1: 855661"
  },
  {
    "caption": "Assay for protein degradation using cycloheximide (CH) to stall protein translation. EGFP fluorescence intensity was measured at two time points (t0 and t2, 2 h after CH administration) and normalized to t0 in wild type (WT) and YDJ1 deletion strain (Δydj1) cells after 18 h of expression of EGFP-A42 (A42) and co-overexpressing Ydj1-FLAG or corresponding empty vector controls (ev). Dot plots show all data points along with the mean (bar) ± s.d.. n = 8 biologically independent cultures. ***, p < 0.001. ANOVA with Tukey's post-hoc. See also Appendix Fig S2D.",
    "ncbi_link": "EGFP: 
FLAG: 
YDJ1: 855661
Δydj1: 855661"
  },
  {
    "caption": "Quantification of the ratio between EGFP-A42 tetramer and monomer in wild type (WT) and YDJ1 deletion strain (Δydj1) expressing EGFP-A42 (J) as well as between WT expressing EGFP-A42 only and co-overexpressing Ydj1-FLAG (K) at indicated time points. Dot plots show all data points along with the mean (bar) ± s.d.. n = 8(J) n=12(K) biologically independent cultures. ***, p < 0.001; **, p < 0.01; *, p < 0.05. ANOVA with Tukey's post-hoc test. See also Appendix Fig S2A-B.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "Quantification of propidium iodide (PI)-staining positive cells indicating cell death at indicated time points of expression of EGFP-A42 (A42) Δydj1 cells with co-expression of DnaJA1-FLAG (DnaJA1) (B) or corresponding empty vector controls (ev) (A). Mean ± SD n = 4-6 biologically independent cultures. Comparisons by two-way ANOVA (mixed design) followed by simple main effects (*P < 0.05, versus control).",
    "ncbi_link": "EGFP: 
FLAG: 
DnaJA1: 3301"
  },
  {
    "caption": "(C)Immunoblot (WB) of whole-cell extract (Input) and eluate of FLAG-tagged DnaJA1 immunoprecipitation (IP: FLAG) of wild-type strain (WT) expressing EGFP-A42 (A42) and co-expressing DnaJA1-FLAG (A1) using Abeta-specific antibody (6E10) and FLAG antibody (FLAG).",
    "ncbi_link": "FLAG: 
DnaJA1: 3301"
  },
  {
    "caption": "Assay for protein degradation using cycloheximide (CH) to stall protein translation. EGFP fluorescence intensity of YDJ1 deletion strain (Δydj1) and wild type (WT) cells expressing EGFP-A42 (A42) only or co-expressing DnaJA1 was measured at two time points (t0 and t2) and normalized to t0. Dot plots show all data points along with the mean (bar) ± s.d.. n = 6 biologically independent cultures. ***, p < 0.001. ANOVA with Tukey's post-hoc test. See also Appendix Fig S2C.",
    "ncbi_link": "DnaJA1: 3301"
  },
  {
    "caption": "Immunoblot (WB) of total cytoplasmic post-nuclear supernatant (PNS), mitochondrial (Mito.), microsomal (Micro.), and cytosolic (Cyt.) fractions of YDJ1-deleted cells (Δydj1) after 18 h expression of EGFP-A42 (A42) only or co-expressing DnaJA1-FLAG (DnaJA1) using Abeta-specific antibody (Abeta) 6E10 with long (Long exp.) and short time (Short exp.) exposure (two sections from one immunoblot). Cox4-specific antibody is a marker for mitochondria, Sec61 for microsomes and Ssa1 was used to verify cytosolic fraction.",
    "ncbi_link": "EGFP: 
FLAG: 
DnaJA1: 3301"
  },
  {
    "caption": "(A) Immunoblot of cytosol-enriched cerebral tissue homogenate (Input) and eluate of Abeta42 or DnaJA1 using Abeta-specific antibody (6E10) and DnaJA1-specific antibody (DnaJA1), respectively, showing optimal and long exposure (Long exp.). Immunoprecipitation using magnetic beads without antibody, DnaJA1 or 6E10 antibody of female (15 months old) wild type (WT) or 3xTg (PS1M146V/APPSwe/tauP301L) mice. Sections showing monomer and low-n oligomers, dodecamer and full-length amyloid precursor protein (APP) are from 1 immunoblot.",
    "ncbi_link": "APP: 351
tau: 4137
PS1: 5663"
  },
  {
    "caption": "(A) Representative confocal microscopy of 10-day-old male fly brains immunostained with Abeta-specific antibody (Abeta) 6E10 (magenta) and reference nuclei staining with DAPI (blue) of Droj2 knockdown flies (Droj2+/-) flies and corresponding isogenic w1118 wild type flies (Droj2+/+) expressing human Abeta42 (UAS-A42).",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(B) Representative confocal and gSTED deconvolved (decon) images of Kenyon cells in 18-day-old male fly brains immunostained with Abeta-specific antibody (Abeta) 6E10 (magenta) and reference nuclei staining with DAPI (blue) of Droj2 knockdown flies (Droj2+/-) flies and corresponding isogenic w1118 wild type flies (Droj2+/+) expressing human Abeta42 (UAS-A42).",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(C-D) Average intensity (C) and total area (D) of Abeta (6E10) signal from confocal images representatively shown in (A) from 12 brains of w1118 wild type (Droj2+/+) and knockdown (Droj2+/-) 10-day-old male flies. Dot plots show all data points along with the mean (bar) ± s.d.. n = 12. *, p < 0.05. Unpaired, two-tailed t-test.",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(E-F) qPCR analysis of Droj2-mRNA levels of 3-6 days old female (E) and male (F) flies expressing human Abeta42 (UAS-A42) of w1118 wild type flies (Droj2+/+) normalized to corresponding isogenic w1118 wild type flies without Abeta42 expression (Droj2+/+ ctrl). Reference gene is Rpl32. Dot plots show all data points along with the mean (line) ± s.d.. n = 3. **, p < 0.01. One sample t-test against 1.",
    "ncbi_link": "Droj2: 41646
Rpl32: 43573"
  },
  {
    "caption": "(G) Immunoprecipitation (IP: 6E10) of w1118 wild type flies (Droj2+/+) using synthetic Abeta42 added to the fly head extract (Input). Abeta-specific antibody 6E10 was used for Abeta42 and DnaJA1-specific antibody for Droj2 immunoblot detection. Showing input, supernatant, supernatant after washing (WS) and eluate.",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(A-B) Survival of female (A) and male (B) w1118 wild type flies (Droj2+/+) and Droj2 knockdown flies (Droj2+/-) with expression of human Abeta42 (UAS-A42) or control flies without expression (ctrl), upon supplementation of sugar (10% sucrose) with 20 mM MnCl2. Survival was determined at indicated time points. n = 6 with 100-120 flies per experiment. The indicated p-value refers to the interaction (int.) term of a Cox Proportional Hazards model comparing Abeta42 toxicity (UAS-A42 vs. ctrl) and Droj2 expression (Droj2+/+ vs. Droj2+/-) as main factors. The following pairwise comparisons of the indicated groups survival were done by Log Rank test (****, p < 0.0001; ns, p > 0.05).",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(C) Aversive associative memory performance 2 min after training of aged (18 days old) male Droj2 knockdown flies (Droj2+/-) and corresponding isogenic w1118 wild type flies (Droj2+/+) both expressing human Abeta42 (UAS-A42) of six independent biological replicates. Dot plots show all data points along with the mean (bar) ± s.d.. n = 6. *, p < 0.05. Unpaired, two-tailed t-test.",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(D) Representative confocal and gSTED deconvolved images of Kenyon cells in 15-day-old male fly brains immunostained with Abeta-specific antibody (Abeta) 6E10 (magenta) and mitochondrial marker ATP5A-specific antibody (ATP5A, green) of Droj2 knockdown flies (Droj2+/-) flies and corresponding isogenic w1118 wild type flies (Droj2+/+) expressing human Abeta42 (UAS-A42).",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "(E-F) Solidity (E) and circularity (F) of ATP5A-stained mitochondria from fly brain gSTED deconvolved images representatively shown in (D) from 8-10 brains of w1118 wild type (Droj2+/+) and knockdown (Droj2+/-) 15-day-old male flies. Dot plots show all data points along with the mean (bar) ± s.d.. n = 8-10. *, p < 0.05. Unpaired, two-tailed t-test.",
    "ncbi_link": "Droj2: 41646"
  },
  {
    "caption": "B  Immunofluorescent staining of cGAS in both WT and G3BP1-/- U937 cells. 3D images were reconstituted with Leica LAS X software. C Quantitative analysis of total cGAS puncta number (left) and volume (right) per cell of (B). n = 51 cells. D Data information: Representative images are shown Scale bars, 5 μm.  Hoechst (blue), nuclear staining. Error bars, mean with s.d , *P < 0.05, **P < 0.01, ****P < 0.0001, two-tailed t-test. NS, non-significant. WT, wild-type.",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "F ELISA analysis of the secreted IFN-β in HT-DNA-treated WT or G3BP1-/- U937  cells. n = 3 biological replicates. Data information: Error bars, mean with s.d , *P < 0.05, **P < 0.01, ****P < 0.0001, two-tailed t-test. NS, non-significant. WT, wild-type. HT-DNA, Herring testes DNA.",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "G  cGAMP production in ISD-treated WT or G3BP1-/- U937 cells were analyzed by  LC-MS/MRM. ND, not detected. n = 3 technical replicates. Data information: Error bars, mean with s.d , *P < 0.05, **P < 0.01, ****P < 0.0001, two-tailed t-test. NS, non-significant. WT, wild-type.  ISD,  interferon stimulatory DNA.",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "G qPCR analysis of  IFNB mRNA levels in WT and G3BP1-/- U937 cells transfected with dsDNA as indicated. n = 3 technical replicates. Data information: Error bars, mean with s.d. , **P < 0.01, two-tailed t-test.",
    "ncbi_link": "G3BP1: 10146
IFNB: 3456"
  },
  {
    "caption": "(A) FAK+/+ and FAK−/− murine SCC cells were lysed and FAK, Ret or Src immunoprecipitated and immunoblotting carried out using anti‐FAK, anti‐Ret, anti‐Src and anti‐actin.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(C) Cells were fixed and stained with anti‐Ret (green) and anti‐FAK (red). Merged images are also shown. Solid arrows indicate co‐localization between Ret and FAK at adhesions, while broken arrows indicate its absence in puncta. Scale bars, 20 μM. DAPI, 4,6‐diamidino‐2‐phenylindole; FAK, focal adhesion kinase; Ret, rearranged during transfection; SCC, squamous cell carcinoma.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "Ret localizes to Src‐positive autophagosomes in FAK‐deficient SCC cells. Cells were fixed and stained with either (A) anti‐Ret (green) and anti‐PY416 Src (red) or (B) anti‐PY416 Src (red) and anti‐LC3B (green). Merged and zoomed images are shown. Solid arrows indicate co‐localization at adhesions, while broken arrows show co‐localization in intracellular puncta.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(C) Cells were transfected with scrambled, Atg5 or Atg7 siRNA, trypsinized and allowed to readhere before immunoblotting with anti‐Atg5, anti‐Atg7 and anti‐actin (right panels). Cells were fixed and stained with anti‐Ret (green), anti‐paxillin (red) and DAPI (blue). Merged images are shown. Solid arrows indicate co‐localization between Ret and paxillin at adhesions, while broken arrows indicate its absence in puncta.",
    "ncbi_link": "Atg5: 11793
Atg7: 74244"
  },
  {
    "caption": "(E) Cells, either untreated or treated with chloroquine for 24 h, were fixed and stained with anti‐Ret (green) and DAPI (blue). Scale bars, 20 μM. DAPI, 4,6‐diamidino‐2‐phenylindole; FAK, focal adhesion kinase; Ret, rearranged during transfection; SCC, squamous cell carcinoma; siRNA, short interfering RNA.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(A) FAK−/− cells stably re‐expressing FAK‐wt, FAK‐Y397F, FAK‐KD or FAK‐Y4F‐Y9F were immunoblotted using anti‐FAK, anti‐FAK Y397, anti‐FAK Y861, anti‐FAK Y925, anti‐Src, anti‐Ret and anti‐actin. FAK and Ret were immunoprecipitated from these cells and then samples were immunoblotted with anti‐Src, anti‐FAK or anti‐Ret.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(C) Quantification of percentage of cells that contained Ret in intracellular puncta is shown. Data are presented as mean±s.d. and the significance calculated using a Student's t‐test (n=3). FAK, focal adhesion kinase; Ret, rearranged during transfection.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(B) Cells were treated with dasatinib, then fixed and stained with anti‐Ret (green), anti‐paxillin (red) and DAPI (blue). Solid arrows indicate co‐localization in adhesions. Quantification of percentage of cells that contained Ret in intracellular puncta is shown. Data are presented as mean±s.d. and the significance calculated using a Student's t‐test (n=3). (C) FAK−/− cells treated with dasatinib were fixed and stained with anti‐Ret (green), anti‐paxillin (red) and DAPI (blue). Solid arrows indicate co‐localization in adhesions, while broken arrows show lack of co‐localization in puncta. Scale bars, 20 μM. Quantification of percentage of cells that contained Ret in intracellular puncta is shown. Data are presented as mean±s.d. and the significance calculated using a Student's t‐test (n=3).",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(D) Lysates from untreated and dasatinib‐treated FAK−/− cells were immunoblotted with anti‐Ret, anti‐PY416 Src, anti‐Src and anti‐actin. Ret was also immunoprecipitated from cells and then immunoblotted using anti‐Src and anti‐Ret. DAPI, 4,6‐diamidino‐2‐phenylindole; FAK, focal adhesion kinase; Ret, rearranged during transfection.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "Endocytic patch formation dynamics in the ydl176wΔ (ipf1Δ) strain. Patch dynamics were examined using time-lapse fluorescence microscopy of wild-type (WT) and ipf1Δ deletion strains carrying reporters for the coat (Sla1-GFP; green), and actin (Sac6-tdTomato; red) modules. Left: Representative kymographs for the WT and ipf1Δ strains. Right: Box plot illustrating the distribution of lifetimes of Sla1-GFP and Sac6-tdTomato patches. Significance was determined using unpaired t-tests. Scale bar: 10 seconds.",
    "ncbi_link": "ipf1: 
ydl176w: 851378"
  },
  {
    "caption": "Penetrance as a function of replicative age. Top: Bar graph showing the fraction of outliers in populations of increasing replicative age (# of divisions) for wild-type (WT), and 5 mutant strains (rrd2Δ, rpl20bΔ, cka2Δ, vac8Δ and vac17Δ). Data are presented as mean of 3 biological replicates +/- SD. Bottom: Box plot with the distribution of cell sizes for the same populations of cells. Whiskers extend to the 5th and 95th percentile.",
    "ncbi_link": "cka2: 854227
rpl20b: 854489
rrd2: 855951
vac17: 850296
vac8: 856702"
  },
  {
    "caption": "Combined effect of replicative age and a vacuole inheritance defect on penetrance. Micrographs of wild-type and vac17Δ cells expressing Vph1-EGFP (green vacuole) and Hta2-mCherry (red nucleus), stained with CF640R WGA (magenta bud scars). Cells with increasing bud-scar staining (replicative age) are shown from left to right. Scale bar: 5 µm.",
    "ncbi_link": "vac17: "
  },
  {
    "caption": "(A) In situ hybridizations for Elp3 transcripts in the developing inner ear. Transcripts are present at E12.5 in a ventro-medial region of the developing cochlear duct (CD) and in the cochleo-vestibular ganglion (CVG). At E16.5, transcripts are present in the spiral ganglion neurons (SGNs) and in the newly formed hair cells (HCs) at the base of the cochlea, where they remain strongly expressed at P1. Scale bar=50µm; inset=25µm. Data information: #IHC; *OHC1; **OHC2; ***OHC3, OC: Organ of Corti.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Validation of Elp3 depletion from the cochlea in Elp3cKO animals. (C) At P1, Elp3 mRNA is absent from Elp3cKO. Scale bars=50µm. In situ hybridizations were repeated 4 times.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Validation of Elp3 depletion from the cochlea in Elp3cKO animals. (D) Western Blots from P1 WT and Elp3cKO cochlear extracts confirm the loss of Elp3 at the protein level (cochleae from 3 different animals are pooled per sample).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(E) Representative ABR recording from P19 WT and Elp3cKO animals reveal an absence of sound-evoked potentials in Elp3cKO animals, indicating that they suffer from severe hearing loss. (F) Elp3cKO animals present increased ABR thresholds (WT/Elp3cKO n=5/3. Unpaired two-tailed t-test, **p=0.0017, t=5.369, DF=6, mean±SD). ",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(A) Toluidine blue stainings of semi-thin sections from P15 WT and Elp3cKO cochleae reveal a drastic reduction in the size of the spiral ganglion due to SGN loss. Scale bar=100µm, OC: Organ of Corti.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(B) Specific labellings of the pre-synaptic marker Ctbp2 (in IHCs) and the post-synaptic marker GluR2/3 (in SGN terminals) indicate a decrease in the number of double-labelled dots in P15 Elp3cKO whole-mounted cochlea compared to WT. The remaining synapses still show coupling of the pre- and post-synaptic markers, suggesting they may be functional. Scale bar=20µm. (C) The mean number of Ctbp2-GluR2/3 double-positive dots in IHCs from the basal region of P15 Elp3cKO cochleae is reduced by 65% compared to control (n=6 animals per genotype; Unpaired two-tailed t-test, ***p<0.001, t=13.48, DF=10, mean±SD). ",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(D) NF-1 and Mafb stainings on P0 cochlear sections indicate that SGN loss occurs before birth in Elp3cKO cochleae. Scale bar=100µm.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(G) The number of apoptotic SGN per section is significantly increased in E13.5 and E14.5 Elp3cKO compared to WT cochleae, suggesting SGNs are properly specified but die during their differentiation process (n=3-4 animals; one-way ANOVA, Tukey's multiple comparisons test; ***p<0.001; **p<0.01; F=23.74; DF=7; mean±SD).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(A) Proteostat staining of WT and Elp3cKO E13.5 cochlear sections reveals the presence of numerous aggresome-like structures in Elp3-deficient SGNs. Scale bar =100µm.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(B) Transmission electron micrographs from E13.5 Elp3cKO SGNs confirm the presence of apoptotic neurons (marked by a red arrowhead) and a large electron dense juxtanuclear structures typical of aggresome (dashed circle). Scale bars =10µm and 2µm (last panel).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(C) Chop and Chac1 transcripts are upregulated in E14 Elp3cKO compared to WT cochleae (n=8/6 for WT/KO; unpaired t-test two-tailed; p=0.0001/0.0015/0.0010; t=9.535/4.090/4.307; DF=12/12/12 for Elp3, Chop and Chac1 respectively; mean±SEM presented) indicating that the pro-apoptotic arm of the unfolded protein response (UPR) is activated in Elp3-deficient SGNs.",
    "ncbi_link": "Chac1: 69065
Chop: 13198
Elp3: 74195"
  },
  {
    "caption": "(D-E) Proteostat staining of whole-mounted P0 organs of Corti reveal the presence of aggregates in HCs upon loss of Elp3. Orthogonal slices (Orthog) reveal aggregated proteins localize at the apical surface of Elp3cKO HCs. Scale bars =5µm. #IHC; *OHC1; **OHC2; ***OHC3.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(F) Protein extracts from P1 cochleae show increased levels of polyubiquitinated conjugates upon loss of Elp3, confirming proteostasis disruption.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(G) The levels of Chop and Chac1 transcripts are unaffected by Elp3 depletion in P0 organs of Corti (n=3 animals per genotype; unpaired t-test two-tailed; p=0.0003/0.4296/0.056; t=11.62/0.8778/2.662; DF=4/4/4 for Elp3, Chop and Chac1 respectively; mean±SEM presented) suggesting that proteostasis disruption in Elp3cKO HCs is not sufficient to induce UPR-mediated apoptosis.",
    "ncbi_link": "Chac1: 69065
Chop: 13198
Elp3: 74195"
  },
  {
    "caption": "(A) Scanning electron micrographs of cochlear tissue from P19 animals indicate no HC loss in the absence of Elp3 but illustrate some defects of polarity, as misaligned HCs and dysmorphic stereociliary bundles are visible (red arrows and white arrowheads, respectively). Scale bars=5µ",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(B) Surface view of P1 actin-stained organ of Corti confirms defective establishment of polarity in Elp3cKO as numerous stereociliary bundles are misaligned along the medio-lateral axis (M-L) or misshaped. Scale bars=5µm. Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(C) Elp3cKOs exhibit a broader distribution of hair cell orientation. The angles of deviation between the stereociliary bundle and the medio-lateral axis are plotted in rose diagrams, for each OHC row. Whereas the majority of WT bundles are pointing to the most lateral region of the tissue (within a range of 10°), many Elp3cKO bundles of the two last rows of OHCs present increased angles of deviation (WT/Elp3cKO OHC1: n=99/99, p>0.1, DF=99; OHC2: n=99/100, p<0.001, DF=99; OHC3: n=99/98, p<0.001, DF=98; pooled data from 6 animals per genotype; Watson U2 test). Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Elp3cKOs HCs harbour a flatter stereociliary bundle that is centrally shifted. (D) Scanning electron micrographs of HCs from P1 WT and Elp3cKO cochleae (scale bar=2µm) illustrating the misshaped stereociliary bundles and the shorter kinocilium (false coloured in pink) of Elp3cKO HCs. Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Elp3cKOs HCs harbour a flatter stereociliary bundle that is centrally shifted. (E) Graph presents the mean angle of HC bundle (n=6 animals; one-way ANOVA, Tukey's multiple comparisons test; ***p<0.001, F=13.69, DF=7; mean±SD).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Elp3cKOs HCs harbour a flatter stereociliary bundle that is centrally shifted. (F) Elp3cKO HCs possess a significantly larger bare zone (WT/KO IHC: n= 23/24 cells; OHC1: n=27/27; OHC2: n=27/29; OHC3: n=30/29; cumulative data collected from 3 animals per genotype; One-way ANOVA, Tukey's multiple comparisons test; ***p<0.001, *p<0.05 F=16.72, DF=7; mean±SD).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Elp3cKOs HCs harbour a flatter stereociliary bundle that is centrally shifted. (G) Elp3cKO HCs possess a significantly smaller medial zone (WT/KO IHC: n= 23/24 cells; OHC1: n=27/27; OHC2: n=27/29; OHC3: n=27/29; cumulative data collected from 3 animals per genotype; One-way ANOVA, Tukey's multiple comparisons test; ***p<0.001, *p<0.05, F=63.3, DF=7; mean±SD).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(H) Kinocilia are shorter in Elp3cKO HCs (WT/KO IHC: n=15/15; OHC1: n=30/32; OHC3: n=31/30; OHC3: n=27/30; data collected from 3 animals per genotype; One-way ANOVA, Tukey's multiple comparisons test, ***p<0.001, **p<0.01F=19.6, DF=7; mean±SD).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(I) High magnification of representative HCs from P1 WT and Elp3cKO cochlea stained for F-actin and gamma-tubulin (white). The basal body of kinocilia is shifted centrally at the apical surface of Elp3cKO HCs. Scale bars=2µm. Polar plotting of kinocilium basal body position for each row of HCs of WT and Elp3cKO (WT/KO IHC: n= 42/32; OHC1: n= 47/48; OHC2: n= 47/45; OHC3: n= 44/44; cumulative data collected from 3 animals per genotype). Cellular orientations were tested using Watson U2 test (p<0.001 between WT/Elp3cKO, for all HC rows) and the mean vector lengths, determined from the cell centre to the basal body, were compared using t-tests (p<0.001 between WT/Elp3cKO, for all HC rows).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "The localization of apical polarity proteins is affected by Elp3 loss. Surface views of mid-basal turn of P1 cochleae from WT or Elp3cKO mice stained with LGN (J) and F-actin. The enrichment of these apical polarity regulators at the lateral edges of HCs is disrupted in Elp3cKO HCs. Scale bars=5µm (upper panels) and 2µm (lower panels). Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "The localization of apical polarity proteins is affected by Elp3 loss. Surface views of mid-basal turn of P1 cochleae from WT or Elp3cKO mice stained with Gαi3 (K) and F-actin. The enrichment of these apical polarity regulators at the lateral edges of HCs is disrupted in Elp3cKO HCs. Scale bars=5µm (upper panels) and 2µm (lower panels). Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "The localization of apical polarity proteins is affected by Elp3 loss. Surface views of mid-basal turn of P1 cochleae from WT or Elp3cKO mice stained with aPKC (L) and F-actin. The enrichment of these apical polarity regulators at the medial (L) edges of HCs is disrupted in Elp3cKO HCs. Scale bars=5µm (upper panels) and 2µm (lower panels). Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(A-B) Polarized enrichment of LGN at the cortices of dividing HEK293T cells is disrupted upon Elp3 or Alkbh8 knockdown. (A) HEK293T cells transfected with siRNAs for Elp3, Alkbh8 or control and immunolabelled with LGN, acetylated alpha-tubulin and DAPI. Scale bar=5µm. (B) The mean fluorescence intensity profile of LGN across the radii perpendicular to division in HEK293T cells was quantified (siRNA Control/Elp3/Alkbh8: n=27/30/27; pooled from 3 independent experiments; mean±SEM).",
    "ncbi_link": "Alkbh8: 91801
Elp3: 55140"
  },
  {
    "caption": "(C-D) The length of the primary cilium is reduced in non-dividing HEK293T cells upon Elp3 or Albh8 knockdown. (C) Control, Elp3 or Alkbh8 siRNA-treated HEK293T cells were immunolabelled for basal body marker ALMS1, axoneme marker Arl13b and DAPI. Scale bar=5µm. (D) Primary cilium length of non-dividing HEK293T was measured and pooled data were plotted (siRNA Control/Elp3/Alkbh8: n=94/81/90; data collected from 3 independent experiments; One-way ANOVA, Tukey's multiple comparisons test, ***p<0.001, F=21.46, DF=4; minimum, first quartile, median, third quartile and maximum presented).",
    "ncbi_link": "Albh8: 91801
Alkbh8: 91801
Elp3: 55140"
  },
  {
    "caption": "(E-F) Elp3 knockdown increases the amount of polyubiquitinated conjugates in HEK293T cells (n=3; One-way ANOVA, Tukey's multiple comparisons test, **p<0.01, *p<0.05, F=16.51, DF=2; mean±SD).",
    "ncbi_link": "Elp3: 55140"
  },
  {
    "caption": "(G) Increased formation of aggresome-like structures in Elp3- or Alkbh8-depleted HEK293T. Aggresomes (red); DAPI (blue). Enlarged images depict examples of non-dividing (left) and dividing (right) cells. Scale bar=10µm.",
    "ncbi_link": "Alkbh8: 91801
Elp3: 55140"
  },
  {
    "caption": "LGN and Gαi3 protein levels are not affected by Elp3 loss. (A) Western blots with total lysates from control and Elp3 siRNA-treated HEK293T cells and corresponding quantifications of normalized LGN, Gαi3 and Elp3 levels (n=6 from 2 independent cultures; Unpaired two-tailed t-test, LGN: p=0.749, t=0.328, DF=10, Gαi3: p=0.275, t=1.155, DF=10, Elp3: ***p=0.0003, t=5.438, DF=10, mean±SEM).",
    "ncbi_link": "Elp3: 55140"
  },
  {
    "caption": "LGN and Gαi3 protein levels are not affected by Elp3 loss. (B) Western blots on P0 WT and Elp3cKO cochlear extracts and corresponding quantifications of normalized LGN and Gαi3 levels (n=3, each lysate obtained from cochleae pooled from 2 animals; Unpaired two-tailed t-test, LGN: p=0.586, t=0.591, DF=4, Gαi3: p=0.963, t=0.0491, DF=4, mean±SEM).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(C) Mislocalized LGN and Gαi3 are not found in protein aggregates formed upon Elp3 depletion. HEK293T transfected with Elp3 siRNA were co-stained for aggresomes, Dapi and LGN or Gαi3. Scale bar=5µm.",
    "ncbi_link": "Elp3: 55140"
  },
  {
    "caption": "Microtubular transport speed is reduced by the presence of aggresome-like structures in HEK293T cells and is improved upon 4-PBA treatment. The mean velocity of lysosomes was measured on time-lapse recordings of HEK293T cells labelled with LysoTracker®. (E): siCtl/+4PBA n=622/677; siElp3/+4PBA n=674/577; siAlkbh8/+4PBA n=460/484, pooled from 4 experiments, ***p<0.001. All data analysed with Kruskal-Wallis ANOVA, Dunn's multiple comparisons test. Box/whisker plots depict minimum, first quartile, median, third quartile, and maximum.",
    "ncbi_link": "Alkbh8: 91801
Elp3: 55140"
  },
  {
    "caption": "Microtubular transport speed is reduced by the presence of aggresome-like structures in cultured HCs, and is improved upon 4-PBA treatment. The mean velocity of lysosomes was measured on time-lapse recordings of HCs, at the level of their apical surface labelled with LysoTracker®. (G): WT/WT+4PBA/Elp3cKO/Elp3cKO+4PBA n=732/763/730/738, pooled from 4 OCs per condition, ***p<0.001, **p<0.01. All data analysed with Kruskal-Wallis ANOVA, Dunn's multiple comparisons test. Box/whisker plots depict minimum, first quartile, median, third quartile, and maximum.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "In vivo administration of 4-PBA improves LGN localization and kinocilium position in Elp3cKO cochlear HCs. Pregnant mice were treated daily with saline or 4-PBA from E13.5 and the cochleae of WT and Elp3cKO embryos were analysed by immunostainings at E17.5. (D) The arc of lateral LGN enrichment remains in many Elp3cKO HCs after 4PBA administration. Scale bars=5µm; magnified views=2µm. Data information: #IHC; *OHC1; **OHC2; ***OHC3",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "In vivo administration of 4-PBA improves LGN localization and kinocilium position in Elp3cKO cochlear HCs. Pregnant mice were treated daily with saline or 4-PBA from E13.5 and the cochleae of WT and Elp3cKO embryos were analysed by immunostainings at E17.5. (E) Acetylated alpha-tubulin immunostaining showing kinocilium position in WT or Elp3cKO OCs in the presence or absence of 4-PBA (yellow arrowheads = base of kinocilium; scale bar=2µm).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "In vivo administration of 4-PBA improves LGN localization and kinocilium position in Elp3cKO cochlear HCs. Pregnant mice were treated daily with saline or 4-PBA from E13.5 and the cochleae of WT and Elp3cKO embryos were analysed by immunostainings at E17.5. (F) Kinocilium position plotted as a fraction of HC diameter for each HC row (WT/WT+4PBA/Elp3cKO/Elp3cKO+4PBA IHC: n=35/31/35/36, p=0.6812, F=4.510, DF=3; OHC1: n=36/32/37/40, ***p<0.001, **p<0.01, F=27.60, DF=3; OHC2: n=35/33/38/42, ***p<0.001, F=76.62, DF=3; OHC3: n=36/32/38/39, ***p<0.001, *p<0.05, F=27.86, DF=3; pooled from 3 animals per condition; mean±SD; One-way ANOVA with Tukey's multiple comparisons test).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "(A) Representative images (and details from boxed regions) of WT MEF  cells transfected with   YFPParkin (green) and treated with FCCP (10 μM) to induce mitophagy. Cells were immunostained with anti-Tom20 (magenta) to reveal the mitochondrial network. Each row represents one stage in the process of  mitophagy that has been used to score the progression of mitophagy at different  time-points for the different conditions tested (the specific time-point of each example is indicated in the  image). From top to bottom: i) \"Diffuse Parkin\" defines cells in where  Parkin expression is homogenously distributed throughout the cytoplasm (quantified in B). ii) Soon after  mitochondrial  damage  Parkin appears enriched in small \"puncta\" throughout the cytoplasm localizing within isolated mitochondria (quantified in C). iii) Later in the process these puncta structures aggregate in bigger structures accumulating in perinuclear  regions (quantified in D). iv) The process of Parkin translocation eventually affects all the mitochondrial population and usually collapses in few large structures possibly forming part of big autolysosomes in the perinuclear region (quantified in D). Scoring was performed from 3 independent experiments (n=3; one way ANOVA with Dunnett post test). Error bars represent s.e.m. Significance: *p<0.05 and **p<0.01",
    "ncbi_link": "YFP: 
Parkin: 5071"
  },
  {
    "caption": "(F) Representative images (and details from boxed regions) of WT MEFs cells transfected with GFPPINK1 (green) and treated with FCCP (10 μM) to induce  mitophagy. Cells were immunostained  with anti-Tom20 (magenta) to reveal the mitochondrial  network. Each row represents one of the three categories of  GFP signal used to describe  PINK1 translocation to  mitochondria after mitochondrial damage (cytoplasmic, intermediate and mitochondrial). The scoring of these categories was used to describe PINK1 translocation to mitochondria in WT and  MiroDKO cells at different time-points shortly after mitochondrial insult (G). Data collected from 3 independent experiments (n=3). Error bars represent s.e.m. Significance: *p<0.05 and **p<0.01 ",
    "ncbi_link": "GFP: 
PINK1: 65018
Miro: 214952///59040"
  },
  {
    "caption": "B) Representative  images showing full length control and selected Miro1 lysine mutants (Miro15R, Miro1allR and Miro1R572K) expressing in MiroDKO MEF  cells. All constructs (myc-tag, green) localise to mitochondria (Tom20, red).",
    "ncbi_link": "Miro1: 55288
Miro: 214952///59040"
  },
  {
    "caption": "C) Immunoblot showing efficient expression of  Miro1 lysine mutants in   FlagParkin expressing SH-SY5Y cells.",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "D) Ubiquitination assay showing that Miro1 lysine mutants have reduced ubiquitination upon  FCCP treatment (1h, 10 μM) in FlagParkin overexpressing SH-SY5Y. The effect is quantified in (E) (n=4 independent experiments for Miro1WT and Miro15R and n=3 for  Miro1allR and Miro1R572K, ANOVA with Sidak's post hoc test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001.",
    "ncbi_link": "Flag: 
Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "F) Representative western blot showing a degradation assay in FlagParkin overexpressing SH-SY5Y  cells transfected with  Miro1WT, Miro15R or Miro1allR constructs and treated with FCCP  (10 μM) for 3 or 6 hours. Quantification of Miro1 levels (G) the matrix protein PDH E1α in (H) and  Parkin levels (I) (n=4 independent experiments; ANOVA with Sidak's post hoc test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001. ",
    "ncbi_link": "Flag: 
Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "(A) Representative images at 3 hours of FCCP treatment (10 μM) of YFPParkin  (green) expressing  MiroDKO cells co-transfected with the specified myc-tagged versions of Miro1 (cyan). Tom20 (red) was used to reveal the mitochondrial network. A detail of YFPParkin translocation onto the mitochondrial  network is also shown for each condition.",
    "ncbi_link": "myc: 
YFP: 
Parkin: 5071
Miro: 214952///59040"
  },
  {
    "caption": "(B and C) Quantification of the  fraction of cells showing advanced stages of the mitophagic process  (cells showing mitochondrial aggregation due to advanced  Parkin translocation or the complete translocation of  Parkin onto all the mitochondrial  network) at 1 hour (B) or 3 hours (C) after  FCCP treatment (data collected from at least 3 independent experiments: WT n=7,  MiroDKO n=8, +mycMiro1WT=7, mycMiro15R=3, mycMiro1allR=3; mycMiro2=3; one way ANOVA with Dunnett post test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001",
    "ncbi_link": "myc: 
Miro1: 55288
Miro2: 214952
Miro: 214952///59040"
  },
  {
    "caption": "D) Western blots and quantification of  Miro1 degradation in MiroDKO cells co-expressing YFPParkin and the indicated  myc-tagged Miro1 constructs and treated with  FCCP (10 μM) for the indicated times  (n=3 different experiments; 2-way-ANOVA with Dunnett post test; comparisons between Miro1WT and Miro1allR are represented with yellow asteriscs, comparisons between Miro1WT and Miro15R are represented in green and comparisons between Miro15R and Miro1allR are represented in black).",
    "ncbi_link": "myc: 
YFP: 
Parkin: 5071
Miro1: 55288
Miro: 214952///59040"
  },
  {
    "caption": "E). Representative  images at 24 hours of FCCP treatment (10 μM) of YFPParkin (green) expressing MiroDKO cells co-transfected with the specified myc-tagged versions of Miro1 (cyan). Tom20 (red) was used to reveal the  mitochondrial  network. Expression of both ubiquitin mutants (Miro15R and Miro1allR - arrowheads) protects from the mitophagic clearance of  mitochondria  (arrows) after damage. (F) Quantification of the fraction  of cells showing the complete loss of  Tom20 signal of mitochondria  after 24 hours of FCCP  treatment (data collected from at least 3 independent experiments: MiroDKO n=8, mycMiro1WT=7,   mycMiro15R=3, mycMiro1allR=3; one way ANOVA with Dunnett post test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001 ",
    "ncbi_link": "myc: 
YFP: 
Parkin: 5071
Miro1: 55288
Miro: 214952///59040"
  },
  {
    "caption": "(A) Representative  confocal images of the soma of WT and Miro1KO cortical neurons expressing YFPParkin and MtDsRed  after valinomycin treatment at the indicated  time points (scale bars = 5 µm).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(B) Airyscan confocal images  of Parkin recruitment after 5 hours of valinomycin treatment in WT and Miro1KO neuronal  processes (scale bars = 2.5 µm).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(C)  Fluorescent linescans of YFPParkin and MtDsRed signal in WT and Miro1KO neurons after 5 hours of valinomycin treatment (lines shown in A).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(D) Quantification of Parkin recruitment to mitochondria (YFPParkin signal overlapping MtDsRed  signal - intensity-adjusted and normalised to t=0) in WT and Miro1KO neurons following valinomycin treatment (n=15 cells all conditions per genotype over 3 neuronal preparations; two-way ANOVA). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(E) Quantification of mitochondrial   occupancy (area of MtDsRed signal in soma / entire area of soma) in the somas of WT and Miro1KO neurons following  valinomycin treatment (n=15 cells all conditions per genotype over 3 neuronal preparations; two-way ANOVA).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(F) Quantification of mitochondrial   clearance in  somas of WT and Miro1KO neurons between 2 and 5 hours of valinomycin treatment (n=15 cells all conditions per genotype over 3  neuronal preparations; Unpaired t-test).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(G) Representative confocal images of WT,  Miro1KO and PINK1KO cortical neurons immunostained  with MAP2  (cyan) and s65-phospho-ubiquitin (green) after valinomycin treatment (Scale bars = 20µm). (H) Quantification of s65-phospho-ubiquitin signal  intensity within  MAP2 signal (normalised to MAP2 area and t=0) in Miro1WT, Miro1KO and PINK1KO neurons following valinomycin treatment n= 3, 4 and 3  embryos from WT, Miro1KO and PINK1KO embryos, respectively (6 ROIs per condition; two-way ANOVA). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001",
    "ncbi_link": "PINK1: 68943
Miro1: 59040"
  },
  {
    "caption": "(I) Representative  confocal images of the  soma  of Miro1KO cortical neurons expressing Miro1WT and mutant forms of Miro1,   YFPParkin and MtDsRed without valinomycin treatment (Scale bars = 10 µm). Quantification of parkin colocalization with MtDsRed (YFPParkin signal overlapping MtDsRed  signal - intensity-adjusted) in the soma of Miro1KO and PINK1KO cortical neurons (n=12 cells all conditions per genotype over 3 neuronal preparations; one-way ANOVA). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001",
    "ncbi_link": "PINK1: 68943
Miro1: 59040"
  },
  {
    "caption": "(J) Representative confocal images of the soma of  Miro1KO cortical neurons expressing WT and mutant forms of  Miro1, YFPParkin and  MtDsRed after 5 hours of valinomycin treatment (Scale bars = 10 µm). Quantification of  Parkin recruitment to mitochondria (Normalised to t=0) in  Miro1KO and PINK1KO cortical neurons following  valinomycin treatment (n=12 cells all conditions per genotype over 3 neuronal preparations, two-way ANOVA). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001 ",
    "ncbi_link": "PINK1: 68943
Miro1: 59040"
  },
  {
    "caption": "(A) Representative  blots of 4 and 12 months old hippocampal lysates from control, Miro1CKO and Miro2KO. B) Quantification of protein levels in 4 month lysates and 12 month  lysates (n=3 animals / genotype at 4 months and n=4 animals / genotype at 12 months; one-way ANOVA with post-hoc Dunnett's test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "C) Representative images of  hippocampal regions from control and Miro1CKO crossed with MitoDendra animals.",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(D) Details from cortical  regions of control, Miro1CKO and Miro2KO animals at 12 months of age showing large mitochondrial  structures occurring only in the case of Miro1CKO animals.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "(E) Electron microcopy images of control and  Miro1CKO brains showing the ultrastructure of the mitochondrial compartment. The mitochondrial units in Miro1CKO cells are enlarged and show altered cristae structure at 4 months of age. This process is progressive as mitochondrial  structures appear larger and with reduced intramitochondrial complexity at 12 months of  age.",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "Representative images (F) and quantification (G) of  Mfn1 and  Mfn2 staining in cortical  slices from 12 month WT and Miro1CKO mice  (n=4 animals / genotype; student's t-test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001. ",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(A) Representative  western blot images of  brain lysates from 12-month WT, Miro1CKO and Miro2KO mice immunoblotted  with the antibodies stated. (B) Quantification of  eIF2α and P-eIF2α band intensity (normalised to actin band  intensity) from 12-month WT, Miro1CKO and Miro2KO brain lysates. Phosphorylation of eIF2α  is defined as P-eIF2α/eIF2α (n=4 mice per genotype, unpaired t-test). Error bars represent s.e.m. Significance: *p<0.05, **p<0.01 and ***p<0.001.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "(C) Representative confocal images of cortical regions of 12-month mitoDendra-crossed WT and Miro1CKO mice stained with MAP2 and P-eIF2α. (D) Quantification of P-eIF2α signal intensity from cortical regions of 12-month  mitoDendra-crossed WT and Miro1CKO mice  (n=4 mice per genotype; unpaired t-test).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(E) Representative confocal images (63x) of cortical regions of 12-month mitoDendra -crossed WT and Miro1CKO mice stained with MAP2 and P-eIF2α. Arrows indicate the presence of megamitochondria (>2.5 µm2), stars indicate neuronal somas without  megamitochondria.",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(F) Example zoom images of  neuronal somas with and without megamitochondria from cortical regions of 12-month  mitoDendra -crossed Miro1CKO mice stained with P-eIF2α. (G) Quantification P-eIF2α signal intensity (a.u.) from  neuronal somas with and without megamitochondria from cortical regions of 12-month mitoDendra-crossed Miro1CKO (n=16 sections from 4 mice; paired t-test).",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "(N) The hepatic mRNA levels of Il-6, Il-1β, Tnf-α and Mcp-1 involved in necroptosis at normal or necroptotic area from mice injected with PBS or rAAV in (H). n = 7 - 8 biological replicates.",
    "ncbi_link": "Mcp-1: 20296
Il-1β: 16176
Il-6: 16193
Tnf-α: 21926"
  },
  {
    "caption": "(L) The hepatic mRNA levels of Il-6, Il-1β, Tnf-α and Mcp-1 involved in necroptosis at normal or necroptotic area from mice in (E).",
    "ncbi_link": "Mcp-1: 20296
Il-1β: 16176
Il-6: 16193
Tnf-α: 21926"
  },
  {
    "caption": "Body weight (D) of db/db mice after a single injection of rAAV-si-NC/Cyp4a14/Pebp1/Tat for 2 months. n = 10 - 12. rAAV-si-NC was packaged as indicated in Fig. 1A",
    "ncbi_link": "Cyp4a14: 13119
Pebp1: 23980
Tat: 234724"
  },
  {
    "caption": "Two months after a single injection of rAAV-si-Pebp1, HFD-induced hyperglycemic and obese mice showed blood glucose levels (C) with the mice injected with rAAV-si-NC. n = 10 - 11. (D-E) Serum ALT (D) and AST (E) activities from mice in (B). The colored dots indicate the mice with high ALT or AST activity, and the same color dot in (D) and (E) indicates the same mouse.",
    "ncbi_link": "Pebp1: 23980"
  },
  {
    "caption": "(A) The effect of si-Pebp1 in primary mouse macrophages. n = 3. (B) Knockdown of Pebp1 markedly blocked the increase of some key inflammatory factors in mouse macrophages treated with poly(I:C). n = 6.",
    "ncbi_link": "Pebp1: 23980"
  },
  {
    "caption": "Knockdown of Pebp1 markedly blocked the loss of cell membrane integrity (C, n = 6 in duplicate or triplicate.) of mouse macrophages induced by poly(I:C) and z-VAD-fmk.",
    "ncbi_link": "Pebp1: 23980"
  },
  {
    "caption": "(E) Knockdown of Pebp1 attenuated the increase of p-Tbk1 level induced by poly(I:C). n = 3 biological replicates.",
    "ncbi_link": "Pebp1: 23980"
  },
  {
    "caption": "Knockdown of Tbk1 markedly blocked the loss of cell membrane integrity (H of mouse macrophages induced by poly(I:C) and z-VAD-fmk.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "After a single injection of rAAV-si-Tbk1 for 11 weeks, the db/db mice showed blood glucose levels (M) with the mice injected with rAAV-si-NC. n = 11. (N-O) Serum ALT (N) and AST (O) activities of mice in (K).",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "F RT-qPCR showing relative levels of miR-122 and indicated mRNAs in GA of indicated groups of mice. Data were normalized to U6 (for miR-122) or Ppib (for all mRNAs) and compared to control group receiving PBS (one-way ANOVA, n=4 or 5 mice per group). Data information: In bar graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.",
    "ncbi_link": "miR-122: 387231
Ppib: 19035
U6: 19864"
  },
  {
    "caption": "C Responsiveness of the reporters to miR-122 mimic in transfected C2C12 (t-test, n=3 biological replicates). Data information: In bar graph, values are shown as mean ± SD. **P<0.01, ns: not significant.",
    "ncbi_link": "miR-122: RF00684"
  },
  {
    "caption": "A Western blot showing levels of indicated proteins in C2C12 treated with indicated EVs, or transfected as indicated with miR-122 mimic or TP53 expression plasmid carrying silent mutation of the miR-122 binding site. Data information: Western blot signals are quantified and normalized to Gapdh.",
    "ncbi_link": "miR-122: RF00684
TP53: 7157"
  },
  {
    "caption": "D RT-qPCR indicated mRNAs (D) in GA of tumor-free and tumor-bearing mice. Data were normalized to Ppib (for all mRNAs) and compared to the tumor-free group (one-way ANOVA, n=4 or 5 mice per group). Data information: In bar graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.",
    "ncbi_link": "Ppib: 19035"
  },
  {
    "caption": "C RT-qPCR showing indicated mRNAs in GA of indicated groups of mice. Data were normalized to Ppib and compared to control group receiving PBS (one-way ANOVA, n=4 mice per group). Data information: In bar graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ns: not significant.",
    "ncbi_link": "Ppib: 19035"
  },
  {
    "caption": "AAV8-TP53 virus or AAV8-eGFP control virus were injected into GA of both sides twice during the entire experiments, first immediately following implantation of MDA-MB-231 cells into the mammary fat pad, and then one month later. Muscles were collected at 6 weeks after tumor implantation. A Western blot showing indicated protein levels in the GA. Western blot signals are quantified and normalized to Gapdh.",
    "ncbi_link": "eGFP: 
TP53: 7157"
  },
  {
    "caption": "AAV8-TP53 virus or AAV8-eGFP control virus were injected into GA of both sides twice during the entire experiments, first immediately following implantation of MDA-MB-231 cells into the mammary fat pad, and then one month later. Muscles were collected at 6 weeks after tumor implantation. C Relative mtDNA/nDNA ratio in GA determined by PCR (two-tailed Student's t-test, n=8 mice per group). Data information: In all bar and line graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.",
    "ncbi_link": "eGFP: 
TP53: 7157"
  },
  {
    "caption": "AAV8-TP53 virus or AAV8-eGFP control virus were injected into GA of both sides twice during the entire experiments, first immediately following implantation of MDA-MB-231 cells into the mammary fat pad, and then one month later. Muscles were collected at 6 weeks after tumor implantation. D Representative TEM images showing SS and IMF mitochondria and their quantification in GA (two-tailed Student's t-test, n=3 mice per group for the left subpanel and n=166 or 181 mitochondria analyzed per group for the right subpanel). Scale bar: 1 µm. Yellow bars: depths of SS mitochondrial areas; arrows: IMF mitochondrial area. Data information: In all bar and line graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.",
    "ncbi_link": "eGFP: 
TP53: 7157"
  },
  {
    "caption": "AAV8-TP53 virus or AAV8-eGFP control virus were injected into GA of both sides twice during the entire experiments, first immediately following implantation of MDA-MB-231 cells into the mammary fat pad, and then one month later. Muscles were collected at 6 weeks after tumor implantation. E ROS levels in GA from indicated groups of mice. Quantified DHE signals were normalized to DAPI signals on the same section and used in analysis (two-tailed Student's t-test, n=4 mice per group). Scale bar: 50 µm. Data information: In all bar and line graphs, values are shown as mean ± SD. The boxes in the box-and-whiskers plots show the median (center line) and the quartile range (25-75%), and the whiskers extend from the quartile to the minimum and maximum values. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.",
    "ncbi_link": "eGFP: 
TP53: 7157"
  },
  {
    "caption": "a, Polychromasia (Wright-Giemsa stain, indicated by arrows) and increased reticulocytes (brilliant cresyl blue stain) revealed by staining blood smears from 6-week-old wild-type (WT) or Nix-/- mice (scale bar, 20 µm).",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "c, The relative luminescence units (RLU) of caspase activities in cultured RBCs and the suppression of annexin V staining in Nix-/- RBCs after 12-h culture in the presence of qVD-oph or solvent control (DMSO) (n = 3).",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "e, Mean fluorescent intensity (MFI) of ROS staining in RBCs after in vitro culture, and caspase activities in Nix-/- RBCs after 24 h culture with solvent control, ROS scavengers or qVD-oph (n = 3). BHT, butylated hydroxytoluene; CAT, catalase; TEM, tempol.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "f, Haematoxylin and eosin (HE) staining of spleen sections of 9-week-old wild-type and Nix-/- mice. Arrows denote iron deposits within macrophagecytoplasm. Iron deposits were also stained with Prussian blue, followed by counterstain with nuclear-fast red. Scale bar, 20 µm.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "g, Real-time RT-PCR of erythropoietin (Epo) (n = 12). For all relevant panels, statistical significance of the data (mean ± s.e.m.) is: *P < 0.05; **P < 0.01; ***P < 0.001.",
    "ncbi_link": "erythropoietin: 13856"
  },
  {
    "caption": "c, CD71+Ter119+ reticulocytes sorted at day 3 after PHZ treatment were stained for LC3 and COX IV and analysed by deconvolution microscopy. Scale bar, 5 µm. The Pearson coefficiency for LC3 and COX IV co-localization at day 0 (mean ± s.e.m.) is: wild type, 0.81 ± 0.001; Nix-/-, 0.44 ± 0.036 (n = 35, P = 0.0006).",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "a, Ter119+CD71+ reticulocytes were sorted from the peripheral blood of wild-type and Nix-/- mice at day 6 after PHZ treatment. The cells were cultured for in vitro maturation in the presence of 10 µM FCCP or 1 µM ABT-737, followed by staining with Mitotracker deep red and phycoerythrin-conjugated anti-Ter119.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "C Quantification of total numbers of generated cell types (BrdU+; rNSCs, IPCs  + neuroblasts, astrocytes) per area in the DGs  of 8 week-, 14 month-, and 21 month-old hGFAPeGFP animals. rNSCs: *** p = 0.00076, ** p = 0.0014; IPCs/neuroblasts  **** p < 0.0001; astrocytes: *** p = 0.0008; * p = 0.0403; one-way ANOVA with Tukey's post hoc test. D Quantification of the percentages of generated cell types out of all generated cells (rNSCs, IPCs  + neuroblasts, astrocytes) in the DG  of 8 week-, 14 month-, and 21 month-old animals. rNSCs: not significant; IPCs/neuroblasts  **** p < 0.0001, *** p = 0.0001; astrocytes: ** p < 0.0019, **** p < 0.0001; one-way ANOVA with Tukey's post hoc test. Data information: All data are represented as mean ± SEM; number of experimental animals (indicated by red dots): (C,D) n = 5 in 8 week-old mice, n = 6 in 14 month-old mice, n = 5 in 21 month-old mice",
    "ncbi_link": "eGFP: 
GFAP: 2670"
  },
  {
    "caption": "G Confocal  images of 8 week- and 14 month-old NestinCreERT2; GFP  animals, which received tamoxifen  for five days (10 times, every 12 h) and were killed 12 days after the last tamoxifen  shot. The majority of recombined cells were rNSCs  [SOX2+ cell nuclei  (cyan) residing in the SGZ  with a NESTIN+ radial process (white)] and IPCs/neuroblasts [SOX2+ (cyan) nuclei located  to the SGZ, DCX+ cells (magenta) in the SGZ  and GZ, respectively], and only very few astrocytes  [SOX2+ cells (cyan) in the hilus, GZ, and ML] were generated by initially recombined rNSCs. H Quantification of total numbers of recombined (GFP+) rNSCs, IPCs/neuroblasts, astrocytes  per area in the DGs of 8 week- and 14 month-old animals. rNSCs: * p = 0.0460; IPCs/neuroblasts: **** < 0.0001; astrocytes: not significant; unpaired t-test. Data information: All data are represented as mean ± SEM; number of experimental animals (indicated by red dots): ; (H) n = 3 in 8 week-old mice, n = 5 in 14 month-old mice  ; dotted lines border SGZ   and GZ; scale bars = 50 µm.",
    "ncbi_link": "GFP: 
Cre: 2777477
ER: 2099
Nestin: 18008"
  },
  {
    "caption": "RNAi injections schedule in starved conditions. Planarians are at 14dS when the amputation is performed (indicated by the grey cross at day 14). Live images show that cct3A(RNAi) planarians form a minimal blastema compared to controls at the time points shown. At the bottom are the number of planarians with the phenotype shown. The remaining planarians are dead by the time point of regeneration shown. dR indicates days of regeneration. RNAi injections schedule in feeding conditions. One extra feeding in respect to (B) is introduced one day prior to injections. Planarians are at 8dS when the amputation is performed. The live images show that most of the cct3A(RNAi) planarians regenerate like controls. At the bottom are the number of planarians with the phenotype shown. At 8-10dR, the remaining planarians are either dead (4/124) or have a tiny blastema (23/124) and either died or regenerated later. At 51-68dR, the remaining planarians are either dead (10/93) or have a tiny blastema and died later (5/93).",
    "ncbi_link": "cct3A: "
  },
  {
    "caption": "The graph shows the mitotic numbers of trunks during different time points of regeneration in the starved condition for cct3A RNAi and controls. Error bars are s.d. from the mean and asterisks indicate P < 0.001 (three asterisks), P < 0.01 (two asterisks) and n.s. indicates not significant using two-tailed Student's test with equal variance. n ≥ 9 planarians per time point. Also shown are maximum projections of representative trunks labelled with anti-H3P at different time points of regeneration in the starved condition. On the bottom, the number of planarians with the phenotype shown from the total is displayed. Note that at 50dR planarians show few (a4) or no mitoses (a5). The dashed line delimits the body of the planarian.",
    "ncbi_link": "cct3A: "
  },
  {
    "caption": "Maximum projections of representative trunks after FISH for smedwi-1 at different time points of regeneration under starved and feeding conditions. On the bottom, the number of planarians with the phenotype shown from the total is displayed. At 15dR the expression levels are similar. At 30dR some planarians have almost no expression (c5) and at 50dR almost all planarians show no expression (c10 and c11) in starved conditions. Under the feeding condition the expression levels at 30dS are similar. On the bottom, the number of planarians with the phenotype shown from the total is displayed. The dashed line delimits the body of the planarian.",
    "ncbi_link": "smedwi-1: "
  },
  {
    "caption": "Volcano plot displaying DEGs in starved cct3A(RNAi) planarians compared to controls at 72hR (q-value < 0.05). Y-axis indicates the negative log10 of the false discovery rate (FDR) (q- value). X-axis indicates the beta values (b), a biased estimator of the fold change. For better visualization, 13 dots with -log10 (q-value) > 20 are not displayed. This includes cct3A with q = 0. Notice that when down-regulating cct3A in starved planarians, xbp1, atf6, bip-1 and a repertoire of ER chaperones are down-regulated, whereas dnajb9, a repressor of the UPR, and other ccts are up-regulated.",
    "ncbi_link": "bip-1: 
atf6: 
cct3A: 
dnajb9: 
xbp1: "
  },
  {
    "caption": "Live images show that xbp1/atf6(RNAi) planarians in starved conditions form a minimal blastema when compared to controls while at the feeding condition most of them can regenerate as controls. The remaining planarians in the starved condition are dead by the time point of regeneration shown. In the feeding condition, the remaining planarians at 8-10dR are either dead (13/145) or have a tiny blastema and died or regenerated later (40/145) while at 21-27dR are dead.",
    "ncbi_link": "atf6: 
xbp1: "
  },
  {
    "caption": "Maximum projections of representative regenerating trunks after FISH for smedwi-1 in starved conditions. The dashed line delimits the body of the planarian.",
    "ncbi_link": "smedwi-1: "
  },
  {
    "caption": "Quantification of the percentage of stem cells in different mitotic phases and the percentage of defective mitotic figures in 72hR anterior blastemas of xbp1/atf6 RNAi and controls in starved conditions after double immunostaining with anti-tyrosine-tubulin and anti-H3P (****P < 0.0001, ***P < 0.001, *P < 0.05, n.s. indicates not significant using two-sided Chi-square test); n ≥ 5 planarians. Representative images are shown. Arrows indicate abnormal organization or number of spindle poles. j8 displays asymmetrical distribution of chromosome content.",
    "ncbi_link": "atf6: 
xbp1: "
  },
  {
    "caption": "The Kaplan-Meier curve demonstrates increased survival of cct3A RNAi animals when treated with DTT under starved conditions. Percentages indicate the number of survivals at the indicated time points. Three asterisks indicate p < 0.001 with log-rank (Mantel-Cox) test. Images are representative surviving animals for the different conditions at the displayed time point of regeneration. At the bottom are the number of planarians with the phenotype shown. The rest of planarians are dead at the displayed time point.",
    "ncbi_link": "cct3A: "
  },
  {
    "caption": "Volcano plots displaying shRNA-Cct3- and shRNA-luciferase-infected LSK cells cultured either in normal glucose (upper graph) or low glucose conditions (lower graph). Dots represent all the NanoString analyzed transcripts. Red dots are UPR and ER stress related genes. The UPR and ER stress genes significantly down-regulated only under low glucose conditions in shCct3 cells compared to controls are indicated near the lower graph. For better visualization two dots with q ≤ 0.001 have been removed from the volcano plot (see them in Dataset EV4). Y-axis indicates the false discovery rate (FDR) (q- value), and the X-axis indicates the log2 fold changes. The FDR-based method of p-value adjustment was conducted to calculate the q-values by nSolver software using Benjamini-Hochberg methods. Significance is established by q-value < 0.05 and indicated by the dotted horizontal line. n= 3 mice.",
    "ncbi_link": "luciferase: 
Cct3: 12462"
  },
  {
    "caption": "The Kaplan-Meier curve demonstrates increased survival of starved cct3A(RNAi) animals when treated with palmitic acid/palmitoylcarnitine (PA/PC). Percentages indicate the number of survivals at the indicated time points. Three asterisks indicate P < 0.001 with log-rank (Mantel-Cox) test.",
    "ncbi_link": "cct3A: "
  },
  {
    "caption": "K. Representative data showing OTI CD8+ T cells proliferation  3 days after activation with Listeria-OVA  (left panel, orange) or Listeria  ∆hly -OVA  (right panel, blue) BacB cells. Non-activated naïve CD8+ T cells  (grey) are shown as a negative proliferation  controls.",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "M. Representative data showing OTI CD8+ T cells proliferation  3 days after activation with Listeria-OVA  (orange), Listeria  ∆hly-OVA  (blue) or Listeria  ∆hly::hly-OVA BacB cells (Purple).",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "F. Kaplan Meier survival curve of Rag1-/- mice  after adoptive transfer and bacteria challenge. Data information: Bars in the figure represent the mean. Error bars indicate the SD. Statistical significant differences, analyzed by ANOVA are represented by asterisk; *P<0.05, ***P<0.0005, non-significant differences are marked as (ns). …",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "H. BacB cells reduce melanoma  growth.  B16 F10 melanoma  cells (4 × 105) were injected s.c. in the mid-right flank of C57BL/6J (WT) host mice  (4 mice/group; treated with BacB or untreated). Once tumors were formed and visible (6 days after imlantation) mice  were treated with Listeria TRP2   BacB cells or with vehicle (PBS) (three consecutive injections in three days). Tumor growth were monitored every 1-3 days. It is shown the mean and the SD of the tumor volume  in each group at the indicated time points. Mice  with tumors ≥ 300 mm3 were sacrified. Data information: Bars in the figure represent the mean. Error bars indicate the SD. Statistical significant differences, analyzed by ANOVA are represented by asterisk; *P<0.05, ***P<0.0005, non-significant differences are marked as (ns). …",
    "ncbi_link": "TRP2: 104042"
  },
  {
    "caption": "B. RIBEYE mutations do not alter mouse survival. Data show surviving post-weaning mice (at >P21) derived from matings between mice heterozygous for the RBEKI allele (dark red) or the RBEKO allele (bright red) normalized for the total number of mice (absolute numbers per genotype/absolute number of all mice per respective breeding strategy) The expected Mendelian ratio is indicated by the dashed line. Statistical analysis using the 2-test revealed no statistical difference between wild-type and mutant mice (RBEKI allele p=0.33; RBEKO allele p=0.11).",
    "ncbi_link": "RBE: 
RIBEYE: "
  },
  {
    "caption": "C. Representative immunoblot of retina homogenates from homozygous RBEWT/WT, RBEKI/KI and RBEKO/KO mice probed with antibodies to CtBP2 (to detect the B-domain of RIBEYE and CtBP2) and to EGFP (to detect GCamP3 in the RIBEYE A-domain GCamP3 fusion protein referred to as RIB-G3).",
    "ncbi_link": "RBE: 
RIBEYE: "
  },
  {
    "caption": "D. Measurements by RT-PCR of the relative abundance of CtBP2 and RIBEYE mRNAs using an assay that simultaneously measures both mRNAs in retina and in brain from control wild-type mice (RBEWT/WT), KI-mice expressing the RIBEYE-A-domain fusion protein with GCamP3 (RBEKI/KI), and KO mice (RBEKO/KO). These measurements were performed to test the relative expression of RIBEYE and CtBP2 in retina, and to examine whether the RIBEYE A-domain KO impairs CtBP2 expression in brain, which expresses little RIBEYE. Assays are based on a qRT-PCR strategy detecting mRNAs containing the spliced connection between exon 2 and 3 which is common to both transcript isoforms (RIBEYE and CtBP2). Statistical analyses were performed using Student's t-test; data are presented as mean ± SEM (***, p<0.001; n=4 mice per genotype).",
    "ncbi_link": "RBE: 
RIBEYE: 
CtBP2: 13017"
  },
  {
    "caption": "E. Representative immunofluorescence labeling of cryostat sections from littermate wild-type and RBEKI/KI mice for EGFP (green, to detect GCamP3 in RIB-G3) and SV2 (red, to label synapses) demonstrates expression of the A-domain/GCamP3 fusion protein in knockin mice (OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, granule cell layer). Scale bar = 5 µm.",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "F. Levels of CtBP2 and of synaptic proteins in retina homogenates from littermate RBEWT/WT and RBEKO/KO mice. Levels were determined by quantitative immunoblotting using fluorescently labeled secondary antibodies; results are normalized to loading controls depending on molecular weights (actin, fodrin, VCP, and GDI) and to wild-type controls. Statistical analyses were performed using Student's t-test; data are presented as mean ± SEM (*, p<0.05; n=4 mice per genotype).",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "G. Immunofluoresence labeling for CtBP2 (green, to label RIBEYE) and mGluR6 (red, to label photoreceptorsynapses) in cryostat sections from littermate RBEWT/WT and RBEKO/KOmouseretinas demonstrates that the KO abolishes RIBEYE expression (OPL, outer plexiform layer). Scale bars: 5 µm.",
    "ncbi_link": "RBE: 
RIBEYE: "
  },
  {
    "caption": "A. Overview of the synaptic organization of the retina in RBEWT/WT and RBEKO/KOmice. Cryostat sections from littermate mice were labeled by double immunofluorescence for the RIBEYE B-domain (CtBP2; green) and SV2. Scale bar: 20 µm; abbreviations: ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer.",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "B. Double immunofluorescence staining of retinas from RBEWT/WT and RBEKO/KO mice for PSD95 (green, to label postsynaptic specializations) and mGluR6 (red, to label specifically postsynaptic sites formed by bipolar neurons in photoreceptorsynapses). Abbreviations are as in A. Scale bars: 20 µm (left and right overview), 5 µm (left panel magnification), 2 µm (right panel magnification).C. Same as B, except that retinas were stained for PKCα (green, to label bipolar neurons) and PSD95 (red, to label amacrine cells).",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "A and B. Double immunofluorescence staining of retinas from RBEWT/WT and RBEKO/KO mice, respectively, for PSD95 (green, to label presynaptic photoreceptor terminals) and Cav1.4 (red, to label presynaptic Ca2+-channel). Scale bar: 20 µm; abbreviations: ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer. (A1 to A4) Magnification of Cav1.4 staining in the outer plexiform layer (OPL) in the retina of RBEWT/WT and (B1 to B4) RBEKO/KO mice. White arrow heads indicate Ca2+-channel distribution at selected synapses. Images represent 2 µm z-stack projections. Scale bar: 2 µm.",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "A. Transmission EM demonstrates the absence of synaptic ribbons in presynaptic terminals of photoreceptorribbon synapses in RBEKO/KOmice, while synaptic ribbons are readily visible in the terminals of RBEWT/WTmice. Asterisks in A2 and A3 denote photoreceptor active zones of RBEKO/KOmice in which the synaptic ribbon is absent. Except for the absence of synaptic ribbons, the ultrastructural appearance of the presynaptic terminals is comparable to that of RBEWT/WTmice. Abbreviations: sr, synaptic ribbon; pre, presynaptic; post, postsynaptic. Scale bars: 500 nm.",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "B. Transmission EM demonstrates absence of synaptic ribbons in presynaptic terminals of bipolar cellribbon synapses in RBEKO/KOmice, while synaptic ribbons are readily visible in the terminals of RBEWT/WTmice. Except for the absence of synaptic ribbons, the ultrastructural appearance of the presynaptic terminals is comparable to RBEWT/WTmice. Abbreviations are the same as in A. Scale bars: 1 µm (B1, B2, B4, B5); 300 nm (B3, B6).",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "A and B. Representative transmission EM pictures of RBEWT/WT (A) and RBEKO/KO (B) photoreceptor ribbon synapses (blue rectangles, area adjacent to synaptic junction used for measuring junction-associated vesicle density [size = 200 nm x 300 nm]; black squares, are in the presynaptic cytosol used to measure cytosolic synaptic vesicles [size = 200 nm x 200 nm]).C. Average vesicle ratio (expressed as vesicle numbers in the area adjacent to synaptic junctions (blue rectangle) or the cytosol (black square) normalized to RBEWT/WT.D. Average number of docked vesicles within a 150 nm range in the vicinity of the active zone.",
    "ncbi_link": "RBE: "
  },
  {
    "caption": "A. Experimental design and representative traces for analysis of synaptic transmission in retinas from wild-type (black) and RIBEYE KO mice (red). Presynaptic bipolar neurons were depolarized in voltage-clamp mode from -70 mV to -10 mV for 0.5 s as indicated on top to open Ca2+-channels and trigger release. Presynaptic Ca2+-currents and postsynaptic EPSCs were measured simultaneously as indicated in the traces; dotted box displays an expansion of the initial Ca2+-currents and EPSCs.B. RIBEYE KO does not alter presynaptic Ca2+-currents. Summary graphs show average peak Ca2+-currents and Ca2+-current.C. RIBEYE KO severely impairs EPSCs triggered by presynaptic depolarization. Plot shows integrated EPSC charge as a function of time; both initial and sustained neurotransmitter release are impaired.D. RIBEYE KO strongly reduces initial synchronous release induced by presynaptic depolarization as indicated by the summary graph of the peak EPSC amplitude.E. RIBEYE KO suppresses both the initial synchronous and the sustained phase of release induced by presynaptic depolarization. Summary graphs display integrated EPSC charges for the initial phase (0-50 ms) and the sustained phase (50-500 ms).F. RIBEYE KO does not alter the kinetics of EPSCs. Summary graphs depict the mean synaptic delays (left), rise times (center) and decay time constants (right) of EPSCs.",
    "ncbi_link": "RIBEYE: "
  },
  {
    "caption": "A. Representative mEPSCs recorded from AII cells in wild-type (black) and RIBEYE KO mice (red). The insets in dashed boxes show mEPSCs on expanded scales, while the inset in a continuous box on the right shows the averaged mEPSC waveforms (average of 100-200 isolated mini events) of the example cells. Calibration bars apply to wild-type and mutant EPSCs.B. RIBEYE KO does not alter fundamental parameters of mEPSCs. Summary graphs show mean mEPSC frequency, amplitude, integrated charge, rise time, and decay time constant. Note that the only excitatory inputs into AII amacrine cells is provided by bipolar cell synapses.",
    "ncbi_link": "RIBEYE: "
  },
  {
    "caption": "C and D. RIBEYE KO renders mEPSCs sensitive to the slow Ca2+-buffer EGTA (C, representative mEPSCs traces recorded from AII cells after 30 minutes incubation in DMSO or EGTA-AM [0.2 mM]; D, summary graphs of the mean mEPSC frequency (left) and amplitude (right) after incubation in DMSO or EGTA-AM).",
    "ncbi_link": "RIBEYE: "
  },
  {
    "caption": "Representative immunofluorescence  images of SCOTIN-KO cells expressing Str-Ii-SCOTIN-SBP-EGFP  with 40 μM D-biotin treatment for the indicated times. B Upper, localization  of RUSH reporters retained on the ER membrane with Sec61β  (red). Bottom, localization  of released RUSH reporters after 240 min of biotin  treatment. The arrow indicates the EGFP  signal on the ER. The arrowhead indicates the EGFP  signal on vesicles. The empty arrowhead indicates the EGFP  signal on the plasma membrane. Scale bar: 20 μm. Scale bars in the magnified images: 5 μm.",
    "ncbi_link": "EGFP: 
SBP: 
SCOTIN: 51246"
  },
  {
    "caption": "Representative immunofluorescence  images of SCOTIN-KO cells expressing Str-Ii-VSVG-SBP-EGFP  (green) with 40 μM D-biotin treatment for the indicated times. , Upper, localization  of RUSH reporters retained on the ER membrane with Sec61β  (red). Bottom, localization  of released RUSH reporters after 240 min of biotin  treatment. The arrow indicates the EGFP  signal on the ER. The arrowhead indicates the EGFP  signal on vesicles. The empty arrowhead indicates the EGFP  signal on the plasma membrane. Scale bar: 20 μm. Scale bars in the magnified images: 5 μm.",
    "ncbi_link": "EGFP: 
SBP: 
SCOTIN: 51246
VSVG: 1489834"
  },
  {
    "caption": "(A) Immunoblot  analysis of proteinase K protection assay. HeLa  cells were transfected with SCOTIN-Myc  (Total) and digitonin-permeabilized. The supernatants  (Cytosol) and pellet  (PNSs) were separated by centrifugation. The PNSs  were incubated with PBS  or with proteinase K (+ PK) in the presence or absence of  Triton X-100 (+PK  +Triton X).",
    "ncbi_link": "Myc: 
SCOTIN: 51246"
  },
  {
    "caption": "(B) Representative high-resolution microscopy  images of Rab5  Q79L-EGFP- and SCOTIN-DsRed-expressing HeLa  cells. Magnified images show enlarged endosomes. Ⅰ: SCOTIN  on the endosomal membrane, Ⅱ: SCOTIN  on the endosomal membrane and luminal  side. Scale bar: 10 μm. Scale bars in the magnified images: 5 μm. (C) Plot analysis of SCOTIN  relative to the Rab5  Q79L signal shown. The graph indicates the fluorescence intensity of each channel on lines Ⅰ and Ⅱ from Figure 2B. The arrow indicates the boundary of the endosomal membrane.",
    "ncbi_link": "DsRed: 
EGFP: 
Rab5: 5868
SCOTIN: 51246"
  },
  {
    "caption": "(F) Left: Representative images of Rab5   Q79L-mCherry-expressing SCOTIN-FP11 knock-in cells. Right: Plot analysis of SCOTIN-FP11 relative to the Rab5    Q79L signal shown. The graph indicates the fluorescence intensity of each channel on the lines. The arrow indicates the boundary of the  endosomal membrane. Scale bars : 10 μm. Scale bars in the magnified images: 5 μm.",
    "ncbi_link": "mCherry: 
Rab5: 5868
SCOTIN: 51246"
  },
  {
    "caption": "(B) Representative images from a PLA  with VAPA   and Rab7   in WT and SCOTIN-Dsred-overexpressing HeLa  cells. Only one primary antibody (anti-Rab7  antibody alone) served as a negative control. The PLA  color legends are inverted. Asterisks indicate transfected cells. All scale bars: 20 μm. (C) The number of PLA  signals in each cell was quantified by particle analysis with ImageJ. Data information: n: number of cells analyzed. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, *<0.05 and ****P<0.0001.",
    "ncbi_link": "Dsred: 
SCOTIN: 51246"
  },
  {
    "caption": "(F) Immunoblot  analysis of WT and SCOTIN-KO HeLa  cell lysates for VAPA, Rab7, SCOTIN, and α-tubulin.",
    "ncbi_link": "SCOTIN: 51246"
  },
  {
    "caption": "(G) Representative images from a PLA  with VAPA  and Rab7  in SCOTIN-, TMPRD-, or PRD-Myc-transfected SCOTIN-KO HeLa  cells. The PLA  color legends are inverted. All scale bars: 20 μm. (H) The number of PLA  signals in each cell was quantified by particle analysis with ImageJ. Data information: n: number of cells analyzed. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, *<0.05 and ****P<0.0001.",
    "ncbi_link": "Myc: 
SCOTIN: 51246"
  },
  {
    "caption": "(B) Representative images of VAPA-Rab7 PLA  signals taken from Str-Ii-SCOTIN-SBP-EGFP  transfected SCOTIN-KO cells after untreated (-Biotin) or biotin  treatment (+ Biotin  4 h). For the PLA  signal, the color legends are inverted. Asterisks indicate transfected cells. All scale bars: 20 μm. (C) The PLA  signals in the indicated samples were quantified by particle analysis with ImageJ. Data information: n: number of cells analyzed. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, **<0.01, ***<0.001, and ****P<0.0001.",
    "ncbi_link": "EGFP: 
SBP: 
SCOTIN: 51246"
  },
  {
    "caption": "(D) Representative images of Sec61β-Emerald- or Sec61β-PRD-Emerald-transfected SCOTIN-KO cells. Cells were stained  with RTN4  (red). Arrowheads indicate the accumulated ER membrane. All scale bars: 20 μm.",
    "ncbi_link": "Emerald: 
Sec61β: 10952
SCOTIN: 51246"
  },
  {
    "caption": "(C) HEK293  cells were transfected with SCOTIN-GST  along with empty (pcDNA3.1-Myc), SCOTIN-Myc, or SCOTIN(Δ150-177)-Myc  plasmids for 48 h. SCOTIN-GST  was  pulled down from total cell lysates using glutathione-Sepharose  beads, and the interacting  proteins were analyzed by immunoblotting.",
    "ncbi_link": "Myc: 
SCOTIN: 51246"
  },
  {
    "caption": "(D) Representative images from a PLA  with VAPA  and Rab7  in SCOTIN-KO HeLa cells reconstituted with FL SCOTIN, SCOTIN(ΔPRD), or SCOTIN(Δ150-177)-DsRed. The PLA  color legends are inverted. Asterisks indicate transfected cells. All scale bars: 20 μm.",
    "ncbi_link": "DsRed: 
SCOTIN: 51246"
  },
  {
    "caption": "(G) Representative images of VAPA-VAPA PLA  signals taken from Str-Ii-SCOTIN(Δ150-177)-SBP-EGFP  transfected SCOTIN-KO cells after untreated (-Biotin) or biotin-treated (+Bition  4 h). For the PLA  signal, the color legends are inverted. Asterisks indicate transfected cells. All scale bars: 20 μm. (H) The PLA  signals in the indicated samples were quantified by particle analysis with ImageJ. Data information: n: number of cells analyzed. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, ****P<0.0001.",
    "ncbi_link": "EGFP: 
SBP: 
SCOTIN: 51246"
  },
  {
    "caption": "(A-D) TEM  images of the ER  and endosomes  of HeLa  (A), SCOTIN-KO HeLa  (B), SCOTIN-DsRed  transfected SCOTIN-KO HeLa  (C), and SCOTIN  Δ150-177-DsRed  transfected SCOTIN-KO HeLa  (D). DsRed-positive cells were processed for EM   quantification.",
    "ncbi_link": "DsRed: 
SCOTIN: 51246"
  },
  {
    "caption": "(A) Distribution of  late endosomes  (CD63) in WT or SCOTIN-KO HeLa  cells. Representative Z projections of confocal  images are shown. The color legends are inverted. Scale bars: 20 μm. (B) Spatial distribution of late endosomes  (CD63) expressed as the fractional distance of fluorescent pixels along a straight line drawn through the endolysosomal  cloud from the nuclear  center  (0) to the  plasma membrane (1.0) from the experimental data in Figure 8A. (C) Quantification of the number of CD63-positive vesicles  per cell from the experimental data in Figure 8A. Data information: n: number of cells analyzed, with # of data points analyzed per condition given in parentheses. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, ****P<0.0001.",
    "ncbi_link": "SCOTIN: 51246"
  },
  {
    "caption": "(D) Live-image analysis of WT and SCOTIN-KO HeLa  cells expressing Rab7-EGFP. Left: confocal  images taken at time  0. Right: time-lapse  images of Rab7-EGFP  in WT and SCOTIN-KO HeLa  cells, as shown by temporal color-coded representations. Each confocal  image of late endosomes was color coded according to its acquisition time point, with images taken at 12-sec intervals over 5 min. A total of 24 color-coded images were projected to form a single image that demonstrates the dynamics of Rab7-labeled  late endosomes. White = static late endosomes. Multicolored = motile late endosomes. Boxed, magnified images highlight selected perinuclear  and peripheral  regions. Scale bar: 30 μm. Scale bars in the magnified images: 3 μm. (E) Quantification of the fractional distance of Rab7-EGFP-positive  late endosomes in WT and SCOTIN-KO HeLa  cells from the experimental data in Figure 8D. Error bars indicate the SEMs. (F) Quantification of Rab7-EGFP-positive   late endosome vesicles   per cell from the experimental data in Figure 8D. Data information: n: number of cells analyzed, with # of data points analyzed per condition given in parentheses. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, ****P<0.0001.",
    "ncbi_link": "SCOTIN: 51246"
  },
  {
    "caption": "(G, H) Live-image analysis  of Rab7-EGFP  in SCOTIN-KO HeLa  cells reconstituted with SCOTIN-DsRed  (G) or SCOTIN(Δ150-177)-DsRed  (H) taken at time  0 or for 5 min (color-coded images). Lower, boxed, magnified images of selected perinuclear  and peripheral  regions. Scale bar: 20 μm. Scale bars in the magnified images: 2 μm. (I) Quantification of the fractional distance of Rab7-EGFP  in SCOTIN-KO cells reconstituted with SCOTIN-DsRed  or SCOTIN(Δ150-177)-DsRed  from the experimental data in Figure 8G and 8H. Data information: n: number of cells analyzed, with # of data points analyzed per condition given in parentheses. Data are shown as bars with dots and represent the means±SEMs. P values were determined using a two-tailed unpaired t test. Significant differences are labeled, ****P<0.0001.",
    "ncbi_link": "DsRed: 
SCOTIN: 51246"
  },
  {
    "caption": "Representative images of seed  fluorescence segregation in 420/++ in wild type (Col) and hcr2. Scatterplots to the right show red (dsRed) and green (eGFP) fluorescence values in 420/++ Col (top) and hcr2  (bottom). Scale bars: 2 mm.",
    "ncbi_link": "hcr2: 827261"
  },
  {
    "caption": "End-point RT-PCR analysis of HSBP   in Col, hsbp-3, hsbp-2  and  hsbp-1. Hash and asterisk indicate aberrant long and short splicing variants of HSBP  in  hsbp-3, respectively. Image J was used to measure relative PCR  band intensity for hsbp-3 (53%), hsbp-2 (9%) and hsbp-1 (70%). TUB2  was used as an internal control. As in E, but showing immunoblot  analysis of HSBP. hsbp-3, hsbp-2 and hsbp-1 accumulate about 58%, 17% and 77% of HSBP  levels, respectively. Coomassie-stained  membrane was used as a loading control.",
    "ncbi_link": "HSBP: 827261
hsbp: 827261
TUB2: 836390"
  },
  {
    "caption": "Representative images of ASY1  (green) and RAD51  (red) immunostaining  in Col and hsbp-3. Nuclei  spreads were stained  with DAPI  (blue). Scale bars: 10 μm. Quantification of RAD51  foci numbers per cell in Col (blue) and hsbp-3 (red). n = 20 cells of biological replicates.",
    "ncbi_link": "hsbp: 827261"
  },
  {
    "caption": "Representative images of MLH1  (red) immunostaining  in Col, hsbp-3, hsbp-2, Col/Ler, and meiMIGS-HSBP  Col/Ler. Nuclear  DNA  was stained  with DAPI. Scale bar: 5 μm. Quantification of the number of MLH1  foci per cell shown in (G). n ≥ 32 cells of biological replicates.",
    "ncbi_link": "HSBP: 827261
hsbp: 827261"
  },
  {
    "caption": "Representative images of HEI10  (red) and ASY1  (green) immunostaining  in Col and hsbp-3. Scale bar: 2 μm.",
    "ncbi_link": "hsbp: 827261"
  },
  {
    "caption": "Immunoblot  analysis of HEI10  and HEI10-Myc in Col, hsbp-3, HEI10-myc  and HEI10-myc  plants. Experiments were performed at least three times.",
    "ncbi_link": "myc: 
HEI10: 841784
hsbp: 827261"
  },
  {
    "caption": "Summary of Hsp12-GFP dynamics single mutant screen. 68 mutants were divided into three groups: increased/decreased/did not change the total GFP produced. Each group was independently hierarchically clustered. The values shown are the Z-Scores of each parameter: ton- response onset time; production rate; total open time - length of transcriptional window (toff − ton); Basal GFP - GFP levels measured before exposure to stress; Delta GFP - amount of GFP produced throughout the experiment (Max GFP - Basal GFP).",
    "ncbi_link": "GFP: 
Hsp12: 850532"
  },
  {
    "caption": "mRNA levels of HSP12 (Y axis) as a function of time (X axis) in six representative strains.",
    "ncbi_link": "HSP12: 850532"
  },
  {
    "caption": "Comparison of RNA levels to protein levels. X axis is the sum over the HSP12 mRNA counts (see D). Y axis is the maximum over the Hsp12-GFP values. The red line indicates the best linear fit.",
    "ncbi_link": "HSP12: 850532"
  },
  {
    "caption": "Illustration of the interactions of Δhog1 in the production rate parameter. Shown the production rate of the single mutant (X axis) versus the production rate of the double mutant with Δhog1 (Y axis). The gray line marks the Hog1 single mutant levels. Points close to the gray line are ones where the value of the double mutant is close to the value of Δhog1 and defined as epistasis of Δhog1 (pink dots).",
    "ncbi_link": "hog1: 850803
Hog1: 850803"
  },
  {
    "caption": "Illustration of the interactions of Δhog1 for the total open time parameter.",
    "ncbi_link": "hog1: 850803"
  },
  {
    "caption": "Epistatic interactions of Δmck1 in the production rate parameter",
    "ncbi_link": "mck1: 855409"
  },
  {
    "caption": "Epistatic interactions of Δmck1 in the total open time parameter",
    "ncbi_link": "mck1: 855409"
  },
  {
    "caption": "Upper: HSP12 mRNA in response to osmotic stress (0.4M KCl). Lower: Estimate of Msn2/4 dependent production of HSP12 mRNA over time (difference between WT and Δmsn2Δmsn4 production profiles, Figure EV4A, Methods).",
    "ncbi_link": "HSP12: 850532
Msn2: 855053
msn2: 855053
msn4: 853803"
  },
  {
    "caption": "   Δmck1 effect on the response of all stress genes. The integral over mRNA values in WT strain (X axis) vs. the integral in the Δmck1 strain (Y values). The inset shows the integral for the HSP12 gene.   ",
    "ncbi_link": "HSP12: 850532
mck1: 855409"
  },
  {
    "caption": "addition of the Δmsn5 strain.",
    "ncbi_link": "msn5: 851935"
  },
  {
    "caption": "addition of the Δmsn5 strain.",
    "ncbi_link": "msn5: 851935"
  },
  {
    "caption": "C. LITATS1 expression upon SMAD4 knockdown (as detected by RT‒qPCR) in MDA-MB-231 cells. Cells were serum starved for 16 h and TGF-β was added for 4 h. Representative results from a minimum of three independent experiments are shown. D. LITATS1 expression (as detected by RT‒qPCR) in HEK293T cells. Cells were transfected without (Co.vec) or with the constitutively active TGF-β type I receptor (caTβRI) ectopic expression construct. Representative results from a minimum of three independent experiments are shown. E",
    "ncbi_link": "SMAD4: 4089
TGF-β type I receptor: 7046
TβRI: 7046
LITATS1: 728431"
  },
  {
    "caption": "J. RNA fluorescence in situ hybridization was performed to evaluate LITATS1 expression and subcellular localization in A549 cells. Cells were treated with or without TGF-β for 2 h. Representative images are shown in the left panel, and signal quantification data are shown in the right panel. Scale bar=10 μm. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "A. LITATS1 expression in different breast cells as measured by RT‒qPCR. Results from epithelial-like and mesenchymal-like cells are labeled in blue and green, respectively. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "C. Quantification of LITATS1 expression levels by in situ hybridization in lung adenocarcinoma tissue microarrays. Representative images (bar=100 μm) and zoomed images (bar=20 μm) of in situ hybridization results in lung adenocarcinoma and matched adjacent normal tissues. The comparison of the LITATS1 staining index between the paired tissues is shown in the right panel. Tissue pairs with higher LITATS1 expression in the normal tissue (normal) than in the lung adenocarcinoma tissue (tumor) are highlighted in red, whereas tissue pairs with lower LITATS1 expression in the normal tissue than in the tumor tissue are highlighted in green.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "D. Kaplan‒Meier survival curves of relapse-free survival in 175 breast cancer patients stratified by LITATS1 expression. LITATS1 expression was measured by in situ hybridization in breast cancer tissue microarrays.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "Kaplan‒Meier survival curves of overall survival (E) in breast cancer patients stratified by LITATS1 expression. The data were generated via Kaplan‒Meier Plotter",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "Kaplan‒Meier survival curves of distant metastasis-free survival (F) and relapse-free survival (G) in breast cancer patients and overall survival (H) in non-small cell lung cancer patients stratified by LITATS1 expression. The data were generated via Kaplan‒Meier Plotter",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "Effect of LITATS1 on TGF-β-induced EMT marker expression in MCF10A-M2 upon CRISPRa-mediated LITATS1 overexpression (A) GAPDH loading control. Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "CRISPR: 
LITATS1: 728431"
  },
  {
    "caption": "Effect of LITATS1 on TGF-β-induced EMT marker expression in MCF10A-M2 upon shRNA-mediated knockdown (B). α/β-Tubulin, loading control. The results of LITATS1 overexpression Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "D, E. An IncuCyte chemotactic migration assay was performed to evaluate the effect of LITATS1 ectopic expression (D) or knockdown (E) on TGF-β-induced MDA-MB-231 cell migration. The results of LITATS1 overexpression and E. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "F, G. In vivo zebrafish extravasation experiments with MDA-MB-231 cells upon ectopic LITATS1 expression (F) or LITATS1 knockdown (G). Representative zoomed images of the tail fin area are shown in the left panels. Extravasated breast cancer cell clusters are indicated with yellow arrows. Analysis of the extravasated cell cluster numbers in the indicated groups is shown in the right panel. Whole zebrafish image, bar=309.4 μm; zoomed image, bar=154.7 μm. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "C. Expression of TGF-β target genes (as measured by RT‒qPCR) in MDA-MB-231 cells without (Co.sh) or with (sh#1 and sh#2) LITATS1 depletion. Cells were serum starved for 16 h and treated with or without TGF-β for 4 h. Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "D. Effect of LITATS1 knockdown on TGF-β-induced SMAD2 phosphorylation in MDA-MB-231 cells. Cells were serum starved for 16 h and stimulated with TGF-β for the indicated durations. The p-SMAD2 and total SMAD2 (t-SMAD2) levels were analyzed by western blotting. GAPDH, loading control. Representative results from a minimum of three independent experiments are shown. E. Effect of LITATS1 knockdown on E-cadherin, N-cadherin and SNAIL expression in A549 cells. Cells were stimulated with vehicle control (-), SB431542 (SB; 10 μM) or TGF-β (Τβ) for 24 h, and protein expression was analyzed by western blotting. α/β-Tubulin, loading control. Representative results from a minimum of three independent experiments are shown. F",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "H. In vivo zebrafish extravasation experiments with MDA-MB-231 cells upon LITATS1 knockdown and blockage of TGF-β signaling. Representative zoomed images of the tail fin area are shown in the left panels. Extravasated breast cancer cell clusters are indicated with yellow arrows. Analysis of the extravasated cell cluster numbers in the indicated groups is shown in the right panel. Whole zebrafish image, bar=618.8 μm; zoomed image, scale bar=154.7 μm. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "A, B. Effect of ectopic LITATS1 expression (A) or LITATS knockdown (B) on TβRI expression in MDA-MB-231 cells. Right panel: quantification of relative TβRI protein levels. Vinculin or GAPDH, loading control. Representative blots from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS: 728431
LITATS1: 728431"
  },
  {
    "caption": "C, D. Analysis of TβRI protein stability (as measured by western blotting) in MDA-MB-231 cells with ectopic LITATS1 expression (C) or LITATS knockdown (D). Cells were treated with CHX (50 µg/mL) for the indicated durations. Quantification of the relative TβRI protein level is shown in the lower panel. GAPDH, loading control. Representative blots from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS: 728431
LITATS1: 728431"
  },
  {
    "caption": "E. TβRI expression in MDA-MB-231 cells with ectopic LITATS1 expression in the absence or presence of lysosome or proteasome inhibitors. Cells were incubated with vehicle control DMSO (-), the lysosome inhibitor BafA1 (20 nM) or HCQ (20 μM), or the proteasome inhibitor MG132 (5 μM) for 8 h. Vinculin, loading control. Representative results from a minimum of three independent experiments are shown. F. Effect of LITATS1 on TβRI ubiquitination. HEK293T cells were transfected with ectopic expression constructs for HA-Ubiquitin (HA-Ub), caTβRI-FLAG and/or LITATS1. TβRI polyubiquitination was analyzed by western blotting. Representative blots from a minimum of three independent experiments are shown. D",
    "ncbi_link": "HA: 
LITATS1: 728431"
  },
  {
    "caption": "B. Interactions between LITATS1 and TβRI or SMURF2 in MDA-MB-231 cells were detected by the CARPID approach. Cells with stable expression of TurboID-dCasRx were transduced without (Co.) or with (#1 and #2) LITATS1 targeting gRNAs. Cells were stimulated with or without TGF-β (2.5 ng/mL) for 2 h and were then stimulated with biotin (500 μM) for 30 min. Western blotting was performed to detect SMURF2 and TβRI expression in whole-cell lysates (Input) and immunoprecipitates (IP). GAPDH and HA-dCasRx expression levels were measured for equal loading of Input samples and as the negative control or positive control, respectively, for proximity biotinylation in immunoprecipitate (IP) samples. Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "dCasRx: 
TurboID: 
LITATS1: 728431"
  },
  {
    "caption": "C. Interactions between LITATS1 and TβRI (left) or SMURF2 (right) were analyzed by RIP. MDA-MB-231 cells were stimulated with or without TGF-β (5 ng/mL) for 4 h before RIP. RT‒qPCR was performed to detect LITATS1 expression in immunoprecipitates from MDA-MB-231 cells. IgG was included as the control for immunoprecipitation. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "D. Interactions between LITATS1 and caTβRI or SMURF2 were analyzed by RNA pull-down. Biotinylated 25x poly(A), antisense LITATS1 (LITATS1-AS) or LITATS1 was incubated with lysates from HEK293T cells transfected with the caTβRI-HA or MYC-SMURF2 expression construct. Western blot analysis was performed to detect HA or MYC expression in whole-cell lysates (Input) and immunoprecipitates (IP). Representative blots from a minimum of three independent experiments are shown.",
    "ncbi_link": "HA: 
MYC: 
SMURF2: 64750
TβRI: 7046
LITATS1: 728431"
  },
  {
    "caption": "E. In vitro RNA pull-down assays were performed to evaluate the interactions between LITATS1 and SMURF1/2. In vitro-transcribed Antisense LITATS1 (LITATS1-AS) or LITATS1 (LITATS1-S) was incubated with recombinant FLAG-tagged SMURF1 or SMURF2 protein. Western blotting analysis was performed to evaluate FLAG expression in input and IP samples. The amounts of RNA probes used for RNA pull-down were evaluated by agarose gel electrophoresis. Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "G. Effect of LITATS1 overexpression on SMURF2-mediated TβRI polyubiquitination. HEK293T cells were transfected with expression constructs for HA-Ubiquitin (HA-Ub) and caTβRI-FLAG and ectopic expression constructs for SMURF2 and/or LITATS1. Polyubiquitination of TβRI was evaluated by western blotting. Representative blots from a minimum of three independent experiments are shown.",
    "ncbi_link": "FLAG: 
HA: 
SMURF2: 64750
TβRI: 7046
LITATS1: 728431"
  },
  {
    "caption": "H. Effect of SMURF2 knockdown on LITATS1-mediated TβRI polyubiquitination. MDA-MB-231 cells with stable HA-Ub expression were transduced with expression constructs for LITATS1 and/or two different SMURF2 shRNAs, as indicated. Polyubiquitination of TβRI was evaluated by western blotting. Representative blots from a minimum of three independent experiments are shown.",
    "ncbi_link": "HA: 
SMURF2: 64750
LITATS1: 728431"
  },
  {
    "caption": "A. An in vitro RNA pull-down assay was performed to evaluate the interaction between LITATS1 truncation mutants and SMURF2. Recombinant FLAG-SMURF2 protein was incubated with antisense LITATS1 (LITATS1-AS), LITATS1 (LITATS1-S), or LITATS1 truncation mutants (T1-T4). Western blot analysis was performed to evaluate FLAG expression in immunoprecipitates (IP). The amounts of RNA probes used for RNA pull-down were evaluated by agarose gel electrophoresis. Representative results from a minimum of three independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "E. SMURF2 expression and localization (as measured by immunofluorescence) upon LITATS1 depletion in A549 cells. DAPI staining was performed to visualize nuclei. Scale bar=23.2 μm. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "F. Effect of LITATS1 knockdown on SMURF2 localization in A549 cells. After subcellular protein fractionation, western blotting was performed to detect SMURF2 expression in whole-cell lysates (Total) and the cytoplasmic (Cyto) and nuclear (Nuc) fractions. The levels of the cytoplasmic marker GAPDH and the nuclear marker Lamin A/C are included to demonstrate subcellular protein fractionation. Representative results from two independent experiments are shown.",
    "ncbi_link": "LITATS1: 728431"
  },
  {
    "caption": "G Activity of PBMCs challenged with ORNs and total S. aureus (Sa) RNA (Myd88d/d, mutant MyD88 expression not impairing LPS driven IL-8 production; n = 2).",
    "ncbi_link": "Myd88: 4615
MyD88: 4615"
  },
  {
    "caption": "I Activity of parental and Unc93b1-/--3ddiTHP-1 cells challenged with ORNs (n = 3).",
    "ncbi_link": "Unc93b1: 81622"
  },
  {
    "caption": "B, C Responsiveness of Unc93b1-/--3ddiTHP1 cells treated with T2.5 and challenged with heat inactivated (hi) bacteria (triangle, decreasing doses; n=3).",
    "ncbi_link": "Unc93b1: 81622"
  },
  {
    "caption": "E, F NF-κB driven relative luciferase activity (Rel. luc. act.) of hTLR8 overexpressing HEK293 and murine RAW264.7 cells, respectively, upon challenges (vector, empty plasmid; n = 3).",
    "ncbi_link": "NF-κB: 4790
TLR8: 51311"
  },
  {
    "caption": "G Transfection of TLR8 siRNA impairs 3ddiTHP1 cell responsiveness (n = 3).",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "C Responsiveness of Tlr8-/--3ddiTHP1 cells challenged with heat inactivated (hi) bacteria (triangle, decreasing doses; *, p ≤ 0.05; **, p ≤ 0.01) upon TLR2 blockade (T2.5).",
    "ncbi_link": "Tlr8: 51311"
  },
  {
    "caption": "E-H NF-B driven relative luciferase activity (Rel. luc. act.) of hTLR8+ HEK293 cells or cytokine release by PBMCs all transfected with RNAs indicated and additional uridine (U) if indicated (n.p., not performed; vector, empty plasmid).",
    "ncbi_link": "NF-B: 4790
TLR8: 51311"
  },
  {
    "caption": "Figure 2. SPOP localizes to nuclear speckles or other nuclear bodies. Confocal microscopy images of fixed NIH 3T3 cells transiently expressing (A) full length HA-SPOP, (B) GFP-Gli31455, and (C) HA-SPOP+GFP-Gli31-455 are shown. DAPI was used to stain the nucleus, SPOP localization was identified using a anti-HA antibody, nuclear speckle localization was identified using a anti-SC-35 antibody, and Gli31-455 localization was identified via GFP fluorescence. SPOP co-localizes with a marker for nuclear speckles or with the substrate Gli31455. The areas with overlapping HA- and GFP signal contain 75% of the punctate HA signal, and 100% of the punctate GFP signal.",
    "ncbi_link": "Gli3: 14634
SPOP: 20747"
  },
  {
    "caption": "(A-B) NIH 3T3 cells were (A) co-transfected with constructs expressing full length SPOP and GFP-Gli31455 or (B) transfected with a construct expressing SC-35-GFP, and GFP fluorescence was monitored in live cells. (A) Snapshots were taken from individual timepoints as noted in the Figure to show photobleaching (at 0 s), recovery, and nuclear body fusion events. The arrow in each panel points to the body that was photobleached and subsequently fuses with another body. These data were not used to calculate the average recovery time as the fusion event precludes accurate measurement of fluorescence recovery. (B) Snapshots at indicated timepoints show a nuclear speckle fusion event. Additional images are shown in Fig EV1.",
    "ncbi_link": "Gli3: 14634
SPOP: 20747
SC-35: 20382"
  },
  {
    "caption": "(D-E) Nuclear bodies are close to spherical. (D) Aspect ratios for speckles observed in NIH 3T3 cells transfected with constructs expressing HA-SPOP (151 cells) (D), or GFP-Gli31-455 and HA-SPOP (155 cells) (E) were calculated as described previously (Brangwynne et al, 2011). Representative individual images of cells are shown as insets in each panel.",
    "ncbi_link": "Gli3: 14634
SPOP: 20747"
  },
  {
    "caption": "(A) SEC chromatograms of given loading concentrations of SPOP28-359 are shown. The concentrations were normalized to the monomer molecular weight, i.e., identical concentrations of dimeric SPOP ΔBACK (see Fig EV2) and oligomeric SPOP28-359 contain identical numbers of protomers. (B) SEC chromatograms for SPOP constructs defective in self-association in one or both oligomerization domains are shown. Proteins were injected at the same loading concentration (533 µM) and the elution volume of globular molecular weight standards is noted above the graph. (C) SEC chromatograms of SPOP28-359 (200 µM), SPOP mutBACK (718 µM), and mixtures of the two (ratios given in the Figure, SPOP at 200 µM) are shown. The elution volume of globular molecular weight standards is noted above the graph.",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(D) Constructs for expressing full-length HA-SPOP or HA-SPOP mutants capable of oligomerization through only one (or neither) of the self-association domains were transfected into NIH 3T3 cells. DAPI was used to stain the nucleus and SPOP localization was identified using an anti-HA antibody. Experiments were performed at least twice on four biological samples. Multiple cells were examined and representative cells are shown. For additional images see Appendix Fig S3. Scale bar represents 5 µm.",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(A) Substrate binding was assayed by anisotropy using a fluorescently labeled substrate peptide. All SPOP proteins bound substrate with an affinity similar to that of SPOP28-359 (4-8 µM, see Table 2). Experimental data are shown as circles; the solid lines are fits to eq. 2 (Roehrl et al, 2004).",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(B) In vitro crosslinking assays were performed for SPOP28-359 and each mutant at 30 μM protein with the amide-specific BS3 crosslinker. Crosslinking for SPOP ΔBACK and MATH domain are shown to demonstrate that crosslinking conditions do not lead to non-specific crosslinking of protein species. (C) Crosslinking reactions were performed on whole cell lysates from cells expressing wild type SPOP, SPOP mutBACK, SPOP mutBTB, or SPOP mutBTB-BACK. SPOP1, SPOP2 and SPOPn identify SPOP monomers, dimers and larger species, respectively. For loading levels see Appendix Fig S4.",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(A) SV-AUC data for 0.2 nM AF488-SPOP ΔBACK. Fluorescence scans were collected for 12 h and are plotted against distance from the axis of rotation (circles). The data were subjected to standard c(s) analysis in SEDFIT (Schuck, 2000) and the results of this fit are shown (solid lines, rainbow color scheme).",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(B) Experimental weight-average molar mass (Mw) from CG-MALS for SPOP28-359 (orange circles) was fitted to an isodesmic self-association model in which SPOP dimers are the self-associating unit (orange line). The largest SPOP oligomer taken into account was an undecamer of SPOP dimers ((SPOP2)11). The fits from three independent experiments yielded a KD2 of 2.4 ± 0.4 µM. Lines for fits of the data to self-association models that assume formation of individual oligomeric species instead of isodesmic self-association are shown for reference (gray lines).",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(C) Experimental weight-average molar mass (Mw) from CG-MALS data (circles) and fits (solid lines) are depicted for each SPOP construct assayed, showing that a progressive increase in SPOP oligomer size is observed only when both self-association domains are interaction-competent. This Figure is comprised of data shown in Figures 6D, 7B, and Appendix Fig S5A for direct comparison.",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "(A) Native MS spectrum of 30 µM SPOP28-359 confirms that SPOP self-associates through addition of dimers. The increase in mass indicates that the dimer is the stable building block within the assemblies.",
    "ncbi_link": "SPOP: 20747"
  },
  {
    "caption": "Figure 9. The self-association deficient SPOP mutant mutBTB has a substrate degradation defect in vivo. UAS transgenes were expressed under the control of an epithelial driver C765-Gal4 in Drosophila melanogaster. (A) UAS vector served as a control and yielded a normal wing. Longitudinal veins are denoted by numbers 1-5. Expression of (B) SPOP WT resulted in a modest Hh loss-of function phenotype with fusion of LV3 and LV4 (arrow). (C) mutBTB acts in a dominant-negative manner, as evidenced by a modest Hh gain-of function phenotype with expansion of the LV3-LV4 intervein space. Expression of (D) mutBACK and (E) mutBTB-BACK does not induce a wing patterning defect. ~50 animals each were analyzed from two independent crosses.",
    "ncbi_link": "UAS: 
Hh: 42737
SPOP: 41704"
  },
  {
    "caption": "(G) RT-PCR assay showing the efficiency of the atg4daSMO.",
    "ncbi_link": "atg4da: 492528"
  },
  {
    "caption": "Immunostaining with (A-C) anti-Pvalb7 and (D-F) anti-zebrinII antibody show loss of cerebellarPurkinje cells in atg4da morphants. (A,D) Control embryos at 4.5 dpf. (B,E) Morphants with mild phenotype show partial loss of cerebellarPurkinje cells. (C,F) Morphants with strong phenotype show either total loss of Purkinje cells or presence of few differentiated neurons, which are laterally located in the cerebellum. (G-I) Labeling of cerebellar granule cells with anti-Vglut1 antibody in control and morphant embryos. (H) Mildly affected morphants show reduced expression of Vglut1 in the cerebellum. (I) Vglut1 expression is strongly reduced in embryos showing severe phenotype. White arrowheads indicate the region of cerebellum. Abbreviations: hb, hindbrain.",
    "ncbi_link": "atg4da: 492528"
  },
  {
    "caption": "(D) ACE2 levels were characterized using RNAscope. A representative 3D view of a 232 x 232 μm2 field of view of the AT  layer of an uninfected control at 3 days at air-liquid interface (3C) is shown. The nuclear labelling is indicated in electric indigo and ACE2  mRNA is labelled in spring green LUT. (G) Same as in (D) with infected LoC at 3 dpi (G) shown.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A The kinetics of release of SARS-CoV-2  progeny was assessed from samples obtained from a wash of the apical  face of the chip and the vascular effluent (A) collected at each day-post infection. (A) The  number of viral genomes in each sample was quantified using a one-step  qRT-PCR assay for the SARS-CoV-2 N gene. The starting inoculum introduced to the apical side (labelled 'Inn') corresponded to 200-300 PFU. Lines join datapoints from the same  LoC, reconstituted with (green squares) and without (dark blue circles) macrophages. Viral genome numbers within the apical wash showed a declining trend over 3 days of infection. Viral genomes are not detected ('nd') in the vascular effluent for all the chips shown. Data information: In all plots, the bars represent the mean value, and the error bars represent the standard deviation, the solid black line in (A) represents the median.",
    "ncbi_link": "N gene: 43740575"
  },
  {
    "caption": "(M) Plot of the fold change in expression of TJP1  (AT and endothelial  layers) and CDH5, CD31, and CD146 (endothelial layers only) in infected LoCs at 1 and 3 dpi (n=3 biological replicates in each case) vs, uninfected controls (n=3 biological replicates). (N) Plot of the fold change in gene expression of  endothelial cell specific coagulation markers - Tissue Factor (F3), Tissue Factor Pathway Inhibitor (TFPI), Thrombomodulin (THBD), Plasminogen Activator Inhibitor (SERPINE1) and von Willebrand Factor (VWF) in infected LoCs  at 1 and 3 dpi (n=3 biological replicates in each case) vs. uninfected controls (n=3 biological replicates). Data information: In all plots, bars represent the mean value and error bars represent the standard deviation. Scale bar = 20 μm. P-values are calculated using a one-way Kruskal-Wallis ANOVA test, * represents p≤0.05, ** represents p≤0.01, ** represents p≤0.001. ",
    "ncbi_link": "CDH5: 1003
F3: 2152
Tissue Factor: 2152
CD146: 4162
CD31: 5175
Plasminogen Activator Inhibitor: 5054
SERPINE1: 5054
TFPI: 7035
Tissue Factor Pathway Inhibitor: 7035
THBD: 7056
Thrombomodulin: 7056
TJP1: 7082
von Willebrand Factor: 7450
VWF: 7450"
  },
  {
    "caption": "(A-H) 3D views of 232 x 232 μm2 fields of view of the AT  (A, G) and endothelial  layer (B, H) from infected LoCs reconstituted without macrophages at 1 (A, B) and 3 dpi (G, H). Orf1ab  antisense RNA, S RNA, ACE2  mRNA, and nuclear staining with DAPI  are false-colored pink, amber, spring green, and electric indigo, respectively. (C, D) Zooms corresponding to the region in (A) highlighted with white and yellow boxes, respectively. (C) An example of infection and intracellular replication in a cell with no detectable ACE2 expression (white arrow) as well as nuclear localization of viral RNA (white arrowhead). (D) An example of an uninfected cell with ACE2 mRNA expression (yellow arrow). (E, F) Zooms corresponding to the regions in (B) representing increased nucleic acid staining (hyperplasic) and normal levels of nucleic acid staining highlighted with white and yellow boxes, respectively. (E) Examples of infection of hyperplasic endothelial cells both with and without ACE2 expression (F) Examples of endothelial cell  infection with no ACE2 expression, nuclear localization of viral RNA in an infected endothelial cell is indicated (white arrow).",
    "ncbi_link": "ACE2: 59272
Orf1ab: 43740578
S RNA: 100861536"
  },
  {
    "caption": "(A)  Expression relative to GAPDH  of pro-inflammatory cytokines  (TNFA, IL1B, IL6), interferon genes (IFNB, IFNL1, IFNL3) and interferon stimulating genes (IP10, ISG15) in the AT and endothelial  layer of infected LoCs at 1 dpi reconstituted without macrophages (n=3 biological replicates for  IFNB, IFNL1 and  IFNL3 in the AT layer, n=4 biological replicates for all other data). (B) Fold-change in the markers in (A) relative to uninfected controls (n=3 biological replicates) (data in Appendix Fig. S12) at the same timepoint. The bar represents the mean, and the error bars the standard deviation. ( Data information: The bar represents the mean, and the error bars the standard deviation. P-values are calculated using a Kruskal-Wallis One-Way ANOVA Test, * represents p≤0.05, ** represents p≤0.01, ** represents p≤0.001.",
    "ncbi_link": "IP10: 3627
GAPDH: 2597
IFNB: 3456
IFNL1: 282618
IFNL3: 282617
IL1B: 3553
IL6: 3569
ISG15: 9636
TNFA: 7124"
  },
  {
    "caption": "(D) Expression of IL6R  and ADAM17 relative to GAPDH in the  AT  and endothelial layer of infected LoCs at 1 dpi (n=3 biological replicates for the AT layer and n=4 biological replicates for  endothelial layer). (E) Fold-change in expression  of IL6 and ADAM17 in the epithelial and endothelial layers of infected LoCs at 1 dpi relative to uninfected controls (n=3 biological replicates for both layers). ( Data information: The bar represents the mean, and the error bars the standard deviation. P-values are calculated using a Kruskal-Wallis One-Way ANOVA Test, * represents p≤0.05, ** represents p≤0.01, ** represents p≤0.001.",
    "ncbi_link": "ADAM17: 6868
GAPDH: 2597
IL6R: 3570
IL6: 3570"
  },
  {
    "caption": "(F-I) 3D views of representative 232 x 232 μm2 fields of view of the AT (F, H) and endothelial layer (G, I) from infected LoCs reconstituted with macrophages at 1 (F, G) and 3 dpi (H, I). IL6 mRNA, and nuclear staining are indicated with the chartreuse and electric indigo LUTs, respectively.",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "Immunoblot with anti-HA Abs of lysates from parental (Ctrl) and tagged lines (TgCRMPa-HA3 and TgCRMPb-HA3) together with inducible-knockdown lines (TgCRMPa-HA3_iKD and TgCRMPb-HA3_iKD) treated with ATc for 0, 24 or 48h. TgROP5 was used as loading control. Two close bands around 300kDa were detected for TgCRMPa. A ~820kDa protein, corresponding to the predicted size for TgCRMPb, was observed together with a ~130kDa band.",
    "ncbi_link": "HA3: 
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Quantification of microneme secretion in TgCRMPa- and TgCRMPb-depleted tachyzoites was measured by detecting the processed form (arrowhead) of TgMIC2 (arrow) in the media. Control, TgCRMPa_iKD and TgCRMPb_iKD parasites, ATc-treated (+) and untreated (-), were stimulated with propranolol to release microneme contents. Blots were probed with anti-MIC2 (secretion of micronemes) and anti-GRA3 (constitutive secretion of dense granules). P: Parasites pellet. Sup: Supernatant from untreated parasites. Sup+Prop: Supernatant from parasites treated with propranolol. The results are representative of two independent experiments.",
    "ncbi_link": "MIC2: 7894517
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Co-immunoprecipitation of TgCRMPa and TgCRMPb. Lysates from parasites co-expressing TgCRMPa-FLAG3 and TgCRMPb-HA3 were split and incubated with either anti-FLAG (left panels) or anti-HA beads (right panels). Eluates were subjected to SDS-PAGE and immunoblotted with anti-HA and anti-FLAG Abs. Untagged, TgCRMPa-FLAG3 and TgCRMPb-HA3 parasites were used as controls. TgCRMPs robustly associate with each other.",
    "ncbi_link": "FLAG3: 
HA3: 
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Quantification of microneme secretion in control and Tg277910-depleted tachyzoites was measured as in Fig 2H. Blots were probed with anti-MIC2 (secretion of micronemes) and anti-GRA3 (constitutive secretion of dense granules). P: Parasites pellet. Sup: Supernatant from untreated parasites. Sup+Prop: Supernatant from parasites treated with propranolol. The results are representative of two independent experiments.",
    "ncbi_link": "277910: 7900354"
  },
  {
    "caption": "Immunofluorescence images of extracellular tachyzoites of untagged, TgCRMPa-HA3 and TgCRMPb-HA3 parasites, incubated either with host cell monolayers for 2min, or with ionophore A23187, to induce natural or artificial conoid extrusion, respectively. Parasites were immunostained with anti-HA Abs; DNA was labeled by Hoechst. CRMPa and CRMPb consistently accumulate at the tip of extruded conoids (arrows). The apexes of A23187-treated parasites were magnified on the right, and increased in brightness and contrast to highlight the apical dots. DIC: differential interference contrast. Quantification of the dot pattern upon A23187 treatment shown in (A). Values are expressed as percentage of parasites showing (dot) or lacking (no dot) the apical accumulation of TgCRMPa and TgCRMPb; n= number of parasites analyzed per line.",
    "ncbi_link": "HA3: 
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Immunofluorescence images of extracellular TgCRMPb-HA3 tachyzoites in presence (-ATc) or absence (+48h ATc) of TgCRMPa-FLAG3 (iKD line). Parasites were stained with anti-HA Abs to visualize CRMPb. TgCRMPb localization at the tip of the extruded conoid (arrow) disappears upon TgCRMPa depletion, but it is still detected in the cytoplasm (lower panel). DNA is labeled by Hoechst. Single focal planes are shown. DIC: differential interference contrast.   Quantification of the dot pattern shown in (C). The values are reported as in (B).  ",
    "ncbi_link": "FLAG3: 
HA3: 
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Whole cell lysates from TIR1-expressing parental line (Ctrl), HA3-miniAID-TgCRMPa_iKD (N-term) and TgCRMPa-miniAID-HA3_iKD (C-term) lines were immunoblotted with anti-HA Abs to visualize tagged CRMPa in IAA-treated and untreated samples. CRMPa was undetectable upon 24h incubation with IAA when C-terminally, but not N-terminally, tagged with the miniAID-HA3, suggesting that the C-terminus is the one exposed towards the cytosol. TgMIC2 was used as loading control and detected with anti-MIC2 Abs. MW: molecular weight standards.",
    "ncbi_link": "HA3: 
TIR1: 
CRMPa: 7894778"
  },
  {
    "caption": "Immunofluorescence images of extracellular A23187-treated parasites expressing either N-or C-terminally HA3-tagged TgCRMPa, and immunostained as in (A). TgCRMPa accumulates at the tip of extruded conoids (arrows) in triton-permeabilized (+) or non-permeabilized (-) parasites. DIC: differential interference contrast. Single focal planes are shown.   Quantification of the dot pattern upon natural (+H F Fibroblasts) or artificial (+A23187) conoid extrusion in parasites expressing either N- or C-terminally HA3-tagged TgCRMPa. Values are reported as in (B).  ",
    "ncbi_link": "HA3: "
  },
  {
    "caption": "Ultrastructure Expansion Microscopy of extracellular tachyzoites, either untagged or co-expressing TgCRMPa-HA3/TgCRMPa-TY2 and TgCRMPb-HA3 together or in pairwise combination with TgNd6-TY2. Parasites were treated with A23187 prior to fixation and preparation for U-ExM, and stained with anti-HA, anti-TY and anti-α/β tubulin Abs to label CRMPs, Nd6/CRMPa and microtubules, respectively. Shown are maximum intensity projections of z-stack confocal images. CRMPs overlap with Nd6 at the tip of the extruded conoid (yellow selection). A magnified image of the apical tip of each parasite is shown on the right.",
    "ncbi_link": "HA3: 
TY2: 
Nd6: 7897938
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "Extent of colocalization between TgCRMPa-TY2 and TgCRMPb-HA3, and TgCRMPs-HA3 with TgNd6-TY2 in the apical dot shown in B. Pearson's correlation coefficient was measured using the Fiji-JACoP plugin. Values are expressed as mean ± SD. Three-five parasites per line were analyzed. Quantification of the dot pattern for TgCRMPa-HA3 and TgCRMPb-HA3 in TgNd9_iKD lines. CRMPs accumulation at the apical tip of extracellular parasites was measured as in Fig EV4A. TgCRMPs were still found in the apical dot in absence of TgNd9 (+ATc). Numbers are expressed as percentage of parasites showing (dot) or lacking (no dot) the tip accumulation of TgCRMPa and TgCRMPb. The number of parasites (n) analyzed for each line is reported at the top of the column.",
    "ncbi_link": "Nd6: 7897938
Nd9: 7899494
CRMPa: 7894778
CRMPb: 7897818"
  },
  {
    "caption": "(A-D) Relative growth  of (top) or western blot  analysis of YAP  in (bottom) the indicated prostate cancer  cell lines expressing control, YAP-WT, or YAP-5SA constructs through lentiviral  infection. Of note, LNCaP and C4-2 express full-length AR  while 22RV1 and R1-D567  express AR  splicing variants V7 and V567ES, respectively. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "AR: 367
YAP: 10413"
  },
  {
    "caption": "(M) Western blot  analysis of LATS1, LATS2, YAP, phosphorylated YAP  at S109 (pS109) and S127 (pS127) in C4-2 cells treated with two independent LATS1/2 siRNAs.",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "(E) Relative mRNA levels of AR  and the indicated AR  target genes (left) and western blot analysis of AR  (right) in  C4-2 cells treated with increasing concentrations of XMU-MP-1. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(G) Relative mRNA levels of the indicated AR  or YAP  target genes in  C4-2  cells treated with control (siNC) or YAP  siRNA (siYAP_1 or siYAP_2) for 24 hours and with or without 2 μM XMU-MP-1  for 12 hours. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Relative mRNA levels of the indicated AR  or YAP  target genes (J, in C4-2 (J, cells expressing control (NC), YAP-WT or YAP-5SA constructs through lentiviral  infection. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Western blot analysis of AR  and YAP  (I, in C4-2  cells stably expressing Tet-O-YAP-5SA and treated with 0.2 μg/ml doxycycline  (Dox) for the indicated periods of time. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Western blot analysis of AR  and YAP  L) in C4-2  cells stably expressing Tet-O-YAP-5SAS94A and treated with 0.2 μg/ml doxycycline  (Dox) for the indicated periods of time.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "relative mRNA levels of TEAD1  and TEAD4  and the indicated AR  target genes (B) C4-2 cells treated with two independent TEAD1/3/4 siRNA or control siRNA. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "TEAD1: 7003
TEAD4: 7004"
  },
  {
    "caption": "(D) Relative mRNA levels of the indicated AR  target genes (left) and western blot  analysis of TEAD  (right) in C4-2  cells expression the control or TEAD4  constructs and treated with vehicle or XMU-MP-1. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "TEAD4: 7004"
  },
  {
    "caption": "HEK-293T  cells transfected with the indicated AR, TEAD constructs. Cell lysates were immunoprecipitated  with the indicate antibodies. Immunoprecipitates  and cell lysates (input) were analyzed by  western blot  with the indicated antibodies.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(O-P) ChIP-qPCR  (O) and  RT-PCR analyses show that exogenous expression of wild type (TEAD4-WT) but not the DNA binding  deficient form (TEAD4m) of TEAD4  rescued AR binding  to the promoter/enhancer regions of KLK2  and KLK3  (O) as well as the expression of these genes (P) in  C4-2  cells treated with TEAD1/3/4 siRNA. Data information: Results are representatives of three independent experiments. Data are ± SD. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "KLK2: 3817
KLK3: 354
TEAD1: 7003
TEAD4: 7004"
  },
  {
    "caption": "(D) YAP-5SA but not YAP-5SAS94A inhibited AR/TEAD interaction. C4-2  cells stably expressing Tet-O-GFP, Tet-O-YAP-5SA or Tet-O-YAP-5SAS94A were treated with 0.2 μg/ml doxycycline  (Dox) for 10 hours, followed by CoIP  and western blot  analyses with the indicated antibodies.",
    "ncbi_link": "GFP: 
YAP: 10413"
  },
  {
    "caption": "(G-H) ChIP-qPCR analysis of AR  (G) and TEAD  (H) binding  to the promoter/enhancer regions of KLK2, KLK3  and CTGF  in Tet-O-YAP-5SA expressing  C4-2 cells treated with 0.2 μg/ml doxycycline  (Dox) for the indicated time. Data information: Results are representatives of three independent experiments. Data ± SD. ns: not significant, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "CTGF: 1490
KLK2: 3817
KLK3: 354
YAP: 10413"
  },
  {
    "caption": "Western blot  analysis of YAP  and TEAD  (left) and mRNA levels of the indicated genes (right) in C4-2  cells treated with siYAP/TAZ  for 18 (A), 36 (B), hours. Data information: Results are representatives of three independent experiments. Data ± SD. ns: not significant, *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(A-F) YAP  activation inhibited AR  positive  prostate cancer  growth in xenografts  bearing C4-2  or 22RV1 tumors  that stably express Tet-O-YAP-5SA. Male NOD scid gamma (NSG) mice  bearing C4-2 tumor  cells stably expressing a Tet-O-EGFP  construct were used as control. Male NOD scid gamma (NSG) mice  bearing the indicated tumors  were injected i.p. with PBS  containing Dox  (20mg/kg) or PBS  daily for the indicated time. Tumor growth  curve (A, D), photograph of tumor  samples (B, E), and quantification of  tumor weight  (C, F) at the end of treatment were shown. XMU-MP-1 inhibited AR  positive  prostate cancer  growth in xenografts  bearing C4-2  (G-I), tumors. Male NOD scid gamma (NSG) mice  bearing the indicated tumors  were treated daily with XUM-MP-1 at the indicated concentrations or with vehicle for the indicated periods of time. Tumor growth  curve (G, J, images of tumor samples (H, K, and quantification of tumor weight (I at the end of treatment were shown. Data information: Data are ± SD. **P<0.01, ***P<0.001 (Student's t-test). n=7 mice  for each group.",
    "ncbi_link": "EGFP: 
YAP: 10413"
  },
  {
    "caption": "(C) Long-range PCR assay to detect mtDNA deletions in TOP3A patient muscle (lanes 2-5). Samples from unaffected individuals (lanes 6 and 7) and a single-deletion mitochondrial disease patient (lane 8) are used as negative and positive controls, respectively. 'M' indicates marker.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "(A-B) Analysis of mtDNA structure in muscle from individuals with TOP3A-related mitochondrial disease using Southern blotting following restriction with BamHI (A) or PvuII (B). The black bar indicates the probe (nt. 16,262 - 128).",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "mtDNA phenotypes in U2OS Flp-In cells treated with TOP3A siRNA, rescued using variant-containing siRNA-resistant forms of TOP3A. (C) Western blot of TOP3A protein expression. Cells were untransfected (lane 1) or transfected with TOP3A siRNA (lanes 2-11), then induced to express WT TOP3A (lane 3) or pathological variants of TOP3A (lanes 4-11). Note that TOP3A Ser810* does not carry a C-terminal HA tag. β-actin is used as a loading control.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "mtDNA phenotypes in U2OS Flp-In cells treated with TOP3A siRNA, rescued using variant-containing siRNA-resistant forms of TOP3A. (D) mtDNA copy number for TOP3A rescue cells as in (C) determined using qPCR. Error bars represent SEM, n = 3 (Ala95Val) or n = 4 (all other samples), where each data point represents the mean of 3 technical triplicates. Significance values are shown for one-way ANOVA compared to untreated wild-type cells, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "mtDNA phenotypes in U2OS Flp-In cells treated with TOP3A siRNA, rescued using variant-containing siRNA-resistant forms of TOP3A. (E) Southern blot of mtDNA structure from cells as in (C). The probe (black bar, nt. 16,262 - 128) detects both full-length (FL) mtDNA and 7S DNA. The presence of hemicatenated mtDNAs is indicated. (F) Southern blot of uncut mtDNA to visualise different topological forms, from cells as in (C). Control DNA treated with BamHI (lane 1) or E. coli topoisomerase I (lane 2) act as markers for linear and relaxed monomeric mtDNA, respectively. Diagrams indicate the migration of different mtDNA forms.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "The rate of glucose uptake (a,e), lactate released after 4 h of incubation (b,f), glycolytic flux (c,g) and pentose-phosphate flux (d,h) were assessed in MEF and mouse cortical neurons in primary culture, as indicated, obtained from either WT or Pink1 KO (Pink1−/−) mice.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "Blood concentrations of glucose (i) and lactate (j), and the rate of 14C-lactate appearance in the blood from acutely injected [U-14C]glucose in the tail vein (k) of WT and Pink1 KO mice were analysed. Data are expressed as mean±s.e.m. *P0.05 (Student's t-test; n=3-4 independent experiments).",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "Quantitative real-time PCR (RT-qPCR analysis of the relative mRNA abundances of Glut1, Glut3, Hk2 and Gapdh in WT and Pink1 KO miceMEF (a) ß-Actin mRNA was used for normalization, and the Pink1 KO data are expressed as the change relative to WT.",
    "ncbi_link": "ß-Actin: 
Gapdh: 407972
Hk2: 15277
Pink1: 68943
Glut1: 20525
Glut3: 20527"
  },
  {
    "caption": "Western blot analysis of the protein abundances of PINK1, GLUT1, GLUT3 (not detectable in MEF), HK2, GAPDH and HIF1α in WT and Pink1-null mice MEF (b) ß-Actin was used as loading control.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "Quantitative real-time PCR (RT-qPCR analysis of the relative mRNA abundances of Glut1, Glut3, Hk2 and Gapdh in WT and Pink1 KO neurons (c). ß-Actin mRNA was used for normalization, and the Pink1 KO data are expressed as the change relative to WT.",
    "ncbi_link": "ß-Actin: 
Gapdh: 407972
Hk2: 15277
Pink1: 68943
Glut1: 20525
Glut3: 20527"
  },
  {
    "caption": "Western blot analysis of the protein abundances of PINK1, GLUT1, GLUT3 (not detectable in MEF), HK2, GAPDH and HIF1α in WT and Pink1-null neurons (d); ß-Actin was used as loading control.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(e) Western blot against PINK1, GLUT1, GLUT3 and HIF1α in WT and Pink1 KO mice skeletal muscle samples; α-Tubulin was used as loading control. Only representative western blots are shown per condition; the replicates and the semi-quantitative estimation of the band intensities are shown in the Supplementary Information. The mean±s.e.m. values of the mRNA data were calculated from the fold change of each ß-Actin-normalized transcript abundance in the Pink1 KO samples versus that in the WT. Thus, in all cases, the WT values were considered=1.00. *P0.05 versus the corresponding WT (Student's t-test; n=3-4 independent experiments).",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(a) RT-qPCR analysis of Hif1α mRNA abundance in MEF transfected with siHif1α, or siControl (100 nM), after 72 h.",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "(b) siHif1α effectively knockdowns expressed Hif1α cDNA WT, but not a Hif1α cDNA silent mutant form refractory to siHif1α (Hif1α cDNA REFR.) in mice MEF.",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "(c) RT-qPCR analysis of the relative mRNA abundances of Glut1, Glut3, Hk2 and Gapdh in WT and Pink1 KO mice MEF transfected with siControl or siHif1α. ß-Actin mRNA was used for normalization, and all data are expressed as the change relative to WT-siControl.",
    "ncbi_link": "ß-Actin: 
Gapdh: 407972
Hif1α: 15251
Hk2: 15277
Pink1: 68943
Glut1: 20525
Glut3: 20527"
  },
  {
    "caption": "(d) Western blot against HIF1α in WT and in Pink1 KO mice MEF transfected with siHif1α or siControl shows the efficacy of the siHif1α at knocking down endogenous HIF1α; ß-actin was used as loading control. As shown, siHif1α partially prevented the increase in GLUT1, HK2 and GAPDH protein abundances.",
    "ncbi_link": "Hif1α: 15251
Pink1: 68943"
  },
  {
    "caption": "The increased rate of lactate released after 4 h of incubation (e) and glycolytic flux (f) observed in the Pink1 KO MEF was prevented by siHif1α.",
    "ncbi_link": "Hif1α: 15251
Pink1: 68943"
  },
  {
    "caption": "siHif1α was also effective at preventing the endogenous increased HIF1α protein (g), as well as the increased glycolytic flux (h) observed in Pink1 KO primary neurons. Only representative western blots are shown; the replicates and the semi-quantitative estimation of the band intensities are shown in the Supplementary Information.",
    "ncbi_link": "Hif1α: 15251
Pink1: 68943"
  },
  {
    "caption": "(a) Mitochondrial respiratory chain complexes activity values normalized to citrate synthase (CS), and (b) mitochondrial inner membrane potential (Δψm) in WT and Pink1 KO mice MEF.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(c) Western blot against PDK1 and HIF1α in WT and Pink1 KO MEF transfected with siHif1α (or its siControl); ß-actin was used as loading control.",
    "ncbi_link": "HIF1α: 15251
Pink1: 68943"
  },
  {
    "caption": "d) PDH complex activity in WT and Pink1 KO MEF transfected with siHif1α or siControl.",
    "ncbi_link": "Hif1α: 15251
Pink1: 68943"
  },
  {
    "caption": "Rate of whole-cell H2O2 (e) and mitochondrial O2·− (f) detection in WT and Pink1 KO MEF",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(g) Detection of mitochondrial O2·− using the mitochondrial-specific probe MitoSox in MEF incubated in the absence (−) or in the presence (+) of the plasma membrane permeable GSH-EE, or by expressing mitochondrial-tagged forms of glutamate-cysteine ligase, (+mitoGCL; empty vector, pIRES2-EGFP, denoted as −) or catalase (+ mitoCAT; empty vector denoted as −), shows effective mitochondrial ROS removal.",
    "ncbi_link": "catalase: 12359
mitoCAT: 12359
glutamate-cysteine ligase: 14629///14630
mitoGCL: 14630///14629"
  },
  {
    "caption": "(h) Western blot against HIF1α in Pink1 KO MEF incubated with (or without) GSH-EE, or transfected with empty vector, mitoGCL or mitoCAT, showing reduction in HIF1α protein abundance by the treatments that remove mitochondrial ROS; α-TUBULIN was used as loading control. Only representative western blots are shown; the replicates and the semi-quantitative estimation of the band intensities are shown in the Supplementary Information. Data are expressed as mean±s.e.m. *P0.05 (Student's t-test; n=3-4 independent experiments).",
    "ncbi_link": "mitoCAT: 12359
mitoGCL: 14630///14629
Pink1: 68943"
  },
  {
    "caption": "(a) Proportion of BrdU incorporation into DNA and cell cycle phases, and (b) cell growth in WT and Pink1 KO MEF after 72 h in the absence (denoted as -2DG) or in the presence (+2DG) of the glucose-metabolizing inhibitor, 2-deoxyglucose (2DG, 1 mM).",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(c) Proportions of BrdU incorporation into DNA and cell cycle phases, and (d) cell growth in WT and Pink1 KO MEF 72 h after transfection with siHif1α (+siHif1α) or siControl (denoted as -siHif1α).",
    "ncbi_link": "Hif1α: 15251
Pink1: 68943"
  },
  {
    "caption": "(e) Ki67, Sox2 and DAPI immunostaining in the subventricular zone of WT and Pink1 KO mouse brain, and the corresponding quantification. *P0.05; #P0.05 versus all other conditions (analysis of variance followed by Bonferroni test; n=3-4 independent experiments). All data are expressed as mean±s.e.m. Scale bar, 100 μm.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "a) Rate of mitochondrial O2·- detection in WT and Pink1 KO mice primary neurons.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(b) Proportion of BrdU incorporation into DNA of WT and Pink1 KO neurons.",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(c) Proportion of apoptosis in WT and Pink1 KO neurons, as assessed by the proportion of annexin V-positive/7-AAD-negative cells, determined by flow cytometry. Data are expressed as mean±s.e.m. *P0.05 (Student's t-test; n=3-4 independent experiments).",
    "ncbi_link": "Pink1: 68943"
  },
  {
    "caption": "(A) Microcomputed tomography (micro-CT) images of the proximal femur  from 12-week-old male WT and Sigmar1  gKO mice. Scale bars, 1 mm. (B) Quantification of bone  volume per tissue volume (BV/TV), trabecular  number (Tb. N), trabecular  separation (Tb. Sp), trabecular  thickness (Tb. Th), cortical  region BV/TV (Ct. BV/TV) and cortical  thickness (Ct. Th, mm) (n = 5 biological replicates). Data information: All results are representative data generated from at least three independent experiments. Data are presented as mean ± SD. Unpaired two-tailed Student's t-test (B was used for statistical analysis.",
    "ncbi_link": "Sigmar1: 18391"
  },
  {
    "caption": "(E) TRAP staining  of tibias  from male WT and Sigmar1  gKO mice. Scale bars, 50 μm. (F and G) Quantification of osteoclast  number per bone  surface (N. Oc/BS) and percentage of osteoclast  surface per bone  surface (Oc. S/BS) (n = 6 biological replicates). Data information: All results are representative data generated from at least three independent experiments. Data are presented as mean ± SD. Unpaired two-tailed Student's t-test F-G, was used for statistical analysis.",
    "ncbi_link": "Sigmar1: 18391"
  },
  {
    "caption": "(A) Micro-CT images of the proximal femur from female WT or Sigmar1  gKO mice  that received sham  or ovariectomy   surgery for 6 weeks. Scale bars, 1 mm. (B) Quantification of bone  volume per tissue volume (BV/TV), trabecular  number (Tb. N), trabecular  separation (Tb. Sp) and trabecular  thickness (Tb. Th) (n = 5 biological replicates). Data information: All results are representative data generated from at least three independent experiments. Data are presented as mean ± SD. One-way ANOVA with Tukey's multiple comparisons test (B were used for statistical analysis.",
    "ncbi_link": "Sigmar1: 18391"
  },
  {
    "caption": "(F) TRAP staining  to detect osteoclastogenesis  of BMMs  from WT or Sigmar1  gKO mice. Scale bars, 200 μm. (G and H) Quantification of the size and nuclei  numbers of TRAP-positive multinuclear cells (n = 6 biological replicates for G and n = 3 biological replicates for H). Data information: All results are representative data generated from at least three independent experiments. Data are presented as mean ± SD. One-way ANOVA with unpaired two-tailed Student's t-test (G-H were used for statistical analysis.",
    "ncbi_link": "Sigmar1: 18391"
  },
  {
    "caption": "(I and J) Representative images and quantification of the relative pit  resorption    area of hydroxyapatite-coated plates. WT or Sigamr1  gKO BMMs  were seeded on hydroxyapatite-coated plates and treated with 50 ng/mL RANKL  (n = 6 biological replicates). Data information: All results are representative data generated from at least three independent experiments. Data are presented as mean ± SD. One-way ANOVA with unpaired two-tailed Student's t-test J) were used for statistical analysis.",
    "ncbi_link": "Sigamr1: 18391"
  },
  {
    "caption": "(D) Western blots showing SERCA2  expression  in HEK-293T  cells transfected with different amounts of Sigmar1  plasmids. The cells were transfected with 1 μg SERCA2  plasmid and Sigmar1  plasmid (0.125 μg, 0.25 μg, 0.5 μg, 1 μg). Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "SERCA2: 11938
Sigmar1: 10280"
  },
  {
    "caption": "(E) Upper: schematic representation of various Sigmar1  truncations. Bottom: mapping of Sigmar1  domains critical for SERCA2 binding.  HEK-293T cells were transfected with different Sigmar1  truncations, and cell lysates were immunoprecipitated  and subjected to western blotting. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sigmar1: 18391"
  },
  {
    "caption": "(F) Upper: schematic representation of various SERCA2 truncations. Bottom: mapping of SERCA2  domains crucial for Sigmar1 binding. Different truncated SERCA2  plasmids were transfected into HEK-293T  cells. After immunoprecipitation, the interaction between truncated SERCA2  and Sigmar1  was detected by  western blotting. Red asterisks indicate specific SERCA2  truncation bands. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "SERCA2: 11938"
  },
  {
    "caption": "(H) Western blots  showing Q615A mutant truncated SERCA2   expression in HEK-293T  cells transfected with different amounts of Sigmar1   plasmids. The cells were transfected with 1 μg Q615A mutant of truncated SERCA2  plasmid and Sigmar1  plasmid (0.125 μg, 0.25 μg, 0.5 μg, 1 μg). Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "SERCA2: 11938
Sigmar1: 10280"
  },
  {
    "caption": "(A and B) Western blots showing SERCA2  expression  in HEK-293T cells with or without Sigmar1  cotransfection treated with eeyarestatin I  or MG132 at the indicated concentration. All inhibitors were applied to cells 8 hours prior to protein collection. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sigmar1: 10280"
  },
  {
    "caption": "(C) Western blots showing changes in SERCA2  expression in HEK-293T  cells in the presence of different doses of flag-tagged Hrd1  plasmids. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "flag: 
Hrd1: "
  },
  {
    "caption": "(D) Western blots  showing alterations of SERCA2  expression in HEK-293T  cells pretreated with negative control siRNA (si-NC) or Sel1L siRNA in the presence or absence of Sigmar1. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sel1L: 6400
Sigmar1: 10280"
  },
  {
    "caption": "(E) Truncated myc-tagged SERCA2 ubiquitination  levels in  HEK-293T  cells transfected with empty vector or Sigmar1  were analyzed by immunoprecipitation. Cells were treated with MG132  (10 μM) 8 hours before harvest. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sigmar1: 10280"
  },
  {
    "caption": "(F) Expression of different truncated SERCA2  lysine mutants in HEK-293T  cells transfected with different amounts of Sigmar1  plasmid. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sigmar1: 10280"
  },
  {
    "caption": "(G) Expression  of WT or 2KR (K460A and K541A) mutants of full-length SERCA2  in  HEK-293T cells transfected with different amounts of Sigmar1  plasmid. Data information: All results are representative data generated from at least three independent experiments.",
    "ncbi_link": "Sigmar1: 10280"
  },
  {
    "caption": "D. Verification of expression of FLAG-tagged PTENα, PTENβ, and PTENε in PtenFLAG knock-in mice. Various tissues from PtenFLAG knock-in mice or control wild-type mice were lysed for immunoprecipitation with anti-FLAG M2 magnetic beads before being immunoblotted with the anti-PTENα antibody",
    "ncbi_link": "FLAG: 
Pten: 19211"
  },
  {
    "caption": "B. Reduction of PTENε in response to eIF2A knockdown. Hela cells were infected with lentivirus expressing eIF2A shRNA, eIF5 shRNA, or scramble shRNA separately. The knockdown of eIF2A or eIF5 was validated by western blot (left panel). Lysates of Hela cells were collected and subjected to western blot analysis with antibodies against PTEN, and GAPDH (right panel).",
    "ncbi_link": "eIF2A: 83939
eIF5: 1983"
  },
  {
    "caption": "C. Overexpression of eIF2A induces the relative expression of PTENε. FLAG-tagged eIF2A or eIF5 were overexpressed in DU145 cells before western blot analysis of PTENε expression with an antibody against PTEN. GAPDH was used as a loading control.",
    "ncbi_link": "FLAG: 
eIF2A: 83939
eIF5: 1983"
  },
  {
    "caption": "C. The transfected Hela PTEN-/- cells were stained with an anti-β-catenin antibody and DAPI before being imaged with confocal microscopy.",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "D. Images of immunofluorescence staining for PTENε and its interacting proteins (VASP and FSCN1). Hela PTEN-/- cells were co-transfected by a plasmid expressing C-terminal GFP-tagged PTENε with FLAG-tagged targets (FSCN1, VASP) separately, followed by staining with an anti-FLAG antibody and DAPI, and were imaged by confocal microscopy.",
    "ncbi_link": "FLAG: 
GFP: 
FSCN1: 6624
PTEN: 5728
PTENε: 5728
VASP: 7408"
  },
  {
    "caption": "E. The cell plasma membrane localization of PTENε is required for its interaction with downstream targets. FLAG-tagged CDC42, VASP, ACTR2, or FSCN1 plasmid was co-transfected with a plasmid expressing PTENε with or without 69-81aa deletion carrying C-terminal S-tag and HA tag in HEK293 cells. Cell lysates were incubated with S protein agarose before western blotting with antibodies against the FLAG tag and HA tag.",
    "ncbi_link": "PTENε: 5728"
  },
  {
    "caption": "A. Immunofluorescence staining of F-actin in PTENε or PTENε Y210L overexpressed Hela PTEN-/- cells and control cells. PTENε-GFP, PTENε Y210L-GFP, or mock construct was introduced into HeLa PTEN-/- cells respectively. The transfected cells were stained with Phalloidin and DAPI before being imaged with confocal microscopy. The scale bars represent 5 μm (left panel). White arrows shown in the magnified immunofluorescence images indicate the filopodia in the cell membrane. B. Quantification of the number of filopodia per cell by FiloQuant software and the data are presented as mean ± SD of three independent experiments and were analyzed with the unpaired t-test. ****, p<0.001.",
    "ncbi_link": "GFP: 
PTEN: 5728
PTENε: 5728"
  },
  {
    "caption": "G. Left panel: immunoblotting analyses were used to verify the level of overexpressed PTENε or PTENε Y210L in B16 cells. Middle panel: representative images showing the lung metastasis of PTENε or PTENε Y210L overexpressed B16 cells or control cells in the mouse pulmonary metastasis model (n=4). H & E, hematoxylin-eosin staining. The scale bars represent 600 mm (upper panel) and 500μm (lower panel) separately. Right panel: the representative bar graphs showing the quantification of tumor metastatic ability was displayed by measuring the number of tumor nodules (data are presented as mean ± SD based on three independent replicates). The overexpression of PTENε attenuated tumor metastatic ability compared with the vector control group. ****, p<0.0001 in the unpaired t-test.",
    "ncbi_link": "PTENε: 5728"
  },
  {
    "caption": "E, F: Acyl-rac of Gt1 cells subjected to siRNA against zDHHC9, zDHHC21 or both (72 hours post transfection), showing synergistic decrease of PIKfyve acylation by suppression of zDHHC9 and 21 (quantified in F). Each dot represents a separate experiment (unpaired t-test). **: p<0.01. Error bars represent s.e.m.",
    "ncbi_link": "zDHHC21: 68268
zDHHC9: 208884"
  },
  {
    "caption": "A: Upper row: prion-infected Gt1 cells (75 dpi) immunostained for LAMP1 showing prominent vacuoles. Control: NBH-inoculated cells. Middle row: Gt1 cells transfected with shRNA targeting PIKfyve or luciferase (control) for 5 days and immunostained for LAMP1. Depletion of PIKfyve resulted in LAMP1+ vacuoles (yellow). DAPI: nuclear stain. Lower row: prion-infected and NBH treated cells (75 dpi) contained LAMP2- vacuoles. n=3 individual biological replicates.",
    "ncbi_link": "luciferase: 
PIKfyve: 18711"
  },
  {
    "caption": "G: Lysosomal enzymes, but not β-actin, were elevated in brains of terminally scrapie-sick mice. Panels show independent triplicates. Statistics: ANOVA.. **: p<0.01. Error bars represent s.e.m.",
    "ncbi_link": "β-actin: 11461"
  },
  {
    "caption": "B: TFEB-controlled transcripts in brains of terminally scrapie-sick C57BL/6 mice were measured by qPCR. Prion infection led to upregulation of these genes, but not of STAT3. Control: NBH-inoculated mice. ANOVA on independent triplicates. ***: p<0.001. Error bars represent s.e.m.",
    "ncbi_link": "STAT3: 20848"
  },
  {
    "caption": "F: TFEB responsive genes were upregulated in Gt1 cells chronically infected with RML prions (75 dpi). Panels depict independent triplicates. Statistics: ANOVA. *: p0.05. Error bars represent s.e.m. G: TFEB responsive genes were upregulated in cells transfected with shPIKfyve for 5 days compared to shCtrl (shRNA against luciferase). Panels depict independent triplicates. Statistics: ANOVA. *: p0.05. Error bars represent s.e.m. ",
    "ncbi_link": "luciferase: 
PIKfyve: 18711"
  },
  {
    "caption": "C: Prion-infected Gt1 cells were lentivirally transduced with GADD34 at 75 dpi. Control: empty lentiviral vector. At 79 dpi, GADD34 overexpression had normalized eIF2α phosphorylation and restored PIKfyve levels. Right: Quantification of western blots (n=3; unpaired t-test). Each dot represents an individual experiment. **: p<0.01. Error bars represent s.e.m.",
    "ncbi_link": "GADD34: 17872"
  },
  {
    "caption": "A WT cells expressing OM45‐GFP, along with the uga2∆ strain over‐expressing the GAD1 gene and expressing OM45‐GFP were grown in YPL medium to mid‐log‐phase. To monitor mitophagy, strains were transferred to SD‐N starvation medium (with or without rapamycin).",
    "ncbi_link": "GAD1: 855291
uga2: 852291"
  },
  {
    "caption": "B WT strain along with the uga2∆ strain over‐expressing the GAD1 gene was grown in oleate medium and pexophagy was monitored as described in Fig , with or without rapamycin. Samples were taken at the indicated time points, and Pot1 degradation was analyzed by immunoblotting (45 kD).",
    "ncbi_link": "GAD1: 855291
uga2: 852291"
  },
  {
    "caption": "C To monitor autophagy, WT cells expressing GFP‐Atg8 along with the uga2∆ strain over‐expressing the GAD1 gene and expressing GFP‐Atg8 were grown in SD medium and transferred to SD‐N.",
    "ncbi_link": "GAD1: 855291
uga2: 852291"
  },
  {
    "caption": "A,B Example images of Parkin‐expressing HeLa cells analyzed using a tandem fluorochrome protein (mito‐RFP‐GFP) mitophagy assay under (A) control conditions or (B) displaying mitophagy depicted by the red mitochondrial structures localized to lysosomes. Bar, 10 μm.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "A Electron microscopy images of mitochondria from WT (n = 44) and SSADH‐deficient mice (Aldh5a1−/−) (n = 80) were calculated for area size.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "B Electron microscopy images showing typical sizes of WT and Aldh5a1−/− mice liver mitochondria. Bar, 0.5 μm.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "C Quantification of mitochondrial numbers from electron microscopy images of liver from WT (n = 31) and Aldh5a1−/− mice treated with vehicle (n = 39) or rapamycin (n = 34) (5 mg/kg body weight per day) via intraperitoneal injections for 3 successive days starting at day 7 of life.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "D Quantification of mitochondrial numbers from electron microscopy images of brain from WT (n = 23) and Aldh5a1−/− mice treated with vehicle (n = 30) or rapamycin (n = 41) (5 mg/kg body weight per day) via intraperitoneal injections for 3 successive days starting at day 7 of life.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "E Aldh5a1−/− mice were treated with vehicle or rapamycin (10 mg/kg body weight per day) via intraperitoneal injections for 10 successive days starting at day 10 of life. WT mice served as non‐disease controls (set to 1). After sacrifice, liver homogenates were used to measure SOD enzyme activity using a colorimetric SOD activity assay.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "G Immunofluorescence images showing typical nuclear staining (DAPI, blue) and SOD2 staining (red) from WT, Aldh5a1−/− mice treated with vehicle and Aldh5a1−/− mice treated with rapamycin. Bar, 10 μm.",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "A Quantification of S6 phosphorylation of liver lysates from WT (n = 5) and Aldh5a1−/− mice treated with vehicle (n = 4) or rapamycin (n = 5) after normalization (WT set to 1).",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "C Quantification of S6 phosphorylation of brain lysates from WT (n = 2) and Aldh5a1−/− mice treated with vehicle (n = 3) or rapamycin (n = 3) after normalization (WT set to 1).",
    "ncbi_link": "Aldh5a1: 214579"
  },
  {
    "caption": "B. IHLs were isolated from the liver of Tie2-GFP mice intrasplenically injected with NaCl (n=3) or with 5x103 CT26 at the specified time points (day 25 post-injection n=6, day 35 post-injection n=5). The number of GFP+ TEMs was estimated by flow cytometry as 7AAD-/CD45+/CD11b+/CD11c-/GFP+ cells per liver; data pooled from three independent experiments; mean values are shown; error bars=S.E.M.; p-values were calculated by Mann-Whitney test.",
    "ncbi_link": "Tie2: 21687"
  },
  {
    "caption": "E. Confocal immunofluorescence images of representative liver sections from Tie2-GFP mice that were injected intrasplenically with either NaCl (upper panels) or 5x103 CT26 (bottom panels, 25 days post-injection). Note that TEMs (identified as GFP+, macrophage mannose receptor [MMR]+ and F4/80+ cells) gather in the proximity of CRC metastatic foci (identified by the dashed lines); ✱=CRC metastatic area; scale bars=100μm.",
    "ncbi_link": "Tie2: 21687"
  },
  {
    "caption": "A. Contrast-enhanced magnetic resonance imaging (MRI) of the liver from representative Tie2-GFP mice (red frame) or Tie2-IFNα (blue frame) that were intrasplenically injected with 5x103 CT26. Red arrows identify CRC liver metastases of representative z-sections. Tumors were characterized as hypointense and slightly-hyperintense regions in T1 and T2 weighted sequences, respectively. Each panel refers to a single mouse analyzed at different time points; n.a.=not assessed, refers to a mouse euthanized before the specified time point; scale bars=5mm.B. Percentage of mice bearing at least one CRC liver metastasis estimated by MRI analysis. Mice were treated as described in A. Mock/Tie2-GFP n=11, Tie2-IFNα n=9; the oblique black line pattern within the red columns depicts the percentage of mice euthanized or that died before the indicated time point; p-values were calculated by Fisher's exact test.C. Tumor volume quantification measured by MRI analysis of the same mice described in B. Each symbol corresponds to the same mouse analyzed at different time points; horizontal bars=mean values; note that Mock/Tie2-GFP mice were euthanized or died before day 54; p-values were calculated by Mann-Whitney test.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "D, E. Quantitative real-time PCR analyses of the relative expression levels of the interferon inducible genes Oas1 (D) and Irf7 (E) within brain (n=4, n=2), kidney (n=4, n=3) and metastatic liver (n=4, n=7) of Tie2-GFP or Tie2-IFNα mice euthanized 25 days post-intrasplenic injection of 5x103 CT26. The basal expression of Oas1 and Irf7 estimated in brain of control mice (i.e. Tie2-GFP injected with saline), was set to 1 and utilized to calculate the fold increase values depicted. Mean values are shown; error bars=S.E.M.; p-value was calculated by Mann-Whitney test.",
    "ncbi_link": "IFNα: 
Irf7: 54123
Oas1: 23961
Tie2: 21687"
  },
  {
    "caption": "F. Eighty-four or 54 days post-NaCl or 5x103 CT26 intrasplenic injection, Sham/CTRL (n=5) or Tie2-IFNα mice (n=7) were infected with LCMV (Armstrong strain, 200 pfu intraperitoneally injected). Eight days post-infection white blood cells were isolated and analyzed for LCMV specific CD8+ T cell response. Left panel: percentage of total CD8+ T cells; middle panel: percentage of CD8+/NP118+ T cells (NP118=recombinant dimeric H-2d/Ig fusion protein complexed with the immune-dominant H-2d-restricted LCMV NP118-126 peptide); right panel: percentage of CD8+/IFNγ+ T cells after in vitro stimulation with virus-specific H-2d-restricted peptide (NP118-126); data pooled from two independent experiments; mean values are shown; error bars=S.E.M.; differences were not statistically significant (by unpaired Student's t-Test).",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "G. Kaplan-Meier survival curves of the indicated groups of mice described in A. Sham (n=3), Mock(wt)/Tie2-GFP (n=11); Tie2-IFNα (n=9); data pooled from three independent experiments; p=0.001 by log-rank/Mantel-Cox test. The inset images show representative macroscopic photographs of the metastatic progression in the liver of a control animal (red frame: Mock/Tie2-GFP, day 35 post-CT26 injection) opposed to the lack of lesions in Tie2-IFNα treated mice at later time points (blue frame: day 450 post-CT26 injection).",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "A. Quantitative real-time PCR analyses of the relative expression levels of the interferon inducible gene Irf7within the liver of Tie2-GFP or Tie2-IFNαmice that were intrasplenically injected with either NaCl (n=4 and n=4, respectively) or 5x105CT26-RFP and euthanized 5 minutes (n=9, n=5), 3 days (n=6, n=3) and 7 days (n=5, n=3) thereafter. The basal expression of Irf7 estimated in control mice (i.e. Tie2-GFP injected with saline), was set to 1 and utilized to calculate the fold increase values observed at the following time points post-injection. Data pooled from four independent experiments; mean values are shown; error bars=S.E.M.; p-values were calculated by Mann-Whitney test. The increase in Irf7 expression levels from the liver of Tie2-GFPmice was statistically significant (p=0.004 by one-way Anova test, not reported on graph).",
    "ncbi_link": "IFNα: 
Irf7: 54123
Tie2: 21687"
  },
  {
    "caption": "B. Representative RFP immunostaining from the liver of Tie2-GFP mice (left panels) or Tie2-IFNα mice (right panels) at the indicated time points after 5x105 CT26-RFP intrasplenic injection. Arrowheads highlight single or clustered RFP positive cells; scale bars=100μm.C. Immunostaining quantification of hepatic CT26-RFP arrival (5 minutes post-injection: Tie2-GFP n=6, Tie2-IFNα n=2) and expansion (day 3 post-injection: Tie2-GFP n=6, Tie2-IFNα n=3; day 7 post-injection: Tie2-GFP n=5, Tie2-IFNα n=3) in the liver of Tie2-GFP mice or Tie2-IFNα mice that were injected with 5x105 CT26-RFP as described in B. Data pooled from two independent experiments; mean values are shown; error bars=S.E.M.; p-values were calculated by Mann-Whitney test. The increased percent of RFP+ areas in the liver of Tie2-GFP mice was statistically significant (p=0.0009 by one-way Anova test, not reported on graph).",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "A. Representative contrast-enhanced MRI panels depicting the liver of Mock/Tie2-GFP (red frame) or Tie2-IFNα (blue frame) chimeric mice. Each frame shows the metastatic progression 14 and 21 days post-intrasplenic injection of 5x104 MC38 within the indicated chimeric group. BM donors and recipient mouse strains are indicated on the left of each frame; red arrows or dashed red lines identify CRC liver metastases of representative z-sections. Tumors were identified as hypointense and slightly-hyperintense regions in T1 and T2 weighted sequences respectively; scale bars=5mm.B. Tumor volume quantification (based on MRI analyses) of lesions detected in the same livers described in A. Chimeric groups and number of mice analyzed are listed; data pooled from three independent experiments; mean values are shown; error bars=S.E.M.; p-values were calculated by Mann-Whitney test.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "B. Tumor volume quantification measured by MRI analysis of Tie2-GFP (n=6) or Tie2-IFNα mice (n=9) at the indicated time points post-transplant, one additional Tie2-IFNα mouse showed a tumor volume at day 21 of more than 820 mm3 and was statistically rejected by the Grubbs' test and not further analyzed; mean values are shown; error bars=S.E.M.; p=0.051, by Mann-Whitney test.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "C. Images (top panels) and corresponding contrast-enhanced MRI (middle and bottom panels) of the liver from representative Tie2-GFP mice or Tie2-IFNα mice that were intrahepatically injected with 5x103 CT26. White dashed lines identify macroscopic lesions. Red and green dashed lines identify hepatic or extrahepatic CRC metastases respectively from representative MRI z-stacks. Tumors detected by MRI analysis appeared as hypointense and slightly-hyperintense regions in T1 and T2 weighted sequences, respectively. Scale bars=5mm.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "D. Percentage of mice with peritoneal carcinomatosis (defined by the presence of multiple intra-peritoneal lesions) determined by MRI analysis from the same mice described in B. Note that while intrahepatic number of lesions remained similar between time points, extrahepatic tumor spreading was significantly reduced in Tie2-IFNα mice. P-values were calculated by Fisher's exact test.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "E. Confocal immunofluorescence images of representative liver sections from Tie2-GFP mice at distal (upper panels) or proximal (bottom panels) areas to CRC liver metastasis, 30 days post HSPC transplant. Note that TEMs were identified as GFP+ cells and by the concomitant expression of different levels of the myeloid cell marker CD11b+ as highlighted in the inset (merge panels, white arrows); the dashed line identifies the metastasis margin; ✱=CRC metastatic area; scale bars=100μm; insets depict the corresponding areas identified by dashed squares in the merge panels, magnified 1.5-folds.",
    "ncbi_link": "Tie2: 21687"
  },
  {
    "caption": "F, G. Quantitative real-time PCR analyses of the relative expression levels of the interferon inducible genes Irf7 and Oas1 within liver of Tie2-GFP (n=4) or Tie2-IFNα (n=4) mice euthanized 30 days post-transplant. The basal expression of Irf7 estimated in liver of control mice (i.e. Tie2-GFP injected with saline), was set to 1 and utilized to calculate the fold increase values observed. Mean values are shown; error bars=S.E.M.; p-values were calculated by Mann-Whitney test.",
    "ncbi_link": "IFNα: 
Irf7: 54123
Oas1: 23961
Tie2: 21687"
  },
  {
    "caption": "H. Kaplan-Meier survival curves of the indicated groups of mice. Tie2-GFP (n=3); Tie2-IFNα (n=5); p=0.007 by log-rank/Mantel-Cox test.",
    "ncbi_link": "IFNα: 
Tie2: 21687"
  },
  {
    "caption": "A. IHL and TEM characterization in the liver of patients described in Appendix Fig S6A. Liver samples from surgical resections (n=9) were weighted and IHLs were isolated, counted and normalized over tissue weight (left panel). Flow cytometry analysis revealed that TEMs, identified as 7AAD-/CD45+/CD11b+/CD14+/Tie2+ cells, are detectable within the total IHL populations and accumulate preferentially in the proximity of the metastatic lesions (right panel). Control=hepatic hemangioma; Distal=distal to CRC liver metastasis (>1 cm from the lesion); Proximal=proximal to CRC liver metastasis (<1 cm from the lesion); p-values were calculated by Wilcoxon matched pairs Test.",
    "ncbi_link": "Tie2: 7010"
  },
  {
    "caption": "(B) Co-immunoprecipitation experiment in S2R+ cells co-expressing FlagMyc-tagged Ythdf and Myc-tagged Fmr1. Ythdf was used as a bait via its Flag tag. The lysate was treated with Benzonase as indicated to remove interactions enabled by RNA.",
    "ncbi_link": "Ythdf: 42995"
  },
  {
    "caption": "(A) Representative Western blot analysis of protein extracts of late pupae heads (85-95h) from control, Ythdf#0/ Ythdf#0 and Fmr1∆50/Fmr1∆50 flies. The membranes were probed with anti-Profilin or anti-Actin antibodies. (B) Quantification of Profilin protein levels (mean ± SD) obtained from three independent protein-extraction and Western blot analysis as in (A). Quantification was performed using Fiji. p<0.005 = **; p<0.05 = *, measured with unpaired t-test. ",
    "ncbi_link": "Fmr1: 37528
Ythdf: 42995"
  },
  {
    "caption": "(D) Quantification of futsch mRNA levels obtained from isolated 3rd instar larvae brains of the indicated genotypes via real-time PCR analysis. Bars show average ± SD of biological triplicates. Bars are labelled with the number of replicates.",
    "ncbi_link": "futsch: 5740544"
  },
  {
    "caption": "E-G) Representative Western blot analysis of the protein level (E) and quantification of the translation efficiency of S2R+ cells transfected with the wildtype or mutated futsch reporter constructs upon control or Mettl3 KD (F) or Ythdf KD (G). LacZ dsRNA was used for the control KD. The translation efficiency was calculated as the ratio of the relative GFP protein level and GFP mRNA level. mCherry served as a normalization control for both the protein and mRNA level. Bars show mean ± s.e.m of biological triplicates. P values were determined with a Student's t-test. (n.s. = not significant; p<0.05 = *; p<0.01 = **).",
    "ncbi_link": "LacZ: 
futsch: 5740544
Mettl3: 42844
Ythdf: 42995"
  },
  {
    "caption": "(b) Decreasing autophagy levels by deletion of the Atg5 gene (left) or depletion of ATG7 by siRNA (right) significantly increases the percentage of MBd+ cells (P=0.0019 and P=0.021, respectively, n=3). Immunoblots confirm loss of the Atg5-Atg12 conjugation in mutant cells and depletion of ATG7 (asterisk). GAPDH, glyceraldehyde 3-phosphate dehydrogenase.",
    "ncbi_link": "Atg5: 11793
ATG7: 10533"
  },
  {
    "caption": "(c) Rapamycin (Rapa) and LiCl co-treatment induces autophagy and decreases the percentage of MBd+ cells (left, HeLa; P=0.0056, n=3). Immunoblots showing increased LC3-II levels confirm autophagy induction. Induction of autophagy by overexpression of Flag-tagged BECN1 reduces the percentage of MBd+ cells (right, MCF-7; P=0.0008, n=4). Ctrl, control.",
    "ncbi_link": "BECN1: 8678"
  },
  {
    "caption": "(a) Single-plane confocal microscopy images showing co-localization of the MBds and the autophagic receptor NBR1 in U2OS cells and p62-deleted MEFs. MBd markers: MKLP1 or Cep55. Scale bar, 2 μm.",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "(b) The percentage of MBd+ cells is significantly increased following the depletion of NBR1 (P=0.022, n=3), but not another autophagic receptor, p62. Co-depletion of NBR1 and p62 does not further increase MBd levels over NBR1 depletion alone.",
    "ncbi_link": "NBR1: Q14596///4077"
  },
  {
    "caption": "(c) Deletion of the p62 gene does not affect the percentage of MBd+ cells. For b and c, immunoblots verify protein loss.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(a-c) Reprogramming is more efficient after MBd enrichment. Differentiated cells (dH1f) and embryonic fibroblasts (IMR90) are reprogrammed after stable expression of either NBR1 shRNA or shNT. Emerging iPSC colonies are scored on the basis of TRA-1-60 expression. Cells depleted of NBR1 to increase MBd levels show an increase in iPSC colony formation (a,b, dH1f, 3.1±0.5-fold, n=15, P=0.00035; IMR90, 3.4±0.8-fold, n=3, P=0.02; data are mean±s.e.m.) but insignificant changes in autophagic activity (c) over shNT control. (b) Representative plates with TRA-1-60-immunostained iPSC colonies. The immunoblot (c, top) and densitometry (c, bottom; percentage of autophagic flux) show representative results (n=3); α-tubulin, loading control.",
    "ncbi_link": "NBR1: 4077"
  },
  {
    "caption": "(e,f) MBd enrichment in cancer cells leads to increased anchorage-independent growth. MKLP1-GFP-expressing HeLa cells are separated into 'MBd-high' and 'MBd-low' subpopulations. An increase in the 'MBd high' over 'MBd low' ratio is associated with an increase in soft-agar colony formation (e). No significant difference was observed when the enrichment of the MBd-high subpopulation was less than threefold. More soft-agar colonies are formed when MBds are enriched by NBR1 depletion (NBR1 shRNA) in HeLa (f, left; P=0.0012, n=3) and mouse 134-4 cells (f, right; P=0.0086, n=3); control, shNT. Data are mean±s.d., and the colony number (e,f) is the sum of INT-violet-stained colonies from ten random fields.",
    "ncbi_link": "NBR1: 17966
NBR1: 4077"
  },
  {
    "caption": "Quantitative RT-PCR analysis for IFN-β mRNA (B) levels in wild type BMMs 5 and 24 hr post-treatment with EVs respectively (1 μg/ml equals approximately 3 x 108 vesicles/ml). Data shown are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "IFN-β: 15977"
  },
  {
    "caption": "(D) IFN-β mRNA level was quantified in wild type BMMs treated with EVs at a concentration of 10μg/ml for the times indicated. Data shown are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "IFN-β: 15977"
  },
  {
    "caption": "Quantitative RT-PCR analysis for IFN-β mRNA (E) levels in either WT, MAVS- and/or RIG-I-knockdown BMMs treated for 4 hr (E) with 10µg/ml EVs from uninfected or M.tb-infected macrophages. (Control) negative control siRNA. Data shown are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "RIG-I: 230073
IFN-β: 15977
MAVS: 228607"
  },
  {
    "caption": "IFN-β protein (F) levels in either WT, MAVS- and/or RIG-I-knockdown BMMs treated for 24 hr (F) with 10µg/ml EVs from uninfected or M.tb-infected macrophages. (Control) negative control siRNA. Data shown are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "RIG-I: 230073
MAVS: 228607"
  },
  {
    "caption": "(G) Similar to above except using WT and Mavs -/- BMMs. Data shown are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(H) Similar to above except using WT and Mavs -/- BMMs. Scale bar, 20 μM. Data shown in (H) are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(J) Top chamber: WT BMMs; Bottom chamber: WT or Mavs -/- BMMs. Data shown in (J) are the mean ± SD (n = 3 wells per group) and all data shown are representative of three independent experiments (biological replicates). * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(K) Western blot analysis for phospho-TBK1 (Ser172) in WT and MAVS-knockdown BMMs treated for 4 hr with EVs from uninfected or M.tb-infected macrophages. β-actin served as a loading control. Densitometry of the western blots for (K) are shown.",
    "ncbi_link": "MAVS: 228607"
  },
  {
    "caption": "(N) IRF3 nuclear translocation was analyzed in RIG-I- or MAVS-knockdown BMMs. Scale bar, 20 μM.",
    "ncbi_link": "RIG-I: 230073
MAVS: 228607"
  },
  {
    "caption": "(B) EVs from cells infected with WT, ∆esxA or esxA-complemented (∆esxA-C) M.tb Erdman strains.",
    "ncbi_link": "esxA: 886209"
  },
  {
    "caption": "(D) EVs from cells infected with WT, ∆esxA or esxA-complemented (∆esxA-C) M.tb Erdman strains. Data shown are the mean ± SD (n = 3 per group) and all data shown are representative of three independent experiments.",
    "ncbi_link": "esxA: 886209"
  },
  {
    "caption": "qRT-PCR analysis for IFN-β mRNA (G) in WT BMMs treated with EVs for 4 hr and 24 hr respectively. The EVs were isolated from BMMs that were infected with the different M.tb CDC 1551 strains. Data shown are the mean ± SD (n = 3 per group) and all data shown are representative of three independent experiments. * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "IFN-β: 15977"
  },
  {
    "caption": "qRT-PCR analysis for IFN-β mRNA (J) in WT BMMs treated with EVs for 4 and 24 hr respectively. The EVs were isolated from BMMs that were infected with the different M.tb Erdman strains. Data shown are the mean ± SD (n = 3 per group) and all data shown are representative of three independent experiments.",
    "ncbi_link": "IFN-β: 15977"
  },
  {
    "caption": "Immunofluorescence microscopy analysis for colocalization of M.tb (GFP) with lysosome marker Lamp-1 in Mavs-/- (E and F) mouse BMMs. Cells were pre-treated for 5 hr with EVs from uninfected or M.tb-infected macrophages plus IFN-γ, and then infected with GFP-expressing M.tb for 24 hr prior to immunostaining. quantitative analysis of M.tb colocalization with Lamp-1 in Mavs-/- mouse BMMs Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Immunofluorescence microscopy as described above except using RIG-I siRNA-treated (I and J) BMMs. quantitative analysis of M.tb colocalization with Lamp-1 in RIG-I siRNA-treated mouse BMMs Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "RIG-I: 230073"
  },
  {
    "caption": "M.tb CFU in infected Mavs-/- (K) mouse BMMs pre-treated with IFN-ɣ plus EVs from uninfected (EVs_Control) or M.tb-infected (EVs_M.tb) BMMs. CFU was determined immediately after the 1 hr infection or 24 and 72 hr post-infection. Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. ; * p < 0.05, ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "M.tb CFU in control siRNA-treated (L) or RIG-I siRNA-treated (M) mouse BMMs pre-treated with IFN-ɣ plus EVs from uninfected (EVs_Control) or M.tb-infected (EVs_M.tb) BMMs. CFU was determined immediately after the 1 hr infection or 24 and 72 hr post-infection. Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. * p < 0.05, ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "RIG-I: 230073"
  },
  {
    "caption": "(A) Immunofluorescence microscopy analysis for colocalization of M.tb with Lamp-1 in WT BMMs pre-treated with EVs from macrophages infected with WT, ∆secA2 or secA2-complemented (∆secA2-C) M.tb CDC 1551 strains. The cells were pre-treated with EVs supplemented with recombinant mouse IFN-γ for 5 hr and subsequently infected for 24 hr with GFP-expressing M.tb. (B) quantitative analysis for the colocalization of M.tb with Lamp-1. Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM ; * p < 0.05 and ** p < 0.01 by two-tailed Student's t-test.",
    "ncbi_link": "secA2: 885594"
  },
  {
    "caption": "(C) M.tb CFU in WT BMMs pre-pretreated with recombinant mouse IFN-γ and EVs from macrophages infected with WT, ∆secA2 or secA2-complemented (∆secA2-C) M.tb CDC 1551 strains. Data shown are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. n.s., not significant; * p < 0.05 and ** p < 0.01 by two-tailed Student's t-test.",
    "ncbi_link": "secA2: 885594"
  },
  {
    "caption": "Immunofluorescence microscopy and quantitative analysis for colocalization of M.tb with autophagosome marker LC3 (C and D) in RIG-I siRNA-treated BMMs. Quantitative data are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM. n.s., not significant; * p < 0.05 , ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "RIG-I: 230073"
  },
  {
    "caption": "Immunofluorescence microscopy and quantitative analysis for colocalization of M.tb with markers LC3 in Mavs -/- BMMs. Quantitative data are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM. n.s., not significant; * p < 0.05 , ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Immunofluorescence microscopy quantitative analysis for colocalization of M.tb similar to ( I -L), but using Mavs -/- BMMs. NOX2 (M and N) Quantitative data are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM. n.s., not significant; * p < 0.05 , ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Immunofluorescence microscopy quantitative analysis for colocalization of M.tb similar to ( I -L), but using Mavs -/- BMMs. p47phox (O and P) Quantitative data are the mean ± SD of three independent infections and all data shown are representative of at least three independent experiments. Scale bar, 5 μM. n.s., not significant; * p < 0.05 , ** p < 0.01 and *** p < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(A and B) Quantitative analysis of immunofluorescence microscopy images for colocalization of M.tb with Lamp-1 in WT (A) and Mavs -/- (B) BMMs infected with M.tb for 24 hr and then treated for an additional 24 hr with moxifloxacin (MFX) and/or EVs from M.tb-infected BMMs (EVs+MFX) in the presence of recombinant mouse IFN-ɣ. Mock, no EVs or moxifloxacin treatment; EVs_Control, EVs from uninfected BMMs. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Mavs -/- BMMs were used and colocalization of M.tb with LC3 (F) were quantified. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Mavs -/- BMMs were used and colocalization of M.tb with NOX2 (G) were quantified. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Mavs -/- BMMs were used and colocalization of M.tb with p47phox (H) were quantified. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(I and J) M.tb CFU analysis in WT (I) and Mavs -/- (J) BMMs infected with M.tb for 24 hr followed by treatment with EVs, moxifloxacin or combination in the presence of IFN-ɣ for 24 and 72 hr. Data shown are representative of three independent infections. The results are the mean ± SD of three independent experiments. n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "Representative histopathological analysis for lung sections of Mavs -/- (D) mice that were infected with M.tb and subsequent left untreated (Mock) or treated with EVs from uninfected BMMs (EVs_Control), EVs from M.tb-infected BMMs (EVs), moxifloxacin (MXF), or combination of EVs and MXF (EVs+MXF). Data shown is representative of two independent experiments. The results are the mean ± SD (n = 4 mice per group). Scale bar, 100 μM",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "M.tb CFU in the lung and spleen of Mavs -/- (E) mice treated with EVs, MXF or combination of both. Data shown is representative of two independent experiments. The results are the mean ± SD (n = 4 mice per group). n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "ELISA analysis for, IFN-β, TNF-α, IL-1β and IFN-γ protein level in serum isolate from M.tb-infected WT (F) or Mavs -/- (G) mice treated with EVs, MXF or a combination of both. Data shown is representative of two independent experiments. The results are the mean ± SD (n = 4 mice per group). n.s., not significant; * p < 0.05, ** p < 0.01 and *** p < 0.001 by Student's t-test (two tailed).",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "A Proteins captured by BGL3 and RMRP antisense purifications. Proteins with an absolute log2 (fold change) > 1 and -log10 (p-value) > 1.3 (compared with control purification) were considered as proteins enriched by BGL3 specifically.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "C&D RNA pull-down assay for BGL3-BARD1/PARP1 interactions before and after irradiation. Biotinylated in vitro-transcribed LncRNA-BGL3 sense or antisense transcripts were incubated with HEK-293T cell lysates with or without ionizing radiation (10 Gy) with 1 hr recovery for in vitro streptavidin RNA pull-down assays, followed by Western blots using the indicated antibodies.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "HA-tagged full-length or deletion mutants of BARD1 were transfected into 293T cells. 48 hr later, BGL3 RNA pull-down assay were performed, and arrowheads indicate the bands for HA-tagged full-length or deletion mutants of BARD1",
    "ncbi_link": "HA: 
BARD1: 580
BGL3: 103344929"
  },
  {
    "caption": "HA-tagged full-length or deletion mutants of PARP1(H) were transfected into 293T cells. 48 hr later, BGL3 RNA pull-down assay were performed,",
    "ncbi_link": "HA: 
BGL3: 103344929
PARP1: 142"
  },
  {
    "caption": "A BGL3 is recruited to DNA damage sites. U2OS cells were subjected to laser micro-irradiation to generate DSBs in a line pattern. The relocation kinetics of BGL3 to DSBs was monitored by RNA fluorescence in situ hybridization (FISH) in a time course as indicated. BGL3 intensities at the laser line were normalized into a numerical value using Nikon NIS-Elements AR software (version 4.40.00). Data are presented as mean ±SD of four biological replicates.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "B Chromosome aberrations induced by BGL3 depletion. Wild-type or BGL3 depleted BJ-5ta cells were used in the metaphase spread analysis for spontaneous DNA breaks. Representative image (left panel) and the percentage of cells containing at least one DNA break (right panel). Data are presented as mean ± SD of three biological replicates. Two-tailed Student's t test, ** P<0.01.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "C MCF-7 cells were treated as indicated, and cell response to ionizing radiation were analyzed by colony formation assays (left panel). Data are presented as mean ± SEM of four independent experiments, analyzed by two-way analysis of variance (ANOVA), **P < 0.01. Knock-down efficiency of BGL3 siRNA was examined by qRT-PCR and normalized to β-Actin (middle panel), data are presented as mean ± SD of three biological replicates. Two-tailed Student's t test, **P < 0.01. Knock-down efficiency of CtIP siRNA was examined by blotting (right panel).",
    "ncbi_link": "BGL3: 103344929
CtIP: 5932"
  },
  {
    "caption": "E BGL3 deficiency inhibits DNA damage repair. Quantification of γ-H2AX foci at indicated times after irradiation (2Gy) are presented. Data shown are results of three independent experiments (100 cells for each experiment), presented as mean ± SD, two-tailed Student's t test, *P < 0.05, **P < 0.01, NS: no significant difference.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "C-F Wild-type (CTRL) or BGL3 knockdown U2OS cells were subjected to micro-irradiation; 1 hr later, cells were fixed and processed for immunostaining with indicated antibodies. Representative images of BRCA1 (C), BARD1 (D), RAD51 (E), and RPA70 (F) accumulation at sites of laser-induced DNA damage are shown.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "Parental or BGL3-deficient U2OS cells were subjected to laser micro-irradiation to generate DSBs in a line pattern. DDR factor recruitment were examined 2 hr later. Data shown are the average of three independent experiments, and 100 cells were counted for each experiment. Data are presented as mean ± SD, analyzed by two-tailed Student's t test, **P < 0.01.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "Parental or BGL3-deficient U2OS cells were subjected to laser micro-irradiation to generate DSBs in a line pattern. DDR factor recruitment were examined 2 hr later. Data shown are the average of three independent experiments, and 100 cells were counted for each experiment. Data are presented as mean ± SD, analyzed by two-tailed Student's t test, **P < 0.01.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "E U2OS cells were transfected with the indicated siRNA, and RAD51 accumulation at sites of laser-induced DNA damage were examined. Data shown are the average of three independent experiments, and 100 cells were counted for each experiment. Data are presented as mean ± SD, analyzed by two-tailed Student's t test, NS: no significant difference. Knock-down efficiency of BARD1 siRNA was examined by blotting (bottom left panel), and knock-down efficiency of BGL3 siRNA was examined by qRT-PCR and normalized to β-actin (bottom right panel), data are presented as mean ± SD of three biological replicates. Two-tailed Student's t test, **P < 0.01.",
    "ncbi_link": "β-actin: 
BARD1: 580
BGL3: 103344929"
  },
  {
    "caption": "A BGL3 promotes BARD1-HP1γ interactions. 293T cells expressing the indicated siRNAs were irradiated (10 Gy), and BARD1-HP1γ interactions examined at the indicated time points.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "B BGL3 promotes RAP80 binding to K63 ubiquitin chain in cells. 293T cells expressing the indicated siRNAs and plasmids were irradiated (10 Gy). Cell lysates were immunoprecipitated with HA beads and subjected to immunoblot with the indicated antibodies.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "C BGL3 promotes BARD1-HP1γ (up panel) and BARD1-RAD51 (middle panel) interactions in vitro. GST-HP1γ, GST-RAD51, and FLAG-BARD1 were overexpressed and purified from cells as indicated in Methods. FLAG-BARD1 was divided into two equal parts, one part was used for BARD1-HP1γ interaction analysis (up panel), and another part was used for BARD1-RAD51 interaction analysis (middle panel). BARD1-HP1γ (up panel) and BARD1-RAD51 (middle panel) interactions with or without BGL3 were respectively detected by GST pull-down assays, here GST was used as a pull-down control.",
    "ncbi_link": "FLAG: 
GST: 
BGL3: 103344929"
  },
  {
    "caption": "A PARP1 inhibitor treatment abolished BGL3 recruitment to DSBs. U2OS cells were treated with DMSO, PARP inhibitor (olaparib), ATM inhibitor (KU-55933), ATR inhibitor (VE-821) or caffeine. BGL3 recruitment to DNA damage sites was assessed by RNA-FISH assays. B Quantification of the positive cells. For each group, 100 randomly selected cells were counted. Data are presented as mean ±SD of three biological replicates. Two-tailed Student's t test, **P < 0.01, N: no significant difference. ",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "C PARP inhibitor mainly affected BGL3 recruitment at an early time point. U2OS cells were treated with DMSO or olaparib, and BGL3 recruitment was examined following laser micro-irradiation at indicated time point. Data presented are the average of three independent experiments, and 100 cells were counted for each experiment. Two-tailed Student's t test, **P < 0.01, N: no significant difference.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "D U2OS cells were transfected with the indicated siRNAs, and BGL3 recruitment to DSBs were monitored at the indicated time point by RNA FISH. Data presented are the average of three independent experiments, and 100 cells were counted for each experiment. Two-tailed Student's t test, **P < 0.01, N: no significant difference.",
    "ncbi_link": "BGL3: 103344929"
  },
  {
    "caption": "(A) Western Blot detection of ATM pS1981, SMCHD1, TRF2 and hnRNPA1 loading control in wild-type and two SMCHD1 knockout (KO1 and KO2) HeLa cells transfected with shTRF2 plasmid or EV control.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(B) Representative metaphase spreads from wild-type and SMCHD1 knockout HeLa cells transfected with shTRF2 plasmid or EV control. Telomeric signals were detected with Cy3-OO-(CCCTAA)3 and are false colored in red, DNA is stained with DAPI and is false colored in cyan. Scale bar: 5µm.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(D) Representative cell cycle profiles from two biological replicates of WT and SMCHD1 KO HeLa cells transfected with shTRF2 plasmid or EV control. Cells were stained with propidium iodide and analyzed by Flow cytometry.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(A) Western Blot detection of SMCHD1, TRF2 and hnRNPA1 in SMCHD1 wild-type or SMCHD1 knockout HeLa inducible shTRF2 cells treated with or without doxycycline for the indicated number of days (d7, d8, d11).",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(B) Quantification of telomere fusions in SMCHD1 wild-type or SMCHD1 knockout HeLa inducible shTRF2 cells treated with or without doxycycline for the indicated number of days (d7, d8, d11). Bars represent average number of fused chromosome ends. SDs were obtained from 3 independent experiments (>1,900 telomeres counted/condition/experiment). (***) P < 0.001, (**) P< 0.01; (*) P< 0.05; unpaired two-tailed Student's t-test.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(C) Terminal Restriction Fragment (TRF) analysis of telomeric DNA to detect 3'overhang processing of genomic DNA isolated from SMCHD1 wild-type or SMCHD1 knockout HeLa inducible shTRF2 cells treated as in the experiment in (B). (Left) Radiolabeled (CCCTAA)n probe was hybridized with a short run (upper panel) and long run (lower panel) native DNA gel to detect the signal of the telomeric 3' overhang. Samples used for the short and the long run were from the same digestion split into two. Exo I treatment (+ Exo) was used as a control that single stranded telomeric signal was terminal. (Right) The total TTAGGG signal in the same lane was deteced upon denaturation and hybridization with the same probe.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(D) Quantification of the telomeric overhang signal at d11 after doxycyclin addition to SMCHD1 wild-type and SMCHD1 knockout HeLa shTRF2 inducible cells. The bar graph represents the average overhang signal intensity from two biological replicates as percentage of the signal in the cells untreated with doxycycline with error bars representing the standard deviation (SD) of the sample.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "A Western blot detection of ATM pS1981, SMCHD, TRF2, γH2AX, and hnRNPA1 in WT or SMCHD1 KO Hela cells transfected with shTRF2 and EV control.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(A-C) Representative images for detection of ATM pS9181, γH2AX, and 53BP1 at telomeres in wild-type (WT) and SMCHD1 knockout HeLa cells transfected with shTRF2 plasmid and empty vector (EV) control. Immunofluoresence (IF) for ATM pS1981 (gray), γH2AX (green) and 53BP1 (yellow) was combined with telomeric (CCCTAA)3-FISH (red) and DAPI staining total DNA. Scale bars: 5µm",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014"
  },
  {
    "caption": "(A) Western blot detection of SMCHD1, ATMpS1981, CHK2 pT68, CHK1 pS345, RPA pS33, RPA pS4/8, γH2AX and Vinculin in wild-type or SMCHD1 KO HeLa cells γ-irradiated with 3Gy dose and harvested at the indicated times (1h, 12h, 24h) after the treatment.",
    "ncbi_link": "SMCHD1: 23347"
  },
  {
    "caption": "(C) Quantification of the average number of ATMpS1981 foci per cell detected as in (B) in wild-type and SMCHD1 KO γ-irradiated HeLa cells. Data represent mean of 3 independent experiments ± SD (>200 cells/condition/experiment) with individual average values indicated.",
    "ncbi_link": "SMCHD1: 23347"
  },
  {
    "caption": "(A) Western Blot detection of SMCHD1, TRF2, TPP1 and hnRNPA1 in wild-type or SMCHD1 knockout HeLa cells transfected with the indicated shRNAs (shTRF2, shTPP1, shTRF2/shTPP1) or EV control.",
    "ncbi_link": "SMCHD1: 23347
TRF2: 7014
TPP1: 1200"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). Volcano plots showing the log fold-change (X-axis) and uncorrected negative log10P value (Y-axis) of ACE2 expression changes are given for (A) 48 antihypertensive drugs The enrichment of positive/negative ACE2 expression regulators in different drug classes based on their mechanism of action (MOA) was tested with the GSEA method as implemented in the R package fgsea (Segushichev, 2016; Methods), and the enrichment significance (negative log10 P values) is shown in bar plots in (B) , for the analysis on the 48 antihypertensive drugs CCBs, calcium channel blockers; ARBs, angiotensin II type-I receptor blockers; ACEIs, angiotensin-converting enzyme inhibitors",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). (C) 672 clinically approved drugs that are each tested on four carcinoma cell lines from CMAP (Subramanian et al, 2017).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). The ACE2 expression levels in control and drug-treated groups for the top significant drugs (vorinostat, panobinostat, and isotretinoin) among the 672 clinically approved drugs are shown with boxplots in (D), the ACE2 expression log fold-change values and adjusted P values from limma, as well as the number of samples per group are labeled for each drug. In the boxplot of panel (D), the center line, box edges and whiskers denotes the median, interquartile range and the rest of the distribution in respective order, except for points that were determined to be outliers using a method that is a function of the interquartile range, as in standard box plots.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Differential expression analysis for ACE2 expression changes in treated vs control samples was performed with the level 3 CMAP data of 24 hours response values using limma (Ritchie et al, 2015; Methods). The enrichment of positive/negative ACE2 expression regulators in different drug classes based on their mechanism of action (MOA) was tested with the GSEA method as implemented in the R package fgsea (Segushichev, 2016; Methods), and the enrichment significance (negative log10 P values) is shown in bar plots in (E), for the analysis on the 672 clinically approved drugs We further extended the analysis to a larger set of 989 clinically approved drugs tested on a total of 28 cell lines (16 cancer and 12 normal cells; this list is provided in Table EV2A with details including primary site, subtype and donor demographics) where each drug may have been tested on a different subset of cells (Methods). and performed enrichment analysis using the WHO ATC drug classification data (World Health Organization, 2006), and top enriched drug classes are shown in (F).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A-D) This Fig summarizes the differential expression analysis results for ACE2 upon treatment by clinically approved drugs in samples of lung and kidney datasets mined from the GEO database, spanning both cancer and non-cancer datasets (Methods). Volcano plots showing the log fold-change (X-axis) and uncorrected negative log10P value (Y-axis) of ACE2 expression changes are displayed in (A) for 74 datasets of cells or tissue samples from lung, involving 42 clinically approved drugs, and in (C) for 35 kidney datasets involving 29 clinically approved drugs. Among these, we focused on the top significant drugs that modulate ACE2 expression in non-cancerous cells or tissue samples from lung and kidney, which are shown in (B) and (D), respectively, where the ACE2 expression (Y-axis) difference between control and treated groups (X-axis) are shown with boxplots. In the title of each boxplot, the GEO identifier of the respective studies and the corresponding drug name and the sample type are provided. Different datasets involving experiments using the same drug were analyzed and presented separately, since the sample types can be different across datasets. All the P values are computed from differential expression analysis using limma (Ritchie et al, 2015) (Methods). In the boxplots of panels (B) and (D), the center line, box edges and whiskers denotes the median, interquartile range and the rest of the distribution in respective order, except for points that were determined to be outliers using a method that is a function of the interquartile range, as in standard box plots. Abbreviations: HBEC, human primary bronchial epithelial cells.",
    "ncbi_link": "ACE2: 59272
ACE2: 70008
ACE2: 302668"
  },
  {
    "caption": "E) Overexpression of GFP-TDP-43 variants with different mutations that either block (CC and AA mutation, red labels) or mimic phosphorylation (DD and EE, green label) at S403/404 or S409/410 in motor neuron-like NSC-34 cells. Western blot showed a specific signal for total TDP-43 (top panel), TDP-43pS403/404 (middle panel) and TDP-43p409/410 (lower panel) and load control SOD1 (bottom panel).",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "Wild-type mice have small defined crypts in the small intestine with little nuclearβ-catenin at the bottom of the crypt. The small intestine of AhCreERAPCfl/fl, AhCreERCatnblox(ex3)/lox(ex3) (day 5) or AhCreERGsk3alphafl/fl betafl/fl (day 6) show the crypt-progenitor cell (CPC) phenotype with increased crypt size (red bar) and nuclearβ-catenin (arrows) along the crypt-villus axis. Scale bar, 100 μm.",
    "ncbi_link": "AhCre: 
APC: 11789
Catnb: 12387
Gsk3alpha: 606496"
  },
  {
    "caption": "A heterozygous activation of β-catenin (AhCreER Catnblox(ex3)/+) shows no increase in crypt size or nuclear β-catenin at days 5-10. At day 15 post-induction, accumulation of nuclear β-catenin (arrows) becomes evident with a dramatic CPC phenotype at about day 25. Scale bar, 100 μm.",
    "ncbi_link": "AhCre: 
Catnb: 12387"
  },
  {
    "caption": "Culture of small intestinal crypts of WT and VilCreER Apcfl/fl (or AhCreER Apcfl/fl) mice with/without R-spo1 shows the dependence of the Wnt agonist in WT organoids but not in Apc-deficient spheres. Representative photos were taken at day 5 in culture. Black scale bar, 50 μm.",
    "ncbi_link": "AhCre: 
VilCre: 
Apc: 11789"
  },
  {
    "caption": "At day 5 post-induction, only crypts from AhCreERCatnblox(ex3)/lox(ex3) but not AhCreERCatnblox(ex3)/+ survive in culture without the addition of R-spo1. At day 10 post-induction, we observed a mixed phenotype of more organoid-like structures in AhCreERCatnblox(ex3)/+ compared to spheres from Catnblox(ex3)/lox(ex3)crypts in the first week of culture. Black scale bar, 50 μm.",
    "ncbi_link": "AhCre: 
Catnb: 12387"
  },
  {
    "caption": "Table shows that only homozygous activation of β-catenin (Lgr5CreER Catnblox(ex3)/lox(ex3)) or loss of Apc (Lgr5CreER Apcfl/fl) in Lgr5-positive stem cells results in colonic lesions in cohorts, sampled when signs of sickness were apparent. There were no lesions observed when only one allele of β-catenin (Lgr5CreER Catnblox(ex3)/+) was mutated (chi-squared test, P < 0.001).",
    "ncbi_link": "Cre: 
Apc: 11789
Catnb: 12387
β-catenin: 12387
Lgr5: 14160"
  },
  {
    "caption": "qRT-PCR of whole tissue from small intestine and colon. Expression of mRNA (2(−dCt)) calculated relative to GAPDH (N = 3 mice). Statistics: one-sided Mann-Whitney U-test.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Immunoprecipitation (IP) of E-cadherin from VilCreER Catnblox(ex3)/lox(ex3) mice, 24 h (day 1, top) and 48 h (day 2, bottom) after induction. The ratio of wild-type (WT, top lane) and mutant exon 3 β-catenin (Δex3, bottom lane) bound to E-cadherin (IP:Ecad) was calculated for each tissue. Graphs show average of experiments (N = 3 mice for each genotype and time point); error bars represent s.e.m.",
    "ncbi_link": "VilCre: 
Catnb: 12387
β-catenin: 12387"
  },
  {
    "caption": "IP of E-cadherin from VilCreER Catnblox(ex3)/+ mice at day 4 and day 8. Graphs show average of experiments (N = 3 mice for each genotype and time point); error bars represent s.e.m.",
    "ncbi_link": "VilCre: 
Catnb: 12387"
  },
  {
    "caption": "AhCreERCatnblox(ex3)/+ compared to AhCreER Catnblox(ex3)/+ Cdh1fl/+ at day 10 post-induction. Note the presence of colonic lesions in the colon of AhCreER Catnblox(ex3)/+ Cdh1fl/+ mice (arrows). Scale bar, 100 μm; red bar indicates proliferative zone (BrdU).",
    "ncbi_link": "AhCre: 
Cdh1: 12550
Catnb: 12387"
  },
  {
    "caption": "Scoring of BrdU-positive cells per half-crypt in the small intestine of wild-type, AhCreERCdh1fl/+, AhCreERCatnblox(ex3)/+ and AhCreERCatnblox(ex3)/+Cdh1fl/+mice at day 10 post-induction. N ≥ 3, at least 25 crypts per mouse were scored. There was significantly higher proliferation in the AhCreERCatnblox(ex3)/+Cdh1fl/+mice (P = 0.028, one-sided Mann-Whitney U-test).",
    "ncbi_link": "AhCre: 
Cdh1: 12550
Catnb: 12387"
  },
  {
    "caption": "In vitro growth of crypts (small intestine) from mice as indicated at day 5 post-induction without R-spo1. Quantification of sphere-forming efficiency of AhCreERCatnblox(ex3)/+AhCreERCatnblox(ex3)/+Cdh1fl/+, day 5 post-induction. N = 3 mice per genotype, mean of 6 technical replicates per mouse, P = 0.04 one-sided Mann-Whitney U-test.",
    "ncbi_link": "AhCre: 
Cdh1: 12550
Catnb: 12387"
  },
  {
    "caption": "Survival of Lgr5CreERCatnblox(ex3)/+ and Lgr5CreERCatnblox(ex3)/+Cdh1fl/+ shows significant acceleration (P = 0.000123, log-rank test) after E-cadherin reduction. About 85% (6/7 mice) had colonic lesions, as identified with β-cateninIHC in contrast to Lgr5CreERCatnblox(ex3)/+mice.",
    "ncbi_link": "Cre: 
Cdh1: 12550
Catnb: 12387
Lgr5: 14160"
  },
  {
    "caption": "Correlation of several Wnt target genes with the expression of E-cadherin (CDH1) was analysed in 269 HCC patients (TCGA provisional), and linear regression line (blue) and confidence region (shaded) were added.",
    "ncbi_link": "CDH1: 999
E-cadherin: 999"
  },
  {
    "caption": "C, Immunoblot analysis of protein lysates from ARPE-19 cells expressing TFEB-FLAG-WT or mutants treated with 250 μM NaAsO2 or EBSS for 1h and run under non-reducing condition.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "D, Immunoblot analysis of protein lysates from ARPE-19 cells overexpressing TFEB-FLAG or TFE3-MYC, treated with 250 nM Torin-1 for 1 h and run under non-reducing condition. E, Quantification of immunoblot data shown in (D). Data are presented as mean ± SD using two-tailed t-test (*)p<0.05 from three independent experiments. ",
    "ncbi_link": "FLAG: 
MYC: 
TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "D, Relative quantitative RT-PCR analysis of the mRNA expression of autophagy- (UVRAG), mitochondria- (PGC-1α) and lysosome (MCOLN1, ATPV1C1 and HEXA)-related genes in ARPE-19 cells overexpressing TFEB-FLAG-WT or TFEB-FLAG-C212A. Data are presented as mean ± SD using two-way ANOVA, (ns) not significant as compared to the same gene in TFEB-WT overexpressing cells, from three independent experiments.",
    "ncbi_link": "FLAG: 
ATPV1C1: 528
HEXA: 3073
MCOLN1: 57192
PGC-1α: 10891
TFEB: 7942
UVRAG: 7405"
  },
  {
    "caption": "G, Relative quantitative RT-PCR analysis of the mRNA expression of lysosome-related genes (MCOLN1 and ATPV61C1) in ARPE-19 and HeLa cells treated with 100 μM and 50 μM NaAsO2 respectively for the indicated times. Data are presented as mean ± SD using one-way ANOVA (*)p<0.05, (**)p< 0.01, (***)p<0.001 from two independent experiments.",
    "ncbi_link": "ATPV61C1: 528
MCOLN1: 57192"
  },
  {
    "caption": "D, Relative quantitative RT-PCR analysis of the mRNA expression of autophagy- (UVRAG), lysosome- (ATP6V1C1), oxidative stress response- (TXNRD1 and HMOX1), cell cycle control- (CDKN1a) and cytokine production (IL6) -related genes in TFEB/TFE3-double knockout MEFs cells stably expressing TFEB-FLAG-WT or TFEB-FLAG-C212A and treated with 5 μM arsenic trioxide (ATO) or 12.5 μM NaAsO2 for 12 h. Data are presented as mean ± SD using two-way ANOVA (*)p<0.05, (**)p<0.01, (***)p<0.001, and (****)p<0.0001 from three independent experiments.",
    "ncbi_link": "FLAG: 
ATP6V1C1: 66335
CDKN1a: 12575
HMOX1: 15368
IL6: 16193
TFE3: 209446
TFEB: 21425
TXNRD1: 50493
UVRAG: 78610"
  },
  {
    "caption": "C, Representative examples of HLH-30::3xFLAG::eGFP subcellular localization: Cytoplasmic, diffuse GFP distribution along the whole body of the worm; Weak nuclear, some cells in the posterior part of the worm display nuclear GFP labeling but no nuclear labeling is found in the head cells; Strong nuclear, distinct nuclear GFP labeling in cells along the worm body, including neurons in the head area. Arrowheads denote nuclear localization of HLH-30::3xFLAG::eGFP. Scale bar 200 µm and 50 µm. D, Quantification of the subcellular distribution of HLH-30::3xFLAG::eGFP and HLH-30(C284A)::3xFLAG::eGFP upon treatment with different stimuli. Data are from three independent experiments with at least 50 animals per experiment. ",
    "ncbi_link": "eGFP: 
FLAG: 
HLH-30: 177157"
  },
  {
    "caption": "A, Lifespan assay of hlh-30 mutants at 25°C. Graph represents Kaplan-Meier survival plots of two independent experiments initiated with 100 animals per strain. (**)p<0.01 and (****)p<0.0001 by Log-rank (Mantel-Cox) test compared to wild type control. B, Survival of hlh-30 mutants on 7.5 mM NaAsO2. Data are the mean ± SD of three independent experiments initiated with 120 animals per strain. (****)p<0.0001 by two-way ANOVA compared to wild type control. C, Survival of hlh-30 mutants to infection by Staphylococcus aureus. Data are the mean ± SD of three independent experiments initiated with 100 animals per strain. (****)p<0.0001 by two-way ANOVA compared to wild type control. ",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "E, Synthetic developmental delay phenotype of eat-2(ad1116) worms carrying mutations in the hlh-30 gene. Data are the mean ± SD of three independent experiments with at least 20 animals per assay. (****)p<0.0001 by One-way ANOVA with multiple comparison test. F, Representative images of worms quantified in (E). Scale bars 200 µm. ",
    "ncbi_link": "eat-2: 175072
hlh-30: 177157"
  },
  {
    "caption": "Representative fluorescence microscopy images of CD142- ASPCs, co-cultured with CD142+ ASPCs (Aregs) carrying control (scr) or siRNA-mediated knockdowns of selected CD142+ ASPC (Areg)-specific candidate genes: F3, Mgp, and Gdf10 after adipogenic differentiation (i.e., after exposure to an adipogenic cocktail, Methods)",
    "ncbi_link": "F3: 14066
Gdf10: 14560
Mgp: 17313"
  },
  {
    "caption": "Representative fluorescence microscopy images of CD142- ASPCs, co-cultured with CD142+ ASPCs (Aregs) subjected to control (scr) or siRNA-mediated knockdowns of selected RA signalling pathway genes: Rara, Rarb, Rarg, Rbp1, and Rxrg after adipogenic differentiation (i.e., after exposure to an adipogenic cocktail, Methods);   Fraction of differentiated CD142- ASPCs indicated in I, as quantified by the "adiposcore"; marker shapes correspond to different biological replicates, n=24-29, 4 biological replicates, 5-8 independent wells for each.  ",
    "ncbi_link": "Rara: 19401
Rarb: 218772
Rarg: 19411
Rbp1: 19659
Rxrg: 20183"
  },
  {
    "caption": "A. Quantitative real-time PCR analysis of PKCδ mRNA levels in FACS sorted Lin-, LT-HSC, ST-HSC, MPP, L-S-K+, GMP, CMP, MEP and CLP subsets from C56BL/6 wild-type (6-to 9-week old) mice bone marrow. Levels of PKCδ expression were normalized to an internal control gene (β-actin). Expression of PKCδ is shown relative to Lineage negative (Lin-) cells whose expression was arbitrarily set to 1 (n=4 mice analyzed for each population). Data information: All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with Sidak's multiple comparisons test (A)",
    "ncbi_link": "β-actin: 11461
PKCδ: 18753"
  },
  {
    "caption": "(C) Bar charts show the average frequency (left) and absolute number (right) ± SEM of the indicated populations, analyzed from 2 femurs and 2 tibias per mouse (n=10 mice analyzed for each genotype). All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "D. FACS plots show percentages of 'SLAM-code' based stem and progenitor cells in the LSK population. Bar graphs show the average frequency (left) and absolute numbers (right) ± SEM of LT-HSC per 2 femurs and 2 tibias. (n=10 mice analyzed for each genotype). Data information: All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "E. FACS plots illustrate gating and frequencies of myeloid progenitors (MP), granulocyte-monocyte progenitor (GMP), common myeloid progenitor (CMP), and megakaryocyte-erythroid progenitor (MEP) population. Bar graphs show the frequencies (left) and absolute numbers (right) of L-S-K+ MP and GMP, CMP and MEP populations in the BM of WT (n=12) and PKCδ KO (n=12). Data information: All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "F. FACS plots illustrate the gating and percentages of common lymphoid progenitors (CLP). Bar graph shows the absolute number of CLPs per 2 femurs and 2 tibias (n=5 mice for each genotype). Data information: All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "G. FACS plots illustrate the percentages of uncommitted lymphoid progenitors (Lin- IL-7Rα+Flt3+Ly-6D-) and B lymphoid progenitors (BLP). Bar graph represents the average frequencies of CLPs, BLP and uncommitted lymphoid progenitors in total BM (n=5 mice per genotype). Data information: All data are presented as mean±SEM. *p<0.05; **p<0.01, and ***p<0.001 by with one-way ANOVAs with two-tailed Student's unpaired t-test analysis for comparison of WT to PKCδ KO mice.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "H. Limiting dilution analysis (LDA) demonstrates an increased frequency of long-term repopulating HSCs in PKCδ KO BM (solid red lines) compared with WT BM (black solid lines). Engraftment data shown at 14-weeks post-BMT. Plots depict the percentages of recipient mice containing less than 1% CD45.2+ blood nucleated cells. Dotted lines represent the 95% confidence interval of the same (p=0.0005). Data information: All data are presented as mean±SEM. Overall test for differences in stem cell frequencies between WT to PKCδ KO mice was determined with likelihood ratio test of single-hit model (H).",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "A. Representative FACS profiles of HSPC cell cycle analysis using combinatorial staining for Ki67 and Hoechst 33342. Bar charts depict the average percentage of cells in each phase of the cell cycle for each LSK subset from WT (n=6) and PKCδ KO (n=7) mice. Data compiled from two independent experiments. Data information: All data are presented as mean±SEM, *p<0.05 and **p<0.001, with significance determined by two-tailed Student's unpaired t-test analysis.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "B. FACS profiles of indicated BM subsets from WT and PKCδ KO mice 20hr after BrdU injection. Data information: All data are presented as mean±SEM, *p<0.05 and **p<0.001, with significance determined by two-tailed Student's unpaired t-test analysis.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "C. Average percentages of cells in each phase of the cell cycle phases for each of the indicated HSPC subsets from WT and PKCδ KO mice. Data are pooled from two independent experiments (totaling n=6-7 mice per genotype). Data information: All data are presented as mean±SEM, *p<0.05 and **p<0.001, with significance determined by two-tailed Student's unpaired t-test analysis.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "D. Representative FACS plots and summary of FACS data analyzing the frequency of apoptotic HSPC cells using co-staining for AnnexinV and 7-AAD (WT and PKCδ−/− (n=7 per genotype). Data information: All data are presented as mean±SEM, *p<0.05 and **p<0.001, with significance determined by two-tailed Student's unpaired t-test analysis.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "B. Percent of total donor-derived, hematopoietic cells (CD45.2+), B-cells (B220+), myeloid cells (CD11b+Gr1+), and T cells (CD3+) in the peripheral blood (PB) of recipient mice, as determined by FACS at the indicated time points. The statistical significance of differences was determined using two-ANOVAs with Holm-Sidak's multiple comparisons tests (n=8 recipients per genotype in each experiment). Data information: All data are presented as mean±SD. *p<0.05, **p<0.001, with significance determined by repeated measures of two-way ANOVA analysis with Sidak's multiple comparison tests for comparison of recipients of WT and PKCδ KO marrow at each time point and for each cell population.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "C. Percent donor-derived HSPCs in the BM of secondary (left) and tertiary (right) recipients of WT or PKCδ−/− marrow. Data are compiled from two independent experiments (n=8 recipients per genotype). Data information: All data are presented as mean±SD. *p<0.05, **p<0.001, with significance determined by repeated measures of two-way ANOVA analysis with Sidak's multiple comparison tests for comparison of recipients of WT and PKCδ KO marrow at each time point and for each cell population.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "B,C Representative FACS plots of PKCδ fl/fl and cKO BM 4-8 weeks (B), and 20-24-weeks (C) after pIpC treatment. Numbers in plot indicate the absolute numbers of the indicated subset within the gated population (n=8-9 mice per genotype and time point). Data information: Data presented as mean ± SEM. *p<0.05, **p<0.005 and ***p<0.001 by two-tailed Student's unpaired t-test analysis.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "A. MitoStress test revealed increased oxygen consumption rates (OCR) in PKCδ-deleted LSKs. BM LSK cells were sorted from WT and PKCδ cKO mice 12-weeks after pIpC-treatment. OCR was measured at basal level and after sequential loading of ATP synthase inhibitor Oligomycin (350nm), mitochondrial uncoupler, FCCP (10μM), and electron transport chain inhibitor, Rotenone (1μM) using Seahorse XF24 extracellular flux analyzer. Data are from 3 independent experiments (n=9 mice). In each experiment, bone marrow cells from identical genotypes (n=3 mice per genotype) were pooled and used for LSK cell sorting. Data information: The statistical significance of difference was assessed using two-tailed Student's unpaired t-test analysis. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "H. Representative electron microscopy images (4,800x magnification) of control and PKCδ cKO HSPCs. Arrows indicate the mitochondria enriched regions (n=3 mice per genotype). Scale bar represents 500nm.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "I. ROS levels in control and PKCδ cKO HSPCs as measured by FACS based CM-H2DCFDA staining. Bar graph at right shows the relative CM-H2DCFDA MFI. Data compiled from three independent experiments (n=6-8 per genotype). Data information: The statistical significance of difference was assessed using two-tailed Student's unpaired t-test analysis. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Quantitative RT-PCR analysis of selected (A) HSPC transcriptional regulators expression in bone marrow HSPCs (n=4 mice per genotype). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Quantitative RT-PCR analysis of selected (B) cell cycle and apoptosis regulators expression in bone marrow HSPCs (n=4 mice per genotype). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Quantitative RT-PCR analysis of selected (C) known HSPC metabolic regulators expression in bone marrow HSPCs (n=4 mice per genotype). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Intracellular flow cytometry analysis of Cyclin D1 protein (D) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Intracellular flow cytometry analysis of pro-survival regulators Mcl1, Blc2, and Bim protein (E) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "representative FACS histograms and bar graphs show relative levels of pAKT (Ser473) relative to WT controls (F) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "representative FACS histograms and bar graphs show relative levels of pFoxO3a (Ser253) (G) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "representative FACS histograms and bar graphs show relative levels of Total cMyc protein (H) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "; representative FACS histograms and bar graphs show relative levels of pRb (Ser807/811) (I) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "representative FACS histograms and bar graphs show total PPARγ protein levels relative to WT controls (J) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Relative expression levels of total PPARδ protein in HSPCs (K) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Activation of pmTOR (Ser2448) (L) Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Activation of pS6 (Ser235/236) and (Ser240/244) (M). Data shown in bar graphs are mean fluorescence intensity of indicated protein expression in PKCδ cKO HSPCs subsets relative to WT controls (n=4-6 mice per genotype per target). Data information: The statistical significance of difference was assessed using Two-tailed Student's unpaired t-test analysis for comparison of control and PKCδ cKO HSPCs. All data are presented as mean± SEM., *p<0.05, **p<0.001.",
    "ncbi_link": "PKCδ: 18753"
  },
  {
    "caption": "Confocal microscopy reveals typical \"class B\" pattern of βarr1 recruitment for V2R and B2R as reflected by first the localization at the plasma membrane and subsequently, internalization in endosomal vesicles upon agonist-stimulation. HEK-293 cells expressing V2R/B2R and βarr1-mCherry were stimulated with agonist (AVP; 100nM and Bradykinin; 100nM) and the localization of βarr1 was visualized using confocal microscopy. Representative images from three independent experiments are shown here, and the scale bar is 10μm. Visual scoring of images from three independent experiments revealed agonist-induced βarr1 recruitment (i.e. membrane and endosomal localization) in approximately 77% of the cells for V2R (221 cells) and 75% of the cells for B2R (662 cells).",
    "ncbi_link": "βarr1: 408
βarr1: 281637"
  },
  {
    "caption": "Agonist-induced phosphorylation of ERK1/2 in HEK-293 cells expressing either V2R or B2R in the absence (control; CTL) and presence of βarr1 knock-down (βarr1-KD) are measured using Western blotting. Densitometry-based quantification of data (mean ±SEM) from four independent experiments is presented as bar-graphs in the right panels, normalized with respect to maximal signal under control condition (treated as 100%), and analyzed using Two-way-ANOVA with Bonferroni multiple comparisons test (***p<0.001, **p <0.01).",
    "ncbi_link": "βarr1: 408"
  },
  {
    "caption": "Confocal microscopy reveals robust recruitment of βarr1 to B2R mutant constructs upon agonist-stimulation. HEK-293 cells expressing either B2RWT or B2R mutants along with βarr1-mCherry were stimulated with agonist (Bradykinin; 100nM) and the localization of βarr1 was visualized using confocal microscopy. Representative images from three independent experiments are shown here, and the scale bar is 10μm. Visual scoring from three independent experiments revealed agonist-induced βarr1 recruitment (i.e. membrane and endosomal localization) in approximately 75% of the cells for B2RWT (662 cells), 74% of the cells for B2RΔG368 (169 cells), 75% of the cells for B2RL370T (130 cells), 85% of the cells for B2RΔG368+L370T (132 cells) and 77% of the cells for B2RΔI374 (116 cells).",
    "ncbi_link": "βarr1: 281637
B2R: 624"
  },
  {
    "caption": "HEK-293 cells expressing B2R constructs with C-terminal SmBiT and βarr1 with N-terminal LgBiT were treated with indicated concentrations of bradykinin, and ligand-induced change in luminescent signal was measured. Concentration-response curves were plotted using GraphPad Prism, and pEC50 (top) and Emax (bottom) were calculated. Data represent mean ± SEM of five independent experiments (three for B2RΔI374), each performed in duplicate.",
    "ncbi_link": "βarr1: 408
B2R: 624"
  },
  {
    "caption": "Knock-down of βarr1 leads to an increase in agonist-induced ERK1/2 phosphorylation for B2RΔG368 and B2RΔI374 but a decrease for B2RL370T and B2RΔG368+L370T mutants. HEK-293 cells expressing the indicated B2R mutants in presence and absence of βarr1 knock-down were stimulated with indicated doses of bradykinin (Brady) for 10 min followed by detection of phosphorylated ERK1/2 using Western blotting. Densitometry-based quantification of data (mean±SEM) from three independent experiments (five for B2RΔG368 and B2RΔI374) is presented as bar graphs in the lower panels. Data are normalized with respect to maximal signal under control condition (treated as 100%), and analyzed using Two-way-ANOVA with Bonferroni multiple comparisons test (*p <0.05; **p <0.01; ***p<0.001).",
    "ncbi_link": "βarr1: 408
B2R: 624"
  },
  {
    "caption": "HEK-293 cells expressing V2R, B2R, B2RΔG/L370Tor B2RL370T along with βarr1-mCherry and YFP-tagged intrabody30 (Ib30-YFP) were stimulated with their respective agonists (AVP, 100nM for V2R) and (bradykinin, 1μM for B2R) and the localization of βarr1 and Ib30 were visualized. Although βarr1 gets recruited for all four constructs, Ib30-YFP does not colocalize with βarr1 either at the surface or upon internalization in case of B2RWT. Representative data from 3-5 independent experiments are shown and the scale bar is 10μm. Visual scoring from 3-5 independent experiments revealed agonist-induced βarr1 recruitment (i.e. membrane and endosomal localization) in approximately 82% of the cells for V2R (691 cells), 10% for B2RWT (254 cells), 63% for B2RL370T (273 cells) and 83% for B2RΔG368+L370T (158 cells). Pearson's correlation coefficients (PCC) were measured to assess the colocalization of βarr1 and Ib30 using JACoP plugin in ImageJ, and the mean±sem for the basal, surface and internalized panels, respectively, are presented here. B2RWT - 0.32±0.02 from 16 cells, 0.18±0.01 from 32 cells, 0.25±0.02 from 31 cells; B2RΔG/L370T - 0.32±0.03 from 13 cells, 0.92±0.01 from 18 cells, 0.90±0.01 from 16 cells; B2RL370T - 0.26±0.01 from 10 cells, 0.85±0.01 from 11 cells, 0.87±0.01 from 25 cells.",
    "ncbi_link": "V2R: 554
B2R: 624"
  },
  {
    "caption": "HEK-293 cells expressing the NanoBiT-Gq protein and indicated B2R constructs were treated different concentrations of bradykinin, and ligand-induced change in luminescent signal was measured. Concentration-response curves were plotted using GraphPad Prism to calculate pEC50 (top) and Emax(bottom) values included in the graph. Data represent mean±SEM of three independent experiments with each performed in duplicate, and normalized with respect to the luminescence signal under basal (no-agonist treatment) condition (treated as 1).",
    "ncbi_link": "B2R: 624"
  },
  {
    "caption": "HEK-293 cells expressing the indicated AT1aR constructs, in absence (CTL; control) or presence of βarr1 knock-down (βarr1-KD) were stimulated with indicated concentrations of angiotensin II (AngII) for 10 min. Subsequently, ERK1/2 phosphorylation was measured by Western blotting and signal intensities were quantified using densitometry and presented as bar graphs. Data were normalized with respect to the signal at 100nM agonist concentration in control cells (treated as 100%) and represent mean±SEM of five independent experiments. Data were analyzed using Two-way-ANOVA with Bonferroni multiple comparisons test (***p<0.001, p<0.05).",
    "ncbi_link": "AT1aR: 185
βarr1: 408"
  },
  {
    "caption": "HEK-293 cells expressing the indicated AT1aR constructs, in absence (CTL; control) or presence of βarr1 knock-down (βarr1-KD) were stimulated with indicated concentrations of angiotensin II (AngII) for 10 min. Subsequently, ERK1/2 phosphorylation was measured by Western blotting and signal intensities were quantified using densitometry and presented as bar graphs. Data were normalized with respect to the signal at 100nM agonist concentration in control cells (treated as 100%) and represent mean±SEM of five (six for AT1aRΔL337) independent experiments. Data were analyzed using Two-way-ANOVA with Bonferroni multiple comparisons test (***p<0.001, p<0.05).",
    "ncbi_link": "AT1aR: 185
βarr1: 408"
  },
  {
    "caption": "D. Temporal dynamics of ALKAL2-induced transcription of ARC, EGR1-3, FOS and FOSB in NB1 and IMR32 cells in the presence and absence of the lorlatinib, as indicated.",
    "ncbi_link": "ARC: 23237
EGR1: 1958
FOS: 2353
FOSB: 2354"
  },
  {
    "caption": "D. Kaplan-Meier survival curve of mice resulting from intercrosses of Th-MYCN hemizygotes and Alk-F1178S heterozygote mice (p<0.0001; log-rank test). Wild type littermates were excluded.",
    "ncbi_link": "Alk: 11682
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "E. Gross appearance, hematoxylin and eosin as well as Ki67 stained sections of representative Th-MYCN and Alk-F1178S;Th-MYCN tumours. Scale bars indicate 250μm.",
    "ncbi_link": "Alk: 11682
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "A. The oncogenic activity of MYCN is potentiated by overexpression of ALKAL2. Kaplan-Meier survival curves for Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN mice. Also shown are Rosa26_Alkal2N, Alk-F1178S and control (Ctrl) mice. Comparison of survival of Th-MYCN alone and Rosa26_Alkal2;Th-MYCN curves showed a significant difference (p=0.003; log-rank test).",
    "ncbi_link": "Alk: 11682
ALKAL2: 100294583
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "Tumours harvested from Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN mice express NB markers. Tumours from all three genotypes were large, in most cases filling the abdominal cavity (B).",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "Dissection post-mortem revealed that the majority of Rosa26_Alkal2;Th-MYCN (18/20) and Alk-F1178S;Th-MYCN (7/10) tumours did not involve the adrenal glands (C).",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "Histological examination of Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN tumours revealed positive staining for NCAM1, synaptophysin (SYP) and Chromogranin A (CGA). Scale bars indicate 100μm. (D)",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "Histological examination of Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN tumours was confirmed for NCAM1 and SYP along with MYCN, ALK and ALKAL2 by immunoblotting (E). Immunoblots are representative of 3 independent technical analyses.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "F. Accumulated Kaplan-Meier survival curves are shown for all monitored Rosa26_Alkal2;Th-MYCN, Alk-F1178S;Th-MYCN and Th-MYCN mice over time, estimating tumour penetrance (p<0.001; log-rank test).",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "RNA-Seq based differential gene expression analysis of tumours arising in Rosa26_Alkal2;Th-MYCN (Alkal2) [n=6], Alk-F1178S;Th-MYCN (AlkF1174S) [n=6] and Th-MYCN (MYCN) mice [n=4]. See Table S4 for detailed results. A. Read coverage of the codon-optimised Alkal2 transgene, confirming Alkal2 expression in Alkal2 tumours. ",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "C-D. Volcano plot showing differential expression (DE) between Alkal2 and MYCN tumours. Differentially expressed genes are shown in blue (DE in Alkal2 tumours only) or black (DE in both Alkal2 and AlkF1174S tumours, as shown in (D)). Top ranked genes labelled. Dashed lines represent DE cut-offs.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
MYCN: 4613"
  },
  {
    "caption": "F. Boxplot showing Vgf expression in the 3 tumour types as indicated. Box plots indicate median values and lower/upper quartiles with whiskers extending to 1.5 times the interquartile range. P values calculated using Wald test as reported by DESeq2.",
    "ncbi_link": "Vgf: 381677"
  },
  {
    "caption": "G. Histological examination of Th-MYCN, Rosa26_Alkal2;Th-null and Alk-F1178S;Th-MYCN tumours revealing positive staining for VGF. Scale bars indicate 100μm.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "Murine NB cell lines were generated from tumours arising in Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456) mice. A. Alkal2 expression in cells derived from Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456) NB. Immunoblotting analysis for ALKAL2 and tubulin in the indicated mouse NB cell lines. Whole cell lysates (30μg) were analysed in each lane. ",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "B. The effect of increasing concentrations of brigatintib on cell confluence was analyzed by IncuCyte Live Cell Analysis of both Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456) cell lines. Data is presented as mean ± SEM from three independent experiments. *p<0.05, **p<0.005; two-tailed paired student t-test.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "E. Tumour spheroids formed from either Rosa26_Alkal2;Th-MYCN (#3540) or Alk-F1178S;Th-MYCN (#3456) were formed at indicated cell number in ultra-low attachment plates for 3d and followed by brigatinib (0, 150nM) for 10d. Inhibitor was re-fed every other day. Cell viability was determined by CellTiter-Glo 3D cell viability kit and data is presented as mean ± SEM from five independent experiments. *p<0.05, ****p<0.0001, two-tailed unpaired student t-test.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "F. Cell viability. Mouse tumour derived cell lines #3540 (Rosa26_Alkal2;Th-MYCN) and #3456 (Alk-F1178S;Th-MYCN) were treated with brigatinib (125nM and 500nM) and viability was evaluated by using a resazurin-based assay. Data is presented as mean ± SEM from three independent experiments. *p<0.05, **p<0.005; two-tailed paired student t-test.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "G. Brigatinib treatment (0 or 150 nM) for 6h resulted in inhibition of ALK phosphorylation, and of activation of downstream signaling (ERK1/2), as well as MYCN expression. Cell lysates (Rosa26_Alkal2;Th-MYCN (#3540) and Alk-F1178S;Th-MYCN (#3456)) were immunoblotted with the indicated antibodies.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "A. Cells derived from tumours arising in Rosa26_Alkal2;Th-MYCN (#4953) and Alk-F1178S;Th-MYCN (#4938) mice are sensitive to both lorlatinib and brigatinib. The effect of increasing concentrations of each ALK TKI (as indicated) on cell confluence was analyzed by IncuCyte Live Cell Analysis. Data is presented as mean ± SEM from three independent experiments. *p<0.05, **p<0.005; two-tailed paired student t-test.",
    "ncbi_link": "Alk: 11682
Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "B. Tumour volume changes over time for Rosa26_Alkal2;Th-MYCN mice treated with lorlatinib (10 mg/kg; twice daily) or vehicle control. Tumour volume was measured by ultrasound on Day 0 and 7, and by direct measurement at Day 14. Day 0 (lorlatinib n=7, Ctrl n=6), Day 7 (lorlatinib n=2, Ctrl n=5) and Day 14 (lorlatinib n=7, Ctrl n=6). Data shown represents mean ± SD. **p<0.005; two-tailed unpaired student t-test.",
    "ncbi_link": "Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "C. Rosa26_Alkal2;Th-MYCN animals treated with lorlatinib did not display any significant loss of body weight compared with vehicle controls. Data shown represents mean ± SD.",
    "ncbi_link": "Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "D. Representative ultrasound images of tumours observed in Rosa26_Alkal2;Th-MYCN mice with annotated measurements at Day 0 and Day 7. Tumours arise in the retroperitoneal space ventral to the aorta, Ao.",
    "ncbi_link": "Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "E. Representative MRI imaging of Rosa26_Alkal2;Th-MYCN tumours in response to lorlatinib at 4d and 14d.",
    "ncbi_link": "Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "F. Rosa26_Alkal2;Th-MYCN tumours from lorlatinib or vehicle controls were analysed for pHis. A representative field of view for each tumour at 40x (175740μm2) were manually counted. Data shown represents mean ± 95% CI. p=0.0286; Mann-Whitney test.",
    "ncbi_link": "Alkal2: 100294583
Rosa26: 14910
MYCN: 4613
Th: 25085"
  },
  {
    "caption": "B. The BZLF1 m6A levels were measured using MeRIP-qPCR in CNE2EBV, Raji and B95-8 cells with latent EBV infection or lytic reactivation. TPA (30 ng/ml) and NaB (2 mM) were used to treat the cells for 24 h to reactivate EBV. The cellular RNA was harvested for MeRIP-qPCR assays. The fold enrichment was determined by calculating the 2-ΔCt of the MeRIP sample relative to the input sample. The mean value of the results in mock-treated cells was normalized to 1.",
    "ncbi_link": "BZLF1: 3783744"
  },
  {
    "caption": "M. The relative EBV production in C666 cells transfected with YTHDF1-specific siRNAs (siY1-1 and siY1-2) or the siNC control was measured by qPCR. The DNA from the cell-free culture supernatant was harvested at 24 h after siRNA transfection. The number of EBV copies in the supernatant of the cells was quantified by qPCR using specific primers targeting BamHI-W fragment region of EBV. The mean value of EBV copies in the siNC cells was normalized to 1.",
    "ncbi_link": "Y1: 54915
YTHDF1: 54915"
  },
  {
    "caption": "B. The relative mRNA levels of BZLF1 and BRLF1 in the latently infected or reactivated (24 h post NaB treatment) CNE2EBV cells transfected with the YTHDF1-specific siRNAs (siY1-1 and siY1-2) or the siNC control. After 24 h of siRNA transfection, CNE2EBV cells were treated with NaB (2 mM) or mock for 24 h, followed by qRT-PCR analysis. All the gene expression levels were normalized to the housekeeping gene ACTB.",
    "ncbi_link": "ACTB: 
BRLF1: 3783727
BZLF1: 3783744
Y1: 54915
YTHDF1: 54915"
  },
  {
    "caption": "D. The relative enrichment of the BZLF1 and BRLF1 mRNA in CNE2EBV cells with transfected with siYTHDF2, siYTHDF3 or siNC siRNA following EBV reactivation. After 24 h of siRNA transfection, CNE2EBV cells were treated with TPA (30 ng/ml) and NaB (2 mM) for 24 h. The RIP assays were performed using YTHDF1-specific antibody or IgG control in these cells. Fold enrichment was determined by calculating the 2-ΔCt of the RIP sample relative to the input sample.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744
YTHDF2: 51441
YTHDF3: 253943"
  },
  {
    "caption": "E, F. The relative m6A and YTHDF1 enrichment of the BZLF1 (E) or BRLF1 (F) mRNAs measured in CNE2EBV cells transfected with the METTL14-specific siRNAs (siM14) or siNC control following EBV reactivation. After 24 h of siRNA transfection, CNE2EBV cells were treated with TPA (30 ng/ml) and NaB (2 mM) for 24 h, followed by MeRIP and RIP assays. The fold enrichment was determined by calculating the 2-ΔCt of the RIP sample relative to the input sample.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744
M14: 57721
METTL14: 57721"
  },
  {
    "caption": "F. The interactions between endogenous YTHDF1 and ZAP, DDX17 or DCP2 were detected by endogenous IP assays in CNE2EBV cells transfected with YTHDF2-, YTHDF3-specific siRNAs or the siNC control. YTHDF1, YTHDF2, YTHDF3, ZAP, DDX17, and DCP2 were detected in the immunoprecipitated complexes using specific antibodies, respectively.",
    "ncbi_link": "YTHDF2: 51441
YTHDF3: 253943"
  },
  {
    "caption": "F. The relative mRNA levels of BZLF1 and BRLF1 in C666 cells transfected with YTHDF1-specific siRNAs and XRN1-specific siRNAs. The C666 cells were co-transfected with YTHDF1-specific siRNAs and XRN1-specific siRNAs for 24 h. The mRNA levels were determined using qPCR.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744
XRN1: 54464
YTHDF1: 54915"
  },
  {
    "caption": "G. The relative enrichment of BZLF1 and BRLF1 mRNAs by ZAP, DDX17, or DCP2 in CNE2EBV cells following EBV reactivation. CNE2EBV cells were transfected with plasmids encoding myc-ZAP, myc-DDX17, myc-DCP2, or vector control. At 24 h post transfection, the cells were treated with TPA (30 ng/ml) and NaB (2 mM) for 24 h. The RIP assays were performed using Myc-beads. The fold enrichment was determined by calculating the 2-ΔCt of the RIP sample relative to the input sample.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744
DCP2: 167227
DDX17: 10521
ZAP: 56829"
  },
  {
    "caption": "H. Determination of the EBV infection efficiency in HK1 cells transfected with the XRN1-specific siRNA or the siNC control. After 24 h of siRNA transfection, HK1 cells were infected with EBV and analyzed by FACS at 24 hpi.",
    "ncbi_link": "XRN1: 54464"
  },
  {
    "caption": "A. Maximum intensity projections across Z stacks of example images from indicated mESCs stained for L1 Tf RNA (red) combined with immunostaining for L1 ORF1p (green) and nuclei stained with DAPI (blue). The grey square marks position of the inset. White arrow heads point to cytoplasmic foci where L1 RNA and ORF1p co-localize. Scatter plot shows the number of co-localized L1 Tf-ORF1 foci in the cytoplasm per cell (n=275 WT, 304 Dicer_KO1, 311 Dicer_KO2 cells). Red arrow heads point to relatively larger sized L1 RNP foci. Bar graphs are mean values of percentage of cells with large L1 Tf-ORF1 foci co-localizing in the cytoplasm (n=3 technical replicates).",
    "ncbi_link": "Dicer: 192119
L1: 381591"
  },
  {
    "caption": "B. Maximum intensity projections across Z stacks of example images from indicated mESCs immunostained for L1 ORF1p (red), MOV10 (green) and nuclei stained with DAPI (blue). The grey square marks position of inset in the zoomed image. White arrow heads point to cytoplasmic foci where L1 ORF1p and MOV10 co-localize. Scatter plot shows the number of co-localized ORF1-MOV10 foci in the cytoplasm per cell (n= 293 WT, 295 Dicer_KO1, 295 Dicer_KO2 cells). Red arrow heads point to relatively larger sized L1 ORF1-MOV10 foci. Bar graphs are mean values of percentage of cells with large ORF1-MOV10 foci co-localizing in the cytoplasm (n=3 technical replicates).",
    "ncbi_link": "Dicer: 192119"
  },
  {
    "caption": "A. WT and Dicer_KO mESCs were treated with 0.5mM Sodium Arsenite (NaAsO2) for 20 minutes or left untreated prior to fixation with formaldehyde. Maximum intensity projections across Z stacks of example images from indicated mESCs immunostained for G3BP1 (red) and MOV10 (green) with nuclei stained with DAPI (blue).",
    "ncbi_link": "Dicer: 192119"
  },
  {
    "caption": "B. Representative western blots showing low AGO2 protein levels in Dicer_KO as compared to WT mESCs (right side). LAMINB1 served as loading control. On the left, maximum intensity projections across Z stacks of example images from indicated mESCs stained for L1 Tf RNA FISH (red) combined with immunostaining for a resident protein of P-bodies, DDX6 (green) and nuclei stained with DAPI (blue). The grey square marks position of the inset. Yellow arrow heads point to cytoplasmic foci where L1 RNA and DDX6 protein co-localize.",
    "ncbi_link": "Dicer: 192119
L1: 381591"
  },
  {
    "caption": "B. Maximum intensity projections across Z stacks of example images from indicated mESCs immunostained for L1 ORF1p (green) combined with RNA FISH for L1 Tf RNA (red) and nuclei stained with DAPI (blue) (n=3 technical replicates).",
    "ncbi_link": "L1: 381591"
  },
  {
    "caption": "C. Representative images of BlastR colonies stained with crystal violet blue of indicated cell lines is shown on the left. Cells were transfected with either mutant reporter plasmid (L1N21A) or retrotransposition competent reporter (L1WT) as shown in the scheme with timeline for the experiment on the top. Bar graphs on the right depict the average number of BlastR colonies (n=3 biological replicates).",
    "ncbi_link": "L1: 381591"
  },
  {
    "caption": "A. Scheme and quantification of relative luminescence from luciferase assays validating post-transcriptional regulation of MOV10 by miRNAs in HEK293T cells (n=4 biological replicates).",
    "ncbi_link": "MOV10: 17454"
  },
  {
    "caption": "B. Scheme and quantification of relative luminescence from luciferase assays in Hek293T cells to confirm specificity of post-transcriptional regulation of MOV10 by miRNAs with either wild-type (WT) or Mutant (MUT) reporters where the MicroRNA Response Element (MRE) for the depicted miRNAs in the 3'UTR of MOV10 were mutated (n=3 biological replicates).",
    "ncbi_link": "MOV10: 4343"
  },
  {
    "caption": "D. Scheme and representative images from colony forming assays for plasmid based retrotransposition analysis where miRNA mediated downregulation of MOV10 in Drosha_KO mESCs is accompanied by an increase in L1 retrotransposition (n=3 biological replicates).",
    "ncbi_link": "Drosha: 14000
L1: 381591
MOV10: 17454"
  },
  {
    "caption": "A. Scheme of experiment and representative images along with quantitation showing induction of L1 RNP aggregate formation upon ectopic MOV10 expression. Images are maximum intensity projections across Z stacks from indicated mESCs stained for L1 ORF1p (red) combined with immunostaining for HA (green) to detect ectopically expressed MOV10 tagged with HA, and nuclei stained with DAPI (blue). White arrow heads point to cytoplasmic foci where L1 ORF1p and HA-MOV10 co-localize. Data collected from 289 Ctrl, 275 L1UP Cl1 and 296 L1UP Cl2 mESCs (n=3 biological replicates).",
    "ncbi_link": "L1: 381591
MOV10: 4343"
  },
  {
    "caption": "B. Scheme and representative images from colony forming assays for plasmid based retrotransposition analysis in Ctrl and L1UP mESCs comparing rate of retrotransposition upon transfection with Empty Vector (EV) or ectopic expression of HA-MOV10 (n=3 biological replicates).",
    "ncbi_link": "HA: 
L1: 381591
MOV10: 4343"
  },
  {
    "caption": "A. Scheme of experiment and representative images showing RNP aggregate formation upon ectopic expression of full length L1 and HA-MOV10 in WT mESCs. Images are maximum intensity projections across Z stacks stained for L1 ORF1p (red) combined with immunostaining for HA (green) to detect ectopically expressed MOV10, and nuclei stained with DAPI (blue). The bottom panel shows cells where accumulation of ORF1-MOV10 was observed in relatively large foci compared to cells where co-localization of the two proteins was mostly in relatively small foci (top panel), 68-119 transfected cells were analyzed per experiment (n=3 biological replicates).",
    "ncbi_link": "HA: 
L1: 54596
MOV10: 4343"
  },
  {
    "caption": "B. Scheme of experiment and representative images showing RNP aggregate formation upon ectopic expression of HA-ORF1 or HA-ORF1 in conjunction with T7-MOV10 in WT mESCs. Images are maximum intensity projections across Z stacks stained for HA (green) and T7 (red) to detect ectopically expressed ORF1p and MOV10 respectively, and nuclei stained with DAPI (blue). 100-147 transfected cells were analyzed per experiment (n=3 biological replicates).",
    "ncbi_link": "HA: 
T7: 
ORF1: 54596
MOV10: 4343"
  },
  {
    "caption": "A. Representative  western blot of two matched pairs of control (Ctrl) and FBXL4  KO pool RPE1-Cas9i-mt-mKeima  cells, generated with two distinct sgRNAs. B. Quantification of data represented in A. Individual datapoints from n=3 independent colour coded experiments are shown. Error bars show standard deviation of the fold change in BNIP3  and NIX  in each KO pool normalised to their matched control pools; one-way ANOVA and Tukey's multiple comparison's test, **P<0.01, ****P<0.0001.",
    "ncbi_link": "mKeima: 
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "D. Representative images of control or FBXL4  KO pool RPE1-Cas9i-mt-mKeima  cells. \"Magenta only\" puncta (Ex. 561) correspond to acidic mitolysosomes. Scale bar 20 µm. E. Graphs show the quantification of mitolysosomes  (mt-mkeima  \"magenta only\" puncta) per cell. A minimum of 45 cells were analysed per condition in each experiment. Individual data from two (for control 1 (Ctrl 1) and knockout 1 (KO1)) or three (control 2 (Ctrl 2) and knockout 2 (KO2)) are shown using different colours for each independent experiment. Mean and standard deviation are indicated. Bottom graph shows the individual data points. One-way ANOVA with Tukey's multiple comparison's test, *P<0.05.",
    "ncbi_link": "mKeima: 
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "G. Quantitative RT-PCR reactions of BNIP3  and NIX  (normalised to Actin) were performed with cDNA derived from control and FBXL4  KO RPE1-Cas9i-mt-mKeima  cells. Two primer pairs were used per target indicated by symbol shape. Three independent colour-coded experiments are shown. Error bars show standard deviation of the fold change of BNIP3  and NIX  mRNA in each KO pool normalised to their matched control pools.",
    "ncbi_link": "mKeima: 
Actin: 60
BNIP3: 664
NIX: 665
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "A and B. hTERT-RPE1  cells were co-transfected with Flag  (V) or FBXL4-Flag  (FL4) and either GFP  (Vect), GFP-BNIP3  or GFP-NIX. Lysates were subjected to immunoprecipitation  (IP) with either GFP-nanobody coupled beads (A) or Flag-antibody coupled agarose  beads (B). IPs  were probed alongside the input samples for Flag  and GFP.",
    "ncbi_link": "Flag: 
GFP: 
NIX: 
BNIP3: 664
FBXL4: 26235"
  },
  {
    "caption": "D. hTERT-RPE1 cells were transfected with empty vector (V), FBXL4-Flag  (WT) or FBXL4- R482W-Flag  (RW). Lysates were subjected to IP  with Flag-antibody coupled agarose  beads and probed for SKP1  and Flag. Note that FBXL4-Flag  presents with an as yet uncharacterized higher molecular weight band (indicated by a blue arrowhead) E. Quantitation of SKP1  protein co-immunoprecipitated with FBXL4-R482W-Flag   relative to FBXL4-Flag   (WT). Data from two independent experiments are shown, normalised to the amount of SKP1  in the input and the FBXL4-Flag  in the IP.",
    "ncbi_link": "Flag: 
FBXL4: 26235"
  },
  {
    "caption": "F and G. Representative images of Control (Ctrl) and FBXL4  KO RPE1-Cas9i-mt-mKeima  cells transfected with FBXL4-Flag  wild-type (WT) or FBXL4-Flag  [R482W] for 24 hours, then fixed and stained  for either BNIP3  or NIX. Scale bar 20 µm. Quantitation of the frequency of high BNIP3 and high NIX  phenotypes observed in F and G. A minimum of 32 Flag-positive (Transfected, indicated by an asterisk in the images) and Flag-negative cells were analysed per condition in each experiment. Shown are the mean and individual datapoints of two colour-coded experiments.",
    "ncbi_link": "Flag: 
mKeima: 
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "Control (Ctrl) or FBXL4  KO RPE1-Cas9i-mt-mkeima  cells were treated for 72 hours with either non-targeting (NT1), BNIP3  (B3), NIX  or HIF1α  (HIF) siRNA. A. Representative images of the mt-mKeima  reporter in Control (Ctrl2) or FBXL4  KO2 RPE1-Cas9i-mt-mkeima. \"Magenta only\" puncta (Ex. 561) correspond to acidic mitolysosomes. Scale bar: 20 µm.",
    "ncbi_link": "mkeima: 
B3: 664
BNIP3: 664
NIX: 665
Cas9: 69900935
FBXL4: 26235
HIF: 3091
HIF1α: 3091"
  },
  {
    "caption": "C. Representative western blot  of lysates prepared from  hTERT-RPE1  cells transfected with siRNA targeting BNIP3  (B3), NIX  or both for 72 hours. Cells were treated with either DMSO  or MLN4924  (1 µM) for the last 24 hours of transfection. Untransfected cells were treated alongside transfected ones with DMSO, antimycin  and oligomycin  (AO; 1 and 10 µM respectively), or MLN4924. D. Quantification of fold change in protein levels calculated from data represented in C for three colour-coded independent experiments; One way ANOVA and Dunnett's multiple comparison test *P<0.05, ****P<0.0001.",
    "ncbi_link": "B3: 664
BNIP3: 664
NIX: 665"
  },
  {
    "caption": "A. Representative western blot  of lysates from control or FBXL4  KO RPE1-Cas9i-mt-mKeima  cells treated with MLN4924  (1 µM) for 6 hours. B. Representative western blot of lysates from control or FBXL4  KO RPE1-Cas9i-mt-mKeima  cells pre-treated without or with MLN4924  (1 µM) for 6 hours followed by a cycloheximide  (CHX) chase (100 µg/ml).",
    "ncbi_link": "mKeima: 
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "F. TUBES-pulldown  of ubiquitylated NIX. FBXL4  KO RPE1-Cas9i-mt-mkeima  cells and matched control cells were treated as in E and lysates subjected to a TUBES pulldown.",
    "ncbi_link": "mkeima: 
Cas9: 69900935
FBXL4: 26235"
  },
  {
    "caption": "Inhibition of cell fusion by ACE2-Ig.Potent inhibition of cell fusion mediated by the SARS-CoV (left) or 2019 nCoV (right) spike (S) glycoprotein. Cells expressing diffferent S glycoprotein were incubated with indicated fusion proteins and mixed with ACE2-expressing cells. The activity of the reporter gene, β-gal, was measured as a correlate of fusion. The curves represent the best fit to the experimental data and were used for calculation of the IC50. Bars indicate the S.E.",
    "ncbi_link": "β-gal: 
ACE2: 59272"
  },
  {
    "caption": "(C) Co-immunoprecipitation using BmN4 cells transfected with the Flag-tagged DEAD-box helicases identified by shotgun proteomics. The Flag-tagged proteins and Ago3 were detected by western blotting. Full-length Flag-tagged proteins are indicated with red asterisks. h.c.: heavy chain.",
    "ncbi_link": "Flag: "
  },
  {
    "caption": "(F, G) Analysis of Siwi-piRNA and Ago3-piRNA levels in Siwi and Ago3 complexes with DDX43, respectively. The WB (western blotting) and NB (northern blotting) signals represent the PIWI protein and piRNA levels, respectively (see also Figs EV1A and EV1B). The relative ratios of piRISC were calculated based on the signal intensities of the PIWI proteins and piRNAs.",
    "ncbi_link": "Ago3: 100125337
Siwi: 100125336"
  },
  {
    "caption": "(C, D) Immunoprecipitation of endogenous Siwi, DDX43, and Vret bound with Ago3 from DDX43-depleted (C) or Vret-depleted (D) cells. The factors were detected by western blotting. Ago3 interacts with Vret and DDX43 independently of the other.",
    "ncbi_link": "DDX43: 101735665
Vret: 101739668"
  },
  {
    "caption": "(C) Immunoprecipitation of Ago3 with Flag-tagged DDX43 WT and its D399A and E400Q mutants. Ago3 and DDX43 were detected by western blotting using anti-Ago3 and anti-Flag-antibodies, respectively. Flag-EGFP was used as a negative control. The E400Q mutation in DDX43 impairs the interaction between Ago3 and DDX43. IgG h.c.: IgG heavy chain.",
    "ncbi_link": "Flag: 
DDX43: 101735665"
  },
  {
    "caption": "(F) RNA unwinding assays upon Ago3-piRISC-dependent target RNA cleavage. Unwinding activities of DDX43 WT and its D399A, E400Q, and ∆KH mutants are shown. RNAs cleaved by Ago3 are shown as \"Cleaved RNA\".",
    "ncbi_link": "DDX43: 101735665"
  },
  {
    "caption": "B In vivo transduction profile of luciferase reporter vectors displaying variants of the enriched library capsid sequence motifs or unmodified wild type AAV2 control capsid. Four weeks after i.v. injection of 5x1010 genomic particles/mouse containing a CMV-luciferase reporter gene, luminescence was measured in the brain and control organs. Data are shown as bars (mean) with plotted individual data points (n = 3 animals/group, age 8-12 weeks).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "A Luciferase reporter gene vectors displaying the brain-targeted peptide NRGTEWD (\"BR1\"), unmodified wild type AAV2 capsid, or the previously reported brain-targeting peptide DSPAHPS (PPS). Vectors were intravenously injected into mice (5x1010 genomic particles/mouse). Panels show representative examples of n = 5 animals, age 8-12 weeks per group. Animals were imaged in dorsal (left panel), ventral (second from left panel), and lateral (second from right and right panel) position, 14 days after vector injection.B Close-up imaging of AAV-BR1-treated mice. Mice were imaged in dorsal and lateral position in a different color scheme allowing detailed visualization of the transduced brain in living animals, even as late as at day 264 after vector injection.C Virtual sections : sagittal, coronal, and transaxial (left panels) and three-dimensional reconstruction (right panel) of the luminescence images of a mouse injected with BR1 vector (as in A). Images were obtained by measuring different wavelengths of the emitted light (Living Image software), confirming the brain as exclusive source of luminescence.",
    "ncbi_link": "Luciferase: "
  },
  {
    "caption": "AAV-BR1 vector harboring the luciferase gene under control of the CAG promoter was administered intravenously (5x1010 genomic particles/mouse, age 8 weeks). Long-term transgene expression was analyzed by in vivo bioluminescence imaging at 16 time points during a 665-day period (n = 2 animals). Original images of analyzed animals (above) and quantification of luminescence in the brain as the region of interest = ROI (bottom).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "Luciferase activity and vector copy numbers were determined in tissue lysates 14 days after vector administration (5x1010 genomic particles/mouse, age 8-12 weeks).A Vector-mediated luminescence. Transgene expression was measured in AAV-BR1 harboring the luciferase gene under control of the CAG promoter and control vectors (AAV-PPS and wild type rAAV2) in brain and off-target control organs (left panel). Comparison of luminescence in the brain mediated by AAV-BR1 and control vectors (right panel), ****p < 0.0001 (BR1: brain vs. all), ***p = 0.0002 (PPS: heart vs. brain/ muscle), ***p = 0.0001 (PPS: heart vs. lung/ liver/ spleen/ kidney), *p = 0.0101 (WT: heart vs. lung), *p = 0.0120 (WT: heart vs. spleen), *p = 0.0148 (WT: heart vs. kidney), *p = 0.0113 (WT: heart vs. muscle), **p = 0.0011 (Brain: BR1 vs. PPS), ***p = 0.0009 (Brain: BR1 vs. WT).",
    "ncbi_link": "Luciferase: 
luciferase: "
  },
  {
    "caption": "Two weeks after vector injection (1.8 x1011 genomic particles/ animal), into 16-weeks old mice, Cre-mediated gene recombination driven by the CAG promoter was observed mainly in brain endothelial cells (lower panel, red). No recombination was observed in control animals without BR1-iCre-virus injection (upper panel). CD31 (green) was used as a marker for brain endothelial cells. Panels show representative examples of n = 3 animals. Scale bars represent 250 µm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter.A Immunostaining of cerebral microvessels. Treatment with AAV-BR1-NEMO normalized string vessels (white arrows, highlighted in white square inset) in Nemo-/+ mice as compared to Nemo-/+ mice treated with the AAV-BR1-eGFP control vector at postnatal day 8 (P8). The upper left panel shows the staining in untreated wild type control mice. String vessels were identified as capillaries that have lost CD31-positive (green) endothelial cells but stain for the basement membrane protein collagen IV (red). Scale bars represent 200 µm. The lower right panel summarizes quantitative analysis of string vessels in Nemo-/+ and control mice (NemoFl or wild type) at P0 (n=3 animals/ group) and at P8 (n=6 animals/ group, *p = 0.0125). String vessels in the cerebral cortex were quantified as percentage of total vessel lengths.",
    "ncbi_link": "Nemo: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter.B Quantification of active caspase 3-positive endothelial cells at P8 (n= 5 animals/ group, *p = 0.0201).",
    "ncbi_link": "NEMO: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter.C Albumin in brain tissue as indicator for BBB leakage. In Nemo-/+ mice treated with AAV-BR1-NEMO, less albumin was found in brain tissue, indicating less BBB leakage. Representative Western blot with albumin from P8 Nemo-/+ mice treated with AAV-BR1-NEMO or AAV-BR1-eGFP control vector, respectively, as well as untreated wild type (WT) control mice. Right panel: quantitative analysis of the Western blots (n = 4 animals/ group, *p = 0.0283)",
    "ncbi_link": "NEMO: 16151
Nemo: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter.D Body weight of vector-treated mice. WT control or Nemo-/+ mice at P8 treated with AAV-BR1-NEMO or AAV-BR1-eGFP (n= 18 animals/ group, *p = 0.0038).",
    "ncbi_link": "Nemo: 16151
NEMO: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter. All animals were at the age of 8-12 weeks.A Representative immunostainings of cerebral microvessels. String vessels (white arrows, highlighted in white square inset) were significantly reduced in NemobeKO mice treated with AAV-BR1-NEMO compared to NemobeKO mice treated with AAV-BR1-eGFP control vector. NemoFl mice served as control animals. Scale bars represent 200 µm.B Quantification of string vessel lengths in the cerebral cortex as percentage of total vessel lengths. NemobeKO and NemoFl mice were treated with AAV-BR1-NEMO or AAV-BR1-eGFP control vector (n=9 NemoFl animals + BR1-eGFP, 10 NemobeKO animals + BR1-eGFP, 9 NemoFl animals + BR1-NEMO, and 13 NemobeKO animals + BR1-NEMO), ****p < 0.0001.C Total vessel length measured as total CD31-positive vessels. Vessels were restored in NemobeKO mice treated with AAV-BR1-NEMO compared to the AAV-BR1-eGFP injected mice. NemoFl mice served as a control (n= 9 NemoFl animals +BR1-eGFP, 10 NemobeKO animals + BR1-eGFP, 9 NemoFl animals + BR1-NEMO, and 13 NemobeKO animals + BR1-NEMO), ***p = 0.0007, **p = 0.0038 (NemoKO:eGFP vs. NemoFl:NEMO ), **p = 0.0014 (NemoKO:NEMO vs. NemoKO:eGFP).",
    "ncbi_link": "Nemo: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter. All animals were at the age of 8-12 weeks.D IgG and albuminWestern blots of brain lysates. Less leakage in the BBB was detected in NemobeKO mice treated with AAV-BR1-NEMO than in NemobeKO mice injected with AAV-BR1-eGFP (the right panel indicates the quantified gel intensity under the various treatment conditions (n= 5 animals per group). NemoFl mice served as controls, ****p < 0.0001.",
    "ncbi_link": "Nemo: 16151
NEMO: 16151"
  },
  {
    "caption": "BR1-mediated expression of NEMO or eGFP was driven by the CAG promoter. All animals were at the age of 8-12 weeks.E Quantitative immunoglobulin staining of coronal brain sections of NemoFl and NemobeKO mice. Ig extravasation was significantly reduced in AAV-BR1-NEMO-treated mice (n= 9 NemoFl animals + BR1-eGFP, 10 NemobeKO animals + BR1-eGFP, 9 NemoFl animals + BR1-NEMO, and 13 NemobeKO animals + BR1-NEMO), ****p < 0.0001.",
    "ncbi_link": "NEMO: 16151
Nemo: 16151"
  },
  {
    "caption": "A In vitro differentiation to mature ookinete of wildtype (WT), Δisp1, Δisp3, and Δisp1/3 parasites. Values are means ± SD (n=4 biological replicates); two-tailed t test, *, P<0.05, **, P<0.01, ***, P<0.001, ns: not significant.",
    "ncbi_link": "isp3: 
isp1: 3807246"
  },
  {
    "caption": "G Western blot of ISP1 and ISP3 in zygote of the Δisp1/3 parasites episomally complemented with 3V5-tagged isp1 or 6HA-tagged isp3 genes from either P. yoelii or P. falciparum. P28 as loading control. The DTS (isp1::3V5;isp3::6HA) is a doubly-tagged parasite",
    "ncbi_link": "isp1: 
isp3: 
3V5: 
6HA: 
isp1: 3807246"
  },
  {
    "caption": "IFA of ISP1 and ISP3 expression from zygote to ookinete of the isp1::6HA and isp3::6HA parasites, respectively. Scale bar = 5 μm.",
    "ncbi_link": "6HA: 
isp3: 
isp1: 3807246"
  },
  {
    "caption": "B Co-localization of ISP1 and ISP3 from zygote to ookinete in the doubly-tagged strain (DTS, isp1::3V5;isp3::6HA). Scale bar = 5 μm.",
    "ncbi_link": "3V5: 
6HA: 
isp3: 
isp1: 3807246"
  },
  {
    "caption": "C Western blot of ISP1 and ISP3 expression in zygotes of isp1::6HA and isp3::6HA parasites. The numbers are the relative intensities of band in blot. Right panel: the quantification of band intensity. Values are means ± SEM (n=4 biological replicates), two-tailed t test, ****, P<0.0001.",
    "ncbi_link": "6HA: 
isp3: 
isp1: 3807246"
  },
  {
    "caption": "D Western blot of ISP1 and ISP3 expression in zygotes of DTS, DTS/Δisp1, and DTS/Δisp3 parasites. The numbers are the relative intensities of band in blot. Three replicates performed.",
    "ncbi_link": "isp3: 
isp1: 3807246"
  },
  {
    "caption": "E RT-qPCR analysis of isp1 and isp3 transcripts in zygotes of the WT, Δisp1, Δisp3, and Δisp1/3 parasites. The expression is normalized to the 18s rRNA. Values are means ± SEM (n=4 biological replicates).",
    "ncbi_link": "isp3: 
isp1: 3807246"
  },
  {
    "caption": "F IFA analysis of ISP1 and ISP3 expression dynamic of DTS/Δisp1 and DTS/Δisp3 parasites. Scale bar = 5 μm.",
    "ncbi_link": "isp3: 
isp1: 3807246"
  },
  {
    "caption": "E Substitutions of N-terminal cysteine or glycine residues to alanine (G2A or C7A/C8A) ablates palmitoylation of ISP1. ISP1 was fused with BFP::3V5 and episomally expressed in zygotes. Right panel shows quantification of palmitoylated protein band from two independent repeats, values are means ± SD.",
    "ncbi_link": "3V5: 
BFP: 
ISP1: 3807246"
  },
  {
    "caption": "H Expression and palmitoylation of ISP1 in ∆isp1/3 parasites complemented with the 3V5 tagged WT ISP1 or C7AC8A mutant.",
    "ncbi_link": "3V5: 
isp1: 3807246
ISP1: 3807246"
  },
  {
    "caption": "A Two-colored IFA of ISP1/DHHC2 and ISP3/DHHC2 at zygotes of the triple tagged strain isp1::3V5/isp3::6HA/dhhc2::4Myc (TTS). Right graph shows overlay of fluorescence peaks along cell periphery. Scale bar = 5 μm.",
    "ncbi_link": "3V5: 
4Myc: 
6HA: 
isp3: 
dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "C Knockdown of dhhc2 expression. Upper panel shows the promoter swap strategy applied in TTS strain, generating the dhhc2kd mutant with endogenous dhhc2 promoter replaced with clag promoter. Western blot confirming decreased expression of DHHC2 in dhhc2kd zygotes. Three replicates performed.",
    "ncbi_link": "dhhc2: 3807097
clag: 3830110"
  },
  {
    "caption": "D Two-colored IFA of DHHC2 and P28 proteins in the TTS and dhhc2kd zygotes. Scale bar = 5 μm. Bottom panel, quantifications of DHHC2 fluorescence. Values are means ± SD (n: the number of cells analyzed). Mann-Whitney test, ****, P<0.0001.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": "E Western blot of DHHC2, ISP1 and ISP3 in the TTS and dhhc2kd zygotes. Two replicates performed.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": "F Palmitoylation of ISP1 and ISP3 in the TTS and dhhc2kd zygotes using Acyl-RAC method. NH: NH2OH. Right panel indicates quantification of protein band intensity from three replicates, values are means ± SD.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": "G IFA of ISP1 and ISP3 in zygotes of TTS and dhhc2kd. Scale bar = 5 μm.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": " H Giemsa staining of zygote/ookinete from in vitro cultured TTS and dhhc2kd parasites. Scale bar = 5 μm.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": "J IFA of DHHC2 expression in the dhhc2::6HA and dhhc2::6HA;∆isp1/3 zygotes. Scale bar = 5 μm.",
    "ncbi_link": "6HA: 
dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "K Western blot of DHHC2 in zygotes of dhhc2::6HA and dhhc2::6HA;∆isp1/3.",
    "ncbi_link": "6HA: 
dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "L IFA of DHHC2 and ISP1 in zygotes of dhhc2kd parasites complemented with 4Myc tagged WT PyDHHC2 of P. yoelii, PfDHHC2 of P. falciparum, or PyDHHC2 with PAT catalytic deficient mutation C128A. Scale bar = 5 μm.",
    "ncbi_link": "4Myc: 
DHHC2: 
dhhc2: 3807097
DHHC2: 3807097"
  },
  {
    "caption": "M Western blot of DHHC2 in the complemented dhhc2kd parasites as indicated.",
    "ncbi_link": "dhhc2: 3807097"
  },
  {
    "caption": "D Acyl-RAC method detecting palmitoylation of endogenous DHHC2 in the dhhc2::6HA zygotes.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "G IFA of DHHC2 at the dhhc2::6HA zygotes treated with 100 μΜ 2-BP. Scale bar = 5 μm.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "H In vitro ookinete differentiation of the dhhc2kd parasites complemented with either WT DHHC2 or C4A mutant. Values are means ± SD from three independent tests.",
    "ncbi_link": "dhhc2: 3807097
DHHC2: 3807097"
  },
  {
    "caption": "J Palmitoylation of HA-tagged and human codon optimized DHHC2 ectopically expressed in human HEK293T cells. Both C4A and C128A mutations ablate DHHC2 palmitoylation.",
    "ncbi_link": "DHHC2: 3807097"
  },
  {
    "caption": "K DHHC2_C128A-HA mutant protein could be palmitoylated by the co-transfected DHHC2WT-Myc, but not DHHC2_C128A-Myc in HEK293T cells. Representative of two independent repeats.",
    "ncbi_link": "Myc: 
DHHC2: 3807097"
  },
  {
    "caption": "M C-terminus 75 residues peptide (Cter75) of DHHC2 could be palmitoylated as an independent substrate by co-transfected DHHC2WT-HA in HEK293T cells. Cter75 is fused with a BFP::Myc for easy detection via western blot. Cter75* peptide contains C4A mutation.",
    "ncbi_link": "HA: 
DHHC2: 3807097"
  },
  {
    "caption": "B Endogenous DHHC2 is palmitoylated in the dhhc2::6HA gametocytes.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "C Episomally expressed DHHC2 driven by promoter of ccp2 gene is palmitoylated in female gametocytes, female gametes, and zygotes of WT parasites. Left panel shows the expression of HA-tagged DHHC2 in female gametocyte by co-staining with antibodies of HA and α-Tubulin II (male gametocyte specific). Scale bar = 5 μm.",
    "ncbi_link": "ccp2: 3790830"
  },
  {
    "caption": "D IFA of DHHC2 and P28 in female gametocytes, female gametes, and zygotes of the dhhc2::6HA parasite. Gametocytes were stimulated with XA and 22°C in vitro. P28 is expressed specifically in female gametes and zygotes. Scale bar = 5 μm.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "F No polarization of DHHC2 in the dhhc2::6HA gametocytes with only either XA or 22°C stimulation. Three replicates performed, values are means ± SD.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "G No change in DHHC2 expression in zygotes of the dhhc2::6HA parasite-derived mutants with individual gene disruption of cdpk4, hap2, and dozi.",
    "ncbi_link": "6HA: 
dhhc2: 3807097
cdpk4: 3830518
hap2: 3790421
dozi: 3807001"
  },
  {
    "caption": "H Quantification of parasite with DHHC2 polarization in P28 positive cells. Parasites are indicated in (G) or from a genetic cross (dhhc2::6HA/cdpk4 and WT). x/y: the number of cells with DHHC2 polarization and the number of cells analyzed. Values are means ± SD from three tests, two-tailed t test, ***, P<0.001, ****, P<0.0001, ns, not significant.",
    "ncbi_link": "6HA: 
dhhc2: 3807097
cdpk4: 3830518"
  },
  {
    "caption": "I Expression and localization of DHHC2 and GAP45 during female gamete to ookinete development of dhhc2::6HA parasite. GAP45 is an IMC marker and is only detected in zygote after fertilization, but not gametes. Scale bar = 5 μm.",
    "ncbi_link": "6HA: 
dhhc2: 3807097"
  },
  {
    "caption": "A Transmission electron microscopy (TEM) cross sections of WT, dhhc2kd and ∆isp1/3 parasites showing the arrangement of SPM underneath IMC. Approximately 60 recognizable hollow microtubules (green) are associated with IMC (red), distributing evenly around circumference with an interval of 100-120 nm in WT ookinetes. Microtubules lost association with IMC in the ookinetes of dhhc2kd and ∆isp1/3 parasites. Left: one representative cell in each parasite is shown; Right: two areas are magnified to show the details. Lower panel is the quantification of distance between adjacent microtubules associated with IMC. Values are mean ± SD for n=204 (WT), 189 (dhhc2kd), and 211 (∆isp1/3) measurements in 20 cells each group from two independent experiments; Kolmogorov-Smirnov test, ****, P<0.0001.",
    "ncbi_link": "dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "B Apical polar ring and the emanating SPM in WT, dhhc2kd and ∆isp1/3 parasites examined by negative staining and TEM. A dome-like SPM structure radiating from the apical polar ring was observed in early (3 hours) or mature (12 hours) WT ookinetes, but impaired in mutant parasites. n is the number of cells analyzed from three independent experiments. More images in the Appendix Figure S5. Scale bar = 1μm.",
    "ncbi_link": "dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "C SiR-tubulin staining show the SPM structures of WT, dhhc2kd and ∆isp1/3 parasites. Arrowheads point to cell apical. Scale bar = 5 μm.",
    "ncbi_link": "dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "F Solubility assay detecting membrane association of α- and β-Tubulins in WT, dhhc2kd, and ∆isp1/3 parasites. GAPDH is a cytosol soluble protein, P28 is a plasma membrane integral protein.",
    "ncbi_link": "dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "H Linear correlation of membrane association index of α-Tubulin and β-Tubulin with the conversion rate to mature ookinete among WT, dhhc2kd and ∆isp1/3 parasites. Horizontal and vertical values are means ± SD.",
    "ncbi_link": "dhhc2: 3807097
isp1: 3807246"
  },
  {
    "caption": "a, Detection of wild-type (+) and Ambra1 gene-trap transcripts (gt) from total E14.5 embryos analysed by northern blotting. Size marker, 28S ribosomal RNA.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "c-f, Expression of Ambra1 in the mouse embryonic nervous system. β-gal-staining on whole-mount Ambra1+/gt mouseembryos at E8.5 (c), E11.5 (d) and on a cross-section of E11.5spinal cord (e) is shown. Fb, forebrain; Hb, hindbrain; Mb, midbrain. f, Matching expression of the endogenous gene was revealed by whole-mount Ambra1 mRNA in situ hybridization analysis in E11.5 wild-type embryos.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "g-l, Electron scanning microscopy analysis of E11.5 (g) and E12.5 (h) Ambra1gt/gt embryos. Note the failure of the neural tube closure, the extensive midbrain/hindbrain exencephaly (Ex) with a closed telencephalon (T), and the lumbosacral spina bifida (Sb). i, j, E14.5 wild-type (i) and Ambra1gt/gt (j) embryos are characterized by prominent exencephaly. k, l, Histological analysis of E12.5 wild-type (k) and Ambra1gt/gt (l) embryos on cross-section. Note the absence of a normal ventricular system, the extensive overgrowth of the proliferative neuroepithelium in the diencephalon (Di) and spinal cord (Sc), and the enlarged fifth ganglia (VG) in the Ambra1gt/gt embryo.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "m-p, TUNEL (TdT-mediated dUTP nick end labelling) staining of E10.5brain (m, n) and E9.5spinal cord (o, p) in wild-type (m, o) and Ambra1gt/gt (n, p) embryo sections. q-t, Analysis of cell proliferation in wild-type (q, s) and Ambra1gt/gt (r, t) embryos on transverse sections of E8.5cephalic neural folds in prospective hindbrain region (mitoses, arrows in q, r) and on sagittal sections of E10.5forebrain (BrdU uptake, s, t).",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "a, AMBRA1-BECN1 interaction by yeast two-hybrid assay. Yeast cells were co-transfected with the indicated plasmids and plated in medium with (+) or without (-) histidine (H) and adenine (A). AD, activation domain; DBD, DNA-binding domain; G4, Gal4; LAM, lamin.",
    "ncbi_link": "Gal4: 
lamin: "
  },
  {
    "caption": "e, BECN1 and AMBRA1 co-localize in mammalian cells. 2FTGH cells co-expressing BECN1 and Myc-tagged AMBRA1 were stained for Myc (green) and BECN1 (red). Scale bars, 8 µm.",
    "ncbi_link": "AMBRA1: "
  },
  {
    "caption": "a, AMBRA1 downregulation in 2FTGH cells using specific short interfering RNA (siRNA) oligoribonucleotides (1 and 2). AMBRA1 mRNA and protein levels were analysed by quantitative polymerase chain reaction (PCR, left) and western blotting (right), respectively. An unrelated oligoribonucleotide was used as the control. Tubulin was used as the protein-loading control. RL, relative levels. The arrowhead indicates the AMBRA1-specific band.",
    "ncbi_link": "AMBRA1: "
  },
  {
    "caption": "b, Rapamycin-induced autophagy requires AMBRA1. After AMBRA1 downregulation, 2FTGH cells were treated with rapamycin; after 48 h, the occurrence of autophagy was analysed by appearance of GFP-LC3 punctate staining or by LC3-I to LC3-II conversion (western blot in inset). Representative results are accompanied by a graph reporting data from three experiments. Scale bar, 20 µm.",
    "ncbi_link": "AMBRA1: "
  },
  {
    "caption": "c, Nutrient-starvation-induced autophagy requires AMBRA1. After AMBRA1 downregulation, 2FTGH cells were starved for 4 h and analysed for appearance of GFP-LC3 punctate staining.",
    "ncbi_link": "AMBRA1: "
  },
  {
    "caption": "d, AMBRA1 overexpression increases basal and rapamycin-induced autophagy. 2FTGH cells were transduced with full-length AMBRA1 (FL), AMBRA1 fragments (F1-3), BECN1 and β-gal (negative control) encoding retroviruses. They were then stimulated with rapamycin or left untreated, and analysed by appearance of GFP-LC3 punctate staining.",
    "ncbi_link": "AMBRA1: 
BECN1: 8678"
  },
  {
    "caption": "e, BECN1-induced autophagy requires AMBRA1. After AMBRA1 downregulation, GFP-LC3-expressing 2FTGH cells were transduced with a BECN1-encoding retrovirus. Occurrence of autophagy was analysed 48 h later by appearance of GFP-LC3 punctate staining.",
    "ncbi_link": "AMBRA1: 
BECN1: 8678"
  },
  {
    "caption": "f, AMBRA1 downregulation reduces the amount of Vps34 associated to BECN1 during autophagy. Forty-eight hours after AMBRA1 downregulation with oligo 2, 2FTGH cells were either starved or cultured in standard medium for an additional 4 h. Protein extracts were immunoprecipitated (IP) using an anti-BECN1 antibody. Purified complexes and corresponding total extracts were analysed by western blotting with anti-Vps34 (left panels) and anti-BECN1 (right panels) antibodies. The graph indicates the signal intensity of BECN1-associated Vps34 as determined by densitometry.",
    "ncbi_link": "AMBRA1: "
  },
  {
    "caption": "c, Rapamycin-induced autophagy is impaired in Ambra1gt/gt murine embryonic fibroblasts (MEFs). Cells dissected from embryos with different genotypes (A-D) were treated with rapamycin, and the occurrence of autophagy was analysed 48 h later by the appearance of GFP-LC3 punctate staining. Representative results are shown in the upper panels, whereas the lower panel shows the data from three experiments. Scale bar, 20 µm.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "A-C Calcium flux measured by FACScan for splenic B cells isolated from Lyn-deficient B1-8 transgenic mice after stimulation with (A) NIP15-BSA (30 pM) or 1NIP-pep (80 nM); (B) Ac146 antibody (12.5 nM) or Ac146Fab (25 nM); (C) Ac38 antibody (12.5 nM) or Ac38Fab (25 nM). Arrows indicate the addition of the stimuli to the cells.",
    "ncbi_link": "Lyn: 17096"
  },
  {
    "caption": " (B) Hematoxylin and (Periodic acid-Shiff) PAS staining of WT (left) and Hnf4g KO (right) intestine. Nuclei are visualized using Hematoxylin and goblet cells stain positive for PAS ",
    "ncbi_link": "Hnf4g: 30942"
  },
  {
    "caption": " (C) Alcian Blue and Nuclear Fast Red staining of WT (left) and Hnf4g KO (right)  small intestinal  organoids. Cells are visualized using Nuclear Fast Red. Intra- and extracellular mucus that is produced in goblet cells stain positive for Alcian Blue ",
    "ncbi_link": "Hnf4g: 30942"
  },
  {
    "caption": " (D) Strand specific RNA-seq data, Hnf4g ChIP-seq in EN, and promoter specific histone modification H3K4me3 over the Hnf4a locus is shown. Data from different organoid cultures are color coded.  RNA-seq  reads mapping to the positive strand (sense strand) are plotted in the top window of every sample, while RNA-seq reads that map to the negative strand are mirrored and shown in the bottom window of every sample. The two isoforms of Hnf4a that are expressed are shown in the bottom, together with the antisense transcript Hnf4aos. The \"phyloP30way\" track from the UCSC genome browser is plotted at the bottom to show sequence conservation ",
    "ncbi_link": "Hnf4a: 15378
Hnf4aos: 68314"
  },
  {
    "caption": " (E) Quantification of the amount of  goblet cells  per villus for WT and Hnf4g KO intestine. Dots represent the amount of goblet cells  counted per villus. (n = 7 to 25 villi from 11 WT mice and 3 to 17 villi from 14 Hnf4g KO mice). P value is from two-tailed Mann-Whitney U test ",
    "ncbi_link": "Hnf4g: 30942"
  },
  {
    "caption": " A Scatter plot of RNA-seq expression analysis. 508 genes were upregulated and 391 genes were downregulated. Human MSCs were transfected with USP34 or control siRNAs and cultured in osteogenic medium for 2 days. Two biological replicates per group ",
    "ncbi_link": "USP34: 9736"
  },
  {
    "caption": "E Immunoblot analysis of BMP2-induce Sp7 expression. Prx1-Cre;Usp34f/f and Usp34f/f control MSCs were starved overnight and then stimulated with 100 ng/ml BMP2 for 24 hours",
    "ncbi_link": "Prx1: 
Usp34: 17847"
  },
  {
    "caption": "F Quantitative RT-PCR analysis of BMP2-induce Sp7 transcription. Cells were depleted from serum overnight before BMP2 stimulation. Results are shown as mean ± SEM; n=3; *: p<0.05 and **: p<0.01 by t test",
    "ncbi_link": "Sp7: 170574"
  },
  {
    "caption": " B Immunoblot analysis showing decreased FLAG-Smad1 after USP34 knockdown ",
    "ncbi_link": "USP34: 9736"
  },
  {
    "caption": " C Immunoblot of Smad1-linked polyUb. 293T cells were co-transfected with FLAG-Smad1 overexpression plasmid and USP34 siRNA, and treated with 10 µM MG132 for 4 hours before collection ",
    "ncbi_link": "Smad1: 4086
USP34: 9736"
  },
  {
    "caption": " D Immunoblot analysis of the degradation of FLAG-Smad1 protein. 293T cells were co-transfected with FLAG-Smad1 overexpression plasmid and USP34 siRNA, and treated with 50 µg/ml cycloheximide (CHX) before collection at designated time points. Right: relative quantification of FLAG-Smad1 protein levels at different time points",
    "ncbi_link": "Smad1: 4086
USP34: 9736"
  },
  {
    "caption": "G Immunoblot of RUNX2-linked polyUb. Differentiated mouse MSCs were treated with 10 µM MG132 for 4 hours before collection. Prx1-Cre(+) indicates MSCs isolated from Prx1-Cre;Usp34f/f mice, and Prx1-Cre(-) indicates those from Usp34f/f control mice",
    "ncbi_link": "Prx1: 
Usp34: 17847"
  },
  {
    "caption": "H Immunoblot analysis of the degradation of endogenous RUNX2 protein in MSCs. Prx1-Cre;Usp34f/f and Usp34f/f control MSCs were stimulated with BMP2, treated with 50 µg/ml CHX, and collected at designated time points. Right: relative quantification of RUNX2 protein levels at different time points",
    "ncbi_link": "Prx1: 
Usp34: 17847"
  },
  {
    "caption": "I Representative images of ALP and ARS staining. Usp34f/f and Prx1-Cre;Usp34f/f MSCs were transduced with GFP, Smad1, Runx2 or Smad1+Runx2 adenoviruses, and then cultured in osteogenic medium for 5 and 10 days, respectively",
    "ncbi_link": "Prx1: 
Runx2: 12393
Smad1: 17125
Usp34: 17847"
  },
  {
    "caption": "B Immunoblot analysis of BMP2-induce Sp7 expression. Prx1-Cre;Usp34f/f MSCs were treated with Smurf1 or control siRNAs, starved overnight and then stimulated with 100 ng/ml BMP2 for 24 hours",
    "ncbi_link": "Prx1: 
Smurf1: 75788
Usp34: 17847"
  },
  {
    "caption": "C Quantitative RT-PCR analysis of BMP2-induce Sp7 transcription. Prx1-Cre;Usp34f/f MSCs were treated with Smurf1 or control siRNAs, and depleted from serum overnight before BMP2 stimulation. Results are shown as mean ± SEM; n=3; *: p<0.05 and **: p<0.01 by ANOVA with Tukey's post hoc test",
    "ncbi_link": "Prx1: 
Smurf1: 75788
Sp7: 170574
Usp34: 17847"
  },
  {
    "caption": " F Representative images of ALP and ARS staining. Mouse MSCs were treated with Smurf1 or control siRNAs, and cultured in osteogenic medium for 5 and 10 days, respectively",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "I, J Quantitative RT-PC analyses of the expression of osteogenic markers. Cells were treated with Smurf1 or control siRNAs, and cultured in osteogenic medium for 5 days. Results are shown as mean ± SEM; n=3; *: p<0.05, **: p<0.01 and ***: p<0.001 by ANOVA with Tukey's post hoc test",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "western blot analyses of the expression of osteogenic markers. Cells were treated with Smurf1 or control siRNAs, and cultured in osteogenic medium for 5 days. Results are shown as mean ± SEM; n=3; *: p<0.05, **: p<0.01 and ***: p<0.001 by ANOVA with Tukey's post hoc test",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "(F) SCD1 overexpression affects RNF145/ADIPOR2. HEK-293T cells containing an empty control vector or expressing SCD1-HA were cultured in FCS-free DMEM for 24h and whole-cell lysates analysed. * non-specific bands.",
    "ncbi_link": "HA: 
SCD1: 6319"
  },
  {
    "caption": "(A) Endogenous ADIPOR2 is stabilised in RNF145 knockout cells. Representative 35S pulse-chase analysis in HeLa WT, RNF145 knockout (∆RNF145) or ADIPOR2 knockout (∆AR2) cells. Quantification of 35S-labelled ADIPOR2 normalised to t = 0 h is shown below.",
    "ncbi_link": "ADIPOR2: 79602
AR2: 79602
RNF145: 153830"
  },
  {
    "caption": "(B) ADIPOR2 regulation requires the E3 ligase activity of RNF145. HEK-293T RNF145 knockout cells (∆RNF145) were stably complemented with WT RNF145 (RNF145-V5) or an inactive RNF145C552A,H554A RING domain mutant (mRNF145-V5). * non-specific bands.",
    "ncbi_link": "V5: 
RNF145: 153830"
  },
  {
    "caption": "(C) RNF145 binds ADIPOR2. RNF145 was immunoprecipitated from HeLa RNF145 knockout cells complemented with WT RNF145 (RNF145-V5) or an inactive RNF145C552A,H554A RING domain mutant (mRNF145-V5). Cells were treated with VCP inhibitor (NMS-873, 10 µM, 90 min) prior to immunoprecipitation with an anti-V5 antibody.",
    "ncbi_link": "V5: 
RNF145: 153830"
  },
  {
    "caption": "(D) The E2 ubiquitin-conjugating enzyme UBE2G2 is involved in RNF145-mediated ADIPOR2 degradation. Immunoblot analysis of HEK-293T cells depleted of RNF145 (gRNF145), UBE2G2 (gUBE2G2) or B2M (control; gCTR).",
    "ncbi_link": "B2M: 567
RNF145: 153830
UBE2G2: 7327"
  },
  {
    "caption": "(E) ADIPOR2 degradation depends on UBXD8. HEK-293T cells were depleted of B2M (gCTR) or UBXD8 (gUBXD8) and analysed by immunoblotting.",
    "ncbi_link": "B2M: 567
UBXD8: 23197"
  },
  {
    "caption": "(B) UBXD8 participates in PA-modulated RNF145 degradation. CRISPR/Cas9-mediated depletion of UBXD8 (gUBXD8) or B2M (gB2M, control) in HEK-293T cells, followed by exposure to PA (400 µM, 6h) or BSA (6h, vehicle control).",
    "ncbi_link": "CRISPR: 
B2M: 567
Cas9: 69900935
UBXD8: 23197"
  },
  {
    "caption": "(C) PA and OA treatment alter RNF145 ubiquitination. Immunoprecipitation of RNF145 from cells treated with BSA (control), PA or OA (each 200 µM, 3h). During FA treatments, VCP inhibitor (NMS-873, 10 µM) was present to stabilise ubiquitinated proteins. RNF145 ubiquitination (ubi) was detected using an anti-ubiquitin antibody (VU-1).",
    "ncbi_link": "RNF145: 153830"
  },
  {
    "caption": "(E) Lysine-less RNF145 is stabilised under PA treatment. RNF145 knockout HEK-293T cells (∆RNF145) were complemented with RNF145-V5 or a lysine-less variant of RNF145 (RNF145-V5 K > R) and treated BSA or PA (400 µM, 6h). Dotted lines demarcate the different cell lines.",
    "ncbi_link": "V5: 
RNF145: 153830"
  },
  {
    "caption": "(F) Adjustment of RNF145 levels to PA requires its ubiquitin ligase activity. Immunoblot of whole-cell lysates from RNF145 knockout HEK-293T (∆RNF145) cells stably complemented with RNF145-V5 or RNF145C552A, H554A-V5 (mRNF145-V5) and treated with BSA or PA (400 µM, 6h). LE, long exposure.",
    "ncbi_link": "V5: 
RNF145: 153830"
  },
  {
    "caption": "(A) ADIPOR2 regulation by FAs is completely dependent on RNF145. WT or RNF145 knockout HEK-293T cells (∆RNF145) were treated with BSA, PA or OA (400 µM, 6h) and analysed by immunoblotting. Non-specific bands are indicated (*).",
    "ncbi_link": "RNF145: 153830"
  },
  {
    "caption": "(B) RNF145 - ADIPOR2 interaction is FA-modulated. Immunoprecipitation of endogenous RNF145 HEK-293T cells depleted of UBE2G2 (gUBE2G2) and/or RNF145 (gRNF145) and treated with 400 µM of the indicated PA, OA or BSA (control) for 3h. LE, long exposure. * non-specific bands.",
    "ncbi_link": "RNF145: 153830
UBE2G2: 7327"
  },
  {
    "caption": "(C) Immunoprecipitation (IP) of endogenous ADIPOR2 from WT or ∆RNF145 cells (see (C)) treated with MG132 (5 µg/ml, 6h) ± OA (200 µM, 6h). Ubiquitinated ADIPOR2 was detected using a specific anti-ubiquitin antibody (clone VU-1). Note that ADIPOR2 levels in RNF145 knockout HEK-293T cells are increased.",
    "ncbi_link": "RNF145: 153830"
  },
  {
    "caption": "(D) ADIPOR2 knockout HEK-293T cells were stably complemented with ADIPOR2-HA, an ADIPOR2 mutant in which all lysines were mutated to arginines (K-less ADIPOR2-HA), or an empty vector control and exposed to OA (200 µM, 6h) or BSA (control). ADIPOR2 variants were visualised by immunoblotting using a specific anti-HA antibody. LE, long exposure.",
    "ncbi_link": "HA: 
ADIPOR2: 79602"
  },
  {
    "caption": "(A) Loss of ADIPOR2 sensitises cells to PA-induced cytotoxicity. HEK-293T cells were depleted of RNF145 (purple), ADIPOR2 (blue), B2M (CTR; grey), or both ADIPOR2 and RNF145 (blue + purple), exposed to PA (200 µM, 96h) and stained with crystal violet. Quantification of crystal-violet stained cells is shown alongside a representative micrograph (below). The response of each cell line to PA was normalised to its BSA-treated condition (dotted line). Statistically significant differences to cells containing gCTR cells are indicated (robust one-way ANOVA with Benjamini-Hochberg multiple testing correction). Mean ± SD are shown. Boxplots represent the median, first and third quantiles. Upper and lower whiskers extend to values up to 1.5-fold interquartile range. N = 3 biological replicates, ** q ≤ 0.01. Double knockdowns were generated by sequential constitutive CRISPR/Cas9-mediated depletion of RNF145 or ADIPOR2. Knockdown efficiencies are shown in Appendix Fig S1A.",
    "ncbi_link": "CRISPR: 
ADIPOR2: 79602
B2M: 567
Cas9: 69900935
RNF145: 153830"
  },
  {
    "caption": "(C) HEK-293T cells depleted of B2M (gCTR) or ADIPOR2 (gADIPOR2) were complemented with empty vector (blue), full-length ADIPOR2-HA (green), or a catalytically inactive variant of ADIPOR2-HA (dead ADIPOR2; red) and treated with PA (200 µM, 96h) or BSA (vehicle control, 96h). Measurements from PA-treated cells were normalised to their BSA-treated condition (dotted line). Cell growth was quantified, and representative crystal violet staining is shown. Boxplots represent the median, first and third quantiles. Upper and lower whiskers extend to values up to 1.5-fold interquartile range. ** q ≤ 0.01 (robust one-way ANOVA with Benjamini-Hochberg multiple testing correction).",
    "ncbi_link": "HA: 
ADIPOR2: 79602
B2M: 567"
  },
  {
    "caption": "(E) Reduced glutathione (GSH) partially blocks mitochondrial fission. Neurons were transfected with Mito pretreated for 2 h with 2 mM GSH monoethyl ester, washed once and then exposed to 35 μM SNOC. Mitochondrial fission was scored after 1 h. Data are means±s.e.m. of quintuplicate samples from one representative experiment of a total of three (†††significance at P0.001 or n.s., †not significant compared to control; *significance at P0.05).",
    "ncbi_link": "Mito: "
  },
  {
    "caption": "(B) Percentage of mitochondrial fission and cell death at 18 h († and ††† significance at P0.05 and 0.001 as compared to control pcDNA3 transfection; *,** and *** significance at P0.05 , 0.01 and 0.001, respectively, compared to SNOC treated, pcDNA3 transfected neurons; n=3 independent experiments). Dying neurons were recognized by their shrunken and condensed nuclei after Hoechst 33342 staining.",
    "ncbi_link": "pcDNA3: "
  },
  {
    "caption": "(C) Enforced Drp1 or Fis1 expression (60 h) evokes fission and neuronal cell death (*,** and *** significance at P0.05, 0.01 and 0.001, respectively, compared to pcDNA3 transfected neurons; n=3 independent experiments).",
    "ncbi_link": "pcDNA3: 
Drp1: 114114
Fis1: 288584"
  },
  {
    "caption": "(E) Mfn1 or Drp1K38A inhibits 100 nM rotenone‐induced mitochondrial fission (4 h) and cell death (48 h). Data indicate means±s.e.m. of triplicate measurements (†† and ††† significance at P0.01 and 0.001 as compared to untreated control; ***significance at P0.001 as compared to rotenone treatment with pcDNA3 transfection; n=3).",
    "ncbi_link": "pcDNA3: 
Drp1: 114114
Mfn1: 192647"
  },
  {
    "caption": "(F) Mitochondrial fission by Aβ35-25 or Aβ25-35 exposure. The fraction of neurons exhibiting fragmented mitochondria is shown as the mean±s.e.m. (††significance at P0.01 compared to pcDNA3 transfected, Aβ35−25 treated control; * and ** significance at P0.05 and 0.001, respectively, compared to pcDNA3 transfected, Aβ25-35 treated neurons; n=3).",
    "ncbi_link": "pcDNA3: "
  },
  {
    "caption": "(B) qPCR  analysis of Nrf1, Gabpa  and Ppargc1a  mRNA in mouse PMs  infected with VSV  or HSV-1 or treated with poly(I:C) or ISD  for the indicated time points (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "Gabpa: 14390
Nrf1: 18181
Ppargc1a: 19017"
  },
  {
    "caption": "(C) Immunoblot  analysis of NRF1  expression in mouse PMs  transfected with p65-specific siRNA (si-p65) or control siRNA (si-NC) for 48 h, followed by infection with VSV  or HSV-1 for 8 h. GAPDH  was used as a loading control. Ratios of target proteins versus loading control normalized to the untreated sample of each condition.",
    "ncbi_link": "p65: 20979"
  },
  {
    "caption": "(E) Immunoblot  analysis of mitochondrial proteins and autophagy marker LC3  in mouse PMs  transfected with NRF1-specific siRNA (si-NRF1) or control siRNA (si-NC) for 48 h, followed by infection with VSV  or HSV-1 for the indicated time points. ACTIN was used as a loading control. Ratios of target proteins versus loading control normalized to the untreated sample of each condition.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(F) Mitochondrial mass  determined by mtDNA/nuclear DNA (nDNA) ratio in mouse PMs  transfected with NRF1-specific siRNA (si-NRF1) or control siRNA (si-NC) for 48 h, followed by infection with VSV  or HSV-1  for the indicated time points (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "RNA-sequencing  (RNA-seq) analysis of  gene expression in wild-type and NRF1-KO mouse PMs  (n=3 biological replicates per group) infected with VSV  for 8 h. (C) Pheatmap analysis showing downregulated DEGs encoding  mitochondrial inner membrane  proteins. TPM, transcripts per kilobase of exon model per million mapped reads.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(D) Mitochondrial mass  determined by mtDNA/nuclear DNA (nDNA) ratio in wild-type and NRF1-KO mouse PMs  infected with VSV  or HSV-1  for the indicated  time points (n=3 biological replicates per group). Data information: Data are from three independent experiments (D) and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(F and G) The representative curves of oxygen consumption rate  (OCR) in wild-type and NRF1-KO mouse PMs  infected with VSV  (F) or HSV-1 (G) for 8 h (n=5 biological replicates per group). Oligomycin: 1 µM, FCCP: 4 µM, Rotenone: 1 µM. Quantification of basal and maximal OCR. Data information: Data are from at least three biological replicates and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(H and I) Electron micrographs  of mitochondria  in wild-type and NRF1-KO mouse PMs  infected with VSV or HSV-1 for 8 h. Scale bars, 500 nm (H). (I) Quantitative analysis of mitochondrial cristae (the ratio of cristae  number to mitochondrial  area) in (H) (20-30 mitochondria  per group, biological replicates). Data information: Data are from at least three biological replicates and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(A) Luciferase activity of IFN-β, NF-κB and ISRE  promoter reporter in HEK293T  cells transfected with empty vector or plasmids encoding incremental NRF1-Myc  for 24 h followed by infection with VSV  for 8 h (n=4 biological replicates per group).",
    "ncbi_link": "Myc: 
IFN-β: 3456
NRF1: 4899"
  },
  {
    "caption": "(B and C) Immunoblot  analysis of phosphorylated  and total TBK1, p65  and STAT1  in wild-type and NRF1-KO mouse PMs  infected with VSV  or HSV-1  (B) or stimulated with poly(I:C) or ISD  (C) for the indicated time points. GAPDH  was used as a loading control. Ratios of phosphorylated  proteins versus total proteins normalized to the 0-h or 4-h  time point of each wild-type sample.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(D) qPCR  analysis of Ifnb1, Il6, Tnfa  and Cxcl10  mRNA in wild-type and NRF1-KO mouse PMs  infected with VSV  or HSV-1  or stimulated with  poly(I:C)  or ISD  for the indicated time points (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ND, not detectable, *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "Cxcl10: 15945
Ifnb1: 15977
Il6: 16193
NRF1: 18181
Tnfa: 21926"
  },
  {
    "caption": "(E) ELISA  quantification of  IFN-β, IL6  and TNF-α secretion in wild-type and NRF1-KO mouse PMs  treated as in (D) (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ND, not detectable, *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(A) 8-week-old Nrf1F/F and Nrf1MyeKO mice  (n=3 for PBS  treatment and n=6 for virus treatment) were intravenously infected with VSV  (4×107 PFU/mouse) or HSV-1 (1×107 PFU/mouse). After 24 h, ELISA  quantification of IFN-β, IL6  and TNF-α in sera. Data information: Data are presented as mean ± s.e.m. Two-tailed, unpaired Student's t test were used to measure significance. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Nrf1: 18181"
  },
  {
    "caption": "(B) qPCR  analysis of Ifnb1, Il6  and Tnfa  mRNA in the lung  of Nrf1F/F and  Nrf1MyeKO mice  infected with VSV  as in A (n=6 per group). Data information: Data are presented as mean ± s.e.m. Two-tailed, unpaired Student's t test were used to measure significance. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Ifnb1: 15977
Il6: 16193
Nrf1: 18181
Tnfa: 21926"
  },
  {
    "caption": "(C) qPCR  analysis of VSV  mRNA and  plaque assay of VSV  titers in the lungs  of  Nrf1F/F and Nrf1MyeKO mice  infected with VSV  as in A (n=6 per group). Data information: Data are presented as mean ± s.e.m. Two-tailed, unpaired Student's t test were used to measure significance. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Nrf1: 18181"
  },
  {
    "caption": "(E) qPCR  analysis of Ifnb1, Il6  and Tnfa  mRNA in the brains  of Nrf1F/F and Nrf1MyeKO mice  infected with HSV-1 as in (A) (n=6 per group). (F) qPCR  analysis of HSV-1 UL30  mRNA and plaque assay  of HSV-1 titers in the brain  of Nrf1F/F and Nrf1MyeKO mice  infected with HSV-1 as in (A) (n=6 per group). Data information: Data are presented as mean ± s.e.m. Two-tailed, unpaired Student's t test were used to measure significance. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Ifnb1: 15977
Il6: 16193
Nrf1: 18181
Tnfa: 21926
UL30: 2703462"
  },
  {
    "caption": "(G) Survival  of Nrf1F/F and Nrf1MyeKO mice  (n=10 per group) at various times  after intraperitoneal  (i.p.) infection with HSV-1 (2×107 PFU per mouse). Data information: Data are presented as mean ± s.e.m. log-rank (Mantel-Cox) test (G) were used to measure significance. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Nrf1: 18181"
  },
  {
    "caption": "(A) mtROS levels measured by MitoSOX staining  and  flow cytometry in wild-type and NRF1-KO mouse PMs  infected with VSV  (left) or HSV-1  (right) for the indicated time points. MFI, mean fluorescence intensity (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(B) DNA was isolated from digitonin  extracts of wild-type and NRF1-KO mouse PMs  infected with VSV  (left) or HSV-1 (right) for the indicated  time points. Cytosolic  translocation of mtDNA  was quantified via qPCR  using the indicated primer sets. 18S rRNA served as a control (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "18S rRNA: 
NRF1: 18181"
  },
  {
    "caption": "(C and D) Wild-type and NRF1-KO mouse PMs  infected with VSV  (8 h) or HSV-1 (4 h) were imaged by confocal microscope after staining  with anti-DNA  (DNA) and anti-Prohibitin  (Mito) antibodies. Scale bars, 5 µm (C). (D) The number of cytosolic mtDNA  puncta per cell was quantitated by ImageJ (n=30 cells per group). Data information: Data are from three independent experiments or representative data (C) and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(E) ELISA  quantification of IFN-β (left) and IL6  (right) in wild-type and NRF1-KO mouse PMs  pretreated with or without EtBr  (450 ng/ml, 72 h), followed by infection with VSV  or HSV-1 for 8 h (n=3 biological replicates per group). (F) ELISA  quantification of IFN-β (left) and IL6  (right) in wild-type and NRF1-KO mouse PMs  pretreated with or without MitoQ  (100 nM, 2 h), followed by infection with VSV  or HSV-1 for 8 h (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(H) qPCR  analysis of Ifnb1  and Il6  mRNA in the lungs  of Nrf1F/F and Nrf1MyeKO mice  pretreated with MitoQ  as in (G) and 1 h later infected i.p. with VSV  (5×108 PFU/mouse) for 24 h (n=6 per group). (I) qPCR  analysis of Ifnb1  and Il6  mRNA in the brains  of Nrf1F/F and Nrf1MyeKO mice  pretreated with MitoQ  as in (G) and 1 h later infected i.p. with HSV-1 (1×107 PFU/mouse) for 24 h (n=6 per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01, ***p < 0.001, using a two-tailed, unpaired Student's t test.",
    "ncbi_link": "Ifnb1: 15977
Il6: 16193
Nrf1: 18181"
  },
  {
    "caption": "(G) Endogenous phospho-NRF1  S318 signal was detected in wild-type and NRF1  S318A mouse PMs  after the infection with different viruses for 8 h. The red arrows indicate phosphorylated  signals for NRF1.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(J) ELISA  quantification of  IFN-β and IL6  secretion in wild-type and NRF1  S318A mouse PMs  treated as in (I) (n=3 biological replicates per group). Data information: Data are from three independent experiments and presented as mean ± s.e.m. ns, not significant (p > 0.05), *p < 0.05, **p < 0.01. Two-tailed, unpaired Student's t test were used to measure significance.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "(L) Survival  of wild-type and NRF1  S318A mice  (n=10 per group) at various times  after intraperitoneal infection with HSV-1 (2×107 PFU per mouse). Data information: log-rank (Mantel-Cox) test (L) were used to measure significance.",
    "ncbi_link": "NRF1: 18181"
  },
  {
    "caption": "C. WT and mutant 7SK fragment 5 containing U250G were analyzed as in B.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "E. 7SK RNA, generated by either in vitro transcription (IVT) or purified from HeLa total RNA and then site-specifically labeled at the indicated positions by the procedure in D, was analyzed by 1D-TLC.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "F. Cyber Gold staining of 7SK obtained by either IVT or immunoprecipitation (IP) with the indicated antibodies.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "G. 2D-TLC analysis of 32p-labeled mononucleotides derived from IVT or CDK9-bound 7SK RNA, with the first panel depicting a schematic migration pattern of the indicated 5'-phosphorylated mononucleotides.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "H. 7SK RNA, obtained by either IVT or anti-CDK9 IP and then site-specifically labeled at the indicated positions by the procedure in D, was analyzed by 1D-TLC.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "C-F; H-K; and N-Q. The tagged WT or mutant 7SK RNA was co-transfected with the indicated Flag-tagged proteins into HeLa cells. Anti-Flag or immunoprecipitates (IP) were analyzed by immunoblotting for the indicated proteins and primer extension for the bound 7SK RNA.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "C-F; H-K; and N-Q. The tagged WT or mutant 7SK RNA was co-transfected with the indicated Flag--tagged proteins into HeLa cells. Anti-Flag immunoprecipitates (IP) were analyzed by immunoblotting for the indicated proteins and primer extension for the bound 7SK RNA.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "C-F; H-K; and N-Q. The tagged WT or mutant 7SK RNA was co-transfected with the indicated Flag-tagged proteins into HeLa cells. Anti-Flag immunoprecipitates (IP) were analyzed by immunoblotting for the indicated proteins and primer extension for the bound 7SK RNA.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "C-F; H-K; and N-Q. The tagged WT or mutant 7SK RNA was co-transfected with the indicated HA-tagged proteins into HeLa cells. Anti-HA immunoprecipitates (IP) were analyzed by immunoblotting for the indicated proteins and primer extension for the bound 7SK RNA.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "R. The indicated 7SK were in vitro transcribed in the presence of 32p-UTP and subjected to in vitro modification reactions. The nuclease P1-digested products were analyzed by 1D-TLC with pU and pΨ as controls.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "A. Anti-V5immunoprecipitates (IP) from HeLa cells expressing nothing (-) or V5-DKC1 were analyzed by immunoblotting for V5-DKC1 and qRT-PCR for the bound 7SK RNA. The error bars represent mean ± SD from three independent experiments.",
    "ncbi_link": "DKC1: 1736
7SK: 125050"
  },
  {
    "caption": "B. Anti-FlagIP from NE of HeLa or the HeLa-derived F1C2 cells expressing CDK9-F were analyzed by Western blotting (WB) for the indicated proteins and primer extension (PEx) for 7SK RNA.",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "C. WB analysis of DKC1 and CDK9 levels in two HeLa clones inducibly expressing shDKC1 upon doxycycline (DOX) treatment for 5 days.",
    "ncbi_link": "DKC1: 1736"
  },
  {
    "caption": "D. The 7SK RNA levels in these two clones were detected by qRT-PCR before and after the DOX treatment and normalized to the GAPDH mRNA levels. The error bars represent mean ± SD from three independent experiments.",
    "ncbi_link": "GAPDH: 
7SK: 125050"
  },
  {
    "caption": "E. 1D-TLC analysis of Ψ250 in 7SK RNA from inducible DKC1 KD clone 1 before and after the DOX treatment.",
    "ncbi_link": "DKC1: 1736
7SK: 125050"
  },
  {
    "caption": "F. NE and anti-CDK9IP from NE of inducible DKC1 KD clone 1, which was untreated or treated with DOX, were analyzed by WB for the indicated proteins and PEx for 7SK RNA.",
    "ncbi_link": "DKC1: 1736
7SK: 125050"
  },
  {
    "caption": "A. Luciferase activities were measured in HeLa cells transfected with the indicated reporter constructs, an empty vector (-) or the Tat cDNA, and either siDKC1 or a non-target siRNA (siNT). For each reporter, the activity in cells expressing siNT was set to 1.",
    "ncbi_link": "Luciferase: 
DKC1: 1736
Tat: 155871"
  },
  {
    "caption": "B, C, and E. The mRNA levels of luciferase (B) or Tat (C & E) in cells expressing the indicated siRNAs were determined by qRT-PCR and normalized to the GAPDH mRNA and plotted.",
    "ncbi_link": "GAPDH: 
luciferase: 
Tat: 155871"
  },
  {
    "caption": "D. NH1 cells containing the integrated HIV-1 LTR-luciferase reporter and expressing Tat were transfected with siDKC1 or siNT. ChIP-qPCR analysis was performed to determine the levels of the indicated factors bound to the HIV-1 promoter. The signals were normalized to those of input and plotted.",
    "ncbi_link": "HIV-1 LTR: 
luciferase: 
DKC1: 1736"
  },
  {
    "caption": "B, C, and E. The mRNA levels of Tat (C & E) in cells expressing the indicated siRNAs were determined by qRT-PCR and normalized to the GAPDH mRNA and plotted.",
    "ncbi_link": "GAPDH: 
Tat: 155871"
  },
  {
    "caption": "F. Western analysis of DKC1 and CDK9 levels in a Jurkat 2D10-derived clone inducibly expressing shDKC1 upon exposure to DOX.",
    "ncbi_link": "DKC1: 1736"
  },
  {
    "caption": "G and H. The inducible DKC1 KD clone, treated or untreated with DOX for 4 days, was incubated with the indicated concentrations of JQ1 (G) or prostratin (H) for 24 h. The GFP expression was measured by flow cytometry and expressed as percentages of GFP(+) cells of the entire population. The error bars in all panels represent mean ± SD from three independent experiments, and the p values determined by the Student's t-test.",
    "ncbi_link": "DKC1: 1736"
  },
  {
    "caption": "B - Congo red plates with colonies of E. coli strain MC4100 relA+ and its target mutation csgD:M4-ompR:mut2 derivative, harboring sRNA-producing plasmids pOmrA, pOmrB, or an empty vector (pControl). Incubation at 28°C for 48 h.",
    "ncbi_link": "csgD: 
ompR: 
OmrA: 
OmrB: "
  },
  {
    "caption": "B - Relative fluorescence/OD600 of cells of E. coli strain MC4100 relA+ ∆omrAB or MC4100 relA+ ∆omrAB ∆hfq harboring the translational fusion plasmid pDgcM::GFP in combination with plasmids expressing OmrA, OmrB, or an empty control vector, after 16 h of growth at 37°C. Error bars SD, N=3. Average fluorescence intensities (a.u.)/ OD600 used to calculate ratios Note that absolute dgcM::gfp expression values are ≈3-4-fold lower in the ∆hfq strain",
    "ncbi_link": "dgcM: 
hfq: 
DgcM: 
GFP: 
gfp: 
omrA: 
OmrA: 
OmrB: "
  },
  {
    "caption": "C - Western blot analysis of cell lysates from strains MC4100 relA+ ∆omrAB harboring plasmids pOmrA, pOmrB, or mutant variants as indicated, in combination with a plasmid expressing C-terminal FLAG-tagged dgcM or dgcM_M2. As a loading control, part of a protein-stained gel is shown below.",
    "ncbi_link": "dgcM: 
omrA: 
OmrA: 
OmrB: "
  },
  {
    "caption": "A - Toeprinting showing inhibition of initiation complex formation on a truncated dgcM mRNA (210 nt from +1) by OmrA and OmrB. Inclusion of 30S ribosomes, tRNAfmet, OmrA, and OmrB is indicated. The unrelated IstR-1 sRNA is a negative control. The 30S/ tRNAfmet-dependent reverse transcription block (toeprint), is indicated by an arrow. Sequencing reactions were loaded next to the primer extension products (UCGA). The AUG start codon is indicated by asterisks.",
    "ncbi_link": "dgcM: 
IstR-1: 
OmrA: 
OmrB: "
  },
  {
    "caption": "B - In vitro translation of dgcM::3xflag mRNA in the presence or absence of OmrA/ OmrB, with or without purified Hfq protein, was carried out As an internal control, the non-target ompA::3xflag mRNA was included. The Western blot shows DgcM-3xFLAG and OmpA-3xFLAG protein levels.",
    "ncbi_link": "dgcM: 
flag: 
ompA: 
OmrA: 
OmrB: "
  },
  {
    "caption": "A - 5' end-labeled dgcM mRNA (10 nM) was subjected to probing All components added to the labeled RNA are indicated above the autoradiogram. When added, Hfq hexamers were at 50 nM, the sRNAs OmrA and OmrB at 250 nM. The accessibility of each nucleotide was probed with water (lanes 1-4, negative control for RNA integrity), RNase T1, or lead(II) acetate. Lane T1: RNase T1 under denaturing conditions. Lane OH: alkaline ladders. Binding sites of Hfq (green arrows and boxes), and site 1 (red arrows and boxes) and 2 (blue arrows and boxes) of the sRNAs, are highlighted. Note that site 2 is bound differently by OmrA and OmrB (blue boxes on gel). Black boxes indicate Hfq-dependent T1 cleavage enhancements.",
    "ncbi_link": "dgcM: 
OmrA: 
OmrB: "
  },
  {
    "caption": "Mobility shift assay with end-labeled dgcM RNA (210 nt species from +1) in the presence or absence of unlabeled OmrA or OmrB. When indicated, single-stranded DNA oligos were pre-annealed to site 1 (dgcM_site1), site 2 (dgcM_site2), or both, before addition of sRNAs. The additions for each sample are indicated above the Figure, and the identities of the nucleic acid complexes are indicated on the left for guidance.",
    "ncbi_link": "dgcM: 
OmrA: 
OmrB: "
  },
  {
    "caption": "Western blots showing DgcM-3xFLAG translated in vitro in the presence or absence of OmrA or OmrB. A - The inclusion of purified wild-type or mutant Hfq proteins is indicated, and the translation assay was conducted The different Hfq interaction site mutant proteins are indicated. Data information: Quantification of DgcM translation rates, relative to that of the unaffected OmpA control, is shown below the gels. The ratio of DgcM/ OmpA signal was set to unity for the lane lacking sRNA in each set of three combinations (-sRNA, +OmrA, +OmrB), indicated by \"1.00*\". Effects due to OmrA/ OmrB addition can be seen by comparing lanes 2 and 3 to lane 1 in each set.",
    "ncbi_link": "DgcM: 
FLAG: 
OmpA: 
OmrA: 
OmrB: "
  },
  {
    "caption": "Western blots showing DgcM-3xFLAG translated in vitro in the presence or absence of OmrA or OmrB. B - An ssDNA-oligo (Hfq_BS that base-pairs specifically to the Hfq binding site on dgcM mRNA (nt 42-66) was preannealed to the mRNA prior to OmrA/B addition and translation. OmpA-3xFLAG was included as internal control. Data information: Quantification of DgcM translation rates, relative to that of the unaffected OmpA control, is shown below the gels. The ratio of DgcM/ OmpA signal was set to unity for the lane lacking sRNA in each set of three combinations (-sRNA, +OmrA, +OmrB), indicated by \"1.00*\". Effects due to OmrA/ OmrB addition can be seen by comparing lanes 2 and 3 to lane 1 in each set.",
    "ncbi_link": "dgcM: 
DgcM: 
FLAG: 
Hfq: 
OmpA: 
OmrA: 
OmrB: "
  },
  {
    "caption": "A - Histograms show flow cytometry analysis of exponentially growing cells of E. coli strain MC4100 relA-, and its mutant derivatives hfq-F42A (hfq-prox), hfq-Y25D (hfq-dist), hfq-R16S_R17A_R19A_K47E (hfq-rim), ∆hfq, harboring the translational fusion plasmid pDgcM::GFP in combination with pOmrA, pOmrB, or a control vector. Data was obtained on a MACSQuant VYB instrument.",
    "ncbi_link": "DgcM: 
GFP: 
hfq: 
OmrA: 
OmrB: "
  },
  {
    "caption": "B - Northern blot analysis of total RNA isolated from the same cultures at the same time point as used for flow cytometry, probed for OmrA (strains containing pOmrA) or OmrB (strains containing pOmrB). 5S rRNA was used as loading control.",
    "ncbi_link": "OmrA: 
OmrB: "
  },
  {
    "caption": "(a) MCF7 cells stably expressing Myc-TEV-Flag-Beclin 1 (MEF-Beclin 1) and parental controls were lysed and subjected to MEF-tag-based purification. Proteins bound to MEF-Beclin 1 were isolated and detected by SDS-PAGE and silver staining. Seven bands specific for MEF-Beclin 1 are numbered. (b) Six bands were identified by nanoflow LC-MS/MS and MASCOT software.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(e) Gel filtration analysis. The supernatant fraction of A549 cell (or Atg14L knockdown) lysates were subjected to a Superose 6 column and each fraction was immunoblotted with the indicated antibody (see Supplementary Information, Fig. S2e). Relative amounts of each fraction determined by densitometry were plotted. Vo, void fraction. The elution pattern of each protein was reproduced in several experiments. Full scans of the gel and blots in a, c and d are available in Supplementary Information, Fig. S6.",
    "ncbi_link": "Atg14L: 22863"
  },
  {
    "caption": "(a) A549 cells were infected with adenovirus harbouring shRNA targeting Atg14L, Rubicon, UVRAG or a control (luciferase). Cell lysates were subjected to immunoblotting with the antibodies indicated. The asterisk in the Rubicon blot represents a non-specific cross-reacting band.",
    "ncbi_link": "luciferase: 
Atg14L: 22863
Rubicon: 9711
UVRAG: 7405"
  },
  {
    "caption": "(b) Quantification of GFP-positive dots per cell. Images were taken from cells shown in c and the number of GFP-positive dots was determined. At least 140 cells were counted per experiment and the values are mean ± s.d. of three independent experiments. (c) A monoclonal A549 cell line stably expressing GFP-LC3 was infected with adenovirus harbouring shRNA targeting Atg14L, Rubicon or control (luciferase). The cells were cultured under nutrient-rich or starvation conditions. GFP was observed by confocal laser microscopy. Scale bar, 10 μm. The full scan of the blot in a is available in Supplementary Information, Fig. S6.",
    "ncbi_link": "luciferase: 
Atg14L: 22863
Rubicon: 9711
LC3: 84557"
  },
  {
    "caption": "(a) Southern blot analysis of genomic DNA isolated from wild-type (WT, mAtg14L+/+) , mAtg14L+/- and knockout (KO, mAtg14L-/-) ES cells after digestion with PstI. Details of the probe are shown in Supplementary Information, Fig. S3.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "(c) The effect of Atg14L knockout on p62 turnover. WT, mAtg14L−/−, mAtg14L−/− + Atg14L, and mAtg5−/− ES cells were cultured in nutrient-rich (N) or starvation medium (S) for 3 h. Cell lysates were subjected to western blotting with the antibodies indicated.",
    "ncbi_link": "Atg14L: 
Atg5: 11793"
  },
  {
    "caption": "(d) Degradation of long-lived proteins is reduced in Atg14L knockout cells. WT, mAtg14L−/−, and mAtg5−/− ES cells were cultured in N or S medium or S medium with wortmannin (W, 100 nM) for 3 h and degradation of long-lived proteins was measured. The data are the mean ± s.d. of three independent experiments.",
    "ncbi_link": "Atg14L: 
Atg5: 11793"
  },
  {
    "caption": "(e) The effect of Atg14L knockout on LC3 turnover. WT, mAtg14L−/− and mAtg5−/− ES cells were cultured in N or S medium for 3 h in the presence or absence of E64d (50 μg ml−1) and pepstatin A (50 μg ml−1). Cell lysates were subjected to western blotting with the antibodies indicated. Full scans of the blots in b, c and e are available in Supplementary Information, Fig. S6.",
    "ncbi_link": "Atg14L: 
Atg5: 11793"
  },
  {
    "caption": "(a) The effect of Atg14L knockout (mAtg14−/−) on Atg16L dot formation. Wild-type (WT) and mAtg14−/− ES cells were cultured in nutrient-rich or starvation medium for 3 h. Cells were fixed and subjected to immunofluorescence with an anti-Atg16L antibody. Images of Atg16L staining (grey-scale) and Atg16L merged with Hoechst staining (colour) are shown.(c) Quantification of the number of Atg16L dots in a. The data are the mean ± s.d. of three independent experiments.",
    "ncbi_link": "Atg14: 
Atg14L: "
  },
  {
    "caption": "(b) The effect of Atg14L knockout on LC3 dot formation. WT and mAtg14L−/− ES cells were cultured in nutrient-rich or starvation medium for 3 h. Cells were fixed and subjected to immunofluorescence with anti-LC3 antibody. Images of LC3 staining (grey-scale) and LC3 merged with Hoechst staining (colour) are shown. Scale bars, 20 μm. (d) Quantification of the number of LC3 dots in b. The data are the mean ± s.d. of three independent experiments. For each of the experiments in c and d at least 13 cells were counted.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "(a) Immunofluorescence using an anti-Atg16L antibody. A549 cells were transfected with adenovirus expressing GFP-Atg14L and cultured in nutrient-rich or starvation medium for 4 h. Cells were fixed and stained with an anti-Atg16L antibody.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "(b) Immunofluorescence with an anti-LC3 antibody. A549 cells were transfected with adenovirus expressing GFP-Atg14L and cultured in starvation medium for 4 h. Cells were fixed and stained with an anti-LC3 antibody. Scale bar, 10 μm.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "d) Immunofluorescence with an anti-calnexin (ER) antibody. A549 cells transfected with adenovirus-based GFP-Atg14L. After 48 h, the cells were fixed and immunostained with calnexin (ER).Scale bar, 10 μm.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "(e) Immuno-EM analysis of GFP-Atg14L. A549 cells transfected with adenovirus-vector based GFP or GFP-Atg14L were subjected to immuno-EM analysis using an anti-GFP antibody. Scale bar, 500 nm. The arrows indicate the ER membrane and the arrowheads indicate the autophagosome membrane.",
    "ncbi_link": "Atg14L: "
  },
  {
    "caption": "(a) Double knockdown of Rubicon and Atg14L. A549 cells stably expressing GFP-LC3 were infected with adenovirus expressing either shRNA against Rubicon and Atg14L or control shRNA (luciferase). The image is available in Supplementary Information, Fig. S5a. The GFP-LC3 puncta were counted in nutrient-rich (N) or starvation (S) conditions. The data are mean ± s.d. of three independent experiments; at least 23 cells were counted for each experiment.",
    "ncbi_link": "Atg14L: 
luciferase: 
Atg14L: 100504663///22863
Rubicon: 9711
LC3: 84557"
  },
  {
    "caption": "(b) A549 cells were infected with adenovirus harbouring shRNA for Rubicon or control (luciferase). The cells were cultured in N or S medium in the presence or absence of E64d (50 μg ml−1) and pepstatin A (50 μg ml−1) for 1-4 h. Cell lysates were subjected to western blotting with the antibodies indicated.",
    "ncbi_link": "luciferase: 
Rubicon: 9711"
  },
  {
    "caption": "(c) Quantification of Atg16L puncta in Rubicon knockdown cells. The images are available in Supplementary Information, Fig. S5c. The data are mean ± s.d., n = 60 (60 cells, sample of Medium: N, shRNA: Control), n = 68 (68 cells, sample of Medium: S, shRNA: Control), n = 78 (78 cells, sample of Medium: N, shRNA: Rubicon), n = 83 (83 cells sample of Medium: S, shRNA: Rubicon).",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "d) Bulk degradation activity of Rubicon knockdown cells. The bulk degradation activity in control and Rubicon knockdown cells in nutrient-rich medium was measured. Wortmannin (W, 100 nM) was added as a negative control. The data are mean ± s.d. of three independent experiments.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(e) A549 cells infected with adenovirus harbouring shRNA for Rubicon and control (luciferase) were cultured in N or S medium for 4 h and cell lysates were subjected to immunoblotting with the antibodies indicated. Full scans of the blots in b and e are available in Supplementary Information, Fig. S6.",
    "ncbi_link": "luciferase: 
Rubicon: 9711"
  },
  {
    "caption": "(a) A549 cells transfected with a GFP-Rubicon expression plasmid and were subjected to immunofluorescence with various organelle marker antibodies. Scale bar, 10 μm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(b) A549 cells stably expressing GFP-LC3 were subjected to Rubicon knockdown (KD) and then transfected with mStrawberry, mStrawberry-Rubicon or mStrawberry-Rubicon mutant lacking the Beclin 1 binding region (Δ393849). Cells with strong expression of mStrawberry-Rubicon showed an overexpression-dependent dominant-negative phenotype; therefore, we selected cells with modest expression. The number of GFP-LC3 puncta was counted and mean ± s.d. are shown. mStrawberry, n = 12 (12 cells); mStrawberry-Mm-Rubicon, n = 14 (14 cells); mStrawberry-Mm-RubiconΔ393-849, n = 13 (13 cells).",
    "ncbi_link": "Beclin 1: 8678
Rubicon: 9711
LC3: 84557"
  },
  {
    "caption": "(a) The maturation of autophagosomes is enhanced in Rubicon knockdown cells. A549 cells stably expressing GFP-LC3, with Rubicon or control shRNA, were incubated in nutrient-rich medium with or without the protease inhibitors (PI) E64d (50 μg ml−1) and pepstatin A (50 μg ml−1) treatment for 4 h. The cells were stained with an anti-Lamp1 antibody (upper panels) and colocalization efficiency between GFP-LC3 and Lamp1 was counted (lower panel). The data are mean ± s.d. of 30 cells.",
    "ncbi_link": "Rubicon: 9711
LC3: 84557"
  },
  {
    "caption": "(b). Electron microscopy analysis of Rubicon knockdown cells. Control (luciferase) or Rubicon shRNA A549 cells grown in nutrient-rich medium was subjected to electron microscopy analysis (left panels). The arrows indicate autophagosomes and the arrowheads indicate autolysosomes. Scale bar, 1 μm. Autophagosomes and autolysosomes were counted in 21 cells, and the mean ± s.d. are shown (right panel).",
    "ncbi_link": "luciferase: 
Rubicon: 9711"
  },
  {
    "caption": "(c) EGFR degradation in Rubicon knockdown cells. Control or Rubicon shRNA A549 cells were treated with EGF (200 ng ml−1) for the indicated periods and the lysates were subjected to western blotting with the antibodies indicated (left panel). The band intensity was measured in three independent experiments and the mean ± s.d. are shown (right panel).",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(d) The effect of Rubicon overexpression in the turnover of EGF receptor. A549 cells were transfected with advenovirus-based GFP or GFP-Rubicon. After 24 h, EGF was added to cells expressing GFP-Rubicon or control GFP. At the times indicated, the cells were lysed and subjected to western blotting with the indicated antibodies.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(d) The effect of Rubicon overexpression in the turnover of EGF receptor. A549 cells were transfected with advenovirus-based GFP or GFP-Rubicon. After 24 h, EGF was added to cells expressing GFP-Rubicon or control GFP. At the times indicated, the cells were lysed and subjected to western blotting with the indicated antibodies.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(C) Immunoblot of cardiac GATA4 abundance in control (Con) and cardiomyocyte specific Gata4 knock-out mice (CM-G4-KO) at postnatal day (P) 1.(D) Quantification of the immunoblot shown in (C); *p=0.018.",
    "ncbi_link": "Gata4: 14463"
  },
  {
    "caption": "(E) Determination of cardiac gene-expression by qPCR 7 days after sham or cryoinjury for the indicated genes; *p=0.039 for Il13 and p=0.049 for Vegfa; **p=0.0043 for Ccne1, p=0.0027 for Cdk4, p=0.0096 for Cenpa, p=0.0015 for Zfp191; ***p=0.0009 for Ccna2, p=0.0002 for Cenpa.",
    "ncbi_link": "Ccna2: 12428
Ccne1: 12447
Cdk4: 12567
Cenpa: 12615
Il13: 16163
Vegfa: 22339
Zfp191: 59057"
  },
  {
    "caption": "(A) Representative immunoblots for GATA4 and GAPDH (as loading control) of fetal cardiomyocytes treated with adenoviruses (Ad) expressing control shRNA (shCon) or shRNA against Gata4 (shGATA4) for 48 hours.",
    "ncbi_link": "Gata4: 14463"
  },
  {
    "caption": "(A) Representative immunoblot for GATA4 and actin from neonatal cardiomyocytes treated with control (Ad.Con) or GATA4 expressing adenovirus (Ad.GATA4).",
    "ncbi_link": "GATA4: 14463"
  },
  {
    "caption": "(E) Representative pictures of myocardial sections immunostained for the indicated proteins from mice 7 days after cryoinjury and treatment with Ad.Con or Ad.GATA4. The quantification of cardiomyocytes (CM) staining positive for GATA4 vs. total cardiomyocytes is shown as bar graph (E´). The number within bars indicates the number of mice analyzed in that particular group. Scale bar: 20µm. ****p<0.0001.",
    "ncbi_link": "GATA4: 14463"
  },
  {
    "caption": "(E) Representative pictures of myocardial sections immunostained for the indicated proteins from mice 7 days after cryoinjury and treatment with Ad.Con or Ad.GATA4. The quantification of cardiomyocytes (CM) staining positive for GATA4 vs. total cardiomyocytes is shown as bar graph (E´). The number within bars indicates the number of mice analyzed in that particular group. Scale bar: 20µm. ****p<0.0001.",
    "ncbi_link": "GATA4: 14463"
  },
  {
    "caption": "(B) Quantification of left ventricular (LV) scar area of mice 7 days after cryoinjury and treated as indicated. The number within bars indicates the number of mice analyzed in that particular group. **p=0.0017 between Con and CM-G4-KO after PBS treatment and p=0.0078 between CM-G4-KO mice with PBS or IL-13 treatment.",
    "ncbi_link": "IL-13: 16163"
  },
  {
    "caption": "(D) Quantification of Ki67 or pH3 positive cardiomyocytes in mice treated as described in (A); *p=0.0106 and **p=0.0052 between Con and CM-G4-KO after PBS treatment and *p=0.0439 or **p=0.0023 between CM-G4-KO mice with PBS or IL-13 treatment.",
    "ncbi_link": "IL-13: 16163"
  },
  {
    "caption": " B. qRT-PCR analysis of NDIME expression during 7 days of neural differentiation (D3, P = 0.068; D5, P = 0.0049; D7, P = 0.0003). ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " C. Relative expression level of NDIME mRNA in the Sox1-GFP- population and Sox1-GFP+ population at day 7 of neural differentiation (P = 0.0118). ",
    "ncbi_link": "GFP: 
NDIME: 
Sox1: 20664"
  },
  {
    "caption": " D. mESCs were cultured in differentiation medium alone, or with 10% FBS, at day 5 of neural differentiation as shown by microscopy. Scale bars, 100 µm. E. Temporal expression profile of NDIME by qRT-PCR. mESCs were cultured in differentiation medium alone or with 10% FBS (D3, P = 0.074; D5, P = 0.0048; D7, P = 0.0034). ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " F. Distribution of NDIME in the cytoplasm and nucleus at day 7 of neural differentiation. The XIST RNA and GAPDH mRNA were considered as the positive controls for the nuclear and cytosolic fractions, respectively. Data are represented as mean, and error bars represent SEM in all panels. n= 3. ",
    "ncbi_link": "NDIME: 
GAPDH: 14433
XIST: 213742"
  },
  {
    "caption": " G. Verification of the efficiency of knockout of exon 3 of NDIME in mESCs via qRT-PCR. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " Knockout of NDIME strongly inhibited neural differentiation, as shown by microscopy analyses during 7 days of neural differentiation. Scale bars, 100 µm. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " I. Knockout of NDIME strongly inhibited neural differentiation, as shown by FACS analyses during 7 days of neural differentiation. Scale bars, 100 µm. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " J. Knockout of NDIME inhibits the expression of neural-lineage genes at day 5 of neural differentiation. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " L. NESTIN and GFP immunostaining of Ctrl, NDIME-/-, and NDIME-/-+Rs26-NDIME cells at day 5 of neural differentiation. Scale bars, 100 µm. ",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": "M. Expression of neural-lineage genes of Ctrl, NDIME-/-, and NDIME-/-+Rs26-NDIME cells at day 5 of neural differentiation.",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": " N. Relative expression of Emx1, Brn2, Sox5, and Zeb2 mRNA in different differentiation stages of Ctrl and NDIME-knockout cells (compared with control cells). ",
    "ncbi_link": "NDIME: 
Emx1: 13796
Brn2: 18992
Sox5: 20678
Zeb2: 24136"
  },
  {
    "caption": " A, Expression levels of MEF2C (D0, P = 0.0020; D3, P = 0.0025; D5, P = 0.0003; D7, P = 0.0142) of Ctrl and NDIME-/- cells during 7 days of neural differentiation, following knockout of NDIME at day 5 of neural differentiation. ",
    "ncbi_link": "NDIME: 
MEF2C: 17260"
  },
  {
    "caption": " B. (D0, P = 0.0020; D3, P = 0.0025; D5, P = 0.0003; D7, P = 0.0142) of Ctrl and NDIME-/- cells during 7 days of neural differentiation, and protein level of MEF2C following knockout of NDIME at day 5 of neural differentiation. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": "C. Western blot analysis of the effects of MEF2C overexpression in NDIME-knockout cells at day 5 of neural differentiation.",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " Overexpression of MEF2C in the NDIME-knockout cells rescued neural differentiation defects at day 5 of neural differentiation, as shown by microscopy ",
    "ncbi_link": "NDIME: 
MEF2C: 17260"
  },
  {
    "caption": " E. Overexpression of MEF2C in the NDIME-knockout cells rescued neural differentiation defects at day 5 of neural differentiation, as shown by FACS ",
    "ncbi_link": "NDIME: 
MEF2C: 17260"
  },
  {
    "caption": " G. Expression of neural-lineage genes in Ctrl, NDIME-/-, and NDIME-/-+Mef2c cells during 7 days of neural differentiation. ",
    "ncbi_link": "NDIME: 
Mef2c: 17260"
  },
  {
    "caption": "Enrichment of H3K27me3 at the Mef2c promoter in the NDIME-knockout cells at day 5 of neural differentiation compared with control cells.",
    "ncbi_link": "NDIME: 
Mef2c: 17260"
  },
  {
    "caption": "B. Enrichment of RNA polymerase II at the Mef2c promoter in the NDIME-knockout cells at day 5 of neural differentiation compared with control cells.",
    "ncbi_link": "NDIME: 
Mef2c: 17260"
  },
  {
    "caption": " C. NDIME interacts with EZH2 (P = 0.0043) and SUZ12 (P = 0.0003), but not EED (P = 0.6720) and EZH1 (P = 0.0951) compared with IgG, as determined by RIP using EZH2, SUZ12, EED, and EZH1 antibodies at day 5 of neural differentiation. Nuclear RNA U1 as a negative control. The presence of NDIME and U1 was measured by qRT-PCR with or without reverse transcriptase (RT). ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " NDIME levels following EZH2-RIP (P = 0.0028) in HEK293T cells compared with pcDNA3.1. Nuclear RNA U1 was used as a negative control. The presence of NDIME and U1 was measured by qRT-PCR with or without reverse transcriptase (RT). ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " E. NDIME levels following SUZ12-RIP (P = 0.0015) in HEK293T cells compared with pcDNA3.1. Nuclear RNA U1 was used as a negative control. The presence of NDIME and U1 was measured by qRT-PCR with or without reverse transcriptase (RT). ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " F, Enrichment of EZH2 at the Mef2c promoter in NDIME-knockout cells at day 5 of neural differentiation compared with control cells. ",
    "ncbi_link": "NDIME: 
Mef2c: 4208"
  },
  {
    "caption": " G. Enrichment of SUZ12 at the Mef2c promoter in NDIME-knockout cells at day 5 of neural differentiation compared with control cells. ",
    "ncbi_link": "NDIME: 
Mef2c: 4208"
  },
  {
    "caption": " H. Expression of neural-lineage genes at day 5 of neural differentiation in the NDIME-knockout cells after adding the EZH2 inhibitor GSK126 (7.5 µM) partially rescued neural differentiation defects, as shown by qRT-PCR; the wild-type and NDIME-knockout cells treated with DMSO. ",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": " B. RIP analysis using EZH2 antibody for the co-transfection of Flag-EZH2 and NDIME exons 1-3 (P = 0.0177) or exon 4 (P = 0.4335) in HEK293T extracts compared with IgG. ",
    "ncbi_link": "Flag: 
NDIME: 
EZH2: 14056"
  },
  {
    "caption": "C. Verification of the efficiency of overexpression of exons 1-3 or exon 4 of NDIME in NDIME-knockout cells at day 5 of neural differentiation via qRT-PCR. Three different primers P1, P2, and P3 were used to analyze NDIME or exons of NDIME expression in Ctrl, NDIME-/-, NDIME-/-+Rs26-Exon123, and NDIME-/-+Rs26-Exon4 cells (compared with control cells). The position of primers P1, P2, and P3 are shown in the schematic diagram.",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": " FACS , in Ctrl, NDIME-/-, NDIME-/-+Rs26-Exon123, NDIME-/-+Rs26-Exon4 cells at day 5 of neural differentiation. ",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": " E. , expression of neural-lineage genes , in Ctrl, NDIME-/-, NDIME-/-+Rs26-Exon123, NDIME-/-+Rs26-Exon4 cells at day 5 of neural differentiation. ",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": " F. Microscopy of the control, NDIME-/-, NDIME-/-+Rs26-Exon123, and NDIME-/-+Rs26-Exon4 cells at day 5 of neural differentiation. Scale bars, 100 µm. ",
    "ncbi_link": "NDIME: 
Rs26: 14910"
  },
  {
    "caption": "H. Enrichment of H3K27me3 at the Mef2c promoter of the cells in (F) at day 5 of neural differentiation.",
    "ncbi_link": "Mef2c: 17260"
  },
  {
    "caption": "A. Summary of the DEGs in the NDIME-knockout cells compared with control cells at day 5 of neural differentiation.",
    "ncbi_link": "NDIME: "
  },
  {
    "caption": "C. Summary of the DEGs in the MEF2C-knockdown cells compared with control cells at day 5 of neural differentiation.",
    "ncbi_link": "MEF2C: 17260"
  },
  {
    "caption": "I. Heatmap illustrating the expression of selected neurectoderm genes and mESCs-specific genes that were shown as log2 FPKM in Ctrl, NDIME-/- , shCtrl and shMef2c mESCs at day 5 of neural differentiation. Each lane corresponds to an independent biological sample.",
    "ncbi_link": "NDIME: 
Mef2c: 17260"
  },
  {
    "caption": " L. Relative expression of selectively down-regulated ASD risk genes from the DEGs of the NDIME-knockout cells compared with control cells at day 5 and from the DEGs of the MEF2C-knockdown cells compared with control cells at day 5. ",
    "ncbi_link": "NDIME: 
MEF2C: 17260"
  },
  {
    "caption": " A. qRT-PCR analysis of NDIME (P = 0.0051) and MEF2C (P = 0.0062) in VPA-treated mice and saline-treated mice; n = 9 per group. ",
    "ncbi_link": "NDIME: 
MEF2C: 17260"
  },
  {
    "caption": " B. Enrichment of EZH2 at the Mef2c promoter in VPA-treated mice and saline-treated mice (compared with saline-treated mice); n = 9 per group. ",
    "ncbi_link": "Mef2c: 17260"
  },
  {
    "caption": " G. Immunofluorescence images for GFP in the hippocampus of saline-treated mice, VPA-treated mice, and VPA-treated mice with viral-mediated expression of NDIME ",
    "ncbi_link": "GFP: 
NDIME: "
  },
  {
    "caption": " I-K. Adeno-associated virus overexpression of NDIME in the dentate gyrus (DG) of the dorsal hippocampus of VPA-treated mice rescued autism-like social deficits. Open field test (I), three-chamber test (J), and elevated-plus maze (EPM) test (K). Data in (I-K) are represented as mean ± SEM; n = 9 per group. Asterisks indicate a difference between VPA+AAV-GFP and Saline+AAV-GFP, whereas hash tags indicate a difference between VPA+AAV-NDIME-GFP and VPA+AAV-GFP. #P < 0.05, **/##P < 0.01, ***P < 0.001 (one-way ANOVA with Bonferroni post-hoc test). NS-non‐significant. ",
    "ncbi_link": "GFP: 
GFP.: 
NDIME: "
  },
  {
    "caption": "b - d) Comparative characterization of CHO cell bulk transfection cultures, selected for stable expression of the UnaG- or EGFP-encoding reporter constructs.b) Flow cytometry revealed efficient induction of green fluorescence, after treatment of both UnaG and EGFP-expressing CHO bulk cultures with CoCl2, while growth under hypoxia (1% oxygen) for 12 hours, selectively induced green fluorescence only in dUnaG expressing cells. Under normoxia (21% oxygen) only background fluorescence was observed.c) Assessment of the mean fluorescence intensity (MFI) to determine the activity of the 5xHRE-CMV promoter after 12 and 24hrs. Fluorescence intensity increased between 12 and 24hrs.",
    "ncbi_link": "HRE: 7422"
  },
  {
    "caption": "a) UnaG-based hypoxia sensing is applicable in vivo as shown here using the human Gli36 glioblastoma model. 500 Gli36 glioblastoma cells, constitutively expressing mCherry and stably transfected with the HRE-dUnaG sensor construct, were stereotactically transplanted into the cortex of a SCIDmouse. Shown is a 30 µm cryosection of a growing tumor 10 days after transplantation. Tumor cells are distinguished from the surrounding cortex by mCherry expression. Blood vessels were contrasted by immunostaining against PECAM-1. Expression of dUnaG was visualized by its green fluorescence and predominates in areas with reduced vascular density (outlined by white line in the composite panel (bottom right).b) Representative area from the tumor shown in a), which is located outside the viewfield in a) positioned more closely to the tumor border. Also at the tumor border UnaG-expressing cells are preferentially observed at a distance to PECAM-1+ vessels.",
    "ncbi_link": "HRE: 7422"
  },
  {
    "caption": "b) Microscopic assessment of the averaged fluorescence intensity (AFI) in CHO cells stably transfected with the dUnOHR sensor. Hypoxia was induced by incubation in 1% oxygen for 18 hrs, then the culture was switched to normoxia for 24 hrs, followed by another 14 hrs hypoxia and finally normoxia again. As expected UnaG fluorescence is efficiently induced under hypoxia, while mOrange fluorescence only appears after the switch to normoxia only. The increase in both green and orange fluorescence is limited under normoxia by the subsiding HRE-mCMV promoter activity. This behavior is repeated in subsequent hypoxia / normoxia cycles. The increase in absolute fluorescence intensity is due to proliferation during the 72hrs culture period. Plotted is the average of the mean ± SEM.c) Visualization of the fluorescence of the dUnOHR reporter during alternating hypoxia / normoxia cycles as described in b.) MIPs of life cell cultures stably transfected with the dUnOHR sensor construct illustrate the temporally asynchronous fluorescence of UnaG and mOrange. Scale bars = 100 µm.",
    "ncbi_link": "HRE: 7422"
  },
  {
    "caption": "B) Wildtype (BJ3505) and isogenic pmc1∆/vcx1Δ mutant cells were labeled with FM4-64. The number of vacuoles per cell was determined in 3 independent experiments evaluating 200 cells each. Scale bar: 2 µm. C) Frequency of visible fusion pores. Cells were grown as in (B). The percentage of cells showing visible fusion pore was determined from z-stacks. Means s.d. are shown for 100 stained vacuoles from 3 independent experiments. ",
    "ncbi_link": "pmc1: 852878
vcx1: 851429"
  },
  {
    "caption": "E) Distribution of Vph1-GFP and FM4-64 in vacuole-vacuole contact sites. Vph1-GFP expressing cells, labeled with FM4-64, were analyzed under a spinning disk confocal microscope equipped with two cameras for the simultaneous acquisition of GFP and FM4-64 fluorescence signals. Separate channels are shown on the right. The entire contact surface, but not the pore, is accessible to both probes. Scale bar: 2 µm.",
    "ncbi_link": "GFP: 
Vph1: 854444"
  },
  {
    "caption": "F) Expansion of a vacuolar fusion pore in real time. pmc1∆/vcx1Δ cells were labeled with FM4-64 and immobilized in a 50 µL flow chamber (Ibidi). The osmotic value of the medium was changed by perfusion with water, using a pump with a flow of 30 µL/s. A frame was acquired every 2 s for a total period of the 30 s, using the laser at minimal intensity.",
    "ncbi_link": "pmc1: 852878
vcx1: 851429"
  },
  {
    "caption": "A) Vacuolar membranes of wildtype (BY4741), nyv1∆ vam3∆, ypt7∆ or vma16F190Y cells were labeled with the vital dye FM4-64. A vacuole that was in a sufficiently peripheral location to be selectively photobleached was exposed to a laser pulse (white arrows indicate the bleaching area). Recovery of fluorescence in this area was assayed 10 seconds later by spinning disc confocal microscopy. Scale bar: 2 µm. B) Kinetics of FM4-64 recovery in (A). Means and s.d. are shown for 20 vacuole clusters from 3 independent experiments. ",
    "ncbi_link": "nyv1: 850782
vam3: 854273
vma16: 856421
ypt7: 855012"
  },
  {
    "caption": "C) In vivo lipid and content mixing. Vacuoles in living yeast were labeled with the indicated lumenal (CDCFDA) and membrane (FM4-64 or PX-GFP) probes. Note that CRY1 cells lack the ADE2 gene and hence naturally accumulate 5-amino-1-(5-phospho-D-ribosyl)imidazole as fluorescent fluid phase marker in the vacuolar lumen. FRAP-experiments were performed (arrows indicate the bleaching area). 1. Non-bleached lumenal area. 2. Bleached lumenal area. 3. Bleached membrane area. Scale bar: 2 µm. D and E) Kinetics of fluorescence recovery after photobleaching of the probes in (C). Numbers denote the areas shown in (C): 1. Non-bleached lumenal area. 2. Bleached lumenal area. 3. Bleached membrane area. Means and s.d. are shown for 20 vacuole clusters from 3 independent experiments. ",
    "ncbi_link": "ADE2: 854295"
  },
  {
    "caption": "C,D) FRAP assays for fusion pores. The indicated cells expressing (C) yeGFP-LT or (D) LT-yeGFP were labeled with FM4-64 and subjected to FRAP experiments Cells were imaged before and 0 (bleached) or 30 seconds after photobleaching (recovery). The bleached areas are indicated by an arrow. E,F) FRAP assays for fusion pores were performed as in (C, D), but with nyv1∆ cells. Scale bar: 2 µm. G) The histogram reports the fraction of cells showing FRAP. Means and s.d. are shown from 3 independent experiments, with 100 cells analyzed in each. ",
    "ncbi_link": "nyv1: 850782"
  },
  {
    "caption": "A-F) The indicated yeast strains were transformed with expression plasmids for FYVE2-GFP and their vacuolar membranes were labeled with FM4-64. FRAP was performed using a spinning disk microscope equipped with an emission beam splitter and two synchronized cameras, allowing to simultaneously analyze FM4-64 and GFP fluorescence. The histograms show the kinetics of signal recovery for (A) wildtype (WT), (B) vam3tsf, (C) ypt7T22N, (D) vma16F190Y, (E) vps33P184L, and (F) nyv1∆ cells. Scale bar: 2 µm. Arrows indicate the bleaching area. Means and s.d. are shown for 20 stained vacuoles from 3 independent experiments.",
    "ncbi_link": "GFP: 
nyv1: 850782
vam3: 854273
vma16: 856421
vps33: 851112
ypt7: 855012"
  },
  {
    "caption": "A-D) Wild-type (A, B) or nyv1∆ cells (C,D), which lack the vacuolar R-SNARE Nyv1, were labeled with FM4-64. Cells were immobilized on a chambered slide and subjected to FRAP experiments (C) Vacuole fission induced by hypertonic shift. FRAP experiments were performed before (0') or 15 min after addition of NaCl to 0.5 mol/l. The fluorescence images show the vacuoles inside a single cell. (B, D) Cells in S-phase were selected, which grow a daughter cell and therefore fission their vacuoles into a chain of tubulo-vesicular structures, part of which are transported into the daughter cell. FRAP experiment on vesicles in the inheritance structure were performed. Arrows indicate the bleaching area, dashed orange lines the cell cortex. Scale bar: 2 µm.",
    "ncbi_link": "nyv1: 850782
Nyv1: 850782"
  },
  {
    "caption": "A Western blot analysis of lysates from WT and MIC10 KO or MIC60 KO HAP1 cells. MIC10 KO cells show a drastic reduction of MIC13, MIC26 and MIC27 protein levels while protein levels of other MICOS components remain unchanged. MIC60 KO cells show a drastic reduction of protein levels of all MICOS components.",
    "ncbi_link": "MIC60: 10989
MIC10: 440574"
  },
  {
    "caption": "B Representative electron micrographs of WT, MIC10 KO and MIC60 KO HAP1 cells. Scale bar 500 nm.",
    "ncbi_link": "MIC60: 10989
MIC10: 440574"
  },
  {
    "caption": "C Quantification of CJs per mitochondrial section from different mitochondria in WT, MIC10 and MIC60 KO HAP1 cells using EM represented as boxplots. Boxplots show median and interquartile range from 25 to 75 percentile and whiskers represent minimum and maximum value. Data from n = 55-69 mitochondria (from 2 independent experiments) are shown as data points in the boxplots. ****P < 0.0001 (using unpaired Student's t-test).",
    "ncbi_link": "MIC60: 10989
MIC10: 440574"
  },
  {
    "caption": "D Quantification of cristae per mitochondrial section from different mitochondria in WT, MIC10 and MIC60 KO HAP1 cells using EM represented as boxplots. Boxplots show median and interquartile range from 25 to 75 percentile and whiskers represent minimum and maximum value. Data from n = 55-69 mitochondria (from 2 independent experiments) are shown as data points in the boxplots. ****P < 0.0001 (using unpaired Student's t-test).",
    "ncbi_link": "MIC60: 10989
MIC10: 440574"
  },
  {
    "caption": "E Comparison of oxygen consumption rates (pmol O2/s, normalized for cell numbers by Hoechst staining) of basal, proton leak, maximum and non-mitochondrial respiration in WT and MIC10 KO cells obtained from 3 independent experiments. The data is normalized to basal respiration from HAP1 WT. Bar and error bar represent mean ± SEM from 3 independent experiments. *P = 0.034 for basal (using one sample t-test) and *P = 0.018 for maximum respiration (using unpaired Student's t-test).",
    "ncbi_link": "MIC10: 440574"
  },
  {
    "caption": "F Comparison of oxygen consumption rates (pmol O2/s, normalized for cell numbers by Hoechst staining) of basal, proton leak, maximum and non-mitochondrial respiration in WT and MIC60 KO cells obtained from 3 independent experiments. The data is normalized to basal respiration from HAP1 WT. Bar and error bar represent mean ± SEM from 3 independent experiments. *P = 0.01 for basal (using one sample t-test), ***P = 0.0004 for maximum respiration and *P = 0.012 for non-mitochondrial respiration (using unpaired Student's t-test).",
    "ncbi_link": "MIC60: 10989"
  },
  {
    "caption": "A Representative STED super-resolution images of WT and MIC10 KO HAP1 cells immunostained with MIC60 or MIC10 antibodies (top panel) and TOMM70 (middle panel). Bottom panel shows merged images. Arrowheads show colocalization of MIC60 and TOMM70 punctae. Scale bar 500 nm.",
    "ncbi_link": "MIC10: 440574"
  },
  {
    "caption": "C FRAP curves (curve fitted) of MIC13 KO Hela cells expressing GFP-tagged fusion proteins of MIC60 (CJs), MIC10 (CJs), TOMM20 (OM), TIMM23 (IBM) and ATP5I (CM). Average FRAP curves (intensities in arbitrary units) for each marker were obtained (3 independent experiments, 6-10 mitochondria for each experiment). Error bars for each time point representing SEM are shown.",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "D Histogram showing average percentage of mobile fractions, obtained from curve fits of all mitochondria expressing GFP-tagged versions of MIC60 (CJs), MIC10 (CJs), TOMM20 (OM), TIMM23 (IBM) and ATP5I (CM) in WT and MIC13 KO Hela cells (data calculated from FRAP curves shown in Figure 3B and 3C that are obtained from 3 independent experiments, 6-10 mitochondria from each experiment).",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "A-D Representative single particle tracks of cells expressing MIC60- (A) and MIC10-SNAP (B) in WT Hela cells and MIC60- (C) and MIC10-SNAP (D) in MIC13 KO Hela cells, stained with silicone-rhodamine dye, and imaged at a rate of 33 ms/frame. Single tracks were colour-coded according to temporal appearance. Scale Bar 5 µm. Insets in each image show zoomed-in images of few representative tracks.",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "E Cumulative frequency of tracks having corresponding values of instantaneous diffusion coefficients (insD) in WT and MIC13 KO Hela cells expressing MIC60- and MIC10-SNAP stained with silicone-rhodamine. Number of tracks analysed (obtained from 2 independent experiments): n = 2541, 2540, 3560 and 1441 in WT Hela cells expressing MIC60-SNAP and MIC10-SNAP, MIC13 KO Hela cells expressing MIC60-SNAP and MIC10-SNAP, respectively. (****P ≤ 0.0001 for all possible comparisons, unpaired Student's t-test).",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "F Percentage of subtracks having directed motion in WT and MIC13 KO Hela cells expressing MIC60- and MIC10-SNAP and in WT and MIC60 KO HAP1 cells expressing MIC10-SNAP. Number of corresponding subtracks analysed (obtained from 2 independent experiments): n = 2561, 2443, 3402, 1360, 561 and 1110. Data are mean ± SEM. *P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001, unpaired Student's t-test.",
    "ncbi_link": "MIC60: 10989
MIC13: 125988"
  },
  {
    "caption": "A, C Representative live-cell STED super-resolution images (t=0 s) showing WT (A) and MIC13 KO (C) Hela cells expressing MIC10-SNAP stained with silicone-rhodamine. Box in (A and C) mark selection shown as a zoom in panel (B and D) respectively. Scale bar 500 nm. B, D Time-lapse image series of a mitochondrion expressing MIC10-SNAP in WT (B) and MIC13 KO (D) Hela cells (2.6 s/frame). Green and magenta asterisks show merging and splitting events of MIC10-SNAP respectively. Green arrows pointing inward connected by solid line and magenta arrows pointing outward connected by dotted line show sites of imminent merging and splitting events, respectively. Scale bar 500 nm.",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "E Blind quantification of merging and splitting events of CJs in WT and MIC13 KO Hela cells expressing MIC10-SNAP (3 independent experiments, 5-8 mitochondria for each experiment) represented as boxplots. Boxplots show median and interquartile range from 25 to 75 percentile and whiskers represent minimum and maximum value. *P = 0.026 (merging and splitting events in WT cells) and ****P < 0.0001 (merging and splitting events of WT vs. MIC13 KO), unpaired Student's t-test.",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "C Representative live-cell STED super-resolution images (t=0 s) showing MIC13 KO Hela cells expressing ATP5I-SNAP stained with silicone-rhodamine. Box marks selection shown as a zoom in panel (D). Scale bar 500 nm. D Time-lapse image series of a mitochondrion expressing ATP5I-SNAP in MIC13 KO Hela cells (2.5 s/frame). Green and magenta asterisks show merging and splitting events of cristae marked by ATP5I-SNAP respectively. Green arrows pointing inward connected by solid line and magenta arrows pointing outward connected by dotted line show sites of imminent merging and splitting events, respectively. Scale bar 500 nm. ",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "G Blind quantification of cristae merging and splitting events in WT and MIC13 KO Hela cells expressing ATP5I-SNAP (3 independent experiments, 3-7 mitochondria for each experiment) represented as boxplots. Boxplots show median and interquartile range from 25 to 75 percentile and whiskers represent minimum and maximum value. ****P < 0.0001, unpaired Student's t-test.",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "B Dual-colour STED super-resolution images of fused mitochondrion in WT Hela cells (Left Panel) showing colocalization of cristae marked with ATP5I-GFP (using anti-GFP antibody) and ATP5I-SNAP (stained with silicone-rhodamine). (Right Panel) Fused mitochondrion in MIC13 KO Hela cells showing cristae marked with either ATP5I-GFP (using anti-GFP antibody) or ATP5I-SNAP (stained with silicone-rhodamine). Arrowheads show merged cristae while arrows show cristae that maintain their individual identity. Scale bar 500 nm. C Boxplot showing quantification of colocalization events per µm of mitochondria in WT and MIC13 KO Hela cells. Boxplots show median and interquartile range from 25 to 75 percentile and whiskers represent minimum and maximum value. (15 mitochondria were taken from WT and MIC13 KO cells from 4 and 2 independent experiments, respectively, *P = 0.03, unpaired Student's t-test) ",
    "ncbi_link": "MIC13: 125988"
  },
  {
    "caption": "G-J Time-controlled knock-down of metabolic enzymes in the dorsal compartment of ubi-AT1.03NL wing discs using the apGalts driver. Images of FRET efficiency in control (G), apGalts>PfkRNAi (H), apGalts>GapdhRNAi (I), and apGalts>Glo1RNAi (J) wing discs after RNAi induction for 48 h (G), 120 h (H, J), and 93 hours (I). A rainbow colormap is used to indicate the FRET efficiency levels. Scale bars = 50 µm. K Line graphs showing the FRET efficiency in the ventral and dorsal compartment of individual control (n=27), apGalts>PfkRNAi (n=7), apGalts>GapdhRNAi (n=10), and apGalts>Glo1RNAi (n=6) wing discs. Loss of Pfk, Gapdh or Glo1 in the dorsal compartment of the wing disc reduces the levels of ATP. Paired t-test, ns= not significant, **p≤0.01, ***p≤0.001. ",
    "ncbi_link": "apGal: 
Gapdh: 32545///35728
Glo1: 35656
Pfk: 36060"
  },
  {
    "caption": "L Time-controlled knock-down of ecdysoneless (ecd) in the dorsal compartment of ubi-AT1.03NL wing discs using apGalts>ecdRNAi. Image of FRET efficiency in apGalts>ecdRNAi wing disc 48 h after RNAi induction. A rainbow colormap is used to indicate the FRET efficiency levels. Scale bars = 50 µm. M Line graph showing the FRET in the dorsal and ventral compartment of apGalts>ecdRNAi (n=28) wing discs. Loss of Ecd in the dorsal compartment of the wing disc reduces the levels of ATP. Paired t-test, ***p≤0.001. ",
    "ncbi_link": "apGal: 
ecd: 38291
Ecd: 38291
ecdysoneless: 38291"
  },
  {
    "caption": "A-D Adult wing phenotype of knock-down of Gapdh (C765>GapdhRNAi), over-expression of full-length Ecd (C765>ecd), over-expression of C-terminally truncated form of Ecd (C765>ecdDN), and knock-down of ecd (C765>ecdRNAi) in the whole wing disc (see Appendix Fig S3A for the expression pattern of C765-Gal4). Images of adult wings of control (A), C765>GapdhRNAi (A'), C765>ecd (B), C765>ecdDN (C), and C765>ecdRNAi (D) male flies. (A'') Overlay of the wings shown in A and A'. (C') Overlay of control wing and wing shown in C and C'. Loss of Ecd throughout the wing discs produces adults with vestigal wings (D). In contrast, the effects of ecdDN over-expression or Gapdh knock-down are less severe on tissue survival, giving rise to smaller wings with altered proportions. Images consist of a series of tiles that were stitched together by the microscope software. Scale bar= 500 μm. E, F Tukey box-and-whiskers plot showing quantifications of the area (E) and shape (aspect ratio: major/minor axis, F) of control, C765>GapdhRNAi, C765>ecd, and C765>ecdDN wings. Lower and upper hinges correspond to the first and third quartiles, vertical lines extend to ± 1.5 times the interquartile range. Sample size is indicated for each perturbation. Loss of Gapdh or over-expression of EcdDN leads to smaller wings that are increased along the anterior-posterior (A/P) axis compared to the proximal-distal (P/D) axis. Statistical analysis was performed using one-way ANOVA, followed by Dunnett's multiple comparisons test. ***p≤0.001. ",
    "ncbi_link": "Gal4: 
ecd: 38291
Ecd: 38291
Gapdh: 35728///32545
Gapdh: 32545///35728"
  },
  {
    "caption": " A-B' Time-controlled knock-down of ecd in the dorsal compartment of the wing discs (see Fig 1C for the expression pattern of apGalts). IF of control (A, A') and apGalts>ecdRNAi (B, B') wing discs, stained for the Hedgehog (Hh) pathway components Smoothened (Smo, A, B), and Ci155 (A', B'). Next to the images are quantifications of the respective staining in the dorsal versus ventral compartment of control (n=5) and apGalts>ecdRNAi (n=5) wing discs. Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Statistical analyses (t-test) revealed significant differences in Smo and Ci155 expression in the dorsal compartment between control and apGalts>ecdRNAi (Smo: p≤0.001, Ci155: p≤0.001) wing discs. Thus, loss of Ecd elevates Smo levels on the plasma membrane and increases the range of Ci155 stabilization in the anterior compartment. Wing discs were analyzed 48 h after RNAi induction. Scale bars= 50 μm. ",
    "ncbi_link": "apGal: 
Ecd: 38291
ecd: 38291"
  },
  {
    "caption": "C-E' Time-controlled knock-down of metabolic enzymes in the dorsal compartment of the wing disc. IF of apGalts>PfkRNAi, apGalts>GapdhRNAi, and apGalts>Glo1RNAi wing discs, stained for Smo (C, D, E) and Ci155 (C', D', E'). Next to the images are quantifications of the respective staining in the dorsal versus ventral compartment of apGalts>PfkRNAi (n=5), apGalts>GapdhRNAi (n=5), and apGalts>Glo1RNAi (n=6) wing discs. Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Statistical analyses (t-test) revealed significant differences in Smo and Ci155 expression in the dorsal compartment between control and apGalts>PfkRNAi (Smo: p≤0.001, Ci155: p≤0.01), apGalts>GapdhRNAi (Smo, Ci155: p≤0.05), or apGalts>Glo1RNAi (Smo: p≤0.001, Ci155: p≤0.05) wing discs. Thus, loss of Pfk, Gapdh or Glo1 elevates Smo levels on the plasma membrane and increases the range of Ci155 stabilization in the anterior compartment. Wing discs were analyzed 120 h after RNAi induction. Scale bars= 50 μm.",
    "ncbi_link": "apGal: 
Gapdh: 35728///32545
Gapdh: 32545///35728
Glo1: 35656
Pfk: 36060"
  },
  {
    "caption": " A-B Time-controlled knock-down of ecd in the dorsal compartment of the wing discs (see Fig 1C for the expression pattern of apGalts). IF of control (A) and apGalts>ecdRNAi (B) wing discs, stained for Hh. Next to the images are quantifications of the respective staining in the dorsal versus ventral compartment of control (n=4) and apGalts>ecdRNAi (n=5) wing discs. Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Statistical analysis (t-test) revealed no significant differences in Hh expression in the dorsal compartment between control and apGalts>ecdRNAi wing discs. Thus, loss of Ecd does not affect Hh production and spreading. Wing discs were analyzed 48 h after RNAi induction. Scale bars= 50 μm. ",
    "ncbi_link": "apGal: 
Ecd: 38291
ecd: 38291"
  },
  {
    "caption": "C-F Time-controlled knock-down of ecd in the dorsal compartment of dispatched mutant wing discs (dispS037707, apGalts>ecdRNAi, see Fig 1C for the expression pattern of apGalts). IF of control (C), apGalts>ecdRNAi (D), dispS037707 (E) and dispS037707, apGalts>ecdRNAi (F) wing discs expressing the decapentaplegic (dpp) reporter gene dpp-lacZ (dppZ), stained for dppZ. Next to the images are quantifications of the respective stainings (n=4 (C, F), n=5 (D), n=3 (E)). Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Statistical analyses (t-test) revealed a significant difference in dppZ expression in the dorsal compartment between control and apGalts>ecdRNAi (p≤0.01) (C vs D), and dispS037707 and dispS037707, apGalts>ecdRNAi (p≤0.01) wing discs (E vs F). Loss of Ecd elevates the expression of dppZ in a broader than normal stripe. However, lack of Ecd function alone is not sufficient to trigger dpp expression, which instead depends on the presence of Hh. Wing discs were analyzed 48 h after RNAi induction. Scale bars= 50 μm.",
    "ncbi_link": "apGal: 
disp: 44274
ecd: 38291
Ecd: 38291"
  },
  {
    "caption": " G-J IF of dispS037707 (G, I) and dispS037707, apGalts>ecdRNAi (H, J) wing discs, stained for Smo (G, H) and Ci155 (I, J). Next to the images are quantifications of the respective stainings (n=2 (G, H), n=3 (I), n=4 (J)). Graphs show mean (thick line) ± SD (thin lines). Dashed yellow lines indicate the position of the A/P boundary. Although statistical analyses (t-test) revealed no significant differences in Smo and Ci155 expression in the dorsal compartment between control and dispS037707, apGalts>ecdRNAi wing discs, loss of Ecd slightly induces an increased Smo accumulation and Ci155 stabilization independently of Hh. Wing discs were analyzed 48 h after RNAi induction. Scale bars= 50 μm. ",
    "ncbi_link": "apGal: 
disp: 44274
Ecd: 38291
ecd: 38291"
  },
  {
    "caption": " A-A''' Time-controlled knock-down of ecd or Gapdh in the dorsal compartment of the wing discs (see Fig 1C for the expression pattern of apGalts). The plasma membrane potential was detected using DiBAC4(3). The fluorescence intensity of DiBAC4(3) increases upon plasma membrane depolarization. (A) The change in plasma membrane potential upon genetic perturbation was quantified as the fold change in the ratio of DiBAC4(3) signal intensity in the dorsal to ventral compartment (control (n=19), apGalts>ecdRNAi (n=36) and apGalts>GapdhRNAi (n=18) wing discs). Error bars indicate ± SD. t-test, *p≤0.05, ***p≤0.001. (A'-A''') Representative images of DiBAC4(3) assay in control (A'), apGalts>ecdRNAi (A''), and apGalts>GapdhRNAi (A''') wing discs 48 h or 120 h after RNAi induction, respectively. V/D indicates the boundary between the ventral and dorsal compartments. Next to the maximal projections are shown the sum projections of cross-sections along the A/P axis. Loss of Ecd or Gapdh alters the plasma membrane potential. Scale bars= 50 μm. B Structure of the N-acylethanolamide analogue PAC-NAE. PAC-NAE contains a C15 fatty acid featuring diazirine and alkyne (red) modifications. C-C''' Time-controlled knock-down of ecd or Gapdh in the dorsal compartment of the wing discs (see Fig 1C for the expression pattern of apGalts). PAC-NAE uptake was quantified as the ratio of PAC-NAE signal intensity in the dorsal to ventral compartments. Shown is the fold change from control in apGalts>ecdRNAi and apGalts>GapdhRNAi wing discs (C). For each condition, dorsal/ventral PAC-NAE signal intensity was quantified for 5 wing discs. Error bars indicate ± SD. test-test, **p≤0.01, ***p≤0.001. (C'-C''') Representative images of PAC-NAE uptake in control (C'), apGalts>ecdRNAi (C'') and apGalts>GapdhRNAi (C''') wing discs at 48 h or 120 h after RNAi induction, respectively. Loss of Ecd or Gapdh blocks the uptake of PAC-NAE. Dashed green lines mark the D/V boundary. Scale bars= 50 μm.",
    "ncbi_link": "apGal: 
ecd: 38291
Ecd: 38291
Gapdh: 32545///35728"
  },
  {
    "caption": "MoLC from six different donors (n=6) were left untreated (NT) or incubated with LPS for 48h and analysed for S100A9 expression by RT-qPCR (left graph). MoLC treated as before were then transduced with HIV-GFP vectors for 48h and GFP+ cells were analysed by flow cytometry and data were graphically represented as fold relative to non-treated MoLC (right graph). Black horizontal line correspond to the mean. When applicable, student t-test was performed to determine statistical significance (***P<0.001).",
    "ncbi_link": "GFP: 
S100A9: 6280"
  },
  {
    "caption": "Cells transfected as above were pre-treated or not with nevirapine and transduced with HIV-GFP vectors for 48h. The percentage of GFP+ MoLC was analysed by flow cytometry. Data represent means values ± SD from two different donors.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Human epidermal cells treated as before were challenged for 48h with 20 and 200ng of p24 of HIV-Luc. When indicated cells were pre-treated with 10μM Nevirapine for 30 min before viral challenge. Luciferase activities measured in duplicates for each condition from two (infection with 20 ng P24) or three (infection with 200 ng P24) different skin samples were represented on a graph as means of relative luminescence units (RLU) ± SD.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "The experiment shown is representative of four donors for HIV-1-R5 (n=4) and three donors for HIV-1 primary isolates (n=3). Data collected from all donors were compiled and represented as bar charts for cells challenged with HIV-1-R5 and HIV-1 primary isolates. Nevirapine (Nev) (10μM) was used as control when indicated and data were represented as means ± SD of HIV-Gag+ cells from at least 2 (for siS100A9-MoLC infected by HIV-1 primary isolates) to 3 donors. When applicable, student t-test was performed to determine statistical significance (*P<0.1;**P<0.01;***P<0.001).",
    "ncbi_link": "S100A9: 6280"
  },
  {
    "caption": "E2C- and S100A9-expressing HEK293T cells were infected with the indicated MOI of HIV-GFP for 48h and GFP+ cells were analysed by flow cytometry. Mean values ± SD from four independent experiments (n=4) were normalized to the E2C-HEK293T control and represented in graph.",
    "ncbi_link": "E2C: 
GFP: 
S100A9: 6280"
  },
  {
    "caption": "E2C- and S100A9-expressing CHO cells were challenged with indicated MOI of MMLV-YFP vectors for 24h or 48h. The percentages of YFP+ CHO infected cells analysed by flow cytometry and data were represented on graphs.",
    "ncbi_link": "E2C: 
S100A9: 6280"
  },
  {
    "caption": "E2C- or S100A9-expressing THP1 were left uninfected (/) or infected for 3 h with the indicated p24 amounts of HIV-1 NL4-3/Nef-IRES-Renilla viruses containing BlaM-VPR. Cells were processed for Blam-Vpr assay and the percentage of cleaved CCF2 was analysed by flow cytometry. The mock condition corresponds to unstained E2C-expressing cells. Dot-plots from a representative experiment are shown.",
    "ncbi_link": "E2C: 
Nef: 
BlaM: 59687626
S100A9: 6280
VPR: 155807"
  },
  {
    "caption": "Schematic description of fate-of-capsid assay is displayed above. HEK293T expressing E2C or S100A9 were transduced with HIV-Luc (10ng p24) for 4 h. Cells were then subjected to the fate of capsid assay (see methods) in order to pull-down intact cores (CA cores) (recovered in the pellet). Equal volumes from the soluble (top fraction) and pelleted (down fraction) materials were analyzed by western blotting in order to evaluate the presence of p24 (CA), CypA, S100A9 and E2C proteins.",
    "ncbi_link": "E2C: 
Luc: 
S100A9: 6280"
  },
  {
    "caption": "Colorimetric HIV-1 RTase activity was performed with 10µg of immunoprecipitated and eluted E2C or S100A9 in presence of increasing MgCl2 concentrations. Means ± SD colorimetric data obtained from at least three independent experiments were normalized to E2C-containing conditions and shown on graphs.",
    "ncbi_link": "E2C: 
S100A9: 6280"
  },
  {
    "caption": "(A) The time courses of normalized FRET ratio (Mean ± SEM) of calcium biosensor before and after shockwave stimulation in HBSS Ca2+ medium with (yellow line, n = 6, N = 3) or without the Piezo1 expression (black line, n = 6, N = 3). (B) The representative FRET/ECFP ratio images of calcium biosensor in Piezo1-expressed HEK cells before (top left) and after (top right) LIS stimulation. Phase image with laser initiating point (left) and fluorescent image indicating Piezo1 expression (right) were also shown on the bottom panels (Scale bar, 40 μm). Color scale bars in the figures are to show the FRET/ECFP ratios, with cold and hot colors representing low and high ratios, respectively. (C) The time course of normalized FRET ratio (Mean ± SEM) of calcium biosensor in the Piezo1-expressing HEK cells before and after multiple shockwave stimulations in HBSS Ca2+ medium (n = 6, N = 3).",
    "ncbi_link": "Piezo1: 234839"
  },
  {
    "caption": "(A) The representative ECFP/FRET ratio images of FAK biosensor in Piezo1 overexpressed HEK cells before (left) and after (right) shockwave stimulation (Scale bar, 40 μm). Color scale bars in the figures are to show the ECFP/FRET ratios, with cold and hot colors representing low and high ratios, respectively. (B) The time courses of normalized ECFP/FRET ratio (Mean ± SEM) of FAK FRET biosensor before and after shockwave stimulation in HBSS Ca2+ media with (green line, n = 16, N = 3) or without Piezo1 (black line, n = 10, N = 3). (C) The percentage change of FRET ratio of the FAK FRET biosensor in HEK cells with or without Piezo1 after shockwave stimulation in HBSS Ca2+ medium. *P < 0.05 from student two-tailed t-test.",
    "ncbi_link": "Piezo1: 234839"
  },
  {
    "caption": "(A) The representative ECFP/FRET ratio images of FAK biosensor in Piezo1 expressing HEK cells before and after 25 μM Yoda1 stimulation (Scale bar, 10 μm). Color scale bars in the figures indicate ECFP/FRET ratios, with cold and hot colors representing low and high ratios, respectively. (B) The time courses of normalized FRET ratio (Mean ± SEM) of FAK FRET biosensor before and after Yoda1 stimulation with (pink line, n = 10, N = 3) or without Piezo1 (black line, n = 11, N = 3). The grey line represents the DMSO control group (n = 8, N = 3).",
    "ncbi_link": "Piezo1: 234839"
  },
  {
    "caption": "(C) The representative FRET/ECFP ratio images of the calcium biosensor in the Piezo1-expressing HEK cells before and after 25 μM Yoda1 stimulation (Scale bar, 10 μm). Color scale bars in the figures indicate FRET/ECFP ratios, with cold and hot colors representing low and high ratios, respectively. (D) The time courses of normalized FRET ratio (Mean ± SEM) of calcium biosensor in the Piezo1-expressing HEK cells (purple line, n = 9, N = 3) before and after 25 μM Yoda1 stimulation in culture medium.",
    "ncbi_link": "Piezo1: 234839"
  },
  {
    "caption": "(A)&(B), The time courses (Mean ± SEM) (A) and representative images (Scale bar, 10 μm) of FRET ratio of SHP2 biosensor (Y542F) before and after 25 μM or 0.5 μM Yoda1 stimulation in cells with or without Piezo1 overexpression (red bar, n = 5, N=3; blue bar, n = 5, N=3; purple bar, n = 11, N=3; green bar, n = 5, N=3).",
    "ncbi_link": "Piezo1: 234839"
  },
  {
    "caption": "D-E) Immunofluorescence  against CITRINE  (electroporated  cells), SOX10   (Schwann cell precursors and Schwann cells) and ISL1  (sensory  and sympathetic neurons) on embryos electroporated  with either control CRISPR  plasmid (D) or a CRISPR  plasmid containing a guide-RNA against Sox8  (E). CITRINE+ cells populate the developing dorsal root ganglia (DRG) and peripheral nerves. Examples of CITRINE+/SOX10+ cells shown by arrowheads. Asterisks show ventral boundary cap glia. Scale bar is 50 µm in overviews and 10 µm in insets. F) Quantification of the fate distribution of CITRINE+ cells as a % between glial  (SOX10+) cells, sensory neurons (ISL1+) or neither (SOX10-/ISL1-) in the DRG  of control and  Sox8KD chick embryos. Biological replicates - N=3 embryos  per condition (wild type versus Sox8  KD). Data represented as mean±SEM. Statistical significance determined using the Holm-Sidak method (alpha = 0.05) (multiple t-tests, unpaired). SOX10+ cells: p=0.7901, ISL1+ cells: p=0.9206, SOX10-/ISL1- cells: p=0.9206. For statistical significance: non-significant - p-value≥0.05. G) Quantification of (left) the % of SOX10+ cells in the peripheral nerves  that are CITRINE+ in control and Sox8KD chick embryos  and (right) the % of PH3+ CITRINE+ cells corresponding to proliferative  cells. Biological replicates - N=4 embryos  per condition for SOX10+ distribution and N=2 for PH3 quantification (wild type versus Sox8  KD). Data represented as mean±SEM. Statistical significance determined unpaired t-test with two-tailed p value. SOX10+ cells: p=0.0044, PH3+ cells: p=0.4929. For statistical significance: non-significant - p-value≥0.05, ** - p-value<0.01. Data information: In total, 6 embryos  were analyzed for the control electroporation  and 7 embryos  were analyzed for the Sox8  knock down electroporation  and data depicted in graphs correspond to mean±SEM per embryo  (corresponding to biological replicates): 3-4 electroporated embryos  were analyzed per condition (control and SOX8 knock down) with 4-5 sections stained  and analyzed per embryo  per region of interest (DRG, DRG: dorsal root ganglia, sg: sympathetic ganglion",
    "ncbi_link": "CRISPR: 
Sox8: 395483
SOX8: 395483"
  },
  {
    "caption": "I) Immunofluorescence  against CITRINE  (electroporated  cells), SOX10 (Schwann cell precursors  and Schwann cells) and TH  (sympathetic neurons and chromaffin cells) of the  sympathoadrenal domain on control and  Sox8KD embryos. CITRINE+/SOX10+ cells shown by empty arrowheads while CITRINE+/TH+ cells are shown by filled arrowheads. Scale bar = 50 µm. J) Quantification of the fate distribution of CITRINE+ cells as a % between glial  (SOX10+) cells, chromaffin cells  (TH+) or neither (SOX10-/TH-) in the proximity of the  dorsal aorta and  visceral nerve of wild type and Sox8  KD chick embryos. Biological replicates - N=4 embryos  per condition. Data represented as mean±SEM. Statistical significance determined using the Holm-Sidak method (alpha = 0.05) (multiple t-tests, unpaired). SOX10+ cells: p=0.0067, TH+ cells: p=0.0067, SOX10-/TH- cells: p=0.8819. For statistical significance: non-significant - p-value≥0.05, * - p-value<0.05. Data information: In total, 6 embryos  were analyzed for the control electroporation  and 7 embryos  were analyzed for the Sox8  knock down electroporation  and data depicted in graphs correspond to mean±SEM per embryo  (corresponding to biological replicates): 3-4 electroporated embryos  were analyzed per condition (control and SOX8  knock down) with 4-5 sections stained  and analyzed per embryo  per region of interest Sympathoadrenal domain).",
    "ncbi_link": "Sox8: 395483
SOX8: 395483"
  },
  {
    "caption": "(A-C) Measurement of autophagy during nutrient starvation in HT29 cells stably expressing YFP-LC3. (A) Increased LC3 puncta per cell following β‐catenin knockdown with siRNA compared with a non‐targeting (NT) control siRNA. Columns show autophagosome numbers (mean±s.e.m., n>200 cells in >20 fields of view per experiment of three independent treatments) assessed under normal and starved (2 h) conditions with β‐catenin or non‐targeting (NT) siRNA. Representative images (B) of YFP-LC3 puncta (green) and DAPI nuclei staining (blue) are shown. (C) Upper panel: western blotting showed increased LC3‐II expression in HT29 cells with β‐catenin knockdown compared to control cells after 2 h starvation. Lower panel: quantification of the LC3‐II/β‐actin ratio by densitometry (mean±s.e.m. of four independent treatments, *P=0.011 in nutrient conditions, *P=0.035 under starvation).",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(D and E) HCT116 β‐cateninWT/− cells overexpressing a control or β‐cateninS33Y plasmid nutrient starved for 24 h. (D) Immunostaining of LC3 (green) with DAPI nuclei staining (blue) showed decreased LC3 puncta with β‐cateninS33Y overexpression. (E) By western blotting, LC3‐II decreased with β‐cateninS33Y overexpression (upper panel). Lower panel: quantification of the LC3‐II/β‐actin ratio by densitometry (mean±s.e.m. of four independent treatments, *P=0.015).",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(F) Comparison of isogenic β‐cateninWT/− and β‐catenin−/ΔS45HCT116 cells. Upper panel: western blotting showed decreased LC3‐II in HCT116β‐catenin−/ΔS45 cells. Lower panel: western blotting confirmed by quantification using densitometry of the LC3‐II/β‐actin ratio (mean±s.e.m. of three independent treatments, *P=0.046).Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(A) Protein expression of p62 increased following β‐catenin knockdown under normal and starved conditions in HT29 cells.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(B) Comparison of HCT116 expression in isogenic HCT116β‐cateninWT/− and HCT116β‐catenin−/ΔS45 cells by western blotting showed decreased p62 expression in β‐catenin−/ΔS45 cells.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(C) LC3 puncta number per cell during starvation and nutrient addback post starvation. Left panel: LC3 puncta number reduces in non‐targeting (NT) siRNA control with nutrient addback. Right panel: LC3 puncta number reduces in β‐catenin knockdown cells with nutrient addback (mean±s.e.m. of three independent treatments; n>200 cells in >20 fields of view per experiment). Western blotting for β‐catenin confirmed knockdown.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(D) Western blotting of LC3 and p62 in HT29 cells following β‐catenin knockdown and starvation with lysosomal inhibitors. LC3‐II and p62 protein expression showed an increase with β‐catenin siRNA in the presence of autophagy flux inhibitors chloroquine (10 μM) or bafilomycin A1 (100 nM; applied for the final 30 min of the 8 h) compared to β‐catenin knockdown alone. Quantification by densitometry of the LC3‐II/β‐actin ratio (mean±s.e.m. of four independent experiments). See also Supplementary Figure S1A.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(A-D) LC3 staining (red) in mouse intestinal crypt and villus epithelium increased (white arrowheads) 2 days post β‐catenin deletion in β‐catenin−/lox‐villin‐creERT2 mice (C and D) compared to control β‐catenin+/lox‐villin‐creERT2 mice (A and B). Further magnification of the areas marked by white squares is shown (lower panels).",
    "ncbi_link": "cre: 
β‐catenin: 12387
ERT2: 13983"
  },
  {
    "caption": "(E-H)p62 staining (green) increased in the crypt and villus epithelium2 days after β‐catenin deletion in β‐catenin−/lox‐villin‐creERT2 mice (G and H) compared to control in β‐catenin+/lox‐villin‐creERT2 mice (E and F). DAPI staining (blue) identifies nuclei. β‐Catenin deletion was confirmed by immunofluorescence ( Supplementary Figure S1B). Red and green channel levels were adjusted post acquisition for clarity (equal level changes applied across the entire figure). Further magnification of the areas marked by white squares is shown (lower panels).",
    "ncbi_link": "cre: 
β‐Catenin: 12387
β‐catenin: 12387
ERT2: 13983"
  },
  {
    "caption": "(I and J) Western blotting on extracts from mouse intestinal epithelial tissue demonstrated increased p62 and LC3‐II protein expression 2 (I) and 4 (J) days post β‐catenin deletion in β‐catenin−/lox‐villin‐creERT2 mice compared to control β‐catenin+/lox‐villin‐creERT2 mice.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "cre: 
β‐catenin: 12387
ERT2: 13983"
  },
  {
    "caption": "(A) Relative p62/SQSTM1 mRNA levels by quantitative real‐time‐PCR (qRT-PCR) increased following β‐catenin knockdown in HT29 cells (mean±s.e.m., three independent experiments performed in triplicate, ***P0.001). β‐Catenin knockdown was confirmed by western blotting.",
    "ncbi_link": "β‐catenin: 1499
p62: 8878
SQSTM1: 8878"
  },
  {
    "caption": "(B) Relative p62 mRNA levels by qRT-PCR decreased with β‐cateninS33Yoverexpression after 24 h of starvation in HCT116 β‐cateninWT/− cells (mean±s.e.m., three independent experiments performed in triplicate, ***P0.001). β‐CateninS33Y overexpression was confirmed by western blotting.",
    "ncbi_link": "β‐catenin: 1499
p62: 8878"
  },
  {
    "caption": "(C) The increase in p62 protein expression induced by β‐catenin siRNA was attenuated in HT29 cells treated with 10 μg/μl cycloheximide and starvation for 8 and 24 h compared to vehicle control. A complementary experiment using the transcription inhibitor actinomycin D is shown in Supplementary Figure S1C.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(D) Overexpression of Fzd6 (green, left panel) increased p62 (red, right panel) protein expression in HEK293T cells. As an internal control, cells not overexpressing Fzd6 are shown in the field of view.",
    "ncbi_link": "Fzd6: 8323"
  },
  {
    "caption": "(E) Doxycycline induction (1 μg/ml) of DNTCF4 increased p62 and LC3‐II protein expression in doxycycline‐inducible DNTCF4 LS174T‐L8 cells. LGR5 downregulation by DNTCF4 confirmed inhibition of β‐catenin/TCF4 signalling.",
    "ncbi_link": "β‐catenin: 1499
TCF4: 6925"
  },
  {
    "caption": "(F) Relative p62 mRNA levels (48 h) by qRT-PCR increased following doxycycline induction of DNTCF4 in LS174T‐L8 cells (mean±s.e.m., three independent experiments performed in triplicate, ***P0.001).",
    "ncbi_link": "p62: 8878
TCF4: 6925"
  },
  {
    "caption": "(A) Chromatin immunoprecipitation (ChIP) demonstrates β‐catenin and TCF4 binding to the p62 promoter. HT29 cells were grown in normal or starvation conditions for 2 h and subjected to ChIP analysis with the indicated antibodies (IgG was used as a negative control). Binding of RNA Pol II, β‐catenin and TCF4 to the p62 promoter region was measured by quantitative PCR and expressed as percent enrichment relative to the input chromatin. During nutrient deprivation, binding of RNA Pol II to the p62 promoter increased; binding of β‐catenin to the p62 promoter decreased; TCF4 binding did not change (data are from one representative experiment of at least three independent experiments performed in triplicate). PCR products subjected to agarose gel electrophoresis are shown in Supplementary Figure S2A.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(B) Relative p62 mRNA expression by qRT-PCR increases ∼14‐fold after 24 h starvation in HT29 cells (mean±s.e.m., three independent experiments performed in triplicate, ***P0.001).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(C) Binding of acetyl‐Histone H3 to the p62 promoter increased under starvation conditions, suggesting p62 gene derepression (data are from one representative experiment of at least three independent experiments performed in triplicate).",
    "ncbi_link": "Histone H3: 8290
p62: 8878"
  },
  {
    "caption": "(D) Binding of β‐catenin to the p62 promoter (relative to β‐catenin binding to a non‐target gene promoter, GAPDH) significantly decreased under starvation conditions (mean±s.e.m., three independent experiments performed in triplicate, **P0.01).",
    "ncbi_link": "GAPDH: 
β‐catenin: 1499
p62: 8878"
  },
  {
    "caption": "(B) Autophagy decreased following Atg7 knockdown as shown by increased p62 and decreased LC3‐II protein expression. β‐Catenin protein expression increased following Atg7 siRNA. Reduction of LC3 puncta with Atg7 siRNA was confirmed by immunofluorescence and is shown in Supplementary Figure S2B.",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "(E, F) qRT-PCR shows reduction of Wnt‐target gene expression (E) Axin2 (*P=0.017) and (F) Cyclin D1 (**P=0.0036) after 8 h starvation (mean±s.e.m., three (Axin2) or six (Cyclin D1) independent experiments performed in triplicate).",
    "ncbi_link": "Axin2: 8313
Cyclin D1: 595"
  },
  {
    "caption": "(G-I) Inhibition of Wnt‐induced TopFlash activity by autophagy induction in (G) HCT116 β‐cateninWT/− cells (mean±s.e.m., three independent experiments performed in triplicate, **P0.01) and (H) RKO cells (mean±s.e.m., three independent experiments performed in triplicate, *P0.05). (I) Reduction of Wnt3a‐induced Cyclin D1 gene expression RKO cells after 12 h treatment with autophagy induction using starvation or PP242 (mean±s.e.m., two independent experiments).",
    "ncbi_link": "Cyclin D1: 595
β‐catenin: 1499"
  },
  {
    "caption": "(J, K) TopFlash activity following Atg7 knockdown in (J) HT29 cells (mean±s.e.m., four independent experiments performed in triplicate, *P=0.0488) and (K) RKO cells with 24 hWnt3a treatment (mean±s.e.m., three independent experiments performed in triplicate, *P=0.0282).",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "(L) A representative western blot of RKO cells following Wnt3a treatment and Atg7 siRNA.",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "(M) Relative β‐catenin mRNA levels did not change after 8 h starvation by qRT-PCR (mean±s.e.m., three independent experiments performed in triplicate).",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(P) Western blot analysis of RKO cells expressing a myc-tagged β‐catenin mutant (S33A, S37A, T41A, S45A) resistant to proteasomal degradation (myc-β‐cateninAAAA). RKO cells were subject to nutrient starvation for 2, 8 and 24 h, and autophagy induction was confirmed by increased LC3‐II and decreased p62 protein expression. Both endogenous β‐catenin and myc-β‐cateninAAAA protein expression decreased during starvation.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "LC3 and β‐catenin co‐localise in the mouseintestinal epithelium. (A and B) Immunofluorescence of LC3 (red) and β‐catenin (green) expression in the intestinal epithelium following 2 daystamoxifen treatment in control (A: β‐catenin+/lox‐villin‐creERT2) and β‐catenin deleted (B: β‐catenin−/lox‐villin‐creERT2) mice. (C and D) Magnified areas from B revealing co‐localisation of β‐catenin (red) and β‐catenin (green). Arrowheads indicate co‐localisation of LC3 and β‐catenin. (E) Linescan analyses from C and D showing staining intensity of indicated co‐localised puncta. Red and green channel levels were adjusted post acquisition (equal changes applied across the entire figure) and the blue channel was removed for clarity.",
    "ncbi_link": "cre: 
β‐catenin: 12387
ERT2: 13983"
  },
  {
    "caption": "(A) Co‐immunoprecipitation of YFP-LC3 or negative control YFP in HT29 cells. Binding of endogenous β‐catenin to YFP-LC3 was detected after 8 h of autophagy induction by starvation and starvation in the presence of lysosomal autophagy flux inhibitor chloroquine (10 μM). Input and immunodepleted lysates are shown.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(D) Pulldown assays using recombinant GST or GST-LC3B and lysates from HEK293 cells expressing HA-tagged wild‐type β‐catenin (HA-β‐cateninWT) or W504A/I507A β‐catenin (HA-β‐cateninW504A/I507A). HA-β‐cateninW504A/I507A exhibited reduced GST-LC3B binding compared to HA-β‐cateninWT.",
    "ncbi_link": "β‐catenin: 1499
LC3B: 81631"
  },
  {
    "caption": "(E) Recombinant myc-tagged His-LC3 (His-LC3-myc) interacted with recombinant GST-β‐cateninWTin vitro, but binding to GST-β‐cateninW504A/I507A was reduced (upper panel). Input recombinant proteins visualised with Coomassie blue are shown (lower panels).",
    "ncbi_link": "β‐catenin: 1499
LC3: 440738///81631///84557"
  },
  {
    "caption": "(F) Co‐immunoprecipitation experiments using lysates from HEK293 cells transiently expressing YFP-LC3 with β‐cateninWT or β‐cateninW504A/I507A starved for 8 h with chloroquine (10 μM). YFP-LC3 immunoprecipitated β‐cateninWT but not β‐cateninW504A/I507A. Input lysates are shown and immunoprecipitated p62 and YFP-LC3 served as positive controls.",
    "ncbi_link": "β‐catenin: 1499
LC3: 440738///81631///84557"
  },
  {
    "caption": "(G) HA-β‐cateninS33A/S37A/T41A/S45A/W504A/I507A (HA-β‐catenin6A) was more resistant to the starvation‐induced reduction in β‐catenin protein expression than HA-β‐cateninS33Y.",
    "ncbi_link": "β‐catenin: 1499"
  },
  {
    "caption": "(H) Relative cell death in HT29 cells subject to nutrient starvation for 24 h. Atg7 knockdown increased cell survival. The increase in cell survival following Atg7 knockdown was significantly reversed by simultaneously depleting β‐catenin (double knockdown of Atg7 and β‐catenin). Data are the mean±s.e.m. of three independent experiments performed in triplicate, ***P0.001; **P0.01.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Atg7: 10533
β‐catenin: 1499"
  },
  {
    "caption": "Diploid strain RBY1 and tetraploid strain RBY18 were cultured on YPD or PRE-SPO medium at 30°C or 37°C, respectively, for 7 days and plated onto 2-DOG medium to monitor for GAL1 loss.",
    "ncbi_link": "GAL1: 3644581"
  },
  {
    "caption": "Analysis of GAL1 loss (2-DOG resistant colonies) in tetraploid strain RBY18 after growth on PRE-SPO medium with or without antioxidants for 7 days at 37°C.",
    "ncbi_link": "GAL1: 3644581"
  },
  {
    "caption": "Assay to monitor for loss of GAL1 from tetraploid RBY18 overexpressing the indicated genes. Cells were grown for 7 d at 37°C on PRE-SPO medium in the presence (gene OFF) or absence (gene ON) of doxycycline (DOX).",
    "ncbi_link": "GAL1: 3644581"
  },
  {
    "caption": "Assay to monitor for loss of GAL1 (2-DOG resistant cells) arising from tetraploid strain RBY18 after culture at 37°C on SCD medium alone, SCD supplemented with HU (20 mM) or MMS (0.01%), or SCD medium with exposure to UV light for five seconds a day for 7 days.",
    "ncbi_link": "GAL1: 3644581"
  },
  {
    "caption": "2-DOG assay to monitor for loss of GAL1 function from tetraploid strain RBY18 after culture on SCD medium with or without PQT (600 μg/mL), H2O2 (2 mM), or PL (100 μg/mL) at 37°C for 7 d.",
    "ncbi_link": "GAL1: 3644581"
  },
  {
    "caption": "A Immunoblots  of AMPylated  proteins detected with a pan-AMP  antibody, BiP, FICD  and eIF2α  (a loading control) in lysates of  FICD∆ CHO  cells transiently transfected with plasmids encoding the indicated derivatives of FICD. Signals corresponding to AMPylated BiP, auto-AMPylated FICDE234G, total BiP, FICD  and eIF2α  are indicated. The novel species reactive with the anti-FICD  antiserum in lysates of cells transfected with plasmids expressing FICDR371S (*) likely reflects a glycosylated isoform arising from the creation of a new glycosylation site at Asn369.",
    "ncbi_link": "FICD: 100760999
FICD: 11153"
  },
  {
    "caption": "A Representative immunoblot of AMPylated  proteins in FICD∆ CHO  cells transiently transfected with expression plasmids encoding the indicated FICD  enzymes (replicated three times). Note that the hyperactive E234G mutant bearing the K124E-H131A mutations that compromise its ability to interact  with BiP, is nonetheless consistently auto-AMPylated.",
    "ncbi_link": "FICD: 100760999
FICD: 11153"
  },
  {
    "caption": "C Bar diagram of the amount of  alkaline phosphatase  [normalised to cytoplasmic luciferase    (a transfection marker)] secreted from FICD∆ CHO  cells co-expressing the indicated FICD  enzymes. The K124E-H131A mutations that interfere with engagement of BiP  as a substrate reverse the secretion defect imposed by the hyperactive FICD  enzymes [Mean ± SD, P values by ANOVA with Šídák's multiple comparisons test, n = 8-16 (biological replicates)].",
    "ncbi_link": "luciferase: 
alkaline phosphatase: 100771587
FICD: 100760999
FICD: 11153"
  },
  {
    "caption": "Lymphocyte subsets from 12 month old Ptpn2fl/fl;p53+/- and Lck-Cre;Ptpn2fl/f;p53+/- mice were analyzed by flow cytometry. Significance in (a) was determined using two-sided Fisher's exact test.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255
p53: 22059"
  },
  {
    "caption": "AT-3-OVA breast cancer cells were injected into the fourth inguinal mammary fat pads of female Ptpn2fl/fl and Lck-Cre;Ptpn2fl/fl mice and (c) tumour growth monitored over 26 days.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. Tumour-bearing Ly5.1+ mice were monitored for a) tumour growth over 21 days",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. After 21 days TILs were processed for flow cytometry and donor T cell numbers (Ly5.1-Ly5.2+) determined.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. After 9 days the proportion of Ly5.2+IFNγ+TNF+ versus Ly5.2+GrzB+ TILs was determined.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "AT-3-OVA mammary tumour cells (1x106) were injected into the fourth inguinal mammary fat pads of female Ly5.1+ mice. Seven days after tumour injection FACS-purified 2x106 naïve CD8+CD44loCD62Lhi lymph node T cells from Ly5.2+;OT-1;Ptpn2fl/fl versus Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred into tumour-bearing Ly5.1+ mice. d) for survival over 86 days.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Gene expression in tumours from mice treated with Ly5.2+;OT-1;Ptpn2fl/fl T cells 21 days post-adoptive transfer versus those re-emerging in mice treated with Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl T cells.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "B16.F10-OVA melanoma cells (1x105) were engrafted onto the abraded skin in the flanks of Ly5.1+ mice. 24 h after tumour cell engraftment naïve CD8+CD62LhiCD44lo lymph node T cells from Ly5.2+ OT-1;Ptpn2fl/fl versus Ly5.2+ OT-1;Lck-Cre;Ptpn2fl/fl mice were adoptively transferred and tumour incidence monitored.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "TILs were assessed for Ly5.2+;OT-1;Ptpn2fl/fl and Ly5.2+;OT-1;Lck-Cre;Ptpn2fl/fl donor T cell numbers by flow cytometry.",
    "ncbi_link": "OT-1: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "CD8+ HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes were stained for intracellular p(Y418)-SFK and p(Y418)-SFK MFIs were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-specific Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- CAR-T cells were incubated with HER-2 expressing 24JK sarcoma cells (24JK-HER-2) or HER-2 negative 24JK sarcoma cells and CD44, CD25, PD-1 and LAG-3 MFIs on CD8+ CAR-T cells were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, or Lck-Cre;Ptpn2fl/fl;Lck+/- HER-2 CAR-T cells were incubated with 24JK-HER-2 or 24JK sarcoma cells and the proportion of CD8+IFNγ+ versus CD8+IFNγ+TNF+ CAR-T cells determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl or Lck-Cre;Ptpn2fl/fl;Lck+/- HER-2 CAR-T cells were incubated with 5 μM CTV-labelled (CTVbright) 24JK-HER-2 and 0.5 μM CTV-labelled (CTVdim) 24JK sarcoma cells. Antigen-specific target cell lysis was monitored for the depletion of CTVbright 24JK-HER-2 cells by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-specific Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl and Lck-Cre;Ptpn2fl/fl;Lck+/- CAR-T cells were incubated with plate-bound α-CD3 and CD25 MFIs on CD8+CD44hiCD62Llo versus CD8+CD44hiCD62Lhi CAR-T cells determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl or Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Tgfb and Il10 mRNA levels in HER-2-E0771 tumours and mammary fat pads were assessed by quantitative real time PCR.",
    "ncbi_link": "Il10: 16153
Tgfb: 21803"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. f) 13 or g) six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with f) IL-2 (50,000 IU/day) or g) saline on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified Lck-Cre;Ptpn2fl/fl CD8+CD44hiCD62Lhi central memory HER-2 CAR-T cells. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for survival.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 tumours at day 10 post adoptive CAR-T cell transfer or from HER-2-E0771 tumours that had re-emerged after being cleared by Lck-Cre;Ptpn2fl/fl CD8+ HER-2 CAR-T cells were analyzed for HER-2 expression by immunohistochemistry. Scale bars: 200 μm (full size) and 70 μm (zoom).",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Normal mammary tissue or HER-2-E0771 tumours at day 10 post-adoptive CAR-T cell transfer, or from those had re-emerged after being cleared by Lck-Cre;Ptpn2fl/fl CD8+ HER-2 CAR-T cells were analysed for HER-2 expression by quantitative PCR.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 versus HER-2 negative E0771 breast cancer cells (2x105) were injected into the contralateral fourth inguinal mammary fat pads of female HER-2 TG mice 50 days after adoptive CAR-T cell transfer and mice were monitored for tumour growth.",
    "ncbi_link": "HER-2: 2064"
  },
  {
    "caption": "Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells isolated from the spleens of HER-2 TG mice at f) 70 days",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells isolated from the spleens of HER-2 TG mice at g) 10 days post adoptive transfer were stained for CD8, CD44 and CD62L and analysed by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Lymphocytes were isolated from the tumours and dLN at day 10 post adoptive transfer and mCherry+CD45+CD3+CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. CTV-labelled CD8+ HER-2 CAR-T cells were incubated with 24JK-HER-2 or 24JK sarcoma cells and CTV dilution assessed by flow cytometry to monitor proliferation.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. CXCR3 MFIs on CD8+CD44hiCD62Lhi versus CD8+CD44hiCD62Llo CAR-T cells (c) and CXCR5, CCR7, CCR5 MFIs on CD8+CD44hiCD62Lhi CAR-T cells (d) were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Cxcl9 and Cxcl10 mRNA levels in HER-2-E0771 tumours were assessed by quantitative real time PCR.",
    "ncbi_link": "Cre: 2777477
Cxcl10: 15945
Cxcl9: 17329
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Lymphocytes were isolated from HER-2-E0771 tumours at day 3 post adoptive CAR-T cell transfer and mCherry+CD45+CD3+CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Lck+/- or Lck-Cre;Ptpn2fl/fl;Stat5fl/+ HER-2 CAR-T cells were incubated with plate-bound α-CD3 and CXCR3 MFIs on CD8+CD44hiCD62Llo CAR-T cells determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
Stat5: 20851///20850"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer. Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl;Stat5fl/+ HER-2 CAR-T cells were incubated with plate-bound α-CD3 and stimulated with murine recombinant IL-2 and IL-15 for the indicated time points. Intracellular p(Y694)-STAT-5 MFIs in CD8+CD44hiCD62Llo were determined by flow cytometry.",
    "ncbi_link": "CAR-T cells: 
Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
Stat5: 20851///20850"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth. Lymphocytes were isolated from the tumours on day 3 post adoptive transfer and mCherry+CD45+ CD8+ CAR-T cell numbers were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
Stat5: 20851///20850"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
Stat5: 20851///20850"
  },
  {
    "caption": "HER-2-E0771 mammary tumours cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 6x106 FACS-purified CD8+CD62LhiCD44hi central memory HER-2 CAR-T cells generated from Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl, Lck-Cre;Ptpn2fl/fl;Stat5fl/+ or Lck-Cre;Ptpn2fl/fl;Lck+/- splenocytes. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and monitored for tumour growth. Lymphocytes were isolated from the tumours on day 16 post adoptive transfer and mCherry+CD45+ CD8+ CAR-T cell numbers were determined by flow cytometry. In (c) TILs were stained for intracellular IFNγ and TNF after PMA/Ionomycin treatment.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
Stat5: 20851///20850"
  },
  {
    "caption": "HER-2-E0771 cells generated to inducibly overexpress PTPN2 in response to doxycycline (E0771-HER-2-PTPN2hi) were pre-incubated (24 h) with vehicle or doxycycline (DOX) subsequently stimulated with IFNγ for the indicated times. STAT-1 Y701 phosphorylation (p-STAT-1) and PTPN2 levels were assessed by immunoblotting.",
    "ncbi_link": "PTPN2: 19255"
  },
  {
    "caption": "Cxcl9 and Cxcl10 mRNA levels in vehicle versus DOX-treated and IFNγ-stimulated HER-2-E0771 cells were assessed by quantitative real time PCR.",
    "ncbi_link": "Cxcl10: 15945
Cxcl9: 17329"
  },
  {
    "caption": "E0771-HER-2-PTPN2hi mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Five days after tumour injection mice were administered vehicle or DOX in drinking water followed by irradiation (4 Gy) on day 6 and the adoptive transfer of 6x106 FACS-purified central memory Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells. Mice were then injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer In (g) CD45+CD8+mCherry+ TILs were quantified by flow cytometry at day 4 post adoptive transfer.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
PTPN2: 19255
Ptpn2: 19255"
  },
  {
    "caption": "E0771-HER-2-PTPN2hi mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Five days after tumour injection mice were administered vehicle or DOX in drinking water followed by irradiation (4 Gy) on day 6 and the adoptive transfer of 6x106 FACS-purified central memory Ptpn2fl/fl versus Lck-Cre;Ptpn2fl/fl HER-2 CAR-T cells. Mice were then injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and (h) tumour growth was monitored.",
    "ncbi_link": "Cre: 2777477
HER-2: 2064
Lck: 16818
Ptpn2: 19255
PTPN2: 19255"
  },
  {
    "caption": "HER-2 CAR-T cells generated from C57BL/6 and Lck-Cre;Ptpn2fl/fl splenocytes were transfected with GFP versus Ptpn2 siSTABLE™ FITC-conjugated siRNAs and intracellular PTPN2 levels were determined by flow cytometry.",
    "ncbi_link": "GFP: 
Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "c-d) HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 HER-2 CAR-T cells generated from C57BL/6 splenocytes transfected with GFP versus Ptpn2 siSTABLE™ FITC-conjugated siRNAs two days before adoptive CAR-T cell transfer. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and tumour growth was monitored.",
    "ncbi_link": "GFP: 
HER-2: 2064
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 HER-2 CAR-T cells generated from C57BL/6 splenocytes transfected with GFP versus Ptpn2 siSTABLE™ FITC-conjugated siRNAs two days before adoptive CAR-T cell transfer. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 after adoptive CAR-T cell transfer and tumour growth was monitored. CD45+CD3+CD8+ mCherry+ CAR-T cells numbers were determined in HER-2-E0771 positive tumours and spleens by flow cytometry 21 days post adoptive transfer.",
    "ncbi_link": "GFP: 
HER-2: 2064
Ptpn2: 19255"
  },
  {
    "caption": "HER-2 CAR-T cells generated from C57BL/6 and Lck-Cre;Ptpn2fl/fl splenocytes were transfected with Cas9 and control or Ptpn2 sgRNAs using the Lonza 4D-Nucleofector and after two days intracellular PTPN2 levels determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Lck: 16818
Ptpn2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 control HER-2 CAR-T cells or those in which PTPN2 had been deleted by CRISPR RNP. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and tumour growth monitored.",
    "ncbi_link": "HER-2: 2064
PTPN2: 19255"
  },
  {
    "caption": "HER-2-E0771 mammary tumour cells (2x105) were injected into the fourth inguinal mammary fat pads of female HER-2 TG mice. Six days after tumour injection HER-2 TG mice received total body irradiation (4 Gy) followed by the adoptive transfer of 10x106 control HER-2 CAR-T cells or those in which PTPN2 had been deleted by CRISPR RNP. Mice were injected with IL-2 (50,000 IU/day) on days 0-4 post adoptive CAR-T cell transfer and tumour growth monitored. g) CD45+ CD8+ mCherry+ CAR-T cells numbers were determined in HER-2-E0771 tumours by flow cytometry 19 days post adoptive transfer.",
    "ncbi_link": "HER-2: 2064
PTPN2: 19255"
  },
  {
    "caption": "(B, C) Exercise capacity of MCK-KO and WT mice from the low intensity regiment was conducted. (n = 4 WT, n = 5 KO mice, mean ±SEM, * p < 0.05, two-tailed student's t-test).",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "(E, F) Exercise capacity of MCK-KO and WT mice from the high intensity regiment (n = 5 mice, means ± SEM, two-tailed student's t-test).",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "(A) The H&E staining of MCK-KO and WT soleus muscle after a bout of low intensity treadmill running (top 40X, bottom 100X magnifications). Black arrow indicates centralized nuclei. (B) The percentage of myofibers with centralized nuclei was determined by manual counting 300 myofibers in 20X magnification. (n = 3, means ± SEM, * p < 0.05, two-tailed student's t-test). ",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "(C-D) The analogous set of data is shown with WT and MCK-KO GA muscles. (n = 3, means ± SEM, two-tailed student's t-test. GA: Gastrocnemius)",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "Hydrogen peroxide (H2O2) levels were measured in WT and MCK-KO soleus (E) at rest and after a bout of exercise (n = 6 per group, means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing).",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "(A-D) Succinate dehydrogenase staining was performed in WT and MCK-KO soleus at sedentary (A, B) and after a bout of low-intensity exercise for 50 min (C, D) (10X, 20X magnifications), and the staining intensity was quantified using ImageJ (n = 6, means ± SEM, * p < 0.05, two-tailed student's t-test). (E-H) The analogous set of data is shown with WT and MCK-KO GA muscles. (n = 6, means ± SEM, * p < 0.05, two-tailed student's t-test). (I-L) The analogous set of data is shown with WT and MCK-KO EDL muscles. (n = 6, means ± SEM, two-tailed student's t-test. EDL: Extensor digitorum longus) ",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "(M, N) Mitochondrial respiration was measured in WT and MCK-KO soleus tissue after a bout of low-intensity exercise for 50 min under basal conditions and in response to 4 mM oligomycin (complex V inhibitor), 4 mM FCCP (uncoupler), or 4 mM each of rotenone and antimycin A (complex I inhibitor) (n = 8, means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing). (O, P) Mitochondrial respiration was measured in Dnmt3a knocked down L6 myotubes which were transduced with lentiviral under basal conditions and in response to 4 mM oligomycin (complex V inhibitor), 4 mM FCCP (uncoupler), or 4 mM rotenone and antimycin A (complex I inhibitor) (n = 5, means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing).",
    "ncbi_link": "MCK: 12715
Dnmt3a: 13435"
  },
  {
    "caption": "(E, F) ALDH1L1 protein expression and the quantification in WT vs. MCK-KO soleus, GA and EDL muscles at sedentary and normalizing to GAPDH using ImageJ.",
    "ncbi_link": "MCK: 12715"
  },
  {
    "caption": "Single and double knockdowns of Dnmt3a and Aldh1l1 in L6 myotubes were achieved by lentiviral transduction. NADPH levels (H) and NOX activity (I) were measured in single and double knockdowns of Dnmt3a and Aldh1l1 in L6 myotubes. (n = 3, means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing).",
    "ncbi_link": "Aldh1l1: 107747
Dnmt3a: 13435"
  },
  {
    "caption": "(J, K) H2O2 levels were measured in single and double knockdowns of Dnmt3a and Aldh1l1 in L6 myotubes. (J: n = 3 and K: n = 6 for Control, Aldh1l1 KD, Aldh1l1 KD + Dnmt3a KD, n = 5 for Dnmt3a KD, means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing).",
    "ncbi_link": "Aldh1l1: 107747
Dnmt3a: 13435"
  },
  {
    "caption": "(D, E) mitochondrial respiration in Dnmt3a knockdown and control L6 myotubes treated with NAC (3mM) or vehicle treatment for 24hrs (n = 5 Control groups n = 3 Dnmt3a KD, n = 4 Dnmt3a KD with NAC treatment groups. means ± SEM, * p < 0.05, two-tailed student's t-test and two-way ANOVA followed by Bonferroni post-hoc testing).",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "(D, E) Exercise capacity of WT and MCK- KO with or without transfection of gCont vs. gAldh1l1 under the low intensity regimen (n = 4 WT + gCont, n = 9 MCK- KO + gCont, and MCK- KO + gAldh1l1, *p<0.05, means ± SEM, two-tailed student's t-test and one-way Anova).",
    "ncbi_link": "Aldh1l1: 107747
MCK: 12715"
  },
  {
    "caption": "(C) Immunohistochemistry of sections from a C9orf72 patient and a healthy control. Monoclonal anti-GA and antiserum from Ova-GA vaccinated mice detect neuronal cytoplasmic inclusions (arrows) in the molecular layer of the cerebellum. Note that crude antiserum shows higher background than the monoclonal antibody. Scale bar indicates 20 μm. (D) Quantitative analysis for GA-positive inclusions per 100 neurons in (C). One-way ANOVA, Tukey's post hoc test, F(3,15)=2.676, p=0.0846, C9: Anti-GA 1A12 vs C9: TG-Ova-(GA)10 serum p=0.9483.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(E) Immunohistochemistry of sections from occipital cortex of a C9orf72 patient and a healthy control with monoclonal anti-GA and antiserum preincubated with 0.1 mg/ml recombinant GST-(GA)15 or GST. Scale bar indicates 20 μm.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(A) Analysis of motor function in vaccinated GA-CFP mice and wild-type littermates in a beam walk assay. Average time to cross the beam from duplicate repeat measurements in consecutive weeks. Pairwise Wilcoxon rank sum test with Benjamini-Hochberg correction. All comparisons with WT-PBS and the TG-Ova-(GA)10 mice vs. TG-PBS comparison are depicted with * p<0.05, **, p<0.01.",
    "ncbi_link": "CFP: "
  },
  {
    "caption": "TIGAR regulates intracellular ROS levels in response to nutrient starvation or metabolic stress. (A) ROS levels in U2OS cells stably over-expressing Flag-tagged-TIGAR (clones TIGAR#5 and TIGAR#7) or control cells (clones Cont#1 and Cont#3) left untreated, after 6 h of nutrient starvation or 24 h of metabolic stress. ROS levels were measured by flow cytometry after DCF treatment. The results are expressed as the mean DCF fluorescence (and standard deviation), from three independent experiments.",
    "ncbi_link": "TIGAR: 57103"
  },
  {
    "caption": "TIGAR regulates intracellular ROS levels in response to nutrient starvation or metabolic stress.(B) Basal, nutrient starvation-induced (5 h) or metabolic stress-induced (18 h) ROS levels in U2OS cells in the presence of either scrambled, TIGAR siRNA1 or TIGAR siRNA2, measured by flow cytometry after DCF treatment. The results are expressed as the mean intensity of cell fluorescence (and standard deviation). * represents significant difference from control conditions (P<0.05).",
    "ncbi_link": "TIGAR: 57103"
  },
  {
    "caption": "TIGAR expression modulates autophagy in response to nutrient starvation or metabolic stress. (A) (Left panel) confocal microscopy images of the fluorescence in U2OS cells stably over-expressing Flag-tagged-TIGAR (clone TIGAR#7) or control cells (clone Cont#1) and infected with an adenovirus expressing GFP-LC3 for 16 h. Cells were then left untreated, exposed to nutrient starvation for 6 h or to metabolic stress for 24 h. (Right panel) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta from three independent experiments. The mean values with standard deviation are presented.",
    "ncbi_link": "LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "TIGAR expression modulates autophagy in response to nutrient starvation or metabolic stress.(B) (Left panel) Confocal microscopy images of the fluorescence in U2OS cells stably expressing GFP-LC3 and transfected with scrambled or TIGAR siRNAs. After 48 h transfection, cells were then left untreated, exposed to nutrient starvation for 5 h or to metabolic stress for 18 h. (Right panel) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta from three independent experiments. The mean values with standard deviation are presented.",
    "ncbi_link": "LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "TIGAR expression modulates autophagy in response to nutrient starvation or metabolic stress. (C) (Left panel) Western blot showing the expression levels of endogenous LC3-I, LC3-II and TIGAR in U2OS cells transfected with scrambled or TIGAR siRNAs, and 48 h later exposed to nutrient starvation for 0, 2.5 and 6 h. (Middle panel) Western blot showing the expression levels of endogenous LC3-I, LC3-II and TIGAR in U2OS stably over-expressing Flag-tagged-TIGAR (clones TIGAR#5 and TIGAR#7) or control cells (clones Cont#1 and Cont#3) and left untreated. (Right panel) Western blot showing the expression levels of p62, COX-IV and TIGAR in U2OS cells transfected with scrambled or TIGAR siRNAs and left untreated. Actin expression was examined as a loading control.",
    "ncbi_link": "TIGAR: 57103"
  },
  {
    "caption": "TIGAR expression modulates autophagy independently of p53. (A) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta. U2OS cells stably expressing GFP-LC3 were transfected with scrambled or TIGAR siRNAs, and 48 h after transfection, cells were left untreated (t0) or treated with Bafilomycin A1 (100 nM) for 1 or 2 h (t1 and t2). The percentage of cells with GFP-LC3 puncta was calculated at the indicated time points. Data are shown as the mean and standard deviation from three independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "(B) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta. U2OS cells stably expressing GFP-LC3 were cotransfected with scrambled or TIGAR siRNAs, and scrambled or p53 siRNA. After 48 h transfection, cells were left untreated or exposed for 5 h to nutrient starvation. The percentage of cells with GFP-LC3 puncta was calculated, and data are shown as the mean and standard deviation from three independent experiments.",
    "ncbi_link": "TIGAR: 57103
p53: 7157"
  },
  {
    "caption": "(C) Western blot showing the expression levels of endogenous p53 and TIGAR in U2OS cells cotransfected with scrambled or TIGAR siRNAs, and scrambled or p53 siRNA, and 48 h later exposed to nutrient starvation for 5 h. Actin expression was examined as a loading control.",
    "ncbi_link": "TIGAR: 57103
p53: 7157"
  },
  {
    "caption": "(D) Quantitation of the percentage of GFP-LC3-positive cells displaying GFP puncta. U2OS cells stably expressing GFP-LC3 were cotransfected with scrambled or TIGAR siRNAs, and scrambled or DRAM siRNA1/2. After 48 h transfection, cells were left untreated or exposed for 5 h to nutrient starvation. The percentage of cells with GFP-LC3 puncta was calculated, and data are shown as the mean and standard deviation from three independent experiments; * represents significant difference from starved control conditions (P<0.05); @ represents significant difference from untreated control conditions (P<0.05); # represents a lack of significant difference from control conditions (P>0.05).",
    "ncbi_link": "DRAM: 55332
TIGAR: 57103"
  },
  {
    "caption": "(C) Quantitation of the percentage of GFP-LC3 puncta positive cells. U2OS cells stably expressing GFP-LC3 were transfected with vector pCHER1A expressing the mCherry gene as control, or expression plasmids for Flag-tagged-TIGAR or HA-tagged-FBPase-2. After 48 h transfection, cells were left untreated, exposed to nutrient starvation for 6 h or to metabolic stress for 24 h, with or without treatment with AO1 (NAC (2 mM) and L-ascorbic acid (2 mM)) for 24 h. The percentage of cells with GFP-LC3 puncta was calculated, and data are shown as the mean and standard deviation from three independent experiments.",
    "ncbi_link": "FBPase-2: 114508
TIGAR: 57103"
  },
  {
    "caption": "(D) Quantitation of the percentage of GFP-LC3 puncta positive cells. Cells were left untreated, exposed to nutrient starvation for 6 h with or without treatment with AO1 (NAC (2 mM) and L-ascorbic acid (2 mM)), AO2 (glutathione ethyl ester (4 mM)) or AO3 (ethyl pyruvate (4 mM)) for 24 h. U2OS cells stably expressing GFP-LC3 were transfected with vector pCHER1A expressing the mCherry gene as control, or expression plasmid for Flag-tagged-TIGAR. After 48 h transfection, cells were treated. The percentage of cells with GFP-LC3 puncta was calculated, and data are shown as the mean and standard deviation from three independent experiments.",
    "ncbi_link": "TIGAR: 57103"
  },
  {
    "caption": "(E) (Left panel) Quantitation of the percentage of GFP-LC3 puncta positive cells. Cells were left untreated, exposed to nutrient starvation for 5 h or to metabolic stress for 18 h, with or without treatment with AO1 (NAC (2 mM) and L-ascorbic acid (2 mM)) for 24 h. U2OS cells stably over-expressing GFP-LC3 in the presence of either scrambled, TIGAR siRNA1 or TIGAR siRNA2. (Right panel) Basal or nutrient starvation-induced (5 h) ROS levels in U2OS cells in the presence of either scrambled, TIGAR siRNA1 or TIGAR siRNA2 with or without treatment with AO1 (NAC (2 mM) and L-ascorbic acid (2 mM)) for 24 h, measured by flow cytometry after DCF treatment. The results are expressed as the mean intensity of cell fluorescence (and standard deviation). * represents significant difference from control conditions (P<0.05); # represents a lack of significant difference from control conditions (P>0.05).",
    "ncbi_link": "LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "(A) Western blot showing knockdown of ATG5 protein expression by ATG5 siRNA.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(B) RT-PCR showing knockdown of ATG10 mRNA expression by ATG10 siRNA.",
    "ncbi_link": "ATG10: 83734"
  },
  {
    "caption": "(C) Quantitation of the percentage of GFP-LC3 puncta positive cells. U2OS cells stably over-expressing GFP-LC3 in the presence of either scrambled, TIGAR siRNA1 or TIGAR siRNA2, and either scrambled, ATG5 siRNA or ATG10 siRNA. After 48 h, cells were left untreated or exposed to nutrient starvation for 5 h.",
    "ncbi_link": "ATG10: 83734
ATG5: 9474
LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "(D) ROS levels in U2OS cells in the presence of either scrambled, TIGAR siRNA1 or TIGAR siRNA2, and scrambled, ATG5 siRNA or ATG10 siRNA, measured by flow cytometry after DCF treatment. After 48 h, cells were left untreated or exposed to nutrient starvation for 5 h. The results are expressed as the mean intensity of cell fluorescence (and standard deviation). * represents significant difference from control conditions (P<0.05); # represents a lack of significant difference from control conditions (P>0.05).",
    "ncbi_link": "ATG10: 83734
ATG5: 9474
TIGAR: 57103"
  },
  {
    "caption": "(A) Quantitation of the percentage of GFP-LC3 puncta positive cells. U2OS cells stably over-expressing Flag-tagged-TIGAR (clones TIGAR#5 and TIGAR#7) or control cells (clones Cont#1 and Cont#3) were left untreated or exposed to nutrient starvation for 6 h, with or without treatment with Z-VAD-FMK for 24 h. The percentage of cells with GFP-LC3 puncta was calculated, and data are shown as the mean and standard deviation of the mean from three independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557
TIGAR: 57103"
  },
  {
    "caption": "(B) Apoptosis in U2OS cells stably over-expressing Flag-tagged-TIGAR (clones TIGAR#5 and TIGAR#7) or control cells (clones Cont#1 and Cont#3), as measured by cells with a sub-G1 DNA content. Cells were transfected with either scrambled, TIGAR siRNA1 or TIGAR siRNA2. Cells were left untreated, exposed to nutrient starvation for 6 h or to metabolic stress for 24 h.",
    "ncbi_link": "TIGAR: 57103"
  },
  {
    "caption": "(C) Apoptosis in U2OS cells cotransfected with scrambled or TIGAR siRNAs, and scrambled, ATG5 siRNA or ATG10 siRNA, as measured by cells with a sub-G1 DNA content. After 48 h, cells were left untreated, exposed to nutrient starvation for 6 h or to metabolic stress for 24 h. Data are shown as the mean and standard deviation from three independent experiments. In each case, the increase in apoptosis after knockdown of ATG5 or ATG10, compared with the matched control, was statistically significant; * represents significant difference from control conditions (P<0.05); # represents a lack of significant difference from control conditions (P>0.05).",
    "ncbi_link": "ATG10: 83734
ATG5: 9474
TIGAR: 57103"
  },
  {
    "caption": "Validation of the selected genes uncovered from global RNAseq analyses by qRT-PCR analyses displays up-regulation of CXCL-6 after LPS treatment.",
    "ncbi_link": "CXCL-6: 6372"
  },
  {
    "caption": "Validation of the selected genes uncovered from global RNAseq analyses by qRT-PCR analyses displays up-regulation of , IL-8 and IL-1β after LPS treatment.",
    "ncbi_link": "IL-8: 3576
IL-1β: 3553"
  },
  {
    "caption": "Representative microphotographs of TLR4 silenced and non-silenced MSCs primed with LPS and co-cultured with neutrophils. Immunostaining was performed with an antibody detecting NETs (DNA-histone, red). Of note, TLR4 silenced MSCs upon LPS priming cannot mount any adaptive response and fail to enhance NET formation (lower row, outer right panel) as compared to non-silenced, LPS primed MSCs co-cultured with PMA activated neutrophils (lower row, outer left panel). Neutrophils and DMSO served as a negative control (upper row, outer left panel), while neutrophils activated by the protein C kinase activator PMA served as a positive control depicting enhanced NET formation (upper row, middle panel). Co-culture with MSCs suppressed enhanced NET formation (upper row, outer left panel) induced by PMA. Scale bars: 50μm.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "Quantitative assessment of NET bound elastase employing a specific ELISA in identical experimental setting as described in Figure 1. Similarly, to immunostaining, a significant reduction of NET bound elastase was observed in TLR4 silenced LPS primed MSCs when co-cultured with activated neutrophils as opposed to high NET bound elastase in non-silenced LPS primed MSCs co-cultured with activated neutrophils. Statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, three biological replicates.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "High resolution scanning electron microscope analysis depicting enhanced NET formation (red arrows) expulsed from neutrophils (blue arrows) in the presence of LPS primed MSC co-cultured with PMA activated neutrophils (middle row, outer left panel) as compared to reduced NETs in non-primed MSCs co-cultured with activated neutrophils (middle row, outer right panel). Of note, TLR4 silenced LPS primed MSCs failed to activate neutrophils and NETs (lower row, outer left panel). TLR4 silenced and non-primed MSCs display reduced NETs in co-cultures with activated neutrophils (lower row, outer right panel), suggesting that PMA activation shares TLR4 signaling components. PMA activated neutrophils alone served as positive control with highly enhanced NETs (upper row, outer right panel) and DMSO treated neutrophils as negative controls (upper row, outer left panel). Red stars indicate neutrophil derived granules. Scale bars: 0.1µm",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "Representative clinical pictures of murine wounds at 0, 3, 5, 7 and 10 days after wounding. Enhanced wound healing in LPS primed MSCs group as opposed to all other groups. Statistical analysis of 20 wound areas per group at the indicated time points, expressed as percentage of the initial wound size (day 0), for PBS control, non-primed MSCs, LPS primed MSCs, non-primed scrambled siRNA-treated (Scr) MSCs, LPS primed Scr MSCs and LPS primed TLR4 silenced MSCs. Results are mean ± SD of five biological replicates representing 1 of 3 independent experiments. Statistical analysis was performed using one way ANOVA.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "Representative photomicrographs of confocal microscopy of sections from differently injected day 1 wounds stained for Ly6G+ neutrophils (green) and F4/80+ macrophages (red). Nuclei are stained with DAPI (blue). Double staining was performed for sections of day 1 wounds injected with PBS (control), non-primed MSCs, LPS primed MSCs and LPS primed TLR4-silenced MSCs Double stained cells indicate phagocytic engulfment of neutrophils by macrophages. To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Scale bar: 100µm.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "Representative photomicrographs of confocal microscopy of sections from differently injected day 3 wounds double-stained for TGFβ-1 (red) and for F4/80+ macrophages (green). Nuclei are stained with DAPI (blue). Double staining was performed for sections of day 5 wounds injected with PBS (control), non-primed MSCs, LPS primed MSCs and LPS primed TLR4-silenced MSCs. Scale bar: 50µm. Representative photomicrographs of sections of day 5 wounds immunostained for CD31 (indicative of endothelial cells and newly formed vessels) and for α-SMA (indicative of myofibroblasts differentiation) after injection of LPS primed MSCs, non-primed MSCs, LPS primed TLR4-silenced MSCs or PBS (middle and lower panel). To facilitate comparison, areas inside the rectangles are shown at 5x magnification in the insets. Scale bars: 50µm.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "Quantitative analysis of CD31 positive endothelial cells in sections of wounds injected with PBS, non-primed MSCs, LPS primed MSCs and LPS primed TLR4 silenced LPS Cell counting was performed on immunostained wound sections and statistical analysis was performed using one way ANOVA, values are represented as mean ± SEM, six biological replicates.",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "  (C) Electrophoretic mobility-shift assay (EMSA) with biotin-labeled RORA consensus, rs2978980T or rs2978980G probes and HGC-27 or MGC80-3 nuclear extracts. HGC-27 or MGC80-3 left panel: EMSA with RORA consensus or rs2978980T probes. Lane 1-8: from the first lane at the left side to the right side. Lanes 4 and 8, probe only; lanes 2 and 6, probe and nuclear extracts; lanes 1, 3, 5 and 7, probe and nuclear extracts plus 100× unlabeled rs2978980T (lanes 1 and 5) or RORA consensus probes (lanes 3 and 7). HGC-27 or MGC80-3 right panel: EMSA with rs2978980T or rs2978980G probes. Lanes 1 and 6, probe only; lanes 2 and 7, probe and nuclear extracts; lanes 3-5 and 8-10, probe and nuclear extracts plus 100× unlabeled rs2978980T (lanes 5 and 8), rs2978980G (lanes 3 and 10) or RORA consensus probes (lanes 4 and 9).  ",
    "ncbi_link": "RORA: 6095"
  },
  {
    "caption": " (F) Suppression of RORA using siRNAs (siRORA-1 and siRORA-2) could markedly down-regulate lncPSCA expression in MGC80-3 cells but not in HGC-27 cells. In detail, MGC80-3 and HGC-27 cells were transfected with siRORA-1 and siRORA-2, lncPSCA and RORA expression levels were measured by RT-qPCR and Western Blot. ",
    "ncbi_link": "PSCA: 8000
RORA: 6095"
  },
  {
    "caption": " (E) lncPSCA-knockout significantly promoted growth of MGC80-3 (n = 8) or HGC-27 (n = 7) xenografts compared with control xenografts after 27 or 18 days. ",
    "ncbi_link": "PSCA: 8000"
  },
  {
    "caption": " (B) lncPSCA inhibits invasion abilities of MGC80-3 and HGC-27 cells. Cells on the lower surface of the chamber were stained by crystal violet. Scale bar = 100 μm. ",
    "ncbi_link": "PSCA: 8000"
  },
  {
    "caption": " (C) In MGC80-3 and HGC-27 cells, expression changes of different markers (β-catenin, ZO-1, SNAIL and VIMENTIN) of epithelial-to-mesenchymal transition were examined after overexpression or knockout of lncPSCA. ",
    "ncbi_link": "PSCA: 8000"
  },
  {
    "caption": " (F) Gastric cancer cells after lncPSCA-knockout or stably overexpressing lncPSCA and control cells were treated with cycloheximide (CHX) or vehicle for the indicated periods of time. DDX5 levels were analyzed by Western blot. ",
    "ncbi_link": "PSCA: 8000"
  },
  {
    "caption": " (I) Knockdown of DDX5 with siRNA (siD-1 and siD-2) substantially reduced the proliferation of gastric cancer cells. Data show one representative example of three biological replicates. (J) Silencing of DDX5 with shRNA (shD) significantly reduced the proliferation of gastric cancer cells. Data show one representative example of three biological replicates. ( ",
    "ncbi_link": "DDX5: 1655"
  },
  {
    "caption": " (E) RNA Pol II ChIPseq and RNAseq signals of PMAIP1, CDKN1A, SESN2 and SESN3 in HGC-27 cells. Red bars represent the RNA Pol II ChIPseq signal. Orange or blue bars represent the RNAseq signals of HGC-27 cells overexpressing lncPSCA (lncP) or with silenced DDX5 (shD), respectively. ",
    "ncbi_link": "CDKN1A: 1026
DDX5: 1655
PMAIP1: 5366
PSCA: 8000
SESN2: 83667
SESN3: 143686"
  },
  {
    "caption": " (F) Validation of candidate downstream genes of the lncPSCA-DDX5 axis identified through the integrated analyses. qRT-PCR was performed for PMAIP1, CDKN1A and SESN2 genes upon overexpression of lncPSCA (lncP), silencing of DDX5 (shD) or lncPSCA konckout. Error bars indicate the SEM. Data show one representative example of three biological replicates. ",
    "ncbi_link": "CDKN1A: 1026
DDX5: 1655
PMAIP1: 5366
PSCA: 8000
SESN2: 83667"
  },
  {
    "caption": "Time course of the mRNA levels of main downstream antioxidant targets of Nrf2 during the transition from productive (3-9 dpi) to latent (14 dpi) infection, as measured by qPCR Data in (G) are depicted as mean±SEM of 3 biological replicates. raw data were first normalized using 18S as housekeeping control and then expressed as Log2 fold mRNA expression in infected vs mock infected cells Trx= thioredoxin; NQO1= NAD(P)H [quinone] dehydrogenase 1; HMOX-1= heme oxygenase 1; G6PD= glucose-6-phosphate dehydrogenase; GCLC= glutamate-cysteine ligase ; TrxR1= thioredoxin reductase 1. ",
    "ncbi_link": "18S: 
G6PD: 2539
glucose-6-phosphate dehydrogenase: 2539
GCLC: 2729
heme oxygenase 1: 3162
HMOX-1: 3162
Nrf2: 9817
NAD(P)H [quinone] dehydrogenase 1: 1728
NQO1: 1728
thioredoxin: 7295
Trx: 7295
thioredoxin reductase 1: 7296
TrxR1: 7296"
  },
  {
    "caption": "(I) Relative mRNA expression of Nrf2 downstream antioxidant targets in J-Lat 9.2 cells left untreated (latent) or treated for 24h with 10µM TPA (reactivated). Data are depicted as mean±SEM of 3 biological replicates. raw data were first normalized using 18S as housekeeping control and then expressed as Log2 fold mRNA expression in TPA-reactivated vs latent cells Trx= thioredoxin; NQO1= NAD(P)H [quinone] dehydrogenase 1; HMOX-1= heme oxygenase 1; G6PD= glucose-6-phosphate dehydrogenase; GCLC= glutamate-cysteine ligase  ; TrxR1= thioredoxin reductase 1.",
    "ncbi_link": "18S: 
G6PD: 2539
glucose-6-phosphate dehydrogenase: 2539
GCLC: 2729
heme oxygenase 1: 3162
HMOX-1: 3162
NAD(P)H [quinone] dehydrogenase 1: 1728
NQO1: 1728
thioredoxin: 7295
Trx: 7295
thioredoxin reductase 1: 7296
TrxR1: 7296"
  },
  {
    "caption": "(A) gag mRNA expression (left) and relative viability (right) of HIV-1 infected Jurkat-TAg cells transfected with non targeting siRNA (NC) or siRNAs targeting the HMOX-1 gene. Cells were infected 24hr post-transfection and assayed for mRNA expression (by qPCR) or viability (by MTT assay) 48hr post-infection. Data (mean±SEM; n=3 technical replicates) were normalized using the NC control and analyzed by unpaired t-test. P<0.05; **P<0.01.",
    "ncbi_link": "gag: 155030
HMOX-1: 3162"
  },
  {
    "caption": "(C) Heatmaps of the standardized expression of the GO iron ion import pathway genes in HIV-1 infected and mock infected samples over time. Expression levels were standardized [(mean gene expression - SD)/SD] for each gene in each time point. The TFRC (TfR1) gene, which was considered for further analysis, is highlighted.",
    "ncbi_link": "TfR1: 7037
TFRC: 7037"
  },
  {
    "caption": "(G) Percentage of GFP+ J-Lat cells (clones 9.2 and 15.4) left untreated or treated for 48hr with TPA (10μM), the iron donor FeNT (150μM) or a combination of the two. Data are expressed as mean±SEM of four technical replicates for each cell line and were analyzed by one-way ANOVA followed by Tukey´s post-test. *P<0.05; ***P<0.001; ****P<0.0001.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D) relative expression PML mRNA in HIV-1 infected vs mock infected CD4+ T-cells over time. Raw data were normalized using GAPDH or 18S (mRNA) as housekeeping control and expressed as Log2 fold change expression in infected vs mock infected cells. Data were analyzed by two-way ANOVA followed by Tukey´s post-test (mean±SEM of 3 and 4 biological replicates for PML mRNA",
    "ncbi_link": "18S: 
GAPDH: 2597
PML: 5371"
  },
  {
    "caption": "A549 were treated with Etoposide (Eto) for 2 hours to induce p53 pathway. Then cells have been challenged with Tm, Tg and BFA at the indicated concentrations for 16 hours. Luciferase experiments were performed after 24 hours of transfection. Graph shows the fold induction of p53 luciferase construct. Western blot experiments for phospho-p53, pan-p53, p21 and HSP90 were performed as control. n=3, biological replicates (mean ± SD; Differences were analyzed by Unpaired Student's t-test using Prism 9 (GraphPad), except when otherwise indicated. *p<0.05, ***p < 0.001.",
    "ncbi_link": "luciferase: 
p53: 7157"
  },
  {
    "caption": "A549 were transfected with control siRNA (siC) and AGR2-tergetd siRNA (siAGR2). After 24 hours, cells were transfected with p53-luciferase construct. Cells were then treated as in (C) and luciferase experiments were performed. n=4, biological replicates (mean ± SD. Differences were analyzed by Unpaired Student's t-test using Prism 9 (GraphPad), except when otherwise indicated.",
    "ncbi_link": "luciferase: 
AGR2: 10551
p53: 7157"
  },
  {
    "caption": "(F) Relative expression levels of cardiac hypertrophy markers (Nppa and Nppb) (n = 5). Bars represent mean ± S.E.M. (Student's t test; **p < 0.01, ****p < 0.0001).",
    "ncbi_link": "Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "(F) Relative expression levels of transcription factors involved in UPRmt and ISR (left) and Fgf21 (right) (n = 5). Bars represent mean ± S.E.M. (Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).",
    "ncbi_link": "Fgf21: 56636"
  },
  {
    "caption": "(A) Representative gel of the In organello translation analysis of heart mitochondria. De novo synthetized proteins are isolated after labeling with 35S-met (1 hour Pulse) or after cold chase (3h Chase). Positions of individual proteins are indicated on the left. Position of full-length proteins (Proficient) and low molecular weight polypeptides (Abortive) are indicated on the right. Note that in WT and ClpP KO low molecular weight polypeptides include ATP8/ND4L proteins.",
    "ncbi_link": "ClpP: 53895"
  },
  {
    "caption": "(D) Relative levels of the individual de novo synthesized OXPHOS subunits in DKO mitochondria normalized to the corresponding Dars2 KO polypeptide level.",
    "ncbi_link": "Dars2: 226539"
  },
  {
    "caption": "(A) Phosphorylated Myosin-II Regulatory Light Chain (p-MLC; purple) detected by antibody staining reveals high levels around the cortex of rounded mitotic cells in wild-type wing epithelial cells in the anterior (A) compartment, but not in Rho-kinase (Rok) RNAi expressing cells of the posterior (P) compartment (GFP-positive; green). Scale bar ~10µm. n>10 independent biological replicates.",
    "ncbi_link": "Rho-kinase: 43916
Rok: 43916"
  },
  {
    "caption": "(B) High-magnification view of single mitotic cell stained for p-MLC (purple) and E-cadherin (green), with metaphase plate chromosomes stained by DAPI (blue). Scale bar ~1µm. n>10 independent biological replicates. (C) High-magnification view of single UAS.Rok-RNAi expressing mitotic cell stained for p-MLC (purple) and E-cadherin (green), with metaphase plate chromosomes stained by DAPI (blue). Note loss of cortical p-MLC staining (purple). Scale bar ~1µm. n>10 independent biological replicates. ",
    "ncbi_link": "Rok: 43916"
  },
  {
    "caption": "(D) Expression of constitutively active Rho-kinase (UAS.Rok-CA) in the posterior compartment of the wing epithelium is sufficient to elevate p-MLC and reduce E-cadherin immunostaining. Zoom (right) shows high p-MLC and low E-cad in both a mitotic cell and its neighbours. Scale bar ~10µm. n>10 independent biological replicates.",
    "ncbi_link": "Rho-kinase: 43916
Rok: 43916"
  },
  {
    "caption": "(B) Phosphorylated Myosin-II Regulatory Light Chain (p-MLC; purple) detected by antibody staining reveals high levels around the cortex of rounded mitotic cells in wild-type wing epithelial cells, but not those expressing UAS.pbl-RNAi. Phospho-Histone H3 (pH3) staining (green) marks mitotic cell chromosomes. Quantification shown right (n > 10 independent samples per genotype; mean +/- 1 S.D. shown). Scale bar ~1µm.",
    "ncbi_link": "pbl: 38879"
  },
  {
    "caption": "(C) A stripe of expression of ptc.Gal4 UAS.pbl-RNAi in the wing disc leads to both enlarged cells and many basally extruded cells that undergo apoptosis, marked by pyknotic nuclei and loss of aPKC/Dlg staining. Scale bars ~20µm. n > 6 independent biological replicates.",
    "ncbi_link": "Gal4: 
pbl: 38879
ptc: 35851"
  },
  {
    "caption": "(B) A stripe of expression of ptc.Gal4 UAS.tum-RNAi in the wing disc leads to basally extruded cells that undergo apoptosis, marked by Dcp1 immunostaining, similar to UAS.pbl-RNAi. Quantification shown on the right (n > 10 independent samples per genotype; mean +/- 1 S.D. shown). Scale bars ~20µm.",
    "ncbi_link": "Gal4: 
pbl: 38879
ptc: 35851
tum: 36538"
  },
  {
    "caption": "(C) Phosphorylated Myosin-II Regulatory Light Chain (p-MLC; red) detected by antibody staining reveals high levels around the cortex of rounded mitotic cells in wild-type wing epithelial cells, but not those cells homozygous mutant for tum347, marked by expression of GFP in single-celled clones (MARCM system). pH3 staining (blue) marks mitotic cell chromosomes. Arrow indicates a GFP-positive single cell tum347 mutant clone. Quantification shown on the right (n > 3 independent samples per genotype; mean +/- 1 S.D. shown). Scale bars ~20µm.",
    "ncbi_link": "GFP: 
tum: 36538"
  },
  {
    "caption": "(A) Phosphorylated Myosin-II Regulatory Light Chain (p-MLC; purple) detected by antibody staining reveals high levels around the cortex of rounded mitotic cells (pH3, red) in wild-type wing discs, and aurA homozygous mutant wing discs, but not upon inhibition of both AurA and AurB by treatment with VX-680. Note increased numbers of mitotic cells in aurA homozygous mutant wing discs, due to delayed mitotic progression. Scale bars ~20µm (low mag.) and ~1µm (high mag.). n > 15 independent biological replicates.",
    "ncbi_link": "aurA: 41446"
  },
  {
    "caption": "(B) Live-imaging of MyoII-GFP reveals delayed mitosis in aurA homozygous mutant wing discs, while inhibition of both AurA and AurB by treatment with VX-680 leads to complete loss of mitotic rounding and MyoII-GFP membrane localisation. Asterisks indicate a single mitotic cell. Scale bars ~1µm. Quantification shown on the bottom right (n = 5 independent samples per genotype).",
    "ncbi_link": "aurA: 41446"
  },
  {
    "caption": "(C) Live-imaging of E-cad-GFP reveals delayed mitosis in aurA homozygous mutant wing discs, cytokinesis failure in UAS.aurB-RNAi expressing wing discs, and complete failure of mitotic rounding and E-cad-GFP downregulation upon inhibition of both AurA and AurB by treatment with VX-680. Asterisks indicate a single mitotic cell. Scale bars ~1µm. Quantification shown on the bottom right (n = 9 independent samples per genotype).",
    "ncbi_link": "aurA: 41446
aurB: 34504"
  },
  {
    "caption": "(A) Striped ptc.Gal4-driven expression of UAS.GFP in a control wing imaginal disc. Scale bars ~20µm. n > 6 independent biological replicates. (B) Striped ptc.Gal4-driven expression of UAS.GFP in an aurA homozygous mutant wing imaginal disc leads to increased numbers of pH3 positive mitotic cells. n > 7 independent biological replicates. (C) Striped ptc.Gal4-driven expression of UAS.GFP and UAS.aurB-RNAi in a control wing imaginal disc leads to enlarged cells with large nuclei (marked by DAPI; white arrowhead). n > 6 independent biological replicates. (D) Striped ptc.Gal4-driven expression of UAS.GFP and UAS.aurB -RNAi in an aurA homozygous mutant wing imaginal disc leads to extrusion and apoptosis of cells (marked by Dcp1 and pyknotic nuclei). n > 8 independent biological replicates. (E) Striped ptc.Gal4-driven expression of UAS.GFP and UAS.pbl-RNAi in the wing imaginal disc leads to extrusion and apoptosis of cells (marked by Dcp1 and pyknotic nuclei). n > 8 independent biological replicates. (F) ptc.Gal4-driven expression of UAS.aurB-RNAi in an aurA homozygous mutant endoreplicating salivary gland has no phenotypic consequence. n > 6 independent biological replicates. ",
    "ncbi_link": "Gal4: 
GFP: 
aurA: 41446
aurB: 34504
pbl: 38879
ptc: 35851"
  },
  {
    "caption": "(G) MARCM clones (GFP-positive) expressing UAS.aurB-RNAi in an aurA homozygous mutant cells result in single cell clones (i.e.: no cell division), while individual loss of AurA or AurB allows some cell proliferation. Quantification shown on the right (n > 7 independent samples per genotype; Mean +/- 1 S.D. shown). Scale bar ~20µm.",
    "ncbi_link": "aurA: 41446
AurA: 41446
aurB: 34504
AurB: 34504"
  },
  {
    "caption": "Analysis of relative transcript levels of CD11b+CD45int FACS-sorted microglia compared with whole brain tissue by qPCR. Gene expression levels of microglia (Olfml3, Fcrls, Tmem119, Siglech, Gpr34, P2ry12), astrocyte (Gfap, Gjb6, Ntsr2, Aldh1l1), oligodendrocyte (Mobp, Mog, Cldn1), and neuron (Tubb3, Vglut1, NeuN) markers. Bars represent mean (n=4; pool of 1 female and 1 male per biological replicate) of relative expression (Gapdh as housekeeping gene) ± SEM (*p < 0.05; **p < 0.01 by two-tailed Student's test). N.D. not detected.",
    "ncbi_link": "Gapdh: 
Aldh1l1: 107747
Cldn1: 12737
Fcrls: 80891
Gfap: 14580
Gjb6: 14623
Gpr34: 23890
Mobp: 17433
Mog: 17441
Ntsr2: 18217
Olfml3: 99543
P2ry12: 70839
NeuN: 52897
Siglech: 233274
Vglut1: 72961
Tmem119: 231633
Tubb3: 22152"
  },
  {
    "caption": "Three-four months old BL/6 mice were treated with an acute dose of LPS (4 µg/g body) or vehicle (saline). Microglia (pool of 2 mice per group per replicate; 1 female and 1 male) were FACS-sorted 24 hours later. Gene expression levels of microglia homeostatic (Olfml3, Fcrls, Tmem119, Siglech, Gpr34, P2ry12, Mef2c), phagocytic (Tyrobp, Trem2), and inflammatory (Il1β, Tnf, Ccl2, Mrc1, Arg1) markers were analyzed by qPCR. Bars represent mean of relative expression (% of saline; Gapdh as housekeeping gene) ± SEM (*p < 0.05; **p < 0.01 by two-tailed Student's test; n=4).",
    "ncbi_link": "Gapdh: 
Arg1: 11846
Ccl2: 20296
Fcrls: 80891
Gpr34: 23890
Il1β: 16176
Mef2c: 17260
Mrc1: 17533
Olfml3: 99543
P2ry12: 70839
Siglech: 233274
Tmem119: 231633
Tnf: 21926
Trem2: 83433
Tyrobp: 22177"
  },
  {
    "caption": "Three-four months old BL/6 mice were treated with an acute dose of LPS (4 µg/g body) or vehicle (saline). Microglia (pool of 2 mice per group per replicate; 1 female and 1 male) were FACS-sorted 24 hours later. Gene expression levels of the monocytic markers Ly6c1 and Ccr2 in purified microglia (n=4) and isolated bone marrow monocytes (n=2) by qPCR. Bars represent mean of relative expression (Gapdh as housekeeping gene) ± SEM (**p < 0.01 by two-tailed Student's test).",
    "ncbi_link": "Gapdh: 
Ccr2: 12772
Ly6c1: 17067"
  },
  {
    "caption": "Primary adult microglia were cultivated in the presence of TGF-β (50 μg/ml) and M-CSF (10 ng/ml), while neonatal cells were stimulated for 24 hours with TGF-β (50 μg/ml) followed by 6 hours stimulation with LPS (1 ng/mL) or left untreated. Expression levels of microglia homeostatic (Olfml3, Tmem119, Gpr34) and inflammatory (Il1β, Tnf, Ccl2) genes were analysed by qPCR. Bars represent mean of relative expression (Gapdh as housekeeping gene) ± SEM (**p < 0.01 by two-tailed Student's test; n=3).",
    "ncbi_link": "Gapdh: 
Ccl2: 20296
Gpr34: 23890
Il1β: 16176
Olfml3: 99543
Tmem119: 231633
Tnf: 21926"
  },
  {
    "caption": "Expression of specific homeostatic (Tmem119, P2ry12, Siglech) and inflammatory (Ccl2, Gpr84) genes overlaid on the 2D-tSNE space. Bars represent log2 (Count+1).",
    "ncbi_link": "Ccl2: 20296
Gpr84: 80910
P2ry12: 70839
Siglech: 233274
Tmem119: 231633"
  },
  {
    "caption": "Heatmap showing examples of specific genes mainly up-regulated in \"main LPS\" (Manf) or \"subset LPS\" (Ash1l) and down-regulated in \"main LPS\" (Mef2c) or \"subset LPS\" (Lamp1) overlaid on the 2D-tSNE space. Bars represent log2 (Count+1).",
    "ncbi_link": "Ash1l: 192195
Lamp1: 16783
Manf: 74840
Mef2c: 17260"
  },
  {
    "caption": "Pseudotime dynamics of inflammatory (Ccl12, Ccl2, Gpr84) and homeostatic (Mef2c, P2ry12, Siglech) genes in dependence on inferred cell states.",
    "ncbi_link": "Ccl12: 20293
Ccl2: 20296
Gpr84: 80910
Mef2c: 17260
P2ry12: 70839
Siglech: 233274"
  },
  {
    "caption": "C-E KRAS and TP53 alterations in the cancer genome atlas (TCGA) pan-cancer MPM dataset (n = 86 patients). Shown are clinical and molecular data plot with alteration frequencies (C) and patients reclassified as KRAS- or TP53-altered (asterisks), copy number variation data summary (D), and segments of the KRAS and TP53 loci (E).",
    "ncbi_link": "KRAS: 3845
TP53: 7157"
  },
  {
    "caption": "Molecular and clinical features of the cancer genome atlas (TCGA) pan-cancer MPM patients (n = 87) stratified by the presence of KRAS standalone (n = 10) and combined KRAS/TP53 (n = 7) alterations. Shown are unsupervised hierarchical clustering of n = 86 patients (gene expression data were not available for one patient) by 40 genes significantly overexpressed in KRAS/TP53-altered over KRAS-altered over KRAS/TP53-normal patients (A) and data summaries of mononucleotide change signatures (B), of indices of genomic instability and mutation burden (C), of clinical features",
    "ncbi_link": "KRAS: 3845
TP53: 7157"
  },
  {
    "caption": "Molecular and clinical features of the cancer genome atlas (TCGA) pan-cancer MPM patients (n = 87) stratified by the presence of KRAS standalone (n = 10) and combined KRAS/TP53 (n = 7) alterations. Shown are unsupervised hierarchical clustering of n = 86 patients (gene expression data were not available for one patient) by 40 genes significantly overexpressed in KRAS/TP53-altered over KRAS-altered over KRAS/TP53-normal patients overall survival (F).",
    "ncbi_link": "KRAS: 3845
TP53: 7157"
  },
  {
    "caption": "H Data summary of mutant allelic frequency of KRAS compared with NF2 and BAP1 in all mutated samples from (A-G).",
    "ncbi_link": "BAP1: 8314
KRAS: 3845
NF2: 4771"
  },
  {
    "caption": "Pleural fluid cell pellets and supernatants from 10 patients (called CRCINA #) with pleural effusion and pleural tumor samples from 17 patients (called TR#) with MPM were subjected to digital droplet polymerase chain reaction (ddPCR) for the detection of mutant (MUT) copies of KRAS codon 12/13 (KRASG12/13) and KRAS codon 61 (KRASQ61), as well as copies of TP53 and TERT. Diagnoses were lung adenocarcinoma (LUAD; n = 4) and MPM (n = 23). The assays were designed for detection of down to 1:20000 copies using EKVX (KRASWTTP53G610T), A549 (KRASG12STP53WT), NCI-H460 (KRASQ61HTP53WT), NCI-H3122 (KRASWTTP53E285V), and NCI-H3255 (KRASWTTP53G560-1A) human LUAD cells as controls. Shown are individual patient (KRAS plot) and individual sample (TP53 plot) allelic frequencies with color code and limits of normal TP53 allelic frequency as vertical dashed lines in the TP53 plot (A) Any number of KRAS-mutant droplets detected in any sample (KRAS plot in A) and any patient that failed to achieve normal TP53 ploidy by any sample (TP53 plot in A) was deemed altered.",
    "ncbi_link": "KRAS: 3845
TERT: 7015
TP53: 7157"
  },
  {
    "caption": "F Representative May-Gruenwald-Giemsa-stained pleural fluid cytocentrifugal specimen from a KRASG12D;Trp53f/f mouse showing macrophages (MΦ, black arrow), lymphocytes (LΦ, purple arrow), and neutrophils (NΦ, green arrow) and summary of cellular and biochemical features of effusions of KRASG12D;Trp53f/f mice (n = 10).",
    "ncbi_link": "KRAS: 16653
Trp53f: 22059"
  },
  {
    "caption": "Wild-type (Wt), KRASG12D, and Trp53f/f mice were intercrossed, and all possible offspring genotypes received 5 x 108 PFU intrapleural or intratracheal Ad-Cre and were sacrificed when moribund. In parallel, C57BL/6 mice received ten consecutive weekly intraperitoneal injections of 1 g/Kg urethane and were sacrificed after six months. Data summary (heatmap) and representative images of immunoreactivity of tissue sections of pleural and pulmonary tissues and tumors from these mice for different markers of human malignant pleural mesothelioma (MPM) and lung adenocarcinoma (LUAD). n = 10 mice/group were analyzed for each marker. Brown color indicates immunoreactivity and blue color nuclear hematoxylin counterstaining. Note the ubiquitous strong expression of Wilms' tumor 1 (WT1), patchy moderate expression of vimentin (VIM), ubiquitous moderate expression of mesothelin (MSLN), ubiquitous strong expression of calretinin (CALB2), podoplanin (PDPN), and osteopontin (SPP1), patchy moderate expression of cytokeratin 5/6 (CK5/6), and the absence of expression of surfactant protein C (SFTPC) in murine KRAS-driven mesotheliomas. Note also the ubiquitous strong expression of WT1, the patchy moderate expression of VIM, the ubiquitous low-level expression of MSLN, the ubiquitous strong expression of CALB2 and SPP1, the ubiquitous low-level expression of PDPN, the variable moderate expression of CK5/6, and the ubiquitous moderate expression of SFTPC in murine KRASG12D-driven and urethane-induced LUAD.",
    "ncbi_link": "Cre: 2777477
KRAS: 16653
Trp53: 22059"
  },
  {
    "caption": "E, F RT-PCR (E) and qPCR (F) of KPM cells and parental tumors show Trp53f/f allele deletion (Δ) and Bap1 and Cdkn2a overexpression compared with PMC.",
    "ncbi_link": "Bap1: 104416
Cdkn2a: 12578
Trp53: 22059"
  },
  {
    "caption": "I-K) Representaitve pictures showing that adult nerfin-1 clonal growth was significantly reduced on -his diet compared to CDD (measured at day 0, and day 9) quantified in (K) (n= 27, 110, 136). Scale bar = 75μm. ***p<0.001 L-N) Representaitve pictures showing that larval nerfin-1 clonal growth was significantly reduced on 25% his diet compared to CDD (after 6 days), quantified in (N) (n=53,36). Scale bar = 50 μm. ",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "O-Q) Representaitve pictures showing that adult pros clonal growth was not significantly altered on -his diet compared to CDD (after 7 days), quantified in (Q) (n = 12, 23,16). Scale bar = 75μm. R-T) Representaitve pictures showing that larval pros clonal growth was not significantly altered by dietary histidine reduction (25% his) compared to CDD (after 6 days), quantified in (T) (n=19,13). Scale bar = 50 μm. ",
    "ncbi_link": "pros: 41363"
  },
  {
    "caption": "U-W) Representative pictures showing that the growth of larval type II lineages overexpressing NACT was significantly reduced dietary histidine reduction (25% his) compared to CDD, quantified in (W) (n=27,19). Scale bar = 100 μm.",
    "ncbi_link": "NACT: 31293"
  },
  {
    "caption": "C) Dietary supplementation of 3-methyl-L-his for 4 days significantly increased adult nerfin-1 clonal growth, and rescued nerfin-1 growth inhibition due to his dietary withdrawal (n =18,14, 7,9).",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "D) Dietary supplementation of histamine does not significantly increase adult nerfin-1 clone size, but can rescue nerfin-1 clonal growth inhibition due to his dietary withdrawal (n =42,14,23,25).",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "E) Larval nerfin-1 clonal growth is significantly decreased upon overexpression of HDC RNAi (n=23,36).",
    "ncbi_link": "HDC: 36076
nerfin-1: 44786"
  },
  {
    "caption": "G) Hdc inhibition significantly reduced the percentage of Dpn+ NBs (n=16,17), and significantly increased the percentage of Elav+ neurons per clone (n=16,17).",
    "ncbi_link": "Hdc: 36076"
  },
  {
    "caption": "H) HdcRi overexpression reduced cellular growth of nerfin-1 NBs (n=17,19) and neurons (n=36,19) measured as the ratio of nucleolus/nuclear volume.",
    "ncbi_link": "Hdc: 36076
nerfin-1: 44786"
  },
  {
    "caption": "A-E) Representative images of nerfin-1 clones in the adult VNC after 6 days of feeding on CDD or -his diet, scale bar = 100μm. Histidine dietary withdrawal resulted in clones significantly altering the amount of cell death per clone quantified in (C) (n = 6, 7).",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "F-G) Larval nerfin-1 clones consisted of significantly greater proportion of differentiated neurons (n=10,7) and significantly reduced proportion of NBs per clone upon his dietary depletion (25% his, n=9,11).",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "Representative images of adult nerfin-1 (I-J', green ) and pros clones (K-L', green), scale bar = 5μm. In nerfin-1 clones, the size of the NBs (Ase+, blue) was significantly reduced upon 6 days of histidine dietary withdrawal, quantified in (H) (n=33,20). In pros clones, the size of the NBs (Ase+ blue), and cellular growth measured as the ratio of nucleolus (Fib, white)/nuclear (Ase, blue) volume was not significantly altered upon 6 days of histidine dietary withdrawal, quantified in (H) (n=9,8)",
    "ncbi_link": "nerfin-1: 44786
pros: 41363"
  },
  {
    "caption": "Cellular growth measured as the ratio of nucleolus /nuclear volume was significantly reduced in larval nerfin-1 NBs after 6 days his dietary reduction (25% his compared to CDD, n=14,6) quantified in (N).",
    "ncbi_link": "nerfin-1: 44786"
  },
  {
    "caption": "In pros clones, the size of the NBs (Ase+ blue), and cellular growth measured as the ratio of nucleolus (Fib, white)/nuclear (Ase, blue) volume was not significantly altered upon 6 days of histidine dietary withdrawal, quantified in (O) (n=9,7).",
    "ncbi_link": "pros: 41363"
  },
  {
    "caption": "Panel (P) shows that the larval nerfin-1 neuron to NB reversion requires 15-fold increase in cellular volume (n=10) and pros GMC to NB reversion requires approximately 3.5-fold increase in cellular volume (n=31).",
    "ncbi_link": "nerfin-1: 44786
pros: 41363"
  },
  {
    "caption": "A-D) Representative pictures showing that pros NBs and GMCs are smaller than wildtype (NBs and GMCs are distinguished at telophase, as a doublet of unequal size), quantified in C (n=25,31,21,16). pros NBs exhibit similar nucleolus /nuclear ratio (white arrows, nucleolus marked by Fib) compared to wild type and pros;TorDN NBs, quantified in D (n=10,18,15).",
    "ncbi_link": "pros: 41363
Tor: 47396"
  },
  {
    "caption": "E-F) Representative pictures showing pros clones (green) generated in myc hypomorphic background did not significantly alter pros nucleolus/nuclear ratio (E-F)",
    "ncbi_link": "myc: 31310
pros: 41363"
  },
  {
    "caption": "pros clones (green) generated in myc hypomorphic background did not significantly alter pros nucleolus/nuclear ratio (E-F), nucleolus labelled with Fib (red) [quantified in G (n=44,43)], clone size [quantified in H (n=41,34)], or the proportion of Dpn+ NBs and Elav+ neurons per clone [quantified in I (n=15,15,15,15)].",
    "ncbi_link": "myc: 31310
pros: 41363"
  },
  {
    "caption": "J-K) Representative pictures showing that nerfin-1 clones (green) generated in myc hypomorphic background (J-K)",
    "ncbi_link": "myc: 31310
nerfin-1: 44786"
  },
  {
    "caption": "nerfin-1 clones (green) generated in myc hypomorphic background (J-K) exhibited significantly reduced nucleolus/nuclear ratio, [nucleolus labelled with Fib (red)] and reduced clone size, quantified in L (n=34,27) and M (n= 106,75), and displayed an increased proportion of differentiated Elav+ neurons, and reduced proportion of Dpn+ NBs per clone, quantified in N (n=20,20,20,20). scale bar =10μm",
    "ncbi_link": "myc: 31310
nerfin-1: 44786"
  },
  {
    "caption": "O) Reducing Myc dosage with the hypomorphic Myc allele, mycP0, abolished the increase in nerfin-1 clone size mediated by 2x histidine dietary intake, 2x his (n=41,18,10,57).",
    "ncbi_link": "myc: 31310
Myc: 31310
nerfin-1: 44786"
  },
  {
    "caption": "P) Overexpression of myc restored the growth of nerfin-1 clones inhibited by histidine dietary reduction, 25% his (n=51,36,39,29).",
    "ncbi_link": "myc: 31310
nerfin-1: 44786"
  },
  {
    "caption": "Q, R) pros (Q) and nerfin-1 (R) clones are reduced upon Tor inhibition (n=22,63) compared to control (n=51,65), but their growth differentially depend on amino acid transporter Slif ( n=12,32) and downstream growth regulators eIF4E (n= 21,47) and S6K (n=39,37).",
    "ncbi_link": "eIF4E: 45525
nerfin-1: 44786
pros: 41363
S6K: 38654
Slif: 40510
Tor: 47396"
  },
  {
    "caption": "(A) The mRNA level of ATG-5 was detected by real time PCR after treatment with siRNAs. GAPDH was used as internal controls.",
    "ncbi_link": "ATG-5: 
GAPDH: 2597"
  },
  {
    "caption": "C. MDCK cells stably expressing human CD63 were cultured sEVs were isolated from the pre-cleared medium by direct immunoaffinity capture using anti-CD63 antibody.",
    "ncbi_link": "CD63: 967"
  },
  {
    "caption": "F. MDCK cells stably expressing human CD63 were cultured sEVs were isolated from the pre-cleared medium by direct immunoaffinity capture using anti-CD63 antibody.",
    "ncbi_link": "CD63: 967"
  },
  {
    "caption": "B. Splicing of XBP1 mRNA was assessed by RT-PCR. Products from unspliced (XBP1u) and spliced (XBP1s) transcripts were resolved on a nondenaturing polyacrylamide gel and stained with SYBR green.",
    "ncbi_link": "XBP1: 7494"
  },
  {
    "caption": "C. Relative mRNA expression in proximal hind limb muscle (mean +/− SEM). Mice evaluated were littermate WT (n = 6), AR113Q (n = 6), castrated WT (C-WT, n = 6) and castrated AR113Q males (C-AR113Q, n = 5) on a mixed C57BL/6J-129 genetic background. *p<0.05 by ANOVA.",
    "ncbi_link": "AR: 11835"
  },
  {
    "caption": "E. Relative mRNA expression in proximal hind limb muscle of AR21Q (n = 5) and AR113Q (n = 3) males backcrossed to C57BL/6J. ** p<0.01, ***p<0.001 by Student's t test. F. Relative mRNA expression in spinal cord of AR21Q (n = 5) and AR113Q (n = 3) males (mean +/− SEM). n. s. = not significant by Student's t test.",
    "ncbi_link": "AR: 11835"
  },
  {
    "caption": "A. Muscle fiber size (100 fibers/mouse) was quantified from proximal hind limb muscle of AR113Q (black) or AR113Q, CHOP −/− mice (white) at 12 wks. Left panel shows fiber size distribution, middle panel shows cumulative percent of fibers as a function of fiber area, and right panel shows relative fiber cross sectional area (mean +/− SEM). Left, middle panels, p<0.0001 by Mann-Whitney test. Right panel, p<0.001 by Student's t test.",
    "ncbi_link": "AR: 11835
CHOP: 13198"
  },
  {
    "caption": "C. Distribution of proximal hind limbmuscle fiber size from wt (black) and CHOP −/− (white) mice at 12 wks. Difference not significant by Mann-Whitney test.",
    "ncbi_link": "CHOP: 13198"
  },
  {
    "caption": "A. Relative expression of MurRF1 and MAFbx mRNAs in proximal hind limbmuscle of 12 wk mice (n = 5-6/genotype). *p<0.05 by ANOVA, n. s. = not significant.",
    "ncbi_link": "MAFbx: 67731
MurRF1: 433766"
  },
  {
    "caption": "Denervated gastrocnemius muscles or contralateral intact controls were harvested at the indicated times following unilateral sciatic nerve transection in 6 wk male mice. A. Western blot shows enhanced eIF2 alpha phosphorylation (top) and RT-PCR demonstrates increased XBP1 mRNA splicing (bottom) in denervated muscle. Right panels show relative quantification of signal intensity. *p<0.05 by Student's t test.",
    "ncbi_link": "XBP1: 22433"
  },
  {
    "caption": ". B. Relative expression of BiP, ATF4 and CHOP mRNA (n = 3). *p<0.05 by Student's t test.",
    "ncbi_link": "ATF4: 11911
CHOP: 13198
BiP: 14828"
  },
  {
    "caption": "C. Following surgical denervation of wild type or CHOP−/− mice, LC3 and p62 expression was assessed by western blot. Right panels show quantification of signal relative to GAPDH. ***p<0.001 by ANOVA, n. s. = not significant.",
    "ncbi_link": "CHOP: 13198"
  },
  {
    "caption": "D. Muscle fiber size (100 fibers/mouse) was quantified from wild type (black, n = 5), CHOP −/− (white, n = 3) and Beclin-1 +/− (grey, n = 3) mice 7 days post sciatic nerve transection. Shown is relative fiber cross sectional area (mean +/− SEM). ***p<0.001 by ANOVA.",
    "ncbi_link": "Beclin-1: 56208
CHOP: 13198"
  },
  {
    "caption": "E. Muscle fiber size (100 fibers/mouse) was quantified from CHOP −/− (black, n = 6) or CHOP −/−, Beclin-1 +/− mice (white, n = 6) 7 days post sciatic nerve transection. Left panel shows fiber size distribution, middle panel shows cumulative percent of fibers as a function of fiber area, and right panel shows relative fiber cross sectional area (mean +/− SEM). Left, middle panels, p<0.0001 by Mann-Whitney test. Right panel, p<0.001 by Student's t test.",
    "ncbi_link": "Beclin-1: 56208
CHOP: 13198"
  },
  {
    "caption": "A. Muscle fiber size (100 fibers/mouse) was quantified from proximal hind limbmuscle of AR113Q (red, n = 6) or AR113Q, Beclin-1 +/− (blue, n = 6) mice at 16 wks. Left panel shows fiber size distribution, and right panel shows relative fiber cross sectional area (mean +/− SEM). Left panel, p<0.0001 by Mann-Whitney test. Right panel, p<0.0001 by Student's t test.",
    "ncbi_link": "AR: 11835
Beclin-1: 56208"
  },
  {
    "caption": "A. Left panel, Kaplan-Meyer survival curve of AR113Q males (red line, n = 12) and AR113Q, Beclin-1 +/− males (blue line, n = 15). *p<0.05 by log-rank analysis. Right panel, mean survival +/− SEM. *p<0.05 by Student's t-test.",
    "ncbi_link": "AR: 11835
Beclin-1: 56208"
  },
  {
    "caption": "B, C. Body weight (panel B) and grip strength (panel C) at different ages for wild type (wt, green line, n = 7), Beclin-1 +/− (yellow line n = 9), AR113Q (red line, n = 12), and AR113Q, Beclin-1 +/− (blue line, n = 15) male mice.",
    "ncbi_link": "AR: 11835
Beclin-1: 56208"
  },
  {
    "caption": "B, C. Body weight (panel B) and grip strength (panel C) at different ages for wild type (wt, green line, n = 7), Beclin-1 +/− (yellow line n = 9), AR113Q (red line, n = 12), and AR113Q, Beclin-1 +/− (blue line, n = 15) male mice.",
    "ncbi_link": "AR: 11835
Beclin-1: 56208"
  },
  {
    "caption": "A. Western blot analysis of supernatants and whole cell lysates collected from WT and IQGAP1 KO YAMC cells with and without LPS stimulation for 4 hours or LPS plus ATP (4 hours plus 30 minutes) treatment as indicated.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "B. Nanoparticle tracking analysis of supernatant of WT and IQGAP1 KO YAMC cells treated with LPS plus ATP. **, P<0.01 by unpaired two-tailed t test (n=3 biological repeats in one experiments).",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "D. Western blot analysis of enriched extracellular vesicles from supernatants WT and IQGAP1 KO YAMC cells.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "F. Flow cytometry analysis for CD63+ exosomes from supernatants of LPS plus ATP treated WT and IQGAP1 KO supernatants. Quantification was done by mean fluorescence intensity. **, P<0.01 by unpaired two-tailed t test (n=4).",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "B. Co-immunoprecipitation of GSDMD with full-length and deletion mutants of IQGAP1 tested in HEK293 cells.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "C. Co-immunoprecipitation of GSDMD cleavage mutant D276A with IQGAP1 overexpressed in HEK293 cells.",
    "ncbi_link": "GSDMD: 69146
IQGAP1: 29875"
  },
  {
    "caption": "D. Co-immunoprecipitation of GSDMD with IQGAP1 in WT and cleavage mutant (D276A) restored GSDMD KO YAMC cells. Cells were treated as indicated.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "E. Co-immunoprecipitation of C-terminal GSDMD (CT) with IQGAP1 overexpressed in HEK293 cells.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "A. Imaging analysis for co-localization of CD63 with IQGAP1 in IQGAP1 (FL) and IQ domain truncation (ΔIQ) restored YAMC cell. Cells were treated with LPS plus ATP. The IQGAP1-CD63 co-localization dots (shown by yellow) were counted, and Pearson's correlation coefficient was calculated for the quantification of co-localization.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "B. Imaging analysis for co-localization of CD63 with GSDMD in IQGAP1 full length (FL) and IQ domain truncation restored YAMC cell (ΔIQ) after LPS plus ATP treatment. The GSDMD-CD63 co-localized dots were counted and Pearson's correlation coefficient was calculated for quantification.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "C. Proximity ligation assay for IQGAP1 and GSDMD in IQGAP1 FL restored cells and ΔIQ restored cells.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "D. Western blots analysis for supernatants collected from IQGAP1 KO YAMC cells, IQGAP1 full length and IQ domain truncation restored IQGAP1 KO YAMC cells. Cells were treated as indicated and the supernatants were subjected to IP with anti-IL-1β. E. Western blots analysis for whole cell lysate collected from panel D.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "A. Imaging analysis for early endosome (shown by marker EEA1) change in WT and IQGAP1 KO YAMC cells upon indicated treatments. Quantification was done by counting the EEA1 puncta from each cell. Five field views of cells' puncta were counted. Three independent experiments were repeated",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "B. Co-localization of CD63 and IQGAP1 in YAMC and GSDMD KO YAMC cells. Yellow dots indicated the co-localization signal.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "C. Co-localization of CD63 and GSDMD in YAMC and IQGAP1 KO YAMC cells.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "E. Co-localization of CD63 and pro-IL-1β in YAMC and IQGAP1 KO YAMC cells.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "F. Western blot analysis of extracellular vesicle secretion from WT and TSG101 knockdown cells upon indicated treatments. Secreted proteins were pulled down by IL-1β in the supernatant and the indicated proteins were probed for.",
    "ncbi_link": "TSG101: 22088"
  },
  {
    "caption": "G. Total particle count and size distribution for exosomes collected from WT and TSG101 knockdown cell supernatants with indicated treatment.",
    "ncbi_link": "TSG101: 22088"
  },
  {
    "caption": "H. Western blot analysis for interaction of TSG101 with IQGAP1 in WT and GSDMD KO cells by pulling down IQGAP1 under indicated treatments.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "I. Co-immunoprecipitation of GSDMD with TSG101 in WT and IQGAP1 KO cells by pulling down TSG101 under indicated treatments.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "A. Total particle count and size distribution of exosomes secreted in the supernatant from IQGAP1 KO (IQ1 KO), IQGAP1 full length restored (FL) and GRD domain truncation restored (ΔGRD) YAMC cells upon LPS or LPS plus ATP treatment.",
    "ncbi_link": "IQ1: 29875
IQGAP1: 29875"
  },
  {
    "caption": "B. PLA assay for IQGAP1 and CDC42 interaction in IQGAP1 FL restored cell and ΔGRD restored cell. The green dots showed the interaction of IQGAP1 and CDC42.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "C. Colocalization of CD63 with IQGAP1-CDC42 complex (shown by PLA signal) in WT and GSDMD KO cells under LPS treatment. Quantification was performed by counting PLA green dots.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "D. Co-immunoprecipitation analysis of endogenous IQGAP1 with CDC42 in wild-type and GSDMD KO cells upon LPS or LPS plus ATP treatment.",
    "ncbi_link": "GSDMD: 69146"
  },
  {
    "caption": "F. Co-immunoprecipitation analysis of endogenous GSDMD with CDC42 in wild-type and IQGAP1 KO cells upon LPS or LPS plus ATP treatment.",
    "ncbi_link": "IQGAP1: 29875"
  },
  {
    "caption": "B. Total particle count and size distribution for exosomes collected from colon explant of DSS treated IQGAP1 or GSDMD knockout mice and their respective controls.",
    "ncbi_link": "GSDMD: 69146
IQGAP1: 29875"
  },
  {
    "caption": "C. Western blot analysis for supernatant collected from colon explants of DSS-treated wild-type (WT), Gsdmd-/-(GSDMD KO) and Iqgap1-/- (IQGAP1 KO) mice. Supernatant was first pulled down by IL-1β antibody and samples were subjected to Western blot analysis. The indicated proteins were probed.",
    "ncbi_link": "Gsdmd: 69146
Iqgap1: 29875"
  },
  {
    "caption": "D. Immunofluorescent staining with anti-GTP-CDC42 in DSS treated colons from Gsdmd+/+ (WT) and Gsdmd-/-(GSDMD KO), IQGAP1+/+ and IQGAP1-/- mice.",
    "ncbi_link": "Gsdmd: 69146
GSDMD: 69146
IQGAP1: 29875"
  },
  {
    "caption": "Analysis of BrdU incorporation by BrdU-IP-chip 45 minutes after release into S phase in cells treated with 0.1% MMS as described in (A). A representative region on chromosome VII is shown. The position of replication origins is indicated above the map. Asterisks: late origins firing in mrc1∆ cells.",
    "ncbi_link": "mrc1: 850297"
  },
  {
    "caption": "Quantification of the BrdU incorporation (signal log ratio) at 384 early and late replication origins in wild type, rad9∆ and mrc1∆ strains exposed to 0.1 or 0.033% MMS. Red lines indicate median values. Median replication times (Trep) are indicated for bins of 96 origins.",
    "ncbi_link": "mrc1: 850297
rad9: 851803"
  },
  {
    "caption": "Wild type, mrc1∆ and rad9∆ cells were released into S phase in the presence of BrdU and 0.033% MMS, as described in Fig. 1A. DNA combing analysis was performed for samples collected 45 and 60 min after release into S phase. Representative DNA fibers are shown. Red: DNA, green: BrdU. Bar is 20 kb.",
    "ncbi_link": "mrc1: 850297
rad9: 851803"
  },
  {
    "caption": "Wild type, mrc1∆ and rad9∆ cells were synchronized in G1 with α-factor prior to release with pronase in the presence of 0.033% MMS. Cells were collected at the indicated times and Rad53 phosphorylation was monitored by western blot The asterisk indicates a non-specific band detected by the anti-Rad53 antibody.",
    "ncbi_link": "mrc1: 850297
rad9: 851803"
  },
  {
    "caption": "Wild type, mrc1∆ and rad9∆ cells were synchronized in G1 with α-factor prior to release with pronase in the presence of 0.033% MMS. Cells were collected at the indicated times and Rad53 phosphorylation was monitored with an in situ phosphorylation assay - ISA (F).",
    "ncbi_link": "mrc1: 850297
rad9: 851803"
  },
  {
    "caption": "2D gel analysis of initiation and elongation in wild type and rad9∆ cells at the early origin ARS719 (probe 1) and at a locus 7 kb away of the origin (probe 2). Time in Zeocin after the HU wash is indicated. Arrows point to Y arcs (fork signals) with the strongest intensity.",
    "ncbi_link": "rad9: 851803"
  },
  {
    "caption": "2D gel analysis of fork progression in wild type and rad9∆ cells through a 70-kb region of chromosome VI for which all active origins downstream of ARS607 have been deleted. The position of probes and the time after release from HU are indicated. Arrows point to Y arcs (fork signals) with the strongest intensity.",
    "ncbi_link": "rad9: 851803"
  },
  {
    "caption": "Distribution of BrdU tracks length in wild type, mrc1∆ and mrc1AQ cells. DNA fibers are fully labeled in the case of rad9∆ cells. Median values are indicated in red and correspond to the analysis of at least 150 tracks from two biological replicates. ns: non-significant Mann-Whitney rank sum test.",
    "ncbi_link": "mrc1: 850297
rad9: 851803"
  },
  {
    "caption": "Analysis of chromosome mobility by Pulse Field Gel Electrophoresis (PFGE) after staining of DNA with ethidium bromide. In G1, the chromosomes are linear and are sorted according to their length. Upon entry into S phase (30 min), they cannot enter the gel due to the presence of replication intermediates. Quantitation of chromosomes re-entering the gel shows completion of DNA replication in 40% of rad9∆, rad53-11 and rad9∆ rad53-11 mutants, but not in wild type cells and mrc1 mutants as determined for a representative experiment. Error bars indicate SD between the signal intensity determined for the three larger chromosomes (arrowheads).",
    "ncbi_link": "mrc1: 850297
rad53: 855950
rad9: 851803"
  },
  {
    "caption": "Length distribution of BrdU tracks measured at that time for wild type, rad9∆, rad53-11 and rad53-11 rad9∆ cells. Median lengths are indicated in red. For each sample, at least 200 tracks were measured from two biological replicates.",
    "ncbi_link": "rad53: 855950
rad9: 851803"
  },
  {
    "caption": "B Gene expression analysis by RT-qPCR for naive (KLF17, TFCP2L1, and NANOG) and trophoblast  (GATA3, GATA2, KRT7, ELF5, TP63, and TFAP2A) marker genes in naive-iPSCs  and TSC  cells derived from two different naive-iPSC  lines (HPD06  and H9).",
    "ncbi_link": "ELF5: 2001
GATA2: 2624
GATA3: 2625
KLF17: 128209
KRT7: 3855
NANOG: 79923
TFAP2A: 7020
TFCP2L1: 29842
TP63: 8626"
  },
  {
    "caption": "F Barplots showing the absolute expression as log(CPM+1) of ADAP2, HAVCR1, SLC28A3, ARID5B, and GATA2  in the reported conditions. Data information: (F) Bars indicate the mean ± SEM of at least n=5 biological replicates from at least 2 independent studies shown with different symbols. ***P < 0.001, ns no significance (Student's t-test).",
    "ncbi_link": "ADAP2: 55803
ARID5B: 84159
GATA2: 2624
HAVCR1: 26762
SLC28A3: 64078"
  },
  {
    "caption": "D Barplots showing the absolute expression  as log(CPM+1) of general pluripotency (OCT4  and NANOG), naive (SUSD2), and TSC-specific genes (GATA2, GATA3, KRT7, and ADAP2) in the reported conditions highlighted in different colours. Data information: (D) Dots indicate biological replicates and bars indicate the mean ± SEM of n=3 biological replicates.",
    "ncbi_link": "ADAP2: 55803
GATA2: 2624
GATA3: 2625
KRT7: 3855
NANOG: 79923
OCT4: 5460
SUSD2: 56241"
  },
  {
    "caption": "(D) Enrichment of control-sgRNA (n=5) and Slf2-sgRNA (n=6) transduced HSPCs over time.",
    "ncbi_link": "Slf2: 226151"
  },
  {
    "caption": "(E) Kaplan-Meier curves of overall survival of mice transplanted with Eµ-myc;Rosa26Cas9 HSPCs transduced with control-sgRNA (n=15) or sgRNA targeting Slf2 (n=6). p < 0.0001, log-rank (Mantel-Cox) test.",
    "ncbi_link": "myc: 
Cas9: 69900935
Rosa26: 14910
Slf2: 226151"
  },
  {
    "caption": "(F) Immunohistochemical analysis of Slf2-sgRNA lymphomas described in Figure 2E. Representative example of three analyzed Slf2-sgRNA lymphomas.",
    "ncbi_link": "Slf2: 226151"
  },
  {
    "caption": "(B, C) Kaplan-Meier overall survival curves of the indicated cohorts of DLBCL patients (Lenz, NEJM). DLBCL patients were classified according to SLF2 or SLF1 mRNA expression. P-value was determined by log-rank (Mantel-Cox) test.",
    "ncbi_link": "SLF1: 84250
SLF2: 55719"
  },
  {
    "caption": "(E) Mafosphamide dose-response curves of SLF2KO and control SU-DHL-5 cells. Cells were treated with mafosphamide (MAF; 0, 31.25, 62.5, 125, 250, 500, 1000, 2000, 4000 ng/ml) for 48 hours and viability was determined by DAPI staining and flow cytometry measurement. Error bars represent SD from three independent experiments.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(A) Immunoblot analysis of U-2-OS cells following CRISPR/Cas9 mediated knockout of SLF2 upon DRB treatment (0.5 µM) for indicated times with the indicated antibodies.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
SLF2: 55719"
  },
  {
    "caption": "(E) Immunoblot analysis of human SU-DHL-5 control and SLF2KO cell lines upon DRB treatment (0.5 µM) for indicated time points with the indicated antibodies.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(A) TMT-based MS results of chromatin fractions from SU-DHL-5 control and SU-DHL-5 SLF2KO cells. Volcano plot depicting depleted chromatin-associated proteins. Significant hits are shown by red dots (depleted in SLF2KO cells). Proteins belonging to the DDR and cell cycle regulation are labeled. Experiments were performed in triplicates.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(E) Immunoblot analysis of human SU-DHL-5 control and SLF2KO whole cell fractions with the indicated antibodies. (F) Immunoblot analysis of human chromatin fractions of SU-DHL-5 control and SLF2KO cell lines with the indicated antibodies.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(E) SUMO inhibitor (SUMOi (ML-093); 0, 6.25, 12.5, 25, 50, 100, 200, 400, 800 nM) dose response curves of SLF2KO and control SU-DHL-5 cells. Cells were treated with increasing concentrations of SUMOi for 72 hours and viability was determined by negative DAPI staining and flow cytometry measurement. Error bars represent SD from three independent experiments.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(F) Quantification of flow cytometry results for DAPI and Annexin V staining in human SLF2KO and control SU-DHL-5 cells after 12.5 nM of SUMOi treatment for 72 hours. P-value determined by unpaired t-test. Error bars represent SD from three independent experiments.",
    "ncbi_link": "SLF2: 55719"
  },
  {
    "caption": "(B) Immunoblot analysis of human SU-DHL-5 control and CLSPNKO cell lines upon DRB treatment (0.5µM) for indicated time points with the indicated antibodies.",
    "ncbi_link": "CLSPN: 63967"
  },
  {
    "caption": "(F) SUMO inhibitor (SUMOi, TAK981; 0, 6.25, 12.5, 25, 50, 100, 200, 400, 800 nM) dose-response curves of CLSPNKO and control SU-DHL-5 cells. Cells were treated with increasing concentrations of SUMOi for 72 hours and viability was determined by negative of DAPI staining and flow cytometry measurement. Error bars represent SD from three independent experiments. (G) Mafosphamide dose-response curves of CLSPNKO and control SU-DHL-5 cells. Cells were treated with mafosphamide (MAF; 0, 31.25, 62.5, 125, 250, 500, 1000, 2000, 4000 ng/ml) for 48 hours and viability was determined by negative of DAPI staining and flow cytometry measurement. Error bars represent SD from three independent experiments.",
    "ncbi_link": "CLSPN: 63967"
  },
  {
    "caption": "(G) Quantification of cell viability measured by celltiterGlo from primary murine Eµ-Myc lymphoma derived cells co-treated with indicated concentrations of SUMOi and Rabusertib for 72 hours. Bar plots represent cell viability relative to the DMSO treated control cells. Error bars represent SD from three independent experiments. P-value was determined by ANOVA test; Tukey's post hoc test.",
    "ncbi_link": "Myc: "
  },
  {
    "caption": "(A) Pearson correlation between ZEB1 and MITF mRNA expression in 61 melanomacell lines available through the CCLE.",
    "ncbi_link": "MITF: 4286
ZEB1: 6935"
  },
  {
    "caption": "(B) ZEB1, ZEB2, TWIST1 and MITF expression in a panel of BRAFV600-mutated melanomacells assessed by Western blot. GLO and C-09.10cells are patient-derived short-term cultures. Actin was used as a loading control.",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "(C) Quantitative PCR analyses of ZEB1, ZEB2, TWIST1and MITF in the same panel of cell lines. mRNA expression levels are represented relatively to C-09.10 cells, in which the levels were arbitrarily fixed at 1 (n=3, mean ± SD). The dotted line separates ZEB1high (left) and ZEB1low (right) cell lines.",
    "ncbi_link": "MITF: 4286
ZEB1: 6935"
  },
  {
    "caption": "(D) Tukey box plot of ZEB1, ZEB2, TWIST1, and MITF mRNA expression according to the IC50 of the drug (µM) administered (BRAFi/MEKi), in melanoma cell lines from the CCLE (n=28) (Student's t-Test). High ZEB1, low ZEB2, and low MITF expression levels were correlated with BRAFi (PLX4720) and MEKi (AZD6244) resistance. PLX4720 is an analog of PLX4032.",
    "ncbi_link": "MITF: 4286
TWIST1: 7291
ZEB1: 6935
ZEB2: 9839"
  },
  {
    "caption": "(E) IC50 values of PLX4032 (µM) in the panel of BRAFV600 melanoma cells as determined by ATP assay (n=3, mean ± SD). For SKMEL24 and WM793, IC50 was >8µM.",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "(A) Pearson correlation between ZEB1 and MITF mRNA expression levels in 467 melanomatumors from TCGA data set.",
    "ncbi_link": "MITF: 4286
ZEB1: 6935"
  },
  {
    "caption": "(C) Representative pictures of ZEB1 immunostaining in BRAFV600 tumors from patients, classified in ZEB1 high, int and low subgroups, based on the intensity of ZEB1 staining and on the percentage of cells positive for ZEB1. Scale bar = 80 µm. (D) Pie charts representing the distribution of ZEB1 alone (upper part), or ZEB1 and TWIST1 (lower part) immunohistochemistry staining in tumors according to their initial response to vemurafenib +/- cobimetinib treatment. ZEB1 +/- TWIST1 levels are higher in MAPKi primary resistant melanomas (initial non-responders) compared to tumors that initially respond to treatment (n=70, Fisher's exact test).",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "(C) Quantitative PCR analyses of ZEB1and MITF in A375-R and SKMEL5-Rversus the parental naive cells, and in GOKA and ESP cells. mRNA expression levels are represented as arbitrary units (a.u). Statistical difference relative to sensitive A375 cells is shown (n=3, mean ± SD, Student's t-test).",
    "ncbi_link": "MITF: 4286
ZEB1: 6935"
  },
  {
    "caption": "(A) A375 cells were infected with retroviruses expressing ZEB1. Western blot analyses of ZEB1 and p75. GAPDH was used as a loading control.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(B) Quantitative PCR analyses of MITF, p75, ABCB5 and JARID1B upon ZEB1 expression. mRNA expression levels are represented relatively to control cells, in which the levels were fixed at 1 (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "ABCB5: 340273
JARID1B: 10765
MITF: 4286
p75: 4804
ZEB1: 6935"
  },
  {
    "caption": "(C) Soft agar colony formation assay upon ZEB1 expression. Scale bar = 200 µm. Histograms represent quantitative analyses (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(D) 2 x 106 Control or ZEB1-overexpressing A375 cells were injected subcutaneously into nude mice. The mean tumor volume for 5 mice is represented ± SEM (Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(E) Western blot analyses of ZEB1, MITF, P-ERK, and TWIST1 levels in control or ZEB1-expressing cells +/- 150 nM PLX4032 treatment for 24 h. GAPDH was used as a loading control.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(F) FACS analyses of p75 cell surface expression upon ZEB1 overexpression, after 10 days treatment with or without 150 nM PLX4032. Bar chart representing the mean percentage of p75-high, int and low cells from 2 independent experiments (Fisher's Exact Test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(G) Control or ZEB1-overexpressing A375 cells were transfected with control or p75-siRNA. p75 and MITF expression levels were was analyzed by quantitative PCR after 48 h. mRNA expression levels are represented relatively to control cells transfected with siRNA Control, in which the levels were fixed at 1 (mean ± SD, n=2).",
    "ncbi_link": "MITF: 4286
p75: 4804
ZEB1: 6935"
  },
  {
    "caption": "(H) Clonogenic assay +/- PLX4032 (150 nM), +/- GDC-0973 (5 nM) treatment for 10 days. The graphs represent the mean number of colonies (± SD) in 3 independent experiments (Student's t-test). (I) Number of weeks of chronic exposure to PLX4032 before emergence of resistance in control or ZEB1-expressing cells (n=3, Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(A) C-09.10 short-term culture cells were infected with retroviruses expressing ZEB1. Western blot analyses of ZEB1 and p75. GAPDH was used as a loading control.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(B) Quantitative PCR analyses of MITF and p75 upon ZEB1 expression. mRNA expression levels are represented relatively to control cells (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "MITF: 4286
p75: 4804
ZEB1: 6935"
  },
  {
    "caption": "(C) Soft agar colony formation assay following ZEB1 expression. Scale bar = 200 µm. Histograms represent quantitative analyses (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(D) FACS analyses of p75 cell surface expression upon ZEB1 overexpression. Bar chart representing the mean percentage of p75-high, int, low and negative cells from 2 independent experiments (Fisher's exact test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(A) A375 cells were infected with retroviruses expressing a control or ZEB1-shRNA. Western blot analyses of ZEB1 and p75 upon ZEB1 knock-down. GAPDH was used as a loading control. High and low exposures (exp) for p75 are shown.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(B) Quantitative PCR analyses of MITF, p75, ABCB5 and JARID1B upon ZEB1 knock-down. mRNA expression levels are represented relatively to shRNA control cells (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "ABCB5: 340273
JARID1B: 10765
MITF: 4286
p75: 4804
ZEB1: 6935"
  },
  {
    "caption": "(C) FACS analyses of p75 expression upon ZEB1 knock-down. Bar chart representing the mean percentage of p75-high, int and low cells from 2 independent experiments (Fisher's exact test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(D) Soft agar colony formation assay upon ZEB1 knock-down. Scale bar = 200 µm. Histograms represent quantitative analyses (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(E) 2 x 106 Control or ZEB1-shRNA A375 cells were injected subcutaneously into nude mice. The mean tumor volume for 5 mice is represented (± SEM). (Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(F) A375 cells were infected with an IPTG-inducible ZEB1-shRNA. Left panel: Western blot analyses of ZEB1 expression ± IPTG (100µM) treatment for 6 days. Actin was used as a loading control. Right panel: 2 x 106 IPTG-inducible shRNA-Control or shRNA-ZEB1A375 cells were injected subcutaneously into nude mice. When the tumor reached 5 mm in diameter, ZEB1 expression was silenced by adding IPTG (10 mM) into the drinking water for 20 days. The mean tumor volume for 5 mice is represented (± SEM). (Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(G) SKMEL5 cells expressing an IPTG-inducible ZEB1-shRNA were treated with IPTG (100µM) for 10 days (+IPTG), then IPTG was removed (-IPTG) and ZEB1, MITF and p75 expression levels were analyzed by Western blot and/or quantitative PCR analyses. GAPDH was used as a protein loading control, mRNA expression levels are represented relatively to untreated cells, in which the levels were fixed at 1 (mean ± SD, n=2).",
    "ncbi_link": "MITF: 4286
p75: 4804
ZEB1: 6935"
  },
  {
    "caption": "(A) Western blot analyses of ZEB1 and P-ERK in shRNA-control or shRNA-ZEB1-expressing A375 cells +/- 150 nM PLX4032 treatment for 24 h. GAPDH was used as a loading control.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(B) Soft agar colony formation assay in A375 cells in the presence or absence of PLX4032 (150 nM). Scale bar = 100 µm. Histograms represent quantitative analyses (mean ± SD, n=3, Student's t-test). (C) Number of weeks of chronic exposure to PLX4032 before emergence of resistance in control or shRNA-ZEB1-expressing cells (n=3, Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(D) RPMI7951, A375-R and SKMEL5-R were infected with a retrovirus encoding a constitutive shRNA-ZEB1. Short-term cultures of GOKA and ESP cells, derived from vemurafenib-resistant patients, were infected with a lentivirus encoding an IPTG-inducible shRNA-ZEB1. Western blot analyses showing efficient ZEB1 knock-down in the different models, ±IPTG (200µM), ±PLX4032 (3µM) as indicated. Induction of cell death was assessed by PARP cleavage. GAPDH or actin were used as loading control.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(F) Western blot analyses of ZEB1, p75 and quantitative PCR analyses of MITF in shRNA-Control or shRNA-ZEB1ESPvemurafenib-resistant patient-derived short-term culture cells. Actin was used as a loading control. mRNA expression levels are represented relatively to control cells (mean ± SD, n=3, Student's t-test).",
    "ncbi_link": "MITF: 4286
ZEB1: 6935"
  },
  {
    "caption": "(G) 2,5 x 106 shRNA-Control or shRNA-ZEB1ESPvemurafenib-resistant cells were injected subcutaneously in nude mice. When the tumor reached 5 mm in diameter, ZEB1 expression was silenced by providing mice with IPTG (10 mM) in their drinking water and orally administering vemurafenib (50 mg/kg) daily for 4 weeks. The mean tumor volume for 5 mice is represented (± SEM). (Student's t-test).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(H) Upper part: Western blot analyses of ZEB1 in shRNA-Control (1 to 4) or shRNA-ZEB1 (5 to 8) ESPxenografttumors, showing efficient ZEB1 knock-down directly in the tumors, after IPTG ±PLX4032 treatment in vivo. Lower part: Representative pictures of ZEB1 immunostaining in shRNA-Control or shRNA-ZEB1tumors, after IPTG treatment in vivo. Scale bar = 40µm.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "UCSC genome browser tracks with examples of IL-2 pDHSs within the Locus Control Region (LCR) within the Rad50 gene which controls the Th2 cytokines Il13, Il4 and Il5, plus IL-2 pDHSs within the Tnfrsf9 and Cish loci. IL-2 pDHSs are highlighted with blue boxes.",
    "ncbi_link": "Cish: 12700
Il13: 16163
Il4: 16189
Il5: 16191
Rad50: 19360
Tnfrsf9: 21942"
  },
  {
    "caption": "Jund mRNA levels in TB IL-2 and TB IL-2nil. Standard deviation is shown from the mean of 3 samples. P-values were calculated from the RNA-seq data using Limma with Benjamini-Hochberg correction for multiple testing.",
    "ncbi_link": "Jund: 16478"
  },
  {
    "caption": "UCSC genome browser tracks at the Il13/Il4/Il5 Th2 cytokine locus LCR (indicated by the grey box within the Rad50 gene), Gzmb and Il24 showing DNase-Seq and ChIP-Seq for STAT5 and JUND in TB IL-2 and TB IL-2nil. Replicate JUND and STAT5 ChIP-Seq tracks are shown for TB IL-2.",
    "ncbi_link": "Gzmb: 14939
Il13: 16163
Il24: 93672
Il4: 16189
Il5: 16191
Rad50: 19360"
  },
  {
    "caption": "Examples of IL-2 iDHSs which are proximal to IL-2 pDHSs at the Csf2/Il2 and Il10 loci. IL-2 iDHSs are highlighted in red and IL-2 pDHSs in blue.",
    "ncbi_link": "Csf2: 1437
Il10: 16153
Il2: 16183"
  },
  {
    "caption": "UCSC genome browser tracks showing DNase-seq and RNA-seq at the Socs1 (E) and Sell loci (F).",
    "ncbi_link": "Sell: 20343
Socs1: 12703"
  },
  {
    "caption": "UCSC genome browser tracks showing DNase-Seq and RNA-Seq at the IL-2 regulated genes Csf2/Il3 and at the LCR within the Rad50 gene (grey box) which controls the Th2 cytokines Il13, Il4 and Il5. IL-2 pDHSs are highlighted in blue and IL-2 iDHSs in red.",
    "ncbi_link": "Csf2: 12981
Il13: 16163
Il3: 16187
Il4: 16189
Il5: 16191
Rad50: 19360"
  },
  {
    "caption": "UCSC genome browser tracks with DNase-Seq data for TB IL-7 and TB IL-7nil showing examples of IL-2 pDHSs within the Locus Control Region (LCR) within the Rad50 gene which controls the Th2 cytokines Il13, Il4 and Il5, plus IL-2 pDHSs within the Tnfrsf9 and Cish loci (C) IL-2 pDHSs are highlighted with blue boxes.",
    "ncbi_link": "Cish: 12700
Il13: 16163
IL-2: 16183
Il4: 16189
Il5: 16191
Rad50: 19360
Tnfrsf9: 21942"
  },
  {
    "caption": "UCSC genome browser tracks with DNase-Seq data for TB IL-7 and TB IL-7nil showing examples of IL-2 pDHSs within the Locus Control Region (LCR) within the non-primed control regions from the CD3 gene cluster and the Tbp locus (D). IL-2 pDHSs are highlighted with blue boxes.",
    "ncbi_link": "CD3: 12501
Tbp: 21374"
  },
  {
    "caption": "Flow cytometric analysis of IL-7Rα expression by 2W1S-specific CD44hi CD4 T cells in the presence or absence of cre recombinase.",
    "ncbi_link": "cre recombinase: 2777477"
  },
  {
    "caption": "Average number of 2W1S-specific cells recovered/mouse after sorting 3 replicate samples of Il7rf/f compared to CD4creERT2 x Il7rf/f . Errors bars indicate the standard deviation.",
    "ncbi_link": "CD4: 12504
cre: 2777477
ERT2: 2099
Il7r: 16197"
  },
  {
    "caption": "UCSC genome browser tracks at loci with IL-2 pDHSs showing replicate ATAC-Seq samples for CD4creERT2 x Il7rf/f memory T cells, Il7rf/f control memory T cells, replicate DNase-Seq samples for TB IL-2 and TB IL-2nil and TB IL-2 and TB IL‑2nil STAT5 ChIP-Seq samples. The grey boxes signify IL-2 pDHSs which diminish after disruption of the Il7r gene.",
    "ncbi_link": "CD4: 12504
cre: 2777477
ERT2: 2099
Il7r: 16197"
  },
  {
    "caption": "UCSC genome browser tracks showing ChIP-Seq and DNase-Seq at the LCR within the Rad50 gene which controls the Il4/Il13/Il5 Th2 cytokine locus, and also Il17a, Il12rb2 and Tbx21. The grey boxes indicate IL-2 pDHSs which bind STAT5 in Th0 cells and other STAT proteins in other T cell lineages.",
    "ncbi_link": "Il12rb2: 16162
Il13: 16163
Il17a: 16171
IL-2: 16183
Il4: 16189
Il5: 16191
Rad50: 19360
Tbx21: 57765"
  },
  {
    "caption": "mRNA expression levels of JUN family transcription factors. Normalised TPM is shown for TB IL-2, TB IL2nil, TB+ IL-2 and TB+ IL-2nil. Standard deviation is shown for 3 replicates.",
    "ncbi_link": "JUN: 16476"
  },
  {
    "caption": "Average JUND ChIP-Seq signal at the 1000 IL-2 pDHSs in Junb+/+CD4Cre (Junb WT) and Junbf/fCD4Cre (Junb KO) Th17 cells.",
    "ncbi_link": "CD4: 12504
Cre: 2777477
Junb: 16477"
  },
  {
    "caption": "Genome browser tracks showing open chromatin (DNase-Seq or ATAC-Seq) and ChIP-Seq in Th0, Th1 and Th17 cells at the Il17a locus (Carr et al., 2017, Ciofani et al., 2012, Vahedi et al., 2012). The grey box indicates a DHS which binds JUND.",
    "ncbi_link": "Il17a: 16171"
  },
  {
    "caption": "Fold change in gene expression in TB+ IL-2 cells for Jund -/- compared to Jund+/+ mice. Data from 2 replicates are shown.",
    "ncbi_link": "Jund: 16478"
  },
  {
    "caption": "Genome browser tracks showing open chromatin (DNase-Seq or ATAC-Seq) and ChIP-Seq in Th0, Th1 and Th17 cells at the Irf8 locus. The grey box indicates an IL-2 pDHS which binds JUND.",
    "ncbi_link": "Irf8: 15900"
  },
  {
    "caption": "The mRNA expression profiling on specific markers of stem cells (B) and transit amplifying cells captured on P7 incisors CLE followed by analysis using real-time RT-PCR (C). qRT- PCR results are in arbitrary values after normalization for GapDH. Statistics was performed on triplicates using one-way ANOVA followed by Bonferroni's test.",
    "ncbi_link": "GapDH: "
  },
  {
    "caption": "Tamoxifen induced IFT88 deletion strategy (top panel) and representative images of Sox2 (green) and Ki67 (red) immunostaining on CLE regions of the indicated mouse strains (bottom panels). Dotted lines, basement membrane. Note the significant reduction of both Sox2 and Ki67 immunolabeling upon deletion of IFT88.",
    "ncbi_link": "IFT88: 21821"
  },
  {
    "caption": "Representative IF staining of Prom1 using antibodies directed either its extracellular loop (clone 13A4, green) or cytoplasmic C-terminal end (Biorbyt, Orb129549, red) on transit amplifying cell regions of the WT vs. Prom1 KO mice. Samples are counterstained with DAPI (blue). Note the lack of Prom1 labeling in Prom1 KO mice.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "The mRNA profiling on shRNA-meditated Prom1 knockdown (3 different shRNAs were used, marked as NO.1, 2 and 3) in cultured CLESCs. qRT- PCR results are in arbitrary values after normalization for GapDH.",
    "ncbi_link": "GapDH: 
Prom1: 19126"
  },
  {
    "caption": "protein profiling on shRNA-meditated Prom1 knockdown (3 different shRNAs were used, marked as NO.1, 2 and 3) in cultured CLESCs. The immunoblotting was performed with anti-Prom1 C-terminal antibody. β-actin was used as loading control (F). Molecular mass markers are indicated.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Representative images (A) and quantitative analysis (B) of IF staining and 3D reconstruction on Sox2-positive region for WT vs. Prom1 KO mice. Ant: Anterior; Post: Posterior (A). Statistics was performed using Student's t-test: **, p < 0.01. Data are represented as mean and standard deviation.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Representative IF double staining of Sox 2 (green) and Ki67 (red) on the and transit amplifying cell regions of WT vs. Prom1 KO mice on frontal sections. Samples are counterstained with DAPI (blue). Quantification of Ki67+ cell number in Sox2-positive region based on IF data from WT and Prom1 KO mice (C).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Passaging capacity analysis of the CLESCs derived from P7 WT and Prom1 KO mice. Note the passages of cells derived from WT animals are still ongoing while those from Prom1 KO mice were arrested at the first passage. Arrows indicated cells were still under passaging while blunt bars represent cells could not be passaged and stopped at the indicated passage.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Clonogenicity assay for colony number (B) and size (C) after the first the passage of CLESCs derived from WT vs. Prom1 KO mice in the absence or presence of SHH (100ng/ml). Cells were seeded in triplicate on 24-well plates as 5,000 cell/per well.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Flow cytometry analysis of Ki67-Fucci CLESCs at different cell cycle stages in cells transfected with empty vector or full length Prom1. As a result, >95% of the events have been included in the analysis. The accuracy of the strategy has been validated by two independent researchers for IF quantification using Fiji 1.0 software.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Size of individual cilia in stem cell and transit amplifying cell regions of WT and Prom1 KO mice (A) and their density in the respective regions (B). 3 animals were analyzed for each genotype. The number of quantified cilia is indicated (n).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Clonogenicity analysis of CLESCs treated with siArl13b and its siControl. Colonies were stained with crystal violet",
    "ncbi_link": "Arl13b: 68146"
  },
  {
    "caption": "siRNA knockdown efficiency of Arl13b (E) in Ki67 FUCCI-CLESCs was evaluated real-time RT-PCR analysis. The results are in arbitrary values after normalization for GapDH",
    "ncbi_link": "GapDH: 
Arl13b: 68146"
  },
  {
    "caption": "siRNA knockdown efficiency of Hdac6 (F) in Ki67 FUCCI-CLESCs was evaluated real-time RT-PCR analysis. The results are in arbitrary values after normalization for GapDH",
    "ncbi_link": "GapDH: 
Hdac6: 15185"
  },
  {
    "caption": "Representative IF double staining and 3D reconstruction of the Prom1 (green) and AcTub (red) at the apical domain of polarized MDCK cells expressing Prom1 and its K138Q mutant (top panels). Black-white inserts show Prom1 signals only. Same cells were analyzed by SEM (bottom panels). Note that Prom1 is asymmetrically distributed along the primary cilium (white arrows) as observed in vivo (see Fig 2C) and mutation K138Q significantly impacts on the primary cilium length. MV, microvilli.",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "IF staining and 3D reconstruction of AcTub-labeled (red) primary cilium at the apical membrane of parental MDCK cells (MDCK) and those cells transfected with Prom1 or its K138Q mutant. The images were used to quantify the primary cilium length (Appendix Figs S6B and C). Arrows indicate primary cilia with more than 4 μm in length.",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "Parental MDCK cells or those transfected with Prom1 or K138Q mutant were grown for 7 dpc Cells were observed by phase-contrast microscopy (A) Box-whisker plots show the number of domes per 600 mm2 (A). Three images were analyzed per experiment (n = 4). 4X magnification (inset in panel A).",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "Parental MDCK cells or those transfected with Prom1 or K138Q mutant were grown for 7 dpc Cells were observed by SEM (B, top panels) or confocal laser scanning microscopy after DAPI staining (B, bottom panels, Individual cells within a given dome are indicated (B, top panels) and were quantified using three different planes (bottom, centre and top) of DAPI-labeled nuclei (B, bottom panels).",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "Parental MDCK cells or those transfected with Prom1 or K138Q mutant were grown for 7 dpc (A-C) or as indicated (D). confocal laser scanning microscopy after DAPI staining Domes of similar size were evaluated (C). Means and standard deviations are displayed. 15 domes per independent experiment were examined (n = 3). Cell density at a given time of culture (7, 10 and 14 days) was determined by counting DAPI-labeled nuclei per 0.1 mm2 (D, n = 4).",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "Mutation in the Hdac6-binding site of Prom1 increases the release of Prom1+ vesicles. 16 h-conditioned medium was subjected to differential centrifugation for 5 min at 300 x g (P1); 20 min at 1,200 x g (P2); 30 min at 10,000 x g (P3) and 1 h at 200,000 x g (P4). In parallel, detergent cell lysates were prepared. The entire pellets and 1/40 of cell lysates were analyzed by immunoblotting using antibodies against human Prom1, AcTub and β-actin (F). Molecular mass markers are indicated. All three proteins were detected in the vesicle fractions (P3 and P4) suggesting Prom1+ vesicles are released from primary cilia and microvilli.",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "Mutation in the Hdac6-binding site of Prom1 increases the release of Prom1+ vesicles. 16 h-conditioned medium was subjected to differential centrifugation for 5 min at 300 x g (P1); 20 min at 1,200 x g (P2); 30 min at 10,000 x g (P3) and 1 h at 200,000 x g (P4). In parallel, detergent cell lysates were prepared. The release of Prom1+ vesicles was quantified using its immunoreactivities associated with cell and vesicle fractions (G)",
    "ncbi_link": "Prom1: 8842"
  },
  {
    "caption": "The mRNA expression of SHH effector genes (Gli1/2 and Glis1-3) on laser microdissection captured samples were evaluated by real-time RT-PCR analysis. The results are in arbitrary values after normalization for GapDH. Each sample was isolated from distinct mice (n = 3).",
    "ncbi_link": "GapDH: 
Gli1: 14632
Glis1: 230587"
  },
  {
    "caption": "Volume of Sox2-positive region on the lower incisor CLE at P7 was evaluated in WT vs. Glis2 KO mice upon IF staining. Number of animals analyzed is indicated (n).",
    "ncbi_link": "Glis2: 83396"
  },
  {
    "caption": "Representative IF staining of Prom1 using specific antibodies targeting either its extracellular loop (top panels, green) or cytoplasmic C-terminal end (bottom panels, red) on the stem cell and transit amplifying cell regions of lower incisor CLE at P7 WT and Glis2 KO mice. Samples are counterstained with DAPI (blue). Dotted lines, basement membrane. Arrowheads marks approximate boundary of stem cell regions.",
    "ncbi_link": "Glis2: 83396"
  },
  {
    "caption": "Representative IF double staining of Glis2 (red) and AcTub (green) as a marker of primary cilia in stem cell region of WT vs. Prom1 KO mice. Note the reduction of Glis2 expression in Prom1-deficient animals.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "PCR array analyses were performed on LCM captured P7 CLE of Prom1 and Glis2 KO vs. WT mice (n = 3). Arrows indicated genes with expression changed for more than 2 folder increase or decrease.",
    "ncbi_link": "Glis2: 83396
Prom1: 19126"
  },
  {
    "caption": "PCR array analyses were performed on LCM captured P7 CLE of Prom1 and Glis2 KO vs. WT mice (n = 3). The mRNA expression of gene significantly changed in the PCR array (in (C)) (D) was evaluated in WT, Prom1 and Glis2 KO mice by real-time RT-PCR analysis. Each sample was isolated from distinct mice (n = 3). The results are in arbitrary values after normalization for GapDH.",
    "ncbi_link": "GapDH: 
Glis2: 83396
Prom1: 19126"
  },
  {
    "caption": "PCR array analyses were performed on LCM captured P7 CLE of Prom1 and Glis2 KO vs. WT mice (n = 3). The mRNA expression of gene significantly changed in the Stat pathway members (E) was evaluated in WT, Prom1 and Glis2 KO mice by real-time RT-PCR analysis. Each sample was isolated from distinct mice (n = 3). The results are in arbitrary values after normalization for GapDH.",
    "ncbi_link": "GapDH: 
Glis2: 83396
Prom1: 19126"
  },
  {
    "caption": "Chromatin IP analysis of binding of Glis2 to Stat3 promoter (see Appendix Fig S9D) in the absence or presence of SHH at different concentration as indicated on triplicated samples, using specific anti-Glis2 antibodies and rabbit IgG as control.",
    "ncbi_link": "Stat3: 20848"
  },
  {
    "caption": "D. SIM  images of 8325-4∆sle1 and 8325-4∆ftsK S. aureus cells incubated with purified HisTag-Sle1-SP. External addition of the protein split the tetrads  observed in sle1  and ftsK  knock-out strains. Scale bars, 1μm.",
    "ncbi_link": "sle1: 3919100
ftsK: 3920535"
  },
  {
    "caption": "A. Absence of Sle1   in (from top to bottom) autolytic,  cell wall or total cellular extracts  and  spent medium of 8325-4∆sle1  and  8325-4∆ftsK  mutants, but not in the parental strain  NCTC8325-4, was confirmed by  western blot analysis using an anti-Sle1  antibody. All  western blot  experiments were performed with three biological replicates and representative images are shown.",
    "ncbi_link": "sle1: 3919100
ftsK: 3920535"
  },
  {
    "caption": "B. Quantification of Sle1  total cellular levels, detected by western blot  (representative gel on the bottom) in S. aureus mutant 8325-4∆ftsK and ClpX  inactivated mutants 8325-4 ClpXR95C and 8325-4∆ftsK ClpXR95C showing that ClpX  inactivation restores the presence of Sle1  in the ftsK  deletion mutant. Data information: Graphs show ratio between Sle1  amount in different samples versus the amount in parental strain  NCTC8325-4 indicated by dashed line. Data represented in scatter dot plot column graphs, where column height represents mean, and error bars are the standard deviation. Data from at least four biological replicates.",
    "ncbi_link": "ClpX: 3919696
ftsK: 3920535"
  },
  {
    "caption": "C. Quantification of Sle1  total cellular levels, detected by western blot (representative gel on the bottom) in FtsK  C-terminal deletion (8325-4∆ftsKc) or inactivated (8325-4FtsKK971A) mutants showing that Sle1  levels increase in the absence of FtsK  DNA translocase activity. Data information: Graphs show ratio between Sle1  amount in different samples versus the amount in parental strain NCTC8325-4 indicated by dashed line. Data represented in scatter dot plot column graphs, where column height represents mean, and error bars are the standard deviation. Data from at least four biological replicates.",
    "ncbi_link": "FtsK: 3920535
ftsK: 3920535"
  },
  {
    "caption": "A. Total protein extracts of strains NCTC8325-4, 8325-4 TF-GFP, 8325-4 MurC-GFP  and 8325-4 TF-GFP Sle1Tn (the latter lacking Sle1) were immunoprecipitated  with GFP-Trap Magnetic Particles. Western blot  analysis of the pulled-downed  fractions using antibodies against Sle1  and GFP  shows that Sle1  is pulled down with TF-GFP  but not with negative control MurC-GFP, suggesting a specific interaction  between TF  and Sle1.",
    "ncbi_link": "GFP: 
MurC: 3920534
Sle1: 3919100
TF: 3919697"
  },
  {
    "caption": "B. Total protein extracts of strains 8325-4 TF-3XFLAG,  8325-4 GFP-FtsK TF-3XFLAG, 8325-4sfgfp-ftsK  and 8325-4 TF-3XFLAG GFP-HU  (Input extracts, bottom panel) were immunoprecipitated  with DYKDDDDK Fab-Trap Agarose  that binds FLAG-tagged proteins. Western blot  analysis of the pulled-downed fractions (top panels) using antibodies against FLAG  and GFP  shows that GFP-FtsK, but not the negative control GFP-HU, is pulled down with TF-3XFLAG, suggesting an interaction between TF  and FtsK. For each assay, a representative image of three independent biological replicates is shown.",
    "ncbi_link": "FLAG: 
GFP: 
gfp: 
HU: 3920245
ftsK: 3920535
FtsK: 3920535
TF: 3919697"
  },
  {
    "caption": "A. SIM  images of cells expressing TF-GFP  labeled with membrane  dye FM5-95. TF-GFP  forms a gradient towards the septum  in the background of parental strain NCTC8325-4 (8325-4 TF-GFP, top panels). This localization  pattern is lost in cells lacking FtsK  (8325-4∆ftsK TF-GFP, middle panels), but not in 8325-4∆ftsKc TF-GFP  mutant, expressing FtsK  without its C-terminal domain (bottom panels). Scale bars, 1 µm.",
    "ncbi_link": "GFP: 
FtsK: 3920535
ftsK: 3920535
TF: 3919697"
  },
  {
    "caption": "B. Deconvolved epifluorescence images of  live cells  of parental strain  8325-4 Sle1-3XFLAG ∆spa and TF  deletion mutant 8325-4 Sle1-3XFLAG ∆spa ∆tig, producing Sle1-3XFLAG as the sole Sle1   copy in the cell. Normal localization  pattern of Sle1   (enriched at midcell, top panel) is altered in the absence of TF  (bottom panel) with the protein becoming more dispersed over the cell surface. See image S1 for more images of Sle1-3XFLAG surface localization  in the parental strain and the negative control of the  immunofluorescence assay. Cells were incubated with fluorescent D-amino acid HADA, which is incorporated into peptidoglycan, for cell wall visualization (colored blue). Cell surface Sle1-3XFLAG  was detected with Anti-FLAG  Monoclonal Antibody-Alexa Fluor 488 (colored green, projection of a 33 slices Z-stack shown). Scale bars, 1 µm.",
    "ncbi_link": "FLAG: 
spa: 
Sle1: 3919100
TF: 3919697
tig: 3919697"
  },
  {
    "caption": "D. Frequency of cells in each  cell cycle phase in the TF  knockout mutant 8325-4Δtig  and NCTC8325-4  parental strain, showing that the TF  mutant is delayed in cell cycle phase 3, taking longer to split the division septum. Data from three biological replicates of NCTC8325-4 (Ntotal=728) and 8325-4Δtig (Ntotal=699). Data represented in column graphs where column height represents mean and error bars are the standard deviation.",
    "ncbi_link": "tig: 3919697
TF: 3919697"
  },
  {
    "caption": "C. SIM  image and heat map representation of TF-GFP localization  in  8325-4 TF-GFP  cells grown in the presence or absence of  nalidixic acid, showing the loss of TF-GFP  gradient towards the septum  in most cells grown in the presence of the antibiotic. Scale bars, 1 µm. Heatmaps represent the average of TF-GFP localization  in 50 cells in phase 2 of the cell cycle. The color scale depicts the average normalized TF-GFP  fluorescence signal in each pixel, ranging between 0 and 1. The fraction of the area of each cell model where the normalized signal intensity is above 70% of the maximum signal is 0.47 and 0.61 in the absence or presence of  nalidixic acid, respectively, confirming that TF-GFP  becomes more dispersed over the cytoplasm  in the presence of the antibiotic.",
    "ncbi_link": "GFP: 
TF: 3919697"
  },
  {
    "caption": "D. Confocal time lapse microscopy images of HeLa cells stably expressing H2B-mCherry (red) and a microtubule marker (α-Tub-eGFP; green) 48 h after transfection of miR-449a mimic, or non-targeting control siRNA. Scale bar, 10 μm.E. Quantification of spindle rotation and duration from prometaphase to anaphase onset in time-lapse movies as in D. miR-449a mimic promotes spindle rotation. Duration from prometaphase to anaphase onset was defined as the time from nuclear envelope breakdown to anaphase onset. Spindle rotation during metaphase was measured as described in methods. Individual data points correspond to single cells (n ≥ 72 in all conditions). Normality was tested with Kolmogorov-Smirnov test. Variance between samples was tested using F test. Significance was tested by Welch's t test: p-value = 2.598e-06 comparing spindle rotation of negative control versus miR-449a mimic-transfected cells (all data points are compared). p-value = 0.0005621 (for cells with prometaphase-anaphase onset duration lower than 60 min.",
    "ncbi_link": "miR-449a: 554213"
  },
  {
    "caption": "A. The expression levels of endogenous miR-34/449 family members were measured by RT-qPCR in ventricular zone samples derived by laser microdissection of mouse cortices at E14. The levels of the different miR-34/449 family members and miR-7a-1, a highly expressed miRNA relevant in cortical progenitor biology, were determined. All concentrations were normalized (norm.) using miR-7a-1 concentration (n = 8 cortices, 2 different litters). Error bars indicate standard error.",
    "ncbi_link": "miR-7a-1: 723902"
  },
  {
    "caption": "B, C. Expression analysis of miR-34/449 by in situ hybridization using locked nucleic acid (LNA) probes in wild type cortices at E14. Mature miR-449, miR-34b and miR-34c are preferentially expressed in the subventricular (SVZ) and ventricular (VZ) zones of the neocortex. Scale bar, 50 μm (A), 10 μm (B).",
    "ncbi_link": "miR-34b: 723849
miR-34c: 723932
miR-449: 100190765///723868"
  },
  {
    "caption": "B, C. Expression analysis of miR-34/449 by in situ hybridization using locked nucleic acid (LNA) probes in wild type cortices at E14. Mature miR-449, miR-34b and miR-34c are preferentially expressed in the subventricular (SVZ) and ventricular (VZ) zones of the neocortex. Scale bar, 50 μm (B), 10 μm (C).",
    "ncbi_link": "miR-34b: 723849
miR-34c: 723932
miR-449: 100190765///723868"
  },
  {
    "caption": "D, E. Brains of adult mice (P23), and quantification of brain weight. Dots indicate individual brains; red line indicates median. Mice lacking miR-449abc and miR-34bc (DKO) or miR-449abc, miR-34bc, and miR-34a (TKO) have significantly smaller brains compared to littermate controls (Het). Significance was tested by Pairwaise t-test with Bonferroni correction; Het (n = 6 brains, 2 different litters) vs. DKO (n = 4 brains, 2 different litters) p-value = 0.00215; Het (n = 6 brains, 2 different litters) vs. TKO (n = 4 brains, 2 different litters) p-value = 0.00054. Subfigure G was statistically tested as in E. * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001.",
    "ncbi_link": "miR-34a: 723848
miR-34b: 723849
miR-449a: 723868"
  },
  {
    "caption": "A. Confocal images of coronal sections from E16 brains of miR-34/449 KO mice and littermate controls (Het), stained with anti-Satb2-antibody to label neurons of layers II-IV (green) and DAPI to label all cell nuclei (blue). Scale bars: 50 μm.B. Quantification of the number of Satb2-positive cells per 100 μm ventricular zone surface. Bars indicate mean ± SEM, as for all quantifications shown in this figure; n = 3 brains per genotype group, from two independent litters. Data was normalized (norm.) to the ventricular zone surface analyzed (100 µm) and relativized to the heterozygous control average value. Significance was tested by Welch's t test: p-value = 0.01146 (Het vs. KO) (n = 4 cortices per genotype group, 2 independent litters). All subfigures were statistically tested as in B. * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001.",
    "ncbi_link": "miR-34: 723932///723849///723848"
  },
  {
    "caption": "K. 3D reconstruction of a dividing radial glial progenitor at early anaphase. A coronal section of an E14 brain of a heterozygous control mouse was stained with anti-phospho-Vimentin antibody (red), anti-γ-tubulin antibody (green/yellow), phalloidin (magenta), and DAPI (blue) and imaged by 3D confocal microscopy. \"s\" indicates spindle axis, \"α\" indicates angle relative to ventricular surface plane, which was determined by a vector path as indicated by thin white lines located on the left side of the image. Yellow dots highlight the centrosomes of the spindle poles from the analyzed dividing cell. Scale bars: 5 μm.L. Quantification of spindle orientation in radial glial cells as in K for E14 brains of miR-34/449 KO and littermate controls (Het). Each dot represents a single dividing cell; p-value = 3.166e-05 (Het vs. KO) (n = 131 vs. 107 cells, n = 4 brains per genotype group, 2 independent litters).",
    "ncbi_link": "miR-34: 723932///723849///723848"
  },
  {
    "caption": "A. Quantification of mRNA expression by RT-qPCR of candidate miR-34/449 targets that might regulate spindle orientation in E14 cortex samples from miR-34/449 KO mice compared with littermate controls (Het). Expression was normlaized (norm.) to Phosphoglycerate kinase (PGK) mRNA levels. Significance was tested by Welch's t test: p = 0.009756 (JAM-A (Het) vs. JAM-A (KO)), all the rest Het vs. KO comparisons p=n.s. (n = 4 cortices per genotype group, 2 independent litters). All subfigures were statistically tested as in A. * indicates p ≤ 0.05, ** indicates p ≤ 0.01, *** indicates p ≤ 0.001. Red bar indicates median.",
    "ncbi_link": "JAM-A: 16456
miR-34: 723932///723849///723848
PGK: 18655"
  },
  {
    "caption": "B. RT-qPCR quantification of JAM-A mRNA expression in HeLa cells 48 h after transfection of miR-449a mimic compared to cells transfected with non-targeting negative control siRNA. JAM-A mRNA Expression was normalized (norm.) to Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA levels. p = 0.0001218 (Neg. ctrol. vs. miR-449a mimic) (n = 9 measurements from 3 independent replicates).",
    "ncbi_link": "JAM-A: 50848
GAPDH: 2597
miR-449a: 554213"
  },
  {
    "caption": "C, D. mouse J110 cells were transfected with either miR-449a mimic or a negative control mimic. Whole cell extracts were subjected to immunoblot analysis to detect endogenous JAM-A and ACTIN. ACTIN was used to normalize JAM-A expression (norm.) as loading control. p = 0.04454 (Neg. ctrol. vs. miR-449a mimic) (n = 4 independent wells, 2 independent transfections).",
    "ncbi_link": "miR-449a: 723868"
  },
  {
    "caption": "E, F. HeLa cells were cotransfected with either miR-449a mimic or a negative control mimic, together with JAM-A-GFP fusion protein and GFP. Whole cell extracts were subjected to immunoblot analysis to detect GFP. GFP was used to normalize (norm.) by transfection efficiency as loading control. p = 0.001176 (JAM-A WT Neg. ctrol. vs. miR-449a mimic) (n = 9 independent wells, 4 independent transfections).",
    "ncbi_link": "JAM-A: 50848
miR-449a: 554213"
  },
  {
    "caption": "G, H. Confocal images of coronal sections from E14 brains of wild type mice stained with anti-JAM-A antibody (green), phalloidin to label actin (gray) and DAPI to label cell nuclei (blue). Scale bars: 10 μm (G), 5 μm (H).I. Quantification of JAM-A protein expression in the ventricular zone of E14 brain coronal sections from miR-34/449 KO mice compared with littermate controls (Het) by immunofluorescence. ACTIN (phalloidin signal) was used to normalize (norm.) the expresion levels of JAM-A. p = 0.04842 (n = 5 (KO) or 7 (het) cortices per genotype group, 3 independent litters).",
    "ncbi_link": "miR-34: 723932///723849///723848"
  },
  {
    "caption": "A, D. Confocal time lapse images of metaphase HeLa cells stably expressing a centriole marker (Centrin2-GFP; green), the microtubule marker (α-tubulin-mRFP; red) and no extra protein (A) or mouse JAM-A (D), 48 h after transfection of miR-449a mimic, JAM-A siRNA, or non-targeting negative control siRNA. Scale bar, 10 μm.B, E. Quantification of spindle rotation for cells as shown in A and D. Each dot represents a single cell. Red bar indicates median. Significance was tested by Pairwise t-test with Bonferroni correction. p-value = 2e-11 (Neg. control versus miR449 mimic), p-value = 0.01928 (Neg. control versus JAM-A siRNA), p-value = 0.17492 (Neg. control versus miR449 mimic, under JAM-A overexpression). * indicates p ≤ 0.05; ** p ≤ 0.01; p*** p ≤ 0.001 for all panels.C, F. Cumulative histograms of mitotic duration from nuclear envelope breakdown until anaphase onset, measured for cells as shown in A and D; n ≥ 20 cells for all conditions, 2 independent replicates.",
    "ncbi_link": "JAM-A: 16456
JAM-A: 50848
miR-449a: 554213"
  },
  {
    "caption": "Representative images of fluorescence in-situ hybridization of  ADPGK-AS1  (magenta) and nuclei  (blue) in IL-4 stimulated  M2-like macrophages. β-actin served as the cytoplasmic  control and MALAT1   as the nuclear  control. Scale bar = 10 µm.",
    "ncbi_link": "β-actin: 60
ADPGK-AS1: 100287559
MALAT1: 378938"
  },
  {
    "caption": "RNA expression  analysis of ADPGK-AS1, 47S ribosomal RNA (nuclear  control), and β-Tubulin (cytoplasmic  control) in IL-4 stimulated M2-like macrophages  after subcellular fractionation. n = 3 independent experiments. Data represent the percentage of total detected RNA.",
    "ncbi_link": "47S ribosomal RNA: 
ADPGK-AS1: 100287559
β-Tubulin: 203068"
  },
  {
    "caption": "Subcellular fractionation of IL-4-stimulated M2-like macrophages  and isolation and analysis of ADPGK-AS1  abundance in the cytoplasmic  and mitochondrial  fractions The mitochondrial  encoded RNA mtATP6  served as the mitochondrial  control and β-tubulin as the cytoplasmic  control. n = 3 independent experiments, Data represent the percentage of total detected RNA.",
    "ncbi_link": "ADPGK-AS1: 100287559
ATP6: 4508
β-tubulin: 203068"
  },
  {
    "caption": "(A) Validation of the ADPGK-AS1-interacting  protein MRPL35  by RNA immunoprecipitation (RIP) with followed by qPCR  for ADPGK-AS1. n = 4 independent experiments, ***p ≤ 0.001 compared with IgG control.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(B, C) Co-staining for ADPGK-AS1 (magenta) and MRPL35  or MRPL15  (yellow) with respective fluorescence intensity across  co-stained macrophages  (see white line) for  ADPGK-AS1  and MRPL35  or MRPL15. Scale bar = 10 µm (left), 5 µm (right).",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(C, Representative images and quantification of mitochondria  by MitoTracker  (red) in THP1  control and ADPGK-AS1  OE cells. Nuclei  were stained  with DAPI  (blue). Scale bar = 200 µm (left), 100 µm (right, magnification).",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "D) Representative images and quantification of mitochondria  by TOM20  (green) in THP1  control and ADPGK-AS1 OE cells. Nuclei  were stained  with DAPI  (blue). Scale bar = 200 µm (left), 100 µm (right, magnification).",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(E) Representative immunoblot  for mitochondrial protein expression (TOM20, αb-crystallin, PCG-1, MRPL35, cytochrome C) in THP1  control and ADPGK-AS1 OE cells. n = 4 independent experiments.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(G) Gene expression  analysis (fold change) of mitochondrially  encoded genes (ND1, ND2, ND4, ATP6, ATP8, CO1, CO2, CyB) after isolation of mtDNA  from THP1  control and ADPGK-AS1 OE cells. n = 3 independent experiments. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 compared with control.",
    "ncbi_link": "ADPGK-AS1: 100287559
ATP6: 4508
ATP8: 4509
CO1: 4512
CO2: 4513
CyB: 4519
ND1: 4535
ND2: 4536
ND4: 4538"
  },
  {
    "caption": "I) full oxygen  consumption plot (n = 8) by the seahorse assay in THP1  control and ADPGK-AS1  OE cells. **p ≤ 0.01, ***p ≤ 0.001 compared with control.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(K) Representative confocal  fluorescence images and quantification of mitochondrial  shape with the mitochondrial  marker TOM20  (yellow) in THP1  control and ADPGK-AS1  OE cells. Nuclei  were stained  with DAPI  (blue). n = 35 cells, Scale bar=10µm (left), 5µm (magnification, right).",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(L)  Transmission electron microscopy images of mitochondrial  shapes in THP1  control and ADPGK-AS1 OE cells. n = 4 cells, Scale bar = 5 µm (left), 1 µm (right, magnification).",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(B) Expression  analysis of ADPGK-AS1  and MRPL35  (fold change) in THP1  control and  ADPGK-AS1 OE macrophages  transfected with a siRNA against ADPGK-AS1, MRPL35  or negative control. n = 4 independent experiments. ***p ≤ 0.001 compared with ADPGK-AS1  OE siRNA control.",
    "ncbi_link": "ADPGK-AS1: 100287559
MRPL35: 51318"
  },
  {
    "caption": "(C) Representative images of JC-1    monomers (green) and aggregates (red) in THP1  control and ADPGK-AS1 overexpressing macrophages  transfected with a siRNA against ADPGK-AS1, MRPL35, or negative control. Scale bar = 100 µm.",
    "ncbi_link": "ADPGK-AS1: 100287559
MRPL35: 51318"
  },
  {
    "caption": "(E) Representative images (left panel) and quantification (right panel) of ROS  accumulation in THP1  control and ADPGK-AS1 OE cells transfected with a siRNA against  ADPGK-AS1, MRPL35, or negative control. n = 7. ***p ≤ 0.001 compared to control.",
    "ncbi_link": "ADPGK-AS1: 100287559
MRPL35: 51318"
  },
  {
    "caption": "(F) Spare capacity  (oxygen consumption rate) measured with the  seahorse assay in THP1  control and ADPGK-AS1  OE cells transfected with a siRNA against ADPGK-AS1, MRPL35, or negative control. n = 3 independent experiments. ***p ≤ 0.001 compared with control, §p ≤ 0.05, §§§p ≤ 0.001 compared with  ADPGK-AS1 OE siRNA negative control.",
    "ncbi_link": "ADPGK-AS1: 100287559
MRPL35: 51318"
  },
  {
    "caption": "(B) mRNA expression  analysis (ΔCT) of macrophage  markers (TNFα, IL-8, CD206, CSF-1R) in co-cultured PBMC-derived macrophages  with tumor cells or macrophage  control (M0). n = 4 biological replicates. *p ≤ 0.05, **p ≤ 0.01 compared with M0.",
    "ncbi_link": "CSF-1R: 1436
IL-8: 3576
CD206: 4360
TNFα: 7124"
  },
  {
    "caption": "(C) Expression  of ADPGK-AS1 lncRNA in macrophages  co-cultured with tumor cells (A549) or macrophage  controls (M0). n = 4 biological replicates. *p ≤ 0.05, compared with M0.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(G) Expression  of IDH  mRNA in A549  cells transfected with siRNA specific for IDH  (IDH  KD) or negative control. n = 5 independent experiments. ***p ≤ 0.001 compared with A549  control.",
    "ncbi_link": "IDH: 3417"
  },
  {
    "caption": "(H) RNA expression analysis of ADPGK-AS1 in THP1 macrophages  stimulated to have an M1-like  or  M2-like phenotype, untreated (M0) or treated with conditioned medium  (CM) of A549  cells transfected with a siRNA specific for IDH  (IDH  KD) or negative control. n = 5 biological replicates. ***p ≤ 0.001, compared with tumor cell control CM.",
    "ncbi_link": "ADPGK-AS1: 100287559
IDH: 3417"
  },
  {
    "caption": "(A, B) mRNA expression  analysis (ΔCT) of M1   (TNFα, IL-8, CXCL10) and M2   (CSF-1R, CD206, IL-10, ALOX15, TGFβ, IL-1Ra) macrophage  marker genes in THP1  control and ADPGK-AS1 OE cells. n = 4 independent experiments. *p ≤ 0.05, ***p ≤ 0.001 compared with control.",
    "ncbi_link": "ADPGK-AS1: 100287559
ALOX15: 246
CSF-1R: 1436
CXCL10: 3627
IL-8: 3576
IL-10: 3586
IL-1Ra: 3557
CD206: 4360
TGFβ: 7040
TNFα: 7124"
  },
  {
    "caption": "(E) Migration  (right panel) of A549  cells treated with CM from THP1  control or ADPGK-AS1  OE macrophages. Representative membrane  images are shown in the left panel. n = 5 independent experiments. ***p ≤ 0.001 compared with control. Scale bar = 400 µm.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(G-H) mRNA expression  analysis (ΔCT) of M1   (TNFα, IL-8, CD80, CCR7) and M2   (CSF-1R, CD206, IL-10, TGFβ) macrophage  marker genes in primary M1-like (M1) and   M2-like (M2) macrophages  transfected with antisense LNA GapmeRs specific for ADPGK-AS1  or negative control. n = 5 biological replicates, *p ≤ 0.05, **p ≤ 0.01, compared to M2  control.",
    "ncbi_link": "ADPGK-AS1: 100287559
CCR7: 1236
CD80: 941
CSF-1R: 1436
IL-8: 3576
IL-10: 3586
CD206: 4360
TGFβ: 7040
TNFα: 7124"
  },
  {
    "caption": "(K) Migration  (right panel) of tumor cells (A549) treated with CM from PBMC-derived M1-like (M1) or  M2-like  (M2) macrophages  transfected with antisense LNA GapmeRs specific for ADPGK-AS1  or negative control. Representative membrane  images are shown in the left panel. n = 5 biological replicates. *p ≤ 0.05, compared with M2   control. Scale bar = 400 µm.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(C) Representative brightfield  images of tumors (scale bar = 2mm) and fluorescence images (Ki67, cleaved caspase 3, scale bar = 100 µm; cleaved caspase 3 (green) and cytokeratin 18  (magenta), scale bar = 50 µm) and LDH enzyme activity  (scale bar = 25 µm) after co-injection with M1-like (M1) or  M2-like (M2) macrophages  transfected with antisense LNA GapmeRs specific for ADPGK-AS1  or negative control (ctrl) together with A549  tumor cells or A549  cells alone as a control.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(F) RNA expression  analysis of ADPGK-AS1  and MRPL35  in tumor PCLS treated with antisense LNA GapmeRs specific for ADPGK-AS1 or a negative control or seeded with THP1  control or ADPGK-AS1 OE cells. n = 5 independent experiments. *p ≤ 0.05, ***p ≤ 0.001 compared with control GapmeR, §p ≤ 0.05, §§§p ≤ 0.001 compared with EV control.",
    "ncbi_link": "ADPGK-AS1: 100287559
MRPL35: 51318"
  },
  {
    "caption": "(G) Multispectral flow cytometry  analysis of  M1-like  and M2-like macrophage populations in tumor PCLS treated with antisense LNA GapmeRs specific for ADPGK-AS1  or a negative control or seeded with THP1  control or ADPGK-AS1  OE cells. n = 6 biological replicates. *p ≤ 0.05 compared with Gapmer negative control, §p ≤ 0.05 compared with EV control.",
    "ncbi_link": "ADPGK-AS1: 100287559"
  },
  {
    "caption": "(C) Detection of sAPPα, sNrCAM and mNrCAM in ADAM10 cKO neuronal supernatants and lysates at 7 days in vitro (DIV7). The neurons prepared from floxed ADAM10 (ADAM10 fl/fl) mice were infected with a lentivirus encoding improved Cre recombinase (iCre) or a control GFP lentivirus at DIV2. Conditioned media were collected for 48 h. Densitometric quantifications of the Western Blots are shown (** p < 0.01; *** p < 0.001; **** p < 0.0001, two-sided students t-test n = 6-8).",
    "ncbi_link": "GFP: 
ADAM10: 11487
Cre: 2777477"
  },
  {
    "caption": "HEK 293 cells were transfected with a C-terminally VSV-tagged NrCAM construct or empty vector. Cells were then treated with DAPT (1 µM), GI254023x (5 µM), either substances or solvent for 24 h. The C-terminal NrCAM-fragment was detected with an antibody against the VSV-tag. Representative Western Blots are shown.",
    "ncbi_link": "VSV: 
NrCAM: 4897"
  },
  {
    "caption": "(A) ADAM10 fl/fl neurons were treated with an iCre (to induce an ADAM10 KO), or a control lentivirus at DIV2. At DIV7, cell surface proteins were labeled with biotin and enriched by streptavidin pull-down. The biotinylated proteins were detected by immunoblotting. Total lysates were analyzed to compare mNrCAM's surface/lysate levels. Densitometric quantifications of the Western Blots are shown. Two-sided students t-test (**** p < 0.0001, n = 7). Given are mean +/- the standard error of them mean. The mean levels of solvent treated cells were set to 1.",
    "ncbi_link": "ADAM10: 11487
Cre: 2777477"
  },
  {
    "caption": "(C) Workflow of the neurite outgrowth assay. (D) Representative pictures of single neurites at time-point 0h (DIV3) and 24h (DIV4). Neurons were infected 4h after plating with lentiviruses encoding GFP (to visualize the neurons) together with shRNA expression cassettes (sh1 and sh2) targeting either NrCAM or carrying a scrambled (scr) control construct. Images of neurites were taken at three days in vitro (DIV3) and 24h later at DIV4. In order to study the effect of ADAM10 on neurite outgrowth, neurons were treated with the ADAM10 inhibitor GI254023x, or vehicle (control), at DIV3, after taking the first pictures with an epifluorescent microscope. The differences in neurite length were calculated as absolute values (neurite length at 24h minus neurite length of 0h) for individual neurites passing through the middle channels of the chambers. Only neurites that had already entered the main channel at 0h and had not yet left those channels at 0h were considered. The red arrows indicate the start and the end of the respective length measurements. The scale bar indicates 40 µm. (E) One-way ANOVA with post hoc Dunnett's test. Given are mean +/- the standard error of them mean (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001, n-numbers for each condition are shown in the graph in 3E).",
    "ncbi_link": "GFP: 
NrCAM: 319504"
  },
  {
    "caption": "HEK293 cells were transiently transfected with hNrCAM, FLAG-tagged hTSPAN15, either plasmids or the empty vector. Detection of sAPPα and sNrCAM in the conditioned media and ADAM10 in the cell lysate. Densitometric quantification of the Western Blots are shown (** p < 0.01), (*** p < 0.001), (**** p < 0.0001), two-sided students t-test, or one-way ANOVA with post hoc Dunnett's test (n = 6). Given are mean +/- the standard error of them mean. The mean levels of solvent treated cells were set to 1. Representative Western Blots are shown.",
    "ncbi_link": "FLAG: 
NrCAM: 4897
TSPAN15: 23555"
  },
  {
    "caption": "(G) Percentages of control (n = 210), Mcrs1-KD (n = 182), and Mcrs1-rescue (n = 201) oocytes that underwent GVBD and PBE. The bars are representing the mean ± SEM. The P-values were calculated using Student's t-test. GVBD%: ***P = 0.0003; *P = 0.01, PB1%: *P = 0.03; *P = 0.02.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(A) Representative images of the occurrence of GVBD in control, Mcrs1-KD, and Mcrs1-rescue (Mcrs1 siRNA + Mcrs1 mRNA) oocytes at 3 h following release from IBMX. Scale bar, 100 μm. (B) The incidence of GVBD at 1, 2, and 3 h post-IBMX release in control (n = 155), Mcrs1-KD (n = 157), and Mcrs1-rescue (n = 150) oocytes.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(D) Expression levels of CDK1 in Mcrs1-KD and control oocytes. The bars represent the mean (± SEM) of 5 biological replicates. The P-values were calculated using Student's t-test. *P = 0.01. (E) Expression levels of p-CDK1(Y15) in Mcrs1-KD and control oocytes at 1 h following release from IBMX (200 oocytes per sample). **P = 0.006. (F) Expression levels of cyclin B1 in control and Mcrs1-KD oocytes at 1 h following release from IBMX (200 oocytes per sample). The bars represent the mean (± SEM) of 3 biological replicates. The P-values were calculated using Student's t-test. **P = 0.0042.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(I) The incidence of GVBD at 1, 2, and 3 h post-IBMX release in control oocytes (n = 112), Mcrs1-KD oocytes (n = 98), and Mcrs1-KD oocytes treated with 5 mM WEE1-1N-4 (n = 102). (J) The incidence of GVBD at 1, 2, and 3 h post-IBMX release in control (n = 123), Mcrs1-KD (n = 134), and Mcrs1 siRNA + cyclin B1-GFP (n = 95) oocytes. (K) The incidence of GVBD at 1, 2, and 3 h post-IBMX release in control (n = 92), Mcrs1-KD (n = 97), and Mcrs1 siRNA + cyclin B1-GFP oocytes treated with 5 mM WEE1-1N-4 (n = 106).",
    "ncbi_link": "GFP: 
cyclin B1: 268697
Mcrs1: 51812"
  },
  {
    "caption": "(B) Detection of newly synthesized RNAs by EU incorporation in control, Mcrs1-KD, and Mcrs1-rescue GV oocytes. The scattergram shows the relative fluorescence intensity of EU in control (n = 43), Mcrs1-KD (n = 52), and Mcrs1-rescue (n = 30) GV oocytes. Scale bar, 10 μm. ***P = 0.0001.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(C) Immunofluorescence analysis of H3K4me2 in control and Mcrs1-KD oocytes. Scale bar, 10 μm. Relative fluorescence intensity of H3K4me2 signals in control (n = 26) and Mcrs1-KD (n = 30) GV oocytes. ***P = 0.0001.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(E) Immunofluorescence analysis of H3K9me2 in control and Mcrs1-KD oocytes. Scale bar, 10 μm. Relative fluorescence intensity of H3K9me2 signals in control (n = 29) and Mcrs1-KD (n = 22) GV oocytes. **P = 0.0035. (F) Immunofluorescence analysis of H4K16ac in control and Mcrs1-KD oocytes. Scale bar, 10 μm. Relative fluorescence intensity of H4K16ac signals in control (n = 30) and Mcrs1-KD (n = 28) GV oocytes. *P = 0.022.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(G) Immunofluorescence analysis of HDAC2 in control and Mcrs1-KD oocytes. Scale bar, 10 μm. Relative fluorescence intensity of HDAC2 signals in control (n = 27) and Mcrs1-KD (n = 24) GV oocytes. ***P = 0.0005.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(A) Representative images of spindle assembly at 3 h post-release from IBMX in control and Mcrs1-KD oocytes. Scale bar, 20 μm.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(G) Immunofluorescence analysis of H3S10ph and α-tubulin in control and Mcrs1-KD oocytes. Scale bar, 20 μm. The scattergram shows the relative fluorescence intensity of H3S10ph signals in control (n = 21) and Mcrs1-KD (n = 23) oocytes. *P = 0.017.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(H) Immunofluorescence analysis of γ-tubulin and α-tubulin in control and Mcrs1-KD oocytes. Scale bar, 20 μm. The histogram shows the percentages of control (n = 55) and Mcrs1-KD (n = 63) oocytes with abnormal γ-tubulin. *P = 0.014. (I) Immunofluorescence analysis of acetylated tubulin and α-tubulin in control and Mcrs1-KD oocytes. Scale bar, 20 μm. The scattergram shows the relative fluorescence intensity of acetylated tubulin signals in control (n = 83) and Mcrs1-KD (n = 66) oocytes. **P = 0.0046.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(C) Levels of p-Aurka and p-Aurkc in control and Mcrs1-KD MI oocytes. The blots were probed with anti-p-Aurora A/B/C and anti-actin antibodies. (D) Co-IP was performed with an anti-Mcrs1 antibody. The immunoblots of protein precipitates were probed with an anti-Aurka antibody.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(G) Percentages of control (n = 92), Mcrs1-KD (n = 73), and Aurka-rescue (n = 67) oocytes that underwent PBE. *P = 0.033; *P = 0.018.",
    "ncbi_link": "Aurka: 20878
Mcrs1: 51812"
  },
  {
    "caption": "(H) Percentages of control (n = 69), Mcrs1-KD (n = 76), and Aurka-rescue (n = 43) oocytes with abnormal spindles. *P = 0.018; *P = 0.024.",
    "ncbi_link": "Aurka: 20878
Mcrs1: 51812"
  },
  {
    "caption": "(K) Immunofluorescence analysis of Kif2A in control and Mcrs1-KD oocytes. Scale bar, 20 μm. The histogram shows the percentages of control (n = 50) and Mcrs1-KD (n = 61) oocytes with abnormal Kif2A. **P = 0.003.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "(L) Immunofluorescence analysis of TPX2 and α-tubulin in control and Mcrs1-KD oocytes. Scale bar, 20 μm. The scattergram shows the relative fluorescence intensity of TPX2 signals in control (n = 48) and Mcrs1-KD (n = 52) oocytes.",
    "ncbi_link": "Mcrs1: 51812"
  },
  {
    "caption": "Analysis of long-term multi-lineage HSC potential in E11.5 Sl/Sl AGM+VU. Irradiated CD45.1 syngeneic mice were transplanted with 1 e.e. of wild type, Sl/+ or Sl/Sl CD45.2+ AGM+VU cells. PB chimerism is represented as the percentage of donor CD45.2+ cells among total CD45+ cells, 16 weeks after transplant. A total of 14 recipients were transplanted with wild type or Sl/+ cells and 8 with Sl/Sl cells, over 4 independent experiments. Wild type is represented with a circle, Sl/+ a triangle and Sl/Sl with a square. Tail somite range: 9-17 (+/+, Sl/+); 10-17 (Sl/Sl). *:p=0.027, one-tailed Mann-Whitney's U test; p=0.055, two-tailed Mann-Whitney's U test.",
    "ncbi_link": "CD45.1: 19264"
  },
  {
    "caption": "Confocal whole-mount immunofluorescence (WM-IF) analysis of Kitl-tdTomato expression in the E8.5 (6-7sp) conceptus (maximum intensity 3D projection from a 500μm-thick Z-stack). Kitl-tdTomato expression (red) is seen in the YS, allantois (a; from which the umbilical artery derives), and para-aortic splanchnopleura (PAS) of Kitl-tdTomato::23GFP transgenic concepti (the embryo proper, from which the head has been removed, is outlined with a purple dashed line). The 23GFP transgene (green) labels the YS blood islands (bi; yellow dashed line); this GFP reporter is transcribed from a heterologous hsp68 promoter under the spatiotemporal control of the Runx1 hematopoietic +23 enhancer, resulting in GFP expression in all primitive erythroid(-fated) cells, hemogenic endothelium, and emerging HSPCs[2,74]. Endothelial cells (CD31+) are in white. Arrowheads indicate the paired aortae (pa). Purple boxed area is magnified in (B); yellow boxed area is magnified in (C). Scale bar: 100μm. N=2 embryos analyzed. Single 2.5μm-thick Z slice from the region highlighted in the purple box in (A). Arrowheads indicate Kitl-tdTomato+ CD31+ endothelial cells in one of the paired aortae (pa). Scale bar: 25μm. Single 2.5μm-thick Z slice from the region highlighted in the yellow box in (A), showing Kitl-tdTomato expression in the E8.5 YS BI. Arrowheads indicate Kitl-tdTomato+ CD31+ endothelial cells; the arrow indicates a Kitl-tdTomato+ perivascular cell. Scale bar: 25μm. Single 2.5μm-thick Z slice of 10.5 (35sp) YS (WM-IF) showing Kitl-tdTomato (red), Kit (white) and CD31 (green) expression. Arrowheads indicate Kitl-tdTomato+ CD31+ endothelial cells. N=3 embryos analyzed. Scale bar: 50μm.",
    "ncbi_link": "GFP: 
Kitl: 
tdTomato: 
Runx1: 12394"
  },
  {
    "caption": "Confocal immunofluorescence analysis of cryosections through the AGM region of E10.5 (34-36sp) Kitl-tdTomato transgenic embryos. Arrowheads indicate Kitl-tdTomato+ CD31+ endothelial cells (top), Kitl-tdTomato+ PDGFR-β+ (middle) or Kitl-tdTomato+ α-SMA+ (bottom) perivascular smooth muscle cells. Scale bars: 25μm or 50μm (PDGFR-β panel). N>6 embryos analyzed.",
    "ncbi_link": "tdTomato: 
Kitl: 17311"
  },
  {
    "caption": "Confocal immunofluorescence analysis of Kitl-tdTomato expression in the E10.5 FL. A cryosection through a E10.5 (35-36sp) Kitl-tdTomato transgenic FL is shown. Arrowheads indicate Kitl-tdTomato+ CD31+ Kit- endothelial cells. Asterisks indicate Kitl-tdTomato+ CD31- Kit- mesenchymal cells or hepatoblasts. Note proximity of Kitl-tdTomato+ cells and Kit+ hematopoietic cells. Scale bars: 50μm (left panel), 25μm (magnified inset). N>5 embryos analyzed.",
    "ncbi_link": "Kitl: 
tdTomato: "
  },
  {
    "caption": "Left: number of Ter119- Kit+ CD41+ CD16/32+ EMPs in Tie2Cre::Kitl∆/∆ and control Kitlf/f or f/+ E11.5 YS, determined by flow cytometry. Data are the mean (±SD) of 8 control and 7 Tie2Cre::Kitl∆/∆ YS analyzed individually over 4 independent experiments. Tail somite range: 13-16. Middle: number of pre-HSC type I (Ter119- VE-Cadherin+ Kit+ CD41+ CD45-) and pre-HSC type II/HSC (Ter119- VE-Cadherin+ Kit+ CD41+ CD45+) in Tie2Cre::Kitl∆/∆ and control Kitlf/f or f/+ E11.5 AGM+VU, determined by flow cytometry. Data are the mean (±SD) of 7 control and 5 Tie2Cre::Kitl∆/∆ AGM+VU analyzed individually over 3 independent experiments. Tail somite range: 14-15 (Kitlf/f, f/+); 14-16 (Tie2Cre::Kitl∆/∆). Right: number of Ter119- Kit+ CD41+ CD16/32+ EMPs and Ter119- Kit+ CD41- CD71+ CD44+ early erythroid cells in Tie2Cre::Kitl∆/∆ and control Kitlf/f or f/+ E11.5 FL, determined by flow cytometry. Data are the mean (±SD) of 7 control and 5 Tie2Cre::Kitl∆/∆ FL analyzed individually over 3 independent experiments. Tail somite range: 13-16.",
    "ncbi_link": "Cre: 2777477
Kitl: 17311
Tie2: 21687"
  },
  {
    "caption": "CFU-C numbers in Tie2Cre::Kitl∆/∆ and control Kitlf/f or f/+ E11.5 YS. Data are the mean (±SD) of 6 control and 3 Tie2Cre::Kitl∆/∆ YS plated in duplicate in 2 independent experiments. Tail somite range: 13-16.",
    "ncbi_link": "Cre: 2777477
Kitl: 17311
Tie2: 21687"
  },
  {
    "caption": "Analysis of long-term multi-lineage HSC potential in E11.5 Tie2Cre::Kitl∆/∆ and control Tie2Cre::Kitl∆/+ or Kitlf/f or f/+AGM+VU. Irradiated CD45.1 syngeneic mice were transplanted with 1 e.e. of AGM+VU cells. PB chimerism is represented as the percentage of donor CD45.2+ cells among total CD45+ cells, 16 weeks after transplant. A total of 29 recipients were transplanted with Tie2Cre::Kitl∆/+ or Kitlf/f or f/+ cells and 8 with Tie2Cre::Kitl∆/∆ cells, over 7 independent experiments. Kitlf/f or f/+ is represented with a circle, Tie2Cre::Kitl∆/+ a triangle and Tie2Cre::Kitl∆/∆ with a square. Tail somite range: 12-17 (control); 12-17 (Tie2Cre::Kitl∆/∆).",
    "ncbi_link": "Cre: 2777477
Kitl: 17311
CD45.1: 19264
Tie2: 21687"
  },
  {
    "caption": "CFU-C numbers in Tie2Cre::Kitl∆/∆ and control Kitlf/f or f/+ E11.5 Fl. Data are the mean (±SD) of 7 control and 5 Tie2Cre::Kitl∆/∆ FL plated in duplicate in 3 independent experiments. GEMM: granulocyte, erythroid, monocyte/ macrophage, megakaryocyte; G/M/GM: granulocyte, monocyte/macrophage; Ery: erythroid. Tail somite range: 13-16.",
    "ncbi_link": "Cre: 2777477
Kitl: 17311
Tie2: 21687"
  },
  {
    "caption": "Number of phenotypic LSK, HPC and HSC per FL in E12.5 Tie2Cre::Kitl∆/∆and control (Kitlf/f or f/+) FL, determined by flow cytometry and total FL cell counts. Cells were gated as 7-AAD- Lin- (F4/80- CD3e- Nk1.1- Ter119- Gr-1- B220- CD19-). LSK: Lin- Sca1+ Kit+; HPC: Lin- Sca1+ Kit+ CD48+ CD150- and HSC: Lin- Sca1+ Kit+ CD48- CD150+. Gating strategy is shown in Figure EV4E. Data are the mean (±SD) of 12 control and 6 Tie2Cre::Kitl∆/∆ FLs analyzed individually over 3 independent experiments. Total cellularity of E12.5 Kitlf/f or f/+ (n=14) and Tie2Cre::Kitl∆/∆ (n=11) FL. Error bars represent SD.",
    "ncbi_link": "Cre: 2777477
Kitl: 17311
Tie2: 21687"
  },
  {
    "caption": "E Correlative analyses of IL8 expression in peripheral blood mononuclear cells (PBMCs) to monocyte FSC.",
    "ncbi_link": "IL8: 3579"
  },
  {
    "caption": "F IL8, IL6 and CCL2 mRNA expression in PBMCs from ND and T2D COVID-19 patients.",
    "ncbi_link": "CCL2: 6347
IL8: 3579
IL6: 3569"
  },
  {
    "caption": "A Quantification of IRF5 and IFNB1 mRNA expression in peripheral blood mononuclear cells of non-diabetic (ND) and type 2 diabetic (T2D) COVID-19 patients (A).",
    "ncbi_link": "IFNB1: 3456
IRF5: 3663"
  },
  {
    "caption": " A1) Representative WBs showing DRD2 and RGS9-2 downregulation in adult (P60-P90) Tor1a+/- (+/-) striata, characterized by a reduced torsinA protein level with respect to Tor1a+/+ (+/+) littermates. The striatal level of RGS7 is unchanged. The dot plot shows Tor1a+/- data, normalized to Tor1a+/+ controls of the same experiment. TorsinA: Tor1a+/+ N=7, Tor1a+/- N=6, t test ***P=0.0003; DRD2: Tor1a+/+ N=18, Tor1a+/- N=16, t test **P=0.0029; RGS9-2: Tor1a+/+ N=32, Tor1a+/- N=33, t test *P=0.0115). RGS7: Tor1a+/+ N=7, Tor1a+/- N=7, t test P=0.8721). WB quantification data, expressed as the ratio of protein vs. loading control intensity level, are normalized to the wild-type samples of the same experiment. A2,A3,A4) Time-course of changes in torsinA, DRD2 and RGS9-2 striatal levels along postnatal development. Summary plot data are normalized to the Tor1a+/+ P60 sample of each independent experiment. A2) TorsinA level is significantly reduced in mutants throughout the developmental period considered (P7 N=3; P14-P60 N=4; one-way ANOVA P<0.0001 and Bonferroni's Multiple Comparison Test **P<0.01 at P7, P14 and P60). A3,A4) DRD2 and RGS9-2 levels show parallel courses, with a similar increase from P7 to P21 in Tor1a+/+ as well as Tor1a+/- striatal lysates (P7: DRD2 N=3, RGS9-2 N=4; P14-P21 N=4; one-way ANOVA with Bonferroni's Multiple Comparison Test P>0.05). At P60, a simultaneous reduction of DRD2 and RGS9-2 levels is observed in Tor1a+/- striatal lysates (N=4; Tor1a+/- one sample t test DRD2: *P=0.0250, RGS9-2: *P= 0.0175). WB quantification data, expressed as the ratio of protein vs. loading control intensity level, are normalized to the wild-type P60 sample of the same experiment ",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "B) Representative WB images and the dot plot show downregulation of torsinA, DRD2 and RGS9-2 striatal levels also in adult P60-P90 Tor1a∆gag/+ (∆gag/+) mice. TorsinA: Tor1a+/+ N=10, Tor1a∆gag/+ N=12, t test ***P= 0.0006; DRD2: Tor1a+/+ N=7, Tor1a∆gag/+ N=9, t test *P= 0.0183; RGS9-2: Tor1a+/+ N=10, Tor1a∆gag/+ N=9, t test *P= 0.0192. WB quantification data, expressed as the ratio of protein vs. loading control intensity level, are normalized to the wild-type samples of the same experiment. Mean ± SEM is represented in the graphs",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "C) Left. Representative image of coronal striatal slices of fresh frozen brains of wild-type and Tor1a+/- mice probed with the DRD2 radioligand 3H-spiperone. Scale bar 1.5 mm. (Right) Graph showing DRD2 binding density in Tor1a+/- striatal sections, obtained from the densitometric quantification analysis, expressed as percentage variation compared to control animals",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "A1) Representative WB of RGS9-2, R7BP, and Gβ5 proteins on four Tor1a+/+ and four Tor1a+/- striatal lysates. The bar histogram on the right shows the quantification of the three proteins in each sample. A2) Dot plot showing that Gβ5 striatal levels are unchanged in Tor1a+/- mice (Tor1a+/+ N=11, Tor1a+/- N=10, Mann Whitney test P=0.2453). A3) Conversely, the level of the R7 binding protein R7BP is increased in Tor1a+/- striatum (Tor1a+/+ N=12, Tor1a+/- N=12, t test **P=0.0014). Values are represented as ratio of protein vs. loading control intensity level, normalized to the mean of Tor1a+/+ control values of the same experiment",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "B1) Representative WB of lysates of Tor1a+/+ and Tor1a+/- dorsal striatum slices incubated for 5 hours in the presence (w/ leu) or absence (w/o leu; contralateral striatum) of the protease inhibitor leupeptin. Samples showing enhanced degradation of DRD2 and/or RGS9-2 proteins show additional bands at lower molecular weight. B2) Summary plot reporting mean ± SEM of RGS9-2 and DRD2 protein level values, expressed as the ratio of protein vs. loading control intensity level, normalized to the value of the Tor1a+/+ w/leu sample measured in the same experiment. DRD2: Tor1a+/+ N=4, t test P=0.4376; Tor1a+/- N=4, t test *P=0.0427; RGS9-2: Tor1a+/+ N=5, t test *P=0.0464; Tor1a+/- N=5, t test *P= 0.0190",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "C1, C2, C3, C4) Dot plots showing DRD2, RGS9-2, R7BP and Gβ5 protein levels measured in striatal detergent-resistant-membrane (DRM) preparations from Tor1a+/- (+/-) and WT (+/+) mice (DRD2: Tor1a+/+ N=16, Tor1a+/- N=13, t test P=0.0129; RGS9-2: Tor1a+/+ N=7, Tor1a+/- N=6, t test *P=0.0396; R7BP: Tor1a+/+ N=6, Tor1a+/- N=6, t test ***P=0.0002; Gβ5: Tor1a+/+ N=9, Tor1a+/- N=9, t test P=0.8461)",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "WB analysis of markers of endocytic trafficking and degradative pathway in the dorsal striatum of Tor1a+/- mice. A) The level of β-arrestin 2 (β-Arr2) is not altered (Tor1a+/+ N=11, Tor1a+/- N=12, t test P=0.6796), whereas the level of spinophilin (B) is decreased (Tor1a+/+ N=5, Tor1a+/- N=8, t test *P=0.0151)",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "C) A Sh-RGS9-2-GFP viral preparation injected into the right striatum (+) of C57Bl/6 mice effectively reduces both RGS9-2 and DRD2 protein levels, with respect to the contralateral striatum (-).The summary plot reports mean ± SEM values (RGS9-2: N=4, paired t test *P=0.0100; DRD2: N=4, paired t test *P=0.0432)",
    "ncbi_link": "RGS9-2: 19739"
  },
  {
    "caption": "D) The endosomal marker Rab4 is upregulated in the Tor1a+/- striatum (Tor1a+/+ N=13, Tor1a+/- N=14, t test **P=0.0087)",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "E) Basal levels of markers of the degradative pathway, p62 and LC3-II, show a trend towards upregulation in Tor1a+/- striatal lysates (p62: Tor1a+/+ N=11, Tor1a+/- N=11, t test P=0.2292; LC3-II: Tor1a+/- N=9, Tor1a+/- N=11, t test P=0.1574)",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "F) Treatment with bafilomycin A1 (BafA1) induces a significantly more pronounced increase of LC3-II in Tor1a+/- than in wild-type dorsal striatum slices. BafA1-induced increase in LC3-II level measured in Tor1a+/- slices was normalized to the increase observed in the Tor1a+/+ samples of the same experiment (N=4, one sample t test **P=0.0012)",
    "ncbi_link": "Tor1a: 30931"
  },
  {
    "caption": "dHepaRG-TR-A3A cells were infected with HBV at an MOI of 300 virions/cell. Cells were treated with tetracycline (Tet (A3A)) or/and 300 U/ml IFNα from day 9 to 18 p.i. cccDNA amplicons were analyzed by 3D‑PCR",
    "ncbi_link": "A3A: 200315"
  },
  {
    "caption": "dHepaRG cells were infected with HBV at an MOI of 100 virions/cell and treated 9 days later with 300 U/ml IFNα (B) or 200 U/ml IFNγ (C) for indicated times (h: hours). Expression of indicated genes was analyzed by qRT-PCR relative to TATA-box binding protein (TBP) mRNA (n=6 biological replicates of two independent experiments).",
    "ncbi_link": "TATA-box binding protein: "
  },
  {
    "caption": "dHepaRG cells were infected at an MOI of 100 virions/cell and transduced at day 7 p.i. with an adenoviral vector for expression of shRNA targeting ISG20 (AdV-shISG20). After 2 days, cells were treated with 300 U/ml IFNα or 200 U/ml IFNγ. ISG20 expression was analyzed by western blot after 7 days of IFNα or 12 days of IFNγ treatment, respectively.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "A subsequence of the 3D-PCR amplicon was used as (-) ssDNA oligomer, complementary (+) ssDNA and a dU-containing (‑) ssDNA, where all cytosines were replaced by uracils. These oligomers were digested in vitro with recombinant ISG20 with or without EDTA as indicated.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "dHepaRG-TR-A3A cells were infected with HBV at an MOI of 300 virions/cell and at day 7 p.i. transduced with AdV-ISG20 and treated with tetracycline to induce A3A expression as indicated (± Tet (A3A)) for 7 days. Cell lysates were analyzed for cccDNA after T5 digest (B) and total intracellular HBV DNA (C) by qPCR relative to Prnp (n=5-6 biological replicates from two independent experiments).",
    "ncbi_link": "A3A: 200315
ISG20: 3669
Prnp: 5621"
  },
  {
    "caption": "dHepaRG-TR-A3A cells were infected with wildtype HBV (HBVwt) or HBV∆x at an MOI of 300 virions/cell and transduced on day 7 p.i. with AdV-ISG20 and treated with tetracycline to induce A3A expression as indicated (± Tet (A3A)) for 7 days. HBeAg (E) was measured by ELISA and cccDNA after T5 digest (F) by qPCR relative to Prnp (n=6 biological replicates from two independent experiments).",
    "ncbi_link": "A3A: 200315
ISG20: 3669
Prnp: 5621"
  },
  {
    "caption": "A,B  NAD  and nicotinamide (NAM) levels in heart  of WT (n=5, n=6, respectively), mdx  (n=5, n=5, respectively) and mdx/CD38-/- mice (n=6, n=5, respectively). C,D NAD  and NAM levels in  diaphragm of WT (n=5, n=6, respectively), mdx (n=4, n=5, respectively) and mdx/CD38-/- mice (n=6, n=5, respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; B: Kruskal-Wallis followed by Dunn's test; D: Kruskal-Wallis followed by Mann-Whitney tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "E,F levels of ADP-ribose  (ADPR) (E),  cyclic ADP-ribose  (cADPR) (F) expressed as nmol/mg protein in heart of WT (n=6), mdx (n=5) and  mdx/CD38-/- mice (n=5, n=5, n=6 respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "(G) qPCR analysis of mRNA levels of Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) in  heart  of WT (n=6), mdx (n=5) and mdx/CD38-/- mice (n=5, n=5, n=6 respectively). Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494
SARM1: 237868
Sterile alpha and Toll/interleukin-1 receptor motif-containing 1: 237868"
  },
  {
    "caption": "H,I Levels of ADPR (H), cADPR (I) expressed as nmol/mg protein in  diaphragm  of WT (n=6), mdx (n=5) and  mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; ; I: Welch's ANOVA followed by Welch's t-tests Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "(J) qPCR  analysis mRNA levels of SARM1 in diaphragm of WT (n=6),  mdx (n=5) and mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: J: ANOVA Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494
SARM1: 237868"
  },
  {
    "caption": "M, N qPCR analysis of  CD38  mRNA levels in  heart  (M) and  diaphragm (N) of WT (n=6) and  mdx  (n=5) mice. Data information: Each dot of the graphs represents a mouse and measured in duplicate After normality and variance comparison tests, significance was assessed using: M: unpaired Student's t-test; N: unpaired Welch's t-test. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "A Cardiac  function evaluated by  echocardiography in  mdx/CD38-/- mice: the dot plots show the  left ventricular (LV)  diastolic (A1) and  systolic (A2) inner diameters and LV  ejection (A3) fraction in 7-month-old WT (n=5), mdx  (n=6) and  mdx/CD38-/- (n=10) mice. Data information: : Each dot of the graphs represents a mouse. in duplicate After normality and variance comparison tests, significance was assessed using:A1 ANOVA followed by Fisher's LSD test; A2,A3 Kruskal-Wallis followed by Dunn's test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "B Plasma levels of cardiac  stress biomarkers:  brain natriuretic peptide (BNP) (B1) and cardiac troponin I  (cTnI) (B2) in 7-month-old WT (n=7), mdx (n=6) and mdx/CD38-/- (n=11) mice. Data information: : Each dot of the graphs represents a mouse. After normality and variance comparison tests, significance was assessed using ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "C Cropped images revealed the    collagen (blue) stained by Masson's trichrome staining  in the  heart  of WT,  mdx, and  mdx/CD38-/- mice. Dot plot showing the quantification of heart collagen staining area (% total area) in 7-month-old WT, mdx, and mdx/CD38-/- mice (n=4 per group). Scale bars: 200 µm. Data information: : Each dot of the graphs represents a mouse. in triplicate After normality and variance comparison tests, significance was assessed using ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "D Isoproterenol-induced  heart failure in 3-month-old mice. The Kaplan-Meier  curve shows the survival rate of mdx mice  (NaCl, n=5); mdx  (n=19) and mdx/CD38-/- (n=9) mice following isoproterenol (subcutaneous injection) at 2.5 mg/kg/d for 10 days. Data information: one value/mouse. After normality and variance comparison tests, significance was assessed using D: Log-rank Mantel-Cox test and Log-rank test for trend and Gehan-Breslow-Wilcoxon test ; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "E Histogram showing isoproterenol-induced heart hypertrophy in mdx NaCl (n=5) mice, surviving mdx  (n=9), mdx/CD38-/- NaCl  (n=9) and mdx/CD38-/- (n=9) mice, expressed as heart weight/body weight ratio (HW/BW). Data information: one value/mouse. After normality and variance comparison tests, significance was assessed using Kruskal-Wallis followed by Mann-Whitney tests Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "F Plasma levels of cardiac  stress biomarkers: brain natriuretic peptide (BNP) (F1) and  cardiac troponin I (cTnI) (F2) following isoproterenol treatment in mdx NaCl  (n=5), surviving mdx  (n=8),  mdx/CD38-/- NaCl  (n=5) and mdx/CD38-/- (n=8) mice. Data information: in duplicate After normality and variance comparison tests, significance was assessed using F2 Kruskal-Wallis followed by Mann-Whitney tests; F1: ANOVA followed by Student's/ Welch's t-tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "G,H Time-lapse images recorded by confocal microscopy in \"line scanning mode\", showing Ca2+ sparks and waves in  cardiomyocytes at rest, extracted from  mdx and mdx/CD38-/- mice; scale bars: 10 µM (horizontal), 500 ms (vertical). Bar graphs showing the averaged Ca2+ sparks (G) and waves (H) frequencies in cardiomyocytes  isolated from WT (n=21 cells), mdx (n=28 cells) and mdx/CD38-/- (n=32 cells) mice. Data information: experiments performed in 3  mice of each group. After normality and variance comparison tests, significance was assessed using Kruskal-Wallis followed by Dunn's test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "I Bar graph showing the fractional release following caffeine application in  cardiomyocytes from WT (n=24 cells), mdx (n=33 cells) and mdx/CD38-/- (n=32 cells) mice. Data information: experiments performed in 3 mice of each group. After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; ; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "J Bar graph showing the post-rest potentiation in cardiomyocytes from WT (n=24 cells), mdx (n=28 cells) and mdx/CD38-/- (n=32 cells)  mice. Data information: experiments performed in 3 mice of each group. After normality and variance comparison tests, significance was assessed using: Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "A Measurement of the ventilatory mechanic by barometric plethysmography: dot plots showing  inspiratory (A1) and expiratory times (A2), the relaxation time (A3) and the respiratory frequency (A4) in WT (n=8), mdx (n=11) and mdx/CD38-/- (n=9) mice. Data information: Each dot of the graphs represents a mouse. one value/mouse After normality and variance comparison tests, significance was assessed using: A1,A3 ANOVA followed by Fisher's LSD test; A2, A4 : Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "B Images showing muscle fiber typology revealed by immunostaining. Localization of the slow   MyHC (Type I) fiber and fast   MyHCs (Type IIa and IIb/X) fibers, along with laminin (red) on transverse cross-sections from  diaphragm of WT, mdx and mdx/CD38-/- mice. Scale bars: 100 µm. Histogram showing the percentage of I, IIa and IIb/X fiber type distribution in diaphragm of WT (n=7), mdx (n=6) and mdx/CD38-/- (n=7) mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: ; B: Chi-square test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "C Fiber size distribution in the  diaphragm of WT (n=7), mdx  (n=6) and  mdx/CD38-/- (n=7) mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: C: Kolmogorov-Smirnov test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "D Images revealing the collagen (blue) by Masson's trichrome staining in  diaphragm of WT, mdx, and mdx/CD38-/- mice. Quantification of collagen staining area (% total area) in the diaphragm of WT, mdx  and mdx/CD38-/- mice (n=4 per group). Scale bars: 200 µm. Data information: Each dot of the graphs represents a mouse. D in duplicate; After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "E Embryonic myosin expression: immunostaining showing its localization along with laminin (green) on transverse cross-sections from diaphragm of WT,  mdx and mdx/CD38-/- mice. Scale bars: 50 µm. Histogram showing the relative proportion of embryonic myosin area (% total area) in diaphragm of WT (n=7), mdx  (n=8) and mdx/CD38-/- (n=8) mice. Data information: Each dot of the graphs represents a mouse. E one value/mouse. After normality and variance comparison tests, significance was assessed using: E: Welch's ANOVA followed by Welch's t-tests. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "A Images showing immunostaining  of myeloid cells showing F4/80 (macrophage  marker), Ly-6G/6C (monocyte, granulocyte and neutrophil marker), CD8 (cytotoxic T lymphocyte  marker) and IL-6  positive cells in diaphragm of 7-month-old WT (n=8), mdx (n=8) and mdx/CD38-/- (n=7 or 8 ) mice. Lower panel: histograms quantifying the percentage of F4/80  (A1) mdx/CD38-/- (n=7), LY6 (A2) mdx/CD38-/- (n=8), CD8 (A3) mdx/CD38-/- (n=7), IL-6 (A4) mdx/CD38-/- (n=8) positive cells. Scale bars: 50 µm. Data information: Each dot of the graphs represents a mouse. A one value/mouse After normality and variance comparison tests, significance was assessed using: A1-4: Welch's ANOVA followed by Welch's t-tests; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "B qPCR  analysis of mRNA levels of  interleukin-1β (IL-1ß) (B1) and -6 (IL-6) (B2), cyclin-dependent kinase inhibitor 1 (p21) (B3) transforming growth factor-β  (TGF-β) (B4), and senescence markers (cell-cycle inhibitor p16, INK4a) (B5), Collagen Type I Alpha 1 Chain (Col1a1) (B6) in diaphragm of 20-month-old WT (n=6), mdx (n=5) and mdx/CD38-/- (n=5) mice. Data information: Each dot of the graphs represents a mouse. B in duplicate. After normality and variance comparison tests, significance was assessed using: B1-6: ANOVA followed by Fisher's LSD test. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494
cyclin-dependent kinase inhibitor 1: 12575
p21: 12575
cell-cycle inhibitor p16: 12578
INK4a: 12578
Col1a1: 12842
Collagen Type I Alpha 1 Chain: 12842
IL-1ß: 16176
interleukin-1β: 16176
IL-6: 16193
TGF-β: 21803
transforming growth factor-β: 21803"
  },
  {
    "caption": "A NAD+ levels in  limb muscles of 20-month-old WT (n=7), mdx  (n=5) and mdx/CD38-/- (n=6) mice. Data information: Each dot of the graphs represents a mouse. in duplicate; After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "B CD38 expression: western blot  analysis of CD38 (B1) protein in  limb of WT and mdx mice (n=6 per group). Vinculin  is used as housekeeping protein control and the dot plots show the ratio of  CD38/vinculin.  qPCR analysis of CD38 mRNA (B2) in  limb of 20-month-old WT and mdx mice  (n=4 per group). Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: B1: unpaired Welch's t-test; B2 : unpaired Student's t-test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "C Histograms showing the  grip duration (latency to fall) (C1) and the limb force (C2) measured by a  grip test in WT (n=89), mdx (n=52, 53 respectively) and mdx/CD38-/- (n=58)  mice (age: 9 to 26 months old). Data information: C1 one value/mouse; C2 in triplicate. After normality and variance comparison tests, significance was assessed using: : unpaired Student's t-test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "D Images showing  muscle fiber  typology revealed by  immunostaining. Localization  of the slow MyHC (Type I) fiber  and fast  MyHCs (Type IIa  and IIb/X) fibers, along with  laminin (red) on transverse cross-sections from soleus and tibialis (TA) of WT, mdx  and mdx/CD38-/- mice. Scale bars: 100 µm. Histogram showing the percentage of I, IIa and IIb/X fiber type distribution in soleus  and TA of WT, mdx  and mdx/CD38-/- mice. Experiments performed in WT (n=3), mdx  (n=5) and mdx/CD38-/- (n=7)  mice for soleus; WT (n=5), mdx  (n=6) and mdx/CD38-/- (n=6) mice for TA. Data information: one value/mouse; After normality and variance comparison tests, significance was assessed using: D: Chi-square test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "E Fiber  size distribution in soleus from WT, mdx  and  mdx/CD38-/- mice. Data information: one value/mouse After normality and variance comparison tests, significance was assessed using: E: Kolmogorov-Smirnov test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "F Images displaying the collagen (blue) revealed by Masson's  trichrome staining in limb  of WT, mdx, and mdx/CD38-/- mice. The dot plot shows the quantification of collagen staining area (% total area) in limb of WT (n=4), mdx  (n=5) and mdx/CD38-/- (n=5)  mice. Scale bars: 200 µm. Data information: Each dot of the graphs represents a mouse. in triplicate. After normality and variance comparison tests, significance was assessed using: : ANOVA followed by Fisher's LSD test; Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "G Embryonic myosin expression  revealed by  immunostaining along with laminin  (green) on transverse cross-sections from limb of WT (n=5), mdx  (n=8) and  mdx/CD38-/- (n=8) mice. Scale bars: 50 µm. Dot plot showing the relative proportion of  embryonic myosin area in limb of WT, mdx  and mdx/CD38-/- mice. Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: G: Welch's ANOVA followed by Welch's t-tests. Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CD38: 12494"
  },
  {
    "caption": "B, New-born double knockout utrophin-dystrophin (mdx/utr-/-) mice and treatment with an  CD38  inhibitor. Mdx/utr-/- mice were subcutaneously injected with  K-rhein (0.6 and 2.5 mg/kg/d) for 4 weeks. B: Dot plots showing the treadmill performances of K-rhein-treated  mdx/utr-/- mice: distance traveled (B1), maximum speed reached (B2) and maximum running time (B3) (WT (NaCl) and mdx/utr-/-+ K-rhein 2.5 mg/kg/d n=10 mice per group; mdx/utr-/-(NaCl) and mdx/utr-/-+ K-rhein 0.6 mg/kg/d, n=12 mice per group). Data information: Each dot of the graphs represents a mouse. one value/mouse; After normality and variance comparison tests, significance was assessed using: ANOVA followed by Fisher's LSD test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001, #: p<0.001 vs mdx/utr-/- .",
    "ncbi_link": "dystrophin: 13405
utr: 22288
utrophin: 22288"
  },
  {
    "caption": "C New-born double knockout utrophin-dystrophin  (mdx/utr-/-) mice and treatment with an CD38 inhibitor. Mdx/utr-/- mice were subcutaneously injected with K-rhein  (0.6 and 2.5 mg/kg/d) for 4 weeks. C: Measurement of the grip duration (grid test) in WT (n=10), mdx/utr-/- (n=8) and K-rhein-treated mdx/utr-/- mice (n=10, 6 mice, respectively for the 0.6 mg/kg/d and 2.5 mg/kg/d doses). Data information: Each dot of the graphs represents a mouse. in triplicate. After normality and variance comparison tests, significance was assessed using: : Kruskal-Wallis followed by Dunn's test Values are expressed as means ± SEM. Significance: *p<0.05, **p<0.01, ***p<0.001, #: p<0.001 vs mdx/utr-/- .",
    "ncbi_link": "dystrophin: 13405
utr: 22288
utrophin: 22288"
  },
  {
    "caption": "A Mitochondrial translation products were labeled using a FUNCAT approach and [35S]Met labeling in control and TSFM patient fibroblasts. Representative epifluorescent microscopy and the autoradiography images are shown. Scale bars, 50 µm. Changes in mitochondrial protein synthesis were quantified for both approaches. For microscopy image analysis, >300 cells from N = 3 independent experiments were analyzed for each cell type. Mann-Whitney U test, ****p < 0.0001. For radiolabeling analyses, N =3 independent samples were quantified for each cell type. Student t test, **p < 0.01. Error bars, +/- SEM. B As in A using control and COA6 KO HEK cells. Scale bars, 25 µm. For microscopy image analysis, ****p < 0.0001, and for radiolabeling experiments, *p < 0.05 were calculated. Error bars, +/- SEM.",
    "ncbi_link": "COA6: 388753
TSFM: 10102"
  },
  {
    "caption": "(b) Temperature-sensitive growth assay. Yeast strains (wild-type or deletion mutants, indicated on the left) were transformed with either an empty vector or a plasmid carrying an artificial guide RNA gene targeting U2 pseudouridylation at position 42 and 44 (indicated on the top), and grown at various temperatures (indicated at the bottom).",
    "ncbi_link": "U2: RF00004"
  },
  {
    "caption": "(c) Blockage of pseudouridylation by deletion of specific pseudouridylase genes. RNAs isolated from wild-type and pseudouridylase-deletion strains (indicated on the top) were used for U2 pseudouridylation assay (CMC modification followed by primer-extension). Primer-extension pauses/stops correspond to ψ sites (indicated on the left and right). Note: The above-background signal of ψ42 in the snr81Δ lane (and to some extent, in the snr81Δ pus7Δ lane) is likely caused by the presence of strong ψ44 band. This is a primer-extension artifact, which often occurs when there is a strong ψ signal in the neighboring position. Alternatively, it is possible that having ψ at position 44 allows for an unidentified enzyme other than snR81 to modify U42 (albeit inefficiently) (Perhaps Pus1, which is responsible for ψ44 formation, can be a bit \"processive\"). Lanes 1-8 and lanes 9-16 are from two separate gels.",
    "ncbi_link": "Pus1: 855889
pus7: 854417
snr81: 9164973
snR81: 9164973
U2: RF00004
U42: RF00004"
  },
  {
    "caption": "(d) Restoration of U2 pseudouridylation by an artificial box H/ACA RNA. RNAs isolated from various yeast strains (indicated on the top), including the snr81Δ pusΔ strain that was transformed with an artificial guide RNA targeting positions 42 and 44 (lanes 9 and 10), were assayed for pseudouridylation [see legend to (c)].",
    "ncbi_link": "snr81: 9164973
U2: RF00004"
  },
  {
    "caption": "(a) Growth assay using the ACT1-CUP1 reporter system. Yeast cells carrying the ACT1-CUP1 reporter were deleted of pseudouridylase genes (indicated on the left), and were then assayed for growth at 30°C on media containing various concentrations of [Cu2+] (indicated at the bottom).",
    "ncbi_link": "ACT1: 
CUP1: "
  },
  {
    "caption": "(b) Growth rescue by restoration of pseudouridylation. The wild-type strain [from (a)] or the snr81Δ pusΔ strain [also from (a)], which exhibited the most severe growth-deficiency phenotype, was transformed with an empty vector or a plasmid carrying a pseudouridylation guide RNA gene targeting either position 42, position 44, or both (indicated). The resulting cells were assayed for growth at 30°C on media containing various concentrations of [Cu2+] (indicated at the bottom).",
    "ncbi_link": "snr81: 9164973"
  },
  {
    "caption": "(d) Splicing assay using the wild-type and mutant ACT1-CUP1 reporters. RNAs isolated from the wild-type and the snr81Δ pusΔ strains (indicated on the top), which carry the wild-type ACT1-CUP1 reporter pre-mRNA or any of the mutant ACT1-CUP1 reporter pre-mRNAs [indicated, also see (c)], were used for splicing assay (primer-extension analysis). The un-spliced pre-mRNA, lariat intermediate, and spliced mRNA are indicated. A primer complementary to U6 was also used (as an internal control) in the assay, and the U6 band is indicated as well. In addition, the growth phenotype of each strain (in various concentrations of [Cu2+]) is also shown. Lanes 1-12, lanes 13 and 14, and lanes 15 and 16 are from separate gels.",
    "ncbi_link": "ACT1: 
CUP1: 
snr81: 9164973
U6: RF00026"
  },
  {
    "caption": "(e) Quantification of ACT1-CUP1 mRNA levels. Spliced ACT1-CUP1 mRNA levels were calculated relative to U6 in each lane. The quantification was based on three independent experiments.",
    "ncbi_link": "ACT1: 
CUP1: 
U6: RF00026"
  },
  {
    "caption": "(f) Relative improvement/reduction for the mutant reporters. Relative improvement or reduction in splicing was calculated by normalizing the splicing efficiency (mRNA/U6) of each mutant reporter to that of WT reporter (set at 1).",
    "ncbi_link": "U6: RF00026"
  },
  {
    "caption": "Figure 3. Synthetic lethality assay. The Prp5 domain structure, and the mutations in some of the domains (indicated) are schematized at the top. Each of these PRP5 genes (wild-type or mutants, plasmid-borne) was used to replace the chromosomal PRP5. The numbers in parentheses are the relative ATPase activities of the wild-type (SAT) Prp5 and some of the Prp5 mutants tested before (Xu & Query, 2007). The U2 status, either containing Ψ42 and Ψ44 (WT-U2 and snR81Δ pus1Δ with pΨ42 or Ψ44) or lacking Ψ42 and Ψ44 (snR81Δ pus1Δ), is indicated (on the right). Upon transformation with the plasmids carrying PRP5 genes (wild-type or any of the mutants), cells were grown on the regular medium (-FOA) or on medium containing 5-FOA (+FOA).",
    "ncbi_link": "Prp5: 852539
PRP5: 852539
pus1: 855889
snR81: 9164973
U2: RF00004"
  },
  {
    "caption": "(a) Prp5-U2 co-immunoprecipitation (IP). Wild-type (lanes 1 and 2) and snR81Δ pus1Δ (lane 3) strains, each containing a FLAG-tagged PRP5 gene (indicated on the top), were used for anti-FLAG IP in the absence (lane 1) or presence (lanes 2 and 3) of ATP. The precipitated Prp5 (WT Prp5-FLAG) as well as co-precipitated U1 and U2, detected by primer-extension, are indicated.",
    "ncbi_link": "Prp5: 852539
PRP5: 852539
pus1: 855889
snR81: 9164973
U1: RF00003
U2: RF00004"
  },
  {
    "caption": "(b) Quantification of co-precipitated U2 snRNA. For each lane [the WT lane and the snr81Δ pus1Δ lane, corresponding to lane 2 and lane 3 of (a), respectively], Prp5-co-precipitated U2 was normalized against co-precipitated U1 [(intensity of the U2 band) / (intensity of the U1 band)]. The snr81Δ pus1Δ lane was then further normalized against the WT lane [(the value of normalized U2 from the snr81Δ pus1Δ lane) / (the value of normalized U2 from the WT lane)]. Quantification was based on three independent experiments.",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snr81: 9164973
U1: RF00003
U2: RF00004"
  },
  {
    "caption": "(c) U2 expression level in wild-type and snR81Δ pus1Δ strains. Total RNA, isolated from the wild-type (lane 1) or snR81Δ pus1Δ (lane 2) strains, was used for primer-extension to measure the levels of U2 and U6. The U2 and U6 bands are indicated.",
    "ncbi_link": "pus1: 855889
snR81: 9164973
U2: RF00004
U6: RF00026"
  },
  {
    "caption": "d) Depletion of Prp5. Wild-type (lanes 1, 3 and 4) and snR81Δ pus1Δ (lanes 2 and 5) cells containing a FLAG-tagged PRP5 were lysed, and anti-FLAG IP was performed at a high concentration of salt. Cell extracts, before (lanes 1 and 2), and after [lanes 3 (mock), 4 and 5] anti-FLAG IP, were used for western analysis using anti-FLAG. The Prp5 band is indicated.",
    "ncbi_link": "Prp5: 852539
PRP5: 852539
pus1: 855889
snR81: 9164973"
  },
  {
    "caption": "(e) IP of reconstituted Prp5 (GAR)-U2. An equal amount of FLAG-tagged Prp5 (GAR) was added to the wild-type (lane 1) and snR81Δ pus1Δ (lane 2) cell extracts depleted of endogenous Prp5 [see (c)]. After the salt concentration was brought back to its original level, anti-FLAG IP was carried out. The Prp5 (GAR) band, detected by western, is indicated. The co-precipitated U1 and U2 bands, detected by primer-extension, are also indicated.",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snR81: 9164973"
  },
  {
    "caption": "f) Quantification of U2 that is co-precipitated with mutant Prp5 (GAR). For each lane [including the WT lane and the snr81Δ pus1Δ lane, corresponding to lane 1 and lane 2 of (e), respectively], U2 co-precipitated with Prp5 (GAR) was normalized against co-precipitated U1 [(intensity of the U2 band) / (intensity of the U1 band)]. The snr81Δ pus1Δ lane was then further normalized against the WT lane [(the value of normalized U2 from the snr81Δ pus1Δ lane) / (the value of normalized U2 from the WT lane)]. Quantification was based on three independent experiments.",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snr81: 9164973
U1: RF00003
U2: RF00004"
  },
  {
    "caption": "(g) Prp5-U2-pre-mRNA co-IP. Reconstitution was carried out as described in (d). Prior to IP, an equal amount of radiolabeled pre-mRNA was also added to each reaction. Anti-FLAG IP was then performed in the presence of ATP. The precipitated Prp5 (WT and GAR) band, detected by western, is indicated. The co-precipitated pre-mRNA, directly visualized after electrophoresis, is also indicated. The pre-mRNA input is also shown. In lanes 1 and 2, wild-type and snR81Δ pus1Δ cell extracts, depleted of Prp5, were reconstituted with the wild-type FLAG-Prp5. In lanes 3 and 4, wild-type and snR81Δ pus1Δ cell extracts, depleted of Prp5, were reconstituted with mutant FLAG-Prp5 (GAR).",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snR81: 9164973"
  },
  {
    "caption": "(h) Quantification of pre-mRNA co-precipitated with Prp5 and U2. For each lane in (g), pre-mRNA co-precipitated with Prp5 (Wild-type or GAR) was normalized against the Prp5 (WT/GAR) band in the same lane (detected by Anti-FLAG) [(intensity of pre-mRNA) / (intensity of WT/GAR Prp5)]. Lanes 2,3,and 4 (see (g)) were then further normalized against lane 1 (see (g)) [(the value of normalized pre-mRNA from lane 2, 3 or 4 in (g)) / (the value of normalized pre-mRNA from lane 1 in (g))]. The numbers at the bottom of (h) correspond to the lane numbers of (g). Quantification was based on three independent experiments.",
    "ncbi_link": "Prp5: 852539"
  },
  {
    "caption": "(a) Prp5's ATPase activity assay using synthetic U2. The 5' sequence of S. cerevisiae U2 is shown (top). The three ψs (35, 42 and 44) as well as the branch site recognition sequence (underlined) are indicated. In the ATPase assay (bottom), no RNA (lane 3), or an equal amount of LiCl-precipitated RNA (lane 1) or tRNA (lane 2), a short U2 fragment (nts 1-76) (lane 4), a fully pseudouridylated short U2 fragment (nts 1-76) (lane 5), a long U2 fragment (nts 1-120) (lane 6), or a fully pseudouridylated long U2 fragment (nts 1-120) (lane 7), was used. The un-hydrolyzed ATP and hydrolyzed product ADP are indicated. Lanes 1 and 2, lanes 3-5, and lanes 6 and 7 are from separate gels.",
    "ncbi_link": "Prp5: 852539
U2: RF00004"
  },
  {
    "caption": "(b) Quantification of Prp5's ATPase activity activated by in vitro transcribed U2. Prp5's ATPase activity shown in (a) was calculated using the formula (ADP) / (ADT+ATP). The numbers at the bottom of (b) correspond to the lane numbers of (a). Quantification was based on three independent experiments.",
    "ncbi_link": "Prp5: 852539
U2: RF00004"
  },
  {
    "caption": "(c) U2-Prp5 binding assay. FLAG-Prp5 and a radiolabeled short (nts 1-76) (lanes 1 and 2) or long (nts 1-120) (lanes 5 and 6) U2 fragment, or FLAG-Prp5 and a radiolabeled fully pseudouridylated short (nts 1-76) (lanes 3 and 4) or long (nts 1-120) (lanes 7 and 8) U2 fragment, were incubated under the conditions used for ATPase activity assay. Anti-FLAG IP was then carried out. Co-precipitated (lanes 2, 4, 6 and 8) and un-precipitated (lanes 1, 3, 5 and 7) U2 RNAs were analyzed by electrophoresis. The U2 band is indicated.",
    "ncbi_link": "Prp5: 852539
U2: RF00004"
  },
  {
    "caption": "(d) Quantification of Prp5-U2 binding. Relative intensities of U2 bands shown in (c) were calculated [setting the un-precipitated uridine-containing U2 (lane 1 and 5) to 1]. The numbers at the bottom of (d) correspond to the lane numbers of (c). Quantification was based on three independent experiments.",
    "ncbi_link": "Prp5: 852539
U2: RF00004"
  },
  {
    "caption": "(e) Prp5's ATPase activity assay using cellular U2. U2 RNA isolated from the wild-type strain (lanes 2 and 4) or from the snR81Δ pus1Δ strain (lanes 6 and 8) was used for the ATPase activity assay. In odd-numbered lanes, no RNA was added. Both the wild-type Prp5 (lanes 1-4) and the mutant Prp5 (GAR) (lanes 5-8) were tested.",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snR81: 9164973
U2: RF00004"
  },
  {
    "caption": "(f) Quantification of Prp5's ATPase activity activated by U2 from cells. Prp5's ATPase activity shown in (e) was calculated using the formula (ADP) / (ADT+ATP). The numbers at the bottom of (f) correspond to the lane numbers of (e). Quantification was based on four independent experiments.",
    "ncbi_link": "Prp5: 852539
U2: RF00004"
  },
  {
    "caption": "(g) U2 level in the ATPase activity reactions. RNAs from lanes 2 and 4 in (c) were recovered, and U2 level was measured using primer-extension. Lanes 1-5, a titration of U2 snRNA. Lane 6, U2 from the wild-type strain [lane 2 of (c)]. Lane 7, U2 from the snR81Δ pus1Δ strain [lane 4 of (c)].",
    "ncbi_link": "pus1: 855889
snR81: 9164973
U2: RF00004"
  },
  {
    "caption": "(a) Native gel analysis of pre-splicing complexes. Pre-splicing complex assembly was carried out in the test tube with Prp5-reconstituted cell extracts and labeled pre-mRNA. Lane 1, Prp5-depleted wild-type cell extract. Lane 2, Prp5-depleted wild-type cell extract, plus wild-type Prp5. Lane 3, Prp5-depleted snR81Δ pus1Δ cell extract, plus wild-type Prp5. Lane 4, Prp5-depleted wild-type cell extract, plus mutant Prp5 (GAR). Lane 5, Prp5-depleted snR81Δ pus1Δ cell extract, plus mutant Prp5 (GAR). The pre-splicing complexes A and B are indicated.",
    "ncbi_link": "Prp5: 852539
pus1: 855889
snR81: 9164973"
  },
  {
    "caption": "(b) DMS in vivo probing. After being exposed to DMS, yeast cells were lysed, total RNA collected, and primer-extension analysis carried out (left panel). Lane 1, cells that were not exposed to DMS. Lane 2, wild-type cells exposed to DMS. Lane 3, snR81Δ pus1Δ cells exposed to DMS. Lane 4, snR81Δ pus1Δ cells, transformed with a plasmid carrying an artificial guide RNA gene targeting positions 42 and 44, and exposed to DMS. Lane 5, snR81Δ pus1Δ cells, transformed with a plasmid carrying a control guide RNA gene with random guide sequences, and exposed to DMS. The nucleotides in parentheses are DMS-modified C and A residues that are one nucleotide after the actual primer-extension stops (indicated by the arrows). A partial U2 sequence (along with the BSL structure) is shown (right panel). DMS-modified adenosine and cytosine in the BSL are also indicated.",
    "ncbi_link": "pus1: 855889
snR81: 9164973
U2: RF00004"
  },
  {
    "caption": "Immunofluorescence microscopy detection of Tmem117  in the mouse hypothalamus  and pituitary: (A, B) Positive immunostaining  was observed in the PVN, the SON  and the posterior pituitary. (C, D) No immunostaining  was detected in the hypothalamus  and pituitary  of mice  with constitutive inactivation of Tmem117  in AVP neurons. Data information: 3V: 3rd ventricle, AP: Anterior pituitary, MZ:  Medial zone, opt: optic tract, PP: Posterior pituitary, PVN: Paraventricular nucleus, SCh: Suprachiasmatic nucleus, SON: Supraoptic nucleus. Scale bar=100μm for panels",
    "ncbi_link": "Tmem117: 320709"
  },
  {
    "caption": "(H) Tmem117  mRNA levels in the PVN  [n=4 mice  per group]. (I)Tmem117  mRNA levels in the SON  [n=4 mice  per group Data information: INS: insulin, PVN: Paraventricular nucleus, SAL: saline, SON: Supraoptic nucleus. Lines correspond to the mean value per group and error bars represent ± SEM. Unpaired t-test; ns: p>0.05, *p<0.05, **p<0.01.",
    "ncbi_link": "Tmem117: 320709"
  },
  {
    "caption": "(B)  C-Fos expression  in the SON  Data information: AVP: Vasopressin INS: insulin opt: optic tract, SAL: saline, Scale bar=100μm.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998"
  },
  {
    "caption": "(G) Membrane potential  was increased comparably in response to 0.1 mM glucose  in both groups [n=7-9 cells per group]. (H) No change in  membrane potential in NR neurons  of both genotypes [n=9 cells per group]. (I) Membrane resistance  was decreased in 6 out of 9 AVPTM117WT and 6 out of 7 AVPTM117KO cells in response to 0.1 mM glucose  [n=7-9 cells per group]. (J) Membrane resistance in NR neurons  was stable for both genotypes [n=9 cells per group]. Data information: AVP: Vasopressin, d: day, GI: glucose  inhibited, NR: non-responding, Lines correspond to the mean value per group and error bars represent ± SEM. G-J: paired t-test for all graphs except Δ membrane potential (unpaired); nsp>0.05, *p<0.05, ***p>0.001.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998
TM117: 320709"
  },
  {
    "caption": "(A) Quantification of BiP  mRNA per cell in AVP-positive cells of the SON  [n=483-704 cells per group; each group consisted of 4 mice]. (B) Quantification of BiP  mRNA per cell in AVP-negative cells of the SON  [n=347-584 cells per group; each group consisted of 4 mice]. Data information: AVP: Vasopressin  For the violin plots dashed lines correspond to the median value and dotted lines to the quartile values. unpaired t-test ; *p<0.05, ***p>0.001.",
    "ncbi_link": "BiP: 14828"
  },
  {
    "caption": "(C) Fluorescence microscopy  detection of AVP  mRNA (green) and BiP  mRNA (magenta) in the SON. Data information: AVP: Vasopressin opt: optic tract  Scale bar=20μm.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998
BiP: 14828"
  },
  {
    "caption": "(F) Fluorescence microscopy  detection of DHE-derived fluorescence (red) in the SON. (G) Quantification of DHE-derived fluorescence in the SON  [n=8 SON  per group; each group consisted of 4 mice]. Data information: AVP: Vasopressin, d: day, DHE: dihydroethidium  , opt: optic tract, SON: Supraoptic nucleus,. Scale bar=20μm. For panels G data are represented as mean ± SEM. G: unpaired t-test; ; *p<0.05, ***p>0.001.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998"
  },
  {
    "caption": "(J) Calcium  recordings in AVP magnocellular terminals 10 minutes before and one hour after the i.p injection of insulin  (red and orange) or saline  (black). The vertical arrow corresponds to the i.p. injection (time=0). (K) Quantification of mean signal intensity in 10-minute time  bins. [n=6-8 mice  per group]. Data information: AUC: area under the curve, AVP: Vasopressin INS: insulin, SAL: saline  For panels K, data are represented as mean ± SEM. K: 1-way ANOVA with Tukey's post-hoc test; *p<0.05, ***p>0.001.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998"
  },
  {
    "caption": "(B) Immunofluorescence microscopy  detection of AVP  in the PVN  and the SON. Data information: 3V: 3rd ventricle, AVP: Vasopressin, KO: AVPTM117KO opt: optic tract, PVN: paraventricular nucleus, SON: Supraoptic nucleus, WT: AVPTM117WT. Scale bar=100μm.",
    "ncbi_link": "AVP: 11998
TM117: 320709"
  },
  {
    "caption": "(C) Quantitation of AVP  positive cells in the PVN  [n=3-4 mice  per group]. (D) Quantitation of AVP  positive cells in the SON [n=3-4 mice  per group]. Data information: AVP: Vasopressin, KO: AVPTM117KO WT: AVPTM117WT. For panels C and D lines correspond to the mean value per group and error bars represent ± SEM. For panels C,D: unpaired t-test; ; *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "AVP: 11998
TM117: 320709"
  },
  {
    "caption": "(E) Glycemia  one hour after saline  (black) or insulin  (red) i.p. injections in AVPTM117WT and AVPTM117KO male mice  [n=8-9 mice  per group]. (F) CPP plasma  levels one hour after saline  or insulin  injection in AVPTM117WT and AVPTM117KO male mice  [n=8 mice  per group]. (G) GCG plasma  levels one hour after saline  or insulin  injection in AVPTM117WT and AVPTM117KO male mice  [n=8-9 mice  per group]. Data information: AVP: Vasopressin, d: day, INS: insulin, KO: AVPTM117KO, SAL: saline, WT: AVPTM117WT. For panels E-G bars correspond to the mean value per group and error bars represent ± SEM. E-G: 2-way ANOVA for each timepoint in comparison to SAL  baseline with Bonferroni post-hoc test; *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "AVP: 11998
Vasopressin: 11998
TM117: 320709"
  },
  {
    "caption": "Green line: Normalized population expression level averaged over all OxyR, and SoxS-regulated promoters; red line: average over all LexA-regulated promoters as measured with a promoter-GFP plasmid library in a plate reader. Oxidative stress promoters clearly precede SOS response promoters in response to NIT stress, when measured at the population level Error bars show standard deviation over all detected oxidative stress and SOS promoters, respectively It is not clear if this temporal order correctly reflects the temporal order in single cells. B. Schematic showing response of two different genes (green and red) in three different cells (solid, dashed, dotted line). The temporal order observed at the population level correctly reflects the temporal order in each individual cell. C. As B. Here the temporal order at the population level is not the same in every single cell: Although in most cells, the green gene responds before the red one, one cell expresses the green gene before the red one (dashed lines).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Single-cell gene expression time traces from the dnaK promoter in response to TET stress, normalized to the median full response. Response times were determined as the time point at which a threshold expression level was reached This threshold was low enough so that most cells exceed it and high enough to avoid false positives due to the low signal-to-noise ratio at time point zero. Brown line: median of all cells. Time traces are from one microcolony. B. Histogram of the response times for the dnaK promoter with mean µt = 1.87 h and standard deviation σt = 0.37 h, and fit of an Erlang distribution with shape parameter n = 37 Response times are from two microcolonies.",
    "ncbi_link": "dnaK: 944750"
  },
  {
    "caption": "C. Standard deviation σt versus mean response time µt for 23 different promoters in three antibiotic stress conditions (TMP, TET, and NIT). The standard deviation of the response time σt grows with the mean response time µt and does not fall below a 'precision limit' (dashed line) that increases linearly with a slope ~0.165. The dotted line indicates the upper bound to timing variability where σt = µt, see text. The promoter dnaK under TET has low timing variability, whereas the promoters recA, fpr, osmC, and wrbA under TMP stress have high timing variability. The response time mean and standard deviation are from subsampling of descendants of single cells that were present at the time of stress addition Subsampling for each promoter was done from at least 2 microcolonies and the descendants of at least 17 individual cells present at the time of stress addition.",
    "ncbi_link": "dnaK: 944750
fpr: 948414
osmC: 946043
recA: 947170
wrbA: 947263"
  },
  {
    "caption": "E. Standard deviation σt versus mean response time µt for the LlacO-1 promoter induced with different IPTG concentrations.",
    "ncbi_link": "LlacO-1: "
  },
  {
    "caption": "D. Response times of the LlacO-1 promoter (Lutz & Bujard, 1997), induced with 1 mM IPTG at time zero, measured with YFP and CFP constructs in the same cell (r = 0.81 ± 0.04, p = 6 · 10-12).",
    "ncbi_link": "LlacO-1: 
CFP: 
YFP: "
  },
  {
    "caption": "A. Normalized expression from the promoters ybjC and recA in response to NIT stress, measured at the population level using GFP reporters 4 μg/mL NIT was added at time zero. The oxidative stress promoter ybjC clearly precedes the SOS response promoter recA, when measured at the population level Error bars show standard deviation of three replicate experiments measured on different days. B. Normalized ybjC and recA expression over time in response to the addition of 4 μg/mL NIT at time zero in single cells from one microcolony. Dashed line: threshold used to determine response times Lower panels, upper row: Dual-color images of the oxidative stress reporter ybjC (green) and the SOS reporter recA (red) in single cells at 4 different time points after NIT addition in one microcolony. Note that the ybjC signal (green) is stronger at t = 2h, whereas the recA signal (red) is only apparent at t = 4h and 6h. Lower row: Constitutively expressed mCherry used for segmentation. C. Response times for ybjC and recA from individual cells with dual reporters (Figure 3), combined from two microcolonies. All response times for recA are higher than for ybjC and response times for both reporters are strongly correlated (r = 0.74 ± 0.04, p = 3.8 · 10-6). The error of the correlation coefficient is from subsampling of descendants of single cells that were present at the time of NIT addition",
    "ncbi_link": "GFP: 
mCherry: 
recA: 947170
ybjC: 945481"
  },
  {
    "caption": "A. Expression from the gadB and recA promoters, measured at the population level using GFP reporters over time; 0.5 μg/mL TMP was added at time zero. The acid stress response (gadB) clearly precedes the SOS response (recA). Error bars show standard deviation of three replicate experiments measured on different days. B. Normalized expression of gadB and recA expression over time in individual cells responding to the addition of 0.5 μg/mL TMP at time zero shown for one microcolony. Dashed line: threshold used to determine response times (Methods). Lower panels, upper row: Dual-color images of gadB (blue) and recA (red) in single cells at 4 different time points. Most cells are predominantly either red or blue, i.e. acid stress and SOS response are typically not both strongly expressed in the same cells. Lower row: Constitutively expressed mCherry used for segmentation. C. Scatter plot of response times for gadB and recA in single cells; there is no clear temporal order and no significant correlation (r = 0.08 ± 0.08, p = 0.68); data is combined from three microcolonies. Error is from subsampling of descendants of single cells present at the time point of TMP addition",
    "ncbi_link": "GFP: 
mCherry: 
gadB: 946058
recA: 947170"
  },
  {
    "caption": "D. Expression of gadB and recA in inosine-supplemented medium, averaged over 13 single cells in a microcolony. Insets: Dual color image of gadB and recA and segmentation image at t = 6h.",
    "ncbi_link": "gadB: 946058
recA: 947170"
  },
  {
    "caption": "(A) Srcap expression in murine different tissues was examined by Northern blot. A 277 nt probe of Srcap (81-358nt) was labeled for Northern blot analysis. 18S RNA was used as a loading control.",
    "ncbi_link": "18S RNA: 
Srcap: 100043597"
  },
  {
    "caption": "(B) Two-week-old SRCAP-C-HA tag mice were sacrificed for longitudinal sections followed by immunofluorescence staining. A global look of the section was shown. Scale bar: 500 μm. Green: EpCAM, Red: HA tag, Nuclei were counterstained by DAPI.",
    "ncbi_link": "HA: 
SRCAP: 100043597"
  },
  {
    "caption": "(D) Duodenum region of intestinal tissues were obtained from Lgr5GFP-CreERT2 (Lgr5GFP) mice for immunofluorescence staining by indicated antibodies with OpalTM 7-color fIHC kit. Nuclei were counterstained with DAPI. Scale bar: 50 μm.",
    "ncbi_link": "GFP: 
Cre: 2777477
Lgr5: 14160"
  },
  {
    "caption": "(E) ISCs from Lgr5GFP mice were collected for organoid formation. Organoids were fixed for immunofluorescence staining with indicated antibodies. Scale bar: 50 μm. Data information: Green: EpCAM, Red: SRCAP, Purple: PCNA, Nuclei were counterstained by DAPI.",
    "ncbi_link": "GFP: 
Lgr5: 14160"
  },
  {
    "caption": "(A) Representative images of intestines from 8-week-old Srcap+/+ and Srcap-/- mice (n=6 per group). Length of 120 villi and 120 crypts (20 villi and 20 crypts per mouse) was measured and shown in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. Scale bar, 100 μm. Dotted lines indicate the boundary between crypts and villi. Arrows indicate the length of crypts or villi.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(B) Intestinal tissues from 8-week-old Srcap+/+ and Srcap-/- mice (n=6 per group) were collected for immunofluorescence staining with indicated antibodies. Typical images were shown in left panel and statistical ISC numbers from 120 crypts (20 crypts per mouse) were shown in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. Scale bar, 50 μm.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(D) Srcap+/+ and Srcap-/- mice were treated with 10 Gy's radiation and sacrificed at different time points. Intestinal tissues were collected for H&E staining. Numbers of intact crypts were shown in lower panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. 50 fields (10 fields per mouse) were taken for each group (n=5). Scale bars, 100 μm.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(E) Lgr5GFP-CreERT2;Rosa26lsl-YFP (LRYFP) were crossed with Srcapflox/flox mice, followed by administration of tamoxifen (TAM) for lineage tracing analysis. Mice were sacrificed 7 days after TAM induction and typical jejunum sections were stained. Numbers of traced crypt-villus units were shown in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. 50 fields (10 fields per mouse) were taken for each group (n=5). Scale bars, 50 μm.",
    "ncbi_link": "YFP: 
GFP: 
Cre: 2777477
Rosa26: 14910
Lgr5: 14160
Srcap: 100043597"
  },
  {
    "caption": "(F) Proliferation of Srcap+/+ and Srcap-/- ISCs were examined by Ki67 staining followed by flow cytometry analysis. Percentages of proliferated cells were counted as means ± S.D (lower panel). ** P < 0.01 by two-tailed Student's t-test. n=5 per group.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(G) Multiple color staining was performed in Srcap+/+ and Srcap-/- intestine sections. AP-Red, DAB and AP-Blue were used for immunohistochemistray coloration. Numbers of each kind of epithelial cells from 50 crypts or 50 villi (10 crypts and 10 villi per mouse) were shown in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. Scale bars, 50 μm.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(D) Flag-tagged REST fragments were expressed in 293T and purified by immunoprecipitation with anti-Flag antibody. REST proteins were incubated with crypt lysates for pulldown followed by immunoblotting.",
    "ncbi_link": "Flag: 
REST: 19712"
  },
  {
    "caption": "(B) Transcriptome microarray analysis between Srcap-/- ISCs and WT ISCs. Top ten downregulated TFs in Srcap-/- ISCs were listed.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(C) Prdm16 expression was tested in Srcap+/+ and Srcap-/- ISCs by Western blotting.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(E) Prdm16 promoter (-875~-854) region was used as probe to perform DNA-pulldown assay with murine intestinal crypt lysates followed by immunoblotting.",
    "ncbi_link": "Prdm16: 70673"
  },
  {
    "caption": "(F, G) Indicated promoter activation was analyzed with luciferase assay. DKK1 was used as a control. Results of relative fold changes are shown as means ± S.D. Data represent five independent replicates. . ** p<0.01 by two-tailed Student's t-test. .",
    "ncbi_link": "DKK1: "
  },
  {
    "caption": "(A) WT and Srcap-/- ISCs were conducted for transcriptome microarray, followed by Gene Set Enrichment Analysis (GSEA) analysis for PPARδ target genes.",
    "ncbi_link": "Srcap: 100043597"
  },
  {
    "caption": "(B) Expression levels of PPARs and PPAR target genes were assessed in sorted ISCs by quantitative RT-PCR. Primers were listed in Table EV1. Relative gene expression folds were normalized to endogenous β-actin and shown as means ± S.D. Data represent five independent replicates. ** p<0.01 and *** p<0.001 by two-tailed Student's t-test.",
    "ncbi_link": "β-actin: 11461"
  },
  {
    "caption": "(D) ISCs were collected for organoid formation followed by quantitative RT-PCR. For Prdm16 overexpression, ISCs were infected with lentivirus carrying Prdm16 overexpressing plasmids. Primers were listed in Table EV1. Relative gene expression folds were normalized to endogenous β-actin and shown as means ± S.D. Data represent five independent replicates. ** p<0.01 by two-tailed Student's t-test.",
    "ncbi_link": "β-actin: 11461
Prdm16: 70673"
  },
  {
    "caption": "(E) mRNA levels of ISC signature genes were examined by quantitative RT-PCR. Primers were listed in Table EV1. Relative gene expression folds were normalized to endogenous β-actin and shown as means ± S.D. Data represent five independent replicates.",
    "ncbi_link": "β-actin: 11461"
  },
  {
    "caption": "(A) Representative images of intestines from 8-week-old Rest+/+ and Rest-/- mice (n=6 per group). Length of 120 villi and 120 crypts (20 villi and 20 crypts per mouse) were measured in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. Scale bar, 100 μm. Dotted lines indicate the boundary between crypts and villi. Arrows indicate the length of crypts or villi.",
    "ncbi_link": "Rest: 19712"
  },
  {
    "caption": "(C) Intestine tissues from 8-week-old Rest+/+ and Rest-/- mice (n=6 per group) were collected for immunohistochemistry staining. Typical images were shown in left panel and statistical ISC numbers from 120 crypts (20 crypts per mouse) were shown in right panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. Scale bar, 50 μm.",
    "ncbi_link": "Rest: 19712"
  },
  {
    "caption": "(D) Immunofluorescence staining of intestine tissues from Srcapfl/fl; Lgr5GFP-CreERT2 and Restfl/fl; Lgr5GFP-CreERT2 mice. Scale bar, 50 μm.",
    "ncbi_link": "GFP: 
Cre: 2777477
Lgr5: 14160
Rest: 19712
Srcap: 100043597"
  },
  {
    "caption": "(E) Lgr5GFP-CreERT2;Rosa26lsl-lacZ (LRlacZ) were crossed with Rest-/- mice, followed by TAM administration for lineage tracing for intestinal whole-mount staining for β-gal (upper panel) . Mice were sacrificed after one week and typical sections were shown (middle panel). Scale bar, 200 μm. Numbers of traced crypt-villus units were calculated as means± S.D. ** P < 0.01 by two-tailed Student's t-test in right panel. 50 fields (10 fields per mouse) were calculated for each group (n=5) (lower panel).",
    "ncbi_link": "GFP: 
Cre: 2777477
Rosa26: 14910
lacZ: 945006
Lgr5: 14160
Rest: 19712"
  },
  {
    "caption": "(F) Rest+/+ and Rest-/- mice were treated with 10 Gy's radiation and sacrificed at the indicated time points. Intestinal tissues were collected for H&E staining. Scale bars, 100 μm. Numbers of intact crypts were shown in lower panel as means± S.D. ** P < 0.01 by two-tailed Student's t-test. 50 fields (10 fields per mouse) were taken for each group (n=5).",
    "ncbi_link": "Rest: 19712"
  },
  {
    "caption": "(G) Representative images of organoid formation from indicated ISCs were shown (upper panel). Scale bar, 200 μm. n=6 for each group. Organoid number per well was counted as means ± S.D. (lower panel). Lentivirus-carried sgPrdm16 and sgPpard were prepared in 293T cells and infected into ISCs derived from TAM-treated LRCas9 mice to obtain Prdm16-/- and Ppard-/- ISCs. 1×104 ISCs from indicated mice were collected for organoid formation. Scale bar, 200 μm. n=5 for each group.",
    "ncbi_link": "Cas9: 46806597
Ppard: 19015
Prdm16: 70673"
  },
  {
    "caption": "f, GFP-LC3-transfected macrophages were infected with wild-type or D actA bacteria. Where indicated, chloramphenicol (CM) was added to the media at 3 h post infection. The number of bacteria per SLAP was quantified. Brackets indicate significant differences, and corresponding P values are shown.",
    "ncbi_link": "actA: 987035"
  },
  {
    "caption": "a, GFP-LC3-transfected macrophages were infected for 4 h, and the percentage of infected cells exhibiting SLAPs was quantified. Mean ± s.e.m. for three independent experiments. P values for strains with significant differences from wild-type levels are shown.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "b, Macrophages were infected with IPTG-induced iLLO bacteria. Arrowheads indicate actin- iLLO bacteria within LAMP1+ vacuoles.",
    "ncbi_link": "LLO: 987033"
  },
  {
    "caption": "c, Macrophages were infected with wild-type (triangles) or IPTG-induced iLLO (circles) bacteria, and the percentage of LAMP1+ bacteria was quantified. Mean ± s.e.m. for three independent experiments.",
    "ncbi_link": "LLO: 987033"
  },
  {
    "caption": "d, Macrophages were infected as in c with or without IPTG induction. Intracellular bacterial replication was determined using a gentamicin-protection assay. Shown is fold replication compared to 2 h post infection. Clear triangles, wild type; filled triangles, wild type + IPTG; clear circles, iLLO; filled circles, iLLO + IPTG. Mean ± s.e.m. or range for three (wild type, wild type + IPTG, iLLO + IPTG) or two (iLLO-IPTG) independent experiments, respectively.",
    "ncbi_link": "LLO: 987033"
  },
  {
    "caption": "e, Wild-type or Atg5-/- MEFs were infected with iLLO bacteria, and intracellular bacterial replication was determined as in d. Mean ± s.e.m. for three independent experiments. Clear circles, wild-type MEFs; filled circles, wild-type MEFs + IPTG; clear squares, Atg5-/- MEFs; filled squares, Atg5-/- MEFs + IPTG.",
    "ncbi_link": "Atg5: 11793
LLO: 987033"
  },
  {
    "caption": "f, Wild-type (circles) or Atg5-/- (squares) MEFs were infected as in e with IPTG induction. The percentage of LAMP1+ bacteria was quantified as in c. Mean ± s.e.m. for three independent experiments. g",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) THP-1 cells were transiently infected with BRLF1-expressing or empty control lentivirus. Twenty-four hours later, the control or BRLF1-expressing THP-1 cells were primed with 40 ng/ml TPA overnight and then were either uninfected or infected with HSV-1 (MOI=1) in serum-free medium for 12 h. The supernatants and whole cell lysates were collected and analyzed by western blotting to detect pro-caspase-1 (p45), cleaved caspase-1 (p20), pro-IL-1β, mature IL-1β, pro-IL-18 and mature IL-18 as indicated.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "Ramos cells were infected with wild type EBV-WT or BRLF1-deficient EBV-ΔBRLF1 virus at a high titer (MOI=100). After being transduced with empty control or BZLF1-expressing lentivirus, the supernatants and cell pellets of EBV-WT- or EBV-ΔBRLF1-harboring Ramos cells were collected after 12 h in serum-free culture, and then the levels of EBNA1, BRLF1, BZLF1, pro-caspase-1 (p45), cleaved caspase-1 (p20), pro-IL-1β, mature IL-1β, pro-IL-18, mature IL-18, GSDMD and cleaved N-GSDMD in the supernatants and whole-cell lysates were analyzed as indicated (d).",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744"
  },
  {
    "caption": "(g) After being transduced with control or BZLF1-expressing lentivirus for 48 h, EBV-WT- and EBV-ΔBRLF1 infected Ramos cells were stained with PI and measured using fluorescent flow cytometry. Representative images of pyroptotic cells are shown and the percentages of pyroptotic cells were calculated in duplicate.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744"
  },
  {
    "caption": "(a) GST-tagged BRLF1-expressing plasmid or control vector was transfected into A549 cells. After HSV-1 infection (MOI=1) for 12 h, the cells were collected, and the whole cell extracts were subjected to immunoprecipitation with GST affinity beads. The immunoprecipitated complexes were then separated by SDS-PAGE, and the image obtained from silver staining is shown.",
    "ncbi_link": "GST: 
BRLF1: 3783727"
  },
  {
    "caption": "(b) Scramble (sc) or shRNAs against POLR3F and POLR3G with empty control vector (ctr) or BRLF1-expressing plasmid were transfected into EBV-ΔBRLF1-harboring HNE1 cells and A549 cells, followed by HSV-1 infection. Thirty-six hours after the transfection of the HNE1 cells, and 12 h after HSV-1 infection (MOI=1) of the A549 cells, the cell pellets were collected and then the cleavage of caspase-1 and IL-1β were measured as indicated. The release of mature IL-1β and IL-18 from HNE-1 and A549 cells were measured by enzyme-linked immunosorbent assay (ELISA) after ultrafiltration and concentration with Amicon® Ultra-0.5 centrifugal filter devices.",
    "ncbi_link": "BRLF1: 3783727
POLR3F: 10621
POLR3G: 10622"
  },
  {
    "caption": "(c) GFP-tagged BRLF1 wild type, BRLF1 L578A or empty vector was transfected into 293T cells with GST-tagged POLR3F or POLR3G expressing plasmids for 48 h. Cells were collected and immunoprecipitation with GST-affinity beads was performed, and then whole cell lysates and immunoprecipitated complexes were analyzed as indicated.",
    "ncbi_link": "GFP: 
BRLF1: 3783727
POLR3F: 10621
POLR3G: 10622"
  },
  {
    "caption": "(d) GFP-tagged empty vector or GFP-BRLF1- or GFP-BRLF1 L578A-expressing plasmids were transfected into A549 cells, after which the cells were then infected with HSV-1, or transfected into HNE-1-EBV-ΔBRLF1 cells. The cells were then collected and lysed. Immunoprecipitation with GST-affinity beads was subsequently performed, and then whole-cell lysates and immunoprecipitated complexes were analyzed as indicated.",
    "ncbi_link": "GFP: 
BRLF1: 3783727"
  },
  {
    "caption": "(a) After infected with wild type EBV-WT or BRLF1-deficient EBV-ΔBRLF1 virus at a high titer (MOI=100), POLR3-dependent RNA transcripts in Ramos cells were detected by RNA-seq analysis. The relative levels of cellular small RNA transcripts are shown as RNA fold changes in the heatmap in the mock (mock group vs. mock group), EBV-WT (EBV-WT group vs. mock group) and EBV-ΔBRLF1 (EBV-ΔBRLF1 group vs. mock group) comparisons.",
    "ncbi_link": "BRLF1: 3783727
POLR3: 10621///10622"
  },
  {
    "caption": "(b) EBV-ΔBRLF1-harboring HNE1 cells were transfected with control vector, BRLF1 or BRLF1 L578A in the absence or presence of BZLF1 for 48 h. The total RNAs were extracted and subjected to real-time PCR analysis.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744"
  },
  {
    "caption": "(c) A549 cells were transfected with control vector, BRLF1 or BRLF1 L578A for 36 h. After the cells were infected with HSV-1(MOI=1) for 12 h, the total RNAs were extracted and subjected to real-time PCR analysis.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "(d) EBER1 5'-pppRNA detection using splint-ligation. EBV-WT- or EBV-ΔBRLF1-harboring HNE1 cells were cotransfected with empty vector, BRLF1 or BRLF1 L578A, BRLF1 plus BZLF1, or BRLF1 L578A plus BZLF1 for 48 h. The total RNAs were extracted, and 5 μg of each RNA was subjected to splint-ligation with FAM-labeled probe to quantify the 5′-monophosphorylated EBER1 and total EBER1 RNA. The ligation products were separated using urea-PAGE, visualized by a fluorescent scanner and analyzed using ImageJ software. The ratio of 5'-pRNA density to total RNA density and the relative 5'-pppRNA level were calculated for three independent experiments.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744
EBER1: RF01789"
  },
  {
    "caption": "(e) EBV-WT-harboring HNE1 cells were transfected with control vector, BRLF1 or BRLF1 L578A-expressing plasmid in the presence of GST-tagged RNA polymerase subunit POLR3F for 48 h. The cells were harvested and ChIP assay was performed with anti-GST affinity beads. The POLR3F-binding promoter fragments of BSRF1, BMLF1, EBER1, EBER2, EBNA1, 7SK, RN7SL1 and the GAPDH as negative control in the ChIP samples were detected by real-time PCR assays.",
    "ncbi_link": "EBER2: 
EBNA1: 
GAPDH: 
GST: 
BRLF1: 3783727
BMLF1: 3783758
BSRF1: 3783731
EBER1: RF01789
POLR3F: 10621
7SK: 125050
RN7SL1: 6029"
  },
  {
    "caption": "(a) Stable 293T cells in the presence of pro-caspase-1, pro-IL-1β and ASC overexpression were transfected with control vector or BRLF1 with control vector, IFI16, NLRP3, RIG-I or AIM2 for 36 h. After the cells were infected with HSV-1 (MOI=1) for 12 h, the cells were collected, and the cell lysates were analyzed by western blotting to determine the levels of pro-caspase-1, cleaved caspase-1, pro-IL-1β and mature IL-1β as indicated.",
    "ncbi_link": "AIM2: 9447
BRLF1: 3783727
RIG-I: 23586
IFI16: 3428
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "(b) Scramble (sc) or shRNAs against RIG-I and empty control vector (ctr), BRLF1- or BRLF1 L578A-expressing plasmids were co-transfected into EBV-ΔBRLF1-harboring HNE1 cells. Thirty-six hours after the transfection, cell pellets were collected, after which the cleavage of caspase-1 and IL-1β was measured as indicated.",
    "ncbi_link": "BRLF1: 3783727
RIG-I: 23586"
  },
  {
    "caption": "(c) Analysis of ASC oligomerization. ASC-expressing plasmid was transfected into 293T cells or HNE1 cells with empty vector or GFP-BRLF1 in the presence of AIM2- or RIG-I-expressing plasmid. Twelve hours after HSV-1 infection (MOI=1) in 293T cells, or 48 h after EBV-ΔBRLF1 infection (MOI=1000) in HNE1 cells, the cell pellets were collected, and cell lysates were treated with DSS to induce chemical cross-linking and analyzed by western blotting for ASC oligomerization.",
    "ncbi_link": "GFP: 
AIM2: 9447
BRLF1: 3783727
RIG-I: 23586
ASC: 29108"
  },
  {
    "caption": "(d) EBV-ΔBRLF1-harboring HNE1 cells were transfected with control vector, BRLF1 or BRLF1 L578A in the absence or presence of BZLF1 for 48 h. The total RNAs were extracted and subjected to real-time PCR analysis.",
    "ncbi_link": "BRLF1: 3783727
BZLF1: 3783744"
  },
  {
    "caption": "(e) A549 cells were transfected with control vector, BRLF1 or BRLF1 L578A for 36 h. After the cells were infected with HSV-1 (MOI=1) for 12 h, the total RNAs were extracted and subjected to real-time PCR analysis.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "Jurkat cells (a) were infected with EBV-WT or EBV-ΔBRLF1 virus (MOI=500) for 36 h. Then, the cells were collected, and the total RNAs were extracted, reverse-transcribed and analyzed by real-time PCR. Color gradient depicts the mean mRNA expression normalized to the housekeeping gene GAPDH and compared to the mock group.",
    "ncbi_link": "GAPDH: 
BRLF1: 3783727"
  },
  {
    "caption": "NK-92MI cells (b) were infected with EBV-WT or EBV-ΔBRLF1 virus (MOI=500) for 36 h. Then, the cells were collected, and the total RNAs were extracted, reverse-transcribed and analyzed by real-time PCR. Color gradient depicts the mean mRNA expression normalized to the housekeeping gene GAPDH and compared to the mock group.",
    "ncbi_link": "GAPDH: 
BRLF1: 3783727"
  },
  {
    "caption": "Jurkat and NK-92MI cells were cultured with conditional medium from EBV-WT or EBV-ΔBRLF1-infected Ramos cells (paracrine), or Jurkat and NK-92MI cells were directly infected with EBV-WT or EBV-ΔBRLF1 viruses (autocrine). (c) The cell pellets were collected and the whole cell extracts were analyzed by western blotting to detect TAK1, IKKα/β and IκB phosphorylation.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "Anti-IL-1β and/or anti-IL-18 neutralizing antibodies (NA), TAT-Flag or TAT-N572 peptide were added into EBV-WT- or EBV-ΔBRLF1-infected Jurkat cells or NK-92MI cells for 24 h. (f) TAK1, IKKα and IκB phosphorylation were detected as indicated.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "(a-d) PBMCs were isolated and infected with EBV-WT or EBV-ΔBRLF1 virus (MOI=500). Thirty-six hours after infection, the cells were harvested and the total RNAs were extracted, reverse-transcribed and subjected to real-time PCR analysis. The differential expression of receptors and cytokines (a), cytotoxic genes (b), T cell-specific genes (c) and NK cell-specific genes (d) are shown. The values are shown as the mean ± standard deviations of five analyses of PBMCs from five different health donors.",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "(e-h) FACS analysis of T and NK cell activation in PBMCs in the presence of EBV-WT or EBV-ΔBRLF1 primary infection. The PBMCs were left uninfected or infected with EBV-WT or EBV-ΔBRLF1 virus for 36 h, and the EBV-ΔBRLF1-infected lymphocytes were incubated with additional TAT-Flag or TAT-N572 peptide for 12 h. Immunofluorescent PE-CD3 and APC-CD25 antibodies were used to detect T cell activation (e, g), and PE-CD56 and APC-CD69 were used to detect NK cell activation (f, h). Representative images of the FACS analysis of T cell and NK cell activation are shown (e, f), and the percentages of activated T cells and NK cells were calculated and are shown as the mean ± standard deviation (g, h) for lymphocytes from 5 different health donors;",
    "ncbi_link": "BRLF1: 3783727"
  },
  {
    "caption": "(a) Representative image of a Control (left) and Myo1cKO (right) embryo. Top: max projections of embryos stained with Phalloidin (green) and DAPI (gray). Bottom: magnifications at dashed rectangles of Phalloidin (grey) with white arrows pointing at fragments. Data information: Mann-Whitney test p values are indicated. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(b-c) Number of fragments without DNA (b) per embryo and mean radius (c) in Control (grey) and Myo1cKO (salmon) embryos (left, Control n = 20, Myo1cKO n = 20). Boxplot shows median, upper and lower quartiles, min and max values. Whisker plot shows median, upper and lower quartiles. Data information: Mann-Whitney test p values are indicated. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(d) Representative images of a time-lapse of Myo1cKO embryo undergoing fragmentation outside of division (top) and during division (bottom). Max projections of embryos expressing mTmG (grey) and mCherry-EB3 (grey) imaged with light sheet microscopy are shown. White arrows point at the forming fragments. (e) Ratio of fragmentation events during and outside of division (n = 13 cells from 7 embryos). Data information: Mann-Whitney test p values are indicated. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(a) Representative images of Control (left) and Myo1cKO (right) embryos expressing mTmG and mCherry-EB3 (grey) shown as max projections. White arrows point at the mitotic spindle. (b-c) Spindle persistence in Control (n = 6) and Myo1cKO (n = 9) embryos (b) and in non-fragmenting and fragmenting cells of Myo1cKO embryos (c, n = 42 and 12 cells from 7 Myo1cKO embryos). Spindle persistence measures the time from appearance to disassembly of the spindle. Data information: Mann-Whitney test p values are indicated. Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(d) Top: Representative images of a time-lapse of a Myo1cKO embryo expressing Myh9-GFP (green) and mTmG (magenta) while labelled with SiRDNA (grey) undergoing fragmentation during mitosis shown as max projections. Bottom: magnifications of Myh9-GFP (grey) at dashed rectangles showing cortical accumulation (middle) followed by fragmentation (right). Data information Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(e) Control (grey) and Myo1cKO (salmon) embryos Myh9-GFP Ic/Iref values at DNA-cortex distances < 20 µm and > 20 µm (Control embryos n = 10, cells n = 35; Myo1cKO embryos n = 9, cells n = 26) Data information: Kruskal-Wallis and pairwise Mann-Whitney tests (e) p values are indicated. Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(f) Comparison of the increase in Myh9-GFP intensity in Control and Myo1cKO embryos when DNA is in close proximity to the cortex. The ratio Ic0-20/Ic>20 is calculated from Myh9-GFP intensities at the contact region when DNA-cortex distances are < 20 µm (Ic0-20) divided by intensities when distances are > 20 µm (Ic>20) (Control embryos n = 10, cells n = 33; Myo1cKO n = 9, cells n = 26). Data information: Mann-Whitney test p values are indicated. Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(a) Representative images of Control (left) and Myo1cKO (right) embryos labelled with SiRDNA (grey) and expressing a reporter of Cdc42 activity (yellow) in one blastomere, which is undergoing mitosis, shown as max projections. The second blastomere is outlined with a dashed line. White arrows point at the accumulation of active Cdc42 at the cortex in close proximity to DNA. (b) The ratio of active Cdc42 Ic/Iref was compared between < 20 µm and > 20 µm DNA-cortex distances for Control (dark yellow) and Myo1cKO (yellow) embryos (Control embryos n = 10; Myo1cKO embryos n = 10). Data information: Kruskal-Wallis and pairwise Mann-Whitney tests (b Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Myo1c: 17913"
  },
  {
    "caption": "(c) Representative images of Myo1cKO embryos expressing LifeAct-GFP (green) alone (left) or together with dominant negative Cdc42 (DNCdc42, right) labelled with SiRDNA (grey) shown as max projections. White arrows point at the cortex in close proximity to DNA. (d) LifeAct-GFP Ic/Iref values at DNA-cortex distances < 20 µm and > 20 µm for Myo1cKO (salmon) and Myo1cKO + DNCdc42 (yellow) embryos (Myo1cKO embryos n = 8, cells n = 19; Myo1cKO + DNCdc42 embryos n = 12, cells n = 30). Data information: Kruskal-Wallis and pairwise Mann-Whitney tests d) Boxplots show median, upper and lower quartiles, min and max values. Scale bars, 10 µm.",
    "ncbi_link": "Cdc42: 
Myo1c: 17913"
  },
  {
    "caption": "F-M Compared with wild-types (F-I), mutants (J-M) completely lost the CM (red) in the gut of 7dpf larva (F, J), as well as in the intestinal bulb (G, K), middle intestine (H, L) and posterior intestine (I, M) of adults. Red, SNAP-CBD stain; blue, DAPI stain; WT, wild-type; MU, chs1-/- mutant.",
    "ncbi_link": "chs1: 322468"
  },
  {
    "caption": "B Comparison of 3-month-old wild-types and mutants in the pairwise microbiota compositional dissimilarity (Jaccard distance) between the digesta (niche1) and the epithelia (niche2). This metric represents the radial gradient of the gut bacterial composition. The comparison was done on four taxonomy levels. Data of n=14 individuals were represented in box (interquartile range) and whisker (min to max) plots. Individual data points were plotted as black dots. * P < 0.05, ** P < 0.01 by the conservative, nonparametric Kruskal-Wallis test. Please see Appendix Fig S10 for another way of data presentation, and Dataset EV1 for the details of the sample information and raw statistics. Note that each 16S-rRNA library contains only one sample from one animal.",
    "ncbi_link": "16S-rRNA: "
  },
  {
    "caption": "A Luciferase complementation imaging (LCI) assays showing that BIC1 interacts with BZR1. nLUC-BZR1 was co-transformed with cLUC-CCA1, cLUC-TOC1, cLUC-ELF3, cLUC-LUX, cLUC-BIC1, cLUC, respectively, in leaf epidermal cells of Nicotiana benthamiana as indicated.",
    "ncbi_link": "LUC: 
BIC1: 824440
BZR1: 843845
CCA1: 819296
ELF3: 817134
LUX: 823817
TOC1: 836259"
  },
  {
    "caption": "B BiFC assays showing the interaction of BIC1 and BZR1 mainly in nucleus. Leaf epidermal cells of Nicotiana benthamiana were co-transformed with nYFP-BZR1 and cYFP-BIC1. BF, bright field. Scale bars represent 20 μm.",
    "ncbi_link": "YFP: 
BIC1: 824440
BZR1: 843845"
  },
  {
    "caption": "A, B Hypocotyl elongation phenotypes of the BIC1 overexpression and mutant lines in response to BR treatment. Col-0, 35S:BIC1-YFP, 35S:BIC1-Flag and bic1bic2 seedlings were grown for 6 days on 1/2 MS medium supplemented with 1 μM brassinazole (BRZ) plus different concentrations of epibrassinolide (eBL). Images of the representative seedlings are shown in (A), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (B). Data are means ± SD; n>20. Scale bars, 2 mm.",
    "ncbi_link": "Flag: 
YFP: 
bic2: 823570
BIC1: 824440
bic1: 824440"
  },
  {
    "caption": "C RT-qPCR analysis of BZR1-activated gene expression in the bic1bic2 double mutants. The 6-d-old Col-0 and bic1bic2 seedlings grown on 1/2 MS medium supplemented with 1 μM BRZ were treated with 5 μM eBL (+eBL) or not (-eBL) for 1 hour. The PP2A gene served as internal control. Data are means ± SD (n=3).",
    "ncbi_link": "bic2: 823570
bic1: 824440
PP2A: 843333"
  },
  {
    "caption": "D Heat map of BIC1-regulated genes. The Col-0 and 35S:BIC1-YFP seedlings were grown on 1/2 MS medium for 10 days. Three biologic replicates were performed. The colored bar beneath the map indicates fold change (log2 value).",
    "ncbi_link": "YFP: 
BIC1: 824440"
  },
  {
    "caption": "E BIC1 facilitates the expression of cell elongation genes. RT-qPCR analysis of genes selected in transcriptomic data. The Col-0, 35S:BIC1-YFP and 35S:BIC1-Flag seedlings were grown for 5 days under long-day conditions. The PP2A gene served as internal control. Data are means ± SD (n=3).",
    "ncbi_link": "Flag: 
YFP: 
BIC1: 824440
PP2A: 843333"
  },
  {
    "caption": "A, B BIC1 and BZR1 synergistically promote hypocotyl elongation. The Col-0, 35S:BZR1-MYC, 35S:BIC1-YFP and 35S:BZR1-MYC/35S:BIC1-YFP plants were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (A), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (B). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "MYC: 
YFP: 
BIC1: 824440
BZR1: 843845"
  },
  {
    "caption": "C-E BR signaling is enhanced in the 35S:BZR1-MYC/35S:BIC1-YFP plants. Seedlings were grown for 6 days on medium supplemented with 1 μM brassinazole (BRZ) plus a gradient of concentrations of epibrassinolide (eBL) under long-day conditions. Images of the representative seedlings when grown with 500 nM eBL (+eBL) or not (-eBL) are shown in (C), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (D) and (E). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "MYC: 
YFP: 
BIC1: 824440
BZR1: 843845"
  },
  {
    "caption": "F, G BZR1-mediated hypocotyl elongation phenotype is dependent on the function of BIC1 and BIC2. Seedlings were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (F), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (G). Data are means ± SD (n>20). **p < 0.01, n.s. indicates no significant difference, (Student's t-test). Scale bar, 2 mm.",
    "ncbi_link": "BIC2: 823570
BIC1: 824440
BZR1: 843845"
  },
  {
    "caption": "H BZR1-mediated hypocotyl elongation phenotype is dependent on the function of BIC1 and BIC2. The Col-0, 35S:BZR1-MYC, bic1bic2, 35S:BZR1-MYC/bic1bic2 seedlings were grown on medium supplemented with 1 μM BRZ plus different concentrations of eBL for 6 days and then the hypocotyl lengths were measured. Data are means ± SD (n>20).",
    "ncbi_link": "MYC: 
bic2: 823570
bic1: 824440
BZR1: 843845"
  },
  {
    "caption": "A BR enhances the stability of BIC1 proteins. The 5-d-old 35S:BIC1-YFP transgenic plants were treated with 100 μM cycloheximide (CHX) or co-treated with 100 μM CHX and 1 μM epibrassinolide (eBL). Samples were collected at indicated time points and BIC1-YFP protein levels were analyzed by western blots using anti-GFP antibody. Actin was used to verify equal protein loadings. Intensity of the bands was measured using Adobe Photoshop CS3 Extended program. Three independent experiments were performed with similar results.",
    "ncbi_link": "YFP: 
BIC1: 824440"
  },
  {
    "caption": "C Transactivation analysis of BIC1 using a yeast assays. The GAL4 DNA-binding domain (BD) alone was used as the negative control. SD-W, synthetic dextrose medium lacking Trp; SD-WH, synthetic dextrose medium lacking both Trp and His.",
    "ncbi_link": "GAL4: 855828"
  },
  {
    "caption": "E Transient transcriptional activity analysis in Arabidopsis protoplasts illustrating the transcriptional activation activity of BIC1. The relative luciferase activities were calculated by normalizing the LUC values against REN. Error bars represent SD (n = 3). **p < 0.01, as determined by a Student's t-test.",
    "ncbi_link": "LUC: 
REN: 
BIC1: 824440"
  },
  {
    "caption": "G Transient expression assays in Arabidopsis protoplasts showing that BIC1 and BZR1 synergistically activate PRE5 promoter. The ProPRE5:LUC reporter was co-transformed with the indicated effector constructs. The LUC/REN ratio represents the ProPRE5:LUC activity relative to the internal control (REN driven by the 35S promoter). Error bars represent SD (n = 3).",
    "ncbi_link": "LUC: 
REN: 
BIC1: 824440
BZR1: 843845
PRE5: 2745895"
  },
  {
    "caption": "H, I BIC1-mediated hypocotyl elongation was reduced by the addition of SRDX motif. Seedlings were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (H), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (I). #1, #2, #3 represent different 35S:BIC1-SRDX-Flag transgenic lines. Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "Flag: 
BIC1: 824440"
  },
  {
    "caption": "LCI assays showing that BIC1 interacts with PIF4. Leaf epidermal cells of Nicotiana benthamiana were co-transformed with nLUC-BIC1 or nLUC and cLUC-PIF4 or cLUC as indicated.",
    "ncbi_link": "LUC: 
BIC1: 824440
PIF4: 818903"
  },
  {
    "caption": "C Co-IP assays showing the interaction between BIC1 and PIF4 in vivo. The 35S:BIC1-YFP, 35S:PIF4-MYC and 35S:PIF4-MYC/35S:BIC1-YFP transgenic plants were grown for 6 days under long-day conditions. The immunoprecipitates were detected using anti-GFP and anti-MYC antibodies, respectively.",
    "ncbi_link": "MYC: 
YFP: 
BIC1: 824440
PIF4: 818903"
  },
  {
    "caption": "D, E Phenotypic analyses showing that BIC1 and PIF4 synergistically promote hypocotyl elongation. The Col-0, 35S:BIC1-YFP, 35S:PIF4-MYC and 35S:PIF4-MYC/35S:BIC1-YFP plants were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (D), and the hypocotyl lengths of the indicated genotypes were measured and are shown in (E). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "MYC: 
YFP: 
BIC1: 824440
PIF4: 818903"
  },
  {
    "caption": "F RT-qPCR analysis showing that BIC1 and PIF4 synergistically activate PIF4 target genes. The seedlings growth conditions were same as (D). The PP2A gene was used as an internal control. Data are means ± SD (n=3).",
    "ncbi_link": "BIC1: 824440
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "G,H Phenotypic analyses showing that PIF4-induced hypocotyl elongation is partially. dependent on the function of BIC1 and BIC2. The Col-0, bic1bic2, PIF4-MYC and PIF4-MYC/bic1bic2 plants were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (G) and the hypocotyl lengths of indicated genotypes were measured and are shown in (H). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "MYC: 
bic2: 823570
bic1: 824440
PIF4: 818903"
  },
  {
    "caption": "I RT-qPCR analysis showing that PIF4-induced expression of target genes is partially dependent the function of BIC1 and BIC2. The seedlings growth conditions were same as (G). The PP2A gene was analyzed as an internal control. Data are means ± SD (n=3). **p < 0.01, as determined by Student's t-test.",
    "ncbi_link": "BIC2: 823570
BIC1: 824440
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "J, K Phenotypic analyses showing that BIC1-induced hypocotyl elongation is largely dependent on the function of PIFs. The Col-0, pifQ, 35S:BIC1-Flag, 35S:BIC1-flag/pifQ #7 and BIC1-flag/pifQ #8 plants were grown for 5 days under long-day conditions. Images of the representative seedlings are shown in (J) and the hypocotyl lengths of indicated genotypes were measured and are shown in (K). Data are means ± SD (n>20). **p < 0.01, as determined by Student's t-test. Scale bar, 2 mm.",
    "ncbi_link": "Flag: 
flag: 
BIC1: 824440"
  },
  {
    "caption": "B ChIP-qPCR analysis showing the association of BIC1 with the promoter regions of BZR1/PIF4 target genes. The 6-d-old Col-0 and 35S:BIC1-Flag seedlings were used for ChIP assays.",
    "ncbi_link": "Flag: 
BIC1: 824440"
  },
  {
    "caption": "C ChIP-qPCR analysis showing that the association of BIC1 with the promoter regions of BZR1/PIF4 target genes is dependent on PIFs. The 6-d-old 35S:BIC1-Flag and 35S:BIC1-Flag/pifQ seedlings were used for ChIP assays.",
    "ncbi_link": "Flag: 
BIC1: 824440"
  },
  {
    "caption": "D ChIP-qPCR analysis showing that the enrichment of BZR1 in the promoter regions of its target genes is dependent on BICs. The 10-d-old 35S:BZR1-MYC and 35S:BZR1-MYC/bic1bic2 seedlings were treated with 1 μM epibrassinolide (eBL) for 3 h and then collected for ChIP assays.",
    "ncbi_link": "MYC: 
bic2: 823570
bic1: 824440
BZR1: 843845"
  },
  {
    "caption": "E ChIP-qPCR analysis showing that the enrichment of PIF4 in the promoter regions of its target genes is dependent on BICs. The 6-d-old 35S:PIF4-MYC and 35S:PIF4-MYC/bic1bic2 seedlings were used for ChIP assays.",
    "ncbi_link": "MYC: 
bic2: 823570
bic1: 824440
PIF4: 818903"
  },
  {
    "caption": "A RT-qPCR analysis showing that BIC1 upregulates the transcriptional expression of PIF4. The Col-0, 35S:BIC1-YFP, 35S:BIC1-Flag and bic1bic2 plants were grown for 5 days under long-day conditions. The PP2A gene served as internal control. Data are means ± SD (n=3). Different letters indicate significant differences (Fisher's LSD, P< 0.05).",
    "ncbi_link": "Flag: 
YFP: 
bic2: 823570
BIC1: 824440
bic1: 824440
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "B Transcript levels of BIC1 and PIF4 in transgenic plants containing a chemical-inducible construct pERGW-BIC1. 8-d-old pERGW-BIC1 seedlings were treated with 10 μM estradiol for indicated time points before harvest for RNA extraction and RT-qPCR analysis. The PP2A gene served as internal control. Data are means ± SD (n=3).",
    "ncbi_link": "BIC1: 824440
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "C ChIP-qPCR analysis showing the association of BIC1 with the promoter regions of PIF4. The top panel shows the diagram of the promoter structure of PIF4. Arrows indicate the primer positions for ChIP-qPCR. G-box, CACGTG. The 6-d-old Col-0 and 35S:BIC1-Flag seedlings were used for ChIP assays. The chromatin of each sample was immunoprecipitated (IP) using an anti-Flag or not (Mock). Precipitated DNA was quantified by qPCR, and DNA enrichment is displayed as the ratio between IP and Mock, normalized to that of PP2A as an internal control. Data are means ± SD (n=3). *p < 0.05, as determined by Student's t-test.",
    "ncbi_link": "Flag: 
BIC1: 824440
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "D RT-qPCR analysis showing the transcript levels of endogenous PIF4 in the 5-d-old Col-0, 35S-PIF4 and PIF4-HA seedlings. The PP2A gene served as internal control. Data are means ± SD (n=3).",
    "ncbi_link": "HA: 
PIF4: 818903
PP2A: 843333"
  },
  {
    "caption": "E Transient expression assays in Arabidopsis protoplasts showing that BIC1 and BZR1/PIF4 synergistically activate PIF4 promoter. The ProPIF4:LUC reporter was co-transformed with the indicated effector constructs. The LUC/REN ratios represent the ProPIF4:LUC activity relative to the internal control (REN driven by the 35S promoter). Error bars represent SD (n = 3). *p < 0.05, as determined by Student's t-test.",
    "ncbi_link": "LUC: 
REN: 
BIC1: 824440
BZR1: 843845
PIF4: 818903"
  },
  {
    "caption": "F LCI assays showing that TaBIC1 interacts with TaBZR1. Leaf epidermal cells of Nicotiana benthamiana were co-transformed with nLUC-TaBIC1 or nLUC and cLUC-TaBZR1 or cLUC as indicated.",
    "ncbi_link": "BIC1: 
BZR1: 
LUC: "
  },
  {
    "caption": "H BiFC assays showing the interaction of TaBIC1 and TaBZR1 in nucleus. Leaf epidermal cells of Nicotiana benthamiana were co-transformed with nYFP-TaBIC1 and cYFP-TaBZR1. The yellow dots represent interaction signals. BF, bright field. Scale bars, 20 μm.",
    "ncbi_link": "BIC1: 
BZR1: 
YFP: "
  },
  {
    "caption": "A-D. RNA blots were hybridized to AMV-specific probes to reveal accumulation of viral RNA in double (de) and triple (te) ect2/3/4 (A, B) or ect2/3/5 (C, D) mutants compared to WT plants. A and C show local infection at 3 days post-inoculation (dpi); B and D show systemic infection in aerial tissue at 7 dpi. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Dashed lines indicate non-contiguous samples analyzed on the same membrane. Ethidium bromide staining of ribosomal RNAs (EB) was used as RNA loading control. Error bars indicate standard deviations. Asterisks indicate significant differences from the WT (*: p < 0.05; **; p < 0.01) using the Student's t-test (n = 4). AU, arbitrary units.",
    "ncbi_link": "ect2: 820548"
  },
  {
    "caption": "A, RNA-blot analysis of AMV systemic infection in plants expressing ECT2WT-mCherry (WT) or ECT2W464A-mCherry (W464A) in the de23 background (A) at 7 days post-inoculation. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. In A, upper and lower panels show independent complementation transgenic lines, and different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "ncbi_link": "mCherry: 
ECT2: 820548"
  },
  {
    "caption": "B. RNA-blot analysis of AMV systemic infection in plants expressing in vir-1 plants (B) at 7 days post-inoculation. Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. In B, dashed line indicates non-contiguous samples that are analyzed on the same membrane. Error bars indicate standard deviations. Asterisks indicate significant differences from the WT (**: p < 0.01) applying Student's t-test (n = 4). AU, arbitrary units.",
    "ncbi_link": "vir-1: 819736"
  },
  {
    "caption": "A. ADAR expression (TPM - Transcripts Per Kilobase Million - mapping) in five samples of ECT2-FLAG-ADAR (S1-S5) and FLAG-ADAR (S6-S10) transgenic lines.",
    "ncbi_link": "FLAG: 
ADAR: 31130
ECT2: 820548"
  },
  {
    "caption": "A, Systemic infection of rosettes at 7 days post-inoculation (dpi) (A) Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. #1 and #2 correspond to the progeny of two different quadruple homozygous F2 siblings derived from the alkbh9b x te235 cross. Error bars show standard deviations. AU, arbitrary units. Different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "ncbi_link": "alkbh9b: 816307"
  },
  {
    "caption": "B. Systemic infection of rosettes and floral stems at 20 dpi (B). Each panel shows a representative RNA blot displaying AMV RNAs 1-4 (left) and its quantification histogram (right). Ethidium bromide staining of rRNAs (EB) was used as RNA loading control. Genotypes are indicated on the top of each northern blot. #1 and #2 correspond to the progeny of two different quadruple homozygous F2 siblings derived from the alkbh9b x te235 cross. Error bars show standard deviations. AU, arbitrary units. Different letters indicate statistical differences according to Fisher's Least Significant Difference (LSD) (p < 0.05).",
    "ncbi_link": "alkbh9b: 816307"
  },
  {
    "caption": "A. Schematic representations of the annotated ECT2 gene (AT3G13460.1, top) or protein (bottom) showing the deletion of the Tyr-rich region (ΔN5) in ECT2ΔN5-mCherry lines.",
    "ncbi_link": "mCherry: 
AT3G13460.1: 820548
ECT2: 820548"
  },
  {
    "caption": "C. Protein blot developed with mCherry antisera to show accumulation of ECT2WT-mCherry or ECT2ΔN5-mCherry fusion proteins in pools of the same samples used in panel B. Proteins on the membrane were stained with Coomassie-blue as loading control (lower panel).",
    "ncbi_link": "mCherry: 
ECT2: 820548"
  },
  {
    "caption": "(J) Citrate synthase activity ± 16-hour treatment with 20 μM BAM15 (N=10 per condition). (K) mtDNA (COX2:18S) ± 16-hour treatment with 20 μM BAM15 (N=6 per condition).",
    "ncbi_link": "18S: 
COX2: 17709"
  },
  {
    "caption": "I) Representative immunoblot and quantitative analysis (N=5 per condition; P<0.0001) of AMPK demonstrating loss of function following transfection with an shAMPK construct in C2C12 myotubes.",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "J) Representative respirometry plot of intact cells ± shAMPK and 16 hour BAM15 treatment in C2C12 myotubes cells sequentially injected with oligomycin, FCCP, and a cocktail of rotenone and antimycin a (N=5 per condition)",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "K) basal and ATP-linked respiration, proton leak, maximal uncoupling, and spare respiratory capacity (N=5 per condition). Basal: shEV vs. shEV + BAM15 (P=0.0317), shEV + BAM15 vs. shAMPK (P<0.0001), shEV + BAM15 vs. shAMPK + BAM15 (P<0.0001). ATP: shEV vs. shAMPK + BAM15 (P=0.0026), shEV + BAM15 vs. shAMPK + BAM15 (P=0.0003), shAMPK vs. shAMPK + BAM15 (P=0.040). Proton leak: shEV vs. shEV + BAM15 (P=0.0052), shAMPK vs. shAMPK + BAM15 (P=0.0394). Maximal: shEV vs. shAMPK + BAM15 (P<0.0001), shEV + BAM15 vs. shAMPK + BAM15 (P<0.0001), shAMPK vs. shAMPK + BAM15 (P<0.0001). Spare Capacity: shEV vs. shAMPK (P=0.0028), shEV vs. shAMPK + BAM15 (P<0.0001), shEV + BAM15 vs. shAMPK (P<0.0001), shEV + BAM15 vs. shAMPK + BAM15 (P<0.0001), shAMPK vs. shAMPK + BAM15 (P<0.0001).",
    "ncbi_link": "AMPK: 105787///108079
AMPK: 108079///105787"
  },
  {
    "caption": "L) [3-3H]glucose uptake ± shAMPK, 16 hour BAM15 treatment, and 30 minute insulin stimulation in C2C12 myotubes (N=3 per condition). No insulin: shEV vs. shEV + BAM15 (P=0.0001). Insulin: shEV vs. shEV + BAM15 (P=0.0142).",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "-O (M) Representative immunoblots and quantitative analysis of (N) AKT (shEV + insulin: P=0.0128, shAMPK - insulin: P=0.0018, shAMPK + insulin, P=0.0124), and (O) AS160 (shEV - insulin: P=0.0283, shEV + insulin: P=0.0137) phosphorylation ± shAMPK, 16 hour BAM15 treatment, and 15 minute insulin stimulation in C2C12 myotubes (N=3 per condition).",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "(L-N) mRNA expression of transcriptional regulators of lipogenesis and lipolysis in iWAT (N=7 per group). Srebf1 (P<0.0001), Mlxipl (P=0.0018), Scd1 (P<0.0001), FASN (P=0.0009), LIPE (P=0.0015), Pnpla2 (P<0.0001), PPARg (P<0.0001).",
    "ncbi_link": "FASN: 14104
LIPE: 16890
Mlxipl: 58805
Pnpla2: 66853
PPARg: 19016
Scd1: 20249
Srebf1: 20787"
  },
  {
    "caption": "B. The ER marker ER-tdTomato (magenta) is co-localized with ectopically expressed Wrb-EGFP (green) in inner saccular HCs of 5-dpf zebrafishlarvae ('control' refers to either wild-type or +/pwi fish that were picked in a phenotypic screen and did not exert any abnormal behavioral phenotype). While the left HC solely expressed ER-tdTomato, the neighboring HC expressed both, ER-tdTomato and Wrb-GFP. Colocalization between both proteins occurs in areas exhibiting white pixels. Scale bars: 5 µm",
    "ncbi_link": "pwi: 335756"
  },
  {
    "caption": "D. Projection of confocal sections of inner ear HCs of 5-dpf control (D) and Wrb-deficient pwi mutant fish (wrb pwi/pwi; D'), showing strongly reduced otoferlin immunofluorescence in the mutant HCs. The color look-up table used represents higher pixel intensities with warmer colors.",
    "ncbi_link": "pwi: 335756
Wrb: 335756
wrb: 335756"
  },
  {
    "caption": "E. A representative transgenically-rescued pwi-mutant HC (white arrow), expressing Wrb-GFP, exhibits a strongly increased otoferlin signal (magenta) in direct comparison to the neighboring non-rescued mutant HCs. (E') Same image as in E but intensity-coded for otoferlin fluorescence.",
    "ncbi_link": "pwi: 335756"
  },
  {
    "caption": "H. Quantification of otoferlin immunohistochemistry data shown in (D) from hair cells of control (n = 88 HCs from three 5-dpf larva), wrb pwi/pwi (n = 80 HCs from 3 sibling larva) normalized against the mean intensity value of the control group and Wrb-GFP transfected wrb pwi/pwi zebrafish inner ears. Mutant HCs showed ~82% reduction in otoferlin fluorescence intensity when compared with control HCs imaged under the same conditions. Otoferlin fluorescent intensity of Wrb-EGFP transfected mutant HCs (n = 24, from three, 5-dpf larva) showed significant increases compared to adjacent Wrb-EGFP negative mutant HCs (n = 24 from the same larva). Fluorescent intensity values were normalized with the average value of Wrb-EGFP negative HCs. ***p<0.001",
    "ncbi_link": "pwi: 335756
wrb: 335756"
  },
  {
    "caption": "I-I'. Acoustic startle reflex measurements of (I) live, intact, 5-dpf control (n = 20) and wrb pwi/pwi (n = 18) zebrafishlarva, where almost 100% of the larva responded to five successive acoustic stimuli at 3 seconds intervals. In wrb pwi/pwi animals, only 39% of larva responded to the first stimulus, thereafter, the number of responding larva decreased rapidly to less than 6%. (I') Acoustic startle reflexes of 5-dpf zebrafish larva after injection with either EGFP capped mRNA (control, n = 16, or wrb pwi/pwi n = 17), Wrb-EGFP capped mRNA (control, n = 20, or wrb pwi/pwi n = 20) or two different concentrations of otoferlin mRNA (1x: control, n = 13; wrb pwi/pwi n = 11; 2x: control, n = 16; wrb pwi/pwi n = 6). In contrast to EGFP mRNA injection, Wrb-EGFP as well as otoferlin mRNAs could partially rescue the acoustic startle reflex in the mutants, while not displaying detrimental effects on overall zebrafish morphology and development. Please note the dose-dependent effect of otoferlin mRNA injection. Similar results as in 1x EGFP mRNA were also obtained from injection of 2X EGFP mRNA as control (data not shown). Measurements from two (2x otoferlin) or three (all other) different experiments were compiled in the graph.",
    "ncbi_link": "otoferlin: 100331283///557476
pwi: 335756
Wrb: 335756
wrb: 335756"
  },
  {
    "caption": "A. HZZ-OTOFop, carrying a C-terminal glycosylation site (opsin tag) was purified alone or in complex with wild-type or an ATPase-deficient mutant version of TRC40 and incubated in the absence or presence of ER-derived rough microsomes (RM). Membrane integration (glycosylation) was monitored by SDS-PAGE and immunoblot using an anti-opsin antibody. Where indicated, EndoH was used to remove N-linked oligosaccharides.",
    "ncbi_link": "TRC40: 325704"
  },
  {
    "caption": "B. HZZ-OTOFop in complex with wild-type or mutant TRC40 was incubated with RM in the presence or absence of ATP and membrane insertion was monitored by opsin-specific immunoblot.",
    "ncbi_link": "TRC40: 325704"
  },
  {
    "caption": "C. HZZ-OTOFop in complex with wild-type TRC40 was incubated in the presence of RM, trypsin-treated rough microsomes (TRM) or in the presence of WRBcc or CAMLcyt. Membrane insertion was monitored by opsin-specific immunoblot.",
    "ncbi_link": "TRC40: 325704"
  },
  {
    "caption": "D. Quantification of relative protein glycosylation shown in B (n = 3). Data are represented as mean ± SEM. TRC40gr, mutated version of TRC40; **p<0.01; ***p<0.001 (Student's two-sample t-test).",
    "ncbi_link": "TRC40: 325704"
  },
  {
    "caption": "A. Grand averages of auditory brainstem responses (ABR) from Wrbfl/fl:CreA (red traces; SEM pink) and Wrb+/+:CreA (black traces; SEM grey) mice. ABRs were recorded for three separate age groups (A-A'', as indicated in the graph) using click stimulation at 80 dB (peak equivalent) and 20 Hz stimulation rate. There was an age- progressive reduction of ABR amplitude in Wrbfl/fl:CreA mice.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "B. ABRs from Wrbfl/fl:CreA mice showed a progressive threshold increase, Wrb+/+:CreA mice and Wrbfl/fl mice lacking Cre recombinase had normal thresholds. Statistical comparison of the threshold at 12 kHz was done by Kruskal-Wallis test, p values are from post-hoc Dunn's multiple comparison test. Measurements in which no ABR was observed at the maximal available tone burst level (90 dB) or click level (120 dB) scored as 100 dB threshold. Data are represented as mean ± SEM.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "A-D. Representative maximum projections of confocal sections of (A-B) P14 and (C-D) P20 Wrb+/+:CreA and Wrbfl/fl:CreA apical turn organs of Corti following immunolabeling against otoferlin (green) and Vglut3 (magenta) processed and imaged under identical conditions. A'-D' show individual otoferlin stainings with an intensity-coded lookup table. A''-D'' present single xz projections at a central point through a representative IHC to illustrate otoferlin subcellular distribution. Scale bars in A-D' represent 10 μm, in A''-D'' 2 µm. Note the dramatic reduction in otoferlin fluorescence and the alteration in its distribution as well as a change in cell shape and position of nuclei (for detailed analysis of cell shape and nuclei position, please refer to Figure EV5).",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "E-G. Semiquantitative analysis of otoferlin immunofluorescence in the apical parts of IHCs from Wrbfl/fl:CreA mice using averaged regions of interests in cell's maximal projections (outlined with a dotted line in G for a single representative IHC) normalized to the maximum values observed in the respective control IHCs. Averaged supra nuclear coronal line profiles as illustrated with a dashed line in G are shown for (F) P14-16 and (F') P18-21 IHCs. ***p<0.001 versus Wrb+/+:CreA",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "H-J. Semiquantitative analysis of otoferlin immunofluorescence in the basal parts of IHCs from Wrbfl/fl:CreA mice using averaged regions of interests in cell's maximal projections (outlined with a dotted line in J for a single representative IHC) normalized to the maximum values observed in the respective control IHCs. Averaged supranuclear coronal line profiles as illustrated with a dashed line in G are shown for (I) P14-16 and (I') P18-21 IHCs. ***p<0.001 versus Wrb+/+:CreA",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "A. Representative electron micrograph of a Wrb+/+:CreA IHC ribbon synapse. Scale bar: 120 nm.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "B-B'. In Wrbfl/fl:CreA (depicted are two consecutive ultrathin sections) IHCs, accumulations of large partially amorphous vesicles were observed close to ribbon synapses (red arrows), but also further away in the cytoplasm (cyan arrows). Moreover, cisternal structures resembling (r)ER are found unusually close to the ribbon (orange arrow in B'). Scale bar: 120 nm.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "E. Quantification in random ultrathin sections (Wrb+/+:CreA n = 28, from two animals; Wrbfl/fl:CreA n = 44, from three animals) of the numbers of membrane-proximal \"MP\" vesicles (in close proximity to membrane and ribbon); vesicles within a 100 nm range along the active zone membrane; vesicles at the lower \"proximal\" and the upper \"distal\" half of the ribbon as well as vesicle >70 nm (\"large vesicles\") in a radius of 800 nm around the ribbon. The vesicle number was significantly reduced in Wrbfl/fl:CreA IHCs at both ribbon parts but not at the presynaptic membrane.F. Average vesicle diameters of the membrane-proximal vesicles and the vesicles at both halves of the ribbon. The mean vesicle diameter increases significantly at both parts of the ribbon in Wrbfl/fl:CreA IHCs. Data are represented as mean ± SEM. Student's two-sample t-test ***p<0.001",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "A. Ca2+ current-voltage relationship of P14-P17 IHCs of Wrbfl/fl:CreA (n = 17 IHCs) and Wrb+/+:CreA (n = 15 IHCs) mice in 2 mM extracellular [Ca2+] showed no change in amplitude or voltage-dependence of the Ca2+ current. Data are represented as mean ± SEM.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "B. Representative Ca2+ current (top) and Cm changes (bottom) in Wrbfl/fl:CreA and Wrb+/+:CreA IHCs in response to a 20-ms step depolarizations to -14 mV (the potential eliciting the maximum Ca2+ current).",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "C. Representative Ca2+ current (top) and Cm changes (bottom; finite impulse response filtered) in Wrbfl/fl:CreA and Wrb+/+:CreA IHCs in response to a 100 ms step depolarizations to -14 mV.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "D. Exocytic ΔCm (top) and corresponding Ca2+ current integrals, QCa (bottom) for various depolarization durations. Data are grand averages of the cells' means. Exocytic ΔCm was reduced in the knockout from 20 ms onwards, indicating reduced sustained exocytosis. Data from OtofPga/Pga animals were replotted for direct comparison from (Pangrsic et al, 2010).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "E. ΔCm/QCa2+ ratio indicates a lower efficacy of Ca2+ influx in driving exocytosis in Wrbfl/fl:CreA IHCs, for stimuli of 20 ms or longer. Data represents means ± SEM; *p<0.05; **p<0.01; ***p<0.001",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "A. All SGNs of Wrbfl/fl:CreA mice had spontaneous firing rates (SR) below 20 Hz (p>0.05, Kolmogorow-Smirnov test).",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "B. Representative tuning curves from Wrbfl/fl:CreA and Wrb+/+:CreA SGNs indicating preserved active cochlear amplification despite disruption of Wrb in IHCs.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "C. Normal thresholds at the characteristic frequency (CF) in Wrbfl/fl:CreA SGNs.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "D-D''. Mean poststimulus time histograms (PSTH) ± SEM of Wrbfl/fl:CreA and Wrb+/+:CreA SGNs in response to 50 ms tone bursts presented at CF, 30 dB above threshold at stimulus rates of 2 Hz (D), 5 Hz (D'), or 10 Hz (D''). While the general response pattern was preserved, spike rates were drastically reduced in Wrbfl/fl:CreA SGNs, especially at higher stimulus rates. Data from auditory neurons (SGN and cochlear nucleus) of OtofPga/Pga animals were replotted for direct comparison from (Pangrsic et al, 2010).",
    "ncbi_link": "Cre: 
Otof: 83762
Wrb: 71446"
  },
  {
    "caption": "E. Spike rates in response to sound onset (maximum rate in PSTH with 0.5 ms binwidth) and adapted rates (averaged between 35-45 ms after stimulus onset) were significantly lower in Wrbfl/fl:CreA SGNs (stimulus rate 5 Hz; p<0.001).",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "F. In line with the reduction in spike rates, first spike latency (FSL) following stimulus onset was greatly increased in Wrbfl/fl:CreA SGNs compared to Wrb+/+:CreA (stimulus rate 5 Hz; p<0.001).",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "G. Illustration of the stimulus paradigm for forward masking experiments: a 100 ms masker tone presented at CF, 30 dB above threshold was followed by a silent interval of variable duration and a 15 ms probe tone (CF, 30 dB above threshold). Bottom: in Wrbfl/fl:CreA SGNs, the response to the first 5 ms of the masker probe tone tone (shown as a fraction of the response to the first 5ms of the masker) was strongly reduced, and the half time of recovery (from normalized curves) was increased from 39.2 ± 12.2 ms in Wrb+/+:CreA to 215.7 ± 51.2 ms in Wrbfl/fl:CreA SGNs (p<0.001, Mann-Whitney U test). Data represent means ± SEM.",
    "ncbi_link": "Cre: 
Wrb: 71446"
  },
  {
    "caption": "D-E. Cochlear microphonic potentials (CM), summating potential (SP) and compound action potential (CAP) recorded through transtympanic electrocochleography (ECochG) in response to clicks at decreasing stimulus intensities are superimposed on the corresponding potentials recorded from one normally-hearing control (range as measured at 120 dB 4.31-28.02 µV in 20 normally-hearing children). Means and standard errors of peak latency and amplitude are also reported for each potential category. The ECochG waveform resulting from CM cancellation in the control begins with an abrupt negative deflection, the SP, followed by a negative peak, the neural CAP. In the child with the OTOF TMD mutation, the ECochG responses begin with a rapid negative deflection that peaks at the same latency as the SP in the control and has comparable amplitude. This is followed by a low-amplitude negative potential that peaks at the same CAP in controls but shows a markedly prolonged duration. In all graphs time \"0\" refers to CM onset. R: right, L: left.F. Means and standard errors of peak latency and amplitude are reported for each potential category.",
    "ncbi_link": "OTOF: 9381"
  },
  {
    "caption": "A) Distribution curve of replication fork rates for Mybl2+/+ and Mybl2Δ/Δ ESCs. Statistical analysis was performed using the Mann Whitney U test. n=6 experimental replicates. A minimum of 490 replication forks were counted.( **** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "B) Left panel: representative elongating replication forks (stable and unstable). Quantification of the average IdU/CldU ratio in the Mybl2+/+ and Mybl2Δ/Δ ESCs. Percentage of highly unstable forks (ratio above 2) are indicated. Y-axis was cut to change scale and display large values. Statistical analysis was performed using the Mann Whitney U test. (**** p< 0.0001). At least 450 ratios were recorded from 6 experimental replicates.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C) The length of both CldU labels surrounding IdU tracks (newly fired origins) was measured before calculating a ratio representing symmetry around new origins. Quantification of the average positive ratio in the Mybl2+/+ and Mybl2Δ/Δ ESCs. Y-axis was cut to change scale and display large values. Statistical analysis was performed using the Mann Whitney U test. 55 and 75 ratios were recorded in the Mybl2+/+ and Mybl2Δ/Δ respectively from 3 replicates ( **** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "D) Representative image showing the presence of UFB by positive Immunostaining for PICH. (Scale bar 10μm). Frequency of anaphases positive for UFBs relative to all anaphases in the Mybl2+/+ and Mybl2Δ/Δ ESCs. At least 75 anaphases were counted per experimental group from 3 independent experiments. Statistical analysis was performed using an unpaired two-tailed t-test (**** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "E) Representative images for comets in Mybl2+/+ and Mybl2Δ/Δ untreated and Mybl2+/+ and Mybl2Δ/Δ plus CPT (20x magnification). (Scale bar 50μm).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "F) Quantification of the mean and distributions of olive tail moments in Mybl2+/+ and Mybl2Δ/Δ untreated and CPT-treated. Y-axis was cut to change scale and display large values. Statistical analysis using Mann Whitney U tests. At least 300 comets were measured for each group from 5 experimental replicates (**** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "G) Frequency of EdU positive cells with over 6 53BP1 foci in Mybl2+/+, Mybl2Δ/Δ untreated and Mybl2+/+ and Mybl2Δ/Δ plus CPT. Error bars represent SEM. Statistical analysis using unpaired two-tailed t-test. At least 200 EdU positive nuclei were analysed from 4 experimental repeats.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "A) Cells were treated for 1.5 hours with 5µM CPT, before sequential addition of IdU and CldU for 20 minutes each. Frequency of new firing origins (relative to total structures counted) from Mybl2+/+ and Mybl2Δ/Δ ESCs treated or not with CPT (n=3 independent experiments; Error bars indicate SEM). Statistical analysis using two- tailed unpaired t-test.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "(B) Distribution of replication rate in Mybl2+/+ and Mybl2Δ/Δ ESC treated or not with CPT as above. Statistical analysis was carried out using unpaired Mann Whitney U tests. A minimum of 200 forks were quantified for each of the genotypes and conditions shown from 3 independent repeats (*p < 0.05; **p< 0.01; ***p< 0.001; **** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C) ESCs were treated with or without CPT for 4 hours before 0.1ug/ml colcemid was added during the final 3.5 hours of treatment. Representative image of H3-pS10 positive cells (turquoise). (Scale bar 10μm). Frequency of H3-pS10 positive cells in Mybl2+/+ and Mybl2Δ/Δ ESCs. Data from three independent experiments. Error bars represent SEM. Statistical analysis was carried out using a two-tailed unpaired t-test (*p < 0.05; **p< 0.01; ns= no significant).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "D) P-CDK1 (Tyr15), CDK1 and Beta-actin expression levels of Mybl2+/+ and Mybl2Δ/Δ ESCs with or without CPT treatment analyzed by immunoblotting. Bar graph represents average band density of P-CDK1 in Mybl2Δ/Δ ESCs relative to loading control and relative to the MYBL2+/+ from 6 repeats. Error bars represent SEM. Statistical analysis was carried out using a two-tailed unpaired t-test (**p< 0.01).",
    "ncbi_link": "Mybl2: 17865
MYBL2: 17865"
  },
  {
    "caption": "A) Immunoblot showing the levels of phosphorylated CHK1 (Ser345) and GAPDH in the Mybl2+/+ and Mybl2Δ/Δ ESCs with or without CPT treatment (2.5µM CPT for 4 hours).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "B) Immunoblot showing the levels of P-CHK1 (Ser345) and CHK1 in irradiated Mybl2+/+, and Mybl2Δ/Δ ESCs with or without 3 hours inhibitor treatment: ATR (AZ20, 5µM) and ATM (Ku60019, 10µM). Cells were also exposed to 5Gy irradiation before the final hour of inhibitor treatment. Bar graph (lower panel) represents average band density of P-CHK1 in Mybl2Δ/Δ ESCs relative to CHK1 and relative to untreated cells. Mybl2+/+ from two independent repeats and Mybl2Δ/Δ ESCs from three independent repeats. Error bars represent SD. Statistical analysis was carried out using a two-tailed unpaired t-test (*p< 0.05).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C) Cells were treated for 1.5 hours with 5µM AZ20, before sequential addition of IdU and CldU for 20 minutes each. Dot plot representing the effect of ATR inhibition upon replication rate in Mybl2+/+ and Mybl2Δ/Δ ESC. Statistical analysis of distributions was carried out using unpaired Mann Whitney U tests. A minimum of 240 forks were quantified for each of the genotypes and conditions shown from 2 independent repeats (**** p< 0.0001)",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "D) Frequency of new firing origins (relative to total structures counted) from Mybl2+/+ and Mybl2Δ/Δ ESCs treated or not with ATR inhibitor AZ20. At least 500 replication structures were counted per treatment from two independent repeats. Statistical analysis using two- tailed unpaired t-test.(*p< 0.05; ns= no significant).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "E) Distribution and average of IdU/CldU fork ratio in Mybl2+/+ and Mybl2Δ/Δ ESCs with or without ATR inhibitor treatment. Percentage of highly unstable forks (ratio above 2) are indicated. Dotted line at 1 indicates positive ratio. Y-axis was cut to change scale and display large values. Statistical analysis was carried out using the Mann Whitney U test. At least 150 ratios were calculated per treatment group from two independent repeats (*p < 0.05; **p< 0.01; ***p< 0.001; **** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C) Distribution of the average IdU/CldU ratio in Mybl2+/+ and Mybl2Δ/Δ ESCs with or without ATM inhibitor treatment. Percentage of highly unstable forks (ratio above 2) are indicated. Dotted line at 1 indicates positive ratio. Y-axis was cut to change scale and display large values. Statistical analysis was carried out using the Mann Whitney U. At least 260 ratios were calculated per treatment group from 4 separate experiments ( **** p< 0.0001).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "D) Frequency of new fired origins for Mybl2+/+ and Mybl2Δ/Δ ESCs with or without ATM inhibitor treatment. Error bars represent SEM. Statistical analysis was carried out using unpaired t-test. At least 500 replication structures were counted per treatment group from 4 separate repeats.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "E) Frequency of anaphases positive for UFB positive cells (based on ERCC/PICH positive immunostaining) for Mybl2+/+, the Mybl2Δ/Δ and the Mybl2+/+ treated for 2 hours with ATM inhibitor (KU60019). Data represents at least 100 anaphases from each group from 2 experimental repeats. Statistical analysis was performed using an unpaired two-tailed t-test.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "F) Immunoblot showing the levels of phosphorylated ATM (Ser1987) and ATM in the Mybl2+/+ and Mybl2Δ/Δ ESCs with or without CPT treatment (10µM CPT for 2 hours). Bar graph (lower panel) represents average band density of P-ATM in Mybl2Δ/Δ ESCs treated with CPT relative to ATM and relative to wild type CPT treated cells from three independent repeats. Error bars represent SD. Statistical analysis was carried out using a two-tailed unpaired t-test.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "G) Distribution plot of replication speed in Mybl2+/+and ATM-/- ESC treated or not for 90 minutes with 10µM KU60019 (ATMi), before sequential addition of IdU and CldU for 20 minutes each. Statistical analysis was carried out using the Mann Whitney U test. At least 200 replication forks were counted from 3 separate experiments for wild type and ATM-/- and two separate experiments for ATM-/- treated with ATM inhibitor . ( **** p< 0.0001)",
    "ncbi_link": "ATM: 11920
Mybl2: 17865"
  },
  {
    "caption": "B and C) Distribution curve of replication fork rates for Mybl2+/+ and Mybl2Δ/Δ ESCs treated with mirin. Statistical analysis was performed using the Mann Whitney U test. n=3 experimental replicates. The value of the mean fork length is indicated above arrow ( **** p< 0.0001)",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "E) Frequency of new firing origins (relative to total structures counted) from Mybl2+/+ and Mybl2Δ/Δ ESCs treated or not with Mirin. At least 450 replication structures were counted per treatment from 3 independent repeats. Error bars represent SEM. Statistical analysis using two- tailed unpaired t-test.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "F) Distribution and the average IdU/CldU ratio in Mybl2+/+ and Mybl2Δ/Δ ESCs with or without MRE11 inhibitor treatment. The length of both incorporated labels for each elongating fork was measured in µm and the positive ratio was calculated. Percentage of highly unstable forks (ratio above 2) are indicated. Dotted line at 1 indicates positive ratio. Y-axis was cut to change scale and display large values. Statistical analysis was carried out using the Mann Whitney U test. At least 260 ratios were calculated per treatment group from 3 separate experiments.( **** p< 0.0001)",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C ) Frequency of new firing origins (relative to total structures counted) from Mybl2+/+ and Mybl2Δ/Δ ESCs treated or not with the indicated inhibitors: CDC7 inhibitor (PHA-767491) and/or ATM inhibitor (Ku60019). At least 300 replication structures were counted per treatment. Error bars represent SEM. Statistical analysis using two- tailed unpaired t-test (*p < 0.05).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "D ) Replication rate (kb/min) of Mybl2+/+ and Mybl2Δ/Δ ESCs treated with the indicated inhibitors. Statistical analysis was carried out using an unpaired Mann Whitney U test (**** p< 0.0001). Minimum three independent experiments. At least 270 forks were scored for non-ATM inhibitor treated groups, and a minimum of 130 for ATM inhibitor treated groups.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "E ) Fork stability (average IdU/CldU ratio) of Mybl2+/+ ESC and Mybl2Δ/Δ ESCs treated with the indicated inhibitors alone or in combination. At least 240 ratios were calculated for non-ATM inhibitor treated groups, and a minimm of 130 for ATM inhibitor treated groups. Y-axis was cut to change scale and display large values. Statistical analysis was carried out using Mann Whitney U test (**** p< 0.0001). Data for Mybl2+/+ ESCs treated with ATM inhibitor alone or in combination with CDC7 inhibitor, was collected from two independent experiments. For the rest of the conditions, a minimum of three independent repeats was performed.",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "F) Immunoblot showing the levels of CDC7 and actin in the Mybl2+/+ and Mybl2Δ/Δ ESCs. Bar graph (lower panel) represents average band density of CDC7 in Mybl2Δ/Δ ESCs relative to actin and relative to Mybl2+/+ ESCs from three independent repeats. Error bars represent SD. Statistical analysis was carried out using a two-tailed unpaired t-test (ns=no significant).",
    "ncbi_link": "Mybl2: 17865"
  },
  {
    "caption": "C, Survival assays against substrates of QacA showed loss of activity against monovalent cationic antibacterials (TPP: Tetraphenylphosphonium, Et: Ethidium), while still retaining partial activity against divalent cations (Dq: Dequalinium, Ch:Chlorhexidine). EV: pBAD empty vector. n = 3 for biological replicates. CFU indicates colony forming units. Image color was inverted from black to white background to enhance clarity.",
    "ncbi_link": "QacA: 3921406"
  },
  {
    "caption": "G, Colocalization of QacAWT or QacAD411N (tagged with GFP) on E. coli spheroplasts (stained with DAPI for viability) with ICabs (labelled with NHS-Rhodamine) was screened against ICab A4 (left) and ICab B7 (right). n = 10-30 spheroplasts were imaged for each sample.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D, Survival assays of QacAΔEL7 and QacAD411N/ΔEL7 mutants in the presence of 10 μM Tetraphenylphosphonium (TPP) and 16 μM Chlorhexidine (Ch). Data from one representative biological replicate is shown here. Image colors were inverted for improved clarity.",
    "ncbi_link": "QacA: 3921406"
  },
  {
    "caption": "C Whole cell ethidium efflux assay done with E.coli JD838 cells expressing QacAWT or QacA5A. Empty vector (EV) was used as a control for the experiment. A graph of one independent replicate is shown with error bars representing S.E.M. of 6 technical replicates.",
    "ncbi_link": "QacA: 3921406"
  },
  {
    "caption": "G Survival assays of solely EL7 chimeric constructs compared against empty vector (EV) and QacAWT. One representative biological replicate is shown. Image color inverted for clarity.",
    "ncbi_link": "QacA: 3921406"
  },
  {
    "caption": "Whole cell-based ethidium efflux assay done with E.coli JD838 cells expressing QacAWT, its EL7 deletion construct (QacAΔEL7), and the chimeric mutants of LfrA and SmvA. All assays were done in at least 2 independent replicates. One representative replicate shown with data normalized to highest value in each trace. Error bars depict S.E.M. for six technical replicates.",
    "ncbi_link": "LfrA: 66737507
QacA: 3921406
SmvA: 1253092"
  },
  {
    "caption": "I Whole cell-based ethidium efflux assay done with E.coli JD838 cells expressing QacAWT, its EL7 deletion construct (QacAΔEL7), and the chimeric mutants of LfrA and SmvA. All assays were done in at least 2 independent replicates. One representative replicate shown with data normalized to highest value in each trace. Error bars depict S.E.M. for six technical replicates.",
    "ncbi_link": "LfrA: 66737507
QacA: 3921406
SmvA: 1253092"
  },
  {
    "caption": "(C) Quantitative real time PCR analysis showing head enrichment of dEsyt; the X-axis indicates the wild type tissues from which RNA was isolated and Y-axis indicates the dEsyt transcript level expression normalized to the loading control (RP49- Ribosomal protein 49), n=3 replicates (biological).",
    "ncbi_link": "Ribosomal protein 49: 
RP49: 
Esyt: 42929"
  },
  {
    "caption": "(D) Quantitative real time PCR analysis showing dEsyt transcript level expression in head RNA samples from wild type and sOD. Y-axis indicates the dEsyt transcript level expression normalized to the loading control (RP49- Ribosomal protein 49), n=3 replicates (biological).",
    "ncbi_link": "Ribosomal protein 49: 
RP49: 
Esyt: 42929
sO: 35662"
  },
  {
    "caption": "(H) Representative ON images showing the rescue of rhabdomere structural integrity in dEsytKO mutants on expressing the dEsyt::mCherry transgene. Genotypes of the flies are indicated on the left. Rearing conditions and the age of the flies are indicated on top.",
    "ncbi_link": "mCherry: 
Esyt: 42929"
  },
  {
    "caption": "(A) (i) Representative optical neutralization (ON) images showing rhabdomere structure of the indicated genotypes. Rearing conditions and the age of the flies are indicated on top. (*CD- Constant Dark). (ii) TEM images showing a single ommatidium from the photoreceptors of rdgB9 and rdgB9;dEsytKO mutants reared in 12 hr L/D cycle ( / ) for 2 days. Scale bar: 1µm (asterisk indicates degenerated rhabdomere).",
    "ncbi_link": "Esyt: 42929
rdgB: 32340"
  },
  {
    "caption": "(D) Graph showing ERG amplitude of rdgB9 and rdgB9;dEsytKO normalized to body weight. Y-axis shows the ratio of ERG amplitude of individual flies to their body weight. X-axis indicates genotypes. Each data point represents an individual fly tested. Error bar represents s.e.m.",
    "ncbi_link": "Esyt: 42929
rdgB: 32340"
  },
  {
    "caption": "(A) Confocal images showing the localization of endogenous dEsyt protein in photoreceptors of one day old dark reared flies probed with antibody against dEsyt. Scale bar: 5µm. dEsytKO shows no staining when probed with dEsyt antibody.",
    "ncbi_link": "Esyt: 42929"
  },
  {
    "caption": "(B) Confocal images showing the localization of exogenously expressed dEsyt::mCherry protein expressed using the eye specific Rh1-Gal4 in one day old dark reared flies. Rh1-Gal4 is shown as a control. A single ommatidium is shown. Scale bar: 5 µm. Phalloidin marks F-actin staining and highlights rhabdomeres R1-R7.",
    "ncbi_link": "Gal4: 855828
Rh1: 42367"
  },
  {
    "caption": "(C) Western blot from the head extracts of wild type and dEsytKO probed with the antibody against RDGB. Rearing conditions, age of the flies and genotype is indicated on top of the blot. Tubulin was used as the loading control.",
    "ncbi_link": "Esyt: 42929"
  },
  {
    "caption": "(D, E) Confocal images showing the localization of RDGB in wild type and dEsytKO photoreceptors of flies which are (D) 1 day old-dark reared and (E) 6 days old- exposed to constant illumination. For (D) and (E) RDGB visualized using an antibody against the endogenous protein. Rhabdomeres are outlined using phalloidin which marks F-actin. Scale bar: 5 µm.",
    "ncbi_link": "Esyt: 42929"
  },
  {
    "caption": "(C) TEM images of a single ommatidium from norpAP24 photoreceptors of flies reared in dark (i) day 1 and (iii) day 14, scale bar: 1µm (red asterisk indicates R7 photoreceptor). Magnified image showing a single photoreceptor from the same ommatidium (ii) day1 (iv) day 14. Scale bar: 200 nm. Arrows indicate the SMC forming an MCS with the microvillar PM. (D) Quantification of the number of MCSs per photoreceptor (from figure 6C), X-axis indicates the genotype and age of the flies and Y-axis indicates the number of MCS/photoreceptor (i) n=30 photoreceptors from 3 separate flies (R1-R6) (ii) n=9 photoreceptors from 3 separate flies (R7) ",
    "ncbi_link": "norpA: 31376"
  },
  {
    "caption": "(E) TEM images of a single ommatidium from (i) wild type and (iii) dEsytKO photoreceptors of 0-1 day old flies reared in dark, scale bar: 1µm (red asterisk indicates R7 photoreceptor) (ii, iv) Magnified image showing a single photoreceptor from the ommatidium image shown on the left. Scale bar: 200 nm. Arrows indicate the SMC forming an MCS with the microvillar PM. (F) Quantification of the number of MCS per photoreceptor of wild type day 1 v/s dEsytKO day 1 old flies reared in dark, X-axis indicates the genotype and age of the flies and Y-axis indicates the number of MCS/photoreceptor (i) n=30 photoreceptors from 3 separate flies (R1-R6) (ii) n=9 photoreceptors from 3 separate flies (R7).",
    "ncbi_link": "Esyt: 42929"
  },
  {
    "caption": "(A) TEM images of a single ommatidium from photoreceptors of (i) dEsytKO- day 1 (iii) dEsytKO- day 14 flies reared in dark, scale bar: 1 µm except for (Ai): 2 µm (red asterisk indicates R7 photoreceptor). (A-ii, iv) Magnified image showing a single photoreceptor from the ommatidium image shown on the left. Scale bar: 200 nm. Boxes represent the origin boxes for magnification. M- Microvillar plasma membrane, S- Sub microvillar cisternae, MCS- Membrane Contact Site, P- Pigment granules. (B) Quantification of the number of MCS per photoreceptor, X-axis indicates the genotype and age of the flies and Y-axis indicates the number of MCS/photoreceptor. n=9 photoreceptors from 3 separate flies for R7. ",
    "ncbi_link": "Esyt: 42929"
  },
  {
    "caption": "(C) TEM images of a single ommatidium from photoreceptors of (i) norpAP24;dEsytKO- day 1 (iii) norpAP24;dEsytKO- day 14 flies reared in dark, scale bar: 1 µm (red asterisk indicates R7 photoreceptor). (C-ii, iv) Magnified image showing a single photoreceptor from the ommatidium image shown on the left. Scale bar: 200 nm. Arrows indicate the SMC forming an MCS with the microvillar PM. (D) Quantification of the number of MCS per photoreceptor, X-axis indicates the genotype and age of the flies and Y-axis indicates the number of MCS/photoreceptor. (i) n=30 photoreceptors from 3 separate flies for R1-R6. (ii) n=9 photoreceptors from 3 separate flies for R7. ",
    "ncbi_link": "Esyt: 42929
norpA: 31376"
  },
  {
    "caption": "(E) TEM images of a single ommatidium from photoreceptors of (i) rdgB9-day1 and (iii) rdgB9;dEsytKO - day 1 flies reared in dark, scale bar: 1 µm (red asterisk indicates R7 photoreceptor). (E-ii, iv) Magnified image showing a single photoreceptor from the ommatidium image shown on the left. Scale bar: 200 nm. (F) Quantification of the number of MCS per photoreceptor for R1-R6 in 1 day old dark reared wild type (from Figure 5B i), rdgB9 and rdgB9;dEsytKO flies. n=30 photoreceptors from 3 separate flies. ",
    "ncbi_link": "Esyt: 42929
rdgB: 32340"
  },
  {
    "caption": "B. Survival curves of Bcs1l homozygotes without (GRAC) and with (GROX) alternative oxidase (AOX) expression (n=18-21/group). The median survival of GRAC mice was 210 days and of GROX mice 589 days with no gender difference Statistics: The survival data was analyzed using Log-rank (Mantel-Cox) test (p<0.0001)",
    "ncbi_link": "Bcs1l: 66821
alternative oxidase: 108950628
AOX: 108950628"
  },
  {
    "caption": "Gene expression of major transcriptional regulators of energy metabolism (PPAR-α, mitochondrial biogenesis (PGC-1α, TFAM) in heart at P150. (n=6/group) Box plot whiskers represent quartiles, maximum and minimum value (relative fold change 'FC' to WT). Statistics: one-way ANOVA followed by Tukey's test.",
    "ncbi_link": "PPAR-α: 19013
PGC-1α: 19017
TFAM: 21780"
  },
  {
    "caption": "Gene expression of major transcriptional regulators of energy metabolism HIF-1α) and stress responses (ATF4) in heart at P150. (n=6/group) Box plot whiskers represent quartiles, maximum and minimum value (relative fold change 'FC' to WT). Statistics: one-way ANOVA followed by Tukey's test.",
    "ncbi_link": "ATF4: 11911
HIF-1α: 15251"
  },
  {
    "caption": "mRNA expression of proline synthesis-related genes (n=6/group)) (H) Aldh18a1 and (I) Pycr1 at P150 box plots of mRNA expressions represent quartiles, minimum, and maximum value (relative fold change "FC&qu Statistics for graph one-way ANOVA followed by Tukey"s",
    "ncbi_link": "Aldh18a1: 56454
Pycr1: 209027"
  },
  {
    "caption": "B-E. Gene expression of Ca2+ channel gene (B) ryanodin receptor, RYR2, (C) sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2 or ATP2A2), (D) phospholamban (PLN), and (E) endothelial nitric oxide synthase NOS3 (n=6/group) Box plots for mRNA expressio represent quartiles, minimum and maximum value (relative fold change "FC&qu Statistics: one-way ANOVA followed by Tukey"s test for Significant differences between groups (p value) are indicated on graphs",
    "ncbi_link": "ATP2A2: 11938
Ca2+-ATPase: 11938
SERCA2: 11938
endothelial nitric oxide synthase: 18127
NOS3: 18127
phospholamban: 18821
PLN: 18821
RYR2: 20191"
  },
  {
    "caption": "Expression of neuronal nitric oxide synthase (NOS1) mRNA (F Bar graph represent mean±SD Statistics: one-way ANOVA followed by Tukey"s test for Significant differences between groups (p value) are indicated on graphs",
    "ncbi_link": "NOS1: 18125"
  },
  {
    "caption": "H. Cardiac gene expression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) (n=6/group) Box plots for mRNA expressio represent quartiles, minimum and maximum value (relative fold change "FC&qu Statistics: one-way ANOVA followed by Tukey"s test for Significant differences between groups (p value) are indicated on graphs",
    "ncbi_link": "DDAH1: 69219
dimethylarginine dimethylaminohydrolase 1: 69219"
  },
  {
    "caption": "(C) Decreased levels of free carnitine and modified  carnitine species in PKM2  KO cell lines as compared with their parental counterparts (n=4). Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001. n.s means no significance.",
    "ncbi_link": "PKM2: 5315"
  },
  {
    "caption": "(E) Increased acetyl-CoA  in PKM2 KO  MCF7 and MDA-MB 231cells as compared with their parental counterparts (n=4). (F) Decreased total  cholesterol in PKM2  KO MCF7  and  MDA-MB 231cells as compared with their parental counterparts (n=3). ( Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001. n.s means no significance.",
    "ncbi_link": "PKM2: 5315"
  },
  {
    "caption": "(G)  Western blot  analysis of TMEM33, ABCA1, SREBP1, HMGCR, SCAP, FASN, LDLR, FDFT1, I DI1, RNF5, INSIG 1 and 2, and Calnexin in  PKM2 KO MCF7 and MDA-MB-231 cells, and their respective parental cells. Arrow indicates nuclear SREBP1. P: precursor, N: nuclear.",
    "ncbi_link": "PKM2: 5315"
  },
  {
    "caption": "(A) Immunofluorescence of SREBP1 in  MCF7 parental and PKM2 KO cells by confocal imaging. Scale bar, 5μm. (B) Quantitation of nuclear SREBP1 intensity in A. n>=25 cells as in (A) from three different fields. ( Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05 and ∗∗∗p < 0.001.",
    "ncbi_link": "PKM2: 5315"
  },
  {
    "caption": "(G)  Western blot analysis of  TMEM33, RNF5,  SCAP, SREBP1, HMGCR,  LDLR, FDFT1,  IDI1, and PKM2 in wild type,  PKM2 KO, TMEM33 OE (pool), and two TMEM33OE clones (clones #1 and #8) MDA-MB-231 cells. Arrow indicates  nuclear SREBP1. N: nucleus  and P: precursor.",
    "ncbi_link": "PKM2: 5315
TMEM33: 55161"
  },
  {
    "caption": "(B) Western blot  analysis of PKM2, PKM1, NRF1,  TMEM33, RNF5 and SCAP levels in MEF  (PKM2fl/fl, Cre-ERT2) cells treated with 4-OHT in a time course  experiment.",
    "ncbi_link": "Cre: 2777477
PKM2: 18746"
  },
  {
    "caption": "(H)  RNF5 is involved in TMEM33 mediated SCAP polyubiquitination in  293T cells. 293T cells were stably transfected with shCtrl or shRNF5 constructs, then the indicated plasmids were co-transfected into shCtrl or shRNF5  expressing  293T cells for 18 hours followed by MG-132 treatment for 8 hours. FLAG  M2  beads were used for pull-down.",
    "ncbi_link": "RNF5: 6048
TMEM33: 55161"
  },
  {
    "caption": "(D)  qRT-PCR analyses of selected SREBPs downstream genes in shCtrl and shRNF5 PKM2  KO  MDA-MB-231  cells (n=3). Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001.",
    "ncbi_link": "PKM2: 5315
RNF5: 6048"
  },
  {
    "caption": "(G)  Cell proliferation of Ctrl and HA-RNF5 OE MCF7  cells measured by MTT assays (n=8). Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001.",
    "ncbi_link": "HA: 
RNF5: 6048"
  },
  {
    "caption": "(E)  Western blot  analyses of TMEM33  and RNF5 in  NRF1  overexpressed MCF7  clones. (F)  Western blot analyses of TMEM33 and RNF5 in shCtrl and shNRF1 PKM2 KO MCF7  cells. ( ",
    "ncbi_link": "NRF1: 4899
PKM2: 5315"
  },
  {
    "caption": "(G) Co-immunoprecipitation of  VCP with FLAG-tagged PKM1/2 in  PKM2 KO  293T  cells. FLAG-tagged  PKM1  or PKM2 construct was transiently transfected into PKM2  KO or parental  293T cells for 24 hours, followed by  pull-down using  FLAG-M2 beads. PKM1, PKM2  and  VCP  antibodies were used for  immunoblotting.",
    "ncbi_link": "FLAG: 
PKM1: 5315
PKM2: 5315"
  },
  {
    "caption": "(E) Representative H&E and IHC staining images of  TMEM33 and SCAP in WT and TMEM33  KO mouse livers. Scale bars, 100µm.",
    "ncbi_link": "TMEM33: 67878"
  },
  {
    "caption": "(F, G) Significant decrease of total plasma cholesterol  (F) and  LDL-C  (G) levels in  TMEM33-/- and +/-  mice relative to WT counterparts (n>=5). Data information: Data are displayed as means ± SD. Statistical significance was assessed using two-tailed Student's t-test, ∗p < 0.05 and ∗∗∗p < 0.001. n.s denotes no significance.",
    "ncbi_link": "TMEM33: 67878"
  },
  {
    "caption": "(B)  Tumor growth  curves of  PKM2  WT or KO  py8119  cell line  allografts in systemic PKM2  KO or WT  mice  (n=5). Data information: Data are displayed as means ± SD. Statistical significance was assessed using a two-tailed Student's t-test, ∗p < 0.05, ∗∗p < 0.01 and ∗∗∗p < 0.001.",
    "ncbi_link": "PKM2: 18746"
  },
  {
    "caption": "(B) RAW 264.7 cells transfected for 48 h with control (sc), MTMR6 or Jumpy siRNA, were pretreated for 30 min with 100 nM Bafilomycin A1 (BafA1), 10 μg/ml E64d and 10 μg/ml pepstatin, then incubated for 30 min in full or starvation media in the presence of BafA1, E64d and pepstatin. Cells were lysed and analysed by immunoblotting with anti-LC3 or anti‐actin. Densitometric LC3‐II/actin ratios are shown underneath the blot. Graph: LC3‐II/actin ratio for Jumpy siRNA in full medium is equal to or exceeds LC3‐II/actin ratio for control siRNA (sc) in starvation medium.",
    "ncbi_link": "Jumpy: 97287
MTMR6: 219135"
  },
  {
    "caption": "(C, D) RAW 264.7 cells were transfected for 36 h with control (scramble) or Jumpy siRNA, transfected once more with corresponding siRNA and mRFP‐GFP‐LC3 DNA construct overnight and incubated for 2 h in full or starvation media. Cells were fixed and LC3 puncta analysed by confocal fluorescence microscopy. (C) Representative confocal images of RAW 264.7 cells in full or starvation media after transfection with control (scramble) or Jumpy siRNA (siJumpy). Red and yellow arrows indicate GFP−RFP+ and GFP+RFP+ puncta, respectively. (D) Quantitation of number of LC3 puncta per cell, total puncta per cell (GFP+RFP+ and GFP−RFP+ puncta) GFP+RFP+ puncta per cell and GFP−RFP+ puncta per cell. Data, mean±s.e.m. n=5 independent experiments, 30 cells per experiments. *P0.05, **P0.01, ***P0.001 (t‐test). Scale bars, 5 μm.",
    "ncbi_link": "LC3: 66734///67443
Jumpy: 97287"
  },
  {
    "caption": "(E, F) C2C12 myoblasts were transfected for 48 h with control (scramble) or Jumpy siRNA, followed by a second transfection overnight with corresponding siRNA and mRFP‐GFP‐LC3 DNA construct. Cells were fixed and LC3 puncta were counted by confocal fluorescence microscopy. (E) Representative confocal images of C2C12 cells in full media after transfection with control (scramble) or Jumpy siRNA (siJumpy). (F) Quantification of the number of LC3 puncta per cell. Data, mean±SEM for n=3 (independent experiments), 30 cells per experiments. *P 0.05 (t-test). Scale bars, 10 μm.",
    "ncbi_link": "LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(G, H) C2C12 cells were transfected for 48 h with control (sc) (lanes 1, 2, 5, 6) or Atg5 siRNA (lanes 3, 4, 6, 7) followed by a second transfection for 48 h with same siRNA and control (lanes 1, 3, 5, 7) or Jumpy siRNA (lanes 2, 4, 6, 8). Cells were incubated for 1 h with or without 100 nM Baf A1, 10 μg/ml E64d and 10 μg/ml pepstatin in full media, lysed and analysed by immunoblotting with anti‐LC3 or anti‐actin (G). (H) Densitometric LC3‐II/actin ratios for samples treated with BafA1 and protease inhibitors from G (lanes 5-8). Inset shows Atg5 knock‐down by immunoblotting.",
    "ncbi_link": "Atg5: 11793
Jumpy: 97287"
  },
  {
    "caption": "(A) Proteolysis of long‐lived proteins in C2C12 myoblasts. C2C12 cells were transfected with control (scramble) or Jumpy siRNA (siJumpy), labelled overnight in media containing [3H] leucine, washed, incubated for 2 h in complete media (containing cold leucine) and incubated for 4 h in full or starvation media. Leucine release was calculated from radioactivity in the tricarboxylic acid‐soluble form relative to total cell radioactivity. Results shown represent mean±s.e.m. for combined data from three independent experiments.",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(B) Quantitation of p62 protein levels. C2C12 cells were transfected for 48 h with control (sc) or Jumpy siRNA and p62 levels analysed by immunoblotting, quantitated by densitometry and represented as a percentage of control. Data are mean±s.e.m. (n=4 independent experiments).",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(C) C2C12 cells were transfected for 48 h with control (sc) or Jumpy siRNA, incubated for 4 h with or without 100 nM Bafilomycin A1 in full media, lysed, probed for endogenous p62 and actin by immunoblotting and percentage of p62 were quantitated (mean±s.e.m., n=3).",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(D) C2C12 cells were transfected for 48 h with control (sc) (lanes 1, 2) or Beclin siRNA (lanes 3, 4) followed by a second transfection for 48 h with same siRNA and control (lanes 1, 3) or Jumpy siRNA (lanes 2, 4). Cells were lysed, probed for p62, Beclin and actin by immunoblotting and percentage of p62 were quantitated (mean±s.e.m., n=5).",
    "ncbi_link": "Beclin: 56208
Jumpy: 97287"
  },
  {
    "caption": "(E-M) C2C12 cells were transfected for 48 h with GFP, GFP‐Jumpy (Jumpy), GFP‐MTM1 (MTM1) or GFP‐MTMR2 (MTMR2), fixed and immunostained with anti‐p62 antibody (red). p62 puncta were quantitated by confocal fluorescence microscopy. Representative confocal images of GFP (E), GFP‐Jumpy (F), GFP‐MTM1 (G), GFP‐MTMR2 (H) transfected cells, immunostained for p62 (I), (J), (K) and (L), respectively. Scale bars, 5 μm. White lines represent outline of the cells. Quantitation of p62 puncta per cell (M). Bars, SEM (n=3 independent experiments, with an average of 30 cells per experiments).",
    "ncbi_link": "MTM1: 17772
Jumpy: 97287
MTMR2: 77116"
  },
  {
    "caption": "(N, O) C2C12 cells were transfected for 48 h with GFP, GFP‐Jumpy (Jumpy), GFP‐MTM1 (MTM1) or GFP‐MTMR2 (MTMR2), lysed, analysed for p62, GFP and actin by immunoblotting (N) and percentage of p62 were quantitated (mean±s.e.m., n=3) (O).",
    "ncbi_link": "MTM1: 17772
Jumpy: 97287
MTMR2: 77116"
  },
  {
    "caption": "(P, Q) C2C12 cells were transfected for 48 h with GFP or GFP‐Jumpy (Jumpy), incubated with or without 100 nM Bafilomycin A1 (BafA1) for 4 h, lysed, analysed for p62, GFP and actin by immunoblotting (P) and percentage of p62 were quantitated (mean±s.e.m., n=4) (Q). *P0.05, ***P0.001, †ns (t‐test).",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(A) Transient association of Jumpy WT with LC3+ organelles. Time lapse sequence of C2C12 myoblasts transfected for 24 h with GFP‐Jumpy WT and Cherry‐LC3 and analysed by live confocal microscopy in a 5LIVE Zeiss microscope. EBSS was added to the cells and z‐stacks collected at 3‐min intervals for a total of 45 min. The collected images were processed to generate a maximum projection (collapsing a 3D image into an x-y projection) for each time point. Arrows indicate colocalization of GFP‐Jumpy WT with LC3. Graph: Plots of relative fluorescence intensity (GFP fluorescence pixel intensity) over time of GFP‐Jumpy WT colocalizing with Cherry‐LC3+‐positive puncta indicated by arrows.",
    "ncbi_link": "LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(B-I) Association of Jumpy CS mutant with autophagic organelles. C2C12 cells were transfected for 24 h with GFP‐Jumpy C330S (Jumpy CS) and tdTomato‐LC3 (LC3), fixed and immunostained with anti‐G58K (Alexa 648‐labelled secondary antibody). Jumpy CS (green), LC3 (red) and G58K (white in D, H or blue in E, I). Boxed areas (B-E) are shown at higher magnification in the corresponding panel below (F-I). Scale bars, 2 μm. White arrows indicate colocalization between Jumpy CS, LC3 but not G58K, blue arrow indicates colocalization between Jumpy CS and G58K but not LC3.",
    "ncbi_link": "LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(A-H) C2C12 cells were transfected for 24 h with GFP‐Jumpy C330S (Jumpy CS) and tdTomato‐LC3 (LC3), fixed and immunostained with anti‐Atg16 (Alexa 648‐labelled secondary antibody). Jumpy CS (green), LC3 (red) and Atg16 (white in B and F or blue in D and H). Boxed areas (A-D) are shown at higher magnification in the corresponding panel below (E-H). White arrows indicate colocalization among Jumpy CS, LC3 and Atg16, yellow arrow indicates colocalization between Jumpy CS and LC3 but not Atg16, blue arrow indicates colocalization between Jumpy CS and Atg16 but not LC3.",
    "ncbi_link": "LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(K-R) C2C12 cells were transfected for 24 h with GFP‐Jumpy C330S (Jumpy CS) and tdTomato‐LC3 (LC3), fixed and immunostained with anti‐Atg12(M) antibody. Jumpy CS (green), LC3 (red) and Atg12 (white in L, P or blue in N, R). Boxed areas (K-N) are shown at higher magnification in the corresponding panel below (O-R). White arrows indicate colocalization among Jumpy CS, LC3 and Atg12, yellow arrow indicates colocalization between Jumpy CS and LC3 but not Atg12, blue arrow indicates colocalization between Jumpy CS and Atg12 but not LC3.",
    "ncbi_link": "LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(S-ZA) C2C12 cells were transfected for 24 h with Jumpy CS and Cherry‐LC3 (LC3), fixed and immunostained with anti‐lamp1. Jumpy CS (green), LC3 (red) and Lamp1 (white in T, X or blue in V, ZA). Boxed areas (S-V) are shown at higher magnification in the corresponding panel below (W-ZA). Yellow arrows indicate colocalization between Jumpy CS and LC3 but not Lamp1. Scale bars, 2 μm.",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(A-C) C2C12 were transfected for 48 h with Jumpy siRNA, followed by a second transfection overnight with Jumpy siRNA and GFP‐WIPI‐1, incubated for 4 h in starvation media, fixed and immunostained with anti‐Atg16 antibody (red). GFP‐WIPI1‐transfected cell (A), endogenous Atg16 immunostaining (B), colocalization of GFP‐WIPI‐1 and Atg16 is indicated in yellow in merge image (C). Boxed areas are shown at higher magnification as inset. Scale bars, 10 and 5 μm in insets.",
    "ncbi_link": "Jumpy: 97287
WIPI‐1: 52639"
  },
  {
    "caption": "(D-I) C2C12 cells were transfected for 48 h with control (scramble) (D, E) or Jumpy siRNA (F-H), followed by a second transfection overnight with corresponding siRNA and GFP‐WIPI‐1. Cells were incubated for 4 h in full (D, G) or starvation media (E, F, H) in presence (F) or absence (E-H) of 100 nM wortmannin, fixed and analysed by confocal fluorescence microscopy. Quantitation of WIPI‐1 puncta per cell (I). Bars, s.e.m. (n=3 independent experiments, with an average of 30 cells per experiment). *P0.05, **P0.01 (t‐test).",
    "ncbi_link": "Jumpy: 97287
WIPI‐1: 52639"
  },
  {
    "caption": "(A-T) C2C12 cells were transfected for 24 h with GFP, GFP‐Jumpy WT or GFP‐Jumpy C330S (Jumpy CS) and Tomato‐LC3 (LC3) and HA‐Atg9, fixed and immunostained with anti‐HA. GFP (I), Jumpy WT (M), Jumpy CS (green) (A, E, Q), LC3 (red) (C, G, J, N, R) and Atg9 (white in B, F, K, O, S or blue in D, H, I, P, T). Boxed areas (A-D) are shown at higher magnification in the corresponding panel below (E-H). White arrows indicate colocalization between Jumpy CS, LC3 and Atg9, blue arrow indicates colocalization between Jumpy CS and Atg9 but not LC3 and yellow arrow indicates colocalization between Jumpy CS and LC3 but not Atg9. White boxes (I-T) show LC3 puncta location. Scale bars, 5 μm.",
    "ncbi_link": "Atg9: 245860
LC3: 67443///66734
Jumpy: 97287"
  },
  {
    "caption": "(U) Percentage of LC3 puncta colocalizing with Atg9. n, number of puncta counted.",
    "ncbi_link": "Atg9: 245860"
  },
  {
    "caption": "(A-K) C2C12 cells were transfected for 48 h with YFP, YFP‐Jumpy WT (Jumpy WT), YFP‐Jumpy C330S (Jumpy CS), YFP‐Jumpy Y462C (Jumpy YC) or YFP‐Jumpy R336Q (Jumpy RQ), fixed and immunostained with anti‐p62 antibody (red). p62 puncta were quantitated by confocal fluorescence microscopy. Representative confocal images of YFP (A), YFP‐Jumpy WT (B), YFP‐Jumpy C330S (C), YFP‐Jumpy Y462C (D) and YFP‐Jumpy R336Q (E) transfected cells, immunostained for p62 (F), (G), (H), (I) and (J), respectively. Scale bars, 5 μm. Quantitation of p62 puncta per cell (K). Bars, s.e.m. (n=3 independent experiments, 30 cells per experiments). *P0.05 (t‐test), ns: nonsignificant.",
    "ncbi_link": "Jumpy: 97287"
  },
  {
    "caption": "(L) HeLa cells were transfected for 24 h with YFP, YFP‐Jumpy WT (Jumpy WT) or YFP‐Jumpy R336Q (Jumpy RQ), incubated with or without 50 ng/μl rapamycin (BafA1 (100 nM) was present in both control and rapamycin treated cells) for 2 h, lysed and analysed for LC3, YFP and actin by immunoblotting. Densitometric LC3‐II/actin ratios are shown underneath the blot.",
    "ncbi_link": "Jumpy: 64419"
  },
  {
    "caption": "Mapping of open chromatin as well as active and repressive histone modifications at upstream regulatory regions of the Prdm1 locus in pro-B cells and plasmablasts. Open chromatin was determined by ATAC-seq (Buenrostro et al., 2013), and active (H3K4me2, H3K4me3, H3K9ac) and repressive (H3K27me3) histone marks were mapped by ChIP-seq analysis in ex vivo sorted pro-B cells (ATAC-seq and H3K27me3, this study), short-term in vitro cultured pro-B cells (H3K4me2, H3K4me3, H3K9ac) (Revilla-i-Domingo et al., 2012) and in vitro LPS-induced plasmablasts (Minnich et al., 2016) (Table EV4). The indicated upstream regions were previously shown by 3C-analysis to interact with the Prdm1 promoter (Wöhner et al., 2016). The mm9 genomic coordinates of mouse chromosome 10 and the respective positions of two human SNPs (rs658431 and rs548234) are indicated. RPM, reads per million mapped sequence reads",
    "ncbi_link": "Prdm1: 12142"
  },
  {
    "caption": "Mapping of nascent transcripts or mature mRNA at the Prdm1 and Atg5 loci by GRO-seq or RNA-seq analyses of ex vivo sorted pro-B and FO B cells, respectively (Table EV4). Strand-specific GRO-seq reads are indicated in blue and red, respectively Quantification of nascent transcript and mRNA levels. The nascent transcription or mRNA expression of the Atg5 and Prdm1 genes is shown as mean expression value (TPM) with SEM based on two different GRO-seq or RNA-seq experiments for each B cell type, respectively. TPM, transcripts per million (Wagner et al., 2012)",
    "ncbi_link": "Atg5: 11793
Prdm1: 12142"
  },
  {
    "caption": "Expression of Prdm1 and Atg5 mRNA in ex vivo sorted pro-B and pre-B cells from the bone marrow of Prdm1ihCd2/+ or wild-type (WT) mice. mRNA expression is shown as mean expression value (TPM) with SEM based on two independent RNA-seq experiments for each cell type and genotype",
    "ncbi_link": "Atg5: 11793
ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "RT-qPCR analysis of nascent Prdm1 and Atg5 transcripts in ex vivo sorted pre-B cells and in in vitro differentiated plasmablasts (PB) of the indicated genotypes. Plasmablasts were generated by stimulation of splenic FO B cells for 4 days with LPS. The data were normalized to those of the ubiquitously expressed control gene Tbp and are presented relative to those of the wild-type pre-B cells (set as 1). Nascent transcripts were PCR-amplified with primers located in the indicated introns (Table EV3). Statistical data are shown as mean value with SEM and were analyzed by the Student"s t-test; *P < 0.05, **P < 0.01. Each dot corresponds to one",
    "ncbi_link": "Atg5: 11793
Prdm1: 12142
Tbp: 21374"
  },
  {
    "caption": "Flow cytometric analysis of hCD2 cell surface expression and intracellular Blimp1 expression of the indicated cell types. Bone marrow of Prdm1ihCd2/+ (red) or wild-type (WT, gray) mice was used to analyz ALPs, BLPs, pro-B, pre-B, immature B cells whereas the spleen was used for flow cytometric analysis o FO B, MZ B and plasma cell of both genotypes The histograms show hCD2 (top row) and Blimp1 (bottom row) expression for the different cell types Wild-type FO B cells (dashed line) were used as negative control for the Blimp1 staining in plasma cells. The difference in mean fluorescence intensity (ΔMFI) between the two genotypes is shown for each cell type",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of hCD2 cell surface expression and intracellular Blimp1 expression of the indicated cell types. Bone marrow of Prdm1ihCd2/+ (red) or wild-type (WT, gray) mice was used to analyz NK cells and granulocytes, whereas the spleen was used for flow cytometric analysis o naïve CD4 T and naïve CD8 T cells of both genotypes The histograms show hCD2 (top row) and Blimp1 (bottom row) expression for the different cell types The difference in mean fluorescence intensity (ΔMFI) between the two genotypes is shown for each cell type",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Immunoblot analysis of Blimp1 and the TATA-binding protein (TBP) in nuclear extracts prepared from short-term cultured wild-type or Prdm1ihCd2/+ pro-B cells. Marker proteins of the indicated size (in kilodaltons) are shown to the right",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of total B cells (A) as well as pro-B, pre-B, immature (imm) B and recirculating (recirc) B cells (B) from the bone marrow of wild-type (WT, gray), Prdm1ihCd2/+ (red) and Prdm1ihCd2/ihCd2 (white) mice at the age of 6-8 weeks Flow cytometric analysis of total B, FO B and MZ B cells from the spleens of wild-type, Prdm1ihCd2/+ and Prdm1ihCd2/ihCd2 mice",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Determination of cell death of ex vivo pro-B and pre-B cells from the bone marrow of Prdm1ihCd2/+ (red) and wild-type (gray) mice by flow cytometric analysis of the loss of plasma membrane asymmetry (F2N12S ratiometric dye staining) and the loss of cell membrane integrity (SYTOX staining). Representative flow cytometry plots (left) and the quantification of dead and apoptotic (apop) cells (right) are shown",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "BrdU labeling of immature (imm) and FO B cells in the spleen of 3-month-old Prdm1ihCd2/+ mice (red dots) and control wild-type littermates (gray dots). The percentage of BrdU+ B cells was determined for each B cell type by flow cytometric analysis after 10 days of continuous BrdU labeling (day 10, white bar) or after a subsequent 15-day chase period (day 25; hatched bar) without BrdU in the drinking wate",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "BrdU labeling of immature (imm) and FO B cells in the spleen of 3-month-old Prdm1ihCd2/+ mice (red dots) and control wild-type littermates (gray dots) A diagram (below) indicates the design of the BrdU labeling and chase experiments. Flow cytometric data obtained with FO B cells from one mouse of each genotype are shown in (F) The percentage of BrdU+ FO B cells is shown above the indicated gates (F)",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Scatter plot of gene expression differences in ex vivo sorted Prdm1ihCd2/+ and wild-type (WT) pro-B (A) and pre-B (B) cells, based on two RNA-seq experiments for each cell type and genotype. The expression data of individual genes (indicated by dots) were plotted as normalized (norm) rlog values. Genes with an expression difference of > 3-fold, an adjusted P value of < 0.05 and a TPM value of > 5 (in one of the two pro-B or pre-B cell types, respectively) are colored in blue or red, corresponding to activation or repression by Blimp1. (C) Expression of commonly activated (blue) and commonly repressed (red) genes in pro-B and pre-B cells. The log2-fold expression change observed between Prdm1ihCd2/+ and wild-type pro-B cells (horizontal axis) as well as between Prdm1ihCd2/+ and wild-type pre-B cells (vertical axis) is plotted for each gene. Lines indicated 2-fold (2x) and 3-fold (3x) expression differences",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Identification of 762 Blimp1 peaks in short-term cultured Prdm1ihCd2/+ pro-B cells, as detected by ChIP-seq with an anti-V5 antibody and MACS peak calling with a P value of < 10-10. The 9320 Blimp1 peaks identified in plasmablasts (PB; Minnich et al., 2016) are shown for comparison. Common (black) and unique (white) peaks are shown for both cell types Densities of Blimp1 binding. Average read density profiles aligned at the center of the Blimp1 peak are shown for the common Blimp peaks of both cell types",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Blimp1 binding at activated and repressed genes in Prdm1ihCd2/+ pro-B and pre-B cells. Regulated genes, which are bound by Blimp1 in Prdm1ihCd2/+ pro-B cells, are shown in black",
    "ncbi_link": "hCd2: 914
ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Blimp1 binding and regulation of the commonly repressed target genes Sell (CD62L) and B3gnt5. The ChIP-seq data (left) were obtained with Prdm1ihCd2/+ pro-B cells (this study) and Prdm1Bio/Bio Rosa26BirA/BirA plasmablasts (PB; Minnich et al., 2016). The RNA-seq data (right) were determined in pro-B and pre-B cells of the Prdm1ihCd2/+ (red) and wild-type (gray) genotype and in Blimp1-deficient (Prdm1Gfp/∆, blue) and wild-type (grey) pre-plasmablasts (Pre-PB; Minnich et al., 2016). Cell types expressing Blimp1 (+) are indicated",
    "ncbi_link": "B3gnt5: 108105
ihCd2: 914
Prdm1: 12142
CD62L: 20343
Sell: 20343"
  },
  {
    "caption": "Expression of selected Blimp1-activated and Blimp1-repressed genes coding for transcriptional regulators (H) and intracellular signal transducer in Prdm1ihCd2/+ (red) and wild-type (gray) pre-B cells. Blimp1-bound genes are underlined. The mRNA expression of the indicated genes is shown as mean expression value (TPM) with SEM, based on two different RNA-seq experiments for pre-B cells of each genotype",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of plasma cells from the spleen (A) and bone marrow (B) of Prdm1ihCd2/+ and wild-type (WT) mice under steady-state conditions. Representative flow cytometric data are shown for 12-month-old mice (left), while bar graphs present absolute numbers of plasma cells for Prdm1ihCd2/+ (red) and wild-type (gray) mice at the age of 2, 4 and 12 months (right)",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "T cell-dependent immune responses. Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice at the age of 2 months were immunized with NP-KLH (in alum) and analyzed at day 14 after immunization by ELISPOT assa The number of anti-NP-IgM antibody-secreting cells (ASCs) in the spleen was determined by ELISPOT assay (C) using NP24-BSA-coated plates for detecting cells secreting total anti-NP-IgM antibodies. ELISPOT results are shown as representative pictures (left) or absolute ASC numbers (right) (C) Dot plots display the serum immunoglobulin titers of Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice NP-specific IgG1 concentrations (μg/ml) were determined relative to a standard NP-binding IgG1 antibody",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "T cell-dependent immune responses. Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice at the age of 2 months were immunized with NP-KLH (in alum) and analyzed at day 14 after immunization b ELISA The serum titers of anti-NP-specific IgM, IgG1 and IgG2b antibodies were analyzed by ELISA using NP7-BSA- or NP24-BSA-coated plates for detecting high-affinity IgG1 or total IgM, IgG1 and IgG2b antibodies, respectivel Dot plots display the serum immunoglobulin titers of Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice. NP-specific IgG1 concentrations (μg/ml) were determined relative to a standard NP-binding IgG1 antibody, whereas IgM and IgG2b amounts are indicated as relative units (RU) by setting the WT data to 1",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of splenic GC B cells in Prdm1ihCd2/+ (red) and wild-type (gray) mice (at the age of 2 months) at day 14 after NP-KLH immunization. Bar graphs display absolute numbers of GC B cells detected in the spleen of both genotype The absence of Bcl6 expression in non-GC B cells (black) is shown as reference",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of splenic GC B cells in Prdm1ihCd2/+ (red) and wild-type (gray) mice (at the age of 2 months) at day 14 after NP-KLH immunization Cell surface expression of hCD2 and intracellular staining of Bcl6 are shown for Prdm1ihCd2/+ (red) and wild-type (gray) GC B cell The absence of Bcl6 expression in non-GC B cells (black) is shown as reference",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysi in Prdm1ihCd2/+ (red) and wild-type (gray) mice (at the age of 2 months) at day 14 after NP-KLH immunization Flow cytometric analysis of splenic TFH cell Bar graphs indicate absolute numbers of TFH cell in hCD2lo (black) and hCD2hi (blue) Prdm1ihCd2/+ as well as wild-type (gray) TFH cells",
    "ncbi_link": "hCD2: 914
ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysi in Prdm1ihCd2/+ (red) and wild-type (gray) mice (at the age of 2 months) at day 14 after NP-KLH immunization Flow cytometric analysis of splenic TFH cell histograms display cell surface expression of hCD2 and intracellular staining of Bcl6 (H) in hCD2lo (black) and hCD2hi (blue) Prdm1ihCd2/+ as well as wild-type (gray) TFH cells",
    "ncbi_link": "hCD2: 914
ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Efficient in vitro plasmablast differentiation of immature B cells. Immature B cells sorted from the bone marrow of Prdm1ihCd2/+ (red) and wild-type (gray) mice were stimulated with CpG oligodeoxynucleotides or LPS for 60 hours followed by flow cytometric analysis of CD138+CD22lo plasmablasts (PB). Bar graphs (right) summarize the plasmablast data of the CpG and LPS stimulation experiments",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "Flow cytometric analysis of total B cells and different B cell subsets in the bone marrow of non-immunized Eβ-/- Prdm1ihCd2/+ (red) and Eβ-/- Prdm1+/+ (gray) chimeric mice. Bar graphs indicate absolute numbers of the different B cell types in these chimeric mice",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142
Eβ: 21577"
  },
  {
    "caption": "Flow cytometric analysis of total B cells and different B cell subsets in th splee of non-immunized Eβ-/- Prdm1ihCd2/+ (red) and Eβ-/- Prdm1+/+ (gray) chimeric mice. Bar graphs indicate absolute numbers of the different B cell types in these chimeric mice Histograms display the expression of hCD2 (Blimp1) in splenic FO B, GC B and naïve CD4 T cells from the chimeric mice of the indicated genotypes",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142
Eβ: 21577"
  },
  {
    "caption": "Presence of IgG antibodies detecting dsDNA, cardiolipin, SSA (Ro-52) and SSB (La) in the serum of Prdm1ihCd2/+ (red dots) and wild-type (gray dots) mice at the age of 2, 4 and 12 months. The titers of the different IgG antibodies were determined in the serum of male and female mice by ELISA and are displayed as arbitrary units (AU). The serum of 6-month-old Faslgld/gld mice was used as positive control",
    "ncbi_link": "ihCd2: 914
Fasl: 14103
Prdm1: 12142"
  },
  {
    "caption": "Representative images of anti-nuclear antibody (ANA) staining obtained with serum from 12-month-old Prdm1ihCd2/+ or wild-type mice (right), as detected by indirect immunofluorescence assay using HEp-2 cells and an Alexa488-conjugated anti-mouse IgG detection antibody. The serum of Faslgld/gld mice was used as positive control. The presence of ANA-IgG antibodies was analyzed for 22 Prdm1ihCd2/+ and 12 wild-type mice, as summarized in the pie-chart (right)",
    "ncbi_link": "ihCd2: 914
Fasl: 14103
Prdm1: 12142"
  },
  {
    "caption": "Periodic acid-Schiff (PAS) staining of paraffin-embedded kidney sections of Prdm1ihCd2/+ and wild-type mice at 12 months of age. The mean score of kidney pathology was determined for each mouse by evaluating 40 individual glomeruli to assess the severity of glomerulonephritis as shown in Table EV2 and described in the Appendix Supplementary Methods. Representative pictures of glomeruli of Prdm1ihCd2/+ kidneys with different pathology scores are shown to the left, and dot plots with average scores for male and female mice (Table EV2) are shown to the right. Arrows denote intracapillary hyaline "thrombi", asterisks indicate mesangial sclerosis with obscured capillary loops, and the arrowhead points to an obsolescent glomerulus with collapse of the glomerular tuft architecture. Statistical data (A,C) are shown as mean value with SEM and were analyzed by the Mann-Whitney test (A) or the Student"s t-test (C); *P < 0.05, **P < 0.01, ***P < 0.001. Each dot correspon",
    "ncbi_link": "ihCd2: 914
Prdm1: 12142"
  },
  {
    "caption": "b. Mitophagy time course. Representative photomicrographs  showing time course of DFP treatment in mitophagy  reporter cells (human ARPE-19 cells with stable expression of  mito-QC). Mitochondrial networks are visible in yellow and mitolysosomes as red-only puncta signifying mitophagy. Nuclei are counterstained with Hoescht33342. Mitophagy  appears maximal after 24 h of DFP treatment, with little difference between control and 7 h conditions. Inset shows details of mitolysosomes within the mitochondrial network of a highly mitophagic  cell following DFP treatment. Arrows highlight mitolysosomes. Scale bar = 5 μm.",
    "ncbi_link": "mito-QC: "
  },
  {
    "caption": "a. ARPE-19 ULK1 CRISPR  KO cells with/without re-introduction of FLAG-ULK1 were treated with DFP  for 24h as indicated. Cells were fixed and stained  with  BODIPY493/503 to visualise  lipid droplets (green) or DAPI to visualise nuclei (blue). Scale bar, 10 μm.",
    "ncbi_link": "CRISPR: 
FLAG: 
ULK1: 8408"
  },
  {
    "caption": "c. Representative photomicrographs  of larval neuronal cell bodies  expressing the matrix-QC reporter and RNAi for mdy or control driven with nSyb-GAL4. GFP is shown in green, mCherry  is shown in magenta.  Mitolysosomes (mCherry-only puncta) are shown in greyscale. Scale bar = 5 μm.",
    "ncbi_link": "matrix-QC: 
GAL4: 855828
mdy: 44887
Syb: 36080"
  },
  {
    "caption": "Transduction of HSCs. B. Lower numbers of GFP+ cells, verified using flow cytometry, after transduction with Sema3F vector, ***p<0.0001, Student t test, n=8 independent experiments.",
    "ncbi_link": "Sema3F: 6405"
  },
  {
    "caption": "Transduction of HSCs. C. Western blot showing GFP expression in cells transduced with both vectors and Sema3F expression in the supernatant of Sema3F-transduced cells only.",
    "ncbi_link": "Sema3F: 6405"
  },
  {
    "caption": "Expression of Nrp2 gene by OPCs is maintained in middle-age (12 month (m) old) mice. A. Microarray analyses results for Nrp2 expression by OPCs purified using FACS from the brains of 2 months versus 12 months old PDGFRα−GFP mice (n=3-4 independent experiments).",
    "ncbi_link": "GFP: 
Nrp2: 18187
PDGFRα: 18595"
  },
  {
    "caption": "Expression of Nrp2 gene by OPCs is maintained in middle-age (12 month (m) old) mice. B. RNA sequencing results for Nrp2 expression by oligodendroglia-enriched preparations isolated from the spinal cords of 2 month versus 12 month old mice. (n=3-4 independent experiments).",
    "ncbi_link": "Nrp2: 18187"
  },
  {
    "caption": "D. Percentages of GFP+ cells labeled with CD11b, CD19, and CD3. The proportion of GFP+ cells labeled with CD11b is increased in Sema3F mice (p=0.01), while that of CD19-labeled cells is decreased (p=0.0003). Mean±SEM. Unpaired Student t-test. n=9 mice/group. *p<0.05,***p<0.001.",
    "ncbi_link": "Sema3F: 6405"
  },
  {
    "caption": "A-F. Co-labeling for GFP and MBP on spinal cord sections of GFP (A-C) and Sema3F-GFP chimeras (D-F) sacrificed at 7 (A,D), 10 (B,E), and 60 (C,F) days post lesion (dpl). Absence of MBP labeling in A-B,D-E indicates the lesion (delimited by yellow lines). Areas faintly labeled with MBP in C-F likely represent remyelinated areas.",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "G. Quantification of GFP+ cells. Kruskal-Wallis test p=0.02. No significant differences between GFP and Sema3F at any of the time points (Dunn's post test; Mann-Whitney test). Decrease in GFP+ cells between 7 and 60 dpl for both GFP and Sema3F mice 2m.",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "U. Quantification of Iba1+, CD3+, and B220+ cells. For all 3 populations, no significant differences in cell numbers were observed between GFP and Sema3F mice, and a general decrease was observed at 60 dpl compared to earlier time points.",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "B-G. Lesions at 7 dpl in GFP (B,E) and Sema3F (C,F) mice. B-C. Co-labeling for PDGFRα, MBP, and DAPI. Arrows indicate OPCs in the lesion. Bi and Ci-insets of white dotted squares in B and C. D. Higher numbers of PDGFRα+ (OPCs) cells in Sema3F mice at 7 dpl (Mann Whitney test: p=0.0031, n=6-8 mice/group). E-F. Co-labeling for Olig2 and MBP. E'-F'. Co-labeling for Olig2 and GFP of the lesions shown in E-F. 3D reconstructions. Proximity of OPCs and Sema 3F-carrying cells. E'i-E'iii and F'i-F'iii-insets of E'-F'. G. Higher numbers of Olig2+ (oligodendroglial) cells in Sema3F-GFP mice at 7 dpl (Mann Whitney test: p=0.0047, n=5-8 mice/group).",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "H-I. Immunolabelling for activated OPC marker Nkx2.2. J. Numbers of Nkx2.2+ cells are increased in lesions of Sema3F-GFP mice at 7dpl (Mann Whitney test: p=0.014, n=6-7 mice/group). Arrows indicate Nkx2.2+ cells in close proximity of GFP+ cells.",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "K-P. colabelling for Nkx2.2 and proliferation marker Ki67. Arrows indicate double labeled cells. Q. Numbers of Nkx2.2+Ki67+ cells are increased at 7 dpl in Sema3F-GFP mice. Mean±SEM. n=6-7 mice/group. R. The proportion of Nkx2.2+ cells co-expressing Ki67 is unchanged. Mean±SEM. n=6-7 mice/group.",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "A-B. Labelling for APC/CC1, a marker of oligodendrocytes. Dotted lines indicate the lesion border. APC+ cells are scarce in the lesions of GFP mice (A). B. APC+ cells in the lesion of Sema3F mice. C. Quantification of APC+ cells (Mann Whitney test; p=0.0061 for 7 dpl, p=0.0081 for 10 dpl; n= 6-7 mice/group).",
    "ncbi_link": "GFP: 
Sema3F: 6405"
  },
  {
    "caption": "D-E. EM images of the lesion in GFP (D) and Sema3F (E) chimeras at 14 dpl. Thin myelin sheaths in Sema 3F mice (yellow arrows). F. Higher power image of a new myelin sheath in a Sema3F mouse. Fi. Inset of yellow square in F. G. Quantification of remyelinated axons (Mann Whitney test: p=0.03, n=6 mice/group). *p<0.05. H. In Sema3F mice, oligodendroglial cells (O) and early remyelination (*) are frequently observed in macrophage (M) vicinity. Hi. Inset of yellow dashed square in H.",
    "ncbi_link": "GFP: 
Sema 3F: 6405
Sema3F: 6405"
  },
  {
    "caption": "Impact of MB on cytotoxicity of OT-1 CTLs against EG7 or EG7-L1. Splenocytes from OT-1 mice in culture were stimulated with 10 nM of OVA257-264 (SIINFEKL) for 3 days to generate mature CTLs. CTLs were incubated with CFSE labeled EG7-L1 cells in the presence of MB at indicated concentrations. Cytotoxicity was determined by flow cytometry analysis. Data are representative of three independent experiments. (effector to target ratio = 5:1, unpaired t-test). EG7-L1: EG7 overexpressing PD-L1.   Statistical results of (B).   ELISA measured of LDH release to assess the cytotoxicity of OT-I CTLs on EG7-L1 in the presence of MB. Anti-PD1 antibody (aPD-1) served as positive control.   Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. **P < 0.01; ***P < 0.001; ****P < 0.0001.",
    "ncbi_link": "L1: 60533
PD-L1: 60533"
  },
  {
    "caption": "Impact of MB on cytotoxicity of PD-1-/- (PD-1KO) OT-1 CTLs against EG7 or PD-L1 expressing EG7 stable cell line. Data are representative of three independent experiments. (unpaired t-test). Statistical results of (E). Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. **P < 0.01; ***P < 0.001; ****P < 0.0001.",
    "ncbi_link": "PD-L1: 60533
PD-1: 18566"
  },
  {
    "caption": " Effect of MB on the proliferation of WT CTLs, PD-1KO CTLs. Splenic cells were stained with 5 μM of CFSE and seeded into aCD3/aCD28 coated 96-well plates. 10 μg/ml of PD-L1 were administered in media. Cell proliferation were checked by monitoring dilution of CFSE 48 hours after CD3/CD28 stimulation by gating on CD8 positive population through FACS analysis. WT: splenic cell from wildtype C57BL/J mice. PD-1KO: splenic cell from PD-1 knockout mice.   Statistical results of (A)   Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 ",
    "ncbi_link": "PD-1: 18566"
  },
  {
    "caption": " Effect of MB on the activation status of Jurkat T cells. Luciferase activity is suppressed in JP-luc by co-culture with Raji-L1 preloaded with 1 μg/ml superantigen (SEE). Treatment with MB enhanced luciferase expression (SEE-Loaded Raji (PD-L1 negative) served as positive control). IC50 is calculated to be 117 nM. JP-luc: Jurkat cell harboring NFAT-luciferase transgene and overexpressing PD-1; Raji-L1: Raji overexpressing PD-L1 Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 ",
    "ncbi_link": "luc: 
luciferase: 
L1: 29126
PD-L1: 29126
PD-L1: 60533
PD-1: 5133"
  },
  {
    "caption": " Impact of MB on luciferase activity of various engineered Jurkat T cells. J-luc: Jurkat cell harboring NFAT-luciferase transgene; J-luc-sgPD-1: J-luc cells treated with lentivirus expressing sgPD-1/CAS9 simultaneously Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 ",
    "ncbi_link": "CAS9: 
luc: 
luciferase: 
PD-1: 5133"
  },
  {
    "caption": " qRT-PCR analysis of IL-2 mRNA level in JP-luc cells stimulated with precoated aCD3/aCD28 (10 μg/ml) in the presence of 10 μg/ml of PD-L1 and MB at indicated concentrations Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 ",
    "ncbi_link": "luc: 
IL-2: 3558"
  },
  {
    "caption": " MB enhancing IL-2 expression by JP-luc stimulated with Raji-L1 for 24-hour quantified through ELISA analysis (aPD1 served as positive control).   MB enhancing production of cytokine and cytolytic granule by OT-I CTLs. CTLs were incubated with EG7-L1 cells in the presence of protein transport inhibitor (PTI) and MB at indicated concentrations. Expression of cytokine and cytolytic granule were determined by flow cytometry. aPD1 served as positive control. EG7-L1: EG7 overexpressing PD-L1.   Statistical results of (I)   Data information: Data are representative of three independent experiments. Unpaired t-test; Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 ",
    "ncbi_link": "luc: 
L1: 29126
L1: 60533
PD-L1: 60533"
  },
  {
    "caption": " Fluorescence complementation analysis of the effect of MB on the interaction between PD-1 with SHP2. Jurkat cells co-expressing PD1-C-Luc or PD1Y248F-C-Luc and SHP2-N-luc were seeded in a 96-well precoated with 10 μg/ml of aCD3/aCD28 with media supplemented with 10 μg/ml human PD-L1 protein in the presenc of MB at indicated concentrations for 6 hours followed by analysis of luciferase activity Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. *P < 0.05; **P < 0.01; ****P < 0.0001 ",
    "ncbi_link": "Luc: 
luc: 
PD1: 5133
SHP2: 5781"
  },
  {
    "caption": " Representative western blot showing the levels CD28 phosphorylation. CTL were stimulated with EG7 cells (parental), EG7-L1 and EG7-L1 in the presence 100 nM of MB for 2 hours. Protein immunoprecipitated (IP) with Anti-pY from the lysates of the indicated CTL-EG7 co-culture were subjected to SDS-PAGE separation and blotted with aCD28. β-actin served as loading control. EG7-L1: EG7 overexpressing PD-L1 Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. *P < 0.05; **P < 0.01; ****P < 0.0001 ",
    "ncbi_link": "L1: 60533
PD-L1: 60533"
  },
  {
    "caption": " Phos-tag analysis of CD28 phosphorylation in CTL. CTLs were stimulated with EG7 or EG7-L1 in the presence of 1μΜ MB. Cell lysate were then separated by SDS-PAGE containing 50 μM of Phos-tag and blotted with aCD2 antibody. Phosphorylated CD28 (slow-moving) species were visualized through exposure",
    "ncbi_link": "L1: 60533"
  },
  {
    "caption": " Fluorescence complementation analysis of the effect of MB on the interaction between CD28 with P85. Jurkat or Jurkat-PD-1 cells were co-transfected with CD28-C-Luc or CD28Y191F-C-Luc and P85-N-Luc. Cells were seeded in a 96-well plate coated with 10 μg/ml of aCD3/aCD28 in the presence of human 10 μg/ml of PD-L1 protein and 100 nM of MB for 6 hours. Luciferase activity was measured as readout for CD28-P85 interaction Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. *P < 0.05; **P < 0.01; ****P < 0.0001 ",
    "ncbi_link": "Luc: 
CD28: 940
PD-1: 5133
P85: 5296///5295"
  },
  {
    "caption": "Schematic of the xenograft mouse model for MB treatment. C57BL/6J mice were inoculated with EG7-L1 cells (2 × 106 cells, s.c.) on the right flank on day 1, followed by injection (2 × 106 cells, i.v.) of CD45.1+ CTL on day 3 and day 6 respectively. The mice were randomized into 3 groups (n = 5) and treated with vehicle, MB (20 mg/kg/day, i.g.), aPD1 (10 mg/kg, every other day, i.p.) served as positive control. Tumor size was measured through calipering every other day. EG7-L1: EG7 overexpressing PD-L1.   Tumor growth curve for (A) was shown as mean ±s.e.m.   Representative image of the tumor on day 10 mentioned in (A).   Tumor weight on day 10 (n=5) mentioned in (A).   Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.",
    "ncbi_link": "L1: 60533
PD-L1: 60533"
  },
  {
    "caption": "Schematic of EGFR L858R mice treated with MB.   Tumor burdens recorded through Computed tomography (CT) scanning for EGFR L858R mice (n=5, lung section = 3). Mice were treated with MB (20 mg/kg/day, i.g.) for 1 week, followed by imaged with CT again to record tumor burden.   Statistical results of (J).   Haematoxylin and Eosin staining of lung section of EGFR L858R mice (n = 5, lung section = 3) in (J).   Statistical results of (L).   Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "Comparison of the efficacy of MB with PD1 inhibitors currently used in clinic to activate T cell. JP-luc cells were stimulated with Raji-L1 or parental Raji cells preloaded with 1 μg/ml of superantigen (SEE) in the presence of MB at indicated concentration or 25μg/ml of pembrolizumab (Pem) or 20μg/ml of nivolumab (Niv) for 6 hours. Luciferase activity was measured by luminometer. Data are representative of three independent experiments, and were analyzed by unpaired t-test. JP-luc: Jurkat cell harboring NFAT-luciferase transgene and overexpressing PD-1; Raji-L1: Raji overexpressing PD-L1. Data information: Data are representative of three independent experiments, and were analyzed by unpaired t-test. Error bars denote s.e.m. **P < 0.01; ****P < 0.0001. ",
    "ncbi_link": "luc: 
luciferase: 
L1: 29126
PD-L1: 29126
PD-1: 5133"
  },
  {
    "caption": "(D) WT and AMPKα1-/- BMDMs  were treated with Dex  for 1 h before analysis by  western blot  and GR phosphorylation  at S211 was quantified. Data information: results are means ± SEM or z-score or displayed with boxes and whiskers in which the central band represents the median. N= 3 (D) biological replicates * p<0.05, ** p<0.01, *** p<0.001 statistical analysis using ANOVA tests (D,",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "(E) WT and AMPKα1-/- BMDMs  were treated with Dex  for 24 h and analyzed by  RNA-seq. Differentially expressed genes between any condition were clustered using c-means clustering.",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "(F) WT and AMPKα1-/- BMDMs  were treated with Dex  for 24 h and anti-/pro-inflammatory markers assessed using immunofluorescence. Data information: results are means ± SEM or z-score or displayed with boxes and whiskers in which the central band represents the median. N= 3-4 (F) biological replicates",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "(G WT and AMPKα1-/- BMDMs  were treated with Dex  for 72 h, washed and conditioned medium was recovered after 24 h used to treat  muscle stem cells. Proliferation  (Ki67 immunostaining) (G) were assessed in muscle stem cells. Data information: results are means ± SEM or z-score or displayed with boxes and whiskers in which the central band represents the median. N= 4 biological replicates (G * p<0.05, ** p<0.01, *** p<0.001 statistical analysis using ANOVA tests Bar=25 µm (G",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "H) WT and AMPKα1-/- BMDMs  were treated with Dex  for 72 h, washed and conditioned medium was recovered after 24 h used to treat muscle stem cells. differentiation  (desmin immunostaining  and counting the percentage of muscle cells  with 2 nuclei or more) (H) were assessed in muscle stem cells. Data information: results are means ± SEM or z-score or displayed with boxes and whiskers in which the central band represents the median. N= 4 biological replicates H). * p<0.05, ** p<0.01, *** p<0.001 statistical analysis using ANOVA tests ,H). Bar=25 µm H).",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "After cardiotoxin  injection to damage the muscle, AMPKα1fl/fl (WT) and LysM-α1-/- mice  were treated with a single dose of Dexamethasone  (Dex) intra-peritoneal (i.p.) (0.1 mg/kg) at day 3 (D3) and Tibialis Anterior  (TA) muscles  were harvested at day 8 (D8) and 14 (D14) after injury. (A) Representative embryonic myosin heavy chain (EmbMHC) immunostaining  on whole TA muscle  section at D8 and D14 after injury. (B) Quantification of (A), results are expressed as percentage of positive myofibers  expressing the EmbMHC  on the whole muscle section. Data information: results are displayed with box and whiskers in which the central band represents the median (B N= 7-12 muscles  (B * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001 using ANOVA tests. Bars = 500 µm (A),",
    "ncbi_link": "LysM: 17105
AMPKα1: 105787
α1: 105787"
  },
  {
    "caption": "(F) Macrophage  polarization was determined by immunofluorescence  in vehicle, DAMPs  and DAMPs+Dex  treated WT and AMPKα1-/- BMDMs. Data information: results are displayed with box and whiskers in which the central band represents the means ± SEM (F). N= 4-5 biological replicates (F). * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001 using ANOVA tests. Bars = 25 µm (F).",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "(F) Macrophage  polarization was determined by immunofluorescence  in vehicle, LPS  and LPS+Dex  treated WT and AMPKα1-/- BMDMs, data are expressed as percentage positive cells. Data information: Results are displayed with box and whiskers in which the central band represents the means ± SEM (F). N= 3 (F) biological replicates. Statistical analysis by ANOVA F) * p<0.05, ** p<0.01, *** p<0.001. Bar = 25 µm (F).",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "(F) WT and AMPKα1-/- Bone Marrow Derived Macrophages (BMDMs) were treated with either Dex  or the AMPK  activator 991  and protein phosphorylated  on serine were immunoprecipitated. Westen-blot for FOXO3, AMPKα1, actin  and the phosphorylated  form of FOXO3  were done. Quantification of the band intensity is provided normalized to those of actin  and total FOXO3, a representative example is shown. Data information: results are box and whiskers in which the central band represents the median F, N= 4-5 (F biological replicates. * p<0.05, ** p<0.01, *** p<0.001 **** p<0.0001 using ANOVA and Kruskal-Wallis tests",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "siRNA-mediated knockdown of PHPT1 in HeLa cells (24 h) with reference to GAPDH loading control. NT - non-targeting siRNA control.",
    "ncbi_link": "PHPT1: 29085"
  },
  {
    "caption": "Representative SAX profile of trypsin digested HeLa lysate (Abs280 nm). Base peak chromatograms are shown for select SAX fractions following high-resolution LC-MS/MS using an Orbitrap Fusion mass spectrometer: (D) fraction 3 (green); (E) fraction 6 (red); (F) fraction 10 (grey). Peptides were fragmented by HCD, with neutral loss of 98 amu from the precursor ions triggering EThCD (Ferries et al, 2017). Tandem mass spectra were separated according to fragmentation strategy in Proteome Discoverer prior to searching with Mascot. The ptmRS node was used for phosphosite localisation. Analysis was performed on three independent biological replicates for each condition (NT or PHPT1 siRNA).",
    "ncbi_link": "PHPT1: 29085"
  },
  {
    "caption": "D-F.  Immunofluorescence images of the midgut section from the R4 region in Drosophila carrying esgts-GAL4-driven  UAS-lacZ  (D, control), Las RNAi (E), or Las  RNAi in response to ALA  administration (F). esg-GFP (green) indicates ISCs and their differentiating cells. Dl staining (red) was used to visualize ISCs. Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "lacZ: 
GAL4: 
esg: 34903
Las: 40259"
  },
  {
    "caption": "I-J. Immunofluorescence  images of control (FRT40A, I) and  Las RNAi (J) MARCM clones (green, outlined by white dotted lines) 10 days after clone induction (ACI). Pdm1 staining (red) was used to visualize ECs. K. Quantification of the ratio of Pdm1+ cells per clone of  MARCM clones with indicated genotypes. n is indicated. Each dot corresponds to one clone. L. Quantification of  MARCM clone size of experiments in (I-J). n is indicated. Each dot corresponds to one clone. Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 10 μm (D Error bars represent SDs. Student's t-tests, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "FRT40A: 
Las: 40259"
  },
  {
    "caption": "A-F. Immunofluorescence images of midgut  sections from the R4 region in Drosophila carrying esgts-GAL4-driven expression of  CAT  cDNA (A), CAT  cDNA with AD4  administration (B), CAT  cDNA with ALA  administration (C), Keap1 RNAi (D), Keap1  RNAi with AD4 administration (E), or Keap1 RNAi with ALA administration (F). esg-GFP (green) represents ISCs and their differentiating cells. Dl staining (red) was used to visualize  ISCs. G. Quantification of the number  of esg-GFP+ cells, Dl+ cells of Drosophila  carrying esgts-GAL4-driven expression of  lacZ  cDNA, CAT  cDNA, CAT  cDNA with AD4  administration, CAT  cDNA with ALA administration, Keap1  RNAi, Keap1  RNAi with AD4 administration, or Keap1 RNAi with ALA administration. n is indicated. The numbers of quantified guts from left to right are 18, 19, 20, 18, 18, 19, 19, 18, 19, 20, 18, 18, 19, and 19. H. Quantification of the number of pH3+ cells and luciferase activity of Drosophila  carrying esgts-GAL4-driven expression of lacZ cDNA, CAT cDNA, CAT cDNA with AD4  administration, CAT cDNA with ALA administration, Keap1 RNAi, Keap1  RNAi with AD4 administration, or Keap1 RNAi with ALA administration. The numbers of quantified  guts from left to right are 18, 19, 20, 18, 18, 19, and 19. I- Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm Error bars represent SDs. Student's t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "GAL4: 
lacZ: 
CAT: 40048
esg: 34903
Keap1: 42062"
  },
  {
    "caption": "I-L. Representative images of the  midgut  section from the R4 region of  Drosophila carrying  esgts-GAL4-driven expression of lacZ cDNA (I),  Las RNAi (J), Las  RNAi and CAT cDNA (K), or Las  RNAi and Keap1  RNAi (L). esg-GFP (green) indicates ISCs and their differentiating cells. Dl staining (red) was used to visualize ISCs. Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "GAL4: 
lacZ: 
CAT: 40048
esg: 34903
Keap1: 42062
Las: 40259"
  },
  {
    "caption": "F-H. Expression of esg-GAL4-driven UAS-GFP-mCherry-Atg8a  in 14-day Drosophila (F), 40-day Drosophila  (G), 40-day Drosophila with  ALA administration started at the middle age (26 days) (H). GFP  (green) and  mCherry (red). The red arrows indicate the autophagosomes. I. Quantification of the dot number  of mCherry in esg positive cells from experiments (F-H). n is indicated. The numbers  of quantified guts from left to right are 11, 10, and 12. J. Quantification of the dot size of mCherry in esg  positive cells from experiments (F-H). n is as indicated. K- Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 2 μm Error bars represent SDs. Student's t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "GAL4: 
esg: 34903"
  },
  {
    "caption": "K-L. Immunofluorescence images of esg-GFP and Lysotracker staining with the midgut  section from the R4 region in 14-day flies carrying esgts-GAL4-driven UAS-lacZ  (K), and 14-day  flies carrying esgts-GAL4-driven  Las RNAi (L). esg-GFP (green; outlined by dotted lines), lysotracker (red). esg-GFP+ cells are outlined by dotted lines. M. Quantification of the dot number of Lysotracker in esg  positive cells from experiments (K-L). n is indicated. The numbers of quantified guts from left to right are 10, and 9. N. Quantification of the dot size of Lysotracker in esg positive cells from experiments (K-L). n is as indicated. O- Data information: DAPI stained nuclei are shown in blue. Scale bars represent 5 μm Error bars represent SDs. Student's t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "lacZ: 
GAL4: 
esg: 34903
Las : 40259"
  },
  {
    "caption": "O-P. Expression of esg-GAL4-driven UAS-GFP-mCherry-Atg8a in 14-day Drosophila carrying esgts-GAL4-driven UAS-lacZ  (flies were cultured at 18 °C and transferred to 29 °C after flies eclosion) (O), and 14-day  Drosophila  with  Las  depleted in ISCs and EBs (flies were cultured at 18 °C and transferred to 29 °C after flies eclosion) (P). GFP (green) and mCherry (red). The red arrows indicate the autophagosomes. Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 2 μm Error bars represent SDs. Student's t-tests, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "lacZ: 
GAL4: 
esg: 34903
Las: 40259"
  },
  {
    "caption": "F-I. Representative images of the midgut  section from the R4 region of Drosophila carrying esgts-GAL4-driven expression of  lacZ  cDNA (F, control), Las RNAi (G),  Las RNAi and  Atg5  cDNA (H), or Las  RNAi with spermidine administration (I). GFP  (green) and Dl staining (red) was used to visualize ISCs. Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "lacZ: 
GAL4: 
Atg5: 31666
esg: 34903
Las : 40259
Las: 40259"
  },
  {
    "caption": "N. Survival  (percentage) of female Drosophila with indicated genotypes. The numbers of quantified Drosophila: 100 (UAS-lacZ), 100 (Las RNAi), 100 (Las RNAi + UAS-Atg5), and 100 (Las RNAi + UAS-Atg8a). Three independent experiments were conducted. Data information: Error bars represent SDs. p-values for lifespan curves (N) were calculated by the log-rank test. The statistical tests used in other panels were student's t-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "lacZ: 
Atg5: 31666
Atg8a: 32001
Las: 40259"
  },
  {
    "caption": "A-E. Expressions of Rab5-GFP reporter in ISCs of 14-day WT Drosophila (A), 40-day WT Drosophila (B), 40-day Drosophila with ALA administration (C), 14-day Drosophila carrying  esgts-GAL4>UAS-lacZ (D), and 14-day Drosophila carrying esgts-GAL4>Las RNAi (E). GFP (green). F. Quantification of fluorescence intensity of RAB5-GFP in experiments (A-E). Each dot corresponds to one cell. n is indicated. The numbers of quantified guts from left to right are 13, 11, 12, 10 and 13. G Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 2 μm Error bars represent SDs. Student's t-tests, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "GAL4: 
lacZ: 
esg: 34903
Las: 40259"
  },
  {
    "caption": "G-K. Expressions of  Rab7-GFP  reporter in ISCs of 14-day WT Drosophila (G), 40-day WT Drosophila (H), 40-day Drosophila with  ALA administration (I), 14-day Drosophila carrying esgts-GAL4>UAS-lacZ (J), and 14-day Drosophila  carrying esgts-GAL4>Las RNAi (K). GFP (green). L. Quantification of fluorescence intensity of  RAB7-GFP  in experiments (G-K). Each dot corresponds to one cell. n is indicated. The numbers of quantified guts from left to right are 11, 10, 11, 13 and 12. M Data information: DAPI stained nuclei  are shown in blue. Scale bars represent 2 μm Error bars represent SDs. Student's t-tests, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "GAL4: 
lacZ: 
esg: 34903
Las: 40259"
  },
  {
    "caption": "M-Q. Immunofluorescence images of midgut section from the R4 region of Drosophila carrying esgts-GAL4-driven expression of lacZ cDNA (M, control), constitutively active form of RAB5 (N), constitutively active form of  RAB5 with ALA  administration (O), constitutively active form of RAB7 (P), or constitutively active form of RAB7 with ALA  administration (Q). GFP  (green) and  Dl staining (red) was used to visualize ISCs. Data information:  DAPI stained nuclei  are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "GAL4: 
lacZ: 
esg: 34903
RAB5: 33418
RAB7: 42841"
  },
  {
    "caption": "A-D. Representative images of midgut sections from the R4 region of Drosophila carrying esgts-GAL4-driven expression of lacZ cDNA (A, control), Las  RNAi (B), Las RNAi and RAB5-CA (C), or Las RNAi and RAB7-CA (D). GFP  (green), Dl staining  (red) was used to visualize  ISCs. Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "GAL4: 
lacZ: 
esg: 34903
Las: 40259
RAB5: 33418
RAB7: 42841"
  },
  {
    "caption": "C. Survival (percentage) of female  Drosophila of indicated genotypes. The numbers of quantified Drosophila: 100 (UAS-lacZ), 100 (Las  RNAi), 100 (Las RNAi + UAS-Rab5-CA) and 100 (Las RNAi + UAS-Rab7-CA). Three independent experiments were conducted Data information: Error bars represent SDs. p-values for lifespan curves (C) were calculated by the log-rank test. The statistical tests used in other panels were student's t-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "lacZ: 
Las: 40259
Rab5: 33418
Rab7: 42841"
  },
  {
    "caption": "F-I. Immunofluorescence images of dpERK staining of midgut sections of the R4 region of 40-day Drosophila (F), 40-day Drosophila with ALA administration (G), 14-day Drosophila carrying esgts-GAL4-driven UAS-lacZ (H), and Drosophila carrying esgts-GAL4-driven Las RNAi (I). dpERK (red). J. Quantification of the fluorescence intensity of dpERK in experiments (F-I). Each dot corresponds to one cell. n is indicated. The numbers of quantified guts from left to right are 11, 12, 12, and 13. K Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm Error bars represent SDs. The statistical tests used in other panels were student's t-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and non-significant (NS) represents p > 0.05.",
    "ncbi_link": "GAL4: 
lacZ: 
esg: 34903
Las: 40259"
  },
  {
    "caption": "K-M. Representative images of midgut  sections from the R4 region of Drosophila carrying esgts-GAL4-driven expression of lacZ  cDNA (K, control), Las RNAi (L), or Las RNAi and dominant negative form of EGFR (EGFR-DN, M). GFP (green) and Dl staining  (red) was used to visualize ISCs. Data information: DAPI stained nuclei are shown in blue. Scale bars represent 10 μm",
    "ncbi_link": "lacZ: 
GAL4: 
EGFR: 37455
esg: 34903
Las: 40259"
  },
  {
    "caption": "A Histochemical stained roots  from composite plants transformed with proMtNPF6.5:GUS  (left column), proMtNPF6.7:GUS (middle column), proMtNPF6.6:GUS (right column).",
    "ncbi_link": "GUS: 
NPF6.5: 
NPF6.6: 
NPF6.7: "
  },
  {
    "caption": "B Expression of  MtNPFs in  roots after transfer to media containing different levels of NO3- for 30 minutes. C=KCl  control, N=KNO3 (Biological replicates: n = 3 (3 pooled root  organs in each replicate), asterisk denotes significance p<0.05, Student's t-test). The means of all samples were compared to that of their concentration-matched KCl controls. Expression is shown relative to  Ubiquitin.",
    "ncbi_link": "Ubiquitin: 11430063"
  },
  {
    "caption": "A, B  I-V responses in oocytes (subtracted of the water injected controls) exposed to 40 mM Cl  at  pH5.8 (A) and pH7.4 (B). The currents were measured while the oocyte plasma membrane  was clamped at -60 mv to between 20 and -140 mv for 120 ms with -20 mv increments for each Cl- concentration. The Cl- -elicited current values in D were obtained by subtracting the currents in water  injected  oocytes from the MtNPF6.5  injected  oocytes at each Cl- concentration Data information: Value = mean ± SEM, biological replicates: n = 4",
    "ncbi_link": "NPF6.5: "
  },
  {
    "caption": "C, D  I-V responses in the (C)  water and (D) MtNPF6.5 (subtracted of the water injected controls) injected oocytes exposed to different concentrations of Cl- at pH5.8. The currents were measured while the  oocyte plasma membrane  was clamped at -60 mv to between 20 and -140 mv for 120 ms with -20 mv increments for each Cl-  concentration. The  Cl-  -elicited current values in D were obtained by subtracting the currents in water  injected oocytes  from the MtNPF6.5 injected oocytes  at each Cl-  concentration. Data information: Value = mean ± SEM, biological replicates: n = 6",
    "ncbi_link": "NPF6.5: "
  },
  {
    "caption": "C  Oocytes were exposed to 1.17 mM 36Cl- for 2h with 1 and 10 mM NO3-. Biological replicates: n=6 (4  oocytes in each sample). D The same data as in C is shown without AtNPF6.3 to allow for better comparison between MtNPFs. Biological replicates: n=6 (4 oocytes in each sample). Data information: Asterisks denote significant difference: **P<0.01, *P<0.05 (Student's t-test). In the boxplots, horizontal black bars represent the median, and black cross represent the mean. Boxes represent the middle 50% of the distribution, and whiskers represent the entire spread of the data. Means were compared using Student's t-test, α= 0.05.",
    "ncbi_link": "NPF6.3: 837763"
  },
  {
    "caption": "E Relative MtNPF expression following treatment with 5mM  KNO3 +100mM NaCl Data information: expression shown is relative to Ubiquitin; *p< 0.05, Student's t-test; biological replicates: n= 3 (3 pooled root organs in each replicate) ±SEM.",
    "ncbi_link": "Ubiquitin: 11430063"
  },
  {
    "caption": "A The induction of  MtNPF6.7 and repression of  MtNPF6.5 by  NO3- requires MtNLP1. Plants were grown on FP  plates and then treated with 5 mM KNO3. expression shown is relative to UBQ; *p<0.05, Student's t-test; biological replicates: n= 3 (3 pooled  root organs in each replicate).",
    "ncbi_link": "NLP1: 
NPF6.5: 
NPF6.7: 
UBQ: 11430063"
  },
  {
    "caption": "B The switch from Cl-  to NO3-  as the major anion upon NO3- addition is lost in mtnlp1. Plants were grown on FP plates and then treated with 5 mM KNO3 treatment. *p< 0.05, Student's t-test; biological replicates: n=4 (3 pooled root organs in each replicate).C",
    "ncbi_link": "nlp1: "
  },
  {
    "caption": "(a) Effect of steroids on MERS-CoV replication. Vero cells were infected with MERS-CoV at MOI = 0.01 in the presence of steroids for 24 h. The viral titer in the cell supernatant was quantified by standard plaque assay using Vero/TMPRSS2 cells. Cell viability in the presence of steroids was quantified by WST assay at 24 hours post-infection (hpi).",
    "ncbi_link": "TMPRSS2: "
  },
  {
    "caption": "(a) Intracellular SARS-CoV-2 RNA (6 hpi). VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 at MOI = 1 in the presence of 10□μM compounds for 6 h. Cellular viral RNA was quantified by real-time PCR using the E gene primer/probe set.",
    "ncbi_link": "TMPRSS2: 
E: 43740570"
  },
  {
    "caption": "(b) Culture Medium SARS-CoV-2 RNA (27 hpi). VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 at MOI = 0.01 in the presence of ciclesonide for 27 h. Viral RNA in culture medium was quantified by real-time PCR using the E gene primer/probe set. Cell viability in the presence of ciclesonide was quantified at 27 hpi by WST assay.",
    "ncbi_link": "TMPRSS2: 
E: 43740570"
  },
  {
    "caption": "(A) Expression of all rate-limiting glycolytic isoenzymes in R1 cells after knockdown of Stat3 using three independent shRNAs compared to an empty vector control shRNA (sh-ctrl), as measured by Western blot. β-actin was employed as a loading control throughout. (B-I) Expression of the pluripotency genes c-Myc, Oct-4, Nanog, Klf4 and Sox-2 in R1 cells after knockdown of Hk2 (B), Pfkl (C), Hk1 (D), Hk3 (E), Pfkm (F), Pkm2 (G), Pklr (H) and Pfkp (I) glycolytic enzymes using two or three independent shRNAs, as measured by Western blot. D",
    "ncbi_link": "Hk1: 15275
Hk2: 15277
Hk3: 212032
Pfkl: 18641
Pfkm: 18642
Pfkp: 56421
Pklr: 18770
Pkm2: 18746
Stat3: 20848"
  },
  {
    "caption": "(A-C) Expression of Pfkp mRNA levels (top panels) and Stat3 and Pfkp protein expression (bottom panels) after knockdown of Stat3 using three independent shRNAs in either R1 cells (A) or E14 cells (B) or after overexpression of Stat3 in R1 cells (C), as measured by qPCR and Western blot, respectively. β-actin was employed as a loading control throughout.",
    "ncbi_link": "Pfkp: 56421
Stat3: 20848"
  },
  {
    "caption": "ChIP assays against Stat3 p-Stat3 (Y705) or isotype-matched immunoglobulin G (IgG) (F), as measured by PCR, and images were representative of three independent experiments. Nanog promoter is shown as a positive control.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "(G) Transcriptional activity of the indicated pGL3-based Pfkp promoter or mutant constructs expressed in HEK293T cells with or without overexpression of Stat3, as measured by luciferase reporter assay (top panel). Western blotting was used to verify Stat3 expression (bottom panel).",
    "ncbi_link": "Pfkp: 56421
Stat3: 20848"
  },
  {
    "caption": "(B) Representative images of alkaline phosphatase-stained colonies formed by R1 cells after overexpression of Pfkp. Images were representative of three independent experiments.",
    "ncbi_link": "Pfkp: 56421"
  },
  {
    "caption": "(K, L) Representative images of immunofluorescence staining in control and Pfkp knockdown R1 cells for Sox17 following definitive endoderm differentiation (K) or Foxa2 following definitive endoderm differentiation (L). Green staining indicates positive cells with nuclei counterstained with DAPI. Images were representative of three independent experiments. (M, N) Quantitative analysis of Sox17 (M) and Foxa2 (N) in R1 cells from (K) and (L), respectively as determined by flow cytometry. Representative profiles (left panels) and quantitation (right panels) as a percentage of total cells.",
    "ncbi_link": "Pfkp: 56421"
  },
  {
    "caption": "(E-F) Co-IP assays mapping interactions between Pfkp and fragments of Lin41 (E), interactions between Lin41 and fragments of Pfkp (F) in HEK293T cells.",
    "ncbi_link": "Pfkp: 56421
Lin41: 636931"
  },
  {
    "caption": "(J, K) Expression of Lin41 in control versus Pfkp knockdown R1 cells without or with MG132 treatment (J) or with Lactacyctin treatment (K), as determined by Western blot.",
    "ncbi_link": "Pfkp: 56421"
  },
  {
    "caption": "(F) HEK293T cells were co-transfected with the indicated vectors to overexpress Pfkp in combination with HA-ubiquitin (Ub) and the individual wildtype Flag-Lin41 or serine substitution mutants. Lin41 ubiquitination levels were determined using Western blotting against HA (top panels) with input samples analyzed in parallel to verify transfection efficiency (bottom panels).",
    "ncbi_link": "Flag: 
HA: 
Ub: 
ubiquitin: 
Pfkp: 56421
Lin41: 636931"
  },
  {
    "caption": "(G) Control or Pfkp knockdown R1 cells were co-transfected with the individual wildtype Flag-Lin41 or serine substitution mutants and Lin41 ubiquitination levels determined as per (F) using Western blotting against Flag. (H) In vitro ubiquitination assays employing the products from in vitro kinase assays employing recombinant GST-Lin41 and Flag-Pfkp, with Lin41 ubiquitination measured by Western blotting against Lin41. (",
    "ncbi_link": "Flag: 
Pfkp: 56421
Lin41: 636931"
  },
  {
    "caption": "(G-J) RNA pull-down assays measuring interactions between Fgf5 (G), Otx2 (H), Sox1 (I), and Pax2 (J) mRNAs and endogenous Lin41 in R1 cells. Recovery of each mRNA was compared in sense and anti-sense probes using qPCR (top) with Western blotting used to detect Lin41(bottom).",
    "ncbi_link": "Fgf5: 14176
Otx2: 18424
Pax2: 18504
Sox1: 20664"
  },
  {
    "caption": "(K) Relative stability of mRNAs for the ectodermal genes Fgf5, Otx2, Sox1, and Pax2 R1 cells in control and Pfkp knockdown EBs at Day 6, as determined in actinomycin D chase assays. (L) Relative stability of ectodermal gene mRNAs measured as per (K) in Day 6 Pfkp knockdown EBs transfected with or without Lin41.",
    "ncbi_link": "Fgf5: 14176
Otx2: 18424
Pax2: 18504
Pfkp: 56421
Sox1: 20664
Lin41: 636931"
  },
  {
    "caption": "The mRNA expression of splicing regulator SRSF2 and splicing factor PCBP2 during hematopoietic differentiation were measured by RT-qPCR. The ACTB gene was used as a control. Results given are mean ± standard deviation (SD). P-values were determined by an unpaired two-tailed Student's t-test. n ≥ 3 biological replicates.",
    "ncbi_link": "ACTB: 60
PCBP2: 5094
SRSF2: 6427"
  },
  {
    "caption": "The representative FACS plots show the frequency of CD31+CD34+ EPCs in the GFP+ population at day 5 with 1.25 nM PLB supplementation alone or in combination with NUMB_S ectopic expression from day 2.5. The bar graph denotes the percentage of CD31+CD34+ in GFP+ cells as described in (F). P-values were determined by an unpaired two-tailed Student's t-test.",
    "ncbi_link": "NUMB_S: 8650"
  },
  {
    "caption": "On day 5 of hematopoietic differentiation, the inclusion or exclusion of NUMB exon 9 were detected by RT-PCR with 1.25 nM PLB supplementation or SRSF2 exogenous expression alone or their combinational treatment from day 2.5. The bar graph showing the signaling intensity of each specific band from the RT-PCR electropherogram.",
    "ncbi_link": "NUMB: 8650
SRSF2: 6427"
  },
  {
    "caption": "The top panel depicts the location of specific primers targeting NUMB_S and NUMB_L isoform. The bottom bar graph showing the expression of NUMB_S and NUMB_L in cells on day 5 of differentiation with 1.25 nM PLB supplementation or SRSF2 exogenous expression alone or their combinational treatment from day 2.5 with RT-qPCR.",
    "ncbi_link": "NUMB_L: 8650
NUMB_S: 8650
SRSF2: 6427"
  },
  {
    "caption": "The heatmap plotting the expression of NUMB_S and the key components in NOTCH signaling in day 2-APLNR+ cells, day 5-DMSO treated and day 5-PLB treated cells (2.5 nM), respectively. The NOTCH components were divided into groups of upregulated, downregulated, and unchanged by comparison between DMSO and PLB treated cells. The heatmap was scaled with Z-Score using the log2(FPKM) expression of indicated genes. n=2 technical replicates",
    "ncbi_link": "NUMB_S: 8650"
  },
  {
    "caption": "The representative FACS plots indicating the generation of CD31+CD34+ EPCs on day 5 of differentiation with or without HES1 overexpression. DOX was treated from day 2.5 to 5 to induce HES1 overexpression. Statistical analysis of the percentage of CD31+CD34+ EPCs of (H).",
    "ncbi_link": "HES1: 3280"
  },
  {
    "caption": "The percentage of dead cells was determined at the indicated timepoints by trypan blue exclusion assay (mean ± s.d.; n = 3). (a) Bif-1+/+ (wild type; WT) and Bif-1−/− (knockout; KO) MEFs were cultured in EBSS for 0, 3, 6 or 12 h. (b) Bif-1−/− MEFs stably transfected with a Bif-1 expression plasmid or control empty vector were incubated in EBSS for 0 or 12 h. Recovery of Bif-1 expression in Bif-1−/− cells was determined by immunoblot analysis (inset).",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(c) Bif-1+/+ and Bif-1−/− MEFs were cultured in EBSS in the presence of 50 μM z-VAD-fmk or control DMSO for 0, 3, 6 or 12 h.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(d) Bax+/+Bak+/+ (WT) and Bax−/−Bak−/− (DKO) MEFs were cultured in EBSS in the presence of 50 μM z-VAD-fmk or control DMSO for 0, 6 or 12 h.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(a, b) Bif-1+/+ and Bif-1−/− MEFs or Bax+/+Bak+/+ and Bax−/−Bak−/− MEFs were infected with Beclin 1 shRNA or control shRNA (SCR shRNA) lentiviruses. Twenty-four hours after infection, the medium was replaced with fresh culture medium and the cells were allowed to recover for an additional 48 h. The cells were then cultured in EBSS for 0, 6 or 12 h, and the percentage of dead cells was determined by trypan blue exclusion assay (mean ± s.d.; n = 3). Knockdown of Beclin 1 expression was confirmed by immunoblot analysis (insets).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Beclin 1: 56208
Bif-1: 54673"
  },
  {
    "caption": "(c, d) Bif-1+/+ and Bif-1−/− MEFs were pre-treated with 10 mM 3-methyladenine (3-MA), 0.2 μM wortmannin (WM) or control DMSO for 30 min followed by culture in EBSS for the indicated times. The percentage of dead cells was determined by trypan blue exclusion assay (mean ± s.d.; n = 3).",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(c, d) Bif-1+/+ and Bif-1−/− MEFs were pre-treated with 10 mM 3-methyladenine (3-MA), 0.2 μM wortmannin (WM) or control DMSO for 30 min followed by culture in EBSS for the indicated times. The percentage of dead cells was determined by trypan blue exclusion assay (mean ± s.d.; n = 3). Immunoblot analyses were performed to detect LC3 modification and caspase-3 activation.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(e) Atg5+/+ and Atg5−/− MEFs were cultured in EBSS in the presence of 50 μM of z-VAD-fmk or control DMSO for 0, 6 or 12 h. The percentage of dead cells was determined by trypan blue exclusion assay (mean ± s.d.; n = 3).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) Total cell lysates (TCL) were prepared from Atg5+/+ and Atg5−/− MEFs cultured in EBSS for the indicated times and subjected to immunoblot analyses. Uncropped images of the immunoblots in a, b, d and f are shown in the Supplementary Information, Fig. S5.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Bif-1+/+ and Bif-1−/− MEFs were cultured in complete medium (CM) or EBSS for 3 h and analysed by transmission electron microscopy. Arrows indicate autophagosomes. The number of autophagosomes per cross-sectioned cell was counted (mean ± s.d.; n = 42).",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(b) Bif-1+/+ and Bif-1−/− MEFs were transfected with GFP-LC3, cultured in LC3 or complete medium for 3 h, then analysed by fluorescent microscopy. The number of GFP-LC3 dots per GFP-positive cell was counted (mean ± s.d.; n = 35).",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(c) Bif-1+/+ and Bif-1−/− MEFs were cultured in EBSS for the indicated times and subjected to immunoblot analysis with anti-LC3, anti-α-tubulin and anti-β-actin antibodies.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(d) Bif-1−/− MEFs stably transfected with a Bif-1 expression plasmid or control empty vector were cultured in EBSS for 0, 3 or 6 h and subjected to immunoblot analysis. The immunoblotting results of LC3 in c and d were quantified as the percentage of LC3-II out of total LC3 (LC3-I + LC3-II) and are represented in bar graphs.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(e) Stable Bif-1 shRNA-expressing clones or control HeLa cells transfected with GFP-LC3 were cultured in complete medium or EBSS for 2 h and analysed by fluorescent microscopy. The number of GFP-LC3 dots per GFP-positive cell was quantified (mean ± s.d.; n = 66).",
    "ncbi_link": "Bif-1: 51100"
  },
  {
    "caption": "(f) Bif-1 knockdown HeLa cells were transfected with GFP-LC3 in combination with Bif-1 shRNA-resistant Bif-1-HcRed, Bif-1ΔBAR-HcRed or empty HcRed vector for 20 h. The cells were then cultured in EBSS or complete medium for 2 h and the number of GFP-LC3 dots per HcRed-positive cell was determined using a fluorescence microscope (mean ± s.d.; n = 35).",
    "ncbi_link": "Bif-1: 51100"
  },
  {
    "caption": "(a) COS7 cells were transfected with Bif-1-HcRed together with GFP-Atg5 or GFP-LC3. Twenty hours after transfection, the cells were cultured in EBSS (middle and bottom panels) or complete medium (top panel) for 2 h and subjected to confocal microscopy analysis. Magnified images are shown as insets. Representative Bif-1-Atg5 or Bif-1-LC-3 double-positive foci are indicated by arrows.",
    "ncbi_link": "Atg5: 9474
LC3: 440738///81631///84557
Bif-1: 51100"
  },
  {
    "caption": "(a) Bif-1+/+ and Bif-1−/− MEFs were cultured in EBSS for 0 or 6 h and subjected to immunoprecipitation with anti-Bif-1 monoclonal antibodies. The resulting immune complexes and TCL were analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(d) 293T cells were transfected with GFP siRNA or UVRAG siRNA for 24 h, starved in 2 h for 2 h and subjected to immunoprecipitation with anti-Bif-1 monoclonal antibodies. The resulting immune complexes and TCL were analysed by immunoblotting with anti-Bif-1 and Beclin 1 polyclonal antibodies. The reduction of UVRAG protein expression by UVRAG siRNA was confirmed by immunoprecipitation and immunoblot analysis with anti-UVRAG polyclonal antibody. Uncropped images of the immunoblots are shown in the Supplementary Information, Fig. S5.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) HeLa cells were transfected with 0.2 μg GFP-LC3 and 0, 0.2 or 0.6 μg of Bif-1SH3-Myc expression plasmids for 24 h. The total amount of plasmid DNA was adjusted at 0.8 μg per transfection with the pcDNA3 vector. The cells were then cultured in EBSS or complete medium for 3 h and the number of GFP-LC3 dots per GFP-positive cell was determined using a fluorescence microscope (mean ± s.d.; n = 40).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(b) HeLa cells were transfected with GFP-LC3 in combination with either Bif-1SH3-HcRed, Endophilin A1SH3-HcRed or empty HcRed vector for 20 h. The cells were then cultured in 2 h or complete medium for 2 h and the number of GFP-LC3 dots per HcRed-positive cell was counted using a fluorescence microscope (mean ± s.d.; n = 46). Statistical significance in a and b was determined by Student's t-test and the asterisks indicate P 0.0001.",
    "ncbi_link": "LC3: 440738///81631///84557
Endophilin A1: 6456
Bif: 51100"
  },
  {
    "caption": "(a) Bif-1+/+ and Bif-1−/− MEFs were transfected with Flag-PI(3)KC3, then incubated in complete medium or EBSS for 2 h and subjected to an in vitro PI(3)KC3 kinase assay. The expression of Flag-PI(3)KC3 was confirmed by immunoblot analysis (left panel). A representative autoradiograph is shown (middle). The results were quantified by phosphoimaging with a Typhoon scanner and shown as fold activation (right). The data are presented as means ± s.d. of five independent experiments.",
    "ncbi_link": "Bif: 54673"
  },
  {
    "caption": "(b) Bif-1+/+ and Bif-1−/− MEFs were transfected with p40(phox) PX-EGFP, cultured in complete medium or EBSS for 2 h and analysed using a fluorescence microscope. The number of p40(phox) PX-EGFP-positive vesicles per cell was counted (mean ± s.d.; n = 35). Statistical significance in a and b was determined by Student's t-test.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(c) Stable Bif-1 shRNA clones or control HeLa cells were transfected with Flag-PI(3)KC3 alone or in combination with Flag-tagged Beclin 1 and UVRAG for 48 h and subjected to an in vitro PI(3)KC3 lipid kinase assay. The results were quantified and are shown as relative activities (mean ± s.d.; n = 3).",
    "ncbi_link": "Beclin 1: 8678
Bif-1: 51100
UVRAG: 7405"
  },
  {
    "caption": "(d) 293T cells were cotransfected with Flag-PI(3)KC3 and either wild-type Bif-1, Bif-1ΔSH3 or control empty vector for 24 h and subjected to an in vitro PI(3)KC3 kinase assay (mean ± s.d.; n = 3).",
    "ncbi_link": "Bif-1: 51100"
  },
  {
    "caption": "(a) Bif-1−/− mice exhibit moderate splenomegaly. The weight of spleens extirpated from Bif-1+/+ (n = 27) and Bif-1−/− (n = 34) mice (6-18-month old) was measured. Statistical significance was determined by Wilcoxon rank test.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(b) Hematoxylin and eosin staining of tumour tissues. Tumours were observed in 3 of 21 (14.3%) and 26 of 29 (89.7%) autopsied Bif-1+/+ and Bif-1−/− mice, respectively. The scale bars represent 50 μm.",
    "ncbi_link": "Bif-1: 54673"
  },
  {
    "caption": "(c) The CaaX motif of FBXL2 is required to bind p85α and p85β. HEK293T cells were transfected with either an empty vector (EV) or the indicated FLAG-tagged F-box proteins. The experiment was performed as described in a.",
    "ncbi_link": "CaaX: 25827
FBXL2: 25827"
  },
  {
    "caption": "(b) HeLa cells stably expressing FLAG-HA-tagged FBXL2 were transfected with either siRNAs targeting FBXL2 (four different siRNAs) or a non-silencing siRNA (NS). Cells were lysed, and proteins were immunoblotted as indicated. NT, non-transfected.",
    "ncbi_link": "FBXL2: 25827"
  },
  {
    "caption": "(c) During a 72-h serum starvation, NHFs were transfected with either an siRNA targeting FBXL2 (no. 1) or a non-silencing siRNA (NS). Cells were subsequently stimulated with media containing serum and collected at the indicated time points for immunoblotting. The graph shows FBXL2 mRNA levels in the different samples analysed using real-time PCR in triplicate measurements. The values represent the ratios between FBXL2 and GAPDH mRNAs. SR, serum re-addition.",
    "ncbi_link": "GAPDH: 
FBXL2: 25827"
  },
  {
    "caption": "(d) HEK293T cells were transfected with HA-tagged p85β, FLAG-tagged FBXL2, FLAG-tagged FBXL2(ΔF-box) or an empty vector (EV) as indicated. After immunopurification with anti-FLAG resin, in vitro ubiquitylation of p85β was performed in the presence of E1, E2s and ubiquitin (Ub). Where indicated, an excess of methylated ubiquitin (MeUb) was also added. Samples were analysed by immunoblotting with the indicated antibodies. The ladder of bands with a relative molecular mass of >85,000 (lane 3) corresponds to ubiquitylated p85β. Immunoblots of whole-cell lysates (WCL) are shown at the bottom. Uncropped images of blots are shown in Supplementary Fig. S8",
    "ncbi_link": "FBXL2: 25827"
  },
  {
    "caption": "(c) p85β(ΔSH2C) is more stable than wild-type p85β. RPE1-hTERT cells were infected with either a retrovirus expressing wild-type p85β or p85β (ΔSH2C). Cells were incubated with cycloheximide (CHX) for the indicated times, collected and analysed by immunoblotting as indicated. In the graph, the amount of p85β (wild-type or mutant) is represented relative to the amount at time 0. (",
    "ncbi_link": "p85β: 5296"
  },
  {
    "caption": "(d) p85β (QR/AA) is more stable than wild-type p85β. HEK293T cells were infected with either a retrovirus expressing wild-type p85β or p85β (QR/AA). Cells were incubated with cycloheximide (CHX) for the indicated times, collected and analysed by immunoblotting as indicated. In the graph, the amount of p85β (wild-type or mutant) is represented relative to the amount at time 0.",
    "ncbi_link": "p85β: 5296"
  },
  {
    "caption": "(e) p85β (Y655A) is less stable than wild-type p85β. The experiment was performed as described in c except that p85β(Y655A) was used. In the graph, the amount of p85β (wild-type or mutant) is represented relative to the amount at time 0. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "p85β: 5296"
  },
  {
    "caption": "(a) The CaaX motif of FBXL2 is not required to bind PTPL1. HEK293T cells were transfected with either FLAG-tagged wild-type FBXL2 or FLAG-tagged FBXL2(CaaX/SaaX). 24 h post-transfection, cells were collected and whole-cell lysates (WCL) were immunoprecipitated (IP) and immunoblotted as indicated.",
    "ncbi_link": "FBXL2: 25827"
  },
  {
    "caption": "(c) PTPL1 stimulates the binding of FBXL2 to wild-type p85β, but not p85β(Y655A). HEK293T cells were transfected with GFP-tagged FBXL2 and either FLAG-tagged p85β or FLAG-tagged p85β(Y655A). Where indicated, HA-tagged PTPL1 or HA-tagged PTPL1(C/S) were also transfected. The experiment was performed as described in a.",
    "ncbi_link": "p85β: 5296
PTPL1: 5783"
  },
  {
    "caption": "(d) PTPL1 silencing inhibits the FBXL2-p85β interaction. HeLa cells stably expressing FLAG-tagged FBXL2 were transfected with either an siRNA targeting PTPL1 or a non-silencing siRNA (NS). Forty-eight hours post-transfection, cells were collected and whole-cell lysates (WCL) were immunoprecipitated (IP) and immunoblotted as indicated.",
    "ncbi_link": "PTPL1: 5783"
  },
  {
    "caption": "(e) During a 72-h serum starvation, NHFs were transfected twice with either siRNAs targeting FBXL2 or PTPL1, or a non-silencing siRNA (NS). Cells were subsequently re-stimulated with media containing serum and collected at the indicated time points for immunoblotting. SR, serum re-addition.",
    "ncbi_link": "FBXL2: 25827
PTPL1: Q12923///5783"
  },
  {
    "caption": "(f) HEK293T cells were transfected twice with either siRNAs targeting FBXL2 or PTPL1, or a non-silencing siRNA (NS). Cells were transfected with p85β(Y655A) and 16 h after cells were incubated with cycloheximide (CHX) for the indicated times, collected and analysed by immunoblotting as indicated.",
    "ncbi_link": "FBXL2: 25827
p85β: 5296
PTPL1: 5783"
  },
  {
    "caption": "g) During a 48-h serum starvation, U2OS cells stably transfected with a doxycycline-inducible p85β construct were transfected twice with either an siRNA targeting PTPL1 or a non-silencing siRNA (NS). During the last 16 h before collection, p85β expression was stimulated with doxycycline. Cells were subsequently re-stimulated with media containing serum and collected 30 min later. Denatured cell lysates were immunoprecipitated with an anti-FLAG resin and immunoblotted as indicated. The asterisk indicates a non-specific band. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "p85β: 5296
PTPL1: 5783"
  },
  {
    "caption": "a) During a 72-h serum starvation, NHFs were transfected with either siRNAs targeting FBXL2, p85β, both FBXL2 and p85β, or a non-silencing siRNA (NS). Cells were subsequently stimulated with media containing serum and collected at the indicated time points for immunoblotting. The graph at the right shows FBXL2 mRNA levels in the different samples analysed using real-time PCR in triplicate measurements. The values represent the ratios between FBXL2 and GAPDH mRNAs. SR, serum re-addition.",
    "ncbi_link": "GAPDH: 
FBXL2: 25827
p85β: 5296"
  },
  {
    "caption": "(a) During a 72-h serum starvation, NHFs were transfected with either siRNAs targeting FBXL2 (no. 1 or 2) or a non-silencing siRNA (NS). Cells were subsequently stimulated with media containing serum and collected at the indicated time points for immunoblotting. SR, serum re-addition.",
    "ncbi_link": "FBXL2: 25827"
  },
  {
    "caption": "(b) During a 72-h serum starvation, NHFs were transfected with either siRNAs targeting FBXL2, both FBXL2 and p85β, or a non-silencing siRNA (NS). Cells were subsequently stimulated with media containing serum and collected at the indicated time points for immunoblotting. SR, serum re-addition.",
    "ncbi_link": "FBXL2: 25827
p85β: 5296"
  },
  {
    "caption": "(c) U2OS cells stably transfected with a doxycycline-inducible p85β construct were serum starved for 48 h. During the last 16 h before collection, p85β expression was stimulated with doxycycline. Cells were subsequently stimulated with media containing serum and collected at the indicated time points for immunoblotting. SR, serum re-addition.",
    "ncbi_link": "p85β: "
  },
  {
    "caption": "F. BAZ2A read coverage quantification at ±1Kb from peak summit of BAZ2A-bound regions identified in PC3 cells and the corresponding reads for BAZ2A-BRD mutant (Y1775F) in PC3 cells. Statistical significance (P-values) was calculated using two-tailed t-test (***< 0.001). Data information: Boxplots show the median and quartiles with the whiskers extending to the most extreme data point within 1.5 times the interquartile range.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "G. Regions bound by  BAZ2A in  PC3  cells are enriched in  H3K14ac. Read coverage quantification for H3K14ac levels at regions bound by  BAZ2A   in PC3 cells (BAZ2Awt and BAZ2A-BRD mutant (Y1775F)) at ±1Kb from BAZ2A  peak summits. Statistical significance (P-values) was calculated using two-tailed t-test (***< 0.001). Data information: Boxplots show the median and quartiles with the whiskers extending to the most extreme data point within 1.5 times the interquartile range.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "F. qRT-PCR showing increased expression levels of genes with  BAZ2A-bound promoter and downregulated in metastatic tumors (AOX1, MANB2, DMPK, and DDB1 in PC3  cells treated with siRNA-EP300. Data were from three independent experiments. Values were normalized to GAPDH mRNA. Statistical significance (P-values) was calculated using two-tailed t-test (*<0.05, ****<0.0001). Error bars represent SD.",
    "ncbi_link": "AOX1: 316
DDB1: 1642
DMPK: 1760
EP300: 2033
GAPDH: 2597
MANB2: 4126"
  },
  {
    "caption": "H. qRT-PCR  showing increased expression levels of   BAZ2A-bound C2-enhancer genes in PC3 cells treated with siRNA-EP300. Data were from three independent experiments. Values were normalized to  GAPDH mRNA. Statistical significance (P-values) was calculated using two-tailed t-test (*<0.05, **<0.001). Error bars represent SD.",
    "ncbi_link": "EP300: 2033
GAPDH: 2597"
  },
  {
    "caption": "C.  qRT-PCR of genes differentially expressed in PC3-CSCs compared to PC3 cells showing the upregulation of CSC markers (ALDH1A2, LGR5, CD24) and downregulation of genes related to developmental processes (HOXA1, HOXA4, SOX7). Data are from two independent experiments. mRNA levels were normalized to GAPDH.",
    "ncbi_link": "ALDH1A2: 8854
CD24: 100133941
GAPDH: 2597
HOXA1: 3198
HOXA4: 3201
LGR5: 8549
SOX7: 83595"
  },
  {
    "caption": "D. BAZ2A is required for the dedifferentiation of PC3 into PC3-CSCs. Left panel: Representative images from two independent experiments showing the impairment of  PC3  cells to form tumorspheres  upon stable depletion of BAZ2A. Right panel: BAZ2A mRNA levels in three independent PC3  cell lines stably expressing shRNA-BAZ2A were measured by qRT-PCR and normalized to GAPDH  mRNA from 2 independent experiments.",
    "ncbi_link": "BAZ2A: 11176
GAPDH: 2597"
  },
  {
    "caption": "E. Left panel: qRT-PCR showing BAZ2A mRNA levels in PC3  cells depleted of endogenous BAZ2A with siRNA specifically targeting human BAZ2A sequences and expressing mouse BAZ2Awt and BAZ2A-BRD mutant (BAZ2AY1775F). Values were normalized to MRPS7  mRNA. Data are from 3 independent experiments. Right panel: Quantification of  tumorspheres from 3 independent experiments. Statistical significance (P-values) was calculated using two-tailed t-test (* <0.05; **< 0.01). Error bars represent SD.",
    "ncbi_link": "BAZ2A: 11176
BAZ2A: 116848
MRPS7: 51081"
  },
  {
    "caption": "B. Cell proliferation curves of PC3 cells treated with siRNA-BAZ2A. Error bars represent the standard deviation from three independent experiments. C. Cell proliferation curves of PC3  cells treated with 5μM BAZ2-ICR  and  GSK2801. Error bars represent the standard deviation from three independent experiments. ",
    "ncbi_link": "BAZ2A: 11176"
  },
  {
    "caption": "A. Representative  bright field images  of organoids derived from mouse prostate cells treated with DMSO, BAZ2-ICR  (5μM), GSK2801 (5μM) or GSK126 (5μM) inhibitors followed by transduction with shRNA-Control or shRNA-Pten.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "C. Representative images of Ki67-immunostained mouse prostate organoid sections expressing shRNA-control and shRNA-Pten and treated with DMSO or BAZ2-ICR (5μM). D. Quantification of  Ki67+ cells in mouse prostate organoids  shown in C. **< 0.01, ****P < 0.0001, two-tailed Student's t test; ns, not significant. The median values are represented by a line. ",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "E. Quantification of  mouse prostate organoids  per field expressing shRNA-control and shRNA-Pten and treated with DMSO, GSK126  (5μM), BAZ2-ICR (5μM), or GSK2801  (5μM). Values were normalized to shRNA-control samples. Average values of two independent experiments.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(E). Relative luciferase activity  of the sensor (+) reporter or sensor (-) reporter induced by expression vectors of the top 5 genes identified in the screen or the GFP vector in HEK293-FT  cells. Error bars show SD; n=3. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(F). Heat map of relative miRNA  expression of various miRNAs in HEK-293FT cells transfected with expression vectors of the top 5 genes from the screen, or the ctrl (GFP) vector. Red color represents suppressed expression compared with ctrl (GFP). n=3.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A). Volcano plot of TaqMan array  showing the mean average expression and p-value of miRNA expression profiles between TruB1 KD and ctrl (scramble). N=3. Significance was assessed using 2‐tailed Student's t‐test. MiRNAs suppressed (Relative expression TruB1 KD / ctrl <0.8 and p-value < 0.1) are enclosed by the red square.",
    "ncbi_link": "TruB1: 142940"
  },
  {
    "caption": "(D). Relative expression  of let-7 family miRNAs and other miRNAs in HEK293FT  cells with TruB1 KD or ctrl (siRNA) determined by qRT-PCR. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show SD.",
    "ncbi_link": "TruB1: 142940"
  },
  {
    "caption": "(C). Relative miRNA expression of  let-7a in HEK-293 cells infected with tetracycline-inducible expressing lentiviruses for TruB1, mt1, mt2 or GFP 5 days after doxycycline treatment, as determined by qRT-PCR. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show SD.",
    "ncbi_link": "GFP: 
let-7a: 406881///406883///406882
TruB1: 142940"
  },
  {
    "caption": "(D). Northern blotting for  let-7a and RNU6B in HeLa cells infected with lentiviruses  encoding tetracycline-inducible expression of TruB1, mt1, mt2, or GFP, 5 days after doxycycline treatment.",
    "ncbi_link": "GFP: 
RNU6B: 
let-7a: 406882///406883///406881
TruB1: 142940"
  },
  {
    "caption": "(G). Location of pseudouridine  sites detected by the  CMC primer extension method. Total RNA purified from HEK-293FT  cells were treated with CMC. CMC treated RNA  were reverse-transcribed   with RI-labelled specific primers for tRNAphe or  pri-let-7b. ddATP was used for sequence control. Pseudouridines are indicated by black arrows.",
    "ncbi_link": "pri-let-7b: 406884"
  },
  {
    "caption": "(A).  RIP analysis of pri-let-7a1 and Flag-TruB1   from HEK-293FT cells. RNA was extracted from  IP material and analyzed by  qRT-PCR. HEK-293FT cells were infected with lentiviruses encoding  tetracycline-inducible expression of TruB1, mt1, mt2, or GFP and treated with doxycycline. Error bars show SD; n=3. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*.",
    "ncbi_link": "GFP: 
pri-let-7a1: 406881
TruB1: 142940"
  },
  {
    "caption": "(B). EMSA of 32p-ATP-labelled pri-let-7a1  or  pri-let-7a1 loop mt mixed with recombinant TruB1, mt1 or mt2 at several doses. RNP: Ribonucleoprotein complexes.",
    "ncbi_link": "pri-let-7a1: 406881"
  },
  {
    "caption": "(A). In vitro processing assay for RI-labelled pri-let-7a1. Autoradiographs of gels showing  pri-let-7a1 treated with whole cell lysate (WCL) from HEK-293FT cells transfected with GFP, TruB1, mt1, or mt2 (overexpression, left), and TruB1 KD or ctrl (siRNA, right). Dicer  KD was used to show the height of pre-let-7a1. (B) RI  intensities of (A) were quantified and normalized to ctrl. Relative processing rate of pri-let-7a1 into pre- and mature- are shown. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show SD.",
    "ncbi_link": "GFP: 
Dicer: 23405
pre-let-7a1: 406881
pri-let-7a1: 406881
TruB1: 142940"
  },
  {
    "caption": "(C). RIP  assay of pri-let-7a1 and DGCR8  from HEK-293FT cells. Western blotting for input or immunoprecipitate (IP) using anti-DGCR8 antibody and anti-actin antibody are shown on top. RNA was extracted from  IP  material and analyzed by qRT-PCR (bottom). Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. (D).  RIP assay of pri-let-7a1  and Flag-tagged TruB1  from HEK-293FT  cells with  Lin28B KD or ctrl (siRNA). Western blotting for input or  IP material using anti-Flag antibody, anti-Lin28B antibody, and anti-actin  antibody are shown on top. RNA was extracted from IP  material and analyzed by qRT-PCR (bottom). Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show",
    "ncbi_link": "Lin28B: 389421
pri-let-7a1: 406881"
  },
  {
    "caption": "(B). Relative luciferase activity of KRAS reporter or Ctrl (empty) reporter in HEK293FT cells infected with lentiviruses expressing tetracycline-inducible TruB1, mt1, mt2, or GFP 5 days after doxycycline treatment. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show SD.",
    "ncbi_link": "GFP: 
KRAS: 3845
TruB1: 142940"
  },
  {
    "caption": "(D). Relative expression of let-7 families determined by  qRT-PCR in HEK-293FT cells with KD of let-7  family members or ctrl (using 2'-O-methylated antisense inhibitor). Significance was assessed using 2‐tailed Student's t‐test, < 0.05*. Data information: All experiments were performed in triplicate. Error bars show SD.",
    "ncbi_link": "let-7: 406885///406886///406887///406888///406889///406881///406890///406883///406891///406882///406884"
  },
  {
    "caption": "(E). Real-time glo assay for HEK293FT cells infected with lentiviruses expressing  tetracycline-inducible TruB1  or GFP, 5 days after doxycycline treatment, with or without KD of  let-7 family members. GFP: GFP  without  let-7 KD. WT: overexpression of wild type TruB1 without  let-7 KD. WT + let7 KD: WT: overexpression of wild type TruB1  with let-7 KD. GFP  + let-7KD: GFP with let-7 KD. Significance was assessed using 2‐tailed Student's t‐test, < 0.05*.",
    "ncbi_link": "GFP: 
let-7: 406881///406883///406882///406884///406885///406886///406887///406888///406889///406890///406891
let7: 406891///406890///406889///406888///406887///406886///406885///406884///406882///406883///406881
TruB1: 142940"
  },
  {
    "caption": "A. qPCR  analyses of GD9+6h male embryos  for: Pecam1  (Ctrl = 1.00 ± 0.17 N=8,  Poly I:C = 0.89 ± 0.23 N=13), CD248  (Ctrl = 1.00 ± 0.20 N=6, Poly I:C = 1.35 ± 0.31 N=11), Vegfa  (Ctrl = 1.00 ± 0.19 N=8, Poly I:C = 0.15 ± 0.04 N=8, Student's t test, ***p < .001), Pdfgb  (Ctrl = 1.00 ± 0.23 N=5, Poly I:C  = 1.10 ± 0.18 N=13), Tgfb1  (Ctrl = 1.00 ± 0.21 N=7, Poly I:C = 1.76 ± 0.22 N=10, Mann-Whitney U test, *p < .05), Tgfb2  (Ctrl = 1.00 ± 0.28 N=6,  Poly I:C = 1.37 ± 0.28 N=13), Tgfb3  (Ctrl = 1.00 ± 0.51 N=6, Poly I:C  = 0.73 ± 0.19 N=10), Foxf2  (Ctrl = 1.00 ± 0.45 N=8, Poly I:C = 0.46 ± 0.18 N=13) mRNAs. B. qPCR  analyses of E17 male cortices  for: Pecam1  (Ctrl = 1.00 ± 0.63 N=10, Poly I:C = 3.07 ± 1.58 N=8; Mann-Whitney U test, *p < .05), CD248  (Ctrl = 1.00 ± 0.23 N=10, Poly I:C = 3.33 ± 0.79 N=9; Mann-Whitney U test, **p < .01), Vegfa  (Ctrl = 1.00 ± 0.10 N=8,  Poly I:C  = 1.70 ± 0.29 N=5; Mann-Whitney U test, *p < .05), Pdfgb  (Ctrl = 1.00 ± 0.75 N=9,  Poly I:C = 2.05 ± 0.96 N=9; Mann-Whitney U test, *p < .05), Tgfb1  (Ctrl = 1.00 ± 0.16 N=7,  Poly I:C = 15.27 ± 5.75 N=7; Mann-Whitney U test, ***p < .001), Tgfb2  (Ctrl = 1.00 ± 0.16 N=8,  Poly I:C = 3.82 ± 1.05 N=6; Mann-Whitney U test, *p < .05), Tgfb3  (Ctrl = 1.00 ± 0.10 N=9, Poly I:C = 10.58 ± 6.73 N=8; Mann-Whitney U test, ***p < .001); Foxf2  (Ctrl = 1.00 ± 0.06 N=5,  Poly I:C = 2.60 ± 0.57 N=8; Mann-Whitney U test, *p < .05) mRNAs. C. qPCR  analyses of P90 male cortices  for: Pecam1  (Ctrl = 1.00 ± 0.18 N=8, Poly I:C = 0.85 ± 0.08 N=8), CD248  (Ctrl = 1.00 ± 0.20 N=9, Poly I:C = 0.93 ± 0.11 N=8), Vegfa  (Ctrl = 1.00 ± 0.07 N=8, Poly I:C  = 0.75 ± 0.06 N=8; Mann-Whitney U test, *p < .05); Pdfgb  (Ctrl = 1.00 ± 0.20 N=8, Poly I:C  = 1.11 ± 0.17 N=4), Tgfb1  (Ctrl = 1.00 ± 0.29 N=5, Poly I:C  = 2.37 ± 0.47 N=7; Mann-Whitney U test, *p < .05); Tgfb2  (Ctrl = 1.00 ± 0.29 N=4, Poly I:C = 1.19 ± 0.26 N=7), Tgfb3  (Ctrl = 1.00 ± 0.18 N=10, Poly I:C = 1.78 ± 0.50 N=11) mRNAs. D. qPCR  analyses of GD9+6h female embryos  for: Pecam1  (Ctrl = 1.00 ± 0.27 N=10, Poly I:C = 2.22 ± 0.50 N=6), CD248  (Ctrl = 1.00 ± 0.27 N=10, Poly I:C = 2.32 ± 0.57 N=6; Mann-Whitney U test, *p < .05), Vegfa  (Ctrl = 1.00 ± 0.38 N=8, Poly I:C = 0.29 ± 0.03 N=5; Mann-Whitney U test, *p < .05), Pdfgb  (Ctrl = 1.00 ± 0.36 N=10, Poly I:C = 1.31 ± 0.47 N=6), Tgfb1  (Ctrl = 1.00 ± 0.16 N=8, Poly I:C = 1.63 ± 0.42 N=7), Tgfb2  (Ctrl = 1.00 ± 0.33 N=9, Poly I:C = 1.75 ± 0.29 N=6; Mann-Whitney U test, *p < .05), Tgfb3  (Ctrl = 1.00 ± 0.29 N=9, Poly I:C = 1.33 ± 0.51 N=6), Foxf2  (Ctrl = 1.00 ± 0.28 N=9, Poly I:C = 1.71 ± 0.52 N=6) mRNAs. E. qPCR  analyses of E17 female cortices  for: Pecam1  (Ctrl = 1.00 ± 0.34 N=6, Poly I:C  = 0.27 ± 0.08 N=8), CD248  (Ctrl = 1.00 ± 0.27 N=8, Poly I:C = 1.04 ± 0.28 N=9), Vegfa  (Ctrl = 1.00 ± 0.70 N=5,  Poly I:C = 0.32 ± 0.13 N=5), Pdfgb  (Ctrl = 1.00 ± 0.38 N=6, Poly I:C = 0.19 ± 0.07 N=9), Tgfb1  (Ctrl = 1.00 ± 0.33 N=5, Poly I:C = 0.09 ± 0.03 N=6), Tgfb2  (Ctrl = 1.00 ± 0.32 N=7, Poly I:C = 0.45 ± 0.11 N=8), Tgfb3  (Ctrl = 1.00 ± 0.38 N=7,  Poly I:C = 0.40 ± 0.20 N=9), Foxf2  (Ctrl = 1.00 ± 0.18 N=5, Poly I:C = 1.04 ± 0.28 N=8) mRNAs. F. qPCR  analyses of P90 female cortices  for: Pecam1  (Ctrl = 1.00 ± 0.15 N=5, Poly I:C = 0.69 ± 0.15 N=5), CD248  (Ctrl = 1.00 ± 0.13 N=5, Poly I:C = 0.58 ± 0.09 N=5), Vegfa  (Ctrl = 1.00 ± 0.38 N=6, Poly I:C = 1.53 ± 0.38 N=8), Pdfgb  (Ctrl = 1.00 ± 0.16 N=9, Poly I:C = 1.77 ± 0.35 N=17), Tgfb1  (Ctrl = 1.00 ± 0.26 N=13, Poly I:C  = 1.30 ± 0.23 N=14), Tgfb2  (Ctrl = 1.00 ± 0.27 N=11,  Poly I:C = 0.59 ± 0.06 N=4), Tgfb3  (Ctrl = 1.00 ± 0.45 N=11, Poly I:C = 0.51 ± 0.06 N=4) mRNAs. G. qPCR  analyses of GD9+6h male embryos  for Il1α  (Ctrl = 1.00 ± 0.29 N=7, Poly I:C = 2.10 ± 0.57 N=17), Il1β  (Ctrl = 1.00 ± 0.39 N=6, Poly I:C = 10.84 ± 4.70 N=6; Mann-Whitney U test, **p < .01), Il1rn  (Ctrl = 1.00 ± 0.27 N=7, Poly I:C = 3.60 ± 1.58 N=11), Il6  (Ctrl = 1.00 ± 0.17 N=6, Poly I:C = 0.82 ± 0.12 N=7) mRNAs. H. qPCR  analyses of E17 male cortices  for: Il1α  (Ctrl = 1.00 ± 0.27 N=9, Poly I:C = 1.77 ± 0.53 N=11), Il1β  (Ctrl = 1.00 ± 0.21 N=7, Poly I:C = 1.33 ± 0.33 N=8), Il1rn  (Ctrl = 1.00 ± 0.25 N=10, Poly I:C  = 0.82 ± 0.40 N=18), Il6  (Ctrl = 1.00 ± 0.24 N=7, Poly I:C = 2.17 ± 0.43 N=8) mRNAs. I. qPCR  analyses of P90 male cortices  for: Il1α  (Ctrl = 1.00 ± 0.24 N=8, Poly I:C = 1.51 ± 0.26 N=10), Il1β  (Ctrl = 1.00 ± 0.27 N=8, Poly I:C = 1.19 ± 0.34 N=8), Il1rn  (Ctrl = 1.00 ± 0.31 N=18, Poly I:C = 1.30 ± 0.50 N=14), Il6  (Ctrl = 1.00 ± 0.27 N=7, Poly I:C = 2.40 ± 0.70 N=8) mRNAs. J. qPCR  analyses of GD9+6h female embryos  for: Il1α  (Ctrl = 1.00 ± 0.93 N=6, Poly I:C = 0.03 ± 0.00 N=4), Il1β  (Ctrl = 1.00 ± 0.61 N=5, Poly I:C = 0.17 ± 0.04 N=7), Il1rn  (Ctrl = 1.00 ± 0.25 N=9, Poly I:C = 0.33 ± 0.11 N=7), Il6  (Ctrl = 1.00 ± 0.48 N=7, Poly I:C = 0.59 ± 0.24 N=5) mRNAs. K. qPCR  analyses of E17 female cortices  for: Il1α  (Ctrl = 1.00 ± 0.31 N=5,  Poly I:C = 1.38 ± 0.20 N=12), Il1β  (Ctrl = 1.00 ± 0.30 N=5, Poly I:C = 1.05 ± 0.35 N=7), Il1rn  (Ctrl = 1.00 ± 0.55 N=6, Poly I:C  = 0.45 ± 0.22 N=6), Il6  (Ctrl = 1.00 ± 0.26 N=7, Poly I:C = 0.94 ± 0.14 N=8) mRNAs. L. qPCR  analyses of P90 female cortices  for Il1α  (Ctrl = 1.00 ± 0.08 N=5, Poly I:C = 1.32 ± 0.11 N=9), Il1β  (Ctrl = 1.00 ± 0.13 N=5, Poly I:C = 0.65 ± 0.09 N=8), Il1rn  (Ctrl = 1.00 ± 0.61 N=4, Poly I:C  = 0.85 ± 0.29 N=7), Il6  (Ctrl = 1.00 ± 0.11 N=9, Poly I:C  = 1.28 ± 0.20 N=20) mRNAs. Values are normalized over control (dashed line). Data information: Ctrl males  = white bars with blu border. Poly I:C males  = blu bars with blu border. Ctrl females  = white bars with purple border.  Poly I:C females  = purple bars with purple border. Numbers in bars indicate the number of animals (N). Bars represent mean ± SEM.",
    "ncbi_link": "CD248: 70445
Foxf2: 14238
Il1α: 16175
Il1β: 16176
Il1rn: 16181
Il6: 16193
Pdfgb: 18591
Pecam1: 18613
Tgfb1: 21803
Tgfb2: 21808
Tgfb3: 21809
Vegfa: 22339"
  },
  {
    "caption": "(C-G'') Lateral images of the cranial vessels in lyve1b:Kaede transgenic embryos with the CCV photoconverted at 36 hpf (C) and followed through to 48 hpf (D) and 60 hpf (E), while in a separate larva the PHS has been photoconverted at 36 hpf (F) and followed to 48 hpf (G). Unconverted vessels are shown in green (C-G), while photoconverted vessels are shown in red (C'-G'). The extent of lymphangioblast contribution from each source is further clarified by false colouring the overlap between red and green fluorescence (purple), with the FLS demarcated (dotted line) from the adjacent primary veins (C''-G'').",
    "ncbi_link": "Kaede: 
lyve1b: 564249"
  },
  {
    "caption": "(A-D'') Ventrolateral (A, C, D) and lateral (B) images of the cranial vessels in lyve1b:Kaede transgenic embryos with the dorsal (A) and ventral (C) portions of the VA-L photoconverted at 54 hpf and followed through to 72 hpf (B) and 78 hpf (D). Unconverted vessels are shown in green (A-D), while photoconverted vessels are shown in red (A'-D'). The extent of lymphatic and arterial contribution from the VA-L to the LFL (B'') or HA (D'') is further clarified by false colouring the overlap between red and green fluorescence (purple), with the FLS (A'', C'') and LFL (B'', D'') demarcated (dotted line) from the adjacent vessels. Schematic included for anatomical reference. Note, for all images, the overlap of red and green fluorescence in the eye (labelled E) is due to a combination of natural pigmentation and auto-fluorescence; and is not indicative of photoconverted cells (C'', white arrowheads).",
    "ncbi_link": "Kaede: 
lyve1b: 564249"
  },
  {
    "caption": "Lateral images of the CCV fixed at 36 hpf (A) and 42 hpf (B) in lyve1b:EGFP fish that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red).",
    "ncbi_link": "EGFP: 
lyve1b: 564249"
  },
  {
    "caption": "Lateral images of the PHS at 36 hpf (C), 42 hpf (D) and 48 hpf (E) in lyve1b:EGFP fish that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red). PHS Prox1 staining shown alone for all time points (C'-E') with the FLS demarcated (dotted line) from the adjacent vessels, and the positions of the PHS-LPP and PHS-LPA indicated.",
    "ncbi_link": "EGFP: 
lyve1b: 564249"
  },
  {
    "caption": "Lateral images of the VA-L at 36 hpf (F), 42 hpf (G) and 48 hpf (H) in lyve1b:EGFP fish that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red). Note the Prox1-postive (green), GFP-negative structure near to the VA-L is a prox1-expressing neuromast (NM).",
    "ncbi_link": "EGFP: 
lyve1b: 564249"
  },
  {
    "caption": "(A-H) Lateral images of the PHS fixed at 36 hpf (A-B, E-F) and 42 hpf (C-D, G-H) in lyve1b:EGFP fish that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red). These show a decrease in the number of Prox1-positive PHS ECs in the ccbe1 morpholino-injected (B, D) and sFLT4 mRNA-injected embryos (F, H) compared with control morpholino-injected (A, C) and uninjected embryos (E, G). At 42 hpf, ccbe1 morpholino-injected embryos (D) and sFLT4 mRNA-injected embryos (H) lack the PHS-LP domains present in the control embryos (C, G; large arrow heads). (I-J) Quantitation of the percentage of PHS ECs that are lymphatic progenitors relative to the total number of PHS ECs in control morpholino-injected embryos at 36 hpf (n = 27) and 42 hpf (n = 17) and ccbe1 morpholino-injected embryos at 36 hpf (n = 36) and 42 hpf (n = 12) (I) or in uninjected embryos at 36 hpf (n = 27) and 42 hpf (n = 21) and sFLT4 mRNA-injected embryos at 36 hpf (n = 26) and 42 hpf (n = 17) (J). (K) Quantitation of the total number of PHS ECs in control morpholino-injected embryos at 36 hpf (n = 27) and 42 hpf (n = 17) and ccbe1 morpholino-injected embryos at 36 hpf (n = 36) and 42 hpf (n = 12) or in uninjected embryos at 36 hpf (n = 27) and 42 hpf (n = 21) and sFLT4 mRNA-injected embryos at 36 hpf (n = 26) and 42 hpf (n = 17) ",
    "ncbi_link": "EGFP: 
ccbe1: 555629
sFLT4: 2324
lyve1b: 564249"
  },
  {
    "caption": "(L-O) Lateral images of the FLS (L, N; dotted line) or dorsolateral CCV region from where the FLS normally sprouts (M, O; dotted line) fixed at 36 hpf in lyve1b:EGFP embryos that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red). These show no change in the number of Prox1-positive lymphatic progenitors in the ccbe1 morpholino-injected (M) and sFLT4 mRNA-injected (O) embryos compared with control morpholino-injected (L) and uninjected (N) embryos. (P) Quantitation of the percentage of dorsolateral CCV ECs that are lymphatic progenitors relative to the total number of dorsolateral CCV ECs in control morpholino-injected (n = 26), ccbe1 morpholino-injected (n = 27), uninjected (n = 28) and sFLT4 mRNA-injected embryos (n = 32). (Q) Quantitation of the total number of dorsolateral region CCV ECs in 36 hpf embryos that were uninjected or injected with control morpholino (n = 26), ccbe1 morpholino (n = 27), or sFLT4 mRNA (n = 32). ",
    "ncbi_link": "EGFP: 
ccbe1: 555629
sFLT4: 2324
lyve1b: 564249"
  },
  {
    "caption": "(R-U) Dorsolateral images of the VA-L fixed at 54 hpf in lyve1b:EGFP larva that have been fluorescently immunostained with anti-PROX1 (green) and anti-GFP (red). These show that lymphatic progenitor formation still occurs within the VA-L in ccbe1 morpholino-injected (S) and sFLT4 mRNA-injected embryos (U), with Prox1 expression resembling that of controls (R, T).",
    "ncbi_link": "EGFP: 
ccbe1: 555629
sFLT4: 2324
lyve1b: 564249"
  },
  {
    "caption": "(A-B) Still images from Movie EV3 of early facial lymphatic development in a lyve1b:EGFP (A), kdrl:nlsmCherry (B) compound transgenic from 42-51.5 hpf, with the CCV-L-derived leading tip cell (green asterisk), the PHS-LP domains (orange and yellow asterisk) and the distal tip of the VA-L (purple asterisk) highlighted (A). Between 42 and 46 hpf, the PHS-LPP (orange outline) cells divide (dark blue parent cells, light blue daughter cells) before sprouting as lymphangioblasts from the PHS and fusing with the tip (pink cells) of the CCV-derived FLS (green outline) at 48 hpf (B). Cells (red) within the VA-L (purple outline) can also be seen migrating towards the now PHS-L-derived FLS tip by 48 hpf. The PHS-LPA is also shown (yellow outline).",
    "ncbi_link": "EGFP: 
nlsmCherry: 
kdrl: 796537
lyve1b: 564249"
  },
  {
    "caption": "(E-F) Still images from Movie EV4 of facial lymphatic development in a lyve1b:EGFP kdrl:nlsmCherry compound transgenic from 48-62 hpf showing that after the CCV-derived FLS fuses to the PHS-L, these take over as the leading tip cells (orange asterisks), with one PHS-L migrating anteriorly to fuse with PHS-LPA (yellow asterisk), and others migrating ventrally to fuse with the VA-L (purple asterisk) After the PHS-derived portion (orange outline) of the FLS (green outline) fuses to the VA-L (purple outline), migration of the entire facial lymphatic pauses to allow for lymphangioblast proliferation (dark blue and red parent cells, light blue and pink daughter cells) before resuming migration anteriorly along the ventral base of the eye",
    "ncbi_link": "EGFP: 
nlsmCherry: 
kdrl: 796537
lyve1b: 564249"
  },
  {
    "caption": "(A-B') Lateral (A) and ventrolateral (B, B') images of the cranial vessels in kdrl:nlsKaede;kdrl:EGFP embryos, with unconverted tissue shown in green (A-B) while photoconverted tissue is shown in red (B'). The early kdrl-positive VA-L was photoconverted in 34 hpf embryos (A), and followed through to 54 hpf (B, B'). B' is a higher magnification image of the box in B and is accompanied by a red channel only (traced photoconverted cells) image with the VA-L (dotted line) demarcated from the adjacent VA. The VA-L photoconverted cells are indicated by arrowheads.",
    "ncbi_link": "EGFP: 
nlsKaede: 
kdrl: 796537"
  },
  {
    "caption": "(C) Still images from Movie EV5 of VA-L development in a kdrl:EGFP;kdrl:nlsmCherry compound transgenic from 31-35.5 hpf. This movie shows that the VA-L begins expressing kdrl just after 32 hpf, in a manner that is isolated and independent of any neighbouring kdrl-positive tissue or vessel. Putative kdrl-positive primitive myeloid cells (light blue asterisks) can also be seen migrating along the surface of the yolk in the immediate vicinity of the VA and VA-L. (D) Still images from Movie EV6 depicting a 3D reconstruction of the 35.5 hpf timepoint from Movie EV5. A dorsal view that scrolls through the Y-stack of the VA-L is shown, which illustrates that the VA-L is closely associated with, but not connected to the VA. ",
    "ncbi_link": "EGFP: 
nlsmCherry: 
kdrl: 796537"
  },
  {
    "caption": "(E-E') Still images from Movie EV7 of VA-L development in an etv2:EGFP (E), kdrl:nlsmCherry (E') compound transgenic from 28-35.2 hpf. This movie shows that the VA-L begins expressing etv2 (E) at 29 hpf and is independent of any neighbouring vessel. kdrl expression (red arrowheads) occurs 4 hours later in the VA-L (demarcated by the green dotted line) (E').",
    "ncbi_link": "EGFP: 
nlsmCherry: 
etv2: 555766
kdrl: 796537"
  },
  {
    "caption": "(F-G') Lateral images of the cranial vessels in etv2:Kaede embryos, with unconverted tissue shown in green (F-G) while photoconverted tissue is shown in red (G'). The earliest visible form of the VA-L was photoconverted at 29 hpf (F), then followed through to 54 (G). G' is a higher magnification image of the box in G and is accompanied by a red channel only (traced photoconverted cells) image with the VA-L (dotted line) demarcated from the adjacent VA, and VA-L photoconverted cells indicated (arrowheads).",
    "ncbi_link": "Kaede: 
etv2: 555766"
  },
  {
    "caption": "(A-G) Lateral (A-B), ventrolateral (C-F) and ventral (G) images of the cranial vessels in an etv2:EGFP;kdrl:nlsmCherry compound transgenic embryo, which has had the etv2-expressing angioblast population (early VA-L) on the left lateral side of the yolk sac ablated. Images were taken at 30 hpf before (A) and after (B) ablation of the early VA-L, with the site of ablation indicated (B; blue dotted circle). Note that the LDA and VA adjacent to the VA-L become photobleached during the ablation process (B), however these were not ablated as they can be seen developing normally at 54 hpf (D). Follow-up images were taken of both the contralateral (C, E) and ablated (D, F) sides of the embryo's head at 54 hpf (C-D) and 78 hpf (E-G). Although the VA-L (light blue dotted line) is seen migrating towards the FLS (white dotted lined) on the contralateral side at 54 hpf (C), it is missing from the ablated side (D). Subsequently, the LFL (white dotted line) of the ­ablated side is short (F) compared to that of the contralateral side (E). In addition, the HA (pink dotted line) is underdeveloped on the ablated side compared to the contralateral side, as it no longer extends towards nor connects to the left ­AA1 (G). (H) Quantitation of the length of the LFL (µm) on the contralateral (control) side and on the ablated side at 78 hpf (n = 16). (I) Quantitation of the total number of cells within the LFL on the contralateral (control) side and from the ablated side at 78 hpf (n = 16). ",
    "ncbi_link": "EGFP: 
nlsmCherry: 
etv2: 555766
kdrl: 796537"
  },
  {
    "caption": "(b) Suppression of Htt103Q toxicity in yeast by Gpx1, Hyr1 (Gpx3) and mGpx1. The viability of the parental strain, Y258, and of cells overexpressing yeast GPxs was determined using spotting assays. Equal numbers of cells were serially diluted fivefold and plated on medium containing glucose to assess cell numbers and containing galactose (GAL) to induce the expression of Htt103Q and the indicated ORF.",
    "ncbi_link": "Gpx1: 2876
Gpx1: 14775
Gpx3: 2878
Hyr1: 2878"
  },
  {
    "caption": "a) Total GPx activity was measured in mGpx1-overexpressing (mGpx1) or control (WT) cell lines with (induced) or without (uninduced) Htt103Q expression. Overexpression of mGpx1 increases total GPx activity in PC12 cells (****P 0.0001 compared to uninduced controls; n = 7 per condition).",
    "ncbi_link": "Gpx1: 14775
Htt: 3064"
  },
  {
    "caption": "(b) Quantification of caspase-3/7 activation in response to Htt103Q expression in cells overexpressing mGpx1. Overexpression of mGpx1 reduces Htt103Q-mediated caspase-3/7 activation (****P 0.0001). Values represent the ratio of mGpx1 activity in cells expressing Htt103Q for 72 h compared to cells not expressing Htt103Q (n = 12 (WT); n = 9 (monomeric red fluorescent protein (mRFP)); n = 8 (mGpx1) per condition).",
    "ncbi_link": "Gpx1: 14775
Htt: 3064"
  },
  {
    "caption": "(c) Effect of the GPx mimetic ebselen on Htt103Q-mediated caspase activation. A single 10 μM dose of ebselen significantly reduced caspase-3/7 activation in Htt103Q-expressing cells (****P 0.0001). Values represent the ratio of caspase-3/7 activity in cells expressing Htt103Q for 72 h compared to cells not expressing Htt103Q. Statistical analysis was performed using an unpaired, two-tailed Mann-Whitney test (n = 12 per condition).",
    "ncbi_link": "Htt: 3064"
  },
  {
    "caption": "(d) mGpx1 overexpression (****P 0.0001) and ebselen treatment (****P 0.0001) significantly reduce Htt103Q-mediated ROS production (n = 9 per condition). Unless stated otherwise, all statistical analyses were performed using one-way analysis of variance (ANOVA) with post-hoc tests. NS, not significant. **P 0.01. All data are shown as the mean ± s.e.m.",
    "ncbi_link": "Gpx1: 14775
Htt: 3064"
  },
  {
    "caption": "(a) Pseudopupil images from wild-type flies, Huntington's disease flies and Huntington's disease flies overexpressing mGpx1 at day 10. In wild-type flies, seven rhabdomeres are visible per ommatidium. Scale bar, ∼10 μM",
    "ncbi_link": "Gpx1: 14775"
  },
  {
    "caption": "(b) Quantification of the average number of rhabdomeres per ommatidium in Huntington's disease flies with and without pan-neural mGpx1 overexpression at days 1 (n = 14 (Htt93Q); n = 9 (Htt93Q + mGpx1)), 7 (n = 7 (Htt93Q); n = 9 (Htt93Q + mGpx1)) and 10 (n = 8 (Htt93Q); n = 9 (Htt93Q + mGpx1)) after eclosion. Significant effects of genotype (F1,50 = 82.3, P = 3.82 × 10−12) and age (F2,50 = 94.3, P = 1.06 × 10−17) were observed, as well as a significant interaction between genotype and age (F2,50 = 7.76, P = 0.00116), indicating that mGpx1 reduces the rate of neurodegeneration in Htt93Q flies. Post-hoc Newman-Keuls comparisons showed significant rescue of neurodegeneration in mGpx1-expressing flies at days 1 (*P 0.05), 7 (***P 0.001) and 10 (***P 0.001). Browne-Forsythe analyses for equality of variance revealed a significant inequality of variance (P = 0.02) due to a single group (Htt93Q + mGpx1, day 1). The nonparametric Mann-Whitney test confirmed a difference at day 1 between the two groups (P = 0.03), and between Htt93Q + mGpx1 flies at days 1 and 7 (P 0.0001).",
    "ncbi_link": "Gpx1: 14775
Htt: 3064"
  },
  {
    "caption": "(c) Total locomotor activity was assessed as the average number of beam crossings per 30-min bin per fly. Htt93Qex1-expressing flies (n = 29) have reduced locomotor activity compared to controls (***P 0.001; n = 30 (WT (w118)); n = 32 (mGpx1)), which is restored by mGpx1 (**P 0.01; n = 32). Comparisons were performed by Kruskal-Wallis one-way ANOVA.",
    "ncbi_link": "Gpx1: 14775
Htt: 3064"
  },
  {
    "caption": "(d) Neurodegeneration of Pdf clock neurons was assessed using confocal microscopy in adult flies at day 7. Flies expressing Htt93Qex1 driven by Pdf-GAL4 (n = 16 brain hemispheres) showed loss of s-LNVs compared to Canton S (CS) control flies (n = 13), which was ameliorated by coexpression of mGpx1 (****P 0.0001; n = 16). Comparisons were performed by Kruskal-Wallis one-way ANOVA.",
    "ncbi_link": "GAL4: 
Gpx1: 14775
Htt: 3064
Pdf: 43193"
  },
  {
    "caption": "(A) C57BL/6 mice were inoculated with 6x105 B16Bl6 parental or dnTNF-R1 cells on day 0 and treated daily with 7µg mTNF p.l. from day 10. Tumor growth is shown as mean tumor size index (TSI) + SEM (n = 6). The line under the graph represents the treatment period.",
    "ncbi_link": "dnTNF-R1: 71609"
  },
  {
    "caption": "(B) B16Bl6 tumor growth after daily p.l. treatment with 7µg mTNF in C57BL/6J wild-type (WT), TNF-R1-/-, conditional TNF-R1 reactivation knockout (p55cneo/cneo), or p55cneo/cneo mice with Cre expression in endothelium (Flk1Cre) or all cells (DelCre). Tumor growth is shown as mean TSI + SEM (n = 7 for WT and Flk1Cre, 8 for DelCre, 9 for TNF-R1-/- and 10 for p55cneo/cneo). The line under the graph represents the treatment period.",
    "ncbi_link": "Cre: 
Flk1: 16542
p55: 21937
TNF-R1: 21937"
  },
  {
    "caption": "(C) PCR analysis for the detection of wild-type, conditional knockout (cneo) or reactivated (lox) TNF-R1 allele in whole tissues, lung endothelial cells (LECs) and lung single-cell suspension depleted of CD31+ cells.",
    "ncbi_link": "CD31: 18613
TNF-R1: 21937"
  },
  {
    "caption": "(D) Toxicity of a single i.v. bolus injection of the indicated dose of mTNF. Mean rectal body temperature + SEM and cumulative survival rates are shown (n = 4 for Flk1Cre 10µg; 6 for DelCre 10µg, Flk1Cre 10µg and p55cneo/cneo 15µg; 7 for WT 10µg; 9 for WT 8µg, 10 for DelCre 20µg; and 5 for all other groups). For continuity of the temperature graphs, dead mice were included with a temperature of 20°C.",
    "ncbi_link": "Cre: 
Flk1: 16542
p55: 21937"
  },
  {
    "caption": "(B,C) Viability of L929 parental or mCD20-expressing cells after 72h stimulation with mTNF or sc mTNF mutant Y86F fused to a BcII10 or mCD20 VHH (B) and viability of MCF7 parental or hCD20-expressing cells after 72h stimulation with hTNF or sc hTNF mutant Y87F fused to a BcII10 or hCD20 VHH (C). Cell viability was measured via an ATP luminescence assay. Each point is the mean of three replicates and error bars are SEM.",
    "ncbi_link": "hCD20: 931
mCD20: 12482"
  },
  {
    "caption": "(D) Expression of ICAM-1, E-selectin and VEGF-R2 in B16Bl6 tumor 6h after treatment, by qPCR analysis of whole tumor RNA. Error bars are SEM. ns, non-significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001 by one-way ANOVA with Bonferroni's multiple comparison test.",
    "ncbi_link": "ICAM-1: 15894
VEGF-R2: 16542
E-selectin: 20339"
  },
  {
    "caption": "(A,B) B16Bl6 tumor growth after daily p.l. treatment with 7µg mTNF, 30µg hTNF alone or in combination with 10000 IU mIFN-γ in wt C57BL/6 mice (A) or homozygous Flk1 dnIFN-γR1 transgenic mice (B). The line under the graph represents the treatment period. Tumor growth is depicted as mean TSI, error bars are SEM (n = 5).",
    "ncbi_link": "dnIFN-γR1: 15979
Flk1: 16542"
  },
  {
    "caption": "A Activity of an NF-κB reporter relative to vehicle control in human embryonic kidney cells that express TLR4 (hTLR4) or an isogenic control cell line that does not express TLR4 (null2) and were stimulated with vehicle (veh), 1 ng/mL LPS, 400 μM nickel chloride, or 25, 50 or 100 μM platinum(II) chloride and platinum(IV) chloride (n=3 independent biological replicates). B As per panel (A) but secreted IL-8 was monitored as a metric of TLR4 activation upon stimulation with 50 pg/mL LPS, 200 μM nickel chloride, 100 μM platinum(II) chloride or 100 μM platinum(IV) chloride (n=4 independent biological replicates). Data Information: For all panels actual individual data from each experiment are plotted as box (25th and 75th percentile borders; median central band) with Tukey whiskers. Statistical analyses were assessed by 2-way ANOVA: in A) hTLR4 compared to null2 cells; in B) agonist treatment compared to non-treated (nil); ns, not significant ; **, P<.01; ; ****, P<.0001 (Dunnett's test, A, B",
    "ncbi_link": "TLR4: 7099"
  },
  {
    "caption": "A IL-8 secretion in HEK cells stably expressing hTLR4 but not MD-2 (HEK-isoTLR4), transfected with empty vector (EV) or MD-2 and left untreated (nil) or treated with 1 ng/mL LPS, 200 μM nickel chloride, 2 μg/ml HMGB1, 100 μM platinum(II) chloride, 100 μM platinum(IV) chloride or 25 μM cisplatin (n=3 or 4 independent biological replicates). C IL-8 secretion in HeLa cells transfected with non-targeting (siNT) or TLR4-targeting (siTLR4) siRNA and left untreated (nil), or treated with 30 μM cisplatin (n=3 independent biological replicates). Mock cells were not subject to siRNA treatment prior. Data Information: Actual individual data are plotted as box (25th and 75th percentile borders; median central band) with Tukey whiskers (A, C) Statistical analyses were determined in comparison to nil treatments using 2-way (A, C) ns, not significant; *, P<.05; ****, P<.0001 (Dunnett's test).",
    "ncbi_link": "MD-2: 23643
TLR4: 7099"
  },
  {
    "caption": "A- HEI-OC1 cells containing a Tlr4 deletion (Tlr4-/-) were compared to HEI-OC1 non-targeting (NT) control cells and assessed for cell viability (A), AnnexinV/propidium iodide staining (B), following cisplatin treatment at the indicated concentrations (n=3 independent biological replicates). Data Information: In all panels data are presented as mean and standard deviation. Statistical comparisons to NT at the same cisplatin concentration were assessed by 2-way (A, B) *, P<.05; **, P<.0001(Bonferroni test).",
    "ncbi_link": "Tlr4: 21898"
  },
  {
    "caption": "A IL-6 secretion in HEI-OC1 cells treated with 100 pg/mL LPS or 20μM cisplatin (n=3 or 4 independent biological replicates). B IL-6 secretion in TLR4-/- cells transfected with empty vector (EV) or mouse Tlr4 (mTlr4) following treatment with 20μM cisplatin (n=6 independent biological replicates). Data information: In all panels data are presented as mean and standard deviation. Statistical comparisons to 0 hr time point were assessed by 2-way ANOVA. ns, not significant; *, P<.05; **, P<.01; ***, P<.001; ****, P<.0001 (Dunnett's test).",
    "ncbi_link": "TLR4: 21898
Tlr4: 21898"
  },
  {
    "caption": "C Il6 and Tlr4 transcript levels in HEI-OC1 cells following treatment with 20μM cisplatin for the indicated times (n=3 independent biological replicates). Data information: In all panels data are presented as mean and standard deviation. Statistical comparisons to 0 hr time point were assessed by 2-way ANOVA. ns, not significant; *, P<.05; **, P<.01; ***, P<.001; ****, P<.0001 (Dunnett's test). ",
    "ncbi_link": "Il6: 16193
Tlr4: 21898"
  },
  {
    "caption": "B Hair cell viability in larval zebrafish pre-treated with control-, tlr4ba- and/or tlr4bb-targeting morpholino oligonucleotides (MO) and subsequently treated with 15 μM cisplatin. Data information: In both panels each data point represents a score of hair cell integrity in an individual animal (taken from multiple samples per animal) with lines representing mean and standard deviation. Statistical comparisons to control morpholino (B, except as indicated in blue) were assessed by one-way ANOVA. *, P<.05; **, P<.01; ****, P<.0001 (Tukey test).",
    "ncbi_link": "tlr4ba: 403131
tlr4bb: 403132"
  },
  {
    "caption": "(A)  QRT-PCR assay of  PAX6, SOX1,   NKX2-1,  NKX2-2, TBR1  and TBR2  during dorsal (up) and  ventral (down)  neural  differentiation. (B) QRT-PCR assay of SOX1-OT V1 during dorsal (up) and ventral  (down) neural  differentiation Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, **p<0.01, ***p<0.001 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "TBR2: 8320
NKX2-1: 7080
NKX2-2: 4821
PAX6: 5080
SOX1: 6656
TBR1: 10716"
  },
  {
    "caption": "(C and D) Immunostaining assay of MAP2 (green) in control and SOX1KO cells on day 35 of dorsal neural  differentiation (C), and quantification of MAP2+ cells (D), p=0.0001. Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). ***p<0.001 versus Ctrl group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(F and G)  Immunostaining assay of GABA (green) in control and SOX1KO cells on day 35 of  ventral neural differentiation (F), and quantification of GABA+ cells (G), p=0.0001. Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). ***p<0.001 versus Ctrl group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(H and I)  Immunostaining assay of MAP2 (green) after SOX1 overexpression in V1-PAKI cells on day 35 of dorsal neural  differentiation (H), and quantification of MAP2+ cells (I), p=0.0001 (V1-PAKI), p=0.0001 (V1-PAKI+ptSOX1+dox). Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). ***p<0.001 versus Ctrl group ; ###p<0.001 versus -dox group (one-way ANOVA).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(J and K) Immunostaining assay  of GABA (green) after SOX1 overexpression in V1-PAKI cells on day 35 of  ventral neural differentiation (J), and quantification of GABA+ cells (K), p=0.0001 (V1-PAKI), p=0.0002 (V1-PAKI+ptSOX1+dox). Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). ***p<0.001 versus Ctrl group ; ###p<0.001 versus -dox group (one-way ANOVA).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(A and B) Enrichment of H3K14Ac (left) and H3K27Ac (right) on SOX1  promoter region in control and  V1-PAKI  cells on day 16 of dorsal neural differentiation (A), p=0.0046 (H3K14Ac), p=0.0223 (H3K27Ac) and  ventral neural differentiation (B), p=0.0499 (H3K14Ac), p=0.0022 (H3K27Ac). Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, **p<0.01 versus Ctrl group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(L) Enrichment of   RNA polymerase Ⅱ   on  SOX1 promoter region after Bufexamac treatment in V1-PAKI  cells on day 16 of  dorsal  (left, p=0.0007 (V1-PAKI), p=0.0002 (+Buf)) and ventral (right, p=0.0083 (V1-PAKI), p=0.0276 (+Buf)) neural  differentiation. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, **p<0.01, ***p<0.001 versus Ctrl group ; #p<0.05, ##p<0.01, ###p<0.001 versus V1-PAKI group ; (one-way ANOVA).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(B and C)  RIP  analysis for endogenous  interaction between  HDAC10 and SOX1-OT V1 on day 16 of dorsal neural  differentiation (B), p=0.0085 and ventral neural differentiation (C), p=0.0152. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, **p<0.01, ***p<0.001 versus IgG group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(D and E) Enrichment of HDAC10 on SOX1 promoter region in control and V1-PAKI cells on day 16 of  dorsal neural  differentiation (D), p=0.0052 and ventral neural  differentiation (E), p=0.0001. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, **p<0.01, ***p<0.001 versus Ctrl group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(G and H)  Immunostaining assay of SOX1  (red) after SOX1-OT V1, SOX1-OT V1-5P or SOX1-OT V1-3P overexpression in V1-PAKI cells on day 16 of  dorsal neural differentiation (G), and quantification of SOX1+ cells (H), p=0.0001 (V1-PAKI), p=0.0001 (ptV1+dox), p=0.0001 (pt5P+dox). Scale bar, 100 μm. (I and J) Immunostaining assay of SOX1 (red) after  SOX1-OT V1, SOX1-OT V1-5P or SOX1-OT V1-3P overexpression in V1-PAKI cells on day 16 of ventral neural  differentiation (I), and quantification of SOX1+ cells (J), p=0.0001 (V1-PAKI), p=0.0001 (ptV1+dox), p=0.0001 (pt5P+dox). Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). *p<0.05, ***p<0.001 versus Ctrl group ; #p<0.05, ##p<0.01, ###p<0.001 versus -dox group (one-way ANOVA).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(A and B) Immunostaining assay of ASCL1 (green) in control, V1-PAKI and SOX1KO cells on day 25 of dorsal neural differentiation (A), and quantification of ASCL1+ cells (B), p=0.0021 (V1-PAKI), p=0.0024 (SOX1KO). Scale bar, 100 μm. (C and D)  Immunostaining assay  of ASCL1 (green) in control, V1-PAKI  and SOX1KO cells on day 25 of ventral neural differentiation (C), and quantification of ASCL1+ cells (D), p=0.0003 (V1-PAKI), p=0.0004 (SOX1KO). Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). **p<0.01, ***p<0.001 versus Ctrl group (unpaired two-tailed Student's t-test).",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(E and F) Immunostaining assay  of ASCL1  (green) after SOX1 overexpression in V1-PAKI cells on day 25 of  dorsal neural differentiation (E), and quantification of ASCL1+ cells (F), p=0.0001 (V1-PAKI), p=0.0001 (ptSOX1+dox). Scale bar, 100 μm. (G and H)  Immunostaining assay  of  ASCL1 (green) after SOX1 overexpression in V1-PAKI cells on day 25 of ventral neural differentiation (G), and quantification of  ASCL1+ cells (H), p=0.0001 (V1-PAKI), p=0.0001 (ptSOX1+dox). Scale bar, 100 μm. (I and J)  Immunostaining assay of MAP2 (green) after  ASCL1 overexpression in V1-PAKI cells on day 35 of dorsal neural  differentiation (I), and quantification of MAP2+ cells (J), p=0.0001 (V1-PAKI), p=0.0001 (ptASCL1+dox). Scale bar, 100 μm. (K and L)  Immunostaining assay  of GABA (green) after  ASCL1  overexpression in V1-PAKI  cells on day 35 of ventral neural differentiation (K), and quantification of GABA+ cells (L), p=0.0001 (V1-PAKI), p=0.0001 (ptASCL1+dox). Scale bar, 100 μm. Data information: Data are presented as mean ±SEM from three independent experiments (n=3). ***p<0.001 versus Ctrl group ; ###p<0.001 versus -dox  group (one-way ANOVA).",
    "ncbi_link": "ASCL1: 429
SOX1: 6656"
  },
  {
    "caption": "(A and B) Immunostaining assay  of SOX1 (red) in control, V1-PAKI  and  SOX1KO cells on day 40 of dorsal (A) and  ventral (B) organoids differentiation. Scale bar, 100 μm. (C) Immunostaining assay of MAP2  (green) in control, V1-PAKI  and SOX1KO cells on day 40 of dorsal organoids differentiation. Scale bar, 100 μm. (D)  Immunostaining assay  of GABA (green) in control, V1-PAKI and SOX1KO cells on day 40 of  ventral organoids  differentiation. Scale bar, 100 μm.",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "(E and F) Immunostaining assay  of SOX1  (red) after SOX1-OT V1 overexpression in V1-PAKI cells on day 40 of dorsal (E) and ventral (F) organoids differentiation. Scale bar, 100 μm. (G)  Immunostaining assay of MAP2  (green) after SOX1-OT V1 overexpression in V1-PAKI cells on day 40 of  dorsal organoids differentiation. Scale bar, 100 μm. (H) Immunostaining assay  of GABA (green) after SOX1-OT V1 overexpression in V1-PAKI  cells on day 40 of  ventral organoids differentiation. Scale bar, 100 μm.",
    "ncbi_link": "SOX1: 6656"
  },
  {
    "caption": "B) Representative IRM and TIRF microscopy images showing microtubule positions and Tau-meGFP intensities for different PTM variants (grey: wild type; blue: Ttll1-/-; yellow: Ttll7-/-; green: Ttll1-/-Ttll7-/-; pink: Atat1‑/‑). In the last column, false-coloured TIRF images highlight differences of Tau-meGFP intensities on different types of microtubules (Movie EV1). C) Quantification of integrated intensity of Tau-meGFP on GMPCPP microtubules in three independent sets of experiments performed with independently purified tubulin samples. Single assays (Fig EV2A) of one experiment were combined after normalisation to the wild-type microtubule values (A.U. = arbitrary units). Each data point represents the normalised fluorescence intensity value of one microtubule. D) Summary quantification the three independent experiments shown in (C). Each point is a normalised mean of the triplicates, error bars represent standard deviation.",
    "ncbi_link": "Atat1: 73242
Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "E) Saturation curve of increasing concentration Tau-mCherry binding to GMPCPP wild-type and Ttll1-/-Ttll7-/- microtubules. Each data point is shown as mean ± standard deviation of the raw integrated intensity values (A.U. ×104) of three experiments with independently purified tubulin samples (Fig EV2D). Dissociation constants Kd and R2 coefficient from non-linear fits of each microtubule type are indicated below the plot.",
    "ncbi_link": "Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "Confirmation of ALDH1A3 mRNA levels of gene expression in pro-invasive (Ren13 and Ren86) and non-pro-invasive (Ren28 and Ren50) tumors. Average ± SD of 4-6 independent replicates per group were analyzed by Mann-Whitney test *p < 0.05 **p < 0.01.",
    "ncbi_link": "ALDH1A3: 220"
  },
  {
    "caption": "(a) MDCK/pGFP-LC3 cells infected with a wild-type or ΔactA2 strain of L. monocytogenes were stained with an anti-Listeria antibody (red) and rhodamine phalloidin (stains F-actin; light blue). Scale bars, 10 μm. Arrowheads indicate GFP-LC3-positive bacteria. (b) High magnification of framed images in a, and graphs show intensity of the fluoresence signal along the arrow. (c) Quantification of the number of GFP-LC3-positive bacteria shown in a. Data are mean ± s.e.m. At least 500 bacteria were counted in each experiment (n = 7 and 6 experiments at 2 and 4 h, respectively).",
    "ncbi_link": "actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(d) LC3 levels in infected MDCK cells. MDCK cells were infected with wild-type or ΔactA2 bacteria for the indicated times. EBSS (Earle's balanced salt solution, a starvation medium) and rapamycin (100 μg ml−1) were used as controls.",
    "ncbi_link": "actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(e-f) Intracellular survival of wild-type or ΔactA2 bacteria in MDCK cells (e; n = 8), MDCK cells treated with 10 mM 3-MA (f; n = 4),",
    "ncbi_link": "actA2: 17175811"
  },
  {
    "caption": "(e-h) Intracellular survival of wild-type or ΔactA2 bacteria in atg5+/+ MEF cells (g; n = 8 and 7 for wild-type and ΔactA2, respectively) or atg5−/− MEF cells (h; n = 4 and 3 for wild-type and ΔactA2, respectively). Data are presented as the number of colony-forming units (CFU) relative to that at 30 min after infection, and are mean ± s.e.m. WT, wild type.",
    "ncbi_link": "actA2: 17175811
atg5: 11793"
  },
  {
    "caption": "(b, c) Quantification of the number of GFP-LC3-positive bacteria (b) or actin-accumulating bacteria (c). Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n = 3 experiments).",
    "ncbi_link": "LC3: 84557"
  },
  {
    "caption": "(d) Colocalization of ubiquitin with ΔactA2. MDCK/pGFP-LC3 cells infected with ΔactA2 bacteria were stained with an anti-Listeria antibody (blue) and anti-ubiquitin antibody (red). Scale bars, 10 μm. Arrowheads indicate GFP-LC3-positive or ubiquitin-positive bacteria. (e) High magnification of framed image in d, and the graph shows the intensity of the fluorescence signal along the arrow. (f) Quantification of the number of GFP-LC3-positive, ubiquitin-positive or GFP-LC3- and ubiquitin-positive bacteria. Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n = 3 experiments).",
    "ncbi_link": "actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(g) Immunogold electron micrograph of MDCK/pGFP-LC3 cells infected with ΔactA2. Gold particles of 5 nm (arrowheads) indicate GFP-LC3, and gold particles of 10 nm (arrows) indicate ubiquitin. Scale bars, 0.5 μm.",
    "ncbi_link": "actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(h) Kinetics of the generation of GFP-LC3-positive or ubiquitin-positive bacteria. Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n = 3 experiments). *P 0.001. (i) Quantification of the number of ubiquitin-positive or GFP-LC3-positive bacteria. MDCK/pGFP-LC3 cells infected with wild-type or ΔactA2 bacteria were untreated or treated with 3-MA (10 mM). Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n ≥ 3 experiments). Ub, ubiquitin. WT, wild type.",
    "ncbi_link": "actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(a) Quantification of the number of ubiquitin-positive, p62-positive or GFP-LC3-positive bacteria. MDCK/pGFP-LC3/pp62-3×Myc cells were infected with a wild-type or ΔactA2 strain of L. monocytogenes for 2 h. Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n = 6 experiments).",
    "ncbi_link": "p62: 
actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(b) Colocalization of p62 with ΔactA2. MDCK/pGFP-LC3/pp62-3×Myc cells were stained with an anti-ubiquitin antibody (light blue), anti-Myc antibody (red), DAPI (white) and anti-GFP-LC3 (green). Scale bar, 10 μm. Arrowheads indicate GFP-LC3-, ubiquitin- or p62-positive bacteria.",
    "ncbi_link": "p62: 
actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(c) Quantification of the number of ubiquitin-positive, p62-positive or GFP-LC3-positive bacteria. p62−/−/p62 cells were infected with ΔactA2 bacteria for 2 h. Data are mean ± s.e.m., at least 500 bacteria were counted in each experiment (n = 6 and 3 experiments for p62−/− and p62−/−/p62, respectively)",
    "ncbi_link": "p62: 
actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(d, e) Intracellular survival of wild-type or ΔactA2 bacteria in p62−/− cells (d) or p62−/−/p62 cells (e; colony-forming units, CFU, relative to CFU 30 min after infection). Data are presented as mean ± s.e.m. (n ≥ 4 experiments).",
    "ncbi_link": "p62: 
actA2: 17175811"
  },
  {
    "caption": "(g) Generation of p62-3×Myc mutants in p62−/− cells.",
    "ncbi_link": "p62: "
  },
  {
    "caption": "(h) Quantification of the number of GFP-positive or GFP-LC3-positive bacteria. p62−/−/p62 (wild type, ΔLIR, ΔUBA, ΔLIR-ΔUBA or K7AD69A) cells were infected with ΔactA2 bacteria and stained with anti-bacteria and anti-Myc antibodies (Supplementary Information, Fig. S4e). Data are mean ± s.e.m., at least 500 LC3 were counted in each experiment (n = 3 experiments). P 0.001 versus p62-positive LC3 in p62−/−/p62 wild-type cells, P 0.001 versus GFP-p62-positive bacteria in p62−/−/ubiquitinwild-type cells. Ub, ubiquitin. WT, wild type. A full scan of g is shown in Supplementary Information, Fig. S7.",
    "ncbi_link": "p62: 
actA2: 17175811
LC3: 84557"
  },
  {
    "caption": "(b-e) The series of pEGFP-ActA-Q79C constructs was transfected into COS-7 cells. Cells were fixed with 4% Paraformaldehyde after 18 h and stained with an anti-Arp2 antibody (b), an anti-VASP antibody (c), an anti-ubiquitin antibody (d) or an anti-p62 antibody (e; red). Scale bars, 10 μm. Arrowheads indicate Arp2-, VASP-, ubiquitin- or p62-positive Q79C. Ub, ubiquitin.",
    "ncbi_link": "ActA: 17175811"
  },
  {
    "caption": "(b-e) The series of pEGFP-ActA-170 constructs was transfected into COS-7 cells. Cells were fixed with 4% Paraformaldehyde after 14 h and stained with an anti-Arp2 antibody (b), an anti-VASP antibody (c), an anti-ubiquitin antibody (d) or an anti-p62 antibody (e; red). Scale bars, 10 μm. Arrowheads indicate Arp2-, VASP-, ubiquitin- or p62-positive 170. Ub, ubiquitin.",
    "ncbi_link": "ActA: 17175811"
  },
  {
    "caption": "Ala/Phe substitutions of aa 239-244 were introduced in the NCT ectodomain to evaluate the role of this region in the regulation of GSEC processivity. Aβ38, Aβ40, and Aβ42 levels present in the conditioned medium collected from KO NCT MEF cells rescued with WT or respective mutant NCT GSECs and transiently expressing with APPC99 were quantified by ELISA. Aβ(38+40)/42 ratio was calculated to determine GSEC processivity towards APPC99. DKO PSEN1/PSEN2 MEFs rescued with the indicated FAD PSEN1 mutant and transduced with APPC99 were used as references.",
    "ncbi_link": "PSEN1: 5663
PSEN2: 5664"
  },
  {
    "caption": "Aβ profiles (% contribution of individual Aβ37, Aβ38, Aβ40, and Aβ42 peptides to the total Aβ levels (Aβ37+38+40+42)) in the conditioned medium collected from WT or mutant (NCT) MEF cells lines co-expressing WT or mutant APPC99 substrates were assayed by ELISA. Schematic models of the tested GSEC-APP complexes are shown.",
    "ncbi_link": "NCT: 59287"
  },
  {
    "caption": "(b) Images of MCF10A cells expressing GFP-LC3G120A and mCherry-LC3; note no recruitment of GFP-LC3G120A to the entotic vacuole. Scale bar, 15 μm. (c) LC3 is recruited from the host-cell cytosol onto the entotic vacuole membrane. Data points are the mean fluorescence intensity of GFP-LC3 on vacuoles versus cytoplasm for two independent cell-in-cell structures (see Supplementary Movie S2).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(c,d) Quantification of LC3 recruitment (c), and cell fate (d), of mixed cell-in-cell structures for which host or internalized cells were treated with ATG5 siRNA. Data represent mean±s.e.m.from three separate experiments; n, total number of structures analysed; *P0.01, **P0.004.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(a) The fate of internalized cells (control MCF10A and MCF10A expressing E7 and Bcl2) was measured with and without autophagy inhibition. Data show the percentage of internalized cell release with autophagy inhibition, compared with each control without autophagy inhibition; mean±s.e.m. from at least three independent experiments (total cell numbers analysed: ATG5 siRNA, 261 cells; Bcl2 ATG5 siRNA, 97 cells; 3-MA, 170 cells; Bcl2 3-MA, 112 cells); *P0.05, **P0.02.",
    "ncbi_link": "ATG5: 9474
Bcl2: 596
E7: 1489445"
  },
  {
    "caption": "(b) Effects of Y27632, 3-MA and VPS34 and ATG5 siRNA on MCF10A cell-in-cell formation in suspension for 7 h; >300 cells per condition were scored for cell-in-cell formation; ±s.e.m.from three independent experiments; **P0.004.",
    "ncbi_link": "ATG5: 9474
VPS34: 5289"
  },
  {
    "caption": "(c) Representative images of an MCF10A E7+Bcl2 cell-in-cell structure formed in soft agar. The arrow marks LC3 recruitment around internalized cells. Scale bar, 5 μm.",
    "ncbi_link": "Bcl2: 596
E7: 1489445"
  },
  {
    "caption": "(d) Quantification of MCF10A E7+Bcl2 cell-in-cell structures 48 h after seeding into soft agar (white bars), and colony formation after 2 weeks (grey bars). Data represent mean±s.e.m.from three independent experiments; *P0.03, **P0.004, ***P0.001. (e) Representative wells for data in d. The insets show higher magnifications.",
    "ncbi_link": "Bcl2: 596
E7: 1489445"
  },
  {
    "caption": "(f) Quantification of MCF10A E7+Bcl2 colony formation with Atg5 knockdown with two separate siRNAs. Data represent mean±s.e.m.from three independent experiments; *P0.001. (g) Representative wells for data in f. The insets show higher magnifications. See also Supplementary Movie S6.",
    "ncbi_link": "Atg5: 9474
Bcl2: 596
E7: 1489445"
  },
  {
    "caption": "(a) Time-lapse images of MCF10A cell-in-cell structures with an internalized cell that undergoes apoptosis. The arrows mark the recruitment of LC3 around apoptotic fragments (see Supplementary Movie S7). Scale bar, 10 μm. (b) Quantification of LC3 recruitment to apoptotic internalized cells in the presence of ATG5 or FIP200 siRNA; n, number of cells analysed; ***P0.0001, chi-squared test.",
    "ncbi_link": "ATG5: 9474
FIP200: 9821"
  },
  {
    "caption": "(c) Apoptotic U937 cells expressing H2B-mCherry phagocytized by J774 macrophages expressing GFP-LC3. Confocal images show LC3 recruitment to an engulfed corpse (arrow; see Supplementary Movie S8). Scale bar, 15 μm. (d) Quantification of LC3 recruitment to apoptotic phagosomes in control and Atg5-shRNA-expressing cells; ***P0.0001, chi-squared test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) Representative images of apoptotic cell phagocytosis and degradation in control (n=21) and Atg5 shRNA (n=21) J774 GFP-LC3 cells; ***P0.0001, chi-squared test. Scale bar, 10 μm. See also Supplementary Fig. S3.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Representative images of a J774 macrophage expressing GFP-LC3 incubated in media containing red dextran. The arrow marks LC3 recruitment to a dextran-containing macropinosome. Scale bar, 2 μm. (b) Quantification of LC3 recruitment to macropinosomes in control and Atg5 shRNA J774 macrophages; n, number of macropinosomes analysed; ***P0.0001, chi-squared test. See Supplementary Movie S9.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c) Representative image of LC3 recruitment to macropinosomes (arrows) in MCF10A cells expressing GFP-LC3 incubated with red dextran. Scale bar, 2 μm. (d) Quantification of LC3 recruitment to macropinosomes in MCF10A cells treated with siRNA against FIP200 or ATG5; n, number of macropinosomes analysed; ***P0.0001, chi-squared test.",
    "ncbi_link": "ATG5: 9474
FIP200: 9821"
  },
  {
    "caption": "(c) Representative images of apoptotic phagosomes in embryos from control-RNAi- or bec-1-RNAi-fed worms. The insets show higher magnifications of the areas outlined in the main panels. (d) Quantification of GFP::LGG-1- and mCherry::RAB-5-positive phagosomes in control- or bec-1-RNAi embryos determined by time-lapse imaging. Control, 21 embryos, 52 phagosomes; bec-1, 9 embryos, 25 phagosomes; ***P0.0001, chi-squared test.",
    "ncbi_link": "bec-1: 177345"
  },
  {
    "caption": "(e) Representative DIC images from control- and bec-1-RNAi embryos at different stages of development (minutes after first division). The yellow arrowheads mark apoptotic corpses. Scale bar, 10 μm. (f) Quantification of apoptotic corpses in control- and bec-1-RNAi embryos; data show ± s.d.; ***P0.0001.",
    "ncbi_link": "bec-1: 177345"
  },
  {
    "caption": "(g) Representative images of CED-1::GFP embryos with control or bec-1 RNAi. The yellow arrowheads mark engulfed corpses surrounded by CED-1::GFP. Scale bar, 5 μm.",
    "ncbi_link": "bec-1: 177345"
  },
  {
    "caption": "(E) Schematic illustration of the hCST collateral into the cervical cord and confocal images of hCST collaterals (green), stained for vGlut (red) and vGAT (blue) 21 days following spinal cord injury. Insets represent 3D views generated in Imaris of the deconvolved confocal image. (F) Quantification of bouton density and characterization of bouton between control and FGF22 overexpressing mice (n = 4-5 mice per group). (",
    "ncbi_link": "FGF22: 67112"
  },
  {
    "caption": "(C) Schematic illustration and representative confocal image for vGlut2-Cre neuronal labeling (cyan) and hCST collaterals (white). Insets represent 3D views generated in Imaris of the confocal image. Quantification of hCST contacts onto vGlut neurons (n = 4-6 mice per group).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(C) Schematic illustration of the hCST collateral exiting into the cervical cord and confocal images showing exiting hCST collaterals in control (left panel) and FGF22 treated (right panel) mice and quantification of the number of hCST collaterals that enter the cervical grey matter 3 weeks following spinal cord injury. (n = 6 mice per group).",
    "ncbi_link": "FGF22: 67112"
  },
  {
    "caption": "(E) Schematic illustration of the boutons on cervical hCST collateral and confocal images showing putative synaptic boutons (arrows) on newly formed cervical hCST collaterals at 3 weeks following spinal cord injury in a FGF22 (right) and a control (left) mice. Quantification of bouton density in control and FGF22 treated mice. (n = 6 mice per group",
    "ncbi_link": "FGF22: 67112"
  },
  {
    "caption": "(G) Confocal images showing contacts between CST collaterals (red) and long propriospinal neurons (magenta) transduced with FGF22 (cyan). Quantification of the contacts between the hCST collaterals and long propriospinal transduced with FGF22 or control virus (DP refers to double positive cells). Insets on the right are magnification of the boxed area on the left. (n = 6 mice per group).",
    "ncbi_link": "FGF22: 67112"
  },
  {
    "caption": "(C) Timeline of the experiment with FGF22 injection right after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in controls (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi"), 14dpi and 21dpi after spinal cord injury. (n = 9-10 mice per group). (D) Timeline of the experiment with FGF22 injection 24hrs after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in control (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi" or 2 days "2dpi for the late treatment), 14dpi and 21dpi after spinal cord injury. (n = 9-10 per group). (E) Timeline of the experiment with FGF22 injection 5 days after the onset of the spinal cord lesion (top). Quantification of the functional recovery in the regular (middle) and irregular (bottom) ladder rung test in control (grey) and FGF22 (orange) treated mice at baseline, at 3 days post injury ("3dpi"), 14dpi and 21dpi after spinal cord injury. (n = 9-10 per group).). (F",
    "ncbi_link": "FGF22: 67112"
  },
  {
    "caption": "(C) RPL26  mono- and  di-UFMylation  is lost in Chlamydomonas reinhardtii (Cr) uba5  and ufl1  mutants. Liquid TAP cultures were either left untreated (control) or treated for 24 hours with 200 ng/mL tunicamycin. Protein extracts were analyzed by immunoblotting  with anti-UFM1  antibodies. Total proteins were analyzed by Ponceau S staining. 12 hours and 24 hours treatment replicates are shown in Fig. S3C. Right Panel, Quantification of UFMylated RPL26. RPL26 mono-UFMylated; RPL26-(UFM1)2: RPL26 di-UFMylated.",
    "ncbi_link": "uba5: 5719339
ufl1: 5717654"
  },
  {
    "caption": "(D) Chlamydomonas reinhardtii   (Cr) UFMylation  pathway mutants are sensitive to ER  stress triggered by tunicamycin. Liquid TAP cultures of wild type (wt), uba5, ufl1  and ire1  mutants were either left untreated (control) or treated for 3 days with 200 ng/mL of tunicamycin. Left panel, representative images of control and treated liquid cultures taken 3-days after incubation. Middle Panel, optical density (OD) 600  (OD600) quantification of each genetic background under control conditions. Bars represent the mean (± SD) of 5 biological replicates. Two-tailed unpaired t-tests were performed to analyze the differences between wild type and mutants. Right Panel, normalized OD600  quantification of each genetic background under tunicamycin  treatment conditions. Bars represent the mean (± SD) of 5 biological replicates. Two-tailed unpaired t-tests were performed to analyze the differences between wild type and mutants. ns, p-value > 0.05; ***, p-value < 0.001. BR: Biological Replicate.",
    "ncbi_link": "ire1: 5726847
uba5: 5719339
ufl1: 5717654"
  },
  {
    "caption": "(G)  AtC53cAIM forms more GFP-ATG8A colocalizing  puncta upon ER  stress. Upper Panel, representative confocal  images of transgenic Arabidopsis  seedlings co-expressing C53-mCherry  (magenta), C53sAIM-mCherry and C53cAIM-mCherry  with GFP-ATG8a  in c53  mutant background under normal condition and after tunicamycin  stress. 6-day old seedlings were incubated in liquid 1/2 MS medium with 1% sucrose  supplemented with DMSO  as control or tunicamycin  (10 μg/ml) for 6 hours before imaging. Scale bars, 30 μm. Inset scale bars, 10 μm. Right Panel, Quantification of the C53-autophagosomes  (C53-APG) per normalized Z-stacks. Bars represent the mean (± SD) of at least twenty roots from 3 biological replicates for each genotype and treatment. Unpaired two-samples Wilcoxon test with continuity correction was performed to analyze the differences between wild type and mutants. ***, p-value < 0.001.",
    "ncbi_link": "ATG8a: 
GFP: 
mCherry: 
c53: 830574
C53: 830574"
  },
  {
    "caption": "A Relative  mRNA  expression levels of indicated CLEAR network genes in HCT116 cells treated as indicated ((NEN (N) 1.2 µM; Domperidone (Domp, D), Imipramine (Imi), Desipramine (Desi) and Amitriptyline  (Ami), each 30 µM; Clomipramine  (Clomi) 20 µM), determined by qPCR. Data information: In (A) (first (TFE3) and third (CD68) graph (N=3); second (TFE3) and fourth (CD68) graph (N=5, besides NEN+Clomi  (N=4) and NEN+Desi  (N=4)) data are presented as mean (SD) and were analyzed by a one-way ANOVA with Tukey post-hoc test. In the second and the fourth graph, significance is indicated for the comparison of combinatorial treatments (NEN+TCAs) to controls (Ctrl). * p< 0.05; ** p< 0.01;*** p< 0.001; **** p < 0.0001.",
    "ncbi_link": "CD68: 968
TFE3: 7030"
  },
  {
    "caption": "C Relative UPP1 mRNA expression  levels in  HCT116 cells either transfected with control (siCtrl) or combined  TFE3- and MITF- targeting (siTFE3/siMITF) siRNAs and treated as indicated (NEN  (N) 1.2 µM, Domperidone  (D) 30 µM, ISRIB 1 µM), determined by qPCR. Data information: data (N=3) are presented as mean (SD) and were analyzed by two -way ANOVA with Tukey post-hoc test",
    "ncbi_link": "MITF: 4286
TFE3: 7030
UPP1: 7378"
  },
  {
    "caption": "F  Immunoblot  of HCT116 whole cell lysate using antibodies against the indicated proteins upon treatment of the cells as indicated for 16h (NEN (low) 0.6 µM or NEN (High) 1.2 µM, Domperidone  (Domp) 30 µM) Cells were transfected either with control (siCtrl) or UPP1-targeting (siUPP1) siRNAs 48h prior to treatment.",
    "ncbi_link": "UPP1: 7378"
  },
  {
    "caption": "H Ratio of  toxicity and viability of HCT116 spheroids (3D) treated as indicated (NEN 1.2 µM, Imipramine (Imi), Desipramine (Desi), Amitriptyline (Ami), each 30 µM). Cells were transfected with control (siCtrl) or  UPP1-targeting (siUPP1) siRNAs 24h prior to spheroid formation. Data information: data (N=3) are presented as mean (SD) and were analyzed by two -way ANOVA with Tukey post-hoc test",
    "ncbi_link": "UPP1: 7378"
  },
  {
    "caption": "A Relative mRNA expression levels of DHODH  in HCT116  cells treated as indicated for 16h (NEN (N) 1.2 µM, Domperidone (Domp, D), Imipramine (Imi), Desipramine (Desi), Amitriptyline  (Ami), each 30 µM, Clomipramine (Clomi) 20 µM). Data information: , data are presented as mean (SD) (N=3) and were analyzed by Kruskal-Wallis with Dunn´s post-hoc test (A, left graph), one-way ANOVA with Tukey post-hoc test (A, right graph) In (A), significance is indicated for the comparison of the different treatments to controls. ** p < 0,01; **** p < 0,0001.",
    "ncbi_link": "DHODH: 1723"
  },
  {
    "caption": "D) Percentage schizonts (from total number of schizonts in a well +/- s.d.) located in the different hepatocyte sub-populations by NF54, NF135, NF175 on day 3 p.i.. Each dot represents a biological replicate. For each parasite line, at least 100 schizonts were characterized from 2x 96 wells for the final percentage. The values from three biological replicates were used in a RM ANOVA test followed by a Tukey's multiple comparison test. Percentage of schizonts in Z1/hGK++/hGS- hepatocytes is not different between the three parasite strains. Percentage of schizonts in Z2/hGK+/hGS- for NF54 is significantly different from NF135 (p = 0.0015) and NF175 (p = 0.0015). Percentage of schizonts in Z3/hGK-/hGS+ hepatocytes for NF54 is significantly different from NF135 (p = 0.0002) and NF175 (p = 0.0.0002). Data information: * p <0.05; ** p < 0.005; *** p <0.001; **** p <0.0001",
    "ncbi_link": "hGK: 2645
hGS: 2752"
  },
  {
    "caption": "F) Size of schizonts in Z1/hGK++/hGS-, Z2/hGK+/hGS- and Z3/hGK-/hGS+ hepatocytes on day 3 post invasion for the different Pf strains. For each parasite line, at least 100 schizonts were measured from each biological replicate. The median values +/- s.d. (as the sizes within the population is not normally distributed) from three biological replicates were used in a RM ANOVA test followed by a Tukey's multiple comparison test. Data information: * p <0.05; ** p < 0.005; *** p <0.001; **** p <0.0001",
    "ncbi_link": "hGK: 2645
hGS: 2752"
  },
  {
    "caption": "D) Median sizes (+/- s.d.) of NF135 (green), NF175 (purple) and NF54 (blue) schizonts divided based on the presence (solid line) or absence (dashed line) of hGS staining pattern based on high content fluorescence microscopy from three different liver donors where each donor has at least 100 schizonts were measured for each of three biological replicates. A two-way RM ANOVA was performed on the median followed by a Tukey's multiple comparisons test. The significant differences between hGS+ and hGS- population within a strain is showed with asterisks (* p <0.05; ** p < 0.005; *** p <0.001; **** p <0.0001). See Appendix Fig S1 for the raw measurements.",
    "ncbi_link": "hGS: 2752"
  },
  {
    "caption": "B) Size difference between the GS positive (closed circle) and negative (open circle) NF135 schizonts after treatment of AIP. Each dot represents the median of a biological replicate where ≥100 schizonts were measured. Three biological replicates were performed with the median from each plotted +/- s.d.. A two-way ANOVA was performed followed by a Dunnett's multiple comparison test with *** = 0.0002 and **** = 0.0001.",
    "ncbi_link": "GS: 2752"
  },
  {
    "caption": "C, D Culture dynamics of non‐infected (C) or phage‐infected (D) cultures. Curves depict culture dynamics of strains lacking BREX (black) and BREX‐containing (red) strains of B. subtilis BEST7003, as well as a BREX‐containing strain where the pglX methylase was deleted (green). Axes and error bars are as in Fig .",
    "ncbi_link": "pglX: "
  },
  {
    "caption": "A Western blot  analysis of VSV-G protein levels in Ifnar1+/+ or Ifnar1-/- MEF cells infected with  VSV (MOI=1.0, 24 hrs) immediately after addition of NaCl (+34 mM). Data information: are representative of at least two biological replicates",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "F RT-qPCR analysis of Ifit1,  Isg54 and Isg15 mRNA levels in HEK293T pretreated with additional NaCl  (+34 mM) for 12 hrs and then treated with IFNα (1,000 IU/ml) as indicated. Data information: Data represent mean and SD of three biological replicates, and p values were calculated using two-tailed unpaired Student's t-test For all statistical testing: NS, not significant (p > 0.05), **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "Ifit1: 3434
Isg54: 3433
Isg15: 9636"
  },
  {
    "caption": "N Survival curves of 8-week-old Rsad2+/+ or Rsad2-/- mice administrated with an NSD or HSD for 7 days and then intraperitoneally infected with VSV (1×108 PFU per gram body mouse, n=10). Data information: Data (N) show the mean and SEM of ten biological replicates, and p value was calculated using logrank (Mantel-Cox) tests. For all statistical testing: NS, not significant (p > 0.05), **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "Rsad2: 58185"
  },
  {
    "caption": "B Western blot  analysis of FH-Viperin protein in stable FH-Viperin-expressing  HeLa  cells pretreated with additional NaCl  (+34 mM) and then treated with  CHX (50 μM) for 6 and 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "FH: 
Viperin: 91543"
  },
  {
    "caption": "J Western blot analysis of Viperin in 2fTGH cells transfected with control shRNAs (shCtrl) or shRNAs against USP33 (shUSP33) and then treated with IFNα (1,000 IU/ml) for different times. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "M Western blot  analysis of Viperin protein in Usp33-/- MEF  cells transfected with FH-USP33 (wild type, WT; C194S and H673Q, DM) and then stimulated with mIFNβ (500 IU/ml) for 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "FH: 
Usp33: 170822
USP33: 170822"
  },
  {
    "caption": "O Western blot analysis of  Flag-Viperin in stable Flag-Viperin-expressing HEK293T  cells transfected with shCtrl or shUSP33 and then treated with CHX (50 μM) as indicated. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Flag: 
Viperin: 91543
USP33: 23032"
  },
  {
    "caption": "D  Immunoprecipitation analysis of Viperin ubiquitination in HEK293T cells co-transfected with  Flag-Viperin, HA-Ub  and shUSP33, then treated with additional NaCl (+34 mM) for 12 hrs. Data information: Data are representative of at least two biological replicates",
    "ncbi_link": "Flag: 
HA: 
Viperin: 91543
USP33: 23032"
  },
  {
    "caption": "E  Western blot  analysis of  Viperin levels in  2fTGH cells transfected with shCtrl or shUSP33 and then infected with VSV (MOI=1.0, 12 hrs) immediately after addition of  NaCl  (+34 mM). Data information: Data are representative of at least two biological replicates",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "G RT-qPCR analysis of VSV RNA levels in 2fTGH cells transfected with shCtrl or shUSP33 and then infected with VSV (MOI=1.0, 24 hrs) immediately after addition of NaCl (+34 mM). Data information: Data (G) represent mean and SD of three biological replicates, and p values were calculated using two-tailed unpaired Student's t-test For all statistical testing: NS, not significant (p > 0.05). ***p < 0.001.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "I Survival curves of 8-week-old Usp33-/- mice fed an NSD  (0.5% NaCl) or HSD (4% NaCl) for 7 days and then infected with VSV (1x108 PFU per gram body mouse, n=10). Data information: ; Data (I) show mean and SEM of ten biological replicates, and p value was calculated using logrank (Mantel-Cox) tests. For all statistical testing: NS, not significant (p > 0.05). ***p < 0.001.",
    "ncbi_link": "Usp33: 170822"
  },
  {
    "caption": "G Immunoprecipitation analysis of  ubiquitination of Flag-USP33  in p97-WT or p97-KO 2fTGH cells co-transfected with  Flag-USP33 and HA-Ub and then treated with NaCl (+34 mM) for 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Flag: 
HA: 
USP33: 23032
p97: 7415"
  },
  {
    "caption": "L Immunoprecipitation  analysis of Viperin ubiquitination in  HT1080 cells transfected with shCtrl or shp97 (1# or 2#) and then treated with IFNα (1,000 IU/ml, 12 hrs) immediately after addition of NaCl (+34 mM). Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "N Western blot analysis of  Myc-Viperin in HEK293T cells co-transfected with Myc-Viperin  and shCtrl or shp97, and then treated with additional NaCl (+34 mM) for 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Myc: 
Viperin: 91543
p97: 7415"
  },
  {
    "caption": "E, F Mass spectrometry analysis of acetylation of Flag-p97  (E) in RAW264.7 transfected with Flag-p97 and then treated with additional NaCl  (+34 mM) or control ddH2O (Ctrl) for 12 hrs. The intensity of p97-K663 site was shown in (F).",
    "ncbi_link": "Flag: 
p97: 269523"
  },
  {
    "caption": "H  Immunoprecipitation analysis of the interaction between  USP33  and Myc-p97 in  HEK293T  cells transfected with Myc-p97 (WT or K663R). Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Myc: 
p97: 269523"
  },
  {
    "caption": "L Western blot analysis of FH-USP33 levels in p97-KO  HEK293T cells co-transfected with Myc-p97 (WT or K663R) and Flag-USP33, and then treated with additional NaCl  (+34 mM) for 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Flag: 
Myc: 
USP33: 23032
p97: 7415
p97: 269523"
  },
  {
    "caption": "M Immunoprecipitation  analysis of  Viperin ubiquitination in  p97-KO 2fTGH cells co-transfected with Myc-p97 (WT or K663R), Flag-Viperin and HA-Ub as indicated, and then treated with additional NaCl (+34 mM) for 12 hrs. Data information: Data are representative of at least two biological replicates.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Viperin: 91543
p97: 7415
p97: 269523"
  },
  {
    "caption": "Ctrl or Trim21- deficient THP-1s were stimulated for 4 h with 1000 U/ml IFNα and TRIM21 expression measured by immunoblot.",
    "ncbi_link": "Trim21: 6737"
  },
  {
    "caption": "WT or TRIM21- deficient THP-1s were stimulated with AdV (50 000 pp/cell) and 20 μg/ml h9C12 or 20 mg/ml IVIg or with 200 ng/well HT-DNA or 10 μM Nigericin for 16h, and IL-1β measured in the supernatant by ELISA.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "WT or TRIM21- deficient THP-1s were stimulated with AdV (50 000 pp/cell) and 20 μg/ml h9C12 or 20 mg/ml IVIg or with 200 ng/well HT-DNA or 10 μM Nigericin for 16h, and TNF measured in the supernatant by ELISA.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "HMDM were stimulated as in (A), or with 10 ng/ml LPS for 3 h and NLRP3 mRNA expression measured by qPCR. Data shows average ± s.d. of 2 independent donors",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "TLR9 mRNA levels from PBMCs, CD19+ve B cells, CD14+ve monocytes or HMDM derived from CD14+ve monocytes were assessed by qPCR and copy number was determined relative to actin copy number (n = 5 mean ± s.e.m).",
    "ncbi_link": "actin: 
TLR9: 54106"
  },
  {
    "caption": "WT, NLRP3, ASC or Caspase-1 - deficient THP-1s were stimulated as in (A) and IL-1β in the supernatant measured by ELISA. Data is representative of two independent experiments.",
    "ncbi_link": "Caspase-1: 834
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "AIM2 mRNA levels from PBMCs, CD19+ve B cells, CD14+ve Monocytes or HMDM derived from CD14+ve monocytes. were assessed by qPCR and copy number was determined relative to Actin copy number (n = 5 mean ± s.e.m).",
    "ncbi_link": "Actin: 
AIM2: 9447"
  },
  {
    "caption": "THP-1s expressing either a control guide RNA or targeting cGAS and STING were generated and stimulated with 1000 U/ml IFNα for 4 h and protein levels assessed by western blot.",
    "ncbi_link": "cGAS: 115004
STING: 340061"
  },
  {
    "caption": "THP-1s deficient in cGAS and STING were stimulated with AdV (50 000 pp/cell) and 20 μg/ml h9C12, 200 ng/ well HT-DNA, 10 μM Nigericin or 10 ng/ml LPS for 16 h. Data shows combined data (mean ± s.e.m) of 3 experiments with absolute protein values (upper panel) or as % cytokine output of KO cells relative to Ctrl treated cells (lower panel), *P-value ≤ 0.05, ***P-value ≤ 0.001 unpaired, two-tailed t-test).",
    "ncbi_link": "cGAS: 115004
STING: 340061"
  },
  {
    "caption": "(A) Representative whole mount images of WT and Cep63T/T brains at P60. Scale bar = 0.2 cm. (B) Telencephalon area of WT and Cep63T/T brains. WT littermates N = 4, Cep63T/T N = 7; two-tailed Mann-Whitney t-test.",
    "ncbi_link": "Cep63: 28135"
  },
  {
    "caption": "(C) Representative whole mount images of WT and Sas4cKO brains at P14. Scale bar: 0.2 cm. (D) Telencephalon area of WT and Sas4cKO brains. WT littermates N = 8, Sas4cKO N = 7; two-tailed Mann-Whitney t-test. Black circles represent Nestin-Cre+ animals.",
    "ncbi_link": "Sas4: 219103
Cre: 2777477
Nestin: 18008"
  },
  {
    "caption": "(E) Representative images of E14.5 WT, Cep63T/T and Sas4cKO cortices stained with antibodies against α-Tubulin (green), γ-Tubulin (red) and DAPI (blue). Magenta arrows indicate dead cells; white and yellow arrows indicate cells with bipolar and monopolar spindles, respectively. Insets showing zoomed in view of 2 representative cells. Dashed lines showing the orientation of the cleavage plane relative to the ventricular surface. Scale bar = 25 μm. (F) Graph showing the percentage of bipolar, monopolar and multipolar cells at the ventricular surface of E14.5 cortices. WT n = 201 cells, N = 3 embryos; Cep63T/T n = 312 cells, N = 3 embryos; Sas4cKO n = 296 cells, N = 3 embryos; #, chi-square test with *, post-hoc analysis, comparisons are made to WT.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135"
  },
  {
    "caption": "(H) Ratio of mitotic (PH3+) to cycling (Ki67+) cells in E14.5 cortices. WT N = 5, Cep63T/T N = 3, Sas4cKO N = 3; two-tailed Mann-Whitney t-test.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135"
  },
  {
    "caption": "(J) Representative images from live-cell movies of Nuclear-mCherry+ WT, Cep63T/T and Sas4cKO NPCs. The timing of mitosis began at nuclear envelope breakdown (NEBD) and finished at nuclear envelope reformation. White arrows track the mitotic events of the mother cell from NEBD to the generation of daughter cells following cytokinesis. (K) Plot showing the duration of mitosis in WT, Cep63T/T and Sas4cKO NPCs. Triangles represent individual cells; triangles of the same color represent cells derived from the same embryo. Circles represent the average mitotic duration of cells from each embryo. WT n = 202 cells, N = 4 embryos; Cep63T/T n = 141 cells, N = 3 embryos; Sas4cKO n = 138 cells, N = 3 embryos; two-tailed Welch's t-test.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135"
  },
  {
    "caption": "(A-C) Graph showing the mitotic duration of NPCs and the fate of their progeny in primary cultures generated from E14.5 embryos. Each bar represents one cell; its height represents the amount of time the mother cell spent in mitosis; bar color represents the fate of the progeny. Dashed line is set at 30 mins. WT n = 330 cells, N = 4 embryos; Cep63T/T n = 260 cells, N = 3 embryos; Sas4cKO n = 223 cells, N = 3 embryos. (D-F) Percentage of proliferating, arrested and apoptotic progeny within each group of the indicated mitotic duration, calculated from data shown in A-C; groups with n < 20 cells were excluded from this quantification; #, chi-square test with *, post-hoc analysis, within each genotype, comparisons are made to the 0-30min group.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135"
  },
  {
    "caption": "(G) Genome-wide copy number plots of single cells sequenced from dissociated dorsolateral telencephalons of E14.5 embryos. Individual cells are represented in rows with copy number states indicated by colors; arrows on the zoomed in view (right) indicate aneuploid cells. WT n = 38 cells, N = 2 embryos; Cep63T/T n = 40 cells, N = 2 embryos; Sas4cKO n = 42 cells, N = 2 embryos. (H) Percentage of aneuploid cells from the single-cell sequencing data shown in G.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135"
  },
  {
    "caption": "(A) Representative whole mount images of WT, Sas4cKO, Sas4cKO;Trp53bp1-/-, Sas4cKO;Usp28cKO animals at P14. Arrows indicate the cerebellar hypoplasia resulting from the lack of primary cilia. Scale bar = 0.2 cm. (B) Telencephalon area of P14 brains of the indicated genotypes. WT littermates N = 8, Sas4cKO N = 7, Sas4cKO;Trp53bp1-/- N = 6, Sas4cKO;Usp28cKO N = 10, Sas4cKO;Trp53-/- N = 5; one-way ANOVA with post-hoc analysis. WT and Sas4cKO data are from Figure 1D and shown alongside for comparison. Black circles represent Nestin-Cre+ animals. (C) Cortical thickness of P14 brains of the indicated genotypes. WT littermates N = 4, Sas4cKO N = 4, Sas4cKO;Trp53bp1-/- N = 4, Sas4cKO;Usp28cKO N = 4, Sas4cKO;Trp53-/- N = 4; one-way ANOVA with post-hoc analysis. WT and Sas4cKO data are from Figure EV1D and shown alongside for comparison. Black circles represent Nestin-Cre+ animals.",
    "ncbi_link": "Sas4: 219103
Cre: 2777477
Nestin: 18008
Trp53: 22059
Trp53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(D) Representative whole mount images of WT, Cep63T/T, Cep63T/T;Trp53bp1-/-, Cep63T/T ;Usp28-/- animals at P60. Scale bar = 0.2 cm. (E) Telencephalon area of P60 brains of the indicated genotypes. WT littermates N = 4, Cep63T/T N = 7, Cep63T/T;Trp53bp1-/- N = 6, Cep63T/T;Usp28-/- N = 5; one-way ANOVA with post-hoc analysis. WT and Cep63T/T data are from Figure 1B and shown alongside for comparison. (F) Cortical thickness of P60 brains of the indicated genotypes. WT littermates N = 4, Cep63T/T N = 5, Cep63T/T;Trp53bp1-/- N = 3, Cep63T/T;Usp28-/- N = 3; one-way ANOVA with post-hoc analysis. WT and Cep63T/T data are from Figure EV1B and shown alongside for comparison.",
    "ncbi_link": "Cep63: 28135
Trp53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(G) Body weight of P7 animals of the indicated genotypes. WT littermates N=18, Cep63T/T N=16, Cep63T/T;Trp53bp1-/- N=2, Cep63T/T;Usp28-/- N=10; one-way ANOVA with post-hoc analysis.",
    "ncbi_link": "Cep63: 28135
Trp53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(H) Quantification of total number of cells within a 500 μm-width column of cortices at P60. WT littermates N = 4, Cep63T/T N = 4, Cep63T/T;Trp53bp1-/- N = 4, Cep63T/T;Usp28-/- N = 3; one-way ANOVA with post-hoc analysis .",
    "ncbi_link": "Cep63: 28135
Trp53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(I-J) Quantification of the number of cells in the (I) superficial layer (CUX1+) and (J) deep layer (CTIP2+) within a 500 μm-width column of P60 cortices. WT littermates N = 3, Cep63T/T N = 4, Cep63T/T;Trp53bp1-/- N = 4, Cep63T/T;Usp28-/- N = 3; one-way ANOVA with post-hoc analysis .",
    "ncbi_link": "Cep63: 28135
Trp53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(A) Cortices from E14.5 brains stained with antibodies against the radial glial cell marker PAX6 (yellow), intermediate progenitor marker TBR2 (red) and DAPI (blue). Scale bar = 50 μm. (B and C) Quantification of the number of (B) radial glial cells (PAX6+) and (C) intermediate progenitors (TBR2+) within a 250 μm-width column of E14.5 cortices. WT N=3, Cep63T/T N = 3, Cep63T/T;Usp28-/- N = 3, Sas4cKO N = 3, Sas4cKO;Usp28cKO N = 3; one-way ANOVA with post-hoc analysis.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135
Usp28: 235323"
  },
  {
    "caption": "(D) Cortices from E14.5 embryos stained with antibodies against Cleaved-Caspase 3 (CC3, white), TP53 (red) and DAPI. Scale bar = 50 μm. (E and F) Quantification of the number of CC3+ apoptotic cells (E) and cells with TP53 activation (F) within a 250 μm-width column of E14.5 cortices. WT N = 5, Cep63T/T N = 3, Cep63T/T;Usp28-/- N = 3, Sas4cKO N = 4, Sas4cKO;Usp28cKO N = 4; one-way ANOVA with post-hoc analysis.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135
Usp28: 235323"
  },
  {
    "caption": "(B) Percentage of bipolar, monopolar and multipolar cells at the ventricular surface of E14.5 cortices. WT n = 201 cells, N = 3 embryos; Cep63T/T;Usp28-/- n = 205 cells, N = 3 embryos; Sas4cKO;Usp28cKO n = 308 cells, N = 3 embryos; #, chi-square test with *, post-hoc analysis, comparisons are made to WT. WT data are from Figure 1F and shown alongside for comparison.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135
Usp28: 235323"
  },
  {
    "caption": "(C) Ratio of mitotic (PH3+) to cycling (Ki67+) cells in E14.5 cortices. WT N = 5, Cep63T/T;Usp28-/- N = 3, Sas4cKO;Usp28cKO N = 3; two-tailed Mann-Whitney t-test. 3 WT data points are from Figure 1H and shown alongside for comparison.",
    "ncbi_link": "Sas4: 219103
Cep63: 28135
Usp28: 235323"
  },
  {
    "caption": "(D) Representative images from live-cell movies of Nuclear-mCherry+ WT, Sas4cKO and Sas4cKO;Usp28cKO NPCs. White arrows showing the nuclei of daughter cells following cytokinesis. (E) Plot showing quantification of mitotic duration of WT, Sas4cKO and Sas4cKO;Usp28cKO NPCs. Triangles represent individual cells; triangles of the same color represent cells derived from the same embryo. Circles represent the average mitotic duration of cells from each embryo. WT n = 202 cells, N = 4 embryos; Sas4cKO n = 138 cells, N = 3 embryos; Sas4cKO;Usp28cKO n = 191 cells, N = 3 embryos; two-tailed Welch's t-test. WT and Sas4cKO data are from Figure 1K and shown alongside for comparison. (F) Graph showing the mitotic duration of NPCs and the fate of their progeny in primary cultures generated from Sas4cKO;Usp28cKO E14.5 embryos. Each bar represents one cell; its height represents the amount of time the mother cell spent in mitosis; bar color represents the fate of the progeny. Dashed line is set at 30 min. Sas4cKO;Usp28cKO n = 271 cells, N = 3 embryos. (G) Percentage of proliferating, arrested and apoptotic progeny within each group of the indicated mitotic duration, calculated from data shown in F; #, chi-square test with *, post-hoc analysis, comparisons are made to the 0-30min group.",
    "ncbi_link": "Sas4: 219103
Usp28: 235323"
  },
  {
    "caption": "Graph showing the mitotic duration of NPCs and the fate of their progeny in primary cultures generated from Sas4cKO E14.5 embryos. Each bar represents one cell; its height represents the amount of time the mother cell spent in mitosis; bar color represents the fate of the progeny. Dashed line is set at 30 min. (H and I) Data from Figures 2C and 2F shown alongside for comparison with F and G.",
    "ncbi_link": "Sas4: 219103"
  },
  {
    "caption": "(a) WT and Smc5cKO cortices at E14.5 stained with antibodies against Centrin (green), γ-Tubulin (red) and DAPI (blue). Insets showing zoomed in view of 2 representative cells. Scale bar: 25 μm. (B and C) Quantification of the number of (B) Centrin foci and (C) γ-Tubulin foci in mitotic cells in the VZ of E14.5 cortices. WT n = 175 cells, N = 4 embryos; Smc5cKO n = 134 cells, N = 3 embryos. #, chi-square test. WT data are from Figures EV1F and EV1G and shown alongside for comparison.",
    "ncbi_link": "Smc5: 226026"
  },
  {
    "caption": "(E) Ratio of mitotic (PH3+) to cycling (Ki67+) cells in E14.5 cortices. WT N = 5, Smc5cKO N = 5; two-tailed Mann-Whitney t-test. WT data are from Figure 1H and shown alongside for comparison.",
    "ncbi_link": "Smc5: 226026"
  },
  {
    "caption": "(F Quantification of the number of (F) apoptotic cells (CC3+) within a 250 μm-width column of E14.5 cortices. WT N = 5, Smc5cKO N = 4; two-tailed Mann-Whitney t-test. WT data are from Figures 4E and 4G and shown alongside for comparison.",
    "ncbi_link": "Smc5: 226026"
  },
  {
    "caption": "G) Quantification of the number of (G) cells with TP53 activation within a 250 μm-width column of E14.5 cortices. WT N = 5, Smc5cKO N = 4; two-tailed Mann-Whitney t-test. WT data are from Figures 4E and 4G and shown alongside for comparison.",
    "ncbi_link": "Smc5: 226026"
  },
  {
    "caption": "(H) Representative whole mount images of WT, Smc5cKO, Smc5cKO;Usp28cKO, Smc5cKO;Trp53-/- brains at P21. Scale bar = 0.2 cm. (I) Telencephalon area of P21 brains of the indicated genotypes. WT littermates N = 6, Smc5cKO N = 5, Smc5cKO;Usp28cKO N = 4, Smc5cKO;Trp53-/- N = 5; one-way ANOVA with post-hoc analysis.",
    "ncbi_link": "Smc5: 226026
Trp53: 22059
Usp28: 235323"
  },
  {
    "caption": "(b) An increase in ROCK1-mediated phosphorylation of MYPT1 upon starvation. HeLa and EJ cells were starved in HBSS for indicated time points and endogenous ROCK1 was immunoprecipitated. An in vitro kinase assay was performed using MYPT1 as substrate and immune-complexed ROCK1. Proteins were resolved and visualized with Coomassie staining (top), western blot analysis (middle) and autoradiography (bottom). Inputs were examined for ROCK1 and β-actin.",
    "ncbi_link": "MYPT1: 4659"
  },
  {
    "caption": "(e) ROCK1 activity is not dependent on Beclin1. siControl (siCont.) and siBeclin1 knockdown cells were incubated in starvation media (HBSS) for indicated time. Resulting cell extracts were used to confirm Beclin1 knockdown and ROCK1 expression (left panel). Cell extracts from the same experiment were used for enzyme-linked immunosorbent assay measuring ROCK activity (right panel). Graph represents mean±s.d. of duplicate samples read at the same time (Student's t-test; NS, not significant).",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(a) The effect of ROCK1 depletion on autophagy marker, LC3II. MEF ROCK1flox/flox cells were generated and treated with Con or Ad-Cre for 72 h. Cells were then incubated in nutrient-rich (+Glucose) or HBSS media for 2 h. Cell extracts were resolved by SDS-PAGE and ROCK1 KO was confirmed by western blotting (left panel). The same blot was used for LC3 and β-actin expression. Cells from the same experiment were fixed with chilled acetone and immunofluroscence was performed against endogenous LC3 (red). Blue represents nuclear DAPI staining. Scale bar, 20 μm.",
    "ncbi_link": "Cre: 
ROCK1: 19877"
  },
  {
    "caption": "(b) EJ cells (left) with a stable knockdown using shCont. or shROCK1#1 were incubated in control (+glucose) or nutrient-free (HBSS) medium (−glucose) for 24 h and lysed. Lysates were subjected to western blotting with antibodies indicated. HeLa cells (right) with a transient knockdown using siCont. and siROCK1#2 for 30 h were further incubated in control or HBSS media for 8 h. Whole cell extracts were prepared, resolved by SDS-PAGE and analysed for ROCK1, LC3 and β-actin. Relative ratios of LC3II/LC3I are shown.",
    "ncbi_link": "ROCK1: 6093"
  },
  {
    "caption": "(e) Transmission electron micrographs of EJ cells with stable shCont. or shROCK1#1 knockdown, cultured in control or HBSS medium for 16 h. Arrow bars indicate autophagic vacuoles. Scale bar, 500 nm.",
    "ncbi_link": "ROCK1: 6093"
  },
  {
    "caption": "(c) Identification of ROCK1-mediated phosphorylation domains in Beclin1. The indicated Flag-Beclin1 fragments were purified from HeLa cells and used as substrates for in vitro ROCK1 kinase assay. 32P-autoradiogram (centre) analysed phosphorylation and western blotting (WB; right) determined protein levels. Schematic representation of Beclin1 domain structure and deletion constructs are shown (left).",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(d) Identification of the phosphorylation site on Beclin1. Representation of point mutations in the different domains of Beclin1 are shown (left). In vitro kinase assay using Flag-Beclin1 WT and mutants (T38A and T119A), immunoprecipitated from transfected HeLa cells, as substrate and recombinant ROCK1 was performed. Phosphorylation was detected by 32P-autoradiogram, and Flag-Beclin1 levels were examined by WB.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(e) Flag-Beclin1 Wt or T119A transfected HeLa cells were incubated in glucose-rich or nutrient-free (HBSS) media, in the presence or absence of ROCK1 inhibitor Y27632. Total cell extracts were used for IP using Flag agarose. Eluted protein was analysed by WB against phospho-T119 (Beclin) antibody and Beclin1. Input for Beclin1 was run on 7.5% gel and immunoblotted.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(a) Inhibiting ROCK1 activity increases the association between Beclin1 and Bcl-2. HeLa cells, untreated or treated with 10 μM Y27632 (top panel), were cultured in control or glucose-free (4 h) medium, lysed and cell extracts prepared. Endogenous Bcl-2 was immunoprecipitated with cross-linked Bcl-2 agarose and resulting eluted immune complexes were resolved by SDS-PAGE and blotted against indicated antibodies. EJ shCont. and shROCK1#1 cells (bottom panel) were grown in control or starvation media for 4 h and Bcl-2 IP was performed as above. Inputs were rerun to confirm ROCK1 knockdown.",
    "ncbi_link": "ROCK1: 6093"
  },
  {
    "caption": "(b) HeLa cells were transfected with full-length constructs of Flag-Beclin WT, Flag-Beclin T119A or Flag-Beclin T119E. Flag-Beclin WT cells were then treated with Y27632 for 8 h. Post transfection and treatment with Y27632, cells were starved in HBSS medium for 4 h, after which cells were collected and whole cell lysates prepared. IP with Flag-agarose was performed for 2 h and proteins bound to beads were eluted and used for western blotting.",
    "ncbi_link": "Beclin: 8678"
  },
  {
    "caption": "(c) Flag-Beclin1 Wt or T119A transfected HeLa cells were incubated in glucose-rich or nutrient-free (HBSS) media, in the presence or absence of ROCK1 inhibitor Y27632. Total cell extracts were used for IP using Flag agarose. Eluted protein was analysed by western blotting against Bcl-2 and Beclin1. Inputs and IP were run on separate gels and same exposure is shown.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(d) HeLa cells with a transient knockdown using siCont. and siBeclin1-3′-untranslated region for 30 h were further left untreated or treated with 10 μM Y27632. Cells were then incubated in control or HBSS media for 8 h. Whole cell extracts were prepared, resolved by SDS-PAGE and were analysed for Beclin1, LC3 and β-actin.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(e) Endogenous LC3 staining in WT- or T119A-Beclin1-transfected cells. HeLa cells transfected with Flag-Beclin WT (±Y27632) and T119A were cultured in HBSS media for 6 h, fixed with cold acetone and endogenous LC3 immunofluorescence was performed. Representative images are shown; scale bar, 20 μm. Arrows indicate punctate LC3 staining. Graph represents mean±s.d., n=25, LC3 puncta/cell.",
    "ncbi_link": "Beclin: 8678
Beclin1: 8678"
  },
  {
    "caption": "(b) PCR assay using tail genomic DNA from three different genotypes, separated on 0.7% agarose gel (top). Western blot analysis of ROCK1 expression in the heart tissue from three different genotypes using anti-ROCK1 antibody (bottom). β-Actin was used for protein loading control in each lane.",
    "ncbi_link": "ROCK1: 19877"
  },
  {
    "caption": "(d) ROCK1-deficient hearts or control hearts from animals fed or starved for 16 h were subjected to electron microscopy to identify autophagosome structures. Arrows indicate autophagic vacuoles. Scale bar, 500 nm.",
    "ncbi_link": "ROCK1: 19877"
  },
  {
    "caption": "(e) Hearts from fed and starved ROCK1 WT and KO mice were sectioned, fixed in acetone and immunofluorescence assay was performed against endogenous LC3. Data are representative of two independent experiments from each genotype. Scale bar, 50 μm.",
    "ncbi_link": "ROCK1: 19877"
  },
  {
    "caption": "Heatmap showing protein (SASP, from http://www.saspatlas.com/; log fold ratio)and  gene expression levels (log2FC) of IMR90 SASP-related genes embedded in high-HMGB1 (red) TADs like those in panel C. **: genes bound by HMGB1 in ChIP-seq  data are more than expected by chance; P>0.001, hypergeometric test.",
    "ncbi_link": "HMGB1: 3146"
  },
  {
    "caption": "Immunofluorescence  (top), western blot (middle) and RT-qPCR analyses (bottom; mean fold-change ±S.D. from two biological replicates) confirm HMGB1 knockdown in  IMR90.",
    "ncbi_link": "HMGB1: 3146"
  },
  {
    "caption": "Representative images of IMR90 overexpressing HMGB1-GFP, immunostained for  p21 and CTCF, and  counterstained  with DAPI. IMR90 transfected with empty vectors provide a control. Bar: 5 μm.",
    "ncbi_link": "GFP: 
HMGB1: 3146"
  },
  {
    "caption": "Genome browser views showing HMGB1 sCLIP data (black) along the ASH1L, CCNL2 and TET2  loci; input tracks (grey) provide background levels. *: significantly-enriched peaks. The consensus motif for HMGB1 binding  on RNA is also shown (bottom right).",
    "ncbi_link": "ASH1L: 55870
CCNL2: 81669
TET2: 54790"
  },
  {
    "caption": "Bar graphs showing mean fold-change of selected mRNAs (over ±S.D. from two biological replicates) from ILF3- (purple), RBMX- (white) or  PNN-knockdown experiments (blue) in proliferating IMR90. *: significantly different to siRNA controls; P<0.01, unpaired two-tailed Student's t-test. Dashed line indicates no change in expression.",
    "ncbi_link": "ILF3: 3609
PNN: 5411
RBMX: 27316"
  },
  {
    "caption": "(A) Huh7.5 cells were transfected with the negative control siRNA (NC) or the Rubicon (Rb) siRNA for 48 hours and then infected with 1 m.o.i. of HCV. Western-blot analysis of cell lysates at different time points after HCV infection. Actin served as the loading control.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(B) Huh7.5 cells were transfected with the negative control siRNA (NC) or the Rubicon (Rb) siRNA for 48 hours and then infected with 1 m.o.i. of HCV. Real-time RT-PCR analysis of HCV RNA at 24 and 48 hours post-infection. *, p < 0.05. siNC, negative control siRNA; siRb, Rubicon siRNA.",
    "ncbi_link": "HCV RNA: 
Rubicon: 9711"
  },
  {
    "caption": "Huh7.5 cells were transfected with the negative control siRNA (NC) or the Rubicon (Rb) siRNA for 48 hours and then infected with 1 m.o.i. of HCV. (C) Fluorescence imaging of RFP and GFP puncta in cells transfected with the control siRNA (top two panels) or the Rubicon siRNA (bottom two panels). Cells were fixed at 24 and 48 hours after HCV infection for the analysis. Boxed areas in merged images are enlarged and shown to the right. (D) Percentages of RFP puncta that were also positive for GFP in Huh7.5 cells treated with either the control siRNA or the Rubicon siRNA. The results represent the average of >50 cells.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(A) Huh7.5 cells were transfected with the control vector or the Flag-tagged Rubicon expression plasmid for 24 hours followed by infection with HCV. Western-blot analysis of cell lysates at different time points after infection. Mock-infected cells were lysed at 48 hours post-transfection.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(B) Huh7.5 cells were transfected with the control vector or the Flag-tagged Rubicon expression plasmid for 24 hours followed by infection with HCV. Real-time RT-PCR analysis of HCV RNA at 24 and 48 hours post-infection. *, p < 0.05.",
    "ncbi_link": "HCV RNA: 
Rubicon: 9711"
  },
  {
    "caption": "Huh7.5 cells were transfected with the control vector or the Flag-tagged Rubicon expression plasmid for 24 hours followed by infection with HCV. (C) RFP and GFP puncta in cells with the over-expression of Rubicon at different time points after HCV infection. Merged images are shown to the right. (D) Percentages of RFP puncta that were also positive for GFP in Huh7.5 cells transfected with either the control vector or the Rubicon expression plasmid. The results represent the average of >50 cells.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "
",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "Huh7.5 cells were transfected with the control vector or the Flag-tagged UVRAG expression plasmid for 24 hours followed by infection with HCV. (B) Real-time RT-PCR analysis of HCV RNA at 24 and 48 hours post-infection. *, p < 0.05.",
    "ncbi_link": "HCV RNA: 
UVRAG: 7405"
  },
  {
    "caption": "Huh7.5 cells were transfected with the control vector or the Flag-tagged UVRAG expression plasmid for 24 hours followed by infection with HCV. (C) RFP and GFP puncta in cells with the over-expression of UVRAG at different time points after HCV infection. Merged images are shown to the right. (D) Percentages of RFP puncta that were also positive for GFP in Huh7.5 cells transfected with either the control vector or the UVRAG expression plasmid. The results represent the average of >50 cells.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "Cells transfected with the control siRNA (siNC), the Rubicon siRNA (siRb), the Rubicon expression plasmid (pRubicon) or the UVRAG expression plasmid (pUVRAG) were infected with HCV (m.o.i. = 1). The incubation media were harvested at 24 and 48 hours post-infection and used to infect naïve Huh7.5 cells. Cells were either fixed and stained for the HCVcore protein for the determination of viral titers (A)",
    "ncbi_link": "Rubicon: 9711
UVRAG: 7405"
  },
  {
    "caption": "Cells transfected with the control siRNA (siNC), the Rubicon siRNA (siRb), the Rubicon expression plasmid (pRubicon) or the UVRAG expression plasmid (pUVRAG) were infected with HCV (m.o.i. = 1). The incubation media were harvested at 24 and 48 hours post-infection and used to infect naïve Huh7.5 cells. Cells were lysed for Western-blot analysis of the HCVcore protein (B) two days after infection. Actin served as the loading control in (B).",
    "ncbi_link": "Rubicon: 9711
UVRAG: 7405"
  },
  {
    "caption": "(A) Increase of Rubicon, UVRAG, p62 and LC3-II in HCV subgenomic RNA replicon cells. Actin served as the loading control. Numbers under Rubicon and UVRAG indicate the protein levels of Rubicon and UVRAG in replicon cells relative to their levels in control Huh7 cells.",
    "ncbi_link": "HCV subgenomic RNA: "
  },
  {
    "caption": "(C) Colocalization analysis of GFP-LC3 puncta and lysosomes. Stable Huh7 cells that expressed GFP-LC3 were nutrient-starved for 2 hours and stained with Lysotracker-red for lysosomes. The HCV replicon cells were also stained with Lysotracker-red for comparison. (D) Colocalization efficiency of GFP puncta with Lysotracker-red shown in (C). The results represent the average of >30 cells.",
    "ncbi_link": "HCV: "
  },
  {
    "caption": "(E) Effect of Rubicon knockdown on parental Huh7 cells and HCV replicon cells. Huh7 cells and HCV replicon cells were treated with the control siRNA or the Rubicon siRNA for two days. Cells were then lysed for Western-blot analysis.",
    "ncbi_link": "HCV: "
  },
  {
    "caption": "(F) Relative HCV RNA levels as measured by real-time RT-PCR. HCV replicon cells treated with either the control siRNA or the Rubicon siRNA for two days were lysed for quantification of HCV RNA by real-time RT-PCR.",
    "ncbi_link": "HCV: 
HCV RNA: 
Rubicon: 9711"
  },
  {
    "caption": "(G) Effect of UVRAG overexpression on HCV replicon cells. HCV replicon cells were transfected with the control vector or flag-UVRAG plasmid for two days. Cells were then lysed for Western-blot analysis.",
    "ncbi_link": "HCV: 
UVRAG: 7405"
  },
  {
    "caption": "(H) Relative HCV RNA levels as measured by real-time RT-PCR. HCV replicon cells transfected with either the control vector or the flag-UVRAG plasmid for two days were lysed for quantification of HCV RNA by real-time RT-PCR. In (F) and (H), *, p<0.05.",
    "ncbi_link": "HCV: 
HCV RNA: 
UVRAG: 7405"
  },
  {
    "caption": "(a-c) Knockdown of pro-autophagic proteins restores Δ133p53α expression. MRC-5 fibroblasts at late-passage (PDLs 51) were transfected with three independent siRNA oligonucleotides (lanes 1-3) against ATG5 (a), ATG7 (b) and Beclin-1 (c), along with their control siRNA (lane C), for 4 days. Knockdown of ATG5 was confirmed by the loss of ATG5-ATG12 conjugate (detected by anti-ATG5 antibody). Knockdown of the other two proteins was confirmed using the corresponding antibodies. Δ133p53α, full-length p53 and LC3B (LC3-I and LC3-II) were examined in all samples. The relative expression levels of Δ133p53α and full-length p53 (normalized with β-actin) are shown below the images.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
Beclin-1: 8678"
  },
  {
    "caption": "(d) Knockdown of pro-autophagic proteins and treatment with bafilomycin A1 show similar effects on Δ133p53α and p62/SQSTM1. MRC-5 fibroblasts at late-passage (PDLs 51) were transfected with control siRNA (c), ATG5 siRNA (A5, no. 1 in a), ATG7 siRNA (A7, no. 1 in b) and Beclin-1 siRNA (B1, no. 2 in c) as in a-c, untreated (−) or treated with bafilomycin A1 (+, 100 nM for 4 h), and examined in immunoblots for indicated proteins. The relative expression levels of Δ133p53α and p62/SQSTM1 (normalized with β-actin) are shown below the images.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
Beclin-1: 8678"
  },
  {
    "caption": "(b) STUB1 mRNA is downregulated at replicative senescence. The same set of cells as in a were examined by qRT-PCR. Data were from triplicate experiments (mean±s.d.). *P0.01; **P0.001 (Student's t-test).",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "(c) Knockdown of STUB1 represses Δ133p53α. MRC-5 fibroblasts (30 PDLs) were transfected with two siRNAs against STUB1 (no. 1 and no. 2) and control siRNA. At 4 days after transfection, immunoblots were performed using anti-STUB1, anti-Δ133p53α, DO-1 (detecting full-length p53), CM1 (detecting both Δ133p53α and full-length p53), anti-p62/SQSTM1 and anti-β-actin antibodies.",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "(d) STUB1 knockdown inhibits cell proliferation. MRC-5 fibroblasts (30 PDLs) were seeded on six-well plates on day 0 (4 × 104 cells per well in 6-well plate; nine wells for each siRNA). Cells were counted on days 1, 4 and 7 (three wells each; mean±s.d.), while siRNA transfection was performed on days 1 and 4. *P0.01 (Student's t-test).",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "(e) STUB1 knockdown induces cellular senescence. The siRNA transfection was performed as in c and repeated 4 days later, followed by incubation for 3 days and SA-β-Gal staining. Percentages of SA-β-Gal-positive cells were from triplicate experiments (mean±s.d.). **P0.001 (Student's t-test).",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "(f,g) STUB1 knockdown upregulates p21WAF1 and IL-8. The same set of cells as in e were examined in qRT-PCR for p21WAF1 mRNA (f) and IL-8 mRNA (g). Data were from triplicate experiments (mean±s.d.). **P0.001 (Student's t-test).",
    "ncbi_link": "p21WAF1: 1026
IL-8: 3576
STUB1: 10273"
  },
  {
    "caption": "(h) Δ133p53α rescues STUB1 knockdown-induced senescence. MRC-5 fibroblasts were transfected with STUB1 siRNA (no. 1) as in e. At the next day after the second transfection (on day 5), the cells were transduced with a lentiviral vector driving Δ133p53α or its vector control. At 5 days after the lentiviral transduction, the cells were stained for SA-β-Gal activity. Representative pictures (left) and quantitative data (right) are shown. Percentages of SA-β-Gal-positive cells were from triplicate experiments (mean±s.d.). **P0.001 (Student's t-test).",
    "ncbi_link": "STUB1: 10273
p53: 7157"
  },
  {
    "caption": "(a) STUB1 knockdown-induced repression of Δ133p53α is abrogated by bafilomycin A1 treatment. The siRNA transfection in MRC-5 fibroblasts was performed as in Fig. 3e. At 7 days after the initial transfection, the cells were untreated, treated with bafilomycin A1 (100 nM for 4 h) or treated with MG-132 (15 μM for 4 h), and examined in immunoblots as indicated. The results of Δ133p53α, full-length p53 and p62/SQSTM1 in untreated cells replicate those shown in Fig. 3c. The inhibition of autophagy by bafilomycin A1 was confirmed by increased levels of p62/SQSTM1 and LC3B. The inhibition of proteasomal degradation by MG-132 was confirmed by increased full-length p53.",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "(b) STUB1 knockdown-induced repression of Δ133p53α is abrogated by knockdown of pro-autophagic proteins. MRC-5 fibroblasts (PDLs 30) were transfected for 4 days with control siRNA (−) or STUB1 siRNA (no. 1, +), in combination with control siRNA (c), p62/SQSTM1 siRNA (62), ATG5 siRNA (A5, no. 1 in Fig. 2a), ATG7 siRNA (A7, no. 1 in Fig. 2b) or Beclin-1 siRNA (B1, no. 2 in Fig. 2c), and examined in immunoblots for indicated proteins.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
Beclin-1: 8678
STUB1: 10273"
  },
  {
    "caption": "(a) Δ133p53α protein is polyubiquitinated. FLAG-tagged versions of wild-type Δ133p53α (wt) and mutant Δ133p53α (mut; from c below), along with vector control (−), were retrovirally transduced into MRC-5 fibroblasts. The wild-type Δ133p53α-expressing cells had a pair of STUB1 siRNA-transfected (+, siRNA no. 1 for 4 days) and untransfected (−) counterparts. These cells were maintained for 8 h under amino acid- and serum-starved conditions with bafilomycin A1 (100 nM). Protein lysates were used either in IP with anti-ubiquitin (Ub) antibody, followed by IB with anti-FLAG antibody (top), or directly in IB for FLAG-Δ133p53α, STUB1 and β-actin (lower three panels). Smear signals indicate polyubiquitinated FLAG-Δ133p53α protein (Poly-Ub). Asterisk indicates a nonspecific band in negative control. These experimental conditions resulted in similar amounts of FLAG-Δ133p53α in the presence and absence of STUB1 knockdown, allowing quantitative analysis of ubiquitination. The relative densitometric values of wild-type FLAG-Δ133p53α polyubiquitination in the presence and absence of STUB1 knockdown (normalized with total FLAG-Δ133p53α) are shown. (",
    "ncbi_link": "STUB1: 10273
p53: 7157"
  },
  {
    "caption": "(b) Δ133p53α is ubiquitinated at the C-terminal lysine residues. MRC-5 fibroblasts expressing wild-type FLAG-Δ133p53α in the absence of STUB1 knockdown were used in IP with anti-FLAG antibody, and the resulting immunoprecipitates were analysed using mass spectrometry. Representative MS/MS spectrum of an [M+3H]3+ peptide from FLAG-Δ133p53α shows sites of ubiquitin modification. The peptide sequence for the spectrum is shown, with the sites of modification marked as asterisks: amino-acid positions 248 and 249, which correspond to positions 381 and 382 in full-length p53. The same peptide was also observed in the unmodified state.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(d) Mutation of the ubiquitination sites renders Δ133p53α resistant to degradation. The same three cells as in a were cultured under amino-acid- and serum-starved conditions for 8 h (without bafilomycin A1), transfected with STUB1 siRNA (no. 1 for 4 days) or untreated, and examined in IBs for FLAG-Δ133p53α, STUB1, p62/SQSTM1 and β-actin. The effect of starvation was confirmed by decreased p62/SQSTM1 in each cell. The upregulation of p62/SQSTM1 by wild-type and mutant FLAG-Δ133p53α is likely associated with enhanced cell proliferation by Δ133p53α overexpression.",
    "ncbi_link": "STUB1: 10273
p53: 7157"
  },
  {
    "caption": "(b) Knockdown of p62/SQSTM1 stabilizes endogenous Δ133p53α. MRC-5 fibroblasts at late passage (PDLs 51) were transfected with p62/SQSTM1 siRNA (p62) or control siRNA (C) for 3 days, and examined in immunoblots for Δ133p53α and p62/SQSTM1 expression. The relative expression levels of Δ133p53α (normalized with β-actin) are shown.",
    "ncbi_link": "p62: 8878
SQSTM1: 8878"
  },
  {
    "caption": "a, Northern blot analysis of lamp-2 expression. Total RNA was hybridized using a lamp-2 cDNA2 probe and a murine glyceraldehyde-3-phosphate dehydrogenase probe.",
    "ncbi_link": "glyceraldehyde-3-phosphate dehydrogenase: 14433
lamp-2: 16784"
  },
  {
    "caption": "b, Western blot analysis of LAMP-2 expression. In control liver and kidney extracts the glycosylated LAMP-2 molecules were detected. In LAMP-2-/- tissues no LAMP-2 product was found.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "c, Increased mortality in LAMP-2 deficient outbred (C57B6/Jx129SV) mice. Forty-two control (closed circles) and LAMP-2-deficient mice (open circles) were monitored over 300 days.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "d, Loss of weight in early dying (n = 7 males) and surviving LAMP-2-deficient mice (n = 11 males) in comparison with control mice ( n = 12 males) monitored for 60 days after birth.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "a, Ultrastructure of autophagic vacuoles (arrowheads) in pancreatic acinar gland cells from a 6.5-month-old LAMP-2-deficient mouse.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "b, Autophagic vacuoles containing glycogen (g), cytosol and cellular constituents in a hepatocyte of an 8-day-old LAMP-2-/- mouse. m, mitochrondria; bc, bile canaliculus. c, Accumulation of numerous early autophagic vacuoles in cultured LAMP-2-/- hepatocytes. Arrow, large late autophagic vacuole containing partially degraded material. Insert, magnification of the region indicated by an asterisk with typical early autophagic vacuoles containing undigested cellular constituents. Scale bars: a, 3.5 µm; b, 0.2 µm; c, 1.3 µm; insert, 0.9 µm.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "c, Typical original twitch recordings of developed force of heart muscles from control (thin line) and LAMP-2-deficient (thick line) mice. d, Average values of developed force. Preparations of LAMP-2 deficient mice had a significantly lower baseline developed force at a stimulation frequency of 4 Hz and 10 Hz; P  0.01.",
    "ncbi_link": "LAMP-2: 16784"
  },
  {
    "caption": "Immunohistochemistry of APOE (red) and IBA-1 (green) on a section (A, blue Hoechst) and the subretinal side of a retinal flatmount (B and C) from a 12-month-old Cx3cr1GFP/GFP mouse (representative of 3 independent experiments, experiments omitting the primary antibody immunostaining served as negative controls). ONL: outer nuclear layer; RPE: retinal pigment epithelium.",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Quantitative RT-PCR of ApoEmRNA normalized with S26mRNA of C57BL/6J and Cx3cr1GFP/GFP monocytes cultured for 24 h in contact with POS of an overlaying retinal explant (n = 4/group per experiment; Mann-Whitney U-test, *P = 0.0286, the experiment was repeated twice with similar results).Quantitative RT-PCR of ApoEmRNA normalized with S26mRNA of C57BL/6J and Cx3cr1GFP/GFP FACS-sorted microglial cells, freshly extracted from adult brain (n = 4-5/group; Mann-Whitney U-test, C57BL/6J versus Cx3cr1GFP/GFP *P = 0.0159).Quantitative RT-PCR of ApoEmRNA normalized with S26mRNA of C57BL/6J and Cx3cr1GFP/GFP peritoneal macrophages cultured for 24 h with CX3CL1. (n = 4/group per experiment; Mann-Whitney U-test, *P = 0.0286. The experiment was repeated twice with similar results).",
    "ncbi_link": "S26: 
ApoE: 11816
Cx3cr1: 13051"
  },
  {
    "caption": "APOE Western blot analysis of equivalent amounts of supernatant protein from CX3CL1-exposed C57BL/6J and Cx3cr1GFP/GFP peritoneal macrophages at 24 h. Soluble Mer receptor tyrosine kinase that is released constitutively from cultured macrophages served as a loading control. The experiment was repeated twice with similar results.",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "12-month-old IBA-1 stained RPE flatmounts of Cx3cr1GFP/GFP (H) and Cx3cr1GFP/GFPApoE−/− (I) mice.Quantification of subretinal IBA-1+ mononuclear phagocytes in 2-month-old (left) and 12-month-old (right) mice of the indicated strains (n = 9-20/group ANOVA/Dunnett test at 12 months: Cx3cr1GFP/GFP versus any other group *P < 0.0001; Mann-Whitney U-test at 12 months of Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/− *P < 0.0001).",
    "ncbi_link": "ApoE: 11816
Cx3cr1: 13051"
  },
  {
    "caption": "Quantification of subretinal IBA-1+ mononuclear phagocytes after 4 days of light challenge of 2-month-old mice of the indicated strains (n = 10-25/group ANOVA/Dunnett test: Cx3cr1GFP/GFP versus any other group *P < 0.0001; Mann-Whitney U-test of Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/− *P < 0.0001).",
    "ncbi_link": "ApoE: 11816
Cx3cr1: 13051"
  },
  {
    "caption": "IBA-1- (green) and CD102- (red) stained RPE flatmounts 7 days after laser injury of 2-month-old Cx3cr1GFP/GFP (E) and Cx3cr1GFP/GFPApoE−/− (F) mice.Quantification of subretinal IBA-1+mononuclear phagocytes on the RPE counted on the RPE at a distance of 0-500 μm to CD102+CNV 7 days after the laser injury of 2-month-old mice of the indicated strains (n = 8-10 eyes/group ANOVA/Dunnett test: Cx3cr1GFP/GFP versus any other group *P < 0.0001; Mann-Whitney U-test of Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/− *P < 0.0001).",
    "ncbi_link": "ApoE: 11816
Cx3cr1: 13051"
  },
  {
    "caption": "Representative image of a RPE flatmount 12 h after the subretinal injection (red marking) of 4 μl PBS with 12,000 CFSE-stained thioglycollate-elicited peritoneal cells that contain 70% macrophages (inset close-up view).Quantifications of CFSE+F4/80+ macrophages at different time points after subretinal injections of C57BL/6J and Cx3cr1GFP/GFP CFSE+ macrophages (n = 5/per group (12 h) and n = 6/per group thereafter; Mann-Whitney U-test, C57BL/6J versus Cx3cr1GFP/GFP: 1 day n = 20/group *P < 0.0001; 2 day n = 6/group *P = 0.0317).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Representative cytometry images of SSC-A/CFSE and CD11b/F4/80 gated analysis of eye cell suspensions prepared 24 h after the injection of Cx3cr1GFP/GFP CFSE+ macrophages and cytometric quantification of eye cell suspensions at 24 h after the injection of C57BL/6J and Cx3cr1GFP/GFP macrophages into C57BL/6J (n = 16-20/group; Mann-Whitney U-test, *P = 0.0024).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Quantification of subretinal CFSE+ cells on RPE and retinal flatmounts 24 h after subretinal injections of CFSE+ magnetic-bead-sorted bone marrow-derived monocytes (Mo) from C57BL/6J and Cx3cr1GFP/GFPmice into C57BL/6Jmice (n = 8-12/group; Mann-Whitney U-test, *P = 0.0006).Quantification of subretinal CFSE+ cells on RPE and retinal flatmounts 24 h after subretinal injections of CFSE+CD11bFACS-sorted brainmicroglial cells from C57BL/6J and Cx3cr1GFP/GFPmice into C57BL/6Jmice (n = 9-12/group; Mann-Whitney U-test, *P = 0.0087).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Quantification of subretinal CFSE+F4/80+macrophages on RPE and retinal flatmounts 24 h after subretinal injections of CFSE+macrophages from C57BL/6J, Cx3cr1GFP/GFP, Cx3cr1GFP/GFPApoE−/−, and ApoE−/−mice into C57BL/6Jmice (n = 8-12/group; one-way ANOVA/Dunnett test of Cx3cr1GFP/GFP versus any other group *P ≤ 0.0001; Mann-Whitney U-test, Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/− *P = 0.0006).",
    "ncbi_link": "ApoE: 11816
Cx3cr1: 13051"
  },
  {
    "caption": "Quantitative RT-PCR of FasLmRNA normalized with β-actinmRNA of 2-month-, 12-month-, and 2-month-old mice after 4 days of light challenge of C57BL/6 and Cx3cr1GFP/GFP mouse RPE/choroid plexus (aging: n = 5-6/group; Mann-Whitney U-test: 12 months *P = 0.0129; 4 days light challenge: n = 7-8/group; *P = 0.029).",
    "ncbi_link": "β-actin: 
Cx3cr1: 13051
FasL: 14103"
  },
  {
    "caption": "Immunohistochemistry of FASL (red) and IBA-1 (green) of a RPE flatmounts and sections (insets, Hoechst staining blue) from a 12-month-old WT (B) and Cx3cr1GFP/GFP(C) mouse (representative of three independent experiments, immunostainings omitting the primary antibody served as negative controls).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Quantitative RT-PCR of FasLmRNA normalized with β-actinmRNA of 12-month-old C57BL/6 RPE/choroid plexus extracts 3 h after subretinal injection of C57BL/6J macrophages or Cx3cr1GFP/GFP macrophages (n = 6 per group), Mann-Whitney U-test, *P = 0.0087.",
    "ncbi_link": "β-actin: 
Cx3cr1: 13051
FasL: 14103"
  },
  {
    "caption": "IBA-1-stained RPE flatmounts of 2-month-old C57BL/6J, Faslgld/gld, and Faslpr/lpr mice after 4 days of light challenge.Quantification of subretinal IBA-1+ mononuclear phagocytes in control (left) and 4-day light-challenged (right) 2-month-old mice of the indicated strains (n = 6-10/group ANOVA/Dunnett test at 4-day light challenge: C57BL/6J versus FasLgld/gld and C57BL/6J versus Faslpr/lpr both *P < 0.0001; Mann-Whitney U-test at 4-day light challenge: C57BL/6J versus FasLgld/gld *P < 0.0001; C57BL/6J versus Faslpr/lpr *P < 0.0001).",
    "ncbi_link": "Fas: 14102
Fasl: 14103
FasL: 14103"
  },
  {
    "caption": "Quantification of subretinal CFSE+F4/80+macrophages on RPE and retinal flatmounts 24 h after subretinal injection of C57BL/6JCFSE+macrophages into C57BL/6J and FasLgld/gldmice and Faslpr/lprmacrophages into C57BL/6Jmice (n = 10-15/group, one-way ANOVA/Dunnett test: C57BL/6Jmacrophages inj. into C57BL/6Jmice versus C57BL/6Jmacrophages inj. into Fasgld/gldmice *P = 0.0002; C57BL/6Jmacrophages inj. into C57BL/6Jmice versus Faslpr/lprmacrophages inj. into C57BL/6Jmice *P < 0.0001. Mann-Whitney U-test: C57BL/6Jmacrophages inj. into C57BL/6Jmice versus C57BL/6Jmacrophages inj. into FasLgld/gldmice *P < 0.0001; C57BL/6Jmacrophages inj. into C57BL/6Jmice versus Faslpr/lprmacrophages inj. into C57BL/6Jmice *P < 0.0001).",
    "ncbi_link": "Fas: 14102
FasL: 14103"
  },
  {
    "caption": "Quantification of subretinal CFSE+F4/80+ macrophages on RPE and retinal flatmounts 24 h after subretinal injection of Cx3cr1GFP/GFP CFSE+ macrophages into C57BL/6J with or without the Fas agonist MegaFasL (calculated intraocular concentrations 1 ng/ml; n = 7-8; Mann-Whitney U-test: *P = 0.014).",
    "ncbi_link": "Cx3cr1: 13051
Fas: 14102"
  },
  {
    "caption": "Quantitative RT-PCR of FasLmRNA normalized with β-actinmRNA of 12-month-old C57BL/6 RPE/choroid plexus 3 h after subretinal injection of PBS (PBS; n = 36), IL-6 (n = 17), and APOE3 (n = 21); calculated intraocular concentrations: 5 ng/ml and 10 μg/ml, respectively; one-way ANOVA/Dunnett post hoc test PBS versus IL-6 *P = 0.038; t-test PBS versus IL-6 *P = 0.043.",
    "ncbi_link": "β-actin: 
FasL: 14103"
  },
  {
    "caption": "Quantitative RT-PCR of IL-6mRNA normalized with S26mRNA of C57BL/6J and Cx3cr1GFP/GFP, and Cx3cr1GFP/GFP ApoE−/− peritoneal macrophages cultured for 24 h with CX3CL1 (n = 5 per group, one-way ANOVA/Bonferroni post hoc multi-comparison tests: C57BL/6J versus Cx3cr1GFP/GFP *P < 0.0001 and Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/−‡P < 0.0001. Mann-Whitney U-test: C57BL/6J versus Cx3cr1GFP/GFP *P = 0.0079 and Cx3cr1GFP/GFP versus Cx3cr1GFP/GFPApoE−/−‡P = 0.0079. The experiment was repeated twice with similar results.).",
    "ncbi_link": "S26: 
ApoE: 11816
Cx3cr1: 13051
IL-6: 16193"
  },
  {
    "caption": "Orthogonal and lateral Z-stack projection of IL-6 (D, red), IBA-1+ (E, green), and phalloidin (E, blue) of IBA+ mononuclear phagocytes adjacent to the phalloidin+ RPE of a retinal flatmount from a 12-month-old Cx3cr1GFP/GFP mouse. (Representative of three independent experiments, immunostainings omitting the primary antibody served as negative controls).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "Quantification of subretinal CFSE+F4/80+ macrophages on RPE and retinal flatmounts 24 h after subretinal injection of C57BL/6J CFSE+ macrophages into C57BL/6J with or without IL-6 (n = 15-20/group; calculated intraocular concentrations of 5 ng/ml. Mann-Whitney U-test: *P < 0.0001).Quantification of subretinal CFSE+F4/80+macrophages on RPE and retinal flatmounts 24 h after subretinal injection of Cx3cr1GFP/GFPCFSE+Mϕs into C57BL/6J with control (IgG, n = 16) or anti-IL-6 antibody (aIL-6 Ab, n = 8; calculated intraocular concentrations 5 μg/ml; per group. Mann-Whitney U-test: *P = 0.0036).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "7 day laser-injured IBA-1 (green) and CD102 (red) double-stained RPE flatmounts of control IgG- (I) and anti-IL-6-treated (J) Cx3cr1GFP/GFP mice.Quantification of subretinal IBA-1+ mononuclear phagocytes/impact localized on the lesion surrounding RPE of Cx3cr1GFP/GFP mice treated with control IgG, IL-6-, or CD14-blocking antibodies (calculated intraocular concentration 5 μg/ml; n = 13-14/group, one-way ANOVA/Dunnett's post hoc tests of IgG versus any other group *P < 0.001. Mann-Whitney U-test IgG versus anti-IL-6 *P = 0.0021; IgG versus anti CD14*P = 0.0028).",
    "ncbi_link": "Cx3cr1: 13051"
  },
  {
    "caption": "(F) Examples of expression levels of Treg signature genes  Foxp3, Il10ra, Nrp1, Ikzf4 and Ccr6; and examples of expression levels of genes upregulated in Tet2/3 DKO Treg  cells Eomes, Ccl4, Chek1  and Fn1. The Y-axis shows FPKM (Fragment Per Kilobase per Million reads), the X-axis shows the different cell types. Error bars show mean ± S.D. from two (CD4+ naïve T cells) or four (WT and Tet2/3 DKO Treg) biological replicates.",
    "ncbi_link": "Ccl4: 20303
Ccr6: 12458
Chek1: 12649
Eomes: 13813
Fn1: 14268
Foxp3: 20371
Ikzf4: 22781
Il10ra: 16154
Nrp1: 18186
Tet2: 214133"
  },
  {
    "caption": "(D) Genome browser view of  CMS-IP data showing CMS (5hmC) distribution at  Il2ra and Foxp3 locus for CD4+ naïve T cells  and WT Treg cells. Hydroxymethylated regions (hmRs) and DhmRs are shown on the top; conservation (cons) is shown at the bottom.",
    "ncbi_link": "Foxp3: 20371
Il2ra: 16184"
  },
  {
    "caption": "(E) Genome browser view of DNA methylation patterns of Hopx  and Il10 loci for  CD4+ naïve T cells, WT Treg cells and Tet2/3 DKO  Treg cells. Differentially hydroxymethylated regions (DhmRs) and differentially methylated CpGs (DM-CpGs) are shown on top of the tracks. Conservation track (Cons) and denotation of all CpGs are shown at the bottom. WGBS  data are from two biological replicate samples.",
    "ncbi_link": "Hopx: 74318
Il10: 16153
Tet2: 214133"
  },
  {
    "caption": "(E) Genome browser view of chromatin  accessibilities at  Hopx and Il10 loci for  CD4+ naïve T cells, WT Treg  cells and Tet2/3 DKO Treg cells. DhmRs, DM-CpGs  and DARs (shaded) are shown on top of the tracks. Conservation track (Cons) is shown at the bottom.",
    "ncbi_link": "Hopx: 74318
Il10: 16153
Tet2: 214133"
  },
  {
    "caption": "(H-J) Box-and-whisker plots of  DNA methylation  levels for DM-CpGs less methylated  in TGFβ + RA + VitC iTregs vs TGFβ iTregs (H), DM-CpGs less methylated  in WT Treg cells vs  CD4+ naïve T cells (I) and DM-CpGs less  methylated in WT Treg cells vs Tet2/3 DKO Treg cells (J). DM-CpGs denotes the CpGs in the respective cell types used for the comparison. Boxplots show the median and quartiles with the whiskers extending to the most extreme data point within 1.5 times the interquartile range. P-values are shown above relevant comparisons and are calculated using an analysis of variances with Tukey's post-hoc test. Data are from two biological replicates.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "(C)  ChIP-qPCR  showing STAT5 occupancy at Foxp3 CNS2   and  IL2Rα IN1b  regions in TGFβ and TGFβ  + RA  + VitC iTregs  without or with 3 U/ml IL-2 restimulation. GMPR is a negative control region. Data are from two biological replicates.",
    "ncbi_link": "Foxp3: 20371
GMPR: 66355
IL2Rα: 16184"
  },
  {
    "caption": "(C) Immunofluorescence staining of the spinal cord from GW7, GW8, and GW10 for a dorsal marker (PAX7, green), neuronal precursor marker (ASCL1, red), and nuclei marker (DAPI, blue). Images show the neuronal differentiation process on the dorsal side of the spinal cord. Scale bar: 100 μm.",
    "ncbi_link": "ASCL1: 429
PAX7: 5081"
  },
  {
    "caption": "(C) Violin plot showing the expression of selected genes. EGFR+ Cluster 14 is circled with a red dotted line.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(D) Violin plots produced by VlnPlot function of Seurat package representing changes in expression of EGFR, DLL1, MIAT, and FAM189A2 in cluster 14 with development based on snRNA counts data.",
    "ncbi_link": "DLL1: 28514
EGFR: 1956
FAM189A2: 9413
MIAT: 440823"
  },
  {
    "caption": "(F-G) Confocal  images and statistical analysis showing LacCer/LyTr colocalization  in MLIV patient fibroblasts  which were mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector and treated with either DMSO  or TPC2-A1-P (30 µM, 16h). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's G, multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "mCherry: 
TPC2: 219931"
  },
  {
    "caption": "(J-K) Confocal  images (J) and statistical analysis (K) of NPC1 patient fibroblasts  treated with 50 nM mock siRNA (siSCR) or siRNA targeting TPCN2  (siTPC2) for 72 hours. Cells were then treated with DMSO  or  TPC2-A1-P (30 µM). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, Tukey's (K) multiple comparisons test. *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "TPC2: 219931
TPCN2: 219931"
  },
  {
    "caption": "Confocal  images (E-F) of MLIV patient fibroblasts  mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector (white arrow heads) and treated with either DMSO  or TPC2-A1-P (30 µM, 48h).",
    "ncbi_link": "mCherry: 
TPC2: 219931"
  },
  {
    "caption": "statistical analysis (G) of MLIV patient fibroblasts  mock-electroporated and treated with DMSO  or electroporated with a gain-of-function hTPC2(M484L/G734E):mCherry  TOPO 3.1 vector (white arrow heads) and treated with either DMSO  or TPC2-A1-P  (30 µM, 48h). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); one-way ANOVA, post hoc Bonferroni's multiple comparisons test *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "mCherry: 
TPC2: 219931"
  },
  {
    "caption": "Confocal  images and statistical analysis of human  CTR patient fibroblasts  treated with 50 nM mock siRNA (siSCR) or siRNA targeting TPCN2  (siTPC2) for 72 hours. Cells were then treated with DMSO  Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells) two-tailed Student's t-test *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "TPC2: 219931
TPCN2: 219931"
  },
  {
    "caption": "Confocal  images and statistical analysis of human NPC1 patient fibroblasts  treated with 50 nM mock siRNA (siSCR) or siRNA targeting TPCN2  (siTPC2) for 72 hours. Cells were then treated with DMSO  or TPC2-A1-P (30 µM). Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells); two-tailed Student's t-test K). *p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "TPC2: 219931
TPCN2: 219931"
  },
  {
    "caption": "Cortical neurons were differentiated from iPSCs, generating  lysosomal storage disease neurons  and isogenic controls. (C-D) Western blot  analysis of  cathepsin B (CtsB) in CTR and MCOLN1IVS3-2A>G neurons  treated with TPC2-A1-P (30 µM) or DMSO. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); two-tailed Student's t-test (C). **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "Cortical neurons  were differentiated from iPSCs, generating  lysosomal storage disease neurons  and isogenic controls. Cortical neurons were treated with compounds and acidic compartments stained  with LysoTracker (LyTr). Endolysosomal  expansion was observed in MCOLN1IVS3-2A>G, CLN3D416G and CLN3ΔEx4-7 neurons, which was ameliorated by TPC2-A1-P  (30 µM) treatment. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); one-way ANOVA, post hoc Tukey's multiple comparisons test **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "CLN3: 1201
MCOLN1: 57192"
  },
  {
    "caption": "Cortical neurons were differentiated from iPSCs, generating lysosomal storage disease neurons  and isogenic controls. (H-I)  Electron microscopy analysis of neuronal rosettes (neuronal progenitor cells, NPC) treated with DMSO or TPC2-A1-P. TPC2-A1-P treatment significantly decreased the number of inclusion bodies (black arrow heads) in MCOLN1IVS3-2A>G. CLN3D416G and CLN3ΔEx4-7 lacked an appropriate assay window and showed no significant accumulation of  inclusion bodies. However, CLN3ΔEx4-7 NPC  showed significantly more mitochondria  with aberrant cristae  numbers (white arrow heads), a phenotype which was rescued by TPC2-A1-P (30 µM) treatment. Statistics: Shown are mean values ± SEM. n > 3 technical and biological replicates for each tested condition (each dot represents an imaged frame containing several cells, obtained from at least three distinct neuronal  differentiations); one-way ANOVA, post hoc Tukey's multiple comparisons test **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001.",
    "ncbi_link": "CLN3: 1201
MCOLN1: 57192"
  },
  {
    "caption": "(D) A cDNA array was used to map TPC2  transcripts in the human brain.",
    "ncbi_link": "TPC2: 219931"
  },
  {
    "caption": "Electropherograms of the XRCC4 genomic region encompassing the nucleotide substitutions in available members of the family.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "Quantitative real-time PCR of XRCC4 relative to GAPDH mRNA in affected (II-1 and II-2) and control (CT1 and CT2) fibroblasts. Each value refers to the mean of three independent experiments performed in duplicate. Error bars indicate the standard deviation.",
    "ncbi_link": "GAPDH: 
XRCC4: 7518"
  },
  {
    "caption": "γ-H2AX nuclear foci in XRCC4wt and mutant fibroblasts (XRCC4m/m1 and XRCC4m/m2) were determined at different times after irradiation with 0.5 Gy of γ-rays. Values, subtracted of their non-irradiated control (1.3 foci/nucleus in XRCC4wt cells and 1.4 and 0.9 foci/nucleus in XRCC4m/m1 and XRCC4m/m2 cells, respectively), are the mean ± SD of three independent experiments.Percentages of γ-H2AX foci in XRCC4wt and XRCC4m/m fibroblasts (pooled values) remaining at the indicated time-points.Immunofluorescence micrographs of γ-H2AX foci in XRCC4wt and XRCC4m/m fibroblasts.Data information: ***P < 0.001; **P < 0.01; *P < 0.05 (XRCC4m/m vs. XRCC4wt cells), two-way ANOVA, Bonferroni post hoc test.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "A, B Percentages of γ-H2AX nuclear foci remaining in CENP-F-negative (A) and CENP-F-positive (B) cells at the indicated time-points after irradiation with 0.5 Gy of γ-rays. Values, subtracted of their non-irradiated controls, are the mean ± SD of three independent experiments. ***P < 0.001; *P < 0.05 (XRCC4m/m versus XRCC4wt cells), two-way ANOVA, Bonferroni post hoc test.C Immunofluorescence micrographs of γ-H2AX foci in CENP-F-positive and negative fibroblasts at 2 h after irradiation. Arrow heads indicate the CENP-F-positive cells.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "RAD51 foci in XRCC4wt and XRCC4m/m fibroblasts irradiated with 0.5 Gy of γ-rays. Values are the mean ± SD of three independent experiments. ***P < 0.001; **P < 0.01 (XRCC4m/m versus XRCC4wt cells), two-way ANOVA, Bonferroni post hoc test.Immunofluorescence micrographs of RAD51 foci in XRCC4wt and XRCC4m/mfibroblasts. Arrowheads indicate the CENP-F-positive cells.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "XRCC4wt and XRCC4m/m cells irradiated with 0.5 Gy of γ-rays were exposed to the PARP1 inhibitor 3′-AB or to solvent (DMSO). The γ-H2AX foci number is the mean ± SD of three independent experiments. *P < 0.05 (XRCC4m/m + 3′-AB versus XRCC4m/m + DMSO), ***P < 0.001 (XRCC4m/m + 3′-AB versus XRCC4wt + 3′-AB), two-way ANOVA, Bonferroni post hoc test.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "A, B Percentages of DSBs repaired in increasing time intervals (0.5-2 h, 0.5-6 h, 0.5-24 h) were calculated in XRCC4wt (A) and XRCC4m/m (B) cells from the number of γ-H2AX foci in presence or absence of a PARP-1 inhibitor, 3′-AB. **P < 0.01 (XRCC4m/m + 3′-AB versus XRCC4m/m + DMSO), two-way ANOVA, Bonferroni post hoc test.",
    "ncbi_link": "XRCC4: 7518"
  },
  {
    "caption": "D) Immunofluorescent images of crypts from CAG-LC3-GFP-RFP and Lgr5-GFP mice 6h post-irradiation. Sections were stained for γH2AX, E-cadherin, and either LC3-RFP or Lgr5-GFP respectively. E) Quantification of the number of γH2AX foci in cells with RFP+ puncta, without autophagic puncta, or in Lgr5+ CBCs. N=3 mice/group, 40-80 cells quantified/mouse.",
    "ncbi_link": "GFP: 
RFP: 
Lgr5: 14160
LC3: 67443///66734"
  },
  {
    "caption": "A LC3 punctum formation in WT and GCN5 KO HeLa cells (Scale bars, 10 µm).",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "Immunoblot showing LC3-II formation in WT or GCN5 KO HeLa cells in the presence or absence of the lysosome inhibitor Baf.",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "D Formation of LC3 puncta in GCN5 KO HeLa cells overexpressing Myc-tagged GCN5 or GCN5-E575Q (Scale bars, 10 µm).",
    "ncbi_link": "Myc: 
GCN5: 2648"
  },
  {
    "caption": "Formation of LC3 puncta in HeLa cells overexpressing GFP-GCN5 with or without Baf treatment",
    "ncbi_link": "GFP: 
GCN5: 2648"
  },
  {
    "caption": "Formation of LC3 puncta in HeLa cells overexpressing GFP-GCN5 with or without Baf treatment (Graph represents data from three independent experiments with ≥ 30 cells per condition; mean ± SEM; *p < 0.05, **p < 0.01, Student's t-test; Scale bar, 10 µm).",
    "ncbi_link": "GFP: 
GCN5: 2648"
  },
  {
    "caption": "H LC3-II formation in GFP-GCN5-overexpressing HeLa cells.",
    "ncbi_link": "GFP: 
GCN5: 2648"
  },
  {
    "caption": "I GFP-p62 levels in HEK293 cells stably expressing GFP-p62. The cells were cultured with GCN5 siRNA with or without CQ.",
    "ncbi_link": "GFP: 
GCN5: 2648
p62: 8878"
  },
  {
    "caption": "J PDLIM1 and IFT20 protein levels in GCN5 KO HEK293 cells with or without transfection of GFP-GCN5 and addition of CQ.",
    "ncbi_link": "GFP: 
GCN5: 2648"
  },
  {
    "caption": "K Representative images of mCherry-Atg8a (red) and DAPI (blue) in Drosophila larval fat body in which dGcn5 is overexpressed (OE) or silenced (KD) using the pan-fat body driver (cg-GAL4). Drosophila (cg-GAL4/+) was used as the control (Graph represents data from three independent experiments with ≥ 30 cells per condition; mean ± SEM; *p < 0.05, ***p < 0.001, Student's t-test; Scale bars, 10 µm).",
    "ncbi_link": "GAL4: 855828
dGcn5: 39431"
  },
  {
    "caption": "A LAMP1 puncta (green) and DAPI (blue) in WT and GCN5 KO HEK293 cells (Scale bars, 10 µm).",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "B Fluorescence-activated cell sorting analysis of WT and GCN5 KO HEK293 cells stained with LysoTracker. Fluorescence intensity of 10,000 cells per sample was measured.",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "C Immunoblot showing lysosomal protein levels in three independent clones of GCN5 KO HEK293 cells. CTSD HC, cathepsin D heavy chain.",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "D LAMP1 puncta in GCN5 KO HEK293 cells overexpressing Myc-tagged GCN5 or GCN5-E575Q (Scale bars, 10 µm).",
    "ncbi_link": "Myc: 
GCN5: 2648"
  },
  {
    "caption": "F Hexosaminidase activity in GCN5 KO HEK293 cells (mean ± SEM; n = 3 independent experiments; ***p < 0.001, Student's t-test).",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "G Degradation of EGFR in WT and GCN5 KO HEK293 cells in the presence or absence of CQ.",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "H Representative images of LysoTracker staining (red) and DAPI (blue) in Drosophila larval fat body in which dGcn5 is overexpressed (OE) or silenced (KD). Drosophila (cg-GAL4/+) was used as the control (Graph represents data from three independent experiments with ≥ 30 cells per condition; mean ± SEM; *p < 0.05, **p < 0.01, Student's t-test; Scale bars, 10 µm).",
    "ncbi_link": "GAL4: 855828
dGcn5: 39431"
  },
  {
    "caption": "A Quantification of LC3 puncta in WT, GCN5 KO and GCN5/TFEB DKO HeLa cells in the presence or absence of Baf (Graph represents data from three independent experiments with ≥ 30 cells per condition; mean ± SEM; ***p < 0.001, Student's t-test).",
    "ncbi_link": "GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "B Immunoblot showing LC3-II formation in WT, GCN5 KO and GCN5/TFEB DKO HeLa cells in the presence or absence of Baf.",
    "ncbi_link": "GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "C Quantification of LAMP1 puncta in WT, GCN5 KO and GCN5/TFEB DKO HEK293 cells (Graph represents data from three independent experiments with ≥ 30 cells per condition; mean ± SEM; ***p < 0.001, Student's t-test).",
    "ncbi_link": "GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "D Immunoblot showing LAMP1 levels in WT, GCN5 KO and GCN5/TFEB DKO HEK293 cells.",
    "ncbi_link": "GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "E Acetylation of TFEB-Flag in stable TFEB-Flag-expressing HEK293 cells with overexpression of individual histone acetyltransferases as indicated. TFEB-Flag was immunoprecipitated with anti-Flag beads and analyzed by immunoblot using anti-acetyl-lysine (Ace-lys).",
    "ncbi_link": "Flag: 
TFEB: 7942"
  },
  {
    "caption": "F TFEB-Flag acetylation in the stable TFEB-Flag-expressing HEK293 cells transfected with Myc-tagged GCN5 or GCN5-E575Q after incubation with GCN5 siRNA for 48 h.",
    "ncbi_link": "Flag: 
Myc: 
GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "J Acetylation of Flag-tagged TFEB or TFEB mutants expressed in HEK293 cells. 3KR: Lys 116, Lys 274, and Lys 279 were replaced by Arg.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "A RT-qPCR analysis of the expression of TFEB target genes in WT, GCN5 KO and GCN5/TFEB DKO HEK293 cells. Data information: In this Figure, data are presented as mean ± SEM; n = 3 independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, Student's t-test.",
    "ncbi_link": "GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "B RT-qPCR analysis of dMitf target gene expression in Drosophila larval fat body with silencing of dGcn5. Data information: In this Figure, data are presented as mean ± SEM; n = 3 independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, Student's t-test.",
    "ncbi_link": "dGcn5: 39431
dMitf: 3885647"
  },
  {
    "caption": "C Expression of TFEB target genes in HEK293 cells transfected with or without TFEB-WT or TFEB-3KR. Data information: In this Figure, data are presented as mean ± SEM; n = 3 independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, Student's t-test.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "D, E Luciferase activity measured in WT, GCN5 KO and GCN5/TFEB DKO HEK293 cells (D), and in HEK293 cells with TFEB-WT or TFEB-3KR transfection (E). The cells were transfected or co-transfected with a TFEB-luciferase reporter. 3KR: Lys 116, Lys 274, and Lys 279 were replaced by Arg. Data information: In this Figure, data are presented as mean ± SEM; n = 3 independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, Student's t-test.",
    "ncbi_link": "luciferase: 
GCN5: 2648
TFEB: 7942"
  },
  {
    "caption": "A Subcellular localization of TFEB in WT or GCN5 KO HEK293 cells treated with or without Torin1 (Scale bars, 10 µm).",
    "ncbi_link": "GCN5: 2648"
  },
  {
    "caption": "C ChIP-qPCR analysis of TFEB binding to the promoter of its target genes CLCN7, GLA and CTSD. Normal mouse IgG and primers against the upstream region lacking CLEAR sites (up) were used as negative controls (mean ± SEM; n = 3 independent experiments; *p < 0.05, **p < 0.01, ***p < 0.001, Student's t-test).",
    "ncbi_link": "CLCN7: 1186
CTSD: 1509
GLA: 2717
TFEB: 7942"
  },
  {
    "caption": "D Electrophoresis mobility shift assay of TFEB binding to the promoter of GLA. A DNA fragment from the GLA promoter containing the TFEB binding site was incubated with purified recombinant TFEB or each of the TFEB mutants, and was subjected to electrophoresis. Asterisk indicates the DNA fragment from the GAPDH promoter which was used as a TFEB non-binding DNA control.",
    "ncbi_link": "GAPDH: 2597
GLA: 2717
TFEB: 7942"
  },
  {
    "caption": "I TFEB homodimer formation detected by glutaraldehyde (GA) crosslinking. Purified recombinant GST-tagged TFEB or TFEB mutants was incubated with or without glutaraldehyde, then the products were analyzed by immunoblotting using anti-TFEB.",
    "ncbi_link": "GST: 
TFEB: 7942"
  },
  {
    "caption": "E LC3-II formation in HeLa cells transfected with Flag-tagged TFEB or TFEB mutants after TFEB RNAi. The cells were treated with or without amino acid starvation.",
    "ncbi_link": "Flag: 
TFEB: 7942"
  },
  {
    "caption": "F GFP-p62 levels in HEK293 cells stably expressing GFP-p62. The cells were treated with or without addition of CQ.",
    "ncbi_link": "GFP: 
p62: 8878"
  },
  {
    "caption": "Representative images of mCherry-Atg8a (red) (G) in Drosophila larval fat body in which dMitf or dMitf-2KQ (K445Q/K450Q) was overexpressed. Drosophila (cg-GAL4/+) was used as the control and DAPI staining (blue) was used to indicate the cell nucleus (Scale bars, 10 µm).",
    "ncbi_link": "GAL4: 855828
dMitf: 3885647"
  },
  {
    "caption": "Representative images of LysoTracker (red) staining (H) in Drosophila larval fat body in which dMitf or dMitf-2KQ (K445Q/K450Q) was overexpressed. Drosophila (cg-GAL4/+) was used as the control and DAPI staining (blue) was used to indicate the cell nucleus (Scale bars, 10 µm).",
    "ncbi_link": "GAL4: 855828
dMitf: 3885647"
  },
  {
    "caption": "The level of insoluble Tau protein in the head of adult Drosophila with or without CQ feeding. The indicated genes were transgenically expressed in the eyes of the Drosophila using the GMR-Gal4 driver. Drosophila (GMR-Gal4/+) was used as the control.",
    "ncbi_link": "GMR: 
Gal4: 855828"
  },
  {
    "caption": "The level of insoluble Tau protein in the head of adult Drosophila with or without CQ feeding. The indicated genes were transgenically expressed in the eyes of the Drosophila using the GMR-Gal4 driver. Drosophila (GMR-Gal4/+) was used as the control.",
    "ncbi_link": "GMR: 
Gal4: 855828"
  },
  {
    "caption": "C Representative light micrographs of adult Drosophila eyes expressing the indicated transgenes under the control of the GMR-Gal4 driver. The Drosophila were fed with or without CQ. Drosophila (GMR-Gal4/+) was used as the control.",
    "ncbi_link": "GMR: 
Gal4: 855828"
  },
  {
    "caption": "D. Tyrosine phosphorylation of LORE in vivo. Two-week-old 35S:LORE-FLAG complementation plants were subjected to immunoprecipitation with anti-FLAG agarose beads. A23 (40 μM) was used to inhibit the protein phosphorylation, and the treatments were same as in (A). Protein abundance of precipitated LORE-FLAG was detected by immunoblotting. The tyrosine phosphorylation was probed by anti-pTyrosine (α-pY) antibody. Similar results were observed in three biological replicates.",
    "ncbi_link": "FLAG: 
LORE: 842432"
  },
  {
    "caption": "B. Y600 mutation reduced LORE kinase activity. MBP-tagged LORE-CD and LORE-Y600F-CD (Y600 tyrosine was substituted with phenylalanine, F) were subjected to kinase reactions. The kinase dead mutant LOREK516E served as a negative control. Autophosphorylated LORE was visualized by autoradiography following SDS-PAGE gel electrophoresis. Protein abundance was stained by CBB.",
    "ncbi_link": "LORE: 842432"
  },
  {
    "caption": "C. LORE Y600 is phosphorylated in plants. Two-week-old pLORE:LORE-FLAG complementation plant leaves were subjected to immunoprecipitation (IP) with anti-FLAG agarose beads. Y600 specific phosphorylation antibody was used to detect Y600 phosphorylation in LORE. The experiment was repeated three times with similar results.",
    "ncbi_link": "FLAG: 
LORE: 842432"
  },
  {
    "caption": "D. 3-OH-C10:0 induced Y600 phosphorylation. Two-week-old pLORE:LORE-FLAG complementation plants were treated with 1 μM 3-OH-C10:0 at indicated times. Plant leaves were subjected to anti-FLAG IP. Phosphorylation level of Y600 was detected by anti-pY600 antibody. The experiment was repeated three times with similar results.",
    "ncbi_link": "FLAG: 
LORE: 842432"
  },
  {
    "caption": "E. Y600 mutation abolished the ROS burst triggered by 3-OH-C10:0. The transgenic plants were treated with 3-OH-C10:0 and ROS burst was measured. WT(6-1) and WT(10-3) are two independent complementation lines with LORE; Y600F(2-6) and Y600F(7-1) are two independent lines complemented with LOREY600F; and kinase-dead LOREK516E was transformed to lore mutant as a negative control. The 2-3 and 5-2 are two independent lines. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01).",
    "ncbi_link": "lore: 842432
LORE: 842432"
  },
  {
    "caption": "A. LORE interacts with specific RLCKs (PBL34/35/36) in yeast. BD-LORE-CD and AD-PBLs were co-transformed to yeast cells and were screened on synthetic dextrose media lacking leucine and tryptophan (SD/-Leu-Trp). The single yeast colonies were serially diluted onto SD/-Leu-Trp and SD/-Leu-Trp-His (SD media lacking leucine, tryptophan and histidine) to observe yeast cell growth. 3-AT(20 mM) was used to inhibit the autoactivation of LORE. Yeast co-transformed with pGADT7-T+pGBKT7-53(+) served as a positive control, and the yeast co-transformed with pGADT7-T+pGBKT7-lam(-) and AD-PBL39+BD-LORE served as the negative controls. EV, empty vector.",
    "ncbi_link": "GADT7: 
GBKT7: 
LORE: 842432"
  },
  {
    "caption": " C. Co-immunoprecipitation (Co-IP) of LORE with PBLs. 35S promoter-driven LORE-T7 and PBLs-FLAG were transiently co-expressed in N. benthamiana by agroinfiltration. Plant leaves were immunoprecipated with anti-FLAG beads and the proteins were immunoblotted by anti-FLAG antibody. Co-IP proteins were immunoblotted by anti-T7 antibody. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: 
PBL: "
  },
  {
    "caption": " D. LORE interacts with PBLs, revealed by split-luciferase assays. N. benthamiana leaves were co-infiltrated with Agrobacteria carrying 35S:LORE-nLUC and 35S:cLUC-PBLs. Images of chemiluminescence were obtained by applying 0.5 mM luciferin 36 h post infiltration. Similar results were observed in three biological replicates. ",
    "ncbi_link": "35S: 
PBL: 
LORE: 842432"
  },
  {
    "caption": " A. ROS burst in pbl34/35/36 triple mutant, induced by 3-OH-C10:0. Two-week-old seedlings were treated with 1 μM 3-OH-C10:0, and the ROS burst was measured. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01). ",
    "ncbi_link": "pbl34: 831360"
  },
  {
    "caption": " C. pbl34/35/36 triple mutant displayed decreased callose depositions in response to 3-OH-C10:0 treatment. Two-week-old seedlings were sprayed with 1 μM 3-OH-C10:0. The leaves were sampled for callose deposition assays 12 hrs later. The stained callose was counted for 1 mm2 of the leaves. Mock is solvent control. Scale bar=100μm.Values are means ± SD (n=6 leaves). (Student's t-test, **P< 0.01). ",
    "ncbi_link": "pbl34: 831360"
  },
  {
    "caption": " D. Root length of pbl34/35/36 triple mutant treated with 3-OH-C10:0. The Arabidopsis seedlings were grown on ½ MS containing 2.5 μM 3-OH-C10:0 for six days, and the root length was measured. Scale bar=0.4cm. Values are means ± SD (n=3 biological replicates). (ANOVA, P <0.01). ",
    "ncbi_link": "pbl34: 831360"
  },
  {
    "caption": " E. Disease phenotype of pbl34/35 double, pbl34/35/36 triple mutants and PBL34 overexpression plants. 35S:PBL34-FLAG was introduced to the Col-0 to generate the overexpression lines. The homozygous transgenic plants were used for the assays. The plants were sprayed with Pst DC3000 at a concentration of 1×109 cfu/ml. Plants were subjected to bacterial growth curve analysis at 3 dpi. OE-3# and OE-11# are two independent transgenic lines. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01). ",
    "ncbi_link": "35S: 
FLAG: 
pbl34: 831360
PBL34: 831360"
  },
  {
    "caption": " F. pbl34/35/36 triple mutant phenotype was rescued by PBL34. PBL34-HA was introduced to the triple mutant driven by its native promoter. Four-week-old homozygous seedlings were inoculated with 5×104 cfu/ml Pst DC3000 , and the leaves were subjected to bacterial growth curve analysis at 3 dpi. CM2-5 and CM7-3 are two independent transgenic lines. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01). ",
    "ncbi_link": "PBL34: 831360
pbl34: 831360"
  },
  {
    "caption": " B. Mutation of PBL34 T306/T310 significantly reduced its phosphorylation by LORE. Recombinant kinase dead PBL34* and PBL34*-2A (T306/T310 was mutated to A) were incubated with LORE-CD. Phosphorylation of PBL34 was visualized by 32P autoradiography. Protein abundance was revealed by CBB staining. ",
    "ncbi_link": "PBL34: 831360"
  },
  {
    "caption": " D. PBL34 phosphorylation is induced by 3-OH-C10:0. The protoplast of Col-0 was transformed with 35S:PBL34-FLAG and 35S:PBL34-2A-FLAG, respectively. Sixteen hours later, the protoplasts were treated with1 μM 3-OH-C10:0. Phosphorylated proteins were immunoprecipitated and detected by anti-pS/T antibody. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: 
FLAG: 
PBL34: 831360"
  },
  {
    "caption": " E. 3-OH-C10:0-induced PBL34 phosphorylation depends on LORE. The 35S:PBL34-FLAG was introduced to Col-0 and lore, respectively. Four-week-old homozygous transgenic plants were treated with 1 μM 3-OH-C10:0. Phosphorylated proteins were immunoprecipitated and detected by anti-pS/T antibody. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: 
FLAG: 
PBL34: 831360
lore: 842432"
  },
  {
    "caption": " F. PBL34 dissociated from LORE upon 3-OH-C10:0 activation. The 35S:LORE-FLAG plants were transformed with native promoter driven PBL34 (pPBL34:PBL34-HA). 100 nM flg22 or 1 μM 3-OH-C10:0 was sprayed onto plant leaves, and the leaves were sampled for assays15 min later. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: 
FLAG: 
PBL34: 831360
LORE: 842432"
  },
  {
    "caption": " G. Phosphorylation of PBL34K180E did not disassociate from LORE. The 35S:LORE-FLAG protoplasts were transfected with 35S:PBL34K180E-HA. 100nM flg22 or 1 μM 3-OH-C10:0 was used to treat the protoplasts. The protoplasts were sampled 15 min later. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: 
FLAG: 
PBL34: 831360
LORE: 842432"
  },
  {
    "caption": " H. PBL34 rescues pbl34/35/36 triple mutant ROS burst in response to 3-OH-C10:0. Treatment was same as in (E). pPBL34:PBL34-HA was introduced to pbl34/35/36 triple mutant, and the homozygous transgenic line was used for ROS burst assays. Values are means ± SD (n=6 biological replicates). (ANOVA, P <0.01). ",
    "ncbi_link": "pbl34: 831360
PBL34: 831360"
  },
  {
    "caption": " I. PTI marker gene expression in PBL34 complementation lines. The PTI marker genes FRK1 and NHL10 expression was examined by RT-qPCR in Col-0, pbl34/35/36, and CM-PBL34-2A lines after 3-OH-C10:0 treatments for 4 hrs. Values are means ± SD (n=6; ANOVA; p < 0.01). ",
    "ncbi_link": "PBL34: 831360
pbl34: 831360
FRK1: 816436
NHL10: 818171"
  },
  {
    "caption": " J. PBL34 phosphorylation at T306/T310 is essential for disease resistance. pbl34/35/36 triple mutants were complemented with PBL34 or PBL34-2A driven by its native promoter. The homozygous plants were pretreated with 3-OH-C10:0(C10) 1 d before pathogen inoculation. The plants were inoculated with 2×105 cfu/ml Pst DC3000, and the bacterial titer was analyzed at 3 dpi. Mock is solvent control. Letters indicate the difference from Col-0. Values are means ± SD (n=6; ANOVA; p < 0.01). ",
    "ncbi_link": "PBL34: 831360
pbl34: 831360"
  },
  {
    "caption": " B. LORE interacts with HopAO1 by Co-IP assays. 35S promoter-driven LORE-T7 and HopAO1-FLAG were transiently co-expressed in N. benthamiana by agroinfiltration. Plant leaves were immunoprecipated with anti-FLAG beads and immunoblotted by anti-FLAG. Coimmunoprecipitated proteins were immunoblotted by anti-T7. The experiment was repeated three times with similar results. ",
    "ncbi_link": "35S: "
  },
  {
    "caption": "  E. HopAO1 suppresses 3-OH-C10:0-triggered ROS burst. HopAO1 was ectopically expressed in Col-0 driven by estradiol-inducible promoter. 100μM estradiol was sprayed on Est:HopAO1 plants, and the leaf disc was used for ROS burst assays 12 hrs later. Values are means ± SD (n=6 biological replicates). ",
    "ncbi_link": "HopAO1: "
  },
  {
    "caption": " F. HopAO1 inhibits 3-OH-C10:0-induced disease resistance. The Est:HopAO1 plants were pretreated with 1 μM 3-OH-C10:0 (C10) and100 μM estradiol, and then the plants were inoculated with 5×104 cfu/ml Pst DC3000 24 hrs later. The bacterial titer was analyzed at 3 dpi. Values are means ± SD (n=6; ANOVA; p < 0.01 ",
    "ncbi_link": "HopAO1: "
  },
  {
    "caption": "(a) RT-PCR analysis of LC3, IL-8, CHOP and GADD34 in U2OS cells subjected to glutamine deprivation (−Q) or exposed to TPG (1 μM). (",
    "ncbi_link": "IL-8: 3576
CHOP: 1649
LC3: 440738///81631///84557
GADD34: 23645"
  },
  {
    "caption": "d) U2OS mCherry-GFP-LC3 cells were cultured in the presence (+Q) or absence (−Q) of glutamine for 18 h. Red vesicles denote autolysosomes, whereas yellow vesicles represent autophagosomes. Bars indicate numbers of yellow vesicles (autophagosomes) or red vesicles (autolysosomes) per cell±s.d. (e) Images of U2OS mCherry-GFP-LC3 cells cultured for 18 h in the presence (+Q) or absence (−Q) of glutamine. Scale bar, 10 μm.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) Immunoblot of autophagy-related proteins in U2OS cells expressing a control TALEN (U2OS-TAL2-C1) or two independent subcloned TALEN cell lines targeting ATG7 (U2OS-TAL2-A7, U2OS-TAL2-A8). p62 long and short refer to either long or short exposure times during film development.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(b) U2OS cells expressing an ATG7-TALEN (TAL2-ATG7) or control TALEN (TAL2-CTL) were subjected to glutamine starvation for 6 days followed by 6 days recovery in glutamine-replete medium. Cells were then stained with SRB and absorbance was read at 540 nM. Graph shows average results from five clonal sub-lines for each condition. The statistical significance (P value) was determined by a two-tailed, paired Student's t-test. P0.05. (c) Representative images of SRB-stained clones in b",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "d) IL-8 enzyme-linked immunosorbent assay (ELISA) of U2OS-TAL2-CTL-C1 (control) and U2OS-TAL2-ATG7-A8 (ATG7 knockout) following 24 h glutamine deprivation.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(d) RT-PCR analysis of IL-8 mRNA expression in U2OS cells after 24 h glutamine deprivation with or without CCI-779 or WYE-125132. Error bars in all figures represent s.d. of three biological replicates. OD, optical density.",
    "ncbi_link": "IL-8: 3576"
  },
  {
    "caption": "(b) RT-PCR analysis of IL-8 mRNA expression in U2OS cells transfected with two different siRNAs targeting JNK (JNK #1 and JNK #2) and subjected to 24 h glutamine deprivation.",
    "ncbi_link": "IL-8: 3576
JNK: 5602///5601///5599"
  },
  {
    "caption": "(d) Immunoblot analysis of JNK protein expression in JNK siRNA-treated cells.",
    "ncbi_link": "JNK: 5602///5601///5599
JNK: P45984///P53779///P45983///5602///5601///5599"
  },
  {
    "caption": "e) RT-PCR analysis of IL-8 expression in U2OS cells after 24 h glutamine deprivation with or without the JNK inhibitor SP600125 (JNKi).",
    "ncbi_link": "IL-8: 3576"
  },
  {
    "caption": "(g) IL-8 ELISA of U2OS cells transfected with two different siRNAs targeting IRE1 (IRE-A and IRE-B) and subjected to glutamine deprivation for 24 h.",
    "ncbi_link": "IRE1: 2081"
  },
  {
    "caption": "(h) RT-PCR analysis of IL-8 mRNA expression from experiment described in g. (i) RT-PCR analysis of CHOP mRNA expression from experiment described in g. (j) RT-PCR analysis of IRE1 mRNA expression from experiment described in g.",
    "ncbi_link": "IL-8: 3576
CHOP: 1649
IRE1: 2081"
  },
  {
    "caption": "(b) RT-PCR analysis of IL-8 and CHOP mRNA expression in U2OS cells starved of glutamine for 24 h and co-treated with DMαKG.",
    "ncbi_link": "IL-8: 3576
CHOP: 1649"
  },
  {
    "caption": "(A) Primary screen anti-CD8 antibody-uptake images for control cells (top) and SFT2D2 KD cells (bottom).",
    "ncbi_link": "SFT2D2: 375035"
  },
  {
    "caption": "(B) Cells stably expressing SFT2D2-Myc show localization of SFT2D2 to perinuclear membranes and endosomes, including VPS35-positive endosomes (arrowheads in inset). Treatment with nocodazole disperses the endosomes and even more clearly shows colocalization of SFT2D2-Myc and VPS35 (arrowheads in inset).",
    "ncbi_link": "perinuclear: "
  },
  {
    "caption": "(D) SNARE protein staining was compared for control and SFT2D2 KD HeLa cells and quantified. The graph shows the change in cellular intensity measured for each post-Golgi SNARE investigated. Images illustrate the increased cellular intensity of VAMP3 in SFT2D2 KD cells.",
    "ncbi_link": "SFT2D2: 375035"
  },
  {
    "caption": "(E) Control and SFT2D2 KD HeLa cell lysates were separated by LDS-PAGE and blotted for the indicated SNARE proteins or actin.",
    "ncbi_link": "SFT2D2: 375035"
  },
  {
    "caption": "(A) Primary screen anti-CD8 antibody-uptake images for control cells (top) and ZDHHC5 KD cells (bottom).",
    "ncbi_link": "ZDHHC5: 25921"
  },
  {
    "caption": "(C) Control and ZDHHC5 siRNA-treated SFT2D2-Myc cells were mixed and stained for ZDHHC5, Myc, and VPS35. KD cells are marked by an asterisk.",
    "ncbi_link": "ZDHHC5: 25921"
  },
  {
    "caption": "(D) Control and ZDHHC5 siRNA-treated HeLa cells were mixed and stained for ZDHHC5, α5-integrin, and VPS35. KD cells are indicated with an asterisk.",
    "ncbi_link": "ZDHHC5: 25921"
  },
  {
    "caption": "(E) Control (top) and ZDHHC5 KD (bottom) HeLa cells were fixed and stained for TGN46 and β1-integrin.",
    "ncbi_link": "ZDHHC5: 25921"
  },
  {
    "caption": "(A) Primary screen anti-CD8 antibody uptake images for control cells (top) and GRINA KD cells (bottom).",
    "ncbi_link": "GRINA: 2907"
  },
  {
    "caption": "(B) Control (top) and GRINA KD (bottom) HeLa cells were stained for Golgi marker GM130 and Golgi glycoprotein-1 (GLG1).",
    "ncbi_link": "GRINA: 2907"
  },
  {
    "caption": "(C) Cells stably expressing GFP-Rab6 were treated with GRINA siRNA (bottom) and compared to control cells (top) upon staining for TGN46 and VPS35.",
    "ncbi_link": "GRINA: 2907"
  },
  {
    "caption": "(D) Quantitation by western blotting of lysates from control and GRINA-silenced HeLa cells and GFP-Rab6 cells.",
    "ncbi_link": "GRINA: 2907
Rab6: 84084///51560///5870"
  },
  {
    "caption": "(B-E) Quantitative analysis of SFT2D2, ZDHHC5, and GRINA KD cells immunofluorescence using automated microscopy (see Experimental Procedures). (B) Representative images showing VPS35, TGN46, and CIMPR staining. Scale bar, 50 μm. (C) Quantitative analysis of CIMPR intensity at the Golgi indicates a significant increase in SFT2D2, ZDHHC5, or GRINA KD cells. (D) SFT2D2, ZDHHC5, and GRINA KD increase the Pearson's correlation coefficient for colocalization between CIMPR and retromer proteins VPS35 or SNX1 while decreasing the correlation between CIMPR and Golgi matrix protein GM130. In some cases, identical correlation coefficients were measured in the replicate experiments. (E) Quantitation of the TGN46 and GLG1 intensity in the three types of KD cells.",
    "ncbi_link": "GRINA: 2907
SFT2D2: 375035
ZDHHC5: 25921"
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control Human osteosarcoma U2OS stably expressing CALR-GFP and H2B-RFP were treated as described above and images were acquired once per hour for 12 h (A). For one representative experiment among three, the mean ± SEM of the average area of high CALR dots (normalized to the control at each timepoint) of quadruplicates is shown (B). Values are depicted as the area under the curve ± SD of triplicates",
    "ncbi_link": "CALR: 
GFP: 
H2B: 
RFP: "
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control Treated U2OS cells stably expressing HMGB1-GFP and H2B-RFP images were acquired every hour for 24 h (D). For one representative experiment among three, the mean ± SEM of the green fluorescence intensity in the nucleus (normalized to the control at each timepoint) of quadruplicates is depicted (E). For each cell, the speed of nuclear release (difference of HMGB1 nuclear green fluorescence intensity between two time points) was calculated. Values are depicted as the average speed of the nuclear release ± SD of quadruplicates",
    "ncbi_link": "GFP: 
H2B: 
HMGB1: 
RFP: "
  },
  {
    "caption": "Human osteosarcoma U2OS cells were treated with dactinomycin (DACT) at 0.5 or 1 µM, or with mitoxantrone (MTX) between 1 and 6 µM as positive control U2OS wild-type cells were treated with MTX or DACT as described above for 6 h. Then medium was refreshed and 24 h later, type I interferon response was assessed by transferring the supernatant on HT29 MX1-GFP reporter cells lines cells for additional 48 h. Human type 1α interferon (IFNα1) was also added on the cells as an additional positive control. Images were acquired by fluorescence microscopy and the number of positive cells was assessed based on the distribution of cellular green fluorescence intensity in IFNα1 versus control conditions (I). The percentage of MX1 positive cells was calculated and the mean ± SEM of five independent experiments is depicted",
    "ncbi_link": "GFP: 
MX1: "
  },
  {
    "caption": "U2OS cells stably expressing ATF4-reporter were treated as described above for 12 h. The expression and nuclear translocation of ATF4 was assessed by fluorescence microscopy and the nuclear green fluorescence intensity was quantified. Images are shown for untreated control cells (Ctr), THAPS and DACT at 1 µM",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "U2OS stably expressing ATF6-GFP were treated as described above and nuclear translocation of ATF6 was represented as the ratio of nuclear versus cytoplasmic green fluorescence intensity. Images are shown for untreated control cells (Ctr), THAPS and DACT at 1 µM",
    "ncbi_link": "ATF6: 
GFP: "
  },
  {
    "caption": "U2OS cells stably expressing venus in frame with alternatively spliced XBP1 (sXBP1) were treated as described above for 12 h. De novo expressed venus was measured intracellular. Images are shown for untreated control cells (Ctr), THAPS and DACT at 1 µM",
    "ncbi_link": "venus: 
XBP1: 7494"
  },
  {
    "caption": "U2OS wild-type and knock out for eIF2α kinases 1, 2, 3 and 4 cells were treated with 3 µM THAPS as a positive control for EIF2AK3-mediated eIF2α phosphorylation or with 1 µM DACT for 6 h. After fixation, cells were stained for peIF2α as described above and cytoplasmic intensity was quantified. Images are shown for untreated control cells (Ctr), THAPS and DACT at 1 µM",
    "ncbi_link": "eIF2α kinases 1: 27102"
  },
  {
    "caption": "U2OS CALR-RFP were injected subcutaneously (s.c) in the flank of nu/nu mice. Tumors were further injected with PBS (Ctr) (n=5), 0.5 mg/kg tunicamycin (TM) for 6 h (n=3) or 0.5 mg/kg DACT for 6 h (n=4) or 24 h (n=3). Tumor slices were cut and stained with a peIF2α antibody followed by an AlexaFluor-647 secondary antibody and counterstained with Hoechst 33342. Two slices per tumor were imaged for their DAPI, RFP and Cy5 signals. Out-of-focused images were removed from the dataset leading to the analysis of the following conditions: 8 x Ctr, 5 x TM, 8 x DACT 6 h and 6 x for DACT 24 h. PeIF2α was quantified measuring Cy5 intensity in the cytoplasm (K, L) and CALR translocation by measuring the coefficient variation (CV) of the RFP signal in the cytoplasm (M, N). Representative images of peIF2α are shown for Ctr, TM and DACT at 6 h (K), whereas images of CALR are shown for Ctr and DACT at 24 h",
    "ncbi_link": "CALR: 
RFP: "
  },
  {
    "caption": "Mice bearing WEHI 164 sarcomas were treated by systemic (intraperitoneal, i.p.) injections of DACT or PBS as a control (Ctr), and tumor were excised 9 days later for the quantitation of mRNA coding for IFNγ Two independent experiments were conducted with a total of 22 mice in the Ctr group and 23 mice in the DACT-treated group, with each data point indicating one tumor. The cycle threshold of the qRT-PCR of IFNγ was normalized to the one of the housekeeping gene peptidylpropyl isomerase A (Ppia) in each mouse and results are shown normalized with respect to controls as a dot plot depicting mean ± SD . The p-value (* p<0.05) was calculated by means of a Student's t test (B).",
    "ncbi_link": "Ppia: 
peptidylpropyl isomerase A: 
IFNγ: 15978"
  },
  {
    "caption": "A. Triple RNAscope in situ hybridization  showing Engrailed-1  (En1), Choline acetyltransferase  (ChAT) and Calbindin-1 (Calb1) expression  in the  lumbar spinal cord. En1  is expressed in  V1 interneurons, dorsal  (V1P) and ventral  (V1R) to the main ChAT-expressing motoneuron  pool. Ventral interneurons  correspond to  Renshaw cells as shown by Calb1 expression. Scale bar: 500 μm.",
    "ncbi_link": "Calb1: 12307
Calbindin-1: 12307
Choline acetyltransferase: 12647
ChAT: 12647
En1: 13798
Engrailed-1: 13798"
  },
  {
    "caption": "B.  RT-qPCR of RNA from the lumbar  enlargement at 4.5- and 16-months of age  shows stable En1  expression in WT at both ages  and a two-fold reduction of expression in heterozygous mice. Unpaired two-sided t-test. **p<0.005; ***p<0.0005. n=3. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "C. Triple staining EN1 IHC  (green), En1 RNAscope ISH (red) and ChAT RNAscope  (blue) demonstrating the double-staining  of En1  mRNA and protein (EN1) in the V1 interneuron  population (left panel insets, arrowheads point towards examples of double-stained V1 interneurons), and the presence of EN1  protein in large cells not expressing En1  mRNA (left panel) but expressing ChAT  (right panel insets). Scale bar: 500 µm, 30 µm for high magnification insets. D. Left: EN1  (red) detected with the LSBio antibody is localized  in ChAT-expressing neurons  (green) in the  ventral horns of the spinal cord. Right: EN1  signal is lost upon preincubation of the antibody with 1.5 M excess of recombinant hEN1. Scale bar: 50 µm.",
    "ncbi_link": "ChAT: 12647
En1: 13798"
  },
  {
    "caption": "A. Analysis of the number of En1+, Calb1+ and ChAT+ neurons  (triple RNAscope). At 4.5 months, WT and En1-Het mice  show no difference in the number of cells expressing En1, Calb1  or ChAT. Unpaired two-sided t-test. n=5-6. Data information: The analysis of neuron  number in A were performed once. Values are mean ± SD.",
    "ncbi_link": "Calb1: 12307
ChAT: 12647
En1: 13798"
  },
  {
    "caption": "D. Lumbar  level Cresyl violet staining  shows that, in contrast with small and medium size neurons  (interneurons  and γMNs, left and center panels), large size neurons  (αMNs, right panel) undergo progressive death first measured at 4.5 months. The values represent the average number of cells per  ventral horn. For the small neurons  (100-199 µm2), there was no main effect, two-way ANOVA for repeated measures for treatment group: F(1,43)=0.0017, p=0.968, ns. For the medium sized neurons  (200-299 µm2) two-way ANOVA for repeated measures for treatment group: showed no main effect F(1,43)=2.085, ns. For the large neurons (>300 µm2), two-way ANOVA for repeated measures showed a significant main effect F(1,43)=59.99, p<0.0001. Post-hoc comparisons were performed by unpaired two-sided t-test with equal SD comparing WT with En1-Het at each  time point (*p<0.05; **p<0.005; ***p<0.0005; ****p<0.0001). n=5 to 6. Data information: The longitudinal studies in D were performed once. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "E. Compared to WT mice, En1-Het mice  experience gradual strength loss. This loss is observed with the forepaw grip strength  (left panel), the inverted grid test (center panel and the hindlimb extensor reflex test (right panel). Strength loss is first observed between 2 and 3 months, thus before measurable αMN cell body  loss. Two-way ANOVA showed significant main effects for  grip strength  (F(1,136)=19.18, p<0.0001), inverted grid test (F(1,103)=143.1, p<0.0001) and extensor score  (F(1,103)=10.1, p<0.0001). Comparisons were made by unpaired two-sided t-test with equal SD comparing WT with En1-Het at each  time point  (*p<0.05; **p<0.005; ***p<0.0005; ****p<0.0001). n=4 to 20. Data information: The longitudinal studies in E were performed once. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "A. NMJs  of En1-Het and WT mice  show similar numbers of AChR  clusters (left panel) and late-occurring (15.5 months) decrease in endplate  area (center panel) and percentage of perforated endplates  (right panel). The number of AChR  clusters seems to decrease between 2 and 3 months, but two-way ANOVA showed no significant genotype effect (F(1,47)=0.1291, ns). There was a significant main effect for endplate  area (F(1,47)=5.778, p=0.0202) and for the percentage of perforated endplates  (F(1,47)=13.82, p=0.0005). Post hoc analysis revealed significant genotype differences at 15.5 month of age. Unpaired two-sided t-test with equal SD comparing WT with En1-Het at each time point (**p<0.005). n=4 to 8. Data information: The longitudinal study in A was performed once. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "B. Left panel illustrates the use of Alexa Fluor 488-conjugated  α-bungarotoxin (α-BTX, in green) and of neurofilament  and  synaptic vesicle glycoprotein antibodies (2H3  and SV2A, in red) to evaluate the percentage of fully occupied endplates  (>80% occupancy). The right panel shows that the % of fully occupied endplates  decreases progressively in the En1-Het mouse, starting between 3 and 4.5 months of age. Scale bar: 50µm. Two-way ANOVA showed a significant main effect (F(1,47)=45.45, p<0.0001). Unpaired two-sided t-test with equal SD comparing WT with En1-Het at each time point  (*p<0.05; **p<0.005). n=4 to 8. See details of analysis in the Methods section. Data information: The longitudinal study in B was performed once. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "A. Mice  were tested for strength at three months of age, before the onset of αMN  loss, but when strength has already decreased in En1-het mice  as measured in the forepaw grip strength,  inverted grid, and extensor reflex tests (left side of each graph). The next day, the En1-het mice  were separated into two groups. One group received buffer and the other group recombinant hEN1  (1 µg in 5 µl), injected at the L5 level. One and a half months later (4.5 months of age) En1-het mice  injected with hEN1 have recovered normal strength, in contrast with non-injected mice  or mice  injected with buffer. Unpaired two-sided t-test used at three months of age. ****p<0.0001. For 4.5-month comparisons, 1-way ANOVA followed by Tukey corrected post-hoc comparisons. ***p<0.0005; ****p<0.0001. n=9 to 31",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "B. Based on the results shown in A, a new experiment was performed with a second injection 12 weeks after the first injection at 3 months of age. Again, the injection at three months of age  restored strength and in mice  receiving the second injection strength was maintained an additional ten weeks or more compared to mice  receiving a single injection. The three strength graphs demonstrate a positive effect of the second injection with values intermediate between those measured in WT mice  and En1-Het mice  with a single injection. The percentage of fully occupied endplates  and the number of αMNs  are back to wild type values in En1-Het mice  injected twice. Two-way ANOVA revealed significant main effects for grip strength (F(2,81)=25.47, p<0.0001),  inverted grid (F(2,91)=51.96, p<0.0001) and extensor score  (F(2,104)=30.42, p<0.0001). At all times  groups were compared by Unpaired T-test with equal variances through 12 weeks. After, the groups were compared by Tukey corrected post-hoc comparisons (*p<0.05; **p<0.005; ***p<0.0005; ****p<0.0001). For the endplate  analysis and αMNs, groups were compared by 1-way ANOVA followed by Tukey corrected post hoc comparisons (*p<0.05; **p<0.005; ***p<0.0005; ****p<0.0001). n= 4 to 10.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "C. Intensity measurements demonstrates that the mean of SQTSM1/p62 expression  increases with age  in WT γMNs  (left) and αMNs  (right). However, comparing WT and En1-Het shows a significant difference only at 3 months and not later. Unpaired two-sided t-test. (*p<0.05; **p<0.005; ***p<0.0005, ****p<0.0001). Data information: this experiment was done once. Values are mean ± SD. Between 151 and 1215 neurons  and 3 to 5 mice were analyzed for each condition.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "A. Left panel: Injection and analysis protocol. Right panel: muscle strength analysis demonstrating that hEN1 injection at 1 month prevents muscular strength decrease observed in 3-month-old En1-Het mice. One-way ANOVA followed by two-sided t-test. (*p<0.05, ****p<0.0001). N=6-10. Data information: This experiment was performed once. Values are mean ± SD.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "B. Left panel: Increased p62/SQTSM1 staining  in 3-month-old ChAT+ MNs  from control En1-Het is abolished by hEN1 injection at 1 month. Right panel: quantification of p62/SQTSM1 staining  in γMNs  and αMNs  of control and hEN1-injected 3-month-old En1-het mice. One-way ANOVA followed by two-sided t-test. (**p<0.01, ****p<0.0001). Between XXX neurons  in YY mice  were analyzed in this experiment. Data information: This experiment was performed once. Values are mean ± SD. Between 111 and 303 neurons  and 4-5 mice  were analyzed for each condition.",
    "ncbi_link": "En1: 13798"
  },
  {
    "caption": "(A) HeLa cells were treated with control or indicated siRNA for 72 hours and SL biosynthesis measured by [3H] - sphingosine pulse-chase assay. GSL levels are expressed as fold changes with respect to control. CERT and FAPP2 knockdowns (blue bars) were used as controls.",
    "ncbi_link": "CERT: 10087
FAPP2: 84725"
  },
  {
    "caption": "(D) Control and GRASP55KO cells were processed for Cy3-conjugated Shiga Toxin (ShTxB) and Alexa488-conjugated Cholera Toxin (ChTxB) staining followed by flow cytometry analysis. Mean fluorescence intensity was measured and represented.",
    "ncbi_link": "GRASP55: 26003"
  },
  {
    "caption": "(C) Control and GRASP55 KO cells were transfected for 16 hours with GCS-HA or LCS-HA and processed for cryoimmunolabeling with anti-HA antibody (10-nm gold particles) and anti-GM130 antibody (15-nm gold particles) in case of GCS-HA and anti-HA antibody (15-nm gold particles) and anti-GM130 antibody (10-nm gold particles) in case of LCS-HA. Representative images of the distribution of GCS-HA and LCS-HA are shown. Scale bar 200nm. Red asterisk marks C4 cisterna and blue circles indicate GM130 labelling.",
    "ncbi_link": "GRASP55: 26003"
  },
  {
    "caption": "(A-C) Control and GRASP55 KO (#2) cells were transfected for 16 hours with the indicated HA-tagged enzymes and processed for cryo-immunolabeling with anti-HA antibody (10-nm gold particles) and anti-GM130 antibody (15-nm gold particles). Representative images of the distribution of HA-tagged enzymes are shown. Red circles indicate GM130 labelling. Arrow heads represent the peri-Golgi vesicles. Scale bar 150 nm. Quantification of the distribution of enzymes in vesicles represented as normalized linear density",
    "ncbi_link": "GRASP55: 26003"
  },
  {
    "caption": "(A Control and GRASP55 KO clones were pre-treated with DMSO or BFA (5μg/ml) for 30 min and SL output monitored by [3H] - sphingosine pulse-chase assay (8 h chase). Total GSL levels were quantified and expressed as fold changes with respect to control (A).",
    "ncbi_link": "GRASP55: 26003"
  },
  {
    "caption": "B) Control and GRASP55 KO clones were pre-treated with DMSO or BFA (5μg/ml) for 30 min and SL output monitored by [3H] - sphingosine pulse-chase assay (8 h chase). The GM/Gb ratio was calculated and represented (B).",
    "ncbi_link": "GRASP55: 26003"
  },
  {
    "caption": "(F) CERT was silenced using siRNAs for 72 hours in control and GRASP55 KO (#2) clone before subjecting to [3H] -sphingosine pulse chase assay. GSLs were quantified and represented as fold change with respect to control.",
    "ncbi_link": "CERT: 10087
GRASP55: 26003"
  },
  {
    "caption": " t-SNE maps highlighting the expression of SARS-CoV-2 entry receptors ACE2 Transcript counts are given in a Log2 scale. ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " O) t-SNE maps highlighting the expression of SARS-CoV-2 entry receptors TMPRSS2 Transcript counts are given in a Log2 scale. ",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": " (G)  CHO-K1 Tet-On cells expressing  Z α1-antitrypsin were induced with  doxycycline (0.5μg/ml) for 48 h. Cells were incubated with 10μM GSK716  (or 0.1% v/v DMSO for the control) during the induction. Culture media containing either the experimental compound or DMSO  were changed every 24 h. After the induction, cells were labelled for 10 minutes with 35S Met/Cys and chased at the indicated times. Culture media were collected and cells lysed in 1% v/v NP-40 buffer. Intracellular fractions and culture media from cells expressing Z α1-antitrypsin  were immunoprecipitated either with a mAb against total α1-antitrypsin  (3C11) or with a polymer-specific mAb (2C1). Samples were resolved by 4-12% w/v acrylamide SDS-PAGE  and detected by autoradiography. (H) The graphs show the effect of GSK716 on intracellular and extracellular Z α1-antitrypsin (mean±SEM, n=2) ",
    "ncbi_link": "Z α1-antitrypsin: 5265"
  },
  {
    "caption": "Representative calcium signature enriched in P-EMT tumors (comparing ECAD- vs. ECAD+ tumor cells). NES, nominal P-value, and FDR are shown. Statistical analysis performed in GSEA.",
    "ncbi_link": "ECAD: 12550"
  },
  {
    "caption": "Representative image of tumor cells transduced with GCaMP6 (Left). Yellow arrows (mesenchymal cells), red arrows (epithelial cells), scale bar = 50μm. GCaMP6 mean fluorescent intensity (MFI) in ECADHIGH or ECADLOW cells cultured in indicated medium (0 Ca2+ or 2 Ca2+) for 1h (Right). Representative of 3 independent murine PDA cell lines run in triplicate. Statistical analysis by Student's unpaired t-test (*, p<0.05; non-significant (NS); ±SD).",
    "ncbi_link": "ECAD: 12550"
  },
  {
    "caption": "Flow cytometry analysis of ECADHIGH or ECADLOW cells loaded with Indo-1 and cultured in indicated medium (0 Ca2+ or 2 Ca2+) for 1h. Representative of 2 independent cell lines (n indicates the number of cells analyzed in each group, ECADHIGH 0 Ca2+ n=4963, ECADLOW 0 Ca2+ n=14, ECADHIGH 2 Ca2+ n=6575, ECADLOW 2 Ca2+ n=29). Representative of 2 independent murine PDA cell lines run in triplicate. Statistical analysis by Student's unpaired t-test (****, p<0.0001; non-significant (NS); ±SD).",
    "ncbi_link": "ECAD: 12550"
  },
  {
    "caption": "Top: Relative mRNA expression of Ecad after treatment with 2.5μM ionomycin or 10ng/ml TGFβ for denoted time. Bottom: Western blot analysis of total E-cadherin and Vimentin protein for denoted time. Experiment was run in duplicate with three different murine PDA cell lines. Statistical analysis by ANOVA (***, p<0.001; non-significant (NS); ±SEM).",
    "ncbi_link": "Ecad: 12550"
  },
  {
    "caption": "MFI of surface E-cadherin in CnB knockout lines after 48h treatment with DMSO, 2.5μM ionomycin, or 10ng/ml TGFβ. Experiment was repeated in two different murine PDA cell lines in triplicate. Statistical analysis by ANOVA (***, p<0.001; ****, p<0.00001; ±SD).",
    "ncbi_link": "CnB: 19058"
  },
  {
    "caption": "MFI of surface E-cadherin of shRNA non-targeting (shNT) (Left) or shCAMK2B (Right) after 48h treatment with DMSO, 2.5μM ionomycin, or 10ng/ml TGFβ. Experiment was repeated in two different murine PDA cell lines. Statistical analysis by ANOVA (***, p<0.001; ****, p<0.00001; ±SD).",
    "ncbi_link": "CAMK2B: 12323"
  },
  {
    "caption": "A-C ARR1/10/12 protein levels were examined by western blot when five-day-old seedlings of 35S:ARR1:MYC, 35S:ARR10:YFP, and 35S:ARR12:YFP were treated with or without 200 mM NaCl for the indicated time points. Actin was used as the internal reference. The relative intensity of band detected by anti-MYC or anti-GFP antibody to that by anti-Actin antibody without treatment was set to 1.0. D-F Quantification analysis of the protein levels of ARR1/10/12 in (A-C). ",
    "ncbi_link": "MYC: 
YFP: "
  },
  {
    "caption": "C In vivo Coimmunoprecipitation assay of MPK3/4/6 and ARR1/10/12. MPK3/4/6-YFP and ARR1/10/12-MYC were co-expressed in Arabidopsis protoplast cells. Protein extracts (Input) were immunoprecipitated with GFP Trap magnetic agarose beads. Immunoblots were performed with anti-MYC antibody to detect ARR1/10/12 and with anti-GFP antibody to detect MPK3/4/6.",
    "ncbi_link": "MYC: 
YFP: 
MPK3: 823706
ARR1: 820940"
  },
  {
    "caption": "A-C Immunoblot analysis the effects of MPK3/6 on salt stress-induced ARR1/10/12 protein degradation. Seven-day-old seedlings of 35S:ARR1:MYC, 35S:ARR10:YFP, and 35S:ARR12:YFP in Col-0 and MPK3SR backgrounds were treated with or without 200 mM NaCl for indicated time points. Actin was used as the internal reference. The relative intensity of band detected by anti-MYC or anti-GFP antibody to that by anti-Actin antibody without treatment was set to 1.0. D-I Quantification analysis of MPK3/6 effect on salt stress-induced ARR1/10/12 protein degradation in (A-C). ",
    "ncbi_link": "MPK3: 823706"
  },
  {
    "caption": "A-C Immunoblot analysis stability of ARR1/10/12 and ARR1T553A/10S383A/12S323A proteins under salt stress. Seven-day-old seedlings of 35S:ARR1:MYC, 35S:ARR10:YFP, 35S:ARR12:YFP, 35S:ARR1T553A:MYC, 35S:ARR10S383A:YFP, and 35S:ARR12S323A:YFP were treated with or without 200 mM NaCl for indicated time points. Actin was used as the internal reference. The relative intensity of band detected by anti-MYC or anti-GFP antibody to that by anti-Actin antibody without treatment was set to 1.0. D-I Quantification analysis of stability of ARR1/10/12 and ARR1T553A/10S383A/12S323A proteins under salt stress in (A-C). ",
    "ncbi_link": "MYC: 
YFP: 
ARR1: 820940
ARR10: 829322
ARR12: 817056"
  },
  {
    "caption": "Four-day-old seedlings of 35S:ARR1:MYC, 35S:ARR1T553A:MYC, and 35S:ARR1T553D:MYC were transferred to 1/2 MS medium supplemented with or without 50 mM or 75 mM NaCl. After three days of salt treatment, plant phenotypes (A) were determined.",
    "ncbi_link": "MYC: 
ARR1: 820940"
  },
  {
    "caption": "Four-day-old seedlings of 35S:ARR10:YFP, 35S:ARR10S383A:YFP, and 35S:ARR10S383D:YFP were transferred to 1/2 MS medium supplemented with or without 50 mM or 75 mM NaCl. After three days of salt treatment, plant phenotypes (A) were determined.",
    "ncbi_link": "YFP: 
ARR10: 829322"
  },
  {
    "caption": "Four-day-old seedlings of 35S:ARR12:YFP, 35S:ARR12S323A:YFP, and 35S:ARR12S323D:YFP were transferred to 1/2 MS medium supplemented with or without 50 mM or 75 mM NaCl. After three days of salt treatment, plant phenotypes were determined.",
    "ncbi_link": "YFP: 
ARR12: 817056"
  },
  {
    "caption": "Three-day-old seedlings of Col-0, MPK3SR, MPK3SRarr1/12, and arr1/12 were transferred to 0.5 μM NA-PP1-containing 1/2 MS medium for 2 d to inhibit MPK3TG in MPK3SR and MPK3SRarr1/12 and then the plants were transferred to 0.2 μM NA-PP1-containing 1/2 MS medium supplemented with or without 50 mM or 75 mM NaCl. Pictures were taken and the elongated root length was determined 3 d later",
    "ncbi_link": "MPK3: 823706
arr1: 820940"
  },
  {
    "caption": "A: Morphology  (PAS staining, upper panels) and quantification of glomerular lesions (lower panel) of kidneys from 28-month-old p16 INK-ATTAC mice treated with either vehicle (AP-) or AP20187 (AP+). Original magnification X400. Scale bar = 20 μm. n = 5. B: WT1 immunostaining  (upper panels) and quantification of WT1-positive glomerular cells  (lower panel) in 28-month-old p16 INK-ATTAC mice treated with either vehicle (AP-) or AP20187 (AP+). Original magnification X400. Scale bar = 20 μm. n = 5. C: PAI-1 immunostaining  (upper panels) and quantification of PAI-1-positive glomeruli (lower panel) in 28-month-old  p16 INK-ATTAC mice treated with either vehicle (AP-) or AP20187 (AP+). Original magnification X400. Scale bar = 20 μm. n = 5. Data information: Data are means ± SEM. Statistical analysis: t-student test: AP+ versus AP- mice.",
    "ncbi_link": "p16 INK: 12578"
  },
  {
    "caption": "A: PAI-1 immunohistochemistry  (upper panels) and quantification of PAI-1-positive glomeruli (lower panel) in kidneys  of PAI-1flox and PAI-1∆endo mice at 22 months of age. Original magnification X400. Scale bar = 20 μm. n = 4 for PAI-1flox and PAI-1∆endo mice, respectively. B: Morphology  (PAS staining, upper panels) and quantification of glomerular lesions (lower panel) of  kidneys from PAI-1flox and PAI-1∆endo mice at 22 months of age. Original magnification X400. Scale bar = 20 μm. n = 12 for  PAI-1flox and PAI-1∆endo mice, respectively. C: TUNEL assay (upper panels) and quantification of TUNEL-positive glomeruli (lower panel) in kidneys from PAI-1flox and PAI-1∆endo mice at 22 months of age. Original magnification X400. Scale bar = 20 μm. n = 6 for PAI-1flox and PAI-1∆endo mice, respectively. D: WT1 immunostaining  (upper panels) and quantification of WT1-positive  glomerular cells  (lower panel) in kidneys from  PAI-1flox and PAI-1∆endo mice at 22 months of age. Original magnification X400. Scale bar = 20 μm. n = 4 and n = 6 for PAI-1flox and PAI-1∆endo mice, respectively. Data information: Data are means ± SEM. Statistical analysis: t-student test: PAI-1∆endo versus  PAI-1flox mice.",
    "ncbi_link": "PAI-1: 18787"
  },
  {
    "caption": "G: p21/griffonia simplicifolia/nephrin coimmunostaining in kidneys (upper panels) from  PAI-1flox and PAI-1∆endo mice at 22 months of age and quantification (lower panel) of p21-positive endothelial cells per  glomeruli. Original magnification X630. Scale bar = 10 μm. n = 4 and n = 6 for PAI-1flox and PAI-1∆endo mice, respectively. H: 53BP1/CD34 coimmunostaining (upper panels) and quantification of glomerular 53BP1 foci in  glomerular endothelial cells  from PAI-1flox and PAI-1∆endo mice  at 22 months of age. Original magnification X630. Scale bar = 10 μm. n=4 and n=6 for PAI-1flox and PAI-1∆endo mice, respectively. Arrows show 53BP1 positive foci. Data information: Data are means ± SEM. Statistical analysis: t-student test: PAI-1∆endo versus  PAI-1flox mice.",
    "ncbi_link": "PAI-1: 18787"
  },
  {
    "caption": "C: Relative mRNA expression  of senescence markers (p16  and  p21) and SASP molecules (PAI-1, IL6,  IL8) in GEnC at early (p9) or late (p17) passage. n = 5 independent experiments. Data information: Data are means ± SEM. Statistical analysis: t-student test",
    "ncbi_link": "p21: 1026
p16: 1029
IL8: 3576
IL6: 3569
PAI-1: 26135"
  },
  {
    "caption": "D. Representative genotyping  of the c.1192C>A mutation by allele-specific PCR. For each sample, two PCRs  were performed, one with a specific primer for the 1192C allele (PCR  1) and a second with specific primers for the 1192A allele (PCR  2). An 821-bp band indicated the presence of the allele; amplification failure indicated the absence of the allele. The 434 bp amplification product of the hGH control primer is presented in all lanes. In the gel, the first lane (MW) shows the 100 bp DNA ladder marker ; for the other lanes, C and A indicate the product from PCR  1 and PCR  2, respectively, amplified from RIF+/+ (1(CC)), RIF+/- (2(CA)) and RIF-/- (3(AA)) samples.",
    "ncbi_link": "GH: 2688"
  },
  {
    "caption": "B. Western blotting shows that the anti-RIF  and anti-VER  antibodies bind  to HuSLC44A2. Western blots  of whole Sf9  lysates (WCL) expressing full-length recombinant human SLC44A2  cDNA (rHuSLC44A2) were probed with RIF  and VER  antisera (1:10). Lanes 1 and 2 show strong binding  to rHuSLC44A2. Titer differences in the sera required longer exposure (10 min) of the filter to the film to develop the image with VER  serum compared to only 30 second exposure for RIF  serum. A similar blot  of immunoprecipitated  rHuSLC44A2  from the Sf9  lysates similarly reacted with RIF  and VER  sera (lanes 3 and 4) showed equivalent exposure times (30 seconds for both sera) when tested against the concentrated rHuSLC44A2 protein.",
    "ncbi_link": "SLC44A2: 57153"
  },
  {
    "caption": "D. Western blot  of murine Slc44a2  protein immunoprecipitated  from wild-type and Slc44a2  knockout mice  with rabbit anti CTL2-NT serum was probed with anti CTL2-NT (left panel) and with VER  serum (center Panel) or RIF  serum (right panel). The left panel was developed with goat anti rabbit IgG heavy and light chain ; the center and right panels were developed with rabbit anti human IgG and IgM heavy and light chain specific",
    "ncbi_link": "Slc44a2: 68682"
  },
  {
    "caption": "A. Terminal differentiation  of HSPCs  from healthy control and SLC44A2null proband was monitored via α4-integrin and band 3 levels of GPApos cells at day 6 after EPO  addition.",
    "ncbi_link": "SLC44A2: 57153"
  },
  {
    "caption": "A. SLC44A2  transcript variants P1 and P2 were amplified from cDNA samples isolated from control reticulocytes  (CTRL RETIC), neutrophils  (CTRL NEUTRO), and PBMC  of the VER- proband 2 (VER PBMC). The purity of reticulocytes  and neutrophils  was verified by flow cytometry using anti-CD71  and anti-CD16  antibodies, respectively.",
    "ncbi_link": "SLC44A2: 57153"
  },
  {
    "caption": "(A-H) Live wildtype littermate and Slc7a5-null embryos imaged shortly after dissection. (A-D) Wildtype and (E-H) Slc7a5-null E9.75 embryos from lateral (A, D, E, H), frontal (B, F) or dorsal (C, G) views; (e1-h1) higher magnification images of the Slc7a5-null embryo. White arrowheads indicate the smaller limb bud (compare B and F), open/reduced forebrain (compare D and H), open neural tube at posterior (compare C and E, e1) and anterior (compare B and F, f1) regions. Black arrowheads indicate kinked neural tube (compare C and G, g1) and apparently missing optic and smaller otic vesicles (ov) (compare D and h1). Data information: Scale bars 200 µm",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "mRNA in situ hybridization and immunofluorescence in E9.5 or E10.5 wildtype and Slc7a5-null embryos for key marker genes. (I-L) Fgf8 mRNA transcripts were detected in wildtype (I-j1) and in Slc7a5-null (K-l1) E10.5 embryos (n=4 each) (white arrowheads indicate limb buds in K and the isthmus in L) with (j1, l1) sections through isthmus at midbrain/hindbrain border and (i1, k1) lateral views of forelimb buds. Data information: Scale bars 200 µm, except sections 100 µm.",
    "ncbi_link": "Fgf8: 14179
Slc7a5: 20539"
  },
  {
    "caption": "mRNA in situ hybridization and immunofluorescence in E9.5 or E10.5 wildtype and Slc7a5-null embryos for key marker genes. (M-N) Wholemount Tubulin-β-III (Tuj1) immunofluorescence performed on (M, m1) wildtype and (N, n1) Slc7a5-null E9.5-E10.5 embryos (n=5 each condition). Dorsal root ganglia (DRG) and Sympathetic Chain Ganglia (SCG) are indicated with open arrowheads together with cranial ganglia IX, X and XI. Images in (m1, n1) show higher magnification of the cranial ganglia V, VII/VIII (open arrowheads). Data information: Scale bars 200 µm",
    "ncbi_link": "Slc7a5: 20539
Tubulin-β-III: 22152"
  },
  {
    "caption": "mRNA in situ hybridization and immunofluorescence in E9.5 or E10.5 wildtype and Slc7a5-null embryos for key marker genes. (O-P) Neurog2 expression in wildtype (O-o4) and Slc7a5-null embryos (P-p4) (n= 5 and n=6 each), showing reduced expression in forebrain (o2, p2), cranial ganglia (o1, o3, p1, p3, arrowheads) and in spinal cord at level of forelimb (o4, p4, arrowheads indicate position of neural crest). Data information: Scale bars 200 µm, except sections 100 µm.",
    "ncbi_link": "Neurog2: 11924
Slc7a5: 20539"
  },
  {
    "caption": "(A-B) Sox10 in situ hybridization in (A) wildtype and (B) Slc7a5-null E9.5 embryos (n=4 each) with TSs of (a1, b1) the hindbrain at level of trigeminal ganglion V, (a2, b2) otic vesicles and the neural tube at more posterior levels (a3, a4, b3, b4). Scale bars 200 µm, except sections a1 - b4, 100 µm. Closed white arrowheads in (a3, a4) indicate neural crest, open white arrowheads indicate depleted neural crest in (b3) and position where neural crest should be in (b4).",
    "ncbi_link": "Slc7a5: 20539
Sox10: 20665"
  },
  {
    "caption": "(C-G) Immunofluorescence on TSs caudal spinal cord of E9.5 wildtype littermates and Slc7a5-null embryos; Pax3 and FoxA2 were used as indicators for dorso-ventral organisation in (C, F) wildtype, n=2 (for FoxA2) and n= 4 (For Pax3) and (D, G) Slc7a5-null, n=3 (for FoxA2 ) and n = 3 for Pax3) neural tube. Arrowheads indicate border of Pax3 expression domain. Scale bars 50 µm. (E) Percentage of Pax3 expressing cells was determined by counting these cells and all DAPI labelled nuclei in the neural tube and comparison made between wildtype (4 embryos, 6 sections each) and Slc7a5-null (3 embryos, 6 sections each), each dot represents the average for one embryo, unpaired t-test, *p = 0.018 (see original source data). Error bars indicate SEM. ",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(A-D) Proliferation was assessed in the spinal cord (forelimb level) (A, B) using a phospho-Histone3 (phospho-H3) antibody (green) to identify mitotic cells and DAPI (blue) to label nuclei; cells were counted in 3 wildtype (18 sections) and 3 Slc7a5-null embryos (18 sections) and mitotic index calculated; (C, D) Proliferation was also assessed in the forebrain in 3 wildtype embryos (17 sections) and 3 Slc7a5-null embryos (16 sections). White dashed lines indicate midline. Data information All scale bars 50 µm.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(E, F) Comparison of mitotic index in wildtype and Slc7a5-null (E) spinal cord, p = 0.872 ,and (F) forebrain *p = 0.049, each dot represents the average for one embryo, unpaired t-test Data information: *p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(I) Labelling intensity was measured and plotted relative to DAPI intensity; 6 wildtype embryos (18 sections) and 5 Slc7a5-null embryos (19 sections). Each dot represents the average for one embryo, (*p = 0.0457) unpaired t-test with Welch correction Data information: *p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(J) Western blot of individual E9.5 wildtype (n=3) and Slc7a5-null (n=4) embryo lysates immunoblotted using an antibody against phospho-S6K (Thr389) and total P70S6K for loading control. Band intensities were measured with FIJI and an unpaired t-test was performed for statistical analysis Data information: *p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(K-L) (K) Validation by qPCR of the targets identified by RNAseq; qPCR was performed on individual E8.5 embryos of each genotype (wildtype n=5, heterozygous n=9 and Slc7a5-null n=7). (L) qPCR was performed on individual E9.5 embryos (wildtype n=5, heterozygous n=3 and Slc7a5-null n=4) using primers specific for genes associated with the integrated stress response. A one-way Anova test with a Turkey post-test was performed. Data information: *p<0.05, **p<0.01, ***p<0.001 Error bars indicate SEM.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "mRNA in situ hybridization was performed at E9.5 to detect Chac1 in (A-a6) wildtype and (B-b6) Slc7a5-null littermate embryos (n=3 for each condition); Chac1 expression at E10 in emerging limb buds assessed in (C) wildtype and (D) Slc7a5-null littermate embryos (n=2 for each condition) Scale bars 200 µm for whole embryo images and 100 µm for sections.",
    "ncbi_link": "Chac1: 69065
Slc7a5: 20539"
  },
  {
    "caption": "mRNA in situ hybridization was performed at E9.5 to detect Trib3 mRNA detected in (E-e6) wildtype and (F-f6) Slc7a5-null littermate embryos (n=3 for each condition) and in emerging limb buds at E10.5 assessed in (G) wildtype and (H) Slc7a5-null littermate embryos (n=2 for each condition). Scale bars 200 µm for whole embryo images and 100 µm for sections.",
    "ncbi_link": "Slc7a5: 20539
Trib3: 228775"
  },
  {
    "caption": "mRNA in situ hybridization was performed at E9.5 Chac1 and Trib3 transcripts were also detected in wildtype E9.5 embryos after >3 days in situ hybridisation reaction (n=3 and n=6 respectively). Lateral view (I and K), optic vesicles (white arrowheads), branchial arches (ba) and otic vesicles (ov). Dorsal view (J and L), neural tube (nt) and limb buds (white arrowheads). Scale bars 200 µm for whole embryo images and 100 µm for sections.",
    "ncbi_link": "Chac1: 69065
Trib3: 228775"
  },
  {
    "caption": "Western blot of individual E9.5 wildtype (n=4) and Slc7a5-null (n=4) embryo lysates immunoblotted using an antibody against phospho-GCN2 (Thr899) and total GCN2 (loading control), ***p = 0.0001 ; band intensities measured with FIJI and analysed with unpaired t-test Data information: All error bars indicate SEM.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "Western blot of individual E9.5 wildtype (n=4) and Slc7a5-null (n=4) embryo lysates immunoblotted using an antibody against phospho-eIF2α (Ser51) and total eIFα (loading control), *p = 0.0482, band intensities measured with FIJI and analysed with unpaired t-test Data information: All error bars indicate SEM.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(C-F) phosphorylated eIFα was assessed by immunofluorescence in E9.5 embryos in the forebrain, wildtype (C,c1) (n=2 embryos, 0/14 sections) and Slc7a5-null (D, d1) (n=2 embryos 16/16 sections), and in hindbrain/anterior spinal cord, wildtype (E-e2) (n= 4 embryos, 0/62 sections) and Slc7a5-null (F-f2) (n= 4 embryos, 54/54 sections) including in the otic vesicle (compare e2, f2). Scale bars in (C-e1, D-f1) 100 µm and in (e2 and f2) 25µm. Arrowheads indicate ventral midline.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(G) An increase in Trib3 protein was detected by Western blot in Slc7a5-null embryos, each lane represents an E9.5 embryo lysate (wildtype n=3, Slc7a5-null, n=4) with α-Tubulin loading control, unpaired t-test *p = 0.0153 Data information: All error bars indicate SEM.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(H-L) TUNEL assay to detect apoptotic cells in wildtype (n=3 embryos, 32 sections) or Slc7a5-null (n=5 embryos, 47 sections); (H, I) transverse sections through the head at level of the forebrain and (J, K) the spinal cord, (H-K) scale bars 50 µm, arrowheads indicate ventral midline. (L) Quantification of TUNEL positive cells within spinal cord sections was performed Each dot represents the average apoptosis cell count for a single embryo, Welch's correction unpaired t-test, p = 0.250, F-test to compare variances, p = 0.0003 Data information: All error bars indicate SEM.",
    "ncbi_link": "Slc7a5: 20539"
  },
  {
    "caption": "(A-B) (A,a1) Wnt β-catenin target Axin2 strongly expressed in littermate, (a2, a3) in TS, and (B, b1) in Scl7a5-null embryos (b2, b3) in TS (n=2 littermates, n=6/6 Slc7a5-null embryos). Data information: White dashed lines indicate position of sections. Scale bars 200 µm",
    "ncbi_link": "Slc7a5: 20539
Scl7a5: 20539"
  },
  {
    "caption": "(C, d1) Axin2 transcripts in embryo trunk explant exposed to DMSO (C, c1, n=12/12) were reduced in Wnt-c59 exposed explants (D, d1, n=14/14). Images in (c1, d1) show TS through explants (data from 3 independent embryo explant experiments). (E, F) Slc7a5 transcripts in embryo trunk explant exposed to DMSO (E, e1, n=9/10) or Wnt-c59 (F, f1, n=15/15). Images in (e1, f1) show TS through explants (data from 3 independent embryo explant experiments). Data information: Scale bars = 100 µm",
    "ncbi_link": "Axin2: 12006
Slc7a5: 20539"
  },
  {
    "caption": "(G, H) Slc7a5 expression in control T-Cre;Ctnnb1flLOF/Δ heterozygous littermate embryo (G, g1) and in TS (g2, g3), and in T-Cre;Ctnnb1flLOF/Δ mutant embryo where Slc7a5 transcripts are absent in posterior neural tube (the region of T-cre recombination, indicated with white arrowhead in H) and shown in TS in (h2, h3) (n= 0/6 littermate and n=6/6 mutant embryos). Data information: White dashed lines indicate position of sections. Scale bars, 200 µm",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Ctnnb1: 12387
Slc7a5: 20539"
  },
  {
    "caption": "(I, J) Trib3 is lacking in T-Cre;Ctnnb1flLOF/Δ heterozygous control embryos at E7.75 (I), caudal region dissected from the same embryo (white dashed box in I) (i1) and viewed in TS (i2); Trib3 detected in homozygous T-Cre;Ctnnb1flLOF/Δ embryo (J), in caudal region dissected from the same embryo (white dashed box in J) (j1) and shown in TS in caudal epiblast and remnant primitive streak (ps) (j2) (n= 3/3 T-Cre;Ctnnb1flLOF/Δ embryos and 14 littermate controls). Trib3 was also detected in the more rostral forming neural tube at this early stage (seen in J) and so in cells not directly experiencing β-catenin loss; this may reflect the failure to form paraxial mesoderm, which provides signals that promote and support neurogenesis. Data information: White dashed lines indicate position of sections. Scale bars all sections 50 µm.",
    "ncbi_link": "Cre: 2777477
Ctnnb1: 12387
β-catenin: 12387
Trib3: 228775"
  },
  {
    "caption": "(K-M) At E9.5 Trib3 was not detected in T-Cre;Ctnnb1flLOF/Δ heterozygous littermate embryos (K, k1) and in TS ( k2, k3), but was detected in homozygous T-Cre;Ctnnb1flLOF/Δ mutant embryos (L-m3) in patches of cells in neural tube (nt) (L - l2), gut (g) (l3) and somites (s) (m2, arrowheads) (n=9/9 T-Cre;Ctnnb1flLOF/Δ embryos and 12 littermate controls). Data information: White dashed lines indicate position of sections. Scale bars, all sections 50 µm.",
    "ncbi_link": "Cre: 2777477
Ctnnb1: 12387
Trib3: 228775"
  },
  {
    "caption": "(B) Immunoblot analysis of whole cell samples of the HA-tagged full-length (FL) IFT54, and its deletion mutants as indicated, each expressed in the ift54 null mutant; wild type (WT) and ift54 mutant cells were used as control. Anti-HA was use to visualize the transgenic proteins, antibodies to FLA8/KIF3B were used as a loading control.",
    "ncbi_link": "HA: 
IFT54: 5725022
ift54: 5725022"
  },
  {
    "caption": "(C) Histogram showing ciliary length distribution in populations of ift54 mutant cells transformed with the deletion mutant constructs as indicated. Wild type (WT) cells were used as a control.",
    "ncbi_link": "ift54: 5725022"
  },
  {
    "caption": "(D) Representative DIC images of wild type (WT), ift54 and ift54 cells transformed with the deletion constructs as indicated. Arrows indicate cilia bulges. Scale bar, 5 μm.",
    "ncbi_link": "ift54: 5725022"
  },
  {
    "caption": "(B, C) Immunostaining analysis of IFT43 and IFT38 in the deletion mutants as indicated. Cells were fixed and stained with antibodies against IFT43 (an IFT-A subunit) (B) or against IFT38 (an IFT-B subunit) (C) followed by imaging using both DIC and epifluorescence microscopy. IFT43 and IFT38 accumulated at the ciliary tip in IFT54Δ261-275 mutant but at proximal end of cilia in IFT54Δ342-356 mutant. Arrows indicate ciliary bulges. WT, wild-type cells. Scale bars, 5 μm.",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(A) Immunostaining of cells with antibody against IFT dynein subunit D1bLIC. D1bLIC is absent in the cilia bulges at the ciliary tip in IFT54Δ261-275 mutant while enriched at the cilia bulges at proximal end of cilia in IFT54Δ342-356 mutant. WT, wild type cells. Arrows indicate ciliary bulges. Scale bar, 5 μm. (B) Immunostaining of cells with antibody against kinesin-II subunit FLA10. FLA10 is enriched in cilia bulges at the ciliary tip in IFT54Δ261-275 mutant or at proximal end of cilia in IFT54Δ342-356 mutant. WT, wild type cells. The insets show enhanced and/or enlarged images. Arrows indicate ciliary bulges. Scale bar, 5 μm. ",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(C, D) Immunoblot analysis of whole cells (C) and isolated cilia (D) of wild type and the three IFT54 deletion mutants. The membranes were probed with antibodies against IFT complex and motor proteins as indicated. Wild-type levels of the various IFT components were detected in the whole cell samples of the deletion strains (C). IFT121, IFT38 and FLA8 accumulated in cilia of both IFT54Δ261-275 and IFT54Δ342-356 mutants. D1bLIC was relatively reduced in IFT54Δ261-275 mutant cilia but was substantially increased in IFT54Δ342-356 mutant cilia (D). Ratios of protein amounts from one representative experiment are in parentheses.",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(A) Kymograms showing the trajectories of IFT trains inside cilia as visualized with IFT43-YFP. An ift43 rescue strain expressing IFT43-YFP (as a control) and the IFT54Δ342-356 mutant expressing IFT43-YFP were analyzed by live imaging via TIRF microscopy.",
    "ncbi_link": "IFT54: 5725022
ift43: 5722198"
  },
  {
    "caption": "(B-C) Velocities (B) and frequencies (C) of anterograde and retrograde IFT of IFT43-YFP in control and the IFT54Δ342-356 mutant. n represents the number of cilia assayed from three independent experiments. Values show the mean ± S.D. Unpaired two-tailed Student's t test analysis, ***, p<0.0001.",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(D) Deletion of residues 342-356 of IFT54 increases its interaction with kinesin-II. Cell extracts from wild type (WT), ift54 expressing HA-tagged full-length (FL) IFT54 or IFT54Δ342-356 mutant were subjected to immunoprecipitation with anti-HA antibody followed by immunoblotting with the indicated antibodies. The normalized ratios of FLA8 and FLA10 in the immunoprecipitates (IFT54 versus the mutant) are 1:3.90 and 1:3.13, respectively.",
    "ncbi_link": "HA: 
ift54: 5725022
IFT54: 5725022"
  },
  {
    "caption": "(E) ATP treatment induces dissociation of IFT54 but not IFT54Δ342-356 mutant from kinesin-II. Immunoprecipitation experiments were performed as shown in (D) in the presence or absence of ATP. The normalized ratios of FLA8 and FLA10 in the immunoprecipitates (IFT54 without ATP/with ATP/mutant without ATP/with ATP) are 1:0.37:1.70:1.38 and 1:0.35:1.47:1.45, respectively.",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(A) Kymograms showing the trajectories of IFT trains inside cilia as visualized with D1bLIC-YFP. Wild-type (WT) and IFT54Δ261-275 mutant cells expressing D1bLIC-YFP were analyzed by live imaging via TIRF microscopy.",
    "ncbi_link": "IFT54: 5725022"
  },
  {
    "caption": "(I) Co-immunoprecipitation of IFT54 and IFT54Δ261-275 with D1bLIC. Cell extracts from wild-type (WT), ift54 expressing HA-tagged full-length (FL) IFT54 or IFT54Δ261-275 mutant were subjected to immunoprecipitation with anti-HA antibody followed by immunoblotting with the indicated antibodies. Please note, IFT54Δ261-275 mutant exhibited weaker interaction with D1bLIC relative to the control. The normalized ratio of D1bLIC in the immunoprecipitates (IFT54-HA versus mutant) is 1:0.37.",
    "ncbi_link": "HA: 
ift54: 5725022
IFT54: 5725022"
  },
  {
    "caption": "(J) Interaction of IFT54 with D1bLIC is conserved in mammalian cells. Cell extracts from HEK293T cells expressing eGFP, eGFP tagged TRAF3IP1 or TRAF3IP1Δ460-474 (corresponding deletion mutant of IFT54Δ261-275) were analyzed by immunoprecipitation with GFP antibody followed by immunoblotting with anti-GFP and DYNC2LI1, human homologue of D1bLIC, antibodies, respectively. Please note, the deletion mutant weakened the interaction with IFT dynein subunit DYNC2LI1 relative to the control. The normalized ratio of DYNC2LI1 in the immunoprecipitates (TRAF3IP1 versus mutant) is 1:0.49.",
    "ncbi_link": "eGFP: 
TRAF3IP1: 
IFT54: 5725022"
  },
  {
    "caption": "A, Quantification of Nox4 mRNA levels (A) in cultured rat cardiomyocytes after increasing degrees of serum starvation as compared to serum-replete cells (15% serum). n=4 cell preparations/group.",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "C Cell death after 48 h serum starvation in cardiomyocytes in which Nox4 was depleted by an adenoviral shRNA (Ad.shNox4) as compared to cells infected with a control vector (Ad.Ctl). n=6/group. The representative immunoblot shows reduction in Nox4 protein levels after shRNA-mediated knockdown.",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "G Percentage of Nox4-depleted and control cells with depolarized mitochondria, quantified by flow cytometry. n=3 cell preparations/group (100,000 cells per experiment).",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "J Cell death in serum starved Nox4 knockout MEFs (Nox4KO) and wild-type MEFs (WT). Cat = PEG-catalase (500 U/mL). Nox4KO MEFs were transfected either with active Nox4 or a catalytic inactive Nox4 mutant, Nox4P437H (Mut). n=6-12/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "A Basal mitochondrial calcium levels assessed in serum-starved rat cardiomyocytes using a mitochondrial-targeted cameleon CFP/YFP FRET probe. Nox4 was depleted with silencing RNAs (siRNAs) or cells were transfected with a control scrambled siRNA (siScr). Representative photomicrographs are shown at the top. The spectrum color scale represents the ratio of emitted fluorescence (YFP/CFP). The mean changes in Nox4-depleted cells as compared to scrambled control (dotted line) at the bottom. The representative immunoblot shows depletion of Nox4 protein levels. Scale bars: 10 µm. n=3/group (with >50 cells per individual experiment).",
    "ncbi_link": "CFP: 
YFP: 
Nox4: 85431"
  },
  {
    "caption": "B Basal mitochondrial calcium levels in WT and Nox4KO MEFs after serum starvation. Representative photomicrographs are shown at the top. The spectrum color scale represents the ratio of emitted fluorescence (YFP/CFP). Mean data at the bottom. Scale bars: 10 µm. n=3/group (with >100 cells per individual experiment).",
    "ncbi_link": "CFP: 
YFP: 
Nox4: 50490"
  },
  {
    "caption": "Changes in mitochondrial calcium levels in serum-starved WT and Nox4KO MEFs after the addition of histamine (100 μmol/L, C) n=3/group (with >30 cells per individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "D Changes in mitochondrial calcium levels in serum-starved WT and Nox4KO MEFs after the addition of ATP (100 μmol/L, D). n=3/group (with >30 cells per individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "E, Changes in ER calcium levels measured with an ER-targeted cameleon probe in serum-starved WT and Nox4KO MEFs after the addition of histamine (100 μmol/L, E) n=3/group (with >30 cells per individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "F Changes in ER calcium levels measured with an ER-targeted cameleon probe in serum-starved WT and Nox4KO MEFs after the addition of ATP (100 μmol/L, F). n=3/group (with >30 cells per individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "G Peak increase in mitochondrial calcium levels response in response to histamine (100 μmol/L) in WT MEFs with or without treatment with PEG-catalase (Cat), and in Nox4KO MEFs with or without transfection with active Nox4 or a catalytically inactive Nox4P437H mutant (Mut). n=3/group (with >30 cells per individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "D Electron micrographs showing subcellular localization of Nox4 in wild-type (WT) and Nox4KO mouse hearts, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). hiPSC-CM were depleted of Nox4 using a lentiviral shRNA (Nox4KD) or infected with a control lentivirus. FACL4 was used as a MAM marker. Arrow heads show peri-mitochondrial localization of Nox4 and FACL4, in the proximity of ER cisternae and ribosomes. M=mitochondria, ER=endoplasmic reticulum, T=T-tubule. Scale bars: 100 nm.",
    "ncbi_link": "Nox4: 50490
Nox4: 50507"
  },
  {
    "caption": "A Simplified photomicrographs of proximity ligation studies in WT and Nox4KO MEFs, showing cell borders, nuclei (blue) and yellow dots corresponding to co-localization of proteins. Quantification of the number of dots/cell in each condition is shown to the right. Proximity was tested for the following protein couples: FACL4/Nox4, InsP3R/Nox4, and FACL4/InsP3R. Scale bars: 10 µm. n=3/group (with >30 cells/individual experiment).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "B Simplified photomicrographs of proximity ligation staining in rat cardiomyocytes transfected with Nox4 siRNA or a scrambled control (siScr), with quantification as in (A). Proximity was tested for the FACL4/Nox4 protein couple. Scale bars: 10 µm. n=3/group (with >30 cells/individual experiment).",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "C Simplified photomicrographs of proximity ligation staining in hiPSC-CM (human cardiomyocytes) transduced with Nox4 shRNA or scrambled control, with quantification as in (A). Proximity was tested for the FACL4/Nox4 protein couple. Scale bars: 10 µm. n=3/group (with >30 cells/individual experiment).",
    "ncbi_link": "Nox4: 50507"
  },
  {
    "caption": "C Immunoblotting for phosphorylated and total Akt or InsP3R protein in crude mitochondrial fractions from serum-starved WT and Nox4KO MEFs. FACL4 was used as a loading control for the MAM. InsP3R was first immunopreciptated and then the precipitate was immunoblotted for total InsP3R and for the phosphorylated Akt-substrate motif RXRXX(pS/T) (p-InsP3R). Representative immunoblots are shown at the top and mean data at the bottom. Cat = PEG-catalase. Nox4KO MEFs were transfected either with active Nox4 or a Nox4P437H mutant (Mut). n=3/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "D ROS levels indexed in MEFs using H2O2 specific HyPer probes targeted to the MAM (FACL4 HyPer) or the cytosol (Cyto HyPer). Imaging was performed after serum starvation for 12h. Representative photomicrographs of the fluorescence ratio are shown to the right and mean data for changes in fluorescence ratio presented to the left. The signal obtained using corresponding ROS-insensitive SypHer probes was used to correct for any pH-induced changes in fluorescence; the change in fluorescence ratio between HyPer and corresponding SypHer probe (ΔR) for each condition is reported. n=5 independent cell preparations/group, with at least 20 cells imaged/preparation. Scale bars: 10 µm.",
    "ncbi_link": "HyPer: 
SypHer: "
  },
  {
    "caption": "B Basal mitochondrial calcium levels in serum-starved WT and Nox4KO MEFs in the presence or absence of Akti (1 µmol/L) normalized versus WT MEF control. n=6/group with >20 cells imaged per experiment.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "D Quantification of cell death in serum-starved WT and Nox4KO MEFs in the absence or presence of Akti or XeC. n=6/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "E Cardiac troponin I (cTnI) levels as a marker of cardiomyocyte necrosis in the perfusate of isolated WT and Nox4KO hearts subjected to ischemia-reperfusion (I/R). XeC was added at a final concentration of 2 µmol/L prior to ischemia. n=6-7/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "F Immunoblotting for the phosphorylation levels of Akt and InsP3R in crude mitochondrial fractions from WT and Nox4KO hearts after I/R. InsP3R was first immunopreciptated and then the precipitate was immunoblotted for total InsP3R and for the phosphorylated Akt-substrate motif RXRXX(pS/T) (p-InsP3R). Mean data shown to the right. n=3/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "G Cardiac left ventricular contractile function in isolated Langendorff-perfused WT and Nox4KO hearts at baseline (Basal) and then after I/R. Hearts were treated with XeC (1 μmol/L) or vehicle control for 20 min prior to ischemia. RPP, heart rate x left ventricular pressure product; DEVP, left ventricular developed pressure. n=6-7/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "Confocal images of mPS-PI stained 6-day-old seedlings of Col-0 (A), bravo-2 (B), wox5-1 (C) and bravo-2 wox5-1 (D) mutants. Left black arrows indicate QC cells and right white arrows indicate CSC. Scale bar: 50 µm.",
    "ncbi_link": "bravo-2: 831648
wox5-1: 820297"
  },
  {
    "caption": "Lateral root density (number of lateral roots per mm of root length) of 7-day-olf WT, bravo-2, wox5-1 and bravo-2 wox5-1 mutants (n>40, 2 replicates). Different letters indicate statistically significant differences (p- value < 0.05 Student´s t-test). In the boxplot, box width represents the interquartile range (IQR=Q3-Q1), with the horizontal line denoting the median, while whiskers extend from Q1-1.5IQR to Q3+1.5IQR. White dots are the outliers.  ",
    "ncbi_link": "bravo-2: 831648
wox5-1: 820297"
  },
  {
    "caption": "Confocal images of PI-stained 6-day-old roots. GFP-tagged expression is shown in yellow. A-C) pBRAVO:GFP in WT (A), bravo-2 (B) and wox5-1 (C) knockout backgrounds. D-G) pWOX5:GFP in the WT (D), bravo-2 (E), wox5-1 (F) and bravo-2 wox5-1 (G) knockout backgrounds. Scale bar: 50 µm. Quantification of the GFP fluorescent signal of the roots in A-C (H) and D-G (I). Boxplot indicating the average pixel intensity of the GFP in the stem cell niche (n>25, 3 biological replicates, *p-value < 0.05 Student´s t- test for each genotype versus the WT in the same condition). Quantification was done by integrating the GFP signal in each root across defined areas that included the whole SCN (Appendix Figure S7). In the boxplot, box width represents the interquartile range (IQR=Q3-Q1), with the horizontal line denoting the median, while whiskers extend from Q1-1.5IQR to Q3+1.5IQR. White dots are the outliers and black dots are the experimental observations.",
    "ncbi_link": "bravo-2: 831648
wox5-1: 820297"
  },
  {
    "caption": "Parameter space exploration of (C) the alleviation and the (D) activation models. Boxplots showing the distribution of stationary promoter pBRAVO (pB) and pWOX5 (pW) fold-changes in each mutant and overexpression lines over the WT obtained for different parameter values. Superindexes denote the genotype, standing bravo for bravo mutant, wox5 for wox5 mutant, dm for the bravo wox5 double mutant, Woe for WOX5 overexpression and Boe for BRAVO overexpression. Box width represents the interquartile range (IQR=Q3-Q1), with the horizontal line denoting the median, while whiskers extend from Q1-1.5IQR to Q3+1.5IQR. The results are obtained by solving N=1000 different runs of each model at the stationary state (red and blue stripplots) for the WT, mutants and overexpressor scenarios. These N runs differ in the parameter values, which are chosen at random from a uniform distribution between",
    "ncbi_link": "BRAVO: 831648
bravo: 831648
wox5: 820297
WOX5: 820297"
  },
  {
    "caption": "Expression of the 380 common BRAVO and WOX5 regulated genes from (B). Expression of the 53 genes from (C) showing similar expression in bravo and wox5 mutants. Expression of the 41 genes from (C) showing opposite expression levels in bravo and wox5 mutants.",
    "ncbi_link": "bravo: 831648
BRAVO: 831648
wox5: 820297
WOX5: 820297"
  },
  {
    "caption": "(h) Pulmonary viral titers on days 2 and 7 after infection in Ripk2−/− and WT mice. *P 0.05, **P 0.01, ***P 0.001 (log-rank test (a) and unpaired two-sided Student's t-test (c,d,f,g). Data are pooled from three experiments (a,f-h; mean ± s.e.m. in f-h; n = 10-12 mice total) or are representative of three experiments (b-e; mean ± s.e.m.; n = 3-5 mice per experiment).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(a-c) Supernatants of whole lung homogenates taken on days 2 and 7 after infection of wild-type mice (WT) and Ripk2 −/− mice with the PR8 virus were analyzed for IL-6 and TNF (day 2; a), IL-18 and IFN-γ (b), and indicated chemokines (c). *P 0.05, **P 0.01 (unpaired two-sided Student's t-test). Data were normalized for total protein (t.p.) from lung homogenates. Data are pooled from three experiments (mean ± s.e.m.; n = 10-12 mice total).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(a-c) Analysis on day 2 after infection with PR8 virus of wild-type mice (WT) or Ripk2−/− mice injected intraperitoneally with control rabbit serum and Ripk2−/− mice injected intraperitoneally with anti-IL-18 neutralizing antiserum (αIL-18Ab) 3 h before infection, for IL-18, IFN-γ and CCL2 amounts in whole lung homogenates (a; t.p., total protein), and for neutrophil numbers by immunohistochemistry (b) and by flow cytometry (c). Original magnification, ×20.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(e) Neutrophil numbers in WT, Ripk2−/− and Ripk2−/−Il18−/− mice on day 2 after PR8 infection.",
    "ncbi_link": "Il18: 16173
Ripk2: 192656"
  },
  {
    "caption": "(f) Survival of Ripk2−/−Il18−/−, Ripk2−/− and WT mice. *P 0.05, **P 0.01, ***P 0.001 (one-way ANOVA with Tukey's post-hoc test (a,c,e) and log-rank test (d,f)). Data are representative of two independent experiments (mean ± s.e.m.; n = 6-8 mice per experiment).",
    "ncbi_link": "Il18: 16173
Ripk2: 192656"
  },
  {
    "caption": "(a,b) RIPK2 bone marrow chimeras were analyzed at day 2 after PR8 infection for contribution to elevated IL-18 production by using IL-18 immunohistochemistry (a) and IL-18 ELISA (b) of whole lung homogenates. WT, wild type; t.p., total protein. In a, blue arrows denote IL-18+ macrophages, and red arrows denote IL-18+ bronchial epithelium. Original magnification, ×200.",
    "ncbi_link": "RIPK2: 192656"
  },
  {
    "caption": "(c) Flow cytometry analysis of NK cell counts in Ripk2−/− and wild-type mice.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(d) Analysis of wild-type and Ripk2−/− NK cells for IFN-γ production on a per cell basis.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(f) Analysis of CD8+ T cells for IFN-γ and CD44 expression in wild-type and Ripk2−/− mice. *P 0.05, **P 0.01 (one-way ANOVA with Tukey's post-hoc test (b) and unpaired two-sided Student's t-test (d,f)). Data are representative of two experiments (a,b,f) or three experiments (c-e) (mean ± s.e.m.; n = 6-8 mice per experiment).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(a) Immunoblots showing active caspase-1 (casp-1) p20 compared to GAPDH loading controls in wild-type (WT), Ripk2−/− and Nod2−/− BMDCs after PR8 infection.",
    "ncbi_link": "Nod2: 257632
Ripk2: 192656"
  },
  {
    "caption": "(b) IL-18 release in PR8-infected WT, Ripk2−/− and Nod2−/− BMDCs.",
    "ncbi_link": "Nod2: 257632
Ripk2: 192656"
  },
  {
    "caption": "(e,f) IL-18 and casp-1 activation in Ripk2−/− BMDCs treated with the NLRP3 inflammasome-specific inhibitor glyburide (glyb.) during PR8 infection.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(e,f) IL-18 and casp-1 activation in Ripk2−/− BMDCs treated with the NLRP3 inflammasome-specific inhibitor glyburide (glyb.) during PR8 infection.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(g) Immunoblot analysis of casp-1 p20 during Listeria infection of WT and Aim2−/− BMDCs. *P 0.01, **P 0.001 (one-way ANOVA with Tukey's post-hoc test). Data are representative of six experiments (a,b) or three experiments (c-g) (mean ± s.d.; n = 2-3 replicates per experiment).",
    "ncbi_link": "Aim2: 383619"
  },
  {
    "caption": "(a) Immunoblot analysis of wild-type (WT), Ripk2−/− and Nod2−/− BMDCs for LC3-II (marker for autophagy) after 18 h of PR8 infection.",
    "ncbi_link": "Nod2: 257632
Ripk2: 192656"
  },
  {
    "caption": "(d,e) Immunoblots of LC3-II and caspase-1 (casp-1; e) and IL-18 production (d) in wild-type and Ripk2−/− BMDCs after treatment with rapamycin (Rap).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(f) Immunoblot analysis for LC3-II in lung lysates of PR8-infected wild-type and Ripk2−/− mice (1-5 indicate individual mice).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(g,h) Lungneutrophil infiltration (g) in IAV-infected Ripk2−/− mice treated with rapamycin, Ripk2−/− mice and WT mice (t.p., total protein). *P 0.05, **P 0.01, ***P 0.001 (Mann-Whitney test (b); one-way ANOVA with Tukey's post-hoc test (d,g,h)).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(g,h) IL-18 and IFN-γ amounts (h) in IAV-infected Ripk2−/− mice treated with rapamycin, Ripk2−/− mice and WT mice (t.p., total protein). *P 0.05, **P 0.01, ***P 0.001 (Mann-Whitney test (b); one-way ANOVA with Tukey's post-hoc test (d,g,h)).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(a-c) Flow cytometry analysis of wild-type (WT) and Ripk2−/− BMDCs stained with the mitochondrial superoxide-specific stain MitoSOX during IAV or Listeria infection (a,b) and with the general mitochondrial stain MitoTracker Green during IAV infection (c).",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(a,b) IL-18 amounts (a), and caspase-1 (casp-1) p20 and LC3-II immunoblots (b) in PR8-infected wild-type (WT) BMDCs treated with the p38 and RIPK2 kinase inhibitor SB203580.",
    "ncbi_link": "RIPK2: 192656"
  },
  {
    "caption": "(c) Immunoblots for phosphorylation of ULK1 at Ser555 in WT and Ripk2−/− BMDCs after PR8 infection.",
    "ncbi_link": "Ripk2: 192656"
  },
  {
    "caption": "(d) Immunoblots for casp-1 p20 in untreated or NAC-treated WT and Ulk1−/− BMDCs after PR8 infection.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(e) Flow cytometry analysis of MitoSOX staining in PR8-infected WT and Ulk1−/− BMDCs.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(f) MitoTracker Green staining of PR8-infected WT and Ulk1−/− BMDCs.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "A. cycb1;1, cycb1;2, cycb1;3, cycb1;4, cycb1;1/1;2, cycb1;1/1;3, cycb1;1/1;4, cycb1;2/1;4, cycb1;3/1;4 and the wildtype, from left to right on control plates without genotoxic agent 10 days after germination.B. The wildtype, single and double mutants of cycb1 were grown on control plates without genotoxic agent. Root lengths were measured 10 days after germination.C. The wildtype, cycb1;1, cycb1;2, cycb1;3, cycb1;4, cycb1;1/1;2, cycb1;1/1;3, cycb1;1/1;4, cycb1;2/1;4, cycb1;3/1;4 from left to right on plates containing 1 mM hydroxy urea (HU) 10 days after germination. The rightmost plant is the wee1 mutant that shows high sensitivity to HU.D. The wildtype, single and double mutants of cycb1 were grown on plates supplemented with 1 mM HU. Root lengths were measured 10 days after germination.E. The wildtype, cycb1;1, cycb1;2, cycb1;3, cycb1;4, cycb1;1/1;2, cycb1;1/1;3, cycb1;1/1;4, cycb1;2/1;4, cycb1;3/1;4 from left to right on plates containing 0,6 μg/mL bleomycin (BLM) 10 days after germination. The rightmost plant is the ku70 mutant that shows high sensitivity to BLM.F. The wildtype, single and double mutants of cycb1 were grown on plates supplemented with 0,6 μg/mL BLM. Root lengths were measured 10 days after germination.",
    "ncbi_link": "cycb1;2: 830502
cycb1;1: 829904
cycb1;3: 820325
cycb1;4: 817217"
  },
  {
    "caption": "G. The wildtype, cycb1;1, cycb1;2, cycb1;3, cycb1;4, cycb1;1/1;2, cycb1;1/1;3, cycb1;1/1;4, cycb1;2/1;4, cycb1;3/1;4 from left to right on plates containing 15 μM cisplatin 6 days after germination, i.e. 3 days after transfer from control plates.H. cycb1 mutants were germinated on control plates and were transferred to new control plates three days after germination. Root lengths mutants were measured three days after transfer and the net root growth of three days is shown in the graphs.I. cycb1 single mutants germinated on control plates and were transferred to plates supplemented with 15 μM cisplatin three days after germination. Root lengths of cycb1 mutants were measured three days after transfer and the net root growth of three days is shown in the graphs.J. cycb1 single mutants germinated on control plates and were transferred to plates supplemented with 30 μM cisplatin three days after germination. Root lengths of cycb1 mutants were measured three days after transfer and the net root growth of three days is shown in the graphs.",
    "ncbi_link": "cycb1;2: 830502
cycb1;1: 829904
cycb1;3: 820325
cycb1;4: 817217"
  },
  {
    "caption": "K. The wildtype, cycb1;1, cycb1;2, cycb1;3, cycb1;4, cycb1;1/1;2, cycb1;1/1;3, cycb1;1/1;4, cycb1;2/1;4, cycb1;3/1;4 from left to right on plates containing 30 μM cisplatin 6 days after germination, i.e. 3 days after transfer from control plates.L. cycb1 double mutants germinated on control plates and were transferred to new control plates three days after germination. Root lengths were measured three days after transfer and the net root growth of three days is shown in the graphs.M. cycb1 mutants germinated on control plates and were transferred to plates supplemented with 15 μM cisplatin three days after germination. Root lengths of cycb1 mutants were measured three days after transfer and the net root growth of three days is shown in the graphs.N. cycb1 mutants germinated on control plates and were transferred to plates supplemented with 30 μM cisplatin three days after germination. Root lengths of cycb1 mutants were measured three days after transfer and the net root growth of three days is shown in the graphs.",
    "ncbi_link": "cycb1;2: 830502
cycb1;1: 829904
cycb1;3: 820325
cycb1;4: 817217"
  },
  {
    "caption": "A. Representative examples of comets of 21 days old wild-type plants, cdkb1;1 cdkb1;2 and cycb1;1 cycb1;3 double mutant seedlings in full spectrum view of the TriTek Comet Score software. Shown are comets of plants incubated with 50µM cisplatin for one hour and then transferred to medium without cisplatin for 30 min (recovery) and plants incubated without cisplatin for one hour (control), respectively.B. Box plot of percentage of tail DNA of wild-type cells, cdkb1;1 cdkb1;2 and cycb1;1 cycb1;3 under cisplatin treatment. Plots are based on analyses of 200 cells per sample from random microscopic fields of three independent biological replications. The percentage of DNA fragments in the comet tail was calculated by the TriTek Comet Score software. The box represents the interquartile range, the line across the box indicates the median values and whiskers represent 5-95 percentile values. Brackets connect plots of sample groups that are significantly different with a confidence level higher than 99.99% calculated with Student's t-test.",
    "ncbi_link": " cdkb1;1: 824585
cdkb1;1: 824585
cdkb1;2: 818444
cycb1;1: 829904
cycb1;3: 820325"
  },
  {
    "caption": "B. Wild-type plants show blue spots on the leaves after three days of incubation on 30 μM cisplatin. Arrows indicate representative blue sectors.C. cycb1;1 plants show blue spots on the leaves after three days of incubation on 30 μM cisplatin. Arrows indicate representative blue sectors.",
    "ncbi_link": "cycb1;1: 829904"
  },
  {
    "caption": "A. The wildtype and CDKA;1-DE mutants were grown on control plates for 10 days. Root lengths were measured 10 days after germination.B. The wildtype and CDKA;1-DE mutants were grown on plates containing 1 mM hydroxy urea for 10 days. The mutant wee1 was used as a positive control for hydroxy urea sensitivity. Root lengths were measured 10 days after germination.C. The wildtype and CDKA;1-DE mutants were grown on plates containing 0,6 μg/mL bleomycin for 10 days. The mutant ku70 was used as a positive control for bleomycin sensitivity. Root lengths were measured 10 days after germination.D. The wildtype, cdkb1;1, cdkb1;2 and the double mutant cdkb1;1 cdkb1;2 were grown on control plates for 10 days. Root lengths were measured 10 days after germination.E. The wildtype, cdkb1;1, cdkb1;2 and the double mutant cdkb1;1 cdkb1;2 were grown on plates containing 1 mM hydroxy urea for 10 days The mutant wee1 was used as a positive control for hydroxy urea sensitivity. Root lengths were measured 10 days after germination.F. The wildtype, cdkb1;1, cdkb1;2 and the double mutant cdkb1;1 cdkb1;2 were grown on plates containing 0,6 μg/mL bleomycin for 10 days. The mutant ku70 was used as a positive control for bleomycin sensitivity. Root lengths were measured 10 days after germination.",
    "ncbi_link": "CDKA;1: 824036
cdkb1;1: 824585
cdkb1;2: 818444
ku70: 838268
wee1: 839453"
  },
  {
    "caption": "G. The wildtype, CDKA;1-DE (grey bar) and the double mutant cdkb1;1cdkb1;2(purple bar) were grown on control plates and were transferred to plates containing 15 μM or 30 μM cisplatin three days after germination. Root lengths were measured three days after transfer and the net root growth of three days is shown in the graphs.H. Graphs represent the ratio of the mean growth rate on 15 μM cisplatin compared to control experiments on plates lacking cisplatin for the wildtype, CDKA;1-DE and cdkb1;1cdkb1;2.I. Graphs represent the ratio of the mean growth rate on 30 μM cisplatin compared to control experiments on plates lacking cisplatin for the wildtype, CDKA;1-DE and cdkb1;1cdkb1;2.",
    "ncbi_link": "CDKA;1: 824036
cdkb1;1: 824585
cdkb1;2: 818444"
  },
  {
    "caption": "J-N. Images show a wild-type plant, CDKA;1-DE and the double mutant cdkb1;1 cdkb1;2 (from left to right) on the indicated day after germination and the indicated drug treatment.",
    "ncbi_link": "CDKA;1: 824036
cdkb1;1: 824585
cdkb1;2: 818444"
  },
  {
    "caption": "A. WT and rad51 mutants were grown on control plates or transferred to plates supplemented with 15 μM or 30 μM cisplatin, respectively, three days after germination. Root lengths were measured three days after transfer and the net root growth of three days is shown in the graph. Asterisk indicates significant differences within a 5% confidence interval (Student's t-test).B. Image shows a wild-type plant (left) and rad51 mutant (right) grown on control plates. Images were taken 6 days after germination.C. Image shows a wild-type plant (left) and rad51 mutant (right) germinated on control plates and transferred to plates supplemented with 15 μM three days after germination. Images were taken 6 days after germination, i.e. 3 days after transfer to cisplatin.",
    "ncbi_link": "rad51: 832208"
  },
  {
    "caption": "A. Transgenic Arabidopsis plants harboring the CYCB1;1 promoter and a GFP fused to the N-terminal part of CYCB1;1 including the destruction box grown on control plates and imaged five days after germination.D. Transgenic Arabidopsis plants harboring the CYCB1;1 promoter and a GFP fused to the N-terminal part of CYCB1;1 including the destruction box germinated on control plates and were transferred four days after germination to plates supplemented with 50 μM cisplatin and were imaged 24h after drug application.",
    "ncbi_link": "CYCB1;1: 829904"
  },
  {
    "caption": "B. Transgenic Arabidopsis plants harboring the CYCB1;2 promoter and a GFP fused to the N-terminal part of CYCB1;2 including the destruction box grown on control plates and imaged five days after germination.E. Transgenic Arabidopsis plants harboring the CYCB1;2 promoter and a GFP fused to the N-terminal part of CYCB1;2 including the destruction box germinated on control plates and were transferred four days after germination to plates supplemented with 50 μM cisplatin and were imaged 24h after drug application.",
    "ncbi_link": "CYCB1;2: 830502"
  },
  {
    "caption": "C. Transgenic Arabidopsis plants harboring CDKB1;1 promoter fused to GUS grown on control plates, were stained and imaged five days after germination.F. Transgenic Arabidopsis plants harboring CDKB1;1 promoter fused to GUS germinated on control plates and were transferred four days after germination on plates supplemented with 50 μM cisplatin and were stained and imaged 24h after drug application.",
    "ncbi_link": "GUS: 
CDKB1;1: 824585"
  },
  {
    "caption": "G. Chromatin immunoprecipitation (ChIP) of wild-type plants and PROSOG1:SOG1-Myc lines and anti-MYC antibody. The promoter region of CYCB1;1 is enriched in SOG1-MYC after cisplatin treatment.H. Structure of genes tested by ChIP with an antibody anti-MYC in PROSOG1:SOG1-Myc and wild-type plants. Red arrowheads indicate the primer binding sites for PCR. A total of four regions were tested as indicated by arrowheads. Asterisks indicates significant differences within a 5% confidence interval (Student's t-test).",
    "ncbi_link": "CYCB1;1: 829904
SOG1: 839145"
  },
  {
    "caption": "A. The wildtype, ku70, the double mutants cycb1;1 ku70, cycb1;2 ku70 and cycb1;1cycb1;2 and the triple mutant cycb1;1cycb1;2ku70 were grown on control plates and root lengths were measured 10 days after germination.B. The wildtype, ku70, the double mutants cycb1;1 ku70, cycb1;2 ku70 and cycb1;1cycb1;2 and the triple mutant cycb1;1cycb1;2ku70 were grown on plates containing 0,6 μg/mL BLM. Root lengths were measured 10 days after germination.C. Graph represents the ratio of the mean growth rate on 0,6 µg/mL BLM compared to control experiments on plates lacking BLM for the wildtype, ku70, cycb1;1 ku70, cycb1;2 ku70 and cycb1;1cycb1;2 and the triple mutant cycb1;1cycb1;2ku70.",
    "ncbi_link": "cycb1;2: 830502
cycb1;1: 829904
ku70: 838268"
  },
  {
    "caption": "D. Image shows the wildtype, ku70, the double mutants cycb1;1 ku70, cycb1;2 ku70 and cycb1;1cycb1;2 and the triple mutant cycb1;1cycb1;2ku70 (from left to right) grown on control plates 10 days after germination.E. Images show the wildtype, ku70, the double mutants cycb1;1 ku70, cycb1;2 ku70 and cycb1;1cycb1;2 and the triple mutant cycb1;1cycb1;2ku70 (from left to right) on plates containing 0,6 μg/mL BLM.",
    "ncbi_link": "cycb1;2: 830502
cycb1;1: 829904
ku70: 838268"
  },
  {
    "caption": "(A) Mean clinical scores (±SEM) of C57BL/6→C57BL/6 controls treated with DTX and CD11c-DTR/GFP→C57BL/6 treated with DTX or PBS during the whole observation period starting from day -1. All animals received in vitro-generated 2d2.tdRFP Th17 intravenously on day 0. DC depletion in CD11c-DTR/GFP→C57BL/6 reduces the encephalitogenicity of adoptively transferred 2d2.tdRFP Th17. Mann-Whitney-U-test was performed on mean clinical scores (n=11PBS/13DTX); * p < 0.05, ** p < 0.01; see also Appendix Table S1. Pooled data from two independent experiments.",
    "ncbi_link": "DTR: 15200
CD11c: 16411"
  },
  {
    "caption": "(B) Mononuclear cells were isolated on day 30 of animals shown in (A) from the CNS of PBS- and DTX-treated CD11c-DTR/GFP→C57BL/6 that had been transferred with 2d2.tdRFP Th17. Flow cytometry was performed on surface stained cell samples. Cells were pre-gated on lymphocyte cells (FSC SSC gate) and PI-negative; pooled data of three animals; representative of two independent experiments.",
    "ncbi_link": "DTR: 15200
CD11c: 16411"
  },
  {
    "caption": "(C) Mononuclear cells were isolated from the CNS of PBS- and DTX-treated 2d2.tdRFPTh17-transferred CD11c-DTR/GFP→C57BL/6mice 2-3 d after onset of the disease. Upper panels: cells were stimulated with plate-bound anti-CD3/anti-CD28, stained for CD4 and cytokines IFN-y, IL-17 (pre-gated in addition to FSC/SSC on CD45+CD4+). Lower panels: expression of transcription factor FoxP3; pooled data from three animals, representative for two independent experiments.(D), (E) Quantification of cytokine expression data as shown in (C) for pooled data from 2 independent experiments; Mann-Whitney-U-Test * p < 0.05.",
    "ncbi_link": "DTR: 15200
CD11c: 16411"
  },
  {
    "caption": "(F) 2d2Th17 were transferred into lymphopenic Rag2-/-c-gamma-/-. Mononuclear cells were isolated from the spleen and brain at the peak of the disease and analyzed for IL-17 and GM-CSF production after stimulation with anti-CD3/anti-CD28.(G) GM-CSF production of IL-17 producers versus IL-17 non-producers of CNS-isolated 2d2Th17 cells (see also (F)). Each dot/square represents a single animal; Kruskal-Wallis-test; * p < 0.05, ** p < 0.01, **** p < 0.0001.",
    "ncbi_link": "c-gamma: 16186
Rag2: 19374"
  },
  {
    "caption": "TPLSM of EAE lesions in the brainstem of adoptive transfer EAE at the onset of the disease. EAE was induced by transfer of in vitro differentiated 2d2Th17 cells (tdRFP-red, IL-17-EGFP-green) into CD11c-DTR/GFPmice (CD11c-GFP - green); imaging area 300 × 300 µm.(A) Intravascular IL-17hi2d2Th17 cell (arrow, double positive -> green: IL-17EGFP and red: 2d2.tdRFP) rolling cell towards a CD11c-GFP+ cell (arrowhead). White dotted lines mark a venous vessel.(B) Time-lapse TPLSM (maximal intensity projections) of the boxed area in (A) shows that the perivascular elongated CD11c-GFP+ cell (asterisk) enters into contact with IL-17-expressing (GFP - green and 2d2.tdRFP - red double-positive; arrow and arrow head) Th17 cells (scale bar: 20 µm).(C) XYZ-resolved TPLSM depiction reveals that the elongated perivascular CD11c-GFP+ cell makes contact with the intravascular 2d2Th17 cells via a filopodium-like dendrite (xy-plane, 300 × 300 µm, z-depth 70 µm).",
    "ncbi_link": "CD11c: 16411"
  },
  {
    "caption": "(I) Quantification of the motility pattern of IL-17hi 2d2.tdRFP vs. all 2d2.tdRFP in CD11c-DTR/GFP brainstem lesions before and after (2-5 h) intraperitoneal DTX injection. Evaluation of mean track velocity of the single cell tracking (each dot represents a track); pooled data from at least two independent experiments (>3 imaging areas). For the statistical analysis, the Mann-Whitney-U-test was performed (*** p < 0.0001, n.s. = not significant).(K) Percentage of stopping cells (red bar; instantaneous velocity <2 µm/min) of the data set as shown in (I).",
    "ncbi_link": "CD11c: 16411"
  },
  {
    "caption": "(A) CD11c+ cells, CD4+ cells and CX3CR1+CD45intIAb+ (microglia) cells were isolated from peak EAE animals from the CNS. Samples from 6-11 animals were pooled in each experiment; at least two experiments were performed for each subset. Depicted are normalized mRNA expression (to expression in spleen CD11c+ cells) levels as determined by qRT-PCR analysis relative to the housekeeping genes Eukaryotic translation elongation factor 1 alpha 1 (Eef1a1) and Peptidylprolyl isomerase A (Ppia). CNS CD11c+ cells show gene expression of the inflammatory chemokines Ccl2, Ccl5, Cxcl9, Cxcl10 but not Il23 (mean ± SEM).(C) Quantitative expression of EAE-relevant factors Il23 and Csf2 were investigated in the CNS samples as described above",
    "ncbi_link": "Eef1a1: 
Ppia: 
Ccl2: 20296
Ccl5: 20304
Csf2: 12981
Cxcl10: 15945
Cxcl9: 17329
Il23: 83430"
  },
  {
    "caption": "(B) CD11c+ cells, CD4+ cells and CD11c-CD11b+IAb+ (monocytes/macrophages) were isolated from EAE affected mice as described in (A). Samples from 6-11 animals were pooled in each experiment; at least two experiments were performed for each subset. Depicted are normalized mRNA expression (to expression in spleenCD11c+ cells) levels as determined by qRT-PCR analysis relative to the housekeeping genes Eukaryotic translation elongation factor 1 alpha 1 (Eef1a1) and Peptidylprolyl isomerase A (Ppia). Relevantly regulated chemokines in other cell populations than CNS CD11c+ cells are shown (mean ± SEM).(D) Quantitative expression of EAE-relevant factors Il23 and Csf2 were investigated in the spleen samples.",
    "ncbi_link": "Eef1a1: 
Ppia: 
Csf2: 12981
Il23: 83430"
  },
  {
    "caption": "Figure 5Chemokine expression profiling of CD11c+ cells in the spleen and CNS reveal a key role of CNSCD11c+ cells for inflammatory chemokines.(A) CD11c+ cells, CD4+ cells and CX3CR1+CD45intIAb+ (microglia) cells were isolated from peak EAE animals from the CNS. Samples from 6-11 animals were pooled in each experiment; at least two experiments were performed for each subset. Depicted are normalized mRNA expression (to expression in spleenCD11c+ cells) levels as determined by qRT-PCR analysis relative to the housekeeping genes Eukaryotic translation elongation factor 1 alpha 1 (Eef1a1) and Peptidylprolyl isomerase A (Ppia). CNSCD11c+ cells show gene expression of the inflammatory chemokines Ccl2, Ccl5, Cxcl9, Cxcl10 but not Ccl20 (mean ± SEM).(B) CD11c+ cells, CD4+ cells and CD11c-CD11b+IAb+ (monocytes/macrophages) were isolated from EAE affected mice as described in (A). Relevantly regulated chemokines in other cell populations than CNSCD11c+ cells are shown (mean ± SEM).(C) Quantitative expression of EAE-relevant factors Il23 and Csf2 were investigated in the CNS samples as described above and (D) the spleen samples.Statistical significance was determined using Kruskal-Wallis test. P-values < 0.05 were regarded as statistically significant. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.",
    "ncbi_link": "Eef1a1: 
Ppia: 
Ccl2: 20296
Ccl20: 20297
Ccl5: 20304
Csf2: 12981
Cxcl10: 15945
Cxcl9: 17329
Il23: 83430"
  },
  {
    "caption": "B Confocal images of HeLa cells transiently expressing GFP-CBPs or GFP. The dotted lines show each cell shape. Scale bars, 10 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "C Confocal images of HeLa cells transiently expressing GFP-CbpCT4 and mCherry-LC3 (upper). The fluorescence intensities of GFP-CbpCT4 (green) and mCherry-LC3 (red) along the arrow are shown in the graph at the bottom.",
    "ncbi_link": "CbpC: 
GFP: 
mCherry: 
LC3: 64862"
  },
  {
    "caption": "D Lysates from 293T cells transiently expressing GFP-Cbps or GFP were subjected to SDS-PAGE and analyzed by immunoblotting using antibodies against LC3, GFP, or actin.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "E Lysates from 293T cells transiently expressing GFP-CbpCT4, GFP-LytR, or GFP in the presence or absence of chloroquine were subjected to SDS-PAGE and analyzed by immunoblotting using antibodies against LC3, GFP, or actin.",
    "ncbi_link": "CbpC: 
GFP: 
LytR: "
  },
  {
    "caption": "F MEFs were infected with S. pneumoniae R6 WT or ΔcbpF for the indicated periods, and the intracellular survival of bacteria expressed as the number of CFUs.",
    "ncbi_link": "cbpF: "
  },
  {
    "caption": "G p62-KO MEF cells infected with S. pneumoniae R6 ΔcbpF/pCbpFR6-FLAG for 2 h were fixed and stained with DAPI and an anti-FLAG antibody, and representative epifluorescence images are shown. Scale bars, 10 µm.",
    "ncbi_link": "cbpF: 
FLAG: 
p62: 18412"
  },
  {
    "caption": "F MEFs infected with R6 ΔcbpF expressing CbpFR6-FLAG for 2 h were subjected to IP and assayed using anti-HA agarose beads. The bound proteins were analyzed by immunoblotting using an anti-FLAG antibody.",
    "ncbi_link": "cbpF: "
  },
  {
    "caption": "A Lysates from MEFs stably expressing HA-Atg14 infected with S. pneumoniae TIGR4 WT or ΔcbpC for 1, 2, or 3 h in the presence or absence of cycloheximide were subjected to SDS-PAGE and analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "cbpC: "
  },
  {
    "caption": "B MEFs/HA-Atg14 cells were infected with S. pneumoniae TIGR4 WT or ΔcbpC for 1, 2, or 3 h in the presence or absence of Bafilomycin A1 (BafA1). The lysates were subjected to SDS-PAGE and analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "cbpC: "
  },
  {
    "caption": "(C A549 cells were infected with S. pneumoniae R6 WT or ΔcbpC for 2 h and fixed and stained with DAPI and an anti-Atg14 Representative epifluorescence images are shown. Scale bars, 10 µm. The percentages of perinuclear-localizing Atg14 containing cells were quantified.",
    "ncbi_link": "cbpC: "
  },
  {
    "caption": "A549 cells were infected with S. pneumoniae R6 WT or ΔcbpC for 2 h and fixed and stained with DAPI and -GM130 antibody. Representative epifluorescence images are shown. Scale bars, 10 µm. The percentages of intact Golgi apparatus-containing cells were quantified.",
    "ncbi_link": "cbpC: "
  },
  {
    "caption": "G S. pneumoniae (Sp) invasion-permissive A549 cells (marked with GFP) and Sp invasion-non-permissive (pIgR knocked down) A549 cells were co-cultured at a 1:3 ratio. Atg14-disappearance experiments were conducted, and representative epifluorescence images are shown. Scale bars, 10 µm. The lines show each cell shape and the arrows show invasion-permissive A549 cells marked with GFP. H The percentages of perinuclear-localizing Atg14 containing cells in (G) were quantified.",
    "ncbi_link": "pIgR: 5284"
  },
  {
    "caption": "I Lysates from 293T cells transiently expressing GFP-CbpC or GFP, and HA-Atg14 were subjected to SDS-PAGE and analyzed by immunoblotting using antibodies against HA or GFP.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "J Lysates from 293T cells transiently expressing GFP-CbpCT4 or GFP were immunoprecipitated using GST-GFP-Nanobody. Additionally, beads were mixed with lysates from 293T cells transiently expressing p62-3Myc and HA-Atg14, and bound proteins were analyzed by immunoblotting.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "K A549 cells treated with the indicated siRNAs were infected with S. pneumoniae R6 WT or ΔcbpF for the indicated durations. The cells were fixed and stained with DAPI and an anti-Atg14 antibody, and percentages of perinuclear-localizing Atg14 containing cells were quantified.",
    "ncbi_link": "cbpF: "
  },
  {
    "caption": "L Lysates from MEFs stably expressing GFP-CbpCT4 or GFP in the presence or absence of rapamycin or chloroquine were subjected to SDS-PAGE and immunoblotted using antibodies against LC3 or p62.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "M Quantification of NanoBRET signals in 293A cells transiently expressing HaloTag-Stx17 and Nanoluc-Atg14 in the presence or absence of GFP-CbpC or GFP.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "B GST-pulldown assays performed using GST-CbpFR6 or GST and lysates from 293T cells expressing GFP-Atg14 derivatives or GFP. The bound proteins were analyzed by immunoblotting using an anti-GFP antibody.",
    "ncbi_link": "GFP: 
Atg14: 22863"
  },
  {
    "caption": "D, E GST-pulldown assays using GST-CbpFR6 derivatives and lysates from 293T cells expressing GFP-Atg14 CCD or GFP. The bound proteins were analyzed by immunoblotting using an anti-GFP antibody. Each GST-CbpFR6 derivative-bound bead was confirmed by Coomassie brilliant blue (CBB) staining.",
    "ncbi_link": "GFP: 
Atg14: 22863"
  },
  {
    "caption": "H GST-pulldown assays performed using GST-CbpFR6 mutants or GST and lysates from 293T cells expressing GFP-Atg14 CCD or GFP. The bound proteins were analyzed by immunoblotting using an anti-GFP antibody. Each GST-CbpFR6 mutant-bound bead was confirmed by CBB staining.",
    "ncbi_link": "GFP: 
Atg14: 22863"
  },
  {
    "caption": "I Lysates of 293T cells transiently expressing GFP-CbpCT4 mutants or GFP were subjected to SDS-PAGE and analyzed by immunoblotting using antibodies against LC3, GFP, or actin.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "J Confocal microscopy images of HeLa cells transiently expressing the indicated GFP-CbpCT4 mutants. Scale bars, 10 µm.",
    "ncbi_link": "CbpC: 
GFP: "
  },
  {
    "caption": "B Lysates from 293T cells transiently expressing p62-3Myc and GFP-CbpCT4 variants were immunoprecipitated using a GST-GFP-Nanobody fusion protein. Bound proteins were analyzed by immunoblotting.",
    "ncbi_link": "CbpC: 
GFP: 
Myc: 
p62: 8878"
  },
  {
    "caption": "E Lysates from 293T cells transiently expressing p62-3Myc and GFP-CbpCT4 variants were immunoprecipitated using the GST-GFP-Nanobody protein. Bound proteins were analyzed by immunoblotting.",
    "ncbi_link": "CbpC: 
GFP: 
Myc: 
p62: 8878"
  },
  {
    "caption": "G Lysates of 293T cells transiently expressing GFP-CbpCT4 and p62-3Myc variants were immunoprecipitated with the GST-GFP-Nanobody protein. Bound proteins were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "CbpC: 
GFP: 
Myc: 
p62: 8878"
  },
  {
    "caption": "D GST-pulldown assays using the indicated GST-fusion proteins or GST and lysates from 293T cells expressing GFP-Atg14 CCD or GFP. Bound proteins were analyzed by immunoblotting using an anti-GFP antibody.",
    "ncbi_link": "GST: 
Atg14: 22863"
  },
  {
    "caption": "E Lysates from 293T cells expressing GFP-fusion proteins or GFP were subjected to SDS-PAGE and analyzed by immunoblotting using antibodies against LC3, GFP, or actin.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "H, I GST-pulldown assays using the indicated GST-fused proteins or GST and lysates from 293T expressing GFP-Atg14 CCD or GFP. Bound proteins were analyzed by immunoblotting using an anti-GFP antibody.",
    "ncbi_link": "GFP: 
Atg14: 22863"
  },
  {
    "caption": "C. Frontal cortices of A53T α-syn heterozygous transgenic mice and control mice at the age of 9 months (old) or 2 months (young) were lysed and Western blot was performed with the indicated antibodies (n=3). *** P < 0.001 compared to WT, unpaired t-test.",
    "ncbi_link": "α-syn: 6622"
  },
  {
    "caption": "FcγRIIB KD SH-SY5Y cells were treated with 1 μM α-syn fibrils for 30 min. The cells were lysed and Western blot was performed with the indicated antibodies. Images are representative of three independent experiments (n=3). *** P < 0.001, ** P < 0.01, * P < 0.05 compared to PBS, one-way ANOVA.",
    "ncbi_link": "FcγRIIB: 2213"
  },
  {
    "caption": "SHP-1 KD SH-SY5Y cells were treated with 1 μM α-syn fibrils for 30 min. The cells were lysed and Western blot was performed with the indicated antibodies. Images are representative of three independent experiments (n=3). *** P < 0.001, ** P < 0.01, * P < 0.05 compared to PBS, one-way ANOVA.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "SHP-2 KD SH-SY5Y cells were treated with 1 μM α-syn fibrils for 30 min. The cells were lysed and Western blot was performed with the indicated antibodies. Images are representative of three independent experiments (n=3). *** P < 0.001, ** P < 0.01, * P < 0.05 compared to PBS, one-way ANOVA.",
    "ncbi_link": "SHP-2: 27240"
  },
  {
    "caption": "SH-SY5Y cells were cocultured with differentiated A53T α-syn-EGFP OE SH-SY5Y cells in the presence of 5 μM saracatinib (sara) or 10 μM SKI-1 for 12 h. The cells in the lower chamber were fixed and immunostained with anti-EGFP antibody. The intensity was analyzed. Values were derived from four independent experiments (n=4). *** P < 0.001 against PBS, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622"
  },
  {
    "caption": "NT, c-src KD #1 and #2 SH-SY5Y cells were cocultured with differentiated A53T α-syn-EGFP OE SH-SY5Y cells for 12 h, and then fixed and immunostained with anti-EGFP antibody. Values were derived from four independent experiments (n=4). *** P < 0.001 compared to NT cells, one-way ANOVA",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 6714"
  },
  {
    "caption": ", D. primary cortical neurons were cocultured with differentiated A53T α-syn-EGFP OE SH-SY5Y cells in the presence of 5 μM saracatinib (sara) or 10 μM SKI-1 for 12 h. The cells in the lower chamber were fixed and immunostained with anti-EGFP antibody. The intensity was analyzed. Values were derived from four independent experiments (n=4). *** P < 0.001 against PBS, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622"
  },
  {
    "caption": ", E. primary cortical neurons downregulating c-src were cocultured with differentiated A53T α-syn-EGFP OE SH-SY5Y cells for 12 h, and then fixed and immunostained with anti-EGFP antibody. Values were derived from four independent experiments (n=4). *** P < 0.001 compared to NT cells one-way ANOVA unpaired t-test",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 83805"
  },
  {
    "caption": "SH-SY5Y cells were transfected with plasmids of WT c-src, Y529F c-src (kinase active), or K297M c-src (kinase dead) tagged with EGFP. After 1 day, the cells were cocultured with differentiated α-syn OE SH-SY5Y cells for 12 h and then fixed and immunostained with anti-α-syn antibody. The intensity was analyzed. Values were derived from three independent experiments (n=3). *** P < 0.001, * P < 0.05 compared to mock positive cells, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 20779"
  },
  {
    "caption": "G. FcγRIIB KD SH-SY5Y cells were transfected with plasmids of WT c-src, Y529F c-src (kinase active), or K297M c-src (kinase dead) tagged with EGFP. After 1 day, the cells were cocultured with differentiated α-syn OE SH-SY5Y cells for 12 h and then fixed and immunostained with anti-α-syn antibody. The intensity was analyzed. Values were derived from three independent experiments (n=3). *** P < 0.001, * P < 0.05 compared to mock positive cells, one-way ANOVA.",
    "ncbi_link": "EGFP: 
FcγRIIB: 2213
α-syn: 6622
c-src: 20779"
  },
  {
    "caption": "B. A53T α-syn-EGFP and A53T α-syn-mCherry OE SH-SY5Y cells were cocultured in the presence of 5 μM saracatinib (sara) or 10 μM SKI-1, respectively, with 50 μM RA for 5 days.",
    "ncbi_link": "EGFP: 
mCherry: 
α-syn: 6622"
  },
  {
    "caption": "C. NT or c-src KD #1 or #2 /A53T α-syn-EGFP and A53T α-syn-mCherry OE SH-SY5Y cells were cocultured with 50 μM RA for 5 days. The samples were observed under confocal microscopy, and the number of cells containing double fluorescence labeled puncta were analyzed. Values were derived from five independent experiments (n=5). *** P < 0.001 compared to PBS or NT cells, one-way ANOVA.",
    "ncbi_link": "EGFP: 
mCherry: 
α-syn: 6622
c-src: 6714"
  },
  {
    "caption": "A. Differentiated A53T α-syn-EGFP OE SH-SY5Y cells were incubated with 5 μM saracatinib (sara) or 10 μM SKI-1 for 12 h.",
    "ncbi_link": "EGFP: 
α-syn: 6622"
  },
  {
    "caption": "B. Differentiated NT, c-src KD #1 or c-src KD#2/A53T α-syn-EGFP OE SH-SY5Y cells were cultured 12 h. Levels of α-syn in culture media were then measured using ELISA. Values were derived from three independent experiments (n=3). *** P < 0.001, ** P < 0.01 compared to control, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 6714"
  },
  {
    "caption": "D. SH-SY5Y cells in the lower chamber were cocultured with differentiated NT, c-src KD #1 or c-src KD #2/ A53T α-syn-EGFP OE SH-SY5Y cells for 12 h. The cells in the lower chamber were immunostained with anti-EGFP antibody. The intensity was analyzed. Values were derived from five independent experiments (n=5). *** P < 0.001 compared to NT cells, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 6714"
  },
  {
    "caption": "E. Differentiated A53T α-syn-EGFP OE SH-SY5Y cells were incubated with 5 μM saracatinib (sara) or 10 μM SKI-1 in the presence of DMSO or 50 μM bafilomycin A1 (BafA) for 12 h.",
    "ncbi_link": "EGFP: 
α-syn: 6622"
  },
  {
    "caption": "Differentiated NT and c-src KD/A53T α-syn-EGFP OE SH-SY5Y cells were incubated with 50 μM BafA for 12 h. Western blot was performed. Data are representative of three independent experiments (n=3). *** P < 0.001, ** P < 0.01, * P < 0.05, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622
c-src: 6714"
  },
  {
    "caption": "G. NT and c-src KD primary neurons were incubated with 50 μM BafA for 12 h. Western blot was performed. Data are representative of three independent experiments (n=3). *** P < 0.001, ** P < 0.01, * P < 0.05, one-way ANOVA.",
    "ncbi_link": "c-src: 83805"
  },
  {
    "caption": "H. SH-SY5Y cells were cocultured with differentiated A53T α-syn-EGFP OE SH-SY5Y cells in the presence of DMSO or 50 μM BafA for 12 h. The cells were immunostained with anti-EGFP antibody. The intensity was analyzed. Values were derived from three independent experiments (n=3). ** P < 0.01, one-way ANOVA.",
    "ncbi_link": "EGFP: 
α-syn: 6622"
  },
  {
    "caption": "B. NT, c-src KD #1 or c-src KD #2 SH-SY5Y cells were incubated with 1 μM α-syn fibrils for 30 min and these cells were further incubated with 50 nM BODIPY FL C5-LacCer and 2.5 μg/ml rhodamine-conjugated transferrin for 20 min. The cells were fixed and observed under confocal microscopy. The intensity was analyzed. Values were derived from five independent experiments (n=5). *** P< 0.001 compared to control, one-way ANOVA.",
    "ncbi_link": "c-src: 6714"
  },
  {
    "caption": "G. Endogenous MITOL enhances the K48-polyubiquitin chains of Parkin. WT or MITOL KO HeLa cells stably expressing HA-Parkin were treated with CCCP (10 µM) for indicated time. MG132 (30 μM) was added 3 h after CCCP treatment. Lysates of cells were fractionated into cytosolic, mitochondrial and ER fractions, and then subjected to an IP-IB assay with the indicated antibodies. K48-polyubiquitin chains were immunoblotted with K48-specific ubiquitin antibody.",
    "ncbi_link": "MITOL: 54708"
  },
  {
    "caption": "E. MITOL regulates mitophagy. MITOL WT HeLa cells, MITOL KO HeLa cells and KO HeLa cells transfected with MITOL WT plasmids 0.5µg (+) and 5µg (++) stably expressing HA‐Parkin and mt‐Keima were treated with CCCP (10µM) for 8h. Then, mKeima was measured at 488 (pH 7) and 561 (pH 4) nm lasers using Flow Cytometer. Percentages of mitophagy were calculated from 30,000 cells in each independent experiment. Data represent the mean ± SD of three independent experiments. For statistical analysis, a one-way ANOVA with Tukey post-test was performed, **P < 0.01.",
    "ncbi_link": "MITOL: 54708"
  },
  {
    "caption": "C. Endogenous MITOL translocates to the ER in later phase of mitophagy. EGFP-MITOL knock in HeLa cells were transfected with HA-Parkin and treated with DMSO or CCCP (10 µM) as indicated times. Cells were fixed, permeabilized and subjected to immunofluorescence analysis with the indicated antibodies. Colocalization was quantified by Manders's coefficient. Means ± SEM of more than 10 cells obtained from three independent experiments. For statistical analysis, a one-way ANOVA with Tukey's multiple comparisons test were performed, ****P < 0.0001. Scale bar represents 1 μm.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "E. ER-localized MITOL is transported from the mitochondria, and is not newly synthesized protein. HeLa cells stably expressing HA-Parkin were co-transfected with vectors for MITOL-KikGR and FLAG-FKBP38. After ultraviolet light (365 nm) exposure to the whole plate, cells were incubated with or without CCCP (10 µM) for indicated time, and monitored for red and green KikGR fluorescence. Scale bar, 10 μm. Higher magnification images of the boxed regions are shown in the small panel. Right panel is schematic experimental model for KikGR in this study.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "C. Phosphorylated Parkin accumulates in the ER fraction in the absence of MITOL. WT or MITOL KO HeLa cells stably expressing HA-Parkin were treated with DMSO or CCCP (10 µM) for 48 h. Lysates of cells were fractionated into cytosolic, mitochondrial and ER fractions, and then subjected to an IB assay with the indicated antibodies. Phospho-Ser65-Parkin is detected by using specific antibody. Right panels are the quantification of IB about Phospho-Ser65-Parkin protein levels of the ER fraction. The data represent the mean ± SD for three independent experiments. For statistical analysis, a one-way ANOVA with Tukey post-test was performed, **P < 0.01.",
    "ncbi_link": "HA: 
MITOL: 54708"
  },
  {
    "caption": "D. Parkin is detected at the ER in the absence of MITOL. HeLa cells were transfected with vectors for KikGR-Parkin. After ultraviolet light (365 nm) exposure to the whole plate, cells were incubated with or without CCCP (10 µM) for indicated time, and monitored for red and green KikGR fluorescence. Scale bar, 10 μm. Higher magnification images of the boxed regions are shown in the small panel.",
    "ncbi_link": "KikGR: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "D. MITOL KO increases degradation of ER targeting FKBP38. HeLa cells stably expressing HA-Parkin were transfected with mitochondrial targeting FLAG-FKBP38 (FKBP38ActA) and ER targeting FLAG-FKBP38 (FKBP38IYFFT), and treated with DMSO or CCCP (10 µM) for 24 h. Lysates of cells were subjected to an IB assay with FLAG antibodies for organelle targeting FKBP38 or indicated antibodies. Another cell lysates were subsequently separated on a Phos-tag gel, followed by IB with anti-Parkin antibodies (Phos-tag).",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "E-G. MITOL partly prevents CCCP-induced cell death by reducing Parkin-mediated degradation of FKBP38. WT or MITOL KO HeLa cells stably expressing HA-Parkin and HeLa cells were transfected with the indicated vectors, and treated with DMSO or CCCP (10 µM) for 24 h. Cells were stained with propidium iodide (PI) for counting the percentage of dead cells using fluorescence microscopy. Data represent the mean ± SD of five independent experiments (>100 individual cells were counted). For statistical analysis, a one-way ANOVA with Tukey post-test was performed, **P < 0.01. KR, FKBP38 K271/273R.",
    "ncbi_link": "HA: 
FKBP38: 23770
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "A. Mislocalization of Bcl-2 is observed in MITOL KO cells in mitophagy. WT or MITOL KO HeLa cells stably expressing HA-Parkin were transfected with FLAG-Bcl2 and treated with DMSO or CCCP (10 µM) for the indicated times. Cells were immunostained with indicated antibody. Scale bar, 1 μm.",
    "ncbi_link": "HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "B. MITOL prevents caspase-dependent cell death in mitophagy. WT or MITOL KO HeLa cells stably expressing HA-Parkin and HeLa cells were treated with DMSO or CCCP (10 µM) with or without Z-VAD-FMK (10 μM) for 24 h. Cells were stained with propidium iodide (PI) for counting fluorescence microscopy of the percentage of dead cells. Data represent the mean ± SD of three independent experiments (>100 individual cells were counted). For statistical analysis, a one-way ANOVA with Tukey post-test was performed, **P < 0.01. C. Cell death in mitophagy caused by MITOL deficiency depends on calcium leak. WT and MITOL KO HeLa cells stably expressing HA-Parkin or HeLa cells were treated with DMSO or CCCP (10 µM) with or without BAPTA-AM (10 μM) for 24 h. Cells were stained with propidium iodide (PI) for counting fluorescence microscopy of the percentage of dead cells. Data represent the mean ± SD of three independent experiments (>100 individual cells were counted). For statistical analysis, a one-way ANOVA with Tukey post-test was performed, **P < 0.01. ",
    "ncbi_link": "caspase: 
HA: 
MITOL: 54708
Parkin: 5071"
  },
  {
    "caption": "(A, B) B-ALL progression measured as (A) absolute  number  or (B) percentage of OFP+ cells in  peripheral blood  of transplanted mice  (mean ± SD, each dot represents an individual mouse, CTRL = 6 mice, IFNγ   = 10  mice; **** p ≤ 0.001, Two-Way ANOVA; mice in blue and yellow (B) were also analyzed by single-cell RNA sequencing",
    "ncbi_link": "IFNγ: 15978"
  },
  {
    "caption": "(A) Engraftment of  CD45.2  donor cells and lineage composition following transplantation of wild-type (WT) or IFNγ receptor 1  knock out (KO) HSPCs transduced with either the control Tie2.NGFR (CTRL) or Tie2.IFNγ (IFNγ) LV  (mean ± SD, each dot represents an individual mouse, WT CTRL = 7 mice, WT IFNγ = 7  mice, KO CTRL = 7  mice, KO  IFNγ = 7 mice).",
    "ncbi_link": "IFNγ: 15978
IFNγ receptor 1: 15979
NGFR: 18053
Tie2: 21687"
  },
  {
    "caption": "(B, C) Violin plots show the distribution of IFNγ (B) and  MHC-II gene (C) signatures for each experimental condition, within each custom cell-type. Wilcox Rank Sum Test for IFNγ  signature, condition IFNγ d12 vs. CTR d12: B-ALL p= 2.68x10-19, B cells p=0.5, plasma cells p= 0.78; Wilcox Rank Sum Test for MHC-II  signature, condition  IFNγ d12 vs. CTRL d12: B-ALL p= 4.26x10-46, B cells p=1x10-9, plasma cells p= 0.32.",
    "ncbi_link": "IFNγ: 15978"
  },
  {
    "caption": "(F)  Expression of Mki67  transcripts in  B-ALL cells from CTRL d12 and IFNγ  d12 conditions, extracted from the scRNAseq   dataset (**** p ≤ 0.0001, Welch's test).",
    "ncbi_link": "IFNγ: 15978
Mki67: 17345"
  },
  {
    "caption": "(I) Loss of  IFNγ  response over  time in B-ALL  cells from the IFNγ  group, potentially facilitated by reduced expression of  Ifngr1, Ifngr2, Jak1, Stat1 and  Irf1 (data extracted from the scRNAseq  dataset statistical analysis by Two-Way ANOVA).",
    "ncbi_link": "IFNγ: 15978
Ifngr1: 15979
Ifngr2: 15980
Irf1: 16362
Jak1: 16451
Stat1: 20846"
  },
  {
    "caption": "Combination gene therapy  with IFNα, TNFα  and IFNγ, expressed from the Tie2 vector platform. CTRL (Tie2.NGFR), 2 independent experiments, n = 9  mice; IFNα, 1 experiment, n = 2 mice; IFNα/IFNγ, 1 experiment, n= 4 mice;  IFNα/TNFα, 1 experiment, n = 3 mice; IFNγ/TNFα, 2 independent experiments, n = 19  mice. (C) Percentage of MHC II+ macrophages  identified by  F4/80 expression in the spleen (mean ± SD, each dot represents an individual mouse; *p = 0.0484, **p = 0.0049, ordinary One-Way ANOVA). (D) Percentage of  CD8+ T lymphocytes within CD45  positive and OFP negative  splenic  cells (mean ± SD, each dot represents an individual mouse; *p = 0.0356, ordinary One-Way ANOVA). ( ",
    "ncbi_link": "IFNα: 111654
IFNγ: 15978
NGFR: 18053
Tie2: 21687
TNFα: 21926"
  },
  {
    "caption": "Combination of IFNγ gene therapy with immuno-oncology drugs. CTRL (Tie2.NGFR) + antibody isotype, n = 6 mice; CTRL +  αCTLA4 antibody, n= 5 mice; CTRL +  αLAG3  antibody, n = 5 mice; CTRL + 1-Methyltryptophan  (1-MT), n = 5  mice; IFNγ (Tie2.IFNγ) + antibody isotype, n = 7 mice; IFNγ  + αCTLA4 antibody, n = 7 mice; IFNγ + αLAG3 antibody, n = 7 mice; IFNγ +1-MT, n = 5 mice. (F) Percentage of MHC II+ macrophages identified by  F4/80 expression in the spleen (mean ± SD, each dot represents an individual mouse; **p ≤ 0.01, ***p ≤ 0.001, **** p ≤ 0.0001 as compared to CTRL isotype, ordinary One-Way ANOVA). (G) Percentage of CD8+ T lymphocytes within OFP  negative  BM cells (mean ± SD, each dot represents an individual mouse). S ",
    "ncbi_link": "IFNγ: 15978
NGFR: 18053
Tie2: 21687"
  },
  {
    "caption": "H, I Bar graphs showing relative Rankl and Wnt4 transcript levels normalized to 36B4 expression in C57Bl6-derived mammary organoids treated for 6 hours with R5020 (H) or LNG (I) and either 10 μM or 100 μM enzalutamide, n=3 independent experiments.",
    "ncbi_link": "36B4: 11837
Rankl: 21943
Wnt4: 22417"
  },
  {
    "caption": "E Representative micrographs showing co-IF with anti-KI67 (red), and anti-hECAD (green) of xenografted milk ducts after 21 days treatment with vehicle or LNG. Scale bar, 50 μm. F Violin plot showing the percentage of KI67 and hECAD double+ cells of total hECAD+ cells, dots represent individual sectors counted in 3 different glands, control (n=30) or LNG (n=28), median (red), statistical significance was assessed by non-parametric Mann-Whitney test. G Bar plot showing relative transcript levels of MKI67 in xenografted glands from control (n=6) and LNG-treated (n=3) mice, Student's t-test. ",
    "ncbi_link": "MKI67: 4288"
  },
  {
    "caption": "D Graph showing in vivo growth of HBECs from a 20-year-old patient transduced with either sh scramble or shAR and treated with LNG. Points show means of radiance in individual glands ± SEM; n= 8-10 per treatment. Wilcoxon matched-pairs test.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "E Representative micrographs showing co-IF with anti-GFP (red), and anti-AR (green) antibodies on histological sections from glands xenografted with HBECs transduced either with sh scramble or shAR-expressing lentivirus. Scale bar, 50 μm. F Violin plot showing the percentage of AR- and GFP-double+ cells of total GFP+ cells in sh scramble (n=6) and shAR (n=12) conditions, dots represent individual sectors counted, median (red). Statistical significance was assessed by fitting a generalized linear mixed model with gamma distributions using CTRL as reference. Red line shows median. ",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "The diffusion times of Scc1-GFP at S phase (B) were measured in strains yIO664 (wild-type) and yEB005 (WPL1∆), and in auxin-depleted yEB002 (PDS5-AID), yAM085 (SCC3-AID) and yAM946 (ECO1-AID) cells. Data are shown as mean ± s.e.m. from at least three independent experiments. *: p< 10-5, **: p< 10-13.",
    "ncbi_link": "WPL1: "
  },
  {
    "caption": "The diffusion times of Scc1-GFP at G2 phase (C) and M phase (D) were measured in strains yIO664 (wild-type) and yEB005 (WPL1∆), and in auxin-depleted yEB002 (PDS5-AID), yAM085 (SCC3-AID) and yAM946 (ECO1-AID) cells. Data are shown as mean ± s.e.m. from at least three independent experiments. *: p< 10-5, **: p< 10-13.",
    "ncbi_link": "WPL1: "
  },
  {
    "caption": "B. The molecular brightness of different GFP tagged constructs was obtained with GFP monomer and GFP-GFP dimer as the brightness standard. Cells of strain yIO664 (SCC1-GFP) were analyzed throughout the cell cycle by PCH. To examine the effects of Wpl1, Pds5, and Eco1 on cohesin dimerization, the PCH analysis was repeated in strain yEB005 cells (SCC1-GFP WPL1∆), strain yEB002 cells (SCC1-GFP PDS5-AID), and yAM946 (SCC1-GFP ECO1-AID) in which Pds5-AID/Eco1-AID was depleted with auxin.",
    "ncbi_link": "Wpl1: 
WPL1: "
  },
  {
    "caption": " A, B In vivo substrate phosphorylations are assessed by Western blotting of 5 WT (CDKL5 +/Y) and 5 CDKL5 KO (CDKL5 -/Y) mouse cortical lysates using phosphospecific antibodies. EB2 pS222 and MAP1S pS812 are dramatically reduced in KOs. Quantification of substrate phosphorylation is normalized for total protein level. Student's t-test: n = 5 animals per genotype",
    "ncbi_link": "CDKL5: 382253"
  },
  {
    "caption": " C, D Developmental expression of CDKL5 and levels of its substrate phosphorylations in P4 - P50 cortex. CDKL5-dependent substrate phosphorylation is quantified by subtracting KO from WT levels for each age. n = 3 animals per age per genotype ",
    "ncbi_link": "CDKL5: 382253"
  },
  {
    "caption": " G CDKL5 WT and CDKL5 KO neurons in culture are co-stained with neuronal dendrite marker MAP2, EB2 and EB2 pS222. EB2 pS222 is lost in CDKL5 KO dendrites. Scale bar is 20 μm ",
    "ncbi_link": "CDKL5: 382253"
  },
  {
    "caption": " B - D In CDKL5 KOs (CDKL5 -/Y), comet distance (B) and lifetime (C) is increased when compared to WT (CDKL5 +/Y). Comet velocity (D) is unchanged. Student's t-test: n = 16/615 and 15/381 neurons/comets in WT and KO, respectively ",
    "ncbi_link": "CDKL5: 382253"
  },
  {
    "caption": " E Representative kymographs of CDKL5 WT and KO neurons transfected with control shRNA and MAP1S shRNA ",
    "ncbi_link": "CDKL5: 382253
MAP1S: 270058"
  },
  {
    "caption": " F Comet lifetime is higher in control shRNA expressing KOs than WTs. MAP1S shRNA expression reduces comet lifetime in KO neurons. EB2 shRNA-mediated knockdown does not alter microtubule dynamics in WT or KO. Tukey's multiple comparison: n = 12-15 neurons, 388-741 comets per condition ",
    "ncbi_link": "MAP1S: 270058
EB2: 212307"
  },
  {
    "caption": " A, B Representative stills (A) and kymographs (B) of TrkB-RFP overexpressed in dendrites of WT and CDKL5 KO DIV14 cortical neurons. Scale bar is 5 μm. C, D No significant change is observed in the ratio of dynamic vs stationary vesicles (C) or anterograde vs retrograde runs (D). S = stationary, D = dynamic, A = anterograde, R = retrograde. Vesicles with a net distance > 5 μm were considered dynamic. E, F Both anterograde and retrograde runs show a trend towards reduced velocity in CDKL5 KO neurons (E). Anterograde run lengths are significantly reduced in KO compared to WT neurons (F) ",
    "ncbi_link": "CDKL5: 382253"
  },
  {
    "caption": " B COS-7 cells expressing HA-MAP1S LC, Flag-CDKL5 WT / kinase dead (KD) is shown with endogenous α-tubulin staining. MAP1S does not localize to microtubules when phosphorylated by CDKL5. Scale bar is 20 μm ",
    "ncbi_link": "CDKL5: 6792"
  },
  {
    "caption": "(B) Fractionation of HeLa cells overexpressing either HSP27 or the P182L mutant by a 10% to 80% sucrose gradient. Western blot against anti-V5 is shown.",
    "ncbi_link": "HSP27: 3315"
  },
  {
    "caption": "(C) Expression of V5-epitope-tagged HSP27 (WT or P182L mutant) in HSP27 knock-out HeLa cells and immunostaining of HSP27. The scale bars correspond to the non-expanded dimensions, derived by dividing by the sample expansion factor of 4.3. (D) The P182L mutation decreases the density of HSP27 spots upon detection of local fluorescence intensity maxima and quantification of the number of detected spots in expanded samples (n = 30). The error bar is the standard deviation for the different cytoplasmic regions. (E) Distribution of the intensity of individual spots (n = 3342) after Gaussian fitting of fluorescence intensity in the neighborhood of detected spots.",
    "ncbi_link": "V5: 
HSP27: 3315"
  },
  {
    "caption": "(F) Immunostaining of HSP27 (white) in motor neurons differentiated from CMT patient-derived iPSCs that harbor the heterozygous P182L mutation reveals large, cytoplasmic aggregates (center and right panels). The control motor neurons that contain WT HSP27 do not show evidence of any aggregates. The nucleus is stained with Hoechst (blue). Scale bar, 10 µm.",
    "ncbi_link": "HSP27: 3315"
  },
  {
    "caption": "(C-D) Co-immunoprecipitation from HeLa cells stably overexpressing V5-epitope-tagged HSP27 (WT or P182L mutant) using anti-V5 beads. Co-immunoprecipitation was quantified and presented as a percentage relative to the P182L variant (n=3). The mean ± one standard deviation (n=3) is shown. Right: the location of Pro182 (red) in the crystal structure of peptide-bound cHSP27 (PDB: 4mjh) and in silico creation of the P182L mutation (blue). The peptide is shown in white sticks. P182L specifically weakens binding of the HSP27 IxI/V motif.",
    "ncbi_link": "V5: 
HSP27: 3315"
  },
  {
    "caption": "(E) Co-immunoprecipitation from HeLa cells stably overexpressing V5-epitope-tagged HSP27 (WT or P182L mutant) and transiently transfected with BAG3-eGFP (WT or IPV-mutant) using anti-GFP beads. Western blots for anti-GFP (BAG3), V5 (HSPB1), and α-tubulin. NS indicates a non-specific band. Note that detection of BAG3 (anti-GFP) and HSP27 (anti-V5) occurs with different antibodies. The locations of the IPV-to-GPG mutations in BAG3 are depicted below.",
    "ncbi_link": "eGFP: 
V5: 
BAG3: 9531
HSP27: 3315"
  },
  {
    "caption": "(F) Co-immunoprecipitation from HeLa cells transiently transfected with V5-epitope-tagged HSP27 (P182L or S155Q/P182L mutant) using anti-V5 beads (n=2). Right: the location of Ser155 (red) in the crystal structure of peptide-bound cHSP27 (PDB: 4mjh) and in silico creation of the S155Q mutation (purple) showing a clash with the bound peptide. The peptide is shown in white sticks.S155Q disrupts binding of all IxI/V motifs.",
    "ncbi_link": "V5: 
HSP27: 3315"
  },
  {
    "caption": "Montages of representative DAPI-stained nuclei are shown for gene knockdowns that led to reduced nuclear size. Cell-to-cell variability in the amount of ELYS knockdown likely accounts for apparent nuclear size variability. Ten nuclei per column, organized by maximum nuclear size z-score. Scale bar, 25 µm. Median nuclear size z-scores are plotted for gene knockdowns that led to reduced nuclear size. Data are based on three different siRNA oligo sequences for each gene and two biological replicates. Error bars represent the SEM for biological replicates.",
    "ncbi_link": "ELYS: 25909"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with control or ELYS siRNA. (A) Representative images of cells stained for lamin B2 and B1 are shown. (B) Representative images of cells stained for lamin A/C and B1 are shown. (C) For each experiment, nuclear lamin B1, B2, and A/C staining intensities were quantified for 44-159 nuclei per condition (96 nuclei on average) and normalized to the negative control. Three biological replicates, data from one representative experiment shown. (D) Representative images of cells stained for FG-Nups (mAb414) and lamin B1 are shown. (E) Representative images of cells stained for Nup133 and lamin B1 are shown. (F) For each experiment, nuclear mAb414 and Nup133 staining intensities were quantified for 31-83 nuclei per condition (60 nuclei on average) and normalized to the negative control. To measure NPC densities, confocal NE surface images were acquired for mAb414 and Nup133 stained nuclei. NPC numbers were counted per unit area for 18-50 nuclei per condition (30 nuclei on average) and normalized to the negative control. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "ELYS: 25909"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with control or ELYS siRNA. Representative images of cells stained for Ran and lamin B1 are shown. (H) Representative images of cells stained for NTF2 and lamin A/C are shown. (I) Nuclear Ran and NTF2 staining intensities were quantified and normalized to the negative control. To measure the N/C staining intensity ratio of a given cell, the average fluorescence intensity of a nuclear region was divided by the average fluorescence intensity of a cytoplasmic region. For each experiment, 54-216 nuclei were quantified per condition (112 nuclei on average). Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "ELYS: 25909"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were co-transfected with control or ELYS siRNA and plasmids expressing eGFP alone or siRNA-resistant eGFP-ELYS. Cell lysates were analyzed by western blot and probed for ELYS and tubulin. ELYS band intensity was normalized to tubulin and then normalized to the eGFP/negative siRNA control. ELYS concentrations are indicated in the row labeled [ELYS] (average ± SD). Quantification was performed on two biological replicates. Cells were stained with an antibody against lamin B1. Representative images are shown. (B) For each experiment, nuclear cross-sectional areas were quantified for 68-298 nuclei per condition (162 nuclei on average) and averaged. Three biological replicates, data from one representative experiment shown. (C) For each experiment, nuclear lamin B2 staining intensities were quantified for 29-81 nuclei per condition (60 nuclei on average) and normalized to the eGFP/negative siRNA control. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "eGFP: 
ELYS: 226747
ELYS: 25909"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were co-transfected with control or ELYS siRNA and plasmids expressing mCherry alone or mCherry-importin α. Cells were stained with an antibody against lamin B2. Representative images are shown. Scale bar, 10 µm. (B) For each experiment, nuclear cross-sectional areas were quantified for 30-172 nuclei per condition (84 nuclei on average) and averaged. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "mCherry: 
ELYS: 25909
importin α: 3838"
  },
  {
    "caption": "For each experiment, nuclear lamin B2 staining intensities were quantified for 34-187 nuclei per condition (85 nuclei on average) and normalized to the mCherry/negative siRNA control. To measure bulk import capacity for importin α/β cargos, cells were co-transfected as in (A) along with a plasmid expressing GFP-3x SV40 NLS. For each experiment, nuclear GFP-NLS intensities were quantified for 22-188 nuclei per condition (73 nuclei on average) and normalized to the mCherry/negative siRNA control. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "GFP: 
mCherry: "
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with plasmids expressing mCherry alone or mCherry-RanQ69L and stained with an antibody against lamin B2. Representative images are shown.",
    "ncbi_link": "mCherry: 
Ran: 5901"
  },
  {
    "caption": "To measure bulk import capacity for importin α/β cargos, experiments were performed as in (A-B) except that cells were also transfected with a plasmid expressing GFP-3x SV40 NLS. For each experiment, nuclear GFP-NLS intensities were quantified for 11-75 nuclei per condition (35 nuclei on average) and normalized to the appropriate control. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Cell lysates from control and XPO1 siRNA transfected MCF-10AT1k.cl2 cells were analyzed by western blot and probed for XPO1 and tubulin. One representative western blot is shown. XPO1 band intensity was normalized to tubulin. Quantification from two biological replicates is shown.",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with control or XPO1 siRNA. Lamin B1 and lamin A/C nuclear staining intensities were quantified based on experiments using two different XPO1 siRNA sequences and two biological replicates. For each experiment, 108-865 nuclei were quantified per condition (416 nuclei on average). Average and SD values based on averages from these four experiments are plotted, normalized to the negative siRNA control.",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with control siRNA or with siRNA against XPO1. Cells were stained with DAPI and quantification of DNA staining intensity was used to estimate the fraction of cells in various stages of the cell cycle by high-throughput imaging as previously described [123] (see Methods). The stacked bars represent the means of the fractions for each cell cycle phase calculated over 3 biological replicates.",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "MCF-10AT1k.cl2 cells were transfected with control or XPO1 siRNA. For the bottom row of images, cells transfected with control siRNA were treated with 20 ng/ml leptomycin B for 24 hours. Cells were fixed and stained with 2 µg/ml FITC. Representative images are shown. Scale bar, 20 µm. For each experiment, nuclear cross-sectional areas and nuclear FITC staining intensities were quantified for 105-620 nuclei per condition (267 nuclei on average) and normalized to the negative control. Two biological replicates, data from one representative experiment shown.",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "A-E. Behavioural tests of APP/PS1mice. (B-D) Y-maze and passive avoidance tests on 7-month-old APP/PS1mice after Nec-1 administration for 12 weeks. Average alternation (%) for each test group (B) and total entry number into each arm (C) on Y-maze. (D) Average latency time in seconds for each test group on passive avoidance test.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "A-E. Behavioural tests of APP/PS1mice. (E) Survival of Wt and APP/PS1mice after injection of Nec-1 (6.25 mg/kg).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "4-month-old APP/PS1 (n = 13, male) and age-matched wild-type (Wt, n = 14, male) mice were intravenously injected with Nec-1 (6.25 mg/kg) or vehicle (2.5% DMSO in PBS) for 12 weeks. After the completion of behavioural tests, the brains of each group of mice were subjected to analysis.A. ThS-stained insoluble Aβplaques in whole brain and the hippocampal region of each group. Scale bars = 1 mM (upper), 200 μM (lower).B-G. Statistics of ThS-positive Aβplaques in the brains of APP/PS1mice. Total numbers and areas of ThS-positive Aβplaques in the whole brains (B and C), cortex (D and E) and hippocampus (F and G).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "A. Immunohistochemical analysis of cortical and hippocampal regions of the brains in wild-type (Wt) and APP/PS1mice after administration of Nec-1 (6.25 mg/kg) or vehicle (2.5% DMSO in PBS). Diffuse plaques in the brain sections were stained by anti-Aβ antibody (6E10 clone, green colour) and anti-GFAP antibody (red colour). Hoechst 33342 (blue colour) was applied for nuclear counterstaining. Scale bars = 200 μM.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "B-D. Dot blot analysis of total Aβ (anti-Aβ: 6E10 clone, also recognizes APP) and protein oligomer (anti-amyloidogenic protein oligomer A11) in the cortical (B) and hippocampal (C) region of indicated groups. (D) Quantification analysis of total Aβ and protein oligomer in the cortical and hippocampal region of indicated groups. Relative intensity of each band was determined by densitometry of dot blots (B and C) using ImageJ software and normalized to vehicle-administered APP/PS1mouse group.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "B-D. Dot blot analysis of total Aβ (anti-Aβ: 6E10 clone, also recognizes APP) and protein oligomer (anti-amyloidogenic protein oligomer A11) in the cortical (B) and hippocampal (C) region of indicated groups. (D) Quantification analysis of total Aβ and protein oligomer in the cortical and hippocampal region of indicated groups. Relative intensity of each band was determined by densitometry of dot blots (B and C) using ImageJ software and normalized to vehicle-administered APP/PS1mouse group.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "E. Sandwich ELISA of Aβ-soluble and -insoluble fractions from cortical and hippocampal lysates of APP/PS1mice.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "F. Western blot analyses of cortical and hippocampal lysates from APP/PS1mice for APP and sAPP expressions.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "A. Western blot analysis of phosphorylation levels of tau and expression levels of indicated proteins in the cortical and hippocampal regions of the brain in APP/PS1mice after administration of Nec-1 (6.25 mg/kg) or vehicle (2.5% DMSO in PBS). The membranes analysed in (A) are identical to those in Fig 5F.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "B. Immunohistochemical analysis of cortical and hippocampal regions of the brains in wild-type (Wt) and APP/PS1mice after administration of Nec-1 (6.25 mg/kg) or vehicle (2.5% DMSO in PBS) for phosphorylated tau expression levels. Anti-tau (phospho Ser199) antibody (red colour) was applied for staining tau phosphorylation on Serine-199 and Hoechst 33342 (blue colour) for nuclear counterstaining in the brain sections. Scale bars = 200 μM.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "C. Western blot analyses of phosphorylated RIPK3 expressions in cortex and hippocampus of APP/PS1mice injected with Nec-1 (upper). The membranes analysed in (C) are identical to those in Fig 1G and 5F.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(B) Effects of NAT feeding on expression of antioxidant enzymes, catalase, SOD1, and SOD2 (data are means ± SEM; n=10). *P<0.05 vs. zero time.",
    "ncbi_link": "catalase: 40048
SOD1: 39251
SOD2: 36878"
  },
  {
    "caption": "(E) Effects of NAT feeding on FoxO expression in the fat body of Drosophila larvae (data are means ± SEM; n=8). *P<0.05, **P<0.01 vs. zero time.",
    "ncbi_link": "FoxO: 41709"
  },
  {
    "caption": "(F) Effects of N-acetyltransferase (Dat) knockdown in gut enteroendocrine cells (TK-Gut-Gal4>UAS-dsDat) on survival of Drosophila larvae (data are means ± SEM; n=15). **P<0.01 vs. without NAT.",
    "ncbi_link": "Dat: 37867
N-acetyltransferase: 37867
Gal4: 855828"
  },
  {
    "caption": "(F) Effects of dsRNA targeting of FoxO on NAT-dependent expression of Keap1 (data are means ± SEM; n=12). *P<0.05, **P<0.01 vs. without NAT. Note that NAT feeding did not increase Keap1 expression in FoxO knockdown flies.",
    "ncbi_link": "FoxO: 41709
Keap1: 42062"
  },
  {
    "caption": "(A) Representative  images of WT, Mfn1 KO and Mfn2 KO MEFs transfected for 48 h with a plasmid encoding  mitochondria-targeted RFP (mt-RFP). Scale bar: 5 μm.",
    "ncbi_link": "Mfn1: 67414
Mfn2: 170731"
  },
  {
    "caption": "(A) Representative  images  of WT and Mfn2 KO MEFs co-transfected with plasmids encoding  mitochondria-targeted  RFP and  ER-targeted GFP. Scale bar: 5 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "I-K) Mitochondrial Ca2+ was determined in WT and Mfn2 KO MEFs loaded with Rhod2. The effect of (I) caffeine-induced (20 mM), (J)  IP3R activation with  ATP-induced (100 μM) and (K) histamine-induced (100 μM) ER Ca2+ release on mitochondrial Ca2+ was measured (n= 30 cells from 3 independent experiments). Data are presented as mean ± SEM.",
    "ncbi_link": "IP3R: 16439
Mfn2: 170731"
  },
  {
    "caption": "WT and  Mfn2  KO cells were transfected with plasmids encoding: GFP  and the indicated combination of non-targeting siRNA (siCT), siRNA targeting MCU (siMCU), ChiMERA or control (indicated as WT or Mfn2 alone) plasmids. (R) MMP was analyzed (n= 90 cells analyzed in 3 independent experiments).",
    "ncbi_link": "GFP: 
MCU: 215999
Mfn2: 170731"
  },
  {
    "caption": "WT and Mfn2 KO cells were transfected with plasmids encoding  GFP and the indicated combination of non-targeting siRNA (siCT), siRNA targeting MCU (siMCU), ChiMERA or control (indicated as WT or Mfn2 alone) plasmids. (S)  ATP levels of GFP+ cells was analyzed after 24 h treatment with  2DG (10 mM) (n= 3 independent experiments).",
    "ncbi_link": "GFP: 
MCU: 215999
Mfn2: 170731"
  },
  {
    "caption": "WT and  Mfn2 KO MEFs were co-transfected with plasmids encoding:  mt-RFP and  ER-Mfn2  or control (CT) plasmid. After 48 h, the cells were fixed. (C) Representative images. Scale bar= 5 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "WT and Mfn2 KO MEFs were co-transfected with plasmids encoding: J-N) GFP and  ER-Mfn2 or control (CT) plasmid. (J) MMP was determined. The values were normalized to surrounding untransfected cells. (n= 90 cells analyzed in 3 independent experiments). (K) After 24 h, the transfected cells were sorted and plated for another 24 h, after which cells were treated with 2-DG  (10 mM) for 6 h, and  ATP levels were measured (n= 3 independent experiments). (L) Oxygen consumption was measured and (M) RCR and (N) SRC was calculated (n= 4 independent experiments). Data are presented as mean ± SEM. Data information: *p<0.05, one-way ANOVA followed by Tukey's post hoc test. Note that experiments were performed at the same time, so the values of WT and Mfn2 KO transfected with control plasmid are the same but the figures have been split in two for the sake of linearity.",
    "ncbi_link": "Mfn2: 170731
Mfn2: 9927"
  },
  {
    "caption": "WT and  Mfn1/2 double KO were transfected with: A)  mt-RFP, ER-GFP and plasmids expressing the indicated proteins. Mitochondria-ER colocalization was analyzed using Mander's coefficient (n= 15 cells analyzed in 3 independent experiments). Data are presented as mean ± SEM. B)  GFP and ERMITO-RLuc and indicated expression vectors. After 24 h, the transfected cells were sorted and plated for another 24 h, after which RLuc was analyzed (n= 3 independent experiments). Data are presented as mean ± SEM. C) Data information: The red dashed line indicates the WT cells results. *p<0.05 versus Mfn1/2 DKO cells, one-way ANOVA followed by Tukey's post hoc test. Note that experiments were performed at the same time, so the values of WT and Mfn2 KO transfected with control plasmid are the same but the figures have been split in two for the sake of linearity.",
    "ncbi_link": "GFP: 
RFP: 
RLuc: 
Mfn1: 67414
Mfn2: 170731"
  },
  {
    "caption": "WT and Mfn1/2 double KO were transfected with: C) GFP  and the indicated plasmids. After 48 h,  mitochondrial Ca2+ was determined (n= 30 cells from 3 independent experiments). Data are presented as mean ± SEM. Data information: The red dashed line indicates the WT cells results. *p<0.05 versus Mfn1/2 DKO cells, one-way ANOVA followed by Tukey's post hoc test. Note that experiments were performed at the same time, so the values of WT and Mfn2 KO transfected with control plasmid are the same but the figures have been split in two for the sake of linearity.",
    "ncbi_link": "GFP: 
Mfn1: 67414
Mfn2: 170731"
  },
  {
    "caption": "WT and Mfn1/2 double KO were transfected with: D) LAR-GECO1 and the indicated plasmids. After 48 h  ER Ca2+ was released with caffeine (20 mM) as indicated (n= 25-27 cells from 3 independent experiments). Data are presented as mean ± SEM. Data information: The red dashed line indicates the WT cells results. *p<0.05 versus Mfn1/2 DKO cells, one-way ANOVA followed by Tukey's post hoc test. Note that experiments were performed at the same time, so the values of WT and Mfn2 KO transfected with control plasmid are the same but the figures have been split in two for the sake of linearity.",
    "ncbi_link": "Mfn1: 67414
Mfn2: 170731"
  },
  {
    "caption": "WT and Mfn1/2 double KO were transfected with: E) GFP and the indicated plasmid. After 48 h, the effect of caffeine-induced (20 mM) ER Ca2+ release on mitochondrial Ca2+ was measured (n= 25 cells from 3 independent experiments). Data are presented as mean ± SEM.",
    "ncbi_link": "GFP: 
Mfn1: 67414"
  },
  {
    "caption": "B) Representative  Western blots of the indicated proteins during the  neuronal maturation in vitro (n= 3 independent experiments). C) Representative Western blots of the indicated proteins of WT and  Mfn2 KO neurons at DIV7 (n= 3 independent experiments). D ",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "D) Primary neurons of tamoxifen-inducible Mfn2 KO  mice  were transfected at DIV3 with  ER-GFP,  mt-RFP  plus the indicated plasmids. Tamoxifen-treated (for 72 h) and vehicle-treated neurons (WT; red dashed line) were fixed and mitochondria-ER co-localization was analyzed using Mander's coefficient (n= 15 neurons analyzed in 3 independent experiments). Data are presented as mean ± SEM. Data information: *p<0.05 versus WT; #p<0.05 versus Mfn2 KO neurons, one-way ANOVA followed by Tukey's post-hoc test. Scale bar: 500 μm.",
    "ncbi_link": "GFP: 
RFP: 
Mfn2: 170731"
  },
  {
    "caption": "(F) neurite length  measurement and representative tracings (G) of primary cortical neurons of WT and Mfn2  KO  mice co-transfected at DIV4 with  GFP and the indicated plasmids. After 72 h, the  neurons were fixed,  immunofluorescence with anti-GFP antibodies was performed and  neurite length was measured (n= 30 neurons from 3 independent experiments). Data are presented as mean ± SEM. Data information: *p<0.05 versus WT; #p<0.05 versus Mfn2 KO neurons, one-way ANOVA followed by Tukey's post-hoc test. Scale bar: 500 μm. E ",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(E) Vacuoles were isolated from BJ3505 strains expressing the indicated tagged versions of Vam3 and Nyv1 and Pho8-EGFP or Pho8-mCherry. 10 µg of vacuoles were incubated in standard fusion reactions in the presence or absence of ATP and analyzed by confocal microscopy. Arrows indicate examples of fusion products. Scale bar: 5 µm. (F) Fusion activity: vacuole fusion was assayed by measuring the percentage of co-localization of the two Pho8-EGFP and Pho8-mCherry signals. Means s.d. are shown for at least 100 stained vacuoles from 3 experiments.",
    "ncbi_link": "Nyv1: 850782
Vam3: 854273"
  },
  {
    "caption": "(A) Vacuoles were isolated from BJ3505 cells expressing the indicated versions of Vam3 and/or Nyv1. 10 µg of the organelles were analyzed by SDS-PAGE and Western blotting using antibodies to Vti1, Vam3 and Nyv1.",
    "ncbi_link": "Nyv1: 850782
Vam3: 854273"
  },
  {
    "caption": "(B) and (C) SNARE activation on isolated vacuoles. Vacuoles were isolated from a strain co-expressing NYV1-S9-EGFP and VAM3-S9-mCitrine and from an isogenic wild-type. 150 µg of the organelles were incubated in fusion reactions in the presence or absence of an ATP-regenerating system and recombinant, purified Sec18/NSF (rSec18, 50 µg/ml). After 10 min of incubation at 27°C, the vacuoles were solubilized and immunoprecipitated with antibodies to Nyv1. Co-immunoprecipitated proteins analyzed by SDS-PAGE and Western blotting. The histograms provide quantifications of the band intensities as the means and s.d. from three independent experiments.",
    "ncbi_link": "NYV1: 850782
VAM3: 854273"
  },
  {
    "caption": "(C) Vacuoles were isolated from BJ3505 and DKY6281 cells with SNAREs tagged or deleted as indicated. Note that presence of Nyv1 on only one fusion partner still permits efficient fusion [65] but ensures that trans-SNARE complexes can only form in one orientation, between the Q-SNARE in DKY6281 and the R-SNARE in BJ3505. The vacuoles were used in standard fusion reactions and content mixing was measured via the alkaline phosphatase assay. In parallel, identical samples were incubated either incubated on ice, which prevents fusion, or in the presence of 0.5% Triton X-100, which allows fusion-independent access of the maturase Pep4 to pro-ALP and controls for the levels of these two reporter enzymes in the samples.",
    "ncbi_link": "Nyv1: 850782"
  },
  {
    "caption": "Vam3 and Nyv1 were tagged with mCitrine and EGFP as shown Fig. 3A but the spacer was extended (S34) by an additional 25-amino acid sequence (SGGGGSGGGGSGGGGSGGGGAAAGG) to the previous short spacer. (B) Vacuole morphology was assessed as in Fig. 3C. Scale bar: 5 µm. (C) The cells were grouped into three categories according to the number of vacuoles visible per 100 cells. Values represent the means and s. d. from three independent experiments.",
    "ncbi_link": "Nyv1: 850782
Vam3: 854273"
  },
  {
    "caption": "Vam3 and Nyv1 were tagged with mCitrine and EGFP as shown Fig. 3A but the spacer was extended (S34) by an additional 25-amino acid sequence (SGGGGSGGGGSGGGGSGGGGAAAGG) to the previous short spacer. (D) Fusion activity: vacuoles were isolated from BJ3505 strains expressing the indicated versions of Vam3 and Nyv1 and Pho8-mCFP or Pho8-mCherry. 10 µg of vacuoles were incubated in standard fusion reactions in the presence or absence of ATP and analyzed by confocal microscopy. Arrows indicate examples of fusion products. Means s.d. are shown for at least 100 stained vacuoles from 3 experiments. Scale bar: 5 µm. (E) Vacuole fusion was assayed by measuring the percentage of co-localisation of the two Pho8-mCFP and Pho8-mCherry signals.",
    "ncbi_link": "Nyv1: 850782
Vam3: 854273"
  },
  {
    "caption": "(E) Fusion activity. Vacuoles were isolated from BJ cells carrying Nyv1-S9-EGFP and DKY cells deleted for Nyv1 and carrying Vam3-S9-mCitrine or from wild-type cells and incubated in standard fusion reactions in the presence or absence of chlorpromazine (CPZ, 150 µM) and anti-Vam3 (3 µg). Content mixing was assayed via alkaline phosphatase activity. Means and s.d. are shown for three independent experiments.",
    "ncbi_link": "Nyv1: 850782
Vam3: 854273"
  },
  {
    "caption": " (E) Overexpression of hTLR4, hTLR4/hMD-2, hTLR4 (P714H) /MD-2 in HEK293T cells, and co-stimulation by GM3 22:0 with LPS (5 ng/mL). TLR4 activation was monitored by NF-κB luciferase reporter assay (termed "Relative Luc Activity" on Y-axis). ",
    "ncbi_link": "Luc: 
hMD-2: 23643
MD-2: 23643
NF-κB: 4790
hTLR4: 7099
TLR4: 7099"
  },
  {
    "caption": " (F, Co-stimulation of hTLR4/hMD-2 by GM3 species plus LPS (5 ng/mL) ",
    "ncbi_link": "hMD-2: 23643
hTLR4: 7099"
  },
  {
    "caption": " G) Co-stimulation of hTLR4/hMD-2 by GM3 species plus LPS (5 ng/mL) and further addition of soluble human CD14 (1 µg/mL) ",
    "ncbi_link": "hMD-2: 23643
hTLR4: 7099"
  },
  {
    "caption": " (H) Stimulation of Mal-overexpressing HEK293T cells by GM3 species. ",
    "ncbi_link": "Mal: 4118"
  },
  {
    "caption": " (I) Co-stimulation of hTLR4/hMD-2 by LPS (5 ng/mL) plus various mixtures of GM3 species. ",
    "ncbi_link": "hMD-2: 23643
hTLR4: 7099"
  },
  {
    "caption": " (d) Co-stimulation of mTLR4/mMD-2-expressing HEK293T cells by GM3 species plus LPS (2.5 ng/mL), and further addition of soluble mouse CD14-Fc fusion protein (1 µg/mL). ",
    "ncbi_link": "mMD-2: 17087
mTLR4: 21898"
  },
  {
    "caption": " (A) GM3 molecular species of 6-wk-old control C57/BL6 mice and ob/ob mice were analyzed respectively by LC-MS/MS (n=3). ",
    "ncbi_link": "ob: 16847"
  },
  {
    "caption": " (C, D) Alanine scanning for basic residues involved in signal transduction via VLCFA-GM3 (n=5) (C), and combinations of effective mutations (n=6) (D). Signal transduction was monitored by NF-κB reporter assay. ",
    "ncbi_link": "NF-κB: 4790"
  },
  {
    "caption": " (E-G) Comparative inhibitory effects of GM3 16:0 on mTLR4/mMD-2 (E), mTLR4/hMD-2 (domain-swapped complex) (F), and hTLR4/hMD-2 (G) (n=3). ",
    "ncbi_link": "hMD-2: 23643
mMD-2: 17087
hTLR4: 7099
mTLR4: 21898"
  },
  {
    "caption": " (H) Cross-linked SDS-PAGE analysis of recombinant mTLR4 (extracellular domain)/mMD-2 complexed with GM3 18:0, GM3 species enhancing mTLR4 activation. ",
    "ncbi_link": "mTLR4: 21898"
  },
  {
    "caption": "(C) The Chr.10:A and X:A ratios (top), and XIST expression (bottom) in human female germ cells in vivo and in cultured rOvaries analyzed by SC3-seq.",
    "ncbi_link": "XIST: 7503"
  },
  {
    "caption": "GFP trap IP of WT, Q78L and T33N RAB21 variants in HeLa cells followed by GFP immunoblot and endogenous (B) VPS26 immunoblot Lysates correspond to 5% of input, n≥ 3 independent experiments.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "GFP trap IP of WT, Q78L and T33N RAB21 variants in HeLa cells followed by GFP immunoblot and (C) FAM21, Strumpellin and VPS35 immunoblots. Lysates correspond to 5% of input, n≥ 3 independent experiments.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(A) Low RAB21 expression levels in two independent RAB21 KO cell populations. Immunoblot analysis of endogenous RAB21, RAB5, RAB7 and GAPDH.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(B) Endo-lysosomal compartments are unaffected by the loss of RAB21. Immunofluorescences of APPL1, TfR, RAB7 and LAMP1 in parental HeLa cells and in the two RAB21 knockout cell populations. Scale bars :10µm, n=3 independent experiments.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "The stability of the retromer cargo sorting complex is affected in RAB21 KO cells. Immunoblot analysis of VPS35, VPS26, VPS29, GAPDH and RAB21 in parental and the two RAB21 KO cell populations. Ratio of VPS35, VPS26 and VPS29 integrated densities to GAPDH for four independent experiments; SEM. * represents p <0.05 Statistical tests used: One sample t-tests All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(B) WASH complex proteins are not affected by RAB21 deletion. Immunoblot of Strumpellin, WASH, FAM21, CAPZα, GAPDH and RAB21. Ratio of WASH, FAM21, Strumpellin and CAPZα integrated densities to GAPDH for four independent experiments; SEM. Data information Statistical tests used: One sample t-tests All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "RAB21 knockout decreases VPS35 localization at endosomes. (C) Immunofluorescence of endogenous VPS35 and EEA1 in RAB21-depleted cells. Boxed region is magnified and single channel images are depicted. (D) Per cell Pearson Correlation between VPS35 and EEA1; SEM, n=3 independent experiments. Data information scale bars represent 10µm or 2.5µm in enlarged views. Statistical tests used: (D) - Unpaired t-tests All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "RAB21 knockout decreases VPS35 localization at endosomes. (E) Average number of VPS35 puncta per cell; SEM, n=3 independent experiments. Data information Statistical tests used: Mann-Whitney tests. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(F-H) RAB21 loss impairs endosomal recruitment of the WASH complex. (F) Immunofluorescence of endogenous WASH and EEA1 in RAB21-depleted cells. Boxed region is magnified and single channel images are depicted. (G) Per cell Pearson Correlation between VPS35 and EEA1 and (H) FAM21 and EEA1; SEM, n=2 independent experiments. Data information: scale bars represent 10µm or 2.5µm in enlarged views. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(I-J) RAB21 knockout reduces endosomal F-actin levels. (I) Immunofluorescence of endogenous F-actin using Alexa-488 conjugated phalloidin and EEA1 in RAB21-depleted cells. Boxed region is magnified and single channel images are depicted. (J) Per cell Pearson Correlation between internal F-actin and EEA1; SEM, n=3 independent experiments. Data information scale bars represent 10µm or 2.5µm in enlarged views. Statistical tests used: Mann-Whitney tests. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats.",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(A-C) RAB21 is not required for CI-MPR or GLUT1 trafficking. (A) Immunofluorescence of endogenous CI-MPR and TGN46 or GLUT1 with LAMP1 in RAB21-knockout cells. Boxed region is magnified. (B) Per cell Pearson Correlation between CI-MPR and TGN46 or (C) GLUT1 and LAMP1; SEM, n=3 independent experiments. Data information: In (A), scale bars represent 20µm or 5µm in enlarged views for CI-MPR, while they represent 10µm in enlarged views for GLUT1. Statistical tests used: (B) - Unpaired t-tests (C Mann-Whitney tests. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "MCT1 trafficking requires RAB21. (D) Immunofluorescence of endogenous MCT1 in wild type or RAB21-depleted cells. (E) Per cell integrated MCT1 intensity (in Relative Fluorescence Unit); SEM, n=2 independent experiments. Data information: scale bars represent 20µm or 5µm in enlarged views. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(G-H) RAB21 is required for appropriate SLC3A2, Basigin and CD44 trafficking. (G) Antibody-uptake assays in parental or knockout RAB21 cells. Cells were stained with an Alexa488 conjugated anti-mouse antibody. Arrowheads point to endosomal tubules. Note that non-internalized antibodies were removed by an acid wash, which was not fully efficient for CD147 and CD44, explaining plasma membrane labeling. (H) Percentage of cells with tubules in parental or RAB21 knockout cells; SEM, n=3 independent experiments. Data information scale bars represent 20µm or 5µm in enlarged views. Statistical tests used Mann-Whitney tests. All error bars are SEM. Number of cells presented on each graph represents the total number of cells analyzed for all repeats",
    "ncbi_link": "RAB21: 23011"
  },
  {
    "caption": "(A) Validation of WASH and retromer knockouts and SLC3A2 protein levels. Immunoblots of parental or FAM21, VARP and VPS29 knockout cell populations.",
    "ncbi_link": "FAM21: 
VARP: 84079
VPS29: 51699"
  },
  {
    "caption": "(B) Antibody-uptake assays in parental or knockout FAM21, VARP and VPS29 cells. Cells were stained with an Alexa488 conjugated anti-mouse antibody. Arrowheads point to endosomal tubules. Data information: (B) scale bars represent 20µm",
    "ncbi_link": "FAM21: 
VARP: 84079
VPS29: 51699"
  },
  {
    "caption": "Retromer is required for endosomal localization of RAB21. Immunofluorescence of transiently expressed GFP:RAB21 with endogenous (E) EEA1 in parental or VARP- and VPS29-deleted cells. Boxed region is magnified underneath. Data information scale bars represent 10µm or 2.5µm in enlarged views.",
    "ncbi_link": "VARP: 84079
VPS29: 51699"
  },
  {
    "caption": "Retromer is required for endosomal localization of RAB21. Immunofluorescence of transiently expressed GFP:RAB21 with endogenous (F) VPS26 in parental or VARP- and VPS29-deleted cells. Boxed region is magnified underneath. Data information: scale bars represent 10µm or 2.5µm in enlarged views.",
    "ncbi_link": "VARP: 84079
VPS29: 51699"
  },
  {
    "caption": "(E) Lk distributions of the control plasmid (YEp24) relaxed by lysates of ∆top1 top2-4 yeast cells that expressed TOP2 or Top2-∆83. Plots compare the relative intensity of individual Lk topoisomers.",
    "ncbi_link": "top1: 854156
top2: 855636"
  },
  {
    "caption": "(A) Top, DNA content (n/2n) of exponentially growing (OD600 = 0.6-0.8) smc2-8 yeast cells. First blot: 2D gel electrophoresis of the distribution of Lk topoisomers (Lk) of the YEp13 DNA in cells quenched at 26oC and after shifting the culture to 35oC for 60 min. Second blot: 2D gel electrophoresis of the same samples upon nicking the YEp13 DNA in order to reveal the occurrence of knots (kn). Graph: Pkn of YEp13 before and after the inactivation of condensin.",
    "ncbi_link": "smc2: 850589"
  },
  {
    "caption": "Top, DNA content (n/2n) of exponentially growing yeast cells. First blot: 2D gel electrophoresis of the distribution of Lk topoisomers (Lk) of the YEp13 DNA in cells quenched at 26oC and after shifting the culture to 35oC for 60 min. Second blot: 2D gel electrophoresis of the same samples upon nicking the YEp13 DNA in order to reveal the occurrence of knots (kn). (B) Experiments conducted as in (A) but in scc1-73 yeast cells. Graph: Pkn of YEp13 before and after the inactivation of cohesin.",
    "ncbi_link": "scc1: 851561"
  },
  {
    "caption": "Top, DNA content (n/2n) of exponentially growing yeast cells. First blot: 2D gel electrophoresis of the distribution of Lk topoisomers (Lk) of the YEp13 DNA in cells quenched at 26oC and after shifting the culture to 35oC for 60 min. Second blot: 2D gel electrophoresis of the same samples upon nicking the YEp13 DNA in order to reveal the occurrence of knots (kn). (C) Experiments conducted as in (A) but in smc6-9 yeast cells. Graph: Pkn of YEp13 before and after the inactivation of the Smc5/6 complex.",
    "ncbi_link": "smc6: 851099"
  },
  {
    "caption": "(A-E) DNA topology of the indicated minichromosomes of increasing DNA length (kb) before (26oC) and after inactivation of condensin (35oC) in smc2-8 cells. In each case, the first 2D gel resolves the Lk topoisomers (Lk), the second 2D gel uncovers the knotted forms (Kn). Gel signals are denoted as in Fig 2. Bottom graphs compare the Pkn before and after the inactivation of condensin (mean ± SD from three independent experiments). P-values (Student's t test): ns, p > 0.05; **p < 0.01; ***p < 0.001. ",
    "ncbi_link": "smc2: 850589"
  },
  {
    "caption": "(A-D) DNA topology of the indicated minichromosomes of increasing DNA length (kb) before (26oC) and after inactivation of cohesin (35oC) in scc1-73 cells. In each case, the first 2D gel resolves the Lk topoisomers (Lk), the second 2D gel uncovers the knotted forms (Kn). Gel signals are denoted as in Fig 2. Bottom graphs compare the Pkn before and after the inactivation of cohesin (mean ± SD from three independent experiments). P-values (Student's t test): ns, p > 0.05.",
    "ncbi_link": "scc1: 851561"
  },
  {
    "caption": "(A-D) DNA topology of the indicated minichromosomes of increasing DNA length (kb) before (26oC) and after inactivation of Smc5/6 complex (35oC) in smc6-9 cells. In each case, the first 2D gel resolves the Lk topoisomers (Lk), the second 2D gel uncovers the knotted forms (Kn). Gel signals are denoted as in Fig 2. Bottom graphs compare the Pkn before and after the inactivation of Smc5/6 complex (mean ± SD from two independent experiments).",
    "ncbi_link": "smc6: 851099"
  },
  {
    "caption": "(D) smFISH images showing LAT  RNA in  Ntrk1-positive neurons. SCG-derived cultures were infected with  HSV-1 in the presence of ACV and allowed to establish latency over 7 days before being processed for smFISH  using probes for HSV-1 LAT (green) and  neuronal  marker Ntrk1  (TrkA) (red) or fibroblast  marker Col3a1  (red). Signal intensities for the LAT  probe were quantified in neurons and fibroblasts and plotted by ImageJ. The percentage of LAT-positive cells were quantified and displayed as bar graphs with mean ± SEM. Left: 3 biological replicates, signal intensities of 50 cells were quantified for each replicate. Middle: 3 biological replicates, signal intensities of 30 cells were quantified for each replicate. Right: the blue and red dots represent the number of biological replicates done for quantification of each cell type. Scale bar, 10 μm. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).",
    "ncbi_link": "Col3a1: 84032
LAT: 24271498
Ntrk1: 59109
TrkA: 59109"
  },
  {
    "caption": "(A) smFISH images showing selected viral mRNAs in reactivating  neurons probed for  ICP27 (immediate-early), UL30 (early),  UL36 (true-late) or cellular markers, Ntrk (neurons), or  Col3a1 (fibroblasts). Nuclear  DNA was visualized using DAPI  (blue). To induce reactivation, latently-infected SCG-derived cultures were simultaneously treated with LY294002 (20 μM) and WAY-150138 (20 μg/mL) and cultured for 48 hrs prior to processing for smFISH. Scale bar, 10 μm.",
    "ncbi_link": "Col3a1: 84032
Ntrk: 59109
UL30: 2703462
UL36: 2703357
ICP27: 24271474"
  },
  {
    "caption": "(B) The percentage of cells positive for a viral mRNA or for GFP fluorescence was quantified at different time points and displayed as bar graphs with mean ± SEM. Latently-infected cultures were untreated (latent) or treated with  LY294002 and WAY-150138  for 18, 48, or 72 hrs. Each dot corresponds to the value from each biological replicate. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(C-D) Reactivating neurons probed simultaneously for two separate viral productive cycle mRNAs. Signal overlap is evident as white or yellow nuclear foci in the merge. Bar, 10 μm. In (D), the percentage of positive nuclei  with overlapping UL30 and UL36 smFISH signals were quantified as the mean ± SEM (n=3 biological replicates). Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test.",
    "ncbi_link": "UL30: 2703462
UL36: 2703357"
  },
  {
    "caption": "(B) Differential gene expression analysis of cellular transcripts showed a significant upregulation of at least 19 viral transcript units (TU) and a subset of cellular genes in neurons undergoing reactivation Three host transcripts were also downregulated. Gadd45b is highlighted with a green asterisk. Vertical hashed blue lines indicate Log2 fold changes >1.5 and < -1.5, while the horizontal hashed blue line indicates an adjusted p-value of 0.01. Significantly regulated genes are named and shown as magenta circles.",
    "ncbi_link": "Gadd45b: 299626"
  },
  {
    "caption": "(A)  smFISH images showing nuclear Gadd45b mRNA in latent (UL36-negative) neurons and nuclear/cytoplasmic Gadd45b  mRNA in viral  UL36-positive neurons. Latently-infected SCG neurons treated with  LY294002 and WAY-150138 for 48 hrs were processed using smFISH to detect Gadd45b (green) and viral UL36 (red) mRNA levels and colocalization. Nuclei  were stained with DAPI (blue). Scale bar, 10 μm. (B) smFISH images processed as in (A) showing  nuclear Gadd45b mRNA in uninfected neurons  at 48 hrs post treatment with LY294002. Scale bar, 10 μm.",
    "ncbi_link": "Gadd45b: 299626
UL36: 2703357"
  },
  {
    "caption": "(E) The percentage of HSV-1  latently-infected neurons or reactivating neurons  at 48 hrs post treatment with LY294002 and WAY-150138  were scored for either predominantly nuclear or nuclear/cytoplasmic Gadd45b mRNA  localization and displayed as mean ± SEM. Each purple dot represents a biological replicate experiment. (F) Quantification of nuclear or nuclear/cytoplasmic Gadd45b mRNA in uninfected neurons at 48 hrs post treatment with either LY294002 or in DMSO. Each light blue dot represents a biological replicate experiment. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ****, p<0.0001).",
    "ncbi_link": "Gadd45b: 299626"
  },
  {
    "caption": "(H) Combined  smFISH and  immunofluorescence  (IF) images showing high GFP-expressing neurons (GFP-positive) or low  GFP-expressing (GFP absent) neurons simultaneously probed for   Gadd45b  mRNA. Reactivation was induced by treatment with  LY294002 and WAY-150138 for 60 hrs and processed for simultaneous smFISH and IF staining. Right panel shows quantification (as in G) of the smFISH signal intensity of Gadd45b mRNA and IF  signal intensity of GFP protein at 48 hrs post treatment with LY294002 and WAY-150138 (n=3 biological replicates). The signal intensity was quantified, plotted, and analysed by ImageJ. Bar, 10 μm. Data information: : R and R square values were calculated using Correlation analysis by Prism 8.",
    "ncbi_link": "Gadd45b: 299626"
  },
  {
    "caption": "(A) Viral DNA polymerase inhibitor  phosphonoacetic acid (PAA, 300 μg/ml) treatment suppressed Gadd45b mRNA expression. Latently-infected SCG neurons were treated with LY294002 for 18 hrs to induce reactivation then treated with or without PAA  until the termination time-points  indicated. RNA was then collected and levels of Gadd45b mRNA quantified by RT-qPCR (n=3 biological replicates, the bars and error bars are mean ± SD). Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test.",
    "ncbi_link": "Gadd45b: 299626"
  },
  {
    "caption": "(G) Latent SCG neurons  treated with  LY294002 and WAY-150138 for 72 hrs, the Gadd45b nuclear  puncta-presenting neurons  were ICP4  negative (none observed in over 60   Gadd45b nuclear  puncta-positive  neurons), but a small population (~5%) in Gadd45b nuclear-enriched neurons were  ICP4 positive. Scale bar, 20 μm.",
    "ncbi_link": "ICP4: 2703392"
  },
  {
    "caption": "(A) Depletion of  Gadd45b  expression using lentiviral-transduced shRNAs in latently-infected  SCG neurons  case cause HSV-1  reactivation. HSV1-GFP-Us11 latently-infected cultures were infected with lentiviruses expressing either two different shRNAs against Gadd45b mRNA or a non-silencing shRNA (NS). Reactivation was quantified by scoring the percentage of wells expressing GFP  after 5 days. Knockdown efficiencies for individual shRNAs in latently-infected SCG neurons were confirmed by RT-qPCR using RNA collected in parallel. Reactivation rates were quantified from 30 wells for each condition, 3 biological replicates. RT-qPCR were quantified from 3 biological replicates. The bars and error bars are mean ± SD. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).",
    "ncbi_link": "Gadd45b: 299626"
  },
  {
    "caption": "(B) smFISH shows that depletion of Gadd45b leads to increased UL36 expression. smFISH was performed 3 days post-lentiviral transduction. smFISH  signals were quantified and plotted using ImageJ and Prism. Left: 3 biological replicates, 30 cells were quantified for each replicate. The horizonal lines are mean. Right: 3 biological replicates. The horizonal lines and error bars are mean ± SD.",
    "ncbi_link": "Gadd45b: 299626
UL36: 2703357"
  },
  {
    "caption": "(C) Ectopic expression of Gadd45b-Myc-Flag  inhibits viral mRNA  expression. Lentivirus-delivered ectopic expression of Gadd45b-Myc-Flag in SCG neurons  was confirmed by immunoblotting. Latently-infected SCG neurons  were transduced with Gadd45b-Myc-Flag for 3 days and then treated with LY294002 and WAY-150138 to induce reactivation. RNA was collected at the indicated time-points (LY treatment for 18 or 72 hours) and levels of viral  UL36 mRNA quantified by RT-qPCR. 3 biological replicates. The bars and error bars are mean ± SD. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).",
    "ncbi_link": "Flag: 
Myc: 
Gadd45b: 299626
UL36: 2703357"
  },
  {
    "caption": "(D) Ectopic expression of Gadd45b-Myc-Flag antagonizes LY294002-induced HSV-1 reactivation. Latently-infected SCG neurons were either transduced with vector control (Ctrl) or Gadd45b-Myc-Flag  from  lentivirus for 3 days prior to addition of LY294002. Reactivation was quantified by scoring the percentage of wells expressing  GFP fluorescence at the indicated days. The percentage of wells expressing GFP-positive was scored as the mean ± SEM (n=3 biological replicates). Reactivation rates were quantified from 30 wells for each condition, 3 biological replicates.",
    "ncbi_link": "Flag: 
Myc: 
Gadd45b: 299626"
  },
  {
    "caption": "(F) Ectopic expression of Gadd45b-Myc-Flag  suppressed viral  ICP4 mRNA expression. Latently-infected SCG neurons were transduced with Gadd45b for 3 days and then treated with LY294002 and WAY-150138 for 72 hrs. Viral ICP4 mRNA was quantified by qRT-PCR. 3 biological replicates. The bars and error bars are mean ± SD. Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).",
    "ncbi_link": "Flag: 
Myc: 
Gadd45b: 299626
ICP4: 2703392"
  },
  {
    "caption": "(G)  Immunoblots for viral  ICP4  protein in latent SCG neurons treated with LY294002  and WAY-150138 in the presence or absence of  Gadd45b-Myc-Flag was quantified by ImageJ (n=3 biological replicates). Data information: P values equal to or less than 0.05 were considered significant, asterisks denote statistical significance (*, p<0.05; ***, p<0.001; ****, p<0.0001). P values are calculated using two-tailed unpaired Student's t test. P values > 0.05 were not significant (ns).",
    "ncbi_link": "Flag: 
Myc: 
Gadd45b: 299626"
  },
  {
    "caption": "c, Knockdown of NetB  in the  eye disc  of GMR-RasV12 flies  enhances survival. d, NetB  heterozygous mutant flies survive  better over  Rasv12-induced oncogenic stress. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by Dunnett's multiple comparisons test (c) and two-tailed unpaired t-test d, *P < 0.05, **P <0.01, ****P <0.0001.",
    "ncbi_link": "NetB: 32400
Ras: 41140"
  },
  {
    "caption": "f, qRT-PCR  with mRNA from the  eye disc confirms higher expression of NetB  in GMR-RasV12 flies  Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by two-tailed unpaired t-test *P < 0.05, **P <0.01, ****P <0.0001.",
    "ncbi_link": "NetB: 32400
Ras: 41140"
  },
  {
    "caption": "g-h, Oncogenic Ras  expression in the eye disc  induces NetB  protein, which was detected by GFP  signal using CPTI-000748, a protein trap of NetB. Single confocal  z-section images are shown. i, Quantification of GFP  signals in g and h. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by two-tailed unpaired t-test *P < 0.05, **P <0.01, ****P <0.0001. Scale bar, 50 μm.",
    "ncbi_link": "Ras: 41140"
  },
  {
    "caption": "a-b, The amount of NetB  protein increases in the fat body GMR-RasV12 (a) compared to control flies  (b).  CPTI-000748, a protein trap of NetB, labels endogenous NetB. Data information: Scale bar, 20 μm (a-b",
    "ncbi_link": "Ras: 41140"
  },
  {
    "caption": "e-h, Ectopic expression of GFP-tagged NetB  in the  eye disc induces high levels GFP-NetB  protein in the fat body. Single confocal z-section are shown images (e and g). Data information: Scale bar, 20 μm f-h 50 μm",
    "ncbi_link": "GFP: 
NetB: 32400"
  },
  {
    "caption": "j-k, Ectopic expression of GFP-tagged NetB  in the eye disc leads to detection of GFP  signals in the hemolymph. Data information: Scale bar, 20 μm j-k)",
    "ncbi_link": "GFP: 
NetB: 32400"
  },
  {
    "caption": "a, Knockdown of InR  (InR) or expressing a dominant-negative form of InR  (InR-DN) in the  fat body using CG-Gal4  increases survival  over oncogenic Ras  expression in the imaginal disc. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by Dunnett's multiple comparisons test (a NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "Gal4: 855828
InR: 42549
Ras: 41140"
  },
  {
    "caption": "c, qRT-PCR  demonstrates that TMLHE  expression in the fat body  is reduced by Ras  expression in the eye disc and reversed by insulin  inhibition in the fat body. d, qRT-PCR demonstrates that NetB  knockdown in the eye disc increases TMLHE  expression in the fat body. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by Tukey's multiple comparison test (c and d) NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "TMLHE: 42421
insulin: 42549
NetB: 32400
Ras: 41140"
  },
  {
    "caption": "e, Knockdown of unc-5, but not other NetB  receptors (Fra  or Dscam1), in the  fat body increases TMLHE expression. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by one-way ANOVA followed by Dunnett's multiple comparisons test e). NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "TMLHE: 42421
Dscam1: 35652
Fra: 36377
unc-5: 36703"
  },
  {
    "caption": "b, Local expression of oncogenic Ras  in the eye disc  decreases the amount of carnitine  in the fat body. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by two-tailed unpaired t-test NS, not significant, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "Ras: 41140"
  },
  {
    "caption": "c, TMLHE  knockdown in the  fat body  aggravates organismal survival  over the oncogenic stress. d, In the absence of GMR-RasV12, inhibition of TMLHE  in the fat body is not sufficient to induce organismal death. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by two-tailed unpaired t-test NS, not significant, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "TMLHE: 42421
Ras: 41140"
  },
  {
    "caption": "g, Feeding of  acetyl-CoA precursor (acetate) makes GMR-RasV12 flies survive  even with TMLHE  knockdown in the fat body. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and the statistical significance was determined by two-tailed unpaired t-test NS, not significant, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "TMLHE: 42421
Ras: 41140"
  },
  {
    "caption": "e, qRT-PCR with mRNA from the adult gut  confirms higher expression of NetB  in esg ts>RasV12 flies  after oncogenic Ras  induction for 10 days. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and n represents the number of flies  that were analyzed. The statistical significance was determined by two-tailed unpaired t-test NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "esg: 34903
NetB: 32400
Ras: 41140"
  },
  {
    "caption": "f-g, Oncogenic Ras  expression in the adult gut  induces NetB  protein, which was detected by GFP  signal using CPTI-000748, a protein trap of NetB. Ras  was induced for 10 days. Single confocal  z-section images are shown. h, Quantification of GFP  signals in f and g. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and n represents the number of flies  that were analyzed. The statistical significance was determined by two-tailed unpaired t-test NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001. Scale bar, 50 μm.",
    "ncbi_link": "Ras: 41140"
  },
  {
    "caption": "i, Knockdown of NetB  in the adult gut  of esg ts>RasV12 flies  enhances survival. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and n represents the number of flies  that were analyzed. The experiments were repeated independently at least twice with similar results The statistical significance was determined by log-rank (Mantel-Cox) test NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "esg: 34903
NetB: 32400
Ras: 41140"
  },
  {
    "caption": "l, Knockdown of TMLHE  in the fat body  of adult flies  shortened lifespan of esgts>RasV12 flies  but not of control flies. Data information: Data points indicate biological replicates. Data are mean ± s.e.m. and n represents the number of flies  that were analyzed. The experiments were repeated independently at least twice with similar results The statistical significance was determined by log-rank (Mantel-Cox) test l). NS, not significant, *P < 0.05, **P <0.01, ***P <0.001, ****P <0.0001.",
    "ncbi_link": "TMLHE: 42421
esg: 34903
Ras: 41140"
  },
  {
    "caption": "A. Relative levels of OMA1 mRNA in colorectal cancer tissues (n=105) compared with adjacent normal tissues (n=43) from colorectal cancer patients were shown (using the GEO dataset GSE21510). The data are presented as mean ± SEM, and statistical significance was determined by a Mann-Whitney test. ***p < 0.001.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "B. Kaplan-Meier curves were constructed to analyze and compare between patients with high and low levels of OMA1 in colorectal cancer samples from the GEO dataset GSE17537. \"Low\" indicates patients with OMA1 mRNA levels less than the median. \"High\" indicates patients with OMA1 mRNA levels greater than the median. Statistical analysis was performed using log-rank tests, n = 55, p=0.0180.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "D. Control and OMA1 KO HCT116 cells were cultured in hypoxia (1% O2) for 0 (normoxia), 24, or 48 hours. Cell lysates were then assessed by Western blotting with antibodies against OPA1, OMA1, or β-Actin. β-Actin was used as a loading control. Representative immunoblots were from n = 3 independent experiments.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "E. OPA1-null mouse embryonic fibroblasts (MEFs) expressing control (empty vector) or OPA1 isoform 1 were cultured in normoxia or hypoxia (1% O2) for 24 hours. Cell lysates were analyzed by Western blotting with anti-OPA1 or anti-Tubulin antibody. Representative immunoblots were from n = 3 independent experiments.",
    "ncbi_link": "OPA1: 74143"
  },
  {
    "caption": "F. WT, OMA1 KO and OMA1 KO HCT116 cells expressing WT-OMA1(OMA1-Flag) or proteolytic inactive OMA1(E324Q-Flag) were cultured in hypoxia (1% O2) for 0, 24, or 48 hours, and the cell lysates were assessed by western blot with antibodies against OMA1, and GAPDH. β-Actin was used as a loading control (representative data from three independent experiments). The asterisk indicates a nonspecific band. G. The relative protein levels were evaluated by densitometry analysis using ImageJ software and were quantified for the ratio of OMA1-Flag/β-Actin or E324Q-Flag/β-Actin in hypoxia for 0, 24 or 48 hours (n = 3 independent experiments). The data are presented as mean ± SD. ",
    "ncbi_link": "Flag: 
OMA1: 115209"
  },
  {
    "caption": "B. Body weight changes of WT (n=11) and OMA1-/- (n=12) mice during AOM/DSS treatment. Data are presented as mean ± SEM. Statistical significance was assessed by a two-way ANOVA, **p < 0.01.",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "C. Typical intestine images on day 105 after mice were euthanized. D. Colorectal lengths (C) of WT (n=11 biological replicates) and OMA1-/- (n=12 biological replicates) mice were measured. Data with error bars are presented as mean ± SEM. Statistical significance was assessed by unpaired student's t-test, *p < 0.05. ",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "E. Representative images of colorectal tumors from WT (left) and OMA1-/- (right) mice. F. The number of tumors in WT (n=11) and OMA1-/- (n=12) mice was measured. Each dot represents the tumor number of one individual mouse. Data with error bars are presented as mean ± SEM. Statistical significance was assessed by unpaired student's t-test, ***p < 0.001. ",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "G, H. The number of tumors of different sizes (diameter) in each mouse (G) and the distribution of different tumor sizes (H) were shown (WT n=11 biological replicates, and OMA1-/- n=12 biological replicates). Results are shown as mean ± SEM. p-values were calculated by unpaired student's t-test, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "I. Histological analysis of colorectal tumors of WT and OMA1-/- mice was shown by hematoxylin and eosin (H&E) staining.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "J. Relative mRNA expression levels of pro-inflammatory genes (TNFα, IL-6, COX-2, CCL2) in colorectal homogenates of WT and OMA1_KO mice treated with AOM/DSS (n =4-5 per genotype). The data represent the mean ± SEM., n = 3 independent experiments, and statistical significance was determined by a two-tailed student's t-test. *p < 0.05, **p < 0.01.",
    "ncbi_link": "CCL2: 20296
COX-2: 17709
IL-6: 16193
OMA1: 67013
TNFα: 21926"
  },
  {
    "caption": "K. The colorectal tissues of WT and OMA1-/- mice were stained with Ki67.",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "A, B. Control or OMA1 KO HCT116 cells expressing control (empty vector) or OMA1-Flag were maintained in normoxia or hypoxia (1% O2) for 24 hours. The glucose uptake (A) and lactate production (B) were measured by using microplate reader, and the values were normalized to the protein concentration. Error bars indicate the mean ± SD of three independent experiments, statistical significance was assessed by a two-way ANOVA, *P < 0.05. Cells were lysed and assessed by western blot with antibodies against OMA1 and GAPDH (A). The asterisk indicates a nonspecific band.",
    "ncbi_link": "Flag: 
OMA1: 115209"
  },
  {
    "caption": "C. Control and OMA1 KO HCT116 cells were treated with DMSO or 1mM DMOG in fresh medium for 12 h. Subsequent injections of glucose, oligomycin (Oligo), and 2-deoxy-glucose (2-DG) were performed as indicated. The extracellular acidification rates (ECAR) were measured with a Seahorse Extracellular Flux Analyzer XF96. The data are presented as mean ± SD (n = 3 independent experiments).",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "E, F. Lactate production (E) and ATP production (F) were measured in control or OPA1 KO HCT116 cells upon DMSO or 2-DG treatment. Error bars are presented as mean ± SD by a two-way ANOVA (n = 3 independent experiments). N.S., not significant, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "OPA1: 74143"
  },
  {
    "caption": "G, H. Control or OPA1 KO HCT116 cells were maintained in normoxia or hypoxia (1% O2) for 24 hours. The glucose uptake (G) and lactate production (H) were measured, and the values were normalized to the protein concentration. Statistical significance was assessed by a two-way ANOVA; error bars are presented as mean ± SD of three independent experiments; N.S., not significant, *p < 0.05, **p < 0.01.",
    "ncbi_link": "OPA1: 74143"
  },
  {
    "caption": "A. Control and OMA1 KO HCT116 cells were cultured in normoxia or in hypoxia (1% O2) for 24 or 48 hours. The whole cell lysates were analyzed by Western blotting with antibodies against HIF-1α, HK2, LDHA, PKM2, GPI, OMA1, or β-Actin. The relative protein levels were further evaluated by densitometry analysis using ImageJ software and were presented as bar graphs in the right panels. Error bars are presented as mean ± SD by a two-way ANOVA (n = 3 independent experiments). *p<0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "B. Control or OMA1 KO Hela cells were untreated (-) or CoCl2-treated (+) for 24 hours with 10 mM MG132 or vehicle added for the last 4 hours. Cell lysates were assessed by Western blotting with antibodies against HIF-1α or β-Actin. Relative protein levels were further evaluated by densitometry analysis. Error bars indicate the mean ± SD by a two-way ANOVA (n = 3 independent experiments). *p<0.05, **p < 0.01.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "C. Dihydroethidium (DHE) staining of optimum cutting temperature (OCT) covered tissues from the colons of WT and OMA1-/- mice; DAPI was used as counterstain. DHE was shown in red color, while DAPI in blue color (representative data from three independent experiments). D. Quantification of DHE staining. Error bars are presented as mean ± SD (n=3 biological replicates), statistical significance was assessed by a two-way ANOVA, **p < 0.01, ***P< 0.001. ",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "E. Control or OMA1 KO HCT116 cells cultured in normoxia or hypoxia (1% O2) for 12 hours were stained with mitoSOX, and then analyzed by confocal microscopy (representative data from three independent experiments). F. The fluorescence intensity of mitoSOX was further analyzed by ImageJ software. Bars indicate the mean ± SD of three independent experiments by a two-way ANOVA, ***p < 0.001. ",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "G-I. Control or OMA1_KO HCT116 cells were cultured in normoxia or hypoxia for 12 hours, and were treated with DMSO, NAC (10 mM) or Rotenone (1 μM) for 12 hours at the same time. The whole cell lysates were analyzed by Western blotting with antibodies against HIF-1α, and Tubulin (G). The glucose uptake (H) and lactate production (I) were measured using microplate reader, and the values were normalized to the protein concentration. Error bars indicate the mean ± SD (n = 3 independent experiments), statistical significance was assessed by two-way ANOVA. N.S., not significant, *P < 0.05, ***P< 0.001.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "A. 293T cells were transiently co-transfected with empty vector and NDUFB5-MYC, or OMA1-E324Q-Flag and NDUFB5-MYC. Cell lysates were used for co-immunoprecipitation with anti-Flag M2 affinity gel at 4°C overnight, followed by Western blotting with anti-Flag or anti-MYC antibodies (n = 3 independent experiments).",
    "ncbi_link": "Flag: 
MYC: 
NDUFB5: 4711
OMA1: 115209"
  },
  {
    "caption": "B. 293T cells were transiently co-transfected with empty vector and NDUFB6-GFP, or OMA1-E324Q-Flag and NDUFB6-GFP. Cell lysates were used for co-immunoprecipitation with anti-Flag M2 affinity gel at 4°C overnight, followed by Western blotting with antibodies against Flag or GFP (n = 3 independent experiments).",
    "ncbi_link": "Flag: 
GFP: 
GFP.: 
NDUFB6: 4712
OMA1: 115209"
  },
  {
    "caption": "C. 293T cells were transiently co-transfected with empty vector and COX4L1-GFP, or OMA1-E324Q-Flag and COX4L1-GFP. Cell lysates were used for coimmunoprecipitation with anti-Flag M2 affinity gel at 4°C overnight, followed by Western blotting with anti-Flag or anti-GFP antibodies (n = 3 independent experiments).",
    "ncbi_link": "Flag: 
GFP: 
GFP.: 
COX4L1: 1327
OMA1: 115209"
  },
  {
    "caption": "D. 293T cells were transiently co-transfected with empty vector and NDUFA4-GFP, or OMA1-E324Q-Flag and NDUFA4-GFP. Cell lysates were used for coimmunoprecipitation with anti-Flag M2 affinity gel at 4°C overnight, followed by Western blotting with antibodies against Flag or GFP (n = 3 independent experiments).",
    "ncbi_link": "Flag: 
GFP: 
GFP.: 
NDUFA4: 4697
OMA1: 115209"
  },
  {
    "caption": "E. HCT116 cells stably expressing control (empty vector) or OMA1-Flag, and HCT116 cells infected with control or shOMA1 (OMA1 knockdown) lentiviral particles and further cultured for 5 days, were then treated with DMSO or 20 μm CCCP for 4 hours. Cell lysates were analyzed by Western blotting with antibodies against NDUFA4, COX4L1, NDUFB5, DNUFB6, MT-CO2, OMA1 or Tubulin. The black arrowhead indicated the full-length COX4L1 or NDUFB6, and the red arrowhead pointed to the cleaved band. The asterisk indicates a nonspecific band.",
    "ncbi_link": "Flag: 
OMA1: 115209"
  },
  {
    "caption": "F. WT, OMA1 KO and OMA1 KO HCT116 cells expressing WT-OMA1(OMA1-Flag) or proteolytic inactive OMA1(E324Q-Flag) were treated with CHX (100 µg/ml) plus CCCP (20 µM) for 0, 2, 4, 6 hours. The cell lysates were then assessed by western blot with antibodies against NDUFA4, COX4L1, NDUFB5, NDUFB6, OMA1 or HSPD1 (representative data from three independent experiments). The asterisk indicates a nonspecific band.",
    "ncbi_link": "Flag: 
OMA1: 115209"
  },
  {
    "caption": "G. Control or OMA1 KO HCT116 cells were cultured in hypoxia (1% O2) for 0, 24, or 48 hours. Cell lysates were assessed by Western blotting with anti-NDUFB5, anti-NDUFB6, anti-COX4L1, anti-NDUFA4 antibodies, or anti-β-Actin. The relative protein levels were further evaluated by densitometry analysis using ImageJ software and were presented as bar graphs in the right panels. Error bars are presented as mean ± SD by a two-way ANOVA (n = 3 independent experiments). *p<0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "A. Mitochondria isolated from tumors (T) or adjacent normal (N) tissues of WT and OMA1-/- mice were subjected to blue native PAGE (BN-PAGE), and respiratory chain complexes were analyzed by Western blotting with anti-NDUFB8 (Complex I), anti-SDHA (Complex II), anti-COX4L1 (Complex IV), and anti-ATP5A1 (Complex V, ATP synthase) antibodies. SDS-PAGE with antibody against HSPD1 was used as a loading control. Relative protein levels were further evaluated by densitometry analysis using ImageJ software. Error bars are presented as mean ± SD by a two-way ANOVA (n = 3 independent experiments). *p<0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "B. Digitonin-solubilized mitochondria were isolated from control and OMA1 KO HCT116 cells cultured in normoxia or hypoxia (1% O2) for 12 hours, and then analyzed by BN-PAGE and immunoblotting using the indicated antibodies against NDUFB8 (Complex I), SDHA (Complex II), NDUFA4 (Complex IV), and ATP5A1 (Complex V). SDS-PAGE with antibody against HSPD1 was used as a loading control. Relative protein levels were further evaluated by densitometry analysis using ImageJ software. Error bars are presented as mean ± SD by a two-way ANOVA (n = 3 independent experiments). N.S., not significant, *p<0.05.",
    "ncbi_link": "OMA1: 115209"
  },
  {
    "caption": "C. The lysates of adjacent normal tissues (N) or tumors (T) from WT and OMA1-/- mice were analyzed by Western blotting with antibodies against NDUFA4, COX4L1, NDUFB5, DNUFB6, UQCRC2, or Tubulin. Relative protein levels were further evaluated using ImageJ software. Error bars indicate the mean ± SD by a two-way ANOVA (n = 3 independent experiments). *p<0.05, ***p < 0.001.",
    "ncbi_link": "OMA1: 67013"
  },
  {
    "caption": "A. Immunoblot  analysis of ACE2 expression  in the lysate of human lung A549  cells overexpressing ACE2  compared to non-transduced (-) A549  cells. Calnexin served as loading control.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "B, C. Illustration of the Incucyte readout. Infection of A549  or ACE2-expressing A549  cells with  SARS-CoV-2 encoding a GFP  expression cassette. Infection  of cells was monitored microscopically  as green fluorescence through  live-cell imaging at 24 hours post infection  (hpi) (B) or during the  time-course  of 48 h and shown as the mean of the GFP-positive area relative to the whole area covered by cells in the same well (C). Error bars represent means ± SD derived from biological triplicates (N = 3). Scale bar, 500 µm.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "D. A549-ACE2  cells were treated for 6 hours with different concentrations of indicated inhibitors and then infected with SARS-CoV-2-GFP. GFP-fluorescence relative to DMSO-treated control cells was determined 48 hpi as described in (C). Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed for every indicated concentration compared to DMSO  (0 µM). Asterisks indicate significance compared to DMSO  (N = 3-6). Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "E. A549-ACE2  cells were treated for 30 min with PMA  at indicated concentrations and then infected with SARS-CoV-2-GFP. Infection  of cells was monitored as in C. Two-way ANOVA with Tukey's post-hoc multiple comparison test. Asterisks indicate significance compared to the DMSO  control of each time point  (N = 9). Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "F, A549-ACE2  cells were treated with apratastat, DPC-333 at indicated concentrations. Experiment was conducted and analyzed as in (D). Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed for every indicated concentration compared to DMSO  (0 µM). Asterisks indicate significance compared to DMSO  (N = 3-6). Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "G. A549-ACE2  cells were treated with apratastat, DPC-333 or BB94  at indicated concentrations. Experiment was conducted and analyzed as in (D). Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed for every indicated concentration compared to DMSO (0 µM). Asterisks indicate significance compared to DMSO  (N = 3-6). Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "H, I. A549-ACE2  cells were treated for 1 h with indicated inhibitors (10 µM) or DMSO  before inoculation with GFP-encoding spike  pseudoparticles (VSV  pseudotyped with  SARS-CoV-2 spike  protein (VSV-S)) (H) or as a control LCMV glycoprotein  (VSV-GP) (I). At 16 hpi, infection  was analyzed by counting GFP-positive cells. Data are normalized to the number of infected cells in virus-only control wells without DMSO  (N = 3-5). One-way ANOVA with Tukey's post-hoc multiple comparison test. Asterisks indicate significance compared to DMSO. Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "GFP: 
ACE2: 59272"
  },
  {
    "caption": "A, RT-qPCR quantification of  viral RNA (SARS-CoV-2 N gene  relative to RPLP0) upon infection  of A549-ACE2  cells with indicated SARS-CoV-2 strains at 24 hpi. Cells were pretreated with BB94  (10 µM) or DMSO  for 6 h. Data are normalized to DMSO  (N = 3-7). A two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed. Data information: Data are represented as means ± 95% CI from at least three (A, biological replicates *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272
N gene: 43740575
RPLP0: 6175"
  },
  {
    "caption": "B.  RT-qPCR  quantification of  viral RNA  (SARS-CoV-2 N gene relative to RPLP0) upon infection  of A549-ACE2  cells with indicated  SARS-CoV-2 strains at 24 hpi. Cells were pretreated with BB94  (10 µM), DPC-333 (10 µM) or DMSO  for 6 h. Data are normalized to DMSO (N = 3-7). A two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed. Data information: Data are represented as means ± 95% CI from at least three , B) biological replicates *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272
N gene: 43740575
RPLP0: 6175"
  },
  {
    "caption": "C. Normal Human Bronchial Epithelial cells (NHBE) from ten donors were infected with SARS-CoV-2. NHBE   cells were pre-treated with camostat mesylate (10µM), BB94  (1 µM or 10 µM) or DMSO  for 6 hours. RNA was isolated at 24 hpi and levels of SARS-CoV-2 N relative to RPLP0  from total cellular RNA was measured by RT-qPCR. Data are normalized to the DMSO  control (N = 5-10). Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction. Data information: Data are represented as means ± 95% CI from at least five/ten biological replicates *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "RPLP0: 6175"
  },
  {
    "caption": "A. Western Blot (WB) analysis of A549-ACE2  knock-out (KO) lines. Two different KO lines were generated using distinct CRISPR  guide RNAs for both ADAM10  and ADAM17. A non-targeting control (NTC) guide RNA served as control. Shown are two replicates for each cell line. Mature (m) and immature (im) forms of ADAM10  and ADAM17  are indicated. ACE2  levels remained unaffected.  α-tubulin  served as loading control. *: remaining, low amount of immature ADAM10  and ADAM17. The double KO (dKO) was generated from guide 1 of each ADAM10  and ADAM17. B. Quantification of the abundance of mature ADAM10  and ADAM17  protein forms from (A). Data are normalized to loading control tubulin  and to NTC (N = 3-4). The band of mADAM17 runs very close to three unspecific bands (marked with arrowheads) - one closely above and two closely below mADAM17 (A). Thus, quantification of remaining mADAM17 in the ADAM10  KO includes also these three unspecific bands. Two-sided independent Student's t-test with Benjamini-Hochberg FDR correction. Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "CRISPR: 
ACE2: 59272
ADAM10: 102
ADAM17: 6868"
  },
  {
    "caption": "C. RT-qPCR  quantification of viral RNA (SARS-CoV-2 N gene relative to RPLP0) upon infection  of A549-ACE2  NTC or KO cells with SARS-CoV-2. Cells were treated with BB94  (10 µM) or DMSO  for 6 h prior to infection  and RNA was isolated at 24 hpi. Two-way ANOVA with Tukey's post-hoc multiple comparison test. Data are normalized to NTC DMSO  (N = 3). Data information: Data are represented as means ± 95% CI from at least three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272
N gene: 43740575
RPLP0: 6175"
  },
  {
    "caption": "D-G. UMAP of 63,103 cells from BAL fluid  derived from infected individuals (D) Individual cell types are indicated in color. (E) Normalized counts of SARS-CoV-2 reads, ADAM10, ADAM17, and TMPRSS2 gene expression levels. (F) Dot plot of ADAM10, ADAM17, and TMPRSS2  expression, grouped by disease severity. Expression levels are color-coded, the percentage of cells expressing the aforementioned genes is size coded. (G) Cells that are infected and additionally express ADAM17  (ADAM17+, red), ADAM10  (ADAM10+, blue), both ADAMs (ADAM10+ ADAM17+, purple), or TMPRSS2  (TMPRSS2+, orange) are indicated.",
    "ncbi_link": "ADAM10: 102
ADAM17: 6868
TMPRSS2: 7113"
  },
  {
    "caption": "B. Representative images of syncytia  formation assay. Large syncytia  were observed for NTC and ADAM17  KO cells, but were strongly reduced when ADAM10  was knocked-out, either alone or together with ADAM17  or upon inhibition with BB94  (10 µM). For both ADAMs, the cell lines obtained with gRNA sequence 1 were used. Images show GFP  fluorescence and Hoechst staining. Scale bars, 50 µm. C. Quantification of images from fluorescence microscopy (B). Left plot: the area of the fused cells in green (GFP) was quantified and normalized to the Hoechst  signal (blue) of the entire image to account for differences in cell density. Right plot: The nuclei  within syncytia  were determined by calculating the ratio between the Hoechst  signal within syncytia  and the total Hoechst  signal in the entire image. The data are normalized to NTC DMSO  (N >= 8). Two-way ANOVA with Tukey's correction for multiple comparisons. All data are represented as means ± 95% CI of at least 3 independent experiments. **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ADAM10: 102
ADAM17: 6868"
  },
  {
    "caption": "C. Representative images and quantification of a proximity ligation assay  (PLA) between the SARS-CoV-2 Spike  and ADAM17  in A549-ACE2  cells. Cells were infected with SARS-CoV-2 and placed on ice (4°C). After 2 h, cells were shifted to 37°C for 15 min or left on ice. Images are presented as overlay between the Nuclei  (Hoechst, blue) and the PLA  (pseudo-color: red) channel. Scale bar, 20 µm. The number of PLA  foci per cell was determined for the acquired images (N = 28-30). A two-sided independent Student's t-test with Benjamini-Hochberg FDR correction was performed. Data information: Data are represented as means ± 95% CI of at least 3 independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "D. A549-ACE2  cells were treated for 48 h with BB94  (10 µM), DPC-333 (5 µM) or DMSO. PMA  (25 ng/ml) was added for 3 h before harvest to stimulate ACE2   shedding. Concentration of the soluble ACE2  fragment was determined in the conditioned medium by ELISA  and is shown relative to the concentration in the DMSO  control (N = 6). One-way ANOVA with Tukey's post-hoc multiple comparison test. Data information: Data are represented as means ± 95% CI of at least 3 independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "E. GFP-encoding spike  pseudoparticles (VSV  pseudotyped with SARS-CoV-2 spike protein (VSV-S) were incubated with indicated amounts of recombinant, soluble ACE2 (sACE2) or  bovine serum albumin (BSA) as a control prior to infection  of A549-ACE2  cells. At 16 hpi, infection  was analyzed by counting GFP-positive cells. Data are normalized to the number of infected cells in virus-only control wells without sACE2  or BSA  (N = 3). Two-sided independent Student's t test with Benjamini-Hochberg FDR correction. Data information: Data are represented as means ± 95% CI of at least 3 independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "GFP: 
ACE2: 59272"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from ARPE-19 cells expressing TFEB-WT-FLAG  or TFEB-S401A-FLAG  treated with 200 μM NaAsO2  or 250 nM Torin-1  for 1 h. Two different rabbit polyclonal antibodies raised against a TFEB-S401 phospho-specific peptide were tested.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from  ARPE-19 cells expressing TFEB-WT-FLAG, TFEB-S3A/R4A-FLAG  or TFEB-R245-247A-FLAG  treated with 200 μM NaAsO2  for 1 h. Immunoblots  are representative of at least three independent experiments.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from HeLa  cells stably expressing TFEB-WT-FLAG  incubated with the indicated kinase inhibitors for 1 h prior to the addition of 200 μM NaAsO2  for 1 h. Quantification of immunoblot  data shown in (A). Data are presented as mean ± SD using one-way ANOVA (unpaired) followed by Tukey's multiple comparisons test, (ns) not significant, and (****)p<0.0001 from three independent experiments. Data information: n = 3 biological replicates (each dot represents a biological replicate).",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from HeLa   cells stably expressing TFEB-WT-FLAG  incubated with either 200 μM NaAsO2  for 1 h, EBSS  for 4 h, 100 ng/ml EGF   for the indicated times  or 37 μM Anisomycin  for 1 h. Before the addition of EGF  or Anisomycin, cells were serum  starved for 8 h.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from HeLa  cells stably expressing TFEB-WT-FLAG  exposed to 30J/m2 of UV-C and allowed to recover in complete medium for the indicated times. Cells were incubated with p38 MAPK inhibitor (20 μM, SB203580) for 1 h before  UV-C irradiation  and allowed to recover for 30 min in the presence of the inhibitor.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from HeLa  cells stably expressing TFEB-WT-FLAG  depleted of either p38 MAPK (α+β) or JNK1  or JNK2  or JNK(1+2) and incubated with 200 μM NaAsO2  for 1 h. Immunoblots  are representative of at least three independent experiments.",
    "ncbi_link": "FLAG: 
JNK1: 5599
JNK2: 5601
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from Raw 264.7  cells stably expressing TFEB-WT-FLAG  incubated with 1μg/ml LPS  for the indicated times.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from  Raw 264.7 cells stably expressing TFEB-WT-FLAG  incubated with either 20 μM SB203580  or 250 nM Torin-1 for 1 h prior to the addition of 1 μg/ml LPS  for 30 min.",
    "ncbi_link": "FLAG: 
TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates from naïve THP1-WT or TFEB-S401A knock-in (clone M17) cells treated with 50 ng/ml PMA  for the indicated times, PMA-differentiated THP1  (Rested) cells treated without or with 250 nM Torin-1  for 1 h.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of proteins from nuclear  and cytosolic  fractions from naïve THP1-WT or TFEB-S401A knock-ins (clones I11 and M17) cells treated with 50 ng/ml PMA  for the indicated times  and PMA-differentiated THP1  (Rested) cells.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of proteins from nuclear  and cytosolic  fractions from naïve THP1-WT or TFEB-S401A knock-in (clone I11) cells treated with 50 ng/ml PMA  for the indicated times.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of proteins from nuclear  fractions from naïve THP1-WT or TFEB-S401A knock-in (clone I11) cells treated with 50 ng/ml PMA or 250 nM  Torin-1 for 1 h. Immunoblots  are representative of at least three independent experiments.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of proteins from nuclear  and cytosolic  fractions from naïve THP1-WT or TFEB-S401A knock-in (clone I11) cells treated with 50 ng/ml PMA  for 6 h.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Immunoblot  analysis of protein lysates   and cell culture medium from PMA-differentiated (Rested) THP1-WT or TFEB-S401A knock-ins (clones I11 and M17) cells incubated with 0.1 μg/ml LPS  for 4 h prior to the addition of 15 μM Nigericin  for 45 min. C-F. Quantification of immunoblot  data shown in (B). Data are presented as mean ± SD using one-way ANOVA (unpaired) followed by Tukey's multiple comparisons test, (ns) not significant, (*)p<0.05, (**)p<0.01, (***)p< 0.001 and (****)p< 0.0001 from three independent experiments. Data information: n ≥ 3 biological replicates (each dot represents a biological replicate).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Fluorescence confocal microscopy of PMA-differentiated (Rested) THP1-WT or TFEB-S401A knock-ins (clones I11 and M17) cells incubated with 1 μg/ml LPS  for 6 h prior to the detection of dead cells with LIVE/DEAD fixable blue dead cell stain. Scale bars, 10 μm. Quantification of the  percentage of dead cells shown in (G). Data are presented as mean ± SD using one-way ANOVA (unpaired) followed by Tukey's multiple comparisons test, (ns) not significant and (****)p< 0.0001 as compared to their corresponding untreated (Control) cells, with >200 cells counted per trial from three independent experiments. Data information: n ≥ 3 biological replicates (each dot represents a biological replicate).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Double-immunolabeling of Sororin (green) and SYCP3 (red), and counterstaining of the chromatin with DAPI (blue) on spread Sgo2-/- spermatocytes at (A) pachytene (Pac.), (B) diplotene (Dip.), (C) metaphase I (M I), and (D) metaphase II-like (M II-like). The sex bivalent (XY) is indicated. Arrowheads indicate round bodies. Arrows in (A) indicate the pseudoautomal region in the sex bivalent, and the centriolar area at cell poles in (C,D). Scale bar: 10 µm.",
    "ncbi_link": "Sgo2: 244495///68549"
  },
  {
    "caption": "Double-immunolabeling of Sororin (green) and SYCP3 (red) on spread cultured wild-type control (WT Control), and okadaic acid treated wild-type (WT + OA) and Smc1β-/- (Smc1β-/- + OA) spermatocytes.A-B WT control cultured spermatocytes in (A) late zygotene (L. zyg.) and (B) metaphase I (M I). Arrows indicate the cell poles.C-D WT cultured spermatocytes treated with okadaic acid in (C) late zygotene (L. zyg.) and (D) metaphase I-like (M I-like).E-F Smc1β-/- cultured spermatocytes treated with okadaic acid in (E) pachytene-like (Pac.-like) and (F) metaphase I-like (M I-like). Arrowheads indicate nucleolar-associated round bodies. The unsynapsed axial elements of the sex chromosomes (X,Y) in prophase I, as well as the sex bivalent (XY) in metaphases I are indicated. Scale bar: 10 µm.",
    "ncbi_link": "Smc1β: 140557"
  },
  {
    "caption": "Co-staining of P28 and GAP45 (IMC protein) in female gametes (P28+ only) and zygotes (P28+/GAP45+) of the 17XNL, Δap2-o3 and Δcdpk4 strains. Percentages of female gametes and zygotes were indicated respectively. n is the number of cells counted. Scale bars = 5 μm. Note: the signal of P28 and GAP45 is reduced similarly in all Δap2-o3 female gametes and zygotes compared to that of 17XNL.",
    "ncbi_link": "cdpk4: 3830518
ap2-o3: 3791637"
  },
  {
    "caption": "Day 7 midgut oocyst counts from mosquitoes infected with parasites, including 17XNL, Δap2-o3, Δmap2, or Δnek4 strain alone as well as mixtures of Δmap2/Δnek4, Δap2-o3/Δmap2, and Δap2-o3/Δnek4. Δnek4 and Δmap2 are female and male gamete-defect parasites, respectively. n is the number of mosquitoes dissected, Mann-Whitney test applied, two experiments repeated.",
    "ncbi_link": "nek4: 3829560
map2: 3791836
ap2-o3: 3791637"
  },
  {
    "caption": "Transcript expression heatmap by RNA-seq of 26 genes involving DNA replication and DNA repair between DFsc7 (WT) and DFsc7;Δap2-o3 (KO) strains.",
    "ncbi_link": "ap2-o3: 3791637"
  },
  {
    "caption": "Representative fluorescence microscopy images of mCherry and DPOD2::GFP expression in female and male gametocytes of the DTS1 (ccp2::mCherry;dpod2::gfp) and DTS1;Δap2-o3 strains. mCherry is specifically expressed in female gametocytes. Flow cytometry detection of mCherry and DPOD2::GFP expression in female and male gametocytes of the DTS1 and DTS1;Δap2-o3 strains. The female and male gametocyte populations are circled by solid and dashed line respectively. E,F Similar analysis (as in C, D) in DTS2 (ccp2::mCherry;dpod1::gfp) and DTS2;Δap2-o3 strains. G,H Similar analysis (as in C, D) in DTS3 (ccp2::mCherry;rpa1::gfp) and DTS3;Δap2-o3 strains. I,J Similar analysis (as in C, D) in DTS4 (ccp2::mCherry;mcm7::gfp) and DTS4;Δap2-o3 strains.",
    "ncbi_link": "ccp2: 
gfp: 
mCherry: 
dpod2: 3807075
rpa1: 3790834
dpod1: 3807142
mcm7: 3830453
ap2-o3: 3791637"
  },
  {
    "caption": "EMSA using the recombinant GST-fused AP2 domain of AP2-O3 and a synthesized DNA probe containing three repeats of predicted motif. GST was used as a negative control. An arrowhead indicates the shifted band.",
    "ncbi_link": "AP2-O3: "
  },
  {
    "caption": "Western blot of GAP45 protein expression in non-activated (NAG) and activated gametocyte (AG) of 17XNL and Δap2-o3 strains. BiP as loading control.",
    "ncbi_link": "ap2-o3: 3791637"
  },
  {
    "caption": "IFA of AP2-O3 protein expression in activated gametocytes of Pccp2 strains.",
    "ncbi_link": "ccp2: "
  },
  {
    "caption": "(b) Estimation of gene editing at the Trim28 loci using NGS-sequencing of amplicons. Black bars indicate % of frameshift indels. Columns show an average of two biological replicates per guide RNA and error bars show mean ± SD.",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " (c) Western blot confirmed the loss of Trim28 expression upon Trim28-KO in mouse NPCs. ",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " (d) RNA-seq analysis of the expression of TE-families using TEtranscripts (e) The significantly upregulated TE families with a fold change larger than 0.5 upon Trim28-KO in mouse NPCs. The dashed line indicates significance. ",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " (f) CUT&RUN analysis of H3K9me3 in mouse NPCs of all full length MMERVK10Cs (right panel) RNA-seq analysis of the Trim28-KO and control samples, visualising full length MMERVK10C elements. The location of the full length MMERVK10Cs are indicated as a thick black line under each histogram. ",
    "ncbi_link": "MMERVK10C: 
MMERVK10Cs: 
Trim28: 21849"
  },
  {
    "caption": " (g) Example of transcriptional readthrough outside the full length MMERVK10Cs into a nearby gene. ",
    "ncbi_link": "MMERVK10Cs: "
  },
  {
    "caption": " (b) Estimation of gene editing at the Trim28 loci using NGS-sequencing of amplicons from DNA isolated from 50.000 RFP+ nuclei per animal. One animal per group was analyzed. Black bars indicate % of the detected indels that disrupted the frameshift. ",
    "ncbi_link": "RFP: 
Trim28: 21849"
  },
  {
    "caption": " Gene editing of the Trim28-loci resulted in a robust loss of Trim28 protein, as evaluated by IHC where the expression of Trim28 in RFP+ cells were quantified and are displayed as mean ± SEM. Approximately 600 RFP+ cells per animal and group was evaluated. Scale bar 30 μm. ",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " Gene editing of the Trim28-loci resulted in a robust loss of Trim28 protein, as evaluated by IHC where the expression of Trim28 in RFP+ cells were quantified and are displayed as mean ± SEM. Approximately 600 RFP+ cells per animal and group was evaluated. Scale bar 30 μm. ",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " (f) RNA-seq analysis of the Trim28-KO and control samples, visualising full length MMERVK10C elements (left panel) and ChIP-seq analysis of H3K9me3 in adult forebrain neurons (right panel). The location of the full length MMERVK10Cs are indicated as a thick black line under each histogram. ",
    "ncbi_link": "MMERVK10C: 
MMERVK10Cs: 
Trim28: 21849"
  },
  {
    "caption": "(b) IHC for Trim28 in the adult cortex revealed that the protein was lost in cells exposed to Cre-activity during brain development (GFP+ cells). Scale bars: low magnification 75 μm, high magnification 20μm.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": " (c) RNA-seq analysis of the expression of TE-families using TEtranscripts (d) Significantly upregulated TE families upon the Trim28-KO, in which the families with the highest fold change are listed. ",
    "ncbi_link": "Trim28: 21849"
  },
  {
    "caption": " (e) RNA-seq analysis of full length MMERVK10Cs in the adult tissue. The location of the full length MMERVK10Cs are indicated as a thick black line under each histogram. ",
    "ncbi_link": "MMERVK10Cs: "
  },
  {
    "caption": " (e-h) A selection of significant cell type specific changes in gene expression between Emx1-Cre/Trim28-KO animals and controls as revealed by single-nuclei RNA-seq. The black dots represent the mean value value (Wilcoxon rank sum test, (p-adj value < 0.01), n=2. ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": " (b) Mean plots show the changes of TE subfamily expression in each cell cluster upon the Emx1-Cre/Trim28-KO. A differential expression analysis performed with DESeq2 (described in material and methods) showed upregulated TEs in cell types in which Trim28 was deleted (excitatory neurons, astrocytes, oligodendrocytes and oligodendrocyte precursors), (indicated with red dots: p-adj < 0.01, log2FC > 3). The specific upregulated elements and their fold changes are listed in bar graphs under each mean plot. In cell types in which Trim28 was not deleted, TE expression remained unaffected (inhibitory neurons and microglia). ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": " (a) IHC analysis for the microglia marker Iba1 in Emx1-Cre/Trim28-KO animals and controls. Scale bars: Low magnification 75 μm, high magnification 10 μm. (b-c) The morphology of microglia in cortex and striatum (control region) of Emx1-Cre/Trim28-KO animals and controls were quantified by high content screening of Iba1 immunoreactivity, revealing differences in process length, area and number of branch points specifically in cortex, error bars mean ± SEM (unpaired t-test. p-values: 1.8x10-4, 9.6x10-4 and 5.2x10-6, respectively). A large number of photos from three control and two KO animals were analysed ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": " (d) Western blot revealed an increased expression of CD68 in the Emx1-Cre/Trim28-KO animals (n=5 per group), unpaired t-test, **p=0.0036, error bars mean ± SEM. The star indicates an unspecific band. ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": " (e) An increased expression of the ERV derived protein IAP-Gag was detected in the cortex of Emx1-Cre/Trim28-KO animals (n=5 per group), unpaired t-test, ***p=0.0008, error bars mean ± SEM. ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": " (f) Immunohistochemistry for IAP-gag visualized the presence of ERV proteins in the cortex of Emx1-Cre/Trim28-KO animals. The distribution of IAP-gag was heterogenous among Trim28-KO neurons, where it was either accumulated in a low (#) or high (°) number of aggregate-like structures in the cytoplasm, or as weak homogenous staining throughout the cytoplasm (#) or not present at all (*). Scale bars: low magnification 75μm, high magnification 5 μm. ",
    "ncbi_link": "Emx1: 13796
Cre: 2777477
Trim28: 21849"
  },
  {
    "caption": "Electron microscopy revealed a number of demyelinated or degenerated axons in PLP-150Q mice at the age of 5 months. LAQ (5 mg/kg) treatment at 3 months of age for 2 months improved myelination in PLP-150Q mice. Scale bars: 2μm (Low magnification) and 0.5 μm (High magnification).",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "G-ratios, which were calculated and plotted against axon diameter with linear regression, were shown beneath the micrographs and were significantly decreased in PLP-150Q mice after LAQ treatment (G=0.6418±0.0191), compared with age-matched vehicle group (G=0.7727±0.0203). One-way ANOVA with Tukey's test. *P=0.0166. At least 182 axons per genotype were examined from 3 mice in each group.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Western blotting showing that LAQ (5 or 25 mg/kg) treatment for 2 months up-regulates multiple myelin proteins (MBP, MOBP and MOG) in the corpus callosum in PLP-150Q mice, which were treated from 3 months of age. Ratios of MBP, MOBP or MOG to vinculin obtained from 3 independent experiments were presented on the right. One-way ANNOVA followed with Tukey's test. MBP: ***P=0.0009; MOG: ***P=0.0003; MOBP: **P=0.0067. Data are mean ±SEM",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Quantitative PCR of the transcript expression of myelin associated genes (MBP and MOG) in PLP-150Q mouse corpus callosum at 5 months of age after LAQ (5 or 25 mg/kg) treatment for 2 months. Student's t-test. MBP: ***P=0.0007; MOG: ***P=0.0009. Data are mean ±SEM (n=3).",
    "ncbi_link": "MBP: 17196
MOG: 17441
PLP: 18823"
  },
  {
    "caption": "The MBP DNA promoter was inserted into the pGL4.1 luciferase report vector and was co-expressed with N-terminal MYRF (nMYRF) and mHTT to assess its transcription activity via the luciferase assay. MYRF markedly enhanced the MBP promoter activity. N-terminal mutant HTT significantly inhibited the reporter activity, ***P< 0.001; which was reversed by LAQ (5 μM) treatment, **P< 0.01. The ratios were obtained from 3 independent experiments. One-way ANNOVA followed with Tukey's test. Data are mean ±SEM.",
    "ncbi_link": "luciferase: 
HTT: 3064
MBP: 17196
MYRF: 225908"
  },
  {
    "caption": "Immunoprecipitation of transgenic mHTT from 3-month-old PLP-150Q mouse brains revealed that 5 or 25 mg/kg LAQ treatments for 2 months reduced the interaction between transgenic mutant HTT and MYRF. fMYRF: full-length MYRF; nMYRF: N-terminal MYRF. The ratio of immunoprecipitated MYRF to input obtained from 3 independent experiments was shown on the right. One-way ANNOVA followed with Tukey's test. **P=0.009. Data are mean ±SEM.",
    "ncbi_link": "HTT: 3064
PLP: 18823"
  },
  {
    "caption": "Western blotting of the phosphorylated- NF-kB, -Akt, -JNK in PLP-150Q mouse corpus callosum at 3 months of age showing that LAQ (5 or 25 mg/kg) treatment for 2 months could dephosphorylate these proteins. Ratios of the phosphorylated proteins to their total proteins obtained from 3 independent experiments were presented on the right. One-way ANNOVA with Tukey's test. NF-kB: ***P=0.00067(left) and 0.00086(right); JNK: ***P=0.00013(left) and 0.00047(right); Akt: **P=0.0014 and ***P=0.00012. Data are mean ±SEM.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "In vitro phosphorylation assay of N-terminal MYRF (nMYRF). GST fusion proteins containing nMYRF were incubated overnight with brain lysates from PLP-23Q or PLP-150Q mice that were treated with vehicle or 5 mg/kg LAQ (left panel). GST fusion proteins containing wild type N-terminal MYRF, S259A, or S261A were incubated with PLP-150Q mouse tissue lysates (right panel). The beads were then centrifuged and analyzed by western blotting with anti-GST (lower panels) and anti-phosphor-serine (upper panels). Note that LAQ treatment could eliminate mutant HTT (PLP-150Q)-mediated MYRF phosphorylation and that S259A substitution prevents MYRF phosphorylation.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Co-transfection of nMYRF with N-terminal mutant HTT in HEK293 cells and immunoprecipitation of nMYRF with or without LAQ (5 μM) treatment. Coomassie blue staining confirms the presence of immunoprecipitated N-terminal MYRF bands (arrow).",
    "ncbi_link": "HTT: 3064
MYRF: 225908"
  },
  {
    "caption": "Transcriptional activity of wide type N-terminal MYRF, S259A, or S261A with the MBP promoter reporter in HEK293 cells was detected using a luciferase assay. Compared to wide type MYRF or S261A, S259A (non-phosphorylated) remained transcriptional activity that was not inhibited by N-terminal mutant HTT. The ratios were obtained from 3 independent experiments. One-way ANNOVA with Tukey's test. ***P< 0.001. Data are mean ±SEM.",
    "ncbi_link": "HTT: 3064
MBP: 17196
MYRF: 225908"
  },
  {
    "caption": "Co-transfection of wide type N-terminal MYRF, S259A, or S261A with N-terminal mutant HTT in HEK293 cells and immunoprecipitation of MYRF. Compared to wide type MYRF and S261A, less S259A (non-phosphorylated) was precipitated with mutant HTT. The ratios of the pho-serine MYRF or precipitated HTT to immunoprecipitated MYRF are shown under the blots and were obtained from 3 independent experiments. One-way ANNOVA with Tukey's test. ***P=2.30x10-5 . Data are mean ±SEM.",
    "ncbi_link": "HTT: 3064
MYRF: 225908"
  },
  {
    "caption": "Western blotting analysis of the corpus callosum in PLP-23Q or PLP-150Q mice with anti-pS259 and an antibody to total MYRF. Note that LAQ (5 mg/kg) treatment for 2 months decreased the phosphorylation in both full length (fMYRF) and N-terminal MYRF (nMYRF) in PLP-150Q mice.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Anti-Ser259-MYRF immunohistochemical staining of the corpus callosum (CC, indicated between two dotted lines) of PLP-23Q and PLP-150Q mice showing decreased expression of Ser259-MYRF by LAQ (5 mg/kg) treatment for 2 months. Micrographs at 10X (upper) and 40X (lower) are shown. Scale bars: 40 μm.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Heatmaps of gene expression in PLP-150Q mouse corpus callosum at 5 months after LAQ (5 mg/kg) treatment for 2 months revealed 27 significantly upregulated and 103 significantly downregulated genes.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Western blotting showing down-regulation of PRKG2 in PLP-150Q mouse corpus callosum at 3 months of age by 5 mg/kg LAQ. Ratios of PRKG2 or phosphorylated VASP (p-VASP) to GAPDH obtained from 3 independent experiments were presented on the right. One-way ANNOVA with Tukey's test. PRKG2: **P=0.0076(left) and ***P=0.0015(right); p-VASP: ***P=3.86x10-5(left) and 1.01x10-5(right). Data are mean ±SEM.",
    "ncbi_link": "PLP: 18823"
  },
  {
    "caption": "Quantitative PCR of PRKG2 or PRKG1 gene expression in PLP-150Q mouse corpus callosum at 5 months of age after LAQ (5 mg/kg) treatment for 2 months. Only PRKG2 was decreased by LAQ. n=3 mice in each group. Student's t-test; **P=0.0073; ***P=0.00041. Data are mean ±SEM.",
    "ncbi_link": "PLP: 18823
PRKG1: 19091
PRKG2: 19092"
  },
  {
    "caption": "The different PRKG2 promoter regions were inserted into the pGL4.1 luciferase report vector. The core promoter reporter vector of PRKG2 (-472/+131) was determined for transcription activity in cultured N2a cells, obtained from 3 independent experiments. One-way ANNOVA with Tukey's test; ***P<0.001. Data are mean ±SEM.",
    "ncbi_link": "luciferase: 
PRKG2: 19092"
  },
  {
    "caption": "The treatment of LAQ (5 or 10 μM) caused a marked inhibition on the transcription activity of the PRKG2 promoter detected by the luciferase assay from 3 independent experiments. One-way ANNOVA with Tukey's test. ***P<0.001. Data are mean ±SEM.",
    "ncbi_link": "luciferase: 
PRKG2: 19092"
  },
  {
    "caption": "The qPCR analysis of the transcripts of Cyp1a1 and Ugt1a6a, which were mediated by AhR, in the PLP-150Q mouse brain (corpus callosum). Note that Cyp1a1 and Ugt1a6a were significantly increased by LAQ (5 mg/kg). n=3 mice in each group. Student's t-test; Cyp1a1: ***P=0.00042; Ugt1a6a; ***P=0.00057. Data are mean ±SEM.",
    "ncbi_link": "AhR: 11622
Cyp1a1: 13076
PLP: 18823
Ugt1a6a: 94284"
  },
  {
    "caption": "The PRKG2 core promoter activity in N2a cells transfected with AhR siRNA or its scrambled siRNA control and then treated with 5 μM LAQ. The values of promoter activity via luciferase report assay were obtained from three independent experiments. One-way ANNOVA with Tukey's test. ***P< 0.001. Data are mean ±SEM.",
    "ncbi_link": "AhR: 11622
PRKG2: 19092"
  },
  {
    "caption": "The semi-PCR detection of PRKG2 promoter DNAs associated with AhR that was immunoprecipitated by anti-AhR in ChIP assay. The N2a cells were treated with 10 μM LAQ or 10 nM 2,3,7,8-TCDD or DMSO for 12 hr. The quantification of PRKG2 promoter DNAs associated with AhR that was immunoprecipitated by anti-AhR in ChIP assay. The N2a cells were treated with 10 μM LAQ or 10 nM 2,3,7,8-TCDD or DMSO for 12 hr. The results were obtained from three independent experiments. One-way ANNOVA with Tukey's test. LAQ: ***P=0.00065; 2,3,7,8-TCDD: ***P=0.00014. Data are mean ±SEM",
    "ncbi_link": "PRKG2: 19092"
  },
  {
    "caption": "Western blotting showing that the phosphorylation of transfected N-terminal MYRF (pMYRF) was promoted by treatment with the PKG activator of 8-Br-cGMP (10 or 100 μM) for 1 hr or co-transfected 150Q-HTT for 24 hr, which was blocked by treatment of the PKG inhibitors of RKRARKE (50 μM) or KT5823 (5 μM) for 12 hr. trans-nMYRF: transfected N-terminal MYRF.",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "Western blotting of N2a cell line that was transfected with AAV-PRKG2 for 48 hr. The blots were probed with anti-Ser259 (pMYRF) antibody. Note that overexpression of PRKG2 increased phosphorylation of N-terminal MYRF (nMYRF) in a dose-dependent manner.",
    "ncbi_link": "PRKG2: 19092"
  },
  {
    "caption": "Stereotaxic injection of AAV-GFP virus into the corpus callosum (CC, indicated between two dotted lines) in the mouse brain. Ctx: cortex, Str: striatum. Scale bar: 100 μm..   Immunohistochemical staining with anti-Ser259 (pMYRF) showing that AAV-PRKG2, but not AAV-GFP, promotes MYRF phosphorylation in the corpus callosum. Scale bar: 40 μm.   ",
    "ncbi_link": "GFP: 
PRKG2: 19092"
  },
  {
    "caption": "Double immunofluorescent staining with antibodies to PRKG2 and Ser259 showing that AAV-PRKG2, but not AAV-GFP (green), promotes MYRF phosphorylation (red) in the injected corpus callosum. Scale bar: 40 μm.",
    "ncbi_link": "GFP: 
PRKG2: 19092"
  },
  {
    "caption": "Western blotting analysis of the mouse corpus callosum tissues using anti-Ser259 (pMYRF), phosphor-PRKG2 (pPRKG2) or phosphor-VASP (pVASP). Note that overexpression of mouse PRKG2 leads to the phosphorylation of MYRF and VASP. fMYRF: full-length MYRF, nMYRF: N-terminal MYRF.",
    "ncbi_link": "PRKG2: 19092"
  },
  {
    "caption": "Construction of AAV-U6-gRNA-CMV-RFP vector expressing PRKG2 gRNA under the U6 promoter and RFP protein under the CMV promoter, respectively. AAV-gRNA-PRKG2 was injected into the corpus callosum (CC, indicated between two dotted lines) in PLP-150Q/Cas9 mouse at 2 months of age and the injected tissues were isolated 4 weeks after injection (lower panel). Ctx: cortex, Str: striatum, LV: lateral ventricle. Scale bar: 100 μm",
    "ncbi_link": "Cas9: 
RFP: 
PLP: 18823
PRKG2: 19092"
  },
  {
    "caption": "Western blotting analysis of the PLP-150Q/Cas9 mouse corpus callosum tissues using the antibody to Ser259 (pMYRF), phosphor-PRKG2 or MBP. Note that reduction of mouse PRKG2 by CRISPR/Cas9 leads to the decreased MYRF phosphorylation and the increased expression of MBP. The ratios of pMYRF to MYRF or MBP to GAPDH obtained from 3 independent experiments were presented under the blots. Student's t-test; pMYRF: ***P=0.00026; MBP; **P=0.0036. Data are presented as mean ±SEM. fMYRF: full-length MYRF, nMYRF: N-terminal MYRF.",
    "ncbi_link": "Cas9: 
CRISPR: 
PLP: 18823
PRKG2: 19092"
  },
  {
    "caption": "Immunohistochemical staining with antibody to Ser259 showed that knocking down PRKG2 reduced MYRF phosphorylation in the corpus callosum of PLP-150Q mouse. Scale bar: 40 μm.",
    "ncbi_link": "PLP: 18823
PRKG2: 19092"
  },
  {
    "caption": "Immunofluorescent staining with antibodies to Ser259 or MBP showed the AAV- PRKG2-gRNA (red) injection increased MBP expression (green) as compared with AAV-gRNA-control. Scale bar: 40 μm.",
    "ncbi_link": "PRKG2: 19092"
  },
  {
    "caption": "Quantitative analysis of the MBP-positive cells in the corpus callosum injected with control-gRNA or PRKG2-gRNA. Twenty random fields (40X) in each section were examined. n=3 mice in each group. One-way ANNOVA with Tukey's test; ***P=4.43x10-5. Data are mean ±SEM.",
    "ncbi_link": "PRKG2: 19092"
  },
  {
    "caption": "A Representative images of Notch activation labeled by Tg(Tp1:mVenus)(green) and mature MGs stained with glutamate synthase (GS, magenta) at 4 dpf in Notch ligands (dla-/-/dlb-/-/dlc-/-/dld-/-/jag1b-/-/jag2b-/-) mutants.",
    "ncbi_link": "dla: 30131
dlb: 30141
dlc: 30120
dld: 30138
jag1b: 140423
jag2b: 140422"
  },
  {
    "caption": "B, C Quantitative plots showing the numbers of Notch activation (Tp1+) cells (B) and mature MG (GS+) cells (C) in A at 4 dpf. In total, we collected 11 fish for wild-type fish; 8 fish for jag2b-/- mutants; 15 fish for dla-/- mutants; 19 fish for dld-/- mutants; 19 fish for dlc-/- mutants, 11 fish for dlb-/- mutants, 11 fish for jag1b-/- mutants (mean ± SEM; ***p<0.001, t-test).",
    "ncbi_link": "dla: 30131
dlb: 30141
dlc: 30120
dld: 30138
jag1b: 140423
jag2b: 140422"
  },
  {
    "caption": "A Upper: representative images showing that GS+ MGs (magenta) were rarely observed in 5-dpf jag2b-/- mutants expressing H2B-CFP (green) driven by the crx promoter. Bottom: representative images showing that GS+ MGs (magenta) were frequently rescued underneath PRs when jag2b expression (green) was driven by the crx promoter in 5-dpf jag2b-/- mutants. The area of retina is labeled with solid line, and each layer structure is labeled with dashed lines and marked with outer nuclear layer (ONL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Scale bars: 20μm. The remaining MGs are indicated by white arrowheads, and the rescued MGs are indicated by yellow arrows. B Quantification of GS+ MGs (magenta in A) with (green) or without (gray) CFP expression driven by the crx promoter. Ctrl indicates H2B-CFP expression driven by the crx promoter (n = 16 larvae); rescue indicates jag2b-H2B-CFP expression driven by the crx promoter (n = 21 larvae, mean ± SEM; * p<0.05, ns, no significant difference, pair-wised t-test). C The proportions of jag2b-misexpressing PRs (Green) with underneath MGs (GS+, magenta in A) in 5-dpf jag2b-/- mutants and all MGs in retina. In total, we analyzed retinae of 16 control (Ctrl, jag2b-/- , crx::h2b-ecfp expression) and 21 rescue (jag2b-/-, crx::jag2b expression) larvae (Mean ± SEM; ***p<0.001, t-test).",
    "ncbi_link": "ecfp: 
h2b: 
crx: 81881
jag2b: 140422"
  },
  {
    "caption": "D Representative image showing the GS+, but vsx1- expression in the progeny of Tp1+ Müller-like differentiating MGs at wild-type (jag2b+/+). Layer structure indicated in (A). E The percentage of the progeny of Müller-like Tp1+ differentiating MG precursors (red+) expression GS (gray), vsx1 (green), or both negative (magenta) in wild-type (jag2b+/+) fish (n = 14, Mean ± SEM; ***p<0.001, t-test). F Representative image showing vsx1+, but GS- expression in the progeny of Tp1+ Müller-like differentiating MGs in jag2b-/- mutants. Layer structure indicated in (A). G The percentage of the progeny of Müller-like Tp1+ differentiating MG precursors (red+) expressing GS (gray), vsx1 (green), or both negative (magenta) in jag2b-/- mutants (n = 29, mean ± SEM; ***p<0.001, t-test).",
    "ncbi_link": "jag2b: 140422"
  },
  {
    "caption": "A Representative images of Notch activation labeled by Tg(Tp1:mVenus)( green) and mature MGs stained with glutamate synthase (GS, magenta) at 4 dpf in Notch receptors (notch1a-/-/notch1b-/-/notch3-/-) mutants. Scale Bars: 20 μm. B Quantitative plots showing the numbers of cells with active Notch (Tp1+) and mature MG (GS+) cells at 4 dpf. In total, we collected 4 fish for wild-type fish; 7 fish for notch1a-/- mutants; 5 fish for notch1b-/- mutants; 18 fish for notch3-/- mutants (Mean ± SEM; ** p<0.01; ***p<0.001, t-test).",
    "ncbi_link": "notch1a: 30718
notch1b: 794892
notch3: 58066"
  },
  {
    "caption": "C Representative images showing that GS+ MGs (magenta) were rarely observed when H2B-CFP expression (green) was driven by the gfap promoter in 5-dpf jag2b-/- mutants. The area between the upper dashed and solid lines is the outer nuclear layer (ONL). The area in the middle two dash lines is the inner plexiform layer (IPL). INL, inner nuclear layer; GCL, ganglion cell layer. D Representative images showing that GS+ MGs (magenta) were frequently rescued underneath cells with notch3 expression (green) driven by the gfap promoter in 5-dpf jag2b-/- mutants. Layer structure is similar as (C). E The cell number of GS+ MGs (magenta) with or without CFP expression driven by gfap promoter. Ctrl: H2B-CFP expression (green) driven by the gfap promoter (n = 5 fish); rescue: notch1b (n = 13 fish) and notch3 (n = 17 fish) NICD-H2B-CFP expression (green) driven by the gfap promoter (Mean ± SEM; * p<0.05, ***p<0.001, ns, no significant difference, pair-wised t-test). F The proportions of notch1b and notch3 NICD-misexpressing cells (green) with underneath MGs (GS+, magenta) in 5-dpf jag2b-/- mutants, indicating that gfap promoter-driven notch1b (n = 13 fish) or notch3 (n = 17 fish) NICD expression could rescue MG loss in jag2b-/- mutants (Mean ± SEM; ***p<0.001, t-test).",
    "ncbi_link": "CFP: 
H2B: 
gfap: 30646
jag2b: 140422
notch1b: 794892
notch3: 58066"
  },
  {
    "caption": "RIGER analysis to identify genes that are preferentially essential in FUS-DDIT3-expressing SCP-1 cells. EV-transduced SCP-1 cells and 20 FUS-DDIT3-negative cancer cell lines screened with the same shRNA library were used as reference set. Genes were ranked according to relative shRNA depletion, and YAP1 was identified as top FUS‑DDIT3‑specific essential gene. NES, normalized enrichment score.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521
YAP1: 10413"
  },
  {
    "caption": "Competition assays with SCP-1 cells transduced with RFP-labeled NTC or YAP1 shRNAs. Flow cytometric quantification of RFP-positive cells on day 9 relative to day 3 showed that YAP1 knockdown was preferentially toxic to FUS-DDIT3‑expressing cultures.",
    "ncbi_link": "RFP: 
DDIT3: 1649
FUS: 2521
YAP1: 10413"
  },
  {
    "caption": "Expression of YAP1 in SCP‑1 cells transduced with FUS‑DDIT3 or EV and liposarcoma cell lines. One of at least two independent experiments with similar results is shown. FUS‑DDIT3‑expressing cell types are indicated in red.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521"
  },
  {
    "caption": "Expression of YAP1 in cytoplasmic (yellow) and nuclear (blue) fractions from SCP-1 cells transduced with FUS-DDIT3 or EV and liposarcoma cell lines. One of at least two independent experiments with similar results is shown. FUS‑DDIT3‑expressing cell types are indicated in red.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521"
  },
  {
    "caption": "Competition assays with liposarcoma cell lines transduced with RFP-labeled NTC or YAP1 shRNAs. Flow cytometric quantification of RFP-positive cells on day 17 relative to day 3 showed that YAP1 knockdown was preferentially toxic to MLS cells. Error bars represent the mean ± SD of two independent experiments.",
    "ncbi_link": "RFP: 
YAP1: 10413"
  },
  {
    "caption": "Competition assays with MLS 1765-92 cells transduced with an RFP‑labeled NTC shRNA or an RFP-labeled shRNA against the YAP1 3' UTR following transduction with EV or the YAP1 coding sequence. Flow cytometric quantification of RFP‑positive cells on day 17 relative to day 3 showed that cell viability was rescued by expression of the shRNA‑resistant YAP1 cDNA. Error bars represent the mean ± SD of two independent experiments.",
    "ncbi_link": "RFP: 
YAP1: 10413"
  },
  {
    "caption": "Cell viability and expression of FOXM1 and PLK1 in MLS cell lines following siRNA-mediated YAP1 knockdown. Error bars represent the mean ± SD of three independent experiments, unpaired t-test. The blots represent one of at least three independent experiments with similar results.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Flow cytometric cell cycle analysis of MLS cell lines following shRNA‑mediated YAP1 knockdown. Error bars represent the mean ± SD of three independent experiments, two-way ANOVA; ns, not significant.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Senescence‑associated β‑galactosidase (SABG) staining intensity in MLS cell lines following shRNA-mediated YAP1 knockdown. Error bars represent the mean ± SD of ten random microscopic fields, two-way ANOVA).",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Expression of CDKN1A, CDKN2A, total and phosphorylated RB1, and TP53 in MLS cell lines following shRNA‑mediated YAP1 knockdown. One of at least two independent experiments with similar results is shown.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Expression of cleaved PARP and cleaved caspase 3/8 in MLS cell lines following shRNA-mediated YAP1 knockdown. One of at least two independent experiments with similar results is shown.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Expression of YAP1 and downstream effectors in SCP-1 cells transduced with FUS‑DDIT3 or EV. One of at least three independent experiments with similar results is shown.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521"
  },
  {
    "caption": "Expression of YAP1 and downstream effectors in cytoplasmic (yellow) and nuclear (blue) fractions from SCP-1 cells transduced with FUS‑DDIT3 or EV. One of at least two independent experiments with similar results is shown.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521"
  },
  {
    "caption": "YAP1-responsive luciferase activity in SCP-1 cells transduced with FUS‑DDIT3. Relative luciferase activity is displayed as fold change relative to control. Error bars represent the mean ± SD of three independent experiments, unpaired t-test.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521"
  },
  {
    "caption": "Co‑IP of transiently expressed FUS‑DDIT3 and YAP1 from HEK293T cells. V5-tagged YAP1 was pulled down using an anti-V5 antibody, and interacting proteins were detected by immunoblotting. One of at least two independent experiments with similar results is shown.",
    "ncbi_link": "DDIT3: 1649
FUS: 2521
YAP1: 10413"
  },
  {
    "caption": "YAP1-responsive luciferase activity in MLS cell lines transfected with a constitutively active YAP1S127A mutant and treated with 1 µM verteporfin. Relative luciferase activity is displayed relative to control. Error bars represent the mean ± SD of three independent experiments, unpaired t-test.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Tumor formation on chicken CAM of MLS cell lines following shRNA-mediated YAP1 knockdown. The number of tumors is given above each bar, Fisher exact test; ns, not significant.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "Ex vivo generation of CAR T cells. Activated human PBMC were left untransduced or incubated with CD8-LVCD19CAR at an MOI of 2. Five days later, expression of CD19-CAR and CD8 were determined on CD3+ cells. Numbers indicate the percentage of cells in the respective gate.",
    "ncbi_link": "CD19CAR: 
CD8: 925"
  },
  {
    "caption": "Mice were transplanted with B-cell depleted human PBMC and then received CD8-LVCD19CAR (filled circle) or PBS (open circle). As control, CD8-LVCD19CAR or PBS were injected into mice transplanted with non-depleted PBMC. Data represent mean ± SD for all groups (CD8-LVCD19CAR: n=6 in D, n=4 in G; CD8-LVRFP: n=4; PBS: n=4 in G, all others n=3).",
    "ncbi_link": "CD19CAR: 
RFP: 
CD8: 925"
  },
  {
    "caption": "CAR T cell levels in the CD8+ and CD8- T cells harvested from blood, spleen and bone marrow of PBS (PBS) or vector-injected (CAR) mice determined by flow cytometry.",
    "ncbi_link": "CAR: "
  },
  {
    "caption": "Immunohistochemistry of paraffin embedded sections from the lungs, brain meninges, brain striatum, spleen and liver of the vector-injected mouse M16 (CAR) and a control mouse injected with PBS (PBS) stained against CD8 (αCD8), the CAR (αCAR), CD4 (αCD4), or CD19 (αCD19). Black arrowheads point at infiltrated lymphocytes, red arrowheads at histiocytes, and the yellow line indicates B-lymphocyte rich zones.",
    "ncbi_link": "CAR: "
  },
  {
    "caption": "(K). The mRNA expression of CD137, CD40, TBX1, TMEM26, CITED1 and slc27a1 in iWAT of male mice supplemented with AKG for 11 weeks (n = 8 per group).",
    "ncbi_link": "CD40: 21939
CITED1: 12705
slc27a1: 26457
TBX1: 21380
TMEM26: 327766
CD137: 21942"
  },
  {
    "caption": "(R). The mRNA expression of PPARγ, FASN and ACC in the gWAT and iWAT from male mice supplemented with AKG for 11 weeks (n = 6 per group).",
    "ncbi_link": "ACC: 100705///107476
FASN: 14104
PPARγ: 19016"
  },
  {
    "caption": "(B). The mRNA expression of OXGR1 in different tissues of 12-weeks male C57BL/6 mice (n = 3 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(D). The mRNA expression of OXGR1 in the adrenal gland of male mice 3 hrs after i.p. injection of saline or 10 mg/kg AKG, or immediately after 40-mins resistance exercise (n=8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(E). Immunoblots and quantification of OXGR1 protein expression in adrenal chromaffin cells treated with negative control (NC) siRNA or siOXGR1 (n = 3 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(F). E level in the medium from adrenal chromaffin cell cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 for 30 mins (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(G). Intracellular calcium ion [Ca2+] changes in adrenal medulla cell cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 (n = 30 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(H-I). Body weight gain (H) and cumulative food intake (I) of male WT control (littermates) or OXGR1 global knock out (OXGR1KO) mice. At 12 weeks of age, both control and KO mice were switched to HFD and further divided into two groups, receiving tap water or water supplemented with 2% AKG for 13 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(J-K). Representative images of body composition (J) and fat and lean mass index (K) of male WT or OXGR1KO mice treated with AKG for 13 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(L-M). Weight index of iWAT (L) and gWAT (M) in male WT or OXGR1KO mice treated with AKG for 13 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "(N-O). Immunoblots (N) and quantification (O) of p-HSL and ATGL protein in gWAT of male WT or OXGR1KO mice treated with AKG for 13 weeks (n = 4 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Oxygen consumption (P-Q) of male WT or OXGR1KO mice treated with AKG for 13 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "RER (R-S) of male WT or OXGR1KO mice treated with AKG for 13 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Body weight gain and cumulative food intake of male OXGR1 adrenal-specific reexpression mice (OXGR1REAG). Male OXGR1KO mice (8 weeks) were adrenal-specifically injected with control HBAAV2/9-GFP (OXGR1KO control) or HBAAV2/9-OXGR1 (OXGR1REAG). Two weeks after injections, mice were switched to HFD and further divided into two groups, receiving tap water or water supplemented with 2% AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "GFP: 
OXGR1: 239283"
  },
  {
    "caption": "Representative image of body composition and fat and lean mass index of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Weight index of gWAT and iWAT in male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Immunoblots and quantification of p-HSL and ATGL protein in gWAT of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Oxygen consumption of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "RER of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Body weight gain in male WT littermates and OXGR1KO mice. At 8 weeks of age, male C57BL/6 WT control or OXGR1KO mice were switched to HFD. After 12 weeks of HFD feeding, mice were further divided into two groups, receiving non-exercise or resistance exercise for 14 days. (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Exercise-induced body weight loss in male WT littermates and OXGR1KO mice. Body weights from exercise mice were subtracted by the average body weight of non-exercise control group for each genotype (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Exercise-induced fat mass loss in male WT littermates and OXGR1KO mice. Fat mass from exercise mice were subtracted by the average fat mass of non-exercise control group for each genotype (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Cumulative food intake of male WT littermates and OXGR1KO mice after 14-day resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Weight index of gWAT (E) and iWAT (F) of male OXGR1KO mice after 14-days resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Body composition of male OXGR1KO mice after 14-days resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Serum AKG levels of male WT and OXGR1KO mice after resistance exercise. Male WT and OXGR1KO mice (10 weeks) fed with normal chow were receiving resistance exercise for 40 min (n = 8 per group). The serum AKG levels were tested before and immediately after exercise.",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Serum E level in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "The mRNA expression in the BAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "protein expression of UCP1 in the BAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "the mRNA expression of HSL and ATGL n the gWAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group).",
    "ncbi_link": "HSL: 16890
OXGR1: 239283
ATGL: 66853"
  },
  {
    "caption": "Oxygen consumption in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "RER in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "Immunoblots and quantification of p-IKK/IKK, p65, p-IκB/IκB and OXGR1 protein in adrenal chromaffin cells cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 for 3 hrs (n = 3 per group).",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "p65 translocation in adrenal chromaffin cells cultured with vehicle + NC, vehicle + siOXGR1, AKG (100 μM) + NC or AKG + siOXGR1 for 3 hrs (n = 3 per group). Scale bars, 100 μm.",
    "ncbi_link": "OXGR1: 239283"
  },
  {
    "caption": "C-D) Immunoblots and quantification of lysates from Cos-1 cells transfected with plasmid pCI-mDGKk-HA or non-transfected (NT) and pre-transfected 24h before with siRNA control (siC) or against FMRP (siFMR1). GAPDH was used as a loading control. For quantification, the DGKk and FMRP signals were normalized against GAPDH signal and presented relative to the signal for siC treated cells (C). Immunoblots and quantification of lysates from Cos-1 cells transfected with pCI (empty plasmid), pCI-HA-∆N-DGKk, or pCI-mDGKk-HA, and pre-treated with siRNA control (siC) or against FMRP (siFMR1) (D). Quantifications as in C.",
    "ncbi_link": "HA: 
DGKk: 331374
FMR1: 2332"
  },
  {
    "caption": "A) HeLa cells transfected with indicated plasmids expressing mouse (m) or human (h) DGKk were analyzed by immunofluorescence confocal microscopy for HA tag (red) and Dapi staining (blue). ∆C1-hDGKk construct bears deletion of phorbol ester C1 domain (328-449).",
    "ncbi_link": "DGKk: 139189"
  },
  {
    "caption": "B) Immunoblots and quantification of lysates from Cos-1 cells transfected with plasmid pCI-HA-∆N-DGKk, untransfected (NT), or plasmid pCI control, with the indicated amount of plasmid (µg) and after 24h, incubated with puromycin (20µg/ml, 30 min) to measure rates of protein synthesis. GAPDH was used as a loading control. 0 indicates no puromycin treatment, -/+ indicates treatment without or with DGK inhibitor (DGKi) 3 µM R59022 and 0.2 µM R59949 at 6 µM, 15 min. Densitogram of puromycin incorporation is presented as change relative to mock transfected conditions.",
    "ncbi_link": "HA: 
DGKk: 331374"
  },
  {
    "caption": "C) Representative immunofluorescence staining of cortical neuron cultures transduced at 8 DIV (days in vitro) with 10e9 VG/ml of AAVRh10-GFP or AAVRh10-∆N-DGKk and assessed after 5 days using anti-MAP2 and anti-HA for ∆N-DGKk or direct 488 nm excitation for GFP. DAPI was used to visualize nuclei on merged images.",
    "ncbi_link": "GFP: 
DGKk: 331374"
  },
  {
    "caption": "D) Representative immunoblots of lysates from WT and Fmr1-KO cortical neurons transduced with AAVRh10-∆N-DGKk (AAV ∆N-DGKk), at the indicated titers (VG/ml culture volume) and quantification of phosphorylation and total levels of eIF4E. GAPDH was used as a loading control. For quantification, the phospho-protein signal was normalized first against total protein signal and is presented relative to the signal for WT culture.",
    "ncbi_link": "DGKk: 331374
Fmr1: 14265"
  },
  {
    "caption": "B) Viral titers (viral genome copy VG per cell) determined by qPCR in cortical, hippocampal and rest of brain areas of Fmr1-KO mice treated with saline solution (Vehicle), AAVPHP.eB-∆N-DGKk (PHP.eB), AAVRh10-∆N-DGKk (Rh10) 8 weeks after injections. Data are mean ± SEM. Each dot represents an individual mouse.",
    "ncbi_link": "DGKk: 331374
Fmr1: 14265"
  },
  {
    "caption": "C) Immunoblots and quantification of ∆N-DGKk protein in lysates from brain areas of mice treated as in B. GAPDH was used as a loading control. Densitogram of ∆N-DGKk expression is presented as change relative to vehicle conditions.",
    "ncbi_link": "DGKk: 331374"
  },
  {
    "caption": "D) Representative coronal brain sections processed for detection of ∆N-DGKk using immunohistochemistry on Fmr1-KO mice treated with indicated treatment, 8 weeks post-injections, counter stained with eosin hematoxylin. Adjacent sections were immunolabelled with NeuN. 3 mice per genotype were processed. The sections shown are between Bregma levels -1.50 mm and -1.80 mm. Scale bar is 2 mm. Magnifications of regions of cortex (c), hippocampus (h), and striatum (s) are shown in side panels, scale bar 200 µm.",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "E) Total phosphatidic acid (PA) level measure by mass spectrometry in cortex of WT mice treated with saline solution (WT-S) and Fmr1-KO mice treated with saline (Fmr1-S), AAVPHP.eB-∆N-DGKk (Fmr1-PHP.eB), AAVRh10-∆N-DGKk (Fmr1-Rh10) 8 weeks after injections. Data are expressed as mol % of total lipids and represented as median with interquartile range with minimum and maximum values. Statistics: one-way ANOVA and Tukey's multiple comparisons test, n=8 individual animals, except for WT-S and Fmr1-S n=11. **P < 0.01, ***P < 0.001.",
    "ncbi_link": "DGKk: 331374
Fmr1: 14265"
  },
  {
    "caption": "A. SHOXprotein representation and luciferase assay. The variants found in SHOX are indicated in red. Luciferase assays to test the impact of SHOX mutations on its transcriptional activity were performed on FGFR3 promoter in U2OS cells (n = 4). Experiments were performed in triplicates. pcDNA4-TO empty vector was used as control. R153L represents a mutation known to affect SHOXprotein activity and was used as positive control (Schneider et al., 2005). Homeodomain, DNA binding domain; Src Homology 3 domain; OAR, OtpAristalessRax domain. RLU, Relative Light Units.",
    "ncbi_link": "FGFR3: 2261
SHOX: 6473"
  },
  {
    "caption": "B. CYP26C1protein representation and luciferase assay. Variants found in CYP26C1 are indicated in green. Cignal-RARE system luciferase assays to test the impact of CYP26C1 variants on its RA degradation activity were performed in U2OS cells treated with 250 nM all-trans retinoic acid (ATRA) for 24 hours (n = 4). Experiments were performed in triplicates.pIRES2-EGFP empty vector was used as control. The residue C459 represents the Iron binding residue (Q6VOL0, UniProtKB) and was mutated to Ala and used as a positive control. TM, Transmembrane helix; P450, cytochrome p450 domain. RLU, Relative Light Units.",
    "ncbi_link": "CYP26C1: 340665"
  },
  {
    "caption": "A. Left panel, RT-PCR showing the expression of CYP26C1 mRNA in human primary chondrocytes. SOX9 was used as chondrocyte marker.",
    "ncbi_link": "CYP26C1: 340665
SOX9: 6662"
  },
  {
    "caption": "B. Relative expression of SHOX mRNA normalized to the reference genes SDHA and HPRT in human primary chondrocytes treated with ATRA 100 nM for 6h (n = 5). One outlier with high relative expression (2.3 fold) was excluded from ATRA 100 nM treatment (two-sided Grubb's test, Z value 2.34, p-value < 0.05).",
    "ncbi_link": "HPRT: 
SDHA: 
SHOX: 6473"
  },
  {
    "caption": "C. SHOX promoter was cloned in pGL3basic for luciferase reporter experiments as previously described (Verdin et al, 2015). In silico analysis of SHOX promoter identified three putative RXRa binding sites which were mutated to test their direct effect on SHOX expression upon treatment with ATRA 250 nM in U2OS cells (n = 4). Experiments were performed in triplicates. RLU, Relative Light Units.",
    "ncbi_link": "RXRa: 6256
SHOX: 6473"
  },
  {
    "caption": "A-C. Wild type embryos injected with control MO or with shox MO. (A) Lateral views of the embryos at 55 hours post fertilization (hpf). (B) Dorsal view and magnification on the lateral view of the embryos. Dotted line, pectoral fins. shox morphants show smaller fins compared to controls (n = 30 embryos).",
    "ncbi_link": "shox: 664748"
  },
  {
    "caption": "A-C. Wild type embryos injected with control MO or with shox MO. C. Expression of col2a1 at 55 hpf was examined by in situ hybridization in wild type embryos injected with control MO and with shox MO. Arrow and dotted line indicate the pectoral fin.",
    "ncbi_link": "col2a1: 562496
shox: 664748"
  },
  {
    "caption": "A-C. Wild type embryos injected with control MO or with shox MO. D. Pectoral fin area was measured by imageJ (n = 30 embryos).",
    "ncbi_link": "shox: 664748"
  },
  {
    "caption": "A-D. Wild type embryos injected with control MO or with cyp26c1 MO. (A) Lateral views of the embryos at 55 hours post fertilization (hpf). (B) Dorsal view and magnification on the lateral view of the embryos. Dotted line, pectoral fins; *, otic vesicle. cyp26c1 morphants show smaller fins compared to controls (n = 30 embryos).",
    "ncbi_link": "cyp26c1: 554036"
  },
  {
    "caption": "A-D. Wild type embryos injected with control MO or with cyp26c1 MO. (C, D) Expression of col2a1(C) and shox (D) at 55 hpf was examined by in situ hybridization in embryos injected with control MO or with cyp26c1 MO. (C) Dorsal view and magnification on the pectoral fins of col2a1expression. Arrow and dotted line indicate the pectoral fin. (D) Dorsal view and magnification on the pectoral fins of shox expression. Arrow and dotted line indicate the pectoral fin.",
    "ncbi_link": "col2a1: 562496
cyp26c1: 554036
shox: 664748"
  },
  {
    "caption": "F. Cignal-RARE system luciferase assay testing cyp26c1 MO on RA acid levels in zebrafishembryos (n = 5 replicates). Embryos were separated in groups of 20-30 and luciferase assayed. RLU, Relative Light Units.",
    "ncbi_link": "cyp26c1: 554036"
  },
  {
    "caption": "G. Relative shox mRNA expression normalized to reference genes eef1a and b-actin in zebrafishembryos injected with control MO or cyp26c1 MO (n = 4). RNA was extracted from 10-15 injected embryos at 55 hours post fertilization.",
    "ncbi_link": "b-actin: 
eef1a: 
cyp26c1: 554036
shox: 664748"
  },
  {
    "caption": "H. Relative shox mRNA expression normalized to reference genes eef1a and b-actin in zebrafishembryos treated with 100 nM ATRA (n = 4). Embryos were collected at 24 hpf and treated with mock control or ATRA. RNA was extracted from 10-15 embryos after 6 hours treatment.",
    "ncbi_link": "b-actin: 
eef1a: 
shox: 664748"
  },
  {
    "caption": "A-C. Wild type embryos injected with control MO, subphenotypic doses of shox MO, cyp26c1 MO or a combination of shox + cyp26c1 MOs. (A) Dorsal views of the embryos at 55 hours post fertilization (hpf). Dotted line, pectoral fins. shox + cyp26c1 double morphants show smaller fins compared to control and single MOs (n = 30 embryos).",
    "ncbi_link": "cyp26c1: 554036
shox: 664748"
  },
  {
    "caption": "A-C. Wild type embryos injected with control MO, subphenotypic doses of shox MO, cyp26c1 MO or a combination of shox + cyp26c1 MOs. (B, C) Dorsal view and magnification on the pectoral fins of col2a1expression at 55 hpf. Arrow and dotted line indicate the pectoral fin.",
    "ncbi_link": "col2a1: 562496
cyp26c1: 554036
shox: 664748"
  },
  {
    "caption": "E. Relative expression of shox mRNA normalized to reference genes eef1a and b-actin in zebrafishembryos injected with control MO, shox MO, cyp26c1 MO, or shox + cyp26c1 MOs (n = 4). RNA was extracted from 10-15 injected embryos at 55 hours post fertilization.",
    "ncbi_link": "b-actin: 
eef1a: 
cyp26c1: 554036
shox: 664748"
  },
  {
    "caption": "(B) A fragment encompassing amino acids 432-520 of Atg13 (wt) or the corresponding FV mutant (FV) was expressed in E. coli and incubated in excess with an immobilized GST‐tagged fragment of Atg1 (amino acids 501-897) purified from E. coli (GST‐Atg1). Input (5.5%) and bound proteins were analysed by coomassie blue staining, which stains proteins proportional to their size. The size of marker proteins (in kDa) is indicated on the left.",
    "ncbi_link": "Atg13: 856315"
  },
  {
    "caption": "(C) ATG1‐TAP atg13Δ cells containing endogenously GFP‐tagged Atg17, Atg29 or Vac8 and wild‐type (wt) or the Atg13 FV‐mutant (F468A; V469A) were grown to mid log phase. Atg1 was immunoprecipitated and its association with Atg13 and the GFP‐tagged proteins was analysed by immunoblotting. Extract inputs are shown in Supplementary Figure S1B.",
    "ncbi_link": "Atg13: 856315
atg13: 856315"
  },
  {
    "caption": "(D) atg1Δ and atg1Δatg13Δ cells expressing HA‐tagged Atg1 and wild‐type (wt) cells containing an empty plasmid were grown to mid log phase (rich), and then treated with rapamycin (rapa) or starved for 4 h in SD‐N medium (starv). Atg1 was immunoprecipitated and its association with Atg13 analysed by immunoblotting. Note that phosphorylated Atg13 isolated from cells grown in rich medium migrates slightly slower on SDS-PAGE, and the extent corresponds to the shift typically observed under our gel conditions.",
    "ncbi_link": "atg1: 852695
atg13: 856315"
  },
  {
    "caption": "(F) Histone3‐HA tagged Atg1 was expressed together with wild‐type (wt) or the Atg13‐FV mutant fused to Suv methylase (Suv) in atg1Δatg13Δ cells, or for control together with Pbs2‐Suv in atg1Δ cells. Logarithmically growing cultures were treated with rapamycin (rapa) for 0 or 120 min, and methylation was monitored by preparing cell extracts and western blotting with an anti‐trimethylation‐specific antibody. Note that Suv‐, GFP‐ or TAP‐tagged Atg13 are fully functional, however, do not show the characteristic phosphorylation‐induced reduced mobility observed with the untagged protein under our gel conditions.",
    "ncbi_link": "atg1: 852695
Atg13: 856315
atg13: 856315
Pbs2: 853313"
  },
  {
    "caption": "(G) atg1Δatg13Δ cells containing TAP‐tagged wild‐type Atg1 (wt) or the Atg1 kinase‐dead (kd) K54A mutant and wild‐type Atg13, the Atg13‐FV mutant or an empty plasmid were grown to mid log phase. Atg1 was immunoprecipitated and its autophosphorylation activity was measured by autoradiography in vitro.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
Atg13: 856315
atg13: 856315"
  },
  {
    "caption": "(H) pho8Δ60pho13Δatg13Δ cells expressing wild‐type Atg13 (wt), the Atg13‐FV mutant (FV) or an empty plasmid were grown to mid log phase and starved for 4 h in SD‐N medium. Pho8Δ60‐specific alkaline phosphatase (ALP) activity (nmol/min/mg) was measured in three independent experiments as described in 'Materials and methods', and plotted as relative ALP activity with standard deviation (s.d.) compared to the wild‐type controls.",
    "ncbi_link": "Atg13: 856315
atg13: 856315
pho13: 851362
pho8: 852092"
  },
  {
    "caption": "(I) atg13 cells expressing GFP‐Atg8 and containing wild‐type Atg13, the Atg13‐FV mutant or an empty plasmid were grown to mid log phase with and without starvation for 4 h in SD‐N. Processing of endogenous Ape1 and cleavage of GFP‐Atg8 was analysed by western blotting, and quantified by calculating the ratio of cleaved versus uncleaved Ape1 or GFP‐Atg8, respectively. The asterisk marks a non‐specific band detected by the Atg13 antibody. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "Atg13: 856315
atg13: 856315
Atg8: 852200"
  },
  {
    "caption": "(B) GST‐Atg8 or GST‐Ubiquitin (Ub) was purified from E. coli and bound to GSH beads. Wild‐type Atg1‐TAP or the VE and EYE mutants were purified from yeast, incubated with the immobilized GST proteins and bound proteins analysed by western blotting.",
    "ncbi_link": "Atg1: 852695"
  },
  {
    "caption": "(C) (C) GST‐Atg8 and GST‐Ubiquitin were immobilized as described in (B), and probed for their ability to bind Atg1‐TAP isolated from wild‐type or atg13Δ cells.",
    "ncbi_link": "atg13: 856315"
  },
  {
    "caption": "(D) atg1Δatg13Δ cells expressing as indicated wild‐type Atg1‐TAP or the VE or EYE mutants, and wild‐type Atg13 or the Atg13‐FV mutant were grown to mid log phase. Atg1 was immunoprecipitated and its association with Atg13 was determined by western blotting.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
Atg13: 856315
atg13: 856315"
  },
  {
    "caption": "(F) HEK293 cells were co‐transfected with GFP or GFP‐GABARAP along with either wild‐type HA‐ULK1 or the DFP mutant. GFP and GFP‐GABARAP were immobilized on GFP‐Trap resin and HA‐ULK1 binding was analysed by western blotting. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "GABARAP: 11337
ULK1: 8408"
  },
  {
    "caption": "(A) atg1Δatg13Δ cells containing an empty control plasmid, wild‐type or the indicated Atg1 mutants, and Atg13 wild‐type, the Atg13‐FVmutant or an empty plasmid were grown to mid log phase. Processing of endogenous Ape1 was analysed by western blotting, and quantified as described in the legend of Figure 1I. Expression of the different proteins was controlled by immunoblotting with antibodies against Atg1 or Atg13. The asterisk marks a non‐specific band detected by the Atg13 antibody.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
Atg13: 856315
atg13: 856315"
  },
  {
    "caption": "(B) pho8Δ60pho13Δatg1Δ cells expressing wild‐type (wt), kinase‐dead (kd), Atg1‐VE (VE) or ‐EYE (EYE) mutants or an empty plasmid were grown to mid log phase and starved for 4 h in SD‐N medium. Pho8Δ60‐specific alkaline phosphatase (ALP) activity (nmol/min/mg) was measured in three independent experiments as described in 'Materials and methods', and plotted as relative ALP activity with standard deviation (s.d.) compared to the wild‐type controls.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
pho13: 851362
pho8: 852092"
  },
  {
    "caption": "(C) Cells as in (A) expressing GFP‐Atg8 were grown to mid log phase with starvation for 4 h in SD‐N medium. The processing of GFP‐Atg8 was analysed and quantified as in Figure 1I.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(D) Exponentially growing atg1Δ and atg1Δatg8Δ strains expressing the PAS marker Ape1‐RFP and either GFP‐tagged wild‐type Atg1 or the Atg1‐VE mutant were examined by fluorescence microscopy. Bar=5 μm.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
atg8: 852200"
  },
  {
    "caption": "(E) atg1Δ cells containing TAP‐tagged wild‐type or the indicated Atg1‐mutants were grown to mid log phase. Atg1 was immunoprecipitated and its in vitro autophosphorylation activity was measured by autoradiography. The kinase‐dead (kd) Atg1‐mutant K54A serves as a negative control. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "Atg1: 852695"
  },
  {
    "caption": "(A) Exponentially growing ypt7Δ cells were starved in SD‐N medium for 4 h, lysed and the extract separated into a cytoplasmic (S) and a 5000 g membrane pellet fraction. The pellet was treated with (+) or without (−) TX‐100, centrifuged and the supernatant (S) and pellet (P) fractions analysed by western blotting with anti‐Atg1, anti‐Pep12 and anti‐Pgk1 antibodies.",
    "ncbi_link": "ypt7: 855012"
  },
  {
    "caption": "(B) Exponentially growing ypt7Δatg1Δ cells expressing wild‐type Atg1 or the Atg1‐VE mutant protein were starved in SD‐N for 4 h, lysed and the extract separated into cytoplasmic (S) and membrane (P) fractions. The fractions were analysed by western blotting with anti‐Atg1, anti‐Pgk1 and anti‐Ape1 antibodies, and the ratio of Atg1 to Ape1 in the pellet fractions was quantified and indicated as a ratio compared to wild‐type cells.",
    "ncbi_link": "Atg1: 852695
atg1: 852695
ypt7: 855012"
  },
  {
    "caption": "(C) HEK293 cells were co‐transfected with GFP‐GABARAP and HA‐ULK1, starved for 2 h, and subsequently immunostained for HA (red) and WIPI2 (white). The arrows mark putative autophagosomes that stain positive for all three markers. Bar=10 μm.",
    "ncbi_link": "GABARAP: 11337
ULK1: 8408"
  },
  {
    "caption": "(D) HEK293 cells stably expressing GFP‐LC3 were transfected with wild‐type HA‐ULK1 or the DFP mutant, and immunostained for HA and WIPI2 after 2 h starvation. HA‐ULK1 and WIPI2 spot numbers were counted using Imaris software in over 70 cells (from one out of two experiments) and plotted as the ratio of ULK1 to WIPI2 puncta. ***Indicates a statistically significant P‐value of 0.0001. One of the two independent experiments is shown.",
    "ncbi_link": "LC3: 440738///81631///84557
ULK1: 8408"
  },
  {
    "caption": "(E) Quantification of HA‐ULK1 and WIPI2 spot numbers in HEK293 cells expressing wild‐type HA‐ULK1 or the DFP mutant. Cells were treated as above, and the spot number counted using Imaris software. A representative immunofluorescence image is shown in Supplementary Figure S3F. *** and * indicate P‐values of 0.0001 or 0.0158, respectively. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(A) atg1Δ cells containing either wild‐type Atg1 or the kinase‐dead Atg1‐T226A mutant tagged with GFP were grown to mid log phase followed by starvation for 24 h in SD‐N. Samples were taken at indicated time points and GFP cleavage was analysed by western blotting. Processing of endogenous Ape1 under starvation conditions monitors the autophagic flux.",
    "ncbi_link": "Atg1: 852695
atg1: 852695"
  },
  {
    "caption": "(B) atg1Δ cells containing either GFP‐tagged wild‐type Atg1 or the Atg1‐VE mutant were grown and analysed as in (A).",
    "ncbi_link": "Atg1: 852695
atg1: 852695"
  },
  {
    "caption": "(C) atg1Δpep4Δ cells containing YFP‐tagged wild‐type Atg1 or the Atg1‐VE mutant were grown to log phase and starved in SD‐N. Cells were monitored by time‐lapse microscopy and the vacuolar accumulation of Atg1 was quantified as described in 'Materials and methods'. Data are plotted as the mean±s.e.m. from at least 90 quantified cells. Additional images are shown in Supplementary Figure S3H. Bar=5 μm.",
    "ncbi_link": "Atg1: 852695
pep4: 855949"
  },
  {
    "caption": "(D) atg1Δatg13Δ cells expressing GFP‐tagged wild‐type Atg13, and either wild‐type Atg1 or the Atg1‐VE mutant (left panel) and wild‐type cells containing Atg13‐GFP and either wild‐type Atg13 or Atg13‐FV were grown to mid log phase followed by starvation for 6 h in SD‐N media. GFP cleavage was analysed by western blotting. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "Atg1: 852695
Atg13: 856315"
  },
  {
    "caption": "E. Total RNAs from naïve CD4+ T cells, PHA-stimulated CD4+ T cells and resting memory CD4+ T cells were extracted and proceeded to RT-qPCR to quantitate the relative expression of CBX4. The expression of CBX4 in PHA-stimulated and resting memory CD4+ T cells was normalized to naïve CD4+ T cells. Data information: Data represented mean ± SEM in biological triplicate. p-Values were calculated by one-way ANOVA with Tukey's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "CBX4: 8535"
  },
  {
    "caption": "G. HA-tagged EZH2 was co-overexpressed with Flag-tagged SUMO1, Flag-tagged UBC9 or Flag-tagged CBX4, and siNC. In the last group, HA-tagged EZH2 was co-overexpressed with Flag-tagged SUMO1, Flag-tagged UBC9 and siCBX4. EZH2 was IP with anti-HA beads. Both total and IP samples were IB with antibodies against HA, Flag and GAPDH. The expression ratios of SUMO1-EZH2 within each group were showed below the figure. H. HA-tagged EZH2 was co-overexpressed with Flag-tagged SUMO4, Flag-tagged UBC9 or Flag-tagged CBX4, and siNC. In the last group, HA-tagged EZH2 was co-overexpressed with Flag-tagged SUMO4, Flag-tagged UBC9 and siCBX4. EZH2 was IP with anti-HA beads. Both total and IP samples were IB with antibodies against HA, Flag and GAPDH. The expression ratios of SUMO4-EZH2 within each group were showed below the figure.",
    "ncbi_link": "Flag: 
HA: 
CBX4: 8535
EZH2: 2146
SUMO1: 7341
SUMO4: 387082
UBC9: 7329"
  },
  {
    "caption": "B. Two micrograms (2 μg) of HA-tagged EZH2 were co-overexpressed with 4 μg of Flag-tagged SUMO4, 250 ng of Flag-tagged UBC9, 250 ng of Flag-tagged CBX4 or CBX4mut within 6 cm dishes. The CBX4mut was the LLPS-deficient CBX4. EZH2 was IP with anti-HA beads. Both total and IP samples were IB with antibodies against HA, Flag and GAPDH. The expression ratios of SUMO4-EZH2 were marked below the panel.",
    "ncbi_link": "Flag: 
HA: 
CBX4: 8535
EZH2: 2146
SUMO4: 387082
UBC9: 7329"
  },
  {
    "caption": "D. The endogenous EZH2 in TZM-bl cells within 6 cm dishes was knocked down by siRNAs targeting 3'UTR of EZH2 mRNA, followed by the overexpression of 2 μg of EZH2, 4 μg of Flag-tagged SUMO4, 250 ng of Flag-tagged UBC9 or 250 ng of Flag-tagged CBX4. EZH2 was IP with anti-EZH2 antibodies. IP samples were IB with anti-EZH2 antibodies. Total samples were IB with anti-EZH2, anti-H3K27me3, anti-Histone H3 and anti-GAPDH antibodies. The expression ratios of SUMO4-EZH2 and H3K27me3 were marked below the panel.",
    "ncbi_link": "Flag: 
CBX4: 8535
EZH2: 2146
SUMO4: 387082
UBC9: 7329"
  },
  {
    "caption": "E. In the first group, HEK293T cells within 6 cm dishes were transfected with empty vectors. In the second group, 3 μg of EZH2 was overexpressed. In the third group, 3 μg of EZH2 was co-overexpressed with 2 μg of EED and 2 μg of SUZ12. In the fourth and sixth group, 3 μg of EZH2 was co-overexpressed with 2 μg of EED, 2 μg of SUZ12, 2 μg of SUMO4, 500 ng of UBC9 and 2 μg of CBX4. In the fifth group, 3 μg of EZH2mut (Y731D) was co-overexpressed with 2 μg of EED, 2 μg of SUZ12, 2 μg of SUMO4, 500 ng of UBC9 and 2 μg of CBX4. Forty-eight hours post transfection, EZH2 and EZH2mut were IP with anti-EZH2, followed by the incubation with 2 μg of mononucleosomes (H3.1) and 20 μM of the cofactor S-adenosyl-L-methionine (SAM) to measure the methyltransferase activity of EZH2. The IP reaction in the sixth group was incubated with 2 μg of mononucleosomes (H3.1 K27M) and 20 μM of SAM. Both total and IP samples were IB with anti-EZH2, GAPDH, H3K27me3 and H3.1 antibodies. The purities of recombinant mononucleosomes which included H3.1, H2B, H2A and H4 were verified by Coomassie blue staining. The expression ratios of SUMO4-EZH2 and H3K27me3 were marked below the panel.",
    "ncbi_link": "CBX4: 8535
EED: 8726
EZH2: 2146
SUMO4: 387082
SUZ12: 23512
UBC9: 7329"
  },
  {
    "caption": "A. PHA-activated primary CD4+ T cells were infected with wildtype HIV-1 viruses which harbored a GFP ORF after Nef gene, followed by infecting with shluc and shCBX4 lentiviruses respectively. The percentages of GFP-positive cells, which were HIV-1-expressing cells, were monitored every three days. Data information: Data represented mean ± SEM in biological triplicate. p-Values were calculated by two-way ANOVA with Sidak's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "GFP: 
luc: 
CBX4: 8535
Nef: 156110"
  },
  {
    "caption": "B, C. Primary CD4+ T cells were treated as in (A). On Day 6 post infection with HIV-1 viruses and shRNA lentiviruses, ChIP assays with antibodies against H3K27me3 and H2AK119Ub were conducted in both shluc and shCBX4 groups. Data information: Data represented mean ± SEM in biological triplicate. p-Values were calculated by two-way ANOVA with Sidak's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "luc: 
CBX4: 8535"
  },
  {
    "caption": "D. PHA-activated CD4+ T cells were infected with wildtype HIV-1 viruses as in (A). One group of HIV-1-infected CD4+ T cells were left untreated. One group of HIV-1-infected cells were infected with shluc. Another group of HIV-1-infected cells were infected with shCBX4. Two weeks later, one part of HIV-1-infected CD4+ T cells were reactivated by αCD3/αCD28/IL-2. One part of shluc- and shCBX4-infected cells were co-stimulated with LRA JQ-1. GFP-positive cells in each group were measured by flow cytometry to indicate reactivated HIV-1-infected cells. Data information: Data represented mean ± SEM in biological triplicate. p-Values were calculated by one-way ANOVA with Tukey's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "luc: 
CBX4: 8535"
  },
  {
    "caption": "E-G. Primary CD4+ T cells, which contained latent HIV-1-infected cells, were isolated from three HIV-1-infected individuals. One group of cells were untreated. One group of cells were activated with αCD3/αCD28/IL-2. Another two groups of cells were transfected with siNC and siCBX4 utilizing 4D-Nucleofector System respectively. Three days post transfection, the amounts of intracellular HIV-1 RNAs within each group were quantitated by RT-qPCR and represented as 103 copies per million CD4+ T cells. Data information: Data represented mean ± SEM in biological triplicate. p-Values were calculated by one-way ANOVA with Tukey's multiple comparisons test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "CBX4: 8535"
  },
  {
    "caption": "(b) Western blot analysis of HeLa cells treated with a second independent siRNA targeting ATG5, ATG7 or NDP52. GAPDH and total protein stained with Coomassie blue serve as loading controls.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
NDP52: 10241"
  },
  {
    "caption": "(i) Western blot analysis of DICER (monoclonal antibody 13D6) or control (EEF1A1) in HeLa cells treated with control siRNA or siRNA targeting DICER.",
    "ncbi_link": "DICER: 23405"
  },
  {
    "caption": "(k,l) RT-qPCR analysis of AGO1, AGO2 and DICER mRNA in HeLa cells treated for 12 h with DMSO, BAF or CQ (k) or siRNA for 84 h (l). Error bars show s.e.m. Uncropped images of blots are shown in Supplementary Fig. S3.",
    "ncbi_link": "AGO1: 26523
AGO2: 27161
DICER: 23405"
  },
  {
    "caption": "(b) Western blot of GEMIN4 or loading control (TUBA) in HeLa cells treated with control siRNA or siRNA targeting ATG5, ATG6 or ATG7.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
ATG6: 8678"
  },
  {
    "caption": "(g) Western blot analysis of GEMIN4, compared with loading controls (DCP1A, CLN3) in HeLa cells treated with control siRNA or siRNA targeting GEMIN3 and GEMIN4.",
    "ncbi_link": "GEMIN3: 11218
GEMIN4: 50628"
  },
  {
    "caption": "(h) Western blot analysis of HeLa cells treated with indicated combinations of control siRNA or siRNA targeting GEMIN3, GEMIN4 and ATG5. Western blot analysis of CLN3 and DCP1A are used to demonstrate equal loading of wells.",
    "ncbi_link": "ATG5: 9474
GEMIN3: 11218
GEMIN4: 50628"
  },
  {
    "caption": "(i) Western blot analysis with anti-UB monoclonal antibody (mono- and polyubiquitylated proteins, FK2 clone) in Flag immunoprecipitates performed under stringent denaturing conditions. Flag-AGO2 was induced for 24 h with tetracycline in HEK293T cells with Tet-inducible Flag-AGO2 stably integrated that had been treated 24 h before with the indicated siRNAs.",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "(j) Western blot analysis of HeLa cells treated with control siRNA or siRNA targeting ATG5 for 24 h. TUBA, α-tubulin loading control.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(k) Top, RT-qPCR analysis of miR-16 or let-7a levels in AGO2 immunoprecipitates from DMSO- and BAF-treated HeLa cells. Error bars represent s.e.m. Bottom, a representative western blot of AGO2 immunoprecipitates used in one replicate of these experiments. Uncropped images of blots are shown in Supplementary Fig. S3.",
    "ncbi_link": "AGO2: 27161
miR-16: 406951///406950
let-7a: 406883///406882///406881"
  },
  {
    "caption": "(a) Northern blot of miR-16 and let-7a in HeLa cells treated with siRNA for 84 h. Levels of U6, ethidium-bromide-stained total RNA on northern membrane (loading) and 28S and 18S ribosomal RNA on 1% agarose gel are shown as controls for equal loading.",
    "ncbi_link": "18S: 
28S: 
U6: 
miR-16: 406951///406950
let-7a: 406883///406882///406881"
  },
  {
    "caption": "(b-d) RT-qPCR analysis of let-7a and miR-16 (b), pre-let-7a and pre-miR-16 (c) and let-7a* and miR-16* (d) in HeLa cells depleted of NDP52 or ATG5 with siRNA (84 h). n = 3 independent experiments; error bars represent s.e.m.",
    "ncbi_link": "ATG5: 9474
NDP52: 10241
miR-16: 406950///406951
let-7a: 406883///406882///406881"
  },
  {
    "caption": "(e) Quantification of fluorescence signal in AGO2 immunoprecipitates from HeLa cell extracts incubated with duplexes of let-7a-let-7a* labelled on the 3′ end of either let-7 or let-7a* with FITC. Cells were treated 16 h before with DMSO (control), BAF (200 nm) or geldanamycin (10 μM). Representative results of one experiment are shown.",
    "ncbi_link": "AGO2: 27161
let-7a: 406881///406883///406882
let-7a: 406882///406883///406881
let-7: 406883///406882///406881
let-7a: 406883///406882///406881"
  },
  {
    "caption": "(a) Renilla luciferase expression controlled by an exogenous siRNA-siRNA* duplex targeting two partially complementary sites in HeLa cells depleted of ATG5 or ATG7 with siRNA (black and grey bars correspond to two independent siRNAs). Results are normalized to firefly luciferase and Renilla luciferase expression in cells treated with a nonspecific siRNA-siRNA* duplex. n = 2 independent experiments.",
    "ncbi_link": "Renilla luciferase: 
firefly luciferase: 
ATG5: 9474
ATG7: 10533"
  },
  {
    "caption": "(b) Renilla luciferase expression controlled by let-7 in HeLa cells depleted of NDP52 or ATG5 with siRNA (black and grey bars are independent siRNAs). Results are normalized to firefly luciferase and a version of the Renilla luciferase construct with mutated let-7 binding sites. n = 3 independent experiments. The asterisks denote mutations in the let-7 target sites of the reporter.",
    "ncbi_link": "Renilla luciferase: 
firefly luciferase: 
ATG5: 9474
NDP52: 10241
let-7: 406882///406881///406883"
  },
  {
    "caption": "(c) Western blot analysis of endogenous miRNA-repressed proteins (RAS, HMGA2 and CDK6 are repressed by let-7; CDK6 is also repressed by miR-16 (bottom panel)) or control (TUBA, α-tubulin) in HeLa cells treated with control siRNA or either of two independent siRNAs targeting ATG7. Cells were treated in parallel with nonspecific antagomir or let-7 targeting antagomir.",
    "ncbi_link": "ATG7: 10533
miR-16: 406951///406950
let-7: 406882///406881///406883"
  },
  {
    "caption": "(d) Renilla luciferase expression controlled by the DICER 3′UTR in HeLa cells treated with control antagomir or anti-let-7 antagomir.",
    "ncbi_link": "Renilla luciferase: 
let-7: 406882///406881///406883"
  },
  {
    "caption": "(e) Western blot analysis of DICER in HeLa cells treated with control siRNA or either of two independent siRNAs targeting ATG7. Cells were also treated with nonspecific antagomir or let-7 targeting antagomir.",
    "ncbi_link": "ATG7: 10533
let-7: 406882///406881///406883"
  },
  {
    "caption": "(f) Renilla luciferase expression controlled by the DICER 3′UTR in HeLa cells treated with either of two independent siRNAs targeting ATG5 or a control siRNA. All error bars are s.e.m. Uncropped images of blots are shown in Supplementary Fig. S3.",
    "ncbi_link": "Renilla luciferase: 
ATG5: 9474"
  },
  {
    "caption": "(B) A fragment of genomic DNA (2.2 kb) was amplified by  PCR and in vitro sgRNA-guided  Cas9-mediated cleavage assay was performed with each of the sgRNAs. sgRNA-targeting sites are indicated by arrows, genomic DNA  size is indicated by asterisk.",
    "ncbi_link": "Cas9: 69900935"
  },
  {
    "caption": "F Cytochrome c  release from  mitochondria after exposure to  tBid  or BimBH3  peptide for parental  NB1643  and SY5Y  cells, in comparison to cells cultured in escalating concentrations of crizotinib until resistant (NB1643-ALKR and SY5Y-ALKR). Data information: data points are mean of duplicate wells (SD<0.05 at all points) in a representative experiment from at least two biological replicates.",
    "ncbi_link": "ALK: 238"
  },
  {
    "caption": "H In vitro viability of CHLA15-ctrl, CHLA15-shMFN2, CHLA15-shPACS2, and CHLA20 cells following 72hr exposure to ABT-737; dotted-line represents 50% viability. Data information: data points are mean and SD from triplicate wells, experiments are representative of at least two biological replicates.",
    "ncbi_link": "MFN2: 9927
PACS2: 23241"
  },
  {
    "caption": "I Mitochondrial cytochrome c  release in response to tBid  and BimBH3 peptide in CHLA15-Ctrl, CHLA15-shMFN2 and  CHLA15-shPACS2 cells. Data information: , data points are mean of duplicate wells (SD<0.05 at all points) in a representative experiment from at least two biological replicates",
    "ncbi_link": "MFN2: 9927
PACS2: 23241"
  },
  {
    "caption": "(A) Anti-acetyllysine Western blot analyses and total protein stains of E. coli cell extracts. Cellular protein extracts before and after induction of His6-MBP-GNAT expression were separated on 12 % acrylamide gels and immunoblotted by using an anti-acetyllysine antibody or stained with Coomassie Dye. GNAT1, 2, 5, 6, 7 and 10 as well as His6-MBP control were expressed in E. coli BL21(DE3)pLysS. GNAT3 and 4 were expressed in Rosetta(DE3). In the total protein stains, recombinant GNAT protein constructs were highlighted by blue arrowheads. Protein expression before (ni) and after (i) induction with IPTG is indicated. The luminescence signal, indicating acetylated proteins, was usually recorded after 40-120 seconds. Since MBP-GNAT4 expression resulted in a saturated signal, the luminescence was additionally recorded for 10 seconds (indicated by an asterisk).",
    "ncbi_link": "MBP: "
  },
  {
    "caption": "(C) Comparison of NTA yield of retrieved N-termini of proteins starting at position 1 or 2. The majority of these proteins, corresponding mostly to cytosolic components, undergoing or not to N-terminal methionine excision, were not affected by inactivation of GNAT2. For statistical analyses nsi-1 and nsi-2 were pooled and compared to the wild type. Two independent technical replicates of four biological replicates for each of the WT, nsi-1 and nsi-2 samples were analysed. Error bars are ± SD. (D) Comparison of NTA yield of retrieved N-termini of proteins starting at positions > 2. Clear alteration of NTA yield was observed in nsi mutant lines in the pool of nuclear-encoded plastid proteins. nsi-1 and nsi-2 samples were treated as in D. Error bars are ± SD (E) Comparison of NTA yields of retrieved N-termini in plastid proteins. Similar variation as in panel D was observed when NTA of only plastid proteins was analyzed.",
    "ncbi_link": "GNAT2: 835775"
  },
  {
    "caption": "B, Western blot showing no detectable Wbp2 protein in 4 week old mutant brain compared to wt littermate controls. 5μg of the protein lysate were subjected to 10% SDS-PAGE. β-tubulin was used as loading control. Wbp2 l and Wbp2 s refer to the long and short isoforms respectively.",
    "ncbi_link": "Wbp2: 22378"
  },
  {
    "caption": "C, Quantitative real-time PCR showing severe knockdown of Wbp2 transcription in 4 week old mutants (n=3) inner ears and eyes, compared to wt littermate controls (n=3). Heterozygotes show intermediate levels. Hprt was used as a control and levels are normalised to wt levels.",
    "ncbi_link": "Hprt: 
Wbp2: 22378"
  },
  {
    "caption": "D, F, X-gal staining of Wbp2 hets at P14 showing Wbp2 expression (blue) in all the main cochlear structures: the stria vascularis (black arrowhead in D), spiral prominence (empty arrowhead in D), Reissner's membrane (arrow in D), strong expression in the spiral ganglion cells (red arrowheads in E), IHCs and OHCs in the organ of Corti (arrowheads in F), pillar cells and spiral limbus (empty arrowhead in F). Scale bars: D: 50μm, E,F: 20μm. ihc: inner hair cells; ohc: outer hair cells. No X-gal staining is observed in wt controls (not shown). The X-gal reaction is always cytoplasmic.",
    "ncbi_link": "Wbp2: 22378"
  },
  {
    "caption": "B. Agarose gel trace of cDNA obtained from mouse wt P28 inner ear (IE), P28 brain, adult and P4 organ of Corti (OC). Results show expression of two Wbp2 isoforms in the brain at P28 and very faint band for the short isoform together with a strong band for the long isoform in the inner ear at P28. If we look at just the organ of Corti (adult and P4), we observe a strong band for the long isoform in the P4 OC and an almost undetectable band for the short isoform, which was not even picked up by sequencing (see C). Wbp2 l: long isoform (550 bp); Wbp2 s: short isoform (480 bp).",
    "ncbi_link": "Wbp2: 22378"
  },
  {
    "caption": "D. Western blot showing the predominant presence of the Wbp2 long isoform in the cochlea at P28, with a short trace of the short isoform showing up only when a higher concentration of protein lysate (20μg) is loaded. Both isoform are absent in the Wbp2-deficient mouse. Gapdh was used as a loading control. Wbp2 l: long isoform; Wbp2 s: short isoform.",
    "ncbi_link": "Wbp2: 22378"
  },
  {
    "caption": "A. At P14, afferent terminals below IHCs are slightly swollen in the mutants (neurofilament labelling in green, arrowheads to compare; CtBP2 labels ribbons and IHCnuclei in red). Scale bars: 10 μm. At P28,Neurofilament/CtBP2 labelling in the organ of Corti of 4 week old Wbp2-deficient mice and littermate controls shows severe swelling of IHCafferent terminals in the mutants, especially in the 24kHz region (yellow arrowheads). The pre-synaptic ribbons do not look as well aligned to the terminals in the mutants (white arrows). At this stage, we also observe swelling of OHCafferent terminals in the 24kHz region (empty arrowheads). Scale bars: 5 μm. ihc: IHCnucleus; p: pillar side; m: modiolar side.B. Counts of pre-synaptic ribbons per IHC in the 8, 18 and 24kHz regions, showing no difference between mutants and controls at P28.",
    "ncbi_link": "Wbp2: 22378"
  },
  {
    "caption": "B, Quantitative real-time PCR showing reduced mRNA levels for Esr1, Esr2 and Pgr and upregulation of Shank3 and Psd-95 in cochleae of 4 week old Wbp2-deficient mice compared to littermate controls (n=3 for each genotype). Hprt is used as relative control. Error bars: ±SD. Two-tailed student t test: p=0.03 for Psd-95; p=0.007 for Shank3; p=0.03 for Esr2; p=0.0016 for Esr1; p=0.037 for Pgr.",
    "ncbi_link": "Hprt: 
Psd-95: 13385
Esr1: 13982
Esr2: 13983
Pgr: 18667
Shank3: 58234
Wbp2: 22378"
  },
  {
    "caption": "(B-C) Non-overlapping patterns of old (green) versus new (red) histone H3 (B) and overlapping patterns for H2A (C) in mitotic prometaphase bam mutant cells marked by anti-H3S10p (gray), similar to WT GSCs. Scale bars: 2μm.",
    "ncbi_link": "bam: 43038"
  },
  {
    "caption": "(F-H) Examples showing old (green) versus new (red) H3 distribution patterns and percentage of signal strength at a single genomic locus labeled with fluorescent probes (gray) for dad gene (F), bgcn gene (G), and ss gene (H) in bam mutant GSC-like cells at prometaphase marked by anti-H3S10p (blue). Scale bars: 1μm. Zoomed-in images of each probe are displayed to the right of each figure panel. Scale bars: 0.1μm.",
    "ncbi_link": "bam: 43038
bgcn: 47873
dad: 42059
ss: 41988"
  },
  {
    "caption": "(A-B) Old (red) versus new (green) histone H3 distribution patterns and percentage of signal strength with a single genomic locus labeled with fluorescent probes (cyan) for dad (A) and bam (B) in WT telophase female GSCs, marked by anti-H3S10p (gray). (C) Quantification of the probe association ratios with old versus new H3 for each candidate gene in WT female GSCs. Data gathered over 8 separate experiments. D ",
    "ncbi_link": "bam: 43038
dad: 42059"
  },
  {
    "caption": "The cRQ values from RT-qPCR of indicated cells. Total RNA was extracted and CD137 mRNA levels measured relative to that from HEK293T cells. Conjugated OptoCARCD19‑T cells were also assayed either before or after 24 hours stimulation in the dark state. Individual values from three biological replicates are shown, with mean depicted by bar plot.",
    "ncbi_link": "CD19: 930
CD137: 21942"
  },
  {
    "caption": "A Immunoblot analysis of overexpressed and ALFA-tagged CNX in CNX knockout cell lines clones #1 and #2, which were used for mass spectrometry. Endogenous CNX level of wildtype HEK293T cells is shown as a control.",
    "ncbi_link": "ALFA: 
CNX: 821"
  },
  {
    "caption": "C Volcano plots derived from LC-MS/MS analyses of ALFA-tagged CNX, immunoprecipitated in 1% NP-40 buffer from transfected CNX deficient HEK293T cells after DSSO crosslinking and compared to empty vector (EV) control co-IPs. Depicted is an enlarged section of the associated complete volcano plot in the upper right. Among the significantly enriched proteins, annotations are Uniprot gene names. CNX is shown in green. ER proteins with the GO-term annotation \"endoplasmic reticulum\", which are localized to the ER lumen, are highlighted in blue and among those several known CNX interaction partners are indicated with their names. Membrane proteins are shown in red and those which are non-glycosylated are additionally labeled with their gene names.",
    "ncbi_link": "ALFA: 
CNX: 821"
  },
  {
    "caption": "E Co-immunoprecipitations of endogenous CNX with FLAG-tagged Cx32 WT and its mutants including quantification and statistical analysis. Constructs were expressed in HEK293T cells. One representative immunoblot is shown. Monomers and dimers of Cx32 are indicated with brackets. All samples were normalized to WT",
    "ncbi_link": "FLAG: 
Cx32: 2705"
  },
  {
    "caption": "F Immunofluorescence images of Cx32 and its mutants. COS-7 cells were transiently transfected with the indicated FLAG-tagged Cx32 constructs and immunofluorescence microscopy was performed using anti PDI (green) as an ER marker. Detection of Cx32 was performed using anti FLAG antibodies and suitable labeled secondary antibodies (red). Nuclei were stained with DAPI (blue). All three channels are overlayed. Images are representative of cells from at least three different biological replicates. GJ denotes gap junctions observed at cell-cell junctions of cells transfected with WT Cx32.",
    "ncbi_link": "FLAG: 
Cx32: 2705"
  },
  {
    "caption": "C Interaction analysis of Calnexin with the first transmembrane domain of Cx32. Intracellular BMH crosslinking of transiently transfected V5-tagged CNX with the transiently transfected R26C mutant of Cx32-TMD1. In the AA mutant of CNX, the two cysteines within the CNX TMD were replaced by alanines. The species at approx. 250 kDa are possibly CNX dimers.",
    "ncbi_link": "V5: 
CNX: 821
Cx32: 2705"
  },
  {
    "caption": "F Interaction of Cx32-TMD1 with the minCNX system. MinCNXTMD constructs and controls (see (D)) were co-transfected with Cx32-TMD1 into HEK293T cells. Interaction between the proteins was analyzed by co-immunoprecipitation experiments followed by immunoblotting.",
    "ncbi_link": "Cx32: 2705"
  },
  {
    "caption": "B HEK293T cells were transiently transfected with plasmids expressing ConMem or the indicated variants, where either the first (N1) or the second (N2) NVT glycosylation motif was ablated (N to Q mutation). Lysates were treated with or without EndoH or PNGaseF as indicated, and analyzed by immunoblotting. N-glycosylation occurs in the ER, complex glycosylation in the Golgi.",
    "ncbi_link": "ConMem: "
  },
  {
    "caption": "B Representative blots from co-immunoprecipitation experiments from HEK293T cells transfected with the indicated ConMem constructs with or without ER-lumenal glycosylation site (N1) (mean ± SEM, N = 3, *P value < 0.05, two-tailed Student's t tests). Individual values were normalized to ConMem N1Q (Val) values that were set to 1.",
    "ncbi_link": "ConMem: "
  },
  {
    "caption": "C Interaction of ConMem N1Q variants as described in (A) with endogenous CNX (mean ± SEM, N ≥ 5, *P value < 0.05, two-tailed Student's t tests ). Individual values were normalized to ConMem N1Q (Val) values that were set to 1. D Same as in (C) only that selected amino acids (proline and arginine) where shifted through the ConMem N1Q TMD segment to five different positions as shown in the illustration, revealing positional binding dependencies (mean ± SEM, N ≥ 4, *P value < 0.05, two-tailed Student's t tests). Individual values were normalized to ConMem N1Q (Val) values that were set to 1.",
    "ncbi_link": "ConMem: "
  },
  {
    "caption": "D Interaction of non-glycosylated ConMem N1Q constructs with V5-tagged CNX. In CNX variants, amino acids important for interaction as revealed in (A) were replaced by valine residues. HEK293T cells were transiently transfected with the indicated constructs and cell lysates and HA-immunoprecipitates were analyzed for HA-tagged ConMem N1Q and co-immunoprecipitating CNX mutants. E The same as in (D) for Cx32-TMD1 F Analysis of mutations in the CNX TMD region and their effect on binding glycosylated ConMem. G The same as in (D) for Cx32 full-length",
    "ncbi_link": "ConMem: 
CNX: 821"
  },
  {
    "caption": "H Interaction of Cx32-TMD1 with CNX mutants, where amino acids not predicted to be important for interaction as shown in (A) were exchanged by valine residues. HEK293T cells were transiently transfected with the indicated constructs.",
    "ncbi_link": "CNX: 821"
  },
  {
    "caption": "A Analysis of the interaction of the binding deficient CNX YTL TMD variant with Rhodopsin. CNX knockout HEK293T cells were transiently transfected with either N-terminal ALFA-tagged Rhodopsin alone or in combination with the indicated V5-tagged CNX constructs. In the absence of any CNX, Rho is hardly detectable (long exposure shown). Cell lysates and ALFA-immunoprecipitates were analyzed for Rhodopsin and co-immunoprecipitating CNX.",
    "ncbi_link": "ALFA: 
V5: 
CNX: 821
Rhodopsin: 6010"
  },
  {
    "caption": "B Analysis of Rhodopsin degradation and its dependency on CNX. CNX knockout HEK293T cells that were transfected with the indicated constructs were incubated with cycloheximide and lysates were collected at different timepoints. CNX WT and CNX YTL immunoblots are from the same blot (dashed line), showing similar expression levels. Hsc70 was used as a loading control (also from the same blot, dashed line). Quantifications are shown below representative immunoblots",
    "ncbi_link": "CNX: 821"
  },
  {
    "caption": "Sanger sequencing chromatograms showing the homozygous M1AP splicing mutation in patients and heterozygous mutation in their fertile brother. The arrowhead indicates the position of the mutation.",
    "ncbi_link": "M1AP: 130951"
  },
  {
    "caption": "Immunofluorescence staining of M1AP (green) and SYCP3 (red) on spermatocyte spreads of WT or Spo11-/- mice.",
    "ncbi_link": "Spo11: 26972"
  },
  {
    "caption": "Testicular histology from 8-week-old control and M1apKI/KI mice. The magnified view of the boxed area is shown in the lower left corner of the image of M1apKI/KI mice. The blue arrow indicates unaligned chromosomes in the representative metaphase cells.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "The mean number of MSH4 foci per nucleus in control and M1apKI/KI spermatocytes at the indicated stages.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "The mean number of RAD51 foci per nucleus in control and M1apKI/KI spermatocytes at the indicated stages.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "The mean number of DMC1 foci per nucleus in control and M1apKI/KI spermatocytes at the indicated stages.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "Immunofluorescence staining with antibodies against SYCP3 (red) and MLH3 (green) on oocyte spreads from control and M1apKI/KI embryos (18.5 dpc). Number of MLH3 foci per cell in control and M1apKI/KI oocytes.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "Representative haemotoxylin-stained ovarian sections of 5-dpp-old control and M1apKI/KI mice. Follicle counts and total oocyte counts per ovary at 5 dpp.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "Co-IP using anti-M1AP antibody with whole-testis lysates of WT mice and M1ap-/- mice, followed by western blot analyses of M1AP, SHOC1, and TEX11.",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "Co-IP detecting the interaction between M1AP (fused with an N-terminal MYC tag) and each of the ZZS complex components (fused with an N-terminal GFP tag) exogenously expressed in HEK-293T cells.",
    "ncbi_link": "GFP: 
MYC: "
  },
  {
    "caption": "Immunofluorescence staining of TEX11 (green) and SYCP3 (red) on the spermatocyte spreads of control and M1apKI/KI testes.   The mean number of TEX11 foci per cell in control and M1apKI/KI spermatocytes.   Frequencies of nuclei with TEX11 foci detected at the PAR in spread early pachytene spermatocytes with touching XY chromosomes.  ",
    "ncbi_link": "M1ap: 110958"
  },
  {
    "caption": "B. Comparisons of MTAP mRNA and protein expression between CL1-0 and CL1-5 cells detected by RT-qPCR (top, mean ± SD, Student t test, n=3, biological replicates, *p < 0.05) and Western blot assays using anti-MTAP antibody (bottom, representative of three independent experiments).",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "C. Cell invasion abilities of MTAP-overexpressing CL1-5 or MTAP-knockout CL1-0 and H1650 were determined by Boyden chamber invasion assays (mean ± SD, Student t test, n=3, biological replicates, *p < 0.05). sgCTRL indicates cells transduced with a non-targeting control sgRNA, and sgMTAP indicates cells transduced with a sgRNA targeting MTAP. Bottom: the protein expression levels of V5-MTAP and endogenous MTAP were detected by Western blots.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "E. Effect of MTAP overexpression on lung cancer metastasis in vivo was demonstrated by orthotopic implantation assays. Top: representative photographs of lungs and H&E staining of the lung sections. The primary tumors are indicated by arrowheads and the metastatic nodules are indicated by arrows. Bottom: quantification of averaged primary tumor sizes, metastatic incidence and nodule number.",
    "ncbi_link": "MTAP: 66902"
  },
  {
    "caption": "F. Kaplan-Meier analyses of overall survival (top) and progression-free survival (bottom) for 101 patients with lung adenocarcinoma grouped into high- or low-MTAP mRNA expression measured by RT-qPCR. p values were obtained by log-rank test.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "A. The necessity of MTAP activity in cell invasion. CL1-5 and A549 cells were introduced with indicated plasmids and subjected to Boyden chamber invasion assays (mean ± SD, Student t test, n=3, biological replicates, *p < 0.05 compared to the vector control group). The protein expression levels of exogenous wild-type and mutant V5-MTAP were detected by Western blots.",
    "ncbi_link": "V5: 
MTAP: 4507"
  },
  {
    "caption": "B. Western blot analysis of the symmetric dimethylarginine (sDMA), monomethylarginine (mMA) and asymmetric dimethylarginine (aDMA) levels in MTAP-overexpressing and MTAP-knockout cells. V5-MTAP wild-type and D220A mutant were restored in H1650 MTAP-knockout cells. Data shown are representative of three independent experiments.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "D. Immunoprecipitation analysis for vimentin dimethylation in response to PRMT5 knockdown in H1650 cells. Arrow marks dimethyl-vimentin. Data shown are representative of three independent experiments.",
    "ncbi_link": "PRMT5: 10419"
  },
  {
    "caption": "E-F. Immunoprecipitation analysis for vimentin dimethylation in control and MTAP-knockout cells. Arrows mark vimentin, asterisks mark heavy chains, and arrowheads mark nonspecific bands. Data shown are representative of three independent experiments.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "G. Vimentin-knockdown counteracts MTAP-loss-induced effect on cell invasion. MTAP-knockout and control H1650 cells were transfected with vimentin-specific siRNAs for 72 hours and analyzed by Boyden chamber invasion assays (mean ± SD, Student t test, n=3, biological replicates, *p < 0.05). The silence efficiency of vimentin was examined by Western blots.",
    "ncbi_link": "MTAP: 4507
Vimentin: 7431
vimentin: 7431"
  },
  {
    "caption": "F. Validation of the PRMT5-catalyzed methylation sites on V5-vimentin. HEK293T cells were transfected with indicated constructs and subjected to immunoprecipitation analysis. The intensity of sDMA signals was quantified by ImageJ software, normalized to the intensity of corresponding immunoprecipitated V5-vimentin, then relative to the V5-vimentin wild-type group and represented as percentage. Data were the averaged percentage from three independent experiments.",
    "ncbi_link": "V5: 
vimentin: 7431"
  },
  {
    "caption": "B. Reconstitution of vimentin-knockout cells with wild-type, 4RK- and 4RF-mutated V5-vimentin. Both protein and mRNA levels of vimentin were determined by Western blots and RT-qPCR. Data shown are representative of three independent experiments.",
    "ncbi_link": "vimentin: 7431"
  },
  {
    "caption": "E. Western blot analysis of vimentin protein levels in MTAP-knockout and control cells transfected with PRMT5 siRNAs (left) or Flag-PRMT5 (right). Arrows mark the site of Flag-PRMT5 and endogenous PRMT5. Data shown are representative of three independent experiments.",
    "ncbi_link": "Flag: 
MTAP: 4507
PRMT5: 10419"
  },
  {
    "caption": "F. Effect of PRMT5 on the levels of ectopically expressed wild-type, 4RK- and 4RF-mutated V5-vimentin in HEK293T cells assessed by Western blots. Data shown are representative of three independent experiments. G. Effects of wild-type and catalytically dead R368A mutant PRMT5 on the level of V5-vimentin in HEK293T cells detected by Western blot assays. Data shown are representative of three independent experiments.",
    "ncbi_link": "V5: 
PRMT5: 10419
vimentin: 7431"
  },
  {
    "caption": "A. Measurement of V5-vimentin wild-type, 4RK and 4RF mutant protein levels in CL1-5 vimentin-knockout cells treated with 10 μM MG132 by Western blots. Data shown are representative of three independent experiments.",
    "ncbi_link": "vimentin: 7431"
  },
  {
    "caption": "B. Western blot analysis of vimentin protein levels in control and MTAP-knockout cells treated with 10 μM MG132. Data shown are representative of three independent experiments.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "Immunoprecipitation analysis of ubiquitination (C) of V5-vimentin in HEK293T cells transfected with wild-type, 4RK- or 4RF-mutated vimentin in the presence of HA-tagged ubiquitin. Arrows mark the sites of V5-vimentin. Data shown are representative of three independent experiments.",
    "ncbi_link": "vimentin: 7431"
  },
  {
    "caption": "K48-linked polyubiquitination (D) of V5-vimentin in HEK293T cells transfected with wild-type, 4RK- or 4RF-mutated vimentin in the presence of HA-tagged ubiquitin. Arrows mark the sites of V5-vimentin. Data shown are representative of three independent experiments.",
    "ncbi_link": "vimentin: 7431"
  },
  {
    "caption": "E. Immunoprecipitation analysis for K48-linked polyubiquitination of vimentin in CL1-0 control and MTAP-knockout cells. Arrow marks the site of vimentin. Data shown are representative of three independent experiments.",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "F-G. Western blot analysis of V5-vimentin wild-type, 4RK and 4RF mutant levels in CL1-0 cells (F) or endogenous vimentin levels in control and MTAP-knockout cells (G) treated with 50 μg/ml cycloheximide (CHX). Bottom: the intensity of V5-vimentin and vimentin signals was quantified by ImageJ software, normalized to the internal control β-actin, then normalized to zero time point, and plotted against time points (mean ± SE, n=3, biological replicates).",
    "ncbi_link": "MTAP: 4507"
  },
  {
    "caption": "(B) The transcripts of ferroptosis-associated markers were determined by qPCR using iRPE cells as the template. The RNA extract from untreated iRPE was included as the control. The level of each transcript was normalized to ACTB. The statistics are analyzed by ratio paired student's t-test for each target gene. The results are presented as mean ± S.E.M., n = 3 iRPE lines for each group. * p < 0.05; ** p < 0.01. Round dots: untreated iRPE; square dots: DFO-treated iRPE.",
    "ncbi_link": "ACTB: 60"
  },
  {
    "caption": "(A) Levels of KRAS, COUP-TFII, LDHA, and phosphorylated S6K (T389) in KRASWT, KRASG12D, and KRAS-silenced KRASG12D MEF cells.",
    "ncbi_link": "KRAS: 16653"
  },
  {
    "caption": "(B) Extracellular acidification rate (ECAR) in KRASWT, KRAS G12D, and KRAS- or COUP-TFII-silenced KRAS G12D MEF cells.",
    "ncbi_link": "KRAS: 16653
COUP-TFII: 11819"
  },
  {
    "caption": "(C) Lactate levels in MEF cells Data are expressed as the mean ± SEM of three independent experiments and normalized against values measured in KRASWT MEF. ***p<0.001.",
    "ncbi_link": "KRAS: 16653"
  },
  {
    "caption": "(D) Levels of COUP-TFII, LDHA, and phosphorylated S6K (T389) in COUP-TFII-silenced KRASG12D MEF cells.",
    "ncbi_link": "KRAS: 16653
COUP-TFII: 11819"
  },
  {
    "caption": "(A) Levels of KRAS, COUP-TFII, LDHA, and phosphorylated S6K (T389) in KRAS-silenced HCT116 and DLD-1 cells.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "(B) Levels of COUP-TFII, LDHA, and phosphorylated S6K (T389) in COUP-TFII-silenced HCT116 and DLD-1 cells.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(C) Effect of lactate on phosphorylated S6K (T389), 4E-BP1 (T37/46), ULK1 (S757) in COUP-TFII-silenced HCT116 cells.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(D) Effects of COUP-TFII and the inhibition of LDHA on phosphorylated S6K (T389) and Raptor (S792) in KRAS-silenced HCT116 cells. Asterisk indicates exogenous HA-COUP-TFII. Arrow indicates phosphorylated Raptor (S792).",
    "ncbi_link": "KRAS: 3845
COUP-TFII: 7026"
  },
  {
    "caption": "(E) Inhibition of COUP-TFII-silenced HCT116, DLD-1, and MIA PaCa-2 cell proliferation and its recovery by treatment with lactate. Data are expressed as the mean ± SEM of three independent experiments and normalized against values measured in control. *p<0.05, **p<0.01, and ***p<0.001.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(F) Clonogenic assay of COUP-TFII-silenced HCT116, DLD-1, and MIA PaCa-2 cells in the presence or absence of lactate.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(B) Effect of lactate on phosphorylated S6K (T389) inhibited by TSC2 overexpression in HCT116 cells.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(C) Molecular interaction between TSC2 and Rheb in the presence or absence of lactate in HA-Rheb-overexpressing HCT116 cells after serum deprivation overnight.",
    "ncbi_link": "HA: 
Rheb: 6009"
  },
  {
    "caption": "(A) Interaction between endogenous TSC2 and Rheb in the presence or absence of lactate in COUP-TFII-silenced HCT116 cells.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(B) Effect of lactate on Rheb activation in COUP-TFII-silenced HCT 116 cells.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(D) Molecular interaction between TSC2 and Rheb in the presence or absence of lactate in HA-Rheb- and/or COUP-TFII-overexpressing HCT116 cells treated with 25 nM trametinib for 24 h.",
    "ncbi_link": "HA: 
COUP-TFII: 7026
Rheb: 6009"
  },
  {
    "caption": "(E) Effects of lactate and COUP-TFII overexpression on Rheb activation in HCT116 cells treated with 25 nM trametinib for 24 h.",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "Effects of COUP-TFII inhibition and lactate treatment on tumor growth in vivo. (A) Growth curve in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(B) tumor volume at the experimental endpoint, in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "Effects of COUP-TFII inhibition and lactate treatment on tumor growth in vivo. (C) Western blot analysis of the indicated proteins in tumors derived from xenografted shScramble or shCOUP-TFII-HCT116 cells and treated with sodium chloride or sodium L-lactate (60 l x g-1 body weight; 150 mM).",
    "ncbi_link": "COUP-TFII: 7026"
  },
  {
    "caption": "(D) Effects of trametinib treatment and overexpression of COUP-TFII on tumor growth in vivo. Tumors were derived from xenografted HCT116 expressing HA-COUP-TFII or carrying a control vector and treated with trametinib (3mg/kg).",
    "ncbi_link": "HA: 
COUP-TFII: 7026"
  },
  {
    "caption": "(E) Western blot analysis of indicated proteins in tumors derived from xenografted HCT116 treated with trametinib with or without COUP-TFII overexpression. Asterisk indicates exogenous HA-COUP-TFII.",
    "ncbi_link": "HA: 
COUP-TFII: 7026"
  },
  {
    "caption": "(A) Representative images of HEK293-T cells transfected with GFP (top), GFP-Teneurin4WT (GFP-Ten4WT; middle) or GFP- Teneurin4Mut (GFP-Ten4Mut; bottom) for 24h and stained with Alexa 568 Phalloidin (magenta) and Dapi (blue). Images are maximum intensity projections of 14-16 stacks. Scale bar, 10 µm. (B) Zoom shows the regions indicated in A. White arrows indicate the tip of the filopodium from the transfected cell. Scale bar, 2 µm. (",
    "ncbi_link": "GFP: 
Teneurin4: 26011"
  },
  {
    "caption": "(C) Average number of filopodia per cell in cells transfected with GFP, GFP-Teneurin4WT (Ten4 WT; red) and GFP- Teneurin4Mut (Ten4Mut; blue). (D) Fraction of filopodia enriched with GFP per cell in GFP-, GFP-Teneurin4WT (Ten4WT; blue)- and GFP-Teneurin4Mut (Ten4Mut; red)-transfected cells. (",
    "ncbi_link": "GFP: 
Teneurin4: 26011"
  },
  {
    "caption": "(A) Representative images of non-adherent K562 cells electroporated with GFP (left), GFP-Teneurin4WT (GFP-Ten4WT; middle) or GFP-Teneurin4Mut (GFP-Ten4Mut; right). Zoomed images show the formation of cellular clusters in cells expressing GFP-Ten4WT and GFP-Ten4Mut, but not in GFP-expressing cells. Scale bar top panel, 50 µm. Scale bar bottom panel, 20 µm.",
    "ncbi_link": "GFP: 
Teneurin4: 26011"
  },
  {
    "caption": "(C) Fraction of cell clusters detected per image in GFP- (black), GFP-Teneurin4WT (blue)- and GFP-Teneurin4Mut (red)-electroporated cells.",
    "ncbi_link": "GFP: 
Teneurin4: 26011"
  },
  {
    "caption": "A-D SQST‐1::GFP is very weakly expressed and diffusely localized in the cytoplasm in wild‐type larval intestine, but is expressed at much higher levels and accumulates into numerous aggregates in the intestine in bp399 mutant larvae. (A) and (C) represent DIC images of the animals in (B) and (D), respectively.",
    "ncbi_link": "bp399: 175070"
  },
  {
    "caption": "E Compared to wild‐type, SQST‐1::GFP levels are much higher in bp399 and bp412 mutant larvae as shown by immunoblotting assay. SQST‐1::GFP levels in bp399 mutants are greatly reduced after 12 h of starvation. 200 young adult animals for each genotype were collected for analysis.",
    "ncbi_link": "bp412: 176921
bp399: 175070"
  },
  {
    "caption": "H, I SQST‐1::GFP aggregates in rpl‐43(bp399) mutants are separable from LAAT‐1::Cherry‐labeled lysosomes under normal conditions, but are delivered to lysosomes upon starvation. Some aggregates are enclosed by lysosomes (inserts). Scale bar: 20 μm.",
    "ncbi_link": "rpl‐43: 175070"
  },
  {
    "caption": "J-Q RNAi inactivation of let‐363, rpn‐2, cogc‐1, or hgrs‐1 suppresses the accumulation of SQST‐1::GFP aggregates in rpl‐43(bp399) mutants. (J), (L), (N), and (P): DIC images of the animals in (K), (M), (O), and (Q). Scale bar: 20 μm.",
    "ncbi_link": "cogc‐1: 3565555
hgrs‐1: 177617
let‐363: 172167
rpl‐43: 175070
rpn‐2: 175877"
  },
  {
    "caption": "R SQST‐1::GFP levels in rpl‐43(bp399) mutants are greatly reduced by inactivation of rpt‐3 and rpn‐2. 200 young adult animals for each genotype were collected for analysis.",
    "ncbi_link": "rpl‐43: 175070
rpn‐2: 175877
rpt‐3: 178988"
  },
  {
    "caption": "A, B SQST‐1::GFP aggregates are absent in the rpl‐43(bp399); sma‐3(wk20) mutant intestine.",
    "ncbi_link": "rpl‐43: 175070
sma‐3: 175955"
  },
  {
    "caption": "C Percentage of the indicated animals with different levels of SQST‐1::GFP aggregates. S: many SQST‐1::GFP aggregates in all intestinal cells, as in rpl‐43(bp399) mutants; M: fewer SQST‐1::GFP aggregates in some but not all intestinal cells; N: no or very few SQST‐1::GFP aggregates in intestinal cells. For each genotype, > 30 animals were examined.",
    "ncbi_link": "rpl‐43: 175070"
  },
  {
    "caption": "D SQST‐1::GFP levels in rpl‐43(bp399) mutants are dramatically decreased in a Western blot when sma‐3, lin‐35, or daf‐2 is simultaneously depleted. Loss of function of daf‐16 partially restores SQST‐1 levels in rpl‐43(bp399); daf‐2(RNAi) mutants.",
    "ncbi_link": "daf‐16: 172981
daf‐2: 175410
lin‐35: 172249
rpl‐43: 175070
sma‐3: 175955"
  },
  {
    "caption": "E Endogenous LGG‐1 is elevated in a Western blot in dbl‐1(wk70), sma‐2(e502), and sma‐3(wk20) mutants.",
    "ncbi_link": "dbl‐1: 179068
sma‐2: 176229
sma‐3: 175955"
  },
  {
    "caption": "F mRNA levels of bec‐1, epg‐8, lgg‐1, and atg‐7 are upregulated in dbl‐1(wk70), sma‐2(e502), and sma‐3(wk20) mutants. **P 0.01. 500 young adult animals were collected for analysis. Error bars indicate s.d. from three experiments.",
    "ncbi_link": "atg‐7: 178005
bec‐1: 177345
dbl‐1: 179068
epg‐8: 172847
lgg‐1: 174050
sma‐2: 176229
sma‐3: 175955"
  },
  {
    "caption": "G, H No SQST‐1::GFP aggregates are observed in the lin‐35(n745); rpl‐43(bp399) mutant intestine.",
    "ncbi_link": "lin‐35: 172249
rpl‐43: 175070"
  },
  {
    "caption": "I, J Numerous SQST‐1::GFP aggregates are formed in rpl‐43(bp399); lin‐15A(n767) mutants.",
    "ncbi_link": "lin‐15A: 181663
rpl‐43: 175070"
  },
  {
    "caption": "K Endogenous LGG‐1 levels are increased in lin‐9(n112), lin‐15B(n744), and lin‐35(n745) mutants.",
    "ncbi_link": "lin‐15B: 181662
lin‐35: 172249
lin‐9: 176256"
  },
  {
    "caption": "L mRNA levels of bec‐1, epg‐8, lgg‐1, and atg‐7 are upregulated in lin‐9(n112), lin‐15B(n744), and lin‐35(n745) mutants. **P 0.01. 500 young adult animals were collected for analysis. Error bars indicate s.d. from three experiments.",
    "ncbi_link": "atg‐7: 178005
bec‐1: 177345
epg‐8: 172847
lgg‐1: 174050
lin‐15B: 181662
lin‐35: 172249
lin‐9: 176256"
  },
  {
    "caption": "M, N rpl‐43(bp399); daf‐2(RNAi) mutant larvae contain no intestinal SQST‐1::GFP aggregates.",
    "ncbi_link": "daf‐2: 175410
rpl‐43: 175070"
  },
  {
    "caption": "O, P SQST‐1::GFP aggregates are partially restored in daf‐16(mu86); rpl‐43(bp399); daf‐2(RNAi) animals.",
    "ncbi_link": "daf‐16: 172981
daf‐2: 175410
rpl‐43: 175070"
  },
  {
    "caption": "D, E Phsp‐4::GFP expression is much higher in rpt‐3(RNAi) animals.",
    "ncbi_link": "rpt‐3: 178988"
  },
  {
    "caption": "F, G Upregulation of Phsp‐4::GFP expression in rpt‐3(RNAi) animals is suppressed by the xbp‐1(zc12) mutation.",
    "ncbi_link": "rpt‐3: 178988
xbp‐1: 175541"
  },
  {
    "caption": "H, I SQST‐1::GFP aggregates are absent in rpl‐43(bp399); rpt‐3(RNAi) animals.",
    "ncbi_link": "rpl‐43: 175070
rpt‐3: 178988"
  },
  {
    "caption": "J, K Loss of function of xbp‐1 restores SQST‐1::GFP aggregates in rpl‐43(bp399); rpt‐3(RNAi) animals.",
    "ncbi_link": "rpl‐43: 175070
rpt‐3: 178988
xbp‐1: 175541"
  },
  {
    "caption": "M The increase in bec‐1, epg‐8, lgg‐1, and atg‐7 mRNA levels in npl‐4.1, rpt‐3, and pep‐2 RNAi animals is dependent on xbp‐1. *P 0.05, **P 0.01. 500 young adult animals were collected for analysis. Error bars indicate s.d. from three experiments.",
    "ncbi_link": "atg‐7: 178005
bec‐1: 177345
epg‐8: 172847
pep‐2: 172167
lgg‐1: 174050
npl‐4.1: 173952
rpt‐3: 178988
xbp‐1: 175541"
  },
  {
    "caption": "B egl‐46(RNAi) causes upregulation of Phsp‐60::GFP.",
    "ncbi_link": "egl‐46: 179058"
  },
  {
    "caption": "E, F Loss of function of atfs‐1 suppresses the upregulation of Phsp‐60::GFP in egl‐46(n1126) mutants. (E): DIC image of (F).",
    "ncbi_link": "atfs‐1: 179922
egl‐46: 179058"
  },
  {
    "caption": "G, H The dramatic decrease in the number of SQST‐1::GFP aggregates in the intestine in rpl‐43(bp399); egl‐46(RNAi) mutants (G) is restored by simultaneous loss of function of atfs‐1(gk3094) (H).",
    "ncbi_link": "atfs‐1: 179922
egl‐46: 179058
rpl‐43: 175070"
  },
  {
    "caption": "I, J GFP::LGG‐1 forms numerous puncta in the intestine in egl‐46(RNAi) (I), gfi‐1(RNAi) (J) animals.",
    "ncbi_link": "egl‐46: 179058
gfi‐1: 179022"
  },
  {
    "caption": "C Graphs show the quantification of lamin B1 intensity and circularity in 30-week-old R6/1 mouse striatal neurons nuclei with (mHtt +) or without (mHtt -) nuclear inclusions. N = 6. EM48 antibody was used to label mHtt inclusions. Representative images are shown. Scale bar 7 μm.",
    "ncbi_link": "mHtt: 15194"
  },
  {
    "caption": " A Graphs show the quantification of lamin B1 intensity and circularity. N = 3. An average of 12 nuclei was examined in each culture. Data are expressed as a percentage of controls. Bars represent the mean ± S.E.M. *P < 0.05 and **P < 0.01 as compared to mApple-C1 control neurons (two-tailed unpaired Student's t test). Exact P values are reported in Appendix Table S3. B Representative images showing primary striatal neurons transfected with mApple-C1 or with mApple-LB1, both in red. Neuronal nuclei were stained with DAPI-Fluoromount G (blue). Lamin B1 is shown in white. Scale bar 10 μm. ",
    "ncbi_link": "mApple: 
LB1: 4001"
  },
  {
    "caption": " D Lamin B1 enrichment in common, wild-type (WT, N=3) specific (spec) and R6/1 (N=3) specific LADs (log10(LB1/Input reads +1) in hippocampus (Hipp; left). Bar graphs of significant (Benjamini's adjusted P-value < 0.05) Biological Processes terms from DAVID for genes within common and WT specific LADs (right). Gene-term enrichment was estimated by DAVID using a modified Fisher's exact test and Benjamini multiple correction test. Bars represents the -log10 (Benjamini's adjusted P-value). Exact P values are reported in Appendix Table S3. E Representaive immunoblot showing lamin B1 levels in the nucleoplasm (Nucleop) and chromatin (Chrom) in the hippocampus of 30-week-old wild-type (WT, N = 7) and R6/1 (N = 7) mice. TBP, TATA binding protein. ",
    "ncbi_link": "Lamin B1: 16906
LB1: 16906"
  },
  {
    "caption": " B UCSC genome browser capture of wild-type (WT, N=3) and R6/1 (N=3) mice hippocampus ATAC-seq data, hippocampal H3K9ac and unchanged, closed in R6/1 and open in R6/1 accessible detected regions (left) in Tuba1α, Gabra2α and Dlx2 gene locus. Arrows in blue (closed in R6/1) and red (open in R6/1) indicate differential accessible regions. Bar graphs of significant (Benjamini's adjusted P-value < 0.05) Biological Processes terms from DAVID for genes associated with decreased (right top) or increased (right bottom) chromatin accessibility regions. Gene-term enrichment westimated by DAVID using a modified Fisher's exact test and Benjamini multiple correction test. Bars represents the -log10 (Benjamini's adjusted P-value). Exact P values are reported in Appendix Table S3. ",
    "ncbi_link": "Dlx2: 13392
Gabra2α: 14395
Tuba1α: 22142"
  },
  {
    "caption": " E UCSC genome browser capture of wild-type (WT, N=3) and R6/1 (N=3) mice hippocampus ATAC-seq data, lamin B1 ChIP-seq (log(Lb1 ChIP/Input)) for WT (N=3) and R6/1 (N=3) mice hippocampus, hippocampal H3K9ac, CTCF and H3K9me3 for WT mice hippocampus in Fos locus (left). Enhancer regions (E1-E5) are indicated with arrows. Boxplot of lamin B1 enrichment (log10(Lb1 ChIP/Input)) for regions with unchanged, decreased (closed in R6/1) and increased (opened in R6/1) chromatin accessibility in R6/1 (N=3) mice hippocampus. * P < 0.05 as compared to WT (N=3) mice. (Wilcoxon Mann Whitney test). Exact P values are reported in Appendix Table S3. The bottom and top of the boxes are the first and third quartiles, and the line within represents the median. The whiskers denote the interval within 1.5 times the interquartile range (IQR) from the median. ",
    "ncbi_link": "CTCF: 13018
Fos: 14281"
  },
  {
    "caption": "(A) Confocal microscopy image analysis of sEV fusion to MGC-803 cells. The MGC-803 (left side) and MKN-45 (right side) cells were treated with sEVs derived from MGC-803 cells (Con sEVs) or LSD1 knockout (KO) MGC-803 cells (KO sEVs) and stained with PKH26 for 12 h. Additionally, the cell membrane was stained with Dio, while the nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI). Scale bar = 100 µm.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "(B) Immunofluorescence confocal microscopy analysis of LSD1 (green) in LSD1 KO MGC-803 cells (left panel) and LSD1 KO MKN-45 cells (right panel) incubated with 20 μg/mL Con sEVs and KO sEVs for 12 h. The cell membrane was stained with PKH26, while the nuclei were stained with DAPI. Scale bar = 100 µm.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "(F) Expression levels of LSD1, Nanog, OCT4, SOX2, and CD44 in LSD1 KO MGC-803 cells.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "(N) Immunoprecipitation of Kme1/2 on SOX2 (WT indicates HEK293T cells co-transfected with LSD1-WT and SOX2-WT; Mut indicates HEK293T cells co-transfected with LSD1-WT and SOX2-Mut; WT, wild type; Mut, mutant).",
    "ncbi_link": "LSD1: 23028
SOX2: 6657"
  },
  {
    "caption": "(C) Expression levels of LSD1, OCT4, and SOX2 in MGC-803 and MKN-45 cells incubated with 20 μg/mL sEVs from MGC-803 or LSD1 KO MGC-803 cells for 48 h. (D) Quantification of the results of (C) (n = 3 biological replicates; mean ± SEM; *P = 0.0385 (LSD1), *P = 0.0160 (OCT4), and ***P = 0.0006 (SOX2) for MGC-803; *P = 0.0299 (LSD1), *P = 0.0147 (OCT4), and *P = 0.0258 (SOX2) for MKN-45; two-tailed unpaired Student's t-test). ",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "(B) Electrophoretic mobility shift assay (EMSA) with increasing concentration (0, 15nM, 30nM, 60nM, 1.25μM and 2.5μM) of GST-FOXD3 and fixed concentration (50nM) of 5'-Cy5 labelled dsDNA oligonucleotides (35 bp each) from Sox15 promoter (positive control), MSR, MERVL-LTR, MERVL-int, L1MdA and Hprt promoter (negative control). The experiment was repeated 3 times. (D) ChIP-qPCR enrichment of FOXD3 in mESCs using primers specific for MSR, MERVL-LTR, MERVL-int (including and excluding the FOXD3 cognate motif), L1MdA promoter sequences. Sox15 promoter and Actb promoter primers are used as positive and negative control respectively. Data is represented as percentage of input and the average of 3 biological replicates is plotted. Error bar indicates standard error of the mean (SEM). Asterisks indicate statistically significant differences compared to no antibody control levels (*: p< 0.05, paired t-test).",
    "ncbi_link": "Actb: 11461
Hprt: 15452
Sox15: 20670"
  },
  {
    "caption": "(B) Validation of select upregulated repeats in Foxd3 KO cells by RT-qPCR. The data is plotted as average fold change relative to control, after normalization to Gapdh. Error bars indicate SEM (n=3 biological replicates). Asterisks indicate statistically significant differences when compared to control (**: p<0.005, *: p<0.05, paired t-test).",
    "ncbi_link": "Foxd3: 15221
Gapdh: 14433"
  },
  {
    "caption": "(C) Immunofluorescence analysis of the MERVL-gag protein in control and Foxd3 KO cells. Nuclei are labelled with DAPI. The percentage of counted cells (~150 cells per experiment) exhibiting immunofluorescence signal is indicated. Scale bar represents 10 μm, n= 3 biological replicates.",
    "ncbi_link": "Foxd3: 15221"
  },
  {
    "caption": "(E) Immunofluorescence analysis of 2CLC markers ZSCAN4 and DPPA3 in control and Foxd3 KO cells. Nuclei are labelled with DAPI. The percentage of counted cells (~150 cells per experiment) exhibiting the immunofluorescence signal is indicated. Scale bar represents 10 μm, n=3 biological replicates.",
    "ncbi_link": "Foxd3: 15221"
  },
  {
    "caption": "(B) RT-qPCR analysis of MERVL, MSR and L1MdA in Foxd3 cKO cells, Foxd3 cKO cells over expressing full length FOXD3 or FOXD3 M1 without and with 4-OHT. Data is represented as fold change relative to respective untreated cells after normalizing to Gapdh. The average data for 3 biological replicates is plotted, error bars represent standard error mean (SEM). Asterisks indicate statistically significant differences. (**: p< 0.005, *: p<0.05 paired t-test).",
    "ncbi_link": "Foxd3: 15221
FOXD3: 15221
Gapdh: 14433"
  },
  {
    "caption": "(D) RT-qPCR analysis of, 2C genes Zscan4c and Dppa3 in Foxd3 cKO cells, Foxd3 cKO cells over expressing full length FOXD3 or FOXD3 M1 without and with 4-OHT. Data is represented as fold change relative to respective untreated cells after normalizing to Gapdh. The average data for 3 biological replicates is plotted, error bars represent standard error mean (SEM). Asterisks indicate statistically significant differences. (**: p< 0.005, *: p<0.05 paired t-test).",
    "ncbi_link": "Dppa3: 73708
Foxd3: 15221
FOXD3: 15221
Gapdh: 14433
Zscan4c: 245109"
  },
  {
    "caption": "(A) GFP immunoprecipitation analysis using GFP-SUV39H1 and GFP-SUV39H2 expressing Suv39h dn mESCs. The top panel represents immunoblot using GFP antibody and the bottom panel represents immunoblot using FOXD3 antibody. The experiment was repeated 3 times using biological replicates.",
    "ncbi_link": "Suv39h: 64707///20937"
  },
  {
    "caption": "(D) ChIP-qPCR analysis of endogenous SUV39H1 enrichment over MERVL, MSR and L1MdA in control and Foxd3 KO cells. Actb promoter is used as negative control. Data is represented as average percentage input from 3 biological replicates. Error bar indicates SEM (*: p<0.05 paired t-test).",
    "ncbi_link": "Actb: 11461
Foxd3: 15221"
  },
  {
    "caption": "(E) ChIP-qPCR analysis revealing H3K9me3 enrichment over MERVL, MSR and L1MdA in control and Foxd3 KO cells. Actb promoter is used as negative control. Data is represented as average percentage input from 3 biological replicates. Error bar indicates SEM (**: p<.005, *: p<0.05 paired t-test).",
    "ncbi_link": "Actb: 11461
Foxd3: 15221"
  },
  {
    "caption": "(G) Immunofluorescence analysis of control and Foxd3i GFP-SUV39H1 expressing Suv39h dn mESCs stained with DAPI, FOXD3 and H3K9me3. The percentage of counted cells (~150 cells per experiment) exhibiting fluorescence signal is indicated. Scale bar=2μm. n= 3 biological replicates.",
    "ncbi_link": "Foxd3: 15221
Suv39h: 20937///64707"
  },
  {
    "caption": " G EAE clinical scores of WT and IL-10-/- mice immunized s.c. with MOG + RA + IL-2, or PBS + DMSO (Veh), 7 and 21 days before induction of EAE. Results are mean + SEM (n=6 or 7). ***p <0.001, WT MOG + IL-2 + RA vs WT Veh, ##p<0.01, ###p<0.001, IL-10-/- MOG + IL-2 + RA vs IL-10-/- Veh by two-way ANOVA and Tukey post hoc test. ",
    "ncbi_link": "IL-10: 16153"
  },
  {
    "caption": "(a) Representative 2D μ-CT scans of RasV12; ctrl at day 6, RasV12; scrib-/- larvae at day 6 and day 10. Muscle (green), fat body (blue) and eye-antennal discs/tumor (red) are outlined.Scale bar: 1mm. Anterior (A), Right (R).",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(a) Quantification of tumor growth of RasV12; ctrl day 6 (n=15) RasV12; scrib-/- tumors, day 6 (n=15), day 7 (n=5), day 8 (n=4), day 9 (n=5) and day 10 (n=5).",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(b) Quantifications of muscle volume, of larvae carrying tumors of RasV12; ctrl (n=15), and RasV12; scrib-/- at day 6(n=15), day 7 (n=5), day 8 (n=5), day 9 (n=5) and dat 10 (n=5).",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(c) Quantification of width of Dorsal Oblique 3 (DO3) muscle in larvae carrying tumors of RasV12; ctrl at day 6 (n=29) and RasV12; scrib-/-at days 6 (n=29) and day 10 (n=31).",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(d) Quantification of adipose tissue volume in larvae carrying tumors of RasV12; ctrl at day 6 and RasV12; scrib-/-at days 6 and day 10.",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(e) Representative confocal images of adipose tissue in RasV12; ctrl and RasV12; scrib-/- tumors bearing animals at indicated ages. Lipid droplets are highlighted with Lipid Tox staining. Scale bar: 50μm",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(f) Quantification of dry weight of RasV12; ctrl (n=9), RasV12; scrib-/- day 6 (n=15) and day 10 (n=18) tumor bearing larvae excluding the tumor weight.",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(g) Quantification of larval motility measure by crawling distance and crawling pattern in RasV12; ctrl (n=14), RasV12; scrib-/- day 6 (n=15), day 8 (n=16) and day 10 (n=14), each colored line represents a single larva.",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(h) Coomassie feeding assay to asses food intake of RasV12; scrib-/- over time, three repeated measurements of an average food intake of 20 larvae.",
    "ncbi_link": "Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(a-e) Cartoon (top) illustrates the genotypes of the larvae, eye-antennal disc (EAD, circle: tumor cells in green and microenvironment cell in black), systemic cells are illustrated as a square (wild type cells in light brown and atg13 mutant cells in light orange) at indicated ages. Cartoon (left) illustrates the structure of cephalic complex attached to mouth hook. Representative images of Larva (image of larva using the backlight of microscope), cephalic complex (green highlights the GFP-labelled tumor clones), muscle (Phalloidin in green stains actin and Hoechst in blue stains nucleus) and adipose tissue (Lipid Tox in red stains for lipid droplets, Hoechst stains nucleus) from top to bottom. (a) RasV12; ctrl tumor bearing animal at day 6. (b) RasV12; scrib-/- tumor bearing animal at day 6. (c) RasV12; scrib-/- tumor bearing animal at day 8. (d) RasV12, scrib-/-, atg13-/-//atg13-/- at day 8. (e) RasV12, scrib-/-, atg13-/-//atg13-/- animal complemented with transgenic atg13, rescuing the tumor growth, at day 8.",
    "ncbi_link": "atg13: 40998
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(f) Quantification of area of space occupied with lobes of fat body within larval segments 4 to 8 (shown in yellow dashed line in 2a), of animals bearing tumors at day 6 RasV12; ctrl (n=45), RasV12; scrib-/- (n=30), RasV12, scrib-/-, atg13-/-//atg13-/- (n=30) and ey3.5-atg13; RasV12, scrib-/-, atg13-/-//atg13-/- (n=29) and at day 10 RasV12; scrib-/- (n=40), RasV12, scrib-/-, atg13-/-//atg13-/- (n=25) and ey3.5-atg13; RasV12, scrib-/-, atg13-/-//atg13-/- (n=28).",
    "ncbi_link": "atg13: 40998
ey3.5: 43812
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(g) Quantification of tumor volumes day 6 RasV12; ctrl (n=7), RasV12; scrib-/- (n=11) and day 8 RasV12; scrib-/- (n=13), RasV12, scrib-/-, atg13-/-//atg13-/- (n=9) and ey3.5-atg13; RasV12, scrib-/-, atg13-/-//atg13-/- (n=9).",
    "ncbi_link": "atg13: 40998
ey3.5: 43812
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(h) Quantification of Ventral Longitudinal muscle 4 (VL4) (shown in yellow dashed line in 2a) of third segment of larvae carrying at day 6 RasV12; ctrl (n=15), RasV12; scrib-/- (n=14), and at day8 RasV12; scrib-/- (n=11), RasV12, scrib-/-, atg13-/-//atg13-/- (n=12) and ey3.5-atg13; RasV12; scrib-/-, atg13-/-//atg13-/- (n=14).",
    "ncbi_link": "atg13: 40998
ey3.5: 43812
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(i) Quantification of dry weight excluding tumor of RasV12; scrib- -, atg13-/-//atg13-/-at day 6 (n=8) and day 10 (n=7).",
    "ncbi_link": "atg13: 40998
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(j) Quantification of larval motility measured by crawling distance and crawling pattern for RasV12; scrib-/-, atg13-/-//atg13-/- at day 6 (n=15) and at day 8 (n=15), each colored line represents a single larva.",
    "ncbi_link": "atg13: 40998
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(a) Changes in groups (carbohydrates, amino acids and fatty acids) of storage metabolites measured in circulating haemolymph with progressing wasting, shown as log2 changes measured by LC-MS and calculated per larvae relative to RasV12; ctrl at day 6.",
    "ncbi_link": "Ras: 43873"
  },
  {
    "caption": "(b) Volcano plot showing autophagy-dependent changes to amounts of circulating metabolites at day 6. X-axis shows the log2 of fold change of RasV12;atg13 -/-scrib-/- // atg13 -/- vs. RasV12; scrib-/- , y-axis shows -log10 p-value, calculated by t-test. Metabolite names are shown for metabolites with log2(FC) >± 1 and/or -log10(P) < 2. Green points indicate log2(FC) >± 1, blue indicate -log10(P) < 2 and red indicates for above both thresholds.",
    "ncbi_link": "atg13: 40998
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(a) The amount of glycogen in the whole larvae measured by biochemical assay (n=4), normalized to RasV12; ctrl at day 6, and per number of larvae.",
    "ncbi_link": "Ras: 43873"
  },
  {
    "caption": "(b-e) Representative confocal images of muscle and adipose tissue of larvae carrying RasV12; ctrl, RasV12; scrib-/- and RasV12; scrib-/-, atg13-/-//atg13-/- showing glycogen levels (white) at day 6 and day 8.",
    "ncbi_link": "atg13: 40998
Ras: 43873
scrib: 44448"
  },
  {
    "caption": "(A) Relative DRIP-qPCR signal values at RPL13A, APOE, MIB2 and RHOT2 genes in HeLa cells transfected with the indicated siRNAs and treated in vitro with RNase H pre-immunoprecipitation where indicated. The mean ± SEM from at least three independent experiments is shown. *p<0.05, **p<0.01, ***p<0.001 (one-tailed paired t-test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "APOE: 348
MIB2: 142678
RHOT2: 89941
RPL13A: 23521"
  },
  {
    "caption": "(A) Representative images of single-cell alkaline gel electrophoresis (comet assay) of HeLa cells transfected with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+).",
    "ncbi_link": "EGFP: 
RNH1: "
  },
  {
    "caption": "(B) Comet tail moment from single-cell alkaline gel electrophoresis (comet assay) of HeLa cells transfected with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). More than 250 total cells were considered. The mean ± SEM of the median from at least three independent experiments is shown, except for RAD1, RAD17 and UBE2B (n=2). *p<0.05, **p<0.01, ***p<0.001 (one-tailed unpaired t-test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "EGFP: 
RNH1: 
RAD1: 5810
RAD17: 5884
UBE2B: 7320"
  },
  {
    "caption": "(A) Representative images and percentage of HeLa cells with more than 5 H3S10-P foci after transfection with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). Mitotic cells were excluded for the analysis by DAPI staining. More than 300 total cells were considered. Data represent mean ± SEM from three independent experiments. *p<0.05, **p<0.01, ***p<0.001 (one-tailed paired t-test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "EGFP: 
RNH1: "
  },
  {
    "caption": "(B) Representative images and H3K9me2 nuclear signal intensity of HeLa cells transfected with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). At least three experiments were performed. The median of each population in a representative experiment with at least 100 cells per condition is shown. Boxes and whiskers indicate 25-75 and 10-90 percentiles, respectively. *p<0.05, **p<0.01, ***p<0.001 (one-tailed paired t-test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "EGFP: 
RNH1: "
  },
  {
    "caption": "(A) Fork velocity as measured by DNA combing assay in HeLa cells transfected with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). More than 200 tracks were considered except for RAD1 +RNH1 (n=125), ATR +RNH1 (n=182) and RAD18 +RNH1 (n=146). Median values are indicated. *p<0.05, **p<0.01, ***p<0.001 (Mann-Whitney U test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "EGFP: 
RNH1: 
ATR: 545
RAD1: 5810
RAD18: 56852"
  },
  {
    "caption": "(B) Fork asymmetry as measured by DNA combing assay in HeLa cells transfected with the indicated siRNAs and either pEGFP-C1 (RNH1-) or pEGFP-M27 (RNH1+). From 40 to 200 total measurements were considered for each candidate. Median values are indicated. *p<0.05, **p<0.01, ***p<0.001 (Mann-Whitney U test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "EGFP: 
RNH1: "
  },
  {
    "caption": "(A) DNA-RNA hybrids, DNA damage and fork stalling in 9-1-1/ATR/CHK1, ATM/CHK2 and PRR deficient cells. DNA-RNA hybrids represent the mean ± SEM of all the DRIP data ***p<0.001, **p<0.01, *p<0.05 (Paired t-test). DNA damage represents the mean of medians ± SEM of all the comet tail moment data ***p<0.001, **p<0.01, *p<0.05 (paired t-test). Fork stalling represents the median ± SEM of all the fork asymmetry data ***p<0.001, **p<0.01, *p<0.05 (Mann-Whitney U test). Black stars denote significant increases whereas red stars denote significant decreases.",
    "ncbi_link": "ATM: 472
ATR: 545
CHK1: 1111
CHK2: 11200"
  },
  {
    "caption": "Relative expression levels of the HIF1A-AS2 transcript in the indicated cell lines under normoxia condition were monitored by qRT-PCR analysis and represented as 39 minus Ct values.",
    "ncbi_link": "HIF1A-AS2: 100750247"
  },
  {
    "caption": "Sanger sequencing validation of RNA editing events on HIF1A-AS2. The editing frequencies of the indicated sites were quantitated based on three independent experiments and shown in Table EV 1. Asterisks mark the sites undergoing statistically significant increases in RNA editing.",
    "ncbi_link": "HIF1A-AS2: 100750247"
  },
  {
    "caption": "RNA-IP of ADAR1 in HUVECs, followed by real-time PCR analysis of the HIF-1A and HIF1A-AS2 RNAs. The relative enrichment of transcript association was normalized to the IgG. GAPDH was used as a non-binding control.",
    "ncbi_link": "GAPDH: 
HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "Cells were cultured under normal or hypoxic condition. Relative levels of the HIF1A-AS transcripts in total vs. poly(A)+ RNA fractions (F) were determined by qRT-PCR.",
    "ncbi_link": "HIF1A-AS: 100750247"
  },
  {
    "caption": "Cells were cultured under normal or hypoxic condition. Relative levels of the HIF1A-AS transcripts in subcellular fractions (G), were determined by qRT-PCR.",
    "ncbi_link": "HIF1A-AS: 100750247"
  },
  {
    "caption": "FISH analysis of the spatial distribution of HIF-1A mRNA (red) and HIF1A-AS2 transcripts (white) in HUVECs subjected to mock or CoCl2 treatment for 5 hrs. Nuclei were counterstained by DAPI. Scale bars, 10 μm.",
    "ncbi_link": "HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "Expression of HIF1A-AS2 was suppressed in HUVECs by oligo phosphodiester nucleotides (ODN)-based knockdown. Cells were then treated with CoCl2 for 5 hrs to mimic hypoxic condition, and subjected to gene expression analyses: The RNA abundance of HIF-1A and HIF1A-AS2 was analyzed by real-time PCR and normalized by 18s rRNA (A).",
    "ncbi_link": "18s rRNA: 
HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "Nuclear run-on assays were performed to assess the extent of nascent transcription of target genes in the HIF1A-AS2 knockdown cells (D).",
    "ncbi_link": "HIF1A-AS2: 100750247"
  },
  {
    "caption": "HIF-1A mRNA expression was detected in a region-specific manner (5' vs. 3') by primers corresponding to exons 1-2 (E1-2) and exon 14-15 (E14-15). To further monitor transcription activity, ChIP was performed to characterize RNA polymerase II binding on chromatin isolated from MCF7 cells under CoCl2 treatment (E), The precipitated DNA fragments were quantitatively analyzed by real-time PCR using primers for the HIF1A-AS2 and HIF-1A promoters, and normalized to the values of IgG. HIF1A-AS2 corresponds to the transcribed region.",
    "ncbi_link": "HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HIF-1A mRNA expression was detected in a region-specific manner (5' vs. 3') by primers corresponding to exons 1-2 (E1-2) and exon 14-15 (E14-15). To further monitor transcription activity, ChIP was performed to characterize RNA polymerase II binding on chromatin isolated from MCF7 cells in HIF1A-AS2-knockdown vs. control cells (F). The precipitated DNA fragments were quantitatively analyzed by real-time PCR using primers for the HIF1A-AS2 and HIF-1A promoters, and normalized to the values of IgG. HIF1A-AS2 corresponds to the transcribed region.",
    "ncbi_link": "HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. The expression levels of ADAR1, HIF-1A and HIF1A-AS2 transcripts were analyzed by qRT-PCR.",
    "ncbi_link": "ADAR1: 103
HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. Nuclear run-on assay was done to measure the newly synthesized HIF-1A and HIF1A-AS2 RNAs in ADAR1-knockdown cells, followed by real-time PCR analysis of the indicated transcripts.",
    "ncbi_link": "ADAR1: 103
HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. ChIP analysis of RNA polII binding on chromatin region of the HIF1A-AS2 and HIF-1A promoters. The extent of occupancy was compared between control and ADAR1-knockdown cells. The precipitated DNA fragments were quantitatively analyzed by real-time PCR and normalized by the values of IgG.",
    "ncbi_link": "ADAR1: 103
HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "Chromatin binding of ADAR1 to HIF1A-AS2 and HIF-1A promoters under nomoxia (20% O2) vs. hypoxia (1% O2, 5 hrs) conditions, as assessed by ChIP.",
    "ncbi_link": "HIF-1A: 3091
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. The 3'-end extension of HIF1A-AS2 RNA transcription in ADAR1 knockdown cells (GFP, control) was examined by PCR with primers corresponding to the depicted regions of HIF1A-AS2 locus. GAPDH serves as an internal control. Sequence locations are shown in kbp and relative to the transcription start site.",
    "ncbi_link": "GAPDH: 
GFP: 
ADAR1: 103
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. Expression levels of HIF-1α protein (F) by western blot",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "HUVECs were transfected with ADAR1-targeting siRNAs and subjected to hypoxia treatment for 5 hrs. Expression levels of HIF-1α downstream genes (G) by real-time PCR, as indicated. qRT-PCR results were normalized by the expression of 18s rRNA.",
    "ncbi_link": "18s rRNA: 
ADAR1: 103
HIF-1α: 3091"
  },
  {
    "caption": "Transcriptome-wide changes in the cells subjected to CoCl2 treatment, HIF1A-AS2 or ADAR1 knockdown were profiled by RNA-Sequencing. For genes that undergo up-regulation upon CoCl2 treatment (n = 505), overall expression profiles of the different cell groups are represented by the heatmap. The expression values (represented by normalized read counts) were displayed in shades of red or blue (linear scale) relative to the means of all corresponding values within individual experimental groups. Clusters of genes (based on unsupervised hierarchical clustering) are indicated and denoted by their experimental types/conditions.",
    "ncbi_link": "ADAR1: 103
HIF1A-AS2: 100750247"
  },
  {
    "caption": "GSEA comparing the gene expression profile by gene up-regulated upon CoCl2 treatment and those down-regulated in ADAR1 knockdown. The curves correspond to the observed enrichment score profiles in the CoCl2 gene set to the ADAR1 knockdown gene sets. The bar‐code plot below enrichment score plot denote the rank of each member in the CoCl2 up-regulated gene list.",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "HUVECs were transfected with the indicated combinations of siRNA (GFP as control versus ADAR1) and ODN (GFP as control versus HIF1A-AS2), followed by CoCl2 treatment for 5 hrs. The expression levels of ADAR1 and HIF-1α protein (E) were analyzed respectively by immunoblotting.",
    "ncbi_link": "GFP: 
ADAR1: 103
HIF1A-AS2: 100750247"
  },
  {
    "caption": "HUVECs were transfected with the indicated combinations of siRNA (GFP as control versus ADAR1) and ODN (GFP as control versus HIF1A-AS2), followed by CoCl2 treatment for 5 hrs. For cells in (E), RNA expression of heat shock protein-encoding genes (HSPA1A, HSPA1B, and HSPA6) with reported roles in angiogenesis were profiled by qRT-PCR.",
    "ncbi_link": "GFP: 
ADAR1: 103
HIF1A-AS2: 100750247
HSPA1A: 3303
HSPA1B: 3304
HSPA6: 3310"
  },
  {
    "caption": "Sanger sequencing validation of RNA editing of the LIMD1 (A) and VHL (B) transcripts.",
    "ncbi_link": "LIMD1: 8994
VHL: 7428"
  },
  {
    "caption": "Downregulation of ADAR1 levels in MCF7 cells was done using specific siRNAs. Cells were then subjected to hypoxia treatment for 5 hrs. The extent of knockdown and gene alterations was monitored by western blotting using antibodies targeting LIMD1, VHL, PHD1, PHD2, ADAR1 and HIF-1α, as indicated β-actin was used as loading control.",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "Translation efficiency was determined by quantifying transcript association with the polyribosome fraction, using ADAR1-depleted MCF7 cells with hypoxia treatment. The abundance of LIMD1 in polysomes was analyzed by real-time PCR and normalized by the eEF1α levels.",
    "ncbi_link": "eEF1α: 
ADAR1: 103
LIMD1: 8994"
  },
  {
    "caption": "To inspect HIF-1α protein abundance and modification with ubiquitin, anti- HIF-1α, anti-ubiquitylation (Ub), and anti-VHL immunoprecipitation experiments were performed, coupled with immunoblotting detection of ubiquitylation and HIF-1α, as indicated. MCF7 cells transfected with ADAR1 siRNA and treated with hypoxia were used. Protein signals were quantified using the ImageJ software. The fold changes of protein levels were determined on the basis of immunoreactive signals normalized by the input (In), with the control (siGFP) group being represented as 1.",
    "ncbi_link": "GFP: 
ADAR1: 103"
  },
  {
    "caption": "F: Full-length  GST-tagged wild type (wt) and RG mutant p14ARF protein, GST alone as well as GST-PRMT1 were purified from bacteria, as visualized by SDS-PAGE and Coomassie Blue staining (left and middle panel), with asterisks indicating the corresponding PRMT1 and p14ARF protein bands. GST and GST-p14ARF proteins (wt, RG) were subjected to in vitro-MT assays in the presence of GST-PRMT1 as described in (B). Methylation activities were detected subsequent to protein blotting by autoradiography (upper right panel). The asterisk highlights the methylated p14ARF wt protein, whereas the arrowhead indicates p14ARF-unrelated background signals (likely deriving from PRMT1 automethylation). Amounts of p14ARF proteins were detected by immunostaining of the autoradiographed blot using α-p14ARF antibody (lower right panel). Size markers (in kDa) are shown on the left.",
    "ncbi_link": "GST: "
  },
  {
    "caption": "A, B: HeLa  cells were transfected with empty vector (e.v., control) or Myc-tagged wild type  PRMT1-containing plasmid.  Immunofluorescence (IF) staining was performed using α-p14ARF (red, endogenous p14ARF), α-Myc (green, exogenous PRMT1) antibodies, DAPI (blue, nuclei/DNA) and Phalloidin (grey, cytoplasm/F-actin). In (A), representative IF results are shown, with asterisks indicating cells with exclusive nucleolar and arrowheads indicating cells with predominantly nucleo-/cytoplasmic p14ARF localization. The Merge displays the combination of p14ARF and PRMT1 staining. Scale bars: 15 μm. The quantification of exclusive nucleolar p14ARF was performed by cell counting (percentage of cells) and is shown for three independent experiments in (B) (mean ± SD).",
    "ncbi_link": "Myc: 
PRMT1: 3276"
  },
  {
    "caption": "C, D:  U2OS cells were transfected with EGFP-tagged p14ARF alone or in combination with Myc-tagged wild type PRMT1-containing plasmids. p14ARF-EGFP (green), DAPI (blue, nuclei/DNA) and PRMT1 (red, using α-Myc  antibody) were visualized by fluorescence microscopy, for which representative results are shown in (C), with the lower images displaying a magnification as indicated in the upper images by the rectangles. Scale bars: 10 μm. The subcellular distribution of  p14ARF-EGFP (exclusively nucleolar or not-exclusively nucleolar but predominantly nucleo-/cytoplasmic) was quantified in  p14ARF-positive and p14ARF/Myc-PRMT1-double positive cells by cell counting (percentage of cells) for three independent experiments in (D) (mean ± SD, ***: p-value ≤ 0.001 using Welch´s t-test).",
    "ncbi_link": "EGFP: 
Myc: 
PRMT1: 3276
p14: 51639"
  },
  {
    "caption": "HeLa cells were  transfected with the indicated siRNAs (two control/non-targeting siRNAs and three PRMT1-specific siRNAs). The cellular p14ARF distribution was determined by   immunofluorescence staining (IF) using α-p14ARF antibody. Representative IF images for the siControl_1 and siPRMT1_1 condition are shown in (G) (endogenous p14ARF in red and the merge additionally with DAPI in blue for nuclei/DNA). Scale bars: 15 μm.",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "A, U2OS cells were  transfected  with  EGFP-tagged wild type (wt) or mutant (RG, RF, RK) p14ARF-containing plasmids. p14ARF-EGFP (green), endogenous  NPM  as a nucleolar marker (red, using α-NPM antibody), DAPI (blue, nuclei/DNA) and Phalloidin (grey, cytoplasm/F-actin) were visualized by fluorescence microscopy, for which representative results are shown in (A). Scale bars: 10 μm.",
    "ncbi_link": "EGFP: 
p14: 51639"
  },
  {
    "caption": "D: HeLa cells were transfected with empty vector (e.v., control) or Myc-tagged wild type PRMT1-containing plasmid. Immunoprecipitation (IP) of endogenous  p14ARF or NPM was performed from cell lysates using the corresponding antibodies or IgG as negative control. IP reactions and input lysates were analyzed by immunoblotting using the indicated antibodies. Staining results of the  IP reactions derive from the same blot and exposure times with the white lines indicating where tracks were cut.",
    "ncbi_link": "Myc: 
PRMT1: 3276"
  },
  {
    "caption": "C:  HeLa cells were transfected with the indicated siRNAs (five control/non-targeting siRNAs and four  PRMT1-specific siRNAs). PRMT1 depletion and endogenous  p14ARF protein levels were analyzed by immunoblotting using α-PRMT1, α-p14ARF and α-β-TUBULIN (loading control) antibodies. The p14ARF signals were densitometrically quantified and normalized to the respective  β-TUBULIN signal, as specified by the numbers below the blot, with the siControl_2 condition set to 1.",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "PRMT1-proficient (-Dox) as well as PRMT1-depleted cells (+ Dox) were further treated with the protein synthesis inhibitor cycloheximide (CHX) and harvested after 0, 0.5, 1, 2, 3, 4, and 6 hours. Cell lysates were subjected to immunoblotting using α-p14ARF and α-β-TUBULIN (loading control) antibodies and conventional ECL detection (F). For precise quantification of the p14ARF protein stability in the -/+ Dox conditions during the CHX time course, immunoblotting was performed with independent cell lysates and primary antibodies, as in (F), which were then detected using fluorescence dye-coupled secondary antibodies and the LI-COR Odyssey system. The quantitative  p14ARF signals were normalized to the corresponding quantitative β-TUBULIN signals and displayed in (G). The CHX-untreated samples (0 hour) were set to 100% for each condition.",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "HeLa   cells were transfected with the indicated siRNAs (two control/non-targeting siRNAs and two PRMT1-specific siRNAs) and irradiated at 150 J/cm2 UVC or not irradiated. After 24 hours, the cellular distribution of endogenous p14ARF was determined by immunofluorescence (IF) staining using α-p14ARF antibody (red, endogenous p14ARF) and in the merge additionally DAPI  (blue, nuclei/DNA). Representative  IF  results are shown for two conditions (siControl_4 and siPRMT1_1) in (A), with asterisks indicating exclusively nucleolar and arrowheads indicating not-exclusively nucleolar but additionally or predominantly nucleo-/cytoplasmic p14ARF localization. Scale bars: 15 μm. The subcellular distribution of p14ARF, as determined by IF, was quantified by cell counting (percentage of cells) for all conditions (B).",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "H: CRISPR/Cas9 control (CTR_1 and CTR_2) or  PRMT1-deleted (KO_1 and KO_2) HeLa  cell lines were  irradiated at 150 J/cm2 UVC or not  irradiated. After 4 hours, immunoprecipitations (IP) of endogenous p14ARF were performed from cell lysates using α-p14ARF antibody or IgG as negative control.  IP  reactions and input lysates were analyzed by immunoblotting using the indicated antibodies. Short and long exposure times are specified.",
    "ncbi_link": "CRISPR: 
Cas9: 57852564
PRMT1: 3276"
  },
  {
    "caption": "A:  Kaplan-Meier plot was generated using the transcriptome data set of PDAC from TGCA and OncoLnc to visualize the survival of PDAC patients  with low or high PRMT1 transcript levels and short-term (<500 days, left plot) and long-term survival (>500 days, right plot).",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "A549 cells stably expressing lentivirus vector containing random shRNA or Atg7 specific shRNA were generated. (A) Cells were incubated for 2 hours in the presence or absence of 50 nM of lysosomal inhibitor chloroquine (CQ). Cell lysates were evaluated by immunoblotting. ",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "A549 cells stably expressing lentivirus vector containing random shRNA or Atg7 specific shRNA were generated. (B) Cells were infected, for 1 and 4 hours, with K. pneumonia at MOI of 10 followed by 1 hour of gentamycin treatment. Cell lysates were plated in LB agar for 18 hours and CFU were determined. Data information: the triangles and dots represent the individual test (three technical replicates per individual test) on control and Atg7 knock down cells. The bars represent the mean CFU of each group (three biological replicates each group), error bars represent standard deviation. Statistical significance between assays were calculated using two-tailed student's t test with Welch's correction. NS: not significant; *p ≤ 0.05; **p ≤ 0.01. ",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "A549 cells stably expressing lentivirus vector containing random shRNA or Atg7 specific shRNA were generated. (D-E) Cells were infected, for 1-4 hours, with WT (D) or ΔpscD P. aeruginosa (E) at MOI of 10. All infections were followed by 1 hour of gentamycin treatment. Cell lysates were plated in LB agar for 18 hours and CFU were determined. Data information: , the triangles and dots represent the individual test (three technical replicates per individual test) on control and Atg7 knock down cells. The bars represent the mean CFU of each group (three biological replicates each group), error bars represent standard deviation. Statistical significance between assays were calculated using two-tailed student's t test with Welch's correction. NS: not significant; *p ≤ 0.05; **p ≤ 0.01. ",
    "ncbi_link": "Atg7: 10533
pscD: 877924"
  },
  {
    "caption": "(B) A549 cells infected with WT or ΔpscD P. aeruginosa for 4 hours or left uninfected (NI) in the presence of lysosomal inhibitor CQ (50 nM). The cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "pscD: 877924"
  },
  {
    "caption": "(C) A549 cells stably expressing GFP-LC3 were left non-infected or infected, for 4 hours, with WT or ΔpscD P. aeruginosa, and evaluated by fluorescence microscopy. Cell nuclei were counterstained with DAPI (blue) and autophagosome were visualized as green puncta. Graph represents quantitative analysis of GFP-LC3 positive autophagosome per cell, scale bars: 10 µm. Each bar represents mean value of three independent experiments, error bars represent standard deviation. Statistical significance between assays was determined using One-way ANOVA followed by Dunn's Multiple Comparison Test. **p ≤ 0.01.",
    "ncbi_link": "GFP: 
LC3: 64862
pscD: 877924"
  },
  {
    "caption": "(D-E) A549 cells were treated for 16 hours with rapamycin 0.8 μg/ml or DMSO, then infected with either WT (D) or ΔpscD P. aeruginosa and followed by 1 hour of gentamycin treatment (E). The circles and squares represent the individual test (three technical replicates per individual test) with DMSO and rapamycin treatment. The bars represent the means of CFU from three independent experiments, error bars represent standard deviation. The significance of differences between different drug treatment was determined using two-tailed student's t test with Welch's correction. NS: not significant; *p ≤ 0.05; **p ≤ 0.01.",
    "ncbi_link": "pscD: 877924"
  },
  {
    "caption": "(C) A549 cells, stably expressing GFP-LC3, were infected with WT or P. aeruginosa mutants and evaluated by fluorescence microscopy, scale bars: 10 µm. GFP-LC3 puncta representing the autophagosomes was quantified and presented in the graph. Each bar represents mean value from three independent experiments and error bars represent standard deviation. Statistical significance between assays was determined using One-way ANOVA followed by Dunn's Multiple Comparison Test. *p ≤ 0.05; **p ≤ 0.01. P. aeruginosa mutant strains legend: ΔSTY (mutant deficient for the three cytotoxins), WT (contains all cytotoxin), ΔS (deficient for ExoS but still express ExoT and ExoY), ΔTY (express ExoS but deficient for ExoT and ExoY).",
    "ncbi_link": "GFP: 
ExoS: 879837
ExoT: 878350
ExoY: 879421
LC3: 64862"
  },
  {
    "caption": "(D,E) A549 cells, stably expressing GFP-LC3, were infected for 4 hours with WT or with one of P. aeruginosa mutants (ΔSTY, ΔS and ΔTY) and evaluated by fluorescence microscopy (D). P. aeruginosa were visualized using specific antibody (red) and the colocalized bacteria signals with GFP-LC3 puncta (green) were merged and presented as yellow. Scale bars: 10 µm. (E) Quantitative analysis of co-localization of internalized P. aeruginosa with GFP-LC3 positive puncta. The colocalization of these two signals was quantified with 10 independent visual fields of more than 100 cells. Data represent mean ± SD of three independent experiments. Statistical significance between assays was determined using One-way ANOVA followed by Dunn's Multiple Comparison Test. *p ≤ 0.05; **p ≤ 0.01.",
    "ncbi_link": "GFP: 
LC3: 64862"
  },
  {
    "caption": "(F) Representative transmission electron microscopy images of A549 cells infected with P. aeruginosa containing ExoS (ΔTY) or deficient for the three T3SS effector proteins (ΔSTY) for 4 hours. ΔSTY P. aeruginosa (white star) was engulfed by multiple membrane autophagosomes (black arrow). ΔTY P. aeruginosa (white star) were found in cytoplasm with single membrane surrounded, scale bars: 0.5 µm.",
    "ncbi_link": "ExoS: 879837"
  },
  {
    "caption": "(G) A549 cells, stably expressing lentiviral vectors containing random shRNA or Atg7 shRNA, were infected with WT or P. aeruginosa mutants (ΔSTY, ΔTY and ΔS) at MOI of 10. All infections were followed by 1 hours of gentamycin treatment. Cell lysates were plated in LB agar for 18 hours and CFU were determined. Data information: The triangles and dots represent the individual test (three technical replicates per individual test) on control and Atg7 knock down cells from three biological replicates. The bars represent the means of CFU of each group (three biological replicates each group), error bars represent standard deviation. The significance of differences between different assay was determined using two-tailed student's t test with Welch's correction, NS: not significant; **p ≤ 0.01.",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "(A) Primary airway epithelial cells were isolated from tracheas of Atg7+/+ and Atg7-/- mouse and were evaluated by immunoblotting.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(B) Sections of tracheas from Atg7+/+ and Atg7-/- mouse were evaluated by immunofluorescence microscopy following staining of nuclear DNA with DAPI (Blue), ciliated epithelial cell marker β-tubulin IV (green) and Atg7 (red). Scale bars: 20 µm.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(C,D) Atg7+/+ and Atg7-/- mice were intranasally injected with 3 x107 CFU of WT, ΔS, ΔTY or ΔSTY P. aeruginosa. After 24 hours, lungs (C), spleens and livers (D) were harvested, homogenized and diluted for CFU counting. Each data point represents bacterial count (Log10 CFU/g) from individual mouse. The horizontal lines represent the mean value from each group (6 mice each group), error bars represent standard deviation. The significance of differences between different drug treatment was determined using One-way ANOVA and Dunn's multiple comparisons test., NS: not significant; *p ≤ 0.05",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(E,F) Atg7+/+ and Atg7-/- mice were intranasally injected with PBS with or without 1 x109 CFU of ΔTY (E) ΔSTY (F). Mice survival was monitored for 10 days post infection. Kaplan-Meyer survival curves were made based on the observation of 12-18 mice/group from two independent experiments. The P-values were calculated using the log-rank test (ΔTYAtg7+/+ vs ΔTYAtg7-/-, P = 0.2186; ΔSTYAtg7+/+ vs ΔSTYAtg7-/-, P=0.0145).",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(A A549 cells were infected for 4 hours with ExoS-deficient P. aeruginosa (ΔS), ExoS containing P. aeruginosa (SWT), P. aeruginosa containing ExoS with loss-of-function mutations in the GTPase activating domain (SG-A+), in the ADP-ribosylation domain (SG+A-), or in both domains (SG-A-). Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "ExoS: 879837"
  },
  {
    "caption": "(B) A549 cells were transfected, for 24hours, with a plasmid expressing empty vector (EV), WT GFP-ExoS, a GFP-ExoS mutant for ADPRT domain (SG+A-) or a GFP-ExoS mutant deficient in both GAP and ADPRT domains (SG-A-). Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "GFP: 
ExoS: 879837"
  },
  {
    "caption": "(C) A549 cells were treated for 24 hours with 100 µM of the ADPRT activity inhibitor MIBG and then left uninfected (NI) or infected with P. aeruginosa containing ExoS with ADPRT activity only (SG-A+). Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "ExoS: 879837"
  },
  {
    "caption": "A549 cells were infected for 4 hours with WT or P. aeruginosa mutants (ΔpscD Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "pscD: 877924"
  },
  {
    "caption": "F) A549 cells were infected for 4 hours with ExoS-deficient P. aeruginosa (ΔS), ExoS containing P. aeruginosa (SWT), P. aeruginosa containing ExoS with loss-of-function mutations in the GTPase activating domain (SG-A+), in the ADP-ribosylation domain (SG+A-), or in both domains (SG-A-). Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "ExoS: 879837"
  },
  {
    "caption": "(A) A549 cells were transfected with empty vector (VE) and vector contains Ras-G12V for 24 hours, followed by a 4-hours infection with P. aeruginosa ΔSTY or ΔTY. Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "Ras: "
  },
  {
    "caption": "(B) A549 cells were transfected, for 24 hours, with empty vector (VE) and vectors contain Ras-G12V or Ras-G12V&R41K followed by a 4-hours infection with P. aeruginosa ΔSTY or ΔTY. Cell lysates were evaluated by immunoblotting.",
    "ncbi_link": "Ras: "
  },
  {
    "caption": "(A) A549 cells were transfected, for 48 hours, with a mCherry-DFCP1 plasmid and then infected, for 4 hours, with P. aeruginosa (WT, ΔSTY, ΔS, ΔTY, SG-A-, SG-A+ or SG+A-) and the mCherry puncta number per cell was analyzed by fluorescence microscopy. Representative immunofluorescence images were showed, and scale bars represent 10 µm. (B) Quantitative analysis of mCherry-DFCP1 puncta by visually count more than 100 cells for each sample. Each bar represents mean value of from three independent experiments and error bars represent standard deviation. The significance of differences between assays was determined using ANOVA with Dunnett multiple-comparison posttest, NS: not significant; *p ≤ 0.05; **p ≤ 0.01. ",
    "ncbi_link": "mCherry: 
DFCP1: 53349"
  },
  {
    "caption": "(A A549 cells, transfected for 48 hours with vector encoding Flag-Atg14L, were infected with P. aeruginosa (WT, ΔSTY, ΔS, ΔTY Flag-Atg14L-Vps34 complex was immunoprecipitated (IP) by Flag-antibody magnetic beads and evaluated by immunoblotting.",
    "ncbi_link": "Flag: 
Atg14L: 22863"
  },
  {
    "caption": "C) A549 cells, transfected for 48 hours with vector encoding Flag-Atg14L, were infected with P. aeruginosa , ΔSTY SG-A-, SG-A+ or SG+A-). Flag-Atg14L-Vps34 complex was immunoprecipitated (IP) by Flag-antibody magnetic beads and evaluated by immunoblotting.",
    "ncbi_link": "Flag: 
Atg14L: 22863"
  },
  {
    "caption": "(A) Amylose pulldown from  benzonase-treated HEK293T cell lysates expressing 2xMBP-BRCA2NT in untreated or irradiated   cells (6Gy; +IR). DDX5 and BRCA2NT (MBP) detected by immunoblot. StainFree  images of the gels before transfer were used as loading control",
    "ncbi_link": "MBP: 
BRCA2: 675"
  },
  {
    "caption": "(C) Left: Representative  images of in situ proximity ligation assay (PLA) between BRCA2  and  DDX5  antibodies in  U2OS cells either left untreated (-) or irradiated (4h post-IR; 6 Gy). Nuclei as defined by auto threshold plugin on the DAPI image (Image J) our outlined in yellow. When indicated, cells were transfected with a plasmid expressing RNase H1 (RH) 24h before or treated with  Cordycepin (Cordy) for 2h at 37°C before fixation. Single antibody controls from untreated siC cells are shown. Scale bar indicates 10 µm. Right: Quantification of the  number of PLA  spots per nucleus. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA spot.",
    "ncbi_link": "RH: 
RNase H1: "
  },
  {
    "caption": "(D) Diagram showing the BRCA2 N-terminal truncations used in this study and amylose pulldown from HEK293T whole cells extracts overexpressing the indicated BRCA2 N-terminal truncations (BRCA2T1, BRCA2LT2, BRCA2LT3) or the 2xMBP tag. DDX5 and BRCA2 truncations were detected using specific antibodies against DDX5 and MBP, respectively. StainFree images of the gels before transfer were used as loading control",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "(A) Left: Representative  images  of S9.6  immunofluorescence of U2OS cells depleted of BRCA2 (siBRCA2),  DDX5  (siDDX5) or control cells (siC) after transfection with either an empty plasmid or a plasmid expressing  DDX5. The merged  images show the signal of S9.6, nucleolin (nucleoli) antibodies and DAPI staining. Scale bar indicates 25 µm. Right: Quantification of S9.6 average nuclear intensity of U2OS cells depleted of  BRCA2 (siBRCA2), DDX5  (siDDX5) or control cells (siC) after transfection with either an empty plasmid or a plasmid expressing DDX5. The red line in the plot indicates the median and each symbol represents the value of a single cell. The statistical significance of the difference was calculated with Mann-Whitney U-test and the p-values show the significant difference. The data represent at least 235 cells per condition from three independent experiments.",
    "ncbi_link": "BRCA2: 675
DDX5: 1655"
  },
  {
    "caption": "(B) Top: Representative  images of in situ PLA performed with anti-DDX5 and S9.6 antibodies in EdU-labelled U2OS  cells. Where indicated, cells were transfected with a plasmid expressing RNase H1 (RH). Nuclei as defined by auto threshold plugin on the  DAPI image  (Image J) our outlined in yellow. Bottom: Quantification of  PLA spots per nucleus  in each condition as indicated. At least 300 cells per condition were counted from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test, the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single  PLA  spot.",
    "ncbi_link": "RH: 
RNase H1: "
  },
  {
    "caption": "(C) Representative screenshot of a specific genomic region showing DRIPc-seq  profiles at Watson (W) and Crick (C) strands in K562  cells depleted of DDX5 (siDDX5) or control cells (siC) from two independent experiments.",
    "ncbi_link": "DDX5: 1655"
  },
  {
    "caption": "(D) DNA-RNA hybrid distribution along protein-coding genes containing DRIPc-seq peaks in both conditions (siC and siDDX5) and replicates. Gene metaplots represent the mean of antisense or sense mean DRIPc-seq signal from two independent experiments in K562  cells depleted of DDX5 (siDDX5) or control cells (siC) as indicated.",
    "ncbi_link": "DDX5: 1655"
  },
  {
    "caption": "(A) Left: Representative images of in situ PLA  between S9.6 and γH2AX antibodies in  U2OS  cells depleted of BRCA2 (siBRCA2), DDX5 (siDDX5) or control cells (siC). When indicated, cells were transfected with a plasmid expressing RNase H1 (RH) 24h before or treated with Cordycepin  (Cordy) for 2h at 37°C before fixation. Single antibody controls from non-irradiated siC cells are shown. Scale bar indicates 10 µm. Nuclei  as defined by auto threshold plugin on the  DAPI image (Image J) our outlined in yellow. Right: Quantification of PLA  spots per nucleus in each condition as indicated. At least 500 cells per condition were counted from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single  PLA spot.",
    "ncbi_link": "RH: 
RNase H1: 
BRCA2: 675
DDX5: 1655"
  },
  {
    "caption": "(B) DRIP-qPCR signal values at RBMXL1 and HIST1H2BG loci in U2OS  DIvA cells transfected with the indicated siRNAs and treated in vitro with RNase H1  (RH) pre-immunoprecipitation where indicated. The experiment was performed in both untreated cells (-OHT) and after tamoxifen addition (+OHT). The data represent the mean ± SEM from at least four independent experiments. The statistical significance of the difference was calculated with unpaired one-tail t-test and the p-values show the significant difference.",
    "ncbi_link": "RH: 
RNase H1: 
HIST1H2BG: 8347
RBMXL1: 494115"
  },
  {
    "caption": "(A) Top: Scheme showing the experimental set up for laser  irradiation in DDX5-GFP  transfected  U2OS cells depleted of BRCA2 (siBRCA2) or control cells (siC). Middle: Live cell imaging of the recruitment of  GFP-53BP1 or  DDX5-GFP to DNA  damage tracks at different time points as indicated. Exposure and processing were adjusted to best demonstrate stripes and anti-stripes. Scale bar indicates 10 µm. Bottom left: Western blot showing the siRNA mediated knock-down of BRCA2 from U2OS cells transfected with DDX5-GFP. Bottom right: Quantification of the percentage of transfected cells that exhibit  DDX5-GFP \"anti-stripe\" pattern (reduced GFP signal at  DNA  damage tracks compared to the signal in the nucleus) at the times indicated in cells depleted of BRCA2 (siBRCA2) or treated with control siRNA (siC). The data represent the mean ± SEM from three independent experiments.",
    "ncbi_link": "GFP: 
BRCA2: 675
DDX5: 1655"
  },
  {
    "caption": "(B) DDX5 ChIP-qPCR signal values at  RBMXL1 and ASXL1 loci in U2OS DIvA cells transfected with the indicated siRNAs and either untreated cells (-OHT) or after tamoxifen addition (+OHT). The data represent the mean ± SEM from three independent experiments. The green line represents the background levels of DDX5 signal. The statistical significance of the difference was calculated with unpaired one-tail t-test and the p-values show the significant differences between untreated cells (-OHT) and after tamoxifen addition (+OHT).",
    "ncbi_link": "ASXL1: 171023
RBMXL1: 494115"
  },
  {
    "caption": "(C) Top: Representative images of immunofluorescence  of U2OS DIvA cells depleted of BRCA2 (siBRCA2), DDX5 (siDDX5) or control cells (siC) and either untreated cells (-OHT) or after tamoxifen addition (+OHT), as indicated. Scale bar indicates 10 µm. Bottom: Quantification of the number of γH2AX foci per nucleus  (left) and DDX5 nuclear intensity (right). The data represent at least 800 cells per condition from three independent experiments. The red line in the plot indicates the median and each symbol represents the value of a single cell. The statistical significance of the difference was calculated with Mann-Whitney U-test and the p-values show the significant difference.",
    "ncbi_link": "BRCA2: 675
DDX5: 1655"
  },
  {
    "caption": "(A) Left: GFP pull-down assay from whole cells extracts of  BRCA2 deficient DLD1 expressing BRCA2 (WT) or the variant T207A (T207A). DLD1 BRCA2+/+ (+/+) cell extracts were used as control for the GFP-trap. DDX5 and BRCA2 were detected with specific antibodies against DDX5 and BRCA2, respectively. StainFree images of the gels before transfer was used as loading control (cropped image is shown). Right: Quantification of the GFP-trap pull-down experiments calculated as the co-immunoprecipitated DDX5 with either BRCA2 WT or BRCA2-T207A relative to the input levels of DDX5  and the amount of  immunoprecipitated EGFPMBP-BRCA2. Results are presented as the fold change compared to the BRCA2 WT clone. The data represents the mean ± SD of three independent experiments. Statistical significance of the difference was calculated with unpaired t test and the p-values show the significant difference.",
    "ncbi_link": "GFP: 
BRCA2: 675"
  },
  {
    "caption": "(B) Left: Representative  images  of S9.6  immunofluorescence  of DLD1 cells bearing BRCA2 (WT) or BRCA2-T207A (T207A). The merged images show the signal of S9.6, nucleolin (nucleoli) antibodies and DAPI staining. Scale bar indicates 25 µm. Right: Quantification of the average nuclear intensity of S9.6 antibody in  DLD1 BRCA2-WT (WT) or BRCA2-T207A (T207A) cells transfected with either a plasmid expressing GFP alone (-RH) or GFP-RNase H1 (+RH), as indicated. The red line in the plot indicates the median and each symbol represents the value of a single cell. Data correspond to at least 170 cells per condition from two independent experiments. The statistical significance of the difference was calculated with Mann-Whitney U-test; p-values show the significant difference.",
    "ncbi_link": "GFP: 
RH: 
RNase H1: 
BRCA2: 675"
  },
  {
    "caption": "(C) Relative DRIP-qPCR signal values (respect to the siC level at each locus) at the MALAT1, RRPH1 and HIST1H2BG loci in DLD1 BRCA2-/- cells bearing BRCA2 (WT) or  BRCA2-T207A (T207A) and treated in vitro with RNase H1 (RH) pre-immunoprecipitation  where indicated. The data represent the mean ± SEM from seven independent experiments. The statistical significance of the difference was calculated with paired t-Student test; the p-values show the significant difference.",
    "ncbi_link": "RH: 
RNase H1: 
RRPH1: 
BRCA2: 675
HIST1H2BG: 8347
MALAT1: 378938"
  },
  {
    "caption": "(D) Top: Representative images of In situ PLA performed between BRCA2 and DDX5  antibodies in cells bearing BRCA2 (WT) or BRCA2-T207A (T207A), as indicated. Cells were fixed directly or 4h post-irradiation  (6Gy). Single antibody controls in non-irradiated BRCA2 WT cells are shown. Scale bar indicates 10 µm. Bottom: Quantification of the number of PLA spots per nucleus. At least 750 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA spot.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "(A) Top: Representative images  of In situ PLA performed between  DDX5 and S9.6 (DNA-RNA hybrids) antibodies in BRCA2 deficient  DLD1 cells (BRCA2-/-) or DLD1  stable clones expressing  BRCA2 (WT) or BRCA2-T207A (T207A). Cells were fixed directly or 4h post-irradiation (6Gy). When indicated, cells were transfected/treated with RNase H1 (RH) prior to fixation. Single antibody controls in non-irradiated BRCA2 WT cells are shown. Scale bar indicates 10 µm. Bottom: Quantification of the number of PLA spots per nucleus. At least 500 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA spot. (B) Top: Representative images of In situ PLA performed between DDX5 and γH2AX antibodies in BRCA2 deficient DLD1 cells (BRCA2-/-) bearing BRCA2 (WT) or BRCA2-T207A (T207A). Cells were fixed directly or 4h post-irradiation (6Gy). When indicated, cells were transfected/treated with RNase H1 (RH) prior to fixation. Single antibody controls in non-irradiated BRCA2 WT cells are shown. Scale bar indicates 10 µm. Bottom: Quantification of the number of PLA  spots per nucleus. At least 600 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA spot. ",
    "ncbi_link": "RH: 
RNase H1: 
BRCA2: 675"
  },
  {
    "caption": "(C) Left: Representative  images  of the recruitment of transient transfected  GFP-MBP-BRCA2  (WT and T207A) to DNA damage tracks at 5 min post-irradiation in U2OS cells. γH2AX is used as a marker of  DNA  damage. Scale bar indicates 10 µm. Right: Quantification of the  intensity of GFP signal at the laser tracks. At least 130 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the two samples we applied an unpaired t-test. The red line in the plot indicates the median and each symbol represents a single cell intensity  value.",
    "ncbi_link": "GFP: 
MBP: 
BRCA2: 675"
  },
  {
    "caption": "(D) Top: Representative images of in situ PLA performed between S9.6 (DNA-RNA hybrids) and anti-γH2AX antibodies in BRCA2 deficient DLD1 cells (BRCA2-/-) bearing BRCA2  (WT) or BRCA2-T207A (T207A). When indicated, cells were transfected/treated with RNase H1 (RH) or treated with Cordycepin (Cordy) for 2h at 37°C before fixation. Single antibody controls in non-irradiated BRCA2  WT cells are shown. Scale bar indicates 10 µm. Nuclei  as defined by auto threshold plugin on the  DAPI image (Image J) our outlined in yellow. Bottom: Quantification of the number of PLA spots per nucleus. At least 600 cells were counted per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single PLA  spot.",
    "ncbi_link": "RH: 
RNase H1: 
BRCA2: 675"
  },
  {
    "caption": "(A) Top: Representative  immunofluorescence images of cells stained for RAD51 (green) in U2OS cells depleted of  DDX5 (siDDX5) and in control cells (siC) in non-treated (-) or different time points  after exposure to  IR (6Gy), as indicated. Scale bar indicates 10 µm. Bottom: Graph showing the average number of  RAD51 repair foci in both cell lines. The data represent the mean ± SEM of three independent experiments.",
    "ncbi_link": "DDX5: 1655"
  },
  {
    "caption": "(B) Top: Representative immunofluorescence images of DLD1 BRCA2  deficient cells (BRCA2-/-) or BRCA2-/- cells expressing BRCA2 WT (WT) or BRCA2-T207A (T207A) in non-treated or at different  time points post-IR (6 Gy), as indicated; hybridized with anti-RAD51 antibody (green). Scale bar indicates 10 µm. Bottom: Graph showing the average  number  of RAD51 repair foci in the three cell lines. The data represent the mean ± SEM of three independent experiments.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "(C) Left: Representative  immunofluorescence images of DLD1 BRCA2 WT or BRCA2-T207A cells 4h post-irradiation (6Gy) hybridized with anti-γH2AX and anti-RPA antibodies. Right: Quantification of the  number  of γH2AX and RPA foci per  nucleus, as indicated. The data represent at least 400 cells per condition from two independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single focus.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "(D) Left: Representative  immunofluorescence images of DLD1 BRCA2-T207A cells 2h post-irradiation (6Gy), as indicated, hybridized with anti-γH2AX and anti-RAD51  antibodies. (RH)  RNase H. Right: Quantification of the number  of  γH2AX foci (left) or  RAD51 foci (right) per nucleus. When indicated, cells were transfected with a plasmid expressing RNase H1 (RH) 48h prior fixation. The data shown is from at least 400 cells per condition from three independent experiments. For statistical comparison of the differences between the samples we applied a Kruskal-Wallis test followed by Dunn's multiple comparison test and the p-values show significant differences. The red line in the plot indicates the median and each symbol represents a single focus.",
    "ncbi_link": "RH: 
RNase H: 
RNase H1: 
BRCA2: 675"
  },
  {
    "caption": "(E) Top: Subcellular fractionation showing amount of  RAD51 in DLD1  stable clones expressing BRCA2-T207A (T207A) in chromatin  fraction. When indicated, cells were irradiated  (2h treatment) and/or transfected with a plasmid expressing  RNase H1 (RH) 48h prior fixation. α-tubulin  and Histone H3 signals are shown as markers of cytoplasmic and chromatin fraction respectively. Bottom: quantification of  RAD51 levels detected by Western blot  with a RAD51 specific antibody in chromatin fraction relative to  RAD51 levels in WCE. Results are presented as the fold change compared to the untreated sample. The data represents the mean ± SD of three independent experiments. Statistical significance of the difference was calculated with unpaired t test and the p-values show the significant difference.",
    "ncbi_link": "RH: 
RNase H1: "
  },
  {
    "caption": "(A) STK38 interacts with XPO1. HekRasV12 cells were transiently transfected with myc-STK38(wt) together with either Flag-XPO1(wt) plasmid, Flag-control (ctrl = Sirt3) plasmid or without DNA. 24h later, cells were incubated with Okadaic Acid (OA), (final concentration = 1µM) for 1 hour or with DMSO. Flag fusions were pulled-down and co-immunoprecipited proteins were analyzed by western blotting (WB). Upper panel displays whole cell lysates (WCL) and lower panel represents immunoprecipitated proteins.",
    "ncbi_link": "Flag: 
myc: 
Sirt3: 23410
STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "STK38 accumulates in the cytoplasm upon nutrient starvation in a XPO1-dependant manner. (B) HeLa cells were transfected with myc-STK38(wt) plasmid. The next day, cells were incubated with DMEM or EBSS in the presence of XPO1 inhibitors KPT-185 or KPT-330 as indicated (final concentration = 1 µM) or DMSO for 4 hours. Cells were then fixed and stained for myc-tag. Representative images are shown and scale bars are 40 µm.",
    "ncbi_link": "myc: 
STK38: 11329"
  },
  {
    "caption": "STK38 accumulates in the cytoplasm upon nutrient starvation in a XPO1-dependant manner. (C) Quantification of myc-STK38(wt) nuclear/cytoplasmic staining (n > 30 cells from 3 independent experiments, mean ± SEM; *p<0.05, **p<0.01, ***p<0.001, Mann-Whitney test).",
    "ncbi_link": "myc: 
STK38: 11329"
  },
  {
    "caption": "XPO1 activity is required for nutrient starvation-induced autophagy. (E) HeLa cells stably expressing the GFP-LC3-RFP-LC3ΔG reporter autophagic probe [26] were incubated with DMEM or EBSS in the presence of XPO1 inhibitors KPT-185 or KPT-330 (final concentration = 1 µM) or DMSO for 4 hours. The GFP-LC3 (degraded upon autophagy) and RFP-LC3ΔG (non-degraded upon autophagy) signals were recorded by FACS analysis and then shown as a ratio recapitulating overall LC3 level (n=3 independent experiments, mean ± SEM; *p<0.05, **p<0.01, ns, not significant, Mann-Whitney test). Here again, incubation with XPO1 inhibitors significantly impaired the autophagy process",
    "ncbi_link": "GFP: 
RFP: 
LC3: 81631"
  },
  {
    "caption": "STK38 kinase activity is required and sufficient for its cytoplasmic accumulation upon nutrient starvation. (A) HeLa cells silenced for endogenous STK38 were transfected with myc-STK38(wt) expressing plasmid, myc-STK38(K118R) (STK38 kinase-dead version) plasmid or with HA-STK38(PIF) (STK38 constitutively active version) plasmid. 24 hours later, cells were incubated with DMEM or EBSS for 4 hours, fixed and stained for myc-tag or HA-tag. Representative images are shown and scale bars are 40 µm.",
    "ncbi_link": "HA: 
myc: 
STK38: 11329"
  },
  {
    "caption": "STK38 kinase activity is required and sufficient for its cytoplasmic accumulation upon nutrient starvation. (B) Graphical representation of tag-STK38 variants nuclear staining/cytoplasmic staining (n > 30 cells from 3 independent experiments, mean ± SEM; **p<0.01, ***p<0.001, ns, not significant, Mann-Whitney test).",
    "ncbi_link": "STK38: 11329"
  },
  {
    "caption": "STK38 kinase activity is required and sufficient for nutrient-starvation induced autophagy. (C) HeLa cells stably expressing the GFP-LC3-RFP-LC3ΔG autophagic probe [26] were transiently transfected with siRNA targeting the 3'UTR region of endogenous STK38 (or with non-targeting siRNA (siNT)). The next day, cells were transiently transfected with the indicated STK38 mutants expressing plasmids 24 hours after plasmid transfection, cells were incubated with DMEM or EBSS for 4 hours. The GFP-LC3 (degraded upon autophagy) and RFP-LC3ΔG (non-degraded upon autophagy) signals were recorded by FACS analysis and then shown as a ratio recapitulating overall LC3 level (n=4 independent experiments, mean ± SEM; *p<0.05, ***p<0.001, ns, not significant, Mann-Whitney test). depleting STK38 prevents autophagy to take place. This effect was partially reversed by expressing the wt ORF as well as constitutively active STK38 whereas kinase-dead version failed to reproduce endogenous STK38 effect. Expression of constitutively active STK38 is sufficient to induce a substantial change in the autophagic flux upon nutrient rich conditions",
    "ncbi_link": "GFP: 
RFP: 
LC3: 81631
STK38: 11329"
  },
  {
    "caption": "STK38 kinase activity is required and sufficient for nutrient-starvation induced autophagy. (D) HeLa cells were transiently transfected with siRNA targeting the 3'UTR region of endogenous STK38 (or with non-targeting siRNA (siNT)) and then transiently transfected with the indicated STK38 mutants expressing plasmids 48h after. The next day, the cells were incubated with DMEM or EBSS for 4 hours and overall p62 level was quantified for autophagy estimation (n = 3 independent experiments, mean ± SEM; ***p<0.001, ns, not significant, Student's t test).",
    "ncbi_link": "STK38: 11329"
  },
  {
    "caption": "(A-B) STK38 is required for XPO1_S1055 phosphorylation. (A) HeLa cells were transiently transfected with the indicated siRNA and subjected to Flag-XPO1(wt) transient transfection the following day. 48 hours later, cells were incubated with Okadaic Acid (OA, final concentration = 1 µM) for 1 hour or with DMSO. Immunoblotting was performed on whole cell lysates with indicated antibodies. (B) Graphical representation of the phospho S1055-XPO1 signal on total XPO1 (n = 3 independent experiments, mean ± SEM; *p<0.05, ns, not significant, Mann-Whitney test). As expected, XPO1 is phosphorylated on its Ser1055 upon OA treatment but not when STK38 is silenced",
    "ncbi_link": "Flag: 
STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "(C) STK38 kinase activity is required for XPO1_S1055 phosphorylation. HekRasV12 cells silenced (or not) for endogenous STK38 were transfected with Flag-XPO1(wt) expression plasmid in addition to myc-STK38(wt) or myc-STK38(K118R) (STK38 kinase-dead version) plasmids. The next day, cells were treated with 1 µM OA or with vehicle (DMSO) for 1 hour. Flag fusions were immunoprecipited and pulled-down proteins were analyzed by western blotting. Upper panel displays immunoprecipited proteins and lower panel represents whole cell lysates.",
    "ncbi_link": "Flag: 
myc: 
STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "(A) Graphical representation of XPO1 protein. C528 to S amino acid mutation confers XPO1 resistance to both KPT-185 and KPT-330 chemical inhibitors [24]. S1055 amino acid correspond to the phosphorylation target of the STK38. Finally, the ΔCter region is also highlighted corresponding to a XPO1 construct lacking the 39 C-terminal residues (B-C) XPO1_S1055 phosphorylation is required and sufficient for STK38 nuclear exit upon nutrient starvation. (B) HeLa cells were transiently transfected with myc-STK38(wt) in addition to indicated Flag-XPO1 mutant plasmids. 24 hours later, cells were incubated with DMEM or EBSS for 4 hours both supplemented with KPT-185 (final concentration = 1 µM) in order to inhibit endogenous XPO1 activity. Cells were then fixed and stained for Flag and myc tags. Only cells positives for both Flag-XPO1 and myc-STK38(wt) were captured. Representative images are shown and scale bars are 40 µm. (C) Graphical representation of myc-STK38(wt) nuclear staining/cytoplasmic staining (n > 30 cells from 3 independent experiments, mean ± SEM; ***p<0.001, ns, not significant, Mann-Whitney test). Expression of wt XPO1 failed to induce cytoplasmic localization of STK38 upon nutrient starvation in presence of KPT-185 where C528S mutant recapitulates results described in Figure 2B-C. Expression of phosphonegative XPO1 (S1055A) failed to induces STK38 cytoplasmic localization upon EBSS treatment while phosphomimetics XPO1 (S1055D and S1055E) were sufficient to promote STK38 cytoplasmic localization without autophagic stimuli. Finally, expression of XPO1 lacking in its 39 C-terminal residues mimicked phosphomimetics variants.",
    "ncbi_link": "Flag: 
myc: 
STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "(D) HAP1 cells carrying genomic XPO1 mutations of S1055 were subjected for IMDM (nutrient rich medium) or EBSS (starvation) incubation for 4 hours followed by western-blot analysis for p62 level measurement. This result indicates that p62 degradation in starvation conditions was inhibited in XPO1_S1055A HAP1 cells whereas p62 degradation was potentiated in both phosphomimetics variant (S1055D & S1055E) (n = 4 independent experiments, mean ± SEM; *p<0.05, ns, not significant, Mann-Whitney test",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "(E) Hek-HT-iRFP-LC3 cells were transiently transfected with siRNA targeting endogenous STK38 (or with non-targeting siRNA (siNT)). Two days after, cells were transiently transfected with indicated Flag-XPO1 mutant plasmids. 24 hours later, cells were incubated with DMEM or EBSS for 4 hours both supplemented with KPT-185 (final concentration = 1 µM) in order to inhibit endogenous XPO1 activity and with chloroquine (final concentration = 10 µM). Cells were then fixed and the number of iRFP-LC3 dots per cell was recorded only in cells positive for Flag-XPO1 mutants As expected, silencing of endogenous STK38 prevented the formation of LC3 dots upon starvation where introduction of phosphonegative XPO1 (S1055A) failed also to increase LC3 dots upon starvation. Interestingly, phosphomimetic XPO1 (S1055D) was sufficient to increase the number of LC3 dots even in complete and also STK38-depleted conditions.",
    "ncbi_link": "Flag: 
iRFP: 
LC3: 81631
STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "(A) XPO1 and STK38 are required for Beclin1 cytoplasmic accumulation upon nutrient starvation-induced autophagy. HeLa cells were transiently transfected with the indicated siRNA (control and KPT conditions = siNT). 72 hours later, cells were incubated with XPO1 inhibitors KPT-185 or KPT-330 as indicated (final concentration = 1 µM) or with DMSO for all other conditions for 2 hours prior incubation with DMEM or EBSS supplemented (or not) with inhibitors for 2 hours. Cells were fixed and stained for endogenous Beclin1. Graphical representation of endogenous Beclin1 nuclear staining/cytoplasmic staining (n > 30 cells from 3 independent experiments, mean ± SEM; *p<0.05, ***p<0.001, ns, not significant, Mann-Whitney test). XPO1 activity inhibition by both KPT-185 and KPT-330 as well as STK38 silencing failed to induce Beclin1 cytoplasmic accumulation upon nutrient starvation",
    "ncbi_link": "STK38: 11329"
  },
  {
    "caption": "(B) XPO1_S1055 phosphorylation is required and sufficient for Beclin1 nuclear exit upon nutrient starvation. Genome edited XPO1 mutant HAP1 cells were incubated with IMDM (complete) or EBSS (starvation) for 2 hours. Cells were then fixed and stained for endogenous Beclin1. Graphical representation of endogenous Beclin1 nuclear staining/cytoplasmic staining (n > 30 cells from 3 independent experiments, mean ± SEM; ***p<0.001, ns, not significant, Mann-Whitney test). Here, phosphonegative XPO1 failed to induce Beclin1 cytoplasmic accumulation upon nutrient starvation whereas phosphomimetics variant (S1055D & S1055E) potentiated Beclin1 cytoplasmic accumulation",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "(C) Genome edited XPO1 mutant HAP1 cells were transiently transfected with siRNA targeting endogenous STK38 (siSTK38#206 or with non-targeting siRNA (siNT)). 72 hours later, cells were incubated with IMDM (complete) or EBSS (starvation) for 2 hours. Cells were then fixed and stained for endogenous Beclin1. Graphical representation of endogenous Beclin1 nuclear staining/cytoplasmic staining (n = 30 cells from 2 independent experiments). Here, phosphomimetic XPO1 (S1055D) potentiated Beclin1 cytoplasmic localization in both complete and starvation condition even in the absence of STK38 as compared to cells carrying wt XPO1",
    "ncbi_link": "STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "(A) XPO1 and STK38 are required for YAP1 nuclear export at high confluence. A549 cells were transiently transfected with the indicated siRNA (control and KPT conditions = siNT) at low or high confluency. 48 hours later, cells were incubated overnight in the presence of XPO1 inhibitors KPT-185 and KPT-330 (final concentration = 1 µM) or with DMSO for all other conditions. The next day, cells were fixed and stained for endogenous YAP1. Quantitative representation of YAP1 nuclear fluorescence intensity (n > 300 cells from 3 independent experiments, mean ± SEM; ***p<0.001, Mann-Whitney test). XPO1 activity inhibition by both KPT-185 and KPT-330 as well as STK38 silencing failed to induce YAP1 nuclear exit at high confluence",
    "ncbi_link": "STK38: 11329"
  },
  {
    "caption": "(B) XPO1_S1055 phosphorylation is required and sufficient for YAP nuclear exit. Genome edited XPO1 HAP1 cells were cultured for two days at low versus high confluency. Cells were then fixed and stained for endogenous YAP1. Quantitative representation of YAP1 nuclear fluorescence intensity (n > 300 cells from 3 independent experiments, mean ± SEM; ***p<0.001, Mann-Whitney test). Here, phosphonegative XPO1 failed to induce YAP nuclear exit at high confluence whereas phosphomimetics variant (S1055D & S1055E) potentiated YAP1 nuclear exit",
    "ncbi_link": "XPO1: 7514"
  },
  {
    "caption": "(C) Genome edited XPO1 mutant HAP1 cells were transiently transfected with siRNA targeting endogenous STK38 (siSTK38#206 or with non-targeting siRNA (siNT)) at low or high confluence. 72 hours later, cells were fixed and stained for endogenous YAP1. Quantitative representation of YAP1 nuclear fluorescence intensity (n = 150 cells from 2 independent experiments). Here, phosphomimetic XPO1 (S1055D) potentiated YAP1 nuclear exit at both low and high confluences even in the absence of STK38 as compared to cells carrying wt XPO1",
    "ncbi_link": "STK38: 11329
XPO1: 7514"
  },
  {
    "caption": "C Top: Schematic illustration of the miR-17-92 cluster with colours marking miRNAs belonging to the same miRNA family. Bottom: TaqMan analysis of the mature miR-17-92 miRNAs in Srsf3 knockout (KO) and control (Ctrl) iPSCs (*P<0.05, ***P<0.001, two-tailed unpaired Student's t-test, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "miR-17: 723905
Srsf3: 20383"
  },
  {
    "caption": "B TaqMan analysis of the six miR-17-92 miRNAs in HEK293T cells overexpressing the WT-miR-17-92, 17/20a-∆CNNC or total-∆CNNC construct (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, One-way ANOVA, mean as ± SEM, n=4, biological replicates).",
    "ncbi_link": "miR-17: 
miR-17: 407975"
  },
  {
    "caption": "C Western blot analysis of HA-tagged SRSF3-FL or SRSF3-∆RS expression in LIM1215 cells (detection with a HA-antibody).",
    "ncbi_link": "HA: 
SRSF3: 6428"
  },
  {
    "caption": "D TaqMan analysis of the six miR-17-92 miRNAs in LIM1215 cells overexpressing empty pCGN vector, SRSF3-FL or SRSF3-∆RS constructs (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, One-way ANOVA, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "miR-17: 407975
SRSF3: 6428"
  },
  {
    "caption": "B Visualization and comparison of WT miR-17-92 SHAPE reactivities in control and SRSF3-KD cells. First panel: Mean control (blue) and SRSF3-KD (red) SHAPE reactivities, calculated over 11nt sliding windows. Second panel: ∆SHAPE reactivity differences between control and SRSF3-KD. Regions with higher reactivity in control are marked with blue shading and regions with higher reactivity in SRSF3-KD with red shading. Third panel: The SRSF3-KD to control reactivity ratios. The black boxes mark the CNNC sites.",
    "ncbi_link": "miR-17: 407975
SRSF3: 6428"
  },
  {
    "caption": "G Visualization and comparison of total-∆CNNC miR-17-92 SHAPE reactivities in control and SRSF3-KD cells. First panel: Mean control (grey) and SRSF3-KD (orange) SHAPE reactivities, calculated over 11nt sliding windows. Second panel: ∆SHAPE reactivity differences between control and SRSF3-KD. Regions with higher reactivity in control are marked with grey shading and regions with higher reactivity in SRSF3-KD with orange shading. Third panel: The SRSF3-KD to control reactivity ratios. The red boxes mark the mutated CNNC sites.",
    "ncbi_link": "miR-17: 407975
SRSF3: 6428"
  },
  {
    "caption": "B RT-qPCR quantification of Srsf3 and Cdkn1a (p21) mRNA levels in Srsf3-knockout (KO) and control (Ctrl) iPSCs (*p<0.05, ***<0.001, two-tailed unpaired Student's t-test, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "Cdkn1a: 12575
p21: 12575
Srsf3: 20383"
  },
  {
    "caption": "C Quantification of Cdkn1a mRNA expression by RT-qPCR during reprogramming in Srsf3-KO and control cells (***p<0.001, ****p<0.0001, Two-way ANOVA, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "Cdkn1a: 12575
Srsf3: 20383"
  },
  {
    "caption": "D RT-qPCR quantification of CDKN1A (p21) levels in HEK293T cells overexpressing empty vector, WT-miR-17-92, 17/20a-∆CNNC and total-CNNC∆ expression constructs (*p<0.05, **p<0.01, One-way ANOVA, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "CDKN1A: 1026
p21: 1026
miR-17: 407975"
  },
  {
    "caption": "E RT-qPCR quantification of CDKN1A (p21) levels in LIM1215 cells over expressing empty vector, SRSF3-FL and SRSF3-∆RS constructs (**p<0.01, One-way ANOVA, data as mean ± SEM, n=3, biological replicates). F RT-qPCR quantification of CDKN1A (p21) levels in LIM1215 cells overexpressing scrambled control, miR-17, miR-20a or miR-17+miR-20a mimics (**p<0.01, One-way ANOVA, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "miR-20a: 
CDKN1A: 1026
p21: 1026
miR-17: 407975
SRSF3: 6428"
  },
  {
    "caption": "A Western blot analysis of SRSF3 and CDKN1A expression in SRSF3-T2A-GFP overexpressing (SRSF3) and control (GFP) LIM1215 cells. GAPDH served as a loading control.",
    "ncbi_link": "GFP: 
SRSF3: 6428"
  },
  {
    "caption": "B TaqMan analysis of miR-17-92 miRNAs in SRSF3-T2A-GFP overexpressing (SRSF3-GFP) and GFP-only control (GFP) LIM1215 cells (*p<0.05, ****p<0.001, two-tailed unpaired Student's t-test, data as mean ± SEM, n=4, biological replicates).",
    "ncbi_link": "GFP: 
miR-17: 407975
SRSF3: 6428"
  },
  {
    "caption": "C RT-qPCR quantification of CDKN1A (p21) mRNA levels in SRSF3-T2A-GFP overexpressing (SRSF3-GFP) and control (GFP) LIM1215 cells (**p<0.01, two-tailed unpaired Student's t-test, data as mean ± SEM, n=3, biological replicates).",
    "ncbi_link": "GFP: 
CDKN1A: 1026
p21: 1026
SRSF3: 6428"
  },
  {
    "caption": "D Left: Schematic of the Firefly luciferase reporter constructs Right: Luciferase activity in SRSF3 overexpressing (SRSF3-GFP) and control (GFP) LIM1215 cells transfected with the reporter constructs (**p<0.01, ***p<0.001, two-tailed unpaired Student's t-test, data as mean ± SEM, n=4, biological replicates).",
    "ncbi_link": "GFP: 
luciferase: 
SRSF3: 6428"
  },
  {
    "caption": "F Quantification of fraction of cells in G1, S and G2 phases in SRSF3 overexpressing cells (SRSF3-GFP) relative to control (GFP) LIM1215 cells (*p<0.05, **p<0.01, two-tailed unpaired Student's t-test, data as mean ± SEM, n=4, biological replicates).",
    "ncbi_link": "GFP: 
SRSF3: 6428"
  },
  {
    "caption": "A, B RT-qPCR quantification of SRSF3 (A) and CDKN1A (B) mRNA levels in colorectal tumours and their paired normal samples (*p<0.05, **p<0.01, two-tailed unpaired Student's t-test, data as mean ± SEM, n=25, biological replicates). N=normal, T=tumour.",
    "ncbi_link": "CDKN1A: 1026
SRSF3: 6428"
  },
  {
    "caption": "D Association between SRSF3 expression and tumour (T) stage. T1 (n=3), T2 (n=5), T3 (n=11) and T4 (n=3) tumours, SRSF3 fold change as the dependent variable. Linear regression analysis (central band=median, boxes =25th and 75th percentile and whiskers=min and max, n=biological replicates). E Association between SRSF3 expression and tumour differentiation status. Moderately (Mod.) differentiated tumours (n=19) and poorly differentiated tumours (n=5), SRSF3 fold change as the dependent variable. Linear regression analysis (central band=median, boxes =25th and 75th percentile and whiskers=min and max; n=biological replicates).",
    "ncbi_link": "SRSF3: 6428"
  },
  {
    "caption": "G SRSF3 and CDKN1A expression in TCGA COAD data (version 2016_01_28; tumour n=459 and normal n=41 (biological replicates); RSEM, RNA-seq by Expectation Maximation; **p<0.01, two-tailed unpaired Student's t-test, central band=median, dotted lines =25th and 75th percentile).",
    "ncbi_link": "CDKN1A: 1026
SRSF3: 6428"
  },
  {
    "caption": "A. qPCR data comparing the expression of the CamkIIδc transgene in the brain and heart of 3 month old CamkIIδc TG mice; n=4/group; *P <0.05, Unpaired t-test, two-tailed. Note that the transgene is not detected in the brain.",
    "ncbi_link": "CamkII: 24246
CamkIIδc: 24246"
  },
  {
    "caption": "C. Ejection fraction, cardiac output and index are significantly decreased in CamkIIδc TG mice (n =8) when compared to control mice (n=5; *P <0.05, , **P<0.01, ***P<0.001, Unpaired t-test, two-tailed). Heart to body ratio, left ventricle to body ratio, and lung to body weight ratio are increased in CamkIIδc TG (n=8) compared to control (n=5; *P <0.05, **P<0.01, Unpaired t-test; two-tailed).",
    "ncbi_link": "CamkII: 24246"
  },
  {
    "caption": "H. qPCR quantification of selected genes reflecting ER-stress or protein methylation-related processes in CamkIIδc TG mice (n=4) and control mice (n=5). *p<0.05, ns = non-significant, Unpaired t-test; two-tailed. Data is normalized to Hprt1 expression.",
    "ncbi_link": "CamkIIδc: 24246
Hprt1: 15452"
  },
  {
    "caption": "D. The cumulative score of hippocampus-dependent search strategies during Barnes maze training is impaired in CamkIIδc TG (n = 16) when compared to control mice (n = 13; two-tailed, unpaired t-test, *p<0.05). E. Number of visits to escape hole during probe test to assay memory retrieval was impaired in CamkIIδc TG (n = 16) when compared to control mice (n = 13; two-tailed, unpaired t-test, *p<0.05). Data information: Bars and error bar indicates mean ± SEM. ",
    "ncbi_link": "CamkIIδc: 24246"
  },
  {
    "caption": "A. Hypergeometric overlap analysis comparing genes deregulated in CamkIIδc TG mice to genes differentially expressed in the hippocampal CA1 region of Kat2A, Kmt2A and Kmt2b knock out mice. Fisher's hypergeometric test, Benjamini-Hochberg (BH) correction.",
    "ncbi_link": "CamkIIδc: 24246
Kat2A: 14534
Kmt2A: 214162
Kmt2b: 75410"
  },
  {
    "caption": "E. H3K4me3 at TSS region of genes from RNA module1. Inset shows statistical comparisons among groups (One-way ANOVA, ***P<0.001, ****P<0.0001). Bars and error bars indicate mean ± SEM. Number of replicates analyzed for H3K4me3 profile at TSS (Wildtype vehicle: 3; CamkIIδc TG-vehicle n = 4; CamkIIδc TG-Vorinostat n = 4).",
    "ncbi_link": "CamkIIδc: 24246"
  },
  {
    "caption": "(B-E) Mouse embryonic fibroblasts (MEFs) were co-infected with shRNAs against Tnfaip2 or a scramble shRNA and reprogramming factors. The co-transduced cells were sorted and were reprogrammed for 14 days: (B) Representative images and (C) quantification of alkaline-phosphatase-positive (AP+) iPSC colonies on day 14 of reprogramming by transfection of 4 reprogramming factors (=4F: Oct4, Sox2, Klf4, c-Myc = OSKM) or 3 factors (=3F: OSK). [n=3 biological replicates per group; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by one-sided t-test analyzed by one-sided t-test with Holm-Sidak correction for multiple testing].",
    "ncbi_link": "Klf4: 16600
c-Myc: 17869
Oct4: 18999
Sox2: 20674
Tnfaip2: 21928"
  },
  {
    "caption": "Mouse embryonic fibroblasts (MEFs) were co-infected with shRNAs against Tnfaip2 or a scramble shRNA and reprogramming factors. The co-transduced cells were sorted and were reprogrammed for 14 days: (D) Representative FACS profiles",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(E) percentage of Oct4-GFP+ iPSCs obtained after 14 days of reprogramming of MEFs from Oct4-eGFP mice using 4F-transduction on day zero that were infected with shRNAs targeting Tnfaip2 or a scrambled shRNA control [n=5 biological replicates; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by one-sided t-test with Holm-Sidak correction for multiple testing].",
    "ncbi_link": "eGFP: 
Oct4: 18999
Tnfaip2: 21928"
  },
  {
    "caption": "]. (F) mRNA of Tnfaip2 was measured by RT-qPCR at the indicated days of reprogramming by 4F-transduction on day zero [n=3 biological replicates; log-transformed data were not normally distributed (P>0.05 as per Shapiro-Wilk test), P value for the upregulation of Tnfaip2 on consecutive test days-9,-12 and -14 was calculated starting with the probability of maximum rank-based difference, i.e. having two groups of three data points perfectly separating, p1,b = 0.1 (bidirectional) and p1,u = 0.05 (unidirectional); the probability of finding a triple series of max. difference starting at some timepoint is Ptriple,tp = p1,b · p1,u · p1,u, and finding such a triple somewhere across the 5-step time series is Ptriple = Ptriple,tp + 2 · (1- p1,u) · Ptriple,tp = 0.0007.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(C) RT-qPCR analysis of Smed-exoc3 mRNA expression of total RNA (whole body-derived) from exoc3(RNAi)-treated planarians compared to control-injected planarians on day-38 of the injection scheme [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test); data were analyzed by one-sided t-test].",
    "ncbi_link": "exoc3: "
  },
  {
    "caption": "(D) Representative photographs of exoc3(RNAi)-treated planarians vs. control planarians at day-38 of the injection protocol as shown in panel B (n=4 experimental replicates with 6-10 biological replicates per experiment, scale bar: 0.5 mm). Number ratios in the photographs depict the total number of animals showing the indicated phenotype.",
    "ncbi_link": "exoc3: "
  },
  {
    "caption": "Planarians were injected with Smed-exoc3 dsRNA = exoc3(RNAi) or with control gfp(RNAi) injections. (A) The representative photographs show staining for phosphorylation of 10th serine residue of Histone 3 (H3S10p, a stem cell marker in planarians) at days-38 of the injection protocol (n=3 experimental replicates with 8-10 biological replicates per experiment, scale bar: 0.5 mm).",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "exoc3(RNAi)-treated planarians versus gfp(RNAi)-treated controls were analyzed at the indicated time-points of the dsRNA injection protocol: (B) Quantification of H3S10p+ cells per mm2 in planarians at day-30, -34 and -38 of the injection protocol [n=3 experimental replicates with 5-7 biological replicates per experiment; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple comparisons].",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "FACS-based time-course analysis on changes in the fraction of somatic stem cells (X1-population) at indicated time points. Cells were obtained from whole body-trypsinized planarians of gfp(RNAi)-injected controls and exoc3(RNAi)-treated planarians and stained with the cytoplasmic dye Calcein-AM and the nuclear (DNA) dye Hoechst 33342: (C) Representative FACS profiles",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "RT-qPCR analysis for makers of differentiating progenitor cells from the epidermal lineage on total (whole body derived) RNA from exoc3(RNAi)-treated planarians (E) Expression analysis of differentiation marker prog-2 on day-38 of the injection scheme [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test and analyzed by one-sided t-test],",
    "ncbi_link": "exoc3: 
prog-2: "
  },
  {
    "caption": "(F) Expression analysis of marker genes of differentiated cells (prog-1 and Smed-odc-1; on day-30, -34 and -38 of the injection scheme [n= 3 biological replicates per group and time point except for prog-1 expression at day 38, which includes 6 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple comparisons]. For Smed-odc-1 log-transformed mean centered group data were normally distributed and and analyzed by multiple t-tests with Holm-Sidak correction for multiple comparisons].",
    "ncbi_link": "prog-1: 
odc-1: "
  },
  {
    "caption": "Planarians were injected with exoc3(RNAi) or with control gfp(RNAi) injections. Organ phenotypes were analyzed on day-38 of the injection protocol. Organ homeostasis was analyzed by staining against specific markers: (A) The structure of the brain/central nervous system (CNS) was analyzed by staining against synapsin (3C11). The cartoon represents the phenotypic change (upper panel). Representative photographs are shown in the lower panel (3 experimental replicates with 2-3 biological replicates per experiment, scale bar: 0.5 mm). Number ratios in the photographs indicate the total number of animals exhibiting the represented phenotype. There was a significant increase in the occurrence of atrophic cephalic ganglia and sensory neuron loss in exoc3(RNAi)-treated planarians vs. controls (cg: cephalic ganglia; sn: sensory neurons).",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "RNA-seq was conducted on freshly isolated X1 cells from exoc3(RNAi)-treated compared to X1 cells from gfp(RNAi)-treated planarians on day-38 of the injection protocol. The histograms depict the overlap (blue) of DEGs in X1 cells of Smed-exoc3-depleted planarians versus controls (n=3 biological replicates; adjusted P< 0.05) with genes expressed in the indicated sample sets of (A) neoblast stem cells",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "(B-E) The heat maps depict the intersection of DEGs with strong expression signals (log2 fold change > 0.5 or < -0.5) discovered in X1 cells of exoc3-depleted planarians versus controls (n= 3 biological replicates) with the indicated, previously published data sets on gene expression profiles in (B-D) neoblast cells or (E) differentiating progenitor cells of epidermal lineage. The colour scale represents the gene-wise z-score calculated from normalized gene expression levels while purple and green indicate upregulated and downregulated genes in X1 cells of exoc3-depleted planarians versus controls, respectively.",
    "ncbi_link": "exoc3: "
  },
  {
    "caption": "RNA-seq was conducted on freshly isolated X1 cells from exoc3(RNAi)-treated compared to X1 cells from gfp(RNAi)-treated planarians on day-38 of the injection protocol. The histograms depict the overlap (blue) of DEGs in X1 cells of Smed-exoc3-depleted planarians versus controls (n=3 biological replicates; adjusted P< 0.05) with genes expressed in the indicated sample sets of (F) differentiating progenitor cells of epidermal lineage from the indicated publications while the sum of overlapping (blue) and set-exclusive (grey) genes represents the total number of genes of a cluster that were analyzed in this study.",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "Planarians (S. mediterranea) were injected with exoc3(RNAi) or with control gfp(RNAi). (B) Representative photographs of morphology of exoc3 knockdown planarian vs. control planarian on days-29, -31 and -37 of the protocol Number ratios in the photographs indicate the photographically represented phenotypes.",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "Organ regeneration was analyzed by immunostaining of different organ compartments in regenerating exoc3(RNAi)-treated planarians vs. gfp(RNAi)-treated control on day 37 of the protocol (C) Eyes were analyzed by staining against VC1. Representative images are shown (3 experimental replicates with 4-5 biological replicates per experiment). Arrows point to photosensitive cells (ps); pigmentary cells (pc) and to the optic chiasm (oc). Number ratios in the photographs refer to planarians with regenerative defects for the indicated phenotype (scale bar: 0.5 mm).",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "Organ regeneration was analyzed by immunostaining of different organ compartments in regenerating exoc3(RNAi)-treated planarians vs. gfp(RNAi)-treated control on day 37 of the protocol (D) Representative photographs of staining with planarian pan-neural marker 3C11 (alias Synapsin) marking cephalic ganglia and sensory neurons Number ratios in the photographs refers to planarians with regenerative exhibiting the photographically represented phenotype, characterized by underdeveloped bilobed cephalic ganglia and atrophy of sensory neurons in exoc3(RNAi)-treated planarians versus controls (scale bar: 0.5 mm, cg: cephalic ganglia; sn: sensory neurons).",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "RNA-seq analysis was conducted on Tnfaip2-/- EBs vs. WT EBs on day-3 of differentiation induction of EBs (n=3 biological replicates). The heat maps depict the intersection of DEGs with the following gene sets (B) "stem cell maintenance: positive and negative regulators",",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "RNA-seq analysis was conducted on Tnfaip2-/- EBs vs. WT EBs on day-3 of differentiation induction of EBs (n=3 biological replicates). The heat maps depict the intersection of DEGs with the following gene sets ;, (C) "mesoderm development"",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "RNA-seq analysis was conducted on Tnfaip2-/- EBs vs. WT EBs on day-3 of differentiation induction of EBs (n=3 biological replicates). The heat maps depict the intersection of DEGs with the following gene (D) "ectoderm development" Tnfaip2 and 5 other stem cell-related genes (Tfcp2l1, Dppa3, Fbxo15, Zfp42 and Klf2) were additionally incorporated based on literature searches. The color scale represents the gene-wise z-score calculated from normalized gene expression levels. The asterisk refers to the gene identified in this study.",
    "ncbi_link": "Tnfaip2: 21928
Dppa3: 73708
Fbxo15: 50764
Klf2: 16598
Tfcp2l1: 81879
Zfp42: 22702"
  },
  {
    "caption": "(E) Representative image of immunofluorescence staining against the ectodermal marker (SOX1) and the mesodermal marker (T alias Brachyury) in WT and Tnfaip2-/- EBs on day-3 of differentiation induction. (3 repeat experiments were conducted on a total number of 9-10 EBs per genotype, scale bar: 20µm).",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(F) mRNA expression of Tnfaip2 measured by RT-qPCR in ESCs on the indicated days of differentiation induction of WT EBs [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test), the P value for the upregulation of Tnfaip2 on consecutive time points (day-0, -2 and -3) was calculated starting with the probability of maximum rank-based difference, i.e. having two groups of three data points perfectly separating, p1,b = 0.1 (bidirectional) and P1,u = 0.05 (unidirectional); the probability of finding a triple series of max. difference starting at some timepoint is Ptriple,tp = p1,b · p1,u · p1,u, and finding such a triple somewhere across the 4-step time series is Ptriple = Ptriple,tp + (1- p1,u) · Ptriple,tp = 0.0005.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(B) The Volcano plots show the differentially expressed proteins identified from the proteome analysis of Tnfaip2-/- EBs versus WT EBs at the indicated days after induction of differentiation. Vim (marked in blue asterisk) was the only protein that featured among top 100 differentially expressed proteins at all time points by implementing selection criteria of an average log2ratio > +/-1.2 and a -log10Qvalue <2. Vim expression was reduced at all timepoints of in vitro differentiation in Tnfaip2-/- EBs vs. WT EBs (n=5 biological replicates, see also Dataset EV8 for top 100 regulated proteins). Sphere size illustrates the magnitude of log2fold changes as does color coding: blue-downregulated proteins, red-upregulated proteins; log2fold marking by color intensity: strong intensity >2, medium intensity > 1.5, faded color >1.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(C) mRNA expression of Vim on indicated days of WT EB and Tnfaip2-/- EB differentiation (n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple testing).",
    "ncbi_link": "Tnfaip2: 21928
Vim: 22352"
  },
  {
    "caption": "FACS analysis of lipid droplet (LD) content of WT (blue) and Tnfaip2-/- (red) EBs by BODIPY493/503 staining at the indicated days after differentiation induction: (D) Representative FACS blot of BODIPY staining. Unstained WT EBs served as a negative control (grey).",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "FACS analysis of lipid droplet (LD) content of WT (blue) and Tnfaip2-/- (red) EBs by BODIPY493/503 staining at the indicated days after differentiation induction: (E) Quantification of staining intensity [n=3 independent cultures per genotype; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple comparisons].",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "Transmission Electron Microscopy (TEM) was used to determine the number of LDs in EB cultures derived from WT and Tnfaip2-/- ES cells on day-1 after differentiation induction. (n=5 independent cultures per genotype, n=100 images per replicate). (F) Representative micrographs of TEM analysis of EB cells of the indicated genotype. Yellow arrows point to LDs, scale bars: 1 µm.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "Electron Microscopy (TEM) was used to determine the number of LDs in EB cultures derived from WT and Tnfaip2-/- ES cells on day-1 after differentiation induction. (n=5 independent cultures per genotype, n=100 images per replicate). (G) Quantification of LDs per TEM field. Data were not normally distributed (P<0.05 as per Shapiro-Wilk test) and analyzed by Mann-Whitney test.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(H) UPLC-MS/MS analysis revealed a reduction in triacylglycerol (TAG) content in Tnfaip2-/- EBs compared to WT EBs at the indicated time points after differentiation induction [n=3 independent cultures of EBs per time point; data of EBs on day-0 to day-3 of differentiation were statistically analyzed; mean centered group data were normally distributed and (P>0.05 as per Shapiro-Wilk test) and analyzed by one-sided t-test with Holm Sidak correction for multiple testing].",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(A) Heatmap of CPT1A protein expression as measured in proteome analysis of Tnfaip2-/- and WT ESCs and during differentiation induction of EB cultures (n=5 biological replicates). The colour scale represents average log2ratios.",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "(B) Expression of Cpt1a mRNA as determined by qRT-PCR in WT and Tnfaip2-/- EBs at the indicated days of differentiation induction [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by multiple t-tests with Holm-Sidak correction for multiple comparisons].",
    "ncbi_link": "Tnfaip2: 21928
Cpt1a: 12894"
  },
  {
    "caption": "Differentiation-induced WT EBs and Tnfaip2-/- EBs were treated with palmitic acid (PA) and palmitoyl-L-carnitine (PC) (8μM each) or a vehicle control (C,D) The diameters of the rosette structure of differentiated WT EBs and Tnfaip2-/- EBs were measured on day-3 after differentiation induction. (n=3 repeat experiments with 7-62 EBs per experiment per group): (C) Representative photographs (scale bar: 0.02 mm) and (D) quantification of the diameter of the rosette structure of the indicated groups [data were not normally distributed (P<0.05 as per Shapiro-Wilk test) and thus analyzed by Mann-Whitney U test with Holm Sidak correction for multiple comparisons].",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "RNA-seq was conducted on day-3 of differentiation induction of Tnfaip2-/- EBs that were either treated with PA/PC or with a vehicle control (n=3 independent pools of 7-62 EBs per group). The heat maps depict the intersection of DEGs with the following gene sets (E) "stem cell maintenance: positive and negative regulators",",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "RNA-seq was conducted on day-3 of differentiation induction of Tnfaip2-/- EBs that were either treated with PA/PC or with a vehicle control (n=3 independent pools of 7-62 EBs per group). The heat maps depict the intersection of DEGs with the following gene sets ;, (F) "mesoderm development"",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "RNA-seq was conducted on day-3 of differentiation induction of Tnfaip2-/- EBs that were either treated with PA/PC or with a vehicle control (n=3 independent pools of 7-62 EBs per group). The heat maps depict the intersection of DEGs with the following gene sets (G) "ectoderm development". Five other stem cell-related genes (Tfcp2l1, Dppa3, Fbxo15, Zfp42 and Klf2) were additionally incorporated based on literature searches. The asterisks indicate the reverted changes in gene expression that were seen in Tnfaip2-/- EBs versus WT EBs The color scale represents the gene-wise z-score calculated from normalized gene expression levels.",
    "ncbi_link": "Tnfaip2: 21928
Dppa3: 73708
Fbxo15: 50764
Klf2: 16598
Tfcp2l1: 81879
Zfp42: 22702"
  },
  {
    "caption": "(H) Representative image of immunofluorescence staining against ectodermal marker (SOX1) and the mesodermal marker (T alias Brachyury) on day-3 of differentiation induction of Tnfaip2-/- EBs +/- co-treatment with PA/PC. Three repeat experiments were conducted with a total number of 9 EBs per group",
    "ncbi_link": "Tnfaip2: 21928"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were infected with shRNAs Cells were co-infected with 4 reprogramming factors (OSKM) (A) Representative images of AP staining of iPSC colonies",
    "ncbi_link": "eGFP: 
Oct4: 18999"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were infected with shRNAs Cells were co-infected with 4 reprogramming factors (OSKM) and double-infected cells were FACS sorted and grown for 14 days, when reprogramming efficiencies were determined by FACS. (B) representative FACS profiles of Oct4-positive iPSCs on day 14, (C) quantification of the percentage of Oct4-GFP+ iPSCs in MEF cultures that were infected with 2 different shRNAs targeting Vim or a scrambled shRNA control [n=3 biological replicates per group; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by t-test with Holm-Sidak correction multiple comparisons].",
    "ncbi_link": "eGFP: 
Oct4: 18999
Vim: 22352"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were infected with combinations of shRNAs. (D) Representative FACS profiles of mouse-specific pluripotency cell surface marker SSEA1+ iPSCs on day 14 of reprogramming and (E) quantification of the percentage of SSEA1+ iPSCs in MEF cultures that were infected with the indicated shRNAs targeting Vim and/or Tnfaip2 [n=5 biological replicates; data were normally distributed (P>0.05 as per Shapiro-Wilk test) but showed unequal variance; data were analyzed by Brown-Forsythe and Welch ANOVA and Dunnett's multiple comparisons test].",
    "ncbi_link": "eGFP: 
Oct4: 18999
Tnfaip2: 21928
Vim: 22352"
  },
  {
    "caption": "combinations of shRNAs. RT-qPCR was performed to determine (F) Vim mRNA expression in scrambled-shRNA infected MEFs versus shRNA-Tnfaip2-infected MEFs or Infected cells were purified by BFP-sorting on day-4 after infection [n=3 biological replicates; log transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by t-test with Holm-Sidak for multiple comparisons].",
    "ncbi_link": "BFP: 
Tnfaip2: 7127
Vim: 22352"
  },
  {
    "caption": "RT-qPCR was performed to determine (G) Tnfaip2 mRNA expression in scrambled-shRNA infected MEFs versus shRNA-Vim-infected MEFs. G) Infected cells were purified by BFP-sorting on day-4 after infection [n=3 biological replicates; log transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by t-test with Holm-Sidak for multiple comparisons].",
    "ncbi_link": "BFP: 
Tnfaip2: 21928
Vim: 22352"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were infected with a vector expressing the indicated shRNA in combination with the indicated cDNA (OE indicates overexpression), Cells were co-infected with 4 reprogramming factors (4F= Oct4, Sox2, Klf4, c-myc = OSKM) and double-infected cells were FACS sorted for analysis. (A) RT-qPCR analysis on day-4 after infection to determine RNA expression of Tnfaip2 or Vim in Tnfaip2-depleted cells with ectopic expression of Vim (left) or in Vim-depleted cells with ectopic expression of Tnfaip2 (right). Scramble shRNA (shScr)-infected MEFs served as a control [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by t-test].",
    "ncbi_link": "eGFP: 
Tnfaip2: 21928
Klf4: 16600
c-myc: 17869
Oct4: 18999
Sox2: 20674
Vim: 22352"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were infected with a vector expressing the indicated shRNA in combination with the indicated cDNA (OE indicates overexpression), (B) RT-qPCR analysis on day-4 after infection to determine RNA expression of Vim or Tnfaip2 in Tnfaip2-depleted cells with ectopic expression of Vim (left) or in Vim-depleted cells with ectopic expression of Tnfaip2 (right). Scramble shRNA (shScr)-infected MEFs served as a control [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by t-test].",
    "ncbi_link": "eGFP: 
Oct4: 18999
Tnfaip2: 21928
Vim: 22352"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were (A-D) infected with a vector expressing the indicated shRNA in combination with the indicated cDNA (OE indicates overexpression), ]. (C) Representative images of FACS profiles and (D) quantification of SSEA1+ iPSCs on day 14 after infection of MEF cultures with the indicated combination of shRNAs plus cDNAs (OE) or scrambled shRNA control [n=3 independent cultures per group; data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by one-way ANOVA and Dunnett's multiple comparison test ]",
    "ncbi_link": "eGFP: 
Oct4: 18999"
  },
  {
    "caption": "Oct4-eGFP reporter MEFs or WT MEFs were (E,F) infected with the indicated shRNA with or without combined treatment with Etomoxir - a chemical inhibitor of CPT1A. (E) Representative FACS profiles and (F) quantification of the percentage of SSEA1+ iPSCs in MEF cultures on day-18 after infection with shRNAs targeting Tnfaip2 or a scrambled shRNA control with or without continuous treatment with Etomoxir [n=5 biological replicates; data were not normally distributed (P<0.05 as per Shapiro-Wilk test) and analyzed by Mann-Whitney U test with Holm Sidak correction for multiple comparisons].",
    "ncbi_link": "eGFP: 
Oct4: 18999
Tnfaip2: 21928"
  },
  {
    "caption": "(C) RT-qPCR analysis of exoc3 mRNA expression in planarians of the indicated genotypes and treatment schedule",
    "ncbi_link": "exoc3: "
  },
  {
    "caption": "(E) Images of body plan maintenance in non-injured planarians that were injected with gfp-RNAi, exoc3-RNAi or exoc3-RNAi in combination with PA/PC injection Number ratios in the photographs indicate the total number of animals exhibiting the represented phenotype.",
    "ncbi_link": "exoc3: 
gfp: "
  },
  {
    "caption": "(F) RT-qPCR analysis of marker genes of early stem cell differentiation (prog-1 and prog-2) and late stem cell differentiation (Smed-odc1) in planarians exposed to the indicated treatment regiments on day-38 of the experiment as indicated in panel-B [n=3 biological replicates; log-transformed data were normally distributed (P>0.05 as per Shapiro-Wilk test) and analyzed by one-way ANOVA and Dunnett's multiple comparison test].",
    "ncbi_link": "prog-1: 
prog-2: 
odc1: "
  },
  {
    "caption": "B.  qRT-PCR expression  analysis of lncMN2 isoforms (left panel) and embedded miRNAs (right panel) in mESC  and EBs  differentiated for 6 days (EB6). Data, that are expressed as mean (error bars represent SD), were normalized over Atp50 mRNA (left) and snoRNA U25  (right) levels and reported as RNA fold over the control (mESC), set as 1. N=3 biological replicates. Data information: histogram Histogram dots represent single fields replicates. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, n.s.> 0.05 (two-tailed, unpaired Student's t-test).",
    "ncbi_link": "lncMN2: 100043213
Atp50: 28080
snoRNA U25: 115489078"
  },
  {
    "caption": "C. qRT-PCR expression  analysis of  lncMN2-202/203/204 isoforms (left panel), miR-325-3p (middle panel) and miR-384-5p (right panel) in WT, KO1 and KO2 EB6. Data information: histogram Histogram dots represent single fields replicates. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, n.s.> 0.05 (two-tailed, unpaired Student's t-test).",
    "ncbi_link": "lncMN2: 100043213
miR-325-3p: 723929
miR-384-5p: 723861"
  },
  {
    "caption": "E. Left: representative immunofluorescence  of the MN  marker Isl1 (red signals) in cells maintained in vitro for 14 days after EB6 dissociation (DIV14). DAPI counterstaining  in blue. Scale bar=100 mm.. Right: box plot shows the distribution of Isl1+ nuclei  with respect to the total  cell number marked with DAPI staining  in WT and in lncMN2   KO mutants (clone 1 and clone 2). Data are expressed as mean and error bars represent SD. The central band represents median and the whiskers represent the distribution that goes from the minimum value to the lower quartile and from the upper quartile to the maximum value. N=3 biological replicates and 10 fields were analyzed for each replicate. Scale bar=100 mm. Data information: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, n.s.> 0.05 (two-tailed, unpaired Student's t-test).",
    "ncbi_link": "lncMN2: 100043213"
  },
  {
    "caption": "B. qRT-PCR expression  analysis of  lncMN2-203 isoform, lncMN2-202/204,  miR-325-3p  and  miR-384-5p  embedded miRNAs in WT, ∆SP1 and ∆SP2 EB6. Data, that are expressed as mean (error bars represent SD), are normalized over Atp5o mRNA levels (for lncRNA isoform quantification) or over snoRNA U25  levels (for miRNA quantification) and are reported as RNA fold over the control (mESC), set as 1. N=3 biological replicates. Data are expressed as mean and error bars represent SD. Data information: histogram dots represent single fields replicates. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, n.s.> 0.05 (two-tailed, unpaired Student's t-test).",
    "ncbi_link": "lncMN2-202: 100043213
lncMN2-203: 100043213
Atp5o: 28080
snoRNA U25: 115489078
miR-325-3p: 723929
miR-384-5p: 723861
SP1: 20683
SP2: 78912"
  },
  {
    "caption": "C. Cytofluorimetric  analysis of cells from dissociated EB6. The right diagram reports the cell distribution (percentage of the peak) according to GFP  levels, from WT (gray line), ∆SP1 (purple line) and ∆SP2 (blue line) EB6. In the histogram aside, the percentage of GFP+ cells in WT, ∆SP1  and ∆SP2 is reported. Data are expressed as mean and error bars represent SD. N=3 biological replicates. Data are expressed as mean and error bars represent SD. Data information: histogram dots represent single fields replicates. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, n.s.> 0.05 (two-tailed, unpaired Student's t-test).",
    "ncbi_link": "SP1: 20683
SP2: 78912"
  },
  {
    "caption": "Percent colocalization of vDNA foci detected by click chemistry to PML at 3 dpi in SCG neurons with HSV-1EdC infected with ICP0-null mutant HSV-1, n212, or a rescued HSV-1 virus, n212R, in P6 SCG neurons treated with IFNα for 18 hours prior to infection or for 18hours at 3 days prior to infection. Each point represents the percentage of 20 vDNA foci that colocalized to PML from 3 biological replicates.",
    "ncbi_link": "ICP0: 2703389"
  },
  {
    "caption": "Number of Us11-GFP expressing neurons at 3 days post-LY294002-induced reactivation in P6 SCG neuronal cultures transduced with shRNA targeting PML for 3 days prior to infection with HSV-1 in the presence or absence of IFNα (150 IU/ml). n=9 biological replicates.",
    "ncbi_link": "PML: 18854"
  },
  {
    "caption": "Number of Us11-GFP expressing neurons at 3 days post-LY294002-induced reactivation in P6 SCG neuronal cultures transduced with shRNA targeting PML at 1 day post-infection with HSV-1 in the presence or absence of IFNα (150 IU/ml). n=9 biological replicates. Statistical comparisons were made using a Mann-Whitney test (ns not significant, * P<0.05).",
    "ncbi_link": "PML: 18854"
  },
  {
    "caption": "(A) Sanger sequence trace showing homozygosity for the c.469C>T mutation, predicting a stop codon in exon 6 of GRK2 (arrow).",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(D) Expression of GRK2 as measured by RT-PCR in three replicates each of control and R05-365A fibroblasts, demonstrating absence of GRK2 transcript in ATD cells. GAPDH served as a positive control.",
    "ncbi_link": "GAPDH: 2597
GRK2: 156"
  },
  {
    "caption": "(B) Picrosirius red staining of the femoral growth plates of a control and the ATD R05-365A fetus. The control growth plate shows normal architecture with clearly distinguishable reserve (R), proliferating (P) and hypertrophic (H) zones. A profound disruption of growth plate architecture is obvious in the GRK2-/- growth plate, which shows irregularly-shaped reserve zone chondrocytes, a lack of discernable proliferating chondrocytes and a significantly under-developed hypertrophic zone. Scale bars, 100 μm.",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(E) Alcian blue staining of the chicken limb bud micromasses treated with GRK2 inhibitor CMPD101. Note the gradual inhibition of the cartilage nodules with increasing concentration of CMPD101, quantified below. Mean ± SEM. Mann-Whitney U test; number of micromasses is indicated. A representative experiment of four (pH 2.5) and three (pH 1.0) is shown. Scale bar, 100 μm. (F) Alcian blue staining of the micromasses generated from Grk2+/+ and Grk2-/- NIH3T3 cells. Note the mildly weaker staining by alcian blue pH 2.5 and the nearly absent sulfation stained by alcian blue pH 1.0 in the Grk2-/- micromasses. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of micromasses is indicated. Scale bar, 1 mm. ",
    "ncbi_link": "Grk2: 110355"
  },
  {
    "caption": "(A,B) Defective GLI3 processing in GRK2-/- fibroblasts. Cells were serum-starved to induce cilia before treatment with the Hh pathway activator SAG (Smoothened agonist), and the whole cell lysates were immunoblotted for GLI3. Note the SAG-mediated downregulation of both full-length (FL) and repressor (R) GLI3 in control fibroblasts, demonstrating normal processing. There was no effect of SAG on GLI3 processing in GRK2-/- cells. A representative experiment of four is shown. (B) Quantitation of the GLI3FL to GLI3R ratio using densitometry. Mean ± SEM. Mann-Whitney U test; number of biological replicates is indicated.",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(C) Defective SAG response in GRK2-/- fibroblasts. Cells were treated with SAG for 24 hours. Transcript levels of GLI3 targets GLI1 and PTCH1 were determined by qRT-PCR; GAPDH was used for normalization. Note the SAG-mediated induction of GLI1 and PTCH1 expression in controls but not in GRK2-/- cells. Mean ± SEM. Mann-Whitney U test; number of biological replicates is indicated.",
    "ncbi_link": "GAPDH: 2597
GLI1: 2735
GLI3: 2737
GRK2: 156
PTCH1: 5727"
  },
  {
    "caption": "(D) Under-phosphorylation of Smoothened (SMO) in GRK2-/- fibroblasts. Lysates of SMO-transfected cells were resolved by the phospho(p)-shift PAGE and immunoblotted for SMO. The portion of pSMO analyzed by densitometry is shown. GRK2 add-back demonstrates a rescue of the pSMO in GRK2-/- fibroblasts. Mean ± SEM. Mann-Whitney U test; number of biological replicates is indicated.",
    "ncbi_link": "GRK2: 156
SMO: 6608"
  },
  {
    "caption": "Defective SMO accumulation in cilia of GRK2-/- fibroblasts. Cells were treated with SAG and immunostained for SMO, ARL13B and pericentrin. Note the failure in SMO accumulation in cilia of GRK2-/- cells (arrow). Scale bar, 2 µm (E).",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "Defective SMO accumulation in cilia of GRK2-/- fibroblasts. The percentage of SMO-positive cilia was calculated and plotted. Mean ± SEM. Welch´s t-test; number of biological experiments and the total numbers of analyzed cilia are indicated (F).",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "Defective SMO accumulation in cilia of GRK2-/- fibroblasts. The intensity of ciliary SMO was analyzed and plotted. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of biological experiments and the total numbers of analyzed cilia are indicated (G).",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "Defective SMO cilia accumulation in chondrocytes with downregulated GRK2. (E) Doxycycline (DOX)-inducible GRK2 downregulation in control human R00-082 chondrocytes, tested by western blot, normalized to actin and plotted below. Mean ± SEM. Welch´s t-test; number of biological experiments is indicated. shScr, scramble shRNA.",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(F) Cells pre-treated with DOX for three days were serum starved, SAG treated, stained and analyzed as in (A,B), and the intensity of ciliary SMO was analyzed and plotted. Note the impaired SMO translocation to cilia caused by GRK2 loss. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of biological experiments and the total numbers of analyzed cilia are indicated. Scale bar, 1 µm.",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(A) Control and GRK2-/- fibroblasts were transfected with the TOPflash Firefly (F) luciferase vector together with a control Renilla (R) luciferase vector, and the effect of Wnt3A on TOPflash transcriptional activation was determined by dual-luciferase assay. Note the impaired response to Wnt3A in GRK2-/- cells. Mean ± SEM. Welch´s t-test; number of biological experiments is indicated.",
    "ncbi_link": "luciferase: 
GRK2: 156"
  },
  {
    "caption": "C) Low phosphorylation (p) of Wnt3A co-receptor LRP6 as determined by western blot with pS1490- and pT1572-LRP6 specific antibodies, reduced LRP6 and DVL2 expression, and increased steady state phosphorylation of DVL2. (C) Densitometry of western blot results demonstrating decreased levels of LRP6 in GRK2-/- cells, lower response of GRK2-/- cells to Wnt3A by LRP6 phosphorylation at S1490, and tendency towards the similar defect at T1572. Densitometry also showed less of total DVL2 levels, and increased steady state pDVL2 in GRK2-/- cells. Mean ± SEM. Mann-Whitney U test; number of biological experiments is indicated.",
    "ncbi_link": "GRK2: 156"
  },
  {
    "caption": "(D) Loss of interaction between Frizzled 4 (FZD4) and ß-Arrestin 2 (ARRB2) in GRK2-/- fibroblasts. Proximity ligation assay (PLA) between expressed FZD4-GFP and ARRB2-Flag showed significantly reduced proximity events between the two proteins in GRK2-/- cells. White dashed lines outline the transfected cells. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of biological experiments and the total numbers of analyzed cells are indicated. Scale bar, 10 µm.",
    "ncbi_link": "ARRB2: 409
FZD4: 8322
GRK2: 156"
  },
  {
    "caption": "(A) Control (+/+) and Grk2-/- NIH3T3 cells were transfected with the TOPflash Firefly (F) luciferase vector together with a control Renilla (R) luciferase vector, treated with Wnt3A (100 ng/ml) for 24 hours and subjected to dual-luciferase assay. Note the impaired response to Wnt3A in Grk2-/- cells. Mean ± SEM. Mann-Whitney U test; number of biological experiments is indicated.",
    "ncbi_link": "luciferase: 
Grk2: 110355"
  },
  {
    "caption": "(B) Control (+/+) and Grk2-/- NIH3T3 cells were treated with 40 ng/ml Wnt3A for 1 hour. Note the lower LRP6 expression and inhibited Wnt3A-induced LRP6 phosphorylation in the Grk2-/- NIH3T3 cells. Mean ± SEM. Welch´s t-test; number of biological experiments is indicated.",
    "ncbi_link": "Grk2: 110355"
  },
  {
    "caption": "Loss of interaction between Frizzled 4 (FZD4) and ß-Arrestin 2 (ARRB2) in Grk2-/- NIH3T3 cells. (E) Proximity ligation assay (PLA) between expressed FZD4-GFP and ARRB2-Flag showed significantly reduced proximity events between the two proteins in Grk2-/- cells. White dashed lines outline the transfected cells. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of biological experiments and the total numbers of analyzed cells are indicated. Scale bars, 10 µm.",
    "ncbi_link": "Flag: 
GFP: 
ARRB2: 409
FZD4: 8322
Grk2: 110355"
  },
  {
    "caption": "Loss of interaction between Frizzled 4 (FZD4) and ß-Arrestin 2 (ARRB2) in Grk2-/- NIH3T3 cells. (F) GRK2 addback rescued the interaction. White dashed lines outline the transfected cells. Central band, median. Box, 1st-3rd quartile. Whiskers, 10%-90% percentile. Mann-Whitney U test; number of biological experiments and the total numbers of analyzed cells are indicated. Scale bars, 10 µm.",
    "ncbi_link": "Grk2: 110355
GRK2: 110355"
  },
  {
    "caption": "C. Analysis of TRAPPC2 (green), TRAPPC8 (blue) and TRAPPC9 (orange) localization at SGs upon TRAPPC2, TRAPPC4 TRAPPC8 and TRAPPC9 depletion. Mean ± s.e.m. n>100. *p<0.05; ns: not significant, One-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "TRAPPC2: 6399
TRAPPC4: 51399
TRAPPC8: 22878
TRAPPC9: 83696"
  },
  {
    "caption": "E. Analysis of TRAPPC2 localization at SGs upon CLIC1, CRYAB and ENO1 depletion. Mean ± s.e.m. n>100. ****p<0.0001; ns: not significant, One-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "CLIC1: 1192
CRYAB: 1410
ENO1: 2023"
  },
  {
    "caption": "D. Representative images of TRAPPC2 localization in Sec23AB-KD and Sec24ABCD-KD cells treated with SA. Cells were fixed and visualized by fluorescence microscopy using anti-TRAPPC2 Ab, anti-G3BP Ab (to label SGs) and DAPI (blue). Data information: Scale bars, 10 µm.",
    "ncbi_link": "Sec23A: 10484
Sec24A: 10802"
  },
  {
    "caption": "F. Representative images of Sec24C localization at SGs (stained for G3BP) in TRAPPC3-KD and TRAPPC2-KD cells treated with SA. Depletion of the entire TRAPP complex (via TRAPPC3 depletion) or of only TRAPPC2 reduces Sec24C recruitment. Graph, quantification of Sec24C at SGs, calculated as in (E). Mean ± s.e.m., n = 40-60 cells per experiment, N = 3. ****p< 0.0001, One-way ANOVA with Dunnett's multiple comparison test. Data information: Scale bars, 10 µm.",
    "ncbi_link": "TRAPPC2: 6399
TRAPPC3: 27095"
  },
  {
    "caption": "G. Representative images of Sec24C localization at SGs (stained for G3BP) in TRAPPC2-KO cells treated with SA. Data information: Scale bars, 10 µm.",
    "ncbi_link": "TRAPPC2: 6399"
  },
  {
    "caption": "B. Stabilizing TRAPP and COPII at the ERES prevents their relocalization to SGs. HeLa cells overexpressing GFP-Sar1H79G were treated with SA and immunostained for Sec24C, TRAPPC2, and eIF3, as indicated. Blue, DAPI. Graphs show quantification of Sec24C or TRAPPC2 at SGs in GFP-Sar1H79G-expressing cells. Data are the ratio between Sec24C or TRAPPC2 mean intensity in SG puncta and Sec24C or TRAPPC2 mean intensity at ERES, expressed as a percentage of the non-transfected (NT) cells. Mean ± s.e.m. n = 60-70, three independent experiments. ****p<0.0001, Student's unpaired two-tailed t-test. Data information; Scale bars, 10 µm.",
    "ncbi_link": "GFP: 
Sar1: "
  },
  {
    "caption": "C. Effect of Sec31A depletion on TRAPPC2 recruitment to SGs. Cells were mock-treated or KD for Sec31, treated with SA, and then immunostained for TRAPPC2 and eIF3 as indicated. Graphs, quantification of TRAPPC2 at ERES and SGs after SA treatment. Mean ± s.e.m., one representative experiment; n=60-80. ** p<0.001, ****p<0.0001, Student's unpaired two-tailed t-test. Data information; Scale bars, 10 µm.",
    "ncbi_link": "Sec31: 22872
Sec31A: 22872"
  },
  {
    "caption": "D. Effect of Sec31A depletion on Sec24C recruitment to SGs. Cells were mock-treated or KD for Sec31 and then immunostained for Sec24C and cTAGE5 (to stain ERES, top panels) and for eIF3 (bottom panels). Insets show eIF3. Graphs, quantification of Sec24C at ERES and in SGs after SA treatment. n=80. ****p<0.0001, Student's unpaired two-tailed t-test. Data information; Scale bars, 10 µm.",
    "ncbi_link": "Sec31: 22872
Sec31A: 22872"
  },
  {
    "caption": "E. Analysis of Sec24C recruitment to SGs in control and CDK1+2-KD HeLa cells. Different levels of CDK1+2 KD were achieved by transfecting cells with different amounts of siRNA for different times (2 nM 24 h; 5 nM 24 h; 5 nM 48 h; 20 nM 48 h) to give 50, 30, 20 and 10%, respectively, of the CDK1+2 levels in the control. CDK1+2 levels measured by qRT-PCR and Sec24C recruitment to SGs were evaluated from parallel cultures. Sec24C recruitment to SGs was performed by automated microscopy as described in (A) and is expressed as a percentage of mock (CTRL, set at 100%) ± s.d. N=8.",
    "ncbi_link": "CDK1: 983"
  },
  {
    "caption": "D. HeLa cells transfected with HA-hnRNPK were left untreated (Steady state) or treated with SA (300µM, 30 min) or SA+Dinaciclib (10 µM, 150 min) and then immunostained with anti-HA and anti-G3BP antibodies. Data information Scale bars, 10 µm.",
    "ncbi_link": "HA: 
hnRNPK: 3190"
  },
  {
    "caption": "E. TRAPPC2 interacts with hnRNPK. (Top) SDS-PAGE and Western blot analysis of endogenous hnRNPK after immunoprecipitation with an anti-TRAPPC2 Ab or IgG, and (bottom) after immunoprecipitation with an anti-HA Ab from cells transfected (+) or not (-) with hnRNPK-HA detected with the indicated antibodies.",
    "ncbi_link": "HA: 
hnRNPK: 3190"
  },
  {
    "caption": "F. Mock or hnRNPK KD cells treated with SA were immunostained for TRAPPC2 and eIF3. Data information: Scale bars, 10 µm.",
    "ncbi_link": "hnRNPK: 3190"
  },
  {
    "caption": "G. Mock or hnRNPK KD cells treated with SA were immunostained for Sec24C and G3BP. Data information: Scale bars, 10 µm.",
    "ncbi_link": "hnRNPK: 3190"
  },
  {
    "caption": "H. Graphs show quantification of TRAPPC2 and Sec24C redistribution to SGs in mock treated (CTRL) and hnRNPK KD cells. n>100, N=3 mean ± s.d. ***p<0.001.****p<0.0001, Student's unpaired two-tailed t-test.",
    "ncbi_link": "hnRNPK: 3190"
  },
  {
    "caption": "A. SG area in mock, TRAPPC2 TRAPPC3, TRAPPC8, and TRAPPC9-depleted cells treated with SA. Data are shown in box-and-whisker plots: Box-plot central line, median; box limits, upper and lower quartiles; whiskers show the minimum to maximum. N=3. ***p<0.001, ****p<0.0001, One-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "TRAPPC2: 6399
TRAPPC3: 27095
TRAPPC8: 22878
TRAPPC9: 83696"
  },
  {
    "caption": "Localization of Raptor (D) in mock, TRAPPC3-KD and TRAPPC2-KD HeLa cells treated with SA. G3BP was used to stain SGs. Scale bar, 10 µm. Each graph shows the quantification (mean intensity) of the respective protein in SG spots expressed as a percentage of the mock (TRL). Mean ± S.D. three independent replicates. *p<0.02; **p<0.009 in (D) , One-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "TRAPPC2: 6399
TRAPPC3: 27095"
  },
  {
    "caption": "Localization of RACK1 (E) in mock, TRAPPC3-KD and TRAPPC2-KD HeLa cells treated with SA. G3BP was used to stain SGs. Scale bar, 10 µm. Each graph shows the quantification (mean intensity) of the respective protein in SG spots expressed as a percentage of the mock (TRL). Mean ± S.D. independent replicates. , *p<0.05; ****p<0.0001 in (E), One-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "TRAPPC2: 6399
TRAPPC3: 27095"
  },
  {
    "caption": "K. Analysis of cell death in HeLa cells that were left untreated, treated with non-targeting siRNAs or siRNAs against TRAPPC2, and in two cell clones knocked out for TRAPPC2, with and without SA treatment. Mean ± s.d. of three independent replicates.",
    "ncbi_link": "TRAPPC2: 6399"
  },
  {
    "caption": "D. HeLa cells expressing VSV-G-UVR8 mEOS were left untreated or treated with SA alone or in combination with ISRIB (1 µM) (120 min ISRIB pre-treatment and 30 min SA+ISRIB) and then pulsed with blue light. Images were taken 10 min after the UV pulse and processed for staining with the indicated markers. E. Cells were treated with SA for 30 min, the SA was washed out (WO), and cells were left to recover for 120 min in the presence of cycloheximide, followed by a blue light pulse and processing for staining as described in (D). F. Quantification of VSV-G (mean intensity) in the Golgi area to the total VSV-G per cell under the conditions described in (D,E). Data are expressed as percentage of the control. Mean ± s.e.m. of three independent experiment. ****p<0.0001; ns: not significant, One-way ANOVA with Dunnett's multiple comparison test. Data information: Scale bars, 10 µm.",
    "ncbi_link": "VSV-G: 
UVR8: 836506"
  },
  {
    "caption": "G. HeLa cells transfected or not with WT GFP-Rab1B were left untreated or treated with SA and stained for GM130 and G3BP to monitor SGs. Dashed white line, WT GFP-Rab1B transfected cells. Scale bar, 10 µm. The graph shows quantification of Golgi objects in the different conditions. NT: non-transfected. Mean ± s.e.m. of three independent experiments. ****p<0.0001, Student's unpaired two-tailed t-test.",
    "ncbi_link": "GFP: 
Rab1B: 81876"
  },
  {
    "caption": "A, Distribution and classification of MAP4K3/GLK-positive cells in 20 ml BALFs  of all 12 individuals (A), Φ denotes macrophages; N denotes neutrophils; T denotes T cells; E denotes  epithelial cells.",
    "ncbi_link": "GLK: 8491
MAP4K3: 8491"
  },
  {
    "caption": "3 healthy controls (HC, #1 - #3), 3 mild  COVID-19 patients  (#1 - #3), and 6 severe COVID-19 patients  (#1 - #6) (B) from Cohort #1. Data were shown in UMAP. Single-cell  gene expression of MAP4K3  (GLK) in individual cells was shown in color scale.",
    "ncbi_link": "GLK: 8491
MAP4K3: 8491"
  },
  {
    "caption": "C, D The percentages of MAP4K3/GLK-positive KRT18+ epithelial  (C) or KRT18+ TPPP3+ ciliated epithelial cells  (D) in BALFs  from Cohort #1. Data information: In (C, D), *, P value < 0.05 (ANOVA test); §, P value < 0.05 (Dunnett's test).",
    "ncbi_link": "GLK: 8491
MAP4K3: 8491"
  },
  {
    "caption": "E, F GLK  mRNA levels in KRT18+ epithelial  (E) or KRT18+ TPPP3+ ciliated epithelial cells  (F) of Cohort #1. n (cell number) = 3, 14, 33 for HC; n = 65, 43, 74 for mild COVID-19 patients; n = 164, 62, 10, 4, 74, 66 for severe COVID-19 patients  (E). n = 25, 43, 36 for HC; n = 209, 244, 141 for mild COVID-19 patients; n = 189, 223, 330, 792, 80, 243 for severe COVID-19 patients  (F). Data information: In (E, F), *, P value < 0.05; **, P value < 0.01; ***, P value < 0.001; ****, P value < 0.0001 (Kruskal-Wallis test).",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "Real-time PCR  analysis of mouse GLK  mRNA levels in HCC827 lung epithelial cells infected with SARS-CoV-2 pseudovirus (B) The mRNA levels of GLK  were normalized to GAPDH  mRNA levels. n = 2 (technical replicates) per group. Data information: In (B data are presented as means. Data shown are representative results of three B, independent experiments.",
    "ncbi_link": "GAPDH: 2597
GLK: 225028"
  },
  {
    "caption": "Real-time PCR  analysis of mouse GLK  mRNA levels in HCC827 lung epithelial cells treated with the SARS-CoV-2 spike  protein (D). The mRNA levels of GLK  were normalized to GAPDH  mRNA levels. n = 2 (technical replicates) per group. Data information: In D), data are presented as means. Data shown are representative results of three D) independent experiments.",
    "ncbi_link": "GAPDH: 2597
GLK: 225028"
  },
  {
    "caption": "A ZetaView nanoparticle tracking analysis of particle numbers and sizes of CD63+ extracellular vesicles  (EVs) isolated from the supernatants of HCC827 lung epithelial  cancer cells, which were transfected with GLK  wild-type or GLK  kinase-dead (K45E) mutant. EVs  were isolated sequentially using ExoQuick kits and then ExoQuick ULTRA columns. Data information: Data shown are representative results of two (A) independent experiments.",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "B Immunoblotting  of ACE2  and CD63  proteins in exosomes  isolated from GLK  wild-type- or GLK  (K45E) kinase-dead-overexpressing HCC827  cells. Exosomes  were isolated sequentially using ExoQuick kits and then ExoQuick ULTRA columns. Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins. Data information: Data shown are representative results of three (B, independent experiments.",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "D Confocal microscopy analysis of Flag-tagged ACE2  proteins (red) in recipient cells after incubation with exosomes  for 72 h. Exosomes  were isolated sequentially from the supernatants of Flag-ACE2-overexpressing or GFP-GLK  plus Flag-ACE2-coexpressing HCC827  cells using ExoQuick kits and then ExoQuick ULTRA columns. Arrows denote Flag-tagged ACE2  proteins. Original magnification, ×630; scale bars, 10 μm. Data information: Data shown are representative results of three D, independent experiments.",
    "ncbi_link": "Flag: 
GFP: 
ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "D Immunoblotting  analyses of the endogenous ACE2, ACE1, CD147, and tubulin  proteins, as well as the transfected Flag-GLK  proteins in HCC827 lung epithelial cells, which were transfected with either GLK  wild-type or kinase-dead (K45E) mutant. Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins. Data information: Data shown are representative results of three D, independent experiments.",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "E Immunoblotting  of Flag-tagged ACE2  (anti-Flag), Myc-tagged GLK  (anti-GLK), and tubulin  proteins from HEK293T  cells co-transfected with Flag-ACE2  plus increasing amounts of Myc-GLK  plasmids. Data information: Data shown are representative results of three E, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "F Immunoblotting  of ACE2, GLK, and tubulin  proteins in the lung  tissues of wild-type or GLK-deficient mice. Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins. Data information: Data shown are representative results of three F, independent experiments.",
    "ncbi_link": "GLK: 225028"
  },
  {
    "caption": "G Cycloheximide pulse-chase experiments in HEK293T  cells. Immunoblotting  of Flag-tagged ACE2  (anti-Flag), Myc-tagged GLK  (anti-GLK), and tubulin  proteins from HEK293T  cells co-transfected with Flag-ACE2  and Myc-GLK. Transfected cells were treated with 100 μg/ml cycloheximide  (CHX) for up to 24 h. Data information: Data shown are representative results of three G, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "H Flag-tagged ACE2  proteins were immunoprecipitated from lysates of HEK293T  cells co-transfected with Flag-ACE2  and Myc-GLK, followed by immunoblotting with anti-Lsy48-linked ubiquitination  or anti-Flag  antibody. Cells were treated with 25 μM MG132  for 2 h before being harvested. NS, normal serum. Data information: Data shown are representative results of three H, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "I, J Cell entry efficiencies of SARS-CoV-2 pseudovirus (I) or VSV-G  pseudovirus (J) into GLK  wild-type- or GLK  (K45E)-overexpressing HCC827 epithelial cells were measured by luciferase activity and presented as relative light units (RLU) at 24 h post infection. n = 3 (biological replicates). Data information: In (I, J), data are presented as means ± SEM. **, P value < 0.01 (ANOVA test); §§, P value < 0.01 (Dunnett's test). Data shown are representative results of three I, J) independent experiments.",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "A Immunoblotting  analyses of ACE2  and Flag-tagged GLK  in HCC827  cells transfected with ether Flag-GLK  or Flag-GLK  (K45E) kinase-dead mutant. For immunoblotting  of phosphorylated ACE2, Phos-tagged  SDS-PAGE gel (Phos-tagTM) was used, followed by immunoblotting  with anti-ACE2  antibody. Asterisk denotes unglycosylated ACE2  proteins. Data information: Data shown are representative results of three (A independent experiments.",
    "ncbi_link": "Flag: 
GLK: 8491"
  },
  {
    "caption": "C  Mass spectrometry analysis of GLK-phosphorylated ACE2  proteins after in vitro kinase assays. ACE2  Ser776 and Ser783 residues were phosphorylated  by GLK  wild-type but not GLK  (K45E) kinase-dead mutant.",
    "ncbi_link": "GLK: 8491"
  },
  {
    "caption": "F Immunoblotting  analyses of Myc-tagged GLK, Flag-tagged ACE2, and tubulin  proteins in HEK293T  cells co-transfected with Flag-ACE2   wild-type or individual ACE2   (S776/783A, S776A, or S783A) mutants plus either empty vector or Myc-GLK. Data information: Data shown are representative results of three F, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "G Immunoblotting  analyses of Flag-tagged ACE2   and tubulin  proteins in HEK293T  cells transfected with Flag-ACE2   wild-type or individual phosphomimetic ACE2   (S776/783E, S776E, or S783E) mutants. Data information: Data shown are representative results of three G, independent experiments.",
    "ncbi_link": "Flag: 
ACE2: 59272"
  },
  {
    "caption": "H Flag-tagged ACE2   proteins were immunoprecipitated  from lysates of HEK293T  cells transfected with Flag-ACE2   wild-type or a phospho-mimetic ACE2   (S776/783E) mutant, followed by immunoblotting  with anti-Lsy48-linked ubiquitination  or anti-Flag  antibody. Cells were treated with 25 μM MG132  for 2 h before being harvested. Data information: Data shown are representative results of three H) independent experiments.",
    "ncbi_link": "Flag: 
ACE2: 59272"
  },
  {
    "caption": "B Immunoblotting of Myc-tagged ACE2  (anti-ACE2), Flag-tagged UBR4  (anti-Flag), and tubulin  proteins from HEK293T  cells co-transfected with Myc-ACE2  and Flag-UBR4. Arrowhead denotes Myc-tagged ACE2  proteins; asterisk denotes endogenous ACE2  proteins. Data information: Data shown are representative results of three B, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
UBR4: 23352"
  },
  {
    "caption": "C Immunoblotting  of Flag-tagged ACE2  (anti-Flag), Myc-tagged UBR4  (anti-Myc), and tubulin  proteins from HEK293T  cells co-transfected with Flag-ACE2  and Myc-UBR4. The co-transfected cells were treated with 25 μM MG132  for 2 h before being harvested. Data information: Data shown are representative results of three C, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
UBR4: 23352"
  },
  {
    "caption": "D Flag-tagged ACE2  proteins were immunoprecipitated  from lysates of HEK293T  cells co-transfected with Flag-ACE2  and Myc-UBR4, followed by immunoblotting  with anti-Lsy48-linked ubiquitination, anti-Myc, or anti-Flag  antibody. Cells were treated with 25 μM MG132  for 2 h before being harvested. Data information: Data shown are representative results of three D, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
UBR4: 23352"
  },
  {
    "caption": "F Mass spectrometry analysis of the ACE2  peptides containing ubiquitination  residues from Flag-ACE2-transfected HEK293T  cells treated with 25 μM MG132  for 2 h.",
    "ncbi_link": "Flag: 
ACE2: 59272"
  },
  {
    "caption": "G Immunoblotting  analyses of Flag-tagged ACE2, Myc-tagged UBR4, and tubulin  proteins in HEK293T  cells co-transfected with Flag-ACE2  wild-type or individual (K26R, K94R, K112R, or K114R) mutants plus either empty vector or Myc-UBR4. Data information: Data shown are representative results of three G, independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
UBR4: 23352"
  },
  {
    "caption": "H Flag-tagged ACE2  proteins were immunoprecipitated  from lysates of HEK293T  cells co-transfected with Flag-ACE2  wild-type or Flag-ACE2  (K26/112/114R) mutant plus Myc-UBR4  plasmids, followed by immunoblotting  with anti-Lsy48-linked ubiquitination  or anti-Flag  antibody. Cells were treated with 25 μM MG132  for 2 h before being harvested. Data information: Data shown are representative results of three H) independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
ACE2: 59272
UBR4: 23352"
  },
  {
    "caption": "Wild-type and hACE2 KI mice  were intranasally infected with  SARS-CoV-2 pseudovirus. Infection  efficiencies of SARS-CoV-2 pseudovirus into mouse  tissues were measured by IVIS  and presented as luminescence counts at 4 days post infection  (B). Data information: WT, wild-type mice; KI, hACE2 knockin mice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Wild-type and hACE2 KI mice  were intranasally infected with SARS-CoV-2 pseudovirus. Immunoblotting  of ACE2, GLK, and tubulin  proteins in the lung  tissues of infected or non-infected mice  (C). Data information: Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins. WT, wild-type mice; KI, hACE2 knockin mice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Wild-type and hACE2  KI mice  were intranasally infected with SARS-CoV-2 pseudovirus. Representative immunohistochemistry  of the SARS-CoV-2 spike  protein (in red) and GLK  protein (in green) in the lung  tissues of the infected hACE2 KI and wild-type mice  (D). Scale bars, 20 μm (D). Data information: WT, wild-type mice; KI, hACE2 knockin mice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Wild-type and hACE2 KI mice  were intranasally infected with SARS-CoV-2  pseudovirus. Immunoblotting  of CD9  and mouse/human ACE2  in the exosomes  isolated from the BALFs  (E) of the infected mice. Data information: Arrowhead denotes glycosylated ACE2  proteins; asterisk denotes non-glycosylated ACE2  proteins. WT, wild-type mice; KI, hACE2 knockin mice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Wild-type and hACE2 KI mice  were intranasally infected with  SARS-CoV-2 pseudovirus. Exosomes  were isolated sequentially using ExoQuick kits and then ExoQuick ULTRA columns. The hACE2-containing exosomes  in the lung  tissues of wild-type and hACE2 KI mice  were determined by in situ proximity ligation assays (PLA) of close proximity (<40 nm) between hACE2  and the exosome  marker CD9  using anti-human ACE2  antibody plus anti-CD9  antibody (F). Scale bars, 20 μm (F). Data information: WT, wild-type mice; KI, hACE2 knockin mice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Human ACE2  transgenic (EF1α-hACE2 Tg) mice  were intranasally infected with 2x105 pfu of live  SARS-CoV-2. The survival rates  of in EF1α-hACE2 Tg mice  challenged with/without SARS-CoV-2 were monitored (H). Data information: Tg, transgenic mice.",
    "ncbi_link": "ACE2: 59272
EF1α: 1915"
  },
  {
    "caption": "Human ACE2  transgenic (EF1α-hACE2 Tg) mice  were intranasally infected with 2x105 pfu of live SARS-CoV-2. The lung  tissues of infected mice  at day 3 days post infection were collected and then analyzed by immunohistochemistry  (IHC) and PLA  assays. Representative IHC  data of hACE2 (in red) and GLK  (in green) in the lung  tissues of the infected wild-type and EF1α-hACE2 Tg mice  were shown (I). Cell nuclei  were stained  with DAPI. Original magnification, ×630. Scale bars, 10 μm. Data information: WT, wild-type mice; Tg, transgenic mice.",
    "ncbi_link": "ACE2: 59272
EF1α: 1915"
  },
  {
    "caption": "Human ACE2  transgenic (EF1α-hACE2 Tg) mice  were intranasally infected with 2x105 pfu of live SARS-CoV-2. The hACE2-containing exosomes  in the lung  tissues of infected wild-type and EF1α-hACE2 Tg mice  were determined by PLA  (J). Original magnification, ×630. Scale bars, 10 μm. Data information: WT, wild-type mice; Tg, transgenic mice.",
    "ncbi_link": "ACE2: 59272
EF1α: 1915"
  },
  {
    "caption": "K, Adoptive transfer of ACE2-containing exosomes  facilitates SARS-CoV-2 pseudovirus infection. Serum exosomes  (exo) isolated from wild-type (WT) mice  and hACE2 KI/activated GLK   transgenic (PolII-GLK   E351K Tg) mice  were adoptively transferred into wild-type recipient mice  every 3 days for 12 days, followed by SARS-CoV-2 pseudovirus infection. Infection  efficiencies into mouse  tissues were measured by IVIS  and presented as luminescence counts at 3 days post infection  (K). Data information: WT, wild-type mice; KI, hACE2 knockin mice. Tg, transgenic mice.",
    "ncbi_link": "ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "L Adoptive transfer of ACE2-containing exosomes  facilitates  SARS-CoV-2 pseudovirus infection. Serum exosomes  (exo) isolated from wild-type (WT) mice  and hACE2  KI/activated GLK   transgenic (PolII-GLK   E351K Tg) mice  were adoptively transferred into wild-type recipient mice  every 3 days for 12 days, followed by SARS-CoV-2 pseudovirus infection. hACE2-containing exosomes  in the lung  tissues of exosome-recipient wild-type mice  were determined by PLA  using anti-human ACE2  antibody plus anti-CD9   antibody (L). Scale bars, 10 μm (L). Data information: WT, wild-type mice; KI, hACE2 knockin mice. Tg, transgenic mice.",
    "ncbi_link": "ACE2: 59272
GLK: 8491"
  },
  {
    "caption": "(b) in N2 wild type (black diamonds) and ung-1 mutants (red squares), (c) following the depletion of EXO-3 (red triangles), APN-1 (blue circles) or control RNAi (L4440, black diamonds) in the N2 wild-type background, and (d) in msh-2(ok2410) (orange triangles), msh-6(pk2504) (green circles) and mlh-1(ok1917) (grey squares) mutants.",
    "ncbi_link": "APN-1: 174291
mlh-1: 176783
msh-2: 171938
msh-6: 171914
ung-1: 176633"
  },
  {
    "caption": "(e) Western blottings showing expression of MSH-6 protein in the wild type strain grown on E. coli expressing control (N2) or the indicated RNAi, as well as in msh-6(pk2504) and msh-2(ok2410) mutants (top panel), and expression of MSH-2::GFP fusion protein in transgenic worms grown on E. coli expressing RNAi for MSH-2, MSH-6 or empty vector control as indicated (lower panel). Actin was used as the loading control.",
    "ncbi_link": "MSH-2: 171938
msh-2: 171938
msh-6: 171914"
  },
  {
    "caption": "(f) F1 survival after depletion of MSH-2 and MSH-6 in the mlh-1(ok1917) mutant. (g,h) F1 survival after depletion of the AP endonucleases EXO-3 and APN-1 in (g) the msh-6(pk2504) or (h) msh-2(ok2410) mutant background. Kruskal-Wallis one-way analysis on ranks (P=0.963 and P=0.985 in h and g, respectively). Mann-Whitney rank-sum test failed to identify a difference in median survival after depleting EXO-3 in the msh-6 mutant (g, P=0.929). (i) F1 survival following depletion of the indicated genes in exo-3(tm4374) mutants. (j) F1 survival in msh-6(pk2504), exo-3(tm4374) and exo-3;msh-6 double mutants. (k) F1 survival in exo-3(tm4374), mlh-1(ok1917) and exo-3;mlh-1 double mutants. All survival curves (b-d,f-k) show the mean±s.d. for each data point from three independent experiments.",
    "ncbi_link": "APN-1: 174291
exo-3: 173069
EXO-3: 173069
mlh-1: 176783
MSH-2: 171938
msh-2: 171938
MSH-6: 171914
msh-6: 171914"
  },
  {
    "caption": "(c) Quantification of the fraction (%) of 5-FU-treated embryos that contain RPA-1-positive foci in N2, mlh-1(ok1917) and exo-1(tm1842) mutants fed control (L4440) or RNAi targeting APN-1 (apn-1).",
    "ncbi_link": "APN-1: 174291
apn-1: 174291
exo-1: 176765
mlh-1: 176783"
  },
  {
    "caption": "(d) Immunofluorescence showing CHK-1 phosphorylation at Ser139 in response to 5-FU in N2 but not in msh-6(pk2504) mutants or in N2 after apn-1(RNAi) (scale bars, 5 μm). (e) Quantification of the fraction (%) of 5-FU-treated embryos with phospho-CHK-1 foci.",
    "ncbi_link": "apn-1: 174291
msh-6: 171914"
  },
  {
    "caption": "(f) Western blottings showing H1X.101 levels in N2 and msh-6 mutants, treated (+) or not (−) with 5-FU. Actin was used as loading control. (g) Quantification of H1X.101 levels relative to actin in control versus 5-FU-treated worms. (b,c,e,g) Bar graphs show the mean±s.d. from three independent experiments.",
    "ncbi_link": "msh-6: 171914"
  },
  {
    "caption": "(d) F1 survival measured after depletion of BEC-1 (red triangles) and ATG-7 (blue squares) as compared with worms fed control RNAi (black diamonds). The survival curve shows the mean±s.d. for each data point from three independent experiments.",
    "ncbi_link": "ATG-7: 834630
BEC-1: 177345"
  },
  {
    "caption": "(f) Immunofluorescence showing anti-VPS-34 staining in N2 and atl-1(tm853) embryos in the absence or presence of 5-FU (scale bar, 5 μm).",
    "ncbi_link": "atl-1: 179352"
  },
  {
    "caption": "(h) Induction of autophagy (% GFP-positive embryos) in control (GFP::LGG-1) and atm-1(gk186) mutants (atm-1; GFP::LGG-1). (e,g,h) Bar graphs represent mean±s.d. from three independent experiments.",
    "ncbi_link": "atm-1: 3565793"
  },
  {
    "caption": "(c) F1 survival after control (black diamonds) or bec-1 RNAi (red squares) in N2 and msh-6(pk2504) mutants. The survival curve shows the mean±s.d. for each data point from three independent experiments.",
    "ncbi_link": "bec-1: 177345
msh-6: 171914"
  },
  {
    "caption": "(c) N2 or msh-6(pk2504) embryos were continuously monitored under differential interference contrast microscopy (scale bars, 5 μm) from the three-cell stage until completion of the four-cell stage. Magnified images of representative nuclei are shown. (d) The fraction of embryos with visible, enlarged nucleoli (arrows) after 5-FU treatment was scored. Bar graphs represent mean±s.d. from three independent experiments.",
    "ncbi_link": "msh-6: 171914"
  },
  {
    "caption": "e) Western blots showing absence of LC3-II accumulation in U2OS cells transfected with siRNA against MSH-2. The same blot probed with anti-MSH-2 antibodies confirm efficient knockdown. (f) Quantification of LC3-II levels in cells transfected with control or MSH-2 siRNA with or without FU treatment for 24 h.",
    "ncbi_link": "MSH-2: 4436"
  },
  {
    "caption": "(g) Immunofluorescence showing reduced accumulation of LC3 puncta in U2OS cells transfected with siRNA against MSH-2. (h) Quantification of LC3-positive puncta in cells treated as in g.",
    "ncbi_link": "MSH-2: 4436"
  },
  {
    "caption": "(i) Quantification of normalized RPS3 protein level (black bars) or RPS3 mRNA level (white bars) in U2OS cells after 48 h 5-FU treatment. RPS3 mRNA levels were determined by quantitative real-time reverse transcriptase-PCR.",
    "ncbi_link": "RPS3: 6188"
  },
  {
    "caption": "Quantitative RT-PCR showing the mRNA expression levels of IL-1β, IL-18, ASC, CASP1 and NLRP3 in MDMs treated with P22077 (2.5 µM) and/or LPS (1 μg/mL; 4 hrs.), as indicated. Bars represent the mean fold increase from an untreated (UT) control",
    "ncbi_link": "ASC: 51008
CASP1: 834
IL-18: 3606
IL-1β: 3553
NLRP3: 114548"
  },
  {
    "caption": "Western blots of supernatants and cell lysates from THP-1 cells engineered by CRISPR/Cas9 to induce USP7 and/or USP47 KOs. Deficiency of both USP7 and USP47 was induced by doxycycline (Doxy) treatment (1 µg/mL; 3 days), as indicated. All cells were differentiated with PMA and either unprimed or LPS-primed (1 μg/mL, 4 hrs.) and treated with nigericin (10 μM, 45 mins.), as indicated. Bands in the figure represent: Pro-IL-1β (31 kDa); mature IL-1β (mIL-1β, 17 kDa); pro-caspase-1 (pro-Casp-1; 45 kDa); mature caspase-1 (mCasp-1; 20 kDa); USP7 and USP47. β-actin is shown as a loading control. Blots are representative of at least 3 independent experiments.",
    "ncbi_link": "Cas9: 
CRISPR: 
USP47: 55031
USP7: 7874"
  },
  {
    "caption": "Western blot analysis of MsrB2 and LC3 I/II in Meg-01 cell after shMsrB2 transfection (72 hrs). Cells were then treated with H2O2 (1 mM for 1 hr) alone or with NAC (100 μM for 30 min). GAPDH was used as the loading control. Quantification and analysis of individual groups. GAPDH served as the loading control. (shMsrB2 vs. shCon; *p=0.024, shMsrB2/H2O2 vs. shCon/H2O2; *p=0.0295, shMsrB2/H2O2/NAC vs. shCon/H2O2/NAC **p=0.0100, n=3)",
    "ncbi_link": "MsrB2: 22921"
  },
  {
    "caption": "Western blot analysis of MsrB2, pp53(S15) and LC3 I/II in Meg-01 cell after 25 mM HG treatment for 24 hrs. GAPDH was used as the loading control. Quantification analysis on individual groups. GAPDH served as the loading control. (MsrB2: shCon/HG vs. shCon; **p=0.0017, shMsrB2/HG vs. shCon/HG; *p=0.0189, pp53: shMsrB2/HG vs. shCon/HG; *p=0.0317, LC3II: shCon/HG vs. shCon; *p=0.0215, shMsrB2/HG vs. shCon/HG; *p=0.0158, n=3) The nonparametric t test was performed for comparisons of 2 groups. Analysis was performed with Prism software (GraphPad Software, Inc, La Jolla, CA). A difference of P<0.05 was considered significant.",
    "ncbi_link": "MsrB2: 22921"
  },
  {
    "caption": "Levels of reactive oxygen species (ROS) quantified in the platelets using the fluorescent dye DCFH-DA. (ROS; *p=0.0139, MsrB2 fl/fl n=5, MsrB2 -/- n=6)",
    "ncbi_link": "MsrB2: 76467"
  },
  {
    "caption": "C. Representative image and quantification of mitochondrial apoptosis, measured in freshly isolated platelets from the MsrB2 knockouts and age matched floxed mice. Results are expressed as % apoptotic cells. (TMRE; *p=0.0118, MsrB2 fl/fl n=5, MsrB2 -/- n=5)",
    "ncbi_link": "MsrB2: 76467"
  },
  {
    "caption": "MsrB2 ubiquitination assay after transient transfection of MsrB2-GFP (1µg) with RFP empty vector (E.V.) or RFP-Parkin (3µg) in HEK293. After transfection (48hrs), an IP was performed using GFP-Trap bead, followed by Western blot analysis using UB and MsrB2 and Parkin antibodies. The nonparametric t test was performed for comparisons of 2 groups. Analysis was performed with Prism software (GraphPad Software, Inc, La Jolla, CA). A difference of P<0.05 was considered significant.",
    "ncbi_link": "GFP: 
RFP: 
MsrB2: 22921
Parkin: 5071"
  },
  {
    "caption": "F. Multiplex in situ RNA hybridization  of ACE2 and SARS-CoV-2 of mock-infected and  infected 2D ileum organoids at 12 hpi  and 24 hpi. White arrows point at SARS-CoV-2-infected cells. A representative image is shown.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "A. Human ileum-derived organoids were seeded in 2D on iBIDi chamber slides. 12 and 24 hpi cells were fixed and the amount of SARS-CoV-2 infected cells (red) and the induction of ISG15 (white) was analyzed by single molecule RNA FISH. Nuclei were visualized with DAPI  (blue). White arrows indicate SARS-CoV-2 positive cells. N=3 biological samples. Representative  image is shown. Scale bar=100 um.",
    "ncbi_link": "ISG15: 9636"
  },
  {
    "caption": "D.  T84 IRF3 knock-out cells were infected with SARS-CoV-2 or  human astrovirus 1 at an MOI=3. 24 hpi, cells were incubated in the presence or absence of 2000 IU/mL of  IFNβ1. 12 h post-treatment RNA was harvested and the induction of ISG15 was analyzed by q-RT-PCR and normalized to the housekeeping gene TBP. N=3 biological replicates. Error bar indicates standard deviation. Statistics were determined by unpaired t-test.",
    "ncbi_link": "IRF3: 3661
ISG15: 9636
TBP: 6908"
  },
  {
    "caption": "E. T84 IRF3 knock-out cells were infected with SARS-CoV-2 or  human astrovirus 1  at an MOI=3. 24 hpi, cells were fixed and stained for either the SARS-CoV-2 N protein or for human astrovirus 1 (HAstV1) capsid protein. N=3 biological replicates. Representative image is shown. Scale bar=100 um.",
    "ncbi_link": "IRF3: 3661"
  },
  {
    "caption": "G. T84 MX-1 mcherry were  infected with SARS-CoV-2 at an MOI=3 or MOI=1. 24 hpi cells were incubated in the presence or absence of 2000 IU/mL of IFNβ1. 12 h post-treatment cells were fixed and stained  for SARS-CoV-2 N protein. The number of MX-1 positive, SARS-CoV-2  positive and double positive cells was quantified. N=3 biological replicates were performed. Error bar indicates standard deviation.",
    "ncbi_link": "mcherry: 
MX-1: 4599"
  },
  {
    "caption": "Immunoblot analysis of LC3B and GABARAP lipidation in wild-type (WT) and ATG16L1-KO HEK293A cells, with or without stimulation for 2h as indicated. BafA1 stands for Bafilomycin A1. Gamma-Tubulin (γ-Tubulin) is loading control. Densitometry analysis of lipidated LC3B (LC3B-II) to γ-tubulin (normalized to untreated WT cells) from immunoblots in (A). Data information: All data presented as mean + SEM, from n = 3 independent experiments. P-value determined using two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "LC3B/GABARAP lipidation in ATG16L1- and ATG5-KO HEK293A cells treated for 2h as indicated. Vinculin is loading control. Cell lysates were immunoblotted for the specified proteins. Ratio of LC3B-II to Vinculin quantified from immunoblots in (C) and normalized to MC3 treated ATG16L1 KO cells. Data information: All data presented as mean + SEM, from n = 3 independent experiments. P-value determined using two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant.",
    "ncbi_link": "ATG16L1: 55054
ATG5: 9474"
  },
  {
    "caption": "Immunoblot analysis of LC3B and GABARAP lipidation from WT, ATG16L1-KO (L1-KO), ATG16L2-KO (L2-KO), TECPR1-KO (TEC-KO), ATG16L1/L2-DKO (L1/L2-DKO), ATG16L1/TECPR1-DKO (L1/TEC DKO), and ATG16L1/L2/TECPR1-TKO (L1/L2/TEC-TKO) PC-3 cells, treated as indicated for 2h, were immunoblotted for the indicated proteins. Vinculin is loading control. MRT68921 and SAR405 are ULK and VPS34 inhibitors, respectively. Data information: All data presented as mean + SEM, from n = 3 independent experiments. P-value determined using two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant.",
    "ncbi_link": "ATG16L1: 55054
L1: 55054
ATG16L2: 89849
L2: 89849
TEC: 25851
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in ATG16L1-KO and ATG16L1/TECPR1-DKO HEK293A cells with or without TECPR1 rescue, treated as indicated for 2h. Cell lysates were immunoblotted against the indicated proteins. Vinculin is loading control. Ratio of LC3B-II to Vinculin quantified from immunoblots in (G) and normalized to ATG16L1-KO cells treated with MC3. Data information: All data presented as mean + SEM, from n = 3 independent experiments. P-value determined using two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant.",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in WT, ATG16L1/TECPR1-DKO HeLa cells with and without EGFP-TECPR1 or EGFP-ATG16L1β rescue, treated for 2h as indicated. Cell lysates were immunoblotted for the indicated proteins. γ-Tubulin is loading control. Ratio of LC3B-II to γ-Tubulin quantified from immunoblots in (A) and normalized to untreated WT cells. (Data presented as mean + SEM, n = 3 independent experiments, P-value from two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant).",
    "ncbi_link": "ATG16L1β: 
EGFP: 
ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "Confocal images of ATG16L1/TECPR1-DKO HeLa cells expressing mScarlet-LC3B, with or without EGFP-TECPR1, treated for 2h with Cy5-labeled MC3 particles (left) or LLOMe (right) as indicated. Scale bars: 10 µm.",
    "ncbi_link": "EGFP: 
ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "Confocal time lapse images of ATG16L1/TECPR1-DKO HeLa cells, showing localization of mScarlet-LC3B and EGFP-TECPR1, after treatment with 400 μM LLOMe. Scale bar: 10 µm.",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "Immunoblot analysis of LC3B/GABARAP lipidation in ATG16L1-KO HEK293A cells, treated with 400µM LLOMe for indicated periods of time. γ-Tubulin is loading control. Ratio of LC3B-II to γ-Tubulin quantified from immunoblots in (E) and normalized to 2hr (120min) LLOMe treatment. (Data presented as mean + SEM, n = 4 independent experiments, P-value from two-way ANOVA followed by Tukey's multiple comparisons test).",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "Time series of confocal images showing redistribution of EqtSM-mCherry (sphingomyelin (SM) probe) and EGFP-TECPR1 in ATG16L1/TECPR1-DKO cells with doxycycline-inducible (dox, 2μg/ml) expression of EqtSM-mCherry cells following treatment with 400µM LLOMe. Scale bar: 10 µm.",
    "ncbi_link": "EqtSM: 
mCherry: 
ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in ATG16L1- and TECPR1-KO HEK293A cells with or without dox-inducible (2μg/ml) expression of nSMase2-mCherry, treated for 2h as indicated. Cell lysates were immunoblotted against the indicated proteins. γ-Tubulin is loading control. Ratio of LC3B-II to γ-Tubulin quantified from immunoblots in (B) and normalized to untreated ATG16L1-KO cells. (Data presented as mean + SEM, n = 3 independent experiments, P-value from two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant).",
    "ncbi_link": "mCherry: 
ATG16L1: 55054
nSMase2: 55512
TECPR1: 25851"
  },
  {
    "caption": "Confocal images of ATG16L1/TECPR1-DKO HeLa cells expressing EGFP-TECPR1, with or without dox-inducible (2μg/ml) nSMase2 overexpression, treated for 2h as indicated. Scale bars: 10 µm. Beeswarm-Superplot displaying mean number of EGFP-TECPR1 dots per cell per image of data represented in (E) quantified by automated analysis using CellProfiler. Mean ± SEM from each independent experiment (3/group) presented as large data points, with the black line corresponding to the mean of means. Individual data points (small) corresponding to single images are color-coded and superimposed according to the biological replicate they originate from. Total cells per condition/images per condition: 952/30 (LLOMe treated - nSMase2) and 1056/30 (LLOMe treated + nSMase2) were analyzed. (P-values determined using Student's unpaired t test).",
    "ncbi_link": "ATG16L1: 55054
nSMase2: 55512
TECPR1: 25851"
  },
  {
    "caption": "Immunoblot analysis of LC3B/GABARAP lipidation in ATG16L1-KO or ATG16L1/TECPR1-DKO HEK293A cells with or without rescue with TECPR1 (WT), TECPR1 W77A, TECPR1 W154A, TECPR1 W829A or TECPR1 F908A, and treated with 400 µM LLOMe for 2h. γ-Tubulin is loading control. Ratio of LC3B-II to γ-Tubulin quantified from immunoblots in (C) and normalized to ATG16L1-KO cells. Data information: All data presented as mean + SEM (in (D) n = 3 independent experiments. P-values determined using one-way ANOVA followed by Tukey's multiple comparisons test in D and H; ns= not significant.",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in ATG16L1/TECPR1-DKO HEK293A cells rescued with TECPR1 (WT), TECPR1 W77A, TECPR1 W829A or TECPR1 W77A/W829A (WAWA), and treated with 400 µM LLOMe for 2h. γ-Tubulin is loading control.",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "Maximum intensity projection of confocal images of HeLaK cells expressing EGFP-TECPR1 (WT) or W77A/W829A (WAWA) mutant, with or without 400µM LLOMe for 30min. Nuclei were counterstained with Hoechst 33342 (in blue). Scale bar: 10μm Beeswarm-Superplot displaying mean number of EGFP-TECPR1 dots per cell per image of data represented in (G) quantified by automated analysis using CellProfiler. Mean ± SEM from each independent experiment (3/group) presented as large data points, with the black line corresponding to the mean of means. Individual data points (small) corresponding to single images are color-coded and superimposed according to the biological replicate they came from. Total cells per condition/images per condition: 2502/59 (WT untreated), 2549/48 (WT LLOMe), 2256/59 (WAWA untreated) and 2816/59 (WAWA LLOMe) were analyzed.",
    "ncbi_link": "EGFP: 
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in WT, ATG16L1/TECPR1-DKO, ATG16L1-KO and TECPR1-KO HeLa cells with or without dox-inducible (2μg/ml) expression of mCherry-SopF, treated as indicated for 2h, were immunoblotted for the indicated proteins. γ-Tubulin is loading control. MRT68921 and SAR405 are ULK and VPS34 inhibitors, respectively. Ratio of LC3B-II to γ-Tubulin or Vinculin quantified from immunoblots in (A) and normalized to WT monensin treated cells. (Data presented as mean + SEM, n = 3 independent experiments, P-value from two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant). (Data has skewed distribution. P-values were determined with Kruskal-Wallis followed by Dunn's multiple comparisons test).",
    "ncbi_link": "mCherry: 
SopF: 
ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "LC3B/GABARAP lipidation in WT, ATG16L1/TECPR1-DKO, ATG16L1-KO and TECPR1-KO HeLa cells with or without dox-inducible (2μg/ml) expression of mCherry-SopF, treated as indicated for 2h, Cell lysates were immunoblotted for the indicated proteins. γ-Tubulin is loading control. MRT68921 and SAR405 are ULK and VPS34 inhibitors, respectively. Ratio of LC3B-II to γ-Tubulin or Vinculin quantified from immunoblots in (A) and normalized to WT monensin treated cells. (Data presented as mean + SEM, n = 3 independent experiments, P-value from two-way ANOVA followed by Tukey's multiple comparisons test; ns= not significant). (Data has skewed distribution. P-values were determined with Kruskal-Wallis followed by Dunn's multiple comparisons test).",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "Confocal images of WT and TECPR1-KO cells with or without dox-inducible (2μg/ml) expression of mCherry-SopF, treated as indicated for 2h. Nuclei were counterstained with Hoechst 33342 (in blue). Scale bar: 10μm Beeswarm-Superplot displaying number of LC3 puncta per cell in the images represented in (E) quantified by automated analysis using CellProfiler. Mean ± SEM from each independent experiment (3/group) presented as large data points, with the black line corresponding to the mean of means. Individual data points (small) corresponding to single cells are color-coded and superimposed according to the biological replicate they originated from. Total cells per condition/images per condition: 1169/30 (WT LLOMe), 1064/29 (WT-mcherrySopF LLOMe), 692/23 (TECKO LLOMe) and 983/30 (TECKO-mcherrySopF untreated) were analyzed. (Data has skewed distribution. P-values were determined with Kruskal-Wallis followed by Dunn's multiple comparisons test).",
    "ncbi_link": "mCherry: 
mcherry: 
SopF: 
TEC: 25851
TECPR1: 25851"
  },
  {
    "caption": "Assessment of protein-DNA interactions using Electro-mobility shift assays (EMSA). IRDye700 labelled dsDNA (at 2 nM) was incubated with indicated amounts of non/single/double-ubiquitinated ID2 (His6-TEV-V5-FANCI and FLAG-FANCD2) protein complexes (I+D2, IUb+D2Ub, I+D2Ub­) or ubiquitinated FLAG-FANCD2 (D2Ub). Mixes were ran on non-denaturing gels, and the resolved free- and protein-bound DNA bands were visualized using an infrared scanner. EMSA gels of ID2 complexes are representative of 3 replicate experiments.",
    "ncbi_link": "D2: 2177"
  },
  {
    "caption": "FANCD2 ubiquitination cannot robustly enhance ID2-DNA binding when complexed with IR1285Q, as determined by PIFE. Left: Fluorescence changes when IRD700-labelled dsDNA (at 125 nM) is incubated at increasing concentrations of IR1285Q +D2 or IR1285Q +D2Ub (complex concentrations ranging from 1.54 nM to 3.8 µM). Measurement of fluorescence enhancement for each protein combination was conducted for two separately prepared complexes (two technical repeats) and all data points for each protein-combination were used in fitting of a one-site binding model. Right: Bar graph showing mean apparent Kd values calculated from the one-site binding model. Error bars: Asymmetric 95% confidence intervals from non-linear regression (22 data points each). IWT + D2 and IWT + D2Ub previously calculated curves and corresponding Kd values (from data points shown in Figure 1A) are also shown for comparison.",
    "ncbi_link": "D2: 2177"
  },
  {
    "caption": "FANCD2 ubiquitination cannot robustly enhance ID2-DNA binding when complexed with IR1285Q, as determined by EMSAs. IRDye700-labelled dsDNA (at 2 nM) was incubated with indicated amounts of ID2 (His6-FANCI or His6-FANCIR1285Q mixed with non-ubiquitinated or ubiquitinated FLAG-FANCD2. Mixes were ran on non-denaturing gels, and the resolved free- and protein-bound DNA bands were visualized using an infrared scanner. Gels shown are representative of two replicate experiments.",
    "ncbi_link": "FLAG: 
His: 
FANCD2: 2177
FANCI: 55215"
  },
  {
    "caption": "A. BAZ2A expression is higher in ESC+2i than in differentiated cells (neural progenitors, NPC). Left panel. BAZ2A mRNA levels were measured by qRT-PCR and normalized to Rps12 mRNA and to ESC+2i. Average values of three independent experiments. Error bars represent s.d. and statistical significance (P-values) was calculated using the paired two-tailed t-test (*** < 0.001). Right panel. Western blot showing BAZ2A protein levels in ESC+2i and NPC. Tubulin is shown as a protein loading control.",
    "ncbi_link": "BAZ2A: 116848
Rps12: 20042"
  },
  {
    "caption": "C. siRNA-knockdown efficiency of BAZ2A shown by qRT-PCR and western blot. BAZ2A mRNA levels were measured by qRT-PCR and normalized to Rps12 mRNA and to each ESC line. Average values of three independent experiments. Error bars represent s.d. and statistical significance (P-values) was calculated using the paired two-tailed t-test (**** < 0.0001). Right panel. Western blot showing BAZ2A protein levels. Tubulin is shown as a protein loading control.",
    "ncbi_link": "BAZ2A: 116848
Rps12: 20042"
  },
  {
    "caption": "D. BAZ2A knockdown affects proliferation of ESC+2i but not of ESC+serum. Data represent relative cell numbers after 3 days of siRNA treatment and were normalized to ESC transfected with siRNA-Control. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (** < 0.01; ns, non-significant).",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "E. BAZ2A is expressed at similar levels in both ESC+2i and ESC+serum. Left panel. BAZ2A mRNA levels were measured by qRT-PCR and normalized to Rps12 mRNA and to ESC+2i. Average values of three independent experiments. Error bars represent s.d. Right panel. Western blot showing BAZ2A protein levels in ESC+2i and ESC+serum. Tubulin and histone H3 are shown as a protein loading controls.",
    "ncbi_link": "BAZ2A: 116848
Rps12: 20042"
  },
  {
    "caption": "F. BAZ2A is required for the differentiation of ESC+2i but not of ESC+serum. Representative images of alkaline phosphatase staining of ESC and cells after 3 days of differentiation upon culture in completed medium containing 10% serum and in the absence of LIF.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "H. Western blot showing BAZ2A protein levels in two BAZ2A-KO ESC lines obtained via CRISPr/Cas9 directly in ESC+serum. PARP1 is shown as a protein loading control.",
    "ncbi_link": "Cas9: 
CRISPr: 
BAZ2A: 116848"
  },
  {
    "caption": "I. Cell proliferation is not affected in BAZ2A-KO ESC+serum. Data represent relative cell numbers 2 days culture starting with the same number of cells. Average values of four independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns, non-significant).",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "J. Representative images of wt and Baz2a-KO ESC+serum before and after transition in 2i conditions.",
    "ncbi_link": "Baz2a: 116848"
  },
  {
    "caption": "A. Volcano plot showing fold change (log2 values) in transcript level of ESC+2i and ESC+serum with two consecutive treatments with siRNA-control and siRNA-Baz2a, each one lasting for 4 days. Gene expression values of three replicates were averaged and selected for 1.5 fold changes and P < 0.05. Statistical significance (P-values) was calculated using R package DEseq2.",
    "ncbi_link": "Baz2a: 116848"
  },
  {
    "caption": "B. Validation by qRT-PCR of genes regulated by BAZ2A in ESC+2i but not in ESC+serum (upregulated genes in ESC+2i upon BAZ2A-KD are labeled in blue, downregulated genes are in red). Nanog, Rex1 and Actin B (ActB) are shown as genes not regulated by BAZ2A. mRNA levels were normalized to Rps12 mRNA and to ESCs transfected with siRNA-Control. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (* < 0.05, ** < 0.01, *** < 0.001). Data without P values are statistically non significant.",
    "ncbi_link": "Actin B: 11461
ActB: 11461
BAZ2A: 116848
Nanog: 71950
Rex1: 66932
Rps12: 20042"
  },
  {
    "caption": "A. Western blot showing equal BAZ2A levels in wt-ESC and F/H-BAZ2A ESC line containing FLAG-HA sequences at the N-terminus of both Baz2a alleles. Whole cell lysates from equivalent amounts of cells were analysed. SNF2H, and Tubulin are shown as protein loading controls.",
    "ncbi_link": "FLAG: 
HA: 
Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "B. Anti-FLAG ChIP of wt-ESCs and F/H-BAZ2A-ESCs cultured in 2i or serum. Data were measured by qPCR and normalized to input and a control region that is not bound by BAZ2A. Average values of three independent experiments. Error bars represent s.d. and statistical significance (P-values) was calculated using the paired two-tailed t-test (* < 0.05, ** < 0.01).",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "D. Pearson correlation heat map for the indicated ChIPseqs in ESC+2i. BAZ2A ChIPseqs were performed with FLAG antibodies in F/H-BAZ2A-ESCs cultured in 2i or serum and with HA antibodies in F/H-BAZ2A-ESC+2i. Data of H3K4me3, H3K27ac and H3K27me3 are from this work. H3K36me3, H3K9me3 and H3K4me1 values in ESC+2i were taken from published data sets",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "H. Representative images showing that genes regulated by BAZ2A are enriched in H3K27me3, depleted of H3K27ac and not bound by BAZ2A.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "I. Heat map profiles of H3K27me3 and H3K27ac at ±5 kb from the TSS of genes differentially regulated by BAZ2A in ESC+2i and random genes. Differentially regulated genes are shown as upregulated or downregulated in ESC+2i upon BAZ2A knockdown. Data were ranked by H3K27me3 levels. Transcription start site (TSS).",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "D. H3K27ac correlates with differential accessible sites between ESC+2i and ESC+serum. Boxplot showing the mean values of normalized H3K27ac at ATAC peaks (+/- 500bp) that are increased and decreased in ESC+2i compared to ESC+serum, respectively. ESCs were subjected to two consecutive treatments with siRNA-control and siRNA-Baz2a, each one lasting for 4 days. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (*** < 0.001). Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes.",
    "ncbi_link": "Baz2a: 116848"
  },
  {
    "caption": "E. BAZ2A depletion increases chromatin accessibility only in ESC+2i. Numbers of significant changed ATAC peaks in ESC+2i and ESC+serum upon BAZ2A knockdown and their localization according to compartmentalization. F. Average density plots of normalized ATAC read counts over differential ATAC peaks of ESC+2i and ESC+serum treated with siRNA-Baz2a and siRNA-control over changed ATAC peaks. The signal is plotted over +/- 1kb centered on the ATAC peak. ",
    "ncbi_link": "Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "G. The distances of increased (IAS) and decreased (DAS) chromatin accessibility sites in BAZ2A-depleted ESC+2i to the nearest gene promoter (+/- 5kb of TSS) were calculated. Distances in bp to the nearest promoter of genes upregulated (UP), downregulated (DOWN) or not affected (NOT) upon BAZ2A knockdown in ESC+2i are plotted. Statistical significance (P-values) for the experiments was calculated using the unpaired two-tailed t-test (** < 0.01). Error bars represent s.d. The mean is represented by a horizontal line.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "H. Genomic annotation of IAS and DAS in ESC+2i depleted of BAZ2A perfomed with ChIPseeker",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "I. Fold-enrichment relative to expected of regions with increased chromatin accessibility (IAS) and upregulated genes upon BAZ2A KD at sub-regions within compartment A and B (center, inside and boundaries). Compartments smaller than 500 kb were excluded from the analysis. Statistical significance (P-values) was calculated with permutation test (ns: non significant, * < 0.05, *** < 0.001).",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "J. BAZ2A-upregulated genes are enriched in the B compartment. Numbers of BAZ2A-regulated genes upregulated and downregulated upon BAZ2A knockdown in ESC+2i including their localization according to compartmentalization.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "K. Active histone marks increase in the B compartment upon BAZ2A knockdown. Boxplots indicating the log2 fold-changes of normalized H3K27ac and H3K4me3 read counts in ESC+2i treated with siRNA-Baz2a and siRNA-control at boundaries and centers of A and B compartments. ). Statistical significance (P-values) for the experiments was calculated using the unpaired two-tailed t-test (*** < 0.001, * < 0.05). Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes.",
    "ncbi_link": "Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "A. Hi-C contact matrices for chromosome 1 of ESC+serum, ESC+2i/siRNA-control and ESC+2i/siRNA-Baz2a showing the presence of strong long-distance contacts corresponding to regions in A compartment bound by BAZ2A in ESC+serum. Cells were subjected to two consecutive treatments with siRNA-control and siRNA-Baz2a, each one lasting for 4 days. Eigenvector values are shown. Increase in far-cis contacts in ESC+2i upon BAZ2A-KD are highlighted with a rectangle. B. Relative contact frequencies over genomic distances in ESCs treated with siRNA-control and siRNA-BAZ2A. Statistical significance (P-values) was calculated using the Kolmogorov-Smirnov test. C. Boxplot indicating differences in eigenvector values at boundaries and centers of A and B compartments. Differences in eigenvector values were calculated from HiC data sets from ESC+2i treated with siRNA-Baz2a and siRNA-control. Statistical significance (P-values) for the experiments was calculated using the unpaired two-tailed t-test (*** < 0.001, ns: non significant). Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes. ",
    "ncbi_link": "Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "A. Western blot showing total levels of H3K27me3 in ESC+2i transfected with siRNA-control and siRNA-Baz2a. Histone H3 is shown as a protein loading control.",
    "ncbi_link": "Baz2a: 116848"
  },
  {
    "caption": "B. Scatterplot showing the changes in H3K27me3 upon BAZ2A depletion in ESC+2i and ESC+serum. ESCs were subjected to two consecutive treatments with siRNA-control and siRNA-Baz2a, each one lasting for 4 days. Mean of normalized H3K27me3 read counts in ESC+2i and ESC+serum treated with siRNA-control or siRNA-Baz2a over all TSSs (+/- 1kb) were calculated. Log2-fold changes of (siRNA-Baz2a/siRNA-control) are plotted relative to the mean of normalized H3K27me3 occupancies. The red line represents the mean of H3K27me3 fold-changes.",
    "ncbi_link": "Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "D. Average density plot of ChIPseq read counts of H3K27me3 at -/+ 5 kb from the TSS of refseq genes in ESCs treated with siRNA-control or siRNA-Baz2a Q1: first quartile corresponding to sequences with high H3K27me3 content. Q2-4: quartiles 2-4 corresponding to sequences with low H3K27me3 content.",
    "ncbi_link": "Baz2a: 116848"
  },
  {
    "caption": "E. ChIP-qPCR of H3K27me3 in ESC+2i and ESC+serum treated with siRNA-control or siRNA-Baz2a. Data were measured by qPCR and normalized to input and to Tshz1 value in control cells. Control represents an intergenic sequence that does not contain H3K27me3. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns: non significant, * < 0.05, ** < 0.01, *** < 0.001).",
    "ncbi_link": "Baz2a: 116848
Tshz1: 110796"
  },
  {
    "caption": "F. Boxplot showing changes in H3K27me3 in ESC+2i upon BAZ2A at BAZ2A-regulated and random genes. Mean of normalized H3K27me3 read counts in ESC+2i treated with siRNA-control or siRNA-Baz2a over TSSs (+/- 1kb) of upregulated, downregulated and random genes were calculated. Log2-fold changes of (siRNA-Baz2a/siRNA-control) are plotted. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (** < 0.01 and *** < 0.001). Box plots depict the minimum and maximum values. The mean is represented by a horizontal line within the boxes.",
    "ncbi_link": "Baz2a: 116848
BAZ2A: 116848"
  },
  {
    "caption": "G. Average density and heatmap profile of H3K27me3 transition state regions marked by CTCF sites in ESC+2i or ESC+serum transfected with siRNA-control or siRNA-Baz2a. Data were ranked by H3K27me3 content in the corresponding siRNA-control ESCs. Cluster 1 represents high to low H327me3 transition whereas Cluster 2 shows low to high H3K27me3 levels.",
    "ncbi_link": "Baz2a: 116848
CTCF: 13018"
  },
  {
    "caption": "H. H3K27me3 ChIP-qPCR in ESC+2i (top panel) or ESC+serum (bottom panel) transfected with siRNA-control or siRNA-Baz2a. Values show H3K27me3 occupancy at four sequences (#1-#4) with elevated H3K27me3 at CTCF boundary (H3K27me3hi/CTCF). Control represents an intergenic sequence that does not contain H3K27me3. Data were measured by qPCR and normalized to input and to sequence #1 value in control cells. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns: non significant, * < 0.05, ** < 0.01).",
    "ncbi_link": "Baz2a: 116848
CTCF: 13018"
  },
  {
    "caption": "I. Hi-C contact matrices for a zoomed in region on chromosome 6 containing HoxA cluster (10-kb resolution in upper panels, 5 kb resolution in lower panels). Blue arrows (A, B, and C) indicate gain or increase of contacts in ESC+siRNA-Baz2a compared to control cells (siRNA-control). The orange arrow (D) indicates loss or decrease in contacts.",
    "ncbi_link": "Baz2a: 116848
HoxA: 111336"
  },
  {
    "caption": "B. BAZ2A-interacting proteins on chromatin. Mass spectrometry analysis of FLAG immunoprecipitates from wt and F/H-BAZ2A ESC+2i. Values of peptide number are shown as the difference between peptides obtained in FLAG-IP of F/H-BAZ2A and wt ESC chromatin extracts. Data are from three independent experiments. The proteins found enriched in FLAG-IP of F/H-BAZ2A ESCs in all three experiments are shown. Further BAZ2A-interacting proteins identified in only two or one of the immunoprecipitation (IP) experiments Error bars represent s.d.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "C. Anti-HA IP of wt- and F/H-BAZ2A-ESC+2i and ESC+serum. Western blot shows the interaction of BAZ2A with SNF2H, TOP2A and SMC1a.",
    "ncbi_link": "BAZ2A: 116848"
  },
  {
    "caption": "D. TOP2A and BAZ2A regulate gene expression in ESC+2i via a shared pathway. qRT-PCR of genes regulated by BAZ2A in ESC+2i (left panel) and in ESC+serum (right panel) upon TOP2A or BAZ2A knockdown by siRNA. ESCs were treated with the corresponding RNAs for 4 days. Upregulated genes in ESC+2i upon BAZ2A-KD are labeled in blue, downregulated genes are in red. Nanog, Rex1 and Actin B (ActB) are shown as genes not regulated by BAZ2A. mRNA levels were normalized to Rps12 mRNA and to ESCs transfected with siRNA-Control. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns: non significant, * < 0.05, ** < 0.01, *** < 0.001, **** < 0.0001).",
    "ncbi_link": "Actin B: 11461
ActB: 11461
BAZ2A: 116848
Nanog: 71950
Rex1: 66932
Rps12: 20042
TOP2A: 21973"
  },
  {
    "caption": "E. Inhibition of type 2 topoisomerase activity phenocopies the alterations in gene expression of BAZ2A-regulated genes in ESC+2i observed upon TOP2A or BAZ2A knockdown. ESCs were treated with the TOP2 inhibitor ICF-193 for 24 hours. mRNA levels were normalized to Rps12 mRNA and to ESCs treated with DMSO. Upregulated genes in ESC+2i upon BAZ2A-KD are labeled in blue, downregulated genes are in red. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns: non significant, ** < 0.01, *** < 0.001, **** < 0.0001).",
    "ncbi_link": "BAZ2A: 116848
Rps12: 20042
TOP2A: 21973"
  },
  {
    "caption": "F. ChIP analysis showing that TOP2A regulates H3K27me3 occupancy in ESC+2i but not in ESC+serum. Data were measured by qPCR and normalized to input and to Tshz1 value in cells transfected with siRNA-control. #1-#4 indicated sequences with elevated H3K27me3 at CTCF boundary (H3K27me3hi/CTCF). Control represents an intergenic region that does not contain H3K27me3. Average values of three independent experiments. Error bars represent s.d. Statistical significance (P-values) for the experiments was calculated using the paired two-tailed t-test (ns: non significant, * < 0.05, ** < 0.01, *** < 0.001).",
    "ncbi_link": "CTCF: 13018
TOP2A: 21973
Tshz1: 110796"
  },
  {
    "caption": "C Infiltration of leaves with 37 nM GRIp31-96 induced elevated ion leakage in Col‐0 and prk4, but not in prk5‐1 or prk5‐2. Infiltration with GST caused the same background effect for all lines.",
    "ncbi_link": "prk5: 841483
prk4: 821563"
  },
  {
    "caption": "D Genomic complementation of prk5 rescues the insensitivity to induction of elevated ion leakage by GRIp31-96.",
    "ncbi_link": "prk5: 841483"
  },
  {
    "caption": "E Enzymatic superoxide production from xanthine/xanthine oxidase (XXO) induced more electrolyte leakage in gri compared to Col‐0 or prk5‐1, prk5‐2 and prk4 after infiltration into leaves. Infiltration with xanthine buffer (X) was used as a control.",
    "ncbi_link": "prk5: 841483
prk4: 821563
gri: 841747"
  },
  {
    "caption": "H Kinase activity of PRK5 in in vitro phosphorylation assays using γ32P‐ATP and myelin‐basic protein (MBP) as a substrate in the presence of 10 mM MnCl2. GST‐PRK5 and GST‐PRK4 did not show kinase activity. Mutation of conserved residues in kinase subdomains VIb and VII to reconstitute the consensus kinase domain motif restored GST‐PRK5H500DA520G kinase activity. GST‐CRK7 was used as a positive control. Upper panel shows autoradiograph, and lower panel shows the Coomassie‐stained 15% SDS-polyacrylamide gel.",
    "ncbi_link": "PRK5: 841483"
  },
  {
    "caption": "B Infiltration of 37 nM GST, GRIp31-96, GRIp65-84 or Y‐GRIp65-84 into Col‐0 or prk5‐2 leaves. Tyrosine‐labeled GRIp65-84 still induced cell death in Col‐0 but not in prk5‐2 plants.",
    "ncbi_link": "prk5: 841483"
  },
  {
    "caption": "C 125I‐labeled Y‐GRIp65-84 (0.46 nM) bound specifically to Col‐0membrane fractions (light gray bars), the binding was significantly reduced in prk5 plants. Excess of non‐radioactive Y‐GRIp65-84 (10 μM) reduced binding to background levels (dark gray bars; all bars show the average of three samples, triangles show individual data points).",
    "ncbi_link": "prk5: 841483"
  },
  {
    "caption": "E Binding of 125I‐Y‐GRIp65-84 (0.46 nM) to immunoprecipitates (using anti‐c‐myc antibodies) from prk5‐2 protoplasts transfected with PRK5‐c‐myc, PRK4‐c‐myc or YFP, respectively. Binding was competed out with 10 μM unlabeled Y‐GRIp65-84. Bars show the average of two samples, and triangles show individual data points. Western blot is shown in panel (D).",
    "ncbi_link": "prk5: 841483"
  },
  {
    "caption": "A Recombinant AtMC9 (rAtMC9) cleaved GRI25-168in vitro. Bacterially produced MBP‐GRI25-168 (from 0 to 2 pmol left to right) was incubated with 1 pmol rAtMC9 or inactive rAtMC9mut (rAtMC9C147AC29A), and cleavage products were analyzed by Western blot with anti‐MBP and anti‐AtMC9 antibodies. Arrowheads in the anti‐MBP blot (from top to bottom) indicate MBP‐GRI25-168 (63.5 kDa), MBPMCS (53.5 kDa), rAtMC9‐cleaved MBP‐GRI25-168 (46 kDa). Arrowheads in the anti‐AtMC9 blot indicate: 1: N‐terminal domain + p20 + p10 subunits of AtMC9, 2: p20 + p10 subunits of AtMC9, 3: N‐terminal domain + p20 subunit of AtMC9, 4: p20 subunit of AtMC9.",
    "ncbi_link": "GRI: 841747
MC9: 830299"
  },
  {
    "caption": "B Infiltration of wild‐type, prk5‐1 and atmc9‐1 leaves with 37 nM GRIp31-96, GRIp65-84, GRIp68-78 or GST. GRIp65-84 and GRIp68-78 but not GRIp31-96 were able to induce elevated ion leakage in the atmc9‐1 mutant.",
    "ncbi_link": "prk5: 841483
mc9: 830299"
  },
  {
    "caption": "E 125I‐labeled Y‐GRIp68-78 (0.46 nM) bound specifically to Col‐0membrane fractions (light gray bars), the binding was significantly reduced in prk5‐1 and prk5‐2 plants. Excess of non‐radioactive Y‐GRIp65-84 (10 μM) reduced binding to background levels (dark gray bars; all bars show the average of four samples, triangles show individual data points).",
    "ncbi_link": "prk5: 841483"
  },
  {
    "caption": "(A) Histogram (mean, 95 %CI) of fold induction of PXR activity reporter assay (luc, luciferase) in LS180 cells transiently transfected with wild-type PXR and p3A4-luc reporter plasmids. Chemical structures of FKK5, FKK6 and FKK999 compounds are overlaid. The bar graph(s) depicts one representative experiment of a series of experiments (n > 3) performed in four consecutive passages of cells. *p < 0.05, one-way ANOVA with Dunnett's post hoc test. *significant over vehicle (DMSO) control.",
    "ncbi_link": "luc: 
p3A4: 1576
PXR: 8856"
  },
  {
    "caption": "(B), same as (A), in HepG2 cells stably expressing pCYP1A1 luciferase plasmid (AhR reporter). Chemical structures of FKK5, FKK6 and FKK999 compounds are overlaid. Indole is colored blue. The bar graph(s) depicts one representative experiment of a series of experiments (n > 3) performed in four consecutive passages of cells. *p < 0.05, one-way ANOVA with Dunnett's post hoc test. *significant over vehicle (DMSO) control.",
    "ncbi_link": "luciferase: 
pCYP1A1: 13076"
  },
  {
    "caption": "C, Histogram (mean, 95 %CI) of fold mRNA expression, CYP1A1 (top panel), CYP3A4 (middle panel) and MDR1 (bottom panel) in LS180 cells with or without (mock) transfected PXR plasmid, HepaRG hepatic progenitor cells (PXR-knockout, PXR-KO; AhR-knockout, AhR-KO; parental control 5F clone) and primary human hepatocytes (HEP) from four donors is shown. The bar graph represents one experiment of a series of experiments (n > 3) performed in four consecutive passages of LS180 cells; n = 2 independent experiments with one well/compound and RT-PCR performed in triplicate for each HepaRG genotype; for each donor hepatocyte, n = 1 well/compound and RT-PCR performed in triplicate. *, #p < 0.05, two-way ANOVA with Tukey's post hoc test. *significant over vehicle control. #significant over the same treatment in corresponding mock transfected or knock-out cells.",
    "ncbi_link": "MDR1: 5243
AhR: 196
CYP1A1: 1543
CYP3A4: 1576
PXR: 8856"
  },
  {
    "caption": "D, Chromatin Immunoprecipitation (ChIP) assay in LS174T cells. Top panel, PCR products cells exposed to vehicle or FKK6 and run on a 2% agarose gel. DNA 100 base pair marker; Vehicle,10% DMSO; FKK6 (10 μM); 1/10 Input - 0.2 million cells before IP; IgG - IP with polyclonal rabbit IgG; PXR - IP with PXR antibody. Bottom panel, quantitative PCR from the ChIP assay for compounds tested with the gene specific PCR amplicon normalized to GAPDH (fold expression). Dash line, 2-fold expression. The data is one representative experiment of two independent experiments (each n = 3 biological replicates, n = 4 technical replicates). Mean fold expression is expressed above each histogram (mean + SD).",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "A, PXR (luciferase) reporter assay in HEK293T cells transiently transfected with PXR plasmids (wild-type and ligand binding domain mutant C285I/C301A). RLU, relative light units are shown normalized to beta-galactosidase (β-Gal) expression. The histogram represents one experimental data (of n > 2 independent experiments each performed in quadruplicate) mean (95 %CI); n.s. not significant; * p < 0.05, two-way ANOVA.",
    "ncbi_link": "beta-galactosidase: 2720
β-Gal: 2720
PXR: 8856"
  },
  {
    "caption": "B, Histogram represents fold change in mRNA expression, normalized to GAPDH, by RT-qPCR from Caco-2 cells exposed to compounds. DMSO, 0.1% DMSO vehicle; 9.3 is 9.3-fold expression. The data is one representative experiment of two independent experiments (each n = 3 biologic replicates, n = 4 technical replicates).",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "E, LS174T PXR-KO (knockout) cells transiently transfected with pNL3.2.NF-κB-RE vector. mean (+ SD). *, ** p < 0.05, two way ANOVA with Tukey's multiple comparisons test.",
    "ncbi_link": "PXR: 8856"
  },
  {
    "caption": "A In Caco-2 monolayer cells, Log10 relative expression of IL8 mRNA with or without cytokines (50 ng/ml IL-1, 10 ng/ml IFNγ, 10 ng/ml TNF α), and cytokine cocktail plus FKK drugs (10 and 25 μM) with 2 h or 12 h incubations.",
    "ncbi_link": "IL8: 3576"
  },
  {
    "caption": "Log10 relative expression of IL8 mRNA with or without cytokines (50 ng/ml IL-1, 10 ng/ml IFNγ, 10 ng/ml TNF α), and cytokine cocktail plus FKK drugs (10 and 25 μM) with 2 h or 12 h incubations. In human intestinal organoids (HIO),",
    "ncbi_link": "IL8: 3576"
  },
  {
    "caption": "Quantitative gene expression by RT-qPCR of IL8 mRNA from human colonic enteroids (over 40 enteroids per individual sample per well) exposed to control (vehicle) or TNF α. with or without FKK5 (n = 9 paired samples). Data shown as mean fold change relative to vehicle control (con) for each paired sample (n = 3 replicates). Each paired sample data set represents biopsies from an individual patient. *, ## p < 0.05, Pair-wise one way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "IL8: 3576"
  },
  {
    "caption": "Quantitative gene expression by RT-qPCR of IL8 mRNA from human colonic enteroids (over 40 enteroids per individual sample per well) exposed to control (vehicle) or TNF α. with or without FKK6 (n = 3 paired samples; one removed due to poor inflammatory response). Data shown as mean fold change relative to vehicle control (con) for each paired sample (n = 3 replicates). Each paired sample data set represents biopsies from an individual patient. *, ## p < 0.05, Pair-wise one way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "IL8: 3576"
  },
  {
    "caption": "Quantitative gene expression by RT-qPCR of IL8 mRNA from human colonic enteroids (over 40 enteroids per individual sample per well) exposed to control (vehicle) or TNF α. with or without FKK9 (n = 5; 3 removed due to poor response and tissue integrity). Data shown as mean fold change relative to vehicle control (con) for each paired sample (n = 3 replicates). Each paired sample data set represents biopsies from an individual patient. *, ## p < 0.05, Pair-wise one way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "IL8: 3576"
  },
  {
    "caption": "Fold induction (mRNA) of genes in C57BL/6 mice gavaged with vehicle (10% DMSO; n = 3) or FKK6 (500 μM in 10% DMSO; n = 3) every 12h for 3 total doses. The entire experiment was repeated two independent times and one representative experiment is shown. Each mouse (each organ) was studied in quadruplicate assays and normalized to internal control, GAPDH. The histograms show mean (95% CI) values for gene expression. The dotted line marks basal fold expression",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "Fold induction (mRNA) of genes in pxr -/- mice gavaged with vehicle (10% DMSO; n = 3) or FKK6 (500 μM in 10% DMSO; n = 3) every 12h for 3 total doses. The entire experiment was repeated two independent times and one representative experiment is shown. Each mouse (each organ) was studied in quadruplicate assays and normalized to internal control, GAPDH. The histograms show mean (95% CI) values for gene expression. The dotted line marks basal fold expression",
    "ncbi_link": "GAPDH: 14433
pxr: 18171"
  },
  {
    "caption": "Fold induction (mRNA) of genes in hPXR mice (mice expressing the human PXR gene) gavaged with vehicle (10% DMSO; n = 3) or FKK6 (500 μM in 10% DMSO; n = 3) every 12h for 3 total doses. The entire experiment was repeated two independent times and one representative experiment is shown. Each mouse (each organ) was studied in quadruplicate assays and normalized to internal control, GAPDH. The histograms show mean (95% CI) values for gene expression. The dotted line marks 2-fold gene induction.",
    "ncbi_link": "GAPDH: 14433
hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. A, % weight loss from baseline (day 1 vs day 10)",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. B, colon length (cm)",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. C, Inflammation score",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. D, Fecal lipocalin 2 (pg/ml)",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. E, serum FITC-dextran (μg/ml).",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "After coin-toss randomization, hPXR mice (mice expressing the human PXR gene) were allocated to treatment with vehicle (0.8% DMSO) (n = 3/genotype) or FKK6 (200 micromolar) (n = 3/genotype), by simultaneous oral gavage and intra-rectal delivery starting day 1 - 10 of DSS administration. F, fold expression of mRNA as illustrated in hPXR mouse colon tissue exposed to DSS (n = 3/group; each PCR performed in quadruplicate).",
    "ncbi_link": "hPXR: 8856
PXR: 8856"
  },
  {
    "caption": "As in Fig 5, pxr -/- mice underwent the identical experimental procedure and analysis. The entire experiment was repeated three independent times and one representative experiment is shown.",
    "ncbi_link": "pxr: 18171"
  },
  {
    "caption": "As in Fig 5, pxr -/- mice underwent the identical experimental procedure and analysis. The entire experiment was repeated three independent times and one representative experiment is shown.",
    "ncbi_link": "pxr: 18171"
  },
  {
    "caption": "As in Fig 5, pxr -/- mice underwent the identical experimental procedure and analysis. The entire experiment was repeated three independent times and one representative experiment is shown.",
    "ncbi_link": "pxr: 18171"
  },
  {
    "caption": "As in Fig 5, pxr -/- mice underwent the identical experimental procedure and analysis. The entire experiment was repeated three independent times and one representative experiment is shown.",
    "ncbi_link": "pxr: 18171"
  },
  {
    "caption": "As in Fig 5, pxr -/- mice underwent the identical experimental procedure and analysis. The entire experiment was repeated three independent times and one representative experiment is shown.",
    "ncbi_link": "pxr: 18171"
  },
  {
    "caption": "(B) NSC-34 and SH-SY5Y cells were transfected with various concentrations of siPRPH or siNTC. The efficiency of siRNA knockdown at 48h.p.t. was validated by Western blot while cytotoxicity was determined by AlamarBlue assay. siPRPH- or siNTC-transfected cells were infected with EV-A71 S41, and the viral titers were determined at 48h.p.i.",
    "ncbi_link": "PRPH: 5630
PRPH: 19132"
  },
  {
    "caption": "(A) NSC-34 and SH-SY5Y cells were reverse-transfected with siPRPH or siNTC for 48 hrs prior to transfection with EV-A71 RNA. The culture supernatants were harvested for viral titer determination at 24h.p.t.",
    "ncbi_link": "PRPH: 5630"
  },
  {
    "caption": "A) oxLDL plasma concentration in ACM patients and HC (n=36; Mann-Whitney test). B) oxLDL plasma concentration in mutated ACM (n=7) and NON ACM relatives, carriers of the same causative mutation (n=9; Mann-Whitney test). C)  oxLDL plasma concentration in ACM patients carriers of a  PKP2 mutation and ACM patients carriers of other desmosomal or non desmosomal mutations, or gene elusive (n=10 vs. n=26; One-Way ANOVA). Data information: mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "PKP2: 5318"
  },
  {
    "caption": "D) Left panel: representative images of internalization  of  oxLDL (red) in ACM C-MSC  treated with scramble siRNA or CD36 siRNA, cultured in  AM  and subjected to 10μg/ml  DiI oxLDL treatment. Right panel: quantification of the  DiI fluorescence normalized on  nuclei number (n=3 biological replicates, arbitrary units; Two-tailed Student's t-test). Data information: mean ± SEM. * p<0.05; ** p<0.01.",
    "ncbi_link": "CD36: 948"
  },
  {
    "caption": "C) Left panels: representative images of ORO staining  of  HFD-fed WT and Pkp2+/-   cardiac sections. Right panel: quantification of ORO positive area percentage (n=10). For comparison, quantification of ORO positive area of cardiac sections of  CD-fed WT and Pkp2+/- mice (n=9; Two-Way Anova) is shown (Appendix Figure S3). D) Representative images of  PPARγ  (green) immunostaining on  HFD-fed WT and  Pkp2+/- mice cardiac sections (n=10; Two-Way Anova). Quantification of the PPARγ staining in HFD is shown relative to the values of CD (n=9). E) Representative images of MDA (green)  immunostaining  on  HFD-fed WT and Pkp2+/- mice cardiac  sections (n=10; Two-Way Anova). Quantification of the  MDA staining  in HFD is shown relative to the values of  CD  (n=9). F) Representative images of CD36 immunostaining (green) on HFD-fed WT and Pkp2+/-  mice cardiac sections (n=10; Two-Way Anova). Nuclei  are counterstained with Hoechst33342 (blue). Quantification of the staining  in HFD  is shown relative to the values of CD  (n=9). Data information: mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "Pkp2: 67451"
  },
  {
    "caption": "C) Left panel: representative images of ORO staining of cardiac sections  of Pkp2+/- mice, fed a 3-month HFD plus atorvastatin. Right panel: quantification of the percentage of ORO positive area (n=9) is compared to that in HFD (as in Figure 6C; Two-tailed Student's t-test). D) Representative images of  PPARγ immunostaining (green) on  cardiac  sections of Pkp2+/- mice fed a 3-month  HFD plus atorvastatin  (n=9). Quantification is compared to the values of Pkp2+/- in HFD and relative to WT in CD (as in Figure 6D; Two-tailed Student's t-test). E) Representative images of MDA immunostaining (green) on  cardiac  sections  of Pkp2+/- mice fed a 3-month HFD  plus atorvastatin (n=9). Quantification is compared to the values of Pkp2+/- in  HFD  and relative to WT in CD (as in Figure 6E; Two-tailed Student's t-test). F) Representative images of CD36 immunostaining (green) on cardiac sections of Pkp2+/-  mice  fed a 3-month HFD plus atorvastatin (n=9). Quantification is compared to the values of Pkp2+/- HFD  and relative to WT in  CD (as in Figure 6F; Two-tailed Student's t-test). Nuclei  are counterstained  with  Hoechst33342  (blue). Data information: mean ± SEM. * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "Pkp2: 67451"
  },
  {
    "caption": "RT-qPCR of Abca1 transcripts following 1 μM T0901317 stimulation of LXR+/+ and LXR−/− primary BMMs. Fold changes are shown relative to LXR+/+ 0 h. Error bars represent ± SEM for n = 4-8 (**P = 0.001 at 8 h and **P = 0.00004 at 16 h versus LXR−/−; **P = 0.0003 at 0 h versus LXR+/+); bottom, proposed model explaining the ligand‐dependent induction of Abca1. Following ligand stimulation, LXR-corepressor complexes are exchanged for LXR-coactivator complexes, which promote gene expression. The LXR-cofactor interactions responsible for the attenuation of expression beginning after 16 h remain unknown.",
    "ncbi_link": "Abca1: 11303
LXR: 22259"
  },
  {
    "caption": "Luciferase reporter assays from RAW 264.7 macrophages expressing reporter alone, or together with full‐length SND1, SART1, or HMBOX1. LXR ligand stimulations with 1 μM T0901317 were performed for 18 h. A diagram of the reporter construct is shown above. Fold changes are shown relative to vehicle‐stimulated reporter alone (first lane). Error bars represent ± SEM for n = 9 (**P = 0.001, *P = 0.011 for SND1, *P = 0.046 for SART1).",
    "ncbi_link": "HMBOX1: 219150
LXR: 22259
SART1: 20227
SND1: 56463"
  },
  {
    "caption": "Luciferase reporter assays from RAW 264.7 macrophages expressing reporter alone, or together with full‐length NCOA5 or an NCOA5 mutant lacking the NH2‐terminus. LXR ligand stimulations with 1 μM T0901317 were performed for 18 h. Diagrams of the reporter constructs are shown above. Fold changes are shown relative to vehicle‐stimulated reporter alone (first lane). Error bars represent ± SEM for n = 6-12 (**P 0.001, *P = 0.035).",
    "ncbi_link": "NCOA5: 228869
LXR: 22259"
  },
  {
    "caption": "RT-qPCR of Abca1 transcripts following infection of primary BMMs with Ncoa5 or control retrovirus. LXR ligand stimulations were performed with 1 μM T0901317 for 18 h. Fold changes are shown relative to vehicle‐stimulated control. Error bars represent ± SEM for n = 4 (*P = 0.029).",
    "ncbi_link": "Abca1: 11303
Ncoa5: 228869
LXR: 22259"
  },
  {
    "caption": "In vitro pulldown assays using recombinant GST‐LXRα to isolate the indicated in vitro translated NCOA5 constructs. Assays were performed for 2 h in the presence or absence of 2 μM T0901317. Samples were immunoblotted as indicated. Note the requirement of the NCOA5 NH2‐terminus for interacting with LXRα.",
    "ncbi_link": "NCOA5: 228869
LXRα: 22259"
  },
  {
    "caption": "Immunoprecipitation of Protein C‐tagged LXRα from stable RAW 264.7macrophagenuclear extracts stimulated with 1 μM T0901317 or vehicle control for 18 h, followed by immunoblotting for endogenous NCOA5 or over‐expressed LXRα. Protein immunoblots of nuclear extracts are shown below.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "NCOA5 ChIP time course from primary BMMs stimulated with 1 μM T0901317 or vehicle control. qPCR was performed for the Abca1 proximal LXRE. Note the ligand‐stimulated association of NCOA5. Error bars represent ± SEM for n = 4-9 (*P = 0.02).",
    "ncbi_link": "Abca1: 11303
NCOA5: 228869"
  },
  {
    "caption": "NCOA5 ChIP assays from LXR−/− BMMs stimulated with 1 μM T0901317 or vehicle control for 18 h. qPCR was performed for the Abca1 proximal LXRE. Error bars represent ± SEM for n = 5-6 (**P = 0.0003 for vehicle and **P = 0.002 for T0901317).",
    "ncbi_link": "Abca1: 11303
NCOA5: 228869
LXR: 22259"
  },
  {
    "caption": "RT-qPCR of Abca1 expression following 1 μM T0901317 treatment in primary BMMs infected with a non‐silencing or Ncoa5‐specific shRNA. Fold changes are shown relative to shControl 0 h. Note the elevated Abca1 expression at 24-30 h following loss of NCOA5. Error bars represent ± SEM for n = 4-6 (**P = 0.0007 at 24 h and **P = 0.004 at 30 h, *P = 0.02).",
    "ncbi_link": "Abca1: 11303
Ncoa5: 228869
NCOA5: 228869"
  },
  {
    "caption": "Quantification of ABCA1 immunoblots from primary BMMs infected as in (A). Representative immunoblot is shown in Supplementary Fig S7E. LXR ligand stimulation with 1 μM T0901317 or vehicle control was performed for 8 h or 30 h. Error bars represent ± SEM for n = 2 (**P = 0.007).",
    "ncbi_link": "LXR: 22259"
  },
  {
    "caption": "A, B RT-qPCR of Abca1 expression from primary BMMs infected with non‐silencing or Ncoa5‐specific shRNAs. Ligand stimulations were performed for 4 h with vehicle control, 1 μM T0901317 alone or together with 6 μg/ml PolyIC (A) or 10 ng/ml LPS (B). Fold changes are shown relative to vehicle‐stimulated shControl. Note only the loss of TLR3‐mediated repression following Ncoa5 silencing. Error bars represent ± SEM for n = 4-10 (**P = 0.0003 for A, **P = 0.0004 for shControl in B, **P = 0.0002 for shNcoa5 in B versus T0901317).",
    "ncbi_link": "Abca1: 11303
Ncoa5: 228869"
  },
  {
    "caption": "C, D RT-qPCR of Abca1 expression from primary BMMs infected with non‐silencing or Ncoa5‐specific shRNAs. Ligand stimulations were performed for 4 h unstimulated, or with 6 μg/ml PolyIC (C) or 10 ng/ml LPS (D). Fold changes are shown relative to unstimulated shControl. Error bars represent ± SEM for n = 4-6 (**P = 0.0006 for C, **P = 0.00000001 for shControl in D, **P = 0.000001 for shNcoa5 in D, *P = 0.013 versus T0901317).",
    "ncbi_link": "Abca1: 11303
Ncoa5: 228869"
  },
  {
    "caption": "E NCOA5 ChIP assays from primary BMMs stimulated for 3 h with 1 μM T0901317, 1 μM T0901317 + 6 μg/ml PolyIC, or vehicle control. qPCR was performed for the Abca1 proximal LXRE. Note the increased occupancy only in the presence of both lipid and inflammatory ligands. Error bars represent ± SEM for n = 8-12 (**P = 0.0007 versus T0901317).",
    "ncbi_link": "Abca1: 11303
NCOA5: 228869"
  },
  {
    "caption": "F NCOA5 ChIP assays from primary BMMs stimulated for 3 h with 6 μg/ml PolyIC or left unstimulated. qPCR was performed for the Abca1 proximal LXRE. Error bars represent ± SEM for n = 5-6.",
    "ncbi_link": "Abca1: 11303
NCOA5: 228869"
  },
  {
    "caption": "G Cholesterol efflux assays to APOA1 from primary BMMs infected with non‐silencing or Ncoa5‐specific shRNAs. Agonist stimulations were performed for 6 h. Error bars represent ± SEM for n = 3 (*P = 0.02 versus T0901317).",
    "ncbi_link": "Ncoa5: 228869"
  },
  {
    "caption": "A, B Unmodified/pSer5 RNAPII (A) or RNAPII pSer2 (B) ChIP assays from primary BMMs stimulated for 4 h with 1 μM T0901317, 1 μM T0901317 + 6 μg/ml PolyIC, or vehicle control. qPCR was performed for the Abca1 TSS. Error bars represent ± SEM for n = 6-9 (**P = 0.0001 in A, **P = 0.002 in B versus T0901317).",
    "ncbi_link": "Abca1: 11303"
  },
  {
    "caption": "C, D RNAPII ChIP assays as in (A, B) but performed from LXR−/− BMMs. Error bars represent ± SEM for n = 5-9 (**P = 0.000000001, *P = 0.02 versus T0901317).",
    "ncbi_link": "LXR: 22259"
  },
  {
    "caption": "E RT-qPCR of Abca1 expression from LXR+/+ versus LXR−/− BMMs. Ligand stimulations were performed for 4 h with vehicle control, 1 μM T0901317, or 1 μM T0901317 together with 6 μg/ml PolyIC. Fold changes are shown relative to vehicle‐stimulated LXR+/+. Error bars represent ± SEM for n = 4 (**P = 0.004, *P = 0.012 versus T0901317).",
    "ncbi_link": "Abca1: 11303
LXR: 22259"
  },
  {
    "caption": "F RNAPII pSer2 ChIP assays from primary BMMs infected with non‐silencing or Ncoa5‐specific shRNAs. Ligand stimulations were performed for 4 h with vehicle control, 1 μM T0901317, or 1 μM T0901317 + 6 μg/ml PolyIC. qPCR was performed for the Abca1 TSS. Note RNAPII pSer2 returns to baseline occupancy following TLR3 stimulation in shControl but not shNcoa5 BMMs (**P = 0.004 versus baseline). Error bars represent ± SEM for n = 3 from 11 mice.",
    "ncbi_link": "Abca1: 11303
Ncoa5: 228869"
  },
  {
    "caption": "A) H&E and immunohistochemistry reveal that β-catenin accumulates in tumors emerging in one-year-old female miR-424(322)/503-/- mice. The panel is a representative image of n=5 independent tumors. The scale bar indicates 100 micrometers (µM).",
    "ncbi_link": "miR-424: "
  },
  {
    "caption": "B) Bar graphic showing that human breast cancers with deletion of the miR-424/503 locus have higher protein levels of β-catenin (RPPA). P-value is calculated based on one-sided Wilcoxon rank-sum test. In the box-plots in B and C the relative expression of β-catenin in the RPPA data from TCGA is shown. The yellow line indicates the median and the bars indicate the 75th percentile (Q3)+1.5 interquartile range (IQR).",
    "ncbi_link": "miR-424: 494336"
  },
  {
    "caption": "C) The bar graph shows that human breast cancers with low expression levels of miR-424 and miR-503 have higher protein levels of β-catenin. P-value is calculated based on one-sided Wilcoxon rank-sum test.",
    "ncbi_link": "miR-424: 494336
miR-503: 574506"
  },
  {
    "caption": "B) The bar graphs show the number of PROCR+ in 1-year-old female WT and miR-424(322)/503 KO mice during diestrus. The error bars show the standard deviation.",
    "ncbi_link": "miR-424: "
  },
  {
    "caption": "D) Western blot of LRP6 and TBLR1 in the miR-cluster-Dox-MCF-10A model upon upregulation of miR-cluster with 100 ng/ml of doxycycline for the specified number of days. The numbers below the blots indicate the quantitation by densitometry of protein expression relative to β-actin. The expression level of miR-424 and miR-503 is indicated in the bar graph below the blots. UN indicates samples untreated with doxycycline. The error bars show the standard deviation.",
    "ncbi_link": "miR-424: 494336
miR-503: 574506"
  },
  {
    "caption": "F) Western blot of LRP6 and TBLR1 expression in WT and miR-424/503-KO basal cell-derived organoids after 14 days in culture with and without Wnt3a (100ng/ml). The arrow shows the correct TBLR1 band.",
    "ncbi_link": "miR-424: "
  },
  {
    "caption": "G) IHC staining showing that LRP6 accumulates in the epithelium of female miR-424(322)/503-/- mice (1-year-old). The scale bar indicates 100 micrometers (µM).",
    "ncbi_link": "miR-424: "
  },
  {
    "caption": "A) Enrichment of the putative LRP6 binding sites bound to AGO2 in miR-cluster-Dox-MCF-10A cells after the miR-424/503 cluster is induced with 100ng/ml of dox for three days. A CDC25A-binding site is included as a positive control and a region of B2M and GAPDH are included as negative controls. The error bars show the standard deviation.",
    "ncbi_link": "B2M: 567
CDC25A: 993
GAPDH: 2597
LRP6: 4040
miR-424: 494336"
  },
  {
    "caption": "B) The WT-blot shows the expression of LRP6 upon upregulation of miR-424/503 in miR-cluster-Dox-MCF-10A cells (Dox+) when one or both of the conserved microRNA binding sites (#1 and #3) are blocked by target protection.",
    "ncbi_link": "miR-424: 494336"
  },
  {
    "caption": "(B) Real‐time PCR analysis of human BAG family members and Hsc70 and Hsp90 in young and old I90 cells. Depicted is the expression ratio (log2) of target genes in old cells relative to young cells. *P0.05 and **P0.01 versus young, n=3.",
    "ncbi_link": "Hsp90: 3320
Hsc70: 3312///10722"
  },
  {
    "caption": "(A) 293 cells were transfected with bag1, bag3 or nonsense (nons) siRNAs, as indicated. After 48 h, cells were transfected with d2GFP expression plasmid together with half the amounts of the indicated siRNAs. After additional 24 h, levels of indicated proteins were detected by immunoblot analysis.",
    "ncbi_link": "bag1: 573
bag3: 9531"
  },
  {
    "caption": "(B) 293 cells were transfected with indicated siRNAs for 48 h followed by real‐time PCR analysis of BAG1 and BAG3 mRNA levels. Depicted is the mean relative expression ratio (log2) ±s.e.m. *P0.05 and ***P0.001 versus nons, n=3.",
    "ncbi_link": "BAG1: 573
BAG3: 9531"
  },
  {
    "caption": "(C) BAG1 knockdown was performed in 293 cells for 48 h. Thereafter, cells were transfected with GFP or GFP‐based UPS reporter genes as indicated. After additional 24 h, levels of GFP‐positive proteins were detected by western‐blot analysis using a GFP antibody.",
    "ncbi_link": "BAG1: 573"
  },
  {
    "caption": "(A) 293 cells were transfected with nonsense (nons), bag1 or bag3 siRNAs for 48 h and then treated for 2 h with the lysosomal inhibitors pepstatinA and E64 (both 10 μg/ml; Pep.A/E64) or DMSO as control, followed by immunoblot analysis of the indicated proteins.",
    "ncbi_link": "bag1: 573
bag3: 9531"
  },
  {
    "caption": "(B) 293 cells were transfected for 48 h with the indicated siRNAs and BAG3 expression plasmid (BAG3‐N1) or vector control (N1) followed by the same analysis as in (A).",
    "ncbi_link": "N1: 
BAG3: 9531"
  },
  {
    "caption": "(C) Diagram shows the autophagic flux of 293 cells with differently modulated BAG1 and BAG3 levels as described in (A) and (B). Autophagic flux was determined by the strength of LC3‐II accumulation in a 2‐h treatment period with Pep.A/E64. Therefore, normalised LC3‐II levels in the absence of inhibitors were subtracted from corresponding levels obtained in the presence of Pep.A/E64. Values are expressed as mean±s.e.m. *P0.05 versus control‐transfected cells, n=3.",
    "ncbi_link": "BAG1: 573
BAG3: 9531"
  },
  {
    "caption": "(D) I90 cells were transfected with GFP fused to LC3 (pGFP.LC3) and co‐transfected either with BAG3‐N1 or N1. After transfection for 48 h, cells were treated as in (A) and levels of indicated proteins were detected by immunoblot analysis.",
    "ncbi_link": "BAG3: 9531
LC3: 84557"
  },
  {
    "caption": "(E) I90 cells, transfected as in (D) for 24 h, were microscopically analysed for GFP‐LC3 fluorescence. Representative pictures are shown. Bar: 20 μm. Values expressed in diagram are mean±s.e.m. from three independent experiments (50 cells were counted per experiment). *P0.05 versus N1, n=3.",
    "ncbi_link": "LC3: 84557"
  },
  {
    "caption": "(A) I90 cells were transfected with BAG3 (BAG3‐N1) or vector control. After transfection for 48 h, levels of indicated proteins were detected by western‐blot analysis.",
    "ncbi_link": "BAG3: 9531"
  },
  {
    "caption": "(B) Transcript levels of SQSTM1 in I90 cells transfected as in (A) were compared by real‐time PCR analysis. Depicted is the fold‐increase of SQSTM1 mRNA levels in BAG3‐N1‐transfected cells relative to control (N1)‐transfected cells. Values are expressed as mean±s.e.m. **P0.01 versus N1 cells, n=3.",
    "ncbi_link": "BAG3: 9531
SQSTM1: 8878"
  },
  {
    "caption": "(C) I90 cells were transfected with a BAG3‐GFP fusion plasmid for 48 h followed by indirect immunofluorescence staining of endogenous SQSTM1. (a) Direct fluorescence of BAG3‐GFP (green), (b) indirect immunofluorescence of SQSTM1 (red) and (c) the stainings of (a) and (b) overlapped. DAPI (blue) was used to stain DNA. Representative pictures are shown. Bar: 10 μm.",
    "ncbi_link": "BAG3: 9531"
  },
  {
    "caption": "(B) Real‐time PCR analysis of LC3, WIPI1 and SQSTM1 mRNA levels in young and old I90 cells. Depicted is the mean expression ratio (log2) ±s.e.m. of target genes in old cells relative to young cells. **P0.01 and ***P0.001 versus young, n=3.",
    "ncbi_link": "LC3: 84557
SQSTM1: 8878
WIPI1: 55062"
  },
  {
    "caption": "(H) I90 cells of old (upper panel) and young (lower panel) age were transfected with atg7 or nonsense (nons) siRNA. After transfection for 4 days , the cells were treated with NH4Cl/Leu or DMSO for 1 h followed by fractioning of cell lysates in TritonX‐100 (TX‐100) soluble and insoluble material. Equal protein amounts of both fractions were directed to immunoblot analysis for analysis of indicated proteins. Gapdh and Histone H3 were used as loading controls of soluble and insoluble fractions, respectively.",
    "ncbi_link": "atg7: 10533"
  },
  {
    "caption": "(B, C) After transfection for 96 h of old I90 cells with bag3 or nonsense (nons) siRNA, BAG1 and BAG3 protein and mRNA levels were analysed by immunoblot (B) and real‐time PCR (C) analysis, respectively. Transcript levels in bag3 siRNA cells are depicted as the mean log2 expression ratio ±s.e.m. relative to nons siRNA cells. *P0.05 and ***P0.001 versus nons, n=3.",
    "ncbi_link": "bag3: 9531"
  },
  {
    "caption": "(D) Indirect immunofluorescence analysis of endogenous LC3 (green) and WIPI1 (white) in old I90 cells transfected with nons (a, b) and bag3 siRNA (c, d) for 96 h. DAPI (blue) was used as a nuclear marker. Representative pictures are shown. Bar: 20 μm. Diagrams show percentage of cells counted as in Figure 3E.",
    "ncbi_link": "bag3: 9531"
  },
  {
    "caption": "(G, H) Same analysis as in (F) but young I90 cells 48 h after transfection with a BAG3 expression plasmid (BAG3‐N1) or vector control (N1) together with nons or sqstm1 siRNA (G) and nons or atg7 siRNA (H), as indicated, were used. *, #, ∼ and +, P0.05 versus C N1, C BAG3‐N1, C BAG3‐N1 sqstm1 or atg7 and C N1 sqstm1 or atg7, n=3.",
    "ncbi_link": "atg7: 10533
BAG3: 9531
sqstm1: 8878"
  },
  {
    "caption": "(A) WT or Mfn2 KO MEFs (Mfn2 KO cells) were treated with 1 μM Tg for 12 h and then processed for EM visualization of the ER morphology. Scale bar: 1 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(B) EM images of Tg‐treated Mfn2 KO cells show accumulation of ER membrane stacking. Scale bar: 1 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(C) WT, Mfn2 KO or Mfn1 KO cells were transfected with the Sec61β‐GFP plasmid and treated with 1 μM Tg for 24 h. Confocal microscopy images show ER vacuolization in Mfn2 KO cells treated with Tg. Scale bar: 10 μm. Insets show × 10 zoomed images. Scale bar: 5 μm.",
    "ncbi_link": "Mfn1: 67414
Mfn2: 170731
Sec61β: 66212"
  },
  {
    "caption": "(D) WT and Mfn2 KO cells were treated with Tg 1 μM for 3 h and then incubated with brefeldin A‐bodipy to stain ER and Golgi. Representative flow‐cytometry histograms (upper panel). Mean fluorescence intensity was used to quantify ER expansion (n=5) (lower panel). Data are mean±s.e.m. *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(A) WT and Mfn2 KO cells were treated with 1 μM Tg for 12 or 24 h. Total and cleaved caspase 3 levels were detected by western blot. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(B, C) WT and Mfn2 KO cells were treated with 0.5 μg/ml tunicamycin (Tm), 100 ng/ml brefeldin A (Bref), or 1 μM Tg for 24 h. Total and cleaved caspase 3 levels were detected by western blot (B) and caspase activity (C) by measurement of DEVD‐AFC substrate processing. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(D) Flow‐cytometry analysis of the Sub G1 DNA fragmentation in methanol‐fixed WT and Mfn2 KO cells after incubation with or without 1 μM Tg for 24 h. Data are given as mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(E) Scr (stably expressing scrambled shRNA) and Mfn2 knockdown (KD) (stably expressing shRNA directed against Mfn2) 3T3‐L1 fibroblasts were incubated in the presence or absence of 1 μM Tg for 24 h. Total and cleaved caspase 3 were detected by western blot. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(F) WT and Mfn2 KO cells were treated with 1 μM Tg for 24 h. Lactate dehydrogenase (LDH) release was analyzed by flow cytometry to assess necrotic cell death. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(G) WT and Mfn2 KO cells were incubated for 24 h with or without 1 μM Tg in the presence or absence of z‐VAD‐fmk and stained for annexin V/PI. Data are mean±s.e.m. (n=4). *P0.05 versus WT+Tg group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(H) Mfn2 KO cells transfected with the pEGFP plasmid were incubated with 1 μM Tg alone or in combination with 2 μM CHX for 24 h (3 h of pre‐incubation with CHX). Florescence microscopy images show that CHX prevents cytoplasmic vacuolization. Scale bar: 10 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(I) WT (black circles) and Mfn2 KO cells (white circles) were incubated with 1 μM Tg for varying times, and ALIX protein was detected by western blot. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(A, upper panel) WT (black circles) or Mfn2 KO cells (white circles) were treated with 1 μM Tg for a range of times. (A, lower) Densitometric quantification. Data are mean±s.e.m. (n=3). *P0.05 versus WT group; #P0.05 versus WT non‐Tg‐treated group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(B, upper panel) WT or Mfn2 KO cells were treated with Tg for 0, 6 or 12 h, in the presence or absence of Bafilomycin (Baf, 100 nM). LC3b‐I and LC3b‐II expression was measured by western blot. (B, lower panel) Densitometric quantification of LC3b‐II levels (relative to tubulin). Data are mean±s.e.m. (n=3). *P0.05 versus WT+Baf+Tg group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(C) WT or Mfn2 KO cells stably expressing mCherry‐GFP‐LC3b were treated with 1 μM Tg, 100 ng/ml Brefeldin (Bref), or 0.5 μg/ml tunicamycin (Tm) for 24 h and examined by confocal microscopy. Scale bar: 10 μm.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(E) Acidic compartments of WT or Mfn2 KO cells were stained with Lysotracker Green and analyzed by flow cytometry. Data are given as mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(F) LAMP1 expression was immunodetected in WT and Mfn2 KO cells in basal conditions.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(G) Expression of Beclin‐1 or LC3b transcripts in WT or Mfn2 KO cells treated with or without 1 μM Tg for 24 h. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Beclin‐1: 56208
LC3b: 67443
Mfn2: 170731"
  },
  {
    "caption": "(B) Immunodetection of p‐PERK,PERK, GADD34, p‐eIF2α, eIF2α, ATF4, CHOP, and XBP‐1s in WT and Mfn2 KO cells treated with 1 μM Tg for the times indicated.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(D) Immunodetection of p‐eIF2α, eIF2α, and ATF4 in WT and Mfn2 KO cells treated with 0.5 μg/ml Tunicamycin (Tm) for the times indicated.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(E) Transcriptional activity driven by ATF6. WT and Mfn2 KO cells were co‐transfected with the 5xATF6‐GL3 and TK‐Renilla plasmids and treated with 1 μM Tg for 24 h after transfection. Data are mean±s.e.m. (n=4). *P0.05 versus WT group.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "TK: 
ATF6: 226641
Mfn2: 170731"
  },
  {
    "caption": "(A) Immunodetection of PERK in WT and Mfn2 KO cells stably expressing a scrambled shRNA (Scr) or a shRNA directed against PERK (PERK KD).",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(B) Caspase activity was detected by measurement of DEVD-AFC substrate processing in WT or Mfn2 KO cells subjected to PERK silencing and treated with 1 μM Tg for 24 h. Data are mean±s.e.m. (n=3). *P0.05 versus WT; #P0.05 versus Scr group.",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(E, F) Immunodetection of LC3b‐I and ‐II in WT and Mfn2 KO cells subjected to PERK silencing and treated as indicated with Tg or Baf (1 μM Tg; 100 nM Baf) for 6 h. Densitometric quantification is shown in F. Data are mean±s.e.m. (n=3). *P0.05 versus WT; #P0.05 versus Scr group.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(A) Immunodetection of XBP‐1s in WT and Mfn2 KO cells stably expressing a scrambled shRNA (Scr) or a shRNA directed to XBP‐1 (XBP‐1 KD), and treated with Tg for 6 h.",
    "ncbi_link": "Mfn2: 170731
XBP‐1: 22433"
  },
  {
    "caption": "(C, D) Total and cleaved caspase 3 levels were detected by western blot. WT and Mfn2 KO cells subjected or not to XBP‐1 silencing (Scr, and KD) and treated with 1 μM Tg for 24 h. Data are mean±s.e.m. (n=3). *P0.05 versus WT group.",
    "ncbi_link": "Mfn2: 170731
XBP‐1: 22433"
  },
  {
    "caption": "(E, F) Immunodetection of LC3b‐I and ‐II in Scr and XBP‐1 KD WT or Mfn2 KO cells treated as indicated (1 μM Tg; 100 nM Baf) for 6 h. Densitometric quantification is shown in F. Data are mean±s.e.m. (n=3). #P0.05 versus Scr group.",
    "ncbi_link": "Mfn2: 170731
XBP‐1: 22433"
  },
  {
    "caption": "(G) Mfn2 KO cells stably expressing mCherry‐GFP‐LC3b and subjected or not to XBP‐1 silencing (Scr or KD) were treated with 1 μM Tg, 100 ng/ml Bref, or 0.5 μg/ml Tm for 24 h and examined by confocal microscopy. Scale bar: 10 μm.",
    "ncbi_link": "Mfn2: 170731
XBP‐1: 22433"
  },
  {
    "caption": "(A) Immunodetection of p‐PERK and p‐eIF2α in Mfn2 KO MEFs, Mfn2 knockdown 3T3‐L1 fibroblasts, and Mfn2 knockdown C2C12 myoblasts.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(C, D) Immunodetection of p‐eIF2α, eIF2α, CHOP, XBP‐1s, LC3b, and p62 in Mfn2‐deficient liver (C) or skeletal muscle (D) from tissue‐specific KO mice.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(E) Co‐immunoprecipitation of Mfn2 and PERK in WT or Mfn2 KO cells stably expressing PERK‐myc or an empty vector (pBABE‐myc; negative control).",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(A) Representative confocal images of mitochondrial morphology in scrambled (Scr) and PERK KD Mfn2 KO cells stained with MitoTracker Green.",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(C, D) Representative confocal images of mitochondrial morphology in scrambled (Scr) and PERK KD WT cells (C) or scrambled (Scr) and PERK KD Mfn1 KO cells (D) stained with MitoTracker Green.",
    "ncbi_link": "PERK: 13666
Mfn1: 67414"
  },
  {
    "caption": "(E) Representative confocal images of mitochondrial morphology in Mfn2 KO cells treated with 1 μM TUDCA or 10 mM 4‐phenyl butyric acid for 6 h and stained with MitoTracker Green.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(F) Flow‐cytometry quantification of ROS levels in Scr and PERK KD WT and Mfn2 KO cells",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(G) or Scr and PERK KD WT and Mfn1 cells using DHR1,2,3. Data are mean±s.e.m. (n=4). *P0.05 versus WT group, #P0.05 versus Scr group. Scale bars: 10 μm.",
    "ncbi_link": "PERK: 13666
Mfn1: 67414"
  },
  {
    "caption": "(A) Mitochondrial calcium overload in Scr and PERK KD Mfn2 KO cells. Cells were loaded with Rhod‐2 and then treated with 2.5 mM CaCl2 (left). Calcium uptake was monitored by confocal microscopy. Representative confocal images of mitochondrial morphology in WT and Mfn2 KO cells stained with Rhod‐2 and incubated with 2.5 mM CaCl2 for 5 min (right). Scale bars: 10 μm.",
    "ncbi_link": "PERK: 13666
Mfn2: 170731"
  },
  {
    "caption": "(B-E) Mitochondrial oxygen consumption (OCR) was measured in Scr and PERK KD Mfn2 KO cells (B), Scr and PERK KD WT cells (C), Scr and PERK KD Mfn1 KO cells (D), and WT cells stably expressing PERK‐myc (E). Data are mean of three independent experiments. The following parameters were measured: oxygen consumption under routine conditions (DMEM with 5.5 mM glucose), maximal respiratory capacity reached after uncoupling with FCCP, and respiratory leak, measured after inhibition of ATP synthase with oligomycin. Data are mean±s.e.m. *P0.05 versus Scr group or versus the empty plasmid group.",
    "ncbi_link": "PERK: 13666
Mfn1: 67414
Mfn2: 170731"
  },
  {
    "caption": "(F, G) Representative confocal images of mitochondrial morphology in WT cells stably expressing PERK‐myc stained with MitoTracker Green. Scale bars: 10 μm. Quantitative analysis of mitochondrial morphology is shown in G. Data are mean±s.e.m. (n=3). *P0.05 versus the empty plasmid group.",
    "ncbi_link": "PERK: 13666"
  },
  {
    "caption": "(a,b) Dynamics of HSFA2 and HSP101 transcript levels in control (NHS, NHS+187), 44°C heat-stressed non-colonized and SA187-colonized (HS, HS+187), thermoprimed (LAT) as well as thermoprimed and SA187-colonized plants (LAT+187) at 1 h, 24 h, 48 h, 72 h and 96 h of recovery at 22°C. SA187-colonized (HS+187) and thermoprimed (LAT) plants showed higher transcript levels in comparison to plants exposed at 44°C HS for 30 min (HS) after 1 h of recovery at 22°C. Data information: All plots represent the means of 3 biological replicates. Error bars represent SE. Asterisks indicate a statistical difference based on Student's t-test (*P ≤ 0.05",
    "ncbi_link": "HSFA2: 817155
HSP101: 843771"
  },
  {
    "caption": "(c,d). Transcript levels of heat stress memory genes HSP18.1 and APX2 in control plants (NHS, NHS+187), 44°C heat-stressed non-colonized and SA187-colonized (HS, HS+187), thermoprimed (LAT) as well as thermoprimed SA187-colonized plants (LAT+187) at 1 h, 24 h, 48 h, 72 h and 96 h of recovery at 22°C . Transcript levels were normalized to tubulin as reference gene and the respective 22°C NHS plants were harvested at the same time points. All treatments are compared with direct 44°C HS treatment for statistical significance. Data information: All plots represent the means of 3 biological replicates. Error bars represent SE. Asterisks indicate a statistical difference based on Student's t-test (*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001",
    "ncbi_link": "HSP18: 
tubulin: 
APX2: 820121"
  },
  {
    "caption": "(g) Relative enrichment of H3K4me3 at APX2 and HSP18.2 in control non-primed (NP), SA187-colonized non-primed plants (NP+187), 37°C-primed (P) and 37°C-primed SA187-colonized plants (P+187) at 24 and 72 h after priming as determined by chromatin immunoprecipitation-qPCR for the indicated regions of APX2 and HSP18.2. Amplification values were normalized to input and H3 and region 1 of non-primed (NP) plants. Data information: All plots represent the means of 3 biological replicates. Error bars represent SE. Asterisks indicate a statistical difference based on Student's t-test (*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001 for differences between NP in comparison to NP+187, P and P+187 treatments).",
    "ncbi_link": "APX2: 820121
HSP18.2: 836093"
  },
  {
    "caption": "(b,c) Fresh weight and percent survival of Col-0, hsfa2, hsfa1q and ein3-1 plants in HS, HS+187, LAT and LAT+187 treatments. Due to the dwarf size of hsfa1q mutants, LAT treatment was performed on d 18 and HS at d 20. All treatments are compared with plants upon 44°C HS. Data information: All plots represent the means of 3 biological replicates (n=36, 12 plants per biological repeat). Error bars represent SD of three biological repeats. Asterisks indicate a statistical difference based on the Student's t-test (* P≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001).",
    "ncbi_link": "hsfa1q: 
ein3: 821625
hsfa2: 817155"
  },
  {
    "caption": "(c) Relative enrichment of H3K4me3 at APX2 and HSP18.2 in control non-primed (NP), SA187-colonized non-primed plants (NP+187), 37°C-primed (P) and 37°C-primed SA187-colonized plants (P+187) at 24 and 72 h after priming as determined by chromatin immunoprecipitation-qPCR for the indicated regions of APX2 and HSP18.2 (Fig 3F). Data information: For H3K4me3 enrichment analysis, amplification values were normalized to input and H3 and region 1 of non-primed (NP) plants. All treatments are compared with direct 44°C HS treatment for statistical significance. All plots represent the means of 3 biological replicates. Error bars indicate SE. Asterisks indicate a statistical difference based on the Student's t-test *P ≤ 0.05; **P ≤ 0.01; **P ≤ 0.001 for differences between NP in comparison to NP+187, P and P+187 treatments.",
    "ncbi_link": "APX2: 820121
HSP18.2: 836093"
  },
  {
    "caption": "(f) Relative enrichment of H3K4me3 levels at APX2 and HSP18.2 memory genes in hsfa2 mutant. Data information: For H3K4me3 enrichment analysis, amplification values were normalized to input and H3 and region 1 of non-primed (NP) plants. All treatments are compared with direct 44°C HS treatment for statistical significance. All plots represent the means of 3 biological replicates. Error bars indicate SE. Asterisks indicate a statistical difference based on the Student's t-test *P ≤ 0.05; **P ≤ 0.01; **P ≤ 0.001 for differences between NP in comparison to NP+187, P and P+187 treatments.",
    "ncbi_link": "APX2: 820121
hsfa2: 817155
HSP18.2: 836093"
  },
  {
    "caption": "E. Ribosomal pull down shows lack of occupancy of ribosomes on veal2. fli1a and actb were used as positive controls.",
    "ncbi_link": "veal2: 
actb: 57934///57935
fli1a: 30619"
  },
  {
    "caption": "F-I. e-GFP fusion assay confirms lack of peptide formation from veal2 sequence. (F-G) mitfa-eGFP fused transcript. (H-I) veal2-eGFP fused transcript. Arrowheads indicating e-GFP expression in mitfa-eGFP injected embryos. Scale bar-100μm.",
    "ncbi_link": "eGFP: 
veal2: 
e-GFP: 
mitfa: 30080"
  },
  {
    "caption": "F-T. Representative images of 2 dpf zebrafish which displayed the rescue of the vascular integrity defects in the progeny of an outcross of veal2gib005Δ8/+ zebrafish upon complementing with the wild type (WT) veal2 RNA. (F-J) Control zebrafish embryos. (K-O) veal2gib005Δ8/+ embryos injected with vehicle control. (P-T) veal2gib005Δ8/+ embryos complemented with veal2 RNA. (F,K,P) bright field. (G,L,Q) mRFP. (H,M,R) Animals stained with O-dianisidine stain. (I,N,S) eGFP. (J,O,T) merged eGFP and mRFP filters. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. (F-H,K-M,P-R) magnification-5X, scale bar-100μm (I-J,N-O,S-T) magnification-20X, Scale bar-50μm.",
    "ncbi_link": "veal2: "
  },
  {
    "caption": "C. RNA immunoprecipitation of veal2 was performed by pull-down of Prkcbb and Epbhb3, followed by qRT-PCR. IgG pull-down was performed as control. Gel image shows the amplification of veal2 in different RNA immunoprecipitation samples, along with 10% input control, as marked by arrowheads.",
    "ncbi_link": "veal2: "
  },
  {
    "caption": "D. qRT-PCR based quantification of veal2 transcript across Prkcbb, Ephb3 and IgG immunoprecipitations. actb was used as normalization control. Data from three different biological replicates represented as mean fold change values ± standard deviation.",
    "ncbi_link": "veal2: 
actb: 57934///57935"
  },
  {
    "caption": "F-K. Enzastaurin treatment rescues hemorrhage phenotype in veal2gib005Δ8/+ zebrafish embryos indicated by rescue of the vascular integrity defects in veal2gib005Δ8/+. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. Experiment was repeated in biological replicates and total no of embryos scored are mentioned on figure. (F-I) Magnification-5X, Scale bar-100μm, (J-K) Magnification-20X, Scale bars-50μm.",
    "ncbi_link": "veal2: "
  },
  {
    "caption": "F. Abundance of Prkcbb protein in total cell (T), cytoplasmic (C) and membrane (M) fractions of cells from 2 dpf gib004Tg(fli1a:EGFP;gata1a:DsRed) and veal2gib005Δ8/+ zebrafish embryos. Arrowhead indicates Prkcbb enrichment in the membrane fraction of veal2gib005Δ8/+ zebrafish embryos.",
    "ncbi_link": "DsRed: 
EGFP: 
veal2: 
fli1a: 30619
gata1a: 30481"
  },
  {
    "caption": "E-H e-GFP fusion assay confirms lack of peptide formation from veal2 sequence. (E-F) mitfa-eGFP fused transcript. (G-H) VEAL2-eGFP fused transcript. Arrowheads indicating e-GFP expression in mitfa-eGFP injected embryos. Scale bar-100μ",
    "ncbi_link": "eGFP: 
veal2: 
VEAL2: 
e-GFP: 
mitfa: 30080"
  },
  {
    "caption": "I-N. Complementation of VEAL2 in veal2gib005Δ8/+ embryos significantly rescued hemorrhage phenotype. Arrowheads show the presence of hemorrhage due to the vascular integrity defects. (I-L) Magnification-5X, Scale bar-100μm (M-N) Magnification-20X, Scale bars-50μm.",
    "ncbi_link": "VEAL2: 
veal2: "
  },
  {
    "caption": "R-T. Co IF for PRKCB and smFISH of VEAL2 highlight their colocalization. (R) PRKCB in the GFP channel. (S) VEAL2 in CAL-fluor red (610nM). (T) Merged image for PRKCB and VEAL2. Magnification-100X, scale bar-20μm.",
    "ncbi_link": "VEAL2: "
  },
  {
    "caption": "K-AB. VEAL2 regulates junctional dynamics by interacting with PRKCB. Overexpression of VEAL2 retains PRKCB mostly in cytoplasm and keeps strong junctional assembly formation of CDH5 and CTNNB1 on the membrane. Knockdown of VEAL2 led to migration of PRKCB on membrane and henceforth degradation of junctional assembly of CDH5 and CTNNB1. (K-N,W-X) PRKCB. (O-R,Y-Z) CDH5. (S-V,AA-AB) CTNNB1. (K-V) Magnification-60X, Scale bar-15μm. Arrowheads indicate representation of signals of proteins in HUVECs. (W-AB) Dot plot representing quantification of protein signal localization in membrane/total fraction. The quantification was done using imageJ. Data from cells of different fields of 3 technical replicates of 1 biological replicate is presented as representation. Data is shown as individual values; the middle bar represents the mean and the error bar represents ± standard deviation.",
    "ncbi_link": "VEAL2: "
  },
  {
    "caption": "E-S. Modeling hyperglycemia in HUVEC resulted in dysregulation of junctional assembly of CDH5 and CTNNB1 proteins and increased membrane localization of PRKCB protein. Complementation of VEAL2 and veal2 in hyperglycemic conditions reverted junctional disassembly of CDH5 and CTNNB1 and also kept PRKCB in cytoplasm to mitigate pathological conditions associated with hyperglycemia. (E-H,Q) CDH5 protein, (I-L,R) CTNNB1 protein, (M-P,S) PRKCB protein. (E-P) Magnification-60X, Scale bar-15μm. Arrowheads indicate representation of signals of proteins in HUVECs. (Q-S) Data from cells of different fields of 3 technical replicates of 1 biological replicate is presented as representation. Data is shown as individual values; the middle bar represents the mean and the error bar represents ± standard deviation.",
    "ncbi_link": "VEAL2: 
veal2: "
  },
  {
    "caption": "B. Sagittal sections of C57BL/6J wild-type and KtyII-/- E7.5 embryos immunostained for Krt8 (n= 15 and n=5, respectively), F-actin (n=11 and 2), Vimentin (n=5 and 1), E-cadherin (n=1 and 1), T (n=4 and 3), Dsg2 (n=15 and 5) and Pecam-1 (n=4 and 3). Data information: White arrows point toward allantois and scale bars represent 25 µm.",
    "ncbi_link": "KtyII: 16679///16668///16678///110308///110310///223917///16691///406222///406219///100126226"
  },
  {
    "caption": "Quantification of embryo morphology at LB stage in C57BL/6J wild-type (white boxes/ black dots, n=22 including 16 in which allantois could be measured), and KtyII-/- embryos (grey boxes/ black triangles, n=9 including 8 in which allantois could be measured). (D) Embryonic region length. Ratios of whole embryo and ExE cavity lengths (E) , over embryonic region length.",
    "ncbi_link": "KtyII: 16668///16679///406219///406222///16691///223917///110310///110308///16678///100126226"
  },
  {
    "caption": "I-I''. SEM images of opened C57BL/6J wild-type (n=3) and KtyII-/- (n=2) LB stage embryos with zooms on the allantois region (I'-I''). Scale bars represent 200 (I), 20 (I') and 10 (I'') µm.",
    "ncbi_link": "KtyII: 100126226///406219///406222///16691///223917///110310///110308///16678///16668///16679"
  },
  {
    "caption": "J-K. Sections of C57BL/6J wild-type and KtyII-/- E7.5 embryos immunostained for Nrp1 (K) (n=8 and 2, respectively), and Lrp2 (L) (n=3 and 2).",
    "ncbi_link": "KtyII: 16678///16668///16679///100126226///406219///406222///16691///223917///110310///110308"
  },
  {
    "caption": "E. Immunostaining for Cdx2 (n=20). F. Immunostaining for DAPI (cyan, left), Sox2 (middle), and Gata2 (right). Sox2 is primarily expressed in Trophoblast Progenitors and Gata2 in Chorion Ectoderm. G. Immunostaining for Cebpb, detectable in most cells with variable intensity. H. Immunostaining for Fn1 (n=22), Dlk1 (n=8), and Acta2 (n=12), primarily expressed in Chorion Mesenchyme. I. Sections from C57BL/6J wild-type and KtyII-/- LB embryos immunostained for Dlk-1 (n=8 and 4, respectively) and Acta2 (n=6 and 3). Data",
    "ncbi_link": "KtyII: 16679///100126226///406219///406222///16691///223917///110310///110308///16678///16668"
  },
  {
    "caption": "K-L. Sections from C57BL/6J wild-type and KtyII-/- LB embryos immunostained for Cdh11 (Top) and Krt8 (Bottom) (K, n=8 and 4, respectively) and Ifitm3 (L, n=2 and 2). Data information: White arrows point toward signal in allantois. Sagittal sections with anterior to the left.",
    "ncbi_link": "KtyII: 406219///406222///16678///100126226///16668///16691///223917///16679///110310///110308"
  },
  {
    "caption": "(E) Intracellular cytokine staining assay of human TNF-α and IL-2 in sh-NC and sh-p38IP Jurkat E6.1 cells stimulated with 10 μg/ml anti-CD3 plus 2 μg/ml anti-CD28 for 6 hours (average frequency of positive staining YFP+ cells in sh-NC cells without stimulation = 1).",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(F) ELISA analysis of IL-2 and IL-6 production in the culture supernatants of human PBMCs transfected with si-NC or si-p38IP, and then stimulated with 10 μg/ml anti-CD3 plus 10 μg/ml anti-CD28 (αCD3/CD28) for 24 hours.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(G and H) Real-time PCR analysis of TNF-α, IL-6 and IL-1β (G) and of IFN-β, ISG54 and ISG56 (H) mRNA production in RAW264.7 cells transfected with si-NC and si-mp38IP-1 and then stimulated with 500 ng/ml LPS for the indicated times (average mRNA production in si-NC cells at 0 hour = 1).",
    "ncbi_link": "ISG56: 15957
ISG54: 15958
IFN-β: 15977
IL-1β: 16176
IL-6: 16193
p38IP: 55578
TNF-α: 21926"
  },
  {
    "caption": "(I) ELISA analysis of TNF-α, IL-6, IL-1β and IFN-β production in the culture supernatants of human PBMCs transfected with si-NC and si-p38IP and then stimulated with 1μg/mL LPS for 24 hours.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(A) Immunoblot analysis with the indicated antibodies of total cell lysates of sh-NC and sh-p38IP Jurkat E6.1 cells stimulated with 10 μg/ml anti-CD3 plus 2 μg/ml anti-CD28 for the indicated times. Actin served as a loading control (throughout).",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(B) Statistical analysis of p65 nuclear translocation of sh-NC and sh-p38IP Jurkat E6.1 T cells stimulated with 50 ng/ml PMA plus 1µM ionomycin for the indicated times. p65 nuclear translocation was indicated by the fluorescence intensities ratio between the nuclear p65 and the whole cell p65 from each cell. ***P < 0.001 (two-tailed unpaired t-test, mean and s.e.m.).",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(C) Luciferase reporter assay of sh-NC and sh-p38IP Jurkat E6.1 cells transfected with NF-κB luc plus an internal control Renilla luciferase reporter for 36 hours, followed by stimulation with ( + ) or without ( - ) 50ng/ml PMA plus 1 µM ionomycin for 8 hours. ***P < 0.001; n.s., not significant (two-tailed unpaired t-test, mean and s.e.m.).",
    "ncbi_link": "luc: 
luciferase: 
p38IP: 55578"
  },
  {
    "caption": "(D,E) Immunoblot analysis with the indicated antibodies of total cell lysates of RAW264.7 cells transfected with si-NC and si-mp38IP-1 and then stimulated with 500 ng/ml LPS for the indicated times.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(B) HEK293T cells were transfected with YFP-p38IP, and the cell lysates aliquots were immunoprecipitated with IgG, anti-TAB1, anti-TAB2 and anti-TAK1 respectively, and then immunoblotted with the indicated antibodies.",
    "ncbi_link": "YFP: 
p38IP: 55578"
  },
  {
    "caption": "(C) sh-NC or sh-p38IP Jurkat E6.1 T cells were stimulated with 10 μg/ml anti-CD3 plus 2 μg/ml anti-CD28 for the indicated times and lysed, followed byTAK1 immunoprecipitation. TAK1 beads were washed three times with lysis buffer and two times with kinase buffer, then resuspended in kinase buffer containing 100 μM ATP and 1μg recombinant GST-IKKβ(111-250aa) protein as substrate to perform in vitro kinase assay, and then immunoblot analysis with p-IKKβ antibody.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(D) HEK293T cells were transfected with cMyc vector ( - ) or increasing amounts of cMyc-p38IP (wedge), and 24 hours post transfection, the cell lysates were immunoprecipitated with IgG or anti-TAB2 and then immunoblotted with anti-TAK1 and anti-TAB2. Expression of cMyc-p38IP was determined in the immunoblotted lysates with anti-cMyc.",
    "ncbi_link": "cMyc: 
p38IP: 55578"
  },
  {
    "caption": "(E) HEK293T cells were transfected with HA vector ( - ) or increasing amount of HA-p38IP (wedge), and 24 hours post transfection, the cell lysates were immunoprecipitated with IgG or anti-TAK1 and then immunoblotted with anti-TAB2, anti-TAB1, anti-HA and anti-TAK1. Expression of HA-p38IP was determined in the immunoblotted lysates with anti-HA.",
    "ncbi_link": "HA: 
p38IP: 55578"
  },
  {
    "caption": "(F) sh-NC and sh-p38IP Jurkat E6.1 T cells were stimulated with 10 μg/ml anti-CD3 plus 2 μg/ml anti-CD28 for the indicated times, and the cell lysates were immunoprecipitated with anti-TAB2 and immunoblotted with anti-TAK1 and anti-TAB2.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(H) Jurkat TAg T cells transfected with cMyc vector or cMyc-p38IP were stimulated with 10μg/ml anti-CD3 for the indicated times, and then were lysed and immunoprecipitated with anti-TAK1 antibody and immunoblotted with anti-K63Ub, anti-cMyc and anti-TAK1 antibodies. Lysates were blotted with the indicated antibodies, and actin served as the loading control.",
    "ncbi_link": "cMyc: 
p38IP: 55578"
  },
  {
    "caption": "(I) sh-NC and sh-p38IP Jurkat E6.1 T cells stimulated as in (F) were lysed and immunoprecipitated with anti-TAK1 and immunoblotted with anti-K63Ub and anti-TAK1. Lysates were immunoblotted with the indicated antibodies.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(K) sh-NC and sh-p38IP Jurkat E6.1 cells stimulated as in (F) were lysed and immunoprecipitated with anti-TAB2 and immunoblotted with anti-K63Ub and anti-TAB2. Data (B-F, H-K) are representatives of at least three independent experiments.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(B) HEK293T cells transfected with Flag-tagged TAB2 (open arrow) or TAB2-ub (solid arrow) were lysed and immunoprecipitated with anti-Flag, and then immunoblotted with the indicated antibodies. The asterisk indicates a non-specific band. The relative intensity of the IP bands was quantified by densitometry and is presented in the right.",
    "ncbi_link": "Flag: 
TAB2: 23118"
  },
  {
    "caption": "(C) HEK293T cells co-transfected with HA-tagged p38IP together with cMyc-tagged TAK1 (open arrow) or ub-TAK1 (solid arrow) were lysed and immunoprecipitated with anti-cMyc, and then immunoblotted with the indicated antibodies. Asterisk indicates non-specific bands. The relative intensity of the IP bands was quantified by densitometry and is presented in the right.",
    "ncbi_link": "cMyc: 
HA: 
p38IP: 55578
TAK1: 23118"
  },
  {
    "caption": "(D) HEK293T cells co-transfected with HA-tagged p38IP, Flag-tagged TAB2-ub, together with cMyc-tagged TAK1 (open arrow) or ub-TAK1 (solid arrow), were lysed and immunoprecipitated with anti-cMyc, and then immunoblotted with the indicated antibodies. The relative intensity of the IP bands was quantified by densitometry and is presented in the right.",
    "ncbi_link": "cMyc: 
Flag: 
HA: 
p38IP: 55578
TAB2: 23118
TAK1: 23118"
  },
  {
    "caption": "(B) HEK293T cells transfected with N-terminal (left panels) or C-terminal (right panels) deletion mutants of p38IP as indicated in (A) were lysed after 24 hours transfection and immunoprecipitated with IgG or anti-TAK1, followed by incubation with protein G beads, and then immunoblotted with anti-YFP and anti-TAK1.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(E) HEK293T cells transfected with YFP-p38IP T1B were lysed after 24 hours transfection and immunoprecipitated with IgG or anti-TAK1, followed by incubation with protein G beads, and then immunoblotted with anti-YFP and anti-TAK1.",
    "ncbi_link": "YFP: 
p38IP: 55578"
  },
  {
    "caption": "(F) Jurkat TAg cells transfected with YFP vector or YFP-T1B were stimulated with 10μg/ml anti-CD3 for indicated times, then lysed and immunoprecipitated with anti-TAK1, followed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "YFP: "
  },
  {
    "caption": "(G) Primary human PBMCs transfected with YFP vector or YFP-T1Bwere stimulated with 10 μg/ml anti-CD3 plus 10 μg/ml anti-CD28 for the indicated times, then lysed and analyzed by immunoblotting.",
    "ncbi_link": "YFP: "
  },
  {
    "caption": "(A) HEK293T cells co-transfected with YFP-p38IP and Flag-vector, Flag-USP3 or Flag-USP4 as indicated were lysed and immunoprecipitated with anti-Flag antibody and immunoblotted with indicated antibodies.",
    "ncbi_link": "Flag: 
YFP: 
p38IP: 55578
USP3: 9960
USP4: 7375"
  },
  {
    "caption": "(B) HEK293T cells transfected with Flag-USP4 and YFP-vector or YFP-p38IP as indicated were lysed and immunoprecipitated with anti-IgG or anti-TAK1 and then immunoblotted with anti-Flag and anti-TAK1.",
    "ncbi_link": "Flag: 
YFP: 
p38IP: 55578
USP4: 7375"
  },
  {
    "caption": "(E) sh-NC and sh-p38IP Jurkat E6.1 cells transfected with si-NC, si-p38IP, Flag or Flag-USP4 as indicated were stimulated with anti-CD3/CD28 for 0 and 15 min at 48 hours post transfection, and then lysed and immunoprecipitated with anti-TAK1 under stringent conditions and immunoblotted with anti-ub. Statistical analysis of p-p38 levels was shown below the blot. **P < 0.01; n.s., not significant (two-tailed unpaired t-test, mean and s.e.m.).",
    "ncbi_link": "Flag: 
p38IP: 55578
USP4: 7375"
  },
  {
    "caption": "(G) sh-NC and sh-p38IP Jurkat E6.1 cells were stimulated with 10 μg/ml anti-CD3 plus 2 μg/ml anti-CD28 for the indicated times, and then lysed and immunoprecipitated with anti-TAK1 and immunoblotted with anti-USP4 and anti-TAK1.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(H) Mapping the USP4 binding domain of p38IP.",
    "ncbi_link": "USP4: 7375"
  },
  {
    "caption": "c, Transmission electron microscopy (TEM) of crypts. Note autophagic vacuoles in various stages of evolution in Xbp1 Dgr;IEC hypomorphic Paneth cells.",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "b, Representative haematoxylin and eosin stainings. Note transmural inflammation extending through muscularis propria (white arrow) into serosa (black arrow) in Atg7/Xbp1Dgr;IEC and Atg16l1/Xbp1Dgr;IEC mice scored in c and e. Scale bars, 50 µm, except for lower two panels (10 µm). c, Enteritis histology score (n = 26/12/18/27; 10-18 weeks; median shown; Kruskal-Wallis with post-hoc Holm's-corrected Mann-Whitney U-test).e, Enteritis histology score (n = 11; 18 weeks; median shown; Kruskal-Wallis with post-hoc Holm's-corrected Mann-Whitney U-test). NS, not significant.",
    "ncbi_link": "Atg16l1: 77040
Atg7: 74244
Xbp1: 22433"
  },
  {
    "caption": "f, Xbp1 mRNA splicing (Xbp1u, unspliced; Xbp1s, spliced) of crypts; densitometry in g (n = 7; unpaired Student's t-test; mean ± s.e.m.).",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "a, shCtrl or shXbp1 MODE-K cells were co-silenced for Atg16l1 (siAtg16l1) or with scrambled siRNA (siCtrl), and analysed by flow cytometry for annexin V and propidium iodide (PI; n = 3; one-way ANOVA with post-hoc Bonferroni; mean ± s.e.m.).",
    "ncbi_link": "Atg16l1: 77040
Xbp1: 22433"
  },
  {
    "caption": "c, Immunoblot of cytoplasmic extracts from shCtrl or shXbp1 MODE-K cells after TNF stimulation.",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "c, Representative images of EYFP-Rosa26/D6-cre+/- reporter mice and EYFP-Rosa26 (controls). Co-localization of Defa6 Cre-driven EYFP expression (yellow) with lysozyme-expressing Paneth cells (red; n = 3). DAPI, blue; scale bars, 50 µm.",
    "ncbi_link": "cre: 
Cre: 
Defa6: 13240
Rosa26: 14910"
  },
  {
    "caption": "d, Immunoblots of crypt intestinal epithelial cells from Xbp1Dgr;PC and wild-type controls (n = 2).",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "h, Representative haematoxylin and eosin images of Xbp1Dgr;PC and wild-type mice scored in i. Scale bars, 50 µm. i, Enteritis scoring in Xbp1fl/fl (WTfl), Defa6-cre+ (WTcre) and Defa6-cre+;Xbp1fl/fl (Xbp1Dgr;PC) mice (n = 21/26/29; median shown; Kruskal-Wallis with post-hoc Holm's-corrected Mann-Whitney U-test). Results represent two (b, d) independent experiments. *P 0.05, **P 0.01, ***P 0.001.",
    "ncbi_link": "cre: 
Defa6: 13240
Xbp1: 22433"
  },
  {
    "caption": "Heat map summarizing detection of EGFR and PTEN alterations in tumor tissue and in CSF samples. Shared detection in tissue and CSF is indicated in green, detection of the alteration only in tissue in orange, and non-detection in blue. The top bars indicate the cfDNA concentration (copies/mL; in a range of purples), the size of the tumors (in a range of browns), the type of glioma (in a range of blues), and whether the tumor was in direct contact with the CSF or not (based on MRI, green or red, respectively). Samples are ranked from the left to right by decreasing concentration of cfDNA (copies/mL)",
    "ncbi_link": "EGFR: 1956
PTEN: 5728"
  },
  {
    "caption": "E. Substrate-binding pocket mutations Y90A and Y74A/Y90A/T105A/S107K affect the ability of ectopically expressed spMis18fl to rescue the temperature sensitivity of mis18-262 cells to varying degrees. Five-fold serial dilutions of mis18-262 cells transformed with plasmids harbouring the indicated spMis18fl constructs, spotted on PMG - uracil + Phloxine B media supplemented with (repressed) or without (expressed) thiamine, and incubated at the indicated temperatures; dead cells stain dark pink.",
    "ncbi_link": "mis18: 2538763
Mis18: 2538763"
  },
  {
    "caption": "B. Size Exclusion Chromatography (SEC) and SEC-MALS (SEC combined with Multi Angle Light scattering) analyses of the recombinant wild-type (wt) and dimer disrupting mutant (I31A) of spMis181-120. Measured molecular weights from SEC-MALS confirm that spMis181-120 wt is a dimer in solution and spMis181-120 I31A is a monomer.",
    "ncbi_link": "Mis18: 2538763"
  },
  {
    "caption": "E. SDS-PAGE analysis of the GST-pull down assay where wt and dimer disrupting mutants of hsMis18α77-187 and hsMis18β56-183 were co-expressed as His- and GST-tagged proteins, respectively in E. coli. While wt GST-hsMis18β56-183 showed interaction with wt His-hsMis18α77-187, hsMis18 proteins harbouring dimer-disrupting mutations, GST-hsMis18β56-183 V77E/Y172D and His-hsMis18α77-187 V82E/Y176D did not show noticeable interaction. The corresponding Ni-NTA pull downs showing the expression of His-tagged proteins are shown in Fig EV2D.",
    "ncbi_link": "Mis18: 54069///11339"
  },
  {
    "caption": "A & B. SEC-MALS analysis of His-GFP-spMis18fl and His-spMis18ΔC, respectively. Refractive index (RI, left Y-axis) and molecular mass (kDa, right Y-axis) profiles show that both His-GFP-spMis18fl (predicted MW of a monomer is 51.97 kDa) and His-spMis18ΔC (Predicted MW of a monomer 21.8 kDa) predominantly exist as tetramers (187.6 kDa and 78.6 kDa, respectively) with a small population of dimer (128.5 kDa and 45.8 kDa, respectively).",
    "ncbi_link": "Mis18: 2538763"
  },
  {
    "caption": "C. SEC profile of a sample containing an equimolar mixture of purified His-GFP-spMis18C-term-α and His-spMis18MeDiY (upper panel) and SDS-PAGE analysis of SEC-fractions (bottom panel). His-GFP-spMis18C-term-α and His-spMis18MeDiY eluted separately at 12.3 and 15.3 ml, respectively, demonstrating the inability of these domains to interact with each other.",
    "ncbi_link": "Mis18: 2538763"
  },
  {
    "caption": "A. spMis18fl-Myc co-immunoprecipitates with both GFP-tagged spMis18fl and spMis18MeDiY, but shows reduced association when MeDiY-mediated dimerization is disrupted in spMis18flI31A. The asterisk (*) in the top panel denotes the IgG heavy chain.",
    "ncbi_link": "Mis18: 2538763"
  },
  {
    "caption": "B & C. Dimer-II interface mutations I31A and Y114A affect the ability of ectopically expressed spMis18fl to rescue the temperature sensitivity of mis18-818 and mis18-262 cells, while expression of spMis18MeDiY alone confers a dominant negative effect on growth in a MeDiY dimerization-dependent manner. Five-fold serial dilutions of cells expressing the indicated spMis18 constructs integrated at the leu1 locus in the genome, spotted on complete PMG + Phloxine B media supplemented with (repressed) or without (expressed) thiamine, and incubated at the indicated temperatures; dead cells stain dark pink.",
    "ncbi_link": "Mis18: 2538763
mis18: 2538763"
  },
  {
    "caption": "D. Mutations that disrupt MeDiY dimerization lead to reduced levels of spMis18fl association with centromeres. qChIP analyses of spMis18fl-GFP association with centromere 2 (cc2) in the indicated strains when grown in complete PMG media supplemented with (repressed) or without (expressed) thiamine. Error bars represent standard deviation between at least three biological replicates.",
    "ncbi_link": "Mis18: 2538763"
  },
  {
    "caption": "C DNA breaks were measured using alkaline comet assay in BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) human DLD1 cells treated with 2 µM pyridostatin (PDS) for 16 hours and released into fresh medium without pyridostatin. Representative images are shown. Scale bar represents 100 µm. D Quantification of DNA breaks shown in (C). Graph and error bars represent the mean and SEM of n = 3 independent experiments. A minimum of 50 cells were analysed per condition per experiment. P values were calculated using an unpaired two-tailed t-test. *, P ≤ 0.05; NS, P > 0.5. E Quantification of γH2AX foci visualised using immunofluorescence staining in cells treated as in (C). A minimum of 200 cells were analysed per condition per experiment. Graph and error bars represent the mean and SEM of n = 3 independent experiments. P values were calculated using an unpaired two-tailed t-test. ***, P ≤ 0.001; NS, P > 0.5.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "F BRCA2-deficient (-BRCA2) human DLD1 cells were treated with 2 µM pyridostatin (PDS) for 24 hours. Next, pyridostatin was removed and cells were released in a medium containing 250 nM NU-7441 (NU). Whole-cell extracts were prepared at the indicated timepoints after release and immunoblotted as shown. SMC1 was used as a loading control. KAP1 phosphorylation site is indicated in red.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "G Dose-dependent viability assays of BRCA2-proficient (+BRCA2) or -deficient (-BRCA2) human DLD1 cells treated with pyridostatin (PDS) and NU-7441 at the indicated concentrations for six days. Graphs represent average values obtained from of n = 3 independent experiments, each performed in technical triplicates.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Quantitative RT-PCR of cells grown as in (A) and treated with 10 µM pyridostatin (PDS) for 3 days was performed using primers specific for the indicated genes. mRNA levels are expressed relative to GAPDH and to -DOX (+BRCA2) cells. Error bars represent the SEM of n = 3 independent experiments, each performed in technical triplicate. P values were calculated using an unpaired two-tailed t-test. *, P ≤ 0.05; ***, P ≤ 0.001.",
    "ncbi_link": "BRCA2: 675
GAPDH: 2597"
  },
  {
    "caption": "BRCA2+/+ and BRCA2-/- RPE-1 cells were treated with 10 μM pyridostatin (PDS) for 2 days. Whole-cell extracts were immunoblotted as indicated. KAP1, IRF3 and STAT1 phosphorylation sites are shown in red. Tubulin and GAPDH were used as loading controls.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "H1299+shBRCA2DOX cells treated as in (B) were fixed and prepared for immunofluorescence with antibody against cGAS. DNA was counterstained with DAPI. Scale bar represents 20 µm. Quantification of cGAS-positive micronuclei per cells shown in (E). Graph and error bars represent the mean and SEM of of n = 3 independent experiments. A minimum of 250 cells were analysed per condition per experiment. P values were calculated using an unpaired two-tailed t-test. *, P ≤ 0.05; **, P ≤ 0.01; NS, P > 0.5.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "FVB female mice were injected intramuscularly with (A) BRCA1-proficient KP3.33 (Brca1+/+) or (B) BRCA1/53BP1-deficient KB1PM5 (Brca1-/-, Tp53bp1-/-) mouse mammary tumour cells. Pyridostatin (PDS) was administered intravenously (i.v.; 7.5 mg/kg/day) and talazoparib was administered orally (p.o.; 0.33 mg/kg/day), over the indicated periods of time. Vertical dotted line indicates end of treatment. Tumour volume was measured at the timepoints shown on the graph and expressed relative to tumour volume at the beginning of treatment. Each experimental group included n = 5 mice. Error bars represent SEM. P values were calculated between treated and untreated tumours at day 16, using an unpaired two-tailed t-test. ****, P ≤ 0.0001; NS, P > 0.5.",
    "ncbi_link": "Brca1: 12189
BRCA1: 12189
53BP1: 27223
Tp53bp1: 27223"
  },
  {
    "caption": "BRCA1+/+, BRCA1-/- and BRCA1-/-/TP53BP1-/- RPE-1 cells were treated with 10 μM pyridostatin (PDS) or 2 μM olaparib for 2 days. Whole-cell extracts were immunoblotted as indicated. KAP1, IRF3 and STAT1 phosphorylation sites are shown in red. SMC1 and GAPDH were used as loading controls.",
    "ncbi_link": "BRCA1: 672
TP53BP1: 7158"
  },
  {
    "caption": "(B) Direct sequencing of PARN in a control, P1 and her parents.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(D) Direct sequencing of PARN in a control, P2 and her parents.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(E) Aberrant splicing products detected in P2 and her mother but not in P2's father nor in a healthy control. GAPDH RT-PCR was performed as control.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "(A) Validation of PARN KO in HT1080 cells by Western blot. GAPDH is used as loading control.",
    "ncbi_link": "GAPDH: 
PARN: 5073"
  },
  {
    "caption": "(B) In vitro deadenylation activity assay using protein extracts from HT1080 (WT) and HT1080PARN KO (PARN KO) cells.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(C) TRAP assay using successive dilutions (500 ng, 250 ng, 125 ng and 62.5 ng) of cell extracts from WT or PARN KO cells. An internal control (IC) for PCR was used.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(D) qRT-PCR analysis of hTR expression in WT and PARN KO cells. Expression levels were normalized first to ACTB and then to WT. Three independent RNA extractions were performed for each cell line. Error bars indicate s.e.m..",
    "ncbi_link": "PARN: 5073
hTR: 7012"
  },
  {
    "caption": "(E) Representative pictures of FISH against hTR in WT and PARN KO cells. Arrows indicate hTR foci. Scale bar 5 μm.",
    "ncbi_link": "hTR: 
PARN: 5073"
  },
  {
    "caption": "(F) PARN detection by Western blot in the indicated conditions. Expression was induced by incubating cells with 10 ng/ml doxycycline for 72 h. Actin is used as loading control. PARN/actin ratios, normalized to doxycycline-treated WT/PARN cells, are shown below.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(G) In vitro deadenylation activity assay using protein extracts from doxycycline-treated WT/empty, WT/PARN, KO/empty and KO/PARN cells.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(H) qRT-PCR analysis of the indicated gene transcripts in doxycycline-treated WT/empty, WT/PARN, KO/empty and KO/PARN cells. Expression levels were normalized first to ACTB and then to WT/empty. Three independent doxycycline inductions were performed for each cell line. Averages are shown and error bars indicate s.e.m.. Unpaired Student's t tests were applied.",
    "ncbi_link": "ACTB: 
PARN: 5073"
  },
  {
    "caption": "(J) Same as (H) for p53 and p21 transcripts. Averages are shown and error bars indicate s.e.m.. Unpaired Student's t tests were applied.",
    "ncbi_link": "p21: 1026
p53: 7157"
  },
  {
    "caption": "(K) qRT-PCR analysis of TERRA from the indicated chromosome ends in doxycycline-treated KO/empty and KO/PARN cells. Expression levels were normalized first to ACTB and then to KO/empty. Three independent doxycycline inductions were performed for each cell line. Error bars indicate s.e.m..",
    "ncbi_link": "ACTB: 
PARN: 5073"
  },
  {
    "caption": "(A) Analysis of telomeric aberrations by Telo-FISH in doxycycline-treated WT/empty, WT/PARN, KO/empty and KO/PARN cells. Two independent experiments were performed. Counted chromatids: WT/empty: n=1824; WT/PARN: n= 1744; KO/empty: n=1452; KO/PARN: n=1920. Averages are shown and χ2-tests were applied to compare KO/empty with either WT/empty or KO/PARN.",
    "ncbi_link": "PARN: 5073"
  },
  {
    "caption": "(B) TRF analysis of telomere length (kb) in KO/empty and KO/PARN cells treated with 10 ng/ml Dox for 72h. A control Western blot with PARN and Actin is shown below for the corresponding samples.",
    "ncbi_link": "Actin: 
PARN: 5073"
  },
  {
    "caption": "(A) HT1080 (WT) and HT1080PARN KO (KO) cells stably transfected with GFP plasmid (empty) were transfected with siRNAs against p53 for 72h before RNA extraction and qRT-PCR. siRNAs against luciferase (siLuci) were used as control. p53 expression levels were normalized first to ACTB and then to WT/empty/siLuci cells. Experiment was performed in triplicate. Error bars indicate s.e.m.",
    "ncbi_link": "ACTB: 
GFP: 
luciferase: 
PARN: 5073
p53: 7157"
  },
  {
    "caption": "(B) Cells were treated as in (A) and transcript levels of the indicated genes were measured by qRT-PCR. cDNA expression levels were normalized first to ACTB and then to WT/empty/siLuci cells. Experiment was performed in triplicate. Error bars indicate s.e.m.",
    "ncbi_link": "ACTB: "
  },
  {
    "caption": "(C) Northern blot analysis of pre-rRNAs from control and patient B-LCLs. (D) Log2 values of 18S-E/21S and 18S-EFL/21S for P1 and P2 were normalized to the values of the control and presented in a graphical format, as Log averages + standard deviation for two independent experiments.",
    "ncbi_link": "21S: 
18S-E: 106632259///106632258///106631781///109864280///110255165///109910380///109864273///110255169"
  },
  {
    "caption": "(E) Northern blot analysis of pre-rRNAs from HT1080PARN WT and HT1080PARN KO cells, transduced with an empty vector. (F) Ectopic expression of PARN was induced in HT1080PARN KO cells and compared to cells transduced with an empty vector. Western blot relative to actin assessed PARN levels. (G) Quantitative analyses of 18S-E/21S and 18S-E FL/21S ratios were as described in (D) for HT1080PARN KO cells relative to HT1080PARN WT (left panel; see (E)), and for HT1080PARN KO cells rescued by ectopic expression of PARN relative to HT1080PARN KO cells transduced with an empty expression vector (right panel; see (F)), with Log averages + standard deviation for four independent experiments.",
    "ncbi_link": "21S: 
PARN: 5073
18S-E: 106632259///106632258///106631781///109864280///110255165///109910380///109864273///110255169"
  },
  {
    "caption": "(A) Western blot analysis of Parn expression in control and Parn+/- MEFs.",
    "ncbi_link": "Parn: 74108"
  },
  {
    "caption": "(B) Northern blot analysis of total RNAs from WT and Parn+/- MEFs.",
    "ncbi_link": "Parn: 74108"
  },
  {
    "caption": "(D) Frequencies of expected and observed newborns of the indicated genotype obtained from Parn+/- intercrosses. n indicates the number of animal analyzed. Statistical significance (P = 1.5417E-08) of the differences between the observed and expected genotype distributions was assessed by χ2-test. (E) Frequencies of expected and observed E11.5 embryos of the indicated genotype obtained from Parn+/- intercrosses. n indicates the number of animal analysed. Statistical significance (P = 0.02535) of the differences between the observed and expected genotype distributions was assessed by χ2-test.",
    "ncbi_link": "Parn: 74108"
  },
  {
    "caption": "(F), (G) p53 knock-out does not rescue Parn-/-. No Parn-/- p53-/- mouse was born from various combinations of Parn+/- and either p53+/- or p53-/- crosses (49 and 56 pups, respectively). Statistical significance (P = 0.000886) of the differences between the observed and expected genotype distributions was assessed by χ2-test.",
    "ncbi_link": "Parn: 74108
p53: 22059"
  },
  {
    "caption": "qRT-PCR with primers specific to both wild-type and mutant RNAPII (left panel) or to the mutant form of RNAPII (right panel), confirming that only the slow version of RNAPII is expressed in homozygous slow/slow ESCs. The sequences of the respective forward primers are shown. The "WT/slow allele" primer is complementary to the sequence in exon 14 upstream of the mutation. The "slow allele only" primer has its 3' end matching the mutated codon 749 and does not anneal to the WT DNA sequence. The mean ± SEM is plotted, n=2.",
    "ncbi_link": "RNAPII: 20020"
  },
  {
    "caption": "E. GSK3 wild-type (WT) and knockout (KO) cells were treated with CHX (100 µg/ml) for indicated times, and FoxM1 and GSK3α/β expression levels were determined by Western blotting.",
    "ncbi_link": "GSK3: 606496///56637"
  },
  {
    "caption": "F. Flag-FoxM1 and GSK3βKA or GSK3βKD plasmids were co-transfected into 293T cells for 48 hr. The cells were then treated with CHX (100 µg/ml) for indicated times. Exogenous Flag-FoxM1 expression level was determined by Western blotting.",
    "ncbi_link": "GSK3β: 2932"
  },
  {
    "caption": "D. HA-ubiquitin and Flag-tagged FoxM1 (WT) or mutants FoxM1S228A, FoxM1T309A, or Flag-FoxM1S474A plasmid were co-transfected into 293T cells. After 36 hr, cells were treated with 25 nM MG132 for 6 hr. Cell lysates were subjected to IP with Flag antibody, followed by IB with Flag and HA antibody.",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "E. HA-ubiquitin was co-transfected into 293T cells. After 36 hr, cells were treated with 25 nM MG132 for 6 hr. Cell lysates were subjected to IP with IgG or FoxM1 phospho-S474 antibody, followed by IB with FoxM1 and HA antibody.",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "F. HA-tagged K48-only ubiquitin or K63-only ubiquitin construct was transfected into 293T cells. After 36 hr, cells were treated with 25 nM MG132 for 6 hr. Cell lysates were subjected to IP with IgG or FoxM1 antibody, followed by IB with FoxM1 and HA antibody.",
    "ncbi_link": "ubiquitin: 7311///6233///7316///7314"
  },
  {
    "caption": "G. GSK3βCA or vector and Flag-tagged FoxM1 (WT), mutants S474A or S478A were co-transfected into 293T cells. Lysates of the cells were subjected to IP with Flag antibody and followed by IB with FoxM1 phospho-S474 antibody.",
    "ncbi_link": "FoxM1: 2305
GSK3β: 2932"
  },
  {
    "caption": "B. Axin siRNA or control siRNA were transfected into LN229 cells, after 36 hours, lysate of the cells was performed with co-IP using FoxM1 antibody followed by IB with indicated antibodies.",
    "ncbi_link": "Axin: 8313///8312"
  },
  {
    "caption": "C. Axin siRNA or control siRNA were transfected into LN229 cells for 36 hours. Lysates of the cells were subjected to IB with FoxM1 phospho-S474 antibody.",
    "ncbi_link": "Axin: 8313///8312"
  },
  {
    "caption": "G. HA-Ubiquitin and/or FBXW7, GSK3β CA, Flag-FoxM1 were co-transfected into 293T cells, after 36 hours, cells were treated with MG132 for six hours. Then lysate of the cells was performed with IP using Flag antibody followed by IB with indicated antibodies.",
    "ncbi_link": "FBXW7: 55294
FoxM1: 2305
GSK3β: 2932"
  },
  {
    "caption": "H. FBXW7 siRNA or control siRNA and HA-Ubiquitin were transfected into 293T cells, after 36 hours, cells were treated with MG132 with or without Wnt-3a (50 ng/ml) for six hours. Then lysate of the cells was performed with IP using FoxM1 antibody followed by IB with indicated antibodies.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "C. GSK3-β CA, USP5, or control plasmid was co-transfected with Flag-FoxM1 into 293T cells. After 36 hr of transfection, cells were treated with 50 ng/ml Wnt-3a or control PBS for 4 hr. Cell lysates were subjected to IP with USP5 antibody and followed by IB with Flag or USP5 antibody.",
    "ncbi_link": "GSK3-β: 2932
USP5: 8078"
  },
  {
    "caption": "D. GSK3βCA, USP5, or control plasmid was co-transfected with Flag-FoxM1 into 293T cells. After 36 hr of transfection, cells were treated with 50 ng/ml Wnt-3a or control PBS for 6 hr. Cell lysates were subjected to USP5 with Flag antibody and followed by USP5 with Flag or USP5 antibody.",
    "ncbi_link": "GSK3β: 2932
USP5: 8078"
  },
  {
    "caption": "E. USP5 and Flag-FoxM1 (WT) or mutants Flag-FoxM1S474A or Flag-FoxM1S474E plasmids were co-transfected into 293T cells for 36 hr. Cell lysates were subjected to IP with Flag antibody and followed by IB with Flag or USP5 antibody.",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "F. GSK3β CA, USP5, or control plasmid was co-transfected with Flag-FoxM1 (WT) or mutants Flag-FoxM1S474A into 293T cells for 36 hr. Cell lysates were subjected to IP with Flag antibody and followed by IB with Flag or USP5 antibody.",
    "ncbi_link": "FoxM1: 2305
GSK3β: 2932"
  },
  {
    "caption": "G. HA-ubiquitin and Flag-FoxM1 were co-transfected with or without GSK3β CA into 293T cells. After 36 hr, cells were treated with 25 nM MG132 for 6 hr. Cell lysates were subjected to IP with Flag followed by IB with HA or FoxM1 antibody.",
    "ncbi_link": "FoxM1: 2305
GSK3β: 2932"
  },
  {
    "caption": "H. HA-ubiquitin and Flag-FoxM1 were co-transfected with or without siUSP5 into U87 cells. After 36 hr, cells were treated with 50 ng/ml Wnt-3a and 25 nM MG132 for 6 hr. Cell lysates were subjected to IP with Flag antibody followed by IB with HA or FoxM1 antibody.",
    "ncbi_link": "FoxM1: 2305
USP5: 8078"
  },
  {
    "caption": "F. FoxM1 siRNA or control siRNA was transfected into U87 cells, lysates were subjected to IP with β-catenin antibody, followed by IB with β-catenin, ICAT, FoxM1 or IgG antibodies.",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "G. ICAT siRNA or control siRNA was transfected into LN229 cells, lysates were subjected to IP with β-catenin antibody, followed by IB with β-catenin, ICAT, FoxM1 or IgG antibodies.",
    "ncbi_link": "ICAT: 56998"
  },
  {
    "caption": "H. ChIP analyses of endogenous β-catenin binding at the TCF-binding site of the Axin2 promoter were performed in vector-, FoxM1- or/and ICAT plasmid-transfected U87 cells. Fold was calculated relative to that in cells transfected with the vector, which was set as 1.",
    "ncbi_link": "Axin2: 8313"
  },
  {
    "caption": "I. ChIP analyses of endogenous β-catenin binding at the TCF-binding site of the Axin2 promoter were performed in FoxM1 siRNA-, ICAT siRNA-, control siRNA- or combination of FoxM1 siRNA and ICAT siRNA-transfected U87 cells as described in (H).",
    "ncbi_link": "Axin2: 8313
ICAT: 56998
FoxM1: 2305"
  },
  {
    "caption": "J. ChIP analyses of endogenous β-catenin binding at the TCF-binding site of the Axin2 promoter were performed in vector-, β-catenin-NLS-, sh-FoxM1-, FoxM1-shR- and/or ICAT plasmid-transfected U87 cells as described in (H).",
    "ncbi_link": "Axin2: 8313
β-catenin: 1499
ICAT: 56998
FoxM1: 2305"
  },
  {
    "caption": "A. FoxM1 or/and ICAT plasmids were co-transfected with Axin-2 promoter luciferase and TK-Renilla plasmid into U87 cells. Luciferase activity was measured with the Dural Luciferase reporter assay, and relative luciferase activity was normalized to that of the vector group. Values are mean ± SD for triplicate samples.",
    "ncbi_link": "luciferase: 
TK-Renilla: 
Axin-2: 8313"
  },
  {
    "caption": "B. FoxM1 siRNA#1, #2 or control siRNA were co-transfected to U87 cells with Axin-2 promoter reporter. Luciferase activity was measured with the Dural Luciferase reporter assay, and relative luciferase activity was normalized to that of the control siRNA group. Values are mean ± SD for triplicate samples.",
    "ncbi_link": "luciferase: 
Axin-2: 8313"
  },
  {
    "caption": "C. ICAT siRNA or control siRNA were co-transfected into LN229 cells with Axin-2 promoter reporter. Luciferase activity was measured as in (C).",
    "ncbi_link": "Luciferase: 
Axin-2: 8313"
  },
  {
    "caption": "D. FoxM1 or/and ICAT plasmids were co-transfected with TOP-Flash reporter and TK-Renilla plasmids into U87 cells. Luciferase activity of TOP-Flash in the cells was measured as in A. Values are mean ± SD for triplicate samples.",
    "ncbi_link": "Luciferase: 
TK-Renilla: 
TOP-Flash: "
  },
  {
    "caption": "E. ICAT, FoxM1 or FoxM1-∆FB (FoxM1 mutant lacking the forkhead box domain) plasmid or their combinations were co-transfected with TOP-Flash reporter and TK-Renilla plasmids into LN229 cells. Luciferase activity of TOP-Flash in the cells was measured as in A. Values are mean ± SD for triplicate samples.",
    "ncbi_link": "Luciferase: 
TK-Renilla: 
TOP-Flash: "
  },
  {
    "caption": "F. FoxM1 siRNA and/or ICAT siRNA were co-transfected with TOP-Flash reporter and TK-Renilla plasmids into LN229 cells, and the cells were treated with Wnt3a (50 ng/ml) or control PBS. Luciferase activity of TOP-Flash in the cells was measured as in A. Values are mean ± SD for triplicate samples.",
    "ncbi_link": "Luciferase: 
TK-Renilla: 
TOP-Flash: 
ICAT: 56998
FoxM1: 2305"
  },
  {
    "caption": "G. Vector-, β-catenin-NLS-, sh-FoxM1-, FoxM1-shR- and/or ICAT plasmids were co-transfected with TOP-Flash reporter and TK-Renilla plasmids into U87 cells. Luciferase activity of TOP-Flash in the cells was measured as in (A). Values are mean ± SD triplicate samples.",
    "ncbi_link": "Luciferase: 
TK-Renilla: 
TOP-Flash: 
β-catenin: 1499
FoxM1: 2305"
  },
  {
    "caption": "B. LN229 cells were transfected with vector control, FoxM1, FoxM1 plus sh-β-catenin or FoxM1 plus ICAT plasmid. The proliferation percentage was determined as described in (A).",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "C. LN229-shFoxM1 cells were transfected with FoxM1-shR (siRNA-resistant FoxM1), or FoxM1-shR plus ICAT plasmid. The cells were then treated with Wnt3a (50 ng/ml). The proliferation percentage was determined as described in (A).",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "D. LN229 cells were transfected with USP5 and/or FoxM1 siRNA. The proliferation percentage was determined as described in (A).",
    "ncbi_link": "FoxM1: 2305
USP5: 8078"
  },
  {
    "caption": "E. LN229 cells were transfected with USP5 siRNA and/or FoxM1 plasmid. The cells were then treated with Wnt3a (50 ng/ml). The proliferation percentage was determined as described in (A). Data shown in (A)-(E) represent the mean ± SD of three independent experiments.",
    "ncbi_link": "USP5: 8078"
  },
  {
    "caption": "I-J. Axin2 mRNA levels in the above 50 GBM specimens were examined through RNAscope technology. The staining was scored as 1-12 according to the intensity and percentage. The significance of the correlations was determined by Pearson's correlation test.",
    "ncbi_link": "Axin2: 8313"
  },
  {
    "caption": "(A) ADAR2 is most strongly expressed in vascular tissues. Graph showing ADAR2 gene expression data derived from GTEx for few representative human tissues. Note the highest expression of ADAR2 in the tibial artery followed by colon and esophagus. Boxes represent the 25th and the 75th percentile with median represented by the black line in the box. The whiskers depict the minimum and the maximum value.",
    "ncbi_link": "ADAR2: 104"
  },
  {
    "caption": "(B) FLNA gene expression in few representative human tissues from >500 different donors using GTEx data. Tibial artery, colon and esophagus show highest gene expression similar to ADAR2 expression. Boxes represent the 25th and the 75th percentile with median represented by the black line in the box. The whiskers depict the minimum and the maximum value.",
    "ncbi_link": "ADAR2: 104
FLNA: 2316"
  },
  {
    "caption": "(C) Bar graph shows FLNA RNA editing (%) among few representative human tissues. Note very high editing levels in the arterial system (red bars).",
    "ncbi_link": "FLNA: 2316"
  },
  {
    "caption": "(D) Scatter plot shows the log fold change in editing levels of several candidates between ventricles of healthy donors and heart samples of cardiomyopathy patients. FLNA marked in the graph is one significant discriminator. Y axis is the -log 10 of the p value for the difference between healthy and sick. The colors (red vs green) reflect the threshold cutoffs randomly assigned to distinguish the sites, which demonstrate large, highly significant differences between the two groups. Fold change cutoff of 0.9 was used.",
    "ncbi_link": "FLNA: 2316"
  },
  {
    "caption": "(E) Scatter plot shows the FLNA RNA editing in control and diseased human tibial arteries and aorta. At least 4 control and 7 diseased human donors were used in each case. P value <0.05 measured by t test was considered significant.",
    "ncbi_link": "FLNA: 2316"
  },
  {
    "caption": "(A) Scheme showing the FLNA wild-type (wt) allele, the targeting vector and the FLNAΔECS neo-allele. The loxP flanked PGK-neo cassette in the targeting vector replaced the editing complementary sequence (ECS) using homologous recombination, which was then deleted using Cre recombinase. Right, southern blotting analysis screened for positive clones shown. The positions of loxP sites, restriction enzyme (EcoRI) and Southern blotting probe are also indicated.",
    "ncbi_link": "PGK: 
Cre recombinase: 2777477
FLNA: 192176"
  },
  {
    "caption": "(B) Sequencing electropherograms show the average FLNA editing levels in wt and FLNAΔECS tissues (Stomach, colon, heart, lung and tibial artery). Editing levels were checked in tissues from 3 independent mice and the value below the chromatogram depict the average value of 3 replicates. Data information: Arrows indicate the FLNA editing site.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(C) FLNA mRNA expression levels measured by qPCR in wt and FLNAΔECS colon tissue showed no difference. Data information: data shown as mean ± SD from three independent experiments. ** P<0.05",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(D) FLNA protein levels measured by western blotting are identical in wt and FLNAΔECS stomach tissue. Y-axis represents FLNA expression normalized to tubulin levels. Data information: data shown as mean ± SD from three independent experiments. ** P<0.05",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(E) FLNA editing levels (%) in wt whole dorsal aorta, tunica media and tunica adventitia. Tunica media consisting of smooth muscle cells show the highest FLNA RNA editing. Data information: Arrows indicate the FLNA editing site. data shown as mean ± SD from three independent experiments. ** P<0.05",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "A,B) Treatment of aortic rings with thromboxane A2 receptor agonist U46619 leads to (A) hypercontraction and (B) increased contraction force in FLNAΔECS aortae in myograph chambers. Emax was higher in FLNAΔECS aortae without any difference in EC50 as compared to wt aortae. For each condition, 10-12 aortic rings from at least 4 wild-type (wt) and 4 FLNAΔECS mice were used. Data shown as mean ± SEM. * P<0.05, ** P<0.01, *** P<0.001 (Student's t test)",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(C) Graph shows the normalized cell contraction measured by Xcelligence Real time cell analyzer in wt (red) and FLNAΔECS (green) primary vascular smooth muscle cells (vSMC) indicating hypercontraction in FLNAΔECS cells in response to 10μM U46619. Data shown as mean ± SD from three independent experiments.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(D) Quantification of cell index measurements plotted as percentage of contraction following different concentrations of U46619. Data shown as mean ± SD from three independent experiments. P value <0.05 (Student's t test) was considered significant. The difference between wt and FLNAΔECS was significant at every concentration of U46619.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(A) Myosin light chain phosphorylation detected by a phospho-specific antibody (pMLC) and normalized to total myosin light chain (MLC). Tubulin served as a loading control. Quantification shows a significant increase in pMLC in FLNAΔECS vSMCs. Data information data shown as mean ± SD from at least three independent experiments. ** P<0.05 (Student's t test)",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(B) Rhotekin Pull down activation assay was performed on wt and FLNAΔECS vSMC lysates and activated (GTP) bound RhoA was compared between the 2 genotypes. FLNAΔECS vSMCs show more GTP-loaded RhoA than wt vSMCs. Tubulin was used as a loading control. Data information: data shown as mean ± SD from at least three independent experiments. ** P<0.05 (Student's t test)",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(C) Thromoboxane A2 stimulation with U46619 increased phosphorylation of myosin light chain phosphatase (pMYPT1) in FLNAΔECS vSMCs as shown by western blotting on vSMC lysates with phosphor-specific MYPT1 antibody. Data information: data shown as mean ± SD from at least three independent experiments. ** P<0.05 (Student's t test)",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(D) CPI17 phosphorylation levels were measured in wt and FLNAΔECS vSMCs in untreated cells and in the presence of ROCK and PKC inhibitor using pCPI17 antibody. Data information: data shown as mean ± SD from at least three independent experiments. ** P<0.05 (Student's t test)",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "A-C) Telemetry measurements were done on mice continuously for 72 hrs and reading was recorded every minute to analyse blood pressure in wt and FLNAΔECS mice. Scatter plots show diastolic blood pressure over 72 hrs (A), diastolic blood pressure during inactive phase (B) and diastolic pressure during active phase (C). Note: Significant increase in diastolic blood pressure in FLNAΔECS mice during the inactive phase. 9 mice (5 males marked as square + 4 females marked as round) were analyzed for each genotype. Data shown as mean ± SEM. P value <0.05 (Student's t test) was considered significant. Boxes represent the 25th and the 75th percentile with median represented by the black line in the box. The whiskers depict the minimum and the maximum value.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(A) Dorsal aortae were fixed, cross-sectioned and then stained with Elastica van Gieson stain to visualize collagen around the blood vessel. 6 independent mice (5-6 months) of each genotype were used for the analysis. Scale bar: 50 μm. (B) Plot shows individual data points (black-wt, red-mutant) of adventitial area in both the genotypes. Measurements show increased adventitial area in FLNAΔECS aortae. P value <0.05 was considered significant (Student's t test) ",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(C) Representative heart sections of a 5-6 months old mice stained with Masson Trichrome shows increased collagen (blue) around coronary vessels (marked by arrowheads) Scale bar: 50 μm. (D) Quantification shows a significant increase in perivascular fibrosis in FLNAΔECS hearts. Four sections from each heart were measured. Four mice analyzed for each genotype. P value <0.05 considered significant. (mixed model approach) ",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(E) Representative longitudinal heart sections stained with H&E staining (RV: right ventricle, LV: left ventricle). Black lines represent thickness of interventricular (IVS) and lateral left ventricular wall (LLVH). Scale bar: 1mm. (F) Scatter graph shows increased ventricular wall thickness in FlnAΔECS mice hearts. Six male mice (6months old) analyzed for each genotype. P value <0.05 was considered significant. (Student's t test)",
    "ncbi_link": "FlnA: 2316"
  },
  {
    "caption": "(A) Graph showing the individual blood velocity profile determined by MRI over time in 4 wt mice (shades of grey) and 5 FLNAΔECS mice (shades of red). The mouse shown in dotted purple line is clearly an outlier within the FLNAΔECS cohort. Aortic velocity waveform represents velocity during different stages of cardiac cycle. A significant reduction of velocity was observed at 40ms in the systolic cycle.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": "(B) Representative wt (top) and FLNAΔECS (below) mouse showing the blood flow just above the aortic valve. Note: Reduced blood flow in FLNAΔECS mouse as depicted by pseudocoloring. The red circle represents the time window at which the images are shown.",
    "ncbi_link": "FLNA: 192176"
  },
  {
    "caption": " (D) Flow cytometry analysis of CD34+CD1a- thymocytes submitted to FTOC with fetal thymic lobes deficient for Dll4 and/or Jag2 (Cre+) as indicated above the dot plots. Numbers in dot plots indicate percentage of cells for the corresponding populations. Histograms show TCRγδ expression in CD3+TCRαβ+ (blue) and CD3+TCRαβ- (red) cells. (E, F) (E) Mean frequency and (F) absolute cell numbers of CD3+TCRαβ+ (blue) and CD3+TCRγδ+ (red) thymocytes developed in corresponding cultures from D (n=5-7 independent experiments, depending on the mouse genotype, error bars indicate SEM and * indicates p<0.05 and ns (not significant) indicates p>0.05 in a non-parametric Mann-Whitney U test). ",
    "ncbi_link": "Cre: 2777477
Dll4: 54485
Jag2: 16450"
  },
  {
    "caption": "(A) Line plots displaying averaged NOTCH1, MYC and HES1 expression across T cell development (n=2 biological replicates and error bars indicate SEM).",
    "ncbi_link": "HES1: 3280
MYC: 4609
NOTCH1: 4851"
  },
  {
    "caption": " (B) Heatmap displaying transcript wise scaled expression of NOTCH1, HES1, MYC and miRNAs from ex vivo isolated subsets correlating (spearman rho >= 0.5) with NOTCH1 gene expression Red arrows indicate all 6 members of the miR-17~92 cluster (n=2). ",
    "ncbi_link": "HES1: 3280
miR-17: 407975
MYC: 4609
NOTCH1: 4851"
  },
  {
    "caption": " (C) Heatmap visualizing Notch1 regulated gene expression of in vitro cultured thymocytes across multiple culturing conditions (OP9-control, OP9-JAG1, OP9-JAG2, OP9-DLL1 and OP9-DLL4) and time points (day 0, 5 and 10). ",
    "ncbi_link": "DLL1: 13388
DLL4: 54485
JAG1: 16449
JAG2: 16450
Notch1: 4851"
  },
  {
    "caption": "(D) NOTCH1 correlating miRNAs (spearman rho >= 0.3) of in vitro cultured thymocytes across multiple culturing conditions and timepoints. The miRNA expression levels were scaled transcript wise and red arrows indicate members of miR-17~92 cluster (n=2).",
    "ncbi_link": "NOTCH1: 4851"
  },
  {
    "caption": "(E) CHIPseq data for Notch1 and RBPj binding at the miR-17~92 locus in CUTTL1 cells. Red line underneath the ChIPseq peaks indicate significant enrichment compared to the input sample.",
    "ncbi_link": "miR-17: 407975"
  },
  {
    "caption": "(B) Transfection of miR-17 Pre-miR miRNA Precursor, but not of miR-92a, specifically targets the wild-type (black bars) 3'UTR of BCL11B in a 3'UTR luciferase reporter assay following cotransfection of HEKT cells in comparison to the controls (transfection of no miRNA or a control miRNA). Mutation of the predicted miR-17 binding sites in the 3'UTR BCL11B reporter construct prevents miR-17 dependent targeting (grey bars). Graphs show mean firefly luciferase values (from 3'UTR reporter constructs) following normalization to the cotransfected control Renilla luciferase and relative to control sample without miRNA (n=5 independent experiments, error bars indicate SEM and * indicates p<0.05 and ns (not significant) indicates p>0.05 in a paired t-test).",
    "ncbi_link": "luciferase: 
BCL11B: 64919
miR-17: 407975
miR-92a: 407975"
  },
  {
    "caption": " (C) Quantitative RT-PCR gene expression analysis of BCL11B in control (black bar) or miR-17 (grey bar) transduced CD34+ thymocytes after 24h of culture on coated Fc-DLL1 plates, relative to the geometric mean of ACTIN and GAPDH and relative to the control-transduced sample (n=3 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
DLL1: 13388
GAPDH: 2597
miR-17: 407975"
  },
  {
    "caption": " (D) Quantitative real-time RT-PCR gene expression analysis of BCL11B in control (black bar) or miR-17 sponge (white bar) transduced CD34+ thymocytes, relative to the geometric mean of ACTIN and GAPDH (n=5 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
GAPDH: 2597
miR-17: 407975"
  },
  {
    "caption": " (A) Gene expression pattern of BCL11B (red dots) and HES1 (blue squares) during human T cell development, derived from microarray data as shown in Figure 2. (n=2 biological replicates and error bars indicate SEM). ",
    "ncbi_link": "BCL11B: 64919
HES1: 3280"
  },
  {
    "caption": " Quantitative RT-PCR expression analysis of BCL11B in human after 5 days, respectively, of coculture on OP9 stromal cells expressing different Notch ligands. Graphs show mean expression, relative to the geometric mean of ACTIN and GAPDH and relative to the OP9-DLL1 cultured cells (n=4 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 and ns (not significant) indicates p>0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
DLL1: 13388
GAPDH: 2597"
  },
  {
    "caption": " Quantitative RT-PCR expression analysis of BCL11B in human CD34+ thymocyte progenitors after 2 days, respectively, of coculture on OP9 stromal cells expressing different Notch ligands. Graphs show mean expression, relative to the geometric mean of ACTIN and GAPDH and relative to the OP9-DLL1 cultured cells (n=4 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 and ns (not significant) indicates p>0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
DLL1: 13388
GAPDH: 2597"
  },
  {
    "caption": " (D) Quantitative RT-PCR expression analysis of BCL11B in human CD34+ thymocyte progenitors after 2 days of coculture on OP9-DLL1 stromal cells in the presence of 5 µM DAPT (GSI). Graphs show mean expression, relative to the geometric mean of ACTIN and GAPDH and relative to sample cultured in the presence of control DMSO (n=4 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
DLL1: 13388
GAPDH: 2597"
  },
  {
    "caption": " Quantitative RT-PCR expression analysis of miR-17 in human CB CD34+Lin- after 5 days, respectively, of coculture on OP9 stromal cells expressing different Notch ligands Graphs show mean expression, relative to the geometric mean of SNORD61, SNORD95 and RNU6-2 and relative to the OP9-DLL1 cultured cells (n=2 independent experiments with different donors; error bars indicate SEM - the two data points are shown). ",
    "ncbi_link": "DLL1: 13388
miR-17: 407975
RNU6-2: 103625684
SNORD61: 26787
SNORD95: 619570"
  },
  {
    "caption": " Quantitative RT-PCR expression analysis of miR-17 in human CD34+ thymocyte progenitors after 5 and 2 days, respectively, of coculture on OP9-DLL1 stromal cells in the presence of 5 µM DAPT (GSI). Graphs show mean expression, relative to the sample cultured in the presence of control DMSO (F) (n=2 independent experiments with different donors; error bars indicate SEM - the two data points are shown). ",
    "ncbi_link": "DLL1: 13388
miR-17: 407975"
  },
  {
    "caption": " (G) Quantitative RT-PCR gene expression analysis of BCL11B in control (black bar), GATA3 shRNA or TCF7 shRNA (grey bars) transduced CD34+ thymocytes after 48h of coculture on OP9-DLL1 stromal cells, relative to the geometric mean of ACTIN and GAPDH and relative to the control-transduced sample (n=6 independent experiments with different donors for GATA3 shRNA, n=4 independent experiments with different donors for TCF7 shRNA, error bars indicate SEM and * indicates p<0.05 in a paired t-test). ",
    "ncbi_link": "ACTIN: 
BCL11B: 64919
DLL1: 13388
GAPDH: 2597
GATA3: 2625
TCF7: 6932"
  },
  {
    "caption": " (A) Flow cytometry analysis of control and miR-17 transduced CD34+ thymocytes, cultured in ATOs for 3 weeks. Numbers in contour plots indicate percentage of cells for the corresponding populations. Histograms show TCRγδ expression in CD3+TCRαβ+ (blue) and CD3+TCRαβ- (red) cells. (B) Graphs show the mean frequency of CD4+CD8β+ DP, CD3+TCRαβ+ and CD3+TCRγδ+ thymocytes of control (black bar) or miR-17 (grey bar) transduced CD34+ thymocytes in these cultures (n=6 and n=8 independent experiments for control and miR-17, respectively. Error bars indicate SEM and ns (not significant) indicates p>0.05 in a non-parametric Mann-Whitney U test). (C) Graphs show the mean absolute cell numbers of total, CD4+CD8β+ DP, CD3+TCRαβ+ and CD3+TCRγδ+ thymocytes that developed in these cultures (n=6 and n=8 independent experiments for control and miR-17, respectively. Error bars indicate SEM and * indicates p<0.05 in a non-parametric Mann-Whitney U test). ",
    "ncbi_link": "miR-17: 407975"
  },
  {
    "caption": "(A) Flow cytometry analysis showing mean of Median Fluorescence Intensity (MFI) of BCL11B protein levels in Jurkat cells, 72h post transduction with control shRNA (black bar), BCL11B shRNA1 or BCL11B shRNA2 (grey bars), each normalized to the FMO sample (BCL11B stained - BCL11B unstained sample). (n=2 independent experiments; error bars indicate SEM - the two data points are shown).",
    "ncbi_link": "BCL11B: 64919"
  },
  {
    "caption": " (C) Mean total cell numbers of control shRNA (black bar), BCL11B shRNA1 or BCL11B shRNA2 (grey bars) transduced CD34+ thymocytes, cultured in ATOs for 3 weeks (n=5 independent experiments with different donors, error bars indicate SEM and * indicates p<0.05 in a non-parametric paired Wilcoxon test). ",
    "ncbi_link": "BCL11B: 64919"
  },
  {
    "caption": "(A, B) Inhibition of autophagy by dominant‐negative (DN) TAK1. HeLa cells were co‐transfected with a GFP-LC3‐encoding construct plus pcDNA3.1 (empty vector), or plasmids for the expression of WT TAK1 (TAK1WT) or the DN TAK1K63W mutant. One day later, cells were either left untreated (control) or driven into autophagy by starvation or by the administration of 1 μM rapamycin or 30 μM pifithrin α (PFTα), followed by immunoblotting for the detection of TAK1 and endogenous LC3 (A) or immunofluorescence microscopy for the quantification of cells with cytosolic GFP-LC3 puncta (GFP-LC3VAC cells) (B) (mean values±s.d., n=3; *P0.01 versus control cells). GAPDH levels were monitored to ensure equal loading.",
    "ncbi_link": "LC3: 440738///81631///84557
TAK1: 6885"
  },
  {
    "caption": "(C, D) Inhibition of autophagy by knockdown of VPS34, Beclin 1 (BCN1) and TAK1. siRNAs that effectively deplete VPS34, BCN1 and TAK1 were co‐transfected with a GFP-LC3‐encoding plasmid in HeLa cells. Autophagy was then induced as in (A) and the frequency of GFP-LC3VAC cells (mean values±s.d., n=3; *P0.01 versus control cells) was determined.",
    "ncbi_link": "BCN1: 8678
Beclin 1: 8678
LC3: 440738///81631///84557
TAK1: 6885
VPS34: 5289"
  },
  {
    "caption": "(A, B) Detection of autophagic GFP-LC3+ puncta. HeLa or U2OS cells stably expressing GFP-LC3 were transfected with siRNAs targeting TAK1, TAB1, TAB2 or TAB3 or with a control siRNA (siUNR). One day later, the subcellular localization and abundance of GFP-LC3 or immunostained TAB2 or TAB3 was determined by epifluorescence microscopy. Representative images are shown in (A) (HeLa cells) and quantitative results (mean values±s.d., n=3; *P0.01 versus siUNR‐transfected cells) are depicted in (B) (U2OS cells).",
    "ncbi_link": "LC3: 440738///81631///84557
TAK1: 6885
TAB1: 10454
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(C) Lipidation of LC3 induced by TAB2 or TAB3 knockdown. Representative immunoblots showing the conversion of non‐lipidated LC3 (LC3‐I) to its lipidated variant (LC3‐II) as well as SQSTM1/p62 protein levels are shown. GAPDH levels were monitored to ensure equal loading.",
    "ncbi_link": "LC3: 440738///81631///84557
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(D, E) Quantification of autophagosomes and autophagolysosomes by transmission electron microscopy. Representative images of HeLa cells transfected with siUNR or with TAB2‐ or TAB3‐targeting siRNAs are shown in (D), and quantitative results are depicted in (E) (mean values±s.d., n=3; *P0.01 versus siUNR‐transfected cells).",
    "ncbi_link": "TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(F) Epistatic analysis of the effects of TAB2 and TAB3 depletion on autophagy. HeLa cells stably expressing GFP-LC3 were transfected with siRNAs specific for TAB2 or TAB3 and/or with cDNAs coding for full‐length HA‐tagged TAB2 (HA-TAB2) or TAB3 (HA-TAB3). Twenty‐four hours later, the frequency of cells exhibiting >5 GFP-LC3+cytosolic puncta (GFP-LC3VAC cells) was determined. Results are mean values±s.d. (n=3; *P0.01 versus siUNR‐transfected cells).",
    "ncbi_link": "LC3: 440738///81631///84557
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(G) U2OS cells stably expressing FYVE-RFP were transfected with siUNR, or with siRNAs specific for TAB2, TAB3, VPS34, Beclin 1 (BCN1) and TAK1, in the indicated combinations. Forty‐eight hours later, the percentage of cells with RFP-FYVE+ puncta cells was determined. Results are mean values±s.d. (n=3; *P0.01 versus siUNR‐transfected cells).",
    "ncbi_link": "BCN1: 8678
Beclin 1: 8678
TAK1: 6885
VPS34: 5289
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(A-D) Impact of bafilomycin A1 (BafA1) on the induction of GFP-LC3+ puncta by TAB2 and TAB3 depletion. HeLa cells stably expressing GFP-LC3 were transfected with a control siRNA (siUNR) or with siRNAs targeting TAB2 and TAB3 for 24 h. During the last 12 h of this period, BafA1 was optionally added. After fixation and permeabilization, LAMP2 was detected by immunofluorescence. Representative confocal microphotographs for the TAB2 siRNA are shown (A), together with the profiles of colocalization of fluorescent signals (B) along the indicated direction (α-ω). Columns in (C) represent the percentage of colocalization of GFP-LC3 and LAMP2 (mean values±s.d.; *P0.01 versus siUNR‐transfected cells), as quantified in at least 50 cells for each condition. The frequency (mean±s.d.) of cells with >5 GFP-LC3+cytosolic puncta (GFP-LC3VACcells) is plotted in (D).",
    "ncbi_link": "LC3: 440738///81631///84557
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(F, G) Impact of autophagy‐relevant proteins and of the TAK1‐IKK signalling axis on GFP-LC3 aggregation induced by the depletion of TAB2 or TAB3. HeLa cells stably expressing GFP-LC3 were transfected with siUNR or with siRNAs targeting the indicated proteins, alone or in combination, and 48 h later GFP-LC3VAC cells were quantified (mean values±s.d., n=4; *P0.01 versus siUNR‐transfected cells).",
    "ncbi_link": "LC3: 440738///81631///84557
TAK1: 6885
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(H) Inhibition of autophagy by dominant‐negative (DN) TAK1. HeLa cells stably expressing GFP-LC3 were co‐transfected with pcDNA3.1 (empty vector) or with plasmids encoding WT (TAK1WT) or a DN TAK1 variant (TAK1K63W) together with the indicated siRNAs for 24 h, followed by the quantification of GFP-LC3VAC cells (mean values±s.d., n=3, *P0.01 versus siUNR‐, pcDNA3.1‐transfected cells)",
    "ncbi_link": "LC3: 440738///81631///84557
TAK1: 6885"
  },
  {
    "caption": "(A) Effects of full‐length TAB2 and TAB3 or their deletion mutants (as in Figure 1C) on autophagy. HeLa cells stably expressing GFP-LC3 were transfected with pcDNA3.1 (empty vector) or with plasmids encoding the indicated TAB2 and TAB3 variants for 24 h, then driven into autophagy by starvation or by the administration of 1 μM rapamycin or 30 μM pifithrin α (PFTα) for 4 h. Finally, the frequency (mean±s.d., n=3) of cells with >5 GFP-LC3+cytosolic puncta (GFP-LC3VAC cells) was assessed (*P0.01 versus control cells transfected with the same plasmid; #P0.01 versus pcDNA3.1‐transfected cells treated with the same pro‐autophagic trigger).",
    "ncbi_link": "LC3: 440738///81631///84557
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(B) U2OS cells stably expressing FYVE-RFP were co‐transfected with pcDNA3.1 or with vectors encoding TAB2C or TAB3C together with a control siRNA (siUNR) or with siRNAs specific for VPS34, Beclin 1 (BCN1) or TAK1 for 24 h, followed by the quantification of cells exhibiting FYVE-RFP+ dots (FYVE-RFP+). Results are mean values±s.d. (n=3; *P0.01 versus siUNR‐, pcDNA3.1‐transfected cells).",
    "ncbi_link": "FYVE: 
BCN1: 8678
Beclin 1: 8678
TAK1: 6885
VPS34: 5289
TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(C) Inhibition of the interaction between endogenous TAB2, TAB3 and BCN1 by C‐terminal fragments of TAB2 and TAB3. Forty‐eight hours after transfection with pcDNA3.1 or plasmids coding for the indicated proteins, cells were lysed, TAB2 or TAB3 was immunoprecipitated and BCN1 was immunodetected. GAPDH levels were monitored to ensure equal loading. This experiment has been done three times, yielding comparable results.",
    "ncbi_link": "TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(D) Mechanisms of autophagy induction by the Beclin‐binding domain (BBD)‐containing C‐terminal fragments of TAB2 and TAB3. HeLa cells were transfected with pcDNA3.1, TAB2C‐ or TAB3C‐encoding plasmids in combination with the indicated siRNAs for 24 h, followed by the quantification of GFP-LC3VAC cells (mean values±s.d., n=3; *P0.01 versus siUNR‐, pcDNA3.1‐transfected cells).",
    "ncbi_link": "TAB2: 23118
TAB3: 257397"
  },
  {
    "caption": "(D, E) Inhibition of the interaction between endogenous BCN1, TAB2 and TAB3 by a BCN1 fragment corresponding to the TBD. HeLa cells were transfected with pcDNA3.1 (empty vector) or with plasmids encoding the TBD or a His-tagged Beclin 1 variant lacking the TBD (His-BCN1ΔTBD), followed by co‐immunoprecipitation of endogenous TAB2 (D) or TAB3 (E) and detection of BCN1.",
    "ncbi_link": "BCN1: 8678
Beclin 1: 8678"
  },
  {
    "caption": "(F) Induction of autophagy by the TBD. HeLa cells stably expressing GFP-LC3 were transfected with pcDNA3.1 or constructs encoding the indicated BCN1 variants. After 24 h, Flag‐tagged proteins were detected by immunoblotting and the frequency of cells with >5 GFP-LC3+cytosolic puncta (GFP-LC3VAC cells) was assessed (mean values±s.d., n=3; *P0.01, **P0.001 versus pcDNA3.1‐transfected cells).",
    "ncbi_link": "BCN1: 8678
LC3: 440738///81631///84557"
  },
  {
    "caption": "(G, H) Mechanisms of autophagy induction by the TBD. (G) U2OS cells stably expressing RFP-FYVE were transfected pcDNA3.1 or plasmids for the expression of TBD, BCN1 or BCN1ΔTBD in combination with a control siRNA (siUNR) or siRNAs that effectively deplete VPS4, BCN1 and TAK1. Forty‐eight hours later, the percentage of cells exhibiting FYVE-RFP+ dots (FYVE-RFP+) was assessed. (G). Alternatively, HeLa cells stably expressing GFP-LC3 were transfected with pcDNA3.1 or with a TBD‐encoding plasmids plus siUNR or siRNAs specific the indicated proteins. Forty‐eight hours later, the percentage of GFP-LC3VAC cells was determined (H). Results are mean values±s.d. (n=3, *P0.01 versus siUNR‐, pcDNA3.1‐transfected cells).",
    "ncbi_link": "FYVE: 
BCN1: 8678
LC3: 440738///81631///84557
TAK1: 6885
VPS4: 27183"
  },
  {
    "caption": "(I) Inhibition of TBD‐induced autophagy by dominant‐negative (DN) TAK1. Cells were co‐transfected pcDNA3.1 or vectors encoding WT TAK1 (TAK1WT) or a DN TAK1 variant (TAK1K63W) alone or together with a TBD‐encoding plasmid for 24 h, followed by the quantification of GFP-LC3VAC cells (mean values±s.d., n=3; *P0.01 versus pcDNA3.1‐transfected cells).",
    "ncbi_link": "TAK1: 6885"
  },
  {
    "caption": "(A) Examples of chromosome arms exhibiting features of telomeric semiconservative (Semi) replication, conservative (Consrv) replication of the entire telomere (E) and conservative replication of part of the telomere (P). Idealized chromosome diagrams (left) and actual microscopy images (right) are shown. D-FISH, denaturing FISH; ND-CO-FISH (non-denaturing CO-FISH).(B) Percentages of chromosome arms exhibiting conservative (Consrv) replication of the entire telomere (E), conservative replication of part of the telomere (P) and conservative replication of either the entire telomere of part of it (E+P). NE, U2OS cells expressing normal levels of cyclin E; OE, U2OS cells overexpressing cyclin E for four days. Bars represent means and standard errors of the mean from three independent experiments. Cyclin E overexpression resulted in higher percentages of conservatively replicated telomeres: P<0.025 for Consrv (P) and P<0.05 for Consrv (E+P), as calculated using the paired t test.",
    "ncbi_link": "cyclin E: 898
Cyclin E: 898"
  },
  {
    "caption": "(A) Decrease in the fraction of chromosome arms exhibiting conservative (Consrv) DNA replication of the entire telomere length or part of the telomere (E+P) in U2OS cells after depletion of POLD3 or POLD4 by siRNA. si Ctrl, control siRNA; NE, cells expressing normal levels of cyclin E; OE, cells overexpressing cyclin E for four days. Bars represent means and standard errors of the mean from two independent experiments. For statistical comparisons the effects of PolD3 and Pold4 depletion were examined after grouping together the data from the NE and OE cells. PolD3 depletion reduced the fraction of conservatively replicated telomeres at a level of P=0.072; whereas for PolD4 depletion the decrease was significant at a level of P<0.025, as calculated using the paired t test.(B) Decreased telomere length following PolD3 or PolD4 depletion in U2OS cells expressing normal levels of cyclin E (NE) or overexpressing cyclin E (OE). The cells were transfected with control siRNA (si Ctrl) or siRNAs targeting POLD3 or POLD4 and, five days later, fixed and examined for telomere length by Q-FISH. Bars indicate means and standard error of the mean from more than 2,600 telomeres examined per condition. The differences between control and PolD3 or PolD4-depleted cells were significant (P<10-6) for both NE and OE cells, as determined by unpaired t tests.",
    "ncbi_link": "cyclin E: 898
POLD3: 10714
PolD3: 10714
POLD4: 57804
Pold4: 57804
PolD4: 57804"
  },
  {
    "caption": "(C) Decreased telomere length following PolD3 or PolD4 depletion in parental U2OS cells. The cells were transfected with control siRNA (si Ctrl) or siRNAs targeting POLD3 or POLD4 and, five days later, fixed and examined for telomere length by Q-FISH. Bars indicate means and standard error of the mean from more than 2,800 telomeres examined per condition. The differences between control and PolD3 or PolD4-depleted cells were significant (P<10-6), as determined by unpaired t tests.",
    "ncbi_link": "PolD3: 10714
POLD3: 10714
PolD4: 57804
POLD4: 57804"
  },
  {
    "caption": "(D) Increased frequency of chromosome end-to-end fusions following POLD3 or POLD4 depletion. U2OS cells expressing normal levels of cyclin E (NE) or overexpressing cyclin E for four days (OE) were transfected with control siRNA (siCtrl) os siRNAs targeting POLD3 or POLD4. For each condition, 25 metaphases were examined (representing about 1,900 high quality chromosome arms per condition); the percentage of chromosome fusions was determined for each metaphase and used to calculate means and standard errors of the mean. For statistical analysis, the number of chromosome end-to-end fusions were compared by chi square tests among the various conditions. Cyclin E overexpression led to a higher number of fusions (P<0.0005); PolD3 and PolD4 depletion also led to a higher number of fusions (P<0.001 and P<0.025, respectively).",
    "ncbi_link": "cyclin E: 898
Cyclin E: 898
POLD3: 10714
PolD3: 10714
POLD4: 57804
PolD4: 57804"
  },
  {
    "caption": "E. Whole lysates of cells KYSE150 and KYSE150HSPH1-/- cells exposed to the indicated temperature conditions (aTT scheme and heat shock) were fractionated into  soluble and  insoluble fractions as described in Materials and Methods. Insoluble fractions were assayed for the level of K48-linked polyubiquitin  (left panel). Total levels of  HSPA1 and HSPH1 are shown for reference. K48 ubiquitin signals were quantified and displayed in a bar graph (means +/- SD, n = 4).",
    "ncbi_link": "HSPH1: 10808"
  },
  {
    "caption": "F. Lysates of cells KYSE150 and  KYSE150HSPH1-/- cells exposed to the indicated temperature conditions (aTT scheme and heat shock) were obtained and polysomes were isolated by centrifugation through a 30% sucrose cushion. Whole cell lysates (left panel) and the polysomal pellets (right panel) were assayed by immunoblotting for the levels of HSPH1, HSPA1 and proteasome subunits.",
    "ncbi_link": "HSPH1: 10808"
  },
  {
    "caption": "C. Kaplan-Meier plots showing the correlation between HSPH1 mRNA expression level and the survival of  patients with  ESCC. The expression data was obtained from and visualized with KM Plotter (www.kmplot.com, (Nagy et al, 2018) using the Pan Cancer algorithm at default settings.",
    "ncbi_link": "HSPH1: 10808"
  },
  {
    "caption": "D.  KYSE150  and KYSE150HSPH1-/- cells were injected into nude mice, and xenograft  tumor growth was monitored over time (left panel; mean tumor volume  +/- SEM, n = 4 with 5 animals per n). Mean tumor  weights at the end of the experiments were determined (means +/- SD, n = 4 with 5 animals  per n, number above the bar graph represent p values, * p<0.05, **p<0.01 (calculated with the two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli)).",
    "ncbi_link": "HSPH1: 10808"
  },
  {
    "caption": "(D-G) Quantitative real-time polymerase chain reaction analysis of miR-1a (D), miR-9 (E), miR-146a (F), and miR-155 (G) (n=4). RNA was isolated from pooled CSF (50 µl) from different mice (n=3). Data are displayed as mean ± SEM and analyzed by Student's t-test. Significance levels are indicated on the graphs: *, 0.01 ≤ P < 0.05; **, 0.001 ≤ P < 0.01.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(C-E) TaqMan qPCR assay for the quantification of miR-9 (C), miR-146a (D) and miR-155 (E) on the exosomal pellet isolated from conditioned medium of primary CPE cells grown in a transwell system and stimulated for 12 h with LPS (n=3).",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(F-I) Quantification of the miRNAs miR-1a (F), miR-9 (G), miR-146a (H) and miR-155 (I) by TaqMan qPCR assay from primary CPE cells grown in a transwell system without or with LPS stimulation (n=3). Significance levels are indicated on the graphs: *, 0.01 ≤ P < 0.05; **, 0.001 ≤ P < 0.01.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(B-D) TaqMan assay quantification of the miRNAs miR-9 (B), miR-146a (C) and miR-155 (D) in supernatant of LPS-stimulated primary CPE cells grown in a transwell system and either left untreated or pretreated with GW4869 to inhibit exosome secretion (n=3). miR-1a levels were below detection limit.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(E-H) TaqMan assay quantification of the miRNAs miR-1a (E), miR-9 (F), miR-146a (G) and miR-155 (H) in cell lysate of LPS-stimulated primary CPE cells grown in a transwell system left untreated or treated with GW4869 to inhibit exosome secretion (n=3). Data are displayed as mean ± SEM and analyzed by Student's t-test. Significance levels are indicated on the graphs: *, 0.01 ≤ P < 0.05; **, 0.001 ≤ P < 0.01.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(G-J) Quantitative real-time polymerase chain reaction (qPCR) analysis of miR-1a (G), miR-9 (H), miR-146a (I), and miR-155 (J). Data are presented as relative expression normalized with housekeeping miRs by TaqMan qPCR assay (0 h, n=4; 1 h, n=5; 6 h, n=5; 24 h, n=3).",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 387136///723959
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(L) qPCR analysis of the expression of miR-1a, miR-9, miR-146a and miR-155 in the choroid plexus of mice injected with LPS and then icv injected with vehicle (black) or GW4869 (grey), a neutral sphingomyelinase inhibitor that inhibits exosome secretion (n = 4).",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 387136///723959
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(D) qPCR analysis of the expression of miR-1a, miR-9, miR-146a and miR-155 in the choroid plexus of sham-operated mice (black) and mice subjected to CLP (grey) 10 hours after surgery. (E) qPCR analysis of the expression of miR-1a, miR-9, miR-146a and miR-155 in the CSF of sham-operated mice (black) and mice subjected to CLP (grey) 10 hours after surgery.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(G) qPCR analysis of the expression of miR-1a, miR-9, miR-146a and miR-155 in the choroid plexus of control mice (black) and in mice injected with TNF (grey) 6 hours after injection. (H) qPCR analysis of the expression of miR-1a, miR-9, miR-146a and miR-155 in the CSF of control mice (black) and on mice 6 hours after TNF injection (grey). Data are displayed as mean ± SEM and analyzed by Student's t-test. Scalebar 100 µm. Significance levels are indicated on the graphs: *, 0.01 ≤ P < 0.05; **, 0.001 ≤ P < 0.01; ***, 0.0001 ≤ P < 0.001.",
    "ncbi_link": "miR-146a: 387164
miR-155: 387173
miR-1a: 723959///387136
miR-9: 723968///723967///387133"
  },
  {
    "caption": "(A-B) qPCR gene expression analysis of miRNA target genes Mapk3, Notch1, Dicer, Tab2, Sox2, Calm2, Smad2, Smad5, Dnmt3 and Irak1 in mixed cortical cultures incubated with EVs isolated from CSF from untreated (black) or LPS treated (grey) mice (A) and in brain tissue (B) before (black) and 8 h after LPS injection (grey) (n=3).",
    "ncbi_link": "Calm2: 12314
Dicer: 192119
Dnmt3: 13436///13435
Irak1: 16179
Mapk3: 26417
Notch1: 18128
Smad2: 17126
Smad5: 17129
Sox2: 20674
Tab2: 68652"
  },
  {
    "caption": "(C) qPCR gene expression analysis of inflammatory genes Il-1β, Tnf, Il-6, iNos and iκbα by qPCR in mixed cortical cultures (left; in vitro) incubated with EVs isolated from CSF from untreated (black) or LPS treated (grey) mice and in brain tissue (right; in vivo) before (black) and 8 h after LPS injection (grey) (n=3).",
    "ncbi_link": "Il-1β: 16176
Il-6: 16193
iκbα: 18035
iNos: 18126
Tnf: 21926"
  },
  {
    "caption": "(E-F) qPCR gene expression analysis of inflammatory genes Il-1β, Tnf, Il-6, iNos and iκbα (E) and miRNA target genes Mapk3, Notch1, Dicer, Tab2, Sox2, Calm2, Smad2, Smad5, Dnmt3 and Irak1 (F) in mixed cortical cultures incubated with CD63-depleted EVs isolated from untreated mice (black) and mice treated with LPS for 6 h (grey) (n=3).",
    "ncbi_link": "Calm2: 12314
Dicer: 192119
Dnmt3: 13436///13435
Il-1β: 16176
Il-6: 16193
Irak1: 16179
Mapk3: 26417
iκbα: 18035
iNos: 18126
Notch1: 18128
Smad2: 17126
Smad5: 17129
Sox2: 20674
Tab2: 68652
Tnf: 21926"
  },
  {
    "caption": "(G-H) qPCR gene expression analysis of miRNA target genes Mapk3, Notch1, Dicer, Tab2, Sox2, Calm2, Smad2, Smad5, Dnmt3 and Irak1 (G) and inflammatory genes Il-1β, Tnf, Il-6, iNos and iκbα (H) in brain tissue from LPS-injected mice icv injected with vehicle (black) or GW4869 (grey; n=7). Data are displayed as mean ± SEM and analyzed by Student's t-test. Significance levels are indicated on the graphs: *, 0.01 ≤ P < 0.05.",
    "ncbi_link": "Calm2: 12314
Dicer: 192119
Dnmt3: 13436///13435
Il-1β: 16176
Il-6: 16193
Irak1: 16179
Mapk3: 26417
iκbα: 18035
iNos: 18126
Notch1: 18128
Smad2: 17126
Smad5: 17129
Sox2: 20674
Tab2: 68652
Tnf: 21926"
  },
  {
    "caption": "(A) Live imaging of Zp3-Cre Ndc80f/f oocytes injected with Ndc80-WT, Ndc80-9D or Ndc80-9A. Z-projection and 3D-reconstructed images show MTOCs (mNeonGreen-Cep192, green) and chromosomes (H2B-mCherry, magenta). Time in h:mm after NEBD. Scale bar, 10 μm.",
    "ncbi_link": "Cre: 2777477
Ndc80: 67052
Zp3: 22788"
  },
  {
    "caption": "(B) Ndc80-9D is defective for MTOC sorting. The density map of MTOCs along the spindle axis in Zp3-Cre Ndc80f/f oocytes expressing Ndc80-WT, Ndc80-9D or Ndc80-9A. The color represents the percentage of MTOC volume coded from dark (0%) to white (50% or more of the total volume).",
    "ncbi_link": "Cre: 2777477
Ndc80: 67052
Zp3: 22788"
  },
  {
    "caption": "(C) MTOCs do not accumulate at the spindle poles in Ndc80-9D-expressing oocytes. Ratio of MTOCs (green) or chromosomes (magenta) in the polar region versus those in the middle region of the spindle at 6 hours after NEBD (n=19, 19 and 22 oocytes, respectively, from at least 3 independent experiments).",
    "ncbi_link": "Ndc80: 67052"
  },
  {
    "caption": "(D) Ndc80-9A decreases central MTOCs. The number of central MTOCs (MTOCs that were positioned in the middle region of the spindle , was determined at each time point (n=19, 21 oocytes, respectively, from at least 3 independent experiments).",
    "ncbi_link": "Ndc80: 67052"
  },
  {
    "caption": "(A) Live imaging of Zp3-Cre Ndc80f/f oocytes injected with Ndc80-WT, -9D or -9A. Z-projection and 3D-reconstructed images show microtubules (EGFP-Map4, green) and chromosomes (H2B-mCherry, magenta). Scale bar, 10 μm.",
    "ncbi_link": "Cre: 2777477
Ndc80: 67052
Zp3: 22788"
  },
  {
    "caption": "(B) Ndc80-9D is defective for limiting spindle elongation. The aspect ratio (length/width) of 3D-reconstructed spindles was measured over time (n=18, 18 and 18 oocytes, respectively, from 3 independent experiments).",
    "ncbi_link": "Ndc80: 67052"
  },
  {
    "caption": "(C) Ndc80-9D causes excessive spindle elongation. Spindle lengths measured after 3D reconstruction are shown (n=18, 18 and 18 oocytes, respectively, from 3 independent experiments).",
    "ncbi_link": "Ndc80: 67052"
  },
  {
    "caption": "A. Quantitative analysis of developmental expression of Lrig1 mRNA in rat hippocampus by real-time RT-PCR. The results are shown as mean SEM of n=3 independent assays. The levels of Lrig1 mRNA were normalized using the expression of the housekeeping gene Tbp (TATA binding protein). The insert shows the expression of Lrig1 in embryonic E17.5 rat hippocampus examined by RT-PCR. Control sample without reverse transcriptase (-RT) is also shown.",
    "ncbi_link": "Tbp: 
Lrig1: 312574"
  },
  {
    "caption": "A. Representative images of mouse hippocampal neurons transfected with either GFP-expressing control or Lrig1 shRNA vector at 9 DIV and maintained for 3 additional days in vitro (9+3 DIV). Scale bar, 15 m. Boxed area represents a higher-magnification image showing the profuse proximal dendritic arborization of Lrig1-shRNA transfected neurons.B. Sholl analysis of the dendritic arbor from hippocampal neurons transfected with either control or Lrig1 shRNA-GFP vector at 9 DIV and maintained for 3 additional days in vitro (9+3 DIV). Data are shown as mean SEM of n=3 independent experiments. *p<0.05 and **p<0.01 by two-way ANOVA followed by Bonferroni multiple comparisons test.C-G. Quantification of primary (C), and secondary (D) dendrites as well as total dendritic branching (E), terminal dendritic points (F), and total dendritic length (G) of hippocampal neurons transfected with either control or Lrig1 shRNA-GFP vector. The results are shown as mean SEM of n=3 independent experiments. *p<0.05 by Students t test.",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "H. Knockdown efficiency was analyzed by real-time RT-PCR in MN1 cells transfected with control or Lrig1 shRNA vectors. Transfected cells were enriched by puromycin treatment in order to increase the population of cells expressing control or Lrig1 shRNA constructs. Data are shown as individual values of a representative assay measured in triplicates. n=2 independent experiments were performed.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "I. Representative images of MAP-2 immunostained hippocampalneurons obtained from wild-type and Lrig1-deficient mice cultured for 7 days in vitro (7 DIV). Scale bar, 15 m.J. Sholl analysis of the dendritic arbor from MAP-2 stained hippocampalneurons (7 DIV) isolated from wild type and Lrig1-deficient mice. Data are shown as mean SEM of n=3 independent experiments. *p<0.05 by two-way ANOVA followed by Bonferroni multiple comparisons test.K-M. Quantification of the number of primary dendrites (K), secondary dendrites (L) and total dendritic branching (M) from MAP-2 stained hippocampalneurons (7 DIV) isolated from wild-type and Lrig1-deficient mice. The results are shown as mean SEM of n=3 independent experiments. *p<0.05 by Students t test.",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "A. Representative images and drawings of Golgi-stainedhippocampalCA1pyramidal neurons from 4 weeks-old wild type and Lrig1-null littermate mice. Scale bar, 15 m.B. Quantification of the number of primary dendrites and branching of apical and basal dendritic arbors of hippocampalCA1pyramidal neurons from 4-5 weeks-old control (wild type/heterozygous) and Lrig1-null littermate mice. The results are shown as mean SEM of independent determinations performed in n=4 mice of each genotype. *p<0.05, **p<0.001 by Students t test. NS, not significant.C. Cummulative dendrite crossings of concentric circles of increasing radius (10 μm ring interval) centering the reference point at the cell body. These values were obtained by Sholl analysis and represent the summatory of the dendritic crossings registered within the first 60 m closest to the soma. The results are shown as mean SEM of independent determinations performed in n=4 mice of each genotype. *p<0.05 by Students t test.D. Sholl analysis of apical and basal dendritic arbors of hippocampalCA1pyramidal neurons from 4-5 weeks-old control (wild type/heterozygous) and Lrig1-null littermate mice. The results are shown as mean SEM. *p<0.05, **p<0.001 by two-way ANOVA followed by Bonferroni multiple comparisons test.Quantifications showed in B-D were performed in n=60 neurons from 4 wild type/heterozygous mice and 4 Lrig1-null littermate mice (n=4).",
    "ncbi_link": "Lrig1: 312574"
  },
  {
    "caption": "A. Schematic diagram of the social interaction device indicating the social and the empty chambers.B, C. Mice were simultaneously exposed to an empty container and a caged unfamiliar juvenile mouse (social enclosure, stranger 1). Lrig1-mutant mice exhibit social interaction defects as determined by the time spent interacting (sniffing) with the stranger enclosure (B) and the percentage of total interaction time with stranger in the three-chamber social interaction test (C). Dashed line in (C) represents chance-level performance (i.e. 50%) when mice equally explore the social enclosure and the empty container. Data represent means ± SEM of independent determinations performed in n=8-9 mice of each genotype, and the statistical significance between wt and knockout mice are *p<0.05 by Students t test.",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "A. Schematic representation of Lrig1 mutants are shown on the left. Expression levels of these mutants were analysed in transfected cell extracts by immunoblotting with anti-Flag antibodies.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "B. Representative images of rathippocampal neurons transfected at DIV8 with empty vector, full length (FL) Flag-tagged Lrig1, or Lrig1 mutant lacking the LRR domain (LRR) in combination with an enhanced green fluorescent protein (GFP) expression vector. After transfection at 9 DIV, neurons were cultured in the absence or in the presence of BDNF (30 ng/ml) for 48 h. Then, hippocampal cultures at 11 DIV were fixed and stained with anti-Flag antibodies to control Lrig1 expression. Scale bar, 15 m.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "C, D. Quantification of the effects of Flag-Lrig1 constructs on BDNF-induced primary (C) and secondary (D) dendrite formation of hippocampal neurons treated as indicated in A. The results are shown as mean SEM of 3 independent experiments. *p<0.05, **p<0.01 by one-way ANOVA followed by Tukey´s multiple comparison test. NS, not significant.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "E. Representative confocal images of dendritic shafts containing spines from hippocampal neurons transfected at 15 DIV with either control vector or Flag-Lrig1 construct together with GFP. After transfection, neurons were cultured in the absence or in the presence of BDNF (30 ng/ml) for 48 h (15+3 DIV). Scale bar, 5 m.F. Quantification of the effect of Lrig1 overexpression on neurotrophin-induced spine density. The results are shown as mean SEM of n=3 independent experiments. *p<0.05 by one-way ANOVA followed by Student-Neuman Keuls multiple comparison test.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "B. Quantitative analysis of Lrig1 mRNA expression by real-time RT-PCR. Rat hippocampal cultures (10 DIV) were treated with BDNF (50 ng/ml) during the indicated times. The levels were normalized using the expression of the housekeeping gene Tbp. The results are shown as mean SD of n=3 independent experiments. *p<0.05 vs. control group by one-way ANOVA followed by Dunnetts test.",
    "ncbi_link": "Tbp: 
Lrig1: 312574"
  },
  {
    "caption": "C, D. Coimmunoprecipitation between Flag-Lrig1 and HA-TrkB (C) or between Flag-Lrig3 and HA-TrkB (D) overexpressed in HEK293 cells. Cell extracts were analysed by immunoprecipitation with anti-Flag antibodies followed by immunoblot (IB) with antibodies against HA. Reprobing of the same blots with anti-Flag antibodies is shown below. The bottom panel shows HA expression in total lysates. Data represent n=3 independent experiments.",
    "ncbi_link": "Lrig1: 26018
Lrig3: 299830
TrkB: 25054"
  },
  {
    "caption": "E. Coimmunoprecipitation between HA-TrkB and Flag-Lrig1 or between HA-TrkB and HA-Lrig2 exogenously expressed in HEK293 cells. Cell extracts were analysed by IP with anti-pan-Trk antibodies followed by IB with antibodies against Flag or Lrig2. Reprobing of the same blots with anti-TrkB antibodies is shown below. The bottom panels show Flag and Lrig2 expression in total lysates. Data represent n=2 independent assays.",
    "ncbi_link": "Lrig1: 26018
Lrig2: 9860
TrkB: 25054"
  },
  {
    "caption": "G. Ligand-dependent activation of TrkB (p-TrkB) was evaluated by transient transfection of HA-TrkB plasmid with either a control or a Flag- Lrig1 vector into HEK cells. After 36 h cells were serum-starved and stimulated with or without BDNF (30 ng/ml) for 15 min. The level of TrkB activation (p-TrkB) was evaluated in total cell lysates by immunoblotting (IB) with a specific antibody that recognizes TrkB phosphorylated in tyrosine 705 (pY705). Reprobing of the same blot with anti-HA and anti-Flag antibodies is shown. Fold of p-TrkB change relative to total TrkB is indicated. Similar results were obtained in n=3 independent assays.",
    "ncbi_link": "Lrig1: 26018
TrkB: 25054"
  },
  {
    "caption": "H. TrkB ubiquitination was evaluated by transient transfection of HA-TrkB plasmid with either a control or a Flag-Lrig1 vector into MN1 cells. After 36 h, cells were serum-starved, pre-treated with the cell-permeable proteasome inhibitor MG-132 (20 M) and stimulated with BDNF for 15 min. Total lysates were immunoprecipitated with anti-HA antibodies followed by immunoblot (IB) with antibodies against ubiquitin. Reprobing of the same blot with anti-HA antibodies is also shown. TrkB activation (p-TrkB) was evaluated in cell lysates. Reprobing of the same blot with anti-TrkB and anti-Flag antibodies is also shown. Fold of p-TrkB (p-Y705) change relative to total TrkB is indicated. Data represent n=3 independent assays.",
    "ncbi_link": "Lrig1: 26018"
  },
  {
    "caption": "A. Immunoblot showing TrkB activation in hippocampal neurons cultured from Lrig1 heterozygous (+/-) and Lrig1 knockout (-/-) mice littermates treated in the absence or in the presence of BDNF (30 ng/ml) for 30 minutes. Reprobing of the same blot with anti- ßIII-Tubulin is shown as loading control.B. Fold of TrkB activation relative to unstimulated control group (phospho-TrkB at Tyr705) in hippocampal neurons cultured from Lrig1 (+/+; +/-) and Lrig1 (-/-) mice treated in the absence or in the presence of BDNF (30 ng/ml) for 30 minutes. Results are presented as mean SEM of n=4 independent experiments. (*p<0.05 by Students t test).",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "C. Immunoblot showing MAPK activation in hippocampal neurons cultured from Lrig1 wild-type (+/+) and Lrig1-deficient (-/-) mice littermates treated in the absence or in the presence of BDNF (30 ng/ml) for the indicated times. Reprobing of the same blot with anti- ßIII-Tubulin is shown as loading control. Fold of MAPK activation relative to tubulin is indicated.D. Fold of MAPK activation (P-MAPK) relative to untreated control group in hippocampal neurons cultured from Lrig1 (+/+; +/-) and Lrig1 (-/-) mice treated in the absence or in the presence of BDNF (30 ng/ml) for 30 minutes. Results are presented as mean SEM of n=4 independent experiments. (*p<0.05 by Students t test).",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "E. Representative images of mousehippocampal neurons transfected at 4 DIV with either GFP-expressing control vector or Lrig1shRNA-GFP plasmid. After transfection, neurons were cultured in the absence or in the presence of BDNF (25 ng/ml) for 48 h (7 DIV). Arrows indicate branching points along the principal dendrite. Scale bar, 10 m.",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "J. Lrig1+/+ and Lrig1-/- hippocampal lysates from postnatal day 11 (P11) mice were immunoblotted against phospho-TrkB (p-TrkB) at Tyr705 and total TrkB. Quantification (mean SD) of the p-TrkB/TrkB ratio between Lrig1+/+ (n=4) and Lrig1-/- (n=3) hippocampi is also shown.",
    "ncbi_link": "Lrig1: 16206"
  },
  {
    "caption": "Volcano plot of RNAseq gene expression in splenic WT and miR-132-/- CD4+ T cells from d28 L. donovani infected mice. Fold change determined as log2 mean FPKM (miR-132-/-/WT) from 4 WT and 5 miR-132-/- mice. Transcripts significantly different between WT and miR-132-/- (p<0.05) are shown in red. Dotted box indicates transcripts significantly up-regulated in miR-132-/- CD4+ T cells by more than 50%.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "STRING network analysis of significantly up-regulated transcripts in CD4+ T cells from spleen of d28 L. donovani infected miR-132-/- mice compared to WT cells. Cluster of ribosomal proteins shown in green circle, with coding RP transcripts (black) and pseudogenes (red) indicated. Secondary clusters are shown in grey.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Volcano plot of all RP genes in splenic WT and miR-132-/- CD4+ T cells from d28 L. donovani infected mice. RPL genes are shown as circles, RPS genes as triangles, and pseudogenes as squares. Red symbols indicate significant difference between WT and miR-132-/- cells (p<0.05) whereas black non-significant.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Expression of RP transcripts determined by qPCR from L. donovani infected d28 WT (blue) and miR-132-/- mice (red). N=9 for each WT and miR-132-/- from 2 independent infection experiments. Box extends from 25-75th percentile, whiskers are minimum and maximum values, and horizontal lines indicate median. Significance determined by unpaired t-test. Data information: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "A. Volcano plot (Log2(Fold Change) vs -Log(P value)) of RNA gene expression in purified naïve CD62L+ CD44- WT and miR-132-/- CD4+ T cells. Fold change determined as log2 mean FPKM (miR-132-/-/WT) from 4 WT and 4 miR-132-/- mice. Transcripts significantly different between WT and miR-132-/- cells (p<0.05) shown in red.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "B. Volcano plot of RNA gene expression in purified naïve CD62L+ CD44- WT and miR-132-/- CD4+ T cells following 18hr in vitro stimulation with anti-CD3/anti-CD28 under Th1 conditions. Fold change determined as log2 mean FPKM (miR-132-/-/WT) from 4 WT and 4 miR-132-/- mice. Transcripts significantly different between WT and miR-132-/- cells (p<0.05) shown in red.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "C. Volcano plot of transcripts containing a conserved miR-212/132-3p target site in naïve CD4+ T cells from WT or miR-132-/- mice.",
    "ncbi_link": "132-3p: 387150
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "D. Volcano plot of transcripts containing a conserved miR-212/132-3p target site in in vitro polarised (Th1 condtions, 18h post stimulation) CD4+ T cells from WT or miR-132-/- mice.",
    "ncbi_link": "132-3p: 387150
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "E. Volcano plot of transcripts containing a conserved miR-212/132-3p target site in spleen CD4+ T cells from d28 L. donovani infected WT or miR-132-/- mice.",
    "ncbi_link": "132-3p: 387150
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "F. BTAF1 transcript levels determined by qRTPCR in WT (blue) or miR-132-/- (red) in naïve (d0) and Th1 polarised for 18h (d1) CD4+ T cells, and CD4+ T cells from d28 L. donovani infected WT or miR-132-/- mice. N=8-9 for each WT and miR-132-/ Data information: Significance in (F) determined by unpaired t-test. * p<0.05, ** p<0.01.",
    "ncbi_link": "BTAF1: 107182
miR-132: 387150"
  },
  {
    "caption": "G. Expression of BTAF1 protein in d0 naïve and d1 (18hr) Th1-polarised WT and miR-132-/- CD4+ T cells, as determined by Western blot. Each lane from individual mouse, and representative of two independent experiments.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "H. Relative luciferase activity in HeLa transfected with plasmid containing WT BTAF1 3'UTR (white) or BTAF1 3'UTR on which the miR-132 binding site is mutated (grey) downstream of renilla luciferase, in the presence of miR-132-3p or miR-212-3p mimics. Error bars indicate SEM from eight replicate treatments. Data information: Significance in (H) determined by unpaired t-test. * p<0.05, ** p<0.01.",
    "ncbi_link": "BTAF1: 107182
miR-132: 387150
miR-132-3p: 387150
miR-212-3p: 387208"
  },
  {
    "caption": "A. mRNA levels of indicated RP transcripts determined by qRTPCR in MEFs transfected with Non-targeting control (NTC) mimics (white) or miR-132-3p mimics (grey). * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "miR-132-3p: 387150"
  },
  {
    "caption": "B. p300 and BTAF1 protein levels in MEF transfected with NTC mimics or miR-132-3p mimics determined by Western blot. GAPDH was used as a loading control. Right panel indicates mean + SEM of 4 experiments. * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "miR-132-3p: 387150"
  },
  {
    "caption": "C. mRNA levels of indicated RP transcripts determined by qRTPCR in MEFs transfected with NTC siRNA (white) or p300 siRNA (grey). * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "p300: 328572"
  },
  {
    "caption": "D. mRNA levels of indicated RP transcripts determined by qRTPCR in MEFs transfected with NTC siRNA (white) or BTAF1 siRNA (grey). Data information: Statistical significance is determined by unpaired t-test",
    "ncbi_link": "BTAF1: 107182"
  },
  {
    "caption": "E. mRNA levels of indicated RP transcripts determined by qRTPCR in MEFs transfected with NTC or miR-132-3p mimics and NTC siRNA or p300 or BTAF1 siRNAs for 48h. Levels are normalised to cells transfected with NTC siRNA and NTC mimic. Data information: Statistical significance is determined by unpaired t-test * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "BTAF1: 107182
p300: 328572
miR-132-3p: 387150"
  },
  {
    "caption": "F. Puromycin incorporation (following 10-minute pulse and 50-minute chase) determined by western blot in MEFs transfected with NTC or miR-132-3p or miR-212-3p mimics. Data information: Statistical significance is determined by unpaired t-test",
    "ncbi_link": "miR-132-3p: 387150
miR-212-3p: 387208"
  },
  {
    "caption": "A. Percentage of IFNγ+ live TCRβ+ CD4+ cells from L. donovani infected WT (blue) or miR-132-/- (red) mice, determined by intracellular cytokine staining. Data representative of 3 independent experiments with 3-5 mice per group. Data information: statistical significance was determined by unpaired t-test. * p<0.05, ** p<0.01, *** p<0.001. NS: not significant.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "B. Percentage of IFNγ+/IL-10+ live TCRβ+ CD4+ cells from L. donovani infected WT (blue) or miR-132-/- (red) mice, determined by intracellular cytokine staining. Data representative of 3 independent experiments with 3-5 mice per group. Data information: statistical significance was determined by unpaired t-test. * p<0.05, ** p<0.01, *** p<0.001. NS: not significant.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "C. IL-10 mRNA levels, determined by RNA-sequencing, in TCRβ+ CD4+ cells purified from spleens of L. donovani infected WT (blue) or miR-132-/- (red) mice (n=5 per group).",
    "ncbi_link": "IL-10: 16153
miR-132: 387150"
  },
  {
    "caption": "D. Percentage of IFNγ+ WT (blue) or miR-132-/- (red) in vitro polarised Th1 cells (6 days) in the presence or absence of phenylephrine (PE), determined by intracellular cytokine staining. E. Percentage of IL10+ WT (blue) or miR-132-/- (red) in vitro polarised Th1 cells (6 days) in the presence or absence of phenylephrine (PE), determined by intracellular cytokine staining. F. Total cell counts following in vitro Th1 polarisation (6 days) in the presence or absence of phenylephrine (PE). For (D-E), cells were purified from 3 mice per group and 6 replicates performed. Data information: statistical significance was determined with 1-way ANOVA followed by Bonferroni's multiple comparison test. * p<0.05, ** p<0.01, *** p<0.001. NS: not significant.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Liver LDU (Leishman Donovan units) at day 28 in infected WT mice treated with anti-IL-10R antibody or isotype control antibody (left panel, n=5 mice per group), or at day 21 and day 28 from WT (blue), IL-10+/- (open green circles) and IL-10-/- (filled green circles) mice (right panel n= 3-6 mice per group) Data information: Significance determined by unpaired t-test * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "IL-10: 16153"
  },
  {
    "caption": "Day 28 splenic parasite burdens expressed as LDU with each data point representing an individual mouse in WT (blue) and miR-132-/- (miR-132-/-; red) mice. Data from 4 independent infection experiments.   Mean WT and miR-132-/- spleen parasite burdens from the 4 independent experiments shown in (B). Lines link individual experiments.   Splenic parasite burdens relative to WT group (WT mean = 1) for each of the 4 experiments shown in (B), with each data point representing individual mouse.   Data information: Significance determined by unpaired t-test, and in (C) by paired t-test of mean values. * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Spleen size expressed as % body weight for d0 (naïve) or day 28 L. donovani infected WT (blue) and miR-132-/- (miR-132-/-; red) mice.   Liver size expressed as % body weight for d0 (naïve) or day 28 L. donovani infected WT (blue) and miR-132-/- (red) mice.   Data information: Significance determined by unpaired t-test * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "RNAi was induced with an empty vector as a negative control (panel I), whereas a smg-2 clone (panel II) was used as a positive control. Panels i and ii show brightfield images of the PTCxi strain treated with the negative and positive controls, respectively. Depletion of five genes (panels III to VII) resulted in increased GFP expression. Panels iii to vii show brightfield images of the phenotypes of the affected worms. The scale bars correspond to 100 μm.",
    "ncbi_link": "smg-2: 171696"
  },
  {
    "caption": "Depletion of the novel NMD genes in C. elegans leads to upregulation of the PTCx NMD reporter mRNA, which was monitored by quantitative RT-PCR relative to the expression of ama-1 reference gene. The values shown are the average fold-change (mean ± SEM) from at least three independent experiments relative to empty vector-depleted worms. Statistical analysis was performed using the Mann-Whitney U-test for non-parametric distributions. *P < 0.05.",
    "ncbi_link": "ama-1: "
  },
  {
    "caption": "A-C Embryos expressing a GFP-NMD sensor (green) under the control of nompA regulatory sequences show signal in support cells linked to the embryonic peripheral nervous system (PNS) [labeled by 22C10 signal (magenta)]. DAPI signal is shown in blue. Expression of UAS-RNAi constructs against Upf1 (B) or nompA (C) genes using a nompA-Gal4 driver leads to upregulation of the GFP-NMD sensor when compared to wild-type (no RNAi) (A), revealing a reduction in NMD activity in the knockdown conditions. Scale bars represent 100 μm.D-F Higher magnification (40×) of the areas marked by a rectangle in (A-C) further illustrates the upregulation of the GFP-NMD sensor in Upf1- (E) and NompA-depleted cells (F). Optical fields include embryonic abdominal segments A4-A5. Scale bars represent 10 μm.",
    "ncbi_link": "Gal4: 
UAS: 
nompA: 45587
NompA: 45587
Upf1: 32153"
  },
  {
    "caption": "G Quantification of GFP signal in cells marked by an arrow in panels (D-F) shows a significant upregulation of NMD sensor expression upon downregulation of Upf1 (dark gray) and NompA (black) compared to wild-type (no RNAi) (light gray). Results represent the average of five biological replicates (mean ± SEM). Pair-wise comparisons were performed using a one-tailed t-test (non-parametric) between treatments and wild-type. ***P < 0.001.",
    "ncbi_link": "NompA: 45587
Upf1: 32153"
  },
  {
    "caption": "A, B HeLa cells stably expressing a wild-type β-globin reporter (A) or a β-globin NS39 NMD reporter (B) were mock-depleted or depleted of UPF2, GNL2, SEC13, RAB27A, RAB27B or both RAB27A and RAB27B. The level of the β-globin mRNA was monitored by quantitative RT-PCR relative to two reference genes (POLR2J and ACTB). The values shown are the average fold-change (mean ± SEM) from four independent experiments relative to mock-depleted cells (control). Statistical analysis was performed using the Mann-Whitney U-test for non-parametric distributions. *P < 0.05. The level of depletion of NMD factors is shown in Supplementary Fig S3C.",
    "ncbi_link": "ACTB: 
POLR2J: 
GNL2: 29889
β-globin: 3043
RAB27A: 5873
RAB27B: 5874
SEC13: 6396
UPF2: 26019"
  },
  {
    "caption": "C, D Analysis of the half-life of β-globin reporters. Samples were collected at the indicated time points, and the mRNA levels of the HBB reporters were monitored by qRT-PCR and normalized to POLR2J and ACTB reference genes. The values shown are the average fold-change (mean ± SEM) from three independent experiments relative to the first time point.",
    "ncbi_link": "ACTB: 
POLR2J: 
HBB: 3043
β-globin: 3043"
  },
  {
    "caption": "E Depletion of GNL2 and SEC13 leads to a significant upregulation in the mRNA levels of endogenous NMD substrates. Samples were analyzed as described in (A, B) *P < 0.05; ***P < 0.01, ***P < 0.001.",
    "ncbi_link": "GNL2: 29889
SEC13: 6396"
  },
  {
    "caption": "F GNL2 and SEC13 contribute to the negative NMD feedback loop, regulating the levels of transcripts encoding NMD factors. RT-qPCR analysis of total cellular RNA from HeLa cells depleted of GNL2 (in green) and SEC13 (in purple) is shown. The graph shows distribution of relative fold-change from eight independent experiments relative to mock-depleted cells (control). Statistical analysis was performed using Student's t-test. *P < 0.05.",
    "ncbi_link": "GNL2: 29889
SEC13: 6396"
  },
  {
    "caption": "Northern blot of candidate tRNAs and tsRNAs tsGlnCTG, tsGlyGCC, tsGluTTC, tsValCAC and tsLysTTT. The black arrows represent the tRNAs and the red arrows mark the tsRNAs.",
    "ncbi_link": "tsRNAs: "
  },
  {
    "caption": "Northern Blot of 5'-tsRNAs; tsGlyGCC, tsGlnCTG, tsGluTTC, tsLysTTT, tsValCAC at various timepoints of RA-induced mESCs differentiation showing dynamic expression of these 5'-tsRNAs. Relative quantification of the tsRNA bands from northern hybridization tested across two biological replicates. The solid lines represent the expression of tsRNAs and the dashed lines represent tRNAs.",
    "ncbi_link": "tsRNA: 
tsRNAs: "
  },
  {
    "caption": "Effect of ASO-mediated inhibition of 5'-tsRNAs on alkaline phosphatase activity in RA-treated mESCs. (n = 3), Error bars represent SEM, significance was calculated using unpaired t-test.",
    "ncbi_link": "tsRNAs: "
  },
  {
    "caption": "Relative expression of stemness markers in RA-induced differentiation mESCs blocked for 5'-tsRNA function with ASOs. (n = 2) Error bars represent SEM, significance was calculated using unpaired t-test.",
    "ncbi_link": "tsRNA: "
  },
  {
    "caption": "QPCR validation of transcripts involved in the stem cell signalling pathway that are upregulated upon 5'-tsRNA knockdowns using ASOs. (n =2) Error bars represent SEM, significance was calculated using unpaired t-test.",
    "ncbi_link": "tsRNA: "
  },
  {
    "caption": "Quantification of the Igf2bp1 bound c-Myc mRNA between LIF- versus RA-treated mESCs (n = 2; see Fig. EV5F for duplicate data).",
    "ncbi_link": "c-Myc: 17869"
  },
  {
    "caption": "Association of c-Myc transcript in different translating pools in RA treated mESCs as compared to LIF condition. (n = 2), Error bars represent SD, significance was calculated by one-tailed unpaired t-test.",
    "ncbi_link": "c-Myc: 17869"
  },
  {
    "caption": "Relative enrichment of c-Myc mRNA in translating (80S and Polysome) and non-translating (mRNPs) pools (fractionated from polysome profiling) between ASO-treated and Mock-treated RA-induced differentiating mESCs. (n =2) Error bars represent SD, significance was calculated using one-tailed unpaired t-test.",
    "ncbi_link": "c-Myc: 17869"
  },
  {
    "caption": "Relative levels of c-Myc mRNA in ASO-treated and Mock-treated RA-induced differentiating mESCs compared to LIF treated mESCs. (n = 3) Error bars represent SD, significance was calculated using one-tailed unpaired t-test.",
    "ncbi_link": "c-Myc: 17869"
  },
  {
    "caption": "Epistatic analysis of 5'-tsRNAs and IGF2BP1 in regulating Myc transcriptional reporter activity. (n = 3), Error bars represent SD, significance was calculated using unpaired t-test.",
    "ncbi_link": "IGF2BP1: "
  },
  {
    "caption": "C (i) Low magnification overview of the  spinal cord of a cilium  reporter line, Tg(actb2:arl13b-GFP) from a single confocal  slice. (ii) High resolution image sequence of boxed section in (i). One GFP-labelled cilium  moves from apical  surface  towards the basal  surface  of the spinal cord  (n = 13 cilia  from two experiments). Images are maximum projections from confocal  z-stacks. Data information: All scale bars = 10 µm.",
    "ncbi_link": "GFP: 
actb2: 57935
arl13b: 286784"
  },
  {
    "caption": "D (i) Low magnification overview of the spinal cord of a Tg(actb2:arl13b-GFP) embryo labelled  with centrin-RFP  from a single confocal  slice. (ii) Image sequence of boxed section in (i). A cilium and centrosome  move together from apical  surface  towards the  basal surface of the spinal cord (n = 2 cells from one experiment). Insets show high magnification of cilium-centrosome  pair. Images are maximum projections from confocal  z-stacks. Data information: All scale bars = 10 µm.",
    "ncbi_link": "GFP: 
actb2: 57935
arl13b: 286784"
  },
  {
    "caption": "F Distance between centrosome  and cilium  in Tg(actb2:arl13b-GFP) embryos  fixed and processed for immunohistochemistry   against GFP  to label the cilium  and γ-tubulin to label the centrosome. No difference was found in the distance between the two organelles when close to the  apical surface or away from the midline   (n = 50 cells per position from two experiments; P = 0.8279; midline  mean = 0.4956, s.d = 0.1125; away from midline  mean = 0.5004, s.d = 0.1077; Student's unpaired t-test). Bars show mean and standard deviation.",
    "ncbi_link": "GFP: 
actb2: 57935
arl13b: 286784"
  },
  {
    "caption": "A Transverse section from a confocal  z-stack showing the whole neural tube of a utr-mCherry embryo, showing localisation  to the  basal surface. B Transverse sections from a confocal  z-stack of a  non-apical progenitor labelled with a membrane  marker in a utr-mCherry embryo  to identify the basal surface of the spinal cord. Image sequence from confocal time-lapse shows the non-apical progenitor (-44m) undergoing mitosis to produce two neurons  (-22m), of which one is not in contact with the basal surface. Both neurons  extend nascent axons (0m). Data information: All scale bars = 5 µm.",
    "ncbi_link": "mCherry: 
utr: "
  },
  {
    "caption": "C Transverse sections from a confocal  z-stack of a neuron  at the time  of nascent axon initiation labelled with a membrane  marker in a utr-mCherry embryo  to identify the basal surface  of the spinal cord. Three different sections show the middle of the soma, the axon  initiation site, and the  axon tip. Green and magenta peaks in graphs show relative positions of cell membrane and basal surface, respectively. D Transverse sections from confocal  z-stacks of a neuron  at the time  of nascent axon initiation labelled with a membrane  marker in a utr-mCherry embryo  injected with  lamMO. Three different sections show the middle of the soma, the axon  initiation site, and the axon tip. Green and magenta peaks in graphs show relative positions of cell membrane and basal surface, respectively. E Graphs showing distance (µm) between the basal edge of the soma, the axon  initiation site or the axon tip and the  basal surface of the spinal cord. Measurements were performed by measuring between basal-most green and magenta peaks in graphs of relative grey values (C, D). Bars show mean and standard deviation. WT: n = 5 cells from one experiment; lamMO: n = 11 cells from two experiments. Soma: WT mean = 2.007 µm, s.d. = 1.055;  lamMO  mean = 1.871 µm, s.d. = 1.830. Student's two-tailed test, P = 0.880. Axon  initiation site: WT mean = 1.366 µm, s.d. = 3.13; lamMO mean = 2.353 µm, s.d. = 2.125. Student's two-tailed test, P = 0.468. Axon tip: WT mean = 0.637 µm, s.d. = 1.078; lamMO mean = 2.903 µm, s.d. = 2.0433. Student's two-tailed test, P = 0.037. Data information: All scale bars = 5 µm. * P < 0.05.",
    "ncbi_link": "mCherry: 
utr: 
lam: 286832"
  },
  {
    "caption": "F Image sequence from confocal time lapse shows a neuron  in a Sly-/- embryo  labelled with membrane  and centrosome  markers before (-40m), during (0) and after axon  initiation (20m). Images are transverse reconstructions from confocal  z-stacks.",
    "ncbi_link": "Sly: 286832"
  },
  {
    "caption": "G Plots showing axon  position on the soma  relative to the cell centroid  at 0,0 for dorsal and transverse view in Sly-/- embryos  (n = 18 cells from three experiments). Axon  position is not random (dorsal view P < 0.001, mean = 98.8o; transverse view P < 0.001, mean = 161.1o; Moore's modification of Rayleigh's test). H Plots showing merge of WT and Sly-/- axon  positions on the cell body relative to  cell centroid  at 0,0 for dorsal and transverse views. Axon  positions in WT and Sly-/- are not significantly different in dorsal view (0.2 < P < 0.5) but are in transverse view (P < 0.001; Batschelet's alternative to Hotelling test). WT: n = 86 cells from eight experiments; Sly-/-: n = 18 cells from three experiments.",
    "ncbi_link": "Sly: 286832"
  },
  {
    "caption": "I Graph showing distance between centrosome  and base of axon  at time of axon  initiation in WT and Sly-/- embryos. Bars show mean and standard deviation. WT: n = 26 cells from three experiments, mean = 10.13 µm, s.d. = 3.35. Sly-/-: n = 15 cells from two experiments, mean = 12.41 µm, s.d. = 3.281. One-way ANOVA, P = 0.123.",
    "ncbi_link": "Sly: 286832"
  },
  {
    "caption": "J Plots showing centrosome  position relative to the  cell centroid at 0,0 for dorsal and transverse view in Sly-/- embryos  (n = 15 cells from two experiments). Centrosome  position is not random (dorsal view P < 0.001, mean = -129.0o; transverse view 0.001 < P < 0.005, mean = -57.0o; Moore's modification of Rayleigh's test). K Plots showing merge of WT and Sly-/- centrosome  positions on the cell body  relative to cell centroid  at 0,0 for dorsal and transverse views. Centrosome  positions are not significantly different between WT and Sly-/- (dorsal view 0.2 < P < 0.2, transverse view 0.1 < P < 0.2; Batschelet's alternative to Hotelling test). WT: n = 26 cells from three experiments; Sly-/-: n = 15 cells from two experiments.",
    "ncbi_link": "Sly: 286832"
  },
  {
    "caption": "L Plots showing the positions of the centrosome  and base of the axon  in Sly-/- embryos  at the time of axon  initiation relative to the cell centroid at 0,0 for dorsal and transverse view (n = 15 cells from two experiments). Left-hand plots: centrosome  position is not random (dorsal view P < 0.001, mean = -129.0o; transverse view P < 0.001, mean = -57.0) and axon  position is not random (dorsal view P < 0.001, mean = 95.1o; transverse view P < 0.001, mean = 168.8o, Moore's modification of Rayleigh's test). Centrosome  and axon  positions are significantly different (dorsal view 0.001 > P; transverse view 0.001 > P; Moore's test for paired data). Right-hand plots: vectors connecting centrosome  and  nascent axon from the same cell are not random (dorsal view P < 0.001, mean = 66.1o; transverse view P < 0.001, mean = 150.9o).",
    "ncbi_link": "Sly: 286832"
  },
  {
    "caption": " D) RT-qPCR analysis of expression of CaSR in human spinal tissue. n=3, Student's t-test. ",
    "ncbi_link": "CaSR: 846"
  },
  {
    "caption": "(D) RT-qPCR analysis of expression of CaSR in spinal ligament tissuse. n=3, Student's t-test.",
    "ncbi_link": "CaSR: 12374"
  },
  {
    "caption": " (D) RT-qPCR analysis of expression of CaSR in hind paw tissue. n=3, Student's t-test. ",
    "ncbi_link": "CaSR: 12374"
  },
  {
    "caption": " (A) RT-qPCR and Western Blot analyses of CaSR expressions in MC3T3-E1 cells treated with IL-1β. n=3, one‐way ANOVA, Bonferroni post hoc. ",
    "ncbi_link": "CaSR: 12374
IL-1β: 16176"
  },
  {
    "caption": " (B) RT-qPCR and Western Blot analyss of CaSR expressions in MC3T3-E1 cells treated with TNFα. n=3, one‐way ANOVA, Bonferroni post hoc. ",
    "ncbi_link": "CaSR: 12374
TNFα: 21926"
  },
  {
    "caption": " (C) RT-qPCR and Western Blot analyses of CaSR expressions in MC3T3-E1 cells treated with IL-17A. n=3, one‐way ANOVA, Bonferroni post hoc. ",
    "ncbi_link": "CaSR: 12374
IL-17A: 16171"
  },
  {
    "caption": " (D) RT-qPCR and Western Blot analyses of CaSR expressions in MC3T3-E1 cells treated with IL-22. n=3, one‐way ANOVA, Bonferroni post hoc. ",
    "ncbi_link": "CaSR: 12374
IL-22: 50929"
  },
  {
    "caption": " (E) RT-qPCR and Western Blot analyses of CaSR expressions in MC3T3-E1 cells treated with IL-23. n=3, one‐way ANOVA, Bonferroni post hoc. ",
    "ncbi_link": "CaSR: 12374
IL-23: 83430"
  },
  {
    "caption": "(A-D) Images of a representative wild-type adult eye (A) or adult eyes containing mtm mutant clones (B and C). Quantification of relative eye sizes (n=10) (D).",
    "ncbi_link": "mtm: 33845"
  },
  {
    "caption": "(F-G) A pupal eye disc containing mtm mutant clones (marked by the absence of GFP) was stained for Dlg. Note the increased interommatidial cells in the mtm mutant clone. Quantification of numbers of interommatidial cells per ommatidium (n=10) (G).",
    "ncbi_link": "mtm: 33845"
  },
  {
    "caption": "(K) RNAi of Mtm reduces Yki phosphorylation. Kc167 cells were incubated with dsRNA of gfp or mtm for three days before western blot analysis. Total cell lysates were probed with anti-phospho-Yki (p-Yki) antibody. Note that RNAi of mtm decreased Yki phosphorylation.",
    "ncbi_link": "gfp: 
mtm: 33845
Mtm: 33845"
  },
  {
    "caption": "PI(3)P expression levels detected by a 2xFYVE-GFP reporter in a third instar larval wing disc (A) and eye disc (B) containing mtm mutant clones (marked by the absence of RFP). Ten different mtm clones and surrounding regions in three biological replicates were used for the analysis. Note the strong increases of PI(3)P levels in the mtm mutant clones.",
    "ncbi_link": "mtm: 33845"
  },
  {
    "caption": "Quantification of the mean FYVE-GFP fluorescence intensity of mtm mutant clones and surrounding wild-type (WT) cells are shown (C). Ten different mtm clones and surrounding regions in three biological replicates were used for the analysis. Note the strong increases of PI(3)P levels in the mtm mutant clones.",
    "ncbi_link": "mtm: 33845"
  },
  {
    "caption": "(B, C) Percentage of GAPDH or 5.8 rRNA levels quantified by  qPCR in reactions containing increasing doses of (PR)20 (n=3).Data represent mean values ± SEM. Data information: **, p<0.01; ***, p<0.001; ****, p<0.0001; t-test.",
    "ncbi_link": "GAPDH: 2597
5.8 rRNA: 110255166///110255170///106632261///106632262///106632263"
  },
  {
    "caption": "(A) Cells were grown to mid‐exponential phase and then incubated in the presence of 3.5% galactose to induce expression of GFP-Atg8. Aminopeptidase I (API) maturation was tested in cells incubated in control or starvation medium by western blot analysis using anti‐Atg8 (right bottom panel), anti‐GFP (left bottom panel) or anti‐API antibodies (upper panel).",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(A) Atg8WT-HA, Atg8F77A-HA, Atg8F79A-HA or Atg8F77/79A-HA was transformed into Δatg8 cells. Cell extracts were prepared and subjected to 13.5% SDS-polyacrylamide gel electrophoresis (SDS-PAGE) containing 6 M urea, followed by immunoblot analysis with anti-Atg8 antibodies.",
    "ncbi_link": "Atg8: 852200
atg8: 852200"
  },
  {
    "caption": "(C) Pull‐down assay of Atg8 mutants with Atg4. His-Atg4 was attached to cobalt beads (Talon metal‐affinity resin), washed and incubated with total cell extracts of Atg8 mutants. Elution was subjected to SDS-PAGE followed by western blot analysis using anti‐Atg8 and anti‐Atg4 antibodies.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(D) Localization of green fluorescent protein (GFP)-Atg8wt and GFP-Atg877/79 cells carrying Atg4 plasmid under normal (control) and starvation conditions. Arrows point to the pre‐autophagosomal structure, and arrowheads point to GFP within the vacuoles.",
    "ncbi_link": "Atg4: 855498
Atg8: 852200"
  },
  {
    "caption": "(A) Δatg8 cells transformed with GFP-Atg8WT, GFP-Atg8L50A or GFP-Atg8Y49A constructs were grown to mid‐exponential phase and then incubated in the presence of 3.5% galactose to induce expression of GFP-Atg8. API maturation was tested using anti‐Atg8 (right bottom panel), anti‐GFP (left bottom panel) or anti‐API antibodies.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(C) Atg8WT-HA, Atg8L50A-HA or Atg8Y49A-HA was transformed into Δatg8 and Δatg8Δatg4 double knockout strains and cell extracts were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblot analysis using anti‐HA antibodies (lower panel; asterisk represents nonspecific band).",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(D) Atg8WT, Atg8L50A or Atg8Y49A was transformed into Δatg8 and Δatg8Δatg4 double knockout strains and grown under control or starvation conditions for 4 h. Cell extracts were subjected to 13.5% SDS-PAGE containing 6 M urea, followed by immunoblot analysis using anti‐Atg8‐N15 antibodies. GFP, green fluorescent protein; WT, wild type.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "A Scatterplot representing differences in ssGSEA immune signatures in TERThigh versus TERTlow tumours (n = 4,632 tumours in each group) across TCGA. -log10(padj) for enrichment of ssGSEA immune signatures in TERThigh versus TERTlow tumours is shown on the y-axis. Signatures more highly represented in TERThigh tumours are shown on the right, while those in TERTlow tumours are shown on the left.",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "D-F RT-qPCR analysis of interferon-related genes (D), western blot analysis of TERT, TBK1, pTBK1, IRF3, pIRF3, and GAPDH levels (E), and ELISA of IFNβ and CXCL10 in culture supernatant (F) in U2OS and HeLa cells ectopically expressing TERT-WT or TERT-K626A.",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "D RT-qPCR analysis of TA-ERVs in U2OS and HeLa cells ectopically expressing TERT-WT or TERT-K626A. E RT-qPCR analysis of TA-ERVs in HeLa and HCT116 cells with TERT knockdown. F",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "F-H RT-qPCR analysis of interferon-related genes and TA-ERVs (F), western blot analysis of TERT, TBK1, pTBK1, IRF3, pIRF3, and GAPDH levels (G), and ELISA of IFNβ and CXCL10 in culture supernatant (H) in U2OS cells ectopically expressing TERT-WT or TERT-K626A using Dox-inducible system. GFP was used as negative control. Relative levels of pTBK1 and pIRF3 were quantified with ImageJ software and normalized to GAPDH, as indicated at the bottom of the blot (G).",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "D MeDIP-qPCR analysis of TA-ERVs sites in HeLa cells ectopically expressing TERT-WT or TERT-K626A. Primer sets recognizing exon 8 of the human ZC3H13 gene and a gene desert on chromosome 12 were used for positive and negative controls, respectively.",
    "ncbi_link": "TERT: 7015
ZC3H13: 23091"
  },
  {
    "caption": "E ChIP-qPCR for TERT and Sp1 targets on TA-ERVs in U2OS cells with TERT ectopic expression and in HeLa cells. GAPDH promoter was used as a negative control, and VEGF promoter was used as a positive control.",
    "ncbi_link": "GAPDH: 
TERT: 7015
VEGF: 7423"
  },
  {
    "caption": "A Expression of murine ERVs in blood of WT and G1 Tert-/- mice. n = 5 mice per group. B Expression of MMERGLN_LTR and MMERGLN-int in livers of WT and G1 Tert-/- mice treated with ENU or saline (control). n = 3 mice per group. C",
    "ncbi_link": "Tert: 21752"
  },
  {
    "caption": "D Heat map showing log2 fold change differences of interferon-related genes expression between ENU treatment and control (saline) in WT and G1 Tert-/- mice by RNA-seq. n = 3 mice per group. E Heat map showing log2 fold change differences of cytokine/chemokine between ENU treatment and control (saline) in WT and G1 Tert-/- mice by cytokine/chemokine array. n = 5 mice per group. F",
    "ncbi_link": "Tert: 21752"
  },
  {
    "caption": "B TCGA fragments per kilobase million (FPKM) values of TERT, CXCL10, ISG15, and OASL in tumours grouped in TERThigh (n = 500) and TERTlow groups (n = 500). Data represent mean ± SD. P-values were analysed using unpaired two-tailed Student's t-tests.",
    "ncbi_link": "CXCL10: 3627
ISG15: 9636
OASL: 8638
TERT: 7015"
  },
  {
    "caption": "C TCGA FPKM values of interferon-related genes in tumours grouped in TERThigh (n = 500) and TERTlow (n = 500) groups. Heat map showing mean FPKM values of each gene.",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "Expression of TERT (D) in TERThigh and TERTlow cancer types (6 types in each). ACC (adrenocortical carcinoma), n = 79. KICH (kidney chromophobe), n = 66. KIRP (kidney renal papillary cell carcinoma), n = 291. LGG (brain lower grade glioma), n = 532. PRAD, n = 502. THCA, n = 513. BLCA (bladder urothelial carcinoma), n = 414. CESC (cervical squamous cell carcinoma and endocervical adenocarcinoma), n = 306. DLBC (lymphoid neoplasm diffuse large B-cell lymphoma), n = 48. LUSC (lung squamous cell carcinoma), n = 502. OV (ovarian serous cystadenocarcinoma), n = 430. All boxplots include the median line, box indicates the interquartile range (IQR) and whiskers denote the 1.5 × IQR. P-values were analysed using two-tailed Mann-Whitney U test.",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "Expression of DDX58, IFIH1, CXCL10, IFI44, ISG15, and OASL (E) in TERThigh and TERTlow cancer types (6 types in each). ACC (adrenocortical carcinoma), n = 79. KICH (kidney chromophobe), n = 66. KIRP (kidney renal papillary cell carcinoma), n = 291. LGG (brain lower grade glioma), n = 532. PRAD, n = 502. THCA, n = 513. BLCA (bladder urothelial carcinoma), n = 414. CESC (cervical squamous cell carcinoma and endocervical adenocarcinoma), n = 306. DLBC (lymphoid neoplasm diffuse large B-cell lymphoma), n = 48. LUSC (lung squamous cell carcinoma), n = 502. OV (ovarian serous cystadenocarcinoma), n = 430. All boxplots include the median line, box indicates the interquartile range (IQR) and whiskers denote the 1.5 × IQR. P-values were analysed using two-tailed Mann-Whitney U test.",
    "ncbi_link": "CXCL10: 3627
DDX58: 23586
IFI44: 10561
IFIH1: 64135
ISG15: 9636
OASL: 8638
TERT: 7015"
  },
  {
    "caption": "G Representative sections of immunohistochemical staining of CD4 and FOXP3 in TERT-ERVshigh and TERT-ERVslow colon tumours. Red arrowheads indicate FOXP3+ cells. Scale bar = 100 μm.",
    "ncbi_link": "TERT: 7015"
  },
  {
    "caption": "(A) Design of a functional dynamin mutant to probe PHD stalk interactions. Minimal structure of the PHD and the PHD-Stalk interface showing the location of important residues discussed in this study. The unresolved loop L1NS in the stalk hosts the IAEDANS label and is sensitive to the two tryptophans (W525 and W542) in the PHD. The distance between two introduced cysteines (S357C and native C602) used to construct a double cysteine Dyn1 is also shown.",
    "ncbi_link": "dynamin: "
  },
  {
    "caption": "(B) Histogram shows basal and assembly-stimulated GTPase activities of non-crosslinked Dyn1CC vs crosslinked Dyn1Closed and Dyn1WT. Inset shows crosslinking of the PHD and stalk domains in Dyn1Y354C/S607C (Dyn1CC) with the bifunctional crosslinker, MTS-2-MTS, to yield Dyn1Closed, which migrates more slowly on SDS-PAGE, as well as liposome binding of Dyn1CC compared to Dyn1Closed (Bound, B; Unbound, UB).",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(C) Ability of Dyn1WT, Dyn1CC and Dyn1Closed to catalyze membrane fission and vesicle release from SUPER templates.",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(D) Size exclusion chromatographic profiles of Dyn1CC, Dyn1Closed at room temperature or after incubation for 10 min at 37°C.",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(F) Negative-stain electron micrographs of Dyn1WT, Dyn1ΔΔ and Dyn1Closed assembled onto lipid nanotubes. Scale bar = 200 nm",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(G) Curvature dependent liposome-stimulated GTPase activity of Dyn1WT and Dyn1ΔΔ.",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(H) Ability of Dyn1WT and Dyn1ΔΔ to catalyze membrane fission and vesicle release from SUPER templates.",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(A) Temperature dependence of basal and lipid stimulated GTPase activity of Dyn1WT and Dyn2S619L.",
    "ncbi_link": "Dyn1: 1759
Dyn2: 1785"
  },
  {
    "caption": "(B) Temperature sensitive membrane fission activity of Dyn1WT, Dyn2WT and Dyn2S619L measured using SUPER templates.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(C) Detection of Dyn2 PHD-stalk interactions by FRET using IAEDANS-labeled Dyn2L354C.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(D) Curvature dependent membrane binding and consequent opening of PHD in Dyn1Y354C-IAEDANS and Dyn2L354C-IAEDANS.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(E) Differential temperature dependence of PHD-stalk FRET for WT and S619L mutant Dyn2IAEDANS. Data are presented as relative FRET distances assuming a single donor/acceptor pair.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(F) Differential solvent exchange kinetics of Dyn1S619L at ambient temperature compared to Dyn1WT under identical conditions. Yellow coloring indicates a significant increase in HDX. Quantitative data on the individual peptides used to generate this map are provided in (Appendix Fig. S5).",
    "ncbi_link": "Dyn1: 1759"
  },
  {
    "caption": "(A,B) Transferrin receptor (TfnR) uptake, a measure of CME, shown as % uptake of total steady-state surface TfnR for control H1299 cells, and H1299 cells stabily expressing low amounts of siRNA-resistant Dyn2WT-EGFP (A) or Dyn2S619L-EGFP (B) with or without treatment of siRNA-directed towards endogenous Dyn2.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(C) Fixed cell TIRF-M images of Dyn2WT-EGFP or Dyn2S619L-EGFP expressing H1299 cells with or without Dyn2-siRNA treatment showing co-localization with clathrin light chain immunostained rabbit anti-CLC and Alexa 547-conjugated secondary antibodies.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(D) Percentage of Dyn2-EGFP positive clathrin coated pits detected by live cell TIRF-M and automated master/slave image analysis (Aguet et al, 2013).",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(E) Lifetime analysis of CCPs which are positive for EGFP-Dyn2WT or EGFP-Dyn2S619L with or without siRNA-mediated specific knockdown of endogenous Dyn2.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "C. The in vitro synthesized [35S]Met-labeled Bax E69C protein with or without the additional mutations (G108E and/or S184V) were activated by the in vitro synthesized [35S]Met-labeled tBid L105C protein and targeted to the Bax-/-/Bak-/- mitochondria that were pretreated with NEM. The resulting mitochondria were isolated and oxidized by CuPhe for 0 or 30 min. The resulting \"0 min\" samples (1 equivalent each) and \"30 min\" samples (1 equivalent each) were analyzed by non-reducing SDS-PAGE and phosphor-imaging. The remaining \"30 min\" samples (4 equivalent each) were immunoprecipitated (IP) by either Bax- or tBid-specific antibody, and then analyzed by non-reducing SDS-PAGE and phosphor-imaging. The identities of the four major products, indicated on the right side of the image, were based on their Mr and recognition by the respective antibody. n = 2.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "A-C. The single or double-cysteine Bax proteins with or without the indicated mutations were synthesized in vitro, activated by tBid protein and targeted to the Bax-/-/Bak-/- mitochondria. Cytochrome c release from the mitochondria was measured using ELISA. The dots are the fractions of cytochrome c release from two independent replicates after they were corrected as described in Figure EV1B, and the lines are the means. The amount of the Bax mutants bound to the mitochondria in the assay was determined and the results are shown in Appendix Figure S1.",
    "ncbi_link": "Bak: 12018"
  },
  {
    "caption": "B. Purified wild-type (WT) or mutant (G179I or T182I) Bax protein of the indicated concentration was incubated with the Bax-/-/Bak-/- mitochondria in the absence or presence of tBid protein. The proteins released from and those remaining in the mitochondria were separated and analyzed by SDS-PAGE and immunoblotting with antibody specific to either cytochrome c or Smac. n = 2.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "C. Purified wild-type or mutant Bax protein of the indicated concentration alone or together with purified cBid was incubated with the Bax-/-/Bak-/- mitochondria containing Smac-mCherry protein. Release of Smac-mCherry was detected by measuring the fluorescence in the supernatant after the mitochondria were pelleted by centrifugation. The dots are the fractions of Smac-mCherry release from three independent replicates, and the lines are the means.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "A-C. SPF C57BL/6Jmice were co-colonized with E1 and N1 wild type, (WT, A, n=5 mice) N1 T6SS mutant, (ΔtssC, B, n=4) or N1 complemented (ΔtssC pTssC, C, n=5). FecalCFU was quantified for E1 (closed squares) and N1 (open squares) weekly.",
    "ncbi_link": "tssC: 
TssC: "
  },
  {
    "caption": "D. Four weeks post-colonization, E1 fecal recovery was compared between the N1 WT, ΔtssC, and ΔtssC pTssC groups.",
    "ncbi_link": "tssC: "
  },
  {
    "caption": "B-E. Co-colonization of N1 WT (B and D, n=4 mice) or N1 Δbte2 (C, n=4) with E1 WT (B and C) or E1 overexpressing Bti2a (E1 pBti2a, D). FecalCFU was monitored over time (B-D) and E1 CFU compared to N1 WT-E1 WT group at four-weeks post co-colonization (E).",
    "ncbi_link": "bte2: 
Bti2a: "
  },
  {
    "caption": "A-F. Primary colonization of SPF mice with N2 WT, T6SS mutant (ΔtssC) and complemented (ΔtssC pTssC) followed by secondary challenge with N1 WT (A and B, n=5 mice) N2 WT (C and D, n=5) or E1 WT (E and F, n=4) was performed.A, C and E. FecalCFU for primary and secondary strains was determined for four weeks post-secondary challenge.B, D and F. Selected time points were tested for statistical difference of secondary challenge between groups. This includes four weeks post-secondary challenge (B) and three days post-challenge (D and F).",
    "ncbi_link": "tssC: "
  },
  {
    "caption": "A. Mice were co-colonized with E1 and either N1 WT (n=4) or N1 ΔtssC (n=3). Five days post-inoculation, fecal RNA was extracted and tested for BFT expression via qRT-PCR.",
    "ncbi_link": "tssC: "
  },
  {
    "caption": "B. Four weeks after co-colonization with E1 and either N1 WT or N1 ΔtssC (n= 4 mice per group), the sera were collected, tested via ELISA for anti-BFT IgG and end point titer calculated.",
    "ncbi_link": "tssC: "
  },
  {
    "caption": "C-F. Mice pre-treated with DSS were inoculated with no organisms (sham), E1 only, or E1 competed with N1 WT or N1 ΔtssC. Five days post-inoculation, the ceca were weighed (C) and fixed for histopathological examination after sham (D), E1 only (E) and E1-N1 WT (F) colonizations. Scale bars denote 100μm (main image) and 200μm (inset).",
    "ncbi_link": "tssC: "
  },
  {
    "caption": "(a) Western blot analysis of myosin-VI-depleted HeLa cells untreated or treated with 100 nM bafilomycin A1. (b) Quantification of western blot LC3-II intensity (±s.d.; n = 3). **P0.01, ***P0.001",
    "ncbi_link": "myosin-VI: 4646"
  },
  {
    "caption": "(c) Confocal immunofluorescence microscopy of LC3 punctae (green) in HeLa cells following knockdown of myosin VI. Hoechst labels the nuclei (blue). The insets show higher magnifications of the areas outlined in the main images (d) Quantification of LC3- and p62-positive punctae was performed and the results are represented as the average punctae fluorescence intensity per cell (±s.d.; n = 3) from >1,500 cells per experiment.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(e) Western blot analysis of parental HeLa cells or HeLa cells stably expressing siRNA-resistant GFP-myosin VI transiently transfected with a single myosin VI siRNA oligonucleotide following treatment with 1 μM MG132.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(l) Western blot (top) and confocal immunofluorescence microscopy (bottom) of mock- or myosin-VI-siRNA-treated HeLa cells stably expressing the RFP-GFP-LC3 reporter. Hoechst labels the nuclei (blue). (m) Quantitative data of RFP and GFP signal overlap from confocal images of mock- or myosin-VI-siRNA-treated HeLa cells expressing RFP-GFP-LC3. The data are represented as the Pearson's coefficient of the RFP and GFP signal correlation from >100cells per experiment (±s.d.; n = 3).",
    "ncbi_link": "myosin-VI: 4646"
  },
  {
    "caption": "n) Confocal immunofluorescence microscopy of myosin-VI-depleted RPE cells stably expressing GFP-LC3 immunostained against GFP (green) and cathepsin D (red). Hoechst labels the nuclei (blue). The insets show higher magnifications of the areas outlined in the main images. Scale bars, 20 μm. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "myosin-VI: 4646"
  },
  {
    "caption": "(a) RPE cells transiently transfected with siRNA against myosin VI and Atg5 were treated with 1 μM MG132 for 16 h. Cells were processed for immunofluorescence microscopy following 16 h MG132 treatment (zero time point) and 8 h post-washout of inhibitor. Immunolabelling for p62 was performed to visualize aggregates (red) and Hoechst was used to identify nuclei (blue).",
    "ncbi_link": "Atg5: 9474
myosin VI: 4646"
  },
  {
    "caption": "(c) Parental HeLa cells or HeLa cells stable expressing siRNA-resistant GFP-myosin VI were transiently transfected with a single siRNA oligonucleotide targeting myosin VI and were subsequently treated with 1 μM MG132 for 16 h. Cells were processed for immunofluorescence microscopy at 16 h post-MG132 treatment (t = 0) or allowed to recover following washout of MG132 for 8 h (t = 8). Cells were processed for quantification with the automated Cellomics VTi microscope to evaluate the p62 fluorescence intensity. The results represent the fold increase in p62 fluorescence intensity of myosin VI siRNA compared with mock control cells following recovery from MG132 washout (t = 8; ±s.d.; n = 3).",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(d) HeLa cells with stable expression of HttQ72-GFP were transiently transfected with siRNA against myosin VI followed by saponin extraction and processing for immunofluorescence microscopy. Immunolabelling was performed for GFP (green) and p62 (red). Nuclei are labelled with Hoechst (blue). (e) Quantification of HttQ72-GFP aggregates was performed on myosin-VI-siRNA-transfected HeLa cells. The results were calculated as the percentage of GFP-expressing cells with greater than 15 GFP-positive spots per cell. The results represent the mean (±s.d.) from n = 3independent experiments, ***P0.001. The insets show higher magnifications of the areas outlined in the main images. Scale bars, 20 μm. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "Htt: 3064
myosin VI: 4646"
  },
  {
    "caption": "(b) RPE cells with stable expression of cherry-LC3 were transiently transfected with the GFP-myosin VI cargo-binding tail domain containing various mutations in the protein-interaction (ΔWWY and ΔRRL) and ubiquitin-binding motifs (A1013G), followed by treatment with 250 nM Torin1 for 3 h to induce autophagy. Immunofluorescence microscopy was performed either in the absence or presence of saponin extraction. The arrowheads indicate areas of co-localization. Scale bar, 20 μm. (c) A Pearson's coefficient was calculated on the basis of the degree of co-localization between the different GFP-myosin VI mutant tails and cherry-LC3 from confocal immunofluorescence micrographs. The graph represents data from more than 20 transfected cells from n = 2 independent experiments.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(b) Binding of myosin VI to Tom1 requires the WWY motif. Bottom, the mammalian two-hybrid assay was used to test binding of full-length Tom1 and Tom1L2 or various truncated versions of Tom1, annotated by amino acid numbers, against wild-type myosin VI tail or the myosin VI ΔWWY or ΔRRL tail. The graph shows the mean values from n = 2 independent experiments. Top, Tom1 domain structure and truncation mutants. VHS, Vps-27, Hrs and STAM; GAT, GGA and Tom1.",
    "ncbi_link": "myosin VI: 4646
Tom1: 10043"
  },
  {
    "caption": "(c) RPE cells stably expressing GFP-myosin VI were processed for immunofluorescence microscopy to evaluate GFP-myosin VI and endogenous Tom1/Tom1L2 or Rab5 co-localization. The insets show higher magnifications of the areas outlined in the main panels. The arrows indicate areas of co-localization.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(d) RPE cells with stable expression of GFP-myosin VI tail were subjected to mock or Tom1 siRNA transfection followed by western blot analysis (left) and immunofluorescence microscopy (middle) to evaluate GFP-myosin VI tail localization. Cells were either fixed directly or saponin-extracted before fixation. Quantification (right) was performed on RPE cells stably expressing GFP-myosin VI tail and transfected with mock, Tom1 or TNO siRNA. Cells were processed for immunocytochemistry, immunolabelled for GFP and nuclei labelled with Hoechst followed by quantification of GFP-myosin VI tail punctae per cell using an automated Cellomics VTi microscope. More than 600 cells per group from n = 3 independent experiments were analysed and are represented as the mean number of GFP-myosin VI tail punctae per cell (±s.d.). Scale bars, 20 μm. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "myosin VI: 4646
Tom1: 10043"
  },
  {
    "caption": "(a) HeLa cells transiently transfected with siRNA against Tom1 were left untreated or treated with 100 nM bafilomycin A1 for 4 h. Western blot analysis was performed on whole-cell lysates against the indicated proteins. (b) Quantification of LC3-II intensity of western blots was performed by an infrared imaging system. (±s.d.; n = 3). *P0.05, **P0.01.",
    "ncbi_link": "Tom1: 10043"
  },
  {
    "caption": "(c, left) Confocal immunofluorescence microscopy was performed on HeLa cells transfected with Tom1 siRNA to evaluate LC3 punctae formation (green). The insets show higher magnifications of the areas outlined in the main images. Nuclei are labelled with Hoechst (blue). (c,right,d) Quantification of LC3-positive punctae (c, right) and p62-positive punctae (d) was performed in a 96-well format on an Arrayscan VTi HCS microscope. Cells were identified by Hoechst staining of nuclei (blue). The results are represented as the average punctae fluorescence intensity per cell (±s.d.) from n = 3 independent experiments each performed in triplicate wells, each with >500 cells.",
    "ncbi_link": "Tom1: 10043"
  },
  {
    "caption": "(c, left) Confocal immunofluorescence microscopy was performed on HeLa cells transfected with Tom1 siRNA to evaluate LC3 punctae formation (green). The insets show higher magnifications of the areas outlined in the main images. Nuclei are labelled with Hoechst (blue). (c,right,d) Quantification of LC3-positive punctae (c, right) and p62-positive punctae (d) was performed in a 96-well format on an Arrayscan VTi HCS microscope. Cells were identified by Hoechst staining of nuclei (blue). The results are represented as the average punctae fluorescence intensity per cell (±s.d.) from n = 3 independent experiments each performed in triplicate wells, each with >500 cells.",
    "ncbi_link": "Tom1: 10043"
  },
  {
    "caption": "(f) Confocal immunofluorescence microscopy of Tom1-depleted RPE cells stably expressing GFP-LC3 immunostained against GFP (green) and cathepsin D (red). Hoechst labels the nuclei (blue). The insets show higher magnifications of the areas outlined in the main images.",
    "ncbi_link": "Tom1: 10043"
  },
  {
    "caption": "(g) HeLa cells with stable expression of HttQ72-GFP were transiently transfected with Tom1 siRNA (top right), saponin-extracted, and processed for immunofluorescence microscopy (left) to quantify HttQ72-GFP punctae (bottom right). Immunolabelling against GFP (green) and p62 (red) was performed. Nuclei (blue) were labelled with Hoechst. The results are represented as the number of GFP-expressing cells with greater than 15 GFP-positive spots per cell (±s.d.; n = 3). Scale bars, 20 μm. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "Htt: 3064
Tom1: 10043"
  },
  {
    "caption": "(a) Left, RPE cells with stable expression of GFP-LC3 following mock- or myosin-VI-siRNA transfection were processed for confocal immunofluorescence microscopy and immunolabelled for Tom1/Tom1L2 (red). Nuclei (blue) were labelled with Hoechst. The insets show higher magnifications of the areas outlined in the main panels and the arrows highlight areas of complete overlapping co-localization and arrowheads highlight adjacent localization of Tom1 relative to LC3. Right, quantification was performed on >75 cells for the relative position (adjacent or complete overlap) of Tom1-positive vesicles in relation to LC3-positive vesicles. The results are represented as the average number of Tom1-positive vesicles per cell categorized by their relative position to LC3 (±s.d.; n = 3).",
    "ncbi_link": "myosin-VI: 4646"
  },
  {
    "caption": "(b) GFP-LC3-expressing RPE cells were depleted of myosin VI by siRNA. Cells were pulse labelled with Texas-red-dextran (red) for 4 h, before chase into fresh medium containing 1 μM MG132 for 2 h. Cells were processed for immunofluorescence microscopy and immunostained for GFP (green). Nuclei were labelled with Hoechst (blue). The insets represent higher magnifications of the areas outlined in the main panels. (c) Mander's overlap coefficients for the degree of LC3 signal co-localizing with dextran were calculated using Volocity software. The results represent >20 cells from n = 3 independent experiments and are illustrated as a box and whisker plot. The box represents the median, 25th and 75th percentiles and whiskers represent the maximum and minimum.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(d) RPE cells stably expressing GFP-LC3 were depleted of myosin VI and Tom1 by siRNA. Cells were pulse-labelled with Texas-red (TR)-dextran for 16 h followed by a chase period of 4 h. Cells were processed for immunoelectron microscopy and labelled with 15 nm gold particles against GFP-LC3 and 5 nm gold particles against Texas-red-dextran. Scale bars, 20 μm (a,b); 200 nm (d).",
    "ncbi_link": "myosin VI: 4646
Tom1: 10043"
  },
  {
    "caption": "(A) MYB knockdown (MiaPaCa-shMYB and Panc1-shMYB) and forced MYB-overexpressing (BxPC3-MYB) PC cells along with their respective control cell lines (MiaPaCa-Scr, Panc1-Scr, and BxPC3-Neo) were subjected to hypoxia (1% O2) treatment for different time intervals (0-96 h). Their growth was measured by viable cell counting using a trypan blue exclusion assay.",
    "ncbi_link": "Neo: 
MYB: 4602"
  },
  {
    "caption": "(E, F) ECAR (E) and OCR (F) in control and MYB silenced MiaPaCa cells cultured under normoxia or treated with hypoxia mimetic CoCl2 (100 μM for 4 h). Thereafter, ECAR was measured in PC cells with sequential injection of glucose, oligomycin, and 2-DG, while OCR was measured with the serial addition of oligomycin, FCCP, and antimycin A/rotenone.",
    "ncbi_link": "MYB: 4602"
  },
  {
    "caption": "(E) Pancreatic cancer cells were transiently transfected either with non-targeted control siRNA (siCtrl) or HIF1α -targeting siRNA (siHIF1α) for 24 h and then incubated under hypoxia for 6 h. MYB expression was analyzed at protein and mRNA levels.",
    "ncbi_link": "HIF1α: 3091"
  },
  {
    "caption": "(G) Cells transfected with HuR or control siRNA for 48 h were exposed to hypoxia for 6 h, and MYB and HuR expression was determined by immunoblotting or qRT-PCR.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(A) MYB-silenced (MiaPaCa-shMYB and Panc1-shMYB) and MYB-overexpressing (BxPC3-MYB) PC cells, along with their control cell lines (MiaPaCa-Scr, Panc1-Scr, and BxPC3-Neo) were exposed to hypoxia for 6 h. Protein lysates were made, and the expression of MYB and HIF1α was examined by immunoblotting. β-actin served as a loading control.",
    "ncbi_link": "Neo: 
MYB: 4602"
  },
  {
    "caption": "(C) The transcriptional activity of the HIF1α promoter was determined by performing the promoter-reporter assay. MYB-modulated PC cell lines were transfected with the reporter plasmid, and after 24 h of transfection, cells were cultured under hypoxia or normoxia for 24 h, and the supernatant was collected. HIF1α promoter-driven Gaussia luciferase activity was normalized with SEAP activity, and the data was presented as a bar diagram.",
    "ncbi_link": "HIF1α: 3091
MYB: 4602"
  },
  {
    "caption": "(E) MYB-silenced or -overexpressing PC cell lines were exposed to normoxia or hypoxia for 6 h and subjected to chromatin immunoprecipitation using anti-MYB antibodies or IgG control followed by qPCR analysis using site-specific primers.",
    "ncbi_link": "MYB: 4602"
  },
  {
    "caption": "(A) Immunoblot analysis was performed to analyze HIF1α and MYB expression in MYB-silenced (shMYB) and those having a forced overexpression of HIF1α (shMYB-HIF1αOE) along with their respective controls (Scr and shMYB-Neo) cultured under hypoxia. β-actin served as a loading control.",
    "ncbi_link": "Neo: 
HIF1α: 3091
MYB: 4602"
  },
  {
    "caption": "(C) Live/Dead staining was performed in MYB-silenced MiaPaCa and Panc-1 or MYB silenced- HIF1α overexpressed cells cultured under hypoxia for 48 h. Cells were visualized under a fluorescence microscope. Representative fluorescence micrographs are presented. The number of live and dead cells was counted from the captured random images. Scale bar, 150 μm (lower right corner).",
    "ncbi_link": "HIF1α: 3091
MYB: 4602"
  },
  {
    "caption": "(F) MYB-silenced and HIF1α overexpressing MYB knockdown PC cells and control cells were cultured under hypoxia for 48 h. Conditioned media was collected and analyzed to assess glucose consumption and lactate secretion by measuring their levels. The data was normalized with the number of cells and presented as relative fold changes.",
    "ncbi_link": "HIF1α: 3091
MYB: 4602"
  },
  {
    "caption": "(C) Quantitative ChIP-qPCR was performed to analyze the occupancy of MYB under normoxia and hypoxia at promoter regions of selected glycolytic genes (GLUT3, HK2, PFKL, ENO2, and MCT4) using anti-MYB or IgG control antibodies. The enrichment of promoter regions was compared between cells cultured under normoxia or hypoxia.",
    "ncbi_link": "ENO2: 2026
HK2: 3099
MYB: 4602
PFKL: 5211
MCT4: 9122
GLUT3: 6515"
  },
  {
    "caption": "E. PEBP1 protein levels were measured by Western blot after knock out in C11 cells by LvPEBP1-sg1. Mock C11 cells served as control.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "A. PEBP1 expression was measured by qPCR (left panel) and Western blot (right panel) in the latently infected C11 cells and the parental Jurkat cells.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "Effect of PEBP1 on the Raf1/ERK/IκB and IKK/IκB/NF-κB signaling pathways. The levels of indicated proteins in total protein lysates (C) were analysed by Western blot in C11-PEBP1-KO cells and mock C11 cells.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "Effect of PEBP1 on the Raf1/ERK/IκB and IKK/IκB/NF-κB signaling pathways. the levels of NF-κB/p65 protein in nucleus (D) were analysed by Western blot in C11-PEBP1-KO cells and mock C11 cells.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "F. The impact of PEBP1 on the activation of the HIV LTR was explored by luciferase reporter assay in 293T cells. 293T cells were co-transfected with PEBP1-sg1 alone or PEBP1-sg1 with HIV-1 LTR-empty plasmids, HIV-1 wild type LTR-luciferase plasmids, HIV-1 LTR-Δsp1-luciferase, HIV-1 LTR-ΔNF-κB-luciferase, HIV-1 LTR-ΔAp1-luciferase or HIV-1 LTR-ΔYY1-luciferase. Transcription of HIV-1 was determined by luciferase reporter assay.",
    "ncbi_link": "luciferase: 
Ap1: 3725
NF-κB: 4790///4791
PEBP1: 5037
sp1: 6667
YY1: 7528"
  },
  {
    "caption": "A. The expression of PEBP1 was analysed by Western blot in TZM-bl cells infected with mock, Lv-PCDH-empty or Lv-PCDH-PEBP1 plasmids.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "Overexpression of PEBP1 suppressed HIV-1 replication. TZM-bl cells were transfected with Lv-PCDH-empty or Lv-PCDH-PEBP1 followed by infection of HIV derived from patient plasma whose viral load is 129 copies/ml. The transcription of HIV-1 was evaluated 72 h post-infection by luciferase activity",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "Overexpression of PEBP1 suppressed HIV-1 replication. TZM-bl cells were transfected with Lv-PCDH-empty or Lv-PCDH-PEBP1 followed by infection of HIV derived from patient plasma whose viral load is 129 copies/ml. levels of p24 in the supernatants (C).",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "E. Induction of PEBP1 by EGCG or DHA in HIV-1 infected primary CD4+ T cells. Primary CD4+ T cells from healthy donors were treated with 10 μM EGCG or DHA during HIV-1 infection. Similar to Panel B, HIV-1 was isolated from the blood supernatants of patients receiving ART with a viral load of 129 copies/ml. Seventy-two hours post-treatment with 10 µM EGCG or DHA, the expression of PEBP1 was detected by qPCR.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "F. The induction of PEBP1 by EGCG or DHA suppressed HIV replication in the primary CD4+ T cells. The primary CD4+ T cells from healthy donors were treated with 10 μM EGCG or DHA during HIV-1 infection. Similar to Panel B and E, HIV-1 was isolated from the blood supernatants of patients receiving ART with a viral load of 129 copies/ml. The supernatants from HIV-1-infected CD4+ T cell were collected 1, 2, 3 or 4 days post-infection. Replication of HIV-1 was analyzed by p24 ELISA.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "B. PEBP1 mRNA was induced by EGCG in patient primary CD4+ T cells. Primary CD4+ T cells were treated with 10 μM EGCG. The expression of PEBP1 in the cells was measured by qPCR.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "C. After infection with VSV-G pseudotyped HIV-1 NL4.3-nanoluc, the mRNA expression of PEBP1 was measured by qPCR.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "Jurkat CD4+ T cells were treated with IFN-α, IFN-β and IFN-γ for 24 h. The mRNA expression levels of PEBP1 were measured by qPCR",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "F. PEBP1 knockout enhanced HIV-1 transcription in the primary CD4+ T cell model of latency. The expression of HIV-1 was measured by nanoluc after gene knockout where α-CD3/CD28 stimulation served as a positive control.",
    "ncbi_link": "PEBP1: 5037"
  },
  {
    "caption": "(A) Race tube assays with FRH mutants. Every circadian cycle N. crassa lays down aerial hyphae that appear as fluffy yellow/orange conidial bands. The distance between the bands reflects the clock period. The strains were grown in constant darkness and growth fronts were labeled every 24 h (black vertical lines), rhythmicity on right (τ= period in hours, σ = standard deviation, n = number of race tubes, ARR, arrhythmic). The race tubes shown here are representative samples from three replicate tubes.",
    "ncbi_link": "FRH: 3872445"
  },
  {
    "caption": "(B) Pull-down assays evaluating interactions among FRH, FRQ, WC-1 and WC-2. Ratio of FRQ, WC-1 and WC-2 binding to the V5 tagged FRH mutants as compared to the inter-strain variations in FRH levels, error bars represent standard deviation for the assay run in triplicate. *P < 0.05 (unpaired two-tailed t-test with Gaussian distribution assumption). Representative immunoblots are shown in Appendix Fig S5.",
    "ncbi_link": "FRH: 3872445"
  },
  {
    "caption": "A B16F10 melanoma cells with either mTRF2 overexpression or knockdown were inoculated into the backs of immunocompetent mice. The percentages of intratumoral CD11bHi GR1Hi MDSCs (n = 10 mice), CD25+ Foxp3+ regulatory T cells (Tregs), or CD25+ Foxp3− activated T cells (n = 5 mice per group) among CD45+ cells were analyzed by fluorescence-activated cell sorting (FACS) and represented as box plots Data information: data are presented by Box plots Min to Max showing all points with median. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Mann-Whitney test.",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "TRF2-overexpressing or -knockdown BJcl2 cells were inoculated into the backs of immunodeficient mice in the presence of Matrigel. Five days later, the percentage of immune cells infiltrating the Matrigel plugs of CD11bHi GR1Hi MDSCs (C) were determined by FACS (n = 5 mice per group).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "TRF2-overexpressing or -knockdown BJcl2 cells were inoculated into the backs of immunodeficient mice in the presence of Matrigel. Five days later , the intranuclear staining of pSTAT3 (D) were determined by FACS (n = 5 mice per group).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "TRF2-overexpressing or -knockdown BJcl2 cells were inoculated into the backs of immunodeficient mice in the presence of Matrigel. Five days later, CD3− NKp46+ and IFN-γ+ among CD3− NKp46+ NK cells (E) were determined by FACS (n = 5 mice per group).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "Linear correlation plot of the percentage of IFN- γ + NK cells, the mean of fluorescence intensity (MFI) of pSTAT3 for MDSCs, and the expression of TRF2 (r2= 0,5177; Pearson's correlation, p = 0.003) (F) Data information: data are presented by Box plots Min to Max showing all points with median. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Mann-Whitney test. Pearson correlation and p values are indicated.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "the mRNA expression level in the matrigel plugs of arg1, pSTAT3 MFI and TRF2 expression (r2= 0,7077; Pearson's correlation, p < 0.0001) (G); the mRNA expression level in the matrigel plugs of tgfβ, pSTAT3 MFI and TRF2 expression (r2= 0,3669; Pearson's correlation, p = 0.0046) (H) and the mRNA expression level in the matrigel plugs of il-10, pSTAT3 MFI and TRF2 expression (r2= 0,7418; Pearson's correlation, p < 0.0001) (I). Data information: data are presented by Box plots Min to Max showing all points with median. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Mann-Whitney test. Pearson correlation and p values are indicated.",
    "ncbi_link": "arg1: 11846
il-10: 16153
TRF2: 7014
tgfβ: 21803"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into the backs of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP). The tumor volume was determined every 2 days using hemi-ellipsoid formula (B). Tumor volume are presented in mm3 along the time in days. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into the backs of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP). On day 19 of the tumor growth experiment, the percentages of GFP+ cells infiltrating the lungs were determined by FACS and presented as the number of GFP+ cells/mg lung tissue (C). Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "ncbi_link": "GFP: 
TRF2: 21750"
  },
  {
    "caption": "B16F10 melanoma cells with or without mTRF2 overexpression were inoculated into tail vein of immunocompetent mice and treated with anti-GR1 antibody or isotypic control (200µg/IP) every 3 days. On day 21, lung metastasis was analyzed by hematoxylin and eosin (H&E) staining F), scale bars = 500µM. Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "BJcl2 cells with or without hTRF2 overexpression were inoculated into the backs of immunodeficient Nude mice and treated with anti-GR1 antibody or isotypic control (200µg/IP) and NK cells recruitment, degranulation and MDSC infiltration were monitored by FACS Density plot of CD11bHi GR1Hi MDSC staining in control or anti-GR1-treated Matrigel plugs (K).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "BJcl2 cells with or without hTRF2 overexpression were inoculated into the backs of immunodeficient Nude mice and treated with anti-GR1 antibody or isotypic control (200µg/IP) and NK cells recruitment, degranulation and MDSC infiltration were monitored by FACS Box plots of the percentages of infiltrating or activated NK cells (CD107a or CD69) (L) Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "BJcl2 cells with or without hTRF2 overexpression were inoculated into the backs of immunodeficient Nude mice and treated with anti-GR1 antibody or isotypic control (200µg/IP) and NK cells recruitment, degranulation and MDSC infiltration were monitored by FACS Box plots of the percentages of CD11bHi GR1Hi MDSC or NKp46+ NK cells (M) infiltrating the Matrigel plugs assay among the CD45+ cells. Data information: data are presented by Box plots Min to Max showing all points with median corresponding to the percentages of each cell population among CD45+ cells or the indicated parent population or the number of lung nodules. All experiments are performed with n = 8 mice per group; *p < 0.05, **p < 0.01, and ***p < 0.001; Mann-Whitney test.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "Analysis of STAT3 phosphorylation by MSC2 cells after 18 hours' co-culture with BJcl2 overexpressing or compromised for TRF2 Histograms of the pSTAT3 mean fluorescence intensity (MFI) (B).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "+/- inhibitors: anti-mouse IL-6 or JAK1/2 inhibitor (Ruxolitinib) in (E).",
    "ncbi_link": "JAK1: 16451"
  },
  {
    "caption": "TRF2-overexpressing or -knockdown BJcl2 cells were co-cultured with MSC2 cells for 18h +/- mouse IL6 blocking antibody or Ruxolitinib. After FACS sorting, MSC2 cells were co-cultured for 18h with primed and purified NK cells before a 4h challenge with YAK-1. NK cell degranulation and IFN-γ production were analyzed by FACS (G). Data information: Panels show all points with mean ± SEM corresponding to the percentages of each cell population among NK cells (G) (n = 3 independent experiments; *p < 0.05, **p < 0.01, and ***p < 0.001; Student's t-test).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "TRF2-overexpressing or -knockdown BJcl2 cells were co-cultured with MSC2 cells for 18h +/- mouse IL6 blocking antibody or Ruxolitinib. Alternatively, a 4h challenge with NIH3T3 cells was performed and the ability of NK cells to kill NIH3T3 cells were determined by colorimetric analysis (AlamarBlue) (H). Data information: Panels show all points with mean ± SEM corresponding to the percentage of specific target lysis (H) (n = 3 independent experiments; *p < 0.05, **p < 0.01, and ***p < 0.001; Student's t-test).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "Gene expression analysis by quantitative polymerase chain reaction (qPCR) of TRF2 target genes following TRF2 overexpression or knockdown. Data information: data represent n = 3 independent experiments with mean ± SEM",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "D Specific qPCR for HS3SH4, GPC6, and VCAN ITSs after ChIP using an anti-H3K27ac antibody in TRF2-overexpressing or -knockdown BJcl2 cells. Data represent fold enrichment of the H3K27ac level compared with the total H3 level. Data information: data represent n = 3 independent experiments with mean ± SEM",
    "ncbi_link": "GPC6: 10082
HS3SH4: 9951
TRF2: 7014
VCAN: 1462"
  },
  {
    "caption": "Histograms of the pSTAT3 mean fluorescence intensity (MFI) of MSC2 cells when TRF2 was overexpressed and the target gene knocked down (G) Data information MFI of n=3 independent experiment is normalized to controls and represented as fold change of MFI (n = 3 independent experiments; *p < 0.05 and **p < 0.01; Student's t-test).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "Histograms of the pSTAT3 mean fluorescence intensity (MFI) of MSC2 cells when both TRF2 and its target gene were knocked down (H). Data information: MFI of n=3 independent experiment is normalized to controls and represented as fold change of MFI (n = 3 independent experiments; *p < 0.05 and **p < 0.01; Student's t-test).",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "I Histograms of tumor weights on day 19 after implantation of subcutaneous xenografts containing BJcl2 cells overexpressing or knocked down for HS3ST4 or GPC6 Data information: data are represented as mean +/- SEM (n = 8 mice per group; *p < 0.05, and **p < 0.01; Mann-Whitney test).",
    "ncbi_link": "GPC6: 10082
HS3ST4: 9951"
  },
  {
    "caption": "C AFM images showing the Modulus heatmap (stiffness) in GFP-expressing or TRF2-overexpressing cancer cells. At each of the 128x128 force curve points, corresponding to an area of 10 μm2, the AFM software automatically displays the Sneddon modulus analysis while scanning the sample. The color bar on the left of the images shows a qualitative representation of the elastic map.",
    "ncbi_link": "GFP: 
TRF2: 7014"
  },
  {
    "caption": "D Analysis of pSTAT3 levels in MDSCs after co-culture with GFP-expressing or TRF2-overexpressing cancer cells treated with or without sodium chlorate (NaClO3). Data information: In (D), data represents mean of n = 3 independent experiments +/- SEM (***p < 0.001; Student's t-test).",
    "ncbi_link": "GFP: 
TRF2: 7014"
  },
  {
    "caption": "A Kaplan-Meier curves for overall survival of chemotherapy-treated patients according to the TRF2 expression level Data information: the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "Immunocompetent mice were subcutaneously engrafted with B16F10 cells with or without TRF2 overexpression and treated with three intraperitoneal injections of 50 mg/kg 5-FU. The tumor volume was determined every 2 days using a caliper, and growth curves over time (C) Data information: , data represent mean values +/- SEM (n = 8 mice per group; *p < 0.05 and **p < 0.01; Mann-Whitney test).",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "Immunocompetent mice were subcutaneously engrafted with B16F10 cells with or without TRF2 overexpression and treated with three intraperitoneal injections of 50 mg/kg 5-FU. tumor volume were determined on day 19 and represented using Box plots Min to Max showing all points with median (D). Data information: (D), data are represented by Box plots Min to Max showing all points with median (n = 8 mice per group; *p < 0.05 and **p < 0.01; Mann-Whitney test)",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "Immunocompetent mice were subcutaneously engrafted with B16F10 cells with or without TRF2 overexpression and treated with three intraperitoneal injections of 50 mg/kg 5-FU. Overall survival was also determined (E).",
    "ncbi_link": "TRF2: 21750"
  },
  {
    "caption": "A Kaplan-Meier curves for overall survival of patients at all stages of cancers (breast, gastric, ovarian, and lung cancer) depending on TRF2 expression level. Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "The overall survival of gastric cancer patients (all stages) was analyzed depending on TRF2 and its targets genes expression level (HS3ST4, GPC6 and VCAN collectively named the HSPG genes) Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "ncbi_link": "GPC6: 10082
HS3ST4: 9951
TRF2: 7014
VCAN: 1462"
  },
  {
    "caption": "F Overall survival of gastric cancer patients (all stages) analyzed depending on TRF2, HSPG genes (HS3ST4, GPC6 and VCAN) and MDSC level (Lo or Hi). Data information: For all panels, the optimal cut-off is determined on KMplot. The p value (log Rank test), the Hazard Ratio and number of patients are indicated.",
    "ncbi_link": "GPC6: 10082
HS3ST4: 9951
VCAN: 1462"
  },
  {
    "caption": "TLR9-deficient mice were analysed 10 weeks after TAC (e, f). e, Scale bars, 0.2 s and 5 mm. f, Echocardiographic parameters (n = 6-10 per group). Data are mean ± s.e.m. *P  0.05 versus all other groups.",
    "ncbi_link": "TLR9: 81897"
  },
  {
    "caption": "(C) CRIP1  mRNA expression  in the TCGA-LIHC  dataset. (D) mRNA levels of CRIP1  in the GSE36376 dataset from the GEO database. Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05, **P < 0.01, and ***P < 0.001. Differences were tested using a two-tailed, unpaired Student's t-test",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(B) Tumor sphere formation assay in CRIP1-overexpressing Huh7  and Hep3B  cells. The data are shown as the relative fold change spheres  compared with the vector group (right). Scale bar: 50 μm. Data information: Data represent the mean ± SD at least three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001. Differences were tested using an unpaired 2-tailed Student's t-test (B,",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(C)  Western blot  analysis of HCC  cancer  stem cell  markers in CRIP1-overexpressing Huh7  and Hep3B  cells.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(H) Tumor sphere formation assay in CRIP1-knockdown MHCC-97H and HepG2  cells. The data are shown as the relative fold change spheres  compared with the siCtrl group (right). Scale bar: 50 μm. Data information: Data represent the mean ± SD at least three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001. Differences were tested using an unpaired 2-tailed Student's t-test H,",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(I) Western blot analysis of HCC  cancer stem cell markers in CRIP1-knockdown MHCC-97H and HepG2  cells.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(A) Western blot  analysis of BBOX1  protein levels in CRIP1-overexpressing Huh7  and Hep3B  cells. (B) Western blot analysis of BBOX1  protein levels in CRIP1  knockdown MHCC-97H and HepG2  cells.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(D) Western blot  analysis of BBOX1  in CRIP1-overexpressing Huh7  cells treated with CHX  (100 μg/ml) for the indicated durations (lfte). The graph shows quantification of relative BBOX1  levels (right). Data information: Data represent the mean ± SD of at least three independent experiments. *P < 0.05 and **P < 0.01. Differences were tested using an unpaired 2-tailed Student's t-test D).",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(E) Western blot  analysis of BBOX1  protein levels in CRIP1-overexpressing Huh7  and Hep3B  cells treated with MG132  (10 μM) for 10 h. D).",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(F) Co-immunoprecipitation and immunoblot  analyses of BBOX1 ubiquitination in CRIP1-overexpressing Huh7  and Hep3B  cells.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(G) Co-immunoprecipitation  and immunoblot  analyses of BBOX1 ubiquitination  in CRIP1-overexpressing Huh7  and Hep3B  cells transfected with STUB1  siRNAs.",
    "ncbi_link": "CRIP1: 1396
STUB1: 10273"
  },
  {
    "caption": "(J) Co-immunoprecipitation and immunoblot  analyses of the interaction  between STUB1  and BBOX1  and BBOX1 ubiquitination  in Huh7  cells transfected with STUB1-Myc  and CRIP1  siRNAs.",
    "ncbi_link": "Myc: 
CRIP1: 1396
STUB1: 10273"
  },
  {
    "caption": "(B) Co-immunoprecipitation and immunoblot  analyses of BBOX1 ubiquitination  in STUB1-overexpressing Huh7  and Hep3B cells transfected with BBOX1-WT or BBOX1  K240R mutant.",
    "ncbi_link": "BBOX1: 8424
STUB1: 10273"
  },
  {
    "caption": "(C) Western blot  analysis of BBOX1-WT or K240R mutant protein expression in Huh7  and Hep3B  cells transfected with increasing amounts of STUB1.",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "tumor sphere formation ability and quantification of spheres (E), in STUB1-overexpressing Huh7  and Hep3B  cells transfected with BBOX1-WT or BBOX1  K240R mutant. Scale bar: 50 μm. Data information: Data represent the mean ± SD of at least three independent experiments. **P < 0.01 and ***P < 0.001. Differences were tested using an unpaired 2-tailed Student's t-test",
    "ncbi_link": "BBOX1: 8424
STUB1: 10273"
  },
  {
    "caption": "protein levels  of HCC  cancer stem cell markers (G) in STUB1-overexpressing Huh7  and Hep3B cells transfected with BBOX1-WT or BBOX1  K240R mutant.",
    "ncbi_link": "BBOX1: 8424
STUB1: 10273"
  },
  {
    "caption": "Representative images of  tumor sphere formation and quantification of spheres (C) in CRIP1-overexpressing Huh7  cells with or without iCRT3  (50 μM) for 24 h. Scale bar: 50 μm. Data information: Data represent the mean ± SD of at least three independent experiments. **P <0.01 and ***P < 0.001. Differences were tested using an unpaired 2-tailed Student's t-test",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(E) Western blot  analysis of HCC  cancer stem cell  markers in CRIP1-overexpressing Huh7  cells with or without iCRT3  (50 μM) for 24 h.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(F) Coimmunoprecipitation and immunoblot  analyses of β-catenin acetylation in CRIP1  knockdown MHCC-97H cells treated with mildronate  (5 mM) for 24 h.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(G) Western blot analysis of cytoplasmic  and nuclear  fractions of  β-catenin in CRIP1  knockdown MHCC-97H cells treated with mildronate  (5 mM) for 24h.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "(I)  Co-immunoprecipitation and immunoblot  analyses of β-catenin ubiquitination  in CRIP1  knockdown MHCC-97H cells treated with mildronate  (5 mM) and EX527  (20 μM) for 24 h.",
    "ncbi_link": "CRIP1: 1396"
  },
  {
    "caption": "D. Western blot analysis of NIH3T3 cells that had been transfected with a pRK5-RAGC-HA-GST expression plasmid or control vector and treated with EVs or PBS for 48 h, and then labeled with Puro.",
    "ncbi_link": "GST: 
HA: 
RAGC: 64121"
  },
  {
    "caption": "C. Dual luciferase assay of the psiCHECK reporters containing the 3'UTR of RRAGC that was wild-type, with all three miR-105 sites mutated, or with the miR-204 site mutated. NIH3T3 cells were co-transfected with the reporter and indicated miRNA mimic (n=3 biological replicates for each group).",
    "ncbi_link": "miR-105: 406898///406897
miR-204: 406987
RRAGC: 64121"
  },
  {
    "caption": "A,B. A breast cancer tissue array was analyzed for correlations among RagC, miR-105, and miR-204 in tumor stroma by IHC/ISH-determined scores. Representative IHC and ISH images (A) and correlations determined by Kendall's tau correlation tests (N=24 independent tumors; Kendall's tau and two-sided P value as indicated) (B) are shown. Bar=200 μm.",
    "ncbi_link": "miR-105: 406897///406898
miR-204: 406987"
  },
  {
    "caption": "C,D. Xenograft mammary tumors formed from MCFDCIS cells overexpressing miR-105 or empty vector were collected from NSG mice for RagC IHC (n=5 tumors for each group). The relative intensity of RagC stain in tumor stroma was quantified by ImageJ. Bar=50 μm. In (D), data are presented as mean ± SD. *P<0.05 (Student's t-test).",
    "ncbi_link": "miR-105: 406897///406898"
  },
  {
    "caption": "C. Binding assay using MBP fused Apc1-loop500 fragments and B56γ. Apc1-loop500 WT or its derivatives (∆11 or 3A) were incubated with the 35S-labelled Flag-B56γ in interphase extract (Inter) or anaphase extract (Ana) supplemented with CycB∆167 at 23˚C for 1 hr. The bound proteins were recovered by amylose beads, separated by SDS-PAGE and detected by autoradiography or coomassie brilliant blue (CBB) staining. The bar graph is quantification of bound B56γ. The intensities of MBP control were arbitrarily set to 1.0. Error bars, s.e.m. from three independent experiments.",
    "ncbi_link": "Flag: "
  },
  {
    "caption": "(E) In vivo analyses of the Atg12 and Atg5 mutants for studying the functional significance of the non‐covalent Atg12‐Atg5 interactions. Yeast cells with or without starvation were lysed and subjected to urea SDS-polyacrylamide gel electrophoresis (PAGE) followed by western blotting. Ape1, aminopeptidase I; mApe1, mature form of Ape1; PE, phosphatidylethanolamine; prApe1, preform of Ape1; WT, wild‐type.",
    "ncbi_link": "Atg12: 852518
Atg5: 855954"
  },
  {
    "caption": "(A) Co-localization of c-terminally GFP- or mCherry-tagged Apl5, Sec7 and Vps41 in a vam3 temperature sensitive (ts) background strain. Cells were grown over night at 23°C and where indicated shifted to 37°C for 3 h prior to imaging. White arrowheads indicate co-localization events. Scale bar, 5 µm. Scale bar in inset, 2 µm.",
    "ncbi_link": "vam3: 856596"
  },
  {
    "caption": "(D) Effect of clathrin deletion on the AP-3 pathway. GFP-tagged Nyv1 with a C-terminal Snc1 transmembrane domain (GNS) was localized relative to FM4-64 stained vacuoles in the indicated strains. Labeling of the cell surface by GFP indicates a defect in the AP-3 pathway (E) Quantification of AP-3 defect from (D). Linear intensity plots were laid over the cells, the AP-3 defect was calculated by dividing GFP-intensities on the vacuolar membrane by the sum of the intensity of vacuolar, and plasma membrane signal (n ≥ 30 cells). Bars show the mean vacuolar signal over total signal ± standard deviation.",
    "ncbi_link": "clathrin: 852666"
  },
  {
    "caption": "(A-H) Indicated strains were grown in YPG for expression of Vps41-GFP-Fis constructs. Two representative images are shown for each strain. Mitochondria (M) are highlighted in red and vesicular structures in teal (unlabeled for VPS41-GFP-Fis) or green (unlabeled for VPS41-GFP-Fis). Cell wall (CW), plasma membrane (PM), and vacuoles (V) are indicated. Scale bars, 250 nm.",
    "ncbi_link": "GFP: 
Fis: 854745
VPS41: 851653"
  },
  {
    "caption": "(C) Effect of different truncations and deletions on AP-3 targeting to mitochondria. Indicated strains were grown at 30°C in YPG and kept in logarithmic phase. Localization of Apl5 or Apl6 and Vps41 was analysed by fluorescence microscopy. First column shows DIC image of cells. Scale bar, 5 µm. Scale bar in inset, 2 µm. (D) Quantification of (C). (-) Control corresponds to Vps41(ΔPEST)-GFP-Fis1 Apl6-mCherry (CUY12558) and (+) corresponds to Vps41(S-D)-GFP-Fis1 Apl6-mCherry (CUY12560). Apl5- /Apl6-dots co-localizing with GFP signal were counted and plotted in percent of the total number of Apl5- /Apl6-dots (n ≥ 63). Bars show the mean percentage of co-localization ± standard deviation.",
    "ncbi_link": "GFP: 
mCherry: 
Apl6: 853177
Fis1: 854745
Vps41: 851653"
  },
  {
    "caption": "(C) Volcano plots of proteins in close proximity to Apl5-TurboID versus control cells, from a label-free proteomics analysis of streptavidin-biotin pulldowns. The logarithmic ratios of protein intensities are plotted against negative logarithmic P values of two tailed Student's t-test, equal variance, performed from n = 3 independent experiments. The red dashed line (significance, 0.05) separates specifically identified proteins (top right portion of plot) from background. Selected top hits are indicated with black dots,",
    "ncbi_link": "TurboID: 
Apl5: 855906"
  },
  {
    "caption": "(E) Volcano plots of proteins in close proximity to Apl5-TurboID versus control cells in a GAL1pr-Vps41-GFP-Fis1 background, from a label-free proteomics analysis of streptavidin-biotin pulldowns with cells grown in YPG. The logarithmic ratios of protein intensities are plotted against negative logarithmic P values of two tailed Student's t-test, equal variance, performed from n = 3 independent experiments. The red dashed line (significance, 0.001) separates specifically identified proteins (top right portion of plot) from background. Selected top hits are indicated with black dots",
    "ncbi_link": "TurboID: 
Apl5: 855906"
  },
  {
    "caption": "(F) Co-localization of C-terminally GFP-tagged Apl5 and C-terminally mCherry-tagged Sec7 in wt and age2Δ background. Cells were grown at 30°C and kept in logarithmic phase. Scale bar, 5 µm. Scale bar in inset, 2 µm. (G) Quantification of co-localization from (F) normalized per cell. Number of co-localizing dots was determined and normalized to the number of co-localization events per cell. Bars show the mean number of co-localizing dots per cell ± standard deviation (n ≥ 60). ",
    "ncbi_link": "age2: 854767"
  },
  {
    "caption": "(A, B) AP-3 sorting defects in strains overexpressing Gcs1 (A) or Age2 (B). The AP-3 reporter GNS was localized relative to FM4-64 stained vacuoles in the indicated strains. Scale bar, 5 µm.",
    "ncbi_link": "Age2: 854767
Gcs1: 851372"
  },
  {
    "caption": "(E, F) AP-3 sorting defects in GAP-dead mutants of Gcs1 (E) and Age2 (F). The AP-3 reporter GNS was localized relative to FM4-64 stained vacuoles in the indicated strains. Scale bar, 5 µm.",
    "ncbi_link": "Age2: 854767
Gcs1: 851372"
  },
  {
    "caption": "(G) Localization of AP-3 in GAP-dead mutants of Gcs1 and Age2. Localization of C-terminally GFP-tagged Apl5 relative to FM4-64 stained vacuoles in the indicated strains. Scale bar, 5 µm. (H) Quantification of Apl5 dots in (G). Apl5-positve dots were counted and averaged to the number of dots per cell. Box boundaries indicate 25% and 75% of the dataset. The middle line indicates the median and the small square the mean. ",
    "ncbi_link": "Age2: 854767
Gcs1: 851372"
  },
  {
    "caption": "(A-C) The relative levels of (A) canalicular membrane (BA) transporter Bsep, Mrp2, Mdr1b, Mdr2, Abcg5 and Abcg8 mRNA transcripts, (B) basolateral membrane BA transporter Mrp3, Mrp4, Ostβ, Ntcp and Oatp1a1 mRNA transcripts, and (C) BA synthetic enzyme Cyp7a1, Cyp7b1, Cyp8b1, Cyp27a1, and Cyp2c70 mRNA transcripts. Wild type, wild type mice, n=6; Heterozygote, Sema7aR145W heterozygous mice, n=5; Homozygote, Sema7aR145W homozygous mice, n=7. Data are shown as means ± SD. *P < 0.05 versus the WT mice, #P < 0.05 versus the heterozygous mutant mice. The data were analyzed by the independent-samples Student's t-test and the Mann-Whitney U test.",
    "ncbi_link": "Bsep: 27413
Mdr1b: 18669
Mdr2: 18670
Mrp2: 12780
Mrp3: 76408
Mrp4: 239273
Abcg5: 27409
Abcg8: 67470
Cyp27a1: 104086
Cyp2c70: 226105
Cyp7a1: 13122
Cyp7b1: 13123
Cyp8b1: 13124
Sema7a: 20361
Ntcp: 20493
Ostβ: 330962
Oatp1a1: 28248"
  },
  {
    "caption": "(D) Western blot analysis of the relative levels of Bsep, Mrp2, Mdr2, Mrp3, Mrp4, Ostα/β, Ntcp, Cyp7a1 and Cyp8b1 protein expression in mouse livers. Contrary to the mRNA alterations, the levels of canalicular membrane Bsep and Mrp2 proteins were dramatically reduced in homozygous mouse livers, suggesting that the decreased these proteins were might be mediated by post-translational regulation in the livers of Sema7aR145W mutant mice. Wild type, wild type mice, n=4; Heterozygote, Sema7aR145W heterozygous mice, n=5; Homozygote, Sema7aR145W homozygous mice, n=5. *P < 0.05 versus the WT mice, #P < 0.05 versus the heterozygous mutant mice. The data were analyzed by the independent-samples Student's t-test and the Mann-Whitney U test.",
    "ncbi_link": "Sema7a: 20361"
  },
  {
    "caption": "(G) Multiplex IF analyses revealed that transfection with the SEMA7A_WT or SEMA7A_R148W construct decreased the levels of canalicular membrane Bsep and Mrp2 expression in mouse primary hepatocytes in collagen sandwich cultures in a dose-dependent manner (0, 0.2, 1.0 μg per well of 6-well plate; 1.5 ml culture medium per well). Scale bar, 50 µm. Together, the Sema7aR145W mutation can reduce hepatic Bsep and Mrp2 protein expression and lead to intrahepatic BA accumulation and cholestasis (Appendix Table S16). Subsequently, cholestasis triggered an adaptive response in the liver by down-regulating the expression of BA synthetic enzymes of Cyp7a1 and Cyp8b1 and up-regulating the expression of BA efflux transporters Mrp3, Mrp4 and Ostα/β.",
    "ncbi_link": "SEMA7A: 20361
Sema7a: 20361"
  },
  {
    "caption": "A Confocal microscopy images representing the localization of PCDH7. U2OS cells expressing full‐length (WT) PCDH7 at mitosis (top) and interphase (middle). Cytoplasmic deleted (CytΔ) PCDH7‐expressing cells at mitosis (middle) and interphase (bottom). PCDH7, green; DNA, blue. Scale bar, 20 μm.B Quantification of PCDH7::GFP (WT and CytΔ) protein localization on the cell surface in mitosis [WT (n = 11), CytΔ (n = 6), red] and interphase [WT (n = 25), CytΔ (n = 20), blue]. Interphase cytΔ PCDH7 localizes to the cell surface more than WT (full length) PCDH7 (insets). Bars show mean ± SEM.",
    "ncbi_link": "PCDH7: 5099"
  },
  {
    "caption": "A PCDH7 antibody detects a single band of ˜110 kDa in luciferase RNAi (luc), PCDH1 RNAi HeLa cell lysates, but this band is not detectable in PCDH7 and PCDH1 and PCDH7 RNAi cells. α‐tubulin was used as a loading control (left). HeLa Kyoto cells stably expressing PCDH7‐LAP‐tagged BAC transgenes treated with luciferase RNAi (control) and 150 nM (1×) and 300 nM (2×) PCDH1 esiRNA and blotted against anti‐GFP, anti‐PCDH1, and anti‐actin antibodies. PCDH1 bands were reduced in PCDH1 RNAi cells, whereas mouse GFP::PCDH1 was not affected by the esiRNA treatment (right).",
    "ncbi_link": "luciferase: 
PCDH1: 75599
PCDH1: 5097
PCDH7: 5099"
  },
  {
    "caption": "B Rounding pressure plots of MYH9 (positive control, n = 7), luc (negative control, n = 12), PCDH7 (n = 11), PCDH1 (n = 12), and PCDH1 and PCDH7 (n = 11) RNAi cells. Bars show mean ± SEM (left). Rounding pressure plots HeLa Kyoto cells stably expressing PCDH7‐LAP‐tagged BAC transgenes treated with MYH9 (positive control, n = 7), luc (negative control, n = 14), PCDH1 (n = 13) esiRNA. *P 0.05; **P 0.01; ***P 0.001; ns, P > 0.05 (non‐significant).",
    "ncbi_link": "luc: 
MYH9: 4627
PCDH1: 75599
PCDH1: 5097
PCDH7: 5099"
  },
  {
    "caption": "(B) Cells expressing fluorescently-tagged α2-tubulin (atb2) were imaged every 5 seconds and the dwell time of ~100 individual iMTs recorded within the final 1.1 µm of the cell for each strain. Red bars signify the mean",
    "ncbi_link": "atb2: 2540936
α2-tubulin: 2540936"
  },
  {
    "caption": "(C) Kymographs showing fluorescently-tagged Klp5/Klp6 (Kinesin) co-imaged with fluorescently-tagged microtubules (MT) in the presence (top panels) and absence (bottom panels) of Mcp1. Banding on MT, caused by unequal incorporation of fluorescence, illustrates the force exerted on the MT by continued growth into the cell cortex. Dashed yellow line indicates the cell end",
    "ncbi_link": "Mcp1: 2542755"
  },
  {
    "caption": "(D) MT growth speed was calculated from kymographs from control (n=16) and ∆mcp1 cells (n=11), Klp5/Klp6 walk speed was calculated from multiple individual runs on the MT lattice in control (n=44) and ∆mcp1 cells (n=32)",
    "ncbi_link": "mcp1: 2542755"
  },
  {
    "caption": "(E) Average intensity of Klp5/Klp6 at the plus ends of iMTs from multiple kymographs of control (n=19) or ∆mcp1 cells (n=14)",
    "ncbi_link": "mcp1: 2542755"
  },
  {
    "caption": "(F) Mixing experiment to compare fluorescently-tagged Klp5/Klp6 levels between cells either expressing (blue, closed arrowheads) or deleted (red, open arrowhead) for Mcp1 distinguished by the absence of fluorescently-tagged nuclear envelope protein Cut11 (left panel). Scale bar, 5µm. Box plot (right panel) shows quantitated fluorescence values for nuclear levels of Klp5/Klp6 in control (n=44) and ∆mcp1 cells (n=45) and at the MT plus end in control (n=64) and ∆mcp1  cells (n=35) prior to shrinkage",
    "ncbi_link": "mcp1: 2542755
Mcp1: 2542755"
  },
  {
    "caption": "(B) Kymographs showing fluorescently-tagged MTs co-imaged with fluorescently-tagged Tea2 kinesin in control cells (top panels) or in the absence of Klp6 (middle panels) or Mcp1 (bottom panels). Dashed yellow line indicates the cell end",
    "ncbi_link": "Klp6: 2539700
Mcp1: 2542755"
  },
  {
    "caption": " (C) Intensity of Tea2 at plus ends quantitated from multiple kymographs of the type in (B) for control (n=16), ∆klp6 (n=13) or ∆mcp1 (n=14) cells ",
    "ncbi_link": "klp6: 2539700
mcp1: 2542755"
  },
  {
    "caption": "(D) Kymographs showing fluorescently-tagged MTs co-imaged with fluorescently-tagged Klp5/Klp6 in control (top panels, repeated from 1C) or ∆tea2 cells (bottom panels). Dashed yellow line indicates the cell end",
    "ncbi_link": "tea2: 2539857"
  },
  {
    "caption": "(b) Total RNA sequencing of cenRNAs in yeasts. Left; read counts per million tracks for CEN16 in wildtype (black, top) and DAD1E50D humanized (red, bottom) yeasts. Right; heatmap of cenRNAs transcripts per million counts across all chromosomes in wildtype and DAD1E50D humanized strains. Centromere VI is marked with an asterisk to indicate that the plasmid encoding the histone plasmid also encodes a CEN6 sequence, which reads likely emanant",
    "ncbi_link": "histone: 
DAD1: 851579"
  },
  {
    "caption": "(c) RT-PCRs of the indicated RNAs. Lane 1 is genomic DNA, lane 2 is wildtype shuffle strain (yDT67), lane 3 is BY4742, lane 4 is DAD1E50D humanized, lane 5 is scc4D65Y humanized, lanes 6-9 are the same as 2-5, but without reverse transcriptase added, lane 10 is no DNA.",
    "ncbi_link": "DAD1: 851579
scc4: 856890"
  },
  {
    "caption": "(e) DASH mutants increase histone-humanization in the scc4D65Y background. Humanization rates of the scc4D65Y mutant with and without DAD1E50D or DAM1N80Y. Significance of the mean difference in 5-FOAR frequency was determined with the Mann-Whitney test. Each dot represents one biological replicate (n = 8), central band represents the median, box extends from the 25th to 75th percentiles, and whiskers represent the minimum and maximum.",
    "ncbi_link": "DAD1: 851579
DAM1: 853010
scc4: 856890"
  },
  {
    "caption": "(f) Ploidy analysis by flow cytometry in the scc4D65Y humanized mutants from panel d. Flow cytometry data from humanized lineages yHs5 and yHs7 are shown for aneuploid and euploid controls, respectively.",
    "ncbi_link": "scc4: 856890"
  },
  {
    "caption": "(a) Growth assays of wild type, ipl1-2 mutants, and ipl1-2 kinetochore double mutants at permissive (24ºC) and non-permissive temperature (32ºC). Ten-fold serial dilutions of ~1.0 OD600 yeast cultures were spotted onto YPD solid media and grown at the indicated temperatures for four and three days, respectively.",
    "ncbi_link": "ipl1: 855892"
  },
  {
    "caption": "(b) Flow cytometry analysis of wild type, ipl1-2 mutants, and ipl1-2 kinetochore double mutants at the permissive (24˚C) and non-permissive temperature (30ºC). Yeast cultures were grown to logarithmic phase at 24˚C and divided and grown at 24˚C and 30˚C for 6 hours before cells were collected and processed for DNA content analysis using Sytox Green stain.",
    "ncbi_link": "ipl1: 855892"
  },
  {
    "caption": "(c) Growth assays of wild type, mad3∆ mutants, and mad3∆ DAD1E50D double mutants on YPD with and without 30 µg/ml benomyl. Ten-fold serial dilutions of ~1.0 OD600 yeast cultures were spotted onto the indicated solid media and grown at 30˚C for three days.",
    "ncbi_link": "DAD1: 851579
mad3: 853439"
  },
  {
    "caption": "(b) Histone-humanization assay for various dam1N80X mutants. 5-FOA is used to counter-select the yeast histone plasmid, forcing growth with the human histone plasmid. Yeast were serially diluted from a starting culture of 1.0 OD600.",
    "ncbi_link": "dam1: 853010
histone: 126961///8358///391769///440093///340096///8350///8968
histone: 851811///855976///852284///854150///851810///855701///852294///855700///852295///852283"
  },
  {
    "caption": "(a) Sporulation efficiency after five days in sporulation medium at 25 ˚C. Example micrographs are shown to the left for both wildtype and DAD1E50D SK1 strains. Right, quantification of average sporulation efficiency from all micrographs. Two tailed unpaired t test of the mean difference in sporulation efficiency. Each dot represents the fraction of cells sporulated in a single field of view (technical replicates; n ≥15), central band represents the median, box extends from the 25th to 75th percentiles, and whiskers represent the minimum and maximum.",
    "ncbi_link": "DAD1: 851579"
  },
  {
    "caption": "(b) Spore viability assay. Individual tetrads were micromanipulated on a agar surface and spores were dissected and arrayed. Genotype was determined by PCR genotyping of the DAD1 locus. Quantification from all tetrad dissections performed, total are shown below. The one-tailed probability of observing 51% spore viability in DAD1E50D SK1 over a total of 139 tetrads is p < 0.000001, assuming a spore viability of ~90% from wild type SK1.",
    "ncbi_link": "DAD1: 851579"
  },
  {
    "caption": "RT-qPCR assay on nuclear  RNA for assessing the uncleaved/total ratio of p53  and TATA-binding protein (TBP) pre-mRNAs in A549  cells (n=3) transfected for 48 hours with two different siRNA targeting PCF11  prior to exposure (UV+) or not (UV-) to  UV irradiation  (40 J/m2). \"n\" indicates the number of biological replicates for each experiment. All data are presented as the mean ± s.e.m. P values were calculated using two-sided unpaired t-test.",
    "ncbi_link": "PCF11: 51585
TATA-binding protein: 6908
TBP: 6908
p53: 7157"
  },
  {
    "caption": "RT-qPCR  analysis on RNA extracted from nucleoplasm  and chromatin  fractions. The ratio of uncleaved pre-mRNA (nucleoplasm/chromatin) was calculated to quantify the level of unprocessed p53, TBP, WDR13  and GAPDH  pre-mRNA (n=3 biological replicates) released in the nucleoplasm  compared to the chromatin-bound unprocessed pre-mRNA. WDR13  and GAPDH  were included as controls as they have been previously reported to be processed post- and co-transcriptionally, respectively. Data are presented as the mean ± s.e.m.",
    "ncbi_link": "GAPDH: 2597
TBP: 6908
p53: 7157
WDR13: 64743"
  },
  {
    "caption": "RT-PCR  analysis of p53  3' flanking region using the same primers employed in the data panel above (n=3). Lane 1 is a control PCR  amplification of cDNA derived from the reverse transcription  of a control mRNA using  oligo (dT). Lanes 2-7 are PCR  amplification of reverse transcribed p53 chromatin-associated pre-mRNA using oligo oligo (dT).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "RT-qPCR  assay on nuclear  RNA for assessing the uncleaved/total ratio of p53  pre-mRNA in wild type (WT) and CoTC  deleted (ΔCoTC) A549  cells (n=3) treated with or without UV irradiation (40 J/m2). \"n\" indicates the number of biological replicates for each experiment. All data are presented as the mean ± s.e.m. P values were calculated using two-sided unpaired t-test.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "RT-qPCR measuring relative p53  and p21  mRNA levels in wild type (WT) and CoTC-deleted (ΔCoTC) cells (n=3) in response to UV  treatment (40 J/m2). The expression was normalized to HPRT. \"n\" indicates the number of biological replicates for each experiment. All data are presented as the mean ± s.e.m. P values were calculated using two-sided unpaired t-test.",
    "ncbi_link": "p21: 1026
HPRT: 3251
p53: 7157"
  },
  {
    "caption": "Real-time qPCR analysis of fetal organoids cultured for one month showing decrease in relative expression of indicated neonatal markers A Ass1, B Blimp-1, C FcRn and D Lct and increase of the adult markers E Sis, F Treh and G Arg2 (n=3 individual wells from single organoid culture (see material and methods); experiment was repeated in four to eight independent organoid cultures with similar results).",
    "ncbi_link": "Arg2: 11847
Ass1: 11898
FcRn: 14132
Lct: 226413
Blimp-1: 12142
Sis: 69983
Treh: 58866"
  },
  {
    "caption": "Relative expression detected by Real-time qPCR in fetal organoids ( ) and adult organoids ( ). Neonatal markers A Ass1, B Blimp-1, C FcRn and D Lct in fetal organoids cultured for one month compare to levels adult organoids. Mature markers E Sis, F Treh and G Arg2 increase in fetal organoids to adult levels (n=3 individual wells from single organoid culture (see material and methods); experiment was repeated in four independent organoid cultures with similar results).",
    "ncbi_link": "Arg2: 11847
Ass1: 11898
FcRn: 14132
Lct: 226413
Blimp-1: 12142
Sis: 69983
Treh: 58866"
  },
  {
    "caption": "Maturation is accelerated in dexamethasone treated fetal organoids ( ) compared to control ( ), as revealed by real-time qPCR. Decrease in relative expression of neonatal marker A Blimp-1 and increase in expression of adult marker B Sis occur earlier in dexamethasone treated organoids",
    "ncbi_link": "Blimp-1: 12142
Sis: 69983"
  },
  {
    "caption": "Maturation is accelerated in dexamethasone treated fetal organoids ( ) compared to control ( ), as revealed by real-time qPCR. expression of adult marker E Treh and F Arg2 remains unchanged (n=3 individual wells from single organoid culture",
    "ncbi_link": "Arg2: 11847
Treh: 58866"
  },
  {
    "caption": "(F) Representative ET reconstructions of mitochondria from a WT cell (left), a Mic10-KO cell (center) and a Mic60-KO cell (right). The OM is displayed in clear grey, the side of the IM that faces the matrix is shown in dark blue. The IM side that faces the IMS is shown in light blue.",
    "ncbi_link": "Mic60: 10989
Mic10: 440574"
  },
  {
    "caption": "(A Nanoscopy of mitochondria of WT and Mic10-KO cells, as indicated. (A) Mitochondria were immunolabeled for Mic60 and ATPB and visualized by 2D STED nanoscopy.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(C) 3D MINFLUX nanoscopy. Mic10-KO cells were immunolabeled for Mic60 using a directly labeled antibody. Colors encode depth information.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(D) 3D SIM of living WT and Mic10-KO cells. Cells were labeled with Mitotracker Green. Images show maximum intensity projections.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(E) FIB-SEM of Mic10-KO cells. Shown is a representative reconstructed mitochondrion. Dashed box: Orthoslice view on the smaller mitochondrion. The OM and IBM are displayed together in clear grey, the CM in is shown in blue.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(F) 2D STED nanoscopy of mitochondria. Mic19-KO cells were transfected with a plasmid for Mic10-FLAG expression under the control of a tetracycline-inducible promoter. Left panel: Mitochondria from noninduced cell. Right: Mitochondria from induced cell expressing Mic10-FLAG.",
    "ncbi_link": "FLAG: 
Mic19: 54927
Mic10: 440574"
  },
  {
    "caption": "(A) Cells were immunolabeled for Mic60 and DNA and visualized by confocal fluorescence microscopy before and after induction of Mic60 expression for 48 h.",
    "ncbi_link": "Mic60: 10989"
  },
  {
    "caption": "(B) Protein levels of MICOS proteins after Mic60 induction. Cell lysates were analyzed by western blotting at the indicated time points.",
    "ncbi_link": "Mic60: 10989"
  },
  {
    "caption": "(C) Recovery of mitochondrial networks upon Mic60 re-expression. Cells were induced with doxycycline hyclate for 72 h, immunolabeled for TOM20 and visualized by confocal microscopy.",
    "ncbi_link": "Mic60: 10989"
  },
  {
    "caption": "(D-G) TEM of Mic60-TO cells before and after induction. (D) TEM recordings of Mic60-TO cells at the indicated time points. (E) Quantification of the cristae morphology. (F) CJ frequency. The number of CJs on TEM recordings was normalized to the length of the OM. At least 90 mitochondrial sections were analyzed for each sample. (G) Quantification of the cristae morphology of Mic60-TO cells. Only mitochondria exhibiting at least one CJ were analyzed. Data information: n: Number of mitochondrial sections. Scale bars: 20 µm (A), 10 µm (C), 500 nm (D).",
    "ncbi_link": "Mic60: 10989"
  },
  {
    "caption": "(A,B) Live-cell nanoscopy of Mic10-TO cells. Cells expressing COX8A-SNAP were labeled with SNAP-cell SiR and recorded with STED nanoscopy. (A) Cristae architecture in noninduced cells. (B) Cristae architecture after Mic10 re-expression (24 h induction with doxycycline). STED image data were deconvolved.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(C) STED nanoscopy of fixed Mic10-TO cells. Cells were induced for 24 h and immunolabeled for Mic60 and Mic10-FLAG. Upper row: Cell with weak Mic10 expression level. Lower row: Cell with strong Mic10 expression level.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(D-G) TEM of Mic10-TO cells. (D) Cells induced for the indicated period of time were recorded with TEM. Arrow indicates an intermediately shaped crista. (E) Quantification of the cristae morphology. n: Number of mitochondrial sections. (F) CJ frequency in Mic10-TO cells. Number of CJs was normalized to the length of the OM. The same sections were analyzed as in (E). (G) Diameter of CJs estimated on TEM recordings. Data information: n: Number of analyzed mitochondrial sections (E) or CJs (G).. ",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(A) FIB-SEM of Mic10-TO cells. Cells were induced for 0 h, 16 h and 24 h. The representative reconstructions show mitochondria from noninduced, rescued and intermediate cells, as indicated. The OM is shown together with the IBM in clear grey, the CM in blue.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "(B) ET of Mic10-TO cells. Mic10 expression was induced for 0 h and 16 h. Shown are reconstructions of representative noninduced and almost completely rescued mitochondria. The OM is displayed in clear grey, the side of the IM that faces the matrix is shown in dark blue. The IM side that faces the IMS is shown in light blue.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "Knockdown (KD) of OPA1 in HeLa cells. WT and Mic60-KO cells were transfected with a scrambled control (Ctrl.) or siRNA pools against OPA1 (OPA1-KD) for 5 d. (A) Cell lysates were analyzed by western blotting. ",
    "ncbi_link": "Mic60: 10989
OPA1: 4976"
  },
  {
    "caption": "(B) TEM recordings from OPA1 depleted WT and Mic60-KO cells. Arrows point to a septum.",
    "ncbi_link": "Mic60: 10989
OPA1: 4976"
  },
  {
    "caption": "(C,D) Quantification of the cristae morphology of OPA1 deficient WT (C) and Mic60-KO (D) cells. The number of CJs was normalized to the length of the OM (C). The number of septated mitochondria in Mic60-KO cells was estimated (D).",
    "ncbi_link": "Mic60: 10989
OPA1: 4976"
  },
  {
    "caption": "(E,F) ET of mitochondria from OPA1-KD cells. WT cells were transfected with a scrambled control (E) or siRNA pools against OPA1 (F) for 48 h. Reconstructions of representative mitochondria are displayed. The OM is displayed in clear grey, the side of the IM that faces the matrix is shown in dark blue. The IM side that faces the IMS is shown in light blue.",
    "ncbi_link": "OPA1: 4976"
  },
  {
    "caption": "WT and Mic10-KO cells were transfected with a scrambled control (Ctrl.) or siRNA pools against OPA1 (OPA1-KD) for 72 h. (A,B) STED nanoscopy of OPA1 depleted WT (A) and Mic10-KO (B) cells. Cells were immunolabeled for Mic60 and ATPB.",
    "ncbi_link": "Mic10: 440574
OPA1: 4976"
  },
  {
    "caption": "(C) TEM of OPA1 depleted Mic10-KO cells. Left: Representative TEM recordings showing CJs marked by arrows in a control cell and a similar view for an OPA1-KD cell. The CMs are colored in green and the OM and IBM together in magenta. Right: Quantification of mitochondria containing CJs or septa junctions. Sections that contained CJ-like structures were analyzed. Of these, the number of sections exhibiting septa or cristae structures (other) was quantified.",
    "ncbi_link": "Mic10: 440574
OPA1: 4976"
  },
  {
    "caption": "(D Depletion of ATP5ME in HeLa cells. Cells were transfected with a scrambled control or siRNA pools against ATP5ME for 4 d. TEM recording (left) and quantification of the number of cristae per mitochondrial section (right).",
    "ncbi_link": "ATP5ME: 521"
  },
  {
    "caption": "(E) Cells depleted of ATP5ME were immunolabeled for Mic60 and recorded with STED. The arrows point to crossing points of the opposite Mic60 distribution bands.",
    "ncbi_link": "ATP5ME: 521"
  },
  {
    "caption": "(E and F) RT-PCR and western blot showing the effect of RNAi-mediated B52 depletion in S2R+ cells (E) and in larval wing discs (F).",
    "ncbi_link": "B52: 41670"
  },
  {
    "caption": "(D) Quantification of Posterior/Total wing area in male flies of the genotypes illustrated in panel C. UAS-GFP was used as a control. Each point represents a single wing, bars represent mean with standard deviation. *** p-value<0.001, **** p-value<0.0001 (unpaired two-tailed t-tests). Flies were grown at 18°C.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(C) Quantification of Yki reporter genes expression upon overexpression of Yki isoforms in the wing posterior domain (hh-Gal4 driver). For each target gene, relative expression between posterior and anterior domain in the wing discs was quantified by immunostaining using anti-ßgal antibody (for ex-lacZ and diap1-lacZ) or direct visualization of GFP (ban-sensor, in this case posterior domain was visualized by immunostaining against V5-tag present in UAS-Yki transgenes). In the scatter dot plot, each symbol (circle, square and triangle) represents a single wing disc, bars represent mean with SEM. ** p-value<0.01; **** p-value<0.0001 (unpaired two-tailed t-tests).",
    "ncbi_link": "lacZ: 
diap1: 39753
ex: 33218
Gal4: 855828
ban: 12798547
Yki: 37851"
  },
  {
    "caption": "(G) Luciferase assay using 3xSd-Luciferase reporter in S2 cells, transfected with single or combination of Yki isoforms. Error bars represent SD, n=6. * p-value<0.05; **** p-value<0.0001 (unpaired two-tailed t-tests).",
    "ncbi_link": "Luciferase: 
Sd: 32536
Yki: 37851"
  },
  {
    "caption": "(H) Co-overexpression of Yki isoforms using GMR-Gal4 driver provides evidence of competition between Yki isoforms.",
    "ncbi_link": "Gal4: 855828
Yki: 37851"
  },
  {
    "caption": "(C) Comparison of posterior/total area ratio of females wings upon depletion of B52 in a yki+ (wild type) or yki2-only background. Each point corresponds to a single wing, bars represent mean with SD (unpaired two-tailed t-tests: **** p-value <0.0001).",
    "ncbi_link": "B52: 41670
yki: 37851"
  },
  {
    "caption": "(E and F) Quantification of sibling clones size in the wing pouch. In (D), sibling wild-type clones are labelled with 2xGFP and 2xRFP. In (E), unlabelled clones are homozygous for the yki2-only-A allele whereas sibling clones (RFP/RFP) are wild type. In both graphs, clones pairs are sorted according to RFP/RFP clones size.",
    "ncbi_link": "GFP: 
RFP: 
yki: 37851"
  },
  {
    "caption": "(A-C) Atg7+/+ and Atg7-/- MEFs stably expressing GFP‐Gal3 (A, C) or GFP‐Ub (B) were treated with 1000 μM LLOMe or 250 μg/ml silica for 3 h. Cells were subjected to immunocytochemistry using the following antibodies: anti‐LC3 and anti‐Lamp1 (A), anti‐p62 and anti‐Lamp1 (B), or anti‐FK2 and anti‐p62 (C). Bars: 10 μm.",
    "ncbi_link": "Atg7: 74244
Gal3: 16854
Ub: 78294///22186///22190///22187"
  },
  {
    "caption": "(A, B) NIH3T3 cells stably expressing GFP‐Gal3 and either empty vector (control) or mStrawberry‐Atg4BC74A (Atg4B mutant) were treated with 1000 μM LLOMe for 1 h. After LLOMe washout, cells were fixed at the indicated time points and subjected to immunocytochemistry for Lamp1 and DAPI (blue) (A). The number of GFP‐Gal3 or Lamp1 puncta per cell was quantified using G‐Count (see also Supplementary Figure S4A and B). Then, the percent of GFP‐Gal3‐positive Lamp1 puncta was determined (B). The data represent means±s.d. At least 70 cells were counted (n=3). Bars: 20 μm.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Atg4B: 66615
Gal3: 16854"
  },
  {
    "caption": "(C-E) HeLa cells transfected with tfGal3 and either One‐STrEP‐FLAG‐tagged Atg4BC74A (Atg4B mutant) or empty vector (control) were observed by confocal microscopy after treatment as shown in Figure 2A and B. The number of GFP±RFP+ or GFP+RFP+ puncta per cell was quantified using G‐Count (D). Then, the percent of GFP+RFP+tfGal3 puncta was calculated (E). The data represent means±s.d. At least 30 cells were counted (n=3). Bar: 10 μm.",
    "ncbi_link": "Atg4B: 23192
Gal3: 16854"
  },
  {
    "caption": "(F-H) NIH3T3 cells stably expressing empty vector (control) or mStrawberry‐Atg4BC74A (Atg4B mutant) were treated with 1000 μM LLOMe for 1 h. After LLOMe washout, cells were cultured in the presence or absence of both 10 μg/ml E64d and Pepstatin A, fixed at the indicated time points, and subjected to immunocytochemistry for Gal3 (green) and DAPI (blue) (F). The number of endogenous Gal3 puncta per control (G) or Atg4B‐mutant (H) cells was quantified by G‐Count. The data represent means±s.d. At least 50 cells were counted (n=3). Bars: 20 μm.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "(A-F) HeLa cells stably expressing GFP‐LC3 were transfected with mStrawberry‐Gal3, and treated with 1000 μM LLOMe for 1 h. Then, cells were fixed and observed by confocal microscopy (A). The same specimens were further examined by transmission electron microscopy (B-F). Green: LC3; magenta: Gal3; blue: DAPI.",
    "ncbi_link": "Gal3: 3958
LC3: 440738///81631///84557"
  },
  {
    "caption": "(G-I) NIH3T3 cells stably expressing CFP‐Gal3 and YFP‐LC3, and either empty vector (control) (G, H) or mStrawberry‐Atg4BC74A (I) were treated with 1000 μM LLOMe for 2 h, fixed, and observed by confocal microscopy. The electron micrographs were taken in the same sample field as the transmission electron microscope. Green: LC3; blue: Gal3 and DAPI; black arrow: single membrane; white arrow: autophagosome; white arrowhead: ER membrane.",
    "ncbi_link": "Atg4B: 66615
Gal3: 16854
LC3: 67443///66734"
  },
  {
    "caption": "(A) Plasmacreatinine and ureanitrogen in Atg5F/F and Atg5F/F;KAPmice treated with vehicle or UA+OA. The values displayed represent means±s.e. Statistically significant differences (*P0.05) are indicated. F/F: Atg5F/Fmice; F/F;KAP: Atg5F/F;KAPmice.",
    "ncbi_link": "Atg5: 11793
KAP: 16483"
  },
  {
    "caption": "(B, C) PAS‐stained renal cortical region of Atg5F/F and Atg5F/F;KAP mice treated with vehicle or UA+OA (n=4-7). Bars: 40 μm (B). Kidney injury score of Atg5F/F and Atg5F/F;KAP mice treated with vehicle or UA+OA (C).",
    "ncbi_link": "Atg5: 11793
KAP: 16483"
  },
  {
    "caption": "(D) Kidney cortexes from Atg5F/F and Atg5F/F;KAP mice treated with vehicle or UA+OA were subjected to immunohistocheminal analysis of Lamp1 and LC3. Green: LC3; magenta: Lamp1; blue: DAPI. F/F: Atg5F/F mice; F/F;KAP: Atg5F/F;KAP mice. Bar: 5 μm.",
    "ncbi_link": "Atg5: 11793
KAP: 16483"
  },
  {
    "caption": "(E) Electron micrographs of kidney proximal tubules in Atg5 F/F and Atg5F/F;KAP mice treated with UA+OA. Yellow arrowhead: autophagosome; asterisk: lysosome; Mt: mitochondrion. Bar: 1 μm.",
    "ncbi_link": "Atg5: 11793
KAP: 16483"
  },
  {
    "caption": "C. Confocal images of U20S cells transfected with GFP tagged UTRN-mini and mCherry UTRN-ABD, stained with SIR-Actin shows F-actin structures, mainly stress fibers. Scale bar = 5µm.",
    "ncbi_link": "GFP: 
mCherry: 
UTRN: 7402"
  },
  {
    "caption": "(G) Reduced NMDA/AMPA ratio at SC-CA1 synapses of PtenΔC/ΔC mice (P17-21). The NMDAR component was obtained 60 ms after stimulation. (ratio, n = 11 cells from 8 mice for WT and 8 (8) for ΔC; decay, n = 12 cells from 8 mice for WT and 11 (8) for ΔC, **P < 0.01, ns, not significant, Mann-Whitney U test). The error bars represent SEM. (H) Reduced amplitude but not frequency of NMDA -mEPSCs at PtenΔC/ΔC CA1 pyramidal neurons. (n = 17 cells from 4 mice for WT and 18 (4) for ΔC, **P < 0.01, ns, not significant, Mann-Whitney U test, Student's t-test). The error bars represent SEM. (I) Reduced NMDA/AMPA ratio at synapses in layer II/III pyramidal neurons in the prelimbic region of the mPFC of PtenΔC/ΔC mice (P20-21). The NMDAR component was obtained 60 ms after stimulation. (n = 9 cells from 3 mice for WT and 10 (3) for ΔC, *P < 0.05, **P < 0.01, Student's t-test, Mann-Whitney U test). The error bars represent SEM. Data information: (C-F) Results from the last 10-minute recordings are shown in scatter plots. ",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "A) A volcano plot showing DEGs (adjusted p value < 0.1) derived from RNA-Seq results for PtenΔC/ΔC and WT mice (P21). For the calculation of adjusted p value, we have employed the R package DESeq2 where the P‐values obtained by the Wald test are corrected for multiple testing using the Benjamini and Hochberg method. (n = 3 mice for WT and ΔC). See also Dataset EV1 for the full RNA-Seq results.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "C) Immunoblot validation of the increase in SLC6A20 protein levels in hippocampal lysates of PtenΔC/ΔC mice (P21). We denoted the antibody as 'SLC6A20' here, not 'SLC6A20A', because this antibody was generated using a synthetic peptide sequence (YNEPSNNCQKHAI) that is commonly present in SLC6A20A and SLC6A20B, being a pan-SLC6A20 antibody (ThermoFisher). (n = 3 mice for WT and ∆C, *P < 0.05, Student's t-test). The error bars represent SEM.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(D,E) Increased phosphorylation of β-catenin at Ser-675 but not at Ser-552 in the nucleus-enriched P1 fraction but not in whole-brain lysates of PtenΔC/ΔC mice (3 months). Note that total levels of β-catenin were not changed in the P1 fraction or whole-brain lysates. (n = 4 mice for WT-WB/P1 and ΔC-WB/P1, *P < 0.05, ns, not significant, Student's t-test). The error bars represent SEM.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(B,C) Decreased extracellular levels of proline and glycine in the brains of PtenΔC/ΔC mice (2-4 month), as determined by microdialysis in the hippocampus (see Materials and Methods for details). (proline, n = 13 mice for WT and 8 for ΔC, **P < 0.01, Student's t-test; glycine, n = 9 for WT and 5 for ∆C, **P < 0.01, Student's t-test, Mann-Whitney U test). The error bars represent SEM.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(B) Normalization of NMDAR-dependent HFS-LTP at synapses of PtenΔC/ΔC mice (4-5 weeks) by DCS treatment (20 μM), as shown by fEPSP slopes. (n = 15 slices from 9 mice for WT-V/vehicle, 11 (5) for WT-D/DCS, 16 (10) for ΔC-V, 13 (7) for ΔC-D, **P < 0.01, ns, not significant, two-way ANOVA with Tukey's test). The grey traces represent the baseline fEPSP prior to LTP induction. The error bars represent SEM.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(F) Normalization of NMDAR-dependent HFS-LTP at synapses of PtenΔC/ΔC mice (4-5 weeks) by sarcosine treatment (750 µM), as shown by fEPSP slopes. Note that the data for WT-V and ΔC-V are identical to those shown in Fig. 4B because the whole experiments were performed together; we generated independent figures for DCS and sarcosine results for the clear presentation of the data. (n = 15 slices from 9 mice for WT-V/vehicle, 9 (4) for WT-Sarc/Sarcosine, 16 (10) for ΔC-V/Vehicle, 18 (4) for ΔC-S, *P < 0.05, ***P < 0.001, ns, not significant, two-way ANOVA with Tukey's test). The grey traces represent the baseline fEPSP prior to LTP induction. The error bars represent SEM.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(D) PtenΔC/ΔC mice (2-4 months) treated with Slc6a20a-ASO display partially normalized levels of whole-brain glycine, as shown by the lack of difference between saline-treated WT and ASO-treated PtenΔC/ΔC mice. Note that the glycine levels observed here are ~4 times lower than those measured in Fig. 3A, which could be attributable to different mouse ages (P21 in Fig. 3A vs. 2-4 months in Fig. 5D), absence and presence of ASO injection, or lot-to-lot variation of the ELISA kits. (n = 8 mice for WT-saline, 5 for WT-ASO, 7 for ΔC-saline, and 8 for ΔC-ASO, **P < 0.01, ns, not significant, two-way ANOVA with Tukey's test). The error bars represent SEM.",
    "ncbi_link": "Pten: 19211
Slc6a20a: 102680"
  },
  {
    "caption": "(E) PtenΔC/ΔC mice (P20-37) treated with Slc6a20a-ASO display an NMDA/AMPA ratio at hippocampal SC-CA1 synapses that is comparable to that in ASO-treated WT mice. (n = 11 neurons from 5 mice for WT-ASO, 10 (4) for ΔC-ASO, ns, not significant, Mann-Whitney's U test). The error bars represent SEM.",
    "ncbi_link": "Pten: 19211
Slc6a20a: 102680"
  },
  {
    "caption": "(G) PtenΔC/ΔC mice (2-4 months) treated with Slc6a20a-ASO display normal levels of climbing in the Laboras test. n = 6 mice for WT-saline, 7 for WT-ASO, 7 for ΔC-saline, and 8 for ΔC-ASO, *P < 0.05, **P <0.01, ns, not significant, two-way ANOVA with Bonferroni's test. The error bars represent SEM.",
    "ncbi_link": "Pten: 19211
Slc6a20a: 102680"
  },
  {
    "caption": "(D) Increased extracellular levels of glycine and proline in the brain of Slc6a20a+/- and Slc6a20a-/- mice, as shown by microdialysis analyses. Note that glycine levels are increased in both Slc6a20a+/- and Slc6a20a-/- mice, whereas proline levels are increased only in Slc6a20a-/- mice. (glycine, n = 19 mice for WT, 11 for HT, 8 for KO, **P < 0.01, Mann-Whitney U test; proline, n = 15 mice for WT, 11 for HT, 14 for KO, ***P < 0.001, ns, not significant, Mann-Whitney U test). The error bars represent SEM.",
    "ncbi_link": "Slc6a20a: 102680"
  },
  {
    "caption": "(A)The mRNA levels of QKI relative to those of 36B4 in BAT and ingWAT from HFD mice (n = 8) and lean controls (n = 8).",
    "ncbi_link": "36B4: 
QKI: 19317"
  },
  {
    "caption": "WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed a NCD or HFD for 20 weeks. The arrow indicates the time when the high fat diet（HFD）starts, and body weight was monitored weekly. (n = 10, per genotype)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Representative pictures of adipocyte-specific QKI-deficient mice under NCD or HFD conditions.",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "Gross appearance of tissues from BAT, eWAT and ingWAT fat pads from WT fl/fl and QKI KO fl/fl:AP2-Cre mice after 20 weeks on the NCD or HFD.",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "H&E staining of BAT, eWAT and ingWAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed the NCD or HFD for 20 weeks. (Scale bar represents 50 μm)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "The gross appearance of BAT, eWAT and ingWAT fat pads after administration of AAV-ShQKI or AAV-NC vectors in local adipose (ingWAT and BAT).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "H&E staining of the liver, BAT and ingWAT from AAV-NC or AAV-ShQKI mice. (Scale bar represents 50 μm).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "Representative CT images of WT fl/fl and QKI KO fl/fl:AP2-Cre mice on an NCD or HFD, showing the whole-body fat composition.",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Glucose tolerance tests (GTT) and Insulin tolerance tests (ITT) were performed on WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed the NCD or HFD for 20 weeks. Blood glucose concentrations during GTT and ITT were monitored. (n= 10, per genotype)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Blood glucose and plasma insulin levels in WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed the NCD or HFD for 20 weeks. (n = 8, per genotype)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Plasma Free Fatty Acid (FFA) and Glycerol levels in WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed the NCD or HFD for 20 weeks. (n = 8, per genotype)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "H&E and Oil Red O staining, and liver triglyceride (TG) content in WT fl/fl and QKI KO fl/fl:AP2-Cre mice fed the NCD or HFD for 20 weeks. (Scale bar represents 50 μm)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Heat production rates in WT fl/fl and QKI KO fl/fl:AP2-Cre mice (n = 8, per genotype). And average light and dark heat production rates are shown on the right.",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Heatmaps of log2 (fold change QKI KO fl/fl:AP2-Cre BAT vs. WT fl/fl BAT) for genes involved in thermogenesis and oxidation. (3 samples, per group)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Photograph of WT fl/fl and QKI KO fl/fl:AP2-Cre classical BAT in 4% paraformaldehyde solution, representative transmission electron micrographs, and UCP1 staining of BAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice.",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "The average diameter of lipid droplets and the number of mitochondria per field from WT fl/fl and QKI KO fl/fl:AP2-Cre BAT. (n = 3 biological replicates)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Total oxygen consumption rates (OCR) per gram in BAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice under basal conditions were measured using a Clark electrode. (n = 3 biological replicates)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Total oxygen consumption rates (OCR) per gram in ingWAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice under basal conditions. (n = 3 biological replicates)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Representative recording of Continuous measurement of oxygen consumption rate (OCR) in isolated mitochondria from BAT of WT fl/fl and QKI KO fl/fl:AP2-Cre mice on NCD; Oxygen consumption was performed under basal conditions, following the addition of 0. 25 mg mitochondria (Mit), 5 mM substrate glycerol-3-phosphate (G3P), 2 mM GDP, and 450 mM ADP, 2 μg/ml oligomycin, and 1.5 μM FCCP. Quantification of experimental data. (n=3 biological replicates, per group)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "The protein levels of PGC1α and QKI in siRNA-mediated QKI knockdown differentiated cell, and the quantification graph was shown on the right. (n=3 biological replicates)",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "Immunostaining of PGC1α and UCP1 in NC, Si-QKI 1, and Si-QKI 2 adipocytes. (Scale bar represents 20 μm).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "The relative mRNA levels of genes related to thermogenesis in adipocytes treated with NC, QKI siRNA or both QKI and PGC1α siRNA. (n=3 biological replicates)",
    "ncbi_link": "PGC1α: 19017
QKI: 19317"
  },
  {
    "caption": "The oxygen consumption rates in adipocytes treated with NC, QKI siRNA or both QKI and PGC1α siRNA. (n=3 biological replicates)",
    "ncbi_link": "PGC1α: 19017
QKI: 19317"
  },
  {
    "caption": "Representative pictures of oil red O staining in three adipocyte types: ShScramble+ovCon cells, QKI knockdown cells (ShQKI+ovCon) and QKI knockdown with QKI-5 re-expression cells (ShQKI+ovQKI).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "The relative mRNA levels of genes associated with energy dissipation in ShScramble+ovCon, ShQKI+ovCon and ShQKI+ovQKI differentiated cells. The results represent 3 independent experiments.",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "Construction of a series of luciferase reporter vectors (PGC1α full-length 3'UTR T, A, B, C fragments and PGC1α 3'UTR QRE motif sites mutant B M1, B M2, C M1, C M2 fragments). Luciferase activity assays to examine the functional QRE motif sites in the PGC1α 3'UTR affected by QKI. (n=4 biological replicates)",
    "ncbi_link": "luciferase: 
PGC1α: 19017
QKI: 19317"
  },
  {
    "caption": "Construction of a series of luciferase reporter vectors (UCP1 full-length 3'UTR T fragment and UCP1 3'UTR QRE motif sites mutant T M1, T M2, T M3 fragments). Luciferase activity assays to examine the functional QRE motif sites in the UCP1 3'UTR affected by QKI. (n=4 biological replicates)",
    "ncbi_link": "luciferase: 
QKI: 19317
UCP1: 22227"
  },
  {
    "caption": "Based on RIP-sequencing data, the distribution of QKI-binding peaks within UCP1 and PGC1α transcript regions.",
    "ncbi_link": "PGC1α: 19017
UCP1: 22227"
  },
  {
    "caption": "RNA immunoprecipitation followed by real-time PCR. Specific primer for PGC1α 3'UTR region 1, region 2 and UCP1 3'UTR to detect these QRE motif sites region bound to endogenous QKI in brown fat tissue, and data showing the PGC1α and UCP1 transcripts abundance in QKI IP compared with IgG IP. (n=4 biological replicates)",
    "ncbi_link": "PGC1α: 19017
UCP1: 22227"
  },
  {
    "caption": "293T cells were transfected with PGC1α wild type or QRE sites mutant 3'UTR fragments. RNA immunoprecipitation (RIP) to identify these QRE motif sites region bound to endogenous QKI by using anti-QKI antibodies. The results showed that endogenous QKI interacted with full-length wild type QRE motif regions within 3'UTRs of PGC1α",
    "ncbi_link": "PGC1α: 19017"
  },
  {
    "caption": "293T cells were transfected with UCP1 wild type or QRE sites mutant 3'UTR fragments. RNA immunoprecipitation (RIP) to identify these QRE motif sites region bound to endogenous QKI by using anti-QKI antibodies. The results showed that endogenous QKI interacted with full-length wild type QRE motif regions within 3'UTRs of UCP1.",
    "ncbi_link": "UCP1: 22227"
  },
  {
    "caption": "The mRNA stability in adipocytes was measured by incubating cells with actinomycin D (5 μg/ml). Actinomycin D was added to stop transcription, and RNAs were harvested at the indicated times (x-axis) after transcription inhibition. Real-time PCR was used to determine remaining UCP1, PGC1α and Actin mRNA levels compared with the starting time. Increasing PGC1α mRNA half-life by depletion of QKI (ShScramble T1/2 = 4.73 h, ShQKI T1/2 = 8.04 h). (n=4 biological replicates)",
    "ncbi_link": "Actin: 
PGC1α: 19017
QKI: 19317
UCP1: 22227"
  },
  {
    "caption": "Real-time PCR analysis of mRNA transcript levels of the QKI targets UCP1 and PGC1α in the nuclear and cytoplasmic fractions of differentiated MEF cells transfected with ShScramble or ShQKI. Values represent the cytoplasmic-to-nuclear ratio of each transcript. Actin served as a negative control. (n=4 biological replicates)",
    "ncbi_link": "Actin: 
PGC1α: 19017
QKI: 19317
UCP1: 22227"
  },
  {
    "caption": "RNAs from isolated nuclear and cytoplasmic fractionation were harvested after RNA immunoprecipitation (RIP) of RNA-protein complexes using either anti-QKI antibody or control IgG. And RIP-RT-PCR showing the PGC1α and UCP1 transcripts majorly interacted with endogenous QKI in the nucleus. (n=3 biological replicates)",
    "ncbi_link": "PGC1α: 19017
UCP1: 22227"
  },
  {
    "caption": "Control (ShScramble) and QKI knockdown (ShQKI) adipocyte lysates were subjected to polysome profiling, and a representative polysome profile is shown. Total RNA was extracted from each fraction, and the distribution of UCP1 and PGC1α mRNA was measured via real-time PCR (K and L). The results are shown as the percentage of total mRNA (% mRNA) in polysome fractions and represent 3 independent experiments.",
    "ncbi_link": "PGC1α: 19017
QKI: 19317
UCP1: 22227"
  },
  {
    "caption": "The rectal temperature of WT fl/fl and QKI KO fl/fl:AP2-Cre mice was monitored upon acute cold exposure (4 °C). (n = 10 mice, per group)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "H&E staining and UCP1 immunostaining of sections of ingWAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice at RT (22 °C) or following 72 h of cold exposure (4 °C). (Scale bar: 50 μm).",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "The protein levels of UCP1 in ingWAT from WT fl/fl and QKI KO fl/fl:AP2-Cre mice at RT or following 72 h of cold exposure (4 °C), and quantified protein levels are shown in (D). (n=3 biological replicates, per group)",
    "ncbi_link": "Cre: 2777477
AP2: 11770
QKI: 19317"
  },
  {
    "caption": "Red Nile staining in BAT injected with Control or QKI knockdown AAV at RT (22 °C) or following 6 h and 72 h of cold exposure (4 °C).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "TG content in BAT injected with Control or QKI knockdown AAV at RT (22 °C) or following 6 h and 72 h of cold exposure (4 °C).",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "The mRNA levels of genes related to energy consumption (PGC1α, UCP1 and Dio2). (n=4 biological replicates, per group)",
    "ncbi_link": "Dio2: 13371
PGC1α: 19017
UCP1: 22227"
  },
  {
    "caption": "The relative luminescence of a QKI promoter reporter under cAMP (Forskolin and IBMX) stimulus. (n=3 biological replicates)",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "The effect of transcriptional factors on the QKI promoter, assessed by luciferase activity assays. (n=3 biological replicates)",
    "ncbi_link": "QKI: 19317"
  },
  {
    "caption": "The relative mRNA levels of genes (UCP1, PGC1α, Dio2) in differentiated MEFs transfected with ShScramble or ShQKI lentivirus, following cAMP (Forskolin and IBMX) stimulation. (n=3 biological replicates)",
    "ncbi_link": "Dio2: 13371
PGC1α: 19017
QKI: 19317
UCP1: 22227"
  },
  {
    "caption": " b Cas9-EGFP OT-I CD8+ T cells were transfected with control sgRNA (sgEGFP) or with two different sgRNA targeting Itsn2 (sgITSN2-1 or sgITSN2-2). Transfected cells were stimulated for 48 h with N4 peptide MHC tetramers (0.1 nM) in presence or absence of soluble anti-CD28 antibody or with IL-7 as control. Cell surface expression of CD69 and CD5 were analyzed by flow cytometry (Z-score normalization of the Geometric Means of fluorescence MFI per experiment) in four independent experiments. Comparison between sgEGFP and sgITSN2 conditions were performed using a paired t-test. Boxplot elements: center line corresponds to median, box limits correspond to the first and third quartiles, whiskers indicate variability from Q1-1.5. IQR to Q3+1.5 IQR. Outliers are shown as black dots.",
    "ncbi_link": "EGFP: 
Itsn2: 20403
ITSN2: 20403"
  },
  {
    "caption": " c Proliferation of OT-I Cas9-EGFP CD8+ T cells transfected with EGFP or with ITSN2 sgRNA activated for 48 h with N4 peptide MHC tetramers (0.01-0.1 nM) in the presence or absence of soluble anti-CD28 antibody or with PMA and ionomycin (PMA/Iono) or with IL-7. Data are presented as mean ± standard deviation (SD) from four proliferative measures of two independent sgEGFP and sgITSN2 transfections. Data are representative of three independent experiments. ",
    "ncbi_link": "EGFP: 
ITSN2: 20403"
  },
  {
    "caption": " a Immunoblot analysis of equal amounts of proteins from total lysates of Cas9-EGFP OT-I CD8+ T cells transfected with sgEGFP, sgITSN2-1 or sgITSN2-2 and left unstimulated (-) or stimulated for 2 or 5 min with N4 tetramers (20 nM). Upper panel: membrane probed with antibody to phosphorylated tyrosine (Anti-p-Tyr) or anti-LAT (loading control). Lower panel: membrane probed with antibodies to anti-CBL-pY774, anti-ZAP70-pY319/352, anti-AKT-pT308, anti-ERK1/2-pY204/T202 or anti-ERK1/2 (loading control). ",
    "ncbi_link": "EGFP: 
ITSN2: 20403"
  },
  {
    "caption": " b Heat map showing normalized levels (z-score) of indicated surface markers and protein phosphorylations (left margin) from Cas9-EGFP OT-I CD8+ T cells transfected with sgEGFP or sgITSN2-1 left unstimulated (-) or stimulated for 1, 3 or 10 min with N4 tetramers (1 or 10 nM) and analyzed by mass cytometry. Z-scores were calculated from hyperbolic arcsine (arcsinh) transformed intensities. ",
    "ncbi_link": "EGFP: 
ITSN2: 20403"
  },
  {
    "caption": " d Heatmap showing scaled expression levels (z-score) of indicated surface markers and protein phosphorylations (left margin) from Cas9-EGFP OT-I CD8+ T cells transfected with sgEGFP or sgITSN2-1 and stimulated for 6 h with increasing doses of N4 peptides or PMA/Ionomycin (PI) analyzed by single-cell mass cytometry (left). Z-scores were calculated from hyperbolic arcsine (arcsinh) transformed intensities. Signal difference (mean arcsinh difference) between sgEGFP and sgITSN2-1 transfected cells is depicted on the right panel. ",
    "ncbi_link": "EGFP: 
ITSN2: 20403"
  },
  {
    "caption": "(C) Genotyping analysis of wild type (Clpp+/+), heterozygous (Clpp+/-) and homozygous (Clpp-/-) Clpp knockout animals. DNA fragments corresponding to the wild type (WT-199 bp), and knockout (KO - 273 bp) Clpploci are indicated.",
    "ncbi_link": "Clpp: 53895"
  },
  {
    "caption": "(D) Analysis of Clpp transcript levels in heart (n=4). Bars represent mean ± standard deviation (SD). Student's t-test was used to determine the level of statistical difference.",
    "ncbi_link": "Clpp: 53895"
  },
  {
    "caption": "(E) Western blot analysis of CLPPprotein levels in heart (He), quadriceps (Quad), liver (Li), kidney (Ki), lung (Lu), brain (Br), spleen (Sp) and pancreas (Pa). TUBULIN and ACTIN are used as a loading control. The arrowhead indicates positions of CLPP, and the star indicates position of cross-reacting bands.",
    "ncbi_link": "CLPP: 53895"
  },
  {
    "caption": "(C) Respiratory chain enzyme activities. Relative enzyme activities of respiratory chain enzyme C I (NADH coenzyme Q reductase), C I/III (NADH cytochrome c reductase), C II (succinate dehydrogenase), C II/III (succinate cytochrome c reductase) and C IV (cytochrome c oxidase) in mitochondrial extracts from wild type and Clpp knockout hearts. (n=5). Bars present mean levels ± SD. Statistical difference was calculated by Student's t-test and changes are presented in the figure (n=5).",
    "ncbi_link": "Clpp: 53895"
  },
  {
    "caption": "(E) Decrease of steady-state levels of respiratory chain subunits in Clpp-knockout hearts relative to wild type (set to 1). VDAC or TOMM20 were used as loading controls. Bars present mean levels ± SD. Student's t-test was used to determine the level of statistical difference (n=4).",
    "ncbi_link": "Clpp: 53895"
  },
  {
    "caption": "(B-C) Northern blot analysis and corresponding quantification of mitochondrial (B) rRNAs and mRNAs or (C) tRNAs. 18S rRNA is used as loading control. Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (12S n=5 and the rest of samples n=4).",
    "ncbi_link": "18S: "
  },
  {
    "caption": "(C) Quantitative analysis of the COXI recovery upon treatment with antibiotics (Actinonin, DOXY - doxycycline and CAP - chloramphenicol) as in B. The values represent ratios of recovered (48h, - antibiotics) versus untreated (0h) COXI levels. Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (12S n=5 and the rest of samples n=4). (Actinonin and CAP n=3, DOXY n=4).",
    "ncbi_link": "12S: "
  },
  {
    "caption": "(D) Sucrose density gradient sedimentation profile of ribosomal proteins and mtRNAs from heartmitochondria. The migration of ribosomal subunits (28S and 39S) and mitoribosome (55S) was detected by immunobloting with antibodies against MRPS35 and MRPL12. The profile of a given mt-RNA is calculated after qRT-PCR analysis of individual fractions and corrected for its abundance in the cell according to results of Northern blot analysis. Results of individual experiments are provided for 12S and 16S rRNA, and for mt-mRNAs, results of distribution from two independent experiments using probes against ATP6, COXIII and ND5 were combined. Error bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (n=3).",
    "ncbi_link": "16S: 27471
ATP6: 17705
COXIII: 17710
ND5: 17721
28S: 236598
12S: 17724"
  },
  {
    "caption": "(E) Relative association of 12S rRNA, 16S rRNA and mt-mRNAs with mitoribosomes (55S) in Clpp knockout mitochondria comparing to wild type. Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (12S and 16S n=3; mRNA n=6).",
    "ncbi_link": "16S: 27471
Clpp: 53895
12S: 17724"
  },
  {
    "caption": "(B) Western blot analysis and subsequent quantification of ERAL1 and EFG1 levels from Clpp knockout (Clpp-/-) heartmitochondria relative to wild type (Clpp+/+). Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (n=4). The arrowhead indicates positions of EFG1.",
    "ncbi_link": "Clpp: 53895"
  },
  {
    "caption": "(C) Expression levels of potential CLPP substrates from Clpp knockout (Clpp-/-) heartmitochondria relative to wild type (set to 1). Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (n=4).",
    "ncbi_link": "CLPP: 53895
Clpp: 53895"
  },
  {
    "caption": "(E) Western blot analysis and subsequent quantification of protein levels in wild type (C1, C2) and Clpp knockout (KO1, KO2) MEFs upon Clpx siRNA (Clpx) relative to untreated (Ctrl) wild type. Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (n=6). The arrowhead indicates positions of either CLPX or ERAL1, and stars indicate position of cross-reacting bands.",
    "ncbi_link": "Clpp: 53895
Clpx: 270166"
  },
  {
    "caption": "(A) Sucrose density gradient sedimentation profile (\"short gradients\") of ribosomal proteins and transcripts from control (Clpp+/+) and Clpp knockout (Clpp-/-) heartmitochondria. The migration of ribosomal subunits (28S and 39S) and mitoribosome (55S) was detected by immunoblotting with antibodies against MRPS35 and MRPL12. 12S rRNA was analysed by Northern blot.",
    "ncbi_link": "Clpp: 53895
28S: 236598
12S: 17724"
  },
  {
    "caption": "(C) Relative abundance of proteins bound to the 28S ribosomal subunit (fractions 3 and up). Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (ERAL1 n=4; EFG1, CLPX, MTIF2 n=3; EFTU n=2).",
    "ncbi_link": "28S: 236598"
  },
  {
    "caption": "(D) Sucrose density gradient sedimentation profile (\"long gradients\" as in figure 4D) of ERAL1, MRPS35, MRPL37, CLPX and EFG1 from control (Clpp+/+) and Clpp knockout (Clpp-/-) heartmitochondria. The same amount of protein lysates were separated by the gradient and the amount of each individual protein is estimated after Western blot analysis (Input). Only fractions 4 - 11 containing the 28S, 39S and 55S ribosomal fractions were blotted to avoid high signals arising in free fractions (1-3).",
    "ncbi_link": "Clpp: 53895
28S: 236598"
  },
  {
    "caption": "(B) Sucrose density gradient migration profile - association of ERAL1 with the 28S ribosomal subunit (MRPS35) upon Eral1 siRNA. TOMM20 was used as a loading control.",
    "ncbi_link": "Eral1: 57837
28S: 236598"
  },
  {
    "caption": "(C) De novo synthesis of mitochondrial proteins in wild type (Clpp+/+) and Clpp knockout (Clpp-/-) MEFs upon Eral1 siRNA. Proteins were isolated after labeling with 35S-methionine for 1 hour from cells on control siRNA (Ctrl) or cells on Eral1 siRNA (Eral1). Positions of individual mitochondrial encoded proteins are indicated. Coomassie blue staining was used to ensure equal loading.",
    "ncbi_link": "Clpp: 53895
Eral1: 57837"
  },
  {
    "caption": "(D) Quantification of Western blot analysis of respiratory chain subunits upon knockdown of Eral1. Levels relative to wild type cells treated with control siRNA (set to 1) are presented. Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (COXI n=4; ATP5A1 n=2; the rest n=6). Combined results from 2-3 blots were used for quantification as only 2 samples of each conditions are used in a single experiment. Numbers within bars represent statistical difference to control wild type cells and numbers above bars represent difference in Clpp-knockout cells upon Eral1 siRNA.",
    "ncbi_link": "Clpp: 53895
Eral1: 57837"
  },
  {
    "caption": "(E) Western blot analysis of RC subunits upon Eral1 knockdown in MEFs. Cells (0) were treated with doxycycline for 48 hours (T) and upon doxycycline removal allowed to recover for 24 hours (R).(F) Quantification of the relative recovery of COXI and NDUFB6 upon Eral1 siRNA. The values are calculated as ratio between recovered (R) to doxycycline untreated (0) protein levels in Eral1-knockdown cells (Eral1) and compared to the same results obtained in control cells (Ctrl). Bars represent mean ± SD. Student's t-test was used to determine the level of statistical difference (COXI n=4; NDUFB6 n=3). Numbers within bars represent statistical difference between control/Eral1 siRNA treated cells and numbers above bars represent difference between +/+; Eral1 siRNA and -/-; Eral1 siRNA.",
    "ncbi_link": "Eral1: 57837"
  },
  {
    "caption": "(A) Sirt5 deficiency leads to higher ROS levels in MEFs. ROS levels were determined in the indicated MEFs as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments **p<0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(B) Sirt5 deficiency suppresses GSH production in MEFs. The ratio of [GSH/GSSG] was determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments *p<0.05 (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(C) Sirt5 deficiency inhibits NADPH production in MEFs. The ratio of [NADPH/NADP+] was determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(D) Sirt5 deficiency decreases cell growth. MEF cells were seeded in 6-well plates at a density of 50,000 cells/well, and cell growth rate was carefully monitored every 1-2 days by cell counting for 8 days. The results are average ± SD of 3 independent experiments *p<0.05, ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(E) Sirt5 deficiency leads to higher sensitivity of MEFs to Paraquat. The levels of cleaved PARP and Caspase-3 were determined by western blot analysis.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(F) Sirt5 protects MEFs from ROS-induced cell death. Wild-type and Sirt5 KO MEFs were treated with Paraquat (500 μM) for 24 hrs, and then cell viability was determined by counting the remaining adherent cells. The results are average ± SD of 3 independent experiments **p<0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(G-I) Sirt5 deficiency inhibits the production of NADPH and GSH and increases lipid peroxide in mouse brains after Paraquat injection. Female Sirt5 KO and WT littermates (n=3~5 per group) were intraperitoneally injected with saline or paraquat (10 mg/kg) once a week for 3 consecutive weeks. The ratios of [NADPH/NADP+] and [GSH/GSSG] and the level of lipid peroxide were determined in tissue extracts. The results are average ± SD. *p<0.05, n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(J-K) Sirt5 KO mice are more sensitive to Paraquat-induced nigrostriatal dopaminergic degeneration. Female Sirt5 KO and WT littermates were treated with paraquat as in (G-I). The brain sections were stained to detect tyrosine hydroxylase (TH) positive dopaminergic neurons in the SNc region, as described in 'Materials and Methods'. Representative immunohistochemistry images (original magnification, 100×; scale bar, 100 μm) and the corresponding quantifications are shown in (J) and (K), respectively. The results are average ± SD. *p<0.05, n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(A)Knockdown of SIRT5 inhibits NADPH production in HEK293T cells. The ratio of [NADPH/NADP+] was determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments **p<0.01, ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(B) Knockdown of SIRT5 suppresses GSH production in HEK293T cells. The ratio of [GSH/GSSG] was determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments **p<0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(C) Knockdown of SIRT5 leads to higher ROS levels in HEK293T cells. ROS levels were determined in the indicated stable cells as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(D) Knockdown of SIRT5 leads to higher sensitivity to Paraquat. The expression levels of PARP and Caspase-3 were determined by western blot analysis.",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(E) SIRT5 protects HEK293T cells from ROS-induced cell death. The indicated stable HEK293T cells were treated as mentioned above in (D), and then cell viability was determined by counting the remaining adherent cells. The results are average ± SD of 3 independent experiments **p<0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(G) The activities of G6PD/6PGD and IDH1/2 are reduced in stable HEK293T cells with SIRT5 knockdown. Activities of the indicated endogenous proteins were determined in cell extracts as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments *p<0.05, **p<0.01, ***p<0.001, n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(H) G6PD and IDH2 are activated by SIRT5 in vitro. Upon pre-incubation with SIRT5 in vitro, the activities of the indicated ectopically expressed proteins were determined as described in 'Materials and Methods'. The results are average ± SD of 3 independent experiments **p<0.01, n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(C) SIRT5 knockdown increases G6PD glutarylation and IDH2 succinylation, respectively, and decreases both enzyme activity. Flag-G6PD or Flag-IDH2 was ectopically expressed in the indicated stable HEK293T cells. G6PD/IDH2 proteins were purified by immunoprecipitated with Flag beads and eluted with Flag peptide, followed by determination of their lysine modifications and enzyme activity. The results are average ± SD of 3 independent experiments **p<0.01, ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "G6PD: 2539
IDH2: 3418
SIRT5: 23408"
  },
  {
    "caption": "(D) SIRT5 decreases G6PD glutarylation and IDH2 succinylation, and increases both enzyme activity. Flag-G6PD or Flag-IDH2 was co-overexpressed with HA-SIRT5 in HEK293T cells. G6PD and IDH2 proteins were purified by immunoprecipitation with Flag beads and eluted with Flag peptide, followed by determination of their lysine modifications and enzyme activity. The results are average ± SD of 3 independent experiments *p<0.05, **p<0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "G6PD: 2539
IDH2: 3418
SIRT5: 23408"
  },
  {
    "caption": "(F-G) K413 in IDH2 may be a key succinylation site that is directly targeted by SIRT5. The indicated Flag-tagged IDH2 proteins were overexpressed in HEK293T cells with stable SIRT5 knockdown or SIRT5 co-overexpression. Wild-type and mutant IDH2 proteins were purified by Flag beads and eluted with Flag peptide, followed by measurement of IDH2 enzyme activity. The results are average ± SD of 3 independent experiments *p<0.05, n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "IDH2: 3418
SIRT5: 23408"
  },
  {
    "caption": "(A-B) SIRT5 expression is not affected by chemical oxidant treatment. HEK293T cells were treated with Paraquat (A) or H2O2 (B) for the indicated periods. The mRNA and protein expression of endogenous SIRT5 were determined by quantitative real-time PCR and western blot analysis, respectively. The results are average ± SD of 3 independent experiments. n.s.: not significant (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "(F) Chemical oxidants enhance the ability of SIRT5 to activate IDH2. Flag-SIRT5 was ectopically expressed in HEK293T cells, and the transfected cells were treated with increased concentrations of Paraquat or H2O2 for the indicated periods. Flag-SIRT5 was purified by immunoprecipitation with Flag beads, eluted with Flag peptide, and then incubated with purified Flag-IDH2 in vitro. IDH2 enzyme activity was measured as described in 'Materials and Methods', normalized by its protein level. The results are average ± SD of 3 independent experiments **p<0.01, ***p<0.001 (two-tailed unpaired t-test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "Relative quantification of mRNA for Ppcs, Ppcdc, and Coasy by genotype from each of the three study regions. n=11,4,4 for WT and n=8,4,4 for KO (GP, SN, Cerebellum, respectively)",
    "ncbi_link": "Coasy: 71743
Ppcdc: 66812
Ppcs: 106564"
  },
  {
    "caption": "Relative mRNA expression of Tfrc, Ireb2, and Hamp by genotype and brain region. n=11,4,4 for WT and n=8,4,4 for KO (GP, SN, Cerebellum, respectively)",
    "ncbi_link": "Hamp: 84506
Ireb2: 64602
Tfrc: 22042"
  },
  {
    "caption": "Relative mRNA and protein expression of the dopamine receptor Drd1 compared by genotype, brain region and treatment status (pPanSH = 4'-phosphopantetheine). n=11,4,4 for WT and n=8,4,4 for KO (GP, SN, Cerebellum, respectively) QRT-PCR. n=5 for Western blot for all groups",
    "ncbi_link": "Drd1: 13488"
  },
  {
    "caption": "Relative mRNA expression of Drd2 and GABA receptor Gabra3 expression by genotype and brain region. n= same as 3A.",
    "ncbi_link": "Drd2: 13489
Gabra3: 14396
GABA receptor: 14396"
  },
  {
    "caption": "Relative quantification of COASY mRNA in human PKAN primary cell lines. n= 5 for both genotypes and cell types",
    "ncbi_link": "COASY: 80347"
  },
  {
    "caption": "Relative quantification of COASY/Coasy in fresh, blood-derived lymphocytes from human and mouse compared by genotype. n=51,35 for human (control, PKAN, respectively) and n=5 for both mouse genotypes.",
    "ncbi_link": "Coasy: 71743
COASY: 80347"
  },
  {
    "caption": "Relative mRNA expression of mitochondrially-encoded genes important for oxidative phosphorylation from complex I (MT-ND1), complex III (MT-CYB), cytochrome C (MT-CO1), and ATP synthase (MT-ATP6) in human mutant fibroblasts versus control cells. n=3 for both genotypes.",
    "ncbi_link": "ATP synthase: 4508
MT-ATP6: 4508
MT-CO1: 4512
cytochrome C: 4512
MT-CYB: 4519
MT-ND1: 4535"
  },
  {
    "caption": "Relative expression of Pank1α, Pank1β, total Pank1 and Pank3 in mouse brain regions. n=8,8,4 for both genotypes (GP, SN, Cerebellum, respectively).",
    "ncbi_link": "Pank1: 75735
Pank1α: 75735
Pank1β: 75735
Pank3: 211347"
  },
  {
    "caption": "Relative expression of Pank1α and Coasy in GP from WT and KO mice treated for 14 days with bezafibrate (0.8 mg/g body weight) or gemfibrozil (1.2 mg/g body weight). n=8 for both genotypes treated with vehicle, n=5 for both KO groups treated with either bezafibrate or gemfibrozil.",
    "ncbi_link": "Coasy: 71743
Pank1α: 75735"
  },
  {
    "caption": "Relative quantification of Coasy mRNA from GP compared by treatment status using four compounds: 4'-phosphopantetheine (pPanSH), pantetheine, vitamin B5, and CoA. n=8 (WT-veh), 5 (KO-veh), 5 (KO-pPanSH), 4 (KO-all other intermediates). Correction of Coasy, Tfrc, Ireb2, and Drd1 expression in GP by 4'-phosphopantetheine over a range of doses. n=8 (WT-veh), 5 (KO-veh), 5 (KO-0.82), 4 (WT-5), 5 (KO-5), 5 (KO-8.2), 5 (KO-10). 5 (WT-20), 5 (KO-20)",
    "ncbi_link": "Coasy: 71743
Drd1: 13488
Ireb2: 64602
Tfrc: 22042"
  },
  {
    "caption": "Relative quantification of COASY mRNA from human fibroblasts treated with pPanSH. n=3 for both genotypes.",
    "ncbi_link": "COASY: 80347"
  },
  {
    "caption": "Relative quantification of Coasy, Tfrc and Drd1 mRNA from GP by number of days post-cessation of treatment with 5μg of 4'-phosphopantetheine per g of body weight. n= 11 (WT-veh-D0), 5 (KO-veh-D0), 4 (WT-pPanSH-D0), 5 (KO-pPanSH-D0), 5 (KO-pPanSH-D1), 5 (KO-pPanSH-D2), 5 (KO-pPanSH-D3), 5 (WT-pPanSH-D7), 4 (KO-pPanSH-D7),",
    "ncbi_link": "Coasy: 71743
Drd1: 13488
Tfrc: 22042"
  },
  {
    "caption": "(A) ANAC032expression in WT plants sprayed with Pst DC3000, 6 and 24 hpi, compared to control (sprayed with 10 mM MgCl2 (Mock)). Error bars represent means ± SD (n = 3; 'n' represents independently performed experiments, each including the rosette leaves of at least three plants grown in individual pots). ANAC032expression in WT treated with (B) SA or MeJA or (C) COR for 3 and 6 h compared to non-treated controls. In B and C, means ± SD are given (n = 3; 'n' represents independently performed experiments, each including at least 20 seedlings). FCh, fold change. Asterisks indicate a significant difference from their respective controls (p < 0.01; Student´s t-test).",
    "ncbi_link": "ANAC032: 844081"
  },
  {
    "caption": "(B) Pst DC3000 growth in ANAC032 transgenics and WT plants 3 dpi after pressure infiltration. Two independent experiments were performed with three replications per experiment, each replicate consisting of three plants grown in individual pots (six measurements in total). The graph shows data points of the two individual experiments (I and II) along with their mean (Avg).",
    "ncbi_link": "ANAC032: 844081"
  },
  {
    "caption": "(E) Heat map showing the fold change (log2 basis) in the expression ratio of defense-/stress-related differentially expressed genes in anac032-1 and 35S:ANAC032 compared to WT after spraying with Pst DC3000 (6 hpi) normalised to their respective controls. Blue, downregulated; red, upregulated. Data represent means of three independent experiments, each including the rosettes leaves of at least three plants grown in individual pots. Asterisks indicate significant differences from WT plants (Student's t test, p ≤ 0.05).",
    "ncbi_link": "ANAC032: 844081
anac032: 844081"
  },
  {
    "caption": "(A) MYC2, PDF1.2A and NIMIN1 expression in ANAC032 transgenics compared to WT after spraying with Pst DC3000 (24 hpi) normalised to their respective controls. FCh, fold change. Means ± SD (n = 3; 'n' represents independently performed experiments, each including the rosette leaves of at least three plants grown in individual pots).",
    "ncbi_link": "MYC2: 840158
ANAC032: 844081
NIMIN1: 837800
PDF1.2A: 834469"
  },
  {
    "caption": "(B) EMSA showing binding of ANAC032 to MYC2, PDF1.2A and NIMIN1 promoter regions (in 5´-DY682-labelled double-stranded oligonucleotides) harbouring ANAC032 binding sites. 1, labelled probe only; 2, labelled probe plus GST protein 3, labelled probe plus ANAC032-GST protein; 4, labelled probe, ANAC032-GST protein and 100 x competitor (unlabelled oligonucleotide containing ANAC032 binding site).",
    "ncbi_link": "MYC2: 840158
NIMIN1: 837800
PDF1.2A: 834469"
  },
  {
    "caption": "(C) Confocal microscopy image showing nuclear localization of ANAC032-GFP fusion protein expressed from the ANAC032 promoter in ANAC032prom:ANAC032-GFP/anac032-1 seedlings treated with Pst at 6 hpi. Left, bright field; right, chlorophyll auto-fluorescence (red) and GFP fluorescence (green) under bright field.",
    "ncbi_link": "ANAC032: 844081
anac032: 844081"
  },
  {
    "caption": "(D) Expression of MYC2, PDF1.2A, NIMIN1 and ANAC032 in two-week-old ANAC032prom:ANAC032-GFP/anac032-1 seedlings compared to WT at 6 hpi with Pst, normalised to their respective controls. FCh, fold change. Means ± SD (n = 3; 'n' represents independently performed experiments, each including the rosette leaves of at least three plants grown in individual pots). Asterisks indicate a significant difference from WT, normalised to their respective controls (p < 0.05; Student´s t-test).",
    "ncbi_link": "MYC2: 840158
ANAC032: 844081
anac032: 844081
NIMIN1: 837800
PDF1.2A: 834469"
  },
  {
    "caption": "(E) ChIP-qPCR shows enrichment of MYC2, PDF1.2Aand NIMIN1 promoter regions containing ANAC032 binding site compared to a promoter region lacking the ANAC032 binding site (AT5G09810; Neg Cont). Means ± SD (n = 3; 'n' represents independently performed experiments, each including the rosette leaves of at least three plants grown in individual pots). Asterisks indicate a significant difference from negative control (p < 0.01; Student´s t-test).",
    "ncbi_link": "AT5G09810: 830841
MYC2: 840158
NIMIN1: 837800
PDF1.2A: 834469"
  },
  {
    "caption": "Transcript levels of (A) NIMIN1 and (B) PR1 in WT, anac032-1 and 35S:ANAC032 plants after 3 and 6 h of treatment with SA compared to their respective controls.",
    "ncbi_link": "ANAC032: 844081
anac032: 844081
NIMIN1: 837800
PR1: 815949"
  },
  {
    "caption": "(C), Expression of PDF1.2A in WT and anac032-1 plants after 3 and 6 h of treatment with SA compared to their respective controls. Transcript levels were measured using qRT-PCR and numbers on the y-axis indicate fold change (FCh; log2 basis). Means are shown ± SD (n = 3; 'n' represents independently performed experiments). Asterisks indicate a significant difference from wild type (p < 0.05; Student's t test).",
    "ncbi_link": "anac032: 844081
PDF1.2A: 834469"
  },
  {
    "caption": "(D) RNAscope in situ hybridization (Dand5, top; Negative probe (dapB); down) and hematoxylin staining of P5 mouse retinas.",
    "ncbi_link": "dapB: 
Dand5: 23863"
  },
  {
    "caption": " G Quantification analysis of changes in chromatin openness at Tgfb1 and Notum promoter regions by FAIRE-qPCR among different groups of NSPCs. Data are presented as mean ± SEM of three independent biological replicates, n = 3. Two-tailed unpaired Student's t-test was used to analyze statistical significance; P < 0.05, P < 0.01. ",
    "ncbi_link": "Notum: 77583
Tgfb1: 21803"
  },
  {
    "caption": " I, J Quantification analysis of expression changes of Mir-203 (I) and Bmi1 (J) by qRT-PCR among different groups of NSPCs. Data are presented as mean ± SEM of three independent biological replicates, n = 3. Two-tailed unpaired Student's t-test was used to analyze statistical significance; P < 0.05, P < 0.01. ",
    "ncbi_link": "Bmi1: 12151
Mir-203: 387199"
  },
  {
    "caption": "(a) Experimental testing of the predicted SR (DU) rescuers of DNMT1 via drug combination experiments in 18 NSCLC cell lines insensitive to Decitabine. The matrix displays drug interactions between Decitabine, a DNMT1 inhibitor, and inhibitors of its predicted rescuer genes (X-axis) across 18 NSCLC cell lines (Y-axis) that are insensitive to Decitabine. Row labels present rescuer genes and their inhibitors. Colors in the matrix show whether the interactions found are significantly synergistic (red), antagonistic (green) or non-significant (in gray). Values in the matrix show average synergism (<1 synergism and >1 antagonism Thirteen predicted DU-SR rescuers (red lines), two predicted DD SR rescuers (green lines) of DNMT1 and one random control (JAK3i) were tested.",
    "ncbi_link": "DNMT1: 1786
JAK3: 3718"
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post PD1/PDL1 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after anti-PD1 (b) Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post CTLA4 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after anti-CTLA4 (c) Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "The transcriptomic alterations of rescuer genes post PD1/PDL1 and CTLA4 blockade in patient tumor biopsies: Their post (vs. pre) treatment expression changes of DU/DD rescuers after PD1 + CTLA4 combination therapies (d). Each panel displays the expression fold change of each predicted rescuer gene (rows) for different tumor samples (columns) and the P-value of over-all paired Wilcoxon test of the expression changes observed in paired samples. Significantly altered up/down-regulated genes are marked by (*). Genes marked in red are those whose CRISPR knockdown enhances melanoma sensitivity to anti-PD1 blockade in mice models.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "I. U2OS cell lines conditionally expressing indicated GFP-FAM111A alleles were fixed at the indicated times after treatment with Doxycycline (DOX) to induce expression of the transgenes and stained with crystal violet.",
    "ncbi_link": "GFP: 
FAM111A: 63901"
  },
  {
    "caption": "G. Analysis of FAM111A interactors. U2OS/GFP-FAM111A WT cells were treated or not with DOX for 4 h, subjected to GFP immunoprecipitation (IP) and analyzed by mass spectrometry. Volcano plot shows enrichment of individual proteins (+DOX/-DOX ratio) plotted against the P value. Dashed lines indicate the significance thresholds (FDR<0.05; s0=1).",
    "ncbi_link": "GFP: 
FAM111A: 63901"
  },
  {
    "caption": "H. U2OS or U2OS/∆FAM111A cells were subjected to IP with IgG (control) or RFC1 antibody followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "B. Immunoblot analysis of U2OS cell lines left untreated or incubated in the presence of DOX to induce expression of the indicated GFP-FAM111A alleles. U2OS/GFP-FAM111A WT (low) cells express the transgene at a lower level than U2OS/GFP-FAM111A WT cells used in Figure 1 and 2 (see Figure EV4A).",
    "ncbi_link": "GFP: 
FAM111A: 63901"
  },
  {
    "caption": "Immunoblot analysis of cell lines treated or not with DOX in the absence or presence of Z-VAD-FMK. J. using U2OS cell lines conditionally expressing ectopic untagged FAM111A alleles.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "B. U2OS/GFP-FAM111A WT cells treated or not with DOX were subjected to GFP IP followed by immunoblotting with indicated antibodies. C. As in (B), using U2OS/GFP-FAM111B WT cells.",
    "ncbi_link": "GFP: 
FAM111A: 63901
FAM111B: 374393"
  },
  {
    "caption": "J. U2OS/GFP-FAM111B cell lines (Figure 5E) were fixed at the indicated times after DOX treatment and stained with crystal violet.",
    "ncbi_link": "GFP: 
FAM111B: 374393"
  },
  {
    "caption": "(A-C) Immunoblots of Gp96 and NMHCIIA levels from whole cell lysates (WCL) and Gp96 IP fractions (IP Gp96) of HeLa cells: (B) left uninfected (U) or infected with wt or Δhly Lm for 1 h. (A, C) Quantifications of NMHCIIA in IP Gp96 are the mean±SEM (n≥3) (a.u. - arbitrary units).",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "(F) Confocal microscopy images of HeLa cells infected with wt or Δhly Lm for 6 h immunolabelled for NMHCIIA (green), Gp96 (red) Lm (blue) and stained with DAPI (white). Arrows indicate NMHCIIA-Gp96 cortical bundles at cortical sites close to wt Lm. (D and F) Scale bar - 10 μm. See also Figs EV1 and EV2.",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "(A) Confocal microscopy images of shCtrl, shGp96 or shNMHCIIA HeLa cells treated with LLO (0.5 nM, 15 min) and immunolabelled for KDEL-proteins (blue), NMHCIIA (green) and Gp96 (red). Insets show compact NMHCIIA bundles in shCtrl cells and dispersed NMHCIIA bundles in shGp96 cells. Scale bar - 10 μm. (B-D) Quantification of the % of cells harbouring NMHCIIA bundles after incubation with (B) LLO (0.5 nM, 15 min), (C) aerolysin (0.2 nM, 40 min) or (D) with wt Lm. Values are the mean ±SEM (n≥3), p-values were calculated using (B-C) one-way-ANOVA with Dunnett post hoc analyses and (D) two-tailed un-paired Student's t-test, *p<0.5, ***p<0.001. For shNMHCIIA, bundles were detected following actin staining (Fig EV3C).",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(E-F) Number of (E) blebs per cell or (F) retracting blebs per cell evaluated by time-lapse microscopy analysis of LLO-treated shCtrl or shGp96 cells. shCtrl n=32 cells and shGp96 n=40 cells, p-values were calculated using two-tailed un-paired Student's t-test *p<0.5. (G) Sequential frames of time-lapse microscopy analysis of LLO-treated HeLa cells expressing GFP-NMHCIIA (shCtrl, shGp96 and shCtrl with 25 μM Blebbistatin - shCtrl-BB). LLO was added to culture medium 10 seconds before t0.",
    "ncbi_link": "Gp96: 7184"
  },
  {
    "caption": "(H) Immunoblots of Ser19-phosphorylated MRLC (pMRLC), MRLC and actin levels from shCtrl or shGp96 cells left untreated (U) or treated with 0.1 nM LLO for the indicated time points. Quantification of pMRLC levels corresponds to the mean ± SEM (n≥3), p-values were calculated using one-way-ANOVA with Tukey post hoc analyses **p<0.01, ***p<0.001. See also Appendix Fig S2 and Fig EV3.",
    "ncbi_link": "Gp96: 7184"
  },
  {
    "caption": "(E-F) Confocal microscopy images of shCtlr, shGp96 or shNMHCIIA HeLa cells stained for actin (red) and DAPI (blue) and immunolabelled for (E) NMHCIIA (green) or (F) focal adhesion kinase (FAK) (green). (A, D-F) Scale bar - 10 μm. Insets show sites with focal adhesion points and arrows indicate stress fibers or distinct focal adhesion points. Quantification of the % of cells with (G) stress fibers or (H) focal adhesion points labelled by FAK.",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(A) Epifluorescence microscopy images of supernatants from LLO-treated (0.5 nM 15 min) shCtlr, shGp96 or shNMHCIIA HeLa cells collected into poly-lysine-coated cover slips, fixed and stained with FITC-WGA (green) and DAPI (blue). Insets show PM blebs of variable sizes and DAPI staining confirms the absence of cell nuclei. Scale bar - 10 μm. (B) Quantification of released PM blebs (total FITCWGA/field). Values are the means ± SEM (n≥3). ***p<0.001.",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(C-E) Flow cytometry analysis of the % of PI-positive shCtlr, shGp96 or shNMHCIIA HeLa cells. Cells were treated with (C) 0.5 nM LLO for the indicated times. Levels of PI incorporation by untreated cells were subtracted from all LLO-treated samples. Values are the mean ± SEM (n≥4) and p-values were calculated using one-way-ANOVA with Tukey post hoc analyses *p<0.5, **p<0.01, ***p<0.001.",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(C-E) Flow cytometry analysis of the % of PI-positive shCtlr, shGp96 or shNMHCIIA HeLa cells. Cells were treated with (D) 1.5 or 3 nM LLO for 15 min; or (E) 0.1 nM LLO for 10 min followed by LLO washed out and recovery for indicated times. Levels of PI incorporation by untreated cells were subtracted from all LLO-treated samples. Values are the mean ± SEM (n≥4) and p-values were calculated using one-way-ANOVA with Tukey post hoc analyses *p<0.5, **p<0.01, ***p<0.001.",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(C-E) Flow cytometry analysis of the % of PI-positive shCtlr, shGp96 or shNMHCIIA HeLa cells. Cells were treated with (E) 0.1 nM LLO for 10 min followed by LLO washed out and recovery for indicated times. Levels of PI incorporation by untreated cells were subtracted from all LLO-treated samples. Values are the mean ± SEM (n≥4) and p-values were calculated using one-way-ANOVA with Tukey post hoc analyses *p<0.5, **p<0.01, ***p<0.001.",
    "ncbi_link": "Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(A-B) Epifluorecence microscopy images of HeLa cells (B) infected with GFP-expressing wt Lm for 6 h. Cells were incubated with exofacial-PS probe (Alexa-568 annexin A5) (red) 30 min prior fixation, immunolabelled for NMHCIIA (green) and stained with DAPI (blue). Insets show PM damage marked by exofacial-PS sites. Arrows indicate exofacial-PS associated with intracellular bacteria and in shCtrl cells with NMHCIIA bundles; arrowheads indicate NMHCIIA bundles associated with exofacial-PS sites without detectable bacteria.",
    "ncbi_link": "NMHCIIA: 4627"
  },
  {
    "caption": "(D-E) Flow cytometry analysis of the % of PI-positive shCtlr, shGp96 or shNMHCIIA HeLa and RAW264.7 cells, infected with GFP-expressing wt or Δhly Lm for 6 h. The levels of PI incorporation by uninfected cells were subtracted from infected samples. Values are the mean ± SEM (n≥4) and p-values were calculated using one-way-ANOVA with Tukey post hoc analyses *p<0.5, **p<0.01, ***p<0.001. PM permeability was assessed in cells harbouring equivalent numbers of intracellular bacteria (Fig Appendix Fig S3).",
    "ncbi_link": "hly: 987033
Gp96: 7184
NMHCIIA: 4627"
  },
  {
    "caption": "(A) Immunoblots of NMHCIIA and Gp96 levels from whole cell lysates (WCL) and IP fractions (IP Gp96) of extracts of zebrafish larvae 3 dpf uninfected (U) or infected with wt or ∆hly Lm (low dose 200-1500 CFU) for 24h.",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "(B) Immunoblots of Gp96 and tubulin levels from zebrafish 3 dpf larvae injected with control (Ctrl-mo) or Gp96 morpholino oligonucleotides (Gp96 mo).",
    "ncbi_link": "Gp96: 386590"
  },
  {
    "caption": "(C) Confocal microscopy images of zebrafish larvae (Ctrl mo or Gp96 mo) infected (low dose) in the tail muscle, with the GFP-expressing wt or Δhly Lm for 24 h, immunolabelled for KDEL-proteins (green), and stained with phalloidin (actin, red) and DAPI (white). Images show actin rich structures at the cell cortex (arrows) and ER-KDEL puncta (arrowheads) in larvae infected with wt strain.",
    "ncbi_link": "hly: 987033
Gp96: 386590"
  },
  {
    "caption": "(D) CFU counts per zebrafish larvae (Ctrl or Gp96 mo) infected with wt (low dose) or Δhly (high dose > 10,000 CFU) Lm and analysed at 0, 24, 48 hpi. Results are mean ± SEM (n≥3) (horizontal bars) and each circle represents 1 larvae. p-values were calculated using one-way-ANOVA with Tukey post hoc analyses **p<0.01.",
    "ncbi_link": "hly: 987033
Gp96: 7184"
  },
  {
    "caption": "(E) Survival curves of zebrafish larvae (Ctrl-mo or Gp96-mo) infected with a wt (low dose) or Δhly (high dose > 10,000 CFU) Lm. Results are the mean ± SEM (n≥3). wt infection of Ctrl and Gp96 mo, n=28 larvae; Δhly infection of Gp96 mo n=13. p-values were calculated using Log Rank test, **p<0.01.",
    "ncbi_link": "hly: 987033
Gp96: 386590"
  },
  {
    "caption": "(F) CFU counts per zebrafish larvae infected with a high dose of ∆hly Lm at different times post-infection. Results are mean ± SEM (n≥3) (horizontal bars); each point represents 1 larvae. See also Fig EV5.",
    "ncbi_link": "hly: 987033"
  },
  {
    "caption": "A Phenotypes of WT (Col-0), two gso1  mutant alleles (gso1-1, gso1-3) and two independent complementation lines (com-1, com-2). Seedlings  were grown on 1/2 MS for 6 days and then transferred to 1/2 MS medium supplemented with or without 100 mM NaCl  for 10 days. B,C Primary root length and seedling  fresh weight  of seedlings  depicted in (A) were measured at day 10 after transfer. (mean ± SEM, n = 10, P < 0.05, two-way ANOVA)",
    "ncbi_link": "gso1: 827760"
  },
  {
    "caption": "A Co-IP of GSO1  and SOS2  using Arabidopsis protoplasts  transiently expressing Myc-GSO1KD (GSO1  kinase domain) and Flag-SOS2, Flag-HA-SOS3  or Flag-SCaBP8. Protein extracts were immunoprecipitated  with anti-Myc  antibody and immunoblotted  with anti-Myc  antibody or anti-Flag  antibody.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
SCaBP8: 829437
GSO1: 827760
SOS2: 833502
SOS3: 832494"
  },
  {
    "caption": "D Phenotypes of WT (Col-0), gso1-3, sos2-2 and gso1-3 sos2-2. Seedlings  were grown on 1/2 MS medium for 6 days and then transferred to 1/2 MS supplemented with or without extra NaCl  for 10 days. E,F  Primary root length and fresh weight  of seedlings  depicted in (D) were measured at day 7 after transfer. (mean ± SEM, n = 10, P < 0.05, two-way ANOVA)",
    "ncbi_link": "gso1: 827760
sos2: 833502"
  },
  {
    "caption": "B Immunoblot  using anti-Myc  antibody and CBB  and autoradiograph  from kinase assays combining Myc-SOS2  with SOS1C300 as substrate. 10-day-old seedlings  stably expressing Pro35S:6Myc-SOS2  in Col-0 or gso1-3 were treated with or without 100 mM NaCl  for 12 h, and Myc-SOS2  protein immunoprecipitated  with anti-C-Myc  antibody-conjugated agarose  from roots  was used in the assays. Signal strength of the phosphorylation  bands has been calculated relative to the left lane.",
    "ncbi_link": "Myc: 
gso1: 827760
SOS2: 833502"
  },
  {
    "caption": "A Phenotypes of WT (Col-0), gso1-3, esb1, and casp1 casp3. Seedlings  were grown on 1/2 MS for 6 days and then transferred to 1/2 MS medium with or without 100 mM NaCl  for 10 days. B, C Primary root length and seedling  fresh weight  of seedlings  depicted in (A) were measured at day 10 after transfer. (mean ± SEM, n = 12, two-way ANOVA, P < 0.05)",
    "ncbi_link": "casp1: 818183
casp3: 817280
esb1: 817416
gso1: 827760"
  },
  {
    "caption": "G Phenotypes of WT (Col-0), cif1 cif2, and gso1-3. Seedlings  were grown on 1/2 MS medium for 6 days and then transferred to 1/2 MS medium supplemented with or without 100 mM NaCl  for 10 days.",
    "ncbi_link": "cif1: 2745542
cif2: 829612
gso1: 827760"
  },
  {
    "caption": "A-D Protein accumulation (A, C, D) or  gene expression  (B) of SOS2, CIF2, GSO1, and SGN1 displayed as false color fluorescence intensity. Seedlings  from the indicated plant lines were grown on 1/2 MS for 4-5 days and then transferred to 1/2 MS with or without 100 mM NaCl  for 1 day. Scale bars: 200 µm.",
    "ncbi_link": "CIF2: 829612"
  },
  {
    "caption": "H-I. Jmjd2a(+/-); Jmjd2a(+/-) (H) or Jmjd2b(+/-); Jmjd2b(+/-) (I) mice were inter-crossed and the number of pups alive at time of weaning reported. P values were calculated using a Chi-square test.",
    "ncbi_link": "Jmjd2a: 230674
Jmjd2b: 193796"
  },
  {
    "caption": "C-D. Jmjd2a(+/-); Jmjd2c(+/-) mice were inter-crossed. The number of (C) pups alive at weaning or (D) embryos recovered at E6.5 is presented. P values were calculated using exact binomial test with the most conservative estimate of expected (-/-;-/-) embryos (6.25 %, assuming no linkage between the Jmjd2a and Jmjd2cloci even though they are located on the same chromosome).",
    "ncbi_link": "Jmjd2a: 230674
Jmjd2c: 76804"
  },
  {
    "caption": "A. Examples of ChIP-seq data obtained for Jmjd2a, Jmjd2c (Pedersen et al, 2014), and H3K4me3.",
    "ncbi_link": "Jmjd2a: 230674
Jmjd2c: 76804"
  },
  {
    "caption": "B. Heat map showing H3K9me3 ChIP-seq data for Jmjd2a/c bound TSSs (+/- 5kb) sorted according to read number in 2abc #13+OHT.",
    "ncbi_link": "Jmjd2a: 230674"
  },
  {
    "caption": "C. ChIP-qPCR validations for selected Jmjd2a/c targets (see Fig 4G). Graphs show mean ± SD for technical triplicates and are representative of results obtained in at least 2 independent experiments.",
    "ncbi_link": "Jmjd2a: 230674"
  },
  {
    "caption": "C-D. Density plots showing average ChIP-seq signals for (C) H3K9me3 or (D) H3K36me3 with 95% confidence intervals of the mean indicated in grey. Plots are shown for genes, which are down- or up-regulated according to the microarray analyses (FDR<0.05, absolute fold change log2(|FC|)>0.5) for both 2ac and 2abc KO ESCs (overlaps presented in Appendix Fig S6A), or do not show strong expression changes (log2(|FC|) < 0.2). Genes are further classified as \"Bound\" if containing binding sites for both Jmjd2a and Jmjd2c within +/- 1kb of a TSS.",
    "ncbi_link": "Jmjd2a: 230674
Jmjd2c: 76804"
  },
  {
    "caption": "A-C. 2ac clones established after transfection with an empty vector (empty) or plasmids expressing wild type Jmjd2c (2c wt) or a catalytic mutant (2c mut) were exposed to OHT as indicated and subsequently used for (A) WB.",
    "ncbi_link": "Jmjd2c: 76804"
  },
  {
    "caption": "A-C. 2ac clones established after transfection with an empty vector (empty) or plasmids expressing wild type Jmjd2c (2c wt) or a catalytic mutant (2c mut) were exposed to OHT as indicated and subsequently used for (B) RT-qPCR analyses",
    "ncbi_link": "Jmjd2c: 76804"
  },
  {
    "caption": "A-C. 2ac clones established after transfection with an empty vector (empty) or plasmids expressing wild type Jmjd2c (2c wt) or a catalytic mutant (2c mut) were exposed to OHT as indicated and subsequently used for (C) serial plating for the generation of growth curves.",
    "ncbi_link": "Jmjd2c: 76804"
  },
  {
    "caption": "(D and E) Parent NIH3T3 cells, Atg4B mutant overexpressing NIH3T3 cells stably expressing GFP-tagged LC3, Atg5, WIPI-1, Atg14L1, Atg9L1, or ULK1 were transfected with Effectene-coated latex beads for 3 h and subjected to immunocytochemistry for galectin3. The percentages of Atg-positive per galectin3-positive beads were enumerated. At least 30 beads were counted (n = 3). The values are the mean ± SD.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "(E) wild-type MEFs, and Atg5-KO MEFs stably expressing GFP-tagged LC3, Atg5, WIPI-1, Atg14L1, Atg9L1, or ULK1 were transfected with Effectene-coated latex beads for 3 h and subjected to immunocytochemistry for galectin3. The percentages of Atg-positive per galectin3-positive beads were enumerated. At least 30 beads were counted (n = 3). The values are the mean ± SD.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(C) Purified recombinant GST or GST-Ub-immobilized glutathione Sepharose beads were incubated with lysates from HEK293T cells transiently expressing FLAG-tagged Atg16L1 constructs for 1 h at 25°C with gentle agitation. The beads were washed three times with ice-cold PBS and the bound complexes were eluted with 50 mM reduced glutathione and then subjected to Western blotting for FLAG.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(B) FIP200 binds to exogenously expressed Atg16L1. Myc-Atg16L1 coprecipitations with an empty vector control (lane 1) or One-STrEP-FLAG (OSF)-FIP200 (lane 2).",
    "ncbi_link": "FIP200: 9821"
  },
  {
    "caption": "(C) FIP200 binds endogenous Atg16L1. Atg16L1 coprecipitations with an empty vector control (lane 1) or OSF-FIP200 (lane 2).",
    "ncbi_link": "Atg16L1: 55054
FIP200: 9821"
  },
  {
    "caption": "(D) Wild-type or FIP200-KO MEFs stably expressing the empty vector, full-length Atg16L1, or ΔWD mutant were incubated in growth medium (−) or Earle's balanced salt solution (EBSS) (+) for 1 h and examined by Western blotting using the indicated antibodies. We previously reported that stable expression of an exogenous Atg16L1 construct can be used to replace the endogenous Atg16L1 protein with an exogenous Atg16L1 protein (Fujita et al., 2009) because free Atg16L1 molecules not complexed with the Atg12-Atg5 conjugate are preferentially degraded by the ubiquitin-proteasome system. In control cells (Empty), two Atg16L1 splicing variants, the α- and β-forms, were detected. In full-length β-form-replaced cells (Full), the α-form was not detected, whereas in ΔWD-replaced cells (ΔWD) both the α- and β-forms were minimally detected. Thus, we successfully obtained cells that express only endogenous levels of the full-length or ΔWD mutant.",
    "ncbi_link": "Atg16L1: 77040
FIP200: 12421"
  },
  {
    "caption": "(E-L) Atg16L1-replaced wild-type or FIP200-KO MEFs were infected with Salmonella (MOI = 10) for 1 h and subjected to immunocytochemistry for Atg16L1 and Ub (E and F) or LC3 and Ub (I and J). The percentages of Atg16L1-positive (G and H) or LC3-positive per Ub-positive bacteria were enumerated (K and L). At least 50 Salmonella were counted. The average ± SD is shown for three independent experiments. Statistical analysis was performed by Student's t test. *, P < 0.05; NS, not significant. Bar, 5 µm.",
    "ncbi_link": "Atg16L1: 77040
FIP200: 12421"
  },
  {
    "caption": "(E) The N-terminal 1-249 fragment of Atg16L1 is sufficient to interact with FIP200. Full-length (lanes 1 and 2) or the N-terminal 1-249 fragments (lanes 3 and 4) of Myc-Atg16L1 coprecipitations with empty vector controls (lanes 1 and 3) or OSF-FIP200 1276-1591 (lanes 2 and 4).",
    "ncbi_link": "Atg16L1: 55054
FIP200: 9821"
  },
  {
    "caption": "(F) Co-precipitation experiments confirming that OSF-FIP200 1276-1591 coprecipitates with wild-type (WT) Myc-Atg16L1 (1-249) fragments, but not with analogous fragments containing a mutant FIP200-binding site (Myc-Atg16L1 ΔWD 239-242A).",
    "ncbi_link": "Atg16L1: 55054
FIP200: 9821"
  },
  {
    "caption": "(B-E) Atg16L1-Δ/Δ MEFs stably expressing the indicated constructs were infected with Salmonella (MOI = 10) for 1 h and then analyzed by immunocytochemistry for LC3 (B) or Atg16L1 (D). Bar, 5 µm. The percentage of LC3- or Atg16L1-positive Salmonella per Ub-positive Salmonella was enumerated by fluorescence microscopy (C and E). At least 50 bacteria were counted. The average ± SD is shown for three independent experiments.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(F) Atg16L1-Δ/Δ MEFs stably expressing the indicated constructs were cultured in growth medium (Fed) or EBSS (Starved) for 1 h and then subjected to immunocytochemistry using an anti-LC3 antibody. The number of LC3 puncta in each cell was counted for more than 50 cells. The average ± SD is shown for three independent experiments.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(B-K') The Drosophila posterior midguts containing Su(H)-Gal4>UAS-CD8:GFP (Su(H)>GFP) with sucrose (Suc, control) (B-C'), P.e for 36 h (D-F'), Ecc15 for 36 h (G-I') and DSS for 36 h (J-K') were immunostained for GFP (green), PH3 (red) and DAPI (blue). (C-C', E-E', H-H' and K-K') Magnification of selected areas containing PH3+GFP─ cells from B, D, G and J. The EB cell close to the PH3+ cell (white arrow) in C-C' is out of focus. (F-F' and I-I') Magnification of selected areas containing PH3+ EBs (GFP+) from D and G. White arrowheads and red arrows indicate PH3 in GFP─ and GFP+ cells, respectively. (L and M) Quantification of PH3 GFP─ ISCs (L) and PH3+GFP+ EBs (M) with given treatments. n = 21 guts for each treatment.",
    "ncbi_link": "GFP: 
CD8: 12526///12525
Gal4: 855828
Su(H): 34881"
  },
  {
    "caption": "(D-F'') When the ISCs were marked by esgGal4, su(H)-Gal80>UAS-GFP, PH3 expression was found in GFP+ ISCs with feeding of Suc (control) (D-D''), P.e (E-E'') and Dss (F-F''). However, PH3 expression is present in EBs with GFP─Pros─ and small nuclei upon P.e infection (E-E'', red arrows). The white arrows indicate GFP+ cells with PH3 expression. (G) Quantification of PH3+GFP─Pros─ EBs with given treatments. n = 11 guts for each treatment. Data information: Three independent experiments were performed, and error bars are ± SEM. ***, P < 0.001 (Student's t-test) (G).",
    "ncbi_link": "GFP: 
esg: 34903
Gal4: 855828
Gal80: 854954
su(H): 34881"
  },
  {
    "caption": "(D-N') The Drosophila midguts expressing Su(H)ts>GFP with control (D-E'), UAS-RasV12 for 6 days (F-H'), EGFRA887T for 4 days (I-K') and UAS−λTop for 5 days (L-N') were immunostained for GFP (green), PH3 (red) and DAPI (blue). (E-E', G-G', J-J' and M-M') Magnification of selected areas containing PH3+GFP─ cells from D, F, I and L. (H-H', K-K' and N-N') Magnification of selected areas containing PH3+GFP+ cells from F, I and L. White arrowheads and red arrows indicate PH3 in GFP─ ISCs and GFP+ EBs, respectively. (O, P) Quantification of PH3+GFP─ (P) and PH3+GFP+ (O) in midguts with indicated genotypes. n = 13 guts for each genotype. (Q) Quantification of PH3+ EBs (GFP+) with the given genotypes in response to P. e infection. n = 11 guts for each genotype.",
    "ncbi_link": "GFP: 
λTop: 39564
EGFR: 37455
Ras: 43873
Su(H): 34881"
  },
  {
    "caption": "(B-C''') Flies expressing UAS-Flp; Su(H)ts UAS-CD8:GFP; ActP>Stop>LacZ were fed with Suc (B-B''') or P.e (C-C''') for 36h and their midguts were dissected and immunostained with antibodies against GFP, β-gal and Dl. Blue arrowheads indicate Dl+ ISCs; white arrows indicate GFP+ EBs; and red arrowheads indicate EB progeny cells (LacZ+GFP─). (D) Quantification of Dl+ ISC-like cells from EBs (GFP─LacZ+Dl+) in the control, P. e infected midguts, n=50. (E) Quantification of Dl+ ISC-like cells from EBs (GFP─LacZ+Dl+) in the control with Suc or P. e, or knockdown of EGFR with Suc or P. e infection, n=50.",
    "ncbi_link": "Flp: 
GFP: 
LacZ: 
ActP: 31521
CD8: 12526///12525
EGFR: 37455
Stop: 252732
Su(H): 34881"
  },
  {
    "caption": "(A-C''') The midguts from adult female flies expressing UAS-Flp; Su(H)ts UAS-CD8:GFP; ActP>Stop>LacZ with (B-B''') or without (A-A''') UAS-RasV12 or with UAS-RasV12 and UAS-stg-RNAi (C-C''') were dissected and immunostained with antibodies against GFP, β-gal and Dl. The bigger GFP─ nucleus with LacZ expression (only red arrowheads) indicate differentiating or mature ECs. Blue arrowheads indicate Dl+ ISCs; white arrows indicate GFP+ EBs; and red arrowheads indicate EB progeny cells (LacZ+GFP─). (D) Quantification of Dl+ ISC-like cells from EBs (GFP─LacZ+Dl+) in the indicated genotypes, n=50.",
    "ncbi_link": "Flp: 
GFP: 
LacZ: 
ActP: 31521
CD8: 12526///12525
Ras: 43873
stg: 43466
Stop: 252732
Su(H): 34881"
  },
  {
    "caption": "(C-E'') The representative twin clones from midguts when EGFRA887T is overexpressed in EBs (D-D'', red and green arrows) or adult flies were fed with P.e for 36h (E-E'', red and green arrows), but no twin clone is found in the control (C-C''). (F) Quantification of different types of twin clones in the control midguts, or in the midguts with EGFRA887T overexpression or P.e infection. n = 10 guts for each genotype.",
    "ncbi_link": "EGFR: 37455"
  },
  {
    "caption": "(A-C'') ISCs from EBs upon RasV12 expression or P. e infection could differentiate to generate EE or pre-EE cells (B-C'', LacZ+Pros+GFP─, blue arrowheads), but no EE or pre-EE cells from EBs are found in the control (A-A'', white arrowheads). (D) Quantification of EE cells from progenies of EBs with indicated genotypes or treatments. n = 9 guts for each genotype or treatment.",
    "ncbi_link": "Ras: 43873"
  },
  {
    "caption": "(A) Example regions exhibiting the IPOD-HR occupancy  where EPOD calls are made. Loose EPODs (pink) and Strict EPODs (teal) represent spans of high  protein occupancy at lower and higher thresholds, respectively. Neighboring areas showing lower robust z scores  are not EPODs. Note that following the definitions in [12], the presence of an EPOD requires a sustained region of high average occupancy, without any regions in which occupancy drops to background levels. Thus, breaks in EPOD calls represent cases where a rolling average occupancy drops below the calling threshold (e.g., the breakpoint in the middle of pinQ  in the top panel), and regions of apparent occupancy may nevertheless not be called due to being below the minimum length threshold (as is the case for nohA).",
    "ncbi_link": "nohA: 946021
pinQ: 946088"
  },
  {
    "caption": "(E) Specific locations across all conditions remain occupied by protein where EPODs across a representative region, the waa operon, were called (left) and unoccupied by RNA polymerase (right). The quantile normalized robust z scores of the protein occupancy at each 5 bp are represented by the IPOD-HR occupancy.",
    "ncbi_link": "waa: 948146///948145///948147///948151///948155///948150///948143///948148///948142///948140///948149///948135///948136///948144"
  },
  {
    "caption": "(E) Protein occupancy  over the waa  operon. The quantile normalized  robust z scores of the  protein occupancy  at each 5 bp are represented by the  IPOD-HR occupancy. The EPOD over the waa  operon is lost in the ∆stpA∆hns  condition which results in increased accessibility and  RNA polymerase occupancy",
    "ncbi_link": "hns: 945829
stpA: 947130
waa: 949048///948144///948136///948135///948149///948140///948142///948148///948143///948150///948155///948151///948147///948145///948146
waa: 948146///948145///948147///948151///948155///948150///948143///948148///948142///948140///948149///948135///948136///948144///949048"
  },
  {
    "caption": "(G) RNA-seq  analysis shows log fold change compared to WT of waa operon expression  upon deletion of hns  and stpA. (*) indicate q value < 0.05 = *, < 0.005 = **, < 0.0005 = ***",
    "ncbi_link": "hns: 945829
stpA: 947130"
  },
  {
    "caption": "(B) Protein occupancy over the idn  operon for each condition (colors are denoted in (A)). The quantile normalized robust z scores of the  protein occupancy at each 5 bp are represented by the  IPOD-HR occupancy. There is a large loss in protein occupancy when cells are shifted to 5KDG, leading to the loss of the call ed EPOD. Protein occupancy is restored once cells are grown in the second glucose  condition. The 500bp normalized average of previously published H-NS ChIP-seq [20] exhibits high  H-NS binding  on the idnD  promoter region.",
    "ncbi_link": "idnD: 944769"
  },
  {
    "caption": "(B) Difference in Log2 ratio of fitnesses of the KDG-exposed cells with unexposed lacZ::cat  relative to that observed prior to KDG  exposure, given as a function of time  since exposure to KDG. Day -1 corresponds to the day before KDG  exposure, Day 0 is cells taken immediately after growth  in KDG, and subsequent timepoints  reflect different durations of growth  in M9 Min Glu  prior to competition (See (A)). Points show medians across replicates (3 biological replicates for 0.5 days, 6 biological replicates for all other timepoints); error bars show 95% confidence intervals for the difference relative to the Day -1 timepoint, calculated using the R wilcox.test function. Significance was assessed using a Wilcoxon rank sum test comparing the distribution at each timepoint  to the -1 day (naive) timepoint: *, p<0.05; **, p<0.005.",
    "ncbi_link": "cat: 
lacZ: 945006"
  },
  {
    "caption": "(A) Example prophage  region that is annotated with the Fis- and Hfq-associated HMM class 5 in our genome-wide HMM classification The quantile normalized robust z scores of the  protein occupancy  at each 5 bp are represented by the  IPOD-HR occupancy. Prophage  genes are highlighted with a red box. The major peak associated with WT IPOD-HR occupancy is represented in a grey dashed line as a reference to compare  IPOD-HR occupancy in the other genotypes. Modest loss of  protein occupancy was observed at the same prophage-containing EPOD for ∆fis  (light purple; see color key in (B)) and ∆hfq  (dark purple; see color key in (B)) conditions compared to WT (gold).",
    "ncbi_link": "fis: 947697
Fis: 947697
hfq: 948689
Hfq: 948689"
  },
  {
    "caption": "(B)  RNA-seq  of WT, ∆fis, and ∆hfq  were performed. The log fold change compared to WT was calculated at prophage  genes contained in the dashed box in (A). Induction of prophages  across the region where loss in occupancy is observed. (*) indicate the adjusted p-value: <0.10 = +, < 0.05 = *, <0.005=**, <0.0005=***",
    "ncbi_link": "fis: 947697
hfq: 948689"
  },
  {
    "caption": "(F) Rate ratios of all genes (grey) and prophage  genes (red) in each quadrant outline in (E), showing a higher rate of genes that resided in the +/+ category, indicating that many prophages  are de-repressed in both ∆fis  and ∆hfq. (*) indicate the p-value calculated from testing the null that the rate ratios are the same. P-value < 0.05 = *, <0.005=**, <0.0005=***",
    "ncbi_link": "fis: 947697
hfq: 948689"
  },
  {
    "caption": "(G) P1 vir transduction  experiment to test the viability  of ∆fis  and ∆hfq. -Hfq  indicates deleting Hfq  and -CspE  indicates deleting -CspE  as a control. Strain identities are indicated in the box. Number of transductions  were counted on LB + Kan  plates; all efficiencies are relative to WT, and thus the log-scaled relative transduction rate for the WT itself is 0 by definition. -R1 indicates that the prophage region in (A) was deleted to test whether the loss of prophages silenced by Fis  and Hfq  restored viability  of a ∆fis  ∆hfq  genotype. R2 and R3 were other regions in the genome that contained prophages that appeared to have Fis/Hfq  dependent EPODs. Plotted values are mean efficiencies across replicates, with error bars showing a 95% credible interval obtained via Bayesian inference, assuming the replicate-level colony counts are Poisson distributed with a (conjugate) Gamma(0,0) prior; all log ratios (including error bounds) are plotted relative to the mean WT value. Data obtained from 5 biological replicates for hfq::kan  transductions  and 4 biological replicates for cspE::kan  transductions.",
    "ncbi_link": "CspE: 947024
cspE: 947024
fis: 947697
Fis: 947697
hfq: 948689
Hfq: 948689"
  },
  {
    "caption": "(C) Effects of deletion of rok  in the vicinity of an nEPOD; Rok ChIP  data from[70] shows a strong overlap with the nEPOD boundary, whereas that occupancy region is lost in Δrok cells.",
    "ncbi_link": "rok: "
  },
  {
    "caption": "(A, Neutrophils  isolated from tamoxifen-treated Nlrp3A350V/wt CreT+ and Nlrp3A350V/wt CreT- mice  were incubated with LPS  (3 hr) before culture media were analysed for secreted IL-1β (A) Cytokine values represent mean ± SEM of n=3 biological repeats. Statistical significance was analysed by two-way ANOVA and P-values were corrected for multiple comparisons (Bonferroni). **, p ≤ 0.01.",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799"
  },
  {
    "caption": "B). Neutrophils  isolated from tamoxifen-treated Nlrp3A350V/wt CreT+ and Nlrp3A350V/wt CreT- mice  were incubated with LPS  and cell lysates  and culture media were immunoblotted  for β-actin, caspase-1  and IL-1β (B).",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799"
  },
  {
    "caption": "(C) Representative pictures of Nlrp3A350V/wt MRP8-CreTg and Nlrp3A350V/wt MRP8-Cre- mice  on days 4 and 8 after birth. Left side in each picture: Nlrp3A350V/wt MRP8-Cre- mice; right side in each picture: Nlrp3A350V/wt MRP8-CreTg. Abscesses  (day 4) and  scaling erythema (day 8) are observed in Nlrp3A350V/wt MRP8-CreTg mice.",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799
MRP8: 20201"
  },
  {
    "caption": "(D) Survival curves of  Nlrp3A350V/wt MRP8-CreTg (n=22) and littermate Nlrp3A350V/wt MRP8-Cre- (n=21) mice. Statistical significance was analysed by the log-rank Mantel-Cox test. ****, p ≤0.0001.",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799
MRP8: 20201"
  },
  {
    "caption": "(E) Representative H&E-stained  sections of spleen  (top, scale bar: 100 µM) and liver  (bottom, scale bar: 200 µM) of Nlrp3A350V/wt MRP8-CreTg and littermate Nlrp3A350V/wt MRP8-Cre- mice. Spleens  of Nlrp3A350V/wt MRP8-Cre- control mice  (top left) display characteristic white pulp (WP) regions (example shown surrounded by dashed line) composed of  lymphoid follicles and periarteriolar lymphoid sheaths (PALS), which at this magnification are recognized by dark-purple staining, large aggregates of lymphocytes  surrounding the central artery (CA) and their distinctive separation from the red-staining red pulp (RP). WP  was largely absent in spleens of Nlrp3A350V/wt MRP8-CreTg (top middle). Megakaryocytes  (MK) are indicated for easier recognition of areas of extramedullary hematopoiesis (EMH). Most of the spleen parenchyma of Nlrp3A350V/wt MRP8-CreTg animals was replaced by EMH  of mostly myeloid  lineage, which can be recognized by the medium-sized cells with more cytoplasm, giving a lighter appearance (inset). In both the overview picture (top middle picture) and inset (top right) of Nlrp3A350V/wt MRP8-CreTg spleen, a small amount of EMH  of the erythroid  lineage is present that can be recognized by small aggregates of darker-stained, smaller cells (asterix,*). Liver  sections of both  Nlrp3A350V/wtMRP8-Cre- control mice  and diseased Nlrp3A350V/wt MRP8-CreTg pups  displayed comparable EMH  of the erythroid lineage (bottom left picture, indicated with yellow arrows). Liver  sections of Nlrp3A350V/wt MRP8-CreTg pups  also showed a modest increase in EMH  of the myeloid  lineage (bottom middle picture and inset (scale bar: 100 µM) in bottom right, indicated with yellow arrowheads), as well as hepatocyte  enlargement. (F-I) H&E-stained histological  sections of spleen (F, G) or liver (H, I) of Nlrp3A350V/wt MRP8-Cre- (Cre-, n=8) and Nlrp3A350V/wt MRP8-CreTg (CreTg, n=6) mice  were assigned a score of 0-5 for lymphoid  depletion (F) or EMH (G, H) or hepatocyte  enlargement (I) by a board-certified pathologist. Values represent mean ± SEM of n=6-8 biological repeats. Statistical significance was analysed by the Mann-Whitney U-test. ***, p ≤0.001.",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799
MRP8: 20201"
  },
  {
    "caption": "(J-L) Cytokine secretion analysis  (Luminex) of serum  samples obtained at day 7 from Nlrp3A350V/wt MRP8-Cre- (Cre-, n=8) and Nlrp3A350V/wt MRP8-CreTg (CreTg, n=6) pups. Values represent mean ± SEM of n=6-8 biological repeats. Statistical analysis of serum cytokine levels  was performed by the Welch's t-test. *, p ≤0.05; **, p ≤0.01.",
    "ncbi_link": "Cre: 2777477
Nlrp3: 216799
MRP8: 20201"
  },
  {
    "caption": "(C) Levels of mucosal vtRNA2-1, vtRNA1-1, vtRNA1-2, and vtRNA1-3 in the colon of patients with active ulcerative colitis (UC). Values are the means ± SEM (n = 6 per group). Unpaired, two-tailed Student's t test was used. * P < 0.05 compared with controls. (D) Levels of tissue vtRNAs in the ileal mucosa of patients with Crohn's disease (CD). Values are the means ± SEM (n = 6 per group). Unpaired, two-tailed Student's t test was used. * P < 0.05 compared with controls.",
    "ncbi_link": "vtRNA1-1: 56664
vtRNA1-2: 56663
vtRNA1-3: 56662
vtRNA2-1: 100126299"
  },
  {
    "caption": "(A) Association of vtRNA2-1 with HuR in Caco-2 cells as measured by biotin-labeled RNA pull-down assays. After cytoplasmic lysates were incubated with biotinylated vtRNA2-1, levels of HuR and other proteins in the pull-down material were assessed. Three separate experiments showed similar results.",
    "ncbi_link": "vtRNA2-1: 100126299"
  },
  {
    "caption": "(D) Changes in the expression levels of claudin-1, occludin, and E-cadherin proteins 48 h after cells were transfected with HuR expression vector alone or co-transfected with HuR and vtRNA2-1 expression vectors.",
    "ncbi_link": "HuR: 
vtRNA2-1: 100126299"
  },
  {
    "caption": "Macrophages  were detected by immunoblotting  with indicated antibodies (n = 3). Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. EPOR-KO macrophages  were PMs  isolated from EPOR-MKO mice.",
    "ncbi_link": "EPOR: 13857"
  },
  {
    "caption": "Macrophages  were detected by immunoblotting  with indicated antibodies (n = 3). Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. EPOR-KO macrophages  were PMs  isolated from EPOR-MKO mice.",
    "ncbi_link": "EPOR: 13857"
  },
  {
    "caption": "Macrophages  were detected by immunoblotting  with indicated antibodies (n = 3). Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. EPOR-KO macrophages  were PMs  isolated from EPOR-MKO mice.",
    "ncbi_link": "EPOR: 13857"
  },
  {
    "caption": "Flag-Aβ42  was injected into the  lateral ventricles of Lyz2-Cre+/+/Epor+/+ mice  (EPOR-C) (8 w) mice  pretreated with rhEPO  10000 IU/kg/d, i.p.) for 2 days (twice per day) (n = 3). One day later, Flag-Aβ42  in spleens  and brains  was detected by immunoblotting  (A, Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "ncbi_link": "Flag: 
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105"
  },
  {
    "caption": "Flag-Aβ42  was injected into the  lateral ventricles  of Lyz2-Cre+/+/Epor+/+ mice  (EPOR-C) (8 w) mice  pretreated with ARA290  (0.03 mg/kg/d, i.p.) for 2 days (twice per day) (n = 3). One day later, Flag-Aβ42  in spleens  and brains  was detected by immunoblotting  B, Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. ARA, ARA290",
    "ncbi_link": "Flag: 
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105"
  },
  {
    "caption": "Flag-Aβ42  was injected into the  lateral ventricles of Lyz2-Cre+/+/Eporloxp/loxp mice  (EPOR-MKO) (8 w) mice  pretreated with rhEPO 10000 IU/kg/d, i.p.) for 2 days (twice per day) (n = 3). One day later, Flag-Aβ42  in spleens  and brains  was detected by immunoblotting  Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "ncbi_link": "Flag: 
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105"
  },
  {
    "caption": "Flag-Aβ42  was injected into the  lateral ventricles of Lyz2-Cre+/+/Eporloxp/loxp mice  (EPOR-MKO) (8 w) mice  pretreated with ARA290  (0.03 mg/kg/d, i.p.) for 2 days (twice per day) (n = 3). One day later, Flag-Aβ42  in spleens  and brains  was detected by immunoblotting  E). Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. ARA, ARA290",
    "ncbi_link": "Flag: 
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105"
  },
  {
    "caption": "APP/PS1-21 mice  (5 m) treated with rhEPO (10000 IU/kg/d) or ARA290  (0.03 mg/kg/d) (i.p., once a day, for 14 days) (n=10), and Aβ plaques   in cortex  and hippocampus  (n = 5) were detected by IHC  (I). Data information: For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. ARA, ARA290; IHC, Immunohistochemical staining.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Proteins were extracted from spleens  of 5- or 11-month-old APP/PS-1-21+/+/Lyz2-Cre+/+/Eporloxp/loxp mice  (APP/PS1-21+EPOR-MKO) or APP/PS-1-21+/+/Lyz2-Cre+/+/Epor+/+ mice  (APP/PS1-21+EPOR-C), and soluble Aβ  levels were measured by ELISA  (n = 5) (J Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. ELISA, ",
    "ncbi_link": "APP: 351
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105
PS-1: 5663
PS1: 5663"
  },
  {
    "caption": "11-month-old APP/PS-1-21+/+/Lyz2-Cre+/+/Eporloxp/loxp mice  (APP/PS1-21+EPOR-MKO) or APP/PS-1-21+/+/Lyz2-Cre+/+/Epor+/+ mice  (APP/PS1-21+EPOR-C), Aβ plaques  in the cortex  and hippocampus  of mice  of 11-month-old (M) (n = 5) were detected by IHC. Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. IHC, Immunohistochemical staining.",
    "ncbi_link": "APP: 351
Cre: 2777477
Epor: 13857
EPOR: 13857
Lyz2: 17105
PS-1: 5663
PS1: 5663"
  },
  {
    "caption": "Both non-cognitive and cognitive behavioral  impairments of APP/PS1-21 mice  (11 m) were analyzed by nest construction assay, social interaction assay, NORT, FCT  (n = 10). Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. NORT,  novel object recognition test; FCT,  fear conditioning test.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Splenic macrophages  from APP/PS1-21 (5- or matched WT mice were detected by immunoblotting  with the indicated antibodies (n = 3) (A, Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Splenic macrophages  from APP/PS1-21 11-month-old) or matched WT mice  were detected by immunoblotting  with the indicated antibodies (n = 3) B). Data information: Unpaired t-tests were used for the comparison of two groups. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Old APP/PS1-21 mice  (11 m) and WT mice  at the same age were treated with rhEPO (10000 IU/kg/d), ARA290  (0.03 mg/kg/d) or vehicle (i.p., once a day, for 14 days). Splenic macrophages  were isolated for detection by immunoblotting  with the indicated antibodies (n = 3) (G). Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Old APP/PS1-21 mice  (11 m) and WT mice  at the same age were treated with rhEPO (10000 IU/kg/d), ARA290  (0.03 mg/kg/d) or vehicle (i.p., once a day, for 14 days). Protein levels of IDE  and NEP  were detected by immunoblotting  with indicated antibodies (n = 3) (I). Data information: vehicles were PBS. For multiple groups, one-way ANOVA was used. Results are presented as mean ± s.d., *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; ns denotes no statistical significance. IDE, insulin degrading enzyme; NEP, neprilysin.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "G-I MDM were treated with 5μM ETO for 18h and infected in the presence of ETO with HIV-1 BaL and DNA isolated 18 h post‐infection for qPCR.2LTR circles. (n = 3, mean ± s.e.m.; *P‐value ≤ 0.05, paired t‐test).",
    "ncbi_link": "2LTR circles: "
  },
  {
    "caption": "G-I MDM were treated with 5μM ETO for 18h and infected in the presence of ETO with HIV-1 BaL and DNA isolated 18 h post‐infection for qPCR.Integrated copies of viral DNA, Alu-Gag qPCR. (n = 3, mean ± s.e.m.; ***P‐value ≤ 0.001, paired t‐test).",
    "ncbi_link": "viral DNA: "
  },
  {
    "caption": "MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with VSV‐G HIV‐1 GFP and SIVmac virus‐like particles containing Vpx/Vpr (SIV VLP) or deleted for Vpx (SIV VLP del Vpx) or deleted for Vpr (SIV VLP del Vpr). Cells from a representative donor were used for immunoblotting. The percentage of infected cells was quantified by the automated cell‐imaging system Hermes WiScan and ImageJ 48h post-infection. (n = 4, mean ± s.e.m.; **P‐value ≤ 0.01; (ns) non‐significant, paired t‐test).",
    "ncbi_link": "Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "D-F. MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIVmac virus‐like particles containing Vpx/Vpr (SIV VLP). DNA was isolated 18 h post‐infection for qPCR quantification of F. Late RT products; G. 2LTR circles; H integrated viral DNA.Late viral RT products. AZT: MDM treated with 20μM AZT, a reverse-transcriptase inhibitor, were used as control. (n = 3, mean ± s.e.m.; (ns) non‐significant, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: 
Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "D-F. MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIVmac virus‐like particles containing Vpx/Vpr (SIV VLP). DNA was isolated 18 h post‐infection for qPCR quantification of F. Late RT products; G. 2LTR circles; H integrated viral DNA.2LTR circles. (n = 3, mean ± s.e.m.; (ns) non‐significant; *P‐value ≤ 0.05, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: 
Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "D-F. MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIVmac virus‐like particles containing Vpx/Vpr (SIV VLP). DNA was isolated 18 h post‐infection for qPCR quantification of F. Late RT products; G. 2LTR circles; H integrated viral DNA.Integrated copies of viral DNA, Alu-Gag qPCR. (n = 3, mean ± s.e.m.; (ns) non‐significant; **P‐value ≤ 0.01, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: 
Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "A-B. MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with VSV‐G HIV‐1 GFP and SIVmac virus‐like particles containing Vpx wild type (WT)/Vpr or Vpx Q76A mutant/Vpr (SIV VLP Q76A). (n = 3, mean ± s.e.m.; (ns) non‐significant; *P‐value ≤ 0.05; **P‐value ≤ 0.01, paired t‐test).MDM were differentiated and cultured in Human serum instead of FCS.",
    "ncbi_link": "Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "A-B. MDM were treated with 5μM ETO for 18h and co‐infected in the presence of ETO with VSV‐G HIV‐1 GFP and SIVmac virus‐like particles containing Vpx wild type (WT)/Vpr or Vpx Q76A mutant/Vpr (SIV VLP Q76A). (n = 3, mean ± s.e.m.; (ns) non‐significant; *P‐value ≤ 0.05; **P‐value ≤ 0.01, paired t‐test).MDM were differentiated and cultured in FCS. A standard culture condition used in all experiments. See Materials and Methods.",
    "ncbi_link": "Vpr: 956112
Vpx: 1490006"
  },
  {
    "caption": "C-F. MDM we treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIV VLP Q76A. DNA was isolated 18 h post‐infection for qPCR quantification of D. Late RT products; E. 2LTR circles; F. integrated viral DNA.Late viral RT products. AZT: MDM treated with 20μM AZT, a reverse-transcriptase inhibitor, were used as control. (n = 3, mean ± s.e.m.; (ns) non‐significant; *P‐value ≤ 0.05, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: "
  },
  {
    "caption": "C-F. MDM we treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIV VLP Q76A. DNA was isolated 18 h post‐infection for qPCR quantification of D. Late RT products; E. 2LTR circles; F. integrated viral DNA.2LTR circles. (n = 3, mean ± s.e.m.; (ns) non‐significant; *P‐value ≤ 0.05, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: "
  },
  {
    "caption": "C-F. MDM we treated with 5μM ETO for 18h and co‐infected in the presence of ETO with HIV-1 BaL and SIV VLP Q76A. DNA was isolated 18 h post‐infection for qPCR quantification of D. Late RT products; E. 2LTR circles; F. integrated viral DNA.Integrated copies of viral DNA, Alu-Gag qPCR. (n = 3, mean ± s.e.m.; *P‐value ≤ 0.05; **P‐value ≤ 0.01, paired t‐test).",
    "ncbi_link": "2LTR circles: 
viral DNA: "
  },
  {
    "caption": "MDM were treated with 5μM ETO for 18h, 3μg/ml cGAMP and 10ng/ml IFNβfor 18h. RNA was isolated and qPCR performed for selected genes using TaqMan assays. Expression levels of target genes were normalised to GAPDH. (n = 3, mean ± s.e.m.; *P‐value ≤ 0.05; (ns) non‐significant, paired t‐test).",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "B atg19Δ cells containing HTB‐Atg19 were grown to mid‐log phase. Atg19 was affinity purified and subjected to mass spectrometric phosphorylation mapping. Phosphorylation sites: enlarged; lysine substitutions: gray; Atg11 binding region: green.",
    "ncbi_link": "Atg11: 856162
Atg19: 854072
atg19: 854072"
  },
  {
    "caption": "C atg19Δ cells containing GFP‐Atg19 wild‐type or mutants as indicated were grown to mid‐log phase. Processing of endogenous Ape1 was analyzed by Western blotting and quantified by calculating the ratio of cleaved versus uncleaved Ape1 normalized to the wild‐type. Atg19 expression was assessed by anti‐GFP Western blotting.",
    "ncbi_link": "Atg19: 854072
atg19: 854072"
  },
  {
    "caption": "D atg19Δ GFP‐Atg11 Atg1‐TAP cells containing myc‐Atg19 as indicated were grown to log phase. Atg11 was immunoprecipitated, and bound Atg19 was analyzed by Western blotting.",
    "ncbi_link": "Atg1: 852695
Atg11: 856162
Atg19: 854072
atg19: 854072"
  },
  {
    "caption": "E GST‐fused propeptide of Ape1, Atg19 as indicated, and a His‐tagged fragment of Atg11 (amino acids 685-1178) were purified from Escherichia coli, mixed, and propeptide‐bound proteins were isolated and analyzed by Coomassie staining. Quantification of three individual experiments is shown. Error bars represent standard deviation.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "A GFP‐Atg11 Ape1‐mRuby atg19Δ cells containing myc‐Atg19 as indicated and Cup1‐Ape1 were grown to log phase. Overexpression of Ape1 was induced by addition of 250 μM copper sulfate for 3 h, and autophagy was induced by treating cells for 1 h with rapamycin. Scale bar, 5 μm.",
    "ncbi_link": "Ape1: 853758
Atg11: 856162
Atg19: 854072
atg19: 854072
Cup1: 856450"
  },
  {
    "caption": "B Ape1‐mRuby atg19Δ cells containing GFP‐Atg19 wild‐type or GFP‐Atg19‐3A were analyzed in log phase. Scale bar, 5 μm.",
    "ncbi_link": "Atg19: 854072
atg19: 854072"
  },
  {
    "caption": "C GFP‐Atg8 Ape1‐mRuby atg19Δ cells containing myc‐Atg19 as indicated and Cup1‐Ape1 were analyzed as in (A). Scale bar, 5 μm.",
    "ncbi_link": "Ape1: 853758
Atg19: 854072
atg19: 854072
Atg8: 852200
Cup1: 856450"
  },
  {
    "caption": "B atg34Δ yeast cells containing HTB‐Atg34 were grown to mid‐log phase and treated with rapamycin. Atg34 was affinity purified and subjected to mass spectrometric phosphorylation mapping. Phosphorylation sites: enlarged; Atg11 binding region: green; lysine substitution: gray.",
    "ncbi_link": "Atg11: 856162
Atg34: 854071
atg34: 854071"
  },
  {
    "caption": "C Ams1‐GFP atg19Δatg34Δ cells containing protein A (Stag)‐tagged Atg34 as indicated were starved for 4 h. Processing of endogenous Ams1‐GFP was analyzed by Western blotting and quantified by calculating the ratio of free GFP versus uncleaved Ams1‐GFP normalized to the wild‐type. Expression of Atg34 proteins was assessed by anti‐protein A Western blotting.",
    "ncbi_link": "Ams1: 852721
atg1: 852695
atg34: 854071"
  },
  {
    "caption": "F In vitro phosphorylation of recombinant Atg19, Atg19‐3A, and Atg19‐3D using wild‐type and kinase‐dead Atg1‐D211A as described in (E).",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "A Wild‐type, hrr25‐ts, and hrr25‐ts cells containing HRR25 on a centromeric plasmid were grown to mid‐log phase at 18°C followed by 2 and 4 h of log‐phase growth at 37°C. Ape1 processing was analyzed by Western blotting.",
    "ncbi_link": "HRR25: 855897
hrr25‐ts: 855897"
  },
  {
    "caption": "B atg19Δ and atg19Δ hrr25‐ts cells containing GFP‐Atg19 as indicated were analyzed for Ape1 processing in log phase after 2 h at 37°C.",
    "ncbi_link": "Atg19: 854072
atg19: 854072
hrr25‐ts: 855897"
  },
  {
    "caption": "C GFP‐Atg11, GFP‐Atg11 hrr25‐ts, and GFP‐Atg11 atg1‐D211A cells were analyzed for GFP‐Atg11 dot formation. Quantification of at least 70 cells in three individual experiments is shown. Error bars represent standard deviation. Scale bar, 3 μm.",
    "ncbi_link": "atg1: 852695
Atg11: 856162
hrr25‐ts: 855897"
  },
  {
    "caption": "D GFP‐Atg11, GFP‐Atg11 hrr25‐ts, and GFP‐Atg11 atg19Δ cells containing BFP‐Ape1 and Cup1‐Ape1 were grown to log phase. Overexpression of Ape1 was induced by addition of 250 μM CuSO4 for 3 h. coloc.: Cells with GFP‐Atg11/BFP‐Ape1 co‐localization. n = 50 (wt), 84 (hrr25‐ts), 127 (atg19Δ). Scale bar, 3 μm.",
    "ncbi_link": "Ape1: 853758
Atg11: 856162
atg19: 854072
Cup1: 856450
hrr25‐ts: 855897"
  },
  {
    "caption": "E Hrr25 was immunoprecipitated from Hrr25‐TAP cells and as a control from a non‐tagged wild‐type strain. In vitro phosphorylation of recombinant Atg19, Atg19‐3A, Atg34, and GST using the kinase‐bound beads was performed as described in Fig E. Both Atg19 panels are from the same gel with the same exposure.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "Confocal images of tPH-CynA-KikGR (green) and PH-Crac (red) expressing wild-type Dictyostelium AX3 cells (left) and PI3K1-2- Dictyostelium cells (right) treated with 5 µM Latrunculin A.",
    "ncbi_link": "PI3K1: "
  },
  {
    "caption": "(L) Representative confocal images of tPH-CynA-KikGR in wild-type Dictyostelium AX2 or RacH− cells treated with 5 μM latrunculin A Scale bar: 5 μm. (M) Ratio of membrane to cytosol intensity of tPH-CynA-KikGR in wild-type Dictyostelium AX2 and RacH− cells. T-test was carried out by GraphPad Prism, ****P ≤ 0.0001 versus AX2 group; mean ± SEM (n = 33).",
    "ncbi_link": "RacH: 8617155"
  },
  {
    "caption": "B Activity of each allele at 10 positive control SNPs and 1 negative control SNP in stimulated T cells. GATA1, NF-κB, and RUNX1 constructs were designed to include a binding site for the indicated transcription factors (+) or with that site disrupted (-). Fixed effects meta-analysis P value is shown: *<0.05; **<0.01, ***<0.001, ****<0.0001. Box and whisker plots represent median and IQR (box) and min-to-max (whiskers).",
    "ncbi_link": "GATA1: 2623
NF-κB: 4790
RUNX1: 861"
  },
  {
    "caption": "D Expression-modulating effect of each SNP [log2(OR)] as measured in MPRA and validation experiments. OR were calculated using the median activity of allelic constructs and are presented with respect to the risk allele (luciferase: n=5, MPRA: n=12).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": " B Pie chart depicting Bayesian fine-mapping results for an AS-associated locus on 2p15 (left panel). MPRA results in stimulated T cells (right panel) showing that rs6759298 has a significant expression-modulating effect (the strongest of any variant at this locus) while the other candidate SNPs have negligible effects. ",
    "ncbi_link": "2p15: 
rs6759298: "
  },
  {
    "caption": " C GWAS results (Liu et al, 2015) at a Crohn's disease and multiple sclerosis-associated locus on 6p23 (left panel). MPRA for candidate SNPs in stimulated T cells (right panel) identifying a SNP (rs34421390) with by far the greatest expression-modulating effect at this locus (blue, risk allele reduces expression; red, risk allele increases expression). Dotted horizontal line represents significance threshold (corrected for multiple-testing). ",
    "ncbi_link": "rs34421390: "
  },
  {
    "caption": "D GWAS results at a Type 1 Diabetes-associated locus on 14q32 (Onengut-Gumuscu et al, 2015; left panel). MPRA for the candidate SNPs in stimulated T cells (right panel). The construct with the largest and most significant effect contains the risk alleles for 2 SNPs (rs1988588 and rs3902659), each of which has a smaller effect when tested individually (position indicated by vertical dotted line). Dotted horizontal line represents significance threshold (corrected for multiple-testing).",
    "ncbi_link": "rs1988588: 
rs3902659: "
  },
  {
    "caption": "C A single variant (rs6927172) has the largest and most significant expression-modulating activity in resting (left panel) and stimulated CD4 T cells (right panel) with the risk allele reducing transcription. Plots represent median and IQR (box) and min-to-max (whiskers). FDR-corrected meta-analysis P value shown.",
    "ncbi_link": "rs6927172: "
  },
  {
    "caption": " E Allele-specific NF-κB binding in CD4 T cells from rs6927172 heterozygotes, demonstrating reduced NF-κB binding to the risk allele following stimulation (n=8; one-sample t-test, two-tailed). ",
    "ncbi_link": "rs6927172: "
  },
  {
    "caption": " G Genome-wide H3K27ac ChIP-seq in stimulated CD4 T cells from major- and minor-allele homozygotes at rs6927172 (n=6). Upper panels show input-normalised H3K27ac signals plotted against enhancer rank. Super-enhancers are defined above the inflection point of the curve. Lower panels show H3K27ac reads from a major (left) and a minor (risk) allele homozygote (right) in a 9kb window around rs6927172. ",
    "ncbi_link": "rs6927172: "
  },
  {
    "caption": "I Expression of genes on 6q23 in CD4 T cells from 131 patients with active IBD, stratified by rs6927172 genotype (qPCR; one-way ANOVA). Error bars represent SD. Expression of IL20RA and IL22RAR2 not detected.",
    "ncbi_link": "rs6927172: 
IL20RA: 53832
IL22RAR2: 116379"
  },
  {
    "caption": "D Expression of genes on 6q23 in EU-containing mRNA (EU added at time of stimulation) showing that deletion of the NF-κB binding site specifically reduces transcription of TNFAIP3, but not other genes at this locus (n=6; one sample t-test). Representative data from the DH gRNA combination.",
    "ncbi_link": "NF-κB: 4790
TNFAIP3: 7128"
  },
  {
    "caption": " G Secretion of effector cytokines following deletion of the NF-κB binding site - Th1 (left panel, IFNγ), Th17 (centre panel, IL-17A) and Th2 subsets (right panel, IL-4) (n=6, paired t-test, one-tailed). ",
    "ncbi_link": "NF-κB: 4790"
  },
  {
    "caption": "F-G.  Primary root length and  Lateral root  density of 21-day-old, mock- and SA190-colonized Col-0, aba2-1 and qpyr/pyl  plants upon growth  for 16 days on ½ MS + 25% PEG. Data information: Boxplot shows data from three independent biological replicates (technical replicates n = 36) where whiskers represents minimum and maximum values, \"+\" indicates mean and horizontal line represents median. Asterisks indicate the statistical differences based on the Student's t-test (* p < 0.05, *** p < 0.001).",
    "ncbi_link": "aba2: 841665"
  },
  {
    "caption": "B. Relative  gene expression  of aquaporin PIP  and TIP genes by qRT-PCR analysis normalized to tubulin  levels in 21-days old mock- and SA190-colonized roots of Arabidopsis  grown for 16 days on ½ MS with or without 25% PEG. Data information: Values represent the means of three biological experiments. Error bars indicate SE. All plots represent the mean of 3 biological replicates (biological replicates n= 3). Asterisks indicate a statistical difference based on the Student's t-test (* p < 0.05; ** p < 0.01; *** p < 0.001).",
    "ncbi_link": "tubulin: 836391"
  },
  {
    "caption": "C. Relative  gene expression of aquaporin PIP and TIP genes by  qRT-PCR analysis in Col-0, aba2-1 and qpyr/pyl mutants normalized to tubulin  levels in 21-days old mock- and SA190-colonized roots  of Arabidopsis  grown for 16 days on ½ MS with or without 25% PEG. Data information: Values represent the means of three biological experiments. Error bars indicate SE. All plots represent the mean of 3 biological replicates (biological replicates n= 3). Asterisks indicate a statistical difference based on the Student's t-test (* p < 0.05; ** p < 0.01; *** p < 0.001).",
    "ncbi_link": "aba2: 841665
tubulin: 836391"
  },
  {
    "caption": "Relative enrichment of the H3K4me3 mark at the indicated gene loci of selected PIPs and TIPs of non-colonized (Mock) and SA190-colonized (SA190) plants in Col-0 and aba2-1 mutant as determined by chromatin immunoprecipitation-qPCR  (ChIP-qPCR). The regions targeted for amplification are labelled as R1, R2 and R3. R1 encompasses 5'-UTR, R2 is close to the transcription start site (TSS) while R3 is outside the gene body. Amplification values were normalized to input and H3  and region 3 (R3) of non-colonized (Mock) Col-0 plants. The plots represent the means of 2 biological replicates. Error bars represent SE. (ns) non-significant Asterisks indicate a statistical difference based on 2-way ANOVA (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001 for p value differences between the conditions when compared to Col-0 Mock using Dunnett's multiple comparison test).",
    "ncbi_link": "aba2: 841665"
  },
  {
    "caption": "A-B. Total fresh weight  of 21 days old non-colonized- (Mock) and SA190-colonized (SA190) Col-0, tip2;1  and qpip  plants grown for 16 days under normal (½ MS) or drought stress proxy conditions (½ MS + 25% PEG). Data information: All plots represent the mean of 3 biological replicates. Error bars represent SE. Boxplot shows data from three independent biological replicates (technical replicates n = (A) 16-20, (B) 8-20 where whiskers represents minimum and maximum values, \"+\" indicates mean and horizontal line represents median. Asterisks indicate the statistical differences based on the Student's t-test (* p < 0.05, *** p < 0.001). Asterisks indicate a statistical difference based on the Student's t-test *** p < 0.001).",
    "ncbi_link": "tip2;1: 820870"
  },
  {
    "caption": "(B) Immunoblotting (IB) analysis of wild type (WT) and PAQR3-deficient MEFs after GS for different time as indicated.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(C) WT and PAQR3-deficient MEFs were treated with 80 mM chloroquine (CQ) for 2 h to induce LC3-II accumulation. Whole-cell lysates were harvested for IB analysis of LC3-II.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(D) Autophagosome-like structures in WT and PAQR3-deleted MEFs were detected after GS for 4 h by transmission electron microscopy. * indicates autophagosome-like structures. N, nucleus.(E) Quantitative analysis of autophagic vacuoles in transmission electron microscopy images. Thirty cells were quantified from each independent experiment，which was repeated for three times with similar results. Values are presented as mean ± SD, ***p < 0.001.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(F) Immunofluorescence staining of LC3 in WT or PAQR3-deficient MEFs after GS for 4 h. The arrowhead indicates representative LC3-positive puncta. Scale bar: 10 μm.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(G, H) HeLa cells were infected by PAQR3 knockdown or overexpression lentivirus together with their respective control virus. After GS for 1 h, the cell lysates were harvested for IB.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(A~C) HeLa cells stably expressing GFP-DFCP1 were transfected with or without PAQR3-specific shRNA. GFP signals were observed in these cells before or after glucose starvation (GS, shown in A). The knockdown efficiency of PAQR3 is shown in B and the statistics of GFP-positive puncta per cell is illustrated in C. Values are presented as mean ± SD, *** P < 0.001. Scale bar: 10 μm.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(D) GFP-WIPI1 was transfected into WT or PAQR3-deficient MEFs. 24 h later, the cells were incubated under GS for 4 h, followed by fluorescence observation. Scale bar: 10 μm.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(E) Different VPS34 complexes of WT or PAQR3 knockout HeLa cells were immunoprecipitated by ATG14L and UVRAG antibodies respectively in normal medium (NM) or GS. Then PI(3)P level was determined by a quantitative ELISA assay. The PI(3)P level was normalized to the amount of ATG14L or UVRAG used in the assay (n = 5; ***p < 0.001; ns, not significant).",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(F) HeLa cells infected with control or PAQR3-overexpressed lentivirus were treated with GS for 4 h. PI(3)P levels were determined as in Figure 2E(n = 5; **p < 0.01; ns, not significant).",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(G, H) PAQR3 knockout HeLa cells were transfected with plasmids of multiple PAQR3 deletion mutants. At 24 h after the transfection, the cell lysates were used to immunoprecipitate VPS34 complex by ATG14L antibody, followed by immunoblotting. The activity of ATG14L-linked VPS34 activity was detected by a quantitative ELISA assay. The PI(3)P level was normalized to the amount of ATG14L (n = 5; **p < 0.01).",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(B) Cytosol and Golgi fractionations were isolated from the livers of PAQR3-deleted mice and their littermate controls. Equal protein amounts of cytosol and Golgi fractions were subjected to IB.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(F) The lysates of WT or PAQR3 knockout MEFs were used in IP and IB.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(G) MEFs were infected with control or PAQR3-expressing lentivirus. Then a quantitative immunodepletion assay was performed with increasing amounts of the indicated antibodies. Supernatants of MEF lysates after immunodepletion (Post-IP) were examined to determine the level of VPS34 complex proteins.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(E) Purified GST or GST-fused PAQR3 (1-71) (GST fused NH2-terminal 71aa of PAQR3) on glutathione agarose beads was mixed with purified His tagged proteins as indicated. After incubation at 4 °C for 3 h, the samples were washed extensively and subjected to IB.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(F, G) Different PAQR3 deletion constructs were co-transfected with Flag-tagged Beclin1 (F) into HEK293T cells. The cells were then subjected to IP and IB.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(C) WT or AMPKa1/2 double knockout MEFs were incubated under NM or GS for 4 h, followed by IB with Phos-tag gel or regular SDS-PAGE.",
    "ncbi_link": "AMPKa1: 105787"
  },
  {
    "caption": "(E) Bacterial purified His-tagged NH2-terminal 71 amino acid of PAQR3 was incubated with or without purified Flag-tagged ATG14L. Then the complexes were treated with WT AMPK or DN-AMPK (dominant negative AMPK) for the indicated time in vitro. PAQR3 phosphorylation was examined by Phos-tag gel.",
    "ncbi_link": "ATG14L: 22863"
  },
  {
    "caption": "(F) HeLa cells infected with control or ATG14L-expressing lentivirus were incubated under GS for different time as indicated. Whole cell lysates were analyzed by both Phos-tag gel and regular SDS-PAGE.",
    "ncbi_link": "ATG14L: 22863"
  },
  {
    "caption": "(G) HeLa cells were infected by lentivirus expressing control shRNA or ATG14L-specific shRNA. Then the ATG14L knockdown cells were stably re-expressed with shRNA-resistant ATG14L (rATG14L) or Beclin1 and incubated under NM or GS for 4 h. Whole cell lysates were analyzed by both Phos-tag gel and regular SDS-PAGE.",
    "ncbi_link": "ATG14L: 22863"
  },
  {
    "caption": "(A) Bacterial purified His-tagged WT or T32A NH2-terminal 71aa of PAQR3 was incubated with or without Flag-tagged ATG14L purified from HEK293T cells. Then the complexes were incubated with AMPK for the indicated time and subjected to Phos-tag gel or regular SDS-PAGE.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(B) PAQR3-deficient HeLa cells were transfected with WT or T32A mutants of PAQR3 plasmids. 24 h later, the cells were incubated with normal medium (NM) or glucose starvation (GS) for 4 h, followed by immunoblotting (IB) in Phos-tag gel or regular SDS-PAGE.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(E) WT, phosphorylation defective (T32A), or phospho-mimetic (T32E) PAQR3 were transfected in the presence or absence of constitutively active AMPK (CA-AMPK) into PAQR3-deficient HeLa cells as indicated. 24 h later, the cells without AMPK transfection were treated with GS for 4 h. 10% of the cell lysates were subjected to IB to detect PAQR3 expression level (shown in Appendix Fig S4A), the remaining cell lysates were used to immunoprecipitate VPS34 complexes by ATG14L antibody, followed by VPS34 activity measurement by a quantitative PI(3)P ELISA assay. The PI(3)P level was normalized to the amount of ATG14L (n = 5; *p < 0.05; **p < 0.01 as compared to the first group).",
    "ncbi_link": "AMPK: 
PAQR3: 152559"
  },
  {
    "caption": "(F) PAQR3-deficient HeLa cells were infected with lentivirus expressing WT or T32A PAQR3. Then PAQR3 expression levels were examined by IB.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(G) Both WT HeLa cells and PAQR3 knockout HeLa cells infected with lentivirus expressing WT or T32A PAQR3 were treated with GS for 2 h or 4 h respectively. Cell lysates were analyzed by IB.",
    "ncbi_link": "PAQR3: 152559"
  },
  {
    "caption": "(A, B) Representative immunohistochemical images of LC3 staining in skeletal muscle (A) and liver (B) after 80 min exercise in WT and PAQR3-deleted mice. Scale bar in (A): 20 μm. Scale bar in (B): 50 μm.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(C, D) Immunoblotting analysis of skeletal muscle (C) and liver (D) from WT or PAQR3 knockout mice at rest or after 80 min exercise.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(E) Abnormal limb-clasping of PAQR3 knockout mice when suspended by its tail. Quantification scoring of the limb clasping phenotype is shown on the right (n = 7 for each group; **p < 0.01).",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "(H) The supernatants of liver lysates form WT or PAQR3 knockout mice were subjected to gel filtration analysis, followed by IB.",
    "ncbi_link": "PAQR3: 231474"
  },
  {
    "caption": "Representative images of the size of Mex3a mutant mice and control littermates at postnatal day (P)15. Scale bar, 1 cm. Genotypes were confirmed by Mex3a mRNA ISH in intestinal tissue (right panels). Scale bars, 50 μm. The offspring number (n) and observed genotype frequencies (%) resulting from heterozygous crosses are indicated below.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Absolute weight of Mex3a KO mice and control littermates at different ages. Data is represented in a box and whiskers plot as mean (middle line) with the minimum and maximum distribution values. Each point depicts one animal (WT: P1, n = 15; P8, n = 36; P15, n = 43; P22, n = 14; Adult, n = 14; Mex3a+/-: P1, n = 24; P8, n = 90; P15, n = 90; P22, n = 37; Adult, n = 21; Mex3a-/-: P1, n = 9; P8, n = 24; P15, n = 26; P22, n = 14; Adult, n = 8) ***P = 0.0003, ****P < 0.0001, two-way ANOVA test.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Kaplan-Meier survival curves for the different Mex3a genotypes (n = 80 for each genotype) ****P < 0.0001, Log-rank (Mantel-Cox) test.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Macroscopic assessment of the gastrointestinal tract of Mex3a KO and WT mice. These images are representative of the phenotype observed in mutant animals euthanized at different postnatal days. Boxed areas depict the distal small intestinal section (ileum) used for subsequent immunohistochemical analyses.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "H&E staining of a Mex3a KO and WT littermate at P19. Inserts depict high magnification of the boxed areas.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Average crypt depth (C) of WT animals (n = 3, > 40 crypts counted per animal) and Mex3a mutants (n = 6, > 20 crypts counted per animal). Also shown is the average villi height (D) of WT animals (n = 3, > 25 villi counted per animal) and Mex3a mutants (n = 6, > 15 villi counted per animal). Data is represented as mean ± standard error between P16 and P18. *P = 0.03, ***P = 0.0006, Student`s t test.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "mRNA ISH staining for the stem cell markers (H) Lgr5, (I) Olfm4, (J) Lrig1, and (K) Hopx in ileal sections of Mex3a mutants and littermate controls at P19. Inserts depict high magnification of the boxed areas.",
    "ncbi_link": "Hopx: 74318
Lgr5: 14160
Lrig1: 16206
Mex3a: 72640
Olfm4: 380924"
  },
  {
    "caption": "qPCR analysis of the expression level of the indicated stem cell markers in freshly isolated crypt fractions from Mex3a KO and WT animals (n = 3 of each genotype). Data is represented as mean fold-change plus standard error in Mex3a KO mice relatively to WT animals (dashed line). *P = 0.0208, **P < 0.01, ***P = 0.0007, Student`s t test.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Quantification of the size (diameter length) of Mex3a KO and WT organoid-initiating structures 2 days after crypt isolation (n = 3 for each genotype, > 150 structures counted in total). Data is represented in a box and whiskers plot as mean (middle line) with the minimum and maximum distribution values. Each point depicts one organoid-initiating structure. ****P < 0.0001, Student`s t test. Phase contrast microscopy images of intestinal organoids generated by Mex3a-/- and WT crypts 6 days after crypt isolation. Scale bars, 100 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Representative phase contrast microscopy images of Mex3a KO and WT intestinal organoids at days 2 and 4 of culture after 10 weekly passages. Scale bars, 100 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "qPCR analysis of crypt lineage marker genes in organoid cultures at day 2. Data is presented as the mean fold-change plus standard error (n = 4 for each genotype) for target gene expression in Mex3a KO intestinal organoids relative to WT (dashed line). *P < 0.05, Student`s t test.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Immunohistochemistry staining for the Paneth cell marker LYZ1 in Mex3a KO and WT intestinal organoid sections at day 2 of culture. Scale bars, 50 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "qPCR analysis of crypt lineage marker genes in organoid cultures at day 4. Data is presented as the mean fold-change plus standard error (n = 4 for each genotype) for target gene expression in Mex3a KO intestinal organoids relative to WT (dashed line).",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "mRNA ISH staining for the stem cell markers Mex3a, Lgr5, Hopx and Lrig1 in Mex3a KO and WT intestinal organoid sections at day 2 of culture. Scale bars, 50 μm.",
    "ncbi_link": "Hopx: 74318
Lgr5: 14160
Lrig1: 16206
Mex3a: 72640"
  },
  {
    "caption": "Representative images of immunofluorescence staining for the proliferation marker KI67 and BrdU incorporation in Mex3a KO and WT animals. Mice were injected at P17 and sacrificed at P20 (n = 3 for each genotype). Scale bars, 50 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Hierarchical clustering of samples (n = 3 for each genotype) and heatmap of differentially expressed genes between the Mex3a-/- and WT mice. The red colour represents over-expression, while the blue colour under-expression.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "GSEA pre-ranked analysis comparing the Mex3a-/- transcriptional profile against (E) the Mex3ahigh",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "GSEA pre-ranked analysis comparing the Mex3a-/- transcriptional profile against the Lgr5high and (G) the Wnt signalling pathway gene signatures.",
    "ncbi_link": "Lgr5: 14160
Mex3a: 72640"
  },
  {
    "caption": "qPCR analysis of selected genes in a cohort of independent mice. Data is presented as the mean fold-change of target gene expression in 2 biological replicates (Mex3a-/- Vs WT #1 and Mex3a-/- Vs WT #2) of Mex3a KO intestinal crypts relative to the respective WT controls (dashed line).",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Immunohistochemistry staining for PPARγ in Mex3a KO and WT mice ileum. Inserts depict high magnification of the boxed areas. Scale bars, 50 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Pparg mRNA ISH in ileal sections of Mex3a mutants and littermate controls at P18. Inserts depict high magnification of the boxed areas. Scale bars, 50 μm.",
    "ncbi_link": "Mex3a: 72640
Pparg: 19016"
  },
  {
    "caption": "qPCR analysis of PPARγ transcriptional targets in organoid cultures at day 4. Data is presented as the mean fold-change plus standard error (n = 3 for each genotype) for target gene expression in Mex3a KO intestinal organoids relative to WT (dashed line).",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Representative phase contrast microscopy images of Mex3a KO and WT intestinal organoids after 5 days of treatment with 50 μM Pioglitazone or vehicle (DMSO). Scale bars, 100 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "qPCR analysis of Lgr5, Pcna and Angptl4 expression in organoid cultures after 5 days of treatment with 50 μM Pioglitazone. Data is presented as the mean fold-change plus standard error (n = 4 for each genotype) for target gene expression in Pioglitazone-treated organoids relative to the DMSO vehicle (dashed line). * P = 0.02, Student`s t test.",
    "ncbi_link": "Angptl4: 57875
Lgr5: 14160
Pcna: 18538"
  },
  {
    "caption": "Representative phase contrast microscopy images of Mex3a KO and WT intestinal organoids at day 1 after passaging Pioglitazone- or vehicle (DMSO)-treated organoids. Scale bars, 100 μm.",
    "ncbi_link": "Mex3a: 72640"
  },
  {
    "caption": "Transposon screen validation of UBX5. ubx5∆ restores the growth of tdp1wss1. Cells were grown in YEPD and spotted on a medium supplemented with 1 mM auxin (for tdp1-degron degradation) and 5 μg/mL Camptothecin (CPT). Plates were incubated for 2 days at 30°C.",
    "ncbi_link": "tdp1: 852525
UBX5: 851930
ubx5: 851930
wss1: 856536"
  },
  {
    "caption": "Ubx5 levels are decreased in tdp1wss1. (E) HA-Ubx5 protein levels at steady state are compared by immunoblotting in different mutants. Mutant strains carrying the additional ubx5∆ mutation were complemented with a plasmid expressing HA-tagged Ubx5 from the endogenous pUBX5 promoter. 1mM auxin was added where indicated for 6 h to degrade tdp1-degron, when present. Pgk1 was used as a loading control.",
    "ncbi_link": "HA: 
tdp1: 852525
ubx5: 851930
Ubx5: 851930
UBX5: 851930
wss1: 856536"
  },
  {
    "caption": "The UBX∆ mutant of Ubx5 is sufficient to suppress FA and HU sensitivities of wss1∆. ubx5∆wss1∆ mutants were complemented with plasmids encoding HA-Ubx5-WT or HA-Ubx5 mutants overexpressed from the pGAL promoter; cells were grown in SC-trp and either treated with 40 mM FA for 15 min or spotted directly on 20 mM HU. Plates were prepared either with glucose (no HA-Ubx5 expression) or galactose (HA-Ubx5 expression) as the source of sugar. Plates were incubated for 2.5 days at 30°C. o/e, overexpression.",
    "ncbi_link": "HA: 
GAL: 855828
Ubx5: 851930
ubx5: 851930
wss1: 856536"
  },
  {
    "caption": "(B) The ubx5∆ mutation rescues growth defects caused by Flp-nick galactose-induction in the tdp1∆ wss1∆ top1∆ mutant. Indicated strains were grown in YEP-2% raffinose prior to plating on YEP-2% glucose or YEP-2% galactose plates. Plates were incubated for 3 days at 30°C.",
    "ncbi_link": "tdp1: 852525
top1: 854156
ubx5: 851930
wss1: 856536"
  },
  {
    "caption": "(E) Ubx5 occupancy at the Flp-bound FRT site. Levels of Ubx5-TAP were monitored by ChIP and qPCR following formaldehyde crosslinking in cells grown as described in (C). The graph shows enrichment of qPCR signals over the unrelated intergenic region. Data are presented as means ± SDs for n = 5 independent biological replicates. p-values for +200 bp were defined by 2-way ANOVA using Tukey's multiple comparisons test (n.s., non-significant; *p < 0.05; ** p < 0.01; **** p < 0.0001). In addition to the indicated mutations, all strains are bar1∆ Ubx5-TAP. No FRT strain and raffinose (raf) samples were used as negative controls.",
    "ncbi_link": "TAP: 
bar1: 854797
Ubx5: 851930"
  },
  {
    "caption": "Cdc48 occupancy at the Flp-bound FRT site. Levels of Cdc48-TAP were monitored by ChIP and qPCR following formaldehyde crosslinking in asynchronous cells before and after Flp-cc induction with galactose. The graph shows enrichment of qPCR signal over the unrelated intergenic region. Data are presented as means ± SDs of 3 to 4 independent biological replicates. p-values for +200 bp were defined by 2‑way ANOVA using Tukey's multiple comparisons test (n.s., non-significant; **** p < 0.0001). In addition to the indicated mutations, all strains are Cdc48-TAP. No FRT strain was used as a negative control.",
    "ncbi_link": "TAP: 
Cdc48: 851431"
  },
  {
    "caption": "Ubiquitination of the FRT locus. Asynchronous cultures were grown in 2% raffinose (raf) or additionally supplemented with 3% galactose (gal) to induce flp-H305L expression. Cells were also collected during glucose repression of flp-H305L expression at time points 30 min (glu 30') and 120 min (glu 120'). Ubiquitin antibody was used for ChIP-qPCR analysis following formaldehyde crosslinking. Data are shown as the mean ± SDs of three to six independent replicates. p-values for +200 bp were defined by 2‑way ANOVA using Tukey's multiple comparisons test (n.s., non-significant; *p < 0.05; *** p < 0.001; **** p < 0.0001). In addition to all indicated mutations, all strains are bar1∆ Ddi1-TAP.",
    "ncbi_link": "TAP: 
bar1: 854797
Ddi1: 856886"
  },
  {
    "caption": "ubx5∆ restores wss1∆ resistance to HU and FA but not upon additional deletion of DDI1. Strains were grown in YEPD and either treated with 40 mM FA for 15 min or directly spotted on plates containing 100 mM of HU or 5 μg/mL CPT. Plates were incubated for 2 days at 30°C.",
    "ncbi_link": "DDI1: 856886
ubx5: 851930
wss1: 856536"
  },
  {
    "caption": "Endogenous HA-Ddi1 levels are still elevated upon additional ubx5∆ mutation. Levels in total cell extracts were compared by immunoblotting. For quantification, anti-HA signal was normalized to Pgk1 and then normalized to WT (see (D)). Quantification of HA-Ddi1 levels shown in (C). The anti-HA signal was compared to Pgk1 and normalized to WT. Quantifications of 5 biological replicates are presented as means ± SDs. Significance was defined by ordinary one-way ANOVA using Dunnett's multiple comparisons test and WT as a control (*p < 0.05; ** p < 0.01).",
    "ncbi_link": "ubx5: 851930"
  },
  {
    "caption": "Catalytic activity of the protease Ddi1 is essential for survival of the ubx5∆ wss1∆ yeast mutant. Mutants carrying wild-type (WT) Ddi1, D220A catalytic mutant or ddi1∆ in combination with ubx5∆, wss1∆ or double ubx5∆ wss1∆ were grown in YEPD. Cells were treated with 40 mM formaldehyde (FA) for 15 min or directly spotted on plates supplemented with 100 mM hydroxyurea (HU). Plates were incubated for 2 days at 30°C.",
    "ncbi_link": "ddi1: 856886
Ddi1: 856886
ubx5: 851930
wss1: 856536"
  },
  {
    "caption": "Ubx5 loss restores HU-induced Rpb1 degradation in wss1∆ and requires Ddi1. Rpb1 levels were defined in cells growing in the presence of 200 mM HU and 100 μg/mL cycloheximide (CHX) at the indicated time points. Rpb1 and Pgk1 levels in total cell extracts were probed by immunoblotting and quantified using fluorescent secondary antibodies. See (B) for quantifications. Images show immunoblotting using chemiluminescence.",
    "ncbi_link": "Ddi1: 856886
Ubx5: 851930
wss1: 856536"
  },
  {
    "caption": " A. Expression heat map of netrin-3 and netrin-1. Receptors of netrin-1 and putative receptors of netrin-3: DCC, UNC5-A, -B, -C, -D, Neogenin, APP, CD146 are presented. The color legend (right-hand side) describes all tumor types included in the heat map. Asterisks indicate the two main pathologies in which netrin-3 expression is detectable. C. Percentage of cell lines positive for netrin-1 and/or -3 expression. Co-occurrence of expression was calculated using Fisher's exact test. P-value is indicated in the table. ",
    "ncbi_link": "APP: 351
DCC: 1630
CD146: 4162
Neogenin: 4756
netrin-1: 9423
netrin-3: 4917
UNC5-A: 90249"
  },
  {
    "caption": " B. Analysis of netrin-1 and -3 expression in tumor cell lines and ranked according to netrin-1 expression ",
    "ncbi_link": "netrin-1: 9423"
  },
  {
    "caption": " A. Quantification of netrin-3 gene expression by q-RT-PCR in a panel of 181 human NB stages 1, 2, 3, 4 and 4S. Number of cases is indicated on the graph. Error bars indicate s.e.m. Statistical treatment of the data was performed using a two-sided Student t-test. ",
    "ncbi_link": "netrin-3: 4917"
  },
  {
    "caption": " B. Quantification of netrin-3 gene expression by q-RT-PCR in a panel of 181 human neuroblastoma patients, defined as low- and high-risk NB. The number of cases is indicated on the graph. Error bars indicate s.e.m. Statistical treatment of the data was performed using a two-sided Student t-test. ",
    "ncbi_link": "netrin-3: 4917"
  },
  {
    "caption": " C. Netrin-3 high expression is a marker of poor prognosis in NB. 280 months overall Kaplan-Meier survival curves in a panel of 181 patients of all NB stages. The cohort was dichotomized base on netrin-3 median expression (in green and red). Statistical treatment of the data: Mantel-Cox; p value is indicated below the graph. ",
    "ncbi_link": "netrin-3: 4917
Netrin-3: 4917"
  },
  {
    "caption": " D. Netrin-3 high expression is a marker of poor prognosis in aggressive NB. 280 months overall Kaplan-Meier survival curves in a panel of 54 stage 4 patients. The cohort was dichotomized base on netrin-3 expression, as presented in panel C. Statistical treatment of the data: Mantel-Cox; p-value is indicated below the graph. E. Confirmation in 498 RNA-seq NB patients that netrin-3 high expression is a marker of poor prognosis in NB. 6,000 days overall Kaplan-Meier survival curves. The cohort was dichotomized based on netrin-3 median expression (in green and red). Statistical treatment of the data: Mantel-Cox; p-value is indicated below the graph.",
    "ncbi_link": "netrin-3: 4917
Netrin-3: 4917"
  },
  {
    "caption": " A. Gene Set Enrichment Analysis (GSEA) in high netrin-3 NB patients. The cohort was dichotomized with the n=50 lowest vs 50 highest: amplification the MYCN pathway (p=0.039; fdqr=0.025). ",
    "ncbi_link": "MYCN: 4613
netrin-3: 4917"
  },
  {
    "caption": " B. Netrin-3 expression is higher in MYCN amplified NB patients. The cohort was dichotomized based on mycn amplification and sorted for netrin-3 expression. Statistical treatment of the data: Welsh test; p-value is indicated on the graph. Error bars indicate s.e.m (boxes= 25th to 75th percentile; central band= mean; whiskers = min to max).",
    "ncbi_link": "MYCN: 4613
mycn: 4613
netrin-3: 4917
Netrin-3: 4917"
  },
  {
    "caption": " C. Q-RT-PCR analysis of netrin-3 gene expression in IMR32 (n=5) and IGRN91 (n=5) NB cell lines after MYCN silencing by siRNA (U-test). Error bars indicate s.e.m. ",
    "ncbi_link": "MYCN: 4613
netrin-3: 4917"
  },
  {
    "caption": " D. ChIP-seq analysis of MYCN binding, active enhancer epigenetic marks H3K27ac, H3K4me1, and active promoter epigenetic mark H3K4me3, on netrin-3 locus (red line). An enrichment of MYCN, associated with active enhancer marks, was detected in three different neuroblastoma cell lines NB-1643, COGN415 and LAN5. ",
    "ncbi_link": "MYCN: 4613
netrin-3: 4917"
  },
  {
    "caption": " E. Quantitative analysis showing the size of IGRN91 primary tumors implanted on CAM and silenced or not for netrin-3 (n=11 siScr, n=9 siNetrin-3; U-test). Error bars indicate s.e.m. F. Quantitative analysis showing the size of IMR32 primary tumors silenced or not for netrin-3 (n=5 siScr, n=7 siNetrin-3; U-test). Error bars indicate s.e.m. ",
    "ncbi_link": "netrin-3: 4917
Netrin-3: 4917"
  },
  {
    "caption": " A. Deep analysis of netrin-3 gene expression in lung cancer cell lines (n=76; RNA-Seq). ",
    "ncbi_link": "netrin-3: 4917"
  },
  {
    "caption": " B. Q-RT-PCR analysis of netrin-1 and -3 expression, in lung cancer cell Lines (Error bars indicate SD, n=3). ",
    "ncbi_link": "netrin-1: 9423"
  },
  {
    "caption": "  C. Representative netrin-3 and -1 mRNA detection, using RNAscope on SCLC paraffin embedded tumor sections. Negative control DAPB, positive control PPiB. Each brown dot is a unique molecule of mRNA of each targeted gene (n=10, scale bars 20µm). D. Quantification of netrin-3 and -1 expression in human SCLC paraffin embedded tumor sections (High≥ 50% marked cells; Low≤ 5%).  ",
    "ncbi_link": "DAPB: 
netrin-3: 4917
PPiB: 5479"
  },
  {
    "caption": " A. ChIP-seq analysis of NeuroD1 and ASCL-1 binding on the netrin-3 gene promoter. A major binding site was detected (red and blue peaks for NeuroD1 and ASCL1 respectively). Input controls are shown below (black). ",
    "ncbi_link": "netrin-3: 4917"
  },
  {
    "caption": " B. ChIP-seq analysis of NeuroD1 and ASCL-1 chromatin enrichment, which was associated with broad H3K27ac-enriched regions at the netrin-3 locus (red line), indicating a transcriptionally active region in SCLC cell lines. (rep= experimental replicates). ",
    "ncbi_link": "netrin-3: 4917"
  },
  {
    "caption": " C. Q-RT-PCR analysis of netrin-3 gene expression in NCI-H82 (n=6) and NCI-H69 (n=4) SCLC cell lines after Neurod-1 and ASCL-1 silencing by siRNAs (U-test). Error bars indicate s.e.m. ",
    "ncbi_link": "ASCL-1: 429
Neurod-1: 4760
netrin-3: 4917"
  },
  {
    "caption": " D. Netrin-3 silencing delays or inhibits SCLC engraftment in vivo. NMRI nude mice were subcutaneously engrafted with either NCI-H82-CRIPSR/cas9-NTN3 with three different guides RNAs (sG1 p=0.0022; sG2 p≤0.001; and sG3 p≤0.001) or control cells (sGc) n=6/group. Positive tumor engraftment was report when tumors reached 50 mm3 (Mantel Cox). ",
    "ncbi_link": "Netrin-3: 4917
NTN3: 4917"
  },
  {
    "caption": " F. NCI-H69-CRISPR/Cas9 cells presented in E. were subcutaneously engrafted with either NCI-H69- CRIPSR/cas9-NTN3 with three different guide RNAs (sG1 p=0.017; sG2 p=0.028; and sG3 p=0.001) or control cells (sGc) n=6/group. Positive tumor engraftment was report when tumors reached 20 mm3 (Mantel Cox). ",
    "ncbi_link": "NTN3: 4917"
  },
  {
    "caption": " B. Analysis of NP137 binding on netrin-2L, netrin-1; netrin-4 or netrin-G2 by bio-layer interferometry assays. Kd rhNTN1: 0.96 ± 0.30nM; Kd for rchNTN2: 1.53 ± 0.96nM ",
    "ncbi_link": "NTN1: 9423
NTN2: 4917"
  },
  {
    "caption": "A, B In-gel kinase assay of OST1 activity in ABA receptor mutants under cold stress. Ten-day-old wild type, ost1-3, pyr1 pyl1,4, pyr1 pyl1,2,4, pyr1 pyl4,5,8 and pyr1 pyl1,4,5,8 mutants were treated at 4°C for 2 h. Total protein extracts were prepared and separated on SDS-PAGE gel containing 0.1 mg/mL GST-∆ABF2 as a substrate, and incubated with 60 μCi of [γ-32P]ATP. Representative pictures are shown in (A) and relative kinase activity is shown in (B). Data information: In (A , Top, gel autoradiograph; bottom, Coomassie Brilliant Blue (CBB) staining of RuBisCO large subunit was used as a loading control. The ratio of band intensity of OST1 to RuBisCO in the wild type with cold treatment for 2 h was set to 1.00. In (B , each bar represents the mean ± SEM of three biological repeats. *P < 0.05 (two-tailed t-test).",
    "ncbi_link": "ost1: 829541
pyl1: 834722
pyl4: 818411
pyr1: 827510"
  },
  {
    "caption": "C, D In-gel kinase assay of OST1 activity in ABI1-OE14 and abi1 abi2 hab1 mutants under cold stress. Representative pictures are shown in (C) and relative kinase activity is shown in (D). Data information: In C), Top, gel autoradiograph; bottom, Coomassie Brilliant Blue (CBB) staining of RuBisCO large subunit was used as a loading control. The ratio of band intensity of OST1 to RuBisCO in the wild type with cold treatment for 2 h was set to 1.00. In D), each bar represents the mean ± SEM of three biological repeats. *P < 0.05 (two-tailed t-test).",
    "ncbi_link": "ABI1: 828714
abi1: 828714
abi2: 835809
hab1: 843609"
  },
  {
    "caption": "C Co-IP assay of OST1 with EGR2 in vivo. 35S:HF-OST1/Super:EGR2-Myc or 35S:HF-OST1/Super:Myc was expressed in N. benthamiana leaves. Total proteins were immunoprecipitated with anti-Myc agarose beads, and the co-immunoprecipitation products were subjected to immunoblot analysis. EGR2-Myc and HF-OST1 were detected with anti-Myc and anti-HA antibodies, respectively.",
    "ncbi_link": "Myc: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "D Bimolecular fluorescence complementation (BiFC) assay. Wild-type Arabidopsis protoplasts transformed with OST1-YFPC and EGR2-YFPN proteins were incubated for 18 h. The interaction signal was detected by confocal microcopy. The combinations of OST1-YFPC/GUS-YFPN and GUS-YFPC/EGR2-YFPN were used as negative controls. Scale bars: 100 μm.",
    "ncbi_link": "YFP: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "F, G In-gel assay of OST1 activity in 10-d-old wild type, egr1 and egr2 single mutants, and the egr1 egr2 double mutant under cold stress. Data information: the ratio of band intensity of OST1 to RuBisCO in the wild type with cold treatment for 2 h was set to 1.00. In (F representative pictures are shown: Top, autoradiograph; bottom, CBB staining. In (G relative kinase activity is shown. Each bar represents the mean ± SEM of three biological repeats. **P < 0.01 (two-tailed t-test).",
    "ncbi_link": "egr1: 819731
egr2: 832860"
  },
  {
    "caption": "H, I In-gel assay of OST1 activity in 10-d-old wild-type and EGR2-overexpressing plants under cold stress. Data information the ratio of band intensity of OST1 to RuBisCO in the wild type with cold treatment for 2 h was set to 1.00. In H), representative pictures are shown: Top, autoradiograph; bottom, CBB staining. In I), relative kinase activity is shown. Each bar represents the mean ± SEM of three biological repeats. **P < 0.01 (two-tailed t-test).",
    "ncbi_link": "EGR2: 832860"
  },
  {
    "caption": "Freezing phenotype (A) of the egr2-3 mutant and egr2/EGR2:EGR2-Myc complementation lines under non-acclimated (NA) and acclimated (CA; 4 d at 4°C) conditions. Two-week-old seedlings grown on MS medium containing 0.8% agar were treated at −5°C for 0.5 h (NA) or −8°C for 0.5 h (CA).",
    "ncbi_link": "Myc: 
egr2: 832860
EGR2: 832860"
  },
  {
    "caption": "survival rate (B) of the egr2-3 mutant and egr2/EGR2:EGR2-Myc complementation lines under non-acclimated (NA) and acclimated (CA; 4 d at 4°C) conditions. Two-week-old seedlings grown on MS medium containing 0.8% agar were treated at −5°C for 0.5 h (NA) or −8°C for 0.5 h (CA). Data information each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
egr2: 832860
EGR2: 832860"
  },
  {
    "caption": "ion leakage (C) of the egr2-3 mutant and egr2/EGR2:EGR2-Myc complementation lines under non-acclimated (NA) and acclimated (CA; 4 d at 4°C) conditions. Two-week-old seedlings grown on MS medium containing 0.8% agar were treated at −5°C for 0.5 h (NA) or −8°C for 0.5 h (CA). Data information each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
egr2: 832860
EGR2: 832860"
  },
  {
    "caption": "Freezing phenotype of EGR2-overexpressing plants. Two-week-old Super:EGR2-Myc plants",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "survival rate (E) of EGR2-overexpressing plants. Two-week-old Super:EGR2-Myc plants Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "ion leakage (F) of EGR2-overexpressing plants. Two-week-old Super:EGR2-Myc plants Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "Expression of CBFs (G in egr2-3 mutant plants. Two-week-old seedlings were treated at 4°C for the indicated period and subjected to qRT-PCR analysis. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "egr2: 832860"
  },
  {
    "caption": "Expression of CBFs target genes (H in egr2-3 mutant plants. Two-week-old seedlings were treated at 4°C for the indicated period and subjected to qRT-PCR analysis. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "egr2: 832860"
  },
  {
    "caption": "Expression of CBFs in EGR2-overexpressing plants. Two-week-old seedlings were treated at 4°C for the indicated period and subjected to qRT-PCR analysis. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "EGR2: 832860"
  },
  {
    "caption": "Expression of CBFs target genes J) in EGR2-overexpressing plants. Two-week-old seedlings were treated at 4°C for the indicated period and subjected to qRT-PCR analysis. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "EGR2: 832860"
  },
  {
    "caption": "N-myristoylation of EGR2 and EGR2G2A in N. benthamiana leaves. Protein extracts prepared from N. benthamiana leaves expressing EGR2-Myc or EGR2G2A-Myc were immunoprecipated by anti-Myc agarose beads. Precipitated proteins were detected by anti-Myc and anti-myristic acid antibodies.",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "E N-myristoylation of EGR2 in plants. Total proteins were prepared from two-week-old EGR2-Myc seedlings The products were immunoprecipated by anti-Myc agarose beads and detected by anti-streptavidin-HRP antibody. EGR2-Myc detected by anti-Myc antibody was used as a loading control.",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "F Immunoblot assay of myristoylated EGR2 under cold stress. Total proteins were prepared form EGR2-Myc plants treated with 4°C for the indicated period, and immunoprecipated by anti-Myc agarose beads. Precipitated proteins were detected by anti-Myc and anti-myristic acid antibodies. The ratio of band intensity detected by anti-myristic acid antibody to anti-Myc antibody without cold treatment was set to 1.00. Representative pictures are shown (left) and quantitative analysis is shown (right). Each bar represents the mean ± SEM of three biological repeats. **P < 0.01 (two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860"
  },
  {
    "caption": "G Expression of EGR2 in egr2-3 EGR2:EGR2G2A-Myc complementation transgenic plants. Total RNAs were extracted from 2-week-old seedlings and subjected to RT-PCR analysis. EF1α was used as a loading control.",
    "ncbi_link": "EF1α: 
Myc: 
EGR2: 832860
egr2: 832860"
  },
  {
    "caption": "Freezing tolerance assays of the egr2-3 mutant and EGR2:EGR2G2A-Myc transgenic plants in egr2-3 mutant. Two-week-old seedlings grown on MS medium containing 0.8% agar at 22°C were treated at −5°C for 0-1.5 h (NA) or −8°C for 0-1.5 h (CA). Representative photographs (-5oC, 0.5 h; -8oC, 0.5 h) are shown in (H)",
    "ncbi_link": "Myc: 
egr2: 832860
EGR2: 832860"
  },
  {
    "caption": "Freezing tolerance assays of the egr2-3 mutant and EGR2:EGR2G2A-Myc transgenic plants in egr2-3 mutant. Two-week-old seedlings grown on MS medium containing 0.8% agar at 22°C were treated at −5°C for 0-1.5 h (NA) or −8°C for 0-1.5 h (CA). survival rate is shown in (I). Data shown in (I) are mean values ± SEM of three biological replicates, each of which has three technical replicates. Asterisks indicate significant differences compared with wild type for the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test); n. s., not significant.",
    "ncbi_link": "Myc: 
egr2: 832860
EGR2: 832860"
  },
  {
    "caption": "C, D Effect of cold stress on the interaction of EGR2 and NMT1 determined by co-IP assay. Arabidopsis protoplasts expressing HF/NMT1-Myc and HF-EGR2/NMT1-Myc were treated with or without 4°C for 2 h. Total proteins were immunoprecipated by anti-HA agarose beads. Anti-Myc and anti-HA were used to detect NMT1-Myc and HF-EGR2, respectively. In (C), relative band intensity is shown below the co-IP blot. In (D), each bar represents the mean ± SEM of three biological experiments (**P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860
NMT1: 835805"
  },
  {
    "caption": "F Expression of NMT1 in NMT1-Myc overexpression plants. EF1α was used as a loading control.",
    "ncbi_link": "Myc: 
NMT1: 835805"
  },
  {
    "caption": "Freezing phenotype (G) of NMT1-Myc overexpression transgenic plants. Two-week-old Super:NMT1-Myc plants were treated at −5°C (NA) or −8°C for 0.5 h (CA).",
    "ncbi_link": "Myc: 
NMT1: 835805"
  },
  {
    "caption": "survival rate (H) of NMT1-Myc overexpression transgenic plants. Two-week-old Super:NMT1-Myc plants were treated at −5°C (NA) or −8°C for 0.5 h (CA). In (H), each bar represents the mean ± SEM of three biological experiments, and asterisks indicate significant differences compared with the wild type for the same treatment (*P < 0.05, two tailed t-test).",
    "ncbi_link": "Myc: 
NMT1: 835805"
  },
  {
    "caption": "OST1 kinase activity in NMT1-Myc overexpression plants under cold stress. Top, autoradiograph; bottom, CBB staining. Representative pictures are shown in (I) In (I): the ratio of band intensity of OST1 to RuBisCO in wild type with cold treatment for 2 h was set to 1.00.",
    "ncbi_link": "Myc: 
NMT1: 835805"
  },
  {
    "caption": "OST1 kinase activity in NMT1-Myc overexpression plants under cold stress. the relative kinase activity is shown in (J). In (J): each bar represents the mean ± SEM of three independent experiments (**P < 0.01, two tailed t-test).",
    "ncbi_link": "Myc: 
NMT1: 835805"
  },
  {
    "caption": "A, B Pull-down assay. Total proteins prepared from EGR2-Myc or EGR2G2A-Myc transgenic plants was immunoprecipated with anti-Myc agarose beads, and then incubated with GST-OST1. Anti-Myc and anti-GST antibody were used to detect GST-OST1 and EGE2-Myc. Representative pictures are shown in (A). Relative interaction is shown in (B). Data information: In (A Relative band intensities are shown. In (B each bar represents the mean ± SEM of three independent experiments (**P < 0.01, two-tailed t-test).",
    "ncbi_link": "EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "C LCI of EGR2 and EGR2G2A with OST1 in N. benthamiana leaves. EGR2-cLuc/OST1-nLuc and EGR2G2A-cLuc/OST1-nLuc were expressed in N. benthamiana leaves for 48 h. EGR2-cLuc/nLuc, EGR2G2A-cLuc/nLuc, and cLuc/OST1-nLuc were used as negative controls. Scale bar: 2 cm.",
    "ncbi_link": "Luc: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "D, E Co-IP assay. EGR2-Myc/HF-OST1, EGR2G2A-Myc/HF-OST1, HF/EGR2-Myc and HF/EGR2G2A-Myc were expressed in N. benthamiana leaves. Total proteins were immunoprecipated by anti-HA agarose beads. Anti-HA and anti-Myc antibodies were used to detect HF-OST1, EGR2-Myc and EGR2G2A-Myc, respectively. Representative pictures are shown in (D), and relative interaction is shown in (E). Data information: In : Relative band intensities are shown. In each bar represents the mean ± SEM of three independent experiments (**P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "F, G Effect of EGR2G2A on the interaction of OST1 and EGR2 in Arabidopsis protoplasts expressing HF-OST1/EGR2-GFP/EGR2-Myc, HF-OST1/EGR2-GFP/EGR2G2A-Myc, or HF-OST1/EGR2-GFP. Total proteins were immunoprecipated by anti-HA agarose beads. Anti-Myc, anti-GFP, and anti-HA antibodies were used to detect EGR2-Myc, EGR2-GFP, and HF-OST1, respectively. Representative pictures are shown in (F), and relative interaction is shown in (G). Data information In Relative band intensities are shown. In each bar represents the mean ± SEM of three independent experiments (**P < 0.01, two-tailed t-test).",
    "ncbi_link": "GFP: 
Myc: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "H, I Effect of cold stress on the interaction of OST1 and EGR2. Arabidopsis protoplasts expressing EGR2-Myc/HF-OST1 and EGR2-Myc/HF were treated at 4°C for 0 and 2 h. Total proteins were immunoprecipated by anti-HA agarose beads. The co-immunoprecipitated products were detected by anti-HA and anti-Myc antibodies, respectively. Representative pictures are shown in (H), and relative interaction is shown in (I). Data information: In H) Relative band intensities are shown. In I): each bar represents the mean ± SEM of three independent experiments (**P < 0.01, two-tailed t-test).",
    "ncbi_link": "Myc: 
EGR2: 832860
OST1: 829541"
  },
  {
    "caption": "Freezing phenotype (A) of wild type, ost1-3, egr2-3, and ost1 egr2 mutants. Two-week-old seedlings grown on MS medium were treated at −5°C (NA) or −8°C for 0.5 h (CA).",
    "ncbi_link": "egr2: 832860
ost1 : 829541
ost1: 829541"
  },
  {
    "caption": "survival rate and ion leakage (B) of wild type, ost1-3, egr2-3, and ost1 egr2 mutants. Two-week-old seedlings grown on MS medium were treated at −5°C (NA) or −8°C for 0.5 h (CA). Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "egr2: 832860
ost1: 829541"
  },
  {
    "caption": "C Expression of CBFs in wild type, ost1-3, egr2-3, and ost1 egr2-3 plants under cold stress. Two-week-old seedlings grown at 22°C were treated at 4°C for 0 h and 3 h. Data information: each bar represents the mean ± SEM of three independent experiments, each of which has three technical repeats. Asterisks indicate significant differences compared to the wild type with the same treatment (*P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "egr2: 832860
ost1: 829541"
  },
  {
    "caption": "(a) FLAG-AMBRA1 was transfected into HEK293 cells together with ULK1WT or ULK1K46I Myc-tagged proteins. Protein extracts were immunoprecipitated (IP) using anti-FLAG antibody.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(d,e) ULK1 and AMBRA1 constructs are illustrated. Asterisks mark nonspecific bands corresponding to immunoglobulins. (d) HEK293 cells were co-transfected with vectors encoding AMBRA1 together with ULK1-Myc FL (full length) or its deletion mutants encoding the kinase and the proline-rich domains (Δ829-1,051), and the ULK1 carboxy-terminal domain (Δ1-828). Protein extracts were immunoprecipitated using anti-Myc antibody.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(d,e) ULK1 and AMBRA1 constructs are illustrated. Asterisks mark nonspecific bands corresponding to immunoglobulins. (e) HEK293 cells were co-transfected with vectors encoding ULK1-HA together with β-galactosidase-Myc (βgal), AMBRA1 full-length (FL), and F1, F2 or F3 Myc-tagged proteins. Protein extracts were immunoprecipitated using anti-HA antibody. The relative amounts of co-immunoprecipitatedULK1 and F1 or F3, respectively, are the same (see upper and lower left panel).",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(g) HEK293 cells were transfected with scramble siRNA or ATG13 siRNA. Protein extracts were immunoprecipitated using ULK1 antibody or IgG. The band density ratio of immunoprecipitated AMBRA1 relative to immunoprecipitated ULK1 is analysed, with the control ratio arbitrarily defined as 1.00. n = 3 extracts prepared from independent experiments; data are presented as means±s.d. and significance is P = 0.04. Uncropped images of blots/gels are shown in Supplementary Fig. S6. Source data of statistical analysis are shown in Supplementary Table S1.",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "(a) HEK293 cells were transfected with AMBRA1 or the empty vector, as a control. ULK1, AMBRA1 and actin were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(b) Protein extracts from wild-type (Ambra1+/+) and homozygous (Ambra1gt/gt) embryos for the Ambra1 gene-trap mutation at developmental day 14.5 were analysed by western blotting using anti-Ulk1 or anti-Hsp90 (loading control) antibodies. Quantification is shown on the right. n = 6 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.037.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "(c) AMBRA1, ULK1 and actin (as a protein loading control) were analysed by western blotting in HeLa cells transiently transfected with scramble siRNA or AMBRA1 siRNA. Quantification is shown on the right. n = 5 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.007.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(d) HeLa cells stably interfered for AMBRA1 were transiently transfected with empty vector or AMBRA1 vector; AMBRA1, ULK1, ATG13, p-ATG13 and actin levels were analysed by western blotting. Quantification of ULK1 and pATG13 bands is shown on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.006 for ULK1 and P = 0.044 and P = 0.011 for pATG13.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(e) HeLa cells were transfected or not with vector encoding AMBRA1 and treated with 35 μM cycloheximide (CHX) for 6 and 8 h before extraction. ULK1, actin and AMBRA1 were analysed by western blotting. Quantification is shown below. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.049 and P = 0.02.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(c) In HeLa cells, AMBRA1 was downregulated by RNAi. Protein extracts were immunoprecipitated using anti-ULK1 antibody or with IgG as a negative control. Purified complexes and total extracts were analysed by western blotting using anti-ULK1, anti-Lys-63 ubiquitin and anti-AMBRA1 antibodies. Of note, ULK1 levels in the co-immunoprecipitation experiment do not change in this case in the AMBRA1 siRNA lane, owing to saturation of the anti-ULK1 antibody (see also Fig. 4h).",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(d) HeLa cells were co-transfected with vectors encoding for ubiquitin Lys-63-HA alone or in combination with AMBRA1. Protein extracts were immunoprecipitated using an anti-ULK1 antibody or with IgG as a negative control and Ub-Lys-63-HA, ULK1 and AMBRA1 were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "(a) HeLa cells were transfected with FLAG-TRAF6 or grown in starvation medium for 1 h. Some of them were treated with chloroquine. LC3, p62 and actin were analysed by western blotting. Quantification of LC3II and p62 bands is shown on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.017 for LC3 and P = 0.01 and P = 0.04 for p62.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "(b) HeLa cells were transduced with AMBRA1 lentiviral shRNA and transfected or not with FLAG-TRAF6. Quantification of LC3II and p62 bands is shown on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.001 and P = 0.0018 for LC3 and P = 0.004 for p62.",
    "ncbi_link": "AMBRA1: 55626
TRAF6: 7189"
  },
  {
    "caption": "(f) In HeLa cells, TRAF6 was downregulated by RNAi. AMBRA1, ULK1, TRAF6, ATG13 and actin were analysed by western blotting.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "(h) HeLa cells stably interfered for AMBRA1 were transfected with FLAG-TRAF6 and Ub-Lys-63-HA as indicated. Protein extracts were immunoprecipitated using anti-ULK1 antibody.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(a-c) Two canonical TRAF6-binding sites in AMBRA1 are essential for its interaction with TRAF6. HEK293 cells were co-transfected with vectors encoding FLAG-TRAF6 together with AMBRA1WT and mutant constructs. Protein extracts were immunoprecipitated using an anti-FLAG antibody. AMBRA1 and FLAG-TRAF6 were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(a-c) Two canonical TRAF6-binding sites in AMBRA1 are essential for its interaction with TRAF6. HEK293 cells were co-transfected with vectors encoding FLAG-TRAF6 together with AMBRA1WT and mutant constructs. Protein extracts were immunoprecipitated using an anti-FLAG antibody. AMBRA1 and FLAG-TRAF6 were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626
TRAF6: 7189"
  },
  {
    "caption": "(d) HeLa cells were transfected with AMBRA1 RNAi oligonucleotide (siRNA AMBRA1). Then, cells were co-transfected with vectors encoding ubiquitin-HA and AMBRA1WT or AMBRA1AA, respectively. Protein extracts were immunoprecipitated using anti-ULK1 antibody; ubiquitin-HA, ULK1 and AMBRA1 were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(e) HeLa cells stably interfered for AMBRA1 were transduced with lentiviral vectors encoding β-galactosidase (negative control) AMBRA1WT or AMBRA1AA respectively; protein extracts were analysed by western blotting using anti-ULK1, anti-AMBRA1 anti-ATG13, anti-pATG13 and anti-actin antibodies.",
    "ncbi_link": "β-galactosidase: 
AMBRA1: 55626"
  },
  {
    "caption": "(g) GFP-LC3 MEF cells from wild-type (Ambra1+/+) and homozygous (Ambra1gt/gt) embryos were transduced with the indicated lentiviral vectors and quantification of LC3 puncta per cells is shown on the right. Bars represent mean±s.e.m. of triplicate samples with 50 cells analysed per sample; n = 3 independent experiments. Significance is P = 0.001 and P = 0.003 (n = 3). Scale bar, 10 μm.",
    "ncbi_link": "Ambra1: 228361"
  },
  {
    "caption": "(b) HEK293 cells were transfected with TRAF6 RNAi oligonucleotide (TRAF6 siRNA) or unrelated oligonucleotides as a control (Ctrl siRNA). Then, cells were co-transfected with vectors encoding ULK1-HA and ULK1-Myc and protein complexes were immunoprecipitated using anti-Myc antibody. Protein extracts were analysed by western blotting using anti-HA, anti-Myc and anti-TRAF6 antibodies. Quantification of ULK1-HA relative to ULK1-Myc is reported on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.037.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "(c) HEK293 cells were transfected with AMBRA1 RNAi oligonucleotide (AMBRA1 siRNA) or unrelated oligonucleotides as a control (Ctrl siRNA). Then, cells were co-transfected and analysed as in a. Quantification is shown on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.044.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(d) HEK293 cells were co-transfected with vectors encoding for ULK1-HA, ULK1-Myc and AMBRA1WT or AMBRA1AA respectively. Protein complexes were immunoprecipitated and analysed as in a. Quantification is shown on the right. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.014.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(a) Highly purified mTOR was incubated with radiolabelled ATP without substrate, with purified FLAG-AMBRA1 and purified FLAG-AMBRA1S52A and analysed by autoradiography. The lower panels show a FLAG and mTOR western blot (WB).",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(d) HeLa cells stably interfered for AMBRA1 were transduced with the indicated lentiviral vectors encoding for β-galactosidase, AMBRA1WT or AMBRA1S52A respectively and some of them were treated with chloroquine for 1 h. Protein extracts were analysed by western blotting using anti-LC3, anti-p62 and anti-actin antibodies. Quantification of LC3II and p62 bands is shown below. n = 3 extracts prepared from independent experiments. Data are presented as means±s.d. and significance is P = 0.038.",
    "ncbi_link": "β-galactosidase: 
AMBRA1: 55626"
  },
  {
    "caption": "(e) GFP-LC3 MEF cells from wild-type (Ambra1+/+) and homozygous (Ambra1gt/gt) embryos were transduced with indicated lentiviral vectors and quantification of LC3 puncta per cell is shown on the right. Bars represent mean±s.e.m. of triplicate samples and 50 cells analysed per sample. n = 3 independent experiments. Significance is P = 0.001 and P = 0.003. Scale bar, 10 μm",
    "ncbi_link": "Ambra1: 228361
LC3: 67443///66734"
  },
  {
    "caption": "(f) HeLa cells stably interfered for AMBRA1 were co-transfected with vectors encoding Ub-Lys-63-HA and AMBRA1WT or AMBRA1S52A, respectively. Protein extracts were immunoprecipitated using an anti-ULK1 antibody and ubiquitin Lys-63-HA, ULK1, AMBRA1 and actin were analysed by western blotting.",
    "ncbi_link": "AMBRA1: 55626
Ub: 7314///6233///7311///7316"
  },
  {
    "caption": "(g) HeLa cells stably interfered for AMBRA1 were transduced as in d; protein extracts were analysed by western blotting using anti-AMBRA1, anti-ATG13, anti-pATG13 and anti-actin antibodies. Quantification of the p-ATG13 band is shown below.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "(h) HeLa cells transfected with ULK1-HA, ULK1-Myc and different AMBRA1 constructs, respectively. Protein complexes were immunoprecipitated using anti-HA antibody and analysed by western blotting using anti-HA, anti-Myc and anti-AMBRA1 antibodies.",
    "ncbi_link": "AMBRA1: 55626"
  },
  {
    "caption": "B. Growth of DiCre-3D7 transgenic lines following LDH1, HAD4, and  Lipin depletion with 100 nM  rapamycin and 2.5 mM  glucosamine was assessed relative to uninduced parasite cultures. The untransfected DiCre-3D7 parasite line was used as a negative control. Data are presented as the mean ± standard error of the mean (SEM) from three independent replicates.",
    "ncbi_link": "DiCre: 2777477
Lipin: 814349
HAD4: 810737
LDH1: 814115"
  },
  {
    "caption": "C. Untargeted   LC-MS analysis of LDH1 depletion (one cycle of rapamycin and glucosamine treatment) indicated minimal but selective metabolic changes. m/z feature intensities are plotted as the log2 ratio of treated/untreated and the Benjamini-Hochberg corrected P values across six biological replicates plotted as -log10(P). Below,  LDH1 substrate and product (pyruvate and lactate respectively) abundance plotted as the ratio of treated/untreated from biological replicates (mean±SEM) and the parental DiCre line presented as the negative control.",
    "ncbi_link": "DiCre: 2777477
LDH1: 814115"
  },
  {
    "caption": "D. Loss of Lipin (PF3D7_0303200) leads to accumulation of various lipid species (three cycles of  rapamycin and glucosamine treatment). Data are presented as the mean log2 fold change  Lipin depleted (treated) enriched trophozoite-stage  iRBCs to untreated controls from three to six biological replicates (± SD). The schematic depicts the proposed  lipid phosphatase activity of Lipin.",
    "ncbi_link": "Lipin: 814349"
  },
  {
    "caption": "E. Loss of HAD4 leads to increases in intracellular levels of several nucleotides and intermediates in lower glycolysis. Data are represented as the mean log2 fold change of enriched trophozoite-stage iRBCs treated for three cycles compared to untreated controls from three/four biological replicates. Three nucleotide-nucleoside pairs are depicted in the top inset panels, HAD4 disruption leads to accumulation of the nucleotide-monophosphate and depletion of the  nucleoside. The schematic depicts lower glycolysis and triose-phosphate interconversion, with the corresponding  metabolite levels following HAD4 disruption depicted in the lower right inset.",
    "ncbi_link": "HAD4: 810737"
  },
  {
    "caption": "B. Relative  parasitemia was assessed for the untransfected DiCre 3D7 parental line and transfectant parasite lines with AMR1 under inducible disruption. Rapamycin/glucosamine treatment began on cycle zero and parasitemia determined by  flow cytometry  and compared to identical lines that were left untreated. Data represents the mean relative parasitemia ± SEM from three biological replicates (y-axis) across seven replication cycles (x-axis).",
    "ncbi_link": "DiCre: 2777477
AMR1: 813884"
  },
  {
    "caption": "D.  Pyrimidine biosynthetic intermediates accumulate when SHMT-M is disrupted compared to the DiCre parental line (C) following rapamycin/glucosamine treatment (mean ±SEM). Pyrimidine biosynthetic disruption islinked to  dihydroorotate dehydrogenase (DHODH) inhibition and blockage of the mitochondrial electron transport chain (mETC). Ubiquinone (Q) is the necessary electron carrier for the  mETC.",
    "ncbi_link": "DiCre: 2777477
SHMT-M: 812116"
  },
  {
    "caption": "E. Asexual growth when SHMT-M is depleted. Parasitemia was determined across seven replication cycles (x-axis) via flow cytometry and presented as the mean ± SEM from three independent experiments. Decylubiquinone (Dub) was added at 10 µM to determine if the growth defect observed was due to impaired ubiquinone synthesis or recycling.",
    "ncbi_link": "SHMT-M: 812116"
  },
  {
    "caption": "Representative low (left) and high (right) power images of H&E-stained lung sections from KrasG12D, KrasG12D:Adam17ex/+ and KrasG12D:Adam17ex/ex mice at 6 weeks post Ad-Cre inhalation. Scale bars, 3mm (left) and 300μm (right). Quantification of lung parenchyma area occupied by tumor lesions (B), and tumor incidence (C), per whole mouse lung in the indicated genotypes (n = 6 per genotype).",
    "ncbi_link": "Cre: 
Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "Representative images of PCNA-stained lung sections from KrasWT, KrasG12D and KrasG12D:Adam17ex/ex mice at 6 weeks post Ad-Cre (for KrasG12D) or vehicle (for KrasWT) inhalation. Scale bar, 100μm. Quantification of PCNA-positive cells/high power field (HPF) in the indicated mouse lungs (n = 6 per genotype).",
    "ncbi_link": "Cre: 
Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "qPCR expression analyses of cell cycle regulation genes (normalized against 18SrRNA) in lungs from the indicated mice (n = 6 per genotype). *",
    "ncbi_link": "18SrRNA: 19791"
  },
  {
    "caption": "Representative immunoblots of KrasG12D and KrasG12D:Adam17ex/ex lung lysates with the indicated antibodies. Each lane is an individual mouse sample. Semi-quantitative densitometry of Myc protein levels (relative to Actin) in lung lysates from (D). n = 6 per genotype.",
    "ncbi_link": "Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "Representative immunofluorescence images of lung sections of KrasG12D mice (6 weeks post Ad-Cre inhalation) co-stained for ADAM17 and markers for club cells (CC10) (A), alveolar type II (surfactant protein-C, SP-C) (B) and type I (Podoplanin, Pdpn) (C) cells, total immune cells (CD45) (D) and endothelial cells (CD31) (E). DAPI nuclear staining is blue. Scale bars, 100μm. Arrowheads in merged images indicate dual-positive ADAM17-expressing cells. Quantification of immunofluorescence staining from A-E (n = 5 mice per stain).",
    "ncbi_link": "Cre: 
Kras: 16653"
  },
  {
    "caption": "Representative images of H&E-stained lung sections from KrasG12D recipient mice reconstituted with KrasG12D (KrasKras) or KrasG12D:Adam17ex/ex bone marrow (KrasKras:ex/ex). Scale bar, 3mm. Quantification of lung parenchyma area occupied by tumor lesions in the indicated bone marrow chimeras (n = 6 mice per group).",
    "ncbi_link": "Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "Representative images of pADAM17-stained lung sections from KrasWT and KrasG12D (6 weeks post inhalation) mice. Scale bar, 100μm. Quantification of pADAM17-positive cells/high power field (HPF) in lungs of KrasWT and KrasG12D mice (n = 6 per genotype).",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Representative immunoblots of individual KrasWT and KrasG12D mouse lung lysates with the indicated antibodies. Semi-quantitative densitometry of pADAM17 in lung lysates (n = 6 per genotype).",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Representative immunoblots of individual KrasWT and KrasG12D lung lysates with the indicated antibodies. Semi-quantitative densitometry of pp38 and pERK1/2 MAPK protein levels in KrasWT and KrasG12D lung lysates (n = 6 per genotype).",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Representative images of pADAM17-stained lung sections from KrasG12D mice injected with a single dose of vehicle (control), SB203580 p38 MAPK or U0126 ERK1/2 inhibitors. Scale bar, 100μm.",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Representative immunoblots of individual KrasG12D and KrasG12D:Adam17ex/ex lung lysates with the indicated antibodies.",
    "ncbi_link": "Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "ELISA of sIL-6R and TNFα protein levels in serum from KrasG12D and KrasG12D:Adam17ex/ex mice at 6 weeks post Ad-Cre inhalation, along with control KrasWT mice at 6 weeks post vehicle inhalation (n = 6 per genotype).",
    "ncbi_link": "Cre: 
Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "Immunoblots of representative individual KrasWT, KrasG12D and KrasG12D:Adam17ex/ex lung lysates with the indicated antibodies.",
    "ncbi_link": "Adam17: 11491
Kras: 16653"
  },
  {
    "caption": "Representative immunofluorescence staining of KrasG12D mouse lung sections (n = 5 mice) for ADAM17 and either (panels from left to right) IL-6R, TGFα, Notch1, Nrg1 and EGF. Sections were counterstained with DAPI (blue). Scale bars, 100μm.",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Representative images of pERK1/2-stained lung sections from KrasG12D mice treated with either vehicle (control, Ctl) or anti-IL-6R antibodies 1F7 or 25F10 over 6 weeks post Ad-Cre inhalation. Scale bar, 100μm. Quantification of pERK1/2-positive cells/high power field (HPF) in lungs of the indicated groups (n = 5 per group).",
    "ncbi_link": "Cre: 
Kras: 16653"
  },
  {
    "caption": "Representative immunoblots with the indicated antibodies on whole cell lysates from primary immune and epithelial cells isolated from the lungs of mice (n = 3) harbouring the oncogenic KrasG12D allele that were stimulated with either PBS (-) or 100ng/ml Hyper-IL-6 (+). Graphs depict semi-quantitative densitometry of pERK1/2 MAPK protein levels in stimulated immune and epithelial cells (n = 2 experiments).",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "Quantification of pADAM17-positive cells and pERK1/2 MAPK-positive cells in LAC patients either KRAS wild-type (WT, n = 13) or mutant (MUT, n = 5).",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "Linear regression analyses of pADAM17 with pERK1/2 (D) and pp38 (E) MAPK staining in serial lung sections from LAC KRAS wild-type and mutant patients.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "MTT viability assays of A549 cells transduced with nontargeted control sgRNA (Ctl) and ADAM17 sgRNA (knockout, KO).",
    "ncbi_link": "ADAM17: 6868"
  },
  {
    "caption": "ATP proliferation (J) assays of A549 cells transduced with nontargeted control sgRNA (Ctl) and ADAM17 sgRNA (knockout, KO).",
    "ncbi_link": "ADAM17: 6868"
  },
  {
    "caption": "Representative images of H&E-stained lung sections from KrasG12D mice treated with either vehicle (control) or the ADAM17 prodomain inhibitor, A17pro (1mg/kg, 3 times a week), for 6 weeks starting on the day after Cre inhalation. Scale bars, 3mm. Quantification of lung parenchyma area occupied by tumor lesions in the indicated groups (n = 6 per group)",
    "ncbi_link": "Cre: 
Kras: 16653"
  },
  {
    "caption": "Tumor volume (mm3) of a KRAS mutant PDX treated with vehicle control (Ctl) or A17pro (1mg/kg) every second day. Treatment started when tumors reached a volume of 100-150mm3 after injection of 2 × 106 cells in NSG mice. n = 5 per group.",
    "ncbi_link": "KRAS: 16653"
  },
  {
    "caption": "Representative image of pADAM17 immunohistochemical staining on an untreated KRAS mutant PDX tumor. Scale bar, 100μm.",
    "ncbi_link": "KRAS: 16653"
  },
  {
    "caption": "A-L First column shows the triple immunolabelling of CETN3 (green), PCNT (red) and SYCP3 (grey) on squashed WT mouse spermatocytes. Second column shows the correspondent labellings for Plk1(∆/∆). Third column shows signals for BI2536-treated spermatocytes. Images are shown for (A, E, I) zygotene, (B, F, J) pachytene, (C, G, K) diplotene and (D, H, L) diakinesis. Amplifications at 300% magnification for all labellings are displayed for each image. M-O Quantification of the percentage of cells without PCNT at centrosomes (PCNT-) in (M) zygotene, (N) pachytene and (O) diplotene in control, Plk1(∆/∆) and BI2536-treated spermatocytes. Data for BI2536 represent results for 100µM at 8h treatment on organotypic cultures of seminiferous tubules. Data are presented as mean ± SD for three biological replicates for each condition. ",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "A-C Immunolabelling of γ-Tubulin and SYCP3 during prophase I in control, Plk1(∆/∆) and BI2536-treated spermatocytes. Images are show for pachytene, diplotene and diakinesis in Control (A), Plk1(∆/∆) (B) and BI2536-treated spermatocytes (C). First columns show the double immunolabelling of PCM -PCNT- (green) and SYCP3 (red), and second columns shows γ-Tubulin (γ-Tub, magenta) and SYCP3 (red). Chromatin has been stained with DAPI (blue). Amplifications at 300% magnification for all labellings are displayed for each image. Data for BI2536 represent results for 8h at 100µM treatment on organotypic cultures of seminiferous tubules",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "(D) Immunolabelling of CETN3 and γ-Tubulin in control and Plk1(∆/∆). Double immunolabelling of CETN3 (red) and γ-Tubulin (green) in pachytene (a-b) and diakinesis (c-d). Chromatin has been stained with DAPI (blue).",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "(E) Quantification of the number of cells without γ-Tubulin at centrosomes (γ-Tub -) in pachytene and diplotene spermatocytes in control, Plk1(∆/∆) and BI2536-treated spermatocytes. Data represent average of two biological replicates per condition.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "A-D Control: Double immunolabelling of SYCP3 (cyan) and α-Tubulin (red) on control squashed spermatocytes for the first and the second meiotic divisions at metaphase I (A) and metaphase II (B). Double immunolabelling of PCNT (green) and α-Tubulin (red) on control squashed spermatocytes at metaphase I (C) and metaphase II (D). Chromatin has been stained with DAPI (pseudo coloured in grey). E-H Plk1 (∆/∆) mouse model: Double immunolabelling of SYCP3 (cyan) and α-Tubulin (red) in monopolar spindle I (E) and monopolar spindle II (F). Double immunolabelling of PCNT (green) and α-Tubulin (red) labelling in monopolar spindle I (G) and monopolar spindle II (H). Chromatin has been stained with DAPI (pseudo coloured in grey). I-L BI2536-treated spermatocytes: Double immunolabelling of SYCP3 (cyan) and α-Tubulin (red) at monopolar spindle I (I) and monopolar spindle II (J). Double immunolabelling of PCNT (green) and α-Tubulin (red) labelling in monopolar spindle I (K) and monopolar spindle II (L). Chromatin has been stained with DAPI (pseudo coloured in grey). Cells shown were treated for 100µM BI2536 for 8h treatment on organotypic cultures of seminiferous tubules. M-P MLN8237-treated spermatocytes: Double immunolabelling of PCNT (green) and α-Tubulin (red) in monopolar spindle I (M) and monopolar spindle II (N). Double immunolabelling of PCNT (green) and α-Tubulin (red) in monopolar spindle I (O) and monopolar spindle II (P). Chromatin has been stained with DAPI (pseudo coloured in grey). Cells shown were treated for 10µM MLN8237 for 8h treatment on organotypic cultures of seminiferous tubules. ",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "A-B AURKP distribution in control, Plk1(Δ/Δ), 100µM 8h BI2536-treated and 10µM 8h MLN8237-treated spermatocytes. (A) Double immunolabelling of AURKP (grey/green) and α-Tubulin (red) in control, Plk1(Δ/Δ), BI2536-treated and MLN8237-treated spermatocytes. Images are shown for bipolar spindles I and II for each condition. (B) Monopolar spindles I and II are shown for Plk1(Δ/Δ), BI2536-treated and MLN8237-treated spermatocytes. Chromatin has been stained with DAPI (blue)..",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "(E) Quantitative analysis of AURKP signal at cell poles. Experiments were conducted for two biological replicates. Number of cells analysed: control (n=32), Plk1(Δ/Δ) (n=27), BI2536-treated spermatocytes (n= 27). Data are mean ± SD; (****) p<0.0001, Student's t-test.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "(A) Triple immunolabelling of CEP250 (green), CETN3 (magenta) and SYCP3 (grey) in (a-b) late diplotene and (c-d) metaphase I in control and Plk1(Δ/Δ) spermatocytes.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "(B) Double immunolabelling of KIF11 (grey/green), and SYCP3 (red) in (a) control spindle, (b) Plk1(Δ/Δ) monopolar spindle, (c) BI2536 monopolar spindle and (d) MLN8237 monopolar spindle. Chromatin has been stained with DAPI (bue). Data is presented for 100µM BI2536 and 10µM MLN8237 for 8h treatments on organotypic cultures of seminiferous tubules.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "A HEK293T were transfected with NF-kBluciferase reporter plasmid and FLAG-tagged full-length CARD14 (FL) or CARD14sh (short) at the indicated concentrations and analyzed 24 h later. (A) NF-kB reporter gene expression.",
    "ncbi_link": "luciferase: 
NF-kB: 
CARD14: 79092"
  },
  {
    "caption": "HEK293T were transfected with NF-kB luciferase reporter plasmid and FLAG-tagged full-length CARD14 (FL) or CARD14sh (short) at the indicated concentrations and analyzed 24 h later. (B) IL-8 secretion. Values are the mean of triplicates ± s.e. P-values are compared against empty vector treatment. Significance levels, ns P>0.05, *P<0.05, **P<0.01 and ***P<0.001 by student t test. Unless otherwise stated, p-values are p<0.001.",
    "ncbi_link": "luciferase: 
NF-kB: 
CARD14: 79092"
  },
  {
    "caption": "HEK293T were transfected with NF-kB luciferase reporter plasmid and FLAG-tagged full-length CARD14 (FL) or CARD14sh (short) at the indicated concentrations and analyzed 24 h later. (C) Immunoblotting for c-Jun, phospho-c-Jun, JNK, phospho-JNK, p38 and phospho-p38 as indicated. Actin was used as a loading control. Data are representative of two independent experiments.",
    "ncbi_link": "luciferase: 
NF-kB: 
CARD14: 79092"
  },
  {
    "caption": "(A) MALT1 interacts with CARD14sh in a BCL10-dependent manner. HEK293T cells were transfected with FLAG-CARD14sh, Myc-MALT1 and FLAG-BCL10 as indicated. 24 h later, MALT1 was immunoprecipitated (IP) from cell lysates with anti-MALT1. CARD14sh and BCL10 co-immunoprecipitation with MALT1 was detected by immunoblotting with anti-FLAG. Immunoprecipitated MALT1 was detected by immunoblotting with anti-myc. The closed arrowhead shows the position of CARD14, the double arrowhead shows the position of BCL10. The asterisk indicates a non-specific band. Total expression levels of transfected proteins are shown by immunoblotting of a fraction of the cell lysates with the indicated antibodies (bottom panel).",
    "ncbi_link": "BCL10: 8915
CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(B) MALT1 co-expression potentiates CARD14sh-induced JNK and p38 MAP kinase activation. HEK293T cells were transfected with the indicated concentrations of FLAG-tagged CARD14sh, with or without MALT1 (30ng). Transfection with FLAG-TRAF6 and FLAG-CARD11(L232LI) were used as a positive control. c-Jun accumulation, JNK and p38 phosphorylation were analyzed by immunoblotting with the antibodies indicated. Actin was used as a loading control.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "(C) MALT1 co-expression potentiates NF-kB activation by pathogenic CARD14 mutants. HEK293T were transfected with NF-kB reporter plasmid and wild-type (WT) FLAG-CARD14 or the indicated psoriasis-associated CARD14 mutants (15ng), with or without MALT1 (15ng). Luciferase activity in cell lysates was measured after 24 h. Values are the mean of triplicates ± s.e. Significance levels, *P<0.05, **P<0.01 and ***P<0.001 by student t test. Expression of transfected proteins was verified by western blotting (bottom panel).",
    "ncbi_link": "NF-kB: 
CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(D) CARD14(E138A) mutation enhances MALT1 binding. HEK293T cells were transfected with wild-type (WT) FLAG-CARD14sh or the indicated CARD14sh mutants and Myc-MALT1. 24 h later, MALT1 was immunoprecipitated (IP) from cell lysates with anti-MALT1 and CARD14 co-immunoprecipitation was detected by immunoblotting with anti-FLAG. Immunoprecipitated MALT1 was detected by immunoblotting with anti-MALT1. The asterisk indicates a non-specific band. Immunoprecipitation with a non-relevant antibody (rIgG) was used as a negative control (first lane). Total expression levels of transfected proteins are shown by immunoblotting of total cell lysates (bottom panel). Data are representative of two independent experiments.",
    "ncbi_link": "CARD14: 79092"
  },
  {
    "caption": "(A) MALT1 expression is essential for CARD14sh-induced NF-kB activation. MALT1-deficient HEK293T cells were transfected with NF-kB reporter plasmid and the indicated expression plasmids. Luciferase activity in cell lysates was measured 24 h later. CARD11(L232LI) and TRAF6 transfection were used as MALT1-dependent and MALT1-independent controls, respectively. Values are the mean of triplicates ± s.e. Expression of the transfected plasmids was verified by immunoblotting (lower panel).",
    "ncbi_link": "NF-kB: 
CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(B) MALT1 expression is essential for CARD14sh-induced JNK activation. MALT1-deficient HEK293T cells were transfected with FLAG-CARD14sh (30ng) either alone or together with either wild-type (MALT1WT) or catalytically inactive MALT1 (MALT1C/A) as indicated. c-Jun accumulation and JNK phosphorylation were analyzed by immunoblotting with the antibodies indicated. Actin was used as a loading control.",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(C) MALT1 deficiency inhibits CARD14-induced gene expression in HaCaT keratinocytes. HaCaT cells were transfected with scrambled (scr) or MALT1-targeting siRNA prior to doxycycline-induced CARD14 expression as described in materials and methods. IL-8 and MCP-1 concentration in the cell supernatants was measured 8 h (IL-8) or 24 h (MCP-1) later by ELISA. Values are the mean of triplicates ± s.e. Doxycycline-induced CARD14 expression and MALT1 knock-down were verified by immunoblotting (right panel). Data are representative of two independent experiments.",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(A) CARD14 signaling induces CYLD and A20 cleavage. HEK293T cells were transfected with different concentrations of FLAG-CARD14, with or without MALT1 as indicated. CARD11(L232LI) transfection was used as a positive control. Endogenous CYLD and A20 processing was analyzed by immunoblotting. CYLD and A20 cleavage fragments are indicated by an arrow.",
    "ncbi_link": "CARD11: 84433
CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(B) CARD14 signaling induces CYLD cleavage after R324. HEK293T cells were transfected with different concentrations of FLAG-CARD14sh and either wild-type (CYLDWT) or non-cleavable CYLD (CYLDR324A). CYLD processing was analyzed by immunoblotting. The CYLD cleavage fragment is indicated by an arrow.",
    "ncbi_link": "CARD14: 79092
CYLD: 1540"
  },
  {
    "caption": "(C) Expression of catalytically active MALT1 is necessary for CARD14-induced CYLD cleavage. MALT1-deficient HEK293T cells in which MALT1 expression was restored by transfection with different concentrations of either wild-type (MALT1WT) or catalytically inactive MALT1 (MALT1C/A), were co-transfected with FLAG-CARD14sh and CYLD as indicated. CYLD processing was analyzed by immunoblotting. The CYLD cleavage fragment is indicated by an arrow.",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(D) Psoriasis-associated CARD14 mutation enhances activation of MALT1 proteolytic activity. HEK293T cells were transfected with wild-type (WT) FLAG-CARD14 or different psoriasis-associated CARD14 mutants (20ng), with or without MALT1 (20 ng) as indicated. Endogenous CYLD and A20 processing, as well as IκBα phosphorylation, were analyzed by immunoblotting. The CYLD and A20 cleavage fragments are indicated by an arrow.",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(E) Pharmacological inhibition of MALT1 proteolytic activity prevents CARD14-induced gene expression in HaCaT keratinocytes. CARD14 expression was induced by doxycycline (dox) treatment in the absence or presence of different concentrations of mepazine as indicated. The next morning, cell culture medium was refreshed and IL-8 and MCP-1 concentration in the cell supernatant was measured 8 h later by ELISA. TNF stimulation (MALT1-independent) was used as a negative control. Values are the mean of triplicates ± s.e. Data are representative of two independent experiments. Significance levels, *P<0.05, **P<0.001, ***P<0.001 by student t test.",
    "ncbi_link": "CARD14: 79092"
  },
  {
    "caption": "(A-B) CYLD and A20 inhibit CARD14sh-induced NF-kB activation. HEK293T cells were transfected with NF-kB reporter plasmid and FLAG-tagged CARD14sh (30ng), with or without the indicated concentrations of CYLD (A) or A20 (B). Luciferase activity in cell lysates was measured 24 h later. Closed arrowheads indicate full length A20 and CYLD; arrows indicate cleaved A20 and CYLD. Data are representative of three independent experiments.",
    "ncbi_link": "Luciferase: 
NF-kB: 
CARD14: 79092"
  },
  {
    "caption": "(C) A20 and ABIN-1 inhibit CARD14-induced NF-kB activation. HEK293T cells were transfected with NF-kB reporter plasmid, A20 (3 ng) or ABIN1 (15ng) and the indicated concentrations of FLAG-tagged CARD14sh. Luciferase activity in cell lysates was measured 24 h later. Values are the mean of triplicates ± s.e. Protein expression of transfected plasmids was verified by western blot and is shown in the accompanying panels.",
    "ncbi_link": "Luciferase: 
NF-kB: 
CARD14: 79092
A20: 7128
ABIN-1: 10318"
  },
  {
    "caption": "(D) A20 inhibits CARD14-induced NF-kB activation through its ZnF domains. HEK293T cells were transfected with NF-kB reporter plasmid, FLAG-CARD14sh (20ng) and wild-type (WT) or mutant A20 expression plasmids (3ng) as indicated. Luciferase activity in cell lysates was measured after 24 h. CARD14 and A20 expression was measured by immunoblotting (bottom panel). Data are representative of two independent experiments.",
    "ncbi_link": "Luciferase: 
NF-kB: 
CARD14: 79092
A20: 7128"
  },
  {
    "caption": "(A) CARD14(E138A) induces cytokine and chemokine expression in human primary keratinocytes. Cells were transfected with empty vector (EV) or CARD14(E138A) as indicated. 24 h later, the secretion of 36 different human cytokines, chemokines, and acute phase proteins was analyzed via a multiplex antibody array. Quantification was done using ImageJ software and is expressed as relative CARD14/EV values for a selected number of proteins (bottom panel).",
    "ncbi_link": "CARD14: 79092"
  },
  {
    "caption": "(B) MALT1 deficiency inhibits CARD14(E138A)-induced cytokine and chemokine expression in human primary keratinocytes. Cells were transfected with scrambled (scr) or MALT1-targeting siRNA as indicated, 48 h later followed by transfection with CARD14(E138A). After 24 h, cytokine and chemokine expression was analyzed and is expressed as described in (A).",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(C) Pathogenic CARD14 mutation enhances MALT1-dependent CARD14-induced IL-8 expression in human primary keratinocytes. Cells were transfected with scrambled (scr) or MALT1-targeting siRNA as indicated, 48 h later followed by transfection with CARD14 wild-type (WT), CARD14(G117S) or CARD14(E138A) as indicated. TNF treatment was used as a control. After 24 h, IL-8 concentration in the cell supernatant was analyzed via ELISA. Values are the mean of triplicates ± s.e. Expression levels of MALT1 and CARD14 variants is verified by immunoblotting (bottom panel).",
    "ncbi_link": "CARD14: 79092
MALT1: 10892"
  },
  {
    "caption": "(D) Pharmacological inhibition of MALT1 proteolytic activity inhibits CARD14-induced IL-8 production and A20 processing in human primary keratinocytes. Cells were transfected with different CARD14 variants in the presence or absence of mepazine as indicated. TNF treatment was used as a control. 24 h later, IL-8 levels in the cell supernatant were measured by ELISA. Values are the mean of triplicates ± s.e. Expression of different CARD14 variants and CARD14-induced processing of endogenous A20 were analyzed by immunoblotting. Data are representative of two independent experiments. Significance levels, *P<0.05, **P<0.001, ***P<0.001 by student t test.",
    "ncbi_link": "CARD14: 79092"
  },
  {
    "caption": "(A) miR-155 expression levels were examined in the lungs of normal uninfected or H37Rv infected BALB/c mice 6 weeks postinfection",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(B) Murine bone marrow-derived macrophages (BMDMs) were infected with BCG at an MOI of 5 for the indicated times, and the expression levels of miR-155 were measured by real-time PCR.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(C and D) RAW264.7 cells were infected with BCG at an MOI of 5 for the indicated time points (C) or at indicated MOIs for 24 h (D). The expression levels of miR-155 were examined by real-time PCR.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(E and F) RAW264.7 cells were infected with H37Ra at an MOI of 5 for the indicated time (E) or at indicated MOI for 24 h (F). The expression levels of miR-155 were examined by real-time PCR. Data are shown as the mean ± SEM of three independent experiments. *, p<0.05; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A-C) RAW264.7 cells were transfected with control or miR-155 mimic for 24 h followed by BCG (A), H37Ra (B) or H37Rv (C) infection at an MOI of 10 for 1 h, and intracellular mycobacterial viability was determined by CFU assay at the indicated timepoints.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(D-F) RAW264.7 cells were transfected with control or miR-155 inhibitor for 24 h followed by BCG (D), H37Ra (E) or H37Rv (F) infection at an MOI of 10 for 1 h, and intracellular mycobacterial viability was determined by CFU assay at the indicated timepoints.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(G and H) RAW264.7 cells were transfected with miR-155 mimic (G) or inhibitor (H) for 24 h followed by Texas Red-labeled BCG infection at an MOI of 10 for 1 h. Phagocytosis of mycobacteria was determined by flow cytometry. Data are shown as the mean ± SEM of three independent experiments. *, p<0.05; **, p<0.01.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "RAW 264.7 cells were transiently transfected with control or miR-155 mimic for 24 h and then infected with Texas Red-labeled BCG for 1 h. Lysosomes were immunolabeled with CD63 antibody followed by Alexa Fluor 488-conjugated goat anti-rabbit IgG antibody (A)The colocalization of BCG with lysosome was detected by confocal microscopy. The percentage of co-localization of BCG with CD63-positive (B)",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "RAW 264.7 cells were transiently transfected with control or miR-155 mimic for 24 h and then infected with Texas Red-labeled BCG for 1 h. Lysosomes were immunolabeled with CD63 antibody followed by Alexa Fluor 488-conjugated goat anti-rabbit IgG antibody (A), or labeled with a fluorogenic substrate for proteases, DQ-Green (C). The colocalization of BCG with lysosome was detected by confocal microscopy. The percentage of co-localization of BCG with CD63-positive (B) or DQ-Green labeled (D) lysosomes was quantified, respectively. Cells treated with rapamycin were used as a positive control. Arrows indicate the co-localization of BCG with lysosomes; scale bar = 5 µm. Quantification of data are shown as the mean ± SEM of three independent experiments (n = 100 phagosomes). **, p<0.01.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A-D) RAW264.7 cells were transfected with miR-155 mimic (A and C) or inhibitor (B and D) for 24 h and then either left uninfected or infected with BCG. Expression levels of miR-155 were detected by real-time PCR (A and B).",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A-D) RAW264.7 cells were transfected with miR-155 mimic (A and C) or inhibitor (B and D) for 24 h and then either left uninfected or infected with BCG. Expression levels of miR-155 were detected by real-time PCR (A and B). The LC3 levels were detected by Western-blot, and the ratios of LC3-II/β-actin were calculated as shown below the representative blot (C and D)",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(E and F) RAW264.7 cells transfected with miR-155 mimic (E) or inhibitor (F) was incubated with DMSO or bafilomycin A1 (BafA.) at a concentration of 100 nM for 2 h, and then LC3 levels were detected by Western-blot. The ratios of LC3-II/β-actin were calculated as shown below the representative blot. ***, p<0.001.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A and B) RAW264.7 cells stably expressing GFP-LC3 were transiently transfected with control or miR-155 mimic for 24 h, and GFP-LC3 puncta (>1 µm) were detected by confocal microscopy (A) and quantified (B).",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "RAW264.7 cells were transiently transfected with control or miR-155 mimic for 24 h. Endogenous LC3 was stained with LC3 antibody followed by Alexa Fluor 488-conjugated goat anti-rabbit IgG (Green), and LC3 puncta (>1 µm) were detected by confocal microscopy (C) and quantified (D).",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(E and F) RAW264.7 cells were transiently transfected with control or miR-155 mimic for 24 h, and then incubated with a specific fluorescent dye MDC (50 µM). The MDC-labeled autophagic vacuoles were detected by confocal microscopy (E) and cells with MDC-positive autophagic vacuoles were quantified (F). Cells treated with rapamycin were used as a positive control. Arrows indicate the GFP-LC3 puncta or autophagic vacuoles labeled with MDC; scale bar = 5 µm. Data are shown as the mean ± SEM of three independent experiments (n = 300 cells). **, p<0.01; ***, p<0.001.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A) RAW264.7 cells stably expressing GFP-LC3 were transiently transfected with control or miR-155 mimic and then infected with Texas Red-labeled BCG for 1 h. The co-localization of BCG with LC3 was detected by confocal microscopy. (B) Quantification of the co-localization of BCG with LC3-positive autophagosomes is shown.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(C) RAW264.7 cells were transiently transfected with control or miR-155 mimic, and then infected with Texas Red-labeled BCG for 1 h. Endogenous LC3 was stained with LC3 antibody followed by Alexa Fluor 488-conjugated goat anti-rabbit IgG (Green). The co-localization of BCG with endogenous LC3 was detected by confocal microscopy. (D) Quantification of the co-localization of BCG with LC3-positive autophagosomes is shown.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(E) After transient transfection with control or miR-155 mimic, RAW264.7 cells were infected with Texas Red-labeled BCG for 1 h, and then were labeled with a specific fluorescent dye MDC (50 µM) for autophagic vacuoles. The co-localization of BCG with MDC-positive autophagic vacuoles was detected by confocal microscopy. (F) Quantification of the co-localization of BCG with MDC-positive autophagosomes is shown. Cells treated with rapamycin were used as a positive control. Arrows indicate the co-localization of BCG with autophagosomes; scale bar = 5 µm. Data are shown as the mean ± SEM of three independent experiments (n = 100 phagosomes). **, p<0.01; ***, p<0.001.",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(A and B) RAW 264.7 cells were transiently transfected with control or miR-155 mimic for 24 h, and then incubated with DMSO or 3-MA for 2 h. Protein levels of LC3 were detected by Western-blot in uninfected cells (A)",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(C and D) RAW 264.7 cells were transiently co-transfected with control or miR-155 mimic together with a control siRNA or Atg7 siRNA. The expression levels of Atg7 and LC3 were detected by Western-blot (C).",
    "ncbi_link": "Atg7: 74244
miR-155: RF00731"
  },
  {
    "caption": "(A) Sequences of mouse and human miR-155 and their predicted interactions with conserved 7-mer 1A miR-155 seeds found within the Rheb 3′UTRs of different species are shown. The sequence of the Rheb 3′UTR seed mutant used for the reporter assays and the predicted disruption of the miR-155 interaction are also shown.",
    "ncbi_link": "miR-155: RF00731
Rheb: 19744"
  },
  {
    "caption": "B) RAW264.7 cells were co-transfected with control or miR-155 mimic and a wild-type (WT-Rheb) or mutated Rheb 3′UTR (mut-Rheb) luciferase reporter plasmid and assessed for luciferase activity at 24 h after transfection. Data are shown as the mean ± SEM of three independent experiments. ***, p<0.001; NS, not significant.",
    "ncbi_link": "miR-155: RF00731
Rheb: 19744"
  },
  {
    "caption": "(C-F) RAW264.7 cells were transfected with miR-155 mimic (C and E) or inhibitor (D and F) for 24 h and either left uninfected or infected with BCG. Protein expression levels of Rheb were detected by Western-blot. Values of Rheb/β-actin ratios are indicated below the representative blot (C and D)",
    "ncbi_link": "miR-155: RF00731"
  },
  {
    "caption": "(C-F) RAW264.7 cells were transfected with miR-155 mimic (C and E) or inhibitor (D and F) for 24 h and either left uninfected or infected with BCG. Protein expression levels of Rheb were detected by Western-blot. Values of Rheb/β-actin ratios are indicated below the representative blot (C and D), and expression levels of Rheb mRNA were detected by RT-PCR (E and F).",
    "ncbi_link": "β-actin: 
miR-155: RF00731
Rheb: 19744"
  },
  {
    "caption": "(A) RAW264.7 cells were transfected with a plasmid expressing Rheb for 24 h, and then incubated with DMSO or BafA. for 2 h. The expression levels of Rheb and LC3 were detected by Western-blot. Values of LC3-II/β-actin ratios are indicated below the representative blot.",
    "ncbi_link": "Rheb: 19744"
  },
  {
    "caption": "(B and C) RAW264.7 cells were co-transfected with control or miR-155 mimic together with a control plasmid or a plasmid expressing Rheb for 24 h, and then infected with Texas Red-labeled BCG for 1 h. The co-localization of BCG and MDC-labeled autophagosome was detected by confocal microscopy. Arrows indicate Quantification of BCG co-localization with autophagosomes described in B is shown (C).",
    "ncbi_link": "miR-155: RF00731
Rheb: 19744"
  },
  {
    "caption": "D) RAW264.7 cells were co-transfected with control or miR-155 mimic together with a control plasmid or a plasmid expressing Rheb for 24 h. Cells were infected with BCG for 1 h, and washed for three times to remove extracellular mycobacteria. Intracellular mycobacterial viability was determined by CFU assay at the indicated timepoints. Data are shown as the mean ± SEM of three independent experiments. *, p<0.05; **, p<0.01; NS, not significant.",
    "ncbi_link": "miR-155: RF00731
Rheb: 19744"
  },
  {
    "caption": "A549* cells expressing or lacking TMPRSS2 were pretreated with MG-132 at the indicated concentrations and subsequently infected with SARS-CoV-2 (MOI ~0.2) in the continuous presence of the drug. The proportion of infected cells was quantified by flow cytometry as described in Fig. 1D, and data were normalized to that from control samples for which MG-132 had been omitted. n = 6 biological replicates.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "A549* expressing or lacking TMPRSS2 cells and Vero cells were first infected with SARS-CoV-2 at MOIs of 0.1 and 0.2, respectively, for 24 h and then cocultured for 5 h along with target cells, not infected but prestained with CMFDA, a cytosolic green dye. Cells were subsequently treated with trypsin or furin for 5 min at 37°C and left to coculture for an additional hour at 37°C. After fixation, nuclei were stained with Hoechst (blue), and infected cells were subjected to immunofluorescence staining against SARS-CoV-2 nucleoprotein (magenta). Samples were ultimately imaged by confocal fluorescence microscopy. White stars indicate syncytia with at least four nuclei. Scale bars: 100 µm. Images of microscope fields obtained in (E) were quantified [A549*: n (no virus) = 30, n (no protease) = 80, n (trypsin) = 80, and n (furin) = 60; A549* TMPRSS2: n (no virus) = 30, n (no protease) = 80, n (trypsin) = 79, and n (furin) = 60; Vero: n (no virus) = 40, n (no protease) = 112, n (trypsin) = 114, and n (furin) = 60]. The fusion index is given as f = 1 - [(number of cells in a field after fusion)/(number of nuclei)].",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "Inverted invasion assays were performed with PDAC tumor cell lines from KPC and KPflC mice. Tumor cell lines bearing mutant p53R172H (KPC) invade significantly further than tumor cells with deletion of 1 copy of p53 (KPflC) (P ≤ 0.01). Data are shown as the average of four wells + SEM.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "Introduction of shRNA targeting Lox into KPC tumor cells significantly inhibits invasion (P ≤ 0.01 by unpaired Student's t-test). Data are shown as the average of four wells + SEM.",
    "ncbi_link": "Lox: 16948"
  },
  {
    "caption": "Introduction of exogenous LOX into KPflC tumor cells significantly promotes invasion (left panel, P ≤ 0.01 by unpaired Student's t-test). LOX expression was assessed by immunoblotting (right panel). Columns indicate the mean of four well and error bars indicate SEM.",
    "ncbi_link": "LOX: 16948"
  },
  {
    "caption": "Representative confocal  images of coronal  slices of the core of the olfactory bulb (OB) obtained from RiboTag mice  injected with AVV-hGFAP-mycCRE particles. In (E) mice  were analysed 16 weeks after injection in the lateral ventricle or in the lateral corner as indicated. Scale bars = 20 µm. (F) Quantification of RiboTag-HA  (HA)+ and/or DCX+ cells in the OB  in N ≥ 2. Data information: N number refers to biological replicates; for each biological replicate at least three technical replicates were performed. Bars represent mean ± SEM.* indicates significance: *p<0.05, determined by two-way ANOVA with Sidak's multiple comparisons test.",
    "ncbi_link": "myc: 
CRE: 2777477
GFAP: 2670"
  },
  {
    "caption": "(A, B) Representative micrographs  of the  V-SVZ of mice  injected with an AAV  overexpressing GFP  and a shRNA against Hes1  (AAV Hes1-sh) or a scrambled sequence (AAV  sc-sh). Coronal  sections were stained  with either notch intracellular domain (NICD, A) or Ki67  to visualize cycling cells (B). DAPI  was used for nuclear counterstain, scale bars indicate 20 µm. Arrows indicate apical GFP+ (white) and basal GFP- (yellow) cells displaying NICD staining. Quantification of fold change in NICD-levels; N = 3 (C), Ki67+ cells; N = 5 (D) Data information: N number refers to biological replicates; for each biological replicate at least three technical replicates were performed. Bars represent mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, determined by two-way ANOVA with Sidak's multiple comparisons test",
    "ncbi_link": "GFP: 
Hes1: 15205"
  },
  {
    "caption": "Reverse Transcriptase PCR showing that bd1971, and control gene dnaK, are expressed throughout the predatory cycle of Bdellovibrio bacteriovorus. RNA was isolated at the time points indicated across the top of the gel during one round of synchronous Bdellovibrio infection of E. coli cells. Primers were designed to anneal specifically to the gene of interest. L = 100bp DNA ladder, AP = Attack Phase cells, 15-45 = 15-45 minutes respectively since infection, 1h-4h = hours respectively since infection. Ec = E. coli strain S17-1 RNA (negative control: no Bdellovibrio RNA); NT = control with no template RNA; gen = B. bacteriovorus HD100 genomic DNA (positive control). The cartoon above represents each stage in the predatory cycle.",
    "ncbi_link": "bd1971: 
dnaK: "
  },
  {
    "caption": "Relative levels of c-di-GMP in matched cell biomass host-independent (HI) cultures of bd1971::kan compared with fliC1 merodiploid KnR HI control strain (Wild-Type for bd1971). The bd1971 mutant strain contains significantly more c-di-GMP than the control. Data are from 3 independent experiments.",
    "ncbi_link": "bd1971: 
fliC1: "
  },
  {
    "caption": "Relative levels of c-di-GMP in matched cell biomass wild-type predatory cultures of HD100 strain, silent Bd1971 deletion strain (Δ1971), Bd1971D306307A strain (bd1971DD) and Bd1971R67D strain (bd1971R). All mutant strains had higher levels of c-di-GMP compared to the wild type strain. Error bars show SEM. Data are from six independent experiments for HD100 and ΔBd1971 and from four independent experiments for Bd1971DD and Bd1971R mutants.",
    "ncbi_link": "Bd1971: "
  },
  {
    "caption": "Spot tests of co-transformants of either Bd0367 (DgcA; GGDEF protein) response regulator domain or Bd3125 (CdgA; a degenerate GGDEF protein likely involved in c-di-GMP binding and signalling) with full length Bd1971, or the N-terminal (1-145), or C-terminal (145-400) portions of Bd1971 in either pUT18c or pKT25 as indicated. Positive control was co-transformants with pUT18c-zip and pKT25-zip, negative control was the empty vectors. The co-transformants were plated on LB-X-Gal medium with positive interaction resulting in blue colouration, which can be seen for all of the interactions in both plasmid combinations, but not for the negative control. Images are representative of at least 4 independent experiments.",
    "ncbi_link": "Bd0367: 
Bd1971: 
Bd3125: "
  },
  {
    "caption": "A Heat map from RNA-Seq data from FACS-isolated muscle stem cells and single myofibers showing relative expression of Pax7, Myf5, MyoD, Myog and Myf6.",
    "ncbi_link": "Myf5: 17877
Myf6: 17878
MyoD: 17927
Myog: 17928
Pax7: 18509"
  },
  {
    "caption": "C-E Snapshots of the UCSC genome browser showing enrichment of Myf6 ChIP-Seq reads compared to control around EGF (C), LIF and OSM (D), and VEGFA (E) loci superimposed on reads for Histone H3 lysine 4 mono methyl (H3K4me1), Histone H3 lysine 4 tri methyl (H3K4me3) and total H3 in myoblasts (pink) and myotubes (green).",
    "ncbi_link": "EGF: 13645
LIF: 16878
OSM: 18413
VEGFA: 22339"
  },
  {
    "caption": "F Snapshots of representative IGV tracks displaying RNA-Seq data from WT whole muscle (WM), single myofibers (SF) and satellite cells (SC) showing the expression of EGF, EGFR and VEGFA. Ckm and Myf6 are used as positive controls for whole muscle and single fibers. PDGFRA, a marker of fibro/adipogenic progenitor cells, is used as a control to show the lack of niche cells in the single myofiber samples.",
    "ncbi_link": "PDGFRA: 
Ckm: 12715
EGF: 13645
EGFR: 13649
Myf6: 17878
VEGFA: 22339"
  },
  {
    "caption": "G-H RNA-Sequencing Reads Per Million (RPM) for EGF (G) and EGFR (H) in satellite cells and single myofibers. RNA-Sequencing libraries were prepared from 1000 satellite cells freshly-isolated by FACS or from a single myofiber as described in the Material and Methods. (n=3 biological replicates per group) bars=mean +/- SD, two-tailed t-test).",
    "ncbi_link": "EGF: 13645
EGFR: 13649"
  },
  {
    "caption": "K Depletion of Myf6 transcript by siRNAs in differentiated primary myotubes (5DM). (n=3 biological replicates), two-tailed t-test, bars = mean +/- SD L Depletion of Myf6 expression by siRNAs leads to a significant reduction in the gene expression output of Epidermal Growth Factor (EGF). (n=3 biological replicates), two-tailed t-test, bars = mean +/- SD",
    "ncbi_link": "EGF: 13645
Epidermal Growth Factor: 13645
Myf6: 17878"
  },
  {
    "caption": "B Picture of 8 week-old Myf6-KO and WT mice.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "C Relative expression of Myf6 transcript in the hindlimb skeletal muscles of Myf6-KO and WT mice measured by Quantitative Real-Time PCR (RT-qPCR) (n=4 mice). Boxes represent 1st and 3rd quartile, central line represents the median, whiskers represent the range, two-tailed t-test.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "D Color map of genes that are up/down regulated in the whole muscle transcriptome (RNA-Seq) of injured and uninjured hindlimb muscles from Myf6-KO and WT counterparts. Differential expression is Log2 transformed and truncated at +/-3. Color scale goes from blue (-3=lower than mean), to yellow (+3=higher than mean). E Heat map showing the distribution of Myf6 peaks within 100kb of the TSS of the myokine genes ranging from zero (black) to six ChIP-Seq peaks (red) occupancy.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "F Expression of EGF protein in the blood serum from Myf6-KO and heterozygous counterparts as measured by Enzyme-Linked Immunosorbent Assay (ELISA). (n=5 heterozygous biological replicates, n=3 Myf6-KO biological replicates), two-tailed t-test, error bars = +/- SD G Expression of VEGFA protein in the blood serum from Myf6-KO and heterozygous counterparts as measured by Enzyme-Linked Immunosorbent Assay (ELISA). (n=5 heterozygous biological replicates, n=3 Myf6-KO biological replicates), two-tailed t-test, error bars = +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "H Expression of VEGFA protein in the secretome of Myf6-KO and WT myotubes as measured by enzyme-linked immunosorbent assay (ELISA). Primary myotubes were derived from MuSCs isolated by Fluorescence Activated Cell Sorting (FACS, see the Extended Material and Methods) from Myf6-KO and WT mice. Myotubes were obtained by feeding >90% confluent primary myoblasts with differentiation media (DMEM supplemented with 5% horse serum) for seven days. Media from the last 48 hours of differentiation (days 5 to 7) was collected for ELISA secretome analysis. Protein readouts were normalized to the total number of nuclei in each plate. (n=4 WT biological replicates, n=3 Myf6-KO biological replicates), two-tailed t-test, error bars = +/- SD I Expression of EGF protein in the secretome of Myf6-KO and WT myotubes as measured by enzyme-linked immunosorbent assay (ELISA). Primary myotubes were derived from MuSCs isolated by Fluorescence Activated Cell Sorting (FACS, see the Extended Material and Methods) from Myf6-KO and WT mice. Myotubes were obtained by feeding >90% confluent primary myoblasts with differentiation media (DMEM supplemented with 5% horse serum) for seven days. Media from the last 48 hours of differentiation (days 5 to 7) was collected for ELISA secretome analysis. Protein readouts were normalized to the total number of nuclei in each plate. (n=4 WT biological replicates, n=3 Myf6-KO biological replicates), two-tailed t-test, error bars = +/- SD J Expression of EGF protein in the secretome of Myf6-HF expressing myotubes derived from Myf6-KO myoblasts (rescue) compared to Myf6-KO myotubes as measured by enzyme-linked immunosorbent assay (ELISA). Primary myotubes were derived from MuSCs isolated by Fluorescence Activated Cell Sorting (FACS, see the Extended Material and Methods) from Myf6-KO mice. Myotubes were obtained by feeding >90% confluent primary myoblasts with differentiation media (DMEM supplemented with 5% horse serum) for five days. Media from the last 48 hours of differentiation (days 3 to 5) was collected for ELISA secretome analysis. Protein readouts were normalized to the total number of nuclei in each plate. (n=3 Myf6-KO technical replicates, n=4 rescue technical replicates), two-tailed t-test, error bars = +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "K RT-qPCR of Myf6 expression in Myf6-KO (n=2 technical replicates), WT (n=3 biological replicates) and Myf6-HF (rescue) myotubes (n=3 technical replicates) (5DM). "Rescue" myotubes were generated from Myf6-KO myoblasts infected with a retrovirus containing Myf6-HF. two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "L-M RT-qPCR of EGF (L) and VEGFA (M) expression in Myf6-KO (n=5) and rescue (n=3-4) primary myotubes (5DM). two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "EGF: 13645
Myf6: 17878
VEGFA: 22339"
  },
  {
    "caption": "Immunofluorescence staining of WT (N) and Myf6-KO EDL (O) myofibers stained with PAX7, EGFR, and phospho-EGFR antibodies. Live fibers were maintained in culture media for 44 hours, followed by 4 hours of serum starving in non-supplemented DMEM. For treated samples, 40ng/ml of recombinant EGF was added to the non-supplemented DMEM for 10 minutes before fixation. Activation status of EGFR was assessed using antibodies against phospho-EGFR (pEGFR-Y1068). Scale bar=30μm P Quantification of the percentage of all pEGFR+/PAX7+ cells (defined as PAX7+ cells showing low or high pEGFR signal) on WT (n=24 fibers from n=3 mice) , Myf6-KO (n=22 fibers from n=3 mice) and Myf6-KO EDL myofibers treated with EGF (n=14 fibers from n=3 mice). two-tailed t-test, error bars = +/- SD Q Quantification of the percentage of EGFRhigh/PAX7+ cells (defined as PAX7+ cells showing high pEGFR signal) on WT (n=37 fibers from n=3 mice), Myf6-KO (n=34 fibers from n=3 mice) and Myf6-KO EDL myofibers treated with EGF (n=11 fibers from n=3 mice). two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "A Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and Laminin (LAMA1) antibodies at postnatal day 7. Arrowheads indicate PAX7+ satellite cells. Scale bar=200μm B Quantification of the number of PAX7+ cells per unit area (mm2) in TA muscle cross-sections from Myf6-KO and WT counterparts at postnatal day 7. (n=30 fields of view from n=3 animals), two-tailed t-test, error bars = +/- SD. C Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and Laminin (LAMA1) antibodies at postnatal day 21. Arrowheads indicate PAX7+ satellite cells. Scale bar=200μm D Quantification of the number of PAX7+ cells per unit area (mm2) in TA muscle cross-sections from Myf6-KO and WT counterparts at postnatal day 21. (n=27 fields of view from n=3 animals) , two tailed t-test, error bars = +/- SD). E Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and Laminin (LAMA1) antibodies at 3 months of age. Arrowheads indicate PAX7+ satellite cells. Scale bar=200μm F Quantification of the number of PAX7+ cells per unit area (mm2) in TA muscle cross-sections from Myf6-KO and WT counterparts at 3 months of age. (n=52 fields of view from n=5 animals), two tailed t-test, error bars = +/- SD. G Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and Laminin (LAMA1) antibodies at 10 months of age. Arrowheads indicate PAX7+ satellite cells. Scale bar=200μm H Quantification of the number of PAX7+ cells per unit area (mm2) in TA muscle cross-sections from Myf6-KO and WT counterparts at 10 months of age. (n=60 fields of view from n=3 animals), two tailed t-test, error bars = +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "Immunofluorescent analysis of myofiber-associated MuSCs isolated from the EDL muscles of 3 month-old Myf6-KO and WT counterparts. Fibers were stained with PAX7 antibody and counterstained with DAPI at time T=0 hours post fiber isolation. Scale bar=25μm J Quantification of the number of MuSCs per fiber between 3 month-old Myf6-KO (n=41 fibers from n=3 mice) and WT (n=31 fibers from n=3 mice) counterparts. Two-tailed t-test, error bars = +/- SD K Immunofluorescent analysis of myofiber-associated MuSCs isolated from the EDL muscles of 10 month-old Myf6-KO and WT counterparts. Fibers were stained with PAX7 antibody and counterstained with DAPI at time T=0 hours post fiber isolation. Scale bar=25μm L Quantification of the number of MuSCs per fiber between 10 month-old Myf6-KO (n=38 fibers from n=2 mice) and WT (n=67 fibers from n=3 mice) counterparts. Two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and KI67 antibodies at postnatal day 7. Scale bar=100μm, arrowheads highlight select MuSC B Quantification of the percentage of KI67+ over PAX7+ MuSCs between Myf6-KO and WT mice at postnatal day 7 (n=15 fields of view from n=3 animals) Two-tailed t-test, error bars = +/- SD. C Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and KI67 antibodies at postnatal day 21. Scale bar=100μm, arrowheads highlight select MuSC D Quantification of the percentage of KI67+ over PAX7+ MuSCs between Myf6-KO (n=28 fields of view from n=3 animals) and WT mice (n=31 fields of view from n=3 animals) at postnatal day 21. Two-tailed t-test, error bars = +/- SD E Immunofluorescent analysis of TA muscle cross-sections from Myf6-KO and WT mice with PAX7 and KI67 antibodies at 3 months of age. Scale bar=100μm, arrowheads highlight select MuSC F Quantification of the percentage of KI67+ over PAX7+ MuSCs between Myf6-KO and WT mice at 3 months of age (n=30 fields of view from n=5 mice). Two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "H (Left) Heat Map of up and down-regulated genes in the p38 MAPK pathway (WP400) in Myf6-KO and WT satellite cells. (Right) Gene set enrichment analysis of p38 MAPK pathway genes. In each plot, the blue curve represents the gene set enrichment score profile (Subramanian et al., 2005) across p38 MAPK pathway genes that are ranked by their differential expression. The grey curve represents the null expectation. P-values are based on permutation test (10,000 permutations).",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "Immunofluorescent analysis of WT and Myf6-KO primary myotubes cultured in differentiation media for 7 days and stained with MF20 and DAPI. Scale bar=200μm J Quantification of the fusion index between Myf6-KO (n=54 fields of view from n=3 mice) and WT (n=81 fields of view from n=4 mice) 7DM myotubes. Fusion index is calculated as the percentage of myonuclei out of the total number of nuclei per field of view. Two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "EDL myofibers isolated from WT and Myf6-KO mice fixed at time T=0 and stained with PAX7, MYOD and DAPI. Scale bar=30μm L Quantification of the percentage of MYOD+/PAX7+ satellite cells per fiber in Myf6-KO (n= 88 myofibers) vs WT (n= 86 myofibers) myofibers. Two-tailed t-test, error bars = +/- SD M Quantification of the average percentage of MYOD+/PAX7+ satellite cells per mouse in Myf6-KO and WT myofibers (n=3 mice). Two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "Staining for phospho-p38 MAPK on EDL myofibers cultured for 48 hours from Myf6-KO and WT mice. Scale bar=30μm O Quantification of the percentage of phospho-p38+/PAX7+ satellite cells per fiber in Myf6-KO (n=56 myofibers) vs WT (n=67 myofibers) myofibers. Two-tailed t-test, error bars = +/- SD P Quantification of the average percentage of phospho-p38+/PAX7+ satellite cells per mouse in Myf6-KO vs WT myofibers (n=3 mice). Two-tailed t-test, error bars = +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "B Representative images of bioluminescent signal from hindlimbs of Myf6-KO and WT counterparts at day 1, 7, 14, and 21 post transplantation. Scale bar=1cm",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "C Time course of average bioluminescent signal (total flux in radiance) in Myf6-KO and WT mice at 1, 7, 14 and 21 days post MuSC transplantation showing engraftment dynamics of donor MuSCs (mean across 4-5 animals per group ± SEM at each time point, two-tailed t-test).",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "D Bioluminescent signal (radiance) in Myf6-KO and WT mice at each time point normalized to the bioluminescent signal at day 1 post MuSC transplantation. (n=4-5 animals per group ± SD) two-tailed t-test, bars represent mean +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "E-F Immunostaining of TA cross-sections of injured muscle from 3 month-old WT (E) and Myf6-KO (F) mice stained with laminin (LAMA1) and PAX7 antibodies. Acute muscle injury was performed by injection of Cardiotoxin (CTX) into the TA muscle of Myf6-KO and WT mice (n=5 animals per group). Arrowheads indicate PAX7+ MuSCs. Scale bar=100μm G Quantification of the number of PAX7+ cells per unit area of TA muscle cross sections between Myf6-KO and WT mice (n= 5 animals per group) two-tailed t-test, bars represent mean +/- SD",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "H Immunofluorescent analysis of Myf6-KO and WT EDL myofibers cultured in growth media for 48 hours and stained with PAX7 and MYOD antibodies. Scale bar=20μm IQuantification of the number of PAX7+ MuSCs per fiber in Myf6-KO (n=27 fibers from n=3 mice) and WT (n=29 fibers from n=3 mice) mice after 48 hours in culture. Two-tailed t-test, error bars = +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "EdU staining of cultured primary myoblasts isolated by FACS (see materials and methods) from Myf6-KO and WT mice. Staining was analyzed after 6, 12 and 24 hours of EdU incorporation. Scale bar=100μm M Quantification of the percentage of EdU+ myoblasts after 6 hours (WT n=75 fields of view from n=3 mice, Myf6-KO n=72 fields of view from n=3 mice), 12 hours (WT n=82 fields of view from n=3 mice, Myf6-KOn=82 fields of view from n=3 mice), and 24 hours (WT n=70 fields of view from n=3 mice, Myf6-KO n=65 fields of view from n=3 mice) of EdU incorporation. Scale bar=100μm",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "Representative images of a co-culture assay between WT myotubes and either WT or Myf6-KO myoblasts. Briefly, WT myoblasts were differentiated for 2 days before adding equal numbers of either WT or Myf6-KO myoblasts for an additional 2 days, followed by immunostaining for MF20 and DAPI. Scale bar=400μm O Quantification of the average number of myoblasts per mm2 that have remained mononuclear after their addition to 2DM WT myotubes, for 2 additional days (n=3 biological replicates). Two-tailed t-test, bars represent mean +/- SD.",
    "ncbi_link": "Myf6: 17878"
  },
  {
    "caption": "(A) Detection of SARS-CoV-2 in nasopharyngeal swabs and peripheral blood using the GeneFinderTM COVID-19 Plus RealAmp Kit assay (ELITechGroup S.p.A., Turin, Italy). Three viral target genes, RdRp, N, and E, together with the housekeeping gene GAPDH were simultaneously amplified. Here the most sensitive target gene, N, is shown. Samples with Ct values > 40 were defined as negative. A dashed horizontal line indicates the cut-off. IL-6 values are shown in the same graph. Time of baricitinib treatment is highlighted (Patients A, B, and D for 10 days, Patient C for 12 days) with total time of evaluation on the X-axis. Fever and cough symptoms are indicated. The bars in grey indicate that cough has improved but has not resolved.",
    "ncbi_link": "GAPDH: 
RdRp: 
E: 43740570
N: 43740575"
  },
  {
    "caption": "A, B Relative gene expression is significantly increased for SARS-CoV-2 MA30 viral E gene (A; p < 0.0017) and interferon response ISG15  (B; p < 0.0044) in Saline  treated infected lung  extracts at 4 days follow up, when compared to uninfected mouse lungs. Data information:  Gene expression is normalized to GAPDH expression. Y axes vary dependent upon the detected relative expression  levels after normalizing data to the internal control. (ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1 treatments, green circle uninfected mice).",
    "ncbi_link": "E gene: 43740570
GAPDH: 14433
ISG15: 100038882"
  },
  {
    "caption": "Relative changes in gene expression for SARS-CoV-2  infections and associated modulation in inflammatory and coagulation responses are increased after   SARS-CoV-2 MA30 infection in lung  and heart  tissues (SARSCoV-2 MA30 infection - N = 18 mice  4 days follow up; N = 20 mice  7 days follow up; Uninfected mice  - N = 2). PEGSerp-1  treatment significantly modified gene expression for uPAR and complement pathways. C-L Inflammatory cytokines and growth factors are significantly increased with infection; IL-1 (C; p < 0.0003), IL-6 (D p < 0.0001),  IL-10 (E; p < 0.0001) ), TNF  (F; p < 0.0044), TGFb  (G; p < 0.0022) are increased with SARS-CoV-2 infection at 4 days follow up; with VEGF  the exception (H; p = 0.4695 ) Factors in the coagulation pathway, fX  (I; p < 0.0001), tPA  (J; p < 0.0382), and neuroserpin  (K; p = 0.1883 ) are also increased. None of these markers are modified by PEGSerp-1 treatments. Data information: Gene expression  is normalized to GAPDH expression. Y axes vary dependent upon the detected relative expression  levels after normalizing data to the internal control. (ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1 treatments, green circle uninfected mice).",
    "ncbi_link": "fX: 14058
GAPDH: 14433
IL-10: 16153
IL-1: 16176
IL-6: 16193
tPA: 18791
neuroserpin: 18787
TGFb: 21803
TNF: 21926
VEGF: 22339///22340"
  },
  {
    "caption": "Relative changes in  gene expression for SARS-CoV-2 infections and associated modulation in coagulation and immune responses are increased after  SARS-CoV-2 MA30 infection in lung  tissues (SARSCoV-2 MA30 infection - N = 18 mice  4 days follow up; N = 20 mice  7 days follow up; Uninfected mice  - N = 2). PEGSerp-1 treatment significantly modified gene expression  for uPAR  A-C Gene expression for  PEGserp-1 targets are increased after infection and modified by PEGSerp-1 treatments. uPA  (A; p = 0.3263), PAI-1 (B; p < 0.0001) and uPAR  (C; p < 0.0001) were increased in infected mouse lung  extracts at 4 days follow up when compared to uninfected lungs  with SARS-CoV-2  MA30 infection. PEG Serp-1 treatment produced a significant increase in uPAR  (C; p < 0.0157). Data information: N = 19 mice  at 4 days follow up; N = 20 mice  at 7 days follow up. ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1  treatments, green circle uninfected mice).",
    "ncbi_link": "uPA: 5328
uPAR: 18793
PAI-1: 18787"
  },
  {
    "caption": "Relative changes in gene expression for SARS-CoV-2 infections and associated modulation in coagulation and immune responses are increased after SARS-CoV-2 MA30  infection in lung  tissues (SARSCoV-2 MA30 infection - N = 18 mice  4 days follow up; N = 20 mice  7 days follow up; Uninfected mice  - N = 2). PEGSerp-1  treatment significantly modified gene expression  for complement pathways. D-F Complement pathways genes encoding C3  (D; p < 0.0021), C5  (E; p < 0.001) and C1INh  (F; p < 0.0008) were also significantly increased with infection. PEG Serp-1 treatment produced a borderline decrease in C5  (E; p = 0.0623) and a significant increase in C1Inh  (F; p < 0.0309). Data information: N = 19 mice  at 4 days follow up; N = 20 mice  at 7 days follow up. ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1 treatments, green circle uninfected mice).",
    "ncbi_link": "C3: 12266
C5: 15139
C1INh: 12258
C1Inh: 12258"
  },
  {
    "caption": "Relative changes in  gene expression for SARS-CoV-2 infections and associated modulation in coagulation and immune responses are increased after  SARS-CoV-2 MA30 infection in lung and heart  tissues (SARSCoV-2  MA30 infection - N = 18 mice  4 days follow up; N = 20 mice  7 days follow up; Uninfected mice  - N = 2). PEGSerp-1 treatment significantly modified gene expression  for complement pathways. G-I At 7 days follow up, relative gene expression  is no longer increased for C1Inh  with PEGSerp-1  treatment in MA30  infected mouse lungs  (G; p = 0.5956), but C1Inh  was significantly increased in myocardial  extracts with PEGSerp-1 treatment at 7 days (H; p < 0.0419). C5  was not significantly increased with infection (I; p = 0.1601) Data information: N = 19 mice  at 4 days follow up; N = 20 mice  at 7 days follow up. ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1 treatments, green circle uninfected mice).",
    "ncbi_link": "C5: 15139
C1Inh: 12258"
  },
  {
    "caption": "Relative changes in gene expression for SARS-CoV-2 infections and associated modulation in coagulation and immune responses are increased after SARS-CoV-2  MA30 infection in lung  and heart  tissues (SARSCoV-2 MA30  infection - N = 18 mice  4 days follow up; N = 20 mice  7 days follow up; Uninfected mice  - N = 2). PEGSerp-1  treatment significantly modified  gene expression for uPAR  J-L PAI-1 gene expression  was not increased in lung  extracts with  PEGSerp-1 treatment at 7 days follow up in MA30  infected mouse lungs  (J; p = 0.2403), but PAI-1 expression  was significantly increased at 7 days follow up in heart  extracts (K; p < 0.0454). uPAR  was not significantly increased in lung  extracts at 7 days follow up (p = 0.1514). A time course for  gene expression illustrates a peak time for changes in C1Inh gene expression demonstrates greater changes at 4 days when compared to day2 and day15 (L). Data information: N = 19 mice  at 4 days follow up; N = 20 mice  at 7 days follow up. ANOVA indicated by line at top with subgroup analyses below; infected mice  - blue circles Saline, red circle PEGSerp-1 treatments, green circle uninfected mice).",
    "ncbi_link": "uPAR: 18793
PAI-1: 18787
C1Inh: 12258"
  },
  {
    "caption": "(A) Bar graph showing qPCR  quantification of SEC61B  level in MCF10A MECs  ligated with rBM  in 2D  and 3D 12h post-plating (mean ± SEM; n=3 independent biological replicates). Statistical analysis by one-way ANOVA followed by Uncorrected Fisher's LSD, **P = 0.0022.",
    "ncbi_link": "SEC61B: 10952"
  },
  {
    "caption": "(F) Bar graph showing qPCR of the relative level of ATF3  mRNA in MCF10A MECs  ligated with rBM  in 2D  and 3D  12h post-plating (mean ± SEM; n=3 independent biological replicates). Statistical analysis by one-way ANOVA followed by Uncorrected Fisher's LSD, **P = 0.0037.",
    "ncbi_link": "ATF3: 467"
  },
  {
    "caption": "(H) Bar graph of qPCR  data measuring the relative levels of CRACR2B  mRNA in MCF10A MECs  ligated with rBM  in 2D  and 3D  12h post-plating (mean ± SEM; n=4 independent biological replicates). *P = 0.0371 (Student's t test).",
    "ncbi_link": "CRACR2B: 283229"
  },
  {
    "caption": "(C) Representative fluorescence microscopy images of MCF10A MECs  co-expressing the ER-plasma membrane contact site reporter GFP-MAPPER  and shRNA targeting filamin  (FLMN) or luciferase (Luc) ligated to rBM  in 2D  for 18h. Scale bar (whole cell), 10 μm; Scale bar (magnified), 2 μm.",
    "ncbi_link": "Luc: 
luciferase: 
filamin: 2316
FLMN: 2316"
  },
  {
    "caption": "(D) Quantification of the levels of GFP-MAPPER  at the  plasma membrane versus total cellular fluorescence in MCF10A MECs  stably expressing an shRNA targeting filamin  (FLMN) or luciferase  (Luc) ligated to rBM  in 2D (mean ± SEM; 2D + shLuc, n=38; 2D + shFLMN , n=39 cells from three independent experiments). **P < 0.0021 (Student's t test).",
    "ncbi_link": "Luc: 
luciferase: 
filamin: 2316
FLMN: 2316"
  },
  {
    "caption": "(E) Representative immunoblots  of filamin, phosphorylated EIF2a  (pEIF2a), total EIF2a  and  alpha-tubulin in cell lysate from MCF10A MECs  that express shRNA targeting filamin  (shFLMN) or luciferase  (shLuc) and ligated to a rBM  in 2D  or 3D  for 18h and corresponding quantification data (mean ± SEM; n=4 independent biological replicates). Statistical analysis by one-way ANOVA followed by Uncorrected Fisher's LSD. 2D-shLuc versus 3D-shLuc, ***P = 0.0003. 2D-shLuc versus 2D-shFLMN, ***P = 0.0004.",
    "ncbi_link": "Luc: 
luciferase: 
filamin: 2316
FLMN: 2316"
  },
  {
    "caption": "(F) Bar graph of the relative levels of ATF3  mRNA as measured by qPCR  in MCF10A MECs  expressing shRNA targeting filamin  (shFLMN) or luciferase  (shLuc) and ligated with rBM  in 2D  or 3D  for 18h (mean ± SEM; n=4 independent biological replicates). Statistical analysis by one-way ANOVA followed by Uncorrected Fisher's LSD. 2D-shLuc versus 3D-shLuc, ***P = 0.0005. 2D-shLuc versus 2D-shFLMN, *P = 0.0359.",
    "ncbi_link": "Luc: 
luciferase: 
ATF3: 467
filamin: 2316
FLMN: 2316"
  },
  {
    "caption": "(G) Representative immunoblots  of filamin, phosphorylated EIF2a  (pEIF2a), total EIF2a  and alpha-tubulin in cell lysate from MCF10A MECs  ligated to rBM  in 3D and treated with ethanol  (mock) or doxycycline  (FLMN) for 18h to induce filamin   expression and corresponding quantification data (mean ± SEM; n=5 independent biological replicates). **P = 0.0018 (Student's t test).",
    "ncbi_link": "FLMN: 2316"
  },
  {
    "caption": "(A) Schematic showing the principles behind  Atomic Force Microscopy  (AFM) (left). A cantilever at the end of the microscope probe is deflected when it is in contact with the cell surface. Cell cortex-mediated resistance to indentation alters the path of the laser beam focused on the cantilever that is then reflected onto a photodetector to enable measurement of cellular  cortical actin tension. AFM  was used to measure the  cortical actin tension in MCF10A MECs  ligated to a laminin-111  substrate in 2D  or 3D  (right) and treated with blebbistatin  (Bleb) to reduce cortical  actin  tension, induced to overexpress filamin  expression (FLMN), or activated ROCK  (ROCK) to increase  cortical actin tension. MECs  were indented using a 2-µm beaded tip on the AFM  cantilever and the Hertz model was used to fit each indentation curve to extract the Young's modulus of the cell cortex (mean ± SEM; 2D, n=123; 3D, n=184; 3D+FLMN, n=83; 2D+Bleb, n=66; 3D  + Bleb, n= 65; 3D+ROCK, n=212; n=AFM  indentation from >30 cells from three independent experiments). Statistical analysis by one-way ANOVA followed by Tukey's multiple comparisons test. 2D  versus 3D, ****P < 0.0001; 3D  versus 3D  + FLMN, ****P < 0.0001; 3D  versus 3D  + ROCK, ****P < 0.0001; 2D  versus 2D  + Bleb, ***P=0.0004.",
    "ncbi_link": "filamin: 2316///2317///2318
FLMN: 2316///2318///2317
ROCK: 282041"
  },
  {
    "caption": "(D) Schematic depicting strategy used to measure cortical  tension using  laser ablation. (Top) Cells with high cortical  tension exhibit plasma membrane blebbing  when cortical actin is severed by a pulsed laser, whereas cells with lower cortical  tension do not. (Bottom left) Bar graph of the laser ablation response of MCF10A MECs  ligated to a rBM  in 2D  or 3D  (mean ± SD; 2D, n= 35; 3D, n=40 cells from three independent experiments). (Bottom right) Bar graph showing the laser ablation response of MCF10A MECs  ligated to a rBM  in 2D or 3D  and treated in the absence or presence of blebbistatin  (2D+Bleb  and 3D+Bleb) or expressing constitutively active ROCK  (3D+ROCK) (mean; 2D, n= 14; 3D, n=15; 2D+Bleb, n=17; 3D+Bleb, n=14; 3D+ ROCK, n=10 cells from one experiment).",
    "ncbi_link": "ROCK: 282041"
  },
  {
    "caption": "(D) Bar graph of qPCR  data measuring the relative levels of ATF3  mRNA in MECs  ligated with rBM  in 2D and treated in the absence or presence of blebbistatin  (Bleb) (mean ± SEM; n=4 independent biological replicates). *P = 0.0158 (Student's t test).",
    "ncbi_link": "ATF3: 467"
  },
  {
    "caption": "(I) Representative line graph showing the changes in cytosolic  [Ca2+] levels of MCF10A MECs  in response to treatment. Fura-2-loaded MCF10A MECs  ligated with rBM  in 2D and expressing filamin  repeats 21-23 (2D+FLMNIg21-Ig23) or vector control (2D) were pre-incubated with EGTA  to chelate extracellular Ca2+ in the bath solution, challenged with 2 μM thapsigargin  to induce ER Ca2+ release, and replenished with 4 mM Ca2+ in bath solution at the indicated time. F340/F380 values of individual cells were quantified over the course of imaging (mean ± SD (2D, n=8; 2D + FLMNIg21-Ig23, n=7 cells from one experiment). (J) Quantification of the amplitude of the Ca2+ response (∆F=F-F0) induced by thapsigargin, where F0 is the basal fluorescence before thapsigargin  treatment. The data shown indicated mean ± SEM (2D, n=21; 2D + FLMNIg21-Ig23, n=19 cells from three independent experiments). ****P < 0.0001 (Student's t test).",
    "ncbi_link": "FLMN: 2317///2316///2318
FLMN: 2318///2316///2317
filamin: 2318///2317///2316"
  },
  {
    "caption": "(K) Bar graph of qPCR  data measuring the relative levels of ATF3  mRNA in MCF10A MECs  expressing luciferase  control or filamin  repeats 21-23 (FLMNIg21-Ig23) ligated with rBM  in 2D for 18h (mean ± SEM; n=3 independent biological replicates). *P = 0.032 (Student's t test).",
    "ncbi_link": "luciferase: 
ATF3: 467
filamin: 2316///2317///2318
FLMN: 2318///2316///2317"
  },
  {
    "caption": "(L) Representative immunoblots  of phosphorylated EIF2a  (pEIF2a), total EIF2a  and alpha-tubulin  in cell lysate from MCF10A MECs  expressing luciferase  (control) or filamin  repeats 21-23 (FLMNIg21-Ig23-myc) that were ligated with rBM  in 2D. Corresponding quantification data are shown at bottom (mean ± SEM; n=5 independent biological replicates). *P = 0.0112 (Student's t test).",
    "ncbi_link": "luciferase: 
myc: 
filamin: 2316///2317///2318
FLMN: 2317///2316///2318"
  },
  {
    "caption": "(A) Bar graph of qPCR  data measuring the levels of SEC61B  mRNA in MECs  ligated with rBM  in 2D and treated in the absence and presence of blebbistatin  (Bleb) (mean ± SEM; n=3 independent biological replicates). **P = 0.0046 (Student's t test).",
    "ncbi_link": "SEC61B: 10952"
  },
  {
    "caption": "(B) Bar graph of the percent cell death measured in MCF10A MECs  stably expressing shRNAs targeting Luciferase  (Luc), filamin (FLMN) or actinin  (ACTN) and ligated to rBM  in 2D. Cell death  was assessed at 48h post-plating via calcein AM  and ethidium homodimer staining  (mean ± SEM; n =3 independent biological replicates). **P = 0.0034; ns= not significant (Student's t test).",
    "ncbi_link": "Luc: 
Luciferase: 
actinin: 81
ACTN: 81
filamin: 2316
FLMN: 2316"
  },
  {
    "caption": "(C) Bar graph of the percent cell death in MCF10A MECs  expressing luciferase  control or filamin  repeats 21-23 (FLMNIg21-Ig23) that were ligated with rBM  in 2D. Cell death was assessed at 48h post-plating via calcein AM and ethidium homodimer staining  (mean ± SEM; n =3 independent biological replicates). *P = 0.0489 (Student's t test).",
    "ncbi_link": "luciferase: 
filamin: 2316///2317///2318
FLMN: 2316///2318///2317"
  },
  {
    "caption": "(D) Bar graph of the levels of endogenous Exo70  in MECs  stably expressing shRNA against Exo70  or luciferase  (Luc) (mean ± SEM; n =3 independent biological replicates). ** p = 0.0086.",
    "ncbi_link": "Luc: 
luciferase: 
Exo70: 23265"
  },
  {
    "caption": "(E) Bar graph of the percent cell death measured in MECs  expressing shRNA targeting Exo70  (shExo70) or luciferase  (control) and ligated with rBM  in 2D  or 3D. Cell death was assessed at 48h post-plating via calcein AM  and ethidium homodimer staining  (mean ± SEM; n=3 independent biological replicates). Statistical analysis by one-way ANOVA followed by Uncorrected Fisher's LSD. 2D  versus 3D, ***P = 0.0004. 3D + shLuc versus 3D  + shExo70, **P = 0.0091.",
    "ncbi_link": "Luc: 
luciferase: 
Exo70: 23265"
  },
  {
    "caption": "(F) Spheroids were induced to express constitutively active ROCK  or left uninduced (control) and co-stained with antibodies for laminin  or S100A14  (green), phalloidin  (red) and DAPI  (blue). Scale bar, 10 μm.",
    "ncbi_link": "ROCK: 282041"
  },
  {
    "caption": "(G) Representative immunoblots  of phosphorylated EIF2a  (pEIF2a), total EIF2a  and alpha-tubulin  in cell lysate from MCF10A MEC  spheroids induced to express constitutively active ROCK  or left uninduced (control). Corresponding quantification data are plotted at bottom (mean ± SEM; n=3 independent biological replicates). *P = 0.0442 (Student's t test).",
    "ncbi_link": "ROCK: 282041"
  },
  {
    "caption": "(H) Spheroids were induced to express constitutively active ROCK  or left uninduced (control), treated with Paclitaxel  (2nM), lysed and immunoblotted  for cleaved caspase-3  and alpha-tubulin  (top). In parallel, spheroids were stained  with antibody and phalloidin  to evaluate the levels of caspase-3 (green) and actin  organization (red), respectively. Scale bar, 10 μm.",
    "ncbi_link": "ROCK: 282041"
  },
  {
    "caption": "(I) Bar graph of the relative mRNA levels of ER  stress response genes including ATF3, STC2, PPP1R15A, and PMAIP1  in microarray  analyses of TRAIL  treated HMT-3522 S-1 MECs plated as monolayers  on a rigid rBM  (2D) or as spheroids  (3D) (mean ± SEM; n=3 independent experiments). ATF3, ***P = 0.0006; STC2, *P = 0.0353; PPP1R15A, *P = 0.0254; PMAIP1, *P = 0.0127 (Student's t test).",
    "ncbi_link": "ATF3: 467
PMAIP1: 5366
PPP1R15A: 23645
STC2: 8614"
  },
  {
    "caption": "B Endogenous USP45 was immunoprecipitated (IP) from wild‐type (WT) and USP45 knockout (KO) KBM7 cells lines. The immunoprecipitates were resolved on a polyacrylamide gel and stained with Instant Blue. The gel was divided into the indicated sections, and proteins identified by mass spectrometry are detailed in Supplementary Table S1. The key proteins that we focus on in this study are indicated.",
    "ncbi_link": "USP45: 85015
USP45: Q70EL2///85015"
  },
  {
    "caption": "C Yeast two‐hybrid (Y2H) assays were performed with a GAL4 DNA‐binding domain fusion and/or activation domain for each protein indicated in the table to detect interaction between these proteins. Cells grown on media lacking LEU, TRP and HIS (to select for bait and prey plasmids) or tested for lacZ reporter gene activity.",
    "ncbi_link": "GAL4: 
lacZ: "
  },
  {
    "caption": "D, E Endogenous SLX4 and ERCC1 were immunoprecipitated from extracts of WT or ERCC1 KO MEFs (D), or WT or SLX4 KO MEFs (E) and subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "SLX4: 52864"
  },
  {
    "caption": "C, D HEK293 cells were transiently transfected with constructs expressing the indicated wild‐type or mutant GFP-USP45 [1-62] fragment (C) or GFP full‐length USP45 (D) or empty GFP (C and D) as a control and processed as described in (A). LICOR-Odyssey quantitation of results shown in (C) is shown in Supplementary Fig S4.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "C USP45 KO U2OS cells were transiently transfected with a construct encoding FLAG‐ERCC1. Thirty‐six hours post‐transfection cells were treated with lactacystin (5 μM) for 6 h and lysed with a buffer containing 0.1 M N‐ethylmaleimide. Flag‐ERCC1 was immunoprecipitated and treated in the absence or presence of 0.1 μg of recombinant USP45 wild‐type (WT), non‐ERCC1‐binding USP45 [Asp25Ala, Glu26Ala] (AA) or catalytically inactive USP45 [Cys199Ala] (CA) for 1 h. The reactions were terminated by addition of sample buffer and analysed by immunoblot and Coomassie staining. Similar results were obtained in at least two separate experiments.",
    "ncbi_link": "ERCC1: 2067
USP45: 85015"
  },
  {
    "caption": "A Clonogenic survival assays were carried out in wild‐type (WT), USP45 knockout (KO) or USP45 KO cells re‐expressing wild‐type USP45 (RESWT) or catalytically inactive USP45 [Cys199Ala] (RESCA). The cells were treated with the indicated doses of mitomycin C (MMC) 16 h. Medium was changed and number of colonies quantified after 10 days. Each data point is the average of 3 experiments undertaken with 6 replicates ± SD.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "C, D As above, except rescue experiments are undertaken using the non‐ERCC1‐binding USP45 [Asp25Ala, Glu26Ala] mutant.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "A Wild‐type (WT), USP45 knockout (KO) or USP45 KO cells re‐expressing wild‐type USP45 (RESWT) or catalytically inactive USP45 [Cys199Ala] (RESCA) were used to analyse ERCC1 foci formation. Staining and analysis of endogenous ERCC1 foci formation was undertaken before (left panel), or after DNA damage induction by mitomycin C (40 ng/ml, 16 h, middle panel) or UV (20 J/m2 followed by 3‐h recovery, right panel). Three independent experiments were performed in which 500 cells per experiment were analysed. Scale bar, 10 μm.B Proportion of cells displaying more than 10 endogenous ERCC1 foci were quantified. Three independent experiments were performed in which 500 cells per experiment were analysed. Results are the mean of 3 experiments ± SD.C The wild‐type and USP45 knockout U2OS cells were treated with mitomycin C (40 ng/ml, 16 h) and total number of ERCC1 staining foci per cell was quantified in at least 50 independent cells at the indicated times. Similar results were obtained in two separate experiments. The data are presented as the average number of ERCC1 staining foci per cell.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "A Representative immunofluorescence microscopy images of endogenous wild‐type (WT) and USP45 knockout (KO) U2OS cells treated with no drug, BrdU (10 μM, 24 h), psoralen or angelicin (25 μM, 3 h). Cells were fixed 10 min after laser micro‐irradiation and stained for localisation of endogenous USP45, phosphorylated γ‐H2AX and DAPI. The right‐hand panel shows magnification of one micro‐irradiated cell. Similar results were obtained in at least three independent experiments. Scale bar, 10 μm.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "A U2OS cells were transiently transfected with the GFP-USP45 or GFP alone. Thirty‐six hours post‐transfection cells were irradiated with UV‐C (150 J/m2) through a micropore filter (lower panels) or left untreated (upper panels). Five minutes post‐irradiation, cells were fixed and co‐immunostained with antibodies recognising cyclobutane pyrimidine dimer (CPD) DNA lesions and GFP. The white arrows indicate co‐localisation between GFP-USP45 and CPD. Scale bar, 10 μm.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "B U2OS wild‐type (WT) and USP45 knockout (KO) cells were irradiated with UV‐C (20 J/m2). At the indicated post‐irradiation times, genomic DNA was extracted and subjected to Southern dot blot analysis using antibodies recognising CPD and dsDNA total antibody. Data are shown from a triplicate experiment in which each blot is derived from independent cells.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "A Live‐cell fluorescence microscopy analysis of U2OS cells stably expressing either GFPNLS empty, wild‐type (WT) USP45 or catalytically inactive USP45 [Cys199Ala]. Cells were treated with BrdU (10 μM, 24 h), psoralen or angelicin (25 μM, 3 h) and images captured at the indicated times after laser micro‐irradiation. The location of the micro‐irradiation stripe in each cell is indicated with a yellow line. Similar results were obtained in at least two independent experiments. Scale bar, 10 μm.",
    "ncbi_link": "USP45: 85015"
  },
  {
    "caption": "(D) Mean current responses to rapid switching from 140 mM CholGluc to 140 mM KGluc of HEK293T cells expressing WT EAAT1 (n=3) or WT EAAT2 (n=3). Cells were intracellularly dialyzed with a 115mM KGluc-based solution and held at 0 mV.",
    "ncbi_link": "EAAT2: 6506
EAAT1: 6507"
  },
  {
    "caption": "(D) Representative whole-cell current recordings from cells internally dialyzed with NaNO3 and glutamate in choline-NO3-based external solutions or in NaNO3-based solutions supplemented with 1 mM L-glutamate. Glutamate-induced changes in anion current amplitudes indicate that D399N and D486N EAAT2 (GltPh D312 and D405) are K+-independent, but are functionally expressed in the plasma membrane.",
    "ncbi_link": "EAAT2: 6506"
  },
  {
    "caption": "(E) Representative transport current recordings from cells expressing L448A or L448T (GltPh A360) or WT EAAT1 upon voltage jumps to ˗140 mV before and after superfusion with 1 mM l-glutamate. Cells were intracellularly dialyzed with a K+-free solution without permeating anions to isolate K+-independent transport currents. Transient capacitive currents during the first 5 ms after a voltage jump were blanked.",
    "ncbi_link": "EAAT1: 6507"
  },
  {
    "caption": "(F) Current-voltage relationship for net transport current amplitudes for WT and L448A/T EAAT1 (GltPh A360) for choline-based pipette solutions. Values are given as mean ± SD with indicated numbers of experiments.",
    "ncbi_link": "EAAT1: 6507"
  },
  {
    "caption": "(G) Time-dependent changes in L448A EAAT1 (GltPh A360) uptake currents during two repetitive glutamate applications and subsequent removals. Current amplitudes were measured at the end of voltage jumps to -140mV and plotted versus the time. Glutamate application is indicated by green bars. Values are given as mean ± SD of the last 100 data points in the current trace.",
    "ncbi_link": "EAAT1: 6507"
  },
  {
    "caption": "(H) Net transport current amplitudes for WT and L448A/T EAAT1 (GltPh A360) for different pipette solutions, Values are given as mean ± SD with indicated numbers of experiments (***, p<0.001 Student's t-test).",
    "ncbi_link": "EAAT1: 6507"
  },
  {
    "caption": "(E) Representative transport current recordings from a cell expressing R478A EAAT2 (GltPh R397) in the absence of internal K+. Transport currents were elicited by voltage jumps to -140mV before and after superfusion with 5 mM l-serine. Transient capacitive currents during the first 5 ms after a voltage jump were blanked.",
    "ncbi_link": "EAAT2: 6506"
  },
  {
    "caption": "(F) Time-dependent changes in steady-state R478A EAAT2 (GltPh R397) uptake currents during two consecutive serine applications and subsequent removals. Current amplitudes were measured at the end of voltage jumps to -140mV and plotted versus time. Serine application is indicated by green bars. Values are given as mean ± SD of the last 100 data points in the current trace.",
    "ncbi_link": "EAAT2: 6506"
  },
  {
    "caption": "(G) Current-voltage relationship for mean net transport currents for R478A EAAT2 induced by 5 mM l-serine for different intracellular solutions. Values are given as mean ± SD for the indicated number of experiments.",
    "ncbi_link": "EAAT2: 6506"
  },
  {
    "caption": "(H) Mean net transport currents for WT and R478A EAAT2 (GltPh R397) induced by 5 mM l-serine for different intracellular solutions. Values are given as mean ± SD for the indicated number of experiments.",
    "ncbi_link": "EAAT2: 6506"
  },
  {
    "caption": "High-resolution imaging of mitochondria in live cells using the Airyscan module of Zeiss LSM880 confocal microscope. H1975 cells transduced with matrix-targeted-DsRed and stained with NAO. Matrix-targeted Ds-Red differentiates matrix from cristae stained with NAO. Arrowheads point to cristae. Scale bar = 500 nm. N = 1 independent experiment.",
    "ncbi_link": "DsRed: "
  },
  {
    "caption": "High-resolution imaging of mitochondria in live cells using the Airyscan module of Zeiss LSM880 confocal microscope. The structure of the IMM in Mic13-KO cells (HeLa), stained with NAO. The number of cristae is decreased in Mic13-KO compared to control cells shown in panel A, labeled with arrowheads. Scale bar = 500 nm. N = 3 independent experiments.",
    "ncbi_link": "Mic13: 125988"
  },
  {
    "caption": "High-resolution imaging of mitochondria in live cells using the Airyscan module of Zeiss LSM880 confocal microscope. Live-cell imaging of the IMM in control and PTPMT1 KD H1975 cells, a model of cardiolipin deficiency. A gallery of mitochondria from various control H1975 cells expressing scrambled shRNA and stained with NAO, showing cristae (arrowheads). Scale bars = 500 nm. N = 3 independent experiments. A gallery of mitochondria from various H1975 cells expressing PTPMT1 shRNA and stained with NAO. Note the derangement of the ultrastructure (arrowheads). Scale bars = 500 nm. N = 3 independent experiments.",
    "ncbi_link": "PTPMT1: 114971"
  },
  {
    "caption": "The role of cristae structure as well as CJ formation and sealing on the generation of the difference in ΔΨm between cristae and IBM were studied Representative images of mitochondria in control (top row) vs. Mic13-KO (bottom row) HeLa cells. Note that TMRE FI in Mic13-KO mitochondria is distributed more evenly along the IMM, so that ΔΨCr-IBM is decreased. Scale bar = 500 nm. N = 3 independent experiments. Quantification of A, showing deletion of Mic13 in HeLa cells results in significant decrease in ΔΨCr-IBM. While Mic13-KO cells show a substantial decrease in cristae number, the loss of cristae does not appear absolute, making it feasible to compare TMRE FI at cristae relative to IBM. N = 3 independent experiments.",
    "ncbi_link": "Mic13: 125988"
  },
  {
    "caption": "The role of cristae structure as well as CJ formation and sealing on the generation of the difference in ΔΨm between cristae and IBM were studied by disrupting cristae using Mic10- and Mic60-deficient cells. Mic60 support cristae formation. Mic10 is essential for CJ formation, and, in its absence, cristae tend to remain as vesicles detached from IBM. Live-cell Airyscan imaging of TMRE was used in all figure panels and models. Representative images of Hap1 control (top row) vs. Mic60 KO (middle row) and Mic10 KO (bottom row); Mic60-KO mitochondria show very few cristae structures. TMRE staining along the IMM is relatively homogeneous, indicating decreased ΔΨCr-IBM. In general, Mic10 KO in Hap1 cells results in decreased TMRE signal intensity at cristae relative to IBM (arrowheads) as compared to control cells. Deletion of Mic10 induces detachment of cristae from IBM (see Figure 8). Except for the detached cristae vesicles, the TMRE staining is homogeneously distributed n Mic10-KO cells, indicating decreased ΔΨCr-IBM. Scale bar = 500 nm. N = 3 independent experiments. Quantification of C, showing Mic60 KO in Hap1 cells results in significant decrease in ΔΨCr-IBM. While Mic60-KO cells show a marked loss of normal cristae structures, depletion of cristae does not appear absolute, making it possible to compare TMRE FI at cristae relative to IBM. N = 3 independent experiments. Quantification of C, showing Mic10 KO in Hap1 cells results in a significant decrease in ΔΨCr-IBM. Note: quantification of ΔΨm at cristae relative to IBM was performed only on cristae structures that appeared to maintain attachment to IBM. N = 3 independent experiments.",
    "ncbi_link": "Mic60: 10989
Mic10: 440574"
  },
  {
    "caption": "Studies show that Opa1 interacts with MICOS complex, promoting closure of CJs. Thus, we tested whether Opa1 was required to maintain the difference in ΔΨm between cristae and IBM. Live-cell Airyscan images of MEF control (top row) vs. Opa1 KO (bottom row), co-stained with NAO and TMRE. Arrowheads indicate decreased intensity of TMRE FI at cristae compared to IBM. Note the more even distribution of TMRE staining, indicating the cristae and IBM are relatively equipotential. Scale bar = 500 nm. Quantification of G, showing Opa1-KO MEFs have significantly decreased ΔΨCr-IBM. N = 3 independent experiments.",
    "ncbi_link": "Opa1: 74143"
  },
  {
    "caption": "Live-cell Airyscan images of laser-induced depolarization time series of Mic10 KO Hap1 cell stained with TMRE. Mitochondrion exposed to rapid, high 2-photon laser power in region of white box, arrow (~0.3 sec); large, hyperpolarized vesicle (arrowhead) remains polarized after the rest of the mitochondrion loses ΔΨm, indicating electrochemical discontinuity between hyperpolarized vesicles and the rest of the mitochondrion, including the IBM. Scale bar = 500 nm. N = 2 independent experiments.",
    "ncbi_link": "Mic10: 440574"
  },
  {
    "caption": "Live-cell Airyscan image of time series showing hyperpolarized vesicles (arrowheads; region cropped from dashed white box) inside mitochondria lacking both Opa1 and Drp1. Scale bar = 500 nm. N = 2 independent experiments. Free movement of hyperpolarized vesicles within the matrix indicate their detachment from the IBM, representing an extreme case of cristae independency within one mitochondrion (see Movie EV 1 for time series).",
    "ncbi_link": "Drp1: 74006
Opa1: 74143"
  },
  {
    "caption": "A. Mutations in the kinase motif abolished the yeast toxicity of MavQ. S. cerevisiae was transformed with plasmids expressing Flag-tagged wild-type MavQ or the indicated MavQ mutants under the galactose-inducible promoter. Yeast cells were spotted on synthetic medium supplemented with glucose or galactose for 3 days before image acquisition.",
    "ncbi_link": "Flag: 
MavQ: 57036982"
  },
  {
    "caption": "A. Representative immunofluorescence images of the association of MavQ with the LCV. BMDM cells infected with wild-type or Dot/Icm-deficient (dotA-) L. pneumophila were sequentially stained with antibodies against L. pneumophila and MavQ. Images were taken under a fluorescence microscope. Insets represent 3x magnification of regions defined by dash lines. Scale bar, 5 μm.",
    "ncbi_link": "dotA: 57036686"
  },
  {
    "caption": "D. Co-expression of SidP with MavQ in HeLa cells does not influence the production of PtdIns3P caused by MavQ. The association of the fluorescence probe GFP-2xFYVEHrs with vesicle-like structures was used to indicate the distribution of PtdIns3P in cells. At least 100 cells were scored in each sample (n≥100) (left panel). Wort, wortmannin. Expression of MavQ and SidP in the samples were shown in the right panel. EV represents empty vector.",
    "ncbi_link": "SidP: 
MavQ: 57036982"
  },
  {
    "caption": "E. Deletion of sidP does not impact the association of SidC with the LCV. BMDMs infected with the indicated L. pneumophila stains were stained and the association of SidC with bacterial phagosomes was similarly determined (n≥100) (left panel). Representative images of infected cells harboring bacterial phagosomes were also shown (right panel). Insets represent 3x magnification of regions defined by dash lines. Scale bar, 5 μm.",
    "ncbi_link": "sidP: "
  },
  {
    "caption": "c, MSN cultures at DIV11 were treated for 2h with either 10 µM of the D1-agonist SKF-38393 (SKF) alone or with SKF and 10 µM of the selective D1-antagonist SCH-23390 (SCH). qPCR was performed to determine the relative mRNA levels of the immediate early genes cFos  and Arc. Mean + SEM; one-way ANOVA with Holm-Sidak post-hoc correction; p** < 0.01, p**** < 0.0001; n = 3 independent cultures as biological replicates.",
    "ncbi_link": "Arc: 11838
cFos: 14281"
  },
  {
    "caption": "g, Differential induction of Npas4 through HiK and not forskolin in hiPSC-derived forebrain organoids. Organoids were treated with HiK (55 mM) or the PKA activator forskolin plus TTX  (Fsk, 10 µM; TTX  1 µM) for 1h before  qPCR analysis was performed to assess mRNA levels of Npas4  and Arc. Mean + SEM; n = 7  organoids in control condition, n = 5 organoids for  HiK, n = 5 organoids for  Fsk/TTX. One-way ANOVA with Tukey's post-hoc test, ns = not significant, p* < 0.05, p***<0.001.",
    "ncbi_link": "Arc: 23237
Npas4: 266743"
  },
  {
    "caption": "MSN cultures were stimulated with HiK (55 mM) for 1h in the presence of various pharmacologicals to dissect the  synapse-to-nucleus cascades mediating transcription of Npas4, Fosb  and Arc. Values were normalized to the induced condition to compare for differences in induction between treatments. Mean + SEM and one-way ANOVA with Bonferroni post-hoc correction were used in all experiments. p* < 0.05, p** < 0.01, p***<0.001, p****<0.0001. n-number indicated in each panel. a, co-incubation with the NMDA receptor blocker APV  (100 mM, applied 5min before) reveals that all IEG inductions through HiK in  MSNs depend on NDMA receptor   activity. Mean + SEM; n = 4 independent cultures as biological replicates. b, blockade of voltage-dependent calcium channels through verapamil (30 µM, 5min before) and  TTX  (1 µM, 5min, to prevent verapamil-induced bursting) leads to significant reduction in gene-inductions for Npas4 and Fosb. Mean + SEM; n =4 independent cultures as biological replicates. c, inhibition of ERK1/2 through  UO126 (10 µM, 20min before) leads to significant blockade of mRNA induction for Arc and Fosb, but not Npas4. Mean + SEM; n = 3 independent cultures as biological replicates. d, inhibition of p38alpha and  p38beta through SB203580 or SB202190 respectively (both 10 µM and 20min before) leads to significant reductions in mRNA induction for Arc and Fosb, but not Npas4. Mean + SEM; n = 3 independent cultures as biological replicates. e, blockade of PKA activity through H-89  (10 µM, 20min before) leads to reduced induction of Arc, unaffected induction of Fosb  and a superinduction of Npas4. Mean + SEM; n = 3 independent cultures as biological replicates. f, inhibition of calcineurin through co-application of Cyclosporin and FK506 (1 µM each, 20min before) leads to unaffected induction of mRNAs for Arc and Fosb, but significantly reduced levels of Npas4. Mean + SEM; n = 3 independent cultures as biological replicates.",
    "ncbi_link": "Arc: 11838
Fosb: 14282
Npas4: 225872"
  },
  {
    "caption": "MSN  cultures were stimulated with  HiK (55 mM) for 1h in the presence of various pharmacologicals to dissect the synapse-to-nucleus cascades mediating transcription of  Npas4, Fosb  and Arc. Values were normalized to the induced condition to compare for differences in induction between treatments. Mean + SEM and one-way ANOVA with Bonferroni post-hoc correction were used in all experiments. p* < 0.05, p** < 0.01, p***<0.001, p****<0.0001. n-number indicated in each panel. g, blockade of  CaMKII/IV through application of KN-93  (1 µM, 20min before) leads to significantly reduced mRNA inductions of Arc, Fosb and Npas4. Mean + SEM; n = 4 independent cultures as biological replicates. h, co-application of HiK and SKF reveals synergistic effects on mRNA induction of Fosb but not Arc  or Npas4, Mean + SEM; n = 6 independent cultures as biological replicates. ",
    "ncbi_link": "Arc: 11838
Fosb: 14282
Npas4: 225872"
  },
  {
    "caption": "investigating the role of  nuclear calcium signaling in mRNA induction of Arc, Fosb and Npas4. k,  immunohistochemical analysis  of MSNs infected with mCherry-NLS as control or the competitive  nuclear Ca2+/CaM antagonist CaMBP4-mCherry. Infection on DIV4, fixation on DIV11. D32 = anti-Darpp-32. scale bar = 10 µm. l, MSNs expressing rAAV-mCherry-control or CaMBP4   (BP4) were treated with 55mM HiK for 1h and qPCR analysis was performed for the indicated IEGs. Mean + SEM; two-way ANOVA with Bonferroni post-hoc test, ns = not significant, p****<0.0001. n = 5 independent cultures as biological replicates. m, immunohistochemical analysis of MSNs infected with mCherry-NLS as control or the nuclear Ca2+-buffer Parvalbumin-NLS-mCherry. Infection on DIV4, fixation on DIV11. D32 = anti-Darpp-32. n, MSNs expressing rAAV-mCherry-control or PV-NLS were treated with 55mM HiK  for 1h and  qPCR analysis was performed for the indicated IEGs. Mean + SEM; two-way ANOVA with Bonferroni post-hoc test, p* < 0.05, p** < 0.01, p****<0.0001. n = 3 independent cultures as biological replicates.",
    "ncbi_link": "mCherry: 
Arc: 11838
BP4: 12326
CaMBP4: 12326
Fosb: 14282
Npas4: 225872
PV: 19293"
  },
  {
    "caption": "e, Npas4  controls activity-dependent upregulation of genes for glutamatergic synapse  formation and  Ca2+ channels. MSNs were infected with rAAVs expressing shRNA-scrambled (control) or shNpas4 (Npas4 knockdown) on DIV5. On DIV 12, cultures were stimulated with HiK (55 mM) for 1h or 6h and mRNA levels were analysed by qPCR. mRNA level = fold change in mRNA compared to shscrambled unstimulated control. Mean + SEM; two-way ANOVA with Bonferroni post-hoc test, p* < 0.05, p***<0.001. n = 5 independent cultures as biological replicates.",
    "ncbi_link": "Npas4: 225872"
  },
  {
    "caption": "e, Confocal images of  tdTomato-labelled D1-MSNs expressing shscr-GFP or shNpas4-GFP (left panels; scale bar: 20 µm). 3D volume-renderings of MSN dendrites  from the NAc shell (right panels; scale bar: 2 µm).",
    "ncbi_link": "GFP: 
Npas4: 225872"
  },
  {
    "caption": "g, Confocal images of tdTomato-labelled  D2-MSNs expressing shscr-GFP or shNpas4-GFP (left panels; scale bar: 20 µm). 3D volume-renderings of MSN dendrites from the NAc shell (right panels; scale bar: 2 µm).",
    "ncbi_link": "GFP: 
Npas4: 225872"
  },
  {
    "caption": "a-d, Scatter plot of passive and active  membrane  properties of MSNs in ex vivo slice preparations from shRNA-AAV-infected  mice, plotted for MSNs as D1-positive (D1+), D1-negative (D1-) and those two populations pooled (all). a, rheobase; mean ± SEM. b, firing rate  estimated at twice the value of the rheobase; mean ± SEM. c, input/output gain values recorded in shscr- or shNpas4-injected mice, mean ± SEM. The increased rheobase  and lower input-output gain indicate a lower excitability for MSNs in the  Npas4-knockdown group. d, facilitation at corticostriatal synapses examined in  MSNs with paired-pulse stimulation at 20 and 4 Hz. Representative current traces and scatter plots of paired-pulse experiments illustrate a potent facilitation in MSNs in mice  injected with scr-shRNA and a significant decrease of the facilitation in mice injected with shNpas4, with a stronger effect in D1-negative MSNs. Mean ± SEM. Data information: For n-numbers, please see Table EV1. Mann-Whitney-Test, p*<0.05, p**<0.01. ",
    "ncbi_link": "Npas4: 225872"
  },
  {
    "caption": "b, cocaine-induced hyperlocomotion is attenuated by Npas4-knockdown while locomotor behaviour after saline injection is unaffected on all days. Mean + SEM; two-way ANOVA followed by Bonferroni post hoc test. p* < 0.05, p** < 0.01, ns = not significant. n = 12 - 16 animals per condition.",
    "ncbi_link": "Npas4: 225872"
  },
  {
    "caption": "E Irf1  expression in human blastocysts. Integrated  single cell RNA-seq  data from blastocysts  collected at or cultured to indicated time points. Data is derived from a total of 16 embryos  which passed quality control metrics.",
    "ncbi_link": "Irf1: 3659"
  },
  {
    "caption": "A Western Blot  analysis of  Irf1-/- in ESC  and EpiLC, probed with antibodies against IRF1  and VINCULIN  as loading control. Shown are two independent clonal cell lines.",
    "ncbi_link": "Irf1: 16362"
  },
  {
    "caption": "A. Genes involved in innate immunity are significantly upregulated in nuo-6 and isp-1 worms. Gene expression changes in the mitochondrial mutants were determined by RNA sequencing and compared to wild-type N2 worms. Results represent counts per million (CPM) expressed as a percentage of wild-type of six biological replicates per strain. Data information: Error bars indicate SEM. *p<0.05, **p<0.01, ***p<0.001. Statistical significance was determined using a one-way ANOVA with Dunnett's multiple comparison test",
    "ncbi_link": "isp-1: 177609
nuo-6: 172438"
  },
  {
    "caption": "B. Upregulation of innate immunity genes is dependent on the  p38-mediated innate immune signaling pathway including  NSY-1, SEK-1, PMK-1 and ATF-7. Gene expression changes were examined by quantitative RT-PCR of three biological replicates per strain. Data information: Error bars indicate SEM. *p<0.05, **p<0.01, ***p<0.001. Statistical significance was determined using a one-way ANOVA with Dunnett's multiple comparison test",
    "ncbi_link": "ATF-7: 175587
NSY-1: 24104671
PMK-1: 191743
SEK-1: 181043"
  },
  {
    "caption": "C. Using a fluorescent reporter strain for the innate immunity gene T24B8.5 confirms that innate immunity genes are upregulated in the long-lived mitochondrial  mutants and that components of the  p38-mediated innate immune signaling pathway are required for their upregulation. Scale bar indicates 250 µM. Three biological replicates per strain were quantified. Data information: Error bars indicate SEM. *p<0.05, **p<0.01, ***p<0.001. Statistical significance was determined using a two-way ANOVA with Bonferroni post-test",
    "ncbi_link": "T24B8.5: 188838"
  },
  {
    "caption": "A-D. Resistance to bacterial pathogens was tested by exposing  worms to Pseudomonas aeruginosa strain PA14 in a slow kill assay. Both  nuo-6 and isp-1  long-lived  mitochondrial  mutants show increased resistance compared to wild-type worms (A). Disruption of components of the  p38-mediated innate immune signaling pathway (nsy-1, sek-1, pmk-1, atf-7) markedly decreases resistance to PA14 in wild-type (B), nuo-6 (C) and isp-1 (D) worms. All strains were tested in a single parallel experiment. Two biological replicates per strain were performed with a total of at least 175 animals per strain. Data information: ***p<0.001. Statistical significance for survival plots was determined with the log-rank test. Significance is indicated between the strain listed on top and all other strains. Data from panel A is repeated in panels B, C, and D for direct comparison.",
    "ncbi_link": "atf-7: 175587
isp-1: 177609
nsy-1: 24104671
nuo-6: 172438
pmk-1: 191743
sek-1: 181043"
  },
  {
    "caption": "A-H. To examine the role of the  p38-mediated innate immune signaling pathway in the long-lifespan of the nuo-6 and  isp-1 mitochondrial  mutants, we crossed the long-lived mitochondrial mutants to  worms with mutations in nsy-1, sek-1, pmk-1  and atf-7(gof). In each case, mutation of genes involved in p38-mediated innate immunity signaling markedly reduces the lifespan of the long-lived  mitochondrial mutant but have little or no impact on wild-type  lifespan. In panel G, we utilized pmk-1 RNAi instead of the pmk-1  mutation because of the close proximity of isp-1 and pmk-1  on the same chromosome. EV indicates empty vector. The  lifespan results for panels A, B, D, E, F, and H were performed in a single parallel experiment. Results are from a minimum of three biological replicates per strain. Data information: Statistical significance for survival  plots was determined with the log-rank test. p-values indicate significance between red and purple lines. Control strains are shown in multiple panels for direct comparison. ",
    "ncbi_link": "atf-7: 175587
isp-1: 177609
nsy-1: 24104671
nuo-6: 172438
pmk-1: 191743
sek-1: 181043"
  },
  {
    "caption": "A,B. To determine the extent to which the  p38-mediated innate immunity pathway is activated in nuo-6 and isp-1 mutants, we measured the ratio of phosphorylated PMK-1/p38 to total PMK-1/p38 by  Western blotting. Representative blots are shown (A). There is no difference in the ratio of phosphorylated to total PMK-1/p38 in the long-lived mitochondrial  mutants compared to wild-type (B). Eight biological replicates of wild-type worms and nine of mitochondrial mutants were quantified. Data information: Error bars indicate SEM. ***p<0.001. NS = not significant. Statistical significance was assessed using a one-way ANOVA with Dunnett's multiple comparison test",
    "ncbi_link": "isp-1: 177609
nuo-6: 172438"
  },
  {
    "caption": "F. Constitutive activation of  atfs-1 is sufficient to decrease food consumption to the same level as in long-lived mitochondrial mutants. Three biological replicates per strain were measured, each including at least three technical replicates. atfs-1(lof) allele is gk3094, atfs-1(gof) allele is et17. Data information: Error bars indicate SEM. ***p<0.001. NS = not significant. Statistical significance was assessed using a one-way ANOVA with Dunnett's multiple comparison test ",
    "ncbi_link": "atfs-1: 179922"
  },
  {
    "caption": "A. A deletion of daf-16 completely abolishes the increased resistance to bacterial pathogens in isp-1  mutants. p-value indicates the significance of difference between red and purple lines. Three biological replicates per strain were performed. Data information: Statistical significance was assessed using log-rank test.",
    "ncbi_link": "daf-16: 172981
isp-1: 177609"
  },
  {
    "caption": "B,C. While daf-16 RNAi effectively decreases the expression of DAF-16 target genes (B, sod-3, dod-3, mtl-1, ftn-1, icl-1,  sodh-1), it does not affect the expression of any of the innate immunity genes (C, T24B8.5, K08D8.5, F55G11.8, clec-65, clec-67, dod-22, Y9C9A.8 and C32H11.4). This indicates that DAF-16 is not required for expression of innate immune signaling pathway target genes in isp-1 mutants. daf-16 expression was knocked down using RNAi beginning at the L4 stage of the parental generation. RNA was isolated from six biological replicates at the young adult stage of the experimental generation. RNA from the six biological replicates was pooled for RNA sequencing.",
    "ncbi_link": "C32H11.4: 178244
clec-65: 174928
clec-67: 177151
daf-16: 172981
DAF-16: 172981
dod-22: 178247
dod-3: 178737
F55G11.8: 186340
ftn-1: 179138
icl-1: 178583
isp-1: 177609
K08D8.5: 178243
mtl-1: 179060
sod-3: 181748
sodh-1: 179627
T24B8.5: 188838
Y9C9A.8: 177261"
  },
  {
    "caption": "A. To examine the role of the ATFS-1 transcription factor and the mitoUPR response in the enhanced bacterial pathogen resistance in nuo-6  mutants, we examined the effect of disrupting atfs-1 in nuo-6  mutants. Loss of  atfs-1  completely abolishes the increased resistance to bacterial pathogens in nuo-6 worms. p-value indicates significance of difference between red and purple lines. nuo-6;  atfs-1 contains the gk3094 deletion allele. Three biological replicates per strain were measured. B. To examine the role of ATFS-1 in the upregulation of innate immunity genes in nuo-6  mutants, we compared gene expression  between nuo-6 and nuo-6; atfs-1 mutants with wild-type worms and  atfs-1  mutants as controls. Deletion of atfs-1  significantly decreases the  expression  of genes involved in innate immunity in nuo-6 worms  but does not decrease the  expression  of these genes in wild-type worms. Gene expression changes were determined by RNA sequencing of six biological replicates of each genotype. Results represent counts per million (CPM) expressed as a percentage of wild-type. Worms in a wild-type background (control) are shown with white bars, while worms  with atfs-1 deletion are shown with blue bars. Data information: Error bars indicate SEM. **p<0.01, ***p<0.001. Statistical significance in panel A was assessed using log-rank test. Statistical significance in panel B was assessed using a two-way ANOVA with Bonferroni posttest. ",
    "ncbi_link": "atfs-1: 179922
ATFS-1: 179922
nuo-6: 172438"
  },
  {
    "caption": "A. Examination of mRNA levels of genes involved in innate immunity in two constitutively active  atfs-1  mutants (et15 and et17) revealed that innate immunity genes are upregulated when ATFS-1  is activated. This indicates that activation of the  mitoUPR can cause activation of genes that are regulated by the p38-mediated innate immune pathway. Gene expression changes were determined by RNA sequencing of six biological replicates of each genotype. Results represent counts per million (CPM) expressed as a percentage of wild-type. Data information: Error bars indicate SEM. *p<0.05 **p<0.01, ***p<0.001. NS = not significant. Statistical significance was assessed using a one-way ANOVA with Dunnett's multiple comparison test.",
    "ncbi_link": "atfs-1: 179922
ATFS-1: 179922"
  },
  {
    "caption": "Western blot analysis (B) of DCLK1  in aortas  of LFD  and HFD-fed ApoE-/- mice.  β-actin was used as the loading control (n=10 biological replicates).",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "(J-K) Protein (J) and mRNA (K) levels of inflammatory cytokines TNF-α and IL-6  in serum  and aortas. The values of mRNA levels were normalized to Rn18s  (n=10 biological replicates). Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "ncbi_link": "Rn18s: 19791"
  },
  {
    "caption": "(L) mRNA levels of proinflammatory chemokines and adhesion molecules in aortas  (n=10 biological replicates). The values were normalized to Rn18s. Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "ncbi_link": "Rn18s: 19791"
  },
  {
    "caption": "(A-B) Mouse primary peritoneal macrophages (MPMs) isolated from DCLK1f/f and  DCLK1MCKO mice  were challenged with oxLDL  (50 μg/mL) for 24 h. Protein levels of TNF-α  (A) and  IL-6 (B) were analyzed using ELISA  (n=3 biological replicates). Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "ncbi_link": "DCLK1: 13175"
  },
  {
    "caption": "(C-D) MPMs  isolated from DCLK1f/f and DCLK1MCKO mice  were challenged with oxLDL (50 μg/mL) for 6 h. mRNA levels of Tnf-α  (C) and  Il-6 (D) were determined via RT-qPCR (n=3 biological replicates). The values were normalized to β-actin. Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "ncbi_link": "β-actin: 11461
DCLK1: 13175
Il-6: 16193
Tnf-α: 21926"
  },
  {
    "caption": "(B) 293T  cells were transfected with Flag-DCLK1  plasmid for 24 h. Control cells were transfected with empty vector (EV). Levels of Flag  were measured by Western blot (n=3 biological replicates). Data information: Data were shown as mean ± SEM; *, P < 0.05; ns, not significant, two-tailed unpaired Student's t-test.",
    "ncbi_link": "Flag: 
DCLK1: 9201"
  },
  {
    "caption": "(D) Co-immunoprecipitation of DCLK1  and IKKβ  in 293T  cells transfected with Flag-DCLK1. Flag-DCLK1  was immunoprecipitated  by anti-Flag  antibody. IgG, immunoglobulin G. (E) Co-immunoprecipitation of DCLK1  and IKKβ  in MPMs  challenged with oxLDL  (50 μg/mL) for 1 h. DCLK1  was immunoprecipitated  by anti-DCLK1  antibody.",
    "ncbi_link": "Flag: 
DCLK1: 9201"
  },
  {
    "caption": "293T  cells were co-transfected with Flag-DCLK1  and si-IKKβ  for 24 h. Western blot analysis (H) of IκBα, p-IKKβ  and p-p65. GAPDH, IKKβ  and p65  were used as loading controls (n=3 biological replicates).",
    "ncbi_link": "Flag: 
DCLK1: 9201
IKKβ: 3551"
  },
  {
    "caption": "(K-N) Protein (K-L) and mRNA (M-N) levels of inflammatory cytokines TNF-α  and IL-6 in serum  and aortas. The values of mRNA levels were normalized to Rn18s  (n=10 biological replicates). Data information: Data were shown as mean ± SEM; *, P < 0.05, two-tailed unpaired Student's t-test.",
    "ncbi_link": "Rn18s: 19791"
  },
  {
    "caption": "(a-d) Degradation of long-lived proteins in MEFs from wild-type (18Q-htt) and mutant huntingtin knock-in (111Q-htt) mice. (a,b) Rates of protein degradation after serum removal (a)",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(a-d) Degradation of long-lived proteins in MEFs from wild-type (18Q-htt) and mutant huntingtin knock-in (111Q-htt) mice. (a,b) Rates of protein degradation after treatment with rapamycin (rapam) or thapsigargin (thapsig) (b).",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(e) Degradation of long-lived proteins in striatal cells from wild-type (7Q-htt) and mutant huntingtin knock-in mice (111Q-htt) in response to different autophagic stimuli.",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(f,g) Rates of protein degradation in wild-type and HD MEFs (f) and striatal cells (g) in the absence (control) or presence (Atg7−) of Atg7 RNA interference.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(a) Top: LC3 immunostaining of 18Q-htt and 111Q-htt MEFs maintained in the presence (+) or absence (-) of serum and inhibitors of lysosomal proteolysis (inhib+). Bottom: mean number of LC3+ vesicles per cell in cells maintained in the presence (left) or absence (right) of serum. n = 4.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(b) Electron micrographs of striatal cells from mutant huntingtin knock-in (111Q-htt) and wild-type (7Q-htt) mice.",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(d) Immunogold for LC3 in striatal cells from mutant huntingtin knock-in mice (111Q-htt), striatal neurons from HD94 mice and lymphoblasts (lymph) from people with HD. Full fields and more details of autophagic vacuoles in Supplementary Figures 10 and 11.",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(a) Electron micrographs of fractions enriched in autophagosomes and autophagolysosomes isolated from liver of 18Q-htt and 111Q-htt mice. Insets: higher magnification of single vesicles. Right: percentage of vesicles with electron-clear (light), vesiculated (multivesicular) or electron-dense (dark) contents. Mean + s.e.m. of three different isolations (> ∼1,000 autophagic vacuoles).",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(a) Immunoblot for the indicated proteins in fractions enriched in APHs and autophagolysosomes (APHL) isolated from livers of 18Q-htt (18Q) and 111Q-htt (111Q) mice. Cyt, cytochrome; Dyn IC, dynein intermediate chain; ADRP, adipose differentiation-related protein; Polyubq, polyubiquitin. Bottom: amount of each protein in 111Q-htt sample, as a multiple of its amount in 18Q-htt sample. Mean + s.d.; n = 4.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(b) Immunoblots for htt and LC3 in homogenates (Homog), cytosol and fractions enriched in APHs and enriched in autophagolysosomes (APHL) isolated from livers of wild-type (18Q-htt) and mutant huntingtin knock-in mice (111Q-htt). Representative one of four experiments with duplicated samples. *P 0.05. Full-length blots in Supplementary Figure 20.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(a) Immunoblot for htt or p62 from total APHs (T) and their corresponding membranes (Mbr) and matrices (Mtx) isolated from livers of wild-type htt (18Q) and 111Q-htt mutant huntingtin knock-in mice (111Q). Left, representative immunoblots. Right, distribution of htt and p62 between Mbr and Mtx calculated by densitometric quantification in six such immunoblots. AV, autophagic vacuoles. Mean + s.d. *P 0.05 compared to wild-type values.",
    "ncbi_link": "htt: 3064
huntingtin: 3064"
  },
  {
    "caption": "(e) Immunoblot for htt and p62 of membranes from autophagic vacuoles shown in d subjected to co-immunoprecipitation for htt under low stringency. Input for 111Q-htt autophagic vacuoles was one-third of that for 18Q-htt to avoid antibody saturation. Levels of htt (top) and p62 (bottom) in the input, immunoprecipitate (IP) and flow through (FT) are shown. Full-length blots in Supplementary Figure 21.",
    "ncbi_link": "htt: 3064
htt: P42858///3064"
  },
  {
    "caption": "(a) Neutral lipids in MEFs from 18Q-htt and 111Q-htt mice stained with BODIPY 493/503.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(b) Electron micrographs of livers from 18Q-htt and 111Q-htt mice. Right: number of lipid droplets (LD) per cell profile (prof.), mean area of LDs and percentage of cellular area occupied by LDs. Mean + s.d.; n = 3.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(c-e) Neutral lipids in striatal cells from 7Q-htt and 111Q-httmice (c), grown on a monolayer of their own astrocytes",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(c-e) Neutral lipids in primary striatal neurons from 18Q-htt and 111Q-httmice grown on a monolayer of their own astrocytes (d)",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(a) Top: immunofluorescence for the mitochondrial marker COX IV in 18Q-htt and 111Q-htt MEFs maintained in the presence or absence of serum. Bottom: number of mitochondria per cell. Mean + s.d. of 10-20 cells in three different experiments.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(d,e) Striatal cells from 7Q-htt and 111Q-htt mice (d) stained with Mitotracker and Mito-ROS. Right, merged images. Percentage of colocalization is indicated at the bottom in d",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "MEFs from 18Q-htt and 111Q-httmice (e) stained with Mitotracker and Mito-ROS. Right, merged images. Percentage of colocalization is indicated at the bottom in d and is displayed in the graph at the bottom in e. CCCP was added to control cells in e as a positive control for depolarization. *P 0.05.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(f,g) Striatal cells from 7Q-htt and 111Q-htt mice untreated or treated with vinblastine were co-stained for LC3 and Mitotracker (f). Arrows, colocalization events. Extended study in Supplementary Figure 16.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(f,g) Striatal cells from 7Q-htt and 111Q-httmice untreated or treated with vinblastine were co-stained for LC3 and BODIPY 493/503 (g). Arrows, colocalization events. Extended study in Supplementary Figure 16.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "G. EZH2-deleted AECs (sgEZH2) reintroducing empty vector (EV), T311 wildtype (WT), a phosphorylated-deficient T311A, or a phosphomimetic T311D form of EZH2 were quantified for the expression of profibrotic genes. Vehicle and TGFβ1 treated  AECs (sgNEG + vehicle / TGFβ1) were used as control. mRNA levels are normalised to HPRT1 expression. (mean + s.d., n = 4 biological replicates, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Kruskal-Wallis/Dunn's).",
    "ncbi_link": "EZH2: 2146
HPRT1: 3251"
  },
  {
    "caption": "E. qPCR  analysis of profibrotic genes in MCs co-culture with AECs shows that depletion of IPO9 in TGFβ1-injured AECs blocks the fibrotic crosstalk with MCs. Data show  mRNA levels of profibrotic genes normalised to S26 (mean + s.d., n = 3 biological replicates with 5 MCs donors, *p < 0.05, ***p < 0.001, ANOVA/Tukey's).",
    "ncbi_link": "IPO9: 55705
S26: 6231"
  },
  {
    "caption": "A. Simple western analysis  (Peggy Sue) and quantifications (right panels) of mouse lung epithelial cells shows increased ph-EZH2 (T311), ph-TAK1, myosin activity (ph-MLC2) and POL2-K7m levels in AAV-mediated TGFβ1  over-expression. Note, increased ph-EZH2 and POL2-K7m levels are attenuated by the EZH2 inhibitor  GSK126, whereas ph-TAK1 and ph-MLC2 levels cannot be rescued by GSK126. Quantifications (right panels) show violin plots, *p < 0.05, **p < 0.01, ***p < 0.001, ns = non-significant, Kruskal-Wallis/Dunn's. Data information: All violin plots display minimum, first quartile, median, third quartile and maximum; n = 5 control, 12  AAV-TGFβ1  and 13 GSK126-treated AAV-TGFβ1 mice.",
    "ncbi_link": "TGFβ1: 21803"
  },
  {
    "caption": "B. Representative of 3D computed tomography (CT) reconstruction of the lung from control, AAV-TGFβ1 and  GSK126-treated AAV-TGFβ1 mice (green: lung tissue, red: airways, and region-of-interest (ROI): blue). Insets show µCT slices in the middle of the  lung from respective mice. Note, GSK126 attenuates TGFβ1-induced lung injury. Quantification (right panel) shows mean  intensity of ROIs from the whole lung (violin plots, *p = 0.0385, **p = 0.0012, ANOVA/Holm-Sidak's). Data information: All violin plots display minimum, first quartile, median, third quartile and maximum; n = 5 control, 12  AAV-TGFβ1 and 13 GSK126-treated AAV-TGFβ1 mice.",
    "ncbi_link": "TGFβ1: 21803"
  },
  {
    "caption": "D. Immunofluorescence analysis of KRT5 as a marker for alveolar metaplastic basal cells and ph-EZH2 (scale bars 100 µm), pro-SFTPC as a marker for alveolar type 2 epithelial cells (scale bars 50 µm) and quantifications (right panels) show percentage of KRT5+ pods area per 10X field and percentage of pro-SFTPC+ cells per 20X field (*p < 0.05, unpaired t-test). Data information: All violin plots display minimum, first quartile, median, third quartile and maximum; n = 5 control, 12 AAV-TGFβ1 and 13 GSK126-treated  AAV-TGFβ1 mice. ",
    "ncbi_link": "TGFβ1: 21803"
  },
  {
    "caption": "(E) Electroporation of mH2A1.2-shRNA results in abnormal cell distribution in the developing neocortex. Electroporation was performed at E13.5, and the mouse  was harvested at E16.5. Scale bar represents 50 μm. (F) Graph shows the percentage of GFP-positive cells distributed in the VZ/SVZ, IZ and CP. n = 7 mice, independent replicates. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.01(**) or P < 0.001(***). n.s., not significant.",
    "ncbi_link": "mH2A1.2: 26914"
  },
  {
    "caption": "(D)Abnormal cell distribution was observed in the mH2A1.2  silenced neocortex. The GFP plasmid was electroporated  into WT and KO  mice brains at E13.5, and the  mice were sacrificed at E16.5. Scale bar represents 50 μm. (E) Graphs of the percentage of GFP-positive cells in the VZ/SVZ, IZ and CP. n = 5 mice, independent replicates. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05(*), P < 0.01(**) or P < 0.001(***). n.s., not significant.",
    "ncbi_link": "GFP: 
mH2A1.2: 26914"
  },
  {
    "caption": "(H) Representative images of E16.5 coronal brain  sections were immunostained for PAX6. The GFP plasmid was electroporated  into WT and KO  mice brains at E13.5, and the  mice were sacrificed at E16.5. Scale bar represents 50 μm. (I) Quantification of  GFP and Pax6 double positive cells in the VZ/SVZ. n=6 mice, independent replicates. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05(*), P < 0.01(**) or P < 0.001(***). n.s., not significant.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(G)Western blot analysis showed that the protein expression levels of neural stem cell marker, including TBR2, PCNA, and PAX6 are increased in mH2A1.2  KO mice compared with WT. (H) Statistics of the normalized density of  TBR2, PCNA, and  PAX6. n=5 mice, independent replicates. Date information: Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05(*). n.s., not significant.",
    "ncbi_link": "mH2A1.2: 26914"
  },
  {
    "caption": "(A) Representative images of  neurons after 4 days of culture in vitro. GFP  expressing plasmid was electroporated into the E13.5  cerebral cortices  of WT and KO  mice  to label neural progenitor cells. After 24 h, the GFP+ cells were isolated and cultured in differentiation medium for 4 days. Scale bar represents 15 μm. (B) Graph shows that the total dendritic length of  neurons  is decreased when  mH2A1.2 is deleted. n = 25 cells from four samples. (C) Statistics show that the number of branch points is reduced upon mH2A1.2 deletion. n = 25 cells from four samples. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05(*), P < 0.01(**).",
    "ncbi_link": "GFP: 
mH2A1.2: 26914"
  },
  {
    "caption": "(I) Representative images of E16.5 cortices  that had been  electroporated  with  GFP or GFP+NKX2.2 into WT and KO  brains  at E13.5. Scale bar represents 50 μm. (J) Graphs of the percentage of  GFP+ cells in the  VZ/SVZ, IZ  and  CP. Overexpression of NKX2-2 restored the distribution of GFP+ cells to the normal state. n=5  mice, independent replicates. Date information: Representative images from at least three independent experiments. Error bars represent the means ± S.E.M.; Two-tailed unpaired t-test, P < 0.05 (*), P < 0.01(**). n.s., not significant.",
    "ncbi_link": "GFP: 
NKX2-2: 18088
NKX2.2: 18088"
  },
  {
    "caption": "C. Western blot for POT1 and DDR markers upon POT1 deletion induced with 0.5 μM 4-OHT. Cl75 - parental cell line. gRNA1 - POT1 knock-out in the population by transient transfection with pSpCas9(BB)-2A-puro containing gRNA1 sequence. EV - corresponding empty vector.",
    "ncbi_link": "Cas9: 57852564
POT1: 25913"
  },
  {
    "caption": "D. Time course of telomere length changes upon POT1 removal in clone 35. d (days) TP0 - time point 0, no 4OHT.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "E. Growth curve for POT1 WT and POT1 knockout cells. Population doublings (PDL) are represented as mean ± SD (three biological replicates).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "F. Quantification for TIFs in EdU positive and EdU negative cells upon POT1 removal in clone 35. The bars show percentage of cells containing more than 5 TIFs ± SD. Experiments were performed in triplicate. At least 120 cells were analyzed per condition per replicate. Significance was determined using two-way ANOVA. p-values are indicated on the graph.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "A. G-overhang assay for clone 35 upon POT1 removal. The bars show relative amounts of single stranded telomeric DNA ± SD. Experiments were performed in triplicate.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "B. 2D gels for telomeric DNA from clone 35 cells with POT1 (NT) and upon POT1 removal for 7 days (7d 4OHT).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "E. Quantification and representative images of anaphases with bridges and micronuclei for non-treated (NT) clone 35 cells and clone 35 treated with 4-OHT for 4 and 7 days. Scale bar equals 6 µm. Experiments were performed in triplicate. The bars show percentage of cells containing anaphases, anaphases with bridges or micronuclei + SD. At least 650 cells were examined per condition per replicate. Significance was determined using one-way ANOVA. p-values are indicated on the graph. In all experiments, POT1 deletion was induced with 0.5 μM 4-OHT.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "A. Western blot for POT1 and DDR markers upon POT1 removal in clone 35 and overexpression of ectopic WT POT1.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "B. Telomere length and G-overhang length analysis for clone 35 upon POT1 removal and overexpression of ectopic WT POT1 (constant-field gel electrophoresis).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "D, E Telomere length and G-overhang length analysis for clone 35 upon POT1 removal and overexpression of ectopic POT1 variants carrying disease-associated mutations (constant-field gel electrophoresis).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "D. Heat map representing changes in levels of selected proteins involved in DNA damage (MRN complex in red, 9-1-1 complex in blue) and HDR proteins (purple) after POT1 knockout induction. Proteins marked with * pass t-test, but not t-test with Benjamini-Hochberg correction (p < 0.05, q < 0.09). Data information: 4-OHT - 4-hydroxytamoxifen, NT - non-treated cells.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "A. Telomere length for clone 35 upon POT1 removal and depletion of selected recombination proteins with siRNA (pulsed-field gel electrophoresis).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "B. Telomere length and G-overhang length analysis for clone 35 upon POT1 removal and inhibition of telomerase with 1 µM GRN163L (pulsed-field gel electrophoresis).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "C. DRIP assay for DNA-RNA hybrid detection at telomeres in clone 35 upon POT1 removal with S9.6 antibody. Dot blots represent two replicates. Bars represent data from three independent experiments ± SD. The IgG signal was subtracted. Significance was determined using one-way ANOVA, p-values are indicated on the graph.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "D. C-circle (CC) assay for clone 35 upon POT1 removal. Bars represent data from three independent experiments ± SD. DNA from ALT positive cell line U2OS was used as positive control. Significance was determined using one-way ANOVA, p-values are indicated on the graph. In all experiments, POT1 deletions was induced with 0.5 μM 4-OHT for 4 and 7 days.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "E. C-overhang length analysis for clone 35 upon POT1 removal (pulsed-field gel electrophoresis, hybridization with Telo-G probe).",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "F. Quantification and representative pictures for visualization of the PML protein (IF, green) and telomeres (FISH, red) in non-treated (NT) clone 35 cells and clone 35 treated with 4-OHT for 4 and 7 days. Arrows indicate co-localizations. Scale bar equals 10 µm. Bars represent data from three independent experiments ± SD. At least 150 cells were examined per condition per replicate. Significance was determined using one-way ANOVA. p-values are indicated on the graph. In all experiments, POT1 deletion was induced with 0.5 μM 4-OHT. Data information: 4-OHT - 4-hydroxytamoxifen, NT - non-treated cells, GRN163L - telomerase inhibitor Imitelstat, siNT -non-tagreting siRNA, negative control.",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "Dynamics of histone modifications after an acclimatizing HS (ACC) or no HS (NHS) in Col-0 wild type at HSP22.0 (A) and HSP70 (B). Seedlings were subjected to ACC or a control treatment (NHS) 4 d after germination. At the indicated time points after the treatments, ChIP-qPCR was performed with antibodies against H3K9ac, H3K4me3, H3K4me2 and H3. Schematics show positions of regions analyzed. Amplicon positions relative to TSS are HSP22.0: 1, -2570 bp; 2, +235 bp. HSP70: 1, 4192 bp downstream of the 3'UTR; 2, +47 bp. Data shown are averages over three biological replicates. Amplification values were normalized to input, H3 and 4 h NHS region 2. The bottom panel shows the H3 signal normalized to input and 4 h NHS region 2. Squares and triangles within bars mark significant differences (p<0.01 and p<0.05, respectively, Student´s t-test) between ACC and NHS samples of the same time point. Error bars indicate SE.",
    "ncbi_link": "HSP22.0: 826616
HSP70: 820438"
  },
  {
    "caption": "A. Transcript levels of the indicated HS-inducible genes after ACC in Col-0 (blue bars) and hsfa2 (orange bars) as determined by quantitative Reverse Transcription-PCR (qRT-PCR). Transcript levels were normalized to TUB6 and the respective NHS harvested at the same time point ([GENE OF INTERESTACC x h/ TUB6ACC x h]/ [GENE OF INTERESTNHS x h/ TUB6NHS x h]). Note that the y-axis is on a log10 scale. Error bars show SE of at least three biological replicates. Asterisks show significant differences between the genotypes at the same time point based on Student´s t-test (*: p<0.05; **: p<0.01).",
    "ncbi_link": "TUB6: 
hsfa2: 817155"
  },
  {
    "caption": "B. Immunoblotting of HSP21 and HSP101 in Col-0 (C) and hsfa2 (h) at the indicated time points after ACC or NHS. TUBULIN was used as a loading control. M, marker.",
    "ncbi_link": "hsfa2: 817155"
  },
  {
    "caption": "H3K4me3 (A) or H3K4me2 (B) levels after an acclimatizing HS (ACC) in Col-0 and hsfa2 at HSP18.2, HSP22.0, HSP70 and APX2 as detected by ChIP-qPCR. Col-0 (blue bars) and hsfa2 (orange bars) seedlings were subjected to ACC or no treatment (NHS) 4 d after germination. At the indicated time points after the treatment, ChIP-qPCR was performed with antibodies against H3K4me3 (A), H3K4me2 (B) and H3 (for normalization). Schematics show positions of regions analyzed (grey bars, UTR; black bar, exons). Intergenic control region 1 is 3123 bp (APX2) or 2570 bp (HSP22.0) upstream of the TSS, or 5311 bp (HSP18.2) or 6725 bp (HSP70) downstream of the TSS, respectively. Data are averages over four biological replicates. Amplification values were normalized to input and H3 and the Col-0 4h NHS region 2 (HSP18.2, HSP22.0 and HSP70) or region 3 (for APX2). *, p<0.05; **, p<0.01 for differences between genotypes at the same time point and treatment; squares and triangles within bars mark significant differences (p<0.01 and p<0.05, respectively) between ACC and NHS samples of the same time point and genotype, Student´s t-test. Error bars indicate SE.",
    "ncbi_link": "APX2: 820121
HSP22.0: 826616
hsfa2: 817155
HSP18.2: 836093
HSP70: 820438"
  },
  {
    "caption": "Figure 4: Histone H3K9ac profiles after ACC in Col-0 and hsfa2 at HSP18.2, HSP22.0, HSP70 and APX2 as detected by ChIP-qPCR.Col-0 (blue bars) and hsfa2 (orange bars) seedlings were subjected to ACC or control treatment (NHS) 4 d after germination. At the indicated time points after the treatments, ChIP-qPCR was performed with antibodies against H3K9ac or H3. Schematics (grey bars, UTR; black bar, exons) show positions of regions analyzed. Intergenic control region 1 is 3123 bp (APX2) or 2570 bp (HSP22.0) upstream of the TSS, or 5311 bp (HSP18.2) or 6725 bp (HSP70) downstream of the TSS, respectively. Data are averages over four biological replicates. Amplification values were normalized to input and H3 and the Col-0 4h NHS region 2 (HSP18.2, HSP22.0and HSP70) or 3 (for APX2). *, p<0.05; **, p<0.01 for differences between genotypes at the same time point and treatment; squares and triangles within bars mark significant differences (p<0.01 and p<0.05, respectively) between ACC and NHS samples of the same time point and genotype, Student´s t-test. Error bars indicate SE.",
    "ncbi_link": "APX2: 820121
HSP22.0: 826616
hsfa2: 817155
HSP18.2: 836093
HSP70: 820438"
  },
  {
    "caption": "Figure 5: HSFA2 associates with HS memory-related genes transiently after an acclimatizing HS.Binding of HSFA2-YFP to the promoter regions of HSP18.2 (A), HSP22.0 (B), APX2 (C), HSP70 (D) and ACTIN7 (E) was determined by ChIP-qPCR. Quantifications represent the enrichment relative to input in %. Red-orange-yellow bars represent time points (0.5 h-4 h-28 h) after a ACC and grey bars represent the respective NHS control samples. Schematics show the promoter region of the respective gene with regions analyzed (arrow, TSS; grey bar, 5'UTR; black bar, exon; black boxes, heat shock elements (5'-nnGnAnnTnCtn-3'). Regions are drawn to scale. Intergenic control region 1 is 4610 bp (HSP18.2) and 4192 bp (HSP70) downstream of the 3'UTR and 2570 bp (HSP22.0) or 3123 bp (APX2) upstream of the TSS, respectively. One representative experiment out of at least four biological replicates is shown. Error bars are SD of three replicates.",
    "ncbi_link": "ACTIN7: 830841
APX2: 820121
HSP22.0: 826616
HSP18.2: 836093
HSP70: 820438"
  },
  {
    "caption": "Figure 6: Expression profiles of HS memory-related genes after a recurring HS show HSFA2-dependent transcriptional memoryResponse of selected HS-inducible loci upon recurring HS as determined by qRT-PCR. Transcript levels of APX2 (A), HSP18.2 (B), HSP22.0 (C), and HSP70 (D) in Col-0 (blue bars) and hsfa2 (orange bars) at the indicated time points after a single HS or two HS separated by 2 d. Plants were subjected to 37°C for 60 min on either d 4, d 6 or on d 4 + d 6 after germination. NHS samples were harvested at the same time points as HS d 4 samples. Transcript levels of four biological replicates normalized to TUB6 are shown. Small brackets compare the two genotypes at the same condition, large brackets compare the same genotype across two treatments (at 1 h after treatment) with Col-0 indicated first (Col-0/ hsfa2). Error bars show SE over four biological replicates. *, p<0.05; **, p<0.01; Student´s t-test.",
    "ncbi_link": "TUB6: 
APX2: 820121
HSP22.0: 826616
hsfa2: 817155
HSP18.2: 836093
HSP70: 820438"
  },
  {
    "caption": "A Model calibration with mCFU-E wild-type cells, and mCFU-E cells overexpressing SHIP1 or PTEN, and BaF3-EpoR wild-type cells. Experimental data represented by filled circles. Error bars represent standard deviation estimated by an error model. Solid lines represent model trajectories.",
    "ncbi_link": "SHIP1: 16331
PTEN: 19211"
  },
  {
    "caption": "B Model prediction of pAKT dynamics in BaF3-EpoR cells overexpressing PTEN or SHIP1. Model predictions are represented by solid lines. Experimental validation data obtained by quantitative immunoblotting represented by filled circles. Error bars represent standard deviation estimated by an error model.",
    "ncbi_link": "SHIP1: 16331
PTEN: 19211"
  },
  {
    "caption": "D Experimental validation of basal DUSP expression in mCFU-E and BaF3-EpoR. Quantitative RT-PCR was performed with all samples on the same plate, allowing a direct comparison of mRNA levels between mCFU-E and BaF3-EpoR cells. Data is normalized to the Rpl32 gene. Ratios of expression in BaF3-EpoR cells compared to mCFU-E cells are shown as box plots. N=10. For details, see Appendix K.",
    "ncbi_link": "Rpl32: "
  },
  {
    "caption": "C Model prediction and experimental validation for RSK, AKT, ERK and S6 activation upon RSK overexpression (oe) and 5 U/ml Epo stimulation in 32DEpoR cells. Simulations are based on measured, cell-type-specific protein abundance of 32D-EpoR cells and global kinetic rates estimated from mCFUE and BaF3-EpoR cells. Model predictions are represented by solid lines. Experimental validation data obtained by quantitative immunoblotting represented by filled circles. Error bars represent standard deviation estimated by an error model. Integrated pS6 was significantly higher upon RSK overexpression as compared to 32D-EpoR wild-type (wt) cells, N=4 (lower right panel). Two-Sample t-Test, *** p<0.005.",
    "ncbi_link": "RSK: 20111"
  },
  {
    "caption": "D Impact of AKT, Ras or PTEN overexpression on BaF3-induced pS6 dynamics in EpoR and BaF3-PTEN cells. Quantitative AKT upon overexpression of PTEN, Ras, a constitutive active BaF3 protein, or the empty vector control in EpoR cells or BaF3-mCFU-E cells. BaF3-factor deprived mCFU-E cells (5x106 cells per condition) and Epo-immunoblotting cells (1x107 cells per condition) were stimulated with 5 U/ml Epo for indicated time points. Cellular lysates were analyzed by S6 employing sequential reprobing anti-pAKT, anti-ppERK, anti-pS6, anti-Epo and to ensure equal loading with anti-beta-actin antibodies. Detection was performed with chemiluminescence using a CCD camera device (ImageQuant). Quantification of pS6 on the right is depicted as fold change to wild-type samples at 30 minutes after Epo stimulation. Error bars represent standard deviation. oe: overexpression. N=3. Welch Modified Two-Sample t-Test, n.s. = not significant, * p < 0.05",
    "ncbi_link": "PTEN: 19211"
  },
  {
    "caption": "C Analysis of cell-cycle indicator genes upon AKT VIII and U0126 treatment. Growth-factor deprived cells were pretreated for half an hour indicated doses of a single inhibitor, followed by stimulation with 5 U/ml Epo for 0 h and 3 h. The expression of cyclinD2, cyclinG2 and p27 was measured by quantitative RT-PCR and normalized to the Rpl32 gene. Genes were selected based on microarray analysis. Experimental data is shown as fold change to unstimulated cells with mean ± standard deviation, N=3. Welch Modified Two-Sample t-Test, n.s. not significant, * p<0.05, ** p<0.01, *** p<0.005.",
    "ncbi_link": "Rpl32: 
cyclinD2: 12444
cyclinG2: 12452
p27: 12576"
  },
  {
    "caption": "Lower panel: Experimental validation of PTEN and SHIP1 overexpression effects on Epo-dependent proliferation. Proliferation was assessed using [3H]-Thymidine incorporation 14 h (mCFU-E) or 38 h (BaF3-EpoR) after retroviral transduction with PTEN or SHIP1 construct for overexpression. Data represented as mean ± standard deviation, N=3. EC50 values are given.",
    "ncbi_link": "SHIP1: 16331
PTEN: 19211"
  },
  {
    "caption": ", Protein fold changes of the CcpA mutant over wild type. Log2 fold changes were calculated from LFQ values p values were calculated based on 2-sided two sample t-tests with a FDR threshold of 0.05 and S­0 equal to 1 (Tusher et al, 2001). Proteins outside the significance lines (FDR = 0.05, S­0 = 1) are significantly changed in expression. Example sets of proteins are highlighted and are labeled with their gene names.",
    "ncbi_link": "CcpA: "
  },
  {
    "caption": " B, C Relative abundance of sgRNAs in cell populations with high versus low signal were visualized as log2 fold chances for basal as well as activated autophagy conditions for (B) p62 or (C) NDP52. Entire data is reported in Dataset EV1 ",
    "ncbi_link": "sgRNAs: "
  },
  {
    "caption": " D-F Validation of TMEM41B. H4 Cas9 cells were infected with sgRNAs targeting TMEM41B or a non-targeting (NT) control, treated with 500 nM AZD8055, 50nM Bafilomycin A1 (BafA1) or DMSO vehicle control for 24 h, and analyzed by immunoblotting. (E, F) p62 and NDP52 band intensities are depicted as total levels relative to vehicle control in H4 Cas9 NT cells (E), or as flux by calculating the ratio in BafA1-treated cells versus vehicle control (F). Data are presented as mean ± SD (n=6 independent experiments) with paired t-test values ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " I HeLa cells were transduced with Cas9 and TMEM41B or NT sgRNAs followed by infection with luciferase-expressing S. typhimurium. Luciferase readings were taken up to 8.5 h post-infection. Results from one representative experiment are presented as mean ± SD (n=8 technical replicates) ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " A H4 Cas9 cells were infected with sgRNAs targeting ATG7, TMEM41B or NT control, treated with 500 nM AZD8055 or vehicle control for 24 h, and analyzed by immunoblotting. B Ratio of LC3-II to LC3-I band intensities are depicted as mean ± SD (n=6 independent experiments) with Wilcoxon test values ",
    "ncbi_link": "ATG7: 10533
TMEM41B: 440026"
  },
  {
    "caption": " C H4 Cas9 TMEM41B and NT control cells were probed by LC3B immunostaining and imaged with an automated CV7000 confocal microscope. Scale bar: 20 μm. D The number of LC3 puncta per cell was quantified using Yokogawa Analysis Software (YAS) and depicted as mean ± SD (n=3 technical replicates) ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " H H4 Cas9 TMEM41B and NT control cells were infected with a RFP-DFCP1 expression construct for 72h, fixed, stained with LC3 antibodies and imaged with an automated CV7000 confocal microscope. Arrowheads point at co-localized LC3 and RFP-DFCP1 puncta. Scale bar: 5 µm. I The number of RFP-DFCP1 puncta positive for LC3 was quantified using ImageJ and depicted as mean ± SD (n=10 technical replicates) ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026
DFCP1: 53349"
  },
  {
    "caption": " J mCherry-GFP-LC3 was expressed in H4 Cas9 TMEM41B KO and NT control cells which were treated with 50nM BafA1 or vehicle control for 24 h, fixed and imaged. Scale bar: 20 μm. The number of mCherry- and GFP-positive puncta per cell was quantified using YAS and are depicted as mean ± SD (n=3 technical replicates) ",
    "ncbi_link": "Cas9: 
LC3: 81631
TMEM41B: 440026"
  },
  {
    "caption": " A H4 Cas9 cells stably expressing NT, TMEM41B or ATG7 sgRNAs were stained with BODIPY 493, NBD cholesterol or BODIPY FL C12 probes for 2 h at 37°C and imaged live with an automated CV7000 confocal microscope. Puncta area per cell was quantified using YAS and depicted as mean ± SD (n=4 technical replicates). Scale bar: 20 μm ",
    "ncbi_link": "ATG7: 10533
TMEM41B: 440026"
  },
  {
    "caption": " B H4 Cas9 TMEM41B KO and NT control cells were treated overnight with 400 μM BSA-conjugated oleic acid or 0.1% BSA as vehicle control, stained for 2 h with HCS LipidTox Green Neutral Lipid Stain and imaged with an automated Operetta microscope. Scale bar: 20 μm ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " D H4 Cas9 TMEM41B KO and NT control cells were probed by ADRP immunostaining and imaged with an automated CV7000 confocal microscope. Scale bar: 20 μm. E Size of ADRP droplets was quantified with YAS and depicted as mean ± SD (n=3 technical replicates) ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " F Protein level of ADRP was probed by immunoblotting in H4 Cas9 TMEM41B KO and NT control cells. G ADRP band intensities were quantified and depicted as mean ± SD (n=4 independent experiments) with paired t-test values ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026"
  },
  {
    "caption": " A H4 Cas9 TMEM41B KO and NT control cells were pulsed with the fatty acid analog Red C12, chased in complete medium or upon serum-deprivation, and stained with MitoTracker. Cells were imaged live with an automated CV7000 confocal microscope. Scale bar: 20 μm ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026"
  },
  {
    "caption": " C-E H4 Cas9 TMEM41B KO and NT control cells were plated in XF96 plates and analyzed using a Seahorse Bioscience XF96. (C) Basal oxygen consumption rates (OCR) and extra cellular acidification rates (ECAR) were measured in cells grown in complete medium. OCR/ECAR ratio is also reported. Data are presented as mean ± SEM (n=30-32 technical replicates) from one representative experiment ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026"
  },
  {
    "caption": " A H4 Cas9 cells stably expressing N-terminally (Myc-TMEM41B) or C-terminally Myc-tagged TMEM41B (TMEM41B-Myc) were probed by calnexin (CANX) and Myc tag immunostaining and imaged with an automated CV7000 confocal microscope. Scale bar: 20 μm ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026"
  },
  {
    "caption": " B-D Endogenous TMEM41B locus was tagged with C-terminal Myc using CRISPR-directed homologous recombination in HeLa cells. HeLa knock-in (KI) cells were compared to parental HeLa (-) and HeLa cells stably transduced with a TMEM41B-Myc over-expression (OE) construct. (B) Confocal micrographs of cells stained with antibodies against CANX and Myc confirming ER localization of both KI and OE TMEM41B-Myc. Scale bar represents 20 μm ",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": "(D) PCR analysis with primers binding to TMEM41B last intron and to Myc tag confirming successful targeting of the endogenous TMEM41B locus with Myc (band labeled with asterisk). M=size marker",
    "ncbi_link": "TMEM41B: 440026"
  },
  {
    "caption": " E H4 Cas9 cells and H4 Cas9 cells stably expressing Myc-TMEM41B or TMEM41B-Myc were lysed and subjected to anti-Myc IP. Eluates were analyzed by mass spectrometry. Enrichment of proteins in IPs from Myc-TMEM41B or TMEM41B-Myc cells versus H4 Cas9 cells is depicted as log2 fold changes. Entire data is reported in Dataset EV2 ",
    "ncbi_link": "Cas9: 
TMEM41B: 440026"
  },
  {
    "caption": "Left graph reports the tumor volume in NSG mice injected with control (shCTR) and antimiR-9 FaDu cells followed for up to 35 days (n=5 mice/group). Data represent the mean (±SD) and unpaired t-test was used to verify the statistical significance at each time point. On the right, typical images of explanted tumors formed by control (shCTR) and antimiR-9 FaDu cells at necropsy.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "qRT-PCR analyses of normalized miR-9 expression, expressed as fold over the untreated condition, in control (shCTR) and antimiR-9 FaDu cells treated with Cetuximab (CTX) for up to four hours. Data represent the mean (±SD) of three independent experiments performed in duplicate and two-way ANOVA test was used to verify the statistical significance.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "Graph reporting the cell viability of control (shCTR) and antimiR-9 FaDu cells treated with increasing concentration of Gefitinib as indicated and evaluated using the MTS assay. Data represent the mean (±SD) of two independent experiments performed in sextuplicate, and unpaired t-test was used to verify the statistical significance per each dose.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "qRT-PCR analyses of Sp1 expression in control (shCTR) and antimiR-9 FaDu cells transiently transduced with PGK-miR-9 or control vector as indicated. Data represent the mean (±SD) of three independent experiments performed in duplicate and two-way ANOVA with Sidak's multiple comparison test was used to verify the statistical significance. qRT-PCR analyses of Sp1 expression in CAL27 cells transfected with pcDNA miR-9 or control vector. Data represent the mean (±SD) of three independent experiments performed in duplicate and unpaired t-test was used to verify the statistical significance.",
    "ncbi_link": "PGK: 
miR-9: 407046
Sp1: 6667"
  },
  {
    "caption": "Graph reporting the normalized Luciferase activity of Sp1 promoter fragments in control (shCTR) or antimiR-9 FaDu cells. Data represent the mean (±SD) of three independent experiments performed in duplicate and unpaired t test was used to verify the statistical significance.",
    "ncbi_link": "miR-9: 407046
Sp1: 6667"
  },
  {
    "caption": "On the left, WB analyses of KLF5 and Sp1 expression in control (shCTR) and antimiR-9 FaDu. Histone H3 expression was used as loading control. On the right, protein quantification analyses of KLF5 and SP1 expression normalized on H3 loading control. Data represent the mean (±SD) of three biological replicates and unpaired t test was used to verify the statistical significance.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "Left, WB analyses of the indicated protein expression in control (shCTR) and antimiR-9 FaDu cells not irradiated (NIR) or treated with 5Gy IR and allowed to repair for the indicated hours (h). Tubulin was used as loading control. On the right, protein quantification analyses of KLF5 and Sp1 expression normalized on tubulin loading control. On the right, graphs report the quantification of the indicated proteins normalized on tubulin expression. Data are expressed as mean (±SD) of three independent experiments and unpaired t test was used to calculate the statistical significance at time point.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "Left panel reports typical immunofluorescence images of control (shCTR) or antimiR-9 FaDu cells, not irradiated (NIR) and analyzed 1, 4 or 8 hours after 2Gy IR (γH2AX green, pS10-H3 red, nuclei in blue). Graphs report the percentage of γH2AX (middle) and pS10-H3 (right) positive cells. Data represent the mean (±SD) of three independent experiments in which at least 10 randomly selected fields were evaluated. Unpaired t test was used to calculate the statistical significance at each time point.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "Kaplan-Mayer curve evaluating the overall survival of HNSCC patients treated with RT+Cetuximab (CTX) combination included in the TCGA dataset, segregated on the expression of miR-9 in the primary tumor (Low expression <75819 reads n=8; High expression ≥75819 reads n=23). Number of evaluated samples (n) and p value are reported in the graph. Statistical significance was calculated with long-rank test.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "Kaplan-Mayer curve evaluating the progression free survival of HNSCC patients treated with RT+Cetuximab (CTX) combination at the CRO-Aviano National Cancer Institute and at the University Cattolica segregated based on miR-9 expression in primary tumors, defined as the expression in above (high expression n=18) or below (low expression n=17) the median expression, as defined by ddPCR. Hazard Ratio (HR) and statistical significance were calculated with long-rank (Mentel-Cox) test and are reported in the graph.",
    "ncbi_link": "miR-9: 407046"
  },
  {
    "caption": "B. Representative images (upper) and QIBC analysis (lower) (solid lines, median; dashed lines, quartiles; >10000 cells analyzed per condition) of Ub(G76V)-GFP  expression in stable U2OS/Ub(G76V)-GFP  cells treated or not with p97i for 4 h. Data information: Data are representative of three independent experiments with similar outcome.",
    "ncbi_link": "GFP: 
Ub: 6233///7311///7314///7316"
  },
  {
    "caption": "D. DOX-treated U2OS/shUb/HA-Ub(WT) and U2OS/shUb/HA-Ub(K27R) cell lines were transfected with shUb-resistant Ub(G76V)-GFP construct and treated or not with  p97i for 4 h. Cell extracts were subjected to GFP IP followed by  immunoblotting  with indicated antibodies. Data information: Data are representative of three independent experiments with similar outcome.",
    "ncbi_link": "GFP: 
HA: 
Ub: 6233///7311
Ub: 6233///7311///7314///7316
Ub: 7311///6233
Ub: 7314///7316///6233///7311"
  },
  {
    "caption": "E. Immunoblot  analysis of DOX-treated U2OS/shUb/HA-Ub cell lines treated or not with MG132 for 4 h. Data information: Data are representative of three independent experiments with similar outcome.",
    "ncbi_link": "HA: 
Ub: 6233///7311///7314///7316
Ub: 7311///6233"
  },
  {
    "caption": "G. DOX-treated U2OS/shUb/HA-Ub(WT) and U2OS/shUb/HA-Ub(K27R) cell lines transfected with indicated Ub(G76V)-GFP expression constructs were subjected to  GFP IP under denaturing conditions followed by immunoblotting  with indicated antibodies. Data information: Data are representative of four (G) independent experiments with similar outcome.",
    "ncbi_link": "GFP: 
HA: 
Ub: 6233///7311///7314///7316
Ub: 7311///6233
Ub: 7316///7314///7311///6233"
  },
  {
    "caption": "A. FLAG IPs from U2OS  cells transfected with indicated FLAG- tagged expression constructs were incubated with purified K27 di-Ub and analyzed by immunoblotting. Data information: Data are representative of three (A independent experiments with similar outcome.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "I. U2OS/Ub(G76V)-GFP and U2OS/Ub(G76V)-20AA-GFP  cell lines were transfected or not with FLAG-UCHL3  C95S expression construct, treated with MG132  for 2 h and subjected to GFP IP  followed by immunoblotting. Data information: Data are representative of three independent experiments with similar outcome.",
    "ncbi_link": "FLAG: 
GFP: 
Ub: 7316///7314///7311///6233
UCHL3: 7347"
  },
  {
    "caption": "A. Schematic diagram of sucrose  density gradient ultracentrifugation for  RNC isolation, and PCR  verification of the 12 screened lncRNA  in both RNC-RNA and total RNA from two groups of  CRC cells, among which the translation level of lnc-AP (marked with a green box) was the most notably dysregulated in both groups of drug-resistant cells (n = 3, biological replicates, mean±SEM, t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance.",
    "ncbi_link": "lnc-AP: 
lncRNA: "
  },
  {
    "caption": "B. PCR analysis of  lnc-AP in serum samples from  oxaliplatin-resistant (PD, n = 15) and -sensitive (PR, n = 9) CRC patients (mean±SEM, t test).",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "C. In the public database lncCAR, high expression level of lnc-AP was correlated with long overall survival in CRC patients.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "E. PCR  and WB analysis of  HEK293T cells transfected with either  lnc-AP-Flag OE plasmid (n = 3, biological replicates, mean±SEM, Dunnett-t test). F. PCR  and WB analysis of HCT116/L-OHP  and SW480/L-OHP cells transfected with either lnc-AP-Flag OE plasmid (n = 3, biological replicates, mean±SEM, Dunnett-t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance. Control referred to the corresponding plasmid vector.",
    "ncbi_link": "Flag: 
lnc-AP: "
  },
  {
    "caption": "J.  IF detection of  pep-AP in HCT116/L-OHP and  SW480/L-OHP cells transfected with either HA-lnc-AP OE plasmid. Scale bar, 10 µm.",
    "ncbi_link": "HA: 
lnc-AP: "
  },
  {
    "caption": "B. CCK-8 assay of inhibition ratio by L-OHP in two groups of  CRC cells with down- or up-regulation of  lnc-AP  (n = 3, biological replicates, mean±SEM). Data information: * si-NC was the abbreviation of commercial normal control of siRNA.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "C.  IF detection of H2AFX for  DNA damage by L-OHP in two groups of CRC cells with down- or up-regulation of   lnc-AP, and nuclei were stained with DAPI (n = 3, biological replicates, mean±SEM, Dunnett-t test).",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "G. Verification of the  interaction between  CEBPA and the upstream region of  AP002387  via ChIP assay followed by  PCR (n = 3, biological replicates, mean±SEM, t test). Data information: * for P < 0.05; ** for P < 0.01",
    "ncbi_link": "AP002387: "
  },
  {
    "caption": "H.  PCR analysis of lnc-AP attenuation and restoration in HCT116  and SW480 cells (n = 3, biological replicates, mean±SEM, Dunnett-t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance. Control referred to the corresponding plasmid vector and si-NC was the abbreviation of commercial normal control of siRNA.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "J. CCK-8 assay of inhibition ratio by L-OHP in  HCT116 and  SW480 cells with  lnc-AP/pep-AP attenuation and restoration (n = 3, biological replicates, mean±SEM). Data information: * si-NC was the abbreviation of commercial normal control of siRNA.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "D. Survival analysis correlated with TALDO1 using TCGA data. Upper: the Kaplan curve of overall survival probability for patients with high or low level of TALDO1. Lower: the  expression graph of TALDO1 in  patients who were dead or not.",
    "ncbi_link": "TALDO1: 6888"
  },
  {
    "caption": "F. MMP detection with down- or up-regulation of   lnc-AP/pep-AP in two groups of  CRC cells. Scale bar, 10 µm.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "C. Flow cytometry of the cell apoptosis ratio under  L-OHP with down- or up-regulation of  lnc-AP/pep-AP in two groups of CRC cells, which was quantified in bar charts on the right (n = 3, biological replicates, mean±SEM, Dunnett-t test). Data information: * for P < 0.05; ** for P < 0.01; NS for no significance. Control referred to the corresponding plasmid vector and si-NC was the abbreviation of commercial normal control of siRNA.",
    "ncbi_link": "lnc-AP: "
  },
  {
    "caption": "Composite immunofluorescent images showing GFP expression of whole-ear sections from DKO*-mT/mG mice at day 5, 7, 15 and 30. Increased GFP expression is shown at day 7 followed by progressive decrease of GFP+ keratinocytes (white dotted line represents basal layer, and red dotted line represents outermost skin layer). n=3 per time point. Quantification analysis of GFP expression (top) and epidermal thickness (bottom) of DKO* mice at different time points during psoriasis-like disease progression. n=6 per time point. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to control group).",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Intravital confocal time-lapse imaging of non-mutant Tomato keratinocytes and mutant GFP keratinocytes of DKO*-mT/mG at day 7 after first tamoxifen injection. Dotted circles emphasize areas in which mutant GFP+ keratinocytes are replaced by non-mutant Tomato+ keratinocytes.",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Percentage of GFP+ area eliminated during intravital confocal time-lapse imaging at day 5, 7 and 15 in DKO*-mT/mG mice (Time-lapse 1:8h). Positive value: Area of GFP increased. Negative value: Area of GFP reduced.",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Fluorescence imaging of DKO*-mT/mG ear skin at day 30 after first tamoxifen injection shows that remaining mutant GFP+ keratinocytes reside along the hair follicles. White dotted line separates epidermis and dermis. White arrows represent GFP+ hair follicles.",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Intravital confocal time-lapse imaging of DKO*-mT/mG at day 15 after first tamoxifen injection. Mutant GFP+ Keratinocytes (white arrows) are maintained around hair follicles.",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Ear pictures of control, DKO*, and DKO*K15 mice after 15 days of induction show clear signs of inflammation and psoriatic-like scales in both models.",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "Representative images of hematoxylin and eosin (H&E) staining of ear sections from control, DKO* and DKO*K15 mice.",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "Ear thickness measurement at different time points during psoriasis-like development in control, DKO* and DKO*K15 mice. n > 5 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to control group).",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "FACS quantification of CD45+ cells from ear skin of control, DKO* and DKO*K15 mice at different time points during psoriasis-like development. n > 5 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to controls).",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "Quantification of IL-17A, IL-6 and LCN2 production in sera of control, DKO* and DKO*K15 mice at day 30 of psoriasis-like disease by ELISA. n > 4 per group. Statistical significance *p<0.05, **p<0.01, ***p<0.001 (t-student two tailed-test relative to controls).",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "Quantification of total number of GFP+ epidermal cells by FACS analysis from DKO*-mT/mG and DKO*K15-mT/mG mice at different time points during psoriasis-like progression compared to Co-mT/mG mice. n = 3-6 per group and time point.",
    "ncbi_link": "mG: 
mT: 
K15: 16665"
  },
  {
    "caption": "Representative immunofluorescence images of ear sections from CoK15-mT/mG and DKO*K15-mT/mG mouse models after 15 days of induction. Red (Tomato), green (GFP) and blue (DAPI). Hyperplasia of Tomato+ keratinocytes in psoriatic-like DKO*K15-mT/mG mouse with clusters of GFP+ keratinocytes are derived from hair follicle K15+ GFP+ stem cells. n=3 per group. Dotted lines separate epidermis and dermis. Quantification analysis of cleaved Caspase-3 (cCas3) and Ki67 in ear skin of DKO*K15-mT/mG mice at different time points during psoriasis-like disease progression.",
    "ncbi_link": "mG: 
mT: 
K15: 16665"
  },
  {
    "caption": "Average number of live primary keratinocytes from co-cultures of GFP+ with Tomato+ bulge HF-SCs at different time points of time lapse capture during 48 hours. Co-culture of HF-SCGFP with HF-SCTom from DKO*-mT/mG mice shows a significant increase of HF-SCTom, while the HF-SCTom from DKO*-mT/mG mice show a normal growth when they are co-culture with HF-SCGFP from control mice. Average number of live primary keratinocytes from co-cultures of GFP+ with Tomato+ basal keratinocytes at different time points of time lapse capture during 48 hours. Co-culture of b-KCGFP with b-KCTom from DKO*-mT/mG mice show significant increase of b-KCTom, while these b-KCTom from DKO*-mT/mG mice show a normal growth when they are co-culture with b-KCGFP from control mice.",
    "ncbi_link": "mG: 
mT: "
  },
  {
    "caption": "Gene expression of TSLP in different epidermal cell subpopulations sorted at mid-term (D7) or late-term (D30) of psoriasis-like progression in DKO* mice.",
    "ncbi_link": "TSLP: 53603"
  },
  {
    "caption": "Quantification of TSLP production in sera of control, DKO* and DKO*K15 mice at day 30 of psoriasis-like disease by ELISA. n = 4 per group.",
    "ncbi_link": "K15: 16665"
  },
  {
    "caption": "TSLP production in conditioned media quantified by ELISA three days after infection with Ad-empty or Ad-cre. n=3 independent experiments.",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "Percentage of EdU+ Tomato+ keratinocytes after blocking with anti-TSLP. Anti-TSLP neutralizes the hyper-proliferation of non-mutantTom KCs in vitro after infection with Ad-cre.",
    "ncbi_link": "cre: 2777477"
  },
  {
    "caption": "Gene expression of Tslpr after TSLP neutralization is reduced. Gene expression of IL-7ra after TSLP neutralization is increased. Gene expression of VEGFα after TSLP neutralization is reduced.",
    "ncbi_link": "Tslpr: 57914
IL-7ra: 16197
VEGFα: 22339"
  },
  {
    "caption": "(A) Dose response curves displaying the percentage of G1-arrested p53-WT (blue) or KO (green) RPE1-FUCCI cells following 24hr incubation with palbociclib (dark solid lines) or 24h after subsequent washout (light dotted lines). Graphs display mean data -/+ SEM from 3 experiments, with at least 500 cells counted per condition per experiment.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) Representative images and quantifications of colony forming assays in p53-WT or KO RPE1 cells treated with palbociclib (1.25μM) for 1, 4 or 7 days and then grown at low density without inhibitor for 10 days. Each bar displays mean data + SEM from 3 experiments.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) Representative immunofluorescence images of p21 levels in p53-WT or KO RPE1 cells, 48 hours after release from 1, 4 or 7 days palbociclib (1.25μM) treatment. Zoom inserts are 3x magnification of the indicated regions. Scale bars = 250 μM. (B) Quantification of p21 intensities in cells treated as in panel A. At least 100 cells were analysed per experiment and graph shows data from 3 experimental repeats. Violin plots display the variation in intensities between individual cells. Horizontal lines display the median, and error bars show 95% confidence intervals. (",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(D-E) Quantification of nuclear morphologies (D) and γH2AX-positive DNA damage foci (E) following palbociclib (1.25μM) treatment in p53 WT and KO RPE1 cells. Cells were treated for 1, 4 or 7 days and then analysed before or after drug washout for 48 hours. 100 cells (nuclear morphology) or 50 cells (γH2AX foci) were scored per condition per experiment, and bar graphs represent mean data +SEM from 6 experiments.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(J-K) Representative immunofluorescence images (J) and quantifications (K) of mitotic DNA replication assays (MiDAS) in p53-KO RPE1 cells released from 7 days of palbociclib (1.25μM) treatment or following 0.4uM aphidicolin treatment for 40Hrs. EdU foci were quantified in nocodazole-arrested cells. Scale bar= 5 μM, zoom inserts = 3x magnification of highlighted areas. 10 cells were analysed per experiment and the bar chart shows the mean + SEM from 3 experimental repeats.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C,D) Quantification of the nuclear morphologies (C) or γH2AX-positive DNA damage foci (D) from MCF7, MCF7 p53 KO or T47D cells that were treated with palbociclib (1μM) for 0, 1, 4, or 7 days and then analysed 48hr after drug washout. Either 100 cells (nuclear morphology) or 50 cells (γH2AX) were scored per condition per experiment and bar graphs represent mean data + SEM from 3 experiments.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) Quantification of colony forming assays of MCF7, MCF7 p53 KO and T47D cells treated with CDK4/6 inhibitor for 0, 1, 4 or 7 days and then grown at a low density without palbociclib for 14-21 days. Bar graphs displays mean data + SEM from 4-5 experiments.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "ERp44KO HeLa cells expressing Ig-λ chains were transfected with wild type (µ), L566A or C575A mutant  µs  chains and Halo-ERp44, or  Halo-ERp44∆RDEL, as indicated. Empty vectors (- or EV) served as controls. A. Aliquots from the spent media (Extracellular) were  blotted  under non-reducing conditions and decorated with anti-µ antibodies. The blue arrow points at the faster migrating µs2L2 released by cells expressing wild type µs  or L566A chains . Expression of  HaloERp44 restores C575-dependent retention, and wild type  µs are secreted only as polymers (black arrow). Traces of covalent HaloERp44-µ2L2 complexes (black asterisks) are detected in the media of cells expressing HaloERp44∆RDEL and  µs  or L566A. The slightly faster mobility  of µs2L2 and µsL complexes released by cells expressing  ERp44∆RDEL suggest that the latter inhibits processing of the N563 glycan, likely hindering it to the Golgi  enzymes upon non-covalent binding. Data information: All membranes were decorated with anti-μ antibodies. Black roundish spots seen in the left panels are artifacts that formed during blotting procedures and signal acquisition.",
    "ncbi_link": "Halo: 
ERp44: 23071"
  },
  {
    "caption": "ERp44KO HeLa cells expressing Ig-λ chains were transfected with wild type (µ), L566A or C575A mutant  µs  chains and Halo-ERp44, or Halo-ERp44∆RDEL, as indicated. Empty vectors (- or EV) served as controls. B. The corresponding cell lysates are shown in this panel. The short black arrow points at the polymers formed in ERp44KO HeLa  cells upon expression of wild type HaloERp44. The black asterisks indicate covalent complexes that this transgene forms with C575 containing µ2L2. Traces of intracellular  µs2L2-ERp44∆RDEL complexes are visible in µs  and L566A but absent from C575A expressing cells. Data information: All membranes were decorated with anti-μ antibodies. Black roundish spots seen in the left panels are artifacts that formed during blotting procedures and signal acquisition.",
    "ncbi_link": "Halo: 
ERp44: 23071"
  },
  {
    "caption": "C. Lysates of the  ERp44KO transfectants were  precipitated with NP-sepharose, resolved under non reducing conditions and the  blot  decorated sequentially with anti-µ, anti-ERp44  or anti-Halo. The two black asterisks point at bands corresponding to covalent complexes containing µs2L2 and endogenous or Halo-tagged ERp44.",
    "ncbi_link": "ERp44: 23071"
  },
  {
    "caption": "C. The experiment shown aims to determine whether ERp44 can bind also to a single C575, or rather to non-native bonds. Aliquots of the lysates from the indicated ERp44KO transfectants were precipitated with NP-Sepharose, resolved under non reducing conditions and the  blot  decorated with anti-λ antibodies or anti-ERp44  as indicated. Black asterisks point to covalent complexes of Halo-ERp44 with µs2L2.",
    "ncbi_link": "ERp44: 23071"
  },
  {
    "caption": "B. Relative mRNA levels for four Foxo3a downstream targets show no significant changes during hibernation.",
    "ncbi_link": "Foxo3a: "
  },
  {
    "caption": "C. Increased levels of phosphorylated Akt (S478) in skeletal muscles of sgk1−/− mice.",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "D. sgk1−/− mice exhibit decreased running distance after 36 days of exposure to a running wheel, (p = 0.01; n = 6 animals per group).",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "E. Isometric force from soleus muscles of WT and sgk1-/- mice during repetitive electrical stimulations for 500 ms. Amplitudes of isometric force from soleus muscles at two stimulation frequencies. Specific force is plotted in all cases. Mean values ± SD from n = 9 (sgk1−/−) and n = 10 (WT) independent animals (p = 0.01).",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "C. Western blots and densitometric analysis of muscle from transgenic and control mice. Downstream targets of the mTOR signalling cascade (p70S6K and 4EBP1) demonstrate significant upregulation of their phosphorylated forms in sgk1tg mice.",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "B. Morphometric analysis demonstrates a decrease in muscle fiber size of the wild−type control mice compared with sgk1tg transgenic littermates (p = 0.0015).",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "C. Western blot and densitometry analysis shows that levels of phosphorylated Foxo3a at S315 and T32 are increased in sgk1tg.",
    "ncbi_link": "sgk1: 20393"
  },
  {
    "caption": "A. Transfection of constitutively active Sgk1 (CA) into immobilized tibialis anterior muscle (green) reveals increased fiber size diameter when compared to control, EGFP only transfected muscle fibers of immobilized tibialis anterior muscles (100 µm). Laminin γ−1 staining (red) outlines the basement membrane and blue staining marks nuclei (DAPI).",
    "ncbi_link": "Sgk1: 20393"
  },
  {
    "caption": "C. Percentage distribution of the minimum Feret's diameter of tibialis anterior muscle immobilized and transfected with eGFP (GFP), wild−type Sgk1 (WT), kinase dead Sgk1 (KD) and constitutively active Sgk1 (CA) compared to non−immobilized control TA muscle (black dotted line).",
    "ncbi_link": "Sgk1: 20393"
  },
  {
    "caption": "Western blot showing siRNA-mediated depletion of FOXA1 and/or FOXA2 in the low-grade CFPAC1 cell line. The three biological replicates used in the subsequent experiments are shown.",
    "ncbi_link": "FOXA1: 3169
FOXA2: 3170"
  },
  {
    "caption": "Heatmap showing row-normalized expression of differentially expressed genes in CFPAC1 cells depleted of FOXA1/2 (FDR ≤ 0.05 and absolute log2 FC ≥ 1). Blue and orange depict down- and up-regulation, respectively.",
    "ncbi_link": "FOXA1: 3169"
  },
  {
    "caption": "Heatmap showing row-normalized expression of differentially expressed genes in PANC1 cells deleted of FOXA2 (FDR ≤ 0.05 and absolute log2 FC ≥ 1). Blue and orange depict down- and up-regulation, respectively.",
    "ncbi_link": "FOXA2: 3170"
  },
  {
    "caption": "Representative Gene Ontology (GO) terms enriched in genes differentially expressed upon FOXA1/2 depletion in CFPAC1 cells. Terms are ranked by the negative log10 p-value from the hypergeometric test. Panels on the right show the effects of FOXA1/2 depletion on cell morphology and adhesion to multiple substrates. Three replicates per condition were used: circularity index was measured on 100 different cells per condition while adhesion is reported as mean of three different fields per replicate for a total of nine observations per condition.",
    "ncbi_link": "FOXA1: 3169"
  },
  {
    "caption": "Representative GO terms enriched in genes differentially expressed upon FOXA2 deletion in PANC1 cells. Terms are ranked by the negative log10 p-value from the hypergeometric test. Panels on the right show the effects of FOXA2 deletion on cell morphology and adhesion to multiple substrates. Three different bulk populations were used as biological replicates: circularity index was measured on 60 different cells per bulk population while adhesion is reported as mean of six different fields per bulk for a total of eighteen observations per condition.",
    "ncbi_link": "FOXA2: 3170"
  },
  {
    "caption": "FOXA2 peaks in CFPAC1 cells were divided into 5 clusters based on their association with HNF1β and the effects of HNF1β loss on FOXA2 binding and chromatin accessibility (determined by ATAC-seq). Clusters 1-4 were HNF1β- positive while cluster 5 was HNF1β-negative. The heat-maps on the left show FOXA2, HNF1β, ATAC-seq and H3K27Ac profiles at FOXA2-bound genomic regions. The three heat-maps on the right show JunB ChIP-seq data and ATAC-seq data in wild type or Jun/JunB double knockout (DKO) CFPAC1 cells. Data are shown in +/- 3 kb regions centered on the summit of FOXA2 peaks.",
    "ncbi_link": "Jun: 3726
JunB: 3726"
  },
  {
    "caption": "Characterization of clusters 1-3. Left: quantification of the indicated signals at FOXA2 bound regions in wild-type (WT) and HNF1β knock-out (KO) cells. Central values represent the median, the bars the 25th and 75th percentile and the vertical lines the lower and upper whiskers. Middle: distribution of FOXA and HNF1β motifs relative to the summit of FOXA2 peaks. Right: over-represented motifs in clusters 1-3 and inferred binding models.",
    "ncbi_link": "HNF1β: 6928"
  },
  {
    "caption": "Quantification of JunB ChIP-seq signals in clusters 1 to 5. (Right) Quantification of ATAC-seq signals in clusters 1 to 5 in wild type and Jun/JunB double KO (DKO) CFPAC1 cells. Central values represent the median, the bars the 25th and 75th percentile and the vertical lines the lower and upper whiskers.",
    "ncbi_link": "Jun: 3726
JunB: 3726"
  },
  {
    "caption": "Representative snapshot showing changes in FOXA2 occupancy, chromatin accessibility and histone acetylation in HNF1β knock-out CFPAC1 cells. The FOXA2 ChIP-seq track in PANC1 cells is also shown for comparison.",
    "ncbi_link": "HNF1β: 6928"
  },
  {
    "caption": "Western blot showing HNF1β over-expression after lentiviral transduction of PANC1 cells. Expression of FOXA2 in wild type and over-expressing (O.E.) cells is shown. Vinculin: loading control.",
    "ncbi_link": "HNF1β: 6928"
  },
  {
    "caption": "Scatter plot showing the genomic distribution of FOXA2 in PANC1 cells transduced with the HNF1β-expressing lentivirus (HNF1B O.E.) and in their matched mock-infected control. The fraction of gained, unchanged and lost FOXA2 peaks overlapping HNF1β ChIP-seq peaks in transduced PANC1 cells is shown in the pie-charts on the right.",
    "ncbi_link": "HNF1B: 6928
HNF1β: 6928"
  },
  {
    "caption": "Representative snapshot from PANC1 cells transduced with the HNF1β-expressing lentivirus. HNF1B O.E.: HNF1B over-expression.",
    "ncbi_link": "HNF1B: 6928
HNF1β: 6928"
  },
  {
    "caption": "FOXA2 ChIP-seq in CFPAC1 cells transduced with a HOXB8-expressing lentivirus and in their matched mock-infected control. Gained (brown) and lost (yellow) FOXA2 peaks are shown. Pie-charts on the right show the fraction of gained, unchanged and lost peaks overlapping HOXB8 ChIP-seq peaks in transduced CFPAC1 cells.",
    "ncbi_link": "HOXB8: 3218"
  },
  {
    "caption": "Expression of HNF1β protein in wild-type and HOXB8-expressing PANC1 cells.",
    "ncbi_link": "HOXB8: 3218"
  },
  {
    "caption": "Representative snapshots from CFPAC1 cells transduced with the HOXB8-expressing lentivirus.",
    "ncbi_link": "HOXB8: 3218"
  },
  {
    "caption": "K GDH-His was inserted into the chromosome of Salmonella to replace GDH-coding gene gdhA named as gdhA::gdhAHis and cultured in minimal media with glucose levels as indicated. The specific activity of GDH from 5 mM glucose was set as a statistical control. Acetylation levels were determined by immunoblotting. The specific activities GDH were measured spectrophotometrically and compared. Immunoblots represent at least two independent experiments K). Each symbol represents an independent biological replicate Data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "His: 
gdhA: 1252817
GDH: 1252817"
  },
  {
    "caption": "GS (C) proteins were expressed from Salmonella wild-type, Δpat and Δpta mutant strains cultured in LB with or without 50 mM glucose.",
    "ncbi_link": "pta: 1253860
pat: 1254174"
  },
  {
    "caption": "F GSWT, GS2KQ and GS2KR were expressed from wild-type, Δpat and ΔcobB Salmonella strains in LB, respectively. The acetylation levels and specific activities of each enzyme were determined. Specific activities of GSWT, GS2KQ and GS2KR expressed from the wild-type strain were set as controls. : Immunoblots represent at least two independent experiments. The degrees of adenylylation GS were determined by spectral analysis of total glutamyltransferase activity. Each symbol represents an independent biological replicate and data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "cobB: 1252739
GS: 1255533
pat: 1254174"
  },
  {
    "caption": "G-H GS and GDH were expressed from the Salmonella strain cultured in LB media supplemented with 100 mM ammonium. GS (G) or GDH (H) were treated with CobB, PatWT and its catalytically inactive mutants PatA810V and PatD592N in vitro. Specific activities of GS and GDH without any treatment were set as controls. Immunoblots represent at least two independent experiments. The degrees of adenylylation GS were determined by spectral analysis of total glutamyltransferase activity. Each symbol represents an independent biological replicate and data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "Pat: 1254174"
  },
  {
    "caption": "B GSs were expressed and purified from Salmonella wild-type and ΔglnE knockout mutants in minimal media with or without 50 mM NAM supplemented with 2 mM glucose and 2 mM ammonium. The specific activity of GS from ΔglnE with NAM treatment was set as the control. Immunoblots represent at least two independent experiments (B). The states of adenylylation GS were determined by spectral analysis of total glutamyltransferase activity (B).",
    "ncbi_link": "glnE: 1254724"
  },
  {
    "caption": "F The specific activities of GSWT, GS2KR and GS2KQ were compared. Each enzyme was expressed in Salmonella wild-type, Δpat and ΔcobB strains cultured in minimal media with 20 mM glucose and either 2 mM or 100 mM ammonium. Specific activities of GS from high ammonium or low ammonium were set as controls. Each symbol represents an independent biological replicate",
    "ncbi_link": "cobB: 1252739
GS: 1255533
pat: 1254174"
  },
  {
    "caption": "A-B Specific activities of endogenous GS in Salmonella wild-type, Δpat, ΔcobB strains (A) and ΔglnA::glnAC, ΔglnA::glnACΔpat, ΔglnA::glnACΔcobB strains (B) were compared before and after glucose shock. : Immunoblots represent at least two independent experiments (A and B). The specific activities of GS before shock were set as controls. Each symbol represents an independent biological replicates and data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "cobB: 1252739
glnA: 1255533
pat: 1254174"
  },
  {
    "caption": "D GSWT, GSY398S and GSY398F were expressed from the Salmonella wild-type, Δpat and ΔcobB strains, respectively. The specific activities of GSWT, GSY398S and GSY398F were compared before and after glucose shock. The specific activities of GS before shock were set as controls. Each symbol represents an independent biological replicates and data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "cobB: 1252739
GS: 1255533
pat: 1254174"
  },
  {
    "caption": "E The cellular activities of GDH were determined in Salmonella ΔgltB, ΔgltBΔpat and ΔgltBΔcobB strains, as well as in the ΔgltBΔpat strain transformed by a pat-containing plasmid and the ΔgltBΔcobB strain transformed by a cobB-containing plasmid before and after glucose shock. The specific activities of GDH before shock were set as controls. Each symbol represents an independent biological replicates and data are from three independent biological replicates and expressed as the mean ± SD",
    "ncbi_link": "cobB: 1252739
gltB: 1254853
pat: 1254174"
  },
  {
    "caption": "A-D Growth curves of ΔgdhA, ΔgdhAΔpat and ΔgdhAΔcobB Salmonella strains were measured in minimal medium with 100 mM ammonium and 50 mM glucose in the absence (A) and presence (B) of 20 mM glutamine in the media. in these strains were also measured at different growth stages.",
    "ncbi_link": "cobB: 1252739
gdhA: 1252817
pat: 1254174"
  },
  {
    "caption": "E Growth curves of Salmonella ΔgdhA strain complemented with GDH (blue), with GDHK128Q (brown), with GDHK128R (red), with GDHK128R supplemented with 50 mM glutamate in culture media (green), with GDHK128R induced with 1 mM IPTG (purple), with GDHDead (orange) and with GDHK128R induced with 1 mM IPTG (black) in the minimal medium with 50 mM glucose and 100 mM ammonium were compared. Growth curves of total protein levels were normalized by Coomassie Brilliant Blue (CBB) staining. Induction and acetylation of GDH was monitored by western blot. Immunoblots represent at least two independent experiments",
    "ncbi_link": "gdhA: 1252817
GDH: 1252817"
  },
  {
    "caption": "G-H Wild-type, ΔcobB and Δpat Salmonella strains were grown under minimal media supplemented with different ratios of glucose and ammonium as indicated. The specific activities of GDH in the cell lysate and steady-state growth rates were determined for each bacterium. Relative GDH activities were normalized to total protein (G) or GDH mRNA (H). Each symbol represents an independent biological replicates",
    "ncbi_link": "cobB: 1252739
GDH: 1252817
pat: 1254174"
  },
  {
    "caption": "A-B Growth curves of Salmonella glnA::glnAWT, glnA::glnAY398S, glnA::glnAY398F, glnA::glnA2KQY398F, glnA::glnA2KQY398S, glnA::glnA2KQY398S-gdhA::gdhAK128Q, and glnA::glnA2KQY398S-gdhA::gdhAK128R strains were measured in minimal medium with 100 mM ammonium and either 5 mM (A) or 50 mM glucose (B) in the media. data are pooled from the three independent experiments",
    "ncbi_link": "gdhA: 1252817
glnA: 1255533"
  },
  {
    "caption": "E-I The bacterial loads of the faeces (E and F), caecum (G), spleen (H), and liver (I) of C57BL/6 mouse littermates infected with Salmonella strains glnA::glnAWT (n=4), glnA::glnAY398S (n=4), glnA::glnA2KQY398S (n=4), glnA::glnA2KQY398SgdhA::gdhAK128Q (n=4), and glnA::glnA2KQY398S-gdhA::gdhAK128R (n=4) were measured by counting colony-forming units (CFU) in cultures of serially diluted homogenates of organs on MacConkey agar plates. Each symbol represents an independent biological replicates (E-I)",
    "ncbi_link": "gdhA: 1252817
glnA: 1255533"
  },
  {
    "caption": "qRT-PCR detection of the fold induction of IFNB1 mRNA relative to unstimulated condition in different cell types. Cells were stimulated with ecGAMP (5 μg/ml) for 4 h.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA abundance in mBMDMs treated with different eCDNs (5 μg/ml) for 4 h.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA in THP-1 cells stimulated with indicated eCDNs (5 μg/ml) for 4 h.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of the fold induction of IFNB1 mRNA relative to unstimulated condition in human CD14+ monocytes derived from PBMC stimulated with indicated eCDNs (5 μg/ml) for 4 h and 8 h. Each symbol represents one individual donor. Data are means+SD averaged from 10 healthy donors.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA abundance in THP-1 cells treated with ecGAMP and icGAMP at indicated concentrations for 4 h.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA abundance in THP-1 cells treated with ec-di-AMP and ic-di-AMP (B) at indicated concentrations for 4 h.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA abundance in mBMDMs treated with ecGAMP and icGAMP (E) at indicated concentrations for 4 h.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA abundance in mBMDMs treated with ec-di-AMP and ic-di-AMP (F) at indicated concentrations for 4 h.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 (B) and IL6 (C) mRNA in THP-1 cells stimulated with ecGAMP (5 μg/ml) or intracellular 2′3′-cGAMP (icGAMP) (0.1 μg/ml) for 4 h in presence of DMSO or dynasore (10 μM). qRT-PCR detection of Ifnb1 (D) and Il6 (E) mRNA in mBMDMs stimulated with ecGAMP (5 μg/ml) or icGAMP (0.1 μg/ml) for 4 h in presence of DMSO or dynasore (10 μM).",
    "ncbi_link": "IFNB1: 3456
Ifnb1: 15977
IL6: 3569
Il6: 16193"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 and IL6 mRNA in THP-1 cells (H, I) and mBMDMs (J, K) stimulated with ecGAMP (5 μg/ml) and icGAMP (0.1 μg/ml), respectively, for 4 h in presence of DMSO or bafilomycin A1 (BafA) (1 μM).",
    "ncbi_link": "IFNB1: 3456
IL6: 3569"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA in scrambled (Scramble) or STING shRNA stably transfected (STING KD) THP-1 cells stimulated with ec-di-AMP (5 μg/ml) and ecGAMP (5 μg/ml) or transfected with ISD or poly(I:C).",
    "ncbi_link": "IFNB1: 3456
STING: 340061"
  },
  {
    "caption": "ELISA detection of IFNβ protein in supernatants of Scramble or STING KD THP-1 cells stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD or poly(I:C).",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA in WT and Sting-/- (Sting KO) mBMDMs stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD.",
    "ncbi_link": "Ifnb1: 15977
Sting: 72512"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA in WT, Sting KO or Sting KO complemented with mouse STING (Sting KO+mSTING) RAW264.7 cells stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD.",
    "ncbi_link": "Ifnb1: 15977
Sting: 72512
STING: 72512"
  },
  {
    "caption": "Western blot detection of indicated proteins in lysates of WT and Sting-/- (KO) mBMDMs stimulated with ecGAMP (5 μg/ml) or transfected with ISD. Data are representative of 3 independent experiments.",
    "ncbi_link": "Sting: 72512"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA levels in STING stable HEK293T cells (HA-STING-HEK293T) stimulated with ecGAMP or icGAMP at 5 μg/ml for indicated times.",
    "ncbi_link": "HA: 
IFNB1: 3456
STING: 340061"
  },
  {
    "caption": "Western blot detection of indicated proteins in HA-STING-HEK293T cells stimulated with increasing amounts of ecGAMP and icGAMP at 5 μg/ml for 24 h. Data are representative of 3 independent experiments.",
    "ncbi_link": "HA: 
STING: 340061"
  },
  {
    "caption": "qRT-PCR detection of the induction of IFNB1 mRNA in HEK293T cells stably transfected with pcDNA3.1-HA (HA), HA-STING and HA-STING+HA-cGAS stimulated with ecGAMP (5 μg/ml), icGAMP (0.1 μg/ml) or transfected with ISD.",
    "ncbi_link": "HA: 
cGAS: 115004
IFNB1: 3456
STING: 340061"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA in WT and CGAS KO THP-1 cells stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD or poly (I:C) for 4 h.",
    "ncbi_link": "CGAS: 115004
IFNB1: 3456"
  },
  {
    "caption": "ELISA detection of IFNβ in supernatants of WT and CGAS KO THP-1 cells stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD or poly(I:C) for 4 h.",
    "ncbi_link": "CGAS: 115004"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA in mBMDMs from WT and Cgas-/- (Cgas KO) mice stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD or poly(I:C) for 4 h.",
    "ncbi_link": "Cgas: 214763
Ifnb1: 15977"
  },
  {
    "caption": "ELISA detection of Ifnb1 in supernatants of mBMDMs from WT and Cgas KO mice stimulated with indicated eCDNs (5 μg/ml) or transfected with ISD or poly(I:C) for 4 h.",
    "ncbi_link": "Cgas: 214763"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA in WT and CGAS KO THP-1 cells stimulated with ecGAMP (5 μg/ml) or icGMAP (0.1 μg/ml) or transfected with ISD.",
    "ncbi_link": "CGAS: 115004
IFNB1: 3456"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA in mBMDMs from WT and Cgas KO stimulated with ecGAMP (5 μg/ml) or icGMAP (0.1 μg/ml) or transfected with ISD.",
    "ncbi_link": "Cgas: 214763
Ifnb1: 15977"
  },
  {
    "caption": "Western blot detection of indicated proteins in lysates of mBMDMs from WT and Cgas KO mice stimulated with ecGAMP (5 μg/ml), icGAMP (0.1 μg/ml) or transfected with ISD. Data are representative of 3 independent experiments.",
    "ncbi_link": "Cgas: 214763"
  },
  {
    "caption": "qRT-PCR detection of IFNB1 mRNA of WT, CGAS KO, CGAS KO complemented with cGAS (CGAS KO+cGAS) or CGAS KO stably transfected with the empty vector (CGAS KO+Vector) THP-1 cells stimulated with ecGAMP (5 μg/ml).",
    "ncbi_link": "CGAS: 115004
cGAS: 115004
IFNB1: 3456"
  },
  {
    "caption": "ELISA detection of IFNβ in supernatants (I) of WT, CGAS KO, CGAS KO complemented with cGAS (CGAS KO+cGAS) or CGAS KO stably transfected with the empty vector (CGAS KO+Vector) THP-1 cells stimulated with ecGAMP (5 μg/ml).",
    "ncbi_link": "CGAS: 115004
cGAS: 115004"
  },
  {
    "caption": "Cellular localization of ecGAMP in WT and CGAS KO THP-1 cells stimulated with FITC-ecGAMP (5 μg/ml, green) for 2 h, nucleus in blue (DAPI). Data are presentative of 5 independent experiments. Scale bar, 10 μm.",
    "ncbi_link": "CGAS: 115004"
  },
  {
    "caption": "Frequency of perinuclear accumulation of FITC-ecGAMP in WT and CGAS KO THP-1 cells stimulated with FITC-ecGAMP (5 μg/ml) for 2 h. Data are means+SD averaged from 5 independent experiments and approximately 100 cells were imaged and counted in each experiment. Each symbol represents the percentage of THP-1 cells with perinuclear cGAMP aggregates in every independent experiment. Mann-Whitney U test was used for statistical analysis. **p<0.01.",
    "ncbi_link": "CGAS: 115004"
  },
  {
    "caption": "qRT-PCR detection of Ifnb1 mRNA (A) of mBMDMs infected with HSV-1 at indicated MOI together with stimulation with ecGAMP at indicated concentrations for 4 h. Data are means+SD averaged from 3 independent experiments performed with technical triplicates. Each symbol represents the mean of technical triplicates. Two-way ANOVA followed by Bonferroni's post hoc test was used for statistical analysis. *, p<0.05; **p<0.01; ***, p<0.001.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "A. Hcp release assay. HA-tagged Hcp (HcpHA) release was assessed by separating cells (C) and cell-free culture supernatant (S) fractions from 109 wild-type (WT), ΔtssM cells or ΔtssM cells carrying the AHT-inducible FLAG-tagged tssM-borne plasmid (tssM+) treated (bulgecin) or not (NT) with bulgecin A prior to tssM gene induction. Proteins were separated by 12.5%-acrylamide SDS-PAGE and the periplasmic TolB protein (control for cell lysis), HcpHA and FLTssM were immunodetected using anti-TolB (middle panel), anti-HA (lower panel) and anti-FLAG (upper panel) antibodies. Molecular weight markers (in kDa) are indicated on the left. The experiment was performed in duplicate and a representative result is shown.",
    "ncbi_link": "tssM: "
  },
  {
    "caption": "A. Hcp release assay. FLAG-tagged Hcp (HcpFL) release was assessed by separating cells (C) and cell-free culture supernatant (S) fractions from 109 WT, ΔmltE cells or ΔmltE cells producing wild-type (mltE+) or E64Q mutant (mltEE64Q) VSV-G-tagged MltE (MltEV) from arabinose-inducible plasmids. Proteins were separated by 12.5%-acrylamide SDS-PAGE and TolB, HcpFL and MltEV were immunodetected using anti-TolB (upper panel), anti-FLAG (middle panel) and anti-VSV-G (lower panel) antibodies, respectively. Molecular weight markers (in kDa) are indicated on the left. The experiment was performed in triplicate and a representative result is shown.",
    "ncbi_link": "mltE: 945655"
  },
  {
    "caption": "C. Co-immunoprecipitation assay. The solubilized lysates from 2×1010 E. coli K-12 W3110 cells co-producing the indicated FLAG-tagged TssMP variants (exported in the periplasm) and VSV-G-tagged MltE protein (Total, T) were subjected to immune precipitation on anti-FLAG-coupled agarose beads. The immunoprecipitated material (IP) was subjected to 12.5%-acrylamide SDS-PAGE and immunodetected with anti-FLAG (upper panel, TssM domains) and anti-VSV-G (lower panel, MltE) antibodies. Molecular weight markers (in kDa) are indicated on the left. The experiment was performed in triplicate and a representative result is shown.",
    "ncbi_link": "TssM: "
  },
  {
    "caption": "A-B. Co-immunoprecipitation assay. The solubilized lysates from 2×1010 EAEC wild-type or ∆mltE cells producing FLAG-tagged TssM (FLTssM) and/or HA-tagged TssJ (TssJHA, panel A) or TssL (TssLHA, panel B) (Total, T) were subjected to immune precipitation on anti-FLAG-coupled agarose beads. The immunoprecipitated material (IP) was subjected to 12.5%-acrylamide SDS-PAGE and immunodetected with anti-FLAG (upper panel, TssM) and anti-HA (lower panel, TssJ or TssL) antibodies. Molecular weight markers (in kDa) are indicated on the left. The experiments were performed in triplicate and a representative result is shown.",
    "ncbi_link": "mltE: 945655"
  },
  {
    "caption": "C. BS3 cross-linking assay. 2×109 cells of the indicated strain producing FLAG-tagged TssM (with the exception of ∆tssM cells) were treated (+) or not (-) with the BS3 cross-linker agent. After the cross-linking reaction, cells were boiled in Laemmli buffer and total proteins were subjected to 7%-acrylamide SDS-PAGE and immunodetected with anti-FLAG antibodies. The TssM protein (FLTssM) and its complexes (*, TssM-TssJ; **, TssM-TssL) are indicated on the right as well as the TssM dimer (arrow). Molecular weight markers (in kDa) are indicated on the left. The experiment was performed in triplicate and a representative result is shown.",
    "ncbi_link": "tssM: "
  },
  {
    "caption": "D. Fluorescence microscopy. Recordings showing TssM localization using the chromosomally-encoded sfGFP-tssM fusion in wild-type (WT) or ΔmltE cells or ΔmltE cells producing the wild-type (mltE+) or catalytic variant (mltEE64Q) MltE protein. Scale bars are 1 μm. The experiment was performed in triplicate and a representative result is shown.",
    "ncbi_link": "MltE: 945655
mltE: 945655"
  },
  {
    "caption": " A Deletion of siaA, siaB, siaC, or siaD regulates biofilm formation. The biofilm formation of the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down) ",
    "ncbi_link": "siaD: 879346
siaC: 878493
siaB: 882156
siaA: 879545"
  },
  {
    "caption": " B The intracellular levels of c-di-GMPin PAO1, ΔsiaC, ΔsiaB and the corresponding complemented strains were detected by LC-MS/MS ",
    "ncbi_link": "siaC: 878493
siaB: 882156"
  },
  {
    "caption": " C SiaB and SiaC regulated biofilm formation is dependent on SiaD. Biofilm formation by the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down)",
    "ncbi_link": "SiaD: 879346
SiaC: 878493
SiaB: 882156"
  },
  {
    "caption": " D SiaC is required for the function of SiaD. Biofilm formation by the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down)",
    "ncbi_link": "SiaD: 879346
SiaC: 878493"
  },
  {
    "caption": " E Bacterial two-hybrid assay reveals an interaction between SiaC and SiaD. The recombinant strains harboring different vectors were separately streaked on nonselective and dual-selective media (3-amino-1, 2, 4- triazole + streptomycin). NA represents the empty vector pBT or pTRG. The strain expressing LGF2 and Gal11P was used as positive controls ",
    "ncbi_link": "LGF2: 
Gal11: 854106"
  },
  {
    "caption": " F Pull down assays confirmed the interaction between SiaC and SiaD. Cell lysates of P. aeruginosa containing pMM67EH-siaD-Flag were incubated with GST or GST-SiaC individually, and protein complexes were captured by glutathione beads ",
    "ncbi_link": "Flag: 
GST: 
siaD: 879346
SiaC: 878493"
  },
  {
    "caption": " A Bacterial two-hybrid assay reveals an interaction between SiaB and SiaC. The recombinant strains harboring different proteins were separately streaked on nonselective and dual-selective media (3-amino-1, 2, 4- triazole + streptomycin). NA represents the empty vector pBT or pTRG. The strain expressing LGF2 and Gal11P were used as positive controls. ",
    "ncbi_link": "LGF2: 
Gal11: 854106"
  },
  {
    "caption": " B Pull-down assays confirmed the interaction between SiaB and SiaC. Cell lysates of P. aeruginosa containing pMM67EH-siaC-Flag were incubated with GST or GST-SiaB individually, and protein complexes were captured by glutathione beads. ",
    "ncbi_link": "Flag: 
GST: 
siaC: 878493
SiaB: 882156"
  },
  {
    "caption": " D SiaB-mediated regulation of biofilm formation is dependent on SiaC. The biofilm formation of the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). ",
    "ncbi_link": "SiaC: 878493
SiaB: 882156"
  },
  {
    "caption": " E Bacterial two-hybrid assayreveals an interaction between SiaC and SiaA PP2C-like domain. NA represents the empty vector pBT or pTRG. The recombinant strains harboring different proteins were separately streaked on nonselective and dual-selective media (3-amino-1, 2, 4- triazole + streptomycin). The strain expressing LGF2 and Gal11P were used as positive controls. ",
    "ncbi_link": "LGF2: 
Gal11: 854106"
  },
  {
    "caption": " F Pull-down assays confirmed the interaction between SiaC and SiaA. Cell lysates of P. aeruginosa containing pMM67EH-siaA-Flag were incubated with GST or GST-SiaC individually, and protein complexes were captured by glutathione beads. ",
    "ncbi_link": "Flag: 
GST: 
SiaC: 878493
siaA: 879545"
  },
  {
    "caption": " G Pull-down assays confirmed the interaction between SiaC and SiaA PP2C-like domain. Cell lysates of P. aeruginosa containing pMMB67EH-siaA386-Flag were incubated with GST or GST-SiaC individually, and protein complexes were captured by glutathione beads. ",
    "ncbi_link": "Flag: 
GST: 
SiaC: 878493
siaA: 879545"
  },
  {
    "caption": " E Over-expression of SiaCT68A restored the ability of ΔsiaA to form biofilm. The biofilm formation of the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). F Deletion of ΔsiaB in the ΔsiaA background strain restored the ability of ΔsiaA to form biofilm. The biofilm formation of the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). ",
    "ncbi_link": "SiaC: 878493
siaB: 882156
siaA: 879545"
  },
  {
    "caption": " G Production of c-di-GMP at the indicated time-point by SiaD with SiaC or SiaCT68A was determined by HPLC. To evaluate the effect of SiaB-mediated phosphorylation on SiaD DGC activity, SiaC or SiaCT68A was pretreated by SiaB in the presence of 1 mM ATP before reaction initiation. ",
    "ncbi_link": "SiaD: 879346
SiaC: 878493
SiaB: 882156"
  },
  {
    "caption": " C SiaCE33A partially restored the biofilm formation of ΔsiaA. The biofilm formation by the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). ",
    "ncbi_link": "SiaC: 878493
siaA: 879545"
  },
  {
    "caption": " D Triple mutation of E61A-Q64A-R67A is important for the function of SiaB. The biofilm formation by the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). ",
    "ncbi_link": "SiaB: 882156"
  },
  {
    "caption": " E Leu110 and Phe174 residues are important for SiaB function. The biofilm formation by the indicated strains was displayed with crystal violet staining (up) and quantified with optical density measurement (down). Data represent the means and SDs of three biological replicates. **, P<0.01 based on one-way ANOVA test. ",
    "ncbi_link": "SiaB: 882156"
  },
  {
    "caption": "(G) Representative electron microscopy of mitochondria and (H) quantification of the percentage of ER-mitochondria contact sites (ER-mito contact) per mitochondria of HeLa cells expressing EGFP-ORP5, EGFP-ORP8 together with HRP-KDEL, to visualize the ER. Control (Ctrl) consisted of HeLa cells overexpressing only HRP-KDEL.",
    "ncbi_link": "ORP5: 114879
ORP8: 114882"
  },
  {
    "caption": "(E) Representative EM images of ER-mitochondria contacts in the indicated overexpression conditions. (F) Quantification of the percentage of ER-mitochondria contact sites (ER-mito contact) per mitochondria of HeLa cells transfected with HRP-KDEL (Ctrl) or co-transfected with PTPIP51-HA and EGFP or PTPIP51-HA and EGFP-ORP5 or PTPIP51-HA and EGFP-ORP8 (n=30 cells and 1082-1223 mitochondria). % ER-mitochondria contact sites ±SEM. Data are representative of three independent replicates. **P<0,001, *P<0,05.",
    "ncbi_link": "PTPIP51: 55177"
  },
  {
    "caption": "(G) EGFP, EGFP-ORP5 or EGFP-ORP8 were immuno-precipitated from lysates of HeLa cells co-expressing PTPIP51-HA and treated with control (siCtrl) or VAPA and VAPB (SiVAPA/B) siRNAs and analyzed by western blot using antibodies against GFP (ORPs), HA (PTPIP51), VAPA, VAPB and tubulin.",
    "ncbi_link": "VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "(A) Confocal images of HeLa cells transfected with EGFP-ORP5, EGFP-ORP5PH or EGFP-ORP5ORD and immunostained using anti-TOM20 antibody to visualize mitochondria. Scale bar, 10 μm.",
    "ncbi_link": "ORP5: 114879"
  },
  {
    "caption": "(C-D) Confocal images of HeLa cells transfected with EGFP-ORP5PH or EGFP-ORP5ORD (C) together with PTPIP51-HA and immunostained using HA antibody to detect PTPIP51. Scale bar, 10 μm.",
    "ncbi_link": "ORP5: 114879"
  },
  {
    "caption": "(C-D) Confocal images of HeLa cells transfected with EGFP-ORP5, EGFP-ORP5L389D or EGFP-ORP8L425D (D) together with PTPIP51-HA and immunostained using HA antibody to detect PTPIP51. Scale bar, 10 μm.",
    "ncbi_link": "ORP5: 114879"
  },
  {
    "caption": "(E) EGFP-ORP5, EGFP-ORP8, EGFP-ORP5L389D, EGFP-ORP8L425D, GFP-Sec61β or EGFP alone were immunoprecipitated from lysates of HeLa cells co-expressing PTPIP51-HA and analyzed by western blot with antibodies against GFP and HA.",
    "ncbi_link": "ORP5: 114879
ORP8: 114882"
  },
  {
    "caption": "(A) ORP5, ORP8 and actin levels of HRP-KDEL-expressing HeLa cells treated with Ctrl siRNAs (siCtrl) or siRNAs against ORP5 (siORP5) or ORP8 (siORP8).",
    "ncbi_link": "ORP5: 114879
ORP8: 114882"
  },
  {
    "caption": "(B) Electron microscopy of HRP-KDEL-expressing HeLa cells treated with Ctrl siRNAs or siRNAs against ORP5 or ORP8. Red arrows indicate ER-PM contact sites. Scale bar, 2 μm. Insets show representative mitochondria and red arrows in the insets indicate ER-mitochondria contacts. Inset scale bar, 500nm.",
    "ncbi_link": "ORP5: 114879
ORP8: 114882"
  },
  {
    "caption": "(C) Representative EM micrographs showing the morphology of mitochondria in siCtrl, siORP5 and siORP8-treated cells. Scale bar, 1 μm. (D) Quantifications of the number of mitochondria with altered morphology in the indicated siRNA conditions. % altered mitochondria ±SEM, n=25 cells and 632-710 mitochondria. *P<0,001 compared to siCtrl.",
    "ncbi_link": "ORP5: 114879
ORP8: 114882"
  },
  {
    "caption": "(E) Mitochondrial oxygen consumption rate (OCR) measured in Ctrl and ORP5 siRNA transfected cells. OCR trace was obtained by sequential measurement of basal OCR (OCRBAS), OCR after the addition of oligomycin (OM) and OCR after addition of antimycin A (AA). Note the reduced basal OCR (OCRBAS) compared to ctrl siRNA cells. Error bars denote ±SEM. Data are the mean of 4 independent repeats (n=4), *P<0,05.",
    "ncbi_link": "ORP5: 114879"
  },
  {
    "caption": "C. Quantification of Cre activity by dual luciferase assays (mean±SD, n=3). Data information Npu: Nostoc punctiforme, Ssp: Synechocystis sp., CDS: coding sequence.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "D. Quantification of tTA activity by dual luciferase assays (mean±SD, n=3 (N and C) or n=7 (N/C)). Data information: Npu: Nostoc punctiforme CDS: coding sequence.",
    "ncbi_link": "tTA: "
  },
  {
    "caption": "A-B. Scheme of engineered Spc and Ccsp loci after integration of split-Cre and split-tTA effectors (red mark = stop codon) and comparison of endogenous SPC or CCSP expression and YFP or mCherry reporter expression in lung sections. Blue: DAPI. Scale bar: 100 µm.",
    "ncbi_link": "tTA: 
Cre: 2777477
Ccsp: 22287
Spc: 20389"
  },
  {
    "caption": "C-D. β-galactosidase and H&E staining of lung sections from BASC tracer and BASC viewer animals. Scale bars: 500 µm (overview) and 20 µm (boxed magnification).",
    "ncbi_link": "β-galactosidase: 12091"
  },
  {
    "caption": "A. Sequential microscopic imaging of epifluorescence and β-galactosidase activity in lung sections of adult BASC viewer animals. Arrow highlights labeled BASC at BADJ (magnified in box). Blue: DAPI. Scale bars: 100 µm (overview) and 20 µm (boxed magnification).",
    "ncbi_link": "β-galactosidase: 12091"
  },
  {
    "caption": "B. Sequential microscopic imaging of epifluorescence and β-galactosidase activity in lung sections of control and injured BASC v-race mice. Clusters of BASC-derived AT2 (YFP+) and Club cells (mCherry+) are highlighted. Blue: DAPI. Scale bar: 200 µm.",
    "ncbi_link": "β-galactosidase: 12091"
  },
  {
    "caption": "E. Cyclin D1  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following siRNA-mediated knockdown of  cyclin D in control and etoposide-treated cells. Boxplots show data from four independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "ncbi_link": "cyclin D: 896///894///595"
  },
  {
    "caption": "F. Cyclin D1  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following doxycycline  (dox)-induced upregulation of  cyclin D1 in control and etoposide-treated cells. Boxplots show data from six independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "ncbi_link": "cyclin D1: 595"
  },
  {
    "caption": "G. Cyclin A  abundance (left) and the proportion of polyploid  cells (right), as measured by immunofluorescence  and Hoechst staining, respectively, following doxycycline  (dox)-induced upregulation of cyclin A2  in control and etoposide-treated cells. Boxplots show data from six independent replicates (gray circles). Data information: Statistical significance in right panels was determined using a two-way analysis of variance (ANOVA) with Sidak's post hoc test (*** p < 0.001, * p = 0.02). boxes show the interquartile range, the whiskers indicate the full distribution of points and the central band represents the population.",
    "ncbi_link": "cyclin A2: 890"
  },
  {
    "caption": "D Changes (Δ g) in inguinal WAT (iWAT) mass of mice in (C). n=5. *P<0.05, **P<0.01 relative to GFP by Student's t-test. N.S., not significant. E Changes (Δ g) in epididymal WAT (eWAT) mass of mice in (C). n=5. *P<0.05, **P<0.01, ***P<0.001 relative to GFP by Student's t-test. N.S., not significant. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "F Expression of Pltp mRNA in indicated tissues. Data are shown by relative Pltp mRNA levels normalized by 18s expression. n=3 for all tissues (except BAT and WAT n=5, Testis n=2). *P<0.05 Pltp expression in BAT vs other tissues (except testis and lung) by Student's t-test.",
    "ncbi_link": "18s: 
Pltp: 18830"
  },
  {
    "caption": "G Plasma PLTP activity from control (Ppargflox/flox) and BAT-less mice (Pparg UCP1-KO, Ucp1-Cre x Ppargflox/flox). Following 6-h fasting plasma was obtained from PpargUCP1-KO mice and littermate control. n=3 for both groups. *P < 0.05 relative to control mice by Student's t-test.",
    "ncbi_link": "Cre: 2777477
Pparg: 19016
Ucp1: 22227
UCP1: 22227"
  },
  {
    "caption": "H PLTP protein levels in the culture conditioned medium from primary differentiated inguinal adipocytes of wild type (WT) and aP2-PRDM16 mice [24]. Peptide levels was determined by quantitative proteomics. n=2 for both groups.",
    "ncbi_link": "PRDM16: 70673"
  },
  {
    "caption": "I Transcriptional regulation of the Pltp gene by PRDM16 and PPARγ. ChIP-seq data for PRDM16 and PPARγ were obtained from [31,32], respectively.",
    "ncbi_link": "Pltp: 18830"
  },
  {
    "caption": "B Changes in body weight of mice in (A) during 10 weeks of HFD. n=9 for GFP and n=8 for PLTP (cohort 1). *P<0.05, **P<0.01, ***P<0.01 relative to GFP by two-way ANOVA repeated measures followed by Bonferroni's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "C Changes in food intake of mice in (A) during 10 weeks of HFD (cohort 1). n=9 for GFP (cage 1 = 5 mice; cage 2 = 4 mice) and n=8 for PLTP (cage 1 = 4 mice; cage 2 = 4 mice)",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "D Body composition of mice in (A) at 10 weeks of HFD determined by EchoMRI. n=9 for GFP and n=8 for PLTP (cohort 1). *P<0.05 relative to GFP by two-way ANOVA followed by Tukey's test. N.S., not significant.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "E Whole-body energy expenditure of mice at 3 weeks of HFD. Area under the curve (AUC) of VO2 is shown in the right graph. n=7 for GFP and n=8 for PLTP (cohort 2). *P<0.05 relative to GFP by Student's t-test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "F Physical movement of mice at 3 weeks of HFD as determined by metabolic cage analysis. n=7 for GFP and n=8 for PLTP (cohort 2). N.S., not significant by Student's t-test",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "G OCR in the interscapular BAT and iWAT of control and PLTP-treated mice. One week after the treatment, BAT and iWAT were isolated from mice (7 weeks old) that received adenovirus for GFP or PLTP. n=5 for both groups. *P<0.05 relative to GFP by Student's t-test. N.S., not significant.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "H Gene expression of indicated thermogenic genes in (A) from interscapular BAT for GFP (n=8) and PLTP (n=8) groups (cohort 1) except n=7 for Ucp1 of the PLTP group. Tbp was used as an internal control. *P<0.05, **P<0.01 relative to GFP by Student's t-test. N.S., not significant.",
    "ncbi_link": "Tbp: 
GFP: 
PLTP: 18830
Ucp1: 22227"
  },
  {
    "caption": "A Glucose tolerance test of mice that received AAV control (GFP) or PLTP at 10 weeks of HFD. After eight hours of fasting, 2 g/kg body weight of glucose was administered. n=9 for GFP and n=7 for PLTP. *P<0.05, **P<0.01 relative to GFP by two-way ANOVA repeated measures followed by Bonferroni's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "B Insulin tolerance test of mice in (A) at 10 weeks of HFD. Mice were fasted for four hours and administered insulin (0.75 U/kg body weight). n=9 for GFP control and n=7 for PLTP. *P<0.05, **P<0.01 relative to GFP by two-way ANOVA repeated measures followed by Bonferroni's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "C Fasting insulin levels of mice in (A) at 10 weeks of HFD. Blood samples were harvested after eight hours of fasting. n=5 for GFP and n=4 for PLTP. *P<0.05 relative to GFP by Student's t-test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "D Glucose tolerance test of mice that received AAV control (GFP) or PLTP at 6 weeks of HFD. Note that no difference was found in body weight between the groups by two-way ANOVA repeated measures followed by Bonferroni's test.. After eight hours of fasting, 2 g/kg body weight of glucose was administered. n=7 for GFP control and n=10 for PLTP. AUC of glucose is shown in the right graph. *P<0.05 by Student's t-test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "E 18F-FDG PET/CT scan images of mice that received adenovirus GFP (control) or PLTP at 14 weeks of HFD. Mice received CL316,243 at dose of 1 mg/kg of body weight 30 min before the PET/CT images. Representative images of n=5 for both groups. Yellow arrows indicate anatomical references as bladder, heart and interscapular BAT.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "F Quantification of 18F-FDG uptake in indicated tissues from mice in (E). After the 18F-FDG PET/CT imaging, indicated tissues were harvested and the radioactivity was measured by scintillation counter. n=5 for both groups. *P<0.05 relative to GFP by Student's t-test. N.S., not significant.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A Lipidomics-based quantification of indicated lipid species in mice that received tail-vein injection of adenovirus expressing PLTP or GFP (control). Blood and tissues were harvested after 10 weeks of HFD. n=4 for GFP and n=5 for PLTP in mice on HFD. LPC = (lyso)phosphatidylcholine, LPE = (lyso)phosphatidylethalonamine, PA = phosphatidic acid, SM = sphingomyelin, TAG = triglycerides, FFA = free fatty acid. Statistical analysis is demonstrated (P value) relative to GFP by Student's t-test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "B Plasma total cholesterol levels in mice that received adenovirus GFP (control) or PLTP. Blood and tissues were harvested seven days after adenovirus infection. n=8 in mice on RD and n=7 in mice on HFD for 14 weeks. ***P<0.001 relative to GFP by Student's t-test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "C Relative mRNA levels of indicated genes in the liver of mice on HFD. Tbp was used as an internal control. n=4 for GFP and n=6 for PLTP. *P<0.05, **P<0.01 relative to GFP by Student's t-test.",
    "ncbi_link": "Tbp: 
GFP: 
PLTP: 18830"
  },
  {
    "caption": "D Bile acid levels in the liver of mice in (B). n=8 in mice on RD and n=6 in mice on HFD. *P<0.05, **P<0.01 relative to GFP by Student's t-test.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "E Bile acid levels in the plasma of mice in (B). n=8 in mice on RD and n=7 in mice on HFD. ***P<0.001 relative to GFP by Student's t-test. F Bile acid levels in the feces of mice in (B). Feces were collected from mice on RD and HFD after seven days of treatment. n=7 in mice on RD and HFD. **P<0.01, ***P<0.001 relative to GFP by Student's t-test. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "H Relative expression of Ucp1 in differentiated brown adipocytes treated with cholic acid (CA). Cells were treated with CA at indicated concentrations for 24 h. 0.1% ETOH was used as vehicle control (Ctr). n=3. Ucp1 mRNA expression was normalized by Tbp as an internal control. **P<0.01 relative to Ctr by one-way ANOVA followed by Tukey's test. N.S., not significant.",
    "ncbi_link": "Tbp: 
Ucp1: 22227"
  },
  {
    "caption": "B Relative expression of Pltp in liver of mice that received adenovirus GFP (control) or PLTP. n=4 for GFP, n=6 for PLTP and n=6 for PLTPM159E. **P<0.01 relative to GFP by ANOVA one-way followed by Tukey's test. N.S., not significant.",
    "ncbi_link": "GFP: 
Pltp: 18830
PLTP: 18830"
  },
  {
    "caption": "C Plasma PLTP concentration in mice that received adenovirus GFP or PLTP as determined by quantitative mass spectrometry. n=4 for GFP, n=6 for PLTP and n=6 for PLTPM159E. ***P<0.001 relative to GFP by ANOVA one-way followed by Tukey's test. N.S., not significant.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "D Plasma PLTP activity in mice that received adenovirus GFP or PLTP. n=4 for GFP, n=6 for PLTP and n=6 for PLTPM159E. ***P<0.001 PLTP relative to GFP and PLTPM159E; *P<0.05 PLTPM159E relative to GFP by ANOVA one-way followed by Tukey's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "E Changes in body weight of mice that received AAV control or PLTP during 10 weeks of HFD. n=8 for GFP, n=10 for PLTP and n=10 for PLTPM159E. *P<0.05, **P<0.01 relative to PLTPM159E by two-way ANOVA repeated measures followed by Bonferroni's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "F Relative Ucp1 expression in BAT of mice that received AAV GFP (control) or PLTP at 10 weeks of HFD. n=4 for GFP, n=5 for PLTP and n=4 for PLTPM159E. Tbp was used as an internal control. *P<0.05, **P<0.01 by ANOVA one-way followed by Tukey's test.",
    "ncbi_link": "Tbp: 
GFP: 
PLTP: 18830
Ucp1: 22227"
  },
  {
    "caption": "G Glucose tolerance test of mice that received AAV GFP or PLTP at 10 weeks of HFD. n=5 for GFP and n=6 for both PLTP and PLTPM159E. *P<0.05, **P<0.01, ***P<0.001 PLTP relative to GFP by two-way ANOVA repeated measures followed by Bonferroni's test. AUC of glucose, shown in the right graph, was analyzed by one-way ANOVA followed by Tukey's test. N.S., not significant.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "H Plasma total cholesterol of mice that received AAV control or PLTP at 10 weeks of HFD. n=7 for all groups. *P=0.05 by ANOVA one-way followed by Fisher's LSD test. N.S., not significant.",
    "ncbi_link": "PLTP: 18830"
  },
  {
    "caption": "I Plasma bile acids in (H). n=7 for all groups. ***P<0.001 PLTP relative to GFP and PLTPM159E by ANOVA one-way followed by Tukey's test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "J Plasma phospholipid in (H). n=7 for all groups. ***P<0.001 PLTP and PLTPM159E relative to GFP; *P<0.05 PLTP relative to PLTPM159E by ANOVA one-way followed by Fisher's LSD test.",
    "ncbi_link": "GFP: 
PLTP: 18830"
  },
  {
    "caption": "Microtubule organization in wild type stamen filament cells. (D-F) Microtubule organization in the stamen filament cells of lue1 and ktn80.1234. Arrows indicate microtubule crossovers. Dotted lines indicate abnormal microtubules.",
    "ncbi_link": "ktn80.1: 837657
lue1: 844375"
  },
  {
    "caption": "Time-lapse images showing that KTN1 is associated with microtubule severing at crossover sites in wild type filament cells. GFP-labeled KTN1 fluorescent particles are pseudo-colored in red, and microtubules (labeled with mCherry-TUB6) are shown in green. Yellow arrows indicate KTN1 at microtubule crossover sites. Asterisks indicate the location at which a microtubule has been severed at a crossover site. Time-lapse images showing that KTN1 cannot be recruited to crossover sites and no severing was observed in ktn80.1234 filament cells. Yellow open arrows indicate microtubule crossovers, which remain stable for a long time.",
    "ncbi_link": "ktn80.1: 837657"
  },
  {
    "caption": "Comparison of the morphologies of the stamen filament cells in wild type and qui-2.",
    "ncbi_link": "qui-2: 844206///827623///824239///843845///838518"
  },
  {
    "caption": "EMSA showing that BZR1 binds to the E-box of the KTN80.4 promoter regions in vitro. Nonlabelled (free) native probe in 10- to 100-fold molar excess relative to the biotin-labeled native probe was used as a cold competitor. The mutant probe was used as a negative control.",
    "ncbi_link": "KTN80.4: "
  },
  {
    "caption": "Time-lapse images showing that KTN1 is associated with microtubule severing at crossover sites in (A) wild type (B qui-2 filament cells. GFP-labeled KTN1 fluorescent particles are pseudo-colored in red, and microtubules (labeled with mCherry-TUB6) are shown in green. Yellow arrows indicate KTN1 at the microtubule crossover sites. Asterisks indicate the location at which a microtubule has been severed at a crossover site in A and B",
    "ncbi_link": "qui-2: 844206///827623///824239///843845///838518"
  },
  {
    "caption": "Time-lapse images showing that KTN1 is associated with microtubule severing at crossover sites C) qui-2 filament cells. GFP-labeled KTN1 fluorescent particles are pseudo-colored in red, and microtubules (labeled with mCherry-TUB6) are shown in green. Yellow arrows indicate KTN1 at the microtubule crossover sites. or the location at which a microtubule has not been severed at a crossover site in C.",
    "ncbi_link": "qui-2: 844206///827623///824239///843845///838518"
  },
  {
    "caption": "(A) GAPC enzymatic activity was measured in wild-type crude extracts treated with H2O (mock), and 100 µM of Tyr-Asp, Tyr, Asp, and  Ile-Glu. (B-D) The enzymatic activities  of GAPC (B), GAPA/B (C), and GAPN  (D) were measured in the wild type and double k.o. mutant gapc1gapc2 treated with  H2O (mock), and 100 µM of Tyr-Asp. Data information: Data are mean ± SEM of n=4 (A-D; four technical replicates) , significance was assessed using unpaired two-tailed Student t-test.",
    "ncbi_link": "gapc1: 819567
gapc2: 837904"
  },
  {
    "caption": "(A-C) Fresh weight  measurements of Arabidopsis wild-type and gapc1/gapc2  double k.o. plants subjected to the oxidative stress (e.g.  catechin) and Tyr-Asp treatments. Each treatment was compared to its respective control, corresponding to plants grown in one 24-well plate (represented by the adjoined bars). (D-F) Representative Arabidopsis wild type and gapc1/gapc2  double k.o. seedlings from the different treatments. All plants were 10-day-old at the stress onset. The seedlings were exposed to  catechin for three days. Data information: Data are mean ± SEM of n=10-12 (seedlings). Unpaired two-tailed Student t-test was performed to compare treatments with control. Scale bar: 10 cm. ",
    "ncbi_link": "gapc1: 819567
gapc2: 837904"
  },
  {
    "caption": "A. Images of HeLa cells stably expressing tubulin-GFP (green) and transiently mRFP-CENP-B (magenta) treated with control siRNA (left images) and siRNA targeting PRC1 (right images). Enlargements of the boxed region, shown to the right of the image of the whole spindle, are focused on kinetochores and bridging fiber (top: merge; middle: GFP, bottom: scheme).",
    "ncbi_link": "PRC1: 9055"
  },
  {
    "caption": "B. Western blot showing PRC1 protein from unlabeled cells, tubulin-GFP HeLa cell line and PRC1-GFP HeLa cell line. Detailed measurements are in Expanded View 4.",
    "ncbi_link": "PRC1: 9055"
  },
  {
    "caption": "C. Mean ratio of signal intensities of the bridging fiber (Ib, measured at the position of a blue line as in scheme) and sum of the bridging and k-fiber (Ibk, measured at the position of the orange line as in scheme), measured in control cells (grey bar) and PRC1 siRNA treated cells (black bar) (p=0.0003).D. Mean interkinetochore distance (dk, see scheme) measured in control cells (grey bar) and PRC1 siRNA treated cells (black bar) (p=0.0001).",
    "ncbi_link": "PRC1: 9055"
  },
  {
    "caption": "F. Mean signal intensity I of the immunostained PRC1 in control cells (grey bar) and PRC1 siRNA treated cells (black bar) in HeLa cells expressing tubulin-GFP and immunostained for PRC1 (p=0.0001).",
    "ncbi_link": "PRC1: 9055"
  },
  {
    "caption": "G. Images of HeLa cells stably expressing PRC1-GFP treated with control (left image) and siRNA targeting PRC1 (right image) immunostained for PRC1 (magenta). Graph showing the length of the immunostained PRC1 signal, LPRC1 (p=0.5167), signal intensity, I (p=0.0003) and Icross (p=0.0001) in siRNA targeting PRC1 in comparison to control HeLa cells expressing PRC1-GFP and immunostained for PRC1.H. Images of HeLa cells stably expressing PRC1-GFP (green) treated with control (left image) and siRNA targeting PRC1 (right image) immunostained for PRC1. Graph showing the length of the PRC1-GFP signal, LPRC1 (p=0.3407), signal intensity, I (p=0.0001), and Icross (p=0.0001) in siRNA targeting PRC1 in comparison to control HeLa cells expressing PRC1-GFP and immunostained for PRC1.",
    "ncbi_link": "PRC1: 9055"
  },
  {
    "caption": " C To determine whether autophosphorylation occurs in cis or trans, autophosphorylation was measured for WT or a kinase dead form of FAK (KD, contains K454R mutation) in presence or absence of a substrate deficient FAK mutant (Y397F) and/or PI(4,5)P2 vesicles. PI(4,5)P2 negative experiments contain control PC vesicles instead. Note that the scales of the two plots are different, i.e. autophosphorylation is increased in presence of PI(4,5)P2. Plotted are mean values from two independent phosphorylation reactions, each determined in duplicates (n=4). Left: Schematic of possible cis- and trans-autophosphorylation (red arrows) in mixtures of FAK-WT/FAK-Y397F and FAK-KD/FAK-Y397F. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " D Src phosphorylation of Y577 in FAK in presence of PC or PI(4,5)P2 vesicles as determined by an ELISA method. The plot on the left is obtained in presence Src containing only the kinase domain (Src254-536) and the plot on the right with Src containing additionally the SH3 and SH2 domains (Src84-536). Plotted are mean values from two independent phosphorylation reactions, each determined in duplicates (n=4). ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " Interactions between WT or interface mutant FAK with a PI(4,5)P2 containing membrane was probed using a pulldown assay with membrane coated silica beads. Plotted are bound protein relative to the binding for WT at the highest PI(4,5)P2 concentration. Mutant naming is as in Table 2. For WT the non-specific binding to a PC membrane is shown for comparison. Plotted are mean values from at least three independent experiments. Error bars: s.d. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " A FAK phosphorylation of WT or interface mutant FAK in SCC cells. Whole cell lysates were subjected to western blot analysis with anti-pFAK Y397, anti-pFAK Y576/577, anti-pFAK Y861, anti-pFAK Y925 and anti-FAK. Anti-GAPDH served as a loading control. The graph shows densitometric analysis of relative pFAK/FAK ratios (mean) from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " B Downstream signaling in SCC cells expressing WT or interface mutant FAK. Whole cell lysates are analyzed by western blot analysis with the indicated antibodies. The graph shows densitometric analysis of relative phospho/total protein ratios (mean) from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": "FAK-expressing SCC cells were grown on glass coverslips, fixed and stained with anti-FAK anti-Paxillin and DAPI Representative immunofluorescence images are shown. Scale bars, 20 μm.",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " B FAK-expressing SCC cells were grown on glass coverslips, fixed and stained with anti-pSrc Y416 , anti-Paxillin and DAPI Representative immunofluorescence images are shown. Scale bars, 20 μm. The graph (B) shows the quantification of internalized active Src from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars, s.d. * = p < 0.01. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " C Subcellular fractionation of SCC cells expressing FAK-WT or interface mutant FAK. Whole cell lysates (WCL) and subcellular fractions were subjected to western blot analysis with anti-FAK, anti-Tubulin (marker for cytoplasmic fraction; C), anti-RCAS (marker for perinuclear fraction; PN) and anti-H4 (marker for nuclear fraction; N). The graph shows densitometric analysis of relative FAK amount of the FAK mutants in the different fractions from three independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars: s.d. * = p < 0.01, # = p < 0.05. For full blots see source data. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " A FAK-WT, interface mutant FAK or FAK -/- SCC cells were resuspended in methylcellulose solution in growth medium on a layer of agarose and observed for 3D sphere formation. Images were taken from 10 random fields after nine days (representative images are shown) and the relative colony size (top graph) as well as the number of colonies (bottom graph) were assessed from three independent experiments. Scale bars, 200 μm. Student's t-test was carried out to calculate the statistical significance. Error bars s.d. * = p < 0.01, # = p < 0.05. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": " B FAK-WT, interface mutant FAK or FAK -/- SCC cells were seeded on growth factor-reduced Matrigel in serum-free media. After 72 h, invasion towards a serum gradient was analyzed by staining the cells with calcein and taking images at 10 μm increments through the matrigel. Representative images of the invasion assay are shown. Scale bars, 200 μm. The graph shows relative invasion from five independent experiments. Student's t-test was carried out to calculate the statistical significance. Error bars, s.e.m. * = p < 0.01, # = p < 0.05. ",
    "ncbi_link": "FAK: 396416"
  },
  {
    "caption": "Example images showing the localization of SOX2-SNAP and OCT4-HALO by fluorescence microscopy of SBROS cells. Scale bar: 50µm.",
    "ncbi_link": "OCT4: 18999"
  },
  {
    "caption": "Correlation between OCT4-HALO and total OCT4 levels determined by immunofluorescence and HALO labelling. R is Pearson's correlation coefficient.",
    "ncbi_link": "OCT4: 18999"
  },
  {
    "caption": "Distributions of OCT4 (n=2682), SOX2 (n=1236) and NANOG (n=2416) levels in WT E14 and SBROS cell lines as determined by quantitative immunofluorescence. Dashed lines: mean protein levels; Dotted lines: median protein levels.",
    "ncbi_link": "OCT4: 18999"
  },
  {
    "caption": "Protein half-lives of OCT4-HALO and SOX2-SNAP in SBROS cells. Whiskers: minimum and maximum values; Box: lower and upper quartiles; Solid line: median. Black dots: outliers.",
    "ncbi_link": "OCT4: 18999"
  },
  {
    "caption": "Endogenous SOX2 levels in single cells (turquoise) normalized to the value at t=0 in SNSF cells upon induction of SOX2-SNAP (n=37, left) or a truncated SOX2 version missing the DNA binding domain (YPET-SOX2-delDBD, n=47, right). Black line: average SOX2-SNAP levels after induction normalized to the maximum level (n=22); Yellow line: average YPET-SOX2-delDBD levels after induction, normalized to the maximum level (n=20).",
    "ncbi_link": "SNAP: 
YPET: 
SOX2: 20674"
  },
  {
    "caption": "Sox2 and Oct4 mRNA levels upon overexpression of YPet-SOX2 or YPET-SOX2-delDBD (n=3). p-values: two-sided t-test with unequal variance.",
    "ncbi_link": "YPet: 
YPET: 
Oct4: 18999
Sox2: 20674
SOX2: 20674"
  },
  {
    "caption": "Changes of OCT4 half-life upon SOX2-SNAP or YPET-SOX2-delDBD overexpression (n=20 cells each). p-values: Mann-Whitney U test. SBROS cells harbouring inducible SOX2-SNAP or YPET-SOX2-delDBD were treated with 0 or 500 ng/ml dox for 6-8 hours followed by pulse-labelling of OCT4-HALO and live-cell imaging.",
    "ncbi_link": "SNAP: 
YPET: 
SOX2: 20674"
  },
  {
    "caption": "Differentiation outcome of uninduced cells or cells induced 12 hours for OCT4-SNAP overexpression before sorting in G1 phase (n=6). p-values: two-sided t-test with unequal variance.",
    "ncbi_link": "SNAP: 
OCT4: 18999"
  },
  {
    "caption": "C. cGAMP-VLPs induce an IFN-I response in target cells. HEK293 cells were infected with decreasing amounts of cGAMP-VLPs and Empty-VLPs (1/5 serial dilutions starting at 2μL of VLP stocks per well) and the infection was monitored 24 hours later by quantifying GFP+ cells by flow cytometry. Supernatants from the same infected cells were then transferred to a reporter cell line expressing firefly luciferase under a promoter induced by IFN-I (ISRE). Luciferase activity measured 24 hours later indicated the presence of IFN-I in the supernatants.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "C. Enhanced antibody production following immunisation with cGAMP-VLPs relies on STING signalling. WT or Sting-/- mice were immunised with PBS, cGAMP-VLPs, Empty-VLPs or Empty-VLPs + poly(I:C). IgG2b antibodies recognising VLP proteins were assessed by ELISA. The optical density at increasing serum dilutions is shown in the first two graphs from the left and the EC50 is on the right.",
    "ncbi_link": "Sting: 72512"
  },
  {
    "caption": "A qRT-PCR analysis of LINC00941 repression during keratinocyte differentiation in primary keratinocyte cultures from three different donors compared to undifferentiated keratinocytes (D0) (n = 6 biological replicates). Data is presented as mean ± SD.",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "siPool mediated LINC00941 knockdown (B) in calcium-induced keratinocyte differentiation (n = 3 biological replicates/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "siPool mediated LINC00941 knockdown in calcium-induced keratinocyte differentiation, results in increased abundance of early and late differentiation marker transcripts on day 3 of differentiation (C) (n = 3 biological replicates/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "LINC00941 knockdown in day 3 (D3) organotypic epidermal tissue cultures (D) (n = 3-4 tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "LINC00941 knockdown in day 3 (D3) organotypic epidermal tissue cultures results in increased expression of key differentiation genes (E) (n = 3-4 tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "B LINC00941 knockdown efficiency (siLINC00941) in epidermal tissue on day 3 of differentiation as obtained by qRT-PCR measurements (n = 4-5 epidermal tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "C Heatmap of differentially expressed genes (padj < 0.05 and -1 > log2FC > 1) upon LINC00941 depletion on day 3 in organotypic epidermal tissue with marked keratinocyte differentiation genes (n = 4-5 epidermal tissue cultures/knockdown group).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "A Differentially expressed genes in day 3 LINC00941 depleted epidermal tissue cluster within the epidermal differentiation complex (EDC) (n = 4-5 biological replicates/knockdown group).",
    "ncbi_link": "LINC00941: 100287314"
  },
  {
    "caption": "B LINC00941 knockdown on day 3 in calcium-induced keratinocyte differentiation cultures results in increased expression of SPRR5 (FC = fold change) (n = 3 biological replicates/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "LINC00941: 100287314
SPRR5: 110806278"
  },
  {
    "caption": "C Detected fragments per million (FPM) for SPRR5 in control (siCtrl) as well as LINC00941 deficient (siLINC00941) epidermal tissue for all biological replicates on day 3 (D3) of differentiation as obtained by DeSeq2 (FC = fold change) (n = 4‑5 epidermal tissue cultures/knockdown group).",
    "ncbi_link": "LINC00941: 100287314
SPRR5: 110806278"
  },
  {
    "caption": "SPRR5 induction during the course of keratinocyte (KC) differentiation is shown by northern blot (D) for four different primary keratinocyte isolates and compared to undifferentiated keratinocytes (n = 8 biological replicates). Data is presented as mean ± SD.",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "SPRR5 induction during the course of keratinocyte (KC) differentiation is shown by qRT-PCR analysis (E) for four different primary keratinocyte isolates and compared to undifferentiated keratinocytes (n = 8 biological replicates). Data is presented as mean ± SD.",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "F p63 knockdown on day 3 of keratinocyte differentiation leads to decreased SPRR5 transcript levels (FC = fold change) (n = 3-4 biological replicates /knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278
p63: 8626"
  },
  {
    "caption": "siPool-mediated SPRR5 knockdown on day 4 to 6 (D4-D6) of calcium-induced keratinocyte differentiation (A) (n = 3-5 cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "siPool-mediated SPRR5 knockdown on day 4 to 6 (D4-D6) of calcium-induced keratinocyte differentiation leads to decreased expression of key differentiation markers as shown by qRT-PCR (B) (FC = fold change) (n = 3-5 cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "siPool-mediated SPRR5 knockdown on day 4 to 6 (D4-D6) of calcium-induced keratinocyte differentiation leads to decreased expression of key differentiation markers as shown western blot analysis (C) (n = 3-5 cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "D SPRR5 knockdown efficiency in day 3 (D3) organotypic epidermal tissue (n = 4 epidermal tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "E SPRR5 depletion in regenerated organotypic epidermal tissue results in drastically reduced expression of differentiation proteins as shown by immunofluorescence analysis. Collagen VII (Col VII, green) stain indicates the basement membrane, nuclei are shown in blue and the differentiation proteins filaggrin and loricrin are shown in red (n = 4 tissue cultures/knockdown group; one exemplary picture for each group is depicted). Scale bar: 50 µm.",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "F SPRR5 knockdown in regenerated epidermal tissue results in reduced transcript levels of key differentiation genes as obtained by qRT-PCR (n = 4 epidermal tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "B Overview of SPRR5 levels in control (siCtrl) and SPRR5 deficient (siSPRR5) epidermal tissue on day 3 and day 4 as obtained by qRT-PCR analysis (n = 3-5 epidermal tissue cultures/knockdown group). Data is presented as mean ± SD. Statistical significance was tested by an unpaired t-test and corrected for multiple testing after Bonferroni (* = adj. p-value < 0.05, ** = adj. p-value < 0.01, *** = adj. p‑value < 0.001, and n.s. = not significant).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "Heatmaps of differentially expressed genes (padj < 0.05 and -0.5 > log2FC > 0.5) upon SPRR5 depletion on day 3 (C) in organotypic epidermal tissue (n = 3-5 epidermal tissue cultures/knockdown group).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "Heatmaps of differentially expressed genes (padj < 0.05 and -0.5 > log2FC > 0.5) upon SPRR5 depletion on day 4 (D) in organotypic epidermal tissue (n = 3-5 epidermal tissue cultures/knockdown group).",
    "ncbi_link": "SPRR5: 110806278"
  },
  {
    "caption": "(c) UVRAG binds Beclin1 through its CCD. After transfection with Beclin1-V5, together with full-length or fragments of Flag-UVRAG, 293T whole cell lysates (WCLs) were used for immunoprecipitation (IP) with anti-Flag followed by immunoblotting (IB) with anti-V5.",
    "ncbi_link": "Beclin1: 8678
UVRAG: 7405"
  },
  {
    "caption": "(e) UVRAGCCD is required for Beclin1 interaction. After transfection with Beclin1-V5 (lanes 2 and 4) together with Flag-UVRAGΔCCD (lanes 1 and 2) or Flag-UVRAGΔC2 (lanes 3 and 4), WCLs were used for immunoprecipitation with anti-Flag followed by immunoblotting with anti-V5.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(f) Beclin1 binds UVRAG through its CCD. After transfection with Flag-UVRAG together with full-length or fragments of Beclin1-V5, WCLs were used for immunoprecipitation with anti-V5 followed by immunoblotting with anti-Flag.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(a) The Bcl-2 binding domain of Beclin1 is sufficient to bind vBcl-2. At 48 h posttransfection with wild-type and mutant Beclin1-V5, together with HA-vBcl-2, WCLs of 293T cells were used for immunoprecipitation with anti-V5 followed by immunoblotting with anti-HA.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(b) The loss of Beclin1 interaction of vBcl-2AAA mutant. At 48 h posttransfection with wild-type HA-vBcl-2 or vBcl-2AAA mutant, together with Beclin1-V5, WCLs of 293T cells were used for immunoprecipitation with anti-V5, followed by immunoblotting with anti-HA.",
    "ncbi_link": "Bcl-2: 596"
  },
  {
    "caption": "(c) vBcl-2 interaction with wild-type UVRAG in the presence of Beclin1. At 48 h posttransfection with Flag-UVRAG together with Beclin1-V5 and HA-vBcl-2 or vBcl-2AAA mutant, WCLs of 293T cells were used for immunoprecipitation with anti-HA followed by immunoblotting with anti-Flag.",
    "ncbi_link": "Bcl-2: 596"
  },
  {
    "caption": "(e) PI(3)KC3 N-terminal C2 domain binds Beclin1. At 48 h posttransfection with Beclin1-V5 together with full-length or fragments of Flag-PI(3)KC3, WCLs of 293T cells were used for immunoprecipitation with anti-Flag followed by immunoblotting with anti-V5. CAT, catalytic domain.",
    "ncbi_link": "PI(3)KC3: 5289"
  },
  {
    "caption": "(f) Beclin1CCD and Beclin1ECD are sufficient for binding PI(3)KC3. At 48 h posttransfection with Flag-PI(3)KC3 together with full-length or fragments of Beclin1-V5, WCLs of 293T cells were used for immunoprecipitation with anti-V5 followed by immunoblotting with anti-Flag. CT, C terminus (aa 337-448).",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(g) PI(3)KC3 interaction with UVRAG in the presence of Beclin1. At 48 h posttransfection with Flag-UVRAGΔCCD or UVRAGCCD together with HA- PI(3)KC3 and Beclin1-V5, WCLs of 293T cells were used for immunoprecipitation with anti-Flag followed by immunoblotting with anti-HA.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) UVRAG expression and LC3 process in HCT116 cells. The same protein amounts of 293T, NIH3T3, HCT116 and MCF7 cells were used for immunoblotting with anti-UVRAG and anti-tubulin. WCLs of 293T cells transfected with Flag-tagged UVRAG were included as controls. WCLs of HCT116.vector and HCT116.UVRAG were incubated with or without starvation conditions and used for immunoblotting with anti-LC3 and anti-tubulin. The raw data for this experiment is presented in the Supplementary information, Fig. S5.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) Electron microscopy of autophagy in HCT116 cells. HCT116.vector and HCT116.UVRAG cells were incubated under normal or starvation conditions for 4 h and subjected to scanning electron microscopy. Scale bars (from left to right panels) represent 2 nm, 0.5 nm, 0.2 nm and 0.2 nm. The arrows indicate autophagosome or autolysosome.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) UVRAG induces autophagosome formation in HCT116 cells. After transfection with GFP-LC3 vector, HCT116.vector and HCT116.UVRAG cells were maintained under normal conditions or starved for 3 h. GFP-LC3 was detected using an inverted fluorescence microscope. Arrows indicate autophagosomes. The scale bars represent 10 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(d) After transfection with GFP-LC3 vector, HCT116.vector and HCT116.UVRAG cells were maintained under normal conditions, starved for 3 h in the absence or presence of 10 mM 3-methyladenine or treated with or without 2 μM rapamycin or rapamycin + 10 mM 3-methyladenine. Autophagome was quantified as the mean ± s.d. of combined results from three independent experiments.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) HCT116.vector and HCT116.UVRAG cells were labelled with LysoTracker and subjected to flow cytometry analysis. HCT116.vector, HCT116.UVRAG, and HCT116.UVRAG ΔCCD cells were treated with or without wortmannin (1 μM) for 2 h and their lysates were used to measure the lysosomal acid phosphatase enzymatic activity. Data represents mean ± s.d. of three experiments.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) UVRAG induces autophagosome formation in NIH3T3 cells. After transfection with GFP-LC3 vector, NIH3T3.vector and NIH3T3.UVRAG cells were maintained under normal conditions, starved for 3 h in the absence or presence of 10 mM 3-methyladenine or treated with or without 2 μM rapamycin or rapamycin + 10 mM 3-methyladenine. Data represents mean ± s.d. of three experiments.",
    "ncbi_link": "UVRAG: 78610"
  },
  {
    "caption": "(a) Autophagic activity of UVRAG mutants. HCT116 cells expressing wild-type or mutant UVRAG were transfected with GFP-LC3 expression vector and incubated under normal or starvation conditions for 3 h. Autophagy was quantified as described in Fig. 3.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) Effect of wild-type and mutant UVRAG on Beclin1-mediated autophagy. MCF7.vector, MCF7.Beclin1 and MCF7.Beclin1ΔECD cells were cotransfected with wild-type UVRAG or its mutant expression vector together with GFP-LC3 expression vector. At 16-18 h posttransfection, cells were incubated under normal or starvation conditions for 4 h. Autophagy was quantified as described in Fig. 3. The scale bars represent 20 μm.",
    "ncbi_link": "Beclin1: 8678
UVRAG: 7405"
  },
  {
    "caption": "(c, d) Interdependence between UVRAG and Beclin1 for autophagosome induction. HCT116.vector and HCT116.UVRAG cells were transfected with control siRNA, Beclin1 siRNA or UVRAG siRNA together with GFP-LC3 expression vector as indicated. Autophagy was quantified as described in Fig. 3. WCLs of these cells were used for immunoblotting with anti-UVRAG, anti-Beclin1 or anti-tubulin. The scale bars represent 20 μm. In all figures, data represents mean ± s.d. of three experiments. The raw data for c and d are presented in the Supplementary Information, Fig S5.",
    "ncbi_link": "Beclin1: 8678
UVRAG: 7405
UVRAG: 78610///7405"
  },
  {
    "caption": "(c, d) Interdependence between UVRAG and Beclin1 for autophagosome induction.MCF7.vector, MCF7.Beclin1 and MCF7.Beclin1ΔECD cells (d) were transfected with control siRNA, Beclin1 siRNA or UVRAG siRNA together with GFP-LC3 expression vector as indicated. Autophagy was quantified as described in Fig. 3. WCLs of these cells were used for immunoblotting with anti-UVRAG, anti-Beclin1 or anti-tubulin. The scale bars represent 20 μm. In all figures, data represents mean ± s.d. of three experiments. The raw data for c and d are presented in the Supplementary Information, Fig S5.",
    "ncbi_link": "Beclin1: 8678
UVRAG: 7405"
  },
  {
    "caption": "(a) Increased Beclin1-PI(3)KC3 interaction by UVRAG and continued interaction of UVRAG with Beclin1 on stress conditions. HCT116.vector, HCT116.UVRAG and HCT116.UVRAGΔCCD cells were used for immunoprecipitation with anti-PI(3)KC3 followed by immunoblotting with anti-Beclin1. WCLs were used for immunoblotting with anti-Beclin1 and anti-PI(3)KC3. HCT116.UVRAG cells expressing Flag-tagged UVRAG were incubated under nutrient-rich conditions (lanes 1 and 2), starvation for 4 h (lane 3), or 2 μM rapamycin treatment for 2 h (lane 4). WCLs were then used for immunoprecipitation with anti-Beclin1 (lanes 2, 3 and 4) or preimmune antibody (lane 1) followed by immunoblotting with anti-Flag. The raw data for this experiment are presented in the Supplementary Information, Fig. S5.",
    "ncbi_link": "UVRAG: 78610///7405"
  },
  {
    "caption": "(b) Increased PI(3)KC3 activity by UVRAG. At 48 h posttransfection with Flag-tagged PI(3)KC3 with Beclin1 (lane 1), with Beclin1 + UVRAG (lane 2) or with Beclin1 + UVRAGΔCCD vector (lane 3), WCLs of 293T cells were used for immunoprecipitation with anti-Flag followed by an assay for PI(3)KC3 lipid kinase activity, as described in the Methods. At 16 h posttransfection with p40(phox) PX-EGFP fusion, HCT116.vector and HCT116.UVRAG cells were detected using an inverted fluorescence microscope. p40(phox) PX-EGFP-positive vesicles were quantified as the mean ± s.d. of combined results from three independent experiments. The scale bars represent 10 μm.",
    "ncbi_link": "p40(phox): 5594
UVRAG: 78610///7405"
  },
  {
    "caption": "(c) Suppression of autophagy by γHV68 vBcl-2. At 18 h posttransfection with GFP-LC3 vector, NIH3T3.vector, NIH3T3.vBcl-2 and NIH3T3.vBcl-2AAA, cells were incubated under normal or starvation conditions for 4 h. Subsequently, GFP-LC3 was detected using an inverted fluorescence microscope and autophagy was quantified as mean ± s.d. of combined results from three independent experiments.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(a) Proliferation rates. HCT116.vector, HCT116.UVRAG, HCT116.UVRAGΔC2, HCT116.UVRAGΔCCD and HCT116.UVRAGCCD cells (1 × 105 per well) were seeded into 6-well microtitre plates. Cell numbers were counted on the days indicated. The results represent means of three independent assays.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) Anchorage independence. HCT116.vector, HCT116.UVRAG, HCT116.UVRAGΔC2, HCT116.UVRAGΔCCD and HCT116.UVRAGCCD cells (1 × 104) were incubated in soft agar as described in the Methods. After ten days, colonies were photographed and counted. The scale bars represent 50 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) Tumorigenicity. HCT116.vector, HCT116.UVRAG and HCT116.UVRAGΔCCD cells (1 × 107) were subcutaneously injected into 5 nude mice, separately. At 16 days postinoculation, mice and tumours were photographed and tumour weights were measured. Arrows indicate location of tumours.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "B Typical dsDNA processing event. The dashed red line connects the minima at the end of the rewinding sections The inset shows a DNA unwinding event in the presence of nuclease-dead Dna2 E675A and RPA.",
    "ncbi_link": "Dna2: 856569"
  },
  {
    "caption": "(A) CRISPR-guided  AID∆C protein could support CSR   in  Aicda-/- CH12F3  cells. Left, CRISPR-guided AID   is schematically illustrated with each component listed. Right, CRISPR-guided AID   initiated CSR   levels to IgA. Blue arrows represent multiple CRISPR  recognition sites. The number in the parentheses indicates CRISPR  recognition sites in each S region. Three biological replicates are plotted by dots and mean with standard deviation (SD). Data information: For panels A one-way ANOVA followed by Dunnett's multiple comparisons test was used for significance assessment. For all panels, ****, p<0.0001; ***, p<0.001; **, p<0.01; *, p<0.05; ns, p>0.05.",
    "ncbi_link": "CRISPR: 
Aicda: 11628
AID: 11628"
  },
  {
    "caption": "(B) CRISPR-guided AID  generated breaks  at the S region in Aicda-/- CH12F3  cells were quantitatively detected by  PEM-seq. Top, schematic illustration shows the bait SaCas9 site at Iγ3  region and CRISPR-guided AID  variants targeting sites at S regions. Bottom, percentages of translocation junctions between Iγ3  and Sμ  or Sα  regions are plotted as mean with SD of three biological replicates in the bar plot. Data information: For panels B, one-way ANOVA followed by Dunnett's multiple comparisons test was used for significance assessment. For all panels, ****, p<0.0001; ***, p<0.001; **, p<0.01; *, p<0.05; ns, p>0.05.",
    "ncbi_link": "Cas9: 
CRISPR: 
Aicda: 11628
AID: 11628"
  },
  {
    "caption": "(C) AID-AIDE58Q dimer proteins were expressed in AID-deficient CSR-activated  B cells, AID   dimer is schematically illustrated on top and CSR  levels to IgG1  are shown. Three biological replicates are plotted by dots and mean with SD is shown. Data information: For panels C, one-way ANOVA followed by Dunnett's multiple comparisons test was used for significance assessment. For all panels, ****, p<0.0001; ***, p<0.001; **, p<0.01; *, p<0.05; ns, p>0.05.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(D) CSR  levels to IgA  in Aicda-/- CH12F3-miniS  cells with indicated AID  variants or CRISPR-guided AID  variants. Levels of CSR  to IgA  are plotted and mean with SD of three to six biological replicates. Data information: Unpaired two-tailed Student's t-test was performed for panel D. For all panels, ****, p<0.0001; ***, p<0.001; **, p<0.01; *, p<0.05; ns, p>0.05.",
    "ncbi_link": "CRISPR: 
Aicda: 11628
AID: 11628"
  },
  {
    "caption": "(E) Mutation profiles  of miniS  region in Ung-/-Msh2-/-Aicda-/- miniS  cell lines complemented with indicated AID. Mutation frequency at each nucleotide along the 756-bp miniS region  is plotted as a bar graph with green error bars, representing mean with standard error of the mean (SEM) of three biological replicates. Positions of AID-preferred AGCT  and other RGYW  motifs are marked with orange and yellow respectively under each plot.",
    "ncbi_link": "Aicda: 11628
AID: 11628
Msh2: 17685
Ung: 22256"
  },
  {
    "caption": "(F)   Mutation profiles of  miniS region in Ung-/-Msh2-/-Aicda-/- miniS  cell lines expressing CRISPR-guided AID  variants. Mutation frequency at each nucleotide is plotted as mean with SEM of three biological replicates in the bar graph with green error bar. Plots are labeled as in (B). The sgRNA targeting position is indicated with blue lines at the bottom.",
    "ncbi_link": "CRISPR: 
Aicda: 11628
AID: 11628
Msh2: 17685
Ung: 22256"
  },
  {
    "caption": "(A) Representative images showing the localization  of AID  (green), AIDR190X (green), and endogenous IgH loci (red) in nucleofected Aicda-/- CH12F3  cells. The IgH   loci are visualized using Sμ-gRNA and indicated by white arrows. An illustration of CRISPR-Sirius IgH  locus visualization is shown on top. Scale bar, 5 µm.",
    "ncbi_link": "CRISPR: 
Aicda: 11628
IgH: 111507"
  },
  {
    "caption": "(B) OptoDroplet  formation in CH12F3  cells. Schematic illustration of light-induced optoDroplet  system is depicted on top. AID  variants were tagged to the N terminus of the optoDroplet  construct and blue light was employed to promote the formation of puncta three times followed by imaging  each time. Representative images after the third blue light activation in Aicda-/- CH12F3  cells with the indicated AID  variants are shown at the bottom. White dashed line and green line depict the shapes of nucleus  and nucleolus  based on Hoechst staining  or GFP-FBL, respectively. Scale bar, 5 µm.",
    "ncbi_link": "Aicda: 11628
AID: 11628"
  },
  {
    "caption": "(C) Representative images showing optoDroplet  formation of indicated AID  variants in HEK293T  cells. CRM1  inhibitor (CRM1i) was used for selective trapping of AID  in nuclei. Scale bar, 5 µm.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(F) Formation of puncta in primary B cells complemented with AID-FUS-GFP  or AID-FUSm-GFP. FUSm contains 13 mutations on either Y or R residue. Left: Representative images showing cellular localization  of AID-FUS-GFP  and AID-FUSm-GFP  with and without CRM1  inhibitor (CRM1i) treatment in Aicda-/- primary B cells. Scale bar, 5 µm. Right: Quantification of the number of cells with condensed puncta (3 biological replicates). Unpaired two-tailed Student's t-test was performed. ****, p<0.0001.",
    "ncbi_link": "GFP: 
Aicda: 11628
AID: 11628
FUS: 233908"
  },
  {
    "caption": "(G) CSR  levels to IgG1   in activated Aicda-/- primary B cells complemented with the indicated protein. Left, representative flow cytometry plots measuring CSR  to IgG1. Co-expressed GFP  was used to indicate the infected fractions. Right, the mean with SD of three biological replicates is shown in the bar plot. Unpaired two-tailed Student's t-test was performed. ****, p<0.0001.",
    "ncbi_link": "Aicda: 11628"
  },
  {
    "caption": "(A) Representative immunofluorescence  images of endogenous AID  in the presence of ectopically-expressed EV, AID, AIDR190X, or AIDcry in cytokine-stimulated CH12F3  cells. EV, empty vector control. An antibody against AID   C terminus (185-198 aa) detected both endogenous and ectopically-expressed full-length AID. The nucleolus  is indicated by co-nucleofected mCherry-FBL. The white dashed line depicts the shape of the nucleus  based on Hoechst staining. Arrows indicate the location  of puncta formed by endogenous AID. The images were taken by the N-SIM microscope and processed via N-SIM software. A middle slice of the images was shown. Scale bar, 5 µm.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(B)  Co-condensation  of AID  and AIDR190X in the nucleus  of CH12F3  cells in the early G1 phase. Top: experimental layout. GFP-tagged wild-type AID  (green) and mCherry-tagged AID  variants (red) were co-nucleofected in Aicda-/- CH12F3  cells. The resulting cells were arrested with nocodazole  for 12 hours after transfection. Six hours later, nocodazole  was removed from the system for 1.5 hours before imaging. Bottom left: representative images showing subcellular localization  of indicated AID  variants. The white dashed line depicts the shape of the nucleus  based on Hoechst staining. The white arrow indicates the location  of the co-condensed puncta. Scale bar, 5 µm. Bottom right: plot profiles of the images. Cyto: cytoplasm, Nuc: nucleus.",
    "ncbi_link": "GFP: 
mCherry: 
Aicda: 11628
AID: 11628"
  },
  {
    "caption": "(D) Dynamics of trapping of wild-type AID  in optoAIDR190X condensates. Top, representative fluorescence images at different time points. Dashed circles indicate the co-condensed  puncta formation of AID-GFP. Scale bar, 5 µm. Bottom, a summary of 12 observed cells is shown as mean ±SD in a bar graph. Percentages of  optoAIDR190X puncta with trapped wild-type AID  are plotted for the second and third blue-light activations, and the colored dot indicates one cell.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(B) The optoDroplet  formation of indicated AID  mutants along with light  stimulation. Top, the procedure of optoDroplet  assay is illustrated with indicated light  stimulation (blue arrow) and image acquisition (black arrow) time points. Bottom, line plots show quantification of cells with optoDroplet  formation as mean ± SD at each acquisition  time point. The total acquired cell numbers of each genotype are indicated in parentheses. Significance assessment between AIDR190X and AIDR190X-4R was shown at each  time point. Unpaired two-tailed Student's t-test was performed. ****, p<0.0001.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(C) CSR  levels of ectopically-expressed AID variants in AID-proficient CH12F3  cells. Left, representative flow cytometry plots of CSR  to IgA. Co-expressed GFP  indicates the infected cell fractions. Right, the CSR  mean with SD of three biological replicates is shown in the bar plot. (D) CSR  levels of ectopically-expressed AID   variants in CSR-activated B cells. Left, representative flow cytometry plots of CSR  to IgG1. Right, the bar plot shows the CSR  mean with SD of four biological replicates. Data information: One-way ANOVA followed by Dunnett's multiple comparisons test was performed for (C) and (D). ***, p<0.001; **, p<0.01; *, p<0.05.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "(B) CSR  to IgA  induced by AID  variants in CH12F3  cells. Left, representative  flow cytometry plots. Right, the CSR  mean with SD of three biological replicates is shown in the bar plot. One-way ANOVA followed by Dunnett's multiple comparisons test was performed. ***, p<0.001; **, p<0.01.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "A. Anterior and lateral photographs of two patients  with ELP6  variants showing dysmorphic features at 20 (Patient  2) and 19 (Patient  3) years of age.",
    "ncbi_link": "ELP6: 54859"
  },
  {
    "caption": "B. Mid-sagittal (I), coronal  (II) and transversal  (III) MRI  scans of Patient  1 with newly identified ELP4  variants and Patient  2 and Patient  3 with ELP6  variants. Atrophy  of the cerebellum  with prominence of the cerebellar folia is marked by circles. Arrows indicate thin corpus callosum, red arrowheads point to enlarged extra-axial CSF  spaces and black arrowheads to cerebral sulci in keeping with cerebral  and cerebellar  volume loss.",
    "ncbi_link": "ELP4: 26610
ELP6: 54859"
  },
  {
    "caption": "D. Co-immunoprecipitation  analyses of Elongator complexes in patient-derived fibroblast  cell. Whole cell lysates (left) and eluates after  immune-precipitation (right) are shown for control fibroblasts  (ctrl) and cultured patient fibroblasts  (Elp4Y91C/L296I (patient  1); Elp6L118W/L118W (patient  2),  Elp6L118W/L118W (patient  3). Used antibodies for immobilization (ELP1) and detection (ELP1, ELP3, ELP4  , ELP5  and α-tubulin) are indicated. n = 4 independent experiments.",
    "ncbi_link": "Elp4: 26610
Elp6: 54859"
  },
  {
    "caption": "F. Differential expression  (DE) of peptides in fibroblasts  obtained from the individuals with ELP4  and ELP6  variants relative to control (n = 3 technical repeats per genotype). Down- (red) and upregulated (blue) peptides are depicted on volcano plots.",
    "ncbi_link": "ELP4: 26610
ELP6: 54859"
  },
  {
    "caption": "The relative abundance of CggR (normalized to the abundance measured on glucose and the same promoter) is almost constant with PTEFmut7 across multiple growth rates in WT and TM6 cells, but not with PTEFmut2 and PCMV. The CggR intracellular levels were quantified by proteomics in steady-state cultures grown in minimal media with glucose, galactose, maltose or pyruvate as carbon sources at a final concentration of 10 gL-1. WT data includes all three promoters, whereas TM6 only includes the PTEFmut2 and PTEFmut7 data. Error bars represent the standard deviation of at least three replicate experiments.",
    "ncbi_link": "CMV: 
TEF: 856195"
  },
  {
    "caption": "The four reporter plasmids were transferred to the wildtype strain containing the CggR (R250A) under the control of the PTEFmut7. The strength of the four promoters was assessed by quantifying YFP (FL1) and mCherry (FL3) fluorescence in exponentially growing wildtype cells in minimal medium with 10 g l-1 glucose. The FL1 and FL3 fluorescence shown is the non-background corrected median of 100 000 cell events. The non-FL control is the signal from a wildtype strain grown under the same conditions. The background fluorescence, assessed by the wildtype harboring the YCplac33 plasmid, was substracted from FL1 and FL3. The final reporter activity is the ratio of the background-corrected YFP and mCherry values. Error bars represent the standard deviation of three independently determined ratios from three replicate experiments.",
    "ncbi_link": "mCherry: 
YFP: 
CggR: 938570
TEF: 856195"
  },
  {
    "caption": "Reporter activity of the sensor across (D) multiple FBP levels Reporter activity is given by the YFP/mCherry ratio, calculated through the quantification of YFP and mCherry fluorescence along culture time using flow cytometry. Both YFP and mCherry fluorescence levels were first corrected for background using the same strains harboring the YCplac33 plasmid (Appendix Table S8). The control is the wildtype and TM6 strains expressing only the reporter plasmid without CggR. Error bars represent the standard deviation of at least three replicate experiments.",
    "ncbi_link": "mCherry: 
YFP: 
CggR: 938570"
  },
  {
    "caption": "Reporter activity of the sensor across glycolytic fluxes. The glycolytic flux is reported as the flux between the metabolites fructose 6-phosphate (F6P) and fructose-1,6-bisphosphate (FBP). Glycolytic fluxes were here estimated on the basis of physiological and metabolome data and a novel method to estimate intracellular fluxes (Niebel et al, 2019). Reporter activity is given by the YFP/mCherry ratio, calculated through the quantification of YFP and mCherry fluorescence along culture time using flow cytometry. Both YFP and mCherry fluorescence levels were first corrected for background using the same strains harboring the YCplac33 plasmid (Appendix Table S8). The control is the wildtype and TM6 strains expressing only the reporter plasmid without CggR. Error bars represent the standard deviation of at least three replicate experiments.",
    "ncbi_link": "mCherry: 
YFP: 
CggR: 938570"
  },
  {
    "caption": "Sub-populations of WT and TM6 cells, grown separately and mixed in different fractions as indicated in percentages, can easily be distinguished by flow cytometry, FL1 YFP channel, FL3 mCherry channel. Histogram of single-cell ratios of FL1/FL3 fluorescence intensities of mixed WT and TM6 populations analyzed by flow cytometry. Here, a sub-population of minimally 5% can be distinguished.",
    "ncbi_link": "mCherry: 
YFP: "
  },
  {
    "caption": "Tukey boxplots showing the YFP/mCherry ratio of individual cells measured by microscopy as a function of glycolytic flux. At least 35 cells were analyzed in each condition. The glycolytic flux is here reported as the flux between the metabolites fructose 6-phosphate (F6P) and FBP. Glycolytic fluxes were estimated on the basis of physiological and metabolome data and a novel method to estimate intracellular fluxes (Niebel et al, 2019).",
    "ncbi_link": "mCherry: 
YFP: "
  },
  {
    "caption": "YFP/mCherry ratio measured by microscopy in co-existing dividing (high-flux) versus non-dividing (low-flux) isogenic TM6 cells on 10 gL-1 glucose.",
    "ncbi_link": "mCherry: 
YFP: "
  },
  {
    "caption": "The production rates of YFP and mCherry are uncoupled during the cell cycle in the biosensor-expressing strain (F), which reflects the cell-cycle dynamics of intracellular FBP concentration and glycolytic flux. In a control strain, lacking CggR, the production rates of YFP and mCherry are coupled (G). The uncoupling was calculated for individual cell-cycle trajectories as the difference between the YFP and mCherry production rates normalised to have the same scale (see more details in Materials and methods; Appendix Figure S10). Each curve represents the mean across the indicated number of cell cycles in a replicate experiment. The corresponding shaded areas denote the 95% confidence intervals of the means (bootstrapping with 5 000 iterations). We smoothed the single-cell-cycle trajectories of YFP and mCherry signals as well as cell volume via the Gaussian process regression, and used these trajectories to derive the YFP and mCherry production rates, accounting for fluorescent-protein maturation in a first-order kinetics model. To align the cell-cycle trajectories and to calculate the phase, we used the array of three cell cycle events E {cytokinesis (cyt), budding, next cyt} as reference points. The cell cycles used for the analysis had the duration in the interval between 150 and 300 minutes, with the mean duration presented in parentheses for each replicate experiment. The cells belonged to the TM6 strain and were cultivated on 20 gL-1 glucose in the microfluidic device.",
    "ncbi_link": "mCherry: 
YFP: 
CggR: 938570"
  },
  {
    "caption": "Bisulfite sequence analysis of DMRs of the imprinted genes (PEG1, KvDMR1, PEG10, and NESP55) in iPSCs (top) and d6 TRA‐1‐81+/cKIT+ PGCLCs (bottom). White and black circles represent unmethylated and methylated CpG sequences, respectively.",
    "ncbi_link": "NESP55: 2778
KvDMR1: 10984
PEG1: 4232
PEG10: 23089"
  },
  {
    "caption": "Effect of knockdown of BLIMP1 and PRDM14 on PGCLC induction. Knockdown of BLIMP1 (F) and PRDM14 (G) was done using the lentiviral system with two individual shRNA vectors for each gene. The knockdown efficiencies were assessed by qPCR (left panel, each). The induction of d4 PGCLCs analyzed by FACS, gated for TRA‐1‐81 and cKIT (right panel, each). Data are presented as means ± SD (n = 3).",
    "ncbi_link": "BLIMP1: 639
PRDM14: 63978"
  },
  {
    "caption": "Spleen, mLN, sdLN, liver, adipose, and lung lymphocytes from Jα18-/- or Vα14 mice were stimulated in vitro with RAW-CD1d cells and 1μg α-GalCer. An additional sample of Vα14 lymphocytes from each organ was plated with RAW-CD1d cells but no α-GalCer. Supernatants were collected after 24 hours and cytokine concentration determined by cytokine bead array. Error bars are SD of mean values from three different mice per group. Results shown are representative of two independent experiments where n=3 biological replicates.",
    "ncbi_link": "CD1d: 12479///12480
Jα18: 100124371
Vα14: 100126466"
  },
  {
    "caption": "Lymphocytes from the indicated tissues of C57BL/6 and Vα14 mice were stained with anti-CD3 and CD1d (PBS57) tetramer, before they were fixed, permeabilized, and stained with antibodies to T-bet, RORγt, and PLZF. Results shown are gated on CD3+CD1d-tetramer+ cells.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Lymphocytes from the Peyer's patches of C57BL/6 and Vα14 mice were stained with anti-CD3 and CD1d (PBS57) tetramer. Percentage of lymphocytes that were CD3+CD1d-tetramer+ iNKT cells among the Peyer's patches of C57BL/6, Vα14, and Jα18-/- mice are shown. Mann-Whitney test. Error bars are SD. C57BL/6 n=22; Vα14 n=16; Jα18-/- n=8.",
    "ncbi_link": "Jα18: 100124371
Vα14: 100126466"
  },
  {
    "caption": "(C-E)Mice were analyzed for total fecal IgA by ELISA. Mann-Whitney test. Error bars are SD. C57BL/6 n=14; Vα14 n=11; Jα18-/- n=13.",
    "ncbi_link": "Jα18: 100124371
Vα14: 100126466"
  },
  {
    "caption": "(C-E)Mice were analyzed for total fecal IgG1 (D) or total serum IgG1 (E) by ELISA. Mann-Whitney test. Error bars are SD. C57BL/6 n=14; Vα14 n=11; Jα18-/- n=13.",
    "ncbi_link": "Jα18: 100124371
Vα14: 100126466"
  },
  {
    "caption": "Percentages of total B cells that were IgG1+ in the spleen, mLN, and Peyer's patches of C57BL/6, Vα14, and Jα18-/- mice are shown. Mann-Whitney test. Error bars are SD. C57BL/6 n=15; Vα14 n=15; Jα18-/- n=5",
    "ncbi_link": "Jα18: 100124371
Vα14: 100126466"
  },
  {
    "caption": "CD1d (PBS57) tetramer+ CD3+ cells were sorted from spleens or PP of 3 different Vα14 TN mice along with CD4+CD3+CD1d tetramer- cells from PP (PP CD4). RNAseq was performed. Heatmap of FPKM values for the indicated Tfh genes across each RNAseq sample.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Spleen, mLN, and PP lymphocytes from Vα14 and C57BL/6 mice were stimulated with PMA and ionomycin. Lymphocytes were stained with anti-CD3, CD1d (PBS57) tetramer, anti-IL-4, and anti-IFNγ. Percentages of iNKT cells and non-iNKT T cells within the population of CD3+IL-4+ cells and CD3+IFNγ+ cells, n = 5 mice for C57BL/6 group and n = 4 mice for Vα14 group. Error bars are SD.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Vα14 TN mice were administered α-GalCer either 2μg intravenously or 5μg by oral gavage. Mice were given Brefeldin A intraperitoneally after 30 min, and tissues were harvested 3 hours later. Cells from spleen, mesenteric lymph node, and Peyer's patches of Vα14 TN mice were permeabilized, fixed, and stained with antibodies to IL-4, IFNγ, and IL-17. Plots shown are gated on CD1d-(PBS57)-tetramer+ CD3+ iNKT cells.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Pooled spleen and LN cells from a Vα14 TN mouse were cocultured with wild type B cells with or without 1μg α-GalCer and with or without agnostic anti-CD40. IgM was measured by ELISA of culture supernatants 4 days later.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Pooled spleen and LN cells from a Vα14 TN mouse were cocultured with anti-CD40 activated wild type B cells with or without 1μg α-GalCer and with blocking antibody to CD1d (1μg/mL, clone 1B1) or isotype control as indicated. IgM, IgG1, and IgA were measured by ELISA of 4 day culture supernatants.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Spleen, mLN or PP cells from Vα14 TN iNKT mice and PP cells from an IL-4-/- mouse were cocultured with anti-CD40 activated wild type or CD1d-/- B cells. 1μg α-GalCer was added to the cultures to specifically activate iNKT cells. IL-4 were measured by ELISA of culture supernatants.",
    "ncbi_link": "CD1d: 12480///12479
IL-4: 16189
Vα14: 100126466"
  },
  {
    "caption": "Spleen, mLN or PP cells from Vα14 TN iNKT mice and PP cells from an IL-4-/- mouse were cocultured with anti-CD40 activated wild type or CD1d-/- B cells. 1μg α-GalCer was added to the cultures to specifically activate iNKT cells. Blocking antibodies to IL-4 or isotype were added as indicated. IgG1 (D-E) were measured by ELISA of culture supernatants.",
    "ncbi_link": "CD1d: 12480///12479
IL-4: 16189
Vα14: 100126466"
  },
  {
    "caption": "Spleen, mLN or PP cells from Vα14 TN iNKT mice and PP cells from an IL-4-/- mouse 1μg α-GalCer was added to the cultures to specifically activate iNKT cells. Blocking antibodies to IL-4 or isotype were added as indicated. IgG1+ and IgA+ class switched B cells were enumerated by flow cytometry after 4 days of coculture",
    "ncbi_link": "IL-4: 16189
Vα14: 100126466"
  },
  {
    "caption": "Spleen, mLN or PP cells from Vα14 TN iNKT mice and PP cells from an IL-4-/- mouse were cocultured with anti-CD40 activated wild type or CD1d-/- B cells. 1μg α-GalCer was added to the cultures to specifically activate iNKT cells. Blocking antibodies to IL-4 or isotype were added as indicated. IgG1+ class switched B cells were enumerated by flow cytometry after 4 days of coculture",
    "ncbi_link": "CD1d: 12480///12479
IL-4: 16189
Vα14: 100126466"
  },
  {
    "caption": "Cells from spleen, mesenteric lymph node, and Peyer's patches of Vα14 TN mice were permeabilized, fixed, and stained with the indicated antibodies. Plots shown are gated on CD1d-(PBS57)-tetramer+ CD3+ iNKT cells. Quantification of data from E, n=3 mice per group. Mann-Whitney test. Error bars are SEM. *p<0.05.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "Spleen and PP cells from Vα14 TN mice were stained with the indicated antibodies, analyzed by flow cytometry and gated on CD1d (PBS57) tetramer+CD3+ cells.",
    "ncbi_link": "Vα14: 100126466"
  },
  {
    "caption": "(A) Immunoblot  showing the activation of PI3K/AKT  pathway (by assessing the levels of p-AKT Ser473) of ECs 24h after induction of Pik3caH1047R expression.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B) Volcano plot of genes analysed by RNAseq in ECs  upon Pik3caH1047R expression. Differentially expressed genes (DEGs) (p adj < 0.05) in Pik3caH1047R over Pik3caWT ECs  at 24h (grey, unchanged; orange, downregulated; purple, upregulated). n=4 biological replicates per genotype.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(D) Immunoblot  showing the activation of PI3K/AKT  pathway of  Pik3caWT and Pik3caH1047R ECs  after 2h starvation   (-) and 30 min stimulation with 20%  fetal bovine serum (FBS) (+).",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(E, F) (E)  Cell cycle analysis  by flow cytometry  of  Pik3caWT and Pik3caH1047R ECs  after cultured either without serum  (-) or 20% serum  (+) for 24h. (F) Percentage of proliferative ECs  (in S and  G2M  phases) from Fig 1E. Error bars are s.e.m. n ≥ 3 biological replicates per genotype. Statistical analysis was performed by nonparametric Mann-Whitney test. **p < 0.01 and ****p < 0.0001 were considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B) Representative images of control and EC-Pik3caH1047R/WT mouse retinas  isolated at indicated  time points stained  with IB4  for blood vessels. Scale bars: 150 μm.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(A, B) Representative images of EC-Pik3caH1047R/WT (A) and EC-mTmG (B) P6 retinas from mice  treated with decreasing doses of 4-OHT on P1. Retinas  were stained  for  blood vessels  (IB4) and GFP  as indicated. Scale bars: 150 μm.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(D) Quantification of IB4-positive area per retina  in Pik3caH1047R/WT retinas. Data presented as a percentage of the control for each  4-OHT dose. Error bars are s.e.m. n = 4 retinas  per genotype. Data information: Statistical analysis was performed by nonparametric Mann-Whitney test. *p < 0.05 was considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(A) Representative images of EC-Pik3caH1047R/WT P6 retinas  isolated from mice  treated with 0.125 mg/kg of  4-OHT  on P1. Retinas  were immunostained  for blood vessels (IB4). Red asterisks show arteries  and arterioles  and yellow arrowheads veins. Scale bars: 150 μm (left panel) and 30 μm (right, high magnification panels). (B) Representative images of P6 retinas  from control and EC-Pik3caH1047R/WT mice  treated with 0.125 mg/kg 4-OHT on P1, following immunostaining  for p-S6  (S235/236) and blood vessels  (IB4). Scale bars: 150 μm (left panels) and 30 μm (right panels, high magnification). (C) Representative control and EC-Pik3caH1047R/WT P6 retinas immunostained  for blood vessels (IB4), EC nuclei  (Erg) and EdU. Scale bars: 150 μm (left panels) and 30 μm (right panels, high magnification). (D-G) Quantification of (D) p-S6  (S235/236) intensity (presented as a fold change of vehicle-treated control), (E) EC proliferation by EdU staining, (F) EC  number by Erg  positive cells and (G) retinal vascularity  by IB4-positive area in control and EC-Pik3caH1047R/WT retinas. Error bars are s.e.m. n > 5 retinas  per genotype. Statistical analysis was performed by nonparametric Mann-Whitney test. **p < 0.01 was considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B, C) Representative images of P6 retinas  isolated from control and EC-Pik3caH1047R/WT mouse  littermates. Blood vessels  were stained  with IB4. Lower panels showing high magnification images of the representative areas showing (B) blood vessels (IB4), EC nuclei  (Erg), EdU  incorporation and (C) pS6 (S235/236). Scale bars: 150 μm (upper panel) and 30 μm (lower panels). (D-G) Quantification of (D) retinal vascularity  by IB4 staining, (E) EC  number by Erg immunostaining, (F) EC proliferation  by EdU staining, and (G) pS6 (S235/236) intensity (presented as a fold change of vehicle-treated control). Bars represent the mean ± s.e.m. n ≥ 4 retinas  per genotype. Statistical analysis was performed by nonparametric Mann-Whitney test. *p < 0.05 and **p < 0.01 were considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B, C) Representative confocal  images of P6 retinas  isolated from control and EC-Pik3caH1047R/WT mouse  littermates. Blood vessels were stained  with IB4. Lower panels showing high magnification images of the representative areas showing (B) blood vessels (IB4), EC nuclei  (Erg), EdU  incorporation and (C) pS6 (S235/236). Scale bars: 150 μm (upper panels) and 30 μm (lower panels). (D-G) Quantification of (D) retinal vascularity  by IB4 staining, (E) EC  number by Erg immunostaining, (F) EC proliferation  by EdU staining, and (G) pS6 (S235/236) intensity (presented as a fold change of vehicle-treated control). Bars represent the mean ± s.e.m. n ≥ 3 retinas  per genotype. Statistical analysis was performed by nonparametric Mann-Whitney test. *p < 0.05 and **p < 0.01 were considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B, C) Representative confocal  images of P6 retinas  isolated from control and EC-Pik3caH1047R/WT mouse  littermates. Blood vessels were stained  with IB4. Lower panels showing high magnification images of the representative areas showing (B)  blood vessels (IB4), EC nuclei  (Erg), EdU  incorporation and (C) pS6 (S235/236). Scale bars: 150 μm (upper panels) and 30 μm (lower panels). (D-G) Quantification of (D) retinal vascularity  by IB4 staining, (E) EC  number by Erg immunostaining, (F) EC proliferation  by EdU staining, and (G) pS6 (S235/236) intensity (presented as a fold change of vehicle-treated control). Bars represent the mean ± s.e.m. n ≥ 4 retinas  per genotype. Statistical analysis was performed by nonparametric Mann-Whitney test. *p < 0.05, **p < 0.01 and ***p < 0.001 were considered statistically significant.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "(B) Representative sequencing chromatograms  of PIK3CA  and TEK  mutant VM-derived ECs. Arrows show the detected point mutations.",
    "ncbi_link": "PIK3CA: 5290
TEK: 7010"
  },
  {
    "caption": "(C) Representative confocal  images of PIK3CA  and TEK patient-derived ECs immunostained  for VE-cadherin (EC-specific junctional protein) and ERG  (EC-specific transcription factor). Cell nuclei  were visualised with DAPI. Scale bars: 30 μm.",
    "ncbi_link": "PIK3CA: 5290
TEK: 7010"
  },
  {
    "caption": "(D) Immunoblot  showing the activation of PI3K/AKT/mTORC1 pathway (by assessing the levels of p-AKT  and p-S6) among different PIK3CA  and TEK patient-derived ECs. Primary HUVEC  were used as wild-type control.",
    "ncbi_link": "PIK3CA: 5290
TEK: 7010"
  },
  {
    "caption": "(E-F) Immunoblot  showing the impact of miransertib  at increasing doses on PI3K/AKT/mTORC1  pathway (by assessing p-AKT  and p-S6 levels) in (E) PIK3CA  and (F) TEK  mutant patient-derived ECs.",
    "ncbi_link": "PIK3CA: 5290
TEK: 7010"
  },
  {
    "caption": "(G) Wild-type (HUVECs), PIK3CA  and TEK  mutant EC viability  upon the treatment with miransertib  for 72h at different doses assessed by MTS assay. Fitting curves and 95% CI IC50  values for wild-type (HUVECs), PIK3CA  and TEK ECs  are shown. For PIK3CA  and TEK-mutant ECs  n = 3 biological replicates (patients); for wild-type ECs  (HUVECs) n = 4 technical replicates PIK3CA-mutant vs. TEK-mutant p = 0.501; PIK3CA-mutant vs. HUVECs  p = 0.0815; TEK-mutant vs. HUVECs: p = 0.4085. Statistical analysis was performed by comparison of best-fit values using the extra sum-of-squares F test.",
    "ncbi_link": "PIK3CA: 5290
TEK: 7010"
  },
  {
    "caption": "(C) PCR analysis of a pool of transfected cells after treatment with Cas9-D10A 'nickase' and the indicated combination of gRNAs The ~200 bp product was centred around the start of exon 1 of the SLD5 gene. Efficient cutting of both template strands by Cas9-nickase was indicated by the production of a smeary PCR product (gRNAs 2+3), reflecting DNA repair that mostly produced small deletions around the nicking site The combination of gRNAs 1+3 did not produce a smeary PCR, due to a polymorphism within the PAM motif of the genomic locus",
    "ncbi_link": "Cas9: 57852564
SLD5: 109145"
  },
  {
    "caption": "(F) Immunoblot indicating successful tagging of both alleles of SLD5 with TAP or GFP.",
    "ncbi_link": "GFP: 
TAP: 
SLD5: 109145"
  },
  {
    "caption": "(D) The activity of CUL2LRR1 was inhibited in GFP-SLD5 cells , by treatment with a combination of LRR1 siRNA and MLN4924 Fixed cells were analysed Arrows indicate the accumulation of GFP-SLD5 on constitutive heterochromatin (49 % cells, n = 125). (E) Cells were treated as in (D) and the localisation of GFP-SLD5 was compared with CLASPIN by immunofluorescence. Arrows indicate the co-localisation of GFP-SLD5 and CLASPIN on constitutive heterochromatin (in 90 % cells with GFP-SLD5 patches, n = 103).",
    "ncbi_link": "LRR1: 69706"
  },
  {
    "caption": "(B) time-lapse analysis of mouse ES cells expressing GFP-SLD5 and mCherry-Histone H2B (from the CAG promoter at the ROSA26 locus after inhibition of CUL2LRR1. Arrows indicate heterochromatic patches of GFP-SLD5 that disappear during entry into mitosis (98 % cells, n = 97). (C) Equivalent data to (B) but for untreated cells (100 % of untreated cells lacked GFP-SLD5 on mitotic chromatin, n = 149).",
    "ncbi_link": "ROSA26: 14910"
  },
  {
    "caption": "(C) Immunoblot illustrating the stable expression from the CAG promoter of the indicated forms of TRAIP at the ROSA26 locus in TRAIP -/- mouse ES cells. Asterisks indicate non-specific bands. (D) Quantification of the percentage of mitotic cells with GFP-SLD5 on mitotic chromosomes, after inhibition of CUL2LRR1 in cells with the indicated genotypes. Cells were fixed before analysis.",
    "ncbi_link": "ROSA26: 14910
TRAIP: 22036"
  },
  {
    "caption": "F, G. AAV-mediated mutant HDAC3 (Y298H, V5) infection of DRG neurons induces neurite outgrowth (Tuj-1/V5 double positive neurons) after 36h in culture, which is repressed by wildtype HDAC3 overexpression. Scale bars, 100 μm. Data information: Data expressed as average neurite length ± s.e.m. N= 3-9 biological replicates. (*p<0.05, **p<0.01, ***p<0.005) indicate significant difference of 966 versus V5 vs AAV-GFP ANOVA followed by Bonferroni test).",
    "ncbi_link": "HDAC3: 15183"
  },
  {
    "caption": "A-E. PP4c gene silencing promotes HDAC3 phosphorylation in the presence of KCl (A-C, arrows), both in the nucleus and the cytoplasm (D). Scale bar, 20 μm. (C,D) Data is expressed as mean fold change vs scrambled (scr) siRNA of fluorescent intensity of pHDAC3 or PP4c in GFP positive cells ± s.e.m. N=3 biological replicates. (**p<0.01; ***p<0.005) indicate significant difference versus scrambled siRNA (Student's t-test). (E) PCR against PP4c demonstrates silencing of PP4c mRNA. F-G. PP2a gene silencing inhibits the KCl induced dephosphorylation of HDAC3 as shown by immunoblotting of pHDAC3 (F). (G) Data is expressed as mean fold change of immunoblot band intensity ± s.e.m. N= 3 biological replicates (*p<0.05; ****p<0.001) indicate significant difference versus control siRNA (Student's t-test). ",
    "ncbi_link": "PP2a: 19052
PP4c: 56420"
  },
  {
    "caption": "H-I. Genetic modification of activity-dependent phosphorylation of serine 424 of HDAC3 affects DRG neurite outgrowth. (H) DRG neurite outgrowth after transfection of control (V5 control), WT HDAC3-V5, phospho-dead HDAC3 (S424A)-V5 or phospho-mimetic HDAC3 (S424D)-V5 and after 24h in culture. Scale bar, 50µm. (I) Data is expressed as mean ± s.e.m. N= 8-9 biological replicates, approximately 35 V5 positive cells each. * p<0.05, ** p<0.01, *** p<0.005 indicate significant difference (One way ANOVA followed by Bonferroni).",
    "ncbi_link": "V5: 
HDAC3: 15183"
  },
  {
    "caption": "A-B. AAV-HDAC3 mutant (Y298H; dominant negative deacetylase inactive) promoted DRG regenerative growth after spinal cord injury vs AAV-V5 control (injected 5 weeks prior to SCI in the sciatic nerve bilaterally) as shown by dextran-red traced axons across and beyond the lesion site (GFAP, green) (dotted lines denote the rostral and caudal margins of the scar around the lesion). Scale bar, (A-B) 200 μm.",
    "ncbi_link": "V5: 
HDAC3: 15183"
  },
  {
    "caption": "C-F. Immunofluorescence for H3K9ac. AAV-HDAC3 mutant induced upregulation of H3K9ac in vivo in DRG neurons, but not in surrounding nuclei of satellite cells. Scale bar, (C-F) 50 μm.",
    "ncbi_link": "HDAC3: 15183"
  },
  {
    "caption": "G-J. New synaptic formations (VGlut1+) from regrowing axons are shown beyond the lesion site after injection of AAV-HDAC3mut. (G) Scale bar 200 μm, (H-J) High magnification insets depict co-localization of Dextran and vGlut1 staining. Scale bar 50 μm.",
    "ncbi_link": "HDAC3: 15183"
  },
  {
    "caption": "K-L. Quantification of dextran positive axons shows that AAV-HDAC3mut promotes DRG regenerative growth across and beyond the spinal lesion site. Data is expressed as percentage of dextran+ axons at each distance vs dextran+ axons at -700μm from the lesion margin (K) or distance from the caudal margin of the lesion to the most rostral dextran+ axon tip for each animal (L). N= 10 animals per condition, ± s.e.m. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001 indicate a significant difference (ANOVA followed by Bonferroni test).",
    "ncbi_link": "HDAC3: 15183"
  },
  {
    "caption": "A. Western blot of total pol II, Ser2P (Abcam or Cell Signaling), Ser5P (Abcam or Cell Signaling), and histone H3 as a loading control, on the chromatin fraction of CDK9as or wild-type HEK293 cells treated with DMSO or 15 µM 1-NA-PP1 for 15 or 30 minutes. B. Quantification of the western blots shown in A. n=2 biological replicates, except for Ser2P / pol II (Abcam) CDK9as NA 30 min, Ser5P / pol II (Abcam) CDK9as NA 15 min and NA 30 min, and Ser5P / pol II (Cell Signaling) CDK9as NA 30 min, where n=3 biological replicates.",
    "ncbi_link": "CDK9: 1025"
  },
  {
    "caption": "C. ChIP-qPCR of total pol II and of Ser2P (Abcam or Cell Signaling), and Ser5P (Abcam or Cell Signaling) ratioed to total pol II on KPNB1. n=3 biological replicates, mean ± SEM, p-value: * p < 0.05, ** p < 0.01, *** p < 0.001. Statistical test: two-tailed unpaired t test.",
    "ncbi_link": "KPNB1: 3837"
  },
  {
    "caption": "B. Western blot of total SF3B1, SF3B1 T142P, and histone H3 as a loading control, on the chromatin fraction of CDK9as cells treated for 30 minutes with DMSO, NA, tautomycetin (TT), calyculin A (CA), NA+TT, or NA+CA. The histone H3 loading control (CA samples) is the same as the loading control shown in Appendix Figure S3B as the same western blot experiment is shown in two different figures.",
    "ncbi_link": "CDK9: 1025"
  },
  {
    "caption": "C. Co-immunoprecipitation of CPSF2 in the CDK9as cell treated for 30 minutes with DMSO or NA followed by western blot with total pol II, CPSF2, CPSF3, SF3B1, SF3B3 and β-actin (negative control) antibodies.",
    "ncbi_link": "CDK9: 1025"
  },
  {
    "caption": "D. Co-immunoprecipitation of SF3B1 in the CDK9as cell treated for 30 minutes with DMSO, NA, or DRB followed by western blot with total pol II, SF3B1, SF3B2, and GAPDH (negative control) antibodies.",
    "ncbi_link": "CDK9: 1025"
  },
  {
    "caption": "D. ChIP-qPCR of Ser2P, CPSF73, or CPSF2 ratioed to total pol II after 30 minutes treatment with DMSO, DRB, CA, or DRB+CA on KPNB1.",
    "ncbi_link": "KPNB1: 3837"
  },
  {
    "caption": "a, Immunoprecipitation of Flag-beclin 1 constructs with Nef-HA in HeLa cells 24 h post-transfection.",
    "ncbi_link": "Nef: 156110"
  },
  {
    "caption": "b, GFP-LC3-positive dots (autophagosomes) in MCF7 cells expressing GFP-LC3 and Flag-beclin 1 constructs grown in either normal medium or starved in EBSS for 2 h.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "a, HeLa cells were treated with biotin-conjugated peptides (30 μM, 3 h) and proteins bound to peptides were analysed by immunoblot with anti-GAPR-1. b-T-B, biotin-Tat-beclin 1; b-T-S, biotin-Tat-scrambled.",
    "ncbi_link": "Tat: 
beclin 1: 8678"
  },
  {
    "caption": "b, Immunoprecipitation of Flag-beclin 1 with GAPR-1-Myc in HeLa cells 24 h post-transfection.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "a, Percentage of cells with small htt103Q aggregates (left) and number of aggregates per cell (right) in HeLa cells expressing doxycycline (Dox)-repressible CFP-htt103Q after daily treatment with doxycycline or peptide (20 μM, 4 h per day) for 2 days. Bars represent mean ± s.e.m. of triplicate samples (60-120 cells per sample). Similar results were observed in three independent experiments.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "f, HIV-1p24 antigen release in MDMs transduced with nonspecific scrambled shRNA (shNS) or ATG5 shRNA (shATG5) and treated daily with peptide (5 µM). Values represent mean ± s.e.m. of triplicate wells. Similar results were observed in MDMs from two independent donors.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "b, p62 immunoblot of brains of 5-day-old GFP-LC3 mice treated with the indicated peptide (20 mg kg−1 i.p., 6 h).",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "d-f, Representative images of WNV envelope antigen and TdT-mediated dUTP nick end labelling (TUNEL) staining (d) (T, Tat alone), quantification of cell death in brain (e) and survival curves (f) for 5-day-oldC57BL/6Jmice infected with WNV (Egypt strain 101, 1 p.f.u. intracerebral (i.c.)) and treated daily with peptide (D-amino acid forms, 20mgkg−1 i.p. beginning 1day post-infection). Images in d are from cerebral cortex day 6 post-infection. Similar results were observed in all regions of the brain for three mice per group. Scale bar, 20μm. Bars in e represent mean±s.e.m. TUNEL-positive cells per unit area of brain for three mice. g",
    "ncbi_link": "Tat: "
  },
  {
    "caption": "(f) Endogenous USP33 interacts with RALB. Flag-RALB was immunoprecipitated using anti-Flag (M2) agarose and analysed for co-precipitation with endogenous USP33 using anti-USP33 antibody. Cells expressing USP33 shRNA were used as a negative control.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(h) USP33 affects ubiquitylation of RALB, but not RALA. 6xHis-tagged ubiquitin and Flag-RAL-G23V mutants were introduced into HEK293T cells stably expressing GFP shRNA or USP33 shRNA. Ubiquitylated RAL proteins were purified by Co2+ metal affinity chromatography and detected by antibodies specific to RALA or RALB. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(d) USP33 regulates RALB ubiquitylation at Lys 47. (e) The GTP-GDP status of RALB affects RALB ubiquitylation at Lys 47. For c-e, 6xHis-tagged ubiquitin and the indicated RALB mutants were introduced into HEK293T cells expressing GFP shRNA or USP33 shRNA. Ubiquitylated RALB was purified by Co2+ metal affinity chromatography and detected by antibodies specific to RALB. WT, wild type.",
    "ncbi_link": "RALB: 5899
USP33: 23032"
  },
  {
    "caption": "(f) Lack of ubiquitylation at Lys 47 inhibits RALB binding to SEC5. The indicated Flag-tagged RALB mutants were overexpressed in HEK293T cells and then immunoprecipitated with anti-Flag (M2) agarose followed by immunoblotting using anti-SEC5 antibody.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "g) Ubiquitylation at Lys 47 impairs RALB binding to EXO84. Flag-tagged RALB mutants were overexpressed in HEK293T cells and then immunoprecipitated with anti-Flag (M2) agarose followed by immunoblotting using anti-EXO84 antibody.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(h) Ubiquitylation at Lys 47 does not affect RALB activity. The activity of RALB mutants was determined by a RALBP1-RBD binding assay.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(a) USP33 does not affect RALB activity. The activity of RALB was determined in HEK293T cells expressing GFP shRNA or USP33 shRNA and empty vector (V) or HA-tagged USP33 by RALBP1-RBD binding assay.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(b) USP33 modulates interaction between RALB and SEC5. Flag-tagged RALB was overexpressed in HEK293T cells expressing GFP shRNA, USP33 shRNA, empty vector (V) or HA-tagged USP33. The indicated proteins were then immunoprecipitated with anti-Flag (M2) agarose followed by immunoblotting using anti-Flag or anti-SEC5 antibodies.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(e) RALB ubiquitylation controls interaction between EXO84 and SEC5. Flag-tagged SEC5 was immunoprecipitated using anti-Flag (M2) agarose from HEK293T cells overexpressing RALB-G23V or RALB-G23V-K47R. The presence of EXO84 in SEC5 complexes was analysed by immunoblotting using anti-EXO84 antibody.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(f) USP33 regulates EXO84-SEC5 complex formation. Flag-tagged SEC5 was immunoprecipitated using anti-Flag (M2) agarose from HEK293T cells expressing the indicated constructs followed by immunoblotting using anti-EXO84 antibody.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(g) Suppression of SEC5 affects RALB binding to EXO84. HA-tagged RALB-G23V was immunoprecipitated from HEK293T cells expressing the indicated constructs. The presence of EXO84 in RALB complexes was analysed by immunoblotting using anti-EXO84 antibody. For a-c,f,g immunoblotting using antibodies specific for USP33, anti-Flag (M2) or anti-HA determined the levels of USP33 suppression or overexpression. Immunoblot analysis was performed using the indicated antibodies. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "SEC5: 55770"
  },
  {
    "caption": "(a) Suppression of USP33 facilitates TBK1-SEC5 complex formation. Flag-tagged SEC5 was introduced into HEK293T cells expressing empty vector (V) or HA-tagged RALB-G23V together with GFP shRNA or USP33 shRNA as indicated, and then immunoprecipitated with anti-Flag (M2) agarose followed by immunoblotting using antibody specific for TBK1.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(c) RALB ubiquitylation at Lys 47 is crucial for formation of the RALB-SEC5 complex in response to poly(I:C) treatment. Flag-tagged SEC5 and the indicated HA-tagged RALB mutants were introduced into 293-hTLR3 cells. At 48 h after transfection cells were treated 100 μg ml−1 of poly(I:C) for 6 h. Flag-tagged SEC5 was immunoprecipitated with anti-Flag (M2), and analysed for co-precipitation by immunoblotting using anti-HA antibody.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(d) RALB ubiquitylation at Lys 47 affects activation of TBK1 and IRF3. At 48 h after transfection with empty vector (V), Flag-RALB-G23V and Flag-RALB-G23V-K47R, 293-hTLR3 cells were treated with 10 μg ml−1 of poly(I:C) for 6 h. Immunoblot analysis was performed using the indicated antibodies. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(a-d) USP33 inhibits assembly of SEC5-beclin-1 complexes. The indicated proteins were immunoprecipitated from cells expressing GFP shRNA or USP33 shRNA with anti-Flag (M2), anti-HA or anti-SEC5 antibody and analysed for co-precipitation by immunoblotting using specific antibodies as indicated.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(e) USP33 potentiates the interaction between EXO84 and beclin 1. Endogenous beclin 1 was immunoprecipitated from HEK293T cells, expressing either empty vector (V), HA-USP33 wild type (WT) or the catalytically inactive mutant C194S-H683Q, using anti-beclin 1 antibody. Immunoprecipitates were analysed for co-precipitation by immunoblotting using anti-EXO84 or anti-beclin 1 antibodies.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(f,g) RALB but not RALA undergoes deubiquitylation under nutrient deprivation. 6xHis-tagged ubiquitin and the indicated RAL mutants were overexpressed in HEK293T cells. At 48 h after transfection cells were deprived of nutrients and incubated in Hank's buffered salt solution (HBSS) medium for 90 min. Ubiquitylated RALproteins were purified by Co2+ metal affinity chromatography and analysed by immunoblotting using anti-RALA or anti-RALB antibodies.",
    "ncbi_link": "RALB: 5899"
  },
  {
    "caption": "(a) USP33 depletion inhibits accumulation of LC3-lipid conjugates. HEK TE cells stably expressing GFP shRNA or USP33 shRNA were incubated with DMEM or HBSS medium for 4 h, in the presence or absence of 50 μM of chloroquine (CQ). Cells were then assayed for the relative accumulation of LC3-I and LC3-II by immunoblotting analysis using anti-LC3 antibody. LC3-II/GAPDH ratios have been calculated using ImageJ densitometric analysis.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(b-d) USP33 expression levels affect the accumulation of LC3punctae. Wild-type USP33 or a USP33-shRNA-resistant USP33 mutant (USP33R) was introduced into HEK TE cells stably expressing GFP shRNA or USP33 shRNA. The generated cells were incubated in HBSS medium for 4 h. USP33 was analysed by immunoblotting using anti-USP33 antibody (b). Representative images of LC3immunostaining are shown (c). Endogenous LC3punctae were quantified using the In Cell Analyser 2000 automatic imaging system and IN Cell Investigator software. The mean distribution of LC3punctae per cell is represented as the mean of two independent experiments. Statistics source data for d can be found in Supplementary Table S1 (d).",
    "ncbi_link": "USP33: 23032
USP33R: 23032"
  },
  {
    "caption": "(e) USP33 depletion leads to increased levels of p62. HEK TE cells expressing GFP shRNA or USP33 shRNA were incubated in HBSS medium for the indicated periods of time. Immunoblotting was performed using the indicated antibodies.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(f) Overexpression of the RALB-G23V-K47R mutant leads to accumulation of LC3-lipid conjugates. HEK293T cells overexpressing the RALB-G23V or RALB-G23V-K47R mutants were assayed for the relative accumulation of LC3-I and LC3-II by immunoblotting using anti-LC3 antibody.",
    "ncbi_link": "G23V: 5899
K47R: 5899
RALB: 5899"
  },
  {
    "caption": "(a) Fluorescence microscopy of GFP-LC3-transduced HeLa cells left unstimulated (Unstim) or stimulated for 4 h with C12-iEDAP (2.5 μg/ml) or for 2 h with rapamycin (Rapa; 50 μg/ml). Green, GFP-LC3; blue, DAPI (DNA-intercalating dye). Scale bar, 5 μm. (b) Quantification of dot- or ring-shaped GFP-LC3 signals (representing autophagosomes) in HeLa cells stimulated as described in a.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(c) Confocal microscopy of wild-type and Nod2-deficient BMDMs transduced with GFP-LC3 (green) and left unstimulated or stimulated for 4 h with LPS (1 μg/ml) or MDP (100 μg/ml) or for 2 h with rapamycin (50 μg/ml). Scale bar, 15 μm. (d) Quantification of dot- or ring-shaped GFP-LC3 (green) in BMDMs stimulated as described in c.",
    "ncbi_link": "LC3: 67443///66734
Nod2: 257632"
  },
  {
    "caption": "(e) Immunofluorescence microscopy of macrophages recovered from the peritoneal cavities of thioglycolate-injected wild-type, Nod1- and Nod2-deficient mice 4 h after intraperitoneal injection of MDP (300 μg/ml), FK565 (300 μg/ml) or rapamycin (300 μg/ml); after centrifugation by cytospin, cells were stained for endogenous LC3 (red) and with DAPI (blue). Scale bar, 10 μm. (f) Quantification of dot- or ring-shaped LC3 signals in macrophages recovered from the peritoneal cavities of mice treated as described in c. Data are representative of four (a-d) or two (e,f) independent experiments with at least 100 cells per condition (error bars (b,d,f), s.d.).",
    "ncbi_link": "Nod1: 107607
Nod2: 257632"
  },
  {
    "caption": "(a) Confocal microscopy of wild-type and Nod1-deficient GFP-LC3-expressing MEFs infected for 2 h with wild-type S. flexneri M90T-RFP. (b) Quantification of the colocalization of GFP-LC3 signals with bacteria in a.",
    "ncbi_link": "LC3: 67443///66734
Nod1: 107607"
  },
  {
    "caption": "(c) Confocal microscopy of wild-type and Nod1-deficient GFP-LC3-expressing MEFs infected for 2 h with S. flexneri ΔIcsB-RFP. (d) Quantification of the colocalization of GFP-LC3 signals with bacteria in c.",
    "ncbi_link": "IcsB: 20467568
LC3: 67443///66734
Nod1: 107607"
  },
  {
    "caption": "(e,f) Plate assay of bacteria in wild-type or Nod1-deficient MEFs infected for 0.5 h with S. flexneri ΔIcsB in the presence or absence of the autophagy blocker LY294002 (LY) or protease inhibitors (PI), followed by 5.5 h of incubation in the presence of gentamicin.",
    "ncbi_link": "IcsB: 20467568
Nod1: 107607"
  },
  {
    "caption": "(g-j) Confocal microscopy (g,i) and quantification of the colocalization of GFP-LC3 signals with M90T and ΔIcsB (h,j) in wild-type and RIP2-deficient (Ripk2−/−) GFP-LC3-expressing MEFs infected for 2 h with wild-type S. flexneri (M90T; g,h) or ΔIcsB S. flexneri (i,j).",
    "ncbi_link": "IcsB: 20467568
LC3: 67443///66734
RIP2: 192656
Ripk2: 192656"
  },
  {
    "caption": "(k) Enzyme-linked immunosorbent assay of KC secretion by wild-type and RIP2-deficient MEFs infected for 0.5 h with M90T and incubated for 5.5 h in the presence of gentamicin.",
    "ncbi_link": "RIP2: 192656"
  },
  {
    "caption": "(l,m) Confocal microscopy (l) and quantification of the colocalization of GFP-LC3 signals (green) with M90T and ΔIcsB (m) of wild-type and NEMO-deficient (Ikbkg−/−) GFP-LC3-expressing MEFs infected for 0.5 h with wild-type S. flexneri (M90T) or S. flexneri ΔIcsB and incubated for 1.5 h in the presence of gentamicin. Red, RFP. Arrows indicate colocalization of GFP-LC3 signals with S. flexneri. Scale bars, 10 μm. *P 0.05, and **P 0.01 (t-test). Data represent three independent experiments with at least 100 cells each (error bars, s.e.m.).",
    "ncbi_link": "IcsB: 20467568
Ikbkg: 16151
NEMO: 16151
LC3: 67443///66734"
  },
  {
    "caption": "(a) Immunofluorescence of HeLa cells expressing hemagglutinin-tagged Nod1 (HA-Nod1 (red); top) or HA-Nod2 (red; bottom). Blue, DAPI.",
    "ncbi_link": "Nod1: 10392
Nod2: 64127"
  },
  {
    "caption": "(b) Immunofluorescence of HeLa cells expressing Myc-tagged FL-ATG16L1 (Myc-FL-ATG16L1).",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(c,d) Immunofluorescence of HeLa cells coexpressing HA-Nod1 (red; c) or HA-Nod2 (red; d) and Myc-FL-ATG16L1 (green). Blue, DAPI.",
    "ncbi_link": "ATG16L1: 55054
Nod1: 10392
Nod2: 64127"
  },
  {
    "caption": "(e) Immunofluorescence of HeLa cells expressing a Flag-tagged truncated form of ATG16L1 (Flag-ΔN85-ATG16L1; green). Blue, DAPI.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(f) Immunofluorescence of HeLa cells coexpressing HA-Nod2 (red) and Flag-ΔN85-ATG16L1 (green). Blue, DAPI.",
    "ncbi_link": "ATG16L1: 55054
Nod2: 64127"
  },
  {
    "caption": "(h,i) Immunoprecipitation (IP) and immunoblot (IB) analysis of HEK293 cells transfected with Flag-ΔN85-ATG16L1 (h) or Myc-FL-ATG16L1 (i), together with HA-Nod1, HA-Nod2 or HA-tagged enhanced GFP (EGFP-HA). Ig, immunoglobulin (loading control). Results are representative of one of at least three independent experiments (a-g) or one of three independent experiments (h,i).",
    "ncbi_link": "ATG16L1: 55054
Nod1: 10392
Nod2: 64127"
  },
  {
    "caption": "Immunofluorescence microscopy of wild-type and RIP2-deficient MEFs expressing Flag-tagged ΔN85-ATG16L1 and HA-Nod1 (a) or HA-Nod2 (b). Scale bars, 10 μm. Area outlined at far left is enlarged at right. Data are representative one of two independent experiments.",
    "ncbi_link": "ATG16L1: 77040
Nod1: 107607
Nod2: 257632
RIP2: 192656"
  },
  {
    "caption": "(a) Fluorescence microscopy of immortalized GFP-LC3-transduced lymphoblasts from donors homozygous for the normal ATG16L1*300T allele (300T) or risk allele ATG16L1*300A (300A), left unstimulated or treated for 2 h with rapamycin (50 μg/ml) or for 4 h with MDP (20 μg/ml). Green, GFP-LC3. Scale bar, 5 μm. (b) Induction of GFP-LC3 signals by rapamycin, MDP or Gram-positive peptidoglycan (PG+; 20 μg/ml) in cells treated as described in a, presented relative to GFP-LC3 signals in unstimulated control cells. *P 0.05 (t-test). Data represent three independent experiments (error bars (b), s.d.).",
    "ncbi_link": "ATG16L1: 55054
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) Immunofluorescence microscopy of HeLa cells transfected with HA-Nod2 (red) and Flag-ΔN85-ATG16L1(green) and infected for 10-20 min with S. flexneri M90T. Blue, DAPI. Arrows indicate colocalization of Nod2 and ATG16L1 around invading bacteria. Scale bars, 5 μm. Data are representative of one of three independent experiments.",
    "ncbi_link": "ATG16L1: 55054
Nod2: 64127"
  },
  {
    "caption": "(a,b) Immunofluorescence microscopy of HeLa cells expressing Flag-ΔN85-ATG16L1 (green; a) or Myc-FL-ATG16L1 (green; b) and HA-tagged Nod2 L1007fsinsC (HA-Nod2, 1007fs). Area outlined at left is enlarged in other images.",
    "ncbi_link": "ATG16L1: 55054
Nod2: 64127"
  },
  {
    "caption": "(c,d) Immunofluorescence microscopy of HeLa cells expressing Flag-ΔN85-ATG16L1 (c) or Myc-FL-ATG16L1 (d) together with HA-tagged Nod2fs (red). Blue, DAPI. Scale bar, 8 μm.",
    "ncbi_link": "ATG16L1: 55054
Nod2: 64127"
  },
  {
    "caption": "(c,d) Immunofluorescence microscopy of HeLa cells expressing Flag-ΔN85-ATG16L1 (c) or Myc-FL-ATG16L1 (d) together with HA-tagged Nod2fs (red). Blue, DAPI. Scale bar, 8 μm.",
    "ncbi_link": "ATG16L1: 55054
Nod2: 64127"
  },
  {
    "caption": "(e) Immunofluorescence microscopy of wild-type and Nod2fs-KI BMDMs transduced with GFP-LC3 (green) and infected for 0.5 h with S. flexneri M90T-RFP (red), followed by incubation for 1 h with gentamicin. Arrows indicate no colocalization of Nod2 with ΔN85-ATG16L1 or FL-ATG16L1. Scale bar, 15 μm. (f) Quantification of the colocalization of GFP-LC3 signals with S. flexneri M90T-RFP in experiments as described in e. Data are representative of one of three independent experiments (error bars (f), s.d.).",
    "ncbi_link": "ATG16L1: 77040
LC3: 67443///66734
Nod2: 257632"
  },
  {
    "caption": "(A) HEK293 cells stably expressing GFP-LC3 were transfected with control (upper) or Atg-5 siRNA (lower). After 36 h, α-synuclein fibrils were introduced into them for 4 h, followed by immunostaining with anti-phospho-α-synuclein antibody (P-αSyn). Blue, DAPI. Scale bar, 10 µm.",
    "ncbi_link": "Atg-5: 9474"
  },
  {
    "caption": "(C) Clearance of α-synuclein inclusions in control (solid bar) or Atg-5 (open bar) knockdown cells was measured at 4 h and 24 h after α-synuclein fibrils. The number of phosphorylated α-synuclein-positive cells was assessed in randomly chosen fields (n = 5). Data from each experiment are were normalized to Cont-siRNA-4 h (100%) and represented as relative value of α-synuclein inclusions ± s.e.m. Statistical analysis was performed with one-way ANOVA (post-hoc Tukey's test). *p<0.01",
    "ncbi_link": "Atg-5: 9474"
  },
  {
    "caption": "(A) HEK293 cells stably expressing GFP-LC3 were transfected with p62-siRNA (right panels) or control-siRNA (left panels). Phosphorylated α-synuclein-positive inclusions (P-αSyn) are indicated by arrowheads. In p62-knockdown cells, the expression and accumulation of p62 were not detected, and inclusions were never sequestrated by GFP-LC3 autophagosomes. Scale bars, 20 µm.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(C) α-Synuclein fibrils were introduced into control (Cont) or p62-knockdown (p62) cells. Four hours after introduction, cell lysates were subjected to immunoblotting analysis using anti-LC3 (upper panel) or anti-actin (lower panel) antibodies. Quantification of the relative levels of LC3-II/Actin is shown with the ratio. Relative level of LC3-II/Actin was represented by mean ± s.d. as a graph. Statistical analysis was performed with one-way ANOVA (post-hoc Tukey's test). *p<0.01. This experiment was repeated three times.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(D) Clearance of α-synuclein inclusions in control (solid bar) or p62 (open bar) knockdown cells was measured at 4 h and 24 h after α-synuclein fibrils. The number of phosphorylated α-synuclein-positive cells was assessed in randomly chosen fields (n = 5). Data from each experiment were normalized to Cont-siRNA-4 h (100%) and represented as relative value of α-synuclein inclusions ± s.e.m. Statistical analysis was performed with one-way ANOVA (post-hoc Tukey's test). *p<0.01.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(A-C) qRT-PCR measurement of Ifnb1 transcripts in mouse peritoneal macrophages (A), THP1 cells (B) and human peripheral blood mononuclear cells  (PBMC) (C) that were left unstimulated or stimulated with 2'3' cGAMP  (0.1μg/mL) for 4 h in the presence of DMSO or indicated concentrations of Palbociclib (0.1, 1, 10 μM). The data are presented as fold induction of Ifnb1/Gapdh transcripts. The data shown are mean±SEM of n=3 biological replicates. Statistical significance was determined by one-way ANOVA followed by Dunnett's post hoc test. *, P<0.05; ****, P<0.0001.",
    "ncbi_link": "Gapdh: 
Ifnb1: 15977
Ifnb1: 3456"
  },
  {
    "caption": "(G-H)  qRT-PCR measurement of Il1b (G) and Il6 (H) transcripts in mouse peritoneal macrophages left unstimulated or stimulated with 2'3' cGAMP (0.1 μg/mL) in the presence of DMSO or Palbociclib (10 μM) for indicated times. The data shown are mean ± SEM of n=3 biological replicates. Statistical significance was determined by two-way ANOVA followed by Tukey's post hoc test. *, P<0.05; ****, P<0.0001 ; ns, not significant. (I-J) qRT-PCR  measurement of Il1b (I) and Il6 (J) transcripts in THP1 cells left unstimulated or stimulated with 2'3' cGAMP  (0.1μg/mL) in the presence of DMSO or Palbociclib (10 μM) for indicated times. The data shown are mean ± SEM of n=3 biological replicates. Statistical significance was determined by two-way ANOVA followed by Tukey's post hoc test. *, P<0.05; ****, P<0.0001 ; ns, not significant.",
    "ncbi_link": "Il1b: 16176
Il1b: 3553
Il6: 16193
Il6: 3569"
  },
  {
    "caption": "Immunoblotting of the streptavidin precipitates of the mixture of biotin (100 μM) or biotin-Palbociclib (100 μM) and the lysates of HEK293T cells transfected with Flag-STING (C) The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
STING: 340061"
  },
  {
    "caption": "(G) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with Flag-STING and HA-STING in the presence of DMSO and indicated concentrations of Palbociclib. The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STING: 340061"
  },
  {
    "caption": "(J) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with Flag-STEEP and HA-STING in the presence of DMSO or Palbociclib (10 μM). The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STEEP: 63932
STING: 340061"
  },
  {
    "caption": "(K) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with Flag-STING and HA-TBK1 in the presence of DMSO or indicated concentrations of Palbociclib. The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STING: 340061
TBK1: 29110"
  },
  {
    "caption": "(C) Immunoblotting of the streptavidin precipitates of the mixture of biotin-Palbociclib (100 μM) and the lysates of HEK293T cells transfected with corresponding Flag-STING  mutants. The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
STING: 340061"
  },
  {
    "caption": "(D) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with HA-STING and Flag-STING or Flag-STING Y167A in the presence of DMSO and Palbociclib (10 μM). The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STING: 340061"
  },
  {
    "caption": "(G) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with HA-TBK1 and Flag-STING or Flag-STING Y167A. The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STING: 340061
TBK1: 29110"
  },
  {
    "caption": "(H) Immunoblotting of the lysates and anti-Flag immunoprecipitates of HEK293T cells transfected with HA-STING and Flag-STING C91A in the presence of DMSO and Palbociclib (10 μM). The data shown are representative of n=3 biological replicates.",
    "ncbi_link": "Flag: 
HA: 
STING: 340061"
  },
  {
    "caption": "(G-I)  qRT-PCR measurement of transcripts of Ifnb1 (G), Il6 (H) and Il1b (I) in mouse colon tissues harvested from mice of indicated groups. The data shown are mean ± SEM of n=5 mice from 1 of 3 biological replicates with similar results. Each symbol indicates the value of 1 mouse from n = 5 mice per group. Statistical significance was determined by one-way ANOVA test followed by Tukey's multiple comparisons post-hoc test between all groups. *, P<0.05; **, P<0.01; ****, P<0.0001; ns, not significant.",
    "ncbi_link": "Ifnb1: 15977
Il1b: 16176
Il6: 16193"
  },
  {
    "caption": "(G-I) qRT-PCR measurement of transcripts of Ifnb1(G), Cxcl10 (H) and Il6 (I) in mouse stomach tissues harvested from mice of indicated groups. The data shown are mean ± SEM of n=5 mice from 1 of 3 biological replicates with similar results. Each symbol indicates the value of 1 mouse from n = 5 mice per group. Statistical significance was determined by one-way ANOVA test followed by Tukey's multiple comparisons post-hoc test between all groups. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001; ns, not significant.",
    "ncbi_link": "Cxcl10: 15945
Ifnb1: 15977
Il6: 16193"
  },
  {
    "caption": "E Western blot analysis of PLPs transfected with control or ATG3 siRNA, with or without treatment of 1 mM H2O2. Each lane displayed a different transfected group.F Quantification analysis of ATG3, phosphorylated p53 (ser15), p53, and GAPDH in each group. (ATG3 in ATG3 siRNA; **p=0.0003 vs control group, pp53 in ATG3 siRNA/ H2O2; *p=0.0145 vs. H2O2 group).",
    "ncbi_link": "ATG3: 64422"
  },
  {
    "caption": "G Representative western blot analysis of phosphorylated p53, and Parkin in Parkin -/- mice compared to WT. Quantification analysis of phosphorylated p53 and Parkin (Parkin; **p=0.0001 vs. WT, pp53; *p=0.019 vs. WT, n=4).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "H ΔΨm and platelet apoptosis were measured by flow cytometry analysis in WT or WT_H2O2 and Parkin -/- or Parkin -/-_H2O2 mouse platelets. ΔΨm was detected using TMRM (WT_ H2O2; **p= 0.002 vs. WT group, Parkin-/-_ H2O2; **p= 1.61525E-06 vs. Parkin-/- group, n=3)I Apoptosis level was assessed with Annexin-V (PS externalization). Graph indicates the percentage of Annexin V positive cell in total cell population (Parkin-/- : *p=0.010 vs. WT group, Parkin-/-_ H2O2 ;**p= 0.008 vs. WT_ H2O2; group, Parkin-/-_ H2O2; **p=0.001 vs. Parkin-/- group, NS means no significance n=3)",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "J Western blot analysis in WT and Parkin -/- demonstrating the inability to induce LC3 despite the addition of H2O2. Shown graphically are the LC3II to LC3I ratios (WT_ H2O2;*p=0.028 vs. WT group, n=3)",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "A Representative western blot analysis of pp53 in WT (n=6), DM (n=6) and PINK1-/-DM mice (n=3). GAPDH served as the loading control (DM ; **p=0.006 vs. WT group, PINK1-/-DM; **p=0.004 vs. DM group).",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "B Measurement of p-selectin translocation to the cell membrane by flow cytometry analysis in WT (n=3), DM (n=3) and PINK1 -/- DM (n=3) miceplatelets. Graphs indicate mean fluorescence intensity (MFI) in each group. (*p<0.05 vs. WT or DM).",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "C Quantification of vessel occlusion time after carotid arterial flow measurement (WT and DM; and PINK1 -/- : **p<0.01 vs. WT or DM).",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "D Plot of carotid arterial flow by Doppler flow probe after 2 min FeCl3 injury, indicative of occlusive thrombosis. Flow was plotted as percentage of baseline flow before injury (DM: n=3, PINK1-/- DM; n=3).",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(M) average duration in movement in an open field as a function of time after treating  Gbeys/ys mice with vehicle (n=8) or 144DG11 (n=9) at 6 months of age (at onset). Data information: Two way ANOVA with repeated measures show that, throughout the period, treatment values were not different than vehicle (p<0.15).",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "(A) Left panel, Mice, treated as indicated, were sacrificed and the indicated tissues were collected and stained for PG (arrows) with  PAS following diastase treatment. Scale bars, 200 µm (liver, muscle), 50 µm (cortex, heart, peripheral nerve). Right panel, PAS staining  was quantified based on analysis of 4 sections from each tissue in n=3 wt, n=7 Gbeys/ys vehicle-treated, and n=9 144DG11-treated mice.",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "(C) 144DG11  Pharmacokinetics. Gbeys/ys mice injected with 144DG1 were sacrificed 30, 60, 90, and 210 min post injection and the indicated tissues were removed, as well as 200 uL of serum drawn. Graph shows means (+/- SEM) of 144DG11 levels in the different tissues determined by  LC-MS/MS Results obtained from n = 3 mice at each  time point.",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "A-F Mice were monitored over a 24 hr period. Effective  mass was calculated by ANCOVA Data are mean±SEM from nine month old mice  (n=11, wt vehicle-treated, n=6 Gbeys/ys vehicle-treated, and n=7 Gbeys/ys 144DG11-treated). Vehicle-treated Gbeys/ys mice  demonstrate lower respiratory quotient (in the  light) (A), total energy expenditure (TEE) (B), and  fat oxidation (C) compared to wt controls. 144DG11  treatment increased these parameters (for fat oxidation only in the dark  and total time). Carbohydrate oxidation and ambulatory activity, not significantly affected by the diseased state, were increased by  144DG11 even beyond wt control levels (D and E) (note, while 144DG11 increased carbohydrate oxidation in the light (D), p was only <0.06). 144DG11 also reversed the decrease in meal size and water  sip volume observed in Gbeys/ys mice as compared to wt control (F). Data information: *p<0.05 v wt controls, #p<0.05 v Gbeys/ys vehicle treated mice. Statistical differences were determined by two-tailed t-tests.",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "(G) Blood metabolic panel based on n=3, 9.5 month old mice treated as indicated. Blood glucose was increased and blood triglycerides decreased in Gbeys/ys cells by 144DG11 (p<0.05).",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "(B) Left panel, TEM images of liver tissue from vehicle or  144DG11-treated Gbeys/ys mice. High-magnification (right, scale bars=200 nm) and low-magnification (left, scale bars=1 µm) images show higher levels of  glycogen/polyglucosan in  lysosomes and cytosol, respectively. Right panel, quantification (+/- s.d) of lysosomal glycogen particles (n=3 biological replicates, *p<0.03, two-tailed t-test). G, Glycogen/polyglucosan; L, Lysosomes; M, Mitochondria.",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "(E)  LAMP1-KD and 144DG11 treatment cause  lysosomal acidification. Upper panel, flow cytometry results showing that 144DG11 slightly increased acidification (yellow to blue median fluorescence ratio (Y/B)) in control, GFP-transduced, APBD fibroblasts (Y/B(GFP/144DG11)>Y/B(GFP), p<0.12), but significantly acidified  LAMP1-KD, GFP-shLAMP1-transduced, APBD fibroblasts (Y/B(LAMP1-KD/144DG11)>(Y/B(LAMP1-KD), p<0.03). LAMP1-KD itself led to the most significant acidification (Y/B (LAMP1-KD)>Y/B(GFP), p<0.007). n=3, two-tailed t-tests. Middle panel Lysosensor staining of the corresponding cells. Yellow fluorescence intensity correlates with acidification. Lower panel, PAS  (glycogen)  staining  of the corresponding cells. Scale bars, 50 µm.",
    "ncbi_link": "GFP: 
LAMP1: 16783"
  },
  {
    "caption": "(G) 144DG11  reduces  lysosomal  (LAMP1 positive) area in liver, but not muscle, of Gbeys/ys mice  (n=3 biological replicates, *p<0.01, two-tailed t-test , SEM).Scale bars, 5 µm for liver (upper left panel), and 10 µm for muscle (lower left panel). Right panel shows quantification of the left panel.",
    "ncbi_link": "Gbe: 74185"
  },
  {
    "caption": "B. NIH3T3 cells transfected with KV10.1 (red bars) showed markedly less cilia than control cells (empty vector, white bars). Subconfluent cultures grown in the presence of FCS were serum starved for 24 hours to induce ciliogenesis. Cilia were stained with anti acetylated α-tubulin antibody. To determine ciliary disassembly, cells were starved for 24 hours and then incubated for 4h in FCS to induce cell cycle re-entry and ciliary resorption.",
    "ncbi_link": "KV10.1: 16510"
  },
  {
    "caption": "C. Similarly, hTERT-RPE1 cells transfected with KV10.1 also showed less cilia. Ciliogenesis and ciliary disassembly were induced as in B and cilia were stained using anti acetylated α-tubulin and quantified as in A. The Inset shows the equivalent experiment using the structurally related potassium channel KV10.2, which did not alter the frequency of expression of cilia.D. Examples of fields of view of hTERT-RPE1 cells transfected with KV10.1, serum starved for 24 hours and cilia were revealed with anti Arl13B antibody (arrows). A majority of control-transfected cells showed cilia, while KV10.1 transfected did not. Scale bar: 10µm.",
    "ncbi_link": "KV10.1: 3756
KV10.2: 27133"
  },
  {
    "caption": "A. Representative images showing hTERT-RPE1 grown in the presence of serum and stained with anti acetylated α-tubulin antibody. There were more ciliated cells after treatment with siRNA against KV10.1 (KV10.1 KD), as compared to scrambled siRNA-transfected cells, which were devoid of cilia (control). Scale bar: 10 µm.B. Quantification of the effect depicted in A for the number of images indicated at the base of the columns.",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "C. Time course of ciliary disassembly. hTERT-RPE1 cells were serum starved for 24 hours, fixed at the times indicated after serum reintroduction, and stained with anti acetylated α-tubulin to reveal cilia. While in the presence of scrambled siRNA the abundance of cilia decreased rapidly (black line), it remained virtually unchanged in cells where KV10.1 was knocked down (red). N=8-13.D. Time course of ciliary shortening after serum reintroduction. In the same experiments as in C, the length of the remaining cilia was measured automatically using ImageJ (FIJI). While ciliary length decreased with a similar time course in the siRNA-treated cells as in controls, cilia were longer in KV10.1-knockdown cells. A re-elongation of cilia was evident in both populations after 6 hours. Values are mean ± SEM for a number of cilia between 62 (control, 4.5 h) and 308 (both groups, 1.5 h).",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "A. Quantification of the amount of ciliated cells in primary embryonic fibroblasts from KV10.1 knockout mice. Actively growing cultures, cultures after 24 h serum starvation, and four hours after subsequent serum reintroduction were stained for the presence of cilia using anti-acetylated α-tubulin. An increase in frequency of cilia in the knockout cells was evident under all conditions, but especially marked in the ciliary resorption test (4h after serum reintroduction), indicating an influence of KV10.1 expression on deciliation.",
    "ncbi_link": "KV10.1: 16510"
  },
  {
    "caption": "B. Exogenous expression of human KV10.1 reverted the phenotype in MEFs. Cells obtained from three animals were transfected with KV10.1 or empty vector (mock), serum starved for 48 h and cilia were revealed by immunocytochemistry using anti-acetylated α-tubulin in the indicated number of images. KV10.1 expression decreased the frequency of ciliated cells.",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "C. MEFs from knockout mice did not show primary cilia when transfected with KV10.1. Cells were co-transfected with human KV10.1 and mVenus, serum starved for 48 hours and then fixed and stained for cilia (AcTub). Venus-positive cells did not show cilia. Scale bar: 25 µm.",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "D. In wild type MEFs, transfection with KV10.1 reduced the presence of primary cilia. When a gain-of-function mutant (L352V) that originates developmental defects in human patients was transfected, the frequency of cells with cilia was further reduced.",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "E. Sensitivity to SHH signaling was significantly increased in primary fibroblasts from KV10.1 knockout mice, in agreement with the higher abundance of primary cilia. Cells were serum starved and SHH was stimulated after 24 hours by addition of culture supernatant of SHH-expressing HEK293 cells. Expression of mRNA for Gli1 was used as reporter of SHH activation by qRT-PCR.",
    "ncbi_link": "Gli1: 14632
KV10.1: 16510"
  },
  {
    "caption": "A. Actively proliferating hTERT-RPE1 cells were transfected with scrambled or KV10.1 siRNA, and cell cycle distribution was determined using acridine orange staining. Knockdown of KV10.1 induces an increase in cells with DNA/RNA content compatible with G0 (rectangle). However, the quantitative increase (to approximately 10%) was insufficient to explain the abundance of ciliated cells (over 40%)",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "B. The proliferation marker Ki67 frequently coexists with primary cilia in KV10.1 knockdown cells. Exponentially growing cells were stained for acetylated α-tubulin (red, AvTub) and Ki67 (green). Nuclei were counterstained with Draq5 (blue). Scale bar: 10 µm.C. Quantification of the effects observed in B. Although the positivity for Ki67 (proliferating cells) and the presence of cilia were not always excluding each other even in cells transfected with control siRNA, KV10.1 knockdown increased the frequency of ciliated cells, while it reduced the amount of Ki67 positive, actively proliferating cells. Of those cells presenting a cilium, the fraction of simultaneously Ki-67-positive cells was much larger upon KV10.1 knockdown. Scale bar, 10 µm.",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "D. Primary cilia were present in cells actively synthesizing DNA (measured by EdU incorporation). Cells were transfected with siRNA against KV10.1, and 24 hours later were incubated in the presence of EdU for 4h before fixation. KV10.1 knockdown resulted in the presence of abundant EdU-positive and simultaneously ciliated cells, suggesting a decoupling between deciliation and cell cycle progression. Scale bar: 10µm",
    "ncbi_link": "KV10.1: 3756"
  },
  {
    "caption": "D. Images from primary cilia of MEFs from KV10.1 knockout mice obtained using mAb62 and a rabbit polyclonal anti acetylated a-tubulin antibody. No recognizable structures were stained by mAb62. Scale bar: 1 µm.E. In contrast, mAb62 did stain ciliary-related structures (acetylated-tubulin-positive) in wild type mice. Scale bar: 1 µm.",
    "ncbi_link": "KV10.1: 16510"
  },
  {
    "caption": "D. In the absence of serum, the C-terminus of KV10.1 reduced the number of cilia (maintained cells deciliated) also after deletion of the CLS (data for controls is reproduced from Figure 5A)The CLS is required to induce deciliation. When hTERT-RPE1 and 3T3 cells transfected with KV10.1 or KV10.1ΔCLS were serum starved, and serum was reintroduced after 24 hours for 4 h, KV10.1ΔCLS failed to reduce the fraction of ciliated cells.",
    "ncbi_link": "KV10.1: 3756
KV10.1: 16510"
  },
  {
    "caption": "E. The CLS is required for KV10.1-induced tumorigenesis. CHO cells were transfected with the indicated constructs and implanted into the flank of nude mice. KV10.1ΔCLS transfected cells did not induce larger tumors than the control.",
    "ncbi_link": "KV10.1: 16510"
  },
  {
    "caption": "A. Overexpression of cortactin compensated for the knockdown of KV10.1 in ciliary disassembly (4 h serum reintroduction after starvation).",
    "ncbi_link": "cortactin: 13043
KV10.1: 16510"
  },
  {
    "caption": "B. Deletion of the domain of KV10.1 responsible for interaction with cortactin abolished the effects of KV10.1 overexpression on the abundance of cilia.",
    "ncbi_link": "cortactin: 13043
KV10.1: 16510"
  },
  {
    "caption": "C. In mouse embryonic fibroblasts, active (phosphorylated) cortactin is increased as compared to wild type, possibly compensating the lack of KV10.1.",
    "ncbi_link": "KV10.1: 16510"
  },
  {
    "caption": "MIP of cerebral vessels of 3dpf Tg(kdrl:HRAS-mCherry)s916 embryo (grey LUT; inverted). Higher magnification panel showing two kugeln (arrowheads) arising from the middle mesencephalic central artery (MMCtA).",
    "ncbi_link": "mCherry: 
HRAS: 553656///550286
kdrl: 796537"
  },
  {
    "caption": "MIP of cerebral vessels of 4dpf Tg(fli1aep:CAAX-eGFP) embryo (grey LUT; inverted). Higher magnification panel shows a kugel (arrowhead) protruding from the posterior mesencephalic central artery (PMCtA).",
    "ncbi_link": "eGFP: 
fli1aep: 30619"
  },
  {
    "caption": "Single Z-plane micrograph of cerebral vessels of a 3dpf Tg(gata1:dsRed), injected with a Tol2-fli1a:myr-Cherry construct showing two kugeln (arrowheads) in the higher magnification panel protruding from the MMCtA.",
    "ncbi_link": "Cherry: 
dsRed: 
fli1a: 30619
gata1: 30481"
  },
  {
    "caption": "Inhibition of cardiac contraction by tnnt2a morpholino (MO) knockdown statistically significantly reduced kugel number per embryo (****p<0.0001; control n=20 embryos 5.10 ± 1.47 (mean ± s.e.m.), tnnt2a MO=18 embryos 0.06 ± 0.06 (mean ± s.e.m.); 3dpf; 3 experimental repeats; Mann-Whitney U test).",
    "ncbi_link": "tnnt2a: 58071"
  },
  {
    "caption": "Kugeln were studied in the double-transgenic Tg(fli1a:LifeAct-mClover)sh467, Tg(kdrl:HRAS-mCherry)s916. BLECs were mClover positive and mCherry-negative (BLECs - black arrowheads; kugeln - white arrowheads).",
    "ncbi_link": "mCherry: 
mClover: 
fli1a: 30619
HRAS: 550286///553656
kdrl: 796537"
  },
  {
    "caption": "Ccbe1 morpholino (MO) injection led to a loss of lymphatics (white arrowhead).",
    "ncbi_link": "Ccbe1: 555629"
  },
  {
    "caption": "Kugel number was not statistically significantly altered by ccbe1 morpholino (MO) knockdown (p = 0.3496; control MO n=22 embryos 0.95 ± 0.28 (mean ± s.e.m.), ccbe1 MO n=23 embryos 0.57 ± 0.14 (mean ± s.e.m.); 3dpf; 3 experimental repeats; Mann-Whitney U test).",
    "ncbi_link": "ccbe1: 555629"
  },
  {
    "caption": "Kugel diameter was not statistically significantly altered by ccbe1 MO knockdown (p = 0.8783; control MO n=21 kugeln from 22 embryos 7.75 ± 1.29 (mean ± s.e.m.), ccbe1 MO n=13 kugeln from 23 embryos 8.93 ± 2.35 (mean ± s.e.m.); 3dpf; 3 experimental repeats; Mann-Whitney U test).",
    "ncbi_link": "ccbe1: 555629"
  },
  {
    "caption": "The possible interaction of macrophages with kugeln was studied in the transgenic Tg(kdrl:HRAS-mCherry)s916, Tg(fms:GAL4.VP16)i186, Tg(UAS-E1b:nfsB.mCherry)il149, visualizing macrophages and the vasculature simultaneously. Coloured depth-coding indicates the different anatomical depths of kugeln and macrophages (ventral purple, dorsal white).",
    "ncbi_link": "GAL4: 
mCherry: 
nfsB: 
fms: 64274
HRAS: 550286///553656
kdrl: 796537"
  },
  {
    "caption": "A transgenic dll4 reporter line showed no indication of different dll4 expression at the sites of kugeln (white arrowheads pointing to kugeln; n=122 kugeln from 23 3dpf embryos; 2 experimental repeats).",
    "ncbi_link": "dll4: 563920"
  },
  {
    "caption": "Studying Notch signalling in the Notch reporter line Tg(TP1glob:venusPest)s940, showed high Notch levels in the mid-brain, but, again, no difference in expression at the sites of kugeln (n=45 kugeln from 19 4dpf embryos; 2 experimental repeats).",
    "ncbi_link": "venusPest: "
  },
  {
    "caption": "PolyA-seq was performed using N2A cells to examine the effect of downregulation of FUS and U1 snRNP on polyA site usage. Cells were treated with siRNA against Fus (siFus) and/or U1 antisense morpholino (U1AS). Control cells (Cont) were treated with both control siRNA and control antisense morpholino. A. Correlation of changes in polyA site usage between U1-inhibition and Fus-silencing. Fold change in the RPM of a polyA site between siFus and Cont (siFus/Cont) was plotted against that between U1AS and Cont (U1AS/Cont). Pearson's correlation coefficient (r) and the slope of the regression line are shown. B. Correlation of changes in polyA site usage between U1-inhibition alone and the combination of Fus-silencing and U1-inhibition. Fold change in the RPM of a polyA site between siFus+U1AS and Cont (siFus+U1AS/Cont) was plotted against that between U1AS and Cont (U1AS/Cont). Pearson's correlation coefficient (r) and the slope of the regression line are shown. A slope of 1.0 indicates that Fus-silencing has no additive effect on U1-inhibition.",
    "ncbi_link": "Fus: 233908
U1: 53607"
  },
  {
    "caption": " A) Heat map showing changes in RNA expression levels for various enzymes and regulators of central carbon metabolism in endogenous, CAF1-knockdown-induced (through p60 or p150 KD) 2-cell-like cells. Fold-changes relative to ESCs were calculated based on bulk RNA-seq data ",
    "ncbi_link": "p150: 27221
p60: 110749"
  },
  {
    "caption": " F) Glucose uptake rates upon knockdown of Gnpnat1 or a G6pdx were measured in ES, Zscan4+ and 2-cell-like cells. Measurements were quantified relative to the glucose uptake rate of ESCs transfected with a negative control siRNA. Shown are the mean ± s.d. of the indicated number of independent cell cultures, performed across 2 or more independent biological replicates each. ",
    "ncbi_link": "G6pdx: 14381
Gnpnat1: 54342"
  },
  {
    "caption": " C) Percentage of 2-cell-like cells obtained upon transfection of control or Dux-targeting siRNAs in control conditions or in combination with sodium acetate treatment. Measurements were obtained from 2 independent cell cultures, performed across 3 independent biological replicates. Boxes indicate the range between the first and third quantile, the band depicts the median and the whiskers extend no further than 1.5-times the interquartile range. Individual dots indicate the measurements obtained in each technical replicate. ",
    "ncbi_link": "Dux: 664783"
  },
  {
    "caption": "(c) The 9-bp deletion in ORRF1b (NSP1) that was detected in samples from two patients was confirmed in the GISAID database (below).",
    "ncbi_link": "NSP1: "
  },
  {
    "caption": "(d) Comparison of the ORF1b of the SARS-CoV-2 and SARS-CoV genomes with the 9-bp deletion region shown enlarged.",
    "ncbi_link": "ORF1b: "
  },
  {
    "caption": "(b) Up-regulated genes, with boxplots across all samples, include IFI6, ACE2, SHFL, HERC6, IFI27, and IFIT1, based on data from (c), which is the total set of DEGs. The full set is shown in an intersecting heat map, with a core set of up-regulated genes (orange) distinct form the set of down-regulated genes (purple), compared to genes that are not significantly differently expressed (grey) in any comparison (DESeq2, q-value <0.01, |logFC| >0.58).",
    "ncbi_link": "ACE2: 59272
HERC6: 55008
IFI27: 3429
IFI6: 2537
IFIT1: 3434
SHFL: 55337"
  },
  {
    "caption": "Untreated or Ruxolitinib  (10 µM)-treated PBMCs  from four individual donors were exposed to SARS-CoV or SARS-CoV-2 (MOI 0.5). PBMCs  inoculated with supernatant from Vero E6 cell cultures mixed with PBS  and OptiPro serum-free medium supplemented with 0.5% gelatine  were used as control condition (Mock). Supernatants and individual cell fractions were collected at indicated time points  post-inoculation and analyzed for: (E) Relative changes of cell-associated  viral genomic RNA quantities by Q-RT-PCR  and normalized to RNASEP  levels. Data information: Data were generated in four individual experiments using cells from at least four individual donors represented by different symbols, bars represent the mean, error bars indicate the S.E.M. Statistical significance was tested using paired Student's t-test comparing mock- and Ruxolitinib-treated samples. p-values > 0.05 were considered not significant and are not shown in the figure. h.p.e. = hours post-exposure Ruxo. = Ruxolitinib.",
    "ncbi_link": "RNASEP: "
  },
  {
    "caption": "RNA extracted from Ruxolitinib-treated or mock-treated, and SARS-CoV-, SARS-CoV-2- PBMCs  was analyzed for (A) IFIT1, (B) IFNA1  and IFNB1  mRNA expression by  Q-RT-PCR at indicated time points. Suspension and adherent cell fractions were analyzed separately, except at the four hours  time point. Values were normalized to cellular RNASEP  expression and are shown as fold change over mock-inoculated conditions. The dotted line indicates the expression level of mock-inoculated cell cultures and is set to 1. Data information: Data were generated in four individual experiments using PBMCs  from four or more individual donors represented by different symbols, bars represent the mean, error bars indicate the S.E.M (A-B Statistical significance between mock- and Ruxolitinib-treated samples was tested using paired Student's t-testing and comparing SARS-CoV to SARS-CoV-2-treated samples from the same donor and time points. P-values < 0.05 were considered significant (*), < 0.01 very significant (**) or ≥ 0.05 not significant (not shown).",
    "ncbi_link": "RNASEP: 
IFIT1: 3434
IFNA1: 3439
IFNB1: 3456"
  },
  {
    "caption": "(B) Representative UMAPs showing IFIT1  and ISG15  mRNA expression  in the indicated conditions. Data information: Data shown in this figure are based on the analysis of two donors.",
    "ncbi_link": "IFIT1: 3434
ISG15: 9636"
  },
  {
    "caption": "(D) Cell trajectory maps of indicated cell types with cells colored by expression  of the genes in an IFN-module gene set. Data information: Data shown in this figure are based on the analysis of two donors.",
    "ncbi_link": "IFN: 3467///56832///3439///101180976///282618///3445///3451///282616///3452///3447///3446///3448///3441///3444///3443///338376///3458"
  },
  {
    "caption": "(E) IFN  Module Score of  viral-RNA-negative (grey; 715 and 958 cells in SARS-CoV and SARS-CoV-2 exposed cultures, respectively), SARS-CoV-RNA-Positive (blue; 56 cells) and SARS-CoV-2-RNA-Positive (magenta; 173 cells) monocytes. Statistical significance was tested using a Wilcoxon rank sum test with continuity correction. P-values < 0.05 were considered significant (*), < 0.01 very significant (**) or ≥ 0.05 not significant Data information: Data shown in this figure are based on the analysis of two donors.",
    "ncbi_link": "IFN: 56832///3447///3467///3452///3458///282616///338376///3443///3451///3444///3445///3441///282618///101180976///3448///3439///3446"
  },
  {
    "caption": "(A-B) Western-Blotting (WB) of p53-negative lung cancer H1299 cells stably expressing (A) or transiently expressing (B) the indicated constructs. Post-translationally modified Δ133p53 and Δ160p53 isoforms are indicated with *.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) The same WB membrane containing lysates from R273Hp53-expressing A431cells was incubated with rabbit polyclonal CM-1 antibody and mouse monoclonal 1801 antibody against the N-terminus of p53. Detection using anti-rabbit IRDye 680LT (red) and anti-mouse IRDye 800CW (green) secondary antibodies confirmed that the Δ160p53 band corresponds to a C-terminal isoform of p53.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) Cell lines harbouring endogenous wild-type (A549) or R273H mutant (A431) p53 were treated or not with control siRNA (ctl) or siRNA targeting both p53 transcripts (ex6 and ex7), full-length mRNA only (ex2/3) or Δ133p53 mRNA only (in4) before lysis and WB.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(G) WB of H1299 cells stably expressing R273Hp53 and treated with DMSO, proteasome inhibitor MG132 or mRNA translation inhibitor cycloheximide (CHX). Shown are representative data of three independent experiments. The numbers in parenthesis indicate the amounts of protein for the indicated bands according to WB quantifications and normalization against α-tubulin or GAPDH and relative to the value indicated in bold and set to 1.0. In WBs for endogenous p53 cell lines the Δ160 lane is used as a marker lane showing Δ160p53 as transiently expressed in p53-null H1299 cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) Cell lines endogenously expressing mutant R273Hp53 (A431 and HT29) were treated with control siRNA (ctl) or siRNA targeting exon 7 of p53, submitted to endoplasmic reticulum (ER) stress by exposure to thapsigargin (Th) and then analysed for apoptosis by incubation with propidium-iodide (PI) and FACS analysis. Data was normalized against si ctl condition, which was set to 100.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(B and C) H1299 (C) lung cancer cell lines stably expressing the indicated constructs were counted with Trypan blue for several days following stress stimuli (thapsigargin (Th) for H1299). Data was normalized against 1st day values. Δ160p53 shows similar pro-proliferative capacities as mutant R273Hp53. On the other hand R273Hp53 lost pro-proliferative functions when deficient for Δ160p53 expression (M160AR273Hp53).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(D to G) H1299 cells transfected with the indicated constructs were submitted to ER stress (E and G) or cultured under regular conditions (D). Data was normalized against empty vector (E) or p53 (D) condition, which were set to 100. Cells were then analysed for apoptosis as in (A). Shown are representative data or averages + s.d. of three independent experiments (*P < 0.05, **P < 0.01, ***P < 0.005 and ^P > 0.05 compared to control (\"Th + si ctl\" or \"-\" ) or as indicated).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(D to G) H1299 cells transfected with the indicated constructs were submitted to ER stress (E and G), DNA-damage by 36h 3 μM etoposide (Eto) treatment (F). Data was normalized against empty vector (E) or p53 (D) condition, which were set to 100. Cells were then analysed for apoptosis as in (A). Shown are representative data or averages + s.d. of three independent experiments (*P < 0.05, **P < 0.01, ***P < 0.005 and ^P > 0.05 compared to control (\"Th + si ctl\" or \"-\" ) or as indicated).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) Adhesion assay shows that MCF10A cells stably expressing Δ133p53, Δ160p53, R273HΔ160p53 or missense mutant R273Hp53 adhere more strongly than control cells. Excluding Δ160p53 expression from the mutant background (M160A/R273Hp53) rescued control-cell phenotype. Scale bar represents 200 μm.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C and D) MCF10A human breast epithelial cells stably expressing the indicated constructs were cultured in matrigel. Control- and Δ133p53-expressing cells formed regular three-dimensional (3D) mammary acinar structures with hollow lumina but Δ160p53-, R273HΔ160p53 and to a smaller extent mutant R273Hp53-expressing cells formed acini with filled lumen and long invasive structures (n > 30 acini per experiment per condition).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C and D) MCF10A human breast epithelial cells stably expressing the indicated constructs were cultured in matrigel. Control- and Δ133p53-expressing cells formed regular three-dimensional (3D) mammary acinar structures with hollow lumina but Δ160p53-, R273HΔ160p53 and to a smaller extent mutant R273Hp53-expressing cells formed acini with filled lumen and long invasive structures (n > 30 acini per experiment per condition).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) WB of H1299 cells stably expressing Δ133p53 and treated with control morpholino oligos (Ctl-1 or Ctl-2) or antisense morpholino oligo targeting Δ160p53's translation initiation (MO)",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(B) A431 and HT29 cells expressing endogenous mutant R273Hp53 were treated with control morpholinos (Ctl-2 or Ctl-1) or antisense morpholino oligo targeting Δ160p53's translation initiation site (MO) before lysis and WB. wtp53-expressing A549 cells were used as reference for endogenous wtp53 expression levels. Δ160 lane was used as a marker lane showing Δ160p53 as transiently expressed in p53-null H1299 cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) Shown are the average Δ160p53 protein levels expressed in R273Hp53 versus other mutant p53cell lines that were treated with control morpholino (Ctl-1) or morpholino targeting 160p53's translation initiation site (MO). MO efficiently targets 160p53 in endogenous R273Hp53 cell lines. See also figure EV3 for the raw data.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(D-E) A431 (D) and HT29 (E) cells endogenously expressing mutant R273Hp53 were treated with control siRNA (si Ctl) or control MO (MO Ctl-2 or MO Ctl-1) or siRNA targeting exon 7 of p53 (si) or MO targeting Δ160p53's translation initiation site (MO), as indicated, submitted to endoplasmic reticulum stress by exposure to thapsigargin (Th) and then analysed for apoptosis by incubation with propidium-iodide (PI) and FACS analysis. wtp53-expressing A549 cells were similarly control-treated and used as comparison. Data was normalized against A549 cell condition, which was set to 100.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) A431 and HT29 cells endogenously expressing mutant R273Hp53 were treated with control morpholino Ctl-1 or morpholino targeting Δ160p53's translation initiation site (MO) and then assessed by confocal microscopy for invasion further than 30 μm through a Matrigel-fibronectin matrix towards EGF-supplemented growth media. The 30 μm plane is indicated and scale bars represent 100 μm. Quantifications are shown in the right panel.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "mRNA (C) in Acly in HSCs after the administration of 5-FU.",
    "ncbi_link": "Acly: 104112"
  },
  {
    "caption": "A. Immunoblot of cell extracts following depletion of WDR26, RanBP9, ARMC8, and GID4 using pools of siRNAs for 72 hr in HeLa Kyoto cells. Endogenous levels of the indicated proteins were monitored by western blotting (n=3).",
    "ncbi_link": "ARMC8: 25852
GID4: 79018
RanBP9: 10048
WDR26: 80232"
  },
  {
    "caption": "Western blotting of samples after ectopic overexpression of HBP1 (B) alone, or together with WDR26 or GID4 in HEK-293T cells. HBP1 levels were monitored after treatment of MG132 or DMSO for 10-12 h (n=3).",
    "ncbi_link": "GID4: 79018
HBP1: 26959
WDR26: 80232"
  },
  {
    "caption": "Western blotting of samples after ectopic overexpression of ZMYND19 (C) alone, or together with WDR26 or GID4 in HEK-293T cells. ZMYND19 levels were monitored after treatment of MG132 or DMSO for 10-12 h (n=3).",
    "ncbi_link": "GID4: 79018
WDR26: 80232
ZMYND19: 116225"
  },
  {
    "caption": "D. Western blotting of samples following ectopic overexpression of HBP1 either alone, or with full-length (FL) or WD40-truncated WDR26 (ΔWD40) in HEK-293T cells. HBP1 levels were monitored in cells treated with MG132 or DMSO for 12-14 h (n=3).",
    "ncbi_link": "HBP1: 26959
WDR26: 80232"
  },
  {
    "caption": "E. Western blot analysis of in vitro ubiquitinated HBP1 in the presence of wild type WDR26 (WT) or the WDR26 (ΔWD40) mutant (n=2).",
    "ncbi_link": "WDR26: 80232"
  },
  {
    "caption": "C. Transiently expressed FLAG-GID4 and HSS-tagged ARMC8 isoforms (α or β) in HEK293T cells. The presence of GID4 in isoform-specific ARMC8 immunoprecipitates was visualized by immunoblotting (left panels). The right panel shows a western blot of transiently expressed and immunoprecipitated HSS-WDR26 from HEK-293T cells and the presence of endogenous ARMC8 isoforms (α or β) was probed by immunoblotting (n=2).",
    "ncbi_link": "FLAG: 
ARMC8: 25852
GID4: 79018
WDR26: 80232"
  },
  {
    "caption": "A LNCaP cells were transfected with either control siRNA or two independent STAMP2 siRNAs, and membrane fractions of the cells were prepared followed by Western blotting analysis. STAMP1 is used as a loading control.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "E LNCaP cells stably expressing shRNA against STAMP2 or control shRNA were cultured for the indicated times, and the cell numbers were determined using a hemocytometer. n = 3, *P = 0.047; **P = 0.0046. Error bars indicate SD.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "F LNCaP cells stably expressing shRNA against STAMP2 or control shRNA were cultured in soft agar for 2 weeks as described in Materials and Methods. The plates were then stained and photographed.G Quantification of data from (F). n = 3, *P = 0.022. Error bars indicate SD.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "F LNCaP cells stably expressing shRNA against STAMP2 or control shRNA were cultured in soft agar for 2 weeks as described in Materials and Methods. The plates were then stained and photographed.G Quantification of data from (F). n = 3, *P = 0.022. Error bars indicate SD.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "H LNCaP cells stably expressing shRNA against STAMP2 or control shRNA were subcutaneously implanted into male SCID mice. Tumor size was measured after 8 weeks. n = 9, *P = 0.037. Error bars indicate SEM.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "A LNCaP cells were transfected with either control or STAMP2-specific siRNA. Two days after transfection, cells were subjected to cell cycle analysis as described in Materials and Methods. Representative histograms showing PI-stained cells are shown.B The proportion of cells in each stage of the cell cycle from the experiment in (A) is presented. Student's t-test was performed to analyze the statistical significance, n = 3. *P = 0.0002; **P = 0.0056; ***P = 0.0099. Error bars indicate SD.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "D LNCaP cells were transfected with either control or STAMP2-specific siRNA. Three days after transfection, cells were treated with either 50 ng/ml TRAIL or 20 μmol/l LY294002 (LY) for 24 h, or both agents for 6 h, and then subjected to TUNEL/FACS analysis. Representative histograms of TUNEL-stained cells are shown. FL1-H refers to the gating of the cells for the TUNEL staining with fluorescence measurement.E The extent of apoptosis from the experiment in (D) is presented. Student's t-test was performed to analyze the statistical significance, n = 3. *P = 0.027; **P = 0.0058; ***P = 0.0016. Error bars indicate SD.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "F LNCaP cells were transfected with either control or two independent STAMP2-specific siRNAs, ST2-1 and ST2-2. Three days after transfection, cells were treated in the same way as in (D). Whole-cell lysates were prepared and subjected to Western blot analysis with the indicated antisera.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "G LNCaP cells stably expressing either control or STAMP2 vector were treated in the same way as in (D). Cell lysates were prepared and subjected to Western blot analysis with the indicated antibodies.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "D CWR22 xenografts were grown in nude mice, and tumors were collected at different times after castration. mRNA was extracted from the tumors and used for qPCR analysis of STAMP2 expression. The results are presented as boxplots. Thick horizontal lines represent the median, with the box representing the upper and lower quartile. The whiskers represent the 5th and 95th percentiles, and the outlier is presented as an open circle. The statistical significance was determined by one-way ANOVA with a post hoc test. n = 3 in group week 0, 1, 2, and 4; n = 5 in refractory group. *P = 0.011; **P = 0.049. Error bars indicate SEM.",
    "ncbi_link": "STAMP2: 117167"
  },
  {
    "caption": "A LNCaP cells were transfected with either control or STAMP2-specific siRNA in the presence of 10−8 M R1881. RNA was isolated, and qPCR was used to determine ATF4mRNA levels. Student's t-test was used to analyze the statistical significance, n = 3. *P = 0.002. Error bars indicate SD.",
    "ncbi_link": "ATF4: 468
STAMP2: 79689"
  },
  {
    "caption": "C, D ATF4 expression in LNCaP (C) and 22Rv1 (D) cells stably expressing control shRNA or shRNA against STAMP2 was analyzed by Western blot analysis.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "C, D ATF4 expression in LNCaP (C) and 22Rv1 (D) cells stably expressing control shRNA or shRNA against STAMP2 was analyzed by Western blot analysis.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "E ATF4 expression in xenografted tumors of 22Rv1 cells stably expressing control shRNA or shRNA against STAMP2 was analyzed by qPCR. Student's t-test was used to analyze the statistical significance, n = 4. *P = 0.022; **P = 0.015; ***P = 0.044. Error bars indicate SEM.",
    "ncbi_link": "ATF4: 11911
STAMP2: 117167"
  },
  {
    "caption": "G The MSKCC Prostate Oncogenome cDNA microarray dataset was obtained from the cBio Cancer Genomics Portal. Analysis was performed as described in Materials and Methods. The expression levels of STAMP2 and ATF4, as well as two ATF4 target genes (ASNS and SLC7A11), are presented.",
    "ncbi_link": "ASNS: 440
ATF4: 468
SLC7A11: 23657
STAMP2: 79689"
  },
  {
    "caption": "A LNCaP cells were transfected with either control or ATF4 siRNA. Two days after transfection, cells were harvested and whole-cell lysates were made and used in Western blot analysis.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "B LNCaP cells were transfected with either control or ATF4 siRNA and were cultured for 2 weeks. The colonies formed were stained and photographed.C The area covered by the colonies on each plate in (B) was quantified and represented as percentage of the total area of the plate. *P = 0.0023.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "D Cell lysates of LNCaP cells stably expressing an empty vector (Vector) or a vector expressing ATF4 (ATF4) were prepared and subjected to Western blot analysis with the indicated antisera.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "G LNCaP cells were transfected with either control (Ctrl) or ASNS siRNA. The cells were then cultured for 2 weeks. The colonies formed were stained and photographed. Knockdown of ASNS was confirmed by Western blot analysis shown at the top.H Quantification of the data shown in (G). *P = 0.0087.",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "A 293T cells were transfected with plasmids expressing either an empty vector (Vec) or vectors expressing HA-tagged STEAP, STAMP1 (ST1), STAMP2 (ST2), or STAMP3 (ST3). Whole-cell extracts were prepared and subjected to Western blot analysis using anti-HA antibody or GAPDH as a loading control.",
    "ncbi_link": "STEAP: "
  },
  {
    "caption": "C 293T cells were transfected with different plasmids expressing either an empty vector (Vec) or vectors expressing His-tagged wild-type STAMP2 (WT) or three STAMP2 mutants (dGSR, H304L, or H397L) as indicated. Whole-cell extracts were prepared and used in Western blot analysis with anti-His antibody or GAPDH antibody as a loading control.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "E 293T cell line with Dox-inducible STAMP2 expression or vector control was generated. Western blot analysis confirmed STAMP2 expression in a Dox-inducible manner.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "G The cells with Dox-inducible STAMP2 expression from (E) were either left untreated or treated with Dox for 48 h. Prior to ferrireductase activity measurement, the cells were treated with or without DPI as indicated for 1 h. *P < 0.0001; **P = 0.0012; ***P = 0.048.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "I The cells with Dox-inducible STAMP2 expression from (E) were either left untreated or treated with Dox for 48 h. Then, the cells were treated with or without 10 μM DPI before being subjected to NBT staining. *P < 0.0001.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "A LNCaP cells stably expressing an empty vector (LN-Vec) or a vector expressing STAMP2 (LN-ST2) were established by lentivirus delivery. Cell lysates were prepared and subjected to Western blot analysis with the indicated antisera.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "C NBT staining was performed in LNCaP cells stably expressing either an empty vector (LN-Vec) or a vector expressing wild-type STAMP2 (LN-ST2/WT) or a STAMP2 mutant (LN-ST2/dGSR) as indicated. The stained cells were then photographed and quantified. *P = 0.004.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "D LNCaP cells were transfected with either scrambled siRNA (siCtrl) or siRNA against STAMP2 (siST2) and were cultured in the presence of 10 nM R1881 or vehicle for 2 days. Intracellular ROS levels were then measured by CellROX reagent staining. *P = 0.002. ns, not significant.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "E LNCaP cells stably expressing an empty vector (Vec), a vector expressing wild-type STAMP2 (WT), or a STAMP2 mutant (dGSR) were cultured, and the NADPH/NADP+ ratio was determined as described in Materials and Methods. *P = 0.015.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "F LNCaP cells were transfected with either control siRNA (siCtrl) or STAMP2 siRNA (siST2). Cells were then cultured for 2 days and harvested, and the NADPH/NADP+ ratio was determined as above. *P = 0.026.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "G LNCaP cells stably expressing wild-type STAMP2 were treated with or without DPI (1 μM) for 4 h, harvested, and used in the NADPH/NADP+ assay. *P = 0.018.",
    "ncbi_link": "STAMP2: 79689"
  },
  {
    "caption": "A LNCaP cells were implanted subcutaneously into nu/nu mice. Once tumors reached 5 mm in size, mice (n = 5 per group) were given nanoliposome-encapsulated control siRNA or STAMP2 siRNA as described in Materials and Methods. Tumor volumes were measured at the indicated time points. *P = 0.001.",
    "ncbi_link": "STAMP2: 117167"
  },
  {
    "caption": "D Zygotic grk2i283 mutant at 4dpf compared to wild type (N=80). Arrows indicate the position of swim bladder. Scale bar, 1mm",
    "ncbi_link": "grk2: 569403"
  },
  {
    "caption": "A Western blot analysis of the different forms of Gli2a in MZgrk2 embryos compared to wild type, shh mRNA and dnPKA mRNA injected wild type and cyclopamine (Cyc(A)) treated wild type 20hpf embryos. Gli2a-FL levels are low relative to Gli2aR levels in wild type embryos, but are elevated in response to pathway activation (shh and dnPKA mRNA injected). Gli2aR levels are increased while Gli2a-FL is undetectable in CycA treated and MZgrk2 mutant embryos. Probing the same blot with rabbit anti-GRK3 (which recognizes the zebrafish Grk2 protein) reveals a complete loss of full length Grk2 in MZgrk2 embryos. Probing with anti-γ-tubulin was performed as a loading control. Three biological replicates of this analysis were performed.",
    "ncbi_link": "PKA: 
grk2: 569403
shh: 30269"
  },
  {
    "caption": "B Phenotype of wild type, MZgrk2, and grk2-GFP mRNA injected MZgrk2 embryos at 24hpf (n=20 for each sample). The white lines indicate the shape of the somites (middle panels) and the separation of the eyes (right hand panels). Scale bar, 200μm",
    "ncbi_link": "grk2: 569403"
  },
  {
    "caption": "C In situ hybridisation of ptch2, nkx2.2a and olig2 transcripts in wild type, MZgrk2 and grk2-GFP injected MZgrk2 24hpf embryos. Each panel shows a full view of the embryo on the left and a cross sectional view of a somite on the right. (n=30 for each sample). Scale bars, 200μm (whole mounts), 50μm (sections).",
    "ncbi_link": "grk2: 569403
nkx2.2a: 30697
olig2: 325288
ptch2: 30181"
  },
  {
    "caption": "D Expression of Prox1a and Engrailed proteins (Eng) in somites of wild-type, MZgrk2 and grk2-GFP mRNA injected MZgrk2 embryos at 30hpf. Each panel shows Prox1a in green, Eng in red and the merge images with DAPI staining in blue. (n=10 for each sample). Scale bar, 50μm.",
    "ncbi_link": "grk2: 569403"
  },
  {
    "caption": "A Prox1a and Eng expression in the myotome of 30hpf wild type and MZgrk2 embryos injected with mRNAs encoding Shh, dnPKA or mSmoA1-GFP. Each panel shows Prox1a in green, Eng in red, and the merged images with DAPI staining in blue. The co-labelling for Prox1a and Eng (orange) is indicative of MP differentiation (n=30 for each sample) Scale bar, 50μm.",
    "ncbi_link": "PKA: 
grk2: 569403
Shh: 30269
Smo: 319757"
  },
  {
    "caption": "B Western blot showing levels of Gli2a-FL and Gli2a-R forms in 20hpf wild type and MZgrk2 embryos injected with mRNA encoding Shh, dnPKA or mSmoA1-GFP, respectively. γ-tubulin was used as loading control. Three biological replicates of this analysis were performed.",
    "ncbi_link": "PKA: 
grk2: 569403
Shh: 30269
Smo: 319757"
  },
  {
    "caption": "A Western blot analysis of GRK2, GLI1, PTCH1, and GLI3 protein levels in Flp-In-3T3 cells with lentiCRISPR of 4 different guide RNAs in presence or absence of SAG. α-tubulin was used as loading control. Guide RNA 2 was found to remove Grk2 efficiently and used for subsequent experiments. GLI3 panel shows both full-length (GLI3FL) and repressor form of GLI3 (GLI3R). (n=3)",
    "ncbi_link": "Grk2: 110355"
  },
  {
    "caption": "B, C Hh reporter activity assay for wild type and Grk2-/- cells. Cells were treated with PKA peptide inhibitor (PKI) and mutant form of PKA peptide inhibitor (PKI-M) respectively, in presence or absence of SHH (B) Cells were transfected with mSmoA1-GFP expressing constructs in the presence of SHH or SAG (C). Data represent the mean and ± SD (n=3). Unpaired Students t-test was used for analysis. ***P<0.001; **P<0.01; *P<0.05 and n.s. (not significant).",
    "ncbi_link": "Grk2: 110355
Smo: 319757"
  },
  {
    "caption": "A Expression of Prox1a (green) and the eng2a:GFP reporter (red) in otherwise wild-type 30hpf embryos injected with mRNA encoding wild type and mutant forms of mouse Smo. Ectopic MPs are indicated by fibres co-labelled with Prox1a and GFP; ectopic MFFs are labeled only with GFP. Images are representative of embryos in the following proportions of each sample: 28/28 (mSmo; mSmoA1; mSmoSD; mSmoKRA); 9/28 (mSmoA1SA); 12/28 (mSmoA1SD). Scale bar, 50μm.",
    "ncbi_link": "Smo: 319757"
  },
  {
    "caption": "B Average number of Prox1a+ve slow fibres in wild type embryos injected with mRNA encoding different forms of mSmo. Prox1 positive cells were quantified in 4 somites in each of 4 embryos for each sample. The error bars indicate SD. Unpaired Student's t-test was used to determine the statistical significance between uninjected embryos and the various Smo mutants (black asterisk); and between mSmoA1 and mSmoA1SA or mSmoA1SD (red asterisk). ***P<0.001; **P<0.01; *P<0.05 and n.s. (not significant).",
    "ncbi_link": "Smo: 319757"
  },
  {
    "caption": "C Prox1a and Eng expression in smohi1640 mutant embryos injected with mRNA encoding mSmo (n=10), mSmoSA (n=9) and mSmo14SA (n=6). Note the full recovery of SSFs and MPs compared to the un-injected controls. Scale bar, 50μm.",
    "ncbi_link": "Smo: 319757
smo: 319757"
  },
  {
    "caption": "D In situ hybridisation for transcripts of ptch2, olig2 and nkx2.2 in 24hpf smohi1640 mutant embryos injected with mRNA encoding mSmo and mSmoSA (n=6 for each sample). Scale bars, are 100μm (lateral view), 50μm (sections).",
    "ncbi_link": "nkx2.2: 30697
olig2: 325288
ptch2: 30181
Smo: 319757
smo: 30225"
  },
  {
    "caption": "E Hh reporter assay of the activity of wild type and mutant forms of mSmo in Smo-/- MEFs in response to Shh or SAG stimulation. Note that mSmoA1 shows constitutive activity in the absence of either Shh or SAG whereas mSmoKRA dose not; all mutants affecting phosphorylation failed to restore the response to Shh or SAG. Data represent the mean and ± SD (n=3). Unpaired Students t-test was used for analysis. ****P<0.0001; **P<0.01; and n.s. (not significant).",
    "ncbi_link": "Hh: 
Smo: 319757"
  },
  {
    "caption": "B Notochord cells of wild type embryos expressing GFP tagged wild-type and mutant forms of mSmo. Note the localisation to the PC (labeled with anti-AcTub; red) in each case (n=4 for each sample). Scale bar, 10μm.",
    "ncbi_link": "Smo: 319757"
  },
  {
    "caption": "C MZgrk2 18hpf embryos injected with mRNA encoding GFP-tagged wild type mSmo or mSmoSA (green) showing localisation to the PC (labeled with anti- AcTub; red) in myotomal cells. More Smo is localised to the PC in MZgrk2 mutants compared to wild type (panel A). Scale bar, 10μm.",
    "ncbi_link": "grk2: 569403
Smo: 319757"
  },
  {
    "caption": "B Prox1a (green) and Eng (red) expression in the myotome of 30hpf MZgrk2 embryos that were injected with mRNA encoding: Grk2K220R-GFP; Grk2K220M-GFP; Grk2D335N-GFP; Grk2ΔN7aa-GFP and mGrk2L4AV7AL8A-GFP. Merged panels show nuclear staining with DAPI in blue. (n=20 for each sample). Scale bar, 50μm.",
    "ncbi_link": "grk2: 569403"
  },
  {
    "caption": "C Hh reporter activity assay in wild type and Grk2-/- 3T3 cells transfected with the equivalent wild type and mutant kinase domain forms of mouse Grk2, Grk2K220R, Grk2K220M and Grk2D335N after 24h Shh-N and SAG treatment. Data represent the mean and ± SD (n=3). Unpaired Students t-test was used for analysis. ****P<0.0001; **P<0.01; *P<0.05; and n.s. (not significant).",
    "ncbi_link": "Hh: 
Grk2: 110355"
  },
  {
    "caption": "B PS1 FAD mutations alter substrate binding to the PS1 NTF in the γ-secretase cleavage domain. The weak PS1 A246E FAD mutation alters substrate interactions predominantly at V49 and L52, whereas the highly pathogenic PS1 L166P FAD mutation causes more broad changes over the whole cleavage domain. Arrows denote changes in binding of individual residues. Corresponding quantitation of substrate binding is shown below the immunoblots. Bars denote the mean ± S.E. (n = 3). Yellow line indicates level of substrate binding to PS1 WT, which was set to 1. Blue and red bars indicate increases or decreases in binding, respectively.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "qPCR measurements of JARID2 mRNA levels in different cell lines. The RNA levels were measured relative to 18S rRNA. Means and SEs are calculated over at least 2 independent experiments and 3 technical replicates. The data is represented as mean ± SE.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "Immunoblot showing that the ~80kDa band disappears upon treatment of HEK293T and HaCaT cells with siRNAs against exon 3 and exon 15 of JARID2 RNA. Non-silencing control (NSC) was used as a transfection control.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "qPCR measurements of RNA levels (n=3) for the three isoforms of JARID2 in HaCaT cells. The RNA levels are plotted relative to 18S rRNA. Level of JARID2 isoform-1 is significantly higher than that of isoform-2 (***P<0.001) and isoform-3 (****P<0.0001).",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "Agarose gel showing RT-PCR products amplified using primers in exon3 and exon15 (2.9kb) as well as RT-PCR product corresponding to JARID2 isoform-1 (3.7kb) amplified using the first (exon 1) and the last exon (exon18). Only one product at the right size is observed indicating that it is unlikely that JARID2 might be a product of an alternatively spliced isoform of JARID2.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "CRISPR-Cas9 knockout of JARID2 using a sgRNA guide designed to target main translation start site as seen in (E). Immunoblot revealed that ~80kDa form was removed from JARID2 KO lines.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "Effect of JARID2 removal on levels of differentiation markers Involucrin (IVL), Keratin-1 (KRT1) and Keratin-10 (KRT10) mRNAs as measured in qPCR experiment relative to 18S rRNA and the rescue using exogenous expression of ΔN-JARID2. The effect of exogenous expression of full-length JARID2 (FL-JARID2) in JARID2 knockout is also shown. Data from wildtype HaCaTs, two independent JARID2 knockout (KO1 and KO2) HaCaT lines as well as KO cells exogenously expressing empty vector control, ΔN-JARID2 and FL-JARID2 are shown. Levels of Involucrin (IVL), Keratin-1 (KRT1) and Keratin-10 (KRT10) mRNAs as above but measured on day 3 of differentiation.",
    "ncbi_link": "Involucrin: 3713
IVL: 3713
JARID2: 3720
Keratin-1: 3848
KRT1: 3848
Keratin-10: 3858
KRT10: 3858"
  },
  {
    "caption": "A metagene plot showing enrichment of full-length JARID2 in human induced pluripotent cells at down-regulated genes (blue) as compared to up-regulated genes (grey) in JARID2 KO cells. The plot is centered on Transcription Start Sites (TSS) of genes and distance from TSS is indicated on the x-axis.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "Metagene plots of average enrichment of EZH2 in ES cells and keratinocytes at down-regulated genes (blue) as compared to up-regulated genes (grey) in JARID2 KO cells. The plots are centered on Transcription Start Sites (TSS) of genes and distance from TSS is indicated on the x-axes.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "Levels of H3K27me3 in WT, JARID2 KO lines and JARID2 KO lines expressing ΔN-JARID2. Histone H3 and Ponceau staining is used as a loading control.",
    "ncbi_link": "JARID2: 3720"
  },
  {
    "caption": "A Up, Representative western blot from whole cell extracts showing H2AX protein levels in wt and junD-/- fibroblasts (Left) or in wt and Nfe2l2-/- fibroblasts (Right). Two representative clones, with their corresponding controls, are shown per genotype. H2B was used as negative control. Down, Bar plot showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown above). n ≥ 3 independent experiments.",
    "ncbi_link": "junD: 16478
Nfe2l2: 18024"
  },
  {
    "caption": "B Up, Representative western blot from kidney whole cell extracts showing H2AX protein levels in age-matched wt and junD-/- mice. Mice are 2 months old (young) and 18 months old (old) mice, respectively. Down, Bar plot showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown above). N ≥ 5 mice per age and per genotype.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "C Up, Representative western blot from kidney whole cell extracts, showing H2AX protein levels in 24 months old wt and junD-/- mice, either untreated (-) or treated with the anti-oxidant agent, N-acetyl-cysteine (NAC). Down, Bar plot showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown above). N ≥ 4 mice per treatment and per genotype.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "D,E Left, Representative western blots from whole cell extract showing γ-H2AX, H2AX protein levels and Kap1 phosphorylation (P-Kap1) in wt and junD-/- fibroblasts (D) or in wt and Nfe2l2-/- fibroblasts (E), after H2O2 exposure for the indicated times (hours, h). Right, Bar plots showing γ-H2AX and H2AX protein levels, as well as γ-H2AX/H2AX ratio as assessed by densitometry analysis of western blots (as shown on the left). n = 3 independent experiments.",
    "ncbi_link": "junD: 16478
Nfe2l2: 18024"
  },
  {
    "caption": "F,H Up, Representative western blots from whole cell extract showing γ-H2AX, H2AX protein levels and P-Kap1 in wt and junD-/- fibroblasts, following 2 Gy of γ-irradiation (F) for the indicated times (hours, h). Down, Bar plots showing γ-H2AX and H2AX protein levels, as well as γ-H2AX/H2AX ratio as assessed by densitometry analysis of western blots (as shown upper). n = 3 independent experiments.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "G,I Up, Representative γ-H2AX immunofluorescence (green) in wt and junD-/- fibroblasts before (-) or after γ-irradiation (2Gy, 45 min) (G). Blue signal corresponds to DAPI staining. Down, box-plots of large γ-H2AX foci per nuclei (diameter > 0.8 μm). At least 50 nuclei per genotype have been used for quantification.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "F,H Up, Representative western blots from whole cell extract showing γ-H2AX, H2AX protein levels and P-Kap1 in wt and junD-/- fibroblasts, after camptothecin (CPT) treatment (H) for the indicated times (hours, h). Down, Bar plots showing γ-H2AX and H2AX protein levels, as well as γ-H2AX/H2AX ratio as assessed by densitometry analysis of western blots (as shown upper). n = 3 independent experiments.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "G,I Up, Representative γ-H2AXimmunofluorescence (green) in wt and junD-/- fibroblasts before (-) or after after camptothecin (CPT) treatment for 1h (I).. Blue signal corresponds to DAPI staining. Down, box-plots of large γ-H2AX foci per nuclei (diameter > 0.8 μm). At least 50 nuclei per genotype have been used for quantification.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "A Bar plot showing the doubling time of wt and junD-/- fibroblasts.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "B Representative cell cycle distribution of asynchronous wt and junD-/- fibroblasts.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "C Bar plots showing the percentage of wt and junD-/- fibroblasts in G1, S and G2 phases of the cell cycle, following serum stimulation for the indicated times (hours, h), after 48h serum starvation.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "D Representative views of alkaline comet assays from wt and junD-/- fibroblasts either untreated or after 10Gy γ-irradiation for the indicated times (minutes, min).E Alkaline comet assays from wt and junD-/- fibroblasts at basal state. Left, Box-plots showing tail moments at basal state in wt and junD-/- fibroblasts. Right, Distribution of wt and junD-/- fibroblasts expressed as percentage of cells (%) according to categorized tail moments. At basal state, 16% of junD-/- cells exhibit tail moment higher than 5, while it is the case for only 3% of wt cells.F Alkaline comet assays from wt and junD-/- fibroblasts after 10Gy γ-irradiation. Box-plots showing tail moments at basal state in wt and junD-/- fibroblasts, following 10Gy γ-irradiation for the indicated times (minutes, min).G Distribution of wt and junD-/- fibroblasts expressed as percentage of cells (%) according to categorized tail moments, following 10Gy γ-irradiation for the indicated times (minutes, min).",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "H Surviving fraction of wt and junD-/- fibroblasts 7 days after 2Gy or 5Gy γ-irradiation, as assessed by clonogenic assay. Surviving fraction is expressed as percentage (%) of number of colonies after irradiation normalized with respect to untreated conditions.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "I Surviving fraction of wt and junD-/- fibroblasts either transfected with an empty vector (+ Ctl) or H2AX-expressing (+ H2AX) vector. Surviving fraction is expressed as percentage (%) of alive cells, 72 hours post-transfection.",
    "ncbi_link": "H2AX: 15270
junD: 16478"
  },
  {
    "caption": "A Up, Representative western blot from chromatin-free fraction or whole cell extracts, as indicated, showing H2AX protein levels in wt and junD-/- fibroblasts. Different amounts of loaded proteins and exposures (low- or high-exp) are presented, H2AX being easier to detect when associated with chromatin. Down, Bar plots showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown upper).",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "B Up, Representative western blot from chromatin-free fraction extracts showing H2AX protein levels in wt and junD-/- fibroblasts either untreated (-) or after 8h treatment (+) with proteasome inhibitor MG132. Jun is used as positive control for treatment efficiency. Down, Bar plots showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown upper).C Bar plot showing stabilization of H2AX protein in wt and junD-/- fibroblasts, as assessed by densitrometry analysis of western blots (as shown in B). Data are expressed as percentage (%) of H2AX protein levels after treatment with MG132 with respect to untreated conditions.",
    "ncbi_link": "junD: 16478"
  },
  {
    "caption": "D Representative western blots from whole cell extracts showing HA-tagged ubiquitin (Left) or Flag-tagged H2AX (Right) protein levels. wt and junD-/- fibroblasts were co-transfected with vectors encoding HA-tagged ubiquitin and Flag-tagged wild-type H2AX (WT), or K13-, K15-, K119-, or 9K-H2AX mutants. Flag-tagged H2AX proteins were then immunoprecipitated with Flag-specific antibody and incubated either with HA-specific antibody (Left) or Flag-specific antibody (Right). Two different exposures (low or high exp) are presented. * stands for the immunoglobulins.",
    "ncbi_link": "H2AX: 15270
junD: 16478"
  },
  {
    "caption": "E Left, Representative western blots showing H2AX-WT or H2AX-K119 protein levels (revealed using Flag-specific antibody) from whole cell extracts in wt and junD-/- fibroblasts. Cells were first transfected with Flag-tagged wild-type H2AX (H2AX-WT) or K119 H2AX mutant (H2AX-K119) and next treated with cycloheximide (CHX) for the indicated times (hours, h). Right, Bar graph showing H2AX-WT and H2AX-K119 protein half-life in wt and junD-/- fibroblasts, as indicated. Protein half-life has been calculated from the degradation curve of H2AX protein (based on densitometry analysis of western blots, as shown on the Left) by extrapolating its linear part.",
    "ncbi_link": "H2AX: 15270
junD: 16478"
  },
  {
    "caption": "F Left, Representative western blots showing H2AX-WT protein levels (revealed using Flag-specific antibody) from whole cell extracts in junD-/- fibroblasts co-transfected with Flag-tagged H2AX-WT construct and either non-targeting siRNA (siCtrl) or siRNA targeting RNF168 (siRNF168), RNF8 (siRNF8) or BMI1 (siBMI1). Efficiency of each siRNA has been verified and reached 60% of inhibition, in average, as shown for RNF168 (Up). Protein extracts were processed following cycloheximide (CHX) treatment for the indicated times (hours, h). Right, Bar graph showing the percentage (%) of decrease of H2AX-WT protein levels after 4h treatment with CHX (t=4) with respect to untreated conditions (t=0) in junD-/- fibroblasts transfected with specific siRNA, as indicated.",
    "ncbi_link": "BMI1: 12151
junD: 16478
RNF168: 70238
RNF8: 58230"
  },
  {
    "caption": "G Left, Representative western blots showing H2AX-WT or H2AX-K119 protein levels from whole cell extracts in junD-/- fibroblasts transfected either with Flag-tagged wild-type H2AX (H2AX-WT) or K119 H2AX mutant (H2AX-K119) and co-transfected with non-targeting siRNA (siCtrl) or siRNA targeting RNF168 (siRNF168). Cells were treated with cycloheximide (CHX) for the indicated times (hours, h) before protein extraction. Right, Bar graph showing H2AX-WT and H2AX-K119 protein half-life in junD-/- fibroblasts transfected with non-targeting siRNA (siCtrl) or siRNA targeting RNF168 (siRNF168), as indicated. Protein half-life has been calculated from the degradation curve of H2AX protein (based on densitometry analysis of western blots, as shown on the Left) by extrapolating its linear part.",
    "ncbi_link": "H2AX: 15270
junD: 16478
RNF168: 70238"
  },
  {
    "caption": "H Representative western blot showing RNF168, Flag-tagged H2AX (H2AX-FLAG) and endogenous H2AX (H2AX) protein levels from whole cell extracts in wt and junD-/- fibroblasts. Cells were first co-transfected with vectors encoding HA-tagged ubiquitin and Flag-tagged wild-type H2AX (WT), or K13-, K15-, K119-, or 9K-H2AX mutants. Flag-tagged H2AX proteins were next immunoprecipitated with Flag-specific antibody and incubated either with RNF168-specific antibody (Up) or H2AX-specific antibody (Down).",
    "ncbi_link": "H2AX: 15270
junD: 16478"
  },
  {
    "caption": "D Up, Representative western-blot showing H2AX protein levels from whole cell extracts in HCC70 TN BC cell line transfected with non-targeting siRNA (siCtrl) or an siRNA directed against H2AX (siH2AX). Actin is used as internal control for protein loading. Down, Bar plot showing H2AX protein levels as assessed by densitometry analysis of western blots (as shown above).",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "E Bar plot showing the percentage (%) of apoptotic cells as assessed by flow-cytometry analysis of annexin V and DAPI staining in HCC70 cell line transfected with non-targeting siRNA (siCtrl) or an siRNA directed against H2AX (siH2AX), and next treated with cisplatin for 72 hrs.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "J Box plots showing expression levels of representative NRF2-target genes in TN tumours with minor- or major-H2AX decrease, as indicated. Lines indicate Means and whiskers show 10-90 percentiles. ACOT7: Acyl-CoA Thioesterase 7; PGD: Phosphogluconate Dehydrogenase. AHR: Aryl Hydrocarbon Receptor; JAG1: Jagged1. P-values are from t-test.",
    "ncbi_link": "ACOT7: 11332
Acyl-CoA Thioesterase 7: 11332
AHR: 196
Aryl Hydrocarbon Receptor: 196
JAG1: 182
Jagged1: 182
PGD: 5226
Phosphogluconate Dehydrogenase: 5226"
  },
  {
    "caption": "(c) Larval brain lysate of wild-type (WT), hiw null mutant (hiwΔN) and Fsn mutant (Fsnf06595/Df(2R)7872) flies was subject to co-immunoprecipitation with antibody to Hiw (Hiw2b). Both the input and the immunoprecipitated complexes were analyzed by western blots with antibodies to Hiw or Rae1. The membrane was also blotted with antibody to β-tubulin to ensure equal amount of total proteins in the input samples. Full-length blots are presented in Supplementary Figure 8.",
    "ncbi_link": "Fsn: 36460
hiw: 32429"
  },
  {
    "caption": "(a) The gene structure of Rae1. The black-arrowed boxes indicate exons. A transposable element, P{GawB}NP3499, located ∼400 bp upstream of the first exon of Rae1 was used to generate imprecise excision mutants of Rae1. PCR analysis indicates that ∼900 bp and a ∼1.5-k bp DNA fragment in the Rae1 promoter region are missing in Rae1EX28 and Rae1EXB12, respectively. (b) Western blot analysis on Rae1 protein in the brain lysate of wild-type, Df(2R)5764/+, Rae1EX28/+, or late second instar Rae1EX28, Rae1EX28/Df(2R)5764(/Df) and Rae1EXB12 /Df(2R)5764 larvae. β-tubulin was used as the loading control. Full-length blots are presented in Supplementary Figure 9. (c) Quantification of Rae1 protein levels in the Rae1 heterozygous and homozygous mutant brains. Rae1 protein levels were first normalized to β-tubulin protein levels and are presented as percentage of wild-type level. *P 0.05, **P 0.001. Error bars denote s.e.m.",
    "ncbi_link": "Rae1: 37467"
  },
  {
    "caption": "(a) Representative confocal images of segment A3 muscle 6/7 synapses stained for both DVGLUT (green) and FasII (red), in late 2nd/early 3rd instar wild-type, Rae1EX28, Rae1EX28 presynaptic rescue (Rae1EX28; elav-Gal4/UAS-NTAP-Rae1) and Rae1EX28 wallenda suppression (Rae1EX28; wnd3) larvae. Scale bar represents 10 μm. (b,c) Quantification of bouton number (b) and size (c) in wild-type, Rae1EX28/Df, Rae1EX28, Rae1EX28 rescue, Rae1EX28; wnd3 suppression and hiwΔN larval NMJs (segment A3 muscle 6/7; n = 20, 21, 18, 20, 20 and 11, respectively, for bouton number; n = 271, 465, 548, 726, 486 and 826, respectively, for bouton size). There was no significant difference in either bouton number or bouton size between Rae1EX28 and Rae1EX28/Df (P > 0.1 for both comparisons). *P 0.001. Error bars denote s.e.m.",
    "ncbi_link": "Gal4: 
elav: 31000
hiw: 32429
Rae1: 37467
wallenda: 40143
wnd: 40143"
  },
  {
    "caption": "(a) Representative confocal images of muscle 4 synapses stained for both DVGLUT (green) and FasII (red) in wild-type, Rae1EX28/+, hiwND51, hiwND51; Rae1EX28/+, hiwΔN and hiwΔN; Rae1EX28/+ larvae. Scale bar represents 10 μm. (b) Quantification of bouton number at muscle 4 NMJs in wild-type, Rae1EX28/+, hiwND51, hiwND51; Rae1EX28/+, hiwΔN and hiwΔN; Rae1EX28/+ larvae (n = 27, 23, 42, 46, 23 and 25 cells, respectively). There was a significant increase in the number of boutons formed in hiwND51; Rae1EX28/+ compared with hiwND51 3rd instar larval NMJs (*P 0.001). The number of boutons in the hiwΔN; Rae1EX28/+ double mutant was not significantly different from that in hiwΔN (**P > 0.5), demonstrating a lack of enhancement of the hiwΔN phenotype by Rae1EX28/+. Error bars denote s.e.m.",
    "ncbi_link": "hiw: 32429
Rae1: 37467"
  },
  {
    "caption": "(a) Schematic presentation of NTAP-tagged (NT-) and HM-tagged (HM-) hiw transgenes encoding full-length, mutated or truncated Hiw proteins. Hiw functional domains are marked with colored boxes. The positions of amino-acid substitution in NT-HiwΔRING and the added amino acid residue necessary to maintain the reading frame in NT-Hiw-RCC1 and NT-Hiw-PHR are indicated. The right column summarizes the ability of the given hiw transgene to rescue the synaptic overgrowth phenotype in hiw mutants, to cause dominant negative overgrowth phenotype when expressed in wild-type background and to bind to Rae1. (b) Western blot analysis of fly brain lysate using antibody to TAP (PAP, Sigma) or Myc revealed the expression of wild-type and mutant hiw transgenes in predicted size.",
    "ncbi_link": "hiw: 32429"
  },
  {
    "caption": "(c) Representative confocal images of muscle 4 synapses stained for DVGLUT (green) and FasII (red) in wild-type (+/hiwND8; +/+; GS-elav-Gal4/+), NT-Hiw overexpression (+/hiwND8; UAS-NT-hiw/+; GS-elav-Gal4/+), NT-Hiw-NT overexpression (+/hiwND8; UAS-NT-hiw-NT/+; GS-elav-Gal4/+), NT-Hiw-CT1000 overexpression (+/hiwND8; +/+; GS-elav-Gal4/UAS-NT-hiw-CT1000), NT-Hiw-PHR overexpression (+/hiwND8; +/+; GS-elav-Gal4/UAS-NT-hiw-PHR), HM-Hiw-HindIII overexpression (+/hiwND8; UAS-HW-hiw-HindIII/+; GS-elav-Gal4/+), NT-Hiw-RCC1 overexpression (NT-hiw-RCC1/hiwND8; +/+; GS-elav-Gal4/+), or NT-Hiw-CT overexpression (+/hiwND8; +/+; GS-elav-Gal4/UAS-NT-hiw-CT) 3rd larval NMJs. Overexpression is indicated by an up arrow. Scale bar represents 10 μm. (d) Quantification of the number of boutons at muscle 4 NMJs in wild-type larvae or larvae overexpressing wild-type or mutant hiw transgenes (n = 23, 24, 26, 27, 26, 21, 25 and 27, respectively; *P 0.001). Error bars denote s.e.m.",
    "ncbi_link": "Gal4: 
elav: 31000
hiw: 32429
Hiw: 32429"
  },
  {
    "caption": "(a) Indicated NTAP-tagged hiw transgenes (described in Fig. 5) and a TAP only transgene were expressed in neurons under the control of the BG380-Gal4 driver. Larval brain lysates from each sample were subject to IgG pulldown. Both the inputs and the IgG pulldown complexes were analyzed by western blot using antibody to Rae1. Rae1 was present in all of the pulldown complexes except for those from TAP only, NT-Hiw-CT1000 and NT-Hiw-NT. Full-length blots are presented in Supplementary Figure 10. (b) Quantification of the interaction between various Hiw transgenic proteins and Rae1. Rae1 intensities in TAP pulldown blots were normalized to both the intensities and molecular weights of the corresponding TAP pulldown proteins.",
    "ncbi_link": "Gal4: 
hiw: 32429
Hiw: 32429
TAP: 39935"
  },
  {
    "caption": "(c) Representative confocal images of muscle 4 synapses stained for both DVGLUT (green) and FasII (red) in wild-type (BG380/Y;+/+; +/+), NT-Hiw-CT and GAP-GFP (BG380/Y; UAS-GAP-GFP/+; UAS-NT-hiw-CT/+), and NT-Hiw-CT and Rae1 (BG380/Y; +/+; UAS-NT-hiw-CT/UAS-GFP-Rae1) larvae. Scale bar represents 10 μm. (d) Quantification of number of boutons at muscle 4 NMJs in wild-type, NT-Hiw-CT overexpression (BG380/Y; +/+; UAS-NT-hiw-CT/+), NT-Hiw-CT and GAP-GFP, and NT-Hiw-CT and Rae1 (n = 24, 27, 32 and 26, respectively) larvae. Error bars denote s.e.m.; *P 0.001.",
    "ncbi_link": "GAP: 
Hiw: 32429
hiw: 32429
Rae1: 37467"
  },
  {
    "caption": "(a) Neuronal expression of neither Hiw nor Rae1 rescues the synaptic terminal overgrowth phenotype caused by the loss of function of the other gene. Quantification of the number of boutons in wild-type, Rae1EX28, Rae1EX28; Hiw rescue (Res) (Rae1EX28; elav-Gal4/UAS-GFP-hiw), hiwΔN and hiwΔN; Rae1 rescue (hiwΔN; elav-Gal4/UAS-NTAP-Rae1) larval NMJs (segment A3 muscle 6/7; n = 12, 12, 12, 7 and 11, respectively). (b) Representative confocal images of wild-type (BG380-Gal4/+; +/+; UAS-GFP-hiw/+) or Rae1 mutant (BG380-Gal4/+; Rae1EX28; UAS-GFP-hiw/+) ventral ganglions with UAS-GFP-hiw trangene expressed in neurons. The larvae were stained with antibodies to horseradish peroxidase (HRP, red) and GFP (green). Scale bar represents 10 μm.",
    "ncbi_link": "Gal4: 
elav: 31000
Hiw: 32429
hiw: 32429
Rae1: 37467"
  },
  {
    "caption": "(c) Western blots of total proteins extracted from wild-type, hiwΔN, Rae1EX28 and Rae1EX28 rescue (Rae1EX28; elav-Gal4/UAS-NTAP-Rae1) larval brains probed with indicated antibodies. Full-length blots are presented in Supplementary Figure 11.",
    "ncbi_link": "Gal4: 
elav: 31000
hiw: 32429
Rae1: 37467"
  },
  {
    "caption": "(d) Western blot analysis on total proteins extracted from hiwΔN, wild-type (C155-Gal4/+) and Rae1 expression (C155-Gal4/+; UAS-NTAP-Rae1/+) larval brains. Full-length blots are presented in Supplementary Figure 12. (e) Quantification of Hiw protein levels in the wild-type and the Rae1 expression larval brains (*P 0.001, based on seven independent experiments). Arrows indicate a 38-kDa endogenous Rae1 protein and the arrowheads indicate the 58-kDa transgenic NTAP-Rae1 protein. Error bars denote s.e.m.",
    "ncbi_link": "Gal4: 
hiw: 32429
Rae1: 37467"
  },
  {
    "caption": "(a) Representative confocal images of segment A3 muscle 6/7 synapses stained for both DVGLUT (green) and FasII (red), in wild-type, Rae1EX28, Rae1EX28; atg1/+, Rae1EX28; atg2/+ and Rae1EX28; atg18/+ wandering larvae. Scale bar represents 10 μm. (b) Quantification of the number of boutons in wild-type, atg1/+, atg2/+, atg18/+, Rae1EX28, Rae1EX28; atg1/+, Rae1EX28; atg2/+ and Rae1EX28; atg18/+ larval NMJs (segment A3 muscle 6/7; n = 12, 12, 12, 12, 12, 16, 12 and 21, respectively).",
    "ncbi_link": "atg1: 39454
atg18: 38913
atg2: 38344
Rae1: 37467"
  },
  {
    "caption": "(c) Western blot analysis on total proteins extracted from wild-type, Rae1EX28, Rae1EX28; atg1/+, Rae1EX28; atg2/+ and Rae1EX28; atg18/+ larval brains. The neural form of β-catenin (82 kDa, see Online Methods) was used as an internal control of neuronal proteins. Full-length blots are presented in Supplementary Figure 13. (d) Quantification of Hiw protein levels in wild-type, Rae1EX28, Rae1EX28; atg1/+, Rae1EX28; atg2/+ and Rae1EX28; atg18/+ larval brains (based on six independent experiments).",
    "ncbi_link": "atg1: 39454
atg18: 38913
atg2: 38344
Rae1: 37467"
  },
  {
    "caption": "(e) Representative confocal images of muscle 4synapses stained for both DVGLUT (green) and FasII (red) in wandering larvae of wild-type (C155-Gal4/+), Atg1Gap-GFP (C155-Gal4/+; UAS-Gap-GFP/+; UAS-Atg16B/+), and Atg1NTAP-Rae1 (C155-Gal4/+; UAS-NTAP-Rae1/+; UAS-Atg1/+). Scale bar represents 10 μm. (f) Quantification of the number of boutons at muscle 4synapses in wild-type, Rae1 expression (C155-Gal4/+; UAS-NTAP-Rae1/+), Atg1Gap-GFP and Atg1NTAP-Rae1 wandering larvae (segment A2-4, n = 28, 27, 33 and 34, respectively). Error bars denote s.e.m. *P 0.001, **P 0.05.",
    "ncbi_link": "Gal4: 
Gap: 
Atg1: 39454
Rae1: 37467"
  },
  {
    "caption": "D. Protein samples from Jurkat cells over expressing empty vector or AMPKS173A-S485A were immunoblotted for LC3 and LC3-II/Actin ratio was quantified and analyzed as shown. Data represent mean ± SE of three independent experiments.",
    "ncbi_link": "AMPK: "
  },
  {
    "caption": "F. Jurkat cells were transfected with DRP1S637A-GFP, 24h after transfection AICD was induced. 32h after AICD induction viability was determined cytofluorimetrically as the percentage of GFP-positive, annexin-V-PE-negative cells. Data represent mean ± SE of three independent experiments.",
    "ncbi_link": "DRP1: 10059"
  },
  {
    "caption": "I. Jurkat cells were transfected with DRP1K38A, 24h after transfection AICD was induced. 32h after AICD induction viability was determined cytofluorimetrically as the percentage AnnexinV/PI double negative cells. Data represent mean ± SE of three independent experiments.",
    "ncbi_link": "DRP1: 10059"
  },
  {
    "caption": "A. Splenocytes were isolated from Ambragt/+ and wt C57/BL6mice and activated as indicated in materials and methods. At day 7 after activation, AICD was induced with 0.1μg/ml of plate-bound anti-mCD3 (Clone 17A2). Apoptotic cells were detected 12h after AICD induction by flow cytometry as AnnexinV/PI double positive cells.",
    "ncbi_link": "Ambra: 228361"
  },
  {
    "caption": "B. Splenocytes were isolated from ATG7 fl/fl and wt C57/BL6mice. Activation of splenocytes and AICD were performed as previously described. At day 5 after activation, cells were infected with retroviral constructs expressing CRE recombinase. Where indicated, cells were pre-incubated with 100nM rapamycin for 24h before AICD induction. Apoptotic cells were detected 2h after AICD induction by flow cytometry as AnnexinV/PI double positive cells.",
    "ncbi_link": "CRE: 
ATG7: 74244"
  },
  {
    "caption": "C. Jurkat cells were transfected with scramble or ATG7 siRNA 24h before AICD induction. AICD was induced as described in materials and methods. Where indicated 100nM rapamycin was added at time 0h of AICD induction. Apoptotic cell death analysis was carried out as in (A), except that cells were analysed 32h after AICD induction. Data represent mean ± SE of five independent experiments.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "C) Expression patterns of rpb-9 in adult animals by RNA-sequencing.",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " Quantification of piRNA sensor expression. Representative DIC and fluorescence microscopy images of piRNA sensor expression in wild type (mjIs144) (D) and rpb‑9 (mj261) animals (two images with varying GFP expression are shown, scale bar = 20 µm) (E) ",
    "ncbi_link": "GFP: 
rpb‑9: 179178"
  },
  {
    "caption": "
 representative DIC and fluorescence microscopy images of piRNA sensor expression in the rpb-9 rescue (mj261; mjSi70) animals (two images with varying GFP expression are shown). Scale bar = 20 µm (G). 
",
    "ncbi_link": "GFP: 
rpb-9: 179178"
  },
  {
    "caption": " B) Representative fluorescence images of transgene expression in wild-type, rpb-9 (mj261), hrde-1 (tm1200) and prg1 (n4357); prg-2 (n4358) animals in the parental (P0) and inheriting (G1-G6) generations. Scale bar = 50 µm. C) Quantification of the percentage of desilenced individuals in wild-type, rpb-9 (mj261), prg-1 (n4357); prg-2 (n4358) and hrde-1 (tm1200) populations across generations. ",
    "ncbi_link": "hrde-1: 175535
prg1: 172515
prg-1: 172515
prg-2: 182072
rpb-9: 179178"
  },
  {
    "caption": " A) Differential expression analysis of transposable elements in rpb-9 (mj261) mutants versus wild type (polyA-selected RNA-seq libraries). [p<=0.01, log2(fold change)>=1, DESeq2 analysis] ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " C) Genome-wide differential gene expression analysis of rpb-9 (mj261) mutants versus wild-type (polyA-selected RNA-seq libraries). [p<=0.01, log2(fold change)>1 or <-1, DESeq2 analysis]. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " Pairwise correlation plots of rpb-9 (mj261) and prg-1 (n4357) (E), hrde-1 (tm1200) transcriptomes. Differentially expressed genes in rpb-9 (mj261) are shown in black, shared upregulated genes in red, shared downregulated genes in blue. The piRNA sensor transcript is highlighted in green. (Total RNA \"Ribo-Zero\" RNA-seq libraries). ",
    "ncbi_link": "hrde-1: 175535
prg-1: 172515
rpb-9: 179178"
  },
  {
    "caption": " Pairwise correlation plots of gonad-dissected prg-1 (n4357) transcriptomes. Differentially expressed genes in rpb-9 (mj261) are shown in black, shared upregulated genes in red, shared downregulated genes in blue. The piRNA sensor transcript is highlighted in green. (Total RNA \"Ribo-Zero\" RNA-seq libraries). ",
    "ncbi_link": "prg-1: 172515
rpb-9: 179178"
  },
  {
    "caption": " A-C) Analysis of RNA Pol II binding (RPB-1/AMA-1 ChIP-seq) at upregulated genes in rpb-9 (mj261) mutants, as defined in Figure 3C. Class I: upregulated genes with increased RNA Pol II binding (A); Class II: upregulated genes with invariant RNA Pol II binding (B); Class III: upregulated genes with reduced RNA Pol II binding (C). n=3 biological replicates are shown per each genotype. (PolyA-selected RNA-seq libraries). Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " A) Enrichment analysis of RPB-9-bound proteins in rpb‑9::ollas (mj604) versus wild type by IP/MS. [p<=0.05, log2(fold change)>1 or <-1, Welch t-test]. n=4 technical replicates (pooled). ",
    "ncbi_link": "ollas: 
RPB-9: 179178
rpb‑9: 179178"
  },
  {
    "caption": " B) Transgene transcript length is not affected in rpb-9 (mj261) mutants. Scheme of the gfp unspliced transcript showing the positions of RT-qPCR primers (top) and pairwise ratios (3′ to 5′) of unspliced gfp amounts along the transcript as indicated by the primer pairs (bottom). (n=3, error bars represent SD). ns= not significant (two-tailed t-test). ",
    "ncbi_link": "gfp: 
rpb-9: 179178"
  },
  {
    "caption": "  C) Transcriptome binning according to increasing 22G siRNA density in wild-type animals (grey, n=3). Mean normalized rpb-9 (mj261) mRNA reads (red, n=3) are overlaid with mean normalized wild-type mRNA reads (grey). (PolyA-selected RNA-seq libraries). The piRNA sensor transcript is indicated with red (rpb-9 (mj261)) and grey (wild type) dots. Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " D) Distribution of piRNA targets (as defined in (Bagijn et al, 2012) and of HDRE-1- and CSR-1-dependent 22G siRNAs across bins as defined in (C)).",
    "ncbi_link": "HDRE-1: 
CSR-1: 177591"
  },
  {
    "caption": " E) TE binning according to increasing 22G siRNA density in wild-type animals (grey, n=3). Mean normalized rpb-9 (mj261) mRNA reads (red, n=3) are overlaid with mean normalized wild-type mRNA reads (grey). (PolyA-selected RNA-seq libraries). The CEMUDR1 and Chapaev-2 transcripts are indicated with red (rpb-9 (mj261)) and grey (wild type) box plots. Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": "A) Expression levels of mature piRNAs in wild-type, rpb-9 (mj261), rpb-9 rescue (mj261; mjSi70) and prg-1 (n4357) animals (n=3, hyper-geometric test). Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers.",
    "ncbi_link": "prg-1: 172515
rpb-9: 179178"
  },
  {
    "caption": " B) Mature piRNA expression along chromosome IV coordinates (motif-dependent piRNA clusters I and II) in wild-type and rpb-9 (mj261) animals. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": "
  C) Northern blot quantification of mature piRNA 21UR-1 levels in wild-type, prg-1 (n4357), mut-7 (mj253) and rpb-9 (mj261) animals. 
",
    "ncbi_link": "21UR-1: 13209822
mut-7: 176347
prg-1: 172515
rpb-9: 179178"
  },
  {
    "caption": " D) Quantification of the levels of the mature piRNAs 21UR-4997 and 21UR-8099 by small RNA sequencing (raw reads normalized to library size, n=3). Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers.",
    "ncbi_link": "21UR-4997: 13205987
21UR-8099: 13194444"
  },
  {
    "caption": " A) Median precursor length shift of nascent (left) and nucleoplasmic (right) piRNA precursors in rpb-9 (mj261) mutants and rescue (mj261; mjSi70) animals compared to wild-type (n=2). Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. B) Distribution of nascent piRNA precursor lengths in rpb-9 (mj261) and rescue (mj261; mjSi70) animals compared to wild type. C) Peak positions of nascent piRNA precursor length distributions in 2000 subsamples of 5000 precursor sequences sampled without replacement. Central bands represent the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. D) Distributions of nucleoplasmic piRNA precursor lengths in rpb-9 (mj261) and rescue (mj261; mjSi70) animals compared to wild type. ",
    "ncbi_link": "rpb-9: 179178"
  },
  {
    "caption": " E) Distribution of 5′ ends of short capped RNA reads mapping to motif-dependent piRNA loci. Total counts of read 5′ ends mapping within a 50bp window of motif-dependent piRNA loci, aggregated by position relative to 21U-RNA 5′ U sites. A comparable enrichment of reads initiating 2 nt upstream of 21U-RNA 5′ U sites is observed across replicates and genotypes. ",
    "ncbi_link": "21U-RNA: 184627"
  },
  {
    "caption": " F) rpb-9 recruits Integrator at piRNA loci. Representative single-plan immunofluorescence images of Integrator (ints-6::GFP ) and PRDE-1 (prde-1::mCherry) localization in wild-type and rpb-9 (mj261) animals. Scale bar = 5 µm. G) Co-localization analysis of PRDE-1::mCHERRY and INTS-6::GFP foci in wild-type and rpb-9 (mj261) animals. Central bands represent the median, notches represent the confidence interval around the median, boxes represent the 25th and 75th percentiles and whiskers represent the lowest and highest values, excluding outliers. n (nuclei/genotype) > 16. (Welch's t-test, p = 1.7e-17).",
    "ncbi_link": "GFP: 
mCherry: 
ints-6: 24104403
prde-1: 184750
rpb-9: 179178"
  },
  {
    "caption": "(B) Proliferation of tumor tissue was determined by the percentage of Ki67-positive nuclei analyzed by flow cytometry. T: wt n=17, Casp-2-/- n=11, Raidd-/- n=10, Pidd1-/- n=8; NT: wt n=12, Casp-2-/- n=11, Raidd-/- n=7, Pidd1-/- n=5. N-numbers refer to biological replicates.",
    "ncbi_link": "Casp-2: 12366
Raidd: 12905
Pidd1: 57913"
  },
  {
    "caption": "(E) The number of binucleated hepatocytes per field was counted on H&E stained paraffin sections of PBS treated wt and Pidd1-/- mice at t(0h) and at t(48h) after PBS or DEN treatment. N-numbers refer to biological replicates.",
    "ncbi_link": "Pidd1: 57913"
  },
  {
    "caption": "(G) Centriole number was quantified with respect to the number of nuclei per cell in wt and Pidd1-/- livers at the time points described in (E); n=3 biological replicates.",
    "ncbi_link": "Pidd1: 57913"
  },
  {
    "caption": "(A) Binucleation was assessed blinded in H&E stained sections of murine non-tumor (NT) and tumor tissue (T) T: wt n=14, Casp-2-/- n=11, Raidd-/- n=10, Pidd1-/- n=10; NT: wt n=8, Casp-2-/- n=10, Raidd-/- n=8, Pidd1-/- n=9. N-numbers refer to biological replicates.",
    "ncbi_link": "Casp-2: 12366
Raidd: 12905
Pidd1: 57913"
  },
  {
    "caption": "Binucleation was assessed blinded in H&E stained sections of murine non-tumor (NT) and tumor tissue (T) also shown in (B). T: wt n=14, Casp-2-/- n=11, Raidd-/- n=10, Pidd1-/- n=10; NT: wt n=8, Casp-2-/- n=10, Raidd-/- n=8, Pidd1-/- n=9. N-numbers refer to biological replicates.",
    "ncbi_link": "Casp-2: 12366
Raidd: 12905
Pidd1: 57913"
  },
  {
    "caption": "C, D (C) Representative histograms of nuclei stained for DNA, which were isolated from non-tumor and tumor tissue of wt and Casp2-/- mice. These animals are marked as red "x" in the quantification shown in (D) were the degree of polyploidy is reflected as percentage of octaploid nuclei (T: wt n=17, Casp-2-/- n=11, Raidd-/- n=10, Pidd1-/- n=8; NT: wt n=12, Casp-2-/- n=11, Raidd-/- n=7, Pidd1-/- n=5). N-numbers refer to biological replicates.",
    "ncbi_link": "Casp-2: 12366
Casp2: 12366
Raidd: 12905
Pidd1: 57913"
  },
  {
    "caption": "Copy number variations were determined using whole genome sequencing of 30 nuclei "mini-bulks" isolated from Casp2-/- or wt tumors (n=11 per genotype). Diploid and tetraploid pools of tumor cell nuclei were analyzed separately. A, B (A) Representative dot plots show the degree of aneuploidy and heterogeneity and are quantified in (B, empty symbols). Data are represented as median, statistical significance determined by one-way ANOVA with multiplicity correction (Sidak-Holm); * p≤0.05, ** p≤0.01. N-numbers refer to biological replicates.",
    "ncbi_link": "Casp2: 12366"
  },
  {
    "caption": "(B) mRNA expression analysis of the PIDDosome components in the TCGA Provisional LIHC data set across disease stages. Patients are divided based on the p53 mutation/deletion (mut/del) status. Statistical significance was determined using two-way ANOVA with Tukey's post-hoc analysis. The central band represents the median, the boxes indicate the 25th and 75th percentile, the whiskers are the 5th and 95th percentiles, statistical significance was defined as * p≤0.05, ** p≤0.01.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) The same data set was analyzed for recurrence-free survival based on high or low expression of CASP2, RAIDD or PIDD1 divided at the median. Statistical significance was determined using a Log-rank test.",
    "ncbi_link": "CASP2: 835
RAIDD: 8738
PIDD1: 55367"
  },
  {
    "caption": "(B) E2F target genes expression was analyzed for correlation with expression of CASP2, RAIDD and PIDD1 using Spearman's correlation coefficient. The central band represents the median, the boxes indicate the 2nd and 3rd quartile, and the whiskers are 1.5 times the interquartile range (n=200 genes).",
    "ncbi_link": "CASP2: 835
RAIDD: 8738
PIDD1: 55367"
  },
  {
    "caption": "Correlation (Pearson) of CASP2 mRNA with transcript levels of Ki67 in the TCGA data set.",
    "ncbi_link": "CASP2: 835
Ki67: 4288"
  },
  {
    "caption": "Correlation (Pearson) of RAIDD and PIDD1 mRNA with transcript levels of Ki67 in the TCGA data set.",
    "ncbi_link": "RAIDD: 8738
Ki67: 4288
PIDD1: 55367"
  },
  {
    "caption": "(A) siRNA knockdown of Tollip in SH-SY5Y cells was performed over 72 hours, with cells reverse transfected with siRNA oligos specific for Tollip (or mock) for 24 hours before a second transfection was performed for a further 48 hours. Knockdown was confirmed by western blotting.",
    "ncbi_link": "Tollip: 54472"
  },
  {
    "caption": "(B) After knockdown of Tollip, SH-SY5Y cells were treated with 5 μM antimycin A/10 μM oligomycin B (AO) or 25 μM Antimycin A (AA) alone for 2 hours, then fixed and stained for PDH E2/E3bp (green), TOM20 (red) and nuclei (blue). Images were captured using widefield immunofluorescence microscopy. Zoom insets represent 4x magnification and arrowheads indicate TOM20-positive MDVs.",
    "ncbi_link": "Tollip: 54472"
  },
  {
    "caption": "(F) Images captured using super-resolution radial fluctuations (SRRF) microscopy showing both TOM20 (arrowheads) and PDH (arrows) MDVs in SH-SY5Y cells after Tollip siRNA knockdown. Left side images are the first in each of the original widefield image stacks. Scale bar for zoom images is 0.5 μm.",
    "ncbi_link": "Tollip: 54472"
  },
  {
    "caption": "(A) TOM20-positive MDV formation was induced in SH-SY5Y by siRNA knockdown of Tollip. MDVs were defined as TOM20+ve/Cytochrome c (Cyt c)-ve via immunofluorescence microscopy, which indicated some colocalisation with Parkin (arrowheads).",
    "ncbi_link": "Tollip: 54472"
  },
  {
    "caption": "(B) SH-SY5Y cells were transfected with GFP-Tollip for 24 hours, then treated with 5 μM antimycin A/10 μM oligomycin B (AO) or AO/100 μM bafilomycin A1 (BfnA1) for 2 hours prior to fixation and immunostaining. Antibodies specific to GFP (green), Parkin (red) and ubiquitin (blue) were used.",
    "ncbi_link": "GFP: 
Tollip: 54472"
  },
  {
    "caption": "C) GFP-Tollip/Parkin colocalisation was quantified from cells under steady state conditions or treated with AO and AO/BfnA1 by counting overall GFP puncta and GFP puncta positive for Parkin per cell, across 3-6 GFP-transfected cells/condition, per experiment (n = 3). Results are represented as a percentage of Tollip puncta positive for Parkin.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(G) The percentage of GFP-Tollip puncta positive for Parkin was quantified from immunofluorescence images immunostained for GFP and Parkin from WT, R78A, and CUE mutant expressing cells across 3-6 GFP-transfected cells/ condition, per experiment (n = 3; *p=0.0162, **p=0.0034, ****p<0.0001).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(H) The percentage of ubiquitin puncta positive for Tollip was quantitated from immunuofluorescence images immunostained for ubiquitin and GFP from WT, R78A, and CUE mutant expressing cells across 3-6 GFP-transfected cells/condition, per experiment (n = 3; *p=0.0382, **p=0.0068).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(I) The percentage of ubiquitin puncta positive for Parkin was quantitated from immunuofluorescence images immunostained for ubiquitin and Parkin from WT, R78A, and CUE mutant expressing cells across 3-6 GFP-transfected cells/condition, per experiment (n = 3; *p=0.0232, **p=0.0062).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(J) The percentage of GFP-Tollip/Parkin vesicles positive for ubiquitin were quantitated from immunofluorescence images immunostained for GFP, Parkin, and ubiquitin from WT, R78A, and CUE mutant expressing cells across 3-6 GFP-transfected cells/condition, per experiment (n = 3; **p=0.0070).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) HeLa cells expressing mycBioID-Tollip and HA-Parkin were either left untreated or treated with 5 μM antimycin A/10 μM oligomycin B (AO) or AO/100 μM bafilomycin A (BfnA1) for 6 hours in the presence of biotin. Cells were lysed and streptavidin pulldowns performed overnight to isolate biotinylated proteins. Proteins in whole cell extracts and pulldowns from each condition were then separated by SDS-PAGE and membranes probed with specific antibodies. Immunoblotting for Tom1 and mycBioID-Tollip were used as positive controls. Cells cultured in media lacking biotin were used as a negative control to assess background levels. Biotinylation of Parkin suggested Tollip specifically interacted with Parkin under these conditions.",
    "ncbi_link": "Bio: 
myc: 
Tollip: 54472"
  },
  {
    "caption": "(C) Hela cells co-expressing GFP-Tollip and HA-Parkin were either left untreated or treated with AO for 2 hours prior to lysis. Cell lysates were subjected to either a normal rabbit IgG IP or HA IP and western blot analysis was performed using antibodies against Parkin and GFP.",
    "ncbi_link": "GFP: 
HA: 
Parkin: 5071
Tollip: 54472"
  },
  {
    "caption": "(D) HeLa cells expressing mycBioID-Tollip containing the CUE domain mutation (CUEmut) and HA-Parkin were subjected to biotinylation and streptavidin pulldowns, followed by western blot analysis.",
    "ncbi_link": "Bio: 
myc: 
Tollip: 54472"
  },
  {
    "caption": "(E) HeLa wild-type (WT), Tom1 KO and ATG5 KO cells expressing mycBioID-Tollip and HA-Parkin underwent the same conditions as those above and immunoblotted for the indicated proteins.",
    "ncbi_link": "Bio: 
myc: 
ATG5: 9474
Tollip: 54472
Tom1: 10043"
  },
  {
    "caption": "(A) Cells were reverse transfected with Parkin or Tom1 siRNA oligos for 24 hours before a second transfection was performed for a further 48 hours, then fixed and stained with antibodies specific to TOM20 (green) and PDH E2/E3bp (red). Nuclei are labelled with Hoechst (blue). Zoom insets represent 5x magnification and arrowheads indicate TOM20-positive MDVs.",
    "ncbi_link": "Parkin: 5071
Tom1: 10043"
  },
  {
    "caption": "(E) Western blot analysis of lysates harvested from SH-SY5Y wild-type (empty vector) and CRISPR generated Parkin KO cells. Immunoblot analysis was performed using antibodies against Parkin and GAPDH.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(F) Immunofluorescence microscopy was performed on SH-SY5Y wild-type and Parkin KO cells either untreated or treated with AO for 2 hours. Cells were immunostained for TOM20 (red), PDH E2/E3bp (blue), and LAMP1 (green). Zoom insets represent 5x magnification. Circles indicate TOM20 MDVs positive for LAMP1 and arrowheads indicate TOM20 MDVs negative for LAMP1. Scale bar represents 10 µm.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(H) HeLa cells transiently transfected with HA-Parkin were subjected to mitochondrial stress by treatment with 25 μM antimycin A (AA) for 2 hours, then fixed and stained with antibodies specific to HA, PDH and TOM20. TOM20+ve/PDH-ve MDVs were quantified in cells that were either expressing or not expressing HA-Parkin (n = 12-14 cells per condition from 3 independent experiments).",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(I) Hela cells stably coexpressing BioID-Tollip and either HA-Parkin WT or Δ1-76 (ΔUBL) were incubated with and without biotin in the presence of AO for 6 hours prior to being subjected to cell lysis and streptavidin pulldowns. Western blot analysis was performed on lysate inputs and streptavidin pulldowns (Streptavidin PD) using antibodies against the indicated proteins or epitope tags.",
    "ncbi_link": "Bio: 
HA: 
Parkin: 5071
Tollip: 54472"
  },
  {
    "caption": "(A-B) siRNA knockdown of Tollip or Parkin in SH-SY5Y cells was performed over a 72 hour period, then 18 hours prior to treatment cells were transfected with GFP-2xFYVE to label endocytic membranes. Cells were treated with 25 μM antimycin A (AA) for 2 hours then fixed and immunostained with antibodies specific to PDH E2/E3bp (red) and TOM20 (blue). Arrowheads denote TOM20+ve/PDH-ve MDVs that colocalise with GFP-2xFYVE and arrows denote TOM20+ve/PDH-ve MDVs that do not.",
    "ncbi_link": "FYVE: 
GFP: 
Parkin: 5071
Tollip: 54472"
  },
  {
    "caption": "(E) siRNA knockdown of Parkin was performed in SH-SY5Y cells followed by 25 μM AA for 2 hours prior to fixation and immunostaining with antibodies specific to TOM20 (green), Tollip (red) and Cytochrome c (blue). We observed Tollip colocalisation with TOM20+ve/PDH-ve MDVs (denoted by arrowheads), which was still maintained following Parkin siRNA knockdown.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(F) SH-SY5Y cells were transfected with GFP-Tollip and treated with 5 μM antimycin A/10 μM oligomycin B (AO) or AO/100 μM bafilomycin A (BfnA1) for 2 hours prior to fixation and immunostaining with antibodies specific to GFP (green), Rab7a (red) and PDH E2/E3bp (blue). (G) Quantification of GFP-Tollip/Rab7a colocalisation using Pearson's correlation.",
    "ncbi_link": "GFP: 
Tollip: 54472"
  },
  {
    "caption": "(B) Quantitation of the prevalence of Tollip clusters in HEK293 WT or Tom1 KO cells treated with AO for 2 hours. The percentage of cells with vesicular clusters were quantified from an average of 50 cells for each condition from 5 independent experiments.",
    "ncbi_link": "Tom1: 10043"
  },
  {
    "caption": "(D-E) SH-SY5Y cells were transfected with either wild-type GFP-Tollip (WT), GFP-Tollip lacking its N-terminus (∆Nterm), or GFP-Tollip containing a CUE domain mutation (CUEmut) then treated with AO for 2 hours. Cells were fixed and immunostained with antibodies specific to GFP (green) and LAMP1 (red).",
    "ncbi_link": "GFP: 
Tollip: 54472"
  },
  {
    "caption": "(F) The extent of colocalisation between GFP-Tollip and LAMP1 from untreated and AO treated SH-SY5Y cells were quantitated from immunofluorescence images and represented as a Pearson's correlation (2-3 cells per experiment, from 2 independent experiments). (G-I) The extent of colocalisation between GFP-Tollip and LAMP1 in Tom1 KO (G), ATG5 KO (H), and VPS35 KO (I) compared to wild-type (WT) HeLa cells was quantified from immunofluorescence images immunostained for GFP and LAMP1 and represented as a Pearson's correlation (2-3 cells per experiment, from 3 independent experiments). Western blot analysis of lysates harvested from wild-type (WT) alongside either Tom1 KO (G) or VPS35 KO (I) Hela cells was performed using antibodies specific to the indicated proteins.",
    "ncbi_link": "ATG5: 9474
Tom1: 10043
VPS35: 55737"
  },
  {
    "caption": "(A) A subset of TOM20+ve/PDH-ve MDVs are trafficked to the lysosome. siRNA knockdown of Tollip was conducted in SH-SY5Y cells over a 72 hours period prior to treatment with 5 μM antimycin A/10 μM oligomycin B (AO) or 25 μM antimycin A (AA) for 2 hours. Cells were then fixed and stained with antibodies specific to LAMP1 (green), PDH E2/E3bp (red) and TOM20 (blue). Arrows denote TOM20+ve/PDH-ve MDVs colocalising with LAMP1, whereas arrowheads denote MDVs that do not colocalise with LAMP1. (B) From immunofluorescence images, the total number of TOM20+ve/PDH-ve MDVs were counted as well as the number of TOM20 MDVs that colocalised with LAMP1 to calculate the % of TOM20 positive MDVs colocalising with LAMP1 per cell (n = 25-32 cells per condition from 3 independent experiments).",
    "ncbi_link": "Tollip: 54472"
  },
  {
    "caption": "(C) siRNA knockdown was performed in SH-SY5Y cells, then 18 hours prior to fixation cells were transfected with GFP-Tollip wild-type (WT), ∆Nterm, CUEmut, or R78A. Cells were fixed and immunostained for PDH E2/E3bp (red) and TOM20 (blue). Arrowheads denote TOM20+ve/PDH-ve MDVs. (D) Quantification of TOM20 MDVs per cell was performed by eye (n = 11-14 cells per mutant from 2 independent experiments). Cells expressing a GFP-Tollip construct were identified using the GFP channel. Surrounding cells not expressing GFP were counted as the Tollip siRNA only population.",
    "ncbi_link": "GFP: 
Tollip: 54472"
  },
  {
    "caption": "A Generation of myeloid cells  genetically inactivated for Elp3. Elp3  mRNA and protein levels were assessed by Real-Time PCR  with extracts isolated from peritoneal macrophages of Elp3Control and Elp3∆Mye mice. mRNA levels in Elp3Control mice  were set to 1 and levels in other experimental conditions were relative to that after normalization with Gapdh  mRNA levels (n = 3 mice; mean +/- SD, Student T test, ***= p< 0.001). An anti-Elp3 western blot  (WB) is also illustrated. The anti-Gapdh blot  is shown for normalization purposes.",
    "ncbi_link": "Elp3: 74195
Gapdh: 14433"
  },
  {
    "caption": "C and D Defective mTORC2  signaling upon Elp3  deficiency in myeloid cells.  Peritoneal macrophages from Elp3Control and Elp3∆Mye mice  were isolated and cultured ex-vivo. They were untreated or stimulated with a combination of LPS  (100 ng/ml) and IFNγ  (50 ng/ml) for the indicated periods of time  and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "F mTORC2  activation by M1 polarization signals relies on Ctu2. Control and Ctu2-depleted bone marrow-derived macrophages  (BMDMs) (SiRNA-mediated depletions) were treated or not with IFNγ  (50 ng/ml) and LPS  (100 ng/ml) and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Ctu2: 66965"
  },
  {
    "caption": "C Elp3  deficiency in myeloid cells  exacerbates the decrease of colon  length upon DSS  administration (n = 7 mice; mean +/- SD, **= p< 0.01).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "E More severe histological  score in mice  lacking Elp3  in myeloid cells  upon DSS  administration. Representative intestinal crypts from the indicated genotypes are illustrated. The histological  score was established as described in methods (n = 5 mice  per genotype; mean +/- SD, Student T test, *= p< 0.05).",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "F Increased infiltration of iNOS+/CD68+ cells upon DSS  administration in  Elp3∆Mye mice. The percentage of iNOS+ in CD68+ cells was established in both genotypes treated with DSS  (n = 7 mice  per genotype; mean +/- SD, Student T test, **= p< 0.01). Anti-iNOS  and -CD68 immunofluorescence  analyses carried out in  intestinal crypts from both genotypes are illustrated.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "G Patients  suffering from  ulcerative colitis (UC) show reduced levels of both Elp1  and Elp3. The central band represents the mean value of relative expression  in the investigated cohort. Boxes represent 75th and 25th percentile. Whiskers represent maximum and minimum values before the upper and lower fence, respectively (**= p< 0.01, ***= p<0.001) (GSE9452-GEO DataSets, Definition of an ulcerative colitis  pre-inflammatory state).",
    "ncbi_link": "Elp1: 8518
Elp3: 55140"
  },
  {
    "caption": "E Rictor  but not Raptor  deficiency impairs Elp3  expression. BMDMs  were transfected with the indicated siRNAs and the resulting cells were treated or not with  IL-4 (10 ng/ml)/IL-13  (10 ng/ml) for 24 hours. Cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Rictor: 78757
Raptor: 74370"
  },
  {
    "caption": "Elp3    deficiency in myeloid cells impairs multiple signaling pathways triggered by  IL-4 (H, ,  IL-13  (H) or by both cytokines (H). Peritoneal macrophages isolated from the indicated mouse  genotypes were untreated or stimulated with IL-4 (10 ng/ml) (H, IL-13 (10 ng/ml) (H) or with both cytokines (H) for 8 hours (H) and the resulting cell extracts were subjected to WB analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "J Elp3  deficiency in myeloid cells impairs multiple signaling pathways triggered by  IL-4 I and J) Peritoneal macrophages isolated from the indicated mouse  genotypes were untreated or stimulated with IL-4  (10 ng/ml) , I and J), or for the indicated periods of time  (I and J) and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "L Elp3   promotes M2 macrophage polarization.  Peritoneal macrophages  isolated from the indicated mouse  genotypes were untreated or stimulated with  IL-4/IL-13 (10 ng/ml) for 24 hours and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "B Defective induction of Pparγ  by  IL-4/IL-13 upon Elp3  deficiency. Cell extracts from  peritoneal macrophages of Elp3Control and Elp3∆Mye mice  treated or not with IL-4/IL-13 were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "A The induction of Ric8b  expression by IL-4 relies on Elp3. BMDMs  from the indicated genotypes were treated or not with  IL-4 (10 ng/ml) up to 24 hours and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "B Elp3  promotes Ric8B   mRNA translation. BMDMs  from Elp3Control and Elp3∆Mye mice  were treated by  IL-4  for 24 hours, followed by a treatment with 10 μg/ml puromycin  for 5 minutes. To detect newly synthesized Ric8b  proteins, a Puro-PLA  assay was conducted. Representative images detecting Ric8b (Red) and α-Tubulin+ microtubules  (green) in BMDMs  are illustrated. On the right, the graph shows a quantification of signals for Ric8b  in α-Tubulin+ areas. A random of six different areas were counted (6 technical replicates, mean +/- SD, Student's t-test, *= p< 0.05).",
    "ncbi_link": "Elp3: 74195
Ric8B: 237422"
  },
  {
    "caption": "C Ric8b  is a direct target of Elp3. BMDMs  from Elp3Control and Elp3∆Mye mice  were infected with a lentiviral GFP  construct (negative control), Flag-Ric8b  WT or with Flag-Ricb  MUT, as indicated and the resulting protein extracts were subjected to WB  analyses to assess Ric8b  and Elp3  protein levels. Gapdh  was used as a loading control.",
    "ncbi_link": "Flag: 
GFP: 
Elp3: 74195
Ric8b: 237422
Ricb: 237422"
  },
  {
    "caption": "D and E Ric8b  promotes  IL-4-dependent mTORC2  activation. Control or Ric8b-depleted BMDMs  were treated or not with IL-4 (10 ng/ml) for the indicated periods of time  and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Ric8b: 237422"
  },
  {
    "caption": "C Elp3  promotes mitochondrial  translation. BMDMs  from the indicated genotypes were treated or not with  IL-4/IL-13 (10 ng/ml) for the indicated hours and the resulting cell extracts were subjected to WB  analyses.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "D Elp3  expression in myeloid cells maintains the pool of tumor-associated macrophages (TAMs). The number of TAMs, defined as CD301+/F4/80+ cells among F4/80+ cells was quantified in  intestinal crypts from both Apc+/Min Elp3Control and Apc+/Min Elp3∆Mye mice  (n = 5 mice  per genotype; mean +/- SD, Student T test, *= p< 0.05). Representative immunofluorescence  analyses are illustrated.",
    "ncbi_link": "Apc: 11789
Elp3: 74195"
  },
  {
    "caption": "Immunoblots (left) and quantifications normalized to control (right) of VPS16, VPS33A and VPS11 in lysates from fibroblasts transduced with a lentivirus to express VPS16 or control (empty vector).",
    "ncbi_link": "VPS16: 64601"
  },
  {
    "caption": "Analysis of the early endosome marker EEA1 in fibroblasts transduced with control or VPS16-expressing lentivirus by confocal microscopy. (A) Representative confocal micrographs. Scale bar, 20 μm. (B) Quantification of EEA1-stained puncta number and intensities (ca 80 cells analyzed for each of n=3 biological replicates).",
    "ncbi_link": "VPS16: 64601"
  },
  {
    "caption": "Confocal micrographs of fibroblasts transduced with control or VPS16-expressing lentivirus and labeled with LysoTracker. Scale bar, 20 μm. Quantification of LysoTracker-stained puncta number and intensities (ca 80 cells analyzed for each of n=3 biological replicates).",
    "ncbi_link": "VPS16: 64601"
  },
  {
    "caption": "Myelination, as reported using the Tg(mbp:gfp-caax) transgenic, is significantly reduced in vps16 crispants. The yellow box indicates the region assessed in D. Scale bar 100 μm. Bar graphs represent data as mean ±SEM. Statistical comparisons by Mann-Whitney U tests (n=6). ** p < 0.01.",
    "ncbi_link": "gfp: 
vps16: 798985"
  },
  {
    "caption": "Identification of the ENU-induced hearing loss pedigree MPC169, subsequently named clarinet. ABR phenotyping of pedigree Muta-Ped-C3PDE-169 at 3-months of age identified 8 mice with elevated hearing thresholds (red triangles) compared to their normal hearing colony mates (n=61, black triangles). Indeed, all eight affected mice were found to not respond to the highest intensity stimulus (90 dB SPL) at the three frequencies tested, or the click stimulus, and so their thresholds are shown as 95 dB SPL.",
    "ncbi_link": "clarinet: 624224"
  },
  {
    "caption": "Averaged ABR thresholds for Clrn2clarinet/del629 compound heterozygotes at P21, showing significantly elevated thresholds compared to Clrn2+/+, Clrn2clarinet/+ and Clrn2del629/+ control colony mates. All five Clrn2clarinet/del629 mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least one frequency/click stimulus. Data shown are mean ± s.d. ***p<0.001, one-way ANOVA (Please see Appendix supplemental table 1 for exact P-values).",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Regional plot of p values for SNP association with hearing difficulty around the CLRN2 gene locus. The genes within the region are annotated, and the direction of the transcripts is shown by arrows. Colouring is based on linkage disequilibrium (LD) across the region with the most associated SNP, rs35414371, shown in purple.",
    "ncbi_link": "CLRN2: 624224"
  },
  {
    "caption": "RT-PCR analysis in P30 mice showing the presence of Clrn2 transcripts in the inner ear, eye, but not in brain or muscle. β-actin was used as a positive control.",
    "ncbi_link": "β-actin: 
Clrn2: 624224"
  },
  {
    "caption": "Clrn2 transcripts could be detected in both inner (IHCs) and outer (OHCs) hair cells of P15 wild-type mice. Otoferlin (Otof) and oncomodulin (Ocm) transcripts were used as positive controls for IHCs and OHCs, respectively. Ocm transcripts were only present in the OHC lysate, demonstrating that the IHC sample had not been contaminated with OHCs.",
    "ncbi_link": "Clrn2: 624224
Ocm: 18261
oncomodulin: 18261
Otof: 83762
Otoferlin: 83762"
  },
  {
    "caption": "Auditory phenotyping of clarinet mice at P16 (C), P21 (D) ABR threshold measurements show that Clrn2clarinet/clarinet mice (red) exhibit a severe-to-profound hearing loss affecting all frequencies tested. At 16 kHz in Clrn2clarinet/clarinet mice, the mean ABR hearing thresholds vary from 55-65 dB SPL at P16, 60-90 dB SPL at P21, and to 80-100 dB SPL at P28 and P42. Age-matched Clrn2+/+ (black) and Clrn2clarinet/+ (grey) controls display thresholds within the expected range (15-45 dB SPL) at all frequencies and time-points tested. At P16, all eight Clrn2clarinet/clarinet mice exhibited recordable ABR responses for each frequency tested and the click stimulus. For the longitudinal ABR study, at P21 and P28 three of the seven Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least one frequency-specific/click stimulus. By P42, five of the Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least two frequency-specific/click stimuli. ABR data shown are mean ± s.d. ***p<0.001, one-way ANOVA.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Auditory phenotyping of clarinet mice at P28 (E) and P42 (F). ABR threshold measurements show that Clrn2clarinet/clarinet mice (red) exhibit a severe-to-profound hearing loss affecting all frequencies tested. At 16 kHz in Clrn2clarinet/clarinet mice, the mean ABR hearing thresholds vary from 55-65 dB SPL at P16, 60-90 dB SPL at P21, and to 80-100 dB SPL at P28 and P42. Age-matched Clrn2+/+ (black) and Clrn2clarinet/+ (grey) controls display thresholds within the expected range (15-45 dB SPL) at all frequencies and time-points tested. At P16, all eight Clrn2clarinet/clarinet mice exhibited recordable ABR responses for each frequency tested and the click stimulus. For the longitudinal ABR study, at P21 and P28 three of the seven Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least one frequency-specific/click stimulus. By P42, five of the Clrn2clarinet/clarinet mice were found to not respond at the highest intensity stimulus (90 dB SPL) for at least two frequency-specific/click stimuli. ABR data shown are mean ± s.d. ***p<0.001, one-way ANOVA.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Averaged DPOAE responses for clarinet mice at P28, showing significantly reduced responses in Clrn2clarinet/clarinet mutants at all frequencies tested. DPOAE data shown are mean ± s.d. *p<0.02, **p<0.01, one-way ANOVA. Please see Appendix supplemental table 1 for exact P-values.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Vestibular behavioural tests (swim tests, contact-righting, trunk-curl, and platform). The Clrn2clarinet/clarinet mice (red, P28, n=5, and P60, n=7) have no vestibular dysfunction, displaying similar performances to age-matched control Clrn2clarinet/+ mice (grey, P28, n=3, and P60, n=7). Being similar, the values at P28 and P60 were combined. Electroretinogram (ERG) measurements from control Clrn2clarinet/+ (grey) and mutant Clrn2clarinet/clarinet (red) mice. Each trace in B and C is representative of an ERG response from the eye of age-matched Clrn2clarinet/+ and Clrn2clarinet/clarinet mice, showing no significant difference in a- or b-wave amplitudes. (D-F) The lack of change in ERG amplitude responses in Clrn2clarinet/clarinet mice (aged 3 or 6-7 months), regardless of the test conditions: scotopic (D,E), or photopic (F), indicate normal photoreceptor kinetics and no change in the sensitivity of photoreceptor cells.",
    "ncbi_link": "Clrn2: 624224
clarinet: 624224"
  },
  {
    "caption": "Electroretinogram (ERG) measurements from control Clrn2clarinet/+ (grey) and mutant Clrn2clarinet/clarinet (red) mice. Each trace in B and C is representative of an ERG response from the eye of age-matched Clrn2clarinet/+ and Clrn2clarinet/clarinet mice, showing no significant difference in a- or b-wave amplitudes. (D-F) The lack of change in ERG amplitude responses in Clrn2clarinet/clarinet mice (aged 3 or 6-7 months), regardless of the test conditions: scotopic (D,E), or photopic (F), indicate normal photoreceptor kinetics and no change in the sensitivity of photoreceptor cells.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Confocal microscopy images of whole-mount preparations of mid-basal cochlear sensory epithelia from Clrn2clarinet/+ (A) and Clrn2clarinet/clarinet (B) P6 mice immunostained for actin. Despite lack of clarin-2, the developing sensory epithelium of mutants is similar to that of heterozygous controls.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Confocal microscopy images of whole-mount preparations of cochlear sensory epithelia from Clrn2clarinet/+ (C), Clrn1-/- (D), and Clrn2clarinet/clarinet (E) P6 mice immunostained for stereocilin (green) and actin (red). Unlike the fragmented immunostaining in Clrn1-/- mice (mirroring the fragmentation of the hair bundle), stereocilin immunostaining in Clrn2clarinet/clarinet mice reflects the normally V-shaped bundles of OHCs, similar to Clrn2clarinet/+ OHCs.",
    "ncbi_link": "Clrn1: 229320
Clrn2: 624224
clarinet: 624224"
  },
  {
    "caption": "Representative scanning electron micrographs of the sensory epithelium of Clrn2clarinet/+ (F) and Clrn2clainet/clarinet (G) P8 mice, showing no apparent differences in the gross patterning of IHCs and OHCs. Arrowheads in a,b (white),f and g (black) illustrate the convex shape of the apical circumference of OHCs.",
    "ncbi_link": "clainet: 624224
clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Pseudo-coloured scanning electron micrographs of individual outer and inner hair cell bundles from clarinet mice at P8 and P16, showing that gross morphology of OHC and IHC bundles is similar between Clrn2+/+ and Clrn2clarinet/clarinet mice. Representative images from the mid region of the cochlear spiral are shown and close-up views illustrate the three full rows, tallest (red), middle (blue) and short (yellow), of stereocilia in IHC and OHC hair bundles. At P8 and P16 (upper panels in A and B), the three stereocilia rows are observed in Clrn2clarinet/clarinet OHCs (A) and IHCs (B), although the shortest and middle row of IHC stereocilia appear less prolate compared to controls. (C,D) Distribution of individual stereocilia measures across genotypes at P8 and P16.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "The OHC stereocilia measurements at both P8 and P16 (C) show a significant difference in height of Clrn2+/+ stereocilia compared to Clrn2clarinet/clarinet in: e.g. for the shortest row at P8: Clrn2+/+: 0.6188 ± 0.0944 p.µm (n=27); Clrn2clarinet/clarinet: 0.2948 ± 0.1029 p.µm (n=27) (p<0.0001, Mann-Whitney ranks comparison), and at P16: Clrn2+/+: 0.579 ± 0.06179 p.µm (n=27); Clrn2clarinet/clarinet: 0.07282 ± 0.1626 p.µm (n=27) (p<0.0001, Mann-Whitney ranks comparison). Note the amount of value points equal to zero at P16. (D) Conversely, IHC stereocilia measurements at P8 and P16 did not show a difference between Clrn2+t/+ and Clrn2clarinet/clarinet in: for the shortest row at P8: Clrn2+/+: 0.8808 ± 0.1753 p.µm (n=27); Clrn2clarinet/clarinet: 0.9313 ± 0.1217 p.µm (n=27) (p=0.2244, unpaired t-test); and at P16: Clrn2+/+: 0.6784 ± 0.1171 p.µm (n=23); Clrn2clarinet/clarinet: 0.6063 ± 0.1855 p.µm (n=26) (p=0.2436, Mann-Whitney ranks comparison).",
    "ncbi_link": "Clrn2: 624224
clarinet: 624224"
  },
  {
    "caption": "Sensory hair cell bundle patterning and measurements in clarinet mice Pseudo-coloured scanning electron micrographs of individual OHC (left panels) and IHC (right panels) hair bundles from clarinet mice at P28. Clrn2clarinet/clarinet mutants have only two rows of OHC stereocilia, and the middle row of stereocilia is less uniform in height compared to controls. The middle and short rows of stereocilia in Clrn2clarinet/clarinet IHC bundles appear fewer in number, and heterogeneous in height. Scale - 2 µm.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Schematic representation of the auditory sensory organ, illustrating the positioning of the electrode used for injectoporation of GFP-tagged clarin-2 construct into cochlear supporting and hair cells. (B-F) Top and side views of representative images of supporting cells (asterisk) and hair cells expressing clarin-2. In supporting cells, GFP-tagged clarin-2 (green) was distributed diffusely throughout the cytoplasm (A,B). By contrast, in all injectoporated hair cells, the majority of clarin-2 was observed in the apical stereocilia (C-E). Scale - 2 µm.",
    "ncbi_link": "GFP: 
clarin-2: 624224"
  },
  {
    "caption": "Confocal images of IHC and OHC hair bundles of Clrn2clarinet/clarinet mice and heterozygous littermates at P6 immunostained for PDZD7 (A, green) and whirlin (B, green) and actin (red in both figures). The PDZD7 immunostaining is normally restricted to the base of stereocilia in both Clrn2clarinet/+ and Clrn2clarinet/clarinet P6 mice (A). Whirlin immunostaining is properly located at the stereocilia tips of IHC and OHC hair bundles (B).",
    "ncbi_link": "Clrn2: 624224
clarinet: 624224"
  },
  {
    "caption": "Harmonin-b immunostaining in IHC hair bundles. In Clrn2clarinet/clarinet mice (D), the harmonin-b immunoreactive puncta (green) were still observable on the stereocilia, but unlike in age-matched heterozygote littermates (C), were located much closer to the tip of stereocilia. The two diagrams in (C) and (D) illustrate the position of harmonin-b immunostaining (green) corresponding to the site of the upper attachment point of the tip link (UAPTL), facing the tip link. The bright green signal outside stereociliary bundles are non-specific. The change of harmonin-b localization along the stereocilium in Clrn2clarinet/clarinet mice is illustrated further by line scan (E) and quantification (F) analyses. The insets in (E) show images of individual stereocilia used for the line scan signal analysis. The harmonin-b immunoreactive puncta were located within 850 ± 28 nm distance from the tip of the tallest stereocilia in Clrn2clarine/+ mice (n=31 hair bundles from 5 mice) (F), and within 575 ± 23 nm in Clrn2clarinet/clarinet mice (n=35 hair bundles from 5 mice).",
    "ncbi_link": "clarine: 624224
clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Cochlear whole-mounts from P21 clarinet mice, labelled with the IHC pre-synaptic ribbon marker Ribeye (red) and the post-synaptic density marker GluR2 (green), showing a similar number of total and matched Ribeye-positive and GluR2-postive puncta in Clrn2clarinet/clarinet mutant cochleae compared to Clrn2clarinet/+ littermates, which is reflected in puncta counted per five hair cells (H) n = 4 per genotype.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Saturating MET currents recorded from P6 Clrn2clarinet/+ (A) and Clrn2clarinet/clarinet (B) apical-coil OHCs by applying sinusoidal force stimuli of 50 Hz to the hair bundles at −121 mV and +99 mV. The driver voltage (DV) signal of ± 40 V to the fluid jet is shown above the traces (positive deflections of the DV are excitatory). The holding potential was −81 mV. Extracellular Ca2+ concentration was 1.3 mM. Arrows and arrowheads indicate the closure of the MET currents (i.e. resting MET current) elicited during inhibitory bundle displacements at hyperpolarized and depolarized membrane potentials, respectively. Dashed lines indicate the holding current, which is the current at the holding membrane potential.",
    "ncbi_link": "Clrn2: 624224
clarinet: 624224"
  },
  {
    "caption": "Average peak-to-peak current-voltage curves recorded from Clrn2clarinet/+ (grey, P6, n=7) and Clrn2clarinet/clarinet (red, P6-7, n=9) apical coil OHCs.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Saturating MET currents recorded from a P7 Clrn2clarinet/+ (F) and a P8 Clrn2clarinet/clarinet (G) apical-coil IHC using the same experimental protocol described above.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Average Po of the MET current measured in apical coil IHCs at the membrane potential of −121 mV and + 99 mV from Clrn2clarinet/+ (P7, n=3) and Clrn2clarinet/clarinet (P7-8, n=6) apical-coil IHCs.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Potassium currents recorded from mature Clrn2clarinet/+ (A, P15) and Clrn2clarinet/clarinet (B, P16) apical-coil OHCs. Currents were elicited by depolarizing voltage steps (10 mV nominal increments) from -144 mV to more depolarized values from the holding potential of -84 mV. Note that the current characteristic of mature OHCs, The size of IK,n, measured in isolation as the deactivating tail currents (difference between instantaneous and steady-state inward currents) for voltage steps from the holding potential to −124 mV, was 545 ± 115 pA, (n=5) in Clrn2clarinet/+ and 595 ± 67 pA, (n=7) in Clrn2clarinet/clarinet OHCs.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Average peak current-voltage relation for the total K+ current recorded from Clrn2clarinet/+ (P15-16, n=7) and Clrn2clarinet/clarinet (P15-16, n=5) OHCs.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Potassium currents recorded from P22 mature Clrn2clarinet/+ and Clrn2clarinet/clarinet apical-coil IHCs, respectively, using the same voltage protocol described above. Holding potential of -64 mV.",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "Voltage responses from P22 Clrn2clarinet/+ (G) and Clrn2clarinet/clarinet (H,I) IHCs. Note that Ca2+-dependent action potentials could be induced in mature IHCs (I).",
    "ncbi_link": "clarinet: 624224
Clrn2: 624224"
  },
  {
    "caption": "TBH cytotoxicity assay in vivo of the ScAhp1 lysine mutants in yeast. Growth  of yap1Δahp1Δ cells carrying empty vector (ev), wild type peroxiredoxin   gene (AHP1) or indicated cysteine or lysine substitutions was monitored without or with 1 mM TBH. ScAhp14KR: ScAhp1C31S K47/48R K124R K156R; ScAhp15KR: ScAhp1C31S K32R K47/48R K124R K156R.",
    "ncbi_link": "Ahp1: 850799
ahp1: 850799
AHP1: 850799
peroxiredoxin: 850799
yap1: 855005"
  },
  {
    "caption": "In vivo conjugation analyses of ScAhp1  lysine mutants with protein extracts obtained from the indicated yeast  strains expressing HA-URM1. Unconjugated Urm1  and Urm1-Ahp1  conjugates were detected by anti-HA  (top panels) Western blots. Anti-Ahp1 blots  (middle) detect unmodified Ahp1. Anti-Cdc19  (bottom panels) served as loading control. ScAhp14KR: ScAhp1C31S K47/48R K124R K156R; ScAhp15KR: ScAhp1C31S K32R K47/48R K124R K156R.",
    "ncbi_link": "HA: 
Ahp1: 850799
URM1: 854809"
  },
  {
    "caption": "TBH cytotoxicity assay in vivo. Basic growth and the synthetic effect in wild type, ahp1Δ, urm1Δ,  tum1Δ, ncs6Δ, cys3Δ, cys4Δ, cys3Δ urm1Δ, and cys4Δ urm1Δ strains was monitored without or with 1 mM TBH.",
    "ncbi_link": "ahp1: 850799
cys3: 851221
cys4: 853059
ncs6: 852661
tum1: 854425
urm1: 854809"
  },
  {
    "caption": "H2S  production using Biggy agar plates- Wild type, ahp1Δ, urm1Δ, tum1Δ, ncs6Δ, cys3Δ,  cys4Δ,  cys3Δ urm1Δ, and cys4Δ urm1Δ strains were grown on Biggy medium, and H2S  production was recorded",
    "ncbi_link": "ahp1: 850799
cys3: 851221
cys4: 853059
ncs6: 852661
tum1: 854425
urm1: 854809"
  },
  {
    "caption": "In vivo Ahp1 conjugation analyses with protein extracts obtained from the indicated yeast  strains expressing HA-URM1. Unconjugated Urm1  and Urm1-Ahp1  conjugates were detected by anti-HA  (top panels) Western blots. Anti-Ahp1 blots  (middle) detect unmodified Ahp1. Anti-Cdc19  (bottom panels) served as loading control.",
    "ncbi_link": "HA: 
URM1: 854809"
  },
  {
    "caption": "1205Lu cells were transfected, or not, with 2 different siRNA targeted against DRP1 (siDRP1#1 or 2) or an untargeted siRNA (siUT). Top, 48h after transfection, protein extracts were prepared and DRP1 expression was evaluated by western blot. Bottom, 36h post transfection, cells were exposed to 3T3-F442A EV (3T3-EV) and cell motility was tracked by video microscopy (n = 40 cells per group).",
    "ncbi_link": "DRP1: 10059"
  },
  {
    "caption": "TCGA data were analyzed to reveal the effect of high mRNA levels of key FAO enzymes on the overall survival of patients with melanoma. Statistical significance of survival was evaluated with a Log-rank (Mantel-Cox) Test (n=449, 450 and 459 for HADHA, HADHB and ECHS1 respectively).",
    "ncbi_link": "ECHS1: 1892
HADHA: 3030
HADHB: 3032"
  },
  {
    "caption": "(B) Immunoblot analysis of pro- (p31) and cleaved (p17) IL-1β, and pro- (p45) and cleaved (p20) caspase-1 in cytosolic fractions of ASC deficient (Pycard-/-) immortalized murine macrophages that were primed with LPS (200 ng ml−1, for 3h). Fractions were incubated with recombinant ASC specks in the presence of 2, 20 or 200 µg ml−1 of VHHASC or mutVHHASC. One representative of three independent experiments is shown. (C) Quantitative analysis of band densitometry of three independent experiments as shown in B. Data represents the fold change from all conditions (lanes 1- 9) .vs Pycard−/− lysates incubated with ASC specks alone (lane 2). ns, p > 0.05; *, p<0.05; **, p<0.005; ***, p<0.0002, One-way ANOVA, multiple comparison (Dunnet test). Data is displayed as floating bars with the max/min values and mean (thicker band).",
    "ncbi_link": "ASC: 66824
Pycard: 66824"
  },
  {
    "caption": "THP-1 cells expressing a Dox-inducible CRISPR-Cas9 cassette targeting GSDMD gene were treated with 1 µg ml-1 Dox for one or two cycles of 72 h (1x, or 2x respectively). As control, cells were left untreated and cultured in parallel (-). (A) Immunoblot analysis of GSDMD expression following the indicated course of Dox treatment and PMA-differentiation, where indicated. Data is from one representative of two independent experiments.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
GSDMD: 79792"
  },
  {
    "caption": "(D) Representative and summary of immunoblots of lamin B of bone marrow neutrophils from WT and Lmnb1TG mice. Vinculin served as loading control.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(E) Summary analysis of PAF-induced NET formation in mPMNs from WT vs Lmnb1TG mice that were stimulated without or with 10 µM PAF for 3 h, then fixed by 2% PFA and stained by Sytox Green, following by detection with fluorescent microplate reader.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(F) The endpoint analysis of NET-DNA release index was detected by coincubation of primary mouse peritoneal mPMNs from WT and Lmnb1TG mice without (control) or with 10 µM PAF in medium containing 1 μM Sytox Green dye with recording by a microplate reader at the 3 h time point. The NET-DNA release index was reported in comparison to an assigned value of 100% for the total DNA released by neutrophils lysed by 0.5% (v/v) Triton-X-100.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(G,H) Representative images (G) and summary analysis (H) of PAF-induced NET formation in mPMNs from WT vs Lmnb1TG mice that were stimulated without or with 10 µM PAF for 3 h, and stained with both cell permeable SYTO Red and cell impermeable Sytox Green, without fixation. Images were taken by Olympus confocal microscopy, followed by automated quantification of NETs on 5-6 non-overlapping area per well using ImageJ for calculation of % cells with NET formation. (G) Scale bars, 40 μm.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(E) The endpoint analysis of % cells with NET formation was detected with dPMNs that were transfected with plasmids of either wildtype lamin B (WT control), or mutants with single or multiple defined point mutations at PKCα-consensus-phosphorylation sites (S395A, S405A, S408A) of lamin B, and treated for 3 h by 10 μM PAF in medium containing cell-permeable dye SYTO Red (500 nM) for the total cell count, while the cells with NET formation were stained by cell impermeable dye SYTOX Blue (5 μM). Then the images were taken with Olympus confocal microscopy, followed by automated quantification of NETs using ImageJ for quantification of % cells with NET formation. percentage of cells with NET formation by immunofluorescent imaging quantification using ImageJ (E)",
    "ncbi_link": "lamin B: 3930"
  },
  {
    "caption": "(A) Summary and representative immunoblots of PKCα expressions in mouse bone marrow neutrophils from PKCα-/-, PKCα+/-, and their littermate WT (PKCα+/+) mice. Vinculin served as loading control.",
    "ncbi_link": "PKCα: 18750"
  },
  {
    "caption": "(B) Representative immunoblot (IB) detection of the phospho-lamin B (Ser) and total lamin B with lamin B protein purified by immunoprecipitation (IP) with anti-lamin B from mouse peritoneal mPMNs from WT vs PKCα-/- mice, stimulated without or with PAF for 3 h.",
    "ncbi_link": "PKCα: 18750"
  },
  {
    "caption": "(C) Summary analyses of NET formation in peritoneal mPMNs, from WT, PKCα+/-, or PKCα-/- mice, which were treated without or with either 5 µM or 10 µM PAF for 3 h following by 2% PFA fixation and fluorometric microplate analysis.",
    "ncbi_link": "PKCα: 18750"
  },
  {
    "caption": "(D) The endpoint analysis of NET-DNA release index was detected by coincubation of primary mouse peritoneal mPMNs from WT and PKCα-/- mice without (control) or with 10 µM PAF in medium containing 1 μM Sytox Green dye with recording by a microplate reader at the end of the 3 h time point. The NET-DNA release index was reported in comparison to an assigned value of 100% for the total DNA released by neutrophils lysed by 0.5% (v/v) Triton-X-100.",
    "ncbi_link": "PKCα: 18750"
  },
  {
    "caption": "(E, F) (E) Representative and (F) summary analysis of NET formation of mouse peritoneal mPMNs from WT vs PKCα-/- mice stimulated without or with 10 µM PAF for 3 h, and stained with both cell permeable SYTO Red dye and cell impermeable Sytox Green dye, without fixation. Images were taken by Olympus confocal microscopy, followed by automated quantification of NETs on 5-6 non-overlapping area per well using ImageJ for calculation of % cells with NET formation. (E) Scale bars, 50 μm. % cells with NET formation by image analysis using ImageJ (F)",
    "ncbi_link": "PKCα: 18750"
  },
  {
    "caption": "(A,B) representative analysis of confocal fluorescent microscopy images of neutrophils with NET formation in the skin tissue of WT (A) vs Lmnb1TG (B) mice with UVB exposure, in which DNA was stained by DAPI, citrullinated histone H3 was probed by rabbit anti-mouse citrullinated Histone H3, following stained by Alexa Fluor-488 labeled donkey anti-rabbit secondary antibody, while neutrophil surface marker Ly6B was probed by rat anti-mouse Ly6B Ab following stained by Alexa Fluor-647 conjugated goat anti-rat secondary antibody. The images of different staining and their overlays are shown (A,B). The parental neutrophils (stained by neutrophil membrane surface marker Ly6B) and their released extracellular NET structures (co-stained by anti-cit H3 and DAPI) are indicated by red arrows and light blue arrows respectively. The white arrows indicated neutrophils without NET release. Scale bar, 50 µm.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(C) summary analysis of confocal fluorescent microscopy images of neutrophils with NET formation in the skin tissue of WT (A) vs Lmnb1TG (B) mice with UVB exposure, in which DNA was stained by DAPI, citrullinated histone H3 was probed by rabbit anti-mouse citrullinated Histone H3, following stained by Alexa Fluor-488 labeled donkey anti-rabbit secondary antibody, while neutrophil surface marker Ly6B was probed by rat anti-mouse Ly6B Ab following stained by Alexa Fluor-647 conjugated goat anti-rat secondary antibody. The images of different staining and their overlays are shown (A,B). The parental neutrophils (stained by neutrophil membrane surface marker Ly6B) and their released extracellular NET structures (co-stained by anti-cit H3 and DAPI) are indicated by red arrows and light blue arrows respectively. The white arrows indicated neutrophils without NET release. Scale bar, 50 µm.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(D,E) Summary analysis for staining area of neutrophils with NET formation and their exhibition of IL-17A (D) or TNFα (E), in the skin tissue of WT vs Lmnb1TG mice without (sham) or with UVB exposure, by co-staining of Ly6B (stained as described in panels A-C) with IL-17A (D) or TNFα (E) using FITC-conjugated rat anti-mouse IL-17A, or FITC conjugated rat anti-mouse TNFα Abs.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "(G) Effect of ectopic expression of DNA adenine methylase (Dam) protein on TseTBg proteins mediated degradation of plasmid DNA.",
    "ncbi_link": "Dam: 56632906///56633692
DNA adenine methylase: 56632906///56633692"
  },
  {
    "caption": "(E, F) Graph showing the effect of native TsiTBg and HTH or Imm52 domain deleted variant of TsiTBg proteins on Gus reporter gene expression (quantified using 4-methylumbelliferyl ß-D-glucuronide, MUG, as substrate) under the external (pExtTseTBg1/pExtTseTBg2) and internal (pIntTseTBg1/pIntTseTBg2) promoters in E. coli.",
    "ncbi_link": "TseTBg1: 
TseTBg2: 
Gus: 946149"
  },
  {
    "caption": "(A) Interaction of external (pExtTseTBg1) and internal (pIntTseTBg1) promoter DNA fragments of TseTBg1 operon with the TsiTBg1 protein. (B) Interaction of pExtTseTBg1 and pIntTseTBg1 promoter DNA fragments of TseTBg1 operon with the HTH domain deleted variant of TseTBg1 protein (TsiTBg1ΔHTH). (C) Interaction of pExtTseTBg2 and pIntTseTBg2 promoter DNA of TseTBg2 operon with the TsiTBg1 protein. (D) Interaction of control (random) DNA with the TsiTBg1 protein. ",
    "ncbi_link": "TseTBg1: 
TseTBg2: "
  },
  {
    "caption": "Percent body weight of male Prdx4 WT and KO mice over the 72 h course of LPS (4.5 mg/kg BW) or PBS injection (i.p.). Each circle represents a mean of n=7 mice, vertical lines indicate SEM",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Cytokine concentration in Prdx4 WT and KO mice in response to LPS injection. (B) Cxcl1 levels in serum (left) or peritoneal lavage (right) at indicated time points after LPS or PBS injection. (C) TNF-α levels in serum (left) or peritoneal lavage (right) at indicated time points after LPS or PBS injection. (D) IL-1β levels in serum (left) or peritoneal lavage (right) at indicated time points after LPS or PBS injection. Each dot (B-D) represents an individual mouse. Horizontal lines indicate mean.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Percent body weight of male Prdx4 WT and KO mice over the 48 h course of LPS (4.5 mg/kg BW) injection (i.p.) and treatment with IL-1 receptor antagonist (IL-1RA) Anakinra (200 µg/mouse) or control. Arrows indicate time point of Anakinra injection. Each circle represents a mean of n=5 mice, vertical lines indicate SEM.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Serum concentration of Cxcl1, TNF-α and IL-1β in Prdx4 WT and KO mice injected with LPS, LPS and IL-1RA or control. Horizontal lines indicate mean.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Percent body weight of male Prdx4-flox and Prdx4-∆LysMCre mice over the 48 h course of 4.5 mg/kg BW LPS ( i.p.). Each circle represents a mean of n=7 mice, vertical lines indicate SEM.",
    "ncbi_link": "Cre: 2777477
Prdx4: 53381"
  },
  {
    "caption": "Serum concentration of Cxcl1, TNF-α and IL-1β in Prdx4-flox and Prdx4-∆LysMCre mice injected with LPS. Each dot (B, D) represents an individual mouse. Horizontal lines indicate mean.",
    "ncbi_link": "Cre: 2777477
Prdx4: 53381"
  },
  {
    "caption": "Concentration of Cxcl1, TNF-α and IL-1β in the supernatants of Prdx4 WT and KO BMDMs in response to a time course of LPS stimulation (100 ng/ml LPS, time points indicated).",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "IL-1β release of Prdx4 WT and KO BMDMs, untreated or primed for 6 h with LPS (100 ng/ml) and then pulsed for indicated time points with ATP (5 mM).",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Western blot analysis of IL-1β in cell lysates and supernatants of Prdx4 WT and KO BMDMs, primed with LPS (100 ng/ml) and pulsed with ATP (5 mM) for 4 h or left untreated. Dashed line indicates vertical slice.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Immunofluorescence microscopy of ASC speck formation in Prdx4 WT and KO BMDMs in response to Nigericin (10 µg/ml) stimulation for 45 min of LPS-primed cells. Cells were stained with an antibody to ASC and nuclei were counterstained using DAPI. Scale bar indicates 20 µm. ASC speck-positive cells were counted and expressed as percentage of total cells. Bars represent a mean of n=4 mice, vertical lines indicate SD. n.s. not significant (two-tailed t-test).",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Western blot analysis of caspase-1 cleavage in the supernatant of Prdx4 WT and KO BMDMs in response to Nigericin (10 µg/ml) stimulation for 1 h after priming with LPS (100 ng/ml), LPS-priming alone or without stimulation. Whole cell lysates were analyzed for pro-caspase-1 and Gapdh levels.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "IL-1β release in Prdx4 WT and KO BMDMs, untreated or primed for 6 h with LPS (100 ng/ml) and then pulsed for 3 h with ATP (5 mM) or Nigericin (10 µg/ml) or transfected for 3 h with poly (dA:dT) or Flagellin (1 µg/ml each) or treated with transfection agent only.",
    "ncbi_link": "Flagellin: 882052
Prdx4: 53381"
  },
  {
    "caption": "Quantification of cell death by LDH-release in Prdx4 WT and KO BMDMs, untreated or primed for 6 h with LPS (100 ng/ml) and then pulsed for 3 h with ATP (5 mM) or Nigericin (10 µg/ml) or transfected for 3 h with poly (dA:dT) or flagellin (1 µg/ml each) or treated with transfection agent only.",
    "ncbi_link": "flagellin: 882052
Prdx4: 53381"
  },
  {
    "caption": "Foldchange in IL-1β concentration in supernatants of HEK293 cells transfected with plasmids for NLRP3, ASC, IL-1β and caspase-1 WT or Cys-to-Ser mutants C362S or C397S and co-transfected with Prdx4 or control. Cells were stimulated with 2.5 mM ATP for 30 min before analysis.",
    "ncbi_link": "ASC: 51008
caspase-1: 834
IL-1β: 3553
NLRP3: 114548
Prdx4: 10549"
  },
  {
    "caption": "Western blot analysis of non-reducing SDS-PAGE of cell lysates from HEK293 cells transfected with caspase-1 WT, C362S, C397S, or C362S plus C397S mutants and co-transfected with Prdx4-GFP or GFP as control.",
    "ncbi_link": "GFP: 
caspase-1: 834
Prdx4: 10549"
  },
  {
    "caption": "Western blot analysis of co-immunoprecipitation using HA-magnetic beads from cell lysates of HEK293 cells transfected with HA-tagged caspase-1 WT, C362S, C397S, or C362S plus C397S mutants and co-transfected with Prdx4-GFP or GFP as control.",
    "ncbi_link": "GFP: 
HA: 
caspase-1: 834
Prdx4: 53381"
  },
  {
    "caption": "IL-1β concentration in supernatants of HEK293 cells transfected with plasmids for NLRP3, ASC, IL-1β and caspase-1 and co-transfected with Prdx4 WT or Cys-to-Ala mutants C51A, C124A, C245A or DM C124A/C245A or control. Cells were stimulated with 2.5 mM ATP for 30 min before analysis.",
    "ncbi_link": "ASC: 51008
caspase-1: 834
IL-1β: 3553
NLRP3: 114548
Prdx4: 10549"
  },
  {
    "caption": "Western blot analysis of co-immunoprecipitation using HA-magnetic beads from cell lysates of HEK293 cells transfected with HA-tagged caspase-1 WT or control and co-transfected with Prdx4 WT or Cys-to-Ala mutants C51A, C124A, C245A or DM C124A/C245A.",
    "ncbi_link": "HA: 
caspase-1: 834
Prdx4: 10549"
  },
  {
    "caption": "Prdx4 concentration in supernatants of Prdx4 WT or KO BMDMs, primed for 6 h with LPS and pulsed for indicated time points with 5 mM ATP. Each circle represents a mean of n=3 mice, vertical lines indicate SD. **, p < 0.01; n.s. not significant (two-tailed t-test).",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Concentration of Prdx4 in supernatants of Prdx4 WT and KO BMDMs. Cells were primed with LPS (100 ng/ml) for 6 h, followed by pretreatment with 20 µM YVAD or DMSO as control for 30 min and stimulated with 5 mM ATP for 4 h or no further stimulation. Each bar represents a mean of n=3 mice, vertical lines indicate SD. **, p < 0.01; n.s. not significant (two-tailed t-test).",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Western blot analysis of subcellular organelle fractions. OptiPrep density gradient ultracentrifugation was used to fractionate subcellular organelles from Prdx4 WT BMDMs that were primed with LPS (100 ng/ml) for 12 h and stimulated with 5 mM ATP for 4 h.",
    "ncbi_link": "Prdx4: 53381"
  },
  {
    "caption": "Cxcl1 concentration in supernatants of caspase-1-deficient BMDMs stimulated with EVs from LPS, LPS and ATP or control-treated Prdx4 WT or KO BMDMs, as well as caspase-1-deficient BMDMs pre-treated with Anakinra and stimulated with EVs from LPS and ATP-treated Prdx4 WT or KO BMDMs. Each bar represents a mean of n=3 biological with 2 technical replicates, vertical lines indicate SD.",
    "ncbi_link": "caspase-1: 834
Prdx4: 53381"
  },
  {
    "caption": "Serum Cxcl1 in C57Bl6/N mice injected with either PBS or EVs from LPS and ATP or control-treated Prdx4 WT or KO or ASC KO BMDMs. Each dot represents an individual mouse. Horizontal lines indicate mean.",
    "ncbi_link": "Prdx4: 53381
ASC: 66824"
  },
  {
    "caption": "(B) Volcano plot of 8,701 mRNA isoforms from 2,931 genes with multiple isoforms. X-axis indicates a difference in percentage of each mRNA isoform within the gene (Δ%smg-2-N2). Y-axis indicates -log10 of p-value in Fisher's exact tests. Blue symbols indicate 219 mRNA isoforms significantly depleted from the smg-2 mutant (p<0.05, Δ%smg-2-N2<-10). Red symbols indicate 420 isoforms significantly enriched in the smg-2 mutant (p<0.05, Δ%smg-2-N2>10).",
    "ncbi_link": "smg-2: 171696"
  },
  {
    "caption": "(C, D) Length distribution of 3'UTRs (C) and proportions of putative PTC-containing isoforms (D) in 10,136 mRNA isoforms detected in N2 and/or smg-2 (All), the 219 isoforms depleted from and the 420 isoforms enriched in the smg-2 mutant.",
    "ncbi_link": "smg-2: 171696"
  },
  {
    "caption": "(B) Alternative splicing of sams-3, sams-4 and sams-5 in unfed and fed worms without or with a protein synthesis inhibitor emetine. Synchronized L1 larvae of an NMD-deficient strain KH1668: smg-2 (yb979) (lanes 1-3) and a wild-type strain N2 (lanes 4-6) were incubated in S-complete medium alone (lanes 1, 4), with a standard E. coli strain OP50 (OD600=10.0) (lanes 2, 5) or OP50 supplemented with 10 mg/ml emetine (lanes 3, 6) for 3 hours at 20°C. Total RNAs were extracted from whole animals and subjected to semi-quantitative RT-PCR, whose products were analyzed by capillary electrophoresis. Representative gel-like presentation is indicated (n=3). Schematic structure of each PCR product is indicated on the right. Open reading frames (ORFs) for full-length and truncated proteins are in orange and cyan, respectively. rpl-12 was used as an unaffected control.",
    "ncbi_link": "rpl-12: 178279
sams-3: 177355
sams-4: 177354
sams-5: 177389
smg-2 : 171696"
  },
  {
    "caption": "(A) Alternative splicing of sams-3, sams-4 and sams-5 in smg-2 (yb979) and smg-2 (yb979); sams-5 (gk147); sams-1 (ok2946) mutants. Synchronized L1 larvae of each strain were incubated in S-complete medium alone (lanes 1 and 5), with OP50 (OD600=10.0) (lanes 2 and 6) and with OP50 supplemented with 25 mM L-Met (lanes 3 and 7) or 25 mM cycloleucine (cLeu) (lanes 4 and 8) for 3 hours at 20°C. The splicing patterns were analyzed and presented as in Figure 2B (n=3).",
    "ncbi_link": "sams-1: 181370
sams-3: 177355
sams-4: 177354
sams-5: 177389
smg-2: 171696"
  },
  {
    "caption": "(B, C) Western blot analysis of SAMS-1, SAMS-3 and SAMS-4 during larval development in the smg-2 (yb979) (B) and wild-type (C) backgrounds. Genotypes of the worms are smg-2 (w) and smg-2; sams-5; sams-1 (s) in (B) and wild-type (w) and sams-1 (s) in (C). Synchronized L1 larvae of each strain were incubated with OP50 at 20°C and subjected to Western blot analysis at indicated time points. Anti-β-tubulin (B) or coomassie brilliant blue (CBB) staining (C) was used as a loading control. Specificity of the antibodies is confirmed in Appendix Figure S12. Note that upregulation of SAMS-1 protein in the wild type during larval development in (C) is consistent with feeding-induced upregulation of sams-1 mRNA in Figure EV3D.",
    "ncbi_link": "sams-1: 181370
sams-5: 177389
smg-2: 171696"
  },
  {
    "caption": "(C) Alternative splicing of sams-3, sams-4 and sams-5 in smg-2 (yb979) and smg-2 (yb979); mett-10 (ok2204) mutants. Synchronized L1 larvae of each strain were incubated in S-complete medium alone (lanes 1 and 3) or with OP50 (lanes 2 and 4) for 3 hours at 20°C and the splicing patterns were analyzed and presented as in Figure 2B.",
    "ncbi_link": "mett-10: 191526
sams-3: 177355
sams-4: 177354
sams-5: 177389
smg-2: 171696"
  },
  {
    "caption": "(A) Mass chromatograms of RNA fragments to detect m6A (top) or unmodified A (bottom) after in vitro incubation of 127-nt sams-3/sams-4 pre-mRNA (sequence available in Fig EV2) with recombinant full-length METT-10 protein in the presence (left) or absence (right) of 1 mM SAM. The sequence, m/z value, and charge state for each fragment are indicated on the right. Asterisks indicate non-specific signals.",
    "ncbi_link": "sams-3: 177355
sams-4: 177354"
  },
  {
    "caption": "A, B) m6A-IP specifically enriched sams mRNA isoforms that retain the AG dinucleotide at the distal/productive 3'SS. (A) Representative gel-like images (n=3) of semi-quantitative RT-PCR analysis of sams-3, sams-4 and sams-5 in input and immunoprecipitated (IP) RNAs from the smg-2 (yb979) mutant. The splicing patterns were analyzed and presented as in Figure 2B. (B) Relative enrichment of total and each of mRNA isoforms compared to eef-1A.1 mRNA by RT-qPCR. Error bars indicate standard error of mean (n=3). ( ",
    "ncbi_link": "eef-1A.1: 175975
sams-3: 177355
sams-4: 177354
sams-5: 177389
smg-2: 171696"
  },
  {
    "caption": "C) Examples of normalized Nanopore currents for unmodified and m6A-modified in-vitro transcribed sams-3/sams-4 RNAs at nucleotide positions -4 through +4 relevant to the m6A site. One hundred reads are lotted for each. Color codes are indicated. (D) Distribution of mean (top) and standard deviation (bottom) of normalized Nanopore currents at nucleotide positions -4 through +4 relevant to the m6A site for 5,000 of the unmodified and 2,680 of the m6A-modified sams-3/sams-4 RNAs and 85 of an endogenous sams-3 mRNA isoform E2/E3L. Color codes are indicated. Central bands represent the median, boxes represent the 25th and 75th percentiles, and whiskers represent the lowest and highest values. A red line at position 0 in the top panel indicates a cut-off line (mean current = 1.7557) that discriminates between the unmodified and m6A-modified sams-3/sams-4 RNAs with accuracies of 64.58% for both. ( ",
    "ncbi_link": "sams-3: 177355
sams-4: 177354"
  },
  {
    "caption": "C, D TNT formation (marked by black triangles and white arrowheads) was imaged in control and shM2 H1299 (C) and shM2 A549  (D) cells by confocal microscopy. Scale bar: 60 μm. Boxed areas are enlarged and shown at the bottom of the corresponding images. E, F Quantification of the percentage of cells forming TNTs in control and shM2 H1299 (E) and shM2 A549  (F) cells. 13  images per group (E) and 10 per group (F) were captured for quantification. Three independent experiments were conducted. G Data information: data were analyzed by one-way ANOVA with Bonferroni post-test and shown as mean ±SEM; *** P < 0.001. Three independent experiments were performed",
    "ncbi_link": "M2: 9645"
  },
  {
    "caption": "H,I H1299 cells stably expressing the Ctr or GFP-M2 were cultured in the presence of 20 μM 2-DG for 24 h to induce TNT formation. TNTs were imaged by confocal microscopy (A) and the percentage of cells forming TNTs was quantified (B). n=21, 20 and 19 images were captured from Ctr, GFP-M2#1 and GFP-M2#2, respectively. Three independent experiments were performed. Scale bar: 60 μm. Data information: data were analyzed by one-way ANOVA with Bonferroni post-test and shown as mean ±SEM; *** P < 0.001. Three independent experiments were performed",
    "ncbi_link": "GFP: 
M2: 9645"
  },
  {
    "caption": "A Time-lapse microscopic images showing that H1299 shCtr or shM2 cells stably expressing Mito-GFP were connected by TNTs containing mitochondria. Cells were seeded in  collagen-coated dishes and cultured for 24 h before  time-lapse life cell  images were acquired by confocal microscopy (also see Movies EV1 and EV2). Fluorescent images (with bright field) at different time points show the mitochondria moving along the TNT and entering in one of the two connected cells. Scale bar: 20 μm. The moving mitochondria are marked by the white arrows. Boxed areas (shCtr in yellow dotted boxes; shM2 in red dotted boxes) are enlarged and shown in the middle panel. B Confocal microscopic images of control and shM2 H1299 cells following immunofluorescence staining with anti-Tom20 antibody (green) and staining  using phalloidin (red). The white arrows marked TNTs, whereas the white triangles marked mitochondria inside TNTs. Scale bar: 25 μm. C Data information: nuclei were stained with Hoechst 33342 (blue).",
    "ncbi_link": "GFP: 
M2: 9645"
  },
  {
    "caption": "C Quantification of TNTs containing mitochondria in shCtr and shM2 H1299 cells. The percentage of TNTs containing  mitochondria was determined. n=168, 187 and 192 for shCtr, shM2#1 and shM2#2 groups, respectively; three independent experiments. Data information: data were analyzed using FlowJo analysis software. When  co-cultured through the filter in transwells, only 0.01% or f",
    "ncbi_link": "M2: 9645"
  },
  {
    "caption": "E Representative flow cytometry plot of shCtr and shM2 cells following co-culture for 2 days. Experiments were conducted under three conditions: co-cultured in direct contact in normal glucose medium or in  galactose medium or co-cultured through a filter.",
    "ncbi_link": "M2: 9645"
  },
  {
    "caption": "F The percentage of mCherry-expressing recipient cells containing Mito-GFP was quantified. Twenty thousand events were acquired for each condition and data were analyzed using FlowJo analysis software. When co-cultured through the filter in transwells, only 0.01% or fewer recipient cells contained  Mito-GFP, and this group is not included in the graph to avoid an overcrowded figure. Three independent experiments were conducted. Data information: data were analyzed using FlowJo analysis software. When  co-cultured through the filter in transwells, only 0.01% or f",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A Down-regulating MICAL2PV promotes mitochondrial infiltration into the cortical cytoskeleton. Control and shM2 H1299 cells were subjected to immunofluorescence staining  with anti-Tom20  antibody (green) and staining using  phalloidin (red). Scale bar: 25 μm. Data information:  nuclei were stained with Hoechst 33342 (blue).",
    "ncbi_link": "M2: 9645
MICAL2PV: 9645"
  },
  {
    "caption": "C Down-regulating MICAL2PV enhances the mitochondrial localization of Miro1, Miro2 and KIF5B. Mitochondria were purified from control and shM2 H1299 cells and subjected to Western blotting. The purity of the mitochondrial fraction was confirmed by detection of mitochondrial ATP5B and the absence of the  cytoplasmic β-tubulin protein.",
    "ncbi_link": "M2: 9645
MICAL2PV: 9645"
  },
  {
    "caption": "E MICAL2PV interacts with the C-terminal domain of Miro2 containing the transmembrane region. H1299 cells were co-transfected with plasmids encoding  Flag-MICAL2PV and Myc-tagged  Miro2 mutants as indicated. Following transfection, cells were lysed for immunoprecipitation using the anti-Flag antibody and Western blotting. Please note the  Myc-Miro2 (410-618) protein band in lane 4 migrated as a faint band, slightly faster than the IgG light chain.",
    "ncbi_link": "Flag: 
Myc: 
MICAL2PV: 9645
Miro2: 89941"
  },
  {
    "caption": "F MICAL2PV inhibits the mitochondrial localization of  Miro2 and mitochondrial  infiltration. H1299 cells were co-transfected with Myc-tagged  Miro2 and GFP-tagged MCAL2PV (GFP-M2) or control vector. Following transfection, cells were fixed and  stained  with anti-Tom20 (red) and anti-Myc antibodies (magenta). Confocal microscopic images were taken under the same objective and the same microscope settings. In cells co-expressing the GFP vector and Myc-Miro2 (upper panels), most of Miro2 signals (magenta) are co-colocalized with mitochondria (red Tom20  signals). However, a significant fraction of Miro2 signals is not colocalized with mitochondria in cells co-expressing GFP-M2 and Myc-Miro2  (marked by the yellow arrowheads).  Mitochondria in cells expressing GFP-M2 show the  perinuclear distribution pattern, whereas  mitochondria in cells transfected by Myc-Miro2 without GFP-M2 (marked by the yellow stars) exhibit an infiltration pattern into the  cortical cytoplasm. Scale bar: 20 μm.",
    "ncbi_link": "GFP: 
Myc: 
M2: 9645
MCAL2PV: 9645
MICAL2PV: 9645
Miro2: 89941"
  },
  {
    "caption": "A Control and shM2 H1299 cells were transfected with control siRNA or siRNAs targeting  Miro2. Following transfection, cells were stained with anti-Tom20 antibody (green) and  phalloidin (red). Confocal microscopic images are shown. Scale bar: 20 μm. Data information: nuclei were stained  with Hoechst 33342 (blue).",
    "ncbi_link": "M2: 9645
Miro2: 89941"
  },
  {
    "caption": "F Down-regulating  Miro2 inhibits mitochondrial transport in shM2 cells. Mito-GFP labelled control and shM2 H1299 cells were transfected with control siRNA or siRNAs targeting  Miro2. These cells were then co-cultured with mCherry labelled recipient cells and analyzed by flow cytometry The percentage of  mCherry recipient cells containing Mito-GFP was quantified. Twenty thousand events were analyzed for each condition Data information: Data were analyzed using two-way ANOVA with Bonferroni post-test and presented as mean ± SEM; * P < 0.05, *** P < 0.01, *** P < 0.001, ns, not significant. Three independent experiments were conducted.",
    "ncbi_link": "GFP: 
M2: 9645
Miro2: 89941"
  },
  {
    "caption": "A Stable H1299 cells (shCtr or shM2) were treated by 5-FU (50 μM, 24 h) and then cultured alone or co-cultured with non-drug treated vehicle-treated cells stably expressing mito-mCherry in the absence or presence of Cyto B  (500 nM, 24 h). The percentage of dead cells in each group was quantified. Three independent experiments were conducted. Data information: data were analyzed using two-way ANOVA with Bonferroni post-test and shown as mean ± SEM; * P < 0.05, ** P < 0.01, *** P < 0.001, ns, not significant.",
    "ncbi_link": "mCherry: 
M2: 9645"
  },
  {
    "caption": "D MICAL2PV mutants containing the MO domain are active in depolymerizing F-actin. Following transfection of plasmids expressing different HA-MICAL2PV mutants (#1, #2, or #4) into shM2 cells, confocal microscopy was performed following staining with phalloidin (red) and anti-HA antibody (green).  F-actin signals were reduced in cells expressing different mutants (HA-positive green cells marked by dashed lines). Scale bar: 20 μm. Data information: nuclei were stained with Hoechst 33342 (blue).",
    "ncbi_link": "HA: 
M2: 9645
MICAL2PV: 9645"
  },
  {
    "caption": "G, H The  MICAL2PV mutant containing an inactive MO domain does not inhibited TNT formation. Stable shM2 H1299 (G) or A549 (H) cells were transfected with plasmids expressing the MICAL2PV  mutant in which the MO domain was inactivated by mutations in the FAD binding site (MOmut: amino acid residues 93-98 GxGxxG mutated to WxWxxW) or the control vector (Ctr). Following transfection, Western blotting and quantification of TNT formation were carried out as in panel E. 10 images were captured for quantification in each group. Three independent experiments were performed. Data information: Data were analyzed using a one-way ANOVA with Bonferroni post-test and shown as mean ± SEM; * P < 0.05, ** P < 0.01, *** P < 0.001, ns, not significant.",
    "ncbi_link": "M2: 9645
MICAL2PV: 9645"
  },
  {
    "caption": "Live cell microscopy  of  U-2 OS-TetO cells expressing rTetR-GFP   (ctrl), or rTetR-GFP-Kin14VIb  (Kin14VIb) (B) Representative stills showing the most frequently observed metaphase localization  and daughter nuclei  distribution of the duplicated TetO locus (white arrowheads). Chromatin  was visualized through expression  of H2B-mCherry, GFP  depicts the TetO locus. Due to the presence of a predicted NES sequence in Kin14VIb, the TetO locus only becomes visible at NEB   in Kin14VIb-expressing cells. Time  = h:min, scale bar = 5 µm. Schemes illustrating the metaphase localization  of the TetO locus and its subsequent distribution over daughter nuclei  are shown on the right.",
    "ncbi_link": "GFP: 
Kin14VIb: 112281002"
  },
  {
    "caption": "(C) Quantification of the fraction of ctrl or Kin14VIb-expressing cells with the TetO locus observed outside the metaphase  plate (TetO out). (D) Deconstruction of (C). Fraction of cells with the indicated orientation of the duplicated TetO locus and TetO chromosome. Data information: Bars represent the mean of 2 biological replicates, while dark- and light-colored dots represent the values of each experiment. (C, D): N ≥ 29 cells per condition, per experiment, ****P<0.0001; Fisher's exact test.",
    "ncbi_link": "Kin14VIb: 112281002"
  },
  {
    "caption": "E. Quantification of the number of cells with Mad1-positive KTs  nearby the TetO locus. In case the KTs  of the TetO chromosome  were aligned, we scored whether KTs  in the vicinity of the TetO locus were Mad1+. In case the KTs of the TetO chromosome  could be distinguished in rTetR-GFP-Kin14VIb-expressing cells (with either orthogonal or parallel oriented KTs), we scored if at least one of the KTs  was Mad1+. Data information: Bars represent the mean of 2 biological replicates, while dark- and light-colored dots represent the values of each experiment. (E): N ≥27 cells per condition, per experiment, (ns) not significant; Fisher's exact test.",
    "ncbi_link": "GFP: 
Kin14VIb: 112281002"
  },
  {
    "caption": "A-D (A, C) Frequencies of the different types of segregation errors observed during anaphase  (A) and late anaphase/telophase  (C). Schemes illustrating the observed types of anaphase  errors are shown on the right of (A). Cells within the main TetO locus distribution categories in control (1-1), and Kin14VIb  (2-0) conditions were scored (see also Fig EV1A). The majority of Kin14VIb-expressing anaphases  display at least one stretched arm (CENP-C in line with TetO locus at the pole) or a bridge in line with the TetO locus at the pole  (\"stretched arm or bridge in line\"), some of them with additional bridges (+). (B, D) IF  images for  CENP-C, GFP, H3S10ph of  U-2 OS TetO cells in anaphase  (B) and late anaphase  or telophase  (D), expressing either rTetR-GFP  or rTetR-GFP-Kin14VIb. Images (maximum intensity projections) represent the most frequently observed anaphase  and telophase  errors in cells with either a 1-1 (majority of events in ctrl), or 2-0 (majority of events in Kin14VIb) TetO locus distribution. Scale bar = 5 µm. Yellow arrowheads indicate TetO locus, red arrowheads CENP-C. Data information: (A, C): Means ± S.E.M. of 3 biological replicates are shown. Dots represent the values of each experiment. N= 41-89 cells per condition, per experiment ****P<0.0001, (ns) not significant; Fisher's exact test. (B, D): for optimal visibility of the TetO foci, the brightness and contrast of all channels were linearly adjusted for individual cells.",
    "ncbi_link": "GFP: 
Kin14VIb: 112281002"
  },
  {
    "caption": "A. Representative images of U-2 OS TetO anaphases/telophases  expressing rTetR-GFP  or rTetR-GFP-Kin14VIb  with FISH-marked centromeres  of chromosome 1 (chr1-CEN). White and yellow arrowheads: chr1-CEN  segregated into the main masses of segregating chromosomes; red arrowheads: chr1-CEN FISH  signal fragmented or splitted in a bridge  (bridging); chr1-CEN  lagging  between the two main masses of segregating chromosomes  (lagging); chr1-CEN  late arrival (late-equal: one CEN  focus in but near the edge of a separated chromosome  mass and connected to a bridge). For clarity, the maximum intensity projection of a subset of z stacks (6-12/64) is shown. Scale bar = 5 µm. B. Frequency of the different types of errors observed in A. The mean (bars) and individual values (dots) of 2 independent experiments are shown. Data information: In (A), for optimal visibility of the chr1-CEN FISH  foci, the brightness and contrast were linearly adjusted for individual cells. (B): n ≥ 45 cells per condition, per experiment. Bars represent the mean of 2 biological replicates, while dark- and light-colored dots represent the values of each experiment. * P<0.05, (ns) not significant. Fisher's exact test.",
    "ncbi_link": "GFP: 
Kin14VIb: 112281002"
  },
  {
    "caption": "C. IF  for Cas9  and CENP-C of metaphases  of RPE1-dCas9-Kin14VIb  cells transduced with Chr1-telo  sgRNA in the presence or absence of 500 nM rapalog. The Chr1-telo  loci (Cas9  foci, white arrowheads) are aligned on the metaphase  plate in control condition (- rapalog), while the loci are facing either a single or opposite poles  after rapalog  addition to induce Kin14VIb binding  to dCas9. Scale bar = 5 µm. For clarity, the maximum intensity projection of a subset of z stacks (18-50/100) is shown. Data information: (C for optimal visibility of the Chr1-telo  foci, the brightness and contrast of all channels were linearly adjusted for individual cells.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "D,  Live cell microscopy   of asynchronously growing RPE1-dCas9-Kin14VIb  cells transduced with Chr1-telo  sgRNA in the presence or absence of 500 nM rapalog  to induce kinesin binding  to the subtelomeric  locus. (D) Stills showing the most frequently observed metaphase localization  and daughter cell  distribution (white arrowheads) of the duplicated Chr1-telo  loci. SiR-DNA  was used to visualize the DNA, GFP  depicts the Chr1-telo  loci. Time  (h:min). Scale bar = 5 µm. Note that in the upper panel, the cell was already in mitosis when imaging started (t =0:00). Data information: (D, Cells were derived from three independent imaging experiments. N = 23 cells (- rapalog), n = 41 cells (+ rapalog). Sp = same pole, op = opposite pole, ss = same sisters. D): for optimal visibility of the Chr1-telo  foci, the brightness and contrast of all channels were linearly adjusted for individual cells.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "B,  Live cell microscopy  of asynchronously growing RPE1-dCas9-Kin14VIb  cells transduced with Chr9-cen  sgRNA and plus/minus rapalog  to induce kinesin binding  to the pericentromeric  locus (Movies S4-S8). (B) Stills of the most frequently observed metaphase  orientations and daughter cell distributions of the duplicated Chr9-cen  loci (white arrowheads) are shown.  SiR-DNA was used to visualize the DNA, GFP  depicts the Chr9-cen  loci. Time  (h:min). Scale bar = 5 µm. Data information: Cells were derived from two independent imaging experiments.. In (B), for optimal visibility of the Chr9-cen  foci, the brightness and contrast of all channels were linearly adjusted for individual cells. See Movies EV4- S8 for equally adjusted corresponding examples.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "D. Time  between  nuclear envelop break down (NEB) and anaphase  onset in the presence (Kin14VIb  bound to dCas9) or absence (Kin14VIb  expressed, but not bound to dCas9) of rapalog. Data information: Cells were derived from two independent imaging  experiments.. (D): Mean and S.D. are shown.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "A. Representative IF  images of RPE1-dCas9-Kin14VIb  cells, showing the localization  of the Chr9-cen  loci in metaphase  in the absence or presence or rapalog. Magnifications of the white boxed regions (each region showing one Chr9-cen  locus) are shown in the corners (scale bars = 2 µm). The fraction of cells with Chr9  mis-aligned and CENP-C near the locus (Cas9) is indicated below the image. For clarity, the maximum intensity projection of a subset of z stacks in which the Chr9-cen  loci are in focus (2-10/100) is shown. B. Frequency of the observed metaphase localizations  of the Chr9-cen  loci as shown in (A). Data information: In all cases, bars represent the mean of 2 independent experiments, while dark- and light-colored dots represent the values of each experiment. (B): **** P<0.0001, Fisher's exact test. N ≥ 31 cells per condition, per experiment. (A, For optimal visibility of the Chr9-cen  foci the brightness and contrast of all channels were linearly adjusted for individual cells.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "C. Representative IF   images of RPE1-dCas9-Kin14VIb  cells, showing the segregation and distribution of Chr9-cen  loci in anaphase  (white arrowheads). Red arrowheads indicate H3S10ph-positive chromatin bridges. For clarity, the maximum intensity projection of a subset of z stacks in which the chr9-cen  loci are in focus (30-62/100) is shown. Scale bar = 2 µm. Data information: C): For optimal visibility of the Chr9-cen   foci H3S10ph-positive  chromatin bridges, the brightness and contrast of all channels were linearly adjusted for individual cells.",
    "ncbi_link": "Cas9: 69900935
Kin14VIb: 112281002"
  },
  {
    "caption": "(B) The region of FYCO1 between aa 1,276 and 1,294 is essential and sufficient for the interaction with LC3B. GST or GST-LC3B were incubated with [S35]methionine-labeled deletion mutants of FYCO1 and processed as in Fig. 1 C.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(C) LIR is essential for colocalization of FYCO1 with LC3B in HeLa cells. HeLa cells expressing the indicated constructs were imaged by confocal microscopy. Insets show an enlarged field of interest.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(D) Both N- and C-terminal domains of LC3B are needed for efficient interaction with FYCO1. GST, GST-LC3B, or its deletion mutants were incubated with [S35]methionine-labeled myc-FYCO1 and processed as in Fig. 1 C. ARG, autoradiography; CB, Coomassie blue.",
    "ncbi_link": "LC3B: 81631"
  },
  {
    "caption": "(C) FYCO1 can self-interact in a CC-dependent manner. Full-length GFP-FYCO1 was cotranscribed and cotranslated with the indicated deletion mutants of myc-tagged FYCO1 in rabbit reticulocyte lysate. S35-labeled FYCO1 complexes were immunoprecipitated with anti-myc antibody, separated by SDS-PAGE, and visualized by autoradiography. IP, immunoprecipitation.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(B) FYCO1990-1,233 is the smallest FYVE domain-containing deletion mutant of FYCO1 that can efficiently interact with the full-length FYCO1. Full-length myc-FYCO1 was cotranscribed and cotranslated with the indicated deletion mutants of GFP-tagged FYCO1 in rabbitreticulocyte lysate. S35-labeled FYCO1 complexes were immunoprecipitated with anti-SDS-PAGE antibody, separated by SDS-PAGE, and visualized by autoradiography. IP, immunoprecipitation.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(A) Rab7Q67L recruits FYCO11,038-1,233 and FYCO11,091-1,233 but not FYCO11,156-1,233 to the cytosolic vesicles. HeLa cells transfected with GFP-FYCO11,038-1,233 (top), GFP-FYCO11,091-1,233 (bottom), or GFP-FYCO11,156-1,233 (middle right) with or without mCherry-Rab7Q67L were imaged 24 h after transfection. The graph shows the relative number of cells ± SD with GFP-FYCO11,038-1,233 recruited to intracellular membranes without and with cotransfected mCherry-Rab7Q67L.",
    "ncbi_link": "FYCO1: 79443
Rab7: 338382///7879"
  },
  {
    "caption": "(B) Rab7Q67L recruits the 2xFYVEFYCO1 construct containing a short CC region in front of the first FYVE domain (FYCO11,091-1,233+1,156-1,233) but not a 2xFYVE alone to the perinuclear vesicles. HeLa cells transfected with GFP-FYCO11,091-1,233+1,156-1,233 or GFP-FYCO11,156-1,233+1,156-1,233 with or without mCherry-Rab7Q67L were imaged 24 h after transfection.",
    "ncbi_link": "FYCO1: 79443
Rab7: 338382///7879"
  },
  {
    "caption": "(D) Leucine-1151 and tryptophan-1152 are important for the recruitment of FYCO1 to Rab7-containing vesicles. HeLa cells transfected with GFP-FYCO1990-1,233L1151A/W1152A with or without mCherry-Rab7Q67L were imaged 24 h after transfection. (B and D) Insets show an enlarged field of interest.",
    "ncbi_link": "FYCO1: 79443
Rab7: 338382///7879"
  },
  {
    "caption": "(D) Full-length FYCO1 but not the FYCO1 lacking aa 555-1,136 can redistribute Rab7 and ORP1L to the cell periphery. HeLa cells were transfected with the indicated constructs and stained with DRAQ5.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(E) The region of FYCO1 between aa 675 and 771 is essential for the MT plus end translocation of FYCO1-decorated structures. HeLa cells were imaged 24 h after transfection with the indicated constructs.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(B) Representative images of HeLa cells with or without the perinuclear clusters of GFP-LC3-positive vesicles (right) and quantification of the number of cells with this phenotype 48 h after transient transfection with siRNAs against FYCO1 (left). Error bars represent SDs based on three independent experiments.",
    "ncbi_link": "FYCO1: 79443"
  },
  {
    "caption": "(A) Raji-Env cells were subcloned to obtain cell lines expressing increasing amounts of Env. Env surface levels were determined by the binding of 10-1074 and measured by flow cytometry. One representative experiment is shown.",
    "ncbi_link": "Env: 155971"
  },
  {
    "caption": "(D) HIV- or HIV∆Vpu-infected CD4 T cells (strain NLAD8) were subjected to antibody binding with indicated antibodies and surface levels were determined by flow cytometry (left panel). The staining obtained with mGO53 was similar to the background signal observed on unstained cells. Infected cells were cultured with the indicated antibodies and NHS for 24h and the C3 surface levels on infected (Gag+) cells were determined by flow cytometry (right panel). One representative experiment is shown.",
    "ncbi_link": "Vpu: 155945"
  },
  {
    "caption": "(A) Primary CD4 T cells were nucleofected with a control (CRISPR Control) or anti-CD59 (CRISPR CD59) guide RNA/Cas9 complex. CD59 surface levels were analyzed by flow cytometry 7 days after nucleofection. Isotype control (grey) and CD59 stainings (blue). One representative experiment is shown on the left. Numbers indicate the % of CD59+ cells (middle) or the MFI of staining in CD59- cells (Right). Each dot represents a single donor of CD4 T cells. n=6 donors of CD4 T cells.",
    "ncbi_link": "Cas9: 57852564
CD59: 966"
  },
  {
    "caption": "(B) NLAD8∆Vpu-infected CD59 KO primary CD4 T cells were cultured with indicated antibodies and NHS or HIHS for 24h. Numbers indicate the percentage of infected (Gag+) cells. One representative experiment is shown.",
    "ncbi_link": "CD59: 966
Vpu: 155945"
  },
  {
    "caption": "(C) CD59-KO (CRISPR CD59) or control (CRISPR Control) CD4 T cells infected with HIV WT (left) or HIVΔVpu (right) (strain NLAD8) were cultured with the indicated antibody, and NHS or HIHS for 24h. The % of CDC was calculated as the % of disappearance of Gag+ cells after culture with NHS compared to HIHS. Each dot represents a single donor of CD4 T cells. n= at least 6 donors of CD4 T cells.",
    "ncbi_link": "CD59: 966
Vpu: 155945"
  },
  {
    "caption": "(C) Frequency of live HIV-1-infected cells (NLAD8 WT or ΔVpu strain) 6 days after incubation with the indicated antibodies, and with NHS or HIHS. Each donor of CD4 T cells is represented by a different symbol. n=8 donors of CD4 T cells.",
    "ncbi_link": "Vpu: 155945"
  },
  {
    "caption": "(D) Elimination of HIV-1-infected cells (strain NLAD8 WT or ΔVpu) over culture with the indicated antibody (E430G), and NHS or HIHS. The frequency of % infected (Gag+) cells is determinined by flow cytometry. The mean relative percentage of infected cells compared to the HIHS condition is depicted. n=6-8 donors of CD4 T cells.",
    "ncbi_link": "Vpu: 155945"
  },
  {
    "caption": "(C) CD4 T cells not infected (NI) or infected with WT, ∆Nef, ∆Vpu or ∆Nef∆Vpu HIV-1 (strain CH058) were incubated with the serum of HIV-1-infected ART-treated individuals (sKB104 or sKB105, dilution 1:1000). The levels of IgG binding on infected (Gag+) cells were analyzed by flow cytometry. One representative experiment is shown on the left. On the right, results are expressed as MFI of staining. Each dot represents a single donor of CD4 T cells. n=6 donors of CD4 T cells. Error bars indicate SEM. *P<0.05, Wilcoxon test. Only significant comparisons are depicted.",
    "ncbi_link": "Nef: 156110
Vpu: 155945"
  },
  {
    "caption": "(D) Primary CD4 T cells either not infected (NI) or infected with WT, ∆Nef, ∆Vpu or ∆Nef∆Vpu HIV-1 (strain CH058) were incubated with 50% NHS from a healthy donor and serum of HIV-1-infected ART-treated individuals (sKB104 or sKB105, dilution 1:100). The levels of C3 deposition on infected (Gag+) cells were analyzed by flow cytometry. One representative experiment is shown (left panel). Results are expressed as MFI of staining (right panel). Each dot represents a single donor of CD4 T cells. n=6 donors of CD4 T cells.",
    "ncbi_link": "Nef: 156110
Vpu: 155945"
  },
  {
    "caption": "(E) Correlation between patients' sera (sK104 and sKB105) antibody binding and C3 deposition on CD4 T cells either mock-infected or infected with WT, ∆Nef, ∆Vpu or ∆Nef∆Vpu HIV-1 (strain CH058). Each dot is the mean of 6 donors of CD4 T cells. Correlation was analyzed by Spearman correlation. Correlation coefficient (r) and p-value are indicated.",
    "ncbi_link": "Nef: 156110
Vpu: 155945"
  },
  {
    "caption": "Primary brown adipocytes were transfected with MPC1 siRNA (MPC1 KD) or Scramble RNA (Scramble). (C) Representative Western Blot analysis of MPC1, MPC2 and actin. (D) Quantification of MPC1 and MPC2 expression normalized to actin from Western Blots in (C) from n=3 individual experiments.",
    "ncbi_link": "MPC1: 55951"
  },
  {
    "caption": "Primary brown adipocytes were transfected with MPC1 siRNA (MPC1 KD) or Scramble RNA (Scramble). (E) mRNA levels of MPC1 and MPC2 from n=3 individual experiments.",
    "ncbi_link": "MPC1: 55951
MPC2: 70456"
  },
  {
    "caption": "Primary brown adipocytes were transfected with MPC1 siRNA (MPC1 KD) or Scramble RNA (Scramble). (F) Representative OCR traces of differentiated primary brown adipocytes averaging 6 technical replicates. OCR were measured in respirometry media supplemented with 5 mM glucose and 3 mM glutamine. Norepinephrine (NE; 1 µM), oligomycin A (Oligo; 4 µM), etomoxir (Eto; 40 µM) and antimycin A (AA; 4 µM) were injected where indicated. (G) Quantification of basal, NE-stimulated and Eto-sensitive OCR as shown in (F) from n=7 individual experiments. Data were normalized to Scramble RNA for each individual experiment. (H) Quantification of basal OCR in response to 100 nM UK5099 treatment in Scramble RNA of MPC1 siRNA transfected cells from n=5 individual experiments. Data were normalized to vehicle for each experiment.",
    "ncbi_link": "MPC1: 55951"
  },
  {
    "caption": "(C-E) Effect OGC1 downregulation on UK5099-induced energy expenditure. Primary brown adipocytes were transduced with Scramble RNA (Scramble) or shOGC1 (OGC1 KD) adenovirus. Cells were pre-treated for 2 h with vehicle (DMSO) or 100 nM UK5099 before OCR measurements. OCR were measured in respirometry media supplemented with 5 mM glucose and 3 mM glutamine in the presence of vehicle or UK5099. Norepinephrine (NE; 1 µM,) oligomycin A (Oligo; 4 µM), etomoxir (Eto; 40 µM) and antimycin A (AA; 4 µM) were injected where indicated. (C) Representative OCR traces averaging 4 technical replicates. (D) Quantification of non-stimulated OCR as measured in (C) from n=6 individual experiments. (E) Quantification of Eto-sensitive OCR as measured in (C) from n=6 individual experiments. Data were normalized to vehicle for each experiment.",
    "ncbi_link": "OGC1: 67863"
  },
  {
    "caption": "(F-H) Effect of Aralar1 downregulation on UK5099-induced energy expenditure. Primary brown adipocytes were transfected with Scramble RNA (Scramble) or siRNA for Aralar1 (Aralar1 KD). Cells were pre-treated for 2 h with vehicle (DMSO) or 100 nM UK5099 before OCR measurements. OCR were measured in respirometry media supplemented with 5 mM glucose and 3 mM glutamine in the presence of vehicle or UK5099. Norepinephrine (NE; 1 µM), oligomycin a (Oligo; 4 µM), etomoxir (Eto; 40 µM) and antimycin a (AA; 4 µM) were injected where indicated. (F) Representative OCR traces averaging 4 technical replicates. (G) Quantification of non-stimulated OCR as measured (G) from n=4 individual experiments. Data were normalized to vehicle for each experiment. (H) Quantification of Eto-sensitive OCR as measured in (F) from n=4 individual experiments.",
    "ncbi_link": "Aralar1: 78830"
  },
  {
    "caption": "(I) Brown adipocytes transfected with Scramble RNA or Aralar1 siRNA were treated for 24 hours with vehicle (DMSO) or 10 µM UK5099. Data shows quantification of the ratio of aspartate to glutamate abundance as measured by GC-MS from n=3 individual experiments.",
    "ncbi_link": "Aralar1: 78830"
  },
  {
    "caption": "B Plasmids encoding truncated mutants of the Smad6 MH2 domain were co-transfected into HEK293 cells with HA-tagged Pellino-1N plasmid. Cell lysates were immunoprecipitated with anti-HA antibody and immunoblotted with anti-Myc antibody. Data are representative of at least three independent experiments. IP, immunoprecipitation; IB, immunoblot; TCL, total cell lysates.",
    "ncbi_link": "Smad6: 4091"
  },
  {
    "caption": "C, D The SBE-Luc reporter plasmid was co-transfected with an empty vector, Myc-Smad6 (400-441), or full-length Smad6-expressing plasmids into CMT-93 cells, respectively. After 24 h, cells were treated with TGF-β1 for 2 h and luciferase activities were measured and normalized. Data were statistically analyzed by a t-test and show the mean ± SD of three independent experiments. **P < 0.05, ***P < 0.001.",
    "ncbi_link": "luciferase: 
Smad6: 17130
Smad6: 4091"
  },
  {
    "caption": "C, D The 5xNF-κB-Luc reporter plasmid was co-transfected with an empty vector, Myc-Smad6 (400-441), or full-length Smad6-expressing plasmids into CMT-93 cells, respectively. After 24 h, cells were treated with LPS for 2 h and luciferase activities were measured and normalized. Data were statistically analyzed by a t-test and show the mean ± SD of three independent experiments. **P < 0.05, ***P < 0.001.",
    "ncbi_link": "luciferase: 
Smad6: 17130
Smad6: 4091"
  },
  {
    "caption": "E CMT-93 cell lines stably expressing Smad6 amino acids 400-441 were treated with LPS for the indicated time and expression of IκBα, IKKα, and phospho-IKKα/β was monitored by immunoblotting. As a positive control, CMT-93 cells were pre-treated with TGF-β1 for 2 h. CMT-93 cells stably expressing the empty vector pMSCV-puro were used as a negative control. β-actin was used as a loading control. All data are representative of three independent experiments.",
    "ncbi_link": "Smad6: 4091"
  },
  {
    "caption": "B A plasmid encoding the truncated mutant composed of Smad6 amino acids 422-441 (Myc-Smad6(422-441)) or wild-type Smad6 MH2 domain (Myc-Smad6-MH2) was co-transfected with the HA-tagged full-length Pellino-1 plasmid into HEK293 cells. Cell lysates were immunoprecipitated (IP) with anti-Myc or anti-HA antibody, and immunoblotted (IB) with anti-HA or anti-Myc antibody, respectively. The vector, CS3MTBXA-6xMyc, was transfected as a negative control. IP, immunoprecipitation; IB, immunoblot; TCL, total cell lysates. Data are representative of at least three independent experiments.",
    "ncbi_link": "Smad6: 4091"
  },
  {
    "caption": "C The Myc-Smad6(422-441) plasmid was co-transfected with full-length Flag-IRAK1, Flag-TRAF6, Flag-MyD88, or HA-Pellino-1 plasmid into HEK293 cells. Cell lysates were immunoprecipitated with the indicated antibodies and immunoblotted with anti-Myc antibody. IgG was added as a negative control for IP. Data are representative of at least three independent experiments.",
    "ncbi_link": "IRAK1: 3654
MyD88: 4615
Pellino-1: 57162
TRAF6: 7189"
  },
  {
    "caption": "D, E The SBE-Luc or 5xNF-κB-Luc reporter plasmids were co-transfected with an empty vector or the Myc-Smad6(422-441) plasmid into CMT-93 cells, respectively. After 24 h, cells were treated with TGF-β1 for 6 h or LPS for 2 h, and luciferase activities were measured and normalized.",
    "ncbi_link": "luciferase: 
Smad6: 4091"
  },
  {
    "caption": "F The BRE-Luc reporter plasmid was co-transfected with an empty vector or the Myc-Smad6(422-441) plasmid or full-length Smad6 into RAW264.7 cells, respectively. After 24 h, cells were treated with BMP4 for 6 h and luciferase activity was measured and normalized.",
    "ncbi_link": "luciferase: 
Smad6: 4091
Smad6: 17130"
  },
  {
    "caption": "G A plasmid encoding the truncated mutant composed of Smad6 amino acids 422-441 (Myc-Smad6(422-441)) or wild-type Smad6 MH2 domain (Myc-Smad6-MH2) or full-length Smad6 (Myc-Smad6) was co-transfected with HA-tagged full-length Smad4 or HA-tagged full-length Pellino-1 plasmid into HEK293 cells, respectively. Cell lysates were immunoprecipitated (IP) with anti-Myc and immunoblotted (IB) with anti-HA or anti-Myc antibody, respectively. The vector, pCS3MTBXA-6xMyc, was co-transfected with HA-Smad4 or HA-Pellino-1 as a negative control. Data are representative of at least three independent experiments.",
    "ncbi_link": "Smad6: 4091"
  },
  {
    "caption": "A Pre-treatment of Smaducin-6 reduces LPS-induced interleukin-6 (Il6) gene expression in a dose-dependent manner in RAW264.7 cells. Il6 gene expression was analyzed by qRT-PCR.",
    "ncbi_link": "Il6: 16193
interleukin-6: 16193"
  },
  {
    "caption": "B, C Pre-treatment of 100 nM Smaducin-6 or scrambled peptide (Pal-Scram #1) for 30 min inhibits (B) NF-κB-mediated luciferase gene expression when RAW264.7 cells are treated with LPS for 2 h. Luciferase activity in (B) was normalized to β-galactosidase activity.",
    "ncbi_link": "luciferase: 
β-galactosidase: "
  },
  {
    "caption": "D Peli1 knockdown or wild-type humanTHP1 cells were pre-treated with 100 nM Pal-Scram peptide and Smaducin-6 for 30 min and subsequently treated with LPS for 2 h. Il6 and Peli1 gene expression were analyzed by qRT-PCR. Data show the mean ± SD of three independent experiments.",
    "ncbi_link": "Il6: 3569
Peli1: 57162"
  },
  {
    "caption": "(A) Relative mRNA expression of Foxc1 and Foxc2 in isolated blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) from Foxc1fl/fl;Foxc2fl/fl mouse distal jejuna in sham and I/R-4h groups. Isolated epithelial cells (Epis) were used as a relative control, Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 5~9, *P<0.05, **P<0.01, n.s. = not significant. The box-and-whisker plots in (A) display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc1: 17300
Foxc2: 14234"
  },
  {
    "caption": "(B-C) Representative confocal images of the whole-mount intestine stained with CD31/LYVE1 (B), FOXC1/CD31/LYVE1 (C, left) and FOXC1/LYVE1 (C, right) in Foxc1fl/fl;Foxc2fl/fl mice. Images of maximum intensity projections (B) show the intestinal blood (green) and lymphatic (white) vasculatures from villous to submucosa. The regions in pink box 1~8 in Figure 1B are chosen for the specific images in Figure 1C. Scale bars = 50 μm. (C) Images of optical sections with high magnification chosen from specific regions shown in Figure 1B (B1~B8), with an additional channel of FOXC1 staining (red), show the up-regulation of FOXC1 in BECs (white arrows in blood vessels) and LECs (violet arrows in lymphatic vessels) at the level of villus and submucosa 4 h after I/R. Scale bars = 20 μm.",
    "ncbi_link": "Foxc1: 17300
Foxc2: 14234"
  },
  {
    "caption": "(F) Relative mRNA expression  of Foxc1  and Foxc2  in isolated CD45-CD31+ ECs  from distal jejuna 12d after Tm  treatment. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~5, *P<0.05. Data information: The box-and-whisker plots in (F) display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc1: 17300
Foxc2: 14234"
  },
  {
    "caption": "(C-E) Quantification of Chiu Score for Control and EC-Foxc-DKO (C), Control and EC-Foxc1-KO (D), and Control and EC-Foxc2-KO groups (E) at I/R-24h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 3 in C sham groups, N = 7~12 in C, D, E I/R-24h groups, *P<0.05, ****P<0.0001. The box-and-whisker plots in display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc1: 17300
Foxc2: 14234
Foxc: 14234///17300"
  },
  {
    "caption": "(I) Representative images of intestinal crypts immunostained with β-catenin and the intestinal epithelial stem cell (ISC) marker OLFM4. At I/R-48h, the nuclear translocation of β-catenin in ISCs (dotted circles) was found in the control, whereas it was seldom found in EC-Foxc-DKO mice. Paraffin sections (4 µm), (J, K) (J) Quantification of relative fluorescent intensity (FI) of β-catenin immunostaining within ISC and (K) quantification of number of OLFM4+ ISCs per crypt were performed based on Figure 2I. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~5, *P<0.05, n.s. = not significant. The box-and-whisker plots in display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "(L) Representative images of intestinal mucosa labeled with Cyclin D1 (CCND1) in EC-Foxc-DKO mice compared with Control group in sham, 24h and 48h after I/R. Paraffin sections (4 µm), (M) Quantification of the number of CCND1+ epithelial cells per crypt based on Figure 2L. Data are box-and-whisker plots, Kruskal-Wallis One-way ANOVA test, each symbol represents one mouse, N = 4~6, **P<0.01, ****P<0.0001, n.s.=not significant. The box-and-whisker plots in display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "Chiu Score analysis from H&E stained distal jejunum 24h after I/R for Control (Foxc1f/f;Foxc2f/f) and LEC-Foxc-DKO (Vegfr3-CreERT2;Foxc1f/f;Foxc2f/f) mice (B), Control (Foxc1f/f) and LEC-Foxc1-KO (Vegfr3-CreERT2;Foxc1f/f) mice (C) Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N=9~13, *P<0.05, **P<0.01. display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Cre: 2777477
Vegfr3: 14257
Foxc1: 17300
Foxc2: 14234
Foxc: 14234///17300
ERT2: 26417"
  },
  {
    "caption": "(F) Representative images of crypts immunostained with OLFM4 and β-catenin in control and LEC-Foxc-DKO mice 24h after I/R. The accumulation of β-catenin in the nuclei of ISCs (dotted circles) was found in Control mice but inhibited in LEC-Foxc-DKO mice. Paraffin sections (4 µm), scale bars = 20 μm.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "(A) Representative images of intestinal whole-mount VEGFR2/CD31 (green/red) immunostaining show increased VEGFR2 (green) expression at the angiogenic front of villous blood capillaries in control mice at I/R-18.5h. In EC-Foxc-DKO mice, the increase of VEGFR2 is inhibited in villous blood vessels and the blood vasculatures are damaged (arrow). (B) Representative images of intestinal whole-mount VEGFR3/LYVE1 (red/green) immunostaining. 18.5h after I/R, VEGFR3 (red) is increased in lacteals especially at the lacteal tips in the control but is inhibited in the EC-Foxc-DKO lacteals (arrow).",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "(D) Violin plots of the Rspo3 expression in trophocytes and LECs in intestine at I/R-18.5h. Mann-Whitney U test, each symbol represents one cell; N = 12 and 12 in control and EC-Foxc-DKO trophocytes, respectively; N=16 and 5 in control and EC-Foxc-DKO LECs.",
    "ncbi_link": "Foxc: 14234///17300
Rspo3: 72780"
  },
  {
    "caption": "(E) Validation study by qPCR for the detection of relative mRNA expression of Rspo3 in the sorted intestinal LECs at I/R-18.5h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 5~6, **P<0.01. The box-and-whisker plots display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Rspo3: 72780"
  },
  {
    "caption": "(D) Violin plots of the Cxcl12 expression in fibroblasts and telocytes/trophocytes. Mann-Whitney U test, each symbol represents one cell, N = 67 and 98 in control and EC-Foxc-DKO mice, respectively; n.s. = not significant.",
    "ncbi_link": "Cxcl12: 20315
Foxc: 14234///17300"
  },
  {
    "caption": "(F) Relative mRNA expression of Cxcl12 in Dynabeads-isolated ECs (CD45-CD31+) from distal jejunum. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 6~10, *P<0.05. The box-and-whisker plots display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Cxcl12: 20315"
  },
  {
    "caption": "FOXC1 and FOXC2 co-occupy as well as the ECRs and promoters of CXCL12 in HUVECs (D). Quantitative-ChIP assay was performed using rabbit (R) anti-FOXC1 and mouse (M) anti-FOXC2 antibodies to analyze the recruitment of FOXC on promoters and/or ECRs in HUVECs respectively. Values were quantified against IgG controls. Data are mean ± SEM, paired t-test, each symbol represents data collected from one experiment, N = 4, * P<0.05, ** P<0.01, n.s.=not significant.",
    "ncbi_link": "CXCL12: 6387"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (C) Representative images of crypts immunostained with OLFM4 and β-catenin in PBS/RSPO3 treated EC-Foxc-DKO mice 24h after I/R. The accumulation of β-catenin in the nuclei of ISCs (dotted circles) was found in RSPO3 rescued mice. Paraffin sections (4 µm), (D) Quantification of relative fluorescent intensity (FI) of β-catenin immunostaining within ISC and (E) quantification of the number of OLFM4+ ISCs were performed based on Figure 9C. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, *P<0.05.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (F) Representative images of immunostaining of CCND1 in intestines in PBS/RSPO3 treated EC-Foxc-DKO mice at I/R-24h. Scale bars = 100 µm. (G) Quantification of the number of CCND1+ epithelial cells per crypt at I/R-24h are based on Figure 9F. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 7, **P<0.01.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (H) Relative mRNA expression of Rspo3 in sorted LECs and Cxcl12 in sorted BECs from intestines of PBS/RSPO3 treated EC-Foxc-DKO mice at I/R-18.5h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, *P<0.05.",
    "ncbi_link": "Cxcl12: 20315
Foxc: 14234///17300
Rspo3: 72780"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. Representative images of H&E staining show the rescue effects of RSPO3 in intestinal mucosa LEC-Foxc-DKO (I) mice as well as their control mice 24h after I/R. Red numbers indicate the Chiu scores. Quantification of Chiu Score for the intestines at I/R-24h are based H&E staining as shown in Figure 9A and 9I. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 6~13, **P<0.01.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "In RSPO3 rescue experiment, each mouse was treated with 5 μg RSPO3 in 100μL PBS by retro-orbital injection 30 min before ischemia. PBS treated mice were used as vehicle control. (K) Representative images of CD31/LYVE1 immunostaining in the intestines of PBS/RSPO3 treated LEC-Foxc-DKO mice at I/R-24h. (L, M) Quantification of the vessel density (L) (= vessel area/total intestinal tissue area x 100%) for the blood (B) and/or lymphatic (L) vessels (markers listed below the graph were used to identify B and L) as well as the measurement of lacteal length (M) was performed based on Figure 9K. The Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 7, **P<0.01, n.s.=not significant.",
    "ncbi_link": "Foxc: 14234///17300"
  },
  {
    "caption": "In CXCL12 rescue experiments, mice were treated with 50μg/kg CXCL12 in PBS by retro-orbital injection 30 min before ischemia. Mice treated with PBS were used as control. (H) Representative confocal images of CD31 immunostaining of distal jejuna in PBS- and CXCL12- treated EC-Foxc-DKO mice after I/R at 24h. Paraffin sections (15 µm), scale bars = 100 μm. L represents the lacteal length measured in Figure 10J. (I, J) (I) Quantification of CD31+ vessel density (% = total CD31+ vessel area/total intestinal tissue area x 100%) and (J) quantification of lacteal length were performed based on Figure 10H. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 4~6, **P<0.01.",
    "ncbi_link": "Foxc: 17300///14234"
  },
  {
    "caption": "In CXCL12 rescue experiments, mice were treated with 50μg/kg CXCL12 in PBS by retro-orbital injection 30 min before ischemia. Mice treated with PBS were used as control. (K) Relative mRNA expression of Rspo3 in sorted intestinal LECs from PBS/CXCL12 treated EC-Foxc-DKO mice at I/R-18.5h. Data are box-and-whisker plots, Mann-Whitney U test, each symbol represents one mouse, N = 5~6, n.s.=not significant. The box-and-whisker plots in display the median value (central band in the box), second and third quartiles (bottom and top ends of the box, respectively) as well as minimum/maximum values (whiskers blow/above the box) of the data sets.",
    "ncbi_link": "Foxc: 17300///14234
Rspo3: 72780"
  },
  {
    "caption": "Western blot analysis of total brain lysates of wild type, Tmem106b-/-, Grn-/- and Grn-/-/Tmem106b-/- mice using antibody 6F2 to detect TMEM106B. (4.5-month-old mice with the given genotype; n = 3 biological replicates per genotype).",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Hind limb clasping test wild type, Tmem106b-/-, Grn-/-, Grn+/-/Tmem106b-/- and Grn-/-/Tmem106b-/- mice. Representative pictures are shown of 3 mice analyzed for each genotype at 3 months of age.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Rotarod performance of wild type, Tmem106b-/-, Grn-/-, Grn+/- /Tmem106b-/- and double knockout animals at 3 to 4 months of age. Number of animals used for analysis, 10 wild type, 12 Tmem106b-/-, 5 Grn-/-, 7 Grn+/-/Tmem106b-/-, 3 Grn-/-/Tmem106b-/- mice.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Representative picture of a 4.5-month-old double knockout (Grn-/-/Tmem106b-/- ) mouse after manual flip.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (A) Comparison of differentially expressed brain mRNAs from Tmem106b-/- and wild type mice. From 680 detected genes 21 are significantly upregulated, while 10 are significantly reduced.",
    "ncbi_link": "Tmem106b: 71900"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (B) Comparison of Grn-/- and wild type mice. From 680 detected genes 12 are significantly upregulated, while 6 are significantly reduced.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "Volcano plot of differentially expressed brain mRNAs of 4.5-month-old mice (n = 3 biological replicates per genotype) detected by the Neuropathology panel of NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for all volcano plots. Gliosis and Myelination related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (C) Volcano plot for Grn-/-/Tmem106b-/- and wild type mice. From 680 detected genes 79 are significantly upregulated, while 24 are significantly reduced.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "D. Display of differently expressed genes overlapping between the analyzed genotypes from (A-C). Overlap was considered if a gene was significantly changed in the respective mouse models with more than 20% change in at least one mouse model. Note that 9 genes are significantly altered in all 3 genotypes in comparison to the wild type. 7 genes are exclusively overlapping between the Grn-/- and the Grn-/-/Tmem106b-/- mice. Tmem106b-/- and Grn-/-/Tmem106b-/- mice share 15 significantly altered genes. Tmem106b-/- and Grn-/- mice share one significant altered gene. Data represent the mean ± SD.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type 4 Tmem106b-/- mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (A) Comparison of differentially expressed mRNA of Tmem106b-/- mice in comparison to wild type mice. From 622 detected genes 21 are significantly upregulated, while 12 are significantly reduced.",
    "ncbi_link": "Tmem106b: 71900"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type, 4 Grn-/ mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (B) Comparison of differentially expressed mRNA in Grn-/- and wild type mice. From 622 detected genes 32 are significantly upregulated, while only 1 is significantly reduced.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "Analysis of brain mRNA expression of 4.5-month-old mice (5 wild type 5 Grn-/-/Tmem106b-/- mice) detected by the Neuroinflammation panel by NanoString. Expression changes were only taken into consideration when the extent of change was above 20% as indicated by vertical lines for in all volcano plots. Gliosis related genes are highlighted if changes are above 20%. Fold changes are displayed after log2 transformation. (C) Volcano plot of differentially expressed brain mRNAs from Grn-/-/Tmem106b-/- mice in comparison to wild type mice. From 622 detected genes 110 are significantly upregulated, while 16 are significantly reduced.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "D. Display of differently expressed genes overlapping between the analyzed genotypes from (A-C). Overlap was considered if a gene was significantly changed in the respective mouse models with more than 20% change in at least one mouse model. Note that 19 genes are significantly altered in all 3 genotypes in comparison to the wild type. 17 genes are exclusively overlapping between the Grn-/- and the Grn-/-/Tmem106b-/- mice. Tmem106b-/- and Grn-/-/Tmem106b-/- mice share 17 significantly altered genes. Data represent the mean ± SD.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "In vivo 18F-GE180 TSPO μPET imaging. Two female Grn-/-/Tmem106b-/- and five female wild type mice underwent longitudinal TSPO μPET at 2.0 and 3.5 months of age. All analyses were performed by PMOD (V3.5, PMOD technologies). Normalization of injected activity was performed by the previously validated myocardium correction method.",
    "ncbi_link": "Grn: 14824
Tmem106b: 71900"
  },
  {
    "caption": "Representative confocal images of control (CTL-1) and OPA1S545R patient fibroblasts treated with OPA1, DNM1L, or non-targeting (NT) siRNAs for 72 hours and imaged as described in A. Scale bar=20μm. Passage number between P12-14. Mitochondrial morphology quantification of D. Data represent mean ± SD of three independent experiments, (3219-5857 cells per cell line), One-way ANOVA; ****p < 0.0001, ns; not significant.",
    "ncbi_link": "DNM1L: 10059
OPA1: 4976"
  },
  {
    "caption": "Representative confocal images of control (CTL-1) and OPA1S545R patient fibroblasts treated with 50μM cycloheximide (CHX) where indicated for 6 hours. Imaging as described in A. Scale bar=20μm. Passage number between P14-P15. Mitochondrial morphology quantification of F. Data represent mean ± SD of two independent experiments, (879-4154 cells per cell line), One-way ANOVA; ****p < 0.0001, ns; not significant.",
    "ncbi_link": "OPA1: 4976"
  },
  {
    "caption": "Representative confocal images of control (CTL-1) and OPA1S545R patient fibroblasts treated with OPA1, DNM1L, PGS1, and non-targeting (NT) siRNAs or indicated combinations for 72 hours. Mitochondria (anti-TOM40, green) and nuclei (DAPI, blue). Scale bar=20μm. Passages number between P10-15. Mitochondrial morphology quantification of (A) using control fibroblasts with fragmented (OPA1 siRNA), normal (non-targeting NT siRNA), and hypertubulated (DNM1L siRNA) mitochondria. Data represent mean ± SD of three independent experiments, One-way ANOVA (905-3695 cells per cell line), (% fragmented); ; ****p < 0.0001, ns; not significant..",
    "ncbi_link": "TOM40: 
DNM1L: 10059
OPA1: 4976
PGS1: 9489"
  },
  {
    "caption": "Representative confocal images of wild type (WT) and Opa1Crispr MEFs treated with NT or Pgs1 siRNA for 72 hours. Live imaging of mitochondria (mitoYFP, green) and nuclei (NucBlue, blue). Scale bar=10μm. Mitochondrial morphology quantification of (C) using WT MEFs treated with Opa1 siRNA (fragmented), NT siRNA (normal), or Dnm1l siRNA (hypertubulated) ground truth training sets. Data represent mean ± SD of three independent experiments, One-way ANOVA (6613-8758 cells per cell line), (% fragmented) ; ****p < 0.0001, ns; not significant.",
    "ncbi_link": "Dnm1l: 74006
Opa1: 74143
Pgs1: 74451"
  },
  {
    "caption": "Representative confocal images of WT, Opa1Crispr MEFs complemented with pLenti-Opa1, Opa1CrisprPgs1Crispr MEFs and Pgs1Crispr MEFs complemented with pLenti-Pgs1 by lentiviral delivery. Live imaging of mitochondria (mitoYFP, green) and nuclei (NucBlue, blue). Scale bar=10μm. Supervised ML mitochondrial morphology quantification of (E) using WT MEFs treated with Opa1 siRNA (fragmented), NT siRNA (normal), or Dnm1l siRNA (hypertubulated) training sets. Data represent mean ± SD of three independent experiments, One-way ANOVA (691-3990 cells per cell line), (% fragmented) ; ****p < 0.0001, ns; not significant..",
    "ncbi_link": "Crispr: 
Dnm1l: 74006
Opa1: 74143
Pgs1: 74451"
  },
  {
    "caption": "Representative confocal micrographs of MEFs WT and Opa1Crispr MEFs treated with indicated siRNAs for 72 hours. Mitochondria (anti-TOM40, green) and nuclei (DAPI, blue). Scale bar=10μm. Supervised ML mitochondrial morphology quantification of (B) using WT MEFs with fragmented (Opa1 siRNA), normal (non-targetting NT siRNA), and hypertubular (Dnm1l siRNA) mitochondria. Data represent mean ± SD of three independent experiments, One-way ANOVA (726-4236 cells per cell line), (% fragmented); *** p < 0.001, ****p < 0.0001, ns; not significant.",
    "ncbi_link": "Crispr: 
Dnm1l: 74006
Opa1: 74143"
  },
  {
    "caption": "Representative confocal micrographs of MEFs WT, Pgs1Crispr and Dnm1lCrispr MEFs treated with indicated siRNAs for 72 hours. Mitochondria (anti-TOM40, green) and nuclei (DAPI, blue). Scale bar=10μm. Supervised ML mitochondrial morphology quantification of (G) using WT MEFs with fragmented (Opa1 siRNA), normal (non-targetting NT siRNA), and hypertubulated (Dnm1l siRNA) mitochondria. Data represent mean ± SD of >3 independent experiments, (3096-7238 cells per cell line), One-way ANOVA (% fragmented) ; *p < 0.05, ** p < 0.01, ****p < 0.0001, ns; not significant.",
    "ncbi_link": "Crispr: 
Dnm1l: 74006
Opa1: 74143
Pgs1: 74451"
  },
  {
    "caption": "Representative transmission electron micrographs of MEFs of the indicated genotypes showing loss of lamellar cristae in Opa1Crispr and Opa1CrisprPgs1Crispr MEFs. Scale bar=200nm. Quantification of (C) of mitochondrial ultrastructure; outer membrane/inner membrane ration (IMM/OMM) and cristae number per mitochondrion. Violin plot of >50 mitochondria per cell line, One-way ANOVA; *p < 0.05, ** p < 0.01, ****p < 0.0001, ns; not significant.",
    "ncbi_link": "Crispr: 
Opa1: 74143
Pgs1: 74451"
  },
  {
    "caption": "mtDNA content in MEFs from (F) was quantified by amplification of MTTL1, 16S and MT-ND1 genes relative to the GAPDH nuclear gene in MEFs. Data represent mean ± SD of three independent experiments, One-way ANOVA; ****p < 0.0001, ns; not significant. mtDNA content in WT and mutant MEFs treated with indicated siRNAs for 72 hours was quantified by amplification of MTTL1, 16S and ND1 genes relative to the GAPDH nuclear gene in MEFs. Data represent mean ± SD of three independent experiments, One-way ANOVA; **p < 0.01, ****p < 0.0001, ns; not significant.",
    "ncbi_link": "GAPDH: 
16S: 27471
ND1: 17716
MTTL1: 17735"
  },
  {
    "caption": "B. Distribution of PWWP2B mutations identified in 25 STAD patients. Distribution of PWWP2B mutations identified in the TCGA PanCancer Atlas stomach adenocarcinoma dataset (Network, 2014). Distribution of PWWP2B mutations identified in a large-scale colorectal adenocarcinoma genomic study.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "E. Overall survival curve of 25 gastric cancer patients with and without PWWP2B mutations.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "B. The interaction between exogenous PWWP2B and UHRF1. The indicated plasmids were transfected into 293T cells. After 24 hours, the transfected cell lysates were immunoprecipitated (IP) using an anti-Myc antibody and subjected to Western blotting analysis using the indicated antibodies. The bottom panel shows equal volumes of cell lysates immunoblotted with the indicated antibodies.",
    "ncbi_link": "PWWP2B: 170394
UHRF1: 29128"
  },
  {
    "caption": "E. Myc-UHRF1 and either GFP-PWWP2B WT or its serial deletion mutants were co-transfected into 293T cells. The cell lysates were immunoprecipitated with the anti-Myc antibody and then immunoblotted with the indicated antibodies.",
    "ncbi_link": "GFP: 
Myc: 
PWWP2B: 170394
UHRF1: 29128"
  },
  {
    "caption": "Cell lysates of 293T expressing Myc-UHRF1 WT or Myc-UHRF1-D4 mutants were incubated with 2 ug of purified GST or GST-PWWP2B-N for 1 h at 4 °C. After pull-down with GST-beads, the bound complex was analyzed by Western blots.",
    "ncbi_link": "Myc: 
UHRF1: 29128"
  },
  {
    "caption": "F. HeLa cells were transfected with GFP-PWWP2B WT or deletion mutant expression plasmids, and 24 h later, the cells were treated with laser microirradiation (top panel). The cells with positive GFP expression on the laser stripes are presented in the bar graph (bottom panel). The results represent the average of three independent experiments. The error bars indicate the standard deviation.",
    "ncbi_link": "GFP: 
PWWP2B: 170394"
  },
  {
    "caption": "H. GFP-PWWP2B-A2A3 deletion mutant translocates to the DNA damage sites. HeLa cells were transfected with GFP-tagged deletion mutant expression plasmids, and 24 h later, the cells were treated with laser microirradiation (left panel). The cells with positive GFP expression on the laser stripes after 10 minutes were counted and presented in the bar graph (right panel). The results represent the average of three independent experiments. The error bars indicate the standard deviation for the cells transfected with each expression plasmid.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "I-J. HeLa cells depleted with either control or UHRF1 siRNAs were transfected with the GFP-PWWP2B-A2A3 (I) and GFP-PWWP2B WT (J) expression plasmid. After 24 h, the cells were subjected to laser microirradiation. The laser stripes were examined at the indicated time points. The intensity of each laser stripes in each time point was measured by averaging values from indicated number of cells and graphed in the right panel.",
    "ncbi_link": "GFP: 
PWWP2B: 170394
UHRF1: 29128"
  },
  {
    "caption": "The intensity of each laser stripes in each time point was measured by averaging values from indicated number of cells and graphed in the right panel. K. HeLa cells depleted with either control or PWWP2B siRNA were transfected with GFP-UHRF1 expression plasmids. After 24 h, the cells were subjected to laser microirradiation. The laser stripes were examined at the indicated time points.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "D-G. Quantification of radiation-induced RAD51, BRCA1, and 53BP1 foci formation in HeLa cells treated with the indicated siRNAs. All data were obtained from over cells (open circles), and the mean values are shown as red bars (upper panel). Immunofluorescence analysis of irradiation-induced RAD51, BRCA1, and 53BP1 foci formation. HeLa cells transfected with either control or PWWP2B siRNAs were synchronized in S phase by a double thymidine block and exposed to 0 or 2 Gy of IR. The cells were incubated for 2 h, fixed, and subjected to staining with RAD51 (D and E), BRCA1 (F), or 53BP1 (G) antibodies. The cells in S phase were identified by Cyclin A staining. (E) The siPWWP2B-resistant PWWP2B WT expression vector was transfected into HeLa cells after siRNA-mediated PWWP2B depletion. IR-induced RAD51 foci formation was examined by immunofluorescence.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "A. Immunoblot analysis of RAD51, BRCA1, or 53BP1 protein levels in PWWP2B-depleted HeLa cells.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "C-D. Quantification of radiation-induced RPA2 or S4/S8 phosphorylated RPA foci formation in PWWP2B-depleted HeLa cells. All data were obtained from over 100 cells (open circles), and the mean values are shown as red bars (upper panel).Immunofluorescence analysis of irradiation-induced RPA2 or S4/S8 phosphorylated RPA2 foci formation. HeLa cells treated with either control or PWWP2B siRNAs were exposed to 0 or 2 Gy of IR. The cells were incubated for 2 h, fixed, and subjected to staining with RPA2 (C), or S4/S8 phosphorylation-specific RPA2 (D) antibodies (bottom panel).",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "A. Immunofluorescence analysis for irradiation-induced MRE11 foci formation (left panel). HeLa cells transfected with either control siRNA, siPWWP2B or siUHRF1 were irradiated, fixed and subjected to staining with MRE11 and γH2AX antibodies. More than 100 nuclei per condition were counted.The percentage of MRE11-positive cells is presented as a bar graph (right panel). The results represent the average of three independent experiments. The error bars indicate standard deviation.",
    "ncbi_link": "PWWP2B: 170394
UHRF1: 29128"
  },
  {
    "caption": "B. HeLa cells expressing GFP-MRE11 were treated with control siRNA or siRNAs against PWWP2B. After 48 h, the cells were subjected to laser microirradiation. Stripes on the laser were examined at the indicated time points (upper panel).The intensity of the laser stripes at the time points was determined. The average intensity values from 10 cells were graphed in the bottom panel.",
    "ncbi_link": "PWWP2B: 170394"
  },
  {
    "caption": "C. The interaction between PWWP2B and MRE11. HA-PWWP2B and Myc-MRE11-expressing vectors were transfected into 293T cells. After 24 h, the cell lysates were immunoprecipitated with anti-HA antibody, followed by immunoblot analysis with the indicated antibodies.",
    "ncbi_link": "HA: 
PWWP2B: 170394"
  },
  {
    "caption": "B-C. Comparison of IR-induced foci formation for either RAD51 or BRCA1 in HeLa cells transfected with the indicated siRNAs. Quantification of radiation-induced RAD51 or BRCA1 foci formation in PWWP2B alone, UHRF1 alone or PWWP2B and UHRF1-depleted HeLa cells. All data were obtained from over 100 cells (open circles), and the mean values are shown as red bars (upper panel).Immunofluorescence analysis of irradiation-induced RAD51 or BRCA1 foci formation. HeLa cells treated with the indicated siRNAs were exposed to 0 or 2 Gy of IR. The cells were incubated for 2 h, fixed, and subjected to staining with RAD51 (B), or BRCA1 (C) antibodies (bottom panel).",
    "ncbi_link": "PWWP2B: 170394
UHRF1: 29128"
  },
  {
    "caption": "(A) Northern blot experiments show the expression of RsaI during growth phase in the HG001 strain in MHB medium with or without the addition of 1,5 g/L of D-glucose. Glucose was added either at the beginning of growth (+ glucose, left panel) or after 3h of growth (right panel).",
    "ncbi_link": "RsaI: "
  },
  {
    "caption": "(B) Northern blot experiment shows the expression of RsaI during growth phase in the HG001, ∆ccpA mutant strain, and ∆codY mutant strain, in MHB medium with (+) or without (-) the addition of 1,5 g/L of D-glucose.",
    "ncbi_link": "RsaI: 
codY: 3920255
ccpA: 3920528"
  },
  {
    "caption": "(C) Northern blot experiment shows the expression of RsaI in the HG001 and ∆ccpA mutant strains. Total RNA was prepared after 2, 3, 4, 5 and 6h of culture in BHI medium at 37°C.",
    "ncbi_link": "RsaI: 
ccpA: 3920528"
  },
  {
    "caption": "(D) Northern blot analysis of RsaI in the HG001 strain grown in MHB medium with or without the addition of 1 g/L of glucose, fructose or xylose. For all the experiments, loading controls were done using the expression of 5S rRNA (5S) as revealed after hybridization of the membranes with a specific probe. However for these controls, we used aliquots of the same RNA preparations but the migration of the samples was performed in parallel to the experiments on a separate agarose gel because RsaI and 5S rRNA have very similar sizes.",
    "ncbi_link": "5S: 
5S rRNA: 
RsaI: "
  },
  {
    "caption": "(B) Gel retardation assays show the formation of the complex between RsaI and icaR, glcU_2 and fn3K mRNAs. The 5' end-labeled wild-type RsaI (RsaI), RsaI mutant 3 (RsaI mut3, deletion of the two G-track motifs), and RsaI mutant 4 (RsaI mut4, deletion of the C/U rich unpaired interhelical region) were incubated with increasing concentrations of mRNAs: lane 1, 0 nM; lane 2, 25 nM; lane 3, 50 nM; lane 4, 100 nM and lane 5, 200 nM. Below the gels, the predicted interactions between RsaI and its targets are shown. Translation start codons are in green and SD is for Shine Dalgarno sequence. Graphs represented the % of complex formed between either RsaI or its two mutant forms (RsaI mut3 and RsaI mut4) and the target mRNA (icaR, glcU_2, fn3K) as the function of mRNA concentrations.",
    "ncbi_link": "fn3K: 
glcU_2: 
RsaI: 
icaR: 3921483"
  },
  {
    "caption": "(C) Gel retardation assays show the formation of the complex between RsaI and RsaG. The 5' end-labeled wild-type RsaI (RsaI), RsaI mutant 2 (RsaI mut2), RsaI mutant 4 (RsaI mut4), and RsaI mutant 1 (RsaI mut1) were incubated with increasing concentrations of RsaG given in nM on the top of the autoradiographies.",
    "ncbi_link": "RsaG: 
RsaI: "
  },
  {
    "caption": "(A) Toe-print assays showing the effect of RsaI on the formation of the ribosomal initiation complex of glcU_2 and fn3K mRNAs, respectively. Lane 1 : incubation control of mRNA alone; lane 2 : incubation control of mRNA with 30S subunits; lane 3: incubation control of mRNA with RsaI; lane 4 : formation of the ribosomal initiation complex containing mRNA, 30S and the initiator tRNAfMet (tRNAi); lanes 5 to 9 : formation of the initiation complex in the presence of increasing concentrations of RsaI, respectively : 50 nM (lane 5), 100 nM (lane 6), 150 nM (lane 7), 300 nM (lane 8), and 400 nM (lane 9). Lanes T, A, C, G: sequencing ladders. The Shine and Dalgarno (SD) sequence, the start site of translation (START) and the toe-printing signals (+16) are indicated. At the bottom of the gels are shown the predicted interactions between RsaI and its targets. Translation start codons are in green, and the Shine and Dalgarno (SD) sequence is underlined, the arrowheads depict the toe-printing signals.",
    "ncbi_link": "fn3K: 
glcU_2: 
RsaI: "
  },
  {
    "caption": "(B) The β-galactosidase activity (Miller Units) has been measured from various fusions expressed from a plasmid which also carries rsaI gene under its own promoter: PrpoB::glcU::lacZ::rsaI, PrpoB::fn3K::lacZ::rsaI, PrpoB::treB::lacZ::rsaI, PrpoB::HG001_1242::lacZ::rsaI, and PrpoB::HG001_2520::lacZ::rsaI expressed in the mutant strain HG001-∆rsaI. The same constructs were made in the absence of rsaI gene. For the fn3K-lacZ fusion, we also used an additional construct PrpoB::fn3K::lacZ::rsaImut4 expressing both the fusion FN3K-LacZ protein and RsaI mut4. The β-galactosidase activity was normalized for bacterial density and the results represented the mean of four independent experiments. The error bars are standard deviations and the statistical significance was determined using the Student's t-test. * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001, ns is for not significant.",
    "ncbi_link": "fn3K: 
glcU: 
lacZ: 
rsaI: 
treB: 
FN3K: 
HG001_1242: 
HG001_2520: 
LacZ: 
PrpoB: 
RsaI: 
β-galactosidase: "
  },
  {
    "caption": "(B) Gel retardation assays show the formation of the complex between RsaI and icaR full length, icaR SUBST, icaR-5'UTR, and icaR-3'UTR. The 5' end-labeled of RsaI was incubated with increasing concentrations of the various mRNAs. UTR is for untranslated region, SUBST stands for the substitution of UCCCCUG sequence by AGGGGAC. This mutation, which is located in the 3'UTR of icaR, significantly destabilizes the long-range interaction, and enhances icaR translation. Lane C represents binding between radiolabelled RsaI and full-length icaR mRNA (50 nM). Due to the rather short migration of the gel, the full-length mRNA is still observed in the pocket.",
    "ncbi_link": "RsaI: 
icaR: 3921483"
  },
  {
    "caption": "(C) In vivo effect of RsaI on PIA-PNAG synthesis in the S. aureus wild-type (WT) 132 strain, the ∆rsaI mutant, and the strain carrying a deletion of icaR 3'UTR (∆3'UTR). This last mutant strain has been transformed with the pES plasmids expressing rsaI or rsaI mut5. The PIA-PNAG exopolysaccharide biosynthesis was quantified using dot-blot assays. Serial dilutions (1/5) of the samples were spotted onto nitrocellulose membranes and PIA-PNAG production was detected with specific anti-PIA-PNAG antibodies. RsaI was detected in the same samples by Northern blot using a probe directed against RsaI. Ethidium bromide staining of rRNA was used as loading controls of the same gel.",
    "ncbi_link": "rsaI: 
RsaI: 
icaR: 3921483"
  },
  {
    "caption": "(A) Ternary complex formation between RsaI, various mRNAs (glcU_2, HG001_00942 and HG001_1242), and RsaG. The 5'-end labeled RsaI was incubated with increasing concentrations of the target mRNA alone or in the presence of 50 nM of RsaG. The various complexes are notified on the sides of the autoradiographies.",
    "ncbi_link": "glcU_2: 
HG001_00942: 
HG001_1242: 
RsaG: 
RsaI: "
  },
  {
    "caption": "(B) RsaG does not form stable complexes with glcU_2 and HG001_01242. Binding assays were done in the presence of 5' end-labeled RsaG and either cold RsaI (300 nM) or increasing concentrations of glcU_2 and HG001_01242.",
    "ncbi_link": "glcU_2: 
HG001_01242: 
RsaG: 
RsaI: "
  },
  {
    "caption": "(C) Measurements of the half-lives of RsaI and RsaG in HG001-∆rsaG or HG001-∆rsaI mutant strains using Northern blot experiments. The cells were treated with rifampicin at 4h of growth and total RNAs were extracted after 2, 4, 8, 15, 30 and 60 min at 37°C in BHI. 5S rRNA was probed to quantify the yield of RNAs in each lane using the same samples, which were however run on two different gels. Calculated half-lives are shown beneath the autoradiographies and are the average of 2 experiments. The data were normalized to 5S rRNA.",
    "ncbi_link": "rsaG: 
rsaI: 
RsaG: 
RsaI: "
  },
  {
    "caption": "E Influence of mutations in CSPα (ΔL116, L115R) on the interactions with ZDHHC17 in primary hippocampal neurons. BRET and LuC ratios were systematically quantified for interactions with wild-type and mutant CSPα fusion proteins.",
    "ncbi_link": "CSPα: 80331"
  },
  {
    "caption": "E. Ectopic expression of CG14044   in the  wing pouch (GFP  area indicated by the dotted line) induces caspase  activation and DNA  fragmentation (TUNEL) in the  larval disc, melanization in the  pupal wing    (arrow head) and a structure defect in the adult wing. Data information: Scale bars, 100 μm in E (cleaved caspase) and 20 μm in E (TUNEL) and 500 μm in E (pupae and adult wing).",
    "ncbi_link": "CG14044: 33702"
  },
  {
    "caption": "H. Deletion of the BH3 motif suppresses Sayonara-induced caspase  activation, which was detected by the caspase  sensor GC3Ai. I. Quantification of GC3Ai  positive areas with Synr  WT and the BH3 motif deletion mutant. Data information: Statistical significance was determined using one-way ANOVA with Dunnett's post hoc test. Scale bars, 100 μm in",
    "ncbi_link": "Sayonara: 33702
Synr: 33702"
  },
  {
    "caption": "A-D. The Synr-induced wing  structural defect is suppressed by knockdown of Debcl, Buffy  or DCP1. Data information: Scale bars, 500 μm in A",
    "ncbi_link": "Buffy: 36251
Synr: 33702
DCP1: 37790
Debcl: 53585"
  },
  {
    "caption": "F. Synr-induced caspase  activation is suppressed by knockdown of Debcl. G. GC3Ai signals are suppressed by knockdown of Debcl  or Buffy  Data information: Scale bars, 50 μm in F and G",
    "ncbi_link": "Buffy: 36251
Synr: 33702
Debcl: 53585"
  },
  {
    "caption": "H-I. Lysates from HEK293T  cells that express Flag-Debcl  or Flag-Buffy  were incubated with GST  or GST-Synr   bound to glutathione-Sepharose. Flag-Debcl  or Flag-Buffy  is pulled down  with GST-Synr   but not with GST.",
    "ncbi_link": "Flag: 
Buffy: 36251
Debcl: 53585"
  },
  {
    "caption": "A. Ectopic expression of Synr   induces autolysosome  accumulation, which was detected by Lysotracker, in the wing disc. B. Ectopic expression of Synr   also induces autophagosome  accumulation, which was detected by mCherry-atg8a. The dotted square regions are magnified in the right pictures. Data information: Scale bars, 100 μm in A and H, 50 μm in B",
    "ncbi_link": "Synr: 33702"
  },
  {
    "caption": "D-F. Knockdown of Atg2  or Atg8a  suppresses the wing  structural defect that is induced by Synr. Data information: Scale bars, 500 μm in D.",
    "ncbi_link": "Atg2: 38344
Atg8a: 32001
Synr: 33702"
  },
  {
    "caption": "Synr-induced caspase  activation is suppressed by inhibition of autophagy  (atg2, atg8a  RNAis) in a similar manner to apoptosis  inhibition (Debcl, Dcp-1 RNAis). Data information: Scale bars, 100 μm in",
    "ncbi_link": "atg2: 38344
atg8a: 32001
Synr: 33702
Dcp-1: 37729
Debcl: 53585"
  },
  {
    "caption": "A. Inhibition of Synr  suppresses the wing  defect that is induced by p53, a potent apoptosis inducer. B. Inhibition of Synr  suppresses p53-induced caspase activation. Data information: Statistical significance was determined using a two-tailed unpaired t-test (B), Scale bar, 500 μm in A",
    "ncbi_link": "Synr: 33702
p53: 2768677"
  },
  {
    "caption": "D. Inhibition of Synr  in the midgut enterocytes  enhances resistance to starvation. E. The synr  mutant also exhibits enhanced resistance to starvation. Data information: Statistical significance was determined using a log-rank (Mantel-Cox) test (D-E).",
    "ncbi_link": "synr: 33702
Synr: 33702"
  },
  {
    "caption": "(b) TR3 mutant Flag-ΔNLS but not Flag-NLS promotes the induction of autophagy in response to THPN treatment. The siRNA-resistant versions of Flag-ΔNLS and Flag-NLS were transfected into TR3-knockdown A375 cells. Top, the cells cotransfected with GFP-LC3 were further treated with THPN for 24 h before microscopic analysis (scale bars, 10 μm). Middle, the conversion of LC3-I to LC3-II was analyzed by western blotting. The rate of cell survival was determined after THPN treatment for 48 h (bottom). '-' represents vehicle treatment only.",
    "ncbi_link": "LC3: Q9GZQ8///Q9BXW4///Q9H492///440738///81631///84557
TR3: 3164"
  },
  {
    "caption": "(c) Nix assists the TR3 mitochondrial targeting. Cells with Nix, Pink1 and Bnip3 knockdown were treated with THPN (20 μM, 6 h). Top, mitochondrial TR3 was assayed by western blotting. Nix knockdown abolishes the THPN-induced (20 μM, 24 h) formation of LC3 foci (middle and bottom; scale bars, 10 μm). Images of full blots are shown in Supplementary Figure 7. All of the data are presented as the mean ± s.e.m. of three independent experiments. **P 0.01; NS, not significant; ctrl, control.",
    "ncbi_link": "Bnip3: 664
Nix: 665
Pink1: 65018"
  },
  {
    "caption": "(b) Site C of LBD is critical for Nix binding, as determined by the in vitro pull-down assay. The purified bead-bound GST or GST-Nix proteins were incubated with different mutants as indicated and THPN (20 μM) for 3 h; the proteins were then analyzed by western blotting. IB, immunoblotting.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "(e) DPDO cannot facilitate Nix binding to TR3. Top, the structure of DPDO. Middle, DPDO binding could not form the interacting surface for Nix, unlike THPN. The structures of Arg563 and Ser553 are the same as those in the native structure. Bottom, DPDO does not enhance the interaction between TR3 and Nix. Different plasmids were transfected into A375 cells as indicated, and cells were treated with DPDO (20 μM, 3 h). The TR3 interaction with Nix was determined by co-immunoprecipitation. Images of full blots are shown in Supplementary Figure 7. IP, immunoprecipitation; HA, hemagglutinin.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "(b) Effects of different plasmids on the THPN-induced dissipation of ΔΨm. Top, endogenous TR3 was knocked down by shRNA, and the siRNA-resistant version of TR3, TR3-NLS, TR3-ΔNLS or TAD (Supplementary Fig. 2c) were separately transfected into the cells as indicated. Bottom, similarly, the siRNA-resistant version of Nix or ΔTM were separately transfected into Nix knockdown cells. Transfected cells were treated with THPN (20 μM, 12 h), and their ΔΨm was assessed by flow cytometry. Ctrl, control.",
    "ncbi_link": "Nix: 665
TR3: 3164"
  },
  {
    "caption": "(c) ANT1 and VDAC1 are required for the THPN-induced autophagy. The ANT1 and VDAC1 shRNA-expressing plasmids, which also encoded EGFP for evaluating the transfection efficiency, were separately transfected into cells; mCherry-LC3 was cotransfected to display autophagy. Green cells are those transfected with ANT1 or VDAC1 shRNA, and the cells with red cytoplasmic puncta are autophagic cells (top; scale bars, 10 μm).",
    "ncbi_link": "LC3: 440738///81631///84557
ANT1: 291
VDAC1: 7416"
  },
  {
    "caption": "(d) ANT1 and VDAC1 are required for the THPH-induced dissipation of ΔΨm and cell death. Endogenous ANT1 or VDAC1 was separately knocked down by shRNA, and the dissipation of ΔΨm was determined after THPN (20 μM, 12 h) treatment (left). ANT1 and VDAC1 knockdown abolishes the THPN-induced (20 μM, 48 h) cell death (right). All of the data are presented as the mean ± s.e.m. of three independent experiments. **P 0.01.",
    "ncbi_link": "ANT1: 291
VDAC1: 7416"
  },
  {
    "caption": "(b) Knockdown of Tom40 and Tom70 blocks TR3 transit to MIM. Endogenous Toms were separately knocked down by their corresponding shRNAs, and the TR3 expression of mitochondrial fractions was detected as described above. Ctrl, control.",
    "ncbi_link": "Tom70: 855602
Tom40: 10452"
  },
  {
    "caption": "(c) Tom40 and Tom70 are required for the THPN-associated dissipation of ΔΨm (left), conversion of LC3-I to LC3-II (right and top) and cell death (right and bottom). Endogenous Toms were separately knocked down by the corresponding shRNAs. ΔΨm, LC3-II and cell death were detected as described above. Images of full blots are shown in Supplementary Figure 7.",
    "ncbi_link": "Tom70: 855602
Tom40: 10452"
  },
  {
    "caption": "(d) The mitochondria were markedly eliminated after treatment with THPN for 24 h. Right, endogenous Tom40 and Tom70 were knocked down, and the amount of mitochondria was measured by the fluorescence intensity of Tom20 (green). Left, the volume of mitochondria from five randomly picked regions was quantified by ImageJ software. All of the data are presented as the mean ± s.e.m. of three independent experiments. *P 0.05, **P 0.01, ***P 0.001; NS, not significant.",
    "ncbi_link": "Tom70: 855602
Tom40: 10452"
  },
  {
    "caption": "(a) THPN inhibits the formation of tumors in the liver and lung in a TR3-dependent manner. B16 cells transfected with either control shRNA, TR3 shRNA or ATG7 shRNA (5 × 105) were separately injected into the lateral tail vein of 6-week-old C57BL/6J mice (n = 7). THPN were administered 3 d after inoculation. The tumors formed in the lung and liver are indicated (top; scale bars, 5 mm) and were counted (bottom). Ctrl, control.",
    "ncbi_link": "ATG7: 74244
TR3: 15370"
  },
  {
    "caption": "(b) Crossed Tyr:NRasQ61K;Ink4a/Arf−/−;TR3+/+ and Tyr:NRasQ61K;Ink4a/Arf−/−;TR3−/− mice (n = 12) were treated topically with DMBA to initiate cutaneous melanocytic neoplasms, and mice were treated with THPN as described in Online Methods. The representative images of dorsal melanomas (top) and the tumor numbers (bottom) are presented.",
    "ncbi_link": "Arf: 12578
Ink4a: 12578
TR3: 15370
NRas: 18176"
  },
  {
    "caption": "(c) The survival curves of crossed Tyr:NRasQ61K;Ink4a/Arf−/−;TR3+/+ and Tyr:NRasQ61K;Ink4a/Arf−/−;TR3−/− mice are shown (n > 16).",
    "ncbi_link": "Arf: 12578
Ink4a: 12578
TR3: 15370
NRas: 18176"
  },
  {
    "caption": "(a) Induction of GFP+ dots in differentiated THP-1 cells stably expressing GFP-LC3, left untransfected or transfected for 6 h with poly(dA:dT) (1.5 μg/ml), then exposed to control antibody (Control Ab), antibody to neutralize IL-1β (Anti-IL-1β), dimethyl sulfoxide (DMSO) or 3-MA (5 mM); results are presented as quantification of GFP-LC3+ dots (top) and images of individual cells (middle). Scale bars, 10 μm.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(b) Expression of AIM2 and beclin-1 in cells transfected with control siRNA or siRNA targeting AIM2 or beclin-1; numbers below lanes indicate band intensity (ratio of cells transfected with targeting siRNA to those transfected with control siRNA).",
    "ncbi_link": "AIM2: 9447
beclin-1: 8678"
  },
  {
    "caption": "(c) Induction of GFP+ dots in differentiated THP-1 cells stably expressing GFP-LC3 and treated with various siRNAs (below graph), quantified 6 h after transfection with poly(dA:dT) (+) or no transfection (-).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(d) Immunoblot analysis of the expression of LC3-I and LC3-II (above) in wild-type (WT) and Aim2−/− BMDMs left untransfected or transfected for 6 h with poly(dA:dT); numbers below lanes indicate division of the ratio of induced LC3-I to induced LC3-II by the ratio of basal LC3-I to basal LC3-II (band intensities). Below, immunoblot analysis of IL-1β in supernatants after overnight culture.",
    "ncbi_link": "poly(dA:dT): 
Aim2: 383619"
  },
  {
    "caption": "(e) Immunoblot analysis of LC3-I and LC3-II in or wild-type, ASC-deficient (Pycard-/-; called 'Asc-/-' here) or caspase-1-deficient (Casp1-/-) BMDMs primed with LPS (20 ng/ml) and then left untransfected or transfected with poly(dA:dT) or left untreated or treated with nigericin for 4 h; numbers below lanes as in d. Actin serves as a loading control throughout. NS, not significant; *P 0.05 and **P 0.01 (unpaired t-test). Data are from three individual experiments",
    "ncbi_link": "poly(dA:dT): 
Casp1: 12362
caspase-1: 12362
ASC: 66824
Asc: 66824
Pycard: 66824"
  },
  {
    "caption": "(c) Confocal microscopy of differentiated GFP-LC3+ THP-1 cells sham-transfected with no poly(dA:dT) (Control) or transfected with poly(dA:dT), then fixed and immunostained for ASC (red). Insets (bottom right), 5× enlargement of areas indicated by arrowheads at left. Scale bars, 10 μm (top) or 20 μm (bottom).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(d) Confocal microscopy of differentiated THP-1 cells transfected with poly(dA:dT) and immunostained for LAMP-1 and ASC; below, z-axis projections. Scale bars, 10 μm.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(f) Electron microscopy of differentiated THP-1 cells stimulated with LPS and ATP (left) or transfected with poly(dA:dT) (right) for 2 h and immunostained for ASC, visualized with 15-nm gold-conjugated protein A. Red arrows indicate ASC immunostaining. Right image in each pair, 4.5× enlargement of outlined area at left. Scale bars, 500 nm. Data are representative of three experiments (a,c) or two experiments (b,d-f).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Confocal microscopy of differentiated GFP-LC3+ THP-1 cells left untransfected (Control) or transfected for 2 h with poly(dA:dT) (1.5 μg/ml), then immunostained for endogenous AIM2",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(b) Confocal microscopy of differentiated THP-1 cells transfected for 3 h with poly(dA:dT), then immunostained for LAMP-1 and AIM2.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Immunoblot analysis of AIM2, ASC and LC3-II in lysates of differentiated THP-1 cells left untransfected or transfected with poly(dA:dT) (1.5 μg/ml) and left untreated or treated with 3-MA, rapamycin or amino-acid starvation, then separated into an inflammasome-enriched fraction (top) or an autophagosome-enriched fraction (middle). Bottom, immunoblot analysis of total cell lysates.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Immunoblot analysis of ASC immunoprecipitates (IP; left) and total lysates (right) of differentiated THP-1 cells left untransfected or transfected for 2 h with poly(dA:dT) (1.5 μg/ml), probed for beclin-1 and ASC (below), then stripped and reprobed for p62 (above).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(d) Immunoblot analysis of lysates of cells transfected twice with siRNA with scrambled sequence (−) or siRNA specific for beclin-1 or p62; numbers below lanes indicate band intensity (as in Fig. 1b).",
    "ncbi_link": "beclin-1: 8678
p62: 8878"
  },
  {
    "caption": "(e) Immunoblot analysis of the inflammasome and autophagosome fractions and total lysates of differentiated THP-1 cells transfected as in d, with poly(dA:dT) included in the second transfection; lysates were prepared 4 h after the final transfection.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Immunoblot analysis of ASC immunoprecipitates of differentiated THP-1 cells transfected for 2h with poly(dA:dT) (1.5 μg/ml), probed for ubiquitin (Ub), then stripped and reprobed for K63-linked ubiquitin (Ub-K63), then stripped and reprobed for ASC.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(c) Confocal microscopy of differentiated THP-1 cells transfected for 2 h with poly(dA:dT), immunostained for ASC (red) and polyubiquitin (green). PolyUb, polyubiquitination. Scale bars, 10 μm. Brackets (right margins in a,b) indicate smear of ubiquitinated proteins. Data are representative of three (a,c) or two (b) experiments.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Immunoblot analysis of lysates of human monocytes-macrophages primed with LPS (10 ng) and then transfected with poly(dA:dT) (1.5 μg/ml) or treated with nigericin (4 μM) for 6 h (numbers below lanes as in Fig. 1d).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(b) Immunoblot analysis of processed caspase-1 and IL-1β (top) and enzyme-linked immunosorbent assay of IL-1β (middle) in supernatants of monocytes-macrophages treated for 6 h with various combinations (bottom) of poly(dA:dT) (b) or nigericin (c), plus 3-MA and amino-acid starvation. *P 0.01 (unpaired t test).",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(d) Confocal microscopy of LPS-primed human monocytes-macrophages transfected for 3 h with poly(dA:dT) (top), treated for 3 h with nigericin (middle) or left unstimulated (bottom), immunostained for p62 (green) and ASC (red); arrows indicate colocalized proteins. Second row, three-dimensional volume rendering reconstructed from confocal z-stack images. Scale bars, 10 μm. Data are representative of at least two experiments.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(a) Immunoblot analysis of lysates of LPS (20 ng/ml)-primed mouse BMDMs exposed to LPS (500 ng/ml) and ATP (3 μM), poly(dA:dT) (1.5 μg/ml) or uric acid crystals (50 μg/ml), detecting GTP-bound RalB (collected by RaBP1-agarose affinity purification) and RalB in total lysates.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(b) Immunoblot analysis of lysates and supernatants of mouse BMDMs transfected with control or RalB-specific siRNA on 2 sequential days, then primed with LPS and exposed for 6 h to poly(dA:dT) (1.5 μg/ml), probed for RalB, LC3 and IL-1β; supernatants were collected after overnight culture in serum-free medium (numbers below lanes as in Fig. 1d). Nonsp, nonspecific band.",
    "ncbi_link": "poly(dA:dT): 
RalB: 64143"
  },
  {
    "caption": "(c) Immunoblot analysis of lysates of wild-type and Aim2−/− mouse BMDMs transfected with control or AIM2-specific siRNA on 2 sequential days, primed for 2 h with LPS and then exposed for 1 h to poly(dA:dT) (numbers below lanes as in Fig. 1d).",
    "ncbi_link": "poly(dA:dT): 
Aim2: 383619"
  },
  {
    "caption": "(d) Immunoblot analysis of ASC immunoprecipitates from LPS-primed mouse BMDMs left untreated or transfected for 1 h with poly(dA:dT) and treated for 30 min with LPS and ATP. Mock, immunoprecipitation with control antibody.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "(e) Confocal microscopy of LPS-primed mouse BMDMs left untransfected or transfected for 30 min with poly(dA:dT), immunostained for RalB and AIM2 (left three columns); RalB and ASC (middle columns); and beclin-1 and AIM2 (right two columns). Bottom row, 3× electronic enlargement of areas outlined above. Scale bars, 10 μm. Data are representative of at least two experiments.",
    "ncbi_link": "poly(dA:dT): "
  },
  {
    "caption": "Adult Swiss mice (n = 11 Veh; 15 AβOs) received a single i.c.v. injection of vehicle or 10 pmol AβOs and were assessed in a glucose tolerance test (2 g glucose/kg body weight, i.p.) 7 days after injection. Blood levels of glucose were measured at several time points following glucose administration. Bar graph represents areas under the curves in the time course plot. Data are representative of three independent experiments with similar results. Left panel: ***P = 0.0006, two-way ANOVA followed by Bonferroni post hoc test; right panel: *P = 0.0207, Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Insulin tolerance test (1 IU insulin/kg body weight, i.p.) (n = 7 Veh; 8 AβOs). Blood levels of glucose were measured at several time points following insulin administration. Bar graph represents the kinetic constants for glucose disappearance (Kitt) calculated from the time course plot. Data are representative of two independent experiments with similar results. Left panel: *P = 0.0456 and ***P = 0.0007, two-way ANOVA followed by Bonferroni post hoc test; right panel: **P = 0.0033, Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Glucose tolerance test (2 g glucose/kg body weight, i.p.) in mice 7 days after a single intracaudal (C; n = 8 animals/group) or intraperitoneal (D; n = 13 animals/group) injection of AβOs (10 pmol) or vehicle.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Glucose tolerance test (2 g glucose/kg body weight, i.p.) in 8- to 13-month-old APP/PS1 mice (E; n = 9 animals/group) or 6-month-old 3xTg-AD male mice (F; n = 10 WT; 9 3xTg), or their corresponding wild-type littermates. Bar graph represents areas under the curves in the time course plots. In (E), left panel: *P = 0.0466, two-way ANOVA followed by Bonferroni post hoc test; right panel: &P = 0.072, Student's t-test. In (F), left panel: *P = 0.0171 and #P = 0.0781, two-way ANOVA followed by Bonferroni post hoc test; right panel: *P = 0.0101, Student's t-test.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Epididymal fat mass was analyzed in mice (n = 6 animals/group) 7 days after i.c.v. injection of vehicle or AβOs. Data are representative of three independent experiments with similar results. *P = 0.0255.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Relative expression of leptin (C), TNF-α (D) and IL-6 (E), respectively, in white adipose tissue of mice (n = 7 Veh; 9 AβOs) 7 days after i.c.v. injection of vehicle or AβOs. In (C), *P = 0.0394; in (D), **P = 0.0038; in (E), *P = 0.0305; Student's t-test.",
    "ncbi_link": "Aβ: 351
IL-6: 16193
leptin: 16846
TNF-α: 21926"
  },
  {
    "caption": "p-JNK (F; n = 5 animals/group) and IRS-1pSer312 (G; n = 6 animals/group) levels (normalized by total JNK and total IRS-1, respectively) in skeletal muscle of mice 7 days after i.c.v. injection of vehicle or AβOs. In (F), *P = 0.0464; in (G), *P = 0.0081; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative images of GLUT-4 immunofluorescence in insulin-stimulated skeletal muscle from mice that were i.c.v.-injected with vehicle (Veh) or 10 pmol AβOs. Bar graphs show quantification of GLUT-4 surface immunoreactivity in skeletal muscle of mice that received intraperitoneal injections of PBS or insulin (1 IU/kg body weight) 7 days after i.c.v. injection of vehicle or AβOs, as indicated (n = 5 animals/group). Scale bar = 25 μm. *P = 0.0144, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "GLUT-4 mRNA (n = 4 animals/group) and total protein levels (normalized to actin levels; n = 5 Veh; 6 AβOs) were unchanged in skeletal muscle of Swiss mice injected with vehicle (Veh) or 10 pmol AβOs.",
    "ncbi_link": "Aβ: 351
GLUT-4: 20528"
  },
  {
    "caption": "Plasma levels of insulin (K; n = 12 animals/group), leptin (L; n = 11 Veh; 12 AβOs), cholesterol (M; n = 8 Veh; 6 AβOs), triglycerides (N; n = 8 Veh; 6 AβOs) or noradrenaline (O; n = 7 Veh; 8 AβOs) measured 7 days after i.c.v. injection of vehicle (Veh) or 10 pmol AβOs. In (O), *P = 0.0361, Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative immunocytochemistry images of mature hypothalamic neurons in culture exposed to vehicle (Veh) or AβOs (500 nM) for 3 h. Binding of AβOs was detected using anti-oligomer monoclonal antibody NU4 (red). Neurons were double-labeled using MAP-2 antibody (green). Images represent typical results from experiments with three independent hypothalamic cultures (three coverslips/experimental condition per independent experiment). Scale bar = 30 and 10 μm for main panels and insets, respectively.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative immunocytochemistry image of mature hypothalamic culture exposed to AβOs (500 nM) and immunolabeled with anti-GFAP (green) and NU4 (red) antibodies. Insets show AβOs binding to neuronal dendrites, whereas no binding was detected to GFAP-positive cells.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative DCFfluorescence images from hypothalamic neuronalcultures exposed to vehicle or AβOs (500 nM, 4 h). Insets show optical zoom images of the indicated areas. Scale bars = 100 and 50 μm for main panels and insets, respectively. Graph shows integrated DCFfluorescence intensities (relative units; see Materials and Methods) (n = 3 independent hypothalamic cultures; three wells/experimental condition per experiment; three images acquired per well). Bars represent means ± SEM. #P = 0.0604, one-sample t-test compared with a fixed value of 100 RUs.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "LDH activity (IU/l) in culture media of hypothalamic cultures exposed to vehicle or AβOs (500 nM, 3 h).",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative immunofluorescence images of eIF2α-P in hypothalamic cultures exposed to vehicle or AβOs (500 nM, 3 h) in the absence or presence of infliximab (1 μg/ml). Scale bar = 30 μm. Graph represents integrated immunofluorescence intensities of eIF2α-P levels from three independent hypothalamic cultures (three coverslips/experimental condition per experiment, 20 images per coverslip). Bars represent means ± SEM. *P = 0.0489, one-way ANOVA followed by Bonferroni post hoc test comparing AβO-treated versus vehicle-treated cultures.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative images of hypothalamic cultures exposed to AβOs (500 nM, 3 h) and double-labeled with NU4 (oligomer-sensitive) and eIF2α-P antibodies. Arrow points to a neuron presenting high levels of eIF2α-P in the absence of AβO binding. Nuclear staining (DAPI) is shown in blue. Scale bar = 30 μm.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative images of hypothalamic neurons labeled with NU4 antibody exposed to AβOs (500 nM, 3 h) in the absence or presence of infliximab (1 μg/ml). Similar patterns of AβO binding were observed in both conditions. Scale bar = 20 μm.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Western blot analysis of eIF2α-P levels in the hypothalamus of mice 4 h (A; n = 4 animals/group) or 7 days (B; n = 6 Veh; 5 AβOs) after a single i.c.v. injection of vehicle (Veh) or 10 pmol AβOs. Graphs show densitometric data normalized by total eIF2α levels. *P = 0.0213.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Western blot analysis of ATF4 levels in the hypothalamus of mice 4 h after i.c.v. injection of vehicle (Veh) or 10 pmol AβOs; graph shows densitometric data normalized by β-actin (n = 7 Veh; 8 AβOs). #P = 0.0731; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Western blot analysis of hypothalamic phospho-IKKβ levels in the hypothalamus of mice 4 h (C; n = 6 animals/group) or 7 days (D; n = 4 Veh; 5 AβOs) after i.c.v. injection of vehicle or 10 pmol AβOs. Graphs show densitometric data normalized by total IKKβ levels. In (D), *P = 0.0437; in (E), *P = 0.0444; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Western blot analysis of IκBα (F; n = 6 animals/group) and cytoplasmic phospho-p65-NF-κB (G; n = 4 Veh; 5 AβOs) in the hypothalamus of mice 4 h after i.c.v. injection of vehicle or 10 pmol AβOs. Graphs show densitometric data normalized by actin (F) or total NF-κB levels (G). *P = 0.0207.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Nuclear NF-κB levels in the hypothalamus 6 h after i.c.v. injection of vehicle or 10 pmol AβOs in mice. Graphs show NF-κB levels normalized by nuclear marker, lamin B (n = 6 animals/group). **P = 0.0024; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "IRS-1pSer636 (I; n = 4 animals/group) and pTyr465 (J; n = 6 Veh; 4 AβOs) levels in the hypothalamus 7 days after i.c.v. injection of vehicle or AβOs in mice. Graphs show IRS-1pSer or IRS-1pTyr levels normalized by total IRS-1. In (I), *P = 0.0043; in (J), *P = 0.0275; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Twelve-hour food intake after a single i.c.v. infusion of insulin (200 mU) in mice. Experiment was performed 7 days after i.c.v. injection of vehicle or AβOs (n = 5 PBS; 5 Veh + Insulin; 9 AβOs + Insulin), data are representative of two independent experiments with similar results. ***P < 0.0001, one-way ANOVA followed by Bonferroni post hoc test comparing Veh-Insulin versus PBS groups.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative images of AβO immunoreactivity (detected using anti-oligomer monoclonal antibody NU4) in the hypothalamus of control, sham-operated adult cynomolgus macaques (Sh; n = 3) or macaques that received i.c.v. injections of AβOs (n = 3; see Materials and Methods). Nuclear staining (DAPI) is shown in blue. Insets show optical zoom images of the areas indicated by white dashed rectangles in the main panels. Scale bars = 100 and 20 μm for main panels and insets, respectively.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Representative images showing eIF2α-P (B), phospho-IKKβ (C) and IκBα (D) immunoreactivities in the hypothalamus of cynomolgus macaques that received i.c.v. injections of AβOs or control (sham-operated; Sh) macaques (n = 3 animals/group). Graphs show immunolabeling optical density analysis from three images acquired in the hypothalamus of each macaque (three control versus three AβO-injected animals). In (B), #P = 0.0523; in (C) #P = 0.1123; unpaired Student's t-test with Welch's correction for unequal variances; AβO-injected monkeys compared to sham-operated monkeys. Scale bars = 50 μm",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Accumulated chow intake (normalized by body weight) measured during 7 days following a single i.c.v. injection of vehicle or 10 pmol AβOs in mice (n = 13 Veh; 10 AβOs; data are representative of two independent experiments with similar results). ***P < 0.0001; Student's t-test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Daily body weight measured during 7 days after i.c.v. injection of vehicle or AβOs (n = 7 animals/group; data are representative of two independent experiments with similar results).",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Adult Swiss mice received a single i.c.v. injection of vehicle or 10 pmol AβOs, and hypothalamic levels of mRNA for AgRP (C; n = 6 Veh; 5 AβOs), NPY (D; n = 6 Veh; 5 AβOs) and POMC (E; n = 7 animals/group) were analyzed 7 days after injection. In (C), *P = 0.0191; in (D), *P = 0.0115; Student's t-test.",
    "ncbi_link": "AgRP: 11604
Aβ: 351
NPY: 109648
POMC: 18976"
  },
  {
    "caption": "Swiss mice received a single i.c.v. injection of vehicle (Veh) or 10 pmol AβOs, and their brains were analyzed by Fluorojade staining of degenerating cells 7 days after the injection. Representative images of Fluorojade staining in the hypothalamus of vehicle- or AβO-injected mice (n = 4/group). Scale bar = 100 μm in left panels (top and bottom) and 20 μm in right panels (top and bottom). Positive control (bottom left panel) was the hippocampus of a mouse that received one i.c.v. injection of quinolinic acid (36.8 nmol) and was analyzed 24 h after.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Glucose tolerance test (2 g glucose/kg body weight, i.p.) in mice that received i.c.v. injections of vehicle, vehicle + TUDCA, AβOs or AβOs + TUDCA (when used, TUDCA was administered in 5 i.c.v. injections of 5 μg TUDCA each, before and after oligomer injection; see Materials and Methods. Control groups received injections of saline). Glucose tolerance test (GTT) was performed 7 days after i.c.v. injection of vehicle or AβOs. Bar graph represents areas under the curves (AUC) in the time course plots (n = 15 Veh; 15 AβOs; 10 Veh + TUDCA; 16 AβOs + TUDCA). Data are representative of two independent experiments with similar results. Left panel: **P = 0.0048, **P = 0.003, two-way ANOVA followed by Bonferroni post hoc test; right panel: *P = 0.0384, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Plasma noradrenaline (NA) levels measured 7 days after i.c.v. injection of vehicle, vehicle + TUDCA, AβOs or AβOs + TUDCA in mice (n = 7 animals/group). Data are representative of two independent experiments with similar results. *P = 0.0071, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "Glucose tolerance test (2 g glucose/kg body weight, i.p.) in TNFR1−/− mice or wild-type littermates performed 7 days after i.c.v. injection of vehicle or AβOs. Bar graph represents areas under the curves (AUC) in the time course plots (n = 8 WT + Veh; 7 WT + AβOs; 7 TNFR−/− + Veh; 8 TNFR−/− + AβOs). Left panel: **P = 0.0049, ***P < 0.0001, two-way ANOVA followed by Bonferroni post hoc test; right panel: *P = 0.0001, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "Aβ: 351
TNFR1: 21938///21937"
  },
  {
    "caption": "Western blot analysis of phospho-IKKβ (D; n = 6 WT + Veh; 6 WT + AβOs; 4 TNFR−/− + Veh; 6 TNFR−/− + AβOs) and IRS-1pSer636 levels (E; n = 6 WT + Veh; 5 WT + AβOs; 6 TNFR−/− + Veh; 5 TNFR−/− + AβOs) in the hypothalamus of wild-type (WT) or TNFR1−/− mice 10 days after i.c.v. injection of vehicle or AβOs. Representative images from Western blot experiments were always run on the same gels but represent noncontiguous lanes. In (D), *P = 0.0088, Student's t-test; in (E), *P = 0.0428, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "Aβ: 351
TNFR1: 21938///21937"
  },
  {
    "caption": "Adult Swiss mice pre-treated with minocycline or PBS received a single i.c.v. injection of vehicle or 10 pmol AβOs, and hypothalamic levels of mRNA for AgRP (F; n = 5 Veh; 6 AβOs; 5 Veh + Mino; 4 AβOs + Mino) and NPY (G; n = 14 Veh; 13 AβOs; 8 Veh + Mino; 9 AβOs + Mino) were analyzed 7 days after injection. In (F), *P = 0.0097, one-way ANOVA followed by Bonferroni post hoc test; in (G), *P = 0.0219, one-way ANOVA followed by Bonferroni post hoc test.",
    "ncbi_link": "AgRP: 11604
Aβ: 351
NPY: 109648"
  },
  {
    "caption": "Glucose tolerance test (GTT) in APP/PS1 mice before and after i.c.v. injection of infliximab (0.2 μg daily for 4 days). Bar graph represents areas under the curves (AUC) in the time course plots (n = 9 animals/group). Left panel: *P = 0.0177, two-way ANOVA followed by Bonferroni post hoc test; right panel: *P = 0.0327, paired t-test.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "B. U2OS cells treated with HU in the presence or absence of ATR inhibitor (ATRi) were fractionated and immunoblotted with indicated antibodies. Relative RADX levels on chromatin were quantified and normalized to histone H3. See also Fig EV2A.",
    "ncbi_link": "ATR: 545"
  },
  {
    "caption": "A. Immunoblot analysis of HCT116 cells transfected with indicated RADX siRNAs and RADX knockout cell lines (RADXΔ).",
    "ncbi_link": "RADX: 55086"
  },
  {
    "caption": "A. Replication fork speeds in U2OS or U2OS/GFP-RADX cells transfected with control (−) or RADX(#6) siRNA targeting the 3'UTR and labeled with CldU and IdU as in Fig 3B (bars, mean; n=400 fibers, pooled from two independent experiments, per condition).",
    "ncbi_link": "RADX: 55086"
  },
  {
    "caption": "E. Parental U2OS and derivative lines stably expressing GFP-RADX alleles or all three RPA isoforms at near-endogenous levels (U2OS/Super-RPA) (Fig EV4A) were transfected with control (−) or RADX siRNA. Replication fork speeds were determined as in (A) (bars, mean; n=400 fibers, pooled from two independent experiments, per condition).",
    "ncbi_link": "RADX: 55086"
  },
  {
    "caption": "F. Replication fork speeds in HCT116 cells with indicated genotypes transfected with control (−), RPA1 (0.2 nM concentration [17]) or RAD51 siRNAs (Fig EV4B) and labeled with CldU and IdU as in Fig 3B (bars, mean; n=400 fibers, pooled from two independent experiments, per condition).",
    "ncbi_link": "RAD51: 5888
RPA1: 6117"
  },
  {
    "caption": "F. Clonogenic survival of U2OS cells transfected with indicated siRNAs and subjected to different CPT doses for 24 h (mean±SEM;n=3 independent experiments). LQ (Linear Quadratic) model was fitted to the fractional survival data, using non-linear least square method. Overlap between confidence intervals of the fitting coefficients was used to evaluate the statistical difference between cell survival after siRADX and siCTRL treatment (*No overlap of 95% confidence interval with siCTRL).",
    "ncbi_link": "RADX: 55086"
  },
  {
    "caption": "(B) Violin plots displaying RNA-seq readings by FPKM (normalized Fragments Per Kilobase Million) of chaperones HSPA1A and HSPA1B of human hippocampus samples of demented patients and controls (n = 49,42; unpaired Kolmogorov-Smirnov test; continuous lines: median; dashed lines: quartiles).",
    "ncbi_link": "HSPA1A: 3303
HSPA1B: 3304"
  },
  {
    "caption": "(D) Mean and SEM of mRNA levels of Xbp1s, Bip/Hspa5 and Chop/Ddit3 were determined in dissected hippocampus of i.p. treated mice by quantitative RT-PCR. (n = 3-4 animals/group. One-way ANOVA followed by Tukey's post-test compared tunicamycin treated groups).",
    "ncbi_link": "Chop: 13198
Ddit3: 13198
Bip: 14828
Hspa5: 14828
Xbp1s: 22433"
  },
  {
    "caption": "(E) Animals received bilateral intra-hippocampal injections of 2 μl tunicamcyin (5 mg/mL) or vehicle for 24 h. Graphs indicate mean and s.e.m. of Xbp1s mRNA levels in the hippocampus (n = 3-4 animals/group. One-way ANOVA followed by Tukey's post-test compared tunicamycin treated groups.",
    "ncbi_link": "Xbp1s: 22433"
  },
  {
    "caption": "Young (3-6 months), middle aged (12-14 months) and aged (18-20 months) conditional knockout for IRE1 (IRE1cKO) and their littermates flox/flox control animals (IRE1WT) were evaluated (C) Representative photomicrographs of β-galactosidase staining of hippocampal slices derived from young (3 months), middle-aged (12 months) and aged (22-24 months) of IRE1WT or IRE1cKO animals. Magnification: 20x; scale bar: 200 μm. Arrows indicate β-galactosidase staining.",
    "ncbi_link": "IRE1: 78943"
  },
  {
    "caption": "Young (3-6 months), middle aged (12-14 months) and aged (18-20 months) conditional knockout for IRE1 (IRE1cKO) and their littermates flox/flox control animals (IRE1WT) were evaluated (D) Mean and SEM of percentage of β-galactosidase staining in CA3 region (n = 3-5 animals/group).",
    "ncbi_link": "IRE1: 78943"
  },
  {
    "caption": "(F) Representative confocal images of dendritic spines (arrows) in the CA1 region of middle-aged IRE1WT animals injected with AAV-Mock or AAV-Cre. 60x magnification, (G) Mean and SEM of spine density per μm (n = 3, 3; 4, 4 animals). P computed by unpaired Student's t test within each age-matched group.",
    "ncbi_link": "Cre: 2777477
IRE1: 78943"
  },
  {
    "caption": "(E) Representative images of β-galactosidase staining of hippocampal slices derived from aged (22-24 months) TgXBP1s and WT animals. (F) Mean and SEM of percentage of area stained by β-galactosidase in the hippocampus of aged (20-24 months) TgXBP1s compared to littermate controls.",
    "ncbi_link": "XBP1: 22433"
  },
  {
    "caption": "(D) Left panel: Representative images showing dendritic spines of aged (22-24 months) animals injected with AAV2-eGFP (mock) or with AAV2-XBP1s (arrows indicate dendritic spines). Young animal dendrite is shown for reference. 60x magnification. Scale bar: 5μm. Right panel: Mean and s.e.m. of spine density per μm for indicated experimental groups (n = 24, 53 and 35 dendrites from 3, 5 and 6 animals, respectively",
    "ncbi_link": "eGFP: 
XBP1s: 22433"
  },
  {
    "caption": "(E) Left panel: Representative images of β-galactosidase staining of hippocampal slices derived from aged mice injected with AAV2-Mock or AAV2-XBP1s (arrow indicate β-galactosidase staining). Magnification 20x; scale bar, 200 μm. Right panel: Histograms show mean and s.e.m. of percentage of β-galactosidase-stained area. n = 6, 6; unpaired Student's t test.",
    "ncbi_link": "XBP1s: 22433"
  },
  {
    "caption": "(F) Left panel: Immunofluorescence of γH2aX (red) counterstained with nuclei (blue) comparing aged mice injected with AAV-Mock or AAV-XBP1s. Magnification: 40x; Scale bar: 50μm. Right panel: Histograms show mean and s.e.m. of percentage of γH2A- positive cells; unpaired Student's t test comparing the aged groups ( n = 6, 6 animals/group; unpaired Student's t test).",
    "ncbi_link": "XBP1s: 22433"
  },
  {
    "caption": "C) EMSA results of the binding affinities of CENPC-CT WT, CENPC-CT 3A679-681, and CENPC-CT ∆678-683 to the CENP-A nucleosome.",
    "ncbi_link": "CENPC: 395922"
  },
  {
    "caption": "D) Stable expression of GFP-fused CENPC-CT and its mutants (shown in (B)) in CENP-C knockout chicken DT40 cells. α-Tubulin (Tub) was probed as a loading control. Parental CENP-C knockout cells (parental) were also examined.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "F) Localization of CENP-C in CENP-A knockout DT40 cells stably expressing GFP-fused gCENP-A WT, RG-AA, or ∆RG. Scale bar indicates 10 μm. CENP-C was stained by an anti-CENP-C antibody (red) and DNA was stained by DAPI (blue). CENP-C signals on kinetochores in mitotic cells were quantified in each cell. Bar graph indicates mean ± SD (n = 7; ****, P < 0.0001, unpaired t test, two tailed).",
    "ncbi_link": "CENP-A: 100113359"
  },
  {
    "caption": "D) Stable expression of GFP-fused CENPC-CT and CENPC643-864 (shown in (B)) in CENP-C knockout chicken DT40 cells. α-Tubulin (Tub) was probed as a loading control.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "E) Localization analysis of GFP-fused CENPC-CT and CENPC643-864 lacking the CM upstream region (green) on mitotic chromosomes in CENP-C knockout DT40 cells. CENP-T (red) was used as a centromere marker. DNA was stained using DAPI (blue). Scale bar indicates 10 μm.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "D) All constructs analyzed in (E) were stably expressed in CENP-C knockout cells.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "E) Localization analysis of GFP-fused CENPC-CT, CENPC-CTR656E, and CENPC-CTR655E_R656E (green) on mitotic chromosomes in chicken DT40 cells. DNA was stained using DAPI (blue). Scale bar indicates 10 μm.",
    "ncbi_link": "CENPC: 395922"
  },
  {
    "caption": "A The skeletal (tabialis anterior) muscles from control (Lmna+/+ and Lmna+/-) and Lmna-/- mice were stained for acetylated tubulin (green) and nucleus (blue). The representative images with low and high magnification are shown. The insets are enlarged images for cilia.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "B The kidneys from control and Lmna-/- mice were stained for acetylated tubulin (green) and AQ1 (a marker for the proximal tubules, red). The insets show the cilia of proximal renal tubule cells.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "C The uterus from control and Lmna-/- mice was stained for acetylated tubulin (green) and keratin 8 (red). The insets show the cilia at the stroma of the uterus.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "D The ovary from control and Lmna-/- mice were stained for acetylated tubulin (green) and keratin 8 (red). The insets show the cilia of the granulosa cells in the follicles of the ovary.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "E, F The cilia length (E, n=150-180) and cilia positive cells (F, n ≥ 1197) in each organ from 4-week-old Lmna-/- mice (n=3) and their littermate controls (n=3) were measured.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "A RPE cells were infected with lentiviruses encoding shRNAs specific to lamin A/C (shLamin A/C) or luciferase (shLuc). Exogenous lamin A was re-expressed in the lamin A/C-depleted cells (shLamin A/C-Lamin A). An equal amount of whole cell lysates was analyzed by immunoblotting with antibodies as indicated.",
    "ncbi_link": "Luc: 
luciferase: 
Lamin A: 4000
lamin A: 4000
lamin A/C: 4000
Lamin A/C: 4000"
  },
  {
    "caption": "B The cells were serum-starved for 48 h and stained for acetylated tubulin (green), γ-tubulin (red) and DNA (blue). The depletion of lamin A/C (shLamin A/C) led to impaired ciliogenesis, as manifested by no cilia (inset 1) or short cilia (inset 2). Scale bars, 20 μm or 2 μm (insets).",
    "ncbi_link": "lamin A/C: 4000
Lamin A/C: 4000"
  },
  {
    "caption": "A An equal amount of whole cell lysates from RPE cells or those expressing shLamin A/C or luciferase (shLuc) was analyzed by the immunoblotting with antibodies as indicated.",
    "ncbi_link": "Luc: 
luciferase: 
Lamin A/C: 4000"
  },
  {
    "caption": "RPE cells were infected with lentiviruses expressing shRNAs to nesprin 2 (shNesprine 2, clone #1 and #2) or luciferase (shLuc) as a control. An equal amount of whole cell lysates was analyzed by immunoblotting with antibodies as indicated (B).",
    "ncbi_link": "Luc: 
luciferase: 
Nesprine 2: 23224"
  },
  {
    "caption": "E,F RPE cells expressing shNesprine 2 or shLuc were serum-starved for 32 h and then treated with (+) or without (-) Cyto D for another 16 h. The percentage of the cells with cilia in the total counted cells (E, n ≥ 197) and the length of cilia (F, n ≥ 52) were measured.",
    "ncbi_link": "Luc: 
Nesprine 2: 23224"
  },
  {
    "caption": "A,B RPE cells expressing shRNAs specific to lamin A/C or nesprin 2 (shNesprin 2, clones #1 and #2) were stained for G-actin with DNase I (green). Representative images are shown (A). Scale bars, 20 μm. The proportion of nuclear G-actin fluorescence intensity to the whole cell was measured (B, n ≥ 67).",
    "ncbi_link": "lamin A/C: 4000
Nesprin 2: 23224
nesprin 2: 23224"
  },
  {
    "caption": "C An equal amount of whole cell lysates from RPE cells (control) and those expressing shRNAs to importin 9 (shImportin 9, clones #1 and #2) was analyzed by immunoblotting with antibodies as indicated.",
    "ncbi_link": "Importin 9: "
  },
  {
    "caption": "D-F The cells expressing shRNAs to importin 9 were stained for G-actin (green) and F-actin (red). The representative images are shown (D). Scale bars, 20 μm or 10 μm (insets). The proportion of nuclear G-actin intensity to the whole cell (E, n > 152) and the cell spreading area (F, n ≥ 139) were measured.",
    "ncbi_link": "importin 9: 55705"
  },
  {
    "caption": "G-I RPE cells and those expressing shRNAs to importin 9 were serum-starved for 32 h and then treated with (+) or without (-) Cyto D for another 16 h and then stained for acetylated tubulin (white), pericentrin (green) and F-actin (red). Representative images are shown (G). The left insets show the merged signals of acetylated tubulin and pericentrin. Scale bars, 20 μm or 2 μm (magnified images). The percentage of the cells with cilia (H, n ≥ 385) and the length of cilia (I, n ≥ 111) were measured.",
    "ncbi_link": "importin 9: 55705"
  },
  {
    "caption": "A RPE cells expressing shRNAs specific to luciferase (shLuc.), lamin A/C, or nesprin 2 were grown in the growth medium (+ serum) or serum-starved for 1 h (- serum) and then stained for Arp2 (red), CEP164 (a marker for the mother centriole, green) and acetylated tubulin (white). The representative images are shown. Note that Arp2 was found to localize exclusively at the mother centriole (upper panels) or at the both mother and daughter centrioles (lower panels). Scale bars, 0.5 μm. The percentage of cells with Arp2 localized exclusively at the mother centriole in the total counted cells was measured (n=131-240 cells in each group).",
    "ncbi_link": "Luc: 
luciferase: 
lamin A/C: 4000
nesprin 2: 23224"
  },
  {
    "caption": "A RPE cells expressing shRNAs specific to luciferase (shLuc) or lamin A/C (shLamin A/C) were serum-starved for 48 h and then stained for acetylated tubulin (Ac-tubulin, green) and CEP164 (red). The representative images show that the fluorescence intensity of CEP164 at the mother centriole of cilia-negative (left column) and cilia-positive (right column) basal bodies are similar. The graphs shown are the quantification of CEP164 at cilia-negative basal bodies and cilia-positive basal bodies.",
    "ncbi_link": "Luc: 
luciferase: 
lamin A/C: 4000
Lamin A/C: 4000"
  },
  {
    "caption": "i-m) Mice were treated by intravenous injection of NILV-S/MAR(Mock), LV(CD19CAR) and NILV-S/MAR(CD19CAR)-transduced T cells (8x106 cells/injection) at days 18, 21, 24 after tumor implantation. Tumor growth was monitored by caliper measurements. i-k) Tumor volume of individual mice in each treatment groups are presented. l) The average tumor volume of each treatment group is presented and the values on day 37 were statistically compared (n=12 in LV group, n=9 in NILV-S/MAR group and n=11 in Mock control group). m) The survival of mice is shown as Kaplan-Meier curves.",
    "ncbi_link": "CD19: 930"
  },
  {
    "caption": "(A) The activities (mUnits/g of protein) of the MRC enzymes were determined by spectrophotometric kinetic measurements in WT and ∆4-CYB cells and normalized by the percentage of citrate synthase (CS) activity. Results are expressed as mean ± SD (n=4-6 biological replicates). Unpaired Student's t-test **p=0.0100; ***p=0.0002; ****p<0.0001.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(B) Complex I in gel activity assays (IGA) after Blue-native gel electrophoresis (BNGE) of WT and ∆4-CYB samples solubilized either with 1.6 mg DDM/mg protein or 4 mg digitonin/mg protein. The gels were incubated in the reaction mixture for 1.5 hours (lighter signals in DDM gels) or were left to continue the reaction for 24 hours to obtain darker signals (DDM and Digitonin gels).",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(C) BNGE, Western blot and immunodetection, with anti-NDUFS1 (cI), anti-ATP5A (cV) and anti-SDHB (cII) antibodies, of samples from the WT cybrids and from ∆4-CYB clones E (#17.3E) and B (#17.3B).",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(A) Scatter plot generated from the peptide content analyzed by mass spectrometry in each of the 64 slices excised from BNGE and after quantifying the heavy to light (H/L) and (L/H) ratios in both reciprocal labeling experiments performed with mitochondria isolated from WT and ∆4-CYB cells The logarithmic ratios were calculated using MaxQuant and the statistical significance of the differences for the enrichment or depletion of the proteins were determined with Perseus",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(C) Immunodetection of complex III structural subunits on Western blots of total cell lysates separated by SDS-PAGE, from three independent replicates of WT and ∆4-CYB cells. The graph shows the densitometric quantification of the signals corresponding to each subunit normalized to that of the β-Actin. The mean of the three control (WT) samples was set to 1.0 and all the measurements were referenced to that value. The values plotted in the graphs are the mean ± SD (n=3). 2-way ANOVA with Sidak's multiple comparisons test ****p<0.0001; ***p=0.0007.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(D) Immunodetection of complex I structural subunits on Western blots of total cell lysates separated by SDS-PAGE, from three independent replicates of WT and ∆4-CYB cells. The graph shows the densitometric quantification of the signals corresponding to each subunit normalized to that of the β-Actin. The mean of the three control (WT) samples was set to 1.0 and all the measurements were referenced to that value. The values plotted in the graphs are the mean ± SD (n=3). 2-way ANOVA with Sidak's multiple comparisons test ****p<0.0001; **p=0.0024 (NDUFS3); **p=0.0061 (NDUFB8).",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(E) Immunodetection of complex IV structural subunits on Western blots of total cell lysates separated by SDS-PAGE, from three independent replicates of WT and ∆4-CYB cells. The graph shows the densitometric quantification of the signals corresponding to each subunit normalized to that of the β-Actin. The mean of the three control (WT) samples was set to 1.0 and all the measurements were referenced to that value. The values plotted in the graphs are the mean ± SD (n=3). 2-way ANOVA with Sidak's multiple comparisons test **p=0.0011.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(F) Immunodetection of complex II structural subunits on Western blots of total cell lysates separated by SDS-PAGE, from three independent replicates of WT and ∆4-CYB cells. The graph shows the densitometric quantification of the signals corresponding to each subunit normalized to that of the β-Actin. The mean of the three control (WT) samples was set to 1.0 and all the measurements were referenced to that value. The values plotted in the graphs are the mean ± SD (n=3). 2-way ANOVA with Sidak's multiple comparisons test ****p<0.0001.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(G) Immunodetection of complex V structural subunits on Western blots of total cell lysates separated by SDS-PAGE, from three independent replicates of WT and ∆4-CYB cells. The graph shows the densitometric quantification of the signals corresponding to each subunit normalized to that of the β-Actin. The mean of the three control (WT) samples was set to 1.0 and all the measurements were referenced to that value. The values plotted in the graphs are the mean ± SD (n=3). There were no differences in the steady-state levels of the tested subunits (2-way ANOVA with Sidak's multiple comparisons test).",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(A) Complexome profiles of cIII2 structural subunits generated by analyzing the peptide content in each of the 64 slices in which the gel lanes were excised The graphs plot the relative peptide peak intensities along the lane, setting the maximum to 1.0, vs. the molecular mass calculated using the individual complexes and supercomplexes as the standards to generate a calibration curve. The relative amounts of the proteins between the two cell lines was determined by calculating the H/L ratios of peptides that were present in both WT (blue traces) and ∆4-CYB samples (red traces). The represented values are the mean ± SEM of the two reciprocal labeling experiments.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(B) Second-dimension BNGE of digitonin-solubilized samples from WT and ∆4-CYB cells, western blot and immunodetection of the indicated cIII2 structural subunits with specific antibodies. The immunodetection patterns were equivalent to the complexome profiles.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(A) SDS-PAGE, Western blot an immunodetection, with the indicated specific antibodies, of ∆4-CYB and WT cells expressing HA-tagged versions of UQCRQ and UQCR10 and of cells transduced with the lentiviral expression vector without any cDNA insert (Empty).",
    "ncbi_link": "HA: 
4-CYB: 4519
UQCR10: 29796
UQCRQ: 27089"
  },
  {
    "caption": "(C) BNGE, Western blot and immunodetection, with the monoclonal (M) anti-UQCRQ antibody (Abcam ab110255), of non-transduced ∆4-CYB and WT cells. The mitoplast samples were solubilized with DDM",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(D) Scatter plot generated from the analysis of the logarithmic heavy (H) to light (L) ratios in the x-axis and the reverse in the y-axis, in the two reciprocal labeling SILAC experiments (1 and 2) and anti-HA immunopurification of ∆4-CYB and WT cells expressing UQCR10HA.",
    "ncbi_link": "HA: 
4-CYB: 4519
UQCR10: 29796"
  },
  {
    "caption": "(E) Complexome profiles for the proteins found specifically enriched in ∆4-CYB UQCR10HA, according to the SILAC immunopurification experiments The represented values are the mean ± SEM of the two reciprocal labeling experiments.",
    "ncbi_link": "HA: 
4-CYB: 4519
UQCR10: 29796"
  },
  {
    "caption": "(F) SDS-PAGE, Western blot and immunodetection, with the indicated specific antibodies, of ∆4-CYB and WT cells expressing an HA-tagged version of CYC1 and of cells transduced with the lentiviral expression vector without any cDNA insert (Empty).",
    "ncbi_link": "HA: 
CYC1: 1537
4-CYB: 4519"
  },
  {
    "caption": "(H) Scatter plot generated from the analysis of the logarithmic heavy (H) to light (L) ratios in the x-axis and the reverse in the y-axis, in the two reciprocal labeling SILAC experiments of anti-HA immunopurification of ∆4-CYB and WT cells expressing CYC1HA.",
    "ncbi_link": "HA: 
CYC1: 1537
4-CYB: 4519"
  },
  {
    "caption": "(B) Complexome profiles of the cI assembly factor NDUFAF2 in WT (blue) and ∆4-CYB (red) mitochondria The represented values are the mean ± SEM of the two reciprocal labeling experiments.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(D) Quantification of the area of the N-module peak corresponding to the molecular mass of the fully assembled cI: 1,172 kDa in ∆4-CYB samples and the respirasome (cI+cIII2+cIV) SCs in #4.1 WT samples (2,110 kDa). The plotted values are the mean mean ± SD (n=2). Unpaired Student's t-test ****p<0.0001.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(E) 2D BNGE, Western blot and immunodetection analysis of WT and ∆4-CYB mitochondria from cells collected at the same times after doxycycline treatment to follow the incorporation kinetics of the indicated cI nuclear-encoded subunits, belonging to different structural modules. The blots shown were either exposed for 16 sec. (low exposures) or 160 sec. (high exposures) in order to visualize the qualitative signals in the ∆4-CYB samples.",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(A) SDS-PAGE, Western blot and immunodetection of AOXHA expression in whole-cell lysates from WT and ∆4-CYB cells transduced with the AOXHA/pWPXLd-ires-HygroR lentiviral vector. The transduction and selection controls were the same cell lines transfected with an empty pWPXLd-ires-HygroR vector (EV).",
    "ncbi_link": "HA: 
AOX: 2874947
4-CYB: 4519"
  },
  {
    "caption": "(B) Growth curves of the AOXHA expressing cell lines and their corresponding EV controls. Cell growth was monitored every six hours after substituting the medium in two replicate 24-well plates, one plate with medium without uridine (Uridine-), and the second plate with medium supplemented with 50 µg/ml uridine (Uridine+). The graphs show the average confluence ± SD at each time point (n=6 wells per cell line).",
    "ncbi_link": "HA: 
AOX: 2874947"
  },
  {
    "caption": "(D) 1D BNGE, Western blot and immunodetection analyses of digitonin-solubilized mitochondria from WT and ∆4-CYB cybrids expressing AOXHA and their corresponding EV controls.",
    "ncbi_link": "HA: 
AOX: 2874947
4-CYB: 4519"
  },
  {
    "caption": "(F) Spectrophotometric kinetic measurements of cI activity in WT and ∆4-CYB AOXHA and EV samples, normalized by the percentage of citrate synthase (CS) activity. Results are expressed as mean ± SD (n=5 biological replicates). 2-way ANOVA with Tukey's multiple comparisons test **p=0.0077 (WT AOXHA vs. ∆4-CYB AOXHA); **p=0.0044 (∆4-CYB EV vs. ∆4-CYB AOXHA); ***p=0.0003; ****p<0.0001.",
    "ncbi_link": "HA: 
AOX: 2874947
4-CYB: 4519"
  },
  {
    "caption": "(H) Respirometry analyses , in WT EV controls and AOXHA- expressing cells untreated or treated with 2.5 µM antimycin A for 7 days (+AA). Results are expressed as mean ± SD (n=4 biological replicates). 2-way ANOVA with Tukey's multiple comparisons test ****p<0.0001.",
    "ncbi_link": "AOX: 2874947"
  },
  {
    "caption": "(I) 1D BNGE followed by cI-IGA (right) or Western blot and immunodetection of cIII2 subunit CYC1 (left) in digitonin-solubilized samples from WT EV controls and AOXHA- expressing cells untreated (-) or treated (+) with 2.5 µM antimycin A for 7 days.",
    "ncbi_link": "HA: 
AOX: 2874947"
  },
  {
    "caption": "(D) 1D BNGE, Western blot and immunodetection of two cIV subunits (MT-CO1 and COX7B) in samples from WT and ∆4-CYB cells solubilized with DDM and digitonin (Dig).",
    "ncbi_link": "4-CYB: 4519"
  },
  {
    "caption": "(F) qPCR analysis of ATF3 induction following infection of HeLa cells with Listeria for 1-4 h. Values are means±s.e.m. n=3. Scale bars: 10 μm.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "ATF3: 467"
  },
  {
    "caption": "(A) HeLa cells were infected with Listeria wild‐type (WT) or the LLO/PlcA/PlcB triple knockout (TKO) mutant strain for 0.5-4 h, and lysates were analysed by blotting using indicated antibodies.",
    "ncbi_link": "LLO: 12552412
PlcA: 14021233
PlcB: 14020501"
  },
  {
    "caption": "(B) qPCR analysis of ATF3 and IL‐8 induction following infection of HeLa cells with Listeria WT or TKO for 1-4 h. Values are means±s.e.m. n=3.",
    "ncbi_link": "ATF3: 467
IL‐8: 3576"
  },
  {
    "caption": "(A) qPCR analysis of ATF3 induction following infection of HeLa cells with WT, TKO, PlcA/B− or LLO− Listeria strains for 1-4 h. Values are means±s.e.m. n=3.",
    "ncbi_link": "ATF3: 467
LLO: 12552412
PlcA: 14021233"
  },
  {
    "caption": "(B) HeLa cells were infected with WT, PlcA/B− or LLO− Listeria strains for 0.5-4 h, and lysates were analysed by blotting using indicated antibodies.",
    "ncbi_link": "LLO: 12552412
PlcA: 14021233"
  },
  {
    "caption": "(C) HeLa cells left unstimulated (CTR) or infected with WT, PlcA/B− or LLO− Listeria strains for 1 h, analysed by IF using antibodies against mTOR and LAMP2. The arrow shows a Listeria vacuole positive for mTOR and LAMP2, and arrowheads indicate mTOR‐ and LAMP2‐positive late endosomes or lysosomes.",
    "ncbi_link": "LLO: 12552412
PlcA: 14021233"
  },
  {
    "caption": "(D, E) Percentage of cells infected with WT, PlcA/B− or LLO− Listeria strains displaying one or several LAMP2+ (D) or NDP52+ (E) Listeria vesicles. Values are means±s.e.m. n=3. **P0.01.",
    "ncbi_link": "LLO: 12552412
PlcA: 14021233"
  },
  {
    "caption": "(E) HeLa cells infected with Listeria WT, PlcA/B− or PlcA/B− ectopically expressing PlcA for 3 h, analysed by IF using an antibody against NDP52.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(F, G) Percentage of cells infected for 3 h with Listeria WT, PlcA/B− or PlcA/B− ectopically expressing PlcA displaying one or several NDP52+ granules (F) or bacteria entrapped in NDP52+ autophagosomes (G). Values are means±s.e.m. n=2. Scale bars: 5 μm.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(B) Murine embryonic fibroblasts (MEFs) from WT or ATG16L1‐deficient (ATG16L1 KO) mice infected with Listeria WT for 4 h were analysed by IF using an antibody against ubiquitinated proteins (Ubi).",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "(A) HeLa cells were transfected with GFP‐RFP‐LC3 and either were left uninfected (t=0) or were infected with Listeria WT or PlcA/B− for 1-4 h. GFP+ RFP+ and GFP− RFP+ puncta appear yellow and red, respectively. Percentage of cells infected with Listeria WT or PlcA/B− for 1-4 h displaying GFP− RFP+ red puncta were quantified. Values are means±s.e.m. n=3. **P0.01; ***P0.001.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(B) HeLa cells left unstimulated (CTR) or infected with Listeria WT or PlcA/B− for 4 h were lysed and PI3P levels measured by competitive ELISA.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(D) HeLa cells infected with Listeria PlcA/B− for 3 h, in the absence or presence of Wortmannin added during the last 10 min of infection, analysed by IF using antibodies against NDP52 and WIPI‐2. The arrow indicates an NDP52+ granule. Scale bars: 5 μm.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(A, B) HeLa cells infected for 4 h with Listeria WT expressing GFP (WT GFP), Listeria PlcA/B− expressing mCherry (PlcA/B− mCherry), or both Listeria strains at a 1:1 ratio, were analysed by IF using an antibody against NDP52 (A). (B) Quantification of the percentage of cells displaying NDP52+ PlcA/B− mCherry from the experiments described in (A), in cells infected with either PlcA/B− mCherry alone or WT GFP and PlcA/B−mCherry (co‐infection). Values are means±s.e.m. n=3. **P0.01.",
    "ncbi_link": "PlcA: 14021233"
  },
  {
    "caption": "(C) Murine embryonic fibroblasts (MEFs) from WT or ATG16L1‐deficient (ATG16L1 KO) mice infected for 4 h with WT GFP or Listeria PlcA/B− Listeria, either separately (Single) or in combination (Mix) were lysed and colony forming units (CFUs) determined on agar plates containing appropriate selection markers. Each point represents the value from individual independent experiments. **P0.01; *P0.05. Scale bars: 2.5 μm.",
    "ncbi_link": "ATG16L1: 77040
PlcA: 14021233"
  },
  {
    "caption": "G. Same as E but for the induced levels of either type I IFN (IFNβ1) or type III IFN (IFNλ).",
    "ncbi_link": "IFNβ1: 3456
type I IFN: 3456
type III IFN: 282616///282617
IFNλ: 101180976///282617///282616///282618"
  },
  {
    "caption": "J-M. Percentage of stem cells (OLFM4) goblet cell (FGCBP), mature enterocytes (APOA4) and cells of the enterocyte lineage (FGCBP) from the total organoid cells population (black bar) in mock-treated organoids and after HAstV1 infection. The percentage of infected cells (red bars) and bystander cells (blue bars) within each cell type is shown. The data was obtained from multiplex in situ RNA hybridization in 2D organoids. n=10, mean ± SEM. Statistics show comparison of infected cells between mock-treated, 4h pi and 16h pi organoids. An Ordinary one-way ANOVA and Tukey's multiple comparisons test was used. n.s non significant, * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "APOA4: 337
FGCBP: 8857
OLFM4: 10562"
  },
  {
    "caption": "A. One  image per condition was used to show the multiplex in situ RNA FISH. A representative region of the images was chosen and cropped in order to have a zoom-in of a specific area for better visualization. Shown are the enterocyte lineage marker FABP6 (green), HAstV1 infection (white), and CCL2 gene expression (red) of mock-treated and infected organoids. DAPI is in blue. White arrows show  co-localization of FABP6 and  CCL2 with HAstV1 signal. Scale bar 100µm.",
    "ncbi_link": "CCL2: 6347
FABP6: 2172"
  },
  {
    "caption": "K, Representative co-immunoprecipitation experiments in HEK293T cells that were transfected with GFP-USP42 or the indicated GFP-tagged control, together with the stated Wnt signalling component (N = 3 independent experiments). IgG heavy chain is indicated with an asterisk. Dvl1 functions as a positive control that binds both ZNRF3 and Axin1.",
    "ncbi_link": "Axin1: 8312
Dvl1: 13542
USP42: 84132
ZNRF3: 84133"
  },
  {
    "caption": "E,F, Co-immunoprecipitation experiments in HEK293T cells transfected with the constructs shown in (A). In (F) cells were co-transfected with DVL2 as indicated. Unspecific bands resulting from antibody cross-reaction are marked with asterisks. Representative blots of n ≥ 3 independent experiments are shown.",
    "ncbi_link": "DVL2: 1856"
  },
  {
    "caption": "E,F, qPCR analysis of USP42, LGR5 and AXIN2 expression levels in HCT116 cells. Data are displayed as mean ± SD and show n = 4 (E) or n = 3 (F) independent experiments.",
    "ncbi_link": "AXIN2: 8313
LGR5: 8549
USP42: 84132"
  },
  {
    "caption": "E-H, Immunofluorescence microscopy showing endogenous E-cadherin levels in wt and WLS (Evi) KO HCT116 cells upon transfection with siUSP42 (E), or electroporation with eSpCas9 empty plasmid (non-edited) or eSpCas9-USP42 gRNAs(G). Scale bar = 20 μm. In (F,G), quantification of the fluorescent signal (Alexa-488) in n ≥ 4 biological replicates with n ≥ 15 cells per replicate are shown.",
    "ncbi_link": "Cas9: 
USP42: 84132
Evi: 79971
WLS: 79971"
  },
  {
    "caption": "I-L, Spheroid formation experiments with HCT116 cells upon transfection with siUSP42 (I-K) or electroporation with eSpCas9 empty plasmid (non-edited) or eSpCas9-USP42 gRNAs (L). Scale bar = 500 μm. Where indicated, cells were treated with 5 μM IWP-2 or 20 μM LGK-974 (PORCN inhibitors). The median size was quantified for n ≥ 13 spheroids from a representative experiment repeated independently n ≥ 3 is shown.",
    "ncbi_link": "Cas9: 
USP42: 84132"
  },
  {
    "caption": "A, Representative images of mouse small intestinal organoids generated with empty (Non-edited) or USP42gRNA containing CRISPR-concatemers, and cultured for 3 days in matrigel with the indicated growth factors, or the Wnt secretion inhibitor IWP-2. EN, EGF and noggin. Note that knockout of Usp42 (Usp42 gRNAs) rendered the organoids insensitive to RSPO1 withdrawal. Scale bar = 1 mm.",
    "ncbi_link": "USP42: 76800
Usp42: 76800"
  },
  {
    "caption": "C, qPCR analysis of Lgr5 and Axin2 expression levels in first passage mouse intestinal organoids cultured in EN + 5% RSPO1.",
    "ncbi_link": "Axin2: 12006
Lgr5: 14160"
  },
  {
    "caption": "E) In vitro tumor T cell co-culture competition assay in IFNGR1-KO  D10 cells containing sgRNAs targeting TSC1, TSC2  or both. Statistics was done by Kruskal-Wallis test with Dunn's post hoc test. Error bars indicate SD of four biological replicates with different T cell  donors (n = 4). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "IFNGR1: 3459
TSC1: 7248
TSC2: 7249"
  },
  {
    "caption": "I) In vitro T cell co-culture competition assay of sgCtrl and sgTsc2-expressing lung cancer cell lines. Statistics was done by Mann-Whitney test. Error bars indicate SD of five biological replicates with different T cell  donors (n = 5). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "Tsc2: 7249"
  },
  {
    "caption": "B)  Tumor growth  upon adoptive cell transfer with Ctrl (n = 9) or MART-1 (n = 8) T cells. Data points represent average tumor volume, and error bars represent SEM.",
    "ncbi_link": "MART-1: 2315"
  },
  {
    "caption": "D) Quantification of the  in vivo competition assay (output) at end point by flow cytometry  analysis. Error bars indicate SD. Statistical analysis was performed by Mann-Whitney test. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. For this specific experiment, mice  that deceased before the analysis (n=1, Ctrl T cell  group), with failed ACT injection (n=1, MART-1 T cell  group) or were completely tumor-free after ACT (n=1, MART-1 T cell group) were excluded from the analysis.",
    "ncbi_link": "MART-1: 2315"
  },
  {
    "caption": "A)  Western blot  analysis of baseline mTOR  signaling in sgCtrl- or sgTsc2-expressing melanoma  and lung cancer  cell lines. Representative plot of 2-6 independent experiments. All blots  shown in this panel were run in parallel.",
    "ncbi_link": "mTOR: 2475
Tsc2: 7249"
  },
  {
    "caption": "E) Western blot  analysis of sgCtrl- or sgTSC2-expressing D10 melanoma  cells upon MART-1 T cell challenge for indicated time. Representative of three biological replicates with different T cell donors (n = 3).",
    "ncbi_link": "MART-1: 2315
TSC2: 7249"
  },
  {
    "caption": "F) In vitro competition assay  of sgCtrl- and sgTsc2-expressing D10  cells co-cultured with MART-1 T cells  in the presence of necroptosis (Nec1-s, 20uM) or apoptosis inhibitors (Q-VD-Oph, 50uM), normalized to inhibitor plus Ctrl  T cell-treated groups, showing the net MART-1 T cell  effect. Statistical analysis was performed by one-way ANOVA with Holm-Sidak's multiple comparisons test. Error bars indicate SD of three biological replicates with different T cell  donors (n = 3). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "MART-1: 2315
Tsc2: 7249"
  },
  {
    "caption": "A) Cell viability analysis by CellTiter-Blue assay of sgCtrl- or sgTSC2-expressing D10 melanoma  and A549 lung cancer  cells treated with TRAIL   at indicated concentrations for three days. Statistical analysis was performed by two-tailed unpaired Student t test. For D10, error bars represent SD from three independent experiments (n = 3). For A549, error bars represent SD of pooled data from two independent experiments with three technical replicates each (n = 2). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "C) Flow cytometry analysis of TRAIL-R2  surface expression  level in multiple sgTSC2- expressing tumor cell lines compared to their sgCtrl-expressing controls. Statistical analysis was performed by two-way ANOVA with Sidak's multiple comparisons test. Error bars represent SD of three biological replicates (n = 3). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "D) In vitro competition assay  performed by mixing control and tumor cells with ablation for either TSC2, TRAIL receptors (TNFRSF10A  and TNFRSF10B), or both in a co-culture with MART-1 T cells. Statistical analysis was performed with a one-way ANOVA, followed by a Tukey post-hoc test. Error bars indicate SD of four biological replicates with different T cell donors. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.",
    "ncbi_link": "MART-1: 2315
TNFRSF10A: 8797
TNFRSF10B: 8795
TSC2: 7249"
  },
  {
    "caption": "C) TSC2  immune challenge signature expression  in cohorts of patients  after ICB treatment. Early during treatment (EDT), anti-PD-1 + anti-CTLA-4, and anti-PD-1 alone treatment cohorts. Statistical significance was calculated with Student t test for normally distributed data, or with Mann-Whitney test for non-normally distributed data. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. Partial response and complete response (PRCR) are defined as responder (R); stable disease (SD) and progressive disease (PD) are defined as non-responder (NR).",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "Representative flow cytometric analysis of BAL from Csf2ra-/- recipients 8 weeks after neonatal i.n. transfer of YS EMP from CD45.1+ E10.5 embryos, 8-week old un-transferred Csf2ra-/-, and WT (CD45.2) mice. Pre-gated viable CD45+ singlets.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Numbers of EMP effectively transferred in neonates (white circle) and numbers of EMP-derived AM (red circles) in BAL and lung of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Numbers of EMP-derived AM in the BAL (left) and lung (right) (C) in the BAL of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "total protein in the BAL of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "total eFluor780+ events (E) in the BAL of adult Csf2ra-/- recipients 8 weeks after transfer (n = 5 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis (left) and percentage of donor-derived AM (right) in the BAL and lung from Csf2ra-/- recipients 8 weeks after neonatal transfer of 1:1:1 mixture with E17.5 fetal liver (FeLi) monocytes (Mo) (CD45.1+), E14.5 FeLi Mo (CD45.1+CD45.2+), and E10.5 YS EMP (CD45.2+) (F) or E17.5 fetal lung (FeLu) Mo (CD45.1+), E14.5 FeLu Mo (CD45.1+CD45.2+), and E10.5 YS EMP (CD45.2+) (G) (n = 3 mice).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis (left) and percentage of donor-derived AM (right) in the BAL (top) and lung (bottom) from Csf2ra-/- recipients 10 weeks after neonatal transfer of 1:1 mixture with CD45.1+ E14.5 FeLi Mo and CD45.2+ E14.5 FeLi pMΦ (Group 1) or CD45.1+ E14.5 FeLi pMΦ and CD45.2+ FeLi Mo (Group 2) (n = 3 mice). The expansion fold of donor cells in Csf2ra-/- recipients 10 weeks after neonatal transfer of cells described above in A (n = 3 mice).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis (left) and percentage of donor-derived AM (right) of BAL and lung from Csf2ra-/- recipients 8 weeks after neonatal transfer of 1:1:1 mixture with CD45.1+ E17.5 FeLi pMΦ, CD45.1+CD45.2+ E14.5 FeLi pMΦ, and CD45.2+ E10.5 YS pMΦ (n = 3 mice). Total numbers of donor-derived AM in the BAL and lung of adult Csf2ra-/- recipients 8 weeks after transfer of cells described above in C (n = 3 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis (left) and percentage of donor-derived AM (right) of BAL and lung from Csf2ra-/- recipients 8 weeks after neonatal transfer of 1:1:1 mixture with CD45.1+ E17.5 FeLu pMΦ, CD45.1+CD45.2+ E14.5 FeLu pMΦ, and CD45.2+ E10.5 YS pMΦ (n = 3 mice). Total numbers of donor-derived AM in the BAL and lung of adult Csf2ra-/- recipients 8 weeks after transfer of cells described above in E (n = 3 mice). Age-matched Csf2ra-/- (KO) (n = 3 mice) and WT (n = 3 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis (left) and percentage of donor-derived AM (right) in the BAL and lung from Csf2ra-/- recipients 7 weeks after neonatal transfer of 1:1 mixture with CD45.1+ E14.5 FeLi Mo from WT embryos and CD45.2+ E14.5 FeLi pMΦ from Myb-/- (G) or Myb+/+ (H) embryos (n = 3 mice).",
    "ncbi_link": "Csf2ra: 12982
Myb: 17863"
  },
  {
    "caption": "Representative flow cytometric analysis of BAL from Csf2ra-/- recipients 7 weeks after neonatal i.n. transfer of pMΦ or fetal Mo from CD45.1+ E14.5 fetal livers, 7-week old un-transferred Csf2ra-/-, WT (CD45.2) mice. Pre-gated viable CD45+ singlets.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Numbers of donor-derived AM in the BAL (left) and lung (right) of adult Csf2ra-/- recipients 7 weeks (B) or 1 year (C) after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Total protein in the BAL of adult Csf2ra-/- recipients 7 weeks after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "total eFluor780+ events in the BAL of adult Csf2ra-/- recipients 7 weeks after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Total protein in the BAL of adult Csf2ra-/- recipients 1 year (F, G) after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "total eFluor780+ events in the BAL of adult Csf2ra-/- recipients 1 year (F, G) after neonatal transfer of cells described in A (n = 7 mice). Age-matched Csf2ra-/- (KO) (n = 5 mice) and WT (n = 4 mice) were included as negative and positive controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Body weight measurement of influenza virus (20 pfu of PR8 strain)-infected Csf2ra-/- recipients 24 weeks after neonatal transfer of pMΦ or fetal Mo from E14.5 fetal livers (n = 7 mice from each transferred group), 24-week old un-transferred Csf2ra-/- (n = 5), and WT (n = 8).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "temperature (B) measurement of influenza virus (20 pfu of PR8 strain)-infected Csf2ra-/- recipients 24 weeks after neonatal transfer of pMΦ or fetal Mo from E14.5 fetal livers (n = 7 mice from each transferred group), 24-week old un-transferred Csf2ra-/- (n = 5), and WT (n = 8).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Oxygen (O2) saturation in influenza-infected mice described in A, B 7 days post-infection (p.i.) (n = 5 mice from Csf2ra-/- group; n = 7 mice from each transferred group; n=8 from WT group).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Survival curve of influenza-infected mice described in A, B (n = 5 mice from Csf2ra-/- group; n = 7 mice from each transferred group; n=8 from WT group).",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "Representative flow cytometric analysis of Csf2ra expressions on pMΦ- and fetal Mo-derived AM in Csf2ra-/- recipients 4 weeks after transfer of pMΦ or fetal Mo from E14.5 fetal livers. AM from 4-week old WT mice were included as controls.",
    "ncbi_link": "Csf2ra: 12982"
  },
  {
    "caption": "qPCR (n = 3 biological replicates) analysis of Myb, Maf, Mafb, and Pparg expression in different fetal precursors from WT embryos and mature AM from WT adult mice.",
    "ncbi_link": "Maf: 17132
Mafb: 16658
Myb: 17863
Pparg: 19016"
  },
  {
    "caption": "RNA-seq (C, n = 2 biological replicates) analysis of Eno1, Slc2a6, Txn1, and Txnip gene expression in pMΦ and fetal Mo from E14.5 WT fetal liver.",
    "ncbi_link": "Eno1: 13806
Slc2a6: 227659
Txn1: 22166
Txnip: 56338"
  },
  {
    "caption": "qPCR (D, n = 3 biological replicates) analysis of Eno1, Slc2a6, Txn1, and Txnip gene expression in pMΦ and fetal Mo from E14.5 WT fetal liver.",
    "ncbi_link": "Eno1: 13806
Slc2a6: 227659
Txn1: 22166
Txnip: 56338"
  },
  {
    "caption": "The gene expression patterns of ACE2 of all detected cell types in kidney.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "d, LC3 translocation to the phagosome is induced by TLR signalling. GFP-LC3 was transiently transfected into wild-type or Tlr2-/- macrophages, which were exposed to zymosan for 45 min.",
    "ncbi_link": "Tlr2: 24088"
  },
  {
    "caption": "e, The percentage of phagosomes (n ≥ 50 per group) with GFP-LC3 in wild-type and Tlr2-/- macrophages. Means and ranges are shown (4 mice per group were used).",
    "ncbi_link": "Tlr2: 24088"
  },
  {
    "caption": "a, RAW cells expressing GFP-LC3 were transfected by electroporation with control or Atg5 siRNA oligonucleotides. At 24 h after transfection, cells were fed with zymosan (yellow arrows) and the internalization process was followed by time-lapse video microscopy. Images obtained at 5 and 30 min after zymosan engulfment are shown. b, The percentage of GFP-LC3-associated phagosomes (n ≥ 100 per /group) was obtained from three independent time-lapse videos (2 h each) of macrophages transfected with control or Atg5 siRNA (means and ranges are shown).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, d, Knockdown of ATG5 reduced zymosan-induced GFP-LC3 translocation and lysosomal fusion.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "e, Primary macrophages from wild-type (white bars) and Atg7-null mice (grey bars) were fed live yeast for 1 h and washed. Internalized yeast were extracted from the macrophages at 4 h and 8 h after re-plating. Means and ranges from six different measurements using two mice per group are shown.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "Real-time PCR analysis for the expression levels of ALDH1A1 and ALDH1A2 during the culture activation of HSCs. The PCR data are expressed as the percentage of HSCs-d3. **P-value, paired t-test (n = 3) (compared to HSCs-d3), ALDH1A1/HSCs-P3: 0.003, ALDH1A2/HSCs-P1: 0.0018, ALDH1A2/HSCs-P3: 0.001.",
    "ncbi_link": "ALDH1A1: 24188
ALDH1A2: 116676"
  },
  {
    "caption": "Effect of ALDH1A suppression on HSC activation. HSCs-P1 were transfected with non-targeting siRNA or siRNA specific to ALDH1A1 and/or ALDH1A2, and after 48 h, whole-cell lysates were subjected to Western blotting. **P = 0.0023, paired t-test (n = 3) (siRNA-ALDH1A1/2 compared to control).",
    "ncbi_link": "ALDH1A1: 24188
ALDH1A2: 116676"
  },
  {
    "caption": "Reverse-phase HPLC analysis of whole-cell lysates from the siRNA-ALDH1A-treated HSCs in (E). Typical chromatograms of all-trans retinoic acid and 13-cis retinoic acid. The retention time is 14 min for 13-cis-RA and 23 min for all-trans RA.",
    "ncbi_link": "ALDH1A: 116676///24188"
  },
  {
    "caption": "Albumin and R-III downregulate RA signaling. HSCs-P1 were either transfected with RARE Cignal reporter and expression plasmid containing vehicle or albumin (left panel) or treated with R-III (25-250 nM) after transfection with RARE Cignal reporter (right panel). After 36 h, the transfected cells were harvested for luciferase assay. Renilla luciferase activity was normalized to firefly luciferase activity. Ratios were normalized against the cells transfected with vehicle plasmid. **P-value, two-sample t-test (n = 9) (compared to control), albumin: 0.0037, R-III 125 nM: 0.0032.",
    "ncbi_link": "firefly: 
Renilla: "
  },
  {
    "caption": "Phenotypic changes of HSCs by the expression of albumin and/or ALDH1A. HSCs-P1 were transfected with plasmids encoding albumin, ALDH1A1, and ALDH1A2, either individually or in combination, and incubated in the presence of all-trans retinoic acid (50 nM) for 18 h. Cells were analyzed by oil red O staining. Scale bar, 20 μm.",
    "ncbi_link": "albumin: 24186
ALDH1A1: 24188
ALDH1A2: 116676"
  },
  {
    "caption": "Western blot analysis of cell lysates from albumin- and/or ALDH1A-transfected HSCs as in (B). **P = 0.002, paired t-test (n = 3) (albumin compared to control).",
    "ncbi_link": "albumin: 24186
ALDH1A: 116676///24188"
  },
  {
    "caption": "Reverse-phase HPLC analysis of whole-cell lysates from albumin- and/or ALDH1A-transfected HSCs as in (B).",
    "ncbi_link": "albumin: 24186
ALDH1A: 116676///24188"
  },
  {
    "caption": "Real-time PCR analysis for the expression level of STRA6 during the culture activation of HSCs. The PCR data are expressed as the percentage of HSCs-3d. **P-value, paired t-test (n = 3) (compared to HSCs-d3), HSCs-P2: 0.002, HSCs-P3: 0.0022.",
    "ncbi_link": "STRA6: 363071"
  },
  {
    "caption": "STRA6-mediated uptake of R-III. HSCs-P1 were transfected with non-targeting siRNA or one of the two different STRA6-specific siRNAs, and after 48 h, cells were incubated with R-III for 30 min and analyzed by Western blotting.",
    "ncbi_link": "STRA6: 363071"
  },
  {
    "caption": "(E) zipper RNAi clones (zip iR, in red) in Arm::GFP expressing anchored and stretched third instar wing disc; lower panel shows color coded cell aspect ratio in anchored and stretched discs (bright colors indicate high elongation); zip RNAi clone is outlined in white.",
    "ncbi_link": "GFP: 
Arm: 31151
zipper: 38001
zip: 38001"
  },
  {
    "caption": "(F) Box plot showing distribution of cell aspect ratio for control (wild-type) and zipper RNAi cells in anchored and stretched (20 min) wing disc; median represented by horizontal line, 75th and 25th centiles are represented by top and bottom of the boxes respectively; n=8 wing discs.",
    "ncbi_link": "zipper: 38001"
  },
  {
    "caption": "(G) Color-coded aspect ratio in control and zip RNAi cells (zip RNAi clone outlined in white) subjected to anchoring, stretching (20 min) and relaxation (10 min, post stretch).",
    "ncbi_link": "zip: 38001"
  },
  {
    "caption": "(H) Box plot showing distribution of cell aspect ratio in anchored, stretched (20 min) and relaxed (10 min) wing disc for control (wild-type) and zipper RNAi cells; median represented by horizontal line; 75th and 25th centiles are represented by top and bottom of the boxes respectively, n=3 wing discs.",
    "ncbi_link": "zipper: 38001"
  },
  {
    "caption": "(I) zip-RNAi clone in Arm::GFP wing disc at the beginning (5 min) and at the end (40 min) of stretching experiment. Yellow and red arrows indicate the control and zip RNAi cells respectively.",
    "ncbi_link": "GFP: 
Arm: 31151
zip: 38001"
  },
  {
    "caption": "(J) Change of zip-RNAi aspect ratio (a.r.) relative to change in control cells aspect ratio (a.r.) in the course of stretch, blue line shows fitted regression; dotted line represents 95% confidence bounds of the best fit line; n=3 wing discs.",
    "ncbi_link": "zip: 38001"
  },
  {
    "caption": "discs.\u2028(B) Drok2 mitotic clones (RFP-) in Sqh::GFP third instar imaginal disc. Inset demonstrates Sqh::GFP polarity inside Drok2 clone.",
    "ncbi_link": "rok: 43916"
  },
  {
    "caption": "(C) Sqh::GFP, enGal4>UAS-rok RNAi, UAS-Act5CRFP discs subjected to stretching; inset demonstrates Sqh::GFP polarity in rok RNAi cells (marked by red.",
    "ncbi_link": "Gal4: 
UAS: 
en: 36240
rok: 43916"
  },
  {
    "caption": "(D) zip RNAi clones (labeled as zip iR, indicated in red) in stretched third instar RokK116a::Venus discs.",
    "ncbi_link": "zip: 38001"
  },
  {
    "caption": "(A) Discs expressing Sqh::GFP and enGal4>UAS-dia RNAi, UAS-Act5c-RFP that were stretched; UAS-Act5C::RFP marks dia iR (posterior side) in red. (A\") Insets comparing Sqh::GFP polarity in stretchedenGal4>dia iR, UAS- Act5c-RFP discs; panel 1 refers to anterior (ctrl) side; panel 2 refers to posterior (dia iR) side. ",
    "ncbi_link": "Gal4: 
UAS: 
dia: 35340
en: 36240"
  },
  {
    "caption": "(B) Tissue marked with E-cad::GFP and Sqh::mCherry, expressing dia-RNAi (dia iR) with hhGal4 driver and subjected to stretching. Dotted line indicates anterior-posterior (A-P) compartment boundary. (B\") Inset demonstrates lack of Sqh::GFP polarity in dia-RNAi cells. ",
    "ncbi_link": "Gal4: 
dia: 35340
hh: 42737"
  },
  {
    "caption": "(E) Stretched discs expressing Sqh::GFP and enGal4>UAS-cofilin (upper panel) or UAS-AIP1 (lower panel) RNAi and UAS-Act5c-RFP (marks posterior side in red).\u2028(E\"), Insets comparing Sqh::GFP polarity in stretched discs described in (E); panel 1 refers to anterior (ctrl) side; panel 2 refers to posterior (dia iR) side.",
    "ncbi_link": "AIP1: 
cofilin: 
Gal4: 
UAS: 
dia: 35340
en: 36240"
  },
  {
    "caption": "(F) Sqh::GFP polarity in enGal4> dia iR, UAS-Act5C::RFP discs labeled with Phalloidin-647; Inset (Phall-647) zooms in on cell shape in anterior and posterior disc compartments.",
    "ncbi_link": "Gal4: 
UAS: 
dia: 35340
en: 36240"
  },
  {
    "caption": "(G) Discs expressing nubGal4 and Cd8::GFP (control) or dia iR (KK) labeled with DAPI; ellipse is fitted into the pouch region (red dotted line) and aspect ratio determined as long ellipse axis (b) divided by short ellipse axis (a) (white lines).",
    "ncbi_link": "Gal4: 
dia: 35340
nub: 34669
Cd8: 5740521"
  },
  {
    "caption": "(H) Box plot showing distribution of wing disc pouch aspect ratios in conditions described in (G), n=19 (ctrl) and 16 (dia iR) wing pouches; horizontal line indicates median.",
    "ncbi_link": "dia: 35340"
  },
  {
    "caption": "SMC4 was depleted in G1 through the addition of 5-Ph-IAA 1 h before the final release into S phase such that cells progressed through S and G2 phase in the absence of condensins. NIPBL was depleted in G2 phase after completion of DNA  replication to avoid potential effects of NIPBL depletion on cohesion establishment. B, Representative images from wild type prometaphase cells labelled on one or two sister chromatids as indicated. C, Representative images from wild type G2 cells labelled on one or two sister chromatids as indicated. D, Quantification of sister chromatid separation in one-sister labelled prometaphase cells for experimental conditions as indicated. Dots represent individual cells; red bars indicate the mean. Wild type (n = 83 cells), ΔSMC4 (n = 75 cells) and ΔNIPBL (n = 48 cells) were analysed. Significance was tested using a two-tailed Mann Whitney U test; P = 2.33 x 10-27. Two-sister labelled wild type prometaphase (n = 4), one-sister labelled wild type prometaphase (n = 6), ΔSMC4 prometaphase (n = 4), ΔNIPBL prometaphase (n = 3), wild type G2 (n = 4), ΔSMC4 G2 (n = 3), ΔNIPBL G2 (n = 5). Technical replicates Two-sister labelled wild type prometaphase (n = 9), one sister-labelled wild type prometaphase (n = 14), ΔSMC4 prometaphase (n = 9), ΔNIPBL prometaphase (n = 6), wild type G2 (n = 8), ΔSMC4 G2 (n = 5), ΔNIPBL G2  (n = 8). All images show single Z-slices from 3D-stacks. Yellow boxes indicate inset regions. Scale bars large panels: 5 μm, insets: 1 μ",
    "ncbi_link": "NIPBL: 25836
SMC4: 10051"
  },
  {
    "caption": "SMC4 was depleted in G1 through the addition of 5-Ph-IAA 1 h before the final release into S phase such that cells progressed through S and G2 phase in the absence of condensins. NIPBL was depleted in G2 phase after completion of DNA replication to avoid potential effects of NIPBL depletion on cohesion establishment. F, Representative images from ΔSMC4 prometaphase cells labelled on one sister chromatid. G, Representative images from ΔSMC4 G2 cells labelled on one sister chromatid. H, Representative images from ΔNIPBL prometaphase cells labelled on one sister chromatid. I, Representative images from ΔNIPBL G2 cells labelled on one sister chromatid. Two-sister labelled , ΔSMC4 prometaphase (n = 4), ΔNIPBL prometaphase (n = 3) , ΔSMC4 G2 (n = 3), ΔNIPBL G2 (n = 5). Technical replicates: Two-sister labelled , ΔSMC4 prometaphase (n = 9), ΔNIPBL prometaphase (n = 6) , ΔSMC4 G2 (n = 5), ΔNIPBL G2 (n = 8).",
    "ncbi_link": "NIPBL: 25836
SMC4: 10051"
  },
  {
    "caption": "WAPL was depleted in G2 phase after completion of DNA replication to avoid potential effects of WAPL depletion on cohesion establishment. One sister chromatid was labelled per chromosome as in Fig. 1 SCC1 (WAPL-dTAG cells) was visualised by immunofluorescence. A, Representative images of control WAPL-dTAG cells synchronised to G2 by RO-3306. B, Representative images of ΔWAPL cells synchronised to G2 by RO-3306. C, Representative images of ΔSororin cells synchronised to G2 by RO-3306. D, Quantification of sister chromatid separation as in Fig. 1D Control WAPL-dTAG G2 (n = 36 cells), ΔWAPL G2 (n = 53 cells) and ΔSororin G2 (n = 45 cells) cells were analysed. Dots represent individual cells; red bars indicate the mean. Significance was tested using a two-tailed Mann Whitney U test; P = 3.89 x 10-11 (Control G2, ΔWAPL G2), P = 5.90 x 10-7 (Control G2, ΔSororin G2), P = 2.75 x 10-3 (ΔWAPL G2, ΔSororin G2). Biological replicates: Control WAPL-dTAG G2 (n = 3), ΔWAPL G2 (n = 3), ΔSororin G2 (n = 3), ΔWAPL ΔSororin G2 (n = 3), wild type late prophase (n = 4). Technical replicates Control WAPL-dTAG G2 (n = 6), ΔWAPL G2 (n = 6), ΔSororin G2 (n = 6), ΔWAPL ΔSororin G2 (n = 6), wild type late prophase (n = 7). All images show single Z-slices from 3D-stacks. Yellow boxes indicate inset regions. To aid visualisation, the SCC1 channel is not contrast matched. Scale bars large panels: 5 μm, insets: 2 μ",
    "ncbi_link": "Sororin: 113130
WAPL: 23063"
  },
  {
    "caption": "WAPL was depleted in G2 phase after completion of DNA replication to avoid potential effects of WAPL depletion on cohesion establishment. One sister chromatid was labelled per chromosome as in Fig. 1 and SMC4 (wild type late prophase cells) or SCC1 (WAPL-dTAG cells) was visualised by immunofluorescence. E, Representative images of ΔWAPL ΔSororin cells synchronised to G2 by RO-3306. F, Representative images of wild type cells synchronised to late prophase by release from a RO-3306-mediated G2 arrest. G, Quantification of sister chromatid separation as in Fig. 1D, E. ΔWAPL ΔSororin G2 cells (n = 51 cells) and wild type late prophase (n = 55 cells) cells were analysed. Dots represent individual cells; red bars indicate the mean. Biological replicates: Control WAPL-dTAG G2 (n = 3), ΔWAPL G2 (n = 3), ΔSororin G2 (n = 3), ΔWAPL ΔSororin G2 (n = 3), wild type late prophase (n = 4). Technical replicates Control WAPL-dTAG G2 (n = 6), ΔWAPL G2 (n = 6), ΔSororin G2 (n = 6), ΔWAPL ΔSororin G2 (n = 6), wild type late prophase (n = 7). All images show single Z-slices from 3D-stacks. Yellow boxes indicate inset regions. To aid visualisation, the SCC1 channel is not contrast matched. Scale bars large panels: 5 μm, insets: 2 μm.",
    "ncbi_link": "Sororin: 113130
WAPL: 23063"
  },
  {
    "caption": "A-C, Analysis of sister DNA and SMC protein complex distribution in cross sections perpendicular to the long chromosome axis, as shown in Fig. 2B, E, F. Density of Hoechst minus F-ara-EdU was calculated by subtracting F-ara-EdU fluorescence from Hoechst fluorescence. Line profiles indicate the mean curves of individual line profile measurements aligned to the midpoint between two SMC4 peaks (wild type late prophase), the SCC1 peak (ΔWAPL G2 cells), or the midpoint between two SCC1 peaks (ΔWAPL ΔSororin G2 cells). A, Lines from wild type late prophase (n = 157 lines from 31 cells). B, ΔWAPL G2 cells (n = 110 lines from 18 cells). C, ΔWAPL ΔSororin G2 cells (n = 138 lines from 18 cells) were analysed. Wild type late prophase (n = 4), ΔWAPL G2 (n = 3), ΔWAPL ΔSororin G2 (n = 3). Technical replicates: Wild type late prophase (n = 7), ΔWAPL G2 (n = 6), ΔWAPL ΔSororin G2 (n = 5). Scale bars: 2μm.",
    "ncbi_link": "Sororin: 113130
WAPL: 23063"
  },
  {
    "caption": "A, Representative images of one-sister labelled sister chromatids from ΔWAPL, ΔSMC4 ΔWAPL, or ΔSMC4 ΔWAPL ΔSororin prometaphase cells, as indicated. SMC4 was depleted in G1 through the addition of 5-Ph-IAA 1 h before the final release into S phase such that cells progressed through S and G2 phase in the absence of condensins. WAPL was depleted in G2 phase after completion of DNA replication to avoid potential effects of WAPL depletion on cohesion establishment. B, Quantification of sister chromatid separation as in Fig. 1D, E. ΔWAPL (n = 21 cells), ΔWAPL ΔSMC4 (n = 25 cells), and ΔWAPL ΔSMC4 ΔSororin (n = 28 cells) prometaphase cells were analysed. Dots represent individual cells; red bars indicate the mean. Significance was tested using a two-tailed Mann Whitney U test; P = 6.57 x 10-8 (ΔWAPL); P = 3.64 x 10-7 (ΔWAPL ΔSMC4 ΔSororin). Biological replicates , ΔWAPL prometaphase (n = 3), ΔWAPL ΔSMC4 prometaphase (n = 3), ΔWAPL ΔSMC4 ΔSororin prometaphase (n = 3).",
    "ncbi_link": "Sororin: 113130
SMC4: 10051
WAPL: 23063"
  },
  {
    "caption": "C, Representative images of control prometaphase cells labelled on one sister chromatid and depleted of SMC4 for different amounts of time as indicated. SMC4 was visualised by immunofluorescence using an anti-SMC4 antibody. Cells were synchronised to G2 phase by RO-3306, before being arrested in prometaphase by STLC for 60 min. SMC4 was then depleted through the addition of 1 μM 5-Ph-IAA for 120 or 240 minutes, as indicated. Control (n = 2), ΔSMC4 120 min (n = 2), ΔSMC4 240 min (n = 2). All images show single Z-slices from 3D-stacks. Yellow boxes indicate inset regions. Scale bars large panels: 5 μm, insets: 1 μm.",
    "ncbi_link": "SMC4: 10051"
  },
  {
    "caption": "C, Genomic resolution analysis for G2 cells. Wild type, ΔNIPBL, ΔSMC4, ΔWAPL, ΔSororin, and ΔWAPL ΔSororin cells were analysed. Points indicate the values calculated for each replicate, bars indicate the mean and error bars indicate the standard deviation. Significance was tested using a two-tailed Mann Whitney U test; P = 1.24 x 10-4 (ΔNIPBL G2); P = 1.62 x 10-4 (ΔWAPL G2); P = 5.49 x 10-3 (ΔSororin G2), P = 1.47 x 10-3 (ΔWAPL ΔSororin G2). C, Wild type G2 (n = 11), ΔNIPBL G2 (n = 10), ΔSMC4 G2 (n = 4), ΔWAPL G2 (n = 6), ΔSororin G2 (n = 3), ΔWAPL ΔSororin G2 (n = 4).",
    "ncbi_link": "Sororin: 113130
NIPBL: 25836
SMC4: 10051
WAPL: 23063"
  },
  {
    "caption": "MEFs from δWD and littermate control mice were incubated with HBSS, chloroquine or monensin for 2 h as indicated and cell lysates analysed by western blot for ATG16L1, δWD and LC3 as indicated. Control MEFS express α and β isoforms of ATG16L1 at 70 kDa, and MEFs from δWD mice express a truncated ATG16L1 at 30kDa. (D) shows the level of conversion of LC3 to LC3II estimated by densitometry from a mean (±SD) of three replicate blots.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "A-D. Bone marrow from wild-type (Atg16L1+/+) was used to reconstitute irradiated littermate control mice (B6 WT → control [●] ) or δWD mice (B6 WT → δWD [○] ). Bone marrow from δWD mice was used to reconstitute irradiated δWD mice (δWD → δWD [▲] ). After 12 weeks, mice (n = 5 per group) were challenged with IAV X31 (103 pfu). (A) Mice were monitored for weight loss at indicated time-points.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "Bone marrow from wild-type (Atg16L1+/+) was used to reconstitute irradiated littermate control mice (B6 WT → control [●] ) or δWD mice (B6 WT → δWD [○] ). Bone marrow from δWD mice was used to reconstitute irradiated δWD mice (δWD → δWD [▲] ). After 12 weeks, mice (n = 5 per group) were challenged with IAV X31 (103 pfu). (B) Survival was assessed at indicated time points.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "Bone marrow from wild-type (Atg16L1+/+) was used to reconstitute irradiated littermate control mice (B6 WT → control [●] ) or δWD mice (B6 WT → δWD [○] ). Bone marrow from δWD mice was used to reconstitute irradiated δWD mice (δWD → δWD [▲] ). After 12 weeks, mice (n = 5 per group) were challenged with IAV X31 (103 pfu). (C) IAV titre in lungs was determined by plaque assay at 5 d.p.i. (n = 6).",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "Bone marrow from wild-type (Atg16L1+/+) was used to reconstitute irradiated littermate control mice (B6 WT → control [●] ) or δWD mice (B6 WT → δWD [○] ). Bone marrow from δWD mice was used to reconstitute irradiated δWD mice (δWD → δWD [▲] ). After 12 weeks, mice (n = 5 per group) were challenged with IAV X31 (103 pfu). (D) Lungs taken at 5 d.p.i. were analysed for neutrophils (Ly6G), neutrophil extracellular traps (NET; anti-H3) and macrophages (Iba-1) .",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "δWDphag mice lack non-canonical autophagy in myeloid (LysMcre) cells Offspring negative for LysMcre were used as littermate controls. Mice (n = 6 per group) were challenged intranasally with IAV X31 (103 pfu). (A) Mice were monitored for weight loss at indicated time-points.",
    "ncbi_link": "cre: 
LysM: "
  },
  {
    "caption": "δWDphag mice lack non-canonical autophagy in myeloid (LysMcre) cells Offspring negative for LysMcre were used as littermate controls. Mice (n = 6 per group) were challenged intranasally with IAV X31 (103 pfu). (B) IAV titre in lungs was determined by plaque assay at 5 d.p.i. (n = 6).",
    "ncbi_link": "cre: 
LysM: "
  },
  {
    "caption": "δWDphag mice lack non-canonical autophagy in myeloid (LysMcre) cells Offspring negative for LysMcre were used as littermate controls. Mice (n = 6 per group) were challenged intranasally with IAV X31 (103 pfu). (C) IL-1β mRNA transcripts in lung at 5 d.p.i. were determined by qPCR.",
    "ncbi_link": "cre: 
LysM: 
IL-1β: 16176"
  },
  {
    "caption": "δWDphag mice lack non-canonical autophagy in myeloid (LysMcre) cells Offspring negative for LysMcre were used as littermate controls. Mice (n = 6 per group) were challenged intranasally with IAV X31 (103 pfu). (D) Precision-cut lung slices from control and δWD mice were infected with IAV. Virus titres were determined at indicated time points.",
    "ncbi_link": "cre: 
LysM: "
  },
  {
    "caption": "A). The WD domain of ATG16L1 reduces IAV replication in MEFs. Cells were infected with IAV and virus titres were estimated at 8 hours post infection by plaque assay.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "(I, J) Interferon signalling increases in δWD MEFs. MEFs from δWD or littermate control mice were infected with IAV. At the indicated time points, mRNA transcripts were evaluated by qPCR for IFIT1 (I) and ISG15 (J).",
    "ncbi_link": "IFIT1: 15957
ISG15: 100038882"
  },
  {
    "caption": "C. Western blot (WB) analysis of splicing factors for Vector and 2FLAG-eIF4E U2OS  cell lines. Myc, Mcl1, and cyclin D1  (CCND1) served as positive controls, and β-actin as a loading control. Both 2FLAG-eIF4E  (2Flag-eIF4E) and endogenous eIF4E  (endog-eIF4E) are shown. Each β-actin blot  corresponds to the above western blots. Experiments were carried out at least three independent times, and one representative experiment is shown.",
    "ncbi_link": "FLAG: 
eIF4E: 13684"
  },
  {
    "caption": "D. WB  analysis of splicing factors as a function of eIF4E  reduction using CRISPR-eIF4E  and CRISPR-Ctrl U2OS  cell lines. Myc, Mcl1  and CCND1  served as positive controls, and β-actin a loading control. Each  β-actin blot  corresponds to the  western blots immediately above. Experiments were carried out at least three independent times, and one representative experiment is shown.",
    "ncbi_link": "CRISPR: 
eIF4E: 1977"
  },
  {
    "caption": "A. WB  analysis of the impacts of S53A 2FLAG-eIF4E  (2Flag-S53A) relative to WT 2FLAG-eIF4E  (2Flag-eIF4E) on SF production. CCND1  served as positive controls, and β-actin or HSP90  as loading controls. Both 2FLAG-eIF4E  (2Flag-eIF4E) and endogenous eIF4E  (endog-eIF4E) are shown. Each β-actin or HSP90 blot  corresponds to the above western blots. S53A eIF4E  protein levels are indistinguishable from eIF4E. Experiments were carried out using three separate clones for eIF4E, S53A and Vector controls, and one representative experiment is shown. (Right) Western blots  were quantified by FIJI, intensities normalized to Vector control and plotted using PRISM. The mean, standard deviation, and p-values are shown. Student t-test: * p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "FLAG: 
Flag: 
eIF4E: 13684
eIF4E: 1977"
  },
  {
    "caption": "B. Polysomal  loading analysis was measured to assess the relevance of  eIF4E's capacity to increase translation efficiency on SF protein production. Top panel shows the polysomal  profile (at 254 nm) demonstrating that 2FLAG-eIF4E  overexpression did not alter the profile relative to Vector controls, consistent with previous studies Polysomes  were isolated by size exclusion chromatography (SEC) and thus the heaviest polysomes  elute first and monosomes   last. (Middle and Bottom panels) RNAs were monitored on heavy, light or monosome polysomes  using  RT-qPCR  and presented as a fraction for the given RNA. Known translation targets of eIF4E, MYC  and VEGF  was shifted to higher polysomes  in eIF4E  overexpressing cells as well as SF-encoding RNAs with altered polysomes  (middle) or those that were unchanged by eIF4E  including the negative control ACTB  are in the bottom panel Experiments were carried out in biological duplicates using different clones. Means are shown and p-values calculated using ANOVA (PRISM) . Data information: ANOVA test, * p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "FLAG: 
ACTB: 60
eIF4E: 13684
eIF4E: 1977
MYC: 4609
VEGF: 7422"
  },
  {
    "caption": "B.  Western blot  analysis of untreated (Ctrl) and Ribavirin  treated (Rib) Vector and eIF4E NOMO-1 cell lines. Myc, and Mcl1  served as positive controls, and β-actin as a loading control. Each β-actin blot  corresponds to the above WBs. Experiments were carried out at least three independent times, and one representative experiment is shown. Ribavirin  dose was 10uM which is clinically achievable",
    "ncbi_link": "eIF4E: 13684"
  },
  {
    "caption": "E. Total levels of UsnRNA in NOMO-1 Vector and eIF4E  cells monitored by RT-qPCR. Data were normalized to Vector control and shown as a fold change. The mean and standard deviation, as well as p-values (using Student t-test) were derived from three biological replicates each carried out in triplicate for all panels.",
    "ncbi_link": "eIF4E: 13684"
  },
  {
    "caption": "C. Validation of splicing targets identified by rMATs in U2OS (upper panel) and  NOMO-1 (lower panel) cell lines. RT-qPCR analysis using specific primers for each splicing event normalized to the corresponding total levels of that given transcript Data were normalized to Vector control to calculate fold change. The mean and standard deviation, as well as p-values were derived from three biological replicates. P-values were calculated between eIF4E  overexpressing and Vector cells (when the asterisk is over eIF4E), and eIF4E  cells treated with Ribavirin  vs eIF4E  overexpressing untreated cells (for the asterisk over Ribavirin). Data information: Student t-test, * p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "eIF4E: 13684"
  },
  {
    "caption": "D. eIF4E    associates with both pre-mRNA splicing  substrates and their spliced products. The enrichment of mRNAs for splicing  targets in eIF4E-RIPs  versus input mRNAs from the nuclear  fractions of 2FLAG-eIF4E U2OS  cells monitored by RT-qPCR  using primers for the specific splice event (S for \"spliced\"), pre-mRNA specific primers to the relevant intron or intron-exon boundary (NS for \"unspliced\"), and primers specific to common regions present in all spliced and not-spliced mRNAs (All). Data were normalized to input samples and presented as a fold change. The mean, standard deviation and p-values (Student t-test) were derived from three independent experiments (each carried out in triplicate). Data information: Student t-test, * p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "FLAG: 
eIF4E: 13684"
  },
  {
    "caption": "(A-C) Representative western blots of Pum1, Pum2, Fmrp, Ago2, Rbfox3, Cnot1, and Mov10 in (A) cerebellum, (B) hippocampus, and (C) cortex in both male (left panel) and female (right panel) WT, Pum1+/-, and Pum1-/- mice. All the experiments were conducted with equal numbers of 10-week-old male and female mice per genotype, for a total of at least 6 mice per genotype Graphs below show quantification for each protein by brain region, sex, and genotype. All data were normalized to Gapdh protein levels. P values were calculated by two-tailed Student's t test. *p < 0.05, **p < 0.01, ***p < 0.001. P1 indicates Pum1.",
    "ncbi_link": "Pum1: 80912"
  },
  {
    "caption": "(D) Heatmap showing 166 microRNAs from cerebella of Pum1-/- male and female mice that were dysregulated (fold change -3 to +3) relative to wild-type cerebellum. (E) Heatmap showing mRNA quantification by qPCR for 49 targets co-bound by a minimum of eight dysregulated miRNAs (>25% change) from panel D. Statistical significance and magnitude of dysregulation are illustrated for both male and female",
    "ncbi_link": "Pum1: 80912"
  },
  {
    "caption": "(A, B) IP against PUM1 from Subject 1 (S1, R1147W) (A) and Subject 2 (S2, T1035S) (B) compared to their respective age-, sex-, and cell type- matched healthy controls confirm the interactions between PUM1 (used here as a positive control), and PUM2, FMRP, AGO2, CNOT1, and MOV10. Input (1%) was used as a loading control and IP against IgG was used as a negative control. GAPDH was used here as loading control, see Methods for quantification.",
    "ncbi_link": "PUM1: 9698"
  },
  {
    "caption": "(B) Representative western blots (left panel) and relative quantifications (right panel) of PUM1 and its interactors (AGO2, CNOT1, FMRP, and MOV10) in R1147W patient-derived cell lines after Myc-PUM1-WT expression.",
    "ncbi_link": "Myc: 
PUM1: 9698"
  },
  {
    "caption": "(C) mRNA quantification of the top 15 shared target genes from panel A in R1147W patient-derived cell lines after Myc-PUM1-WT expression.",
    "ncbi_link": "Myc: 
PUM1: 9698"
  },
  {
    "caption": "(A) SARS-CoV-2 genomic view showing the distribution of normalized 22nt small RNA reads from Caco-2 and A549-ACE2 cells at 24 and 48 hpi. The most abundant small RNAs are marked by the red and blue boxes. For all the experiments shown n=2.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(C) Percentage of conservation along the nucleotide positions in the ORF7a among 4,055,609 sequenced SARS-CoV-2 genomes. The first 70 nt are shown in red and shows a higher percentage of conservation compared to the rest of the sequence of ORF7a. Boxplot shows the distribution of conservation percentage for each nucleotide either in the first 70 nt or 71-366 nt of ORF7a among 4,055,609 sequenced SARS-CoV-2 genomes. Box plots display median (line), first and third quartiles (box), and 5th /95th percentile value (whiskers). Each dot represents the outliers. Two-tailed P values were calculated using the student's t-test.",
    "ncbi_link": "ORF7a: 43740573"
  },
  {
    "caption": "(A) Log2 fold changes of the levels of hsa-miR-let-7a, CoV2-miR-O7a.1 and COV2-miR-O7a.2 in DICER1 knockdown SARS-CoV-2-infected A549-ACE2 cells compared to control cells analyzed by stem-loop RT-qPCR. Results from three independent replicates are shown.",
    "ncbi_link": "CoV2-miR-O7a.1: 
COV2-miR-O7a.2: 
ACE2: 59272
DICER1: 23405
hsa-miR-let-7a: 406881"
  },
  {
    "caption": "(B) In vitro kinetics of DICER1 mediated cleavage of pre-CoV2-miR-O7a stem-loop precursor, pre-CoV2-miR-O7a with mutations that prevent the formation of stem-loop structure and pre-hsa-miR21. Folded conformations for the three precursor molecules are shown. Fold change in the production of mature CoV2-miR-O7a.2 is shown in presence of DICER1 compared to control reaction (no DICER1) as measure by stem-loop RT-qPCR. Bars and error bars represent the average and standard deviation from three independent experiments.",
    "ncbi_link": "CoV2-miR-O7a: 
CoV2-miR-O7a.2: 
DICER1: 23405
hsa-miR21: 406991"
  },
  {
    "caption": "(C) Expression levels of the virus-derived miRNAs as a percentage of the viral genome. Absolute quantification of virus-derived miRNAs and viral genome from infected A549-ACE2 cells was performed using two spike-in (see methods). Line represents the average and individual dots represent data from two independent experiments.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(D) copy number per cell of hsa-miR-let-7a, CoV2-miR-O7a.1 and CoV2-miR-O7a.2 in infected A549-ACE2 cells quantified using a synthetic small RNA spike-in standard curve by stem-loop RT-qPCR. Levels of hsa-miR-let-7a were normalized for the percentage of infected cells. Bars and error bars represent the average and standard deviation from at least three independent experiments.",
    "ncbi_link": "CoV2-miR-O7a.1: 
CoV2-miR-O7a.2: 
ACE2: 59272
hsa-miR-let-7a: 406881"
  },
  {
    "caption": "(E) Loading of hsa-miR-let-7a, CoV2-miR-O7a.1 and COV2-miR-O7a.2 into AGOs as measured by stem-loop RT-qPCR and analyzed as a percentage of input from the immunoprecipitates (IPs) of either pan-AGO IP or control IgG IP from infected A549-ACE2 cells. Levels of miRNA were normalized for the percentage of infected cells.",
    "ncbi_link": "CoV2-miR-O7a.1: 
COV2-miR-O7a.2: 
ACE2: 59272
hsa-miR-let-7a: 406881"
  },
  {
    "caption": "(B) Relative firefly luciferase normalized to Renilla luciferase of pmirGLO Dual-Luciferase miRNA Target Expression Vector with either CoV2-miR-O7a.2 target site or CoV2-miR-O7a.2 site with mutations in seed region at 24 h on co-transfection with CoV2-miR-O7a.2 or control miRNA mimics. Activity on transfecting control miRNA mimic was considered 100 %. Bars and error bars represent the average and standard deviation from three independent experiments.",
    "ncbi_link": "Renilla luciferase: 
CoV2-miR-O7a.2: 
firefly luciferase: "
  },
  {
    "caption": "(D) Kinetics of BATF2 and LAMP3 mRNA levels in non-induced and interferon IFN-α-induced (for 8, 16, and 24 h) A549-ACE2 cells transfected with either control or CoV2-miR-O7a.2 mimics. Normalized read abundances in transcript per million (TPM) are shown for two individual experiments (n=2).",
    "ncbi_link": "CoV2-miR-O7a.2: 
ACE2: 59272
BATF2: 116071
LAMP3: 27074"
  },
  {
    "caption": "(E) Genomic view of the human BATF2 gene showing normalized RNA-seq reads from non-induced and IFN-α-induced (for 8 h) A549-ACE2 cells transfected with either control, CoV2-miR-O7a.1 or CoV2-miR-O7a.2 mimics. The complementary site of CoV2-miR-O7a to BATF2 3´UTR is shown.",
    "ncbi_link": "CoV2-miR-O7a: 
CoV2-miR-O7a.1: 
CoV2-miR-O7a.2: 
ACE2: 59272
BATF2: 116071"
  },
  {
    "caption": "(A, B) Volcano plots showing the log2 fold change and corresponding significance levels of ISGs upon 8 hours of IFN-α treatment in A549-ACE2 cells transfected with CoV2-miR-O7a.1 (A) or CoV2-miR-O7a.2 (B) compared to control mimic. Significantly downregulated genes are marked in red, and upregulated genes in blue. The orange horizontal line indicates two-tailed P = 0.05. n=2, dashed lines represent +1 and -1 log2 fold change.",
    "ncbi_link": "CoV2-miR-O7a.1: 
CoV2-miR-O7a.2: 
ACE2: 59272"
  },
  {
    "caption": "(C) Log2 fold change of ISGs at 8, 16, 24 hours of IFN-α treatment and categorized based on CoV2-miR-O7a.2 target sites 8mer, 7mer-m8, 7mer-A1, and no seed as shown in the schematic. The mean and standard error of the mean is shown. Number of ISGs with 8mer site n=8, 7mer-m8 n= 32, 7mer-A1 n=26 and no seed n= 92. The two-tailed p values were calculated using the Mann-Whitney-Wilcoxon test. ISGs were calculated as all the upregulated genes (≥ 3-fold; padj < 0.05) in two replicates of IFN-induced versus non-induced conditions in all time points.",
    "ncbi_link": "CoV2-miR-O7a.2: "
  },
  {
    "caption": "(A) Heat map showing log2 fold change of expression of ISGs in A549-ACE2 cells across 8, 16 and 24 h time points upon IFN-α treatment compared to non-treated controls. The common upregulated genes (≥ 3-fold; padj < 0.05) in IFN-induced versus non-induced conditions at all time points were categorized as ISGs.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A) Expression levels of CoV2-miR-O7a.1, CoV2-miR-O7a.2 and a 22 nt region from the ORF6 of the viral genome that does not produce detectable levels of small RNAs (Control ORF6) analyzed by stem-loop RT-qPCR from nasopharyngeal swabs of patients tested positive for COVID-19 or another seasonal human coronavirus (HCoV). Relative expression to hsa-miR-let-7a is shown. Ct values in parenthesis refer to the Ct value for the detection of viral genome in patient swab samples.",
    "ncbi_link": "CoV2-miR-O7a.1: 
CoV2-miR-O7a.2: 
hsa-miR-let-7a: 406881
ORF6: 43740572"
  },
  {
    "caption": "a, MEFs of RagA+/+, RagAGTP/+ and RagAGTP/GTP genotypes were deprived of amino acids for 1 h and re-stimulated for 10 min. Whole-cell protein lysates were immunoblotted for indicated proteins.",
    "ncbi_link": "RagA: 68441"
  },
  {
    "caption": "b, Total RNA was extracted from RagA+/+ (n = 3), RagAGTP/+ (n = 3) and RagAGTP/GTP (n = 2) MEFs and RagA mRNA expression determined by quantitative PCR (mean ± s.e.m.).",
    "ncbi_link": "RagA: 68441"
  },
  {
    "caption": "c, Weights of RagA+/+ (n = 24), RagAGTP/+ (n = 52) and RagAGTP/GTP (n = 22) mice at birth (data are scatter dots, mean).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "d, Representative photographs of RagA+/+, RagAGTP/+ and RagAGTP/GTP neonates. Scale bar, 1 cm.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "e, Early suppression of mTORC1 signalling after birth was determined by immunoblotting of protein extracts from liver and heart of RagA+/+ (+/+), RagAGTP/+ (G/+) and RagAGTP/GTP (G/G) neonates immediately after Caesarean section (0 h) or after 1 h of fasting (1 h fast).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "f, Liver and heart extracts from RagA+/+, RagAGTP/+ and RagAGTP/GTP neonates fasted for 10 h were analysed by immunoblotting for the indicated proteins.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "a, Glycaemia drop in RagA+/+, RagAGTP/+ and RagAGTP/GTP and recovery in fasted RagA+/+ and RagAGTP/+ but not in RagAGTP/GTP neonates (+/+: n = 5, 18, 4, 5, 9, 8; G/+: n = 10, 26, 10, 13, 26, 21; G/G: n = 7, 20, 9, 10, 16, 11, for 0, 1, 2, 3, 6 and 10 h, respectively; mean ± s.e.m.).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "b, Rapamycin significantly increases glycaemia in RagAGTP/GTP fasted for 6 and 10 h (mean ± s.e.m.). NS, not significant.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "c, Extension of survival by glucose injections in fasted RagAGTP/GTP neonates (untreated: n = 10; glucose: n = 5).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "e, Left: representative electron microscopy images showing abundant glycogen content in RagA+/+ and RagAGTP/GTP hepatocytes before fasting (0 h, upper panels) and more pronounced glycogen depletion after 10 h of fasting (lower panels) in RagAGTP/GTP neonates. Right: quantification of hepatic glycogen content (+/+: n = 5, 3, 4, 4; G/+: n = 11, 7, 14, 15; G/G: n = 6, 4, 4, 6; for 0, 3, 6 and 10 h, respectively; mean ± s.e.m.; AU, arbitrary units).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": ". f, Partial rescue of hepatic glycogen content in RagAGTP/GTP neonates fasted for 10 h and treated with rapamycin (rapa) (mean ± s.e.m.).",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "g, Quantification of neonatal plasma amounts of branched-chain (BCAA) and essential amino acids at birth (left), after 10 h fasting (middle) and after 10 h fasting with rapamycin treatment (right) (n for +/+, G/+ and G/G, respectively: n = 4, 5 and 4 for 0 h; n = 4, 4 and 3 for 10 h; n = 2, 5 and 3 for rapamycin; mean ± s.d.). Values are expressed relative to RagA+/+ amounts at each time point.",
    "ncbi_link": "RagA: 68441"
  },
  {
    "caption": "h, Extension of survival by injection of a combination of gluconeogenic amino acids (a.a.) in fasted RagAGTP/GTP neonates (untreated: n = 10; amino acids: n = 8). *P  0.05; **P  0.01; ns, P > 0.0",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "a, Top: representative micrographs of autophagosomes and autophagolysosomes in hepatocytes from RagA+/+ neonates fasted for 1 h. Typical autophagosome with a double limiting membrane (arrows); autophagosome and several autolysosomes (arrowheads). Scale bars, 5 µm. Bottom: frequency of the two types of organelle (early: autophagosomes; late: autophagolysosomes) detected in cell profiles of hepatocytes and skeletal myocytes from RagA+/+ and RagAGTP/GTPneonates.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "e, Recombinant LC3B-GFP was expressed in RagA+/+ and RagAGTP/GTPMEFs and LC3B localization, in the presence and absence of amino acids, monitored by fluorescence microscopy. LC3B-GFP (green fluorescent protein) clustering, indicative of autophagy, was observed in amino acid-starved RagA+/+ but not RagAGTP/GTPMEFs. Scale bar, 10 µm.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "f, Localization of recombinant TFEB-GFP was determined in MEFs as in e. Nuclear (active) TFEB was observed in RagA+/+ MEFs upon amino-acid withdrawal.",
    "ncbi_link": "RagA: 68441"
  },
  {
    "caption": "a) AMPKa1/a2 double knockout (DKO) and wild-type (WT) MEFs were deprived of glucose for 1 h and re-stimulated for 10 min. Wholecell extracts were immunoblotted for the indicated proteins.",
    "ncbi_link": "AMPKa1: 5562
a2: 108079"
  },
  {
    "caption": "c, RagA+/+ and RagAGTP/GTP immortalized MEFs were deprived of glucose or amino acids and surviving cells quantified in triplicate after 48 h. Cell number is indicated relative to cell number at the start of the treatment; mean ± s.d.; ***P  0.005",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "d, mTOR localization as detected by immunofluorescence. In HEK-293T cells, glucose deprivation causes mTOR to localize to diffuse small puncta throughout the cytoplasm. Re-addition of glucose leads to mTOR shuttling to the lysosomal surface, co-localizing with the lysosomal protein Lamp2. HEK-293T-RagBGTP cells show mTOR localized at the lysosomal surface, regardless of glucose concentrations. Scale bars, 10 μm.",
    "ncbi_link": "RagBGTP: 10325"
  },
  {
    "caption": "f, RagA+/+ and RagAGTP/GTP primary MEFs were cultured for 1 h in media with the glucose and amino-acid concentrations measured in neonates at birth (0 h) or after fasting for 1 h (1 h) and whole-cell protein extracts were analysed by immunoblotting.",
    "ncbi_link": "GTP: 68441
RagA: 68441"
  },
  {
    "caption": "A,B) Real-time qPCR analysis of ANG-2 levels in retina and RPE/choroid complexes of JR5558 and C57Bl/6J (C57) mice. A) Relative expression levels of ANG-2 were significantly increased in the RPE/choroid complexes of JR5558mice in comparison to C57, at 50 and 62 days old (P = 0.022 at D50 and P = 0.042 and at D62). B) By contrast, retina levels of ANG-2 were not significantly different between C57 and JR5558mice, indicating neovascularization is driven locally by ANG-2. SEM is shown as error bar with n = 4 animals per group. *Denotes statistical significance of JR5558mice compared to wild type C57bl6 using unpaired T-test for each time point analyzed separately.",
    "ncbi_link": "ANG-2: 11601"
  },
  {
    "caption": "(C) Western blot detection of p62 and LC3 in H1299 cells cotransfected with the indicated shRNA and the indicated plasmid and cultured in normal medium or after H2O2 (500μM) treatment. CHK2 NTm, a shRNA nontargetable mutant CHK2 rescue plasmid.",
    "ncbi_link": "CHK2: 11200"
  },
  {
    "caption": "(D) Autophagic flux is shown by representative confocal microscopic images of 293 cells stably-expressing GFP-mCherry-LC3 transfected with the indicated shRNA following HBSS starvation and H2O2 (500μM) treatment for 3h. Scale bar, 10 μm.",
    "ncbi_link": "GFP: 
mCherry: 
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) In vitro kinase assays to test the ability of recombinant CHK2 to phosphorylate recombinant GST-Beclin 1-WT, S9093A (AA), S90A and S93A protein. Reactions were analyzed by SDS-PAGE followed by autoradiography. The asterisks in the blot indicate the phosphorylation of Beclin 1 mutants.",
    "ncbi_link": "Beclin 1: "
  },
  {
    "caption": "(B) Immunoprecipitation of Bcl-2 with Flag-Beclin 1 WT, AA mutant and DD mutant in HCT116 cells in normal medium or after H2O2 (500μM) treatment for 1h.",
    "ncbi_link": "Beclin 1: "
  },
  {
    "caption": "(C-D) Autophagy levels were determined in Beclin 1-depleted H1299 cells with reconstituted expression of Beclin 1 WT, AA mutant or DD mutant in normal medium or after H2O2 (500μM) treatment for 3h in the presence (C) or absence (D) of CHK2.",
    "ncbi_link": "Beclin 1: 8678
CHK2: 11200"
  },
  {
    "caption": "(E) Representative electron microscopic image of an autophagosome (arrow, left panel, AP) and an autolysosome (arrow, right panel, AL) in H1299 Beclin 1 WT cells treated with H2O2 (500μM) for 6 hr. Scale bars, 500 nm. Electron microscopic quantification of autophagosomes (AP) and autolysosomes (AL) in H1299 cells with the indicated plasmids cultured for 6 hr in normal or H2O2 (500μM) treatment. All quantitative data are presented as mean ± s.e.m. from 3 independent experiments; *P < 0.001 compared to Beclin 1 WT; #P < 0.001 compared to Beclin 1 WT treated with H2O2; &P < 0.001 compared to Beclin 1 WT treated with H2O2 in the absence of CHK2.",
    "ncbi_link": "Beclin 1: 8678
CHK2: 11200"
  },
  {
    "caption": "H1299 cells transfected with the indicated plasmids in normal medium or after 12h glucose starvation (C) Representative FACS analysis of apoptosis. Results from three independent experiments are presented as a histogram. Data are presented as mean ± s.e.m. from 3 independent experiments; *P < 0.05 compared to Beclin 1 S9093A (AA) treated with H2O2 or hypoxia (Mann-Whitney test).",
    "ncbi_link": "Beclin 1: "
  },
  {
    "caption": "H1299 cells transfected with the indicated plasmids in normal medium or 48h hypoxia stimulation (D). Representative FACS analysis of apoptosis. Results from three independent experiments are presented as a histogram. Data are presented as mean ± s.e.m. from 3 independent experiments; *P < 0.05 compared to Beclin 1 S9093A (AA) treated with H2O2 or hypoxia (Mann-Whitney test).",
    "ncbi_link": "Beclin 1: "
  },
  {
    "caption": "(E) CHK2+/+ and CHK2-/- mice were subjected to MCAO for 1 hr and reperfusion for 12 h. Contralateral (C) and ipsilateral (I) tissues of the mouse brain were coronally sectioned and stained with 2 % TTC.",
    "ncbi_link": "CHK2: 50883"
  },
  {
    "caption": "(G-J) Immunoblots for p62, p-Beclin 1 Ser90, p-Beclin 1 Ser93 and Beclin 1 in the cortical extracts from ischemia and reperfusion-treated CHK2+/+ and CHK2-/- mice. Quantification of p62, p-Beclin 1 Ser90 and p-Beclin 1 Ser93 protein levels (n = 3 mice). Data are presented as mean ± s.e.m.; *P < 0.05, **P < 0.01 (Student's t-test).",
    "ncbi_link": "CHK2: 50883"
  },
  {
    "caption": "(A) Mitochondrial extracts from 143B cells, COX1∆ and COX2∆ mutant cybrids and their respective isogenic controls (CON-1 and CON-2) were analyzed by SDS-PAGE and immunoblotting with the indicated antibodies. The graphs (right) show densitometric quantifications of the signals normalized to CII subunit SDHA. The mean of three independent controls (CON) was set to 100 and all measurements were referenced to that value. The values represent mean ± SD (n=3-8). Mann-Whitney U test was applied for statistical analyses. Variations between controls and mutants: α, p<0.05; β, p<0.01; γ, p<0.001. Specific variations between COX1∆ and COX2∆ mutants: ∗p<0.05; ∗∗p<0.01.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(B) Digitonized mitochondria (digitonin-to-protein ratio of 2:1) were analyzed by BN-PAGE, followed by CI in gel activity (IGA) assays and Coomassie staining. The SC I+III2+IV1 band (b1) was excised from the control (143B) lane and the SC I+III2 bands (b2 to b4) were excised from the COX1∆ and COX2∆ lanes. Their protein compositions were subsequently analyzed by nano-LC/ESI-MS (see also Figure EV2). The relative position of the molecular weight marker is indicated on the left.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(A) Control 143B cells (left panels), COX1∆ cybrids (middle panels), and COX2∆ cybrids (right panels). The right lane highlights structural subunits of CI (yellow), CIII (light green), and CIV (orange brown), and assembly factors (orange). Intensity-based absolute quantification (iBAQ) values were normalized to the sum of all control values. Top lanes indicate gel slice numbers and their relative native masses.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(A) Excerpts of complexome profiling data showing the distribution of CIV subunits and assembly factors HIGD1A, HIGD2A, CMC1 and COA3 in control (143B), COX1∆ and COX2∆ cybrids. The relative abundance and distribution of detected proteins is shown in the lower graphs. The localization of SC I+III2plus in COX2Δ cybrids is highlighted with a red line. The approximate molecular weights of CIV-containing structures are indicated on the top (in kDa).",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(B) 2D-BN/SDS-PAGE analysis from control (143B) and COX2Δ cybrids followed by immunoblotting with the indicated antibodies. I+III2+IV1, SC containing CI, CIII, and CIV; I+III2plus, SC containing CI, CIII and a COX1-submodule; III2+IV, SC containing CIII and CIV; IV2, CIV dimer; IV, CIV monomer. The presence of a COX1-CMC1-COA3-containing subcomplex is indicated.",
    "ncbi_link": "COX2: 4513"
  },
  {
    "caption": "Mitochondrial extracts from control 143B cells (left), COX1∆ cybrids (right), and COX2∆ cybrids (middle) were immunoprecipitated using antibodies against: (A) CIV subunits COX1 and COX5B. (B) CI subunit NDUFB7. Samples were subsequently analyzed by SDS-PAGE and immunoblotting with the indicated antibodies. In, input. IP, immuno-precipitate. FT, flow-through. Ig, unrelated immunoglobulin used as a negative control.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "Mitochondrial extracts from control 143B cells (left), COX1∆ cybrids (right), and COX2∆ cybrids (middle) were immunoprecipitated using antibodies against: (B) CI subunit NDUFB7. Samples were subsequently analyzed by SDS-PAGE and immunoblotting with the indicated antibodies. In, input. IP, immuno-precipitate. FT, flow-through. Ig, unrelated immunoglobulin used as a negative control.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "Mitochondrial extracts from control 143B cells (left), COX1∆ cybrids (right), and COX2∆ cybrids (middle) were immunoprecipitated using antibodies against: (C) CIII subunit CORE2. Samples were subsequently analyzed by SDS-PAGE and immunoblotting with the indicated antibodies. In, input. IP, immuno-precipitate. FT, flow-through. Ig, unrelated immunoglobulin used as a negative control.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(A) Digitonin-solubilized mitochondria from doxycycline-treated 143B cells, COX1∆ and COX2∆ cybrids were analyzed by BN-PAGE followed by CI-IGA assays (upper panels) or immunoblotting (medium and lower panels) with antibodies against CI subunits NDUFA9 and NDUFS1. The identities of MRC complexes and SCs are as in Figure 1.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(A) Digitonized mitochondria from doxycycline-treated 143B cells and COX2∆ cybrids were analyzed by 2D-BN/SDS-PAGE and western blot with the indicated antibodies.",
    "ncbi_link": "COX2: 4513"
  },
  {
    "caption": "(B) Mean incorporation rates of COX subunits into SC I+III2plus from COX2∆ cybrids. Signals from three independent experiments were quantified and normalized by CII. Time-point values are expressed as percentages of the untreated cells (SS) and indicated as mean ± SD. Control (143B) values for subunits COX4, COX5A and COX6C were obtained from (Moreno-Lastres et al., 2012).",
    "ncbi_link": "COX2: 4513"
  },
  {
    "caption": "C-D SDS-PAGE (C) and BN-PAGE (D) analyses from 143B cells and COX2∆ cybrids transiently transfected either with a COX5B-Myc-DDK construct or with the empty vector, followed by immunoblotting with antibodies against COX5B and CII subunit SDHA (loading control). The identities of MRC complexes and SCs are as in Figure 1. The red arrow points to the accumulation of over expressed COX5B bound to SC I+III2 in control cells.",
    "ncbi_link": "DDK: 
Myc: 
COX2: 4513
COX5B: 12859"
  },
  {
    "caption": "Mitochondrial translation products were pulse-labelled in control 143B cells (left panel), COX1∆ (middle panel) and COX2∆ (right panel) cybrids with [35S]-methionine for 30 minutes in the presence of anisomycin to inhibit cytosolic translation. For chase, cells were washed and incubated with fresh culture medium for the indicated time points (T0-T24 hours). Radiolabeled mitochondrial proteins (indicated on the right) were separated by 2D-BN/SDS-PAGE and visualized by autoradiography. A enlarged section of the SCs region at T24 (delimited by a square) shows the co-migration of COX1 with SC I+III2plus (black arrow) in the COX2∆ cybrids relative to the position of canonical SC I+III2 (gray arrow). The identities of MRC complexes and SCs (bottom) are as in Figure 1. Molecular weight markers are indicated on the left.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "(A) Respiratory chain enzyme activities of control (blue), COX1∆ (red) and COX2∆ (green) cybrids. Enzyme activities were measured in three experimental replicates. Data are expressed as the percentages of control cells, and indicated as means ± SD. Mann-Whitney U test was applied for statistical analyses. Variations between controls and mutants: α, p<0.05; γ, p<0.001. Specific variations between COX1∆ and COX2∆ mutants: ∗p<0.05.",
    "ncbi_link": "COX1: 4512
COX2: 4513"
  },
  {
    "caption": "Zoomed confocal image of NPY-pHluorin expressing (green) hippocampal neuron (DIV14) immunostained for ChgB (red) and corresponding fluorescence intensity plot showing overlap between NPY-pHluorin and ChgB. Scale bar: 2 µm.",
    "ncbi_link": "NPY: 
pHluorin: "
  },
  {
    "caption": "Total ChgB puncta per neuron in uninfected (control) and NPY-pHluorin infected neurons (NPY-pH). Student's t-test: n.s. = not significant, p = 0.90. Mean ChgB fluorescence intensity per puncta per neuron in uninfected (control) and NPY-pHluorin infected neurons (NPY-pH). Student's t-test: n.s. = not significant, p = 0.71.",
    "ncbi_link": "NPY: 
pH: 
pHluorin: "
  },
  {
    "caption": "Correlation between ChgB puncta per neuron and total neurite length (mm) for uninfected control (grey) and NPY-pHluorin infected (green) neurons. Linear regression, inset shows goodness of fit (r2) and significance (p-value) per group. Slopes are not significantly different, ANCOVA: p = 0.19.",
    "ncbi_link": "NPY: 
pHluorin: "
  },
  {
    "caption": "Single isolated hippocampal neurons (DIV14) were labeled with NPY-pHluorin. DCV fusion events were quantified per neuron upon different stimulation paradigms. Histogram of DCV fusion events per stimulation per time point. Stimulations include 1 action potential (AP) (grey), 16 bursts of 50 AP at 50 Hz (light-green), superfusion with 60 mM KCl Tyrode solution for 30 s. (dark-green) and superfusion with 5 μM Ionomycin for 30 s. (blue). Inset: Typical ∆F/F0 trace of rise in intracellular calcium (Fluo5-AM) upon different stimulations. Traces are corrected for baseline (first 10 frames) and normalized.",
    "ncbi_link": "NPY: 
pHluorin: "
  },
  {
    "caption": "Single isolated hippocampal neurons (DIV14) were labeled with NPY-pHluorin. DCV fusion events were quantified per neuron upon different stimulation paradigms. Cumulative plot of fusion events per neuron for different stimulations.",
    "ncbi_link": "NPY: 
pHluorin: "
  },
  {
    "caption": "Single isolated hippocampal neurons (DIV14) were labeled with NPY-pHluorin. DCV fusion events were quantified per neuron upon different stimulation paradigms. DCV fusion events per neuron per stimulation. Kruskal-Wallis with Dunn's correction: *p < 0.05, **p < 0.01, ***p < 0.001. 1AP vs. 5 μM Ionomycin, 16x50 AP,50Hz vs. 60 mM KCl and 60 mM KCl vs 5 μM Ionomycin were non-significant, p > 0.05. DCV release probability per neuron per stimulation. Kruskal-Wallis with Dunn's correction: **p < 0.01, ***p < 0.001. 1AP vs. 5 μM Ionomycin, 16x50 AP,50Hz vs. 60 mM KCl and 60 mM KCl vs 5 μM Ionomycin were non-significant, p>0.05.",
    "ncbi_link": "NPY: 
pHluorin: "
  },
  {
    "caption": "DCV release probability per neuron in CaMKII-positive and negative hippocampus neurons (DIV14) upon repetitive electrical stimulation (16x50AP at 50 Hz). Mann-Whitney U test: n.s. = not significant, p = 0.12.",
    "ncbi_link": "CaMKII: "
  },
  {
    "caption": "C. Real-time qRT-PCR analyses of fold changes in transcript levels for each cytokine/chemokine gene in D-THP-1  cells following   Stx2a (10 ng/mL) intoxication for various time-points in the presence or absence of OSMI-1 (10 µM, final). Data are normalized using GAPDH  as a loading control (n = 3, biological replicates). Data information: For graphs error bar represents mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001. The effects of OSMI-1 were compared with those of the vehicle (DMSO) control at each time-point.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "C. Representative  western blot showing changes in OGT expression (top panel), overall O-GlcNAcylation (second panel), or phosphorylation status of each target protein (lower panels) in THP-1 cells treated with  Stx2a   (10 ng/mL) for 9 h in the presence or absence of OGT  knockdown. D. Quantification of the relative band intensities between each of  phosphorylated- and total-protein bands in (C). Data are normalized against β-actin, which was used as a loading control (n = 3 biological replicates). The effects of   Stx2a in siScr controls were compared with those of lysates from cells maintained in the absence of  Stx2a, and OGT knockdown was compared with that of siScr controls in the presence of Stx2a. (n.s. = not significant). Data information: Error bars for bar graphs are presented as mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001.",
    "ncbi_link": "OGT: 8473"
  },
  {
    "caption": "G. Representative western blot  showing changes of overall O-GlcNAcylation (upper panel), phosphorylation status of each target protein (middle panels) or pro-caspase-3 cleavage (lower panel) in  THP-1  cells treated with  Stx2a  (10 ng/mL) for 9 h in the presence or absence of overexpression of  Akt  (wild-type or T305A/T312A). Data information: Error bars for bar graphs are presented as mean ± S.E.M. Statistical analysis was performed using two-tailed Student's t-test. *P < 0.05; **P < 0.01; and ***P < 0.001.",
    "ncbi_link": "Akt: 208///10000///207"
  },
  {
    "caption": "(A) Schematic representation of the SILAC-based quantitative proteomics experiment in B. subtilis. Cells overexpressing active YqgP (BS50, Table EV2) or its catalytically dead mutant YqgP.S288A (BS51), both auxotrophic for lysine, were grown in parallel in \"heavy\" (containing 13C615N2- Lysine isotope) or \"light\" (containing stable 12C614N2- Lysine) M9 minimal medium, respectively. After mixing the cell cultures in the 1:1 ratio (based on OD600), cell suspension was lysed and the fraction enriched for transmembrane proteome was analysed in a GeLC-MS/MS experiment. Using bioinformatic analysis of the MS data, highest-scoring candidate substrates were further evaluated.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(E) Results of MS analyses of affinity co-purification experiments in wild-type B. subtilis control (strain BTM2, Table EV2) and B. subtilis deficient in endogenous YqgP expressing the wild-type YqgP-sfGFP bait (strain BTM84, Table EV2) or the proteolytically inactive YqgP.S288A-sfGFP bait (strain BBM1, Table EV2). Proteins were considered as potential interactors of YqgP if they were identified only in both positive co-purifications with a minimum of 3 weighted spectral counts or enriched at least 5 times in positive bait samples compared to control ones based on weighted spectral counts. The protein highlighted in red was the only overlapping hit between the two proteomics approaches.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(A) Steady-state cleavage profile of endogenous MgtE processed by endogenous and ectopically overexpressed YqgP from the inducible Phyperspank promoter in living B. subtilis (BTM2 and BTM501, respectively, Table EV2), in minimal medium at low magnesium concentration (10 µM). Strain lacking YqgP (ΔyqgP, BTM78, Table EV2) was used as a control. Proteins were detected by immunoblotting with chemiluminescence detection. Data information: In all panels, endogenous full-length MgtE is indicated by a black arrow, and N-terminal cleavage product by red arrows. Endogenous MgtE was visualised by anti-MgtE(2-275) (α-MgtE)",
    "ncbi_link": "yqgP: 938211
YqgP: 938211"
  },
  {
    "caption": "(B) The cleavage is efficiently inhibited by 1 μM STS736, a specific peptidyl ketoamide rhomboid inhibitor Ticha et al., 2017b(). Data information: In all panels, endogenous full-length MgtE is indicated by a black arrow, and N-terminal cleavage product by red arrows. Endogenous MgtE was visualised by anti-MgtE(2-275) (α-MgtE) and ectopic YqgP by anti-YqgP antibodies.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(C) To map the cleavage site region within endogenous MgtE (second lane from the left, from strain BTM501), MgtE-derived reference fragments encoding first 300, 315, 330 amino acids as well as full-length MgtE (black arrow), were in vitro transcribed and translated. Mobility of the N-terminal cleavage product (red arrow) of MgtE on SDS PAGE was compared to the mobilities of the translated reference fragments. Data information: In all panels, endogenous full-length MgtE is indicated by a black arrow, and N-terminal cleavage product by red arrows. Endogenous MgtE was visualised by anti-MgtE(2-275) (α-MgtE) and ectopic YqgP by anti-YqgP antibodies.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(A) Detection and quantification of the cleavage of endogenous MgtE by YqgP in living B. subtilis cells (BS72, Table EV2) depending on the concentrations of magnesium and manganese ions. Cells were cultivated in glucose M9 minimal medium with limiting (0.01 mM) or high (1 mM) concentration of MgSO4, in the presence or absence of 100 μM MnCl2, and analysed by western blotting with near-infrared detection (upper panel). Black arrow denotes full-length MgtE, and red arrow denotes its N-terminal cleavage product formed by YqgP. The corresponding fluorescence signals were quantified by densitometry, and are displayed as relative specific activity, which is substrate conversion normalized to enzyme expression level (lower panel).",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(B) Growth curves of wild-type (BTM843, Table EV2), yqgP deficient (BTM844, Table EV2) and rescue (BTM845, Table EV2) strains of B. subtilis in M9 minimal medium with limiting magnesium (0.01 mM MgSO4), exposed to manganese stress elicited by adding 75 µM MnSO4 in mid-exponential phase (stress-phase denoted by blueish background). All strains further contain a deletion in the putative manganese efflux pump MntP (ΔywlD, Table EV2). Bottom panel shows that manganese is more toxic in the yqgP deficient strain than in the wild type strain, and that reintroduction of YqgP rescues fitness during manganese stress to above-wild-type level. Top panel shows no difference between the strains in the absence of manganese stress. Data are shown as individual datapoints from three independent experiments overlaid with dashed line connecting average values from each time-point, which illustrates the reproducibility of the assay.",
    "ncbi_link": "yqgP: 938211
YqgP: 938211"
  },
  {
    "caption": "(C) Top panel: growth curves of wild-type (BTM843), yqgP deficient (BTM844) and rescue (BTM845) strains of B. subtilis in M9 minimal medium with limiting magnesium (0.01 mM MgSO4), exposed to manganese shock elicited by adding 75 µM MnSO4 in mid-exponential phase. Bottom panel: manganese toxicity is prevented by further adding 5 mM magnesium (MgSO4) in otherwise identical conditions.",
    "ncbi_link": "yqgP: 938211"
  },
  {
    "caption": "(D) Inhibition of YqgP by a rhomboid-specific peptidyl ketoamide inhibitor (STS736, i.e. compound 9 from Ticha et al., 2017b()) abolishes the YqgP induced fitness of B. subtilis under manganese stress, in a dose-dependent manner, both with endogenous YqgP (top panel) and overexpressed YqgP (bottom panel). Media and growth conditions were identical to those used in panel (B).",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(E) Overexpression of heterologous MgtE inhibits growth of yqgP deficient strain (BTM610, Table EV2) in rich LB medium supplemented with 75 μM MnSO4. Cell fitness is improved by overexpression of YqgP (BTM611, Table EV2) or its catalytically dead mutant YqgP.S288A (BTM612, Table EV2). For clarity, for panels C - E, representative experiments of 2-3 independent biological replicates are shown.",
    "ncbi_link": "yqgP: 938211
YqgP: 938211
MgtE: 936439"
  },
  {
    "caption": "(B) Detection (left panel) and quantification (right panel) of steady-state conversion of endogenous MgtE and model chimeric substrate derived from Providencia stuartii TatA Stevenson et al., 2007Ticha et al., 2017aTicha et al., 2017b(, , ) (schemes in the middle) by ectopically expressed YqgP and its N- and C-terminally truncated variants (strains BS184-187, Table EV2) in living B. subtilis grown in rich LB medium. Black arrows indicate full-length substrates and red arrows indicate cleavage products.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(C) Similar analysis of the same strains but grown in minimal M9 medium (with 10 µM MgSO4) supplemented with increasing concentrations of MnCl­­2. Black arrows denote full-length substrate (MgtE), red arrows denote the cleavage products generated by YqgP. (D) Western blots of four independent experiments shown in panel (C) were quantified by near-infrared fluorescence detection, quantified by densitometry and the results are displayed as fold activation of MgtE cleavage at 100 µM MnCl­­2 relative to 1 µM MnCl­­2 activity. Average values and all fours datapoints are plotted for each indicated YqgP variant.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(A) Detection (left panel) and quantification (right panel) of steady-state conversion of endogenous MgtE by YqgP (strain BS72, Table EV2) grown in minimal M9 medium containing 10 μM MgSO4 and 1 μM each of MnCl2, ZnCl2, CoCl2, NiCl2 and CaCl2 (reference conditions) with the additions of 10 µM or 100 μM of a given divalent cation salt solution (MnCl2, ZnCl2, CoCl2, or NiCl2), or 50 µM and 500 μM for CaCl2. Western blots were quantified by near-infrared fluorescence detection (left), quantified by densitometry and displayed as relative specific activity (graph on the right), which is substrate conversion normalized to enzyme expression level. Black arrow denotes full-length substrate (MgtE), and red arrow denotes the N-terminal cleavage product(s) generated by YqgP. All bands originate from the same western blot and identical treatment series.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(C) Cation toxicity assays and their relationship to YqgP activity. Wild type B. subtilis (BTM2, Table EV2), its variant lacking YqgP (ΔyqgP, BTM78, Table EV2), and the rescue strain ectopically expressing YqgP (BTM501, Table EV2) were cultivated in minimal M9 medium containing 10 μM MgSO4 and 1 μM each of MnCl2, ZnCl2, CoCl2, NiCl2 and CaCl2 (i.e. reference conditions), and in mid-exponential phase were stressed by the addition of either 70 µM MnCl2, 500 µM ZnCl2, 25 µM CoSO4 or 400 µM NiCl2 (pale blue area). YqgP activity specifically improved cell fitness during manganese and zinc stress, while it had no effect on growth of cells cultivated in the presence of high cobalt and nickel concentrations. Representative experiments of 2-3 independent replicates are shown.",
    "ncbi_link": "YqgP: 938211
yqgP: 938211"
  },
  {
    "caption": "(E Detection of steady-state conversions of endogenous MgtE by YqgP variants bearing single-point mutations in putative Mn-binding region (BS184; 187; 196-203, Table EV2), cultivated in modified M9 minimal medium supplemented by low (1 μM) or high (100 μM) MnCl2. Black arrow marks full-length MgtE, and red arrow marks its N-terminal cleavage product by YqgP.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "F) quantification of steady-state conversions of endogenous MgtE by YqgP variants bearing single-point mutations in putative Mn-binding region (BS184; 187; 196-203, Table EV2), cultivated in modified M9 minimal medium supplemented by low (1 μM) or high (100 μM) MnCl2.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(A) The proteolytically dead mutant YqgP.S288A behanes as a pseudoprotease and acts as a substrate adaptor of FtsH. Pattern of C-terminally truncated forms of endogenous MgtE formed in vivo in the presence of ectopically expressed active YqgP (strain BS72, Table EV2) or its inactive S288A mutant (BS73, Table EV2) in rich LB medium in the presence or absence of endogenous FtsH. Black arrow denotes the full-length MgtE substrate, and red arrows denote its cleavage products generated by YqgP. While the presence of the faster migrating YqgP-dependent products (full red arrows) do not depend on the presence of FtsH, the slower migrating product formed in the presence of YqgP.S288A (open red arrow) does, indicating that FtsH protease is responsible for the alternative cleavage of MgtE. The same arrow symbolics are valid throughout this figure.",
    "ncbi_link": "FtsH: 51994661
YqgP: 938211"
  },
  {
    "caption": "(B) Mapping of the boundary of the FtsH generated proteolytic product of MgtE. Immunoblot comparing the SDS PAGE mobility of the N-terminal fragment of endogenous MgtE generated by FtsH in the presence of the pseudoprotease version of YqgP (catalytically dead YqgP.S288A, strains BTM78, BTM502, Table EV2) to the mobilities of in vitro translated reference fragments corresponding to MgtE 1-340, -355 and -370 shows that YqgP.S288A acts as an FtsH adaptor, and that FtsH processing of MgtE in the presence of YqgP.S288A stops at around amino acid 355, which is near or at the cytoplasmic end of TMH 3 of MgtE.",
    "ncbi_link": "YqgP: 938211"
  },
  {
    "caption": "(D) In vivo cleavage of endogenous MgtE in the presence of ectopically expressed full-length YqgP.S288A (strain BS73), YqgPΔNTD.S288A (BS185, Table EV2) or YqgPΔCTD.S288A (BS186, Table EV2), in rich LB medium shows that YqgPNTD is necessary for the FtsH-dependent processing of MgtE.",
    "ncbi_link": "FtsH: 51994661
YqgP: 938211"
  },
  {
    "caption": "(E) Analysis of the in vivo kinetics of formation and fate of MgtE cleavage products. B. subtilis strains expressing YqgP or its S288A mutant (strains BTM78; 501 and 502, Table EV2) in the presence or absence of endogenous FtsH protease (strains BTM795, BTM796 and BTM797, Table EV2) were cultured in LB medium and at early exponential phase, after having been expressing YqgP variants for 30 min, were either left grown untreated (as a control with ongoing translation) or treated with 20 μg/mL tetracycline to stop proteosynthesis (translation shut-off). At given time intervals afterwards, all cultures were analysed by α-MgtE western blotting with near infrared detection. Equal cell number (judged by OD600) was loaded into each lane. Black arrow marks full-length MgtE, red full arrows mark YqgP-dependent and red open arrows mark YqgP.S288A-dependent cleavage product of MgtE.",
    "ncbi_link": "FtsH: 51994661
YqgP: 938211"
  },
  {
    "caption": "B) qPCR Validation of lentivirus-mediated shRNA knockdown of FGL2 and CFTR in intestinal organoids. Significance of sample differences was calculated using the one-tailed student t-test (n=2 biological replicates). All values are mean ± s.d. EV = empty vector.",
    "ncbi_link": "CFTR: 1080
FGL2: 10875"
  },
  {
    "caption": "D) Quantification of FIS response in wt-CFTR organoids (ORG-01(HC)) shown in (C) as area under the curve at 60 min. Significance of sample differences was calculated using two-way ANOVA (n=2 biological replicates). All values are mean ± s.d. E) Quantification of FIS response in F508del-CFTR organoids (ORG-BX-002 (dF/dF)) shown in (C) as area under the curve at 60 min. Significance of sample differences was calculated using two-way ANOVA (n=2 biological replicates). All values are mean ± s.d. F",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "A Example of the mapping results. Wild allele frequency in progeny of a cross of the gab1-1 temperature sensitive allele to the YJM975 strain (y-axis) along the yeast genome (x-axis) at the permissive 26°C (blue) and restrictive 34°C (TS allele loss-of-function, cyan). The allele frequency change between the two temperatures is used in mapping. Labels: selected loci in the cross. Blue regions: called suppressor loci. B ",
    "ncbi_link": "gab1: 851181"
  },
  {
    "caption": "E Experimental validation of RPN8 as the causal suppressor of the rpn11-8 TS mutant. Cultures of the indicated strains were diluted to an optical density at 600 nm of 0.1 and a series of ten-fold dilutions was spotted on agar plates and incubated for 2-3 days at 34°C. UWOPS = UWOPS87-2421. See also Figure EV4.",
    "ncbi_link": "rpn11: 850554
RPN8: 854435"
  },
  {
    "caption": "A,B Suppression of nse3-ts4 and nse4-ts4 temperature sensitivity (A) and DNA damage sensitivity (B) by the NSE1 allele of UWOPS87-2421. Cultures of the indicated strains were diluted to an optical density at 600 nm of 0.1 and a series of ten-fold dilutions was spotted on agar plates and incubated for 2-3 days. UW = UWOPS87-2421. The plates shown in (B) were incubated at 30°C. C ",
    "ncbi_link": "NSE1: 850693
nse3: 851882
nse4: 851453"
  },
  {
    "caption": "E Recruitment of Smc6-FLAG by ChIP-qPCR at two known SMC5/6 binding sites (pericentromere of chromosome XIV and CEN3) and one negative control locus (arm of chromosome III) in G2/M arrested strains. Relative enrichment corresponds to the ratio of the signal after immunoprecipitation (FLAG) over beads alone, normalised to the ratio in wild-type cells at CEN3. Error bars: standard error of the mean of three independent experiments. Statistical significance was determined using an unpaired, two-tailed t-test (* = p < 0.05, ** = p < 0.005). E ",
    "ncbi_link": "SMC5: 854123"
  },
  {
    "caption": "(A-F) Representative confocal images of expanded U2OS centrioles treated with siCT (A, D), siSFI1 (B, E) and siPOC5 (C, F) stained for α/β-tubulin (αβTub, magenta) and SFI1 (A-C, green) or Centrin2/3 (D-F, grey). Insets show top views of expanded centrioles at different positions along the centriole (P= proximal, C= central and D= distal). Note that in the absence of SFI1 and Centrin staining at the distal tip, orientation of the centriole was decided based on the larger diameter of the proximal region compared to the distal one, as previously observed in cryo-tomography (Greenan et al, 2020). White arrowheads points to the distal dot of SFI1 and Centrin that disappear in SFI1-depleted (yellow arrowheads) but not in POC5-depleted centrioles. Scale bars: 200 nm and 100 nm (inset). Longitudinal and radial localization of SFI1 and Centrin2/3 in siCT (A, D), siSFI1 (B, E) and siPOC5 (C, F) are presented below the corresponding image. N=25, 40 and 60 centrioles from 3 independent experiments. N=29, 34, 34 centrioles from 3 independent experiments.",
    "ncbi_link": "POC5: 134359
SFI1: 9814"
  },
  {
    "caption": "(K-N) Representative images of expanded U2OS cells expressing GFP alone or GFP+SFI1-RR and treated with siCT or siSFI1. Cells were stained for α/β-tubulin (αβTub, magenta) and SFI1 (K, green) or Centrin2/3 (M, grey). Yellow asterisk indicates the centriole lacking SFI1 and Centrin distal dots. Scale bar: 250 nm. Expression of GFP+SFI1-RR in siSFI1 treated cell rescues the presence of SFI1 and Centrin at the distal tip of the centriole.",
    "ncbi_link": "GFP: 
SFI1: 2541242
SFI1: 9814"
  },
  {
    "caption": "(O, P) Representative confocal images of expanded Cetn2 WT, Cetn KO or Cetn2 rescue RPE-1. Cells were stained for α/β-tubulin (αβTub, magenta) and Centrin2 (O, grey) or SFI1 (P, green). Arrowheads indicate the presence (white) or the absence (yellow) of Centrin2 and SFI1. Scale bar: 200nm. Quantification shows the total absence of Centrin2 in the KO cells correlating with the absence of SFI1. Both Centrin2 and SFI1 localization are rescued when Centrin2 is re-expressed in KO cells.",
    "ncbi_link": "Cetn: 1069
Cetn2: 1069
SFI1: 9814"
  },
  {
    "caption": "(A) Representative confocal images of expanded duplicating centrioles from siCT- and siSFI1- treated U2OS cells. Cells were stained for SFI1 (green) and α/β-tubulin (αβTub, magenta). Inset shows a distal position of the mother centriole where SFI1 signal is visible. White arrowhead indicates the position of SFI1 distal dot in the procentriole of control cell, which is lost in SFI1-depleted cells (yellow arrowhead). Scale bars: 200 nm. (B) Quantification of the percentage of SFI1-negative procentrioles. (C) Quantification of the percentage of duplicating centrioles.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(D) Representative confocal image of expanded duplicating centrioles from siCT and siSFI1 U2OS treated cells. Cells were stained for HsSAS-6 (yellow) and α/β-tubulin (αβTub, magenta). Quantification shows no difference in the percentage of HsSAS-6-positive centrioles in siSFI1-depleted cells compared to control cells. (E) Representative confocal image of expanded duplicating centrioles from siCT and siSFI1 U2OS treated cells. Cells were stained for STIL (yellow) and α/β-tubulin (αβTub, magenta). Quantification shows no difference in the percentage of STIL-positive centrioles in siSFI1 compared to control cells.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(F) Top views of expanded U2OS centrioles treated with siCT or siSFI1 stained for α/β-tubulin (αβTub, magenta). Scale bars: 200 nm. (G) Roundness index of centrioles from siCT and siSFI1-treated cells. (H) Length (circle) and diameter (square) of expanded centrioles in siCT or siSFI1-treated cells.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(I) Representative confocal images of expanded U2OS centrioles from siCT and siSFI1-treated cells stained for α/β-tubulin (αβTub, magenta). White stars point to broken microtubule wall. Scale bars: 200 nm. (J) Percentage of abnormal centrioles in the indicated conditions.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(K) Top views of expanded procentrioles from U2OS cells treated with siCT or siSFI1 and stained for α/β-tubulin (αβTub, magenta). (L) Roundness index of procentrioles from siCT and siSFI1-treated cells.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(M) Representative confocal images of expanded U2OS centrioles from siCT- and siSFI1-treated cells stained for α/β-tubulin (αβTub, magenta) and Centrin (Cetn2/3, grey). White dashed lines delimitate the proximal, central and distal regions. White star points to the broken microtubule wall. (N) Centrin coverage (% of the total tubulin length) along the centriole in the indicated conditions.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(O) Representative images of expanded U2OS expressing GFP alone or GFP+SFI1-RR and treated with siCT or siSFI1. Cells were stained for α/β-tubulin (αβTub, magenta) and SFI1 (green) or Centrin2/3 (grey). Red arrowhead indicates abnormal centriole. (P) Percentage of abnormal centrioles in the indicated conditions.",
    "ncbi_link": "GFP: 
SFI1: 2541242
SFI1: 9814"
  },
  {
    "caption": "(F) Representative widefield images of expanded centrioles during ciliogenesis from siCT and siSFI1 RPE-1 treated cells. Cells were stained for α/β-tubulin (magenta) and SFI1 (green). Yellow asterisks indicate the absence of SFI1 at the distal tip of the centrioles. Red arrowhead indicates abnormal centriole. Scale bar: 250 nm. (G) Percentage of RPE-1 cells with centrioles SFI1-positive (intact SFI1), partially depleted (partial SFI1) or totally missing SFI1 (no SFI1) at the distal dot in siSFI-treated cells. (H) Percentage of abnormal centrioles in RPE-1 cells treated with siSFI1.",
    "ncbi_link": "SFI: 9814
SFI1: 9814"
  },
  {
    "caption": "(I) Representative widefield images of expanded centrioles during ciliogenesis from siCT and siSFI1 RPE-1 treated cells. Cells were stained for α/β-tubulin (magenta) and CP110 (yellow). (J) Percentage of ciliated cells observed in U-ExM under the indicated conditions. (K) Percentage of CP110 capped/uncapped centrioles under the indicated conditions.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(L) Representative widefield images of expanded RPE-1 during ciliogenesis, expressing GFP alone or GFP+SFI1-RR and treated with siCT or siSFI1. Cells were stained for α/β-tubulin (αβTub, magenta) and CP110 (yellow). Arrowheads indicate a cilium. (M) Percentage of ciliated cells observed in U-ExM in the indicated conditions. (N) Percentage of CP110 capped/uncapped centrioles in the indicated conditions.",
    "ncbi_link": "GFP: 
SFI1: 2541242
SFI1: 9814"
  },
  {
    "caption": "(A- D) Representative widefield images of expanded centrioles during ciliogenesis from siCT (A, B) and siSFI1 (C, D) RPE-1 treated cells. Cells were stained for α/β-tubulin (magenta) and CEP164 (red hot). Note the abnormal organization of the distal appendage protein CEP164 in siSFI1-treated cells. (E-H) Representative widefield images of expanded centrioles during ciliogenesis from siCT (E, F) and siSFI1 (G, H) RPE-1 treated cells. Cells were stained for α/β-tubulin (magenta) and CEP90 (cyan). (I) Frequency distribution of the number of dots per centriole formed by CEP164 in indicated conditions. (J) Frequency distribution of the number of dots per centriole formed by CEP90 under the indicated conditions. (K) Percentage of cells presenting abnormal CEP164 and CEP90 under the indicated conditions.",
    "ncbi_link": "SFI1: 9814"
  },
  {
    "caption": "(a) RT-PCR expression and quantification of IGF1, IGF1Rβ and IGF2 levels in untreated C2C12 and shCD20 C2C12 myoblasts and 10 nM IGF1-treated C2C12 and over-expressing CD20 C2C12 myoblasts. Each experiment was replicated independently four times.",
    "ncbi_link": "IGF1: 16000
IGF1Rβ: 16001
IGF2: 16002
CD20: 12482"
  },
  {
    "caption": "Representative CD20 immunoprecipitation using anti-pSer+pThr in (d) sh-empty (shCTR)- and shCD20-treated C2C12 cells treated with anti-Flag and 10 nM anti-IGF2R, as indicated. Densitometric analysis of data are expressed as the ratio of CD20/vinculin or pSer+pThr/CD20 and are shown normalized to vinculin in arbitrary units in the lower panels shown Two-way ANOVA. *p<0.05; **p<0.01; ****p<0.0001. Each experiment was performed in triplicate wells. All values are expressed as the mean ± SEM.",
    "ncbi_link": "CD20: 12482"
  },
  {
    "caption": "(f) Representative WB of IGF2R and phosphorylated IGF2R (pIGF2R) in untreated, shCD20-treated and anti-IGF2R-treated C2C12 cells. Densitometric analysis of data are expressed as the ratio of IGF2R/actin or pIGF2R/IGF2R in arbitrary units in the lower panels. One-way ANOVA. *p<0.05; Each experiment was performed in triplicate wells. All values are expressed as the mean ± SEM.",
    "ncbi_link": "CD20: 12482"
  },
  {
    "caption": "(d) Over-expressing CD20 in C2C12 myoblasts that co-expressed CD20 (in green) and IGF2R (in red). DAPI-labelled nuclei are shown in blue. Scale bars=75 μm.",
    "ncbi_link": "CD20: 931"
  },
  {
    "caption": "(e) Representative CD20 and IGF2R immunoprecipitation products immunoblotted for IGF2R and CD20, respectively, in UNTREATED and shCD20-treated C2C12 cell membranes and whole lysates of proteins. The immunoprecipitation output is shown as IP neg.",
    "ncbi_link": "CD20: 12482"
  },
  {
    "caption": "(f) Myotubes immunofluorescence of cells in proliferation medium (P.M.) and after 2, 4 and 6 days of myogenic differentiation in serum free medium. Control (untreated), shCD20-treated C2C12 cells, C2C12 and HSkM myoblasts pre-treated with anti-IGF2R for 24 hours were stained. Desmin-positive myotubes are shown in green. Scale bars=75 μm.",
    "ncbi_link": "CD20: 12482"
  },
  {
    "caption": "(h) Representative WB of anti-myogenin, anti-Myf5, anti-MyHC and anti-β-actin in total protein lysates obtained from untreated, shCD20-treated C2C12 cells, and C2C12 and HSkM myoblasts pre-treated with anti-IGF2R for 24 hours; cells were collected under P.M. and after 2, 4 and 6 days of myogenic differentiation. Densitometric analysis of WB data expressed as the ratio of the indicated antibody/β-actin in arbitrary units. Two-way ANOVA test. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001 in comparison to the results obtained in untreated cells at the corresponding time point. ##p<0.01; ###p<0.001; ####p<0.0001 in comparison to the results obtained in shCD20-treated C2C12 cells at the corresponding time point. Each experiment was performed in triplicate wells. All values are expressed as the mean±SEM.",
    "ncbi_link": "CD20: 12482"
  },
  {
    "caption": "C-F Mouse kidney was lysed, treated with or without RNase I, and RNA was isolated. The RNA was reverse transcribed with the indicated primers for (C,E) Hifa  and (D,F) Xbp1u  mRNA, and then analyzed by Real Time PCR for disomes using the indicated primers. ∆CT = (∆CT = CT-RNase - CT+RNase). Biological replicates (from three males), with mean ± SD are shown. * P < 0.05, ** P < 0.01, by unpaired two-tailed t-test.",
    "ncbi_link": "Hifa: 13819
Xbp1u: 22433"
  },
  {
    "caption": "(F) WB analysis of p-AMPK, p-ACC, p-Raptor and total AMPK, ACC, Raptor protein in 293T cells transfected with shRNAs targeting LKB1, CaMKK2, TAK1 or a non-targeting control (NTC) that were treated with cystine-deficient medium for 8 h. Actin served as the loading control.",
    "ncbi_link": "CaMKK2: 10645
TAK1: 6885
LKB1: 6794"
  },
  {
    "caption": " (E) WB analysis of p-AMPK, p-ACC, p-Raptor and total AMPK ACC, Raptor protein expression in 293T cells transfected with shRNAs targeting CARS that were further treated with cystine-deficient medium for 8 h. Actin served as the loading control. ",
    "ncbi_link": "CARS: 833"
  },
  {
    "caption": " (J) WB analysis of p-AMPK and total AMPK protein expression in CARS-overexpressing 293T cells and RCC4 cells that were treated with 1 µg/ml STO-609 or DMSO for 8 h. Actin served as the loading control. ",
    "ncbi_link": "CARS: 833"
  },
  {
    "caption": " (D, E) WB analysis of p-AMPK, p-ACC, p-Raptor and total AMPK, ACC, Raptor, AMPKγ2 protein expression in 293T cells transfected with shRNAs targeting AMPKγ2 that were further treated with cystine-deficient medium for 8 h (D) or transfected with Flag-CARS for 48 h (E). Actin served as the loading control. ",
    "ncbi_link": "Flag: 
CARS: 833
AMPKγ2: 51422"
  },
  {
    "caption": "(F) 293T cells were transfected with HA-AMPKγ2 alone or with Flag-CARS for 48 h and then cultured with cystine-deficient medium or complete medium for 8 h. Cell lysates were immunoprecipitated with anti-Flag, and a WB analysis was performed.",
    "ncbi_link": "Flag: 
HA: 
CARS: 833
AMPKγ2: 51422"
  },
  {
    "caption": "(C, D) The crystal violet assay (C) and apoptosis rate assay (D) were performed in 293T cells transfected with shRNAs targeting NTC, CARS, CaMKK2 or AMPKγ2 and further treated with cystine-deficient medium for 24 h with or without 1 mM AICAR. Data are presented as the mean (± SD) of three independent experiments. NS, not significant; *P < 0.05 [two-tailed Student's t-test], compared with the indicated groups.",
    "ncbi_link": "CaMKK2: 10645
CARS: 833
AMPKγ2: 51422"
  },
  {
    "caption": " (F WB analysis of p-AMPK, total AMPK, CARS, AMPKγ2, and CaMKK2 protein expression with 786-O cells transfected with Flag-EV, Flag-CARS, Flag-CaMKK2 or Flag-AMPKγ2 and further treated with cystine-deficient medium for 8 h. Actin served as the loading control. Data are presented as the mean (± SD) of three independent experiments. NS, not significant; *P < 0.05 [two-tailed Student's t-test], compared with the indicated groups. ",
    "ncbi_link": "Flag: 
CaMKK2: 10645
CARS: 833
AMPKγ2: 51422"
  },
  {
    "caption": "H and I Cholesterol levels in p53+/+ and p53-/- HepG2 cells (H) or HCT116 cells (I) were examined. Protein expression was shown by western blotting (bottom panel).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "C mRNA and protein levels of SQLE in different tissues of p53+/+ or p53-/- mice were determined by qRT-PCR and western blot respectively.",
    "ncbi_link": "SQLE: 20775
p53: 22059"
  },
  {
    "caption": "F and G p53+/+ and p53-/- HepG2 cells were cultured for 48 hours in medium containing fetal bovine serum (Serum) or lipoprotein-depleted FBS (LPDS). Protein expression was shown by western blotting (F). mRNA levels of SQLE were examined by qRT-PCR (G). P: premature SREBP2; M: mature SREBP2.",
    "ncbi_link": "SQLE: 6713
p53: 7157"
  },
  {
    "caption": "Protein expression and mRNA levels of p53+/+ and p53-/- HepG2 cells treated with control siRNA or three separated sets of SREBP2 siRNAs for 72 hours as indicated.",
    "ncbi_link": "SREBP2: 6721
p53: 7157"
  },
  {
    "caption": "F Luciferase reporter constructs containing RE1, RE2, RE1mut or RE2mut were transfected into p53-/- HCT116 cells together with control (PRK5-flag vector) or p53 expression vector (PRK5-flag p53) for 48 hours. Renilla vector pRL-CMV was used as a transfection internal control. Relative levels of luciferase are shown. Data represent three independent experiments. Protein expression is shown G Luciferase reporter constructs containing RE1, RE2, RE1mut or RE2mut were transfected into HEK293T cells together with control (PRK5-flag vector) or p53 expression vector (PRK5-flag p53) for 48 hours. Renilla vector pRL-CMV was used as a transfection internal control. Relative levels of luciferase are shown. Protein expression is shown. ",
    "ncbi_link": "flag: 
Luciferase: 
luciferase: 
p53: 7157"
  },
  {
    "caption": "A-C Squalene (A), lanosterol (B) and cholesterol (C) abundance in p53+/+ and p53-/- HepG2 cells transfected with control or SQLE siRNA for 48 hours were determined via ultra-high pressure liquid chromatography coupled to mass spectrometry (UHPLC-MS). Protein levels were analyzed by western blotting with specific antibodies (A bottom panel).",
    "ncbi_link": "SQLE: 6713
p53: 7157"
  },
  {
    "caption": "B SQLE gene expression in HCC and adjacent normal tissue was analyzed in TCGA Liver Hepatocellular Carcinoma (normal [n=50] versus tumors [n=371]). C SQLE gene expression in COAD and adjacent normal tissue was analyzed in TCGA Colon Cancer (normal [n=41] versus tumors [n=286]). ",
    "ncbi_link": "SQLE: 6713"
  },
  {
    "caption": "J - M p53+/+ HCT116 cells (J and K) and p53+/+ HepG2 cells (L and M) were transfected with SQLE siRNA or control siRNA in the presence or absence of exogenous SQLE cDNA for 48 hours. Cholesterol concentration (upper panel) and protein expression (bottom panel) were determined (J and L). Cell proliferation is shown (K and M).",
    "ncbi_link": "SQLE: 6713
p53: 7157"
  },
  {
    "caption": "C Growth of p53+/+ and p53-/- HepG2 cells transfected with and without exogenous SQLE (HA-SQLE) in LPDS medium. Protein expression is assayed after transfection 24 hours.",
    "ncbi_link": "HA: 
SQLE: 6713
p53: 7157"
  },
  {
    "caption": "G and H Cholesterol levels, protein expression (G) and cell growth (H) of SK-HEP-1 cells stably expressing control shRNA or p53 shRNA in LPDS medium in presence or absence of 5μg cholesterol.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "L Percentage of SA-β-gal-positive cells of p53+/+ and p53-/- HepG2 cells expressing SQLE siRNA or control siRNA (upper panel). Protein expression (middle panel) and representative images (lower panel) are shown . Sacle bar, 100 μm.",
    "ncbi_link": "SQLE: 6713
p53: 7157"
  },
  {
    "caption": "p53-/- C57BL/6N male mice (n=7) were injected with a single dose of diethylnitrosamine (DEN) (25mg/kg) at two weeks and then fed with HFD diet at 4 weeks. Oral administration of terbinafine were given at 13 weeks old as indicated. Shown are liver tumor incidence (L) and tumor numbers (M).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "Freezing phenotype (A) of Col-0, atann1, and atann1 AtANN1 (#10) plants. Twelve-day-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA for non-acclimation, −5°C, 30 min; CA for cold acclimation, −8°C, 40 min). Representative pictures are shown in (A).",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "survival rate (B), and ion leakage (C) of Col-0, atann1, and atann1 AtANN1 (#10) plants. Twelve-day-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA for non-acclimation, −5°C, 30 min; CA for cold acclimation, −8°C, 40 min).",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "Expression of CBFs (D) in Col-0, atann1, and atann1 AtANN1 (#10) plants. Twelve-day-old plants grown on MS medium at 22°C were placed at 4°C for 3 h (D) and total RNA was extracted and subjected to qRT-PCR analysis. Relative transcript levels in untreated Col-0 plants were set to 1.",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "Expression of CBFs targets (E) in Col-0, atann1, and atann1 AtANN1 (#10) plants. Twelve-day-old plants grown on MS medium at 22°C were placed at 4°C for 24 h (E), and total RNA was extracted and subjected to qRT-PCR analysis. Relative transcript levels in untreated Col-0 plants were set to 1.",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "A Time-course analysis of cytosolic free calcium concentration ([Ca2+]cyt) dynamics in 10-d-old wild type (Col-0), atann1, and atann1 AtANN1 complementation line (#10) after treatment with ice-cold water or ice-cold water containing 10 mM LaCl3 (arrow shows the time point of treatment). Luminescence was recorded at 1-s intervals. B Quantification of the cold-induced [Ca2+]cyt changes shown in (A). Peak [Ca2+]cyt indicates the highest [Ca2+]cyt after treatment. ",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "E,F Interaction of OST1 and AtANN1 detected by Co-IP assays in Arabidopsis. Twelve-day-old OST1-Myc overexpressing plants grown on MS medium at 22°C were placed at 4°C for 0, 0.5, 2 h, and total proteins were extracted and immunoprecipitated with anti-Myc agarose beads. The wild type (Col-0) treated with 4°C for 2 h was used as control. The OST1-Myc protein was detected with anti-Myc antibody and the AtANN1 protein was detected with anti-AtANN1 antibody. Representative pictures are shown in (E) and relative protein level in (F).",
    "ncbi_link": "Myc: 
OST1: 829541"
  },
  {
    "caption": "Freezing phenotype (A) of Col-0, ost1-3, atann1, and atann1 ost1-3. Twelve-day-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min). Representative pictures are shown in (A).",
    "ncbi_link": "atann1: 840476
ost1: 829541"
  },
  {
    "caption": "survival rate (B) and ion leakage (C) of Col-0, ost1-3, atann1, and atann1 ost1-3. Twelve-day-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min).",
    "ncbi_link": "atann1: 840476
ost1: 829541"
  },
  {
    "caption": "OST1 gene expression D) in Col-0, OST1-Myc, atann1 and OST1-Myc atann1.",
    "ncbi_link": "Myc: 
atann1: 840476
OST1: 829541"
  },
  {
    "caption": "protein levels of OST1 and AtANN1 (E) in Col-0, OST1-Myc, atann1 and OST1-Myc atann1. OST1 and AtANN1 proteins were detected with anti-Myc and anti-AtANN1 antibodies. HSP90 was used as a control.",
    "ncbi_link": "Myc: 
atann1: 840476
OST1: 829541"
  },
  {
    "caption": "Freezing phenotype (F) of Col-0, OST1-Myc, atann1 and OST1-Myc atann1. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, -5°C, 30 min; CA, -8°C, 40 min). Representative pictures are shown in (F).",
    "ncbi_link": "Myc: 
atann1: 840476
OST1: 829541"
  },
  {
    "caption": "survival rate (G), and ion leakage (H) of Col-0, OST1-Myc, atann1 and OST1-Myc atann1. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, -5°C, 30 min; CA, -8°C, 40 min).",
    "ncbi_link": "Myc: 
atann1: 840476
OST1: 829541"
  },
  {
    "caption": "C In-gel kinase assays of OST1 in Col-0 and ost1-3 mutant under cold stress. Twelve-day-old Col-0 and ost1-3 mutant were treated at 4°C for 2 h. Total protein extracts were prepared and separated on a SDS-PAGE gel containing 0.2 mg/mL GST-AtANN1 as a substrate, and incubated with 70 µCi [γ-32P] ATP. Top, autoradiograph; bottom, CBB staining.",
    "ncbi_link": "ost1: 829541"
  },
  {
    "caption": "E OST1 phosphorylates AtANN1 at S289 in vivo in LC/MS analysis. Total proteins were extracted from 12-d-old AtANN1-Myc overexpressing plants treated at 4°C for 0, 10, 30 and 120 min, followed by trypsin digestion. Phosphopeptides were enriched for mass spectrometry analysis. Representative picture for 10 min was shown.",
    "ncbi_link": "Myc: 
AtANN1: 840476"
  },
  {
    "caption": "Freezing phenotype (A) of Col-0, atann1, and atann1 AtANN1S289E (#5) plants. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min). Representative pictures are shown in (A).",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "survival rate (B), and ion leakage (C) of Col-0, atann1, and atann1 AtANN1S289E (#5) plants. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min).",
    "ncbi_link": "atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "Freezing phenotype (D) of Col-0, Atann1, and atann1 AtANN1S289A (#16) plants. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min). Representative pictures are shown in (D).",
    "ncbi_link": "Atann1: 840476
atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "survival rate (E), and ion leakage (F) of Col-0, Atann1, and atann1 AtANN1S289A (#16) plants. 12-d-old plants grown on MS medium at 22°C were exposed to freezing temperatures (NA, −5°C, 30 min; CA, −8°C, 40 min).",
    "ncbi_link": "Atann1: 840476
atann1: 840476
AtANN1: 840476"
  },
  {
    "caption": "A AtANN1 current recordings in Xenopus oocytes. Whole-cell currents were recorded in Xenopus oocytes injected with ddH2O or with AtANN1, OST1, or AtANN1 + OST1 cRNA. Bath solution was described in Materials and Methods. The voltage protocol as well as time and current scale bars for the recordings are shown. B Current-voltage (I-V) relationship of the steady-state whole-cell currents in Xenopus oocytes described in (A). Negative current is influx of cations into the oocytes. ",
    "ncbi_link": "AtANN1: 840476
OST1: 829541"
  },
  {
    "caption": "D AtANN1 current recordings in oocytes. Whole-cell currents were recorded in Xenopus oocytes injected with ddH2O or with AtANN1, AtANN1S289A, OST1, AtANN1 + OST1, and AtANN1S289A + OST1 cRNA. E Current-voltage (I-V) relationship of the steady-state whole-cell currents in Xenopus oocytes described in (D). ",
    "ncbi_link": "AtANN1: 840476
OST1: 829541"
  },
  {
    "caption": "A Time-course analysis of [Ca2+]cyt dynamics between 10-day-old wild type (Col-0) and ost1-3 mutant after treatment with ice-cold water or ice-cold water containing 10 mM LaCl3 (arrow shows the time point of treatment). Luminescence was recorded at 1-s intervals. B Quantification of the cold-induced [Ca2+]cyt changes shown in (A). Peak [Ca2+]cyt indicates the highest [Ca2+]cyt after treatment. ",
    "ncbi_link": "ost1: 829541"
  },
  {
    "caption": "Micrographs of maximum intensity projections of forebrain sections from 3 mo old GLASTCreERT2/eGFP mice  21 days after tamoxifen treatment Double-positive cells are indicated by arrowheads. CTX: cerebral cortex; DIE: diencephalon; HC: hippocampus. Scale bars: 300 µm (A), 20 µm (B), 75 µm (C), 30 µm (D), Histograms showing quantifications (B, n = 6 animals; 5 region of interest (ROI) covering the diencephalon on a total of 3 slides analyzed per animal Data information: data are presented as mean ± SEM. Each data point represents one animal.",
    "ncbi_link": "eGFP: 
Cre: 2777477
ERT2: 26417
GLAST: 20512"
  },
  {
    "caption": "A-E Micrographs of maximum intensity projections (A - D) or single optical section (E) of forebrain sections stained  as indicated for fluorescent proteins in astrocytes labelled in 8 mo (A, B, E) and 3 mo (C, D) GLASTCreERT2/Confetti mice  at 21 dpt. Note that clusters of duplets (D) and triplets (C) labelled in the same color can be found only in the DIE. Also note that astrocyte somata are often very close together, as also observed after live in vivo imaging of dividing astrocytes Somata  of single cells are highlighted in circles. Data information: CTX: cerebral cortex; DIE: diencephalon; HC: hippocampus. Scale bars: 300 µm (A), 100 µm (B), 50 µm (C, D), 20 µm (E).",
    "ncbi_link": "Confetti: 
Cre: 2777477
ERT2: 26417
GLAST: 20512"
  },
  {
    "caption": "B Micrographs of forebrain  sections of 3 mo old GLASTCreERT2/RPL22HA/eGFP 21 dpt mice stained for HA  show maximum intensity projections of HA+ expressing cells with  astroglial morphology. CTX GM: cerebral cortex grey matter; DIE: diencephalon. Scale bars: 100 µm. C Micrographs of forebrain sections of 3 mo old GLASTCreERT2/RPL22HA/eGFP mice 21dpt  stained  for HA and S100β  showing the specificity of the mouse line with HA  detected only in S100β+ astrocytes. DIE: diencephalon. Scale bar: 70 μm. Data information: CTX GM: cerebral cortex grey matter; DIE: diencephalon; n=3 biological replicates, tissue from 3 mice was pooled",
    "ncbi_link": "eGFP: 
HA: 
Cre: 2777477
ERT2: 26417
RPL22: 19934
GLAST: 20512"
  },
  {
    "caption": "C Example of a Smad4/GFP double-positive astrocyte (indicated by arrowhead) in a single optical section of DIE  from 3 mo old GLASTCreERT2/eGFP mice 21 dpt immunostained  as indicated on top of the panel. Orthogonal projections of the area highlighted in left panel of C shown at higher magnification in the right panel. Scale bar: 15 µm.",
    "ncbi_link": "eGFP: 
Cre: 2777477
ERT2: 26417
GLAST: 20512"
  },
  {
    "caption": "D Example of a proliferating  (PCNA+, arrowhead) astrocyte in a single optical section of DIE  from 3 mo old  GLASTCreERT2/eGFP mice  21 dpt immunostained as indicated on top with single channels shown in middle and right panels. Scale bars: 15 µm.",
    "ncbi_link": "eGFP: 
Cre: 2777477
ERT2: 26417
GLAST: 20512"
  },
  {
    "caption": "F, G Histograms depicting percentage of the  neurosphere-generating cells obtained from the DIE (F) or SEZ (G) of GLASTCreERT2/Smad4fl/fl/eGFP or GLASTCreERT2/Smad4WT/WT/eGFP, as indicated on the x-axis (n = 3-4 animals for SEZ, 4 to 8 technical replicates analyzed per animal; 4 animals for DIE, 8 technical replicates analyzed per animal). Data information: data are presented as mean ± SEM. F:  GFP  negative and GFP  positive cells comparing wt/wt vs fl/fl animals, adjusted P-value = 0.0408; G: GFP negative and GFP positive cells comparing wt/wt vs fl/fl animals, ns). Each dot represents one n. * P < 0.05, ** P < 0.01 nonparametric 2way ANOVA followed by Sidak's multiple comparisons test",
    "ncbi_link": "eGFP: 
Cre: 2777477
ERT2: 26417
GLAST: 20512
Smad4: 17128"
  },
  {
    "caption": "H Histogram depicting the number  of secondary neurospheres  generated from 10000 Smad4f/f neurosphere cells at 7 days after infection with MLV-based retrovirus containing either CAG-NLS-Cre or only CAG-GFP (n = 11 cultures / animals, 3 technical replicates per condition analyzed; control vs. Cre, P-value = 0.0149). Note the decrease in  DIE astrocyte proliferation in vivo and in  neurosphere formation upon Smad4  deletion Data information: data are presented as mean ± SEM. Each dot represents one n. * P < 0.05, ** P < 0.01 nonparametric Mann-Whitney test).",
    "ncbi_link": "GFP: 
Cre: 2777477
Smad4: 17128"
  },
  {
    "caption": "A-C) Heads of E18.5 foetuses were serially sectioned in coronal orientation and stained with H&E. Representative images of rostro-occipital level-matched sections from age-matched wild-type (n = 2), Bok-/-Bak-/-Bax-/- triple knockout (TKO; n = 4) and QKO foetuses (n = 4) depicting the forebrain, nasal cavity, and tongue are shown. BP, bony palate; Cx, cerebral cortex; ES, epidural space; In, incisor; LV; lateral ventricle; Ma, mandible; MC, mouth cavity; NC, nasal cavity; NS, nasal septum; St, striatum; SVZ, subventricular zone; To, tongue; WP, whisker follicles. Scale bar = 850 µm (A), 1200 µm (B, C).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bok: 51800"
  },
  {
    "caption": "A-C) Representative H&E-stained coronal serial sections of the eye from E18.5 wild-type (n = 2), Bok-/-Bak-/-Bax-/- triple knockout (n = 3), and Bok-/-Bak-/-Bax-/-Bid-/- quadruple knockout (n = 3) foetuses.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bid: 12122
Bok: 51800"
  },
  {
    "caption": "(A) Estimation of BID protein levels in TKO MEFs. DKO MEFs re-expressing human BAK, TKO MEFs, and two human leukaemia cell lines RS4;11 and MV4;11, were lysed and analysed by Western blot for BID levels, using a rat monoclonal antibody raised against human BID (anti-hBID clone 2D1) that also recognises mouse BID. Also present are samples of the human FL-BID protein added at the equivalent concentrations used in (B) and (C). On the right gel, duplicate samples of DKO and TKO cells and permeabilised DKO and TKO cells (from B and C) showing that endogenous mouse BID is cytosolic in these cells. Data shown are representative of 2 independent experiments.",
    "ncbi_link": "BAK: 578"
  },
  {
    "caption": "(B, C) Partial cytochrome c release by FL-BID from mitochondria of TKO MEFs when combined with BIM BH3 peptide or cBID. DKO MEFs re-expressing human BAK or TKO MEFs were permeabilised, and then the cells incubated with the indicated concentrations of Bim BH3 peptide, cBID or FL-BID, alone or in the indicated combinations, at 30oC for 30 min. Cells were then co-stained for cytochrome c and TOM20 and analysed by flow cytometry. Left hand panels show median fluorescence data from replicate experiments (squares denote experiment 1, circles denote experiment 2). Right hand panels show histograms of cytochrome c staining and TOM20 staining from experiment 2 (treatments are as listed in the left-hand panels).",
    "ncbi_link": "BAK: 578"
  },
  {
    "caption": "B. Detection of netrin-1 expression  in the MMTV/neuT  model by immunoblots (Tumor  1 to 3).",
    "ncbi_link": "neuT: 24337"
  },
  {
    "caption": "E. Biodistribution properties of NP137-NODAGA-111In  in MMTV/neuT mice  at 96 h (3 mice) and measured for all organs. Radioactivity  incorporation was quantified by the percentage of the injected dose per gram of organ. Error bars indicate s.d.",
    "ncbi_link": "neuT: 24337"
  },
  {
    "caption": "F. NP137-177Lu  enhances MMTV/neuT mouse survival. Mice  were treated at 3.5 months with PBS, DOTA-NP137  or NP137-177Lu. Kaplan-Meier survival curves  of mice  treated or not with NP137  and considered as dead when cumulative tumors volume reached 2,000 mm3. Mantel Cox test; n = 10 animals/group for PBS; n = 14 animals/group for DOTA-NP137; n = 8 animals/group for NP137-177Lu; p < 0.001 between PBS  and NP137-177Lu  and between DOTA-NP137  and NP137-177Lu.",
    "ncbi_link": "neuT: 24337"
  },
  {
    "caption": "(A-C) qPCR  and western blot analysis indicated an upregulation of hepatic ZBTB22  in diabetic db/db mice, obese ob/ob mice  and high-fat diet  for 12 weeks mice  (n=6 mice). Data information: Data are means ± SEM. **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D) qPCR  and western blot analysis showed an increase of hepatic ZBTB22  in normal C57 mice  after overnight fasting, and a recovery of ZBTB22  expression after refeeding  (n=6 mice). Data information: Data are means ± SEM. **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(E) qPCR  and immunofluorescence  analysis displayed an enhanced expression of ZBTB22  in MPHs  after FSK  treatment for 24h and a reduction of ZBTB22  in MPHs  after insulin  treatment for 15min (n=4 biological replicates), scale bars represent 10 μm. Data information: Data are means ± SEM. **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(A-B) qPCR  analysis the change of genes involved in gluconeogenesis, lipogenesis and fatty acid oxidation in primary hepatocytes  after ZBTB22  overexpression (n=4 biological replicates). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D-E) ZBTB22  overexpression increase lipid  deposition in primary hepatocytes, as shown by the enhanced lipid TOX probes and TG  content (n=4 biological replicates), scale bars represent 10 μm. Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(F-G) qPCR  analysis the change of genes involved in gluconeogenesis, lipogenesis, and fatty acid oxidation in primary hepatocytes  after ZBTB22  knockdown (n=4 biological replicates). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(I-J) ZBTB22  knockdown suppress lipid  deposition in  primary hepatocytes, as shown by the weakened lipid TOX probes and TG  content (n=4 biological replicates), scale bars represent 10 μm. Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(K) qPCR  analysis of mRNA levels of Pgc1α, PCK1  in  primary hepatocytes infected with Ad-shCtrl or Ad-shZBTB22 with or without forskolin  treatment (n=4 biological replicates). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "PCK1: 18534
Pgc1α: 19017
ZBTB22: 81630"
  },
  {
    "caption": "ZBTB22  deletion effectively decrease the  fat mass  of mice  fed on HFD (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D) ZBTB22  deletion enhanced the expression  of genes involved in thermogenesis and fatty acid oxidation in brown adipose tissue from mice  fed on HFD (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(E) ZBTB22  deletion increased the  heat production, CO2  generation and O2  consumption in mice  fed on HFD (n=3 mice).",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "ZBTB22  deletion effectively decrease the fasting blood glucose  of mice  fed on HFD (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D) ZBTB22  deletion significantly changed hepatic expression  of genes involved in gluconeogenesis, lipogenesis and fatty acid oxidation in mice  fed on HFD (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(E) ZBTB22  deletion significantly improved the phosphorylation of AKT  and GSK3β  in the liver  of mice  fed on HFD.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(I) Hepatic ZBTB22   overexpression induces glucose   intolerance  and  insulin  resistance in ZBTB22  deficiency mice  fed on HFD (n=6 mice).",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(J) Hepatic ZBTB22  overexpression decreased the insulin-induced phosphorylation  of AKT  and GSK3β  in the liver  of ZBTB22  deficiency mice  fed on HFD.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(K) qPCR  analysis of hepatic  genes involved in gluconeogenesis, lipogenesis and fatty acid oxidation in ZBTB22  deficiency mice  fed on HFD (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(A-B) Hepatic ZBTB22  silencing decreases the expression  of gene involved in gluconeogenesis, lipogenesis, and fatty acid oxidation in db/db mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D) Hepatic ZBTB22  silencing improved the  glucose  tolerance,  insulin  sensitivity  and pyruvate  tolerance in db/db mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(J-K) Hepatic ZBTB22  silencing decreases serum  inflammatory cytokines levels and hepatic  inflammatory genes expression (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "Hepatic ZBTB22   overexpression increases the expression  of genes involved in gluconeogenesis in normal C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(C) Hepatic ZBTB22  overexpression significantly induced glucose intolerance and   insulin resistance in normal C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "(D) Hepatic ZBTB22  overexpression significantly decreased insulin-induced phosphorylation  of hepatic AKT  and GSK3β  in normal C57 mice.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "Hepatic ZBTB22  overexpression increase serum  inflammatory cytokines levels Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "Hepatic ZBTB22  overexpression increase hepatic expression  of inflammatory genes (n=6 mice). Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "Western Blot analysis showed that ZBTB22-mediated induced the up-regulated expression of PEPCK1  in Ad-ZBTB22  infected mice primary hepatocytes  and livers  (C)",
    "ncbi_link": "ZBTB22: 81630"
  },
  {
    "caption": "Chip  and Chip-qPCR  displayed increase occupancy of ZBTB22  on the promoter region of PCK1  (n=3 biological replicates).",
    "ncbi_link": "PCK1: 18534"
  },
  {
    "caption": "PCK1  silencing , as well as the stimulatory effects of ZBTB22  on SREBP1C expression  (J) (n=4 biological replicates) and cellular glucose  output (K) (n=4 biological replicates) Data information: Data are means ± SEM. *p< 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "PCK1: 18534
SREBP1C: 20787
ZBTB22: 81630"
  },
  {
    "caption": "Hepatic ZBTB22  overexpression failed to change  glucose tolerance,  insulin sensitivity  in PCK1-silencing C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p < 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "PCK1: 18534
ZBTB22: 81630"
  },
  {
    "caption": "(G) Hepatic ZBTB22  overexpression failed to change serum  and hepatic TG  and TC  levels in PCK1-silencing C57 mice  (n=6 mice). Data information: Data are means ± SEM. *p < 0.05, **p< 0.01, ***p< 0.001 by Student's t test.",
    "ncbi_link": "PCK1: 18534
ZBTB22: 81630"
  },
  {
    "caption": "(b, c) Stable FoxO1 knockdown HCT116 cells, or cells with an empty RNAi plasmid, were incubated in a serum-free medium for up to 36 h (b) or treated with 0.5 mM H2O2 for up to 12 h (c); western blotting was performed to detect changes in FoxO1, p62, LC3-II or β-actin.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(e) Autophagic vesicles or autophagosomes in HCT116 cells or stable FoxO1-RNAi HCT116 cells, were observed by electron microscopy after 24 h of serum starvation. The bottom picture enlargement showing clearer autophagic vesicles indicated by an arrow. The graph shows a statistical analysis of autophagic vesicles in HCT116 cells with or without knockdown of FoxO1 in response to serum starvation. Data in e are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(f) LC3-immunopositive punctate signals were observed in HCT116 or in stable FoxO1-RNAi HCT116 cells in response to serum starvation for 24 h or 0.5 mM H2O2 treatment. (g) Quantification of LC3-positive punctate cells in f. Data in g are means ± s. d. (n = 3).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(h) A rescue experiment using a specific mutated FoxO1 plasmid to validate the activity of FoxO1 in the induction of autophagy in HCT116 cells in the presence or absence of serum, with or without E64 and pepstatin A.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(a) A Flag-tagged FoxO1(WT), FoxO1(ΔDB), FoxO1(ΔDB3A) or an empty plasmid was individually transfected into GFP-LC3 pre-transfected H1299 cells, and the cellular localization of FoxO1 (upper panels) or GFP-LC3 punctate signals (lower panels) was observed with a confocal microscope. Scale bars, 10 μm. (b) The numbers of punctate GFP-LC3 cells are represented by the ratio of GFP-LC3-labelled punctate cells to overall survived H1299 cells (at least 200 cells were counted). Data in b are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308
LC3: 440738///81631///84557"
  },
  {
    "caption": "(d) H1299 cells were labelled with [3H]leucine for 48 h, then transfected with a control plasmid or various Flag-FoxO1 plasmids, in the presence or absence of 3-MA or E64 and pepstatin A. Degradation of long-lived proteins was measured at the indicated time, 24 h after transfection. Data in d are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(e) A GFP-tagged FoxO1(3A) or an empty plasmid was co-transfected with a FoxO1-promoter luciferase plasmid into H1299 cells. After 24 h, luciferase reporter activity of FoxO1 was measured. RLU, relative luciferase units. Data are means ± s.d. (n = 3).",
    "ncbi_link": "luciferase: 
FoxO1: 2308"
  },
  {
    "caption": "(f) A set of RNAi-resistant rescue forms of FoxO1 plasmids were transfected into stable FoxO1-RNAi HCT116 cells in the presence or absence of E64 and pepstatin A. Western blotting was performed to detect p62 degradation and LC3-II accumulation.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(g) Flag-tagged FoxO1(WT)r, FoxO1(3A)r, FoxO1(3A-NLSm)r, FoxO1(NESm)r or an empty plasmid were individually transfected into GFP-LC3 pre-transfected HCT116 cells (FoxO1-RNAi treated), and the cellular localization of FoxO1 (upper panels) or GFP-LC3 punctate signals (lower panels) were observed with a confocal microscope. (h) The numbers of punctate GFP-LC3 cells are represented by the ratio of GFP-LC3-labelled punctate cells to overall survived HCT116 cells. Data in h are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) Different FoxO1-expressing plasmids, namely FoxO1(WT), FoxO1(3A), FoxO1(ΔDB), FoxO1(ΔDB3A), FoxO1(NESm) and FoxO1(3A-NLSm), were transfected into H1299 cells and cell fractionation was performed to analyse cellular localization (N, nucleus; C, cytoplasm) of these FoxO1 mutants. PCAF is a loading control for nuclear protein, and actin is the loading control for cytoplasmic protein.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(b) Quantitative PCR was performed to measure the transactivity of autophagy-related genes in transfected H1299 cells with different FoxO1-expressing plasmids (upper panel) or in stable FoxO1-RNAi or non-RNAi-treated HCT116 cells in response to serum starvation for 24 h or 0.5 mM H2O2 for 12 h (lower panel). All data are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(c) Different FoxO1-mutant-expressing plasmids were transfected into H1299 cells and a ChIP assay was performed to measure the binding activity of these mutated FoxO1 to the p27 promoter.",
    "ncbi_link": "p27: 1027
FoxO1: 2308"
  },
  {
    "caption": "(b) HCT116 cells were serum-starved for 24 h and the cytosolic proteins were extracted for co-immunoprecipitation with anti-FoxO1 or anti-SIRT2, followed by probing with anti-SIRT2 or anti-FoxO1, respectively (top and middle panels). FoxO1(WT) was also transfected into H1299 cells and the cytosolic protein was extracted, followed by co-immunoprecipitation with anti-FoxO1 and probing with anti-SIRT2 (bottom panels).",
    "ncbi_link": "FoxO1: 2308
SIRT2: 22933"
  },
  {
    "caption": "(c) HCT116 cells were transfected with SIRT2 RNAi plasmid or an empty control plasmid. At 48 h after transfection, the cytosolic lysate was extracted for probing with SIRT2 or FoxO1 (upper panels), or for co-immunoprecipitation with anti-FoxO1, followed by probing with anti-acetylated lysine (lower panels). IB, immunoblot.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(a, b) H1299 cells were transfected with an empty control plasmid or with the Flag-FoxO1(WT) plasmid. At 24 h after transfection, the cytosolic lysate was extracted for co-immunoprecipitation with anti-FoxO1, followed by probing with anti-mTOR, Beclin 1, Vps34 or Atg1 (a) and with Atg3, Atg4, Atg10, Atg7 or LC3 (b).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(c) H1299 cells were co-transfected with Myc-Atg7, with Flag-FoxO1(WT) or with an empty control plasmid. At 24 h after transfection, the cytosolic lysate was extracted for Flag with anti-Flag, followed by probing with anti-Myc.",
    "ncbi_link": "Atg7: 10533
FoxO1: 2308"
  },
  {
    "caption": "(e) Different Myc-tagged FoxO1 fragments and Flag-tagged Atg7 were co-transfected into H1299 cells, and the cytosolic lysate was extracted for co-immunoprecipitation with anti-Myc, followed by probing with anti-Flag.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(f) HCT116 cells were transfected with an empty control plasmid, an SIRT2(WT)-expressing plasmid or an SIRT2(168A)-expressing plasmid. At 24 h after transfection, cells were serum-starved for 24 h, and the cytosolic lysate was extracted for co-immunoprecipitation with anti-FoxO1, followed by probing with anti-Atg7.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(a) HCT116 cells or stable FoxO1-RNAi HCT116 cells were treated with a non-specific RNAi control or SIRT2-RNAi, and LC3-II accumulation or p62 degradation was detected in the presence or absence of E64 and pepstatin A.",
    "ncbi_link": "FoxO1: 2308
SIRT2: 22933"
  },
  {
    "caption": "(b) HCT116 cells or stable FoxO1-RNAi HCT116 cells were treated with 10 μM AGK2 for 24 h, in the presence or absence of E64 and pepstatin A. Changes in FoxO1, p62 and LC3-II were determined by western blotting (upper panels), or the formation of LC3 punctate signals was observed (lower panels). HCT116 cells were treated with 10 μM AGK2 for 24 h and the formation of LC3 punctate signals was observed. Quantification of the ratio of LC3 punctate cells to overall HCT116 cells is shown in the lower right panel. Data are means ± s.d. (n = 3).",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(c) H1299 cells were transfected with Flag-FoxO1(WT), SIRT2(WT) or SIRT2(168A). At 24 h after transfection, the cell lysate was extracted and immunoblotted with anti-Flag, anti-SIRT2, anti-LC3, anti-p62 or anti-β-actin..",
    "ncbi_link": "FoxO1: 2308
SIRT2: 22933"
  },
  {
    "caption": "(d) HCT116 cells were transfected with a control plasmid, a SIRT2(WT)-expressing plasmid or a SIRT2(168A)-expressing plasmid. At 24 h after transfection, the cells were subjected to serum starvation for 24 h. The cell lysate was extracted and immunoblotted with anti-SIRT2, anti-LC3, anti-p62 or anti-β-actin.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(e) H1299 cells were transfected with Myc-Atg7, Flag-FoxO1(WT) or mutated Flag-FoxO1(KR). At 24 h after transfection, the cytosolic lysate was extracted for co-immunoprecipitation with anti-Myc, followed by probing with anti-Flag.",
    "ncbi_link": "Atg7: 10533
FoxO1: 2308"
  },
  {
    "caption": "(f) H1299 cells were transfected with a control plasmid, Flag-FoxO1(WT), Flag-FoxO1(K262R), Flag-FoxO1(K265R), Flag-FoxO1(K274R) or Flag-FoxO1(KR). At 24h after transfection in the presence or absence of E64 and pepstatin A and immunoblotted, the cell lysate was extracted and immunoblotted with anti-Flag, anti-LC3, anti-p62 or anti-β-actin.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(g) Left: H1299 cells were co-transfected with GFP-LC3, Flag-FoxO1(WT) or Flag-FoxO1(KR). The formation of GFP-LC3-labelled punctate signals was observed 24 h after transfection. Right: quantification of the ratio of GFP-LC3-labelled punctate cells to overall survived H1299 cells. Data in g are means ± s.d. (n = 3). Scale bars, 25 μm (b), 10 μm (g).",
    "ncbi_link": "FoxO1: 2308
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) H1299 cells were transfected with a control plasmid, Flag-FoxO1(WT), Flag-FoxO1(3A), Flag-FoxO1(ΔDB) or Flag-FoxO1(ΔDB3A), in the presence or absence of 10 mM 3-MA (upper panel) or in the presence or absence of 50 μM Z-VAD-fmk (lower panel); cells were stained with propidium iodide (PI) 48 h after transfection. PI-stained (dead) cells were counted by flow cytometry and the percentage cell loss was calculated.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(b) FoxO1(WT) or Flag-FoxO1(ΔDB) was transfected into H1299 cells; 48 h later the autophagic vesicles were observed under an electron microscope. Enlarged images (right) show clearer autophagic vesicles indicated by arrows. Scale bars, 2 μm.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(c) 48 h cells with or without Atg5 RNAi were transfected with FoxO1(WT), and cell death was determined by staining with PI at 48 h after transfection. Data in c are means ± s.d. (n = 3).",
    "ncbi_link": "Atg5: 9474
FoxO1: 2308"
  },
  {
    "caption": "(d) The stable Atg5 knockdown H1299 cells was further transfected with a control plasmid, Flag-FoxO1(WT), or Flag-FoxO1(ΔDB), and the percentage cell loss was quantified by flow cytometry at 48 h after transfection. Data in d are means ± s.d. (n = 3).",
    "ncbi_link": "Atg5: 9474
FoxO1: 2308"
  },
  {
    "caption": "(a) Stable H1299 cells with or without Atg7 knockdown were transfected with a control plasmid (group 1), Flag-FoxO1(ΔDB) (group 2) or Flag-FoxO1(ΔDB-3A) (group 3); 107 cells were then injected into 18 nude mice, with 6 mice per group. Seven weeks later the mice were killed and the tumours were weighed and analysed (bottom graph). Group 1: tumour weights were 1.22 ± 0.78 g (without Atg7 RNAi) and 1.31 ± 0.43 g (with Atg7 RNAi), P = 0.426. Group 2: tumour weights were 0.49 ± 0.18 g (without Atg7 RNAi) and 0.80 ± 0.20 g (with Atg7 RNAi), P = 0.017. Group 3: tumour weights were 1.00 ± 0.40 g (without Atg7 RNAi) and 1.10 ± 0.36 g (with Atg7 RNAi), P = 0.500. Data are means ± s.d. (n = 6).",
    "ncbi_link": "Atg7: 10533
FoxO1: 2308"
  },
  {
    "caption": "(c) HCT116 cells (107) or stable FoxO1-knockdown HCT116 cells (107) were injected into the left or right hind legs of three nude mice. Six weeks later the mice were killed and the tumours were weighed and analysed (bottom graph). Tumour weights were 0.08 ± 0.10 g (without FoxO1 RNAi) and 0.48 ± 0.06 g (with FoxO1 RNAi), P = 0.020. Data are means ± sd. n = 3.",
    "ncbi_link": "FoxO1: 2308"
  },
  {
    "caption": "(A) Gross morphology of control (Ctrl), Sas-4−/−, Sas-4−/− 53bp1−/−, and Sas-4−/− Usp28−/− embryos at E9.5. At least five embryos were considered per genotype and all the double mutant embryos exhibited the rescue criteria mentioned in the text. Scale bar = 500 μm.",
    "ncbi_link": "Sas-4: 219103
53bp1: 27223
Usp28: 57646"
  },
  {
    "caption": "(B, C) Immunostaining for p53 (B) and Cleaved-Caspase3 (Cl-CASP3, C) on transverse sections of Ctrl, Sas-4−/−, Sas-4−/− 53bp1−/−, and Sas-4−/− Usp28−/− embryos at E9.5. The area shown encompasses the ventral neural tube and surrounding mesenchyme. Asterisks in (B) denote non-specific staining of blood cells. Scale bar = 50 μm. (D, E) Quantifications of the p53 (D) and Cl-CASP3 (E) fluorescence signals shown in (B) and (C), respectively. Three embryos per genotype were used for the quantifications. *** p < 0.001, *p<0.05 (two-tailed student's T-test, one-way ANOVA with Tukey's multiple comparisons tests gave similar results). Bars represent mean ± s.d. (D) Ctrl: 1.00 ± 0.06 (n=1770 cells); Sas-4−/−: 6.84 ± 0.34 (n=275), Sas-4−/− 53bp1−/−: 1.85 ± 0.75 (n=690), Sas-4−/− Usp28−/−: 1.50 ± 0.48 (n=975). (E) Ctrl: 1.00 ± 0.70 (n=1690); Sas-4−/−: 7.88 ± 2.62 (n=175); Sas-4−/− 53bp1−/−: 1.43 ± 0.71 (n=1030); Sas-4−/− Usp28−/−: 1.57 ± 0.44 (n=950). ",
    "ncbi_link": "Sas-4: 219103
53bp1: 27223
Usp28: 235323"
  },
  {
    "caption": "(A, B) Whole-mount immunostaining and quantification for p53 on Ctrl and Sas-4−/− embryos at E7.5 (A) and E6.5 (B). Representative sagittal planes are shown and the dotted lines demarcate the epiblast. Quantification of nuclear p53 fluorescence intensity in the epiblast is shown below, normalized to control embryos in the same batch at E7.5 (4 embryos) and at E6.5 (9 embryos). *** p < 0.001 (two-tailed student's T-test). Bars represent mean ± s.d. Scale bars = 100 μm. (A) Ctrl: 1.04 ± 0.00 (n=495 cells); Sas-4-/-: 1.65 ± 0.19 (n=850). (B) Ctrl: 1.00 ± 0.18 (n=1665); Sas-4-/-: 1.16 ± 0.44 (n=1330)",
    "ncbi_link": "Sas-4: 219103"
  },
  {
    "caption": "(A) Immunostaining for the centrosome marker γ-tubulin (TUBG) on Ctrl and Sas-4−/− primary mESCs. The bottom panels are magnifications of the areas marked in the top panels. Scale bars = 20 μm (top) and 10 μm (bottom).",
    "ncbi_link": "Sas-4: 219103"
  },
  {
    "caption": "(B) Immunostaining and quantification for p53 on Ctrl and Sas-4−/− primary mESCs in pluripotent and partially differentiated (diff.) conditions. The quantification of p53 fluorescence intensities was normalized to Ctrl (Four independent experiments). ** p < 0.01, * p < 0.05 (two-tailed student's T-test, the comparison of the genotypes in the "Pluripotent" condition was not significant using the one-way ANOVA with Tukey's multiple comparisons tests). Bars represent mean ± s.d. Scale bar = 50 μm. Pluripotent Ctrl: 1.00 ± 0.02 (n=2030 cells); pluripotent Sas-4-/-: 1.17 ± 0.10 (n=2170); partially diff. Ctrl: 0.62 ± 0.13 (n=2745); partially diff. Sas-4-/-: 1.12 ± 0.24 (n=2000).",
    "ncbi_link": "Sas-4: 219103"
  },
  {
    "caption": "(C, D) Three-day growth curves of WT and Sas-4−/− (C) or p53−/− and Sas-4−/− p53−/− (D) primary mESCs in the indicated conditions starting with 105 cells on Day 0 (Four independent experiments). ** p < 0.01, * p < 0.05 (two-tailed student's T-test). Bars represent mean ± s.d. For details of the measurements, see Materials and Methods (Tables 3 and 4).",
    "ncbi_link": "Sas-4: 219103
p53: 22059"
  },
  {
    "caption": "(E) Northern blot  analysis of circBtnl1  in different tissues of two-month-old mice, 18S RNA  served as a loading control.",
    "ncbi_link": "18S RNA: 
Btnl1: 100038862"
  },
  {
    "caption": "(F， G)  RNA fluorescence in situ hybridization   of circBtnl1 in small intestine tissues (F) and organoid (G). Green region shows the distribution of circBtnl1  using antisense probe, gray region shows the nuclei staining  by DAPI. For (F)，scale bars，5um; for (G)，scale bars，20 um.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(C) Representative images of Ki67 staining  of in  small intestinal  tissues from circBtnl1+/+ and circBtnl1-/- mice. For all representative images, at least three independent experiments were performed with similar results. For every microscope field, average Ki67+ ISC  numbers per crypt  are shown as means ± SD. **P < 0.01 by two-tailed Student's t-test in right panel. Scale bar, 50 μm.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(G) Confocal microscopy  of ISCs  makers Olmf4  in organoids from circBtnl1+/+ and circBtnl1-/- mice. Scale bars, 30 μm. Three independent experiments were performed with similar results, and representative experiments are shown. For every microscope field, average Olmf4+ ISC  numbers per crypt  are shown as means ± SD. **P < 0.01 by two-tailed Student's t-test in right panel in right panel.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(B, C) CircBtnl1 was co-localized with Ddx3y  protein in small intestine tissue (B) and organoid  (C) by RNA FISH, followed by immunofluorescence staining. Scale bars, 5 μm.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(G)  Electrophoretic mobility shift assay (EMSA) using biotin-labeled circBtnl1 and recombinant Ddx3y.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(H) Truncated fragments of biotinylated circBtnl1  were incubated with small intestine crypts lysates, followed by RNA pulldown assay  and  Western blot.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(B)  Small intestine crypt  cells were isolated from circBtnl1+/+ and circBtnl1-/- two-month-old mice, followed by RNA extraction and  q-PCR  analysis for top ten upregulated transcription factors. n = 3 independent samples. Results of relative fold changes are shown as means ± SD. **P < 0.01 by two-tailed Student's t-test.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(D) Immunoblotting  analysis of Ddx3y  in RNA pull-down  samples by Atf4  sense, antisense and control probes in mice ISCs. (E) Immunoblotting  analysis of Ddx3y  in RNA  pull-down samples by Atf4  and control probes in circBtnl1+/+ and circBtnl1-/- mice ISCs.",
    "ncbi_link": "Atf4: 11911
Btnl1: 100038862"
  },
  {
    "caption": "(J) Confocal microscopy  of ATF4  in Ddx3y  knockdown and overexpression organoids from circBtnl1+/+ and circBtnl1-/- mice. Scale bars, 20 μm.",
    "ncbi_link": "Btnl1: 100038862
Ddx3y: 26900"
  },
  {
    "caption": "(K, L) Expression levels of Ddx3y  and Atf4  in circBtnl1+/+ and circBtnl1-/- ISCs  were examined by  real-time PCR (K) and Western blot  (L), three independent experiments were performed. Results of relative fold changes are shown as means ± SD. ** P < 0.01, NS, not significant, by two-tailed Student's t-test.",
    "ncbi_link": "Atf4: 11911
Btnl1: 100038862
Ddx3y: 26900"
  },
  {
    "caption": "(D, E) ChIP  assay was performed using anti-H3K4me3 (D) or anti-H3K27me3 (E) with circBtnl1+/+ and circBtnl1-/- ISCs  lysates. **P < 0.01 by two-tailed Student's t-test. Data are representative of at least three independent experiments.",
    "ncbi_link": "Btnl1: 100038862"
  },
  {
    "caption": "(H) Confocal microscopy of Sox9  in Atf4  knockdown (Atf4  KD) organoids from circBtnl1+/+ and circBtnl1-/- mice. Scale bars, 30 μm.",
    "ncbi_link": "Atf4: 11911
Btnl1: 100038862"
  },
  {
    "caption": "(F) Representative organoid  images of circBtnl1+/+; sgSox9 and circBtnl1-/-; sgSox9 mice, sgCtrl served as control. Organoid  formation  ratios (n = 3) are shown. Organoid  formation  ratios are shown as mean ± s. d. *P < 0.05 by two-tailed Student's t-test. Scale bars, 200 μm.",
    "ncbi_link": "Btnl1: 100038862
Sox9: 20682"
  },
  {
    "caption": "okp1-R164C suppressed the temperature-sensitive growth defect of cbf1∆ cse4-R37A. Serial dilutions of strains with the indicated genotypes were spotted on full medium and grown for three days at 30ºC or 37ºC. The original okp1-R164C isolate from the suppressor screen is indicated as \"UV mutagenesis\".",
    "ncbi_link": "cbf1: 853523
cse4: 853817
okp1: 853090"
  },
  {
    "caption": "Serial dilutions of strains with the indicated genotypes were spotted on full medium and grown for three days at 30ºC or 37ºC. The original okp1-R164C isolate from the suppressor screen is indicated as \"UV mutagenesis\". okp1-R164C suppressed the growth defect of cse4-R37A with chl4∆.",
    "ncbi_link": "chl4: 851841
cse4: 853817
okp1: 853090"
  },
  {
    "caption": "okp1-R164C was unable to suppress the lethality of cse4-R37A with ame1-4. Tetrad dissection of a genetic cross between a cse4-R37A okp1-R164C and an ame1-4 strain is shown. The four spores from individual asci are aligned in vertical rows.",
    "ncbi_link": "ame1: 852512
cse4: 853817
okp1: 853090"
  },
  {
    "caption": "okp1-R164C suppressed the maintenance defect of cse4-R37A for plasmids lacking the CDEI sequence of CEN6 (CEN ∆CDEI, at 37ºC). Error bars give SD of at least three independent transformants. * p = 0.03.",
    "ncbi_link": "cse4: 853817
okp1: 853090"
  },
  {
    "caption": "The okp1 mutations I45T, S94T and E208V suppressed the temperature-sensitive growth defect of cbf1∆ cse4-R37A. Strains with the indicated okp1 alleles on a plasmid (derivatives of AEY5584)",
    "ncbi_link": "cbf1: 853523
cse4: 853817
okp1: 853090"
  },
  {
    "caption": "okp1-R164C restored binding of Okp1 to centromeric sequences. ChIP of 9xmyc-tagged Okp1 was performed in strains with the indicated genotypes that were grown at 37ºC for 4 hours before ChIP. Enrichment of CEN4 and POL1 (as a control) relative to input is given. Below, Western blot analysis of the amounts of 9xmyc-Okp1 and histone H2B (loading control) in whole cell extracts.",
    "ncbi_link": "POL1: 
okp1: 853090"
  },
  {
    "caption": "okp1-R164C restored binding of Ame1 to centromeric sequences. ChIP of 9xmyc-tagged Ame1 was performed as in (A). Below, Western blot analysis of the amounts of 9xmyc-Ame1 and H2B as in (A).",
    "ncbi_link": "okp1: 853090"
  },
  {
    "caption": "okp1-R164C restored binding of Mtw1 to centromeric sequences. ChIP of 9xmyc-Mtw1 and Western blots (right)",
    "ncbi_link": "okp1: 853090"
  },
  {
    "caption": "okp1-R164C improved in vivo association of Okp1 with Cse4-R37A. Co-immunoprecipitation of Cse4-R37A and Okp1 was carried out in cells carrying cse4-R37A with (+) or without (-) 3xHA-tag and OKP1 or okp1-R164C with (+) or without (-) 9xmyc-tag (AEY5040, AEY5972, AEY5973, AEY6589, AEY6592). Cells were grown at 23ºC or were shifted to 37ºC for 5 hours prior to harvesting. Cse4-R37A was immunoprecipitated using an α-HA antibody, and the presence of Cse4-R37A and Okp1 or Okp1-R164C in the immunoprecipitate was tested by Western blotting with α-HA and α-myc antibody, respectively. Left, inputs (the two bands indicate Okp1 and a shorter degradation product); right, α-HA immunoprecipitates.",
    "ncbi_link": "HA: 
myc: 
cse4: 853817
OKP1: 853090
okp1: 853090"
  },
  {
    "caption": "The ame1 mutations S59P, N159H, S275N and a C-terminal truncation after aa 273 (ame1-273*) suppressed the growth defect of cbf1∆ cse4-R37A. cbf1∆ cse4-R37A ame1∆ strains carrying the indicated plasmid-borne ame1 alleles",
    "ncbi_link": "ame1: 852512
cbf1: 853523
cse4: 853817"
  },
  {
    "caption": "Mimicking the unacetylated state of Cse4-K49 (cse4-K49R) partially suppressed the temperature-sensitivity of cbf1∆ cse4-R37A. cbf1∆ cse4∆ strains carrying the indicated cse4 alleles on a plasmid were spotted on full medium and grown",
    "ncbi_link": "cbf1: 853523
cse4: 853817
Cse4: 853817"
  },
  {
    "caption": "cse4-K49R suppressed the lethality of cse4-R37A with ctf19∆. Tetrad dissection of a ctf19∆ strain crossed with cse4-R37A (left) and cse4-R37A K49R (right). Representation",
    "ncbi_link": "cse4: 853817
ctf19: 856089"
  },
  {
    "caption": "Acetylation of Cse4-K49 was reduced in the absence of Gcn5 and the SAGA complex, but not in the absence of the HAT Sas2. Cse4 was precipitated as in (A) from strains wild-type (wt) or gcn5∆ (top) or sas2∆ strains (bottom) carrying HA-tagged Cse4. w/o, control immunoprecipitation without antibody.",
    "ncbi_link": "HA: 
Cse4: 853817
Gcn5: 853167
gcn5: 853167
Sas2: 855157
sas2: 855157"
  },
  {
    "caption": "Cse4-K49Ac depended on the SAGA components Ada2 and Spt7. Cse4-K49Ac was determined as in (A, left) with cells carrying ada2∆ or spt7∆.",
    "ncbi_link": "Ada2: 852059
ada2: 852059
spt7: 852373
Spt7: 852373"
  },
  {
    "caption": " WT and hCDC14APD RPE1 cells were serum starved for 48 h for inducing ciliogenesis prior to fixation. Cilia were stained with Arl13B (green) while the basal bodies were marked with C-Nap1 (red). DNA was stained with DAPI. Cilia in the magenta box are shown enlarged on the right picture ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " WT and hCDC14APD RPE1 cells were serum starved for 48 h for inducing ciliogenesis prior to fixation. Cilia were stained with Arl13B (green) while the basal bodies were marked with C-Nap1 (red). DNA was stained with DAPI Percent of ciliated cells, as well as the length of cilia, was quantified from A. Cilia length was measured by a semi-automated ImageJ macro as described in methods. Data points are the average of three independent experiments with N = 150 cilia for each experiment and condition. Error bars represent the mean ± SD. **** P≤ 0.0001. High means 80-90% and low 40-50% confluency of RPE1 cells",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " Elongated cilia phenotype was confirmed by siRNA-mediated knockdown of hCDC14A. Three independent experiments, N = 150 cilia for each experiment and condition. Mean ± SD. **** P≤ 0.0001 ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " hCDC14A-GFP and hCDC14AC278S-GFP under control of the TetON promoter were stably integrated into RPE1 cells. hCDC14A-GFP and hCDC14AC278S-GFP localized to the C-Nap1 marked basal body upon Dox induction. In addition, expression of hCDC14A-GFP but not the phosphatase dead hCDC14AC278S-GFP mutant inhibited cilia formation. Ciliated cells were quantified 48 h after serum starvation with and without Dox addition. Three independent experiments; N = 150 cilia for each experiment and condition. Mean ± SD. *** P≤ 0.001; ns: not significant ",
    "ncbi_link": "GFP: 
hCDC14A: 8556"
  },
  {
    "caption": " RPE1 cells over-expressing hCDC14AC278S have longer cilia than those over-expressing hCDC14A. Three independent experiments, N = 100 cilia for hCDC14A expressing cells and 200 for hCDC14AC278S expressing cells. Mean ± SD. *** P≤ 0.001 ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " The dynamics of ciliogenesis was determined by serum starving WT and hCDC14APD cells for different time-points. The cilia from hCDC14APD cells continue to elongate even after 48 h of starvation whereas those from WT cells reached constant length within 12 to 24 h. Three independent experiments; N = 150 cilia for each experiment and condition. Mean ± SEM. * P≤ 0.05, **; P≤ 0.01; **** P≤ 0.0001",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " In a time course experiment, the cilia disassembly kinetics was measured by first inducing ciliation through 48 h of serum starvation prior to incubation with serum containing media for different time points. Measurement of cilia length indicated the comparable rates of cilia disassembly in RPE1 WT and hCDC14APD cells. Cilia disassembly rates are shown in Fig. EV1D. Three independent experiments, N = 150 cilia for each experiment and condition. Mean ± SEM. **** P<0.0001 ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " Images of cilia of WT RPE1 and hCDC14APD RPE1 cells from I, 0, 6 and 24 h after serum addition. Fixed cells were analyzed for cilia length ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": "TetON-hCDC14A-GFP RPE1 cells were serum starved for 48 h prior to fixation and immunofluorescence microscopy. hCDC14A-GFP colocalizes with Phalloidin 555 conjugated dye that marks F-actin fibers. The boxed area was 10-fold enlarged and displayed below the corresponding images to indicate co-localization of hCDC14A-GFP and F-actin. Line scan inside the magenta colored box showed in (A)",
    "ncbi_link": "GFP: 
hCDC14A: 8556"
  },
  {
    "caption": "hCDC14A, not the inactive hCDC14AC278S, dephosphorylates the serine residue 142 of DBN1 in vivo. RPE1 cells expressing GFP, hCDC14A-GFP, and hCDC14AC278S-GFP under TetON promoter were serum starved in presence or absence of Dox for 48 h prior to fixation for immunofluorescence. DBN1pS142 was detected with a phospho-specific antibody. DNA was stained with DAPI. Scale Bar = 10 μm",
    "ncbi_link": "GFP: 
hCDC14A: 8556"
  },
  {
    "caption": "DBN1S142 was hyper-phosphorylated in hCDC14APD cell lines during ciliogenesis compared to the WT control. In this experiment we sequentially analyzed DBN1pS142 and DBN1 on the same blot. The specificity of the DBN1pS142 antibody was validated by siRNA mediated knock-down of DBN1 in both hCDC14APD cells and GFP/hCDC14A-GFP/hCDC14AC278S-GFP stable cell lines. Three independent experiments. Mean ± SD. ** P≤ 0.01, *** P≤ 0.001",
    "ncbi_link": "GFP: 
hCDC14A: 8556
DBN1: 1627"
  },
  {
    "caption": "In vitro dephosphorylation of DBN1 by purified hCDC14A. DBN1-GFP was transfected into HEK293T cells and expressed for 48 h. DBN1-GFP was immunoprecipitated from cell lysates with GFP binder. The immunoprecipitated phospho-DBN1 was then incubated with and without recombinant hCDC14A in vitro. The DBN1pS142/DBN1 ratio was densitometrically measured. Three independent experiments. Mean ± SD. **** P≤ 0.0001",
    "ncbi_link": "DBN1: 
GFP: "
  },
  {
    "caption": "One targeted clone from each gRNA (1.16, 2.18, 3.3) including the non-targeted clone 2.19 and WT control were serum starved for 48 h to induce ciliogenesis. Subsequently, cilia length was measured. The cilia from DBN1 KO cells were significantly longer than those from WT or non-targeted controls. Three independent experiments; N = 150 cilia for each experiment and condition. Mean ± SD. **** P≤ 0.0001.",
    "ncbi_link": "DBN1: 1627"
  },
  {
    "caption": "Overexpression of DBN1, DBN1S142A and DBN1S142D in RPE1 WT cells. Three independent experiments, N = 150 cilia for each experiment and condition. Mean ± SD. ** P≤ 0.01; *** P≤ 0.001; ns: not specific.",
    "ncbi_link": "DBN1: 1627"
  },
  {
    "caption": " The phospho-inhibitory (S142A) version of DBN1 rescued the elongated cilia of DBN1 KO cells. Three independent experiments, N = 150 cilia for each experiment and condition. Mean ± SD. * P≤ 0.05; *** P≤ 0.001; ns: not significant. Pairwise comparison was done with unpaired student's t-test and the p-value was written in the figure. Global comparison was done with one-way ANOVA and the p-values were marked with stars. ",
    "ncbi_link": "DBN1: 1627"
  },
  {
    "caption": " The overexpressed WT DBN1 was hyper-phosphorylated in cells as detected by phospho-specific DBN1pS142 antibodies. The DBN1pS142 antibodies did not detect the overexpressed DBN1S142A or DBN1S142D. ",
    "ncbi_link": "DBN1: 1627"
  },
  {
    "caption": " Immunoblot analysis confirming the successful siRNA depletion of CDK5 and indicating hypo-phosphorylation of DBN1S142 in response to CDK5 depletion The DBN1pS142/GAPDH ratio from (H) was densitometrically measured. Three independent experiments. Mean ± SD. * P≤ 0.05 ",
    "ncbi_link": "CDK5: 1020"
  },
  {
    "caption": "Depletion of CDK5 decreased the cilia length in WT cells. It restored cilia length in hCDC14APD cells. Three independent experiments; N = 150 cilia for each experiment and condition. Mean ± SD. **; P≤ 0.01; **** P≤ 0.0001; ns: not significant.",
    "ncbi_link": "hCDC14A: 8556
CDK5: 1020"
  },
  {
    "caption": "CDK5 mediated cilia length decrease can be completely blocked by expression of the phospho-mimetic DBN1S142D in hCDC14APD cells. Three independent experiments; 150 cells per experiment and condition. Mean ± SD; ns = not significant; **** P≤ 0.0001.",
    "ncbi_link": "hCDC14A: 8556
CDK5: 1020
DBN1: 1627"
  },
  {
    "caption": " hCDC14APD cells showed an increased localization of myosin Va containing vesicles within the 1 μm-radius of the basal body (red cicle). The encircled area in MERGE is shown 4-fold enlarged on the right hand side of the figure Quantification of C. Data was calculated from a total of 180 cells pooled from three independent experiments. Mean ± SD. * P≤ 0.05, *** P≤ 0.001, **** P≤ 0.0001 ",
    "ncbi_link": "hCDC14A: 8556"
  },
  {
    "caption": " Arp2 localization in REP1 WT, hCDC14APD and DBN1 KO cells. Signal intensity was measured 30 min after serum starvation. The encircled area in MERGE is shown 4-fold enlarged on the right hand side of the figure ",
    "ncbi_link": "hCDC14A: 8556
DBN1: 1627"
  },
  {
    "caption": " Quantification of E. Sub-centrosomal (1 μm-radius; red circle in E) Arp2 was measured by quantifying the intensity of Arp2 in WT, hCDC14APD and DBN1 KO cells. Both hCDC14APD and DBN1 KO cells contain significantly higher Arp2 in the pericentrosomal area (1 μm-radius) compared to WT cells after 30 min of serum starvation. Data were calculated from a total of 120 cells pooled from three independent experiments. Mean ± SD. **** P≤ 0.0001 ",
    "ncbi_link": "hCDC14A: 8556
DBN1: 1627"
  },
  {
    "caption": " Pericentrosomal ARP2 enrichment was comparable in the RPE1 DBN1 KO cells (Tet Control) with DBN1 KO cells expressing different DBN1 versions (WT, S142A, S142D). Data were calculated from a total of 200 cells each pooled from two independent experiments. Mean ± SD. ns: not specific ",
    "ncbi_link": "DBN1: 1627"
  },
  {
    "caption": "C Firefly luciferase expression of constructs that contain distal and proximal enhancers of OCT4 after transfection of pRh6 and 2a2iL-RH6. The ratio of firefly luciferase expression to Renilla luciferase expression (expressed from co-transfected plasmid) measured 48 h after transfection showed proximal enhancer activity in pRH6 and distal enhancer activation in 2a2iL-RH6. OCT4 PE-Luc ***P<0.001, OCT4 DE-Luc *P<0.05 (t-test). Data presented as mean ± SD (n=3).",
    "ncbi_link": "Luc: 
luciferase: 
OCT4: 5460"
  },
  {
    "caption": " B ATAC-Seq genome tracks showing three signature peaks located near the genes SAE1, RAG1, and CD8A. Framed regions indicate cell-type-specific signature ATAC-Seq peaks. Blue triangles indicate known promoter or enhancer regions, which are annotated in the GeneHancer (GH) Regulatory Elements database ",
    "ncbi_link": "CD8A: 925
RAG1: 5896
SAE1: 10055"
  },
  {
    "caption": "A The rationale of footprinting analysis as illustrated by actual ATAC-Seq peaks, HINT-ATAC footprint hits, and example TF motif instances near RAG1 gene in DN2 population of thymus donor 6.",
    "ncbi_link": "RAG1: 5896"
  },
  {
    "caption": "D Heatmap of VST normalized read counts (each row is also normalized by the row mean) of differentially expressed genes (pval<0.1; DESeq2) in three patients in comparison to remaining 16. Orange triangles indicate three patients with no DAB1 but high SPI1 expression and motif counts.",
    "ncbi_link": "DAB1: 1600
SPI1: 6688"
  },
  {
    "caption": "A) Immunoblot analyses showing MAPK phosphorylation after flg22 induction in Col-0 and in mkkk7. Protein extracts were made from seedlings treated with 1 μM flg22 and samples were taken at t=0, 10 and 30 min post induction. The p44/42 antibody was used to detect phosphorylated MAPKs. Position of the individual phosphorylated MAPKs is indicated at the right. Equal loading of proteins is shown with an α-Actin antibody as a loading control (bottom panel). Three biological replicates were done with identical results",
    "ncbi_link": "mkkk7: 820555"
  },
  {
    "caption": "B) MPK6 phosphorylation is specifically enhanced in mkkk7. Comparison of phosphopeptide abundances from selected MAP kinases in Col-0 (blue) and mkkk7 (red) seedlings at t = 0 min and t = 10 min after 1 μM flagellin treatment by selected reaction monitoring (SRM) mass spectrometry. Phosphopeptide corresponding to MKKK7 are only detectable in Col-0 seedlings and are non-detectable (ND) in mkkk7. Bars represent means of measured peptide areas (sum of all transition areas) for three biological replicates, with error bars ± SEM (n=3). Asterisks indicate significant difference between Col-0 and mkkk7 at individual time points (student t-test, *>0.05, **>0.01 and ***>0.001). ND indicates integration of an area without transitions significantly above background. Above each graph the protein name and the phosphorylated residue (in brackets) is indicated as well as the corresponding phosphopeptide sequence. Serine (S), Threonine (T) or Tyrosine (Y) phosphorylation is indicated by \"[+80]\".",
    "ncbi_link": "mkkk7: 820555"
  },
  {
    "caption": "A) Transient expression analysis in Arabidopsis mesophyll protoplasts shows enhanced defense gene expression in mkkk7 protoplasts after flg22 treatment. Protoplasts were isolated from 4 week old plants and transfected with pWRKY29:fLUC (WRKY29) or pFRK1:fLUC(FRK1) constructs together with 35S:rLUC, as indicated in the graph. Protoplasts were treated for 4 hrs with 10 µM flg22 or mock treated as indicated. The horizontal axis indicates the treatment while the vertical axis represents expression levels relative to the mock treated control sample, as fold induction. All measurements were normalized to the rLUC activity. Bars represent means ± STDEV (n=2). Experiment was repeated 6 times with similar results.",
    "ncbi_link": "35S: 
LUC: 
FRK1: 816436
mkkk7: 820555
WRKY29: 828455"
  },
  {
    "caption": "B) WRKY29 transcripts measured by qRT-PCR in flg22 treated leaf material. Leaf strips of Col-0 and mkkk7 were treated with 1 µM flg22 for t=0, 1, 2, and 4h. WRKY29 transcripts were normalized against Ubiquitin transcript as described before [62]. Bars represent mean value and error bars show SE (n=3). (* p<0.05, ** p<0.01, student t-test).",
    "ncbi_link": "Ubiquitin: 
mkkk7: 820555
WRKY29: 828455"
  },
  {
    "caption": "C) FRK1 transcripts measured by qRT-PCR in flg22 treated leaf material. Leaf strips of Col-0 and mkkk7 were treated with 1 µM flg22 fort=0, 1, 2, and 4h. FRK1 transcripts were normalized against Ubiquitin transcript as described before [62]. Bars represent mean value and error bars show SE (n=3). (* p<0.05, ** p<0.01, student t-test).",
    "ncbi_link": "Ubiquitin: 
FRK1: 816436
mkkk7: 820555"
  },
  {
    "caption": "A) Transient co-expression of MKKK7 in Arabidopsis mesophyll protoplasts shows suppression of flg22-induced WRKY29 gene expression. Protoplasts were transfected with pWRKY29:fLUC, 35S:rLUC and indicated overexpression constructs of MKKK7 (OE-MKKK7, OE-MKKK7AA or OE-MKKK7DD) as indicated on the horizontal axis. Protoplasts were treated with 10 μM flg22 or mock treated for 4 hrs. All measurements were normalized to the rLUC activity and expression is relative to the mock treated control sample, shown as fold induction on the vertical axis. Results shown are means ± STDEV (n=2). At least two biological replicates were done with similar results",
    "ncbi_link": "35S: 
LUC: 
MKKK7: 820555
WRKY29: 828455"
  },
  {
    "caption": "B) Quantification of bacterial growth in Arabidopsis lines Col-0, mkkk7 and p35S:MKKK7-GFP in the mkkk7 background. Four to five-week-old plants were pressure-infiltrated with virulent Pst DC3000 and at indicated time points 6 samples were harvested and bacteria re-isolated on selective media. The number of colony forming units (cfu/cm2) was determined at t=0, 2 and 3days post inoculation (dpi). Data represents mean values ± SEM (n=6; **, p<0.01; paired t-test). Experiments were done at least twice with similar results.",
    "ncbi_link": "35S: 
mkkk7: 820555
MKKK7: 820555"
  },
  {
    "caption": "C) Disease symptom development in Pst-infected lines with estradiol inducible constructs of ind-MKKK7AA L8, ind-MKKK7AA L10, ind-MKKK7DD L1 and ind-MKKK7DD L3. Two independent transgenic lines for each construct were grown under short-day conditions and disease symptoms were scored 3 dpi. Data represents mean values ± SEM (n=20; *, p<0.05; **, p<0.01; paired t-test). The vertical axis represents the percentage disease symptoms. Experiments were done at least twice with similar results.",
    "ncbi_link": "MKKK7: 820555"
  },
  {
    "caption": "A) Effect of 100 nM flg22 treatment on ROS burst measured in 5 week old plants of Col-0 and mkkk7.",
    "ncbi_link": "mkkk7: 820555"
  },
  {
    "caption": "B) Effect of 100 nM flg22 treatment on the ROS burst measured in 5 week old plants of Col-0 and two independent inducible MKKK7AA transgenic lines.",
    "ncbi_link": "MKKK7: 820555"
  },
  {
    "caption": "C) Effect of 100 nM flg22 treatment on the ROS burst measured in 5 weeks old plants of Col-0 and two independent inducible MKKK7DD transgenic lines. Graphs represent means with error bars ± SEM (n=24). The vertical axis represents the relative increase in ROS production (photon counts) after PAMP treatment. At least three biological replicate experiments were done with similar results.",
    "ncbi_link": "MKKK7: 820555"
  },
  {
    "caption": "Scatter plot elucidating fold change (FC) in gene expression between samples treated with JNKi compared to vehicle (Y-axis) and expression of constitutively active JNK (MKK7-JNK) versus vector control (X-axis) from biological triplicates. Representative examples of genes that are specifically induced by JNK in metastatic breast cancer cells are highlighted in red.",
    "ncbi_link": "MKK7: 26400
JNK: 5599"
  },
  {
    "caption": "GSEA graphs showing (C) enrichment of a mammary stem cell signature (Pece et al, 2010) in MDA231-LM2 cancer cells expressing MKK7-JNK NES, normalized enrichment score.",
    "ncbi_link": "MKK7: 26400
JNK: 5599"
  },
  {
    "caption": "GSEA showing significant enrichment of four distinct signatures of mammary stem cells within data sets from MDA231-LM2 cells either expressing MKK7-JNK or treated with JNKi. Mammary stem cell signatures are indicated as follows: a, up in mammary stem cells b, up in fetal mammary stem cells ; c, up in adult mammary stem cells and d, up in mammary repopulating units",
    "ncbi_link": "MKK7: 26400
JNK: 5599"
  },
  {
    "caption": "Heat map of the JNK signature composed of 68 genes that are induced by expression of MKK7-JNK and repressed by JNKi,",
    "ncbi_link": "MKK7: 26400
JNK: 5599"
  },
  {
    "caption": "Generation of oncospheres in SUM159 cells expressing constitutively active JNK or inactive mutated JNK. Values are mean from 10 wells per group ± SD.",
    "ncbi_link": "JNK: 5599"
  },
  {
    "caption": "SPP1 and TNC expression in the indicated breast cancer cells treated with increasing concentrations of JNKi.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in MDA231-LM2 cells transduced with pLVX-puro lentivirus without a transgene (control) or expressing constitutively-active JNK (MKK7-JNK) or mutated inactive JNK (MKK7-JNK(mut)).",
    "ncbi_link": "MKK7: 26400
JNK: 5599
SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in pleural effusion (1 and 2) and ascites (3 and 4) samples from four different patients treated with JNKi (4 μM, 48h) in culture. Values are mean ± SD from triplicates. The results from all four patient samples were included to calculate significance of JNKi on gene expression. SPP1, P = 0.0079; TNC, P = 0.0002.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "Analysis of SPP1 and TNC mRNA levels in SUM159-LM1 cells grown as monolayer or spheres and treated with vehicle or JNKi. For panels A-D, values represent the mean of qPCR triplicates ± SD.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "ChIP analysis of c-Jun binding to sequences in SPP1 or TNC promoters. Analysis of SPP1 and TNC promoter fragments pulled down by c-Jun and IgG antibodies. Values represent the mean of qPCR triplicates ± SD.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "Correlation analysis of SPP1 and TNC with JUN expression in dissected metastatic nodules from breast cancer patients (GSE14020). N = 65 metastasis samples.",
    "ncbi_link": "JUN: 3725
SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "Lung metastasis in Spp1+/- mice implanted with MDA231-LM2 cells expressing control shRNA (control), and Spp1-/- mice implanted with MDA231-LM2 cells independently expressing one of two different SPP1 shRNAs (SPP1-deficient). Ex vivo lung luminescence was analyzed, panel H. Boxes show the median value with upper and lower quartiles. Whiskers represent minimum and maximum values. Control n = 16 mice, SPP1 deficient (1) n = 14 mice and SPP1 deficient (2) n = 15 mice. P values were determined by a two-tailed Mann-Whitney test. (I) Representative histological images of metastatic foci (top) and ex vivo lung bioluminescence (bottom). In histological samples, immunohistochemistry was used to determine metastatic nodules based on expression of human vimentin (arrows). Scale bar, 100 µm.",
    "ncbi_link": "Spp1: 20750
SPP1: 20750"
  },
  {
    "caption": "SUM159-LM1 cells expressing either control shRNA (control), or one of two different TNC shRNAs (shTNC 1 and 2), were injected intravenously into NSG mice. (J) Metastatic colonization was quantified by lung bioluminescence. Control and shTNC (1) n = 8 mice per group, shTNC (2) n = 7 mice. P value was determined by a two-tailed Mann-Whitney test. (K) Representative images of metastatic foci (top) and ex vivo lung bioluminescence (bottom). Arrows denote vimentin-expressing cancer cells in metastases.",
    "ncbi_link": "TNC: 21923"
  },
  {
    "caption": "Kaplan-Meier analysis of breast cancer patients (combined GSE2603 and GSE5327 datasets) showing a link between high SPP1 and TNC expression and poor lung metastasis-free survival. Patient samples, SPP1 and TNC low n = 70; SPP1 and TNC high n = 70. HR, Hazard ratio.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in SUM159-LM1 cells treated with increasing concentrations of PAX qPCR triplicates ± SD.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in SUM159-LM1 cells treated with increasing concentrations of doxorubicin (DOXO). qPCR triplicates ± SD.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in SUM159-LM1 cancer cells treated with 4 μM 5-Fluorouracil or 4 μM methotrexate. Cells were treated for 48 hours. qPCR triplicates ± SD.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "SPP1 and TNC expression in SUM159-LM1 cells treated with paclitaxel and JNKi. qPCR triplicates ± SD. SPP1 and TNC repression by JNKi, P < 0.05 for both vehicle and PAX-treated cells.",
    "ncbi_link": "SPP1: 6696
TNC: 3371"
  },
  {
    "caption": "Growth curves of mammary tumors in vehicle- or PAX-treated Spp1+/- mice implanted with the indicated cells expressing control shRNA, and Spp1-/- mice implanted with the indicated cells expressing SPP1 shRNA. MDA231-LM2: control, PAX and SPP1 def. + PAX n = 16 tumors per group, SPP1 def. n = 14 tumors. SUM159-LM1: control, PAX and SPP1 def. + PAX n = 16 tumors per group, SPP1 def. n = 15 tumors.",
    "ncbi_link": "SPP1: 20750
Spp1: 20750"
  },
  {
    "caption": "Quantification of lung metastasis from the animals described in panels A and B. The number of metastatic foci per field of view (FOV) or per lung section (LS) was determined. MDA231-LM2 tumor-bearing mice: control, PAX and SPP1 def. + PAX n = 8 mice per group, SPP1 def. n = 7 mice. SUM159-LM1 tumor-bearing mice: control, PAX and SPP1 def. + PAX n = 8 mice per group, SPP1 def. n = 7 mice.",
    "ncbi_link": "SPP1: 20750"
  },
  {
    "caption": "Tumor weight in mice at day 40 after implantation of MDA231-LM2 breast cancer cells in a control or SPP1 deficient setting undergoing combination treatment with doxorubicin (Adriamycin) and cyclophosphamide (AC regimen). Control, AC and SPP1 def. n = 16 tumors per group, SPP1 def. + AC n = 14 tumors.",
    "ncbi_link": "SPP1: 20750"
  },
  {
    "caption": "Mammary tumor growth curves in PAX-treated NSG mice bearing control or TNC knockdown MDA231-LM2 tumors. Values are means ± SEM, n = 16 tumors per group. **** P < 0.0001. Lung metastases quantified in tumor bearing mice",
    "ncbi_link": "TNC: 21923"
  },
  {
    "caption": "(c) Pathogenic Parkin mutations abrogate mitochondrial translocation and/or clearance. HeLa cells transfected with Flag-Parkin wild-type or pathogenic mutants were treated with CCCP and stained with anti-Flag (green), anti-TOM20 (red) and Hoechst33342 (blue). Representative merged images are shown. Scale bars, 10 μm. Immunostaining of cells transfected with non-functional cysteine mutants and functional Parkin variants is shown in Supplementary Information, Fig. S1a and S1b, respectively.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(d, e) Based on the mitochondrial effects, Parkin mutants can be classified into functional and non-functional classes. (d) Quantification of Parkin translocation to damaged mitochondria after 2 h of CCCP treatment, as defined by complete colocalization of Parkin with the mitochondrial marker (n = 3). (e) Quantification of cells with uncleared mitochondria after 24 h of CCCP treatment, as shown by complete loss of mitochondrial staining (n = 3). Data represent the mean ± s.d., *P ≤ 0.05, **P ≤ 0.005, ***P ≤ 0.0005 compared with wild-type. WT, wild-type.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "Stable Parkin wild-type or pathogenic mutants expressing SH-SY5Y cell lines were induced with doxycycline (DOX) for 72 h and treated with CCCP for the indicated times. Cells were stained with anti-Parkin (green), anti-TOM20 (red) and Hoechst33342 (blue). (a-b) CCCP treatment of stable SH-SY5Y cells for 0 h. Unstimulated control cells (- DOX) show relatively low levels of endogenous Parkin, compared to cells with induced expression of Parkin wild-type or K161N, R275W and G430D mutants (+ DOX). Immunostaining (a) and western blot analysis (b) of the induced cells demonstrate comparable levels of Parkin expression in the selected clones. β-Actin served as a loading control.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c, d) After 2 h of CCCP treatment, massive colocalization of wild-type Parkin and mitochondrial clusters can be observed in the induced cells when compared with unstimulated controls. Similarly, Parkin K161N and R275W mutants translocate to mitochondria, whereas G430D does not.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(e, f) After 24 h of CCCP treatment, induced wild-type Parkin-expressing cells show full clearance of damaged mitochondria. In contrast, the pathogenic mutants analysed fail to execute mitophagy and, therefore, damaged mitochondria remain uncleared. Representative images of three independent experiments are shown. Scale bars, 10 μm (a, c and e). (d, f) Quantifications of the observed mitochondrial effects in Parkin-expressing SH-SY5Y cells (n = 3). Data represent the mean ± s.d., ***P ≤ 0.0005 compared with induced wild-type Parkin. WT, wild-type.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c) Western blot of PINK1 siRNA-transfected HeLa cells used in d-h demonstrates the knockdown efficiency and specificity of PINK1 silencing.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "d-h) PINK1-specific siRNA abrogates Parkin translocation to mitochondria after 2 h, and mitochondrial clearance after 24 h, of CCCP treatment. This can be rescued by re-transfection with wild-type PINK1, but not with a kinase-dead mutant or a PINK1 variant lacking the MTS. Control siRNA- or PINK1 siRNA-silenced HeLa cells were transfected with EGFP-Parkin wild-type and PINK1-V5 wild-type, 3×KD or ΔMTS mutants. Use of appropriate empty vector controls is depicted. Cells were treated with CCCP and stained with anti-TOM20 (pseudo coloured; blue) and anti-V5 (red) to visualize mitochondrial morphology and re-transfected PINK1, respectively. Wild-type Parkin was visualized by EGFP epifluorescence (green). Parkin-positive cells are surrounded by a line. Representative images of four independent experiments are shown. Scale bars, 10 μm.",
    "ncbi_link": "Parkin: 5071
PINK1: 65018"
  },
  {
    "caption": "a, b) Stable Mito-DsRed (pseudo coloured; blue)-expressing HeLa cells were transfected with Flag-Parkin wild-type or pathogenic mutants. Cells were treated with CCCP before immunostaining of Parkin with anti-Flag (green) and endogenous poly-ubiquitin with a specific antibody FK1 (red). (a) In contrast to pathogenic mutations, wild-type Parkin shows colocalization with poly-ubiquitin after 6 h of CCCP treatment at the site of condensed mitochondria. (b) After 24 h of CCCP treatment, K161N and R275W Parkin mutants colocalize with both poly-ubiquitin and mitochondria. In contrast, translocation-deficient Parkin mutants K211N, T240R and G430D lack the mitochondria-associated poly-ubiquitin signal. Representative images are shown. Scale bars, 10 μm. Complementary Parkin of untreated cells and quantification of colocalization of Parkin, mitochondria and poly-ubiquitin upon CCCP treatment are shown in Supplementary Information, Fig. S3a, b and c, respectively.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c, d) Parkin-directed mitophagy specifically involves linkage of ubiquitin through lysines 27 and 63. HeLa cells were transfected with EGFP-Parkin wild-type and ubiquitin lysine variants and treated with CCCP before immunostaining with anti-HtrA2/Omi, as a mitochondrial marker (pseudo coloured; blue) and anti-His (red) to detect ectopic ubiquitin. Parkin was visualized by its fusion to EGFP (green). (c) Note that only wild-type, K27 and K63 6×His-tagged ubiquitin variants are colocalized with condensed mitochondria and EGFP-Parkin after 6 h of CCCP treatment. All other ubiquitin mutants interfere with Parkin translocation to mitochondria. (d) Only co-expression of K27 or K63 ubiquitin recapitulates mitochondrial clearance similarly to 6×His-tagged wild-type ubiquitin after 24 h of CCCP treatment. Representative images are shown. Scale bars, 10 μm. Immunostaining of untreated cells and all other ubiquitin variant combinations tested are shown in Supplementary Information, Fig. S4a and b, c, respectively. WT, wild-type; PolyUb, poly-ubiquitin.",
    "ncbi_link": "ubiquitin: 6233///7311///7316"
  },
  {
    "caption": "(a, b) Stable Mito-DsRed (pseudo coloured; blue)-expressing HeLa cells were transfected with Flag-Parkin wild-type or pathogenic mutants. Cells were treated with CCCP for the indicated times before immunostaining with anti-Flag (green) and anti-p62 (red). (a) In contrast to the pathogenic mutants, wild-type Parkin colocalizes with p62 at the site of clustered mitochondria, after 6 h of CCCP treatment. (b) After 24 h of CCCP treatment, wild-type Parkin-transfected cells show complete loss of mitochondria, whereas K161N and R275W Parkin mutants colocalize with both p62 and mitochondria. In contrast, translocation-compromised mutants K211N, T240R and G430D, lacking the mitochondria-associated poly-ubiquitin signal (Fig. 4b), did not colocalize with p62. Representative images of four independent experiments are shown. Data from untreated control cells and quantification of colocalization of Parkin, mitochondria and p62 upon CCCP treatment are shown in Supplementary Information, Fig. 5a and b, c, respectively.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c, d) Control siRNA- or p62 siRNA-silenced HeLa cells were transfected with EGFP-Parkin wild-type. Cells were treated with CCCP for the indicated times and stained with anti-TOM20 (pseudo coloured; blue) to visualize mitochondrial morphology and anti-p62 (red) to monitor silencing efficiency. Parkin wild-type was visualized by EGFP epifluorescence (green). Parkin-positive cells with cleared mitochondria are surrounded by a line. (",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(c-f) Knockdown of p62 has no influence on Parkin translocation to mitochondria after 6 h of CCCP treatment (c-e), but completely blocks final clearance after 24 h (c, d, f). (e, f) Relative parkin translocation (e) and mitochondrial clearance (f) after p62 knockdown and CCCP treatment (n = 4). Data represent the mean ± s.d., ***P ≤ 0.0005 compared with control siRNA-transfected cells. Representative images of four independent experiments are shown. Scale bars, 10 μm. Immunostainings of control cells are shown in Supplementary Information, Fig. S5d, e.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(g) Western blot of siRNA-transfected HeLa cells used in c-f demonstrates the efficiency of p62 silencing. β-Actin probing served as a loading control. WT, wild-type.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(b) Pathogenic Parkin mutants fail to poly-ubiquitylate endogenous VDAC1 in response to CCCP treatment. HeLa cells were transfected with empty vector (-), Flag-Parkin wild-type or pathogenic mutants along with 6×His-tagged ubiquitin wild-type for 24 h. Cells were treated with CCCP for 6 h and subsequently protein lysates were prepared in urea buffer. Denaturing conditions of Ni-NTA affinity purifications were used to specifically pulldown only proteins covalently modified with 6xHis-tagged ubiquitin. Western blots of protein lysates and purified Ni-NTA agarose elutions were probed with anti-VDAC1, anti-TOM20 and anti-Parkin antibodies. Modification of VDAC1 was observed in cells expressing Parkin wild-type and the functional mutant G328E, whereas non-functional mutants did not have this effect. (",
    "ncbi_link": "ubiquitin: 7316///6233///7311
Parkin: 5071"
  },
  {
    "caption": "(c) In response to CCCP treatment, Parkin catalyses predominantly K27-linked poly-ubiquitin chains on endogenous VDAC1 and is itself strongly poly-ubiquitylated. HeLa cells were transfected with an empty vector (-) or Flag-Parkin wild-type along with 6×His-tagged ubiquitin variants for 24 h. Treatment of cells, preparation of lysates and Ni-NTA purification were performed as described in c and probed for Parkin, VDAC1 and β-actin. WT, wild-type; Ub, ubiquitin.",
    "ncbi_link": "ubiquitin: 7311///7316///6233"
  },
  {
    "caption": "(c) Pathogenic Parkin mutations fail to poly-ubiquitylate endogenous VDAC1 in response to CCCP treatment. Western blot analysis of a time-course experiment with inducible Parkin SH-SY5Y cells after CCCP treatment. Total lysates were prepared, and western blots were probed with specific anti-Parkin and anti-VDAC1 antibodies. β-Actin probing served as a loading control in a-c. WT, wild-type; Ub, ubiquitin.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "VDAC1-specific siRNA abrogates Parkin translocation to mitochondria after 2 h, and mitochondrial clearance after 24 h, of CCCP treatment. Both effects can be rescued by re-transfection with wild-type VDAC1. (a) Immunofluorescence and (b) western blot of siRNA-transfected HeLa cells used in c-g demonstrate partial silencing of endogenous VDAC1. (a) Silenced cells were stained with anti-HtrA2/Omi, a mitochondrial marker (pseudo coloured; blue), and anti-VDAC1 (red) antibodies. (b) Lysates from silenced cells were subjected to western blot analysis and probed with an anti-VDAC1 antibody, while TOM20 and β-actin probing served as loading controls.",
    "ncbi_link": "VDAC1: 7416"
  },
  {
    "caption": "(c-e) Control siRNA- or VDAC1 siRNA-silenced HeLa cells were transfected with the indicated combinations of EGFP-Parkin wild-type, VDAC1-Flag wild-type or appropriate empty vector controls. Cells were treated with CCCP for 2 h and 24 h and stained with anti-HtrA2/Omi (pseudo coloured; blue) and anti-Flag (red) to visualize mitochondrial morphology and re-transfected VDAC1, respectively. Wild-type Parkin was visualized by EGFP epifluorescence (green). Parkin-positive cells are surrounded by a line. Representative pictures of three independent experiments are shown. Scale bars, 10 μm.",
    "ncbi_link": "VDAC1: 7416"
  },
  {
    "caption": "(C) FCS measures the in vivo mobility of exomer components in the cytoplasm. FCS analysis was performed on the GFP, Chs5-GFP and GFP-tagged ChAPs in the wild-type background (top) and on GFP-tagged ChAPs in the Δchs5 background (bottom). 10-20 FCS measurements were performed for each condition using different cells. The ACF of free GFP is fitted with a one-component anomalous diffusion model. The ACF of Chs5 in WT and ChAPs in WT and Δchs5 background is fitted with a two-component diffusion model. Representative ACF curves (thin full lines) and fits (thick dashed lines) are shown. Estimated diffusion correlation times, diffusion coefficients and fractions are shown in Table 1.(D) Quantification of the Chs5 independent fraction of ChAPs present in the cytoplasm based on the measurements shown in (C).(E) Comparison of the residuals of the one-component and two-component fit (arrows).",
    "ncbi_link": "chs5: 851041"
  },
  {
    "caption": "(A) Chs5 is necessary for recruitment and stable binding of ChAPs at the TGN. Differential centrifugation of cell lysates obtained from Chs6-GFP WT and Δchs5 strain. TCL, total cell lysate; S10, 10,000 g supernatant; P10, 10,000 g pellet; S100, 100,000 g supernatant; P100, 100,000 g pellet. Anp1 serves as the Golgi marker and Pgk1 as the cytoplasm marker. A representative immunoblot of three independent biological experiments is shown.",
    "ncbi_link": "chs5: 851041
Chs5: 851041"
  },
  {
    "caption": "(F) Binding kinetics of Chs5-GFP at the TGN in WT, ChAP and strains. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2. The schematic cartoons depict the predicted majority of the analyzed complexes. The violet ovals represent Chs5 dimer and circles represent ChAPs: green:Bch1, red:Bud7, dark blue:Bch2, light blue:Chs6.",
    "ncbi_link": "Bch1: 855277
Bch2: 853898
Bud7: 854475
Chs6: 853346"
  },
  {
    "caption": "(A-B) Overexpression of Bch2 in absence of other ChAPs results in more efficient Chs5 recruitment and stabilization at the TGN. Fluorescence images of cells expressing Chs5-GFP (A) and binding kinetics of Chs5-GFP at the TGN (B) in WT, BCH2 and GPD-BCH2 strains. Bar, 5 µm. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2. The schematic cartoons depict the predicted majority of the analyzed complexes; Chs5 dimer:violet ovals, Bch2:dark blue circles.",
    "ncbi_link": "BCH2: 853898
Bch2: 853898"
  },
  {
    "caption": "(C-D) Overexpression of Chs6 in absence of other ChAPs results in more efficient Chs5 recruitment and stabilization at the TGN. (C) Fluorescence images of cells expressing Chs5-GFP in WT, CHS6 and GPD-CHS6 strains. Bar, 5 µm. (D) Binding kinetics of Chs5-GFP at the TGN in WT, , CHS6 and GPD-CHS6 strains. Data processing was carried out as in (A-B). The schematic cartoons depict the predicted majority of the analyzed complexes; Chs5 dimer: violet ovals, Chs6: light blue circles.",
    "ncbi_link": "Chs6: 853346
CHS6: 853346"
  },
  {
    "caption": "(E-G) Overexpression of Chs6 rescues Chs3 export in absence of other ChAPs. (E) Fluorescence images of cells expressing Chs3-GFP in WT, CHS6 and GPD-CHS6 strains. Arrows point to Chs3-GFP signals at the bud neck. Bar, 5 µm. The inset represents a twofold magnification.(F) Quantification of phenotypes in (E); 100 small budded and 100 large budded cells were quantified per experiment. Average and SD of three independent biological experiments is shown.",
    "ncbi_link": "CHS6: 853346
Chs6: 853346"
  },
  {
    "caption": "(G) Chs3 GFP GPD-CHS6 strain was sensitive to calcofluor to a similar extent as the WT strain. Plates were incubated at 30°C for 2-3 days. A representative drop test of three independent biological experiments is shown.",
    "ncbi_link": "Chs3: 852311
CHS6: 853346"
  },
  {
    "caption": "Fluorescence images of cells expressing Chs5-GFP and TGN marker Sec7DsRed (A) and binding kinetics of Chs5-GFP at the TGN (B) in WT, CHS6 and CHS6BUD7 (A, B) The brightness and contrast were adjusted differently in the merged images. Bar, 5 µm. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2.",
    "ncbi_link": "BUD7: 854475
CHS6: 853346"
  },
  {
    "caption": "Fluorescence images of cells expressing Chs5-GFP and TGN marker Sec7DsRed (C) and binding kinetics of Chs5-GFP at the TGN (D) in WT, or CHS6BCH2 (C, D) strains. The brightness and contrast were adjusted differently in the merged images. Bar, 5 µm. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2.",
    "ncbi_link": "BCH2: 853898
CHS6: 853346"
  },
  {
    "caption": "(A-B) Overexpression of Bch1 displaces Chs6 from the TGN and impairs plasma membrane localization of Chs6-dependent cargo Chs3. Fluorescence images of Chs6-GFP (A) and Chs3-GFP (B) in WT and GPD-BCH1 strains. Bar, 5 µm. Arrows point to Chs3-GFP signals at the bud neck. The inset represents a twofold magnification.",
    "ncbi_link": "BCH1: 855277
Bch1: 855277"
  },
  {
    "caption": "(D) Chitin production is reduced upon Bch1 overexpression. Fluorescence images of chitin stained with calcofluor in Chs3-GFP WT, chs5 and GPD-BCH1 strains.",
    "ncbi_link": "Bch1: 855277
BCH1: 855277
chs5: 851041"
  },
  {
    "caption": "(E) Overexpression of Bch1 does not impair plasma membrane localization of the Bch1-dependent cargo Pin2. Fluorescence images of Pin2-GFP in WT and GPD-BCH1 strains.",
    "ncbi_link": "Bch1: 855277
BCH1: 855277"
  },
  {
    "caption": "(F-I) Overexpression of Chs6 displaces Bch1 and Chs5 from the TGN. Fluorescence images (F-G) and binding kinetics at the TGN (H-I) of cells expressing Bch1-GFP (F, H) and Chs5-GFP (G, I) upon overexpression of Chs6 under GPD promoter from 2μ plasmid. The insets in (F, G) represent two-fold magnifications. The arrows in (F) point to residual Bch1 staining at the TGN. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2. Size bars represent 5 µm.",
    "ncbi_link": "Chs6: 853346"
  },
  {
    "caption": "(A) Overexpression of Pin2 enhances Chs5 stabilization at the TGN. Binding kinetics of Chs5 GFP in WT, bud7bch1 and bud7bch1 strain expressing Bch2-dependent cargo Pin2 from a centromeric or a 2μ plasmid. The mean of 20-30 FRAP measurements from different cells is shown. Calculated parameters are shown in Table 2.",
    "ncbi_link": "bch1: 855277
bud7: 854475
Pin2: 854271"
  },
  {
    "caption": "(B) Comparison of the expression levels of the endogenous Pin2 with the levels of Pin2 expressed from a centromeric or a 2μ plasmid. Pgk1 serves as loading control. A representative immunoblot of three independent biological experiments is shown.",
    "ncbi_link": "Pin2: 854271"
  },
  {
    "caption": "(D) MDMs were infected with ICP0-deficient or revertant HSV-1 (KOS), MOI 3. Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP0: "
  },
  {
    "caption": "(E) THP1-derived cells deficient for cGAS or STING were infected with the shown strains of HSV-1 (MOI 3) or stimulated with poly(I:C) (2 µg/ml). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "cGAS: 115004
STING: 340061"
  },
  {
    "caption": "(A) THP1 cells were infected with HSV-1 KOS or an ICP27-deficient mutant (ΔICP27) on KOS genetic background (MOI 3). Supernatants were harvested from untreated cultures or cells infected for 12 or 18 hours for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(B) MDMs were infected with HSV-1 KOS or ΔICP27 (MOI 3). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(C) THP1-derived cells deficient for cGAS or STING were infected with HSV-1 KOS or ΔICP27 (MOI 3). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "cGAS: 115004
STING: 340061
ICP27: 24271474"
  },
  {
    "caption": "(D) HEK293T cells were transfected with 12 ng STING plasmid DNA, 5 or 25 ng ICP27 plasmid DNA, and reporter gene constructs as indicated (2x104 cells per well). Reporter gene activity was measured in lysates isolated 24 h post transfection.",
    "ncbi_link": "STING: 340061
ICP27: 24271474"
  },
  {
    "caption": "(E) THP1 cells were infected with HSV-1 KOS or ΔICP27 (MOI 3) in the presence or absence of acyclovir (ACV). Supernatants were isolated 18 hpi for measurement of type I IFN bioactivity",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(A) THP1 cells were infected with HSV-1 KOS or ΔICP27 (MOI 3). Cytoplasmic and nuclear extracts were isolated at the indicated time points post infection, and levels of ICP27, RCC1, and GAPDH were determined by Western blotting.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(B) THP1 cells were infected with HSV-1 KOS or ΔICP27 (MOI 10). The cells were fixed at the indicated time points post infection, and stained with DAPI and an antibody against ICP27, and visualized by confocal microscopy. Scale bar 10 μm.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(C, D) THP1 cells were infected with HSV-1 KOS, ΔICP27 or HSV-1 ΔNLS. The localization of the major NLS is illustrated in panel C. Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(E, F) THP1 cells were infected with HSV-1 KOS or ΔICP27 (MOI 3). Cytoplasmic (E) and nuclear extracts (F) were isolated at the indicated time points post infection. Western blotting was used to determine levels of phospho- and total TBK1 were determined in the cytoplasmic fractions and levels of phospho-IRF3 and RCC1 in the nuclear fractions.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "(G-I) HEK293T cells were (G) transfected with STING, TBK1, IRF3-5D, and ICP27, together with the reporter gene constructs indicated. Reporter gene activity was measured 24 h post transfection.",
    "ncbi_link": "IRF3: 3661
TBK1: 29110
STING: 340061
ICP27: 24271474"
  },
  {
    "caption": "(G-I) HEK293T cells were ((H) transfected with STING and stimulated for 16 h with cGAMP (4 μg/ml) together with the reporter gene constructs indicated. Reporter gene activity was measured 24 h post transfection.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(G-I) HEK293T cells were (I) transfected with TRIF, MAVS, STING, and ICP27, together with the reporter gene constructs indicated. Reporter gene activity was measured 24 h post transfection.",
    "ncbi_link": "MAVS: 57506
TRIF: 148022
STING: 340061
ICP27: 24271474"
  },
  {
    "caption": "(D) TBK1 was immunoprecipitated from whole cell lysates from HEK293T cells transfected with ICP27 and each of the adaptor proteins TRIF, MAVS, and STING. The precipitates were immunoblotted for TBK1, ICP27, and STING.",
    "ncbi_link": "MAVS: 57506
TRIF: 148022
STING: 340061"
  },
  {
    "caption": "(E) THP1 control and STING KO cells were infected with HSV-1 KOS (MOI 10) for 6 and 8 h and total lysates were generated. TBK1 was immunoprecipitated, and subjected to Western blotting using antibodies against ICP27, phospho-TBK1 (pTBK1), and TBK1.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(F) THP1 control and TBK1 KO cells were infected with HSV-1 KOS (MOI 10) for 8 h and total lysates were generated. STING was immunoprecipitated, and subjected to Western blotting using antibodies against ICP27 and STING.",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(I) TBK1 was immunoprecipitated from whole cell lysates from HEK293T cells transfected with ICP27 and STING (either WT or S366A). The precipitates were immunoblotted for TBK1, ICP27, and STING.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(C) THP1 cells were infected with HSV-1 (KOS), HSV-2 (HG52), HSV-1 ΔICP27, or HSV-1 ΔICP27 rescued with HSV-2 ICP27 (MOI 3). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP27: 24271474
ICP27: 1487343"
  },
  {
    "caption": "(D) RAW264.7 cells were infected with HSV-1 (KOS), PRV (vBecker3) and the corresponding mutants lacking ICP27 (UL54 in the case of PRV). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity.",
    "ncbi_link": "ICP27: 24271474
UL54: 2952533"
  },
  {
    "caption": "(F) THP1 cells were infected with HSV-1 (KOS), ΔRGG, or ΔICP27 (MOI 3). Supernatants were harvested 18 hpi for measurement of type I IFN bioactivity. ICP27 expression in the infected cells was determined by Western blotting.",
    "ncbi_link": "ICP27: 24271474"
  },
  {
    "caption": "F, qPCR of RAD51 expression measured in NS, BT308 diff, and astrocytes at the indicated time-points after IR (5 Gy, fold vs. non-irradiated cells, ctrl). Data are represented as mean ± SEM.",
    "ncbi_link": "RAD51: 5888"
  },
  {
    "caption": "B, qPCR of SOX2 expression measured in NS 6 h after IR (5 Gy, fold vs. non-irradiated cells, ctrl). *: t-test, p<0.02.",
    "ncbi_link": "SOX2: 6657"
  },
  {
    "caption": "G, qPCR of RAD51 expression in METhigh and METneg subpopulations sorted from BT308NS 24 h after IR (5 Gy, fold vs. non-irradiated control cells, ctrl). *: t-test, P=0.02. Data are represented as mean ± SEM.",
    "ncbi_link": "RAD51: 5888"
  },
  {
    "caption": "B. Genotype distribution in litters from heterozygous matings (Fbxl4+/- x Fbxl4+/-) at embryonic stage 13.5 (E13.5) and of live animals at weaning. Data is presented as a percentage. Embryos n=79, weaned mice n=339. Dashed lines indicate the expected Mendelian ratios. Chi2 test vs expected Mendelian ratios; ***, p<0.001.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "C. Representative images of wild-type (+/+), heterozygous knockout (+/-) and homozygous Fbxl4 knockout embryos (-/-) at E13.5.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "D. Relative levels of mtDNA of Fbxl4 knockout (-/-) embryos and the corresponding wild type (+/+) embryos at E13.5. Data represent mean ± SEM, n=5. Student's t-test; *, p<0.05.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "E. Representative images of male Fbxl4 knockout (-/-) and matched wild-type (+/+) animals at one year of age (left). A hunch-back phenotype was observed both in male and female knockout animals (right, indicated by arrow).",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "A. Relative levels of mtDNA in tissues of 1-year-old Fbxl4 knockout mice determined by quantitative real-time PCR (normalized to controls). Data are presented as mean ± SEM, n=6 for controls and n=8 for knockout animals. Student's t-test; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "B. Transcript levels in indicated tissues of 1-year-old Fbxl4 knockout mice determined by quantitative real-time PCR. Relative mRNA levels in control animals were set as 1 (dashed line). Data are presented as mean ± SEM, n=6 for controls and n=8 for knockout animals. Student's t-test; *, p<0.05; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "C. Western blot analysis of protein steady-state levels in liver protein extracts from wild type (Fbxl4+/+) and Fbxl4 knock-out (Fbxl4-/-) animals. D. Quantification of the western blot in (C). Signal normalized to the average of controls and presented as mean ± SEM, n=4 for both controls and knockout animals. Student's t-test; **, p<0.01; ***, p<0,001.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "E. Quantitative TMT-based proteomic analysis of wild-type and Fbxl4 knock-out liver tissue protein extracts. Proteins from three control and three Fbxl4 knock-out liver protein extracts were TMT-labelled, quantified and analyzed separately as described in Materials and Methods; the data from control and knock-out animals were averaged after the analysis and presented as -log10 of the adjusted p-value vs log2-fold change (logFC). Mitochondrial proteins were selected according to mouse MitoCarta 2.0(Calvo et al, 2016) and highlighted in red; lysosomal proteins were selected according to hLGDB database(Brozzi et al, 2013) and highlighted in yellow.",
    "ncbi_link": "Fbxl4: 269514"
  },
  {
    "caption": "B. Relative mtDNA content in fibroblasts from patients and controls as determined by qRT-PCR using an ND6 probe and normalized to nuclear genomic DNA content using an 18S probe. Individual values are presented for each sample, as well as their mean ± SEM values.",
    "ncbi_link": "18S: 
ND6: 4541"
  },
  {
    "caption": "C. Steady-state protein levels in three control and three FBXL4 patient-derived fibroblasts analyzed by western blotting.",
    "ncbi_link": "FBXL4: 269514"
  },
  {
    "caption": "D. Quantification of the western blot in (C). Signals from the control and FBXL4-mutated cells were considered as biological replicates, normalized to the average of controls and displayed as mean ± SEM (n=3 for each). Student's t-test; *, p<0.05; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "FBXL4: 269514"
  },
  {
    "caption": "B. Steady-state protein levels in wild-type (WT) and FBXL4 knockout (KO) RKO cells.",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "C. (Upper panel) Pulse-chase labeling of mitochondrial translation products in wild type (WT) and FBXL4 knockout (KO) cells. The cells were incubated for 1 hour with a 35S methionine-cysteine labeling mix in the presence of anisomycin to inhibit cytosolic translation (pulse). After removal of the medium, the cells were incubated in complete growth medium without inhibitors and labeled amino acids for 16 or 24 hours (chase). A representative experiment of 4 biological replicates is shown. A Coomassie-stained part of the gel is shown as loading control. (Lower panel) Quantification of the MTCO1-ND4 signal presented as mean ± SEM; n=4 biological replicates; Student's t-test; *, p<0.05.",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "D. (Upper panel) Mitochondrial translation products were labeled in wild type (WT) and FBXL4 knock-out (KO) RKO cells for 60 minutes as in C, followed by 24 h chase in the presence of 5 μM epoxomicin (epoxo) or 20 mM ammonium chloride (NH4Cl). A representative experiment of n≥3 biological replicates is shown. A fragment of the Coomassie-stained gel is shown as loading control. (Lower panel) Quantification of the ND4-MTCO1 signal. n≥3 biological replicates, data are presented as mean ± SEM. Student's t-test; *, p<0.05.",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "E-F. Steady-state levels of indicated proteins in wild type and FBXL4 knockout RKO cells treated with NH4Cl",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "E-F. Steady-state levels of indicated proteins in wild type and FBXL4 knockout RKO cells treated with epoxomicin (Epoxo, F).",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "A. Confocal images from the mito-QC-expressing fibroblast lines. Scale bar 25 μm. B. Quantification of the mitolysosomes/cell area (μm2) using the mito-QC counter plugin for ImageJ (Montava-Garriga et al, 2020). At least 3 technical replicates for each line and n>15 cells analyzed for each technical replicate. Data is presented as 25 to 75 percentile box with the indicated median and whiskers representing 5-95 percentile interval. Non-parametric Mann-Whitney test; ***, p<0.001.",
    "ncbi_link": "mito-QC: "
  },
  {
    "caption": "A. Western blot analysis of mTORC1 activity in C2C12-Vevtor (VC) and Aster-C KO (KO) cells in complete medium (CM) and in response to nutrient starvation or stimulation with amino acids for 30 min. B and C. Statistical analysis of phosphorylated level of S6K (B) and 4E-BP1 (C) in C2C12-Vector and Aster-C KO cells in CM, under nutrient starvation (-AA) and in response to stimulation with amino acids (+AA) using ImageJ software. Data are represented as mean ± SD (n=3 biological replicates). *p < 0.05, **p<0.01 by Student's t test.",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "D. Immunostaining of endogenous mTOR and LAMP1 in C2C12-Vector and Aster-C KO cells under nutrient starvation (-AA) and in response to AA stimulation (+AA). LAMP1 was immunostained as a lysosome marker. Arrows highlight the co-localization of mTOR with LAMP1. Scale bar, 40 μm (Row 1) and 10 μm (Rows 2, 3, 4).",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "F. Western blot analysis of mTORC1 activity in Aster-C KO cells stably re-expressing exogenous GFP-Aster-C under nutrient starvation and AA stimulation. Aster-C KO cells were transfected with GFP-Aster-C and selected with G418 for 2 weeks.",
    "ncbi_link": "GFP: 
Aster-C: 207798"
  },
  {
    "caption": "G. Immunostaining of endogenous mTOR and LAMP1 in C2C12-Vector and Aster-C KO cells under cholesterol depletion by treatment with 0.5% MCD for 2 hrs (-CHOL) or cholesterol (50 µM) re-stimulation for 1 hr (+CHOL). Arrows highlight the co-localization of mTOR with LAMP1. Scale bar, 40 μm (Row 1) and 10 μm (Rows 2, 3, 4).",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "H. Western blot analysis of mTORC1 activity in C2C12-Vector and Aster-C KO cells in CM, under starvation, cholesterol depletion by treatment with 0.5% MCD for 2 hrs or cholesterol (50 µM) re-stimulation for the indicated time.",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "A. Confocal image analysis depicting the co-localization of Aster-C with the ER in C2C12 cells transiently expressing GFP-Aster-C and DsRed-ER under starvation and in response to AA stimulation. Scale bar, 5 μm.",
    "ncbi_link": "DsRed: 
GFP: 
ER: 811
Aster-C: 207798"
  },
  {
    "caption": "B. Subcellular fractionation analysis of mTOR, GATOR2 complex and Aster-C localization in HEK293T cells transiently expressing FLAG-Aster-C under starvation and in response to AA stimulation. LAMP1, Sec63 and GAPDH were used as lysosomal (Lyso), rough ER (RER) and cytosol (Cyto) protein markers, respectively. Microsomal fraction (Micro) was also used in the blot.",
    "ncbi_link": "FLAG: 
Aster-C: 207798"
  },
  {
    "caption": "C. Subcellular fractionation analysis of mTOR and GATOR2 complex in C2C12-Vector and Aster-C KO cells under starvation and in response to AA stimulation. LAMP1, Sec63 and GAPDH were used as lysosomal (Lyso), rough ER (RER) and cytosol (Cyto) protein markers, respectively.",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "B. Co-IP analysis of the interaction of COPA with mTOR in HEK293T cells transiently expressing GFP-COPA in response to starvation and AA stimulation. Anti-GFP antibody was used for immunoprecipitation. Black arrow indicates the COPG protein.",
    "ncbi_link": "GFP: 
COPA: 1314"
  },
  {
    "caption": "C. Co-IP analysis of the interaction of COPA with mTOR in C2C12-Vector and Aster-C KO cells in response to starvation and AA stimulation. Anti-COPA antibody was used for immunoprecipitation.",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "D. Confocal imaging analysis depicting the co-localization of YFP-mTOR (yellow) with GFP-COPA (green) and lysosomes (red) in live C2C12-Vector and Aster-C KO cells in response to nutrient starvation and re-stimulation by AA. Arrows highlight co-localization of mTOR, COPA and lysosomes. Scale bar, 20 μm. E and F. Statistical analysis of the Pearson's correlation coefficient of mTOR/Lysosome (E) and COPA/Lysosome (F) in Figure 3D (n=10-12 cells per group). Data are represented as mean ± SD. ***p<0.001 by one-way ANOVA.",
    "ncbi_link": "Aster-C: 207798"
  },
  {
    "caption": "A. Confocal imaging analysis depicting the lysosomal association of mTOR in response to AA stimulation in the presence or absence of BFA (10 μM) or Exo-2 (10 μM) in live C2C12 cells transiently expressing YFP-mTOR and stained with Lysotracker Red. Scale bar, 20 μm.",
    "ncbi_link": "YFP: 
mTOR: 2475"
  },
  {
    "caption": "D. Western blot analysis of mTORC1 activity in C2C12-Vector and ARF1 KO cells in CM, in response to nutrient starvation and AA stimulation.",
    "ncbi_link": "ARF1: 11840"
  },
  {
    "caption": "E. Confocal imaging analysis depicting COPA puncta (green) formation and co-localization with lysosomes (red) in live C2C12 cells transiently expressing GFP-COPA and stained with Lysotracker Red in response to nutrient starvation and AA stimulation in the presence or absence of BFA (10 μM) or Exo-2 (10 μM). Arrows highlight co-localization of COPA with lysosomes. Scale bar, 5 μm.",
    "ncbi_link": "GFP: 
COPA: 1314"
  },
  {
    "caption": "B. Western blot analysis of mTORC1 activity in wild type (WT) and MYH10 KO MEF cells cultured in CM, or in response to starvation and AA stimulation.",
    "ncbi_link": "MYH10: 77579"
  },
  {
    "caption": "C. Western blot analysis of mTORC1 activity in MYH10 KO MEF cells with stably re-expressed exogenous mCherry-MYH10 in response to starvation and AA stimulation. MYH10 KO MEF cells were transfected with mCherry-MYH10 and selected with G418 for 2 weeks.",
    "ncbi_link": "mCherry: 
MYH10: 77579
MYH10: 4628"
  },
  {
    "caption": "D. Confocal imaging analysis depicting COPA puncta (green) formation and co-localization with mTOR (red) in live C2C12 cells transiently expression GFP-COPA and YFP-mTOR in response to nutrient starvation in the presence or absence of BBS (10 µM). Arrows highlight the co-localization of mTOR with COPA. Scale bar, 20 μm.",
    "ncbi_link": "GFP: 
YFP: 
COPA: 1314
mTOR: 2475"
  },
  {
    "caption": "A. Confocal imaging analysis depicting mTOR puncta (green) formation on actin filaments (red) in COS-7 cells transiently expressing YFP-mTOR in response to AA stimulation in the presence or absence of latrunculin B (LA-B, 100 nM). Actin filaments were stained using BODIPY™ 558/568-Phalloidin. Arrows indicated the association of mTOR with actin filaments. Scale bar, 5 μm.",
    "ncbi_link": "YFP: 
mTOR: 2475"
  },
  {
    "caption": "D. Co-IP analysis of the interaction of Aster-C with COPA and MYH10 in the presence or absence of LA-B (100 nM) or cytochalasin D (Cyto-D, 250 nM) in HEK293T cells transiently expressing FLAG-Aster-C. Anti-FLAG antibody was used for immunoprecipitation.",
    "ncbi_link": "FLAG: 
Aster-C: 207798"
  },
  {
    "caption": "(A) CP20 and OVCAR4 cells were transfected with either non-target miRNA control (miR-CTL), miR-15a, or miR-195. 72h following transfection, cells were lysed and immunoblotted for detection of MICU1, BMI1, BCL2, and MFN2. GAPDH and VDAC were used as loading control.",
    "ncbi_link": "miR-15a: 406948
miR-195: 406971"
  },
  {
    "caption": "(B) miR-195 expression in FTE188 and ovarian cell lines as determined by RT-qPCR normalized with U6. Data are mean ± S.D., n=3 (Biological repeats). *P<0.05, Student's t-test.",
    "ncbi_link": "U6: 
miR-195: 406971"
  },
  {
    "caption": "(D) Anti-miR-195 was transfected in the FTE188 cell line, level of miR-195 was measured using RT-qPCR (left) and MICU1 levels were measured using immunoblotting (right). Data are mean ± S.D., n=3 (Biological repeats). *P<0.05, Student's t-test.",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "(A, B) CP20, OVCAR4, and OVSAHO cells were transfected with non-target micro RNA control (miR-CTL) or miR-195, 24 h post-transfection, cells were recounted and plated as single cells for anchorage-dependent (A) or anchorage-independent (B) clonal growth. After 10 (CP20) or 14 (OVCAR4 and OVSAHO) days, colonies were quantified using an Optronix GelCount colony counter. The left panel shows representative images of the colonies and the right panel depicts a graphical representation of data presented as percent clonal growth relative to the control (miR-CTL).",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "(C) Migration of miR-CTL, miR-195, and miR-195+ MICU1 (pLYS1-MICU1-Flag) transfected cells, towards serum gradient was examined and the number of cells per field was counted. The left panel shows representative images and the right panel depicts a graphical representation of relative migration compared to the control (miR-CTL).",
    "ncbi_link": "Flag: 
MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "(D) Invasion of miR-CTL, miR-195, and miR-195 + MICU1 cells through fibronectin-coated filters was examined using Boyden chamber and number of cells per field was counted. Left panel shows representative images and the right panel depicts a graphical representation of relative invasion compared to the control (miR-CTL).",
    "ncbi_link": "MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "(B) MICU1 3'UTR in LightSwitch™ 3′UTR Reporter Vector (wild type or miR-195 binding site deleted) was co-transfected with either non- target miR control (miR-CTL) or different concentrations of miR-195. Post 24h transfection luciferase (Renilla) activity was measured. Relative light units (RLU) compared to miR-CTL were plotted. Data are mean ± S.D. n=3 (Biological repeats). *P<0.05, Student's t-test.",
    "ncbi_link": "luciferase: 
MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "CP20 cells were transfected as indicated, 48 h post transfection 4x106 cells were permeabilized, and extra-mitochondrial calcium ([Ca2+]out) clearance was measured, representative traces of [Ca2+]out‑ clearance in miR-CTL and miR-195 transfected cells. [Ca2+]out pulses and FCCP were delivered as indicated.",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "CP20 cells were transfected as indicated, 48 h post transfection 4x106 cells were permeabilized, and extra-mitochondrial calcium ([Ca2+]out) clearance was measured, representative traces of [Ca2+]out‑ clearance in control siRNA (siCTL) and siMICU1 transfected cells. [Ca2+]out pulses and FCCP were delivered as indicated.",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "(E) Bar graph illustrating the number of Ca2+ pulses handled by control miR, miR-195, siCTL and siMICU1 transfected cells. Mean ±SEM; n=3-4 (Biological repeats). *P<0.05, Student's t-test.",
    "ncbi_link": "MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "(F) Representative [Ca2+](m) traces after addition of FCCP (10 µM) in permeabilized CP20 cells transfected with non-target miR-CTL or miR-195. (G) Quantification of resting matrix [Ca2+](m) after addition of FCCP. n=5 (Biological repeats) *P<0.05, Student's t-test, ",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "(H) Representative traces of mitochondrial membrane potential (∆Ψμ) in CP20 cells transfected with miR-CTL or miR-195. (I) Quantification of relative ∆Ψμ. (n=5, Biological repeats). ",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "(J) Intracellular lactate was measured in miR-CTL, miR-195, siCTL, and siMICU1 expressing OVCAR4, CP20, and OVSAHO cells. n=3, biological repeats *P<0.05, Student's t-test.",
    "ncbi_link": "MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "(K&L) miR-CTL, miR-195, or miR-195 + pLYS1-MICU1-Flag transfected cells were stained with MitoSOX Red, and mitochondrial ROS levels were determined by flow cytometry. The histogram shows representative staining and bar graph (right) shows results of three independent experiments. Mean ± SEM; . n=3, biological repeats. *P<0.05 when comparing with miR-CTL, # P<0.05 when comparing with miR-195 by Student's t-test.",
    "ncbi_link": "Flag: 
MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "(A&B) Stable cell lines for CP20 and OVCAR4 expressing GFP-miR-195 or non-target miR-GFP were generated using lentiviral mediated transduction and were selected using puromycin; representative images are shown. Scale bars, 50 µm.",
    "ncbi_link": "GFP: 
miR-195: 406971"
  },
  {
    "caption": "(C) Relative miR-195 expression was measured using RT-qPCR in stable cell lines, normalized with U6. Mean ± SEM; n=3, Biological repeats. *P<0.05, Student's t-test.",
    "ncbi_link": "U6: 
miR-195: 406971"
  },
  {
    "caption": "(D) CP20 and OVCAR4 stable cell lines were transfected as either empty vector (EV) or pLYS1-MICU1-Flag (MICU1) and relative MICU1 levels were evaluated using immunoblotting.",
    "ncbi_link": "Flag: 
MICU1: 10367"
  },
  {
    "caption": "(E, F) CP20 and OVCAR4 stable cell lines transfected as in (D) were counted and re-plated for anchorage-dependent (E) and independent clonal growth (F). Quantification compared to the miR-CTL stable cells transfected with EV is shown. Mean ± SD; n=3, Biological repeats. *P<0.05 when comparing with miR-CTL, # P<0.05 when comparing with miR-195 by Student's t-test.",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "(A) Female athymic mice were injected subcutaneously with either CP20 GFP-miR-CTL or CP20- GFP-miR-195 cells. Mice injected with the miR-195 expressing cells (miR-195) had significantly smaller tumor volumes than control mice (miR-CTL). Data are mean ± S.D, n=10. *P<0.05, Student's t-test.",
    "ncbi_link": "GFP: 
miR-195: 406971"
  },
  {
    "caption": "(B) Tumor doubling time was significantly longer in the mice injected with miR-195 expressing cells than in control mice. Data are mean ± S.D, n=10. *P<0.05, Student's t-test.",
    "ncbi_link": "miR-195: 406971"
  },
  {
    "caption": "Representative histology images of tumors from mice xenografts of CP20-GPF-miR-CTL (miR-CTL) or CP20-GPF-miR-195 (miR-195) cells with Ki67 expression (Scale Bar = 50 μm) (E), CD31 positive vessels (Scale Bar = 100 μm) and TUNEL staining (Scale Bar = 50 μm)",
    "ncbi_link": "GPF: 
miR-195: 406971"
  },
  {
    "caption": "Representative histology images of tumors from mice xenografts of CP20-GPF-miR-CTL (miR-CTL) or CP20-GPF-miR-195 (miR-195) cells with Ki67 expression (Scale Bar = 50 μm) (F) graph showing quantification of each marker in tumors from the experimental mice; values are mean ±SD, n=10, *P<0.05, Student's t-test.",
    "ncbi_link": "GPF: 
miR-195: 406971"
  },
  {
    "caption": "(G) Female athymic mice were injected subcutaneously with either CP20 GFP-miR-CTL or CP20- GFP-miR-195 or CP20- GFP-miR-195 + MICU1 cells and tumor volume was measured, values are mean ±SE, n=10. *P<0.05, Student's t-test.",
    "ncbi_link": "GFP: 
MICU1: 10367
miR-195: 406971"
  },
  {
    "caption": "Somatic mutations distribution: SNVs and InDels displayed by each metastasis (listed in the Y axis) were detected by Strelka2 tool (Kim et al., 2018). Brown traits represent single mutations. The number of fully shared (red), partially shared (orange) or private (yellow) mutations is indicated in the horizontal bar below. Five cancer-associated genes (TP53, ARID2, NTRK1, SMARCA4 and ZFHX3) mutated in all metastases are highlighted.",
    "ncbi_link": "ARID2: 196528
NTRK1: 4914
SMARCA4: 6597
TP53: 7157
ZFHX3: 463"
  },
  {
    "caption": "A) Infection susceptibility (top) to VSVG and Spike-typed lentiviruses of a panel of lung cancer cell lines with or without (Empty vector) overexpression of ACE2. ACE2 protein levels were determined by Western-blot (bottom).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "C) Gene-level scores obtained by robust ranking algorithm analysis of the sgRNA relative abundances between cells infected with Spike-typed lentiviruses and uninfected cells. Genes were ordered alphabetically in the x-axis and the top hits (log10(enrichment-score) < -5) were colored and labelled. Note that CTSL and CTSL1 are different gene isoforms.",
    "ncbi_link": "CTSL: 1514
CTSL1: 1514"
  },
  {
    "caption": "B) Susceptibility to infection with Spike-typed and VSVG-typed lentiviruses in Calu1ACE2 CRISPR KO cell lines with loss-of-function of selected screen candidates. NT596 and NT764 are two non-targeting CRISPR controls. ACE2 are Calu1ACE2 cells transduced with a CRISPR vector against ACE2. Bars represent the average and standard error of the mean (SEM) of the percentage of infected cells in each condition (three biological replicates), normalized to the non-targeting control cell line NT596. The t-test p-value between the relative percentage of infection with Spike-typed and VSVG-typed for each cell line is indicated.",
    "ncbi_link": "CRISPR: 
ACE2: 59272"
  },
  {
    "caption": "C) Confocal microscopy images of SPNS1-KO1 and PLAC8-KO1 Calu1ACE2 cells overexpressing CRISPR-resistant SPNS1- or GFP-PLAC8, respectively.",
    "ncbi_link": "CRISPR: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "D) Rescue experiments in PLAC8 and SPNS1 Calu1ACE2 KO cell lines: bar plot showing the average (three biological replicates) and SEM percentage of infection (normalized to NT596 with GFP overexpression) of Spike-typed and VSVG-typed lentiviruses in PLAC8-KO1 and SPNS1-KO1 cell lines that overexpress CRISPR-resistant PLAC8- or GFP-SPNS1 constructs. The significance above each bar represents the t-test p-value between each condition and the control cell line (NT596 with GFP overexpression)",
    "ncbi_link": "GFP: 
CRISPR: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "A, B) Susceptibility to infection with SARS-CoV-2 viruses in Calu1ACE2 (A) and H1299ACE2 (B) cell lines with loss-of-function of the indicated genes. Left: representative immunofluorescence images of SARS-CoV-2 nucleocapsid protein (green) and cell nuclei (red) in the indicated cell lines. Scale bar: 20 µm. Right: immunofluorescence quantification of the number of infected cells at 24 h post-infection in the different loss-of-function cell lines infected with SARS-CoV-2. Bars represent the average and SEM of the percentage of infected cells relative to CRISPR non-targeting transduced (NT596) cells in three biological replicates (three different CRISPR KO cell lines infected independently). The significance above each bar represents the one-tail t-test p-value between each condition and CRISPR non-targeting transduced (NT596) cells.",
    "ncbi_link": "CRISPR: 
ACE2: 59272"
  },
  {
    "caption": "C) Western-blot analyses of SPNS1 and PLAC8 protein levels in the different lung cancer cell lines tested in Fig 1 with or without ACE2 overexpression. Note that PLAC8 and SPNS1 immunodetection was performed on the same blots than in Figure 1A, and that ACE2 and Actin panels from Figure 1A were included here to allow comparison.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "D) Susceptibility to Spike-typed lentiviruses in the indicated ACE2 overexpressing cancer cell lines that were transduced with GFP, GFP-PLAC8 or GFP-SPNS1. Bars represent the average and SEM of the percentage of infected cells in three technical replicates (independent infections of the same cell line) relative to Calu1ACE2-GFP cells. The significance above each bar represents the t-test between GFP-PLAC8 or GFP-SPNS1 and GFP cells for each cell line.",
    "ncbi_link": "GFP: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "E) Susceptibility to infection with SARS-CoV-2 viruses in cell lines that overexpress ACE2 and GFP-SPNS1 or GFP-PLAC8. Bars represent the immunofluorescence quantification of the number of SARS-CoV-2 infected cells at 24 h post-infection. Representative images of SARS-CoV-2 nucleocapsid immunofluorescence (green) and cell nuclei (red) in GFP and GFP-PLAC8 cells are shown right to each plot.",
    "ncbi_link": "GFP: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "A) Binding and endocytosis studies with Alexa Fluor 647-conjugated S-RBD or transferrin in Calu1-ACE2-RFP cells deficient in PLAC8 and SPNS1. Left: scatterplots of flow cytometry data showing the cutoffs used to define ACE2-RFP and Alexa Fluor 647 positive cells. Right: bar plots showing the ratio of cells positive for Alexa Fluor 647 in either ACE2-RFP positive (red) or negative (blue) cells in binding and endocytosis experiments with S-RBD or transferrin. Bars represent the average and SEM of three biological replicates (three different CRISPR KO cell lines). The significance above each bar represents the t-test p-value between each condition and CRISPR non-targeting transduced (NT596) cells.",
    "ncbi_link": "CRISPR: 
RFP: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "B-E) Endocytosis experiments with S-RBD in PLAC8- or SPNS1-KO Calu1-ACE2-RFP cells with overexpression of GFP-PLAC8 or GFP-SPNS1, respectively. Cells were incubated with S-RBD for 1 h at 37 ºC and fixed with 4% p-formaldehyde after an acid wash to remove non-internalized S-RBD. Representative wide-field fluorescence images (B) and quantification of mean fluorescence intensities of each fluorophore (C) in each cell show that S-RBD signal correlates with ACE2-RFP expression but not with GFP-PLAC8 or GFP-SPNS1. The Pearson correlation coefficient (r) and correlation test p-value (p) is indicated within each scatterplot. Each dot represents a cell measurement from different microphotographs of a single replicate. Scale bar: 20 µm. Representative fluorescence confocal microphotographs (D) and spot colocalization analyses using ComDet plugin (E) demonstrate colocalization of S-RBD endosomes with ACE2-RFP and GFP-PLAC8 or GFP-SPNS1. (D) Red ovals defining the detected S-RBD dots are overlaid in each channel to assess the colocalization with ACE2-RFP, GFP-PLAC8 or GFP-SPNS1. Inlets show a magnification of the region defined by the white squares. Scale bar: 20 µm. (E) Boxplots representing the percentage of internalized S-RBD that colocalize with ACE2-RFP, GFP-PLAC8, GFP-SPNS1 or their combination (ACE2-RFP and GFP-PLAC8 or ACE2-RFP and GFP-SPNS1). The central band represents the median, the box represents the interquartile range (IQR) between the 25th and 75th percentile, and the whiskers extend from the box to 1.5*IQR. Each dot represents a cell measurement from different microphotographs of a single replicate.",
    "ncbi_link": "GFP: 
RFP: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "C) Representative images (left) and quantification (right) of the number of acidic particles in PLAC8- and SPNS1-KO Calu1ACE2 cells compared to CRISPR non-targeting control cells (NT596) using live-cell lysotracker staining. The two samples Wilcoxon Test p-value of the pooled observations compared to NT596 cells is indicated above each condition. The central band represents the median, the box represents the interquartile range (IQR) between the 25th and 75th percentile, and the whiskers extend from the box to 1.5*IQR. Each dot represents a cell measurement from different microphotographs of a single replicate. Three biological replicates per condition were used.",
    "ncbi_link": "CRISPR: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "D) Lysosomal degradation studies in Calu1ACE2 cells using the fluorogenic substrate DQ-Red-BSA. Left: density plots representing the shift in fluorescence intensity in NT596 cells untreated or treated with DQ-Red-BSA under growth or serum starvation conditions. Right: bar plot representing the mean and SEM of the median fluorescence intensity values (MFI) of three biological replicates of PLAC8- and SPNS1-KO and CRISPR non-targeting cells in growth and serum starvation conditions.",
    "ncbi_link": "CRISPR: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "E) Representative images (left) and quantification (right) of the number of LC3B particles in PLAC8- and SPNS1-KO Calu1ACE2 cells compared to CRISPR non-targeting control cells (NT596) using LC3B immunofluorescence staining. The two samples Wilcoxon Test p-value of the pooled observations compared to NT596 cells is indicated above each condition. The central band represents the median, the box represents the interquartile range (IQR) between the 25th and 75th percentile, and the whiskers extend from the box to 1.5*IQR. Each dot represents a cell measurement from different microphotographs of a single replicate. Three biological replicates per condition were used.",
    "ncbi_link": "CRISPR: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "F) Autophagic flux analyses using the fluorescence reporter GFP-LC3-RFP-LC3ΔG in PLAC8- and SPNS1-KO Calu1ACE2 cells compared to CRISPR non-targeting control cells (NT596). Left: density plots showing the shift in GFP intensity under starvation conditions compared to control growth conditions in NT596 Calu1ACE2 cells. Right: bar plots showing the mean and SEM of the median GFP/RFP intensity ratio of three biological replicates in the different cell lines and conditions.",
    "ncbi_link": "CRISPR: 
GFP: 
RFP: 
ACE2: 59272
PLAC8: 51316
SPNS1: 83985"
  },
  {
    "caption": "(C) H1299 cells stably expressing GFP-LC3 were incubated for 2 h in EBSS, and expression of various BCL‐2 homologues was analysed by western blot. Alternatively, primary cortical neurons were incubated for 4 h in media without glucose/pyruvate.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(D) H1299 cells stably expressing GFP-LC3 were incubated for 3 h in media without glucose/pyruvate, followed by re‐addition of glucose and pyruvate for the indicated times.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(E) HeLa cells were infected with 5 p.f.u. per cell of either Ad HA‐tBID or Ad LacZ for 7 h, the media being changed to EBSS for the last 3 h where indicated. Alternatively, cells were treated with 50 μM camptothecin for 3 h.",
    "ncbi_link": "BID: 637"
  },
  {
    "caption": "(A) H1299 cells stably expressing GFP-LC3 were incubated for the indicated times in EBSS in the presence of 50 μM zVAD‐FMK and analysed by immunofluorescence for cyt c or active BAX (6A7 epitope). As a positive control, cells were infected with 5 p.f.u. per cell Ad HA‐tBID for 7 h. Data are expressed as the average of three experiments±s.d.",
    "ncbi_link": "BID: 637
LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) H1299 cells stably expressing GFP-LC3 were incubated for 4 h in either EBSS or media without glucose/pyruvate. Cells were then fixed, stained with an antibody against cyt c and analysed by immunofluorescence. Scale bars=50 μm.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "( Alternatively (C), the cells were analysed by western blot for the presence of MCL‐1 and the autophagic markers GFP-LC3 (anti‐GFP antibody) and p62.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(D) H1299 cells stably expressing GFP-LC3 were incubated for the indicated times in either EBSS or media without glucose/pyruvate and analysed by western blot for the presence of MCL‐1 and autophagic markers.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(E, F) H1299 cells stably expressing GFP-LC3 were pre‐incubated for 1 h with 5 mM 3MA (E) or 200 nM bafilomycin (F), and then incubated for 2 h in complete media or EBSS in the presence of 3MA or bafilomycin. Lysates were then analysed for the presence of MCL‐1, the autophagy marker p62 and actin as a loading control.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) H1299 cells stably expressing GFP-LC3 were infected with 10 p.f.u. per cell of either Ad LacZ or Ad Myc‐MCL‐1 for 24 h then incubated in EBSS for 4 h. Alternatively, cells were transfected with control or MCL‐1 siRNA 24 h before EBSS treatment. Cells were stained with an antibody against cyt c and analysed by immunofluorescence. Representative images are shown. Scale bars=50 μm.",
    "ncbi_link": "Ad LacZ: 
LC3: 440738///81631///84557
MCL‐1: 4170"
  },
  {
    "caption": "(C, D) H1299 cells stably expressing GFP-LC3 were transfected as in A and incubated with 200 nM bafilomycin for 1 h where indicated. The levels of endogenous LC3‐II relative to actin were quantified by western blot in C. Data are expressed as the average of three experiments±s.d, *P0.05.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(E, F) H1299 cells stably expressing GFP-LC3 were treated as in A and analysed by western blot for the presence of p62 and GFP-LC3.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(G) Primary cortical neurons of the indicated genotypes were infected with a lentivirus expressing Cre at the time of plating and analysed for the presence of MCL‐1 and p62 by western blot 3 days later.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "(H) Transformed wild‐type (WT) and MCL‐1Δ/Δ (KO) MEFs were analysed by western blot for the expression of endogenous LC3.",
    "ncbi_link": "MCL‐1: 17210"
  },
  {
    "caption": "(I, J) Colocalization of GFP-LC3 vesicles with the lysosomal marker LAMP1 was analysed by immunofluorescence in cells treated as in A. The number of LC3‐positive vesicles that colocalised with LAMP1 was quantified in I. Data are expressed as the percentage of LC3 vesicles per cell that are LAMP1‐positive±s.e.m., with at least 14 cells per condition. Representative images are shown in J. Arrows indicate LC3‐positive vesicles colocalizing with LAMP1. Scale bars=10 μm.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(A) MCL‐1 interacts with Beclin‐1. Lysates from H1299 stably expressing GFP-LC3 were immunoprecipitated using control or MCL‐1‐specific antibodies and analysed for the presence of Beclin‐1 by western blot.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) H1299 cells stably expressing GFP-LC3 were fractionated into HM (containing mitochondria), and LM (containing ER). Fractions were analysed for the presence of MCL‐1, BCL‐2, Beclin‐1, the mitochondrial marker mtHSP70 and the ER marker calreticulin.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) Control and MCL‐1Δ/Δ mice.",
    "ncbi_link": "MCL‐1: 17210"
  },
  {
    "caption": "(C) Brain morphology of MCL‐1Δ/Δ. Brain sections were stained with cresyl violet and imaged using a × 1 objective.",
    "ncbi_link": "MCL‐1: 17210"
  },
  {
    "caption": "(D-G) Cortical neurons around the lesion in MCL‐1Δ/Δ animals are positive for the autophagic marker LC3. Brain sections from animals with the indicated genotypes (P14 for E, G; P7 for H) were stained for LC3 (Green) and the neuronal marker NeuN (in H, red), along with the nuclear stain Hoechst (Blue). Confocal images were taken using × 10 (E) or × 63 (G, H) objectives. Scale bars=200 μm (E); 50 μm (G, H). Quantification of the LC3 staining is shown in D. The total number of cells was determined by counting the Hoechst‐positive nuclei. Data are expressed as percent of LC3‐positive cells in at least three animals per genotype±s.d. *P0.01. (F) Quantification of the total surface area occupied by autophagosomes. Data are expressed as percent of total cortical area covered by autophagosomes in at least 16 EM images per genotype±s.d. P0.005 (I) Representative EM images from MCL‐1+/Δ and MCL‐1Δ/ΔP14mice. N, nucleus; *, autophagosomal structures; arrowheads, double membrane; arrow, mitochondrion inside a vesicle.",
    "ncbi_link": "LC3: 67443///66734
MCL‐1: 17210"
  },
  {
    "caption": "(B) Active BAX (6A7) and active caspase‐3 were also quantified by staining the cortex of 1‐ to 14‐day‐old MCL‐1Δ/Δ mice. Representative images from at least three sections from each animal were counted. The total number of cells was determined by counting the Hoechst‐positive nuclei. Data are expressed as percent of positive cells for at least three animals per genotype±s.d. *P0.05.",
    "ncbi_link": "MCL‐1: 17210"
  },
  {
    "caption": "(C) Active BAX is present in a subset of LC3‐positive cells. Sections from P7 and P14 MCL‐1Δ/Δ brains were stained for LC3 (Green) and active BAX (6A7; Red). Confocal images were taken using × 63 objective. Arrows point to BAX‐positive, LC3‐negative cells. Representative images are shown. Scale bars=50 μm.",
    "ncbi_link": "MCL‐1: 17210"
  },
  {
    "caption": "Primary cortical neurons of the indicated genotypes were infected with a lentivirus expressing Cre at the time of plating and analysed for the presence of the caspase‐cleaved fragment of the caspase‐3 substrate CAS5 days later. Alternatively (E), the neurons were analysed for cytochrome c release by immunofluorescence. Data are expressed as percent of positive cells for at least three embryos per genotype±s.d.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "(A) Brains from E12.5 Foxg1 Cre MCL‐1 animals were analysed by western blot for the presence of the caspase‐cleaved fragment of the caspase‐3 substrate p130CAS and the autophagic markers LC3 and p62.",
    "ncbi_link": "Cre: 
Foxg1: 15228
MCL‐1: 17210"
  },
  {
    "caption": "(B) Autophagy in Foxg1 Cre MCL‐1Δ/Δ mice. Brain sections from E15.5 animals with the indicated genotypes were stained for LC3 (green). Confocal images were taken using × 20 (bottom panel) or × 63 (top and middle panels) objectives. Scale bars=50 μm.",
    "ncbi_link": "Cre: 
Foxg1: 15228
MCL‐1: 17210"
  },
  {
    "caption": "(A) Brain morphology of P14 MCL‐1Δ/Δ Beclin‐1+/− mice. Brain sections were stained with cresyl violet and imaged using a × 1 objective.",
    "ncbi_link": "Beclin‐1: 56208
MCL‐1: 17210"
  },
  {
    "caption": "(B-D) Active BAX (6A7; B) and active caspase‐3 (C) were quantified by staining the cortex of 14‐day‐old MCL‐1Δ/Δ and MCL‐1Δ/Δ Beclin-1+/− mice. The number of BAX‐positive LC3‐negative cells was also quantified. (D)Representative images from at least three sections from each animal were counted. The total number of cells was determined by counting the Hoechst‐positive nuclei. Data are expressed as percent of positive cells for least three animals per genotype±s.d. *P0.05.",
    "ncbi_link": "Beclin-1: 56208
MCL‐1: 17210"
  },
  {
    "caption": "(E) Survival data from MCL‐1Δ/Δ (n=14) and their MCL‐1Δ/Δ Beclin‐1+/− littermates (n=13).",
    "ncbi_link": "Beclin‐1: 56208
MCL‐1: 17210"
  },
  {
    "caption": "RT-PCR validations of regulated IR-transcripts through splicing upon bicuculline stimulation (C) Expression of the IR-isoforms and the spliced isoforms were analyzed by semi-quantitative PCR (left panels). Means and SDs (standard deviations) of PIR values are shown beneath each panel. In addition, fold changes in the expression of the IR-transcripts (red and orange) and spliced (dark grey) isoforms were assessed with real-time qPCR using three different primer sets, as represented in the top scheme. Note that the Gria3 spliced transcript (C) does not correspond to the canonical mRNAs and presumably arise from a first step of recursive splicing and thereby likely require splicing completion to generate fully mature Gria3 transcripts (Sibley et al, 2015).",
    "ncbi_link": "Gria3: 53623"
  },
  {
    "caption": "Brightfield microscopy of 2.5 dpc embryos obtained from crosses of Nsmce2GT/+ mice. The right panel is of the same 2 embryos shown on the left panel, 36 h after being cultured in vitro. The arrow indicates embryos that showed asymmetric cell sizes when isolated, which degenerated upon culture. These embryos were identified as Nsmce2GT/GT through genotyping.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Examples of the type of nuclei found on Nsmce2GT/GT and Nsmce2+ (+/+ or +/GT) 2.5 dpc embryos, 12 h after in vitro culture. Mutant embryos were identified due to the absence of NSMCE2 signal (green). DAPI was used to stain DNA (blue). White arrows indicate examples of cells with condensed chromosomes or irregular shapes, which are hardly seen in wild type embryos.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Immunoprecipitation of SMC5 (and IgG, as a control) from a 48‐h culture of B lymphocytes of wt and Nsmce2SD/SD animals. NSMCE2 and SMC6 levels on the immunoprecipitates were analyzed by WB. The image of the Ponceau staining is shown as a loading control.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "IF of NSMCE2 foci in MMS‐treated Nsmce2+/+ and Nsmce2SD/SD MEFs. Scale bar, 2.5 μm.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Representative picture of 6‐month‐old Nsmce2+/+ and Nsmce2SD/SD littermates.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Kaplan-Meyer survival curves of Nsmce2+/+ and Nsmce2SD/SD mice. The P‐value was calculated with the Mantel-Cox long‐rank test.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "A Kaplan-Meyer survival curves of Nsmce2+/+ and Nsmce2+/GT mice. The P‐value was calculated with the Mantel-Cox long‐rank test. ***P 0.001.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "B Tumor incidence found on Nsmce2+/+ and Nsmce2+/GT mice at the time of death (i.e. moribund mice).",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "C NSMCE2 levels evaluated by Western blot in 2 independent pairs of Nsmce2+/+ and Nsmce2+/GT MEFs. β‐actin was used as a loading control. Numbers shown bellow indicate the relative amounts of NSMCE2 in each sample.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "D Sister chromatid exchange (SCE) events found per metaphase on Nsmce2+/+ and Nsmce2+/GT MEFs. ***P 0.001.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "E, F Relative percentages of micronuclei (E) and polynucleated cells (F) on cultures of Nsmce2+/+ and Nsmce2+/GT MEFs. Data are representative of three independent experiments. Error bars indicate SD. ***P 0.001.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "NSMCE2 levels assessed by WB in UQ.CreERT2 transgenic Nsmce2+/+ and Nsmce2lox/lox littermate MEFs, 24 h after exposure to 4‐OHT. Tubulin levels are shown as a loading control.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "Clonogenic assay on immortalized UQ.CreERT2/Nsmce2lox/lox MEFs. The picture shows the colonies detected after 10 days of growth in the presence or absence of 4‐OHT, upon staining with crystal violet.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "NSMCE2 and BRCA1 foci in MMS‐treated (1 mM for 1 h; 24‐h recovery) UQ.CreERT2/Nsmce2lox/lox MEFs, 48 h after being treated (or not) with 4‐OHT. Scale bar, 5 μm.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "SCE events per metaphase on UQ.CreERT2/Nsmce2lox/lox MEFs grown in the presence of 4‐OHT for 72 h. ***P 0.001.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "Example of SCE events (arrows) found on Nsmce2‐deleted MEFs.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "SCE events at telomeres on UQ.CreERT2/Nsmce2lox/lox MEFs grown in the presence of 4‐OHT for 72 h, as detected by CO‐FISH (see ). Data are representative of three independent experiments. Error bars indicate SD. *P 0.05.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "Telomere lengths of UQ.CreERT2 Nsmce2lox/lox MEFs treated or not with 4‐OHT for 72 h.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "Percentage of cells with micronuclei found on cultures of UQ.CreERT2/Nsmce2lox/lox MEFs treated or not with 4‐OHT for 72 h. Data are representative of three independent experiments. Error bars indicate SD. ***P 0.001.",
    "ncbi_link": "Cre: 
Nsmce2: 68501"
  },
  {
    "caption": "Intrauterine dwarfism observed upon NSMCE2 deletion on 17.5 dpc embryos. Pregnant females were treated at 14.5 dpc for 3 days with intraperitoneal injections of 4‐OHT. The image represents the difference in size observed between Nsmce2+/+ and Nsmce2lox/lox embryos carrying the UQ.CreERT2 transgene (Nsmce2+/+ and Nsmce2lox/lox, from now on).",
    "ncbi_link": "Cre: 
Nsmce2: 68501
NSMCE2: 68501"
  },
  {
    "caption": "Representative picture of Nsmce2+/+ and Nsmce2lox/lox animals fed for 40 weeks with a 4‐OHT‐containing diet (see also Movies EV1 and EV2).",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Images illustrating the presence of altered pigmentation problems that arise on Nsmce2lox/lox mice.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Percentage of fat against total body mass on Nsmce2+/+ and Nsmce2lox/lox animals. ***P 0.001.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "White bloodcell counts (WBC) from Nsmce2+/+ and Nsmce2lox/lox animals. ***P 0.001.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Percentage of γH2AX‐positive micronuclei found on the intestinal epithelia of Nsmce2+/+ and Nsmce2lox/lox animals (see Appendix Fig S11). Data are representative of three independent experiments. Error bars indicate SD. *P 0.05.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "A WB illustrating the depletion of NSMCE2 in B cells isolated from 2‐month‐old CD19+/Cre animals of the indicated genotypes, 48 h after being stimulated in vitro with lipopolysaccharide (LPS). Tubulin was used as a loading control.",
    "ncbi_link": "Cre: 
CD19: 12478"
  },
  {
    "caption": "B Representative FACS analysis from the B‐cell cultures mentioned in (A). DNA content was measured with propidium iodide (PI). Note the presence of cells with > 4n DNA content in NSMCE2‐deleted cells.",
    "ncbi_link": "NSMCE2: 68501"
  },
  {
    "caption": "C, D Frequency of origin firing (C) and fork rate (D) were analyzed by DNA fiber analyses (see ) from fibers prepared from B‐cell cultures explained in (A). No significant differences were observed between Nsmce2+/+ and Nsmce2lox/loxB cells. Data are representative of two independent experiments. Error bars indicate SD. Between 200 and 300 tracks were measured to estimate fork rate and 300-500 for the calculation of origin firing frequencies.",
    "ncbi_link": "Nsmce2: 68501"
  },
  {
    "caption": "Representative pictures of the spleens from 2‐month‐old CD19+/Cre animals of the indicated genotypes.",
    "ncbi_link": "Cre: 
CD19: 12478"
  },
  {
    "caption": "Numbers of B and T cells from 2‐month‐old CD19+/Cre animals of the indicated genotypes evaluated by flow cytometry (B220: B‐cell marker; CD3: T‐cell marker).",
    "ncbi_link": "Cre: 
CD19: 12478"
  },
  {
    "caption": "SCE events per metaphase on B cells obtained from CD19+/Cre animals of the indicated genotypes, 72 h after being stimulated in vitro with LPS. **P 0.01, ***P 0.001.",
    "ncbi_link": "CD19: 12478"
  },
  {
    "caption": "Analysis of forward (FSC) and side (SSC) scatter parameters of B cells obtained from CD19+/Cre animals of the indicated genotypes, 48 h after being stimulated in vitro with LPS. The emergence of bigger cells is noticeable on cells lacking both BLM and NSMCE2.",
    "ncbi_link": "BLM: 12144
CD19: 12478
NSMCE2: 68501"
  },
  {
    "caption": "Examples of the types of nuclei found on Blm and Nsmce2 double‐mutant B cells (compared with wild‐type B cells), in cells obtained from (E). DAPI was used to stain DNA. Whereas wt nuclei are regular in size, double‐mutant cells invariably presented enlarged, multilobulated, and irregular nuclei. Scale bar, 2.5 μm.",
    "ncbi_link": "Blm: 12144
Nsmce2: 68501"
  },
  {
    "caption": "A, B (A) Confocal imaging of FOS DNA FISH with concurrent SPT5 and Pol II-S5P IF showing that SPT5 and Pol II-S5P occupied the FOS loci after serum starvation. Zoomed-in views of the merged regions are indicated by the white arrow. (B) Same as Fig 1A. but for FOS DNA FISH with concurrent SPT5 and NELFE IF.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "G-I ChIP-qPCR showing that the occupancies of Pol II (G), SPT5 (H), and NELFE (I) at the promoters and gene bodies of HSP70, GAPDH, and MYC in HeLa cells. The HEMO gene serves as a negative control for ChIP-qPCR. Error bars represent standard error of means. Results are plotted with four technical repeats from two biological replicates. Two-tailed, unpaired Student's t test was performed. For Pol II ChIP, HSP70_promoter, **p = 0.0014; GAPDH_promoter, p = 0.8385; GAPDH_gene body, ***p < 0.0001; MYC_promoter, p = 0.1765; MYC_gene body, ***p = 0.0002. For SPT5 ChIP, HSP70_promoter, **p = 0.0033; GAPDH_promoter, p = 0.9603; GAPDH_gene body, **p = 0.0012; MYC_promoter, p = 0.9898; MYC_gene body, ***p < 0.0001. For NELFE ChIP, HSP70_promoter, p = 0.3913; GAPDH_promoter, p = 0.9347; MYC_promoter, p = 0.8558.",
    "ncbi_link": "HEMO: 100288413
GAPDH: 2597
HSP70: 3303
MYC: 4609"
  },
  {
    "caption": "A Western blot analysis of re-expression of mCherry-SPT5, mCherry-SPT5ΔNTR or mCherry-SPT5ΔCTR after SPT5 depletion. α-Tubulin was used as a loading control. Results are representative of two biological replicates.",
    "ncbi_link": "mCherry: 
SPT5: 6829"
  },
  {
    "caption": "B Confocal imaging of nascent RNA labeled by EU in HEK-293T cells expressing SPT5, SPT5ΔNTR or SPT5ΔCTR after SPT5 depletion.",
    "ncbi_link": "SPT5: 6829"
  },
  {
    "caption": "G, H ChIP-qPCR showing the occupancies of Pol II at the promoters and gene bodies of GAPDH (G), and MYC (H) in HEK-293T cells expressing SPT5, SPT5ΔNTR or SPT5ΔCTR after SPT5 depletion. The HEMO gene serves as a negative control for ChIP-qPCR. Error bars represent standard error of means. Results are plotted with four technical repeats from two biological replicates. Two-tailed, unpaired Student's t test was performed. *p < 0.05, **p < 0.01, ***p < 0.001, n.s.=not significant. For GAPDH_promoter, p value (from left to right, < 0.0001, < 0.0001, < 0.0001, 0.0044, 0.8873, 0.9310, 0.6855, 0.9615); GAPDH_gene body, p value (from left to right, 0.0370, 0.0214, 0.0574, 0.0256, 0.9536, 0.8038, 0.7623, 0.8773); For MYC_promoter, p value (from left to right, 0.0002, 0.0014, 0.0004, 0.0048, 0.0670, 0.7501, 0.3482, 0.3284); MYC_gene body, p value (from left to right, 0.0004, 0.0013, 0.0081, 0.0299, 0.1332, 0.5839, 0.4404, 0.6170).",
    "ncbi_link": "HEMO: 100288413
GAPDH: 2597
MYC: 4609
SPT5: 6829"
  },
  {
    "caption": "C Confocal imaging of FOS RNA FISH with concurrent SPT5 IF in wild type (WT) and ENL KO HCT116 cells after serum treatment. Zoomed-in views of the merged regions are indicated by the white arrow.",
    "ncbi_link": "FOS: 2353
ENL: 4298"
  },
  {
    "caption": "H Confocal images showing SPT5 in nuclear puncta in WT or ENL KO cells treatment with KL-1. I Violin plot showing the number of cells containing nuclear puncta in Fig 5H. Results are representative of three biological replicates, each n > 20. Two-tailed, unpaired Student's t test was performed. ***p < 0.001.",
    "ncbi_link": "ENL: 4298"
  },
  {
    "caption": "A Confocal images showing co-localization of AFF4 with SPT5 in nuclear puncta in AFF4 wild type (WT) or R258W cells. B Dotplot (left) showing the AFF4 or SPT5 puncta area in AFF4 WT or R258W cells (Fig 7A). Two-tailed, unpaired Student's t test was performed. AFF4 R258W vs. WT, *p = 0.0254. Violin plot (right) showing the Pearson correlation coefficient of co-localization ratio (Fig 7A). Each n > 20. Results are representative of three biological replicates. Two-tailed, unpaired Student's t test was performed. AFF4 R258W vs. WT, *p = 0.0166. C",
    "ncbi_link": "AFF4: 27125"
  },
  {
    "caption": "K-N ChIP-qPCR showing the occupancies of Pol II (K), AFF4 (L), SPT5 (M), and PAF1 (N) at the promoter and gene body of HSP70 in AFF4 WT and R258W HEK-293T cells after heat shock for 2 hours. The HEMO gene serves as a negative control for ChIP-qPCR. Error bars represent standard error of means. Results are plotted with four technical repeats from two biological replicates. Two-tailed, unpaired Student's t test was performed. For Pol II ChIP, HSP70_promoter, ***p < 0.0001; HSP70_gene body, ***p = 0.0002. For AFF4 ChIP, HSP70_promoter, ***p < 0.0001; HSP70_gene body, ***p < 0.0001. For SPT5 ChIP, HSP70_promoter, ***p < 0.0001; HSP70_gene body, **p = 0.0086. For PAF1 ChIP, HSP70_promoter, ***p = 0.0007; HSP70_gene body, **p = 0.0021. ",
    "ncbi_link": "AFF4: 27125
HEMO: 100288413
HSP70: 3303"
  },
  {
    "caption": "A. Schematic representation of the experimental protocol. Abbreviations: LCM, laser capture microdissection. B, C. RT-PCR performed on RNA extracted from axons collected by LCM (Ax) or from eyes. (B) β-Actin mRNA is present both in eyes and axons, while MAP2 and H4 are present only in the eye sample, suggesting the absence of contamination from cell bodies or other cells in LCM axonal samples (Bellon et al, 2017). Abbreviations: Ax, axonal sample; Eye, stage 37/38 eye; LCM, laser capture microdissection; -, PCR no template control; NT, RT no template control. ",
    "ncbi_link": "β-Actin: 108703086///398459
H4: 378643
MAP2: 108701430///379931"
  },
  {
    "caption": "H. Quantification of the expression levels of pre-mir-181a-1 using the 2-ΔCt method and U6 as normalizer from small total RNA fraction (<~150 nt). Each data point corresponds to one independent experiment. n=3 independent experiments. Values are mean ± SEM. Abbreviations: ns, not significant.",
    "ncbi_link": "pre-mir-181a-1: 
U6: "
  },
  {
    "caption": "I. Total number of MB puncta normalized to axon length (µm). Each data point corresponds to one axon. Total number of puncta and axons analyzed: 928 puncta, 61 axons (WT), 226 puncta, 15 axons (co-MO), 208 puncta, 35 axons (MO). n=4 independent experiments. Values are mean ± SEM. Abbreviations: ns, not significant; co-MO, control morpholino; pri-miR-MO, morpholino blocking pre-miR-181a-1 processing by targeting the Drosha cleavage site.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "M. Frequency (in percentage) of puncta colocalization between MB and cy5-pre-miR-181a-1 (#MB+/pre-miR+). Each data point corresponds to one axon. Total number of puncta and axons analyzed: 354 puncta, 32 axons (MB), 337 puncta, 32 axons (cy5-pre-miR-181a-1). n=5 independent experiments. Values are mean ± SEM. Abbreviations: MB, molecular beacon.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "N. Representative image of RGC axons. White, red and blue arrows indicate, respectively, co-localized, single MB, and single pre-miR-181a-1 puncta. Scale bars: 5µm.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "D. Frequency distribution (in percentage) of MB (endo) and cy3-pre-miR-181a-1 (exo) puncta along the RGC axon shaft. Each data point corresponds to one independent experiment. Total number of puncta and axons analyzed: 353 puncta, 20 axons (endo), 484 puncta, 29 axons (exo). n=3 (endo), n=4 (exo) independent experiments. Values are mean ± SEM. Abbreviations: MB, molecular beacon; ns, not significant.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "E. Average velocity of MB (endo) and cy3-pre-miR-181a-1 (exo) puncta. Each data point corresponds to one punctum. Total number of puncta and axons analyzed: 353 puncta, 20 axons (endo), 484 puncta, 29 axons (exo). n=3 (endo), n=4 (exo) independent experiments. Values are median with interquartile range. Abbreviations: MB, molecular beacon; ns, not significant; antero, anterograde movement; retro, retrograde movement.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "F. MSD data for MB (endo) and cy3-pre-miR-181a-1 (exo) tracked particles were fitted with an anomalous diffusion model and α thus calculated (red). Total number of particles and axons analyzed: 67 particles, 20 axons (endo), 82 particles, 29 axons (exo). n=3 (endo), n=4 (exo) independent experiment. Values are mean ± SEM. Abbreviations: MB, molecular beacon.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "G. MSD alpha coefficient distribution for each single MB (endo) and cy3-pre-miR-181a-1 (exo) tracked particle. Each data point corresponds to one particle. Total number of particles and axons analyzed: 67 particles, 20 axons (endo), 82 particles, 29 axons (exo). n=3 (endo), n=4 (exo) independent experiments. Values are median with interquartile range.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "H. Relative frequency distribution (percentage) of MB (endo) and cy3-pre-miR-181a-1 (exo) tracked particles. Each data point corresponds to one independent experiment. Total number of particles and axons analyzed: 67 particles, 20 axons (endo), 82 particles, 29 axons (exo). n=3 (endo), n=4 (exo) independent experiments. Values are mean ± SEM. Abbreviations: MB, molecular beacon; ns, not significant.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "B. Representative axon where MB-labeled pre-miR-181a-1 (red) and CD63-eGFP-labeled vesicles (green) are co-trafficked (white arrows). Abbreviations: MB, molecular beacon. Scale bars: 5µm.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "E. Representative time-lapse depicting MB-labeled pre-miR-181a-1 (red arrow) and CD63-eGFP-positive vesicle (green arrow) co-trafficked along the axon shaft to the growth cone (delineated with dashed white lines) wrist (white arrowhead) and central domain (white star). Scale bars: 5µm.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "F. Frequency (in percentage) of MB-labeled pre-miR-181a-1 co-trafficked with CD63-eGFP-positive vesicles. Each data point corresponds to one axon. Total number of puncta and axons analyzed: 253 puncta, 22 axons (MB+), 306 puncta, 22 axons (CD63+). n=5 independent experiments. Values are mean ± SEM. Abbreviations: CD63, CD63-eGFP; MB, molecular beacon.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "G. Frequency distribution (in percentage) of MB-labeled pre-miR-181a-1 co-trafficked with CD63-eGFP-positive vesicles. Each data point corresponds to one axon. Total number of puncta and axons analyzed: 92 puncta, 22 axons (anterograde), 78 puncta, 22 axons (retrograde). n=5 independent experiments. Values are mean ± SEM. Abbreviations: CD63, CD63-eGFP; MB, molecular beacon.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "E. Representative images of co-electroporated axons. Dashed white lines delineate axons. White arrows indicate colocalized puncta. Colored arrows represent non-colocalized signal as follows: cyan for pre-miR-181a-1 and yellow for Lamp1 or Rab5a. Abbreviations: Lamp1, Lamp1-eGFP; Rab5a, Rab5a-eGFP or Rab5a-mRFP; pre-miR-181a-1, cy3-pre-miR-181a-1 or cy5-pre-miR-181a-1. Scale bars: 5μm.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "F. Frequency (in percentage) of pre-miR-181a-1 colocalization with specific organelle markers. Each data point corresponds to one axon. Total number of puncta, axons and independent experiments analyzed: 825 puncta, 41 axons, n=8 (pre-miR-181a-1/CD63), 732 puncta, 33 axons, n=7 (pre-miR-181a-1/Rab7a), 681 puncta, 29 axons, n=5 (pre-miR-181a-1/LysoTracker), 501 puncta, 17 axons, n=2 (pre-miR-181a-1/Lamp1), 791 puncta, 25 axons, n=3 (pre-miR-181a-1/Rab5a). Values are median with interquartile range. Abbreviations: CD63, CD63-eGFP or CD63-mRFP; Rab7a, Rab7a-eGFP or Rab7a-mRFP, Lamp1, Lamp1-eGFP; Rab5a, Rab5a-eGFP or Rab5a-mRFP; pre-miR-181a-1, cy3-pre-miR-181a-1 or cy5-pre-miR-181a-1.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "G. Representative images of co-electroporated axons. Dashed white lines delineate axons. White arrows indicate colocalized puncta. Colored arrows represent non-colocalized signal as follows: magenta for CD63, cyan for pre-miR-181a-1, yellow for Rab7a and blue for LysoTracker. Abbreviations: CD63, CD63-eGFP or CD63-mRFP; Rab7a, Rab7a-eGFP or Rab7a-mRFP; pre-miR-181a-1, cy3-pre-miR-181a-1 or cy5-pre-miR-181a-1. Scale bar: 5μm.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "H. Frequency (in percentage) of pre-miR-181a-1 colocalization with vesicles double positive for organelle markers. Each data point corresponds to one axon. Total number of puncta, axons and independent experiments analyzed: 745 puncta, 23 axons, n=5 (CD63/pre-miR-181a-1/Rab7a), 577 puncta, 18 axons, n=3 (CD63/pre-miR-181a-1/LysoTracker). Values are median with interquartile range. Abbreviations: ns, not significant; CD63, CD63-eGFP or CD63-mRFP; Rab7a, Rab7a-eGFP or Rab7a-mRFP; pre-miR-181a-1, cy3-pre-miR-181a-1 or cy5-pre-miR-181a-1.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "I. Representative 3D-STED super-resolution image. Total number of puncta, axons and growth cones analyzed: 99 puncta, 16 axons and 10 growth cones (MB), 291 puncta, 36 axons and 15 growth cones (cy3-pre-miR-181a-1). n=2 (MB), n=3 (cy3-pre-miR-181a-1) independent experiments. Abbreviations: CD63, CD63-eGFP; pre-miR-181a-1, cy3-pre-miR-181a-1; MB; molecular beacon.",
    "ncbi_link": "pre-miR-181a-1: "
  },
  {
    "caption": "C. Representative E13.5 mice brain cross-section (dashed red line in the schematic) comprising the optic nerve (ON) stained with anti-neurofilament and anti-HA antibodies to detect RGC axons and (FLAG-HA2)-Dicer, respectively. Note the absence of HA signal in wild type (WT) mice. The white dashed line delineates the ON. Zoom of the triple stained ON (right panel): Dicer signal is detected inside ON cells surrounding axon bundles but not in axons per se (arrowheads). n=3 independent experiments. Abbreviations: WT, wild type; HA, (FLAG-HA2)-Dicer; E13.5, embryonic day 13.5; ONH, optic nerve head; ON, optic nerve. Scale bars: 30µm.",
    "ncbi_link": "FLAG: 
HA: 
Dicer: 192119"
  },
  {
    "caption": "Quantification of miRNA and pre-miRNA expression levels using the 2-ΔCt method and U6 as normalizer, upon Sema3A (B) stimulation. Data are normalized to PBS control. Each data point represents a single RT-qPCR reaction. n=3 (B) independent experiments. Values are mean ± SEM. Abbreviations: ns, not significant.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "Quantification of miRNA and pre-miRNA expression levels using the 2-ΔCt method and U6 as normalizer, upon Slit2 (C) stimulation. Data are normalized to PBS control. Each data point represents a single RT-qPCR reaction. n=4 (C) independent experiments. Values are mean ± SEM. Abbreviations: ns, not significant.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "B. Representative images of RGC axons within the optic tectum. A subset of aberrantly projecting axons are indicated (red arrows). Note that a few straying axons are always observed within the wild type tectum. Abbreviations: co-MO, control morpholino. Scale bars: 20µm. C. Quantification of misprojecting axons. Each data point corresponds to one brain. Total number of brains analyzed: 45 brains (co-MO), 52 brains (miR-181-MO). n=4 independent experiments. Values are mean ± SEM. Abbreviations: co-MO, control morpholino. ",
    "ncbi_link": "miR-181: "
  },
  {
    "caption": "D. Schematic representation of the experimental paradigm. Concentrations used: 0.5μg/μL pCS2-mCherry or pCS2-eGFP plasmids; 250μM miR-181-MO or control MO cocktail; 50μM miR-181 or control mimics (top). Representative images of RGC axons within the optic tectum. White arrows indicate axons targeted both by MO (green) and miRNA mimics (red) (bottom). Abbreviations: co-MO, control morpholino. Scale bars: 20µm. E. Quantification of misprojecting axons. The number reported on the bars are the total number of co-electroporated axons. Note how miR-181 mimics rescued aberrant misprojection of morphant axons in vivo. Each data point corresponds to one independent experiment. Total number of axons and brains analyzed: 96 axons, 4 brains (co-MO+ctrl mimics), 101 axons, 4 brains (miR-181-MO + ctrl mimics), 134 axons, 4 brains (miR-181-MO+miR-181 mimics). n=4 independent experiments. Values are mean ± SEM. Abbreviations: co-MO, control morpholino; ns, not significant. ",
    "ncbi_link": "eGFP: 
mCherry: 
miR-181: "
  },
  {
    "caption": "F. Representative images of RGC axons within the optic tectum. A subset of aberrantly projecting axons are indicated (red arrows). Note that a few straying axons are always observed within the wild type tectum. Abbreviations: co-MO, control morpholino. Scale bars: 20µm. G. Quantification of misprojecting axons. Each data point corresponds to one brain. Total number of brains analyzed: 21 brains (co-MO), 31 brains (miR-181-MO). n=3 independent experiments. Values are mean ± SEM. Abbreviations: co-MO, control morpholino. ",
    "ncbi_link": "miR-181: "
  },
  {
    "caption": "I. Frequency (in percentage) of the amount of time embryos spent on black background. Each data point corresponds to one embryo. Total number of embryos analyzed: 43 embryos (co-MO), 45 embryos (miR-181-MO). n=4 independent experiments. Values are mean ± SEM. Abbreviations: co-MO, control morpholino.",
    "ncbi_link": "miR-181: "
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Concentrations used: 200ng/mL Sema3A; 100µM cycloheximide Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). (B) 200ng/mL Sema3A was bath applied with or without 100µM cycloheximide (CHX, a translational blocker). Mutating TUBB3 3'UTR did not affect fluorescence recovery in basal conditions compared to WT indicating that mature miRNAs do not regulate the constitutive TUBB3 expression in distal axons.",
    "ncbi_link": "Venus: 
TUBB3: 495319"
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Concentrations used: 200ng/mL Sema3A; Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). , isolated axons (C) were used for FRAP analysis.",
    "ncbi_link": "Venus: "
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Concentrations used: 200ng/mL Sema3A; 2µM co-MO or MOs-3p. Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). isolated transfected axons (D) were used for FRAP analysis.",
    "ncbi_link": "Venus: "
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). In vivo (E), whole embryos with exposed brain were used. The electroporated eye was removed prior to mounting the embryo to eliminate somatic contribution. (E) The red area on the brain schematic indicate Sema3A expressing territories. Numbers of axons analyzed are reported between brackets.",
    "ncbi_link": "Venus: "
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Concentrations used: 200ng/mL Sema3A Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). Ex vivo, whole explants were used for FRAP analysis. APP, Amyloid beta precursor protein",
    "ncbi_link": "Venus: 
Amyloid beta precursor protein: 398223
APP: 398223"
  },
  {
    "caption": "Quantification (in percentage) of the axonal fluorescence recovery after photobleaching (FRAP) of different Venus-3'UTR constructs ex vivo and in vivo. Concentrations used: 200ng/mL Sema3A Growth cones expressing Venus alone (no 3'UTR) displayed a minimal amount of recovery after photobleaching corresponding to Venus diffusion from adjacent, non-bleached regions to the bleached growth cone (Wong et al, 2017). Ex vivo, whole explants were used for FRAP analysis. THBS1, Thrombospondin 1",
    "ncbi_link": "Venus: 
THBS1: 779026
Thrombospondin 1: 779026"
  },
  {
    "caption": "H,I. Representative growth cones depicting Venus fluorescence intensity as a heatmap. Dashed white lines delineate the growth cones. Abbreviations: wt, wild type; mut, miR-181-5p responsive elements mutated; CHX, cycloheximide; TUBB3, tubulin beta 3 class III. Scale bars: 10µm.",
    "ncbi_link": "miR-181-5p: "
  },
  {
    "caption": "G. Percentage of collapsed growth cones in axons transfected with co-MO, MOs-3p + co-MO and MOs-3p + MOs-TUBB3. Each data point corresponds to one independent experiment. Total number of growth cones counted: 152 (co-MO), 155 (MOs-3p + coMO), 179 (MOs-3p + MOs-TUBB3). n= 3 independent experiments. Values are mean ± SEM. Abbreviations: ns, not significant; co-MO, control morpholino; TUBB3, tubulin beta 3 class III.",
    "ncbi_link": "TUBB3: 495319
tubulin beta 3 class III: 495319"
  },
  {
    "caption": "Comparable mean SV number per ribbon in wild-type at the distal (Ds., H) and the proximal (Pr., I) part of the ribbon. More SVs are observed at inhibitory OtofPga/Pga ribbons compared to inhibitory wild-type synapses at both ribbon parts, and further at OtofPga/Pga synapses under rest in the Pr. part. Data are presented as mean ± SEM; the red dotted line highlights the wild-type mean SV number per ribbon under rest as a reference point;",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Representative virtual sections of wild-type (J) and OtofPga/Pga (K) ribbon synapses under inhibition. Counted RA-SVs are marked with white asterisks. Magnification, 12,000x; scale bar, 100 nm.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Exemplary virtual sections of wild-type and OtofPga/Pga under inhib (L,M), rest (L',M') and stim (L'',M''). At OtofPga/Pga SVs are densely packed. Blue arrowheads indicate proteinaceous filaments between wild-type SVs. Magnification 12,000x; scale bar, 100 nm.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Depicted are the fractions of SVs without filaments, ribbon-attached SVs (Ri.), interconnected SVs (In.) and SVs with Ri. + In. per ribbon, at (A) the distal (Ds.) and (B) the proximal (Pr.) part of the ribbon. Data are represented as mean ± SEM of wild-type and OtofPga/Pga IHCs under inhib, rest and stim. (A) Upon stimulation, in the Ds. part at wild-type, the fraction of SVs without filaments reduces, but of SVs with Ri. + In. increases significantly. At OtofPga/Pga IHCs the fraction of SVs without filaments is reduced when comparing stim vs. inhib. The fraction of interconnected SVs increases with stimulation compared to inhibition and rest. In the mutant (inhib), the fraction of interconnected SVs decreases compared to wild-type (inhib), and Ri. + In. SVs reduce vs. wild-type (stim). (B) The fraction of SVs without filaments increased at inhibited OtofPga/Pga synapses. The red dotted lines in (A) and (B) represent the mean fraction of RA-SVs/ribbon part of resting wild-type for each defined sub-pool.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "The cumulative probability distribution of RA-SVs plotted against the individual filament length. The graph illustrates shorter filaments in wild-type and OtofPga/Pga ribbon synapses upon stimulation.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Decreased mean filament length upon stimulation in wild-type and OtofPga/Pga ribbon synapses. Resting OtofPga/Pga exhibit the shortest mean filament length. The red dotted lines represent the mean RA-filament length in resting wild-type for each sub-pool.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Depicts the fraction of non-tethered and single-tethered MP-SVs per ribbon. Data are presented in mean ± SEM. The fraction of non-tethered SVs reduces in wild-type and OtofPga/Pga after stimulation and the fraction of single membrane-attached tethers increases in wild-type upon stimulation. In resting wild-type, most single-tethered SVs are attached to the presynaptic density.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Example tomographic virtual sections from inhibitory: wild-type (A) and OtofPga/Pga (B); stimulatory: wild-type (C) and OtofPga/Pga (D). Tethered SVs are highlighted in orange with orange tether(s); single-tethers (with orange arrowhead) and multiple-tethers (with brown arrowhead). The number of tethers per SV is indicated. Magnification: 12,000x; scale bar, 40 nm. Virtual sections from inhibitory: wild-type (E) and OtofPga/Pga (F); stimulatory: wild-type (G) and OtofPga/Pga (H). Docked SVs at the AZ-membrane (blue line) are highlighted (orange asterisk). Some docked SVs are localized close to the presynaptic density (PD, pink outline), anchoring the ribbon (R). Magnification: 12,000x; scale bar, 100 nm.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Percentage of multiple-tethered MP-SVs per ribbon of the total MP-SV pool show more multiple-tethered SVs in OtofPga/Pga IHCs. Percentage of docked MP-SVs per ribbon of the total MP-pool. The number of docked SVs is significantly increased at OtofPga/Pga inhibited and specifically at stimulated AZs. P-values for (I) and (J) are calculated by Fisher's exact Chi-square test, wild-type: inhib, n = 102 SVs; rest, n = 82 SVs; stim, n = 99 SVs; OtofPga/Pga: inhib, n = 123 SVs; rest, n = 96 SVs; stim, n = 111 SVs; ns p > 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Bar-plots show the distance of multiple-tethered (O) and docked (P) SVs from presynaptic density (PD), 0-100 nm: MP-SV pool (dark blue); 100-500 nm: peripheral SV pool (light blue). Upon stimulation, multiple-tethered and docked SVs are localized significantly closer to the PD in OtofPga/Pga. P-values for (O) and (P) are calculated by Wilcoxon Rank test, * p < 0.05, *** p < 0.001, ns p > 0.05 and Ø inconclusive statistics because occurrence of docked SVs in wild-type resting condition is extremely rare. Multiple-tethered SVs, wild-type: inhib, n = 3 SVs; rest, n = 13 SVs; stim, n = 3 SVs; OtofPga/Pga: inhib, n = 21 SVs; rest, n = 34 SVs; stim, n = 16 SVs; docked SVs, wild-type: inhib, n = 2 SVs; rest, n = 1 SVs; stim, n = 7 SVs; OtofPga/Pga: inhib, n = 20 SVs; rest, n = 4 SVs; stim, n = 18 SVs.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "The graph depicts the mean length of single membrane-, presynaptic density-attached and multiple-tethers. Data are presented as mean ± SEM. Stimulated OtofPga/Pga synapses exhibit a shorter average tether length compared to stimulated wild-type.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "Total mean tether length in the MP-SV pool. Data are presented as mean ± SEM. Longer tethers are present upon stimulation in wild-type. Resting OtofPga/Pga ribbon synapses harbor the longest tethers, and tether where shorter at stimulated OtofPga/Pga synapses compared to wild-type. The red dotted lines represent the mean MP tether length in resting wild-type for each sub-pool.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "K, Immunofluorescence staining for H3K79me3 in control and Dot1l KO nuclei. Scale bar, 2µm.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "F, RNA FISH for major satellite transcripts and simultaneous staining for H3K79me3 in control and Dot1l KO mESCs. Scale bar, 5µm. Below left, quantitation of fluorescence intensity along a line bisecting a representative nucleus. Bisecting lines used to generate the plots are shown in the merged images. Below right, quantitation of total FISH fluorescence signal for n=46 cells of each genotype. Line summaries show mean ± standard deviation. ***p<0.0001, unpaired Welch's t-test.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "A, ChIP-qPCR for HP1β at selected repeat elements in Dot1l KO and wild type mESCs. Bars represent mean of n=2 biological replicates. Neg. control indicates an intergenic locus (mm10 chr19:51758385-58758494) not strongly associated with either euchromatin or heterochromatin.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "B, Immunofluorescence staining of HP1β (green) in wild type and Dot1l KO mESCs. DNA is stained with DAPI (blue). Quantification of signal is shown at right. Each point represents one nucleus (Dot1l KO n=83 and control n=104 nuclei). Scale bar, 10µm. ***p<0.0001, Mann-Whitney U test.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "J, H3K79me3 enrichment at major satellite sequences in Smarca5 knockdown (KD) relative to scrambled shRNA control mESCs measured by ChIP-qPCR. Bars represent mean of n=3 biological replicates and error bars represent ± SD. p=0.0876 for the major satellite element (one-sample t-test compared to expected fold change of 1, shown as a dashed line).",
    "ncbi_link": "Smarca5: 93762"
  },
  {
    "caption": "L, Immunofluorescence staining of H3K79me3 (red) in mouse 3T3 fibroblasts transduced with a vector expressing GFP and a short hairpin against Smarca5 (shSmarca5) compared to untransduced control. Arrowheads indicate DAPI-dense chromocenters. Merge includes GFP channel for transduced cells. Scale bar, 10µm.",
    "ncbi_link": "GFP: 
Smarca5: 93762"
  },
  {
    "caption": "A, Immunofluorescence staining of H3K79me3 (green) and H3S10P (red) in a single nucleus of control and Dot1l KO mESCs. DNA is stained with DAPI (blue). Scale bar, 5 µm.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "B, Example metaphase spreads in wild type and Dot1l KO mESCs showing examples of a chromosome break, premature centromere separation, and chromosome fusion (yellow boxes). Scale bar, 5 µm.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "F, Western blot for the DNA damage marker γH2A.X in control and Dot1l KO mESCs. Quantitation of signal on the blot for n=2 biological replicates is shown.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "(d) A COS-7 cell expressing EBFP2-parkin (cyan), AcGFP-sec61β (green) and TagRFP-DFCP1 (red) were treated with 10 μM CCCP for 4 h and imaged. Omegasomes (DFCP1) appeared where ER (sec61β) and impaired mitochondria (parkin) overlap. Scale bar, 10 μm.",
    "ncbi_link": "parkin: 5071
sec61β: 10952
DFCP1: 53349"
  },
  {
    "caption": "(a) A COS-7 cell expressing EBFP2-Ub (red), AcGFP-sec61β (green) and mcherry-parkin (cyan) was treated with 10 μM CCCP for 1 h and imaged. Impaired mitochondria (parkin) displayed preferentially ubiquitinated foci (white arrows) at selected regions that overlap with the ER (sec61β).",
    "ncbi_link": "parkin: 5071
sec61β: 10952"
  },
  {
    "caption": "(B) Immunoblot analysis of membrane fractions of HEK293 Flp-In cells stably overexpressing both mouse TREM2 and mouse DAP12 upon treatment with 4D9 antibody reveals increased levels of membrane-bound TREM2 similar to what can be achieved by ADAM protease inhibition using the GM6001 inhibitor. An isotype antibody was used as a negative control. Calnexin served as a loading control. Levels of membrane-bound TREM2 were quantified by MSD ELISA. Data represent the mean ± SEM (n=3). One-way ANOVA, Tukey's post hoc test; p (DMSO vs GM) = 0.0011; p (DMSO vs isotype) = 0.992; p (isotype vs 4D9) = 0.0005; n.s., not significant.",
    "ncbi_link": "TREM2: 83433
DAP12: 22177"
  },
  {
    "caption": "(C) Immunoblot analysis of conditioned media from HEK293 Flp-In cells stably overexpressing both mouse TREM2 and mouse DAP12 upon treatment with 4D9 antibody reveals decreased levels of sTREM2 similar to what can be achieved by ADAM protease inhibition using the GM6001 inhibitor. An isotype antibody was used as a negative control. sAPPα served as a loading control. Note that heavy and light chains of the antibodies used for treatment are also detected and annotated. Levels of sTREM2 were quantified by MSD ELISA. Data represent the mean ± SEM (n=3). One-way ANOVA, Tukey's post hoc test; p (DMSO vs GM) < 0.0001; p (DMSO vs isotype) = 0.6372; p (isotype vs 4D9) < 0.0001; n.s., not significant.",
    "ncbi_link": "TREM2: 83433
DAP12: 22177"
  },
  {
    "caption": "(D) 4D9 antibody selectively detects TREM2 on the cell surface of HEK293 Flp-In cells stably overexpressing mouse TREM2 and mouse DAP12. An anti-HA antibody was used as a positive control while empty vector transfected HEK293 Flp-In cells were used as a negative control. Scale bar= 10µm.",
    "ncbi_link": "TREM2: 83433
DAP12: 22177"
  },
  {
    "caption": "(A) Flow cytometry dose response curve for cell binding of 4D9 mAb (EC50= 0.29nM), 4D9 Fab (EC50=0.17nM), and isotype to HEK cells stably overexpressing mouse TREM2. Data represent the mean ± SEM (n=2).",
    "ncbi_link": "TREM2: 83433"
  },
  {
    "caption": "(C) ELISA-mediated quantification of sTREM2 in conditioned media from HEK293 cells stably overexpressing mouse TREM2 treated with a dose titration of 4D9 mAb (EC50=2.3nM), 4D9 Fab, or isotype for 18 hours. Data represent the mean ± SEM (n=3).",
    "ncbi_link": "TREM2: 83433"
  },
  {
    "caption": "(D) AlphaLISA-mediated quantification of pSYK levels in HEK293 Flp-In cells stably overexpressing mouse TREM2 and mouse DAP12 treated with a dose titration of 4D9 mAb, 4D9 Fab or isotype for 5 minutes. Data represent the mean ± SEM (n=3).",
    "ncbi_link": "TREM2: 83433
DAP12: 22177"
  },
  {
    "caption": "(E) AlphaLISA-mediated quantification of pSYK levels in HEK293 Flp-In cells stably overexpressing mouse TREM2 and mouse DAP12 or empty vector treated with 1mg/ml POPC/POPS liposomes and 20µg/ml 4D9 mAb, 4D9 Fab or isotype for 5 minutes. pSYK levels were also determined for cells treated with liposomes only. Data represent the mean ± SEM (n=3). Two-way ANOVA, Tukey's post hoc test (cell line effect: F1,16=365.7, p=<0.0001; treatment effect: F3,16=39.35, p<0.0001; cell line x treatment effect: F3,16=38.75, p<0.0001); p (no Ab vs isotype) = 0.6218; p (no Ab vs 4D9 mAb) < 0.0001; p (no Ab vs 4D9 Fab) = 0.7301; p (isotype vs 4D9 mAb) < 0.0001; p (isotype vs 4D9 Fab) > 0.9999; p (4D9 mAb vs 4D9 Fab) < 0.0001; n.s., not significant.",
    "ncbi_link": "TREM2: 83433
DAP12: 22177"
  },
  {
    "caption": "(A) Flow cytometry detection of cell surface binding of 4D9 (blue) and isotype (green) to wild type and Trem2-/- mouse bone marrow derived macrophages. Representative histograms are shown as MFI (mean fluorescent intensity). Graphs represent the median signal intensity ± SEM (n=3). Student's t-test (two-tailed); Trem2+/+: p = 0.0005; Trem2-/-: p = 0.4435; n.s., not significant.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(B) Immunoblot analysis of membrane fractions of bone marrow derived macrophages (BMDM) upon treatment with 4D9 antibody reveals increased levels of membrane-bound TREM2 relative to an isotype antibody. BMDM from TREM2 knockout mice were included to show the specificity of the anti-TREM2 antibody. Calnexin served as a loading control. Levels of membrane-bound TREM2 were quantified by MSD ELISA. TREM2 antibody clone 5F4 was used for detection. Data represent the mean ± SEM (n=5-6). Unpaired t-test (two-tailed) with Welch's correction; p<0.0001. No gender-specific differences could be observed.",
    "ncbi_link": "TREM2: 83433"
  },
  {
    "caption": "(C) Immunoblot analysis of sTREM2 in conditioned media from BMDM upon treatment with 4D9 and isotype antibodies. BMDM from TREM2 knockout mice were included to show the specificity of the anti-TREM2 antibody. Soluble APP served as a loading control. Note that heavy and light chains of the antibodies used for treatment are also detected and annotated as follows: Ab hc= antibody heavy chain; Ab lc= antibody light chain. Levels of sTREM2 were quantified by MSD ELISA. TREM2 antibody clone 5F4 was used for detection. Data represent the mean ± SEM (n=6). Unpaired t-test (two-tailed) with Welch's correction; p<0.0001. No gender-specific differences could be observed.",
    "ncbi_link": "TREM2: 83433"
  },
  {
    "caption": "(D) Wildtype, Trem2+/-, and Trem2-/- BMDMs were plated in low concentration of M-CSF on 4D9 or isotype coated wells for 5 days and cellular ATP levels were measured by luminescence detection to indicate cell viability. 4D9 and isotype data for each genotype represent the mean ± SEM (n=2 and n=1, respectively).",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(A) Flow cytometry detection of cell surface 4D9 (red) binding and isotype control (blue) on primary wild type and Trem2-/- mouse microglia. Data are shown as MFI (mean fluorescent intensity).",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(B) Immunohistochemical costainings of TREM2 (magenta) and IBA1 (green) microglia in the cortex of isotype control and 4D9 injected WT and APP-NL-G-F mice. Side panel shows images from each staining at a larger magnification indicated by the dotted white boxes. Scale bar = 10µm; scale bar (inset) = 2.5µm.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(C) Quantification of cortical TREM2 stainings shown in B. Two-way ANOVA, Tukey's multiple comparison test (Genotype effect: F1,23=70.63, p=<0.0001; Treatment effect: F1,23=14.33, p=0.0010; Genotype x Treatment effect: F1,23=14.51, p=0.0009); p (WT isotype vs WT 4D9) > 0.9999; p (WT isotype vs APP isotype) = 0.02; p (WT 4D9 vs APP 4D9) < 0.0001; p (APP isotype vs APP 4D9) = 0.0001; n.s., not significant.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(D) Quantification of cortical IBA1 staining shown in B. Two-way ANOVA, Tukey's multiple comparison test (Genotype effect: F1,21=215.4, p=<0.0001; Treatment effect: F1,21=0.5994, p=0.4475; Genotype x Treatment effect: F1,21=0.2992, p=0.5902); p (WT isotype vs APP isotype) < 0.0001; p (WT 4D9 vs APP 4D9) < 0.0001; p (APP isotype vs APP 4D9) = 0.9986; n.s., not significant.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(F) Quantification of P2RY12 stained cells in the cortex shown in E. Two-way ANOVA, Tukey's multiple comparison test (Genotype effect: F1,23=71.99, p=<0.0001; Treatment effect: F1,23=9.029, p=0.0063; Genotype x Treatment effect: F1,23=5.93, p=0.0231); p (WT isotype vs APP isotype) = 0.0018; p (WT null vs APP 4D9) < 0.0001; p (APP isotype vs APP 4D9) = 0.0051.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A, B) Overview of the cortex immunohistochemically stained for Aβ plaques in 6 months old APP-NL-G-F mice treated with isotype control (A) and 4D9 antibody (B). Scale bar= 100µm.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(C) Higher magnification images of cortical Aβ plaques in APP isotype and 4D9 injected mice. Scale bar= 10µm. (D) Quantification of cortical plaque area from stainings shown in C. Mann-Whitney U test, p=0.0082. (E) Quantification of total plaque coverage of Aβ stainings in the cortex shown in C. Mann-Whitney U test, p=0.014.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(F) Immunoblot analysis of soluble (DEA fraction, top) and insoluble Aβ levels (FA fraction, bottom) in brains of APP-NL-G-F mice treated with either isotype control or 4D9 antibody. While a reduction in levels of soluble Aβ is evident from the DEA fractions no change in levels of insoluble Aβ could be detected in the FA fractions. Note that the higher background in the DEA immunoblot is due to a much longer exposure time, which was needed to visualize soluble Aβ.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "Defects in midbrain-type dopamine (mDA) neuron-specific developmental factor expressions in the ventral midbrain (VM) of Lin28a/b cKO embryos. Embryonic VM sections from 3 WT and cKO animals each were immunoflorescent stained for the midbrain-specific markers in parallel and mean fluoresecent intensities (MFI) were measured. n = 20 cells for each group. *** p<0.0001, t-test. Reduced mDA neurons in the embryonic VM (E12.5) and adult SN at 2-7 months (young age) and at 14-18 months (old age) of the Lin28a/b cKO mice. *p<0.05, **p<0.005, n=4 each wild-type (WT) and cKO embryos, and 9 (WT), 8 (cKO) in adult mice. Enhanced DA transporter (DAT)+ and TH+ fiber intensities of Lin28a/b cKO adult mice (age: 4-7 months). Striatal sections of WT and cKO mice (3 animals for each group) were subjected to immunofluorescent staining against DAT and TH in parallel, and MFI was measured from 101 microscopic fields of dorsolateral striatum.",
    "ncbi_link": "Lin28a: 83557"
  },
  {
    "caption": "Enhanced susceptibility of Lin28a/b cKO mice to the Parkinsonian toxin MPTP. WT and cKO mice were injected with MPTP (20mg/kg, i.p) for 5 days and behaviors of the animals were assessed for 1 month after the MPTP injection",
    "ncbi_link": "Lin28a: 83557"
  },
  {
    "caption": "Enhanced susceptibility of Lin28a/b cKO mice to the Parkinsonian toxin MPTP. The mouse brains at 1 month after initial MPTP exposure were subjected to immunohistochemical analyses for TH+ mDA neuron counts at SN (L) and DAT MFI at striatum (M).",
    "ncbi_link": "Lin28a: 83557"
  },
  {
    "caption": "Accumulation of α-synuclein oligomers analyzed by western blotting. The mutant (c13) and corrected (c22) neural stem cells (NSCs) were transduced with α-synuclein-expressing lentiviruses. At 6 days after differentiation, cells were extracted and fractionated to Triton X-100 (1%)-soluble and insoluble fractions. Shown is the representative WB image of three independent experiments. α-Synuclein oligomers are indicated with a bracket, while monomer bands are marked with an arrowhead.",
    "ncbi_link": "α-synuclein: "
  },
  {
    "caption": "LIN28A protein stability assays. HEK293 cells were transfected with pFLAG-WT-LIN28A and pFLAG-LIN28A R192G. Protein samples were prepared during 24 h of cycloheximide (50 μg/ml) treatment. Representative western blot data for LIN28A protein level changes normalized to β-actin protein levels (upper) or with normalization based on initial (0 h) LIN28A protein levels (lower). Band intensities were quantified using ImageJ, and normalized values are depicted (lower graph) (n=5).",
    "ncbi_link": "FLAG: 
LIN28A: 79727"
  },
  {
    "caption": "The proteasome inhibitor MG132 treatment increases LIN28A(R192G) protein level. After serum starvation for 3 hours, HEK293T cells expressing LIN28A(R912G) were treated with or without MG132 (0.1-10 uM) for 30 minutes, and then followed by WB analyses.",
    "ncbi_link": "LIN28A: 83557"
  },
  {
    "caption": "Cytoplasmic localization of WT LIN28A and LIN28A(R192G) proteins. HeLa cells transfected with pFLAG-WT-LIN28 and pFLAG-LIN28A(R192G) were stained with FLAG antibody and counterstained with DAPI.",
    "ncbi_link": "FLAG: 
LIN28: 79727
LIN28A: 83557"
  },
  {
    "caption": "LET-7 microRNA regulatory activity of LIN28A. HeLa cells were transfected with plasmids expressing FLAG-tagged WT- LIN28A, LIN28AR192G, or mock pFLAG vector (control), and Let-7a, b, and c levels were quantified by RT-qPCR. The level of RNA was normalized to that of U6 snRNA. p<0.05, n=26 from 6 independent experiments, ns = not significant, ANOVA.",
    "ncbi_link": "FLAG: 
U6: 
LIN28A: 79727
Let-7a: 406881
LET-7: 406885///406884///406881"
  },
  {
    "caption": "Affinity of LIN28A protein binding to its cognate mRNA 3′UTR region. Upper: schematic for pmirGLO-LIN28A used in this assay, a bicistronic Firefly/Renilla luciferase (FLuc/RLuc) plasmid containing the part of the LIN28A 3′UTR containing the putative LIN28A protein binding sites (black dots)Wilbert et al., 2012(). Lower: HeLa cells were transiently co-transfected with pmirGLO-LIN28A 3′UTR along with pFLAG-WT-LIN28A, pFLAG-LIN28A R192G, or mock pFLAG control. LIN28A protein-mRNA binding activities were determined by relative luciferase activity levels of FLuc normalized to those of RLuc. *p<0.05, n=18 from 6 independent experiments.",
    "ncbi_link": "FLAG: 
FLuc: 
Renilla luciferase: 
RLuc: 
LIN28A: 79727"
  },
  {
    "caption": "LIN28A-RHA co-IP assays in HEK293 cells transfected with pFLAG-WT-LIN28A and pFLAG-LIN28A R192G.",
    "ncbi_link": "FLAG: 
LIN28A: 79727"
  },
  {
    "caption": "Macrophages transduced with non-specific scrambled shRNA (shNS) or TLR8 shRNA (shTLR8) were treated for 24 h with CL097, ssRNA40, ssRNA41 or rapamycin (Rapa). (A) Cells were lysed and immunoblot performed with antibodies to TLR8 and β-actin.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "A-B) Macrophages were treated for 24 h with CL097, ssRNA40 or ssRNA41. (A) Top, qRT-PCR for CYP27B1 after 6 h. Bottom, immunoblots of CYP27B1 using antibody to CYP27B1 or β-actin.",
    "ncbi_link": "CYP27B1: 1594"
  },
  {
    "caption": "(B) Top, qRT-PCR for VDR after 6 h. Bottom, immunoblots of VDR using antibody to VDR or β-actin.",
    "ncbi_link": "VDR: 7421"
  },
  {
    "caption": "(C-D) Macrophages transduced with non-specific scrambled shRNA (shNS), CYP27B1 shRNA (shCYP27B1) or VDR shRNA (shVDR) were treated for 24 h with CL097, ssRNA40, ssRNA41 or rapamycin (Rapa). (C) Left, immunoblots performed with antibodies to CYP27B1, VDR and β-actin. Right, immunoblots of LC3B isoforms using antibody to LC3B or β-actin.",
    "ncbi_link": "CYP27B1: 1594
VDR: 7421"
  },
  {
    "caption": "Macrophages transduced with non-specific scrambled shRNA (shNS) or CEBPB shRNA (shCEBPB) were treated for 24 h with CL097, ssRNA40, or ssRNA41. (A) Cells were lysed and immunoblot performed with antibodies to CEBPB and β-actin.",
    "ncbi_link": "CEBPB: 1051"
  },
  {
    "caption": "(A) Macrophages transduced with non-specific scrambled shRNA (shNS), TLR8 shRNA (shTLR8), CYP27B1 shRNA (shCYP27B1), or VDR shRNA (shVDR) were treated with CL097 for 24 h before infection with HIV with continuous CL097 treatment. Top, immunoblot analysis performed using antibodies raised to TLR8, CYP27B1, VDR and β-actin. Bottom, ELISA performed for extracellular release of HIV p24 antigen over 10 d. Results are reported as mean ± s.e.m., n = 4.",
    "ncbi_link": "CYP27B1: 1594
TLR8: 51311
VDR: 7421"
  },
  {
    "caption": "TLR8-mediated inhibition of HIV is autophagy dependent.(A-B) Macrophages transduced with BECN1 shRNA (shBECN1) (A) or ATG5 shRNA (shATG5)",
    "ncbi_link": "ATG5: 9474
BECN1: 8678
TLR8: 51311"
  },
  {
    "caption": "(B) were incubated with CL097 for 24 h before infection with HIV with continuous CL097 treatment for 10 d. Right, immunoblot analysis performed using antibodies raised to BECN1, ATG5 and β-actin. Left, ELISA performed for extracellular release of HIV p24 antigen over 10 d. Results are reported as mean ± s.e.m., n = 4.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(A) Macrophages were treated with CL097, ssRNA40, ssRNA41 for 6 h after which qRT-PCR for CAMP was performed. Results are reported as mean ± s.e.m., n = 4.",
    "ncbi_link": "CAMP: 820"
  },
  {
    "caption": "(B) Macrophages were treated for 24 h with CL097 or ssRNA40 in the presence of 45 nmol/L or 100 nmol/L 25D3. Left, qRT-PCR for CAMP performed after 6 h. Results are reported as mean ± s.e.m., n = 4. Right, after 24 h cells were stained with anti-CAMP antibodies and analyzed by flow cytometry. Representative histograms from three donors are shown.",
    "ncbi_link": "CAMP: 820"
  },
  {
    "caption": "(C) Macrophages transduced with non-specific scrambled shRNA (shNS) or CAMP shRNA (shCAMP) were incubated with CL097, rapamycin (Rapa) or vehicle control for 24 h. Top, immunoblot analysis performed using antibodies raised to CAMP and β-actin. Bottom, immunoblots of LC3B isoforms using antibody to LC3B or β-actin.",
    "ncbi_link": "CAMP: 820"
  },
  {
    "caption": "U2OS cells transfected with siCTL, or siDDX5 were subjected to DRIP-qPCR analysis with anti-IgG, and anti-S9.6 antibodies with or without RNaseH treatment. The gene location and genomic qPCR amplification region are shown at the top of each panel. B, E, H, S and X denote the location of the BsrGI, EcoRI, HindIII, SspI, and XbaI. The identified R-loop peaks were extracted from the R-loop database (R-loop DB) for each region. The bar graphs are the average and S.E.M. from 3 independent experiments. Statistical significance was assessed using t-test. *: p < 0.05.",
    "ncbi_link": "DDX5: 1655"
  },
  {
    "caption": "HEK293 cells transfected with Flag-DDX5 were lysed and immunoprecipitated with anti-Flag antibodies. The bound proteins were along with WCE from untransfected (-) and Flag-DDX5 (+) transfected cells were Western blotted with anti-FLAG, anti-methylarginine antibodies (MeR).",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "Representative images of S9.6 staining in siCTL, siDDX5, or siPRMT5 knockdown at transcription on (TA-KR) or off (TetR-KR) genomic loci in U2OS TRE cells. The nuclei are visualized by DAPI.",
    "ncbi_link": "KR: 
DDX5: 1655
PRMT5: 10419"
  },
  {
    "caption": "U2OS cells transfected with siCTL or siPRMT5 were subjected to DRIP-qPCR analysis. The average and S.E.M. from 3 independent experiments is shown. Statistical significance was assessed using Student's t-test. *: p < 0.05; and **: p < 0.01.",
    "ncbi_link": "PRMT5: 10419"
  },
  {
    "caption": "Western blotting of whole cell extracts from siCTL, siPRMT5, siDDX5 or siDDX5/ siPRMT5 transfected cells.",
    "ncbi_link": "DDX5: 1655
PRMT5: 10419"
  },
  {
    "caption": "U2OS cells transfected with siCTL, siPRMT5, siDDX5 or siDDX5/ siPRMT5 were subjected to DRIP-qPCR analysis. The average and S.E.M. from 3 independent experiments is shown. Statistical significance was assessed using Student's t-test. *: p < 0.05; and **: p < 0.01.",
    "ncbi_link": "DDX5: 1655
PRMT5: 10419"
  },
  {
    "caption": "U2OS cells were transfected with a Flag-DDX5 expression vector in the presence of siCTL or siPRMT5. Lysates were immunoprecipitated with IgG or anti-Flag antibodies as indicated. The WCE and the bound proteins were Western blotted with anti-symmetrical dimethylarginine antibody or anti-Flag antibodies.",
    "ncbi_link": "Flag: 
DDX5: 1655
PRMT5: 10419"
  },
  {
    "caption": "Immunofluorescence analysis with S9.6 and anti-Flag antibodies of U2OS cells transfected with Flag-tagged DDX5, DDX5-RK or DDX5-XD (helicase dead). Nuclear S9.6 signal was counted in both Flag-negative and Flag-positive cells. The Flag-negative cells were considered as untransfected cells. The graphs shown represent the quantification with the S.E.M from 3 independent experiments. Statistical significance was assessed using one-way ANOVA t-test. ****, p < 0.0001.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "Immunofluorescence analysis with S9.6 and anti-Flag antibodies of U2OS cells transfected with siCTL or siDDX5-1 and Flag-tagged DDX5 (+WT) or DDX5-RK (+RK) as indicated. The graphs show the average and S.E.M. from three independent experiments. Statistical significance was assessed using one-way ANOVA t-test. ****, p < 0.0001.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL, or siDDX5. The next day, the cells that received siDDX5 were subsequently transfected with empty pcDNA3 vector (-), expression vectors encoding Flag-DDX5 (WT), or Flag-DDX5-RK (RK). Forty eight hours later, all the cells were subjected to DRIP-qPCR analysis. The average with the S.E.M. from 3 independent experiments is shown. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and n.s.: not significant.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "HEK293 cells were transfected with empty pcDNA3 vector (-) or Flag-DDX5 (+). Whole cell lysates (WCE) and anti-Flag immunoprecipitations (IP) were immunoblotted with anti-Flag and anti-XRN2 antibodies.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "U2OS cells were transfected with empty pcDNA3 vector (pcDNA3) or expression vectors encoding Flag-DDX5 WT (1-614) or truncated Flag-DDX5 proteins (60-614; 1-554; 1-435). WCE of the transfected cells (left panel) were Western blotted with anti-Flag and anti-XRN2 antibodies to confirm equivalent expression. The transfected cells were lysed and anti-Flag immunoprecipitations (right panel) performed for the presence of co-immunoprecipitating endogenous XRN2 by Western blotting with anti-XRN2 antibodies. M denotes molecular mass markers in kDa.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "Untransfected and U2OS stably expressing Flag-DDX5 WT or Flag-DDX5-RK were subjected to immunoprecipitation with anti-Flag antibody. The WCE and the anti-Flag immunoprecipitated proteins were Western blotted with anti-monomethylarginine (MeR), anti-Flag and anti-XRN2 antibodies, respectively. M denotes molecular mass markers in kDa.",
    "ncbi_link": "Flag: 
DDX5: 1655"
  },
  {
    "caption": "U2OS cells transfected with siCTL, siDDX5, or siXRN2 were subjected to DRIP-qPCR analysis with anti-IgG, and anti-S9.6 antibodies with or without RNaseH treatment. The average and S.E.M. from 3 independent experiments is shown. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01.",
    "ncbi_link": "DDX5: 1655
XRN2: 22803"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL, siDDX5, or siXRN2. The gene location and qPCR amplification region are shown at the top of each panel. The identified R-loop peaks were extracted from R-loop database (R-loop DB) for each gene region. R-loop: DRIP denotes anti-S9.6 DRIP-qPCR and Pol II ChIP denotes RNA pol II ChIP. The bar graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and ****: p < 0.0001. B, E, H, S and X denote the location of the BsrGI, EcoRI, HindIII, SspI, and XbaI.",
    "ncbi_link": "DDX5: 1655
XRN2: 22803"
  },
  {
    "caption": "Schematic representation of the β-actin locus and the location of the genomic PCR primers used for ChIP-qPCR and DRIP-qPCR. Prom (promoter), RB (region B), poly(A) and RD (region D) indicate the regions analyzed by qPCR.",
    "ncbi_link": "β-actin: 60"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL or siDDX5 and XRN2 ChIP assays were performed. The XRN2 ChIP signal was normalized to the Pol II ChIP signal. WCE were immunoblotted with anti-DDX5 and α-tubulin antibodies, the latter was used as a loading control. The graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01.",
    "ncbi_link": "DDX5: 1655
XRN2: 22803"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL, siDDX5 or siXRN2. The cells were subjected to Western blotting, RNA Pol II ChIP and DRIP analysis of β-actin gene. The graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and ****: p < 0.0001.",
    "ncbi_link": "β-actin: 60
DDX5: 1655
XRN2: 22803"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL or siDDX5. The next day, the cells that received siDDX5 were subsequently transfected with empty pcDNA3 vector (-), expression vectors encoding Flag-DDX5 (WT), or Flag-DDX5-RK (RK). The cells were subjected to Western blotting to visualize Flag-DDX WT and RK expression. Pol II ChIP and DRIP analysis of β-actin gene were performed. For the ChIP analysis, the Y-axis shows the signal-to-noise ratio of RNA Pol II IP relative to control IgG IP. The graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and ****: p < 0.0001.",
    "ncbi_link": "Flag: 
β-actin: 60
DDX5: 1655"
  },
  {
    "caption": "HEK293 cells were transfected with siCTL or siPRMT5. The cells were subjected to Western blotting, RNA Pol II ChIP and DRIP analysis of β-actin gene. The graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01.",
    "ncbi_link": "β-actin: 60
PRMT5: 10419"
  },
  {
    "caption": "HEK293 cells were transfected with empty plasmid (-), wild type Flag-DDX5 (WT) or its RK mutant (RK) and subjected to western blot and Flag-DDX5 ChIP-qPCR analysis of β-actin gene. The graphs show the average and S.E.M. from at least three independent experiments. Statistical significance was assessed using Student's t-test. *: p < 0.05; **: p < 0.01 and ****: p < 0.0001; n.s. not significant.",
    "ncbi_link": "Flag: 
β-actin: 60
DDX5: 1655"
  },
  {
    "caption": "B Immunoblot  showing CDK5RAP2  levels in Cdk5rap2  wild-type (WT), heterozygous (HET) and null erythroid progenitors (EPs) isolated from fetal livers. Actin  was used as loading control. ** indicates nonspecific band. C Quantification of mean protein levels from (B). Numbers in brackets correspond to number of embryos  analyzed. Data information: Bar graphs display mean ± s.d. Statistical analysis was based on the number of embryos  (C, Statistical significances were determined by One-way ANOVA test with Tukey's (C, test *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001.",
    "ncbi_link": "Cdk5rap2: 214444"
  },
  {
    "caption": "D Immunofluorescence  images of Cdk5rap2  WT, HET and null erythroid progenitors  isolated from fetal livers. Progenitors  were stained  for CDK5RAP2 (grey), γ-tubulin (magenta) and DNA   (Hoechst, blue). Images are maximum intensity projections of deconvolved z-stacks. Scale bar, 3 μm. Insets show higher magnification of centrosomes. Scale bar, 1 μm. E Quantification of mean centrosomal  signal intensities of CDK5RAP2  and γ-tubulin from (D). Numbers in brackets correspond to number of embryos  analyzed with a total number of 470 (WT), 406 (HET) and 379 (null) progenitors. Data information: Bar graphs display mean ± s.d. Statistical analysis was based on the number of embryos  E, Statistical significances were determined by One-way ANOVA test with Tukey's E, test *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001.",
    "ncbi_link": "Cdk5rap2: 214444"
  },
  {
    "caption": "C Immunofluorescence  images of  Cdk5rap2HET and Cdk5rap2null cells at 36 hours (T36) of ex vivo culture. Representative examples for different mitotic spindle morphologies are shown. Cells were stained  for α-tubulin (magenta),  γ-tubulin (grey), pHH3 (green) and DNA  (Hoechst, blue). Images are maximum intensity projections of deconvolved z-stacks. Scale bar, 2 μm. D Quantification of  mitotic spindle morphology at T24 or T36 of ex vivo culture. Graph depicts percentage of spindle  phenotypes. At T24, 3  Cdk5rap2WT (323 cells), 3 Cdk5rap2HET (296 cells) and 2  Cdk5rap2null (197 cells) embryos  were analyzed. At T36, 5 Cdk5rap2WT (387 cells), 6 Cdk5rap2HET (384 cells) and 3 Cdk5rap2null (202 cells) embryos were analyzed. Data information: Bar graphs display mean ± s.d. Statistical analysis was based on the number of embryos  (D, Statistical significance was determined by One-way ANOVA with Tukey's multiple comparisons test D, *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001.",
    "ncbi_link": "Cdk5rap2: 214444"
  },
  {
    "caption": "A Immunoblot  analysis of TP53, P27  and P21  levels in ex vivo cultured Cdk5rap2 wild-type (WT), heterozygous (HET) and null EBs  after 24 (T24) and 48 (T48) hours. GAPDH  was used as loading control. ** indicates unspecific band. B Quantification of mean protein levels from (A). Numbers in brackets represent number of embryos  analyzed. Data information: Box plots show 5th,95th (whiskers) and 25th, 50th and 75th percentile (boxes). All statistical analysis were based on number of embryos. All statistical significances were determined by One-way ANOVA with Tukey's multiple comparisons test.*P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001.",
    "ncbi_link": "Cdk5rap2: 214444"
  },
  {
    "caption": "B-E (B, D) Representative microscopy images of the mitochondrial network morphology in neurons of the amygdala (B) and the CA1 region of the hippocampus (D) in mitoCFP+/P301L- mice and mitoCFP+/P301L+ mice. MitoCFP signal is displayed in gray on the images. Gray scale bars: 5 µm. (C, E) Mitochondrial length in neurons of the amygdala (C) and in Ca1 (E) of mitoCFP+/P301L- and mitoCFP+/P301L+ mice. Data information: Values represent the mean ±SEM of n=11 MitoCFP+/P301L- mice and n= 13 MitoCFP+/P301L+ mice. Each gray open circle represents the mean of 6 technical replicates (data from 6 images) per animal. * P<0.05, ** P<0.01, Student unpaired t-test.",
    "ncbi_link": "CFP: "
  },
  {
    "caption": "F-I (F, H) Representative microscopy images of the endoplasmic reticulum stained with calnexin (in red) and mitochondria (mitoCFP) in neurons of the amygdala (F) and Ca1 (H) in mitoCFP+/P301L- and mitoCFP+/P301L+ mice. (G, I) Colocalization analysis between calnexin and mitoCFP in neurons of the amygdala (G) and Ca1 (I) of mitoCFP+/P301L- and mitoCFP+/P301L+ mice. The Manders' overlap coefficients M2 is represented on the graphs, as it indicates the proportion of overlaps between the mitoCFP signal (channel 2) and calnexin signal (channel 1) relative to the total pixel intensity of channel 2 (i.e. only in neurons, as mitoCFP is expressed only in these cells). Data information: Values represent the mean ±SEM of n=11 MitoCFP+/P301L- mice and n= 13 MitoCFP+/P301L+ mice. Each gray open circle represents the mean of 6 technical replicates (data from 6 images) per animal. * P<0.05, ** P<0.01, Student unpaired t-test.",
    "ncbi_link": "CFP: "
  },
  {
    "caption": "A Representative microscopy images (z-projections) of the mitochondrial network stained with TOMM20 in SH-SY5Y cells stably expressing a green fluorescent protein (GFP)-tagged wild-type form of tau protein (wtTau-GFP), a GFP-tagged P301L mutant form of tau protein (P301L-GFP) or cell expression the GFP only (control cells = WT-GFP). GFP signal is displayed in gray on the images, TOMM20 signal is in red, and the nuclei are delimited by white dotted lines. B-C Mitochondrial length (B) and percentage of mitochondria in the perinuclear area (C) in WT-GFP, wtTau-GFP and P301L-GFP expressing cells. On average 1,000-2,500 mitochondrial organelles were analyzed per group (n = 20-25 images per group, 3 independent experiments). Data information: Data are presented as mean ±SEM. White scale bars: 20 µm B-C * P<0.05, ** P<0.01, ***P<0.001; One-way ANOVA + Tukey's post hoc test. TOMM20: translocase of the outer mitochondrial membrane complex subunit 20",
    "ncbi_link": "GFP: 
green fluorescent protein: 
Tau: 4137
tau: 4137"
  },
  {
    "caption": "Visualization of the IP3R-VDAC (D), IP3R-GRP75 (E) interactions by in situ proximity ligation assay (PLA) WT-GFP, wtTau-GFP and P301L-GFP expressing cells. Interactions between the two targeted proteins are depicted in red (63X magnification) and cell surfaces are delimited by a white line. Data information: Data are presented as mean ±SEM. White scale bars: 20 µm GRP75: glucose-regulated protein 75 IP3R: inositol trisphosphate receptor VDAC: voltage-dependent anion channel.",
    "ncbi_link": "GFP: 
Tau: 4137"
  },
  {
    "caption": "G-I Quantitative analysis of the PLA signal represented as number of contact points between IP3R­VDAC (G), IP3R-GRP75 (H) and VAPB-PTPIP51 (I) per cell in percentage of the WT-GFP cells. In total, 60-75 cells were analyzed per group (5 independent experiments). Data information: Data are presented as mean ±SEM. White scale bars: 20 µm G-I * P<0.05, ** P<0.01, ***P<0.001; One-way ANOVA + Tukey's post hoc test. GRP75: glucose-regulated protein 75 PTPIP51: protein tyrosine phosphatase-interacting protein 51 VDAC: voltage-dependent anion channel.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "K-L Mitochondrial length (K) and percentage of mitochondria in the perinuclear area (L) in WT cells and Tau KO cells. On average 1,000-2,500 mitochondrial organelles were analyzed per group (n = 20-25 images per group, 3 independent experiments). Data information: Data are presented as mean ±SEM. White scale bars: 20 µm * P<0.05, ***P<0.001; Student unpaired t-test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "P-R Visualization of the IP3R-VDAC (P), IP3R-GRP75 (Q) and VAPB-PTPIP51 (R) interactions by in situ PLA in WT and Tau KO cells. Interactions between the two targeted proteins are depicted in red (63X magnification) and cell surfaces are delimited by a white line. Data information: Data are presented as mean ±SEM. White scale bars: 20 µm * P<0.05, ***P<0.001; Student unpaired t-test. GRP75: glucose-regulated protein 75; IP3R: inositol trisphosphate receptor; PTPIP51: protein tyrosine phosphatase-interacting protein 51 VAPB: vesicle-associated membrane protein-associated protein B VDAC: voltage-dependent anion channel.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "G Quantification of total cholesterol levels in cell lysates from WT, P301L and Tau KO cells. Data information: (G Data are presented as mean ±SEM of n = 12-18 replicates per group (4 independent experiments) in percentage of the WT cells. * P<0.05, ***P<0.001; One-way ANOVA + Tukey's post hoc test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "K-N Mitochondrial cholesterol levels (K, L) and pregnenolone levels (M, N) in WT, P301L and Tau KO cells (K, M) and in brain preparations from WT and pR5 mice (L, N). Data information: K, M) Data are presented as mean ±SEM of n = 12-18 replicates per group (4 independent experiments) in percentage of the WT cells. * P<0.05, ***P<0.001; One-way ANOVA + Tukey's post hoc test. L, N) Data are presented as mean ±SEM of n = 6 WT and n = 5 pR5 mice with 2 technical replicates per animal. * P<0.05, ** P<0.01, Student unpaired t-test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "O-Q Quantification of total cholesterol levels (O), mitochondrial cholesterol levels (P) and pregnenolone levels (Q) in patient-derived induced pluripotent stem cells (iPSC) bearing a P301L tau mutation (iPSC-P301L) and the corresponding isogenic wild-type cells (iPSC-WT). (O-Q) Data are presented as mean ±SEM of n = 27 replicates/group (O), n = 9 replicates/group (P) and n = 18 replicates/group (Q). * P<0.05, *** P<0.001, Student unpaired t-test.",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "A Visualization of the VAPB-PTPIP51 interactions by in situ proximity ligation assays (PLAs) in wild-type (WT) cells and P301L cells transfected with the control (Ctrl) siRNA, as well as in MFN2 siRNA transfected cells. Interactions between the two targeted proteins are depicted in red (63X magnification) and cell surfaces are delimited by a white line. White scale bars: 20 µm B Quantitative analysis of the PLA signal represented as number of contact points between VAPB-PTPIP51 per cell in percentage of the WT cells. In total, 60 cells were analyzed per group (4 independent experiments). Data information: Data are presented as mean ± SEM. * P<0.05, ** P<0.01, ***P<0.001; One-way ANOVA + Tukey's post hoc test. PTPIP51: protein tyrosine phosphatase-interacting protein 51 VAPB: vesicle-associated membrane protein-associated protein B.",
    "ncbi_link": "MFN2: 9927"
  },
  {
    "caption": "A-D (A, C) Representative microscopy images (z-projections) of tau phosphorylation using (A) AT8 and (C) AT180 antibodies (in red) in GFP-tagged P301L cells (GFP signal in gray) treated for 24 h with CHIR99021 (CHIR) (right) and untreated cells (left). White scale bars: 25 µm. (B, D) Quantification of (B) AT8 and (D) AT180 staining fluorescence intensity. Data are presented as mean ±SEM of n = 50-60 cells per group (4 independent experiments). *** P<0.001; Student unpaired t-test. Data information: Data are presented as mean ±SEM of n = 50 replicates per group (5 independent experiments) in percentage of the WT cells.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "E qRT-PCR of proliferation, stem cell and differentiation markers (CCND1, PTEN, SOX2, NOTCH1, NESTIN, MYC) in BT168FO cells after 48 h Dox treatment, compared to uninduced cells (n = 3; mean ± SD). Expression levels in non-induced cells were set as 1.",
    "ncbi_link": "CCND1: 595
MYC: 4609
NESTIN: 10763
NOTCH1: 4851
PTEN: 5728
SOX2: 6657"
  },
  {
    "caption": "A-B Seqminer heatmaps of MYC and Omomyc levels around TSSs of all MYC promoter-target genes in BT168FO (A) cells, treated or not with Dox for 24 h. TSS regions are ranked by decreasing MYC occupancy in untreated cells. Each row shows the ± 5 kb region centred on TSSs. Colour scaled intensities are in units of tags per 50bp. The plots adjacent to each heatmap depict MYC and Omomyc binding patterns at genes in the two gene clusters denoted by arrows, in cells treated or not with Dox.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "A-B Seqminer heatmaps of MYC and Omomyc levels around TSSs of all MYC promoter-target genes in U87FO (B) cells, treated or not with Dox for 24 h. TSS regions are ranked by decreasing MYC occupancy in untreated cells. Each row shows the ± 5 kb region centred on TSSs. Colour scaled intensities are in units of tags per 50bp. The plots adjacent to each heatmap depict MYC and Omomyc binding patterns at genes in the two gene clusters denoted by arrows, in cells treated or not with Dox.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "A Heatmap of RNA Pol II levels around TSSs of MYC promoter-target genes in BT168FO cells, treated or not with Dox for 24 h. TSS regions are ranked by decreasing MYC occupancy in untreated cells. Each row shows the ± 5 kb region centred on TSSs. Colour scaled intensities are in tags/50bp.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "B Tracks of Pol II binding signals (ChIP-seq) at NCL, miR-17-92, OLIG2, HDAC1, and DUSP10 genes in BT168FO cells treated or not with Dox for 24 h. The y-axis shows Pol II binding signals as tags/500bp/million reads. The x-axis displays genomic positions; introns as lines, exons as boxes. Arrowheads denote direction of transcription. Blue and green bars denote the presence of MYC or Omomyc peaks. Grey boxes are TSS regions.",
    "ncbi_link": "DUSP10: 11221
HDAC1: 3065
miR-17-92: 407975
MYC: 4609
NCL: 4691
OLIG2: 10215"
  },
  {
    "caption": "A Promoter occupancy by MYC correlates with transcript levels in cells untreated with doxycycline (black line). In doxycycline treated cells promoter occupancy by MYC is lower, and no longer increases together with transcript levels. The scatter plot displays MYCChIP-seq reads at promoters (-1000, +100 regions with respect to TSS) in BT168FO cells - untreated (black) or upon 48 h Dox treatment (blue) - versus transcript levels (FPKM from RNA-seq data).",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "D Transcript level distribution of MYC promoter-targets significantly down (red dots) or up (green dots) modulated in cells treated with Dox for 24 h vs. untreated cells. Transcript levels, expressed as FPKM, represent averages of three independent experiments.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "A RNA-seq expression values of select genes in BT168FO GSCs along a 48 h time course of Omomyc induction (n = 3 independent biological replicates). The block on the left represents DUSP (dual specificity phosphatase) family genes. The middle block contains transcription factors (TFs): the upper thirteen (ASCL1-SALL1) are GSC-specific and the remaining ones are oncogenic. The right block contains genes, including well-known MYC targets, with functions in proliferation, neurodifferentiation, and gliomagenesis. The first column of each block represents the average expression (log2 FPKM) in untreated cells (0 h) in the colour scale illustrated by the lower bar: violet indicates low and blue high expression. The other columns depict relative expression versus untreated cells (average log2 FC) at different times (8-48h) of Dox treatment, according to the scale shown by the upper bar: red indicating low and green high expression. The table in the upper left summarizes the GSEA score of the set 19 GSC-specific transcription factors [40], showing a significant downregulation by Omomyc.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "B Enrichment plots obtained by GSEA (Gene Set Enrichment Analysis) of RNA-seq data from BT168FO cells. Left: genes downregulated by Omomyc in BT168FO identify the set of genes targeted by the GSC core TFs [40]. Middle: Omomyc downregulated genes identify a gene set upregulated by MYC in cancer cells [66]. Right: genes upregulated by Omomyc identify genes downregulated in small cell lung cancers carrying MYC amplification [2]. .",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "C RT-qPCR expression analysis of selected miRs in U87FO cells grown 48 h in the presence (+) or absence (-) of Dox (n = 3; mean ± SD). Expression levels were normalized using U6RNA as control. Expression levels in non-induced cells were set as 1.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "E EGFR, ZEB1, and GAPDHimmunoblots in uninduced U87FO cells (-) and in cells transfected with LNA oligos targeting miR-200a-200b-429 (LNA 200) and miR-146b (LNA 146b), or with a non-targeting LNA (C), and induced with Dox for 48 h (+Dox). Representative images are shown.",
    "ncbi_link": "miR-146b: 574447"
  },
  {
    "caption": "F MTS cell proliferation assay of uninduced or Dox induced U87FO cells, transfected with either a non-targeting LNA (LNA C), or LNA oligos targeting the miR-200a-200b-429 cluster (LNA 200), miR-146b (LNA 146b), or both (LNAmix) and analysed at 24, 48 and 72h (n = 3; mean ± SD).",
    "ncbi_link": "miR-146b: 574447"
  },
  {
    "caption": "(A). Cell growth assessment of ΔIndLon (upper plot) and ΔIndFtsH (lower plot) mutants grown under inducing (blue) or depleting conditions (red). Growth was monitored by measuring DNA and protein biomass over time. The average from two independent biological replicates is shown.",
    "ncbi_link": "FtsH: 45596573
Lon: 45596210"
  },
  {
    "caption": "(D). Role of Lon and FtsH under heat shock stress conditions. ΔIndLon and ΔIndFtsH mutants were grown under inducing (Lon+ or FtsH+) or depleting conditions (Lon+ or FtsH+, 60h of depletion for both, Lon and FtsH), and then exposed at 45°C during 0, 5, 10, 15 or 20 min. Then, growth after the heat treatment was monitored over time under inducing conditions by the 430/560 absorbance rate index that shows pH changes in the medium. The average from two independent biological replicates is shown for each condition.",
    "ncbi_link": "FtsH: 45596573
Lon: 45596210"
  },
  {
    "caption": "(C) In vivo degradation assays of FtsA, FtsZ and DnaB. ΔIndLon mutants expressing the different N-terminal FLAG-tagged derivatives were grown in depleting conditions for 36h. Then, Lon expression was transiently induced for 3h before translation was blocked with gentamicin (Gm). Samples were taken at the indicated time points after gentamicin treatment, and processed for immunoblot analysis using anti-FLAG antibodies. LC, loading control. As controls, non-induced cells were also treated with gentamicin and processed at the same time points. Immunoblots are representative of two independent experiments.",
    "ncbi_link": "FLAG: 
Lon: 45596210"
  },
  {
    "caption": "(I) Similar to panel C, but for FtsH candidate substrates. In this case, C-terminal FLAG-tagged derivatives were grown in depleting conditions for 60h before transient expression of FtsH for 3h and gentamicin treatment.",
    "ncbi_link": "FLAG: 
FtsH: 45596573"
  },
  {
    "caption": "(B) Protein stability assessment of Lon substrates containing multiple or single mutations in putative Lon degrons. N-terminal FLAG-tagged derivatives with mutations shown in panel A were expressed in the ΔIndLon mutant. Protein levels were then determined by immunoblot using anti-Lon and anti-FLAG antibodies comparing inducing (+) or depleting (-) conditions (48h of depletion). LC, loading control.",
    "ncbi_link": "Lon: 45596210"
  },
  {
    "caption": "(B) Lon surveillance of truncated protein variants. As an example, an N-terminal FLAG-tagged derivative of MPN304, which encodes a truncated variant of ArcA (ArcA-Nt), was expressed in the ΔIndLon mutant, and its accumulation monitored over time under non-inducing conditions using anti-FLAG antibodies. Anti-Lon antibodies were used to monitor Lon depletion along the time course experiment (western blot figure on left). MPN304 stability was also assessed by in vivo degradation experiments in Lon depleted mutants (36h of depletion), in which protein expression was blocked with gentamicin (Gm) during the indicated time points after transient induction of Lon for 3h. As control, samples after Gm treatment were also taken from non-induced samples. LC, loading control (western blot figure on right). Immunoblots are representative of two independent experiments. A schematic representation of the arginine deiminase pathway, which is inactive in M. pneumoniae, and the estimated protein copy number of its components are also shown for the ΔIndLon mutant grown in inducing (+) or depleting (-) conditions.",
    "ncbi_link": "MPN304: 
Lon: 45596210"
  },
  {
    "caption": "(E) Protein quality control of terminal organelle assembly mediated by Lon. Top of panel E, a schematic representation of the genetic organization at the P65 operon after deleting the N-terminal region of the hmw2 gene in the ΔIndLon mutant. The expected PCR products for the deletion are also indicated. Below, an agarose electrophoresis gel showing the PCR validation of the intended deletion, and SDS-PAGE and immunoblot analyses monitoring the expression of specific terminal organelle proteins, whose stability depend on HMW2, for ΔIndLon or ΔIndLon_Δhmw2Nt cell lysates grown in inducing (+) or depleting (-) conditions (48h of depletion). LC, loading control.",
    "ncbi_link": "hmw2: 45596187
HMW2: 45596187
Lon: 45596210"
  },
  {
    "caption": "16 days after tumor inoculation, B16F10 tumors from WT and Ythdf2 cKO mice were digested for flow cytometry analysis. D, Percentage (left) and absolute numbers (right) of CD8+ T cells in tumors (n=4). Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "16 days after tumor inoculation, B16F10 tumors from WT and Ythdf2 cKO mice were digested for flow cytometry analysis. E, Representative plots (left) and the percentage (right) of IFNγ producing CD8+ T cells (n=5). Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "16 days after tumor inoculation, B16F10 tumors from WT and Ythdf2 cKO mice were digested for flow cytometry analysis. G, Percentage (left) and absolute numbers (right) of Treg cells (n=4). Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "16 days after tumor inoculation, B16F10 tumors from WT and Ythdf2 cKO mice were digested for flow cytometry analysis. I, The proportion of Treg cells expressing the indicated surface marker (n=5). Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "splenocytes from 1-year-old WT and Ythdf2 cKO mice were analyzed by flow cytometry (n=4). C, Representative plots (left) and the percentage (right) of naïve (CD62LhiCD44lo), central memory (cMem, CD62LhiCD44hi), and effector memory (eMem, CD62LloCD44hi) T cells. Data are presented as means ± s.d. and were analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "splenocytes from 1-year-old WT and Ythdf2 cKO mice were analyzed by flow cytometry (n=4). D, Representative plot (left) of FOXP3 expression level and the FOXP3 expression MFI (right) in splenic Treg cells. Data are presented as means ± s.d. and were analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "splenocytes from 1-year-old WT and Ythdf2 cKO mice were analyzed by flow cytometry (n=4). E, Representative plots (left) and percentage (right) of FOXP3 expressing Treg cells in CD4 T cells. Data are presented as means ± s.d. and were analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "splenocytes from 1-year-old WT and Ythdf2 cKO mice were analyzed by flow cytometry (n=4). F, Representative plot (left) of FOXP3 Treg cells PD-1 expression and the MFI value (right) in WT and Ythdf2 cKO Treg cells. Data are presented as means ± s.d. and were analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "B, Functional assay with WT (n=5) or Ythdf2 cKO Treg (n=5) cells isolated from B16F10 tumors on day 16. B, Percentage of IFNγ producing CD8+ T cells after coculture. Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "G, Representative plots (left) and ratio (right) of GFP+/GFP- Treg cells in B16F10 tumors from Foxp3CreGFP/+Ythdf2fl/+ or Foxp3CreGFP/+Ythdf2fl/fl mice.",
    "ncbi_link": "GFP: 
Cre: 2777477
Foxp3: 20371
Ythdf2: 213541"
  },
  {
    "caption": "E, IGV visualization showing m6A and YTHDF2 binding at Nlrc3, Nfkbie, and Traf3 loci in CD4+ T cells (GSE188853).",
    "ncbi_link": "Nfkbie: 18037
Nlrc3: 268857
Traf3: 22031"
  },
  {
    "caption": "E, Relative mRNA levels of indicated genes in WT or Ythdf2 cKO Treg cells before or after 24 hours TNFα stimulation. Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "F, WT or Ythdf2 cKO Treg cells from the spleen were stimulated with 10 ng/mL TNFα in vitro. 24 hours post TNFα stimulation, cells were treated with Actinomycin D. Decay of Nlrc3, Nfkbie, and Traf3 was monitored by RT-qPCR (n=3, biological replicates). Data are presented as means ± s.d. and analyzed two-way ANOVA.",
    "ncbi_link": "Nfkbie: 18037
Nlrc3: 268857
Traf3: 22031
Ythdf2: 213541"
  },
  {
    "caption": "H, Functional assay with WT (n=4) or Ythdf2 cKO Treg (n=5) cells isolated from B16F10 tumors on day 16. H, Percentage of IFNγ producing CD8 T cells after coculture. Each data point represents one mouse. Data are presented as means ± s.d. and analyzed by two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ythdf2: 213541"
  },
  {
    "caption": "B Concentration-dependent avoidance of saponin in control, Gr28bMi and Gr28b Df/ Gr28bMi (n ≥ 4).",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "D, E PER assay for control and Gr28bMi flies in the (D) legs or (E) proboscis. Flies were initially given 2% sucrose, then 2% sucrose in combination with 5% saponin (n = 4). The error bars represent SEMs. The asterisks indicate significant differences from that of the control detected by a single-factor ANOVA with Scheffe's analysis as a post hoc test to compare two sets of data (*P < 0.05, **P < 0.01). ",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "A Mapping analysis of all the sensilla following stimulation with 5% saponin in control and Gr28bMi flies (we followed Tanimura's nomenclature) (n ≥ 8). The error bars represent SEMs. The asterisks indicate significant differences from that of the control detected by a single-factor ANOVA with Scheffe's analysis to compare two sets of data (*P < 0.05, **P < 0.01).",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "C Tip recording analysis of S6 sensilla from control and Gr28bMi flies. Stimuli used are 0.2% DEET, 1.0 mM coumarin, 0.5 mM quinine, 10 mM umbelliferone, 10 mM caffeine, 0.3 mM strychnine, 0.3 mM lobeline, 0.1 mM chloroquine, 0.2 mM denatonium, 0.5 mM papaverine, 0.1 mM berberine and 0.1% SDS (n ≥ 7). The error bars represent SEMs.",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "D Binary food choice assays were conducted after GRNs were ablated by expressing the cell death gene (hid), under Gr33a-GAL4 or Gr66a-GAL4. All heterozygote controls (UAS-hid/+, Gr33a-GAL4/+, and Gr66a-GAL4/+) are shown (n ≥ 4). The error bars represent SEMs. The asterisks indicate significant differences from that of the control detected by a single-factor ANOVA with Scheffe's analysis to compare two sets of data (*P < 0.05, **P < 0.01).",
    "ncbi_link": "GAL4: 855828
Gr33a: 34641
Gr66a: 38935
hid: 40009"
  },
  {
    "caption": "B RT-PCR analysis with the indicated primers in A for control and Gr28bMi flies with tubulin as a control. From left to right, the band of tubulin of wild-type, tubulin of Gr28bMi, DNA ladder, Gr28b of wild-type, and Gr28b of Gr28bMi.",
    "ncbi_link": "tubulin: 
Gr28b: 117496"
  },
  {
    "caption": "Each isoform from Gr28b.a to Gr28b.e was driven by Gr28b.a-GAL4 or Gr28b.c-GAL4 in a Gr28bMi background. The asterisks indicate significant differences from that of the Gr28b mutant detected by a single-factor ANOVA with Scheffe's analysis (**P < 0.01). C Binary food choice assay for recovery experiments with each of the five alternative Gr28b isoforms using the GAL4/UAS systems. (n ≥ 4).",
    "ncbi_link": "GAL4: 855828
Gr28b.a: 117496
Gr28b: 117496
Gr28b.c: 117496
Gr28b.e: 117496"
  },
  {
    "caption": "D Each isoform from Gr28b.a to Gr28b.e was driven by Gr28b.a-GAL4 or Gr28b.c-GAL4 in a Gr28bMi background. The asterisks indicate significant differences from that of the Gr28b mutant detected by a single-factor ANOVA with Scheffe's analysis (**P < 0.01). D Saponin-induced action potential frequencies from the indicated transgenic flies on S6 sensilla (n = 7).",
    "ncbi_link": "GAL4: 855828
Gr28b.a: 117496
Gr28b: 117496
Gr28b.c: 117496
Gr28b.e: 117496"
  },
  {
    "caption": "A Binary food choice assays were conducted after GRNs were ablated by expressing the cell death gene (hid), under Gr28b.c-GAL4 (n = 4).",
    "ncbi_link": "GAL4: 855828
Gr28b.c: 117496
hid: 40009"
  },
  {
    "caption": "A, B Survival rate of (A) control and (B) Gr28bMi adult raised on control and the indicated concentrations of saponin-containing cornmeal diet (n = 4).",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "C, D Survival rate based on binary food choice. control and Gr28bMi were allowed to feed 100 mM fructose versus 100 mM (C) or 200 mM fructose (D) mixed with 5% or 7.5% saponin.",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "E, F Cumulative pupation rate of (E) control and (F) Gr28bMi larvae raised on the indicated saponin-containing food as well as control food (n = 4). The error bars represent SEMs. The asterisks indicate significant differences from normal diet fed which were detected by a single-factor ANOVA with Scheffe's analysis (*P < 0.05, **P < 0.01).",
    "ncbi_link": "Gr28b: 117496"
  },
  {
    "caption": "C.  Western blot analysis of CTRL#1 or BRD9-KO#1 lysates from cells treated for the indicated  times  with 1000 IU/mL of IFN-α2. The indicated proteins were detected with specific antibodies. Data are representative of at least two biological replicates.",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "D. Immunofluorescence  analysis of CTRL#1 or  BRD9-KO#1 cells treated for the indicated  times  with 1000 IU/mL of IFN-α2. The indicated proteins were detected with specific antibodies. Data are representative of at least two biological replicates. Scale bars indicate 10μm.",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "F. Western blot  analysis of CTRL#1 or BRD9-KO#1 lysates from cells treated or not for 16h with 1000 IU/mL of IFN-α2. The indicated proteins were detected with specific antibodies. Data are representative of at least two biological replicates.",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "I. CTRL#1 or BRD9-KO#1 cells were stably-transduced with  BRD9-expressing, or control (EV, empty vector),  lentiviruses  and treated with 1000 IU/mL of IFN-α2  for 16h prior to infection with  IAV (WSN/33) at an MOI of 0.01 PFU/cell. Viral titers  were determined after 24h by  plaque assay. Data information: data represent means and standard deviations from n=3 biological experiments (individual data points shown). Statistical significance was determined by 1-way ANOVA on log-transformed plaque counts (**p-value < 0.001; ****p-value < 0.0001). Dotted lines are a visual guide for maximum and minimum virus replication in control cells in the absence and presence of  IFN-α2, respectively. Numbers above  IFN-α2-treated bars indicate their approximate difference to the respective untreated conditions.",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "F.  RT-qPCR confirmation of transcriptomics results for selected transcripts (MX1,  MX2, IFITM1, ISG15 and IFIT1) in A549 cells treated as outlined in (A). GAPDH transcript levels were used for normalization. Data represent means and standard deviations from n=3 biological experiments (individual data points shown). Statistical significance was determined by unpaired 2-tailed t-test on ΔCt values (*p-value < 0.05; n.s. not significant).",
    "ncbi_link": "GAPDH: 2597
IFIT1: 3434
IFITM1: 8519
ISG15: 9636
MX1: 4599
MX2: 4600"
  },
  {
    "caption": "G.  Western blot  analysis of CTRL#3 or BRD9-KO#3 cells stably transduced with lentiviruses expressing empty vector (EV), or wt and chimeric constructs",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "H.  Western blot  analysis of input lysates and anti-BRD9 immunoprecipitations (IPs) from cells described in (G) expressing wt BRD9 or the chimeric BRD7DUF. The indicated proteins were detected with specific antibodies. Data are representative of two biological replicates.",
    "ncbi_link": "BRD7: 29117
BRD9: 65980"
  },
  {
    "caption": "I. The various CTRL#3 or  BRD9-KO#3 cells described in (G) were stimulated and infected as described in (B). Data information: data represent means and standard deviations from n=3 biological experiments (individual data points shown). Numbers above IFN-α2-treated bars indicate their approximate difference to the respective untreated conditions. Dotted lines are a visual guide for minimum virus replication in control cells in the presence of IFN-α2. Statistical significance was determined by 1-way ANOVA on log-transformed intensity values (***p-value < 0.001; ****p-value < 0.0001; n.s. not significant).",
    "ncbi_link": "BRD9: 65980"
  },
  {
    "caption": "A) (left) t-sne plot from scRNAseq data of human organoids and cluster assignment of colonic cell populations. Red color corresponds to undifferentiated cells, light green corresponds to surface colonocytes (enterocytes). t-sne plot for selected genes from single cell RNAseq of human colon epithelial cells revealing expression of ACE2 specifically in differentiated surface colonocytes expressing KRT20 and AQP8, which also express the IFN-γ receptor IFNGR2. B) Immunofluorescence staining for ACE2 (red) and KRT20 (green) of human colon tissue section indicating ACE2 expression in surface colonocytes. Scale bar: 50 µm.",
    "ncbi_link": "ACE2: 59272
AQP8: 343
IFN-γ: 3458
IFNGR2: 3460
KRT20: 54474"
  },
  {
    "caption": "Comparison of E) KRT20, F) MUC2, G) CHGA, H) LGR5 mRNA expression in organoids grown in FM or in basic medium and either untreated or treated with IFN-γ (n=3). Data are presented as mean +/- SD ,*: p≤0.05, **: p≤0.001, ***: p≤0.0001, as determined by one-way ANOVA, followed by Tukey's multiple comparisons test",
    "ncbi_link": "CHGA: 1113
KRT20: 54474
LGR5: 8549
MUC2: 4583"
  },
  {
    "caption": "ACE2 mRNA expression in organoids grown in FM or in basic medium and either untreated or treated with IFN-γ (n=3). Data are presented as mean +/- SD ,*: p≤0.05, **: p≤0.001, ***: p≤0.0001, as determined by one-way ANOVA, followed by Tukey's multiple comparisons test",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "B) qPCR data displaying the relative virus load of SARS-CoV-2 measured by viral genome quantity in full medium vs. basic medium organoids 48 h after infection and normalized to GAPDH (n=6). C) qPCR data displaying the relative virus load of SARS-CoV-2 measured by viral genome quantity in full medium vs. full medium + IFN-γ treated organoids 48 h after infection and normalized to GAPDH (n=9). D) qPCR data displaying the relative virus load of SARS-CoV-2 measured by viral genome quantity in basic medium vs. basic medium + IFN-γ treated organoids 48 h after infection and normalized to GAPDH (n=4). E) qPCR data displaying the relative virus load of SARS-CoV-2 measured by viral genome quantity in full medium + IFN-γ vs. basic medium+ IFN-γ treated organoids 48 h after infection and normalized to GAPDH (n=4). (B-E) Data are presented as mean +/- SD ,*: p≤0.05, **: p≤0.001, ***: p≤0.0001, as determined by Student's t-test ",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "F) qPCR data comparing the relative virus load of SARS-CoV-2 measured by viral genome quantity normalized to GAPDH at 24 and 48 h after infection in full medium (left) and basic medium (right) untreated or treated with IFN-γ, indicating increase in virus load in differentiated and IFN-γ treated conditions (n=8). Data are presented as mean +/- SD ,*: p≤0.05, **: p≤0.001, ***: p≤0.0001, as determined by one-way ANOVA, followed by Tukey's multiple comparisons test",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "D) Relative expression of selected enterocyte-specific genes upon SARS-CoV-2 infection, normalized to GAPDH. Differences in gene expression were assessed using the linear model 'lmFit' and 'makeContrasts' in limma.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "F) qPCR data displaying the increase of INF-γ target genes (CXCL11, IFIT3) (upper) and enterocyte marker genes (KRT20, ACE2) (lower) after SARS-CoV-2 infection, validating the results from the microarray analysis (n=3). Data are presented as mean +/- SD ,****: p≤0.0001, as determined by Student's t-test",
    "ncbi_link": "ACE2: 59272
CXCL11: 6373
IFIT3: 3437
KRT20: 54474"
  },
  {
    "caption": "(c) Midguts from control Atg18KG03090/wild-type (Atg18/+), n = 14, and Atg18KG03090/Df(3L)6112 mutant (Atg18/Df), n = 11, animals at puparium formation analysed by differential interference contrast microscopy. Representative images are shown. (d) Wild-type, control (Atg18KG03090/+) and Atg18 mutant (Atg18/Df) midgut cell size quantification (μm2) at indicated stages; n = 10 animal intestines per genotype with 5 cells measured per intestine per stage.",
    "ncbi_link": "Atg18: 38913"
  },
  {
    "caption": "(e) Differential interference contrast images of midgut cells from Atg2EP3697/wild-type control (Atg2/+) and Atg2EP3697/Df(3L)6091 mutant (Atg2/Df) animals at puparium formation. Representative images are shown. (f) Cell size quantification (μm2) from e, n = 12 (Atg2/+) and n = 7 (Atg2/Df) animal intestines per genotype with 5 cells measured per intestine.",
    "ncbi_link": "Atg2: 38344"
  },
  {
    "caption": "(g-j) Representative TEM images of intestine cells 2 h after puparium formation. (g,i) Control Atg18KG03090/wild-type (Atg18/+, g) and control Atg2EP3697/wild-type (Atg2/+, i) cells with an enlarged image showing a double-membrane structure (arrowhead) that surrounds a mitochondrion and endoplasmic reticulum. Arrows indicate autolysosomes. (h,j) Atg18KG03090/Df(3L)6112mutant (Atg18/Df, h) and Atg2EP3697/Df (Atg2/Df, j) mutant cells lacking autophagic structures. Quantification is shown as mean ± s.d. Scale bars, 20 μm (a-c and e) and 1 μm (g-j).",
    "ncbi_link": "Atg18: 38913
Atg2: 38344"
  },
  {
    "caption": "(a) Midguts dissected from animals expressing Atg18IR specifically in DsRed-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast (DIC) microscopy. Representative images are shown. (b) Quantification (μm2) from a, n = 12 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg18: 38913"
  },
  {
    "caption": "(c) Midguts expressing mCherry-Atg8a in all cells, and expressing Atg18IR specifically in GFP-marked cell clones dissected from animals at 2 h after puparium formation. Representative images are shown.",
    "ncbi_link": "Atg18: 38913"
  },
  {
    "caption": "(d) Midguts dissected from animals at puparium formation that contain an Atg1Δ3D loss-of-function mutant cell clone (lacking GFP) and analysed by fluorescence and differential interference contrast microscopy. Wild-type (+/+) control cell possesses stronger GFP and heterozygous Atg1Δ3D/wild-type (Δ3D/+) cells have weaker GFP. Representative images are shown. (e) Quantification (μm2) from d, n = 7 (+/+), n = 8 (Δ3D/+) and n = 8 (Δ3D/Δ3D) animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "(f) Midguts dissected from animals expressing mCherry-Atg8a in all cells, and expressing Atg1IR specifically in GFP-marked clones of cells at 2 h after puparium formation. Representative images are shown.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "(g-j) Representative cut views from three-dimensional reconstitution images from wild-type (g,h) and Atg1 knockdown (i,j) cells at early third instar larval stage (g,i) and at puparium formation (h,j). (k) Quantification of cell volume (μm3) from g-j, n = 5 animal intestines per genotype with 1-5 cells measured per intestine per stage. Black columns: early third instar larval stage. White columns: puparium formation stage. Quantification is shown as mean ± s.d. NS, not significant. Scale bars, 20 μm.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "(a) Midguts dissected from animals at puparium formation that contain Vps34Δm22 loss-of-function mutant cell clones (lacking GFP) and analysed by fluorescence and differential interference contrast (DIC) microscopy. Wild-type (+/+) control cells possess stronger GFP and heterozygous Vps34Δm22/wild-type (Δm22/+) cells have weaker GFP. Representative images are shown. (b) Quantification (μm2) from a, n = 14 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Vps34: 37733"
  },
  {
    "caption": "(c) Midguts dissected from animals expressing Atg8aIR specifically in GFP-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast microscopy. Representative images are shown. (d) Cell size quantification (μm2) from c, n = 10 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(e) Midguts dissected from animals expressing Atg12IR specifically in DsRed-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast microscopy. Representative images are shown. (f) Cell size quantification (μm2) from e, n = 14 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg12: 39383"
  },
  {
    "caption": "(g-i) Midguts dissected from early third instar larvae that mis-express Atg1GS10797 (Atg1; g, GFP in nucleus and cytoplasm), both Atg1 +Atg8aIR (h), or both Atg1 +Atg7IR (i) and stained to detect Discs large (green) on the cortex of all cells. Representative images are shown. (g' and i') DIC images of midguts expressing mCherry-Atg8a in all cells, Atg1 (g'), and Atg1+Atg7IR (i') in GFP-marked clones of cells. mCherry-Atg8a puncta are shown in insets. Representative images are shown. Quantification is shown as mean ± s.d. Scale bars, 20 μm.",
    "ncbi_link": "Atg1: 39454
Atg7: 37141
Atg8a: 32001"
  },
  {
    "caption": "(a) Midguts dissected from animals at puparium formation that contain Atg7d4 loss-of-function mutant cell clones (lacking GFP) and analysed by fluorescence and differential interference contrast (DIC) microscopy. Wild-type (+/+) control cells possess stronger GFP and heterozygous Atg7d4/wild-type (d4/+) cells have weaker GFP. Representative images are shown. (b) Cell size quantification (μm2) from a, n = 8 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(c) Midguts expressing mCherry-Atg8a in all cells, and with Atg7d4 loss-of-function clone cells (lacking GFP) at 2 h after puparium formation. Representative images are shown.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(f) Midguts expressing GFP-Atg5 in enterocytes (larger nuclei) with an Atg7d4 loss-of-function clone cell (lacking RFP) at puparium formation. Representative images are shown.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(g,h) Representative TEM images of intestine cells 2 h after puparium formation. Arrows indicate autolysosomes. (g,h) Control (Atg7d30/d14; g) and Atg7 mutant (Atg7d77/d14; h) cells both contain autophagic structures. (h, right) Enlarged Atg7 mutant cell image of a double-membrane autophagosome (arrowhead) surrounding a mitochondrion. Quantification is shown as mean ± s.d. NS, not significant. Scale bars, 20 μm (a,c,d and f) and 1 μm (g,h).",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(a) Quantification of mitochondria numbers from Atg18 control (Atg18KG03090/wild type) and mutant (Atg18KG03090/Df(3L)6112) or Atg7 control (Atg7d30/d14) and mutant (Atg7d77/d14) TEM images. Mitochondria were quantified from 2 distinct 25 μm2 regions per cell from 2 cells per animal from at least 3 different animals per genotype.",
    "ncbi_link": "Atg18: 38913
Atg7: 37141"
  },
  {
    "caption": "(b,c) Midguts dissected from either early third instar larvae (b) or at puparium formation (c) that express GFP-labelled mitochondria in all cells and contain an Atg1Δ3D loss-of-function mutant cell clone (lacking RFP). Wild-type control cells possess stronger RFP and heterozygous cells have weaker RFP. Representative images are shown. Quantification is shown as mean ± s.d. NS, not significant. Scale bars, 0 μm.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "(a) Midguts dissected from animals expressing Uba1IR specifically in GFP-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast (DIC) microscopy. Representative images are shown. (b) Cell size quantification (μm2) from a; n = 16 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(c) Midguts dissected from animals at puparium formation that contain Uba1H33 loss-of-function mutant cell clones (lacking RFP) and analysed by fluorescence and differential interference contrast microscopy. Wild-type (+/+) control cells possess stronger RFP and heterozygous Uba1H33/wild-type (H33/+) cells have weaker RFP. Representative images are shown. (d) Quantification (μm2) from c, n = 8 (+/+), n = 11 (H33/+) and n = 11 (H33/H33) animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(e) Midguts dissected from animals at puparium formation that contain Uba1H33 loss-of-function MARCM mutant cell clones (GFP-positive) that also have mCherry-Atg8a expressed in all cells and analysed by fluorescence microscopy. Control wild-type and heterozygous cells have no GFP. Representative images are shown.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(f) Midguts expressing GFP-Atg5 in enterocytes (larger nuclei), and with an Uba1H33 loss-of-function clone cell (lacking RFP) at puparium formation analysed by fluorescence microscopy. Representative images are shown.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(g) Midguts dissected from animals at puparium formation that contain Uba1H33 loss-of-function MARCM mutant cell clones (GFP-positive) that are stained with p62 antibody and analysed by fluorescence microscopy. Control wild-type and heterozygous cells have no GFP. Representative images are shown.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(h) Midguts dissected from animals expressing Dts7, a dominant temperature-sensitive mutant of the β2 subunit of the proteasome, specifically in GFP-marked cells at puparium formation and analysed by fluorescence and differential interference contrast microscopy. Representative images are shown. (i) Cell size quantification (μm2) from h, n = 6 animal intestines per genotype with 1-5 cells measured per intestine. Quantification is shown as mean ± s.d. NS, not significant. Scale bars, 20 μm.",
    "ncbi_link": "Dts7: 39628"
  },
  {
    "caption": "(a,b) E1-charging assay for Uba1 and Atg7 with either Atg8a (a) or ubiquitin (Ub; b), n = 2 experiments with independently isolated proteins and analyses. Flag-tagged baculoviral-expressed E1s were incubated with either His-tagged Atg8a or Ub in the presence or absence of β-mercaptoethanol, separated by electrophoresis and blotted. Band shift was detected with anti-Flag antibody. Relative molecular mass (Mr K) ladders are indicated. Representative images are shown. Relative molecular masses: Flag-Uba1, 135K; Flag-Atg7, 81K; His-Atg8a, 29K; Ub, 9K.",
    "ncbi_link": "Atg7: 37141
Uba1: 35998"
  },
  {
    "caption": "(c) Midgut protein extracts at puparium formation from wild-type, Atg7 mutant (Atg7d77/d14) and Atg8 (Atg8KG07569) mutant animals blotted with anti-Atg8 and anti-Tubulin, n = 3 independent biological experiments. Representative images are shown.",
    "ncbi_link": "Atg7: 37141
Atg8: 32001"
  },
  {
    "caption": "(d) Midguts from control Atg310/wild-type (Atg3/+) and Atg310/Df(3L)cat mutant (Atg3/Df) animals at puparium formation analysed by differential interference contrast microscopy. Representative images are shown. (e) Cell size quantification (μm2) from d, n = 11 (Atg3/+) and n = 9 (Atg3/Df) animal intestines per genotype with 5 cells measured per intestine.",
    "ncbi_link": "Atg310: 40044
Atg3: 40044"
  },
  {
    "caption": "(f) Midguts dissected from early third instar larvae that mis-express Atg1GS10797 (Atg1) and Atg3IR only in the DsRed-marked cell clone and analysed by fluorescence and differential interference contrast (DIC) microscopy. Representative images are shown.",
    "ncbi_link": "Atg1: 39454
Atg3: 40044"
  },
  {
    "caption": "(g) Midguts dissected from animals expressing Atg4DN specifically in DsRed-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast microscopy. Representative images are shown. (h) Cell size quantification (μm2) from g, n = 10 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Atg4: 41868///33283"
  },
  {
    "caption": "(i) Midguts dissected from animals expressing mCherry-Atg8a in all cells, and expressing UbIR specifically in GFP-marked clones of cells at puparium formation. Representative images are shown.",
    "ncbi_link": "Ub: 326237///38456"
  },
  {
    "caption": "(j) Midguts dissected from animals expressing UbIR specifically in GFP-marked clones of cells at puparium formation and analysed by fluorescence and differential interference contrast microscopy. Representative images are shown. (k) Cell size quantification (μm2) from (j), n = 12 animal intestines per genotype with 1-5 cells measured per intestine.",
    "ncbi_link": "Ub: 326237///38456"
  },
  {
    "caption": "(l,m) Midguts dissected from early third instar larvae that exhibit Atg1GS10797 (Atg1) mis-expression in either a wild-type GFP-positive cell clone (l) or a Uba1H33 loss-of-function MARCM mutant cell clone (GFP-positive; m) and analysed by fluorescence and differential interference contrast microscopy. Control wild-type and heterozygous Uba1H33/wild-type cells have no GFP. Representative images are shown. (n) Quantification (μm2) from l and m, n = 22 (control), n = 16 (Atg1) and n = 6 (Atg1 +Uba1H33) animal intestines per genotype with 1-5 cells measured per intestine. Quantification data for control cells (l,m) were pooled because they are genetically identical. Quantification is shown as mean ± s.d. NS, not significant. Scale bars, 20 μm.",
    "ncbi_link": "Atg1: 39454
Uba1: 35998"
  },
  {
    "caption": "(a,b) Midguts dissected from either early third instar larvae (a) or at puparium formation (b) that express GFP-labelled mitochondria in enterocytes (larger nuclei) and contain Uba1H33 loss-of-function mutant cell clones (lacking RFP). Wild-type control cells possess stronger RFP and heterozygous cells have weaker RFP. Representative images are shown.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(c) Midguts dissected at puparium formation that express Uba1IR (GFP in nucleus and cytoplasm) and stained with ATP synthase complex V (ATPV) to detect mitochondria in all cells. Representative images are shown.",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "(d-f) Representative immuno-TEM images of Uba1IRclone cells at puparium formation. Uba1IR-expressing cells possess gold particles; control cells lack gold particles (d). Control cells possess numerous autolysosomes in the cytoplasm (arrowheads) and few mitochondria (asterisks); Uba1IR-expressing cells possess numerous mitochondria and few autophagic structures. Scale bars, 20 μm (a-c) and 1 μm (d-f).",
    "ncbi_link": "Uba1: 35998"
  },
  {
    "caption": "3D-brain model, horizontal brain section illustrating transgenic human P301Ltau expression in the entorhinal cortex (green, EC) of the ECrTgTaumouse lines, and the propagation of transgenic tau to the dentate gyrus (DG). Tau composition in ECrTgTau and control mouse lines investigated.",
    "ncbi_link": "tau: 4137
Tau: 4137
Tau: 17762"
  },
  {
    "caption": "Immunostained horizontal sections show the expression of human P301Ltau in ECneurons in absence of endogenous mousetau (ECrTgTau-Mapt0/0). Fluorescence in situ hybridization of humantau mRNA combined with immunofluorescent labeling (Immuno-FISH) of humantau protein (huTau) verifies P301Ltau transgene expression in the EC. Scale bars 50 μm.",
    "ncbi_link": "Mapt: 17762
tau: 4137
Tau: 4137
tau: 17762///4137"
  },
  {
    "caption": "Propagation of humantau protein to neurons in the DG (white arrows) in ECrTgTau-Mapt0/0 mice. Close-ups show DG neurons from three ECrTgTau-Mapt0/0 mice (DG I-III). Immuno-FISH proofs the absence of humantau expression in DG neurons, which have huTau protein but no humantau mRNA. Scale bars 50 μm.",
    "ncbi_link": "Mapt: 17762
Tau: 4137
tau: 4137
Tau: 17762"
  },
  {
    "caption": "Immunostained horizontal sections of ECrTgTaumice show the expression of human P301Ltau in ECneurons in presence of endogenous mousetau. Close-ups show DGneurons from three ECrTgTaumice (DG I-III) and Immuno-FISH proofs the absence of humantau expression in these DGneurons. Scale bars 50 μm.",
    "ncbi_link": "tau: 4137
Tau: 4137
tau: 17762///4137"
  },
  {
    "caption": "Human P301Ltau propagation to DG neurons (white arrows) in presence of endogenous mouse tau in ECrTgTau mice. Scale bars 50 µm.",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "Human (huTau, antibody Tau13) and total tau (hu+moTau, DAKO) levels in entorhinal cortex (EC) extracts from 18-month-oldmice show equal human P301Ltau expression in ECrTgTau and ECrTgTau-Mapt0/0 mice (p=0.201, n=3 mice/group, one-way ANOVA with Bonferroni correction)",
    "ncbi_link": "Mapt: 17762
Tau: 4137"
  },
  {
    "caption": "The number of human tau-positive cell bodies in the DG (p=0.58, n=4 sections and 3 mice/group) and human tau in hippocampal (HPC) extracts (p=0.14, n=3 mice/group) were similar in ECrTgTau-Mapt0/0 and ECrTgTau mice (two-tailed Student's T-test).",
    "ncbi_link": "Mapt: 17762
Tau: 4137"
  },
  {
    "caption": "Primary cortical neuron cultures that were transduced with AAVeGFP-2a-P301Ltau at 7 DIV, and fixed and immunostained for GFP and humantau (Tau13 antibody) at 14 DIV, show tau donor (GFP+, huTau+; ~10% neurons) and a small number of tau recipient neurons (GFP-, huTau+; ~1% neurons). Western blot of whole cell lysates verified efficient cleavage (~95%) of eGFP and P301Ltau by the 2a peptide (n=3).",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "Eight weeks after AAV injection into right EC of aged Mapt0/0 mice (=3), immunostained brain sections showed that huTauP301L (red) propagated to a few DG \"recipient neurons\" (white arrows). Scale bar 50 µm.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "Unilateral AAV-mediated human P301L tau expression in the EC and DG of age-matched WT mice (n=3). Representative images of brain sections show donor neurons in the injected EC and DG, and a few tau recipient neurons (white arrows) adjacent to the AAV injection site. Scale bar 50 µm.In the contralateral hemisphere of the same brain section, some tau recipient neurons (white arrows) were also present in the (non-injected) axonal projection areas in the contralateral EC (GFP-filled terminal ends). Scale bar 100 µm.",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "A. Brain sections from 18-month-old ECrTgTau-Mapt0/0 and ECrTgTau mice were co-immuolabeled for human tau and misfolded tau (Alz50). Misfolded tau was only found in EC and DG neurons (white arrows) of ECrTgTau but not ECrTgTau-Mapt0/0 animals (n=4 sections/mouse, 3 mice/group). Scale bars 50 μm.",
    "ncbi_link": "Mapt: 17762
Tau: 4137"
  },
  {
    "caption": "B+C. Immunofluorescence labeling and stereological counting of microglia in entorhinal cortex (B) and astrocytes in hippocampus (C) indicated early signs of neurodegeneration in ECrTgTaumice. The significantly increased number of Iba1-positive microglia in the EC layer II/III of ECrTgtau mice (compared to WT) was partially rescued in ECrTgTau-Mapt0/0 mice (non-significant). The number of GFAP-positive astrocytes was similar across all genotypes (non-significant). Mean±SEM, n=4 sections per mouse, 3 mice/group, one-way ANOVA with Bonferroni correction. Scale bars 100 μm.",
    "ncbi_link": "Mapt: 17762
Tau: 17762///4137"
  },
  {
    "caption": "Human, mouse and total tau protein levels in cortical TBS-extracts of rTg4510, rTg4510-Mapt0/0, and control mice: The amount of human tau (Tau13 antibody) was comparable in rTg4510 and rTg4510-Mapt0/0, moTau (Tau/5) was comparable in WT and rTg4510, and total tau levels (hu+moTau, DAKO antibody) were (expected) highest in rTg4510 mice. Mean±SEM, n=3 mice/group, non-significant.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "Whole brain weights of 9-month-old animals revealed pronounced brain matter loss in rTg4510 compared to WT mice (weight loss >16%), which was rescued in rTg4510-Mapt0/0 mice to >96%. Mean±SEM, n=5 mice/group.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "Cortical thickness measured adjacent to HPC, from CTX surface to corpus callosum, was decreased in rTg4510 mice by ≈25% compared to WT mice. rTg4510-Mapt0/0 showed no CTX thinning compared to Mapt0/0 or WT mcie. Mean±SEM, n=3 mice/group.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "The number of neurons (NeuN+ cells) in the cortex of rTg4510 mice was significantly reduced to ≈67% compared to both WT and rTg4510-Mapt0/0. Mean±SEM, n=3 mice/group.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "The volume of hippocampal region CA1, with CT the most effected regions in rTg4510 mice, was significantly reduced in rTg4510 by ~70% volume; rTg4510-Mapt0/0 had significantly larger CA1 volume left (reduced by only ~40%). Mean±SEM, n=3 mice/group.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "rTg4510 showed strong signs of neuroinflammation with extremely high numbers of activated astroglia (GFAP+, red) and microglia (Iba1+, white) in the CTX compared to WT mice. Both astro- and microgliosis was reduced by ~50% in rTg4510-Mapt0/0 mice. Mean±SEM, n=3 sections/mouse and 5 mice per/group. For all panels: two-tailed Student's T-test and one-way ANOVA with Bonferroni for multiple comparison, ns not significant, scale bars 100 µm.",
    "ncbi_link": "Mapt: 17762"
  },
  {
    "caption": "Cortical extracts from rTg4510-Mapt0/0 brains had significantly less phospho-tau (CP13, PHF1, 12E8) than rTg4510 extracts. Compared to WT mice, both transgenic tau lines had high levels of phospho-tau. Mean±SEM, n=3 mice/group.",
    "ncbi_link": "Mapt: 17762
tau: 4137"
  },
  {
    "caption": "Representative images of gallyas silver stained aggregated tau in cortices from 12-month-old mice unravel stunning differences in the degree of tau pathology in rTg4510 compared to rTg4510-Mapt0/0 mice. Mean±SEM, n=3 mice/group.",
    "ncbi_link": "Mapt: 17762
tau: 4137///17762"
  },
  {
    "caption": "Higher magnification images of silver (12 month-old) and Thioflavine-S (9month-old) stained cortices show mature tangles (white arrows in Thio-S stain) in rTg4510 and rTg4510-Mapt0/0 mice; enhanced pathological changes such as neuritic tau accumulation and neuropil vacuolation around NFTs are found only in rTg4510 mice. Stereological counting revealed similar numbers of cortical NFTs between in rTg4510 and rTg4510-Mapt0/0 mice at 9 and 12 month of age. Because of the pronounced neuronal death only in rTg4510 mice, the percentage of tangle-bearing neurons was ≈1.6 to 1.8-fold higher higher in 9 and 12-month old rTg4510 mice. Mean±SEM, n=3 sections/mouse, 3 mice/group.",
    "ncbi_link": "Mapt: 17762
tau: 4137"
  },
  {
    "caption": "Immuno-FISH for huTau mRNA (green) and phospho-tau (PHF1, red) shows obvious differences in the distribution of neurons in cortex layer II/III: 9-month-old rTg4510 mice had more neurons filled with NFT-like phosphorylated tau (PHF1+, red), and rTg4510-Mapt0/0 mice had significantly more huTau mRNA positive neurons (FISH+). rTg4510-Mapt0/0 mice had also more neurons still expressing both PHF1 and huTau mRNA (PHF1+ FISH+), suggesting a reduced neurotoxicity of P301Ltau expression in rTg4510-Mapt0/0 mice. Mean±SEM, n=3 sections per mouse, 3 mice/group. For all panels: two-tailed Student's T-test and one-way ANOVA with Bonferroni for multiple comparison, ns not significant, scale bars 100 μm.",
    "ncbi_link": "Mapt: 17762
Tau: 4137"
  },
  {
    "caption": "Immuno-FISH showing EC neurons having both misfolded somatic tau (Alz50, red) and human tau mRNA (green; white arrows) in rTg4510-Mapt0/0 but rarely in rTg4510 mice. n=3 sections, 2 mice/group. Scale bars 50 μm.",
    "ncbi_link": "Mapt: 17762
tau: 4137///17762"
  },
  {
    "caption": "Extraction of cortices revealed similar human tau (Tau13) in TBS-extracts (not significant) but significantly more human tau in TritonX-100 (TX-100) extracts of rTg4510-Mapt0/0 compared to rTg4510 mice. Mean±SEM, n =3 mice/group, two-tailed Student's T test, ns non significant.",
    "ncbi_link": "Mapt: 17762
tau: 4137///17762"
  },
  {
    "caption": "Native gel electrophoresis of cortical TBS-extracts showed small differences in HMW (oligomeric) human tau between rTg4510 and rTg4510-Mapt0/0 brains. Western blot lanes were averaged across ~2/3 of the width (black rectangular and arrow in Tau13 blot). The mean±SEM (n=3 mice/group) of these averages was plotted as longitudinal lane profiles. Differences in HMW tau are indicated by red and black arrows.",
    "ncbi_link": "Mapt: 17762
tau: 4137"
  },
  {
    "caption": "TBS-brain extracts were applied to a HEK293 cell tau aggregation seeding assay(Holmes et al, 2014, Sanders et al, 2014), in which TauRDP301S-CFP and TauRDP301S-YFP are co-expressed intracellularly. The formation of intracellular fluorescent TauRDP301S aggregates leads to Foerster resonance energy transfer (FRET) activity between co-aggregated CFP and YFP-tags and correlates with the tau aggregation seeding activity of the applied brain extracts. After 24 hours, cells treated with extract (0.5 µg and 1.0 µg total protein per 96 well) from 9-month-old rTg4510 had significantly more intracellular YFP-positive (white arrows) aggregates compared to rTg4510-Mapt0/0 extracts; FRET activity of TauRDP301S aggregates appeared similar for both rTg4510 and rTg4510-Mapt0/0. WT and Mapt0/0 extracts never showed seeding activity. Addition of lipofectamine corrected for differences in cellular uptake of tau and led to similar differences in seeding activity between rTg4510 and rTg4510-Mapt0/0 mice. Two-tailed Student's T-test, mean±SEM ns, not significant, Insets 100 µm, Scale bars 50 µm.",
    "ncbi_link": "Mapt: 17762
Tau: 4137"
  },
  {
    "caption": " A MMS-induced checkpoint activation is not altered in irc5-Δ1 cells. The level of Rad53 phosphorylation was analyzed in wild type (W303-1a) and irc5-Δ1 (IL012) cells by Western blot with an anti-Rad53 antibody ",
    "ncbi_link": "irc5: 850599"
  },
  {
    "caption": " B Prolonged checkpoint activation in irc5-Δ1 cells during recovery from MMS treatment. Rad53 phosphorylation status was analyzed in wild type (W303-1a) and irc5-Δ1 (IL012) cells by Western blot with an anti-Rad53 antibody; M, MMS ",
    "ncbi_link": "irc5: 850599"
  },
  {
    "caption": " C Lack of Irc5 results in an elevated number of cells with Rad52-YFP foci. At indicated time points samples of wild type (W3749-14C) and irc5-Δ1 (TB039) cells were collected, washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=5). Unpaired t-test was used to calculate the P-value. Representative microscopic photos of cells are shown. Scale bars: 5 μm ",
    "ncbi_link": "irc5: 850599
Irc5: 850599"
  },
  {
    "caption": " D Disruption of IRC5 leads to accumulation of ssDNA-containing lesions. ChEC analysis of wild type (BYR52MN) and irc5-Δ1 (TB040) cells cultured in the presence or absence of 0.03% MMS for 2 hours (n=3) ",
    "ncbi_link": "irc5: 850599
IRC5: 850599"
  },
  {
    "caption": "F Increased levels of bright Rfa1-YFP foci in cells lacking Irc5. At indicated time points culture samples of wild type (W3775-12C) and irc5-Δ1 (TB041) cells were collected, washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=5). Unpaired t-test was used to calculate the P-value. Representative microscopic photos of cells are shown. Scale bars: 5 μm",
    "ncbi_link": "Irc5: 850599
irc5: 850599"
  },
  {
    "caption": " A The irc5-Δ1 mutant exhibits S-phase delay in the presence of MMS. DNA content of wild type (W303-1a) and irc5-Δ1 (IL012) cells was measured by FACS and plotted as histograms ",
    "ncbi_link": "irc5: 850599"
  },
  {
    "caption": " B Completion of DNA replication is delayed in the irc5-Δ1 mutant after MMS treatment. Intact chromosomes were isolated from wild type (W303-1a) and irc5-Δ1 (IL012) cells and processed for PFGE. M, 0.03% MMS ",
    "ncbi_link": "irc5: 850599"
  },
  {
    "caption": " A Lack of Irc5 translocase activity results in elevated number of cells with Rfa1-YFP foci. At indicated time points samples of wild type (TB042) and irc5DAEA (TB043) cells were collected, washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=5). Unpaired t-test was used to calculate the P-value",
    "ncbi_link": "irc5: 850599
Irc5: 850599"
  },
  {
    "caption": " B Increased levels of bright Rad52-YFP foci in cells expressing Irc5DAEA lacking ATPase activity. At indicated time points samples of wild type (TB044) and irc5DAEA (TB045) cells were collected, washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=5). Unpaired t-test was used to calculate the P-value",
    "ncbi_link": "Irc5: 850599
irc5: 850599"
  },
  {
    "caption": "C Translocase activity of Irc5 is important for completion of DNA replication after MMS treatment. PFGE was performed as in Fig 2B using wild type (EMD09) and irc5DAEA (EMD10) strains",
    "ncbi_link": "Irc5: 850599
irc5: 850599"
  },
  {
    "caption": " A, B ChIP-qPCR analysis of Scc1 association with early replication origin ARS305 or ARS607. PK-tagged Scc1 interaction with chromatin was monitored in wild type (JC1513) and irc5Δ-1 (TB064) cells. Error bars represent mean value ± standard deviations of mean (n=3). ARS305 + 7 kb locus was used as a control for cohesin-free chromosomal region. POA1 was used as a control locus for the chromosomal region that is bound by cohesin but is located ~ 30.000 bp from the nearest replication origin ",
    "ncbi_link": "ARS305: 
POA1: 
irc5: 850599"
  },
  {
    "caption": " C, D ChIP-qPCR analysis of Pol2 association with early replication origin ARS305 or ARS607 as well as late replication origin ARS501. HA-tagged Pol2 interaction with chromatin was monitored in wild type (TB065) and irc5Δ-1 (TB066) cells. Error bars represent mean value ± standard deviations of mean (n=3)",
    "ncbi_link": "ARS305: 
ARS501: 
ARS607: 
irc5: 850599"
  },
  {
    "caption": " A, B ChIP-qPCR analysis of Scc1 association with early replication origin ARS305 or ARS607. HA-tagged Scc1 interaction with chromatin was monitored in wild type (Y39) and scc2-4 (Y4366) cells. Error bars represent mean value ± standard deviations of mean (n=3) ",
    "ncbi_link": "ARS305: 
ARS607: 
scc2: 851761"
  },
  {
    "caption": "C, D ChIP-qPCR analysis of Pol2 association with early replication origin ARS305 or ARS607. HA-tagged Pol2 interaction with chromatin was monitored in wild type (TB067) and scc2-4 (TB068) cells. Error bars represent mean value ± standard deviations of mean (n=3)",
    "ncbi_link": "ARS305: 
ARS607: 
scc2: 851761"
  },
  {
    "caption": "A Sensitivity of scc2-4 and scc2-4 irc5-Δ1 mutants to DNA damaging agents at permissive temperature 25°C. Logarithmically growing cultures of wild type (W303-1a), irc5-Δ1 (IL012), scc2-4 (TB069) and irc5-Δ1 scc2-4 (TB070) strains were 10-fold serially diluted and plated onto solid YPD containing indicated concentrations of DNA damaging agents",
    "ncbi_link": "irc5: 850599
scc2: 851761"
  },
  {
    "caption": "B, C Levels of DNA repair foci in scc2-4 and scc2-4 irc5-Δ1 mutants. Logarithmically growing cultures of scc2-4 (TB071 or TB073) and scc2-4 irc5-Δ1 (TB072 or TB074) were treated with MMS for 1 hour at 25°C. Next, cells were washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=3)",
    "ncbi_link": "irc5: 850599
scc2: 851761"
  },
  {
    "caption": "D Sensitivity of scc1-73 and scc1-73 irc5-Δ1 mutants to DNA damaging agents at permissive temperature 25°C or semi-permissive temperature  30°C. Logarithmically growing cultures of wild type (W303-1a), irc5-Δ1 (IL012), scc1-73 (JC1339) and irc5-Δ1 scc1-73 (TB075) strains were 10-fold serially diluted and plated onto solid YPD containing indicated concentrations of DNA damaging agents",
    "ncbi_link": "irc5: 
scc1: "
  },
  {
    "caption": "E, F Levels of Rfa1-YFP and Rad52-YFP foci in scc1-73 and irc5-Δ1 scc1-73 mutants. Logarithmically growing cultures of scc1-73 (TB076 or TB078) and irc5-Δ1 scc1-73 (TB077 or TB079) were treated with MMS for 1 hour at  25°C. Next, cells were washed and processed for microscopic analysis. Error bars represent mean value ± standard deviations of mean (n=3)",
    "ncbi_link": "irc5: 850599
scc1: 851561"
  },
  {
    "caption": "G Replication completion defect of scc1-73 is not exacerbated by IRC5 disruption. Intact chromosomes were isolated from scc1-73 (JC1339) and irc5-Δ1 scc1-73 cells (TB075), cultured at 25°C, and processed for PFGE. M, 0.03% MMS",
    "ncbi_link": "IRC5: 850599
irc5: 850599
scc1: 851561"
  },
  {
    "caption": "A Manhattan plot displaying the GWAS results of Na+/K+ ratio in root. The red-dashed line indicates the Bonferroni-adjusted significance threshold (P = 1.0 × 10-7). Red arrow indicates the significant SNP signal of Na+/K+ ratio associated with SlHAK20.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "B The nucleotide diversity ratios between PIM and CER, and between CER and BIG on chromosome 4. The black-dashed horizontal lines indicate top 10% threshold for entire chromosome 4 (1.82 πPIM/πCER for domestication and 4.27 πCER/πBIG for improvement). The red arrows indicate the position of SlHAK20 in the sweeps. π, nucleotide diversity.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "C SlHAK20-based association mapping and pairwise LD analysis. Dots represent SNPs. Indel48 is highlighted in red. The indel-2381, indel-1818 in the promoter region and five nonsynonymous variants are marked in blue. These eight variants are related to the pairwise LD diagram with dashed lines.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "D Haplotypes of SlHAK20 among tomato natural variations. The distribution of Na+/K+ ratio in each haplotype group is exhibited by a box plot. The n indicates the number of accessions belonging to each haplotype. In the box plots, the middle line indicates the median, the box indicates the range of the percentiles of the total data using Turkey method, the whiskers indicate the interquartile range and the outer dots are outliers. Significant difference was determined by Student's t-test.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "E Allele distribution of the SlHAK20 locus at position in PIM, CER, and BIG groups. The n indicates the accession number.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "The expression pattern of SlHAK20 in tomato. The GUS activity was examined in seedling (left) and root (right) of 21-days-old SlHAK20TS-21pro:GUS transgenic tomato (B). Bars, 2 cm.",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "The expression pattern of SlHAK20 in tomato. Cross-sections of hypocotyl (C) of SlHAK20TS-21pro:GUS transgenic plants. The scale bar is 400 μm in (C)",
    "ncbi_link": "SlHAK20: 101256474"
  },
  {
    "caption": "E Subcellular localization of SlHAK20-YFP in tomato. The SlHAK20Hap1-YFP (left) and SlHAK20Hap2-YFP (right) were localized in the plasma membrane. YFP, yellow florescence protein. FM4-64, a lipophilic styryl compound as a red fluorescent marker of plasma membrane. Bar, 20 μm.",
    "ncbi_link": "SlHAK20: 
SlHAK20: 101256474"
  },
  {
    "caption": "F SlHAK20 complements the K+ uptake-defective yeast mutant assayed using a dose-response method. The K+ uptake-defective yeast mutant R5421 transformed with SlHAK20Hap1, SlHAK20Hap2, and vector (p416-GPD) were cultured in AP medium containing indicated concentrations of K+ for 24 h. The data points represent three replicates.",
    "ncbi_link": "SlHAK20: 
SlHAK20: 101256474"
  },
  {
    "caption": "G Na+ uptake analysis of yeast cells expressing SlHAK20. Shown are the Na+ concentrations in the medium over the time of culture of the ANT3 yeast cells transformed with SlHAK20Hap1, SlHAK20Hap2, or empty vector. The initial NaCl concentration in the medium was 60 μM. The data are shown as the means ± SD (n = 4).",
    "ncbi_link": "SlHAK20: 
SlHAK20: 101256474"
  },
  {
    "caption": "H Na+ uptake kinetic analysis of SlHAK20 in yeast cells. The curves show concentration- dependent Na+ influx in yeast expressing SlHAK20Hap1 or SlHAK20Hap2 in the presence of 0, 5, 10, 20, 30, 40, 50, 60, 100, 150 or 200 μM NaCl in the medium. The data are expressed as mean ± SD (n = 3).",
    "ncbi_link": "SlHAK20: 
SlHAK20: 101256474"
  },
  {
    "caption": "Na+/K+ ratio contents in roots of TS-21 wild type and slhak20 mutants. Data are shown as means ± SD (n = 4).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "Na+ contents in roots of TS-21 wild type and slhak20 mutants. Data are shown as means ± SD (n = 4).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "K+ contents in roots of TS-21 wild type and slhak20 mutants. Data are shown as means ± SD (n = 4).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "Na+ contents in the xylem sap of TS-21 and slhak20 mutants after 50 mM NaCl treatment for the indicated days. Data represent means ± SD (n = 4).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "K+ contents in the xylem sap of TS-21 and slhak20 mutants after 50 mM NaCl treatment for the indicated days. Data represent means ± SD (n = 4).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "G Shoot height of TS-21, slhak20-1, and slhak20-2. Plant height of 24-day-old TS-21, slhak20-1, and slhak20-2 were measured after growing under normal conditions for 14 days, followed by salt treatment for 14 days, and recovery for 10 days. Values are means ± SD (n = 10 plants of each genotype).",
    "ncbi_link": "slhak20: "
  },
  {
    "caption": "H Salt resistance of TS-21 wild type and slhak20 mutants. TS-21, slhak20-1, and slhak20-2 grown under normal growth conditions for 24 days, followed by a treatment with 200 mM NaCl for 14 days, and then recovered for 10 days. Control plants grown under normal growth conditions for 38 days. Scale bars, 5 cm.",
    "ncbi_link": "slhak20: 101256474"
  },
  {
    "caption": " Salt-tolerance assay of TS-670 and slhak20 mutant plants. TS-670, slhak20-3, and slhak20-4 grown under normal growth conditions for 23 days, and then treated with 150 mM NaCl for 5 days. Control plants grown under normal growth conditions for 28 days. ",
    "ncbi_link": "slhak20: 101256474"
  },
  {
    "caption": " Plant height and fresh weight of TS-670, slhak20-3, and slhak20-4 under normal and salt stress conditions. Shoot height f 23-day-old TS-670, slhak20-3, and slhak20-4 were quantified after growing under normal conditions for 5 days, or salt treatment with 150 mM NaCl for 5 days. Values are means ± SD (n = 10 plants of each genotype).",
    "ncbi_link": "slhak20: 101256474"
  },
  {
    "caption": " Plant height and fresh weight of TS-670, slhak20-3, and slhak20-4 under normal and salt stress conditions. resh weight f 23-day-old TS-670, slhak20-3, and slhak20-4 were quantified after growing under normal conditions for 5 days, or salt treatment with 150 mM NaCl for 5 days. Values are means ± SD (n = 10 plants of each genotype). ",
    "ncbi_link": "slhak20: 101256474"
  },
  {
    "caption": " Phenotype of NIP and oshak4/17 double mutant plants under normal and salt stress conditions. 20-day-old seedlings of NIP and oshak4/17 mutants were treated with 100 mM NaCl for 8 days. The pictures show representative plants ere analyzed among these genotypes. ontrol plants were grown under normal growth conditions for 28 days ",
    "ncbi_link": "oshak4: 4345789"
  },
  {
    "caption": " Phenotype of NIP and oshak4/17 double mutant plants under normal and salt stress conditions. 20-day-old seedlings of NIP and oshak4/17 mutants were treated with 100 mM NaCl for 8 days. The pictures show representative fresh weight of shoots were analyzed among these genotypes. Control plants were grown under normal growth conditions for 28 days and the fresh weights of shoots were measured. Values are means ± SD (n = 12 plants of each genotype for fresh weight ",
    "ncbi_link": "oshak4: 4345789"
  },
  {
    "caption": " Phenotype of NIP and oshak4/17 double mutant plants under normal and salt stress conditions. 20-day-old seedlings of NIP and oshak4/17 mutants were treated with 100 mM NaCl for 8 days. The pictures show representative survival rate were analyzed among these genotypes. ",
    "ncbi_link": "oshak4: 4345789"
  },
  {
    "caption": "A The transcript levels of SlHAK20 in TS-670 and three independent SlHAK20Hap1-YFP transgenic lines grown under normal growth conditions.",
    "ncbi_link": "YFP: 
SlHAK20: 101256474"
  },
  {
    "caption": "The Na+ in shoots and roots of TS-670 and three independent SlHAK20Hap1-YFP transgenic lines during salt stress. The 21-day-old TS-670, Hap1OE-1, Hap1OE-2 and Hap1OE-3 plants grown in 0.25× Hoagland which were then treated with 50 mM NaCl for additional 0 and 7 days.",
    "ncbi_link": "YFP: 
SlHAK20: 101256474"
  },
  {
    "caption": "The K+ in shoots and roots of TS-670 and three independent SlHAK20Hap1-YFP transgenic lines during salt stress. The 21-day-old TS-670, Hap1OE-1, Hap1OE-2 and Hap1OE-3 plants grown in 0.25× Hoagland which were then treated with 50 mM NaCl for additional 0 and 7 days.",
    "ncbi_link": "YFP: 
SlHAK20: 101256474"
  },
  {
    "caption": "The Na+/K+ ratio in shoots and roots of TS-670 and three independent SlHAK20Hap1-YFP transgenic lines during salt stress. The 21-day-old TS-670, Hap1OE-1, Hap1OE-2 and Hap1OE-3 plants grown in 0.25× Hoagland which were then treated with 50 mM NaCl for additional 0 and 7 days.",
    "ncbi_link": "YFP: 
SlHAK20: 101256474"
  },
  {
    "caption": "Formalin-fixed paraffin-embedded (FFPE) sections from control or Tgif1KO mice were immunostained with anti-pSmad2 antibody and revealed by immunofluorescence (IF) and DAPI. Representative pictures at 40x are shown (n=30). Scale bars, 100 μM.",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "FFPE pancreatic sections from control or Tgif1KO mice were stained with hematoxylin and eosin (H&E) or immunostained with antibodies to CK19 or Amylase and revealed by IHC. Representative pictures at 20x are shown (n=30). Scale bars, 200 μM.",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "Kaplan-Meyer survival analysis of control, Tgif1KO, KC and KTC mice. A regular mosaic two-colors line was used to discriminate between control and Tgif1KO mice.",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "Pictures of whole pancreas and spleen tissues from control, Tgif1KO, KC or KTC mice (left). Weight of pancreas was measured and presented as dot plot (n=30).",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "FFPE pancreatic sections from control, Tgif1KO, KC or KTC were stained with H&E or subjected to IHC analysis using antibodies to CK19 or α-SMA. Yellow arrows indicate PanINs in KC mice. Representative pictures at 20x are shown (n=30). Scale bars, 200 μM.",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "Tumor volume and metastasis in live KCLuc and KTCLuc mice were analyzed by IVIS bioluminescence. Following imaging live animals, pancreas, brain, liver and lung were dissected and analyzed again by IVIS bioluminescence (n= 6, 5 out of 6 mice developed metastasis to liver and lung).",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Expression of JunB in pancreas from control, KC or KTC mice (same as in D) was analyzed by qRT-PCR (n=6). Data are expressed as mean ± SEM. **p< 0.01; based on a two-tailed Student's test.",
    "ncbi_link": "JunB: 16477"
  },
  {
    "caption": "Protein extracts from MIAPaCa-2 cells (left) and control or Tgif1KO mice (right) were immunoprecipitated using normal IgG, anti-TGIF1 or anti-Twist1 antibody and analyzed by immunoblotting using antibodies to Twist1 or TGIF1 (A-C).",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "Protein extracts from control or Tgif1KO mice (right) were immunoprecipitated using normal IgG, anti-TGIF1 or anti-Twist1 antibody and analyzed by immunoblotting using antibodies to Twist1 or TGIF1 To control for loading, total cell lysates were analyzed by immunoblotting using antibodies to Twist1, TGIF1 or β-Actin.",
    "ncbi_link": "Tgif1: 21815"
  },
  {
    "caption": "PL45 stably expressing Dox-inducible control or sh-RNA targeting TGIF were treated with vehicle or Dox for 48 hr and analyzed for Twist1 expression by immunoblotting or qRT-PCR (n=6). In left panel, the intensity of the bands was assessed by densitometry, and the result was presented as a ratio of Twist1/TGIF1.",
    "ncbi_link": "TGIF: 7050"
  },
  {
    "caption": "PL45 stably expressing Dox-inducible TGIF1 were treated with vehicle or Dox for 48 hr and analyzed for binding of TGIF1 to the Twist1 promoter by ChIP and agarose gel.",
    "ncbi_link": "TGIF1: 7050
Twist1: 7291"
  },
  {
    "caption": "Pancreatic chromatin from control or Tgif1KO mice was analyzed for binding of TGIF1 to the Twist1 promoter by ChIP and agarose gel.",
    "ncbi_link": "Tgif1: 21815
Twist1: 22160"
  },
  {
    "caption": "PL45 stably expressing both Dox-inducible TGIF1 and Tam-inducible Twist1 (Twist1ER) were treated with Tam and/or Dox for 48 hr and analyzed for Twist1 expression by immunoblotting or qRT-PCR (n=6).",
    "ncbi_link": "TGIF1: 7050
Twist1: 7291"
  },
  {
    "caption": "MIAPaCa-2 cells were transfected with wild-type or mutated (Twist1 binding site) Twist1 luciferase reporters (TGTLuc) together with increasing amounts of Twist1 expression vector in the presence of empty vector (EV) or TGIF1 expression vector. Luciferase activity was measured 48 hr following transfection and normalized on the basis of co-transfected Renilla luciferase (n=6).",
    "ncbi_link": "Luc: 
luciferase: 
TGIF1: 7050
Twist1: 7291"
  },
  {
    "caption": "Expression of Cdh1, Vimentin, and p16Ink4A in pancreas from control, KC or KTC mice (same as in C) was analyzed by qRT-PCR (n=6).",
    "ncbi_link": "Cdh1: 12550
p16Ink4A: 12578
Vimentin: 22352"
  },
  {
    "caption": "Expression of Cdh1, Vimentin and p16Ink4A in pancreas from control, KTC or KTWC mice was analyzed by qRT-PCR (n=6).",
    "ncbi_link": "Cdh1: 12550
p16Ink4A: 12578
Vimentin: 22352"
  },
  {
    "caption": "Specificity of anti-phospho-TGIF1 (pTGIF1) antibody. Cell extracts from Tgif1-/- MEFs cells reconstituted with empty vector (EV), wild-type (TGIF1) or non-phosphorylated form (TGIF1.2TA) of Flag-TGIF1 were immunoblotted with anti-phospho-TGIF1 or β-Actin as a loading control.",
    "ncbi_link": "Tgif1: 21815
TGIF1: 21815"
  },
  {
    "caption": "MIAPaCa-2 cells were transfected with TGIF1 or TGIF1.2TD expression vectors, selected with G418 and resistance colonies were pooled (n=6). Expression of Twist1 was examined by qRT-PCR (D).",
    "ncbi_link": "TGIF1: 7050
Twist1: 7291"
  },
  {
    "caption": "MIAPaCa-2 cells were transfected with TGIF1 or TGIF1.2TD expression vectors, selected with G418 and resistance colonies were pooled (n=6). Binding of TGIF1 to the Twist1 promoter was examined by ChIP and agarose gel.",
    "ncbi_link": "TGIF1: 7050
Twist1: 7291"
  },
  {
    "caption": "BxPC3 cells were transfected with TGTLuc together with TGIF1 or TGIF1.2TA in the presence or absence of KrasG12D. Luciferase activity was measured 48 hr following transfection and normalized on the basis of co-transfected Renilla luciferase (n=6).",
    "ncbi_link": "Luc: 
luciferase: 
Kras: 3845
TGIF1: 7050"
  },
  {
    "caption": "BxPC3 cells were transfected with CDH1Luc or p16Luc reporter together with TGIF1 or TGIF1.2TA in the presence or absence of KrasG12D and luciferase activity was measured 48 hr following transfection as described in (E) (n=6).",
    "ncbi_link": "Luc: 
CDH1: 999
p16: 1029
Kras: 3845
TGIF1: 7050"
  },
  {
    "caption": "MIAPaCa-2, Suit-2, Capan-2 and Panc-1 cells were transfected with empty vector (EV), wild-type (TGIF1) or phosphorylation mimic mutant (TGIF1.2TD) of TGIF1. Cell extracts were analyzed 48 hr following transfection by immunoblotting using anti-Flag antibody (C).",
    "ncbi_link": "TGIF1: 7050"
  },
  {
    "caption": "MIAPaCa-2, Suit-2, Capan-2 and Panc-1 cells were transfected with empty vector (EV), wild-type (TGIF1) or phosphorylation mimic mutant (TGIF1.2TD) of TGIF1. Cells were selected with neomycin for 2-3 weeks, and counted using an automatic cell counter (D) (n=6).",
    "ncbi_link": "TGIF1: 7050"
  },
  {
    "caption": "(a,b) Dual positive cells are more prevalent in epithelial organs and cells. (a) Proportion of ACE2+TMPRSS2+ cells (y axis) per dataset (dots) from 21 tissues and organs (rows).",
    "ncbi_link": "ACE2: 59272
TMPRSS2: 7113"
  },
  {
    "caption": "(e-i) In situ validation of dual positive cells in the lung, airways, and submucosal gland. (e-g) PLISH and immunostaining in human adult lung alveoli for (e) ACE2 (white), TMPRSS2 (green) and CTSL (red), (f) ACE2 (white), TMPRSS2 (green) and HTII-280 (red), (g) ACE2 (red) and Pro-SFTPC (green). (h) PLISH and immunostaining in human large airway submucosal glands. ACE2 (red), ACTA2 (green) and DAPI (blue). (i) PLISH in human adult large airway. ACE2 (green) and DAPI (blue).",
    "ncbi_link": "HTII-280: 
Pro-SFTPC: 
ACE2: 59272
CTSL: 1514
TMPRSS2: 7113"
  },
  {
    "caption": "(a,c) Single-cell ATAC-seq of lung samples from primary carina (1C) and subpleural parenchyme (RPL) (n=1 patient, k=3 samples, 3,366 cells from 1C, 8,340 cells from RPL). Uniform Manifold Approximation and Projection (UMAP) embedding of scATAC-seq profiles (dots) colored by (a, left) cell types, (a, right) cells with at least 1 fragment (indicating accessibility, open chromatin) mapping to the ACE2 gene locus (defined as −2kb upstream the Transcription Start Site to Transcription End Site), or by sample location",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(g) Low expression in pediatric samples. Mean expression level (log CPM, y axis) of ACE2 (blue), TMPRSS2 (orange), and CTSL (green) across age bins (x axis) in AT2 (left) and ciliated (right) cells. Pediatric samples: 0-10 years. Samples from past or current smokers were removed from this plot to avoid smoking confounders. Error bars are omitted due to y-axis limitations. They are typically 10-fold the mean value (Supplementary Table 5). Multiciliated and AT2 cells are shown as these cell types are present in fetal data, and show significant age associations with ACE2 expression.",
    "ncbi_link": "ACE2: 59272
CTSL: 1514
TMPRSS2: 7113"
  },
  {
    "caption": "(a) Gradual increase in Ace2 expression by airway epithelial cell type with age. Mean expression (y axis) of Ace2 in different airway epithelial cells (x axis) of mice of three consecutive ages (color legend, upper right). Shown are replicate mice (dots), mean (bar), and error bars (standard error of the mean (SEM)).",
    "ncbi_link": "Ace2: 70008"
  },
  {
    "caption": "(b) Increase in proportion of Ace2+Ctsl+ goblet and club cells with age. Percent of Ace2+Ctsl+ cells (x axis) in different airway epithelial cell types (y axis) of mice of three consecutive ages (color legend, upper right). Shown are replicate mice (dots), mean (bar), and error bars (SEM).",
    "ncbi_link": "Ace2: 70008
Ctsl: 13039"
  },
  {
    "caption": "(c-j) Increase in Ace2 expression in secretory cells with smoking. Mice were daily exposed to cigarette smoke or filtered air as control for two months after which cells from whole lung suspensions were analyzed by scRNA-seq (Drop-Seq). (c,d) UMAP of scRNA-seq profiles (dots) colored by experimental group (c) or by Ace2+ cells and indicated double positive cells (d). Alveolar epithelial cells (AT1 and AT2) and airway epithelial secretory and ciliated cells are marked.",
    "ncbi_link": "Ace2: 70008"
  },
  {
    "caption": "(c-j) Increase in Ace2 expression in secretory cells with smoking. Mice were daily exposed to cigarette smoke or filtered air as control for two months after which cells from whole lung suspensions were analyzed by scRNA-seq (Drop-Seq). (e) The relative frequency of Ace2+ cells is increased by smoking in airway secretory cells but not AT2 cells. Relative proportion (y axis) of Ace2+ (red) and Ace2- (grey) cells in smoking and control mice of different cell types (x axis).",
    "ncbi_link": "Ace2: 70008"
  },
  {
    "caption": "(f, g) Expression of Ace2 is increased in airway secretory cells, but not in AT2 cells. Distribution of Ace2 expression (y axis) in secretory (f) and AT2 (g) cells from control and smoking mice (x axis).",
    "ncbi_link": "Ace2: 70008"
  },
  {
    "caption": "(h-j) Re-analysis of published bulk mRNA-Seq101 of lungs exposed to different daily doses of cigarette smoke show increased expression of (h) Ace2, (i) Tmprss2, and (j) Ctsl after five months of chronic exposure.",
    "ncbi_link": "Ace2: 59272
Ctsl: 1514
Tmprss2: 7113"
  },
  {
    "caption": "(k) Expression in placenta. UMAP plots showing expression of Ace2, Tmprss2 and Ctsl in single and double positive cells from embryonic days 9.5 to 18 (left) and embryonic day 14.5 (right) of mouse placenta development",
    "ncbi_link": "Ace2: 70008
Ctsl: 13039
Tmprss2: 50528"
  },
  {
    "caption": "(a) Multiple proteases are co-expressed with ACE2 in human lung scRNA-seq. Scatter plot of significance (y axis, -log10(adjusted P value)) and effect size (x axis) of co-expression of each protease gene (dot) with ACE within each indicated epithelial cell type (color). Dashed line: significance threshold. TMPRSS2 and PCSKs that significantly co-expressed with ACE2 are marked.",
    "ncbi_link": "PCSKs: 
ACE2: 59272
TMPRSS2: 7113"
  },
  {
    "caption": "A HeLa  cells were transfected with control (Ctr) or three different GCN2-targeting siRNA-s and progression  from prophase  to anaphase  was observed by  live-cell imaging. Averages (lines) and SEM (bands) from five (siCtr) or four (each siGCN2) independent experiments are shown; n= 379 for siCtr, 241 for siGCN2 #1, 170 for siGCN2 #2, 239 for siGCN2 #3. ****p<0.0001 for each of the siRNA-s (Kolmogorov-Smirnov test). t=0 denotes entry into prophase  as judged by the first frame showing chromatin  condensation.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "E, Chromosome  congression is affected by the absence of GCN2. E Immunofluorescence  images of HeLa  cells stained  for a kinetochore  marker, CREST  (grey) and DAPI  for DNA (blue). Arrowheads indicate misaligned chromosomes. Scale bars represent 5 µm.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "G­­ Increased number of mitotic  cells with tripolar spindles  after GCN2  knock-down. HeLa  cells were transfected with control (Ctr) or GCN2-targeting siRNA and fixed for immunofluorescence. The number of spindle poles was determined by using a pericentrin  antibody. Mean and SEM are shown from five independent experiments. n= 61, 27, 19, 24 and 28 for siCtr; n=49, 29, 22, 26 and 26 for siGCN2; p=0.0125, paired two-tailed t-test.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "A, B There is no significant difference in global translation rates in mitosis  after GCN2  knock-down. A HeLa  cells were pulse labeled with OPP  and fixed with 70% ethanol. OPP  was detected by Click-IT (AF 647) and mitotic  cells were identified by staining  for phospho-histone H3. 2D  flow cytometry plots are shown, where AF647  intensity corresponds to OPP  incorporation. Translation levels normalized to siCtr G1. The graph shows averages and SEM from three independent experiments. Paired two-tailed t-tests.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "A Verification of the mutants. HeLa  cells transduced with the indicated GCN2-siR constructs were transfected with control (Ctr) or GCN2-targeting siRNA. Halofuginone  (HFG) was added to 40 nM for 4 hours, and GCN2 autophosphorylation, ATF4  induction and eIF2α phosphorylation  were assessed by immunoblotting. γ-tubulin is shown as loading control. The line in the GCN2  blot indicates that a longer exposure of the same blot  is shown on the left than on the right.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "B GCN2 coimmunoprecipitates  with PP1α  and γ. HeLa  cells stably transfected with GFP-PP1α  or GFP-PP1γ  were transduced to express either GCN2-siR (wild-type) or GCN2-siR-AAXA. Cells were  arrested in prometaphase with Eg5i, GFP-PP1α  and GFP-PP1γ  were immunoprecipitated  using GFP-trap and the immunoprecipitates  were immunoblotted  for GCN2. The vertical line in the PP1α  and PP1γ blots  indicates that different exposures of the same blot  are shown for the inputs and the IP-s.",
    "ncbi_link": "GFP: 
GCN2: 440275
PP1α: 5499
PP1γ: 5501"
  },
  {
    "caption": "D GCN2   can phosphorylate PP1α  and γ in vitro. HeLa  cells carrying GFP-PP1α  or GFP-PP1γ  were arrested in prometaphase  with an Eg5  inhibitor (Lane 3), then GFP-tagged PP1α  or PP1γ  were immunoprecipitated  using GFP-trap (input, Lane 2). The immunoprecipitates  were incubated in kinase  buffer and ATP  with constitutively active, recombinant GCN2. The samples were run on phos-tag gels and immunoblotted  with PP1γ  or PP1α  antibody.",
    "ncbi_link": "GFP: 
PP1α: 5499
PP1γ: 5501"
  },
  {
    "caption": "F PP1α  and PP1γ  bandshifts are diminished in cells depleted for GCN2  and arrested in mitosis. HeLa  cells were transfected with control or GCN2-targeting siRNA and arrested in prometaphase  using a PLK1  inhibitor. Representative quantifications of the ratios of the phospho-PP1/PP1 signal (average and SEM) from four independent experiments are shown. *p=0.0217 (PP1α) and **p=0.0069 (PP1γ) (paired two-tailed t-tests).",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "HeLa  cells were transfected with control or GCN2-targeting siRNA and fixed for immunofluorescence. Representative image of mitotic  cells stained  for A ChTOG  (magenta), tubulin  (green) and DNA  (blue), Scale bars represent 5 µm. Percentage of cells displaying the aberrant localizations  Averages and SEM from three independent experiments are shown. For chTOG  n= 29, 37, 44 for siCtr; n= 14, 41, 28 for siGCN2; **p=0.0063 (paired two-tailed t-tests).",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "HeLa  cells were transfected with control or GCN2-targeting siRNA and fixed for immunofluorescence. Representative image of mitotic  cells stained  for B CENPE  (magenta), P-Aurora B  (yellow), tubulin  (green) and DNA (blue) are shown. Scale bars represent 5 µm. D Percentage of cells displaying the aberrant localizations  Averages and SEM from three independent experiments are shown. For CENPE  n= 15, 35, 43 for siCtr; n= 11, 21, 20 for siGCN2; **p=0.001, for P-Aurora B n=29, 37, 44 for siCtr; n= 14, 41, 28 for siGCN2; **p=0.0053 (paired two-tailed t-tests).",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "HeLa  cells were transfected with control or GCN2-targeting siRNA, synchronized in the cell cycle by thymidine  block-and-release and samples were collected for  flow cytometry  at the indicated time points. A Cell-cycle progression in the cells synchronized by thymidine  block-and-release, three independent experiments, averages and SEM are shown.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "HeLa  cells were transfected with control or GCN2-targeting siRNA, synchronized in the cell cycle by thymidine  block-and-release and samples were collected for immunoblotting  at the indicated time points. B Representative immunoblots  of TACC3-S558 phosphorylation  and  Aurora A-T288 phosphorylation",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "B HeLa  cells were transfected with control or GCN2-targeting siRNA or treated with the indicated concentrations of GCN2  inhibitor, cells were fixed after 72 h incubation, and the number of cells containing micronuclei  was determined by DAPI staining. Four independent experiments, averages with SD are shown. n= 187, 72, 162, 531 for siCtr; n= 159, 112, 200, 656 for siGCN2; p= 0.009; n=721, 821, 682 for 0 µM; n= 607, 585, 635 for 1 µM, n= 414, 510, 723 for 2 µM; n= 123, 147, 280 for 3 µM; p=0.004 for 1 µM, **p=0.005 for 2 µM, **p=0.005 for 3 µM (paired two-tailed t-tests).",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "A C57BL/6 WT or Rag2−/− mice were immunosuppressed with hydrocortisone +/− FK506 and infected with 105 AF CEA10 conidia intranasally. Mortality was assessed using a 20% weight loss endpoint. Mortality was significantly increased in FK506 immunosuppressed mice reaching 100% by day 10 p.i. (P = 0.003 for HC versus HC+FK506 in Rag2−/− using log-rank test, n = 10 per group).",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "B, C PAS-stained lung sections of Rag2−/− mice were scanned and inflammation quantified by pixel intensity threshold analysis in ImageJ. FK506-treated animals had increased inflammation at day 2 p.i. compared to control. P = 0.0126 (using Student's t-test), n = 3-5 per group. (C) Close-up of an infectious focus showing increased inflammation and fungal growth in the FK506-treated group. Scale bar: 400 μm.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "At 2 days post-fertilization (dpf),Lyz:dsRed or mpx:GFPlarvae were transferred into DMSO ctrl or FK506 (1 μg/ml) containing 0.5 × E2. At 3 dpf, zebrafishlarvae were microinjected with AFeGFPconidia into the hindbrain and mortality, and fungal burden and neutrophil recruitment were assessed.A, B Absolute neutrophil numbers in treated and untreated mpx:GFPlarvae were quantified by direct counting of fluorescent neutrophils in non-infected whole fish (n = 11-13 per group). There were no significant differences.",
    "ncbi_link": "Lyz: 677744
mpx: 337514"
  },
  {
    "caption": "At 2 days post-fertilization (dpf),Lyz:dsRed or mpx:GFPlarvae were transferred into DMSO ctrl or FK506 (1 μg/ml) containing 0.5 × E2. At 3 dpf, zebrafishlarvae were microinjected with AFeGFPconidia into the hindbrain and mortality, and fungal burden and neutrophil recruitment were assessed.C For survival analysis, lyz:dsRedlarvae were microinjected with ˜10 conidia and the effects of FK506 on the outcome from invasive aspergillosis was determined by Kaplan-Meier analysis for survival over 6 days post-infection (n = 16 per group). Immunosuppression led to a significant increase in mortality.",
    "ncbi_link": "Lyz: 677744
lyz: 677744"
  },
  {
    "caption": "At 2 days post-fertilization (dpf),Lyz:dsRed or mpx:GFPlarvae were transferred into DMSO ctrl or FK506 (1 μg/ml) containing 0.5 × E2. At 3 dpf, zebrafishlarvae were microinjected with AFeGFPconidia into the hindbrain and mortality, and fungal burden and neutrophil recruitment were assessed. D TNF-α mRNA levels were measured in whole non-infected or infected larvae 48 h p.i. Immunosuppression led to significant and almost complete inhibition of TNF-α expression during infection.",
    "ncbi_link": "Lyz: 677744
mpx: 337514
TNF-α: 114461"
  },
  {
    "caption": "At 2 days post-fertilization (dpf),Lyz:dsRed or mpx:GFP larvae were transferred into DMSO ctrl or FK506 (1 μg/ml) containing 0.5 × E2. At 3 dpf, zebrafishlarvae were microinjected with AF eGFP conidia into the hindbrain and mortality, and fungal burden and neutrophil recruitment were assessed. E-G Lyz:dsRedlarvae were infected with ˜50 eGFP-expressing conidia of A. fumigatus and were imaged daily from 24 h p.i. (E) The effects of FK506 on neutrophil recruitment were assessed by integrated density analysis of red fluorescent neutrophils at sites of infection in ImageJ. A representative image showing impaired neutrophil recruitment to the site of infection in immunosuppressed larvae is shown (60 h p.i.). The arrows indicate infectious foci. (F) Neutrophil recruitment was minimal throughout the first 60 h p.i. in immunosuppressed larvae (n = 8 per group). (G) Fungal growth was determined by measurement of the length of individual fluorescent hyphal elements (n = 8 per group).",
    "ncbi_link": "Lyz: 677744"
  },
  {
    "caption": "B J774A.1 cells were treated with FK506 (10 ng/ml) and either left non-stimulated (NS) or stimulated with AF SC (MOI=1) for 6 h. TNF-α mRNA levels were quantified from whole-cell RNA extracts by RT-PCR. FK506 significantly reduced TNF-α expression.",
    "ncbi_link": "TNF-α: 21926"
  },
  {
    "caption": "C J774A.1 macrophages were treated with control (Ctrl.) or calcineurin A (CnA)-targeting siRNA (50 nM) and stimulated with either AF SC (MOI = 1), zymosan (50 μg/ml) or LPS (25 ng/ml) overnight. TNF-α was measured in the culture supernatant by ELISA. CnA siRNA led to significant reductions in both AF- and zymosan-dependent TNF-α levels, but had no significant effect on LPS responses.",
    "ncbi_link": "calcineurin A: 19055
CnA: 19055"
  },
  {
    "caption": "A BMDMs from WT, Dectin-1−/− or MyD88−/− mice were infected with swollen conidia (MOI = 1), and TNF-α was measured in the SN after overnight incubation. TNF-α levels were significantly reduced in Dectin1−/− and Myd88−/− BMDMs.",
    "ncbi_link": "Dectin-1: 56644
Dectin1: 56644
MyD88: 17874
Myd88: 17874"
  },
  {
    "caption": "B BMDMs were stimulated with swollen conidia (MOI = 5) or zymosan (50 μg/ml), and NFATc2 translocation was quantified by confocal microscopy 30 min after stimulation. Whilst almost complete abrogation of NFAT translocation was seen in Dectin1−/−macrophages stimulated with zymosan, NFAT responses to AF were unaffected.",
    "ncbi_link": "Dectin1: 56644"
  },
  {
    "caption": "C-E J774A.1 macrophages were pre-treated with (C, D) the Syk inhibitor piceatannol or (E) a control or Syk-targeting siRNA (10 nM) before stimulation with swollen conidia (MOI = 1) or zymosan (50 μg/ml). (E) Whole-cell lysates of Syk or Ctrl. siRNA-treated cells were separated by SDS-PAGE, followed by Western blotting, and membranes were probed with anti-Syk and anti-β-actin antibodies.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "C BMDMs from WT or TLR9−/−mice were infected with swollen conidia (MOI = 1), and after overnight stimulation, TNF-α was measured in the SN by ELISA. TLR9−/− BMDMs had significantly lower TNF-α levels.",
    "ncbi_link": "TLR9: 81897"
  },
  {
    "caption": "D, E BMDMs from WT or TLR9−/−mice were infected with swollen conidia (MOI = 5) for 30 min, and NFATc2 translocation was quantified by (D) confocal microscopy. TLR9−/− BMDMs exhibited reduced NFATc2 translocation by both approaches.",
    "ncbi_link": "TLR9: 81897"
  },
  {
    "caption": "G BMDMs from WT or MyD88−/−mice were pre-treated with ODN2088 (10 μM) and infected with swollen conidia (MOI = 5) for 30 min. NFATc2 translocation was quantified by confocal microscopy. In both, WT and MyD88−/− BMDMs, blocking TLR9 significantly impaired NFATc2 translocation.",
    "ncbi_link": "MyD88: 17874"
  },
  {
    "caption": "C J774A.1 macrophages were treated with a control or BTK-targeting siRNA (25 nM), and NFAT translocation was quantified by confocal microscopy. BTK knock-down led to a significant reduction in NFATc2 translocation in response to AF.",
    "ncbi_link": "BTK: 12229"
  },
  {
    "caption": "D, E J774A.1 macrophages were treated with a control, BTK (25 nM)- or TLR9 (75 nM)-targeting siRNA and additionally pre-treated with either ODN2088 (10 μM) or the BTK inhibitor LFM-A13 (12.5 μM). The cells were infected with swollen conidia (MOI = 5), and NFATc2 translocation was measured by confocal microscopy. Blocking both TLR9 and BTK signalling had no additive effect on NFAT translocation blockade.",
    "ncbi_link": "BTK: 12229
TLR9: 81897"
  },
  {
    "caption": "Tap-1 is required for the secretion of TseL. Pellet (P) and supernatant (S) of bacterial cultures were analyzed by SDS-PAGE. The result of immunoblotting with antisera against TseL and Hcp and purified antibodies against DnaK is shown. The asterisk marks an unspecific band, detected by the antiserum against TseL, present in the pre-immunized serum. One representative experiment of three independent experiments is shown.",
    "ncbi_link": "Tap-1: "
  },
  {
    "caption": "Tap-1 is required for TseL-mediated killing. Wild-type C6706 or C6706 lacking tsiV1 were exposed to the indicated V52 mutants in a killing assay. The y-axis indicates the number of surviving C6706.",
    "ncbi_link": "Tap-1: 
TseL: 
tsiV1: "
  },
  {
    "caption": "Tap-1 is required for TseL function. Killing assays in which V52Δtap-1 was mixed with wild-type C6706 or mutants lacking tsiV1, tsiV2, or tsiV3. The y-axis indicates surviving C6706.",
    "ncbi_link": "tap-1: 
Tap-1: 
tsiV1: 
tsiV2: 
tsiV3: "
  },
  {
    "caption": "TseL secretion depends on VgrG-1. Western blot analysis of pellet (P) and supernatant (S) samples of the indicated strains. Samples were immunoblotted with antisera against TseL and Hcp and purified antibodies against DnaK. The unspecific band detected by rabbit serum is marked with an asterisk. One representative of three experiments is shown.",
    "ncbi_link": "VgrG-1: "
  },
  {
    "caption": "VgrG-1 is required for TseL-mediated killing. Killing assay with wild-type V52 or indicated mutants and wild-type C6706 or a mutant lacking the immunity gene tsiV1. The y-axis indicates surviving C6706.",
    "ncbi_link": "TseL: 
tsiV1: 
VgrG-1: "
  },
  {
    "caption": "VasX- and VgrG-3-mediated killing but not TseL-mediated killing occurs in the absence of VgrG-1. V52ΔvgrG-1 was mixed in a killing assay with wild-type C6706 or mutants lacking immunity genes tsiV1, tsiV2, or tsiV3 (specific for TseL, VasX, and VgrG-3, respectively). The y-axis indicates surviving C6706.",
    "ncbi_link": "TseL: 
tsiV1: 
tsiV2: 
tsiV3: 
VasX: 
vgrG-1: 
VgrG-1: 
VgrG-3: "
  },
  {
    "caption": "A, B Interactions between Tap-1 and TseL (A) or VgrG-1 (B). Shown are immunoblots of lysates (total) and immunoprecipitates with anti-FLAG affinity beads (IP:FLAG) of V52Δtap-1 (A) or V52 vgrG-1::myc (B) transformed with empty vector or a plasmid encoding His-tagged or FLAG-tagged Tap-1.",
    "ncbi_link": "tap-1: 
Tap-1: 
vgrG-1: "
  },
  {
    "caption": "C Interaction between TseL and VgrG-1. Shown are immunoblots of lysates (total) and immunoprecipitates with an anti-FLAG affinity beads (IP:FLAG) of V52 or V52Δtap-1 transformed with empty vector or a plasmid encoding HIS-tagged or FLAG-tagged VgrG-1.",
    "ncbi_link": "tap-1: 
VgrG-1: "
  },
  {
    "caption": "Specificity of the C-terminal Tap-1 segment. Killing assay in which the lack of tap-1 in V52 is complemented by empty vector (control) or one of two different alleles of tap-1. The ability to kill in a TseL-dependent manner is indicated by the logarithm of surviving C6706ΔtsiV1.",
    "ncbi_link": "Tap-1: 
tap-1: 
tsiV1: "
  },
  {
    "caption": "Specificity of N-terminal segment of Tap-1. Killing assay in which the lack of tap-1 in 1587 is complemented by empty vector (control) or one of two different alleles of tap-1. The ability to facilitate killing by the effector A55_1502 is indicated by the logarithm of surviving 1587ΔA55_1501-03.",
    "ncbi_link": "A55_1502: 
Tap-1: 
tap-1: "
  },
  {
    "caption": "(A) Western blot of SMC3-LAP expressing HeLa cells treated with siRNA as indicated and synchronized in G2-phase. Efficiency of RNA interference and SMC3 acetylation levels were analyzed from total extracts and after chromatin fractionation (asterisks indicate unspecific signals that were depleted from antibody dilutions used in later experiments, presumably by repeated usage of the antibody samples). Note that ESCO1 levels were increased on chromatin after depletion of ESCO2, raising the possibility that a decrease in chromatin bound ESCO2 might be compensated for by ESCO1 recruitment to chromatin.",
    "ncbi_link": "ESCO1: 114799
ESCO2: 157570"
  },
  {
    "caption": "(A) Quantification of iFRAP experiments using HeLa cells expressing SMC3-LAP in the wild-type form (wt) or with lysines 105-106 mutated to glutamines (QQ) or arginines (RR) and synchronized in G1-phase. Error bars denote s.e.m., n > 25 cells per condition.(B) Quantification of chromatin residence time of SMC3-LAP alleles in G1-phase.",
    "ncbi_link": "SMC3: 13006"
  },
  {
    "caption": "(E) Western blot of mouse fibroblasts expressing SMC3-LAP in the presence or absence of endogenous Smc3 after gene deletion. Extracts were prepared after subculturing two times. Cells without SMC3-LAP do not proliferate after deletion of Smc3.",
    "ncbi_link": "Smc3: 13006"
  },
  {
    "caption": "(F) Western blot showing HeLa cell extracts after treatment with siRNA as indicated and synchronized in G2-phase. Note that ESCO1 immunoblot signals were also reduced in sororin depleted cells. We currently do not know if this is an effect of sororin depletion, an off-target effect or an artefact of unequal sample loading.",
    "ncbi_link": "sororin: 113130
ESCO1: 114799"
  },
  {
    "caption": "(A) FACS profile of cells transfected with nondegradable KEN-box mutant sororin-FLAG (sorKBM-FLAG) after synchronization in G1-phase and propidium iodide staining.",
    "ncbi_link": "sororin: 113130"
  },
  {
    "caption": "(A) Schematic representation of wild-type (wt), targeted (flx) and deleted (Δ) Cdca5 alleles (left) and Southern blot of mouse genomic DNA (right). Red triangles, loxP sites.",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(B) Observed and expected genotype distribution among offspring of heterozygous Cdca5 Δ/+ mice (newborn mice, n = 136; E9.5, n = 54).",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(D) Western blot of cell extracts to analyze depletion of sororin protein from fibroblasts after tamoxifen-induced Cre expression. Extracts were prepared either one or two days after release from the arrest as indicated. Chr, fractionated chromatin; sol, soluble proteins.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "(G) Quantification of mitotic cells with misaligned chromosomes after Cdca5 deletion and proliferation for 36 to 60 hours. Size bar, 10 µm; error bars denote s.e.m.; n > 500 cells per condition.",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(H) Phenotypic classification of nuclear morphology after Cdca5 deletion and proliferation for 5 to 7 days. Size bar, 10 µm; error bars denote s.e.m.; n > 500 cells per condition.",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(I) Western blot showing protein depletion efficiency. Cre expression was induced with tamoxifen for 24 hours in proliferating Smc3 and Cdca5 conditional knockout immortalized fibroblasts.",
    "ncbi_link": "Cre: 
Cdca5: 67849"
  },
  {
    "caption": "(J) Analysis of chromosome spreads after Smc3 or Cdca5 deletion and nocodazole treatment. Representative images from every category are shown; size bar, 10 µm; error bars denote s.e.m.; n > 500 per genotype.",
    "ncbi_link": "Cdca5: 67849
Smc3: 13006"
  },
  {
    "caption": "(A) Schematic illustration of the LAP-AID-tag integrated into the bacterial artificial chromosome containing the mouse Cdca5 locus.(B) Immunofluorescence staining of cells expressing sor-LAP-AID and the F-box helper protein after treatment with auxin. Antibodies against GFP mark the fusion protein and Aurora B antibody stains cells in G2/M-phase. Scale bar, 10 µm.(C) Quantification of immunofluorescence after treating cells with auxin. Error bars denote s.e.m.; a.u., arbitrary units.(D) Time course quantification of GFP immunofluorescence signal decrease after auxin addition.",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(A) Cell cycle distribution of immortalized Cdca5 Δ/Δ sor-LAP-AID fibroblasts after 24-hour incubation with aphidicolin and release.",
    "ncbi_link": "Cdca5: 67849"
  },
  {
    "caption": "(A) Z-Projection of confocal image stacks spanning 5 μm of a control embryo (left) co-expressing endogenously tagged mVenus::βH-spectrin (green) and the plasma membrane marker GAP43::mCherry (magenta) and of an embryo additionally expressing a maternally driven anti-GFP nanobody KD module to knock-down βH-spectrin (right). Co-expression of the anti-GFP nanobody KD system resulted in a drastic decrease of βH-spectrin protein levels as assessed by the fluorescent signal intensity which dropped below the detection limit.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(B) Pie diagrams quantifying the percentage of control embryos (top, n=50) and βH-spectrin knock-down embryos (bottom, n=40) that formed ventral furrow either normally or with minor phenotypes (green) and the percentage of embryos that displayed severe abnormalities or did not at all undergo tissue invagination (red). The assessment of phenotypes was done in an unbiased randomized approach.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(C-J) Confocal images of a control embryo (C,D) and βH-spectrin knock-down embryos with a minor phenotype (E,F), with a severe phenotype that underwent tissue invagination (G, H) and with a severe phenotype that did not undergo tissue invagination (I, J). Surface view is shown in (C,E,G,I) and the cross section through the tissue at two different time points in (D,F,H,J). All embryos expressed the plasma membrane marker GAP43::mCherry. Scale bars, 20 μm.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(K, L) Quantification of apical surface area (K) and anisotropy (L) in control embryos (green, nControl: 6 embryos) and in βH-spectrin knock-down embryos (red, nβH-spectrin KD: 7 embryos). Solid lines indicate the mean values and the semi-transparent regions the corresponding standard deviation.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(D, E) Still frames of a movie showing endogenously tagged mVenus::βH-spectrin in the cross section of a gastrulating wild type (D) and twist mutant (E) embryo imaged using two-photon microscopy. The top frame corresponds to the time point where an initial bending of the apical surface was observed, the middle frame was taken 2 min and the lower frame 3 min afterwards. Scale bars, 30 µm.",
    "ncbi_link": "twist: 37655"
  },
  {
    "caption": "(F, G) Confocal images showing apical βH-spectrin (endogenously tagged mVenus::βH-spectrin) in a wild type (F) and twist mutant (G) embryo. Scale bars, 20 μm. Medio-apical βH-spectrin fibers observed in wild type embryos were absent in twist mutant embryos.",
    "ncbi_link": "twist: 37655"
  },
  {
    "caption": "(A-C) Confocal images of the apical cell surface of a βH-spectrin knock-down embryo showing the myosin-II marker Sqh::mCherry (green) and E-cadherin::mNeonGreen (magenta) during ventral furrow formation. (A) myosin-II accumulates normally at the apical surface and cells undergo an initial phase of constriction. The dashed rectangle indicates the region shown in (B and C) at higher magnification. Scale bar, 30 μm. Panels (B,C) show a sub-region within the ventral tissue at different time points. Initially a supracellular myosin-II network formed (0 s), before intercellular connections broke (13 s) resulting in membrane tears (dashed line) with tissue retractions (small arrow heads) along the anterior-posterior axis. The intercellular network re-established (39 s, 65 s) as new actomyosin fibers formed (big arrow heads) to reconnect neighboring cells. The intercellular network broke again causing tears (dashed lines) at different positions (104 s). Scale bars, 5 μm.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(D,E) Confocal images showing the myosin-II marker Sqh::mCherry (green), E-cadherin::mNeonGreen (magenta) and the segmented membrane (red) of a single cell at different time points in a control embryo undergoing ratcheted constriction (D) and in a βH-spectrin knock-down embryo undergoing non-ratcheted pulsations (E). Scale bars, 2.5 μm.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(F) Heatmaps showing the apical surface of individual cells over time of control embryos (left) and βH-spectrin knock-down embryos (right) normalized to the initial time point (nControl=233; nβH-spectrinKD=368; of 5 different embryos each). The color-coded scale bar is depicted on the left. Dark blue indicates a cell area bigger than the initial value (>1) and yellow indicates an area constricted to less than 1/5 of the initial area (<0.2). Three different cell behaviors in βH-spectrin knock-down embryos were identified: cells that constricted, cells that showed impaired constriction and cells that expanded.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(G) Quantification of the percentage of cells that constricted (to an area < 50%, yellow), cells that showed impaired constriction (to an area >50 and <100%, green) and cells that expanded (to an area >100%, blue) after 7 min in control embryos and in βH-spectrin knock-down embryos.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(H,I) Graph showing the average area over time of control cells (H, n=235 cells) and cells in βH-spectrin knock-down embryos (I) that constricted (yelow, n=274), of cells that showed impaired constriction (green, n=232) and of cells that expanded (blue, n=32). The lines indicate the mean value and the semi-transparent region the standard deviation.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(J) Boxplots showing the distribution of apical cell area values 7.5 min after the onset of ventral furrow formation of ventral cells in control embryos, of ventral cells in βH-spectrin knock-down embryos that constricted, and ventral cells in βH-spectrin knock-down embryos that displayed impaired constriction and expanded. Sample numbers are equal to I. The values are presented as percentage of initial cell area. ANOVA result (all data points): F(3,717)=763.9, p=9.6e-223; Cohen's d compared to the control: dconstricted=0.1, dimpaired=1.5, dexpanded=3.7. Due to a big effect size (high sample number), statistical significance was assessed based on Cohen's d. A Cohen's d < 0.5 was considered not significant (n. s.).",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "(K) Quantification of the peak constriction rate and expansion rate relative to control cells. Control cells and cells in βH-spectrin knock-down embryos that showed impaired constriction or expanded were compared. The mean value and standard deviation are shown. Please note the logarithmic scale. While in βH-spectrin knock-down cells the constriction rate was ~24% lower (mean value of 0.8) compared to control cells, the expansion rate increased to ~60% (mean value of 1.6). The absolute change of the expansion rate was 2.5 times higher than the change of the constriction rate. ANOVA result (all data points): F(3,717)=349.2, p=9.7e-140; pairwise comparison of βH-spectrin knock-down cells to control using Cohen's d>1.4.",
    "ncbi_link": "βH-spectrin: 38418"
  },
  {
    "caption": "A HeLa-H2B/tub cells were transfected with control or TIAR siRNAs for 48 hours and synchronized by double thymidine (TT) block. After release from the block, mitotic cells were counted by fluorescence microscopy (mean ± SD; n = 3). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "Western blot analysis of unsynchronized HeLa-H2B/tub cells was carried out to monitor expression of p(S10)-H3, total H3 and TIAR in control and TIAR-depleted cells (mean ± SD; n = 3). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "D HeLa cells were transfected with control or TIAR si-RNAs, alone or together with Cdc25B siRNA. 72 hours after transfection, p(S10)-H3-positive cells were quantified by flow cytometry (mean ± SD; n = 3). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "Cdc25B: 994
TIAR: 7073"
  },
  {
    "caption": "HeLadox-YFP-TIARr cells were transfected with control or TIAR siRNAs, and 24h hours later cell were cultured in the abscence or presence of 1 μg/ml doxocycline for 48 hours. The expression of p(S10)-H3, total H3 and TIAR was measured by Westen blot analysis. The graph shows the quantification of p-H3 levels normalized to total H3 (mean ± SD, n = 4). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "F HeLadox-YFP-TIARr-RRM123m cells were analyzed as in panel (E) (mean ± SD, n = 4). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "G HeLadox-YFP-TIARr-dQRD cells were analyzed as in panel (E) (mean ± SD, n = 4). Data information: Statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "A Following transfection of HeLa cells with control or TIAR siRNAs for 72 hours, mitotic cells were analyzed by IF microscopy and scored for chromatin (mean ± SE, n = 3). B HeLa cells were analyzed as in (A) and scored for spindle defects (mean ± SE, n = 3). Data information: statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "C HeLa cells were transfected with control or TIAR siRNAs for 4 days, and subjected to colcemid for 2 hours prior to preparation of metaphase spreads. Chromosomes were stained with Hoechst (red) and anti-CENP-A antibody (green); the yellow arrowhead marks a chromosome break.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "F HeLa cells were transfected with control or TIAR si-RNAs, alone or together with Cdc25B siRNA, and 4 days later subjected to colcemid for 2 hours prior to preparation of metaphase spreads. The frequency of cells with scattered chromatids was quantified (mean ± SD, n = 3 independent experiments, approximately 30 metaphase spreads were assessed per experiment and condition). G Metaphase spreads were prepared as in (F), and the frequency of cells with chromosomal breaks was quantified (mean ± SD, n = 3). Data information , statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001.",
    "ncbi_link": "Cdc25B: 994
TIAR: 7073"
  },
  {
    "caption": "A HeLa cells were transfected with control or TIAR siRNAs for 48 hours prior to treatment with 0.4 µM APH. Cells were fixed at regular time intervals, and p(S10)-H3-positive cells were quantified by flow cytometry (mean ± SE, n = 3).",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "B HeLa cells transfected with control or TIAR siRNAs were treated with APH for 24 hours. Pan-nuclear γH2AX signals were quantified by HTM (n = 3, 2000 cells examined per experiment and condition). Each dot represents the signal from one cell, horizontal lines indicate mean values, and the blue area delineates cells above an arbitrarily chosen threshold. Data information: statistical significance was determined by Wilcoxon rank-sum test. ; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "C Chromatin-bound RPA2 signals were quantified by HTM HeLa cells transfected with control or TIAR siRNAs (n = 3, 600 cells examined per experiment and condition).",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "D HeLa cells were transfected with control or TIAR siRNAs for 72 hours prior to treatment with ATRi (5 μM.) alone or together with Ro3306 (5 μM) for 12 hours. Pan-nuclear γH2AX signals were quantified by HTM (n = 3, 1000 cells examined per experiment and condition). Data information: statistical significance was determined by Wilcoxon rank-sum test. ; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.",
    "ncbi_link": "ATR: 545
TIAR: 7073"
  },
  {
    "caption": "E HeLa cells were transfected with control or TIAR siRNAs were treated with ATRi for 48 hours, and the sub-G1 population was quantified by flow cytometry following propidium iodide staining (mean ± SD, n = 3). Data information: statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.",
    "ncbi_link": "ATR: 545
TIAR: 7073"
  },
  {
    "caption": "F HeLa cells transfected with control or TIAR siRNAs were treated with APH, alone or in combination with Gö6976 (1µg/ml) or UCN-01 (300 nM). After 24 hours, p(S10)-H3-positive cells were quantified by flow cytometry, and expressed relative to the values in the untreated condition (mean ± SE, n = 3). Data information: statistical significance was determined by unpaired Student's t-test; *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "C HeLa cells transfected with control or TIAR siRNAs were treated with 0.4 µM APH 24 hours prior to fixation. Cells were processed for IF microscopy after staining with anti-PRP19 and anti-CDK1 antibodies. Intensity profiles from staining of the same cells with anti-TIAR and anti-CDK1 antibodies are depicted on the right side.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "D CDK1 was immunoprecipitated from HeLa cells transfected with control or TIAR siRNAs, tested for in vitro kinase activity using recombinant histone H1 as substrate, and visualized by Western blot analysis and autoradiography. The mean CDK1 activity ± SE was quantified from n = 5 experiments. Data information statistical significance was determined by unpaired Student's t-test. ; *, p < 0.05; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "F HeLa cells were transfected with control or TIAR siRNAs for 72 hours before measuring expression levels of p(S22)-Lamin A by Western blot analysis (mean ± SE, n = 3). Data information statistical significance was determined by unpaired Student's t-test. ; *, p < 0.05; ***, p < 0.001.",
    "ncbi_link": "TIAR: 7073"
  },
  {
    "caption": "A) Representative images of Caco-2 cysts transfected with control siRNA (siGlo) or siRNAs targeting ROCK1 and ROCK2, fixed and stained for prominin-1, F-actin (Phalloidin) and Nuclei (Hoechst). Confocal Z-sections of cysts are displayed. Arrowheads show non-protruding cells. Arrows point to protruding cells. White stars mark nuclei that are off-centered relative to the cyst's monolayer. Scale bars: 20 μm.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "B) Representative confocal images of Caco-2 cysts treated with ROCK inhibitors Y27632 and H1152, non-treated (NT) or transduced with ROCK1 and ROCK2 shRNAs (shROCK1+2). The cysts were fixed 2 days after invasion and stained for E-cadherin, F-actin (Phalloidin) and nuclei (DAPI). Boxed regions i and ii are displayed at high magnification. White arrowheads point to non-protruding cells, green arrowheads point to the apical pole, arrows point to protruding cells and white stars show off-centered nuclei. Scale bar: 20 μm.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "C) Bar graph representing the percentage of protrusive Caco-2 cysts from three independent experiments. Caco-2 cysts non-treated (NT), incubated with ROCK inhibitors Y27632 and H1152 or infected with lentiviruses encoding shRNA control and targeting ROCK1 and ROCK2. The cysts were fixed 2 days after invasion, over 100 cysts were counted for each condition. Error bar represents the Standard Error of the Mean (Means ± SEM). P values were calculated using unpaired t-test (***p<0.001, **p<0.01).",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "E) The number of cells that have invaded from the top to the bottom chamber of the Boyden chamber was quantified by automated segmentation in non-treated (NT), in ROCK inhibited conditions (Y27632, H1152) or in cells transfected with siRNA against ROCK1 and ROCK2 (siROCK1+2). The number of cells that have invaded was normalized to control conditions and reported as the average invasion rate from at least three independent experiments (Means ± SEM). P values were calculated using unpaired t-test (****p<0.0001, **p<0.01).",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "A) Caco-2 cysts expressing an empty vector (pLKO) or shROCK1 (#02) or shROCK2 (#36) after 2 days of invasion were fixed and stained for E-cadherin, F-actin (Phalloidin) and nuclei (DAPI). Boxed regions i, ii and iii are shown at high magnifications. Arrowheads point to non-protruding cells. Arrow points to protruding cells. White stars show nuclei that engage in protrusions. Scale bars: 20μm. B) The number of protrusive Caco-2 cyst was quantified in each of the mentioned conditions and represented in a bar graph as percentage of total cysts (Means ± SEM of at least 3 independent experiments, paired t-test, ***p<0.001, *p<0.05 n.s: non significant). ",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "C) Caco-2 cysts stably expressing GFP alone or GFP-ROCK2DN#2, were submitted to a 2 days period invasion assay, then fixed and stained for F-actin (Phalloidin) and nuclei (DAPI). Boxed regions i, ii and iii are shown at high magnification. Arrowheads point to non-protruding cells. Arrows point to protruding cells. White and black stars show nuclei that engage in protrusions. Scale bars: 20μm. D) Bargraph representing the percentage of protrusive cysts transduced with GFP (CTRL, with or without Y27632) or with ROCK2DN#2 (Means ± SEM of at least 3 independent experiments, paired t-test, **p<0.01 n.s: non significant). ",
    "ncbi_link": "GFP: 
ROCK2: 9475"
  },
  {
    "caption": "E) T84 cells grown in 3D organotypic culture form polarized cysts with a central lumen that display protruding leader cells at the basal pole (arrows) reminiscent of collective invasion. T84 cysts were transduced with lentiviruses encoding inducible GFP or Venus-ROCK2-DA and treated with doxycycline 1μg/ml. Scale bars: 20μm.",
    "ncbi_link": "GFP: 
Venus: 
ROCK2: 9475"
  },
  {
    "caption": "F) Bar graph representing the percentage of protrusive T84 cysts in control (WT), treated with ROCK inhibitor (Y27632) or transduced with lentiviruses expressing GFP or GFP-ROCK2-DA after induction by Doxycycline (Means ± SEM of at least 3 independent experiments) (paired t-test, ***p<0.001, *p<0.05).",
    "ncbi_link": "GFP: 
ROCK2: 9475"
  },
  {
    "caption": "G) Overall Survival Prognostic value of ROCK2 expression in colon cancer patients of the GSE33582 data set (n=477 patients with survival annotation) using Kaplan-Meier survival analysis. The patient cohort was divided into tumours with or without a down-regulation of ROCK2 relatively to non-tumoural tissues (expression cut-off value corresponds to the 1st decile of ROCK2 expression in non-tumoural sample, i.e. 7.6). Log-rank test p-values for survival distribution difference are indicated at 3 and 5 years.",
    "ncbi_link": "ROCK2: 9475"
  },
  {
    "caption": "B) DIC acquisition of fixed mosaic Caco-2 cysts expressing GFP alone, GFP-ROCK2DN#1 or GFP-ROCK2DN#2. Boxed regions i and ii are shown at high magnification. Arrowheads point to non-protruding cells. Arrows point to protruding cells. Scale bars: 20μm.",
    "ncbi_link": "GFP: 
ROCK2: 9475"
  },
  {
    "caption": "C) Bar graph representing the percentage of mosaic Caco-2 cysts transduced with GFP or GFP-ROCK2DN#, with or without Y27632, harbouring a protruding morphology (Means ± SEM of at least 3 independent experiments, unpaired t-test, ***p<0.001, *p<0.05).",
    "ncbi_link": "GFP: 
ROCK2: 9475"
  },
  {
    "caption": "D) Quantification of the fate of the GFP positive cells, leader or follower, in mosaic cysts transduced with GFP-alone and treated with Y27632 (GFP+Y27632) or GFP-ROCK2DN#2 from 3 independent experiments (Means ± SEM, unpaired t-test, ***p<0.001).",
    "ncbi_link": "GFP: 
ROCK2: 9475"
  },
  {
    "caption": "A) siRNA screen performed in Caco-2 cysts treated with Y27632: Caco-2 cells transfected with control siRNA or pairs of siRNA targeting RhoGEFs were seeded in the modified 3D Boyden Chamber and grown as cysts for 3 days. Then, Caco-2 cysts were treated with Y27632 and the serum gradient was induced. After 2 days, the number of cells present on the bottom chamber were quantified by automated segmentation after Hoechst staining. The bar graph represents the mean invasion rate. Each condition was duplicated. The red dashed line represent the median invasion rate, the red full line indicates the 3 fold decrease in invasion rate. Three hits were identified: #2:ARHGEF18+RNEF, #7: SGEF+ARHGEF16 and #24: FARP1+FARP2 (Mean ±SD) .",
    "ncbi_link": "RNEF: 
SGEF: 
ARHGEF16: 27237
ARHGEF18: 23370
FARP1: 10160
FARP2: 9855"
  },
  {
    "caption": "B) Caco-2 cysts stably expressing empty vector (pGIPZ) or 2 distinct shFARP1 or shFARP2 were treated with Y27632, allowed to invade for 2 days, fixed and stained for F-actin (Phalloidin). Boxed regions i, ii, iii and iv are shown at high magnification. Arrowheads point to non-protruding cells, arrows point to protruding cells. White stars show nuclei that engage in protrusions. Scale bars: 20μm. C) Bar graphs representing the percentage of protrusive cysts formed from Caco-2 cells transduced with lentiviruses encoding pGIPZ or shRNA against FARP1 and FARP2 after treatment with Y27632 from at least 3 independent experiments (Means ± SEM, paired t-test, ns: non significant, **p<0.01). ",
    "ncbi_link": "FARP1: 10160
FARP2: 9855"
  },
  {
    "caption": "D) Representative acquisition of Caco-2 cells overexpressing GFP-FARP2 grown in 2D and stained with ZO-1, in non-treated (NT) and after 2h with Y27632 or H1152. The dashed lines crossing the cell-cell junctions (i, ii and iii) are representative of the linescans measurements. Scale bars: 20μm. E) Representative fluorescence intensity of ZO-1 (red) staining and GFP-FARP2 (green) along the dashed line i, ii and iii represented corresponding to non-treated, Y27632 or H1152 treatments)",
    "ncbi_link": "GFP: 
FARP2: 9855"
  },
  {
    "caption": "F) Bar graph representing the average ratio of GFP-FARP2 over ZO-1 fluorescence intensities measured with linescans crossing cell-cell junctions. The quantification was performed on 71 cells expressing GFP-FARP2-FL from 3 independent experiments. For each cell, between 10 and 15 lines (12 pixels wide) were drawn across random region of cell-cell junctions positive for ZO-1 staining (Mean ±SEM Unpaired t-test **p<0.01, *p<0.05).",
    "ncbi_link": "GFP: 
FARP2: 9855"
  },
  {
    "caption": "A) Caco-2 cysts stably expressing GFP (treated or not with Y27632), or Cherry-FARP2-full length (FARP2-FL), FARP2-730/733 mutant (FARP2-Mut) or FARP2 del PH 730/733 (FARP2-del/Mut) were allowed to invade for 2 days, fixed and stained for F-actin. Boxed regions i, ii, iii, iv and v are shown at high magnification. Arrowheads point to non-protruding cells, arrow points to protruding cells, white star shows nucleus that engages in protrusion. Scale bars: 20μm. B) Bargraph representing the percentage of protrusive cysts expressing GFP (treated or not with Y27632) or the mentioned GFP-FARP2 constructs from 3 independent experiments (Means ± SEM, paired t-test, **p<0,01, n.s: non significant). ",
    "ncbi_link": "Cherry: 
GFP: 
FARP2: 9855"
  },
  {
    "caption": "C) Representative images of Caco-2 cysts treated with Y27632 or Blebbistatin or transfected with siRNA targeting Myosin-IIA and allowed to invade for 2 days. After fixation, the cysts were stained for F-actin (Phalloidin) and nuclei (DAPI). Representative Y27632-induced « invasive » phenotype and Blebbistatin-induced « dendritic » phenotype are displayed. Arrows point to protruding cells, white star shows nucleus that engages in protrusion and arrowheads point to \"dendritic\" protrusions. D) Bar graph representing the percentage of cysts with the \"invasive\" or \"dendritic\" phenotypes after treatment with Y27632, Blebbistatin or siMyosin-IIA or siMyosin-IIB from at least 3 independent experiments (Means ± SEM, unpaired t-test,*p<0,05, n.s: non significant). ",
    "ncbi_link": "Myosin-IIB: 
Myosin-IIA: 4620"
  },
  {
    "caption": "E) Mature Caco-2 cysts were transduced with GFP or Cherry tagged FARP2-full length (FARP2-FL), FARP2-730/733 mutant (FARP2-Mut) or FARP2 del PH/730/733 (FARP2-del/Mut), and treated (or not, NT) with Blebbistatin. 2 days after invasion,the cysts were fixed and stained for F-actin. Boxed regions i, ii, iii and iv are shown at high magnification. Arrowheads point to non-protruding cells; arrow points to protruding cells and white stars show nucleus that engage in protrusions. Scale bars: 20 μm. F) Bargraph representing the percentage of protrusive Caco2 cysts expressing the mentioned constructs , treated or not with blebbistatin, from at least 3 independent experiments (Means ± SEM , t-test,**p<0,01, n.s: non significant). ",
    "ncbi_link": "Cherry: 
GFP: 
FARP2: 9855"
  },
  {
    "caption": "Human Aβ exhibits a biphasic profile in CSF of APP transgenic miceA, B Aβ40 and Aβ42 concentrations in CSF of male APP23 mice (heterozygous; 3 (n = 14), 6 (n = 12), 8 (n = 10), 12 (n = 11), 19 (n = 9), and 25 (n = 6) months of age). CSF Aβ40 (F(1, 56) = 22.351, P < 0.001) as well as CSFAβ42 (F(1, 56) = 38.597, P < 0.001) followed a significant quadratic trend.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "C Aβ42/40 ratio in CSF of APP23 mice showed a delayed decrease with age (F(1, 56) = 53.894, P < 0.001).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "D, E Aβ40 and Aβ42 concentrations in CSF of male and female APP24 mice (homozygous; 2 (n = 13), 3-4 (n = 16), 7-8 (n = 15), 18-19 (n = 14), 24 (n = 16), and 30 (n = 18) months of age). CSF Aβ40 followed a significant quadratic trend (F(1, 86) = 6.678, P = 0.011) and CSF Aβ42 best fitted a cubic trend (F(1, 86) = 30.599, P < 0.001).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "F Aβ42/40 ratio in CSF of APP24 mice showed a delayed decrease with age (F(1, 86) = 64.936, P < 0.001).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "G, H Aβ40 and Aβ42 in the CSF of female APP51 mice (heterozygous; 3 (n = 6), 15 (n = 8), and 24 (n = 8) months of age; 22 mice in total). CSF Aβ40 (F(1, 19) = 37.349, P < 0.001) as well as CSFAβ42 (F(1, 19) = 107.670, P < 0.001) followed a significant quadratic trend.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "I Aβ42/40 ratio in CSF of APP51 mice showed a delayed decrease with age (F(1, 19) = 26.367, P < 0.001).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "HumanAβ in CSF and brain of APP transgenic miceA APP23CSFAβ40 and Aβ42 in the same animals as shown in Fig1. CSFAβ42 and Aβ40 are expressed as percentages of levels measured in the youngest age group.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "B, C Aβ40 and Aβ42 (pmol/g wet brain) in the FA-soluble brain extract from the same APP23mice showed a robust increase with age; ANOVA revealed a significant cubic trend (F(1, 56) = 221.114, P < 0.001 and F(1, 56) = 370.947, P < 0.001, respectively).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "D APP24 CSF Aβ40 and Aβ42 in the same animals shown in Fig1 as percentage of the youngest age group.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "H, I Aβ40 and Aβ42 (pmol/g wet brain) in the brain from the same APP51 mice showed a robust increase with age; ANOVA revealed a significant quadratic trend (F(1, 19) = 12.960, P = 0.002 and F(1, 19) = 19.366, P < 0.001, respectively).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Aβplaque pathology in the brains of APP23miceAβimmunostaining (CN3 antibody, dark blue) in 25-μm sagittal brain sections shows only sparse Aβ deposits primarily in the frontal cortex of 6- to 8-month-old APP23mice. At 12 months and thereafter, there is a progressive increase in plaque number and size and a progressive involvement of different brain regions. Insets highlight the plaque characteristics at the different ages. Scale bar, 100 μm.The mean number of Aβ plaques per section per hemibrain increased with age in 3- to 12-month-old mice. Only four mice were analyzed in the 3-month-old age group, as APP23mice do not develop plaques at this age (Sturchler-Pierrat et al, 1997). The 6-, 8-, and 12-month-old age groups included 12, 10, and 11 mice, respectively (these are the same mice that were used for CSF and brainAβ measurements). Note that the Aβ plaques became too numerous and often could no longer be individually distinguished in the age groups > 12 months of age. Data are represented as group means ± SEM.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Brain sAPPβ shows an age-related increase in APP23, APP24, and APP51 micesAPPβ was measured in Triton X-100 brain extracts from largely the same mice as analyzed in Figs1 and2 and is expressed as percentages of levels measured in the youngest age group.Swedish sAPPβ showed an age-dependent increase in APP23 mice following a linear trend (F(1, 83) = 52.914, P < 0.001); APP23 from two independent batches were included in this analysis (see Materials and Methods and Supplementary Fig S2 for details).Swedish sAPPβ showed an age-dependent increase in APP24mice following a linear trend (F(1, 84) = 11.264, P = 0.001).Human wild-type sAPPβ showed an age-dependent increase in APP51 following a quadratic trend (F(1, 18) = 68.980, P < 0.001).Data information: Post hoc Dunnett's test group comparisons were always conducted between the youngest group and all other groups. All data are represented as group means ± SEM; *P < 0.05; **P < 0.01; and ***P < 0.001. For absolute values, see Supplementary Fig S2.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(Left panel) A10 cells were transfected with Flag-FMRP for 3 hr then cultured for 24 hr prior to fixation and staining for β-catenin (green), Flag (FMRP, red), and nucleus (blue). (Bottom right panel) A line was drawn through a representative cell to indicate relative intensity of RGB signals. (Top right panel) An orthogonal projection was generated by a Z-stack (240 nm interval) image set using the ZEN program (Zeiss) depicting the region surrounding the nucleus in the XY, XZ, and YZ planes",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "B. (i) HEK 293T cells were transfected with Flag-FMRP as in A, and endogenous β-catenin protein complexes were immunoprecipitated with β-catenin antibody. Co-immunoprecipitated Flag-FMRP protein was detected by Western blot analysis with the Flag antibody. Non-programmed rabbit IgG was used as a control. (ii) Primary VSMCs were harvested and subjected to an endogenous coIP analysis with either β-catenin or FMRP antibody. The corresponding protein was detected in the precipitated immunocomplex by Western blot. Non-programmed rabbit IgG was used as a control",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "(Top panel) A10 cells were transfected with GBP-Lifeact and either EYFP-β-catenin, Flag-FMRP, or mCherry-β-catenin. The cells were fixed and subjected to either fluorescence microscopy or immunofluorescent staining for Flag (red), as indicated. (Bottom panel) A10 cells were transfected with GBP-Lifeact similar to above, but with both EYFP-β-catenin and Flag-FMRP, and the cells were subjected to fluorescent microscopy and immunofluorescent staining for Flag (red)",
    "ncbi_link": "EYFP: 
Flag: 
GBP: 
mCherry: 
β-catenin: 
Lifeact: 854414
FMRP: 2332"
  },
  {
    "caption": "(Top panel) A10 cells were transfected wit EYFP-β-catenin, Flag-FMRP, or mCherry-β-catenin. The cells were fixed and subjected to either fluorescence microscopy or immunofluorescent staining for Flag (red), as indicated. (Bottom panel) A10 cells were transfected with GBP-Lifeact similar to above, but with both EYFP-β-catenin and Flag-FMRP, and the cells were subjected to fluorescent microscopy and immunofluorescent staining for Flag (red) E. A10 cells were transfected as in (D) with GBP-Lamin B1",
    "ncbi_link": "EYFP: 
Flag: 
GBP: 
Lamin B1: 
mCherry: 
β-catenin: 
Lifeact: 854414
FMRP: 2332"
  },
  {
    "caption": "A. Co-sedimentation of protein/RNA complexes on a 10-50% sucrose gradient. Cell lysates generated from the cells transfected with either siRNA targeting fmr1 or its scrambled control were ultracentrifuged in sucrose gradients; peaks corresponding to the 40S and 60S subunits, 80S monosome, and polysomes were detected by UV absorbance at 254 nm, and indicated proteins in these fractions were detected by Western blot. Corresponding total cell lysate was used as input",
    "ncbi_link": "fmr1: 2332"
  },
  {
    "caption": "(i) HEK 293T cells were transfected with empty vector or Flag-FMRP, and lysates were subjected to m7GTP-agarose pull-down as in (C)",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "(ii) HEK 293T cells were transfected with empty vector or Flag-FMRP, and lysates were subjected to GTP-agarose pull-down as in (i). E. HEK 293T cells were transfected with either siRNAs targeting fmr1 or scrambled control and were subjected to m7GTP-agarose pull-downs as in (C)",
    "ncbi_link": "Flag: 
fmr1: 2332
FMRP: 2332"
  },
  {
    "caption": "Primary VSMCs (left panel), A10 (middle panel), and HEK 293T cells (right panel) were transfected with siRNAs targeting ctnnb1 (β-catenin) or scrambled RNA. After 36 hr, the cells were pulsed with 0.5 µM puromycin for 15 min and then harvested. The puromycin incorporated peptides were detected by Western blot analysis with puromycin antibody. β-catenin blots indicated efficacy of siRNA and actin was used as a loading control. The average puromycin/actin ratio (n=3) is shown in the graphs to the right of each cell type and the error bars indicate standard deviation. A one-way ANOVA and Tukey post-hoc test was performed, with p-values indicated above the error bars",
    "ncbi_link": "β-catenin: 
ctnnb1: 12387"
  },
  {
    "caption": "A10 cells were transfected with Flag-FMRP then treated with either cycloheximide or its solvent (DMSO) for 4 hr prior to fixation. β-catenin (green), Flag (FMRP, red) were visualized by immunofluorescence. Nucleus (blue) was identified by DNA staining with Hoechst 33342. Arrows indicate a loss of β-catenin signal from the perinuclear region that was seen in the control following cycloheximide treatment",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "A10 cells were transfected with Flag-FMRP as above and then pre-treated with rapamycin or solvent (DMSO) for 1 hr in serum-free media. Serum was added for 2 hr before the cells were harvested and subjected to coIP analysis using β-catenin antibody. Non-programmed rabbit IgG was used as a control. Existence of Flag-FMRP in the immunocomplex was detected by Flag antibody and β-catenin by GFP antibody",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "A10 cells were transfected with Flag-FMRP followed by rapamycin treatment similar to (D). Cells were fixed and stained for β-catenin (green), Flag (FMRP, red), and nucleus (blue). A loss of β-catenin signal from the perinuclear region that was seen in the control is indicated by the arrows.",
    "ncbi_link": "Flag: 
FMRP: 2332"
  },
  {
    "caption": "Fluorescence analyses of GFP-ATG5 or ATG16L1-GFP stably expressed in ATG5-/- or ATG16L1-/-. Cells were amino acid starved for 2 hr prior to fixation and imaging of the GFP fluorescence. Scale bar: 10 μm.",
    "ncbi_link": "ATG16L1: 77040
ATG5: 11793"
  },
  {
    "caption": "Assessment of ATG16L1 levels in the cytosolic (C) and membrane (M) fractions in lysates of the indicated cell lines using western blot analyses and antibodies against ATG16L1. ATG16L1-/- and ATG5-/- stably expressed ATG16L1-GFP while ATG3-/- stably expressed Flag-S-ATG16L1. Antibodies against α-tubulin and integrin β1 were used as controls for fractionation. Exogenous (exo) ATG16L1 was detected using antibodies against ATG16L1.",
    "ncbi_link": "ATG16L1: 77040
ATG3: 67841
ATG5: 11793"
  },
  {
    "caption": "Lack of WIPI2 expression is confirmed by western blot analyses in wild type MEFs (WIPI2+/+) and WIPI2-/- cells.",
    "ncbi_link": "WIPI2: 74781"
  },
  {
    "caption": "Immunofluorescence analyses of ATG16L1-/- and WIPI2-/- stably expressing Flag-S-ATG16L1. Cells were amino acid starved (AA starve) for 2 hr in the presence or absence of 3'MA (and additional pretreatment for 30 min) followed by fixation and immuno-staining using antibodies against Flag tag to detect ATG16L1. Scale bar: 9 μm.",
    "ncbi_link": "ATG16L1: 77040
WIPI2: 74781"
  },
  {
    "caption": "U2OS cells expressing Flag-ATG16L1∆2 or Flag-ATG16L1∆2∆182-205 were treated as in (B) and stained using antibodies against Flag tag (to detect ATG16L1, green) and FIP200 (red). Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
ATG16L1: 77040"
  },
  {
    "caption": "Protein-protein interaction assay in 293T cells transiently transfected with the indicated Flag-S-tagged ATG16L1 constructs. S tag pull down was performed and protein complexes were analysed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "Flag: 
ATG16L1: 77040"
  },
  {
    "caption": "Homodimerisation assay in 293T cells transiently transfected with ATG16L1-GFP and the indicated Flag-S-tagged ATG16L1 constructs. S tag pull down was performed and protein complexes were analysed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "Flag: 
GFP: 
ATG16L1: 77040"
  },
  {
    "caption": "Homodimerisation assay in 293T cells transiently transfected with ATG16L1-GFP and the indicated Flag-S-tagged ATG16L1 constructs. S tag pull down was performed and protein complexes were analysed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "Flag: 
GFP: 
ATG16L1: 77040"
  },
  {
    "caption": "Flag-ATG16L1WT or Flag-ATG16L1∆182-205 were stably expressed in ATG5-/- cells and analysed by immunofluorescence using antibodies against Flag tag to detect ATG16L1. Scale bar: 9 μm.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
ATG5: 11793"
  },
  {
    "caption": "Microscopy-based protein-liposome binding assay as in (B). ATG16L1WT- and ATG16L1LD-GFP immobilised on beads were incubated with rhodamine-labelled, PI3P-positive liposome preparations. Scale bar: 50 μm. Right panel shows quantification of liposome binding relative to ATG16L1WT from 3 independent experiments including SEM values.",
    "ncbi_link": "GFP: 
ATG16L1: 77040"
  },
  {
    "caption": "Protein-protein interaction assay in 293T cells transiently transfected with the indicated S-tagged ATG16L1 constructs. S tag pull down was performed and protein complexes were analysed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "by immunoblotting using the indicated antibodies. Dimerisation assay in 293T cells transiently transfected with ATG16L1-GFP and the indicated S-tagged ATG16L1 constructs and analysed",
    "ncbi_link": "GFP: 
ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- stably expressing the indicated Flag-S-ATG16L1 constructs were amino acid starved for 2 hr prior to immunofluorescence analyses using antibodies against Flag tag (green) and ATG5 (red). Scale bar: 9 μm. Right panels show quantifications of average number of Flag- and ATG5-positive dots per cell.",
    "ncbi_link": "Flag: 
ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- stably expressing the indicated Flag-S-ATG16L1 constructs were amino acid starved for 2 hr prior to immunofluorescence analyses using antibodies against S tag (to detect ATG16L1, red) and WIPI2 (green). Scale bar: 9 μm. Lower panel shows quantification of average number of WIPI2 positive dots per cell.",
    "ncbi_link": "Flag: 
ATG16L1: 77040"
  },
  {
    "caption": "Average intensities of individual Flag-ATG16L1 dots in (A). Underlying grey circles represent individual data points. Dots were quantified (n=1225 for ATG16L1WT; n=334 for ATG16L1LD).",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "WIPI2-/- cells reconstituted with the indicated Flag-S-ATG16L1 constructs were amino acid starved for 2 hr prior to immunofluorescence analyses using antibodies against Flag tag (green) and FIP200 (red). Scale bar: 9 μm. Lower panel shows quantification of average number of Flag positive dots per puncta-positive cell.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
WIPI2: 74781"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LD-expression constructs and autophagy assessed during treatment with various stimuli followed by immunoblotting using the indicated antibodies. Cells were amino acid starved (AA starved) to induce mTORC1-dependent autophagy in the presence or absence of BafA1 for 2 hr prior to lysis.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LD-expression constructs and autophagy assessed during treatment with various stimuli followed by immunoblotting using the indicated antibodies. Mitophagy was induced by CCCP (10 μM) treatment for 6 hr prior to lysis.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LD-expression constructs and autophagy assessed during treatment with various stimuli followed by immunoblotting using the indicated antibodies. Glucose starvation (Glu starved) for 20 hr was used to induce mTORC1-independent autophagy. BafA1 was added to all conditions 2 hr prior to lysis.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LD-expression constructs and autophagy assessed during treatment with various stimuli followed by immunoblotting using the indicated antibodies. LC3-associated phagocytosis (LAP)-like LC3 lipidation was induced by treating cells with CCCP (100 μM) for 2 hr prior to lysis. Right panel shows quantification of LC3-II/LC3-I ratio.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LD-expression constructs and autophagy assessed during treatment with various stimuli followed by immunoblotting using the indicated antibodies. LAP-like LC3 lipidation induced by monensin or ammonium chloride (NH4Cl) for 2 hr prior to lysis.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "ATG16L1-/- cells were reconstituted with ATG16L1WT- or ATG16L1LE-expression constructs and autophagy assessed during amino acid starvation (AA starve) followed by immunoblotting or immunofluorescence analyses. Immunofluorescence analyses of amino acid starved cells (2 hr) using antibodies against WIPI2 (red) or ATG16L1 (green). Scale bar: 9 μm. Cells as in (A) with the addition of 3'MA (and pretreatment with the drug for 30 min). Scale bar: 9 μm.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "WIPI2-/- cells reconstituted with the indicated ATG16L1 constructs were amino acid starved for 2 hr. BafA1 treatment was included in all conditions for 2 hr prior to lysis. Cell lysates were analysed by immunoblotting using the indicated antibodies. Quantification of LC3-II/LC3-I ratio of three independent experiments is shown on the right panel.",
    "ncbi_link": "ATG16L1: 77040
WIPI2: 74781"
  },
  {
    "caption": "Ferroptosis assay in ATG16L1-/- cells stably expressing ATG16L1WT, ATG16L1LD or ATG16L1LE. Cells were cultured in amino acid free media (AA starve) in the presence of 10% FBS or 10% dialysed FBS (diFBS) for 24 hr. Quantification of percentage of PI-positive cells from at least three independent experiments is shown.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "(B) Charged  tRNA levels in mock-injected and AnsB-overexpressing embryos at 6 hpf. Total and charged tRNAs were measured by  qRT-PCR coupled to the OXOPAP assay. The relative charged tRNA level in mock-injected  embryos were set to one. Data information bar charts show the average of three independent biological replicates. Error bars show SD. Individual data points are shown as dots. P-values were calculated using two-sided Student's t-test.",
    "ncbi_link": "AnsB: 947454"
  },
  {
    "caption": "(G) qRT-PCR analysis of hCMV uORF2  reporter mRNA levels in MZznf598 embryos at 6 hpf relative to 2 hpf. (H)  qRT-PCR  analysis of hCMV uORF2  reporter mRNA levels in wild-type  embryos, MZznf598 embryos and MZznf598 embryos injected with a mRNA encoding Myc-tagged full-length (full) or RING domain deleted (∆RING)  Znf598. mRNA levels at 6 hpf relative to 2 hpf are shown. Data information: bar charts show the average of three independent biological replicates. Error bars show SD. Individual data points are shown as dots. P-values were calculated using two-sided Student's t-test.",
    "ncbi_link": "Myc: 
znf598: 407728
Znf598: 407728"
  },
  {
    "caption": "(J) Results of PACE in MZznf598 zebrafish embryos. Black circles show the relative stability of the reporter mRNAs (averages of two biological replicates) in MZznf598 embryos. Gray circles show the relative stability of reporter mRNAs in wild-type embryos The stability of a codon-tag reporter with a UGA  stop codon was set to one. Error bars represent maximum and minimum data points. The relative effect of each codon on mRNA stability in wild-type embryos is shown as a color gradient from red (destabilizing) to blue (stabilizing).",
    "ncbi_link": "znf598: 407728"
  },
  {
    "caption": "(B) Results of the tandem  ORF assay  with Lys AAG×8 and  Lys AAA×8 sequences. (C) Results of the  tandem ORF assay with  Gly×8 and Pro×8 sequences. (D) Results of the tandem  ORF assay  with Asn AAC and Asn AAU  codon tags. (E) Results of the tandem  ORF assay using EGFP ORFs with different codon optimalities. Data information: normalized Fluc activity with no insert was set to one. All experiments were repeated three times, and the average Fluc activity is shown as bar charts. Error bars show SD. Individual data points are shown as dots. P-values were calculated using two-sided Student's t-test.",
    "ncbi_link": "EGFP: 
Fluc: "
  },
  {
    "caption": "(C) SFB  tagged PAF1, SFB-LEO1, SFB-CTR9, SFB-CDC73, SFB-RTF1, SFB-WDR61   along with Myc SHP-1  or Myc PTPN7  were transfected in 293T  cells and interaction  of  SHP-1 with PAF complex components was detected by immunoblotting  with Myc  antibody after S protein beads pulldown  in presence of TurboNuclease.",
    "ncbi_link": "Myc: 
SHP-1: 5777
PTPN7: 5778"
  },
  {
    "caption": "(D) SFB  empty vector, SFB SHP-1 or SFB PTPN7  was co-transfected with Myc  tagged H2B  in 293T  cells. The interaction  of H2B  with  SHP-1 was detected through immunoblotting  using Myc  antibody after  pull down  with streptavidin sepharose  beads.",
    "ncbi_link": "Myc: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
SHP-1: 5777
PTPN7: 5778"
  },
  {
    "caption": "(A) Nuclear  extracts of WT and SHP-1  knockout cells (derived from two independent guide RNAs) were made and the levels of H2BUb  were detected.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(B) Wild type (WT) 293T  cells along with SHP-1 KO cells transfected with either Myc  vector, Myc SHP-1 ∆SH2 or Myc SHP-1 NLS mutant were lysed.  H2BUb levels were determined using specific antibody.",
    "ncbi_link": "Myc: 
SHP-1: 5777"
  },
  {
    "caption": "(C) WT and SHP-1 KO 293T  cells transfected with Myc  vector, Myc SHP-1 or Myc SHP-1  C/S (C453S) mutant were lysed. H2BUb levels were determined using specific antibody.",
    "ncbi_link": "Myc: 
SHP-1: 5777"
  },
  {
    "caption": "(D) H2B  WT along with the indicated Y/F and Y/D mutants were transfected into 293T  cells. Histone extract was prepared from cells transfected with each construct and subjected to western blotting  with anti-H2B  and anti-H2BUb  antibodies.",
    "ncbi_link": "H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341"
  },
  {
    "caption": "(D) 293T  cells were transfected with vector, Myc  tagged  SHP-1  WT or C/S mutant. The phosphorylation  status of endogenous H2B  was detected by immunoblotting  with pY121-H2B  antibody.",
    "ncbi_link": "Myc: 
SHP-1: 5777"
  },
  {
    "caption": "(E) Nuclear  extracts of 293T  WT and SHP-1 KO cells were made and the levels of H2B phosphorylation  were detected using pY121-H2B  antibody.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(F) Wild type (WT) along with SHP-1 KO 293T  cells transfected with either Myc  vector, Myc SHP-1 or Myc SHP-1 C/S mutant were lysed. Levels of pY121-H2B  and H2BUb were determined using specific antibodies.",
    "ncbi_link": "Myc: 
SHP-1: 5777"
  },
  {
    "caption": "MCF7  cells were transduced with (H) CTR9  shRNA along with control shRNA. Post 72 h, cells were collected and lysed to isolate soluble  and nuclear  fractions. Levels of phosphorylated  and ubiquitinated H2B  were detected by immunoblotting  with indicated specific antibodies.",
    "ncbi_link": "CTR9: 9646"
  },
  {
    "caption": "MCF7  cells were transduced with (I) Paf1  shRNA, along with control shRNA. Post 72 h, cells were collected and lysed to isolate soluble  and nuclear  fractions. Levels of phosphorylated  and ubiquitinated H2B  were detected by immunoblotting  with indicated specific antibodies.",
    "ncbi_link": "Paf1: 54623"
  },
  {
    "caption": "MCF7  cells were transduced with (J) RTF1  shRNA along with control shRNA. Post 72 h, cells were collected and lysed to isolate soluble  and nuclear  fractions. Levels of phosphorylated  and ubiquitinated H2B  were detected by immunoblotting  with indicated specific antibodies.",
    "ncbi_link": "RTF1: 23168"
  },
  {
    "caption": "(A) Cell lysates derived from 293T  cells transfected with empty vector, SFB-tagged H2B, H2B  Y121F or H2B  Y121D constructs were pulled down with S-protein agarose  beads. RNF20 interaction with H2B   was detected by immunoblotting  with specific antibody.",
    "ncbi_link": "SFB: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341"
  },
  {
    "caption": "(B) HEK293T  cells were co-transfected with the SFB-tagged H2B, H2B  Y121F or H2B  Y121D constructs along with Myc-tagged UBE2A. Cell lysates were pulled down with S-protein beads, and interaction  was detected by immunoblotting  with Myc  antibody.",
    "ncbi_link": "Myc: 
SFB: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
UBE2A: 7319"
  },
  {
    "caption": "(E) WT 293T  cells along with  SHP-1 KO were co-transfected with SFB  vector or SFB H2B  along with Myc UbE2A. Cell lysates were pulldown  using S-protein  beads, and interaction  of UBE2A  with H2B  was determined by Western blotting with the indicated antibodies.",
    "ncbi_link": "Myc: 
SFB: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
SHP-1: 5777
UbE2A: 7319"
  },
  {
    "caption": "(F) HEK293T  cells were transfected with SFB  vector or SFB H2B  along with Myc UBE2A.Cells were treated with SHP-1  inhibitor TPI  (50nm) for 1hr after 24hrs of transfection. Cells lysates were subjected to pull-down  with S-protein beads, and western blotting was performed using specific antibodies.",
    "ncbi_link": "Myc: 
SFB: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
UBE2A: 7319"
  },
  {
    "caption": "(D) Nuclear  extracts of MCF-7  WT and SHP-1 knockout cells were made and the levels of RNA Polymerase II, RNA Polymerase II Ser2P and RNA Polymerase II  Ser5P were detected by immunoblotting  using specific antibodies.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(F) Nuclear  extracts of MCF-7 WT and SHP-1 knockout cells transfected with Myc  vector, H2B  Y121F or H2B  Y121D constructs were made and the levels of RNA Polymerase II, RNA Polymerase II  Ser2P, RNA Polymerase II  Ser5P and Lamin B1  were detected by immunoblotting  using specific antibodies.",
    "ncbi_link": "Myc: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
SHP-1: 5777"
  },
  {
    "caption": "(G) Immunofluorescence  of WT or SHP-1  knockout MCF7  cells labelled with the  5-Ethynyl Uridine (EU) for 60 minutes to capture nascent RNA  synthesis. Scale bars 10μm. (H) The EU incorporation  in MCF-7  WT and SHP-1 KO cells was quantified in three independent experiments. Values presented as the mean ± SD, ***indicates p<0.001 (One-way ANOVA).",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(C, D) MCF-7  WT cells along with SHP-1  KO cells transfected with either vector, H2B  Y121F or H2B  Y121D mutant were used for ChIP q-PCR  analysis of the H2BUb at indicated genes. The data shown is derived from two independent experiments. Error bars indicate the mean ± SD.",
    "ncbi_link": "H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
SHP-1: 5777"
  },
  {
    "caption": "(A) Lysates of WT and  SHP-1 knockout MCF7  cells were made and the levels of  LC3-I and II were detected by immunoblotting. (B) Levels of LC3 II were normalized against total  LC3 (LC3 I+LC3 II). The data shown is derived from three independent experiments. Error bars indicate the mean ± SD. *p value < 0.05, Student's t-test.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(C) Representative super- resolution images of WT and  SHP-1 KO MCF7  cells immunostained  with LC3  antibody, (Scale bar: 5µm). (D) Quantification of LC3  puncta accumulation per cell done by using ImageJ was shown. Bars represents mean ± SD.(N=60) ***p value < 0.001, Student's t-test.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "(E) WT along with  SHP-1 KO MCF7  cells transfected with either Myc  vector, Myc SHP-1 or Myc SHP-1 NLS mutant were lysed. Levels of LC3  and actin  were determined using specific antibodies.",
    "ncbi_link": "Myc: 
SHP-1: 5777"
  },
  {
    "caption": "(F) WT and  SHP-1 knockout MCF7  cells transfected with the Myc  vector or Myc-tagged H2B, H2B  Y121F or H2B  Y121D constructs were immunostained  with endogenous p62  and Myc  antibody. Image acquisition was done using LSM 700, (Scale bar: 20µm). (G) Accumulation of p62  was quantified by counting p62  positive puncta per cell. (N= 25); values presented as the mean ± SD. ***p value < 0.001 (One-way ANOVA).",
    "ncbi_link": "Myc: 
H2B: 440689///3017///8349///8340///128312///8347///8345///8970///85236///3018///8348///255626///8342///8341
SHP-1: 5777"
  },
  {
    "caption": "(H) Representative super-resolution images of LC3  and LAMP2 immunostaining  in WT and  SHP-1 KO MCF7  cells. (Scale bar: 20 µm for merge & 5 µm for Zoom). (I) LC3  puncta co-localizing  with LAMP2  per cell were quantified using ImageJ. (N=45); values presented as the mean ± SD. ***p value < 0.001, Student's t-test.",
    "ncbi_link": "SHP-1: 5777"
  },
  {
    "caption": "Time course of pyruvate homo-exchange by the Mpc1/Mpc3 hetero-complex in liposomes (n=8) in comparison to empty liposomes (n=6) at a ΔpH of 1.6.",
    "ncbi_link": "Mpc1: 852800
Mpc3: 853158"
  },
  {
    "caption": "Time course of pyruvate homo-exchange by the Mpc1/Mpc3 hetero-complex in physiological pH (n=4) compared to empty liposomes (n=4).",
    "ncbi_link": "Mpc1: 852800
Mpc3: 853158"
  },
  {
    "caption": "In the absence of a ΔpH, the time course of pyruvate homo-exchange was similar for the Mpc1/Mpc3 proteoliposomes and the empty liposomes (n=4).",
    "ncbi_link": "Mpc1: 852800
Mpc3: 853158"
  },
  {
    "caption": "Time course of pyruvate homo-exchange in proteoliposomes at a ΔpH of 1.6 was compared for Mpc3 (n=4), the Mpc1/Mpc3 hetero-complex (n=6) and empty liposomes (n=4).",
    "ncbi_link": "Mpc1: 852800
Mpc3: 853158"
  },
  {
    "caption": "Time course of pyruvate homo-exchange at a ΔpH of 1.6 was compared for Mpc1 (n=4), Mpc1/Mpc3 hetero-complex (n=4) and empty liposomes (n=4).",
    "ncbi_link": "Mpc1: 852800
Mpc3: 853158"
  },
  {
    "caption": "LBPA intensity in a mixed population of cells expressing HRH3-GFP. After transfection with HRH3-GFP, uncloned stably expressing cells (C) were labelled with anti-LBPA antibodies and analysed by automated microscopy (C). Unbiased quantification (D) shows the inverse correlation between HRH3-GFP expression (high expressing cells in green) and the endosome integrated intensity of LBPA staining (high LBPA labelling in red). (n=2 independent experiments with 500,000 cells analysed automatically, error bars = SD).",
    "ncbi_link": "GFP: 
GFP.: 
HRH3: 11255"
  },
  {
    "caption": "LBPA intensity in cells expressing or not HRH3-GFP. HeLa MZ cells stably expressing HRH3-GFP grown in 96-well plates were separately treated, with 4 different siRNAs that target HRH3 (siHRH3#1; siHRH3#2; siHRH3#3; siHRH3#4) or with control non-target (siNT) siRNA (E). HRH3-GFP was analysed by fluorescence microscopy in 4 rows of cells per condition; micrographs are stitched together in the montage. Panel F shows an example of cells treated with siHRH3#2 or siNT, and then labelled with DAPI and antibodies against LBPA. Cells treated as in (E) and labelled with DAPI and antibodies against LBPA as in (F), were analysed by automated microscopy and the integrated intensities of LBPA (left panel) and HRH3-GFP (right panel) signals are compared (G). (n=2 independent experiments with 192 images acquired and analysed automatically, error bars = SD).",
    "ncbi_link": "GFP: 
HRH3: 11255"
  },
  {
    "caption": "Treatment of NPC fibroblasts and NPC null mice with thioperamide. Fibroblast lines obtained from patients with well-established heterozygote mutations in the NPC1 (GM17912 line: NPC1 P1007A / T1036M; GM17911 line: NPC1 I1061T / T1036M) or with a homozygote mutation in the NPC2 gene (GM17910 line: C93F / C93F) were treated or not for 72h with thioperamide 10µM, stained with filipin (cholesterol) and analysed by fluorescence automated microscopy.",
    "ncbi_link": "NPC: 18145
NPC1: 4864
NPC2: 10577"
  },
  {
    "caption": "Effects of thioperamide on cholesterol-dependent transcriptional regulation. The parental HeLa MZ cells, NPC1 KO cells or NPC2 KO cells were treated or not with thioperamide 10 μM for 18h. Total mRNA was extracted and both LDLR mRNA and HMG CoA reductase mRNA were quantified by RT-PCR. (n=3 independent experiments, error bars = SD, one-way ANOVA, *=p<0.05; **=p<0.005)",
    "ncbi_link": "HMG CoA reductase: 3156
LDLR: 3949
NPC1: 4864
NPC2: 10577"
  },
  {
    "caption": "Quantification of cholesterol in NPC null mice by enzymatic analysis. WT or NPC1 null mice were treated or not with thioperamide for 6 weeks after weaning and sacrificed. The total content of unesterified cholesterol in the corresponding liver extracts was then quantified using an enzymatic assay and is expressed in nmol per mg tissue. The total content of LBPA in the same liver extracts was quantified by mass spectrometry (see Appendix Figure S1), and is therefore expressed as a percentage of total phospholipids. The total LBPA content of WT mice was only marginally increased by the drug, either because the doses were low, or because the contribution from tissue material unaffected by the drug obscured selective changes at the cellular level (despite much effort, we were unable to visualize LBPA in liver samples by immunocytochemistry). The relative ratio of LBPA vs. cholesterol values is shown.",
    "ncbi_link": "NPC: 18145
NPC1: 18145"
  },
  {
    "caption": "(C) Clonal cell lines expressing p53-Venus were engineered to monitor p53 expression dynamics ("input") and two canonically regulated p53 target promoters expressing mCherry ("output") in response to Nutlin-3 treatment.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "(A) Representative phase contrast, yellow fluorescent (indicating p53-Venus levels), and red fluorescent (indicating reporter mCherry levels) images at the indicated time points for MDM2 promoter reporter cells exposed to the \"natural dynamics\" Nutlin-3 dosing regimen.",
    "ncbi_link": "mCherry: 
MDM2: 4193"
  },
  {
    "caption": "(B-G) Single cell traces of mCherry expression for the "responding" (light gray) or "not responding" (dark gray) MDM2 promoter or CDKN1A promoter cells exposed to the natural dynamics (B), low amplitude (D), high amplitude (D), high frequency (E), low frequency/short duration (F), or long duration (G) Nutlin-3 dosing regimens. The average trace for responding and not responding cells is shown in red and blue, respectively. Heat maps show alternative representation of all single cell traces below each associated time course plot.",
    "ncbi_link": "mCherry: 
CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "Dose-response curves representing the rate of mCherry expression from the MDM2 (pink dots) and CDKN1A (purple dots) promoters as a function of total p53 levels. Values of expression levels were averaged across all cells in the first 15-h response to the long duration Nutlin-3 dosing regimen. Solid black lines represent the best fit to a Hill function model of promoter activation. Dashed lines indicate the half-maximal threshold of p53 levels for promoter activation and the half maximal promoter activity for each promoter.",
    "ncbi_link": "mCherry: 
CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "(B-G) Effects of p53 duration modulation on target promoter activation in terms of the mean timing (B, E), magnitude (C, F), and rate (D, G) for the MDM2 (B-D) and CDKN1A (E-G) promoters in response to short (light green) and long (dark green) p53 durations. N = at least 45 cells per condition, error bars = SEM.",
    "ncbi_link": "CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "(H) Mean nuclear MDM2-YFP levels in single cells at times corresponding to the first pulse (5.5 h) or second pulse (11 h) of p53 expression in response to natural and long duration Nutlin-3 dosing regimens. N = at least 40 cells per condition, error bars = SEM.",
    "ncbi_link": "YFP: 
MDM2: 4193"
  },
  {
    "caption": "(A) Effects of p53 frequency modulation on target promoter activation in terms of the mean timing (A, D), magnitude (B, E), and rate (C, F) for the MDM2 (A-C) and CDKN1A (D-F) promoters in response to low (light blue), natural (medium blue), high (dark blue) p53 frequencies. N = at least 45 cells per condition, error bars = SEM.",
    "ncbi_link": "CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "(H) Percentage of responding cells for the MDM2 and CDKN1A promoters in response to low, natural, and high frequency p53 pulses.",
    "ncbi_link": "CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "(A) BMDMs were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis (MOI = 10) for 4 h (as described in the Materials and Methods), and then incubated for 24 h (left) or the indicated periods of time (right). Cells were fixed, stained with DAPI to visualize nuclei (blue), and immunolabeled with an anti-LC3 antibody. Primary antibody was detected using an Alexa Fluor 488-conjugated goat anti-rabbit IgG (green). Left: representative immunofluorescence images of LC3 punctae; right: quantification of data (LC3-punctated cells were counted manually). ***p<0.001, vs. Mtb-WT-infected condition. Scale bars, 5 µm. (",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(B) BMDMs were infected with Mtb-Δeis in the absence or presence of 3-methyladenine (3-MA; 10 mM) and subjected to confocal analysis as described in Figure 1A. LC3-punctated cells were counted manually. Each condition was assayed in triplicate, and at least 250 cells were counted in each well. ***p<0.001, vs. SC.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(D) Electron micrographs of Mtb-Δeis-infected BMDMs under low (left) and high (right) magnification show the accumulation of autophagic vesicles (black arrow, initial autophagic vacuoles; white arrow, degradative autophagic vacuoles). Scale bars: 2 µm (left), 0.5 µm (right).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(E) Immunoblot analyses performed using Abs raised to LC3 or β-actin. BMDMs were infected with Mtb-Δeis in the presence or absence of 3-MA (10 mM) or bafilomycin A1 (Baf-A1; 100 nM). Gel images representative of three experiments are shown. The ratio of the intensities of the LC3-II/LC3-I and β-actin bands is indicated below each lane (C and E). UI, uninfected; SC, solvent control (0.1% distilled water (B), 0.1% DMSO (E)).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(A and B) BMDMs were infected with Mtb-WT, Mtb-Δeis or Mtb-c-eis at different MOIs (0.1, 1 and 10) for 18 h (A) or for the indicated periods of time (B; MOI = 10). Supernatants were assessed by ELISA for levels of TNF-α and IL-6. Data (A and B) are presented as the mean±SD of five experiments.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(C and D) BMDMs were stimulated with Mtb-WT, Mtb-Δeis, or Mtb-c-eis for 30 min. Cells were then incubated with 10 µM DHE or 5 µM DCFH-DA for 15 min, washed thoroughly, and immediately analyzed for superoxide or H2O2 production by flow cytometry (C, Left). Cells were labeled with MitoSOX for 30 min and analyzed for mitochondrial ROS levels by flow cytometry (D, top). Quantitative analysis of ROS generation (C, right; D, bottom). *p<0.05, **p<0.01, ***p<0.001, vs. Mtb-WT-infected condition. UI, uninfected.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(A-C) BMDMs were infected with Mtb-Δeis (MOI = 10) for 18 h in the presence or absence of DPI (10 µM), NAC (20 mM), catalase (Cat, 1 mU/mL), or tiron (5 mM). (A) Representative immunofluorescence images (top); percentage of endogenous LC3-punctated cells (bottom)",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(D-F) BMDMs from WT and NOX2 KO mice were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis for 18 h. (D) Numbers of LC3-punctated cells (counted manually) are shown (at least 250 cells were counted in each well).",
    "ncbi_link": "NOX2: 13058
eis: 885903"
  },
  {
    "caption": "(E) Immunoblot analyses performed using Abs raised to LC3 or β-actin. BMDMs from WT and NOX2 KO mice were infected with Mtb-Δeis for 18 h. Gel images representative of three experiments are shown.",
    "ncbi_link": "NOX2: 13058
eis: 885903"
  },
  {
    "caption": "(A) BMDMs were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis (MOI = 10) for the indicated periods of time, washed to remove unbound mycobacteria, and then incubated in complete DMEM at 37°C in 5% CO2. Cell viability was assessed by PI staining and then examined by fluorescence microscopy. (B and C) Experimental conditions were identical to those outlined in panel A. BMDMs were infected with the three strains of mycobacteria for 36 h.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(C) Morphological changes in BMDMs infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis at MOIs of 1 and 10. Representative images are shown. Scale bars: 50 µm (low magnification), 20 µm (high magnification).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(D) Macrophages were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis in the presence or absence of zVAD-fmk (20 µM) or 3-MA (10 mM). Staurosporine (STS; 500 nM) was used as a positive control. After 36 h, cells were stained with PI and then examined by fluorescence microscopy. Data are presented as the mean±SD of at least three separate experiments, each performed in duplicate. *p<0.05, ***p<0.001, vs. Mtb-WT-infected condition (A and B); Mtb-Δeis-infected condition without inhibitors (D). UI, uninfected.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(A and B) BMDMs were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis (MOI = 1) for the indicated periods of time, and then subjected to Western blot analysis using Abs raised to p-ERK1/2, p-p38, p-JNK, and β-actin. Data shown are representative of three independent experiments that all yielded similar results (A). Expression of phospho-MAPK/β-actin protein in cytoplasmic extracts of BMDMs was quantified densitometrically (B).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(C and D) BMDMs were pretreated with U0126 (5, 10, 20 µM), SB203580 (SB; 1, 5, 10 µM), or SP600125 (SP; 5, 10, 20 µM) for 45 min, and then infected with Mtb-Δeis for 30 min (C) or 36 h (D). (C) Cells were then incubated with DHE for 15 min, washed rapidly and thoroughly, and analyzed immediately for superoxide levels by flow cytometry. Quantitative DHE fluorescence data represent the mean±SD of four experiments. (D) Cell death after 36 h was assessed by PI staining and then examined by fluorescence microscopy. (",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(E) Raw264.7 cells were transfected with siRNA specific for JNK1 (siJNK) or a non-specific control siRNA (siNS). At 24 h after transfection, cells were infected with Mtb-Δeis for 36 h. Cell death was then assessed by PI staining, and then examined by flow cytometry. Transfection efficiency was assessed by RT-PCR (inset). Data represent the mean±SD of five random fields and are representative of three independent experiments (D and E). *p<0.05, **p<0.01, ***p<0.001, vs. Mtb-WT-infected condition (B); SC (C and D); siNS (E). UI, uninfected; SC, solvent control (0.1% DMSO).",
    "ncbi_link": "eis: 885903
JNK1: 26419"
  },
  {
    "caption": "C57BL/6 mice were challenged, by aerosol, with 10-30 CFU Mtb-WT, Mtb-Δeis, or Mtb-c-eis and sacrificed 4 weeks post-infection. (A) High- and low-magnification electron micrographs of lung tissue sections from mice infected with Mtb-Δeis show accumulation of autophagic vesicles (black arrow, bacteria in autophagic vacuoles; white arrow, degradative autophagic vacuoles). Scale bars: 2 µm (left upper), 0.5 µm (right). Numbers of autophagic vacuoles per cell in each TEM section (left lower) (mean±SD; n = 50).",
    "ncbi_link": "C57BL/6: 
eis: 885903"
  },
  {
    "caption": "(B) Quantitative RT-PCR analysis of lung tissue from Mtb-WT-, Mtb-Δeis-, and Mtb-c-eis-infected mice. Total RNA was extracted from paraffin-embedded lung tissue sections, as described in the Materials and Methods.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(C) To assess in vivo cell death, bronchoalveolar lavage fluid cells from Mtb-WT-, Mtb-Δeis-, and Mtb-c-eis-infected mice were subjected to PI staining, and analyzed by flow cytometry. Data are presented as the mean±SEM (n = 4).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(D) Numbers of CFUs in lung and spleen 4 weeks after infection with Mtb-WT, Mtb-Δeis, or Mtb-c-eis. Data are presented as log10 CFU±SEM (n = 4).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(E) BMDMs were infected with Mtb-WT, Mtb-Δeis, or Mtb-c-eis and then analyzed by CFU assay. CFU data represent the mean±SD of four individual experiments. **p<0.01, ***p<0.001, vs. Mtb-WT-infected condition. UI, uninfected.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(A) Intracellular superoxide production was analyzed by flow cytometric analysis. BMDMs were infected with Mtb-Δeis (MOI = 10) in the presence or absence of recombinant Eis protein (rEis; 5, 10, 20 µg/mL) or 30 kDa Mtb antigen (30 k; 5, 10, 20 µg/mL). Upper, representative flow cytometric analysis; lower, quantitation of superoxide generation.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(B) THP-1 cells were transfected with mock, Eis-WT, or Eis-ΔAT constructs, and infected with Mtb-Δeis for 30 min. Cells were stained with DHE (for superoxide) or DCFH-DA (for H2O2) and subjected to flow cytometric analysis. Inset, transfection efficiency.",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "(E and F) THP-1 cells transfected with mock, Eis-WT, or Eis-ΔAT constructs were pretreated with SP600125 (SP; 20 µM) or SB203580 (SB; 5 µM) for 45 min before infection with Mtb-Δeis for 30 min (E) or 18 h (F). E, Intracellular superoxide production was analyzed by flow cytometric analysis. F, ELISA analysis for TNF-α and IL-6 levels. Data are presented as the mean±SD of three experiments. **p<0.01, ***p<0.001, vs. SC (A, C, E, and F); mock control (B and D). UI, uninfected; SC, solvent control (0.1% DMSO).",
    "ncbi_link": "eis: 885903"
  },
  {
    "caption": "A. Ig sequence diversification in wild type and h3.3. Each line represents an IGVLR gene from a population cells that have expanded for 36 divisions after cloning. Blue bars = gene conversions; green lollipops = point mutations; green bars = ambiguous mutations (Sale et al, 2001).B. Quantification of sequence diversification in wild type and two h3.3 clones expressed as unique events (gene conversions or point mutations) per kb per generation. (Sequences analysed: WT n = 142, for h3.3 c20 n = 140, for h3.3 c32 n = 190).",
    "ncbi_link": "IGVLR: 426939
h3.3: 427887///396233"
  },
  {
    "caption": "C. Quantification of endogenous AID mRNA in wild type and h3.3 cells. The graph represents the mean and SD of four independent RNA extractions of wild type and h3.3c20. p value calculated with the unpaired T test.",
    "ncbi_link": "AID: 418257
h3.3: 427887///396233"
  },
  {
    "caption": "D. Fluctuation analysis for the formation of sIg-loss variants in wild type (black circles) and h3.3 clones (black diamonds) and in two wild type clones (blue circles), two h3.3 clones (blue diamonds) expressing hAIDup (Wang et al, 2009) at 15 - 20 times the level of wild type AID. The final column shows h3.3 cells with hAIDup complemented with H3.3 (blue triangles). Clones were expanded for 36 cell divisions at which point the percentage of sIgM negative cells in each population was determined by flow cytometry. Error bars represent mean and 1 S.D. P values calculated with the Mann-Whitney test.",
    "ncbi_link": "AID: 418257
H3.3: 427887///396233
h3.3: 427887///396233"
  },
  {
    "caption": "E. Ig sequence diversification in wild type, h3.3 and complemented h3.3 cells overexpressing hAIDup. Key as in (A) plus * = deletion or duplication.",
    "ncbi_link": "AID: 418257
h3.3: 427887///396233"
  },
  {
    "caption": "F. Mutation rate as a function of hAIDup expression in wild type and h3.3. Filled symbols represent clones overexpressing hAIDup, open symbols clones with natural AID expression. Linear regression lines are shown.",
    "ncbi_link": "AID: 418257
h3.3: 427887///396233"
  },
  {
    "caption": "B. Diversification in wild type and h3.3 cells expressing similar levels of hAIDup and UGI. Red lollipops = transitions at C/T; Black lollipops = other point mutations; blue bars = gene conversions.",
    "ncbi_link": "AID: 418257
h3.3: 427887///396233"
  },
  {
    "caption": "C. Mutation rate as a function of hAIDup expression in UGI-expressing wild type and h3.3 cells. Each clone was expanded for 36 cell divisions and hAIDup expression determined by qPCR during the last week of culture.",
    "ncbi_link": "AID: 418257
h3.3: 427887///396233"
  },
  {
    "caption": "A. Enrichment of H3.3 in the rearranged allele of the Ig light chain (IGVLR) compared with the unrearranged allele (IGVLUR). Each bar represents the mean of 3 independent ChIPs each assayed with 3 repeat qPCRs (**** = p<0.0001, unpaired T-test).",
    "ncbi_link": "IGVLR: 426939
IGVLUR: 426939"
  },
  {
    "caption": "B. Igλ mRNA levels in wild type and h3.3 cells determined by qPCR, normalised to EF-1α expression and to WT. n = 3 (ns = not significant, unpaired T-test).",
    "ncbi_link": "EF-1α: 
h3.3: 427887///396233
Igλ: 416928"
  },
  {
    "caption": "C. Surface Ig (sIg) in multiple clones of wild type (blue) and h3.3 (red) cells. Green = unstained control.",
    "ncbi_link": "h3.3: 427887///396233"
  },
  {
    "caption": "D. ChIP for H3K4me3 and H3K36me3 in IGVLR and IGVLUR. Each bar represents the mean of 3 ChIPs for H3K4me3 and IgG and 2 for H3K36me3, each assayed with 3 qPCR repeats (statistical analysis as in Panel A).",
    "ncbi_link": "IGVLR: 426939
IGVLUR: 426939"
  },
  {
    "caption": "E. 4sUDRB mapping of transcription kinetics through IGVL. Representative locations of qPCR amplicons (blue) are shown relative to the TSS of IGVL (distance is shown in parenthesis). qPCR signals were normalised to the enrichment at time zero (before release). Error bars represent 1SD of qPCR triplicates.",
    "ncbi_link": "IGVL: 426939"
  },
  {
    "caption": "A. DNA-RNA hybrids in IGVL and IGCL in wild type and h3.3. The DRIP signal is normalised to total input and to wild type IgVλ (*** = p<0.001, ns = not significant, unpaired T-test).",
    "ncbi_link": "IgVλ: 
IGCL: 426939
IGVL: 426939
h3.3: 427887///396233"
  },
  {
    "caption": "B. MNase mapping reveals that loss of H3.3 does not affect average Igλ nucleosome positioning. The red bars indicate the qPCR amplicons for the MNase mapping. The qPCR signals are normalised to the first amplicon at the TSS. Error bars represent 1SD of 2 experimental repeats.",
    "ncbi_link": "H3.3: 427887///396233
Igλ: 416928"
  },
  {
    "caption": "C. DNA-RNA hybrids in IGVL of wild type clones either without overexpression of RNAseHI (red, clones 1 and 2, each assayed with three qPCR repeats) or with overexpression of RNAseHI (blue, clones 3 and 4, each assayed with three qPCR repeats) (*** = p<0.001, ** = p < 0.01; unpaired T-test). Expression of hAIDup-FLAG and chickenRNAseHI-YFP in these clones is shown in Figure EV6.",
    "ncbi_link": "AID: 418257
IGVL: 426939
RNAseHI: 395848"
  },
  {
    "caption": "D. Rate of Ig diversification in wild type cells with and without overexpression of RNAseHI.",
    "ncbi_link": "RNAseHI: 395848"
  },
  {
    "caption": "A. Location of ssDNA tracts ≥ 8nt in IGVL in wild type (WT) and h3.3 cells detected by bisulphite sequencing. Data is from three independent experiments, the results from each being shown as black, red and green bars respectively. ssDNA on the coding strand is shown above the marker line (numbered relative to the TSS at 0) and on the template strand below. In the centre, the percentage of G and C bases on the coding strand in a 30 bp rolling average window is shown.B. Quantitation of the bisulphite detection of single stranded DNA in wild type, h3.3 and h3.3 complemented cells, normalised to wild type. p-values calculated with a  test. Sequences analysed: Wild type n = 322, h3.3n = 320 and h3.3 + H3.3 n = 95.",
    "ncbi_link": "IGVL: 426939
h3.3: 427887///396233
H3.3: 427887///396233"
  },
  {
    "caption": "C. Bisulphite detection of single stranded DNA in wild type cells with and without RNAseHI overexpression. p-value calculated with a chi‐square test. Sequences analysed: RNAseH1+ve n = 94, RNAseH1-ve n = 90.",
    "ncbi_link": "RNAseHI: 395848"
  },
  {
    "caption": "A Cell viability as assessed by GFP expression in HEK293T cells transfected with the pRetroX TETOne3G-eGFP plasmid only (vector) or pRetroX TETOne3G-eGFP harbouring the N-terminal fragment of GSDMD. Cells were treated with the indicated concentrations of doxycycline 24 h post transfection and the percentage of GFP-positive cells was determined 16 h later by flow cytometry.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "B LDH release from HEK293T cells transfected with the pRetroX TETOne3G-eGFP plasmid only (vector) or pRetroX TETOne3G-eGFP harbouring the N-terminal fragment of GSDMD. At 24 h post transfection, cells were treated with the indicated concentrations of doxycycline for 8 h and the percentage of LDH release was determined. Graphs show mean and s.d. of quadruplicate wells.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "C-D. PI staining of and LDH release from HEK293T cells transfected pRetroX TETOne3G-eGFP harbouring the N-terminal fragment of GSDMD in the presence of osmoprotectants. At 24 h post transfection, PEGs of the indicated molecular weights were added to a final concentration of 30 mM, cells were treated with 250 ng/ml doxycycline for 8 h and the level of PI staining (C) or LDH release (D) was determined.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "A-I. Dye release time courses from liposomes as a percentage of maximal release. E. Two different sets of reactions, where wild type GSDMD (dark to light orange) and the mutant GSDMDI104N (dark to light blue) were independently incubated at the concentrations of 260, 130 and 65 nM with 5 nM caspase-1 and 400 μM 6-carboxifluorescein-loaded liposomes. The time point of 60 minutes is highlighted by a vertical dashed line.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "A-I. Dye release time courses from liposomes as a percentage of maximal release. F. Dye release at 60 minutes of reaction as a function of GSDMD wild type (dark orange) and GSDMDI104N (dark blue) concentration. Error bars for three independent experiments are shown.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "(A) The transcript level of solo LTR in the wild type and the epcr1 mutant. Error bars are standard deviations of three technical replicates. The experiment was independently performed three times and similar results were obtained.",
    "ncbi_link": "epcr1: 829397"
  },
  {
    "caption": "(B) The developmental phenotype of the epcr1 and epcr2 single mutants and the epcr1/2 double mutant relative to the wild type. Two-week-old seedlings grown on vertical MS medium plates are shown.",
    "ncbi_link": "epcr1: 829397
epcr2: 830344"
  },
  {
    "caption": "(C) The transcript levels of solo LTR, SDC, AtSN1, AtGP1 and AtCOPIA28 in the wild type, epcr1 and epcr2 single mutants, epcr1/2 double mutant, and two individual EPCR1 transgenic lines in the epcr1/2 double mutant background. Error bars are standard deviations of three biological replicates.",
    "ncbi_link": "AtCOPIA28: 
AtGP1: 
AtSN1: 
EPCR1: 829397
epcr1: 829397
epcr2: 830344
SDC: 816276"
  },
  {
    "caption": "(A) The interaction between EPCR1 and ARID2 or ARID3. Arabidopsis plants carrying EPCR1-Flag and ARID2-Myc or ARID3-Myc transgenes were used for co-IP.",
    "ncbi_link": "ARID3: 
Flag: 
Myc: 
ARID2: 826744
EPCR1: 829397"
  },
  {
    "caption": "(B) The interaction between TRB1 and ARID2. Arabidopsis plants carrying TRB1-Flag and/or ARID2-Myc transgenes were used for co-IP.",
    "ncbi_link": "Flag: 
Myc: 
ARID2: 826744
TRB1: 841418"
  },
  {
    "caption": "(C) The interaction between TRB1 and EPCR1. Arabidopsis plants carrying TRB1-Flag and/or EPCR1-Myc transgenes were used for co-IP.",
    "ncbi_link": "Flag: 
Myc: 
EPCR1: 829397
TRB1: 841418"
  },
  {
    "caption": "(A) The developmental phenotype of the arid2/3/4 mutant as compared to the wild type. Two-week-old seedlings grown on MS medium are shown.",
    "ncbi_link": "arid2: 826744"
  },
  {
    "caption": "(B) The developmental phenotype of the pwwp1/2/3+/- mutant as compared to the wild type. One-month-old plants grown in soil are shown.",
    "ncbi_link": "pwwp1: 821075"
  },
  {
    "caption": "The effect of the arid2, arid3, and arid4 mutations on the silencing of solo LTR, SDC, and FWA as determined by qPCR. Showing are results of three biological replicates with standard deviations.",
    "ncbi_link": "arid3: 838684
arid4: 843984
arid2: 826744
FWA: 828658
SDC: 816276"
  },
  {
    "caption": "The effect of the pwwp1, pwwp2, and pwwp3 mutations on the silencing of solo LTR, SDC, and FWA as determined by qPCR. Showing are results of three biological replicates with standard deviations.",
    "ncbi_link": "pwwp2: 841600
pwwp1: 821075
pwwp3: 5008017
FWA: 828658
SDC: 816276"
  },
  {
    "caption": "(E) The effect of the trb1 mutation and the TRB2 knockdown (TRB2-KD) on the silencing of solo LTR, as determined by qPCR (right panel). The transcript level of TRB2 was evaluated to confirm the TRB2 knockdown (left panel). Error bars represent standard deviations of three biological replicates.",
    "ncbi_link": "trb1: 841418
TRB2: 836894"
  },
  {
    "caption": "(B) Heat maps showing differentially transcribed genes and TEs in the arid2/3/4 and epcr1/2 mutants relative to the wild type.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(D) Genome browser snapshots showing the transcript patterns of ROS1 and IBM1 in arid2/3/4 and epcr1/2 relative to the wild type.",
    "ncbi_link": "arid2: 826744
epcr1: 829397
ROS1: 818224
IBM1: 819952"
  },
  {
    "caption": "(E) Effects of arid2/3/4 epcr1/2 on the transcript levels of ROS1 and IBM1-L as determined by qPCR. The expression of ROS1 and the longer version of IBM1 (IBM1-L) was evaluated by qPCR. ACT7 was amplified as an internal control. Bars represent SD from two independent experiments, each with three technical replications.",
    "ncbi_link": "ACT7: 830841
arid2: 826744
epcr1: 829397
ROS1: 818224
IBM1: 819952"
  },
  {
    "caption": "(A) The interaction of EPCR1 with HAM1 and HAM2. EPCR1-Flag transgenic plants were crossed to HAM1-Myc and HAM2-Myc transgenic plants. The progeny were used to evaluate the interaction between EPCR1 with HAM1 and HAM2 by co-IP.",
    "ncbi_link": "Flag: 
Myc: 
EPCR1: 829397
HAM1: 836582
HAM2: 825234///830834"
  },
  {
    "caption": "(B) The interaction of ARID2, ARID3, and ARID4 with HAM1 and HAM2. ARID2-Myc, ARID3-Myc, and ARID4-Myc transgenic plants were crossed to HAM1-Flag and HAM2-Flag transgenic plants and their progeny were used for co-IP.",
    "ncbi_link": "ARID3: 
Flag: 
Myc: 
ARID4: 843984
ARID2: 826744
HAM1: 836582
HAM2: 830834"
  },
  {
    "caption": "(C) The interaction of TRB1 with HAM1 and HAM2. TRB1-Flag transgenic plants were crossed to HAM1-Myc and HAM2-Myc transgenic plants and their progeny were used for co-IP.",
    "ncbi_link": "Flag: 
Myc: 
HAM1: 836582
HAM2: 830834
TRB1: 841418"
  },
  {
    "caption": "(D) The interaction of HDA9 with ARID2, ARID3, and ARID4. ARID2-Myc, ARID3-Myc, and ARID4-Myc transgenic plants were crossed to HDA9-Flag transgenic plants and their progeny were used for co-IP.",
    "ncbi_link": "ARID3: 
Flag: 
Myc: 
ARID4: 843984
ARID2: 826744
HDA9: 823594"
  },
  {
    "caption": "(E) The interaction of HDA6 with EPCR1 and ARID2. EPCR1-Flag and ARID2-Flag transgenic plants were crossed to HDA6-Myc transgenic plants and their progeny were used for co-IP.",
    "ncbi_link": "Flag: 
Myc: 
ARID2: 826744
EPCR1: 829397
HDA6: 836431"
  },
  {
    "caption": "(A) Overlap among H4K5 hyperacetylated regions in the arid2/3/4 and epcr1/2 mutants relative to the wild type. The overlap is significant (P=4.410-78) as determined by hypergeometric test. (B) Metaplot of histone H4K5 acetylation levels of TEs in wild type, arid2/3/4, and epcr1/2 plants. Histone H4K5 acetylation levels are represented by normalized reads that obtained in the H4K5Ac ChIP-seq analysis. TSS represents transcription start site and TTS represents transcription termination site. (C) Boxplot of histone H4K5 acetylation levels of TEs in wild type, arid2/3/4, and epcr1/2 plants. Asterisks indicate that H4K5Ac levels is significantly higher in the arid2/3/4 (P=2.4210-13) and epcr1/2 (P=1.5210-8) mutants than in the wild type as determined by Welch's Two-Sample t-test. Horizontal lines represent the median, and the bottom and top of the box represent the 25th and 75th percentile. The whiskers represent data range within 1.5× of the interquantile range.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(D) The nuclei with condensed, intermediate, or decondensed heterochromatin status, as marked by DAPI staining and H3K27me signals. (E) Percentages of nuclei with condensed, intermediate, or decondensed heterochromatin signals in the wild type and the arid2/3/4 mutant. n=113.",
    "ncbi_link": "arid2: 826744"
  },
  {
    "caption": "(F) Abundance of Pol IV-dependent siRNAs in the epcr1/2, arid2/3/4, nrpd1, nrpe1, and hda6 mutants relative to the wild type [(Mut-WT)/(Mut+WT)] from chromosome 3 of Arabidopsis.",
    "ncbi_link": "arid2: 826744
epcr1: 829397
hda6: 836431
nrpd1: 842605
nrpe1: 818591"
  },
  {
    "caption": "(H) Boxplot showing levels of Pol IV-dependent siRNAs that are up-regulated in the hda6 mutant. Asterisks indicate that siRNA levels in the mutants are significantly (P→0) up-regulated compared to the wild type as determined by paired student t-test. Horizontal lines represent the median, and the bottom and top of the box represent the 25th and 75th percentile. The whiskers represent data range within 1.5× of the interquantile range.",
    "ncbi_link": "hda6: 836431"
  },
  {
    "caption": "(A) Metaplot of CG, CHG, and CHH methylation of genes and TEs in the genomes of wild type, epcr1/2, and arid2/3/4 plants. H indicates C, A, or T.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(B) Metaplot of CG, CHG, and CHH methylation on chromosome 3 of Arabidopsis in wild type, epcr1/2, and arid2/3/4 plants.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(D) Boxplot of DNA methylation in the wild type, nrpe1, epcr1/2, and arid2/3/4 mutants. The hypo-DMRs identified in the nrpe1 mutant was defined as RdDM target loci. Asterisks indicate that DNA methylation is significantly (P<0.001) decreased in the mutants as determined by paired student t-test. Horizontal lines represent the median, and the bottom and top of the box represent the 25th and 75th percentile. The whiskers represent data range within 1.5× of the interquantile range.",
    "ncbi_link": "arid2: 826744
epcr1: 829397
nrpe1: 818591"
  },
  {
    "caption": "(E) Heat maps of CG, CHG, and CHH methylation at RdDM target loci. The hypo-DMRs identified in the nrpe1 mutant were defined as RdDM target loci and analyzed in the wild type, nrpe1, eprc1/2, and arid2/3/4 mutants. Black and light yellow indicate low methylation and high methylation, respectively.",
    "ncbi_link": "arid2: 826744
eprc1: 829397
nrpe1: 818591"
  },
  {
    "caption": "(A) Scatter plots showing the effect of the epcr1/2 and arid2/3/4 mutations on CG, CHG, and CHH methylation at the co-upregulated TEs and genes in the epcr1/2 and arid2/3/4 mutants. TE methylation and gene DNA methylation refer, respectively, to methylation of the TE body and methylation of the 1-kb-gene-promoter region.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(B) Box plots of CG, CHG, and CHH methylation in the wild type, arid2/3/4, and epcr1/2 mutants at the co-upregulated TEs and genes in the arid2/3/4 and epcr1/2 mutants. Asterisks indicate statistical significance as determined by paired student t test. CHG methylation of co-upregulated TEs is significantly increased in arid2/3/4 (P=1.2610-4) and epcr1/2 (P=6.310-9); CHH methylation of co-upregulated genes is significantly decreased in arid2/3/4 (P=3.510-6) and epcr1/2 (P=6.410-7). Horizontal lines represent the median, the bottom and top of the box represent the 25th and 75th percentile. The whiskers represent data range within 1.5× of the interquantile range.",
    "ncbi_link": "arid2: 826744
epcr1: 829397"
  },
  {
    "caption": "(C) Overexpression of DRD1 fails to restore the silencing of EPCR1/2 target loci in the epcr1/2 mutant background.",
    "ncbi_link": "epcr1: 829397
EPCR1: 829397
DRD1: 816136"
  },
  {
    "caption": "Live imaging of histone-GFP (green) and ParB-mCherry (magenta) expressed in larval salivary gland nuclei using 1151-Gal4. H3.3-GFP levels are increased at the E(spl)-C in the presence of constitutively active Notch, NΔECD (Notch-ON), compared to control Notch-OFF nuclei expressing LacZ (A). ParB-mCherry binds to its cognate int DNA sequence inserted within the E(spl)-C [8,64]. Yellow dotted box contains E(spl)-C and yellow arrow indicates position of E(spl)-C on chromosome. Scale bars (white) = 5 µm. Quantifications of relative fluorescence intensity of histone-GFP and ParB-mCherry across the E(spl)-C in Notch-OFF (upper) and Notch-ON (lower) conditions. Mean+/-SEM; nnuclei = 7, 6, 5, 8, 9, 11 and nglands = 5, 5, 5, 5, 5, 4 where each gland represents a biological replicate (from top to bottom).",
    "ncbi_link": "Gal4: 
GFP: 
LacZ: 
mCherry: 
ParB: 
histone: 318847///3771792///3772189///3771959///3772032///3772149///3772163///3772173///3772191///3772198///3772231///3771771///3772374///3771729///3772607///3772619///3772517///3772552///3771723///3772370///3772421///3772489///3772518"
  },
  {
    "caption": "Live imaging of histone-GFP (green) and ParB-mCherry (magenta) expressed in larval salivary gland nuclei using 1151-Gal4. E(spl)-C in the presence of constitutively active Notch, NΔECD (Notch-ON), compared to control Notch-OFF nuclei expressing LacZ but there is little change in H3-GFP between Notch-OFF and Notch-ON nuclei ParB-mCherry binds to its cognate int DNA sequence inserted within the E(spl)-C [8,64]. Yellow dotted box contains E(spl)-C and yellow arrow indicates position of E(spl)-C on chromosome. Scale bars (white) = 5 µm. Quantifications of relative fluorescence intensity of histone-GFP and ParB-mCherry across the E(spl)-C in Notch-OFF (upper) and Notch-ON (lower) conditions. Mean+/-SEM; nnuclei = 7, 6, 5, 8, 9, 11 and nglands = 5, 5, 5, 5, 5, 4 where each gland represents a biological replicate (from top to bottom).",
    "ncbi_link": "Gal4: 
GFP: 
LacZ: 
mCherry: 
ParB: 
histone: 318847///3771792///3772189///3771959///3772032///3772149///3772163///3772173///3772191///3772198///3772231///3771771///3772374///3771729///3772607///3772619///3772517///3772552///3771723///3772370///3772421///3772489///3772518"
  },
  {
    "caption": "Live imaging of histone-GFP (green) and ParB-mCherry (magenta) expressed in larval salivary gland nuclei using 1151-Gal4. E(spl)-C in the presence of constitutively active Notch, NΔECD (Notch-ON), compared to control Notch-OFF nuclei expressing LacZ (A). with H3.3core-GFP ParB-mCherry binds to its cognate int DNA sequence inserted within the E(spl)-C [8,64]. Yellow dotted box contains E(spl)-C and yellow arrow indicates position of E(spl)-C on chromosome. Scale bars (white) = 5 µm. Quantifications of relative fluorescence intensity of histone-GFP and ParB-mCherry across the E(spl)-C in Notch-OFF (upper) and Notch-ON (lower) conditions. Mean+/-SEM; nnuclei = 7, 6, 5, 8, 9, 11 and nglands = 5, 5, 5, 5, 5, 4 where each gland represents a biological replicate (from top to bottom).",
    "ncbi_link": "Gal4: 
GFP: 
LacZ: 
mCherry: 
ParB: 
histone: 318847///3771792///3772189///3771959///3772032///3772149///3772163///3772173///3772191///3772198///3772231///3771771///3772374///3771729///3772607///3772619///3772517///3772552///3771723///3772370///3772421///3772489///3772518"
  },
  {
    "caption": "Effects from depleting chromatin remodelers and histone chaperones, as indicated (wide range shown in A, on recruitment of Su(H)-GFP in Notch-ON nuclei (expressing NΔECD) of larval salivary glands. Different OSA RNAi stocks used in C are denoted by (1) and (2). In all conditions except Moira RNAi (A) nuclei exhibit a bright accumulation of Su(H)-GFP at a single locus when imaged live. Scale bars (yellow) = 5 µm. Percentage of Notch-ON nuclei retaining a single clear band of Su(H)-GFP when the indicated RNAi is co-expressed with NΔECD. For each genotype, 5 nuclei from each of 10 glands were scored (50 nuclei total). **** A significant fraction of nuclei lost the fluorescent band when core components of the BRM complex were perturbed; p<0.0001, two-tailed Fisher's exact test calculated using the raw (non-percentage) scoring data.",
    "ncbi_link": "Moira: 41942
OSA: 42130"
  },
  {
    "caption": "Effects from depleting chromatin remodelers and histone chaperones , BRM complex components shown in C), on recruitment of Su(H)-GFP in Notch-ON nuclei (expressing NΔECD) of larval salivary glands. w RNAi is a control and BrmK804R is expression of dominant-negative Brm. Different OSA RNAi stocks used in C are denoted by (1) and (2). , Snr1 RNAi and BrmK804R expression (C), nuclei exhibit a bright accumulation of Su(H)-GFP at a single locus when imaged live. Scale bars (yellow) = 5 µm. Percentage of Notch-ON nuclei retaining a single clear band of Su(H)-GFP when the indicated RNAi is co-expressed with NΔECD. For each genotype, 5 nuclei from each of 10 glands were scored (50 nuclei total). **** A significant fraction of nuclei lost the fluorescent band when core components of the BRM complex were perturbed; p<0.0001, two-tailed Fisher's exact test calculated using the raw (non-percentage) scoring data.",
    "ncbi_link": "Brm: 39744
OSA: 42130
Snr1: 40657"
  },
  {
    "caption": "Chromatin accessibility in Notch-OFF (B) and Notch-ON (NΔECD expression, C) salivary gland nuclei measured by ATAC-qPCR; fold enrichment at the indicated regions compared to a "closed ctrl" region. Expression of dominant-negative Brm, BrmK804R, led to reduced accessibility of E(spl)mβ-HLH and E(spl)m3-HLH enhancer regions in Notch-OFF conditions, and to a more widespread reduction in accessibility in Notch-ON conditions. "Eip78C enh" corresponds to the ecdysone receptor-binding region of the Eip78C enhancer, which is highly accessible but not Notch-responsive; "Rab11 tr" and "Mst87F tr" represent highly and lowly-expressed control genes respectively. Mean +/- SEM; n = 3; * p<0.05 with two-tailed Welch's t-test comparing LacZ and BrmK804R samples.",
    "ncbi_link": "LacZ: 
Brm: 39744
E(spl)m3-HLH: 43156
E(spl)mβ-HLH: 43152
Eip78C: 40345
Mst87F: 41693
Rab11: 42501"
  },
  {
    "caption": "Chromatin accessibility in salivary gland nuclei depleted for Su(H) by RNAi, measured by ATAC-qPCR; fold enrichment at the indicated regions compared to a \"closed ctrl\" region. Accessibility is increased across most of the E(spl)-C compared to controls expressing LacZ. Control primer regions are as in B and C. Mean +/- SEM; n = 3; * p<0.05 with two-tailed Welch's t-test compared to LacZ controls.",
    "ncbi_link": "LacZ: 
Su(H): 34881"
  },
  {
    "caption": "Effect of brm and Snr1 RNAi on brm and Snr1 cDNA levels respectively, measured by reverse transcription-qPCR in Kc167 cells; percentage cDNA compared to GFP RNAi. The knockdowns are highly effective, with only 1-2% of brm and Snr1 cDNA remaining detectable. Mean +/- SEM; n = 3.",
    "ncbi_link": "GFP: 
brm: 39744
Snr1: 40657"
  },
  {
    "caption": "Knockdown of components of the BRM complex reduces Su(H) recruitment both in Notch-OFF (B) and Notch-ON (C) conditions. Fold enrichment of Su(H) occupancy at the indicated positions detected by ChIP, relative to input, in Kc167 cells treated with brm, Snr1 or GFP RNAi as a control. Notch-ON conditions (C) were induced by 30 minutes of EGTA treatment. Mean +/- SEM, n = 3 (B); Mean, n = 2 (C); * p<0.05 with one-tailed student's t-test compared to GFP RNAi control.",
    "ncbi_link": "GFP: 
brm: 39744
Snr1: 40657"
  },
  {
    "caption": "Effect of brm RNAi on E(spl)mβ-HLH (mβ) and E(spl)m3-HLH (m3) induction by Notch activation (EGTA treatment) measured by reverse transcription-qPCR; shown as fold difference to lacZ RNAi control. Mean +/- SEM; n = 3.",
    "ncbi_link": "lacZ: 
brm: 39744
E(spl)m3-HLH: 43156
m3: 43156
E(spl)mβ-HLH: 43152
mβ: 43152"
  },
  {
    "caption": "Effect of Brm dominant-negative on expression of E(spl)mβ-HLH (mβ) and E(spl)m3-HLH (m3) measured by reverse transcription-qPCR. Expression was analyzed in stable cell lines containing pMT-inducible BrmWT or BrmK804R in the absence (left, uninduced) or presence of copper sulfate (right, Cu2+ induced). The response of E(spl)mβ-HLH and E(spl)m3-HLH to Notch activation ("N-On" = EGTA treatment vs. "N-Off" = PBS control) was reduced in the BrmK804R-expressing cells compared to BrmWT-expressing cells, only when induced with copper (right graph). Mean, n = 2 (left); Mean +/- SEM, n = 3 (right); * p<0.05 with one-tailed student's t-test comparing BrmWT and BrmK804R.",
    "ncbi_link": "Brm: 39744
E(spl)m3-HLH: 43156
m3: 43156
E(spl)mβ-HLH: 43152
mβ: 43152"
  },
  {
    "caption": "Knockdown of actin-related subunit, BAP55, reduces Su(H) recruitment in both Notch-OFF (PBS treatment) and Notch-ON (EGTA treatment) conditions. Fold enrichment of Su(H) occupancy at the indicated positions detected by ChIP, relative to input, in Kc167 cells treated with Bap55 or lacZ RNAi as a control. Mean +/- SEM; n = 3; * p<0.05 with one-tailed student's t-test compared to lacZ RNAi control.",
    "ncbi_link": "lacZ: 
Bap55: 36956
BAP55: 36956"
  },
  {
    "caption": "Effect of Bap55 RNAi on E(spl)mβ-HLH (mβ) and E(spl)m3-HLH (m3) expression levels measured by reverse transcription-qPCR in Notch-OFF (PBS treatment) and Notch-ON (EGTA treatment) conditions. Expression level of RpII215 is shown as a control gene. Mean +/- SEM; n = 3; * p<0.05 with one-tailed student's t-test compared to lacZ RNAi control.",
    "ncbi_link": "lacZ: 
Bap55: 36956
E(spl)m3-HLH: 43156
m3: 43156
E(spl)mβ-HLH: 43152
mβ: 43152
RpII215: 32100"
  },
  {
    "caption": "Nucleosome turnover measured by CATCH-IT-qPCR; fold enrichment over input samples compared to Sec15 tr control region. Su(H)-bound enhancers show increased nucleosome turnover in response to Notch signaling. Notch signaling is activated in Kc167 cells by 6 hours of copper induction of pMT-NICD with copper excluded in the control. Positions of E(spl)-C primers are shown in Fig 3A; the remaining primers are control non-Notch-responsive regions. Mean, n = 2.",
    "ncbi_link": "Sec15: 42499"
  },
  {
    "caption": "brm RNAi reduces nucleosome turnover at Notch-responsive regions. CATCH-IT-qPCR results as in A after brm or lacZ RNAi as a control. Mean +/- SEM; n = 5; * p<0.05 with one-tailed student's t-test comparing brm and lacZ RNAi.",
    "ncbi_link": "lacZ: 
brm: 39744"
  },
  {
    "caption": "Brm is required for Notch-responsive nucleosome turnover. CATCH-IT-qPCR results after brm or lacZ RNAi as in B and pMT-NICD expression as in A. Mean +/- SEM; n=3; * p<0.05 with two-tailed student's t-test compared to control (lacZ RNAi Notch-ON bars are compared to lacZ RNAi Notch-OFF bars and brm RNAi bars are compared to their respective lacZ RNAi control bars).",
    "ncbi_link": "lacZ: 
Brm: 39744"
  },
  {
    "caption": "brm RNAi reduces incorporation of histone H3.3. V5 ChIP-qPCR in Kc167 cells after lacZ or brm RNAi treatment in cells with H3-V5 or H3.3-V5 expression induced from the pMT promoter by 3 hours of copper treatment, shown as fold enrichment over input samples. Mean +/- SEM; n = 3. * p<0.05 with two-tailed Welch's t-test compared to lacZ RNAi control.",
    "ncbi_link": "lacZ: 
H3: 
H3.3: 
V5: 
brm: 39744
histone H3.3: 33736"
  },
  {
    "caption": "C Cold response of cytosolic  free Ca2+  concentration in root cells expressing NES-YC3.6. Superimposition of representative normalized ratio variations for wild-type, oscrt3-1, and the complemented transgenic pOsCRT3 root  cells. The rectangle represents the regions of interest (ROIs) for the ratio measurements. The blue background indicates duration of cold treatment. Bar: 50 μm.",
    "ncbi_link": "crt3: 9267167
CRT3: 9267167"
  },
  {
    "caption": "B Yeast two-hybrid analysis to test the OsCRT3-OsCIPK7 interaction. The interactions  between OsCRT3, OsCRT3N, OsCRT3P or  OsCRT3C with  OsCIPK7, OsCIPK7N, OsCIPK7C,  OsCIPK7NAF, or OsCIPK7PPI were verified.",
    "ncbi_link": "CIPK7: 4333514
CRT3: 9267167"
  },
  {
    "caption": "(A-B) Expression patterns (blue stain) of GUS reporter genes driven by the SKM1(A) or SKM2(B) promoter in roots of 5-day-old Col-0seedlings.",
    "ncbi_link": "GUS: 
SKM1: 817121
SKM2: 835702"
  },
  {
    "caption": "(C) Non-complementation of CLE45 insensitivity of the bam3mutant by BAM3expressed under control of the SKM1promoter (7-day-old seedlings; 2 independent transgenic lines per construct are shown).",
    "ncbi_link": "SKM1: 817121
bam3: 827774
BAM3: 827774"
  },
  {
    "caption": "(D) Full CLE45 sensitivity of skm1or skm2 single and double mutant roots (7-day-old seedlings).",
    "ncbi_link": "skm1: 817121
skm2: 835702"
  },
  {
    "caption": "(E) Failure of SKM1 or SKM2 expressed under control of the BAM3 promoter to complement CLE45 insensitivity of the bam3 mutant (7-day-old seedlings; 3 independent transgenic lines per construct are shown).",
    "ncbi_link": "SKM1: 817121
SKM2: 835702
BAM3: 827774
bam3: 827774"
  },
  {
    "caption": "(F) Gap cell frequency in brxsingle or brxmakr5 double mutants (note: gap cells were absent from Col-0 wild type or makr5single mutants). (G) Illustration of gap cells (arrowheads) in developing protophloem sieve element strands (asterisks) of brxsingle or brxmakr5 double mutants.",
    "ncbi_link": "makr5: 835364
brx: 840078"
  },
  {
    "caption": "(D) Expression pattern of GUS reporter gene driven by the MAKR5 promoter in roots of 5-day-old Col-0seedlings. (E) Corresponding transverse sections from different positions along the root meristem.",
    "ncbi_link": "GUS: 
MAKR5: 835364"
  },
  {
    "caption": "(H) Complementation of makr5CLE45 insensitivity by MAKR5expression under control of a promoter specific for developing sieve elements (CVP2), but not by expression under control of a companion cell-specific promoter (SUC2) (7-day-old seedlings; 3 independent transgenic lines per construct are shown).",
    "ncbi_link": "makr5: 835364
MAKR5: 835364
CVP2: 837048
SUC2: 838877"
  },
  {
    "caption": "(B) Expression of truncated MAKR5 fusion proteins under control of the MAKR5 promoter in 5-day-old roots (asterisks: protophloem sieve element strands).",
    "ncbi_link": "MAKR5: 835364"
  },
  {
    "caption": "(C) Close up of protophloem sieve element strands expressing truncated MAKR5-CITRINE fusion proteins under control of the UBQ10 promoter.",
    "ncbi_link": "MAKR5: 835364
UBQ10: 825880"
  },
  {
    "caption": "(D) Failure of truncated MAKR5 fusion proteins to complement CLE45 insensitivity of the makr5 mutant (7-day-old seedlings; 1-2 independent transgenic lines per construct are shown).",
    "ncbi_link": "makr5: 835364
MAKR5: 835364"
  },
  {
    "caption": "(E) Sensitivity of makr5 mutant roots to continuous brassinolide (BL) treatment (7-day-old seedlings).",
    "ncbi_link": "makr5: 835364"
  },
  {
    "caption": "(F) Expression of MAKR5-BKI1 fusion proteins under control of the MAKR5 promoter in roots of 5-day-old makr5 seedlings.",
    "ncbi_link": "MAKR5: 835364
makr5: 835364"
  },
  {
    "caption": "(G) Complementation of CLE45 insensitivity of makr5 roots by BKI1-MAKR5, but not MAKR5-BKI1 fusion protein (7-day-old seedlings; 3 independent transgenic lines per construct are shown).",
    "ncbi_link": "MAKR5: 835364
BKI1: 834284"
  },
  {
    "caption": "(A) Increased expression of BAM3-CITRINE fusion protein under control of the BAM3 promoter in developing protophloem sieve elements (asterisks) of 5-day-old bam3 roots upon CLE45 treatment.",
    "ncbi_link": "bam3: 827774"
  },
  {
    "caption": "(B) Expression of BAM3-CITRINE fusion protein under control of the BAM3 promoter in 5-day-old Col-0 roots or makr5 roots.",
    "ncbi_link": "makr5: 835364"
  },
  {
    "caption": "(C) Expression of MAKR5-GFP fusion protein under control of the MAKR5 promoter in 5-day-old Col-0 or bam3 roots.",
    "ncbi_link": "bam3: 827774"
  },
  {
    "caption": "(D) GUS reporter gene expression driven by the MAKR5 promoter in roots of 5-day-old Col-0seedlings upon CLE45 treatment.",
    "ncbi_link": "GUS: 
MAKR5: 835364"
  },
  {
    "caption": "(E) Expression of MAKR5-GFP fusion protein under control of the MAKR5 promoter in 5-day-old roots upon CLE45 treatment (3 h). Note accumulation of MAKR5-GFP in protophloem sieve elements (magnified) and its dependence on functional BAM3 and CLE45. The frequency of representative observations per total observations is indicated.",
    "ncbi_link": "BAM3: 827774"
  },
  {
    "caption": "(G-H) Accumulation of MAKR5-BKI1 fusion proteins in protophloem cells upon CLE45 treatment. The frequency of representative observations per total observations is indicated. (I-J) Quantification of fusion protein abundance in developing protophloem cells upon expression under control of the MAKR5 promoter, showing mean total fluorescence (I) and plasma membrane to cytosol signal ratio (J).",
    "ncbi_link": "MAKR5: 835364"
  },
  {
    "caption": "(A-D) Cells expressing Rpl5-GFP (A and B) were grown in rich medium (before starvation) and starved in SD-N for the indicated periods (starvation). (A and C, left) Degradation of GFP-tagged proteins was analyzed by anti-GFP blot of whole cell extracts. (right) The ratio between cleaved GFP and full-length protein was quantified for every time point in four independent experiments. a.u., arbitrary unit.",
    "ncbi_link": "Rpl5: 855972"
  },
  {
    "caption": "(A-D) Cells expressing Rpl25-GFP (C and D) were grown in rich medium (before starvation) and starved in SD-N for the indicated periods (starvation). (A and C, left) Degradation of GFP-tagged proteins was analyzed by anti-GFP blot of whole cell extracts. (right) The ratio between cleaved GFP and full-length protein was quantified for every time point in four independent experiments. a.u., arbitrary unit.",
    "ncbi_link": "Rpl25: 853993"
  },
  {
    "caption": "(A-D) Cells expressing Rpl25-GFP (C and D) were grown in rich medium (before starvation) and starved in SD-N for the indicated periods (starvation). (B and D) Cells before starvation or starved for 24 h (starvation) were examined both by fluorescence microscopy and differential interferential contrast (DIC). Note that 100% of wild-type (WT) and mutant cells expressed GFP-tagged proteins in the cytoplasm before starvation. C, cytoplasmic localization; V, vacuolar accumulation; C + V, localization in both cytoplasm and vacuole.",
    "ncbi_link": "Rpl25: 853993"
  },
  {
    "caption": "(A) GFP or Rpl25-GFP were expressed in cells transformed (+) or not transformed (−) with a plasmid encoding 6His-ubiquitin. (top) Expression levels of GFP and Rpl25-GFP in whole cell lysates were verified with anti-GFP blotting. (middle) Purified 6His-ubiquitin conjugates were examined by anti-GFP blotting. (bottom) 6His-ubiquitin expression and efficiency of purification was controlled using an anti-6His antibody. White lines indicate that intervening lanes have been spliced out.",
    "ncbi_link": "Rpl25: 853993
ubiquitin: 850864///853969///854658///850620"
  },
  {
    "caption": "(A) Indicated strains were transformed with plasmids encoding either Rpl25-GFP (Rpl25) or rpl25 K74,75R-GFP (rpl25KR) before the deletion of a genomic copy of RPL25. (top) Comparable expression levels of Rpl25-GFP or rpl25 K74,75R-GFP in whole cell lysates were confirmed with anti-GFP blotting. Purified 6His-ubiquitin-conjugated forms of Rpl25-GFP or rpl25 K74,75R-GFP (middle) and 6His-ubiquitin expression (bottom) were analyzed as in Fig. 2. Ub, ubiquitin.",
    "ncbi_link": "RPL25: 853993
Rpl25: 853993
ubiquitin: 850864///853969///854658///850620"
  },
  {
    "caption": "(B) Wild-type and ubp3Δ cells expressing Rpl25-GFP or rpl25 K74,75R-GFP were starved for the indicated period of time. (C) Degradation of GFP-tagged proteins was analyzed by anti-GFP blot of whole cell extracts, and the ratio between cleaved GFP and full-length protein was quantified for all time points in four independent experiments. a.u., arbitrary units. (D) Localization of GFP-tagged proteins. C, cytoplasmic localization; V, vacuolar accumulation; C + V, localization in both cytoplasm and vacuole",
    "ncbi_link": "Rpl25: 853993
ubp3: 856895"
  },
  {
    "caption": "(A) Wild-type cells expressing Bre5-GFP, Ltn1-Flag, or ltn1-ΔRing-Flag were starved for the indicated periods of time.",
    "ncbi_link": "ltn1: 855289"
  },
  {
    "caption": "(B) Cells were treated for 30 min with 100 µM cycloheximide or 100 µM MG132. Expression of tagged proteins was analyzed by anti-GFP or anti-Flag blotting of whole cell extracts. Five times less extracts were analyzed for ltn1-ΔRing-Flag cells. A nonspecific band served as a loading control. White lanes indicate that intervening lanes have been spliced out. WT, wild type.",
    "ncbi_link": "ltn1: 855289"
  },
  {
    "caption": "(A_B)  In situs on adult brain  sections reveal that (A)  opn4.1  and (B) opn4xb are coexpressed in many  brain domains including the epiphysis cerebri (indicated with E) or pineal. A horizontal line through a representation of the brain  above the  sagittal section indicates the location within the brain. Scale bar: 1.0 mm.",
    "ncbi_link": "opn4.1: 352918
opn4xb: 563080"
  },
  {
    "caption": "(J)  ish  with  asmt  probe on larvae sampled on the 6th dpf at ZT3 shows that asmt  mRNA is confined to the pineal and indicates that the asmt gene is not ectopically expressed in  opn4 dko larvae. The higher asmt mRNA level measured by qPCR in the  opn4 dko therefore points at a defect in the pineal. Note that the  eyes were removed after the  ish for optimal visibility of expression in the brain. Scale bar: 0.5 mm.",
    "ncbi_link": "asmt: 100141344
opn4: 352918"
  },
  {
    "caption": "(N) ish with  ddc probe on wild-type and opn4 dko larvae sampled on the 6th dpf represents ddc expression in pineals. Biological replicates indicated with BR. Scale bar: 0.05 mm (O) Quantification of the adjusted intensity in the pineals from larvae  presented in N, implies a significant higher ddc transcript level in the  opn4 dko  pineal. Data information: boxplot divides the data in quartiles: the box indicates the interquartile range, with the horizontal line in the box denoting the median of the data set, the whiskers extend to the minimum and maximum, and meet the box at the median of the lower (quartile 1) and median of the upper (quartile 3) half of the dataset. Black dots indicate biological replicates O: n=8), the red dot indicates the mean, red error bars indicate the confidence interval (95%), asterisks indicate significance (0.01<p(✱)<0.05, 0.001<p(✱✱)<0.01, p(✱✱✱)<0.001, ns = not significant).",
    "ncbi_link": "ddc: 406651
opn4: 352918"
  },
  {
    "caption": "B RT-PCR on cytoplasmic (C) and nuclear (N) extracts showing the subcellular localization of lnc-SMaRT. RNA was isolated from C2C12 cells after two days of differentiation. GAPDH mRNA and pre-mRNA (pre-GAPDH) were used respectively as cytoplasmic and nuclear controls. Representative results from three independent experiments are shown.",
    "ncbi_link": "pre-GAPDH: 
GAPDH: 14433
lnc-SMaRT: 100043946"
  },
  {
    "caption": "C qPCR analysis of lnc-SMaRT RNA expression in C2C12 cells undergoing differentiation at the indicated time points. The RNA expression levels in qPCR analyses were normalized against GAPDH mRNA and expressed as relative quantities with respect to GM samples set to a value of 1. Data are presented as the mean ± s.e.m. of three biological replicates (dots).",
    "ncbi_link": "GAPDH: 14433
lnc-SMaRT: 100043946"
  },
  {
    "caption": "D qPCR on RNA extracts from C2C12 myoblasts treated with either control siRNAs (si-SCR) or with two different siRNAs against lnc-SMaRT (si-SMaRT-1, si-SMaRT-2) and induced to differentiate for two days. The RNA expression levels in qPCR analyses were normalized against GAPDH mRNA and expressed as relative quantities with respect to GM samples set to a value of 1. Data are presented as the mean ± s.e.m. of three biological replicates (dots). Statistical analysis was performed with ordinary analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. ***P < 0.001.",
    "ncbi_link": "GAPDH: 14433
lnc-SMaRT: 100043946
SMaRT: 100043946"
  },
  {
    "caption": "E Representative immunofluorescence for Myosin Heavy Chain (MHC in red) in combination with DAPI staining (in blue) C2C12 murine myoblasts transfected with either control (si-SCR) or lnc-SMaRT siRNAs (si-SMaRT-1, si-SMaRT-2) fixed after at two days of differentiation. Histograms represent MHC-positive mononucleated cells/total MHC-positive cells ratio and fusion index quantification (F.I.). At least 5 randomly chosen microscope fields of two independent biological samples were analyzed (n>600 cells for each field). Data are presented as the mean. of the two biological replicates (dots).",
    "ncbi_link": "lnc-SMaRT: 100043946
SMaRT: 100043946"
  },
  {
    "caption": "A Gene expression heatmap showing the hierarchical clustering of protein-coding genes whose expression is altered upon lnc-SMaRT depletion. Expression values, calculated as RPKMs, were log2-transformed and mean centered. Only genes with an average RPKM between 10 and 1000 were plotted.",
    "ncbi_link": "lnc-SMaRT: 100043946"
  },
  {
    "caption": "B Volcano plot describing the differential gene expression between si-SCR and si-SMaRT treated C2C12 samples. For each gene, log2 of fold-change versus -log10 of the unadjusted p-value is plotted. Points in red represent differentially expressed genes (FDR adjusted p-value < 0.05).",
    "ncbi_link": "SMaRT: 100043946"
  },
  {
    "caption": "D Western blot on protein extract from control and lnc-SMaRT overexpressing C2C12 stable cell lines collected after one day of differentiation. CASP3 antibody was used. ACTN was used as loading control. Representative results from three independent experiments are shown.",
    "ncbi_link": "lnc-SMaRT: 100043946"
  },
  {
    "caption": "A Localization on the lnc-SMaRT transcript of the two sets of biotinylated probes (Set#1 and Set#2) used for lnc-SMaRT pull-down experiment.",
    "ncbi_link": "lnc-SMaRT: 100043946"
  },
  {
    "caption": "B Left panel: qPCR analysis of lnc-SMaRT enrichment in the RNA pull-down performed in C2C12 cells at day 2 of differentiation (DM2); Set#1 and Set#2 probes were used against lnc-SMaRT together with a control set of probes against LacZ mRNA (LacZ). Data are expressed in percentage of input and presented as the mean ± s.e.m. of three biological replicates (dots). Right panel: Western blot analysis showing the specific enrichment of the DHX36 helicase in lnc-SMaRT pull-down; GAPDH was used as the negative control. Representative results from three independent experiments are shown. ",
    "ncbi_link": "LacZ: 
lnc-SMaRT: 100043946"
  },
  {
    "caption": "C Upper panel: Western blot with DHX36 antibodies on protein extracts from DHX36 RNA immunoprecipitation. Input sample (IN) accounts for 2.5% of the extract. Representative results from three independent experiments are shown. Lower panel: qPCR analysis of lnc-SMaRT enrichment in DHX36 RIP-derived RNA extracts. WBP4 was used as positive control [31], while Neat1 (a lncRNA expressed at comparable level of lnc-SMaRT according to the RNA-sequencing) and Rps7 were used as negative controls. Data are expessed as percentage of input normalized on IgG control, and presented as the mean ± s.e.m. of three biological replicates (dots). ",
    "ncbi_link": "lnc-SMaRT: 100043946
Neat1: 66961
Rps7: 20115
WBP4: 22380"
  },
  {
    "caption": "D RT-PCR validation of Mlx-α, Mlx-β and MLX-γ mRNA enrichment upon the lnc-SMaRT pull-down performed with Set#1 and Set#2 probes; a control set of probes against LacZ mRNA (LacZ) was used as negative control. GAPDH was used as negative control. Input sample (IN) accounts for 10% of the extract. Representative results from three independent experiments are shown.",
    "ncbi_link": "LacZ: 
GAPDH: 14433
lnc-SMaRT: 100043946
Mlx-α: 21428
Mlx-β: 21428
MLX-γ: 21428"
  },
  {
    "caption": "E RT-PCR analysis of Mlx-α, Mlx-β and Mlx-γ mRNA enrichment in DHX36 RIP-derived RNA extracts in samples treated with control siRNA (siSCR, upper panel) or siRNA against lnc-SMaRT (siSMaRT, lower panel). GAPDH was used as negative control. Input sample (IN) accounts for 10% of the extract. Representative results from three independent experiments are shown.",
    "ncbi_link": "GAPDH: 14433
lnc-SMaRT: 100043946
SMaRT: 100043946
Mlx-α: 21428
Mlx-β: 21428
Mlx-γ: 21428"
  },
  {
    "caption": "F Upper panel: Western blot with FLAG antibody on protein extracts from HeLa cells overexpressing the indicated isoforms of FLAG-tagged MLX (MLX-α, MLX-β and MLX-γ) in control condition (CTRL) or in overexpression of lncSMaRT (OE-SMaRT). FLAG-tag has been inserted at the N-terminus of MLX protein isoforms. HPRT was used as loading control. Representative results from three independent experiments are shown. Middle panel: Quantification of FLAG-tagged protein levels normalized on HPRT signals. Data are expressed presented as the mean ± s.d. of three biological replicates (dots). Statistical analysis was performed with two-way ANOVA followed by Bonferroni's multiple comparisons test. ***P < 0.001. Lower panel: RT-PCR analysis of lnc-SMaRT and Mlx expression on RNA extracts from HeLa cells overexpressing the indicated isoforms of flagged-MLX (MLX-α, MLX-β and MLX-γ) in control condition (CTRL) or in overexpression of lncSMaRT (OE-SMaRT). GAPDH was used as loading control. Representative results from three independent experiments are shown. ",
    "ncbi_link": "FLAG: 
flagged: 
GAPDH: 2597
lnc-SMaRT: 100043946
lncSMaRT: 100043946
SMaRT: 100043946
MLX: 21428
Mlx: 21428
MLX-α: 21428
MLX-β: 21428
MLX-γ: 21428"
  },
  {
    "caption": "G Upper panel: Western blot with FLAG antibodies on protein extracts from N2a cells transfected with an empty vector (CTRL) or with a plasmid overexpressing FLAG-tagged MLX-γ (MLX-γ) in control conditions (si-SCR) or in knockdown of DHX36 (si-DHX36). ACTININ was used as loading control. Representative results from three independent experiments are shown. Lower panel: RT-PCR analysis of Mlx-γ expression on the described RNA extracts. GAPDH was used as loading control. Representative results from three independent experiments are shown. ",
    "ncbi_link": "FLAG: 
DHX36: 72162
GAPDH: 14433
MLX-γ: 21428
Mlx-γ: 21428"
  },
  {
    "caption": "A Immunofluorescence for total MLX protein detection (red signal) performed on C2C12 cells treated with siRNAs against Mlx-γ (si-Mlx-γ), lnc-SMaRT (si-SMaRT), DHX36 (si-DHX36) or with a control siRNA (si-SCR). Cells were fixed two days after the switch to differentiation medium. Representative binary images of single confocal planes for MLX immunofluorescence are shown for each treatment. The inserts on the topside of the images sketch the MLX signal peaks in the nuclei (white stars) to highlight the variation of MLX staining in each condition. Dashed lines indicate the edge of the nucleus.",
    "ncbi_link": "DHX36: 72162
lnc-SMaRT: 100043946
SMaRT: 100043946
Mlx-γ: 21428"
  },
  {
    "caption": "A Left panel: schematic representation of the luciferase constructs produced for Mlx. Mlx 5'- and 3'UTR-interacting regions were cloned respectively upstream and downstream the Renilla luciferase coding region (RLuc-Mlx 5'-3') and mutant derivatives devoid of the 5' interacting region (RLuc-Mlx-3') or the 3' UTR interacting region (RLuc-Mlx-5') were obtained. These constructs were co-transfected in C2C12 myoblasts in growth conditions together with plasmids expressing lnc-SMaRT (+) or with a control vector (-). Right panel: Luciferase activity data, presented as the mean ± s.e.m. of three biological replicates (dots), are shown with respect to each RLuc control vector (RLuc-Mlx 5'-3', RLuc-Mlx-3', RLuc-Mlx-5') set to a value of 1. Statistical analysis was performed with ordinary analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. *P < 0.05.",
    "ncbi_link": "luciferase: 
RLuc: 
lnc-SMaRT: 100043946
Mlx: 21428"
  },
  {
    "caption": "B The RLuc-Mlx-5' construct was co-transfected in N2a cells together with plasmids expressing lnc-SMaRT (+) or with a control vector (-) and treated with control siRNA (+) or siRNA against DHX36 (-). Luciferase activity data, presented as the mean ± s.e.m. of three biological replicates (dots), are shown with respect to RLuc-Mlx-5' vector set to a value of 1. Statistical analysis was performed with ordinary analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. **P < 0.01, ***P < 0.001.",
    "ncbi_link": "RLuc: 
DHX36: 72162
lnc-SMaRT: 100043946
Mlx: 21428"
  },
  {
    "caption": "C Left panel: schematic representation of the luciferase constructs used. The RLuc-Mlx-5' construct and its derived mutants (RLuc-Mlxmut30, RLuc-Mlx Δ75) were transfected in N2a cells in growth conditions together with lnc-SMaRT-expressing plasmids (lnc-SMaRT) or with its derived mutant (lnc-SMaRTmut) in the indicated combinations. Right panel: Luciferase activity data, presented as the mean ± s.e.m. of three biological replicates (dots), are shown with respect to each RLuc control vector (RLuc-Mlx-5', RLuc-Mlxmut30, RLuc-Mlx Δ75) set to a value of 1. Statistical analysis was performed with ordinary analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. ***P < 0.001.",
    "ncbi_link": "luciferase: 
RLuc: 
lnc-SMaRT: 100043946
Mlx: 21428"
  },
  {
    "caption": "A Upper panel: schematic representation of the predicted base pairing between lnc-SMaRT (region A) and Mlx γ mRNA; the predicted G-4 structure is boxed in red while the synthetic oligos sequences are underlined in red. Lower panel: Lane 1 and 2: 5 pmol of lnc-SMaRT and Mlx synthetic oligos were loaded on a denaturing polyacrylamide gel and stained for total RNA (SYBR GOLD, indicated as SYBR in the figure). Lane 3 and 4: 5 pmol of lnc-SMaRT and Mlx synthetic oligos were loaded on a native polyacrylamide gel and stained for total RNA (SYBR GOLD). Lane 5 and 6: 200 pmol of lnc-SMaRT and Mlx synthetic oligos were loaded on a native polyacrylamide gel and stained with the selective G-quadruplex staining N-methyl mesoporphyrin IX (NMM). Lane 7 and 8: 5 pmol of Mlx oligo alone (7) or in combination with 5pmol of lnc-SMaRT oligo (8) were heated at 100°C for 10 min and, after slow cooling, loaded on a native polyacrylamide gel and stained for total RNA (SYBR GOLD). Lane 9 and 10: 200 pmol of Mlx oligo alone (7) or in combination with 200 pmol of lnc-SMaRT oligo (8) were heated at 100°C for 10 min and, after slow cooling, loaded on a native polyacrylamide gel and stained with the selective G-quadruplex staining N-methyl mesoporphyrin IX. Asterisk (*) indicates the second NMM-positive band obtained upon SMaRT and γ-oligo interaction. Data information: Representative gels from at least three independent experiments are shown.",
    "ncbi_link": "Mlx γ: 
lnc-SMaRT: 100043946"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying the indicated plasmids were grown to early stationary phase (OD600 of 1.5) and induced with L-arabinose (0.2% final conc.). Expression of MicV and VrrA was monitored on Northern blots. 5S rRNA served as loading control.",
    "ncbi_link": "5S rRNA: 
MicV: 
VrrA: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type, ΔvchM and ΔvchM ΔrpoE strains harboring PmicV::mKate2 plasmids were grown in M9 medium. Samples were collected during various growth phases and analyzed for fluorescence.",
    "ncbi_link": "micV: 
mKate2: 
vchM: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying PmicV::mKate2 plasmids were cultivated in LB to exponential phase (OD600 of 0.4) and treated with ethanol (3.5% final conc.), or water. Fluorescence was determined 180 min after ethanol treatment and mKate2 levels of the mock-treated samples were set to 1.",
    "ncbi_link": "mKate2: 
micV: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying PvrrA::mKate2 (E) plasmids were cultivated in LB to exponential phase (OD600 of 0.4) and treated with ethanol (3.5% final conc.), or water. Fluorescence was determined 180 min after ethanol treatment and mKate2 levels of the mock-treated samples were set to 1.",
    "ncbi_link": "mKate2: 
vrrA: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type, ΔmicV, ΔvrrA or ΔvrrA ΔmicV strains were grown in LB to OD600 of 0.2 and treated with ethanol (3.5% final conc.). After 5h of treatment, serial dilutions were prepared, recovered on agar plates and CFU / ml were determined.",
    "ncbi_link": "micV: 
vrrA: "
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying pBAD-micV, pBAD-vrrA or an empty vector control (pCtr) were cultivated to early stationary phase (OD600 of 1.5) in LB. Cells were treated with L-arabinose (0.2% final conc.) and RNA samples were collected at the indicated time points after induction. Northern blot analysis was performed to determine VrrA, MicV and ompT levels. 5S rRNA served as loading control. For comparison, RNA samples of a wild-type strain carrying pCtr were collected during various growth phases, which indicated ~18-fold and ~7-fold higher levels of VrrA and MicV expressed from the pBAD plasmids, respectively (see Source data for quantifications).",
    "ncbi_link": "micV: 
ompT: 
vrrA: 
5S rRNA: 
MicV: 
VrrA: "
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the indicated reporter plasmids (x-axis) and either an empty vector control (pCtr), the pMicV, or the pVrrA plasmid, were cultivated in M9 and GFP fluorescence was measured. Fluorescence of the control strains was set to 1. The target genes were classified according to (B): regulated by both sRNAs",
    "ncbi_link": "micV: 
vrrA: 
GFP: 
MicV: 
VrrA: "
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the indicated reporter plasmids (x-axis) and either an empty vector control (pCtr), the pMicV, or the pVrrA plasmid, were cultivated in M9 and GFP fluorescence was measured. Fluorescence of the control strains was set to 1. The target genes were classified according to regulated only by MicV",
    "ncbi_link": "micV: 
vrrA: 
GFP: 
MicV: 
VrrA: "
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the indicated reporter plasmids (x-axis) and either an empty vector control (pCtr), the pMicV, or the pVrrA plasmid, were cultivated in M9 and GFP fluorescence was measured. Fluorescence of the control strains was set to 1. The target genes were classified according to regulated only by VrrA",
    "ncbi_link": "micV: 
vrrA: 
GFP: 
MicV: 
VrrA: "
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the ompT::gfp or ompT M1*::gfp fusions (D), ushA::gfp or ushA M1*::gfp fusions (E), or lpp::gfp or lpp M2*::gfp fusions (F) and an empty vector control (pCtr), the micV expression plasmids (pMicV, pMicV M1) or the vrrA expression plasmids (pVrrA, pVrrA M2) were grown in M9 and GFP fluorescence was measured. M1 and M2 denote the mutations indicated in (A, B, C). Fluorescence of the control strains was set to 1.",
    "ncbi_link": "micV: 
ompT: 
vrrA: 
gfp: 
GFP: 
lpp: 
MicV: 
VrrA: 
ushA: 2613310"
  },
  {
    "caption": "V. cholerae ΔrpoE, ΔrpoE ΔvrrA, ΔrpoE ΔmicV or ΔrpoE ΔvrrA ΔmicV strains carrying pBAD-rpoE or an empty vector control (pCtr) were grown to OD600 of 1.5 and L-arabinose (0.2% final conc.) was added. RNA samples were collected at the indicated time points and monitored for ompT (G), ushA (H), or lpp (I) levels using qRT-PCR.",
    "ncbi_link": "lpp: 
micV: 
ompT: 
vrrA: 
ushA: 2613310
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the ompT::3XFLAG gene and pMicV, pVrrA, pRybB, or an empty vector control (pCtr) were cultivated in LB to an OD600 of 2.0. RNA and protein samples were collected and analyzed for MicV, VrrA and RybB expression on Northern blots. OmpT::3xFLAG production was tested on Western blots. RNAPα and 5S rRNA served as loading controls for Western and Northern blots, respectively.",
    "ncbi_link": "micV: 
ompT: 
vrrA: 
5S rRNA: 
FLAG: 
MicV: 
RybB: 
VrrA: "
  },
  {
    "caption": "E. coli wild-type strains carrying pMicV, pVrrA, pRybB, or an empty vector control (pCtr) were grown in LB to an OD600 of 2.0. RNA and protein samples were collected and investigated on Northern blots and SDS-PAGE, respectively. For comparison, we included the E. coli insertional mutant strains ompA::kanR and ompC::kanR for specific assignment of OmpA and OmpC bands.",
    "ncbi_link": "MicV: 
VrrA: 
OmpA: 945571
OmpC: 946716
RybB: 2847774"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying pMicV, pVrrA, pRybB, or an empty vector control (pCtr) were cultivated in LB to OD600 of 0.2 and treated with ethanol (3.5% final conc.). After 5h of treatment, serial dilutions were prepared, recovered on agar plates and CFU / ml were determined.",
    "ncbi_link": "MicV: 
RybB: 
VrrA: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying an empty vector control (pCtr), pRybB, or the sRNA library after consecutive selection experiments (Sel1, Sel2, Sel3) were grown in LB to OD600 of 0.2. Cells were treated with ethanol (3.5% final conc.) for 6 hours. Serial dilutions were prepared and spotted onto agar plates. R1 and R2 indicate two independent biological replicates.",
    "ncbi_link": "RybB: 2847774
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae wild-type and ΔrpoE strains carrying an empty vector control (pCtr), pRybB, or the sRNA library before (input) or after consecutive ethanol selection experiments (Sel1, Sel2, Sel3) were cultivated in LB to OD600 of 2.0. Membrane fractions were analyzed by SDS-PAGE. The indicated bands were analyzed by mass spectrometry.",
    "ncbi_link": "RybB: 
rpoE: 2613009"
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV cells expressing the ompA::3xFLAG gene and carrying an empty vector control (pCtr), or plasmids producing the 15 most highly enriched sRNA variants (sRNA variants 1-15) were grown in LB to an OD600 of 2.0. RNA and protein samples were collected and tested for sRNA and OmpA::3xFLAG expression on Northern and Western blots, respectively (with RNAPα and 5S rRNA as loading controls).",
    "ncbi_link": "micV: 
vrrA: 
5S rRNA: 
FLAG: 
ompA: 2613252"
  },
  {
    "caption": "V. cholerae ΔvrrA ΔmicV strains carrying the ompA::gfp fusion and an empty vector control (pCtr) or the enriched sRNA expression plasmids were grown in M9 and GFP fluorescence was measured. Fluorescence of the control strains was set to 1.",
    "ncbi_link": "micV: 
vrrA: 
gfp: 
GFP: 
ompA: 2613252"
  },
  {
    "caption": "V. cholerae wild-type, ΔrpoE, ΔompA or ΔrpoE ΔompA strains were grown in LB to OD600 of 0.2 and treated with ethanol (3.5% final conc.). After 5h of treatment, serial dilutions were prepared, recovered on agar plates and CFU / ml were determined.",
    "ncbi_link": "ompA: 2613252
rpoE: 2613009"
  },
  {
    "caption": "(A) Immunoblot of HIV-1 GFP virus particles (2×1011 genomes) produced with lopinavir (LPV, 0-100 nM) detecting p24 antibody.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Titration of LPV-treated HIV-1 GFP viruses on PMA-treated THP-1 shSAMHD1 cells. Mean ± SD, n=3.",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": "Titration of LPV-treated HIV-1 GFP viruses on PMA-treated U87 cells. Mean ± SD, n=3.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " ISG qPCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with LPV-treated HIV-1 GFP viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line). ",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": " ISG qPCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with LPV-treated HIV-1 GFP viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line). ",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": " ISG qPCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with LPV-treated HIV-1 GFP viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line). ",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": "PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with LPV-treated HIV-1 GFP viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line). G) CXCL-10 protein in cell supernatants from D-F (ELISA).",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": "(H) ISG qRT-PCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with 0.2 U RT/ml 30 nM LPV-treated HIV-1 GFP in the presence of DMSO vehicle or 2 μM ruxolitinib. A control was stimulated with 1 ng/ml IFNβ.",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": "(I) RT products from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with 0.3 U RT/ml LPV-treated HIV-1 GFP viruses.",
    "ncbi_link": "GFP: 
SAMHD1: 25939"
  },
  {
    "caption": "(A) Immunoblot of HIV-1 GFP virus particles (2×1011 genomes) with varying proportions of ΔCA-SP1 protease cleavage mutation detecting p24.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(B) Titration of HIV-1 GFP ΔCA-SP1 viruses on U87 cells. Mean ± SD, n=3.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(C ISG qRT-PCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with HIV-1 GFP ΔCA-SP1 viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line).",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "D) ISG qRT-PCR from PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with HIV-1 GFP ΔCA-SP1 viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line).",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "PMA-treated THP-1 shSAMHD1 cells transduced for 24 h with HIV-1 GFP ΔCA-SP1 viruses (0.1 U RT/ml red line, 0.5 U RT/ml blue line). E) CXCL-10 protein in supernatants from (C, D) (ELISA).",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "(G) IFIT-1 reporter activity from monocytic THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP ΔCA-SP1 viruses (0.016 - 0.2 U RT/ml). Data are shown as individual measurements, representative of 2 repeats.",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "(H) IFIT-1 reporter activity from monocytic THP-1-IFIT-1 cells transduced with HIV-1 GFP containing either 0 % (WT) or 75 % ΔCA-SP1 mutant, or stimulated with 4 μg/ml cGAMP as a control, in the presence of DMSO vehicle or 2 μM ruxolitinib.",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "(A) IFIT-1 reporter activity from THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP containing 0 % (WT) or 75 % ΔCA-SP1 mutant (1 U RT/ml) in the presence of DMSO vehicle, 5 μM neviripine or 10 μM raltegravir.",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP containing 0 % (WT) or 75 % ΔCA-SP1 mutant (1 U RT/ml) in the presence of DMSO vehicle, 5 μM neviripine or 10 μM raltegravir. B) CXCL-10 protein in supernatants from (A) (ELISA).",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "ISG qRT-PCR from THP-1-IFIT-1 cells transduced for 24 h with 0 % (WT) or 75 % ΔCA-SP1 mutant (109 and 3×109 genomes/ml) in the presence of DMSO vehicle, 5 μM neviripine or 10 μM raltegravir.",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "ISG qRT-PCR from THP-1-IFIT-1 cells transduced for 24 h with 0 % (WT) or 75 % ΔCA-SP1 mutant (109 and 3×109 genomes/ml) in the presence of DMSO vehicle, 5 μM neviripine or 10 μM raltegravir.",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "(E) IFIT-1 reporter activity from THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP containing 0 % ΔCA-SP1 (WT), 75 % ΔCA-SP1, 75 % ΔCA-SP1 carrying a mutation in reverse transcriptase (75 % ΔCA-SP1 RT D185E) or 75 % ΔCA-SP1 carrying a mutation in integrase (75 % ΔCA-SP1 INT D116N) (3.75×109, 7.5×109 and 1.5×1010 genomes/ml).",
    "ncbi_link": "INT: 
integrase: 
reverse transcriptase: 
RT: 
IFIT-1: 3434"
  },
  {
    "caption": "(A) IFIT-1 reporter activity from PMA-treated THP-1-IFIT-1 shSAMHD1 cells lacking STING or MAVS, or a gRNA control (Ctrl) cell line transduced for 24 h with HIV-1 GFP 75 % ΔCA-SP1 (0.4 U RT/ml) or stimulated by transfection with either HT-DNA (0.1 μg/ml) or poly I:C (0.5 μg/ml).",
    "ncbi_link": "GFP: 
IFIT-1: 3434
MAVS: 57506
SAMHD1: 25939
STING: 340061"
  },
  {
    "caption": "IRF reporter activity from PMA-treated THP-1 Dual shSAMHD1 cells lacking cGAS or a matching control (Ctrl) cell line stimulated for 24 h with poly I:C (transfection, 0.5 μg/ml), HT-DNA (transfection, 0.1 μg/ml), LPS (50 ng/ml) or cGAMP (transfection, 0.5 μg/ml)",
    "ncbi_link": "IRF: 
cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "IRF reporter activity from PMA-treated THP-1 Dual shSAMHD1 cells lacking cGAS or a matching control (Ctrl) cell line transduced for 24 h with HIV-1 GFP containing either 0 % (WT) or 75 % ΔCA-SP1 (1×1010 and 2×1010 genomes/ml)",
    "ncbi_link": "IRF: 
cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "PMA-treated THP-1 Dual shSAMHD1 cells lacking cGAS or a matching control (Ctrl) cell line transduced for 24 h with HIV-1 GFP containing either 0 % (WT) or 75 % ΔCA-SP1 (1×1010 and 2×1010 genomes/ml) (C). D) CXCL-10 protein in supernatants from (C) (ELISA). Triangles indicate CXCL-10 not detected.",
    "ncbi_link": "cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "(E) IFIT-1 reporter activity from PMA-treated THP-1-IFIT-1 shSAMHD1 cells lacking STING, MAVS or matching gRNA control (Ctrl) cell line transduced for 24 h with DRV-treated HIV-1 GFP (1×1010 genomes/ml).",
    "ncbi_link": "GFP: 
IFIT-1: 3434
MAVS: 57506
SAMHD1: 25939
STING: 340061"
  },
  {
    "caption": "(F) IRF reporter activity from PMA-treated THP-1 Dual shSAMHD1 cells lacking cGAS or matching control (Ctrl) cell line transduced for 24 h with DRV-treated HIV-1 GFP (1×1010 genomes/ml).",
    "ncbi_link": "GFP: 
IRF: 
cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "PMA-treated THP-1-IFIT-1 shSAMHD1 cells lacking STING, MAVS or matching gRNA control (Ctrl) cell line transduced for 24 h with DRV-treated HIV-1 GFP (1×1010 genomes/ml). G) CXCL-10 protein in supernatants from (E).",
    "ncbi_link": "IFIT-1: 3434
MAVS: 57506
SAMHD1: 25939
STING: 340061"
  },
  {
    "caption": "PMA-treated THP-1 Dual shSAMHD1 cells lacking cGAS or matching control (Ctrl) cell line transduced for 24 h with DRV-treated HIV-1 GFP (1×1010 genomes/ml). (H) CXCL-10 protein in supernatants from (F) (ELISA).",
    "ncbi_link": "cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "(I) IRF reporter activity from PMA-treated THP-1 Dual shSAMHD1 control cells transduced for 48 h with WT, DRV-treated (DRV, 12.5 nM) or HIV-1 GFP containing 90 % ΔCA-SP1 (1×1010 genomes/ml) in the presence of DMSO vehicle, 2 μM ruxolitinib or 0.5 μg/ml H151.",
    "ncbi_link": "IRF: 
SAMHD1: 25939"
  },
  {
    "caption": "Abrogation-of-restriction assay in FRhK4 cells expressing restrictive rhesus TRIM5. FRhK4 cells were co-transduced with a fixed dose of HIV-1 GFP (5×107 genomes/ml) and increasing doses of HIV-LUC ΔCA-SP1 mutants Rescue of GFP infectivity was assessed by flow cytometry. Data are singlet % GFP values and two repeats of the experiment are shown. See also Appendix figure S3. Statistical analyses were performed using 2-way ANOVA with multiple comparisons. * P<0.05, ** P<0.01, *** P<0.001.",
    "ncbi_link": "GFP: 
TRIM5: 574288"
  },
  {
    "caption": "Abrogation-of-restriction assay in FRhK4 cells expressing restrictive rhesus TRIM5. FRhK4 cells were co-transduced with LPV-treated HIV-LUC viruses Rescue of GFP infectivity was assessed by flow cytometry. Data are singlet % GFP values and two repeats of the experiment are shown. See also Appendix figure S3. Statistical analyses were performed using 2-way ANOVA with multiple comparisons. * P<0.05, ** P<0.01, *** P<0.001.",
    "ncbi_link": "TRIM5: 574288"
  },
  {
    "caption": "(A) Infection data for THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (0.1-3 U/ml RT) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (0.1-3 U/ml RT) in the presence of DMSO vehicle or PF-74 (10 μM). B) IFIT-1 reporter activity in supernatant from (A).",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "ISG qRT-PCR from monocytic THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (0.25-1 U/ml RT) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "IFIT-1: 3434"
  },
  {
    "caption": "ISG qRT-PCR from monocytic THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (0.25-1 U/ml RT) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "GFP: 
IFIT-1: 3434"
  },
  {
    "caption": "(E) CXCL-10 protein in supernatants of THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (3 U/ml) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "GFP: 
IFIT-1: 3434"
  },
  {
    "caption": "(F) IFIT-1 reporter activity from THP-1-IFIT-1 cells transduced for 24 h with HIV-1 GFP (3 U/ml RT) in the presence of DMSO vehicle or PF-74 (10 μM) and ruxolitinib (Rux, 2 μM) as indicated.",
    "ncbi_link": "GFP: 
IFIT-1: 3434"
  },
  {
    "caption": "(G) IRF reporter activity from THP-1 Dual shSAMHD1 cells lacking cGAS or a matching control (Ctrl) cell line transduced for 24 h with HIV-1 GFP (3 U/ml and 6 U/ml) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "GFP: 
IRF: 
cGAS: 115004
SAMHD1: 25939"
  },
  {
    "caption": "(H) IFIT-1 reporter activity from THP-1-IFIT-1 cells lacking MAVS or a matching gRNA control (Ctrl) cell line transduced for 24 h with HIV-1 GFP (3 U/ml and 6 U/ml) in the presence of DMSO vehicle or PF-74 (10 μM).",
    "ncbi_link": "GFP: 
IFIT-1: 3434
MAVS: 57506"
  },
  {
    "caption": "F. Representative images of n = 3 of COS7 cells stably expressing GFP-TMD (green) to mark the ER and SiR-lysosome stained LE/Lys (orange) merged. Zoom insets highlight region of interest containing a mobile endosome as denoted by the white arrow. First row represents ER (GFP-TMD) (green), the second row shows MDA generated ER movement (magenta), third row shows a merge of the two preceding channels and the fourth row shows a merge of ER (green) and LE/Lys (orange). Samples were treated with either siControl or siKTN1. Scale bar: 30µm and zoom insets 3µm. All images acquired for 90 frames at 1Hz. Images related to movie EV9 and 10 G. Kymograph of panel (F). H. MDA quantification of panel (F) normalized to control cells, showing the average ER movement surrounding LE/Lys under control or treated conditions and the overall average ER mobility under control or treatment conditions, respectively. Graph represents mean ±s.d. of analyses at multiple locations within the same cell (n=20 cells per condition from 3 independent experiments). Significance two-tailed student t-test. **** P<0.0001; ns = not significant ",
    "ncbi_link": "KTN1: 3895"
  },
  {
    "caption": "E. Representative time-lapse spinning disk confocal images of n = 3 of live COS7 cells stably expressing GFP-TMD (green) and in lower panels transiently expressing mScarlet-RILP (magenta) and SiR-lysosome-stained LE/Lys (orange). Zoom insets shows region of interest containing ER (GFP-TMD). First row represents ER (GFP-TMD) (green), the second row shows MDA-generated ER movement (magenta), third row shows a merge of the two preceding channels. Scale bar: 10µm, zoom insets 3µm. Images related to movie EV19 and movie EV20. Images were acquired for 90 frames at 1Hz. F. MDA quantification of panel (E) and figure EV3A normalized to 1 showing total average ER movement. Graph represents mean ±s.d. of analyses at multiple locations within the same cell (n=15 cells per condition from 3 independent experiments). All images acquired 90 frames at 1Hz. Significance two-tailed student t-test. **** P<0.0001 ns = not significant. ",
    "ncbi_link": "RILP: 83547"
  },
  {
    "caption": "B. Representative stills of spinning disk confocal images of n = 3 of COS7 cells stably expressing TMD-GFP (green) and SiR-lysosome-stained endosomes/lysosomes (orange). COS7 cells in the middle panels overexpress mCherry-RILP (magenta). The COS7 cells in the lower panels overexpress mCherry-TMEM55B (magenta). Zoom insets show region of interest containing the ER (TMD-GFP) (green) and junction analysis of the skeletonized ER where the number of ER junctions representing the quantified average. Scale bars: 15µm. zoom insets: 3µm. C. Quantification of the number of ER junctions per µm2 from panel (B) as resulted from ER junction analysis. Graph represents mean ±s.d. of analyses at multiple locations within one cell (n=15 from 3 independent experiments). Significance two-tailed student t-test. ***P<0.001. ",
    "ncbi_link": "TMEM55B: 90809
RILP: 83547"
  },
  {
    "caption": "A. Representative images of time-lapse spinning disk confocal images of n = 3 of COS7 cells stably expressing GFP-TMD (green) and SiR-lysosome-stained LE/Lys (orange) treated with either siControl or co-treated with siVAPA, siVAPB and siMOSPD2. Zoom insets show regions of interest containing mobile LE/Lys as denoted by the white arrow. First row represents ER (TMD-GFP) (green), the second row shows MDA generated ER movement (magenta), third row shows a merge of the two preceding channels and the fourth row shows a merge of ER (green) and SiR-lysosome stained LE/Lys (orange). Scale bar: 5µm, zoom insets 3µm. Images related to movie EV40 and 47. Images were acquired for 90 frames at 1Hz.",
    "ncbi_link": "MOSPD2: 158747
VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "B. Representative stills of spinning disk confocal images of n = 3 of COS7 cells stably expressing TMD-GFP (green) and SiR-lysosome-stained endosomes/lysosomes (orange) treated with siControl or with siVAPA, siVAPB and siMOSPD2. Zoom insets show region of interest containing ER (TMD-GFP) (green) and junction analysis of skeletonized ER where number of ER junctions representing the quantified average. Scale bars: 10µm. zoom insets: 3µm.",
    "ncbi_link": "MOSPD2: 158747
VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "E, MCF10A control cells and CDC25C-WT/constitutively active mutant CDC25C-S216A over-expressed cells were pretreated with DMSO or AZD6738(250 nM) for 2 hours, and then irradiated with 20 Gy, 24 hours later, cells were harvested for immunoblotting with indicated antibodies.",
    "ncbi_link": "CDC25C: 995"
  },
  {
    "caption": "A, MCF10A Wild-type (WT), cGAS knockout (KO), and STING KO cells were treated with cGAMP at indicated concentrations for 4 hours, and cells were harvested for immunoblotting.",
    "ncbi_link": "cGAS: 115004
STING: 340061"
  },
  {
    "caption": "B, MCF10A WT, cGAS KO, and STING KO cells were transfected with herring testis DNA (HT-DNA, 2 µg/ml) for 6 hours with lipofectamine 3000. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "cGAS: 115004
STING: 340061"
  },
  {
    "caption": "MCF10A WT or two independent clones for cGAS KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "MCF10A WT or two independent clones for STING KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "MCF10A WT or two independent clones for cGAS, STING, and IRF3 KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, except that cells were harvested for real-time quantitative PCR. IFNB1 mRNA level was measured and statistical analyzed by two-way ANOVA (*** means p value < 0.001). Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "cGAS: 115004
IFNB1: 3456
IRF3: 3661
STING: 340061"
  },
  {
    "caption": "MCF10A WT or two independent clones for IRF3 KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "IRF3: 3661"
  },
  {
    "caption": "(A MCF10A WT or two independent clones for MAVS KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies.",
    "ncbi_link": "MAVS: 57506"
  },
  {
    "caption": "MCF10A WT or two independent clones for MAVS, RIG-I KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, (B cells were harvested for real-time quantitative PCR instead of immunoblotting. IFNB1 mRNA level was measured by real-time quantitative PCR. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "RIG-I: 23586
IFNB1: 3456
MAVS: 57506"
  },
  {
    "caption": "C, MCF10A WT or two independent clones for RIG-I KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies.",
    "ncbi_link": "RIG-I: 23586"
  },
  {
    "caption": "D, MCF10A WT or two independent clones for MDA5, KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies.",
    "ncbi_link": "MDA5: 64135"
  },
  {
    "caption": "MCF10A WT or two independent clones for MDA5 KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later E) cells were harvested for real-time quantitative PCR instead of immunoblotting. IFNB1 mRNA level was measured by real-time quantitative PCR. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "MDA5: 64135
IFNB1: 3456"
  },
  {
    "caption": "F) MCF10A WT or two independent clones for IRF7 KO cells were pretreated with DMSO or AZD6738 (250 nM) for 2 hours, and then irradiated with 20 Gy, 3 days later, cells were harvested for immunoblotting with indicated antibodies.",
    "ncbi_link": "IRF7: 3665"
  },
  {
    "caption": "A, 4T1 cells were pretreated with AZD6738 at indicated concentrations for 2 hours, and then irradiated with 10 Gy. 4 days later, Ifnb1 mRNA level was measured by real-time quantitative PCR. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "B, Ifnb1 mRNA levels were measured by real-time quantitative PCR in WT, Sting KO, Mavs KO, and Irf3 KO 4T1 cells. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "Ifnb1: 15977
Irf3: 54131
Mavs: 228607
Sting: 72512"
  },
  {
    "caption": "C, MC38 cells were pretreated with AZD6738 at indicated concentrations for 2 hours, and then irradiated with 20 Gy. 3 days later, Ifnb1 mRNA level was measured by real-time quantitative PCR. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "Ifnb1: 15977"
  },
  {
    "caption": "D, Ifnb1 mRNA levels were measured by real-time quantitative PCR in WT, Sting KO, Mavs KO, and Irf3 KO MC38 cells. Data are presented as mean + standard error of the mean of three biological replicates.",
    "ncbi_link": "Ifnb1: 15977
Irf3: 54131
Mavs: 228607
Sting: 72512"
  },
  {
    "caption": "A, MCF10A WT, cGAS KO, STING KO, and MAVS KO cells were treated with poly(dA-dT)/LyoVec at indicated concentrations for 24 hours. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "cGAS: 115004
MAVS: 57506
STING: 340061"
  },
  {
    "caption": "B, 4T1 WT, Sting KO, Mavs KO, and Irf3 KO cells were treated with poly(dA-dT)/LyoVec at indicated concentrations for 24 hours. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "Irf3: 54131
Mavs: 228607
Sting: 72512"
  },
  {
    "caption": "D, MCF10A WT, MDA5 KO, RIG-I KO, and MAVS KO cells were transfected with AT-rich oligos (2 μg/ml) with LyoVec for 24 hours. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "RIG-I: 23586
MDA5: 64135
MAVS: 57506"
  },
  {
    "caption": "E, MCF10A WT and STING KO cells were transfected with AT-rich and non-AT-rich oligos (2 μg/ml) with lipofectamine 3000 for 4 hours. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "F, 4T1 WT, Sting KO, and Irf3 KO cells were transfected with AT-rich and non-AT-rich oligos (2 μg/ml) with LyoVec for 24 hours. Immunoblotting was performed with indicated antibodies.",
    "ncbi_link": "Irf3: 54131
Sting: 72512"
  },
  {
    "caption": "(a) Proliferation of B cells purified from Atg5f/fCD19-Cre and Atg5f/f control mice and activated for 3 d with LPS, assessed by flow cytometry analysis of dilution of the membrane dye CFSE. (b) Size of B cells purified as in a and activated for various times (horizontal axis) with LPS, assessed by the intensity of forward scatter (FSC) by flow cytometry. (c) CD138 expression of B cells purified and activated as in a. APC, allophycocyanin; PE, phycoerythrin.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(d) Immunoblot analysis of ER proteins in lysates of Atg5f/f and Atg5f/fCD19-Cre B cells 3 d after stimulation with LPS (left), and quantification of band intensity (right; as in Fig. 1c). IgM-H, IgM heavy chain. NS, not significant; *P 0.05 and **P 0.01 (Student's t-test).",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(a) Electron microscopy of Atg5f/f and Atg5f/fCD19-Cre B cells 3 d after stimulation with LPS (left and middle), and quantification of the ER by stereology (right). Scale bars (left and middle), 1 μm.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(c) Quantitative RT-PCR analysis of transcripts encoding spliced XBP-1 (sXBP-1), total XBP-1 (tXBP-1) and BiP in differentiating PCs at 0 d and 3 d after stimulation with LPS, presented relative to that of unstimulated Atg5f/f B cells at day 3.",
    "ncbi_link": "Atg5: 11793
BiP: 14828
XBP-1: 22433"
  },
  {
    "caption": "(d) Quantitative RT-PCR analysis of CHOP mRNA in Atg5f/f and Atg5f/fCD19-Cre B cells stimulated for 3 d with LPS (left and middle), and in Atg5f/f B cells stimulated for 3 d with LPS and treated for the final 24 h with tunicamycin (Atg5f/f 24 h tun; 0.5 μg/ml; positive control), presented relative to that in Atg5f/f B cells stimulated for 3 d with LPS.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478
CHOP: 13198"
  },
  {
    "caption": "(e) Immunoblot analysis (left) of ER proteins in Atg5f/f B cells left untreated (UT) or treated with lysosomal protease inhibitors (10 μM leupeptin and E-64d) for the final 8 h of the third day of LPS-induced differentiation (Leu + E-64d (8 h)). Right, quantification of band intensity (presented as in Fig. 1c). *P 0.05, **P 0.01 and ***P 0.001 (Student's t-test).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Enzyme-linked immunosorbent assay (ELISA) of IgM in supernatants of Atg5f/fCD19-Cre and Atg5f/f B cells stimulated for 3 d with LPS and plated for 4 h (as trypan blue-negative cells at a density of 1 × 106 cells per ml in dedicated media), presented relative to results obtained for Atg5f/f cells.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(b,c) Immunoglobulin assembly (b) and total intracellular (IC) and secreted (Sec) IgM heavy chain (IgM-H, c) in Atg5f/f and Atg5f/fCD19-CreB cells stimulated for 3 d with LPS, then pulse-labeled and chased (time, above lanes), followed by immunoprecipitation of the μ-chain from lysates and SDS-PAGE (left) in nonreducing conditions (b) or reducing conditions (c). Right, quantification of intracellular IgM polymers by densitometry (b) and of secretion efficiency, estimated as the amount of radioactive secreted μ-chain at the end of the chase relative to intracellular μ-chain at the end of the pulse (c). AU, arbitrary units.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(b,c) Immunoglobulin assembly (b) and total intracellular (IC) and secreted (Sec) IgM heavy chain (IgM-H, c) in Atg5f/f and Atg5f/fCD19-CreB cells stimulated for 3 d with LPS, then pulse-labeled and chased (time, above lanes), followed by immunoprecipitation of the μ-chain from lysates and SDS-PAGE (left) in nonreducing conditions (b) or reducing conditions (c). Right, quantification of intracellular IgM polymers by densitometry (b) and of secretion efficiency, estimated as the amount of radioactive secreted μ-chain at the end of the chase relative to intracellular μ-chain at the end of the pulse (c). AU, arbitrary units.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(d) Quantitative RT-PCR analysis of mRNA encoding Blimp-1 and the secreted μ-chain in Atg5f/f and Atg5f/fCD19-Cre B cells stimulated for 3 d with LPS, presented relative to that of Atg5f/f cells.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478
Blimp-1: 12142"
  },
  {
    "caption": "(e) Quantitative RT-PCR analysis of transcripts encoding spliced XBP-1, BiP, Blimp-1 and secreted μ-chain in Atg5f/f B cells stimulated for 3 d with LPS and given no further treatment (−tun) or treated for the final 24 h with tunicamycin (tun 24 h; 0.5 μg/ml), presented relative to results obtained with LPS-stimulated cells given no further treatment. *P 0.05, **P 0.01 and ***P 0.001 (Student's t-test).",
    "ncbi_link": "Atg5: 11793
BiP: 14828
Blimp-1: 12142
XBP-1: 22433"
  },
  {
    "caption": "(a) Intracellular ATP in fresh lysates of Atg5f/f and Atg5f/fCD19-Cre splenic B cells activated for 3 d with LPS (3) or left untreated (0).",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(b) Death of Atg5f/f and Atg5f/fCD19-Cre splenic B cells activated for various times (horizontal axis) with LPS, quantified by flow cytometry by propidium iodide (PI) staining.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(c) Quantitative PCR analysis of genomic DNA in differentiating B cells from Atg5f/f and Atg5f/fCD19-Cre mice, assessing nonrecombinant (Undeleted; left) and recombinant (Deleted; right) loxP-flanked Atg5 alleles; results are presented relative to those of unstimulated Atg5f/fCD19-Cre B cells.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(d) Quantitative RT-PCR analysis of Atg5 mRNA in differentiating Atg5f/f and Atg5f/fCD19-Cre B cells at 0 and 3 d after stimulation with LPS, presented relative to that in untreated Atg5f/fCD19-Cre B cells. *P 0.05, **P 0.01 and ***P 0.001 (Student's t-test).",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(a) ELISA of anti-pneumovax IgM titers in diluted serum 1 day before and 4, 10 and 14 d after intraperitoneal immunization of Atg5f/f and Atg5f/fCD19-Cre mice with 1 μg pneumovax.",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "(b) Quantitative RT-PCR analysis of mRNA encoding IRF4 and Blimp-1 in CD138hiB220lo bone marrow PCs and B220hiCD138lo spleen B lymphocytes (control) sorted from Atg5f/f and Atg5f/fCD19-Cre mice, to confirm PC phenotype; results are presented relative to that of histone H3 mRNA (loading control). (c) Quantitative PCR analysis of genomic DNA assessing undeleted and deleted loxP-flanked Atg5 alleles in sorted B cells and PCs (as in b; presented as in Fig. 5c).",
    "ncbi_link": "Cre: 
histone H3: 
Atg5: 11793
CD19: 12478
IRF4: 16364
Blimp-1: 12142"
  },
  {
    "caption": "(d) Immunofluorescence of endogenous LC3 (left, top row) and immunoglobulin content (left, bottom row) in bone marrow PCs sorted from Atg5f/f and Atg5f/fCD19-Cre mice, and quantitative RT-PCR analysis of Atg5 mRNA in bone marrow PCs and spleen B cell populations (right) sorted from Atg5f/f and Atg5f/f CD19-Cre mice. Nuclei (left) are stained blue with Hoechst. Scale bar (left), 5 μm. *P 0.05, **P 0.01 and ***P 0.001 (Student's t-test).",
    "ncbi_link": "Cre: 
Atg5: 11793
CD19: 12478"
  },
  {
    "caption": "Flow cytometry analysis of Rex1-GFPd2 cells following addition of 10mM 2-DG during the 48h EpiLC induction. Representative GFP intensity distributions are depicted. Average proportions of Rex1-GFPd2 positive (GFP+) cells are quantified from two independent biological replicates.",
    "ncbi_link": "GFPd2: 
Rex1: 66932"
  },
  {
    "caption": "Expression analysis by qRT-PCR of naïve pluripotency and epiblast marker genes in bulk 48h cells after 10mM 2-DG treatment. Relative expression levels, normalized to control culture conditions, are shown. Graphs represent averages from triplicate (duplicate for Klf4 and Tfcp2l1) independent biological experiments.",
    "ncbi_link": "Klf4: 16600
Tfcp2l1: 81879"
  },
  {
    "caption": "Representative flow cytometry profiles of Rex1-GFPd2 cells following 4mM dm-αKG supplementation during the EpiLC induction are depicted. Graphs show average fractions of Rex1-GFPd2 positive (GFP+) cells from six independent biological assays.",
    "ncbi_link": "GFPd2: 
Rex1: 66932"
  },
  {
    "caption": "10-day culture of Rex1-GFPd2 cells in N2B27/Lif/KSR with 4mM dm-αKG and DMSO, respectively, with passaging every 2.5-days. (F) Characteristic bright field images of Rex1-GFPd2 cells after 10 days of culture in 2i/Lif/KSR and N2B27/Lif/KSR, in the presence of dm-αKG and DMSO, respectively. Scale bar, 10um.",
    "ncbi_link": "GFPd2: 
Rex1: 66932"
  },
  {
    "caption": "10-day culture of Rex1-GFPd2 cells in N2B27/Lif/KSR with 4mM dm-αKG and DMSO, respectively, with passaging every 2.5-days. Flow cytometer-based quantification of Rex1-GFPd2 positive (GFP+) cells. Representative GFP intensity distributions are displayed. The average fractions of GFP+ cells are measured from duplicate experiments.",
    "ncbi_link": "GFPd2: 
Rex1: 66932"
  },
  {
    "caption": "10-day culture of Rex1-GFPd2 cells in N2B27/Lif/KSR with 4mM dm-αKG and DMSO, respectively, with passaging every 2.5-days. qRT-PCR analysis of naïve pluripotency and differentiation markers in bulk cells harvested at 2.5 day-intervals during the 10-day culture in N2B27/Lif/KSR with dm-αKG or DMSO. Expression data are normalized to time-matched ESCs in 2i/Lif/KSR-culture conditions and are averaged over two independent biological experiments.",
    "ncbi_link": "GFPd2: 
Rex1: 66932"
  },
  {
    "caption": "FACS analysis of Prdm1-GFP positive (GFP+) cells in day-4 embryoids specified in the presence of 4mM dm-αKG and PGC cytokines. Representative flow cytometer profiles are depicted. Graphs show the average fractions of GFP+ cells from duplicate experiments. P1-GFP, Prdm1-GFP.",
    "ncbi_link": "GFP: 
Prdm1: 12142
P1: 12142"
  },
  {
    "caption": "FACS analysis of Prdm1-GFP positive (GFP+) cells in day-2 embryoids aggregated under addition of LIF (10ng ml-1) and BMP4 (500ng ml-1), dm-αKG (4mM), or DMSO. Representative flow cytometer profiles are displayed. Average fractions of GFP+ cells are calculated from duplicate assays. P1-GFP, Prdm1-GFP.",
    "ncbi_link": "GFP: 
Prdm1: 12142
P1: 12142"
  },
  {
    "caption": "FACS analysis of Prdm1-GFP positive (GFP+) cells in day-4 PGCLC aggregates specified from 4mM dm-αKG-treated (t=48h to t=72h) EpiLCs. Representative flow cytometer profiles are depicted. The average fractions of GFP+ cells, quantified from triplicate experiments, are shown. P1-GFP, Prdm1-GFP.",
    "ncbi_link": "GFP: 
Prdm1: 12142
P1: 12142"
  },
  {
    "caption": "Transcript analysis by qRT-PCR of PGC specifiers, demethylating enzymes, mesoderm, endoderm, and ESC regulators in FACS-sorted day-4 Prdm1-GFP embryoids induced from 4mM dm-αKG-treated 72h EpiLCs. Expression levels are normalized to Prdm1-GFP negative cells from control embryoids. Graphs represent averages from triplicate experiments. +, Prdm1-GFP positive cells; -, Prdm1-GFP negative cells.",
    "ncbi_link": "GFP: 
Prdm1: 12142"
  },
  {
    "caption": "ChIP-qPCR analysis of H3K9me2 and H3K27me3 in putative enhancer regions of genes associated with the naïve pluripotent state (Esrrb, Arid5b) and PGC fate (Tfap2c), respectively, in naïve ESCs and at t=48h following EpiLC induction in the presence of 4mM dm-αKG and DMSO, respectively. Graphs show enrichment of H3K9me2, H3K27me3, and IgG control, respectively, relative to DMSO-treated EpiLCs.",
    "ncbi_link": "Arid5b: 71371
Esrrb: 26380
Tfap2c: 21420"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cell viability was assessed by CellTiter-Glo (A) after 16 hours. Data are means ± SEM of three independent experiments. *P< 0.1, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cell viability was assessed by Crystal Violet (B) after 16 hours. Data are means ± SEM of three independent experiments. *P< 0.1, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Flow cytometric analysis of cells stained with TO-PRO-3 nd Annexin V (A5). Histograms show means ± SEM of three independent experiments. ***P<0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Flow cytometric analysis of cells stained with Annexin V (A5). Histograms show means ± SEM of three independent experiments. ***P<0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Flow cytometric analysis of cells stained with TO-PRO-3 Histograms show means ± SEM of three independent experiments. ***P<0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cells were collected after 4 and 24 hours of treatment, and stained with TO-PRO-3 Data are means ± SEM of three independent experiments. **P<0.01, ***P< 0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cells were collected after 4 and 24 hours of treatment, and stained with TO-PRO-3 Data are means ± SEM of three independent experiments. **P<0.01, ***P< 0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cells were collected after 4 hours of treatment, and stained with propidium iodide (PI) and A5 Data are means ± SEM of three independent experiments. **P<0.01, ***P< 0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). Cells were collected after 4 and 24 hours of treatment, and stained with propidium iodide (PI) Data are means ± SEM of three independent experiments. **P<0.01, ***P< 0.001, ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). J Measurement of lactate deshydrogenase (LDH) released from necroptotic cells, as indicated (means ± SEM, n=4 biological replicates, ****P<0.0001, ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with siRNA for MLKL or scramble non-specific (NS) siRNA for 72 hours. Cells pre-treated with 10 μM QVD-OPh (Q), 5 μM Birinapant (S), 20 μM necrostatin-1 (Nec-1s) were stimulated with 1-10 ng.mL-1 TNFα (T). K Time lapsed microscopy analysis of A5 and TO-PRO-3 staining upon induction of necroptosis. The presented data are representative of at least three independent experiments.",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "A HT-29 cells were transfected with two individual siRNA for PANX1, or scramble non-specific (NS) siRNA for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) together with 5 μM Birinapant (S), prior stimulation with 10 ng.mL-1 of TNFα (T), as indicated. Western blotting for hallmarks of necroptosis, as indicated. The arrowhead indicates MLKL cleaved fragment. Molecular weight markers (Mr) are shown.",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "HT-29 cells were infected with lentiviruses containing two individual sgRNA to deplete endogenous PANX1. A control nonspecific sequence (NC) was also used. Cells were treated with the addition of 1 μM cycloheximide (C) to enhance cell death, and analyzed by Western blotting (G).",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "HT-29 cells were infected with lentiviruses containing two individual sgRNA to deplete endogenous PANX1. A control nonspecific sequence (NC) was also used. Cells were treated with the addition of 1 μM cycloheximide (C) to enhance cell death Cell survival was assessed by CellTiter-Glo after 24 hours of treatment (H). Histogram shows means ± SEM, n=4 biological replicates, ****P<0.0001, ANOVA.",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "HT-29 cells were infected with lentiviruses containing two individual sgRNA to deplete endogenous PANX1. A control nonspecific sequence (NC) was also used. Cells were treated as in (A) with the addition of 1 μM cycloheximide (C) to enhance cell death Annexin V staining was analyzed by flow cytometry after 4 hours of stimulation Shown are means ± SEM, n=3 biological replicates, *P<0.1, ****P<0.0001, ANOVA.",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "HT-29 cells were infected with lentiviruses containing two individual sgRNA to deplete endogenous PANX1. A control nonspecific sequence (NC) was also used. Cells were treated with the addition of 1 μM cycloheximide (C) to enhance cell death TO-PRO-3 uptake was analyzed by flow cytometry after 4 hours of stimulation Shown are means ± SEM, n=3 biological replicates, *P<0.1, ****P<0.0001, ANOVA.",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "PANX1 expression was restored in PANX1 knockout cells after an infection with a lentivirus containing a PANX1 cDNA and expressing GFP. Cell lysates were analyzed by Western blotting as indicated (K).",
    "ncbi_link": "GFP: 
PANX1: 24145"
  },
  {
    "caption": "PANX1 expression was restored in PANX1 knockout cells after an infection with a lentivirus containing a PANX1 cDNA and expressing GFP. TO-PRO-3 uptake was analyzed by flow cytometry Shown are means ± SEM, n=3 biological replicates, ****P<0.0001 ANOVA.",
    "ncbi_link": "GFP: 
PANX1: 24145"
  },
  {
    "caption": "PANX1 expression was restored in PANX1 knockout cells after an infection with a lentivirus containing a PANX1 cDNA and expressing GFP. TO-PRO-3 uptake was analyzed by flow cytometry Shown are means ± SEM, n=3 biological replicates, ****P<0.0001 ANOVA.",
    "ncbi_link": "GFP: 
PANX1: 24145"
  },
  {
    "caption": "NS- and MLKL-silenced cells were pretreated with 100 μM carbenoxolone (CBX), 2 mM Probenecid (Probe) or 30 μM Trovafloxacin (Trova) and stimulated Cell survival was evaluated by CellTiter-Glo after 24 hours (N). Data are means ± SEM, n=4 biological replicates, ***P<0.001, ****P<0.0001, ANOVA.",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "NS- and MLKL-silenced cells were pretreated with 100 μM carbenoxolone (CBX), 2 mM Probenecid (Probe) or 30 μM Trovafloxacin (Trova) and stimulated TO-PRO-3 uptake was analyzed by flow cytometry (O). Data are means ± SEM, n=3 biological replicates, ***P<0.001, ****P<0.0001, ANOVA.",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with a nonspecific (NS) siRNA or with the indicated siRNAs for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) plus 5 μM Birinapant (S), and exposed to 10 ng.mL-1 of TNFα (T). NS- and MLKL-silenced cells were treated with 5 μM necrosulfonamide (NSA). MLKL oligomers (MLKLn) were visualized by non-reducing SDS-PAGE after cross-linking proteins (A). Data are means ± SEM of three independent experiments. ****P<0.0001 (ANOVA). Data information Arrowhead, MLKL cleaved fragment.",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with a nonspecific (NS) siRNA or with the indicated siRNAs for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) plus 5 μM Birinapant (S), and exposed to 10 ng.mL-1 of TNFα (T). NS- and MLKL-silenced cells were treated with 5 μM necrosulfonamide (NSA). MLKL oligomers (MLKLn) Cells were exposed to TQS for 5 hours. Molecular weight markers (Mr) are shown. TO-PRO-3 uptake was analyzed by flow cytometry in cells treated with TQS for 4 hours (B). Data are means ± SEM of three independent experiments. ****P<0.0001 (ANOVA).",
    "ncbi_link": "MLKL: 197259"
  },
  {
    "caption": "HT-29 cells were transfected with a nonspecific (NS) siRNA or with the indicated siRNAs for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) plus 5 μM Birinapant (S), and exposed to 10 ng.mL-1 of TNFα (T). C Cell lysates from NS-, and ITPK1-silenced cells were analyzed by Western blotting as indicated. Data information: Arrowhead, MLKL cleaved fragment.",
    "ncbi_link": "ITPK1: 3705"
  },
  {
    "caption": "A HT-29 cells were transfected with a siRNA for PANX1 (#3), or scramble non-specific (NS) siRNA for 72 hours. Cells were pre-treated with 10 μM QVD-OPh (Q) plus 5 μM Birinapant (S), and exposed to 10 ng.mL-1 of TNFα (T) for 6 hours. Shown is a normalized densitometric analysis for the presence of 120 cytokines with an antibody array. The color scale (0-10) represents the means of normalized densitometry values (n=2 technical replicates).",
    "ncbi_link": "PANX1: 24145"
  },
  {
    "caption": "B, C HT-29 transfected as indicated (B) or PANX1 knockout HT-29 cells (C) were treated with TQS for 6 hours. The mRNA levels of Cxcl8 relative to untreated NS or NC samples were measured by qPCR (means ± SEM, n=3 biological replicates, ****P<0.0001, ANOVA).",
    "ncbi_link": "Cxcl8: 3576
PANX1: 24145"
  },
  {
    "caption": "HT-29 cells were treated as indicated. Cxcl8 mRNA levels relative to untreated NS samples were measured by qPCR after 6 hours of treatment (F). Data are means ± SEM of three (F) independent experiments (***P<0.001, ****P<0.0001, ANOVA).",
    "ncbi_link": "Cxcl8: 3576"
  },
  {
    "caption": "HT-29 cells were treated as indicated. Cxcl8 mRNA levels relative to untreated NS samples were measured by qPCR after 6 hours of treatment (I). Data are means ± SEM of three (I) independent experiments (**P<0.01, ****P<0.0001, ANOVA).",
    "ncbi_link": "Cxcl8: 3576"
  },
  {
    "caption": "Induction of interferon-stimulated genes upon prestimulation with 1400 pM IFNα (yellow background) and stimulation with 1400 pM IFNα (white background) in Huh7.5 cells, assessed by qRT-PCR. RNA levels were normalized to the geometric mean of reference genes GAPDH, HPRT and TBP and were displayed as fold change. Peak of gene expression is indicated. Data points displayed as dots with 1σ confidence-interval estimated from biological replicates (N=4 to N=14) using a combined scaling and error model. Dashed lines indicate smoothing splines.   Induction of interferon-stimulated genes upon prestimulation with 2.8 pM IFNα (yellow background) and stimulation with 1400 pM IFNα (white background) in Huh7.5 cells, assessed by qRT-PCR. RNA levels were normalized to the geometric mean of reference genes GAPDH, HPRT and TBP and were displayed as fold change. Peak of gene expression is indicated. Data points are displayed as dots with 1σ confidence interval estimated from biological replicates (N=4 to N=6) using a combined scaling and error model. Dashed lines indicate smoothing splines.   ",
    "ncbi_link": "GAPDH: 
HPRT: 
TBP: "
  },
  {
    "caption": "Model calibration with time-resolved IFNα-induced feedback transcripts upon prestimulation with 0, 2.8 pM, 28 pM or 1400 pM IFNα, assessed by qRT-PCR. mRNA levels were normalized to the geometric mean of reference genes GAPDH, HPRT and TBP. Experimental data is represented by filled circles with errors representing 1σ confidence-interval estimated from biological replicates (N=3 to N=14) using a combined scaling and error model. Model trajectories are represented by lines.",
    "ncbi_link": "GAPDH: 
HPRT: 
TBP: "
  },
  {
    "caption": "Model predictions of IFNα-induced dynamics of occupied GAS bindings sites (OccGASbs) (left panel), of the sum of the pSTAT1:pSTAT2 heterodimers and the pSTAT1:pSTAT2:IRF9 trimers (middle panel) and of the pSTAT1:pSTAT2:IRF9 trimers (right panel) in untreated Huh7.5 cells and in Huh7.5 cells prestimulated for 24 hours with 280 pM IFNα that were subsequently stimulated with 1400 pM IFNα. Lines with shading represent model predictions with 68% confidence intervals using the prediction profile likelihood method. For experimental validation of the dynamics of OccGASbs, electrophoretic mobility shift assays (EMSA) were performed using nuclear protein lysates obtained from untreated Huh7.5 cells or Huh7.5 cells that were prestimulated for 24 hours with 280 pM IFNα and then stimulated with 1400 pM IFNα. Lysates were incubated with radioactively-labeled oligonucleotides probes harboring the GAS-binding region of the human IRF1 promoter. Samples were resolved on a native polyacrylamide gel and radioactivity was visualized and quantified from three independent experiments (left panel). For experimental validation of the dynamics of the sum of the pSTAT1:pSTAT2 heterodimers and the pSTAT1:pSTAT2:IRF9 trimers, immunoprecipitations (IP) were performed using total cell lysates obtained from untreated Huh7.5 cells or Huh7.5 cells that were prestimulated for 24 hours with 280 pM IFNα and then stimulated with 1400 pM IFNα. Lysates were subjected to immunoprecipitation with antibodies recognizing STAT2 and phosphorylated STAT1 was detected with quantitative immunoblotting (IB) (middle panel). For experimental validation of the dynamics of the pSTAT1:pSTAT2:IRF9 trimers, immunoprecipitations were performed using total cell lysates obtained from untreated Huh7.5 cells or Huh7.5 cells that were prestimulated for 24 hours with 280 pM IFNα and then stimulated with 1400 pM IFNα. Lysates were subjected to immunoprecipitation (IP) with antibodies recognizing IRF9 and phosphorylated STAT1 was detected with quantitative immunoblotting (IB) (right panel). Antibodies and the corresponding proteins in the complexes are underlined. Experimental data is represented by filled circles with errors representing 1σ confidence-interval estimated from biological replicates (N=3) using a combined scaling and error model.",
    "ncbi_link": "GAS: 
IRF1: 3659"
  },
  {
    "caption": "Model predictions of IFNα-induced dynamics of occupied GAS bindings sites (OccGASbs) and of occupied ISRE binding sites (OccISREbs) in Huh7.5 cells without prestimulation and in cells prestimulated for 24 hours with 28 pM and 280 pM IFNα that were subsequently stimulated with 1400 pM IFNα. Model predictions were performed using the prediction profile likelihood method. Lines with shading represent model predictions with 68% confidence intervals. For experimental validation, growth factor-depleted Huh7.5 cells were prestimulated with 0 pM, 28 pM and 280 pM IFNα. After 24 hours cells were stimulated with 1400 pM IFNα and IFNα-induced expression of target genes was measured by qRT-PCR. RNA levels were normalized to the geometric mean of reference genes GAPDH, HPRT and TBP, averaged and displayed as fold change, represented by filled circles with errors representing standard error of the mean calculated from biological replicates (N=3). Except for gene-specific parameters (mRNA synthesis and degradation rates, time-delay parameter and Hill coefficient), qRT-PCR data were used for model validation but not for model calibration.",
    "ncbi_link": "GAPDH: 
GAS: 
HPRT: 
ISRE: 
TBP: "
  },
  {
    "caption": "Knockdown of USP18 results in sustained signaling. USP18 knockdown efficiency determined by quantitative immunoblotting of cytoplasmic lysates of Huh7.5 transfected with USP18 siRNA relative to parental Huh7.5 cells and Huh7.5 cells transfected with non-targeting siRNA. Cells were stimulated with 1400 pM IFNα for 24 hours. Error bars represent 1σ confidence intervals estimated from biological replicates (N=6 to N=10) (left). Model fit and experimental data of Huh7.5 cells transfected with control siRNA or USP18 siRNA are shown. Cells were transfected with USP18 siRNA or control siRNA 1 day prior to growth factor-depletion. Next, cells were prestimulated with 1400 pM IFNα (yellow background) and stimulated with 1400 pM IFNα at 24 hours or untreated (white background). IFNα-induced phosphorylation of STAT1 and STAT2 and induction of USP18 and tSTAT1, comprising both phosphorylated and unphosphorylated STAT1 protein, are displayed. Experimental data were obtained by quantitative immunoblotting using chemiluminescence and CCD camera device (ImageQuant). For model purposes data in control siRNA and untransfected Huh7.5 are combined to one condition. Data from multiple time courses scaled together is displayed as filled circles with errors representing 1σ confidence interval estimated from biological replicates (N=2 to N=10) using a combined scaling and error model. Lines represent model trajectories.",
    "ncbi_link": "USP18: 11274"
  },
  {
    "caption": "Overexpression of Huh7.5 is not sufficient to explain negative memory. Induced expression of USP18 after treatment of Huh7.5-TetON-USP18 and Huh7.5-TetON-control cells with doxycycline for 24 hours in comparison with parental Huh7.5 cells treated with 1400 pM IFNα for 24 hours. Analysis was performed by quantitative immunoblotting. Error bars represent 1σ confidence intervals estimated from biological replicates (N=3 to N=5) (left). Model fits and experimental data of Huh7.5-TetON-USP18 treated with doxycycline for 24 hours and stimulated with 1400 pM IFNα or parental Huh7.5 cells prestimulated with 0 or 1400 pM IFNα and stimulated with 1400 pM IFNα after 24 hours are shown. The dynamics of IFNα-induced phosphorylation of STAT1 and STAT2 and induction of USP18 are depicted. Experimental data was obtained by quantitative immunoblotting using chemiluminescence and CCD camera device (ImageQuant). For modeling purposes data from Huh7.5-TetON empty vector control and untransduced Huh7.5 are combined to one condition. Data is displayed as filled circles with errors representing 1σ confidence-interval estimated from biological replicates (N=3 to N=4) using a combined scaling and error model. Line represents model trajectories.",
    "ncbi_link": "USP18: 11274"
  },
  {
    "caption": "(C) ELISA of IL-1β in the supernatants of wild type (WT), NLRP3 knockout (KO) #1 or AIM2 KO#1 THP-1 cells left untreated (UT), or pretreated with LPS (500 ng/ml, 3 hrs) followed by ATP (5 mM, 6 hrs) stimulation, or stimulated with poly (dA:dT) (1mg/ml, 6 hrs), or infected with ZIKV (MOI=1, 36 hrs).",
    "ncbi_link": "AIM2: 9447
NLRP3: 114548"
  },
  {
    "caption": "(D) ELISA of IL-1β in the supernatants of two clones of NLRP3 KO THP-1 cells with or without ZIKV infection (MOI=1) at the indicated time points.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(E) ELISA of IL-1β in the supernatants of PBMCs from two donors transfected with control (ctrl) siRNA or NLRP3 siRNA followed by ZIKV infection (MOI=1) for 36 hrs.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(F) ELISA of IL-1β in the supernatant of WT, NLRP3 KO or AIM2 KO THP-1 cells with ZIKV (MR766 or GZ01) (MOI=1) or DENV-2 (MOI=1) infection for 36 hrs.",
    "ncbi_link": "AIM2: 9447
NLRP3: 114548"
  },
  {
    "caption": "(I) Immunoblot analysis of supernatants and cell extracts of 293T cells transfected with plasmids expressing NLRP3, ASC, pro-caspase-1 and pro-IL-1β together with NS1.",
    "ncbi_link": "NS1: 
caspase-1: 834
IL-1β: 3553
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "(J) Immunoblot analysis of protein extracts of Flag-tagged NS1-inducible THP-1 cells treated with increasing doses of doxycycline (Dox) for 24 hrs.",
    "ncbi_link": "Flag: 
NS1: "
  },
  {
    "caption": "(K) ELISA of IL-1β in the supernatants of Flag-NS1-inducible THP-1 cells left unprimed then treated with ATP (5 mM, 6 hrs) or poly (I:C) (2 mg/ml, 6 hrs), or pre-treated with LPS (500 ng/ml, 3 hrs) followed by ATP (5 mM, 6 hrs) or poly (I:C) (2 mg/ml, 6 hrs) stimulation.",
    "ncbi_link": "Flag: 
NS1: "
  },
  {
    "caption": "(L) Immunoblot analysis of supernatants (Sup) and cell extracts (Lys) of Flag-NS1-inducible THP-1 cells pre-treated with LPS (500 ng/ml, 3 hrs) followed by ATP (5 mM, 6 hrs) or poly (I:C) (2 mg/ml, 6 hrs) stimulation.",
    "ncbi_link": "Flag: 
NS1: "
  },
  {
    "caption": "(B) Relative qRT-PCR analysis of ZIKV RNA in wild type (WT) or NLRP3 knockout (KO) THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(C) Immunoblot analysis of extracts of WT or Nlrp3-/- BMDMs by the indicated antibodies.",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(D) Relative qRT-PCR analysis of ZIKV RNA in WT or Nlrp3-/- BMDMs infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(E) Plaque titration of ZIKV in supernatants of WT or Nlrp3-/- BMDMs infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(F) Immunoblot analysis of extracts of WT or caspase-1 KO THP-1 cells by the indicated antibodies.",
    "ncbi_link": "caspase-1: 834"
  },
  {
    "caption": "(G) Relative qRT-PCR analysis of ZIKV RNA in WT or caspase-1 KO THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "caspase-1: 834"
  },
  {
    "caption": "(H) Relative qRT-PCR analysis of ZIKV RNA in NS-1-inducible THP-1 cells treated with or without doxycycline (Dox), then left untreated or treated with Ac-YVAD-cmk (20 μΜ) for 3 hrs followed by ZIKV infection (MOI=1) for the indicated time points.",
    "ncbi_link": "NS-1: "
  },
  {
    "caption": "(I) Relative qRT-PCR analysis of NLRP3 knockdown efficiency in PBMCs from two donors.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(J) Relative qRT-PCR analysis of ZIKV RNA in PBMCs transfected with control siRNA or NLRP3 siRNA then infected with ZIKV (MOI=1) for 36 hrs.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(A) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with HA-NS1 together with Flag-NLRP3, Flag-ASC, Flag-caspase-1 and Flag-IL-1β. WCL, whole cell lysates.",
    "ncbi_link": "Flag: 
HA: 
NS1: 
caspase-1: 834
IL-1β: 3553
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "(B) Co-immunoprecipitation and immunoblot analysis of extracts of NS1-inducible THP-1 cells, which expressed Flag-tagged NS1, treated with or without doxycycline (Dox) (100 ng/ml).",
    "ncbi_link": "NS1: "
  },
  {
    "caption": "(D) Immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 together with increasing amount of HA-NS1. Below, caspase-1 mRNA RT-PCR; RPL13A mRNA RT-PCR serves as a loading control.",
    "ncbi_link": "RPL13A: 
Flag: 
HA: 
NS1: 
caspase-1: 834"
  },
  {
    "caption": "(E) Immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 together with increasing amount of HA-DENV-2-NS1.",
    "ncbi_link": "Flag: 
HA: 
NS1: 
caspase-1: 834"
  },
  {
    "caption": "(F) Immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 together with empty vector or HA-NS1 followed by cycloheximide (CHX) treatment (100 μg/ml) for the indicated time points.",
    "ncbi_link": "Flag: 
HA: 
NS1: 
caspase-1: 834"
  },
  {
    "caption": "(G) Immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 together with empty vector or HA-NS1 then treated with MG132 (10 mM), Lactacystin (5 μM), Carfilzomib (100 mM) or CQ (50 mM) for 6 hrs.",
    "ncbi_link": "Flag: 
HA: 
NS1: 
caspase-1: 834"
  },
  {
    "caption": "(H) Co-immunoprecipitation and immunoblot analysis of extracts of Flag-NS1-inducible THP-1 cells treated with or without Dox (100 ng/ml).",
    "ncbi_link": "Flag: 
NS1: "
  },
  {
    "caption": "(I) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with plasmids expressing Flag-caspase-1 and indicated HA-tagged WT ubiquitin or mutants (K6-, K11-, K27-, K29-, K33-, K48- and K63-Only), together with empty vector or Myc-NS1, followed by MG132 (10 mM) treatment for 6 hrs.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
NS1: 
ubiquitin: 
caspase-1: 834"
  },
  {
    "caption": "(A) Immunoblot analysis of extracts of wild type (WT) and USP8 knockout (KO) 293T cells transfected with Flag-caspase-1 together with empty vector or Myc-NS1.",
    "ncbi_link": "Flag: 
Myc: 
NS1: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(B) Immunoblot analysis of extracts of transfected with Flag-caspase-1 together with empty vector or Myc-USP8 then treated with or without MG132 (10 mM) for 6 hrs.",
    "ncbi_link": "Flag: 
Myc: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(C) Co-immunoprecipitation and immunoblot analysis of extracts of Flag-NS1-inducible THP-1 cells treated with or without Dox (100 ng/ml) then transfected with or without poly (I:C) (2 mg/ml, 6 hrs).",
    "ncbi_link": "Flag: 
NS1: "
  },
  {
    "caption": "(D) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 and Myc-USP8 together with HA-NS1 followed by MG132 treatment (10 mM) for 6 hrs.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
NS1: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(F) Co-immunoprecipitation and immunoblot analysis of extracts of WT and USP8 KO THP-1 cells infected with ZIKV (MOI=1) for 24 hrs.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "(G) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with plasmids expressing Flag-caspase-1 and indicated HA-tagged WT ubiquitin (Ub) or mutants (K6-, K11-, K27-, K29-, K33-, K48- and K63-Only), together with empty vector or Myc-USP8, followed by MG132 (10 mM) treatment for 6 hrs.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
ubiquitin: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(H) Immunoblot analysis of extracts of WT or USP8 KO 293T cells transfected with Flag-caspase-1, HA-K11-Ub together with empty vector or Myc-NS1, followed by two-step immunoprecipitation with anti-Flag beads and immunoblot analysis with anti-HA.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
NS1: 
Ub: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(I) Co-immunoprecipitation and immunoblot analysis of extracts of USP8 KO 293T cells transfected with Flag-caspase-1 and HA-K11-Ub together with WT or inactive mutant C786A of USP8.",
    "ncbi_link": "Flag: 
HA: 
Ub: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(A) Immunoblot analysis of extracts of 293T cells transfected with empty vector or HA-NS1 together with Flag-caspae-1 wild type (WT) and mutants (K37R, K44R or K134R). Lower panel shows the intensity analysis of the bands from the three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
NS1: 
caspae-1: 834"
  },
  {
    "caption": "(B) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with HA-K11-ubiquitin (Ub) together with Flag-caspase-1 (WT, K37R, K44R, K134R).",
    "ncbi_link": "Flag: 
HA: 
Ub: 
ubiquitin: 
caspase-1: 834"
  },
  {
    "caption": "(C) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 (WT or K134R) and HA-K11-Ub, together with empty vector or Myc-NS1. Lower panel shows the intensity analysis of the bands from the three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
NS1: 
Ub: 
caspase-1: 834"
  },
  {
    "caption": "(D) Co-immunoprecipitation and immunoblot analysis of extracts of 293T cells transfected with Flag-caspase-1 (WT or K134R) and HA-K11-Ub, together with empty vector or Myc-USP8. Lower panel shows the intensity analysis of the bands from the three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
caspase-1: 834
USP8: 9101"
  },
  {
    "caption": "(A) Relative qRT-PCR analysis of IFNB, IFIT2 and IFIT1 mRNA levels in wild type (WT) or caspase-1 knockout (KO) THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "caspase-1: 834
IFIT1: 3434
IFIT2: 3433
IFNB: 3456"
  },
  {
    "caption": "(B) Relative qRT-PCR analysis of IFNB mRNA levels in THP-1 cells left untreated or treated with LPS (500 ng/ml, 3 hrs) and ATP (5 mM, 6 hrs), followed by ZIKV infection (MOI=1) for the indicated time points.",
    "ncbi_link": "IFNB: 3456"
  },
  {
    "caption": "(C) Relative qRT-PCR analysis of IFNB mRNA levels in wild type (WT) or NLRP3 knockout (KO) THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "IFNB: 3456
NLRP3: 114548"
  },
  {
    "caption": "(D) Relative qRT-PCR analysis of IFNB , IFIT2 and IFIT1 mRNA levels in Flag-NS1-inducible THP-1 cells treated with or without Dox then left untreated or treated with YVAD (20 μM) for 3 hrs, followed by ZIKV infection (MOI=1) for the indicated time points.",
    "ncbi_link": "Flag: 
NS1: 
IFIT1: 3434
IFIT2: 3433
IFNB: 3456"
  },
  {
    "caption": "(E) Relative qRT-PCR analysis of IFNB mRNA in PBMCs transfected with control siRNA or NLRP3 siRNA then infected with ZIKV (MOI=1) for 36 hrs.",
    "ncbi_link": "IFNB: 3456
NLRP3: 114548"
  },
  {
    "caption": "(F) Relative qRT-PCR analysis of IFNB mRNA in PBMCs treated with DMSO or Ac-YVAD-cmk (20μM) for 3hrs followed by ZIKV infection (MOI=1) for 36 hrs.",
    "ncbi_link": "IFNB: 3456"
  },
  {
    "caption": "(H) ELISA of IL-1β production in brain of WT or Nlrp3-/- 1-day-old neonatal mice (n=3 per group) intracerebrally injected with 1×105 plaque-forming units (PFU) of ZIKV for 5 days.",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(I) Relative qRT-PCR analysis of IFNB mRNA levels in brain tissues of WT or Nlrp3-/- neonatal mice with or without ZIKV infection",
    "ncbi_link": "IFNB: 15977
Nlrp3: 114548"
  },
  {
    "caption": "(J) ELISA of IFN-β production in brains of WT or Nlrp3-/- neonatal mice",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(K) Relative qRT-PCR analysis of ZIKV RNA levels in brain tissues of WT or Nlrp3-/- neonatal mice with or without ZIKV infection",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(L) Plaque titration of ZIKV in brain tissues of WT or Nlrp3-/- neonatal mice",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(M) Body weight gain of WT and Nlrp3-/- neonatal mice (n=4 per group) inoculated with ZIKV (1×105 PFUs).",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(A) Relative qRT-PCR analysis of ZIKV RNA levels in wild type (WT) or cGAS knockout (KO) THP-1 cells after ZIKV infection (MOI=1) for indicated time points.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "(B) Relative qRT-PCR analysis of IFNΒ, IFIT2 and IFIT1 mRNA levels in WT or cGAS KO THP-1 cells after ZIKV infection (MOI=1) for indicated time points.",
    "ncbi_link": "cGAS: 115004
IFIT1: 3434
IFIT2: 3433
IFNΒ: 3456"
  },
  {
    "caption": "(C) Relative qRT-PCR analysis of ZIKV RNA and IFNB mRNA levels in PBMCs transduced with Cas9 and small guide RNA targeting GFP, cGAS or NLRP3 and infected with ZIKV (MOI=1) for 36 hrs.",
    "ncbi_link": "Cas9: 
GFP: 
cGAS: 115004
IFNB: 3456
NLRP3: 114548"
  },
  {
    "caption": "(D) Relative qRT-PCR analysis of ZIKV RNA and IFNΒ mRNA levels in WT or cGAS KO THP-1 cells treated with or without YVAD (20 μM), followed by ZIKV infection (MOI=1) for indicated times points.",
    "ncbi_link": "cGAS: 115004
IFNΒ: 3456"
  },
  {
    "caption": "(E) Immunoblot analysis of extracts of Flag-cGAS-overexpressed THP-1 cells treated with or without YVAD (20 μM) then infected with ZIKV (MOI=5) for 24 hrs or infected with HSV-1 (MOI=1) for 24 hrs.",
    "ncbi_link": "Flag: 
cGAS: 214763"
  },
  {
    "caption": "Immunoblot analysis of WT, NLRP3 KO (F) THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "Immunoblot analysis of WT, caspase-1 KO (G) THP-1 cells infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "caspase-1: 834"
  },
  {
    "caption": "(H) Immunoblot analysis of extracts of WT or Nlrp3-/- BMDMs infected with ZIKV (MOI=1) for the indicated time points.",
    "ncbi_link": "Nlrp3: 114548"
  },
  {
    "caption": "(I) Immunoblot analysis of PBMCs from Donor#1 transfected with control siRNA or NLRP3 siRNA followed by ZIKV infection (MOI=1) for the indicated time points.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "(J) Immunoblot analysis of extracts of 293T cells transfected with Myc-cGAS (tagged on C-terminal), GFP-ASC, Flag-caspase-1, together with empty vector or HA-NS1.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
Myc: 
NS1: 
caspase-1: 834
cGAS: 214763
ASC: 29108"
  },
  {
    "caption": "(K) Relative qRT-PCR analysis of ZIKV RNA and IFNB mRNA levels in WT, cGAS KO THP-1 cells as well as cGAS KO THP-1 cells reconstituted with WT or D140A/D157A mutant of cGAS, followed by ZIKV infection (MOI=1) for 24 hrs.",
    "ncbi_link": "cGAS: 115004
IFNB: 3456"
  },
  {
    "caption": "B Heat map showing p53‐dependent regulation of \"EMT\"‐ and \"stemness\"‐related genes in KNCtumor cells. Fold change relative to control cells is displayed in a green red color scheme for selected genes with FClog2 1.0 or FClog2 > −1.0.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "C Statistical analysis of wound healing assay performed in primary KNCtumor cells following p53 depletion. Time‐lapse analyzer software was used to quantify the wound closure rate. Means ± SD are shown from one out of three independent experiments.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "D Western blot analysis revealing protein expression levels upon p53 depletion in KNCtumor cells.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "E X‐fold mRNA expression of EMT‐related marker genes after p53 depletion in KNCtumor cells. Means ± SD from at least three independent experiments are shown. Asterisks display significance (*P 0.05).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "A Kaplan-Meier curves showing survival of KNC, KPNC, and KPΔNC mice under the control of p48‐Cre pancreas‐specific promoters (P 0.0001 for KPNC or KPΔNC cohorts versus KNC, log‐rank test, for pairwise combination).",
    "ncbi_link": "Cre: 
p48: 16391"
  },
  {
    "caption": "B Relative mRNA expression of NFATc1‐ and EMT‐related marker genes on administration of CsA (1 μM) in KPNC cells. Data represents means ± SD from at least three independent experiments. Asterisks show significance (*P 0.05).",
    "ncbi_link": "NFATc1: 18018"
  },
  {
    "caption": "C Western blot analysis revealing protein expression levels in KPNC cells from the indicated proteins following transfection of siRNA control or siRNA toward NFATc1, respectively.",
    "ncbi_link": "NFATc1: 18018"
  },
  {
    "caption": "A Sox2 mRNA expression of pancreatic lysates from KNC, KPNC, and KPC mice, analyzed by real‐time PCR in three independent experiments (means ± SD).",
    "ncbi_link": "Sox2: 20674"
  },
  {
    "caption": "E, F NFATc1 and Sox2 protein expression after (E) NFATc1 depletion or (F) upon CsA (1 μM, 24 h) treatment in Panc1 cells.",
    "ncbi_link": "NFATc1: 4772"
  },
  {
    "caption": "G Sox2 and E‐cadherin mRNA expression after NFATc1 depletion in L3.6 cells.",
    "ncbi_link": "E‐cadherin: 999
NFATc1: 4772
Sox2: 6657"
  },
  {
    "caption": "I, J ChIP assays show NFATc1 binding to Sox2 enhancer and promoter in KNC tumor cells (I)",
    "ncbi_link": "Sox2: 20674"
  },
  {
    "caption": "I, J ChIP assays show RNA polymerase II binding to Sox2 promoter upon CsA (1 μM, 24 h) treatment in L3.6 cells (J).",
    "ncbi_link": "Sox2: 6657"
  },
  {
    "caption": "L ChIP experiments show NFATc1 binding along with H3K27 acetylation (H3K27ac) mark at the selected Snai1 enhancer region and RNA polymerase II binding at Snai1 promoter in the presence or absence of Sox2 in KPNC tumor cells. Representative results from at least three independent experiments are shown (means ± SD; P 0.05).",
    "ncbi_link": "Snai1: 20613
Sox2: 20674"
  },
  {
    "caption": "M Relative mRNA expression levels of EMT‐related marker genes upon Sox2 depletion in KPNC tumor cells (P 0.05).",
    "ncbi_link": "Sox2: 20674"
  },
  {
    "caption": "N Zeb1 and Snail mRNA levels in L3.6 cells after shRNA‐mediated depletion of Sox2 and transient overexpression of NFATc1 shows that loss of Sox2 significantly rescues NFATc1‐mediated induction of EMT genes (*P 0.05).",
    "ncbi_link": "NFATc1: 4772
Snail: 6615
Sox2: 6657
Zeb1: 6935"
  },
  {
    "caption": "B Relative mRNA expression of NFATc1 and Sox2 in L3.6 cells as well as in KPNCmicetumor cells (adherent versus spheres). Graph represents data from three independent experiments (means ± SD). Asterisks display significance (*P 0.05).",
    "ncbi_link": "NFATc1: 18018
Sox2: 20674"
  },
  {
    "caption": "C Cell sorting was performed to collect CD44 high and low populations in KPNC spheres (left panel), which were analyzed for NFATc1 and Sox2 mRNA expression (right panel).",
    "ncbi_link": "NFATc1: 18018
Sox2: 20674"
  },
  {
    "caption": "D Sox2 mRNA expression upon CsA (1 μM) treatment in L3.6 cells (adherent versus spheres) (*P 0.05).",
    "ncbi_link": "Sox2: 6657"
  },
  {
    "caption": "E Bright‐field light microscopy images as well as quantification of KPNC spheres after transient NFATc1 depletion.",
    "ncbi_link": "NFATc1: 18018"
  },
  {
    "caption": "A Expression analysis of indicated miRNAs upon adenoviral re‐expression of p53 in KPΔNC tumor cells, detected by real‐time PCR (P 0.05).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "B Protein expression of EMT marker genes after adenoviral re‐expression of GFP‐tagged p53 in KPΔNC tumor cells.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "C, D Protein (C) expression levels of EMT and stemness marker genes upon miRNA‐34a and miRNA‐200c overexpression using specific mimics in KPNC tumor cells. Representative results from at least three independent experiments are shown (means ± SD; P 0.05).",
    "ncbi_link": "miRNA‐200c: 723944
miRNA‐34a: 723848"
  },
  {
    "caption": "C, D mRNA (D) expression levels of EMT and stemness marker genes upon miRNA‐34a and miRNA‐200c overexpression using specific mimics in KPNC tumor cells. Representative results from at least three independent experiments are shown (means ± SD; P 0.05).",
    "ncbi_link": "miRNA‐200c: 723944
miRNA‐34a: 723848"
  },
  {
    "caption": "E Western blot analysis of EMT marker expression in KNC cells following depletion of miR‐200c.",
    "ncbi_link": "miR‐200c: 723944"
  },
  {
    "caption": "F ChIP experiments showing NFATc1 binding along with H3K27 acetylation mark at the selected Snai1 enhancer region as well as Sox2 and RNA polymerase II binding at Snai1 promoter after miR‐200c overexpression in KPNC tumor cells. Means ± SD are shown from one out of three independent experiments.",
    "ncbi_link": "miR‐200c: 723944
Snai1: 20613"
  },
  {
    "caption": "G ChIP analysis in KP∆NC tumor cells after adenoviral GFP‐tagged p53 overexpression. NFATc1 and H3K27ac binding are illustrated on Snai1 enhancer, and Sox2 and RNA polymerase II binding are demonstrated on Snai1 promoter. Means ± SD are shown from one out of three independent experiments.",
    "ncbi_link": "Snai1: 20613
p53: 22059"
  },
  {
    "caption": "H Quantification of KP∆NC tumour cell-derived spheres after adenoviralGFP‐tagged p53 overexpression.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "Flow cytometry detection of the Bhlhe40 (grey) and Bhlhe41 (orange) transcripts by the PrimeFlow RNA assay in alveolar (right) and peritoneal (left) macrophages. A probe specific for the Cd8a mRNA (black line) was used as a negative control. Results representative of at least four independent experiments.",
    "ncbi_link": "Cd8a: 
Bhlhe40: 20893
Bhlhe41: 79362"
  },
  {
    "caption": "Frequency of WT donor (CD45.1), DKO donor (CD45.2) and recipient (CD45.1/2) cells in the indicated BM (LSK, CMP), splenic (monocytes), liver (Kupffer cells), peritoneal and alveolar macrophage populations of lethally irradiated recipients ≥ 6 weeks after transfer of a 1:1 mixture of lineage-depleted BM cells from WT and DKO mice. P values < 0.05 (paired Student's t-test) between LSK and other populations are shown for frequencies of WT cells. Three mixed BM chimeras analyzed; error bars represent s.d. Representative results of three independent experiments.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "Frequency of WT donor (CD45.1), DKO donor (CD45.2) and recipient (CD45.1/2) cells among the BM LSK cells, splenic monocytes and alveolar macrophages of the recipients that were irradiated with lung shielding, treated with one dose of busulfan as described in Materials and Methods, transferred with a 1:1 mixture of lineage-depleted BM cells from WT and DKO mice and analyzed ≥ 8 weeks after transfer. Representative flow cytometry results for alveolar macrophages (left) and quantification (right) is shown.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "Surface phenotype of cells from the digested lungs (right) and quantification of donor contribution to the AM compartment (left) of AM-deficient Csf2rb-/-Csf2rb2-/-recipients (CD45.2) that were subjected to intranasal transfer of a 1:1 mixture of sorted fetal liver monocytes from WT (CD45.1/2) and DKO (CD45.2) E18.5 embryos at days 1 or 2 after birth and analyzed ≥ 7 weeks after the transfer. Cell surface phenotype of lung cells from a Csf2rb-/-Csf2rb2-/- mouse that was not subjected to the transfer is shown for comparison.",
    "ncbi_link": "Csf2rb: 12983
Csf2rb2: 12984
CD45: 19264"
  },
  {
    "caption": "WT (CD45.1) and DKO (CD45.2) AMs were sorted, mixed in a 1:1 ratio, labeled with CellTrace Violet and cultured in the presence of GM-CSF. The ratio of CD45.1 and CD45.2 cells and CellTrace Violet dilution was analyzed prior to culture (day 0) and after 7 days of culture as described in Materials and Methods.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "RNA-seq analysis of Maf and Mafb expression in WT and DKO AMs, which were isolated by flow cytometry from mice in steady state (top) or from mixed BM chimeras (bottom).",
    "ncbi_link": "Maf: 17132
Mafb: 16658"
  },
  {
    "caption": "RNA-seq analysis of Acaa1b and Hsd17b4 expression in WT and DKO AMs, which were isolated by flow cytometry from mice in steady state (top) or from mixed BM chimeras (bottom).",
    "ncbi_link": "Acaa1b: 235674
Hsd17b4: 15488"
  },
  {
    "caption": "Presence of RNA transcripts (RNA-seq; top) at the Gas7 and Acaa1b genes in WT and DKO AMs; the ChIP-seq analysis of H3K27 acetylation in WT and DKO AMs (middle) and Bhlhe40 binding in WT AMs (bottom). All analyses performed on ex vivo AMs.",
    "ncbi_link": "Acaa1b: 235674
Gas7: 14457"
  },
  {
    "caption": "Confirmation of the expression of SnRK1K139R-YFP or SnRK1-YFP fusion protein each in two transgenic lines, SnRK1K139R-YFP-L13 and -L22 or SnRK1-YFP-L4 and -L17, by immunoblotting. The protein samples analyzed here or in (B) and (C) were all prepared from BYDV-infected barley plants at 21 dpi.",
    "ncbi_link": "SnRK1: 
YFP: "
  },
  {
    "caption": "Phosphorylation of BYDV 17K was increased in SnRK1-YFP-L4 plants overexpressing SnRK1-YFP but reduced in SnRK1K139R-YFP-L13 ectopically expressing SnRK1K139R-YFP compared with WT control. P, phosphorylated 17K bands.",
    "ncbi_link": "SnRK1: 
YFP: "
  },
  {
    "caption": "Levels of GFP siRNA detected by sRNA blotting for the panel of tobacco materials shown in (A), with arrowhead indicating the main band of GFP siRNA.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Protein levels of PEBV CP and corrected expression of 17K, 17K5A or 17K5D in the panel of tobacco plants shown in (D), revealed using immunoblotting with anti-PEBV CP or anti-17K antibody.",
    "ncbi_link": "17K: 1493892"
  },
  {
    "caption": "17K5D, but not BYDV 17K, interacted with HvSDN1 in LC (B) assays. Expression of 17K and 17K5D in the LC assays were verified by immunoblotting using anti-17K antibody.",
    "ncbi_link": "17K: 1493892"
  },
  {
    "caption": "C 17K5D, but not 17K or 17K5A, showed binding to BYDV vsiRNA. The GST fusions of 17K, 17K5D, and 17K5A, as well as free GST, were used in the RNA EMSA assays with biotin-labeled vsiRNA899 or vsiRNA899 duplex as probes.",
    "ncbi_link": "vsiRNA899: "
  },
  {
    "caption": "Cleavage of BYDV vsiRNA899 by HvSDN1 (His-HvSDN1), with AtSDN1 (His-AtSDN1) serving as a positive control. Asterisk denotes cleavage products. The GST fusions of 17K and 17K5D did not show vsiRNA cleavage activity.",
    "ncbi_link": "vsiRNA899: "
  },
  {
    "caption": "Inhibition of HvSDN1-catalyzed vsiRNA cleavage by GST-17K5D but not GST-17K. Free GST protein served as a negative control. Asterisk denotes cleavage products.",
    "ncbi_link": "vsiRNA: "
  },
  {
    "caption": "The three mutants of 17K5D (17K5Dm4, 17K5Dm2a, and 17K5Dm2b) retained the ability to interact with HvSDN1 but their GST fusions failed to bind vsiRNA899 (D). Neither GST nor GST-17K showed vsiRNA899 binding.",
    "ncbi_link": "vsiRNA899: "
  },
  {
    "caption": "Quantitative analysis of HvSDN1 cleavage activities, with the fluorescence recorded using Typhoon FLA9500 (F and G) Compared with free GST or GST-17K, the GST fusions of 17K5D or three derivative mutants (17K5Dm4, 17K5Dm2a, and 17K5Dm2b) inhibited HvSDN1-catalzyed cleavage of fluorogenic vsiRNA899, which was revealed by a fluorospot assay (F), relative comparison of fluorescence values (G)",
    "ncbi_link": "vsiRNA899: "
  },
  {
    "caption": "Co-IP assays revealing the presence of vsiRNA-containing HvAGO1-HvSDN1-P17K complex in BYDV-infected WT, SnRK1K139R-YFP-L13, and SnRK1-YFP-L4 plants, with mock-inoculated SnRK1-YFP-L4 individuals as controls. The immunoprecipitates, prepared using anti-HvAGO1 antibody, were analyzed for the presence of HvSDN1 (by immunoblotting with anti-HvSDN1 antibody), P17K (asterisk) and 17K (arrowhead) (using Phos-tag SDS-PAGE coupled immunoblotting), and BYDV vsiRNA (by sRNA blotting). Compared with WT control, the HvAGO1 immunoprecipitates derived from SnRK1-YFP-L4 contained higher levels of P17K and vsiRNA but less amount of HvSDN1, whereas the reverse was observed for SnRK1K139R-YFP-L13.",
    "ncbi_link": "SnRK1: 
vsiRNA: 
YFP: "
  },
  {
    "caption": "Co-IP assays demonstrating that the interaction between HvAGO1 and HvSDN1 was weakened by P17K. The immunoprecipitates were prepared using anti-HvSDN1 antibody from the panel of plants shown in (B). Relative to WT control, the HvSDN1 immunoprecipitates derived from SnRK1-YFP-L4 contained much less HvAGO1, whereas the opposite was observed for SnRK1K139R-YFP-L13.",
    "ncbi_link": "SnRK1: 
YFP: "
  },
  {
    "caption": "17K5D compromised the interaction between HvSDN1 and the PAZ domain of HvAGO1. The LUC signal resulted from the interaction between HvSDN1-HvAGO1 PAZ domain was significantly decreased in the presence of 17K5D but not that of 17K.",
    "ncbi_link": "LUC: 
17K: 1493892"
  },
  {
    "caption": "Verification of 17K5D expression in the transgenic lines 17K5D-L3 and -L7 by immunoblotting with anti-17K antibody.",
    "ncbi_link": "17K: 1493892"
  },
  {
    "caption": "BYDV vsiRNA abundance in the set of samples shown in (B), as detected by sRNA blotting at 14 dpi.",
    "ncbi_link": "vsiRNA: "
  },
  {
    "caption": "Relative to TaSDN1-DD line, TaSDN1 protein was decreased in TaSDN1-Dd and TaSDN1-dd mutants, with a stronger reduction found for TaSDN1-dd. The reactive TaSDN1 protein detected in TaSDN1-dd was caused by the un-mutated TaSDN1-A and -B homoeologs.",
    "ncbi_link": "SDN1: "
  },
  {
    "caption": "protein (M) levels of BYDV CP gene in TaSDN1-DD, TaSDN1-Dd and TaSDN1-dd plants at 21 dpi. ",
    "ncbi_link": "SDN1: "
  },
  {
    "caption": "BYDV vsiRNA abundance in TaSDN1-DD, TaSDN1-Dd, and TaSDN1-dd plants detected by sRNA blotting at 21 dpi of BYDV.",
    "ncbi_link": "SDN1: 
vsiRNA: "
  },
  {
    "caption": "In vitro uptake is independent of components involved in homotypic vacuolar fusion. (A) Standard uptake reactions were performed (60 min, 27°C) in the presence of the indicated reagents using a mixture of vacuoles from strains DBY5734-16 (Δpep4) and DBY5734-19 (Δpho8). Therefore, homotypic vacuolar fusion and luciferase uptake could be assayed simultaneously from the same sample. Four independent experiments were averaged. Error bars indicate SD. For averaging, uptake and fusion activities of the control sample without inhibitor were set at 100%. Inhibitors were used at the following concentrations: anti-Sec17p, 1 μM; anti-Sec18p, 1 μM; Gdi1p, 2.5 μM; anti-Vam3p, 1 μM; anti-Vam7p, 1 μM; and anti-Nyv1p, 1 μM.",
    "ncbi_link": "pep4: 855949
pho8: 852092"
  },
  {
    "caption": "(B) Vacuoles and cytosols were prepared from sec18-1 and from corresponding wild-type (Wt) cells grown and spheroplasted at 23°C. The isolated vacuoles and the cytosols were exposed to heat treatment (10 min, 37°C). Standard uptake reactions were performed with vacuoles and cytosols in the indicated combinations. Control reactions were performed in the absence of ATP. Five independent experiments were averaged; the sample with vacuoles and cytosol from wild-type cells was used as the 100% reference. Error bars indicate SD. Mut, mutant.",
    "ncbi_link": "sec18: 852372"
  },
  {
    "caption": "(B  3rd instar larval fat bodies  were  stained  by BODIPY (green) for  lipid droplets  and  DAPI (blue) for  nuclei. Scale bars represent 25 µm. (B) RDH/CG2064 RNAi suppresses the enlarged  lipid droplet   phenotype in CSN2  RNAi under  DGAT1  overexpression (ppl>DGAT1) or high-fat diet conditions. (C) Quantification of the   lipid droplet  size in (B). HFD: high-fat diet. data were analyzed by one-way ANOVA with a post hoc Turkey's multiple-comparison test. Each point represents data from one fat body, and at least 30 cells were examined in each  fat body. Error bars represent ± SEM. ***: P < 0.001; **: P < 0.01; NS: non-significant.",
    "ncbi_link": "CSN2: 34225
CG2064: 35708
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": ", F 3rd instar larval fat bodies were stained  by  BODIPY  (green) for   lipid droplets and DAPI (blue) for  nuclei. Scale bars represent 25 µm. (F) RDH/CG2064 overexpression increases  lipid droplet  size in ppl>DGAT1 larvae. (G) Quantification of the  lipid droplet size in (F). data were analyzed by one-way ANOVA with a post hoc Turkey's multiple-comparison test. Each point represents data from one fat body, and at least 30 cells were examined in each fat body. Error bars represent ± SEM. ***: P < 0.001; **: P < 0.01; NS: non-significant.",
    "ncbi_link": "CG2064: 35708
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "3rd instar larval fat bodies were stained by BODIPY (green) for  lipid droplets   and DAPI  (blue) for nuclei. Scale bars represent 25 µm. (H) Relative TAG  levels in different genetic backgrounds were measured by glyceride assay  kit. For quantification, TAG levels were normalized to protein. (I) RDH/CG2064 and  CG2065 deletion does not affect lipid droplet   size under normal or high-fat diet conditions. data were analyzed by one-way ANOVA with a post hoc Turkey's multiple-comparison test. Each point represents data from one fat body, and at least 30 cells were examined in each fat body. Error bars represent ± SEM. ***: P < 0.001; **: P < 0.01; NS: non-significant.",
    "ncbi_link": "CG2064: 35708
CG2065: 35707"
  },
  {
    "caption": "(B) 3rd instar larval fat bodies  were  stained  by BODIPY (green) for lipid droplets and DAPI  (blue) for  nuclei. Overexpressing wild-type or site-mutated RDH/CG2064 increases the lipid droplet size in larvae with DGAT1  overexpression (ppl>DGAT1). Scale bar represents 25 µm.",
    "ncbi_link": "CG2064: 35708
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "(E) Lysates of Drosophila S2  cells expressing full-length Plin1 or  Plin1 with a C-terminal deletion (Plin1ΔC) were  immunoprecipitated with anti-Flag antibody and then probed by anti-GFP or anti-Flag antibody in a western blot. Plin1ΔC coimmunoprecipitated with  RDH/CG2064.",
    "ncbi_link": "Plin1: 42810"
  },
  {
    "caption": "(F) 3rd instar larval fat bodies  were  stained by BODIPY  (green) for lipid droplets  and  DAPI (blue) for nuclei. Under  high-fat conditions, RDH/CG2064 overexpression increases the lipid droplet size, and Plin2 RNAi suppresses the enlargement induced by  RDH/CG2064 overexpression. Scale bar represents 25 µm.",
    "ncbi_link": "CG2064: 35708
Plin2: 32437"
  },
  {
    "caption": "(A, B Images of  Plin2-GFP in 3rd instar larval fat body  cells  of different genotypes. Scale bar represents 25 µm. (A) CSN2 RNAi or RDH/CG2064 overexpression reduces the peripheral localization of  Plin2-GFP and increases the localization  of Plin2-GFP on small peri-nuclear lipid droplets (boxed).  DAPI (blue)  stains nuclei. White arrows indicate peripheral lipid droplet. Red arrows indicate medial lipid droplets. (B) The peripheral localization  of Plin2-GFP is greatly reduced in  fat body  cells from  larvae with  CSN2 RNAi or RDH/CG2064 overexpression. Images were taken by focusing on the periphery of fat cells.",
    "ncbi_link": "CSN2: 34225
CG2064: 35708"
  },
  {
    "caption": "C, Images of  Plin2-GFP in  3rd instar larval fat body cells of different genotypes. Scale bar represents 25 µm. (C) In fat body cells from ppl>DGAT1 larvae with CSN2 RNAi or  RDH/CG2064 overexpression, the  localization of Plin2-GFP  is greatly reduced at the periphery  and is dramatically increased on large  medial lipid droplets. White arrows indicate peripheral lipid droplet. Red arrows indicate medial lipid droplets. (D) Fluorescence intensity line plots of the images in (C). GFP intensity along the line across a lipid droplet was measured by ImageJ. In ppl>DGAT1 larvae with  CSN2 RNAi or RDH/CG2064 overexpression, Plin2-GFP localization on large  medial lipid droplets  is represented by two peaks. More than 30 lipid droplets were measured for each genotype. The plot shown is a typical image curve for the indicated genotype.",
    "ncbi_link": "CSN2: 34225
CG2064: 35708
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "(G) The  peripheral lipid droplets in larval fat body cells  from different genetic backgrounds were  stained by BODIPY (green). CSN3 RNAi or RDH/CG2064 overexpression reduces the number of peripheral lipid droplets in both wild-type and ppl>DGAT1 larvae.",
    "ncbi_link": "CG2064: 35708
CSN3: 40308
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "(A, Confocal  images of Bmm-GFP (green) in 3rd instar larval fat bodies of different genotypes. DAPI (blue) stains nuclei. Scale bar represents 25 µm. (A) Knocking down  CSN2 or overexpressing  RDH/CG2064  in animals with DGAT1 overexpression (ppl>DGAT1) decreases the level and  lipid droplet localization  of Bmm-GFP. (B) The GFP intensity along the line across a  lipid droplet  in (A) was measured by ImageJ. The  lipid droplet localization  of Bmm-GFP, represented by two peaks, is clearly visible in fat cells from ppl>DGAT1 larvae, but it is lost in  fat cells from ppl>DGAT1 larvae  with CSN2  RNAi or overexpression of RDH/CG2064. More than 30  lipid droplets of each genotype were measured. One typical image curve is shown for each genotype.",
    "ncbi_link": "CSN2: 34225
CG2064: 35708
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "F)  Confocal  images of  Bmm-GFP  (green) in 3rd instar larval fat bodies of different genotypes. DAPI  (blue)  stains nuclei. Scale bar represents 25 µm. (F) Overexpression of Plin2 decreases the level and  lipid droplet localization of Bmm-GFP in  fat cells  from  larvae  with DGAT1  overexpression. (G) GFP intensity along the line across a  lipid droplet  from (F) was measured by ImageJ. The  lipid droplet localization  of Bmm-GFP, represented by two peaks, was evident in fat cells from ppl>DGAT1 larvae, but is lost in ppl>DGAT1 larvae with overexpression of  Plin2. More than 30 lipid droplets of each genotype were measured. One typical image curve is shown for each genotype.",
    "ncbi_link": "Plin2: 32437
DGAT1: 44887
ppl: 40349"
  },
  {
    "caption": "(H) 3rd instar larval fat bodies were stained  by BODIPY (green) for   lipid droplets and  DAPI (blue) for nuclei. bmm RNAi increases the lipid droplet size in fat cells  from  larvae with  DGAT1 overexpression. Scale bar represents 25 µm.",
    "ncbi_link": "bmm: 39611
DGAT1: 44887"
  },
  {
    "caption": "(A) S2  cells expressing  RDH/CH2064-GFP  were treated with the protein synthesis inhibitor cycloheximide  (CHX) for the indicated time (h: hours). The level of RDH/CH2064-GFP was determined by  western blotting using anti-GFP antibody. Tubulin was used as loading control. (B) Quantification of the relative RDH/CH2064-GFP protein levels in (A). Error bars represent ± SEM.",
    "ncbi_link": "GFP: 
CH2064: 35708"
  },
  {
    "caption": "(C) S2 cells expressing Bmm-GFP were treated with the protein synthesis inhibitor cycloheximide (CHX) for the indicated time (h: hours). The level of Bmm-GFP was determined by western blotting  using anti-GFP antibody. Tubulin was used as loading control. (D) Quantification of the relative Bmm-GFP protein levels in (C). Error bars represent ± SEM.",
    "ncbi_link": "GFP: 
Bmm: 39611"
  },
  {
    "caption": "(B) RT-PCR analysis of the expression of NKG2D in γδ T cells isolated from indicated samples.",
    "ncbi_link": "NKG2D: 22914"
  },
  {
    "caption": "(C) RT-PCR analysis of the expression of IFN-γ and TNF-α in γδ T cells isolated from the peripheral blood of healthy controls and metastatic cancer patients. (D) RT-PCR analysis of the expression of miR-125b-5p and miR-99a-5p in γδ T cells isolated from indicated samples. (E) RT-PCR analysis of the expression of miR-181a(-5p and -2-3p) in γδ T cells isolated from indicated samples.",
    "ncbi_link": "IFN-γ: 3458
miR-125b-5p: 406911
miR-181a: 406954
miR-99a-5p: 407055
TNF-α: 7124"
  },
  {
    "caption": "(A) RT-PCR analysis of the expression of miR-181a(-5p and -2-3p) in γδ T cells isolated from thymic biopsies, cultured for 11 days with IL-7 or IL-2 (n=12-15 independent biological samples). (B) RT-PCR analysis of the expression of miR-181a(-5p and -2-3p) in γδ T cells freshly isolated from thymic biopsies (Thymus) and PBLs (n=6-14 independent biological samples).",
    "ncbi_link": "miR-181a: 406954"
  },
  {
    "caption": "(C-D) RT-PCR analysis of the expression of miR-181a(-5p and -2-3p) in γδ T cells isolated from thymus (C) or from PBLs (D) and cultured with the indicated cytokines, respectively for 11 days (C) or for 4-6 days (D). When indicated, γδ PBLs were also co-cultured with an anti-TGF-β blocking antibody. Data are normalized to the value obtained in IL-7 cultures (n=4-10 independent biological samples).",
    "ncbi_link": "miR-181a: 406954"
  },
  {
    "caption": "(E-F) RT-PCR analysis of the expression of miR-181a(-5p and -2-3p) versus FACS analysis of the expression of TNF-α (left panel), IFN-γ (middle panel) and NKGD2 (right panel) in γδ T cells isolated from thymus (E) and PBLs (F). Samples were either freshly isolated or cultured for 11 days (γδ thymocytes) or for 6 days (γδ PBLs) with the indicated cytokines (n=5 independent biological samples).",
    "ncbi_link": "miR-181a: 406954"
  },
  {
    "caption": "(D) FACS analysis of the expression of Annexin V in miR-181a versus empty transduced (GFP+) and untransduced (GFP-) γδ thymocytes, cultured with IL-7 plus IL-2 for 11 days (n=5 independent biological samples).",
    "ncbi_link": "GFP: 
miR-181a: 406954"
  },
  {
    "caption": "(E) RT-PCR analysis of the expression of Bcl2 and Bcl-xL (normalized to the values obtained with the empty virus) in transduced (GFP+) γδ thymocytes, cultured with IL-7 plus IL-2 for 11 days (n=5 independent biological samples).",
    "ncbi_link": "GFP: 
Bcl-xL: 572
Bcl2: 596"
  },
  {
    "caption": "(F) FACS-derived expression of indicated surface and intracellular markers in miR-181a versus empty transduced (GFP+) and untransduced (GFP-) γδ T thymocytes, cultured with IL-7 plus IL-2 for 11 days (n=7-11 independent biological samples).",
    "ncbi_link": "GFP: 
miR-181a: 406954"
  },
  {
    "caption": "(B) RT-PCR analysis of the expression of the indicated genes associated with Mapk, Notch, Irf4 or Stat1 signaling in sorted GFP+ γδ thymocytes transduced with empty or miR-181a viral vector. Data are normalized to the value obtained with the empty virus. Samples were cultured with IL-7 plus IL-2 for 11 days (n=3-5 independent biological samples).",
    "ncbi_link": "GFP: 
Irf4: 3662
Mapk: 10746
miR-181a: 406954
Notch: 4853
Stat1: 6772"
  },
  {
    "caption": "(C) Dual luciferase reporter assay performed to verify binding between miR-181a and Map3k2, Notch2, Irf4 or Stat1 mRNA. HEK293 T cells were co-transfected with a pmirGLO Dual-Luciferase miRNA Target Expression Vector containing either the WT or mutated (Mut) 3′ UTR target sites plus miR-181a. A negative construct (without miR-181a binding sites) was included. Firefly/Renilla ratios were normalized to those obtained for the empty vector (n=4 independent biological samples).",
    "ncbi_link": "Luciferase: 
Irf4: 3662
Map3k2: 10746
miR-181a: 406954
Notch2: 4853
Stat1: 6772"
  },
  {
    "caption": "(E-G) RT-PCR analysis in circulating γδ T cells of Map3k2 or Notch2 expression (E), Nkg2d or Tnfa expression (F), and NKG2D or TNF-α protein expression (G) after siRNA-mediated knockdown of Map3k2 or Notch2. In each experiment, a control condition was also used where a nontargeting negative control siRNA was transfected. γδ were cultured with IL-7 for 4 days (n=6 independent biological samples).",
    "ncbi_link": "Nkg2d: 22914
Map3k2: 10746
Notch2: 4853
Tnfa: 7124"
  },
  {
    "caption": "HEK293 cells were transfected with α11.2, α2δ-1, and β2A and cultured for 22-24h before cell attached patch recording in 110 mM Ba2+. Single CaV1.2 channel recordings of CaV1.2 WT and K1647A. Holding potential (HP) was -80 mV and test potential (TP) 0 mV. Shown are 10 consecutive sweeps from representative experiments (see Fig. EV 4 for more sweeps). Dot plots and means + SEM for availability (i.e., likelihood that a sweep had at least one event; c), NPo (d), Po (e), unitary current amplitude i (e), and the mean of the current of a single channel at any point in time calculated from the ensemble averages of each experiment (g) (**p<0.01, ***p<0.001 compared to WT; one-way ANOVA with Bonferroni post-hoc test (c) or Welch ANOVA with Tamhane T2 test (d-g); n = 7 to 35 see Table 5 for more details).",
    "ncbi_link": "α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "HEK293 cells were transfected with α11.2, α2δ-1, and β2A plus, if indicated, α-actinin-1 before cell attached patch recording. Representative single CaV1.2 channel recordings of WT CaV1.2 alone or with WT or E847K/E851K mutant α-actinin-1. Mean assemble averages for all experiments for each combination. Dot plots and means + SEM for availability (c), NPo (d), Po (e), unitary current amplitude i (f), and the mean of the current of a single channel calculated from the ensemble averages of each experiment (g) (*p<0.05, **p<0.01, ****p<0.001; unpaired t-test; n = 13 to 35; see Table 6 for more details).",
    "ncbi_link": "α-actinin-1: 87
α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "HEK293 cells were transfected with α11.2 with the K1647E mutation, α2δ-1, and β2A plus α-actinin-1 WT or E847K/E851K before cell attached patch recording. Representative single CaV1.2 channel recordings of CaV1.2 K1647E with WT or E847K/E851K α-actinin-1. Mean assemble averages for all experiments for both combinations. Dot plots and means + SEM for availability (c), NPo (d), Po (e), unitary current amplitude i (f), and mean of the current of a single channel calculated from the ensemble averages of each experiment (g) (**p<0.01; unpaired t-test; n = 16 to 30; see Suppl. Fig. 8 and Table 6 for more details).",
    "ncbi_link": "α-actinin-1: 87
α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "HEK293 cells were transfected with WT α11.2, α2δ-1, and β2A + WT α-actinin-1 and cultured for 22-24h before surface biotinylation. Shown are representative immunoblots of NeutrAvidin pull-down samples (from lysate containing 600 μg protein) and total lysate samples containing 20 μg protein. α11.2 was detected with an antibody against its HA tag (top), which is present in all constructs used throughout this work. Pull-down and lysate samples are from the same blot but different exposures because signals from lysate samples were much stronger than from pull-down samples. Immunoblotting for vinculin (middle) and tubulin (bottom) indicated that comparable amounts of these intracellular control proteins were present in lysate samples. Their absence in pull-down samples as seen on the same blots showed that these prominent intracellular proteins did not undergo biotinylation as control for membrane integrity during surface biotinylation. Bar graph shows means + SEM of the pull-down immunosignals in mutants relative to surface labelling of control α11.2 samples lacking α-actinin-1 co-expression (mean set to 100%; see Methods; **p<0.01 two-tailed t-test; n = 7).",
    "ncbi_link": "α-actinin-1: 87
α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "HEK293 cells were transfected with WT or K1647E mutant α11.2, α2δ-1, and β2A, and WT or E847K/E851K mutant α-actinin-1, or CFP alone as negative control and cultured for 22-24h before surface biotinylation. Shown are representative immunoblots of pull-down and lysate samples as in (a). Bar graph shows means + SEM of the pull-down immunosignals in mutants relative to surface labelling in the WT/WT control (mean set to 100%; see Methods). **p<0.01, ***p < 0.001; one-way ANOVA with Tukey post hoc test; n = 4-5).",
    "ncbi_link": "CFP: 
α-actinin-1: 87
α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "HEK293 cells were transfected with α11.2, α2δ-1, and β2A before whole cell patch recording in 20 mM Ba2+. Representative current traces of the first 2 ms obtained from recordings upon depolarizations from a holding potential of -80 mV to the indicated potentials (the voltage protocol is schematized in the upper left corner). Representative current traces upon step depolarizations to the reversal potential (Erev) for 20 ms to obtain movement of the ON-gating charges (Qon), and subsequent to -50 mV for 10 ms to obtain tail currents (Itail). Insets: magnifications of exemplary Qon for CaV1.2 WT, K1647A, Y1649A, I1654A, F1658A and K1662E. Plots of Itail (in this panel corrected for variations in cell capacitance) versus total detectable charge transfer for Qon. Slopes of regression curves are strongly reduced for CaV1.2 K1647A, Y1649A and I1654A versus WT (see Table 7 for more details). Dot plots and means + SEM of Qon (in this panel corrected for variations in cell capacitance; *p<0.05; **p<0.01; one-way ANOVA with Bonferroni post-hoc test; n = 13-18; see Table 7 for more details). The reduction in slope of the regression curve of combined population data for K1647A, Y1649A and I1654A versus WT indicates reduced coupling of Itail with Qon when α-actinin binding to the IQ motif is diminished.",
    "ncbi_link": "α11.2: 24239
α2δ-1: 100009105
β2A: 116600"
  },
  {
    "caption": "(D) IF of DAXX and ATRX in PN5 zygotes upon siRNA-mediated knockdown of Daxx (n=14) or with control siRNAs (n=8). Data information: All panels: images of paternal and maternal pronuclei at given stage/condition are from same zygote. Yellow dashed circles represent the contours of the pronuclei. All scale bars, 10µm.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(E) IF of DAXX and ATRX in control (n=15) and Atrxm-z+ (n=14) PN5 zygotes. Data information: All panels: images of paternal and maternal pronuclei at given stage/condition are from same zygote. Yellow dashed circles represent the contours of the pronuclei. All scale bars, 10µm.",
    "ncbi_link": "Atrx: 22589"
  },
  {
    "caption": "(A) IF of DAXX and EZH2 in paternal pronuclei of Ezh1m-z+ (n=5), Ezh2m-z+ (n=3) and Ezh1m-z+; Ezh2m-z+ (n=4) late zygotes. Yellow dashed circles represent the contours of the pronuclei. Data information: All scale bars, 10µm.",
    "ncbi_link": "Ezh1: 14055
Ezh2: 14056"
  },
  {
    "caption": "(C) IF of DAXX in wild type (n=30), Ring1m-z+ (n=12), Rnf2m-z+ (n=11) and Ring1m-z+; Rnf2m-z+ (n=12) paternal pronuclei of PN5 zygotes. Data information: All scale bars, 10µm.",
    "ncbi_link": "Ring1: 19763
Rnf2: 19821"
  },
  {
    "caption": "(C) Occupancy (% of IP-ed DNA / input DNA) of GAL4DBDCBX2, RNF2, DAXXMycHis, H3.3, and H3 proteins at 5×UAS site as measured by ChIP-qPCR of chromatin from HEK2935xUAS cells. Data are means ± SEM (n = 3).",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
DAXX: 13163
GAL4: 855828
H3.3: 3020///3021
H3: 440093///440686///391769///340096///3020///8290///3021
RNF2: 6045"
  },
  {
    "caption": "(E) ChIP-seq analysis of HEK2935xUAS cells expressing full length GAL4DBDCBX2.1 and DaxxMycHis showing CBX2.1 dependent recruitment of DAXX to promoters of CCND2 and RUNX1 genes.",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
CCND2: 894
Daxx: 13163
DAXX: 13163
GAL4: 855828
RUNX1: 861"
  },
  {
    "caption": "(F) ChIP-seq analysis of GAL4DBDCBX2.1 occupancy in HEK2935xUAS cells expressing DAXXMycHis (X-axis) or GAL4DBDCBX2.1 and DAXXMycHis (Y-axis), showing (log2) enrichment for GAL4DBDCBX2.1 at many TSSs (± 1 kb) in cells expressing the CBX2.1 protein (Y-axis).",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
DAXX: 13163
GAL4: 855828"
  },
  {
    "caption": "(G) ChIP-seq analysis of GAL4DBDCBX2.1 versus DAXXMycHis occupancy in HEK2935xUAS cells expressing GAL4DBDCBX2.1 and DAXXMycHis, revealing very comparable enrichment levels (log2) of both proteins at TSSs. TSSs highlighted in red show enrichment with anti-Myc antibody independently of GAL4DBDCBX2.1 occupancy.",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
DAXX: 13163
GAL4: 855828"
  },
  {
    "caption": "(H) ChIP-seq analysis of DAXXMycHis occupancy in HEK2935xUAS cells expressing DAXXMycHis (X-axis) versus GAL4DBDCBX2.1 and DAXXMycHis (Y-axis) showing strong enrichment (log2) for DAXXMycHis at many TSSs of genes, but only when both proteins are expressed (Y-axis), indicating that CBX2.1 targets DAXX to chromatin. TSSs highlighted in red show enrichment with anti-Myc antibody independently of GAL4DBDCBX2.1 occupancy.",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
DAXX: 13163
GAL4: 855828"
  },
  {
    "caption": "(B) ChIP-qPCR analyses of HEK2935xUAS cells co-expressing GAL4DBDCBX2.1 either with DAXXMycHis or DAXXΔSIM1/2MycHis. Data are means ± SEM (n = 3).",
    "ncbi_link": "His: 
Myc: 
CBX2: 84733
DAXX: 13163
GAL4: 855828"
  },
  {
    "caption": "(C) IF of EGFP and DAXX in Daxxm-z+ PN5 zygotes micro-injected with Daxx-EGFP or DaxxΔSIM1/2-EGFP mRNA (100ng/µl). Data information: Scale bars, 10µm.",
    "ncbi_link": "EGFP: 
Daxx: 13163"
  },
  {
    "caption": "(D) Left: Boxplot displaying EGFP signal intensities at PCH relative to euchromatin in Daxxm-z+ zygotes micro-injected with Daxx-EGFP or DaxxΔSIM1/2-EGFP mRNA. Right: Boxplot displaying signal intensity of EGFP at euchromatin in same samples. In boxplots, the enter lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 3 times. ***P<0.001, N.S.: no statistical difference, P>0.05, t-test.",
    "ncbi_link": "EGFP: 
Daxx: 13163"
  },
  {
    "caption": "(F) Ni-pulldown of 6xHisSUMO1/2/3-conjugated proteins from HEK293 extracts expressing 6xHis-tagged SUMO1, SUMO2 or SUMO3 in combination with CBX2-EGFP. CBX2 and SUMO-conjugated CBX2 were detected with an anti-GFP antibody.",
    "ncbi_link": "EGFP: 
His: 
CBX2: 84733
SUMO1: 7341
SUMO2: 6613
SUMO3: 6612"
  },
  {
    "caption": "(G) Ni-pulldown of 6xHis-SUMO2 conjugated proteins from HEK293 extracts transiently co-expressing 6xHis-SUMO2 with CBX2-EGFP or CBX24KR-EGFP. Detection of CBX2",
    "ncbi_link": "EGFP: 
His: 
CBX2: 12416
SUMO2: 6613"
  },
  {
    "caption": "(H) IF of DAXX and EGFP in wild-type PN5 zygotes, micro-injected with Cbx2 or Cbx24KR-EGFP mRNA (100ng/µl). Data information: Scale bars, 10µm.",
    "ncbi_link": "EGFP: 
Cbx2: 12416"
  },
  {
    "caption": "(I) Left: Boxplot displaying signal intensity of DAXX at PCH relative to mean intensity at pat-PCH in wild-type zygotes micro-injected with Cbx2 or Cbx24KR-EGFP mRNA. Right: Absolute intensities of EGFP in same samples. In boxplots, the enter lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 2 times. ***P<0.001, t-test.",
    "ncbi_link": "EGFP: 
Cbx2: 12416"
  },
  {
    "caption": "(A) IF of DAXX and ATRX in PN5 stage pronuclei of wild-type (n=19), Hp1βm-z+ (n=10) and Suv39h2m-z+ (n=9) zygotes. Data information: Panels Paternal and maternal pronuclei of a given condition originate from same zygotes. All scale bars 10µm.",
    "ncbi_link": "Hp1β: 12412
Suv39h2: 64707"
  },
  {
    "caption": "(B) Boxplots displaying signal intensities of DAXX or ATRX at pat- and mat-PCH in wild-type (n=5) and Hp1βm-z+ (n=10) mouse zygotes at PN5. In boxplots, the enter lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 2 times. *P<0.05, **P<0.01, t-test.",
    "ncbi_link": "Hp1β: 12412"
  },
  {
    "caption": "(C) IF of DAXX in PN5 stage pronuclei of zygotes expressing CBX2-EGFP (n=9) or CBX2F12A-EGFP (n=17). mRNAs (100ng/µl) were injected into mouse PN2 stage zygotes. Yellow dashed circles represent the contours of the pronuclei.. Data information: Panels C: Paternal and maternal pronuclei of a given condition originate from same zygotes. All scale bars 10µm.",
    "ncbi_link": "EGFP: 
CBX2: 84733"
  },
  {
    "caption": "(A) Developmental progression of Daxxm+z+, Daxxm-z+ and Daxxm-z- early embryos.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(D) Still images of time-lapse imaging of the first cleavage division in wild-type and maternally deficient zygotes expressing H2B-mCherry. Time points represent minutes after prometaphase. Lagging chromosomes and micronuclei are indicated by yellow arrowheads. Data information: All scale bars 10µm.",
    "ncbi_link": "H2B: 
mCherry: "
  },
  {
    "caption": "(F) IF of 5-methyl and 5-hydroxy-methyl cytosine staining of wild-type (n=42), Daxxm-z+ (n=14) and Ring1m-z+; Rnf2m-z+ (n=6) zygotes with lagging chromosomes. Yellow arrowheads indicate lagging chromosomes. Data information: All scale bars 10µm.",
    "ncbi_link": "Daxx: 13163
Ring1: 19763
Rnf2: 19821"
  },
  {
    "caption": "(G) DNA-FISH for major (green) and minor (red) satellites on cleavage chromosomes of a Daxxm-z+ zygote with a chromosome broken within the major satellite region. Data information: All scale bars 10µm.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(H) H3.3-EGFP live-imaging signal in pat- and mat-PCH of control Daxxm+z+ (n=18), Daxxm-z+ (n=8) and Ring1m-z+; Rnf2m-z+ (n=12) zygotes. Scale bar 10µm.",
    "ncbi_link": "Daxx: 13163
Ring1: 19763
Rnf2: 19821"
  },
  {
    "caption": "(I) Left: IF of endogenous H3 and ATRX at pat-PCH in control and Daxxm-z+ PN5 zygotes. Right: Fluorescence intensity profiles of H3 and ATRX along white line in left panel at pat-PCH of zygotes. Scale bars 5 µm. Data information: All scale bars 10µm.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(J) Boxplot displaying H3 signal intensity at pat-PCH of Daxxm+z+ and Daxxm-z+ PN5 zygotes. In boxplots, the enter lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 2 times. ***P<0.001, t-test, n=12 for both groups.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(K) IP of DAXX-EGFP and DAXXR244A-EGFP proteins with an anti-GFP antibody from nuclear extract of HEK293 cells. Immuno-blot detection was performed with antibodies recognizing GFP, histone variant H3.3 and CBX2.",
    "ncbi_link": "EGFP: 
DAXX: 13163"
  },
  {
    "caption": "(L) Percentage of Daxxm-z+ zygotes with lagging chromosomes following injection of Tubulin-EGFP, Daxx-EGFP or DaxxR244A-EGFP mRNAs (20 or 100 ng/µl) at PN2/3 stage. Data represent mean ± s.e.m. (n ≥2 injection experiments). *** P<0.001 High Daxx-EGFP versus other 3 groups; Fisher's exact test (on pooled embryos).",
    "ncbi_link": "EGFP: 
Tubulin: 
Daxx: 13163"
  },
  {
    "caption": "(M) Left: IF of EGFP and endogenous H3 at pat-PCH in Daxxm-z+ PN5 zygotes expressing DAXX-EGFP or DAXXR244A-EGFP or nothing exogenously. Right: Fluorescence intensity profiles of H3 and EGFP along white lines in left panels at pat-PCH of zygotes. Scale bars 5 µm. Data information: All scale bars 10µm.",
    "ncbi_link": "EGFP: 
Daxx: 13163
DAXX: 13163"
  },
  {
    "caption": "(N) Boxplot displaying 3D quantification of H3 signal intensity at pat-PCH in Daxxm-z+ zygotes expressing exogenous DAXX-EGFP (n=14) or DAXXR244A-EGFP (n=13). In boxplots, the enter lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 2-3 times. ***P<0.001 Daxx-EGFP versus other 2 groups; t-test.",
    "ncbi_link": "EGFP: 
Daxx: 13163
DAXX: 13163"
  },
  {
    "caption": "(A) RNA FISH of forward and reverse strand major satellite sequences in Daxxm+z+ and Daxxm-z+ PN5 zygotes. Scale bars, 10µm.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(B) Box plots indicating the foci number (left) and total intensity (right) of forward (top) and reverse (bottom) transcription as measured by RNA FISH on 3D paternal pronuclei in Daxxm+z+ and Daxxm-z+ PN5 zygotes. Lower hinge, central line and upper hinge in boxplots represent 25th, 50th (median) and 75th percentiles respectively. Upper/lower whiskers extend to the largest/smallest values no further than 1.5 * IQR from the upper/lower hinge, where IQR is inter-quartile range or distance between 25th and 75th percentiles. Datapoints are indicated by circles. Experiments were replicated 3 times. ***P<0.001; t-test.",
    "ncbi_link": "Daxx: 13163"
  },
  {
    "caption": "(J) Boxplot showing FC (log2) in gene expression between Daxx deficient and control MII oocytes for five groups of genes classified according to FC (log2) in gene expression between Ring1 Rnf2 deficient and control GV oocytes. Boxplots were created and number of genes used for each boxplot is displayed below. Expression changes were estimated using 3 biological replicates for each condition. Statistical significance was estimated using two-sided t-tests.",
    "ncbi_link": "Daxx: 13163
Ring1: 19763
Rnf2: 19821"
  },
  {
    "caption": "(A)   Oil Red O staining   of mouse BAs differentiated  from normal or EP3-deficient brown pre-adipocytes. Scale bar: 50 μm. (B) Mean  lipid droplet area of differentiated BAs  from normal or EP3-deficient brown  pre-adipocytes. *P < 0.05 vs WT (n = 6). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by Mann-Whitney U tests (B, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(D) Representative image of hematoxylin  and eosin  (H&E) staining  for iBAT  from EP3F/F and  EP3F/FMyf5Cre mice. Scale bar: 50 μm. (E) Mean adipocyte area of BAs  in iBAT  from  EP3F/F and EP3F/FMyf5Cre mice  (n = 8). Data information: Data represent the mean ± standard error of mean (SEM). Data are pooled from two independent experiments with biological replicates Statistical significance was evaluated by Mann-Whitney U tests E, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "Cre: 2777477
Myf5: 17877
EP3: 19218"
  },
  {
    "caption": "(K) Representative image of H&E staining  of iBAT  from EP3F/F and EP3F/FMyf5Cre mice  fed HFD. Scale bar: 50 μm. (L) Mean adipocyte  area of BAs  in iBAT  from EP3F/F and EP3F/FMyf5Cre mice  fed HFD (n = 8). Data information: Data represent the mean ± standard error of mean (SEM). Data are pooled from two independent experiments with biological replicates L, Statistical significance was evaluated by Mann-Whitney U tests L, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "Cre: 2777477
Myf5: 17877
EP3: 19218"
  },
  {
    "caption": "(A) N6-methyladenosine (m6A) modification levels of mRNAs in normal and EP3-deficient brown pre-adipocytes  with or without brown adipogenesis induction, detected by m6A RNA Methylation  Quantification Kit (Colorimetric) (n = 4-6). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by unpaired two-tailed student's t test (A *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(B)  qRT-PCR analysis of the relative mRNA levels of m6A  writers (METTL3, METTL4, METTL14  and WTAP) and erasers (FTO  and ALKBH5) in normal and EP3-deficient brown pre-adipocytes  with or without brown adipogenesis induction (n = 6-9). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by unpaired two-tailed student's t test B, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "ALKBH5: 268420
FTO: 26383
METTL14: 210529
METTL3: 56335
METTL4: 76781
EP3: 19218
WTAP: 60532"
  },
  {
    "caption": "(C) Western blotting analysis of m6A  writers and erasers in normal and EP3-deficient brown pre-adipocytes with or without brown adipogenesis induction.",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(E) Western blotting analysis of WTAP  in iBAT  from EP3F/F and EP3F/FMyf5Cre mice  fed HFD  for 1 week.",
    "ncbi_link": "Cre: 2777477
Myf5: 17877
EP3: 19218"
  },
  {
    "caption": "(F)  Western blotting analysis of WTAP  in BAs differentiated  from EP3γ-expressed brown pre-adipocytes.",
    "ncbi_link": "EP3γ: 19218"
  },
  {
    "caption": "(G) Relative mRNA levels of WTAP  gene in BAs differentiated  from EP3γ-expressed brown pre-adipocytes  detected by RT-qPCR (n = 6-7). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates G, Statistical significance was evaluated by two-way ANOVA followed by Tukey's test for post-hoc comparisons (G, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "EP3γ: 19218
WTAP: 60532"
  },
  {
    "caption": "(H) qRT-PCR analysis of the relative mRNA levels of EP3γ  gene in BAs  differentiated from EP3γ-expressed EP3-/- brown pre-adipocytes after transfection with WTAP  siRNA (n = 8). (I) qRT-PCR analysis of the relative mRNA levels of WTAP  gene in BAs  differentiated from EP3γ-expressed EP3-/- brown pre-adipocytes after transfection with WTAP  siRNA (n = 8). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by unpaired two-tailed student's t test H), two-way ANOVA followed by Tukey's test for post-hoc comparisons I, *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "EP3γ: 19218
EP3: 19218
WTAP: 60532"
  },
  {
    "caption": "(J) Representative picture of  oil red O-stained BAs differentiated  from EP3γ-expressed EP3-/- brown pre-adipocytes with WTAP  siRNA treatment. Scale bar: 50 μm.",
    "ncbi_link": "EP3: 19218
EP3γ: 19218
WTAP: 60532"
  },
  {
    "caption": "(K-Q) qRT-PCR analysis of the relative mRNA levels of brown marker genes in BAs  differentiated from EP3γ-expressed EP3-/- brown pre-adipocytes after transfection with WTAP  siRNA (n = 6-8). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by two-way ANOVA followed by Tukey's test for post-hoc comparisons K-Q). *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "EP3: 19218
EP3γ: 19218
WTAP: 60532"
  },
  {
    "caption": "(A) Western blotting analysis of ubiquitination  of WTAP  in the control and EP3-deficient brown pre-adipocytes with or without sulprostone  treatment. Data information: Data are representative of two independent experiments with biological replicates",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(B) Western blotting  analysis of ERK1/2 phosphorylation  in the control and EP3-deficient  brown pre-adipocytes. Data information: Data are representative of two independent experiments with biological replicates",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(E) Analysis of PKA activity  in the control and EP3-deficient  brown pre-adipocytes (n = 4). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(F) Effect of PKA  inhibitor, H89, on ubiquitin-dependent degradation of WTAP  in EP3-/- brown pre-adipocytes. Data information: Data are representative of two independent experiments with biological replicates",
    "ncbi_link": "EP3: 19218"
  },
  {
    "caption": "(G) Effect of ERK1/2 phosphorylation  site mutation (HA-WTAP-2A) on EP3-mediated ubiquitin-dependent degradation  of WTAP  in brown pre-adipocytes. Data information: Data are representative of two independent experiments with biological replicates",
    "ncbi_link": "HA: 
EP3: 19218
WTAP: 60532"
  },
  {
    "caption": "(C)  Time course analysis of the relative mRNA levels of EP3  receptors in hESC-derived BAs  during BA differentiation  detected by RT-qPCR (n = 7-8). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates (C, Statistical significance was evaluated by Welch ANOVA test followed by Tamhane's T2 test for post-hoc comparisons (C) *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "EP3: 5733"
  },
  {
    "caption": "(F) Effect of H89  on WTAP  mRNA expression  in hESC-derived BAs  treated with L798106  (n = 6-7). (G) Effect of H89  on ZNF410  mRNA expression  in hESC-derived BAs  treated with L798106  (n = 8). Data information: Data represent the mean ± standard error of mean (SEM). Data are representative of two independent experiments with biological replicates Statistical significance was evaluated by , two-way ANOVA followed by Tukey's test for multiple comparisons F, G). *P < 0.05, **P < 0.01, ***P < 0.001 and ns, not significant (P > 0.05).",
    "ncbi_link": "WTAP: 9589
ZNF410: 57862"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Home cage-activity test (A). Voluntary locomotor activities in the home cages were monitored for a week. Data of dark (left) and light (right) phases are indicated.",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Open-field test (B)",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Acoustic startle response (C)",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Prepulse-inhibition test (D)",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in , Morris water-maze test (E) where data in hidden test (escape latency and moving speed, path length and no movement time) and probe test (path length) are shown",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Y-maze test (F).",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Fear-conditioning test (G). Results of contextual (left) and cued (right) tests are shown.",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Ldb2 KO mice (red, n = 10-11) were compared to control (blue, n = 10-11) in Hot-plate test (H).",
    "ncbi_link": "Ldb2: 16826"
  },
  {
    "caption": "Results of coimmunoprecipitation between overexpressed LDB2 and interaction candidates LDB2 vs. LDB2 (A) LDB2 (WT, T83N or P170L) and candidate interactors were tagged with Flag and HA, respectively. HEK293T cells were transfected with the Flag-construct and HA-construct indicated. After Flag-LDB2 was immunoprecipitated with a Flag antibody, the immunocomplexes were analyzed with western blotting with Flag and HA antibodies. The input samples (input) were also analyzed. Green and black arrowhead indicate positions for Flag-Ldb2 and HA-proteins, respectively.",
    "ncbi_link": "Flag: 
HA: 
LDB2: 9079"
  },
  {
    "caption": "Results of coimmunoprecipitation between overexpressed LDB2 and interaction candidates LDB2 vs. LHX2 (B) LDB2 (WT, T83N or P170L) and candidate interactors were tagged with Flag and HA, respectively. HEK293T cells were transfected with the Flag-construct and HA-construct indicated. After Flag-LDB2 was immunoprecipitated with a Flag antibody, the immunocomplexes were analyzed with western blotting with Flag and HA antibodies. The input samples (input) were also analyzed. Green and black arrowhead indicate positions for Flag-Ldb2 and HA-proteins, respectively.",
    "ncbi_link": "Flag: 
HA: 
LDB2: 9079"
  },
  {
    "caption": "Results of coimmunoprecipitation between overexpressed LDB2 and interaction candidates LDB2 vs. LMO2/3/4 (C) LDB2 (WT, T83N or P170L) and candidate interactors were tagged with Flag and HA, respectively. HEK293T cells were transfected with the Flag-construct and HA-construct indicated. After Flag-LDB2 was immunoprecipitated with a Flag antibody, the immunocomplexes were analyzed with western blotting with Flag and HA antibodies. The input samples (input) were also analyzed. Green and black arrowhead indicate positions for Flag-Ldb2 and HA-proteins, respectively.",
    "ncbi_link": "Flag: 
HA: 
LDB2: 9079"
  },
  {
    "caption": "Results of coimmunoprecipitation between overexpressed LDB2 and interaction candidates , LDB2 vs. SSBP2/3/4 (D) LDB2 (WT, T83N or P170L) and candidate interactors were tagged with Flag and HA, respectively. HEK293T cells were transfected with the Flag-construct and HA-construct indicated. After Flag-LDB2 was immunoprecipitated with a Flag antibody, the immunocomplexes were analyzed with western blotting with Flag and HA antibodies. The input samples (input) were also analyzed. Green and black arrowhead indicate positions for Flag-Ldb2 and HA-proteins, respectively.",
    "ncbi_link": "Flag: 
HA: 
LDB2: 9079"
  },
  {
    "caption": "Results of coimmunoprecipitation between overexpressed LDB2 and interaction candidates LDB2 vs. RLIM (E). LDB2 (WT, T83N or P170L) and candidate interactors were tagged with Flag and HA, respectively. HEK293T cells were transfected with the Flag-construct and HA-construct indicated. After Flag-LDB2 was immunoprecipitated with a Flag antibody, the immunocomplexes were analyzed with western blotting with Flag and HA antibodies. The input samples (input) were also analyzed. Green and black arrowhead indicate positions for Flag-Ldb2 and HA-proteins, respectively.",
    "ncbi_link": "Flag: 
HA: 
LDB2: 9079"
  },
  {
    "caption": "C. Overlap of ChIP-seq peaks of LDB2 in neurosphere cells and ChIP-seq peaks of EGR1 in human cultured cell lines ECC1 and K562, at ARC",
    "ncbi_link": "ARC: 23237"
  },
  {
    "caption": "F. In vivo tumor growth of A673 EV or GYS1-KO injected in the flanks of athymic nude mice. Values are presented as mean +/- standard error (n=8 biological replicates per group). ****P<0.0001, analyzed by two-tailed t-test.",
    "ncbi_link": "GYS1: 2997"
  },
  {
    "caption": "P. (Top) Western blot showing confirmation of laforin overexpression in A673 xenograft tumors. (Bottom) Tumor growth of xenografts of A673 empty vector (EV) and laforin overexpression (LAOE). Values are presented as mean +/- standard error (n=8 biological replicates per group). ****P<0.0001, analyzed by two-tailed t-test.",
    "ncbi_link": "laforin: 7957"
  },
  {
    "caption": "(J) Representative western blot  analysis and densitometry of zcIs13[hsp-6p::GFP] expression  in control, gas-1(fc21) and gas-1(fc21); cest-2.2 O/E animals (one-way ANOVA with Holm-Sidak's correction, n=3 biological replicates). Data information: , bars represent mean± SEM Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
gas-1: 181646"
  },
  {
    "caption": "(M)  Immunoblot and statistical analysis of zcIs13[hsp-6p::GFP] expression  in control and nuo-6(qm200) animals fed with empty vector (C RNAi) and cest-2.2 RNAi bacteria (unpaired t-test, n=3 biological replicates). Data information: bars represent mean± SEM Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
nuo-6: 172438"
  },
  {
    "caption": "(A) Representative images of 5-day-old wt,   gas-1(fc21) and gas-1(fc21); cest-2.2 O/E mutant animals  stained  with Oil Red O (ORO) (scale bar= full image-100 μm;  hindgut  magnification-20 μm). (B) Quantification of hindgut (left panel), foregut  (center panel) and whole body (right panel) of 5-day-old wt, gas-1(fc21) and gas-1(fc21); cest-2.2  O/E mutant  nematodes stained with  ORO (one-way ANOVA with Tukey's multiple comparison test, n=18-26 animals). (C) Quantification of mean intensity of ORO staining   in the hindgut of wt, gas-1(fc21) and gas-1(fc21); cest-2.2  O/E mutant nematodes  at different time points, starting from L4 stage (one-way ANOVA with Dunnett's post hoc correction, n=18-26 animals). (D) Mean intensity of ORO staining in the whole body  of 5-day-old wt, gas-1(fc21) and gas-1(fc21);  cest-2.2 O/E mutant nematodes  plotted against body area. Data information: , bars represent mean ±SEM points represent mean ±SEM. Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
gas-1: 181646"
  },
  {
    "caption": "(E) Representative images of wt,  cest-2.2 O/E and cest-2.2 (lf) animals  stained  with  ORO. Arrows indicate mislocalized lipid droplets. (F) Quantification (mean intensity ± SEM) of  ORO staining in hindgut  (left panel), foregut (center panel) and whole body (right panel) of 5-day-old  nematodes (one-way ANOVA with Dunnett's post hoc correction, n=11-17 animals). Data information: , bars represent mean ±SEM Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917"
  },
  {
    "caption": "(G) Representative images of 5-day-old wt, gas-1(fc21) and gas-1(fc21); cest-2.2 O/E mutant animals stained with  LipidTOX (scale bar= 100 μm). (H) Statistical analysis of whole-body LipidTOX intensity of 5-day-old nematodes (ordinary one-way ANOVA with Tukey's multiple comparisons test, n=25-37 animals). Data information: bars represent mean ±SEM ; Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
gas-1: 181646"
  },
  {
    "caption": "(K) Representative  thin layer chromatography (TLC) plate of samples from 5-day-old gas-1(fc21) and gas-1(fc21); cest-2.2 O/E mutant nematodes. (L) Densitometry of  TLC-separated free fatty acids (FFA) across three biological replicates in 5-day-old mutant animals. Data information: bars represent mean ±SEM ; Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
gas-1: 181646"
  },
  {
    "caption": "(N) Sum of TLC-separated  FFA of 5-day old animals (n=5 biological replicates). (O) Quantification of individual FFA detected after  TLC  separation in 5-day-old gas-1(fc21) and  gas-1(fc21); cest-2.2 O/E mutant nematodes (n=5 biological replicates, n.d.= not detected). Data information: bars represent mean ±SEM ; Across experiments, p value summary is ns= not significant, *p<0.05, **p < 0.01; ***p < 0.001, ****p<0.0001.",
    "ncbi_link": "cest-2.2: 179917
gas-1: 181646"
  },
  {
    "caption": "ISRE-luciferase reporter assay in 293T cells infected with BTV-8 or mock-infected (Control) and treated with 1000 U/ml of universal-IFN Luminescence fold induction was measured at different time points p.i. Mean luciferase activity fold inductions in control or BTV-infected in three experiments are presented. *",
    "ncbi_link": "ISRE: "
  },
  {
    "caption": "GAS-luciferase reporter assay in Vero cells infected with BTV-8 or mock-infected (Control) and treated wit 5 ng/ml of IFN-γ. Luminescence fold induction was measured at different time points p.i. Mean luciferase activity fold inductions in control or BTV-infected in three experiments are presented",
    "ncbi_link": "GAS: "
  },
  {
    "caption": "ISRE-luciferase reporter assays in 293T cells stimulated with IFN-U co-transfected with BTV -VP6, -VP7, -NS1, -NS2, -NS3, or -NS4-expressing plasmids or empty expression plasmid (Control). Representative mean fold inductions of luciferase activity of three independent experiments are shown.",
    "ncbi_link": "ISRE: 
NS1: 
NS2: 
NS3: 
NS4: 
VP6: 
VP7: "
  },
  {
    "caption": "GAS-luciferase reporter assays in Vero cells stimulated with IFN-γ co-transfected with BTV -VP6, -VP7, -NS1, -NS2, -NS3, or -NS4-expressing plasmids or empty expression plasmid (Control). Representative mean fold inductions of luciferase activity of three independent experiments are shown.",
    "ncbi_link": "GAS: 
NS1: 
NS2: 
NS3: 
NS4: 
VP6: 
VP7: "
  },
  {
    "caption": "Immunoblot of 293T cells transfected with BTV -NS2, -NS3, -NS4 (FLAG) plasmids and NiV-V (HA) and WNV-NS5 (HA) used as control for STAT1 phosphorylation inhibition and DENV-NS5 (HA) used as control for STAT2 degradation.",
    "ncbi_link": "FLAG: 
HA: 
NS2: 
NS3: 
NS4: 
NS5: 
V: 920952"
  },
  {
    "caption": "Immunoprecipitation (IP) for STAT1/2 binding using 293T transfected with BTV -NS2, -NS3, or -NS4 plasmids. NiV-V used as positive control for STAT1 and STAT2 binding, DENV-NS5 used as positive control for STAT2 binding. Cells were treated (or left untreated) with 1000 U/ml universal-IFN for the final 16 h. Immunoblots of WCE and IP were probed (IB) for STAT1, STAT2, HA (NiV V, DENV NS5), FLAG (NS2, NS3, NS4) and GAPDH.",
    "ncbi_link": "NS2: 
NS3: 
NS4: 
NS5: 
V: 920952"
  },
  {
    "caption": "STAT1 phosphorylation and (G) STAT2 nuclear translocation in BTV-NS3-transfected Vero cells detected by immunofluorescence and confocal microscopy after 30 min IFN treatment. (Scale bar = 20 µm). Arrowheads in merge images indicate examples of transfected cells.",
    "ncbi_link": "NS3: "
  },
  {
    "caption": "Immunoblots of BTV-NS3-transfected 293T cells treated with proteasome inhibitors MG or LC. Membranes were probed for STAT1, STAT2, BTV-NS3 (FLAG) and GAPDH. (B-D) Immunoblots of BTV-NS3-transfected 293T cells treated with increasing concentration of lysosome acidification inhibitors (B) CQ or (C) NH4Cl or with increasing concentration of the (D) autophagosome formation inhibitor 3-MA, and probed (IB) for STAT1, STAT2, BTV-NS3 (FLAG) and GAPDH expression.",
    "ncbi_link": "NS3: "
  },
  {
    "caption": "293T cells were co-transfected with NS3 expression plasmid (or empty plasmid as control) and siRNA for Atg7 Lysates were obtained from FACS-sorted transfected cells. Immunoblots of sorted cells were probed for STAT1; STAT2; Atg7 FLAG-tagged NS3; LC3 and GAPDH.",
    "ncbi_link": "NS3: 
Atg7: 10533"
  },
  {
    "caption": "293T cells were co-transfected with NS3 expression plasmid (or empty plasmid as control) and siRNA for Beclin-1 (or siRNA control or no RNA as controls). Lysates were obtained from FACS-sorted transfected cells. Immunoblots of sorted cells were probed for STAT1; STAT2; Beclin-1 FLAG-tagged NS3; LC3 and GAPDH.",
    "ncbi_link": "NS3: 
Beclin-1: 8678"
  },
  {
    "caption": "Representative flow cytometry dot plots of Vero cells infected with rgBTV-8 or BTV-8 ΔNS3 and stained for BTV-VP7. Gating on VP7+ cells was used for sorting to obtain lysates from infected cells.",
    "ncbi_link": "NS3: "
  },
  {
    "caption": "Immunoblot of FACS-sorted Vero cells infected with rgBTV-8 or BTV-8 ΔNS3 and treated with IFN-U for 30min prior to fixation, staining and sorting. Membranes were probed for STAT1, P-STAT1, STAT2 and GAPDH.",
    "ncbi_link": "NS3: "
  },
  {
    "caption": "Immunofluorescence confocal images of Vero cells infected with rgBTV-8, BTV-8 ΔNS3 or mock-infected and treated with IFN-U for 30min prior to fixation and staining. Cells were stained for BTV-VP7 and (I) P-STAT1 or (J) STAT2. Nuclei were counterstained with DAPI. (Scale bar = 30 μm). (I) Arrowhead in merge image indicate partial inhibition of STAT1 phosphorylation in BTV-8 ΔNS3 infected cells. (J) Arrowhead in merge image shows STAT2 translocation to nucleus in BTV-8 ΔNS3-infected cells.",
    "ncbi_link": "NS3: "
  },
  {
    "caption": "WCE and FLAG-tag NS3 IP assay immunoblots of 293T transfected with BTV-NS3-FLAG plasmids and increasing amounts of Ubiquitin-HA plasmids, and probed (IB) for ubiquitin (HA), BTV-NS3 (FLAG) or GAPDH expression.",
    "ncbi_link": "FLAG: 
HA: 
NS3: 
Ubiquitin: "
  },
  {
    "caption": "Immunofluorescence staining of Vero cells co-transfected with BTV-NS3 and ubiquitin and acquired with Airyscan super-resolution. Scale bar = 10 μm. Inset shows detailed area and arrowheads indicate NS3 and ubiquitin signal co-incidence (scale bar = 2 μm).",
    "ncbi_link": "NS3: 
ubiquitin: "
  },
  {
    "caption": "FLAG-tag IP assay of BTV-NS3 and WCE immunoblot of 293T co-transfected with BTV FLAG-NS3-, -NS3-K13R, -NS3-K15R, -NS3-K13/15R or -NS3-PPRY/AARH plasmid and Ubiquitin-HA plasmid and probed (IB) for ubiquitin (HA), BTV-NS3 (FLAG), STAT2 and GAPDH expression.",
    "ncbi_link": "FLAG: 
HA: 
NS3: 
Ubiquitin: "
  },
  {
    "caption": "WCE and HA-tag Ubiquitin IP assay immunoblots of 293T transfected with Ubiquitin-HA plasmids and increasing amounts of BTV-FLAG-NS3-K13/15R, and probed (IB) for ubiquitin (HA), BTV-NS3-K13/15R (FLAG) or GAPDH expression.",
    "ncbi_link": "FLAG: 
HA: 
NS3: 
Ubiquitin: "
  },
  {
    "caption": "ISRE-driven luciferase reporter assay in 293T cells transfected with empty expression plasmid (Control), BTV -NS2 (300 ng), -NS3 (50, 300 and 600 ng), or -NS3-K13/15R (50, 300 and 600 ng)-expressing plasmids. Mean % inductions of luciferase activity of three independent experiments are shown.",
    "ncbi_link": "ISRE: 
NS2: 
NS3: "
  },
  {
    "caption": "FLAG-tag IP assay of BTV-NS3 and WCE immunoblot of 293T co-transfected FLAG-BTV-NS3 plasmid and HA-UB-WT or HA-UB lysine (K to R) mutants. IP were probed (IB) for ubiquitin (HA) and BTV-NS3 (FLAG) expression. WCE were probed for STAT1, STAT2, ubiquitin (HA), BTV-NS3 (FLAG), and GAPDH expression.",
    "ncbi_link": "FLAG: 
HA: 
NS3: 
UB: "
  },
  {
    "caption": "C Expression of F9 mRNA and protein in hepatic tissue of indicated mouse strains. Data represent means ± SE. M: Marker; arrowhead: FIX protein; Note: the bands of FIX in F9383STOP lanes are faint with small molecular weight smears.",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "F Measurement of blood loss over a 5-minute period after tail transection in mice at 8 weeks of age. Wild-type, n=5; F9Y381S, n=6; F9Y381D, n=13; F9383STOP, n=5.",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "G Survival rate of mice after the tail-clip challenge. The mice were monitored for two days after tail clipping. Wild-type, n=5; F9Y381S, n=6; F9Y381D, n=13; F9383STOP, n=5.",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "C Survival rate of mice after the tail-clip challenge. F9Y381D mice were treated with or without Cas9/sgRNA/donor DNA for 3 months. After tail-clip challenge, the survival rate of each group over 2 days was determined. Wild-type, n=9; untreated F9Y381D, n=13; DNA treated F9Y381D, n=14.",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "D Frequency of genetic modification in F9Y381D hepatocytes was determined either by deep sequencing (Cas9/donor vector treated group) or by TA-clone sequencing (Cas9/ssODN group).",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "G Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level was determined in F9Y381D mice 8 weeks after HTV injection (n=5).",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "E In vivo genome editing efficiency of whole liver tissues from mice treated with Adv(Cas9+G/T). (Left) HDR donor used for correction of Y381D mutation, and Illumina sequencing reads (rn) are presented. Red text indicates the correction of the F9 mutation, whereas blue text indicates the intended synonymous mutations. (Right) The percentage of indel or HDR corrections obtained through sequencing of 235 individual TA-clones (low dose) or Illumina sequencing (high dose) of treated mouseliver tissues.",
    "ncbi_link": "F9: 14071"
  },
  {
    "caption": "A: Upper panel: Strategy for the identification of oxidation resistant Ubc9 variants. Ubc9 was mutagenized by PCR under conditions that introduced 1 - 3 random mutations. Ubc9 variants were expressed in bacteria and the bacterial lysates of individual clones tested for E2 activity in the presence or absence of 1 mM H2O2. For this purpose, we used a FRET-based in vitro SUMOylation assay with recombinant SUMO E1, YFP-SUMO and CFP-RanGAPtail and ATP. Lower panel: Ubc9 W103R is H2O2 resistant. Bacterial lysates containing Ubc9 wt (left panel) or Ubc9 W103R (right panel) were tested as described.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: Ubc9 W103 mutants are H2O2 resistant but not fully active. Left panel: Recombinant Ubc9 W103R, W103A and W103F were purified (embedded panel). Resistance against oxidation was tested under conditions of limiting E1 enzyme: 21 nM Aos1/Uba2 and 73 nM Ubc9 were incubated with H2O2 prior to the addition of 160 nM each of YFP-SUMO1 and CFP-RanGAPtail. Right panel: To compare specific activities of wt and mutants in the absence of H2O2, sumoylation assays were carried out using limiting Ubc9 concentration. Reactions contained 35 nM Aos1/Uba2, 11 nM Ubc9, 85 nM each of YFP-SUMO1 and CFP-RanGAPtail and 1 mM ATP.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: In FRET-based assay, Ubc9 D100A is active upon H2O2 treatment. Ubc9 D100A was purified and compared for activity in the presence of H2O2 as described in Fig. 2B.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "C: Ubc9 wt and D100A are equally active in CFP-RanGAPtail SUMOylation. Assays were with 35 nM Aos1/Uba2 and 15 nM Ubc9.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "D: Ubc9 D100A is fully competent to form a thioester with SUMO. Single turnover reactions were performed using 630 nM E1, 3,3 µM SUMO1 and 600 nM Ubc9. Reactions were stopped at different time points by addition of non-reducing buffer..",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "E: Ubc9 wt and D100A are equally active in PIAS2b - dependent SUMOylation. Assays were with 300 nM GST-p53, 170 nM E1, 120 nM Ubc9, 5 µM SUMO2 and 49 nM GST-Pias2b",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "F: Ubc9 wt or D100A are equally active in RanBP2 - dependent SUMOylation. Assays were with 650 nM YFP-SP100, 110 nM of E1, 25 Ubc9, 40 nM RanBP2ΔFG and 3,5 µM SUMO1 (Left panel) or SUMO2 (Right panel).",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "A: Ubc9 D100A enzymatic activity can be recovered by limited amount of DTT. 21 nM Aos1/Uba2 and 75 nM Ubc9 were incubated with H2O2 for 30 min prior addition of 65 nM each YFP-SUMO1 and CFP-RanGAPtail diluted in DTT-free buffer. The final DTT concentration in the reaction was 6 µM. Prior to addition of ATP, extra amount of DTT was added at indicated final concentration.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: Both Uba2~Ubc9 disulfide formation and reduction are accelerated with Ubc9 D100A.100 nM E1 and 1 µM E2 were incubated in presence of 1 mM H2O2. One hour after H2O2 addition, 500 µM reduced glutathione was added. Samples were taken at indicated time points and the Uba2~Ubc9 disulfide was monitored by immunoblotting against Uba2. Lower panel: Quantification of the ratio between crosslinked Uba2 vs total Uba2",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "A: Generation of polyclonal populations of stable cells. Top panel: Replacement strategy: U2OS cells transfected with pIRES-hrGFP II-based vectors were selected via addition of G418. After 4 weeks, low level GFP expressing cells were sorted by FACS after 4 weeks and again after 8 weeks. Bottom panel: Stable cells express Ubc9 wt and D100A at levels comparable to endogenous Ubc9: U2OS or U2OS stable cells were transfected with siRNA targeting human Ubc9 mRNA for 72h or mocked transfected. Cells were lysed in Laemmli buffer and Ubc9 and a-tubulin as loading control were detected by immunoblotting.",
    "ncbi_link": "Ubc9: 7329
Ubc9: 22196"
  },
  {
    "caption": "B: Ubc9 D100A is severely impaired for disulfide bond formation with Uba2. Stable U2OS cells were transfected with siRNA against Ubc9 for 72h, treated with 250 µM H2O2 for different time points, from 2 min to 2 hours, lysed in non-reducing buffer and analyzed by immunoblotting against Ubc9 to detect the disulfide (upper panel) or free Uba2 as loading control (see also Appendix Fig. S5). Lower panel: relative intensities of Ubc9 bands were measured using imageJ. Highest intensities in both cell population were set to 1.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "C: Ubc9 D100A impairs cell survival upon H2O2 treatment. Ubc9 wt or Ubc9 D100A cells were transfected with siRNA against endogenous Ubc9 for 72h, transferred into 6 well plates (20 000 cells / well) and treated with increasing H2O2 concentration for 1h. Ten days later, cells were washed with PBS, fixed with 4% formaldehyde and stained with crystal violet. The area occupied by the cells was evaluated using ImageJ and the ColonyArea plugin. An arbitrary value of 1 was given to the area occupied by non-treated cells. The graph is showing the mean of 4 independent experiments. Error bars are S.E.M. *: p < 0.05",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "D: Constitutive expression of Ubc9 D100A affects cellgrowth. 103 cells were plated per 10 cm plate and cultivated for 10 days in 20% or 5% O2 incubators. Subsequently, cells were colored using crystal violet. The area of each clone was measured using ImageJ. Representative plates are shown in the upper panel. Lower left panel: Distribution of colony sizes, shown for one of the three biological replicates. Lower right panel: Comparison of the colonies size between \"Ubc9 wt\"and \"Ubc9 DA\" cells. The average size of \"Ubc9 wt\" was set to 1. Shown is the mean of 3 independent experiments, each of which was performed in technical triplicates. Error bars are S.E.M.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "A: Phosphorylation of ATM is impaired in Ubc9 D100A cells. Stable U2OS cell populations were depleted from endogenous Ubc9 by siRNA for 72 h before addition of 250 µM H2O2. At the indicated times, cells were lysed in Laemmli buffer and analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: Phosphorylation of gamma-H2AX is impaired in Ubc9 D100A. Experiment was performed as in A. Stable U2OS cell populations were depleted from endogenous Ubc9 by siRNA for 72 h before addition of 250 µM H2O2. At the indicated times, cells were lysed in Laemmli buffer and analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "C: Phosphorylation of Chk2 is impaired in Ubc9 D100A. Experiment was performed as described in A. Stable U2OS cell populations were depleted from endogenous Ubc9 by siRNA for 72 h before addition of 250 µM H2O2. At the indicated times, cells were lysed in Laemmli buffer and analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "D: Ubc9 D100A cells are fully competent for phosphorylation of ATM upon hydroxyurea exposure. Stable U2OS cell populations were exposed to 2.5 mM hydroxyurea or 250 µM H2O2. Cells were lysed at indicated time points and analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "E: Phosphorylation of Chk1 is not impaired in Ubc9 D100A cells. Stable U2OS cells were depleted from endogenous Ubc9 by siRNA for 72 h before addition of 2.5 mM hydroxyurea. At the indicated times, cells were lysed in Laemmli buffer and analysed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "A: Impaired y-H2AX and 53BP1 accumulation in Ubc9 D100A cells. Stable U2OS cells were transfected with siRNA against endogenous Ubc9 for 72 h. Cells were treated with 125 µM H2O2 and immunofluorescence microscopy was performed. Left panel: representative immunofluorescence images. Right panel: quantification of cells with γ-H2AX and 53BP1 foci. Error bars represent S.E.M, n=3 independent experiments * p < 0.05.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: H2O2 exposure leads to prolonged DNA damage in Ubc9 wt and Ubc9 D100A cells. Cells were treated as described in A. Stable U2OS cells were transfected with siRNA against endogenous Ubc9 for 72 h. Cells were treated with 125 µM H2O2 and immunofluorescence microscopy was performed. An alkaline comet assay was performed to evaluate the DNA damage. Representative images are shown. Error intervals represent S.E.M, n=4 independent experiments.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "A: Diamide is inducing the SUMO E1~E2 disulfide but not ATM phosphorylation. U2OS stable cell populations were depleted from endogenous Ubc9 by siRNA for 72 h before addition of 500 µM diamide or 500 µM H2O2. Cells were subsequently washed in PBS with 20 mM NEM and lysed in Laemmli buffer. The lysates were resolved by SDS-PAGE.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "B: Left panel: The PP2A inhibitor okadaic acid rescues the y-H2AX defect of the \"Ubc9 DA\" cells. \"Ubc9 wt\" or \"Ubc9 DA\" cells were treated with 0.25 µM okadaic acid for 30 min. After addition of 250 µM H2O2 in fresh medium for 3 hours, immunofluorescence microscopy was performed as described in Fig. 7A. Error bars represent S.E.M, n=3 independent experiments. Right panel: Representative immunofluorescence images.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "C: Left panel: Ubc9 D100A enhances sensitivity to Ara-C or etoposide. Cell survival assays were performed as described in Fig. 5C. Cells were exposed to Ara-C or etoposide (VP16) for 1 h and evaluated 10 days later. Right panel: N-acetylcysteine treatment rescues the higher toxicity of Ara-C or etoposide on \"Ubc9 DA\" cells. Cells were treated with 0.5 mM NAC 16 h prior to addition of etoposide or Ara-C. Graphs represent means of three to four independent experiments, error bars represent S.E.M. * p < 0.05.",
    "ncbi_link": "Ubc9: 22196"
  },
  {
    "caption": "(A) BI‐1 WT and KO MEFs cells were stably transduced with retroviruses expressing cytochrome b5-GFP to visualize the ER (green). Then cells were stained with lysotracker (red) and observed with a confocal microscope. Nucleus was stained with Hoechst (blue). Scale bar: 30 μm.",
    "ncbi_link": "cytochrome b5: 64835
BI‐1: 110213"
  },
  {
    "caption": "(B) BI‐1 WT and KO MEFs cells stimulated with EBSS for 3 h to induce autophagy. Acidic vesicles were visualized with a confocal microscope after lysotracker staining. Data represent the results of three independent experiments. Scale bar: 50 μm.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(C) (a) Epifluorescence imaging of BI‐1 KO cells stained with lysotracker; (b) electron micrograph of the same field of cells shown in (a); (c-e), magnification of lysotracker‐positive vesicles in BI‐1 KO cells exposed to EBSS for 3 h and visualized with a fluorescent microscope (c) and the same field subsequently imaged by EM (d). Overlapping images are presented (e). Left panel: analysis of vesicular structures by EM with morphologies resembling early (f), intermediate (g) and late (h) autophagy vesicles.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(D) Left panel: the distribution of endogenous LC3 was monitored by immunofluorescence and confocal microscopy in BI‐1 WT and KO MEFs cells at basal conditions (NT) or after exposure to EBSS for 3 h. Scale bar: left 15 μm and right 10 μm. Right panel: quantification of the number cells containing three or more LC3‐positive vesicles (N=160 cells). Mean and standard deviation are presented (N=4). Student's t‐test was used to analyse statistical significance, **P0.001 and *P0.01.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(E) BI‐1 WT and KO cells were transiently transfected with an expression vector for a monomeric‐tandem LC3-RFP-GFP construct. After 24 h, cells were exposed to EBSS for 3 h. Autophagy fluxes were monitored in living cells by visualizing the distribution of LC3‐positive dots in the red and green channels using a confocal microscope. Scale bar: 10 μm. Right panel: quantification of the ratio between red and yellow dots per cell is presented. Mean and standard error of the analysis of 15 cells are shown.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(A) BI‐1 WT and KO MEFs were treated with EBSS (left panel) or glucose/serum‐free RPMI media (right panel) for the indicated time points. Then, levels of LC3 were determined by western blot analysis. LC3‐I and LC3‐II forms are indicated. Hsp90 levels were assessed as loading control.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(F) BI‐1 KO cells were stably transduced with retroviruses expressing BI‐1-GFP or empty vector, and then levels of LC3‐II were assessed over time by western blot after exposure to EBSS. Right panel: as control, the levels of BI‐1-GFP were monitored by western blot. Hsp90 levels were used as loading control. In (B, D and E) mean and standard deviation are presented. Two‐way ANOVA was applied to analyse statistical significance. In parenthesis, the number of independent experiments for each time point is indicated. Student's t‐test was also used in (E) to analyse the statistical significance between each time point (*P0.001). In (B, D and E), normalization was performed as a ratio with the LC3‐II/Hsp90 normalized levels from non‐treated BI‐1 WT cells.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(A) Left panel: BI‐1 WT and KO MEFs cells were incubated in EBSS, and then cell viability was monitored using the MTS assay. Right panel: a similar experiment was performed after treating cells with the indicated concentration of tunicamycin for 24 h. Mean and standard deviation are presented of triplicates representative of three independent experiments.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(B) BI‐1 WT and KO cells were treated with three different starvation stimuli for 6 and 24 h. Cell death was determined after propidium iodide (PI) staining and FACS analysis. In addition, cells were treated with 100 ng/ml tunicamycin (Tm) for 24 h. Mean and standard deviation are presented of one experiment performed in triplicates.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(D) BI‐1 WT MEFs were stably transduced with lentiviral expression vectors to deliver an shRNA against bi‐1 mRNA or control mRNA (luciferase shRNA). Cell survival was measured after treatment of cells as described in (B). Mean and standard deviation of an experiment made by triplicate, representative of two independent experiments.",
    "ncbi_link": "luciferase: 
BI‐1: 110213
bi‐1: 110213"
  },
  {
    "caption": "(E) BI‐1 KO cells were stably transduced with retroviruses expressing BI‐1-GFP or empty vector, and then exposed to EBSS for indicated time points. Cell viability was monitored after PI staining by FACS. Mean and standard deviation are presented of triplicates representative of two independent experiments.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(A) BI‐1 WT and KO MEFs were treated with EBSS for 2 h, and the levels of phospho‐p70S6k were determined by western blot analysis. Total p70S6k is also shown.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(C) BI‐1 WT and KO cells were treated with EBSS for indicated time points, in the presence or absence of 10 μM of the JNK inhibitor SP600125. Levels of phosphorylation of JNK (pJNK) and LC3‐II were determined by western blot. The levels of total JNK and Hsp90 are shown as control (N=4). Image was assembled from cropped lanes of the same western blot analysis of the same gel.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(D) BI‐1 WT and KO cells were treated with EBSS for indicated time points in the presence or absence of 10 μM SP600125, and the electrophoretic shift associated with BCL‐2 phosphorylation was monitored by western blot.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(E) BI‐1 WT and KO cells were co‐transfected with expression vectors for Beclin‐1-MYC, BI‐1-HA, and BCL‐XL-FLAG. After 24 h, cells were treated with EBSS for 2 h or left untreated. The association of MYC‐tagged expressed Beclin‐1 and BCL‐XL-FLAG was assessed by immunoprecipitation of Beclin‐1 followed by western blot analysis.",
    "ncbi_link": "BCL‐XL: 12048
Beclin‐1: 56208
BI‐1: 110213"
  },
  {
    "caption": "(F) 293T cells were co‐transfected with expression vectors for Beclin‐1-MYC, BI‐1-HA, and BCL‐XL-FLAG. Cell extracts were prepared in CHAPS buffer and Beclin‐1-MYC immunoprecipitated, and the possible co‐precipitation of BI‐1-HA, and BCL‐XL-FLAG was assessed by western blot analysis (N=3). Asterisks indicate BI‐1 oligomers.",
    "ncbi_link": "BCL‐XL: 12048
Beclin‐1: 56208
BI‐1: 110213"
  },
  {
    "caption": "(G) (G) 293T cells were co‐transfected as described in (F) and BI‐1-HA was immunoprecipitated, and the possible co‐precipitation of Beclin‐1-MYC, and BCL‐XL-FLAG determined by western blot analysis (N=3). Figure source data can be found with the Supplementary Information.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(A) BI‐1 KO MEFs were stably transduced with lentiviral vectors expressing an shRNA against beclin‐1 (shBeclin‐1) or ire1α (shIRE1α) mRNA or luciferase (shLuc) as control. The levels of LC3, Beclin‐1, IRE1α and Hsp90 were monitored by western blot.",
    "ncbi_link": "luciferase: 
beclin‐1: 56208
ire1α: 78943
BI‐1: 110213"
  },
  {
    "caption": "(B) BI‐1 KO MEFs were stably transduced with lentiviral vectors as described in A. Cells were exposed to EBSS for 3 h, and then LC3 levels were analysed by western blot. Image was assembled from cropped lanes of the same western blot analysis.",
    "ncbi_link": "BI‐1: 110213"
  },
  {
    "caption": "(C) Endogenous LC3 distribution was visualized using immunofluorescence and confocal microscopy in BI‐1 KO/shLuc and BI‐1 KO/shBeclin‐1 cells. Quantification represents the visualization of at least 180 cells. Student's t‐test was used to analyse statistical significance. Mean and standard deviation are presented, *P0.001, NS: non‐significant.",
    "ncbi_link": "Beclin‐1: 56208
BI‐1: 110213"
  },
  {
    "caption": "(D) LC3 was visualized and quantified in BI‐1 KO/shLuc and BI‐1 KO/shIRE1α cells described in (B) by immunofluorescence and confocal microscopy analysis.",
    "ncbi_link": "IRE1α: 78943
BI‐1: 110213"
  },
  {
    "caption": "(E) BI‐1 KO cells were transiently transfected with a TRAF2 dominant‐negative (TRAF2‐DN) construct or empty vector (mock), and after 48 h cells were stimulated with EBSS and the levels of LC3‐II and Hsp90 were monitored by western blot. Right panel: quantification of relative LC3‐II levels normalized with Hsp90 and non‐treated cells. Mean and standard deviation are presented.",
    "ncbi_link": "BI‐1: 110213
TRAF2: 22030"
  },
  {
    "caption": "(F) 293T cells were co‐transfected with expression vectors for HA‐tagged IRE1α (IRE1-HA), TRAF2-FLAG, and MYC‐tagged BI‐1 (BI1-MYC). After 48 h of transfection, HA‐tagged proteins were immunoprecipitated and the possible interaction with TRAF2 was analysed by western blot. Right panel: the percentage of TRAF2 dissociation from IRE1α by the presence or absence of BI‐1 was quantified and normalized with the expression levels observed in the inputs. For comparison, the co‐IP signal observed in the absence of BI‐1 was normalized as 100% co‐IP in each independent experiment (N=3). Mean and standard deviation are presented, *P0.05. Figure source data can be found with the Supplementary Information.",
    "ncbi_link": "IRE1: 78943
IRE1α: 78943
BI‐1: 110213
BI1: 110213
TRAF2: 22030"
  },
  {
    "caption": "(A) The expression of dBI‐1 was knocked down in Drosophila melanogaster. Then, relative expression levels of dBI‐1 mRNA were monitored by semiquantitative PCR. Actin levels were monitored as control.",
    "ncbi_link": "Actin: 
dBI‐1: 38936"
  },
  {
    "caption": "(B) (B) LC3 levels were monitored in control (Da‐Gal4>huLC3:GFP) or dBI‐1 RNAi larvae (Da‐Gal4>huLC3:GFP, Dcr2, dBI‐1i) under basal or fasting conditions. Then, huLC3-GFP levels were analysed by western blot. In addition, dBI‐1i larvae were treated with 100 μM SP600125 (added in the growing media).",
    "ncbi_link": "Gal4: 
dBI‐1: 38936
Dcr2: 36993
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) Left panel: the presence of LC3‐positive vesicles (white arrowheads) was monitored by confocal microscopy in control (Da‐Gal4>huLC3>GFP) and dBI‐1 knockdown pupae (Da‐Gal4>huLC3:GFP, Dcr2, dBI‐1i) after 6 h of puparium formation. The organization of actin cytoskeleton was monitored by staining with phalloidin (Ph, red). Nucleus was stained with Topro (blue). Scale bar: left 20 μm and right 11 μm. Right panel: overexpression of dBI‐1 (dBI‐1EY03662) delays salivary gland degradation. Overexpression of dBI‐1 was confirmed by semiquantitative RT-PCR. Actin levels were monitored as loading control. Right panel: wild‐type control and dBI‐1EY03662 pupae were analysed at 14 h after puparium formation. Superficial and internal confocal planes of the cells are presented. Scale bar: 40 μm.",
    "ncbi_link": "Actin: 
Gal4: 
dBI‐1: 38936
Dcr2: 36993
LC3: 440738///81631///84557"
  },
  {
    "caption": "(D) Wild‐type control and dBI‐1EY03662 larvae were cultured in fasting conditions for different periods of time and fat body stained with lysotracker (red) and Hoechst (blue). Then, lysosomal content in the fat body was visualized by epifluorescence microscopy. The percentage of cells presenting lysotracker‐positive stain is indicated. Scale bar: 50 μm.",
    "ncbi_link": "dBI‐1: 38936"
  },
  {
    "caption": "(E) Control or dBI‐1 knockdown adult flies were exposed to nutrient starvation and then animal viability was monitored over time for several days. In all, 100 individuals were monitored in each condition. Data represent mean and standard error (N=3). Two‐way ANOVA was used to analyse statistical significance between groups.",
    "ncbi_link": "dBI‐1: 38936"
  },
  {
    "caption": "(F) Second instar dBI‐1 RNAi or control larvae were grown in food supplemented with 25 μg/ml Tm dissolved in DMSO or 0.5% DMSO as control. The number of individual reaching the adult fly stage was evaluated. Mean and standard error are presented (N=3), **P0.01.",
    "ncbi_link": "dBI‐1: 38936"
  },
  {
    "caption": "(A) The levels of LC3, Atg5/Atg12 complex, Beclin‐1, Bcl‐2, Bcl‐XL, IRE1α and Hsp90 were monitored in liver protein extracts of bi‐1+/+ and bi‐1−/− at 6‐month‐old mice. Each well represents independent mice.",
    "ncbi_link": "bi‐1: 110213"
  },
  {
    "caption": "(C) bi‐1+/+ and bi‐1−/− mice were injected with 50 ng/ml of tunicamycin by intraperitoneal injection (N=3) and then LC3 levels were monitored in liver protein extracts by western blot analysis. Right panel: quantification of relative LC3‐II levels, **P0.005.",
    "ncbi_link": "bi‐1: 110213"
  },
  {
    "caption": "B) Segmentation of a prepupa wing imaginal disc epithelium where myosin II levels have been reduced",
    "ncbi_link": "myosin II: 38001"
  },
  {
    "caption": "A/B Lysates from parental, SMCR8 KO (A) or C9orf72 KO (B) 293T cells were analyzed by immunoblotting. * indicates unspecific protein band detected by C9orf72 antibody. Calnexin served as loading control.",
    "ncbi_link": "C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "C Rescue of C9orf72 protein levels in SMCR8 KO cells after transient overexpression of untagged- or C-terminal tagged SMCR8 analyzed by immunoblotting. * indicates unspecific protein band detected by C9orf72 antibody. Calnexin served as loading control.",
    "ncbi_link": "SMCR8: 140775"
  },
  {
    "caption": "G Parental and SMCR8 KO cells were subjected to a cycloheximide (CHX) chase in the absence or presence of DMSO or Btz. * indicates unspecific protein band detected by C9orf72 antibody. α‑tubulin served as loading control. NRF2 confirmed proteasomal inhibition by Btz.",
    "ncbi_link": "SMCR8: 140775"
  },
  {
    "caption": "C SMCR8 KO cells were treated with DMSO or MLN7243 prior to fixation and immunostaining with an anti-C9orf72 antibody. Untreated parental and C9orf72 KO cells served as controls. Scale bar, 10 µm.",
    "ncbi_link": "C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "D Empty or stably C9orf72-HA expressing SMCR8 KO cells were treated with Btz or DMSO followed by lysis and immunoblotting. Untreated parental cells served as control. Calnexin served as loading control. NRF2 confirmed proteasomal inhibition by Btz.",
    "ncbi_link": "HA: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "E Parental and SMCR8 KO cells stably expressing C9orf72-HA were subjected to CHX chase in absence and presence of DMSO or Btz. NRF2 confirmed proteasomal inhibition by Btz.",
    "ncbi_link": "HA: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "F Lysates from empty or stably C9orf72-HA expressing SMCR8 KO cells treated with DMSO or Btz were subjected to HA-IP under denaturing conditions in the absence and presence of the catalytic domain of the deubiquitinase USP2.",
    "ncbi_link": "HA: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "D Lysates from C9orf72-HA expressing parental and SMCR8 KO cells treated with DMSO or Btz were subjected to HA-IP followed by immunoblot analysis. Empty parental and SMCR8 KO served as controls. : NRF2 confirmed proteasomal inhibition by Btz.",
    "ncbi_link": "HA: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "E SMCR8 KO cells expressing C9orf72-HA were transiently transfected with GFP-UBR5 or GFP and treated with DMSO or Btz. Lysates were incubated with Streptavidin agarose coupled to biotinylated GFP VHH nanobodies and bound proteins were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
HA: 
C9orf72: 203228
SMCR8: 140775
UBR5: 51366"
  },
  {
    "caption": "A SMCR8 KO cells stably overexpressing C9orf72-HA were treated with Btz and lysates were subjected to HA-IP under mild conditions in the absence and presence of the catalytic domain of the deubiquitinase USP2. FK2 confirmed deubiquitination by USP2.",
    "ncbi_link": "HA: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "D SMCR8 KO cells transiently overexpressing GFP, GFP-C9orf72 WT or GFP-C9orf72 mutant K156R, K388R, K414R, K422R, K424R, K425R, K428R (KR7) were treated with Btz followed by streptavidin pulldown with biotinylated GFP VHH nanobodies under denaturing conditions.",
    "ncbi_link": "GFP: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "B SMCR8 KO cells stably expressing GFP-C9orf72 were treated with DMSO or Btz followed by denaturing lysis and differential USP2 treatment. Lysates were incubated with biotinylated GFP VHH nanobodies coupled to Streptavidin agarose and enriched proteins were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
C9orf72: 203228
SMCR8: 140775"
  },
  {
    "caption": "D SMCR8 KO cells were transiently transfected with siUBR4/5, siCTRL or left untreated but grown in the presence of Btz. Lysates were subjected to immunoblotting. Quantification of C9orf72 levels in SMCR8 KO cells treated with siUBR4/5 or siCTRL. n = 3 biological replicates. Data represent mean ± SD. Statistical analysis of C9orf72/α‑tubulin ratio was performed using one-tailed, unpaired Student's t-test. * p < 0.05. Representative Western blot is shown beside. α‑tubulin served as loading control.",
    "ncbi_link": "SMCR8: 140775
UBR4: 23352"
  },
  {
    "caption": "(b) siRNA-mediated depletion of p62 from U2OS cells results in moderate MR accumulation, compared with a control depletion (lamin A/C). For quantification, MRs were counted in control cells and in p62-depleted cells that were negative for p62 staining. Data are means ± s.d. of three independent experiments (n, total number of cells counted; P, probability of a two-tailed paired t-test).",
    "ncbi_link": "lamin A/C: 4000
p62: 8878"
  },
  {
    "caption": "(a) Atg8 (LC3) localizes to the MR during abscission. The upper panels show stills from time-lapse microscopy of GFP-Atg8-expressing cells. The arrowhead points to the accumulation of Atg8 at the site of the MR during abscission. The enlarged clipping on the right shows the midbody area at time-point 68 min. Scale bar is 10 μm.",
    "ncbi_link": "Atg8: 84557"
  },
  {
    "caption": "(b) Cytosolic MRs are found inside Atg8-positive vesicles. U2OS cells stably expressing GFP-Atg8 were fixed and stained for MKLP1 (red) and α-tubulin (blue). Scale bars are 10 μm and 1 μm for the enlarged boxed areas. Putative different stages of autophagosomes (left) and lysosomes (right) are shown.",
    "ncbi_link": "Atg8: 84557"
  },
  {
    "caption": "(b) siRNA-mediated depletion of Atg6 (Beclin-1) and Atg7 from HeLa cells causes MR accumulations. The right panel shows the quantification of MRs per cell (mean ± s.d. of three independent experiments); the left panel the efficiency of Atg6 and Atg7 depletion.",
    "ncbi_link": "Atg7: 10533
Atg6: 8678
Beclin-1: 8678"
  },
  {
    "caption": "(A) RT-qPCR analyses of Hlf, Tef, Dbp and Nfil3 expression monitoring changes induced by acute ERS in MPH (3 to 5 independent experiments) (left panel) or mouse liver (5 mice per group) (right panel). The bar graphs show means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05.",
    "ncbi_link": "Dbp: 13170
Hlf: 217082
Nfil3: 18030
Tef: 21685"
  },
  {
    "caption": "(D) Enrichment scores from GSEA performed using LIVER-ID genes repressed by acute ERS in MPH (MPH ERS DOWN) as the gene set and liver transcriptomic changes induced by acute ERS and/or deletion of Nfil3 (NFIL3 KO) as the ranked gene lists were integrated and corrected for multiple testing using the BubbleGUM tool. For the NFIL3 KO ERS vs WT ERS comparison, the Core Enrichment genes (i.e. the subset of genes that contributes most to the enrichment result) were subjected to functional enrichment analyses using the ToppGene Suite. The top ranked KEGG Pathway with its Bonferroni-corrected p-value is shown.",
    "ncbi_link": "Nfil3: 18030
NFIL3: 18030"
  },
  {
    "caption": "(F) The Integrated Genome Browser (IGB) was used to visualize ChIP-seq profiles for NFIL3 (green) and several LIVER-ID TFs (red) in the mouse liver at the Gsta3 gene locus. Levels of H3K27ac in MPH and cells from the non-parenchymal fraction (NPC) are shown in blue. The grey bar indicates the position of a BRD4 SE.",
    "ncbi_link": "BRD4: 57261
Gsta3: 14859
NFIL3: 18030"
  },
  {
    "caption": "(B) Left panel, BRD4 mRNA (4 independent experiments) or protein expression levels (5 independent experiments; densitometric quantification in MPH subjected to acute ERS. The bar graphs show means ± SD (standard deviations). Student's t-test was used to assess statistical significance. Right panel, Total protein extracts from MPH pre-treated for 3h with 0.01µM MZ1 followed by addition of 1µM thapsigargin (ERS) for 4h were subjected to Western blot with an antibody against BRD4. LMNA was used as loading control.",
    "ncbi_link": "BRD4: 57261"
  },
  {
    "caption": "(D) Heatmaps showing average H3K27ac ChIP-seq signals in MPH at LIVER-ID domains overlapping (+) or not (-) with BRD4 SE. The arrow indicates the position of gene transcriptional start sites.",
    "ncbi_link": "BRD4: 57261"
  },
  {
    "caption": "(E) Box plots showing Log2 FC ERS/Control in MPH (3 independent experiments) (left panel) or mouse liver (3 mice per group) (right panel) for genes associated with LIVER-ID + BRD4 SE or LIVER-ID - BRD4 SE Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. Student's t-test was used to assess statistical significance, *P < 0.05.",
    "ncbi_link": "BRD4: 57261"
  },
  {
    "caption": "(B) RT-qPCR analyses of Hnf4a, Nr1h4 and Foxa2 expression in MPH treated with vehicle (Control) or 1µM thapsigargin (ERS) for 1h or 4h (4 independent experiments). The bar graph shows means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05.",
    "ncbi_link": "Foxa2: 15376
Hnf4a: 15378
Nr1h4: 20186"
  },
  {
    "caption": "(B) Box plots showing Log2 FC ERS/Control in mouse liver for ERS UP genes 8h and 34h after tunicamycin injection in WT or ATF6 KO mice (3 mice per experimental condition). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05. NS, not significant. (C) Similar analyses to panel (B) for ERS DOWN and LIVER-ID genes (3 mice per experimental condition). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05. ",
    "ncbi_link": "ATF6: 226641"
  },
  {
    "caption": "(D) Main observations from (Huck et al., 2019) (left) and box plots showing Log2 FC HNF4A KO/Control in mouse liver (3 mice per group) for LIVER-ID genes and TFs 5 days after PHx (right). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC HNF4A KO/Control is statistically different from 0, *P < 0.05.",
    "ncbi_link": "HNF4A: 15378"
  },
  {
    "caption": "F - Left: relative mRNA expression of Chat in ChATfl/fl and ChATfl/fl;Vav-iCre IWAT (n = 9). Chat expression was analyzed by qPCR and normalized to levels of Tbp using the 2-ΔΔCt method. Right: quantification by LC/MS-MS of Ach concentration in SVF isolated from ChATfl/fl and ChATfl/fl;Vav-iCre IWAT (n = 6).",
    "ncbi_link": "Chat: 12647
ChAT: 12647
iCre: 2777477
Tbp: 21374
Vav: 22324"
  },
  {
    "caption": "Body weight (C) of ChATfl/fl;LysM-Cre (n = 7 for ChATfl/fl, n = 8 for Cre ChATfl/fl;Cd4-Cre (n = 6 for ChATfl/fl and n = 7 for Cre ChATfl/fl;Mb1-Cre (n = 12 in C, n = 9 for ChATfl/fl, n = 8 for Cre and littermate ChATfl/fl mice housed at RT.",
    "ncbi_link": "Cd4: 12504
Mb1: 12518
ChAT: 12647
Cre: 2777477
LysM: 17105"
  },
  {
    "caption": "E-G - mRNA expression of Chrna2 and thermogenic genes in IWAT of ChATfl/fl;LysM-Cre (n = 24 for ChATfl/fl_RT, n = 25 for Cre_RT, n = 20 for ChATfl/fl_CE, n = 20 for Cre_CE) (E), ChATfl/fl;Cd4-Cre (n = 17 for ChATfl/fl_RT, n = 22-23 for Cre_RT, n = 19 for ChATfl/fl_CE, n = 22 for Cre_CE) (F), ChATfl/fl;Mb1-Cre (n = 10 for ChATfl/fl_RT, n = 11 for Cre_RT, n = 9-12 for ChATfl/fl_CE, n = 13 for Cre_CE) (G) and littermate ChATfl/fl mice housed at RT or 4oC (CE) for 6 h. An insert graph in (E) highlights mRNA expression of Chrna2 and thermogenic genes in IWAT of ChATfl/fl and ChATfl/fl;LysM-Cre mice after 6 h CE.",
    "ncbi_link": "Cd4: 12504
Mb1: 12518
ChAT: 12647
Chrna2: 110902
Cre: 2777477
LysM: 17105"
  },
  {
    "caption": "K - Average whole-body oxygen consumption rate (OCR) of ChATfl/fl (n = 10) and ChATfl/fl;LysM-Cre (n = 14) mice housed in metabolic chambers at RT or CE for 6 h (from 9 a.m. to 3 p.m.).",
    "ncbi_link": "ChAT: 12647
Cre: 2777477
LysM: 17105"
  },
  {
    "caption": "J - Relative mRNA expression of Adrb1, Adrb2 and Adrb3 in IWAT MΦ sorted from WT mice (n = 4). Expression was measured by qPCR and normalized to levels of Tbp using the 2-ΔΔCt method.",
    "ncbi_link": "Adrb1: 11554
Adrb2: 11555
Adrb3: 11556
Tbp: 21374"
  },
  {
    "caption": "F - LC/MS-MS quantification of acetylcholine levels secreted by SVF cells derived from IWAT of β2WT and β2KO mice treated with veh or 1 mg/kg Form for 2 h (n = 3).",
    "ncbi_link": "β2: 11555"
  },
  {
    "caption": "M - Left: BMDMs were treated for 2 h with veh or pan β-AR agonist (100 μM NE), β2-AR antagonist (5 μM butoxamine, Buto) or a combination of NE and β2 antagonist (Buto) (n = 6). Chat mRNA expression was measured by qPCR and normalized to levels of Tbp using the 2-ΔΔCt method. Right: Total number of ChAT-eGFP+ BMDMs. ChAT-eGFP BMDMs were treated for 2 h with veh or pan β-AR agonist (100 μM NE), β2-AR antagonist (5 μM butoxamine, Buto) or a combination of NE and β2-AR antagonist (Buto) (n = 4). An equal number of events (50,000) were analyzed by flow cytometry.",
    "ncbi_link": "Chat: 12647
Tbp: 21374"
  },
  {
    "caption": "N - Left: Bicompartmental co-culture system with media alone (Ctrl) or WT SVF cells isolated from IWAT in the upper compartment (transwell insert) and freshly isolated IWAT explants from β-less mice in the lower compartment. Cells were co-cultured for 4 h in the presence or absence of β2-AR agonist (2.5 μM Form). 150 μM rivastigmine was added to the media to prevent degradation of Ach. Right: qPCR analyses of Chat and Ucp1 mRNA levels in β‑less explants following co-culture with media (n = 4), vehicle (n = 10) or β2-AR agonist (n = 10) treated SVF cells. mRNA expression was measured by qPCR and normalized to levels of Tbp using the 2-ΔΔCt method.",
    "ncbi_link": "Chat: 12647
Tbp: 21374
Ucp1: 22227"
  },
  {
    "caption": " C Relative mRNA expression of Apopt1 normalized to the expression of GAPDH in skeletal muscle and liver of wild-type, heterozygous and knock-out mice of three months of age. Data are presented as mean ± SEM (n = 6 mice per genotype). The asterisks represent the significance levels calculated by two-way ANOVA with Sidak's multiple comparisons test: Muscle - ***P = 0.0001 (WT vs KO), *P = 0.0310 (WT vs het), *P = 0.0395 (het vs KO), Liver - **P = 0.0022 (WT vs KO), *P = 0.0101 (WT vs het) ",
    "ncbi_link": "Apopt1: 68020"
  },
  {
    "caption": " A APOPT1HA was expressed in S6 and S2 immortalized fibroblasts as shown by the Western blot immunovisualization. The expression levels were tested at different days after transduction. The graph on the right shows the activities of CIV normalized to CS in three biological replicates per cell line. Data are presented as mean ± SEM (n = 3). The asterisks represent the significance levels calculated by two-way ANOVA with Tukey's multiple comparisons test: **P = 0.0030 (S6 naïve vs S6 APOPT1HA), *P = 0.0165 (S6 EV vs S6 APOPT1HA )",
    "ncbi_link": "APOPT1: 84334"
  },
  {
    "caption": " B APOPT1 GFP was expressed in S6 and S2 immortalized fibroblasts as shown by the Western blot immunovisualization. The graph on the right shows the activities of CIV normalized to CS in four biological replicates per cell line. Data are presented as mean ± SEM (n = 4). The asterisks represent the significance levels calculated by two-way ANOVA with Tukey's multiple comparisons test: **P = 0.0066 (S6 naïve vs S6 APOPT1GFP), ***P = 0.0006 (S6 EV vs S6 APOPT1GFP), *P = 0.0169 (S2 naïve vs S2 APOPT1GFP), ***P = 0.0008 (S2 EV vs S2 APOPT1GFP)",
    "ncbi_link": "APOPT1: 84334"
  },
  {
    "caption": " E L-[35S]-Methionine pulse-chase labeling of mtDNA-encoded proteins. After a two-hour exposure with the radioactive label (pulse), cells were cultured in cold medium for the indicated chase times. The graphs show the densitometric quantification of the bands corresponding to MT-CO1 (left graph) and MT-CO2+MT-CO3 (right graph) normalized to the ATP6 band over the indicated time points. Graphs represent the values of three biological replicas for each cell line. Data are presented as mean ± SEM (n = 4 for controls, n = 2 for S2/S6/S2 APOPT1GFP/S6 APOPT1GFP). The asterisks represent the significance levels calculated by two-way ANOVA with Tukey's multiple comparisons test: MT-CO1 - **P = 0.0039 ( 3.5 hours, controls vs S6), *P = 0.0202 (3.5 hours, controls vs S2), *P = 0.0163 (5 hours, S6vs S6 APOPT1GFP), *P = 0.0118 (5 hours, controls vs S2), **P = 0.0011 (20 hours, controls vs S6), *P = 0.0343 (20 hours, S2 vs S2 APOPT1GFP), ***P = 0.0007 (20 hours, S6 vs S6 APOPT1GFP ), ***P = 0.0002 (20 hours, controls vs S2), *****P < 0.0001 (20 hours, controls vs S6), MT-CO2/MT-CO3 - *P = 0.0194 (3.5 hours, S6 vs S6 APOPTGFP), ***P = 0.0003 (3.5 hours, controls vs S6), *P = 0.0375 (5 hours, S6 vs S6 APOPT1GFP), *P = 0.0234 (20 hours, S2 vs S2 APOPT1GFP), ****P < 0.0001 (20 hours, S6 vs S6 APOPT1GFP), **P = 0.0013 (20 hours, controls vs S2), ****P < 0.0001 (20 hours, controls vs S6)",
    "ncbi_link": "APOPT: 84334
APOPT1: 84334"
  },
  {
    "caption": " C Western blot analysis of SDS-PAGE of total lysates from 143B cells overexpressing tagged APOPT1 (as indicated) and exposed to 100 µM H2O2, as illustrated by the scheme (H2O2 treatment), for the indicated times. The graphs represent the densitometric quantification of the tagged APOPT1 signal at each time point. The graph inset shows that the increase of APOPT1 occurs in the first minutes after the exposure to H2O2 ",
    "ncbi_link": "APOPT1: 84334"
  },
  {
    "caption": " D Western blot analysis of SDS-PAGE of total lysates from 143B cells overexpressing tagged APOPT1 (as indicated) and exposed to 5 µM MitoParaquat (MitoPQ), as illustrated by the scheme (MitoPQ treatment), for the indicated times. The graphs represent the densitometric quantification of the tagged APOPT1 signal at each time point. The graph inset shows that the increase of APOPT1 occurs in the first minutes after the exposure to MitoPQ ",
    "ncbi_link": "APOPT1: 84334"
  },
  {
    "caption": " A Western blot analysis of SDS-PAGE of different mitochondrial proteins in total lysates from the indicated cell lines treated with 5 µM MitoPQ at the indicated times. UT: untreated cells. B Densitometric quantification of APOPT1GFP signal during the treatment in two biological replicas. C Densitometric quantification of MT-CO1 signal in the non-complemented APOPT1-less cells (S6 GFP) vs. the complemented cells (S6 APOPT1GFP). Three biological replicas (n=3) were carried out for each cell line. The signals in UT S6 APOPT1 were considered 100%. The levels of MT-CO1 were significantly lower in the S6 GFP patient cells after 20 hours of MitoPQ treatment compared to the untreated cells (*P = 0.0202, two-tailed unpaired Student's t-test). D Densitometric quantification of MT-CO2 signal in the non-complemented APOPT1-less cells (S6 GFP) vs. the complemented cells (S6 APOPT1GFP). Three biological replicas were carried out for each cell line. The signals in UT S6 APOPT1 were considered 100% ",
    "ncbi_link": "APOPT1: 84334"
  },
  {
    "caption": "C Co-IP with  HEK293T cells co-transfected with plasmids encoding   Hwa-Flag and ZNRF3-HA or ZNRF3ΔRING. Lysates  immunoprecipitated with anti-Flag were immunoblotted with HA  and Flag antibodies. Blots are representative of 3 independent experiments. D Co-IP  with HEK293T  cells co-transfected with plasmids encoding Hwa-Flag and ZNRF3-HA or ZNRF3ΔRING. Lysates  immunoprecipitated  with anti-HA were immunoblotted with  Flag and HA antibodies. Blots are representative of 3 independent experiments. ",
    "ncbi_link": "Flag: 
HA: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "E Colocalization of Hwa-Flag (red) and  ZNRF3-HA (green) or ZNRF3ΔRING-HA (green) in Hela cells is indicated by yellow dots. Baf-A1, 50 nM, 12 hrs. Magnification: 100 ×; scale bar: 10 μm.",
    "ncbi_link": "HA: 
ZNRF3: 108717096"
  },
  {
    "caption": "B Whole mount  in situ hybridization of Spemann organizer markers  chrd, gsc, and xnr3 in gastrula embryos (stage 10.5). Oocytes were injected with AS or mRNAs as indicated, Dosage: znrf3 AS (3 ng AS4 + 3 ng AS9), znrf3  mRNA 100 pg, znrf3ΔRING mRNA 50 pg. embryos were obtained through Host transfer technology. Scale bars: 1 mm.",
    "ncbi_link": "chrd: 108716188///108716939///398045
gsc: 397748///397752
xnr3: 373597///378537
znrf3: 108717096"
  },
  {
    "caption": "H Whole mount in situ hybridization of Spemann organizer markers chrd and gsc in  gastrula embryos (stage 10.5). Embryos were injected and obtained as descripted in (G). Scale bars: 1 mm.",
    "ncbi_link": "chrd: 108716188///108716939///398045
gsc: 397748///397752"
  },
  {
    "caption": "I Representative phenotypes  of  tailbud stage Xenopus leavis embryos injected with 500 pg mRNAs of ctrl (gfp mRNA), znrf3FL, and znrf3 truncations as indicated at 4-cell stage. Duplicated axes (red arrowhead). znrf3FL, full-length znrf3; znrf3ΔRING, znrf3 lacking the RING domain; znrf31-320, amino acids  1-320 of  znrf3; znrf3320-606, amino acids 320-606 of znrf3; znrf3606-854, amino acids 606-854 of znrf3. Scale bars: 1 mm.",
    "ncbi_link": "gfp: 
znrf3: 108717096"
  },
  {
    "caption": "B Hwa ubiquitination was analyzed under denaturing conditions. HEK293T cells co-transfected with wildtype His-HA-Ubiquitin (His-HA-Ub WT) or lysine-less mutant (K0), Hwa-Flag, and  ZNRF3-Myc. The lysates were immunoblotted with Myc,  Flag, and α-tub (α-tubulin). Lysates immunoprecipitated  with anti-Flag were immunoblotted  with HA and Flag  antibodies. K0, all lysine sites on ubiquitin were mutated. Blots  are representative of 3 independent experiments.",
    "ncbi_link": "Flag: 
HA: 
His: 
Myc: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "D Screen of ZNRF3-mediated Hwa ubiquitination  sites under denaturing conditions. HEK293T cells were co-transfected with His-HA-Ub, Hwa-Flag or  Hwa10KR-Flag, and  ZNRF3 or ZNRF3ΔRING. The lysate was  immunoblotted  with Myc, Flag, and α-tub (α-tubulin). Lysates immunoprecipitated with anti-Flag were  immunoblotted  with HA and Flag antibodies. Hwa10KR-Flag mutant, all lysine sites in Hwa  sequence were replaced with arginine. Denaturing conditions: before  immunoprecipitation, lysates were denatured by adding SDS to a final concentration at 1% and boiling at 95℃ for 15 min. Blots  are representative of 3 independent experiments.",
    "ncbi_link": "Flag: 
HA: 
His: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "A Western blot  analysis of Hwa in HEK293T cells co-transfected with Hwa-Flag, and ZNRF3-HA   (5 μg) or ZNRF3ΔRING (2.5 μg). Lysate was immunoblotted with  Flag, HA, and GAPDH  antibodies.  Blots  are representative of 3 independent experiments. B Densitometry analysis of Hwa  bands from the western blot in (A) for corresponding lanes normalized to GAPDH. n = 3 independent experiments, mean ± SEM, ns p > 0.05, **p < 0.01 by unpaired t test. ",
    "ncbi_link": "Flag: 
HA: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "C Western blot analysis of Hwa in HEK293T cells co-transfected with Hwa-Flag and ZNRF3-HA. Cells were treated with or without Baf-A1 (50 nM) or MG132 (20 μM) for about 12 hours. Lysates were immunoblotted with  Flag, HA, and  α-tub (α-tubulin) antibodies.  Blots are representative of 3 independent experiments. D Densitometry analysis of Hwa bands from the western blot in (C) for corresponding lanes normalized to α-tubulin. n = 3 independent experiments, mean ± SEM, ns p > 0.05, **p < 0.01, ****p < 0.0001 by unpaired t test. ",
    "ncbi_link": "Flag: 
HA: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "F Colocalization by immunofluorescence of  Hwa (green signals) with  lysosome (LAMP1, red signals) in Hela  cells. Cells were co-transfected with Hwa-Flag, and  ZNRF3-HA  or ZNRF3ΔRING-HA. Magnification, 100 ×; scale bars: 10 μm.",
    "ncbi_link": "Flag: 
HA: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "I Surface biotinylation and streptavidin pulldown  of Hwa-Myc-Flag. HEK293T cells were co-transfected with Hwa-MF (Hwa-Myc-Flag), and ZNRF3-Myc or  ZNRF3ΔRING-Myc. Lysate was immunoblotted  with Myc, Flag, and GAPDH  antibodies. Lysates immunoprecipitated  with anti-Flag (2nd elution) were immunoblotted with Flag and HA  antibodies.",
    "ncbi_link": "Flag: 
Myc: 
Hwa: 108718903
ZNRF3: 108717096"
  },
  {
    "caption": "C Whole mount in situ hybridization of Spemann organizer markers chrd  and gsc in gastrula embryos. Embryos  were obtained as descripted in (B). Scale bars: 1mm.",
    "ncbi_link": "chrd: 108716188///108716939///398045
gsc: 397748///397752"
  },
  {
    "caption": "(D) NIH 3T3 cells transfected by equal amounts of plasmid fused with gfp (without ATG) to the sequence from 5' cap of pri-miR-31 to ATG site or which mutated to ATT of the sORF. Cells were selected by G418 for 2 days. Analysis of the GFP expression by confocal microscopy or flow cytometry, scale bar 100 μm.",
    "ncbi_link": "gfp: 
pri-miR-31: 723895"
  },
  {
    "caption": "(E) Immunoblot analysis of GFP and miPEP31 in NIH 3T3 cells transfected by pEGFP-N1-miPEP31 or pEGFP-N1, the red arrow indicate predicted size of miPEP31-GFP band.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "(F) Flow-fish to detect the localization of pri-miR-31. The location of pri-miR-31 was analyzed by confocal microscopy. Scale bar 5 μm.",
    "ncbi_link": "pri-miR-31: 723895"
  },
  {
    "caption": "(H) Immunoblot analysis of spleen, lymph node and thymus from WT or miR-31-/- mice with miPEP31 antibody, the red arrow indicate predicted size of miPEP31.",
    "ncbi_link": "miR-31: 723895"
  },
  {
    "caption": "(B, D) Yeast cells of the indicated genotype were transformed with plasmids coding for Atg5 and Atg16, respectively, and subjected to fractionation experiments. The proteins were detected by anti‐Myc western blotting. The presence of the protein in the pellet fraction indicated membrane binding.",
    "ncbi_link": "Atg16: 326115
Atg5: 855954"
  },
  {
    "caption": "(C) Quantification showing the relative amounts of Atg5-9 × Myc and Atg5-9 × Myc-Atg12 in the pellet fractions relative to Pex30. The amount of Atg5-9 × Myc and Atg5-9 × Myc-Atg12 in atg5Δ cells was set to 1. See Supplementary Figure 1 for graph based on non‐normed data. The quantification is based on three independent experiments and the averages and the standard deviations are shown. The numbers next to the blots indicate the molecular weight in kDa. P, pellet; S, supernatant. Figure source data can be found with the Supplementary data.",
    "ncbi_link": "Atg12: 852518
atg5: 855954"
  },
  {
    "caption": "(C) Yeast cells were transformed with the indicated expression constructs and Atg5-2 × Myc was immunoprecipitated with an anti‐Myc antibody. The precipitated protein was subjected to anti‐Atg5 and anti‐Atg12western blotting. The substitution of R171 and K160 to glutamate caused the mutant protein to run higher. The same phenomenon was observed for the recombinant protein ( Supplementary Figure 3).",
    "ncbi_link": "Atg5: 855954"
  },
  {
    "caption": "(E) Anti‐Myc and anti‐Pex30western blots of yeast cell fractions from cells of the indicated genotype and expressing Atg16 and Atg5 or Atg5 K160E, R171E.",
    "ncbi_link": "Atg5: 855954"
  },
  {
    "caption": "(A) Yeast cells of the indicated genotype expressing Atg5-3 × mCherry or Atg5 K160E, R171E-3 × mCherry were treated with rapamycin and imaged using a Deltavision microscope. Maximum projections of z‐stacks are shown.",
    "ncbi_link": "Atg5: 855954"
  },
  {
    "caption": "G The entry efficiency of SARS-CoV-2 and RshSTT182 pseudoviruses in HeLa-hACE2 cells. Green fluorescence indicates the entry of the pseudoviruses into the Hela-hACE2 cells. Unaltered HeLa cells were used as a negative control. H Statistics for transduction of pseudoviruses. Data represents the results of five replicates in one representative assay. All data are presented as mean ± SD. Pseudovirus infection assays were performed at least twice.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "B. RT-PCR analysis for forebrain (FOXG1), optic cup (VSX2), dorsal forebrain (PAX6 and EMX2) and ventral forebrain (NKX2-1) identity in organoids. All expression values (2-ΔCt) calculated relative to reference gene TBP. Analysis was performed on 5-6 organoids from multiple independent differentiations - control (7), dorsal (7), extended ventral (9) and short ventral (5). Significance values, * = <0.05, ** = <0.01, *** = <0.001. Statistical analysis was performed using one-way ANOVA and post-hoc Tukey's comparison of means. The central band depicts the median, the boxes depict values between lower and upper quartile and the whiskers display the minimum and maximum values.",
    "ncbi_link": "EMX2: 2018
FOXG1: 2290
NKX2-1: 7080
PAX6: 5080
TBP: 6908
VSX2: 338917"
  },
  {
    "caption": "C. UMAPs depicting the expression of GABAergic markers DLX2 and DLX5, progenitor marker TOP2A, MGE marker SOX6, CGE marker NR2F2, and striatal marker ZFHX3.",
    "ncbi_link": "DLX2: 1746
DLX5: 1749
NR2F2: 7026
SOX6: 55553
TOP2A: 7153
ZFHX3: 463"
  },
  {
    "caption": "C. UMAPs depicting the relative expression of migration genes CXCR4 and EPHA5. Visualization of the gene expression of migration genes CXCR4 and EPHA5 along the pseudotime axis. D. UMAPs depicting their relative expression of neurotransmitter genes GRIA4 and GRIA2 along with visualization of their gene expression along the pseudotime axis.",
    "ncbi_link": "CXCR4: 7852
EPHA5: 2044
GRIA2: 2891
GRIA4: 2893"
  },
  {
    "caption": "B, Representative contour maps of flow cytometry for FUCCI following the loss of NF2, PTPN14, TAOK1, CREBBP, and TP53.",
    "ncbi_link": "CREBBP: 1387
NF2: 4771
PTPN14: 5784
TAOK1: 57551
TP53: 7157"
  },
  {
    "caption": "B. Vero E6 cells were transfected with 10 nM of siRNA before infection by SARS-CoV-2 at a multiplicity of infection (MOI) of 0.1 after 24 h. The numbers of viral RNA copies were quantified with RT-qPCR. The negative control siRNA served as the control and is abbreviated as "Ctrl." C1-C11 represent the final candidate sequences after selection. The siRNAs capable of inhibiting up to 99% of viral envelope gene expression with P values < 0.005 compared with Ctrl siRNA are marked with *. P value by Student t test.",
    "ncbi_link": "envelope: 43740570
C1: 43740578
C11: 43740578"
  },
  {
    "caption": "E. IC50 of C6 and the fully modified C6G25S. Vero E6 cells were transfected with 10, 2, 0.4, 0.08, or 0.016 nM of C6 or C6G25S before virus infection at an MOI of 0.1. The viral RNA was quantified by RT-qPCR at 24 h after infection. F. IC50 data for viral RdRp inhibition by C6G25S. Vero E6 cells were transfected with 10, 2, 0.4, 0.08, or 0.016 nM of C6G25S before virus infection at an MOI of 0.1. The viral RNA was quantified by RT-qPCR at 24 h after infection. D",
    "ncbi_link": "RdRp: 43740578
C6: 43740578
C6G25S: 43740578"
  },
  {
    "caption": "B. IC50 for C6G25S against different variants. Vero E6 cells were transfected with 10, 2, 0.4, 0.08, or 0.016 nM of C6G25S before infection with different strains of SARS-CoV-2. The viral RNA was quantified by RT-qPCR at 24 h after infection. Data are presented as mean ± SD of three biological replicates.",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "A, B, C. K18-hACE2-transgenic mice treated with C6G25S by 1.48 mg/L of AI for 30 min (A), 50 μL of saline containing 50 μg of C6G25S by IN (B), or PBS (C) (n = 5 per group). C6G25S distribution in lungs was visualized by in situ hybridization (ISH) staining with C6G25S-specific probe (red color). Bronchi (i) and bronchioles (ii) marked with the boxes are enlarged on the right.",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "E, F. C57/B6 mice (n = 3 per group) were treated by AI with C6G25S 1.48 mg/L for 30 min (E) or 50 μL of saline containing 50 μg of C6G25S by IN administration (F). The C6G25S deposited in whole lungs and nasal cavities was quantified after whole tissue homogenization followed by stem-loop RT-qPCR. Quantification data represent mean ± SD. P value by Student t test.",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "A. K18-hACE2-transgenic mice (Winkler et al., 2020) were treated once daily for 3 days before intranasal challenge with 104 plaque-forming units (PFU) of the original virus. Prophylactic treatment consists of 30 min of AI (1.48 mg/l of C6G25S), followed by IN of 50 μg C6G25S. Mice receiving vehicle control (saline) for both AI and IN are annotated as control. Viral RNA (left) and infectious virions (right) in lungs were quantified with RT-qPCR and plaque forming assay, respectively, at 2 days post-infection (dpi). B. Mice were challenged intranasally with 104 PFU of virus and co-treatment with 1.48 mg/L of C6G25S or vehicle control (saline) by AI for 30 min on day 0 (right after infection) and day 1. Viral RNA and infectious virions were quantified at 2 dpi. C",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "A. Immunohistochemical (IHC) staining of viral spike proteins in lung sections from K18-hACE2 mice (Winkler et al., 2020) at day 5 post-infection. Spike proteins were detected with anti-spike antibody and stained brown. Images of bronchial epithelium of vehicle control treated (i and ii) and C6G25S treated (iii and iv), alveoli of vehicle control treated (v and vi) and C6G25S treated (vii and viii), bronchiole and blood vessel of vehicle control treated (ix and x) and C6G25S treated (xi and xii) group were shown. Syncytial cell was indicated by green arrow in (xi) and thrombosis in (x).",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "B. ISH staining of viral RNA in lungs of vehicle control group (left) and C6G25S treated group (right) at day 2 post-infection. Viral RNA was stained brown as green arrows indicated. Images are representative of 5 animals for each group.",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "C. Images of IHC staining of Ly6G+ Cells (Brown color, arrows indicated) in lungs of vehicle control (left) and C6G25S treated group (right) at day 2 post-infection.",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": "D. Images of IHC staining of F4/80+ Cells (Brown color) in lungs of vehicle control (left) and C6G25S treated group (right) at day 2 post-infection. E. Images of IHC staining of CD3 + T Cells (Brown color, arrows indicated) in lungs of vehicle control (left) and C6G25S treated group (right) at day 2 post-infection. F",
    "ncbi_link": "C6G25S: 43740578"
  },
  {
    "caption": " (B) Box plots show the MIG-6 (ERRFI1) gene expression in different breast tumor subtypes in the Servant dataset of 343 primary breast cancer carcinomas, analyzed using Illumina HumanWG-6_v3 Arrays. The gene expression levels are determined using the R2 Genomics Analysis and Visualization Platform (http://r2.amc.nl). In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median), and any outliers are shown as open circles. **p < 0.01, by Student's t-test. ",
    "ncbi_link": "ERRFI1: 54206
MIG-6: 54206"
  },
  {
    "caption": " (A) Cell proliferation and immunoblotting assays in BT549 cells with Luciferase or MIG-6 knockdown. ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (B) Cell proliferation and immunoblotting assays in MDA-MB-231 cells with Luciferase or MIG-6 knockdown. ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (C) Representative images and quantification results for a colony formation assay in BT549 cells with GFP or MIG-6 knockdown. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (D Immunoblotting analysis for EGFR signaling in BT549 cells with GFP or MIG-6 knockdown. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " E) Immunoblotting analysis for EGFR signaling in MDA-MB-231 cells with GFP or MIG-6 knockdown. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (F) Cell growth assay in BT549 cells with GFP or MIG-6 knockdown in the absence and presence of gefitinib for 72 hours. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (B) Extracellular acidification rate (ECAR) in BT549 cells with GFP or MIG-6 knockdown. The ECAR flux profile of GFP and MIG-6 knockdown BT549 cells upon stimulation of glucose, oligomycin, and 2-DG is shown on the left. Quantitative results for the basal glycolysis and maximal glycolysis capacities in GFP and MIG-6 knockdown BT549 cells are indicated by orange and green boxes, graphed on the right. Results are presented as mean ± SEM (n=15; biological replicates). ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (C) A heatmap diagram shows the expression profile of genes involved in glycolysis, the TCA cycle, the pentose phosphate pathway, pyruvate oxidation, gluconeogenesis, and glycogen metabolism obtained from two sets of GFP and MIG-6 knockdown BT549 cells. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " Histograms show the percentage of gene dysregulation in glycolysis, TCA cycle, upon MIG-6 knockdown in BT549 cells. For each gene, the change was calculated based on the equation: (shGFP-shMIG6)/shMIG-6. Results are presented as mean ± SEM (n=3; biological replicates). ",
    "ncbi_link": "GFP: 
MIG-6: 54206
MIG6: 54206"
  },
  {
    "caption": " F) Histograms show the percentage of pyruvate oxidation pathways upon MIG-6 knockdown in BT549 cells. For each gene, the change was calculated based on the equation: (shGFP-shMIG6)/shMIG-6. Results are presented as mean ± SEM (n=3; biological replicates). ",
    "ncbi_link": "GFP: 
MIG-6: 54206
MIG6: 54206"
  },
  {
    "caption": " (H) Lactate production assay in BT549 cells with GFP or MIG-6 knockdown (n=3). The medium was collected to measure lactate concentration using lactate test strips and an Accutrend Lactate analyzer. The rate of lactate production was determined (lactate production rate = lactate concentration/cells/time) and normalized to the rate detected in the control group. The quantified results are presented as mean ± SEM (n=3; biological replicates). ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (A) Box plots show the GLUT1 (SLC2A1) gene expression in different breast tumor subtypes in the Servant dataset of 343 primary breast cancer carcinomas, analyzed using Illumina HumanWG-6_v3 Arrays. The gene expression levels are determined using the R2 platform. In the box plot, error bars are the 95% confidence interval, the bottom and top of the box are the 25th and 75th percentiles, the line inside the box is the 50th percentile (median), and any outliers are shown as open circles. **p < 0.01, by Student's t-test.. ",
    "ncbi_link": "GLUT1: 6513
SLC2A1: 6513"
  },
  {
    "caption": "(B) Real-Time PCR analysis for GLUT1 and MIG-6 mRNA expression in GFP and MIG-6 knockdown BT549 cells (n=3).",
    "ncbi_link": "GFP: 
MIG-6: 54206
GLUT1: 6513"
  },
  {
    "caption": " (C) Immunoblotting analysis for GLUT1 protein expression in BT549 cells with GFP or MIG-6 knockdown. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (D) Confocal image analysis results for membrane-bound GLUT1 in GFP and MIG-6 knockdown BT549 cells are shown in the top panel. The arrow indicates membrane-localized GLUT1. Scale bar, 25 μm. Quantitative analysis results of the percentage of GFP and MIG-6 knockdown BT549 cells expressing membrane-localized GLUT1 are shown in the bottom panel (n=3). ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (E) Representative flow cytometry images (upper) and quantitative results (lower) of measuring glucose uptake in GFP and MIG-6 knockdown BT549 cells (n=3). Cells were grown in the presence of the fluorescent analog 2-NBDG for various time periods, and glucose uptake was quantified using flow cytometric analysis. The red box indicates the gating for 2-NBDG+ cells and the number indicates the percentage of 2-NBDG+ cells. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (F) Immunoblotting analysis for GLUT1 protein expression in GFP and MIG-6 knockdown BT549 cells with or without MG132 treatment. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (B) Immunoblotting analysis for HIF1α protein expression in BT549 cells with GFP or MIG-6 knockdown. (C) Immunoblotting analysis for HIF1α protein expression in MDA-MB-231 cells with GFP or MIG-6 knockdown. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (D) Real-Time PCR analysis for HIF1α mRNA expression in BT549 cells with GFP or MIG-6 knockdown. The quantified results are presented as mean ± SD (n=4). ***p < 0.001, by Student's t-test. ",
    "ncbi_link": "GFP: 
MIG-6: 54206
HIF1α: 3091"
  },
  {
    "caption": " (E) Immunoblotting analysis for HIF1α protein expression in GFP and MIG-6 knockdown BT549 cells in the absence or presence of the proteasome inhibitor MG132. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (F) GFP and MIG-6 knockdown BT549 cells transfected with the indicated plasmids were treated with MG132, subjected to immunoprecipitation (IP) with Flag-tag or HIF1α antibody, followed by immunoblotting analysis. MG132 was used to rescue HIF1α protein degradation mediated by MIG-6 knockdown, leading to similar HIF1α protein levels in control and MIG-6 knockdown BT549 cells, which were used as the input to examine the role of MIG-6 in the interaction between HIF1α and HAUSP. ",
    "ncbi_link": "GFP: 
MIG-6: 54206"
  },
  {
    "caption": " (G) Luciferase and MIG-6 knockdown 293 cells were transfected with the indicated plasmids and subjected to MG132 treatment. Afterward, cells were harvested for IP with HA antibody, followed by immunoblotting analysis to determine the level of K48-linked ubiquitination of HIF1α. MG132 was used to preserve the degradative K48-linked ubiquitination signals. ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (H) Immunoblotting analysis for MIG-6 and HIF1α expression in Luciferase and MIG-6 knockdown 293 without MG132 treatment. ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (I) Immunoblotting analysis for GLUT1 protein expression upon MIG-6 overexpression in GFP and HIF1α knockdown BT549 cells. ",
    "ncbi_link": "GFP: 
MIG-6: 54206
HIF1α: 3091"
  },
  {
    "caption": " (J) Immunoblotting analysis for GLUT1 protein expression upon MIG-6 overexpression in GFP and HAUSP knockdown BT549 cells. ",
    "ncbi_link": "GFP: 
MIG-6: 54206
HAUSP: 7874"
  },
  {
    "caption": " (K) Immunoblotting analysis for HIF1α protein expression upon HAUSP overexpression in GFP and MIG-6 knockdown BT549 cells. ",
    "ncbi_link": "GFP: 
MIG-6: 54206
HAUSP: 7874"
  },
  {
    "caption": " (A and B) Lactate production assay in BT549 (A) and MDA-MB-231 (B) cells with Luciferase or GLUT1 knockdown. ",
    "ncbi_link": "Luciferase: 
GLUT1: 6513"
  },
  {
    "caption": " (C) Cell proliferation assay in BT549 cells with Luciferase or GLUT1 knockdown. ",
    "ncbi_link": "Luciferase: 
GLUT1: 6513"
  },
  {
    "caption": " (D) Cell proliferation assay in MDA-MB-231 cells with GFP or GLUT1 knockdown. ",
    "ncbi_link": "GFP: 
GLUT1: 6513"
  },
  {
    "caption": " (E and F) Immunoblotting analysis for GLUT1 protein expression in control and MIG-6 knockdown BT549 (E) and MDA-MB-231 (F) cells with or without GLUT1 overexpression. ",
    "ncbi_link": "MIG-6: 54206
GLUT1: 6513"
  },
  {
    "caption": " (G Lactate production assay in control and MIG-6 knockdown BT549 cells with or without GLUT1 overexpression. ",
    "ncbi_link": "MIG-6: 54206
GLUT1: 6513"
  },
  {
    "caption": " H) Lactate production assay in control and MIG-6 knockdown MDA-MB-231 cells with or without GLUT1 overexpression. ",
    "ncbi_link": "MIG-6: 54206
GLUT1: 6513"
  },
  {
    "caption": " (I and J) Cell proliferation assay in BT549 (I) and MDA-MB-231 (J) cells with control knockdown, MIG-6 knockdown, or MIG-6 knockdown plus GLUT1 overexpression. ",
    "ncbi_link": "MIG-6: 54206
GLUT1: 6513"
  },
  {
    "caption": " (A and B) In vivo primary tumor growth derived from BT549 cells with Luciferase or MIG-6 knockdown (six mice per group). Cells were injected into the mammary fat pads of nude mice, and tumor sizes were measured weekly by caliper. Kaplan-Meier plot analysis is used to determine the incidence of Luciferase or MIG-6 knockdown BT549-xenograft tumors (A). Volumes of Luciferase or MIG-6 knockdown BT549 tumors at week 10 are presented as mean ± SEM (B). ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (C In vivo primary tumor growth derived from MDA-MB-231 cells with Luciferase or MIG-6 knockdown (nine mice per group). Volumes of Luciferase or MIG-6 knockdown MDA-MB-231 tumors were measured weekly by caliper are presented as mean ± SEM ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " D) In vivo primary tumor derived from MDA-MB-231 cells with Luciferase or MIG-6 knockdown (nine mice per group). Tumor weights of MDA-MB-231-derived xenografts were measured at the endpoint (day 33) and are presented as mean ± SEM (D). ",
    "ncbi_link": "Luciferase: 
MIG-6: 54206"
  },
  {
    "caption": " (E) Immunoblotting analysis for MIG-6 expression in BT549 cells with MIG-6 inducible knockdown (iMIG-6-shRNA) and the non-targeting shRNA control (iNT-shRNA) upon doxycycline treatment. ",
    "ncbi_link": "MIG-6: 54206"
  },
  {
    "caption": " (F) In vivo primary tumor growth derived from BT549 cells containing iNT-shRNA and iMIG-6-shRNA (n=7 per group). The arrow indicates the time point when the diet was given to induce MIG-6 knockdown in vivo. Volumes of iNT-shRNA and iMIG-6-shRNA BT549 tumors are presented as mean ± SEM. ",
    "ncbi_link": "MIG-6: 54206"
  },
  {
    "caption": "(A) Representative images of histological analysis for GLUT1 protein expression in BT549-derived xenograft tumors. Scale bar, 100 μm. (B) Representative images of histological analysis for GLUT1 protein expression in xenograft tumors derived from BT549 cells containing iNT-shRNA and iMIG-6-shRNA. Scale bar, 100 μm.",
    "ncbi_link": "MIG-6: 54206"
  },
  {
    "caption": "(a) Expression of H2B-mCherry under control of the CLV3 promoter in 14-d-old seedlings. Whole-mount immunostaining using α-mCherry antibodies and laser scanning microscopy (scale bar 10 μm).",
    "ncbi_link": "CLV3: 817267"
  },
  {
    "caption": "(c) A representative example for enrichment of CLV3 transcript in mCherry-positive nuclei determined by qRT-PCR and normalized to wt (N = 1).",
    "ncbi_link": "mCherry: 
CLV3: 817267"
  },
  {
    "caption": "(a) Expression of CLV3, mCherry, TEL2, PAN, and the meristem marker genes STM and KNAT1. Asterisks indicate timepoints of significantly different expression (Wald test, Benjamini & Hochberg corrected, q<0.05) between stem and non-stem cells for each time point (N = 2). + = stem cell nuclei; - = non-stem cell nuclei, E = nuclei from embryos, D7/14/35 = nuclei from 7/14/35 day-old plants, S14 = nuclei from 14 d-old above-ground seedlings.",
    "ncbi_link": "mCherry: 
CLV3: 817267
KNAT1: 826364
PAN: 843194
STM: 842534
TEL2: 843102"
  },
  {
    "caption": "(a) Increased expression of TEs in stem cells of D7 seedlings according to qRT-PCR. Box plots outline the interquartile range (IQR) with the median and whiskers +/- 1.5 IQR. N = 2 (ATLANTYS3, ATCOPIA39, ATCOPIA49, ATCOPIA29, ATGP1-1), N = 3 (VANDAL6, ATGP2, ATGP1-2, ATLINE1, ATGP1-3), N = 4 (ATHILA6A, ATCOPIA83), N = 5 (VANDAL12, ATHILA3, ATCOPIA22), and N = 6 for CLAVATA. *p<0.01, **p<0.001 (t-test).",
    "ncbi_link": "ATCOPIA83: 
ATGP1-1: 
ATHILA3: 
ATHILA6A: 
VANDAL12: 
ATCOPIA22: 
ATCOPIA29: 
ATCOPIA39: 
ATCOPIA49: 
ATGP1-2: 
ATGP1-3: 
ATGP2: 
ATLANTYS3: 
ATLINE1: 
CLAVATA: 
VANDAL6: "
  },
  {
    "caption": "(b) Heatmap of TE expression in several silencing mutants determined by qRT-PCR relative to a housekeeping gene. To be able to display data in log-scale also for samples with zero expression, a value of 1.0e-6 (factor 10 smaller than the smallest value) was added to all values. Data for nuclei and CLV3::H2BmCherry are the same as in (a). For seedling samples, N = 2 (ATCOPIA49, ATHILA3), N = 3 (ATCOPIA39, VANDAL6, ATGP2, ATLINE1, ATCOPIA29, ATGP1-1), and N = 4 (ATLANTYS3, VANDAL12, ATGP1-2, ATHILA6A).",
    "ncbi_link": "ATCOPIA29: 
ATCOPIA39: 
ATCOPIA49: 
ATGP1-1: 
ATGP1-2: 
ATGP2: 
ATHILA3: 
ATHILA6A: 
ATLANTYS3: 
ATLINE1: 
VANDAL12: 
VANDAL6: 
mCherry: 
CLV3: 817267
H2B: 832352"
  },
  {
    "caption": "TCF-reporter TOP-flash assay performed on the indicated cell lines treated with 10 μM CHIR, for 24 hrs. The control FOP-flash reporter is not activated upon CHIR administration. The data represent the mean ± s.e.m. of averages of nine independent experiments (N = 9). dBcat, β-catenin knockout cells; d4TCF, TCF/LEF quadruple knockout cells Transfection of individual TCF-expressing plasmids could restore the ability of d4TCF cells to respond to Wnt3 as measured in a TOP-flash assa",
    "ncbi_link": "β-catenin: 1499
LEF: 51176
TCF: 6932
TCF: 83439"
  },
  {
    "caption": "Quantitative RT-PCR analyses of Axin2 transcripts, performed on the different cell lines treated with 10 μM CHIR or DMSO (control) for 24 hrs. Error bars show that standard deviation obtained from 3 independent experiments Transfection of individual TCF-expressing plasmids could restore the ability of d4TCF cells to respond t CHI as measured by Axin2 mRNA abundance",
    "ncbi_link": "Axin2: 8313
TCF: 6932"
  },
  {
    "caption": "(A, B) β-catenin occupancy on regulatory regions of the prototypical Wnt target genes, AXIN2 and LEF1 (A), and at the promoter regions of HOXC4 and ZNF503 (B)",
    "ncbi_link": "AXIN2: 8313
HOXC4: 3221
LEF1: 51176
ZNF503: 84858"
  },
  {
    "caption": "(C) β-catenin ChIP-seq enrichment over ENCODE TCF7L2 (also known as TCF4) ChIP peaks in HEK293T cells. The data represent the mean ± 95% C.I. obtained from three independent experiments (N = 3)",
    "ncbi_link": "TCF4: 6934
TCF7L2: 6934"
  },
  {
    "caption": "b RT-qPCR validation of the β-catenin-GHOST response. A selection of 7 genes (colour coded) that are activated upon CHIR treatment in d4TCF, or in wild-type (WT) in combination with ICAT overexpression, but not in pentaKO cells - indicating that their regulation is dependent on β-catenin but can only occur in the absence of TCF/LEF-β-catenin interaction. The genotype and the treatment for each condition is indicated in the x-axis. Error bars show that standard deviation obtained from 3 independent experiments",
    "ncbi_link": "β-catenin: 1499
ICAT: 56998"
  },
  {
    "caption": "c FOXO4 but not FOXO3 overexpression upregulates the β-catenin-GHOST target GADD45 both in CHIR-treated WT (black bars) or d4TCF (grey bars) cells. Samples were compared using Student\"s t-test. Asterisks (*) indicate a p-value<",
    "ncbi_link": "FOXO3: 2309
FOXO4: 4303
GADD45: 10912///1647///4616"
  },
  {
    "caption": "d FOXO4 overexpression induced GADD45 transcription in WT (black bars) but not in dBcat (grey bars) cells. Samples were compared using Student\"s t-test. Asterisks (*) indicate a p-value<",
    "ncbi_link": "FOXO4: 4303
GADD45: 4616///1647///10912"
  },
  {
    "caption": "e Endogenous FOXO4, when immunoprecipitated (IP) pulls down β-catenin. Overexpressed FOXO4 increases the amount of β-catenin detected in the immunoprecipitated, indicating physical association",
    "ncbi_link": "FOXO4: 4303"
  },
  {
    "caption": "f GADD45 is upregulated by CHIR in d4TCF cell; this positive transcriptional regulation is blocked by FOXO4-specific siRNA but not control scrambled siRNA. All experiments were done at least three times (N=3). Samples were compared using Student\"s t-test. Asterisks (**) indicate a p-value<0.02; ns, non-statistically significant change was obs",
    "ncbi_link": "FOXO4: 4303
GADD45: 4616///1647///10912"
  },
  {
    "caption": "(C) Time-lapse microscopy of cells containing a PsigV-YFP promoter reporter reveals heterogeneous activation of σV in response to lysozyme stress. The stress (red line) was added between the 200 mins and 300 min time points (at 240 min). The red arrow highlights a cell with a delayed activation of σV. Scale bar: 5 μm.",
    "ncbi_link": "YFP: 
sigV: 937591"
  },
  {
    "caption": "(B, C) RNA-seq experiment on WT (JLB130) and ΔsigV (JLB154) strains, showing quantification of the absolute expression of individual genes in the presence and absence of lysozyme stress. The shaded grey box represents a ± 5 fold change. DEseq was used to identify genes which were differentially expressed with a 5% p-value cutoff between the WT and ΔsigV mutant in response to lysozyme treatment (default DEseq test was used). (B) Only the sigV operon is strongly activated (>5 fold change) in response to lysozyme stress in WT (JLB130), as previously reported (Guariglia-Oropeza and Helmann 2011). (C) No genes were strongly upregulated in ΔsigV (JLB154) by lysozyme stress.",
    "ncbi_link": "sigV: 937591"
  },
  {
    "caption": "(D) Effect of the overexpression of individual components of the σV pathway (Biological repeats: WT: n=8, sigV+: n=4, rsiV+: n=3 oatA+: n=4, yrhK+: n=3, sipS+: n=3 and rasP+: n=3, pbpX+: n=6) on the fraction of activated cells. Only overexpression of sigV, rsiV or oatA changed the observed dynamics compared to WT. The histograms of the shown data are shown in Appendix Figure S16. (E) Deleting oatA did not alter the σV activation dynamics. However, deleting sigV or rsiV resulted in no further activation of σV in response to 1 ug/ml lysozyme. n>=3 biological repeats for all data shown. The histograms of the shown data are shown in Appendix Figure S17. ( ",
    "ncbi_link": "oatA: 936583
pbpX: 939677
rasP: 939612
rsiV: 937593
sigV: 937591
sipS: 938944
yrhK: 937587"
  },
  {
    "caption": "(C) As predicted, the 2xsigV or 2xsigV-rsiV stains have a homogenous σV response to 1 µg/ml lysozyme, while the 2xrsiV strain has increased heterogeneity. Each bar plot is the average of three biological repeats. The bars correspond to the mean ± s.d..",
    "ncbi_link": "rsiV: 937593
sigV: 937591"
  },
  {
    "caption": "(C) Expression of miRNAs miR-146a and miR-505 correlated with overall survival in ovarian cancer patients. The validation cohort (n=150 samples) is shown. See Figure EV1 for the training cohort.",
    "ncbi_link": "miR-146a: RF00691
miR-505: RF00781"
  },
  {
    "caption": "(A) The consequence of miR-155 and miR-181b mimics on cell viability, 5 days post transfection, relative to a negative control miRNA mimic is shown across a panel of normal and ovarian cancer cell lines as indicated. Each data point is the mean of n=3/cell line. In the screen, miR-155 was found to reduce cell viability (Z-score < -2) in one cell line, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors. miR-181 was found to reduce viability (Z-score < -2) in 2 cell lines, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors. N, normal cell lines (IHH, HOSE, HBEC3, HBEC13, HBEC30, and HBEC34), EOC, epithelial ovarian cancer cell lines. miR-155 data points for each cell line are shown in black while miR-181b data points are displayed in red.",
    "ncbi_link": "miR-155: RF00731
miR-181: RF00076
miR-181b: RF00076"
  },
  {
    "caption": "(B) Immunoblots indicate suppression of serum-induced AKT phosphorylation at S473 and T308 in response to miR-155 and suppression of T308 phosphorylation in response to miR-181b.",
    "ncbi_link": "miR-155: RF00731
miR-181b: RF00076"
  },
  {
    "caption": "(C) miR-155 and miR-181b reduced cell viability in GDC0941-sensitive breast cancer cell lines. Error bars indicate mean ± SD (n=3).",
    "ncbi_link": "miR-155: RF00731
miR-181b: RF00076"
  },
  {
    "caption": "(F) Cell viability upon expression of miR-155 or miR-181a mimics in 41 NSCLC cell lines and 5 human bronchial epithelial cell lines. Each data point is the mean of n=3/cell line. R2 from Pearson correlation.",
    "ncbi_link": "miR-155: RF00731
miR-181a: RF00076"
  },
  {
    "caption": "(A) Consequence of miR-517a on EOC cell viability and 41 NSCLC cell lines (as in 2A). N, normal cell lines (IHH, HOSE, HBEC3, HBEC13, HBEC30, and HBEC34). miR-517a was found to significantly reduce cell viability (Z-score < -2) in 5 cell lines in the screen, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors.",
    "ncbi_link": "miR-517a: 574479"
  },
  {
    "caption": "(B, C) In vivo delivery of neutral liposome incorporated miR-517a mimic reduced tumor burden by weight (B) and nodule number (C) in an orthotopic xenograft model using SKOV3 cells. Box-and-whisker plot from n=8. p-value from Student's T-Test. LD, low-dose (200 μg/kg); HD, high-dose (400 μg/kg).",
    "ncbi_link": "miR-517a: 574479"
  },
  {
    "caption": "(D) Correlation of the consequence of ARCN1 depletion and miR-517a sensitivity in 12 NSCLC cell lines (plot as in 2D).",
    "ncbi_link": "ARCN1: 372
miR-517a: 574479"
  },
  {
    "caption": "(E) Immunoblots indicate miR-517a-induced depletion of ARCN1 and USP1 in the indicated cell lines.",
    "ncbi_link": "miR-517a: 574479"
  },
  {
    "caption": "(F) Consequence of the indicated siRNAs and miR-517a on the viability of the indicated cell lines.",
    "ncbi_link": "miR-517a: 574479"
  },
  {
    "caption": "(G) Immunoblots indicate that miR-517a suppresses expression of ARCN1 in multiple miR-517a sensitive cell lines.",
    "ncbi_link": "miR-517a: 574479"
  },
  {
    "caption": "(A) Consequence of miR-124 on EOC cell viability (as in 2A). N, normal cell lines (IHH and HOSE). In the screen, miR-124 was found to significantly reduce cell viability (Z-score < -2) in 6 cell lines, and TCGA expression data revealed no significant change in expression of this miRNA in ovarian tumors.",
    "ncbi_link": "miR-124: RF00239"
  },
  {
    "caption": "(B) miR-124 induced expression of neuronal marker proteins Tuj1 (TUBB3) and MAP2 in ES2 cells 48 hours post transfection. Cells were counterstained with DAPI and phalloidin.",
    "ncbi_link": "miR-124: RF00239"
  },
  {
    "caption": "(C) miR-124 responsive genes in PEO1 cells were enriched for TargetScan predicted targets. p-value from hypergeometric distribution.",
    "ncbi_link": "miR-124: RF00239"
  },
  {
    "caption": "(A) Immunoblots indicate miR-124-induced SIX4 depletion. siSIX4 is shown as an antibody control.",
    "ncbi_link": "miR-124: RF00239
SIX4: 51804"
  },
  {
    "caption": "(B) Consequence of SIX4 depletion on EOCcell viability (as in 2A, N, normal cell lines: HOSE, HBEC30).",
    "ncbi_link": "SIX4: 51804"
  },
  {
    "caption": "(C) in vivo knockdown of SIX4 using neutral liposome incorporated siRNA reduced tumor burden and ascites volume in an orthotopic xenograft mouse model. Box-and-whisker plot from n=8. p-value from Student's T-Test.",
    "ncbi_link": "SIX4: 51804"
  },
  {
    "caption": "(D) Consequence of SIX4 depletion in PEO1 cells on E-cadherinplasma membrane accumulation 48 hours after transfection. Cells were counterstained with phalloidin and DAPI.",
    "ncbi_link": "SIX4: 51804"
  },
  {
    "caption": "(E) Immunoblots indicate consequence of SIX4 depletion on LKB1 accumulation and AMPK pathway activation.",
    "ncbi_link": "SIX4: 51804"
  },
  {
    "caption": "PMN were treated with either an shRNA targeting IGF1R (1 µl) or a scrambled control 6 h after plating. At DIV 6-7, retrograde axonal transport was analysed using 30 nM AlexaFluor555-HcT. Knockdown of IGF1R caused a significant increase in the average velocity of signalling endosomes compared to controls (IGF1R shRNA: 108 endosomes, 21 axons, 801 movements; scrambled shRNA: 94 endosomes, 20 axons, 777 movements, * P=0.011, Student's T-test, N=3 independent experiments, boxplot shows median, first and third quartiles. Upper/lower whiskers extend to 1.5 * the interquartile range). Speed distribution profile including pausing events of PMN treated with a shRNA targeting IGF1R or a scrambled control. IGF1R knockdown caused an increase in instantaneous velocities of HcT-containing organelles and decreased the amount of pausing (N=3 independent experiments, data shown are mean ± SEM).",
    "ncbi_link": "IGF1R: 16001"
  },
  {
    "caption": "The graph shows the average velocity of HcT-containing organelles in vivo in D72/73 SOD1G93A mice and wild type littermate controls. PPP (blue) treatment increased the transport rate of signalling endosomes in wild type and SOD1G93A mice compared to animals treated with vehicle control (grey) (WT control: cargo 371, movements 15,272, N=4 independent experiments; WT + PPP: cargo 388, movements 14,512, N=4 independent experiments; SOD1G93A control: cargo 322, movements 15,425, N=4 independent experiments; SOD1G93A + PPP: cargo 404, movements 17,643, N=4 independent experiments; P=2.24x10-12 (treatment), P=2.22 x10-16 (genotype), two-way ANOVA, Tukey's post-hoc test: all conditions *** P<0.005, boxplot shows median, first and third quartiles. Upper/lower whiskers extend to 1.5 * the interquartile range). PPP treatment does not alter the pausing of signalling endosomes (WT: 16.1 ± 1.5%, WT + PPP: 13.1 ± 1.5%; SOD1G93A: 16.6 ± 1.9%, SOD1G93A + PPP: 16.2 ± 2.1%; P=0.36 (treatment), P=0.32 (genotype), N=4 independent experiments for each condition, data shown are mean ± SEM.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "Treatment with PPP had no effect on Akt levels in the sciatic nerve (WT: Control-100 ± 8.6, PPP-91.5 ± 14.6%; SOD1: Control-101.4 ± 13.5%, PPP-117.6 ± 32.9%, P=0.81 (treatment), P=0.53 (genotype), two-way ANOVA, N=5 independent experiments, data shown are mean ± SEM, Appendix Fig S7D). Erk1/2 activation was down-regulated after treatment with PPP in the sciatic nerve of wild type and SOD1G93A mice (WT: control-100 ± 15.4%, PPP-64.4 ± 3.2%; SOD1: Control-78.0 ± 11.9 %, PPP-51.2 ± 8.2%, * P=0.013 (treatment), P=0.13 (genotype), two-way ANOVA, N=5 independent experiments, data shown are mean ± SEM, Appendix Fig S7D). Protein was normalised to GAPDH protein levels.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "a-c, RFA1::FLAG DDC2::MYC cells were arrested in G2 and released in YP galactose to induce HO endonuclease. After 30 min, the culture was split in two: +VPA and -VPA. a, Samples were processed for western blot using anti-Rad53, Srs2 and Ddc2 antibodies.",
    "ncbi_link": "DDC2: 852110
RFA1: 851266"
  },
  {
    "caption": "a-c, RFA1::FLAG DDC2::MYC cells were arrested in G2 and released in YP galactose to induce HO endonuclease. After 30 min, the culture was split in two: +VPA and −VPA. b, A schematic diagram showing probe locations with respect to the HO cut site. The resection rate was calculated as the rate of HO cut band disappearance.",
    "ncbi_link": "DDC2: 852110
RFA1: 851266"
  },
  {
    "caption": "a-c, RFA1::FLAG DDC2::MYC cells were arrested in G2 and released in YP galactose to induce HO endonuclease. After 30 min, the culture was split in two: +VPA and -VPA. c, Fold enrichment of the 0.2-kb fragment was calculated after ChIP of Rfa1-Flag, Ddc2-Myc.",
    "ncbi_link": "DDC2: 852110
RFA1: 851266"
  },
  {
    "caption": "a, MRE11::MYC cells were treated as in Fig. 1a. Cell samples were processed for ChIP analysis and the fold enrichment of the 0.2-kb fragment after ChIP of Mre11-Myc without (-VPA) or with (+VPA) VPA was calculated.",
    "ncbi_link": "MRE11: 855264"
  },
  {
    "caption": "b, EXO1::FLAG SAE2::PK MRE11::MYC cells were grown as in a. Cell samples were taken and processed for western blot analysis using anti-Flag, PK and Myc antibodies.",
    "ncbi_link": "EXO1: 854198
MRE11: 855264
SAE2: 852700"
  },
  {
    "caption": "a, Cherry::APE1GFP::ATG8 cells were grown and shifted to YPD, nitrogen starvation (SD-N) or YPD+VPA medium for 3 h. Samples were processed for microscopy. The table shows numbers corresponding to the experiment. Percentage of fluorescence signals is presented and error bars represent the s.d. obtained from three independent experiments. DIC, differential interference contrast. Scale bars, 3 µm.",
    "ncbi_link": "APE1: 853758
ATG8: 852200"
  },
  {
    "caption": "b, pho8Δ60 and pho8Δ60 atg1Δ; cells were grown as in a. Pho8Δ60 activity was calculated by measuring alkaline phosphatase levels. Error bars represent s.d. calculated from five independent experiments.",
    "ncbi_link": "atg1: 852695
pho8: 852092"
  },
  {
    "caption": "c, GFP::ATG8 and GFP::ATG8atg1Δ; cells were grown as in a. Cell samples were processed for western blot using anti-GFP antibody. Quantification is presented in Supplementary Fig. 3.",
    "ncbi_link": "atg1: 852695
ATG8: 852200"
  },
  {
    "caption": "b, SAE2::PKerg6Δ cells were treated as in Fig. 2a. After 30 min induction, VPA and PMSF were added or not. Samples were processed for western blot using anti-PK.",
    "ncbi_link": "erg6: 855003
SAE2: 852700"
  },
  {
    "caption": "c, Wild-type SAE2::PK, SAE2::PKatg1Δ and SAE2::PKatg19Δ cells were grown as in b. After 30 min induction, VPA was added or not and samples treated as in b.",
    "ncbi_link": "atg1: 852695
atg19: 854072
SAE2: 852700"
  },
  {
    "caption": "d, Wild-type SAE2::PK cells were grown as in b. After 120 min induction, rapamycin (200 ng ml-1) was added or not and samples were treated as in b.",
    "ncbi_link": "SAE2: 852700"
  },
  {
    "caption": "a, Survival of wild-type, rpd3Δ, hda1Δ and rpd3Δ hda1Δ strains after 4NQO, MMS and HU treatment. Error bars represent s.d. calculated from seven independent experiments.",
    "ncbi_link": "hda1: 855710
rpd3: 855386"
  },
  {
    "caption": "b, HO was induced in G2 wild-type, hda1Δ, rpd3Δ and hda1Δ rpd3Δ cells and western and Southern blot analyses were performed.",
    "ncbi_link": "hda1: 855710
rpd3: 855386"
  },
  {
    "caption": "c, Wild-type SAE2::PK and hda1Δ rpd3Δ SAE2::PK cells were grown as in b and western blot was performed as in Fig. 4b.",
    "ncbi_link": "hda1: 855710
rpd3: 855386
SAE2: 852700"
  },
  {
    "caption": "d, e, Wild-type SAE2::PK and gcn5Δ SAE2::PK strains were grown as in b and after 30 min of HO induction either VPA (d) or rapamycin (e) was added or not. Western blot was performed.",
    "ncbi_link": "gcn5: 853167
SAE2: 852700"
  },
  {
    "caption": "f, Percentage of viability of wild-type, atg1Δ, rpd3Δ hda1Δ and atg1Δ rpd3Δ hda1Δ strains. Error bars represent s.d. calculated from four independent experiments.",
    "ncbi_link": "atg1: 852695
hda1: 855710
rpd3: 855386"
  },
  {
    "caption": "(F) Quantification of CXCL10 and IFIT1 transcripts by qPCR of the indicated THP-1 cell lines stimulated for 24 hours with LPS (1 ng/ml) normalised to mock. Mean data n=2 biological replicates.",
    "ncbi_link": "CXCL10: 3627
IFIT1: 3434"
  },
  {
    "caption": "(H) Quantification of the indicated chemokine transcripts by qPCR from PMA-treated THP-1/SAMHD1 KO cells transduced for 24 hours with 50ng/RT of the indicated HIV-1 GFP capsids mutants normalised to mock infected. Mean data represent n=3 biological replicates.",
    "ncbi_link": "GFP: 
capsids: 155348
SAMHD1: 25939"
  },
  {
    "caption": "(I-J) Protein quantification of CXCL10 (I) and TNFa (J) by Luminex™ from supernatant of PMA-treated THP-1/SAMHD1 KO cells infected with the indicated HIV-1 mutants. Data were normalised to mock. Mean data represent n=2 biological replicates.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "(D) qPCR quantification of the indicated chemokine transcripts from PMA-treated THP-1/SAMHD1 KO cells transduced for 24 hours with the indicated VLPs mutants. (E) qPCR quantification of the indicated chemokine transcripts level from PMA-treated THP-1/SAMHD1 KO cells transduced for 24 hours with 50ng/RT of the indicated HIV-1 GFP capsids mutants.",
    "ncbi_link": "GFP: 
capsids: 155348
SAMHD1: 25939"
  },
  {
    "caption": "(F) Protein quantification of IL-6 by Luminex™ from PMA-treated THP-1/SAMHD1 KO cells infected with the indicated HIV-1 mutants.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "IFIT1-Luc reporter activity from PMA-treated THP-1/SAMHD1 KO cells stimulated by transfection with either poly I:C (0.5 μg/ml) (B) mean data represent n=2 biological replicates",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "IFIT1-Luc reporter activity from PMA-treated THP-1/SAMHD1 KO cells stimulated by transfection with HT-DNA (0.1 μg/ml) (C) mean data represent n=2 biological replicates",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "IFIT1-Luc reporter activity from PMA-treated THP-1/SAMHD1 KO cells stimulated by transfection infected for 24 hours with 50ng/RT of the indicated HIV-1 GFP capsids mutants (D).",
    "ncbi_link": "GFP: 
capsids: 155348
SAMHD1: 25939"
  },
  {
    "caption": "IFIT1-Luc reporter activity from PMA-treated THP-1/SAMHD1 KO infected with for 24 hours with 50ng/RT of the indicated HIV-1 GFP capsids mutants in the presence of DMSO or 0.5 μg/ml H151 (E)",
    "ncbi_link": "GFP: 
capsids: 155348
SAMHD1: 25939"
  },
  {
    "caption": "B, C. Immunoprecipitation of endogenous Sufu from PC3 (B) and DAOY cells (C) transfected with either an empty vector (EV) or Myc-tagged Fbxl17. Non-specific rabbit immunoglobulin G (IgG) was used as a negative control. Detection of light chains of immunoglobulin (IgG) was used to assess the amount of IgG used for each immunoprecipitation reaction. Treatment with MLN4924 (2 M) was started 5 hours before cell collection.",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "D. Quantification of Fbxl17 mRNA levels in PC3 and DAOY transfected with a non-targeting siRNA (Control) or two siRNAs to Fbxl17 (1) and (2). Cells were serum starved for 24 hours in serum-reduced medium and treated with SAG (100 nM) for 24 hours prior collection.",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "F. Sufu protein levels in PC3 and DAOY cells infected with an empty backbone retrovirus (EV) or a retrovirus expressing Myc-tagged Fbxl17. Representative image from three independent experiments is shown.",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "G. Detection of Sufu protein levels following cycloheximide (CHX) treatment for the indicated hours, and Fbxl17 depletion using two different siRNAs. (Hrs=hours). Representative image of two independent experiments is shown",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "A. Detection of polyubiquitylated species of endogenous Sufu co-immunopurified from DAOY cells transfected with Myc-tagged ubiquitin (Ub) either in the presence of non-targeting siRNA (Control) or two siRNAs against Fbxl17 (1) and (2). MG132 (10µM) was added in all samples.",
    "ncbi_link": "Fbxl17: 64839
ubiquitin: 7311///6233///7316///7314"
  },
  {
    "caption": "B. Detection of polyubiquitylated species of Sufu upon co-transfection of HEK293T cells with HA-tagged Sufu and Myc-tagged ubiquitin (Ub) either in the presence of non-targeting siRNA (Control) or two siRNAs against Fbxl17 (1) and (2). MG132 (10µM) was added in all samples.",
    "ncbi_link": "Fbxl17: 64839
Sufu: 51684
ubiquitin: 7311///6233///7316///7314"
  },
  {
    "caption": "C. Fbxl17 mRNA relative levels in DAOY and HEK293T cells upon Fbxl17 depletion with either a non-targeting siRNA (Control) or two siRNAs to Fbxl17 (1) and (2).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "D. Detection of ubiquitylated Sufuco-immunoprecipitated from HEK293T cells co-transfected with HA-tagged Sufu, Myc-ubiquitin (Ub) along with either Flag-tagged Fbxl17 wild type (WT) or a mutant lacking the F-box domain (Fbxl17ΔF). MG132 (10µM) was added in all samples.",
    "ncbi_link": "Fbxl17: 64839
Sufu: 51684
ubiquitin: 7314///7311///6233///7316"
  },
  {
    "caption": "E. Detection of ubiquitylated Sufuco-immunoprecipitated from HEK293T cells co-transfected with Myc-tagged ubiquitin (Ub), Flag-tagged Fbxl17 and HA-tagged Sufu WT or Sufu mutant K257R. MG132 (10µM) was added in all samples.",
    "ncbi_link": "Fbxl17: 64839
Sufu: 51684
ubiquitin: 7314///7311///6233///7316"
  },
  {
    "caption": "A. Detection of Myc-tagged Fbxl17 after immunoprecipitation of HA-tagged Sufu WT or Sufu S342/6A and S342/6D, as indicated. HEK293T cells were treated with MLN4924 (2 M) for 5 hours prior collection.",
    "ncbi_link": "Sufu: 51684"
  },
  {
    "caption": "B. Detection of Flag-tagged Gli1 and Myc-tagged Fbxl17 binding to immunoprecipitated HA-tagged Sufu Wild-Type (WT) or to Sufu S352F. An Empty Vector (EV) was used as a negative control. HEK293T cells were treated with MLN4924 (2 M) for 5 hours prior collection.",
    "ncbi_link": "Sufu: 51684"
  },
  {
    "caption": "C. Detection of phosphorylated Sufu on S352/T353 after immunoprecipitation of HA-tagged Sufu WT and Sufu 351-353 AAA, as indicated.",
    "ncbi_link": "Sufu: 51684"
  },
  {
    "caption": "D. Detection of Myc-tagged Fbxl17 binding to Sufu full length (FL) or to the following Sufu peptides: Sufu 340-360(APSRKDSLESDSSTAIIPHEL); Sufu 340-360 [S352P/T353P] (phosphorylated on the residues S352 and T353); Sufu 351-372 (SSTAIIPHELIRTRQLESVHLK).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "E. Detection of HA-tagged Sufu binding to a Myc-tagged Fbxl17 construct encompassing the residues 318 to 701 (corresponding to the F-box motif and C-terminus region) assessed by in vitro binding assay. Both proteins were synthetized in vitro using a T7-coupled reticulocyte lysate system.",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "F. Detection of ubiquitylated Sufu immunoprecipitated from HEK293T cells co-transfected with HA-tagged ubiquitin (Ub), Myc-tagged Fbxl17 and Flag-tagged Gli1. MG132 (10µM) was added in all samples.",
    "ncbi_link": "Fbxl17: 64839
ubiquitin: 7314///7311///6233///7316"
  },
  {
    "caption": "A. Sufu protein levels in mouse embryonic fibroblasts (MEFs) Ptch1+/+, Ptch1+/- and Ptch1-/- transfected with a non-targeting siRNA (Control) or two siRNAs targeting mouse Fbxl17 (1) and (2).",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "B. Quantification of Fbxl17 mRNA levels in MEFs Ptch1+/+, Ptch1+/- and Ptch1-/- transfected as in A.",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "C. Analysis of Gli1 mRNA levels in MEFs Ptch1+/+ and Ptch1-/- upon Fbxl17 depletion using two different siRNAs. (mean ± SEM from 3 independent experiments, ***p<0.0005).",
    "ncbi_link": "Fbxl17: 50758
Gli1: 14632
Ptch1: 19206"
  },
  {
    "caption": "D. Analysis of Bcl2 mRNA levels in MEFs Ptch1+/+ and Ptch1-/- upon Fbxl17 depletion using two different siRNAs. (mean ± SEM from 3 independent experiments, **p<0.005; ***p<0.0005).",
    "ncbi_link": "Bcl2: 12043
Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "E. Detection of Flag-tagged Gli1 binding to HA-tagged Sufu in MEFs Ptch1-/- cells upon expression of Myc-tagged Fbxl17, or Fbxl17 depletion by two siRNAs. For each condition, 200 µg of whole cell lysate was immunoprecipitated.",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "F. Immunostaining of Fbxl17 using anti-Myc antibody in Ptch1-/- MEFs stably transduced with a pBABE vector expressing Fbxl17 tagged with Myc either at the N-terminus [Myc(N)-Fbxl17] or at the C-terminus [Myc(C)-Fbxl17]. Scale bars: 20 m.",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "G. Detection of Fbxl17 using anti-Myc antibody in Ptch1-/- MEFs stably expressing Myc(N)-Fbxl17 (Fbxl17 tagged at the N-terminus) and Myc(C)-Fbxl17 (Fbxl17 tagged at the C-terminus).",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "H. Detection of HA-tagged Fbxl17 binding to endogenous Sufu immunoprecipitated from cytoplasmic and nuclear extracts from Ptch1-/- MEFs. Asterisk (*) indicates a non specific band. Identification of cytoplasmic and nuclear fractions was performed by Lamin A/C and GAPDH detection.",
    "ncbi_link": "Fbxl17: 50758
Ptch1: 19206"
  },
  {
    "caption": "A. Cell proliferation of DAOY cells upon Fbxl17 depletion using a non-targeting siRNA (Control), two siRNAs against Fbxl17 (1) and (2) or upon reintroduction of a Myc-tagged Fbxl17 construct in Fbxl17-depleted DAOY cells using siRNA Fbxl17 (2) (mean ± SEM from 3 independent experiments, **p<0.005; ***p<0.0005).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "B. Quantification of Fbxl17 mRNA levels in DAOY cells transfected with a non-targeting siRNA (Control) or two siRNAs against Fbxl17 (1) and (2) (mean ± SEM from 3 independent experiments, **p<0.005).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "D. Cell proliferation of DAOY cells transfected with non-targeting siRNA (Control), siRNA against Fbxl17 or a combination of siRNA targeting Fbxl17 and Sufu. (mean ± SEM from 3 independent experiments, **p<0.005; ***p<0.0005).",
    "ncbi_link": "Fbxl17: 64839
Sufu: 51684"
  },
  {
    "caption": "E. Quantification of Fbxl17 mRNA levels in DAOY cells treated as in D mean ± SEM from 3 independent experiments, ***p<0.0005).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "A. Quantification of Fbxl17 mRNA levels in DAOY cells transfected with control shRNA or shRNA targeting Fbxl17. (mean ± SEM from 3 independent experiments, ***p<0.0005).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "B. Detection of Sufu protein levels in DAOY cells transfected with control shRNA or shRNA Fbxl17. Representative image of three independent experiments is shown.",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "C. Quantification of Gli1 mRNA levels in DAOY cells transfected with control shRNA or shRNA Fbxl17. (mean ± SEM from 3 independent experiments, **p<0.005).",
    "ncbi_link": "Fbxl17: 64839
Gli1: 2735"
  },
  {
    "caption": "D. T2- weighted magnetic resonance imaging (MRI) showing tumour development in rats injected with DAOY cells transfected with control shRNA or shRNA against Fbxl17. One representative image for each condition, at 10 weeks is shown. Scale bar: 5mm. E. Graph showing area of T2 hyperintensity (a surrogate marker of tumourgrowth) between 4 and 10 weeks post-tumour induction. Animals were injected with DAOY cells stably expressing control shRNA or shRNA against Fbxl17 (10,000 cells/1µL). (mean ± SEM; n = 5; two-way ANOVA, followed by unpaired t-test, *p<0.05, **p<0.01).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "F. Representative immunohistochemistry image of Vimentin staining. Scale bar: 1 mm.G. Quantification of tumour growth (vimentin staining) in rats injected with DAOY cells transfected with either control shRNA or shRNA against Fbxl17 (mean ± SEM; n = 5; unpaired t-test, *p<0.05).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "H. Representative immunohistochemistry image of Ki67 staining. Scale bar: 0.5 mm/0.1 mm.I. Quantification of proliferative index (Ki67 staining) in rats injected with DAOY cells transfected with either control shRNA or shRNA against Fbxl17 (mean ± SEM; n = 5; unpaired t-test, *p<0.05).",
    "ncbi_link": "Fbxl17: 64839"
  },
  {
    "caption": "A-C. mRNA expression of Sufu, Gli1 and Fbxl17 detected in 285 medulloblastoma samples (GEO accession: GSE37382), stratified by tumor subtype. Level of significance (p) for Kruskal-Wallis (KW) rank test is p<10-8. Analysis using one-way anova gave comparable results.",
    "ncbi_link": "Fbxl17: 64839
Gli1: 2735
Sufu: 51684"
  },
  {
    "caption": "D. Expression of Gli1 and Fbxl17 in the 285 patients is shown colored by subgroup; level of significance (p) for Kruskal-Wallis (KW) rank test is p<10-8, and Spearman's rank correlation (R=0.5640) is indicated.",
    "ncbi_link": "Fbxl17: 64839
Gli1: 2735"
  },
  {
    "caption": "E. Detection of HA-tagged Sufu wild type (WT) and HA-tagged Sufu S352F protein levels in NIH3T3 cells after cycloheximide (CHX) treatment. Where indicated, cells were transfected with a non- targeting siRNA (Control) or two siRNA to Fbxl17 (1) and (2).",
    "ncbi_link": "Fbxl17: 50758
Sufu: 24069"
  },
  {
    "caption": "F. Assessment of Hh pathway activation using Gli1-luciferase reporter assay in MEFs Sufu-/- upon reintroduction of HA-tagged Sufu WT or Sufu mutant S352F using a retroviral system. (mean ± SEM from 3 independent experiments, **p<0.005; ***p<0.0005).",
    "ncbi_link": "luciferase: 
Sufu: 24069"
  },
  {
    "caption": "C, D Effects of basic and bulky hydrophobic amino acids on LT-induced RFP-ASC specks formation in RAWRA cells. Fluorescence images were taken on a confocal microscopy (C). The percentages of cells showing RFP-ASC specks (mean values ± SD from three replicates) are in (D).",
    "ncbi_link": "RFP: 
ASC: 66824"
  },
  {
    "caption": "E Effects of basic and bulky hydrophobic amino acids on LT-induced caspase-1 activation in Tlr4-/- iBMDMs. Cells were treated as that in (A). Cell supernatants were subjected to anti-caspase-1 immunoblotting and the lysates were blotted with the anti-tubulin or anti-MEK3 antibody.",
    "ncbi_link": "Tlr4: 21898"
  },
  {
    "caption": "A RFP-ASC specks formation assay of the effect of Ubr2 knockdown on LT-induced inflammasome activation. RAWRA cells were transfected with a control siRNA or Ubr2-targeting siRNA mixtures for 60 h followed by LT treatment. The numbers in the merged panel are the percentages of the cells showing RFP-ASC specks.",
    "ncbi_link": "RFP: 
ASC: 66824
Ubr2: 224826"
  },
  {
    "caption": "B Effect of Ubr2 stable knockdown on caspase-1 activation in RAWRA cells. Cells stably expressing a control or Ubr2-targeting shRNA were incubated with WT LT (+) or its E687C mutant (-) for 3 h.",
    "ncbi_link": "Ubr2: 224826"
  },
  {
    "caption": "C Effects of Ubr2 knockdown (siRNA #05) on LT-induced NLRP1B inflammasome activation reconstituted in 293T cells. Cells were treated with WT LT (+) or its E687C mutant (-).",
    "ncbi_link": "Ubr2: 23304"
  },
  {
    "caption": "D, E Effect of Ubr2 knockout on NLRP1B or NAIP2-NLRC4 inflammasome activation. WT and Ubr2-/- iBMDMs were treated with LT or BsaK for 3 h. Cell viability was measured by using the ATP assay and data shown are mean values ± SD from three replicates (D).",
    "ncbi_link": "Ubr2: 224826"
  },
  {
    "caption": "Additional Ube2o siRNAs were used to confirm the inhibitory effect of Ube2o knockdown on LT-induced caspase-1 activation (C). Ube2o knockdown efficiency was measured by qPCR and are shown as mean values ± SD from three replicates.",
    "ncbi_link": "Ube2o: 217342"
  },
  {
    "caption": "RFP-ASC specks formation assay of the effect of Ube2o knockdown (siRNA Ube2o-01) on LT-induced inflammasome activation in RAWRA cells. The percentages of cells showing RFP-ASC specks (mean values ± SD from three replicates) are in (D).",
    "ncbi_link": "RFP: 
ASC: 66824
Ube2o: 217342"
  },
  {
    "caption": "F Co-immunoprecipitation interaction of UBE2O and UBR2. Myc-UBE2O and Flag-UBR2 were co-expressed in 293T cells and cell lysates were subjected to anti-Flag immunoprecipitation followed by immunoblotting analyses as shown.",
    "ncbi_link": "Flag: 
Myc: 
UBE2O: 
UBR2: 224826"
  },
  {
    "caption": "B Effect of LT treatment on NLRP1B protein level. 293T cells were transfected with Flag-NLRP1B expression plasmid for 24 h, and cells were then treated with WT LT (+) or its E687C mutant (-) for 4 h. Shown is the anti-Flag immunoblot of the total cell lysates.",
    "ncbi_link": "Flag: 
NLRP1B: 637515"
  },
  {
    "caption": "C RFP-ASC specks formation in 293T cells expressing an indicated NLRP1B variant. Cells were treated with LT for 3 h. Scale bar, 20 μm. 1-983 and 984-C (residues 984 to the C terminus) are the FIIND-mediated autocleaved fragments of NLRP1B.",
    "ncbi_link": "NLRP1B: 637515"
  },
  {
    "caption": "Effect of MG132 on LT-induced NLRP1B degradation. 293T cells expressing NLRP1B (1-983)-HA were treated with LT and MG132 for 8 h. Shown are the anti-HA and anti-tubulin immunoblots of the total cell lysates.",
    "ncbi_link": "NLRP1B: 637515"
  },
  {
    "caption": "E Effect of MG132 and Leu on LT-induced NLRP1B degradation. 293T cells expressing NLRP1B (1-983)-HA were treated with LT and MG132 for 8 h. 10 mM Leu was added to cells 30 min prior to LT treatment. Shown are the anti-HA and anti-tubulin immunoblots of the total cell lysates.",
    "ncbi_link": "HA: 
NLRP1B: 637515"
  },
  {
    "caption": "F LT-induced ubiquitination of NLRP1B. 293T cells expressing NLRP1B (1-983)-HA were treated with LT and/or MG132 for 6 h. Cells were then harvested for anti-HA immunoprecipitation and subjected to immunoblotting analyses using indicated antibodies.",
    "ncbi_link": "HA: 
NLRP1B: 637515"
  },
  {
    "caption": "(A) In situ proximity ligation assay (PLA) of ZEB1 with JUN, FOSL1 and TAZ shows close proximity of ZEB1 with JUN and FOSL1 but not TAZ in the nucleus of MDA-MB-231 cells indicated by red fluorescent dots. As negative control ZEB1 was transiently knocked down by siRNA. In the left panel representative microscopic images are shown. Scale bar = 20 µm. Quantification of the PLA is shown on the right.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(A) Definition of two different ZEB1 peak subsets based on the presence or absence of overlapping YAP and JUN peaks. The two illustrative genome browser images show one example of a ZEB1-only peak and one example of a ZEB1/YAP/JUN peak (at the EFEMP1 gene and within the SHROOM3 gene, respectively). Control (ctrl) is the input for ZEB1 and IgG for the YAP and JUN ChIP-seqs. ChIP-seqs and respective controls were scaled accordingly.",
    "ncbi_link": "EFEMP1: 2202
SHROOM3: 57619"
  },
  {
    "caption": "(A) qRT-PCR in TGFß treated MCF10A cells after siRNA mediated knockdown of ZEB1, FOSL1 or YAP compared to control knockdown cells. Knockdown efficiency of all three factors is shown on the left. The right panel shows their effects on 11 ZEB1/YAP/AP-1 activated target genes.",
    "ncbi_link": "TGFß: 
FOSL1: 8061
AP-1: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(B) Overlap of ZEB1, YAP and JUN peaks at the promoter of CYR61, CTGF and ANKRD1 and in a known enhancer region of the DOCK9 gene.",
    "ncbi_link": "ANKRD1: 27063
CYR61: 3491
CTGF: 1490
DOCK9: 23348"
  },
  {
    "caption": "(C) ZEB1-only peak at the promoter of LLGL2, a well-known ZEB1 repressed target.",
    "ncbi_link": "LLGL2: 3993"
  },
  {
    "caption": "(D) Luciferase reporter assay in MDA-MB-231 cells comparing control and transient siRNA-mediated knockdown of ZEB1. Reporter constructs of regulatory regions of genes For reporter assays, firefly luciferase activity was normalized to co-transfected renilla luciferase.",
    "ncbi_link": "luciferase: 
ZEB1: 6935"
  },
  {
    "caption": "(E) Luciferase reporter assays with the ANKRD1 promoter and DOCK9 enhancer constructs in MCF7 cells upon overexpression of ZEB1, YAP and JUN/FOSL1 (AP-1) or different combinations of the factors. n = 5 (ANKRD1) and n = 3 (DOCK9); shown is mean ± s.e.m.; *P ≤ 0.05; ratio paired t-test. For reporter assays, firefly luciferase activity was normalized to co-transfected renilla luciferase.",
    "ncbi_link": "luciferase: 
ANKRD1: 27063
DOCK9: 23348
FOSL1: 8061
AP-1: 3725
JUN: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(C) The upper panel shows a schematic representation of the ANKRD1 luciferase reporter constructs. The lower panel shows luciferase reporter assays with these different ANKRD1 promoter constructs in MCF7 cells upon overexpression of ZEB1, YAP and JUN/FOSL1 or different combinations of the factors. n = 4-5; shown is mean ± s.e.m.; *P ≤ 0.05; **P ≤ 0.01; ratio paired t-test. Firefly luciferase activity was normalized to co-transfected renilla luciferase.",
    "ncbi_link": "luciferase: 
ANKRD1: 27063
FOSL1: 8061
JUN: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(D) Left panel: EMSA using nuclear extracts from MDA-MB-231 and labelled TEAD binding side as probe (black arrow). Competition of specific binding complex (read arrow) with cold probe (c), anti-JUN, -panTEAD, and -ZEB1 antisera. Right panel: recombinant GST-ZEB1, but not GST-Ctrl, only binds to Z-box.",
    "ncbi_link": "GST: 
ZEB1: "
  },
  {
    "caption": "(B) Comparison of ZEB1 ChIP-seq peaks with ZEB1-dependent changes in chromatin activation status identified by ATAC-seq on control and ZEB1 knock-down MDA-MB-231 cells. Percentage of ZEB1-only (n=5,963) and ZEB1/YAP/JUN peaks (n=1,993) falling into ZEB1 repressed or activated genomic regions are shown.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "(C) Genome browser tracks of ZEB1, YAP and JUN ChIP-seq signal intensity in wild type cells overlaid to ATAC-seq signal intensity in wild type, control (shCtrl) and ZEB1 (shZEB1) knock-down MDA-MB-231 cells. One known ZEB1 repressed target (CDH1) and one activated target (ANKRD1) are shown.",
    "ncbi_link": "ANKRD1: 27063
CDH1: 999
ZEB1: 6935"
  },
  {
    "caption": "(A) Correlation of ZEB1 mRNA expression with the expression of YAP, FOSL1 and JUN across all breast cancer cell lines included in the cancer cell line encyclopedia (CCLE). rs: Spearman's rank correlation coefficient.",
    "ncbi_link": "FOSL1: 8061
JUN: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(C) Heatmap of mRNA expression data of ZEB1, YAP, JUN and 9 selected activated ZEB1/YAP/AP-1 target genes in breast cancer patient samples (GSE18229). Genes were selected for known roles in tumour promoting properties like cell migration. Tumours in which ≥ 6 out of 9 genes of the selected ZEB1/YAP/AP-1 target gene set were expressed higher than the 60th percentile of expression were defined as "tumour promoting gene set high"; when expression of ≥ 6 out of the 9 genes was below the 40th percentile, tumours were defined as "tumour promoting gene set low". Tumours were annotated according to their molecular subtype.",
    "ncbi_link": "AP-1: 3725
JUN: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(E) Kaplan Meier plots from survival analyses of human breast cancers patient samples (GSE18229) showing relapse free survival (RFS) based on the combined expression of the 9 selected ZEB1/YAP/AP-1 activated targets HR: hazard ratio. p-value from log-rank test. (F) Kaplan Meier plots from survival analyses of human ER-/PR- breast cancers showing distant metastasis free survival (DMFS) based on the combined expression of the 9 selected ZEB1/YAP/AP-1 activated targets HR: hazard ratio. p-value from log-rank test.",
    "ncbi_link": "AP-1: 3725
YAP: 10413
ZEB1: 6935"
  },
  {
    "caption": "(A) TNF concentrations in supernatants of WT and Tnf-/- BMDMs unstimulated or stimulated with 10 ng/ml Pam3CSK4, quantified by ELISA. (Left) 0 h, 4 h and 8 h time points. (Right) Close-up of 0 h time point. Dashed line indicates mean of blank measurements. Data are represented as mean ± SD of 3 (4 h, 8 h) or 5 (0 h) biological replicates using cells from 2 (4 h, 8 h) or 3 (0 h) mice. Statistical significance was determined by two-tailed paired-sample t-test.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(E - J) Nuclear localization of mVenus-RelA upon stimulation with 10 ng/ml TNF (E - G) or 10 ng/ml Pam3CSK4 (H - J), measured over time in WT and Tnf-/- BMDMs by fluorescence microscopy and quantified by automated image analysis. (E, H) Each row of the heatmap represents the NFκB signaling trajectory of one cell. Trajectories are sorted by maximum amplitude. Example trajectories are shown below. Data from a single representative experiment is depicted. (F, I) Indicated dynamic features were calculated from signaling trajectories. Violin plots depict pooled data from 8 (F) or 6 (I) biological replicates (total # of cells: 5769/5238 (F), 3843/3899 (I)). Marker indicates median of distribution. Statistical significance was determined by Wilcoxon rank sum test. Number indicates log10(p-value). (G, J) Percentage of cells with NFκB trajectories categorized as oscillatory based on a frequency threshold among all responder cells in each experiment. Data are represented as mean ± SD of 8 (G) or 6 (J) biological replicates. Statistical significance was determined by two-tailed paired-sample t-test. (F, G) Some replicates for Tnf-/- BMDMs overlap with data",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(B) IκBα mRNA expression in WT and Tnf-/- BMDMs stimulated with 10 ng/ml TNF over 2 h, determined by RT-qPCR. IκBα expression was normalized to GAPDH expression and then to maximum WT value in each time course replicate. Data are represented as mean ± SD of 5 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point. Some replicates for Tnf-/- BMDMs overlap with data",
    "ncbi_link": "GAPDH: 14433
IκBα: 18035
Tnf: 21926"
  },
  {
    "caption": "Phosphorylation of IKK, JNK, ERK, and p38 and total IKK levels in WT and Tnf-/- BMDMs stimulated with 10 ng/ml TNF over 2 h, determined by SDS-PAGE followed by Western Blotting. (C) One of three representative experiments is shown. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "Phosphorylation of IKK levels in WT and Tnf-/- BMDMs stimulated with 10 ng/ml TNF over 2 h For quantification of p-IKK (D) levels, basal levels (0 min) were deducted per genotype before normalizing to maximum WT value in each experiment. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "Phosphorylation of JNK levels in WT and Tnf-/- BMDMs stimulated with 10 ng/ml TNF over 2 h, p-JNK (E) levels, basal levels (0 min) were deducted per genotype before normalizing to maximum WT value in each experiment. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(E) TNF receptor 1 (TNFR1, left), TNF receptor 2 (TNFR2, center), and CD11b (right) cell surface expression in Tnf-/- compared to WT BMDMs unstimulated or stimulated for 30 min with 10 ng/ml TNF, measured by flow cytometry. Per experiment, median fluorescence intensity average of 3 culture replicates in Tnf-/- cells is expressed as percent of expression in WT cells. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed one-sample t-test using a hypothesis mean of 100.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(F) (Left) TNF receptor 1 (TNFR1) cell surface expression at baseline in BMDMs pre-treated with TNFR1 siRNA, control (ctrl) siRNA, or untreated (-). Median fluorescence intensity is expressed as percent of expression in untreated WT cells. (Right) Percentage of cells with oscillatory NFκB activity (measured by fluorescence microscopy) among all responder cells upon indicated siRNA pre-treatment and stimulation with 10 ng/ml TNF. Per condition, 1032 - 1484 responding cells were analyzed. (Left, right) Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by one-tailed paired-sample t-test.",
    "ncbi_link": "TNFR1: 21938"
  },
  {
    "caption": "(D) IκBα mRNA expression in Tnf-/- and Tnf-/-p100-/- BMDMs stimulated with 10 ng/ml TNF over 2 h, determined by RT-qPCR. IκBα expression was normalized to GAPDH expression and then to maximum WT value also obtained with each replicate. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point. Data for Tnf-/- BMDMs is also included",
    "ncbi_link": "GAPDH: 14433
p100: 18034
IκBα: 18035
Tnf: 21926"
  },
  {
    "caption": "(E) Levels of nuclear NFκB DNA binding activity in Tnf-/- and Tnf-/-p100-/- BMDMs stimulated with 10 ng/ml TNF over 2 h, determined by EMSA. Quantification of the NFκB-DNA complex was normalized to the quantified NFY-DNA complex, and then to maximum WT value also obtained with each replicate. Data are represented as mean ± SD of 3 biological replicates. Statistical significance was determined by two-tailed paired-sample t-test for each time point. Data for Tnf-/- BMDMs is also shown",
    "ncbi_link": "p100: 18034
Tnf: 21926"
  },
  {
    "caption": "(F - H) Nuclear localization of mVenus-RelA upon stimulation with 10 ng/ml TNF was measured over time by fluorescence microscopy in Tnf-/- and Tnf-/-p100-/- BMDMs and quantified by automated image analysis. (F) Each row of the heatmap represents the NFκB signaling trajectory of one cell. Trajectories are sorted by maximum amplitude. Example trajectories are shown below. Data from a single representative experiment are depicted. (G) Indicated dynamic features were calculated from signaling trajectories. Violin plots depict pooled data from 6 biological replicates (total # of cells: 4030/4133). Marker indicates median of distribution. Statistical significance was determined by Wilcoxon rank sum test. Number indicates log10(p-value). (H) Percentage of cells with NFκB trajectories categorized as oscillatory based on a frequency threshold among all responder cells in each experiment. Data are represented as mean ± SD of 6 biological replicates. Statistical significance was determined by one-tailed paired-sample t-test. (G, H) Data for Tnf-/- BMDMs is also included",
    "ncbi_link": "p100: 18034
Tnf: 21926"
  },
  {
    "caption": "(E) Volcano plot of single-cell gene expression in Tnf-/- vs. WT BMDMs upon TNF stimulation. Dashed lines indicate p-value threshold of 0.01 and absolute log2(FC) threshold of 0.5. Only genes induced by P3C4 or TNF stimulation over mock in WT cells are included (p-value threshold of 0.05 and log2(FC) threshold of 0.25).",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(F) Violin plots of single-cell gene expression in WT and Tnf-/- BMDMs upon mock, TNF, or Pam3CSK4 stimulation. The 10 genes shown are significantly upregulated in Tnf-/- vs. WT cells upon TNF stimulation (see (E)).",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(D) Violin plot of log­2(FC) of normalized H3K4me1 ChIP-seq signal in TNF- or Pam3CSK4-stimulated over unstimulated WT or Tnf-/- BMDMs within Cluster 1 regions (533 regions). Statistical significance was determined by Kolmogorov-Smirnov test. Data are represented as mean of two biological replicates for each genomic region. In the boxplot, central band indicates the median, boxes the interquartile range (IQR), whiskers values within 1.5 IQR from the median.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(E) Examples of genomic regions with differential H3K4me1 signal in TNF stimulation in Cluster 1. Tracks for WT and Tnf-/- BMDMs unstimulated or stimulated with TNF or Pam3CSK4 in two biological replicates (R1, R2) are shown.",
    "ncbi_link": "Tnf: 21926"
  },
  {
    "caption": "(A-B) Intraphagosomal proteolysis and acidification assays show that loss of RNF115 increases phagosome maturation in BMA cells. (C) Complementing the RNF115 KO with WT RNF115 or a W259A mutant which is unable to bind to E2 enzymes, shows that RNF115 ligase activity is required for the increase of phagosome maturation.",
    "ncbi_link": "RNF115: 67845"
  },
  {
    "caption": "(C) Immunofluorescence micrographs of VAMP8 (green) and Syntaxin-7 (STX7; red) show strong colocation around 3 µm silica bead phagosomes (white) in BMA macrophages. Nuclei are stained with Dapi. Scale bar is 5 µm. To account for people with red-green colour-blindness, (D) Colocation of VAMP8 (green) and STX7 (red) on individual phagosomes between WT and RNF115 KO cells represented by intersection, Manders' M1 and overlap coefficients. Data is represented as a box and whisker plot of total values across biological duplicate experiments, where the whiskers represent the minimum to maximum values and the central band indicates the median.",
    "ncbi_link": "RNF115: 67845"
  },
  {
    "caption": "(D) Box and whisker plot represents the quantification of the percentage (%) of the hepatic lesion area in the livers from six wild-type (WT) and six RNF115 KO (KO) mice after 48 h infection with S. aureus. Haematoxylin and eosin (H&E)-stained liver sections of one representative animal per genotype are shown on the right, dotted line depicts the damaged area.",
    "ncbi_link": "RNF115: 67845"
  },
  {
    "caption": "(E-F) Box and whisker plots represent the average cell counts per high power field (HPF) of CD3 positive T-cells (E), and CD68 positive macrophages (F) in the livers from six wild-type (WT) and six RNF115 KO (KO) mice after 48 h infection with S. aureus. Representative immunohistochemistry sections are shown on the right.",
    "ncbi_link": "RNF115: 67845"
  },
  {
    "caption": "A, B Representative transmission electron microscopy (TEM) images showing keratinocyte mitochondria (red arrow) in patient 1 (A) and in the Mbtps1-conditional knockout (cKO) mouse model (B). Scale bars: 2 µm.",
    "ncbi_link": "Mbtps1: 56453"
  },
  {
    "caption": "C, D Quantification of the mitochondrial number and morphology in patient 1 (C) and the Mbtps1-cKO mouse model (D). (C) Left panel: n = 13 biological replicates of normal individuals, n = 10 biological replicates of patient 1. Middle and right panel: n = 121 biological samples of normal individuals and patient 1. (D) Left panel: n = 23 biological replicates of Mbtps1-loxP mice; n = 15 biological replicates of Mbtps1-cKO mice. Middle panel and right panel: n =113 biological replicates of Mbtps1-loxP mice and Mbtps1-cKO.",
    "ncbi_link": "Mbtps1: 56453"
  },
  {
    "caption": "E Immunofluorescence experiments showed that mutant S1P (p.Val355Gly and p.Ter1053Arg) was diffusely localized in the cytosol and showed lower mitochondrial localization compared with wild-type S1P, which suggested that these variants disrupt its mitochondrial import. The white arrowheads indicate the colocation (yellow) of S1P (green) and the mitochondrial tracer (red). Scale bars: 20 μm (panels 1-4); scale bars: 2 μm (panel 5).",
    "ncbi_link": "S1P: 8720"
  },
  {
    "caption": "G A component separation assay revealed a lower expression of mutant S1P (p.Val355Gly and p.Ter1053Arg) than wild-type S1P in mitochondria.",
    "ncbi_link": "S1P: 8720"
  },
  {
    "caption": "H The impaired binding of mutant S1P (p.Val355Gly and p.Ter1053Arg) to translocase of the outer membrane (TOM) 70 and translocase of the inner membrane (TIM) 23 was detected by a coimmunoprecipitation (Co-IP) assay.",
    "ncbi_link": "S1P: 8720"
  },
  {
    "caption": "B Unchanged mRNA levels and decreased protein levels of ETFA and ETFB were observed in the skin biopsy of patient 1. Quantitative RT-PCR analysis (upper panel, n = 6 biological replicates of normal controls; n = 6 technical replicates of patient 1) and immunohistochemistry (lower panel, n = 6 biological replicates; n = 3 technical replicates) of the S1P, ETFA and ETFB levels.",
    "ncbi_link": "ETFA: 2108
ETFB: 2109"
  },
  {
    "caption": "C Representative immunohistochemistry images of S1P, ETFA and ETFB in both Mbtps1-conditional knockout (cKO) and Mbtps1-loxP mice. Scale bars: 100 μm.",
    "ncbi_link": "Mbtps1: 56453"
  },
  {
    "caption": "D MBTPS1 gene knockout led to decreases in the ETFA and ETFB protein levels in vivo. Quantitative RT-PCR analysis (upper panel, n = 6 biological replicates) and immunohistochemistry (lower panel, n = 6 biological replicates) of the S1P, ETFA and ETFB levels in Mbtps1-cKO mice and Mbtps1-loxP mice.",
    "ncbi_link": "ETFA: 110842
ETFB: 110826
Mbtps1: 56453
MBTPS1: 56453"
  },
  {
    "caption": "E Cycloheximide (CHX) chase analysis showed that MBTPS1 knockout induced rapid degradation of ETFA and ETFB proteins in HaCaT cells. Left panel: Representative western blotting images of the ETFA and ETFB protein levels during CHX chase. Right panel: Quantification of the immunoblotting results corresponding to the left panel (n = 3 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "F Mutant S1P (p.Val355Gly and p.Ter1053Arg) only weakly interacted with ETFA and ETFB. We constructed Flag-tagged wild-type and mutant S1P HaCaT cell lines and then performed a Co-IP assay with Flag antibody, and the interaction between S1P and ETFA/ETFB was detected by immunoblotting.",
    "ncbi_link": "S1P: 8720"
  },
  {
    "caption": "G Wild-type S1P, but not mutant S1P (p.Val355Gly and p.Ter1053Arg), decreased the association between ETFA and ETFB. We performed a Co-IP assay with an ETFA antibody, and the interaction between ETFA and ETFB was detected by immunoblotting.",
    "ncbi_link": "S1P: 8720"
  },
  {
    "caption": "Mitochondrial respiration (OCR) in control (Ctrl) and MBTPS1-knockout (KO) HaCaT cells was quantified in real time using a Seahorse extracellular flux analyser. Right subpanels: Quantification of basal respiration, maximal respiration, and OCR-coupled ATP production in mitochondrial respiration (n = 5 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "B Quantification of relevant metabolites in mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis in Ctrl and MBTPS1-KO HaCaT cells (n = 4 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "C Nonmitochondrial respiration (ECAR) was quantified in real time using a Seahorse extracellular flux analyser. Quantification of non-glycolytic acidification, glycolysis, glycolytic capacity, and glycolytic reserve in Ctrl and MBTPS1-KO HaCaT cells (n = 4 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "D MBTPS1 knockout led to a decrease in global ATP production in HaCaT cells. Control and MBTPS1-KO HaCaT cells were cultured in 6-well dishes. A standard curve was generated to calculate the sample ATP concentrations using an ATP Lite Luminescence Assay Kit (n = 4 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "E MBTPS1 knockout significantly increased the generation of mitochondrial reactive oxygen species (Mito SOX) in HaCaT cells. Left panel: Representative immunofluorescence images of Mito SOX in HaCaT cells. Scale bars: 100 µm. Right panel: The immunofluorescence intensity was quantified to calculate the relative Mito ROS level in HaCaT cells (n = 4 biological replicates).",
    "ncbi_link": "MBTPS1: 8720"
  },
  {
    "caption": "A The S1P deficiency-induced decrease in ETFA and ETFB was significantly reversed by riboflavin (Rib) in a concentration-dependent manner in MBTPS1-KO HaCaT cells. GAPDH was used as a loading control. MBTPS1-KO cells were initially cultured in DMEM for 24 h and supplemented with 0, 2.5, 5, or 10 µM riboflavin for 3 days. The expression of ETFA and ETFB was then detected by immunoblotting.",
    "ncbi_link": "MBTPS1: 8720
S1P: 8720"
  },
  {
    "caption": "B The S1P deficiency-induced abnormalities in mitochondrial respiration can be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT cells. Left panel: Mitochondrial respiration (OCR) was quantified in real time using a Seahorse extracellular flux analyser.",
    "ncbi_link": "ETFA: 2108
S1P: 8720"
  },
  {
    "caption": "C The decreased global ATP production caused by S1P deficiency could be significantly reversed by riboflavin supplementation and ETFA/B overexpression in HaCaT cells (n = 4 biological replicates).",
    "ncbi_link": "ETFA: 2108
S1P: 8720"
  },
  {
    "caption": "(A) H1299 cells were transfected with Myc-β-catenin, CK1α and MDMX mutants. Phosphorylation of β-catenin S45 was determined by western blot. Co-expression of MDMX blocked the increase of pS45 level. MDMXSG (W200S/W201G) and MDMX-1-300 were defective for CK1α binding.",
    "ncbi_link": "Myc: 
CK1α: 1452
β-catenin: 1499
MDMX: 4194"
  },
  {
    "caption": "(A, B) H1299 cells and human foreskin fibroblasts HFF were stably infected with lentivirus expressing MDMX and analyzed by western blot.",
    "ncbi_link": "MDMX: 4194"
  },
  {
    "caption": "(C) H1299 cells were transiently transfected with CK1α plasmid and analyzed for β-catenin phosphorylation by western blot.",
    "ncbi_link": "CK1α: 1452"
  },
  {
    "caption": "(D) Cytoplasmic and nuclear fractions of H1299 cells stably expressing MDMX were analyzed for indicated markers.",
    "ncbi_link": "MDMX: 4194"
  },
  {
    "caption": "(E) Extract of H1299 expressing MDMX at indicated amounts were analyzed for β-catenin S45 kinase activity in a titration assay.",
    "ncbi_link": "MDMX: 4194"
  },
  {
    "caption": "(F) Extracts of H1299 cells separately transfected with MDMX or CK1α were mixed in the presence of CK1α inhibitors. In vitro formation of MDMX-CK1α complex was detected by MDMX IP followed by CK1α western blot.",
    "ncbi_link": "CK1α: 1452
MDMX: 4194"
  },
  {
    "caption": "(A, B, C, D) Cells were treated with MDMX siRNA for 48 hrs and analyzed for β-catenin pS45 level by western blot.",
    "ncbi_link": "MDMX: 4194"
  },
  {
    "caption": "(C) H1299 cells were cotransfected with MDMX, CK1α and p53 mutants. MDMX-CK1α binding was determined by IP-western blot.",
    "ncbi_link": "CK1α: 1452
MDMX: 4194
p53: 7157"
  },
  {
    "caption": "(D) Endogenous p53 in A549 (wt) and Panc1 (R273H) cells were depleted by CRISPR/Cas9 knockout. β-catenin pS45 level was determined by western blot.",
    "ncbi_link": "Cas9: 
CRISPR: 
p53: 7157"
  },
  {
    "caption": "(A) H1299 cells were transfected with MDMX and CK1α mutants. MDMX-CK1α binding was determined by IP-western blot.",
    "ncbi_link": "CK1α: 1452
MDMX: 4194"
  },
  {
    "caption": "(A) MEF cell lines derived from 3 p53-/-;MDMXSG/SG and 3 p53-/-;MDMXwt/wt embryos were analyzed for β-catenin pS45 level by western blot.",
    "ncbi_link": "MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(C) Volcano plot of differential gene expression between p53-/-;MDMXSG/SG and p53-/-;MDMXwt/wt MEF lines.",
    "ncbi_link": "MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(D) Multiple Wnt signaling genes were down regulated in p53-/-;MDMXSG/SG MEF cell lines.",
    "ncbi_link": "MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(E) RT-PCR confirmation of Wnt pathway genes down-regulated in p53-/-;MDMXSG/SG MEF (average of 3 cell lines, mean +/- SD) and thymus from 1 month old mice (average of 3 mice, mean +/- SD). **p<0.01, *p<0.05 (Student's t test).",
    "ncbi_link": "MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(F) p53-/-;MDMXSG/SG and p53-/-;MDMXwt/wt cells were treated with conditioned medium containing Wnt3a. Axin2 mRNA level was determined by RT-PCR (average of 3 experiments, mean +/- SD). *p<0.05 (Student's t test).",
    "ncbi_link": "Axin2: 12006
MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(C) Survival curves of p53-/-;MDMXSG/SG and p53-/-;MDMXwt/wt mice. Thymic lymphomas were the major cause of mortality in both genotypes.",
    "ncbi_link": "MDMX: 17248
p53: 22059"
  },
  {
    "caption": "(D) SVA reporter repression with the same set of mutants as in (B). Data were normalized to KAP1 KO cells transfected with an empty vector (EV).",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "H. Immunoblot analysis of Arg1 and tubulin levels in lysates from non-infected (ni) and infected wild-type and stat6-/- iBMDMs for 60 or 120 min.",
    "ncbi_link": "stat6: 20852"
  },
  {
    "caption": "D. Immunofluorescence confocal microscopy of the colocalization of Kp52145 harbouring pFPV25.1Cm, and cresyl violet dye in wild-type (WT) and stat6-/- macrophages. The images were taken 90 min post infection. Images are representative of duplicate coverslips of three independent experiments. E. Percentage of Kp52145 harbouring pFPV25.1Cm co-localization with cresyl violet over a time course. Values are given as mean percentage of Kp52145 co-localizing with the marker ± SEM. The number of infected cells counted per time in three independent experiments are indicated in the figure.",
    "ncbi_link": "stat6: 20852"
  },
  {
    "caption": "A. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), tlr2-/-, tlr4-/- and tlr2/4-/- iBMDMs for 60 or 120 min. B. Immunoblot analysis of Arg1and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), tlr2-/-, tlr4-/- and tlr2/4-/- iBMDMs for 60 or 120 min.",
    "ncbi_link": "tlr2: 7097
tlr2: 24088
tlr4: 21898"
  },
  {
    "caption": "F. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), myd88-/-, tram/trif-/- for 60 or 120 min. G. Immunoblot analysis of Arg1 and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), myd88-/-, tram/trif-/- for 60 or 120 min.",
    "ncbi_link": "myd88: 17874
tram: 225471
trif: 225471"
  },
  {
    "caption": "A. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or ifnar1-/- for 60 or 120 min. B. Immunoblot analysis of Arg1 and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or ifnar1-/- for 60 or 120 min.",
    "ncbi_link": "ifnar1: 15975"
  },
  {
    "caption": "K. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or irf3-/- for 60 or 120 min. L Immunoblot analysis of Arg1 and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or irf31-/- for 60 or 120 min.",
    "ncbi_link": "irf3: 54131"
  },
  {
    "caption": "A. Immunoblot analysis of phospho-CREB (pCREB) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or tlr4-/- for 60 or 120 min. B. Immunoblot analysis of phospho-CREB (pCREB) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or myd88-/- for 60 or 120 min.",
    "ncbi_link": "myd88: 17874
tlr4: 21898"
  },
  {
    "caption": "D. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or il10-/- for 60 or 120 min.",
    "ncbi_link": "il10: 16153"
  },
  {
    "caption": "F. Immunoblot analysis of Arg1 and tubulin levels in lysates from non-infected (ni) and infected wild-type (WT), or il10-/- for 60 or 120 min.",
    "ncbi_link": "il10: 16153"
  },
  {
    "caption": "L. Immunofluorescence confocal microscopy of the colocalization of Kp52145 harbouring pFPV25.1Cm, and cresyl violet dye in wild-type (WT) and il10-/- macrophages. The images were taken 90 min post infection. Images are representative of duplicate coverslips of three independent experiments. M. Percentage of Kp52145 harbouring pFPV25.1Cm co-localization with cresyl violet over a time course in wild-type (WT) and il10-/- macrophages. Values are given as mean percentage of Kp52145 co-localizing with the marker ± SEM. The number of infected cells counted per time in three independent experiments are indicated in the figure.",
    "ncbi_link": "il10: 16153"
  },
  {
    "caption": "A. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from wild-type macrophages non-infected (ni), or infected with Kp52145 or the LPS O-polysaccharide mutant, strain 52145-Δglf, for 60 or 120 min.",
    "ncbi_link": "glf: "
  },
  {
    "caption": "C. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from wild-type macrophages non-infected (ni), or infected with Kp52145 or the CPS mutant, strain 52145-ΔwcaK2, for 60 or 120 min.",
    "ncbi_link": "wca: "
  },
  {
    "caption": "A. arg1 mRNA levels were assessed by qPCR in hM-CSF-treated PBMCs from 6 donors non-infected (ni) or infected Kp52145 for 1, 3 or 5 h. D. ido mRNA levels were assessed by qPCR in hM-CSF-treated PBMCs from 6 donors non-infected (ni) or infected Kp52145 for 1, 3 or 5 h.",
    "ncbi_link": "arg1: 383
ido: 169355///3620"
  },
  {
    "caption": "B. il10 mRNA levels were assessed by qPCR in M-CSF-treated PBMCs from 6 donors non-infected (ni) or infected Kp52145 for 1, 3 or 5 h. C. chi3l mRNA levels were assessed by qPCR in hM-CSF-treated PBMCs from 6 donors non-infected (ni) or infected Kp52145 for 1, 3 or 5 h.",
    "ncbi_link": "chi3l: 12655
il10: 3586"
  },
  {
    "caption": "O. Immunoblot analysis of phospho-STAT6 (pSTAT6) and tubulin levels in lysates from PMA-treated THP-1 macrophages non-infected (ni), or infected with Kp52145 or the CPS mutant, strain 52145-ΔwcaK2, for 60 or 120 min.",
    "ncbi_link": "wca: "
  },
  {
    "caption": "E) and F) Competition assay in HeLa cells stably expressing RFP-tagged B56 inhibitor (LxxIxE) or control inhibitor (AxxAxA). YFP-B56α was transfected into and subsequently purified from these cell lines. Loss of binding of indicated proteins determined by either mass spectrometry (pink - B56 SLIM containing protein and known B56 interactor; blue - known B56 interactor, green - B56 SLIM containing protein) (E) or Western blotting (F).",
    "ncbi_link": "YFP: 
B56α: 5525"
  },
  {
    "caption": "B) The indicated YFP-FoxO3 constructs were transfected into HeLa cells, purified using YFP resin and PP2A-B56 binding determined by Western blotting. PP2A-A; scaffold subunit.",
    "ncbi_link": "YFP: 
FoxO3: 2309"
  },
  {
    "caption": "C) - D) YFP-FoxO3 constructs were transfected into HeLa cells and lysates (pS413) or YFP purifications (pS253) were subjected to Western Blotting and probed with the indicated phosphoantibodies. Quantifications arise from five (pS413) or three (pS253) independent experiments. Mean and standard deviation shown in plots as black bars.",
    "ncbi_link": "YFP: 
FoxO3: 2309"
  },
  {
    "caption": "C) The indicated full-length murine Myc-ADAM17 derivatives were transfected into HeLa cells stably expressing YFP-B56α. YFP-B56α was purified (IP) and ADAM17 binding determined by Western blotting. PP2A-C; catalytic subunit, PP2A-A; scaffold subunit.",
    "ncbi_link": "Myc: 
YFP: 
ADAM17: 11491
B56α: 5525"
  },
  {
    "caption": "D) Dephosphorylation by the PP2A-B56α holoenzyme complex of the indicated phosphorylated GST-ADAM17 (V724-C827) fragments. The GST-ADAM17 (V724-C827) substrates was phosphorylated with radioactive ATP using Protein Kinase A and incubated with the PP2A-B56α holoenzyme. Removal of radioactive phosphate was monitored over time. The mean and Standard deviation of 4 independent experiments are shown.",
    "ncbi_link": "ADAM17: 11491"
  },
  {
    "caption": "E) Protein expression of ADAM17 variants in the DLD-1 Adam17-/- cell line, determined by Western blot. GAPDH was used as an internal loading control.",
    "ncbi_link": "Adam17: 6868"
  },
  {
    "caption": "F) Amphiregulin (AREG) shedding measured by ELISA of conditioned media from untreated, H2O2 treated or irradiated with x-ray DLD-1 Adam17-/- cells (clone #1) expressing full-length ADAM17 variants (wt, I762A or LEE). Two sided, unpaired Students t-test test was applied to test for significant differences *p<0.05, **p<0.01, ***p<0.001. Mean and standard deviation indicated from at least three independent experiments.",
    "ncbi_link": "Adam17: 6868
ADAM17: 11491"
  },
  {
    "caption": "G) Exogenous wt and I762A full length ADAM17 was immuno-purified from Adam17-/- cells treated with H2O2 and subjected to label-free LC-MS/MS to determine differential phosphorylation status of T735 and S808 (S811 in murine ADAM17).",
    "ncbi_link": "Adam17: 6868
ADAM17: 11491"
  },
  {
    "caption": "A) EGFR activation in the ADAM17 variant expressing DLD-1 Adam17-/- cells upon H2O2 treatment, determined by Western blot and quantified below as the ratio of EGFR autophosphorylated at Tyr1068 to total EGFR. Two sided, unpaired Students t-test test was applied to test for significant differences *p<0.05, **p<0.01. Mean and standard deviation indicated from three independent experiments.",
    "ncbi_link": "Adam17: 6868"
  },
  {
    "caption": "(B, C) B) Cell proliferation and C) Matrigel invasion of the ADAM17 variant expressing DLD-1 Adam17-/- cells. Two sided, unpaired Students t-test test was applied to test for significant differences *p<0.05, **p<0.01. Mean and standard deviation indicated from three independent experiments.",
    "ncbi_link": "ADAM17: 11491
Adam17: 6868"
  },
  {
    "caption": "D) Protein expression of the ADAM17 variants in the mouse breast cancer cell line 4T1 Adam17-/-, determined by Western blot. GAPDH was used as an internal loading control.",
    "ncbi_link": "Adam17: 11491"
  },
  {
    "caption": "E) Average tumor volume ± SEM of 4T1 Adam17-/- cells expressing the ADAM17 variants injected into the mammary fat pad of Balb/c mice (n=10 for each group). Indicated significances are between the I762A and LEE tumors. Two sided, unpaired Students t-test test was applied to test for significant differences *p<0.05. Mean and standard error of the mean indicated.",
    "ncbi_link": "Adam17: 11491
ADAM17: 11491"
  },
  {
    "caption": "F) Survival curve of the tumor bearing mice injected with 4T1 Adam17-/- cells expressing the ADAM17 variants (n=10 for each group). The indicated significances are between the LEE and wt tumor bearing mice, and the LEE and I762A tumor bearing mice. Log-rank test was applied to test for significant differences. *p<0.05.",
    "ncbi_link": "Adam17: 11491
ADAM17: 11491"
  },
  {
    "caption": "IFN-β promoter activity (A) in Myc empty vector (200 ng) or Myc-SIRT5 (200 ng)-transfected HEK293T cells with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Myc: 
SIRT5: 
IFN-β: 3456"
  },
  {
    "caption": "ISRE reporter activity (B) in Myc empty vector (200 ng) or Myc-SIRT5 (200 ng)-transfected HEK293T cells with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
SIRT5: 23408"
  },
  {
    "caption": "IFN-β promoter activity (C) in Myc empty vector (200 ng) or Myc-SIRT5 (200 ng)-transfected H1299 cells with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Myc: 
IFN-β: 3456
SIRT5: 23408"
  },
  {
    "caption": "ISRE reporter activity (D) in Myc empty vector (200 ng) or Myc-SIRT5 (200 ng)-transfected H1299 cells with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
SIRT5: 23408"
  },
  {
    "caption": "IFN-β promoter activity (E) in the indicated siRNA-transfected H1299 cells (si-NC, si-SIRT5#1 and si-SIRT5#2) with or without SeV infection (SeV or UI) for 18~24 h. NC, negative control. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "IFN-β: 3456
SIRT5: 23408"
  },
  {
    "caption": "ISRE reporter activity (F) in the indicated siRNA-transfected H1299 cells (si-NC, si-SIRT5#1 and si-SIRT5#2) with or without SeV infection (SeV or UI) for 18~24 h. NC, negative control. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
SIRT5: 23408"
  },
  {
    "caption": "IFN-β promoter activity (G) in SIRT5-deficient H1299 cells (SIRT5 -/-) or the wildtype (WT) H1299 cells (SIRT5 +/+) with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "IFN-β: 3456
SIRT5: 23408"
  },
  {
    "caption": "ISRE reporter activity (H) in SIRT5-deficient H1299 cells (SIRT5 -/-) or the wildtype (WT) H1299 cells (SIRT5 +/+) with or without SeV infection (SeV or UI) for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
SIRT5: 23408"
  },
  {
    "caption": "I ISRE reporter activity in Myc-SIRT5 (0, 100 ng or 200 ng)-transfected HEK293T cells with or without poly(I:C) transfection for 18~24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
SIRT5: 23408"
  },
  {
    "caption": "J ISRE reporter activity in co-transfection of Myc-RIG-I (200 ng) together with Myc-SIRT5 (0, 100 ng or 200ng)-transfected HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
RIG-I: 23586
SIRT5: 23408"
  },
  {
    "caption": "K ISRE reporter activity in co-transfection of Myc-MDA5 (200 ng) together with Myc-SIRT5 (0, 100 ng or 200 ng) in HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
MDA5: 64135
SIRT5: 23408"
  },
  {
    "caption": "L ISRE reporter activity in co-transfection of HA-MAVS (200 ng) together with Myc-SIRT5 (0, 100 ng or 200 ng) in HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "HA: 
ISRE: 
Myc: 
MAVS: 57506
SIRT5: 23408"
  },
  {
    "caption": "M ISRE reporter activity in co-transfection of Myc-TBK1 (200 ng) together with Myc-SIRT5 (0, 100 ng or 200 ng) in HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "ISRE: 
Myc: 
SIRT5: 23408
TBK1: 29110"
  },
  {
    "caption": "N ISRE reporter activity in co-transfection of HA-IRF3 (200 ng) together with Myc-SIRT5 (0, 100 ng or 200 ng) in HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "HA: 
ISRE: 
Myc: 
IRF3: 3661
SIRT5: 23408"
  },
  {
    "caption": "O ISRE reporter activity in co-transfection of HA-MAVS (200 ng) together with Myc-SIRT5 (200ng) or Myc-SIRT5-H158Y(200ng) respectively in HEK293T cells for 24 h. Data information: Graphs represent fold-induction relative to the luciferase activity in the control cells. UI, uninfected. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "HA: 
ISRE: 
Myc: 
MAVS: 57506
SIRT5: 23408"
  },
  {
    "caption": "E Endogenous interaction between MAVS and SIRT5 in the wildtype (WT) (MAVS +/+) or SIRT5-deficient (MAVS -/-) H1299 cells. Anti-MAVS antibody was used for immunoprecipitation, and the interaction was detected by immunoblotting with anti-SIRT5 antibody. Data information: IP, immunoprecipitation; TCL, total cell lysates.",
    "ncbi_link": "MAVS: 57506
SIRT5: 23408"
  },
  {
    "caption": "F GST pull-down assay for GST-tagged MAVS and His-tagged SIRT5. GST-tagged MAVS and His-tagged SIRT5 were expressed in Escherichia coli (BL21), respectively. The association of GST-MAVS with His-SIRT5 was detected by immunoblotting with anti-SIRT5 antibody. GST and GST-MAVS proteins were stained with Coomassie blue.",
    "ncbi_link": "GST: 
His: "
  },
  {
    "caption": "H-I Co-immunoprecipitation analysis of HA-SIRT5 with Flag-MAVS-truncated mutants. HEK293T cells were co-transfected with the indicated plasmids. Anti-Flag antibody conjugated agarose beads were used for immunoprecipitation and the interaction was analyzed by immunoblotting with the indicated antibodies. Flag-MAVS fragments (WT: full length; ΔC1, 1-173 aa; ΔC2, 1-513 aa; ΔN1, 91-540 aa; ΔN2, 173-540 aa; ΔCARD, Δ10-77 aa; ΔPR, Δ103-173 aa; ΔTM, Δ514-535 aa). Data information: IP, immunoprecipitation; TCL, total cell lysates.",
    "ncbi_link": "Flag: 
MAVS: 57506"
  },
  {
    "caption": "H Disruption of SIRT5 in H1299 cells enhanced succinylation of MAVS at Lys 7 compared to that in the SIRT5-intact H1299 cells (SIRT5 +/+) (3.2 vs. 1.0). The cell lysates from SIRT5-deficient H1299 cells or the SIRT5-intact H1299 cells were immunoprecipitated with anti-MAVS antibody or mouse IgG control, followed by immunoblotting with anti-succ-K7-MAVS antibody. Data information: IP, immunoprecipitation; TCL, total cell lysates.",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "I Reconstitution of WT SIRT5 in SIRT5-deficient H1299 cells (SIRT5 -/-) caused a significant reduction in succinylation of MAVS at Lys 7 (1.0 vs. 0.2); but overexpression of SIRT5-H158Y in SIRT5 -/- H1299 cells has no effect on the reduction in succinylation of MAVS at Lys 7 (1.0 vs. 1.2). The SIRT5 -/- H1299 cells were transfected with Flag-SIRT5 or Flag-SIRT5-H158Y, followed by immunoprecipitating with anti-MAVS antibody or mouse IgG control, and immunoblotting with anti-succ-K7-MAVS antibody. Data information: IP, immunoprecipitation; TCL, total cell lysates.",
    "ncbi_link": "Flag: 
SIRT5: 23408"
  },
  {
    "caption": "J-K Knockout of Sirt5 increased Mavs succinylation in mouse livers (J) and lungs (K). Proteins extracted from livers (J) and lungs (K) of Sirt5 KO and the wildtype littermates (n = 3 per group) were detected by the indicated antibodies. MAVS succinylation was determined by anti-succ-K7-MAVS antibody, and anti-pan-succinyl-lysine antibody was used as positive controls.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "A-C Quantitative real time PCR analysis (qPCR) of IFNβ (A), CXCL10 (B) and IFIT1 (C) mRNA in HEK293T cells transfected with the control plasmid (Myc empty) or the plasmid expressing Myc-SIRT5 (Myc-SIRT5) for 24 h, followed by infection with or without SeV (SeV or UI) for 8h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Myc: 
CXCL10: 3627
IFIT1: 3434
IFNβ: 3456
SIRT5: 23408"
  },
  {
    "caption": "D-F qPCR analysis of IFNβ (D), CXCL10 (E), and IFIT1 (F) mRNA in SIRT5-deficient or WT H1299 cells (SIRT5 -/- or SIRT5 +/+) infected with or without SeV (SeV or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "CXCL10: 3627
IFIT1: 3434
IFNβ: 3456
SIRT5: 23408"
  },
  {
    "caption": "G-I qPCR analysis of IFNβ (G), CXCL10 (H) and IFIT1 (I) mRNA in SIRT5-deficient or WT H1299 cells (SIRT5 -/- or SIRT5 +/+) infected with or without VSV (VSV or UI) for 8h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "CXCL10: 3627
IFIT1: 3434
IFNβ: 3456
SIRT5: 23408"
  },
  {
    "caption": "J qPCR analysis of IFNβ mRNA in HEK293T cells transfected with the control plasmid (Myc empty), or the plasmid expressing Myc-SIRT5 (Myc-SIRT5), or its enzyme-deficient mutant H158Y (Myc-SIRT5-H158Y) for 24 h, followed by stimulation with or without poly(I:C) for 8 h. Data information: All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Myc: 
IFNβ: 3456
SIRT5: 23408"
  },
  {
    "caption": "K qPCR analysis of IFNβ mRNA in SIRT5-deficient H1299 cells (SIRT5-/-) transfected with the control plasmid (Myc empty) or the plasmid expressing Myc-SIRT5 (Myc-SIRT5) or its enzyme-deficient mutant H158Y (Myc-SIRT5-H158Y) for 24 h, followed by infection with (+) or without (-) SeV for 8 h. Data information: All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Myc: 
IFNβ: 3456
SIRT5: 23408"
  },
  {
    "caption": "L SDD-AGE analysis of MAVS aggregates in HEK293T cells transfected HA-MAVS together with WT Myc-SIRT5 or its enzyme-deficient mutant (Myc-SIRT5-H158Y) after infected with SeV for 12h. SDS-PAGE immunoblotting was used as a loading control.",
    "ncbi_link": "HA: 
Myc: 
MAVS: 57506
SIRT5: 23408"
  },
  {
    "caption": "M-N IFN-β promoter activity (M) and ISRE reporter activity (N) in HEK293T cells co-transfected Myc-SIRT5 together with HA-MAVS or HA-MAVS-K7R. Data information All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "HA: 
ISRE: 
Myc: 
IFN-β: 3456
MAVS: 57506
SIRT5: 23408"
  },
  {
    "caption": "SIRT5-deficient or WT H1299 cells (SIRT5 -/- or SIRT5 +/+) were infected with VSV-GFP viruses (MOI = 0.1) for 12 h, and viral infectivity was detected by fluorescence microscopy (O)",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "SIRT5-deficient or WT H1299 cells (SIRT5 -/- or SIRT5 +/+) were infected with VSV-GFP viruses (MOI = 0.1) for 12 h and viral infectivity western blot analysis (P) Data information: ll data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "SIRT5-deficient or WT H1299 cells (SIRT5 -/- or SIRT5 +/+) were infected with VSV-GFP viruses (MOI = 0.1) for 12 h, and viral infectivity was detected by flow cytometry analysis (n = 3) (Q).",
    "ncbi_link": "SIRT5: 23408"
  },
  {
    "caption": "A-F qPCR analysis of Ifnβ (A), Ifnα1 (B), Ifnα4 (C), Ifit1 (D), Cxcl10 (E), and Cxcl11 (F) mRNA in WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) infected with or without SeV (SeV or UI) for 8h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Cxcl10: 15945
Cxcl11: 56066
Ifit1: 15957
Ifnα1: 15962
Ifnα4: 15967
Ifnβ: 15977
Sirt5: 68346"
  },
  {
    "caption": "G WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without SeV for the indicated times, and the cell lysates were analyzed by immunoblotting for monomeric (Monomer) and dimeric (Dimer) Irf3 (top; native-PAGE), phosphorylated Irf3 (p-Irf3), total Irf3, Sirt5, and GAPDH (bottom).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "H WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without SeV for 8 h, the interaction between endogenous Mavs and Rig-I was revealed by immunoprecipitation using anti-Mavs antibody, followed by immunoblotting with anti-Rig-I antibody.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "I SDD-AGE analysis of Mavs aggregates in WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) infected with SeV for 12 h. SDS-PAGE immunoblotting was used as a loading control.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "J-O qPCR analysis of Ifnβ (J), Ifnα1 (K), Ifnα4 (L), Ifit1 (M), Cxcl10 (N), and Cxcl11 (O) mRNA in WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) infected with or without VSV (VSV or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Cxcl10: 15945
Cxcl11: 56066
Ifit1: 15957
Ifnα1: 15962
Ifnα4: 15967
Ifnβ: 15977
Sirt5: 68346"
  },
  {
    "caption": "WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without VSV-GFP viruses for 12 h, and viral infectivity was detected by fluorescence microscopy (P)",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without VSV-GFP viruses for 12 h, and viral infectivity was detected by western blot analysis (Q)",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "WT or Sirt5-deficient MEF cells (Sirt5 +/+ or Sirt5 -/-) were infected with or without VSV-GFP viruses for 12 h, and viral infectivity was detected by flow cytometry analysis (n = 3) (R). Data information: All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Ifnβ (A), Ifnα1 (B), Ifnα4 (C), Ifit1 (D), Rig-I (E), Cxcl10 (F) mRNA in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) infected with or without SeV (Sev or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Cxcl10: 15945
Rig-I: 230073
Ifit1: 15957
Ifnα1: 15962
Ifnα4: 15967
Ifnβ: 15977
Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Cxcl11 (G) mRNA in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) infected with or without SeV (Sev or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Cxcl11: 56066
Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Ifnβ (H), Ifnα1 (I) mRNA in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) infected with or without VSV viruses (VSV or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Ifnα1: 15962
Ifnβ: 15977
Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Ifnα4 (J), Ifit1 (K), Rig-I (L) mRNA in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) infected with or without VSV viruses (VSV or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Rig-I: 230073
Ifit1: 15957
Ifnα4: 15967
Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Cxcl10 (M) and Cxcl11 (N) mRNA in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) infected with or without VSV viruses (VSV or UI) for 8 h. Data information: UI, un-infected. The graphs represent fold-induction relative to the untreated cells. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test).",
    "ncbi_link": "Cxcl10: 15945
Cxcl11: 56066
Sirt5: 68346"
  },
  {
    "caption": "O Confocal fluorescence microscopy image of replication in WT or Sirt5-deficient BMDC cells (Sirt5 +/+ or Sirt5 -/-) after infected with VSV-GFP viruses for 12 h (MOI = 1) (fluorescence, upper; bright-field, bottom). Scale bar = 75 µm.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "C-D Knockout of Sirt5 increased Mavs succinylation in mouse livers (C) and lungs (D) upon VSV infection. Proteins in the livers (C) and lungs (D) of Sirt5-deficient or WT littermates (Sirt5 -/- or Sirt5 +/+) injected intraperitoneally with VSV (1 × 107 plaque-forming units (PFU) per mouse)) (n = 3 per group) for 24 h were detected with the indicated antibodies. Mavs succinylation was determined by anti-succ-K7-MAVS antibody. Relative succinylation level was quantified (right panel).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "E Survival (Kaplan-Meier curve) of WT mice (n = 7) and Sirt5-deficient mice (n = 7) injected intraperitoneally with a high dose of VSV (5 × 107 PFU per mouse) and monitored for 10 d.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "F ELISA assay of Ifnβ in serum from the WT mice (n = 4) and Sirt5-deficient mice (n = 4) injected intraperitoneally with VSV (1 × 107 plaque-forming units (PFU) per mouse)) or PBS control for 24 h. Data information: The graphs represent fold-induction relative to the untreated WT mice. PBS, phosphate buffer saline. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test or two-way ANOVA analysis).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Ifnβ (H), Ifnα1 (I), Ifit1 (J), Isg15 (K), Cxcl10 (L), Cxcl11 (M) mRNA in the lungs of WT or Sirt5-deficient mice (Sirt5 +/+ or Sirt5 -/-) injected intraperitoneally with VSV (1 × 107 plaque-forming units (PFU) per mouse) or PBS control for 24 h. Data information: The graphs represent fold-induction relative to the untreated WT mice. PBS, phosphate buffer saline. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test or two-way ANOVA analysis).",
    "ncbi_link": "Cxcl10: 15945
Cxcl11: 56066
Ifit1: 15957
Ifnα1: 15962
Ifnβ: 15977
Isg15: 100038882
Sirt5: 68346"
  },
  {
    "caption": "qPCR analysis of Rig-I (N), and Irf7 (O) mRNA in the lungs of WT or Sirt5-deficient mice (Sirt5 +/+ or Sirt5 -/-) injected intraperitoneally with VSV (1 × 107 plaque-forming units (PFU) per mouse) or PBS control for 24 h. Data information: The graphs represent fold-induction relative to the untreated WT mice. PBS, phosphate buffer saline. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test or two-way ANOVA analysis).",
    "ncbi_link": "Rig-I: 230073
Irf7: 54123
Sirt5: 68346"
  },
  {
    "caption": "P qPCR analysis of VSV mRNA in the lungs of WT or Sirt5-deficient mice (Sirt5 +/+ or Sirt5 -/-) injected intraperitoneally with VSV (1 × 107 plaque-forming units (PFU) per mouse) or PBS control for 24 h. Data information: The graphs represent fold-induction relative to the untreated WT mice. PBS, phosphate buffer saline. All data are presented as the mean values based on three independent experiments, and error bars indicate S.E.M. (unpaired two-tailed Student's t test or two-way ANOVA analysis).",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "Representative immunofluorescence (IF) staining of Ki67 and TDP-43 in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI; upper panel in blue) or neural marker NeuN (lower panel in green). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Representative data of reverse-transcription PCR (left panel) or Western blot (right panel) for cell cycle-related genes and semi-quantification of the expression levels in the frontal cortices and hippocampus from the 6-mon-old WT and FTLD-TDP Tg mice. N = 5 mice per group, data are presented as mean ± SEM (%), statistical analysis by multiple t-test with FDR correction, Q = 1%. *P < 0.05, **P ≤ 0.01; ***P ≤ 0.001 and ****P ≤ 0.0001",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Representative image of comet assay for DNA fragmentation and the quantification of cells with comet tails in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Scale bar: 50 μm. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, *p = 0.0114 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Representative IF staining of γH2AX and TDP-43 in the regions of frontal cortices from 6-mon-old WT and FTLD-TDP Tg mice. Nuclei were stained with DAPI (upper panel in blue) or NeuN (middle panel in green). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm. Lower panel: quantification of cells or neurons with γH2AX immunoreactivity and TDP-43 proteinopathies from each view of microscope. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, ***p = 0.0008 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Representative IF staining of γH2AX and Ki67 in the regions of frontal cortices from WT and FTLD-TDP Tg mice. Nuclei were stained with DAPI (upper panel) or NeuN (middle panel). Scale bar: 50 μm. Subregions, scale bar: 15 μm. Lower panel: quantification of cells or neurons with γH2AX and Ki67 immunoreactivity from each view of microscope. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM, ***p = 0.0004 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Top, representative western blot data of HDAC1 and TDP-43 in extracts obtained following RIPA fractional extraction in the frontal cortices and hippocampus from 6-mon-old of FTLD-TDP or WT mice. Bottom, semi-quantification of HDAC1 and TDP-43 expression levels. N = 5 mice per group, data are presented as mean ± SEM (%), **** p < 0.0001 by multiple t-tests.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "IF staining of HDAC1 and SMI-32 in the regions of frontal cortices from WT and FTLD-TDP Tg mice. Scale bar: 150 μm. Blocked area in left bottom picture is showed in a magnified view in the right bottom picture. Scale bar: 50 μm.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Nuclear HDAC1 activity assay from frontal cortices and hippocampus in 6-mon-old of FTLD-TDP and WT mice. TSA: nuclear extracts that were treated with Trichostatin A (TSA, an HDAC inhibitor) as a negative control for HDAC1-transferred fluorescent activity during the HDAC1 activity assay. N = 5 mice per group, data are presented as mean ± SEM (%), *p = 0.0415 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Left, representative western blot data of nuclear acetylated-histone H3 (Lys 9/14) and total-histone H3 in 6-mon-old of WT and FTLD-TDP Tg mice. Right, quantification of nuclear acetylated-histone H3/total-histone H3 ratio. N = 5 mice per group, data are presented as mean ± SEM (%), * p = 0.0147 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Left graph: IF staining of TDP-43 and HDAC1 during progression of TDP-43 proteinopathies in the frontal cortices from the FTLD-TDP Tg and WT mice. Nuclei were stained with DAPI (in blue). Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm. Right histogram: Quantification of co-localized TDP-43 and HDAC1 immunoreactivity in the cytosol or nucleus in the WT or 1-, 6-, and 12-month-old FTLD-TDP Tg mice. n = 9 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM. *Nucleus: Tg 1m vs. Tg 6m or 12m; #Cytosol: Tg 1m vs. Tg 6m or 12m; @ Tg 6m vs Tg 12m. ****/####/@@@@ p < 0.0001 by multiple comparison.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Left graph: IF staining of γH2AX and HDAC1 in the frontal cortices from the 12-month-old FTLD-TDP Tg and WT mice. Nuclei were stained with DAPI (in blue). Arrow head: γH2AX+ nucleus; arrow: mislocalized HDAC1. Scale bar: 50 μm. Right histogram: Quantification of γH2AX+ and HDAC1 mislocalized cells in the WT or 1-, 6-, and 12-month-old FTLD-TDP Tg mice. n = 4 sections per mouse, N = 5 mice per group, data are presented as mean ± SEM. ** p = 0.0079, **** p < 0.0001 by multiple comparison.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Left panel: flag-tagged full-length HDAC1 was overexpressed with myc-tagged TDP-43 in HEK-293T cells; the cell lysates were immunoprecipitated for flag and immunoblotted for TDP-43 and flag. Right panel: myc-tagged TDP-43 was overexpressed with flag-tagged full-length HDAC1 in HEK-293T cells; the cell lysates were immunoprecipitated for myc and immunoblotted for flag and TDP-43.",
    "ncbi_link": "flag: 
myc: 
HDAC1: 433759
TDP-43: 230908"
  },
  {
    "caption": "Upper left: flag-tagged full-length HDAC1 (b.Ⅰ) or various truncation mutations (b.Ⅱ-Ⅳ) were overexpressed with myc-tagged TDP-43; the catalytic domain is indicated in red. Lower panel: the western blotting of cell lysates immunoprecipitated for flag and immunoblotted for TDP-43.",
    "ncbi_link": "flag: 
myc: 
HDAC1: 433759
TDP-43: 230908"
  },
  {
    "caption": "Upper panel: Immunoprecipitation of cytosolic HDAC1 and immunoblotting of HDAC1 and TDP-43 in WT and FTLD-TDP Tg mice. Lower histogram: Quantification of immunoprecipitation results of HDAC1 and TDP-43 in WT and Tg mice. N = 5 mice per group, data are presented as mean ± SEM (%), * p =0.0149, *** p =0.0003 by t-test.",
    "ncbi_link": "TDP: 230908"
  },
  {
    "caption": "Representative IF staining of TDP-43 and HDAC1 in the frontal cortices from normal individuals and patients with FTLD-TDP. Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "ncbi_link": "TDP: 23435"
  },
  {
    "caption": "Representative IF staining of γH2AX and Ki67 in the frontal cortices from normal individuals and patients with FTLD-TDP from each view of microscope. Scale bar: 50 μm. The circled area is emphasized for showing the distribution of immunoreactivity in cell subregions. Scale bar: 15 μm.",
    "ncbi_link": "TDP: 23435"
  },
  {
    "caption": "Dot-blot of HDAC1 and TDP-43 in urea-soluble fractions from the frontal cortex of normal individuals and patients with FTLD-TDP.",
    "ncbi_link": "TDP: 23435"
  },
  {
    "caption": "B. Characterization of the various B cell progenitor fractions as described by [38] in the bone marrow of 4 wildtype and 4 Shld2−/− littermate controls.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "C. Characterization of the indicated thymic T cell populations in the bone marrow of 4 wildtype and 4 Shld2−/− littermate controls.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "D. Characterization of the indicated immature and mature splenic B cell populations in the bone marrow of 4 wildtype and 4 Shld2−/− littermate controls.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "E. Characterization of the indicated peritoneal B cell populations in the bone marrow of 4 wildtype and 4 Shld2−/− littermate controls.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "F. Left panel: Schematic of the A70.2 INV-4 cell line strategy to induce RAG1/2-mediated recombination using imatinib. Right panel: A70.2 INV-4 cell lines were transduced with lentiviruses encoding the lentiCRISPRv2 expressing sgRNAs against the 53bp1, Shld1, Shld2, Shld3, and Lig4 genes. Guide RNA targeting chicken AID was used as a negative control (Ctrl). Cells were selected with puromycin and treated with 3 μM imatinib for 4 days after which GFP frequency was measured (mean ± SD of 3 biological replicates). The insertion-deletion (indel) penetrance as measured by TIDE analysis [39] of sequence for each of these sgRNA constructs is shown in Figure EV1E, and the baseline GFP frequency prior to imatinib stimulation is shown in Figure EV1F. sgRNA sequences used are shown in Table EV2.",
    "ncbi_link": "AID: 
GFP: 
Lig4: 319583
Shld1: 73747
Shld2: 75698
Shld3: 113002583
53bp1: 27223"
  },
  {
    "caption": "A. Concentration of the various indicated isotypes in the serum of 6-8 week old unimmunized WT and Shld2−/− mice. Values are mean concentration ± SD of 4 biological replicates; ** P ≤ 0.01, unpaired two-tailed t-test.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "B. B cells were purified from spleens from WT and Shld2−/− mice, and stimulated to undergo CSR to the various indicated isotypes using different stimulation cocktails [33]. Cells were then analyzed by flow cytometry for expression of the various indicated isotypes and the percent expression of each isotype are reported. Values are mean frequency ± SD of 4 biological replicates; **** P ≤ 0.0001, unpaired two-tailed t-test.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "C. WT, 53bp1−/−, and Shld2−/− mice were immunized with NP-CGG and the serum was withdrawn 2 weeks post immunization and serial dilutions were subjected to ELISA analysis for NP-specific antibodies of the indicated isotypes. Values are mean absorbance ± SD of 4 biological replicates.",
    "ncbi_link": "Shld2: 75698
53bp1: 27223"
  },
  {
    "caption": "D. WT, 53bp1−/−, and Shld2−/− mice were immunized with NP-CGG, spleens were isolated and anti-IgG secreting cells were enumerated by the ELISPOT assay. Values are mean frequency ± SD of 4 biological replicates, except for Shld2-/- (n=3); * P ≤ 0.05, ** P ≤ 0.01, unpaired two-tailed t test.",
    "ncbi_link": "Shld2: 75698
53bp1: 27223"
  },
  {
    "caption": "A. WT and Shld2−/− B cells were purified from spleens and stimulated with LPS + IL4 and examined for IgM and IgG1 expression 3, 6, and 9 days post-stimulation by flow cytometry. Representative plots are shown for both WT and Shld2−/− B cells 6-days post stimulation. The graph plots show proportion of IgG1+ and Iglo cells, mean ± SD from 6 biological replicates; ** P ≤ 0.01, *** P ≤ 0.001, two-way ANOVA with post hoc Dunnett's test.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "B. WT CH12 cells, as well as two each of 53BP1-, SHLD1-, SHLD2-, and SHLD3-deficient clones generated previously [21], as well as a LIG4-deficient CH12 clone were subjected to CSR induction with the CIT cocktail and measured for both IgM and IgA expression by flow cytometry. Representative flow plots for WT and 53bp1−/− CH12 cells are shown at day 3 post CIT stimulation. The graph plots show proportion of IgA+ and Iglo CH12 cells, mean ± SD from 3 biological replicates; * P ≤ 0.05, **** P ≤ 0.0001, two-way ANOVA with post hoc Dunnett's test. The letters below the x-axis represent the clone codes for the 53BP1, SHLD1, SHLD2, and SHLD3-deficient CH12 clones. One LIG4-deficient CH12 clone was also used.",
    "ncbi_link": "LIG4: 319583
SHLD1: 73747
SHLD2: 75698
SHLD3: 113002583
53bp1: 27223
53BP1: 27223"
  },
  {
    "caption": "C. The Xlf, Ku70, Ku80, Xrcc4, and Paxx genes were knocked out in CH12 cells by CRISPR, and two independent clones each were analyzed as in Figure 3B with mean ± 3 biological replicates; * P ≤ 0.05, **** P ≤ 0.0001, two-way ANOVA with post hoc Dunnett's test.",
    "ncbi_link": "Paxx: 227622
Xlf: 227622
Xrcc4: 108138
Ku80: 22596
Ku70: 14375"
  },
  {
    "caption": "A. WT, and two independent clones each of 53bp1−/−, Shld2−/−/−, and Shld3−/− CH12 cells were stimulated with CIT and analyzed by flow cytometry for IgM and IgA expression. The Iglo population were reduced after 7 days in culture. Values are mean ± SD from 3 biological replicates; * P ≤ 0.05, ** P ≤ 0.01, **** P ≤ 0.0001, two-way ANOVA with post hoc Dunnett's test.",
    "ncbi_link": "Shld2: 75698
Shld3: 113002583
53bp1: 27223"
  },
  {
    "caption": "B. WT, and two independent clones each of 53bp1−/−, Shld2−/−/−, and Shld3−/− CH12 clones were stimulated with CIT for 3 days. The IgM+, IgA+, and Iglo populations were sorted and reanalyzed for expression of IgM and IgA 5 days post sort as well as 12 days post sort (see Figure EV4B). Shown on bar graphs are sorted IgM+, IgA+, and Iglo populations (each column, 1 technical replicate) from WT and mutant CH12 clones, and the percent of cells expressing IgM, IgA, or low for both isotypes (Iglo) after 5 days of culture post-sort. A representative flow plot of 53bp1−/− CH12 3 days post CIT treatment is shown.",
    "ncbi_link": "Shld2: 75698
Shld3: 113002583
53bp1: 27223"
  },
  {
    "caption": "A. mRNA expression analysis of IgM and IgA was carried out by RT-PCR for Iglo subclones from WT and two independent 53bp1−/− CH12 (TA and T1) clones. The Iglo subclones derived from the 53bp1−/− CH12 TA clone are listed as D01-D18, while the Iglo subclones derived from the 53bp1−/− CH12 T1 clone are listed as F03-F24. Gels show the RT-PCR analysis for IgM cDNA (top), IgA cDNA (middle), and AID cDNA (bottom) as control.",
    "ncbi_link": "AID: 
IgA: 238447
IgM: 16019
53bp1: 27223"
  },
  {
    "caption": "B. mRNA expression analysis as in A of Iglo subclones of two independent Shld2-/-/- (F2 and F3) clones, and IgA+ subclones from Shld2-/-/- clone F3. The Iglo subclones derived from the Shld2-/-/- CH12 F2 clone are listed as H03-H40, while the Iglo subclones derived from the Shld2-/-/-CH12 F3 clone are listed as J02-J109.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": "Long-range PCR of Iglo subclones from WT and two independent 53bp1-/- CH12 (TA and T1) clones. The Iglo subclones derived from the 53bp1−/− CH12 TA clone are listed as D01-D18, while the Iglo subclones derived from the 53bp1−/− CH12 T1 clone are listed as F03-F24. Gels show long-range amplicons (top) and AID genomic DNA PCR control (bottom).",
    "ncbi_link": "AID: 
53bp1: 27223"
  },
  {
    "caption": "Long-range PCR as in B of Iglo subclones of two independent Shld2-/-/- (F2 and F3) clones (left 2 panels), and IgA+ subclones from Shld2-/-/- clone F3.",
    "ncbi_link": "Shld2: 75698"
  },
  {
    "caption": " C. HEK293 cells were treated for 8 h with 100 μM H2O2 in the presence or absence of the Nrf2 inhibitor trigonelline (Trig). Heme oxygenase 1 (HMOX-1), glutamate:cysteine ligase (GCL) and GSNOR expressions were evaluated RT-qPCR analyses Results shown are the means ± SEM of n = 3 experiments run in triplicate. *p<0.05; n.s., not significant. ",
    "ncbi_link": "GSNOR: 128
GCL: 2729
glutamate:cysteine ligase: 2729
Heme oxygenase 1: 3162
HMOX-1: 3162"
  },
  {
    "caption": " D. RT-qPCR analyses of GSNOR mRNA after 2-to-24 h incubation with 100 μM H2O2. Results shown are the means ± SEM of n = 3 experiments run in triplicate, analyzed using ANOVA with Dunnett multiple comparisons test. n.s., not significant. ",
    "ncbi_link": "GSNOR: 128"
  },
  {
    "caption": " I. RT-qPCR analyses of GSNOR mRNA in input and heavy polysome fraction pooled together in H2O2-treated samples (for either 8 or 24 h). H3A mRNA expression level was used as housekeeping gene control. Results represent the means ± SD of n ≥ 6 independent experiments shown as % normalized by H3A. ***, p<0.001 Vehicle: PBS. ",
    "ncbi_link": "GSNOR: 128
H3A: 8350"
  },
  {
    "caption": " D. HEK293 cells were transfected with a pool of siRNA against ATM (siATM) or with control siRNA (siScr) for 18 h and treated for additional 24 h with 100 μM H2O2. Basal and phospho-active forms of ATM, together with GSNOR were assessed by Western blot. Vinculin and GAPDH were used as loading controls. Densitometry of GSNOR immunoreactive bands is normalized to GAPDH and expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05; **, p<0.01. ",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": " E. HEK293 cells were transfected with a pool of siRNA against CHK2 (siCHK2) or with control siRNA (siScr) for 18 h and treated for additional 24 h with 100 μM H2O2. Basal and phospho-active forms of CHK2, together with GSNOR were assessed by Western blot. GAPDH was used as loading control. Densitometry of GSNOR immunoreactive bands is normalized to GAPDH and expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05. ",
    "ncbi_link": "CHK2: 11200"
  },
  {
    "caption": " G. RT-qPCR analyses of GSNOR mRNA in input and heavy polysome fraction pooled together in H2O2 treated samples in the absence or in the presence of the ATM inhibitor KU55933 (KU). H3A mRNA expression level was used as housekeeping gene control. Results are the means ± SEM of n = 3 independent experiments run in duplicate and shown as %, normalized by H3A. *, p<0.05. ",
    "ncbi_link": "GSNOR: 128
H3A: 8350"
  },
  {
    "caption": " I. HEK293 cells were transfected with a pool of siRNA against CHK1 (siCHK1) or with control siRNA (siScr) for 18 h and treated for additional 24 h with 100 μM H2O2. CHK1 and GSNOR were assessed by Western blot analysis of. Densitometry of GSNOR immunoreactive bands is normalized to Vinculin, selected as loading control, and expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05. ",
    "ncbi_link": "CHK1: 1111"
  },
  {
    "caption": " F. HEK293 cells were transfected with plasmids coding for the wild-type (WT), C2991L redox mutant (CL) of ATM, or with an empty vector (Empty) (used as negative control) for 40 h and treated for additional 8 h with 100 μM H2O2. Basal and phospho-active forms of ATM, and GSNOR were assessed by Western blot analysis. Vinculin and GAPDH were used as loading controls. Two different exposures (low and high) were selected to highlight differences in P-ATM levels in different experimental settings. ",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": " B. HEK293 cells were transfected with a pool of siRNA against p53 (sip53) or with control siRNA (siScr) for 24 h and treated for additional 24 h with 100 μM H2O2. Basal and phospho-active forms of ATM and CHK2, as well as p53 and GSNOR were assessed by Western blot. Phospho:basal level ratios of ATM and CHK2 (normalized to Vinculin), along with densitometry of GSNOR immunoreactive bands (normalized to GAPDH) are expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05; **, p<0.01; n.s., not significant. ",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": " C. HCT116 cells expressing the wild type form of p53 (p53wt), or an empty vector (Empty, selected as negative control), were treated for 24 h with 100 μM H2O2. Basal and phospho-active forms of ATM and CHK2, p53 and GSNOR were assessed by Western blot. Vinculin and GAPDH were used as loading controls. Phospho:basal level ratios of ATM and CHK2, along with densitometry of p53 and GSNOR immunoreactive bands are expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05; **, p<0.01; n.s., not significant. ",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": " C. HEK293 were transfected for 48 h with siRNA against ATM (siATM), GSNOR (siGSNOR), or control siRNA (scramble, siScr). Afterwards, they were treated for 8 h with 100 μM H2O2 and mitophagy was assessed by Western blot of different mitochondrial complex subunits [i.e., NDUFB8 (complex I), SDHB (complex II), MTCO2 (complex IV)]. Basal and phospho ATM, as well as GSNOR were used to check the efficiency of siRNA-mediated knock down. Vinculin was used as loading control. ",
    "ncbi_link": "GSNOR: 128
ATM: 472"
  },
  {
    "caption": " E. In the same experimental settings, mitophagy was also assessed by RT-qPCR relative quantitation of D-loop (selected as measure of mtDNA) normalized to genomic actin (gActin). Results shown are the means ± SD of n = 8 experiments ***p<0.001; n.s., not significant. ",
    "ncbi_link": "gActin: 
genomic actin: "
  },
  {
    "caption": " F. U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 4 h with 100 μM H2O2. Mitophagy was assessed by RT-qPCR relative quantitation of D-loop normalized to genomic actin (gActin). Results shown are the means ± SD of n = 6 experiments. *p<0.05; ***p<0.001. ",
    "ncbi_link": "gActin: 
genomic actin: 
GSNOR: 128
ATM: 472"
  },
  {
    "caption": " A, B. ATMWT U2OS cells were treated with 10 μM CCCP for 8 h. After treatment, cells were incubated with 5 μM 2',7'-H2DCF-DA (A) or MitoSox (B) to evaluate the production of H2O2 or mitochondrial superoxide, respectively. Values are shown as units of DCF or MitoSox fluorescence relative to untreated cells (arbitrarily set as 1) and represent the means ± SD of n = 3 independent experiments. ***p< 0.001. ",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": " U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 2 h with 10 μM CCCP. Mitophagy was evaluated by: (D) RT-qPCR relative quantitation of D-loop normalized to genomic actin (gActin). Results shown are the means ± SD of n = 4 experiments. *p<0.05; **p<0.01; ***p<0.001. ",
    "ncbi_link": "gActin: 
genomic actin: 
GSNOR: 128
ATM: 472"
  },
  {
    "caption": " U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 2 h with 10 μM CCCP. (E fluorescence microscopy analyses upon incubation with chloroquine (CLQ) to enhance differences in mitophagy. Anti-TOM20 (red) was used to visualize mitochondria; anti-LC3 (green) was used to identify autophagosomes. ",
    "ncbi_link": "GSNOR: 128
ATM: 472"
  },
  {
    "caption": " U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 2 h with 10 μM CCCP. F) fluorescence microscopy analyses upon incubation with chloroquine (CLQ) to enhance differences in mitophagy. Percentage of mitochondria merging with LC3-positive puncta calculated by Fiji analysis software using the open-source plugin ComDet v. 0.3.7. Values are expressed as % of mitochondria (TOM20+ particles) co-localizing with LC3/cell and graphed as boxes (25th-75th interquartile range) and whiskers (minimum to maximum showing all points), with central bands representing the median of n ≥ 9 different cells. **p<0.01; ***p<0.001; n.s., not significant. ",
    "ncbi_link": "GSNOR: 128
ATM: 472"
  },
  {
    "caption": " U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 2 h with 10 μM CCCP. (G Western blot of different subunits of mitochondrial proteins, i.e., NDUFB8 (complex I), SDHA and SDHB (complex II), MTCO2 (complex IV) and voltage-dependent anion channel (VDAC). Tubulin, LDH and Vinculin were used as loading controls. ",
    "ncbi_link": "GSNOR: 128
ATM: 472"
  },
  {
    "caption": " U2OS cells were depleted of endogenous ATM by repeated transfections with shRNA and induced, by doxycycline incubation, to express ATMWT, ATM2RA, or ATMCL mutant. Where indicated, cells were further transfected with a GSNOR-coding vector and then treated for 2 h with 10 μM CCCP. H) Densitometry of mitochondrial protein immunoreactive bands and expressed as arbitrary units. Values shown represent the means ± SD of n = 3 independent experiments. *, p<0.05; **, p<0.01; ***, p<0.001; n.s., not significant. ",
    "ncbi_link": "GSNOR: 128
ATM: 472"
  },
  {
    "caption": " B. HEK293 cells overexpressing the wild type form of GSNOR (GSNORwt) or an empty vector (Empty) were subjected to combined treatment (200 μM H2O2 + 400 μM DPTA) in the presence or absence of the ATM inhibitor KU55933 (KU). Analysis of dead cells were performed with Trypan blue exclusion assay. Western blot analysis of GSNOR is shown as inset in the graph to substantiate transfection efficiency. Data, shown as fold change of dead cells relative to untreated cells (arbitrarily set to 1), represent the mean count ± SEM of n = 4 experiments done in duplicate *p<0.05; with respect to Empty cells. ",
    "ncbi_link": "GSNOR: 128"
  },
  {
    "caption": " C. Representative optic microscopy image of GSNORwt and Empty cells upon 24 h treatment with H2O2 + DPTA in the presence KU. ",
    "ncbi_link": "GSNOR: 128"
  },
  {
    "caption": "D. Western blot analysis of Caspase3 and PARP1 in GSNORwt and Empty cells treated as in panel C. Tubulin was used as loading control.",
    "ncbi_link": "GSNOR: 128"
  },
  {
    "caption": " E. HEK293 cells overexpressing the wild type form of GSNOR (GSNORwt) or an empty vector (Empty) were transfected with siRNA against Pakin (siParkin) or control siRNA (scramble, siScr). Afterwards, they were subjected to combined treatment (200 μM H2O2 + 400 μM DPTA) and viability assessed by Alamar blue (AB) fluorescent assay. Data, shown as fold change of viable cells, refer to AB fluorescence (relative to untreated cells, arbitrarily set to 1) and represent the means ± SD of n = 6 independent experiments. **, p<0.01; n.s., not significant. ",
    "ncbi_link": "GSNOR: 128
Pakin: 5071
Parkin: 5071"
  },
  {
    "caption": " F. Western blot of Gsnor was assessed in mouse adult fibroblasts (MAFs), obtained from wild type (WT) and Gsnor-null (KO) mice treated with 200 or 400 μM H2O2 for 24 h. ",
    "ncbi_link": "Gsnor: 11532"
  },
  {
    "caption": " WT and Gsnor KO MAFs were subjected to treatment with 200 μM H2O2, or 400 μM DPTA, or a combination of both. Cell viability was evaluated by LIVE/DEAD assay. ",
    "ncbi_link": "Gsnor: 11532"
  },
  {
    "caption": " H. WT and Gsnor KO MAFs were subjected to treatment with 200 μM H2O2, or 400 μM DPTA, or a combination of both. Cell viability was evaluated by LIVE/DEAD assay. Scale bar = 50 µm. Data, shown as % of dead (red) cells, represent the mean count ± SD of n = 3 different fields of three independent experiments. *p<0.05; n.s., not significant with respect to WT MAFs. ",
    "ncbi_link": "Gsnor: 11532"
  },
  {
    "caption": "A, B. HeLa cells treated with non-targeting siRNA (Ctrl) or C9orf72 siRNA and transfected with mCherry-EGFP-LC3 were treated with vehicle (Ctrl), Torin1 (250 nM; 3 h), bafilomycin A1 (100 nM; 6 h - BafA1) or combinations thereof as indicated. Autophagosomes (green+red) and autolysosomes (red only) were quantified per cell (Mean ± SEM from 3 independent experiments; one-way ANOVA with Fisher's LSD test: ns, not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001; N (cells) = Ctrl/Ctrl: 120; Ctrl/Torin1: 101; C9orf72/Ctrl: 99; C9orf72/Torin1: 106; Ctrl/BafA1: 116; Ctrl/Torin1/BafA1: 118; C9orf72/BafA1: 109; C9orf72/Torin1/BafA1: 106). Scale bar = 20 µm. C9orf72 knockdown was confirmed by RT-qPCR (Appendix Fig S2).",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "C, D. HEK293 cells treated with non-targeting (Ctrl) or C9orf72 siRNA were incubated with BafA1, BafA1+Torin1 (C) or BafA1+rapamycin (D) and levels of LC3-I and II were determined on immunoblots. Levels of LC3-II were normalized against α-tubulin and are shown relative to the BafA1-treated sample (Mean ± SEM; one-way ANOVA with Fisher's LSD test: ns, not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001; N = 3 experiments).",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "E, F. Primary cortical neurons (DIV5/6) were transfected with ECFP non-targeting (Ctrl) or C9orf72 miRNA (cyan) and EGFP-LC3 (green). 3 days post transfection neurons were treated with vehicle (Ctrl), Torin1 (250 nM; 3 h), BafA1 (100 nM; 5 h) or combinations thereof as indicated. Autophagosomes were quantified as the number of EGFP-LC3 positive puncta per soma from 2 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test: ns, not significant, * p ≤ 0.05; *** P ≤ 0.001; **** P ≤ 0.0001; N (cells) = Ctrl miRNA/Ctrl: 77; Ctrl miRNA/Torin1: 68; C9orf72 miRNA/Ctrl: 57; C9orf72 miRNA/Torin1: 69; Ctrl miRNA/BafA1: 35; Ctrl miRNA/Torin1/BafA1: 57; C9orf72 miRNA/BafA1: 66; C9orf72 miRNA/Torin1/BafA1: 64). Scale bar = 5 µm.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "A. HEK293 cells treated with non-targeting (Ctrl) or FIP200 siRNA were co-transfected with EGFP-LC3 and either empty vector control (EV), Myc-C9orf72S or Myc-C9orf72L. 24 h post transfection cells were treated with vehicle or 100 nM BafA1 for 6 h. Samples were lysed and subjected to SDS-PAGE and immunoblot. Autophagy levels were determined by immunoblot for EGFP-LC3-I and II. Expression of Myc-C9orf72 was confirmed using anti-Myc (* indicates a nonspecific band). FIP200 knockdown was confirmed using anti-FIP200 antibodies. α-tubulin was used as loading control.",
    "ncbi_link": "C9orf72: 203228
FIP200: 9821"
  },
  {
    "caption": "B. HeLa cells treated with non-targeting (Ctrl) or FIP200 siRNA were co-transfected with empty vector (EV), Myc-C9orf72S or Myc-C9orf72L (red) and EGFP-LC3 (green) to label autophagosomes. As positive control EV transfected cells were treated for 3 h with Torin1 (250 nM). Autophagy was quantified as the number of EGFP-LC3 positive autophagosomes per cell from 3 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test: **** P ≤ 0.0001, N (cells) = Ctrl/EV: 73; FIP200/EV: 76; Ctrl/EV/Torin1: 73, FIP200/EV/Torin1: 70; Ctrl/C9orf72L: 71; FIP200/C9orf72L: 74; Ctrl/C9orf72S: 72; FIP200/C9orf72S: 72). Scale bar = 20 µm. FIP200 knockdown was confirmed by immunoblot (Appendix Fig S2).",
    "ncbi_link": "C9orf72: 203228
FIP200: 9821"
  },
  {
    "caption": "A, B, C. Cell lysates of HEK293 cells co-transfected with FLAG-FIP200 (A) and either empty vector control, Myc-C9orf72S or Myc-C9orf72L were subjected to immunoprecipitation with anti-Myc (A and B) antibodies. Immune pellets were probed for Myc-C9orf72 (A and B), FLAG-FIP200 (A) on immunoblots.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "A, B, C. Cell lysates of HEK293 cells co-transfected with HA-ULK1 (B) and either empty vector control, Myc-C9orf72S or Myc-C9orf72L were subjected to immunoprecipitation with anti-Myc (A and B) antibodies. Immune pellets were probed for Myc-C9orf72 (A and B), HA-ULK1 (B) on immunoblots.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "A, B, C. Cell lysates of HEK293 cells co-transfected with Myc-ATG13 (C) and either empty vector control, FLAG-C9orf72S or FLAG-C9orf72L were subjected to immunoprecipitation with anti-FLAG (C) antibodies. Immune pellets were probed for FLAG-C9orf72 (C), Myc-ATG13 (C) on immunoblots.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "D, E. Cell lysates of HEK293 cells transfected with empty vector control, Myc-C9orf72S or Myc-C9orf72L were subjected to immunoprecipitation with anti-Myc antibodies Immune pellets were probed for Myc-C9orf72 and endogenous FIP200, ULK1, and ATG13. There are multiple alternatively spliced forms of ATG13 (Jung et al., 2009; Alers et al., 2011); ATG13* is most likely a smaller alternative spliced form of ATG13 that is enriched by interaction with C9orf72.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "F, G, H. HeLa cells transfected with Flag-FIP200 and Myc-C9orf72 were fixed and processed for PLA analysis. Transfections were laced with mVenus to enable identification of transfected cells for analysis where required (green). PLA signals (red) were counted per cell (Mean ± SEM; one-way ANOVA with Fisher's LSD test, **** P ≤ 0.0001; N (cells) = (F) C9orf72S: 22; C9orf72L: 18; EV+FIP200: 18; C9orf72S+FIP200: 18; C9orf72L+FIP200: 17. Scale bar = 10 µm; see also Fig EV2.",
    "ncbi_link": "FIP200: 9821"
  },
  {
    "caption": "F, G, H. HeLa cells transfected with HA-ULK1 and Myc-C9orf72 were fixed and processed for PLA analysis. Transfections were laced with mVenus to enable identification of transfected cells for analysis where required (green). PLA signals (red) were counted per cell (Mean ± SEM; one-way ANOVA with Fisher's LSD test, **** P ≤ 0.0001; N (cells) = (G) C9orf72S: 21; C9orf72L: 20; EV+ULK1: 20; C9orf72S+ULK1: 22; C9orf72L+ULK1: 20. Scale bar = 10 µm; see also Fig EV2.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "F, G, H. HeLa cells transfected with Myc-ATG13 and EGFP-C9orf72 were fixed and processed for PLA analysis. Transfections were laced with mVenus to enable identification of transfected cells for analysis where required (green). PLA signals (red) were counted per cell (Mean ± SEM; one-way ANOVA with Fisher's LSD test, **** P ≤ 0.0001; N (cells) = (H) C9orf72S: 11; C9orf72L: 10; EV+ ATG13: 11; C9orf72S+ATG13: 11; C9orf72L+ATG13: 11). Scale bar = 10 µm; see also Fig EV2.",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "A. HEK293 cells were transfected with non-targeting (Ctrl) or C9orf72 siRNA. Cells were treated with rapamycin for 6 h to induce autophagy. Activation of ULK1 was determined on immunoblots using phospho-ULK1 (Ser757), total ULK1 and GAPDH Abs (loading control).",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "B. HeLa cells treated with non-targeting (Ctrl) or C9orf72 siRNA were transfected with mCherry-FIP200. 24 h post transfection cells were treated for 3 h with Torin1 (250 nM) or vehicle (Ctrl). Translocation of the ULK1 complex was quantified as the number of mCherry-FIP200 positive puncta per cell from 3 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, ns: not significant, **** P ≤ 0.0001; N (cells) = Ctrl/Ctrl: 65; Ctrl/Torin1: 60; C9orf72/Ctrl: 54; C9orf72/Torin1: 49). C9orf72 knockdown was determined by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "C. Primary cortical neurons (DIV5/6) were transfected with EmGFP non-targeting (Ctrl) or C9orf72 miRNA (green) and mCherry-FIP200 (red); for rescue experiments the cells were additionally transfected with mCerulean-tagged C9orf72s and C9orf72L (cyan). 3 days post transfection neurons were treated for 3 h with Torin1 (250 nM) or vehicle (Ctrl). Translocation of the ULK1 complex was quantified as the number of mCherry-FIP200 positive puncta per soma from 2 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, ns: not significant, *** P ≤ 0.001, **** P ≤ 0.0001; N (cells) = Ctrl miRNA/Ctrl: 134; Ctrl miRNA/Torin1: 125; C9orf72 miRNA/Ctrl: 101; C9orf72 miRNA/Torin1: 78; C9orf72 miRNA+C9orf72L+C9orf72S: 41; C9orf72 miRNA+C9orf72L+C9orf72S/Torin1: 39). Scale bar = 5 µm.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "D. HeLa cells were co-transfected with mCherry-FIP200 (red) and empty vector (EV), FLAG-C9orf72L or FLAG-C9orf72S (green). As positive control EV transfected cells were treated for 3 h with Torin1 (250 nM). Translocation of the ULK1 complex was quantified as the number of mCherry-FIP200 positive puncta per cell from 3 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, *** P ≤ 0.001, **** P ≤ 0.0001); N (cells) = EV: 47, EV + Torin1: 31, C9orf72L: 46, C9orf72S: 45). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "A, B. HeLa cells (A) or SH-SY5Y neuroblastoma cells (B) treated with non-targeting (Ctrl) or Rab1a siRNA were co-transfected with mCherry-FIP200 (red) and empty vector (EV), Myc-C9orf72L or Myc-C9orf72S (green). As positive control EV transfected cells were treated for 3 h with Torin1 (250 nM). Translocation of the ULK1 complex was quantified as the number of mCherry-FIP200 positive puncta per cell (A, HeLa, Mean ± SEM; one-way ANOVA with Fisher's LSD test; ns, not significant; **** P ≤ 0.0001; N (cells from 3 independent experiments) = Ctrl/EV: 81; Ctrl/EV/Torin1: 48; Ctrl/C9orf72L: 86; Ctrl/C9orf72S: 48; Rab1a/EV: 79; Rab1a/EV/Torin1: 68; Rab1a/C9orf72L: 78; Rab1a/C9orf72S: 52; B, SH-SY5Y: Mean ± SEM; one-way ANOVA with Fisher's LSD test; ns, not significant; ** P ≤ 0.01; **** P ≤ 0.0001; N (cells from 2 independent experiments) = Ctrl/EV: 70; Ctrl/EV/Torin1: 56; Ctrl/C9orf72L: 45; Ctrl/C9orf72S: 43; Rab1a/EV: 63; Rab1a/EV/Torin1: 55; Rab1a/C9orf72L: 44; Rab1a/C9orf72S: 37). Rab1a knockdown was confirmed by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228
Rab1a: 5861"
  },
  {
    "caption": "C. SH-SY5Y neuroblastoma cells treated with non-targeting (Ctrl) or Rab1a siRNA were co-transfected with EGFP-LC3 (green) and empty vector (EV), Myc-C9orf72L or Myc-C9orf72S (red). As positive control EV transfected cells were treated for 3 h with Torin1 (250 nM). Autophagosomes were quantified as the number of EGFP-LC3 positive puncta per cell (Mean ± SEM; one-way ANOVA with Fisher's LSD test; ns, not significant; * P ≤ 0.05, *** P ≤ 0.001, **** P ≤ 0.0001; N (cells from 2 independent experiments) = Ctrl/EV: 102; Ctrl/EV/Torin1: 92; Ctrl/C9orf72L: 97; Ctrl/C9orf72S: 76; Rab1a/EV: 102; Rab1a/EV/Torin1: 107; Rab1a/C9orf72L: 101; Rab1a/C9orf72S: 87). Rab1a knockdown was confirmed by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228
Rab1a: 5861"
  },
  {
    "caption": "B. Cell lysates of HEK293 cells co-transfected with Myc-Rab1a and either empty vector, FLAG-C9orf72S or FLAG-C9orf72L were subjected to immunoprecipitation with anti-FLAG antibody. Bound protein was eluted from beads using excess FLAG peptide. Immune eluates were probed for FLAG-C9orf72 and Myc-Rab1a on immunoblots. The input levels of FLAG-C9orf72 and Myc-Rab1a in the transfected cells are shown (Inputs).* indicates remaining Myc-Rab1a signal after reprobing for FLAG-C9orf72.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "C. Cell lysates of HEK293 cells transfected with Myc-C9orf72S or Myc-C9orf72L were subjected to immunoprecipitation with anti-Myc antibody. The resulting immune pellet was probed for endogenous Rab1a.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "D. 35S-radiolabelled recombinant Myc-Rab1a protein loaded with vehicle, GDP or GMP-PNP was added to GST, GST-C9orf72S and GST-C9orf72L immobilized on glutathione-coated beads. 35S-radiolabelled recombinant Myc-Rab1a protein was visualized by autoradiography (top panel). Coomassie-stained GST, GST-C9orf72S and GST-C9orf72L in the pull-down samples are shown (bottom panel). The identity of the Coomassie protein bands was confirmed by mass spectrometry (# = E. coli DnaK Chaperonin; * = E. coli 60kD Chaperonin; Appendix Fig S3). Relative binding of Rab1a to C9orf72 was quantified from 3 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test; ns, not significant; * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001).",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "A. HEK293 cells treated with non-targeting (Ctrl) or C9orf72 siRNA were transfected with HA-ULK1, Myc-Rab1a or HA-ULK1+Myc-Rab1a as indicated. Transfections were laced with mVenus to enable identification of transfected cells for analysis (green). Transfected cells were probed with anti-HA and anti-Myc antibodies and processed for PLA. PLA proximity signals (red) per cell were determined from 3 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, **** P ≤ 0.0001); N (cells) = Ctrl/HA-ULK1: 125, Ctrl/Myc-Rab1a: 149, Ctrl/HA-ULK1+Myc-Rab1a: 163, C9orf72/HA-ULK1: 136, C9orf72/Myc-Rab1a: 133, C9orf72/HA-ULK1+Myc-Rab1a: 155). Scale bar = 20µm.",
    "ncbi_link": "C9orf72: 203228
Rab1a: 5861
ULK1: 8408"
  },
  {
    "caption": "B. HeLa cells treated with non-targeting (Ctrl) or C9orf72 siRNA were co-transfected with mCherry-FIP200 (red) and empty vector (EV) or Myc-Rab1a(Q70L) (green). Translocation of the ULK1 complex was quantified as the number of mCherry-FIP200 positive puncta per cell from 4 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, * P ≤ 0.05, **** P ≤ 0.0001); N (cells) = Ctrl/EV: 101; Ctrl/Q70L: 106; C9orf72/Q70L: 42. C9orf72 knockdown was determined by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228
Rab1a: 5861"
  },
  {
    "caption": "C. HeLa cells treated with non-targeting (Ctrl) or C9orf72 siRNA were co-transfected with EGFP-LC3 (green) and empty vector (EV) or Myc-Rab1a(Q70L) (red). Autophagosomes were quantified as the number of EGFP-LC3 positive puncta per cell (Mean ± SEM; one-way ANOVA with Fisher's LSD test, ** P ≤ 0.01, **** P ≤ 0.0001); N (cells) = Ctrl/EV: 44; Ctrl/Q70L: 32; C9orf72/Q70L: 47. C9orf72 knockdown was determined by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228
Rab1a: 5861"
  },
  {
    "caption": "A. HeLa cells treated with non-targeting (Ctrl) or C9orf72 siRNA were immunostained for endogenous p62. Accumulation of p62 was quantified by counting p62 positive puncta per cell from 3 independent experiments (Mean ± SEM; unpaired t-test, **** P ≤ 0.0001); N (cells) = Ctrl: 74, C9orf72: 55). C9orf72 knockdown was confirmed by RT-qPCR (Appendix Fig S2). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "B. Primary cortical neurons (DIV5) were transduced with 4TU/cell EmGFP non-targeting control miRNA (Ctrl) or C9orf72 miRNA (green); for rescue experiments the cells were additionally transduced with 4TU/cell mVenus-tagged C9orf72s and C9orf72L (verified by immunoblot, Appendix Fig S2). Neurons were immunostained for endogenous p62 3 days post transduction. Accumulation of p62 was quantified by counting p62 positive puncta per soma from 2 independent experiments (Mean ± SEM; one-way ANOVA with Fisher's LSD test, ** P ≤ 0.01; N (cells) = Ctrl miRNA: 80; C9orf72 miRNA: 80; C9orf72 miRNA+C9orf72L+C9orf72S: 75). Scale bar = 10 µm.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "A Heatmap depiction of the 3,731 DNA hypomethylation loci in ago4‐6. Each hypomethylated region corresponds to a colored horizontal bar, and the bars are clustered numerically into a column (y‐axis). Cytosines were examined as CG, CHG, and CHH. The color‐scaled methylation levels indicate the ratios of each type of methylated cytosines over total cytosines of the same type within the examined hypomethylated regions.",
    "ncbi_link": "ago4: 817246"
  },
  {
    "caption": "B Heatmap depiction of the 3,678 DNA hypomethylation loci in ago6‐2.",
    "ncbi_link": "ago6: 817856"
  },
  {
    "caption": "B DNA methylation levels in different mutants. The 2,174 loci where AGO4 and AGO6 are mutually dependent are numerically clustered (y‐axis). Cytosines were examined as CG, CHG, and CHH.",
    "ncbi_link": "AGO4: 817246
AGO6: 817856"
  },
  {
    "caption": "C DNA methylation levels at TAS1a, TAS1c, and TAS3a loci. Snapshots from whole‐genome bisulfite sequencing results are shown.",
    "ncbi_link": "TAS1a: 3767873
TAS1c: 3768717
TAS3a: 3768766"
  },
  {
    "caption": "D RT-qPCR measurements of transposon RNA levels. Double: ago4‐6 ago6‐2 double mutant. Actin 2 was used as an internal control. RNA levels in the mutants are relative to those in the wild‐type (Col‐0). Means ± SD are shown, n = 3.",
    "ncbi_link": "Actin 2: 
ago4: 817246
ago6: 817856"
  },
  {
    "caption": "A AGO6 dysfunction reduces levels of Pol V‐dependent transcripts. RNA levels were measured by RT-qPCR. Means ± SD are shown, n = 3.",
    "ncbi_link": "AGO6: 817856"
  },
  {
    "caption": "B AGO6 dysfunction decreases Pol V occupancy at chromatin of loci where Pol V transcript levels are affected by AGO6. Anti‐NRPE1 antibody was used for ChIP assays. Means ± SD are shown, n = 3.",
    "ncbi_link": "AGO6: 817856"
  },
  {
    "caption": "A Heatmap depiction of the dependence of AGO4‐ and AGO6‐bound siRNAs on Pol IV. Identities of siRNAs were retrieved from Havecker et al (), and siRNAs were grouped into 1,210 AGO4‐bound clusters and 1,486 AGO6‐bound clusters (see Materials and Methods for details), each of which corresponds to a colored horizontal bar; the bars are stacked numerically into a column (y‐axis). Information on siRNA levels in Pol IV mutant and wild‐type plants was retrieved from Zhang et al ().",
    "ncbi_link": "AGO4: 817246
AGO6: 817856"
  },
  {
    "caption": "B Heatmap depiction of the dependence of AGO4‐ and AGO6‐bound siRNAs on Pol V.",
    "ncbi_link": "AGO4: 817246
AGO6: 817856"
  },
  {
    "caption": "C Quantification of individual 24‐nt siRNAs by TaqMan small RNA assays. Double: ago4‐6 ago6‐2 double mutant. snoR101 was used as an internal control. RNA levels in the mutants were relative to those of the wild‐type (Col‐0). Error bars indicate SD, n ≥ 3.",
    "ncbi_link": "snoR101: 
ago4: 817246
ago6: 817856"
  },
  {
    "caption": "(C) Exemplary images of COS-7 cells expressing PEX-mRFP-FKBP before (upper panels) and 30 minutes after (middle panels) rapalog addition in the presence of a translocating motor - KIF1C-MDC-FRB and a non-translocating motor - KIF3B-MDC-FRB. Yellow lines indicate COS7 cell outline. Lower panel represents the overlay of sequential binarized images color coded by time (see also Appendix Figure S1). Scale bar = 20 µm",
    "ncbi_link": "KIF3B: 305967
KIF1C: 10749"
  },
  {
    "caption": "(D) Plots representing intensity time traces of R90% for COS-7 cells transfected with PEX-mRFP-FKBP and KIF1C-MDC-FRB (n =13) or KIF3B-MDC-FRB (n =10). R90% is the radius for each time point that includes 90% of the total fluorescent intensity. Error bars indicate SEM.",
    "ncbi_link": "KIF3B: 305967
KIF1C: 10749"
  },
  {
    "caption": "(A) Representative maximum intensity projections of peroxisome distribution before and after rapalog addition in DIV14 hippocampal neurons expressing PEX-mRFP-FKBP, KIF1C-MDC-FRB, KIF21A-MDC-FRB or KIF5B-MDC-FRB. The morphology of transfected cell is visualized using a BFP fill. Axons are marked with a blue line. Arrows mark peroxisome targeting to dendrites (gray) and axon (blue) 30 min after rapalog addition. Scale bar = 20 µm.",
    "ncbi_link": "KIF1C: 10749
KIF21A: 300158
KIF5B: 3799"
  },
  {
    "caption": "(B) Plots representing intensity time traces of dendrites and axons before and after rapalog addition for KIF1C-MDC-FRB (n = 6 neurons), KIF21A-MDC-FRB (n = 4) and KIF5B-MDC-FRB (n = 8). Traces were normalized to the average intensity before rapalog addition, and to the background.",
    "ncbi_link": "KIF1C: 10749
KIF21A: 300158
KIF5B: 3799"
  },
  {
    "caption": "(E) Percentage of DIV2 neurons transfected with KIF1C-MDC-FRB (n=9 neurons), KIF21A-MDC-FRB (n=14) and KIF5B-MDC-FRB (n=14) in which peroxisomes redistributed into at least 2 neurites after addition of rapalog and (F) Percentage of neurites of DIV2 neurons transfected as in (E) targeted with peroxisomes after addition of rapalog. Error bars indicate SEM; Scale bars: 20 µm.",
    "ncbi_link": "KIF1C: 10749
KIF21A: 300158
KIF5B: 3799"
  },
  {
    "caption": "(C) Representative images of DIV10 hippocampal neurons transfected for 4 days with plasmids encoding β-gal for visualizing the transfected cells and three different DCLK1 shRNAs or DCLK2 shRNA and immunostained for β-gal (red) and DCLK1 (green).",
    "ncbi_link": "DCLK1: 83825
DCLK2: 310698"
  },
  {
    "caption": "(D) Quantitative analysis of normalized average intensity of DCLK1 in regions of interest of DIV10 neurons transfected with DCLK1 sh#1 (n = 16 neurons), DCLK1 sh#2 (n=16) and DCLK1 sh#3 (n=18). Non-transfected cells were taken as a control (n = 48). N=2. Error bars indicate SEM; *** - p < 0.001 (1-way ANOVA followed by a Tukey's Multiple Comparison Test).",
    "ncbi_link": "DCLK1: 83825"
  },
  {
    "caption": "(E) Example of Western blot analysis of protein extracts of DIV4 cortical neurons electroporated on DIV0 with pSUPER (control) or pSUPER encoding one of three DCLK1 shRNAs. Levels of actin were used as an equal loading control.",
    "ncbi_link": "DCLK1: 83825"
  },
  {
    "caption": "(G) Representative maximum projections of peroxisome distribution in DIV14 neurons transfected with PEX-mRFP-FKBP, KIF1C (MDC)-FRB and the indicated shRNA before and 30 minutes after rapalog addition. BFP fill was co-transected to visualize the morphology of transfected neuron. Axons are marked with a blue line. Arrows mark dendrite (gray) and axon (blue) targeting of peroxisomes after rapalog addition. Scale bar = 20 µm",
    "ncbi_link": "KIF1C: 10749"
  },
  {
    "caption": "(H) Quantitative representation of the percentage of DIV14 neurons transfected with PEX-RFP together with either KIF1C, KIF21A or KIF5B and an indicated shRNA. as in (A) in which after addition of rapalog peroxisomes redistributed to axons (\"a\", blue bars), to both axons and dendrites (\"a+d\", red bars) or did not redistribute into any neuronal compartment (\"nt\"-no targeting, gray bars). Per condition 19-44 neurons were analyzed; N = 2.",
    "ncbi_link": "KIF1C: 10749
KIF21A: 300158
KIF5B: 3799"
  },
  {
    "caption": "(H, I) Quantification of run lengths (H) and velocities (I) of vesicles in dendrites of hippocampal neurons transfected at DIV10-14 for 4 days with either NPY-GFP (n = 924 movements) or TfR-GFP (n = 286) or KIF1A-GFP (n = 174) together with a morphology marker BFP. N = 2. Error bars indicate SEM; *** p < 0.001 (1-way ANOVA followed by a Tukey's Multiple Comparison Test ).",
    "ncbi_link": "KIF1A: 363288
NPY: 24604
TfR: 288562"
  },
  {
    "caption": "(K) Representative kymographs of NPY-GFP-labeled dense core vesicle motility in primary dendrites of transfected neurons. DIV10-14 hippocampal neurons were cotransfected, for 4 days, with plasmids encoding NPY-GFP, BFP fill and a KIF21 shRNA mix (n = 30), KIF1shRNA mix (n = 31), KIF1A shRNA (n = 19), KIF1B shRNA (n = 19) or KIF1C shRNA (n = 11). pSUPER was used as a control (n = 15). Scale bar = 5 µm.",
    "ncbi_link": "KIF1A: 363288
KIF1B: 117548
KIF1C: 113886
KIF1: 113886///117548///363288
KIF21: 289397///300158"
  },
  {
    "caption": "(M) Representative kymographs of TfR-GFP-labeled recycling endosome motility in primary dendrites. DIV10-14 Hippocampal neurons were cotransfected with TfR-GFP together with a BFP fill and a KIF1shRNA mix (n = 11). pSUPER was used as a control (n = 20). Scale bar = 5 µm.",
    "ncbi_link": "KIF1: 363288///113886///117548"
  },
  {
    "caption": "(B) Representative kymographs of dense-core vesicle motility in proximal dendrites of transfected neurons. DIV 10-14 hippocampal neurons were co-transfected for 4 days with NPY-GFP and pSUPER (control) or pSUPER encoding DCLK1 shRNA in the absence or presence of DCLK1 truncation constructs and dense core vesicle motility in dendrites was recorded during live-cell imaging. Scale bar = 5 µm.",
    "ncbi_link": "DCLK1: 13175
DCLK1: 83825"
  },
  {
    "caption": "(D, E) DIV10-14 hippocampal neurons were co-transfected for 4 days with either pSUPER (control, n = 20 neurons) or DCLK1 shRNA together with TfR-GFP (n = 16).(D) Representative kymographs of recycling endosome motility in dendrites. Scale bar = 5 µm. (E) Quantification of the average number of recycling endosome entries into dendrites during 50 s of the live recording after photobleaching. Error bars indicate SEM; ns - not significant (Mann-Whitney test). N = 2.",
    "ncbi_link": "DCLK1: 83825
TfR: 288562"
  },
  {
    "caption": "(C, D) Representative image of a COS-7 cell transfected with DCLK1-GFP (C) or DCLK1(ΔKD)-GFP (D) and stained for detyrosinated, tyrosinated or α-tubulin.(E) Representative image of a COS-7 cell transfected with DCLK1-GFP and TagRFP-EB3 and recorded during live-cell imaging. Representative GFP was drawn (over a region marked with white boxes) showing that DCLK1-GFP colocalizes with EB3-TagRFP-T. Scale bars = 20 um.",
    "ncbi_link": "DCLK1: 13175"
  },
  {
    "caption": "(A) Extracts of DIV 7 hippocampal neurons electroporated with pSuper control or with three different DCLK1 shRNAs at DIV0. Samples were analyzed by western blot with indicated antibodies.",
    "ncbi_link": "DCLK1: 83825"
  },
  {
    "caption": "(B, E) Representative images of a hippocampal cell transfected at DIV10 with RFP (to visualize transfected cells), pSUPER (control) or DCLK1 shRNA, fixed at DIV14 and stained for EB3. Black lines indicate the neuronal soma outline. Scale bars = 10 µm.",
    "ncbi_link": "DCLK1: 83825"
  },
  {
    "caption": "(F-I) Hippocampal neurons were co-transfected with MACF18-GFP and pSUPER (control) or DCLK1 shRNA and the dynamics of microtubules in dendrites was traced using life-cell microscopy. (F) Representative kymographs of dynamic microtubules ends growth in dendrites with and without photoablation. Scale bar = 10 µm (C). (G, I) Quantification of the fraction of MACF18 events moving retrogradely and anterogradely in a dendrite before (G) and after (I) photoablation. Eighteen neurons were analyzed per condition; N=2. (H) Scheme of live-cell imaging after photoablation.",
    "ncbi_link": "DCLK1: 83825
MACF18: 362587"
  },
  {
    "caption": "(J, K) Biotin pull-downs (PD) from extracts of HEK293 transfected with biotin-tagged DCLK1 and (J) KIF1A-MDC-HA-FRB, KIF1C-MDC-HA-FRB, KIF5B-MDC-HA-FRB constructs and probed for HA/DCLK1, (K) different GFP-tagged KIF1A truncation constructs and probed for GFP/DCLK1. The ratio input/pellet is 2% for all pull-down experiments.",
    "ncbi_link": "DCLK1: 13175
KIF1A: 547
KIF1C: 10749
KIF5B: 3799"
  },
  {
    "caption": "(L) GFP pull-down from extracts of HEK293 transfected with DCLK1 fragments and KIF1A-MDC-HA-FRB, KIF1C-MDC-HA-FRB and KIF1C-MD-HA and probed for HA/GFP. LacZ-HA was used as a negative control.",
    "ncbi_link": "DCLK1: 13175
KIF1A: 547
KIF1C: 10749"
  },
  {
    "caption": "(A) GFP protein levels in FACS-sorted neonatal (N) and elderly (87y) fibroblasts  transduced with empty (control, -), GFP-MCAK  (+) and GFP-Kif2b  (+) lentiviral plasmids. Tubulin  is shown as loading control.",
    "ncbi_link": "GFP: 
Kif2b: 84643
MCAK: 11004"
  },
  {
    "caption": "(A) Representative images of elderly cells scored as negative (-) or positive (+) for Cdkn1a/p21 (cell cycle inhibitor) and 53BP1  (≥1 foci; DNA damage) senescence  biomarkers. Scale bar 20µm. (B) Percentage of n=cells staining  double-positive for Cdkn1a/p21  and 53BP1  in neonatal (N/N) and elderly (75/87y) human dermal fibroblasts (HDF) transduced with empty, GFP-MCAK  or GFP-Kif2b lentiviral  plasmids. (C) Representative images of elderly cells scored as negative (-) or positive (+) for SA-β-galactosidase (SA-β-gal) activity. Scale bar 20µm. (D) Percentage of n=cells positive for SA-β-gal in neonatal and elderly HDFs  transduced with empty, GFP-MCAK  or GFP-Kif2b lentiviral  plasmids. Data Information: Values are mean ± s.d. of at least two independent experiments. ns p>0.05, *** p<0.001, **** p<0.0001 by two tailed chi-square test (B,D).",
    "ncbi_link": "GFP: 
Kif2b: 84643
MCAK: 11004"
  },
  {
    "caption": "E. Average expression level of the genes Fas3 (left panel) and zfh1 (right panel) used as markers to assign epithelial and myoblast cells, respectively, in the reference dataset.",
    "ncbi_link": "Fas3: 35097
zfh1: 43650"
  },
  {
    "caption": "H. Confocal single plane image of third instar larval wing disc and orthogonal view of SPARC>GFP (green) stained with anti-Ct (red) and 4´,6-diamidino-2-phenylindole (DAPI, blue). Full genotype y-, w-/w-; UAS-GFP/+; SPARC-GAL4/+.",
    "ncbi_link": "GFP: 
GAL4: 855828
SPARC: 43230"
  },
  {
    "caption": "D. Average expression level of the genes used as known markers to assign each epithelial cluster in the reference atlas dataset. Cells colored by the expression of nub, wg, zfh2, Sox15, grn, bnl, eyg, Ance, Idg4 and drm.",
    "ncbi_link": "Ance: 34805
bnl: 42356
drm: 49638
eyg: 39419
grn: 40962
nub: 34669
Sox15: 36575
wg: 34009
zfh2: 43795"
  },
  {
    "caption": "F. Confocal single plane image of third instar larval wing disc stained with anti-Nub, anti-Wg, anti-Svp, anti-Hairy (red), reporting expression of dpp-lacZ, Dad-lacZ (anti-β-gal, red) and counterstained with DAPI (cyan). Scale bars: 100 μm. Full genotypes: P{CaryP}attP2 (top and bottom panels), P{PZ}dpp[10638];+, and y- w-;+; P{lacW}Dad[j1E4].",
    "ncbi_link": "Dad: 42059
dpp: 33432"
  },
  {
    "caption": "Confocal single plane images of third instar larval wing discs stained with: (C) anti-Ct (red) and anti-Zfh1 (green), (D) kirre[rp298]-lacZ (anti-β-gal, green) and anti-Zfh1 (red), (E) Ten-a[MI04411]::GFP (green), anti-Ct (red) and anti-Zfh1 (cyan), (F) anti-Nrt (red) and anti-Zfh1 (cyan), (G) Argk[CB3789]::GFP (green), anti-Ct (red) and anti-Zfh1 (cyan), (H) nkd[MI00209]::GFP (green), anti-Ct (red) and anti-Zfh1 (cyan), (I) Ama[NP1297]>GFP (green), anti-Ct (red) and anti-Zfh1 (cyan) and (J) Mef2>CD8-GFP (green), and fluorescent in situ hybridization of Ama-RNA probe (white).",
    "ncbi_link": "Ama: 40831"
  },
  {
    "caption": "Confocal single plane images of third instar larval wing discs stained with: K. Ama[NP1297]>gTRACE showing the lineage of Ama-GAL4 (green) and the active GAL4 (red), and fluorescent in situ hybridization of Ama-RNA probe (white). L. Confocal single plane images of adult DFM of Ama[NP1297]>gTRACE showing the lineage of Ama-GAL4 (green) and the active GAL4 (red) stained with DAPI (white) dorsal right, anterior up. DFM are numbered in white following (Lawrence, 1982). ",
    "ncbi_link": "Ama: 40831
GAL4: 855828"
  },
  {
    "caption": "The muscle-specific 151-GAL4 drivers were crossed to UAS-RNAi lines to knockdown the expression of the gene markers for the myoblast clusters. C). Viability test quantified by scoring the percentage of viable animals at each developmental stage, including early pupa (black), pharate (grey) and adult (white), relative to the total number of animals. Data are expressed as stacked bars showing the median with interquartile range (n≥ 3 independent biological replicates), unless noted as viable (NQ) and lethal (NQ), which stands for animals that were viable and lethal, respectively, but no quantitative analysis were performed. D). Flight ability scored by quantifying the percentage of flies landing on each section of the column (top, middle and bottom) as indicated on the diagram on the right. Data are expressed as stacked bars. The total number of flies used in each assay was pooled together and displayed next to each bar (N≥6). n/a stands for non-applicable since animals are not viable.",
    "ncbi_link": "GAL4: 855828"
  },
  {
    "caption": "E. Confocal single plane images of third instar larval wing discs from Mef2>mCherry-RNAi, (left panel) and Mef2>chinmo[HM04048]-RNAi (right panel) stained with anti-Zfh1 (red) and DAPI (cyan). Scale bars: 50 μm. F. Quantification of phenotype displayed in (E). Stacked bars showing the percentage of wing discs scored as either normal or as abnormal. Data are expressed as mean ± sem, N = 32 discs per genotype, n = 3 independent experiments. ",
    "ncbi_link": "mCherry: 
chinmo: 33343
Mef2: 36032"
  },
  {
    "caption": "G. Quantification of viability test. Since the UAS-Ama-RNAi[GD12733] transgene is inserted on Chromosome X the genotype of females is Mef2>Ama-RNAi whereas males are Mef2>+. Box plot showing the ratio of flies with genotype of interest (females) over control flies (males). The whiskers show 5-95 percentile, and the middle line the median. * p=0.014 (Mann-Whitney test, N≥6 independent biological replicates). Full genotypes are w, UAS-Dicer2;+; mCherry-RNAi/Mef2-GAL4 and w, UAS-Dicer2, UAS-Ama-RNAi[GD12733];+; Mef2-GAL4.",
    "ncbi_link": "mCherry: 
Ama: 40831
Dicer2: 36993
GAL4: 855828
Mef2: 36032"
  },
  {
    "caption": "A. Lethality of 1151>Ama-RNAi[HMS00297] animals at pharate stage was partially rescued by overexpressing the transgene Ama-cDNA. Representative images of adults and pharate pupa are shown. Full genotypes: 1151-GAL4;UAS-myrRFP;+ , 1151-GAL4;UAS-myrRFP;UAS-Ama[HMS00297]-RNAi , 1151-GAL4;UAS-AmaOE/CyO;UAS-Ama[HMS00297]-RNAi and 1151-GAL4;UAS-AmaOE;+.",
    "ncbi_link": "CyO: 
myr: 
RFP: 
Ama: 40831
GAL4: 855828"
  },
  {
    "caption": "C. Average expression level of the genes Fas3 (left panel) and zfh1 (right panel) in the 1151>Ama-RNAi dataset.",
    "ncbi_link": "Ama: 40831
Fas3: 35097
zfh1: 43650"
  },
  {
    "caption": "D. Confocal single plane images of 1151>mCherry-RNAi and 1151>Ama-RNAi wing discs stained with anti-Ct (red) and anti-Zfh1 (green).",
    "ncbi_link": "mCherry: 
Ama: 40831"
  },
  {
    "caption": "E. Dot plots showing the expression levels of the top markers for myoblast clusters identified in the reference cell atlas across the cluster of myoblasts in 1151>Ama-RNAi and 7 myoblast clusters in control dataset.",
    "ncbi_link": "Ama: 40831"
  },
  {
    "caption": "F. The myoblast cells in 1151>Ama-RNAi dataset projected into the reference single cell atlas by transferring cell type labels using Seurat. The bar graph represents the total number of cells in each cluster normalized to the total number of epithelial cells per genotype.",
    "ncbi_link": "Ama: 40831"
  },
  {
    "caption": "G-H. Confocal single plane images of 1151>mCherry-RNAi and 1151>Ama-RNAi wing discs stained with anti-Zfh1 (green) and (G) anti-Nrt (white) at wandering third instar larval stage (110 - 135 h AEL) or (H) DAPI (red) at early third instar larval wing discs (72 - 110 h AEL).",
    "ncbi_link": "mCherry: 
Ama: 40831"
  },
  {
    "caption": "Confocal single plane images of 1151>Ama-RNAi animals and 1151>mCherry-RNAi. A. Forming DFM at 40 h APF stained with anti-Zfh1 (green), anti-Futsch (22c10, red) and anti-Kettin (white). White arrows point to the wing hinge, wings pointing left, anterior up. B. Forming IFM (DLM) at 16 h APF, stained with anti-Futsch (22c10, red), anti-Zfh1 (green) and DAPI (cyan). Yellow-dashed box indicates magnified area (bottom panel). Anterior up.",
    "ncbi_link": "mCherry: 
Ama: 40831"
  },
  {
    "caption": "G-K Same as B in WT MEF, in cells exposed to 20 mM CST and in Cnx-, Crt- and ERp57-KO MEF. L Quantification of ATZ-positive EL (n=10, 9, 11, 10, 11 cells, respectively). One-way ANOVA and Dunnett's multiple comparisons test, ns P>0.05, **** P<0.0001. Data information: Scale bars: 10 μm. ",
    "ncbi_link": "Crt: 12317
Cnx: 12330
ERp57: 14827"
  },
  {
    "caption": "A HEK293 cells transfected with empty vector (lanes 1, 6), ATZ-HA (2, 7), FAM134B-V5 (3 and 8), FAM134B-V5 and ATZ-HA (4, 9), or FAM134BLIR-V5 and ATZ-HA (5, 10), incubated for 12 h with 50 nM BafA1 and then treated with the cross-linker DSP before lysis as described in Methods. Lanes 1-5, WB of the total cell extract (TCE); lanes 6-10, WB of antiV5 immunoprecipites to isolate complexes containing ectopically expressed FAM134B or FAM134BLIR. The membranes were probed with antiV5 (upper panels), antiCNX, antiHA and antiLC3 antibodies. B Quantification of LC3 co-precipitating with FAM134B-V5 (A, lanes 8 and 9). Mean ± SEM, n=3, unpaired two-tailed t-test, * P<0.05. ",
    "ncbi_link": "HA: 
V5: 
FAM134B: 66270
ATZ: 5265"
  },
  {
    "caption": "WT MEF. Scale bar: 10 μm. D Ectopic expression of FAM134BLIR in WT MEF inhibits ATZ delivery to endolysosomes. Scale bar: 10 μm. ",
    "ncbi_link": "FAM134B: 66270"
  },
  {
    "caption": "E, F Distribution of gold-labeled ATZ-HA by IEM in BafA1 treated WT MEF and WT MEF overexpressing FAM134BLIR, respectively. EV, ER-derived vesicles, red arrowheads; EL, endolysosome. G Quantification of ATZ-gold density of E, F (n=75 and 79 EL, respectively). Unpaired two-tailed t-test, **** P <0.0001. ",
    "ncbi_link": "FAM134B: 66270"
  },
  {
    "caption": "I Decay of ATZ polymers (CHX chase, upper panel) immunoisolated with the polymer-specific 2C1 antibody (visualized with antiHA in WB) in HEK293 cells mock-transfected (lanes 1-4) or expressing FAM134BLIR-V5 (lanes 5-8). Middle panel, expression of FAM134BLIR-V5 assessed by WB; lower panel, loading control. (J) Quantification of (I) (Mean ± SEM, n=3, unpaired two-tailed t-test, * P<0.05). ",
    "ncbi_link": "V5: 
FAM134B: 66270"
  },
  {
    "caption": "K Flow cytometry analysis of ATZ-HA polymer levels in MEFs mock treated, exposed to BafA1, and co-expressing FAM134LIR. MFI: mean fluorescence intensity (Mean ± SEM, n=5, unpaired two-tailed t-test, ns P>0.05, ** P<0.01, *** P <0.001).",
    "ncbi_link": "FAM134: "
  },
  {
    "caption": "A WB analysis showing KO efficiency for CRISPR134B MEF.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "WB analysis showing KO efficiency for CRISPR62 MEF.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "C-E CRISPR WT MEF, CRISPR134B MEF, CRISPR62 MEF, respectively. Scale bars: 10 μm. F Quantification of C-E (n=10, 8, 7 cells, respectively). One-way ANOVA and Dunnett's multiple comparisons test, ns P>0.05, **** P<0.0001. ",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "A-H Intracellular localization of LAMP1-positive EL, total (HA) and polymeric (2C1) ATZ in WT MEF exposed to BafA1 for 12 h (A); in Atg4BKO MEF (B); in Atg7KO MEF (C); in Fip200KO MEF (D); in Ulk1/2 double-KO MEF (E); in Atg13KO MEF (F); in Atg9KO MEF (G); in RubiconKO MEF (H). Scale bars: 10 μm. I Quantifications of A-H (n=10, 9, 9, 10, 7, 15, 9, 12 cells). One-way ANOVA and Dunnett's multiple comparisons test, ns P>0.05, **** P<0.0001. ",
    "ncbi_link": "Atg13: 51897
Atg4B: 66615
Atg7: 74244
Atg9: 245860
Fip200: 12421
Rubicon: 100502698
Ulk1: 22241"
  },
  {
    "caption": "A KO efficiency in CRISPR17 MEF.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "KO efficiency in CRISPR8.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "C-E CLSM analysis of ATZ delivery to LAMP1-positive endolysosomes in BafA1-treated CRISPRWT MEF (C); in CRISPR17 MEF(D); in CRISPR8 MEF (E). Scale bars: 10 μm.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "G-I Distribution of gold-labelled ATZ-HA by IEM in CRISPRWT MEF exposed to BafA1 (G); in CRISPR17 (H); in CRISPR8. (I). ER, endoplasmic reticulum; EV, ER-derived vesicles; EL, endolysosomes. Scale bars: 1 μm.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "GFP reconstitution in ATZ-HA transfected CRISPR17 MEF expressing FAM134B-T11 and GFP1-10-LC3. Scale bar: 10 μm. K Same as J by CLEM. ATZ-HA staining in red, LAMP1-positive endolysosomes in cyan. FAM134B:LC-induce GFP reconstitution in green. FAM134B in gold is shown. Scale bar: 1 μm.",
    "ncbi_link": "CRISPR: 
GFP: 
HA: 
ATZ: 5265"
  },
  {
    "caption": "(i-q) End phase of rod death was assessed by section analysis (i-l) or by retinal flat mounts (m-q). In the Rho−/− mouse, the onset of rod death was around PW5 (a) and progressed up to PW25 (l). By PW17, the ONL was reduced to one row of cells (h, j) and the remaining rods died in the following 8 weeks (j-q), as seen by immunofluorescence with an antibody to Gnat1 on sections of progressively older animals (j-l). Retinal flat mounts showing rods visualized by immunofluorescence microscopy with an antibody Gnat1 are shown in m-q. The entire retina is shown in m, higher magnifications around the optic nerve head are shown in n and o, and the peripheral region is shown in p. No signal was seen at PW25 on flat mounts (q) or sections (l). Age (in PW) is indicated in the panels. Vertical bar in a-c and e-l indicates thickness of the ONL.",
    "ncbi_link": "Rho: 212541"
  },
  {
    "caption": "(a) qRT-PCR analysis for Opn1sw during cone degeneration.",
    "ncbi_link": "Opn1sw: 12057"
  },
  {
    "caption": "(b-o) All panels show retinal flat mounts except for i and l. Green signal indicates PNA expression and red signal indicates red/green or blue opsin. The wild-type retina is shown at P35 in b-d. Red/green opsin (b) and PNA (c, d) expression were detected both dorsally and ventrally, whereas blue opsin (c,d) was detected only ventrally. The Pde6b−/− mouse is analyzed in e-g and j-o. A central to peripheral gradient of PNA and shortening of cone outer segments is shown in e-g. At P20, there were fewer elongated outer segments in the center (e) as compared with the periphery. Higher magnifications of a central or peripheral outer segment from e are shown in f and g, and a wild-type outer segment is shown in h (white line marks the outer segment). A quantification of outer segment length at 3 weeks is shown in i (error bars represent s.d. of 15 measurements each). With the shortening of outer segments during degeneration, red/green opsin was localized throughout the membrane of the cell body, and PNA, which detects an extracellular protein(s), was reduced to a small dot attached to the residual outer segment (j) (yellow shows red/green and PNA overlap, arrow). A higher magnification of a cone showing red/green at the membrane is displayed in k (arrow). A cross section showing red/green in cell body is shown in l (arrows) (P70; j-l). During degeneration, red/ green opsin was detected mainly dorsally (m), whereas PNA (m, n) or blue opsin (o) expression were not altered (m and n, P21; o, P49). GCL, ganglion cell layer; INL, inner nuclear layer.",
    "ncbi_link": "Pde6b: 18587"
  },
  {
    "caption": "(h-m) Reduced levels of dorsal P-mTOR during photoreceptor degeneration (red). The wild-type control is shown in h and the Pde6b mutant is shown in i and j. Reduction started during rod death at P15 (i) as the outer segments (green, PNA) detached from the retinal pigmented epithelium. By P30, only a few cones (green signal: α-β-galactosidase) showed high levels of P-mTOR (red) (j). (k-m) Similar reduction was seen in dorsal cones of the other three mutants (cones marked in green by PNA; Pde6g−/− is shown at P35 in k; Rho−/− is shown at PW20 in l; P23H is shown at PW70 in m). All panels show immunofluorescence microscopy on retinal flat mounts (photoreceptor side up) with the exception of b, c and g, which show retinal sections. Blue indicates DAPI.",
    "ncbi_link": "Pde6b: 18587
Pde6g: 18588
Rho: 212541"
  },
  {
    "caption": "All panels show immunofluorescent staining. Blue shows nuclear DAPI staining and green shows cones marked with PNA. (a-f) Staining for HIF-1α (red signal). (a) Wild type (PW10) stained for HIF-1α (inset shows higher magnification). (b, c) Cross sections in wild type stained for HIF-1α (PW10). DAPI overlap is shown in c. (d-f) During cone degeneration in Pde6b−/− (PW10) mice, we found increased levels of HIF-1α in cones (inset in d shows higher magnification with DAPI overlap). Cross sections indicated that the increase of Hif-1α occurred mainly in cones (arrows point to cones that are located in the top layer of the inner nuclear layer at this stage; e). DAPI overlap is shown in f.",
    "ncbi_link": "Pde6b: 18587"
  },
  {
    "caption": "(a-c) Immunofluorescence microscopy on retinal flat mounts (LAMP-2 is shown in green, red/green opsin in red and DAPI in blue). Insets show enlarged cells (arrow). A wild-type retinae at PW5 showing a lysosome (small green dots) with normal LAMP-2 distribution is imaged in a. Weak red/green opsin signal was detected at the level of the photoreceptornuclei, as it was mainly found in the outer segments in the wild type. Enlarged lysosomes (dots) resulting from an accumulation of LAMP-2 at the lysosomal membrane were seen specifically in cones from Pde6b−/− micePW5 (b). Confocal section of same field as in b taken at the level of the inner nuclear layer showed LAMP-2 levels similar to those in wild type (c).",
    "ncbi_link": "Pde6b: 18587"
  },
  {
    "caption": "(d) qRT-PCR for the three different LAMP-2 splice forms showing the relative concentration and the ratios between the Pde6b−/− mutant and wild type. Error bars represent s.d. of three measurements.",
    "ncbi_link": "LAMP-2: 16784
Pde6b: 18587"
  },
  {
    "caption": "(a-c) Retinal flat mounts of Pde6b−/− mutants at PW7 stained for LacZ to detect cones (see Methods and Supplementary Fig. 9). An example of untreated control is shown in a, an example of a mouse injected with streptozotocin is shown in b and an example of a mouse injected daily with insulin is shown in c. (d) Quantification of cone survival after four weeks of treatment. Data represents an average of at least eight retinae. The y axis represents the percentage of the cone surface area versus the surface area of entire retina (see Supplementary Figs. 8 and 10).",
    "ncbi_link": "Pde6b: 18587"
  },
  {
    "caption": "(g, h) Immunofluorescence microscopy staining on retinal flat mounts for HIF-1α (red) and PNA (green) in untreated control Pde6b−/− (g) and Pde6b−/− mice treated for 4 weeks with insulin (h). DAPI is shown in blue. Error bars in d-f represent s.d.",
    "ncbi_link": "Pde6b: 18587"
  },
  {
    "caption": "Real-time qRT-PCR analysis of C/EBPβ mRNA in CD4+ naïve T cells inactivated (naive) or cultured for 24 hr under conditions as indicated with DMSO or ATRA (all-trans retinoic acid). Data are representative of two independent experiments with consistent results and normalized with β-actin (mean and s.e.m. of quadruplicates)",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPζ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean value from 8(C are shown on the right Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate",
    "ncbi_link": "C/EBP: 12611///12608///12607///110794///12606///12609
C/EBPζ: 12607"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPζ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean values fro 6(D are shown on the right. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate",
    "ncbi_link": "C/EBP: 110794///12611///12607///12609///12608///12606
C/EBPζ: 12607"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPζ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean values fro E 7(F are shown on the right. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate",
    "ncbi_link": "C/EBP: 110794///12611///12607///12609///12608///12606
C/EBPζ: 12607"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding C/EBPβ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the upper panel and pooled data from 4 (A are shown in the bottom. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate. Error bars represent mean ± s.e.m",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding C/EBPβ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the upper panel and pooled data fro ), 3 (B are shown in the bottom. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate. Error bars represent mean ± s.e.m",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "Real-time qRT-PCR analysis of FACS-sorted GFP+ cells from CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding C/EBPβ and cultured for 2 d in the conditions as indicated. Data are representative of two independent experiments with consistent results and normalized with β-actin (mean ± s.e.m. of triplicates)",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "Body weight of RAG-2-/- mice after transfer with 5 x 105 CD4+CD45RBhigh cells alone (circles) or with 2 x 105 FACS-sorted CD4+GFP+ cells transduced with control retrovirus (MigRI) (squares) or retrovirus encoding C/EBPβ (triangles) and cultured for 2 d in the presence of TGF-β and culture supernatant. Each time point contains three (circles) or four (squares and triangles) mice in each group. Error bars represent mean ± s.d",
    "ncbi_link": "C/EBPβ: 12608
CD45RB: 19264
RAG-2: 19374"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining of mesenteric lymph node cells of Balb/c mice that received RAG2-/-DO11.10 CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding A-C/EBP or C/EBPβ. (A) The recipients were immunized via intravenous injection of OVA323-339 peptide (20 ug) 1 and 3 d after transfer of transduced cells and analyzed 5 d after the first immunization. (B) The recipients were fed 1% OVA solution in drinking water for 5 consecutive days. Representative experiments are shown in the left panel and pooled data from 4 (A) or 3 (B) independent experiments with mean values are shown on the right. Dot plots are gated for CD4+KJ.1.26+GFP+ (top) or CD4+KJ.1.26+GFP- (bottom) and numbers indicate percent Foxp3+ cells in the gate. Statistical analysis was performed using one-way ANOVA. (*p<0.05, **p<0.01; ns, not significant",
    "ncbi_link": "C/EBPβ: 12608
C/EBP: 110794///12607///12608///12611///12609///12606
RAG2: 19374"
  },
  {
    "caption": "EMSA of nuclear extracts of Jurkat cells transfected with indicated expression vectors and assessed with a probe covering the putative unmethyl- or methyl-CRE sequence in the TSDR",
    "ncbi_link": "CRE: "
  },
  {
    "caption": "ChIP-qPCR assay of C/EBPβ on the Foxp3 TSDR in naïve CD4+ T cells cultured for 2 d under conditions as indicated. Data are representative of two independent experiments with consistent results (mean ± s.e.m. of triplicates)",
    "ncbi_link": "Foxp3: 50943"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding C/EBPβ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data from 4 (C with mean values are shown on the right. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate",
    "ncbi_link": "C/EBPβ: 1051"
  },
  {
    "caption": "Flow cytometry of intracellular Foxp3 staining in CD4+ naïve T cells transduced with control retrovirus (MigRI) or retrovirus encoding C/EBPβ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data fro 5 (D are shown on the right. Dot plots are gated for CD4+GFP+ and numbers indicate percent Foxp3+ cells in the gate",
    "ncbi_link": "C/EBPβ: 1051"
  },
  {
    "caption": "CD4+ naïve T cells from Foxp3EGFP mice were transduced with control retrovirus (MIN) or retrovirus encoding C/EBPβ (MIN-C/EBPβ) and stimulated with anti-CD3 and anti-CD28 for 2 d in the presence of TGF-β, anti-IFN-γ and anti-IL-4 Abs. GFP+(Foxp3+) hNGFR+ T cells were sorted to high purity (0 hr) and restimulated with anti-CD3 and anti-CD28 for 2 d in the presence of IL-4, IL-6, IL-12 or none. Foxp3 expression was assessed based on GFP expression. Data are representative of two independent experiments with consistent results",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "Flow cytometry of CFSE-labeled CD45.1+CD4+ T cells stimulated 3 d alone or together with CD45.2+GFP(Foxp3)+NGFR+-sorted CD4+ naïve T cells from Foxp3EGFP mice transduced with control retrovirus (Min) or retrovirus encoding C/EBPβ and cultured for 3 d in the presence of TGF-β, anti-IFN-γ and anti-IL-4 Abs. Histograms are gated for CD45.1+. The ratios shown are responder to suppressor. Data are representative of two independent experiments with consistent results",
    "ncbi_link": "C/EBPβ: 12608"
  },
  {
    "caption": "EAE disease course of RAG2-/- mice that received CD45.1+2D2CD4+ naive T cells alone or together with CD4+GFP/Foxp3+ iTreg cells from CD45.1-2D2CD4+GFP(Foxp3)+ naïve T cells transduced with either control retrovirus (MIN) or retrovirus encoding C/EBPβ, cultured in the presence of TGF-β, anti-IFN-γ and anti-IL-4 Abs and sorted based on GFP/Foxp3 expression. The recipients were immunized with myelin oligodendrocyte glycoprotein peptide (100 ug) 1 d after transfer. Data show mean ± s.e.m of the EAE clinical score of 9 (day 1 to day 11), 5 (day 12 to day 16) or 4 (day 17 to day 20) mice of each group",
    "ncbi_link": "C/EBPβ: 12608
RAG2: 19374"
  },
  {
    "caption": "Body weight of RAG-2-/- mice after transfer with 5 x 105 CD45.1+CD4+CD45RBhigh cells alone (circles) or with 2 x 105 FACS-sorted CD45.1-CD4+GFP(Foxp3)+NGFR+ cells transduced with control retrovirus (Min)(filled rectangles) or retrovirus encoding C/EBPβ (empty rectangles) and cultured for 2 d in the presence of TGF-β, anti-IFN-γ and anti-IL-4 Abs. Each time point contains three mice in each group. Error bars represent mean ± s.e.m",
    "ncbi_link": "C/EBPβ: 12608
RAG-2: 19374"
  },
  {
    "caption": "Flow cytometry of intracellular FOXP3 staining (right) or isotype control (left) in human CD4+CD25-CD45RA+ naïve T cells transduced with control retrovirus (Min) or retrovirus encoding hC/EBPβ and cultured for 2 d under conditions as indicated. Representative experiments are shown in the left panel and pooled data with mean±s.e.m are shown on the right. Histograms are gated for CD4+NGFR+. Statistical analysis was performed using unpaired two-tailed t test. (*p<0.05; ns, not significant)",
    "ncbi_link": "hC/EBPβ: 1051"
  },
  {
    "caption": "Flow cytometry of CFSE-labeled human CD4+CD25- T cells (responder) stimulated 4 d alone or together with NGFR+-sorted human CD4+CD25-CD45RA+ naïve T cells (suppressor) transduced with control retrovirus (Min) or retrovirus encoding hC/EBPβ and cultured for 5 d in the presence of hTGF-β, anti-hIFN-γ and anti-hIL-4 Abs. Histograms are gated for CFSE+. The ratio of responder to suppressor is 1:0.2 (top) or 1:0.4(bottom). Data are representative of two independent experiments with consistent results",
    "ncbi_link": "hC/EBPβ: 1051"
  },
  {
    "caption": "(e) Gene Set Enrichment Analysis (GSEA) of the genes differentially expressed between YAP/TAZ-deficient (siY/T) and control siRNA (siCtrl) transfected HLE cells showed an enrichment for genes involved in the regulation of lipid peroxidation.",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(g) Basal lipid peroxidation levels increased with the loss of function of YAP/TAZ. HLE-shLuc and HLE-shY/T cells were stained with C11-BODIPY 581/591. Reduced-Bodipy  was measured by flow cytometry  using a 488  nm laser, and oxidized-Bodipy was measured with a  561 nm laser. A significant shift of oxidized-Bodipy occurred upon depletion of YAP/TAZ. Results represent three independent experiments.",
    "ncbi_link": "Luc: 
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(b) Quantitative RT-PCR analysis confirmed the dependency of SLC7A11 gene expression on YAP/TAZ. HLE  cells were transfected with control siRNA (siCtrl) or siRNA against  YAP/TAZ (siY/T) and cultured with DMSO  or 6μM Sorafenib for 18 hours. RNA was extracted and analyzed by quantitative RT-PCR. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using one-way ANOVA. Results represent three independent experiments.",
    "ncbi_link": "SLC7A11: 23657
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(f)  Binding of YAP and  TAZ to a DNA fragment containing the TEAD binding motif in the SLC7A11  promoter. ChIP  was performed on  HLE cell lysate with antibodies against  YAP and TAZ  and rabbit IgG as control. DNA fragments were amplified using the primers specific for TEAD binding motif in the SLC7A11  promoter region shown in (e). The non-coding region NC10  served as negative control, and the bona fide  TEAD target gene  CYR61 served as positive control. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using one-way ANOVA. Results represent three independent experiments.",
    "ncbi_link": "NC10: 
CYR61: 3491
SLC7A11: 23657"
  },
  {
    "caption": "(a) SLC7A11  protein levels decreased upon siRNA-mediated depletion of ATF4 but not of NRF2  either with or without Sorafenib treatment, and Sorafenib promoted the expression of ATF4. HLE cells were transfected with siCtrl, siATF4 or siNRF2 and treated with or without 6μM Sorafenib for 18 hours. The expression  of SLC7A11, ATF4  and NRF2 was determined by  immunoblotting. GAPDH served as loading control. Results represent three independent experiments.",
    "ncbi_link": "ATF4: 468
NRF2: 4780"
  },
  {
    "caption": "(f) Colony formation assay demonstrating that the ferroptosis  inhibitor Ferrostatin-1 (Fer) reversed Sorafenib-induced cell death in ATF4-deficient HCC cells. HLE cells transfected with siCtrl or siATF4 were treated with Sorafenib (8μM) or DMSO plus either DMSO or Ferrostatin-1 (Fer; 5μM) for 2 weeks. Results represent three independent experiments.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "(g) The forced expression of SLC7A11 rescued cell death induced by  ATF4 ablation. HLE cells were transfected with a construct coding for SLC7A11 (SLC7A11 OE) or empty vector (EV) and with siCtrl or siATF4 every other day. Cells were then treated with either DMSO or 6μM Sorafenib for 2 weeks. Colony formation  was visualized by  crystal violet staining. Results represent three independent experiments.",
    "ncbi_link": "ATF4: 468
SLC7A11: 23657"
  },
  {
    "caption": "(a) YAP/TAZ deficiency repressed Sorafenib-induced expression of ATF4, whereas ATF4  depletion had no effect on YAP/TAZ protein levels. HLE  cells were transfected with siCtrl or siATF4 or siY/T and treated with 6μM Sorafenib or not for 18 hours. ATF4 and YAP/TAZ protein levels were analyzed by immunoblotting. GAPDH served as loading control. Results represent three independent experiments.",
    "ncbi_link": "ATF4: 468
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(b) Quantitative RT-PCR analysis verified that depletion of YAP/TAZ  or ATF4 declined the expression  levels of SLC7A11 and CHAC1. HLE cells were transfected with siCtrl, siY/T or siATF4 and cultured with 6μM Sorafenib  for 18 hours.  Quantitative RT-PCR was conducted to determine SLC7A11 and CHAC1  mRNA levels. Data are shown as mean ± standard deviation (SD).Statistical significance was calculated using Two-way ANOVA. Results represent 3 independent experiments.",
    "ncbi_link": "ATF4: 468
CHAC1: 79094
SLC7A11: 23657
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(e) Binding of YAP and TAZ to DNA fragments containing the AARE binding  motif in the SLC7A11  promoter. ChIP was performed on HLE cell lysate with antibodies against  YAP and TAZ and rabbit IgG as control. DNA fragments were amplified using the primers specific for AARE binding motif in the SLC7A11 promoter region. The non-coding region  NC10 served as negative control, and the bona fide   TEAD  target genes  CYR61 and ANKRD1 served as positive controls. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using one-way ANOVA. Results represent three independent experiments.",
    "ncbi_link": "NC10: 
ANKRD1: 27063
CYR61: 3491
SLC7A11: 23657"
  },
  {
    "caption": "(g) YAP/TAZ bind to DNA fragments containing the AARE binding motif within the SLC7A11  promoter via ATF4. HLE cells were cultured with 6μM Sorafenib for 18 hours before harvest. In a 1st round ChIP ATF4 was  immunoprecipitated  with antibody against  ATF4, rabbit IgG was used as control. DNA-protein immunocomplexes were eluted and in a 2nd round ChIP antibody against  YAP/TAZ was used to precipitate DNA fragments which were then amplified and analyzed by quantitative PCR for the  AARE motif in the SLC7A11 promoter. NC10  served as negative PCR control. Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using one-way ANOVA. Results represent three independent experiments.",
    "ncbi_link": "NC10: 
SLC7A11: 23657"
  },
  {
    "caption": "Combination of  YAP/TAZ deficiency and Sorafenib treatment suppressed tumor growth in a HCC xenograft  model. SNU398-shLuc or SNU398-shYAP/TAZ (shY/T) cells were transplanted into the flanks of immunodeficient NSG mice. Once the tumors were palpable, mice were treated with 20mg/kg Sorafenib  or vehicle control, and tumor sizes were measured twice a week (b).  Tumor weights were also recorded after sacrifice of the mice Data are shown as mean ± standard deviation (SD). Statistical significance was calculated using two-way ANOVA analysis. Mouse numbers of shLuc + Vehicle, shY/T + Vechicle and shY/T + Srf  were 4 per cohort, mouse numbers of shLuc + Srf  were 3 per cohort.",
    "ncbi_link": "Luc: 
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "(D) Binding of FITC-labelled peptides P2 and CP2 to wild-type pneumococci, TIGR4 (T4) and isogenic PLY mutant (T4Δply) was visualized by fluorescence microscopy. Scale bars, 10 μm. In magnified images, scale bars, 1 μm. Images are representative of three independent experiments.",
    "ncbi_link": "PLY: 
ply: "
  },
  {
    "caption": "(E) The hemolytic activity of wild-type pneumococci, TIGR4 (T4) and PLY mutant, T4Δply in the presence of 100 μM peptide P2 and CP2. Data are the mean ± s.e.m. of three independent experiments. *** denotes P < 0.001 by one-way ANOVA with Bonferroni post hoc test for multiple comparisons. n.s. denotes not significant. Exact P values are shown in Appendix Table S4.",
    "ncbi_link": "ply: 
PLY: "
  },
  {
    "caption": "(D) Invasion of wild-type pneumococci T4 (TIGR4) or its isogenic PLY mutant T4Δply into the lung epithelial models (n=3/condition) in the presence or absence of 100 μM peptide P2 or the control peptide CP2 at 2h post infection was measured using CFU viability assay following gentamicin killing of extracellular bacteria. Anti-PLY was used as control to test the effect of blocking PLY. Data in d and e are mean ± s.e.m. of n=3 models/condition from two independent experiments. % bacterial entry = (bacteria uptaken/input) x100. ** denotes P < 0.01 by one-way ANOVA with Dunnett's post hoc test for multiple comparisons. n.s. denotes not significant. Exact P values are shown in Appendix Table S4.",
    "ncbi_link": "ply: 
PLY: "
  },
  {
    "caption": "(A) Survival percentage of 3-4 dpf zebrafish embryos (n ≥156) upon infection with S. pneumoniae T4 alone or its isogenic PLY mutant, T4Δply. Injection with E3 growth medium served as mock control. *** denotes P < 0.0005 and **** denotes P < 0.0001 by Mantel Cox test. Exact P values are shown in Appendix Table S4.",
    "ncbi_link": "PLY: 
ply: "
  },
  {
    "caption": "(C) Survival of mice (n=10) upon intranasal infection with 2x106 CFU of S. pneumoniae T4 together with peptide P2 or CP2 or P2-NPs over 3 days post infection. Infected mice were checked twice daily in the morning at 9 am (early check) and in evening at 7 pm (late check) for clinical symptoms. Unloaded NPs and the isogenic PLY mutant strain (T4Δply) served as negative controls. * denotes P < 0.05 and ** denotes P < 0.005 by Mantel Cox test. Exact P values are shown in Appendix Table S4.",
    "ncbi_link": "PLY: 
ply: "
  },
  {
    "caption": "(E) shRNA-mediated knockdown of USP1 in Hela cells. Soluble extracts were analyzed by immunoblotting.",
    "ncbi_link": "USP1: 7398"
  },
  {
    "caption": "(F) USP1 deubiquitinates Akt during fasting in vivo. Left: Soluble fractions of TA muscles transfected with shLacz control or shUSP1 from fed and fasted mice were analyzed by SDS-PAGE and immunoblotting using anti-Akt. The actin blot serves as a loading control. Right: densitometric measurements of presented blots (n=3). Data is presented as ratio of ubiquitinated Akt to total Akt normalized to actin. * p<0.05 vs. fed by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
USP1: 230484"
  },
  {
    "caption": "(G) USP1 removes K63-linked polyubiquitin chains on Akt in vivo. Akt was immunoprecipitated from the soluble fraction of muscles expressing USP1(C90S) or control plasmids. Mouse IgG was used as a control for non-specific binding. Protein precipitates were subjected to immunoblotting with an antibody against K63-linked polyubiquitin conjugates.",
    "ncbi_link": "USP1: 7398"
  },
  {
    "caption": "(H) USP1 removes polyubiquitin chains linked to K8 on Akt. Akt was immunoprecipitated from the soluble fraction of TA muscles transfected with USP1(C90S) , HA-Akt(K8R) or control from fasted mice, and protein precipitates were analyzed by immunoblotting with anti-Akt antibody. Mouse IgG was used as a control for non-specific binding. Right: Densitometric measurements of presented blots. Data is presented as the ratio between ubiquitinated Akt to total Akt in each lane (n=2).",
    "ncbi_link": "HA: 
Akt: 208///10000///207
USP1: 7398"
  },
  {
    "caption": "(A) Inhibition of USP1 increases PI3K-Akt-FoxO signaling during fasting. Soluble fractions of normal and atrophying muscles expressing shLacz or USP1(C90S) were analyzed by SDS-PAGE and immunoblot. The black line indicate the removal of intervening lanes for presentation purposes. Right: densitometric measurements of presented pAkt (T308), pAkt (S473), and Akt blots. Data is presented as ratio of phosphorylated Akt to total Akt (n=3). * p<0.05 vs. fed by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
USP1: 7398"
  },
  {
    "caption": "(B) Downregulation of USP1 reduces MuRF1 and Atrogin1 expression during fasting. Quantitative RT-PCR of mRNA preparations from atrophying and control muscles expressing shLacz or shUSP1 (80% transfection efficiency) using primers for MuRF1 and Atrogin1. Data are plotted as the mean fold change relative to fed control. n = 4. *, P < 0.05 vs. shLacz in fed. #, P < 0.05 vs. shLacz in fasting by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
Atrogin1: 67731
MuRF1: 433766
USP1: 230484"
  },
  {
    "caption": "(C( Downregulation of USP1 markedly reduces muscle fiber atrophy. Cross-sectional areas of 500 fibers transfected with shUSP1 (that express GFP, green bars) vs. 500 nontransfected fibers (black bars) in the same muscle. n = 5 mice. A representative image is shown; Laminin staining is in red; Bar, 50μm.",
    "ncbi_link": "GFP: 
USP1: 230484"
  },
  {
    "caption": "(D) Downregulation of USP1attenuates the loss of muscle mass during fasting. shUSP1 was delivered to more than 60% of muscle fibers. Mean weights of electroporated muscles are plotted as the percent weight loss. n = 6. #, P < 0.05 vs. shLacz in fed; *, P < 0.05 vs. shLacz in fasting by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
USP1: 230484"
  },
  {
    "caption": "(A) During fasting, downregulation of PHLPP1 enhances Akt phosphorylation at S473. Soluble fractions of muscles transfected with shLacz or shPHLPP1 from fasted mice (2d) were analyzed by immunoblotting. Right: densitometric measurements of presented blots. Data is presented as ratio of shPHLPP1 to shLacz (n=3 for shLacz and n=4 for shPHLPP1). * p<0.05 vs. shLacz in fasting by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
PHLPP1: 98432"
  },
  {
    "caption": "(B) PHLPP1 downregulation increases rates of protein synthesis during fasting. Mice were injected with puromycin, and soluble fractions of electroporated muscles were analyzed by immunoblotting using puromycin antibody. Analysis of right (R) and left (L) limbs for each mouse is shown.",
    "ncbi_link": "PHLPP1: 98432"
  },
  {
    "caption": "(C) Downregulation of PHLPP1 markedly reduces muscle fiber atrophy. Cross-sectional areas of 500 fibers transfected with shPHLPP1 (that express GFP, green bars) vs. 500 nontransfected fibers (black bars) in the same muscle. n = 4 mice. A representative image is shown; Laminin staining is in red; Bar, 50μm.",
    "ncbi_link": "GFP: 
PHLPP1: 98432"
  },
  {
    "caption": "(D) During fasting, Akt is recruited to USP1-PHLPP1-TSC1 complex. TSC1 was immunoprecipitated from the soluble fraction of muscles expressing shLacz or USP1(C90S) from fed or fasted mice. Mouse IgG was used as a control for non-specific binding. Precipitates were analyzed by immunoblotting. Black lines indicate the removal of intervening lanes for presentation purposes.",
    "ncbi_link": "Lacz: 
USP1: 7398"
  },
  {
    "caption": "(E) During fasting, inhibition of USP1 reduces rates of protein synthesis. Mice were injected with puromycin, and soluble fractions of electroporated muscles were analyzed by immunoblotting using puromycin antibody. Right: Densitometric measurement of the presented blot. n = 3. *, P < 0.05 vs. shLacz by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
USP1: 7398"
  },
  {
    "caption": "(F) Inhibition of USP1 results in TSC1 accumulation. Soluble fraction of muscles expressing shLacz or USP1(C90S) from fasted mice were analyzed by SDS-PAGE and immunoblotting. Right: Densitometric measurement of the presented blot. n = 3. *, P < 0.05 vs. shLacz. Data is presented as protein content (AU) in USP1(C90S) vs. shLacz by one-tailed t-test. Data are represented as mean ±SEM.",
    "ncbi_link": "Lacz: 
USP1: 7398"
  },
  {
    "caption": "(G) mTOR inhibition with rapamycin results in reduced USP1 protein content and enhanced Akt phosphorylation at T308. However, a simultaneous downregulation of USP1 is required to promote TSC1 accumulation. Soluble fraction of muscles expressing shLacz or gUSP1 (in vivo CRISPR) from fed and fasted mice injected i.p. with rapamycin (6mg/kg body weight) or saline were analyzed by SDS-PAGE and immunoblot.",
    "ncbi_link": "CRISPR: 
Lacz: 
USP1: 7398
USP1: 230484"
  },
  {
    "caption": "(A) During fasting, inhibition of Dab2-Akt association reduces the interaction of Akt with USP1-PHLPP1-TSC1 complex. Left: TSC1 was immunoprecipitated from the soluble fraction of muscles expressing shLacz or Dab2-DN from fed or fasted mice. Mouse IgG was used as a control for non-specific binding. Precipitates were analyzed by immunoblotting. Right: densitometric measurement of PHLPP1 and TSC1 blots, and data is presented as PHLPP1/TSC1 ratio.",
    "ncbi_link": "Lacz: 
Dab2: 1601"
  },
  {
    "caption": "(B) Dab2 promotes Akt deubiquitination in vivo. Left: Akt was immunoprecipitated from the soluble fraction of muscles expressing shLacz or Dab2-DN from fed and fasted mice using a specific antibody. Mouse IgG was used as a control for non-specific binding. Protein precipitates were analyzed by Western blot analysis using Akt antibody. Right: Densitometric measurements of presented blots. Data is presented as the ratio between ubiquitinated Akt to total Akt in each lane (n=2).",
    "ncbi_link": "Lacz: 
Dab2: 1601"
  },
  {
    "caption": "(C( Dab2 promotes cleavage of K63-linked polyubiquitin chains on Akt in vivo. Akt was immunoprecipitated from the soluble fraction of muscles expressing shLacz or Dab2-DN from fed and fasted mice using a specific antibody. Mouse IgG was used as a control for non-specific binding. Protein precipitates were subjected to immunoblotting with an antibody against K63-linked polyubiquitin conjugates.",
    "ncbi_link": "Lacz: 
Dab2: 1601"
  },
  {
    "caption": "(D) Inhibition of Dab2-Akt association enhances Akt phosphorylation in fasting. Soluble fraction of TA muscles transfected with shLacz or Dab2-DN from fed and fasted mice were analyzed by SDS-PAGE and immunoblotting using the indicated antibodies. Right: densitometric measurement of presented blots. Data are mean ±SEM, n=3. * p<0.05. vs. shLacz in fed conditions, by one-tailed t-test.",
    "ncbi_link": "Lacz: 
Dab2: 1601"
  },
  {
    "caption": "B- Western blot verifying the expression of the CTD variants RPB1-52R and RPB1-25R in U2OS cells in whole cell extracts. U1 snRNP was used as a loading control.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "C- Changes in RNA synthesis upon CTD shortening. MA plot showing RNA synthesis changes in TT-seq datasets upon CTD shortening in U2OS cells in steady state conditions. RPB1-52R cells are used as a control and the data was normalized using spike-in counts. 16214 expressed genes annotated in RefSeq were analyzed. Differentially expressed genes are in red. 473 genes were significantly upregulated (adjusted p value < 0.05, log2 fold change >=1) and 704 genes were significantly downregulated (adjusted p value < 0.05, log2 fold change ≤1).",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "D- Box plot of estimated RNA synthesis rates of expressed RefSeq transcripts (12014 transcripts) based on TT-seq and RNA-seq datasets in RPB1-52R and RPB1-25R cells. Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "E- Box plot of estimated RNA degradation rates of expressed RefSeq transcripts (12014 transcripts) based on TT-seq and RNA-seq datasets in RPB1-52R and RPB1-25R cells. Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "F- Box plot of estimated RNA half-lives of expressed RefSeq transcripts (12014 transcripts) based on TT-seq and RNA-seq datasets in RPB1-52R and RPB1-25R cells. Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "A- Box plots showing ratios of spliced TT-seq reads over total unspliced and spliced TT-seq reads for all constitutive 5'SSs and 3'SSs detected in major RNA isoforms in RPB1-52R and RPB1-25R cells. p value was calculated using Mann-Whitney U test. Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed. B-D- Box plots showing ratios of spliced TT-seq reads over total unspliced and spliced TT-seq reads in RPB1-52R and RPB1-25R cells for all constitutive 5'SSs and 3'SSs detected in major RNA isoforms based on intron position in the transcript: (B) first intron junction, (C) intermediate intron junctions and (D) last intron junctions. p values were calculated using Mann-Whitney U test. Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. ",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "E- Differential mRNA isoform usage upon CTD shortening. Scatter plot showing read counts for mRNA isoforms detected in the chromatin fraction of RPB1-52R and RPB1-25R cells using long read sequencing. 47416 isoforms were detected, RPB1-52R condition was used as a control. 335 isoforms show differential expression (p value < 0.05, Fischer's exact test).",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "B,C- Pol II pause position remains unchanged upon CTD shortening. Histogram of estimated positions of paused Pol II in RPB1-52R and RPB1-25R cells at genes encoding major isoforms with constitutive first exon longer than 100 bp.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "D- Median coverage plot of TT-seq signal at genes encoding major isoforms in RPB1-52R and RPB1-25R cells. Solid lines represent median signal and shaded area refer to 95% bootstrap confidence intervals. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "E- Box plot showing productive transcription initiation rate in RPB1-52R and RPB1-25R cells for genes encoding major isoforms. p value=0.13 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "F- Box plot showing Pol II pausing duration in RPB1-52R and RPB1-25R cells for genes encoding major isoforms with constitutive first exon longer than 100 bp. p value<2.2e-16 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "I- Median coverage plot of TT-seq signal centered at PAS at genes encoding major isoforms in RPB1-52R and RPB1-25R cells. Solid lines represent median signal and shaded area refer to 95% bootstrap confidence intervals. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "J - Box plot showing length of the poly(A) tail in RPB1-52R and RPB1-25R cells measured using Nanopore sequening data. p value<2.2e-16 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "K- Box plot showing distance from the polyadenylation site (PAS) to the transcription termination site (TTS) in RPB1-52R and RPB1-25R cells for 1958 genes encoding major isoforms. p value= 0.8 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "B- Box plots showing RNA synthesis levels (RPKs) of putative eRNAs annotated using TT-seq data in RPB1-52R and RPB1-25R cells. p value =9.27e-103 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "C- Box plots showing lengths of putative eRNAs annotated using TT-seq data in RPB1-52R and RPB1-25R cells. p value =0.000519 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "D - Histogram showing a distribution of number of putative eRNAs paired to genes in RPB1-52R and RPB1-25R cells.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "A- Changes in RNA synthesis in response to 15 min of TPA treatment. MA plot showing RNA synthesis changes in TT-seq datasets upon 15 min treatment with TPA (200 nM) in RPB1-52R and RPB1-25R cells. DMSO treatment of the respective cell line was used as a control and the data was normalized using library size normalization. 14636 expressed genes annotated in RefSeq were analyzed. Differentially expressed genes are in red (adjusted p value < 0.05, log2 fold change >=1 for upregulated genes and adjusted p value < 0.05, log2 fold change ≤1 for downregulated genes ). B- Box plots showing log2 fold change of genes significantly upregulated upon 15 min treatment with 200 nM TPA in RPB1-52R and RPB1-25R cells (adjusted p value < 0.05, log2 fold change >=1). P value =0.02257 (Mann-Whitney test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed. C- Changes in RNA synthesis in response to 30 min of TPA treatment. MA plot showing RNA synthesis changes in TT-seq datasets upon 30 min treatment with TPA (200 nM) in RPB1-52R and RPB1-25R cells. DMSO treatment of the respective cell line was used as a control and the data was normalized using library size normalization. 14636 expressed genes annotated in RefSeq were analyzed. Differentially expressed genes are in red (adjusted p value < 0.05, log2 fold change >=1 for upregulated genes and adjusted p value < 0.05, log2 fold change ≤1 for downregulated genes) D- Box plots showing log2 fold change in RNA synthesis of genes significantly upregulated upon 30 min treatment with 200 nM TPA in RPB1-52R and RPB1-25R cells (adjusted p value < 0.05, log2 fold chage >=1). P value =0.001749 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed. ",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "A- Histogram showing the distribution of a number of putative eRNAs paired to genes in RPB1-52R and RPB1-25R cells upon 15 and 30 min TPA treatment (200 nM) as well as in the DMSO controls.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "B- Box plots showing RNA synthesis levels (RPK) of putative eRNAs paired with genes upregulated (adjusted p value < 0.05, log2 fold change >=1) in RPB1-52R and RPB1-25R cells upon 15 min of TPA treatment (200 nM). p value = 0.000732 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed. C- Box plots showing RNA synthesis levels (RPK) of putative enhancer eRNAs paired with genes upregulated (adjusted p value < 0.05, log2 fold change >=1) in RPB1-52R and RPB1-25R cells upon 30 min of TPA treatment (200 nM). p value = 2.77e-5 (Mann-Whitney U test) Box limits are the first and third quartiles, the band inside the box is the median. The ends of the whiskers extend the box by 1.5 times the interquartile range. Two independent biological replicates were analyzed. ",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "G. Polysome profiles of stm1∆ cells containing either full-length or N-terminally deleted or C-terminally deleted Stm1 mutants upon nitrogen starvation for 1 hour.",
    "ncbi_link": "stm1: 850843
Stm1: 850843"
  },
  {
    "caption": "H. Binding of full-length or deletion mutants of Stm1 across the polysome profile fractions shown in Figure 2E. 9 equal volume fractions of each polysome profile were precipitated and analyzed by immunoblot for Stm1 and Rpl3. At least two biological replicates are used for each mutant.",
    "ncbi_link": "Stm1: 850843"
  },
  {
    "caption": "C. Polysome profiles of wild-type and stm1∆ cells under nitrogen starvation for 1 hour. D. Polysome profiles of wild-type and STM1AAA cells under nitrogen starvation for 1 hour. E. Polysome profiles of wild-type and STM1EEE cells under nitrogen starvation for 1 hour. F-",
    "ncbi_link": "stm1: 850843
STM1: 850843"
  },
  {
    "caption": "A-B. Ribosomal subunit profiles (A) and quantitation of ribosome content (B) of stm1∆, wild-type, STM1AAA, and STM1EEE cells treated with rapamycin for 24 hours. For the ribosomal subunit profile analyses, the cell extracts were treated with 50 mM EDTA and separated on 5-25% sucrose density gradients. At least five biological replicates are used for calculation of p-values from multiple unpaired t-tests are indicated in the graphs.",
    "ncbi_link": "stm1: 850843
STM1: 850843"
  },
  {
    "caption": "E-G. Immunoblot of Rpl24-GFP and free GFP (E), quantification of total GFP relative to Pgk1 (F), and free GFP relative to Rpl24-GFP (G) in stm1∆, wild-type, STM1AAA, and STM1EEE cells treated with rapamycin for 24 hours. At least six biological replicates are subjected to statistical analysis using multiple unpaired t-tests. (s.e. for short exposure; l.e. for long exposure).",
    "ncbi_link": "stm1: 850843
STM1: 850843"
  },
  {
    "caption": "J-K. Immunoblot (J) and the quantification (K) of Rpl3 in wild-type and stm1∆ cells without rapamycin, or with rapamycin for 24 hours along with or without bortezomib treatment for 8 hours. At least six biological replicates are subjected to statistical analysis using multiple unpaired t-tests.",
    "ncbi_link": "stm1: 850843"
  },
  {
    "caption": "A-B. Puromycin incorporation (A) and its quantification (B) in stm1∆, wild-type, STM1AAA, and STM1EEE cells starved of nitrogen for 24 hours and restimulated with amino acids (+ N) for 10, 20, or 30 minutes. Immunoblots for puromycin, Stm1, Rpl3, and Pgk1 are shown. Relative puromycin incorporation for at least five biological replicates is subjected to multiple unpaired t-tests.",
    "ncbi_link": "stm1: 850843
STM1: 850843"
  },
  {
    "caption": "D-E. Representative fluorescent microscopic images for expression of Rpl24-GFP (D) and its intensity quantification (E) in tetrads of control (RPL24GFP) and stm1∆ RPL24GFP cells (n=100, each). Experiments are performed at least three times. Statistical analysis is done by unpaired t-test.",
    "ncbi_link": "GFP: 
RPL24: 
stm1: 850843"
  },
  {
    "caption": "I-J. Immunoblot for ubiquitin (I) and its quantification (J) in the supernatant and ribosomal pellet obtained from HEK293T cells treated with control sgRNA (sgCtrl) or SERBP1 sgRNA (sgSERBP1) along with INK128 treatment for 48 hours. At least four biological replicates are analyzed by unpaired t-test. Data are presented as the mean ± SD.",
    "ncbi_link": "SERBP1: 26135"
  },
  {
    "caption": "A. SF-1, FATE1 and β-tubulin protein levels shown in basal condition and after Dox treatment in H295R/TR, H295R/TRSF-1, H295R/TRFATE1 and H295R/TR N-FlagFATE1cells.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "B. FATE1 mRNA expression is increased in H295R/TRSF-1 cells by Dox treatment. The efficiency of FATE1 knockdown by specific (siFATE1) vs. control (siC) siRNA nucleofection is shown (mean ± SEM; n=4 with 3 replicates/experiment).",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "C. Immunofluorescence microscopy showing endogenous FATE1 protein (red) induction of expression by Dox-treatment of H295R/TRSF-1 cells. SF-1 (green), DAPI (blue). Scale bars, 10 μm.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "D. Subcellular localization of endogenous FATE1 (red) and transfected fluorescent markers for Golgi, ER and mitochondria, respectively (green) in Dox-treated H295R/TRSF-1 cells. DAPI (blue). Scale bars, 10 μm.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "I. FATE1 and VDAC1 are associated with the pellet (membrane; P) fraction after high-speed centrifugation of the alkaline-extracted mitochondrial fraction of Dox-treated H295R/TR SF-1 cells, while cytochrome c is found in the supernatant (S).",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "B. Subcellular localization of EGFP-fusions of full-length (FL) FATE1 and its mutants: N-terminal (aa. 1-124), C-terminal (aa.125-183), 1-162, transmembrane domain (aa. 155-183) and L151D (green) transfected in H295R/TRSF-1 cells. Mitochondria were stained by anti-TOM20 antibody (red) and DNA by DAPI (blue). Scale bars, 10 μm.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "F. Mitochondrial localization of Mic60/mitofilin (green) and FATE1 (red) in Dox-treated H295R/TRSF-1 cells. Scale bar, 10 μm.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "G. Left, triple immunofluorescence microscopy labelling of endogenous FATE1 (green), ER labelled by calreticulin (red) and mitochondria labelled by HSP60 staining (blue) in Dox-treated H295R/TRSF-1 cells. One area showing close apposition of red, green and blue staining (white signals) is shown at higher magnification. Scale bar, 10 μm. Right, graph showing quantification of FATE1 signal in total mitochondria (white histogram) vs. ER-mitochondria contact sites (red histogram) (mean ± SEM; n=13). **p<0.01.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "H. H295R/TRSF-1 cells were fractioned into crude mitochondria (CM), endoplasmic reticulum (ER), purified mitochondria (PM) and mitochondria-associated membranes (MAM) fractions. H, total homogenate. The localization of SERCA2, SOAT1, VDAC1, GRP75, S1R, EMD, Mic60/mitofilin, FATE1 and TOM20 proteins in the different fractions was revealed by immunoblot.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "A. H295R/TR N-FlagFATE1 cells were transfected with D1 ER marker for ER (green) and mtRFP marker for mitochondria (red). Manders' coefficient for green-red signals colocalization in basal (white histograms) and Dox-treated (black histograms) cells is shown on the right (mean ± SEM; n=12). ***p<0.001. Scale bars, 10 μm.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "B. Effect of FATE1 expression on ER-mitochondria distance in H295R/TR N-FlagFATE1 cells measured using a split-GFP probe [29]. Quantification is shown in the graph. White histogram, number of fluorescent objects/cell in basal conditions; black histogram, number of fluorescent objects/cell in Dox-treated cells (mean ± SEM; n=6 with 90 cells analyzed in total). **p<0.01. Scale bars, 5 μm.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "C. Transmission electron microscopy images of H295R/TR N-FlagFATE1 cells cultured in basal conditions or treated with Dox. ER-mitochondria contacts are indicated by white arrowheads. Scale bars, 200 nm. Right, quantification of the number of contacts normalized by the number of mitochondria and the percentage of mitochondria with ER contact sites is shown in basal conditions (white histograms) and after Dox treatment (black histograms) of cells (mean ± SEM; n=38 for basal and 47 for Dox-treated cells). ***p<0.001.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "D. Transmission electron microscopy images of H295R/TRSF-1 cells cultured in basal conditions or treated with Dox. ER-mitochondria contacts are indicated by white arrowheads. Scale bars, 200 nm. Right, quantification of the number of contacts normalized by the number of mitochondria and the percentage of mitochondria with ER contact sites is shown in basal conditions (white histograms) and after Dox treatment (black histograms) of cells (mean ± SEM; n=41 for basal and 42 for Dox-treated cells). ***p<0.001.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "E. Mitochondrial shape (BacMam Mitochondria-RFP; in red) in H295R/TR N-FlagFATE1 cells shown by fluorescence confocal microscopy in basal conditions and after Dox treatment. FATE1 (green), DAPI (blue). A higher magnification of merged green and red signal is shown in the insets. Scale bars, 10 μm.F. Mitochondrial fragmentation index in H295R/TR N-FlagFATE1 cells after Dox treatment (red histogram) compared to cells cultured in basal conditions (white histogram) (mean ± SEM; n=111 for basal and 101 for Dox-treated cells). ***p<0.001.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "G. Mitochondrial fragmentation index in H295R/TRSF-1 cells after Dox treatment (green histogram) compared to cells cultured in basal conditions (white histogram). (mean ± SEM; n=37 for basal and 49 for Dox-treated cells). ***p<0.001.",
    "ncbi_link": "SF-1: 7536"
  },
  {
    "caption": "H. Mitochondrial membrane potential (∆Ψ) measured by TMRM fluorescence after Dox treatment of H295R/TR N-FlagFATE1 cells (red histogram) compared to cells cultured in basal conditions (white histogram). Mean ± SEM is shown. (mean ± SEM; n=3 with 12 replicates/experiment). ns, not significant.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "A. MitochondrialCa2+ uptake. H295R/TR parental clone (white/grey histograms) H295R/TRSF-1 (white/green histograms), H295R/TR N-FlagFATE1 (white/red histograms) and H295R/TRFATE1 cells (white/violet histograms) (mean ± SEM; n=3-5 with 12 replicates/condition). **p<0.01; ***p<0.001; ns, not significant.B. CytosolicCa2+ concentration. Histograms as in A (mean ± SEM; n=3-5 with 12 replicates/condition). ns, not significant.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "C. Mitochondrial (left) and cytosolic (right) Ca2+ concentrations in Dox-treated H295R/TRSF-1 cells transfected with control (siC; white histograms) or FATE1-specific (siFATE1; green histograms) siRNAs (mean ± SEM; n=3-5 with 12 replicates/condition). ***p<0.001; ns, not significant.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "D. Caspase 3/7 activity in H295R/TR N-FlagFATE1 cells cultured in basal conditions (white histograms) or in the presence of Dox (red histograms) treated with H2O2 (500 μM) C2-ceramide (50 μM) or staurosporine (STS) (1 μM). (mean ± SEM; n=5-8 with 3 replicates/condition). *p<0.05; **p<0.01; ns, not significant.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "E. Caspase 3/7 activity in Dox-treated H295R/TRSF-1 cells transfected with control (siC; white histograms) or FATE1-specific (siFATE1; green histograms) siRNAs and treated with H2O2 or STS (mean ± SEM; n=5-8 with 3 replicates/condition). *p<0.05; ns, not significant.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "F. Flow cytometry analysis of TUNEL staining in H295R/TR N-Flag FATE1 cells cultured in basal conditions or in the presence of Dox treated with vehicle (control) H2O2 (500 μM), C2-ceramide (50 μM) or staurosporine (STS) (1 μM).",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "G. Caspase 3/7 activity in H295R/TR N-FlagFATE1 cells cultured in basal conditions (white histograms) or in the presence of Dox (red histograms) and treated with mitotane (50 μM) (mean ± SEM; n=5-8 with 3 replicates/condition). **p<0.01.",
    "ncbi_link": "FATE1: 89885"
  },
  {
    "caption": "H. Caspase 3/7 activity in Dox-treated H295R/TRSF-1 cells transfected with control (siC; white histograms) or FATE1-specific (siFATE1; green histograms) siRNAs and treated with mitotane (mean ± SEM; n=5-8 with 3 replicates/condition). *p<0.05.",
    "ncbi_link": "FATE1: 89885
SF-1: 7536"
  },
  {
    "caption": "(A) Frequency of CHD1 gene mutation (green) deep deletion (blue) or amplification (red) in prostate cancer patients.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(B) CHD1 is recruited to an I-SceI-induced DSB site and is co-localized with γH2AX. Immunofluorescence studies using U2OS19 ptight13 GFP-LacR cells containing a stably integrated I-SceI cleavage site flanked by 256 copies of lac operator (lacO) on one side and 96 copies of the tetracycline response element on the other side (tetO). The localization of the GFP-lac repressor protein (GFP-LacR) at the lac-operator DNA sequences in the nucleus before (− I-SceI) and 16 h after I-SceI-induced (+ I-SceI) DSB. After 16 h of doxy treatment, CHD1 and γH2AX co-localized at I-SceI cleavage site, along with DNA-bound GFP-LacR but not in uninduced cells (−I-SceI). Scale bar 10 µm.",
    "ncbi_link": "lacO: 
tetO: 
I-SceI: 854590"
  },
  {
    "caption": "(F) CHD1 is recruited to the chromatin upon DNA double strand break induction. PC3 cells with stable control (shCont) or CHD1 shRNA (shCHD1) expression were treated with NCS for the indicated time points and chromatin fractions were immunoblotted with CHD1 and γH2AX antibodies. H2B was used as a loading control. See also Figure EV1A-EV1F.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(A, B) BHP1 or PC3 cells with stable expression of either control (shCont) or CHD1 shRNA (shCHD1) were treated with γ-radiation (3 Gy) and after 1 h and 24 h cells were immunostained for γH2AX (A) and the number of γH2AX foci per cell were determined for each time point, more than 50 cells were counted in each condition (B). Scale bar 5 µm. The mean values of three independent experiments (± SD) are shown. p-values (0.0008 and 0.006, **p ≤ 0.01, ***p ≤ 0.001) were calculated using ANOVA.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(C) CHD1 depleted cells show prolonged γH2AX accumulation. PC3 cells with shCont or shCHD1 were treated with γ-radiation as in (A) and total protein was analyzed by Western blot.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(D) CHD1-depleted cells show increased sensitivity to γ-radiation. For colony formation assay, both BHP1 and PC3 cells with shCont or shCHD1 were treated with the indicated doses of γ-radiation and surviving fractions were measured by counting colonies after 3 weeks, mean values are represented in the plot (n=3, ± SD). Data were normalized to the plating efficiency. p-values (0.0009 and 0.002, **p ≤ 0.01, ***p ≤ 0.001) were calculated using ANOVA. See also Figure EV2A-EV2B.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(A, B) HeLa cells harboring single copies of HR (pGC) or NHEJ (pEJ) repair substrates were transfected with either negative control (siCont) or siRNAs targeting CHD1, RAD51 or XRCC4. After 24 h of transfection, DSB was induced by transfecting cells with I-Sce-I-expressing vector (pCMV-I-SceI-3xNLS). After 48 h of transfection, GFP-positive cells were measured by flow cytometry. HR (A) or NHEJ (B) efficiency was calculated based on the fraction of GFP-positive cells and represented as mean values from three independent experiments as ± SD, 50,000 cells were counted for each condition.",
    "ncbi_link": "CHD1: 1105
RAD51: 5888
XRCC4: 7518"
  },
  {
    "caption": "(C) CHD1-depleted cells show decreased RAD51 foci after DNA damage induction. The shCont or shCHD1 PC3 cells were irradiated and co-immunostained with γH2AX and RAD51 antibodies after the indicated time points. Scale bar 5 µm. (D) The number of RAD51 foci co-localized with γH2AX per cell (from C) were counted (n=50) and represented in a graph. The data is represented in mean value of three independent experiments as ± SD, more than 50 cells were counted for each condition. See also Figure EV3A-EV3F.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(B) shCont and shCHD1 PC3 cells were treated with NCS for the indicated times and chromatin fractions were immunoblotted for CtIP, RPA1 and RAD51. H2B is shown as a loading control.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "CHD1 depletion leads to decreased (C) CtIP and (D) RPA1 recruitment to I-SceI-induced DSB in U2OS19 ptight13 GFP-LacR cells. CHD1 was depleted in U2OS19 ptight13 GFP-LacR cells by siRNA and 48 h after transfection cells were treated with doxy for 16 h and co-immunostained for γH2AX and CtIP or RPA1. The number of cells with CtIP or RPA1 foci from (C) and (D) were counted and represented the mean in the graph as percentage of foci positive cells as ± SD (n=3), more than 50 cells were counted. Scale bar 5 µm.",
    "ncbi_link": "CHD1: 1105
I-SceI: 854590"
  },
  {
    "caption": "(E) PC3 cells were transfected either with mock or siCHD1 followed by empty vector, wt mChd1 (Wt) or ATPase-mutant (Mt) mChd1. After 48 h of transfection cells were treated with of 4-OH tamoxifen (4-OHT) for 24 h and processed for PLA with γH2AX and CtIP antibodies. Cells demonstrating positive focal interactions indicative of DNA repair hubs (punctate staining) are present only in control and (Wt) CHD1-rescued cells but not following knockdown or reconstitution of an ATPase-mutated CHD1 (Mt). Scale bar 20 µm.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(F) PC3 cells which stably express HA-mChd1-ERT2, were transfected with either mock or siCHD1. After 24 h of transfection cells were treated with 4-OHT for 24 h to induce HA-mChd1-ERT2 nuclear translocation. Western blot analysis of chromatin fractions for CHD1, ERT2 (mChd1), CtIP and RAD51 shown in Figure EV4O were analyzed by densitometry using ImageJ. The relative quantification for the indicated proteins is shown in the graph. See also Figure EV4A-EV4P.",
    "ncbi_link": "Chd1: 1105
CHD1: 1105
ERT2: 2100"
  },
  {
    "caption": "(A) CHD1 recruitment is dependent on MRE11 activity. PC3 cells were transfected with mock or siMRE11 (SmartPool) and 48 h after transfection cells were treated with NCS and chromatin fractions were isolated and analyzed by Western blot.",
    "ncbi_link": "MRE11: 4361"
  },
  {
    "caption": "(B) CHD1 is upstream of CtIP. PLA with γH2AX and CHD1 antibodies in mock or CtIP depleted cells after 2 h of NCS. Scale bar is 50 µm. Verification of knockdown efficiency is shown by Western blot on the right. HSC70 is shown as a loading control. Scale bar 20 µm. (C) Quantification of PLA signal from (B) represented as mean values from three independent experiments as ± SD, more than 100 cells were counted per condition.",
    "ncbi_link": "CtIP: 5932"
  },
  {
    "caption": "(D) qPCR analyses for chromatin accessibility at two HR-repaired sites (DSB-I and DSB-II) was analyzed by FAIRE in AsiSI-ER-U20S cells transfected with either mock or CHD1 siRNA. After 48 h of transfection cells were treated with 4-OHT for the indicated time points and processed for FAIRE. The data are represented as mean ± SD (n=3) p-values were calculated using ANOVA (0.02 and 0.03, *p ≤ 0.1).",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(E) Native BrdU staining of PC3 cells transfected either with mock or siCHD1 (SmartPool) were grown for 48 h and then treated with NCS for 2 h prior to staining with anti-BrdU and γH2AX antibodies. Scale bar 5 µm.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(A) CHD1-depleted cells show hypersensitivity to Mitomycin (MMC) treatment. For colony formation assay shCont and shCHD1 PC3 cells were treated with the indicated MMC concentrations for 4 h and surviving fractions were measured by counting colonies after 3 weeks and mean values were represented (n=3, ± SD, p-value=0.0002, ANOVA, ***p ≤ 0.001).",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(B) CHD1-depleted cells show increased hypersensitivity to Irinotecan. For cell proliferation analysis, shCont and shCHD1 cells were treated with 1 µM Irinotecan and proliferation was measured by Celigo and the relative confluency (mean) was plotted in the graph (n=3, ± SD, p-value=0.0004, ANOVA, ***p ≤ 0.001).",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(C) Loss of CHD1 leads to increased sensitivity to PARP inhibition. Control or CHD1-depleted BPH1 cells were treated with the indicated concentrations of the PARP inhibitor olaparib and surviving fractions were measured by counting colonies after 3 weeks. Data represented as mean values (n=3, ± SD, p-value=0.0003, ANOVA, ***p ≤ 0.001).",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(D) CHD1 depletion render cells sensitive to PARP inhibition in combination with irradiation. shCont- or shCHD1-expressing BHP1 cells were treated with 1 µM of PARP inhibitor olaparib for 2 h before irradiation with indicated doses of X-rays and surviving fractions (normalized to the unirradiated condition) were measured by counting colonies after 3 weeks. Data is represented as mean ± SD (n=3, p-value=0.07, ANOVA, *p ≤ 0.1).",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "(E) Frequency of CHD1 gene alterations in comparison with DSB repair genes in prostate cancer patients. Data obtained from cBioPortal for Cancer Genomics. (F) Frequency of CHD1 gene alterations from indicated data sets. See also Figure EV5A-EV5B.",
    "ncbi_link": "CHD1: 1105"
  },
  {
    "caption": "C. Overexpression analysis of Mcm2-7ΔC2 shows that this mutant causes dominant lethality, indicating that the C-terminus of Mcm2 is essential in cell survival.",
    "ncbi_link": "Mcm2: 852258"
  },
  {
    "caption": " (A) Temperature-dependent poison events in Hnrnpdl (left, see also Figure 1C), Hnrnph3 (middle) and Cirbp (right). For each target, on top a simplified exon-intron structure is given and below Sashimi plots show the distribution of raw sequencing reads. Exon-Exon junction reads are indicated by the numbers connecting the exons. Below, sequence conservation across placental species is indicated. Hnrnpdl exhibits a heat-included exon that leads to a PTC, Hnrnph3 a cold-skipped exon that leads to a frameshift, and in Cirbp, heat leads to inclusion of an alternative transcript end, which leads to formation of a PTC. (B) For each gene from A, the triplicate normalized read counts in DMSO (left y-axis, green) and the percentage of the poison isoform in CHX (right y-axis, orange) are plotted at the two temperatures. Line represents mean PSI. ",
    "ncbi_link": "Cirbp: 12696
Hnrnpdl: 50926
Hnrnph3: 432467"
  },
  {
    "caption": " (E) Splicing reporters, containing only an intron (GFP ctrl, #1) or additionally temperature-dependent exons with ~1kB surrounding introns. Representative radioactive RT-PCRs (bottom) confirm cold-induced inclusion of Ythdf3 exon 7 (#2) and human Synerg exon 21 (#3) after 24 hours at the indicated temperatures. Representative images are derived from three independent gels. See SourceDataForFigure2E for uncropped versions of these gels. ",
    "ncbi_link": "GFP: 
Synerg: 
Ythdf3: 229096"
  },
  {
    "caption": " (F-G) GFP expression was quantified using FACS and is shown relative to GFP ctrl. In (F) transfected cells were incubated at the indicated temperatures for 24 hours (n=3, mean +/- SD). In (G) cells were incubated directly after transfection for 12 hours at 39°C (blue) or 33°C (red) and then shifted for 2, 4, 8 and 12 hours (n=3, mean +/- SD). ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " (A) SR protein specific temperature-dependent AS-decay. Sashimi plots are shown for heat-induced poison exon inclusion for Srsf2 (left) and cold-induced poison isoform formation for Srsf10 (right). Quantification of GE and AS are presented in the center (as in Figure 2B), lines represent mean. ",
    "ncbi_link": "Srsf10: 10772
Srsf2: 6427"
  },
  {
    "caption": " (B) Poison exon inclusion for Srsf2 (left) and Srsf10 (right) in a 24h temperature-rhythm in human cells. Hek293 cells were pre-entrained with square-wave temperature cycles (12h 34°C/ 12h 38°C) for 48h. For the last 24h, cells were treated with DMSO or CHX every 4h and harvested after 4h and analyzed by splicing sensitive RT-PCR (n=3, mean ± SD). White area: 34°C; Red area: 38°C. In Hek293 cells, inclusion of Srsf10 exon 3 is coupled to polyadenylation making it a weak decay target. ",
    "ncbi_link": "Srsf10: 10772
Srsf2: 6427"
  },
  {
    "caption": " (E) Quantification of Srsf2 AS-decay in hamster, rabbit and chicken cells (n=2, mean ± SD). Statistical significance was determined by 2-way ANOVA, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Box plots show median PSI of validation PCRs, whiskers show min to max. Individual data points are shown as circles. ",
    "ncbi_link": "Srsf2: 6427"
  },
  {
    "caption": " Rhythmic Srsf2 productive mRNA levels (relative to Gapdh) were analyzed by RT-qPCR. For each clone, expression is normalized to time point 52h, ",
    "ncbi_link": "Gapdh: 2597
Srsf2: 6427"
  },
  {
    "caption": " Rhythmic Srsf10 productive mRNA levels (relative to Gapdh) were analyzed by RT-qPCR. For each clone, expression is normalized to time point 52h For Srsf10 two independently generated clones were investigated (∆E3 A and B). Statistical significance was determined by unpaired t-test and is indicated by asterisks: p values: **p<0.01, ****p<0.0001. ",
    "ncbi_link": "Gapdh: 2597
Srsf10: 10772"
  },
  {
    "caption": " Comparing temperature-induced expression of the core clock components Bmal1 in WT and Srsf10 ∆E3 cells (relative to Gapdh, normalized to time point 52h). Statistical significance was determined by unpaired t-test and is indicated by asterisks: p values: *p<0.05, ***p<0.001, ****p<0.0001. n=3, mean ± SEM. ",
    "ncbi_link": "Bmal1: 406
Gapdh: 2597
Srsf10: 10772"
  },
  {
    "caption": " Comparing temperature-induced expression of the core clock components Per1 in WT and Srsf10 ∆E3 cells (relative to Gapdh, normalized to time point 52h). Statistical significance was determined by unpaired t-test and is indicated by asterisks: p values: *p<0.05, ***p<0.001, ****p<0.0001. n=3, mean ± SEM. ",
    "ncbi_link": "Gapdh: 2597
Per1: 5187
Srsf10: 10772"
  },
  {
    "caption": " (C) Sashimi plots as shown in Figure 2A (without conservation score) for decay-inducing AS events upon cold (At-SCL33, left) or warm temperature (At-SR34, right). Data shown represent, from top to bottom, warm-dark, warm-light, cold-dark and cold-light conditions as indicated on the right of the plots. (D) For validation, A. thaliana were incubated for 3 days either at 20°C or 4°C and RNA was investigated for gene expression (green, left y-axis) and poison isoform formation (orange, right y-axis). Gene expression of At-SCL33 (left) or At-SR34 (right) is shown relative to Ipp2. Lines represent mean, individual data points are shown. ",
    "ncbi_link": "Ipp2: 820960
SCL33: 841976
SR34: 839262"
  },
  {
    "caption": " (B) Correlation of rhythmic Srsf10 expression (orange, left y-axis) and exon 3 inclusion (black, right y-axis) in mouse liver samples from the indicated ZTs (n=4, mean +/- SEM). Quantifications were obtained by RNA-seq analysis of datasets from (Atger et al., 2015). ",
    "ncbi_link": "Srsf10: 14105"
  },
  {
    "caption": "B Relative (left) and absolute (right) amount of 13C-Lys-labeled and unlabeled Aβ  in APPtg mouse brains  after labeling from 75-125 d (n = 1), 75-175 d (n = 4), 50-100 d (n = 5), 50-125 d (n = 2), 50-150 (n = 4) or 50-175 d (n = 9) of age. Error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "C Representative chromatogram  and mass spectra of doubly charged ions of unlabeled Aβ17-28 (663.3 m/z) and 13C-Lys Aβ17-28 (666.3 m/z) in an  APPtg brain  after labeling from 75-175 d. %- ion intensity, m/z- mass-to-charge. Data were acquired in data-independent analysis mode (MSE). D Representative chromatograms  of unlabeled  Aβ17-28  (left) and 13C-Lys Aβ17-28 (right) in an APPtg brain  after labeling from 50-175 d. The intensities of 4 transitions (y10, y9, y8, and y7) were assessed. Data were acquired by MRM  in nanoflow mode.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "F Representative chromatograms  of unlabeled Aβ17-28  (left) and 13C-Lys Aβ17-28 (right) in a non-APPtg brain  after labeling  from 90-100 d. Data were acquired by MRM  in microflow mode.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "D Decreasing quantities of synthetic 13C15N-Lys Aβ1-42 were spiked into the insoluble fraction of APPtg brains, immunoprecipitated, trypsin-digested, and analyzed by MRM. Assessment of the intensities of y10, y9, y8 and y7 showed a detection limit level of 50 amol for 13C15N-Lys Aβ17-28 and detected an excess of brain-derived unlabeled Aβ17-28. Measurements in technical triplicates, normalization to total ion current. Error bars show mean ± SD",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "B Temporal MRM  analysis of 13C-Lys Aβ17-28 and unlabeled Aβ17-28 in the liver, spleen, mesenteric lymph nodes, and peritoneal cells after 13C-Lys-APPtg brain  extract i.p. injection (n = 3 mice per  time point  and tissue at 1-10 d, except for n = 2 mice  for  peritoneal cells at 3 d; n = 4 mice per time point and tissue at 25-100 d, except for n = 3 mice  for spleen  at 100 d). Measurements in technical triplicates, normalization to  13C15N-Lys Aβ17-28  intensity as a spiked internal standard and additionally to organ weight  (mg) for  lymph nodes. Error bars show median ± interquartile range.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "C Temporal 4G8 immunoassay  quantification of Aβ42  in the liver, spleen,  mesenteric lymph nodes, and peritoneal cells after unlabeled APPtg (n = 8 mice  at 5 h - 7 d, except for n = 5 mice  for  peritoneal lavage, n = 5 mice  at 10-14 d, n = 4 mice  at 21 d) or non-tg brain  extract injection (n = 2 mice  at 5 h and 3 d, n = 3 mice  at 1 d, n = 1 mouse  at 5 and 7 d, except for peritoneal cells where n = 1 mouse  at 5 h and 3 d, and n = 2 mice  at 1 d). Error bars show median ± interquartile range. D Normalization of APPtg extract group data presented in (C) to organ weight  (mg) and injected  Aβ amount (range 1,027-1,426 ng). Error bars show median ± interquartile range.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "A Temporal MRM  analysis of unlabeled Aβ17-28 and 13C-Lys Aβ17-28 in the soluble brain  fraction after 13C-Lys APPtg brain  extract i.p. injection (n = 3 mice  per  time point  at 1-10 d, n = 4 mice per time point  at 25-100 d). Data information: measurements in technical triplicates, normalization to 13C15N-Lys Aβ17-28 intensity as a spiked internal standard and brain weight  (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Comparative MRM  analysis of 13C-Lys Aβ17-28 (B) in the insoluble brain  fraction after 13C-Lys-APPtg brain  extract (donors labeled  for 50-125 d) and 13C-Lys-non-tg brain  extract (donors labeled  for 10 d) i.p. injection (n = 3 mice  per group and time point at 1-10 d, n = 4 mice  per group and time point at 25, 50, 100 d, n = 3 mice  in the APPtg extract group and n = 4 in the non-tg extract group at 75 d), right side zoom for time points  1-10 d. Unpaired two-tailed t-test * p<0.05 (P=0.0129 at 3 d, P=0.0156 at 10 d, P=0.0109 at 25 d), ** p<0.01 (P=0.0091 at 1 d, P=0.0011 at 5 d), *** p<0.001 (P=0.0006 at 7 d), 13C-Lys APPtg extract-injected vs 13C-Lys  non-tg extract-injected for each  time point. Data information: measurements in technical triplicates, normalization to 13C15N-Lys Aβ17-28 intensity as a spiked internal standard and brain weight (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "C Comparative MRM analysis of unlabeled Aβ17-28 (C) in the insoluble brain  fraction after  13C-Lys-APPtg brain extract (donors labeled  for 50-125 d) and  13C-Lys-non-tg brain  extract (donors labeled  for 10 d) i.p. injection (n = 3 mice  per group and  time point at 1-10 d, n = 4 mice  per group and  time point  at 25, 50, 100 d, n = 3 mice  in the APPtg extract group and n = 4 in the non-tg extract group at 75 d), right side zoom for  time points 1-10 d. Unpaired two-tailed t-test * p<0.05 (P=0.0129 at 3 d, P=0.0156 at 10 d, P=0.0109 at 25 d), ** p<0.01 (P=0.0091 at 1 d, P=0.0011 at 5 d), *** p<0.001 (P=0.0006 at 7 d), 13C-Lys APPtg extract-injected vs 13C-Lys  non-tg extract-injected for each  time point. Data information: measurements in technical triplicates, normalization to 13C15N-Lys Aβ17-28 intensity as a spiked internal standard and brain weight  (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "D Comparative 4G8 immunoassay   quantification of Aβ42  in the insoluble brain  fraction after  13C-Lys APPtg or  13C-Lys  non-tg brain  extract i.p. injection (n = 3 mice  per group and  time point at 1-10 d, n = 4 mice  per group and time point  at 25-100 d), right side zoom for time points 1-10 d. Normalization to protein concentration.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "E Representative chromatograms  of unlabeled Aβ17-28 (left) and 13C-Lys Aβ17-28 (right) in the brain  of an unlabeled 50-day-old APPtg mouse  not injected with labeled brain  extract. Note the absence of 13C-Lys Aβ17-28.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "F MRM  analysis of unlabeled and 13C-Lys-labeled Aβ17-28 in  APPtg mouse brains  after 13C-Lys-labeled  diet for 1 or 3 d (n = 3 mice  per time point). Data information: measurements in technical triplicates, normalization to 13C15N-Lys Aβ17-28  intensity as a spiked internal standard and brain weight  (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "G  Comparative MRM analysis  of  13C-Lys Aβ17-28  in the insoluble brain  fraction after 13C-Lys APPtg and 13C-Lys  non-tg brain  extract (all donors labeled  for 100 d) i.p. injection (n = 6 mice  per group). Data information: measurements in technical triplicates, normalization to  13C15N-Lys Aβ17-28  intensity as a spiked internal standard and brain weight  (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "H MRM  analysis of unlabeled and  13C-Lys-labeled Aβ17-28 in non-APPtg mouse brains  after 13C-Lys-labeled diet for 1 d (n = 3 mice) or at 1 d after 13C-Lys-APPtg brain  extract i.p. injection (n = 3 mice). Data information: measurements in technical triplicates, normalization to 13C15N-Lys Aβ17-28 intensity as a spiked internal standard and brain weight  (mg). All error bars show mean ± SD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Expression data (RNAseq) for significantly differentially expressed genes (q-value < 0.05, FDR-adjusted p-value, n=2 biological replicates for each condition). Scatter plot shows log2(fold change) of gene expression data comparing endpoint to initial populations for Exp. 1 and Exp. 2 (grey dots) with the location of the gene in the reference genome as the x-axis. Those genes that are associated with AraC transcription units are highlighted (red dots for Exp. 1 and blue dots for Exp. 2). Above the plot, the transcription units are labeled green if AraC activates expression (in the presence of arabinose) or red if AraC represses expression of those genes.",
    "ncbi_link": "AraC: 944780"
  },
  {
    "caption": "Growth rate analysis of various weaned (starting point of static phase) and optimized (endpoint of static phase) strains with or without fucK or araB genes knocked out. Strains were grown in triplicate (n=3) on M9 minimal media with D-arabinose as the sole carbon source. The colored bars represent the calculated mean growth rate and the error bars represent the standard deviation. The p-values reported were calculated using a two-sided Welch's t-test.",
    "ncbi_link": "araB: 946017
fucK: 946022"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative TCRβ+ T cell content in colon (n=10) and tumor (n=22). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Anti-CD3 immunostaining on normal colon (left panel) and a representative colon tumor section derived from an Apcfl/fl-Cdx2CreERT2 mouse (right panel: higher magnification of area indicated in middle panel).",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative CD11b+ myeloid cell content in colon (n=16) and tumors (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Anti-Gr1 immunostaining on normal colon (left panel) and a representative colon tumor section derived from an Apcfl/fl-Cdx2CreERT2 mouse (right panel: higher magnification of area indicated in middle panel).",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Relative CD11b+ MHCII- Gr1hi neutrophil (E) and CD11b+ MHCII- Gr1lo monocyte (F) content in colon (n=13) and tumors (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Immune cell contexture in healthy colon and colon tumors of Apcfl/fl-Cdx2CreERT2 mice. , Correlation of tumor T cell numbers to sample-matched tumor-derived neutrophil (left panel) and monocyte (right panel) numbers (n=16). relative content of individual cell types was determined in tissue-derived single cell suspension using cell type specific antibodies and FACS analysis.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "In vitro co-culture of activated T cells with increasing ratios of neutrophils, monocytes or macrophages. T cell proliferation index is numbers of proliferated T cells after three days of indicated co-culture condition relative to the number of proliferated T cells when cultured alone. CD4+ and CD8+ T cells were derived from lymph nodes of wild-type mice. Neutrophils, monocytes and macrophages were derived from colon tumors of Apcfl/fl-Cdx2CreERT2 mice. Each dot represents an individual neutrophil (n=4), monocyte (n=3) or macrophage (n=4) sample. Bars represent mean +/- SD.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Co-immunostaining for MMP9 (green) and S100A9 (red) on a representative tumor section derived from an Apcfl/fl-Cdx2CreERT2 mouse. Right panel shows a higher magnification of indicated area of the left panel.",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "mRNA expression levels of Mmp9 (C) or Tgfb1, Tgfb2 and Tgfb3 (D) in indicated FACS sorted cell types isolated from mouse colon tumors (n=4). Data are derived from RNA-sequencing and are displayed as reads per kilo base per million mapped reads (rpkm).",
    "ncbi_link": "Mmp9: 17395
Tgfb1: 21803
Tgfb2: 21808
Tgfb3: 21809"
  },
  {
    "caption": "Evaluation of TGFβ signaling activity in mouse colon tumors after four consecutive daily injections of hosts with 40mg/kg of the MMP2/9-inhibitor SB3-CT (MMPi). , Co-immunostaining for pSMAD3 (green) and IGFBP7 (magenta) on representative tumor-containing colon sections derived from Apcfl/fl-Cdx2CreERT2 mice treated with vehicle (A) MMPi (B).",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "effect of in vivo TGFBRi and MMPi treatment of mice for two weeks on colon tumor formation. Apcfl/fl-Cdx2CreERT2 mice were treated with Tamoxifen and, one day post treatment, injected with either MMPi (n=10) or the TGFBRi SB431542 (n=10) at 40mg/kg for two weeks with five injections per week. Vehicle treated mice: n=11. Average tumor size per mouse was assessed during colon resection one week after the end of treatments (E).",
    "ncbi_link": "Apc: 11789
Cdx2: 12591
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "B. Immunoblot of parental wild-type (WT) and UPF3B mutant cell lines showing levels of proteins on the right. In 3BΔ2BD, a smaller UPF3B protein with deletion of amino acids 20-155 (UPF3BΔ20-155) is expressed. Relative Expression (Rel Exp) of this deletion protein as compared to the full-length UPF3B along with standard error of mean (SEM) are indicated below lane 2. UPF3B antibody recognizes antigen outside the deleted region in 3BΔ2BD. HNRNPA1 is used as a loading control. ND = UPF3B levels not determined.",
    "ncbi_link": "3B: 65109
UPF3B: 65109"
  },
  {
    "caption": "C. Cumulative Distribution Function (CDF) plots of PTC+ isoforms and PTC- isoforms from the same set of genes. X-axis represents fold change in 3BΔ2BD versus WT cells each with control knockdown (siNC). Number of transcripts in each set (n) and p-value from Kolmogorov-Smirnov (KS) test comparing the two distributions are shown.",
    "ncbi_link": "3B: 65109"
  },
  {
    "caption": "D. Bar plots from isoform specific RT-qPCR analysis showing average fold change (y-axis) of PTC+ and PTC- isoforms from genes indicated on the bottom in WT and the two UPF3B mutant cells identified in the legend on the top right. For each isoform, levels in mutant cells are compared to the levels in WT cells (set to 1).",
    "ncbi_link": "UPF3B: 65109"
  },
  {
    "caption": "E. Cumulative Distribution Function (CDF) plots of NMD+ isoforms and NMD- isoforms. X-axis represents fold change in 3BΔ2BD versus WT cells each with control knockdown (siNC). Number of transcripts in each set (n) and p-value from Kolmogorov-Smirnov (KS) test comparing the two distributions are shown. F. Cumulative Distribution Function (CDF) plots of PTC+ isoforms and PTC- isoforms from same set of genes. X-axis represents fold change in UPF1 knockdown (siUPF1) versus control knockdown (siNC) in 3BΔ2BD cells. Number of transcripts in each set (n) and p-value from Kolmogorov-Smirnov (KS) test comparing the two distributions are shown. G. Cumulative Distribution Function (CDF) plots of NMD+ isoforms and NMD- isoforms. X-axis represents fold change in UPF1 knockdown (siUPF1) versus control knockdown (siNC) in 3BΔ2BD cells. Number of transcripts in each set (n) and p-value from Kolmogorov-Smirnov (KS) test comparing the two distributions are shown.",
    "ncbi_link": "UPF1: 5976
3B: 65109"
  },
  {
    "caption": "A. Immunoblots showing levels of proteins on the right in input or FLAG immunoprecipitates (IP) from WT and UPF3B mutant cells expressing endogenously FLAG-tagged UPF1 protein as indicated above each lane. The presence of RNase A during FLAG-IP is indicated above each lane.",
    "ncbi_link": "FLAG: 
UPF1: 5976
UPF3B: 65109"
  },
  {
    "caption": "B. Immunoblots showing levels of proteins (right) in input and IP with normal rabbit IgG (IgG-IP) or antibody targeting EIF4A3 (EIF4A3-IP) from WT and UPF3B mutant cells.",
    "ncbi_link": "UPF3B: 65109"
  },
  {
    "caption": "C, D. CDF plots of (C) PTC+ and PTC-isoforms, (D) NMD+ and NMD- isoforms. X-axis represents fold change upon UPF3A knockdown (siUPF3A) versus negative control knockdown (siNC) in WT cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot. E, F. CDF plots of (E) PTC+ and PTC-isoforms, (F) NMD+ and NMD- isoforms. X-axis represents fold change upon UPF3A knockdown (siUPF3A) versus negative control knockdown (siNC) in 3BΔ2BD cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot. G, H. CDF plots of UPF3B-dependent (G) and -independent (H) PTC+ isoforms and their respective PTC- isoforms. X-axis represents fold change upon UPF3A knockdown (siUPF3A) versus negative control knockdown (siNC) in 3BΔ2BD cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot.",
    "ncbi_link": "UPF3A: 65110
3B: 65109
UPF3B: 65109"
  },
  {
    "caption": "I. CDF plots of UPF3B-dependent and UPF3B-independent NMD+ isoforms as compared to NMD- isoforms. X-axis represents fold change upon UPF3A knockdown (siUPF3A) versus negative control knockdown (siNC) in 3BΔ2BD cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot.",
    "ncbi_link": "UPF3A: 65110
3B: 65109
UPF3B: 65109"
  },
  {
    "caption": "J. Bar plot showing average fold change as measured by isoform specific RT-qPCR of PTC+ and PTC- isoform from genes indicated on the bottom in WT and two independent clones of 3AKO, 3BΔ2BD, 3BKO, and 3DKO cells. Relative levels from each replicate are shown by white circles. Error bars indicate standard errors of means.",
    "ncbi_link": "3A: 65110
3B: 65109"
  },
  {
    "caption": "B. Immunoblot showing levels of EJC and UPF proteins (on the right) in input or FLAG-IP samples from 3DKO#2 cells stably expressing different FLAG-tagged proteins indicated above each lane. D. Immunoblot showing EJC/UPF proteins (on the right) in input or FLAG-IP samples from 3DKO#2 cells stably expressing FLAG-tagged proteins given above each lane (hUPF3B = human UPF3B; hUPF3B-h3AC = human UPF3B protein with C-terminal domain from human UPF3A; hUPF3B-m3AC = human UPF3B protein with C-terminal domain from mouse UPF3A).",
    "ncbi_link": "UPF3A: 65110
UPF3A: 67031
UPF3B: 65109"
  },
  {
    "caption": "A. Northern blots showing levels of β-globin reporter mRNAs in wild-type HeLa Tet-off cells and UPF3B knockout HeLa Tet-off cells. β39 is a tetracycline (Tet)-inducible reporter with a PTC at codon 39 whose levels are shown at different timepoints after transcriptional shut-off (chase) as indicated above each lane. β-GAP is a stable, constitutively-expressed, longer β-globin mRNA used as transfection control. Proteins overexpressed (OE) in each condition are indicated on top and reporter mRNA half-lives (t1/2) along with standard errors of means are on the bottom.",
    "ncbi_link": "β-GAP: 2705
β-globin: 3043
β39: 3043
UPF3B: 65109"
  },
  {
    "caption": "C. Northern blot showing steady-state levels of β39 NMD reporter and β-GAP control in HeLa Tet-off UPF3B knockout cells upon transient overexpression of wild-type UPF3 proteins or different UPF3A chimeric proteins indicated above each lane. Below each lane, relative fold-change (Rel FC) indicates β39 reporter levels (normalized to β-GAP control) as compared to the normalized β39 reporter levels in UPF3B expressing cells.",
    "ncbi_link": "β-GAP: 2705
β39: 3043
UPF3A: 65110
UPF3B: 65109"
  },
  {
    "caption": "A, B. CDF plots of (A) PTC+ and PTC-isoforms, (B) NMD+ and NMD- isoforms. X-axis represents fold change upon UPF1 knockdown (siUPF1) versus negative control knockdown (siNC) in 3DKO#2 cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "D, E. CDF plots of UPF3A/3B-independent (UPF3A/3B-indep., D) and -dependent (UPF3A/3B-dep., E) PTC+ isoforms and their respective PTC- isoforms. X-axis represents fold change upon UPF1 knockdown (siUPF1) versus negative control knockdown (siNC) in 3DKO#2 cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "F. CDF plots of UPF3A/3B-dependent (UPF3A/3B-dep.), UPF3A/3B-independent (UPF3A/3B-indep.) NMD+ isoforms and NMD- isoforms. X-axis represents fold change upon UPF1 knockdown (siUPF1) versus negative control knockdown (siNC) in 3DKO#2 cells. Number of transcripts in each set (n) and p-value from KS test comparing the two distributions are shown on each plot.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "A, B. Western blots showing levels of EJC proteins or HNRNPA1 (control) in input, IgG IP or EIF4A3 IP following overexpression (OE) of CASC3 wild-type (WT) and EJC binding deficient (HDAA) mutant proteins in (A) HeLa Tet-off cells, and (B) 3BKO#3 HeLa Tet-off cells. Ramps above lanes indicate expression levels of the CASC3 proteins.",
    "ncbi_link": "CASC3: 22794
3B: 65109"
  },
  {
    "caption": "C. Western blots showing levels of EJC/UPF proteins and HNRNPA1 in input and FLAG followed by EIF4A3 tandem IP from HCT116 cells expressing the FLAG-tagged endogenous protein indicated above each lane. Quantifications of UPF3B and CASC3 protein enrichment from two replicates are shown at the bottom.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "I. Bar plots showing fold changes measured by isoform specific RT-qPCR of PTC+ and PTC- isoform from genes indicated on the bottom in WT and CASC3-KO HCT116 cells. Relative levels from each replicate are shown by white circles. Error bars indicate standard error of means.",
    "ncbi_link": "CASC3: 22794"
  },
  {
    "caption": "(B) Inhibition of autophagy blocks HMGB1 translocation. Cells were pretreated as indicated with 100 nM wortmannin or 10 µM Ly294002 for 1 h or ATG5-specific shRNA for 48 h and were stimulated with starvation (HBSS) for 3 h and immunostained with HMGB1- or LC3-specific antibody and Hoechst 33342. The mean nuclear/cytosolic HMGB1 intensity and LC3 punctae per cell were determined by imaging cytometric analysis. A representative Western blot of ATG5 level after shRNA and HMGB1 staining is depicted (right). In parallel, the indicated cells were transfected with GFP-LC3 plasmid and assayed for autophagy by quantifying the percentage of cells with GFP-LC3 punctae. *, P < 0.05, **, P < 0.005, and ***, P < 0.0005 versus HBSS group; n = 3. Ctrl, control.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(C) Knockdown of ATG5 inhibits LC3-II expression. Western blot analysis of LC3-I/II expression in Panc02 cells under the conditions described in B. Actin was used as a loading control.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(D) Hmgb1−/− does not influence ATG5 staining. Hmgb1−/− and Hmgb1+/+ MEFs were immunostained with HMGB1-specific antibody (green), ATG-5-specific antibody (red), and Hoechst 33342 (dark blue). Representative images are depicted in the right panels.",
    "ncbi_link": "Hmgb1: 15289"
  },
  {
    "caption": "(G) Antioxidant and SOD RNAi limit starvation-induced autophagy and HMGB1 translocation. Panc2.03 cells were pretreated with the antioxidant (NAC) at the indicated concentrations for 1 h or with SOD1 or SOD2 siRNA for 48 h. Then cells were starved (HBSS) for 3 h and analyzed by imaging cytometry to determine the mean nuclear/cytosolic HMGB1 intensity and LC3 punctae per cell. *, P < 0.05; **, P < 0.005; and ***, P < 0.0005 versus HBSS group; n = 3. A representative Western blot for SOD1 and SOD2 level after siRNA is depicted here.",
    "ncbi_link": "SOD1: 6647
SOD2: 6648"
  },
  {
    "caption": "(A) HMGB1 knockout inhibits LC3 punctae formation. HMGB1−/− and HMGB1+/+ MEFs were treated with autophagic stimuli as indicated, and LC3 punctae formation was detected by LC3 antibody or GFP-LC3 as described in Materials and methods. *, P < 0.05; **, P < 0.005; and ***, P < 0.0005 versus Hmgb1+/+ group; n = 3. UT, untreated. (B) Representative images of LC3 punctae in Hmgb1−/− and HMGB1+/+ MEFs with the indicated treatments are depicted. The percentage of cells showing accumulation of LC3 punctae was reported in A.",
    "ncbi_link": "HMGB1: 15289
Hmgb1: 15289"
  },
  {
    "caption": "(C) Analysis of LC3 processing by autophagy in the presence or absence of lysosomal protease inhibitors pepstatin A (pepA) at 10 µg/ml and E64D at 10 µg/ml after starvation treatment for 3 h. **, P < 0.05 versus Hmgb1+/+ group; n = 3. Actin was used as a loading control. AU, arbitrary units.",
    "ncbi_link": "Hmgb1: 15289"
  },
  {
    "caption": "(D) Up-regulation of HMGB1 protein expression restores starvation-induced autophagy. Hmgb1−/− MEFs were transfected with HMGB1 plasmid or empty vector and then were treated with starvation for 3 h. LC3 punctae formation was assayed by imaging cytometric analysis. **, P < 0.05 versus vector group; n = 3. Non, nontransfected.",
    "ncbi_link": "HMGB1: 15289"
  },
  {
    "caption": "(E) Analysis of p62 processing by autophagy in the presence or absence of lysosomal protease inhibitors pepstatin A at 10 µg/ml and E64D at 10 µg/ml after starvation treatment for 3 h. **, P < 0.005 and ***, P < 0.0005 versus Hmgb1+/+ group; n = 3. Representative images are depicted (left).",
    "ncbi_link": "Hmgb1: 15289"
  },
  {
    "caption": "(F) Ultrastructural features in Hmgb1−/− and Hmgb1+/+ MEFs with or without starvation (HBSS for 3 h) treatment (a-e point to autophagosomes and autolysosomes). Data are means ± SEM.",
    "ncbi_link": "Hmgb1: 15289"
  },
  {
    "caption": "Inhibition of autophagy by cytoplasmic HMGB1. Hmgb1−/− and Hmgb1+/+ MEFs were enucleated by centrifugation after cytochalasin B treatment as described in Materials and methods and then were treated with HBSS for 3 h, and LC3 punctae formation was detected by a confocal microscope. (A) Representative images of LC3 punctae (white arrows) and HMGB1 (red arrows) in cytoplasts of Hmgb1−/− and Hmgb1+/+ MEFs are depicted. (B) The percentage of cells showing accumulation of LC3 punctae was reported (*, P < 0.05; n = 3). Data are means ± SEM.",
    "ncbi_link": "Hmgb1: 15289
HMGB1: 15289"
  },
  {
    "caption": "(A) MEK inhibitors block starvation-induced p-ERK and Bcl-2. HMGB1−/− and HMGB1+/+ MEFs were starved in the presence or absence of 10 µM U0126 and 20 µM PD98059 for 6 h. Protein expression levels were assessed as indicated by co-IP or Western blotting.",
    "ncbi_link": "HMGB1: 15289"
  },
  {
    "caption": "(B) Knockout of HMGB1 limits the disassociation of the Bcl-2-Beclin1 complex during treatment with autophagic stimuli. HMGB1−/− and HMGB1+/+ MEFs were starved in the presence or absence of 10 µM U0126 for 3 h. Protein expression levels were then assayed as indicated by co-IP or Western blotting.",
    "ncbi_link": "HMGB1: 15289"
  },
  {
    "caption": "(D) HMGB1 direct interactions with Bcl-2 are dependent on Beclin1. Knockdown of Beclin1 and Bcl-2 by siRNA in HMGB1 wild-type MEFs was performed, and protein expression levels were then assayed as indicated by co-IP or Western blotting. Ctrl, control.",
    "ncbi_link": "Bcl-2: 12043
Beclin1: 56208"
  },
  {
    "caption": "(A) The C106 mutation (C106S) of HMGB1 impairs its nuclear localization. Hmgb1−/− MEFs were transfected with wild-type and cysteine mutant HMGB1-GFP plasmids as indicated and then were treated with 1 µM rapamycin for 12 h or starved (HBSS) for 3 h. The mean nuclear (Nuc) and cytosolic (Cyt) HMGB1 intensity per cell was analyzed by imaging cytometric analysis. *, P < 0.05 versus HMGB1+/+ group; n = 3. Representative images of HMGB1 location are shown on the left (green, HMGB1; blue, nucleus). The right panel is a schematic diagram of HMGB1 structure illustrating the basic A box and B box as well as the acidic C-terminal domain, with the cysteine mutation locations identified.",
    "ncbi_link": "Hmgb1: 15289"
  },
  {
    "caption": "(B and C) Cytoplasmic HMGB1 enhances autophagy and limits apoptosis. HMGB1−/− MEFs were transfected with wild-type or cysteine mutant HMGB1-GFP plasmids as indicated and then were starved (HBSS) for the indicated time. In a parallel experiment, Hmgb1+/+ MEFs were pretreated with 5 mM ethyl pyruvate (EP) for 2 h and then starved as indicated. LC3 punctae formation was assayed by imaging cytometric analysis (B)",
    "ncbi_link": "HMGB1: 15289
Hmgb1: 15289"
  },
  {
    "caption": "(B and C) Cytoplasmic HMGB1 enhances autophagy and limits apoptosis. HMGB1−/−MEFs were transfected with wild-type or cysteine mutant HMGB1-GFP plasmids as indicated and then were starved (HBSS) for the indicated time. In a parallel experiment, Hmgb1+/+MEFs were pretreated with 5 mM ethyl pyruvate (EP) for 2 h and then starved as indicated. Apoptosis was assayed by FACS (C) (C) as described in Materials and methods. *, P < 0.05 and **, P < 0.005; n = 3. UT, untreated. Non, nontransfection.",
    "ncbi_link": "HMGB1: 15289
Hmgb1: 15289"
  },
  {
    "caption": "(D) C23/C45 is required for the binding of HMGB1 to Beclin1. Hmgb1−/− MEFs were transfected with wild-type or cysteine mutant HMGB1-GFP plasmids as indicated and stimulated with starvation (HBSS) for 3 h. These cells were then assayed for protein expression levels as indicated by IP or Western blotting. Blots are representative of three independent experiments with similar results.",
    "ncbi_link": "HMGB1: 15289
Hmgb1: 15289"
  },
  {
    "caption": "(F) Knockdown of Beclin1 by siRNA inhibits autophagy under conditions of HMGB1 translocation from the nucleus to the cytosol. Cells were stimulated with HBSS, rapamycin (Rap), rotenone (Rot), or thenoyltrifluoroacetone (TTFA) for 3 h or 12 h, and LC3 punctae formation was assayed as indicated. **, P < 0.005 versus Beclin1 shRNA group; n = 3. Ctrl, control. Data are means ± SEM.",
    "ncbi_link": "Beclin1: 56208"
  },
  {
    "caption": "(A and B) Knockdown of Beclin1 in MEFs by shRNA inhibits exogenous HMGB1-induced autophagy. Cells as indicated were stimulated with 1 µg/ml HMGB1 protein (rHMGB1) for 24 h, LC3 punctae formation (arrows) was assayed by immunofluorescence (B; n = 3; *, P < 0.05).",
    "ncbi_link": "Beclin1: 56208"
  },
  {
    "caption": "(C and D) Knockdown of Beclin1 in MEFs by shRNA inhibits HBSS-induced autophagy with and without pUNO1-HMGB1 transfection. Cells as indicated were stimulated with Earle's balanced salt solution for 3 h, and LC3 punctae formation (arrows) was assayed by immunofluorescence (D; n = 3; *, P < 0.05). Data are means ± SEM.",
    "ncbi_link": "Beclin1: 56208
HMGB1: 15289"
  },
  {
    "caption": "Expression of HMGB1 or the C106S mutant, but not C23S and C45S mutants, restore autophagic flux in Hmgb1−/− MEFs. (A) HMGB1−/− MEFs were transfected with wild-type (WT) or the cysteine mutant HMGB1-GFP plasmids as indicated, starved (HBSS) for 3 h in the presence or absence of 100 nM bafilomycin A1, and then immunostained with LAMP2-specific antibody/Alexa Fluor 594 secondary antibody (shown in red), LC3-specific antibody/Alexa Fluor 647 secondary antibody (shown in green), and Hoechst 33342 (shown in blue). Images were acquired digitally from a randomly selected pool of 10-15 fields under each condition. (B) Quantitative analysis of the percentage of LAMP2/LC3 colocalization was detected by Image-Pro Plus 5.1 software. Data are means ± SEM.",
    "ncbi_link": "HMGB1: 15289
Hmgb1: 15289"
  },
  {
    "caption": "A-F (A, B, D-F) RNA levels determined by RT-qPCR. Results are presented as mean ± SD,n = 10. P-values are indicated on the top of each plot. (C) Spearman correlation suggests an in vivo positive correlation between the expressions of H19 and Igf1r in a statistically significant manner. Spearman correlation coefficient, P-values, and sample numbers are marked on the top left of the plot.",
    "ncbi_link": "H19: 283120
Igf1r: 3480"
  },
  {
    "caption": "A-D Endometrial stromal cells from patients #166 and #80 were each transfected with a mixture of siCon (control siRNA) and microRNA inhibitor control (iCon), siH19 and iCon, or siH19 and iLet7 (let-7-specific inhibitor). RNA and proteins were analyzed at 48 h post-transfection. Combined results from the two patient cells are presented.",
    "ncbi_link": "H19: 283120
let-7: RF00027
Let7: RF00027"
  },
  {
    "caption": "A-D Endometrial stromal cells from patients #166 and #80 were each transfected with a mixture of siCon (control siRNA) and microRNA inhibitor control (iCon), siH19 and iCon, or siH19 and iLet7 (let-7-specific inhibitor). Western blot gels from #166 cells are shown in (C). Quantitation of Western blots combining both patient cells are shown in (D).",
    "ncbi_link": "H19: 283120
let-7: RF00027
Let7: RF00027"
  },
  {
    "caption": "E-H Endometrial stromal cells from patients #98 and #212S were each transfected with empty vector or pH19. RNA and proteins were analyzed 48 h post-transfection. Combined results from the two patient cells are presented.",
    "ncbi_link": "H19: 283120"
  },
  {
    "caption": "E-H Endometrial stromal cells from patients #98 and #212S were each transfected with empty vector or pH19. RNA and proteins were analyzed 48 h post-transfection. Combined results from the two patient cells are presented. Western blot gels from #98 cells are shown in (G). Quantitation of Western blots combining both patient cells are shown in (H).",
    "ncbi_link": "H19: 283120"
  },
  {
    "caption": "A-F The indicated cells were transfected with siCon, siH19, empty vector, or pH19. RNA, cell viability (as indicated by viable cell numbers), and caspase activity (as a readout for apoptosis) were analyzed 48 h post-transfection. Combined results from two patient cells in each group are presented.",
    "ncbi_link": "H19: 283120"
  },
  {
    "caption": "G E2 stimulates H19 expression in endometrial stromal cells. Endometrial stromal cells #166 and #98 were stimulated with E2 (+) or vehicle (−) for 48 h, followed by RT-qPCR analysis of RNA extracted from the cells. Results combining two patient cells are shown.",
    "ncbi_link": "H19: 283120"
  },
  {
    "caption": "Combined IF and DNA FISH for RAD54 (IF) and telomeres (FISH) in U2OS-TRF1-FOK1-WT or U2OS-TRF1-FOK1-D450A (nuclease dead) cells. Cells were treated as in E immediately prior to staining. Scale bars = 10 µm Quantification of data from F. RAD54 foci were detected using particle analysis in Fiji. At least a total of 300 cells were counted from 3 repeated experiments. Values shown are mean±sem. Values were compared using Kruskal-Wallis test followed by Dunn's multiple comparison test. Quantification of data from F. RAD54 foci were detected using particle analysis in Fiji. Cells were counted as positive if they counted 8 or more RAD54 foci that colocalized with telomeres. Values shown are mean±sem of n=3 biological replicates. Values were compared using standard two-way ANOVA followed by Sidak's multiple comparison test.",
    "ncbi_link": "FOK1: 
TRF1: 7013"
  },
  {
    "caption": "Combined IF and DNA FISH for RAD51 (IF) and telomeres (FISH) in SaOS2 or HuO9 cells. Cells were transfected with 20nM siRAD54#2 for 48 hours immediately prior to staining. Scale bars = 10 µm Quantification of A. A cell was counted as positive it is contained at least 1 colocalization event between RAD51 and telomeres. At least 100 cells were counted per condition per repeat, n=3. Values shown are mean±sd. Data were compared using standard two-way ANOVA followed by Sidak's multiple comparison test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "ChIP for telomeric DNA associated with RAD51. DNA dot blot probed with DIG labeled telomere probe or Alu probe. HuO9 cells were transfected with 20nM siRAD54 #2, or 15µg myc-TRF2 for 72 hours prior to immunoprecipitation with RAD51 antibody (Mock, siRAD54 conditions) or myc antibody (myc-TRF2 positive control). Quantification of (CCCTAA)4 dot blot performed in C. IP values were normalized to loading (IP/input) and then normalized to mock control. Values shown are mean±sd of n=3 biological replicates. Values were compared using two-tailed unpaired student's t-test.",
    "ncbi_link": "myc: 
RAD54: 8438
TRF2: 7014"
  },
  {
    "caption": "Combined IF and DNA FISH for GFP (IF) and telomeres (FISH) in SaOS2 and HuO9 cells. Cells were forward transfected with Polη-GFP, and then after 24 hours transfected with 20nM siRAD54#2. Cells were stained for GFP and telomeres 48 hours after siRNA transfection. Scale bars = 10 µm Quantification of data in F. GFP negative cells were excluded from analysis. Cells were considered positive if they showed 1 or more colocalization events between GFP (Polη) and telomeres. At least 50 GFP positive cells were counted per condition per repeat, n=3. Values shown are mean±sd. Values were compared using standard two-way ANOVA followed by Sidak's multiple comparison test.",
    "ncbi_link": "GFP: 
Polη: 
RAD54: 8438"
  },
  {
    "caption": "Representative images of combined EdU staining (Click-it) and DNA FISH for telomeres. HuO9 or SaOS2 cells were transfected with 20nM siRAD54#2 (representative images for siRAD54#1 not shown) for 48 hours followed by a 1.5 hr pulse of EdU. Pan-nuclear EdU stain represents S-phase cells. White arrows indicate non-S-phase cells containing EdU colocalizing with telomeres. Scale bars = 10 µm Quantification of data shown in A. HuO9 or SaOS2 cells were mock transfected or transfected with 20nM siRAD54#1 or 20nM siRAD54#2 for 48 hours followed by a 1.5 hr pulse of EdU. Cells with pan-nuclear EdU signal or greater than 8 EdU foci were excluded from analysis as S-phase cells. Non-S-phase cells were considered positive if they contained at least one EdU foci colocalizing with telomeres. Data were normalized to mock condition for each repeat. At least 100 non-S-phase cells were counted per condition per repeat, n=3. Values shown are mean±sd. Data were analyzed using two-way ANOVA followed by Dunnett's multiple comparison test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Representative DNA dot blot from C-circle assay on HuO9 cells, either mock transfected or transfected with 20nM siRAD54#2 for 48 hours. Quantification of C-circle assay in C. Signal was quantified with densitometry, background (- Φ29) was subtracted and signal was normalized to mock. N=5 biological replicates values shown are mean±sd. Conditions were analyzed using unpaired two-tailed student's t-test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Representative images of combined IF and DNA FISH for PML (IF) and telomeres (FISH). HuO9 or SaOS2 cells were mock transfected or transfected with 20nM siRAD54#2 for 48 hours. White arrows indicate large colocalization events. Blue arrows indicate small colocalization events. Scale bars = 10 µm Quantification HuO9 or SaOS2 cells were mock transfected or transfected with 20nM siRAD54#1 or 20nM siRAD54#2 for 48 hours. Cells were considered positive if they contained 1 large or 3 small colocalization events. At least 100 cells were counted per condition per repeat, n=3. Values shown are mean±sd. Data were analyzed using two-way ANOVA followed by Dunnett's multiple comparison test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Representative images of combined EdU staining (Click-it) and DNA FISH for telomeric DNA. HuO9 cells were forward transfected with 2µg empty vector (EV), RAD54-WT, RAD54-K189R, or S49E construct. After 24 hours, cells were transfected with 20 nM siRAD54#2 for 48 hours followed by a 1.5 hr pulse of EdU. White arrows indicate non-S-phase cells containing EdU colocalizing with telomeres. Scale bars = 10 µm Quantification of data shown in G. Non-S-phase cells were considered positive if they contained at least one EdU foci colocalizing with telomeres. Data were normalized to EV-Mock condition for each repeat. At least 100 non-S-phase cells were counted per condition per repeat, n=4 for EV, WT, S49E, n=3 for K189R. Values shown are mean±sd. Data were analyzed using two-way ANOVA followed by Sidak's multiple comparison test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Representative images of combined IF and DNA FISH for BLM (IF) and telomeres (FISH). HuO9 cells were transfected with 20nM siRAD54#2 for 48 hours. Scale bars = 10 µm Quantification of data shown in A. Cells were counted positive if they contained at least 1 colocalization event between BLM and telomeres. Data were normalized to mock condition of each repeat. At least 100 cells per condition per repeat were counted, n=3. Values shown are mean±sd. Conditions were analyzed using unpaired two-tailed student's t-test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Representative images of IF-DNA FISH for MUS81 and telomeres. HuO9 cells were transfected with 20nM siRAD54 #2 for 48 hours prior to staining. Scale bars = 10 µm Quantification of data shown in C. Cells were counted positive if they contained at least 1 colocalization event between MUS81 and telomeres. At least 100 cells per condition were counted per repeat. n=5, values shown are mean±sd. Conditions were analyzed using unpaired two-tailed student's t-test.",
    "ncbi_link": "RAD54: 8438"
  },
  {
    "caption": "Quantification of data shown in G. Anaphases were scored from 4 independent experiments (mock), or 3 independent experiments (remaining conditions). Anaphases were considered positive for UFB if there was PICH staining between DAPI bodies. Single knockdown conditions had >50 anaphases scored. Combined knockdown conditions had >88 anaphases scored. Values shown are mean±sd. Conditions were compared using one-way ANOVA followed by Dunnett's multiple comparison test. Quantification of data shown in G. Number of PICH stained UFBs counted per anaphase. Values shown are total counts over 3 independent experiments, shown mean±sem. Total number of anaphases per condition were as follows: Mock n=134, siBLM/siSLX4 n=90, siRAD54/siSLX4 n=96, siRAD54/siBLM/siSLX4 n=88. Conditions were compared using Kruskal-Wallis test followed by Dunn's multiple comparison test.",
    "ncbi_link": "BLM: 641
RAD54: 8438
SLX4: 84464"
  },
  {
    "caption": "Representative images of UFB staining for TRF2 in HuO9 cells. Cells were transfected with 20nM siRAD54#2 alone or cotransfected siRAD54#2 and siSLX4 for 72 hours prior to staining. Scale bars = 10 µm",
    "ncbi_link": "RAD54: 8438
SLX4: 84464"
  },
  {
    "caption": "Quantification of data shown in J. Anaphases were scored from 3 independent experiments. A total of 90 anaphases were scored per condition. Values shown are mean±sd. Conditions were compared using one-way ANOVA followed by Dunnett's multiple comparison test. Quantification of micronuclei from HuO9 cells transfected with siRAD54#2 alone or siRAD54#2 cotransfected with siSLX4 for 48 hours. Micronuclei containing telomeric DNA were identified using DAPI and telomere FISH. Micronuclei were normalized to the number of nuclei counted. Values shown are mean±sd of n=3 biological replicates. Conditions were compared using one-way ANOVA followed by Dunnett's multiple comparison test.",
    "ncbi_link": "RAD54: 8438
SLX4: 84464"
  },
  {
    "caption": "(A) HeLa cells stably expressing GFP‐LC3B (left panel) or GFP‐GATE‐16 (right panel) were transfected with either non‐targeting siRNA (control siRNA) or a pool of LC3 siRNAs (A, B, C), using DharmaFect reagent. After 72 h interval, the cells were incubated for 2 h in EBSS medium in the absence or presence of 0.1 μM Baf A and subjected to western blot analysis after lysis with RIPA extraction buffer.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(C) HeLa cells stably expressing GFP‐GATE‐16 were transfected with non‐targeting siRNA or a pool of LC3 siRNAs and treated as in (A). The cells were subjected to immunostaining with anti‐p62 after fixation, and analysed by confocal microscopy. The GFP intensity of three independent experiments was measured as described in 'Materials and methods' (right panel). Scale bar: 20 μm.",
    "ncbi_link": "GATE‐16: 11345"
  },
  {
    "caption": "(A) HeLa cells stably expressing GFP‐GATE‐16 (left panel) or GFP‐LC3B (right panel) were transfected with either non‐targeting siRNA (control siRNA) or a pool of GABARAP siRNAs (GABARAP, GABARAPL1, and GATE‐16) using DharmaFect reagent. After 72 h interval, the cells were incubated for 2 h in EBSS medium in the absence or presence of 0.1 μM Baf A and subjected to western blot analysis after lysis with RIPA extraction buffer.",
    "ncbi_link": "GABARAP: 11337
GABARAPL1: 11337
GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(C) HeLa cells stably expressing GFP‐LC3B were transfected with non‐targeting siRNA or a pool of GABARAP siRNAs and treated as in (A). The cells were subjected to immunostaining with anti‐p62 after fixation, and analysed by confocal microscopy. The GFP intensity of three independent experiments was measured as described in 'Materials and methods' (right panel). Scale bar: 20 μm.",
    "ncbi_link": "GABARAP: 11337
LC3B: 81631"
  },
  {
    "caption": "(A) Bulk protein degradation was tested in HeLa cells that were transfected with non‐targeting siRNA (control siRNA), a pool of GABARAP/GATE‐16 siRNAs, or a pool of LC3 siRNAs. The rate of long‐lived protein degradation was measured in cells incubated in either αMEM (control) or EBSS (starvation) medium, in the presence or absence of 10 mM of 3‐MA, 72 h after siRNA transfection. Values expressing the protein degradation percentage are represented as the mean±s.d. of three determinations.",
    "ncbi_link": "GABARAP: 11337
GATE‐16: 11345"
  },
  {
    "caption": "(B) HeLa cells stably expressing GFP‐LC3B (left panel) or GFP‐GATE‐16 (right panel) were transfected with a pool of GABARAP/GATE‐16 siRNAs or a pool of LC3, respectively, and with non‐targeting siRNA. Seventy‐two hours after transfection, the cells were collected after 5 h of starvation and the relative level of GFP‐LC3B or GFP‐GATE‐16 was measured using flow cytometry. Values represent the mean±s.d. of three experiments.",
    "ncbi_link": "GABARAP: 11337
GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(A) HeLa cells stably expressing YFP‐Atg5 were transfected with non‐targeting siRNA (control siRNA), a pool of LC3 siRNAs, or a pool of GABARAP/GATE‐16 siRNAs using DharmaFect reagent. Seventy‐two hours after transfection, the cells were incubated for 2 h in EBSS medium, fixed, and immunostained with anti‐Atg16 antibodies. Quantification of Atg5 and Atg16‐labelled puncta structures from three independent experiments is presented on the right panel. Scale bar: 20 μm.",
    "ncbi_link": "Atg5: 9474
GABARAP: 11337
GATE‐16: 11345"
  },
  {
    "caption": "(B) HeLa cells stably expressing YFP‐Atg5 were treated as in (A) and monitored by live microscopy. Quantification of the lifespan of Atg5‐labelled puncta structures is presented. Mean±s.d. of three independent experiments is presented. *P0.05, **P0.001.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(C) YFP‐Atg5 cells were transfected with siRNA pool and starved as in (A). Cryo sections of fixed cells were immunolabelled using anti‐GFP antibodies and analysed by TEM as described in 'Materials and methods'. Quantification of the Atg5‐labelled structures size is presented at the right panel. *P0.05, **P0.001.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(A) Control HeLa cells and HeLa cells stably expressing GFP‐LC3B or GFP‐GATE‐16 were starved for 2 h in EBSS medium fixed and immunostained with anti‐Atg16 antibodies. Quantification of Atg16‐labelled puncta structures from three independent experiments is presented at the right panel. Arrowheads represent Atg‐16‐labelled puncta. Scale bar: 20 μm.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(B) HeLa cells stably expressing GFP‐LC3B (left panel) or GFP‐GATE‐16 (middle panel) were starved for 2 h in EBSS medium. The cells were fixed and their cryo sections were immunolabelled as in ( Figure 4B). Quantification of the size of GFP‐labelled structures (right panel) from three independent experiments is presented. *P0.05, **P0.001.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(A, B) Control HeLa cells and HeLa cells stably expressing GFP‐LC3B (A) or GFP‐GATE‐16 (B) were transfected with the reciprocal siRNA pools using DharmaFect reagent. After 72 h interval, the cells were incubated for 2 h in EBSS, subjected to immunostaining with anti‐Atg16 after fixation, and analysed by confocal microscopy. Quantification of cells containing Atg16 structures larger than 2 μm (A) or Atg16‐labelled puncta structures (B) from three independent experiments in comparison to control and to G to A mutants (D) is presented at the lower panel. Scale bar: 20 μm.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(C) HeLa cells stably expressing silent GFP‐LC3B or GFP‐GATE‐16 were transfected with their siRNA pools using DharmaFect reagent. After 72‐h interval, the cells were incubated for 2 h in EBSS medium and subjected to immunostaining with anti‐Atg16 and anti‐p62 antibodies followed by fixation. The cells were analysed by confocal microscopy. Arrows represent cells, which do not express GFP proteins whereas arrowheads represent cells, which express GFP‐proteins. Quantification of Atg16‐labelled puncta structures from three independent experiments is presented at the right panel. Scale bar: 20 μm.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(D) HeLa cells stably expressing GFP‐LC3BG120A or GFP‐GATE‐16G116Awere transfected with either pool of GABARAP/GATE‐16 siRNAs or LC3 siRNAs, respectively, and a non‐targeting siRNA. The cells were starved for 2 h, fixed, and immunostained with anti‐Atg16 and anti‐p62 antibodies. Quantification is presented in (A, B) at the lower panels. Scale bar: 20 μm.",
    "ncbi_link": "GABARAP: 11337
GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(E) HeLa cells stably expressing GFP‐LC3B (left panel) or GFP‐GATE‐16 (right panel) were transfected with the reciprocal siRNA pool or with non‐targeting siRNA and starved for 2 h in EBSS medium. The cells were fixed and their cryo sections were immuno‐labelled using anti‐GFP antibodies and analysed by TEM as described in 'Materials and methods'. Quantification of cells containing Atg16 structures larger than 2 μm (left panel) or the size of Atg16‐labelled structures (right panel) is presented.",
    "ncbi_link": "GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(A) Control HeLa cells and HeLa cells stably expressing GFP‐LC3B or GFP‐GATE‐16 were transfected with HsAtg4AC77A‐Myc‐His6. After 48 h interval, the cells were incubated for 2 h in EBSS, and subjected to immunostaining with anti‐Atg16 and anti‐myc followed by confocal microscopy analysis. Quantification of cells containing Atg16 structures larger than 2 μm from three independent experiments is presented at the right panel. Scale bar: 20 μm.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345
LC3B: 81631"
  },
  {
    "caption": "(B) HeLa cells were transfected with HsAtg4AC77A‐Myc‐His6 or empty vector (mock). After a 48 h interval, the cells were incubated for 2 h in EBSS, fixed, and their ultrathin sections were analysed by TEM as described in 'Materials and methods'. *P0.05.",
    "ncbi_link": "Atg4A: 115201"
  },
  {
    "caption": "(D) mRNA expression of Il-1β; n= 5(RD), 7(HFD), 7(HFD+AB), 3(RD+AB); CI 95%, Il-6; n= 5(RD), 5(HFD), 4(HFD+AB), 4(RD+AB); CI 95%, Tnf-α; n= 6(RD), 9(HFD), 4(HFD+AB), 5(RD+AB); CI 95% and Vegf-a; n= 6(RD), 5(HFD), 5(HFD+AB), 6(RD+AB); CI 95% in choroids.",
    "ncbi_link": "Il-1β: 16176
Il-6: 16193
Tnf-α: 21926
Vegf-a: 22339"
  },
  {
    "caption": "(J) mRNA expression of Il-1β; n= 5(RDxRDT), 4(HFDxHFDT), 5(HFDxRDT), Il-6; n= 5(RDxRDT), 4(HFDxHFDT), 4(HFDxRDT); CI 99%, Tnf-α; n= 5(RDxRDT), 4(HFDxHFDT), 4(HFDxRDT); CI 95% and Vegf-a; n= 5(RDxRDT), 4(HFDxHFDT), 5(HFDxRDT); CI 95% in choroids.",
    "ncbi_link": "Il-1β: 16176
Il-6: 16193
Tnf-α: 21926
Vegf-a: 22339"
  },
  {
    "caption": "Volcano plot representation of AFG3L2E408Q-FLAG interaction  partners. Mitochondria  isolated from  Flp-In HEK293T-REx cells expressing  AFG3L2E408Q-FLAG  were subjected to immunoprecipitation. Co-purifying proteins were identified by quantitative  mass spectrometry (MS) (n=5 independent experiments) followed by an unpaired two-sided t-test and permutation-based FDR estimation to correct for multiple testing (FDR<0.05. Significantly enriched MitoCarta 3.0 proteins are colored in red, gene names indicate previously verified AFG3L2 interactors  and TMBIM5  (GHITM, MICS1).",
    "ncbi_link": "FLAG: 
AFG3L2: 10939"
  },
  {
    "caption": "Representative immunoblot  of HeLa  wildtype (WT) cells transfected with scrambled siRNA (control) or siRNA targeting TMBIM5  and treated with the indicated drugs for 16 h. Control (0.1% DMSO), actinomycin D  (1 µM), venetoclax  (1 µM), A-1155463 (1 µM), staurosporine  (1 µM), thapsigargin  (2 µM). n=3 independent experiments.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "Representative immunoblot  of HeLa  WT and TMBIM5-/- cells transfected with scrambled siRNA (control) or siRNA targeting MCU  for 72 h. Where indicated samples were treated with staurosporine  (STS; 1 µM) for 16 h. (n=3 independent experiments).",
    "ncbi_link": "TMBIM5: 27069
MCU: 90550"
  },
  {
    "caption": "Viability  of WT and TMBIM5-/- cells (depleted of MCU  when indicated) after incubation with staurosporine  (STS; 0.1 µM) for 16 h. Cell viability was assessed cytofluorimetrically  monitoring NucView488 and RedDot2 staining  and expressed as percentage of all cells. n=3 independent experiments; two-tailed t-test; mean ±SD. A p-value of <0.05 was considered statistically significant.",
    "ncbi_link": "TMBIM5: 27069
MCU: 90550"
  },
  {
    "caption": "WT and TMBIM5-/- HeLa  cells were transfected with the indicated scrambled siRNA (control) and siRNA targeting MCU  for 48 h and incubated with staurosporine  (0.1 µM) for 16 h in the presence of Z-VAD-FMK  (50 µM) and epoxomicin  (1 µM) to prevent apoptosis. Cells were subjected to immunofluorescence  analysis with antibodies directed against cytochrome c (green) and TOMM20  (magenta). *Cells with cytosolic cytochrome c. (n=3 independent experiments; number of cells > 150 each experiment).",
    "ncbi_link": "TMBIM5: 27069
MCU: 90550"
  },
  {
    "caption": "Fluorescence (F) F/F0 ratio quantifications, where F0 is the average of the first ten seconds and F is the fluorescence peak measured after thapsigargin  (2 µM) administration (left panel). The right shows mtRED-GECO  ratio traces of HeLa  cells transfected with scrambled siRNA (control) and siRNA targeting TMBIM5. Each measurement was performed in at least 10 cells from 6 different preparations. Mean ±SD; two-tailed t-test. A p-value of <0.05 was considered statistically significant.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "Matrix pH  was measured with  Sypher3smito  in wildtye (WT) HeLa  cells transfected with scrambled siRNA (control) or siRNA targeting TMBIM5  for 72 h. The probe was calibrated in KRB buffer by the stepwise addition/removal of permeant weak acid. Each measurement was performed in at least 80 cells from 7 different preparations. Mean ±SD; two-tailed t-test. A p-value of <0.05 was considered statistically significant.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "Mitochondrial membrane potential was monitored with TMRM   in WT and TMBIM5-/- HeLa  cells. Fluorescent intensity was calculated as ratio to the value upon CCCP  addition (15 µM). Values are expressed as mean ±SD relative to control. Each measurement was performed in triplicate from 4 different preparations.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "Matrix pH  was measured with  Sypher3smito  in WT HeLa  cells transiently expressing TMBIM5  or TMBIM5D294K D325K for 24 h. The ratio of absorbance at 488 nm and 405 nm is shown in arbitrary units (a.u.). Each measurement was performed in at least 20 cells from 3 different preparations. Representative immunoblot  of WT HeLa  cells transfected with TMBIM5  or TMBIM5D294K D325K for 24 h (right panel). Mean ±SD; two-tailed t-test. A p-value of <0.05 was considered statistically significant.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "Alterations in mitochondrial  proteome in WT and TMBIM5-/- HeLa  cells upon depletion of AFG3L2. WT and TMBIM5-/- HeLa  cells were transfected with scrambled siRNA (control) or siRNA targeting AFG3L2  for 48 h. Proteins, which were downregulated in the absence of TMBIM5  and whose steady state levels was altered upon depletion of AFG3L2, were identified using a two-way ANOVA. An interaction p-value of 0.01 was used as a cutoff. Log2-transformed LFQ intensities of MitoCarta 3.0 proteins were Z-Score normalized and visualized in a hierarchical cluster analysis (Euclidean distance, complete method). The dendrogram is omitted. Proteins accumulating upon depletion of AFG3L2  (cluster 1, C1) and proteins whose steady state levels are decreased upon depletion of AFG3L2  (cluster 2, C2) are shown.",
    "ncbi_link": "AFG3L2: 10939
TMBIM5: 27069"
  },
  {
    "caption": "Representative immunoblot  of TMBIM5-/- HeLa  cells transfected with scrambled siRNA (control) or siRNA targeting AFG3L2  for 48 h. Samples were treated with the protein synthesis inhibitor cycloheximide  (CHX; 10 μg/ml) and collected at the indicated  time points (n=3 independent experiments).",
    "ncbi_link": "AFG3L2: 10939
TMBIM5: 27069"
  },
  {
    "caption": "Representative immunoblot  of WT HeLa  cells transfected with scrambled siRNA (control) and siRNA targeting AFG3L2  for 48 h, treated when indicated with oligomycin  (10 μM) for 16 h. Quantification of TMBIM5  levels is shown on the right panel. TMBIM5  levels in untreated WT cells was set to 1 (n=3 independent experiments; mean ±SD).",
    "ncbi_link": "AFG3L2: 10939"
  },
  {
    "caption": "TMBIM5  abundance determined by mass spectrometry  in WT HeLa  cells treated with oligomycin  (10 µM; 16 h) and depleted of AFG3L2  when indicated. n=5 independent experiments. P-value was calculated using a two-sided unpaired t-test. The central band of each box is the median value, and the box defines the 25th (lower) and 75th (higher) quantile. The whiskers represent the minimum and maximum value in the data excluding outliers (greater than 1.5 * inter quantile range distance to median - no outliers found here).",
    "ncbi_link": "AFG3L2: 10939"
  },
  {
    "caption": "Zoom in to selected clusters of hierarchical clustering of Z-Score normalized log2 LFQ intensities. Proteins that were significantly (FDR<0.05) accumulated between HeLa  WT and TMBIM5-/- cells after oligomycin  treatment (10 µM) for 16 h were clustered using Euclidean distance and the complete method on protein features. The figure shows identified cluster C4 and C5 with gene names and MitoCarta 3.0 localization  annotations. The row dendrogram is omitted.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "B, Same as in A, with the exception that cells expressing flag-praja2rm or praja2 deletion mutants (praja21-530, praja21-630 and praja2Δ530-630) were included in the analysis.",
    "ncbi_link": "flag: 
praja2: 9867"
  },
  {
    "caption": "E. Same as in C, with the exception that cells were co-transfected with flag-OFD1 vector and with control siRNA (siCNT) or siRNA targeting praja2. F. Quantitative analysis of the experiments shown in E. A mean value ± SD of three independent experiments is shown. Student's t test, *p<0,05. G ",
    "ncbi_link": "flag: 
OFD1: 8481
praja2: 9867"
  },
  {
    "caption": "C. HEK293 cells  transfected  with siRNAs were serum deprived, pre-treated with cycloheximide and stimulated with FSK at different time point. Lysates were immunoblotted for endogenous praja2 and OFD1. Hsp90 was used as loading control. D. Quantitative analysis of the experiments shown in C. A mean value ± SD of three independent experiments is shown. Student's t test * p<0,05; **<0,01 versus sipraja2 (+FSK) and basal values (0). E ",
    "ncbi_link": "praja2: 9867"
  },
  {
    "caption": "H. Immunoblot analysis of flag-OFD1 or flag-E97G mutant in HEK293 cells stimulated with  FSK as in C. I. Quantitative analysis of the experiments shown in H. A mean value ± SD of three independent experiments is shown. Student's t test, *p<0,05 versus E97G mutant (+FSK) and basal values (0). ",
    "ncbi_link": "flag: 
OFD1: 8481"
  },
  {
    "caption": "C. HEK293 cells expressing flag-OFD1 or flag-S735A were serum deprived and subjected to staining analysis for acetylated α-tubulin, flag and DRAQ5. Images were collected by super-resolution microscopy (upper panels). Where indicated, flag-OFD1 or flag-S735A was co-transfected  with cilia-APEX-GFP vector (middle panels). NIH3T3 expressing flag-OFD1 or flag-S735A were  stained with anti-ARL13B and anti-flag antibodies. D, E. Statistical analysis of the experiments shown in D. A mean value ± SD of three independent experiments is shown. For each experimental group, a minimum of 40 cilia were analyzed. Student's t test p***<0,001. F ",
    "ncbi_link": "flag: 
OFD1: 8481"
  },
  {
    "caption": "F. HEK293 cells  transiently transfected  with flag-OFD1 or flag-S735A were serum  deprived, treated with FSK (6 hours) and stained for flag, acetylated-tubulin and DRAQ5. G. Statistical analysis of the experiments shown in F. A mean value ± SD of three independent experiments is shown. Cells analysed for each experiment: 300 for NT, 80 for  flag-OFD1 and 80 for flag-S735A. Student's t test, p*<0,05, p**<0,01. H ",
    "ncbi_link": "flag: 
OFD1: 8481"
  },
  {
    "caption": "B. Confocal images of cilia  of the  neural tube cells in the wild-type, Ol-TBC1D31 KD, Ol-TBC1D31 KD + hTBC1D31, wild-type hOFD1, Ol-TBC1D31 KD + wild-type hOFD1, hOFD1S735A, Ol-TBC1D31 KD + hOFD1S735A, Ol-TBC1D31  KD + hOFD1S735D and Ol-TBC1D31  KD + hOFD1S735D + hpraja2rm stained  with anti-acetylated α-tubulin antibody (green) and DAPI (blue).",
    "ncbi_link": "OFD1: 8481
praja2: 9867
TBC1D31: 101172761
TBC1D31: 93594"
  },
  {
    "caption": "C, D, Currents from IHCs of control (C, P9) and Kir2.1-OE (D, P10) pre-hearing mice. Currents were elicited by using depolarizing and hyperpolarizing voltage steps, with a nominal increment of 10 mV, from a holding potential of −84 mV. Test potentials are shown next to some of the traces. Note that the large inward rectifier Kir2.1 current is only present in the IHC of the Kir2.1-OE mouse (D). The outward current is primarily carried by a delayed rectifier current IK. IK1 identifies the small inwardly rectifying K+ current normally expressed in IHCs. E, Steady-state current-voltage curves obtained from IHCs of control (P9-P11) and Kir2.1-OE (P9-P11) mice.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "F, G, Representative ∆F/F0 traces from the IHCs and GER of P7-P9 control (F) and Kir2.1-OE (G) mice in the presence of 0.3 mM Ca2+. Spontaneous ATP-dependent Ca2+ waves from the GER (green traces) were eliciting coordinated Ca2+ signals in the IHCs from both controls and Kir2.1-OE mice. For each genotype, two separate sets of recordings from 2 mice are shown (top and bottom right), with the top traces being linked to the images on the left: before [1], during [2] and after [3]) the generation of a large Ca2+ wave from the GER. For details about the frequency and duration of the Ca2+ waves, and the number of mice and recordings see Fig EV3. All recordings were obtained at body temperature. Traces are computed as pixel averages of regions of interest centred on IHCs.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "C, Peak-to-peak MET current-voltage curves from P6-P7 apical-coil IHCs of 7 control (12 IHCs) and 3 littermates Kir2.1-OE mice (7 IHCs). Recordings were obtained by mechanically stimulating the hair bundles of IHCs at the same time as stepping their membrane potential from −124 mV to +96 mV in 20 mV increments. The two sets of data are not significantly different: P = 0.6320, 2-way ANOVA.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "C, Peak-to-peak MET current-voltage curves from P8-P9 apical-coil IHCs of 12 control (17 IHCs) and 13 littermates Kir2.1-OE mice (24 IHCs). The two sets of data are significantly different: P < 0.0001, 2-way ANOVA.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "J, Example of FM1-43 uptake by IHCs from P11 control (top) and Kir2.1-OE (bottom) mice, showing the lack of fluorescence labelling in the latter, which is an indication of the lack of MET channels open at rest at this stage in the IHCs overexpressing the Kir2.1 channels. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "A, B, Scanning electron microscope (SEM) images showing the IHC hair bundle structure in the apical coil of the cochlea of P11 control (A) and P8-P11 Kir2.1-OE (B) mice. Control IHCs and the large majority of P8 IHCs from Kir2.1-OE mice show a normal hair bundle structure composed of three rows of stereocilia: tall, intermediate and short (arrows). From about P9 in Kir2.1-OE mice, some IHCs start to lose the third row of stereocilia (arrowheads) and some already exhibit some fusion of the stereocilia (asterisk). These changes in hair-bundle structure became more prominent at P11. At least 3 mice for each genotype were used. In these panels and those below, asterisks are used to define some of the abnormal hair bundles.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "C, D, SEM images of both IHCs and OHCs from the cochlea of P26 control (C, upper panel) and P26 Kir2.1-OE (D, upper panel) mice. Lower panels show a higher-magnification view of the hair bundle of IHCs from both genotypes, highlighting the profound disruption of the stereocilia in IHCs overexpressing Kir2.1 channels. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "A,B, Maximum intensity projections of confocal z-stacks showing images of the hair bundles from apical-coil IHCs of P6 and P11 control (A) and Kir2.1-OE (B) mice immunostained with antibodies against MYOSIN VI (blue) and EPS8 (magenta). At least 3 mice for each genotype were used. In all panels (A-D), stereocilia are labelled with phalloidin (green). Note that despite the disrupted hair-bundle structure in the IHCs overexpressing Kir2.1 channels; the stereocilia retained a normal distribution of these bundle proteins. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "C,D, Confocal images of the hair bundles of P11 IHCs from control (C) and Kir2.1-OE (D) mice immunostained with antibodies against MYOSIN XV isoform 1 (blue) and WHIRLIN (magenta). In all panels (A-D), stereocilia are labelled with phalloidin (green). Note that despite the disrupted hair-bundle structure in the IHCs overexpressing Kir2.1 channels; the stereocilia retained a normal distribution of these bundle proteins. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "A,B, Maximum intensity projections of confocal z-stacks showing the IHCs of the apical cochlear region from control (A) and Kir2.1-OE (B) pups with the females being in the continuous presence of DOX in the drinking water from conception up to when the pups were P5 (upper panels). Middle and bottom panels show IHCs at P7 and P14 following the removal of DOX at P5 for both control (A) and Kir2.1-OE mice (B). IHCs were stained with antibodies against the K+ channel Kir2.1 (green) and Myosin 7a (Myo7a, blue: cell marker). Note that after 2 days following the removal of DOX, Kir2.1overexpression was already largely downregulated. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "H,I, Maximum intensity projections of confocal z-stacks showing images of the hair bundles from apical-coil IHCs of P14 control (H) and Kir2.1-OE (I) mice stained with phalloidin. DOX was removed from the mother's drinking water when the pups were P5. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "J,K, SEM images showing the normal structure of the hair bundles of the IHCs in the apical coil of the cochlea of P14 control (J) and P14 Kir2.1-OE (K) mice. DOX was removed from the mother's drinking water when the pups were P5. Note that the morphological profile of the hair bundles in IHCs is comparable between control and Kir2.1-OE mice, indicating that the removal of the intrinsic Ca2+ action potentials prior to the second postnatal week has no effect on the mechanoelectrical transduction apparatus. At least 3 mice for each genotype were used.",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "The 100 stiff ALDH+ or soft ALDH- 4T1 cells were injected into the mammary fat pads of NSG mice. Eight weeks later, the lung sections were H&E stained. metastasis index was calculated (D). Scale bar, 0.5 mm. n = 5 mice with metastatic tumor. Data information: two-tailed Paired Student's t test data represent mean ± SD.",
    "ncbi_link": "ALDH: 11668"
  },
  {
    "caption": "(A) The expression of BCL9L or β-catenin in stiff or soft 4T1, MCF-7, B16 or MP-1 cells was determined by western blot. (B) The expression of β-catenin and BCL9L from SGGFP, BCL9L-SGs-4T1, MCF-7, B16 or MP-1 cells were determined by western blot. Data information n = 3 independent experiments in (A and B).",
    "ncbi_link": "GFP: 
BCL9L: 80288"
  },
  {
    "caption": "(E, F) The 100 soft SGGFP or BCL9L-SGs- 4T1, B16 or MP-1 cells were injected into the mammary fat pads (4T1) of BALB/c mice or tail vein (B16 and MP-1) of NSG mice. The tumor formation was recorded (E). Six to eight weeks later, the lung sections were H&E stained. The metastatic micronodules in the lung were counted and the metastasis index was calculated (F). Scale bar, 0.5 mm. n = 3 (for B16-F1) or 5 (for MP-1) mice with metastatic tumor. Data information: Bonferroni test The data represent mean ± SD.",
    "ncbi_link": "GFP: 
BCL9L: 283149"
  },
  {
    "caption": "(F) Overall survival compared to the BCL9L level in breast cancer (BRCA, n = 536) or melanoma (n = 376) patients. Data information: Log-rank survival analysis (F). The data represent mean ± SD.",
    "ncbi_link": "BCL9L: 283149"
  },
  {
    "caption": "Expression pattern of Rgcc in the embryonic day 14.5 (E14.5) mouse cortex as detected by in situ hybridization. The right panels showed the expression patterns of NSC markers, including Pax6, Sox2, and Ki67, along the ventricular zone (VZ) of the E14.5 mouse cortex. Scale bar: 20 μm.",
    "ncbi_link": "Ki67: 17345
Pax6: 18508
Rgcc: 66214
Sox2: 20674"
  },
  {
    "caption": "Immunofluorescent staining of coronal sections of the E14.5 mouse cortex 1 day post IUE. ShRNA targeting Rgcc and control scramble-shRNA were nucleofected separately. Ki67 were co-stained with GFP. To quantify the ratio between NSC markers and GFP positive cells, only the cells in VZ and SVZ are taken into account. And ROIs of 800*1900 pixel were randomly picked for counting. Scale bars: 20 μm. Quantification of the relative ratio of Ki67 and GFP double positive cells versus GFP positive cells. Immunofluorescent staining of coronal sections of the E14.5 mouse cortex 1 day post IUE. Sox2 were co-stained with GFP. Scale bars: 20 μm. Quantification of the relative ratio of Sox2 and GFP double positive cells versus GFP positive cells. Immunofluorescent staining of coronal sections of the E14.5 mouse cortex 1 day post IUE. Pax6 were co-stained with GFP. Scale bars: 20 μm. Quantification of the relative ratio of Pax6 and GFP double positive cells versus GFP positive cells.",
    "ncbi_link": "Rgcc: 66214"
  },
  {
    "caption": "Immunofluorescent staining of coronal sections of the E17.5 mouse cortex 5 days post IUE. ShRNA targeting Rgcc and control scramble-shRNA were transfected separately at E12.5. All the brains were harvest at E17.5. Tbr1 were co-stained with GFP. And ROIs of 300*300 pixel were randomly picked along Tbr1 positive region for counting. Scale bars: 100 μm. Quantification of the relative ratio of Tbr1 and GFP double positive cells versus GFP positive cells. Immunofluorescent staining of coronal sections of the E17.5 mouse cortex 4 days post IUE. ShRNA targeting Rgcc and control scramble-shRNA were transfected separately at E13.5. All the brains were harvest at E17.5. Ctip2 were co-stained with GFP. And ROIs of 300*300 pixel were randomly picked along Ctip2 positive region for counting. Scale bars: 100 μm. Quantification of the relative ratio of Ctip2 and GFP double positive cells versus GFP positive cells. Immunofluorescent staining of coronal sections of the E17.5 mouse cortex 4 days post IUE. ShRNA targeting Rgcc and control scramble-shRNA were transfected separately at E13.5. All the brains were harvest at E17.5. Satb2 were co-stained with GFP. And ROIs of 300*300 pixel were randomly picked along ventricle for counting. Scale bars: 100 μm. Quantification of the relative ratio of Satb2 and GFP double positive cells versus GFP positive cells.",
    "ncbi_link": "Rgcc: 66214"
  },
  {
    "caption": "Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with SOX2. Scale bar: 200 μm Quantification of the VZ-like SOX2-positive rosette area. Each plot represented an individual rosette. H9, n=19; #6, n=24; #23, n=19 from 2 independent experiments. Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with PAX6 and Phospho-Histone 3 (PH3). Scale bar: 200 μm Quantification of the ratio of PH3 and PAX6 double positive cells versus the total number of PAX6 positive cells of each rosette. Each plot represented an individual organoid (H9, n=6; #6, n=8; #23, n=8 from 2 independent experiments). Three to five rosettes were analyzed for each organoid. Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with Ki67. Scale bar: 200 μm. Quantification of the VZ-like Ki67 positive rosette area. Each plot represented an individual rosette. H9, n=60; #6, n=54; #23, n=96 from 2 independent experiments.",
    "ncbi_link": "RGCC: 28984"
  },
  {
    "caption": "Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with TUJ1 and PAX6. Scale bar: 200 μm. Quantification of the ratio of TUJ1 area versus PAX6 area. (H9, n=15; #6, n=6; #23, n=9 from 2 independent experiment). Each plot represented an individual organoid. Three to five rosettes were analyzed for each organoid. Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with TBR1 and PAX6. Scale bar: 200 μm. Quantification of the ratio of TBR1-positive area around PAX6-positive area versus PAX6-positive area in each rosette. (H9, n=10; #6, n=10; #23, n=7 from 2 independent experiment). Each plot represented an individual organoid. Three to five rosettes were analyzed for each organoid. Immunofluorescent staining were performed on sections of day 45 wildtype H9 and RGCC-KO hCOs. Sections were stained with CTIP2 and PAX6. Scale bar: 200 μm. Quantification of the ratio of CTIP2 area versus PAX6 area. (H9, n=8; #6, n=8; #23, n=8 from 2 independent experiment). Each plot represented an individual organoid. Three to five rosettes were analyzed for each organoid.",
    "ncbi_link": "RGCC: 28984"
  },
  {
    "caption": "Immunofluorescent staining of coronal sections of the E14.5 mouse cortex one-day post IUE. ShRNA targeting Rgcc and control scramble-shRNA were nucleofected separately. PH3 were co-stained with GFP. The punctuated PH3 cells were at G2-phase, while PH3 cells with continuous pattern were at M-phase. To quantify the ratio between PH3 and GFP double positive cells and GFP cells, only the cells in VZ and SVZ are taken into account. Scale bar: 20 μm. n≥3 mouse brains for each group. Data are presented as mean ± SEM; n≥3 mouse brains for each group; Statistical significance was tested by Student's t-test. **, p<0.01; ***, p<0.001;",
    "ncbi_link": "Rgcc: 66214"
  },
  {
    "caption": "The Western blots results. Proteins were collected from WT hCOs and RGCC KO hCOs #6 at day 45. B-ACTIN were used as references.",
    "ncbi_link": "RGCC: 28984"
  },
  {
    "caption": "PCNT was co-stained with β -TUBULIN on WT NSCs and RGCC KO NSCs differentiated by 2D cultured dual-SMAD inhibition method. Scale bar: 5μm.",
    "ncbi_link": "RGCC: 28984"
  },
  {
    "caption": "Western blot analysis showing the depletion of PEX1 and PEX14 and the normal processing of Shh protein in the PEX1−/− and PEX14−/− hTERT-RPE1 cell clones. GAPDH served as a loading control.",
    "ncbi_link": "PEX1: 5189
PEX14: 5195"
  },
  {
    "caption": "Immunostaining with anti-PEX1 (red) or PEX14 (red), anti-PMP70 (green), anti-ninein (blue), and anti-acetylated tubulin (white) in wild-type, PEX1−/−, and PEX14−/− hTERT-RPE1 cells in quiescent G0 phase. Arrowheads indicate primary cilia. Scale bar, 10 μm. Quantification of the number of PMP70-positive peroxisomes per cell from (B). Peroxisome formation in PEX1−/− and PEX14−/− hTERT-RPE1 cells was significantly impaired compared with that of the parental cells (mean ± s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 20-25 cells per experiment). Quantification of proportion of ciliated cells from (B). Ciliogenesis in PEX1−/− and PEX14−/− hTERT-RPE1 cells was not significantly altered compared with that of the parental cells (mean ± s.d.: one-way ANOVA with Tukey's HSD, n=3: 190-200 cells per experiment).",
    "ncbi_link": "PEX1: 5189
PEX14: 5195"
  },
  {
    "caption": "Quiescent G0-phase wild-type, PEX1−/−, and PEX14−/− hTERT-RPE1 cells transfected with AcGFP1-tagged D4 as a cholesterol probe were immunostained with anti-pericentrin (white) and anti-acetylated tubulin (blue) antibodies. Cholesterol was stained with Filipin III (red). Arrows and arrowheads indicate primary cilia and cytosolic accumulations of AcGFP1-tagged D4, respectively. Scale bar, 5 μm. Quantification of the Filipin III intensity at primary cilia from (E). PEX1−/− and PEX14−/− hTERT-RPE1 cells had significant reductions in the ciliary signal of Filipin III (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively. Quantification of the AcGFP1-tagged D4 intensity at primary cilia from (E). The ciliary signal of AcGFP1-tagged D4 in PEX1−/− and PEX14−/− hTERT-RPE1 cells was significantly diminished (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 25-30 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "GFP1: 
PEX1: 5189
PEX14: 5195"
  },
  {
    "caption": "Quiescent G0-phase wild-type, PEX1−/−, and PEX14−/− hTERT-RPE1 cells were treated with or without 1.5% methyl-β-cyclodextrin for 45 min, and then incubated with or without cholesterol (cholesterol/methyl-β-cyclodextrin complex) for 1 h. After removing exogenous cholesterol, they were stimulated with 50 nM Shh-N for 24 h in the presence of pravastatin, and then immunostained with anti-Smo (green), anti-acetylated-tubulin (blue), and anti-γ-tubulin (red) antibodies. For the alternative cholesterol complementation, LDL (0.06 mg/ml) was co-incubated with Shh-N and pravastatin for 24 h after methyl-β-cyclodextrin-mediated cholesterol depletion. Scale bar, 2.5 μm. Quantification of the Smo intensity at primary cilia in wild-type, PEX1−/−, and PEX14−/− hTERT-RPE1 cells from (H). PEX1−/− and PEX14−/− hTERT-RPE1 cells exhibited the dampened Shh-N ligand-induced ciliary accumulation of Smo. The complementation of exogenous cholesterol (cholesterol/methyl-β-cyclodextrin complex) restored the ciliary accumulation of Smo in both PEX-knockout cells, while the LDL complementation did not rescue the ciliary phenotypes efficiently (*p<0.05, **p<0.01, ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 90-100 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "PEX1: 5189
PEX14: 5195
PEX: 5195///5189"
  },
  {
    "caption": "hTERT-RPE1 cells were transfected with AcGFP1-tagged EHD3 and cultured without serum for 24 h before immunostaining with anti-GFP (green), anti-ARL13B (blue), anti-PMP70 (white), and anti-phospho-S473-Akt (red) antibodies. The scale bars represent 2.5 μm.",
    "ncbi_link": "GFP1: 
EHD3: 30845"
  },
  {
    "caption": "3×FLAG-tagged EHD1 or EHD3 and AcGFP1-tagged PEX14 were coexpressed in HEK293T cells and then immunoprecipitated from whole-cell lysates using the anti-FLAG antibody. AcGFP1-tagged PEX14 and 3×FLAG-tagged EHD1 or EHD3 fragments in the IP fractions and inputs were detected by western blotting.",
    "ncbi_link": "FLAG: 
GFP1: 
EHD1: 10938
EHD3: 30845
PEX14: 5195"
  },
  {
    "caption": "3D reconstitution of the quiescent G0-phase hTERT-RPE1 cells transfected with AcGFP1-tagged EHD3 (white) immunostained with anti-acetylated-tubulin (blue) and anti-PEX14 (red) antibodies. Cholesterol was stained with Filipin III (green). Cholesterol-containing peroxisome interacted with the ciliary pocket (arrow). The scale bars indicate 2 μm.",
    "ncbi_link": "GFP1: 
EHD3: 30845"
  },
  {
    "caption": "Maximum projection of z-stack sections of hTERT-RPE1 cells expressing MCHR1-GFP (blue), DsRed2-PACT (red) and ECFP-SKL (green) 48 h after serum starvation. The ECFP-SKL-positive cell with primary cilia, indicated by the red box, was analyzed by FIB-SEM. Top, differential interference contrast (DIC); bottom, merged image. Scale bar, 10 µm.",
    "ncbi_link": "DsRed2: 
ECFP: 
GFP: 
SKL: 
MCHR1: 83567
PACT: 8575"
  },
  {
    "caption": "Western blot analysis showing depletion of ORP3 in the ORP3−/− hTERT-RPE1 cell clones. GAPDH served as a loading control.",
    "ncbi_link": "ORP3: 26031"
  },
  {
    "caption": "ORP3+/+ and ORP3−/− hTERT-RPE1 cells incubated for 24 h without serum were immunostained with anti-pericentrin (red) and anti-acetylated tubulin (blue) antibodies. Cholesterol was stained with Filipin III (green). Arrows indicate primary cilia. Scale bar, 5 μm. Quantification of the Filipin III intensity at primary cilia from (C). ORP3−/− hTERT-RPE1 cells exhibited a significant reduction of ciliary cholesterol (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "ORP3: 26031"
  },
  {
    "caption": "Three-dimensional reconstitution of the quiescent G0-phase ORP3+/+ and ORP3−/− hTERT-RPE1 cells immunostained with anti-ARL13B (blue), anti-phospho-S473-Akt (red), anti-ORP3 (green), and anti-PMP70 (white) antibodies indicates that ORP3 at the ciliary pocket (arrow and arrowhead) mediates the membrane regions of ciliary pocket and peroxisomes (arrowhead). The scale bars indicate 5 μm. Quantification of proportion of primary cilia interacting with peroxisomes from (E). Depletion of ORP3 significantly interfered with the spatial interaction between peroxisomes and primary cilia (mean ± s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 45-50 cells per experiment).",
    "ncbi_link": "ORP3: 26031"
  },
  {
    "caption": "3×FLAG-tagged ORP3 and AcGFP1-tagged PEX14, EHD1 or EHD3 were coexpressed in HEK293T cells and then immunoprecipitated from whole-cell lysates using the anti-FLAG antibody. 3×FLAG-tagged ORP3 and AcGFP1-tagged PEX14, EHD1 or EHD3 fragments in the IP fractions and inputs were detected by western blotting.",
    "ncbi_link": "FLAG: 
GFP1: 
EHD1: 10938
EHD3: 30845
ORP3: 26031
PEX14: 5195"
  },
  {
    "caption": "ORP3−/− hTERT-RPE1 cells were transfected with AcGFP1-tagged ORP3, PH domain deleted-ORP3 mutant (ΔPH), FFAT motif-deleted-ORP3 mutant (ΔFFAT), or OHD domain deleted-ORP3 mutant (ΔOHD) and cultured without serum for 24 h before Filipin-III (green)-mediated cholesterol staining and immunostaining with anti-GFP (red), anti-pericentrin (white), and anti-acetylated-tubulin (blue) antibodies. Arrows represent AcGFP1-tagged ORP3 or the mutants localized to the ciliary pocket. AcGFP1-tagged ORP3ΔPH mutant mis-localized to the ciliary pocket. The scale bars indicate 5 μm. Quantification of the Filipin III intensity at primary cilia from (H). AcGFP1-tagged ORP3 deletion mutants did not restore the ciliary cholesterol insufficiency in the ORP3−/− hTERT-RPE1 cells (*p<0.05, ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "GFP1: 
ORP3: 26031"
  },
  {
    "caption": "Rabin8+/+ and Rabin8−/− hTERT-RPE1 cells incubated for 24 h without serum were immunostained with anti-pericentrin (red) and anti-acetylated tubulin (blue) antibodies. Cholesterol was stained with Filipin III (green). Scale bar, 5 μm. Quantification of the Filipin III intensity at primary cilia from (A). Rabin8−/− hTERT-RPE1 cells exhibited a significant reduction of ciliary cholesterol (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "Rabin8: 117177"
  },
  {
    "caption": "Quiescent G0-phase Rabin8+/+ and Rabin8−/− hTERT-RPE1 cells were immunostained with anti-ARL13B (blue), anti-phospho-S473-Akt (red), anti-ninein (green), and anti-PMP70 (white) antibodies. Arrow indicates the peroxisomes contacting the ciliary pocket. Scale bar, 5 μm. Quantification of (C) indicating that disruption of the Rabin8 gene significantly inhibited the spatial interaction between peroxisomes and primary cilia (mean ± s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 45-50 cells per experiment).",
    "ncbi_link": "Rabin8: 117177"
  },
  {
    "caption": "Quiescent G0-phase hTERT-RPE1 cells transiently expressing PEX3-GFP-FRB (green) and tdTomato-BicD2-FKBP (red) treated with rapamycin were imaged live for 10 min by confocal microscopy (Movie EV10). Scale bar, 5 μm.",
    "ncbi_link": "GFP: 
tdTomato: 
BicD2: 76895
FKBP: 2280
PEX3: 8504"
  },
  {
    "caption": "Quiescent G0-phase Rabin8+/+ and Rabin8−/− hTERT-RPE1 cells transfected with PEX3-GFP-FRB (red) and tdTomato-BicD2-FKBP (white) were treated with or without 100 μM rapamycin for 30 min, and then immunostained with anti-acetylated-tubulin (blue) antibody. Cholesterol was stained with Filipin III (Green). Arrows indicate the enrichment of ciliary cholesterol. The scale bars represent 5 μm. Quantification of the Filipin III intensity at primary cilia from (G). Rapamycin-induced peroxisome targeting to the ciliary pocket restored the reduction of ciliary cholesterol in the Rabin8−/− hTERT-RPE1 cells (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "GFP: 
tdTomato: 
BicD2: 76895
FKBP: 2280
PEX3: 8504
Rabin8: 117177"
  },
  {
    "caption": "Rabin8−/− hTERT-RPE1 cells were transfected with AcGFP1-tagged Rabin8, GFP-tagged Rab8A, GFP-tagged Rab8A-Q67L (constitutively active form), GFP-Rab8B, GFP-Rab8B-Q67L (constitutively active form), AcGFP1-tagged Rab10, or AcGFP1-tagged Rab10-Q68L (constitutively active form), and then immunostained with anti-GFP (red), anti-acetylated-tubulin (blue), and anti-ninein (white) antibodies. Cholesterol was stained with Filipin III (Green). Arrows indicate the enrichment of ciliary cholesterol. The scale bars represent 5 μm. Quantification of (I) showing that AcGFP1-tagged Rabin8 and AcGFP1-tagged Rab10-Q68L effectively restored the defect in ciliary enrichment of cholesterol in Rabin8−/− hTERT-RPE1 cells (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 35-40 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "GFP: 
GFP1: 
Rab10: 10890
Rabin8: 117177
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "Whole-cell lysates from HEK293T cells expressing AcGFP1 or AcGFP1-tagged PEX14 and 3×FLAG-tagged KIFC3 were immunoprecipitated with anti-FLAG antibody and immunoblotted with anti-GFP or anti-FLAG antibody.",
    "ncbi_link": "FLAG: 
GFP1: 
KIFC3: 3801
PEX14: 5195"
  },
  {
    "caption": "Whole-cell lysates from HEK293T cells expressing AcGFP1-tagged KIFC3 and 3×FLAG-tagged Rab10 or Rab10-Q68L were immunoprecipitated with anti-FLAG antibody and immunoblotted with anti-GFP or anti-FLAG antibody.",
    "ncbi_link": "FLAG: 
GFP1: 
KIFC3: 3801
Rab10: 10890"
  },
  {
    "caption": "Whole-cell lysates from HEK293T cells expressing AcGFP1-tagged Pex14 and 3×FLAG-tagged Rab10 or Rab10-Q68L were immunoprecipitated with anti-FLAG antibody and immunoblotted with anti-GFP or anti-FLAG antibody.",
    "ncbi_link": "FLAG: 
GFP1: 
Pex14: 5195
Rab10: 10890"
  },
  {
    "caption": "Western blot analysis of the ciliary cholesterol trafficking-associated components in Pex1+/+ and Pex1−/− hTERT-RPE1 cells. Total cell lysates were separated to crude peroxisomal (Crude Pex), lysosomal and mitochondrial (Lyso/Mito), and peroxisomal (PEX) fractions. CYPOR, a lysosomal and mitochondrial protein, served as a positive control for the Lyso/Mito fractionation. Total cell lysates were gradually injected at 20 µg and 5 µg into a gel for SDS-PAGE, while equal amounts (5 µg) of protein from each fraction were loaded. Rabin8, Rab10, and KIFC3 were concentrated in the PEX fraction in Pex1+/+ hTERT-RPE1 cells. CYPOR (cytochrome P450 reductase) is a mitochondrial protein.",
    "ncbi_link": "Pex1: 5189"
  },
  {
    "caption": "Quiescent G0-phase hTERT-RPE1 cells transfected with 3×FLAG-tagged KIFC3 were immunostained with anti-FLAG (green), anti-PEX14 (red), and anti-α-tubulin (white) antibodies. Magnified 3D-constituted images of the boxed regions showing peroxisomes are located on the microtubule arrays via KIFC3 (arrows). The scale bars indicate 5 μm.",
    "ncbi_link": "FLAG: 
KIFC3: 3801"
  },
  {
    "caption": "Western blot analysis showing depletion of KIFC3 in the KIFC3−/− hTERT-RPE1 cell clones. GAPDH served as a loading control.",
    "ncbi_link": "KIFC3: 3801"
  },
  {
    "caption": "KIFC3+/+ and KIFC3−/− hTERT-RPE1 cells incubated for 24 h without serum were immunostained with anti-pericentrin (red) and anti-acetylated tubulin (blue) antibodies. Cholesterol was stained with Filipin III (green). Scale bar, 5 μm. Quantification of (G) indicating that KIFC3−/− hTERT-RPE1 cells significantly reduced the ciliary accumulation of cholesterol (***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "KIFC3: 3801"
  },
  {
    "caption": "Quiescent G0-phase KIFC3+/+ and KIFC3−/− hTERT-RPE1 cells were immunostained with anti-ARL13B (blue), anti-phospho-S473-Akt (red), anti-ninein (green), and anti-PMP70 (white) antibodies. Arrows represent the peroxisomes contacting the ciliary pocket. Scale bar, 5 μm. Quantification of (I) showing that disruption of the KIFC3 gene significantly interfered with the contact between peroxisomes and primary cilia (mean ± s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 45-50 cells per experiment).",
    "ncbi_link": "KIFC3: 3801"
  },
  {
    "caption": "KIFC3−/− hTERT-RPE1 cells were transfected with AcGFP1, AcGFP1-tagged KIFC3, rod domain-deleted KIFC3 mutant (ΔRod), or motor domain-deleted KIFC3 mutant (ΔMotor) and cultured without serum for 24 h before Filipin-III (green)-mediated cholesterol staining and immunostaining with anti-GFP (red), anti-pericentrin (white), and anti-acetylated-tubulin (blue) antibodies. Arrows represent ciliary localization of cholesterol. The scale bars indicate 5 μm. Quantification of the Filipin III intensity at primary cilia from (K). AcGFP1-tagged KIFC3 deletion mutants did not restore the ciliary cholesterol insufficiency in the KIFC3−/− hTERT-RPE1 cells (mean +/- s.d.: ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 40-50 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "GFP1: 
KIFC3: 3801"
  },
  {
    "caption": "Quiescent G0-phase wild-type, Rab10−/−, KIFC3−/−, ORP3−/−, and EHD3−/− hTERT-RPE1 cells transfected with PEX3-GFP-FRB (red) and tdTomato-BicD2-FKBP (white) were treated with or without 100 μM rapamycin for 30 min, and then immunostained with anti-acetylated-tubulin (blue) antibody. Cholesterol was stained with Filipin III (Green). Arrows indicate the enrichment of ciliary cholesterol. The scale bars represent 5 μm.",
    "ncbi_link": "GFP: 
tdTomato: 
BicD2: 76895
EHD3: 30845
FKBP: 2280
KIFC3: 3801
ORP3: 26031
PEX3: 8504
Rab10: 10890"
  },
  {
    "caption": "Quantification of the Filipin III intensity at primary cilia from (A). Rapamycin-induced peroxisome targeting to the ciliary pocket restored the insufficiency of ciliary cholesterol in the Rab10−/−and KIFC3−/−hTERT-RPE1 cells, but not in ORP3−/−and EHD3−/− hTERT-RPE1 cells (*p<0.05, **p<0.01, ***p<0.001: one-way ANOVA with Tukey's HSD, n=3: 35-40 cells per experiment). In the boxplot, medians, 25th/75th percentile and min/max were represented by the central lines, the box limits, and the whiskers/error bars, representatively.",
    "ncbi_link": "EHD3: 30845
KIFC3: 3801
ORP3: 26031
Rab10: 10890"
  },
  {
    "caption": "(A) PolyP accumulation in vivo. The polyP content of wild-type cells was set to 100%. Knockout of Vtc1, Vtc2, Vtc3 or Vtc4 impacts cellular polyP levels. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "Vtc1: 856803
Vtc2: 850544
Vtc3: 856088
Vtc4: 853441"
  },
  {
    "caption": "Cellular polyP content of Vtc4p point mutants expressed under the control of their native promoters in the vtc4Δ background. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "vtc4: 853441
Vtc4: 853441"
  },
  {
    "caption": "Cellular polyP content of VTC4 and VTC3 point mutants expressed under the control of their native promoters in the vtc4Δ and vtc3Δ(vtc2Δ) backgrounds, respectively. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "vtc2: 850544
VTC3: 856088
vtc3: 856088
VTC4: 853441
vtc4: 853441"
  },
  {
    "caption": "Cellular polyP content of VTC4 point mutants expressed under the control of their native promoters in the vtc4Δ backgrounds. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "VTC4: 853441
vtc4: 853441"
  },
  {
    "caption": "PolyP synthesis by isolated vacuoles carrying Vtc4(ΔSPX)/Vtc3/Vtc1 complex, Vtc4/Vtc3(ΔSPX)/Vtc1 complex or Vtc4/Vtc3/Vtc1 complex in the absence or presence of 1 μM 5-InsP7 or 1,5-InsP8 in vitro. The reaction system is detailed in Methods. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "Vtc1: 856803
Vtc3: 856088
Vtc4: 853441"
  },
  {
    "caption": "PolyP synthesis by isolated vacuoles carrying Vtc4/Vtc3(R223E)/Vtc1 complex, Vtc4/Vtc3(R226E)/Vtc1 complex or Vtc4/Vtc3/Vtc1 complex in the absence or presence of 1 μM 5-InsP7 or 1,5-InsP8 in vitro. The reaction system is detailed in Methods. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "Vtc1: 856803
Vtc3: 856088
Vtc4: 853441"
  },
  {
    "caption": "Cellular polyP content of VTC4, VTC3 and VTC1 point mutants expressed under the control of their native promoters in the vtc4Δ, vtc3Δ(vtc2Δ) and vtc1Δ backgrounds, respectively. Δ indicates that the entire subunit was knocked out. FL indicates full length, indicating that the subunit has not been modified in any way. Data show the mean±s.d (biological replicates n=3).",
    "ncbi_link": "VTC1: 856803
vtc1: 856803
vtc2: 850544
VTC3: 856088
vtc3: 856088
VTC4: 853441
vtc4: 853441"
  },
  {
    "caption": "(F) NO donors increased EGFP-HDQ74 aggregates in a dose-dependent manner in EGFP-HDQ74-transfected Atg5+/+, but not in Atg5−/−, MEFs. Atg5−/− MEFs had more EGFP-HDQ74 aggregates than Atg5+/+ MEFs.",
    "ncbi_link": "Atg5: 11793
HD: 15194"
  },
  {
    "caption": "(D and E) Immunoprecipitation with anti-Flag M2 affinity agarose gel and immunoblotting with anti-Myc antibody shows that NO donors increased the interaction of Flag-Beclin 1 with WT Myc-Bcl-2 (D), but not with AAA Myc-Bcl-2 (E), in HeLa cells transfected with WT Myc-Bcl-2 (D) or AAA Myc-Bcl-2 (E) along with either empty Flag or Flag-Beclin 1. Asterisk denotes IgG band (E).",
    "ncbi_link": "Bcl-2: 596
Beclin 1: 8678"
  },
  {
    "caption": "(F) Immunoprecipitation with anti-Flag M2 affinity agarose gel and immunoblotting with anti-Vps34 antibody shows that NO donors decreased Flag-Beclin 1-hVps34 interaction in HeLa cells transfected with hVps34 along with either empty Flag or Flag-Beclin 1.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(G) Immunoprecipitation with anti-Flag M2 affinity agarose gel and immunoblotting with anti-Vps34 antibody shows that AAA Myc-Bcl-2 decreased Flag-Beclin 1-hVps34 interaction in the presence (right panel) or absence (left panel) of DETA NONOate in HeLa cells transfected with hVps34 along with either empty Flag or Flag-Beclin 1, and with pcDNA3.1 or AAA Myc-Bcl-2. Graphical data denote mean ± SEM.",
    "ncbi_link": "Bcl-2: 596
Beclin 1: 8678"
  },
  {
    "caption": "(A) Immunoblot analysis with anti-LC3 antibody shows that DETA NONOate reduced autophagosome synthesis in bafilomycin A1-treated WT Bcl-2 and AAA Bcl-2 MEFs.",
    "ncbi_link": "Bcl-2: 596"
  },
  {
    "caption": "(B and C) NO donors decreased EGFP-LC3 vesicles in EGFP-LC3-transfected WT Bcl-2 and AAA Bcl-2 MEFs (C). Images were acquired by a confocal microscope (B). WT Bcl-2 and AAA Bcl-2 MEFs were analyzed separately.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(D) NO donors increased EGFP-HDQ74 aggregates in EGFP-HDQ74-transfected WT Bcl-2 and AAA Bcl-2 MEFs. WT Bcl-2 and AAA Bcl-2 MEFs were analyzed separately.",
    "ncbi_link": "Bcl-2: 12043
HD: 15194"
  },
  {
    "caption": "(E) Immunoblot analysis with anti-LC3 antibody shows that DETA NONOate reduced autophagosome synthesis in bafilomycin A1-treated WT Jnk, Jnk1−/−, and Jnk2−/− MEFs.",
    "ncbi_link": "Jnk1: 26419
Jnk2: 26420"
  },
  {
    "caption": "(H) Immunoblot analyses with anti-phospho-S6K and anti-phospho-S6 antibodies show that NO donors activated mTORC1 in WT Bcl-2 and AAA Bcl-2 MEFs.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(A) Immunoblot analyses with anti-phospho-S6K and anti-phospho-S6 antibodies show that NO donors activated mTORC1 in Tsc2+/+ MEFs, but not in Tsc2−/−, MEFs.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "(C) Immunoblot analyses with anti-phospho-S6K and anti-phospho-S6 antibodies show that NO donors activated mTORC1 in Ikkβ+/+ MEFs, but not in Ikkβ−/− MEFs.",
    "ncbi_link": "Ikkβ: 16150"
  },
  {
    "caption": "(D) Immunoblot analysis with anti-LC3 antibody shows that DETA NONOate reduced autophagosome synthesis in bafilomycin A1-treated Tsc2+/+ and Tsc2−/− MEFs.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "(E) DETA NONOate decreased EGFP-LC3 vesicles in Tsc2+/+ and Tsc2−/−MEFs transfected with EGFP-LC3, along with either pcDNA3.1 or AAA Myc-Bcl-2. Although it further reduced EGFP-LC3 vesicles in Tsc2+/+MEFs expressing AAA Myc-Bcl-2 compared to mock-transfected Tsc2+/+MEFs, this effect was not seen in Tsc2−/−MEFs. Tsc2+/+ and Tsc2−/−MEFs were analyzed separately. Graphical data denote mean ± SEM.",
    "ncbi_link": "Bcl-2: 12043
Tsc2: 22084"
  },
  {
    "caption": "(A-D) Immunoblot analyses with anti-LC3, along with anti-nNOS, anti-iNOS, and anti-eNOS antibodies, show decreased LC3-II levels in stable HEK293 cell lines overexpressing nNOS (A and D), iNOS-GFP (B and D), or eNOS (C and D) compared to HEK293 control cells in the presence or absence of bafilomycin A1.",
    "ncbi_link": "nNOS: 4842
iNOS: 4843
eNOS: 4846"
  },
  {
    "caption": "(A-F) Immunoblot analyses with anti-nNOS, anti-iNOS, anti-eNOS, anti-phospho-JNK1, anti-phospho-Bcl-2, anti-phospho-S6K, and anti-phospho-S6 antibodies show that stable HEK293 cell lines overexpressing nNOS (A and D), iNOS-GFP (B and E), or eNOS (C and F) inhibited both the JNK1-Bcl-2 and mTORC1 pathways compared to the HEK293 control cells under basal (FM) (A-C) or starvation (HBSS) (D-F) conditions. Graphical data denote mean ± SEM.",
    "ncbi_link": "nNOS: 4842
iNOS: 4843
eNOS: 4846"
  },
  {
    "caption": "(D) L-NAME reduced EGFP-HDQ74 aggregates in EGFP-HDQ74-transfected Atg5+/+, but not in Atg5−/−, MEFs.",
    "ncbi_link": "Atg5: 11793
HD: 15194"
  },
  {
    "caption": "(E) Drosophila expressing mutant huntingtin exon 1 (Q120) shows a significant decrease in neurodegeneration (p < 0.001, paired t test) upon L-NAME treatment compared to DMSO.",
    "ncbi_link": "huntingtin: 43392"
  },
  {
    "caption": "(F) Expression of an endogenous negative regulator of NOS activity (NOS4) significantly attenuates neurodegeneration (p < 0.05, paired t test) in Drosophila expressing mutant huntingtin exon 1 (Q120).",
    "ncbi_link": "NOS4: 
huntingtin: 43392"
  },
  {
    "caption": "(G-I) Images from the retina of transgenic HD zebrafish show mutant huntingtin aggregates (arrows) (G). Treatment with rapamycin or L-NAME reduced the number of aggregates (H). L-NAME did not reduce aggregates in the presence of NH4Cl, which increased aggregate count (I).",
    "ncbi_link": "huntingtin: 30214"
  },
  {
    "caption": "Time lapse images of T6SS activity in tagged parental strain (VipA-mCherry2) and ∆tssA mutant background. The parental strain forms multiple dynamic structures per cell. ∆tssA mutant predominantly forms dynamic sheath spots (white arrow) and few WT-like sheath structures (blue arrow). Scale bars: 2 µm.",
    "ncbi_link": "tssA: 2612844"
  },
  {
    "caption": "H2-T6SS dynamics in tagged parental strain (∆retS TssB2-mCherry2, referred to as WT H2) and ΔtssA2PA strain. Blue arrow indicates extending and contracting T6SS sheath structures, white arrow points to dynamic sheath spots. The WT H2 strain harbors multiple dynamic sheath structures per cell, while the ΔtssA2PA strain displays very few dynamic spots or extended and contracting structures. Scale bars: 2 µm.",
    "ncbi_link": "retS: 877881
tssA: 2612844"
  },
  {
    "caption": "Fluorescence microscopy of T6SS dynamics in a double tagged strain (∆retS TssB2-mCherry2 TssA2PA-mNeonGreen). White arrow indicates full cycle of extending and contracting T6SS sheath. Scale bar: 1 µm.",
    "ncbi_link": "retS: 877881"
  },
  {
    "caption": "The ∆tagA mutant displays long and bent but still dynamic structures. Scale bar: 2 µm. Frames from time lapse movies showing sheath dynamics in the ∆tagA mutant. Sheath polymerization does not stop when the distal end reaches opposing membrane (white arrow). Continued polymerization causes the sheath to tilt and distal end to move towards the bacterial cell pole, ultimately effecting bending of the whole structure. C. Sheath detaches from its membrane anchor (orange arrow), keeps extending to maximum cell length and then contracts. Scale bars: 1 µm.",
    "ncbi_link": "tagA: 2612830"
  },
  {
    "caption": "H1-T6SS dynamics in tagged parental strain (∆retS TssB1-mCherry2, referred to as WT H1) and ΔtssA1PA strain. Blue arrow indicates extending and contracting T6SS sheath structures, white arrow points to dynamic sheath spots. Scale bars: 2 µm.",
    "ncbi_link": "retS: 877881
tssA: 2612844"
  },
  {
    "caption": "Fluorescence microscopy of T6SS dynamics in ∆retS TssB1-mCherry2 strain harboring pPSV35 plasmid with TssA1PA-mNeonGreen fusion. Scale bar: 2 µm.",
    "ncbi_link": "retS: 877881"
  },
  {
    "caption": "(B) Detection of  S-acylation  of BSKs in plant cells. 12 BSK proteins were fused with GFP  at their C terminus and expressed in Arabidopsis protoplasts  for 24 hours and the cells were collected for Biotin-switch assay. Cell lysates are shown as input, and the  S-acylated proteins enriched on the resin which is dependent on hydroxylamine  (NH2OH) are indicated as pulldown  samples. All images of anti-GFP immunoblots  are representative of three biological independent experiments.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(D) Effect of  2-BP on subcellular localization  of BSK1  in  root cells of intact transgenic plants. Six-day-old seedlings of 35S:BSK1-GFP  were treated with 80 μM 2-BP for 2 h; DMSO  was supplemented in the control samples. Representative GFP  (green) and merged (with bright field) signals from three biologically independent experiments are shown. Bars, 10 µm.",
    "ncbi_link": "GFP: 
BSK1: 829676"
  },
  {
    "caption": "(A, B) Identification of  S-acylation sites on BSK1  and BSK3. The wild-type (WT) and indicated mutant versions of BSK1-GFP  (A) and BSK3-GFP  (B) were expressed in protoplasts  for biotin-switch assay. Images of anti-GFP immunoblots  are representative of three biological independent experiments.",
    "ncbi_link": "GFP: 
BSK1: 829676
BSK3: 828025"
  },
  {
    "caption": "(E, F) Effect of S-acylation site mutation on the localization  of BSK1  and BSK3  in intact root cells. Six-day-old seedlings  of the WT or S-acylation site mutant versions of 35S:BSK1-GFP  (E) and 35S:BSK3-GFP  (F) were subjected to localization  analysis using confocal microscopy. Representative GFP  (green) and merged (with bright field) signals in root cells  from three biologically independent experiments are shown. Bars, 10 µm.",
    "ncbi_link": "GFP: 
BSK1: 829676
BSK3: 828025"
  },
  {
    "caption": "(G, H) The effect of S-acylation site mutations on the localization  of BSK1  and BSK3  in a cell fractionation assay. The WT and mutant versions of BSK1-GFP  (G) and BSK3-GFP  (H) were expressed in protoplasts  and the total proteins (T) were divided into soluble  (S) and pellet  (P) fractions using ultra-centrifugation. Representative immunoblotting  data using an anti-GFP  antibody are shown.",
    "ncbi_link": "GFP: 
BSK1: 829676
BSK3: 828025"
  },
  {
    "caption": "(B) Co-IP  result for measuring the function of BSK1 S-acylation in its interaction  with BRI1. Free GFP  (negative control) or the WT/C3S version of BSK1-GFP  was co-expressed with BRI1-MYC  in plant cells for co-IP using an anti-GFP  resin. The proteins in the input and IP  samples were detected via immunoblots  with anti-MYC  or anti-GFP  antibodies.",
    "ncbi_link": "GFP: 
MYC: 
BRI1: 830095
BSK1: 829676"
  },
  {
    "caption": "(E, F) The effect of S-acylation on the function of BSK3   in BR responses. The WT or 3M (C5, 10, 11S) version of BSK3  driven by a native promoter was introduced into the bsk3-1 mutant to generate complementation lines. The phenotype of 8-day-old seedlings  with and without 100 nM of BL  treatment is shown in (E). Bars, 1 cm. Quantitative data of hypocotyl  and root  length under the control or BL  treatment condition are shown in (F). Data are means ± SD from 20 seedlings  in four independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "BSK3: 828025
bsk3: 828025"
  },
  {
    "caption": "(C) Detection of the regulation of BSK1 S-acylation mediated by SA. BSK1-GFP  was expressed in protoplasts  with 0-, 20-, 40-, or 60-min treatment with 100 µM of SA. Cells were collected for S-acylation  detection in a biotin-switch assay. Representative immunoblots  are shown in the top graph. Immunoblot  signals were quantified by ImageJ and the  S-acylation levels were calculated from relative signals ([pulldown+/input+] - [pulldown-/ input-]). The relative S-acylation level of the 0 min sample was set to 1. The data in the bottom graph are means ± SD from three biologically independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "GFP: 
BSK1: 829676"
  },
  {
    "caption": "(D, E) Effect of SA  on the physiological function of BSK1. The indicated seeds  were germinated on the MS medium with or without 40 µM of SA. The photographs were taken 8 days after germination. Representative images are shown in (D). Bars, 1 cm. Quantitative data of fresh weight  (per 10 seedlings) of different genotypes are shown in (E). Data are means ± SD from three biologically independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "BSK1: 829676"
  },
  {
    "caption": "(A) Identification of the de-S-acylation  enzyme of BSK1. BSK1-RFP  was co-overexpressed with 11 GFP-fused ABAPT members in protoplasts  respectively (free GFP  was used as a control). Cells with both RFP  and GFP  signals were used for analyzing the localization  of BSK1-RFP. The predominant localization  patterns of BSK1-RFP  are shown. The RFP  (magenta), GFP  (green), and the merged (with bright field in gray) signals are included in the top graph. Bars, 5 µm. The quantitative data of the percentages of cells with mislocalization of BSK1-GFP  (100 cells for each sample) are shown in the bottom graph. Data are means ± SD from three biologically independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "RFP: 
GFP: 
BSK1: 829676"
  },
  {
    "caption": "(B) Detection of the effect of ABAPT11  on the localization  of BSK members. 12 BSK-GFP  fusion proteins were co-overexpressed with RFP  (control) or ABAPT11-RFP in protoplasts. BSK-GFP localization  in cells with both RFP  and GFP  signals was recorded. Representative localization  patterns of BSK-GFP  with RFP  or ABAPT11-RFP  are shown in the top graph. Bars, 5 µm. Quantitative data of the percentages of cells with localization  changes of BSK-GFP  (100 cells for each sample) are shown in the bottom graph. Data are means ± SD from three biologically independent experiments. ****P < 0.0001, ***P < 0.001, *P < 0.05, n.s. (no significance) P > 0.05, Student's t-test (unpaired, two-tailed).",
    "ncbi_link": "RFP: 
GFP: 
ABAPT11: 832174"
  },
  {
    "caption": "(B) Effect of ABAPT11  overexpression on the BSK1 membrane  association in a cell fractionation assay. BSK1-GFP  was expressed in protoplasts  with or without ABAPT11  overexpression. Total proteins (T) were separated into soluble  (S) and pellet  (P) fractions using ultra-centrifugation. A representative immunoblot  using an anti-GFP  antibody is shown. The percentages of BSK1-GFP  in the soluble fraction were calculated from relative immunoblotting  signals (S/[S+P]). Data are means ± SD from three biologically independent experiments. **P < 0.01, Student's t-test (unpaired, two-tailed).",
    "ncbi_link": "GFP: 
BSK1: 829676
ABAPT11: 832174"
  },
  {
    "caption": "(C, D) Effect of ABAPT11  overexpression on S-acylation of BSK1  and BSK3. The S-acylation level of BSK1-GFP  (C) and BSK3-GFP  (D) with or without ABAPT11  overexpression in protoplasts  was detected in a biotin-switch assay. Representative immunoblotting image is shown in the top graphs. Quantification of relative  S-acylation levels was included in the bottom graphs. Immunoblotting  signals were quantified by ImageJ and the S-acylation levels were calculated from relative signals ([pulldown+/input+] - [pulldown-/ input-]). The relative S-acylation  level of the control sample was set to 1. Data are means ± SD from three biologically independent experiments. **P < 0.01, Student's t-test (unpaired, two-tailed).",
    "ncbi_link": "ABAPT11: 832174"
  },
  {
    "caption": "(A, B) Expression of ABAPT11  during SA  treatment. (A) Seven-day-old wild-type (WT) seedlings  were treated with 100 µM SA  for 0, 10, 20, 30, 40, 50, and 60 min before collection for RNA preparation and RT-qPCR to detect the transcript level of ABAPT11. (B) Transcript levels of ABAPT11  in wild-type (WT) and npr1  mutant 7-day-old seedlings  with or without 100 µM SA  for 20 min. ACTIN2  was used as an internal control. Data are means ± SD from triplicated replications in an experiment; the pattern was consistent in three biologically independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "ACTIN2: 821411
npr1: 842733
ABAPT11: 832174"
  },
  {
    "caption": "(C) Accumulation of ABAPT11  proteins in the SA  response. Seven-day-old seedlings  expressing ABAPT11-YFP  under its own promoter were treated with 100 µM SA  for 0, 20, 40, and 60 min before collection for immunoblotting  with an anti-GFP  antibody. Coomassie blue staining of total proteins was used as the loading control. Quantitative relative protein levels (YFP  / loading) from three biologically independent experiments are shown in the bottom graph. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "YFP: 
ABAPT11: 832174"
  },
  {
    "caption": "(D) The  S-acylation level of BSK1  in the ABAPT11  mutant during SA  treatment. BSK1-GFP  was expressed in WT or abapt11-1 mutant cells (with or without 100 µM SA  treatment for 40 min) for S-acylation  measurement in a biotin-switch assay. Representative immunoblots  are shown in the top graph. The immunoblotting  signals were quantified by ImageJ and the  S-acylation levels were calculated from relative signals ([pulldown+/input+] - [pulldown-/ input-]). The relative S-acylation level of the wild-type sample without SA  treatment was set to 1. Data are means ± SD from three biologically independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "GFP: 
BSK1: 829676
ABAPT11: 832174
abapt11: 832174"
  },
  {
    "caption": "(G, Confirmation of the SA-induced BSK1  translocation which is mediated by ABAPT11. BSK1-GFP  was expressed in WT or abapt11-1 mutant cells, with or without 100 µM SA  treatment for 40 min. Total proteins (T) were separated into soluble  (S) and pellet  (P) fractions using ultra-centrifugation. Representative immunoblots  using an anti-GFP  antibody are shown in (G).",
    "ncbi_link": "GFP: 
BSK1: 829676
abapt11: 832174
ABAPT11: 832174"
  },
  {
    "caption": "(A, B) Effect of BL  and SA on hypocotyl  development in ABAPT11  mutants. Seeds  were germinated on regular medium (Control), medium containing 80 nM BL, medium containing 40 µM SA, or medium containing both 80 nM BL  and 40 µM SA. Hypocotyl  length was measured 8 days after germination. Representative images from four independent experiments are shown in (A). Quantitative data of hypocotyl  lengths are shown in (B). Data are means ± SD from 20 seedlings  in four independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "ABAPT11: 832174"
  },
  {
    "caption": "D) Effect of BL  and SA  on root  development of ABAPT11  mutants. Four days after germination, seedlings  of WT, abapt11-1, and abapt11-2 were transferred onto a regular medium (Control), medium containing 15 nM BL, medium containing 20 µM SA, or medium containing both 15 nM BL  and 20 µM SA. Quantitative data of root  elongation 5 days after transferring are shown in (D). Data are means ± SD from 20 seedlings  in four independent experiments. Significance analysis using one-way ANOVA followed by Tukey's multiple comparison test is shown in different lower-case letters (P < 0.05).",
    "ncbi_link": "ABAPT11: 832174
abapt11: 832174"
  },
  {
    "caption": "Neurosphere assays were performed using mouse E14.5 primary neural progenitors transduced with a retroviral vector expressing Ttyh1",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "XTT assays were performed using mouse E14.5 primary neural progenitors transduced with a retroviral vector expressing Ttyh1",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Neurosphere assays were performed using mouse E14.5 primary neural progenitors transduced with a short hairpin RNA specific to Ttyh1 (shTtyh1)",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "XTT assays were performed using mouse E14.5 primary neural progenitors transduced with a short hairpin RNA specific to Ttyh1 (shTtyh1)",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Ttyh1-expressing cells in E15.5 embryonic brains that were intraventricularly electroporated at E13.5 were immunostained using an anti-GFP primary (reporter gene) and Alexa Fluor 488-conjugated secondary antibodies. GFP immunofluorescence (green) was merged with DAPI-counterstained images (blue). VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate. Scale bar: 100 μm. Quantification of (E)",
    "ncbi_link": "GFP: 
Ttyh1: 57776"
  },
  {
    "caption": "Double-immunolabeling of E15.5 brain sections electroporated in utero with Ttyh1-expressing plasmid at E13.5 using anti-GFP (green) and Sox2 (red) antibodies, and Alexa Fluor 488- and 555-conjugated secondary antibodies. Scale bar: 50 μm.",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Double-immunolabeling of E15.5 brain sections electroporated in utero with Ttyh1-expressing plasmid at E13.5 using anti-GFP (green) and Sox2 (red) antibodies, and Alexa Fluor 488- and 555-conjugated secondary antibodies. Scale bar: 50 μm. Quantification of (G) (n = 3).",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Immunolabeling of E14.5 brain sections electroporated in utero with shTtyh1 alone or in combination with a shTtyh1-resistant Ttyh1 (Ttyh1res) expression vector at E13.5 using anti-GFP and Alexa Fluor 488-conjugated secondary antibodies. The DAPI nuclear counterstain is shown in blue. Scale bar: 100 μm. Quantification of (I)",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Two days after E14.5 primary neural progenitor cells were transduced with retroviral vectors expressing (A) Ttyh1 mRNA expression levels of each indicated Notch target gene were measured by qPCR",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Two days after E14.5 primary neural progenitor cells were transduced with shTtyh1, mRNA expression levels of each indicated Notch target gene were measured by qPCR",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Effects of dominant negative MAML1 (dnMAML1) on Ttyh1-enhanced Notch target gene expression were tested by qPCR using E14.5 primary neural progenitors at 2 days posttransduction (n = 4).",
    "ncbi_link": "MAML1: 103806
Ttyh1: 57776"
  },
  {
    "caption": "The dnMAML1 plasmid was introduced with the Ttyh1 vector into embryonic brains at E13.5 and cell localization was analyzed at E15.5 by anti-GFP immunostaining. GFP and DAPI signals are shown in green and blue, respectively. VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate. Scale bar: 100 μm. E Quantification of GFP+ cell positions in (D) (n = 3). ",
    "ncbi_link": "MAML1: 103806
Ttyh1: 57776"
  },
  {
    "caption": "The NICD plasmid was electroporated with the Ttyh1 knockdown vector (shTtyh1) into embryonic brains at E13.5 and cell localization was analyzed at E14.5 by anti-GFP immunostaining. Scale bar: 100 μm. G Quantification of GFP+ cell positions in (F) (n = 3). ",
    "ncbi_link": "NICD: 18128
Ttyh1: 57776"
  },
  {
    "caption": "Effects of Ttyh1 expression on the generation of NICD at 2 days posttransduction of E14.5 neural progenitor cells were analyzed by Western blotting using an anti-NICD antibody. Quantification of band intensities",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Effects of Ttyh1 knockdown (C) on the generation of NICD at 2 days posttransduction of E14.5 neural progenitor cells were analyzed by Western blotting using an anti-NICD antibody. (B, D) Quantification of band intensities",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Ttyh1-transduced E14.5 neural progenitors were incubated with DAPT for 2 days, then cells were harvested and lysates were used for luciferase assay (n = 3).",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Effects of Ttyh1-knockdown on γ-secretase activity was also assessed using E14.5 neural progenitor cells",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Ttyh1-transduced E14.5 neural progenitors were incubated for 2 days in the presence or absence of DAPT, and samples were prepared for Western blotting using anti-NICD antibody",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Ttyh1-transduced E14.5 neural progenitors were incubated for 2 days in the presence or absence of DAPT, and samples were prepared for qPCR for Notch target genes (I)",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "The indicated plasmids were electroporated into E13.5 brains, and brain samples were harvested at E15.5 for anti-GFP immunolabeling. GFP and DAPI signals are shown in green and blue, respectively. Quantification of GFP+ cell localization in (J) dnPS1, dominant negative presenilin 1; VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate. Scale bar: 100 μm.",
    "ncbi_link": "presenilin 1: 
PS1: "
  },
  {
    "caption": "Effects of the ion selectivity-perturbing R371Q mutation in Ttyh1 E14.5 neural progenitor cells were transduced with retroviral vectors expressing each indicated gene, and 2 days posttransduction, cells were harvested for qPCR analyses of Notch target mRNAs (n = 3).",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "series of Ttyh1 mutants with deletions in the C-terminal cytoplasmic tail region , and (F) their effects on cell distribution assessed by intraventricular in utero electroporation at E13.5 followed by immunolabeling at E15.5 using anti-GFP antibody. Scale bar: 100 μm.",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Venus fluorescent protein-based bimolecular fluorescence complementation analysis of Ttyh1 and Rer1 interaction (green) in living COS-7 cells by fluorescence microscopy. Ttyh1 and Rer1 were tagged with N- and C-terminal fragments of the Venus fluorescent protein (VN and VC), respectively. DsRed2-ER was cotransfected to label the endoplasmic reticulum (ER, red). Scale bar: 25 μm.",
    "ncbi_link": "DsRed2: 
Rer1: 67830
Ttyh1: 57776"
  },
  {
    "caption": "Western blot analyses of endogenous Rer1 proteins were performed at 2 days posttransduction using E14.5 primary neural progenitor cells transduced with retroviral vectors expressing (D) Ttyh1 Quantification of relative band intensities",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "D-G Western blot analyses of endogenous Rer1 proteins were performed at 2 days posttransduction using E14.5 primary neural progenitor cells transduced with retroviral vectors expressing shTtyh1. Quantification of relative band intensities",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "Cell extracts from primary neural progenitor cells transduced with Ttyh1 retroviruses in the presence of DMSO vehicle or a proteasome inhibitor lactacystin (10 μM), were immunoblotted with an antibody to Rer1.",
    "ncbi_link": "Ttyh1: 57776"
  },
  {
    "caption": "HEK293T cells were transfected with Ttyh1-Myc and Rer1-HA expression plasmids, and after 24 h, cells were treated with cycloheximide (CHX) (100 μg/ml) and then harvested at the indicated time intervals. Cell lysates were analyzed by Western blotting using anti-HA antibody. (J) Quantification of band intensities in (I) (n = 3).",
    "ncbi_link": "HA: 
Myc: 
Rer1: 67830
Ttyh1: 57776"
  },
  {
    "caption": "γ-secretase-dependent luciferase activity was measured using primary neural progenitor cells transduced with Ttyh1 with or without Rer1 retroviral vectors at 2 days posttransduction (n = 3).",
    "ncbi_link": "Rer1: 67830
Ttyh1: 57776"
  },
  {
    "caption": "Effects of Rer1 expression on Ttyh1 activity in vivo were examined by in utero electroporation into E13.5 brains and subsequent GFP immunofluorescence of E15.5 brain sections. GFP and DAPI signals are shown in green and blue, respectively. (M) Distribution of GFP+ cells in each brain layer in (L) was quantified (n = 3). VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate. Scale bar: 100 μm.",
    "ncbi_link": "Rer1: 67830
Ttyh1: 57776"
  },
  {
    "caption": "M-O: Schematic describing the measurement of a cell's approach angle to the nearest point on the AER (M). Merged, immunofluorescent images of WT (top), slit3sq49 (centre) and s1pr2te273 (below) mesenchymal cells in sqet37Et background stained for EGFP (green), Gamma tubulin (red) and DAPI (blue). White lines run from the centre of nucleus to the nearest point on the AER, through the MTOC (N). Graph depicting the approach angles to AER of leading (Tier 1), following (Tier 2) and trailing (Tier 3) cells of WT, slit3sq49 and s1pr2te273 embryos (O). A minimum of 30 cells were measured for each tier of each genotype. *p<0.05; **p<0.005; ***p<0.001; ANOVA with Fisher's post-test.",
    "ncbi_link": "s1pr2: 170457
slit3: 80354"
  },
  {
    "caption": "C-E: Lateral Nomarski images of 48hpf larval fins which are WT (C) or slit3+/sq49 heterozygotes (D) and are injected with 300µM fn1a morpholino. Blisters are observed only when there is reduced Fn1a in slit3 heterozygotes (quantified in E).",
    "ncbi_link": "fn1a: 100005469
Fn1a: 100005469
slit3: 80354"
  },
  {
    "caption": "F-G: Lateral Nomarski images of 48hpf WT larval fins injected with 200µM gna13b alone (F) or with 300µM fn1a morpholino (G). H: Quantification of the proportion of larvae with fin blisters when low amounts of gna13 morpholinos (125µM each gna13a and gna13b MO combined or 200µm gna13b MO alone) are injected into WT, fn1a morphants (300µM MO), fn1a+/- heterozygotes and fn1a-/- mutants. Loss of a single or both copies of fn1a exacerbates reduced gna13 levels, as does knockdown of fn1a.",
    "ncbi_link": "fn1a: 100005469
gna13a: 326825
gna13: 326825///336333
gna13b: 336333"
  },
  {
    "caption": "CSTB gene expression analysis in hCOs, starting from day (d) 16 until d140. For every time point, at least 3 different samples were analyzed; each sample was made by a pool of 3 to 4 hCOs. Data are represented as mean ± SEM. Unpaired t-test (*P < 0.05, **P < 0.01).",
    "ncbi_link": "CSTB: 1476"
  },
  {
    "caption": "Real time qPCR results of PAX6, NEUN, NESTIN, CSTB gene expression levels in PAX6- and NEUN- FACS sorted nuclei from f-CTRL d135 hCOs. Data are represented as mean ± SEM. Statistical significance was based on T-student test (*P < 0.05, **P < 0.01). For PAX6, 10 samples were analyzed as biological replicates: 5 for Pax6+sorted Nuclei and 5 for Neun+sorted Nuclei; for NEUN, NESTIN and CSTB, 9 samples were analyzed as biological replicates: 5 for Pax6+sorted Nuclei and 4 for Neun+sorted Nuclei.",
    "ncbi_link": "CSTB: 1476
NESTIN: 10763
PAX6: 5080
NEUN: 146713"
  },
  {
    "caption": "Micrograph sections of d40 hCOs electroporated with GFP-empty vector control or GFP-CSTB and analyzed 5 dpe. Sections were then immunostained for GFP and KI67. The dashed lines represent the apical surface of the cavities/ventricles (V-like). The cortical plate like side is indicated (CP-like). Quantification of the total number of proliferating KI67+ cells/area (µm2) of V-like structures transfected with GFP-empty vector control or GFP-CSTB in (A).",
    "ncbi_link": "GFP: 
CSTB: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E16 mouse cerebral cortices electroporated at E14 with GFP-empty vector or GFP-Cstb and analyzed 2 dpe and immunostained with GFP,Ki67 and BrdU 30 minutes after BrdU injection. Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles. Quantification of the total number of proliferating Ki67+ cells/area(µm2)(D) and Ki67+Brdu+ cells/area(µm2)(E) of ventricles transfected with GFP-empty vector or GFP-Cstb in (C).",
    "ncbi_link": "GFP: 
Cstb: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E16 mouse cerebral cortices electroporated at E14 with GFP-empty vector or GFP-Cstb, analyzed 2 dpe and immunostained with GFP and Phospho-Histone H3 (PH3)(F) and with GFP, Pax6 and Tbr2 (G). Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles.",
    "ncbi_link": "GFP: 
Cstb: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E17 mouse cerebral cortices electroporated at E14 co-electroporated with mCherry expressing vector and HA-empty vector or -Cstb, and analyzed 3 dpe. Immunostaining with RFP to identify electroporated cells and GFP to identify migrating interneurons in the GAD65-GFP transgenic mouse line. Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles. Distribution of GFP+ interneurons in the 5 equal Bins of the mouse developing cortex-Bin1 corresponded to apical side and Bin5 to pial side. Ventricle (V) is indicated. The dashed lines represent the apical surface of the ventricles.",
    "ncbi_link": "GFP: 
HA: 
mCherry: 
Cstb: 25308
GAD65: 14417"
  },
  {
    "caption": "Micrograph of coronal sections of E17 mouse cerebral cortices electroporated at E14 co-electroporated with mCherry and HA-Cstb expressing vector, analyzed 3 dpe. Immunostaining with RFP to identify electroporated cells and GFP to identify migrating interneurons in the GAD67-GFP transgenic mouse line. Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles. Distribution of GFP+ interneurons in the 5 equal Bins of the mouse developing cortex comparing electroporated sides with the contralateral ones in the same section to avoid different distribution of interneurons rostro-caudally.",
    "ncbi_link": "GAD67: 
GFP: 
HA: 
mCherry: 
Cstb: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E17 mouse cerebral cortices electroporated at E14 with GFP-miR-neg vector (CTRL) and GFP-miRNA-Cstb (KD), analyzed 3 dpe and immunostained with GFP. Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles. Distribution of electroporated GFP+ cells in the mouse cortex. The cortex was subdivided in 5 equal Bins -Bin1 corresponded to apical side and Bin5 to pial side of the cortex and GFP+ cells calculated in each Bin. Nuclei (blue) are stained with DAPI.",
    "ncbi_link": "GFP: 
Cstb: 13014"
  },
  {
    "caption": "Micrograph of coronal sections of E17 mouse cerebral cortices electroporated at E14 with GFP-empty vector control and GFP-miRNA-Cstb, analyzed 3 dpe and immunostained with GFP and Ki67. Ventricle (V) is indicated. The dashed lines represent the apical surface of the ventricles. Quantification of the total number of proliferating Ki67+ cells/area (µm2) of ventricular structures transfected with GFP-miR-neg vector or GFP-miRNA- Cstb in (C). Nuclei (blue) are stained with DAPI.",
    "ncbi_link": "GFP: 
Cstb: 13014"
  },
  {
    "caption": "Micrograph sections of d40 hCOs electroporated with GFP-CSTB expressing vector or GFP-R68X mutant and analyzed 5 dpe. Sections were immunostained for GFP and Ki67. The dashed lines represent the apical surface of the cavities/ventricles (V-like). The cortical plate like side is indicated (CP-like). Quantification of the total number of proliferating KI67+ cells/area(µm2)(F)and Ki67+GFP+ cells/area(µm2)(G) of ventricles like structures transfected with GFP-empty vector control, GFP-CSTB or GFP-R68X mutant in (E).",
    "ncbi_link": "GFP: 
CSTB: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E16 mouse cerebral cortices electroporated at E14 with GFP-empty vector control, GFP-Cstb or GFP-R68X, analyzed 2 dpe and immunostained with GFP and Phospho-Histone H3 (PH3). Ventricle (V) and cortical plate (CP) are indicated. The dashed lines represent the apical surface of the ventricles. Distribution of electroporated GFP+ cells in the mouse cortex. The cortex was subdivided in 5 equal Bins -Bin1 corresponded to apical side and Bin5 to pial side of the cortex and GFP+ cells calculated in each Bin.",
    "ncbi_link": "GFP: 
Cstb: 25308"
  },
  {
    "caption": "K.Quantification of the total number of proliferating PH3+ cells/area(µm2)of ventricular structures transfected with GFP-empty vector control, GFP-Cstb or GFP-R68X mutant in (H).",
    "ncbi_link": "GFP: 
Cstb: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E16 mouse cerebral cortices electroporated at E14 with GFP-empty vector control, GFP-Cstb or GFP-R68X mutant, analyzed 2 dpe and immunostained with GFP and Tbr2. Ventricle (V) is indicated. The dashed lines represent the apical surface of the ventricles. Quantification of the total number of Tbr2+ cells/ cortical area (µm2) in (L). Data shown as Z-scores relative to the mean of GFP control vector.",
    "ncbi_link": "GFP: 
Cstb: 25308"
  },
  {
    "caption": "Micrograph of coronal sections of E17 mouse cerebral cortices electroporated at E14 co-electroporated with mCherry expressing vector and HA-Cstb or R68X, and analyzed 3 dpe. Immunostaining with RFP to identify electroporated cells and GFP to identify migrating interneurons in the GAD65-GFP transgenic mouse line. Ventricle (V) is indicated. The dashed lines represent the apical surface of the ventricles. Quantification of the total number of GAD65-GFP interneurons/ cortical area (µm2) in (N). Data shown as Z-scores relative to the mean of GFP control vector. Nuclei (blue) are stained with DAPI.",
    "ncbi_link": "GFP: 
HA: 
mCherry: 
Cstb: 25308
GAD65: 14417"
  },
  {
    "caption": "Results of the ELISAs used to determine IFN-β (A) secretion in PMA-differentiated THP-1 cells transfected with siCtrl, siRNF34-1, siRNF34-2 or siRNF34-3 oligos and infected with VSV for the indicated times. ELISA data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "Results of the ELISAs used to determine IL6 (B) secretion in PMA-differentiated THP-1 cells transfected with siCtrl, siRNF34-1, siRNF34-2 or siRNF34-3 oligos and infected with VSV for the indicated times. ELISA data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "Luciferase activity driven by the IFN-β (C) promoter in HEK293T cells transfected with Flag-RNF34 or its E3 ligase-dead mutant H342A followed by VSV infection for the indicated times. Luciferase assays were performed 24 hrs after transfection, and luciferase activity was reported as the fold induction. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "Flag: 
luciferase: 
IFN-β: 3456
RNF34: 80196"
  },
  {
    "caption": "Luciferase activity driven by the NF-κB (D) promoter in HEK293T cells transfected with Flag-RNF34 or its E3 ligase-dead mutant H342A followed by VSV infection for the indicated times. Luciferase assays were performed 24 hrs after transfection, and luciferase activity was reported as the fold induction. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "Flag: 
luciferase: 
NF-κB: 4791///4790
RNF34: 80196"
  },
  {
    "caption": "(E) Plaque assay of VSV loads in supernatants from cells transfected with shCtrl, shRNF34-1, shRNF34-2 or shRNF34-3 and subsequently infected with VSV. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(F) Microscopy images of shCtrl-, shRNF34-1-, shRNF34-2- or shRNF34-3 cells infected with NDV-GFP (MOI = 1.0) for the indicated times. Gray represents cells; green represents NDV. Scale bar, 300 μm.",
    "ncbi_link": "GFP: 
RNF34: 80196"
  },
  {
    "caption": "(G) Immunoblot showing the levels of the phosphorylated (p) and total IRF3, TBK1, and VSV-G proteins in PMA-differentiated THP-1 cells transfected with siCtrl or siRNF34-1 oligos and infected with VSV for the indicated times.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "RT-PCR analysis of the expression of the IFN-β (H) mRNAs in PBMCs transfected with siCtrl or siRNF34-1 oligos and infected with VSV for the indicated times. The results were normalized to the values obtained prior to VSV infection.",
    "ncbi_link": "IFN-β: 3456
RNF34: 80196"
  },
  {
    "caption": "(I) Results of the ELISA used to determine IFN-β secretion in PBMCs transfected with siCtrl or siRNF34-1 oligos and infected with VSV for the indicated times. ELISA data are presented as means ± SEM. Two-tailed Student's t-test was used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "RT-PCR analysis of the expression of the IL8, ISG54 and ISG56 (J) mRNAs in PBMCs transfected with siCtrl or siRNF34-1 oligos and infected with VSV for the indicated times. The results were normalized to the values obtained prior to VSV infection.",
    "ncbi_link": "IL8: 3576
ISG56: 3434
ISG54: 3433
RNF34: 80196"
  },
  {
    "caption": "(A) Luciferase activity driven by the ISRE promoter in HEK293T cells transfected with Myc-RNF34 and Flag-V, Flag-N-RIG-I, Flag-MAVS, Flag-STING or Flag-TBK1. Luciferase assays were performed 24 hrs after transfection. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-tests were used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "Flag: 
luciferase: 
Myc: 
STING: 
TBK1: 
N-RIG-I: 23586
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(B) Y2H analysis in the AH109 yeast strain co-transformed with the indicated plasmids. A positive RNF34-MAVS interaction resulted in colony formation on synthetic medium lacking tryptophan, leucine, adenine, and histidine containing X-gal. pGBKT7-TP53+pGADT7-T and pGBKT7-lam+pGADT7-T were used as positive and negative controls, respectively. AH109 co-transfected with pGBKT7-RNF34+pACT-2 was used to exclude the self-activation of RNF34.",
    "ncbi_link": "lam: 
T: 
RNF34: 80196
TP53: 24842"
  },
  {
    "caption": "(C) Immunoprecipitation analysis of HEK293T cells transfected with Myc-RNF34 and Flag-MAVS or Flag-V. Anti-Flag or IgG agarose immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(E) Anti-Flag or IgG immunoprecipitates prepared from cells transfected with Flag-MAVS or Flag-vector-expressing plasmids were subjected to SDS-PAGE and blotted onto a nitrocellulose membrane. The nitrocellulose membrane was incubated with soluble GST-RNF34 (upper panel) or GST (middle panel) for 2 hrs and then analyzed with anti-Flag antibody.",
    "ncbi_link": "Flag: 
MAVS: 57506"
  },
  {
    "caption": "(J) Immunoprecipitation analysis of HEK293T cells transfected with Myc-RNF34 and Flag-MAVS or Flag-mMAVS. Anti-Flag immunoprecipitates were analyzed using immunoblotting with anti-Myc or anti-Flag antibody.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
mMAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(A) Immunoprecipitation analysis in HEK293T cells expressing Flag-MAVS and Myc-Ub together with HA-RNF34 or HA-H342A. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody. The levels of the transfected proteins were analyzed using immunoblotting with an anti-HA, anti-Myc or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(B) Immunoprecipitation analysis of HEK293T cells expressing Flag-MAVS and HA-RNF34 together with Myc-Ub (K6, K11, K27, K29, K33, K48, or K63 only) as indicated. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody. Levels of the transfected proteins were analyzed using immunoblotting with an anti-HA, anti-Myc or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(C) Immunoprecipitation analysis of HEK293T cells expressing Flag-MAVS and HA-RNF34 together with Myc-Ub (wild-type, WT; Lys-to-Arg mutants of all Ub lysines, KO; K27/29R). Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody. Levels of the transfected proteins were analyzed using immunoblotting with an anti-HA, anti-Myc or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(E) Immunoprecipitation analysis of siCtrl- or siRNF34-1-transfected cells infected with VSV for the indicated times. Anti-MAVS immunoprecipitates were analyzed using immunoblotting with an anti-MAVS or anti-Ub-K27 antibody. The WCL was immunoblotted with an anti-MAVS or anti-Ub-K27 antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "Immunoprecipitation analysis of HEK293T cells expressing Flag-MAVS or Lys to Arg mutants together with Myc-Ub and HA-RNF34. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody. Levels of the transfected proteins were analyzed using immunoblotting with an anti-HA, anti-Myc or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "Immunoprecipitation analysis of HEK293T cells expressing Flag-MAVS or 4KR mutant together with Myc-Ub and HA-RNF34. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Ub-K27 antibody. Levels of the transfected proteins were analyzed by performing immunoblotting with an anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(C) Immunoprecipitation analysis of HEK293T cells expressing Flag-MAVS or K311R mutant together with HA-RNF34 and/or Myc-TRIM31 following a 3MA (0.2 mM) treatment. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Flag, anti-Ub-K63 or anti-Ub-K27 antibody. Levels of the transfected proteins were analyzed using immunoblotting with an anti-HA or anti-Flag antibody. ell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
MAVS: 57506
RNF34: 80196
TRIM31: 11074"
  },
  {
    "caption": "(D) Co-immunoprecipitation analysis of the ubiquitination of endogenous MAVS in THP-1 cells transfected with siCtrl, siRNF34, or siTRIM31 oligos and infected with VSV for the indicated times. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196
TRIM31: 11074"
  },
  {
    "caption": "(C) Immunoblot showing the levels of the MAVS protein in HEK293T cells expressing Flag-MAVS or Flag-mMAVS together with Myc-RNF34. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
mMAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(D) Immunoblot showing the levels of the MAVS protein in HEK293T cells expressing Flag-MAVS or its 4KR mutant together with increasing amounts of Myc-RNF34. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(E) Immunoblot showing the levels of the MAVS protein in HEK293T cells expressing Flag-MAVS with increasing amounts of HA-RNF34 or its H342A mutant. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(F) SDD-AGE analysis of MAVS aggregates in HEK293T cells expressing Flag-MAVS together with WT Myc-RNF34 or its ligase-dead mutant and cultured in the presence or absence of MG132 (10 μM), 3-MA (1 mM) or NH4Cl (3 mM). SDS-PAGE immunoblotting was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
RNF34: 80196"
  },
  {
    "caption": "(G) SDD-AGE analysis of MAVS aggregates in siCtrl- or siRNF34-1-transfected cells using an anti-MAVS antibody. SDS-PAGE immunoblotting was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(H) Immunoblot showing the levels of the MAVS protein in siCtrl- or siRNF34-1-transfected PBMCs. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(I) SDD-AGE analysis of MAVS aggregates in THP-1 cells expressing Flag-MAVS or the K311R mutant together with Myc-RNF34 or Myc-TRIM31. SDS-PAGE immunoblotting was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
Myc: 
MAVS: 57506
RNF34: 80196
TRIM31: 11074"
  },
  {
    "caption": "(A) Immunoprecipitation analysis of HEK293T cells transfected with Flag-SQSTM1 or its I431A mutant together with HA-MAVS. Anti-Flag or IgG agarose immunoprecipitates were analyzed using immunoblotting with an anti-HA or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
MAVS: 57506
SQSTM1: 8878"
  },
  {
    "caption": "(B) Luciferase activity driven by the IFN-β promoter in HEK293T cells transfected with HA-MAVS or its 4KR mutant together with Flag-SQSTM1 or its I431A mutant. Luciferase assays were performed 24 hrs after transfection. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-tests were used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "Flag: 
HA: 
luciferase: 
IFN-β: 3456
MAVS: 57506
SQSTM1: 8878"
  },
  {
    "caption": "(C) Immunoblot showing the levels of the MAVS protein in HEK293T cells expressing HA-MAVS or its 4KR mutant together with Flag-SQSTM1. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
MAVS: 57506
SQSTM1: 8878"
  },
  {
    "caption": "(D) Luciferase activity driven by the IFN-β promoter in HEK293T cells transfected with HA-MAVS or its 4KR mutant together with Flag-NDP52 or its D439R/C443K mutant. Luciferase assays were performed 24 hrs after transfection. The luciferase reporter data are presented as means ± SEM. Two-tailed Student's t-tests were used for statistical analyses: *, P < 0.05; **, P < 0.01; and ***, P < 0.001.",
    "ncbi_link": "Flag: 
HA: 
luciferase: 
NDP52: 10241
IFN-β: 3456
MAVS: 57506"
  },
  {
    "caption": "(E) Immunoprecipitation analysis of HEK293T cells transfected with Flag-MAVS or its 4KR mutant together with Myc-NDP52. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-Myc or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
Myc: 
NDP52: 10241
MAVS: 57506"
  },
  {
    "caption": "(G) Immunoprecipitation analysis of the interaction between Flag-NDP52 and HA-RNF34 in WT or MAVS-/- cells. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-HA antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "MAVS: 57506"
  },
  {
    "caption": "(H) Immunoprecipitation analysis of HEK293T cells transfected with Flag-NDP52 or its D439R/C443K mutant together with HA-MAVS followed by VSV infection. Anti-Flag immunoprecipitates were analyzed using immunoblotting with an anti-HA or anti-Flag antibody. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
HA: 
NDP52: 10241
MAVS: 57506"
  },
  {
    "caption": "(I) Immunoblot showing the levels of the MAVS protein in siCtrl- or siNDP52-transfected cells expressing Flag-RNF34 or Flag-V. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
NDP52: 10241
RNF34: 80196"
  },
  {
    "caption": "(J) Immunoblot showing the levels of the MAVS protein in siCtrl- or siNDP52-transfected cells infected with VSV (MOI = 1, 12 hrs). α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(K) Immunoprecipitation analysis of the MAVS-LC3 interaction in siCtrl- or siNDP52-transfected cells infected with VSV. Anti-MAVS immunoprecipitates were analyzed using immunoblotting with an anti-MAVS or anti-LC3 antibody. NDP52 levels were analyzed by performing immunoblotting with an anti-NDP52 antibody. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(A) Immunoblot showing MAVS, IRF3-p, LC3, TOM20 and HSP60 levels in siCtrl- or siRNF34-1 cells infected with VSV and cultured in the presence of Z-VAD (50 μM) for the indicated times. α-Tubulin was used as a loading control. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(B) Immunoblot showing MAVS, LC3, TOM20 and HSP60 levels in cells transfected with Flag-RNF34 or its H342A mutant and subsequently infected with VSV for the indicated times. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "Flag: 
RNF34: 80196"
  },
  {
    "caption": "Representative confocal images (C) of immunofluorescence staining for NDP52 colocalization with MAVS in shCtrl- or shRNF34-1 cells infected with VSV for the indicated times. Red represents MAVS and green represents NDP52. Scale bar, 10 μm. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "quantification (D) of immunofluorescence staining for NDP52 colocalization with MAVS in shCtrl- or shRNF34-1 cells infected with VSV for the indicated times. Scale bar, 10 μm. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(E) Transmission electron microscopy images of shCtrl- and shRNF34-1 HEK293T cells cultured in the presence or absence of VSV. Arrows indicate mitochondria engulfed in autophagosomes. Double arrows indicate swollen mitochondria with disrupted cristae. M, mitochondria and N, nucleus. 40000× magnification. Cell-based studies were performed independently at least three times with comparable results.",
    "ncbi_link": "RNF34: 80196"
  },
  {
    "caption": "(G) (left) Western blot of pERK in TNERT, TNERTFgfr1-/-, TNERTFgfr2-/-, TNERTFgf4-/-, and TNERTFgfbp1-/- with or no OHT. (Right) relative pERK levels estimated by densitometry  (n=4). Data information: n ≥ 3 biological replicates (each dot represents a biological replicate). Data are presented as mean ± SEM in G, *P < 0.05, **P < 0.01, ***P < 0.001, and ns = not significant (paired two-tailed student's t-test).",
    "ncbi_link": "Fgf4: 14175
Fgfbp1: 14181
Fgfr1: 14182
Fgfr2: 14183"
  },
  {
    "caption": "(C) Western blot of pERK and ERK in TNERT  and  TNERTNono-/- cells treated with or no OHT  (n=3).",
    "ncbi_link": "Nono: 53610"
  },
  {
    "caption": "(D) Immunoprecipitation  analysis showing interactions between ERK and NONO  in the presence or absence of Nanog  induction by Doxycycline  in TDiN  cells.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "(E) 293T cells were infected with ULK1 shRNA or control shRNA lentiviruses and subjected to immunoprecipitation with control rabbit IgG or anti-AMPKα antibody followed by immunoblotting with anti-ULK1 and anti-AMPKα antibodies.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(B) U-2OS cells stably expressing GFP-LC3 were infected with lentivirus expressing human Ulk1 shRNA (shhUlk1) or scrambled shRNA (shScr) and subjected to selection with 1 µg/ml puromycin for 5 days. The cells were then transfected with wild type mouse Ulk1 (mUlk1), mUlk1 Δ654-828 or control empty vector for 24 h, incubated in serum-free DMEM overnight, and cultured in complete medium with or without 10 mM metformin for 20 h. The images were obtained using a fluorescence microscope. The scale bars represent 10 µm.",
    "ncbi_link": "Ulk1: 8408
Ulk1: 22241"
  },
  {
    "caption": "(A) TSC2−/−, p53−/− MEFs stably reconstituted with wild-type raptor or S722A/S792A mutant raptor were transfected with GFP-LC3, treated with 2 mM AICAR or control vehicle for 4 h, and then analyzed by fluorescent microscopy. The number of GFP-LC3 dots per GFP-positive cell was counted (mean ± s.d.; n = 60). The scale bars represent 10 µm.",
    "ncbi_link": "p53: 22059
TSC2: 22084"
  },
  {
    "caption": "(B) TSC2−/−, p53−/− MEFs stably reconstituted with wild-type raptor or S722A/S792A mutant raptor were treated with 2 mM AICAR for the indicated times. Cell lysates were prepared in RIPA buffer and analyzed by immunoblotting with the indicated antibodies. The levels of p62 are listed relative to those of untreated WT raptor cells, which were set as 1.",
    "ncbi_link": "p53: 22059
TSC2: 22084"
  },
  {
    "caption": "E. Quantification of the nociceptive responses within 5 min after intraplantar injection of control saline in WT mice or 500 ppm iodine in WT and TRPA1-/-mice.",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "F. Quantification of the nociceptive responses in TRPA1-/- mice within 5 min after intraplantar injection of control saline or 1,000 ppm iodine, following intraperitoneal injection of saline or vehicle.",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "A. Left, time course of ear swelling elicited by topical application of 5% PVP-I solution in 0.15% Oxa-challenged WT and TRPA1-/-mice, or 5% povidone solution in Oxa-challenged WT mice. In this and subsequent similar figures, the number of mice is indicated. Right, bar graph highlighting the response at 24 h shown at left.",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "C. Time course of ear swelling elicited by topical application of 3% iodine in 0.15% Oxa-challenged WT and TRPA1-/-mice, and bar graph highlighting the response at 24 h.",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "D. Hematoxylin and eosin stained tissue sections of iodine treated ear in 0.15% Oxa-challenged WT and TRPA1-/-mice (n ≥ 3).",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "E. Time course of ear swelling elicited by topical application of 3% iodine in 0.15% Oxa-challenged TRPA1-/-mice, following intraperitoneal injection of AMG517 or vehicle, and bar graph highlighting the response at 24 h.",
    "ncbi_link": "TRPA1: 277328"
  },
  {
    "caption": "A. Representative intracellular Ca2+ signals in hTRPA1-expressing HEK293 cells in response to different concentrations of iodine. 2-APB, a TRPA1 agonist, was subsequently applied to fully activate TRPA1. RFU: relative fluorescence unit.",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "B. Concentration-response relationships of iodine-induced intracellular Ca2+ increase in HEK293 cells expressing WT or mutant TRPA1 channels. Data are presented as mean ± s.e.m. n ≥ 8 for each construct at each concentration. The smooth curves are fits to the Hill equation.",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "C. Time course of iodine-induced currents in hTRPA1-expressing Xenopus oocytes. HC: HC030031",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "D. Concentration-response relationship of iodine-induced currents in hTRPA1-expressing Xenopus oocytes. Data are presented as mean ± s.e.m. n ≥ 8 for each concentration. The smooth curve is a fit to the Hill equation.",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "E. Time course of intracellular iodine-induced macroscopic currents in an inside-out patch from hTRPA1-expressing HEK293 cell (n = 3).",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "F. Time course of iodine-induced currents in a hTRPA1-expressing Xenopus oocyte, which presents the current reduction upon DTT treatment (n = 3).",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "G, H. Comparisons of the iodine-induced whole-cell current in HEK293 cells expressing WT hTRPA1 (G) or the triple mutant channel (C421S/K710R/C856S) (H) (n ≥ 4).",
    "ncbi_link": "TRPA1: 8989"
  },
  {
    "caption": "I. Representative whole-cell currents in HEK293 cells expressing human TRPV1 in response to iodine and subsequently applied capsaicin (n = 3).",
    "ncbi_link": "TRPV1: 7442"
  },
  {
    "caption": "HO-1 expression on mRNA level quantified by qPCR qPCR analysis based on two independent experiments n = 10-11/group",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "HO-1 expression on mRNA level quantified by RNA-seq. RNAseq analysis has n = 3-4/group, two-tailed t-test for two groups comparison, and one way ANOVA with Bonferroni post-test for multiple group comparison. *p< 0.05, ****p< 0.0001. Data are shown as mean ± SEM.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Middle-aged animals have lower frequency of ECs. Two independent experiments, n = 10-11/group. Data are shown as mean ± SEM. **p<0.01, two-tailed unpaired t-test. The control staining of HO-1 on HO-1-/- bone marrow section is provided in Appendix Fig S1.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "RNA-seq revealed 111 DEGs in HO-1-/- ECs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "The identified DEGs separated HO-1-/- and HO-1+/+ ECs by (B) hierarchical clustering and (C) PCA.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Heatmap of selected (E) hematopoietic factors and (F) adhesion molecules expression in HO-1-/- and HO-1+/+ ECs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "RNA-seq revealed 100 DEGs in HO-1-/- CARs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "The identified DEGs separated HO-1-/- and HO-1+/+ CARs by (H) hierarchical clustering and (I) PCA.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Heatmap of selected (K) skeletal biology and (L) hematopoietic factors expression in HO-1-/- and HO-1+/+ CARs. Correlation similarity metric and average linkage clustering were used in the presented heatmaps.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "HO-1-/- mice have more ECs and less CARs (p = 0.053) in BM, while frequency of PaS does not differ.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Young HO-1-/- mice have lower frequency of Sca-1high fraction among BM ECs, what resembles phenotype of BM ECs in old mice.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Intracellular flow cytometry reveals (C) lower levels of SDF-1α in HO-1-/- CARs and (D) lower levels of LAP protein in HO-1-/- ECs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Analysis of cell surface SCF revealed lower frequency of SCF+ ECs in HO-1-/- while no differences among CARs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "The frequency of (F) CD163+ MQs and (G) CD163- MQs in BM of HO-1-/- mice is altered.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Young HO-1-/- mice possess higher number of (B) LT-HSCs, (C) ST-HSCs and (D) MPPs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "More young HO-1-/- LT-HSCs are in G1 and S/G2/M cell cycle phases. The presented cell cycle analysis is from two independent experiments. Young HO-1-/- MPPs do not differ in cell cycling from young HO-1+/+ MPPs. The presented cell cycle analysis is from two independent experiments. More old HO-1-/- LT-HSCs are in G1 phase in comparison to old HO-1+/+ LT-HSCs, but not in S/G2/M phase. The presented cell cycle analysis is from two independent experiments. Old MPPs do not differ in cell cycling between genotypes. The presented cell cycle analysis is from two independent experiments.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Young HO-1-/- LT-HSCs contain more γH2aXhigh cells than young HO-1+/+, 378-991 cells analyzed from 7 mice/group. Young HO-1-/- MPPs contain more γH2aXhigh cells than young HO-1+/+, 1693-2790 cells analyzed from 7 mice/group.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Alkaline comet assay revealed that HO-1-/- LT-HSCs possess (L) higher oil tail moment and (M) more DNA in the comet tail. 1068-1189 cells analyzed from 6 mice/group.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "HSCs from young HO-1-/- mice provide worse hematopoietic reconstitution after transplantation than HO-1+/+ HSCs. Data are shown as mean ± SEM, n = 8-9 mice/group.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "RNA-seq revealed 1067 DEGs between young HO-1-/- and HO-1+/+ LT-HSCs. RNA-seq revealed 595 DEGs between old HO-1-/- and HO-1+/+ LT-HSCs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "PC1 in PCA analysis on selected 1148 genes separated young HO-1+/+ LT-HSCs from other groups, clustering the young HO-1-/- LT-HSCs together with old LT-HSCs.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Hierarchical clustering on the 20% of most correlated 297 genes with PC1 showed 2 major clusters that includes young HO-1+/+ LT-HSCs in one and old LT-HSCs with young HO-1-/- LT-HSCs in second.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Deletion of HO-1 in myeloid lineage did not cause expansion of LT-HSCs and did not alter their cell cycle status.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Long-term PB chimerism derived from HSCs transplanted to HO-1-/- recipients is lower than from HSCs transplanted to HO-1+/+ recipients.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Chimerism among BM HSPCs fractions transplanted to HO-1-/- recipients are lower than from HSCs transplanted to HO-1+/+ recipients. Data are shown as mean ± SEM, n = 5-12/group",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "total number of cells derived from HSCs transplanted to HO-1-/- recipients are lower than from HSCs transplanted to HO-1+/+ recipients. Data are shown as mean ± SEM, n = 5-12/group",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Short term homing of HSPC to HO-1+/+ or HO-1-/- BM did not differ. Data are shown as mean ± SEM, n = 5/group, unpaired t-test.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Transplantation of HO-1-/- HSCs provides lower chimerism among HSPC fractions in primary recipients. Data are shown as mean ± SEM, n = 7-8 mice/group.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Comparison of gene log fold changes in non-transplanted HO-1-/- LT-HSCs and HO-1-/- LT-HSCs transplanted twice to the wild-type HO-1+/+ showed that transplantation of HO-1-/- LT-HSCs twice to the wild type niche reverses their transcriptional alterations.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Frequency of colonies appearing at day 8 and day 12 from HSCs co-cultured with HO-1+/+ or HO-1-/- MSCs. *p< 0.05, ***p<0.001, Fisher exact test.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Analysis of frequency of colonies derived from HO-1+/+ or from HO-1-/- MSC co-cultures among identified clusters. Enrichment in cluster analyzed by Fisher exact test, **p<0.01, two-tailed unpaired t-test.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Sdf1α mRNA levels in BM of HO-1+/+ or HO-1-/- mice after administration of Noggin. Data are shown as mean ± SEM. *p< 0.05, two-tailed unpaired t-test, n = 10/group",
    "ncbi_link": "Sdf1α: 20315
HO-1: 15368"
  },
  {
    "caption": "LT-HSC frequency of LT-HSCs after administration of Noggin to HO-1+/+ or HO-1-/- mice. Data are shown as mean ± SEM. *p< 0.05, **p<0.01, two-tailed unpaired t-test, n = 8-10/group",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "cell cycling status of LT-HSCs after administration of Noggin to HO-1+/+ or HO-1-/- mice.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "A: Brightfield images of a NTH-KO and NTH/GFP ookinete, showing normal ookinete morphology, but lack of pigment clusters associated with crystalloids (arrows) in the NTH null mutant. Scale bar = 5μm.",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "B: Aligned dot plot of oocyst numbers in Anopheles stephensi infected with parasite lines NTH/GFP, NTH-KO and NTH∆PP. Horizontal lines mark mean values (n=20); ns, not significantly different (Mann-Whitney).",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "C: Brightfield and fluorescence images of oocysts of parasite lines NTH/GFP and NTH-KO at 15 days post-infection, showing lack of sporulation in the NTH null mutant. Hoechst DNA staining (artificially depicted red) labels parasite nuclei. The large nuclei of the epithelial midgut cells also show. Scale bar = 20μm.",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "D: Aligned dot plot of oocyst diameters in Anopheles stephensi at 15 days post-infection with parasite lines NTH/GFP, NTH-KO and NTH∆PP. Horizontal lines mark mean values (n=20). ** mark statistically significant differences (P<0.0001, Mann-Whitney); ns, not significant.",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "E: Images of ookinetes of parasite lines NTH∆PP showing dispersed NTH∆PP::GFP fluorescence; LAP3/mCherry showing focal LAP3::mCherry fluorescence in crystalloids; Cross (carrying modified alleles encoding NTH∆PP::GFP and LAP3::mCherry), showing dispersed LAP3::mCherry fluorescence. Arrow marks pigment cluster associated with crystalloids. Scale bar = 5μm.",
    "ncbi_link": "LAP3: 
mCherry: 
NTH: 3424314"
  },
  {
    "caption": "G: PCR diagnostic for the presence of modified nth alleles in blood stage infections obtained after sporozoite transmission of a NTH∆PP x LAP3/mCherry genetic cross (lane NTH∆PP), amplifying an approximately 4.4kb fragment. NTH/GFP parasites are used as a PCR control, amplifying approximately 4.6kb. Parental parasites provide a negative control.",
    "ncbi_link": "GFP: 
LAP3: 
mCherry: 
nth: 3424314
NTH: 3424314"
  },
  {
    "caption": "A: Brightfield and fluorescence image of an unsporulated NTH/GFP oocyst at 15 days post-infection. Scale bar = 20μm. B: Image of a sporulated NTH/GFP oocyst at 15 days post-infection. Scale bar = 20μm. ",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "C: Image of a NTH/GFP sporozoite, showing NTH::GFP localisation in a tubular structure. Scale bar = 10μm.",
    "ncbi_link": "GFP: 
NTH: 3424314"
  },
  {
    "caption": "E: Image of sporozoites expressing NTH::GFP (green) and ACP::mCherry (red), showing co-localization in the apicoplast (arrows). Sporozoites expressing only ACP::mCherry or NTH::GFP are also present. Scale bar = 10μm.",
    "ncbi_link": "GFP: 
mCherry: 
ACP: 3424006
NTH: 3424314"
  },
  {
    "caption": "Purified CUL3WT and CUL3Δ403-459 analysed by SDS-PAGE and Coomassie blue staining, following expression in SF21 cells, and DAC-tag-affinity purification and tag cleavage (see Materials and Methods). Bands migrating between 62- and 98-kDa protein markers are CUL3WT and CUL3Δ403-459, respectively, while the band below 17 kDa is Rbx1. The immunoblot for RBX1 is shown on the right. The band in CUL3WT denoted with * is co-purified insect cell CAND1, which was later removed by SEC. All protein identities were confirmed by mass spectrometry.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "KLHL3 binding to CUL3WT and CUL3Δ403-459 is comparable as shown by pull-down assays with a KLHL3 resin generated from cross-linking anti-KLHL3 antibody to Protein G sepharose, and then binding saturating amounts of KLHL3 to the anti-KLHL3 resin (denoted KLHL3R), the control resin (ControlR) is Protein G sepharose (see Materials and Methods for further detail). CUL3WT or CUL3Δ403-459 was incubated with either KLHL3R or ControlR at 4°C for 1 h and then washed thrice with 1× PBS, resin volumes were minimised, and SDS-Laemmli buffer was used to elute protein from resin prior to analysis by SDS-PAGE and staining with colloidal blue.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "UBE2D3˜ubiquitin-release assays analysed by non-reducing SDS-PAGE and immunodetection. His-tagged UBE2D3 was charged with ubiquitin by incubation with ATP and UAE, and charging was stopped by ATP depletion with apyrase. No CUL3 (negative control, lane 1), CUL3WT or CUL3Δ403-459 was then added to the charged E2 and the activity of the RING domain, RBX1, monitored by the hydrolysis of ubiquitin from UBE2D3, visualised by immunodetection with anti-His antibody (upper panel, \"˜\" denotes thioester bond). The lower panel is an immunoblot for CUL3, showing equivalent amount of both CUL3WT and CUL3Δ403-459 was added to the reaction mix; over time, the appearance of higher molecular weight bands represents the modification of CUL3 by covalent attachment of ubiquitin. The right two lanes are control lanes incubated for 10 min with E2˜Ubi but then treated with reducing agent prior to SDS-PAGE.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "Time course of in vitro neddylation reactions. Purified NAE, UBE2M and Nedd8 were mixed with either CUL3WT or CUL3Δ403-459 and incubated at 30°C for the time indicated. Due to the covalent attachment of Nedd8 (8.6 kDa), modified proteins have decreased mobility. The band shift observed for CUL3WT (lane 1 versus lane 2) is representative of a single Nedd8 modification, while the multiple bands in the CUL3Δ403-459 reaction reflect the attachment of up to three Nedd8 molecules (lane 5 versus lane 8).",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "HEK-293 cells over-expressing either FLAG-CUL3WT or FLAG-CUL3Δ403-459 were immunoprecipitated with M2 Flag-binding sepharose, in the presence of a deneddylase inhibitor (OPT). Extract, cells were lysed in the presence of OPT and clarified by centrifugation. IP:M2, clarified supernatant samples were incubated for 1 h at 4°C with M2 (anti-Flag) sepharose, then washed with PBS and eluted with SDS-Laemmli buffer, prior to SDS-PAGE and immunodetection with anti-FLAG antibody. Bands are labelled as follows: 1. CUL3WT, 2. CUL3WT-N8, 3. CUL3Δ403-459, 4. CUL3Δ403-459-N8, 5. CUL3Δ403-459-2(N8).",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "Neddylation in HEK-293 cells over-expressing FLAG-CUL3WT or FLAG-CUL3Δ403-459 was blocked by treatment with a Nedd8-E1-enzyme inhibitor, 3 μM MLN4924 (Millennium Pharmaceuticals), in cells over-expressing FLAG-CUL3WT and FLAG-CUL3Δ403-459 respectively. Cell extracts were sampled over time in the presence of OPT to prevent de-neddylation and subjected to SDS-PAGE and immunodetection of the FLAG tag.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "FLAG-CUL3WT or FLAG-CUL3Δ403-459 was immunoprecipitated with M2-sepharose as described in (F). +MLN4924 indicates cell culture media supplementation with 3 μM MLN4924 for 5 h prior to cell lysis to achieve complete deneddylation of CUL3. Following SDS-PAGE, immunoblotting with COP9 Signalosome (CSN) or CAND1 antibodies determined the interaction between these Cullin regulators and FLAG-CUL3WT and FLAG-CUL3Δ403-459, respectively.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "GST-CAND1 pull-down assays with CUL3 proteins. Purified GST or GST-CAND1 immobilised on glutathione-sepharose was mixed with either purified CUL3WT or CUL3Δ403-459 and incubated at 4°C for 1 h. The sepharose was then washed thrice and eluted from the resin by incubation with SDS-Laemmli buffer prior to SDS-PAGE and Coomassie staining. CUL3WT but not CUL3Δ403-459 interacts with CAND1.",
    "ncbi_link": "CAND1: 55832
CUL3: 8452"
  },
  {
    "caption": "A-D In vitro ubiquitylation assays with purified proteins. As ubiquitin is covalently attached to the substrate lysine residue, the appearance of higher molecular weight protein bands reflects the modification of the protein with ubiquitin. All assays contain purified UBE1, UBE2D3, ubiquitin, 0.1 mM ATP, 1 mM MgCl2 and were buffered in 50 mM HEPES, 150 mM NaCl and incubated at 30°C for the time indicated. Reactions were stopped by the addition of SDS-Laemmli buffer to a concentration of 1×. SDS-PAGE, staining with Coomassie blue, or detection with the indicated antibody following immunoblotting enabled the visualisation of ubiquitylation. (A) to determine the relative modification of KLHL3 by CUL3WT and CUL3Δ403-459, KLHL3 was included into the reaction at 2× molar concentration over CUL3WT and CUL3Δ403-459. (B, C) Reactions serve to determine basal auto-ubiquitylation of CUL3WT or CUL3Δ403-459 and do not contain KLHL3 or other potential substrate proteins. Lysine residues on CUL3WT or CUL3Δ403-459 act as the substrate. (B) High molecular weight bands reflect ubiquitin chain linkages on CUL3 or the multiple mono-ubiquitylation of a number of CUL3 lysine residues. (C) Activity assays contain methylated ubiquitin, a form of ubiquitin incapable of forming ubiquitin chains; as such, higher band shifts reflect the attachment of mono-ubiquitin to one more lysine residue on CUL3WT or CUL3Δ403-459, respectively. (D) Activity assay performed as in (C) with methyl-ubiquitin, the boxes shown on the gel are indicative of the gel pieces excised for mass spectrometry analysis in (F).",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "A-C In vitro ubiquitylation assays were performed as described in Figure 2, but with the addition of immunoprecipitated over-expressed FLAG-WNK4 in (B, C) (see Materials and Methods). The WNK kinases are modified by CUL3WT-KLHL3, with the higher molecular weight smear observed in anti-WNK1 and anti-FLAG panels representative of multiple ubiquitin molecules being covalently attached to the WNK protein. CUL3Δ403-459 is unable to modify WNKs. Samples from the same assay reactions were divided to allow immunodetection of the different protein components modified within the same assay reaction. (C) CUL3WT, CUL3Δ403-459 and an equimolar solution CUL3WT:CUL3Δ403-459 (1:1 Mix) were incubated with KLHL3 and immunoprecipitatedFLAG-WNK4 in ubiquitylation reactions to determine the influence of CUL3Δ403-459 on the ubiquitylation activity of CUL3WT. Notably, the presence of CUL3Δ403-459 does not inhibit WNK ubiquitylation by CUL3WT.In vitro ubiquitylation assays with purified proteins. As ubiquitin is covalently attached to the substrate lysine residue, the appearance of higher molecular weight protein bands reflects the modification of the protein with ubiquitin. All assays contain purified UBE1, UBE2D3, ubiquitin, 0.1 mM ATP, 1 mM MgCl2 and were buffered in 50 mM HEPES, 150 mM NaCl and incubated at 30°C for the time indicated. Reactions were stopped by the addition of SDS-Laemmli buffer to a concentration of 1×. SDS-PAGE, staining with Coomassie blue, or detection with the indicated antibody following immunoblotting enabled the visualisation of ubiquitylation.",
    "ncbi_link": "CUL3: 8452"
  },
  {
    "caption": "Western blot of whole kidney lysates from mice culled after a minimum 4-h fast. Following exsanguination after surgery, mouse tissues were rapidly harvested and stored, samples were then homogenised, clarified and quantified prior to SDS-PAGE. Immunodetection with the antibodies shown highlights elevated signalling through the WNK kinase pathway in CUL3WT/Δ403-459 versus CUL3WT mice. The lowest panel is an anti-CUL3 immunoprecipitation of the kidney lysate samples, whereby the CUL3 antibody was cross-linked to Protein G sepharose and used to affinity purify CUL3WT and CUL3Δ403-459 from kidney lysates. The samples were incubated together overnight to allow deneddylation of CUL3 proteins to occur and maximise CUL3 binding to the anti-CUL3 resin. Samples were thoroughly washed and eluted from the resin prior to SDS-PAGE and immunodetection for CUL3. The IP highlights that CUL3Δ403-459 is indeed present within the kidney lysate.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Plasma aldosterone after a minimum 4-h fast was calculated by HTRF (homogeneous time-resolved fluorescence) aldosterone assay. The average aldosterone level per mouse was calculated from duplicate samples run in parallel on the assay. Blood was rapidly harvested in heparin-coated plasma extraction tubes following exsanguination after surgery, and samples were snap-frozen for storage. A 58% increase in aldosterone was detected in CUL3WT/Δ403-459 versus CUL3WT mice (*P = 0.0245). Two-tailed unpaired Student's t-test; data are mean ± SEM.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Arterial blood biochemistries after a minimum 4-h fast. Under anaesthesia, the right carotid artery was cannulated to minimise atmospheric exposure of samples collected for iSTATbloodgas and electrolyte measurements. CUL3WT/Δ403-459mice present with abnormal electrolyte homoeostasis compared to CUL3WTmice, exhibiting hyperkalaemia (***P = 0.0004) and hyperchloraemia (***P = 9.5 × 10−5) with a compensated metabolic acidosis (P = 0.7766), marked by a decrease in bicarbonate () (***P = 3.4 × 10−5), base excess (BE) (***P = 9.1 × 10−5) and partial pressure of carbon dioxide (pCO2) (***P = 0.0038). Two-tailed unpaired Student's t-test; data are mean ± SEM.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Representative pseudocoloured maximum-intensity z projections of immunofluorescence stained kidney sections showing the distribution of the WNK/SPAK pathway components between CUL3WT/Δ403-459 and CUL3WTmice at a minimum 4-h fasting baseline (n = 4 per genotype). CUL3 and KLHL3 are comparable between genotypes, with significantly higher levels of CUL3 in the proximal convoluted tubule (PCT) compared to the weak staining in distal convoluted tubule (DCT) and thick ascending limb of the loop of Henle (TAL), while KLHL3 shows higher expression in the DCT/TAL cytosol with staining of the PCT confined to the apical membrane. Total (t) and phospho (p) NCC Thr44 and SPAK Thr243 show increased apical membrane expression in the parvalbumin (PVALB)-positive early and late (PVALB-negative) DCT of CUL3WT/Δ403-459mice. Unexpectedly, the increased levels of WNK4 and SPAK resulted in the formation of discrete puncta specifically in the DCT of CUL3WT/Δ403-459mice. It is possible that the autophagy-lysosomal system may attempt to compensate and degrade these excess proteins although the WNK4 puncta do not colocalise with the lysosomal marker LAMP1. Scale bar, 20 μm.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Continuous blood pressure measurements were taken in mice under general anaesthesia with thermostatically controlled body temperature, right carotid artery pressure transducer catheterisation and ECG Lead II heart rate monitoring. CUL3WT/Δ403-459 mice have elevated systolic (SBP) (***P = 1 × 10−12) and diastolic (DBP) blood pressure (***P = 8.5 × 10−8), although they also present with 7% lower heart rates (*P = 0.0485) when compared to CUL3WT mice. Two-tailed unpaired Student's t-test; data are mean ± SEM.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Pulse waveform analysis of blood pressure traces obtained in (A) reveals that CUL3WT/Δ403-459 mice have an increased pulse pressure (PP) [SBP - DBP] (***P = 2.1 × 10−10), augmentation pressure (AP) [SBP - anacrotic notch (AN) pressure] (***P = 3.5 × 10−6), dicrotic notch (DN) pressure (***P = 4.7 × 10−13) and mean arterial pressure (MAP) [1/3 × SBP + 2/3 × DBP] (***P = 1.3 × 10−9). This hypertensive phenotype is in part due to changes in vascular contractility in CUL3WT/Δ403-459 mice as evidenced by their higher augmentation index (AIx) [AP/PP] (**P = 0.0096), a marker of arterial stiffness, and is further supported by an increase in their diastolic pressure decay time constant (τbourgeois) [1/slope of diastolic pressure decay; measured 30 ms after DN and 20 ms before end DBP] (**P = 0.0083), a surrogate marker of increased vascular resistance. Two-tailed unpaired Student's t-test; data are mean ± SEM",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "In vivo dose-responses to phenylephrine and angiotensin II. After baseline measurements were obtained from mice in (A), the right external jugular vein was cannulated for administration of bolus doses of vasopressors in increasing half-log steps. Dose-response curves were generated and data analysed using a logistical function to determine the estimated dose producing half-maximal response (ED50) and maximum response (Emax). The fitted Emax for phenylephrine was increased in CUL3WT/Δ403-459 versus CUL3WT (183.9 ± 2.5 versus 164.9 ± 1.4 mmHg) (***P = 1 × 10−6) indicating an increased vasoconstrictor response to adrenergic stimulation elevating systolic blood pressure substantially above the CUL3WT maximum. Similarly, the fitted Emax for angiotensin II stimulation was higher in CUL3WT/Δ403-459 versus CUL3WT (155.5 ± 1.8 versus 138.3 ± 2.2 mmHg) (***P = 1.7 × 10−6). However, there was no change between CUL3WT/Δ403-459 versus CUL3WT sensitivity (as measured by ED50) to phenylephrine (36.6 ± 5.1 versus 31.4 ± 2.8 μg/kg bw) (P = 0.3778) or angiotensin II (0.77 ± 0.16 versus 0.93 ± 0.13 μg/kg bw) (P = 0.4401). Two-tailed unpaired Student's t-test; data are mean ± SEM.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Western blot of tunica media-intimathoracic aorta lysates from mice culled after a minimum 4-h fast. Following exsanguination after surgery, mouse tissues were rapidly harvested and the tunica adventitia removed before storage, and later, the samples were homogenised, clarified and quantified prior to SDS-PAGE. Western blot analysis confirmed the expression of KLHL3 and CUL3. Similar to the kidney, the aorta of CUL3WT/Δ403-459 showed slightly lower levels of CUL3 compared to CUL3WT without any change in KLHL3 levels.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Representative maximum-intensity z projections of immunofluorescence stained thoracic aorta sections showing the distribution of CUL3 and KLHL3 between CUL3WT/Δ403-459 and CUL3WT mice at a minimum 4-h fasting baseline (n = 4 per genotype). CUL3 and KLHL3 localisation is comparable between genotypes. The highest levels were detected in the vascular smooth muscle cells and endothelium, with a minimal expression in the perivascular adipose tissue of the adventitia. Scale bar, 50 μm.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "Morphometric analysis of thoracic aortae reveals vascular remodelling in CUL3WT/Δ403-459 mice. There is an increase of ˜21% in the vessel wall intima-media thickness (demarcated by arrows) of CUL3WT/Δ403-459 compared to CUL3WT mice (***P = 0.0003). However, there is no change in the number of elastin laminae (P = 0.1458) and therefore no increase in the number of medial muscle layers between genotypes. Two-tailed unpaired Student's t-test; data are mean ± SEM.",
    "ncbi_link": "CUL3: 26554"
  },
  {
    "caption": "A qPCR  analysis of relative SCTR  levels in different tissues [heart  (He), intestine  (Int),  inguinal WAT (Ing), epididymal WAT (Ep), brown fat adipose  (BAT), liver  (Liv), hypothalamus  (Hypo), placenta  (Pla), skeletal muscle (Mus), kidney  (Kid)] from C57BL/6J mice  as indicated (n = 5 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. **p < 0.01; ***p < 0.001.",
    "ncbi_link": "SCTR: 319229"
  },
  {
    "caption": "B Change of  body weight  of M-SCT  floxed and M-SCT  KO mice  upon HFD  feeding (n = 8 per group). Right part shows representative photograph of M-SCT  floxed and M-SCT  KO mice  with HFD. Data information: Statistical significance was determined using Two-tailed Student's t test.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "C The weight  of different tissues from M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "D Random blood glucose  levels in M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 8 per group). E Insulin  levels in M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "F Intraperitoneal glucose tolerance test  (GTT) (1.0 g glucose/ kg body weight) in M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 5 per group) and AUCs were calculated. Mice  were fasted for 18h before assay. G Intraperitoneal insulin tolerance test (ITT) (0.75 U insulin/kg body weight) in M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 5 per group) and AUCs were calculated. mice  were fasted for 6h before assays. Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "H Serum TG, TC  and NEFA  levels in M-SCT  floxed and M-SCT  KO mice  with HFD  (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "A, B Time-resolved oxygen  consumption (A) and heat production  (B) in 48-hour light/dark  cycle measured by CLAMS  in M-SCT floxed and M-SCT  KO mice  with HFD  (n = 6 per group), dark  phase is marked as dark background. Regression-based absolute oxygen  consumption  (A) or  heat production (B) analysis of  body weight  are shown in the right part. Data information: Statistical significance was determined using Two-tailed Student's t test. Data in panel A and B have been analyzed using ANCOVA with oxygen consumption or heat production as dependent variable, group as fixed variable and body weight as covariate. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "C Body temperature  of 8-week-old M-SCT  floxed and M-SCT  KO male offspring with chow diet during cold  exposure (4℃; n = 8). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "D Representative HE staining  and UCP1 staining  of Ing  from M-SCT  floxed and M-SCT  KO mice  with chow diet maintained at RT  or 3 days of cold  exposure (4℃). Scale bar, 100 μm.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "E Relative mRNA levels of UCP1, CIDEA, PRDM16, PGC1α  and DIO2  in iWAT  from M-SCT  floxed and M-SCT  KO mice  with chow diet (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "CIDEA: 12683
DIO2: 13371
PGC1α: 19017
PRDM16: 70673
SCT: 319229
UCP1: 22227"
  },
  {
    "caption": "F Representative western blots  of UCP1, PRDM16, PGC1α and HSP90  in iWAT  from M-SCT  floxed and M-SCT  KO mice  with chow diet  after 3 days of cold  exposure (4℃). G Total UCP1  protein per mg iWAT  of M-SCT  floxed and M-SCT KO mice  with chow diet  maintained at RT  or exposed to cold  for 3 d (4℃) (n = 3). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "H Relative mRNA levels of UCP1, PGC1α, PRDM16, CIDEA  and DIO2  in SVF  isolated from M-SCT  KO and M-SCT  floxed mice with HFD (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "CIDEA: 12683
DIO2: 13371
PGC1α: 19017
PRDM16: 70673
SCT: 319229
UCP1: 22227"
  },
  {
    "caption": "I, J OCR  of Oligomycin, FCCP  and Antimycin A/Rotenone-treated matured adipocytes  derived from iWAT-SVF  of M-SCT  KO and M-SCT floxed mice  with HFD, and the AUC of OCR  as indicated were calculated (n = 5 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "K Glucose  oxidation in adipocytes  derived from iWAT-SVF  of M-SCT  KO and M-SCT  floxed mice  with HFD  (n = 8 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "B Stacked bars showing the Proportional distribution of hypo- and hypermethylated  DMRs  (M-SCT  KO vs M-SCT  floxed) in different regions. Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "C Heat map of DMR methylation  level in mRNA between M-SCT  floxed and M-SCT  KO. The color bar indicates the normalized tag counts in M-SCT  floxed or M-SCT  KO. Positive z scores, shown in the table, indicate hypermethylated regions, while negative z scores imply hypomethylated regions. D As in (C), for enhancer region.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "E Scatter plot representation of the most significant difference of methylation  in mRNA  (left) and enhancer  (right) regions between M-SCT  floxed and M-SCT  KO (p < 0.005). Data information: Statistical significance was determined using Two-tailed Student's t test.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "F Volcano plot  DNA methylation  represents all DMRs in mRNA  (left) and enhancer  (right) regions. Cutoffs (vertical and horizontal dashed lines) used to identify DMRs  between M-SCT  floxed and M-SCT  KO mice. The vertical lines correspond to twofold up and down, respectively, and the horizontal line represents a P value of 0.01. Data information: Statistical significance was determined using Two-tailed Student's t test.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "I, J Schematic diagram showing the CpG islands of Mus musculus PRDM16  (I) and CIDEA  (J) genes. The conditions to be met by CpG islands identified were: 200-300 bp length, CG content of > 50% and observed CpG content vs expected CpG content > 0.6. Methylation  levels of each CpG islands in PRDM16  (I) and CIDEA  (J) are presented as the fold change relative to the average value of the M-SCT  floxed group and β-actin promoter was used as a negative control (n = 3 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not statistically significant.",
    "ncbi_link": "β-actin: 11461
CIDEA: 12683
PRDM16: 70673
SCT: 319229"
  },
  {
    "caption": "A Western blots  analysis of DNMT1, DNMT3a, DNMT3b  and HSP90  in Ing  from M-SCT  KO and M-SCT floxed mice  with HFD.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "B Relative mRNA levels of DNMT1, DNMT3a  and DNMT3b  in Ing  from M-SCT  KO and M-SCT  floxed mice  with HFD  (n = 8). Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. ns, not statistically significant.",
    "ncbi_link": "DNMT1: 13433
DNMT3a: 13435
DNMT3b: 13436
SCT: 319229"
  },
  {
    "caption": "C Western blots analysis of p-AMPKα, AMPKα, p-ACC, ACC, DNMT1  and HSP90  in embryo  of M-SCT  KO and M-SCT  floxed mice  at E18.5.",
    "ncbi_link": "SCT: 319229"
  },
  {
    "caption": "G Western blot  analysis of p-AMPKα, AMPKα, p-ACC, ACC, DNMT1  and HSP90  in AMPK+/+ or AMPKα1/α2  double knockout (AMPK-/-) MEF  cells treated with 10 nM SCT  for 24 h.",
    "ncbi_link": "AMPK: 105787
AMPKα1: 105787
α2: 108079"
  },
  {
    "caption": "H, I Western blot analysis of Flag-DNMT1  in Flag-DNMT1-transfected HEK293T  cells treated with AICAR  with indicated dose or time  periods.",
    "ncbi_link": "Flag: 
DNMT1: 1786"
  },
  {
    "caption": "L AMPK+/+ or AMPK-/- MEF  cells were transfected with indicated plasmids and then lysed, followed by IP  and IB  analysis.",
    "ncbi_link": "AMPK: 105787"
  },
  {
    "caption": "I Relative mRNA levels of UCP1, PGC1α, PRDM16, CIDEA  and DIO2  in iWAT  from M-HFD  and M-HFD+SCT mice  with HFD  (n = 5 per group). Data information: Statistical significance was determined using Two-tailed Student's t test. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "CIDEA: 12683
DIO2: 13371
PGC1α: 19017
PRDM16: 70673
UCP1: 22227"
  },
  {
    "caption": "(D, E) representative confocal micrographs and quantification of LC3-II accumulation in CTNSWT and CTNS-/- cells in presence and absence of 25 nM bafilomycin (BafA1) for 4 hrs, respectively (n = 3). Scale bars are 20 µm.",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(F, G, H) Western blotting and densitometric analyses for LC3-II/LC3-I ratio and SQSTM1 protein levels in CTNSWT, CTNS-/-, and CTNSPatient cells cultured in the presence or in the absence of 25 nM BafA1 for 4 h, respectively (n = 3).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(I, J) Representative confocal micrographs and quantification of DQ-BSA and BSA in CTNSWT, CTNS-/-, and CTNSPatient cells, respectively (n = 7-14 quantified images). Scale bars are 20 µm.",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(D) List of metabolites that were shared and significantly altered in both the CTNS-/- and CTNSPatient cells compared to control cells (n = 6).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(I) List of proteins that were significantly upregulated and downregulated in CTNS-/- cells compared to control cells (n = 3). AKGDH; Alpha-ketoglutarate dehydrogenase, LIPA; Lysosomal acid lipase, ACP2; Lysosomal acid phosphatase, CTSS; Cathepsin S, CTSC; Dipeptidyl peptidase, IGF2R; Cation-independent mannose-6-phosphate receptor, SORT1; Sortilin, CAT; Catalase, CTSA; Lysosomal protective protein, and SOD; Superoxide dismutase.",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(B, C, D) ROS production (ROS/mg protein) in CTNSWT, CTNS‑/-, and CTNSPatient cells upon starvation for 4 hrs in the presence and absence of DMKG (4 hrs), respectively (n = 3).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "Representative confocal micrographs (scale bars are 20 µm) of caspase 3/7 activation in DMKG (2 mM)-treated CTNSWT, CTNS‑/-, and CTNSPatient cells for 24 hrs (n = 3).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(H, I) Western blotting and densitometric analyses for LC3-II/LC3-I ratio in CTNSWT, CTNS‑/-, and CTNSPatient cells cultured in the presence or in the absence of BafA1 (25 nM) and DMKG (2 mM) for 4 hrs, respectively (n = 3).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(E), Proteomic analysis of CTNS-/- cells treated with cysteamine, bicalutamide, and a combination of cysteamine and bicalutamide, respectively (n = 3). AKGDH; Alpha-ketoglutarate dehydrogenase, GLUD1; GLUD2; Mitochondrial glutamate dehydrogenase 1/2, IGF2R; Cation-independent mannose-6-phosphate receptor, GSTK1; Glutathione S-transferase kappa 1, COX6B1; Cytochrome c oxidase subunit 6B1, ACACA; Acetyl-CoA carboxylase 1-Biotin carboxylase, GLS; Glutaminase kidney isoform, mitochondrial, CASP3; Caspase-3, NPC1; Niemann-Pick C1 protein.",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(D, E) Representative confocal micrographs and quantification of DQ-BSA in CTNSWT, and CTNS-/- cells upon treatment with bicalutamide. Scale bars are 20 µm (n = 8-14 quantified images).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(F) Quantification of cystine levels (nmol/mg protein) by HPLC-MS/MS in CTNS-/- in the absence of the drug (NT) (n = 4) or upon treatment with cysteamine (n = 6), bicalutamide (n = 6), and a combination of cysteamine and bicalutamide (n = 6). (G) Quantification of cystine levels (nmol/mg protein) by HPLC-MS/MS in CTNSPatient in the absence of the drug (NT) (n = 4) or upon treatment with cysteamine (n = 4), bicalutamide (n = 4), and a combination of cysteamine and bicalutamide (n = 6).",
    "ncbi_link": "CTNS: 1497"
  },
  {
    "caption": "(A) Immunocytochemistry of patient-derived cystinotic tubuloids (CNTSPatient-1 and CTNSPatient-2) and healthy kidney tissue-derived control tubuloids (CNTSWT-1 and CTNSWT-2) for PAX8, TP63 and F-actin. Scale bar = 100 µm.",
    "ncbi_link": "CNTS: 1497
CTNS: 1497"
  },
  {
    "caption": "(C, D) Quantification of cystine levels (nmol/mg protein) by HPLC-MS/MS in two different patient-derived cystinotic tubuloids in the absence of the drugs (NT) or upon treatment with cysteamine (100 μM), bicalutamide (35 μM) or cysteamine (100 μM)-bicalutamide (35 μM) combination treatment (n = 3). (E) αKG levels measured in patient-derived cystinotic tubuloids (CNTSPatient-1 and CTNSPatient-2) in the absence of the drugs (NT) or upon treatment with cysteamine, bicalutamide or cysteamine-bicalutamide combination treatment using metabolomics (n = 3). ",
    "ncbi_link": "CNTS: 1497
CTNS: 1497"
  },
  {
    "caption": "(I) Survival rates in ctns-/- zebrafish upon treatment with cysteamine, bicalutamide, and a combination of cysteamine and bicalutamide (n=40 embryos per group).",
    "ncbi_link": "ctns: 553594"
  },
  {
    "caption": "(K) Hatching rates in surviving ctns-/- zebrafish evaluated at 72 and 96 hrs post fertilization (hpf) with cysteamine, bicalutamide, and a combination of cysteamine and bicalutamide (n=40 embryos per group).",
    "ncbi_link": "ctns: 553594"
  },
  {
    "caption": "(A-B) THP1 over-expressing IFITM3, IFITM3-Y20F, IFITM3-∆21 or control were pre-treated or not with Amphotericin B for 1 hour and then transduced with a VSV-gp (A) or Measles-gp (B) pseudotyped LV. Transduction efficiencies were evaluated at FACS five days later. Fold rescue of transduction over the DMSO control was calculated. Data are shown as mean ± SEM (n=5-8 biological replicates run in technical duplicate). P values are for one sample t test versus Oe-Luc DMSO =1, ** for p<0.01, *** for p<0.001.",
    "ncbi_link": "gp: 
Luc: 
IFITM3: 10410
gp: 1489834"
  },
  {
    "caption": "(E-F) THP1 over-expressing IFITM3, IFITM3 lysin-less mutant (4KR) (E), IFITM3 CIL-lysin mutant (3KR) (F) or control were transduced with VSV-gp pseudotyped LV. Transduction efficiencies were evaluated by flow cytometry five days post-TD. Data represent the mean ± SEM (n=9-6 biological replicates run in technical duplicate). p values are for one sample t test verso Oe-Luc DMSO= 1. * for p<0.05 ** for p<0.01. **** for p<0.0001 and ns for not significant.",
    "ncbi_link": "Luc: 
IFITM3: 10410
gp: 1489834"
  },
  {
    "caption": "(G-H) THP1 over-expressing IFITM1, IFITM1-3KR (G), IFITM3, IFITM3-Y20F, IFITM3-Y20F-3KR (H) or control were transduced with Measles-gp pseudotyped LV. Transduction efficiencies were evaluated by flow cytometry five days post-TD. Data represent the mean ± SEM (n=4-9 biological replicates run in technical duplicate). p values are for one sample t test verso Oe-Luc DMSO= 1. * for p<0.05 ** for p<0.01.**** for p<0.0001.",
    "ncbi_link": "gp: 
Luc: 
IFITM1: 8519
IFITM3: 10410"
  },
  {
    "caption": "(A-B) Immunofluorescence images were performed using TCS SP5 Leica confocal microscope, 60x with oil on THP1 over-expressing IFITM3-WT, IFITM3-4KR, IFITM3-3KR or IFITM3-Y20F (A) (n=22 images acquired from 3 biological replicates) and primary monocytes derived macrophages (MDM) over-expressing IFITM3-WT, IFITM3-4KR, IFITM3-3KR (B) (n=12 images acquired from 3 independent donors). Co-localization (purple areas marked by white arrows) of IFITM3 (in red) with the lysosome associated membrane protein 1 (LAMP1) marker (in blue) was evaluated. Representative zoomed images are shown,",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(D) IFITM3-IFITM3 interactions (red dots) were evaluated by proximity ligation assay (PLA) in THP1 knock out for endogenous IFITM3 and expressing either HA-IFITM3 and His-IFITM3, HA-3KR and His-3KR or His-dimer mutant IFITM3 (D.M) and HA-dimer mutant. Images were acquired on TCS SP5 Leica confocal microscope 60x with oil. Representative images are shown (n=8 images of 4 biological replicates), scale bar 40μm.",
    "ncbi_link": "HA: 
His: 
IFITM3: 10410"
  },
  {
    "caption": "(B) K562 were prestimulated with IFNα and then transduced with VSV-gp pseudotyped LV. Transduction was evaluated five days after TD (mean ± SEM, n=4 biological replicates run in technical duplicate). Data are represented as Folds over the Oe-Luc control. p values are for one sample t test versus -IFNα = 1. ns for not significant.",
    "ncbi_link": "Luc: 
gp: 1489834"
  },
  {
    "caption": "(F) K562 over-expressing IFITM1, IFITM1-3KR or control were transduced with Measles-gp pseudotyped LV. Transduction efficiency was evaluated five days post-TD (mean ± SEM, n=4 biological replicates run in technical duplicate). p values are for one sample t test versus Oe-Luc = 1. **** for p<0.0001.",
    "ncbi_link": "gp: 
Luc: 
IFITM1: 8519"
  },
  {
    "caption": "K562 over-expressing IFITM3, IFITM3-Y20F, IFITM3-Y20F-3KR or control were pre-exposed or not to Ampho B and then transduced with Measles-gp (G), BaEV-gp (H) pseudotyped LV. Transduction efficiencies were measured by flow cytometry five days after TD (mean ± SEM, n=5-4-4 biological replicates run in technical duplicate). p values are for one sample t test versus Oe-Luc DMSO=1 or unpaired t test for Ampho B versus DMSO. * for p<0.05, ** for p<0.01, *** for p<0.001, **** for p<0.0001.",
    "ncbi_link": "gp: 
Luc: 
gp: 22318530
IFITM3: 10410"
  },
  {
    "caption": "(A) Interaction between IFITM3 wild-type or 3KR and Phosphatydinositol-3 phosphate (PIP3) (red dots) was evaluated by proximity ligation assay. Images were acquired using TCS SP5 Leica confocal microscope 60x with oil in THP1 knock out for endogenous IFITM3 and expressing either IFITM3 wild-type or IFITM3-3KR. Number of foci were counted on imageJ and normalized over the number of nuclei (mean ± SEM, n=5 biological replicates). White arrows indicate foci, scale bar 40μm.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(B) Phosphatydinositol-3 phosphate (PIP3) levels were measured by immunofluorescence in THP1 over-expressing the His-IFITM3/HA-IFITM3 and His-3KR/HA-3KR. PIP3 was quantified via Imagej (mean ± SEM, n=5 biological replicates).",
    "ncbi_link": "HA: 
His: 
IFITM3: 10410"
  },
  {
    "caption": "(C) THP1 over-expressing IFITM3 or control were transduced with VSV-gp pseudotyped LV in presence or absence of Rapamycin (Rapa). Transduction efficiency was measured at FACS five days post-TD (mean ± SEM, n=6 biological replicates run in technical duplicate. p values are for one sample t test versus Oe-Luc DMSO=1 and Mann Whitney test for Rapa vs DMSO. ** for p<0.01, **** for p<0.0001.",
    "ncbi_link": "Luc: 
IFITM3: 10410
gp: 1489834"
  },
  {
    "caption": "(D) THP1 over-expressing IFITM3-Y20F-3KR or control were exposed or not to Rapamycin and transduced with Measles-gp pseudotyped LV. Transduction efficiency was evaluated by flow cytometry five days post-TD (mean ± SEM, n=4 biological replicates run in technical duplicate). p values are for one sample t test versus Oe-Luc DMSO=1. ** for p<0.0.",
    "ncbi_link": "gp: 
Luc: 
IFITM3: 10410"
  },
  {
    "caption": "(E) Hematopoietic stem and progenitor cells (HSPC) were transduced with VSV-gp or Measles-gp pseudotyped LV in presence or absence of Rapamycin. Transduction was evaluated at FACS five days later measuring the % of BFP expression (mean ± SEM, n=4 biological replicates run in technical duplicate). p values are for Mann Whitney test. * for p<0.05.",
    "ncbi_link": "gp: 
gp: 1489834"
  },
  {
    "caption": "(E) PIP3 levels were measured by immunofluorescence (scale bar 40μm) and quantified as integrated density with ImageJ software in THP1 and K562 over-expressing IFITM3 (mean ± SEM, n=3 biological replicates). p values are for Mann Whitney test, * for p<0.05.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(A) Calu3 over-expressing IFITM1, IFITM2, IFITM3, PM-mutant IFITM3 Y20A or control were transduced with SARS-CoV2 Spike-pseudotyped LV (mean ± SEM, n>6 biological replicates run in technical duplicate). Transduction efficiency was measured by FACS five days after transduction, p values are for one sample paired T test versus Oe-Luc Ctrl=1, **for p<0.01.",
    "ncbi_link": "Luc: 
IFITM1: 8519
IFITM2: 10581
IFITM3: 10410
Spike: 43740568"
  },
  {
    "caption": "(B-C) Calu3 cells over-expressing IFITM1, IFITM2, IFITM3, IFITM3 Y20A or control were infected with SARS-CoV2. Viral titer was calculated by plaque assay in Vero E6 cells (mean ± SEM, n=4 biological replicates run in technical duplicate). p values are for Mann Whitney test, * for p<0.05, *** for p<0.001.",
    "ncbi_link": "IFITM1: 8519
IFITM2: 10581
IFITM3: 10410"
  },
  {
    "caption": "(G) Calu3 over-expressing IFITM1, IFITM3 or control were challenged to SARS-CoV2 Omicron pseudotyped LV. Transduction efficiency was evaluated 5 days post-transduction (mean ± SEM, n=7 biological replicates run in technical duplicate). p values are for one sample T test versus Oe-Luc Ctrl=1, **for p<0.01, ****for p<0.0001.",
    "ncbi_link": "Luc: 
IFITM1: 8519
IFITM3: 10410"
  },
  {
    "caption": "(H-I) Calu3 cells over-expressing IFITM1, IFITM2, IFITM3 or control (H) or IFITM3, Y20A or control (I) were infected with Omicron at MOI 1. Viral supernatants were collected at different time points and tittered on Vero E6 cells. Data are presented as mean ± SEM (n=4-4 biological replicates run in technical triplicate). p values are for Mann Whitney test , **for p<0.01, ***for p<0.001, ****for p<0.0001.",
    "ncbi_link": "IFITM1: 8519
IFITM2: 10581
IFITM3: 10410"
  },
  {
    "caption": "(A-B) VSV (A) or ZIKV (B) viral supernatants were collected one day post-infection in THP1 (A) or Calu3 (B) over-expressing IFITM3, IFITM3 lysin-less mutant (4KR), IFITM3 CIL-lysin mutant (3KR) or control and titered on VERO E6 cells. Data represent the mean ± SEM (n=5-3 biological replicates run in technical duplicate). p values are for Mann Whitney test. * for p<0.05, ** for p<0.01.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(I) IFITM3 and PIP3 level were measured by immunofluorescence (scale bar 100µm) and quantified as integrated density with ImageJ software in Calu3 infected or not with Omicron (n=3 biological replicates). p values are for Mann Whitney test, ** for p<0.01. (J) PIP3 coupled to a specific PIP carrier (PIP3+Carr Ctrl) or Carr Ctrl were provided to Calu3 over-expressing IFITM3, control or KO for IFITM3 prior to infection with SARS-CoV2 Omicron. Infectious supernatants were collected after three days and tittered in Vero E6 cells (mean ± SEM, n=4 biological replicates run in technical duplicate ). p values are for Wilcoxon signed ranked test, * for p<0.05. The inhibitory effect of exogenous PIP3 on infection is represented as Fold versus Carr Ctrl (mean ± SEM, n=4 biological replicates run in technical duplicate ). p values are for Mann Whitney test, * for p<0.05.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "B HXT2 mRNA localization correlate with that of the protein. FISH with an HXT2-specific probe. Early in the cell cycle the mRNA is predominantly found in the mother cell (white arrowheads) while it is equally distributed after meta-to-anaphase transition (MAT) (yellow arrowheads). C Quantification of (B). The fluorescence intensities from mother and bud were independently measured and the ratio of the signal from the mother over the signal from the bud was calculated. Values > 1 indicate a stronger signal in the mother, < 1 a stronger signal in the bud and around 1 equal distribution. Three independent experiments with 50 mother cells and 50 buds per experiment were analyzed. Boxes represent the interquartile range from the 25th to the 75th percentile with the median. Whiskers represent the 10th and 90th percentile, respectively. ",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "D Changes of HXT2 mRNA localization appear to be independent of the cytoskeleton. Cells were either treated for 15 min with 30 mg/ml latrunculin A or with 30 mg/ml benomyl. White arrowheads point to small-budded and yellow arrowheads to large budded cells. E Quantification of (D) of three in dependent experiments with at least 50 cells each. Values > 1 indicate a stronger signal in the mother, < 1 a stronger signal in the bud and around 1 equal distribution. Boxes represent the interquartile range from the 25th to the 75th percentile with the median. Whiskers represent the 10th and 90th percentile, respectively. ",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "A, Inhibiting translation by either applying Cycloheximide (CHX) or Verrucarin A (VerruA) leads to the retention of HXT2 mRNA in the mother cell after MAT. Chloro: chloroform; solvent control for VerruA; NT: not treated; control for CHX.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "C CHX treatment leads to increased transcript stability. Quantitative PCR of HXT2 mRNA in CHX-treated cells in comparison to prt1-1 mutant cells. The data represents 3 independent experiments and the standard deviation is given.",
    "ncbi_link": "HXT2: 855023
prt1-1: 854543"
  },
  {
    "caption": "D Translation of HXT2 mRNA is more active late in the cell cycle. The HXT2 mRNA level bound to either di-/trisomes and polysomes (≥ 4 ribosomes) over monosomes was determined by extraction of mRNA from cells elutriated and harvested at G1/S or M-phase followed by qPCR. At G1/S similar levels of the HXT2 mRNA were found in the different ribosome fractions, whereas in M-phase more mRNA was bound to polysomes, suggesting a more active translation in M-phase.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "E The localization of HXT2 mRNA is independent of the Signal Recognition Particle (SRP). Deletion of SRP54 does not affect the retention in the mother cell or the equal distribution of HXT2 mRNA.",
    "ncbi_link": "HXT2: 855023
SRP54: 856203"
  },
  {
    "caption": "A Deletion of SCP160, ASC1, or BFR1 increases HXT2 mRNA signal in the bud. FISH experiment with deletions in various RNA binding proteins.",
    "ncbi_link": "ASC1: 855143
BFR1: 854373
HXT2: 855023
SCP160: 853365"
  },
  {
    "caption": "B The effect of ∆scp160 on HXT2 mRNA localization is independent of its increased ploidy. Scp160 truncations that lack either the last two (∆C2) or the last four (∆C4) KH domains or a Tet-off SCP160 construct, in which expression is blocked by the addition of doxycycline (Doxy)",
    "ncbi_link": "HXT2: 855023
SCP160: 853365
scp160: 853365
Scp160: 853365"
  },
  {
    "caption": "D Hyperactivation of PKA drives accumulation of HXT2 mRNA in the bud. Treatment of cells with forskolin (+Forsko) or using a ∆bcy1 strain, causes HXT2 mRNA to be bud-enriched.",
    "ncbi_link": "bcy1: 854778
HXT2: 855023"
  },
  {
    "caption": "E HXT2 mRNA enrichment upon refeeding is Ras2-dependent.",
    "ncbi_link": "HXT2: 855023
Ras2: 855625"
  },
  {
    "caption": "A Table of the glucose affinity of the four most important hexose transporters. B FISH of HXT1, 3 and 4 under glucose rich conditions. White arrowheads depict cells before, yellow arrowheads cells after MAT. C Quantification of (B). ",
    "ncbi_link": "HXT1: 856494"
  },
  {
    "caption": "E HXT2 mRNA is the only HXT mRNA showing enrichment in the bud after MAT upon transient PKA activation.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "F Elutriation confirms enrichment of HXT2 mRNA in daughter cells upon refeeding. Daughters and mothers were separated through elutriation. qPCR was performed to determine the relative levels of different HXTs and ASH1 mRNA in both fractions.",
    "ncbi_link": "ASH1: 853650
HXT2: 855023"
  },
  {
    "caption": "G Enrichment of HXT2 mRNA in the bud leads to higher Hxt2-GFP transporter levels at the plasma membrane of the daughter cells. Daughter cells were enriched through elutriation. Quantification of the fluorescence intensity of the plasma membrane from life cell imaging from three independent experiments in which at least 50 cells were analyzed per condition and experiment. Western blot analysis confirms the higher amount of Hxt2-GFP transporter protein present in daughter cells under glucose-shift conditions",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "A RNA degradation is not essential for asymmetric HXT2 mRNA localization. FISH of wild-type and ∆xrn1 cells.",
    "ncbi_link": "HXT2: 855023
xrn1: 852702"
  },
  {
    "caption": "B The cytoskeleton contributes to HXT2 mRNA enrichment in the bud. Cells were treated upon glucose addition with either 120 mg/ml benomyl for 15 min, 30 mg/ml latrunculin A for 30 min or 200 µM CK-666 for 30 min. HXT2 mRNA was detect by FISH.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "C Asymmetric loading of HXT2 mRNA onto the nuclear envelope and enrichment in the bud requires Kar9 but not Bim1 function. HXT2 mRNA FISH with ∆bim1 and ∆kar9 strains. Arrows point to a nucleus with HXT2 signal. D Quantification of the daughter cell enrichment from data displayed in (C). E Quantification of the HXT2 mRNA signal in cells with two nuclei in the mother cell from the experiment depicted in (C). Percentage of cells with asymmetric HXT2 mRNA staining is displayed. ",
    "ncbi_link": "bim1: 856736
HXT2: 855023
kar9: 855859"
  },
  {
    "caption": "A Deletion of NUP2 and MLP1/2 reduced HXT2 mRNA enrichment in the bud. FISH under glucose shift conditions with strains in which different NPC components were deleted. B Quantification of (A). ",
    "ncbi_link": "HXT2: 855023
MLP1: 853970
NUP2: 851048"
  },
  {
    "caption": "C HXT2 mRNA is on the nuclear envelope after MAT upon glucose shift. FISH-IF experiment with a probe against HXT2 mRNA and an antibody against the HA tag of the nuclear pore complex component Nup84-HA. White arrows point to HXT2 mRNA signals on the nuclear envelope.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "D HXT2 mRNA travels on the nuclear envelope into the bud during mitosis after glucose shift. Stills of time lapse movies. HXT2 mRNA was visualized using the MS2-GFP system. Under glucose shift conditions HXT2 mRNA is mostly localized to the bud together with the nucleus. Under glucose rich conditions HXT2 mRNA moves mostly independent of the nucleus. Cyan: Nup84-mCherry; white arrowhead: HXT2 mRNA-MS2 + MCP-GFP.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "HXT2 only strains grow faster than the other HXT only strain. Growth was assessed 2-3 days after incubation at 30°C.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "D Quantification of competition assay. qPCR with primers against either HXT1, 2, 3 or 4 was performed. HXT gene abundance was normalized against actin.",
    "ncbi_link": "actin: 
HXT1: 856494"
  },
  {
    "caption": "E Strains that lack HXT2 grow slower when coming from quiescence compared to WT.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "F Tagging the HXT2 mRNA with U1A stem loops leads to its artificial enrichment in the bud in 96% of cells independently of the cell cycle. Arrows point to examples of HXT2-U1A mRNA in the bud early and late in the cell cycle.",
    "ncbi_link": "U1A: 
HXT2: 855023"
  },
  {
    "caption": "G Cells that always enrich HXT2 mRNA in the bud have a growth advantage in the first hours when coming from quiescence compared to WT or cells that only express HXT2.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "H Daughter cells do not retain a memory of the previous stress situation encountered by their mothers. Cells were re-fed after starvation and analyzed for enrichment of HXT2 mRNA via FISH at different time points.",
    "ncbi_link": "HXT2: 855023"
  },
  {
    "caption": "(a) MEFs stably expressing EGFP-tagged wild-type (WT) or T240R mutant forms of Parkin as well as FLAG-tagged VAP-A were incubated in the absence or presence of CCCP (30 μM) for 24 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to FKBP38, to FLAG (M2) and to cytochrome c. The fluorescence of EGFP was also monitored directly.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "(b) MEFs stably expressing FLAG-Parkin and EGFP-tagged forms of FKBP38, Omp25, Omp25/FKBP38 or FKBP38/Omp25 were treated with CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to cytochrome c and to FLAG (rabbit polyclonal). The fluorescence of EGFP was also monitored directly. Scale bar, 10 μm.",
    "ncbi_link": "FKBP38: 14232
Omp25: 24071"
  },
  {
    "caption": "(c) MEFs stably expressing mCherry-tagged Parkin and EGFP-tagged forms of FKBP38, Omp25, Omp25/FKBP38 or FKBP38/Omp25 were incubated in the absence or presence of CCCP (30 μM) for 24 h and then subjected to immunoblot analysis.",
    "ncbi_link": "FKBP38: 14232
Omp25: 24071"
  },
  {
    "caption": "(a) MEFs stably expressing FLAG-Parkin and either EGFP-Bcl-2 or EGFP-Bcl-xL were incubated in the absence or presence of CCCP (30 μM) for 24 h and then subjected to immunoblot analysis.",
    "ncbi_link": "Bcl-2: 12043
Bcl-xL: 12048"
  },
  {
    "caption": "(c) MEFs stably expressing FLAG-Parkin and EGFP-tagged forms of Bcl-2, Bcl-xL, Bcl-2/xL or Bcl-xL/2 were incubated in the absence or presence of CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to cytochrome c and to FLAG (rabbit polyclonal). The fluorescence of EGFP was also monitored directly. (d) Higher-magnification views of the boxed areas in c. Scale bar (c,d), 10 μm.",
    "ncbi_link": "Bcl-2: 12043
Bcl-xL,: 12048"
  },
  {
    "caption": "(a) MEFs stably expressing EGFP-FKBP38(N402K) and FLAG-Parkin were incubated in the absence or presence of CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to cytochrome c and to FLAG (rabbit polyclonal). The fluorescence of EGFP-FKBP38(N402K) was also monitored directly. Higher-magnification views of the boxed areas are shown in the right panels of each set.",
    "ncbi_link": "FKBP38: 14232"
  },
  {
    "caption": "(b) MEFs stably expressing EGFP-FKBP38(N402K), mCherry-FKBP38 and FLAG-Parkin were incubated in the absence or presence of CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to FLAG (M2). The fluorescence of EGFP-FKBP38(N402K) and mCherry-FKBP38 was also monitored directly.",
    "ncbi_link": "FKBP38: 14232"
  },
  {
    "caption": "(c) MEFs stably expressing FLAG-Parkin and either EGFP-FKBP38 or EGFP-FKBP38(N402K) were incubated in the absence or presence of CCCP (30 μM) for 24 h and then subjected to immunoblot analysis. (d) Densitometric quantitation of EGFP fusion protein abundance in immunoblots similar to those in (c). Data are expressed relative to the corresponding control value (CCCP 0 h) and are means±s.d., from three independent experiments. **P0.01 (Student's t test).",
    "ncbi_link": "FKBP38: 14232"
  },
  {
    "caption": "(e) MEFs stably expressing EGFP-Bcl-2(H235R) and FLAG-Parkin were incubated in the absence or presence of CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to cytochrome c and to FLAG (rabbit polyclonal). The fluorescence of EGFP-Bcl-2(H235R) was also monitored directly. Higher-magnification views of the boxed areas are shown in the right panels of each set.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(g) HeLa cells stably expressing FLAG-Parkin were transiently transfected with vectors for KikGR-FKBP38ΔN47 or KikGR-FKBP38ΔN47(N402K), exposed to UV, incubated in the absence or presence of CCCP (10 μM) for 4 h, and then monitored for red and green KikGR fluorescence. Scale bar (a,b,e,g), 10 μm.",
    "ncbi_link": "FKBP38: 23770
Parkin: 5071"
  },
  {
    "caption": "(a) Wild-type (Mfn2+/+) and Mfn2 knockout (Mfn2-/-) MEFs stably expressing mCherry-Parkin were incubated in the absence or presence of CCCP (30 μM) for 4 h, fixed, permeabilized and subjected to immunofluorescence analysis with antibodies to FKBP38 and to cytochrome c. The fluorescence of mCherry-Parkin was also monitored directly.",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(f) Wild-type (Fkbp38+/+) and Fkbp38 knockout (Fkbp38−/−) MEFs stably expressing FLAG-Parkin and either EGFP or EGFP-FKBP38 were incubated in the absence or presence of CCCP (30 μM) for 24 h and then stained with allophycocyanin (APC)-labelled annexin V and propidium iodide (PI) for flow cytometric analysis of the percentage of apoptotic cells (annexin V+ and PI+ cells). Data are means±s.d., from three independent experiments.",
    "ncbi_link": "Fkbp38: 14232
FKBP38: 14232
Parkin: 50873"
  },
  {
    "caption": "PTPδ-tdTomato protein is detected in tau-positive axonal compartments, but not in MAP2-positive dendritic compartments in cultured neurons (entorhinal cortex + hippocampus; 1:2 mixture; days in vitro or DIV 24) derived from Ptprd-/- mouse embryos. Note that the tdTomato signals envelop, but not overlap with, MAP2-delineated dendrites, although this does not necessarily suggest that tdTomato signals not in dendrites. Scale bars, 10 μm in main images and 2 μm in enlarged images.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Presynaptic PTPδ-tdTomato clusters colocalize more strongly with PSD-95 clusters (excitatory postsynaptic marker) relative to gephyrin (inhibitory postsynaptic marker) clusters in cultured neurons (entorhinal cortex + hippocampus; DIV24) derived from Ptprd-/- mouse embryos. See Fig EV1F for the quantification of the results. Scale bars, 10 μm in main images and 2 μm in enlarged images.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Gene dose-dependent reductions in PTPδ protein levels in whole brains of Ptprd+/- (HT) and Ptprd-/- (KO) mice relative to Ptprd+/+ (WT) mice (P21), shown by immunoblot analyses. Note that the C-terminal antibody also detects a non-specific band of similar size indicated by an asterisk, possibly either PTPσ or LAR.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Suppressed basal excitatory synaptic transmission in the Ptprd-/- hippocampal SLM layer, but not SO or SR layer (2 months; male), as shown by the I/O ratio (n = 14 slices from 5 mice [WT-SO], 14, 5 [KO-SO], 11, 4 [WT-SR], 12, 5 [KO-SR], 14, 6 [WT-SLM], 12, 6 [KO-SLM], mean ± SEM, *p < 0.05; **p < 0.01, two-way repeated-measures/RM ANOVA, Holm-Sidak post-hoc multiple comparisons test). (F, H, and J) Normal presynaptic release in the Ptprd-/- hippocampal SLM, SO, and SR layers (P22-27; male), as shown by the PPF ratio (n = 13 slices from 5 mice [WT-SO], 13, 5 [KO-SO], 10,4 [WT-SR], 12, 5 [KO-SR], 15, 6 [WT-SLM], 14, 6 [KO-SLM], mean ± SEM, ns, not significant, two-way RM ANOVA).",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Decreased PSD density, but not PSD length, thickness, or perforation (%), in the Ptprd-/- SLM (P21; male), revealed by EM. Arrows in panel K indicate PSDs.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Decreased PSD density, but not PSD length, thickness, or perforation (%), in the Ptprd-/- SLM (P21; male), revealed by EM. Arrows in panel K indicate PSDs. (n = 18 images from 3 mice [WT and KO], ***p < 0.001, ns, not significant, Student's t-test for L, O-R, Mann-Whitney U test for M, N). Scale bar, 500 nm.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Decreased density of presynaptic nerve terminals but normal area of nerve terminals and normal density of presynaptic vesicles in the Ptprd-/- SLM (P21; male), revealed by EM. (n = 3 mice [WT and KO], mean ± SEM, ***p < 0.001, ns, not significant, Student's t-test).",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "A volcano plot of proteins that showed significant up- or downregulation of pTyr levels (absolute fold change > 1.5, p < 0.05) in the whole brain of Ptprd-/- mice (P21). Note that IL1RAPL1 is the protein with the strongest decrease in pTyr levels. (n = 3 for WT and 3 for KO). See Dataset EV1, 'Phosphoscan Results' tab for a full list of significantly changed proteins.",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Decreased pTyr levels, but normal total levels of IL1RAPL1 protein, in the Ptprd-/- brain (P21-27), as revealed by immunoprecipitation of IL1RAPL1 from whole-brain lysates followed by immunoblotting for total IL1RAPL1 protein and pTyr levels (4G10 antibody).",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Decreased levels of synaptic IL1RAPL1 protein in the Ptprd-/- brain (P21-27), as revealed by immunoblotting of crude synaptosomal (P2), synaptic plasma membrane (SPM), and PSD (PSD II) fractions. Analysis of immunoblots reveal significant decrease of IL1RAPL1 in the SPM and PSD fractions of Ptprd-/- brain samples. (n = 3 mice [WT and KO] for each fraction [P2, SPM, and PSD], mean ± SEM, **p<0.01, Student's t-test).",
    "ncbi_link": "Ptprd: 19266"
  },
  {
    "caption": "Normal levels of the PTPδ protein in whole-brain lysates of Ptprd-meA-/- mice (P21-27), which contrasts with the Ptprd-/- brain, where PTPδ protein is undetectable.",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Strongly decreased levels of tyrosine-phosphorylated PTPδ protein in whole-brain lysates of Ptprd-meA-/- mice (P21-27), as shown by the immunoprecipitation of IL1RAPL1 protein from whole-brain lysates followed by immunoblotting for total and tyrosine-phosphorylated PTPδ protein.",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Decreased levels of synaptic IL1RAPL1 protein in the Ptprd-meA-/- brain (P21-27), as revealed by immunoblotting P2, SPM, and PSD (PSD II) fractions. Analysis of immunoblots reveal significant decrease of IL1RAPL1 in the SPM and PSD fractions of Ptprd-meA-/- brain samples. (n = 3 mice [Ptprd-meA+/+ and Ptprd-meA-/-] and [P2, SPM, and PSD], mean ± SEM, *p<0.05, ***p < 0.001, Student's t-test). Note that, while unchanged in the P2 and SPM fractions, PTPδ is significantly decreased in the PSD of Ptprd-meA-/- samples.",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Decreased basal excitatory synaptic transmission in the hippocampal SLM region of Ptprd-meA-/- mice, as shown by the I/O ratio at the TA-SLM pathway (P20-24). (n = 15 slice from 5 mice [Ptprd-meA+/+], 12, 4 [Ptprd-meA-/-], mean ± SEM, *p < 0.05; ***p<0.001, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Normal presynaptic release in the hippocampal SLM region of Ptprd-meA-/- mice, as shown by the PPF ratio at the TA-SLM pathway (P20-24). (n = 15 slice from 5 mice [Ptprd-meA+/+] and 13, 4 [Ptprd-meA-/-], mean ± SEM, ns, not significant, two-way RM ANOVA).",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Hyperactivity of Ptprd-/- mice (2.5-4 months) in Laboras cages observed during light-off and light-on periods were strongly mimicked by Emx1-cKO mice, but more weakly by Viaat-cKO mice and not at all by Camk2a-cKO mice. Note also that immobility, a measure that better reflects sleep behavior, showed similar changes among different mouse lines. (n = 14 mice [WT], 14 [global KO], 16 [Emx1-cWT], 16 [Emx1-cKO], 11 [Viaat-cWT], 13 [Viaat-cKO], 18 [Camk2a-cWT] and 13 [Camk2a-cKO], mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001; ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "Camk2a: 12322
Emx1: 13796
Ptprd: 19266
Viaat: 22348"
  },
  {
    "caption": "Hyperactive behavior and decreased immobility of Ptprd-meA-/- mice (2.5-4 months) in Laboras cages observed during light-off periods and light-on periods, similar to Ptprd-/- mice. (n = 7 mice for Ptprd-meA+/+ and 7 mice for Ptprd-meA-/-, mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Increased WAKE duration and decreased NREM duration during the first three hours of the light-on period in Emx1-Cre;Ptprdfl/fl mice (2.5-4 months). (n = 9 mice [Emx1-cWT] and 9 mice [Emx1-cKO], mean ± SEM, *p < 0.05, **p < 0.01, ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "Cre: 2777477
Emx1: 13796
Ptprd: 19266"
  },
  {
    "caption": "Decreased delta power (normalized to total power) in NREM, but not WAKE, oscillations in Emx1-Cre;Ptprdfl/fl mice (2.5-4 months). Note also the normal theta power (normalized to total power) in REM oscillations in Emx1-Cre;Ptprdfl/fl mice. (n = 9 [Emx1-cWT] and 9 [Emx1-cKO], mean ± SEM, *p < 0.05, **p < 0.01, ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "Cre: 2777477
Emx1: 13796
Ptprd: 19266"
  },
  {
    "caption": "(D) Increased WAKE duration and decreased NREM duration during the first three hours of the light-on period and decreased REM duration in the first half of the light-on period in Ptprd-meA-/- mice (2.5-4 months). Note also that Ptprd-meA-/- mice also display increased WAKE duration and decreased NREM duration during the light-off period. (n = 8 [Ptprd-meA+/+] and 8 [Ptprd-meA-/-], mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "Decreased delta power (normalized to total power) in NREM (both light-off and light-on periods) and WAKE (light-on period) oscillations, and decreased theta power in REM (mainly light-on period) oscillations in Ptprd-meA-/- mice (2.5-4 months). (n = 8 [Ptprd-meA+/+] and 8 [Ptprd-meA-/-], mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant, two-way RM ANOVA with Holm-Sidak test).",
    "ncbi_link": "meA: 17255
Ptprd: 19266"
  },
  {
    "caption": "(C) Ex vivo lipolysis  assays on Atg7-deficient adipose tissue  explants simulated with isoproterenol  (10µM) for 1-2h (n = 5-6/group). Data are represented as mean ± s.e.m. (C, Two-Way ANOVA.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(A) Quantification of Il10  transcript levels in RAW264.7  upon stimulation to epoxy fatty acids (n = 3/group). (B) Quantification of  IL-10 protein levels in the supernatant of RAW264.7 upon stimulation to epoxy fatty acids (n = 3/group). Data are represented as mean ± s.e.m. (A,B) One-Way ANOVA.",
    "ncbi_link": "Il10: 3586"
  },
  {
    "caption": "(h) The cellular levels of Ca2+ ions after ligand (C10ORF99) stimulation of  GPR15 in human, mouse, Japanese  quail, painted  turtle. YM.254890 inhibits  Ca2+  ion levels in cells transfected with GPR15 receptors of vertebrates. The fold-change in  calcium levels was calculated based on the fluorescence intensity (excitation and emission wavelengths: 490 and 520 nm, respectively).",
    "ncbi_link": "GPR15: 71223
GPR15: 2838"
  },
  {
    "caption": "(i, j) The cellular levels of  Ca2+ ions after ligand (C10ORF99) stimulation of GPR15 in coelacanth, Asian bony tongue, and their mutants. (k, l) The cellular levels of Ca2+ ions after ligand (C10ORF99) stimulating  GPR15 in Japanese quail and its mutants. The fold-change in  calcium  levels was calculated based on the fluorescence intensity (excitation and emission wavelengths: 490 and 520 nm, respectively).",
    "ncbi_link": "GPR15: 102351034
GPR15: 107320109"
  },
  {
    "caption": "(a-h) The migration of  HEK293 cells expressing  mGPR15, qGPR15,  tGPR15, cGPR15,  aGPR15, and their mutants induced by ligand C10ORF99. Data information: All data shown are generated from at least three technical replicates. Error bars indicate SD (n=3). ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05 (t-test).",
    "ncbi_link": "aGPR15: 
cGPR15: 102351034
mGPR15: 71223
qGPR15: 107320109
tGPR15: 101950658"
  },
  {
    "caption": "(i-p) The migration  of CD4+ cells from GPR15-knockout mice, engineered to express mGPR15, qGPR15, tGPR15, cGPR15, aGPR15, and their mutants induced by ligand C10ORF99. Data information: All data shown are generated from at least three technical replicates. Error bars indicate SD (n=3). ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05 (t-test). Ad-NC represents  adeno-virus-based gene-delivery vector as negative control.",
    "ncbi_link": "aGPR15: 
cGPR15: 102351034
GPR15: 71223
mGPR15: 71223
qGPR15: 107320109
tGPR15: 101950658"
  },
  {
    "caption": "(a)  CCR9 expression in the small intestine  (SI) and colon  of Gallus gallus and Lonchura striata. (b) CCR9 expression in the small intestine (SI) and colon of  Chrysemys picta bellii  and Pelodiscus sinensis. (c)  CCR9 expression in the  small intestine  (SI) and colon  of Rana catesbiana Shaw and Rana nigromaculata. (d) GPR15 expression in the small intestine (SI) and colon of Gallus gallus and Lonchura striata. (e) GPR15 expression in the  small intestine  (SI) and colon of Chrysemys picta bellii  and Pelodiscus sinensis. (f)  C10ORF99 expression  in the small intestine (SI) and  colon of Gallus gallus and Lonchura striata. (g)  C10ORF99 expression in the small intestine (SI) and colon of Chrysemys picta bellii  and Pelodiscus sinensis. (h) GPR15 and C10ORF99 expression in the small intestine (SI) and colon of Rana catesbeiana Shaw and Rana nigromaculata. Data information: All data shown are representative of at least three independent technical replicates. Error bars indicate SD (n=3). UD, undetermined, ***P-value < 0.001; **P-value < 0.01; NS: no significance (t-test).",
    "ncbi_link": "C10ORF99: 
CCR9: 
GPR15: 
CCR9: 428454
GPR15: 427956"
  },
  {
    "caption": "(i) GPR15 expression in CD4+ T cell from  chicken small intestine  (SI) and  colon. Data information: All data shown are representative of at least three independent technical replicates. Error bars indicate SD (n=3). UD, undetermined, ***P-value < 0.001; **P-value < 0.01; NS: no significance (t-test).",
    "ncbi_link": "GPR15: 427956"
  },
  {
    "caption": "The expression levels of GPR15,  C10ORF99,  FOXP3 in mice fed with corn, chicken, and mixture of corn plus chicken, commercial food  chow and a positive control (propionate  added to  commercial food  chow) at different times (weanling  mice were defined as w-1) in colonic  tissue were determined by q-RT-PCR. Each symbol or bar represents pooled RNA from colon tissues from three  mice. Data information: All data shown are representative of at least three independent biological replicates.Error bars indicate SD (n=3). ****P-value < 0.0001 ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05; NS: no significance (One-way ANOVA).",
    "ncbi_link": "C10ORF99: 70045
FOXP3: 20371
GPR15: 71223"
  },
  {
    "caption": "The expression levels of IL-10  in mice fed with corn, chicken, and mixture of corn plus  chicken,  commercial food chow and a positive control (propionate added to  commercial food chow) at different times  (weanling mice were defined as w-1) in  colonic tissue were determined by  q-RT-PCR. Each symbol or bar represents pooled RNA from colon tissues from three  mice. Data information: All data shown are representative of at least three independent biological replicates.Error bars indicate SD (n=3). ****P-value < 0.0001 ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05; NS: no significance (One-way ANOVA).",
    "ncbi_link": "IL-10: 16153"
  },
  {
    "caption": "(i) Luciferase activities of constructs with the mouse C10ORF99   promoter in HEK293  cells. Data information: All data shown are representative of at least three independent biological replicates.Error bars indicate SD (n=3). ****P-value < 0.0001 ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05; NS: no significance (One-way ANOVA).",
    "ncbi_link": "C10ORF99: 70045"
  },
  {
    "caption": "Luciferase activities of constructs with the Japanese quail C10ORF99 promoter in  HEK293 cells. Data information: All data shown are representative of at least three independent biological replicates.Error bars indicate SD (n=3). ****P-value < 0.0001 ***P-value < 0.001; **P-value < 0.01; *P-value < 0.05; NS: no significance (One-way ANOVA).",
    "ncbi_link": "C10ORF99: "
  },
  {
    "caption": "B Forest plots display the hazard ratios of genes at the 17q12 amplicon according to the DFS (top right) and OS (bottom right) of breast cancer patients in the METABRIC dataset. Genes located at the HER2 amplicon were nominated according to hazard-ratio levels (all P-values < 0.01). The HER2 co-amplification percentage of the indicated genes is represented as bar graphs (left).",
    "ncbi_link": "HER2: 2064"
  },
  {
    "caption": "C The frequency of CDK12 amplification in HER2-amplified- and HER2-nonamplified breast cancer. The bar graphs indicate the frequency of HER2 and CDK12 co-amplified cases among the patients with HER2 gene amplification (left). Tables show the percentage of CDK12 amplification in the indicated cohorts (right). Amp, amplification; non-amp, non-amplification.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "D Scatter plot showing the correlation between CDK12 expression and its copy number alteration (CNA) in METABRIC (left). The r value was calculated as the Pearson's correlation coefficient. Box plots showing the mRNA levels of CDK12 in the indicated subtypes from METABRIC (right). P-values were calculated using one-way ANOVA, followed by post-hoc LSD test.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "E Survival analysis of breast cancer patients according to the expression of CDK12 in METABRIC (top) and KM plotter (bottom) using the Kaplan-Meier method with the log-rank test.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "A FACS analysis of the percentages of CD44+/CD24−/ESA+ breast CSC-like populations in CDK12-overexpressing ZR-75-30 and HCC-1419 cells and CDK12-siRNA-transfected BT474 and HCC-1954 cells. Top, representative dot plot of CD44-APC versus CD24-PE expression for viable cells (red) and ESA-positive cells (blue) from the viable cells. Bottom, the percentage of CD44+/CD24-/ESA+ cell population (blue dots at lower right quadrant in the plots) was quantified in the indicated cell lines. Mean ± s.d. of three independent samples. P-values were based on two-tailed Student's t-test (ZR-75-30 and HCC-1419 cells) and one-way ANOVA with a post-hoc LSD test (BT474 and HCC-1954 cells). Amp, amplification; non-amp, non-amplification; Trz, trastuzumab.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "B ALDEFLUOR assay for analysing cell population with a high ALDH activity in the indicated cell lines. Cells either treated with ALDH inhibitor DEAB (with DEAB; negative control) or untreated (without DEAB) were incubated with ALDEFLURO substrate (BAAA). In the FACS analysis, the percentage of ALDEFLUOR-positive population was determined based on the shift of fluorescent cells seen in the dot plots in the absence of DEAB. Mean ± s.d. . P-values were calculated based on a two-tailed Student's t-test cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "C The self-renewal of CSCs in the indicated stable cell lines was analysed using a tumorsphere-formation assay. The number of tumorsphere cells (> 100 μm in diameter) was counted after 3, 5, and 7 days. Data represent the mean ± s.d. (n = 3). P-value was calculated based on a two-tailed Student's t-test (ZR-75-30 and HCC-1419 cells) or ANOVA with a post-hoc LSD test (BT474 and HCC-1954 cells). cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "D Cell growth of the indicated stable cell lines treated with trastuzumab (Trz) or vehicle (veh) as measured by SRB assay. Trastuzumab-sensitive HER2+ breast cancer cell lines (S) and trastuzumab-insensitive HER2+ breast cancer cell lines (partial responsive, PR; resistant, R) were treated with 1 µg/mL or 100 µg/mL trastuzumab, respectively. Data represent the mean ± s.d. P-values were calculated using RM ANOVA with a post-hoc LSD test. cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "E Analysis of the effect of CDK12 deficiency on the in vivo trastuzumab response of HER2+ breast cancer. Mice were orthotopically xenografted with the indicated HER2+ breast cancer cells and treated with 20 mg/kg trastuzumab. The growth curve of each group was analysed twice weekly for 5 to 6 weeks (n = 8/group; mean ± s.e.m.). P-values were calculated using one-way ANOVA with a post-hoc LSD test for the last day of tumor measurement. cell line information was indicated as follows: a/a, CDK12-amplified/HER2-amplified cells R, trastuzumab-resistant S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "A Heatmap presents the alteration of gene expression (≥1.5-fold) between control (CON) and CDK12-overexpressing (CDK12) ZR-75-30 cells obtained from RNA-seq analysis.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "B GSEA displaying correlations of the gene-expression profiles between control and CDK12-overexpressing cells based on RNA-seq results.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "D The CDK12-target genes identified by RNA-seq were validated in CDK12-overexpressing ZR-75-30 cells using qRT-PCR analysis. Mean ± s.d. (n = 3). P-values by two-tailed Student's t-test.",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "E ChIP-qPCR analysis displaying the fold-enrichment of the indicated proteins and histone H3 acetylation at the TSS of CDK12-target genes in the indicated cell lines. Mean ± s.d. (n = 3). P-values by two-tailed Student's t-test. Cell line information: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "F Effect of CDK12 kinase inhibition on the expression of WNT1, WNT3, and IRS1. Cells were treated with different doses of dinaciclib for 12 h, and the expression of candidate targets of CDK12 were analysed by immunoblot and qRT-PCR Mean ± s.d. (n = 3). P-values by ANOVA with a post-hoc LSD test. Cell line information: a/a, CDK12-amplified/HER2-amplified cells ; R, trastuzumab-resistant; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064
IRS1: 3667
WNT1: 7471
WNT3: 7473"
  },
  {
    "caption": "G Cell viability was measured by SRB assay in trastuzumab-sensitive BT474 cells and trastuzumab-resistant HCC-1954 cells treated with 1 µg/mL or 100 µg/mL trastuzumab (Trz) and/or 5 nM or 10 nM dinaciclib (Dina), respectively. Mean ± s.d. (n = 3). P-values, RM ANOVA with a post-hoc LSD test. Cell line information: a/a, CDK12-amplified/HER2-amplified cells R, trastuzumab-resistant; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "H Tumor growth curves for mice xenografted with the indicated HER2+ breast cancer cells treated with 20 mg/kg trastuzumab and/or 20 mg/kg dinaciclib (n = 8/group; mean ± s.e.m.). P-values, one-way ANOVA with a post-hoc LSD (BT474) or Dunnett T3 (HCC-1954) test for the last day of tumor measurement. Cell line information: a/a, CDK12-amplified/HER2-amplified cells R, trastuzumab-resistant; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "A Western blot and qRT-PCR results showing phosphorylation levels of GSK-3β and WNT1 and WNT3 expression, respectively, in the indicated cell lines. Mean ± s.d. (n = 3). P-values by two-tailed Student's t-test. a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; S, trastuzumab-sensitive",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "Subcellular localization of β-catenin in the indicated stable cell lines were analysed by immunofluorescence staining (C). Nuclear translocation of β-catenin in control, CDK12-overexpressing, and CDK12-knockdown stable cell lines was quantified by counting the cells harboring exclusively nuclear β-catenin (N) from the immunofluorescence image. Mean ± s.d. (n = 3). P-value was calculated using a two-tailed Student's t-test. M+C, cells containing membrane and/or cytoplasmic β-catenin; N, cells dominantly expressing nuclear β-catenin. Green, β-catenin staining; Blue, DAPI staining for visualization of nucleus; Scale bar = 10 μ. a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "D Luciferase-reporter assay measuring the TCF/ lymphoid enhancer-binding factor-promoter activity in the indicated cell lines. TOP, pTOP-flash (wild-type TCF-binding sites), FOP, pFOP-flash (mutant TCF-binding sites). Data represent the mean ± s.d. P-values were calculated using a two-tailed Student's t-test.",
    "ncbi_link": "TCF: 3172
lymphoid enhancer-binding factor: 51176"
  },
  {
    "caption": "E The mRNA levels of the WNT/β-catenin/TCF-target genes in CDK12-overexpressing ZR-75-30 cells and CDK12-knockdown BT474 cells were analysed by qRT-PCR. Mean ± s.d. (n = 3). P-values were calculated using a two-tailed Student's t-test.",
    "ncbi_link": "CDK12: 51755
β-catenin: 1499
TCF: 3172
WNT: 54361///7476///7472///80326///7482///7475///7484///7474///7471///89780///7478///7479///7473///7480///7481///51384///81029///7483///7477"
  },
  {
    "caption": "F Effect of WNT/ β-catenin/TCF pathway on the CDK12 regulation of breast CSCs. Cells were treated with DMSO (vehicle) or 10 nM FH535, a β-catenin/TCF inhibitor, for 24 h, and changes in the CD44+/CD24-/ESA+ cell population were measured using FACS analysis. Cells seen at lower right quadrant in the dot plots indicate CD44+/CD24- population (red) and CD44+/CD24-/ESA+ population (blue). Data represent the mean ± s.d. ofP-value was calculated using one-way ANOVA with a post-hoc LSD test.",
    "ncbi_link": "CDK12: 51755
β-catenin: 1499
TCF: 3172
WNT: 89780///7481///80326///7483///7471///7480///7472///81029///7474///7473///7476///7484///7479///54361///7475///7478///51384///7477///7482"
  },
  {
    "caption": "A Human phospho-RTK array displaying the activation of phosphokinase-related proteins in CDK12-knockdown BT474 cells. The bar graph shows the fold change of spot intensity. Cell line information: a/a, CDK12-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "B Immunoblots showing the levels of the indicated proteins in different types of HER2+ breast cancer stably expressing CDK12 or with CDK12 knocked down. Cell line information: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant; PR, trastuzumab-partial responsive; S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "Co-IP analysis showing the amounts of bindings between ErbB receptors. Cell lysates from CDK12-overexpressing ZR-75-30 cells were immunoprecipitated with anti-HER2 antibody and immunoblotted using the indicated antibodies. IgG, negative control. Cell line information: ; n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "D Western blot and qRT-PCR analysis of the phosphorylation levels and expression of IRS1, respectively, in the indicated cell lines. Mean ± s.d. (n = 3). P-values were calculated using a two-tailed Student's t-test. Cell line information: a/a, CDK12-amplified/HER2-amplified cells; n/a, CDK12 non-amplified/HER2-amplified cells; R, trastuzumab-resistant S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "E Co-IP analysis indicating the amounts of IRS1 protein interaction with ErbB receptors and p85 in CDK12-overexpressing ZR-75-30 cells. Cell line information n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064"
  },
  {
    "caption": "F IRS1 effect on CDK12-induced phosphorylation of ErbB receptors. Lysates from cells treated with either control siRNA or IRS1 siRNA (siIRS1) for 24 h were subjected to immunoblotting with the indicated antibodies. Cell line information: n/a, CDK12 non-amplified/HER2-amplified cells S, trastuzumab-sensitive.",
    "ncbi_link": "CDK12: 51755
HER2: 2064
IRS1: 3667"
  },
  {
    "caption": "(A) UCSC genome browser view of normalized TT-seq  coverage on the plus and minus strand at the TAL1 locus (hg38; chr1:47,194,268-47,242,880; (Kent et al., 2002)) in the leukemia cell lines Jurkat  and K562. For better visualization, TT-seq  coverage is cut at 200 (purple lines). eRNAs are shown between the  plus and minus strand. Red line indicates the short 12 bp insertion in Jurkat  cells, introducing novel binding sites for the transcription factor  MYB",
    "ncbi_link": "TAL1: 6886"
  },
  {
    "caption": "(B) UCSC genome browser view of normalized  TT-seq  coverage on the  plus and minus strand at the 2.8 Mbp gene desert surrounding MYC (hg38; chr8:127,042,406-129,779,109; (Kent et al., 2002)) in fourteen cancer  cell lines. eRNAs represent the union from all cell lines. Genome-wide association studies (GWAS) risk loci contain GWAS  single nucleotide polymorphisms  (SNPs) for prostate cancer (PrCa), acute lymphocytic leukemia (ALL), breast cancer (BrCa),  colorectal cancer (CRC), and glioblastoma (GBM) including SNPs in linkage disequilibrium (r2 ≥ 0.8). TT-seq coverage is displayed between 8-250 to allow for better visualization of the eRNA signal surrounding MYC. Dashed rectangle is shown at full scale on the right. Note: TT-seq reads were mapped against the hg38 reference genome and we cannot rule out the existence of genomic rearrangements (e.g. translocations) affecting the shown region in the used cancer cell line clones.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(E) UCSC genome browser view of normalized TT-seq coverage on the plus and minus  strand at the  PHLDA1  locus (hg38; chr12:75,612,350-76,042,552; in the  colorectal cancer cell line HCT 116. TT-seq coverage is cut at 250 (purple lines) to allow for better visualization.  eRNAs are shown between the plus and minus strand. Aggregated  transcription factor ChIP-seq peak regions (TF ChIP-seq) comprise ChIP-seq binding profiles of 19 TFs in HCT 116  cells from CISTROME The height of the signal indicates the number of different TFs binding at a particular region. Binding  regions for selected TFs (TCF7l2, YY1, SP1) are shown below together with p300 and RNA polymerase II (Pol II). TT-seq enhancer regions are shown at the bottom together with a  H3K27ac-defined super-enhancer  annotation, which was downloaded from SEdb 2019). At date of publication no Med1 ChIP-seq data was available for HCT 116.",
    "ncbi_link": "PHLDA1: 22822"
  },
  {
    "caption": "UCSC genome browser view of normalized TT-seq coverage on the plus and minus strand at the BMP4 locus (hg38; chr14:53,935,697-54,264,430; in LoVo colorectal cancer cells. TT-seq  coverage is cut at 500 (purple lines) to allow for better visualization.  eRNAs and enhancers are shown above and below the  minus  strand, respectively. Aggregated transcription factor ChIP-seq  peak regions (TF  ChIP-seq) include ChIP-seq binding profiles of 326 TFs in LoVo  cells The height of the signal indicates the number of different TFs  binding  at a particular region. Significant promoter capture  Hi-C (CHi-C)  interactions are shown in purple",
    "ncbi_link": "BMP4: 652"
  },
  {
    "caption": "B. Exponentially growing S. cerevisiae WT, ste∆ and tag∆ cells were treated with 100 µg/mL zeocin and samples collected at the indicated timepoints for western blot analysis and cytometry The activation of the DDR was monitored following the progressive phosphorylation of its downstream effector kinase Rad53. The unphosphorylated and phosphorylated isoforms of Rad53 are indicated (Rad53 and Rad53-P, respectively). Ponceau staining is shown as a loading control. The percentage of Rad53-P was quantified at each point by dividing the raw signal of the upper band by the total signal in that lane, thus plotted in the graph shown on the right. The plotted values represent the mean value of at least 3 independent experiments and the variation is represented by the SEM. Unpaired t-tests were used to compare the potential differences of the means at each time point. Only the p-value(s) for those being significantly different are indicated. C. Identical to (B) but comparing unloaded WT and WT pre-loaded for 2 h with 0.05% oleate in order to inhibit sterol esterification.",
    "ncbi_link": "ste: 855753///850415
tag: 855742///854419"
  },
  {
    "caption": "A. Exponentially growing S. cerevisiae WT and yeh2∆ cells were treated with 100 µg/mL zeocin and samples retrieved at the indicated timepoints for Western blot analysis and cytometry The activation of the DDR was monitored following the progressive phosphorylation of its downstream effector kinase Rad53. The unphosphorylated and phosphorylated isoforms of Rad53 are indicated (Rad53 and Rad53-P, respectively). Ponceau staining is shown as a loading control. The percentage of Rad53-P was quantified at each timepoint and plotted in the graph shown on the right. The plotted values represent the mean value of at least 3 independent experiments and the variation is represented as the SEM. Unpaired t-tests were used to compare the potential differences of the means at each time point. Only the p-value(s) for those being significantly different are indicated.",
    "ncbi_link": "yeh2: 850707"
  },
  {
    "caption": "C. Exponentially growing S. cerevisiae WT and ste∆ cells were treated with 100 µg/mL zeocin and samples retrieved at the indicated timepoints for inspection by fluorescence microscopy. The establishment of DNA resection factories was assessed by counting the number of Rfa1-CFP foci per cell. Scale bar is 4 µm. Left: the mean values of each timepoint of three independent experiments were used to obtain this graph (mean and SEM). Unpaired t-tests were used to compare the potential differences of the means at each time point. Only the p-value(s) for those being significantly different are indicated. Right: representative images of both strains at timepoint 120 min. Scale bar is 4 µm.",
    "ncbi_link": "ste: 855753///850415"
  },
  {
    "caption": "D. WT and yeh2∆ cells carrying a plasmid bearing the HO nuclease gene under a galactose-inducible promoter were exposed to 2% galactose to trigger the expression of the HO nuclease to cut at the MAT locus, and samples were retrieved at the indicated time points for genomic DNA extraction. Subsequent SspI  digestion, in combination with the use of a probe targeted to MAT, allows defining the fate of the cut fragment by Southern blot analysis. As resection progresses on DNA, SspI  restriction sites are lost, leading to progressively longer ssDNA fragments (whose sizes are indicated at the right of the gel) that can be separated on an agarose gel under denaturing conditions. Given the much stronger signal of the \"cut\" fragments with respect to the \"resected\" fragments, the gel has been split into low and high contrast halves, respectively. The ssDNA over cut yet unresected DSB molecules was calculated for each shown resection intermediate. The graph on the right plots the sum of all these values (cumulative ssDNA/DSB) for a given resected intermediate during the interval from 90 to 240 min. The error bar is the SEM of three independent experiments. * derives from applying a t-test that compares the two populations of values.",
    "ncbi_link": "SspI: 
HO: 851371
yeh2: 850707"
  },
  {
    "caption": "B. Recombination assay details as in (A) using WT, rad3-102, ste∆ and rad3-102 ste∆ strains.",
    "ncbi_link": "ste: 855753///850415
rad3: 856918"
  },
  {
    "caption": "A. Exponentially growing S. cerevisiae WT, ste∆, tag∆ and yeh2∆ cells were treated with 100 µg/mL zeocin for 90 minutes. This treatment duration recurrently results in more cells accumulating in the G1 phase of the cell cycle After 90 min, cells were washed to remove zeocin and resuspended in fresh, zeocin-free medium, and samples were retrieved every hour, as indicated. All samples were processed for western blot analysis and cytometry. The de-activation of the DDR was monitored following the progressive de-phosphorylation of Rad53. The unphosphorylated and phosphorylated isoforms of Rad53 are indicated (Rad53 and Rad53-P, respectively). Ponceau staining is shown as a loading control. Top: samples were migrated using commercial 3-8% gradient gels. Bottom: samples were migrated in home-made resolutive gels (see M&M).",
    "ncbi_link": "ste: 855753///850415
tag: 855742///854419
yeh2: 850707"
  },
  {
    "caption": "D. Proximity ligation assay (PLA) to assess whether ATM and PI(4)P are in close proximity (< 40 nm). Top: representative pictures of RPE-1 cells, in which PLA signals are pictured in green. Size bar is 10 µm. Bottom left: the graph shows the mean PLA signal area occupied per cell when doing the experiment with both antibodies (experiment) or by omitting one primary antibody at a time (technical controls). In practice, each point is the value of having measured all the PLA signals present in one photo (20 to 40 cells) and divided this value by the number of nuclei. To account for reproducibility, we used SuperPlots to draw the graphs each independent experiment is plotted in a different colour, where the mean value of each independent experiment is highlighted by a more intense colour than the individual values of that experiment, for which the colour is more translucid. Last, the solid horizontal line marks the mean of the means. A one-way ANOVA for multiple comparisons was applied to evaluate whether there were significant differences between the means. Bottom right: the graph shows the mean PLA signal area occupied per cell when doing the experiment either in cells transfected with an siRNA Control (experiment) or with three different siRNAs targeted against ATM (biological controls). The meaning of each plotted point, of the horizontal line and the statistical analysis is as explained above.",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": "D. Exponentially growing S. cerevisiae WT cells transformed with an empty vector ("control") or with a plasmid overexpressing OSH4 were treated with 100 µg/mL zeocin and samples collected at the indicated timepoints for inspection by fluorescence microscopy to evaluate the percentage of cells displaying GFP-Tel1 foci. Top: illustrative images of GFP channel (nuclear Tel1 signals) in the indicated conditions. Note that we systematically monitor mCherry-Pus1 to ascertain whether signals are nuclear or not. Scale bar is 6 µm. Bottom: graph displaying the mean value of the percentage of cells forming GFP-Tel1 foci and the SEM of 3 independent experiments for the indicated conditions. Unpaired t-tests were used to compare the potential differences of the means at each time point. Only the p-value(s) for those being significantly different are indicated.",
    "ncbi_link": "OSH4: 28934456"
  },
  {
    "caption": "B. Top: RPE-1 cells transfected after 3 days with siRNA control or against OSBP1 (3 different siOSBP1 sequences were assessed independently) were exposed to 0.005% MMS for the indicated times and the phosphorylation status of KAP-1 on Ser 824 was assessed by western blot. Total KAP-1 signals and the Ponceau staining are used as loading controls. Bottom: graph displaying the P-KAP-1 / KAP-1 ratio. Each plotted value is the mean out of three independent experiments, and the error bars account for the SEM. The displayed p-value highlights the significant difference of the concerned means after applying an unpaired t-test.",
    "ncbi_link": "OSBP1: 5007"
  },
  {
    "caption": "G, Michaelis-Menten uptake kinetics  of 3H-GABA by the GAT1WT used in the study displaying a KM  value of 11.4 μM.",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "I, Inhibition  of  3H-GABA uptake  through  GAT1WT by tiagabine  (Ki= 725 nM), NO711  (1.07 μM) and SKF89976a  (7.3 μM). Data information: All measurements of  inhibition potency  were the result of two independent experiments performed in triplicate (n=6) and all the points were used for calculating the values where the error bars represent s.e.m.",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "Changes to Michaelis-Menten kinetics  for L300F mutant that displays weakened 3H-GABA uptake   activity with KM  = 20.9 μM. A near 10-fold loss of  nipecotic acid inhibition potency  was observed at a value of 134.3 μM. The inhibition potencies of the inhibitors display lowered value suggesting an improved ability to compete for the GABA uptake. Data information: All data plots were performed as two independent experiments each time done in triplicate (n=6). Error bars in the data display s.e.m. Statistical significance of inhibition potencies were measured between the mutant and GAT1WT transporter measured with an unpaired t-test display p values as follows;  nipecotic acid,",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "Changes to Michaelis-Menten kinetics  for L300F mutant that displays weakened 3H-GABA uptake  activity with KM  = 20.9 μM. The inhibition potencies of the inhibitors display lowered value suggesting an improved ability to compete for the GABA uptake. Data information: All data plots were performed as two independent experiments each time done in triplicate (n=6). Error bars in the data display s.e.m. Statistical significance of  inhibition potencies were measured between the mutant and GAT1WT transporter measured with an unpaired t-test display p values as follows panel E-0.0001; tiagabine, panel F-0.0017; NO711, panel G-0.018; SKF89976a",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "E, F, Eadie-Hofstee plots of E, tiagabine  and F, NO711  display competitive mode of inhibition of 3H GABA uptake  in GAT1WT. G, Eadie-Hofstee plot of SKF89976a  displaying mixed (competitive+non-competitive) inhibition  of 3H-GABA uptake  in  GAT1WT. Data information: (E-G) Concentrations of the inhibitors were decided based on the Ki  values calculated for individual inhibitors. Each data point was plotted using 6 measurements carried out in two independent measurements in triplicates. Error bars represent s.e.m.",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "C, Michaelis-Menten kinetics   of GAT1WT and GAT1  S359E displays a weakened KM  value (28.54 ± 2.3 μM). The enhanced Vmax  is a consequence of the enhanced expression of the mutant transporter in the assayed cells monitored by FSEC. Data information: The kinetic  plots were plotted as a mean of 6 measurements carried out in two independent measurements in triplicate. The error bars represent s.e.m.",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "D, 3H-GABA uptake inhibition  by the substrate analogue nipecotic acid for GAT1  S359E displaying a Ki  value of 30.1 μM Data information: The kinetic  plots were plotted as a mean of 6 measurements carried out in two independent measurements in triplicate. The error bars represent s.e.m.",
    "ncbi_link": "GAT1: 79212"
  },
  {
    "caption": "E, The equivalent mutation in dDATWT E384S causes a complete ablation of transport activity despite retaining similar expression levels as dDATWT. Data information: The kinetic plots were plotted as a mean of 6 measurements carried out in two independent measurements in triplicate. The error bars represent s.e.m.",
    "ncbi_link": "DAT: 36849"
  },
  {
    "caption": "A) Quantification of the effect of individual BCL-2-family proteins on HCT AKO cell death, measured as percentage of cells showing released cyt c or pyknotic nuclei. Data correspond to at least three independent experiments, n>30 cells per condition per experiment. *** p<0,001 and * p<0,05 with respect to GFP condition.",
    "ncbi_link": "BCL-2: 596"
  },
  {
    "caption": "C) Western blot analysis of SMAC and cyt c release in GFP-BAX, tBID-GFP and GFP-BCLXL expressing cells at 12 h, 16 h and 24 h after transfection in HCT AKO. SN (supernatant, cytosolic fraction), P (pellet, membrane fraction) and PS (Ponceau Staining).",
    "ncbi_link": "BCLXL: 
GFP: 
BAX: 581
tBID: 637"
  },
  {
    "caption": "F) Kinetics of the expression of tBID-GFP (blue) and PI intake upon tBID expression (purple) and unstransfected HCT116 AKO cells (in grey). Plots show the average fluorescence intensity (dark lines) and its standard deviation (shaded areas) from 3 technical replicates and 3 independent experiments. Fluorescence intensity was obtained by analysis the total fluorescence per well using incucyte system every 60 min.",
    "ncbi_link": "GFP: 
tBID: 637"
  },
  {
    "caption": "G) Quantification of PI+ cells from total transfected cells with GFP-BAX, tBID-GFP, GFP-BCLXL and GFP. n=3 independent experiments with >10000 cells per condition per experiment. *** p<0,001 with respect to untransfected condition.",
    "ncbi_link": "BCLXL: 
GFP: 
BAX: 581
tBID: 637"
  },
  {
    "caption": "H) Cell death induced by tBID-GFP in HCT AKO cells in the absence and presence of ZVAD, NSA and Ferrostatin-1. Data correspond to three independent experiments, n>30 cells per condition per experiment. *** p<0,001 with respect to MOCK condition.",
    "ncbi_link": "GFP: 
tBID: 637"
  },
  {
    "caption": "A) Representative confocal immunofluorescence and bright field (BF) images of HCT DKO cells expressing tBID-GFP (in green) treated or not with COMBO (ABT737 + S63586). Cyt c shown in magenta and nuclei in cyan. Scale bar 10 µm. B) Effect of tBID-GFP and mCherry-BCLXL on cell death, measured as percentage of cells showing released cyt c or pyknotic nuclei. Data correspond to at least three independent experiments, n> 30 cells per condition per experiment. *** p<0,001, ** p<0,025 and * p<0,05 with respect to tBID-GFP in HCT AKO condition.",
    "ncbi_link": "BCLXL: 
GFP: 
mCherry: 
tBID: 637"
  },
  {
    "caption": "J) Representative HyVolution - superresolution images of TFAM-RFP expressing U2OS BAX/BAK DKO cells in the in the absence (top) and presence of tBID-GFP (bottom). TFAM appears in red, TOM20/mitochondria in grey and tBID-GFP in green.",
    "ncbi_link": "GFP: 
BAK: 578
BAX: 581
tBID: 637"
  },
  {
    "caption": "K) Quantification of cells with TFAM release on U2OS BAX/BAK DKO cells transfected with GFP-BAX/tBID-GFP and TFAM-RFP in the presence/ absence of COMBO. Dots correspond to individual experiments (n=3 individual experiments with more than 10 cells per condition per experiment). Unpaired Student's t-test *** p<0,001 with respect to non-treated conditions.",
    "ncbi_link": "GFP: 
RFP: 
TFAM: 
BAK: 578
BAX: 581
tBID: 637"
  },
  {
    "caption": "B) Cell death induced by tBID-GFP and its variants on HCT AKO, measured as percentage of cells showing released cyt c or pyknotic nuclei. Data correspond to three independent experiments, with n> 30 cells per condition per experiment. *** p<0,001 and * p<0,05 with respect to tBID-GFP WT condition.",
    "ncbi_link": "GFP: 
tBID: 637"
  },
  {
    "caption": "D) Effect of tBID wt and α6-mutants overexpression on HCT AKO cells, measured as DRAQ7+/GFP+ cells and normalized to tBID wt condition. n=3 independent experiments, ** p<0,025 and * p<0,05 with respect to tBID-GFP wt condition. E) Effect of tBID wt and α6-mutants overexpression on MEF BID KO cells, measured as DRAQ7+/GFP+ cells and normalized to tBID wt condition. Effect of GFP overexpression on BID KO cells relative to tBID wt was assessed by pyknotic nuclei formation quantification. n=3 independent experiments *** p<0,001 with respect to tBID-GFP wt condition.",
    "ncbi_link": "GFP: 
BID: 12122
tBID: 637"
  },
  {
    "caption": "A) Representative CLEM images of mitochondria in HCT AKO cells (control) and HCT AKO cells expressing GFP-BAX or tBID-GFP. Black arrows indicate MOM disruptions. B-D) Effect of GFP -BAX and tBID-GFP on HCT AKO mitochondrial structure. (B) Number of disruptions at the MOM per mitochondrial area, each dot represents an individual cell. (C) Mean area per mitochondrion at the condition tested, each dot represents an individual mitochondrion. (D) Analysis of cristae morphology, each dot represents an individual crista. Cristae shape calculated as length/width. Data represent n>50 mitochondria from 3-5 independent cells. In B-D), boxes represent 96% confidence interval, the average is represented by the line inside the box and whiskers correspond to S.D. The statistical significance was assessed by unpaired Student's t-test. *** p<0,001 and ** p<0,025 with respect to HCT AKO or untransfected condition.",
    "ncbi_link": "GFP: 
GFP.: 
BAX: 581
tBID: 637"
  },
  {
    "caption": "D) Representative kinetics of cell death, represented as DRAQ7+ cells in Nalm6 199R cells (grey), Nalm6 199R BID KO #1 cells (blue) and Nalm6 199R BID KO #5 cells (purple) upon 250 ng/ml TRAIL treatment. Plots show the average fluorescence intensity (dark lines) and its standard deviation (shaded areas) from 5 technical replicates. Fluorescence intensity was obtained by analysis the total fluorescence per well using incucyte system every 60 min.E",
    "ncbi_link": "BID: 637"
  },
  {
    "caption": "H) Cell death induced by GFP-BAK and GFP-BAK R127H on HCT AKO, measured as DRAQ7+/GFP+ cells. Unpaired Student's t-test. *** p<0,001 with respect to GFP BAK wt.",
    "ncbi_link": "GFP: 
BAK: 578"
  },
  {
    "caption": "I) Effect of 24 h incubation with 250 ng/ml TRAIL on Nalm6 199R, Nalm6 199R BAK KO and Nalm6 199R BOK KO, measured as DRAQ7+ cells with respect of total cell surface and normalized to untreated conditions. Each dot corresponds to the average normalized value of 3-4 technical replicates in n=3 independent experiments.",
    "ncbi_link": "BAK: 578
BOK: 666"
  },
  {
    "caption": "(C,D) Localization of SGN1-Citrine and lignin deposition patterns in pCASP1::SGN1-Citrine lines in wild-type (Col) and different mutant backgrounds (sgn1, sgn3, cif1 cif2) (C). myrpalm-SGN1-Citrine localization and lignin deposition patterns in pCASP1::myrpalm-SGN1-Citrine lines (D). Lignin (Basic Fuchsin) and cell walls (Calcoflour White) are shown in magenta and white respectively. For this experiment, two or three independent lines were tested. From each transgenic line, 2 positions from 12 roots were observed and representative pictures are shown in the figure. Schematics are indicating the position of optical sections in a 3D illustration. White arrows in (D) highlight excess lignification on the pericycle-facing (inner) side. Scale bars = 5 µm. Data information: "inner" designates the stele-facing endodermal surface, "outer", the cortex-facing surface.",
    "ncbi_link": "Citrine: 
cif1: 829112
SGN1: 842455
sgn1: 842455
cif2: 829612
CASP1: 818183
sgn3: 827760"
  },
  {
    "caption": "(A) Quantification of defects in CSD formation as number of holes per 100 µm in the CASP1-GFP domain at around 10 cells after onset of CASP1-GFP expression in 5-day-old seedlings. In the box plot, boxes indicate ranges from first to third quartiles, bold central lines display median. Upper and lower whiskers extend to maximum or minimum values no further than 1.5 times IQR (interquartile range, the distance between the first and third quartiles). One-way ANOVA was performed followed by Tukey's test. Different letters show significant statistical differences. (p<0.05, One-way ANOVA and Tukey's test, 12 roots in total were observed for each condition in two independent assays).",
    "ncbi_link": "GFP: 
CASP1: 818183"
  },
  {
    "caption": "(A) Localization of Citrine-RBOHD (left) or Citrine-RBOHF (right) in endodermal (en) cells. Both proteins were expressed under the control of pCASP1, an endodermis-specific promoter. Representative pictures are shown, 2 positions from 10 roots for each transgenic line were inspected. Scale bar = 5 µm.",
    "ncbi_link": "CASP1: 818183"
  },
  {
    "caption": "(B) Lignin accumulation in WT and rbohD and rbohF single mutants and a double mutant with or without 2-hour 100 nM CIF2 peptide treatment. Arrowheads indicate excess lignification. Pictures are shown as overviews (maximum projection) or median sections. Lignin and cell walls are shown with magenta (stained with Basic Fuchsin) and gray (stained with Calcofluor White) respectively. Representative pictures are shown, 12 roots (overview) and 2 positions in 12 roots (median section) were inspected. Scale bars = 20 µm (lignin overviews), 5 µm (median sections). "inner" designates the stele-facing endodermal surface, "outer", the cortex-facing surface.",
    "ncbi_link": "rbohF: 842710
rbohD: 834842"
  },
  {
    "caption": "(D) In situ H2O2 detection at Casparian strips in WT, sgn3, sgn1, rbohF, rbohD and rbohDF with or without 24-hour treatment of 1 µM CIF2. Brackets and arrowheads indicate Casparian strips (seen as uniformly whitish cell wall areas) and H2O2 production sites (black area) respectively. Scale bar = 1000 nm.",
    "ncbi_link": "sgn1: 842455
sgn3: 827760
rbohDF: 842710
rbohF: 842710
rbohD: 834842"
  },
  {
    "caption": "(A) CASP1-GFP and lignin deposition in WT, sgn3, rbohD, rbohF and rbohDF. CASP1-GFP and lignin (fuchsin) are presented in green and magenta respectively. Pictures were obtained from more than 10 roots from each background with similar results. Scale bar = 10 µm.",
    "ncbi_link": "sgn3: 827760
rbohF: 842710
rbohD: 834842"
  },
  {
    "caption": "(B) Time lapse imaging of single- or cotreatment of 10 nM CIF2 with 25 µM cycloheximide (CHX) on CASP1-GFP in cif1 cif2. Seedlings were pretreated with or without CHX for 30 min and transferred onto each medium. Scale bar = 10 µm (See also movie EV1). (C) Quantification of (B). Relative numbers of holes in CASP1-GFP domain after single- or co-treatment with CIF2 or CHX from the pictures in (B). Bars are S.D. * indicates statistical significance from all other conditions (p<0.01) after one-way ANOVA and Tukey test. 6 roots in total for each condition were observed during two independent tests. ",
    "ncbi_link": "cif1: 829112
cif2: 829612"
  },
  {
    "caption": "(D) Fold-change of 930 genes (p<0.05 and log2(Fold change) ≥1 or ≤ -1 at least one time point in one genotype) after CIF2 treatment at indicated time points in WT, cif1,2 and sgn3. Degree of the fold changes are shown in color code as indicated.",
    "ncbi_link": "cif1: 829112
sgn3: 827760"
  },
  {
    "caption": "(E) Relative expression levels of PER15 to CLATHRIN control in each genotype with or without 2-hour CIF2 treatment. Bars are S.D. (n=3). Different characters indicate statistically significant differences (p < 0.01, ANOVA and Tukey test). (F)Fold changes of PER15 in each genotype with or without 2-hour CIF2 treatment. Bars are S.D. (n=3). Different characters indicate statistical significance differences (p < 0.01, ANOVA and Tukey test). ",
    "ncbi_link": "PER15: 816328
CLATHRIN: 828557"
  },
  {
    "caption": "(G) Relative expression levels of PER49 to CLATHRIN control in each genotype with or without 2-hour CIF2 treatment. Bars are S.D. (n=3). Different characters indicate statistically significant differences (p < 0.01, ANOVA and Tukey test). (H) Fold changes of PER49 in each genotype with or without 2-hour CIF2 treatment. Bars are S.D. (n=3). Different characters indicate statistically significant differences (p < 0.01, ANOVA and Tukey test). ",
    "ncbi_link": "CLATHRIN: 828557
PER49: 829795"
  },
  {
    "caption": "(I)Relative fold changes of PER15 in pCASP1::SGN1-Citrine and pCASP1::myrpalm-SGN1-Citrine compared to the expression level in WT. Bars are S.D. (n=3). Different characters indicate statistically significant differences (p < 0.01, ANOVA and Tukey test). (J)Relative fold changes of PER49 in pCASP1::SGN1-Citrine and pCASP1::myrpalm-SGN1-Citrine compared to the expression level in WT. Bars are S.D. (n=3). Different characters indicate statistically significant differences (p < 0.01, ANOVA and Tukey test). ",
    "ncbi_link": "Citrine: 
SGN1: 842455
PER15: 816328
PER49: 829795
CASP1: 818183"
  },
  {
    "caption": "A Constitutive expression of either MPCFERM or MPCOX can rescue the slow growth phenotype of the mpc1Δmpc2Δmpc3Δ triple deletion mutant. Growth tests were performed with cells transformed with MPC1, MPC2, or MPC3 expression plasmids or with empty vectors in indicated combinations. A serial dilution of yeast cells was spotted on agar plates with glucose‐containing synthetic minimal medium with (SD+AA) or without (SD−AA) amino acids.",
    "ncbi_link": "MPC1: 852800
mpc1: 852800
MPC2: 856567
mpc2: 856567
MPC3: 853158
mpc3: 853158"
  },
  {
    "caption": "B Plasmid‐encoded MPC proteins can be detected in isolated mitochondria when Mpc1 is co‐expressed with either Mpc2 or Mpc3. Cells were grown in selective medium containing glycerol as a carbon source. MPC subunits were constitutively expressed from plasmids in indicated combinations in the mpc1Δmpc2Δmpc3Δ background and detected by Western blot using anti‐HA or anti‐Flag antibodies. Mitochondrial enzymes aconitase (Aco1) and malate dehydrogenase (Mdh1) were used as loading controls.",
    "ncbi_link": "mpc1: 852800
mpc2: 856567
mpc3: 853158"
  },
  {
    "caption": "Mpc2C3 forms a carrier complex with Mpc1, as analyzed by BN‐PAGE. When co‐expressed with Mpc1, Mpc2C3 shows the same complex pattern as Mpc3, including the 300K complex.",
    "ncbi_link": "Mpc1: 852800
Mpc2: 856567"
  },
  {
    "caption": "CYP46A1 expression levels in tumours from the TCGA dataset using 2016 WHO classification. Data are shown as the mean ± the standard error of the mean (SEM; n = 667). ***P < 0.0001. Statistical significance was determined by one‐way ANOVA.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "CYP46A1 expression levels in different molecular subtypes from the Rembrandt GBM dataset. Shown are means and SEM (n = 245). ***P < 0.0001. Statistical significance was determined by one‐way ANOVA.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "Kaplan-Meier analysis for patient OS and PFS based on high vs low expression of CYP46A1 in LGG and GBM. Data were obtained from the CGGA dataset. P-values were obtained from the log-rank test.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "qRT-PCR analysis of CYP46A1 mRNA levels in LN229 and GBM#P3 cells transfected with lentivirus expressing CYP46A1 (lenti-CYP46A1) or control sequence (lenti-Ctrl). GAPDH was used as an internal control. Shown are means and SEM (n = 3). LN229: ***P < 0.0001; GBM#P3: ***P < 0.0001. Statistical significance was determined by two-sided Student's t‐test.",
    "ncbi_link": "GAPDH: 
CYP46A1: 10858"
  },
  {
    "caption": "Western blot analysis to confirm CYP46A1 overexpression in GBM cells.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "Growth curves for GBM cells in vitro infected with lenti-Ctrl or lenti-CYP46A1 derived from trypan blue staining. Shown are means and SEM (n = 3). LN229: **P = 0.003; GBM#P3: **P = 0.002. Statistical significance was determined by two-sided Student's t‐test.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "Colony forming assay for GBM cells infected with lenti-Ctrl or lenti-CYP46A1. Shown are means and SEM (n = 3). LN229: *P = 0.013; GBM#P3: *P = 0.012. Statistical significance was determined by two-sided Student's t‐test.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "Representative H&E staining of orthotopic tumours derived from GBM cells infected with lenti-Ctrl or lenti-CYP46A1. Scale bar = 2 mm.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "Kaplan-Meier survival curve of tumour bearing mice injected with GBM cells infected with lenti-Ctrl or lenti-CYP46A1 (n = 5 per group). A log-rank test was used to assess statistical significance.",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "24OHC levels in spent media from LN229 (left) and GBM#P3 (right) cells transduced with lenti-Ctrl or lenti-CYP46A1 measured using targeted LC-MS/MS",
    "ncbi_link": "CYP46A1: 10858"
  },
  {
    "caption": "qRT-PCR analysis of 24OHC-regulated genes in GBM#P3 cells after treatment with 20 μM 24OHC for 72 h. GAPDH was used as an internal control. Data are shown as the mean ± SEM (n = 3).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Growth curves for LN229 cells transfected with control vector or SREBP1 plasmid and treated with 24OHC (0 - 40 μM) as assessed by a trypan blue test. Data are shown as the mean ± SEM (n = 3).",
    "ncbi_link": "SREBP1: 6720"
  },
  {
    "caption": "(E) HeLa cells expressing HA-Parkin with various pathogenic mutations were treated with CCCP, followed by immunocytochemistry. (A, D, and E) Higher magnification views of the boxed areas are shown in the insets. (F) Parkin colocalization with mitochondria was analyzed in >100 cells per mutation. Example figures indicative of robust colocalization (counted as 1), weak colocalization (counted as 0.5), and no colocalization (counted as 0) are shown. Error bars represent the mean ± SD values of at least three experiments.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(A) HeLa cells expressing wild-type Parkin or E3-inactivating mutations were treated with CCCP and then immunostained with the indicated antibodies. When E3-inactivating mutations were introduced into Parkin, the mitochondrial ubiquitylation signal disappeared.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(G) GFP-Parkin-expressing HeLa cells with various pathogenic mutations (Fig. 1 C) were treated with CCCP and subjected to immunoblotting. Asterisks show ubiquitylation of GFP-Parkin. Vertical black lines indicate that intervening lanes have been spliced out. IB, immunoblot; IP, immunoprecipitation.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(E) Endogenous PINK1 gradually accumulated after CCCP treatment. The first through the fifth lanes show endogenous PINK1, and the sixth lane shows overexpressed untagged PINK1. Note that the asterisk indicates a cross-reacting band because it was not affected by overproduction of untagged PINK1.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(A) PINK1 knockout (PINK1−/−) or control (PINK1+/+) MEFs were transfected with HA-Parkin, treated with CCCP, and subjected to immunocytochemistry with the indicated antibodies. Higher magnification views of the boxed areas are shown in the insets. (B) The number of MEFs with Parkin localized to the mitochondria was counted as in Fig. 3 A.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(C and D) Neither activation of Parkin nor mitochondrial degradation was observed in PINK1−/− MEFs. MEFs stably expressing GFP-Parkin were treated with CCCP for 4 h and subjected to immunoblotting (C)",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(C and D) Neither activation of Parkin nor mitochondrial degradation was observed in PINK1−/− MEFs. MEFs stably expressing GFP-Parkin were treated with CCCP for 24 h, followed by immunocytochemistry (D). IB, immunoblot; Ub, ubiquitylation.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(A) Schematic depiction of pathogenic and deletion mutants of PINK1 used in this study. MTS, mitochondria-targeting sequence; TMD, transmembrane domain. (B) Subcellular localization of Parkin in PINK1−/− cells complemented by various pathogenic and deletion mutants of PINK1-Flag. Cells were treated with CCCP. Higher magnification views of the boxed areas are shown in the insets. (C) The number of cells with Parkin-positive mitochondria was counted as in Fig. 3 A. Error bars represent the mean ± SD values of least three experiments.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(D) PINK1−/− MEFs complemented by various PINK1 mutants were treated with CCCP and subjected to immunoblotting using anti-Parkin or anti-Flag (tag of PINK1) antibodies. IB, immunoblot; Ub, ubiquitylation.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "Cell migration assays were performed using Transwell migration chambers. HCT116 cells were transfected with siRNAs targeting 11 candidate lincRNAs and cell migration activities were evaluated by Transwell migration assays (n = 3). CALIC is the lincRNA targeted by si-LINC00920.",
    "ncbi_link": "CALIC: 
LINC00920: 100505865"
  },
  {
    "caption": "Migration of colon cancer cells treated with an siRNA targeting CALIC. (n = 3)",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "Subcellular localization analysis of CALIC. RNAs were isolated from the nuclear and cytoplasmic fractions of HCT116 cells and quantified by qRT-PCR (n = 3). Nuclear controls: U6, MALAT1; Cytoplasmic control: GAPDH.",
    "ncbi_link": "CALIC: 
GAPDH: 
MALAT1: 378938
U6: 26827"
  },
  {
    "caption": "CALIC expression levels in cancer tissues. N, normal mucosa; T, tumor.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "Expression of CALIC in primary skin tumors (P) and their metastases (M). Expression of CALIC in primary skin tumors of patients without (w/o) or with (w) metastases.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "qRT-PCR analysis of CALIC expression in early (I/II) and late (III/IV) stage colon cancers. [Normal (N) n = 8, stage I/II n = 14, stage III/IV n = 26]",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "Kaplan-Meier curves for disease-free survival of colon cancer patients whose primary tumors expressed low (blue, n = 113) or high (red, n = 250) levels of CALIC.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "Biotinylated full-length CALIC or antisense CALIC (negative control) generated in vitro were incubated with lysates from DLD-1 colon cancer cells and precipitated with streptavidin beads. Precipitated proteins were resolved by SDS-PAGE followed by silver staining. The protein band indicated by the arrow was excised and subjected to mass spectrometry.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "(Top) schematic of the full-length and mutants of CALIC used for the precipitation of hnRNP-L from HCT116 cell lysates. The mutated elements are indicated by the cross marks. Se, sense transcript; AS, antisense transcript. +, detectable binding activity; -, no detectable activity. (Bottom) precipitated hnRNP-L and biotin-labeled fragments of CALIC are shown.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "RIP analysis was performed using control rabbit IgG or anti-hnRNP-L antibody. HPRT1 and the lncRNA MALAT1 were used as negative controls.",
    "ncbi_link": "HPRT1: 3251
MALAT1: 378938"
  },
  {
    "caption": "ChIRP-immunoblotting analysis of hnRNP-L association with endogeneous CALIC in HCT116 cells.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "RNA-Seq analysis of hnRNP-L- and CALIC-regulated genes in HCT116 cells. Venn diagram showing the overlap of genes differentially expressed by hnRNP-L (blue) or CALIC (purple) knockdown (B, top). Expression levels of 59 genes regulated in common in both hnRNP-L and CALIC knockdown cells relative to control siRNA experiments (B, bottom). Two biological replicates (R1 and R2) were included for each siRNA treatment. The number of genes within each category is indicated.",
    "ncbi_link": "CALIC: 
hnRNP-L: 3191"
  },
  {
    "caption": "Scatterplots showing correlations between CALIC- and hnRNP-L-regulated genes in (B). Left, co-regulated 59 genes; Right, all differentially regulated genes (DEGs). The correlation was calculated using the data except for the gene indicated by the asterisk.",
    "ncbi_link": "CALIC: 
hnRNP-L: 3191"
  },
  {
    "caption": "Genes induced by CALIC are significantly enriched in those upregulated by hnRNP-L. GSEA comparing the genes repressed by CALIC and hnRNP-L knockdown. NES, normalized enrichment score.",
    "ncbi_link": "CALIC: 
hnRNP-L: 3191"
  },
  {
    "caption": "Heatmap showing the expression levels of genes positively regulated in common by both CALIC and hnRNP-L in colon and rectal cancers. Samples are ordered based on the expression levels of AXL.",
    "ncbi_link": "CALIC: 
AXL: 558
hnRNP-L: 3191"
  },
  {
    "caption": "qRT-PCR analyses of AXL in HCT116 and LS180 cells transfected with an siRNAs targeting CALIC",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "immunoblotting (B, D) analyses of AXL in HCT116 and LS180 cells transfected with an siRNAs targeting CALIC",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "qRT-PCR analyses of AXL in HCT116 and LS180 cells transfected with an siRNAs targeting hnRNP-L.",
    "ncbi_link": "AXL: 558
hnRNP-L: 3191"
  },
  {
    "caption": "immunoblotting (B, D) analyses of AXL in HCT116 and LS180 cells transfected with an siRNAs targeting hnRNP-L.",
    "ncbi_link": "hnRNP-L: 3191"
  },
  {
    "caption": "qRT-PCR analyses of AXL in HCT116 cells infected with a lentivirus expressing wild-type CALIC (CALIC-full), CALIC-296-913 or CALIC-mut",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "HCT116 cells that had been treated with an siRNA targeting hnRNP-L or CALIC were transfected with an AXL reporter construct and subjected to luciferase assays.",
    "ncbi_link": "CALIC: 
AXL: 558
hnRNP-L: 3191"
  },
  {
    "caption": "ChIP assays were performed using anti-hnRNP-L antibody or control mouse IgG. The promoter regions of GAPDH and Egr1 were used as negative and positive controls, respectively.",
    "ncbi_link": "GAPDH: 
Egr1: 13653"
  },
  {
    "caption": "ChIP analysis of hnRNP-L association with the AXL promoter region in CALIC knockdown HCT116 cells.",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "ChIP analysis of hnRNP-L association with the AXL promoter region in HCT116 cells expressing lentiviral CALIC-full.",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "ChIRP analysis of CALIC binding to the AXL promoter. Binding of CALIC to the promoter regions of the indicated genes was compared with that of LacZ.",
    "ncbi_link": "AXL: 558"
  },
  {
    "caption": "Migratory activity of AXL knockdown HCT116 cells.",
    "ncbi_link": "AXL: 558"
  },
  {
    "caption": "Lentiviral expression of AXL restores the migration activity of HCT116 cells transfected with an siRNA targeting CALIC. Immunoblotting and qRT-PCR analyses of HA-tagged AXL and CALIC expression, respectively (left). α-Tubulin was used as a loading control.",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "Representative images of gross specimens (top) and H&E stained sections (bottom) of lung metastatic lesions in mice injected with CALIC or AXL knockdown HCT116 cells. Tumors were marked with yellow arrows. The dashed lines depict the boundary between normal and tumor tissues. (Right) Percentage of mice with lung metastases.",
    "ncbi_link": "CALIC: 
AXL: 558"
  },
  {
    "caption": "Representative images of gross specimens of primary cecal tumors (top) and liver metastatic lesions (bottom) in mice orthotopically (cecal) injected with CALIC knockdown HCT116 cells. Tumors are marked with yellow arrows. (Right) Percentage of mice with primary tumors and liver metastases.",
    "ncbi_link": "CALIC: "
  },
  {
    "caption": "A, B. A missense mutation in SPOP gene (Q165P, T >G) was identified in a PCa patient. Exome sequencing revealed that the primary tumor contained a heterozygous Q165P mutation (A) whereas the liver metastasis harbored a homozygous Q165P mutation (B).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "D, E. IHC analysis of BRD4 protein expression in SPOP wild type (WT) and mutated (MUT) PCa patient samples. The representative images of BRD4 IHC staining in both SPOP WT and MUT PCa patients are shown in (D) and the quantified IHC data are shown in (E). Scale bars: 100 µm for 20 x fields; 50 µm for 40 x fields. The red dot in (E) indicates SPOP Q165P sample. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; ** P < 0.01. See Appendix Table S4 for the detailed comparison, P values and sample number (n).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "F, G. IHC analysis of AR protein expression in SPOP WT and mutated PCa patient samples. The representative images of AR IHC staining in both SPOP WT and mutant PCa patients are shown in (F) and the quantified IHC data are shown in (G). Scale bars: 100 µm for 20 x fields; 50 µm for 40 x fields. The green dot indicates SPOP Q165P sample. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; *** P < 0.01. See Appendix Table S4 for the detailed comparison, P values and sample number (n).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "C. C4-2 cells were stably infected with the lenti-virus expressing empty vector (EV) or SPOP mutants and harvested for western blot analysis with the indicated antibodies.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "D. C4-2 xenograft tumors expressing EV or F133V and SPOP WT and Q165P PDX tumors were harvested for western blot analysis with the indicated antibodies. T1: tumor 1; T2: tumor 2.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "E. Representative IHC images of PTEN protein in SPOP WT and Q165P PDX tumors. Scale bars: 100 µm for 20 x fields; 50 µm for 40 x fields.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Co-IP assay was performed to detect the efficiency of dimerization between SPOP WT and Q165P mutant (F)",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Co-IP assay was performed to detect the interaction between CULLIN3 with SPOP WT or Q165P (G).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "A. DU145 PCa cells infected with virus expressing EV or SPOP Q165P were harvested for western blot analysis.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Clonogenic survival assay was performed to determine the sensitivity of NEO2734 in SPOP Q165P DU145 cells. The survival curve showed IC50 for SPOP Q165P (0.69 µM) and EV cells (1.08 µM) (C).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "DU145 cells expressing lenti-EV or lenti-HA-SPOP-Q165 constructs were treated with 1 µM of NEO2734 for 4 days and cultured for another 8 days before harvest. The number of colonies with more than 50 cells was counted. Representative images of colonies are shown in (D) with quantitative data shown in (E). All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, ** P < 0.01.",
    "ncbi_link": "HA: 
SPOP: 8405"
  },
  {
    "caption": "F. DU145 cells were treated with the indicated inhibitors and harvested for ChIP with BRD4 antibody. The enrichment of BRD4 at c-MYC enhancer and RAC1 promoter was analyzed using qPCR. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; n.s., not significant, * P < 0.05, ** P < 0.01.",
    "ncbi_link": "BRD4: 23476
c-MYC: 4609
RAC1: 5879"
  },
  {
    "caption": "G. DU145 cells were treated with the indicated inhibitors and harvested for ChIP with Ac-H3 antibody. The level of Ac-H3 at c-MYC enhancer and RAC1 promoter is analyzed using qPCR. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; ** P < 0.01.",
    "ncbi_link": "H3: 
c-MYC: 4609
RAC1: 5879"
  },
  {
    "caption": "Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were harvested for western blot analysis with the indicated antibodies (A) Asterisk, SRC3 at expected molecular mass.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were harvested for IFC with p-AKT-S473 antibody (B). E-cadherin antibody was used to indicate the cell membrane (red) and DAPI for nucleus (blue). Scale bars: 25 µm.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were cultured for five days, followed by the treatment with JQ1 (2 µM), CPI-637 (2 µM), JQ1 (2 µM) + CPI-637 (2 µM) or NEO2734 (2 µM) for five more days. The representative images of organoids after the treatment are shown in (C)",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "Six organoid lines including four SPOP WT (BM1, BM5, ST1 and 313HR) and two MUT (573R and ASC1) were cultured for five days, followed by the treatment with JQ1 (2 µM), CPI-637 (2 µM), JQ1 (2 µM) + CPI-637 (2 µM) or NEO2734 (2 µM) for five more days. the quantified data of the organoid diameter are shown in (D). Scale bars: 25 µm. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; n.s., not significant, * P < 0.05, ** P < 0.01, *** P < 0.001.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "E, F. 313HR (SPOP WT) and 573R (Q165P) organoids were cultured for 5 days, followed by the treatment with the indicated inhibitors for 5 days. The organoids were stained with Caspase-3 antibody (green) to detect apoptotic cells. E-cadherin antibody staining was used to define the cell membrane (red) and the nucleus was counterstained with DAPI (blue). The representative images of cleaved Caspase-3 IFC staining are shown in (E). Scale bars: 25 µm. All data shown are means ± SEM. The P value was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, *** P < 0.001.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "A. C4-2 PCa cells infected with virus expressing EV, SPOP Q165P or F133V were harvested for western blot analysis.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "C. Clonogenic survival assay was performed to determine the sensitivity of NEO2734 in SPOP mutant C4-2 cells. The survival curve showed IC50 for EV (1.01 µM), SPOP Q165P (0.621 µM) and SPOP F133V cells (0.395 µM).",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "F - H. A schematic depicts the procedure of the establishment of SPOP mutant xenograft models and inhibitor administration (F). When the tumor reached 100 mm3, mice were treated with vehicle (40% polyethylene glycol), JQ1 (50 mg/kg) or NEO2734 (30 mg/kg) five days a week for three consecutive weeks. Tumors isolated from mice at day 21 of treatment were photographed (G) and tumor growth are shown in (H). All data shown are means ± SEM. The P value comparing the tumor volume at day 21 post- treatment was calculated by the unpaired two-tailed Student's t-test; * P < 0.05, ** P < 0.01; *** P < 0.001.",
    "ncbi_link": "SPOP: 8405"
  },
  {
    "caption": "HEK293A cells were transfected with expression plasmids for Siglec‐7, Siglec‐5 or Siglec‐14, and then subsequently incubated with (red) or without (gray) recombinant Hsp70 (bottom panels). Flow cytometry analysis reveals Hsp70 binding to cell surfaces of HEK293A cells expressing Siglec‐5 and Siglec‐14, but not Siglec‐7. Histogram of Siglec expression after transfection is shown as blue lines (top panels).",
    "ncbi_link": "Siglec‐14: 100049587
Siglec‐5: 8778
Siglec‐7: 27036"
  },
  {
    "caption": "Using flow cytometry, undifferentiated or PMA‐differentiated THP1 cells with empty vector (EV), Siglec‐5 (Sig5), or Siglec‐14 (Sig14) overexpression were assessed for the presence of endogenously secreted Hsp70 bound on the cell surface. The mean fluorescence intensity (MFI) of signals from an anti‐Hsp70 antibody on unpermeabilized THP1 cells is shown.",
    "ncbi_link": "Siglec‐14: 100049587
Siglec‐5: 8778"
  },
  {
    "caption": "Secretion of pro‐inflammatory cytokine TNFα by THP1 cells transfected with an empty vector (EV) or Siglec‐5 (Sig5) expression plasmid was evaluated by ELISA after concurrent exposure with LPS and 10 μg/ml Hsp70 or LPS alone. Secretion of TNFα was reduced only in THP1 Sig5 cells exposed to both LPS and Hsp70 but not LPS alone.",
    "ncbi_link": "Sig5: 8778
Siglec‐5: 8778"
  },
  {
    "caption": "Similarly, IL‐8 secretion from THP1 EV and Sig5 cells was evaluated by ELISA after concurrent exposure with LPS and 10 μg/ml Hsp70. Secretion of IL‐8 was also reduced in only THP1 Sig5cells exposed to both LPS and Hsp70 but not LPS alone.",
    "ncbi_link": "Sig5: 8778"
  },
  {
    "caption": "THP1 Sig5 cells were incubated with Hsp70, and the levels of SHP‐1 recruitment to Siglec‐5 were evaluated by immunoprecipitation of Siglec‐5 and Western blot for SHP‐1. Higher levels of SHP‐1 were co‐immunoprecipitated with Siglec‐5 when the cells were incubated with Hsp70.",
    "ncbi_link": "Sig5: 8778"
  },
  {
    "caption": "Western blots demonstrate phosphorylated p38 (p‐p38) was reduced in THP1Siglec‐5cells when exposed to both LPS and Hsp70 in comparison with LPS alone. This reduction was also greater in THP1Siglec‐5cells in comparison with the control THP1cells. Numbers below immunoblots indicate densitometric analysis of each band normalized to the respective cell line's unstimulated control group, divided by the respective loading control (total p38).",
    "ncbi_link": "Siglec‐5: 8778"
  },
  {
    "caption": "Secretion of pro‐inflammatory cytokine IL‐8 by PMA‐differentiated THP1 EV or THP Sig5 cells was evaluated by ELISA after concurrent exposure with 10 ng/ml LPS with an anti‐Hsp70 antibody or isotype‐matched antibody. Secretion of IL‐8 was increased in only THP1 Sig5 cells exposed to LPS and an anti‐Hsp70 antibody in comparison with the isotype control antibody, but this increase was not replicated in THP1 EV cells.",
    "ncbi_link": "Sig5: 8778"
  },
  {
    "caption": "Secretion of TNFα by THP1 cells transfected with a Siglec‐5 or Siglec‐14 expression vector was evaluated by ELISA after exposure to Hsp70 at the various concentrations in the presence of endotoxin‐neutralizing agent polymyxin B. Only THP1 Siglec‐14 cells exhibited significant secretion of TNFα in an Hsp70 dose‐dependent manner.",
    "ncbi_link": "Siglec‐14: 100049587
Siglec‐5: 8778"
  },
  {
    "caption": "IL‐8 secretion was also evaluated after THP1Siglec‐5 and Siglec‐14cells were exposed to Hsp70. Similarly, only THP1Siglec‐14cells exhibited significant secretion of IL‐8 in an Hsp70 dose‐dependent manner.",
    "ncbi_link": "Siglec‐14: 100049587
Siglec‐5: 8778"
  },
  {
    "caption": "Western blot analysis demonstrates a greater increase in phosphorylated p38 (p‐p38) from THP1 Siglec‐14 cells after exposure to Hsp70 in comparison with control THP1 EV cells in a time‐dependent manner. Graph below immunoblots indicates densitometric analysis of each band normalized to the respective cell line's unstimulated control group, divided by the respective loading control.",
    "ncbi_link": "Siglec‐14: 100049587"
  },
  {
    "caption": "Exposure to Hsp70 also yielded greater degradation of the NF‐κB inhibitor, IκBα, in THP1 Siglec‐14 cells in comparison with control THP1 cells, augmentation of the pro‐inflammatory response. Graph below immunoblots indicates densitometric analysis of each band normalized to the respective cell line's unstimulated control group, divided by the respective loading control.",
    "ncbi_link": "Siglec‐14: 100049587"
  },
  {
    "caption": "Secretion of pro‐inflammatory cytokine IL‐8 by PMA‐differentiated THP1 EV or THP Sig 14 cells was evaluated by ELISA after concurrent exposure with an anti‐Hsp70 antibody or isotype‐matched antibody. Secretion of IL‐8 was decreased in only THP1 Sig 14 cells exposed to LPS and an anti‐Hsp70 antibody in comparison with the isotype control antibody, but this change was not observed in THP1 EV cells.",
    "ncbi_link": "Sig 14: 100049587"
  },
  {
    "caption": "TNFα secretion from SIGLEC14+/+ monocytes was measured after exposure to LPS or Hsp70 in the presence or absence of endotoxin‐neutralizing compound polymyxin B. Hsp70 was able to induce secretion of TNFα even in the presence of polymyxin B, suggesting a mechanism independent of endotoxin contaminants. DnaK, the E. coli homolog of human Hsp70, did not induce significant secretion of TNFα above background levels.",
    "ncbi_link": "SIGLEC14: 100049587"
  },
  {
    "caption": "TNFα secretion from SIGLEC14+/+ monocytes by Hsp70 was reduced when the cells were exposed to an anti‐Siglec‐5/Siglec‐14 blocking antibody.",
    "ncbi_link": "SIGLEC14: 100049587"
  },
  {
    "caption": "Human monocytes isolated from SIGLEC14+/+, SIGLEC14+/−, and SIGLEC14−/− individuals were exposed to varying concentrations of Hsp70, and TNFα secretion was evaluated. The amount of TNFα secreted was normalized to the respective cells' response to 1 ng/ml LPS to minimize the impact of other possible polymorphisms and factors that contribute to variation between individuals.",
    "ncbi_link": "SIGLEC14: 100049587"
  },
  {
    "caption": "TNFα secretion from SIGLEC14−/− monocytes stimulated with 15 ng/ml LPS and various concentrations of Hsp70. TNFα secretion was reduced with increasing concentrations of Hsp70.",
    "ncbi_link": "SIGLEC14: 100049587"
  },
  {
    "caption": "A HERC3 increases the protein levels of active YAP, p-YAP (S381), YAP and TAZ. active-YAP, p-YAP (S381), p-YAP (S127), YAP, p-TAZ (S89), TAZ, HERC3 and β-Actin were detected by Western blotting with appropriate antibodies as indicated in MDA-MB-231 cells stably expressing HERC3-WT or HERC3-CA. Ctrl, Control; WT, wildtype of HERC3; CA, HERC3-CA, a catalytically inactive mutant of HERC3.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "B HERC3 reverses the reduction in the active YAP and TAZ levels induced by serum starvation. MDA-MB-231 cells stably expressing HERC3 or HERC3-CA were cultured in medium with or without fetal bovine serum (FBS) for 1 h. Cells were harvested for Western blotting analysis with appropriate antibodies as indicated. Ctrl, Control; WT, wildtype of HERC3; CA, HERC3-CA, a catalytically inactive mutant of HERC3.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "C Depletion of HERC3 decreases the steady-state levels of YAP/TAZ. Levels of active-YAP, p-YAP (S381), p-YAP (S127), YAP, p-TAZ (S89), TAZ, HERC3 and β-Actin were detected by Western blotting with appropriate antibodies as indicated in MDA-MB-231 and SUM159 cells stably expressing shCtrl (Control shRNA), sh-1 and sh-2 (two shRNAs against HERC3).",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "E Depletion of HERC3 has no effects on mRNA levels of YAP/TAZ. Total mRNA levels of YAP/TAZ in control or HERC3-deficient MDA-MB-231 cells were analyzed by qRT-PCR using primers specific to YAP/TAZ. Data are shown as mean ±SEM; n = 3 biological replicates. Statistical analysis was performed using two-tailed Student t test. n.s., not significant.",
    "ncbi_link": "HERC3: 8916
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "G Depletion of HERC3 attenuates YAP- or TAZ-induced 8xGTIIC-Luc reporter activity. HEK293T cells were transfected with expression plasmids for YAP or TAZ, shHERC3 or shCtrl, and reporter plasmids 8xGTIIC-Luc and Renilla-Luc as indicated. Relative luciferase activity was measured as described in the text. Western blots showing expression of indicated proteins were shown. H Depletion of HERC3 attenuates YAP- or TAZ-induced CTGF-Luc reporter activity. Cell transfection and luciferase assay were carried out as described in Panel G. Western blots showing expression of indicated proteins were shown. Data are shown as mean ±SEM; n = 3 biological replicates. Statistical analysis was performed using two-tailed Student t test. **P < 0.01.",
    "ncbi_link": "Luc: 
HERC3: 8916
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "I Depletion of HERC3 attenuates transcription of YAP/TAZ target genes. Total mRNA levels of CTGF and ANKRD1 in control or HERC3-deficient MDA-MB-231 cells were analyzed by qRT-PCR using primers specific to the indicated target gene. Data are shown as mean ±SEM; n = 3 biological replicates. Statistical analysis was performed using two-tailed Student t test. ***P < 0.001.",
    "ncbi_link": "ANKRD1: 27063
CTGF: 1490
HERC3: 8916"
  },
  {
    "caption": "A HERC3 and HERC3-CA block β-TrCP-mediated degradation of TAZ. HEK293T cells were transfected with expression plasmids for HA-β-TrCP, Myc-HERC3 or Myc-HERC3-CA, FLAG-TAZ or FLAG-GFP as indicated. Cells were harvested 24 h post-transfection. Protein levels were detected by Western blotting with appropriate antibodies as indicated.",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
Myc: 
β-TrCP: 8945
HERC3: 8916
TAZ: 6901"
  },
  {
    "caption": "D HERC3 and HERC3-CA extend the half-life of TAZ. Control or HERC3-deficient MDA-MB-231 cells were treated with cycloheximide (CHX, 20 µM) for 0, 4, 8 or 12 h before harvested. Left, Western blotting with appropriate antibodies. Right, Image J quantitation of YAP intensity and normalized to β-Actin at the indicated time points (n = 3 biological replicates). Data are represented as the mean ± SEM (right panel).",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "F Depletion of HERC3 decreases the half-life of YAP/TAZ. Control or HERC3-deficient MDA-MB-231 cells were treated with cycloheximide (CHX, 20 µM) for 0, 2, 4 or 6 h before harvested. Left, Western blotting with appropriate antibodies. Right, Image J quantitation of YAP intensity and normalized to β-Actin at the indicated time points (n = 3 biological replicates). Data are represented as the mean ± SEM (right panel).",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "G Depletion of β-TrCP reverses shHERC3-induced degradation of YAP/TAZ. Control or HERC3-deficient MDA-MB-231 were transfected with siCtrl or siβ-TrCP as indicated. Cells were harvested 48 h post-transfection. Protein levels were detected by Western blotting with appropriate antibodies as indicated.",
    "ncbi_link": "β-TrCP: 8945
HERC3: 8916"
  },
  {
    "caption": "A HERC3 interacts with β-TrCP, but not YAP or TAZ. HEK293T cells were transfected with expression plasmids for FLAG-HERC3, HA-YAP or HA-TAZ or HA-β-TrCP. Cells were harvested 24 h post-transfection and subjected to IP with FLAG antibody-conjugated agarose beads. Protein levels were detected by Western blotting with HA and FLAG antibodies. B HERC3 interacts with endogenous β-TrCP. MDA-MB-231 cells stably expressing HERC3 or HERC3-CA were harvested and subjected to IP with IgG or HA antibodies. Protein levels were detected by Western blotting with β-TRCP, HA and β-Actin antibodies. C",
    "ncbi_link": "FLAG: 
HA: 
β-TrCP: 8945
HERC3: 8916
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "H HERC3 blocks the interaction between β-TrCP and YAP. HEK293T cells were transfected with expression plasmids for FLAG-YAP, HA-β-TRCP, Myc-HERC3 and Myc-HERC3-CA as indicated. Cells were harvested 24 h post-transfection and subjected to IP with FLAG antibody-conjugated agarose beads. Protein levels were detected by Western blotting with HA, FLAG and Myc antibodies.",
    "ncbi_link": "FLAG: 
HA: 
Myc: 
β-TRCP: 8945
HERC3: 8916
YAP: 10413"
  },
  {
    "caption": "A Depletion of HERC3 reduces cell proliferation. Control or HERC3-deficient MDA-MB-231 were analyzed for indicated days by CCK8 assay as described in the materials and methods. Data are shown as mean ± SEM; n = 3 biological replicates.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "C Depletion of HERC3 inhibits colony formation in MDA-MB-231 cells. Control or HERC3-deficient MDA-MB-231 were analyzed by colony formation assay. Quantification of the results in colony formation assays was analyzed by Image J. D Depletion of HERC3 inhibits colony formation in SUM159 cells. Control or HERC3-deficient SUM159 were analyzed by colony formation assay. Quantification of the results in colony formation assays was analyzed by Image J.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "Depletion of HERC3 attenuates cell migration. Control or HERC3-deficient MDA-MB-231 cells (upper panel) and SUM159 cells (lower panel) were analyzed by transwell migration assay. E, migrated were fixed in 4% PFA and stained with 0.1% crystal violet and photographed. data quantification of migrated MDA-MB-231 cells (left panel) and SUM159 (right panel) cells counts by Image J.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "H RNAi-resistant HERC3 and YAP/TAZ mutants reverse the inhibitory effect of HERC3 depletion on colony formation. Ectopic expression of RNAi-resistant HERC3-WT, HERC3-CA and YAP/TAZ mutants in HERC3-deficient MDA-MB-231 cells were subjected to colony formation assay as described in Panel C.",
    "ncbi_link": "HERC3: 8916
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "I, J RNAi-resistant HERC3 and YAP/TAZ mutants reverse the inhibitory effect of HERC3 depletion on cell migration. I, ectopic expression of resistant variants of HERC3-WT, HERC3-CA and YAP/TAZ mutants in HERC3-deficient MDA-MB-231 cells were subjected to transwell migration assay. Scale bar, 100 μm. J, graphic representation of quantitated cell migration in Panel I.",
    "ncbi_link": "HERC3: 8916
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "HERC3 knockdown inhibits breast tumorigenesis. Luciferase-harboring MDA-MB-231 cells expressing shHERC3 or shCtrl were subcutaneously injected into 5-week-old nude mice. Four weeks after injection, mice were monitored by bioluminescence using Xenogen IVIS imaging system. A, representative tumors expressing luciferase are indicated by radiance bar (p/sec/cm2/sr). B, quantitation of bioluminescence data. Data are shown as mean ±SEM; n = 6 biological replicates. Statistical analysis was performed using two-tailed Student t test. **P < 0.01, ***P < 0.001.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "J, K shHERC3 attenuates breast cancer lung metastasis. Mice were injected with control or HERC3-deficient MDA-MB-231 cells. J, Bright-field images (upper panel, scale bars, 2 mm) and H&E staining (lower panel, scale bars, 50 μm) of the lungs from mice. K, number of lung metastasis nodules. Data are shown as mean ±SEM; n = 5 biological replicates. Statistical analysis was performed using two-tailed Student t test. ***P < 0.001.",
    "ncbi_link": "HERC3: 8916"
  },
  {
    "caption": "RNAi-resistant HERC3 and unphosphorylatable YAP-S381A can counteract the tumor suppressive effect of HERC3 depletion. HERC3-deficient cells with or without ectopic expression of YAP-S381A, RNAi-resistant variants of HERC3-WT or HERC3-CA and control MDA-MB-231 cells were performed subcutaneously injection as described in Panel A. L, tumors were dissected and photographed at four weeks after cell implantation. M, volume from all tumors was recorded.",
    "ncbi_link": "HERC3: 8916
YAP: 10413"
  },
  {
    "caption": "(B) Representative images of core, edge and adjacent non-tumour brain tissue for Iba1, p-S6 and DAPI staining in Pten-/-p53-/- (right) and GL261 (left) tumours. Percentage of Iba1+ cells co-expressing p-S6 in the three defined regions. Five high grade glioma models were analysed - GL261 (n=3), PDGFB (n=3), Ntv-a;PDGFB+shp53 (n=2), Pten-/-p53-/- (n=3), and Pten-/-p53-/-Idh1mut (n=3) (mean ±SEM; Two-Way ANOVA Tukey test).",
    "ncbi_link": "Idh1: 15926
Ntv-a: 10763
Pten: 19211
p53: 22059"
  },
  {
    "caption": "(F,G) Expression levels of (F) Rps6 and (G) Eif4ebp1 in healthy versus GL261 microglia and macrophage (n=3; mean ±SEM, likelihood ratio test in edgeR).",
    "ncbi_link": "Eif4ebp1: 13685
Rps6: 20104"
  },
  {
    "caption": "Signalling was analysed in microglia by immunoblotting of whole cell lysates collected at 4hr (B and normalised against non-phosphorylated protein and vinculin analysed on the same blot. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Flow cytometry analysis was carried out in microglia for (C) p-S6 S240/244 Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Signalling was analysed in microglia by immunoblotting of whole cell lysates collected at 4hr and normalised against non-phosphorylated protein and vinculin analysed on the same blot. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Flow cytometry analysis was carried out in microglia for (E) p-4EBP1 T37/46 Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Signalling was analysed in microglia by immunoblotting of whole cell lysates collected at 4hr and normalised against non-phosphorylated protein and vinculin analysed on the same blot. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Flow cytometry analysis was carried out in microglia for (G) p-AKT S473; Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+Torin, was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Signalling was analysed in microglia by immunoblotting of whole cell lysates collected at 0.5hr (H) and normalised against non-phosphorylated protein and vinculin analysed on the same blot. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM +LY) was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "Flow cytometry analysis was carried out in microglia for (I) p-AKT T308. Each treatment (mNSC-CM, Pten-/-p53-/- mGIC-CM, Pten-/-p53-/- mGIC-CM+ LY) was normalised to unconditioned control (n=3; mean ±SEM, Two-Way ANOVA Tukey test). *p≤0.05, **p≤0.01, ***p≤0.001 comparing mGICPten-/-;p53-/--CM versus mGICPten-/-;p53-/--CM +inhibitor.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "(B) Survival analysis for Cx3cr1-Rheb1Δ/Δ (n=7) and Rheb1fl/fl (n=7) mice. Chi square test.",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(C) Representative images and quantification of the tumour volume with MRI of Rheb1fl/fl (n=8) compared to Cx3cr1-Rheb1Δ/Δ (n=8) mice. (mean ±SEM; Unpaired parametric t test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(D) H&E staining showing representative histological features (overview and high magnification of microvascular proliferation) of Rheb1fl/fl and Cx3cr1-Rheb1Δ/Δ GL261 tumours. Scale bar is 125 μm (top, H&E) and 80 μm (all other images)",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(E) Percentage of GFP+ CD45- GL261 tumour cells in Cx3cr1-Rheb1Δ/Δ (n=5) and Rheb1fl/fl (n=7) tumours, with representative FACS plot (mean ±SEM; Unpaired parametric t test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(B) Levels of TAM-MG (P2RY12+ CD49d-) and TAM-BMDM (P2RY12- CD49d+) gated from CD45+ population in GL261 tumours from Rheb1fl/fl (n=4) and Cx3cr1-Rheb1Δ/Δ (n=5) mice by flow cytometry (representative flow cytometry plots on top and quantification at the bottom; mean ±SEM; Two-Way ANOVA Tukey test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(C) Percentage of CD8 CTL (top) and CD4 Th (CD4) cells in GL261 tumours from Rheb1fl/fl (n=4) and Cx3cr1-Rheb1Δ/Δ (n=5) mice assessed by flow cytometry (representative flow cytometry plots, left and quantification, right; mean ±SEM; Unpaired t test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(D) Tumour tissues from Rheb1fl/fl (n=4) and Cx3cr1-Rheb1Δ/Δ (n=4) were stained for CD8, CD4 and FoxP3. DAB staining was quantified as % of positive cells using Definiens software. Representative images of the stained tissues are shown. (mean ±SEM; unpaired parametric t test). Scale bar is 100µm.",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(B) Heatmap of the differential correlation analysis between CIBERSORT cell fractions and signatures enrichment scores (ssGSEA) for lymphocytes in the Cx3cr1-Rheb1Δ/Δ (n=3) vs Rheb1fl/fl (n=3) GL261 tumours.",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(C,D) CD4 Th cells (C) and CD8 CTL cells (D) expression of Ki67, perforin, granzyme b, and IFNγ, in Cx3cr1-Rheb1fl/fl (n=5) and Rheb1Δ/Δ (n=5) GL261 tumours. Representative FACS plots show control samples (tumour-derived cells stimulated in culture in the absence of protein inhibitor cocktail - in orange) compared to stimulated cells derived from Rheb1fl/fl (fl/fl, red) and Cx3cr1-Rheb1Δ/Δ (Δ/Δ, blue) GL261 tumours (cells stimulated in culture with protein inhibitor cocktail) (mean ±SEM; Two-Way ANOVA Tukey test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(E,F) Expression of CD44 (E) and CD62L (F) by CD4 Th and CD8 CTL in Cx3cr1-Rheb1fl/fl (n=5; fl/fl, red) and Rheb1Δ/Δ (n=5; Δ/Δ, blue) GL261 tumours with representative FACS plots show control samples (mean ±SEM; Two-Way ANOVA Tukey test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(E) Microglia were pre-treated with Torin, or medium as indicated and then stimulated with mNSC-CM, mGICPten-/-;p53-/--CM, or GL261-CM. p-NF-ĸB (p-P65) and p-STAT3 were analysed by immunoblotting of whole cell lysates collected at 4hr.",
    "ncbi_link": "Pten: 19211
p53: 22059"
  },
  {
    "caption": "(G) Production of Il-12 (Il-12p40), Tnf, Il6, and Il10 by conditioned microglia was determined by qPCR. Each treatment was normalised to housekeeping gene and the unconditioned control. (n=3; mean ±SEM; Two-Way ANOVA Tukey test).",
    "ncbi_link": "Il10: 16153
Il-12: 16160
Il6: 16193
Tnf: 21926"
  },
  {
    "caption": "(H,I) MFI levels of pSTAT3 in TAM-MG (CD45+ P2RY12+ CD49d-) (H) and p-NF-κB (p-P65) in TAM-BMDM (CD45+ P2RY12- CD49d+) (I) from Rheb1fl/fl (fl/fl, blue, n=4) and Cx3cr1-Rheb1Δ/Δ (Δ/Δ, red, n=5) GL261 tumours. Representative FACS plots are displayed for each cell type (mean ±SEM, Two-Way ANOVA Tukey test).",
    "ncbi_link": "Cx3cr1: 13051
Rheb1: 19744"
  },
  {
    "caption": "(A) Correlation between ssGSEA enrichment scores for the mTOR signature versus TAM-MG or TAM-BMDM signatures in TCGA GBM transcriptomic data. Comparison carried out on all IDH-wild-type samples, and in a subgroup specific manner according to Wang's classifier. Size of circle is indicative of Rsquare value and bold outline represents a p-value ≤0.05.",
    "ncbi_link": "IDH: "
  },
  {
    "caption": "(B) Separation of IDH-wildtype GBM samples between those displaying high mTOR and microglia enrichment (+ve correlation, group 1 in orange) and those without this signature (group 2 in green).",
    "ncbi_link": "IDH: 3418///3417"
  },
  {
    "caption": "(C) CIBERSORT cell fractions calculated from the TPM of TCGA IDH-wild type GBM samples from group 1 compared to those from group 2.",
    "ncbi_link": "IDH: 3418///3417"
  },
  {
    "caption": "G,  Tumour volume (measured by ultrasound) of CTL and THEM6 KO 22rv1-derived orthografts developed in surgically castrated  mice. H, Tumour volume of CTL and THEM6 KO  LNCaP  AI-derived  xenografts developed in surgically castrated  mice. I, Tumour volume  (measured by ultrasound) of CTL and THEM6  KO CWR22res-derived orthografts. Orchidectomy was performed 3-weeks after cell implantation. Data information: Data are presented as mean values +/- SD. Statistical analysis: G, H: two-tailed Mann-Whitney U test. I: Kruskal-Wallis test. Data reproducibility: G, I: n = 5  mice per group. Panel H: n = 7 mice per group.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "B-C, Changes in lipid content (total amount) observed in THEM6  KO CRPC cells when compared to CTL. Data information: Data are presented as mean values +/- SD. Statistical analysis : *p-value < 0.05 using a 1-way ANOVA with a Dunnett's multiple comparisons test. Data reproducibility: n = 3 independent biological experiments. DAG: diacylglycerol; TG: triglyceride;  PC: phosphatidylcholine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; LysoPC: lysophosphatidylcholine; LysoPE: lysophosphatidylethanolamine;  Cer: Ceramide; SM: sphingomyelin; CE: Cholesteryl ester.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "C, Representative electron microscopy (EM) pictures of CTL and  THEM6 KO 22rv1  cells taken at low (left) and high (right) magnification. Red arrows point towards abnormal  ER structure. Scale bar represents 500 nm.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "J, Western blot  analysis of CALX and  CALR expression in PCa cells following THEM6 silencing. Data information: Data reproducibility: representative image from 3 independent biological experiments.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "B, RT-qPCR analysis of MVD,  FDPS and  DHCR7 expression in CTL and  THEM6 KO 22rv1 cells. CASC3  was used as a normalising control. Data information: Data are presented as mean values +/- SD. Statistical analysis: : *p-value < 0.05 using 1-way ANOVA with a Dunnett's multiple comparisons test. Data reproducibility: : n = 3 independent biological experiments.",
    "ncbi_link": "CASC3: 22794
DHCR7: 1717
FDPS: 2224
MVD: 4597
THEM6: 51337"
  },
  {
    "caption": "F, Labelled cholesterol fraction derived from  13C-glucose and 13C-glutamine  in CTL and THEM6 KO CWR22res cells after 72 hours of incubation. G, Labelled cholesterol fraction derived from 13C-glucose  and 13C-glutamine  in CTL and THEM6 KO MCF-7 cells after 72 hours of incubation. Data information: Data are presented as mean values +/- SD. Statistical analysis: , F, : *p-value < 0.05 using 1-way ANOVA with a Dunnett's multiple comparisons test. G: *p-value < 0.05 using a two-tailed Student t-test. Data reproducibility: : n = 3 independent wells from the same cell culture.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "J, Labelled palmitic, oleic and stearic acid  fractions derived from 13C-glucose and 13C-glutamine in CTL and THEM6 KO  22rv1  cells after 72 hours of incubation. Data information: Data are presented as mean values +/- SD. Statistical analysis: : *p-value < 0.05 using 1-way ANOVA with a Dunnett's multiple comparisons test. Data reproducibility: n = 3 independent wells from the same cell culture.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "B, Proteomic  analysis highlighting proteins associated with the  ER stress response significantly down-regulated in THEM6 KO 22rv1 cells when compared to CTL (p-value ≤ 0.05, FC = 1.3). Data information: Data are presented as mean values +/- SD. Data reproducibility: n = 3 independent biological experiments.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "E, Proteomic  analysis highlighting ATF4 targets significantly down-regulated in THEM6  KO LNCaP AI cells when compared to CTL (p-value ≤ 0.05, FC = 1.3). Data information: Data are presented as mean values +/- SD. Data reproducibility: n = 3 independent biological experiments.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "J, Western blot  analysis of ATF4 and CHOP expression  in CTL and THEM6 KO LNCaP AI cells treated with palmitic acid (200 µM) or hexadecylglycerol (50 µM) for 48 hours. Data information: HSC70  was used as a sample loading control. Data reproducibility: representative image from 3 independent biological experiments.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "M, Volcano plot of the differentially modulated genes in  PCa patients from the PRAD TCGA stratified according to THEM6 expression. Red dots represent the UPR-related genes extracted from the UPR-gene signature Data information: Data reproducibility: n = 489 tumours.",
    "ncbi_link": "THEM6: 51337"
  },
  {
    "caption": "(B) Depletion of FTCD by FTCD siRNA duplexes. HepG2 cells were either mock transfected with water or transfected with two distinct siRNA duplexes specific to FTCD. After incubation for 48 hrs, the cells were analyzed by Western blotting with antibodies to FTCD and α-tubulin.",
    "ncbi_link": "FTCD: 10841"
  },
  {
    "caption": "(C) The Golgi in cells which were depleted of either FTCD or p47. HepG2 cells, which were treated with either FTCD siRNAs, p47 siRNA or mock for 48 hrs, were fixed and stained with a monoclonal antibody to GM130. Scale bar = 10 μm. (D) The results of quantification of (C). The values are from five sets of independent experiments. Results are expressed as the mean±SD (n=5), with 100 cells counted in each group of each set. Asterisks indicate a significant difference at P<0.01 compared with the mock-treated cells (Bonferroni method). ",
    "ncbi_link": "FTCD: 10841
p47: 55968"
  },
  {
    "caption": "(E) Representative EM images of the Golgi in HepG2 cells treated with either mock or FTCD siRNAs for 42 hrs. Scale bar = 0.5 μm. (F) The results of quantification of (E). Golgi membranes in HepG2 cells were classified into cisternae, vesicles and tubules, and counted as previously described (Shorter & Warren, 1999). The results are shown as the mean±SD of five sets of independent experiments, with 15-20 cells counted in each group in each independent experiment. An asterisk indicates a significant difference (P<0.05) compared with the mock-treated cells in each category (Bonferroni method). ",
    "ncbi_link": "FTCD: 10841"
  },
  {
    "caption": "(B) The effects of FTCD siRNA treatment on Golgi reassembly at the end of mitosis. HepG2 cells were treated with either FTCD siRNA (FTCD siRNA 2 duplex) or mock for 48 hrs before the collection of mitotic cells. The collected mitotic cells were cultured for 35 mins and then fixed. The cells were stained with a polyclonal antibody to GM130 and a monoclonal antibody to α-tubulin, and observed by confocal microscopy. Panels a-p display representative images. Scale bar = 10 μm.",
    "ncbi_link": "FTCD: 10841"
  },
  {
    "caption": "(C) Rescue experiments in FTCD siRNA-treated HepG2 cells. The indicated HA-tagged FTCDs, which were insensitive to FTCD siRNA, were expressed 25 hrs after the treatment of cells with FTCD siRNA2. The cells were further cultured for 23 hrs and then used for the collection of mitotic cells. The collected mitotic cells were cultured for 35 mins and fixed. The cells were stained with a monoclonal antibody to α-tubulin (panels g and h) and polyclonal antibodies to GM130 and HA (panels a-f). Scale bar = 10 μm.",
    "ncbi_link": "FTCD: 10841"
  },
  {
    "caption": "(A) p47 requires its association with FTCD for its localization to the Golgi at the end of mitosis. HepG2 cells were treated with FTCD siRNA and then the indicated HA-tagged FTCDs were expressed as described in Figure 4C. The mitotic cells were collected, cultured for 35 mins, and then fixed. The cells were stained with polyclonal antibodies to p47 and HA and a monoclonal antibody to GM130, and observed by confocal microscopy. Panels a-l show the distribution of p47 or/and GM130 and panels m-o show HA-FTCD expression. Scale bar = 10 μm. (B) Insets in (A). p47 (red) and the GM130 (a Golgi marker, green) were visualized. Scale bar = 5 μm. (C) The results of quantification of (A). The results are shown as the mean±SD of five sets of independent experiments, with 100 cells counted in each group in each independent experiments. Asterisks indicate a significant difference at P<0.01 compared with the mock-treated cells (Bonferroni method). ",
    "ncbi_link": "FTCD: 10841"
  },
  {
    "caption": "(A) The expression of FTCDwt-HA-MAO causes the aggregation of mitochondria. HeLa Tet-off cells inducibly expressing either FTCDwt-HA-MAO or FTCD(R382A)-HA-MAO were cultured in DOX-free medium for 48 hrs. Cells which were cultured in the DOX-containing medium were used as a control. The cells were fixed and stained with a monoclonal antibody to mitochondria and a polyclonal antibody to HA, followed by observation by confocal microscopy. Panels a-j display representative images. Scale bar = 10 μm. (B) The results of quantification of (A). Results are shown as the mean±SD of five sets of independent experiments, with 100 cells counted in each group in each independent experiment. An asterisk indicates a significant difference at P<0.01 compared with the others (Bonferroni method). ",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128"
  },
  {
    "caption": "(C) Representative EM images of a cell expressing FTCDwt-HA-MAO. The HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO were cultured for 48 hrs in the absence of DOX, and used for EM observation. Panel b displays the inset in panel a. Arrowheads show narrow gaps between mitochondria. Scale bar = 0.2 μm. The low magnification image is presented in Figure EV2C.",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128"
  },
  {
    "caption": "(D) Endogenous p47 and p97 are necessary for mitochondria aggregation mediated by FTCDwt-HA-MAO. HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO were transfected with either mock, p47 siRNA or p97 siRNA duplexes and cultured for 24 hrs. The cells were further cultured in DOX-free medium for 48 hrs for the induction of FTCDwt-HA-MAO, and then analyzed as in (A). Panels a-l display representative images. Scale bar = 10 μm. (E) The results of quantification of (D). Results are shown as the mean±SD of five sets of independent experiments, with 100 cells counted in each group in each independent experiment. An asterisk indicates a significant difference at P<0.01 compared with the others (Bonferroni method). ",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128
p47: 55968
p97: 7415"
  },
  {
    "caption": "(F) Binding between FTCD and p47 and between p47 and p97 is necessary for mitochondria aggregation mediated by FTCDwt-HA-MAO. The HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO were transfected with mammalian expression constructs of siRNA-insensitive Flag-tagged p47wt/mutants at the same time as the treatment of p47 siRNA, and cultured for 24 hrs. The cells were further cultured in DOX-free medium for 48 hrs for the induction of FTCD-HA-MAO. After fixation, the cells were visualized with a monoclonal antibody to mitochondria and polyclonal antibodies to HA and Flag. Panels a-l display representative images. Scale bar = 10 μm. (G) Binding between FTCD and p97 is necessary for mitochondria aggregation mediated by FTCDwt-HA-MAO. The HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO were transfected with the mammalian expression construct of siRNA-insensitive Flag-tagged p97wt/mutant at the same time as treatment with p97 siRNA. The following procedures were the same as in (F). Panels a-i display representative images. Scale bar = 10 μm. (H) The results of quantification of (F) and (G). Results are shown as the mean±SD of five sets of independent experiments, with 100 cells counted in each group in each independent experiment. Asterisks indicate a significant difference at P<0.01 compared with siRNA treatment alone ('none') and compared with mutant expression (Bonferroni method). ",
    "ncbi_link": "Flag: 
HA: 
FTCD: 10841
MAO: 4129///4128
p47: 55968
p97: 7415"
  },
  {
    "caption": "(A) FTCD located in mitochondria causes mitochondria aggregation during mitosis. Mitotic cells were collected by flushing from HeLa Tet-off cells in which either FTCDwt-HA-MAO or FTCD(R382A)-HA-MAO had been induced for 24 hrs. The mitotic cells were further cultured for 4 hrs to enable complete cytokinesis. Cells in which FTCDwt-HA-MAO was induced for 28 hrs without synchronization were used as the asynchronous control group. Cells were fixed and visualized with a monoclonal antibody to mitochondria and a polyclonal antibody to HA. Panels a-f display representative images. Scale bar = 10 μm. (B) The results of quantification of (A). Results are shown as the mean±SD of seven sets of independent experiments, with 100 cells counted in each group in each independent experiment. An asterisk indicates a significant difference at P<0.01 compared with the others (Bonferroni method). ",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128"
  },
  {
    "caption": "(C) A single living cell expressing FTCDwt-HA-MAO was tracked during mitosis. Mitotic cells were collected by flushing from the HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO, and cultured in the absence or presence of DOX. The cells were stained with MitoTracker at the 22 hr time point and confocal images of 30-40 cells were randomly taken at the 23 hr time point. From the 23 hr to 27 hr time point, cells were tracked in the bright field every 30 mins. At the 27 hr time point, confocal images were taken of the 21-38 cells that were successfully tracked. Panels a-j display representative images. Asterisks indicate the tracked cells. Scale bar = 10 μm. (D) The results of quantification of (C). The experiment was repeated five times and each line shows the average percentage of an independent experiment. The percentages of cells that underwent mitosis are as follows: 41.5 % in the DOX(-) group and 54.7 % in the DOX(+) group. ",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128"
  },
  {
    "caption": "(E) FTCD located in mitochondria causes mitochondria aggregation at the end of mitosis. Mitotic cells were collected from the HeLa Tet-off cells inducibly expressing FTCDwt-HA-MAO and cultured in the absence or presence of DOX as in (C). Cells were stained with MitoTracker at the 23hr time point and observed by confocal microscopy from the 24 hr to 26 hr time point. Panels a-t display representative images. Scale bar = 10 μm.",
    "ncbi_link": "HA: 
FTCD: 10841
MAO: 4129///4128"
  },
  {
    "caption": "E) Plaque assays were performed similarly as described for (a) with Pru WT (n=20 for plaque number and n=7 for plaque area), PruΔgra15 (n=20 for plaque number and n=7 for plaque area), PruΔgra15+GRA15 complemented (n=12 for plaque number and n=7 for plaque area).",
    "ncbi_link": "gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "F) Plaque assays were performed similarly as described for (A) with RH (n=5 for plaque number and n=3 for plaque area) and RH+GRA15II (n=5 for plaque number and n=3 for plaque area).",
    "ncbi_link": "GRA15II: 7895856"
  },
  {
    "caption": "G) Relative parasite growth was measured as described in (B) with Pru WT (n=12), PruΔgra15 (n=12), PruΔgra15+GRA15 complemented (n=8).",
    "ncbi_link": "gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "H) Number of PVs was calculated as described in (C) with Pru WT (n=3), PruΔgra15 (n=3), RH (n=3) and RH+GRA15II (n=3) and normalized with the number of host cells in each field.",
    "ncbi_link": "gra15: 7895856
GRA15II: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (A) Total ubiquitin (n=3 for RH, n=5 for Pru and n=3 for PruΔgra15), is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (B) K63-linked ubiquitin (n=3 for RH, n=3 for Pru and n=3 for PruΔgra15), is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (C) p62 (n=3 for RH, n=10 for Pru and n=7 for PruΔgra15, n=4 for Pru Δgra15+GRA15), is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (D) NDP52 (n=3 for RH, n=3 for Pru and n=3 for PruΔgra15), is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (E) LC3B (n=3 for RH, n=3 for Pru and n=3 for PruΔgra15, n=3 for Pru Δgra15+GRA15), is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (F) GABARAP (n=3 for RH, n=3 for Pru and n=3 for PruΔgra15) is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "HFFs were stimulated with for 24 h with 10U/mL IFNγ or left unstimulated and subsequently infected with RH, Pru or PruΔgra15 parasites for 3 h. The percentage of vacuoles that stained positive for (G) LAMP1 (n=3 for RH, n=3 for Pru and n=3 for PruΔgra15) is shown in the left bar diagram. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as inset pictures with magnification.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "B) Nuclear translocation of the NF-κB p65 subunit was quantified in HFFs or HFFs treated with BAY11-7082 (1µM, added 2 h pre-infection) 24 h p.i. with Pru parasites. Experiments were done 4 times where each dot represents one experimental mean of at least 15 nuclei. In the right panel, representative images are shown. Parasites were expressing GFP, nuclei are stained with Hoechst 33258. Scale bar is 20 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "C) Immunoprecipitation and Western blot were performed in HFFs with and without IFNγ (10 U/ml) using an RH strain expressing type II GRA15-HA and as a control RH expressing GRA35-HA. The blots using antibodies against TRAF2 and TRAF6 were made after stripping the first blot. The inputs loaded represent 1% of total lysate prepared for immunoblotting and mass spec (Table EV1). The antibodies against TRAF2 and TRAF6 were obtained from Santa Cruz Biotechnology (Appendix Table S2). Full length blots for this figure can be observed in the source data for this figure.",
    "ncbi_link": "GRA35: 
HA: 
type II GRA15: 7895856"
  },
  {
    "caption": "D) Immunoprecipitation and Western blot were performed in HFFs with and without IFNγ (10 U/ml) using an RH strain expressing type II GRA15-HA and as a control RH expressing GRA43-HA. The blots using antibodies against TRAF6 were made after stripping the first blot that is used for HA blotting. The inputs loaded represent 10% of total lysate prepared for immunoblotting. Following TRAF6 blotting, the membrane was stripped and blotted for TNFAIP3.",
    "ncbi_link": "GRA43: 
HA: 
type II GRA15: 7895856"
  },
  {
    "caption": "E) Immunofluorescence analysis of TRAF6 recruitment to the PVM of HFFs infected for 3 h with RH, Pru and PruΔgra15 strains. On the right-hand side, a representative fluorescent image is shown of TRAF6 recruitment to the PVM where Toxoplasma Pru strain expresses GFP, DNA was stained with Hoechst 33258. Scale bar is 10 µm. n=3 for all the strains. The antibody against TRAF6 was purchased from Abnova (Appendix Table S2).",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "F) Immunoprecipitation and Western blot were performed in HFFs with and without IFNγ (10 U/ml) using a RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut. For the unstimulated cells, uninfected HFFs were used an additional negative control (left panel). Left panel and right panel were run on a single gel; vertical white lines indicate excision of irrelevant lanes. Full length blots are in the source data for this figure. The antibodies used against TRAF2 and TRAF6 were purchased from Cell Signaling Technology and Abnova, respectively. The asterisks (*) in the lower right panel indicates the faint band of TRAF6 in the RH+GRA15TRAF2mut immunoprecipitate.",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of p62, with and without IFNγ in RH, RH+GRA15WT. All the experiments were done 3 times with each of the strains.",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of LC3B with and without IFNγ in RH, RH+GRA15WT. All the experiments were done 3 times with each of the strains.",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of LAMP1 with and without IFNγ in RH, RH+GRA15WT. All the experiments were done 3 times with each of the strains.",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "J) Plaque assays were performed with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "K) Expression of TRAF6 was detected by Western blotting of lysates from scrambled siRNA transfected and TRAF6-specific siRNA transfected HFFs with and without IFNγ.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "L) Relative parasite growth was measured in scrambled siRNA transfected HFFs and TRAF6 knockdown HFFs using luciferase-based assay with indicated strains with and without IFNγ (n=3). The antibody against TRAF6 used here was from Abcam (Appendix Table S2). Full length blots are in supplementary figures 4l-m.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "Immunofluorescence analysis of p62 was done in scrambled siRNA transfected HFFs and TRAF6 knockdown HFFs with and without IFNγ using indicated strains (n=3).",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "Immunofluorescence analysis of LC3B was done in scrambled siRNA transfected HFFs and TRAF6 knockdown HFFs with and without IFNγ using indicated strains (n=3).",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (A) IRGB6 For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (B) GBPs, For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (C) total ubiquitin, For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (D) K63-linked ubiquitin, For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (E) K48-linked ubiquitin For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "MEFs were stimulated with IFNγ for 24 h (100 U/ml). IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 or RH for 3 h and subsequently fixed, permeabilized and stained for (F) LC3B. For analysis, at least 100 vacuoles were scored. All experiments were performed 3 times. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. All experiments were performed 3 independent times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "G) MEFs were stimulated with IFNγ for 24 h (100 U/ml) or left unstimulated and subsequently infected with Pru, PruΔgra15 and GRA15 complemented parasites for 24 h for measuring parasite growth by luciferase assay. All experiments were performed 3 independent times.",
    "ncbi_link": "gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "H) Plaque numbers were measured for Pru (n=12), PruΔgra15 (n=12) and GRA15 complemented parasites (n=6).",
    "ncbi_link": "gra15: 7895856
GRA15: 7895856"
  },
  {
    "caption": "I-J) MEFs were stimulated with IFNγ for 24 h (100 U/ml) or left unstimulated and subsequently infected with RH or RH expressing type II GRA15. Plaque numbers were counted (n=3), and areas were measured 4 days p.i. (n=3).",
    "ncbi_link": "type II GRA15: 7895856"
  },
  {
    "caption": "A) Immunoprecipitations and Western blots were performed on MEFs stimulated or not with IFNγ (100 U/ml) and infected with an RH strain expressing type II GRA15-HA and as a control RH expressing GRA45-HA. The blots using antibodies against TRAF6 and TRAF2 were made after stripping the first blot. Left panel and right panel were run on a single gel; vertical white lines indicate excision of irrelevant lanes.",
    "ncbi_link": "GRA45: 
HA: 
type II GRA15: 7895856"
  },
  {
    "caption": "B) IFNγ-stimulated MEFs were infected with Pru, PruΔgra15 and RH for 3 h and subsequently stained for TRAF6. On the right-hand side, a representative fluorescent image is shown for the Toxoplasma Pru strain, which expresses GFP. DNA was stained with Hoechst 33258. Scale bar is 10 µm. The yellow box inside each representative image is shown as an inset picture with magnification. Experiments were performed 3 times.",
    "ncbi_link": "GFP: 
gra15: 7895856"
  },
  {
    "caption": "C) IRGB6 staining on PVM after infection of wild-type or Traf6 -/- MEFs for 3 h with Pru, PruΔgra15 and RH. On the right-hand side, a representative fluorescent image is shown of IRGB6 coating on the PVM of both wild-type and Traf6 -/- MEF. Scale bar is 10 µm. At least 100 different vacuoles were observed and analyzed for each experiment (n=3).",
    "ncbi_link": "gra15: 7895856
Traf6: 22034"
  },
  {
    "caption": "D) Parasite growth was measured 24 h p.i. using luciferase readout from unstimulated and IFNγ-stimulated wild-type, NFκB p65-/- and Traf6 -/- MEFs. Growth was compared between Pru, PruΔgra15 and PruΔgra15+GRA15 (complemented) strains. Reading from unstimulated cells was considered as 100% and percentage growth in IFNγ-stimulated cells was expressed relative to unstimulated cells. Experiments were performed three times with each MEF type.",
    "ncbi_link": "gra15: 7895856
GRA15: 7895856
NFκB p65: 19697
Traf6: 22034"
  },
  {
    "caption": "E) Immunoprecipitation and Western blot were performed in MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut and as a control RH expressing GRA45-HA. Left panel and right panel were run on a single gel; vertical white lines indicate excision of irrelevant lanes. Full length blots are in the source data for this figure. The antibodies used against TRAF2 and TRAF6 were purchased from Cell Signaling Technology and Abnova, respectively.",
    "ncbi_link": "GRA45: 
HA: 
GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of TRAF6, was done in IFNγ-stimulated MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of IRGB6, was done in IFNγ-stimulated MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of GBP1-5, was done in IFNγ-stimulated MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of p62 was done in IFNγ-stimulated MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "Immunofluorescence analysis of ubiquitin was done in IFNγ-stimulated MEFs infected with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=3).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "K) Plaque assays were performed with RH+GRA15WT, RH+GRA15TRAF2mut or RH+GRA15TRAF2/6mut (n=4).",
    "ncbi_link": "GRA15: 7895856"
  },
  {
    "caption": "A. Top, WB of ULK1-complex components in wt and KO-OFD1 cells assessed in FM (-) or STV (2,4h). Bands at same exposure, noncontiguous on the same gel. Bottom, ACTIN-normalized protein levels are expressed as fold increase compared with wt cells, represented by the dashed line (mean ± SEM); n=5 independent experiments. FM=full medium, STV=HBSS starvation.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "B. Top, wild-type and KO-OFD1 cells were incubated with 50µg/ml CHX. Immunoblots were probed with indicated antibodies. Bottom, quantification of βTUBULIN and ACTIN-normalized protein levels versus untreated conditions (-), data are expressed as mean ± SEM; n=4 independent experiments. CHX=Cycloheximide, ns=not significative.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "C. Immunofluorescence of ULK1 and ATG13 puncta in wt and KO-OFD1 cells cultured in HBSS (90min). Green, ATG13 and ULK1; blue, Hoechst for nuclei. Scale bar=10μm. (Right) Graphs display quantification of puncta/cell, data are expressed as mean ± SEM; n=5 independent experiments, n≥200 cells/antibody.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "D. Western Blot of ULK1 complex components in KO-OFD1 cells transfected with empty vector (Empty) or 3xFLAG-OFD1 (OFD1). Histograms show quantification of band intensities normalized versus ACTIN expressed as mean ± SEM. n=5 independent experiments.",
    "ncbi_link": "FLAG: 
OFD1: 8481"
  },
  {
    "caption": "E. Western Blot of ULK1-complex components in KO-OFD1 cells transfected with 3xFLAG-OFD1 (OFD1) or empty vector (Empty) and treated (+) or not (-) with SAR405 (10μM, 6h). ACTIN is the loading control. On the right, ATG13 levels are expressed as fold increase compared with empty vector (mean ± SEM); n=3 independent experiments.",
    "ncbi_link": "FLAG: 
OFD1: 8481"
  },
  {
    "caption": "F. Representative confocal images of co-staining of 3xFLAG-OFD1 with ATG13 in KO-OFD1 cells incubated in HBSS, treated (+) or not (-) with Baf-A1(100nM, 90min). Green, ATG13; red, 3xFLAG-OFD1; blue, Hoechst for nuclei. Scale bar=10μm. (Right) ATG13 puncta/cell are quantified and expressed as mean ± SEM; n=3 independent experiments, n≥100 cells.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "A. Representative confocal images of 3xFLAG-OFD1 (OFD1) and 3xFLAG-OFD1∆LIR (OFD1∆LIR) co-staining with ATG13 in KO-OFD1 cells (HBSS,90min). Green, ATG13; red, FLAG; blue, Hoechst for nuclei. Scale bar=10μm. (Right) ATG13 puncta/cell are quantified and expressed as mean ± SEM; n=4 independent experiments, n≥100 cells.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "B. Western blot of ATG13 in KO-OFD1 cells transfected with 3xFLAG-OFD1 (OFD1) or 3xFLAG-OFD1∆LIR (OFD1∆LIR) or empty vector (Empty). (Right) ACTIN-normalized ATG13 protein levels are expressed as fold increase compared with empty vector (mean ± SEM); n=3 independent experiments.",
    "ncbi_link": "FLAG: 
OFD1: 8481"
  },
  {
    "caption": "D. Scanning confocal microscopy analysis of wt and KO-OFD1 cells incubated in HBSS (8h), treated (+) or not (-) with Baf-A1(50nM, 8h). Green, LAMP1; red, ATG13; blue, Hoechst for nuclei. Scale bar=6μm. Insets show higher magnification and single colour channels of the boxed area. (Bottom) Bar graphs show quantification of lysosomes containing ATG13 expressed as % of total amount of LAMP1/cell (mean ± SEM). n=30 WT cells, n=28 KO-OFD1 cells counted; three independent experiments.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "F. Western blot of FLAG in KO-OFD1 cells transfected with 3xFLAG-OFD1 (OFD1) or 3xFLAG-OFD1∆LIR (OFD1∆LIR) and treated or not (-) with Baf-A1 (100nM,2h). (Right) Quantification of GAPDH-normalized FLAG levels versus untreated (-) is expressed as mean ± SEM; n=3 independent experiments. Baf-A1=bafilomycin.",
    "ncbi_link": "FLAG: 
OFD1: 8481"
  },
  {
    "caption": "A. Representative blots of ATG13 (left) and VPS34 (right) phosphorylation levels in wt and KO-OFD1 cells transiently expressing GFP-ATG13 and FLAG-VPS34 in FM.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "B. Wild-type and KO-OFD1 cells were starved in HBSS with/without Baf-A1 (100nM, 2h) and chloroquine (CQ) (50μM, 2h) and total lysates were analyzed by immunoblotting using anti-OFD1, -LC3B (LC3B-I 18 kDa and LC3B-II 16 kDa) and -ACTIN antibodies. (Right) ACTIN-normalized LC3B-II levels are expressed as fold change versus untreated conditions (-) of wt cells. n=5 independent experiments.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "C. Representative images of LC3B and WIPI2 puncta in wt and KO-OFD1 cells (HBSS, 90min). Green, LC3B; red, WIPI2; blue, Hoechst, nuclei. Scale bar=10μm. (Right) Quantification of LC3B and WIPI2 puncta is shown. ≥100 cells analyzed/sample, n=5 independent experiments.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "D. Transmission electron microscopy (left) and quantification (right) of autophagic vacuoles (arrows) in wt and KO-OFD1 cells (HBSS, 90min).",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "E. Representative images of siOFD1 depleted and control (Ctrl) HeLa cells transiently expressing mRFP-eGFP-LC3B (HBSS, 90min). Insets show higher magnification of colocalization in selected areas. Scale bar=10μm. Bottom, tandem structure of the mRFP-GFP-LC3B construct and quantification of RFP+GFP+ and RFP+GFP- puncta in siOFD1-depleted cells and controls, cultured in full medium (FM) or kept in HBSS for 2h (STV) are depicted. n≥90 cells/sample analyzed, n=5 independent experiments.",
    "ncbi_link": "GFP: 
mRFP: 
LC3B: 81631
OFD1: 8481"
  },
  {
    "caption": "F. Representative images of WIPI2 staining in wt HK2 cells transiently expressing eGFP-OFD1 (HBSS,90min). Green, eGFP-OFD1, red, WIPI2; blue, Hoechst labels nuclei. On the right, quantification of WIPI2 puncta in eGFP-OFD1 transfected cells compared with non-transfected cells (Ctrl) is shown. Scale bar=10μm. n≥90 cells analyzed/sample, n=3 independent experiments.",
    "ncbi_link": "eGFP: 
OFD1: 8481"
  },
  {
    "caption": "G. Representative images of WIPI2 and OFD1 co-staining in KO-OFD1 cells transfected with empty vector (Empty), 3xFLAG-OFD1 (OFD1) or 3xFLAG-OFD1∆LIR (OFD1∆LIR) (HBSS,90min). Red, WIPI2; green, OFD1; blue, Hoechst labels nuclei. Scale bars: 10μm. On the right, quantification of WIPI2 puncta. ≥100 cells analyzed/sample, n=4 independent experiments.",
    "ncbi_link": "FLAG: 
OFD1: 8481"
  },
  {
    "caption": "A. Western blot of LC3B in kidney homogenates from leupeptin-treated (40mg/kg, 6h) fasted Ofd1fl/y;creKsp and control mice. (Right) LC3B-II protein levels normalized to Actin (loading control) are expressed as fold increase versus control mice, n=4 mice/group.",
    "ncbi_link": "Ksp: 12556
cre: 2777477
Ofd1: 237222"
  },
  {
    "caption": "B. Representative images of GFP-LC3 puncta (autophagosomes, green) in aquaporin2-positive (AQP2, red) renal distal tubules from P8 Ofd1fl/y;creKsp;GFP-LC3 and Ofd1fl/y;GFP-LC3 mice. Scale bar=10μm. Hoechst labels nuclei. Bar graphs on the left show quantitative analysis of GFP-LC3 puncta; n=4 mice/group for a total of 300 AQP2 positive nuclei/group analyzed.",
    "ncbi_link": "cre: 2777477
Ofd1: 237222"
  },
  {
    "caption": "C. Western blot of LC3B in kidney homogenates from leupeptin-treated (40mg/kg, 6h) fasted Ofd1-IND and control mice. (Right) LC3B-II protein levels relative to βTubulin (loading control) are expressed as fold increase compared with control mice, n=5 mutant/8 control mice .",
    "ncbi_link": "Ofd1: 237222"
  },
  {
    "caption": "D. Western blot of Atg13 in Ofd1fl/y;creKsp and control kidneys at pre-cystic (P8, left) and cystic (P22, right) stages. Gapdh was used as loading control. Atg13 protein levels are expressed as fold change compared with control mice; n=7 mutant/5 control mice at P8, n= 4mice/group at P22.",
    "ncbi_link": "Ksp: 12556
cre: 2777477
Ofd1: 237222"
  },
  {
    "caption": "E. Haematoxylin & eosin staining of kidney sections from Ofd1fl/y;Atg7+/+;creKsp and Ofd1fl/y;Atg7fl/fl;creKsp mice. (Right) Graph shows fold change of the cysts number observed in Ofd1fl/y;Atg7fl/fl;creKsp animals compared with Ofd1fl/y;Atg7+/+;creKsp; n=12 sections/animal were analyzed; n=6 mice/group. Scale bars=1mm.",
    "ncbi_link": "Atg7: 74244
Ksp: 12556
cre: 2777477
Ofd1: 237222"
  },
  {
    "caption": "F. Blood Urea Nitrogen was quantified on blood withdrawn from Ofd1fl/y;Atg7fl/fl;creKsp, Ofd1fl/y;Atg7+/+;creKsp and control mice at P45. n=8 mice per group.",
    "ncbi_link": "Atg7: 74244
Ksp: 12556
cre: 2777477
Ofd1: 237222"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target region of sgAkt1E17K in wild-type (WT) and base edited (BE) cells. Arrowheads highlight cytosines of the protospacer that show base editing 5 days after transduction of BE3-expressing NIH3T3 cells with Lenti-sgAkt1E17K. EditR (Kluesner et al., 2018) was used to calculate the frequency (%) of C-to-T conversion at C7 of the protospacer targeted by sgAkt1E17K in BE3-expressing NIH3T3 cells 5 days after transduction with the indicated sgRNA vectors.",
    "ncbi_link": "Akt1: 11651"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgAkt1E17K-Myc (n=12) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (58 days after injection vs 72 days after injection, P < 0.01 by Mantel-Cox test).",
    "ncbi_link": "Myc: 
Akt1: 11651"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target region of sgAkt1E17K in 3 independent tumors from WB1P-BE3 females injected with Lenti-sgAkt1E17K-Myc. Arrowheads highlight cytosines of the protospacer that show base editing. EditR was used to calculate the average frequency (%) of C-to-T conversion at C7 of the protospacer in tumors from WB1P-BE3 females injected with Lenti-sgNT-Myc or Lenti-sgAkt1E17K-Myc.",
    "ncbi_link": "Myc: 
Akt1: 11651"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target regions of sgPik3caE542K, sgPik3caE545K and sgPik3caE453K in wild-type (WT) and base edited (BE) cells. Arrowheads highlight cytosines of the protospacers that show base editing 5 days after transduction of BE3-expressing NIH3T3 cells with Lenti-sgPik3caE542K, Lenti-sgPik3caE545K and Lenti-sgPik3caE453K.",
    "ncbi_link": "Pik3ca: 18706"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgPik3caE542K-Myc (n=10), Lenti-sgPik3caE545K-Myc (n=10) and Lenti-sgPik3caE453K-Myc (n=10) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (respectively 47, 44 and 49 days after injection vs 72 days after injection, P < 0.0001 by Mantel-Cox test).",
    "ncbi_link": "Myc: 
Pik3ca: 18706"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target region of sgPik3caE542K, sgPik3caE545K and sgPik3caE453K in 3 independent tumors from WB1P-BE3 females injected with the corresponding Lenti-sgPik3ca-Myc vectors. Arrowheads highlight cytosines of the protospacer that show base editing. EditR was used to calculate the average frequency (%) of C-to-T conversion at the indicated target cytosines of the protospacers in tumors from WB1P-BE3 females injected with Lenti-sgNT-Myc or Lenti-sgPik3caE542K-Myc, Lenti-sgPik3caE545K-Myc and Lenti-sgPik3caE453K-Myc.",
    "ncbi_link": "Myc: 
Pik3ca: 18706"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target region of sgPtenQ245* in wild-type (WT) and base edited (BE) cells. Arrowheads highlight cytosines of the protospacer that show base editing 5 days after transduction of BE3-expressing NIH3T3 cells with Lenti-sgPtenQ245*. EditR was used to calculate the frequency (%) of C-to-T conversion at C4 of the protospacer targeted by sgPtenQ245* in BE3-expressing NIH3T3 cells 5 days after transduction with the indicated sgRNA vectors.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WB1P-BE3 females injected with Lenti-sgPtenQ245*-Myc (n=11) showed a reduced mammary tumor-specific survival compared to WB1P-BE3 female mice injected with Lenti-sgNT-Myc (n=11) vectors (37 days after injection vs 72 days after injection, P < 0.0001 by Mantel-Cox test).",
    "ncbi_link": "Myc: 
Pten: 19211"
  },
  {
    "caption": "BE Analyzer (Hwang et al., 2018) was used to assess from next-generation sequencing data the fraction of wild-type Pten alleles, base edited alleles or alleles with insertions/deletions (indels) in tumors from WB1P-BE3 animals injected with Lenti-sgNT-Myc or Lenti-sgPtenQ245*-Myc. TIDE analysis showing the spectrum of indels of the targeted Pten alleles in two independent representative tumors from WB1P-BE3 mice injected with Lenti-sgPtenQ245*-Myc. For the two tumors shown in (F), Sanger-sequencing chromatograms showing the target region of sgPtenQ245* (PCR products were subcloned for clarity). Arrowheads highlight cytosines of the protospacer that show base editing. In the lower example the gene was inactivated by indels at both alleles, while in the upper one by Q245* base editing in one allele and a deletion at the second copy of the gene.",
    "ncbi_link": "Myc: 
Pten: 19211"
  },
  {
    "caption": "Sanger-sequencing chromatograms showing the target region of sgTrp53Q97* in wild-type (WT) and base edited (BE) cells. Arrowheads highlight cytosines of the protospacer that show base editing 5 days after transduction of BE3-expressing NIH3T3 cells with Lenti-sgTrp53Q97 EditR was used to calculate the frequency (%) of C-to-T conversion at C8 of the protospacer targeted by sgTrp53Q97* in BE3-expressing NIH3T3 cells 5 days after transduction with the indicated sgRNA vectors.",
    "ncbi_link": "Trp53: 22059"
  },
  {
    "caption": "Kaplan-Meier curves showing mammary tumor-specific survival for the different models. WapCre;Brca1F/F;Trp53F/+;Col1a1invCAG-BE3/+ females injected with Lenti-sgPik3caE545K/sgTrp53Q97*-Myc (n=6) showed a reduced mammary tumor-specific survival compared to animals injected with Lenti-sgTrp53Q97*-Myc (n=5) vectors (76 days after injection vs 101 days after injection, P < 0.05 by Mantel-Cox test). Females injected with Lenti-sgNT-Myc (n=11) did not develop any palpable tumors during the 150 days observation period.",
    "ncbi_link": "Myc: 
Brca1: 12189
Col1a1: 12842
Cre: 2777477
Pik3ca: 18706
Trp53: 22059
Wap: 22373"
  },
  {
    "caption": "BE Analyzer was used to assess from next-generation sequencing data the fraction of wild-type Trp53 alleles, base edited alleles or alleles with indels in tumors from WapCre;Brca1F/F;Trp53F/+;Col1a1invCAG-BE3/+ animals injected with Lenti-sgTrp53Q97*-Myc. Tumors from WB1P-BE3 animals injected with Lenti-sgNT-Myc mice were used as control. TIDE analysis showing the spectrum of indels of the targeted Trp53 alleles in two independent representative tumors from WapCre;Brca1F/F;Trp53F/+;Col1a1invCAG-BE3/+ mice injected with Lenti-sgTrp53Q97*-Myc. For the two tumors shown in (F), Sanger-sequencing chromatograms showing the target region of sgTrp53Q97*. Arrowheads highlight cytosines of the protospacer that show base editing. In the lower example the gene was inactivated by a deletion, while in the upper one by Q97* base editing. Of note, the allele with the indel also displays base editing at C6 of the protospacer.",
    "ncbi_link": "Myc: 
Brca1: 12189
Col1a1: 12842
Cre: 2777477
Trp53: 22059
Wap: 22373"
  },
  {
    "caption": "F. Cells from all FDo were stably transduced, as indicated. Intracellular α-galactosidase A (α-gal A) specific activities were determined. G, H. Secreted α-gal A activity was measured from FDo-derived TRaMs in activated (G), and quiescent/resting (H) states. I",
    "ncbi_link": "α-gal A: 2717"
  },
  {
    "caption": "a, Immunoblot analysis of Atg5 and LC3. Brain homogenates were prepared from six-week-old control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre (Atg5flox/flox) mice. Immunoblot analysis was performed using antibodies against Atg5 and LC3. GSK-3β was used as a loading control. The positions of the Atg12-Atg5 conjugate, LC3-I and LC3-II (LC3-PE conjugate) are indicated. Atg5 monomer was not detected in either lane (data not shown).",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "b, A representative male control (Atg5flox/+; nestin-Cre) and an Atg5flox/flox; nestin-Cre (Atg5flox/flox) littermate at three weeks of age.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "c, Left, paw placement records of eight-week-old mice. Right, stride lengths corrected for paw base widths (stride/width ratio) of Atg5flox/flox; nestin-Cre and control (Atg5flox/+; nestin-Cre) littermate mice. Values represent means ± s.d. of four mice. Asterisk, P 0.01 (Students t-test).",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "d, Abnormal limb-clasping of an Atg5flox/flox; nestin-Cre mouse compared with a control mouse (Atg5flox/+; nestin-Cre) when suspended by its tail.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "e, Rotarod testing of Atg5flox/+; nestin-Cre (open symbols) and Atg5flox/flox; nestin-Cre (closed symbols) mice. One male and one female mouse were analysed for each genotype. The time until drop from the rod (rotating at 20 r.p.m.) is shown.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "a, HE-stained sections of the cerebral cortex, the gracile nucleus and cerebellum from control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre (Atg5flox/flox) mice at three months of age. Purkinje cells are indicated with arrowheads. Arrows indicate eosinophilic spheroids, which represent axon swelling. Scale bar, 10 µm.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "b, Immunohistochemistry using an anti-calbindin antibody on cerebellum sections from control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre mice at six weeks of age. Scale bar, 25 µm.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "c, Loss of Purkinje cells in Atg5flox/flox; nestin-Cre mice. Purkinje cells were counted in comparable areas for each mouse, and three fields were counted in each area for each mouse. Data are normalized against values from control mice (Atg5flox/+; nestin-Cre). Values represent mean ± s.d. of three mice. Asterisk, P 0.01 (t-test).",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "d, Apoptotic death of granular cells. Cerebellum sections from control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre mice at six weeks of age were subjected to TUNEL staining. Nuclei were stained with Hoechst 33258. Scale bar, 500 µm.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "a, Immunohistochemistry of brain sections from control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre (Atg5flox/flox) mice at six weeks of age, stained with an anti-ubiquitin antibody (1B3). Scale bar, 10 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, Ubiquitin-positive inclusions in neurons. Sections of medulla from Atg5flox/flox; nestin-Cre mice at six weeks of age were stained with an antibody against NeuN (a neuron-specific nuclear protein) and ubiquitin. Nuclei were stained with Hoechst 33258. Scale bar, 10 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, Immunoelectron microscopy of ubiquitin-positive inclusion bodies. DRG neurons isolated from Atg5-/- neonates were analysed by immunoelectron microscopy using an anti-ubiquitin antibody. Scale bars, 500 nm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "a, Immunohistochemistry of DRG neurons from Atg5+/+ and Atg5-/- mice at different developmental stages (embryonic day (E)13.5, E15.5 or postnatal day (P)0), stained with an antibody directed against ubiquitin. Scale bar, 25 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, Accumulation of Triton-X-100-solublepolyubiquitinated proteins in the brains of Atg5flox/flox; nestin-Cre mice. Brain homogenate prepared at the indicated times from control (Atg5flox/+; nestin-Cre) and Atg5flox/flox; nestin-Cre (Atg5flox/flox) mice were separated into Triton-X-100-soluble (S) and -insoluble (P) fractions and analysed by immunoblotting using anti-ubiquitin antibodies. Arrowhead indicates the stacking gel.",
    "ncbi_link": "Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "c, Immunohistochemistry of liver sections from control (Atg5flox/+; CAG-Cre) and Atg5flox/flox; CAG-Cre (Atg5flox/flox) mice at four months of age, using an anti-ubiquitin antibody. Scale bar, 25 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, Immunohistochemistry of liver sections from six-week-old Atg5flox/flox; Mx1-Cre mice at the indicated time points after pIpC injection, using anti-ubiquitin antibodies. Arrowheads indicate ubiquitin-positive inclusion bodies. Scale bar, 25 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(D) HEK293T cells transfected with optoYAP were subjected to three cycles of activation protocol and recovery in the dark. (Top) The ratio of mCherry-optoYAP signal in the nucleus to the cytoplasmic mCherry-optoYAP signal (n=8 cells from 2 independent experiments). (Bottom) Representative images of the mCherry-optoYAP signal from the same HEK293T cells at each cycle. Scale bars, 10 μm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "(B) Example images of embryos expressing optofYap (mCherry-tagged) in the EVL and deep cells kept in the dark or subjected to the activation protocol at 6 hpf. Scale bars, 10 μm. (B') Fold-change in nuclear localisation of mCherry-optofYap (n=20 cells from 3 independent experiments).",
    "ncbi_link": "mCherry: 
Yap: 561411"
  },
  {
    "caption": "(A) Left panel, representative images of organotypic cultures of E18 mouse cortical neurons transfected with GFP-RFP-LC3B and transduced with lentivirus expressing either control shRNA or shRNA targeting C9orf72 mRNA and treated or not with Torin. Right panel, quantification of LC3B puncta.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(B) Upper panel, immunoblot analysis of endogenous LC3B (Map1lc3b), C9orf72 and control Actin of E18 mouse cortical neurons transduced with lentivirus expressing either control shRNA or shRNA targeting C9orf72 mRNA and treated or not with Torin. Lower panel, real time RT-qPCR quantification of endogenous C9orf72 mRNA expression relative to Rplp0 mRNA.",
    "ncbi_link": "Rplp0: 
C9orf72: 73205"
  },
  {
    "caption": "(C) Left panel, representative images of immunofluorescence labeling of endogenous P62 (Sqstm1) on organotypic cultures of E18 mouse cortical neurons transduced with lentiviral particles expressing either control shRNA or shRNA targeting C9orf72. Right panel, quantification of P62 aggregates.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(D) Left panel, representative images of immunofluorescence labeling of transfected constructs (Green) and endogenous P62 (Sqstm1, red) on GT1-7 neuronal cells transfected with siRNA targeting C9orf72 and plasmids expressing control GFP, HA tagged wild type or mutant RAB39b (CA, Q68L or CN, S22N), RAB8a or RAB7. Right panel, quantification of P62 aggregates. Scale bars, 10 µm. Nuclei were counterstained with DAPI. Error bars indicate s.e.m. Student T-test, * indicates p<0.05, *** indicates p<0.001. n=3.",
    "ncbi_link": "C9orf72: 73205
RAB39b: 67790
RAB7: 19349
RAB8a: 17274"
  },
  {
    "caption": "(D) Left panel, representative images of immunofluorescence labeling of transfected constructs (Green) and endogenous P62 (Sqstm1, red) on GT1-7 neuronal cells transfected with siRNA targeting the 3'UTR of Smcr8 mRNA and plasmids expressing control GFP, HA tagged wild type or mutant SMCR8 (TA, S402A and T796A; TD, S402D and T796D; UD, S400D, S492D, S562D and T666D). Right panel, quantification of P62 aggregates.",
    "ncbi_link": "Smcr8: 237782"
  },
  {
    "caption": "(E) Left panel, representative images of immunofluorescence labeling of transfected constructs (Green) and endogenous P62 (Sqstm1, red) on GT1-7 neuronal cells transfected with siRNA targeting Tbk1 and plasmids expressing control GFP, HA tagged wild type or mutant SMCR8 or RAB39b. Right panel, quantification of P62 aggregates. Scale bars, 10 µm. Nuclei were counterstained with DAPI. Error bars indicate s.e.m. Student T-test, * indicates p<0.05, *** indicates p<0.001. n=3.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "(A) Immunoblot analysis of endogenous Tdp-43, C9orf72 and control Gapdh of E18 mouse cortical neurons transduced with lentivirus expressing either control shRNA or shRNA targeting C9orf72 mRNA.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(B) Left panel, representative images of immunofluorescence labeling of endogenous phosphorylated Ser409/410-Tdp-43 on primary cultures of E18 mouse cortical neurons transduced with lentiviral particles expressing either control shRNA or shRNA targeting C9orf72. Right panel, quantification of cytoplasmic Tdp-43 aggregates.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(C) Left panel, representative images of immunofluorescence labeling of D169G mutant GFP-tagged TDP-43 on primary cultures of E18 mouse cortical neurons transfected with either HA-tagged control or HA-C9ORF72 plasmid. Right panel, quantification of cells with cytoplasmic aggregates of TDP-43. Scale bars, 10 µm. Nuclei were counterstained with DAPI. Error bars indicate s.e.m. Student T-test, *** indicates p<0.001. n=3.",
    "ncbi_link": "C9ORF72: 203228"
  },
  {
    "caption": "(A) Left panel, representative images of organotypic cultures of E18 mouse cortical neurons co-transfected with HA-tagged ATXN2 with control (Q22x) or intermediate (Q30x) polyQ size and transduced with lentivirus expressing either control shRNA or shRNA targeting C9orf72 mRNA. Right panel, quantification of ATXN2 aggregates. Scale bars, 10 µm. Nuclei were counterstained with DAPI.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(B) Cell viability (tetrazolium assay) of GT1-7 neuronal cells co-transfected with HA-tagged ATXN2 with control (Q22x) or intermediate (Q30x) polyQ size and control siRNA or siRNA targeting C9orf72 mRNA. Error bars indicate s.e.m. Student T-test, *** indicates p<0.001. n=3.",
    "ncbi_link": "C9orf72: 73205"
  },
  {
    "caption": "(C) Tracing of the swimming trajectories of 48 hours post-fertilization zebrafish larvae following light touch. (D-F) Quantification of the touch-evoked swimming distance (D), average velocity (E), and maximum velocity attained (F) shows significant functional impairment of the zebrafish injected with HA-tagged ATXN2 with intermediate length of polyQ (Q30x) and antisense morpholino oligonucleotides (AMOs) against C9orf72 compared to control HA-tagged ATXN2 (Q22x) or to the sole injection of AMO against C9orf72.",
    "ncbi_link": "ATXN2: 6311
C9orf72: 402895"
  },
  {
    "caption": "(G) Representative images of motor neurons visualized with anti-Sv2 immunohistochemistry show severe axonopathy in fish injected with both ATXN2 Q30x and AMO against C9orf72 compared to zebrafish injected with control ATXN2 Q22x or with AMO against C9orf72 alone. (H) Quantification of the motor neuron axonal length demonstrates a significant decrease of axonal length in 48 hours post-fertilization zebrafish larvae injected with both ATXN2 Q30x and AMO against C9orf72 compared to controls. Error bars indicate s.e.m. One-way ANOVA, ** indicates p<0.01. n=3.",
    "ncbi_link": "ATXN2: 6311
C9orf72: 402895"
  },
  {
    "caption": "(C) Chromatin was extracted from BJ  cells treated with vehicle or  abemaciclib (1 μM for 8 times 24 hours) or nutlin-3a (10 μM for 8 times 24 hours) or doxorubicin (250 nM for 24 hours) and ChIP  assays using an antibody against  p53 were performed. qRT-PCR was performed using primers amplifying promoter regions of CDKN1A, GADD45A and MDM2 genes containing  p53 binding sites. Values indicate fold enrichment relative to the vehicle group (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CDKN1A: 1026
GADD45A: 1647
MDM2: 4193"
  },
  {
    "caption": "(I) RNA was isolated from vehicle or abemaciclib (1 μM) treated scramble/shp53 BJ cells and mRNA for the indicated genes quantified by qRT-PCR relative to  tubulin (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "p53: 7157
tubulin: 7846"
  },
  {
    "caption": "p16-3MR  mice were treated with vehicle (PBS, 7 consecutive days),  doxorubicin (5 mg/kg, 3 consecutive days) or abemaciclib (50 mg/kg, 7 consecutive days). n=6  mice/group. 14 dpt, bioluminescence was visualized and quantified by the IVIS spectrum in vivo imaging system, as shown by representative bioluminescence images (A) and quantification (B). Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant.",
    "ncbi_link": "p16: 12578"
  },
  {
    "caption": "p16-3MR  mice were treated with vehicle (PBS, 7 consecutive days), doxorubicin (5 mg/kg, 3 consecutive days) or abemaciclib (50 mg/kg, 7 consecutive days). n=6 mice/group. RNA isolated from  kidneys and mRNA encoding p16 quantified by qRT-PCR (C). SA-β-gal activities in vehicle-, doxorubicin- or  abemaciclib-treated mouse kidney sections at 15 dpt quantified (E). Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant.",
    "ncbi_link": "p16: 12578"
  },
  {
    "caption": "(G) RNA was isolated from abemaciclib ±  pifithrin-α  treated  kidneys  and mRNA encoding p16  and p21 genes was quantified by qRT-PCR and normalized on tubulin (n=5 mice/group). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant.",
    "ncbi_link": "p16: 12578
p21: 67676
tubulin: 22142"
  },
  {
    "caption": "(B) BJ cells transduced with a NF-κB reporter were treated with vehicle, doxorubicin, paclitaxel (50 nM for 24 hours),  palbociclib  (1 μM for 8 times 24 hours) or abemaciclib and luciferase activity measured 8 dpt.  TNFα treatment was used as positive control (n=3 independent experiments). Data information: Data are means ±SD. One-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.= Not significant.",
    "ncbi_link": "NF-κB: 4791///4790"
  },
  {
    "caption": "p16-3MR mice were treated with vehicle (PBS, 7 consecutive days), doxorubicin (5 mg/kg, 3 consecutive days) or  abemaciclib (50 mg/kg, 7 consecutive days). RNA isolated from kidneys and mRNA encoding indicated NF-κB  associated genes (J) quantified by qRT-PCR. n=6 mice/group. Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001, N.S.= Not significant.",
    "ncbi_link": "p16: 12578"
  },
  {
    "caption": "p16-3MR  mice were treated with vehicle (PBS, 7 consecutive days), doxorubicin (5 mg/kg, 3 consecutive days) or abemaciclib (50 mg/kg, 7 consecutive days). From a subset of the mice, RFP+ cells were sorted from the  renal cortex using  FACS and mRNA encoding indicated NF-κB associated pro-inflammatory genes quantified by qRT-PCR. The values of fold change over vehicle were plotted in the heatmap. n=4 mice/group (K).",
    "ncbi_link": "p16: 12578"
  },
  {
    "caption": "(B)  Human BJ fibroblasts,  hTERT-RPE1 epithelial cells  and lung mesenchymal stem cells were treated with vehicle (DMSO for 8 times 24 hours) or doxorubicin (250 nM for 24 hours) or paclitaxel (50 nM for 24 hours) or palbociclib (1 μM for 8 times 24 hours) or abemaciclib  (1 μM for 8 times 24 hours). At 8 dpt, RNA was isolated and mRNA for the indicated  p53-associated SASP genes quantified by qRT-PCR relative to  tubulin (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "p53: 7157
tubulin: 7846"
  },
  {
    "caption": "(D and E) RNA was isolated from vehicle, abemaciclib (1 μM) (D) or palbociclib (1 μM) (E) treated scramble/shp53 BJ cells and quantified by qRT-PCR for  IGFBP3 or LIF genes (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "IGFBP3: 3486
LIF: 3976
p53: 7157"
  },
  {
    "caption": "(F) RNA isolated from  kidneys treated with  doxorubicin or abemaciclib and mRNA encoding indicated  p53-associated SASP genes quantified by qRT-PCR (n=6 mice/group). (G) RNA was isolated from kidneys of  p16-3MR mice treated with abemaciclib (50 mg/kg, 7 consecutive days) ± pifithrin-α (2 mg/kg, 7 consecutive days), and mRNA encoding  p53 associated SASP genes was quantified by qRT-PCR and normalized on  tubulin (n=5  mice/group). ( Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "p16: 12578
p53: 22059
tubulin: 22142"
  },
  {
    "caption": "(I) RNA was isolated from vehicle or nutlin-3a (1 μM for 8 times 24 hours) treated BJ  cells at 8 dpt and quantified by qRT-PCR for p53 target cell cycle genes, SASP genes (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(J)  Mouse dermal fibroblasts  (MDF) or MDF-p53-/- fibroblasts were transfected with empty vector (EV) or p53-overexpressing vector (p53OE), then the cells were treated with vehicle (water) or doxorubicin (250 nM for 24 hours) and qRT-PCR  was performed for Igfbp3  and Lif  genes (n=3 independent experiments). Data information: Data are means ±SD. Two-way ANOVA *p<0.05, **p<0.01, ***p<0.001. EV, empty vector",
    "ncbi_link": "Igfbp3: 16009
Lif: 16878
p53: 22059"
  },
  {
    "caption": "(H and I) 2*105 cells of vehicle-treated (water for 8 times 24 hours) mouse dermal fibroblasts  (MDF) were injected into the  left flank  of the p16-3MR  mice. Doxorubicin-induced (250 nM for 24 hours) (H) or abemaciclib-induced (4 μM for 8 times 24 hours) (I) MDFs were injected into the  right  flank  of the same animal. 7 dpt, the above-mentioned mice  were injected with coelenterazine and bioluminescence from the p16-3MR  mouse was visualized/quantified by the IVIS spectrum in vivo imaging system and quantified. Lower panel, scheme of experimental design (n=4 mice/group). Data information: Data are means ±SD. Paired student t-test *p<0.05, **p<0.01, ***p<0.001, N.S.=not significant.",
    "ncbi_link": "p16: 12578"
  },
  {
    "caption": "A ATX gene expression from publicly available datasets in NASH patients (n=9) compared to healthy controls (n=7) (*P < 0.05); cirrhosis patients (n=40) compared to healthy controls (n=19) (***P < 0.001). Bars represent the mean ± SEM, statistical analysis was performed by two-tailed student's t-test. *P < 0.05, ***P < 0.001 denotes significance versus respective healthy controls.",
    "ncbi_link": "ATX: 5168"
  },
  {
    "caption": "B Relative ATX gene expression in the MCD-diet-fed (n=9) compared to control mice  (n=9) (***P < 0.001); CCl4  (n=8) compared to control mice  (n=5) (*P < 0.05). Bars represent the mean ± SEM, statistical analysis was performed by two-tailed student's t-test. *P < 0.05, ***P < 0.001 denotes significance versus respective healthy controls.",
    "ncbi_link": "ATX: 18606"
  },
  {
    "caption": "C Relative gene expression (normalized with GAPDH) for CCL2   and iNOS  in control (M0) and LPS- and IFNγ-induced M1 RAW 264.7 macrophages  treated with medium alone, PF8380  (1μM) or Cpd17  (1μM). Bars represent the mean + SEM, n=4. Statistical analysis was performed by one-way analysis of variance (ANOVA) with Bonferroni post-hoc test. ####P < 0.0001 denotes significance versus M0 (non-stimulated macrophages) and *P < 0.05, **P < 0.01 denotes significance versus vehicle (LPS- and IFNγ-induced  M1 macrophages); ns=non-significant.",
    "ncbi_link": "CCL2: 20296
GAPDH: 14433
iNOS: 106736473"
  },
  {
    "caption": "D Relative gene expression (normalized with 18s RNA) for CCL2  and iNOS  in control (M0) and LPS-induced PMA-differentiated human THP1 macrophages  treated with medium alone, PF8380  (1μM) or Cpd17  (1μM). Bars represent the mean + SEM, n=4. Statistical analysis was performed by one-way analysis of variance (ANOVA) with Bonferroni post-hoc test. ##P < 0.01, ###P < 0.001 denotes significance versus M0 (non-stimulated macrophages) and **P < 0.01, ***P < 0.001 denotes significance versus vehicle (LPS- and IFNγ-induced M1 macrophages); ns=non-significant.",
    "ncbi_link": "18s RNA: 
CCL2: 6347
iNOS: 111365141"
  },
  {
    "caption": "B Relative Collagen I, α-SMA and PDGFβR gene expression (normalized with GAPDH) in control and TGFβ-activated LX2  cells with or without PF8380  (1μM) or Cpd17  (1μM). Bars represent the mean + SEM, n=3. Statistical analysis was performed by two-tailed student's t-test. #P < 0.05, ###P < 0.001 denotes significance versus control (non-TGFβ  cells) and **P < 0.01 denotes significance versus vehicle (TGFβ-activated cells); ns=non-significant.",
    "ncbi_link": "α-SMA: 59
Collagen I: 1277///1278
GAPDH: 2597
PDGFβR: 5159"
  },
  {
    "caption": "(A) Tamoxifen schedule: pulse of the pregnant dam at E9.5, harvest at E10.5. Representative fluorescent immune-staining of E10.5 Sox7iECKO mutants and sibling control embryos. The endothelium is delineated by endomucin (EMCN) (blue) and endothelial cells by ETS-related gene (ERG) (red), SOX7 positive cells are shown in white. (Top right graph) The percentage of SOX7 positive endothelial cells in different vascular beds, quantified from 10 sequential transverse sections in 2 control and 3 Sox7iECKO mutants. (Bottom right panel) Graph indicating the levels of Sox7 transcript in sibling controls and Sox7iECKO mutants. Mean ± SEM; scored sibling control, n=9; Sox7iECKO mutants, n=7; Mann-Whitney U-test. P<0.0005 (***).",
    "ncbi_link": "Sox7: 20680"
  },
  {
    "caption": "(C) Brightfield images and whole-mount immunostaining of Sox7iECKO mutant and sibling control skin at E13.5, after Cre induction at E9.5 and E10.5. Dermal lymphatic structures are marked by Neuropilin 2 (NRP2) (membranous white), lymphatic endothelial cells by Prospero-related homeobox 1 (PROX1) (red), and blood vessels by EMCN (green). Dash line represents the midline of the embryo. Scored sibling controls, n=7; Sox7iECKO mutants, n=7",
    "ncbi_link": "Cre: 2777477
Sox7: 20680"
  },
  {
    "caption": "(D-H) Quantification of (D) Distance of the lymphatic vessel front from the midline (μm) (E) lymphatic branch points/area (F) lymphatic vessel width (μm) (G) PROX1+ nuclei/area and (H) PROX1+ nuclei/lymphatic vessels across the whole skin. Total area = 4200 x 1500 μm on both sides of the midline, in sibling controls (n=3) and Sox7iECKO mutants (n=5-6). (F,H) Average of width and PROX1+ nuclei was obtained from 7 random representative leading lymphatic vessels, of fixed length at 200 μm, from both sides of the midline in each skin. (I,J) Quantification of (I) PROX1+ nuclei in each LEC cluster with each colour dot representing a different embryo and (J) disconnected lymphatic endothelial cell (LEC) clusters (<100 μm) and vessel branches (>100μm)/area. Total area quantified = 4200 x 2200 μm on both side of midline in sibling controls (n=3) and Sox7iECKO mutants (n=5). PROX1+ nuclei were quantified from n=29 and n=122 LEC clusters, respectively.",
    "ncbi_link": "Sox7: 20680"
  },
  {
    "caption": "(C) Arterial endothelial cells express Vegfc transcripts. Transverse section of a E10.5 wild-type embryo stained by single molecule FISH (smFISH) for Gapdh (green) and Vegfc (magenta) and immuno-stained for PECAM (white). The first panel shows a merged version of the pseudo colour signals for the 3 markers. Inset 1 shows the expression of Vegfc in endothelial cell of the dorsal aorta (black and white, pink arrows). Inset 2 shows the high expression levels of mesenchymal Vegfc expressed in the dorso-lateral aspects of the cardinal vein.",
    "ncbi_link": "Gapdh: 14433
Vegfc: 22341"
  },
  {
    "caption": "(E-F) qPCR on human arterial endothelial cells (HUAECs) transfected with SiSOX7 or SiCTRL for (E) 30 h and (F) 17 h. (G) qPCR on human venous endothelial cells (HUVECS) transfected with SiSOX7 or SiCTRL for 17 h. D",
    "ncbi_link": "SOX7: 83595"
  },
  {
    "caption": "(A-D) SOX7 transcriptionally activates Notch effector, HEY1, to repress Vegfc. (A) qPCR on FAC-sorted PECAM+CD45-endothelial cells of Sox7iECKO mutants and sibling controls at E14.5 after Cre induction with tamoxifen at E11.5 and E12.5. Expression is normalised to the endothelial marker Pecam and Cdh5. Scored sibling controls, n=9; Sox7iECKO mutants, n=8. (B-C) qPCR on (B) human arterial endothelial cells (HUAECs) and (C) human venous endothelial cells (HUVECs) transfected with SiSOX7 or SiCTRL for 17 h. In addition to HEY1, DLL4 levels were also downregulated in the human cell line experiments. Expression is relative to HPRT and GAPDH. Data from one siRNA experiment performed in triplicates. (D) HEY1 represses human VEGFC promoter activity. HeLa cells were co-transfected with human or mouse VEGFC-luc and either EV (empty vector) or HEY1 expression constructs as indicated. VEGFC luciferase activity was measured and normalised to Renillla luciferase activity, which was then made relative to the promoter-less vector, pGL3-basic, which was set to 1. Biological replicates, n=3 independent repeats of the same experiment. Mean ± SEM; t-test. P<0.05 (*); P<0.005 (**); P<0.0005 (***).",
    "ncbi_link": "HEY1: 
luc: 
Cdh5: 12562
Cre: 2777477
DLL4: 54567
GAPDH: 2597
HEY1: 15213
HEY1: 23462
HPRT: 3251
Pecam: 18613
SOX7: 20680
Sox7: 20680
SOX7: 83595
Vegfc: 22341
VEGFC: 7424
VEGFC: 22341"
  },
  {
    "caption": "SOX7 physically interacts with transcription repressor, HEY1. (G) Co-immnuno-precipitation analysis of SOX7 and HEY1. HEK293 cells were transfected with indicated plasmids and harvested 24 h after transfection, immunoprecipitated by anti-GFP or Ig control before immunoblot analysis to determine the presence of bait/prey (top) and the input (bottom). N=2.",
    "ncbi_link": "HEY1: 23462
SOX7: 83595"
  },
  {
    "caption": "(A) SOX7 represses human VEGFC promoter activity. HeLa cells were co-transfected with human or mouse VEGFC-luc, EV (empty vector), or SOX7 expression constructs as indicated. VEGFC luciferase activity was measured and normalised to Renillla luciferase activity, which was then made relative to the promoter-less vector, pGL3-basic, which was set to 1. Biological replicates, n=3. Mean ± SEM; t-test. P<0.05 (*).",
    "ncbi_link": "luc: 
SOX7: 
SOX7: 83595
VEGFC: 7424
VEGFC: 22341"
  },
  {
    "caption": "(G) Quantitation of Vegfc transcript using single molecule FISH in vivo. (colored panel) Representative low magnification images of the trunk transverse sections of E10.5 sibling controls and Sox7iECKO mutants showing the similar relative position of the DA and the CV across genotypes. Sections were stained by single molecule FISH (smFISH) for Gapdh (green) and Vegfc (magenta) and immuno-stained for PECAM (white). Individual molecules of Vegfc transcript (pink arrows) are detectable within the cytoplasm of PECAM positive cells of the dorsal aorta (Middle panel). (Left graph) Quantitation of Vegfc transcript level in the PECAM positive endothelial cells of the dorsal aorta, in sibling controls and Sox7iECKO mutants at E10.5. The mean grey scale intensity of the Vegfc probes in control was 5845. ­­­­­­­­­The mean grey scale intensity of the Vegfc probes in Sox7iECKO was 8956. Mean probe intensity was significantly higher in Sox7iECKO compared to the control (P<2e-16). (Right graph) No differences were observed for the average probe area, meaning that distribution of the probes across the dorsal aorta remained unchanged between control and Sox7iECKO. Scored sibling controls, n=5; Sox7iECKO mutants, n=7. Mean ± SEM; t-test. P<0.0005 (***), Graph: box, interquartile range, central band, median, whiskers, indicate maximum and minimum. Scale bars; low magnification 150 μm, high magnification, 30 μm",
    "ncbi_link": "Gapdh: 14433
Sox7: 20680
Vegfc: 22341"
  },
  {
    "caption": "(A) At 2 days post Cre induction, E11.5 Sox7iECKO mutants showed ectopic expression of PROX1+ (red) in medial ventral regions of the cardinal veins (CVs), close to dorsal aorta (DA) (yellow arrowheads).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(D) Whole-mount immunostaining of control and Sox7iECKO embryonic skin at E12.5 after Cre induction at E9.5, E10.5. Dermal lymphatic structures are stained with NRP2 (membranous white), lymphatic endothelial cells, PROX1 (red), and blood vessels, both EMCN (green) and SOX7 (white nuclei). Arrowheads indicate EMCNlow/-PROX1+NRP2+/low individual LECs on blood vessels (type I), and arrow shows EMCN+PROX1+ NRP2low/- LEC within the vessel wall (type II). (E) Graph shows the total events of PROX1+ single LECs or LEC clusters cells associated with EMCN+ blood vessel plexus within each embryo. PROX1+ cells were quantified from n=4 controls and n=5 Sox7iECKO mutants.",
    "ncbi_link": "Cre: 2777477
Sox7: 20680"
  },
  {
    "caption": "(a-c) HeLa cells transfected with ARL8B or KIF2 siRNA, or with ARL8B overexpression construct (non-targeting siRNA and empty pcDNA vector used as transfection controls), were either left untreated, serum/amino-acid starved for 5 h, or starved and then recovered in amino-acid- and FBS-containing medium for 30 min. Cells were immunostained using LAMP1 antibody (a) and the percentage of cells with predominantly peripheral localization of LAMP1-positive vesicles was quantified (b) or subjected to immunoblotting (c) using antibodies as shown. Quantification of phospho-S6K levels relative to the total S6K is shown in (c). Values are means ± s.e.m. of three independent experiments carried out in triplicate. All comparisons are with the control within each treatment condition, *P0.05, **P0.01, ***P0.005 Student's t-test; n.s. not significant. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "ARL8B: 55207
KIF2: 11004///84643///3796"
  },
  {
    "caption": "(e) Changes in lysosomal localization have no effect on pHi. ARL8B and KIF2 were overexpressed or knocked down in HeLa cells followed by pHi measurement.",
    "ncbi_link": "ARL8B: 55207
KIF2: 11004///84643///3796"
  },
  {
    "caption": "(c) ARL8B knockdown increases autophagosomal synthesis. siRNA-transfected HeLa cells were incubated for 48 h, then left untreated or incubated with bafilomycin A1. LC3-II levels versus actin were quantified (bottom graphs). Asterisk: nonspecific band.",
    "ncbi_link": "ARL8B: 55207"
  },
  {
    "caption": "(d) ARL8B overexpression inhibits autophagosome synthesis and degradation. HeLa cells overexpressing ARL8B or empty vector were analysed as in (c).",
    "ncbi_link": "ARL8B: 55207"
  },
  {
    "caption": "(e) HeLa cells were co-transfected with either ARL8B overexpression construct or siRNA (non-targeting siRNA and empty peGFP vector were transfection controls) together with mCherry-LC3 for 48 h. After fixation, cells were stained for endogenous LAMP1 and DNA (DAPI). Representative maximum-intensity projections of serial confocal optical sections are shown. Co-localization panels show overlapping mCherry-LC3 and LAMP1 signals. (f-h) Quantification of autophagosome-lysosome fusion in HeLa cells. Percentages of autolysosomes (positive for both mCherry-LC3 and LAMP1) to autophagosomes (positive for mCherry-LC3 and negative for LAMP1) were quantified. In (h), we analysed cells treated for 2 h with nocodazole before fixation, which dispersed the perinuclear lysosomal cluster (see Fig. 2a). (i) Autophagosomal and autolysosomal numbers in tfLC3-expressing cells after ARL8B overexpression and knockdown (Supplementary Fig. S5o shows representative cells.). In (f-i) we analysed 20 cells per group in three independent experiments. Values are means ± s.e.m of three independent experiments carried out in triplicate. *P0.05, **P0.01, ***P0.005 Student's t-test; other comparisons not significant (n.s.). Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "ARL8B: 55207"
  },
  {
    "caption": "A. Steady state protein levels in wild-type (WT) and Tim50-depleted mitochondria visualized by Western blotting and immunodetection with indicated antisera.",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "B. Jac1488 was imported into wild-type (WT) and Tim50-depleted mitochondria for indicated times and samples were treated with Proteinase K. p, precursor",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "C. Quantification of Jac1488 import into wild-type (WT) and Tim50-depleted mitochondria. The amount of imported protease-protected protein in WT mitochondria at 15 min was set to 100%; error bars indicate SEM (n=3).",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "D. [35S]Jac1 was imported into wild-type (WT) and Tim50-depleted mitochondria for indicated times and samples were treated with Proteinase K. p, precursor; m, mature.",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "E. Quantification of [35S]Jac1 import into wild-type (WT) and Tim50-depleted mitochondria. The amount of imported protease-protected protein in WT mitochondria at 15 min was set to 100%; error bars indicate SEM (n=3).",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "F. Steady state protein levels in wild-type (WT) and tim44-804 mitochondria visualized by Western blotting and immunodetection with indicated antisera.",
    "ncbi_link": "tim44: 854790"
  },
  {
    "caption": "G. pAmJac1680 was imported into wild-type (WT) and Tim50-depleted mitochondria for indicated times and samples treated with proteinase K. Samples were analyzed in 96-well format and by SDS-PAGE. The amount of imported protease-protected protein in WT mitochondria at 15 min was set to 100%; error bars indicate SEM (n=5 for 96-well plate analysis, n=4 for SDS-PAGE).",
    "ncbi_link": "Tim50: 856042"
  },
  {
    "caption": "G. Atp5488 (left panel) or [35S]Atp5 (right panel) were imported into wild-type and atp21∆ mitochondria for indicated times and in the presence or absence of a membrane potential (∆ψ). After proteinase K treatment, samples were solubilized in digitonin buffer and separated by BN-PAGE. Aliquots of the samples was analyzed by SDS-PAGE (lower panels). Subsequently proteins were visualized by fluorescence scanning or digital autoradiography. Complex V dimer, (CVD) and monomer (CVM). Prec., purified precursor ; p, precursor; m, mature protein.",
    "ncbi_link": "atp21: 851922"
  },
  {
    "caption": "A) Ten-fold serial dilutions from overnight cultures of wild-type and cdc14-1 cells dropped and grown on solid rich media or media containing MMS at 25, 28, 30 or 33ºC. Note that cdc14-1 cells exhibit growth sensitivity to MMS at 28ºC and 30ºC compared to wild-type cells.",
    "ncbi_link": "cdc14: 850585"
  },
  {
    "caption": "B) Ten-fold serial dilution from mid-log phase cultures of wild-type and cdc14-1 cells grown on solid rich media or media containing mock DMSO (as non-treated control), 4NQO, HU, phleomycin and benomyl at 30ºC. Note that cdc14-1 cells present a market sensitivity to all DNA damaged agents tested.",
    "ncbi_link": "cdc14: 850585"
  },
  {
    "caption": "C) Left panel: Schematic representation showing relevant genomic structure of the strain used to assess intra-chromosomal repair. The location of a MAT specific probe and the restriction endonuclease cleavage sites used for Southern blot analysis to detect repair product formation are indicated. Arrow depicts the localization of the double-strand break. Right panel: Physical analysis of intra-chromosomal repair in wild-type and cdc14-1 cultures at the semipermisive temperature. After DSB formation by the expression of the HO, glucose was added to repress it, thus allowing repair with HM donor sequences. Genomic DNA was digested with StyI, separated on agarose gel and blotted. Blots were hybridized with a probe corresponding to the MATa-distal sequence. A second probe for the actin gene was used to control the amount of genomic DNA loaded at each time-point. Immunoblot analysis of Rad53 during mating type switching experiments is shown. Coomassie blue staining is depicted as loading control. Graphs show quantification of gene conversion (GC) leading to the re-establishment of MATa or switching to MAT and DSB formation. The data was normalized with the actin loading control. Graphs show the mean ± S.D. from three independent experiments. Replicates were averaged and statistical significance of differences assessed by a 2-tailed unpaired Student t test.",
    "ncbi_link": "MATa: 
actin: 
MAT: 
cdc14: 850585"
  },
  {
    "caption": "A) Left panel: Schematic diagram displaying relevant genomic structure of the strains used to measure inter-chromosomal DNA repair efficiency. The location of a MAT specific probe and the restriction endonuclease cleavage sites used for Southern blot analysis to detect repair product formation are indicated. Note that crossover and non-crossover product have different restriction fragment sizes that can be differentiated in a Southern blot assay. Arrow depicts the localization of the double-strand break. Right panel: Physical analysis of wild-type and cdc14-1 mutant strains carrying the inter-chromosomal gene conversion assay. Cells were grown overnight before adding galactose at semipermisive temperature to induce HO expression, thus producing a DSB on chromosome V. Samples were taken at different time-points, genomic DNA was extracted, digested with EcoRI and analysed by Southern blot. Blots were hybridized with a MATa-only DNA sequence and an actin probe was used as loading control. Asterisk denotes an overexposed film to visualize crossover formation. Immunoblot of Rad53 was performed as previously described. Coomassie staining is shown as a control for loading. Graphs show the mean ± S.D. of gene conversion, DSB induction and crossover vs non-crossover ratio from three independent experiments. All data was normalized using actin as loading control. Replicates were averaged and statistical significance of differences assessed by a 2-tailed unpaired Student t test.",
    "ncbi_link": "MATa: 
actin: 
MAT: 
cdc14: 850585"
  },
  {
    "caption": "B) Left panel: Schematic representation depicting the genomic structure of the strains used to evaluate repair pathway choice. The location of a MAT specific probe and the restriction endonuclease cleavage sites used for Southern blot analysis to detect repair product formation are indicated. Note that the use of NHEJ or HR generates different product that can be recognized in Southern blots by the different disposition of the restriction sites for the endonucleases used. Arrow depicts the localization of the double-strand break. Right panel: Physical analysis of wild-type and cdc14-1 cells harbouring the repair pathway choice assay. Cells were grown overnight and HO induction was attained through addition of galactose for 1.5 hour at semipermisive temperature. After induction of the HO, glucose was added to repress the HO expression and samples were taken to analyse repair efficiency. DNA was extracted, digested with EcoRV, separated on agarose gels and blotted. Blots were hybridized with a probe corresponding to the MATa-only DNA sequence. A second probe to the HIS3gene was used to control the amount of genomic DNA loaded at each time-point. Graphs show quantification of mating type switching by gene conversion (HR), restoration of MATa (NHEJ) and the kinetics of the DSB induction. All data was normalized with the HIS3 gene. Graphs show the mean ± S.D. from three independent experiments. Replicates were averaged and statistical significance of differences assessed by a 2-tailed unpaired Student t test.",
    "ncbi_link": "MATa: 
HIS3: 
MAT: 
cdc14: 850585"
  },
  {
    "caption": "D) Live-cell imaging of Cdc14 localization in the presence of a non-reparable DSB at the MAT locus. Cells were grown overnight and the HO endonuclease was expressed by adding galactose to the media, thus producing a DSB on chromosome III. Cdc14, the SPB component Cnm67 and the DNA damage checkpoint protein Ddc2 (used as DSB reporter) were labelled with the green, red and cyan fluorescent proteins respectively. Micrographs display the maximum projection of 9 planes showing Cdc14 co-localizing with the DSB and the SPBs in response to DNA damage (arrows). Scale bar: 3μm. Graphs represent the percentage ± SD from three independents experiment of cells with nucleoplasmic Cdc14 along the HO endonuclease induction (left graph) and the percentage of Cdc14-SPB-DSB co-localization after 5h in galactose (right graph).",
    "ncbi_link": "MAT: "
  },
  {
    "caption": "B) Time-lapse experiments in living cells showing the efficiency of DSB-SPB interaction upon induction of a single DSB. Cnm67-CFP and Ddc2-RFP were used as SPB and DSB markers respectively. D1, D2 and D3 distances in wild-type and cdc14-1 cells were tracked using the maximum projection of three z-planes images at 15-seconds intervals over period of 7.5 minutes. A total of 32 time-lapses for each strain were measured. A representative picture is shown. Examples of cells defective in DSB-SPB interaction are marked with arrows. Scale bar: 3μm.",
    "ncbi_link": "cdc14: 850585"
  },
  {
    "caption": "C) An RFP-marked I-SceI recognition site is re-localized to the SPBs after expressing the endonuclease. Cells harbouring a TetO array adjacent to the I-SceI site and a plasmid containing the endonuclease under the control of the galactose promoter were grown overnight in SC-Ade prior galactose induction. To check reproducibility with previous results a Rad52-CFP was used. Cnm67 was labelled with the GFP to be used as SPB reporter. D1, D2 and D3 distances were measured in wild-type and cdc14-1 mutants before and after endonuclease expression by using both TetI-RFP and Rad52-CFP foci using the maximum projection of nine z-planes images. Graphs represent the average of three independent experiments. P values were calculated using a 2-tailed unpaired Student t test. A representative picture of a wild-type strain depicting TetI-Rad52-SPB interaction is shown. Scale bar: 3μm.",
    "ncbi_link": "TetO: 
cdc14: 850585"
  },
  {
    "caption": "D) DSB-SPB tethering requires the N-terminus domain of Mps3. Cells expressing a wild-type Mps3, a mps3Δ2-64 and a mps3Δ75-150 fused to the RFP as the sole source of the protein were scored for their ability to enhance DSB-SPB tethering in both wild-type and cdc14-1 backgrounds. Ddc2-YFP was used as DSB reporter. Measurements were carried out using a maximum projection of nine z-planes images. Graphs represent the average distribution of D1, D2 and D3 of three independent experiments. At least 100 cells for each experiment were scored. P values were calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "cdc14: 850585
mps3: 853434
Mps3: 853434"
  },
  {
    "caption": "E) DSB-SPB interaction involves a proficient DNA damage checkpoint activation. D1, D2 and D3 distances were scored in wild-type, sml1Δ and sml1Δ rad53Δ backgrounds using Ddc2-GFP and Spc110-RFP as DSB and SPB markers respectively. Measurements were performed by using a maximum projection of nine z-planes images. Graphs denote the average distribution of D1, D2 and D3 from three independent experiments where at least 100 cells for each sample were scored. P values were calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "rad53: 855950
sml1: 854945"
  },
  {
    "caption": "A) Identification of Cdc14 phospho-targets during the DNA damage response by mass spectrometry analysis. Wild-type and cdc14-1 cells were grown overnight and blocked in G2/M by using nocodazole to avoid cell cycle-dependent changes in protein phosphorylation between both strains. After the block was attained, cells were transferred to 37ºC for 45 minutes to deplete Cdc14 activity prior HO induction by galactose addition for 4h. Differential phosphorylation of phospho-peptides detected between the wild-type and cdc14-1 were grouped into broad categories depending on the molecular function of the proteins. The table includes the DNA damage and checkpoint-related proteins with Cdc14-dependent hyper-phosphorylated status and the relative ratio between the wild-type and cdc14-1 during the DNA damage response. Red and blue indicate relative amount of the residue phosphorylation between both strains (Red, high; Blue, low).",
    "ncbi_link": "Cdc14: 850585
cdc14: 850585"
  },
  {
    "caption": "B) Cdc14 dephosphorylates Spc110 in response to a DSB. Spc110 was tagged with the 6HA epitope in wild-type, cdc14-1 and spc110S36-91A backgrounds. Cells were grown overnight in raffinose-containing media and supplemented with galactose to induce HO expression. Samples were collected at each time-point indicated. Proteins were TCA extracted, separated on Phos-Tag containing gels and blotted. Coomassie staining is shown as loading control.",
    "ncbi_link": "cdc14: 850585
spc110: 851957"
  },
  {
    "caption": "D) The canonical FEAR pathway is required for Spc110 dephosphorylation during the DNA damage response. Spc110 was labelled with the 3HA tag in both wild-type and esp1-1 background strains. Cells were grown overnight in raffinose-containing media and supplemented with galactose to induce the HO expression. Samples were collected at each time-point indicated. Proteins were TCA extracted, separated on Phos-Tag containing gels and blotted. Coomassie staining is shown as a control for loading.",
    "ncbi_link": "esp1: 852990"
  },
  {
    "caption": "A) Time-lapse experiments of living cells harbouring a non-reparable DSB were carried out after expressing the HO endonuclease in wild-type and cdc14-1 mutant cells. Spc110-RFP was used as SPB reporter and Tub1-GFP was used as tubulin marker. Three z-planes images every 5-second intervals over a period of 5 minutes were captured and used to quantify the average SPB track length and velocity using Spc110-RFP as SPB marker. At least 100 cells were scored.A representative maximum projection image is depicted. Scale bar: 3μm.",
    "ncbi_link": "cdc14: 850585"
  },
  {
    "caption": "A) A Western blot is shown to confirm the equal amount of Tub1-GFP in both wild-type and cdc14-1 backgrounds. Coomassie blue staining is shown as loading control.",
    "ncbi_link": "cdc14: 850585"
  },
  {
    "caption": "B) The steady state phosphorylation of Spc110 is required to maintain spindle polarity in response to DNA damage. Wild-type, cdc14-1 and spc110S36-91A cells expressing Spc110-RFP were scored for their ability to maintain spindle polarity at the axial plane of the cell upon induction of a single DSB induced by the HO endonuclease. A maximum projection of nine z-planes was used to score the cells. At least 100 cells from three independent experiments were scored. Graph represents the percentage ± SD of cells with oriented/miss-oriented SPBs with respect to the axial plane of the cell. P value was calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "cdc14: 850585
spc110: 851957"
  },
  {
    "caption": "C) The asymmetric loading of dynein into astral MTs emanating from the daughter SPB is affected in cdc14-1 and spc110S36-91A cells during the DNA damage response. Dynein distribution on astral MTs emerging from each SPB was scored by using Dyn1-GFP in strains containing Spc110-RFP. Graph represents the percentage ± SD of cells grouped into three categories depending on the pattern of dynein distribution on astral MTs: Type1, Dynein is exclusively loaded on astral MTs emerging from the daughter SPB; Type 2, Dynein is equally loaded on astral MTs emanating from both SPBs; Type 3, Dynein is absent from astral MTs. At least 100 cells from three independent experiments were scored. A representative picture showing the three patterns is included. Scale bar: 3μm.",
    "ncbi_link": "cdc14: 850585
spc110: 851957"
  },
  {
    "caption": "B) Physical analysis of wild-type cells containing the repair pathway choice assay described in Fig 2B. The diagram with the genomic information, the restriction enzymes used and the location of the probe are shown. Cells were synchronized in G1 by using the α-factor pheromone and released into fresh media for 1 hour. Induction of HO expression was attained by adding galactose for 2 hours. After formation of the DSB, glucose was added to repress the HO in the presence of nocodazole or mock DMSO and samples were taken to analyse the kinetics of the repair. DNA was extracted, digested with EcoRV, separated on agarose gels and blotted. Both probes for the MATa-distal sequence and the HIS3 gene (as loading control) were used. Graphs show the quantification of MATa restoration (NHEJ), mating type switching by gene conversion (HR), and DSB kinetics formation. All data were normalized with the HIS3 gene. Graphs show the mean ± S.D. from three independent experiments. P values were calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "MATa: 
HIS3: "
  },
  {
    "caption": "A) Growth sensitivity to MMS and phleomycin of a Cdk phospho-deficient mutant of Spc110. Ten-fold serial dilutions from overnight cultures of wild-type, spc110S36-91A and a cdc14-1 cells grown on solid rich media containing mock DMSO, MMS or Phleomycin at 30ºC.",
    "ncbi_link": "cdc14: 850585
Spc110: 851957
spc110: 851957"
  },
  {
    "caption": "B) Diagram showing the genomic background and the approximation used to measure DSB-SPB interaction. Spc110 and spc110S36-91A were labelled with the RFP in a background containing Ddc2-GFP as DSB reporter. D1: inter-SPB distance; D2: DSB distance to proximal SPB; D3: DSB distance to distal SPB. At least 100 cells from three independent experiments were scored using the maximum projection of nine z-planes. Graph shows the mean ± S.D. P values were calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "C) Time-lapse experiments of living cells expressing the HO endonuclease in wild-type and spc110S36-91A mutants cells. Five z-planes every 5-second intervals over a period of 5 minutes were captured. Quantifications were made using the average SPB track length and velocity of at least 100 cells. Spc110 and spc110S36-91A were labelled with the RFP and used as SPB reporter.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "D) Southern blot of wild-type and spc110S36-91A mutant harbouring the inter-chromosomal gene conversion assay portrayed. An overnight culture was induced by adding galactose at 32ºC to express the HO endonuclease. Samples were collected at different time-points, genomic DNA was extracted, digested with EcoRI and analysed by Southern blot. Blots were probed with a MATa-only and actin (for loading control) DNA sequences. Graphs show quantification of gene conversion, DSB induction and crossover vs non-crossover ratio. All data were normalized using the actin signal. Graphs represent the mean ± S.D. from three independent experiments. P values were calculated using a 2-tailed unpaired Student t test. Asterisk denotes an overexposed film to visualize the formation of crossover products.",
    "ncbi_link": "MATa: 
actin: 
spc110: 851957"
  },
  {
    "caption": "D) Southern blot of wild-type and spc110S36-91A mutant harbouring the inter-chromosomal gene conversion assay portrayed. An overnight culture was induced by adding galactose at 32ºC to express the HO endonuclease. Samples were collected at different time-points, genomic DNA was extracted, digested with EcoRI and analysed by Southern blot. Blots were probed with a MATa-only and actin (for loading control) DNA sequences. FACS profiles for DNA content are included. Graphs show quantification of gene conversion, DSB induction and crossover vs non-crossover ratio. All data were normalized using the actin signal. Graphs represent the mean ± S.D. from three independent experiments. P values were calculated using a 2-tailed unpaired Student t test. Asterisk denotes an overexposed film to visualize the formation of crossover products.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "A) DNA damage sensitivity to MMS and phleomycin of a Cdk phospho-mimic mutant of Spc110. Ten-fold serial dilutions from mid-log phase cultures of wild-type, spc110S36-91A and spc110S36-91D cells grown on solid rich media containing mock DMSO, MMS or Phleomycin at 30ºC.",
    "ncbi_link": "Spc110: 851957
spc110: 851957"
  },
  {
    "caption": "B) Schematic representation of the genomic background and the approximation used to measure DSB-SPB tethering. Wild-type Spc110 and spc110S36-91D were labelled with the RFP. Ddc2 was tagged with the GFP to be used as DSB reporter. D1: inter-SPB distance; D2: DSB distance to proximal SPB; D3: DSB distance to distal SPB. At least 100 cells from three independent experiments were scored using the maximum projection of nine z-planes. Graph shows the mean ± S.D. P values were calculated using a 2-tailed unpaired Student t test.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "C) Time-lapse experiments of living cells after induction of the HO endonuclease in wild-type and spc110S36-91D cells. Three z-planes every 10-second intervals over a period of 5 minutes were captured to measure the average SPBs track length and velocity. Spc110 and spc110S36-91D were labelled with the RFP and used to measured SPBs kinetics. At least 100 cells from three independent experiments were scored.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "D) Southern blot of wild-type and spc110S36-91D mutant bearing the inter-chromosomal gene conversion assay depicted. Mid-log phase cells were HO-induced at 32ºC by adding galactose to the media. Samples were collected at different time-points and the genomic DNA was extracted. Preps were digested with EcoRI and analysed by Southern blot. Blots were hybridized with MATa-only and actin probes. Graphs show quantification of gene conversion, DSB induction and crossover vs non-crossover ratio. All data were normalized using the actin signal. Graphs represent the mean ± S.D. from three independent experiments. P values were calculated using a 2-tailed unpaired Student t test. Asterisk denotes an overexposed film to visualize the formation of crossover products.",
    "ncbi_link": "MATa: 
actin: 
spc110: 851957"
  },
  {
    "caption": "D) Southern blot of wild-type and spc110S36-91D mutant bearing the inter-chromosomal gene conversion assay depicted. Mid-log phase cells were HO-induced at 32ºC by adding galactose to the media. Samples were collected at different time-points and the genomic DNA was extracted. Preps were digested with EcoRI and analysed by Southern blot. Blots were hybridized with MATa-only and actin probes. FACS profiles for DNA content are displayed. Graphs show quantification of gene conversion, DSB induction and crossover vs non-crossover ratio. All data were normalized using the actin signal. Graphs represent the mean ± S.D. from three independent experiments. P values were calculated using a 2-tailed unpaired Student t test. Asterisk denotes an overexposed film to visualize the formation of crossover products.",
    "ncbi_link": "spc110: 851957"
  },
  {
    "caption": "(H) HeLa cells transfected with GFP-PHD3X or GFP-PHD3X Znmut and RFP-LC3 for 16 hr were left in complete media (basal) or starvation media (HBSS) for 1 hr, then fixed and imaged on a confocal microscope. Empty arrowheads indicate PHD3X single-labeled structures, while filled arrowheads indicate PHD3X-LC3- and PHD3X-ATG16-positive structures. Bar, 10 μm.",
    "ncbi_link": "PHD3X: 3622
LC3: 84557"
  },
  {
    "caption": "(I) HeLa cells transfected with GFP-PHD3X and RFP-LC3 for 16 hr were left in HBSS for 1 hr, then fixed and imaged on Elyra superresolution microscope. Final visualization was performed in Volocity 6.3 software using isosurface rendering of selected cropped regions of the data sets. Note that this rendering means that vesicles positive for green and red do not look yellow but have green and red on the surface. Representative cropped regions from different cells are shown. Bar, 1.13 μm. See also Figure S1.",
    "ncbi_link": "PHD3X: 3622"
  },
  {
    "caption": "(D and E) HeLa cells transiently transfected with Strawberry-ATG16L1 were treated with YM-201636 (100 nM, 2 hr) in HBSS, then fixed and stained for endogenous WIPI-2. Bar, 10 μm. (E) Quantification of ATG16L1 and WIPI2 structures per cell, n = 20 cells (mean ± SEM; n = 3 independent experiments; ∗∗∗p < 0.001, t test).",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(G) HeLa cells transfected with GFP-PHD3X and Strawberry-ATG16L1 for 16 hr were left in HBSS for 1 hr, then fixed and imaged on Elyra superresolution microscope. Final visualization was performed as previously described. Bar, 1.13 μm.",
    "ncbi_link": "ATG16L1: 55054
PHD3X: 3622"
  },
  {
    "caption": "(A and B) Western blot analysis of LC3-II and tubulin levels and quantification of LC3-II/tubulin ratio in HeLa cells transfected for 5 days with two rounds of control, PI5P4K2A, 2B, or 2C siRNA either left untreated or treated with BAF (200 nM, 16 hr) (mean ± SEM).",
    "ncbi_link": "PI5P4K2A: 5305"
  },
  {
    "caption": "(D) Western blot analysis of free ATG12 and ATG5-ATG12 complex levels with anti-HA antibody in HeLa cells treated with control, PI5P4K2A, 2B, and 2C siRNA and transfected with HA-ATG12 and ATG5 for the last 16 hr (mean ± SEM).",
    "ncbi_link": "PI5P4K2A: 5305"
  },
  {
    "caption": "(E and F) HeLa cells transfected with GFP-PI5P4K2A, 2B, 2C, or catalytic-dead PI5P4K2C along with RFP-LC3 for 16 hr (E) or 30 hr (F) were fixed and imaged on a confocal microscope. Bar, 10 μm.(G) Quantification of cells (percentage of total) showing more than ten autophagic vesicles (RFP-LC3 vesicles) in the different conditions from (F) is shown in the graph; n = 200 cells (mean ± SEM). See also Figure S3.",
    "ncbi_link": "PI5P4K2A: 5305
PI5P4K2C: 79837"
  },
  {
    "caption": "(C) HeLa cells treated with PI5P4K2A or PI5P4K2C siRNA for 5 days or with pCMV-PI5P4K2C overexpression construct for 48 hr were transfected with EGFP-httQ74 for the last 48 hr. Percentage of cells with EGFP-positive aggregates is shown in the graph; n = 500 cells (mean ± SEM). Cells expressing control vector typically have 25% of aggregates and we set the control at 100% to enable comparison and statistics from independent experiments.",
    "ncbi_link": "pCMV: 
httQ74: 3064
PI5P4K2A: 5305
PI5P4K2C: 79837"
  },
  {
    "caption": "(D and E) Percentage of cells with EGFP-positive aggregates was scored in HEK293 cells treated with PI5P4K2C siRNA for 5 days and cotransfected with EGFP-httQ74 for the last 48 hr (D), or in COS7 and SKNSH cells (E), transfected with PI5P4K2C plasmid together with EGFP-httQ74 for the last 48 hr.",
    "ncbi_link": "httQ74: 3064
PI5P4K2C: 79837"
  },
  {
    "caption": "(F and G) WT (Atg5+/+) or autophagy-deficient cells lacking the key autophagy gene Atg5 (Atg5−/−) MEFs were treated with PI5P4K2C siRNA (5 days) or PI5P4K2C plasmid (48 hr) together with EGFP-httQ74 for 48 hr. The percentages of transfected cells with EGFP-httQ74 aggregates were assessed and shown in the graph; n = 500 cells (mean ± SEM). Representative confocal images are shown in (G). See also Figures S3 and S4.",
    "ncbi_link": "Atg5: 11793
httQ74: 15194
PI5P4K2C: 79837"
  },
  {
    "caption": "(D) HeLa cells transfected with HA-ATG12 and ATG5 treated with 200 nM Wm as in (A) and subjected to western blot analysis with anti-HA antibody to detect free ATG12 and the ATG5-ATG12 complex (mean ± SEM). ATG5-ATG12 conjugation was checked for endogenous proteins in the same conditions using an anti-ATG12 antibody (bottom).",
    "ncbi_link": "ATG12: 9140
ATG5: 11793"
  },
  {
    "caption": "(E and F) Western blot analysis of LC3-II and tubulin levels and quantification of LC3-II/tubulin ratio in HeLa cells transfected with control, PI5P4K2A, 2B, and 2C siRNA and treated with Wm (200 nM, 2 hr in the presence of BAF) (mean ± SEM).",
    "ncbi_link": "PI5P4K2A: 5305"
  },
  {
    "caption": "(G and H) Western blot analysis of free ATG12 and ATG5-ATG12 complex levels with anti-HA antibody in HeLa cells treated with control, PI5P4K2A, 2B, and 2C siRNA, transfected with HA-ATG12 and ATG5 for last 16 hr and treated with Wm for 2 hr (mean ± SEM).",
    "ncbi_link": "ATG12: 9140
ATG5: 11793
PI5P4K2A: 5305"
  },
  {
    "caption": "(I) HeLa cells stably expressing GFP-LC3 treated with control, PI5P4K2A, 2B, and 2C siRNA, were pretreated with Wm for 2 hr in complete medium and then shifted in HBSS media for 2 hr (in the presence of Wm) (mean ± SEM).",
    "ncbi_link": "PI5P4K2A: 5305"
  },
  {
    "caption": "(J and K) HeLa cells stably expressing GFP-LC3 were transfected for 30 hr with myc-tagged empty vector, myc-MTMR3WT, and myc-MTMR3C413S, incubated for 4 hr in HBSS in the presence of BAF and in the presence or absence of Wm. Cells were fixed, stained with anti-myc antibodies, and imaged by confocal microscope. Asterisks indicate transfected cells. Quantification of numbers of GFP-LC3vesicles per cell is shown in (K) (mean ± SEM).",
    "ncbi_link": "MTMR3: 8897"
  },
  {
    "caption": "(L and M) HeLa cells transfected with GFP-PI5P4K2A, 2B, 2C, and RFP-LC3 for 30 hr were loaded with 10 μM PI(3)P for 1 hr in complete medium, and then fixed and imaged on confocal microscope. Bar, 10 μm. Quantification of cells (percentage of total) showing more than 10 RFP-LC3 vesicles in the different conditions from (J) is shown in (M); n = 200 cells (mean ± SEM). See also Figure S5.",
    "ncbi_link": "PI5P4K2A: 5305"
  },
  {
    "caption": "(A) HeLa cells transfected with GFP-WIPI2B or GFP-DFCP1 preloaded with indicated concentrations of PI(5)P for 1 hr, starved in HBSS for 1 hr, and then incubated with Wm in HBSS were tracked by time-lapse microscopy for 10 min after the addition of Wm. Quantification of WIPI2B or DFCP1vesicles (percentage of those at the starting time [T0]) during the treatments are shown in the graphs.",
    "ncbi_link": "WIPI2B: 26100
DFCP1: 53349"
  },
  {
    "caption": "(B-D) HeLa cells treated with control, PI5P4K2A, 2B, and 2C siRNA were transfected with GFP-WIPI2B (B), GFP-WIPI2D (C), or GFP-DFCP1 (D); starved in HBSS (1 hr); and then incubated with Wm in HBSS. WIPI2 or DFCP1 structures were tracked and quantified as in (A).",
    "ncbi_link": "PI5P4K2A: 5305
WIPI2B: 26100
DFCP1: 53349"
  },
  {
    "caption": "(F-H) Cell extracts from HeLa cells stably expressing GFP-WIPI2B were incubated for 3 hr with PI(5)P-containing liposomes (F and H) or PI(3)P-containing liposomes (G and H) before a pull-down experiment using the indicated beads. PS-containing liposomes were used as internal controls for both competition assays in (F and G).",
    "ncbi_link": "WIPI2B: 26100"
  },
  {
    "caption": "(I) Lysates from HeLa cells stably expressing GFP-WIPI2B WT and GFP-WIPI2B FTTG mutant were incubated with agarose beads coated with PI(5)P and PI(3)P, eluted with SDS-PAGE sample buffer, and recovered proteins were assessed by western blotting using antibodies against GFP. See also Figure S6.",
    "ncbi_link": "WIPI2B: 26100"
  },
  {
    "caption": "(D) HeLa cells transfected with GFP-PHD3X and Strawberry-ATG16L1 for 16 hr were left in complete media (basal) or glucose-free media (glucose free) for 4 hr in the presence or absence of 100 nM YM-201636, then fixed and imaged on a confocal microscope.",
    "ncbi_link": "ATG16L1: 55054
PHD3X: 3622"
  },
  {
    "caption": "(E and F) HeLa cells transfected with GFP-PI5P4K2A, 2B, 2C, or PI5P4K2C catalytic dead and RFP-LC3 for 30 hr (E) were starved for glucose for 4 hr, then fixed and imaged on a confocal microscope. Bar, 10 μm. (F) Quantification of cells (percentage of total) showing more than ten autophagic vesicles (RFP-LC3 vesicles) in the different conditions from (F) is shown in the graph; n = 200 cells (mean ± SEM).",
    "ncbi_link": "LC3: 84557
PI5P4K2A: 5305
PI5P4K2C: 79837"
  },
  {
    "caption": "(G) HeLa cells treated with CTR or MTMR3 siRNA for 5 days were transfected for the last 16 hr with GFP-PHD3X, Strb-ATG16L1, and myc-MTMR3 WT. Cells were starved for glucose for 4 hr, then fixed, stained with anti-myc antibodies, and imaged on a confocal microscope. Bar, 10 μm.",
    "ncbi_link": "ATG16L1: 55054
PHD3X: 3622
MTMR3: 8897"
  },
  {
    "caption": "(H) HeLa cells transfected for 16 hr with GFP-PHD3X and Strb-ATG16L1 were starved for 4 hr in HBSS or glucose-free media, then fixed, stained for PI(3)P antibodies, and imaged on a confocal microscope. Bar, 10 μm. See also Figure S7.",
    "ncbi_link": "ATG16L1: 55054
PHD3X: 3622"
  },
  {
    "caption": "(A and B) Tau increased β-catenin acetylation (Ace-β-cat) measured by immunoprecipitation using anti-β-cat, or Western blotting using anti-β-cat, anti-acetylated lysine (Ace-lys) and HT7 (probes specifically human total Tau). HEK293 cells transiently transfected with wildtype Tau40 (Tau) or the empty vector (Vec) (n = 3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec Data were analyzed by Student's t test",
    "ncbi_link": "Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(C and D) β-cat mutation at K49 (K49R) but not K19 (K19R) abolished Tau-induced acetylation. HEK293 cells were co-transfected with eGFP-β-cat (WT, or K19R, or K49R, or K19R/K49R) and Tau or the empty vector for 48 h, and then immunoprecipitated using anti-GFP and Western blotting using anti-β-cat, anti-Ace-lys and HT7 (n = 3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs β-cat WT (D) ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs β-cat WT plus Tau (D) ; &&, P<0.01, &&&, P<0.001 vs β-cat K19R plus Tau (D); the absence of asterisk indicates that the difference is not significant. Data were analyzed by one-way ANOVA",
    "ncbi_link": "eGFP: 
β-cat: 1499
Tau: 4137"
  },
  {
    "caption": "(E and F) The increased β-cat (K49) acetylation was detected in the hippocampal extracts of human Tau transgenic mice (Tau+) compared with the endogenous Tau knockout mice (Tau-), measured by Western blotting using acetylation site-specific antibody (Ace-β-cat-K49); arrowhead in panel E denoted nonspecific band identified by molecular weight. The remarkably increased levels of phosphorylated Tau at Ser199 (pS199) and AT8 epitopes were detected in Tau+ mice (at least 3 mice per group were used). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs vs Tau- (F) Data were analyzed by Student's t test",
    "ncbi_link": "Tau: 4137
Tau: 17762"
  },
  {
    "caption": "(G and H) K18 deletion of Tau (Tau-k18(-)) attenuated Tau-induced β-cat acetylation. HEK293 cells were transfected with empty Vec, or Tau40 or Tau-k18(-) for 48 h, and the ace-β-cat was measured by immunoprecipitation using anti-β-cat and Western blotting using anti-ace-lys, anti-β-cat, and Tau5 (detecting total Tau; n = 3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Tau (H) Data were analyzed by one-way ANOVA",
    "ncbi_link": "Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(M and N) Expressing pseudo-phosphorylated Tau (TauS199E) further increased the K49-acetylation of β-catenin. N2a cells were transiently transfected with Vec, Tau40 or TauS199E for 48 h, levels of K49-acetylated β-cat, total β-cat and total Tau were detected by Western blotting (n=3 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs β-cat WT plus vs Tau (N) Data were analyzed by one-way ANOVA",
    "ncbi_link": "Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(O and P) Inhibiting acetyltransferases CBP/P300 by TPOP146 (134 nM) or PCAF by L-45 (126 nM) for 24 h did not significantly decrease the K49-acetylated β-cat level in Tau-overexpressing N2a cells (n=3 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec Data were analyzed by one-way ANOVA",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(D and E) Mutation of β-cat K49 abolishes its acetylation by Tau. Both myc-Tau40 and eGFP-β-cat were purified from HEK293 cells (using anti-GFP or anti-Myc beads) (D), or both from E. coli (E) (n = 3 from three independent experiments).",
    "ncbi_link": "eGFP: "
  },
  {
    "caption": "(A and B) Expressing Tau inhibited β-cat ubiquitination in HEK293 cells, measured by immunoprecipitation using antibody against β-cat and Western blotting using anti- ubiquitination (anti-Ub) and anti-β-cat, respectively (n = 3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Vec (B) Data were analyzed by Student's t test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(C and D) Overexpressing Tau inhibited β-cat ubiquitination in hippocampi of Tau transgenic mice, measured by immunoprecipitation using anti-Ub and Western blotting using anti-β-cat, respectively (n = 3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Tau- (D) Data were analyzed by Student's t test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(E and F) Expressing Tau-k18(-) attenuated Tau-induced β-cat elevation. HEK293 cells were transfected with Vec, or Tau-40, or Tau-k18(-) for 24 h, and then were treated with Chx for 12 h or 24 h, followed by Western blotting. β-cat protein level was normalized to β-actin (n=4 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Tau (F) Data were analyzed by Two-way repeated-measures ANOVA",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(G and H) K49 acetylation of β-cat inhibited its ubiquitination. HEK293 cells were co-transfected with HA-ubiquitin and GFP-β-cat or pseudo-acetylated K49-β-catenin (K49Q), and then β-cat was immunoprecipitated by anti-GFP and blotted by anti-Ub and anti-β-cat (n=3 from three independent experiments). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs β-cat WT Data were analyzed by Student's t test.",
    "ncbi_link": "GFP: 
HA: 
β-cat: 1499
β-catenin: 1499"
  },
  {
    "caption": "(I and J) K49 acetylation of β-cat inhibited its degradation. HEK293 cells were transfected with β-cat WT or K49Q for 24 h, and then treated with cycloheximide (Chx, 100 μg/ml) for 12 h or 24 h (n=4 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs β-cat WT Data were analyzed by Two-way repeated-measures ANOVA",
    "ncbi_link": "β-cat: 1499"
  },
  {
    "caption": "β-cat mutation at K49 (K49R) restored the degradation of β-catenin. HEK293 cells were transfected with β-cat WT or co-transfected with β-cat WT and Tau40, or co-transfected with β-cat K49R and Tau40 for 24 h, and then treated with cycloheximide (Chx, 100 μg/ml) for 12 h or 24 h (n=4 biological replicates each group).",
    "ncbi_link": "β-cat: 1499
Tau40: 4137"
  },
  {
    "caption": "β-cat mutation at K49 (K49R) restored the degradation of β-catenin. HEK293 cells were transfected with β-cat WT or co-transfected with β-cat WT and Tau40, or co-transfected with β-cat K49R and Tau40 for 24 h, and then treated with cycloheximide (Chx, 100 μg/ml) for 12 h or 24 h (n=4 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs Tau+β-cat WT (L) Data were analyzed by Two-way repeated-measures ANOVA",
    "ncbi_link": "β-cat: 1499
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(M and N) K49 acetylation of β-cat inhibited its phosphorylation at N-terminal domain. HEK293 cells were transfected with GFP-vec, or eGFP-β-cat (WT) or K49Q for 48 h, then treated with wortmannin (WO, 1 μM) plus GF109203X (GFX, 1 μM) to activate GSK-3β for 1 h followed by Western blotting (n=3 biological replicates each group). Data information: Data are presented as mean ± SEM; *, P<0.05; **, P<0.01; ***, P<0.001 vs β-cat WT plus WO/GFX (N). data in (N) was analyzed by one-way ANOVA.",
    "ncbi_link": "eGFP: 
GFP: 
β-cat: 1499"
  },
  {
    "caption": "(A and B) Expressing Tau-k18(-) abolished its effect on β-cat K49-acetylation and c-cas-3 (cleaved caspase-3). N2a cells were transfected with Vec, or Tau40, or Tau-k18(-) for 48 h, and then treated with 0.5 μM staurosporine (STP, an apoptotic inducer) for 4 h, followed by Western blotting (n=3 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs vec (B) #, P<0.05, ##, P<0.01, ###, P<0.001 vs Vec plus STP (B) ; $$$, P<0.001 vs Tau plus STP (B) Data were analyzed by one-way ANOVA.",
    "ncbi_link": "Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "Expressing Tau-k18(-) or Tau-2CA abolished its anti-apoptotic function. ; N2a cells, transfected with myc-Vec, or myc-Tau40, or myc-Tau-k18(-), or myc-Tau-2CA for 48 h, were then treated with 0.5 μM STP for 4 h followed by flow cytometry using Annexin-FITC (C) Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Tau plus STP Data were analyzed by one-way ANOVA.",
    "ncbi_link": "myc: 
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "Expressing Tau-k18(-) or Tau-2CA abolished its anti-apoptotic function. N2a cells, transfected with eGFP-Vec, or eGFP-Tau40, or eGFP-Tau-k18(-), or Tau-2CA for 48 h, were then treated with 0.5 μM STP for 4 h followed by co-staining with c-cas-3 (red) (D In panel D (middle row), the Tau expression (white arrowheads) was largely not co-localized with c-casp-3 (yellow arrowheads) in the same visual field (n=4~8 biological replicates each group; scale bar, 10 μm).",
    "ncbi_link": "eGFP: 
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "Expressing Tau-k18(-) or Tau-2CA abolished its anti-apoptotic function. N2a cells, transfected with eGFP-Vec, or eGFP-Tau40, or eGFP-Tau-k18(-), or Tau-2CA for 48 h, were then treated with 0.5 μM STP for 4 h followed by co-staining with c-cas-3 (red) The apoptotic rate (E) was presented as the ratio of yellow (c-casp-3 and GFP co-stained) to green (the total GFP-expressing cells) staining. Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Tau plus STP Data were analyzed by one-way ANOVA.",
    "ncbi_link": "eGFP: 
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "Expressing Tau-k18(-) or Tau-2CA abolished its anti-apoptotic function. N2a cells, transfected with myc-Vec, or myc-Tau40, or myc-Tau-k18(-), or myc-Tau-2CA for 48 h, were then treated with 0.5 μM STP for 4 h followed by CCK8 assay (F). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Tau plus STP ♧♧♧, P<0.001 vs vec Data were analyzed by one-way ANOVA.",
    "ncbi_link": "myc: 
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(G) Non-acetylation modifiable mutation of β-cat at K49 (K49R), not K19 (K19R), abolished the anti-apoptotic effect of Tau. N2a cells were co-transfected with Tau40 and β-cat WT, or K49R, or K19R for 48 h, and then treated with 0.5 μM STP for 4 h. The cell viability was measured by CCK8 assay (n=8 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Vec plus STP ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs vs β-cat + Vec plus STP (G) ; $$$, P<0.001 vs β-cat + Tau plus STP (G) ; &&&, P<0.001 vs β-cat K49R+ Tau plus STP (G). ♧♧♧, P<0.001 vs vec Data were analyzed by one-way ANOVA.",
    "ncbi_link": "β-cat: 12387
Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "(H) Expressing β-cat K49Q most significantly increased cell viability. N2a cells were transfected with β-cat WT or K49R or K49Q or the empty Vec for 48 h, and then treated with 0.5 μM STP for 4 h. The cell viability was measured by CCK8 assay (n=8 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Vec plus STP ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs β-cat plus STP (H), ; $$$, P<0.001 vs β-cat K49Q plus STP (H) ♧♧♧, P<0.001 vs vec Data were analyzed by one-way ANOVA.",
    "ncbi_link": "β-cat: 12387"
  },
  {
    "caption": "(I) Overexpressing Ser199-phosphorylation mimic Tau (TauS199E) further augmented cell viability. N2a cells were transfected with empty vec, Tau40 or TauS199E for 48h and then treated with 0.5 μM STP for 4 h. The cell viability was measured by CCK8 assay (n=8 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Vec plus STP ; #, P<0.05, ##, P<0.01, ###, P<0.001 vs vs Tau plus STP (I) Data were analyzed by one-way ANOVA.",
    "ncbi_link": "Tau: 4137
Tau40: 4137"
  },
  {
    "caption": "Expressing β-cat K49Q increased its nuclear translocation. HEK293 cells were transfected with eGFP-β-cat WT or K49Q for 48 h, and then β-cat protein level in different fractions was measured by Western blotting",
    "ncbi_link": "eGFP: 
β-cat: 1499"
  },
  {
    "caption": "Expressing β-cat K49Q increased its nuclear translocation. HEK293 cells were transfected with eGFP-β-cat WT or K49Q for 48 h, and then β-cat protein level in different fractions was measured by Western blotting Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs β-cat WT (C) Data were analyzed by Student's t test",
    "ncbi_link": "eGFP: 
β-cat: 1499"
  },
  {
    "caption": "Expressing β-cat K49Q increased its nuclear translocation. HEK293 cells were transfected with eGFP-β-cat WT or K49Q for 48 h and immunofluorescent labeling using a laser scanning confocal microscope (D). The nuclei (blue) was stained by DAPI (n=3 from three independent experiments, scale bar, 2 μm).",
    "ncbi_link": "eGFP: 
β-cat: 1499"
  },
  {
    "caption": "(E) Expressing β-cat K49Q further increased its transcription activity measured by dual Topflash/Fopflash reporter luciferase assay after transient transfection of β-cat WT, or K49Q, or Vec in HEK293 cells for 48 h, and the luciferase activity was normalized by β-cat WT or K49Q protein level (n=7 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Vec ; ##, P<0.01, ###, P<0.001 vs β-cat WT Data were analyzed by one-way ANOVA",
    "ncbi_link": "β-cat: 1499"
  },
  {
    "caption": "(F) Expressing Tau-k18(-) abolished Tau-induced upregulation of mRNA levels of survival genes (bcl2 and survivin) and dkk1 (downstream of Wnt signaling) in N2a cells measured by Q-PCR (n=6~9 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Tau (F Data were analyzed by one-way ANOVA",
    "ncbi_link": "bcl2: 12043
survivin: 11799
dkk1: 13380
Tau: 4137"
  },
  {
    "caption": "(G) Expressing Tau-k18(-) or Tau-2CA abolished Tau-induced Wnt/β-catenin transcriptional activation measured by dual reporter luciferase activity assay in HEK293 cells (n=7 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs vs Tau Data were analyzed by one-way ANOVA",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(H) Expressing phosphor-mimic TauS199E (TauS199E) further increased the transcription activity of Wnt/TCF/LEF1 by Tau in HEK293 cells (n=7 biological replicates each group). Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Vec ; ##, P<0.01, ###, P<0.001 vs Tau (H). Data were analyzed by , one-way ANOVA",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "The increased mRNA levels of bcl2, survivin and dkk1 in the AD brains compared with the age-/sex-matched controls detected by Q-PCR (n=7 each group) Data information: Data are expressed as mean ± SEM, *, P<0.05; **, P<0.01, ***, P<0.001 vs Ctrl (I) Data were analyzed by Student's t test",
    "ncbi_link": "bcl2: 596
survivin: 332
dkk1: 22943"
  },
  {
    "caption": "The increased mRNA levels of bcl2, survivin and dkk1 in the AD brains compared with the age-/sex-matched controls detected by Q-PCR (n=7 each group), and the positive correlations with the increased K49-acetylated β-catenin (see Fig. 1I, J) analyzed by Pearson analysis.",
    "ncbi_link": "bcl2: 596
survivin: 332
dkk1: 22943"
  },
  {
    "caption": "D, Western blotting of HSP70, tsg 101, CD81, CD63, and CD9 in EVs, whole blood, and blood clot derived from suckling mice infected with DMEM or NoVΔB2. Staining of β-actin was used as a loading control.",
    "ncbi_link": "B2: 962118"
  },
  {
    "caption": "Immunoblot of lysates prepared from the indicated SAMHD1-proficient (+/+), deficient (-/-) and rescue (WT, H233A) cell line pairs with the indicated antibodies. Representative of 2 independent experiments.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Proliferation inhibition analysis of ara-C and RNRi combination treatment in SAMHD1+/+ or -/- THP-1 cells. Error bars indicate s.e.m. of two (HU and dF-dC) or three (3-AP) independent experiments, each performed in duplicate.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Ara-C EC50 values plotted as a function of RNRi concentration in SAMHD1+/+, -/- and rescue (WT, H233A) THP-1 cell line pairs. EC50 values in the absence of RNRi are indicated by the black and red dotted line. Error bars indicate s.e.m. of two (HU and dF-dC) or three (3-AP) independent experiments, each performed in duplicate.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Drug synergy plots for ara-C and the indicated RNRi in SAMHD1+/+, -/- and rescue (WT, H233A) cell line pairs. Each data point indicates an average delta score from a single dose-response matrix experiment performed in duplicate. Zero, >0, or <0 corresponds to additive, synergy, or antagonism, respectively, whilst >5 indicates strong synergy. The horizontal line and the error bars indicate the mean and s.d., respectively, statistical significance was determined using a two-tailed unpaired t-test: ns, not significant, P ≥ 0.05; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Immunoblot analysis of lysates prepared from SAMHD1+/+ or -/- THP-1 cells treated for 24 h with ara-C and HU, as indicated. Representative of 3 independent experiments.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ or -/- THP-1 cell clones (day 0) and treated with ara-C and/or HU as indicated (day 6). n = 6 per treatment group.",
    "ncbi_link": "luciferase: 
SAMHD1: 25939"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ or -/- HL-60/iva cell clones (day 0) and treated with ara-C and/or HU as indicated (day 6). n = 6 per treatment group.",
    "ncbi_link": "luciferase: 
SAMHD1: 25939"
  },
  {
    "caption": "Kaplan-Meier analysis of NOD/SCID mice injected i.v. with luciferase-expressing SAMHD1+/+ THP-1 cell clone (day 0) and treated with ara-C and/or dF-dC as indicated (day 6). n = 7 per treatment group.",
    "ncbi_link": "luciferase: 
SAMHD1: 25939"
  },
  {
    "caption": "Kaplan-Meier analysis of CD45.2 C57BL/6J mice injected i.v. with murine MLL-AF9-transformed AML blasts (day 0) and treated with ara-C and/or HU days 20-24. n = 5 per treatment group, except for vehicle (n = 4).",
    "ncbi_link": "MLL-AF9: 214162"
  },
  {
    "caption": "Intracellular dNTP measurements using a primer-extension assay in SAMHD1+/+ THP-1 cells treated for 4 or 24 h with either 50 µM HU (middle panel) or 2.5 nM 3-AP (right panel), ratios of dCTP-to-dATP were calculated. Bars indicate mean values of three independent experiments, error bars indicate s.e.m. Statistical analyses were done using unpaired two-tailed t-tests: **, P < 0.01.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Intracellular ara-CTP (upper panel) and dCTP:dATP ratio (lower panel) in the indicated cell lines following the indicated treatment determined using HPLC-MS/MS. SAMHD1-/- THP-1 cells were treated with 500 nM ara-C and SAMHD1+/+ THP-1 cells were treated with either solvent, 500 nM ara-C or a combination of 500 nM ara-C and an RNRi (HU, 50 µM; dF-dC, 10 nM; 3-AP, 150 nM) for 24 h prior. Values relative to mean ara-CTP amounts in ara-C treated SAMHD1+/+ THP-1 cells shown (indicated by dashed line). Circles, columns and error bars correspond to individual values, means and s.e.m. of at least three experiments performed independently.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "Quantificaiton of dCK phosphorylation at serine-74 (S74) with respect to total dCK in SAMHD1+/+ THP-1 cells treated with either solvent, 500 nM ara-C or a combination of 500 nM ara-C and an RNRi (HU, 50 µM; dF-dC, 10 nM; 3-AP, 150 nM) for 24 h. Circles and squares, columns and error bars correspond to individual measurements, means and s.e.m. of one representative out of two independent experiments performed in triplicates.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "(A, B) Knockdown of hnRNPA3 increases poly-GA expression while expressions of EGFP protein levels are not altered upon knockdown of hnRNPs. The control (\"x0\") vector lacks the G4C2 repeats but still contains the 5' flanking region and 3x TAG. ANOVA, Dunnett.",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(C, D) Overexpression of hnRNPA3 suppresses poly-GA expression. n=2 experiments performed in duplicates. ANOVA, Tukey.",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(E) Increased repeat RNA upon hnRNPA3 knockdown. EGFP RNA levels are only slightly increased as compared to levels of the repeat RNA. n=2 experiments performed in duplicates. ANOVA, Dunnett.",
    "ncbi_link": "EGFP: 
hnRNPA3: 220988"
  },
  {
    "caption": "(F, G) Knockdown of hnRNPA3 increases RNA foci. n=3 replicates; two tailed paired t-test, Scale bar=20 μm. All graphs are shown as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(A-C) Rescue of repression of poly-GA and repeat RNA by wild type (wt) hnRNPA3 and hnRNPA2 but not by the RNA binding mutant hnRNPA3DxD. (B) n=3 experiments performed in duplicates; (C) n= 2 experiments performed in duplicates. ANOVA, Tukey.",
    "ncbi_link": "hnRNPA2: 3181
hnRNPA3: 220988"
  },
  {
    "caption": "(D-F) Rescue of repression of poly-GA and repeat RNA by hnRNPA3WT but not the M9-NLS deletion mutant. (E) n=3 experiments performed in duplicates; (F) n=4 experiments performed in duplicates. ANOVA, Tukey. All Graphs are shown as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001 (See also Figure EV1).",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(C) Knockdown of hnRNPA3 increases repeat RNA expression. n=2 experiments performed in duplicates. ANOVA, Dunnett.",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(F) Expression of all the three DPRs is increased upon knockdown of hnRNPA3. Signals from knockdown with siRNA#8 were normalized to 1. n=3 experiments, ANOVA, Dunnett.",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "(G) Co-expression of two/three different DPRs in single cells is increased upon hnRNPA3 knockdown. n=3 replicates, ANOVA, Dunnett. All graphs are shown as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001. Scale bars=20μm. (see also Figure EV2 and EV3).",
    "ncbi_link": "hnRNPA3: 220988"
  },
  {
    "caption": "Rathippocampal neurons at DIV3 were transduced with lentivirus coexpressing either hnRNPA3 targeting shRNA (shA3) or a control shRNA (shCtrl) and tag RFP. Three days after transduction (DIV3+3), neurons were transfected with (G4C2)80HIGH(+0) and analyzed at (DIV3+7). (A) Neurons were fixed, immunostained and imaged by confocal microscopy. Double immunofluorescence for poly-GA aggregates (green) and tag RFP (red). Nuclei were labeled with DAPI. Scale bar represent 20 μm.",
    "ncbi_link": "hnRNPA3: 362152"
  },
  {
    "caption": "Rat hippocampal neurons at DIV3 were transduced with lentivirus coexpressing either hnRNPA3 targeting shRNA (shA3) or a control shRNA (shCtrl) and tag RFP. Three days after transduction (DIV3+3), neurons were transfected with (G4C2)80HIGH(+0) and analyzed at (DIV3+7). (B) Efficient knockdown of endogenous rat hnRNPA3 with its targeting shRNA.",
    "ncbi_link": "hnRNPA3: 362152"
  },
  {
    "caption": "Rat hippocampal neurons at DIV3 were transduced with lentivirus coexpressing either hnRNPA3 targeting shRNA (shA3) or a control shRNA (shCtrl) and tag RFP. Three days after transduction (DIV3+3), neurons were transfected with (G4C2)80HIGH(+0) and analyzed at (DIV3+7). (C) Poly-GA aggregates were detected in a filter trap assay using an anti-Flag antibody. (D) The amounts of poly-GA aggregates were quantified and are presented as the fold change of signals from neurons treated with the control shRNA or the repeat construct. Means ± SD of three independent experiments are shown. * p<0.05 by a Student's t-test. n= 3 replicates.",
    "ncbi_link": "hnRNPA3: 362152"
  },
  {
    "caption": "(B) Knockdown of hnRNPA3 with two independent siRNA results in selective depletion of hnRNPA3 in fibroblasts from 3 C9orf72 repeat carriers. Actin was used as a loading control.",
    "ncbi_link": "C9orf72: 203228
hnRNPA3: 220988"
  },
  {
    "caption": "(C) Knockdown of hnRNPA3 increases RNA foci in cells derived from C9orf72 carriers. No G4C2 repeat RNA foci are detected in fibroblast without C9orf72 repeat expansions (WT). Nucleoli were stained with anti nucleolin antibodies (green) and nuclei were stained with DAPI (blue). (D) Quantification of the relative frequency of RNA foci positive cell (RNA foci positivity) (fold change). n=3 experiments for each case. (E) Quantification of the number of RNA foci per RNA foci-positive cell (fold change). n=3 experiments for each case. (D, E) The average foci number of non-treated (N/T) fibroblast was normalized to 1 in each case. Bars indicate mean. Individual points indicate mean values obtained from a single experiment (49-214 cells were counted in single experiment). Error bars indicate 95%CI, ANOVA, Tukey-Kramer HSD, *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "C9orf72: 203228
hnRNPA3: 220988"
  },
  {
    "caption": "(F) Representative presentation of increased RNA foci in C9orf72 carriers upon lentiviral-mediated hnRNPA3 knockdown. (G) Quantification of the number of RNA foci (fold change). 3 cases were analyzed. Single points indicate an average obtained from 29-30 cells per case. Color code labels values obtained in fibroblasts derived from the three individual patients. Two-tailed t-test. Mean ± SEM. Scale bar= 10 μm.",
    "ncbi_link": "C9orf72: 203228
hnRNPA3: 220988"
  },
  {
    "caption": "(A) Double immunofluorescence staining with anti-GA (green) and anti-hnRNPA3 (red) antibodies of the granular layer of the dentate gyrus of a control case and three C9orf72 mutation cases. In C9 mutation cases with low nuclear hnRNPA3 expression (#8 & #1) more poly-GA aggregates were observed as in cases with high nuclear hnRNPA3 (#7). Inserts show examples of co-localization of poly-GA and hnRNPA3 aggregates.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(B) Granular layer neurons of a C9orf72 mutation case with (white arrows) or without (orange arrows) nuclear clearance of hnRNPA3. (C) poly-GA aggregates are more frequent in C9orf72 mutation cases with lower nuclear hnRNPA3 levels than in those cases with higher nuclear hnRNPA3 levels (divided by median of nuclear hnRNPA3 intensities in 34 C9orf72 mutation cases into two subgroups). Bar graph indicates mean value. Error bars indicate 95% CI. Single points indicate mean from three micrographs per case. Note that the difference in GA positivity between both groups remains significant (p = 0.0086) after removal of the highest outlier in the low nuclear A3 group. Two-tailed t-test. Scale bar = 10 μm.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(B) Equal amounts of synaptoneurosomal samples isolated from mouse brains (Fmr1 KO and wild-type littermates) were permeabilized by saponin and assayed on MitoPlates for 2 hours. Results are presented as the average rate/min/µg of protein, +/- SEM (n=3 per genotype; two-way ANOVA, post-hoc Sidak's multiple comparisons test; *** p< 0.0001).",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "(C) Mitochondrial O2 consumption rates in SN were measured by high-resolution respirometry in the presence of following respiratory substrates: malate, pyruvate, and glutamate for Complexes I-IV, succinate for Complexes II-IV, glycerol 3-phosphate for mGpDH-IV and ascorbate and TMPD for complex IV, and normalized to protein content. Fmr1 KO mitochondria show elevated levels of respiration in the presence of succinate as well as ascorbate and TMPD (*p=0.0483 and *p=0.0360 respectively, n=9 per genotype, paired two-tailed t-test). Data are presented as a box-and-whiskers graph (the box extends from 25th to 75th percentiles, central horizontal line is plotted at the median, whiskers show 5th - 95th percentile).",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "(D) Ultrastructure of Fmr1 KO brain sections revealed important differences in mitochondria morphology when compared to wild-types. Mitochondria are indicated by arrows; presynaptic part in blue, postsynaptic part in green. 3 mice per genotype were analyzed. Scale bars, 0.5 µm.",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "(B) At 24h after transfection of HAT or  KLK5 plasmid in sextuplicate, A549 cells were inoculated with H1N1/pdm at MOI of 0.25. The infected cells were incubated with recombinant wtSPINK6 or mutSPINK6 protein in triplicate for 24h. Culture media in each well were stored in two aliquots, one was applied to viral titration with conventional plaque assay  (black bars), the other was pre-treated with  TPCK-trypsin for 1 hour prior to plaque assay  (grey bars). Data represent the mean and SD of the triplicated wells in a representative experiment performed 3 times. *, P<0.05; **, P<0.01; ***, P<0.001. Student's t test.",
    "ncbi_link": "HAT: 8520
KLK5: 25818"
  },
  {
    "caption": "(B) At 24h after inoculation of H1N1/pdm or mock inoculation in triplicate, 2D  human airway  organoids were harvested to detect mRNA expression levels of the indicated genes normalized with GAPDH. Data represent the mean and SD of a representative experiment performed three times. Data information: *, P<0.05; **, P<0.01; ***, P<0.001. Student's t test.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(A) The association  SNP rs1432689  genotypes are correlated to differential SPINK6  mRNA expression in over 1000 human lung tissues from three centers. The box denotes interquartile range; the thick line and diamond within the box are the median and mean respectively; whiskers are the minimum and maximum and open dots are outliers. Linear regression was used for eQTL data analysis. Data of three cohorts were applied to meta-analysis and resulted in the P-value of the association  SNP.",
    "ncbi_link": "SPINK6: 404203"
  },
  {
    "caption": "(B)   rs1432689 genotypes are correlated to SPINK6 expression in human lung  tissues and  esophagus mucosa from GTEx database. Sample sizes for each genotype are shown in the x-axis. The y-axis shows the normalized expression of SPINK6  (Norm. expression) in the indicated trusses. Median and interquartile range are represented by a white line and dark box respectively. Data distribution is colored with light blue; a wider section of the violin plot indicates the data on the section have a higher frequency. Linear regression was used for data analysis.",
    "ncbi_link": "SPINK6: 404203"
  },
  {
    "caption": "A) and B) Representative images of stress granule proficient (siControl) and deficient (siG3BP1/2) MelJuSo cells expressing the nuclear UPS reporter NLS-GFP-CL1 (A) and the cytoplasmic UPS reporter NES-GFP-CL1 (B). The cells were left untreated (- HS), exposed to 43°C for 30 minutes (HS), or exposed to 43°C for 30 minutes and followed by 4 hours recovery (HS + 4h Rec.). Nucleolar accumulation of NLS-GFP-CL1 during the recovery is indicated by arrows in A). C) and D) Quantifications of the mean cellular GFP fluorescence intensities of A) and B) normalized to untreated control cells (siControl - HS). The frequency and distribution of the relative fluorescence intensities per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits. (n=3 independent experiments, >1000 cells analyzed per condition, Kruskal-Wallis test, ** P<0.01, ns: not significant).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "E) Representative confocal images of immunofluorescent staining of the nucleolar marker nucleolin and the nuclear UPS reporter NLS-GFP-CL1 in control (siControl, left panel) and G3BP1/2-depleted (siGRBP1/2, right panel) MelJuSo cells exposed to a 30 min 43°C heat shock, followed by 4 hours at 37°C (Recovery). Nucleolar accumulation of NLS-GFP-CL1 is indicated by arrows. F) Quantification of the nucleolus/nucleoplasm ratios of NLS-GFP-CL1 intensities in images of experiment shown in E). The frequency and distribution of the ratio per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits. (n=3 independent experiments, 100 cells analyzed per condition, Kruskal-Wallis test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146
GRBP1: 2633"
  },
  {
    "caption": "A) Representative confocal images of immunofluorescent staining of the stress granule marker TIA1 and puromycin-labelled proteins in parental and G3BP1/2 knock-out U2OS cells. Cells were subjected to 43°C heat shock. B) Quantification of the nucleus/cytoplasm ratios of puromycin intensities in images from A). The frequency and distribution of the ratio per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits (n=3 independent experiments, >50 cells analyzed per condition, Kruskal-Wallis test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "E) Representative confocal images of immunofluorescent staining of the stress granule marker TIA1 and puromycin-labelled proteins in control (siControl) and Hsp70-depleted (siHsp70) U2OS cells. Cells were subjected to 43°C heat shock F) Quantification of the numbers of puromycin positive TIA dots per cell in images from E). The numbers of positive foci per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits (n=3 independent experiments, >50 cells analyzed per condition, Kruskal-Wallis test, ** P<0.01).",
    "ncbi_link": "Hsp70: 3303"
  },
  {
    "caption": "G) Representative confocal images of immunofluorescent staining of the nucleolar marker nucleolin and puromycin-labelled proteins in control (siControl) and Hsp70-depleted (siHsp70) G3BP1/2 knock-out U2OS cells. Cells were subjected to 43°C heat shock. H) Quantification of the nucleolus/nucleoplasm ratio of puromycin intensities in images from G). The frequency and distribution of the ratio per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits (n=3 independent experiments, >50 cells analyzed per condition, Mann-Whitney test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146
Hsp70: 3303"
  },
  {
    "caption": "B) Representative confocal images of immunofluorescent staining of HSF1 in parental and G3BP1/2 knock-out U2OS cells directly after heat shock (+ HS) and 2 hours after 2 hours recovery (HS + 2h Recovery). C) Quantification of the number of HSF1 foci per cell in images from B), shown as box plot with median and 5-95 percentiles (n=3 independent experiments, >300 cells analyzed per condition, Kruskal-Wallis test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "D) Western blot analysis of parental and G3BP1/2 knock-out U2OS cells that were left untreated (- HS), heat shocked (HS), and followed for 1, 2, and 4 hours after heat shock (Rec). The blots were probed with antibodies against HSF1 and GAPDH (* indicated phosphorylated HSF1, and ** indicates unphosphorylated HSF1).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "A) Representative confocal images of immunofluorescent staining of the nucleolar marker nucleolin and SUMO2/3 in parental and G3BP1/2 knock-out U2OS cells. Cells were subjected to a heat shock followed by 2 hours recovery. B) Quantification of the nucleolus/nucleoplasm ratio of SUMO2/3 intensities in images from A). The frequency and distribution of the ratio per cell are shown as violin plots. The solid lines in each distribution represent the median, and dash lines represent the upper and lower interquartile range limits (n=3 independent experiments, >50 cells analyzed per condition, Mann-Whitney test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "C) Representative confocal images of immunofluorescent staining of PML bodies (PML) and SUMO2/3 in parental and G3BP1/2 knock-out U2OS cells. Cells were heat shocked followed by 2 hours recovery. Arrows indicate dots positive for PML and SUMO2/3 staining. D) Quantification of SUMO2/3 positive PML puncta in images from C). Data represent the mean ± SD (n=3 independent experiments, >50 cells analyzed per condition, Mann-Whitney test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "E) Analysis of SUMO2/3 conjugates in parental and G3BP1/2 knock-out U2OS cells that were left untreated (- HS), exposed to a heat shock (+ HS), and followed for 2 hours (2h Rec.) with or without 100 nM proteasome inhibitor epoxomicin (EPX).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "A) Representative confocal images of immunofluorescent staining of SUMO2/3 and TDP43 in parental and G3BP1/2 knock-out U2OS cells. Cells were exposed to a heat shocked followed by 2 hours recovery. Arrows indicate dots positive for TDP-43 and SUMO2/3 staining. B) Quantification of the percentage of SUMO2/3 positive TDP43 puncta in images from experiment shown in A)..Data represent the mean ± SD (n=3 independent experiments, >50 cells analyzed per condition, Mann-Whitney test, ** P<0.01).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "D) Analysis of detergent SDS and NP40 soluble fractions of TDP43 in parental and G3BP1/2 knock-out U2OS cells that were left untreated (-HS), exposed to 43°C (+HS) followed by 2 hours recovery (2h Rec.) in absence or presence of 100 nM proteasome inhibitor epoxomicin (EPX). E) Quantification of the TDP43 band densities in the SDS-soluble fraction. Data represent the mean ± SD (n=3 independent experiments, Student's unpaired t-test, * P<0.05).",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "A) Analysis of SUMO2/3 conjugates in control (siControl) or RNF4-depleted (siRNF4) G3BP1/2 knock-out U2OS cells. Cells were left untreated (-HS), exposed to 43°C (+ HS), followed by 2 hours recovery (HS + 2h Rec.) in the absence or presence of 100 nM proteasome inhibitor epoxomicin (EPX). B) Quantification of the total SUMO2/3 band densities. Data represent the mean ± SD (n=3 independent experiments, *P<0.05).",
    "ncbi_link": "G3BP1: 10146
RNF4: 6047"
  },
  {
    "caption": "E) Representative confocal images of control (siControl), RNF4-depleted (siRNF4), G3BP1/2-depleted (siG3BP1/2) and G3BP1/2+RNF4-depleted (siG3BP1/2 + siRNF4) MelJuSo cells expressing the nuclear UPS reporter NLS-GFP-CL1. Cells were exposed to heat shock followed by 4 hours recovery in the absence or presence of the proteasome inhibitor epoxomicin (EPX). The nucleolar marker nucleolin was stained by immunofluorescence.",
    "ncbi_link": "G3BP1: 10146
RNF4: 6047"
  },
  {
    "caption": "A) Representative confocal images of immunofluorescent staining of FLAG-tagged ubiquitin (FLAG-Ub) and mutant ataxin1 (ATX1) in parental and G3BP1/2 knock-out U2OS cells. Cells were subjected to heat shock followed by 4 hours recovery. B) Frequency distribution of ataxin-1 inclusions per cell from three independent experiments.",
    "ncbi_link": "G3BP1: 10146"
  },
  {
    "caption": "BNGE of whole-body zebrafish digitonin-solubilized mitochondria of scaf1Δ1/Δ1 (-/-) and its respective scaf1+/+ counterpart. Immunodetection of the indicated proteins",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "BNGE of whole-body zebrafish digitonin-solubilized mitochondria of scaf1Δ1/Δ1 (-/-) and its respective scaf1+/+ counterpart. (G) in-gel activity of CI and (H) CIV (representative gel from two technical and three biological replicates).",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "I, 2D BNGE/SDS electrophoresis: 1st dimension with digitonin (Dig) and 2nd dimension with SDS, followed by immunoblotting with the indicated antibodies to identify the proteins detected by the commercial anti-SCAF1 antibody. Asterisks indicate missing bands in scaf1Δ1/Δ1.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "A, Quantitative data-independent scanning (DiS) mass spectrometry protein profiles for CI, CIII and CIV. Vertical numbers indicate the BNGE gel slices. Left and right profiles correspond to scaf1+/+ and scaf1Δ1/Δ1 animals, respectively. Red heatmap corresponds to the E-score from two proteotypic Scaf1-derived tryptic peptides spanning sequences ascribed to the CIII interacting site (in green) and to the CIV interacting site (in yellow). Thick blue line, marked with an asterisk, indicates the putative proteolytic site in Scaf1.",
    "ncbi_link": "scaf1: 553490
Scaf1: 553490"
  },
  {
    "caption": "A, B, Representative images from scaf1+/+ and scaf1-/- (A) female and (B) male adult zebrafish.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "c-f, Size of scaf1Δ1/ Δ1 and scaf1Δ2/ Δ2 (scaf1-/-) fish in comparison with their respective scaf1+/+ lines, (C) length and (E) weight of females (Δ1 +/+ n=10, Δ1 -/- n=12, Δ2 +/+ n=24, Δ2 -/- n=18); (D) length and (F) weight of males (Δ1 +/+ n=16, Δ1 -/- n=13, Δ2 +/+ n=13, Δ2 -/- n=23).",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "L-N, Effect of Scaf1 loss of function on female fertility. (L) Number of eggs per clutch (Δ1 +/+ n=12, Δ1 -/- n=13, Δ2 +/+ n=13, Δ2 -/- n=10). (M) Quantification of mature ovary follicles per ovary section (average of three sections/biological replicate) (Δ1 n=5, Δ2 n=8; same number of animals for homozygous scaf1+/+ and scaf1-/-). (N) Representative images of H&E-stained ovaries. Dotted lines delineate adipose tissue.",
    "ncbi_link": "scaf1: 553490
Scaf1: 553490"
  },
  {
    "caption": "Transmission electron microscopy image of cardiac muscle from scaf1Δ1/Δ1 (n=3) and scaf1+/+ fish (n=3). (A) Representative images showing mitochondria.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "Transmission electron microscopy image of cardiac muscle from scaf1Δ1/Δ1 (n=3) and scaf1+/+ fish (n=3). (B) Mitochondria size (100-150 mitochondria per biological sample). (C) Cristae lumen width (average of three cristae per mitochondria, 20 mitochondria per biological sample). Different biological replicates are represented with different color tones.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "A, Representative images of scaf1-/- and scaf1+/+ fish fed with the indicated diets.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "D-F, Adipose tissue measurements on hematoxylin-eosin (H&E)-stained adult zebrafish sagittal sections. (D) Adipose tissue area per total section area (average of three sections/biological replicate) and (E) adipocyte size (average of 20-30 adipocytes of ventral adipose tissue per biological replicate) (Δ1 +/+ n=3, Δ2 n=8). scaf1Δ1 and scaf1Δ2 are represented with circles and squares, respectively.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "A, B, Representative images of scaf1-/- and scaf1+/+ females (A) and males (B) fed with the indicated diets.",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "A, Immunoblot of the indicated proteins of BNGE from female scaf1+/+ and scaf1-/- whole zebrafish mitochondria for the indicated diet (representative of n=2).",
    "ncbi_link": "scaf1: 553490"
  },
  {
    "caption": "RNAseq data from scaf1+/+ and scaf1-/- skeletal muscle for the indicated diet (standard diet scaf1+/+ and scaf1-/- n=4, double diet scaf1+/+ n=3, scaf1-/- n=4). (C-F) Volcano plots of differentially expressed genes (DEGs). (C) Comparison between scaf1-/- and scaf1+/+ zebrafish in standard diet. (D) Comparison between scaf1-/- and scaf1+/+ zebrafish in double diet. (E) Comparison of scaf1+/+ zebrafish in double diet and standard diet. (F) Comparison of scaf1-/- zebrafish in double diet and standard diet. In blue, significant DEGs (p-adj < 0.05, log2FC > |1|), in grey not significant DEGs, red circles represent non-significant differentially regulated OXPHOS genes, green circles represent significant differentially regulated OXPHOS genes, purple scaf1 (cox7a2l).",
    "ncbi_link": "cox7a2l: 335751
scaf1: 553490
scaf1button type=\"button\" class=\"btn btn-success btn-xs\" ng-click=\"confirmPretag(true,'p: 553490"
  },
  {
    "caption": "B. Western blots of MDI protein in wild type (wt) and mdi1 flies, showing that mdi1 is a protein-null mutation. Tubulin was used as loading control.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "A-C. mtDNA replication in wt (A) and mdi1 ovarioles (B, C) as illustrated by EdU incorporation. Arrows point to mitochondrial DNA, arrowheads to nuclei. In wt ovaries (A), mtDNA replication starts at germarium stage 2B and lasts into egg-chamber stage 2 (S2). In most mdi1 ovarioles (B), mtDNA replication is undetectable at these stages, whereas in some (C) it appears delayed until germarium stage 3. Bars, 10 m.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "D. Hatching rates and mtDNA content of eggs laid by females of different mutant genotypes relative to eggs laid by wt controls. Each data point represents the mean of 3 independent replicates. Expression of mdi or hAKAP1 in mdi1 significantly restored the mtDNA level and hatching rate. N= 3 x >100 eggs / genotype for hatching rate. The relative mtDNA level was determined as the average of 3 biological repeats. P values of comparing mdi1; nos> mdi to mdi1: hatching rate, P= 1.1995E-05; mtDNA, P= 0.0078. P values of comparing mdi1; nos> hAKAP1 to mdi1: hatching rate, P= 1.6998E-05; mtDNA level, P= 0.0009.",
    "ncbi_link": "AKAP1: 8165
nos: 42297
mdi: 31459"
  },
  {
    "caption": "B. Representative images of S2 cells expressing GFP fusions (green) of the MDI proteins diagramed in (A). Staining with MitoTracker Red (red) to label mitochondria shows an overlapping signal (yellow), indicating proper localization to mitochondria for all fusion proteins except MDIΔMTS.",
    "ncbi_link": "MDI: 31459"
  },
  {
    "caption": "D. Western blots of MDI protein in wt and mdi knockout (mdi-ko) cells confirming the mdi-ko cells completely lacked MDI protein. Actin was used as loading control.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "E. Representative images of wt or mdi-ko cells expressing a Larp-GFP fusion protein and stained with MitoTracker Red to label mitochondria. The majority of Larp localized to mitochondria in wt cells (overlapping red and green signal), but diffused into the cytoplasm of mdi-ko cells.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "F. Representative images of mdi-ko cells co-expressing Larp-GFP with MDI or the deletion mutants diagramed in (A) fused to the mCherry. Of the 4 MDI deletions that localized to mitochondria, 2 (MDIΔR and MDIΔTudor) did not allow Larp-GFP to localize to mitochondria. The localization of Larp in mdi1 flies expressing MDI or MDI deletion mutants, and the hatching rate and mtDNA level in their eggs were determined. The result was summarized in (A).",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "B. mtDNA replication, as illustrated by EdU incorporation, in wt and larp mutant (larp) ovarioles. mtDNA replication is dramatically reduced in the larp ovariole. Arrows: mtDNA; arrowheads: nuclei.",
    "ncbi_link": "larp: 53567"
  },
  {
    "caption": "C. wt and mdi1 egg chambers stained for Larp (green) and ATP-S (red) to reveal mitochondria. Larp closely associates with mitochondria in wt egg chambers. Mitochondria in mdi1 flies are clumped together, and completely lack Larp staining. Bars in (B) & (C): 10 m.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "A. Nascent protein synthesis revealed by HpG incorporation (green) in wt and mdi1 egg chambers. Arrowheads point to the HpG signal on the ER in the perinuclear region and cell periphery. Arrows point to HpG signal associated with mitochondria. Mitochondria are marked by a Tom20-mCherry (red) created by inserting mCherry at the endogenous Tom20 locus.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "B. ER location is unaltered in mdi1 egg chambers. An ER marker (ER-GFP) was expressed in wt and mdi1 egg chambers that were co-stained with ATP-S to mark mitochondria. ER localizes to the perinuclear region, cytoplasm and cell periphery in both wt and mdi1 egg chambers.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary. A. Nascent protein synthesis was monitored by AHA incorporation, and detected by anti-biotin antibody. Tom20 served as a loading control. Note that the synthesis of nuclear-encoded mitochondrial proteins was decreased in the mdi1 background and was restored by overexpressing Tom20-Larp (mdi1/TL).",
    "ncbi_link": "Larp: 53567
mdi: 31459
Tom20: 40189"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary.B. Western blots of mitochondrial proteins in ovarioles of wt, mdi1 and mdi1 flies expressing Tom20-Larp (mdi1/TL) fusion protein. Note that levels of Tamas, TFAM, mRpL19 and COX4 were reduced in mdi1 flies, but restored in mdi1/TL flies.",
    "ncbi_link": "Larp: 53567
mdi: 31459
Tom20: 40189"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary. C. Nascent protein synthesis of Tamas and TFAM was decreased in mdi1 ovary, whereas mtSSB was not affected. Tfamgfp, Tamasgfp and mtSSBgfp were expressed in wt or mdi1 background. Nascent proteins were labeled by AHA incorporation and then the GFP-tagged protein was immunopurified with a GFP antibody and the nascent protein synthesis was detected by anti-biotin antibody.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary. D. Representative profile of 254 nm absorbance of wt, mdi1 and mdi1/TL ovary extracts.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary. E. Polysome mRNA profiling for tamas, tfam, mtSSB, cox4 and mRPL19 in wt, mdi1 and mdi1/TL ovary. The percentage of mRNA for each gene in non-polysomal fractions (N.P, including ribosomal subunits and monosome-associated) and polysomal fractions (poly) was calculated and plotted. The fractions of tamas, tfam, cox4 and mRPL19 mRNAs in the polysomal fractions were significantly decreased in mdi1 compared to wt, but were restored in mdi1/TL flies. N=4 for all samples. P values of comparing wt to mdi1: tamas, P= 0.0055; tfam, P= 0.001; cox4, P=0.0066; mRPL19, P=0.0097. P values of comparing mdi1/TL to mdi1: tamas, P= 0.0206; tfam, P= 0.0346; cox4, P=0.0036; mRPL19, P=0.0016.",
    "ncbi_link": "cox4: 35279
mRPL19: 41028
mtSSB: 41968
mdi: 31459
tamas: 34792
tfam: 42433"
  },
  {
    "caption": "Detection of nascent protein synthesis in the mitochondrial fraction of the ovary. F. The nascent protein synthesis of COX4 and mRPL19 were decreased in mdi1 ovary and were restored mdi1/TL flies. The proteins were immunopurified with antibodies against the endogenous proteins.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "A. Mitochondrial localization of a Tom20-LarpGFP (Tom20-Larp) fusion protein in an mdi1 egg chamber stained with ATP-S to reveal mitochondria. Bars, 20 m.",
    "ncbi_link": "mdi: 31459"
  },
  {
    "caption": "B. Hatching rates and mtDNA contents of eggs produced by flies with different genotypes relative to wt control; each data point represents the mean of 3 independent replicates. Bars, std. Expression of Tom20-Larp in mdi1 (mdi1;Tom20-Larp) significantly restored the mtDNA level and hatching rate. N= 3 x >100 eggs / genotype for hatching rate. The relative mtDNA level was the average of 3 biological repeats. P values of comparing mdi1;Tom20-Larp to mdi1: for mtDNA level, P=0.0209; for hatching rate, P=3.4758E-05.",
    "ncbi_link": "Larp: 53567
mdi: 31459
Tom20: 40189"
  },
  {
    "caption": "(C) STIM1 and STIM2 mRNA expression in PBMC of P1, P2, mother and a healthy donor (HD) that were left unstimulated or stimulated with anti-CD3/CD28 for 24 hours. mRNA levels of STIM1/2 normalized to 18S. Graph shows the mean ± SEM of duplicates from one experiment.",
    "ncbi_link": "18S: 
STIM1: 6786
STIM2: 57620"
  },
  {
    "caption": "GFP-ORAI1 expressing HEK293 cells were transfected with mCherry-STIM1 (WT or L374P) and left unstimulated or stimulated with 1 μM TG in Ca2+-free Ringer's solution. (D,E) Representative TIRF microscopy images from one of two repeat experiments. Scale bars, 10 μm.",
    "ncbi_link": "GFP: 
mCherry: 
ORAI1: 84876
STIM1: 6786"
  },
  {
    "caption": "GFP-ORAI1 expressing HEK293 cells were transfected with mCherry-STIM1 (WT or L374P) and left unstimulated or stimulated with 1 μM TG in Ca2+-free Ringer's solution. (F) Percentages of WT or mutant mCherry-STIM1 present at the plasma membrane (i.e. visible in the TIRFM evanescent field) before TG stimulation. Data are the mean ± SEM calculated from 550 (WT) and 830 (L374P) cells from two independent experiments. (G) Change of mCherry-STIM1 (WT or L374P mutant) fluorescence [F(t)/F(0)] in the TIRFM evanescence field. Fluorescence normalized to values at the time of TG addition in Ca2+-free Ringer's buffer at 0 sec. Traces show mean ± SEM of 40-50 cells from two independent experiments. (H) Colocalization of mCherry-STIM1 (WT or L374P mutant) and GFP-ORAI1 from the time of TG addition at 0 sec. Colocalization measured using the Pearson's coefficient for GFP and mCherry.",
    "ncbi_link": "GFP: 
mCherry: 
ORAI1: 84876
STIM1: 6786"
  },
  {
    "caption": "A) Severe onychomycosis in P2 (STIM1 p.L374P).",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "Sublingual infection of WT, Stim1fl/flVav-iCre and Stim1fl/flStim2fl/flVav-iCre mice with 2x107 CFU of C. albicans. (A) Body weight (BW) measured for 7 days and normalized to BW at day 0 of infection. Data are mean ± SEM measured from 4 repeat experiments and 13 WT, 7 Stim1fl/flVav-iCre, 8 Stim1fl/flStim2fl/flVav-iCre mice.",
    "ncbi_link": "iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "Sublingual infection of WT, Stim1fl/flVav-iCre and Stim1fl/flStim2fl/flVav-iCre mice with 2x107 CFU of C. albicans. (B) Quantification of CFU of C. albicans per gram tongue tissue of the indicated mice at day 7 p.i. Data are mean ± SEM from 4 repeat experiments and 12 WT, 7 Stim1fl/flVav-iCre, 8 Stim1fl/flStim2fl/flVav-iCre mice.",
    "ncbi_link": "iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "Sublingual infection of WT, Stim1fl/flVav-iCre and Stim1fl/flStim2fl/flVav-iCre mice with 2x107 CFU of C. albicans. (C) Macroscopic images of the C. albicans-infected tongues of mice at day 7 p.i. Arrows and dashes lines indicate C. albicans infiltrated areas.",
    "ncbi_link": "iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "Sublingual infection of WT, Stim1fl/flVav-iCre and Stim1fl/flStim2fl/flVav-iCre mice with 2x107 CFU of C. albicans. (D) Histological images of H&E (left) and PAS (right) stained tongue tissue at day 7 p.i. Clusters of polymorphonuclear (PMN) cells (neutrophils, white arrows) and Candida (black arrows) are indicated.",
    "ncbi_link": "iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "Sublingual infection of WT, Stim1fl/flVav-iCre and Stim1fl/flStim2fl/flVav-iCre mice with 2x107 CFU of C. albicans. (E) Frequencies of Cd11b+Gr1+ neutrophils in the tongues from the indicated mice at day 7 p.i. Bar graphs represent the mean ± SEM from 3 experiments and 9 WT, 7 Stim1fl/flVav-iCre, 8 Stim1fl/flStim2fl/flVav-iCre mice.",
    "ncbi_link": "iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "(F,G) Cytokine production by CD4+ T cells isolated from submandibular lymph nodes of WT, Stim1fl/flVav-iCre, Stim1fl/flStim2fl/flVav-iCre and Stim1fl/flCd4Cre mice 7 days after sublingual infection with 2x107 CFU C. albicans. Representative contour plots of cytokine production (F) and percentages of CD4+ T cells producing TNF-α, IFN-γ, IL-17A, IL-17F and GM-CSF (G). Data are the mean ± SEM from two independent experiments and 9 WT, 7 Stim1fl/flVav-iCre, 8 Stim1fl/flStim2fl/flVav-iCre mice.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
iCre: 2777477
Stim1: 20866
Stim2: 116873
Vav: 22324"
  },
  {
    "caption": "Candicidal function of neutrophils depend on SOCE. (H) Coculture of Cd11b+Gr-1+ neutrophils from WT, Stim1fl/flMx1Cre and Stim1fl/flStim2fl/flMx1Cre mice with C.albicans in vitro for 0, 30, 60 and 90 min (MOI 0.5). Percentages of live C.albicans isolated from neutrophils that were lysed at the indicated time points. Data are the mean ± SEM from 6 mice per genotype and 3 independent repeat experiments.",
    "ncbi_link": "Cre: 2777477
Mx1: 17857
Stim1: 20866
Stim2: 116873"
  },
  {
    "caption": "ROS production of neutrophils depend on SOCE. (I) ROS production by Cd11b+Gr-1+ neutrophils from WT, Stim1fl/flMx1Cre and Stim1fl/flStim2fl/flMx1Cre mice was measured after loading of cells with dihydrorhodamine 123 and stimulation with 10 nM PMA for 30 minutes. Representative histogram plots and bar graphs indicating the percentages of ROS+ neutrophils normalized to WT neutrophils stimulated with PMA.",
    "ncbi_link": "Cre: 2777477
Mx1: 17857
Stim1: 20866
Stim2: 116873"
  },
  {
    "caption": "Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (A) Body weight (BW) change measured for 7 days p.i. relative to BW at the day of infection. Data are mean ± SEM measured from 4 repeat experiments and 13 WT and 7 Stim1fl/flCd4Cre mice.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (B) Quantification of CFU of C. albicans isolated from the tongues of mice at day 7 post-infection (p.i.). Data are mean ± SEM from 4 repeat experiments and 7-13 mice per genotype.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (C) Macroscopic images of the C. albicans-infected tongues of mice at day 7 p.i.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Sublingual C. albicans infection of WT and Stim1fl/flCd4Cre mice as described in Figure 5. (D) Histological images of H&E (left) and PAS-stained (right) tongue tissue at day 7 p.i. Scale bars 100 μm. Arrows point to clusters of polymorphonuclear (PMN) cell (neutrophil) infiltrates.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (E) Kaplan-Meier survival plot showing survival of mice. Data from 5 Stim1fl/fl Cd4Cre mice and 12 WT mice is shown.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (F) Body weight (BW) of mice normalized to BW at the day of infection. Data are the mean ± SEM from 4 independent experiments and 8 WT and 7 Stim1fl/flCd4Cre mice.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (G) Representative macroscopic images of kidneys at day 6 p.i.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (H) CFUs of C. albicans per gram tissue isolated from the liver, the right kidney and the lung of mice at day 6 p.i. Each dot represents one mouse.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (I) Representative histological images of H&E and PAS stained kidneys of mice at day 6 p.i. Magnification 6.4x (left) and 40x (right). White arrows define areas infiltrated with leukocytes (H&E) and C. albicans (PAS).",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (J) Frequencies of CD4+ T cells isolated from the spleens of mice at day 6 p.i. producing the indicated cytokines after restimulation with 20 nM PMA and 1 μM ionomycin for 6 hours and analyzed by flow cytometry.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Systemic C. albicans infection. WT and Stim1fl/fl Cd4Cre mice were injected i.v. with 2x105 CFU C.albicans or PBS as control. (K) Frequencies CD45+Cd11b+Gr-1+ neutrophils in the blood of mice at day 6 post-infection analyzed by flow cytometry. Data in J are the mean ± SEM from 2 independent experiments and 6 WT and 4 Stim1fl/flCd4Cre mice; data in K are the mean ± SEM from one experiment and 2 WT and 3 Stim1fl/flCd4Cre mice.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "RNA-seq analysis of CD4+ T cells isolated from 3 WT and 3 Stim1fl/flCd4Cre mice that were differentiated into pathogenic Th17 cells (pTh17: IL-1β, IL-6, IL-23) and non-pathogenic Th17 cells (npTh17: IL-6, TGFβ1). (B) Volcano plots of DEGs in npTh17 cells (gray dots). Highlighted in red (upregulated in Stim1fl/flCd4Cre) and blue (downregulated in Stim1fl/flCd4Cre) are DEGs that belong to a gene expression signature of npTh17 cells and pTh17 cells defined previously (Gaublomme et al., 2015, Lee et al., 2012).",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "(C) Normalized expression of Th17 cell-associated cytokines and receptors in npTh17 cells derived from WT and Stim1fl/flCd4Cre mice. Bar graphs represent the mean ± SEM from 3 mice per group. Statistical analysis by unpaired Student's t-test with the following significance levels: *p<0.05, ***p<0.001.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "(G) Gene set enrichment analysis (GSEA) of DEGs in WT and STIM1-deficient npTh17 cells. Normalized enrichment score (NES) and p-values are as indicated for the following genesets: Myc targets: "Menssen_myc_targets"; Glycolysis: "Humancyc_mm_glycolysis_i"; Mitochondrial function: "Wong_mitochondria_gene_module"; TCA cycle: "Kegg_mm_citrate_cycle".",
    "ncbi_link": "STIM1: 20866"
  },
  {
    "caption": "(A) Heat map of metabolism-associated DEGs (p (adj.) < 0.10) in npTh17 cells of WT and Stim1fl/flCd4Cre mice determined by RNA-Seq as described in Figure 7. Heatmap shows relative minimum and maximum values per gene (row min/max). Numerical values are relative gene expression. TCA, tricarboxylic acid.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Glucose and mitochondrial metabolism in npTh17 cells from WT (grey or black) and Stim1fl/flCd4Cre (blue)mice differentiated for 3 days in vitro. (B) Glucose uptake by npTh17 cells were loaded with 2-NBDG (+) or not (-) and analyzed by flow cytometry 90 min later. Bar graphs show the delta MFI of 2-NBDG fluorescence normalized to unlabeled cells. Data represent the mean ± SEM from 3 independent experiments.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Glucose and mitochondrial metabolism in npTh17 cells from WT (grey or black) and Stim1fl/flCd4Cre (blue)mice differentiated for 3 days in vitro. (D) Oxygen consumption rate (OCR) of npTh17 cells before and after addition of 1 μM oligomycin, 1.5 μM FCCP and 100 nM rotenone / 1 μM antimycin. Seahorse graphs and bar graphs depicting basal and maximal respiration, coupling efficiency and ATP production represent the mean ± SEM from of 2-3 mice per genotype from one representative out of three independent experiments.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Stim1: 20866"
  },
  {
    "caption": "Expression patterns of Hoxa5 and Hoxc8 mRNAs, as revealed by in situ hybridization, aligned with corresponding sections showing Hoxa5 and Hoxc8 immunostainings in MNs (demarcated with pink/white dashed lines) along the cervical spinal cord (cervical C5 to C7) in mouse embryos at E12.5. Pink scale bar, 50 μm. White and pink dash lines demarcate the postmitotic MN region.",
    "ncbi_link": "Hoxa5: 15402
Hoxc8: 15426"
  },
  {
    "caption": "Hoxa5 expression upon miR-27 knockdown, with exposure to RAhi for 72 h, or with exposure to RAhi for 48 h, and then switching to RAlow plus RAR inhibitor (1 µM) for a further 24 h, or with exposure to RAmed for 72 h.",
    "ncbi_link": "miR-27: 387220"
  },
  {
    "caption": "(C) Immunostaining at cervical spinal cord sections reveals Hoxa5 expansion into the MNs of cervical C6/7 segments of miR-23~27~24 double KO (DKO) mice. miR-23a~27a~24-2+/-;miR-23b~27b~24-1-/- mice were used as a control (ctrl). (E) Conversely, Hoxc8 is shifted into the MNs of cervical C5 segments of both miR-196a2/b DKO and miR-196a1/a2/b triple knockout (TKO) embryos. Age-matched wild type embryos were used as controls. Scale bar represents 50 μm. White dash lines demarcate the postmitotoic MN domain (D, F) Quantifications of Hoxa5on, Hoxc8on, and Hoxa5on Hoxc8on cells in the cervical spinal cord of control and knockout embryos (mean ± SD, N=3 embryos, *p < 0.01, Student's t-tests ).",
    "ncbi_link": "miR-196a1: 387191
miR-196a2: 723958
miR-23: 387216
miR-23a: 387216
miR-23b: 387217"
  },
  {
    "caption": "A, B. Immunoblotting were performed to validate Mettl3 or Mettl14 expression levels in CT26 and B16 cells as indicated. Gapdh served as a loading control.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "Tumor volume was monitored for control and Mettl3 or Mettl14-depleted tumors with treatment as indicated in CT26 colon cancer Data are mean ± s.e.m of the indicated number of mice in each group. n, the numbers of mice. * P < 0.05; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "Tumor volume was monitored for control and Mettl3 or Mettl14-depleted tumors with treatment as indicated in B16 melanoma, respectively. Data are mean ± s.e.m of the indicated number of mice in each group. n, the numbers of mice. * P < 0.05; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "C. Percentage of Granzyme B-expressing CD8+ T cells from control and Mettl3 or Mettl14 deficient CT26 tumors. Each spot represents one mouse. * P < 0.05; * * P < 0.01 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "Mice bearing control and Mettl3 or Mettl14 null tumors were treated with CD8-depleting antibody and PD-1 antibody or PD-1 as indicated. Tumor volume was measured over time points. n, the numbers of mice. * P < 0.05; * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "Mice bearing control and Mettl3 or Mettl14 null tumors were treated with CD8-depleting antibody and PD-1 antibody or PD-1/GVAX as indicated. Tumor volume was measured over time points. n, the numbers of mice. * P < 0.05; * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "A. Volcano plot of differentially expressed genes obtained by DESeq2 analysis in Mettl3 or Mettl14 null tumors compared to control tumors. Significantly upregulated or downregulated genes are plotted in red and blue points, respectively. n.s, non-significant.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "G. m6A enrichment of Stat1 and Irf1 was examined by m6A RIP-qPCR in control, Mettl3, or Mettl14 depleted CT26 tumors as indicated. Ctla4 functioned as a m6A negative control (Wang et al., 2019) Data are mean ± s.d. * * P < 0.01 by Student's t-tests.",
    "ncbi_link": "Ctla4: 12477
Irf1: 16362
Mettl14: 210529
Mettl3: 56335
Stat1: 20846"
  },
  {
    "caption": "I. Tumor growth from CT26 cells with Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1 or Mettl14/Irf1-depleted genes and control under treatment of PD-1 antibody as indicated. n, the numbers of mice. Data are mean ± s.e.m of the indicated number of mice in each group.",
    "ncbi_link": "Irf1: 16362
Mettl14: 210529
Mettl3: 56335
Stat1: 20846"
  },
  {
    "caption": "A. Cellular proliferation analysis of Mettl3 or Mettl14 depleted and control CT26 cells treated with indicated combinations of cytokines for 48h. The mean ± SD of three replicates is shown. * P < 0.05; * * P < 0.01 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "B. BALB/c mice bearing Mettl3 or Mettl14 deficient and control tumors were treated with IFNγ -blocking antibody and PD-1 antibody as indicated. Tumor size was measured over time. n, the numbers of mice. Data are mean ± s.e.m of the indicated number of mice. * P < 0.05; * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Mettl14: 210529
Mettl3: 56335"
  },
  {
    "caption": "D, E. mRNA stability of Stat1 and Irf1 were measured by qRT-PCR in tumor cells treated with IFN-γ and actinomycin D. Mean ± SD of n=3. * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Irf1: 16362
Stat1: 20846"
  },
  {
    "caption": "F. Validation the effect of knock out of Ythdf1-3 using western blotting, Gapdh served as a loading control.",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "G. qPCR analysis of Stat1 and Irf1's expression in the indicated depletion of CT26 cells with/without stimulation of IFNγ. Mean ± SD of n=3. * P < 0.05 by Student's t-tests.",
    "ncbi_link": "Irf1: 16362
Stat1: 20846"
  },
  {
    "caption": "I, J. qPCR analysis of the mRNA stability of Stat1 and Irf1 in the indicated CT26 cells treated with IFNγ and actinomycin D. Mean ± SD of n=3. * P < 0.05; * * P < 0.01; * * * P < 0.001 by Student's t-tests.",
    "ncbi_link": "Irf1: 16362
Stat1: 20846"
  },
  {
    "caption": "Human osteosarcoma U2OS cells (B or neuroglioma H4 cells (D stably expressing GFP-LC3 were treated with a library of chalcones (30 µM) as indicated , or were left untreated for 6 h. The cells were then fixed and GFP-LC3 dots were counted as an indicator for autophagy. Data are means ± SD (* = p < 0.05; ** = p < 0.01;*** = p < 0.001). Representative images are shown in (B,D). Scale bar equals 10 µm. (C,E) Acetylation: U2OS and H4 cells were treated as described above, followed by incubation with specific antibodies to block acetylated tubulin; Thereafter immunofluorescence was conducted with antibodies against acetylated lysine residues and appropriate AlexaFluor conjugated secondary antibodies before the assessment of cytoplasmic fluorescence intensities. Representative images of acetylation are shown in (C,E). Scale bar equals 10 µm.",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "Human osteosarcoma U2OS cells F) or neuroglioma H4 cells H) stably expressing GFP-LC3 were treated with a library of chalcones (30 µM) as indicated or rapamycin (10 µM), or were left untreated for 6 h. The cells were then fixed and GFP-LC3 dots were counted as an indicator for autophagy. Data are means ± SD (* = p < 0.05; ** = p < 0.01;*** = p < 0.001). Viability: U2OS and H4 cells were treated with 30 µM of the indicated chalcones for 24 h and then nuclei were stained with Hoechst 33342 and the number of cells harboring normal nuclei (i.e. non pyknotic, "healthy cells") was determined. All chalcones were hierarchically clustered upon z-scoring the following phenotypes: autophagy (number of GFP-LC3 dots), viability (number of healthy cells) and acetylation (cytoplasmic fluorescence intensity of acetylated lysine residues) in U2OS and H4 cells. Results are reported as a heatmap (G, I).",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "(G,H) U2OS-GFP-LC3 cells were treated with 30 µM 3,4-DC, 10 µM rapamycin, or left untreated for 16 h in the presence or absence of CQ for 4 h. GFP-LC3 dots were measured. Data are means ± SD (*** = p < 0.001 versus untreated; ###=p<0.001 versus CQ).",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "(I,J) U2OS cells stably expressing LC3 fused with tandem fluorescent GFP-RFP proteins (GFP-RFP-LC3) were treated with the indicated raising doses of 3,4-DC or 50 µM chloroquine (CQ) for 16 h. After fixation, GFP-LC3 and RFP-LC3 dots were measured by automated image acquisition and analysis. GFP and RFP double positive LC3 dots indicating autophagosomes (GFP+), and GFP negative but RFP positive LC3 dots indicating autolysosomes (GFP-) were counted in (J). Data are means ± SD (* = p < 0.05;** = p < 0.01;*** = p < 0.001). Representative images are shown in I. Scale bar equals 10 µm.",
    "ncbi_link": "LC3: 81631"
  },
  {
    "caption": "(C, D) H4-GFP-LC3 cells were treated with 30 µM 3,4-DC in the presence or absence of CHX or AMD or with CQ for 16 h as controls, as indicated. GFP-LC3 dots were quantified in (D). Data are means ± SD (* = p < 0.05, ** = p < 0.01 versus untreated control; # = p < 0.05 versus untreated with CQ).",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": ",G) U2OS GFP-LC3 cells were enucleated to obtain cytoplasts, which were further treated with 3,4-DC and torin1. GFP-LC3 dots in cytoplasts were counted as shown in (G). Data are means ± SD (** = p < 0.01). Representative images with cytoplast marked by a white square are shown in (F). Scale bar equals 10 µm.",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "U2OS cells stably expressing GFP-TFEB fusion protein were treated with indicated chalcones at 30 µM for 6 h. GFP intensities in nuclei and cytoplasm were measured and the ratio of GFP intensities in nuclei and cytoplasm were calculated to indicate TFEB translocation to nuclei (A). Data are means ± SD (* = p < 0.05;** = p < 0.01;*** = p < 0.001).",
    "ncbi_link": "GFP: 
TFEB: 7942"
  },
  {
    "caption": "U2OS cells stably expressing GFP-TFEB fusion protein were treated with indicated chalcones at 30 µM for 6 h. Representative images are shown in (B). Scale bar equals 10 µm.",
    "ncbi_link": "GFP: 
TFEB: 7942"
  },
  {
    "caption": "MEF wild type and TSC2 knockout (TSC2 KO) cells were treated with 3,4-DC for 6 h. The cells were fixed and immunofluorescence was performed to detect endogenous TFEB. The ratio of TFEB intensities between nuclei and cytoplasm was calculated in (H). Data are means ± SD (*** = p < 0.001 versus Ctr; ###=p<0.001 versus WT/3,4-DC). Representative images are shown in (G). Scale bar equals 10 µm.",
    "ncbi_link": "TSC2: 22084"
  },
  {
    "caption": "MEF wild type and TSC2 knockout (TSC2 KO) cells were treated with 3,4-DC for 6 h. (I) After the treatment, nuclei were isolated and western blot was performed to detect nuclear and cytosol TFEB protein levels.",
    "ncbi_link": "TSC2: 22084"
  },
  {
    "caption": "(J-L) MEF wild type and TSC2 KO cells were collected and lysed for western blot after the treatment with 3,4-DC. Antibodies against LC3, p62, TSC2, or GAPDH were administrated to detect protein levels, and phosphorylation of mTOR substrate p70 S6K at Threonine 389 (T389) was measured with the phosphorylation specific antibody (P-p70(T389)) and anti-p70 antibody. The bands intensities of LC3-II, p62, and GAPDH were measured with Image J, and the ratios of LC3-II/GAPDH and p62/GAPDH were calculated in (K) and (L). Data are means ± SEM of at least three independent experiments (** = p < 0.01, *** = p < 0.001 vs Ctr; #=p<0.05, ##=p<0.01 vs WT/3,4-DC)",
    "ncbi_link": "TSC2: 22084"
  },
  {
    "caption": "U2OS-GFP-LC3 cells transfected with 3 individual siRNAs specifically targeting TFEB (siTFEB-#1, siTFEB-#2, siTFEB-#3) or scrambled siRNA (siCtr) were treated with 3,4-DC as indicated for 16 h. TFEB knockdown efficiency by TFEB siRNAs and TFEB deficiency by knockout were checked by SDS-PAGE and immunoblot",
    "ncbi_link": "GFP: 
LC3: 81631
TFEB: 7942"
  },
  {
    "caption": "U2OS-GFP-LC3 cells transfected with 3 individual siRNAs specifically targeting TFEB (siTFEB-#1, siTFEB-#2, siTFEB-#3) or scrambled siRNA (siCtr) were treated with 3,4-DC as indicated for 16 h. GFP-LC3 dots were quantified as indicator of autophagy Data are means ± SD (* = p < 0.05, ** = p < 0.01 versus siCtr or WT cells treated with 3,4-DC). Representative images are shown Scale bar equals 10 µm.",
    "ncbi_link": "GFP: 
LC3: 81631
TFEB: 7942"
  },
  {
    "caption": "U2OS wild type (wt) and TFEB knockout (TFEB KO) GFP-LC3 cells were treated with 3,4-DC as indicated for 16 h. TFEB knockdown efficiency by TFEB siRNAs and TFEB deficiency by knockout were checked by SDS-PAGE and immunoblot",
    "ncbi_link": "GFP: 
LC3: 81631
TFEB: 7942"
  },
  {
    "caption": "U2OS wild type (wt) and TFEB knockout (TFEB KO) GFP-LC3 cells were treated with 3,4-DC as indicated for 16 h. GFP-LC3 dots were quantified as indicator of autophagy ata are means ± SD (* = p < 0.05, ** = p < 0.01 versus siCtr or WT cells treated with 3,4-DC). Representative images are shown cale bar equals 10 µm.",
    "ncbi_link": "GFP: 
LC3: 81631
TFEB: 7942"
  },
  {
    "caption": "U2OS wild type (WT), TFEB or TFE3 knockout, or double knockout (TF DKO) cells were treated with 30 µM 3,4-DC for 16 h. Following, cells were collected and SDS-PAGE and immunoblots were performed as described before. TFEB, TFE3, LC3, p62, and GAPDH protein levels were measured with specific antibodies (G).",
    "ncbi_link": "TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "U2OS wild type (WT), TFEB or TFE3 knockout, or double knockout (TF DKO) cells were treated with 30 µM 3,4-DC for 16 h. GFP-LC3 dots were quantified as indicator of autophagy (H). Data are means ± SD (* = p < 0.05, ** = p < 0.01, *** = p < 0.001 versus Ctr, respectively).",
    "ncbi_link": "TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "(I) U2OS WT, knockout for TFEB (TFEB-/-) or TFE3 (TFE3-/-), double knockout (DKO) were treated with 3,4-DC for 24 h and stained with LysoTracker Red for 30 min. Thereafter, the red (positive) dots were measured. Data are means ± SD (* = p < 0.05; ** = p < 0.01; *** = p < 0.001).",
    "ncbi_link": "TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "(J) Relative mRNA expression levels of key autophagy genes such as Lamp1, Lc3b and p62 were detected in controls and 3,4-DC treated U2OS cells. Data is depicted as a heatmap showing means of at least three independent experiments (*** = p < 0.001 versus WT/Ctr and # = p < 0.05, ## = p < 0.01, as compared to WT treated with 3,4-DC).",
    "ncbi_link": "Lamp1: 3916
Lc3b: 81631
p62: 8878"
  },
  {
    "caption": "GFP-LC3 expressing mice were i.p. injected with 3,4-DC for 24 h. Leupeptin (Leu) was used to test autophagic flux in vivo and GFP-LC3 dots were measured in liver tissue. Data are means ± SEM of at least three mice (*= p < 0.05 versus ctr without Leu; #= p < 0.05 versus ctr with Leu).",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "GFP-LC3 expressing mice were i.p. injected with 3,4-DC for 24 h. Leupeptin (Leu) was used to test autophagic flux in vivo and GFP-LC3 dots were measured in heart (I, J) tissue. Data are means ± SEM of at least three mice (*= p < 0.05 versus ctr without Leu; #= p < 0.05 versus ctr with Leu).",
    "ncbi_link": "GFP: 
LC3: 81631"
  },
  {
    "caption": "(A) Twelve weeks-old wild-type and cardiac specific Atg7 knockout (Atg7cKO) mice were injected with corn oil (vehicle control, Ctr) or 3,4-DC 24 h before surgery and subjected to 3 h prolonged ischemia. Representative images of left ventricular (LV) myocardial sections after alcian blue and triphenyltetrazolium chloride (TTC) staining are depicted. Scale bar equals 1 mm.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "Growth kinetic of MCA205 fibrosarcomas that were either wild type or Atg5KD (H-I) and were evolving in immunocompetent C57Bl/6 mice or immunodeficient nu/nu mice (G), treated as indicated",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(J-L) Immunocompetent C57Bl/6 mice were subcutaneously inoculated with TFEB/TFE3 double knockdown MCA205 cells or its scramble control cells (K). When tumors became palpable, mice were treated as indicated Tumor growth curves from mice subjected to 3,4-DC administration alone or in combination with MTX are shown (J,L). Asterisks indicate significant effect of MTX with respect to untreated controls (mean value ±SEM, *p<0.05, **p<0.01, ***p<0.001), while hash symbols refer to the comparison of the effects of MTX plus 3,4-DC to MTX alone (#p<0.05, ##p<0.01, ###p<0.001)(n=6-14).",
    "ncbi_link": "TFE3: 209446
TFEB: 21425"
  },
  {
    "caption": "WB analysis of smc5-AID clones in the absence or presence of Auxin using FLAG. Tubulin is used as loading control and wt cells is used as a negative control for the FLAG tag.",
    "ncbi_link": "smc5: 431608"
  },
  {
    "caption": "Proliferation curve of wt and smc5-AID cells in the presence or absence of Auxin. The data represents means ± SD of 3 independent experiments.",
    "ncbi_link": "smc5: 431608"
  },
  {
    "caption": "Proliferation curves of wt and 2 independent smc5 clones grown at 39.5ºC, with the estimated doubling time on the right. Data represents means ± SD of 4 experiments. Asterisks indicate p value ≤ 0.05, as derived from unpaired t-test type 3, two-sample unequal variance, carried out to check statistical significance between smc5 clones and wt. smc5 clone 1 versus wt, p=0.016, smc5 clone 2 versus wt, p=0.04.",
    "ncbi_link": "smc5: 431608"
  },
  {
    "caption": "Bidimensional FACS analysis shows significant accumulation in G2/M and decrease in the S phase in smc5 mutants. The data represents means ± SD of 3 independent experiments for smc5 clones 2 and 3, and 4 independent experiments for wt and smc5 clone 1. Asterisks indicate p value ≤ 0.05, detailed below, using paired t-test. S-phase (smc5 clones 1, 2, 3 versus wt: p= 0.0031; p=0.0002; p=0.004, respectively). G2/M (smc5 clones 1, 2, 3 versus wt: p= 0.029; p=0.0014; p=0.02, respectively).",
    "ncbi_link": "smc5: 431608"
  },
  {
    "caption": "Survival curve of smc5 cells treated with different concentrations of cisplatin (CDDP). Data represents means ± SD of 3 experiments.",
    "ncbi_link": "smc5: 431608"
  },
  {
    "caption": "Survival curve of smc5 cells complemented or not with chicken SMC5 cDNA and treated with different concentrations of cisplatin. The experiment is carried out at 39.5ºC. Data represents means ± SD of at least 3 experiments.",
    "ncbi_link": "smc5: 431608
SMC5: 431608"
  },
  {
    "caption": "Survival curve of smc5 ku70 cells treated with different concentrations of cisplatin. Data represents means ± SD of the 3 experiments.",
    "ncbi_link": "smc5: 431608
ku70: 395767"
  },
  {
    "caption": "Survival curve of smc5 fancc cells treated with different concentrations of cisplatin. Data represents means ± SD of 3 experiments.",
    "ncbi_link": "fancc: 427468
smc5: 431608"
  },
  {
    "caption": "Left panel: Growth curve was carried out to test smc5 fancm cell proliferation. Data represents means ± SD of 3 experiments. Right panel: Survival curve of smc5 fancm cells treated with different concentrations of cisplatin. Data represents means ± SD of the 3 experiments.",
    "ncbi_link": "fancm: 100857997
smc5: 431608"
  },
  {
    "caption": "Clonogenic assay to test cisplatin sensitivity of smc5 fancm cells in long term assays. Data represents means ± SD of 2 independent experiments with two independent clones analyzed for smc5 fancm.",
    "ncbi_link": "fancm: 100857997
smc5: 431608"
  },
  {
    "caption": "Left panel: Growth curve was carried out to test smc5 rad17 (C) cell proliferation. Data represents means ± SD of 3 experiments. Right panel: Survival curve of smc5 rad17 (C) cells treated with different concentrations of cisplatin. Data represents means ± SD of the 3 experiments.",
    "ncbi_link": "rad17: 404778
smc5: 431608"
  },
  {
    "caption": "Left panel: Growth curve was carried out to test smc5 ddx11 (D) cell proliferation. Data represents means ± SD of 3 experiments. Right panel: Survival curve of smc5 ddx11 (D) cells treated with different concentrations of cisplatin. Data represents means ± SD of the 3 experiments.",
    "ncbi_link": "ddx11: 418144
smc5: 431608"
  },
  {
    "caption": "Left panel: Representative Western blots illustrating the expression of SMC6, SMC5 and FANCD2 in protein extracts from HeLa cells 48 hours after transfection with the indicated siRNAs. Right panel: Relative expression of SMC5, SMC6 and FANCD2. We performed individual experiments for each cell line with technical replicates. In each individual experiment, we first normalized SMC5, SMC6 or FANCD2 expression to that of Vinculin (internal control) and calculated its relative level in each cell line in relation to the target protein/Vinculin ratio of the siLacZ transfected cells, which was set as one in each experiment. Data present the mean+/-S.E.M. and were analyzed by unpaired t-test. SMC5 in siSMC6: n=7 and p=0.0002; SMC5 in siFANCD2: n=7 and p=0.0016; SMC6 in siSMC5: n=8 and p<0.0001; SMC6 in siFANCD2: n=24 and p<0.0001; FANCD2 in siSMC6: n=30 and p<0.0001; FANCD2 in siSMC5: n=10 and p=0.0008.",
    "ncbi_link": "LacZ: 
FANCD2: 2177
SMC5: 23137
SMC6: 79677"
  },
  {
    "caption": "Top. Representative images of nuclei (DAPI stained, blue) with RAD51 (green) foci in HeLa cells transfected with the indicated siRNAs and treated with HU or MMC, as indicated in panel A. The scale bar represents 10 μm. Bottom. Histograms presenting the percentage of RAD51 foci-positive cells as evaluated in the different conditions of above. Data represent the means+/-S.E.M. and were analyzed by unpaired t-test. siSMC6 vs siLacZ: n=3, NT, MMC or HU p=n.s.; siFANCD2 vs siLacZ: n=4, NT p=n.s., MMC p=0.0003, HU p=0.0479; siSMC6+siFANCD2 vs siLacZ: n=3, NT p=n.s., MMC p=0.0439, HU p=0.0458.",
    "ncbi_link": "LacZ: 
FANCD2: 2177
SMC6: 79677"
  },
  {
    "caption": "Left panel: Representative images of anaphase HeLa cells with micronuclei (white arrows). 48 hours after transfection with indicated siRNAs cells were incubated 18 hours with 2 μg/ml cytochalasyn B to block cytokinesis. The scale bar represents 20 μm. Right panel: Histograms presenting the percentage of binucleate cells with micronuclei. Data represent the mean +/- SEM of 3 independent experiments, t-test, unpaired. siSMC6 vs siLacZ, p=0.0085; siFANCD2 vs siLacZ, p=0.0057; siSMC6+siFANCD2 vs siLacZ, p=0.0019.",
    "ncbi_link": "LacZ: 
FANCD2: 2177
SMC6: 79677"
  },
  {
    "caption": "Top: Examples of HeLa mitotic catastrophes and anaphase bridges as observed 48 hours after siRNA transfection. The scale bar represents 20 μm. Bottom: Histograms presenting the percentage of cells with mitotic abnormalities. Data represent the mean +/- S.E.M. of 3 independent experiments. t-test, unpaired. siSMC6 vs siLacZ: Aberrant mitosis p=0.0125, Nuclear bridges p=0.0198, Mitotic catastrophes p=0.0145; siFANCD2 vs siLacZ: Aberrant mitosis p=0.0005, Nuclear bridges p=0.0002, Mitotic catastrophes p=0.0011; siSMC6+siFANCD2 vs siLacZ: Aberrant mitosis p=0.0012, Nuclear bridges p=0.0116, Mitotic catastrophes p=0.0033.",
    "ncbi_link": "LacZ: 
FANCD2: 2177
SMC6: 79677"
  },
  {
    "caption": "Immunoprecipitation of FLAG-SMC6 and FLAG-NSMCE2 with FANCI in HEK293T cells overexpressing the SMC6 or NSMCE2, respectively, in the presence or absence of Ethidium bromide (EtBr). The experiment was performed 3 times, and the blot shows a representative experiment. The band under the one indicated as FANCI may represent a degradation product.",
    "ncbi_link": "NSMCE2: 286053
SMC6: 79677"
  },
  {
    "caption": "B. BJ ESCs stably co-expressing H2B-GFP (green) and mCherry-H2B (red), hereafter named BJH2B-2FPs. C. ChIP-qPCR analysis of GFP enrichment inside different repetitive elements (ERV, MajSat, IAPs) used as H3K9me3 domain controls, or at the Hoxa11 gene used as a H3K27me3 domain control, or on transcribed genes (Gapdh, Pou5f1, Actb) or actively transcribed gene promoter (Pou5f1-promoter) in BJ WT and BJH2B-GFP ESCs. Gene names are color-coded in red whether they are associated to heterochromatic domains (enriched in H3K9me3); in black to Polycomb domains (enriched in H3K27me3); in blue to active chromatin domains (enriched in H3K4me3). Data are represented as relative enrichments of H2B-GFP versus histone H2B. Data are means ± s.d (n=3 biological replicates for GFP and histone H2B).",
    "ncbi_link": "GFP: 
H2B: 
mCherry: 
Actb: 60
Gapdh: 2597
Hoxa11: 3207
Pou5f1: 5460"
  },
  {
    "caption": "E. Left panel, in vivo FLIM-FRET assay in BJH2B-2FPs stably co-expressing H2B-GFP (green) and mCherry-H2B (red). Mean FRET efficiency is displayed using a continuous pseudo-colour scale from 0 to 40%. Magnification of the FRET map, with discrete high FRET regions indicated by white arrowheads. Scale bars, 5 µm. Right panel, mean distribution of the FRET efficiency related to the pixel fraction from BJH2B-2FPs cells (n = 384 cells).",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "A. Top and bottom panels depict a representative nucleus of BJH2B-2FPs ESC by GFP intensity (nucleosome concentration) and FRET efficiency, respectively. Yellow arrowheads: regions with high nucleosome density but low FRET efficiency; Orange arrowheads: regions with low nucleosome density but high FRET efficiency. Scale bars,10 μm. The right panel correlates FRET efficiency with GFP fluorescence intensity (Pearson correlation coefficient, r = -0.07, n = 106 cells).",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "F. Top and bottom panels depict a representative nucleus of BJH2B-2FPs ESC after 15 min of ATP depletion by GFP intensity (i.e., nucleosome concentration) and FRET efficiency, respectively. Yellow arrows indicate nucleosome-rich foci associated with high levels of FRET. Scale bars,10 µm. The FRET efficiencies (%) from nucleosome-rich foci in untreated and ATP-depleted cells are depicted as Box-and-Whisker plots. The thick line represents median, the boxes correspond to the FRET efficiency (%) values from the 25-75th percentiles of the median, and the whiskers cover the Minimum to Maximum value range. ****, p < 0.0001 (Mann-Whitney test, n = 61 cells). Mean distribution of the FRET efficiency of BJH2B-2FPs from nucleosome-rich foci in untreated (black, n = 162) and ATP-depleted cells (red, n = 61 cells). ****, p = 2.2e-16; K-S test.",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "G. Left panel, representative image of in vivo FLIM-FRET measurements from differentiated 3T3 cells co-expressing H2B-GFP and mCherry-H2B. Yellow arrows indicate high FRET efficiencies at H2B-GFP bright chromocenters. Scale bars, 10 µm. Right panel, comparison of the FRET efficiency (%) from ESCs (blue) and 3T3 cells (white) in the GFP-brightest foci (nucleosome-rich foci). FRET efficiency (%) was represented as Box-and-Whisker plots. The thick line represents median, the boxes correspond to the FRET % values from the 25-75th percentiles of the median, and the whiskers cover the Minimum to Maximum value range. ****, p < 0.0001 (Mann-Whitney test, n = 42 cells).",
    "ncbi_link": "GFP: 
H2B: 
mCherry: "
  },
  {
    "caption": "A. Expression of mTagBFP-tagged HP1α in living BJH2B-2FPs and segmentation of HP1α positive foci. Yellow arrowheads: chromocenters enriched in H2B-GFP (left panel), in mTagBFP-HP1α (middle panel), and following segmentation (right panel). B. Box plot of the mean FRET efficiencies of all nucleosome-rich foci (black, n = 68 cells) and foci enriched in HP1α (blue, n = 68 cells). FRET efficiency (%) was represented as Box-and-Whisker plots. The thick line represents median, the boxes correspond to the FRET % values from the 25-75th percentiles of the median, and the whiskers cover the 10-90 percentiles value range. **** p < 0.0001, Mann-Whitney test.",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "A. Total cell extracts from BJH2B-2FPs cells incubated during 24h with untargeted siRNA or an siRNA targeting HP1α, analyzed by western blotting with an antiserum against HP1α. Loading control was performed by red ponceau staining.",
    "ncbi_link": "H2B: 
HP1α: 23468"
  },
  {
    "caption": "C. Left panel, mean distribution of the FRET efficiency from nucleosome-rich foci of BJH2B-2FPs cells incubated with a control siRNA (black, n = 101 cells) or an siRNA against HP1β (green, n = 136 cells); *, p: 0.02651; K-S test. Right panel, box plot of the mean FRET efficiency from nucleosome-rich foci of living of BJH2B-2FPs cells incubated with a control siRNA (grey, n = 101 cells) or an siRNA against HP1β (green, n = 136 cells). Box-and-Whisker plots represent the FRET efficiency (%). The thick line represents median, the boxes correspond to the FRET % values from the 25-75th percentiles of the median, and the whiskers cover the Minimum to Maximum value range.",
    "ncbi_link": "H2B: 
HP1β: 10951"
  },
  {
    "caption": "F. Total cell extracts from untreated, DMSO treated or A-196 treated BJH2B-2FPs during 24h or 48h, analysed by western blotting with antibody against H4K20me3. Arrowhead indicates the H4K20me3-specific bands. The asterisk indicates unspecific bands.",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "A. Representative images of immunostainings for Ki-67 in mitotic WT, control (CTRL) and Mki67-/- ESCs. Scale bar, 10 µm.",
    "ncbi_link": "Mki67: 4288"
  },
  {
    "caption": "B. Box-and-Whisker plots represent the FRET efficiency (%) from control mitotic ESCs (n = 12 cells) and from three different Mki67-/- ESCs clones named #1 (n = 10 cells), #2 (n = 9 cells) and #3 (n = 8 cells). The thick line represents median, the boxes correspond to the FRET % values from the 25-75th percentiles of the median, and the whiskers cover the 10-90 percentiles value range; ***, p = 0.0007; ****, p < 0.0001, Mann-Whitney test.",
    "ncbi_link": "Mki67: 4288"
  },
  {
    "caption": "C. Left panel, in vivo FLIM-FRET measurements in interphase BJH2B-2FPs control ESCs (top) and BJH2B-2FPs Mki67-/- ESCs (clone #1). Mean FRET efficiency is displayed using a continuous pseudo-colour scale from 0 to 25%. Scale bars, 10 µm. Right panel, box-and-Whisker plots represent the FRET efficiency (%) in WT ESCs (n = 77 cells) and Mki67-/- ESCs clones clone #1 (n = 86 cells), #2 (n = 95 cells) and #3 (n = 110 cells). The thick line represents median, the boxes correspond to the FRET % values from the 25-75th percentiles of the median, and the whiskers cover the 10-90 percentiles value range. ****, p < 0.0001, Mann-Whitney test.",
    "ncbi_link": "H2B: 
Mki67: 4288"
  },
  {
    "caption": "B. Left panels, nucleosome-rich foci segmentation in naive ESCs and EpiLCs using the FRENETIC tool. Nuclei are outlined with yellow dashed lines. Scale bars, 10µm. Right panel, Box-and-Whisker plots of the mean number of foci per nucleus in naive BJH2B-2FPs ESCs (n = 150 cells) and in primed EpiLCs (n = 137 cells). The thick line represents median, the boxes correspond to the number of foci from the 25-75th percentiles of the median",
    "ncbi_link": "H2B: "
  },
  {
    "caption": "Strep-Tactin pull down  of GIDAnt (strep-tagged at Gid8 C-terminus) probing binding  of Gid1057-292 and Gid4117-362 to the complex visualized with Coomassie-stained SDS-PAGE. The experiment was performed with WT and C-terminal deletion (∆C) of the substrate receptors (∆289-292 (FEIA) and ∆359-362 (FEFA) for Gid10 and Gid4, respectively) and WT and mutant (mut, Gid5W606A/Y613A/Q649A) GIDAnt.",
    "ncbi_link": "Gid5: 854795"
  },
  {
    "caption": "Lysates from wildtype and ∆Gid2 yeast  strains expressing endogenously tagged 3xFLAG-Gid10 that were grown at 42°C for one hour, and then returned to 30°C for the indicated timepoints  were run on an SDS-PAGE gel and immunoblotted  with αFLAG and αPGK.",
    "ncbi_link": "Gid2: 851842"
  },
  {
    "caption": "Lysates from wildtype, Gid5W606A,Y613A,Q649A, and Gid10∆C strains expressing endogenously tagged 3xFLAG-Gid10 that were grown at 42°C for one hour, and then returned to 30°C for the indicated timepoints  were run on an SDS-PAGE gel and immunoblotted  with αFLAG and αPGK.",
    "ncbi_link": "Gid10: 852957
Gid5: 854795"
  },
  {
    "caption": "Lysates from wildtype, ∆Gid4, and Gid4∆C strains expressing endogenously tagged 3xFLAG-Gid10 that were grown at 42°C for one hour, and then returned to 30°C for the indicated timepoints  were run on an  SDS-PAGE gel and immunoblotted  with αFLAG  and αPGK.",
    "ncbi_link": "Gid4: 852402"
  },
  {
    "caption": "Wildtype and  Gid10 overexpressing yeast  strains expressing  endogenously tagged Gid4 were grown for 19 hours in YPE, and transitioned to YPD  for the indicated timepoints. Lysates were run on an SDS-PAGE gel and immunoblotted  with αFLAG  and αPGK. Points represent mean, error bars represent standard deviation (n>3 biological replicates).",
    "ncbi_link": "Gid10: 852957"
  },
  {
    "caption": "A. RT-PCR analysis of the expression of β-actin, Trpv1, Trpv2, Trpv3 and Trpv4 using mouse differentiated brown adipocytes after 29 (upper) and 35 (lower) thermal cycles with (RT (+)) and without (RT (-)) reverse transcription (RT). Control (Ct.) lanes indicate the results with each plasmid DNA as a template.",
    "ncbi_link": "β-actin: 11461
Trpv1: 193034
Trpv2: 22368
Trpv3: 246788
Trpv4: 63873"
  },
  {
    "caption": "B. Results of real-time RT-PCR analysis of Trpv1, Trpv2, Trpv3 and Trpv4 expression using mouse differentiated brown adipocytes. Expression levels of mRNA were normalized to that of the ribosomal protein gene (36B4), a housekeeping gene un-affected by adipogenesis. Data are presented as mean ± SEM, n = 6.",
    "ncbi_link": "36B4: 
Trpv1: 193034
Trpv2: 22368
Trpv3: 246788
Trpv4: 63873"
  },
  {
    "caption": "C. Results of real-time PCR analysis of Trpv1, Trpv2, Trpv3 and Trpv4 expression using mouse interscapular brown adipose tissue (iBAT). mRNA expression levels were normalized to that of 36B4. Data are presented as mean ± SEM, n = 5.",
    "ncbi_link": "36B4: 
Trpv1: 193034
Trpv2: 22368
Trpv3: 246788
Trpv4: 63873"
  },
  {
    "caption": "D. Western blot results of TRPV2 and tubulin from WT and TRPV2KO brown adipocytes. Upper bands in the TRPV2 blots likely indicate glycosylated forms.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "E. Averaged traces of [Ca2+]i changes in response to 500 µmol/L 2APB in differentiated brown adipocytes from WT (black) and TRPV2KO (red) mice. One µmol/L NE was used to confirm differentiation. Five µmol/L ionomycin was used to confirm cell viability. Ratio values correspond to the real [Ca2+]i of differentiated mousebrown adipocytes. Data are presented as mean ± SEM, n = 149 of WT cells, and n = 112 of TRPV2KO brown adipocytes; ** P < 0.01. Unpaired Student's t-test.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "A. Results of real-time RT-PCR analysis of Trpv1, Trpv2, Trpv3 and Trpv4 expression in mouse pre-adipocytes and differentiated brown adipocytes. Expression levels of mRNA were normalized to those of 36B4. Data are presented as mean ± SEM, n = 6. * P < 0.05 vs. pre-adipocytes. Unpaired Student's t-test.",
    "ncbi_link": "36B4: 
Trpv1: 193034
Trpv2: 22368
Trpv3: 246788
Trpv4: 63873"
  },
  {
    "caption": "C and D. Comparison of the numbers of 6 day-differentiated mouse brown adipocytes (C) and triglyceride levels (D) in the cells from WT and TRPV2KO mice with different differentiation media. 1/10 suppl. indicates differentiation medium ten-time-diluted with DMEM. Mean ± SEM, n = 8, ** P < 0.01 vs. control group, ##P < 0.01 vs. WT group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "A. Basal mRNA expression of Ucp1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α), peroxisome proliferator-activated receptorγ(Pparγ) and β3-adrenergic receptor 3 (Adrb3) in the differentiated brown adipocytes from WT and TRPV2KO mice. Data are presented as mean ± SEM, n = 5; ** P < 0.01 vs. WT. Unpaired Student's t-test.",
    "ncbi_link": "Adrb3: 11556
Pparγ: 19016
Pgc1α: 19017
TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "B and C. Changes in Ucp1 (B) and Pgc1α(C) mRNA expression in the differentiated brown adipocytes from WT and TRPV2KO mice with and without 10 µmol/L isoproterenol (ISO) for 4 h. Data are presented as mean ± SEM, n = 5; ** P < 0.01 vs. DMSO group; # P < 0.05; ## P < 0.01 vs. WT group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "Pgc1α: 19017
TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "D and E. Changes in Ucp1 mRNA expression (D) and non-esterified fatty acid (NEFA) release (E) in the differentiated brown adipocytes from WT and TRPV2KO mice with or without 10 µmol/L forskolin for 4 h. Data are presented as mean ± SEM, n = 6; * P < 0.05; ** P < 0.01 vs. DMSO group; ## P < 0.01 vs. WT group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "F and G. Changes in Ucp1 mRNA (F) and Pgc1α mRNA (G) in the differentiated brown adipocytes treated with 10 µmol/L ISO alone or 10 µmol/L ISO plus 10 µmol/L BAPTA-AM for 4 h. Data are presented as mean ± SEM, n = 6; * P < 0.05; ** P < 0.01 vs. DMSO group; ## P < 0.01 vs. ISO group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "Pgc1α: 19017
Ucp1: 22227"
  },
  {
    "caption": "B and C. Changes in food intake (B) and water intake (C) from 3-weeks to 8-weeks of ages between WT and TRPV2KO mice (n = 6).",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "D. Weights of tissues related to energy metabolism normalized to their body weights in WT and TRPV2KO mice (n = 15).",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "E. The expression levels of mRNA related to energy metabolism in iBAT from WT and TRPV2KO mice. mRNA expression levels of Ucp1, Pgc1a, Ppary, Adrb3, cytochrome c oxidase subunit 4 isoform 1 (Cox4i1), PR domain containing 16 (Prdm16), Ucp2, lipoprotein lipase (Lpl) and cluster of differentiation 36 (Cd36) were examined and normalized to the levels of 36B4. Data are presented as mean ± SEM, n = 15; * P < 0.05 vs. WT group; ** P < 0.01 vs. WT group. Unpaired Student's t-test.",
    "ncbi_link": "36B4: 
Adrb3: 11556
Cd36: 12491
Cox4i1: 12857
Lpl: 16956
Ppary: 19016
Pgc1a: 10891
Prdm16: 70673
TRPV2: 22368
Ucp1: 22227
Ucp2: 22228"
  },
  {
    "caption": "A. Representative morphological results of iBAT by hematoxylin and eosin staining from 8-week WT and TRPV2KO mice. Scale bars indicate 100 μm.B. Comparison of lipid droplet size histograms from 8-week-old WT (black) and TRPV2KO (red) iBAT with hematoxylin and eosin staining. Mean values are 9.5 ± 0.2 µm in 8-week-old WT adipocytes, and 14.7 ± 0.2 µm in 8-week-old TRPV2KO adipocytes (P < 0.01). 1000 to 1400 droplets were counted. Data are presented as mean ± SEM, n = 4.C. Comparison of adipocyte size histograms from 8-week-old WT (black) and TRPV2KO (red) iBAT with hematoxylin and eosin staining. 800 to 1000 cells were counted. Data are presented as mean ± SEM, n = 4.D. Mean diameters of adipocytes in 8-week-old WT mice (black) and TRPV2KO mice (red). Mean values are 15.8 ± 0.4 µm in 8-week-old WT adipocytes, and 19.8 ± 0.3 µm in 8-week-old TRPV2KO adipocytes. Data are presented as mean ± SEM, n = 4; * P < 0.05 vs. WT group. Unpaired Student's t-test.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "A, B, C and D. Changes in mRNA expression of Ucp1 (A), Pgc1α (B), Pparγ (C) and Trpv2 (D) in iBAT of WT and TRPV2KO mice before (25oC), after 1 day and 3 days cold (4oC) exposure. Mean ± SEM, n = 5 - 8; * P < 0.05; ** P < 0.01 vs. 25oC group; # P < 0.05 vs. WT group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "Pparγ: 19016
Pgc1α: 19017
Trpv2: 22368
TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "E and F. Western blot results of UCP1 protein in iBAT from WT and TRPV2KO mice before (25oC) and after 3 days cold (4oC) exposure (E). Comparison of UCP1 protein levels before and after cold exposure in iBAT from WT and TRPV2KO mice (F). Mean ± SEM, n = 6; * P < 0.05 vs. 25oC group; # P < 0.05 vs. WT group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "G and H. Averages of core body temperatures (G) and activities (H) of WT and TRPV2KO mice with or without cold (4oC) exposure. Data are presented as mean ± SEM, n = 5; * P < 0.05 vs. WT group. Unpaired Student's t-test.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "A, B and C. Changes in mRNA expression of Ucp1 (A), Pgc1α (B) and Pparγ(C) from WT and TRPV2KO iBAT 4 h after intraperitoneal administration (i.p., arrows) of saline or a selective β3-adrenergic receptor agonist, BRL37344 (600 µg/kg body weight). Mean ± SEM, n = 5 - 7; * P < 0.05 vs. saline group; # P < 0.01 vs. WT BRL37344 administration group. One-way ANOVA followed by 2-tailed t-test with Bonferroni correction.",
    "ncbi_link": "Pparγ: 19016
Pgc1α: 19017
TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "D and E. Average traces of changes in iBAT temperature (D) or rectal body temperature (E) from WT and TRPV2KO mice after BRL37344 (600 µg/kg body weight) administration (i.p., arrows). Mean ± SEM, n = 5. * P < 0.05 vs. WT group. Unpaired Student's t-test.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "F and G. iBAT NE turnover rates (F) and rate constants k (G) in WT and TRPV2KO mice upon cold exposure (4oC) for 4 h. Data are presented as mean ± SEM, n = 8.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "A. Body weight changes between WT and TRPV2KO mice treated with high fat diet (HFD) for continuous 8 weeks from 13-week-old.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "B and C. Blood glucose level (B) and plasma insulin level (C) of WT and TRPV2KO mice after 8-week HFD treatment.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "D. Weights of tissues related to energy metabolism in WT and TRPV2KO mice after 8-week HFD treatment.",
    "ncbi_link": "TRPV2: 22368"
  },
  {
    "caption": "E. mRNA expression of Ucp1 and Pgc1α in iBAT from WT and TRPV2KO mice after 8-week HFD treatment. All data are presented as mean ± SEM, WT mice (n = 6), TRPV2KO mice (n = 8); * P < 0.05; ** P < 0.01 vs. WT group. Unpaired Student's t-test.",
    "ncbi_link": "Pgc1α: 19017
TRPV2: 22368
Ucp1: 22227"
  },
  {
    "caption": "(a) Western blot analysis showing the replacement of endogenous Beclin 1 with Beclin 1-EGFP in Becn1-/-;Becn1-EGFP/+ mice, as detected by an anti-Beclin 1 antibody.",
    "ncbi_link": "Beclin 1: 56208
Becn1: 56208"
  },
  {
    "caption": "(b) Coomassie-stained SDS-PAGE showing the Beclin 1-interacting proteins immuno-isolated from brain and liver of the 'rescued' mice (lanes 2 and 4) and of control Becn1+/- littermates (lanes 1 and 3), using an anti-GFP antibody. Proteins in the gel bands were extracted and identified by mass spectrometry as Vps15/p150 (band 1), Vps34/class III PI(3)K (band 3), UVRAG (band 4), Beclin 1-EGFP (band 5), Atg14L (band 6, asterisk, gi|27369860) and Rubicon (band 2, asterisk, gi|45708948). UVRAG levels varied with different affinity-purification conditions, suggesting an unstable association of UVRAG with the complex.",
    "ncbi_link": "Beclin 1: 56208
Becn1: 56208"
  },
  {
    "caption": "(d) Western blot analysis of Atg14L, Rubicon, Vps34 and Beclin 1 in gel filtration fractions from wild-type mouse liver extract showed co-elution of these proteins in fractions 38-45. Atg14L was also eluted in later fractions 51-56. The fractions for the peak elution of thyroglobulin (670K) and γ-globulin (158K) are indicated by arrows. Control siRNA-transfected NIH 3T3 cell lysate was loaded as a positive control (labelled as 1) for the migration position of the Atg14L protein on SDS-PAGE; Atg14L siRNA-transfected NIH 3T3 cell lysate was loaded as a negative control (labelled as 2).",
    "ncbi_link": "Atg14L: 100504663"
  },
  {
    "caption": "(a) Beclin 1 or Atg14L siRNA reduced Atg14L levels and increased p62/SQSTM1 and LC3 II levels under normal and nutrient-starvation conditions in NIH 3T3 cells.",
    "ncbi_link": "Atg14L: 100504663
Beclin 1: 56208"
  },
  {
    "caption": "(b) Compared with control siRNA, Atg14L siRNA decreased long-lived protein degradation in NIH 3T3 cells under normal (*P = 0.007) and starvation (*P = 5 × 10−6) conditions (one-tailed Student's t-test with equal variances, n = 4). This difference was diminished when the starved cells were treated with 3-methyladenine (3MA, 10 mM), a PI(3)K inhibitor.",
    "ncbi_link": "Atg14L: 100504663"
  },
  {
    "caption": "(c) Vps34 kinase assay. HEK 293T cells were co-transfected with Myc-Vps34-Vps15 and Flag-Atg14L or Flag vector, either in the absence or in the presence of Beclin 1-EGFP. Myc-Vps34-Vps15 was immunoprecipitated by anti-Myc antibody for the in vitro kinase assay. The resulting radioactive PI(3)P was separated by thin-layer chromatography (TLC), quantified and normalized against the amount of immunoprecipitated Myc-tagged Vps34 as measured by western blot (upper panel). The quantified results (lower panel) show that overexpressing Atg14L significantly upregulated Vps34 kinase activity by 2.5-fold, but only when Beclin 1 was also overexpressed (*P = 0.04, one-tailed Student's t-test with unequal variances, n = 5).",
    "ncbi_link": "Atg14L: 22863
Beclin 1: 8678
Vps34: 5289
Vps15: 30849"
  },
  {
    "caption": "(e) Electron microscopy images show large structures (asterisks) that are often enwrapped with double membranes in the HEK 293T cells co-transfected with Atg14L-EGFP and Beclin 1-AsRed: concentric membrane 'rings' (panel 1); two large structures (3-5 μm in diameter, panel 2) containing material with high electron density (inset, enwrapping double membranes); numerous autophagosomes (arrows, panel 3) in the cytoplasm; immuno-electron microscopy image of a Atg14L-Beclin 1 structure (labelled with anti-GFP antibody and developed by DAB, panel 4) enwrapped with concentric membrane 'rings'. M, mitochondria; N, nucleus. Scale bar, 500 nm.",
    "ncbi_link": "Atg14L: 22863
Beclin 1: 8678"
  },
  {
    "caption": "(b) Overexpression of Rubicon resulted in increased levels of p62 under both normal and nutrient-starved conditions in HEK 293 cells either stably expressing (upper rows) or transiently transfected with (lower rows) Rubicon-EGFP. The control cells were either stably expressing or transiently transfected with the EGFP-N3 vector.",
    "ncbi_link": "N3: 
Rubicon: 9711"
  },
  {
    "caption": "(c) Vps34 kinase activity. HEK 293T cells were co-transfected with Myc-Vps34-Vps15 and Flag-Rubicon or Flag vector, either in the absence or in the presence of Beclin 1-EGFP. Myc-Vps34-Vps15 was immunoprecipitated by an anti-Myc antibody and used for the in vitro kinase assay. The resulting radioactive PI(3)P was separated by TLC, quantified and normalized against the amount of immunoprecipitated Myc-tagged Vps34, as measured by western blotting (upper panel). The quantified results (lower panel) show that overexpressing Rubicon significantly downregulated the Vps34 kinase activity to 0.58-fold, but only without Beclin 1 overexpression (*P = 0.04, one-tailed Student's t-test with unequal variances, n = 4).",
    "ncbi_link": "Beclin 1: 8678
Rubicon: 9711
Vps34: 5289
Vps15: 30849"
  },
  {
    "caption": "(d) Effect of overexpressing Flag-Rubicon on autophagosome acidification, as monitored by mCherry-GFP-LC3 fluorescence. HeLa cells were transiently co-transfected with mCherry-GFP-LC3 and Flag-Rubicon (or control Flag vector). Cells co-expressing mCherry-GFP-LC3 and control Flag vector contained many red-only puncta along with yellow (indicating the presence of both red and green) puncta, suggesting the presence of both autolysosomes and nascent autophagosomes (upper panel). In contrast, cells co-expressing mCherry-GFP-LC3 and Flag-Rubicon contained primarily yellow or white puncta, suggesting the presence of only nascent autophagosomes (lower panel, white arrows). Notably, some cells, which were co-transfected with mCherry-GFP-LC3 and Flag-Rubicon but expressed high levels of mCherry-GFP-LC3 and undetectable levels of FLAG-Rubicon, contained many red-only puncta (lower panel, yellow arrows). (e) Quantification of the results in d show that overexpressing Flag-Rubicon markedly reduced the percentage of red-only puncta (mCherry-LC3) from 39% in the control Flag vector-transfected cells to 2% in the Flag-Rubicon-transfected cells (*P = 2 × 10−26, one-tailed Student's t-test with unequal variances, n = 30), indicating that overexpression of Rubicon blocks autophagosome acidification or maturation. See Supplementary Information, Fig. S6 for full scans of blots in a-c.",
    "ncbi_link": "Rubicon: 9711
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) Colocalization of Rubicon-EGFP-associated structures with the late endosome/lysosome marker Lamp1 (arrows) in HeLa cells transfected with Rubicon-EGFP. Note that some of the Rubicon-EGFP-associated structures show a 'ring' shape (yellow arrows). Scale bar, 10 μm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(b) Partial colocalization of Rubicon-EGFP-associated structures with the MVB marker LBPA (arrows) in HeLa cells transfected with Rubicon-EGFP. Scale bar, 10 μm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(c) Representative ultrastructural images show aberrant expansion of late endosomal/lysosomal structures in HEK 293T cells overexpressing Rubicon-EGFP. These abnormal organelles are large in size, with high (orange arrows) or low (black arrows) electron density. Some enclose small vesicles (purple arrows) and some resemble the MVB (blue arrows). Scale bars, 500 nm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(d) Representative ultrastructural images show late endosome/lysosome-like structures that are labelled with anti-GFP gold particles (panels 3, 4) in HEK 293T cells transiently transfected with Rubicon-EGFP. These structures are enwrapped by double membranes (panel 4 inset) and co-labelled by anti-GFP (developed by DAB) and anti-Lamp1 (gold enhanced) (panels 5-7) antibodies. Note that mitochondria are mostly negative for Rubicon-EGFP (panel 4). The negative controls are without antibody (panels 1-2). M, mitochondria. Scale bars, 200 nm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(c) Subcellular localization of transiently transfected Rubicon-EGFP, RubiconΔRUN-EGFP, RubiconΔC-EGFP or RubiconΔRUNΔC-EGFP in HeLa cells. In contrast to punctate Rubicon-EGFP and RubiconΔRUN-EGFP, RubiconΔC-EGFP and RubiconΔRUNΔC-EGFP were dispersed in the cytoplasm. ΔRUN, RUN domain deletion; ΔC, cysteine-rich domain deletion. Scale bars, 10 μm.",
    "ncbi_link": "Rubicon: 9711"
  },
  {
    "caption": "(d, e) Absence of full-length Beclin 1 (d) or Beclin 1-CE mutant (e) (red) on the Rubicon-EGFP-positive structures (green) in HEK 293 cells stably expressing Rubicon-EGFP. These cells were transiently transfected with either Beclin 1-AsRed (d) or Flag-Beclin 1-CE (e; that is, the Flag-tagged Beclin 1 mutant containing both CCD and ECD, which mediate the Beclin 1-Rubicon interaction as shown in Supplementary Information, Fig. S3h). Scale bars, 10 μm.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(f) The formation of the Rubicon-EGFP-positive structures was not affected by siRNA knockdown of Beclin 1 in HEK 293 cells stably expressing Rubicon-EGFP.",
    "ncbi_link": "Beclin 1: 8678
Rubicon: 9711"
  },
  {
    "caption": "mtON-expressing animals in a complex I mutant background (gas-1) were scored for locomotion speed in the presence of food by counting body bends per minute. mtON activation rescued the decreased locomotion of the gas-1 mutant background, one-way ANOVA with Tukey's post hoc test, -ATR, +light vs. +ATR, +light *p = 0.0145, +ATR, +light vs. wildtype (WT) *p = 0.0008 (-ATR, -light vs +ATR, +light p = 0.0272, +ATR, -light vs. +ATR, +light p = 0.0332, all conditions vs WT, p < 0.001, n = 30, 30,30,41,41 animals each bar from left to right). Data show mean ± standard deviation.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "Locomotion was assessed by counting body bends per minute. Wild type animals were compared to aak-2(ok524) mutant animals. 2-sample, 2-tailed unpaired t-test *p < 0.0001, wild type n = 35, aak-2 n = 39 animals across at least 3 days. Data show mean ± standard deviation.",
    "ncbi_link": "aak-2: 181727"
  },
  {
    "caption": "(C) Immunocytochemistry showing post-synaptic marker PSD-95 (red), pre-synaptic marker Synapsin-I (green), dendritic marker Map2 (blue) and co-localization of PSD-95 and Synapsin-I from dissociated Nedd4-2 WT or Nedd4-2 cKO hippocampal neurons at DIV 16. Representative secondary dendrites (left) and quantification of colocalized synaptic puncta number and area (right) (n = 36 for Nedd4-2 WT and Nedd4-2 cKO neurons) are shown. Scale bar: 5 µm.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(F) A train of high frequency stimulation (HFS; 100 Hz for 1s) induced early-phase LTP (E-LTP) at Schaffer collateral synapses in Nedd4-2 WT (n = 7 slices from 6 mice) and Nedd4-2 cKO (n = 6 slices from 5 mice) mice. Representative fEPSP traces were recorded before and 60 min after LTP induction (Scale bars: 0.5 mV, 5 ms). Summary bar graphs showing the fEPSP slopes measured 50-60 min after a HFS at Schaffer collateral synapses was on the right. (G) Late-phase LTP (L-LTP) induced by four trains of HFS in Nedd4-2 WT slices (n = 7 slices from 7 mice) and Nedd4-2 cKO slices (n = 9 slices from 8 mice). Representative fEPSP traces were recorded before and 180 min after LTP induction (Scale bars: 0.5 mV, 5 ms). Summary bar graphs showing the fEPSP slopes measured 160-180 min after L-LTP induction at Schaffer collateral synapses was on the right. ",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(B) Barnes maze test from Nedd4-2 WT (n = 8) or Nedd4-2 cKO (n = 8) mice (6-8 weeks old). Schematic representation of Barnes maze (top left). Mice were trained for 4 days with three training trials on each day to locate the escape box (black circle). Learning curve during 4 training days was shown by the escape latency and the number of errors before escaping (top right). Schematic representation of Barnes maze on probe trials (bottom left). Quadrant occupancy on probe trial at day5 and at day12 (bottom right) were assessed by the time spent in the target area (green quadrant).",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(B) Western blots of F-actin to G-actin ratio with or without cLTP induction from Nedd4-2 WT or Nedd4-2 cKO cultured neurons. Schematic representation of the experimental design for cLTP inductions (top left). Representative western blots (bottom left) and quantification of F-actin to G-actin from Nedd4-2 WT or Nedd4-2 cKO (right) cultures after cLTP induction and recovery in normal aCSF for 10 or 30 min before lysis (n = 11 and 8 for Nedd4-2 WT and Nedd4-2 cKO cultures, respectively). For quantification, data from cLTP induction were normalized to data from control (CTL) condition.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(A) Western blots of Nedd4-2, total cofilin, phospho (p)-cofilin and GAPDH from Nedd4-2 WT or Nedd4-2 cKO forebrains at postnatal day 14. Representative western blots and quantification of total cofilin relative to GAPDH and p-cofilin relative to total cofilin (n = 6 for Nedd4-2 WT and Nedd4-2 cKO brains) were shown.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(B) Immunocytochemistry of cofilin, p-cofilin and dendritic marker MAP2 from Nedd4-2 WT or Nedd4-2 cKO cultured hippocampal neurons at DIV 16. Representative dendrites of Nedd4-2 WT and Nedd4-2 cKO neurons and quantification of total cofilin relative to MAP2 and p-cofilin relative to total cofilin are shown (n = 25 and 26 for Nedd4-2 WT and Nedd4-2 cKO neurons, respectively). Scale bar: 5 µm.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(C) Immunocytochemistry showing cofilin, p-cofilin, and dendritic marker MAP2 from Nedd4-2 WT or Nedd4-2 cKO cultured hippocampal neurons induced with or without cLTP at DIV 16. Representative dendrites and quantification from Nedd4-2 WT or Nedd4-2 cKO cultures are shown (n = 36-39 neurons). Scale bar: 5 µm. For quantification, data from cLTP induction were normalized to data from control (CTL) condition.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(A) Immunocytochemistry showing post-synaptic marker PSD-95 (red), pre-synaptic marker Synapsin-I (green), dendritic marker Map2 (blue) and co-localization of PSD-95 and Synapsin-I from Nedd4-2 WT or Nedd4-2 cKO cultured hippocampal neurons at DIV 16 treated with TAT, TAT-S3, or TAT-pS3 peptide for 12 hrs (10 μM). Representative secondary dendrites of Nedd4-2 WT (top left) and Nedd4-2 cKO (bottom left) neurons are shown. Quantification of colocalized synaptic puncta number and synaptic puncta area for Nedd4-2 WT (top right) and Nedd4-2 cKO (bottom right) neurons is on the right (n = 32-36 neurons). Scale bar: 5 µm.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(B) Patch-clamp recordings from Nedd4-2 WT or Nedd4-2 cKO hippocampal neurons treated with TAT, TAT-S3, or TAT-pS3 peptide for 12 hrs (10 μM) at DIV 14-17. Representative mEPSC traces from Nedd4-2 WT (top left) and Nedd4-2 cKO (bottom left) are shown. Quantification of mEPSC amplitude and frequency from Nedd4-2 WT (top right) and Nedd4-2 cKO (bottom right) neurons are shown (n = 22-24 neurons).",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "(C) Barnes maze test after intraperitoneally injecting TAT (n = 8) or TAT-pS3 (n = 8) peptide in Nedd4-2 WT mice (top), or TAT (n = 9) or TAT-pS3 (n = 8) peptides in Nedd4-2 cKO mice (bottom). Learning curve during 4 training days of Barnes maze task showing the escape latency, number of errors before escaping, and the quadrant occupancy on probe trial at day 5 and at day 12 were assessed.",
    "ncbi_link": "Nedd4-2: 83814"
  },
  {
    "caption": "B, Multiplexed activation of Ascl1, Lmx1a, NeuroD1 and of  Ascl1, Lmx1a,  Nr4a2  in  primary astrocytic   cultures. n=3, representative experiment from 2-3 independent experiments, additional data in supplement. Activation levels are depicted as fold change between cells transfected with and without sgRNAs. All levels were normalized to β-Actin. Error bars represent mean ± SD between technical replicates.",
    "ncbi_link": "β-Actin: 11461
Ascl1: 17172
Lmx1a: 110648
NeuroD1: 18012
Nr4a2: 18227"
  },
  {
    "caption": "A, Representative photomicrographs taken from the dorsal striatum 13 weeks after AAV-injection. In  mice injected with GFP  control virus, virtually all GFP positive cells depict an astrocytic morphology, many  GFP positive cells in ALNe-218 and ALN-treated animals show a neuron-like morphology. Data information: Scale bars indicate 20 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B, Immunohistochemical  analysis showing GFP+/GFAP+ double positive cells 13 wpi. Arrows indicate double positive GFP+/GFAP+ cells, arrowheads indicate GFP+/GFAP- cells. Quantification of GFAP+/GFP+ cells shows a significant decrease upon ALNe-218  and ALN-treatment (GFP  vs. ALNe-218 P=0.0064, GFP  vs. ALN  P=0.0002 and ALN  vs. ALNe-218  P=0.0127). Multiple comparison ANOVA F(2,7)=32.06. C,  Double immunostaining  for GFP  and the neuronal  marker NeuN. Arrowheads indicate double positive GFP+/NeuN+ cell 13 wpi. Quantification demonstrate a significant increase in NeuN+/GFP+ cells upon ALNe-218 and ALN-induction (GFP vs.  ALNe-218  P<0.0001, GFP  vs. ALN  P<0.0001 and ALN  vs. ALNe-218 P=0.0012). Multiple comparison ANOVA F(2,6)=170.3. Data information: Scale bars indicate 20 µm. Tukey's multiple comparisons test * P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. n = 3-4 mice  per condition. Error bars represent mean ± SD.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D, Double immunostaining  for GFP  and TH  as a marker for dopaminergic neurons in the  dorsal striatum of GFP-control,  ALNe-218 and ALN-treated animals. Arrowheads indicate GFP+/TH- cells with  neuronal morphology. No GFP+/TH+ cell could be detected in any of the experimental groups. Scale bars indicate 20 µm. Data information: Scale bars indicate 20 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B, RT-qPCR analysis of Ascl1 induction comparing the activation capacity of full-length versus split-dCas9 in Neuro2A cells (data in fold change normalized to non-activated control; dCas9 6116 ± 847.3, split-dCas9 4415 ± 748.8, n=3 biological replicates, box-and-whiskers plots indicate median, 25th-75th percentile and min/max whiskers).",
    "ncbi_link": "Ascl1: 17172
dCas9: 69900935"
  },
  {
    "caption": "C, Immunocytochemistry  analysis of reprogrammed  primary astrocytes   cells 16 days after lentiviral  transduction revealed successful in vitro reprogramming into neurons  using CRISPRa. Astrocytes  are infected with two lentiviruses  expressing dCas9-VPR  in a intein-split version similar to the AAV-dCAS system but driven by a Tet-O promoter. Tet-O driven dsRed  and Ascl1 cDNA expressing construct were used as negative and positive controls respectively. Arrows indicate single MAP2 positive background neurons, arrowheads indicate double positive induced neurons. Scale bar indicates 20 µm. Data information: Abbreviations: OE - overexpression",
    "ncbi_link": "CRISPRa: 
dsRed: 
Tet-O: 
Ascl1: 17172
dCas9: 69900935"
  },
  {
    "caption": "E, Multiplexed activation of  Ascl1/Lmx1a/NeuroD1, Ascl1/Lmx1a/Nr4a2 and Ascl1/ Lmx1a/ Nr4a2/Pitx3/FoxA2 in primary astrocytic  cells. n=2-3 biological replicates, one representative run is shown, additional data in supplement. Activation levels are depicted as fold change between cells transfected with and without sgRNAs. All levels were normalized to β-Actin. Error bars represent mean ± SD between technical replicates.",
    "ncbi_link": "β-Actin: 11461
Ascl1: 17172
FoxA2: 15376
Lmx1a: 110648
NeuroD1: 18012
Nr4a2: 18227
Pitx3: 18742"
  },
  {
    "caption": "A, Representative photomicrographs  taken from the dorsal striatum  13 weeks after AAV-injection. In the GFP  control condition, virtually all GFP  positive cells depict an astrocytic morphology, many GFP  positive cells in ALNe-218 and ALN-treated animals show a neuron-like morphology. Data information: Scale bars indicate 20 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B,  Immunohistochemical  analysis showing GFP+/GFAP+ double positive cells 13 wpi. Arrows indicate double positive GFP+/GFAP+ cells, arrowheads indicate GFP+/GFAP- cells. Quantification of GFAP+/GFP+ cells shows a significant decrease upon ALNe-218 and ALN-treatment (GFP  vs. ALNe-218 P=0.0083, GFP  vs. ALN  P<0.0001 and ALN vs. ALNe-218 P=0.0006, multiple comparison ANOVA F(2,6)=79.76). C, Photomicrographs  showing GFP+/NeuN+ neurons  13 wpi. Arrowheads indicating GFP+/NeuN+ induced neurons. Quantification demonstrate a significant increase in NeuN+/GFP+ cells upon ALNe-218 and ALN-induction (GFP  vs. ALN P=0.0008, ALN vs.  ALNe-218  P=0.0092, multiple comparison ANOVA F(2,7)=21.74). Data information: Scale bars indicate 20 µm. Error bars represent mean ± SD. n = 3-4 mice  (b,c) per condition. Tukey's multiple comparisons test * P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A, Gait analysis using the CatWalk XT system reveals motor defects in 6-OHDA lesion model. Both dCAM and AAV-dCAS  animals transduce with AAV containing specific gRNAs show a significant improvement in different aspects of voluntary movement like the average speed of tread. Naive vs. 6-OHDA P=0.0063. AAV-dCAS: GFP  vs.  ALN P=0.015 multiple comparison ANOVA F(2,17)=12.81) Data information: Statistics: naive vs. 6-OHDA unpaired t-test (two-tailed) * P<0.05, ** P<0.01. GFP  vs ALN, GFP  vs  ALNe-218 and ALN vs ALNe-218 Tukey's multiple comparisons test * P<0.05, ** P<0.01. n = 4-8 mice  per condition.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "the stride length of  front paws: B, Naive vs. 6-OHDA P=0.0164. AAV-dCAS: GFP  vs. ALN  P=0.005, ALN  vs. ALNe-218  P=0.0042, multiple comparison ANOVA F(4,22)=9.9) Data information: Statistics: naive vs. 6-OHDA unpaired t-test (two-tailed) * P<0.05, ** P<0.01. GFP  vs ALN, GFP  vs  ALNe-218 and ALN vs ALNe-218 Tukey's multiple comparisons test * P<0.05, ** P<0.01. n = 4-8 mice  per condition.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "the duty cycle of left front paws. C, Naive vs. 6-OHDA P=0.0096. dCAM: GFP  vs. ALN P=0.036 and ALN vs. ALNe-218 P=0.0252, multiple comparison ANOVA F(2,20)=5.199). Data information: Statistics: naive vs. 6-OHDA  unpaired t-test (two-tailed) * P<0.05, ** P<0.01. GFP  vs ALN, GFP  vs ALNe-218 and  ALN  vs ALNe-218  Tukey's multiple comparisons test * P<0.05, ** P<0.01. n = 4-8 mice  per condition.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D, In contrast to this, dopamine  dependent drug-induced behavior does not show rescue effects: amphetamine-induced  rotation analysis: change in rotational behavior in lesioned animals upon treatment with dopamine  releaser substance. Net rotation = ipsilateral rotation-contralateral rotation (naïve vs. 6-OHDA P=0.09). Data information: Statistics: naive vs. 6-OHDA unpaired t-test (two-tailed) * P<0.05, ** P<0.01. GFP  vs ALN, GFP  vs  ALNe-218 and ALN vs ALNe-218 Tukey's multiple comparisons test * P<0.05, ** P<0.01. n = 4-8 mice  per condition. CatWalk error bars represent mean ± SD. Rotation analysis error bars represent mean ± SEM.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "T cells were collected from age- and gender-matched WT, EGR1KO and EGR4KO mice. (A) CD4+ T cells were isolated from the spleen by negative selection before incubating with anti-CD3/CD28 antibodies for the indicated time periods. Levels of expression of EGR1, EGR2, EGR3 and EGR4 were measured by qPCR.",
    "ncbi_link": "EGR1: 13653
EGR2: 13654
EGR3: 13655
EGR4: 13656"
  },
  {
    "caption": "T cells were collected from age- and gender-matched WT, EGR1KO and EGR4KO mice. (B) WBC were collected from WT, EGR1KO and EGR4KO mice before staining and FACS analysis to determine composition (gating strategies in Appendix Fig S1). Subclasses of CD8+, CD4+ and Treg populations were determined as shown.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "WT and EGR4-/- CD4+ and CD8+ T cells were isolated from the spleen by cell sorting and stained with CFSE. A Cells were incubated under unstimulated conditions or stimulated with either anti-TCRβ or anti-CD3/CD28 antibodies for 0 to 5 days (mean±SEM; a minimum of 3 biological replicates were examined; each biological replicate includes 2 technical replicates).",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "WT and EGR4-/- CD4+ and CD8+ T cells were isolated from the spleen by cell sorting and stained with CFSE. B Dose dependence of EGR4-dependent differences in proliferation were also determined in both CD4+ and CD8+ cells aft er treatment with anti-TCRβ (E,F) or anti-CD3/CD28 (G,H) at the indicated concentrations before FACS analysis (Appendix Fig S2) (mean±SEM; a minimum of 3 biological replicates were examined; each biological replicate includes 2 technical replicates).",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "WT and EGR4-/- CD4+ and CD8+ T cells were isolated from the spleen by cell sorting and stained with CFSE. C,D Generation analysis was then assessed in WT, EGR1-/- and EGR4-/- CD4+ (C) or CD8+ (D) T cells after a 4 day incubation, under unstimulated conditions, or stimulated with either anti-TCRβ or anti-CD3/CD28 antibodies. Generation analysis was determined using FlowJo as depicted in Appendix figure S3 (mean±SEM; a minimum of 3 biological replicates were examined; each biological replicate includes 2 technical replicates).. EGR4 deletion significantly shifted the number of generations as determined by two-way ANOVA; loss of either EGR1 or EGR4 significantly changed the number of generations under resting or stimulated conditions (p < 0.0001).",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "CD4+ and CD8+ T cells were isolated from the spleens of WT, EGR1KO and EGR4KO mice by cell sorting. (A-F) Cytokine secretion was measured by ELISA after incubating CD4+ (A,C,E) and CD8+ (B,D,F) T cells for 48 hrs in resting conditions (A,B) or stimulated with either anti-TCRβ (C,D) or anti-CD3/CD28 antibodies (E,F).",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "CD4+ and CD8+ T cells were isolated from the spleens of WT, EGR4KO mice by cell sorting. (G) Representative FACS plots depicting IFNγ levels after intracellular staining in WT and EGR4KO CD4+ and CD8+ T cells.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ and CD8+ T cells were isolated from the spleens of WT, and EGR4KO mice by cell sorting. (H) Comparison of IFNγ levels in WT vs. EGR4-/- T cells.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated from the spleens of WT, EGR1KO and EGR4KO mice by cell sorting. (I) Representative FACS plots of CD4+ T cells incubated for 24 hrs under Th1 polarizing conditions before intracellular staining with IFNγ and IL-17 antibodies.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated from the spleens of WT, EGR1KO and EGR4KO mice by cell sorting. (J) Comparison of the number of Th1 polarized cells between WT, EGR1-/- and EGR4-/- CD4+ T cells.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated from the spleens of WT, EGR1KO and EGR4KO mice by cell sorting. (K) CD4+ T cells were incubated for 5 days under polarizing conditions before analysis of cytokine production by ELISA.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "(A) NFAT nuclear localization was measured was measured by immunocytochemistry in CD4+ and CD8+ T cells isolated by negative selection from WT, EGR1KO and EGR4KO mice. Cells were stimulated with anti-CD3/CD28 antibodies for the indicated time periods before fixation and staining. Nuclear localization of NFATc1 in CD4+ and CD8+ T cells was determined based on colocalization of NFATc1 and DAPI measured by Pearson analysis (mean±SEM; data are based upon 13 to 20 cells/data point from one experiment; experiment was repeated 3 times). EGR4-mediated differences in NFATc1 localization were determined by two-way ANOVA. NFAT localization was dependent upon EGR4 expression in both CD4+ (p=0.025) and CD8+ (p=0.039) T cells. Post-hoc analysis revealed EGR4-dependent differences at specific timepoints * p < 0.05; *** p < 0.001.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "(B) WT, EGR1KO and EGR4KO CD4+ T cells were isolated from the spleen by negative selection before plating on poly-lysine (control) or CD3/CD28 and loading with fura2. Ca2+ levels shown are from representative single cells measured from multiple experiments. (C) Scatter plots showing area under the curve (AUC) and variance for each cell measured under all conditions.",
    "ncbi_link": "EGR1: 13653
EGR4: 13656"
  },
  {
    "caption": "CD4+ and CD8+ T cells were isolated by negative selection from WT or EGR4-/-mice. (A) CD4+ and CD8+ T cells were loaded with Fura-2AM and plated on poly-D-lysine (2 hrs) before treating with biotinylated anti-CD3ε, followed by streptavidin where indicated. The average response of the majority of CD4+ (WT 74.2±3.2%; EGR4-/- 77.8±2.9%) and CD8+ (WT 79.4±3.5%; EGR4-/- 78.2±2.5%) cells that responded to streptavidin crosslinking of CD3 (mean±SEM; 40-60 cells/coverslip; 7 to 8 separate experiments).",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ and CD8+ T cells were isolated by negative selection from WT or EGR4-/-mice. (B) Cells were plated on anti-CD3/CD28 antibodies for 2 hrs; BTP2 (10 μM) was added where marked by the arrow.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated by negative selection from WT or EGR4-/-mice. (C) CD4+ T cells were incubated with anti-CD3/CD28 antibodies for 6 hrs before measuring expression of IFNγ, IL-2, IL-17 and IL-4 by FACS analysis. Data are mean±SEM; a minimum of 3 biological replicates were examined; each biological replicate includes 2 technical replicates.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated by negative selection from WT, EGR4-/- mice. (A) WT or EGR4-/- cells were loaded with Fura-2AM and plated on anti-CD3/CD28 antibodies for 2 hrs. Senicapoc (4 μM) or Tram-34 (5 μM) were added where marked by the arrow.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated by negative selection from WT, EGR4-/- mice. (B) CD4+ T cells were isolated by negative selection from WT or EGR4-/- mice and incubated with anti-CD3/CD28 antibodies for 6 hrs in the presence or absence of either senicapoc, TRAM-34 or Shk-Dap22 before measuring expression of IFNγ levels by FACS analysis. Data are mean±SEM; 3 biological replicates were examined; each biological replicate includes 2 technical replicates. *** p < 0.001; **** p < 0.0001.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "CD4+ T cells were isolated by negative selection from WT, EGR4-/- mice. (C) To measure the effect of KCa3.1 inhibition of cell proliferation, WT and EGR4-/- CD4+ T cells were isolated from the spleen by cell sorting and stained with CFSE. Cells were incubated with anti-TCRβ antibodies in the presence of vehicle, Senicapoc (5 µM) or TRAM-34 (5 µM) for 4 days and then collected for FACS analysis. (D) Generation analysis was completed for all data using FlowJo software. Data are mean±SEM; 3 biological replicates were examined; each biological replicate includes 2 technical replicates.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. (A) Luciferase expression was monitored by IVIS imaging at the indicated timepoints after luciferin injections. ",
    "ncbi_link": "GFP: 
luciferase: 
EGR4: 13656"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. (B-D) Mice were sacrificed on day 20 and tumors were counted. Data is presented as total/mouse (B), N=9 for each gender and genotype. Differences in luciferase activity measured by IVIS in Panel A were determined by two-way ANOVA. Changes in luciferase activity were significantly altered in EGR4 knockout mice (P < 0.0112).",
    "ncbi_link": "GFP: 
luciferase: 
EGR4: 13656"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. Mice were sacrificed on day 20 and tumors were counted. (B), lung tumors (C) and metastatic tumors (all tumors found outside of the lungs; D). N=9 for each gender and genotype. Differences in luciferase activity measured by IVIS in Panel A were determined by two-way ANOVA. Changes in luciferase activity were significantly altered in EGR4 knockout mice (P < 0.0112).",
    "ncbi_link": "GFP: 
luciferase: 
EGR4: 13656"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. All lung tumors were isolated from both WT and EGR4KO mice along with spleens and analysed for CD45+ cells. WT lung tumors were 5.407 ± 1.843% CD45+, while EGR4KO mice were 12.445 ± 2.239% CD45+. WT spleens were 83.92 ± 3.344% CD45+, while EGR4KO mice were 95.13 ± 1.856% CD45+. Relative distributions of T and myeloid cells within the CD45+ populations were determined by flow cytometric analysis. (E,F) Distributions of T and myeloid cells found within lung tumors (E) vs. the spleen (F).",
    "ncbi_link": "GFP: 
luciferase: 
EGR4: 13656"
  },
  {
    "caption": "B16N melanoma cells stably expressing GFP-luciferase were injected into syngeneic WT and EGR4-/- mice by tail vein injection. All lung tumors were isolated from both WT and EGR4KO mice along with spleens and analysed for CD45+ cells. (G) Representative FACS plots depicting gating strategies for defining Treg cell populations in Panels E and F",
    "ncbi_link": "GFP: 
luciferase: 
EGR4: 13656"
  },
  {
    "caption": "Tumors collected and analysed for exhaustion/anergy. Cells were collected and enriched for the immune cell population by Ficoll-Hypaque. WT cells were 36.9 ± 4.68% Thy1.2+, EGR4KO cells were 48.0 ± 0.58% Thy1.2+. (A) CD4+ and CD8+ T cells were stimulated in vitro with ionomycin/PMA before intracellular staining for IFNγ, IL-17 and IL-9 and FACS analysis.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "Tumors collected and analysed for exhaustion/anergy. Cells were collected and enriched for the immune cell population by Ficoll-Hypaque. WT cells were 36.9 ± 4.68% Thy1.2+, EGR4KO cells were 48.0 ± 0.58% Thy1.2+. (B,C) Representative FACS plots depicting gating strategies for defining cytokine expression in panels A to D",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "Tumors collected and analysed for exhaustion/anergy. Cells were collected and enriched for the immune cell population by Ficoll-Hypaque. WT cells were 36.9 ± 4.68% Thy1.2+, EGR4KO cells were 48.0 ± 0.58% Thy1.2+. CD4+ and CD8+ T cells were stained with CD44, CD73, FR4 and PD1 to monitor the formation of anergic/exhausted T cells. (D) Percentages of each population.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "Tumors collected and analysed for exhaustion/anergy. Cells were collected and enriched for the immune cell population by Ficoll-Hypaque. WT cells were 36.9 ± 4.68% Thy1.2+, EGR4KO cells were 48.0 ± 0.58% Thy1.2+. CD4+ and CD8+ T cells were stained with CD44, CD73, FR4 and PD1 to monitor the formation of anergic/exhausted T cells. (E) Gating strategies.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "Tumors collected and analysed for exhaustion/anergy. Cells were collected and enriched for the immune cell population by Ficoll-Hypaque. WT cells were 36.9 ± 4.68% Thy1.2+, EGR4KO cells were 48.0 ± 0.58% Thy1.2+. (F) FR4 and PD1 levels in WT vs. EGR4-/- T cells.",
    "ncbi_link": "EGR4: 13656"
  },
  {
    "caption": "BMDMs  were treated with  palmitic acid  (0, 100 μM, or 200 μM) for 12 h and transfected with HT-DNA  (2 μg/mL) for 6 h before  RT-qPCR analysis of Ifna4  (K), IFNb1  (L) expression. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.005; ***, P˂0.001",
    "ncbi_link": "Ifna4: 15967
IFNb1: 15977"
  },
  {
    "caption": "BMDMs  were treated with  palmitic acid (0, 100 μM, or 200 μM) for 12 h and transfected with HT-DNA (2 μg/mL) for 6 h before RT-qPCR analysis of , Cxcl10  (M) and Rantes  (N) expression. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.005; ***, P˂0.001",
    "ncbi_link": "Rantes: 20304
Cxcl10: 15945"
  },
  {
    "caption": "(A) Acyl-RAC assay  of HEK293T  cells transfected with Flag-cGAS  24 h after transfection with the indicated shRNA. (B) Quantification of palmitoylation  levels of Flag-cGAS  in (A). Data information:",
    "ncbi_link": "Flag: 
cGAS: 115004"
  },
  {
    "caption": "(D) HEK293T  cells were transfected with HA-cGAS  (WT or C474S mutant) (200 ng), Flag-STING  (200 ng) and Myc-ZDHHC18  (200 ng) expression plasmids for 24 h before  luciferase reporter assays. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; **, P˂0.005; ***, P˂0.001 (D",
    "ncbi_link": "Flag: 
HA: 
Myc: 
cGAS: 115004
STING: 340061
ZDHHC18: 84243"
  },
  {
    "caption": "(H) Immunoprecipitation  (with an anti-Flag  antibody) and immunoblot  analysis of HEK293T  cells transfected with plasmids encoding HA-cGAS  and Flag-ZDHHC18  truncations or GFP  for 24 h. Data information: WCL: whole-cell lysate; IP: immunoprecipitation; FL: full length",
    "ncbi_link": "Flag: 
GFP: 
HA: 
cGAS: 115004
ZDHHC18: 84243"
  },
  {
    "caption": "(J) Immunoprecipitation  (with an anti-Flag  antibody) and immunoblot  analysis of HEK293T  cells transfected with plasmids encoding HA-ZDHHC18  and Flag-cGAS truncates or GFP  for 24 h. Data information: WCL: whole-cell lysate",
    "ncbi_link": "Flag: 
GFP: 
HA: 
cGAS: 115004
ZDHHC18: 84243"
  },
  {
    "caption": "(H)  Confocal microscopy of BMDMs  (Zdhhc18+/+ or Zdhhc18−/−) transfected with FITC-conjugated ISD  for 6 h (left). Scale bar: 20 μm.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "(D) Immunoprecipitation  (with an anti-Flag  antibody) and immunoblot  analysis of HEK293T  cells transfected with plasmids encoding Flag-cGAS, HA-cGAS, and Myc-ZDHHC18  (WT or CS mutant) for 24 h. Data information: WCL: whole-cell lysate; IP: immunoprecipitation; Data are representative of at least two independent experiments.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
cGAS: 115004
ZDHHC18: 84243"
  },
  {
    "caption": "(H) Immunoprecipitation  (with an anti-Flag  antibody) and immunoblot  analysis of HEK293T  cells transfected with Flag-cGAS  and HA-cGAS   (WT, C405S, C409S and C474S) expression plasmids. Data information: WCL: whole-cell lysate; IP: immunoprecipitation  Data are representative of at least two independent experiments.",
    "ncbi_link": "Flag: 
cGAS: 115004"
  },
  {
    "caption": "(A) HEK293T  cells (5×105) were transfected with HA-cGAS  (200 ng), Flag-STING  (200 ng) and Myc-ZDHHC18  (WT or CS mutant) expression plasmids (0, 50, 100, or 200 ng) for 24 h before  luciferase reporter assays were conducted. Data information: ZDHHC18(CS): a catalytic mutant with a cysteine-to-serine  substitution in the DHHC motif of ZDHHC18  All data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.01; ***, P˂0.001 (A",
    "ncbi_link": "Flag: 
HA: 
Myc: 
cGAS: 115004
STING: 340061
ZDHHC18: 84243"
  },
  {
    "caption": "(B) HEK293T  cells (1×106) were transfected with HA-cGAS  (500 ng), Flag-STING  (500 ng) and Myc-ZDHHC18  (500 ng) expression plasmids for 24 h. TBK1 phosphorylation  was detected by immunoblotting. Data information: ZDHHC18(CS): a catalytic mutant with a cysteine-to-serine  substitution in the DHHC motif of ZDHHC18",
    "ncbi_link": "Flag: 
HA: 
Myc: 
cGAS: 115004
STING: 340061
ZDHHC18: 84243"
  },
  {
    "caption": "(C and D) HEK293T  cells were transfected with the indicated plasmids, and the amount of cGAMP  in the lysates was quantified by  LC-MS/MS. Data information: ZDHHC18(CS): a catalytic mutant with a cysteine-to-serine  substitution in the DHHC motif of ZDHHC18; LC-MS/MS: liquid chromatography-tandem mass spectrometry;",
    "ncbi_link": "ZDHHC18: 84243"
  },
  {
    "caption": "L929  cells stably transfected with control shRNA or ZDHHC18   shRNA The knockdown efficiency of ZDHHC18   is shown by RT-qPCR  (E) results. Data information: NC: negative control. All data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.01; ***, P˂0.001",
    "ncbi_link": "ZDHHC18: 503610"
  },
  {
    "caption": "L929  cells stably transfected with control shRNA or ZDHHC18  shRNA efficiency of ZDHHC18  is shown by  western blotting (F) results. Data information: NC: negative control.",
    "ncbi_link": "ZDHHC18: 503610"
  },
  {
    "caption": "L929  cells stably transfected with control shRNA or ZDHHC18  shRNA were transfected with HT-DNA (2 μg/mL) for the indicated times  before RT-qPCR  analysis of Ifna4  (G), expression. Data information:  HT-DNA: herring testis DNA; NC: negative control. All data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.01; ***, P˂0.001",
    "ncbi_link": "Ifna4: 15967
ZDHHC18: 503610"
  },
  {
    "caption": "L929  cells stably transfected with control shRNA or ZDHHC18  shRNA were transfected with HT-DNA (2 μg/mL) for the indicated times  before RT-qPCR analysis of IFNb1  (H), and Cxcl10  (I) expression. Data information: HT-DNA: herring testis DNA; NC: negative control. All data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; ns, not significant; **, P˂0.01; ***, P˂0.001",
    "ncbi_link": "Cxcl10: 15945
IFNb1: 15977
ZDHHC18: 503610"
  },
  {
    "caption": "(J) L929  cells stably transfected with control shRNA or ZDHHC18  shRNA were transfected with HT-DNA  (2 μg/mL) for the indicated times   before immunoblotting  analysis with the indicated antibodies. Data information: HT-DNA: herring testis DNA; NC: negative control.",
    "ncbi_link": "ZDHHC18: 503610"
  },
  {
    "caption": "(A) Survival  analysis of Zdhhc18+/+ and Zdhhc18-/- mice  (n = 8 each, 6-8 weeks old) intranasally injected with VACV  (5 × 107 PFU per mouse) and monitored daily for survival  for 13 days using  Kaplan-Meier curves and a log-rank (Mantel-Cox) test. ***, P˂0.001.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "(B) Representative photomicrographs  of H&E-stained liver  and kidney  tissue sections from mice  (Zdhhc18+/+ or Zdhhc18-/-) intravenously injected with HSV-1-FS (5 × 107 PFU per mouse) or not after 2 days. Scale bars: 100 μm (liver), 200 μm (kidney). Data information: PFU: plaque-forming units; H&E: hematoxylin-eosin. Data are representative of at least two independent experiments.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "(C BMDMs  (Zdhhc18+/+ or Zdhhc18-/-) were infected with  HSV-1  (MOI=2) for 8 h, and viral titers in the supernatants were quantified by plaque assay. Data information: Data are representative of at least two independent experiments.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "D) BMDMs  (Zdhhc18+/+ or Zdhhc18-/-) were infected with HSV-1 (MOI=2) for 8 h, and  viral titers in the supernatants were quantified by plaque assay. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; Ns: no significance; *, P˂0.05; **, P˂0.01; ****, P˂0.0001 (D",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "F) Microscopy of BMDMs  (Zdhhc18+/+ or Zdhhc18-/-) infected with GFP-HSV-1 (MOI=1) for 10 h. Scale bar: 200 μm. Data information: Data are representative of at least two independent experiments.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "(G) MEFs (Zdhhc18+/+ or Zdhhc18-/-) were infected with VACV  (1:200) for the indicated times  before immunoblot  analysis.",
    "ncbi_link": "Zdhhc18: 503610"
  },
  {
    "caption": "(H and I) MEFs  (Zdhhc18+/+ or Zdhhc18-/-) were infected with VACV  (1:200) for the indicated times before RT-qPCR analysis of Cxcl10  (H) and Ifnb1  (I) expression. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; Ns: no significance; *, P˂0.05; **, P˂0.01; ****, P˂0.0001",
    "ncbi_link": "Cxcl10: 15945
Ifnb1: 15977
Zdhhc18: 503610"
  },
  {
    "caption": "(J) PBMCs  from healthy people were transfected with scrambled siRNA or ZDHHC18  siRNA (cocktail) for 48 h and then infected with VACV  (1:200) for the indicated times before RT-qPCR analysis of IFNB1 expression. Data information: Data are representative of at least two independent experiments. Mean ± SEM from triplicates of technical replicates, unpaired t test; Ns: no significance; *, P˂0.05; **, P˂0.01; ****, P˂0.0001",
    "ncbi_link": "IFNB1: 3456
ZDHHC18: 84243"
  },
  {
    "caption": "A. qPCR analysis of Ahr expression in B cell subsets purified from C57Bl/6 mice. Ahr expression was normalized to Hprt1. n = 3-5 independent experiments; mean ± SD.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "B. qPCR analysis of Ahr expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for 4h as indicated. Ahr expression was normalized to Hprt1. Ahr expression among groups was normalized to Medium. n = 4 independent experiments; mean ± SEM; one-way ANOVA, Dunnett's multiple comparison test.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "C. qPCR analysis of Ahr expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for 4h with 20 ng/ml IL-4 and/or 10 μg/ml α-IgM. Ahr expression was normalized to Hprt1. Ahr expression among groups was normalized to Medium. n = 3 independent experiments; mean ± SEM; one-way ANOVA, Tukey's multiple comparison test.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "F. qPCR analysis of Ahr expression in purified splenic B cell subsets isolated from C57Bl/6 mice and cultured as indicated for 4h. Ahr expression was normalized to Hprt1. n = 2 independent experiments; mean ± range.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "G. qPCR analysis of Ahr expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for the indicated time points with 20 ng/ml IL-4 and/or 10 μg/ml α-IgM. Ahr expression was normalized to Hprt1. Ahr expression among groups was normalized to Medium. n = 5 independent experiments; mean ± SEM; one-way ANOVA, Dunnett's multiple comparison test.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "B. qPCR analysis of Cyp1a1 expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for 24h as indicated. Cyp1a1 expression was normalized to Hprt1. Cyp1a1 expression among groups was normalized to Medium DMSO. n = 2 independent experiments; mean ± range.",
    "ncbi_link": "Hprt1: 
Cyp1a1: 13076"
  },
  {
    "caption": "C. Flow cytometry analysis of Cyp1a1 expression, reported by eYFP, in splenic CD19+ cells isolated from Cyp1a1Cre R26R eYFP mice and cultured for 72h as indicated. Representative data of n = 3 independent experiments.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "D. qPCR analysis of Cyp1a1 expression in purified splenic B cell subsets isolated from C57Bl/6 mice and cultured as indicated for 24h. Cyp1a1 expression was normalized to Hprt1. n = 2 independent experiments; mean ± range.",
    "ncbi_link": "Hprt1: 
Cyp1a1: 13076"
  },
  {
    "caption": "A. Flow cytometry analysis of CTV dilution in splenic CD19+ cells sorted from non-immune Ahrfl/+mb1Cre+ (Ahr+/- B cells, solid grey) and Ahrfl/-mb1Cre+ (Ahr-/- B cells, black) mice stimulated for 72h as indicated. Treatment of Ahr+/- CD19+ cells with CH223191 is indicated in red. Representative data of n = 4-5 independent experiments.B-D. Flow cytometry analysis of expansion index (B), % of divided cells (C) and replication index (D) of splenic CD19+ cells sorted from non-immune Ahrfl/+mb1Cre+ (black) and Ahrfl/-mb1Cre+ (white) mice stimulated for 72h as indicated. Treatment of Ahr+/- CD19+ cells with CH223191 is indicated in red. n = 4-5 independent experiments; mean ± SEM; 2-way ANOVA, Sidak's multiple comparison test.",
    "ncbi_link": "Cre: 
Ahr: 11622
mb1: 12518"
  },
  {
    "caption": "E. Flow cytometry analysis of cell cycle distribution of splenic CD19+ cells purified from non-immune Ahrfl/+mb1Cre+ (black) and Ahrfl/-mb1Cre+ (white) mice stimulated for 48h with 5 µg/ml α-IgM. Data representative of n = 2 independent experiments; lines indicate mean; 2-way ANOVA, Sidak's multiple comparison test.",
    "ncbi_link": "Cre: 
Ahr: 11622
mb1: 12518"
  },
  {
    "caption": "A, B. Flow cytometry analysis of distribution of CD45.1+ and CD45.2+ cells in indicated cell subsets purified from bone marrow (A) and lymph node (B) of sub lethally-irradiated Rag1-/- mice 8 weeks after reconstitution with equal numbers of bone marrow cells from Ahr+/+ (CD45.1+) and Ahr-/- (CD45.2+) mice. Dashed lines indicate 50% level. Representative data of n = 2 independent experiments; two-tailed paired t test.",
    "ncbi_link": "Ahr: 11622
Rag1: 19373"
  },
  {
    "caption": "E. Flow cytometry analysis of distribution of Ahr+/+ CD45.1+CD45.2+ (black) and Ahr-/- CD45.2+ (white) cells harvested from host mice. Indicated distribution is quantified relative to transferred cells. X symbols indicate SRBC-mock-treated control. Dashed line indicates 50% threshold. Representative data of n = 3 independent experiments; two-tailed paired t test.",
    "ncbi_link": "Ahr: 11622"
  },
  {
    "caption": "F, G. Flow cytometry analysis of distribution (F) and cell numbers (G) of IgG1+ and IgG1- HEL3x-binding Ahr+/+ CD45.1+CD45.2+ (black) and Ahr-/- CD45.2+ (white) cells harvested from host mice. Representative data of n = 2 independent experiments; two-tailed paired t test.",
    "ncbi_link": "Ahr: 11622"
  },
  {
    "caption": "A, B. Tables showing top 20 down-regulated (A) genes in Ahr-/- B cells as compared to Ahr+/+ cells, after analysis by RNA sequencing. B cells were activated with 10 µg/ml α-IgM + 20 ng/ml IL-4 for 8h; 250 nM FICZ was added to the culture during the last 4h. The average read counts are directly proportional to the extent of expression of a given gene in Ahr+/+ or Ahr-/- cells. Data from n = 3 mice per group. Average read counts for the housekeeping gene Hprt1 in both Ahr+/+ and Ahr-/- B cells are indicated below the table in figure 6A.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "A, B. Tables showing top up-regulated (B) genes in Ahr-/- B cells as compared to Ahr+/+ cells, after analysis by RNA sequencing. B cells were activated with 10 µg/ml α-IgM + 20 ng/ml IL-4 for 8h; 250 nM FICZ was added to the culture during the last 4h. The average read counts are directly proportional to the extent of expression of a given gene in Ahr+/+ or Ahr-/- cells. Data from n = 3 mice per group. Average read counts for the housekeeping gene Hprt1 in both Ahr+/+ and Ahr-/- B cells are indicated below the table in figure 6A.",
    "ncbi_link": "Hprt1: 
Ahr: 11622"
  },
  {
    "caption": "C. qPCR analysis of Ccno expression in splenic CD19+ cells isolated from non-immune Ahrfl/+mb1Cre+ (Ahr+/- B cells, black) and Ahrfl/-mb1Cre+ (Ahr-/- B cells, white) mice, stimulated with 10 µg/ml anti-IgM for the indicated time points. Ccno expression was normalized to Hprt1. n = 3 independent experiments; mean ± SEM; two-way ANOVA, Sidak's multiple comparison test.",
    "ncbi_link": "Cre: 
Ahr: 11622
Ccno: 218630
mb1: 12518"
  },
  {
    "caption": "D. qPCR analysis of Ccno expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for 8h with 20 ng/ml IL-4 and/or 10 μg/ml α-IgM. Ccno expression was normalized to Hprt1. n = 3 independent experiments; mean ± SEM; one-way ANOVA, Tukey's multiple comparison test.",
    "ncbi_link": "Hprt1: 
Ccno: 218630"
  },
  {
    "caption": "E. qPCR analysis of Ccno expression in splenic CD19+ cells isolated from C57Bl/6 mice and cultured for the indicated time points with 20 ng/ml IL-4 and/or 10 μg/ml α-IgM in presence or absence of 250 nM FICZ or 1 μM 3-MC. Ccno expression was normalized to Hprt1. n = 3 independent experiments; mean ± SEM; one-way ANOVA, Tukey's multiple comparison test.",
    "ncbi_link": "Hprt1: 
Ccno: 218630"
  },
  {
    "caption": "F. Chromatin Immunoprecipitation (ChIP) analysis of AhR interaction with the Ccno promoter and an irrelevant region (-3.3 Kb from Ccno transcription starting site) in Ahr+/+ (black) and Ahr-/- (white) B cells 5h after activation with 10 µg/ml α-IgM + 20 ng/ml IL-4. 250 nM FICZ was added in the last hour of culture. Representative data of n = 2 independent experiments; mean ± SEM; two-way ANOVA, Sidak's multiple comparison test.",
    "ncbi_link": "Ahr: 11622
Ccno: 218630"
  },
  {
    "caption": "D: Co-immunoprecipitation  of TMBIM5 and LETM1  protein in tandem in the left 3 panels. The input represents the mitochondrial  crudely isolated from HEK293  cells and was used as input for the co-IP, LETM1  was immunoprecipitated  (left panel, IP: LETM1) using a LETM1  monoclonal antibody and Protein G magnetic beads (ProtG). ProtG   beads alone were used as a negative control for binding, immunoprecipitates  were immunoblotted  (IB) for the indicated proteins to demonstrate interaction. 10% of the input was used for immunoblotting. Prohibitin  (PHB) was used as a control to illustrate no nonspecific binding  of inner mitochondrial membrane proteins complexes. The middle and right panel of the coIPs  illustrates the converse experiment, in the middle in  TMBIM5WT and right TMBIMKO, using TMBIM5  as bait (right panel, IP: TMBIM5). The last two right panels show blots  from BN-PAGE conducted in TMBIM5WT and KO.",
    "ncbi_link": "TMBIM: 27069
TMBIM5: 27069"
  },
  {
    "caption": "E: Isolated mitochondria  from three independent replicates of HEK293 TMBIM5WT and TMBIM5KO1 and KO2 were analyzed by immunoblotting  using the indicated antibodies, HSP60  and TOM40  served as mitochondrial  loading controls. F: Densitometric  analysis of the bands in (E) normalized to loading control, bar graph of three individual experiments (biological replicates), mean ± SD, One-way ANOVA with Bonferroni's multiple comparisons test performed against TMBIM5WT *p<0.05, **p<0.008, Two-way ANOVA with Bonferroni's multiple comparisons test performed for the OPA1  statistics against TMBIM5WT, ***p=0.0009, ****p<0.0001.",
    "ncbi_link": "TMBIM5: 27069"
  },
  {
    "caption": "(E) WB analysis of NEDD4L, EZH2  and EZH1 expression in the EZH2-specific siRNA (siEZH2)- or negative control siRNA (siNC)-transfected NHEKs with  IMQ stimulation. Data information: Data are shown as the mean ± s.e.m., and are representative of three independent experiments Scale bar, 200 μm (100×) or 50 μm (400×).",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": "NEDD4L was knocked out by the CRISPR Cas9 method in NHEKs. WT and NEDD4L KO NHEKs were  infected with lentivirus overexpressing NEDD4L-WT or NEDD4L-C943S mutants. cell signaling pathway activation  induced by IL-6 were detected by WB analyses Data information: Data are shown as the mean ± s.e.m., and are representative of three independent experiments",
    "ncbi_link": "Cas9: 57852564
NEDD4L: 23327"
  },
  {
    "caption": "(G, H) Primary keratinocytes were separated from the WT and Nedd4l KO mice. (G) WB analysis of the protein expression in IL-6-induced cell signaling pathway activation. (H) WB analysis  of the proteins in the  IL-6 signaling pathway. Data information: Data are shown as the mean ± s.e.m., and are representative of three independent experiments",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "Six- to eight-weeks old WT and Nedd4l  cKO mice were treated with IMQ for 6 consecutive days and at the beginning of the treatment, the mice were injected  intra-epidermally with 10 μg anti-GP130 antibody or with same dosage of isotype on every other day. Representative images of Ki67 staining in back tissues are on the left. The number of Ki67-positive cells per HPF is shown on the right. Data information: Data are shown as mean ± s.e.m., and are representative of two independent experiments. Scale bar, 200 μm (100×) or 50 μm (400×). Significant differences were tested using a two-tailed Student's t test C, control, n=5, IMQ, n=6. * P＜0.05, ** P＜0.01, *** P＜0.001. NS, no significance.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "Six- to eight-weeks old WT and Nedd4l  cKO mice were treated with IMQ for 6 consecutive days and at the beginning of the treatment, the mice were injected intra-epidermally with 10 μg anti-GP130 antibody or with same dosage of isotype on every other day. Keratinocyte proliferation associated genes in the skin tissues  are detected using real-time PCR analysis. Data information: Data are shown as mean ± s.e.m., and are representative of two independent experiments. Scale bar, 200 μm (100×) or 50 μm (400×). Significant differences were tested using a two-tailed Student's t test D, control, n=3, IMQ, n=6. * P＜0.05, ** P＜0.01, *** P＜0.001. NS, no significance.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "(F) Full length Flag-GP130,  GP130-aa 616-918, GP130-aa 616-889, GP130-aa 616-764, GP130-aa 616-734 were transfected with Myc-NEDD4L into  HEK293T cells, and whole cell lysates were co-IP with ANTI-FLAG M2 magnetic beads, followed by WB with anti-Flag or anti-Myc antibodies.",
    "ncbi_link": "Flag: 
GP130: 3572
NEDD4L: 83814"
  },
  {
    "caption": "(C) WT or  NEDD4L KO NHEK  cells was infected with  lentivirus that overexpress NEDD4L-WT, NEDD4L WW domain truncated mutant (NEDD4L-ΔWW) or its enzymatic activity mutant (NEDD4L-C943S), the cells were followed by denaturation-IP with anti-GP130 antibody and WB analysis with anti-Ub antibodies.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(E) WB analysis of the polyubiquitination of GP130 in HEK293T cells co-transfected with full length Myc-NEDD4L, HA-Ub and Flag-GP130 or its lysine mutants (K-R) in the intracellular domain, followed by denaturation-IP with ANTI-FLAG M2 magnetic beads and WB analysis with anti-HA antibodies.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
GP130: 3572
NEDD4L: 83814
Ub: 10537///7316///7314"
  },
  {
    "caption": "(a) Expression of ATG16L1 in a set of different tissues as detected by RT-PCR (IEC, intestinal epithelial cells). The corresponding β-actin control (with a 518-bp amplicon size) is given below.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "b) Amounts of ATG16L1 in colonic mucosal biopsy specimens. Proteins (15 μg) from rectal mucosal biopsies of Crohn disease patients and normal controls (N) were separated by denaturing SDS-PAGE, transferred onto polyvinylidine fluoride (PVDF) membranes and probed for the presence of ATG16L1 using a specific primary antibody and horseradish peroxidase-coupled secondary antibody. The abundant 68.2-kDa band corresponds to the predicted molecular weight of the isoform encoded by GenBank AY398617 (UniProt accession number Q676U5). This major protein form was used for three-dimensional modeling of the ATG16L1 protein (Fig. 2). The 48.5-kDa band corresponds to GenBank EF079890, which contains exon 9 (harboring rs2241880) in the same reading frame as the major form.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(c-i) Representative immunohistochemistry results (out of six normal controls and six individuals with Crohn disease) from colonic mucosal tissue samples from normal controls for genotype AA (c) and GG (f) and individuals with Crohn disease for genotype AA (d) and GG (g) are shown to demonstrate the cellular localization of the ATG16L1 protein. Cellular expression patterns in mononuclear cells (h) and intestinal epithelial cells (i) of a Crohn disease sample (rs2241880AA) are shown at higher magnification. e shows a Crohn disease sample without the primary antibody, used as a control. Bar represents 10 μm in c-g.",
    "ncbi_link": "rs2241880: 55054"
  },
  {
    "caption": "The 32 β-strands forming an eight-bladed β-propeller are numbered as in Supplementary Note. The location of the variant amino acid T300A in strand β3, corresponding to rs2241880, is marked in yellow.",
    "ncbi_link": "rs2241880: 55054"
  },
  {
    "caption": "Immunoblot (IB) analyses of the levels of β-catenin and RAS in DLD1, WT-HCT116, MT-HCT116, HepG2, and SW48 cells transfected with Myc-axin for 36 hr",
    "ncbi_link": "Myc: 
axin: 8313///8312"
  },
  {
    "caption": "Effects of β-catenin knock-down on polyubiquitination-dependent degradation of RAS. IB analyses of MT-HCT116 cells transfected with control or two independent β-catenin siRNAs for 48 hr",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "Polyubiquitination assays of MT-HCT116 cells cotransfected with two independent β-catenin siRNAs and HA-ubiquitin (Ub) for 72 hr in the presence of the proteasomal inhibitor MG132, and WCLs were immunoprecipitated with an anti-pan-RAS antibody",
    "ncbi_link": "Ub: 
ubiquitin: 
β-catenin: 1499"
  },
  {
    "caption": "IB analyses of HEK293 cells transfected with WT- or S33Y-Flag-β-catenin with or without HA-GSK3β for 36 hr",
    "ncbi_link": "β-catenin: 1499
GSK3β: 2932"
  },
  {
    "caption": "IB analyses of HEK293 cells transfected with β-catenin siRNA or control siRNA for 48 h and then treated with L-cell-conditioned medium (L-CM) or Wnt3a-CM for 8 hr",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "Effects of KYA1797K or XAV939 on degradation of β-catenin and RAS in isogenic HCT116 cells harboring WT- or MT-CTNNB1. IB analyses of β-catenin and RAS levels in WT- or MT-HCT116 cells treated with 5 or 20 µM of KYA1797K or XAV939 for 24 hr",
    "ncbi_link": "CTNNB1: 1499"
  },
  {
    "caption": "In vitro pulldown analyses to identify β-catenin binding region of RAS. Upper panel: Schematic of the HRAS full-length (FL) or two deletion mutants. Lower panel: Purified GST-HRAS-FL, -ΔHVR, or -Δ131-165 proteins were pulled-down with purified His-β-catenin-FL protein and subjected to IB analyses",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "IB analyses of IP with FLAG antibody in WCLs of HEK293 cells cotransfected with FLAG-β-catenin and Myc-HRAS-FL, -ΔHVR, or -Δ131-165 for 32 hr",
    "ncbi_link": "β-catenin: 1499
HRAS: 3265"
  },
  {
    "caption": "IB analyses of IP with FLAG antibody in WCLs of HEK293 cells cotransfected with FLAG-β-catenin and Myc-HRAS-WT, -2A, or -2E for 32 hr",
    "ncbi_link": "β-catenin: 1499
HRAS: 3265"
  },
  {
    "caption": "Upper panel: Schematic of the β-catenin-FL or two deletion mutants. Lower panel: Purified His-β-catenin-FL, ΔN86, or ΔC110 proteins were pull-down with purified GST-HRAS-FL protein and subjected to IB analyses",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "IB analyses of IP with Myc antibody with WCLs of HEK293 cells cotransfected with Myc-HRAS and GFP-β-catenin-FL, -ΔN86, or -ΔC110 for 32 hr",
    "ncbi_link": "β-catenin: 1499
HRAS: 3265"
  },
  {
    "caption": "IB analyses were performed to detect β-catenin and pan-RAS in DLD1 cells cotransfected with FLAG-β-catenin-WT or -MT and Myc-KRAS-WT or -2A for 24 hr and then treated or transfected with 20 µM of KYA1797K or HA-GSK3β for 24 hr, respectively",
    "ncbi_link": "β-catenin: 1499
GSK3β: 2932
KRAS: 3845"
  },
  {
    "caption": "IB analyses to determine the interaction between β-catenin and BBR peptide by in vitro pull-down assays using purified His-β-catenin and GST-BBR proteins",
    "ncbi_link": "BBR: 
β-catenin: 1499"
  },
  {
    "caption": "IB analyses of IP with FLAG antibody and WCLs from HEK293 cells cotransfected with FLAG-β-catenin and GFP-BBR or -Mock in the presence of proteasome inhibitor, ALLN, for 24 hr",
    "ncbi_link": "β-catenin: 1499
BBR: 3845"
  },
  {
    "caption": "Effects of BBR overexpression on KYA1797K-induced RAS degradation. I analyses to detect levels of RAS in MT-HCT116 cells transfected with GFP-Mock or -BBR for 24 hr and then treated with 20 µM of KYA1797K for 24 hr",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Effects of BBR overexpression on KYA1797K-induced RAS degradation ICC (D; Scale bars, 10 µm) analyses to detect levels of RAS in MT-HCT116 cells transfected with GFP-Mock or -BBR for 24 hr and then treated with 20 µM of KYA1797K for 24 hr",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "MT-HCT116 cells were cotransfected with GFP-Mock or -BBR and FLAG-Ub for 24 hr and then treated with 20 µM of KYA1797K in the presence of MG132 for 8 hr, and WCLs were immunoprecipitated with pan-RAS antibody",
    "ncbi_link": "Ub: 
BBR: 3845"
  },
  {
    "caption": "IB analyses of IP with β-catenin antibody in MT-HCT116 cells transfected with GFP-BBR-WT, -2E, or GFP-Mock in the presence of ALLN for 24 hr",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "IB analyses of MT-HCT116 cells transfected with GFP-Mock, -BBR-WT, or -BBR-2E for 24 hr and then treated with 20 µM of KYA1797K for 24 hr",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "MT-HCT116 cells were transfected with GFP-Mock, -BBR-WT, or -BBR-2E together with FLAG-Ub with or without 20 µM of KYA1797K for 24 hr and MG132 was treated for 8 hr before harvesting cells. WCLs were immunoprecipitated with pan-RAS antibody and subjected to IB analyses",
    "ncbi_link": "Ub: 
BBR: 3845"
  },
  {
    "caption": "Effects of KYA1797K and PTD-BBR on RAS degradation IB assay of MT-HCT116 or SW48 cells treated with indicated conditions for 24 and 96 hr, respectively",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Effects of KYA1797K and PTD-BBR o cell growth MTT assays of MT-HCT116 or SW48 cells treated with indicated conditions for 24 and 96 hr, respectively. Data are presented as the mean ± SD (n = 3)",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Effects of overexpression of GFP-BBR-WT or -2E mutant on KYA1797K-induced growth and transformation of CRC cells. MT-HCT116 or SW48 cells were transfected with GFP-BBR-WT, -2E, or GFP-Mock for 24 hr and then treated with KYA1797K via indicated conditions MTT assays were performed for measurements of cell growth",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Effects of overexpression of GFP-BBR-WT or -2E mutant on KYA1797K-induced growth and transformation of CRC cells. MT-HCT116 or SW48 cells were transfected with GFP-BBR-WT, -2E, or GFP-Mock for 24 hr and then treated with KYA1797K via indicated conditions foci formation assay were performed to detect cellular transformation",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Effects of cotreatments with KYA1797K and PTD-BBR on xenografted tumor growth. MT-HCT116 cells were subcutaneously injected in nude mice with subsequent i.p. injection of vehicle, 20 mg/kg of KYA1797K, or a cotreatment of PTD-BBR (25 mg/kg) and KYA1797K (20 mg/kg) for 20 d. Tumor volumes (upper panel) were measured every 4 days, and tumor weights (lower panel) were measured at the times of sacrifice. Data are presented as the mean ± SD (four mice per group)",
    "ncbi_link": "BBR: 3845"
  },
  {
    "caption": "Viability of single and double mutants of RNAPII and rad52Δ, mre11Δ and cdc44‐8. Tenfold serial dilutions of double mutants obtained by genetic crosses were tested for growth in plain SC medium or supplemented with 10 mM HU or 0.005% MMS.",
    "ncbi_link": "mre11: 855264
rad52: 854976
cdc44: 854392"
  },
  {
    "caption": "Tetrad analysis of rpb1‐S751F, rad52Δ and mre11Δ crosses. Δ indicates double mutants that fail to grow.",
    "ncbi_link": "mre11: 855264
rad52: 854976
rpb1: 851415"
  },
  {
    "caption": "Tetrad analysis of rpb1‐S751F crossed by pol32Δ and rad51Δ. Δ indicates triple mutants that fail to grow.",
    "ncbi_link": "pol32: 853500
rad51: 856831
rpb1: 851415"
  },
  {
    "caption": "HU and MMS sensitivity of different mutant combinations of rpb1‐1, rpb1‐S751F, pol32Δ and rad51Δ.",
    "ncbi_link": "pol32: 853500
rad51: 856831
rpb1: 851415"
  },
  {
    "caption": "Recombination frequencies between inverted repeats in WT and RNAPII mutants measured with the plasmid‐born pTINV system. Recombinants were selected as Leu+.",
    "ncbi_link": "Leu: 850342"
  },
  {
    "caption": "Recombination frequencies using the direct‐repeat chromosomal system leu2‐k::ADE2‐URA3::leu2‐k in WT and RNAPII mutants. Deletion events were detected and quantified in media containing 5‐fluorotic acid (FOA) and could be directly visualized as red sectors.",
    "ncbi_link": "ADE2: 854295
leu2: 850342
URA3: 856692"
  },
  {
    "caption": "Recombination frequencies between plasmid‐born direct repeats in WT and RNAPII mutants. The frequency of Leu+ recombination was determined in the systems L‐lacZ and GL‐lacZ. Recombination frequencies are plotted as a function of the transcription levels. Low transcription refers to the GL‐lacZ systems in strains cultured in 2% glucose; medium refers to L‐lacZ in 2% glucose, and high to GL‐lacZ in 2% galactose.",
    "ncbi_link": "lacZ: 
Leu: 850342"
  },
  {
    "caption": "Mitotic stability of centromeric plasmid pGAL‐lacZ in RNAPII mutants. Stability was analyzed in galactose after 23 generations. A small diagram of each system (not drawn to scale) is shown.",
    "ncbi_link": "lacZ: "
  },
  {
    "caption": "Recombination frequencies measured with the pTINV system in WT, rpb1‐1, mre11Δ and rpb1‐1 mre11Δ.",
    "ncbi_link": "mre11: 855264
rpb1: 851415"
  },
  {
    "caption": "Rad52 focus formation in asynchronously growing cells expressing normal or high levels of RNH1.",
    "ncbi_link": "RNH1: 855274"
  },
  {
    "caption": "Slowdown of RF progression through a chromosomal region. 2D gel electrophoresis of replication intermediates of 4.3‐kb PstI DNA fragments from WT and RNAPII mutants in the presence of 40 mM HU at different times after G1 release. A black arrow indicates accumulation of long Y molecules, and a white one indicates the specific accumulation of X molecules.",
    "ncbi_link": "PstI: 851625"
  },
  {
    "caption": "Analysis of replication by BrdU incorporation. Cells were synchronized in G1 with α‐factor and released in the presence of BrdU. Samples were taken at the indicated times and processed to measure BrdU incorporation by ChIP analysis. Replication was analyzed in two DNA regions, one covering the early origin ARS508 and the SPF1 gene and the other the late origin ARS603 and the YFL034W gene.",
    "ncbi_link": "ARS508: 
ARS603: 
YFL034W: 850510
SPF1: 856681"
  },
  {
    "caption": "Dephosphorylation of Rad53 after exposure to HU. WT, rpb1‐1 and rpb1‐S751F cells were synchronized in G1 with α‐factor. After G1 release, cells were exposed to 100 mM HU for 1 h, washed to remove HU and cultured in HU‐free medium for the indicated periods. Western blot against Rad53, signal quantification (ratio Rad53‐P/total Rad53 protein) and FACS profiles are shown.",
    "ncbi_link": "rpb1: 851415"
  },
  {
    "caption": "DNA repair of MMS damage. Chromosome VII species revealed by hybridization with ADE5,7 probes in pulsed‐field gel electrophoresis (PFGE). Asynchronously growing WT and rpb1 cells were exposed to 0.1% MMS for 30 min, washed to remove MMS and cultured in MMS‐free medium for the indicated periods to allow repair. Repair was calculated as the percentage of FLC appearing after MMS treatment. The FLC signal was quantified with respect to the total signal of each lane. Data show the mean and SD of 3 independent experiments. NLC, nonlinear chromosome. FLC, full‐length linear chromosome. CF, chromosome fragment resulting from DNA breaks.",
    "ncbi_link": "rpb1: 851415"
  },
  {
    "caption": "Retention of RNAPII in the actively transcribed PMA1 gene in RNAPII mutants. ChIP analysis of RNAPII in asynchronously growing WT, rpb1‐1, rpb1‐S751F, rpb2‐10 and rpb9Δ cells at the PMA1 gene. The scheme of the gene and the PCR‐amplified fragments are shown. Recruitment values were calculated from the amount of DNA present in each region, normalizing IP/input ratios, and relative to the amount of DNA of the intergenic region. Error bars indicate the standard deviation (SD).",
    "ncbi_link": "PMA1: 852876
rpb2: 854322
rpb9: 852810
rpb1: 851415"
  },
  {
    "caption": "Northern blot analysis of the expression of PMA1 gene. RNA was isolated from mid‐log phase cultures grown in YPD‐rich medium. As 32P‐labeled DNA probes, an internal 776‐bp PMA1 fragment and an internal 513‐bp SCR1 fragment obtained by PCR were used. Bars indicate the SD of 2 independent experiments.",
    "ncbi_link": "SCR1: 
PMA1: 852876"
  },
  {
    "caption": "Analysis of Rrm3 recruitment in WT and rpb1‐1. Rrm3 IP histogram bars in the y‐axis show the average signal log2 ratio of loci enriched in the immunoprecipitated fraction along the indicated regions in the x‐axis. When the ratio fulfills the P‐value criteria (P 0.01) it is shown in red.",
    "ncbi_link": "rpb1: 851415"
  },
  {
    "caption": "(A) UASp-GFP-mCherry-DrAtg8a/+;nosGAL4/+ flies conditioned on yeast paste had diffuse GFP-mCherry-DrAtg8a staining in midstage egg chambers. (B) Nondegenerating midstage egg chambers from starved flies contained autophagosomes (yellow) and autolysosomes (red). (C and D) Egg chambers early in the degeneration process showed follicle cells that take up portions of the nurse cell cytoplasm (C) followed by condensation and fragmentation of the nurse cell nuclei and further uptake of the nurse cell cytoplasm into follicle cells (D). (E) Late stage degenerating egg chambers lose all GFP staining and fluoresce red.",
    "ncbi_link": "Atg8a: 32001
nos: 42297"
  },
  {
    "caption": "(F) Fed Dcp-1Prev1/Dcp-1Prev1;UASp-GFP-mCherry-DrAtg8a/nosGAL4 flies showed diffuse GFP-mCherry-DrAtg8a staining in the germline. (G) Starved Dcp-1Prev1/Dcp-1Prev1;UASp-GFP-mCherry-DrAtg8a/nosGAL4 flies showed reduced autolysosomes in degenerating midstage egg chambers. (H and I) Fed flies overexpressing truncated Dcp-1 (tDcp-1) in the germline showed increased autophagosomes and autolysosomes in nondegenerating midstage egg chambers (H) and also contained degenerating midstage egg chambers that lose all GFP fluorescence and fluoresce red (I). Bars: (main images) 25 µm; (insets) 12.5 µm. Insets in A-I show diffuse cytoplasmic staining of Atg8a or autophagosomes and autolysosomes. (J and K) The percentages of autolysosomes (autolysosomes/total autophagic structures) were manually calculated in at least eight egg chambers for each genotype as indicated. Error bars represent the means ± SD. Statistical testing was performed using one-way ANOVA with a Dunnet post test (****, P < 0.0001) or a two-tailed Student's t test (**, P < 0.005).",
    "ncbi_link": "Atg8a: 32001
Dcp-1: 37729
nos: 42297"
  },
  {
    "caption": "(A) Drosophila S2 cells stably expressing GFP-RFP-Atg8a showed an increase in the percentage of cells containing two or more autolysosomes after starvation, which was blocked after Bafilomycin A1 (BafA1) treatment. At least 50 cells were manually quantitated in three independent experiments (n = 3). Statistical significance was determined using one-way ANOVA with a Dunnett post test (**, P < 0.01). (B) Representative images of S2-GFP-RFP-Atg8a cells after the indicated treatments.",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(C) S2-GFP-RFP-Atg8a cells were treated with dsRNAs and subjected to fed or starvation conditions as indicated. At least 50 cells were manually quantitated in three independent experiments (n = 3). Statistical significance was determined using one-way ANOVA with a Dunnett post test (**, P < 0.01; ***, P < 0.001; ****, P < 0.0001). (D) Representative images of S2-GFP-RFP-Atg8a cells after the indicated RNAi treatments. Error bars represent the means ± SD. Bars, 10 µm.",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(A) Nondegenerating midstage egg chambers from fed w1118flies showed Ref(2)P staining in follicle cells and nurse cells. (B) Starved w1118flies contained degenerating midstage egg chambers with reduced Ref(2)P.(D) Starved Atg7flies showed an accumulation of Ref(2)P in the follicle cells and nurse cells of degenerating midstage egg chambers. (E) Starved Dcp-1Prev1flies contained increased levels of Ref(2)P in degenerating midstage egg chambers.",
    "ncbi_link": "Atg7: 37141
Dcp-1: 37729"
  },
  {
    "caption": "(C) A representative Western blot of ovaries from w1118 and Atg7d77/d14 flies subjected to fed or starvation conditions for 4 d. Ref(2)P was detected by immunoblotting. Actin served as a loading control. Densitometry was performed to quantitate Ref(2)P protein levels relative to actin. Graph represents ± SD from five independent experiments (n = 5). Statistical significance was determined using a two-tailed Student's t test. *, P = 0.004 for fed samples; *, P = 0.008 for starved samples.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(F) A representative Western blot of ovaries from w1118 and Dcp-1Prev1 flies that were subjected to fed or starvation conditions for 4 d. Ref(2)P was detected by immunoblotting. Actin served as a loading control. Densitometry was performed to quantitate Ref(2)P protein levels relative to actin. Graph represents ± SD from five independent experiments (n = 5)",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(G) Control and Dcp-1 RNAi-treated cells were subjected to nutrient-rich or starvation conditions and stained with NAO. Mean fluorescence was measured by flow cytometry. Graph represents ± SEM of three independent experiments (n = 3).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(A) l(2)mbn cells were labeled with the ATPsyn-α, and mitochondrial morphology was scored as fragmented, normal, or elongated. (B) Cells were treated with control or Dcp-1 dsRNA and subjected to nutrient-rich media or 1 h of starvation. Quantifications represent the percentage of cells with elongated mitochondria divided by the total number of cells examined. At least 100 cells were examined manually in three independent experiments (n = 3). Error bars represent the mean ± SD. Statistical significance was determined using one-way ANOVA with a Bonferroni post test (*, P < 0.05; **, P < 0.01).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(C) Mitochondrial targeted GFP (mitoGFP) was expressed in the germline using the nosGAL4 driver. Staining shows mitoGFP, Armadillo, and DNA. (D) Mitochondria were scored as healthy (H), clustered (C), or elongated and overly connected (E). All of mitochondria from fed UASp-mitoGFP/+;nosGAL4/+ flies were scored as healthy. n = 15 egg chambers manually scored. (E) mitoGFP was expressed in Dcp-1Prev1 flies using the nosGAL4 driver. (F) 54% of egg chambers from UASp-mitoGFP/+;Dcp-1Prev1/Dcp-1Prev1;nosGAL4/+ flies contained elongated mitochondria, 39% contained mitochondria that were scored as healthy, and 7% contained clustered mitochondria. n = 28 egg chambers manually scored.",
    "ncbi_link": "Dcp-1: 37729
nos: 42297"
  },
  {
    "caption": "(A) Total cellular ATP levels were measured in l(2)mbn cells treated with control or Dcp-1 dsRNA. Data represent ± SEM of three independent experiments (n = 3). Statistical significance was determined using a two-tailed Students t test (*, P = 0.02).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(B) Total cellular ATP levels were measured in ovaries from fed or starved w1118 and Dcp-1Prev1 flies. Data represent ± SEM of five independent experiments (n = 5). Statistical significance was determined using a two-tailed Student's t test (**, P = 0.014; ***, P < 0.001).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(C) Fed or starved w1118 and Dcp-1Prev1 flies were treated with DMSO or 25 µg/ml oligomycin A, and Ref(2)P levels were assessed by immunoblot analysis. Actin served as a loading control. Densitometry was performed to quantitate protein levels relative to actin. Graph represents ± SD from three independent experiments (n = 3). Statistical significance was determined using a two-tailed Student's t test (*, P = 0.02).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(D and E) Control UASp-GFP-mCherry-DrAtg8a/+;nosGAL4/+ flies (D) and Dcp-1Prev1/Dcp-1Prev1;UASp-GFP-mCherry-DrAtg8a/nosGAL4 flies (E) were subjected to starvation conditions supplemented with DMSO or 25 µg/ml oligomycin A. Bars, 25 µm. Quantifications show percentage of autolysosomes (autolysosomes/total autophagic structures). At least eight egg chambers were manually quantitated per genotype per condition (n = 8). Statistical testing was determined using a two-tailed Student's t test. ***, P = 0.0002.",
    "ncbi_link": "Atg8a: 32001
Dcp-1: 37729
nos: 42297"
  },
  {
    "caption": "(A) A representative Western blot showing SesB and ATPsyn-α levels from fed or starved l(2)mbn cells treated with control or Dcp-1 RNAi. Actin served as a loading control. Densitometry was performed to quantitate protein levels relative to actin. Graphs represent ± SD from three independent experiments (n = 3). Statistical significance was determined using a two-tailed Student's t test (*, P < 0.05).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(B) A representative Western blot of ovaries from fed or starved w1118 or Dcp-1Prev1 flies. SesB and ATPsyn-α were detected by immunoblotting. Actin served as a loading control. Densitometry was performed to quantitate protein levels relative to actin. Graphs represent ± SD from three independent experiments (n = 3). Statistical significance was determined using a two-tailed Student's t test (*, P < 0.05).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(C) Purified catalytically active Dcp-1FL, but not catalytically inactive Dcp-1C<A, cleaved in vitro translated Drice. Cleavage of in vitro translated SesB was not detected.",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(D) V5-tagged Dcp-1C<A or V5 vector only control was expressed in l(2)mbn cells and subjected to nutrient-full or starvation conditions for 2 h. After IP with anti-V5 antibodies, lysates were separated by SDS-PAGE. Proteins were visualized with colloidal Coomassie stain.",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(E) FLAG-SesB or a vector only control was expressed in l(2)mbn cells and was immunoprecipitated with FLAG-agarose. Immunoblots show the interaction between FLAG-SesB and endogenous pro-Dcp-1. The asterisk represents a nonspecific band.",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(A) Ovaries from fed SesBOrg flies show reduced Ref(2)P staining in degenerating midstage egg chamber (arrow).",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(B) Ovaries from fed w1118 and SesBOrg were analyzed by Western blotting using Ref(2)P. Actin served as a loading control. Results are representative of three independent experiments (n = 3).",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(C) SesBOrg flies expressing GFP-mCherry-DrAtg8a in the germline showed increased autophagosomes and autolysosomes in nondegenerating (left) and degenerating (right) midstage egg chambers. Insets show autophagosomes and autolysosomes (left) and autolysosomes (right) in SesBOrg midstage egg chambers.",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(D) Quantitation of percentages of autolysosomes (autolysosomes/total autophagic structures) in nondegenerating ovaries from fed w1118 and SesBOrg flies. 10 egg chambers were manually examined per genotype. Error bars represent the means ± SD. Statistical significance was determined using a two-tailed Student's t test (***, P < 0.0001).",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(E) Degenerating midstage egg chambers (arrows) from fed SesBOrg flies are TUNEL positive.",
    "ncbi_link": "SesB: 32007"
  },
  {
    "caption": "(F) Degenerating midstage egg chambers from starved control SesBOrg/FM7a;Dcp-1Prev1/Dcp-1Prev1flies contained persisting nurse cellnuclei and increased Ref(2)P. n = 117 ovarioles examined. Box represents zoomed image. (G) Degenerating midstage egg chambers from fed SesBOrg;Dcp-1Prev1flies contained condensed and fragmented nurse cellnuclei and low levels of Ref(2)P. Box represents zoomed image. n = 156 ovarioles examined.",
    "ncbi_link": "Dcp-1: 37729
SesB: 32007"
  },
  {
    "caption": "(A) Co-immunoprecipitation (Co-IP) of Beclin1 with WT or mutant vBcl-2. 293T cells were transiently transfected with the indicated constructs, followed by immunoprecipitation of HA-tagged vBcl-2 and immunoblotting of V5-tagged Beclin1.",
    "ncbi_link": "Beclin1: 8678
Bcl-2: 1497180"
  },
  {
    "caption": "(B) Co-IP of WT or mutant vBcl-2 with endogenous Beclin1. 293T cells were transfected with the indicated vBcl-2 constructs, followed by immunoprecipitation of HA-tagged vBcl-2 and immunoblotting of endogenous Beclin1. 1% whole-cell lysates (WCLs) was used as the input.",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "(C) vBcl-2 interaction with Bak protein. 293T cells were transfected with WT and mutant forms of vBcl-2 as indicated. At 48 h posttransfection, WCLs were mixed either with GST-BakΔTM fusion protein (left panel) or with GST alone (right panel) for an in vitro GST pull-down (GST PD) assays. GST fusion proteins used for the pulldown assay are indicated (bottom panel). 1% WCL was used as the input. Data are representative of at least three experiments yielding similar results.",
    "ncbi_link": "Bak: 578
Bcl-2: 1497180"
  },
  {
    "caption": "(A) NIH3T3 cells stably expressing the WT and mutant forms of vBcl-2 were transfected with GFP-LC3. At 18 h posttransfection, cells were incubated under normal or starvation conditions for 4 h. Autophagy was quantified as mean±SEM of the combined results from three independent experiments. **, P<0.0001.",
    "ncbi_link": "Bcl-2: 1497180
LC3: 67443///66734"
  },
  {
    "caption": "(B) NIH3T3 cells expressing the WT or mutant forms of vBcl-2 as indicated were transfected with GFP-LC3 and treated with 2 µM rapamycin for 6 h. GFP-LC3 was detected using an inverted fluorescence microscope (top). Autophagy was quantified as mean±SEM of the combined results from three independent experiments. Scale bar, 5 µm; **, P<0.01.",
    "ncbi_link": "Bcl-2: 12043
LC3: 67443///66734"
  },
  {
    "caption": "(C) NIH3T3 cells stably expressing the WT or mutant forms of vBcl-2, as indicated, were treated with 2 µM rapamycin. LC3-I and LC3-II levels were then determined by immunoblotting with an antibody against LC3 (top). Densitometric quantification of the LC3-II/LC3-I ratios under normal and rapamycin treatment conditions is shown at the bottom. Similar results were obtained from three independent experiments.",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "(top) Representative confocal images of GFP-LC3 and HA-tagged vBcl-2 (WT and mutants) in NIH3T3 cells infected with the indicated viruses (MOI = 5). Nuclei were counterstained with 4′,6′-diamidino-2-phenylindole (DAPI). Scale bar, 5 µm. (bottom) Quantification of the percentage of virally infected cells with GFP-LC3 punctate staining. Results shown represent mean±SEM of combined results from three independent experiments (200 cells per experimental condition). *, P<0.01 versus HA-WT; **, P<0.001 versus HA-WT.",
    "ncbi_link": "LC3: 67443///66734
Bcl-2: P89884///1497180"
  },
  {
    "caption": "NIH3T3 cells stably expressing the WT or mutant forms of vBcl-2 were treated with TNFα and cycloheximide (CHX) for 12 h, then assayed for cell viability by trypan blue exclusion assay (A),",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "NIH3T3 cells stably expressing the WT or mutant forms of vBcl-2 were treated with TNFα and cycloheximide (CHX) for 12 h, then assayed for cell viability by trypan blue exclusion assay (A), or for apoptosis by TUNEL staining (B)",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "NIH3T3 cells stably expressing the WT or mutant forms of vBcl-2 were treated with TNFα and cycloheximide (CHX) for 12 h, then assayed for cell viability by trypan blue exclusion assay (A), or for apoptosis by TUNEL staining (B) or for the caspase 3 activation using flow cytometry (C). Apoptotic cells in (B) were counted under high power magnification (60×magnification). Mock, untreated condition. Data represents mean±SEM of combined results from three independent experiments. Scale bars, 100 µm (A), 5 µm (B). **, P<0.0001 versus vector cells.",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "(B) Acute replication of the WT and mutant vBcl-2 γHV68 viruses in the lungs of BALB/c mice at 5 dpi (up) and 7 dpi (down) after intranasal infection determined by viral titers in the lungs of the infected mice (left) or by real-time PCR of the viral genomic DNA (right). Mean±SEM of five mice per group/experiment. Data of 7 dpi is pooled from two separate experiments. The vBcl-2 Δα1 and ΔBH2 mutants did not yield significantly different results when compared to the WT in infectious virus titers [for Δα1, P = 0.82 (day 5); P = 0.08 (day 7); for ΔBH2, P = 0.49 (day 5); P = 0.54 (day 7); unpaired t-tests] and in viral genome loads in the lungs [for Δα1, P = 0.25 (day 5); P = 0.28 (day 7); for ΔBH2, P = 0.21 (day 5); P = 0.37 (day 7); unpaired t-tests]. n.s., not significant.",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "Splenic infectious centers measured at 12 dpi (A, left), 14 dpi (B, left), 21 dpi (C, left), 28 dpi (D, up), 35 dpi (E, up), or 42 dpi (F, up) and viral genome load measured by real-time PCR at 12 dpi (A, right), 14 dpi (B, right), 21 dpi (C, right), 28 dpi (D, down), 35 dpi (E, down), or 42 dpi (F, down), in the BALB/cmice intranasally infected with the WT or recombinant γHV68 mutants, as indicated (Mean±SEM of five mice per group/time point/experiment). Data of 14 dpi and 28 dpi is pooled from two and three separate experiments, respectively. Preformed infectious virus was negligible in all spleen samples. No significant difference was detected at 12 dpi (A), 14 dpi (B), and 21 dpi (C) with the Δα1 and ΔBH2 mutant viruses when compared to the WT in infectious center titers [for Δα1, P = 0.58 (day 12); P = 0.75 (day 14); P = 0.18 (day 21); for ΔBH2, P = 0.64 (day 12); P = 0.73 (day 14); P = 0.81 (day 21); unpaired t-tests] and in viral genome loads [for Δα1, P = 0.85 (day 12); P = 0.76 (day 14); P = 0.96 (day 21); for ΔBH2, P = 0.56 (day 12); P = 0.73 (day 14); P = 0.25 (day 21); unpaired t-tests]. At 28 dpi (D), 35 dpi (E), and 42 dpi (F), the decreased infectious center titers (top) of vBcl-2 mutant viruses, as compared to WT γHV68, were statistically significant [vBcl-2Δα1 versus vBcl-2AAA (42 dpi), P = 0.46; vBcl-2Δα1 versus WT γHV68 (42 dpi), P = 0.08; unpaired t-tests]. At 28 dpi (D), 35 dpi (E), and 42 dpi (F), the decreased viral DNA loads (bottom) of the vBcl-2Δα1, vBcl-2AAA, and vBcl-2 null mutants, as compared to WT γHV68 and the vBcl-2ΔBH2 mutant, were statistically significant as follows (unpaired t-tests): at day 28, vBcl-2Δα1 versus WT γHV68, P<0.01; vBcl-2AAA versus WT γHV68, P<0.01; vBcl-2-null versus WT γHV68, P<0.01; vBcl-2Δα1 versus vBcl-2ΔBH2, P<0.001; vBcl-2AAA versus vBcl-2ΔBH2, P<0.001; vBcl-2-null versus vBcl-2ΔBH2, P<0.001; at day 35, vBcl-2Δα1 versus WT γHV68, P<0.05; vBcl-2AAA versus WT γHV68, P<0.05; vBcl-2Δα1 versus vBcl-2ΔBH2, P<0.01; vBcl-2AAA versus vBcl-2ΔBH2, P<0.05; at day 42, vBcl-2Δα1 versus vBcl-2ΔBH2, P<0.001; vBcl-2AAA versus vBcl-2ΔBH2, P<0.001; vBcl-2ΔBH2 versus WT γHV68, P = 0.33. I.C., infectious center. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "ncbi_link": "Bcl-2: 1497180"
  },
  {
    "caption": "C-terminus motifs at parallel positions on E2F7 and E2F8 are essential for binding to cyclin F. The residues on each motif were mutated to alanines (R to A, I/L to A) with site-direct mutagenesis PCR. HEK293 cells were transfected with either EGFP-tagged empty vector (EGFP), wild-types E2F7/8 (WT) or alanine mutants. Nocodazole (50 ng/ml) was added 32 hours after transfection, and MG132 (1 μg/ml) was added 5 hours before harvesting at 48 hours post transfection. Cells were harvested and lysed for immunoprecipitation using anti-EGFP resin followed by immunoblotting with antibodies against cyclin F and EGFP.",
    "ncbi_link": "EGFP: 
E2F7: 144455"
  },
  {
    "caption": "Wild-type or mutant versions of EGFP-tagged E2F7/8 were co-transfected with either empty vector or Flag-tagged cyclin F in HEK293 cells. Nocodazole was added to cells 8h before harvest. 48 hours after transfection, cells were collected and lysed for immunoblotting.",
    "ncbi_link": "EGFP: 
Flag: 
cyclin F: 899
E2F7: 144455"
  },
  {
    "caption": "Knockdown of cyclin F stabilized E2F7 and E2F8. HeLa and RPE cells were transfected with either scramble siRNA or pool cyclin F siRNA. Cells were harvested at 48 hours post transfection. Protein levels of E2F7/8 were analyzed by immunoblotting. Asterisk indicates the specific band of E2F7 detection.",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Cyclin F targets atypical E2Fs during G2/M. HeLa cells were transfected with either scrambled siRNA (scr) or cyclin F siRNA (sicyclin F) for 24 hours. Then cells were synchronized by double thymidine block and released into fresh medium after the second block. Cells were harvested at the indicated timepoints after the release. Protein expression was measured by immunoblotting and cell cycle progression was determined by flow-cytometry (shown in Fig EV 1A). Asterisk indicates the specific detection of endogenous E2F7.",
    "ncbi_link": "Cyclin F: 899
cyclin F: 899"
  },
  {
    "caption": "Cyclin F contributes to the ubiquitylation of E2F7 and E2F8 in vivo. HEK293 cells were transfected with HA-E2F7/8, with or without Flag-cyclin F, and with HA-tagged ubiquitin. 5 hours before harvest, cells were treated with MG132. 48 hours after transfection, HEK cells were harvested and lysed for immunoprecipitation pull-down assay with anti-HA resin followed by immunoblotting.",
    "ncbi_link": "Flag: 
HA: 
cyclin F: 899
E2F7: 144455
ubiquitin: 7314"
  },
  {
    "caption": "Schematic view of the experimental setting for the HU-synchronized live cell imaging. 48 hours before imaging, RPE-FUCCI cells were transfected with siRNA against scramble or cyclin F. 16 hours before imaging, cells were synchronized at the G1/S border by HU (2 mM) treatment. Representative images from different channels are shown, and white arrows in Differential Interference Contrast DIC channel indicate the traced cell. Scale bar: 10µm.",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Quantification of the number of Ctrl (left panel) and 7/8KO (right panel) RPE-FUCCI cells with scr or sicyclin F that completed mitosis after HU release. For each condition, 100 cells were monitored by live cell imaging. Each cell was followed until it successfully finished mitosis and divided into two daughter cells for a maximum of 24 hours. Log-rank tests were performed to analyze the statistical significance.",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Schematic view of the experimental setting for live imaging of asynchronous cells. 48 hours before imaging, RPE-FUCCI cells were transfected with siRNA against scramble or cyclin F. At the start of the imaging, G1 cells (red: mKO2-Cdt1 > mAG1-Geminin, 50 cells per condition) were enrolled and subsequently monitored though their entire cell cycle until mitosis. The black dot represents mitosis.",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Knockdown of cyclin F causes a delay in mitotic entry that is dependent on E2F7 and E2F8. Number of Ctrl (left panel) or 7/8KO (right panel) RPE-FUCCI cells with scr or cyclin F RNAi that finished mitosis during live cell imaging is shown. For each condition, 50 cells at G1 were monitored by live cell imaging. Each cell was followed until it successfully progressed through S and G2 phase, finished mitosis and divided into two daughter cells, for a maximum of 24 hours. Log-rank tests were performed to analyze the statistical significance.",
    "ncbi_link": "cyclin F: 899
E2F7: 144455
E2F8: 79733"
  },
  {
    "caption": "Loss of cyclin F delays the progression from G1/S transition to mitosis. Histogram shows the time from G1/S (mAG1-Geminin intensity increases to higher than 10% of the maximum value in three consecutive imaging frames) to completed mitosis. Only cells that finished mitosis were enrolled in this quantification. Student t-test was used to test the statistical significance, asterisks indicates the P value <0.01. Bar and error bars represent mean ± SEM.",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Depletion of cyclin F stalls the cell cycle at late S/G2. After 24 hours of live cell imaging, the cell cycle progression from panel E was quantified. Histogram shows the percentage of cells at each stage (at 24h) over the whole population (50 cells per condition).",
    "ncbi_link": "cyclin F: 899"
  },
  {
    "caption": "Disruption of cyclin F binding site increased stability of E2F7. E2F7WT and E2F7R894A constructs were integrated in to HeLa/TO system. Cells were arrested with HU for 16 hours before releasing into doxycycline containing medium, and cells were collected every 3 hours for immunoblotting.",
    "ncbi_link": "E2F7: 144455"
  },
  {
    "caption": "qPCR showing that mRNA level of E2F7WT and E2F7R894A were at comparable levels. Bar and error bars represent mean ± SEM.",
    "ncbi_link": "E2F7: 144455"
  },
  {
    "caption": "Over-expression of E2F7R894A delays cell cycle progression through G2-M phase. HeLa/TO cells expressing either wild-type or mutant version of E2F7 were arrested with 16h of HU, and then cells were released into fresh medium with or without doxycycline. Live cell imaging was performed to trace the G2-M progression of HeLa/TO cells.",
    "ncbi_link": "E2F7: 144455"
  },
  {
    "caption": "Heatmap showing differentially expressed genes after cyclin F knockdown, and rescued by additional E2F7/8 depletion. Highlighted genes are all involved in DNA repair. Cells were arrested with nocodazole for 16 hours prior to harvesting to minimize bias from potential differences in cell cycle progression between the different conditions.",
    "ncbi_link": "cyclin F: 899
E2F7: 144455"
  },
  {
    "caption": "Loss of cyclin F induced E2F7/8-dependent Homologous Recombination deficiency. HeLa cells that were stably transformed with pDR-GFP were transfected with siRNA as indicated.48h after the initial transfection, cells were harvested for Flow-cytometry. GFP positive cells were gated (Fig EV5A). Relative HR efficiency were adjusted to the scramble siRNA condition. Data represent averages ± SEM (n=3); **P<0.01 (Student's t-test). n.s.: not significant.",
    "ncbi_link": "GFP: 
pDR: 
cyclin F: 899
E2F7: 144455"
  },
  {
    "caption": "Loss of cyclin F induced E2F7/8-dependent γ-H2AX accumulation. HeLa cells were transfected with indicated siRNA for 24 hours, and then treated with nocodazole for 16 hours before fixation for immunofluorescence staining of γ-H2AX. DAPI was used to stain the cell nucleus. Relative intensity of γ-H2AX was quantified by Image J software, and 150 cells were quantified for each condition. Red bars represent averages; **P<0.01 (Student's t-test). n.s.: not significant. Scale bar 20 μm.",
    "ncbi_link": "cyclin F: 899
E2F7: 144455"
  },
  {
    "caption": "Loss of cyclin F increased DNA damage recovery time before cell division. RPE cells integrated with the 53BP1 construct were transfected with indicated siRNA for 24 hours, and then treated with HU for 16 hours. At the beginning of the imaging, only the single cells with at least one 53BP1 foci were traced, till the time frame that no 53BP1 foci was observed. The mitotic progression of the cells was defined as the duration from damage recovery to cell division. Histogram shows the damage recovery time (green) and the mitotic progression (black) of 50 cells for each condition. Chi-square analysis was performed to test the statistical significance (P<0.01).",
    "ncbi_link": "cyclin F: 899
53BP1: 7158"
  },
  {
    "caption": "Knockdown of cyclin F caused a delay in DNA lesion recovery that is dependent on E2F7/8. The cumulative curves represent the add-up number of cells that overcome the DNA damage lesions, for a time frame of 24 hours. For each condition, 50 cells were quantified. Log-rank tests were performed to analyze the statistical significance.",
    "ncbi_link": "cyclin F: 899
E2F7: 144455"
  },
  {
    "caption": "Fluorescence was observed in the transformed N. benthamiana leaf epidermal cells, which results from complementation of the N-terminal part of the YFP fused with ATG8a (ATG8a-N-YFP) by the C-terminal part of the YFP fused with NBR1 (NBR1-C-YFP). No fluorescence was observed when ATG8a-N-YFP was coexpressed with unfused C-YFP or with mNBR1-C-YFP or when unfused N-YFP was coexpressed with NBR1-C-YFP. YFP epifluorescence images, bright-field images and overlay images of the same cells are shown.",
    "ncbi_link": "ATG8a: 
NBR1: "
  },
  {
    "caption": "(A) Four-weeks old transgenic wild-type Col-0 (WT) and atg7-2 mutant plants expressing GFP-ATG8a were treated with (45°C) or without (22°C) heat shock for 3 h and then placed at room temperature for 0.5 h. The leaves were visualized by fluorescence confocal microscopy of GFP signal. (B) Numbers of punctate GFP-ATG8a spots representing autophagosomes per 10,000 µm2 section. Means and SE were calculated from three experiments. According to Duncan's multiple range test (P = 0.05), means do not differ significantly if they are indicated with the same letter. Bar = 20 µm.",
    "ncbi_link": "atg7-2: 834630"
  },
  {
    "caption": "(Top panel) Four-weeks old transgenic wild-type Col-0 (WT), atg7-2 and nbr1-1 mutant plants expressing GFP-NBR1 were treated with (45°C) or without (22°C) heat shock for 3 h and then placed at room temperature for 0.5 h. The leaves were visualized by fluorescence confocal microscopy of GFP signal. (Bottom panel) Numbers of punctate GFP-NBR1 spots per 10,000 µm2 section. Means and SE were calculated from three experiments. According to Duncan's multiple range test (P = 0.05), means do not differ significantly if they are indicated with the same letter. Bar = 20 µm.",
    "ncbi_link": "atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(A) Five weeks-old Arabidopsis Col-0 wild type (WT), atg5, atg7 and nbr1 mutant plants were placed in 22°C and 45°C growth for 10 hours and then moved to room temperature for 3-day recovery or (B) sprayed with 20 µM methyl viologen (MV) and kept under light for two days before the picture of representative plants was taken. The experiments were repeated three times with similar results.",
    "ncbi_link": "atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(B) Fv/Fm images. (C) Average values for the Fv/Fm images. Five weeks-old Arabidopsis Col-0 wild type (WT), atg5, atg7 and nbr1 mutant plants were placed in 22°C and 45°C growth chambers. Fully expanded leaves were sampled after 10 hours in the indicated temperatures and immediately measured for electrolyte leakage and Fv/Fm. Error bars in (A) and (C) indicate SE (n = 5). According to Duncan's multiple range test (P = 0.05), means of EL or Fv/Fm do not differ significantly if they are indicated with the same letter. The experiments were repeated twice with similar results.",
    "ncbi_link": "atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(A) Five weeks-old Arabidopsis Col-0 wild type (WT), atg5, atg7 and nbr1 mutant plants were placed into a growth chamber with approximately 50% humidity. The photograph of representative plants was taken 10 days after withholding watering. The experiment was repeated twice with similar results.",
    "ncbi_link": "atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(B) Seven days-old seedlings Col-0 WT, atg5, atg7 and nbr1 grown on solid MS medium were transferred to the same medium (control) or the same medium containing 0.16 M NaCl and photographed 5 days later. The survived seedlings were scored 5 days after the transfer and the average values and SE were calculated from three experiments. According to Duncan's multiple range test (P = 0.05), means do not differ significantly if they are indicated with the same letter.",
    "ncbi_link": "atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(A) Eight weeks old wild type (WT), atg5, atg7 and nbr1 plants grown under normal growth conditions in a growth chamber. (B) Four weeks old WT, atg5, atg7 and nbr1 plants after being kept in the dark for 6 days. (C) Percentage of plants that survived the various lengths in dark as determined by resumption of growth. Each point represents the average of 10 plants. The experiments were repeated twice with similar results.",
    "ncbi_link": "atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(A) Responses of Col-0 wild type (WT), atg5, atg7 and nbr1 plants to Botrytis. Wild-type and mutant plants were inoculated by spraying with spore suspension at a density of 2.5×105 spores ml−1, and kept at high humidity. Pictures of representative plants were taken at 4 and 5 days post inoculation (dpi). (B) Quantitative real-time PCR analysis of the B. cinerea ActA (BcActA) transcript levels in infected Arabidopsis plants at 5 dpi. The experiments were repeated twice with similar results.",
    "ncbi_link": "ActA: 
atg5: 831594
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(A) Diagrams of wild-type and mutant NBR1 proteins. The conserved W and I residues in the LIR motif between the two UBA domains were changed to A residues in the NBR1W661A/I664A (mNBR1) mutant protein. (B) Five weeks-old Arabidopsis Col-0 wild type (WT), nbr1 and transgenic nbr1 plants expressing the wild-type NBR1 (lines 3 and 6; see Figure S2) or the NBR1W661A/I664A (mNBR1) (lines 2 and 6; see Figure S2) mutant gene were placed in a 45°C growth chambers for 10 hours and then moved to room temperature for 3-day recovery before the picture as taken. The experiment was repeated three times with similar results.",
    "ncbi_link": "nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "Leaf tissues from wild type (WT) and atg7 expressing NBR1-TAP were collected at indicated hours (h) under 45°C and prepared for soluble and insoluble proteins as described in Materials and Methods. Proteins from the first supernatants (S) and last pellets (P) were subjected to SDS-PAGES and probed with a peroxidase-conjugated anti-peroxidase antibody for detection of NBR1-TAP. Protein samples prepared from non-transgenic Col-0 wild-type plants were included as controls.",
    "ncbi_link": "atg7: 834630"
  },
  {
    "caption": "(A) Accumulation of insoluble proteins. Leaf tissues from wild-type (WT), atg7 and nbr1 mutants collected at indicated hours (h) under 45°C for preparation of total, soluble and insoluble proteins as described in Materials and Methods. Total proteins in the starting homogenates and insoluble proteins in the last pellets were determined the percentages of insoluble proteins to total proteins were calculated. (B) Profiles of soluble and insoluble proteins. Proteins from the first supernatants (S) and last pellets (P) were subjected to SDS-PAGES and stained with Coomassie brilliant blue. Major proteins accumulated in the pellets from heat-stressed atg7 mutant plants were indicated by arrows.",
    "ncbi_link": "atg7: 
atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "Leaf tissues from wild type (WT), atg7 and nbr1 mutants were collected at indicated hours (h) under 45°C and prepared for soluble and insoluble proteins as described in Materials and Methods. Proteins from the first supernatants (S) and last pellets (P) were subjected to SDS-PAGES and probed with anti-ubiquitin monoclonal antibody. The experiment was repeated three times with similar results.",
    "ncbi_link": "atg7: 834630
nbr1: 828571"
  },
  {
    "caption": "(E&F)  Gli1-tdTomato+ cells expanded primarily in the outer medullary region. In contrast, COUP-TFII+ cells are distributed both in cortex and medulla. A subset of COUP-TFII+ cells (green) overlap with genetically labeled Gli1+ pericyte/perivascular  cells (red) in  UUO injury model (n=3 animals per group). CTL:  contralateral kidney. Quantification by confocal micrographs in 200x hpf.",
    "ncbi_link": "Gli1: 14632"
  },
  {
    "caption": "(D) COUP-TFII+ cells decrease significantly in the UUO kidney in TAM-treated homozygous (F/F;Cre/+) mice (KO group, n=6) compared to wild-type littermates (WT group, n=4). Expression of αSMA (red) and collagen1 (yellow) are also markedly reduced. Masson Trichrome staining  shows less kidney fibrosis in KO compared to WT group. Quantification by confocal micrographs in 200x hpf. **p<0.01 by unpaired t test, mean ± SD.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "(D) COUP-TFII-OE cells, in the absence of TGFβ1 stimulation, displayed an elongated fibroblast shape with increased αSMA expression, similar to WT cells treated with TGFβ1. Quantification by confocal micrographs in 400x hpf, *p<0.05, **p<0.01, ***p<0.001 by one-way ANOVA, mean ± SD.",
    "ncbi_link": "COUP-TFII: 11819"
  },
  {
    "caption": "(E) Overexpression of COUP-TFII alone without TGFβ1 induces collagen1 production (n=3). *p<0.05, **p<0.01, ***p<0.001 by one-way ANOVA, mean ± SD.",
    "ncbi_link": "COUP-TFII: 11819"
  },
  {
    "caption": "(D) WT, COUP-TFII overexpression (OE) and COUP-TFII knockout (KO) cells were seeded in Seahorse XF-24 cell culture microplates. The cells were rendered quiescent in 0.5% FBS DMEM overnight and then treated with or without 10 ng/ml TGFβ1 for 24 hours. All the cells were incubated in the glycolysis stress test medium without glucose and pyruvate, followed by sequential treatments with glucose (10mM), oligomycin (5μg/ml) and 2-DG (50mM). Real-time extracellular acidification rate (ECAR) was recorded as the baseline (before  glucose), the rate of glycolysis (after glucose), glycolytic capacity (after oligomycin), and glycolytic reserve (after 2-DG) (n = 10).",
    "ncbi_link": "COUP-TFII: 11819"
  },
  {
    "caption": "(E) COUP-TFII OE significantly increased, while COUP-TFII KO decreased, in the baseline, rate of glycolysis, glycolytic capacity, and glycolytic reserve when compared to WT cells under  TGFβ1 stimulation. Without TGFβ1 treatment, there is no difference on the baseline and glycolysis among WT, OE, and KO cells. COUP-TFII  KO significantly decreased glycolytic capacity and reserve compared to WT, even without TGFβ1 stimulation (n=10), *p<0.05; **p<0.01; ****p<0.0001 by one-way ANOVA, mean ± SD.",
    "ncbi_link": "COUP-TFII: 11819"
  },
  {
    "caption": "(A) Volcano plot of all detected proteins from  proteomics of TGFβ-treated naïve (WT) and COUP-TFII overexpressing (COUP-TFII-OE) cells. PDK4 expression is significantly decreased in OE cells (n=2).",
    "ncbi_link": "COUP-TFII: 11819"
  },
  {
    "caption": "(E) PGC1α OE significantly increased expression of Cpt1 and  PDK4, both are involved in key steps of FAO. However, overexpression of PGC1α did not abrogate the TGFβ1 up-regulated genes in glycolysis and αSMA (n=6). *p<0.05; **p<0.01; ****p<0.0001 by one-way ANOVA, mean ± SD.",
    "ncbi_link": "SMA: 59
Cpt1: 12894
PDK4: 27273
PGC1α: 19017"
  },
  {
    "caption": "Determination of maximum growth rate (Vmax) using a label-free cell count-based proliferation assay. Representative growth curves of WT and NUP58 mutant clone F are plotted using a semi-log scale displaying total numbers of cells over time. Growth rates were calculated across the entire duration of the experiment using a sliding window of three timepoints.",
    "ncbi_link": "NUP58: 9818"
  },
  {
    "caption": "Western blot for NUP58 protein expression in mutant clones and control cells. Whole-cell lysate hybridized with customized antibody 1 (Ab1, top panel) and antibody 2 (Ab2, bottom panel). Blots were loaded with wild-type HAP1 cell line (WT), empty vector (EV), non-targeting siRNA (siNT) and NUP58 targeting siRNA (siNUP58), followed by NUP58 mutant clones (C1 / C2 / C3 / C4 in left panels, C5 / C6 in right panels). Actin was used as loading control. Asterisks indicate possible NUP58 alternative isoforms.",
    "ncbi_link": "NUP58: 9818"
  },
  {
    "caption": "Cellular viability expressed as number of viable colonies following Cas9-induced gene editing of NUP58 in WT cell line and in a cell line stably overexpressing KPNB1-KPNA4-eGFP (KAPs).",
    "ncbi_link": "eGFP: 
KPNA4: 3840
KPNB1: 3837
NUP58: 9818"
  },
  {
    "caption": "Cellular viability following Cas9-induced gene editing of native NUP58 (left) or NUP85 (right) in WT cell line (black circles) and in a cell line overexpressing NUP58 mutant isoform (grey circles).",
    "ncbi_link": "NUP58: 9818
NUP85: 79902"
  },
  {
    "caption": "Diagram at the top represents G-banding pattern of chromosome 13 and highlights chromosome locations of tested genes (NUP58, GRK1, ADPRHL1). Graph at the bottom reports qPCR results for indicated genes preformed on the gDNA of indicated samples at the indicated passage number.",
    "ncbi_link": "ADPRHL1: 113622
GRK1: 6011
NUP58: 9818"
  },
  {
    "caption": "Representative images of NUP58 gene-specific FISH hybridization for control HAP1 cell lines (WT P3-WT P19) and mutant C5 at P19. Each dot represents a NUP58 locus of cluster thereof. Scale bar, 31.3 μm",
    "ncbi_link": "NUP58: 9818"
  },
  {
    "caption": "Quantitative RT-qPCR analysis of relative expression of Cd9 normalized to Gapdh in HUVEC after stimulation with either control (blue diamond, n = 9) or PBMC TDB-conditioned supernatant (lilac square, n = 3) for 6 h and 24 h.",
    "ncbi_link": "Cd9: 928
Gapdh: 2597"
  },
  {
    "caption": "Quantification of T cell adhesion to a monolayer of HUVECs transfected with either negative control siRNA (black) or CD9-specifc siRNA (green) under shear stress-like conditions (100 rpm) treated with the indicated conditions. All done in biological duplicates with four technical replicates per biological replicate. Representative data of one experiment shown. FOV: field of view.",
    "ncbi_link": "CD9: 928"
  },
  {
    "caption": "(A) The indicated yeast strains (wild type, pex19Δ, pex3Δ, msp1Δ, pex19Δmsp1Δ, and pex3Δmsp1Δ) expressing RFP-SKL (peroxisomal marker) and mitochondria-targeted green fluorescent protein (mGFP) were grown to mid-log phase and imaged by fluorescence microscopy. Representative images are shown, scale bar, 2 μm. DIC, differential interference contrast. Enhanced: the red signal intensity was set to 'best-fit' in ZENPro microscopy software analysis.",
    "ncbi_link": "msp1: 852915
pex19: 851494
pex3: 851929"
  },
  {
    "caption": "(B) Volcano plot showing the most enriched/decreased proteins in the mitochondrial proteome of pex19Δ versus pex19Δmsp1Δ strains as detected by quantitative mass spectrometry (n=7, biological replicates; n=2, technical replicates). Effect sizes were calculated for Cohen's d A protein's relevance was determined using a p-value threshold of < 0.05 with an absolute effect size threshold of 1 or greater (large effect). Gray dots represent all measured proteins and red dots highlight peroxisomal-associated proteins.",
    "ncbi_link": "msp1: 852915
pex19: 851494"
  },
  {
    "caption": "(F) Total yeast cell lysate, post mitochondrial supernatant, and HistodenzTM-purified mitochondria from the indicated strain (wild type, msp1Δ, pex19Δ, pex19Δmsp1Δ, pex3Δ, and pex3Δmsp1Δ) expressing Pex13-V5 (under its endogenous promotor) were separated by SDS-PAGE and immunoblotted for Pex13 (α-V5), cytochrome c (α-cyt c), and HSP70 (α-hsp70). (G) Total yeast cell lysate, post mitochondrial supernatant, and HistodenzTM-purified mitochondria from the indicated strain (wild type, msp1Δ, pex19Δ, pex19Δmsp1Δ, pex3Δ, and pex3Δmsp1Δ) expressing Pex11-V5 (under its endogenous promotor) were separated by SDS-PAGE and immunoblotted for Pex11 (α-V5) and porin (α-porin), cytochrome c (α-cyt c), and HSP70 (α-hsp70). ",
    "ncbi_link": "msp1: 852915
pex19: 851494
pex3: 851929"
  },
  {
    "caption": "(A) Volcano plot (log10) of the most enriched/decreased proteins in the mitochondrial proteome of pex3Δ versus pex3Δmsp1Δ strains as detected by quantitative mass spectrometry (n=3, biological replicates, n=1, technical replicate). 2010). Effect sizes were calculated for Cohen's d A protein's relevance to the model was determined using a p-value threshold of < 0.05 with an absolute effect size threshold of 1 or greater (large effect). Gray dots represent all measured proteins. Red dots highlight peroxisomal-associated proteins.",
    "ncbi_link": "msp1: 852915
pex3: 851929"
  },
  {
    "caption": "(C) Mitochondria from the indicated yeast strains (wild type, pex19Δ, pex19Δmsp1Δ), expressing Pex13-V5 (under its endogenous promotor) were either left untreated (lane 1,2,3) or exposed to Na2CO3 and separated into the membrane pellet (4,5,6) or supernatant fraction (7,8,9). After separation by SDS-PAGE the fractions were immunoblotted for Pex13-V5 (α-V5) and porin (α-porin).",
    "ncbi_link": "msp1: 852915
pex19: 851494"
  },
  {
    "caption": "(B) Digitonin-solubilized (1 or 4 g/g digitonin/protein ratio, as indicated) mitochondrial membranes from the indicated yeast strains (wild type, pex19Δ, pex19Δmsp1Δ) expressing Pex13-V5 (under its endogenous promotor) were separated by BN-PAGE with a 3-18% gradient and stained with Coomassie brilliant blue. BHM, bovine heart mitochondria; V2, complex V-dimer; SL,supercomplex III2IV2; Ss, supercomplex III2IV1; V1, complex V-monomer.",
    "ncbi_link": "msp1: 852915
pex19: 851494"
  },
  {
    "caption": "(F) Mitochondria from the indicated yeast strains (pex19Δ, pex19Δmsp1Δ, and pex13Δmsp1Δpex19Δ) expressing Pex22-V5 (under its endogenous promotor) (HistodenzTM-purified) were separated by SDS-PAGE and immunoblotted for Pex22-V5 (α-Pex22-V5) and porin (α-porin). (G) Mitochondria from the indicated yeast strains (pex19Δ, pex19Δmsp1Δ, and pex13Δmsp1Δpex19Δ ) expressing Pot1-V5 (under its endogenous promotor) were separated by SDS-PAGE and immunoblotted for Pot1-V5 (α-Pot1-V5) and porin (α-porin). (H) Mitochondria from the indicated yeast strains (pex19Δ, pex19Δmsp1 Δ, and pex13Δmsp1Δpex19Δ) expressing Mdh3-V5 (under its endogenous promotor) (HistodenzTM-purified) were separated by SDS-PAGE and immunoblotted for Mdh3-V5 (α-Mdh3-V5) and porin (α-porin).",
    "ncbi_link": "msp1: 852915
pex13: 850888
pex19: 851494"
  },
  {
    "caption": "(I) Mitochondria from the indicated yeast strains (pex19Δ, pex19Δmsp1Δ, and pex13Δmsp1Δpex19Δ) expressing Pot1-V5 (under its endogenous promotor) were either left untreated (nt) (lane 1,4,7) or were treated with proteinase K in high fidelity buffer (PK-HF) (cutting control, lane 2,5,8) or low fidelity buffer (PK-LF) (protease protection assay, lane 3,6,9) and separated by SDS-PAGE and immunoblotted for Mia40 (intermembrane space) (α-Mia40), Pot1-V5 (α-V5), porin (outer membrane) (α-porin) and Tom22 (outer membrane but partially proteinase exposed) (α-Tom22).",
    "ncbi_link": "msp1: 852915
pex13: 850888
pex19: 851494"
  },
  {
    "caption": "(A) Fluorescence microscopy of human fibroblast cell lines derived from ZSD patients-cWT, cWT+ATAD1, PEX3-/-, and PEX3-/-+ATAD1-expressing PEX13-GFP and stained with Mitotracker Deep Red FM. Representative images are shown, scale bar, 10 μm.",
    "ncbi_link": "ATAD1: 84896
PEX3: 8504"
  },
  {
    "caption": "(B) Electron microscopy of human fibroblast cell lines cWT, cWT+ATAD1, PEX3-/-, and PEX3-/-+ATAD1. Representative images are shown, scale bar 500 nm.",
    "ncbi_link": "ATAD1: 84896
PEX3: 8504"
  },
  {
    "caption": "(A) Bioenergetic profile of human fibroblast cell lines. OCR (pmol/min/norm.unit) for cWT, cWT+ATAD1, PEX3-/-, PEX3-/-+ATAD1, cWT-ATAD1-/-, and PEX3-/- atad1-/- cells plotted against time (XF96e Extracellular Flux Analyzer, Mito-Stress-Test). 1 μM Oligomycin A, 0.15 μM FCCP, and 1 μM rotenone + 1 μM antimycin A (final concentrations) were sequentially delivered to the XF96e assay medium through injection ports in the sensor cartridge. The graph is the compilation of two independent assays, error bars show mean +/- s.d. (n=4, biological replicates).",
    "ncbi_link": "ATAD1: 84896
atad1: 84896
PEX3: 8504"
  },
  {
    "caption": "(E) Scatter plot representation of cardiolipin lipidomics. The average (n = 4, biological replicates) normalized peak intensity of each of the 11 detected cardiolipin species, log10 pareto-scaled is visualized. The horizontal lines represent the mean peak intesity of all 11 caridolipin species in each cell line. ­­(F) Scatter plot representation of a subpopulation of the phosphoethanolamine (PE) lipidomics. The average (n = 4, biological replicates) normalized peak intensity of each of the 20 phosphoethanolamine (PE) species (decreased in PEX3-/-), log10 pareto-scaled, is visualized. The horizontal lines represent the mean peak intesity of all 20 PE species in each cell line. (G) Scatter plot representation of ether-phospholipid lipidomics. The average (n = 4, biological replicates) normalized peak intensity of each of the 21 detected ether-phospholipid (plasmalogen) species, log10 pareto-scaled, is visualized. The horizontal lines represent the mean peak intesity of all 21 plasmalogen species in each cell line.",
    "ncbi_link": "PEX3: 8504"
  },
  {
    "caption": "E, Time lapse video-microscopy snapshot on HeLa cells transfected with NAF-1-mRFP (red) and treated with fluoMito-C (green). The distance/intensity fluorescence quantification graph illustrates the codistribution of fluoMito-C and NAF-1-mRFP.",
    "ncbi_link": "mRFP: 
NAF-1: "
  },
  {
    "caption": "A, Western blot analysis of MitoNEET expression in HeLa cells transfected with CISD1 siRNA; Bar Chart (right panel) shows replicates quantification of MitoNEET expression. Errors bars show the standard deviation (SD) of 3 independent experiments.",
    "ncbi_link": "CISD1: 55847"
  },
  {
    "caption": "B, Western blot analysis of NAF-1 expression in HeLa cells transfected with CISD2 siRNA; graph (right panel) shows the replicates quantification of NAF-1 expression. Errors bars show the standard deviation (SD) of 3 independent experiments.",
    "ncbi_link": "CISD2: 493856"
  },
  {
    "caption": "D, HeLa cells transfected with siRNA to reduce expression of MitoNEET (CISD1), NAF-1 (CISD2) or MiNT (CISD3) and immunostained with anti TOM20 antibody. Arrowheads indicate fragmented mitochondria.",
    "ncbi_link": "CISD1: 55847
MitoNEET: 55847
CISD2: 493856
NAF-1: 493856
CISD3: 284106
MiNT: 284106"
  },
  {
    "caption": "E, Quantification of mitochondria morphology (based on TOM20 immunostaining as shown in D) from HeLa cells transfected with siRNA targeting mitoNEET (siCISD1), NAF1 (siCISD2) or MiNT (siCISD3). Quantification is expressed as ratio of tubular and fragmented mitochondria. Errors bars show the standard error of the mean (SEM). (n =125-130 cells).",
    "ncbi_link": "CISD1: 55847
CISD2: 493856
mitoNEET: 493856
NAF1: 493856
CISD3: 284106
MiNT: 284106"
  },
  {
    "caption": "G, Western blot analysis of NAF-1 expression in cells stably transfected with control shRNA, shRNA targeting reduction of NAF-1 protein expression (shCISD2), or shRNA targeting reduction of NAF-1 protein expression complemented with plasmid derived expression of NAF-1 (shCISD2+CISD2); western blot quantification of NAF-1 is shown on the accompanying bar chart. Errors bars show the standard deviation (SD) of 3 independent experiments.",
    "ncbi_link": "CISD2: 493856"
  },
  {
    "caption": "E, HeLa cells were transfected with DRP1K38A mutant and mCherry and treated or not, with Mito-C (T for transfected, NT for not transfected). F, Quantification of the mitochondrial phenotypes observed in E. Errors bars show the standard error of the mean (SEM). (30-35 images each with an average of 15-20 cells from triplicate independent experiments were analyzed). G",
    "ncbi_link": "DRP1: 10059"
  },
  {
    "caption": "Schematic of a line‐scan FRAP experiment. Fluorescence intensities are measured along a line of a non‐bleached nucleus (Ctrl nucleus) and a bleached nucleus (FRAP nucleus) in Swi6‐EGFP clr4∆ cells. Red box: bleached region. Right: raw data example.",
    "ncbi_link": "clr4: 2540825"
  },
  {
    "caption": "Average relative intensities of a line‐scan FRAP experiment on Swi6‐EGFP in heterochromatin (blue line), euchromatin (green line), and clr4∆ (red line). The curves have a gliding average of 40.",
    "ncbi_link": "clr4: 2540825"
  },
  {
    "caption": "A, BAverage relative intensities over time and corresponding fluorescence t 1/2 values of heterochromatic Swi6 obtained from FRAP experiments performed with cells expressing NLS‐Swi6‐EGFP (blue) or NLS‐Swi6‐KR25A‐EGFP (red).",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "C, DAverage relative intensities over time and corresponding fluorescence t 1/2 values of heterochromatic Swi6 obtained from FRAP experiments performed with wild‐type (brown) or cid14∆ (dark green) cells expressing Swi6‐EGFP.",
    "ncbi_link": "cid14: 3361384"
  },
  {
    "caption": "E, FAverage relative intensities over time and corresponding fluorescence t 1/2 values of heterochromatic Swi6 obtained from FRAP experiments performed with wild‐type cells expressing heterochromatic NLS‐Swi6‐EGFP (blue) or NLS‐Swi6 KR25A‐EGFP (red), or cid14∆ cells expressing NLS‐Swi6‐EGFP (green) or NLS‐Swi6‐KR25A‐EGFP (yellow).Data information: In (B), (D) and (F), the box bounds the interquartile range (IQR) divided by the median, and whiskers extend to a maximum of 1.5 × IQR beyond the box.",
    "ncbi_link": "cid14: 3361384
Swi6: 2541633"
  },
  {
    "caption": "Fluorescence t 1/2 values of centromeric or telomeric Swi6 obtained from FRAP experiments performed with cells expressing NLS‐Swi6‐EGFP.",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "Fluorescence t 1/2 values of centromeric or telomeric Swi6 obtained from FRAP experiments performed with cells expressing the RNA‐binding mutant NLS‐Swi6‐KR25A‐EGFP.Fluorescence t 1/2 values of centromeric or telomeric Swi6 obtained from FRAP experiments performed with cells expressing Swi6‐EGFP.",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "Fluorescence t 1/2 values of centromeric Swi6 obtained from FRAP experiments performed after release of cells expressing NLS‐Swi6‐EGFP (black dots) or the RNA‐binding mutant NLS‐Swi6‐KR25A‐EGFP (red dots) from G1/S cell cycle arrest. Each dot represents one FRAP experiment at the respective time after release from cell cycle arrest. Swi6 is dispersed in M phase due to H3S10 phosphorylation, and M phase was therefore not included in the FRAP analysis.",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "Fluorescence t 1/2 values obtained from FRAP experiments performed on centromeric Swi6 of cells expressing NLS‐Swi6‐EGFP and NLS‐Swi6‐KR25A‐EGFP that reside in the G2 of the cell cycle.",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "Fluorescence t 1/2 values of centromeric or telomeric Swi6 obtained from FRAP experiments performed with cells expressing the RNA‐binding mutant NLS‐Swi6‐KR25A‐EGFP.",
    "ncbi_link": "Swi6: 2541633"
  },
  {
    "caption": "H3K9me2 ChIP‐seq enrichment profiles for swi6+ and swi6∆ cells on centromere 1. Centromeric repeat elements (dg/dh) are indicated. Inverted repeats (IRC1) constitute heterochromatin boundaries in wild‐type cells (Cam et al, 2005). The y‐axes represent log2 ChIP‐seq enrichments in 200‐bp genomically tiled windows calculated over clr4Δ cells. Two independent biological replicates for each genotype were performed (replicates 1 and 2). Positions of genomic elements on the plus and minus strands are indicated. Blue, protein‐coding genes; white, repeats; green, long terminal repeat (LTR).",
    "ncbi_link": "clr4: 2540825
swi6: 2541633"
  },
  {
    "caption": "H3K9me2 ChIP‐seq enrichment profiles for swi6+ and swi6∆ cells on the telomere of the right arm of chromosome 1. Two independent biological replicates for each genotype were performed (replicates 1 and 2).",
    "ncbi_link": "swi6: 2541633"
  },
  {
    "caption": "Differential expression of transcripts coming from centromere 1 assessed by tiling microarray gene expression analysis. Expression data for swi6+ and swi6∆ cells were taken from a previous publication (Woolcock et al, 2012).",
    "ncbi_link": "swi6: 2541633"
  },
  {
    "caption": "C-EH3K9me2 levels on heterochromatin‐adjacent genes assessed by ChIP-PCR in swi6+, swi6∆, and swi6‐L315E (CSD dimerization mutant) (C), swi6‐W104A (H3K9me2 binding mutant) (D), and epe1∆ (E) cells. Enrichments over clr4∆ are normalized to adh1+. Average fold enrichment with s.d. is shown for three (C and E) or four (D) independent experiments. P‐values were generated by the Student's t‐test (two‐tailed distribution, two‐sample, unequal variance).",
    "ncbi_link": "adh1: 2538902
clr4: 2540825
epe1: 2539481
swi6: 2541633"
  },
  {
    "caption": "sRNA reads mapping to centromere 1 in swi6+ (green) and swi6∆ (blue) cells. The dashed red box highlights the loss of brdrRNAs at the IRC1R in the absence of Swi6. Centromeric repeat elements and the central core are indicated. Counts were normalized to the library size. Asterisks denote tRNA fragments. Note that tRNA genes flank IRC3 (Fig EV4) but not IRC1R.",
    "ncbi_link": "IRC1R: 
IRC3: 851932
swi6: 2541633
Swi6: 2541633"
  },
  {
    "caption": "H3K9me2 levels on heterochromatin‐adjacent genes assessed by ChIP-PCR in swi6+, swi6∆, tas3 L479E, and tas3 L479E swi6∆ cells. Enrichments over clr4∆ are normalized to adh1+. Average fold enrichment with s.d. is shown for three independent experiments. P‐values were generated by Student's t‐test (two‐tailed distribution, two‐sample, unequal variance).",
    "ncbi_link": "adh1: 2538902
clr4: 2540825
swi6: 2541633
tas3: 2540735"
  },
  {
    "caption": "(A-E) GFP-pho8Δ60-expressing wild-type (WT), atg5Δ, atg7Δ, and atg5Δpep4Δ cells were starved (A) or treated with AmphoB (B-E) and subjected to western blotting. Cells were treated with 2.5 µg/ml AmphoB for the indicated time (B) or with the indicated doses for 24 hr (C-E). Generation of free GFP was a marker of proteolysis.",
    "ncbi_link": "atg5: 855954
atg7: 856576
pep4: 855949"
  },
  {
    "caption": "(F) GFP-pho8Δ60- and Pep4-mRFP-expressing atg5Δ cells were cultured with (AmphoB) or without (NT) AmphoB (2.5 µg/ml, 24 hr), and localization of GFP-pho8Δ60 and Pep4-mRFP was observed by confocal microscopy. Arrowheads indicate the cells in which GFP-pho8Δ60 was delivered to the vacuoles. Scale bars = 2 µm.",
    "ncbi_link": "atg5: 855954"
  },
  {
    "caption": "(G, H) Accumulation of autophagic body (AB)-like structures by AmphoB in atg5Δpep4Δ cells. pep4Δ and atg5Δpep4Δ cells were starved for 3 hr or treated with AmphoB (2.5 µg/ml, 24 hr). Scale bars = 2 µm. Cells containing AB-like structures were counted under phase-contrast microscopy. Representative images (G) and the percentage of cells with AB-like structures (H) are shown. *p < 0.01 vs the value of pep4Δ cells. (I-K) Induction of AB-like structures in atg5Δpep4Δ cells treated with AmphoB (2.5 µg/ml, 24 hr). Representative images of quick-frozen replicas (I) and thin section of the frozen-substituted material (J) are shown.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(G, H) Accumulation of autophagic body (AB)-like structures by AmphoB in atg5Δpep4Δ cells. pep4Δ and atg5Δpep4Δ cells were starved for 3 hr or treated with AmphoB (2.5 µg/ml, 24 hr). Scale bars = 2 µm. Cells containing AB-like structures were counted under phase-contrast microscopy. Representative images (G) and the percentage of cells with AB-like structures (H) are shown. *p < 0.01 vs the value of pep4Δ cells. (I-K) Induction of AB-like structures in atg5Δpep4Δ cells treated with AmphoB (2.5 µg/ml, 24 hr). Representative images of quick-frozen replicas (I) and thin section of the frozen-substituted material (J) are shown.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(A-D) Generation of Golgi stacks by AmphoB. Stacked Golgicisternae are observed in quick-frozen replicas (A-C) and substituted thin section (D) of atg5Δpep4Δ cells treated with AmphoB (2.5 µg/ml) for the indicated time. (A) Scale bar = 1 µm. (B) The magnified image shows the area indicated by the square in (A). Scale bar = 0.5 µm. (C, D) A representative Golgi stack with four cisternae is shown. Scale bar = 0.5 µm.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(H, I) The scene that AP-like structure was fused with vacuole. A magnified image of (H) is shown in (I). In atg5Δpep4Δ cells treated with AmphoB (2.5 µg/ml, 24 hr), outer membrane of AP-like structure (red arrows) was fused with vacuolar membrane (blue arrows). Inner membranes of AP-like structure (yellow arrowheads) were entered into the vacuoles to become AB-like structure. Green arrows indicate the membrane fusion site. Scale bars = 0.5 µm (H) and 0.2 µm (I).",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(K) Translocation of the trans-Golgi protein to the vacuolar membrane induced by AmphoB treatment. GFP-Sft2-expressing atg5Δ cells (trans-Golgi marker protein) were incubated with or without AmphoB (2.5 µg/ml, 24 hr), and localization of GFP-Sft2 was assessed by confocal microscopy. Arrowhead indicates the GFP signal on the vacuolar membrane. Scale bars = 2 µm.",
    "ncbi_link": "atg5: 855954"
  },
  {
    "caption": "(L-O) Grh1 and Gvp36 involvement in AmphoB-induced autophagy-like proteolysis. (L, M) Representative electron microscopy images of grh1Δatg5Δpep4Δ (L) and gvp36Δatg5Δpep4Δ cells (M) treated with AmphoB (2.5 µg/ml, 24 hr). AP-like and AB-like structures were absent. (L) A unilamellar Golgi cisterna was observed in the cytoplasm (dotted square). Scale bar = 1 µm. (M) Formation of a Golgi stack, but not Golgi curvature, was observed (dotted square). Bar = 0.5 µm.",
    "ncbi_link": "atg5: 855954
Grh1: 852129
grh1: 852129
Gvp36: 854770
gvp36: 854770
pep4: 855949"
  },
  {
    "caption": "(L-O) Grh1 and Gvp36 involvement in AmphoB-induced autophagy-like proteolysis. (N) Indicated cells were treated with AmphoB for 24 hr and the number of cells containing AB-like structures was counted by phase-contrast microscopy. *p < 0.01 vs the value of atg5Δpep4Δ cells.",
    "ncbi_link": "atg5: 855954
Grh1: 852129
Gvp36: 854770
pep4: 855949"
  },
  {
    "caption": "(L-O) Grh1 and Gvp36 involvement in AmphoB-induced autophagy-like proteolysis. (O) GFP-pho8Δ60-expressing atg5Δ, grh1Δatg5Δ and gvp36Δatg5Δ cells were cultured with or without AmphoB (2.5 µg/ml, 24 hr) and subjected to western blotting for GFP. An unidentified band at 32kD (asterisk) is non-specific band because it was present in Pep4-lacking grh1Δatg5Δ cells.",
    "ncbi_link": "atg5: 855954
Grh1: 852129
grh1: 852129
Gvp36: 854770
gvp36: 854770"
  },
  {
    "caption": "(A) Localization of cellular PI(4)P. GFP-2xPHOsh2-expressing atg5Δ, sac1-23/atg5Δ, and pik1-83/atg5Δ cells were incubated with or without AmphoB (2.5 µg/ml) for 6 hr at 37 °C, and their localization was observed by confocal microscopy. Scale bars = 2 µm.",
    "ncbi_link": "atg5: 855954
pik1: 855454
sac1: 853668"
  },
  {
    "caption": "(E−H) Induction of GOMED by the deletion of Golgi PI(4) kinase. (E) Indicated cells were incubated at 37 °C (temperature shift) for 6 hr, and cells containing AB-like structures were counted by phase-contrast microscopy. *p < 0.01 vs the value of atg5Δpep4Δ cells.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(E−H) Induction of GOMED by the deletion of Golgi PI(4) kinase. (F) Representative electron microscopy image of pik1-83/atg5Δpep4Δ cells at 3 hr after temperature shift. AP-like structure (arrow) and AB-like structures were generated. Scale bar = 0.2 µm. (G) The number of AP-like and AB-like structures was counted using EM images. Error bars indicate s.e.m. (atg5Δpep4Δ cells at 37 °C: n = 54 and pik1-83/atg5Δpep4Δ cells at 37 °C: n = 63). *p < 0.01 vs the value of atg5Δpep4Δ cells.",
    "ncbi_link": "atg5: 855954
pep4: 855949
pik1: 855454"
  },
  {
    "caption": "(E−H) Induction of GOMED by the deletion of Golgi PI(4) kinase. (H) Sec7-HA-expressing pik1-83/atg5Δ cells were incubated at 37 °C (temperature shift) for 3 hr, and freeze replica immunolabelling was performed as described in Methods. Sec7-HA-positive signals (labelled with 15 nm gold particle) were observed on the surface membrane of AP-like structure and Golgi membrane. Scale bar = 0.1 µm.",
    "ncbi_link": "atg5: 855954
pik1: 855454"
  },
  {
    "caption": "(I−L) Genetic (I, J) and pharmacological (K, L) alterations in anterograde trafficking from the Golgi are required for GOMED. (I) Indicated cells were incubated at 37 °C (temperature switch) for 3 hr, and the cells containing AB-like structures were counted by phase-contrast microscopy. *p < 0.01 vs the value of atg5Δpep4Δ cells.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "Genetic (I, J) and pharmacological (K, L) alterations in anterograde trafficking from the Golgi are required for GOMED. (K, L) atg5Δpep4Δ cells were treated with (CBM) or without (NT) CBM (1 mM, 3 hr), and cells containing AB-like structures were counted by phase-contrast microscopy (K). * p < 0.01 vs the value of NT.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "Genetic (I, J) and pharmacological (K, L) alterations in anterograde trafficking from the Golgi are required for GOMED. (K, L) atg5Δpep4Δ cells were treated with (CBM) or without (NT) CBM (1 mM, 3 hr). Cells were also observed using EM (L). AB-like structures were observed. Scale bar = 0.5 µm.",
    "ncbi_link": "atg5: 855954
pep4: 855949"
  },
  {
    "caption": "(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (A, B) EM analysis revealed the formation of AP-like and AL-like structures. Atg5 KO MEFs were treated with CBM (2 mM) for 3 hr. A representative low-magnification image (A) and high-magnification images (B) are shown. Scale bar = 1 µm (A) and 0.2 µm (B). The arrowheads and arrows indicate AL-like and AP-like structures, respectively.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (C-F) Involvement of Golgi membranes in the generation of AL-like structures. (C) CLEM analysis of mCherry-syntaxin 6-expressing Atg5 KO MEFs. Cells were treated with CBM (2 mM) for 24 hr and observed using fluorescence and electron microscopy. mCherry-syntaxin 6puncta merged with the AL-like structures. Scale bar = 5 µm. \"N\" indicates nucleus. A magnified image of the dashed square is shown in the inset. Scale bars = 2 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (C-F) Involvement of Golgi membranes in the generation of AL-like structures. (D, E) Requirement of Grasp65 in the generation of AL-like structures. Atg5 KO and Grasp65-silenced Atg5 KO MEFs were treated without (NT) or with CBM (2 mM) for the indicated times followed by immunostaining with an anti-Lamp2 antibody. Representative images (at 24 h) are shown in (D). Scale bars = 5 µm. A magnified image of the dashed square is shown in the inset. Scale bars = 1 µm. CBM induced large ring-like Lamp2 fluorescence. (E) Percentages of cells with large ring-like Lamp2 immunofluorescence (mean ± s.e.m., n = 4). *p < 0.01 vs the value of Atg5 KO MEF.",
    "ncbi_link": "Atg5: 11793
Grasp65: 74498"
  },
  {
    "caption": "(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (C-F) Involvement of Golgi membranes in the generation of AL-like structures. (F) Colocalization of Lamp2 and GFP-syntaxin 6 in CBM-treated Atg5 KO MEFs. GFP-syntaxin 6-expressing Atg5 KO MEFs were treated with (CBM) or without (NT) CBM (2 mM) for 6 hr and immunostained with an anti-Lamp2 antibody. The ring-like Lamp2 fluorescence merged with the signal for syntaxin 6. Scale bar = 5 µm. A magnified image of the dashed square is shown in the inset. Scale bars = 2 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(G) The monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP) tandem protein assay revealed the induction of GOMED. Atg5 KO MEFs stably expressing tandem mRFP-GFP were incubated without (no treatment) or with CBM (2 mM) for 24 hr. Red signals indicate acidic compartments. Lysosomes were counterstained with an anti-Lamp2 antibody (cyan). Scale bars = 5 µm. Regions of interest (ROI) are indicated by dashed squares. Arrowheads indicate GOMED structure. Scale bars = 2 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A−I) Induction of GOMED in Atg5 KO MEFs by CBM treatment. (H, I) Degradation of GFP-fused proteins indicated the induction of GOMED. Atg5 KO MEFs stably expressing VSVG-GFP (H) or M6PR-GFP (I) were incubated with CBM (5 mM) for the indicated times. Cell lysates were subjected to immunoblotting with the anti-GFP antibody.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(J−M) Genetic induction of GOMED in Atg5 KO MEFs. Atg5 KO MEFs were treated with the indicated small interfering (si)RNAs for 24 hr and GOMED was assessed by EM (J-L). Representative images are shown in (J, K). Arrows indicate AL-like structures. Scale bars = 2 µm. (L) The number of AP-like and AL-like structures was calculated from the EM images of cells treated with the indicated siRNAs. Error bars indicate s.e.m. (siControl: n = 23, siPI4k2α + siPI4k3β: n = 20, siArfaptin1: n = 20). *p < 0.01 vs the value of siControl.",
    "ncbi_link": "PI4k3β: 
Arfaptin1: 99889
Atg5: 11793
PI4k2α: 84095"
  },
  {
    "caption": "(J−M) Genetic induction of GOMED in Atg5 KO MEFs. Atg5 KO MEFs were treated with the indicated small interfering (si)RNAs for 24 hr and GOMED was assessed by the mRFP-GFP tandem protein assay (M). (M) The same experiments as in (G) were performed using cells treated with the indicated siRNAs. Representative images are shown. Arrowheads indicate GOMED structure. Scale bars = 5 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A) Suppression of insulin secretion in Atg5 knockout (KO) MIN6 cells after glucose deprivation. Atg5 KO MIN6 cells were incubated with normal culture medium (NT) or glucose-depleted medium for 1 hr. The amount of secreted insulin is expressed as the percentage of that of the untreated control (NT) (mean ± s.e.m, n = 3). *p < 0.01 vs the value of NT.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(B, C) EM analysis revealed the induction of GOMED structures. Atg5 KO MIN6 cells were subjected to glucose deprivation for 1 hr. Representative images are shown. The white arrow and black arrows indicate the AP-like structure and insulinvesicles, respectively. Scale bars = 0.2 µm. (D) The number of AP-like and AL-like structures was calculated from the EM images of cells left untreated (NT) or subjected to glucose deprivation. Error bars indicate s.e.m. (NT: n = 17, glucose deprivation: n = 84). *p < 0.01 and #p < 0.05 vs the value of NT.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(E) Involvement of Golgi membrane in the generation of GOMED. Lamp1-GFP/mCherry-Syntaxin 6-expressing Atg5 KO MIN6 cells were subjected to glucose deprivation, and analysed by TEM and confocal microscopy. CLEM analysis revealed that AL-like structures (arrows) merged with Lamp1-GFP fluorescence and Syntaxin 6 fluorescence. Scale bars = 5 µm. A magnified image of the dashed square is shown in the inset. Scale bars = 2 µm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(F) GOMED-mediated degradation of (pro)insulin by glucose deprivation of Atg5 KO MIN6 cells. Atg5 KO MIN6 cells were incubated in glucose-depleted medium in the absence or presence of bafilomycin A1 (10 nM) for the indicated times. The cell lysates were then subjected to immunoblot analysis using an anti-(pro)insulin antibody.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(G) Immunofluorescence analysis of (pro)insulin and Lamp2. Atg5 KO MIN6 cells were left untreated (NT) or subjected to glucose deprivation for 1 hr in the presence of E64d (25 µM) or bafilomycin A1 (10 nM), and were stained with anti-(pro)insulin and anti-Lamp2 (lysosomal marker) antibodies and observed by fluorescence microscopy. Scale bar = 1 µm. Arrowheads indicate the colocalization of (pro)insulin with GOMED structures.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A−D) EM analysis demonstrated the induction of GOMED. Primary Atg7 KO β-cells were subjected to glucose deprivation for 1 hr. A representative AP-like structure containing insulingranule is shown in (A). An AL-like structure containing insulingranules is shown in (B). Scale bars = 0.2 µm.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(A−D) EM analysis demonstrated the induction of GOMED. Primary Atg7 KO β-cells were subjected to glucose deprivation for 1 hr. (C, D) GOMED structures containing Golgi vesicles. An AP-like structure containing multiple Golgi vesicles (arrows) (C) and an AL-like structure fusing with a lysosome (arrowhead) (D) are shown. Scale bar = 0.5 µm. A magnified image of the dashed rectangle is shown in the inset. Scale bar = 0.2 µm. AP-like structure contained double-membrane.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(E) The total number of AL-like structure was calculated from the EM images of WT and Atg7 KO β-cells after glucose deprivation. Error bars indicate s.e.m. (n = 46−163). *p < 0.01 and #p < 0.05 vs the value of 0 min.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(F) The total number of GOMED structure was calculated from the EM images of Atg7 KO β-cells after glucose deprivation in the absence or presence of bafilomycin A1 (10 nM). Error bars indicate s.e.m. (n = 109−116). *p < 0.01 vs the value of 60 min.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(G−J) EM analysis showed the induction of mitophagy. WT and Atg7 KO β-cells were subjected to glucose deprivation for 1 hr. Representative images showing mitophagy in Atg7 KO β-cells are shown in (G). Arrowhead (G) indicates mitophagy. Scale bars = 0.5 µm. (H, J) The number of structures representative of mitophagy (H) per cell was calculated from the EM images of β-cells after glucose depletion. Error bars indicate s.e.m. (n = 46−163). *p < 0.01 and #p < 0.05 vs the value of 0 min.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(G−J) EM analysis showed the induction of crinophagy/SINGD. WT and Atg7 KO β-cells were subjected to glucose deprivation for 1 hr. Representative images showing crinophagy/SINGD in WT β-cells are shown in (I). White arrow (I) indicates crinophagy/SINGD. Arrows indicate insulingranules (I). Scale bars = 0.5 µm. (H, J) The number of structures representative of crinophagy/SINGD (J) per cell was calculated from the EM images of β-cells after glucose depletion. Error bars indicate s.e.m. (n = 46−163). *p < 0.01 and #p < 0.05 vs the value of 0 min.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(K) The number of (pro)insulingranule-containing AL-like structure was calculated from the EM images of wild-type (WT) and Atg7 KO β-cells after glucose deprivation. Error bars indicate s.e.m. (n = 46−163). *p < 0.01 and #p < 0.05 vs the value of 0 min.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "Overexpression of WT OGT, but not catalytic-inactive OGT mutant, increased the O-GlcNAc levels of TDP-43. OGT protein levels were examined by immunoblotting.   Quantification of (G).   ",
    "ncbi_link": "OGT: 8473"
  },
  {
    "caption": "SDS-soluble and insoluble fractions were isolated from SH-SY5Y cells expressing WT or catalytic-inactive mutant OGT treated with 20 μM EA, and the fractions were analyzed by immunoblotting. Quantification of (F).",
    "ncbi_link": "OGT: 8473"
  },
  {
    "caption": "Cells expressing the indicated forms of GFP-TDP-43 were subjected to immunoprecipitation, and the O-GlcNAcylated levels of TDP-43 were examined.   Quantification of (G).   ",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "CFTR splicing assay was performed in cells with knockdown of either OGT, TDP-43, or combination. ACTB levels served as loading controls (top panel). The indicated protein levels were examined by immunoblotting (bottom panel).",
    "ncbi_link": "ACTB: 
CFTR: 12638
OGT: 108155
TDP-43: 230908"
  },
  {
    "caption": "CFTR splicing assay was examined in siTDP-43 cells overexpressing the WT or mutant OGT by PCR analysis. ACTB levels served as loading controls (top panel). Various protein levels were examined by immunoblotting (bottom panel).",
    "ncbi_link": "ACTB: 
CFTR: 12638
OGT: 8473
TDP-43: 230908"
  },
  {
    "caption": "Representative PCR analysis to examine expression levels of the spliced mRNA isoform containing exon 2a of STMN2 in SH-SY5Y cells with the indicated constructs (top panel). TDP-43 protein levels were examined by immunoblotting (bottom panel).",
    "ncbi_link": "STMN2: 11075"
  },
  {
    "caption": "C Fraction of expressed genes (genes with non-zero counts in DESeq2) were calculated which exhibit individual or combinations of differential gene expression (DGE), differential transcript usage (DTU) and/or  alternative splicing   (AS) events in HEK293  and HeLa  WT cells overexpressing UPF3A  using the respective computational analysis (cutoffs are indicated). AS and DTU events were collapsed on the gene level. For DGE, p-values were calculated by DESeq2 using a two-sided Wald test and corrected for multiple testing using the Benjamini-Hochberg method. For DTU, p-values were calculated by IsoformSwitchAnalyzeR (ISAR) using a DEXSeq-based test and corrected for multiple testing using the Benjamini-Hochberg method. For AS, p-values were calculated by LeafCutter using an asymptotic Chi-squared distribution and corrected for multiple testing using the Benjamini-Hochberg method.",
    "ncbi_link": "UPF3A: 65110"
  },
  {
    "caption": "E Read coverage of SMG5 from WT HEK293  and HeLa RNA-seq data with or without induced UPF3A  overexpression shown as Integrative Genomics Viewer (IGV) snapshot. Differential gene expression (from DESeq2) is indicated as log2 fold change (log2FC) on the right. Schematic representation of the protein coding transcript below.",
    "ncbi_link": "SMG5: 23381
UPF3A: 65110"
  },
  {
    "caption": "A Western blot  analysis of WT and UPF3A KO cells (clones 4, 14 and 20) with the indicated siRNA treatments (n=1). UPF3A and UPF3B protein levels were detected, Tubulin  serves as control. The asterisk indicates unspecific bands.",
    "ncbi_link": "UPF3A: 65110"
  },
  {
    "caption": "B Quantitative RT-PCR of the indicated cell lines treated with the indicated siRNAs for 2 or 6 days. For RSRC2  and SRSF2  the ratio of NMD isoform to canonical isoform was calculated. ZFAS1 expression  was normalized to C1orf43 reference. Data points and means are plotted as log2 fold change (log2FC) (n=3 for RSRC2  and SRSF2, n=4 for ZFAS1).",
    "ncbi_link": "C1orf43: 25912
RSRC2: 65117
SRSF2: 6427
ZFAS1: 441951"
  },
  {
    "caption": "D,E Volcano plots showing the differential gene expression analyses from the indicated  RNA-Seq datasets (D UPF3A  KO clone 14, E UPF3A  KO clone 20). The log2 fold change is plotted against the -log10 adjusted p-value (adj. p-value). P-values were calculated by DESeq2 using a two-sided Wald test and corrected for multiple testing using the Benjamini-Hochberg method",
    "ncbi_link": "UPF3A: 65110"
  },
  {
    "caption": "A  Western blot  analysis of WT and UPF3B  KO cells (clones 90 and 91) combined with the indicated knockdowns (n=1). UPF3A  and UPF3B  (AK-141) protein levels were detected, Tubulin  serves as control. Protein levels of UPF3A  were quantified, normalized to tubulin  expression, and shown as datapoints and mean. Fold-changes of relevant conditions are shown. The asterisk indicates unspecific bands.",
    "ncbi_link": "UPF3B: 65109"
  },
  {
    "caption": "B Quantitative RT-PCR of the indicated cell lines with the indicated knockdowns. For RSRC2  and SRSF2  the ratio of NMD isoform to canonical isoform was calculated. Data points and means are plotted as log2 fold change (log2FC, n=3).",
    "ncbi_link": "RSRC2: 65117
SRSF2: 6427"
  },
  {
    "caption": "A Western blot  analysis of WT, UPF3B  KO and UPF3A-UPF3B  double KO cells (clones 1 and 2) (n=1). UPF3A  and UPF3B protein levels were detected, Tubulin  serves as control. The asterisk indicates unspecific bands.",
    "ncbi_link": "UPF3A: 65110
UPF3B: 65109"
  },
  {
    "caption": "C Quantitative RT-PCR  of the indicated samples with the indicated KDs. For RSRC2  and SRSF2  the ratio of NMD isoform to canonical isoform was calculated. ZFAS1 expression  was normalized to C1orf43  reference. Data points and means are plotted as log2 fold change (log2FC, n=3).",
    "ncbi_link": "C1orf43: 25912
RSRC2: 65117
SRSF2: 6427
ZFAS1: 441951"
  },
  {
    "caption": "E Northern blot  analysis of globin  reporter and xrFrag. Ethidium bromide stained 28S and 18S rRNAs are shown as controls. Quantification results are shown as data points and mean (n=3).",
    "ncbi_link": "18S rRNAs: 
28S: 
globin: 3043"
  },
  {
    "caption": "A-C Volcano plots of label free mass spectrometry-based analysis of the interaction  partners of UPF2  in WT cells treated with control siRNAs and the UPF3B KO clone 90 and dKO clone 1 both treated with siRNAs targeting UPF3B  (n = 4 biologically independent samples). (A) FLAG-UPF2   in WT against FLAG-GST   control in WT cells, (B) UPF2   in 3B KO cells against FLAG   control in WT cells, (C) UPF2   in dKO cells against FLAG   control in WT cells. Points labeled in purple indicate NMD factors; points labeled in turquoise indicate EJC components. Cut offs: Log2 fold change ≥ 0",
    "ncbi_link": "FLAG: 
GST: 
UPF2: 26019
UPF3B: 65109"
  },
  {
    "caption": "E Representative  Western blot  after FLAG co-immunoprecipitation (IP) of FLAG-tagged GST  (control) or UPF3B  WT and single mutant constructs in UPF3B  KO cells (n = 3).",
    "ncbi_link": "FLAG: 
GST: 
UPF3B: 65109"
  },
  {
    "caption": "F Western blot  analysis of WT and UPF3B  KO clone 90 with Luciferase  and UPF3A  KDs respectively. Monitored expression of the FLAG-tagged UPF3B  rescue construct shown in (D). Rescue construct protein levels were detected with anti-FLAG and anti-UPF3B  (AK-141) antibodies. Tubulin serves as control (n=1).",
    "ncbi_link": "Luciferase: 
UPF3A: 65110
UPF3B: 65109"
  },
  {
    "caption": "G  Quantitative RT-PCR of the samples from (F). For RSRC2 and SRSF2  the ratio of NMD isoform to canonical isoform was calculated. ZFAS1 expression  was normalized to C1orf43  reference. Data points and means are plotted as log2 fold change (log2FC, n=3).",
    "ncbi_link": "C1orf43: 25912
RSRC2: 65117
SRSF2: 6427
ZFAS1: 441951"
  },
  {
    "caption": "B Western blot  analysis of WT and UPF3B  KO clone 90 with Luciferase  and UPF3A KDs respectively. Monitored expression of the FLAG-tagged  UPF3A and  UPF3B rescue construct shown in (A). Rescue construct protein levels were detected with anti-FLAG, anti-UPF3A  and anti-UPF3B  (AK-141) antibodies. Tubulin  serves as control (n=1). The asterisk indicates unspecific bands.",
    "ncbi_link": "FLAG: 
Luciferase: 
UPF3A: 65110
UPF3B: 65109"
  },
  {
    "caption": "C Quantitative RT-PCR of the samples from (B). For RSRC2  and SRSF2  the ratio of NMD isoform to canonical isoform was calculated. Data points and means are plotted as log2 fold change (log2FC) (n=3).",
    "ncbi_link": "RSRC2: 65117
SRSF2: 6427"
  },
  {
    "caption": "Immunohistochemistry performed on 12 month-old THY-Tau22 mice showing AT100-positive neurons (green), CBP-positive nuclei (red) and DAPI-stained nuclei (blue) in the CA1 region of the dorsal hippocampus. A representative image is shown with a focus. Scale bars: 40µm and 20µm as noted. (n=5 mice). Arrows depict neurons bearing neurofibrillary tangles and do not display CBP immunostaining. The star depicts a ghost tangle (AT100-positive neuron and no nucleus)",
    "ncbi_link": "Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Western blot analyses perfomed in the dorsal hippocampus of 12 month-old THY-Tau22 mice compared to age-matched controls. NeuN, actin, tubulin and total H2B levels are not changed. Phosphorylated tau on serine 404 (Tau-Ph404) attest for samples from tauopathic mice. Quantification represents the ration of the protein level detected on the total amount of proteins on the membranes, with WT arbitrarily set at 1 (fold induction). Bar graphs are mean ± SEM. n=5-7/group as noted, multiple t tests, CBP * p=0.003 and GFAP **p=0.0001 for THY-Tau vs. WT mice",
    "ncbi_link": "Tau: 4137
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "RNA-sequencing data performed in the hippocampus of 8 month-old mice. Functional analyses (DAVID GOTERM) performed on significantly deregulated genes in THY-Tau22 mice compared to WT mice. Representative genes are presented below. |log2 Fold Change| > 0.2; * indicates FDR<0.05. IEG, Immediate Early Genes. Predicted promoter motif (right) analyses performed with GREAT. Groups: WT mice (n=3), THY-Tau22 mice (n=2)",
    "ncbi_link": "Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Long-term spatial memory testing: Mice were injected 3 times (1 per week) with Vehicle (WT mice saline, WT VEH, n=17), Vehicle (THY-Tau22 mice CSP, 500 μg /mouse, TAU VEH, n=10) or Molecule (THY-Tau22 mice CSP-TTK21, 500 μg/mice TAU MOL, n=13) before training of spatial memory in the Morris water maze (MWM); retention (Probe test) was tested 10 days after the last training session. Acquisition (Escape latencies, seconds) and retention performances (Time in target quadrant, seconds) are shown for the 3 groups of mice. All groups of mice displayed significant acquisition of the platform location (Day effect, F(4,148)= 26.45, p<0.001; Group and Group X Day effects, ns), but only TAU VEH exhibited impaired retention. CSP-TTK21 treatment fully restored the ability of THY-Tau22 mice to remember the platform location. Bar graphs are mean ± SEM. Student's t test to a constant value, # when compared to random (dotted line, 15sec) WT VEH, t(16)=4.6323, #p=0.0002; TAU VEH, t(9)=0.3606, p=0.7267; TAU MOL, t(12)=3.945, #p=0.0019. One-way ANOVA; F(2,37)= 3.55; p= 0.03; * in the different comparisons: TAU MOL vs. TAU VEH, *p=0.0166; WT VEH vs. TAU VEH, *p= 0.040; TAU MOL vs WT VEH, non significant p=0.437). TQ, Target Quadrant; O, Other, corresponds to the mean of the 3 other quadrants",
    "ncbi_link": "TAU: 4137
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "The timeline of GFP-lentivirus and CSP or CSP-TTK21 (one injection, 500 μg/mouse) injection is shown. (Left) The total number of spines was significantly decreased in TAU VEH compared to WT VEH mice. TAU MOL hippocampi showed a significant increase in the total number of spines compared to TAU VEH (One-way ANOVA p=0.0011, post hoc Holm Sidak's multiple comparisons test F(2,243) = 7.03; WT VEH vs. TAU VEH, p < 0.0009; TAU MOL vs. TAU VEH, p=0.0455). (Middle) Based on spine type, the number of head spines (Mushrooms, thins) was significantly lower in both TAU VEH and TAU MOL than in WT VEH controls (One-way ANOVA p=0.0018, post hoc Holm Sidak's multiple comparisons test F(2,243) = 6.467; WT VEH vs. TAU VEH, p=0.0013; WT VEH vs. TAU MOL, p=0.0272. Stubby spine density was significantly increased in TAU MOL compared to TAU VEH mice (One-way ANOVA F(2,243) = 4.311, p = 0.0145, post hoc Holm Sidak's multiple comparisons test: TAU MOL vs. TAU VEH, p=0.0109), as the number of filopodia (One-way ANOVA F(2,243) = 3.845, p = 0.0227, post hoc Holm Sidak's multiple comparisons test TAU MOL vs. TAU VEH, p=0.0179). (Right) Typical images are presented showing a dendrite fragment for each condition. White arrowhead depicts stubby spines. Scale bar, 2 μm. Number of dendritc segments: WT VEH, n=67; TAU VEH, n=93, TAU MOL, n=87; Number of neurons: WT VEH, n=20; TAU VEH, n=28, TAU MOL, n=16; Number of mice: WT VEH, n=2; TAU VEH, n=3, TAU MOL, n=3 ",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "CSP-TTK21 injection into THY-Tau22 mice rescues mature dendritic spines formation in response to learning. (Top left) The time line of injections is shown: Mice were injected 3 times (1 per week) with Vehicle (WT mice, WT VEH, NaCl 0.9%), Vehicle (THY-Tau22 mice (TAU VEH), CSP 500 μg /mouse) or Molecule (THY-Tau22 mice (TAU MOL), 500 μg/mice) and either trained over a 4-day acquisition period in the MWM ("learning" group) or left in their home cage ("basal" group). Mushroom-shaped spines were counted in dorsal CA1, four days post-training. (Bottom left) The number of mature spines was significantly increased by learning in WT VEH and TAU MOL mice. Bar graphs are mean ± SEM. (Two-way ANOVA; Learning effect, F(1, 139)=54.18; p< 0.0001; ### post hoc Holm Sidak's multiple comparisons test: Learning vs. Basal in WT VEH (p=0.0001) and in TAU MOL mice; (p=0.0001). After learning, WT VEH and TAU MOL mice displayed significantly higher number of mature spines than TAU VEH mice (Genotype X Treatment effect, F(2,139)= 9.704; p=0.0001; *** post hoc Holm Sidak's multiple comparisons test: TAU MOL vs. TAU VEH (p=0.0001), WT VEH vs. TAU VEH (p=0.0001). (Right) Typical examples of a dendritic fragment bearing mushroom spines (arrows) are shown for each sub-group in response to learning. Number of dendritc segments: Learning: WT VEH, n=27; TAU VEH, n=27, TAU MOL, n=30; WT VEH_HC, n=27; Number of mice: WT VEH, n=3; TAU VEH, n=3, TAU MOL, n=3. Basal: WT VEH, n=27; TAU VEH, n=7, TAU MOL, n=15; Number of mice: WT VEH, n=3; TAU VEH, n=3, TAU MOL, n=2 ",
    "ncbi_link": "TAU: 4137
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Mice were injected 3 times (1 per week) with saline (WT VEH), CSP (Vehicle, VEH) or CSP-TTK21 (Molecule, MOL) (500 μg/mice; THY-Tau22 mice (TAU) before euthanasia. Long Term Depression measurements were performed on hippocampal slices. (Top left) Examples of analog traces recorded 10 min before (a) and 55 min after LTD induction (b; dotted line) in the three groups of mice. (Bottom left) Time course of LTD; LTD is expressed as a percent change in fEPSP (field excitatory postsynaptic potentials) slope over time. After the 20-min baseline recording, a low-frequency stimulation (LFS, 2Hz for 10 min) was applied (arrow). Recording was stopped during the 10-min conditioning stimulation and resumed after completion of LFS. LFS induced a strong depression of the fEPSP slope, which recovered partially to reach a stable level of depression about 20 min after stimulation. (Right) Average depression measured in the last 10 min of LTD. LTD was significantly different in TAU VEH (88.4 ± 4.1% of the baseline, n=10) compared to controls (WT VEH, 71.1 ± 4.4%, n=9) (F(1,17)=8.8, p=0.008). CSP-TTK21 treatment restored LTD to control levels (64.9 ± 5.2%, n=10) (WT VEH vs. TAU MOL: F(1,17)=0.83, p=0.37, ns; TAU VEH vs. TAU MOL: F(1,18)=13.2. p=0.0019). Bar graphs are mean ± SEM",
    "ncbi_link": "TAU: 4137
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Volcano plot showing that 2756 genes are differentially regulated between THY-Tau22 and WT mice during learning. The log2(Fold-Change) was estimated by DESeq2. FDR<0.05 and |log2 Fold Change| > 0.2. Red dots correspond to genes with adjusted p-value <0.05. Numbers in the corners represent the number of down-regulated (left) and up-regulated (right) genes. C Heatmap representing expression of z-score of the 2756 deregulated genes in all experimental conditions. Color-coding was performed according to the z-score of the normalized reads counts divided by gene length. Clustering was performed using the Unweighted Pair Group Method with Arithmetic mean method and the Pearson"s distance. Groups: WT VEH_HC (n=3), WT VEH (n=2); TAU VEH (n=2); TAU MOL",
    "ncbi_link": "TAU: 4137
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Volcano plot showing that 1756 genes are differentially regulated between treated-THY-Tau22 and WT mice during learning. Same parameters as in B",
    "ncbi_link": "Tau22: 4137
THY: 21838"
  },
  {
    "caption": "F, G Volcano plots showing differentially regulated genes by the molecule in THY-Tau22 mice (F) and by learning in WT mice (G). Same parameters as in B",
    "ncbi_link": "Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Heatmap representing expression z-score of the 98 significantly over-expressed genes in the TAU MOL vs. TAU VEH comparison, for all experimental conditions. Color-coding was performed according to the z-score of the normalized reads counts divided by gene length. Clustering was performed using the Unweighted Pair Group Method with Arithmetic mean method and the Pearson"s dis",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "RNA-seq data showing expression of several immediate early genes (IEGs) : Nr4a1, Arc, Egr1, Dusp1, Fos and Junb. Most of the down-regulated IEGs in tauopathic compared to WT mice present a significant induction in THY-Tau22 mice after CSP-TTK21 injection. Adjusted p-values corresponding to p<0.05 are indicated by *, for WT VEH vs. WT VEH_HC, $ for TAU VEH vs. WT VEH and #, for TAU MOL vs. TAU VEH",
    "ncbi_link": "Arc: 11838
Dusp1: 19252
Egr1: 13653
Fos: 14281
Junb: 16477
TAU: 4137
Tau22: 4137
Nr4a1: 15370
THY: 21838"
  },
  {
    "caption": "RNA-seq data showing that CSP-TTK21 treatment of tauopathic mice restored the expression of plasticity/memory-relevant target genes : Klotho (Kl), and Neurotensin (Nts). Adjusted p values corresponding to p<0.05 are indicated by *, for WT VEH vs. WT VEH_HC, $ for TAU VEH vs. WT VEH and #, for TAU MOL vs. TAU VEH. F RT-qPCR validations performed in a different cohort of mice from the RNA-seq study (n=4-5/group). One-way ANOVA with uncorrected Fisher"s test. Klotho, Kl: F(3,16)=2.949, p=0.0643; * learning p=0.0145 for WT VEH vs. WT VEH_HC, $ pathology p=0.0395 for WT VEH vs. TAU VEH. Nts: F(3,14)=4.290, p=0.0241; $ pathology p=0.0036 for WT VEH vs. TAU VEH, # molecule p=0.0081 for TAU MOL vs. TA",
    "ncbi_link": "Kl: 16591
Klotho: 16591
TAU: 4137
Neurotensin: 67405
Nts: 67405"
  },
  {
    "caption": "Western blot for Klotho and Neurotensin expression in the different experimental conditions. Immunoblot results are shown (n=5/group). Bar graphs represent the quantification of the protein levels as percentage of the control group WT VEH_HC, arbitrarily set at 100%. Each detected protein was normalized to the corresponding amount of total proteins in the gels or the nitrocellulose membrane. Klotho and Neurotensin were further normalized to the level of actin. One-way ANOVA with uncorrected Fisher"s test. Klotho: F(3,16)=5.192, p=0.0107, * learning p=0.0117 for WT VEH vs. WT VEH_HC, $ pathology p=0.0027 for WT VEH vs. TAU VEH, # molecule p=0.0282 for TAU MOL vs. TAU VEH. Nts: F(3,16)=3.748, p=0.0326, $ pathology p=0.0200 for WT VEH vs. TAU VEH, # molecule p=0.0079 for TAU MOL vs. TA",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "A Functional annotation charts (Benjamini, p<0.05) using using DAVID (GOTERM_Cellular Component) perfomed on the 82 significantly down-regulated genes by CSP-TTK21 treatment in tauopathic mice (TAU MOL vs. TAU VEH), showing a significant association with neuronal terms. Significance is indicated as -log10(Benjamini p_value). B Heatmap representing expression z-score of the 82 significantly down-regulated genes in the TAU MOL vs. TAU VEH comparison, for all experimental conditions. Color-coding was performed according to the z-score of the normalized reads counts divided by gene length. Clustering was performed using the Unweighted Pair Group Method with Arithmetic mean method and the Pearson"s dis",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "C RNA-seq data showing expression of several genes belonging to « synapse » annotation (DAVID): Grik4, Homer3 and Sv2b, which are significantly down-regulated by CSPTTK21 treatment in THY-Tau22 mice. Adjusted p values corresponding to p<0.05 are indicated by * for WT VEH vs. WT VEH_HC, $ for TAU VEH vs. WT VEH and #, for TAU MOL vs. TAU VEH",
    "ncbi_link": "Grik4: 110637
Homer3: 26558
TAU: 4137
Tau22: 4137
Sv2b: 64176
THY: 21838"
  },
  {
    "caption": "Differentially regulated H2Bac peaks were analyzed with SICER and significant Fold Changes (FC>1; FDR<0.001) between comparisons are shown for the pathology (TAU VEH vs. WT VEH, blue) and the effect of the molecule (TAU MOL vs. TAU VEH, red). Fold Change is shown as log2 (Fold Change) (X-axis) and significance, as -log10(FDR) (Y-axis)",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "Mean H2Bac and H3K27ac profiles established with SeqMiner for the 1624 decreased peaks obtained in the comparison TAU VEH vs. WT VEH. H2Bac but not H3K27ac peaks show differential regulation",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "Time series Like plot. For every significant H2Bac decreased regions (1624) in WT VEH vs TAU VEH, normalized read counts were computed for each of the different conditions (WT VEH, TAU VEH, TAU MOL). Fold changes are all referring to WT VEH. Y-axis: Fold change. X-axis: Conditions",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "A Mean enrichment profiles performed with SeqMiner presenting the genomic distribution of H2Bac and H3K27ac reads obtained in ChIP-seq experiments in the different experimental groups, established along putative neuronal CBP enhancers (± 4Kb) (Kim et al., 2010). In the dorsal hippocampus, H2Bac levels are enriched at CBP enhancers in WT WEH (blue), decreased in tauopathic mice (TAU VEH, pink) and induced by CSP-TTK21 treatment (TAU MOL, green). B Mean profiles were separated in two sets of loci, including 17817 peaks highly enriched in H2Bac and showing a differential regulation in the experimental groups and 23331 peaks that were poorly enriched in H2Bac and not regulated",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "UCSC genome browser view of the c-fos genomic locus with H3K27ac ChIP-seq (blue), H2Bac ChIP-seq (green) and Input (black) signals. Blue shading indicates locations of the c-fos enhancers (Joo et al., 2016); gray shading indicates location of the promoter. Differential peaks were analyzed with SICER. This set of data shows that H2Bac levels were significantly decreased at e1 (FDR=1.95.10-08), e2 (FDR=0.0005) and e5 (FDR= 2.44.10-05) enhancers in THY-Tau22 compared to WT mice, and significantly enriched at e1 (FDR= 4.01.10-08) the regions encompassing e3, e4 and TSS (FDR=7.53.10-07) and e5 (FDR= 0.001) after CSP-TTK21 treatment. Expanded View Figure Legend",
    "ncbi_link": "c-fos: 14281
Tau22: 4137
THY: 21838"
  },
  {
    "caption": "Kaplan Meier plots representing the survival difference between SKCM patients stratified according to the 40% highest or lowest BNIP3 expression.",
    "ncbi_link": "BNIP3: 664"
  },
  {
    "caption": "Representative images of BNIP3 immunohistochemistry in TMAs containing (n=158) melanoma metastases and related Kaplan Meier plot of survival difference comparing melanoma patients with different BNIP3 histopathological scores. Scale bars represent 50µm.",
    "ncbi_link": "BNIP3: 664"
  },
  {
    "caption": "Growth curves of B16-F10 tumors generated with cells transduced with either empty vector (CntlKD), shRNA against BNIP3 (BNIP3KD) or ATG5 (ATG5KD) (n=7 per condition) and analyzed with a two-way ANOVA with Tukey's multiple comparisons test.",
    "ncbi_link": "ATG5: 11793
BNIP3: 12176"
  },
  {
    "caption": "Haematoxylin and eosin staining of sections representative of CntlKD, BNIP3KD or ATG5KD B16-F10 tumors. Necrotic areas are highlighted with an asterisk (*). Quantification of TUNEL+ tumor area (representing the fraction of dying/dead cell population) of CntlKD, BNIP3KD or ATG5KD B16-F10 tumors (n= 5 per condition). Quantification of the Ki67+ cells within the tumor area (representing the fraction of proliferative cell populations in non-necrotic areas) of CntlKD (n=7), BNIP3KD (n=6) and ATG5KD (n=8) B16-F10 tumors.",
    "ncbi_link": "ATG5: 11793
BNIP3: 12176"
  },
  {
    "caption": "Immunofluorescent staining for Ki67 (red) representative of CntlKD, BNIP3KD or ATG5KD B16-F10 tumor sections. Immunofluorescent staining for LC3B (orange granularity) representative of CntlKD, BNIP3KD or ATG5KD B16-F10 tumor sections. A zoomed-in area is shown in the lower-left corner.",
    "ncbi_link": "ATG5: 11793
BNIP3: 12176"
  },
  {
    "caption": "Confocal microscopy images of co-localization analysis of the BNIP3-proficient (shCntl, n=27 cells) or deficient (shBNIP3, n=31 cells) B16-F10 cells transiently transfected with GFP-LC3 and immunostained for TOMM20 (mitochondrial marker). Colocalization events of GFP-LC3 puncta (green) with TOMM20 (red) are highlighted with white arrows. The percentage of GFP-LC3 puncta colocalizing with TOMM20 was calculated in n cells from 3 biologically independent experiments and analyzed with Mann-Whitney's non-parametric test. Scale bars represent 10µm.",
    "ncbi_link": "BNIP3: 12176"
  },
  {
    "caption": "Glut1, Hk2, Pkm1, Pkm2, Pdk1, Mct1, Ldha, Ldhb and Mct4 transcript levels measured by qPCR from the corresponding B16-F10 cell lysates. Transcript expression is represented as the fold-change relative to their corresponding shCntl value. Heatmap shows the average values in each condition (n=4) and they were analyzed with a one-sample T-test only against shCntl, except for Glut1 shATG5 that was analyzed with a Wilcoxon rank test.",
    "ncbi_link": "ATG5: 11793
Hk2: 15277
Ldha: 16828
Ldhb: 16832
Mct1: 17236
Pdk1: 228026
Pkm1: 18746
Pkm2: 18746
Mct4: 80879
Glut1: 20525"
  },
  {
    "caption": "Immunoblot detection of Hydroxylated HIF-1α (HIF-1α-OH), total HIF-1α, LDHA and ACTIN protein levels from lysates of B16-F10 cells (n=4) or B16-F10 tumors [CntlKD (n=5), BNIP3KD (n=5) and ATG5KD (n=7)]). The HIF-1α-OH /HIF-1α ratio is shown in a bar graph below. Densitometric quantifications relative to ACTIN levels are shown below each corresponding band. Analysis was performed as indicated in the Data Information section, unless for HIF-1α/Actin ratio (in vivo), which was analyzed with Kruskal-Wallis non-parametric test with Dunn's multiple comparisons test, and LDHA/Actin ratio for shATG5 condition (in vitro), which was analyzed with Wilcoxon's rank test.",
    "ncbi_link": "ATG5: 11793
BNIP3: 12176"
  },
  {
    "caption": "Immunohistochemical staining for HIF-1α (brown) representative from CntlKD, BNIP3KD and ATG5KD, B16-F10 tumor tissues. Higher magnification of the highlighted (with a white square) stained sections is shown below.",
    "ncbi_link": "ATG5: 11793
BNIP3: 12176"
  },
  {
    "caption": "Immunoblot detection of Hydroxylated HIF-1α (HIF-1α-OH), total HIF-1α, LDHA, PHD2 and ACTIN protein levels from normoxic lysates of B16-F10 cells transfected in presence of non-targeting siRNA sequences (Scr) or siRNA against PHD2.",
    "ncbi_link": "PHD2: 112405"
  },
  {
    "caption": "Immunoblot detection of Hydroxylated HIF-1α (HIF-1α-OH), total HIF-1α, LDHA, NCOA4 and ACTIN levels from normoxic lysates of B16-F10 cells transfected in presence of non-targeting siRNA sequences (Scr) or siRNA against NCOA4 (n=4).",
    "ncbi_link": "NCOA4: "
  },
  {
    "caption": "Growth curves of B16-F10 tumors generated by shCntl or shBNIP3 cells expressing Luciferase (Luc) or an undegradable HIF-1α (HIF-1α-AA) construct (n=7 for CntlKD Luc/BNIP3KD HIF-1α-AA, n=8 CntlKD HIF-1α-AA and n=5 for BNIP3KD Luc) and analyzed with a two-way ANOVA with Tukey's multiple comparisons test. Representative double immunostaining for CD31 and αSMA in B16-F10 tumors (n=5 per condition). Scale bars represent 50µm.",
    "ncbi_link": "Luc: 
Luciferase: 
BNIP3: 12176
HIF-1α: 15251"
  },
  {
    "caption": "D-F. Fe contents of whole plants, FER expression in roots and relative FCR activities in the roots of plants grown under Fe-sufficient (20 µM, +Fe) or Fe-deficient (2 µM, -Fe) conditions for 7 d. Plants were exposed to high (H-, 2.0) or low (L-, 0.5) red (R) to far red (FR) ratios.",
    "ncbi_link": "FER: 543705"
  },
  {
    "caption": "C. Accumulation of HY5 protein in leaves and roots of reciprocal grafts of phyB and WT plants grown under white light (200 µmol m-2s-1) for 7 d. Rubisco and β-Actin were used as loading controls for leaves and roots in the western blot analysis, respectively. The values shown above each lane indicate the relative abundance of the HY5 protein. D. Accumulation of HY5 protein in the roots of WT and phyB plants under high (H, 2.0) or low ratio of (L, 0.5) red (R) to far red (FR) light conditions. β-Actin was used as loading controls in the western blot analysis. The values shown above each lane indicate the relative abundance of the HY5 protein. ",
    "ncbi_link": "phyB: 101264523"
  },
  {
    "caption": "D. Fe content of whole plants. WT and hy5 plants were grown under high (H) or low ratios of (L) red (R) to far red (FR) light conditions with either Fe-sufficient (20 µM, +Fe) or Fe-deficient (2 µM, -Fe) conditions for 7 d.",
    "ncbi_link": "hy5: 543733"
  },
  {
    "caption": "E. FER expression in roots. WT and hy5 plants were grown under high (H) or low ratios of (L) red (R) to far red (FR) light conditions with either Fe-sufficient (20 µM, +Fe) or Fe-deficient (2 µM, -Fe) conditions for 7 d.",
    "ncbi_link": "FER: 543705
hy5: 543733"
  },
  {
    "caption": "E. Direct binding of HY5 to the FER promoter analyzed using ChIP-qPCR in 35S-HY5-3HA-overexpressing (HY5-OE) tomato plants. WT and HY5-OE plants were exposed to white light (200 µmol m-2s-1) grown under Fe-deficient (2 µM, -Fe) conditions for 7 d. Input chromatin was isolated from root samples at 7 d. The epitope-tagged HY5-chromatin complex was immunoprecipitated with an anti-HA antibody. A control reaction was processed side-by-side using mouse IgG. Input- and ChIP-DNA samples were quantified by RT-qPCR using primers specific for the promoter and exon fragment of the FER gene as indicated in (D). The ChIP results are presented as percentage of the input DNA.",
    "ncbi_link": "3HA: 
FER: 543705
HY5: 543733"
  },
  {
    "caption": "A-C. Fe content of whole plants (A) and the photochemical efficiencies of PSI and PSII [Y(I) and Y(II)] (B and C) in young leaves of grafted tomato plants with grafts between WT/WT and WT/fer grown under H-R/FR (2.0) or L-R/FR (0.5) conditions for 7 d.",
    "ncbi_link": "fer: 543705"
  },
  {
    "caption": "D-F. Transcript levels of FER, FRO1 and IRT1 in the roots of grafted tomato plants with grafts between WT/WT and WT/fer grown under H-R/FR (2.0) or L-R/FR (0.5) conditions for 7 d.",
    "ncbi_link": "FER: 543705
fer: 543705
FRO1: 543871
IRT1: 543597"
  },
  {
    "caption": "B. The abundance of FER transcripts in the roots of WT and phyB plants grown under 20 μM Fe-EDTA in nutrient solution in a growth room.",
    "ncbi_link": "FER: 543705
phyB: 101264523"
  },
  {
    "caption": "D. Fe content in the fruits of WT and phyB plants. Plants were grown in soil in a greenhouse.",
    "ncbi_link": "phyB: 101264523"
  },
  {
    "caption": "Quantitative analysis of TSC2 mRNA (A) N = 8-10 anagen VI HFs from 4 different donors treated with siTSC2 or non-targeting oligos (NTO) for 6 days. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "Quantitative analysis of TSC2 protein expression (B). N = 8-10 anagen VI HFs from 4 different donors treated with siTSC2 or non-targeting oligos (NTO) for 6 days. (C) Representative images of TSC2 immunofluorescence. Only anagen VI HFs were investigated and analyses performed in defined reference areas (dotted areas) in the HFPU. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001. Samples from each donor are represented by a different color. Nuclei stained with DAPI.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(D) Quantitative analysis of phosphorylated S6 (p-S6) (mTORC1 activity read-out) immunoreactivity. N = 2-3 anagen VI HFs from 1 donor treated with siTSC2 or non-targeting oligos for 6 days. (E) Representative images of p-S6 immunofluorescence. : Only anagen VI HFs were investigated and analyses performed in defined reference areas (dotted areas) in the HFPU. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001. Samples from each donor are represented by a different color. Nuclei stained with DAPI.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(F) Quantitative histomorphometry of melanin production. N = 9-10 anagen VI HFs from 4 different donors treated with siTSC2 or non-targeting oligos for 6 days. (G) Representative bright field microscopic images of Masson-Fontana histochemistry. Only anagen VI HFs were investigated and analyses performed in defined reference areas (dotted areas) in the HFPU. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001. Samples from each donor are represented by a different color.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(H) Quantitative analysis of tyrosinase activity. N = 8-9 anagen VI HFs from 4 different donors treated with siTSC2 or non-targeting oligos for 6 days. (I) Representative images of tyrosinase activity immunofluorescence. : Only anagen VI HFs were investigated and analyses performed in defined reference areas (dotted areas) in the HFPU. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001. Samples from each donor are represented by a different color. Nuclei stained with DAPI.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(J) Quantitative analysis of α-MSH expression. N = 8-9 anagen VI HFs from 4 different donors treated with siTSC2 or non-targeting oligos for 6 days. (K) Representative images of α-MSH immunofluorescence. Only anagen VI HFs were investigated and analyses performed in defined reference areas (dotted areas) in the HFPU. Mean ± SEM, Unpaired Student's t-test, * p < 0.05, ** p < 0.01, **** p < 0.0001. Samples from each donor are represented by a different color. Nuclei stained with DAPI.",
    "ncbi_link": "TSC2: 7249"
  },
  {
    "caption": "(D) UV sensitivity assayed by 10-fold serial dilutions of different mutant combinations with rad3-102 allele on YPAD plates after exposure to the indicated UV-C doses. Five biological replicates have been performed.",
    "ncbi_link": "rad3: 856918"
  },
  {
    "caption": "(C) UV sensitivity assayed by 10-fold serial dilutions of different mutant combinations with rad3-102 allele on YPAD plates after exposure to the indicated UV-C doses. Four biological replicates have been performed.",
    "ncbi_link": "rad3: 856918"
  },
  {
    "caption": "(D) Synthetic combinations of rad3-102 mus81∆ with rad51∆ and pol32∆. Tetrads dissected on YPAD medium are shown. Triangles indicate either a severe growth defect or lethality.",
    "ncbi_link": "mus81: 851994
pol32: 853500
rad3: 856918
rad51: 856831"
  },
  {
    "caption": "(A) Analysis of DNA content by flow cytometry of G1 phase synchronized wild type, rad52∆, rad51∆, mus81∆ and pol32∆ cells and further released into S phase. Cells were synchronized in G1 with α -factor, treated with DMSO or 100 µM CPT, let in G1 for 1 h, and released into S phase. Three biological replicates have been performed.",
    "ncbi_link": "mus81: 851994
pol32: 853500
rad51: 856831
rad52: 854976"
  },
  {
    "caption": "(B) (C) Analysis of DNA content by flow cytometry of G1 phase synchronized wild type, rad3-102, rad3-102 rad51∆, rad3-102 mus81 and rad3-102 mus81-dd cells and further released into S phase. Cells were synchronized in G1 with α-factor, untreated or irradiated with 20 J/m2 UV-C, let in G1 for 2h, and released into S phase. Three biological replicates have been performed.",
    "ncbi_link": "mus81: 851994
rad3: 856918
rad51: 856831"
  },
  {
    "caption": "(A) Analysis of replicated DNA tracks length by single-molecule DNA combing in WT, rad52∆, rad51∆, mus81∆ and pol32∆ cells exposed to CPT. Exponentially growing cells were treated with DMSO or 50 µM CPT for 2h and then pulse-labeled with 50 µM EdU for 20min. DNA fibers were combed on silanized coverslips and EdU-labeled DNA was detected by Click chemistry. Graph depicts the distribution of EdU tracks length in kb. Box and whiskers indicate 25-75 and 10-90 percentiles, respectively. Median EdU tracks length is indicated in kb (values from two biological replicates were pooled). Asterisks indicate the P-value of the Mann-Whitney unpaired t test, **: p=0.0015. The percentage of EdU track length decrease between the DMSO and CPT conditions is indicated between parentheses for each strain. Representative images of DNA fibers are shown. Red and white: EdU, green: DNA.",
    "ncbi_link": "mus81: 851994
pol32: 853500
rad51: 856831
rad52: 854976"
  },
  {
    "caption": "(C) Analysis of replication intermediates by 2D gel electrophoresis. Replication intermediates were monitored at early origin ARS305 and region C in WT, rad3-102, mus81∆ and rad3-102 mus81∆ cells. Cells were synchronized in G1 with α-factor and collected at the indicated time points after release into S phase. A scheme of the studied chromosomal region is shown (drawn to scale). Relevant probes are indicated by gray bars, and coordinates of ARS and restriction sites are indicated in bp. Two biological replicates have been performed.",
    "ncbi_link": "mus81: 851994
rad3: 856918"
  },
  {
    "caption": "(B) (C) Kinetic analysis of Rad52 foci formation. Wild-type and mus81∆ cells containing Rad52-YFP and mCHERRY-Pus1 were synchronized in G1 with α-factor, treated with DMSO or 100 µM CPT, let in G1 for 30 min, and released into S phase. Cells were collected at the indicated time points and visualized by fluorescence microscopy. Mean ± SEM of cells with Rad52 foci are shown for each time point. Flow cytometry profiles corresponding the experimental setup are shown. Four biological replicates have been performed.",
    "ncbi_link": "mus81: 851994"
  },
  {
    "caption": "(E) CPT sensitivity assayed by 10-fold serial dilutions of S-MUS81 and G2-MUS81 alleles compared to the wild type, mus81, mms4∆ and cdc5-2 mutants. Three biological replicates have been performed.",
    "ncbi_link": "cdc5: 855013
mms4: 852395
mus81: 851994
MUS81: 851994"
  },
  {
    "caption": "(F) UV sensitivity assayed by 10-fold serial dilutions of S-MUS81 and G2-MUS81 alleles in combination with rad3-102 on YPAD plates after exposure to the indicated UV-C doses. Three biological replicates have been performed.",
    "ncbi_link": "MUS81: 851994
rad3: 856918"
  },
  {
    "caption": "(A) (B) Pulsed-field gel electrophoresis (PFGE) analysis of wild type, mus81∆, cdc5-2 and G2-MUS81 cells in response to CPT. Cells were synchronized in G1 with α-factor, treated with DMSO or 100 µM CPT, let in G1 for 1 h, and released into S phase. Cells were collected at the indicated time points. DNA contents was analyzed by flow cytometry and the DNA extracted in agarose plugs was analyzed by PFGE. Upper panel: agarose gel stained with ethidium bromide; lower panel: Southern blot using a chromosome IV specific probe. JMs, joint molecules accumulated in the gel wells. The mean value of JMs relative to the total amount of DNA is indicated for each time point. Two to three biological replicates have been performed.",
    "ncbi_link": "cdc5: 855013
mus81: 851994
MUS81: 851994"
  },
  {
    "caption": "(C) (D) PFGE analysis of rad52∆ and rad52∆ mus81∆ cells in response to CPT performed as in (A) (B). The gel has been stained with Ethidium bromide and densitometry profiles corresponding to the +CPT 140 min time points in rad52∆ and rad52∆ mus81∆ cells are shown. Two biological replicates have been performed.",
    "ncbi_link": "mus81: 851994
rad52: 854976"
  },
  {
    "caption": "Tau levels in the cortex (A, C-E) and hippocampus (B, F-H) of 4-10-month-old mice were determined by western blot analysis. (A, B) Representative western blots of cortical (A) and hippocampal (B) homogenates from mice of the indicated genotypes show levels of hTau (HT7) and total tau (Tau5). Actin served as a loading control. (C-H) Quantitation of western blot signals for full-length tau detected with the mTau/hTau cross-reactive antibodies Tau5 (C, F) or EP2456Y (D, G) or the hTau-specific antibody Tau12 (E, H). n = 3-8 mice per group. *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed unpaired t test (E, H) or by Welch's one-way ANOVA with post-hoc two-tailed Welch's t test (C, D, F, G). P values were Holm-adjusted for multiple comparisons. Values are means ± SEM.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "Tau expression in the cortex (A, C, E) and hippocampus (B, D, F) of 4-10-month-old mice was determined by quantitative RT-PCR (A, B). (A, B) hTau mRNA levels in tissue homogenates were determined by quantitative RT-PCR.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "Tau expression in the cortex (A, C, E) and hippocampus (B, D, F) of 4-10-month-old mice was determined by western blot analysis (C-F).(C, D) Western blots from Figure 1A and B were enhanced to better reveal tau fragments of ~40 kDa. (E, F) Quantitation of western blot signals for tau fragments of ~40 kDa detected with Tau5 in tissue homogenates. n = 3-4 mice per group. *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed unpaired t test (A, B) or by Welch's one-way ANOVA with post-hoc two-tailed Welch's t test (E, F). P values were Holm-adjusted. Values are means ± SEM.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "Coronal brain sections from 2-4-month-old mice of the indicated genotypes were immunostained with different tau antibodies. (A-I) Sections of hemibrain (A-C), whole hippocampus (D-F), and CA1 region (G-I) immunostained for hTau (HT7). (J-O) Hippocampal sections immunostained with phosphorylation-dependent tau antibodies: PHF1 (p396, 404) (J-L), AT8 (pSer 199, 202, and pThr 205) (M-O).",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "Six-month-old hTau-A152T(L1) mice and NTG controls were or were not treated with DOX for 2 months and analyzed at 8 months of age by immunohistochemistry. (A-I) Untreated hTau-A152T(L1) mice had increased neuronal labeling with the hTau antibody HT7 (A), the phosphorylation-dependent tau antibody PHF1 (D), and the conformation-dependent tau antibody MC1 (G). HT7 (A) and PHF1 (D) staining patterns were similar. MC1 (G) specifically stained hippocampal mossy fibers. In hTau-A152T(L1) mice, DOX reduced hippocampal staining with HT7, PHF1, and MC1 (B, E, H) to the levels in DOX-treated NTG controls (C, F, I).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "(J-M) DOX also normalized CA1 levels of GFAP immunoreactivity (IR) in hTau-A152T(L1) mice, as shown by representative photomicrographs (J-L) and quantitation of GFAP immunoreactivity (M). Scale bars: 300 µm (A-I), 25 µm (J-L). n = 3-4 mice per genotype. *P < 0.05 by two-tailed Welch's t test without Holm adjustment. Values are means ± SEM. a.u., arbitrary units.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "Nesting behavior of mice at 10-14 months of age was scored 0-7 by an investigator blinded to genotype. n = 17 NTG, 12 CaMKII-tTA, 13 hTau-WT(L32), and 10 hTau-A152T(L1). Nest building was significantly impaired only in hTau-A152T(L1) mice (P < 0.01 at 2 and 6 h) and CaMKII-tTA mice (P < 0.05 at 2 h, P < 0.01 at 6 hours) by nonparametric Wilcoxon rank-sum test with gatekeeping approach and Holm adjustment. Values are means ± SEM.",
    "ncbi_link": "CaMKII: 12322
Tau: 4137"
  },
  {
    "caption": "Mice from cohorts 1-3 were tested in the MWM at the indicated ages. (A-D, M, N) Learning curves of mice in cohorts 1 (A-D) and 3 (M, N). Data at day 0 are from the first trial on day 1. Data from cohort 2 are shown in EV5B-G. Compared with NTG controls, only hTau-A152T(L1) mice showed significant learning impairments at 4-6, 17-19 (cohort 1, P < 0.001) and 17-21 (cohort 3, P < 0.01) months of age by Cox proportional hazards model analysis with mixed effects and Holm adjustment for the following comparisons for each age range: NTG versus CaMKII-tTA, NTG versus TRE-hTau-A152T(L1), and NTG versus hTau-A152T(L1) for cohort 1, and NTG versus CaMKII-tTA, NTG versus hTau-WT(L32), NTG versus hTau-A152T(L1), and hTau-WT(L32) versus hTau-A152T(L1) for cohort 3. (E-L, O-V) Performance of mice from cohorts 1 (E-L), 3 (O-R) and 1-3 combined (S-V) in a probe trial (platform removed) 24 h after the last training trial. (E-H, O, P, S, T) Latency to reach original platform location. (I-L, Q, R, U, V) Number of times mice crossed the original platform location (black bars) or the average of their crossings of corresponding locations in the three other quadrants (white bars). Cohort 1: n = 12 (A-L) NTG; 13 (A, B, E, F, I, J), 11 (C, G, K), or 9 (D, H, L) TRE-hTau-A152T(L1); 11 (A, B, E, F, I, J), 10 (C, G, K), or 9 (D, H, L) CaMKII-tTA; and 14 (A, B, E, F, I, J), 13 (C, G, K), or 12 (D, H, L) hTau-A152T(L1) mice. Cohort 3: n = 17 (M-R) NTG; 12 (M, O, Q) or 11 (N, P, R) CaMKII-tTA; 13 (M, O, Q) or 12 (N, P, R) hTau-WT(L32); and 10 (M-R) hTau-A152T(L1) mice. Cohorts 1+2+3: n = 47 (S, U), or 39 (T, V) NTG; 11 (S, U) or 9 (T, V) TRE-hTau-A152T(L1); 34 (S, U) or 31 (T, V) CaMKII-tTA; 13 (S, U) or 12 (T, V) hTau-WT(L32); and 43 (S, U) or 36 (T, V) hTau-A152T(L1) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by Cox proportional hazards/mixed effects model analysis (A-D, M, N), one-way ANOVA with post-hoc Tukey (E-H, O, P) or Dunnett's (S, T) test, or one-tailed paired t test with Holm adjustment (I-L, Q, R, U, V). Values are means ± SEM.",
    "ncbi_link": "CaMKII: 12322
Tau: 4137"
  },
  {
    "caption": "(A-C) One cohort of mice was assessed with the social approach test at young (A) and old (B) age and another cohort of mice at middle age (C). Mice were placed individually into the empty center chamber of a three-chamber apparatus. One side-chamber contained an empty cup, and the other an identical cup with an unfamiliar live mouse in it. Close contact with each cup was monitored for 10 min. n = 12 (A, B) or 17 (C) NTG; 13 (A) or 10 (B) TRE-hTau-A152T(L1); 12 (A), 9 (B), or 12 (C) CamKII-tTA; 13 (C) hTau-WT(L32); and 14 (A), 12 (B), or 10 (C) hTau-A152T(L1) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by one-tailed paired t test with Holm adjustment. Values are means ± SEM.",
    "ncbi_link": "CamKII: 12322
Tau: 4137"
  },
  {
    "caption": "(A-F) Coronal brain sections obtained from mice at 4-6 (A-C) or 20-23 (D-F) months of age were immunostained for NeuN. The number of NeuN-positive cells with neuronal morphology was determined in dentate gyrus (A, D), CA3 (B, E), and CA1 (C, F). n = 11 (A-C) or 18 (D-F) NTG; 11 (A-C) or 5 (D-F) CamKII-tTA; 7 (A-C) or 9 (D-F) hTau-WT(L32); and 14 (A-C) or 10 (D-F) hTau-A152T(L1) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by one-way ANOVA and Tukey test. Values are means ± SEM.",
    "ncbi_link": "CamKII: 12322
Tau: 4137"
  },
  {
    "caption": "(F) Mossy fiber LTP at 20 months of age. n (mice/slices) = 5-9/8-21 (NTG), 2-5/5-12 (CaMKII-tTA), 3-6/8-14 (TRE-hTau), 3-6/8-14 (hTau-WT), and 5-6/8-14 (hTau-A152T). *P < 0.05, **P < 0.01, ***P < 0.001 versus NTG by linear regression analysis with Holm adjustment (B, C) or by one-way ANOVA and Dunnett's test (D, E). No significant difference was detected by two-way ANOVA in (F). Values are means ± SEM.",
    "ncbi_link": "CaMKII: 12322
Tau: 4137"
  },
  {
    "caption": "(A-C) Subdural EEG recordings from freely behaving mice at 4-9 months of age before (A top trace, B) and after (A bottom trace, C) injection of PTZ at a dose (30 mg/kg) that did not produce convulsions. (A) Representative EEG traces from an hTau-A152T(L1) mouse. Arrows indicate epileptic discharges. (B, C) Quantitation of spikes per hour at baseline (B) and of spikes per 20-min intervals after PTZ injection (C). n = 31 (B) or 23 (C) NTG; 13 (B) or 11 (C) CaMKII-tTA; 12 (B) or 10 (C) hTau-WT(L32); and 22 (B) or 21 (C) hTau-A152T(L1) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by Welch's one-way ANOVA and two-tailed Welch's t test with Holm adjustment (B) or by two-way repeated-measures ANOVA and Tukey test (C). Values are means ± SEM.",
    "ncbi_link": "CaMKII: 12322
Tau: 4137"
  },
  {
    "caption": "(A-D) Numbers of offspring from crosses of hAPP-J20 mice with hTau-A152T(L1) (A, B) or hTau-WT(L32) (C, D) mice that were (A, C) or were not (B, D) treated with DOX. (E) Numbers of offspring from crosses of lower expresser hAPP-J9 mice with hTau-A152T(L1) mice that were not treated with DOX. n = 141 (A), 112 (B), 94 (C), 83 (D), and 282 (E) mice per cohort. Yields from two crosses indicated significant deviations from Mendelian inheritance: hAPP-J20 x TRE-hTau-A152T(L1) x CaMKII-tTA without DOX (Holm-adjusted P = 0.003, unadjusted P = 0.0008) and hAPP-J9 x TRE-hTau-WT(L32) x CaMKII-tTA without DOX (adjusted and unadjusted P < 0.0001) by chi-square goodness-of-fit test.",
    "ncbi_link": "APP: 351
CaMKII: 12322
Tau: 4137"
  },
  {
    "caption": "(F) Subdural EEG recordings from untreated 3-10-month-old mice were analyzed to compare their number of spikes at baseline. n = 8 NTG, 6 hAPP-J9, 6 hTau-A152T(L1), and 8 hAPP-J9/hTau-A152T(L1). *P < 0.05, **P < 0.01 by logistic regression analysis for three-way interaction of the three transgenes with Holm adjustment (A-E) or by two-tailed Welch's t test with Holm adjustment (F).",
    "ncbi_link": "APP: 351
Tau: 4137"
  },
  {
    "caption": "B. Images of rosettes and seedlings (15 DAG) of Col-0, arf7/arf19, slr, and gLBD16-SRDX as well as the inducible lateral-root-less lines pGATA23::shy2-2-GR and pGATA23::slr1-GR grown on DMSO control medium or 30 µM Dexamethasone (DEX), Scale bar 1 cm. The rosettes were stained with a Lugol's Iodine solution for starch accumulation at the end of the dark period (representative images of n=3 biological replicates). C. Box plots of starch quantification in rosette tissues at 15 DAG (n=4 biological replicates). Comparison between samples was performed by one-way ANOVA and post-hoc Tukey HSD Test (α = 0.05); different letters indicate significant differences.",
    "ncbi_link": "arf19: 838505
slr1: 3767379
GATA23: 832751
slr: 827102
LBD16: 818843
arf7: 832196
shy2: 839570"
  },
  {
    "caption": "E. Representative confocal sections of calcofluor counterstained (E, n=5 biological replicates) and differential interference contrast (DIC) images of GUS-stained root bends (F, n=16 biological replicates) in DR5:GUS seedlings treated as indicated 48h after gravistimulation. In E, orange arrows indicate the pericycle (marked in yellow). F. Fraction of root bends forming an LRP and showing DR5 GUS staining after treatment with either control or 2D containing agar blocks (n=16 biological replicates, ± SE).",
    "ncbi_link": "GUS: "
  },
  {
    "caption": "A. Representative western blot of root tissues of pUB10:S6K1-3xHA treated by the indicated combination of auxin (IAA, 10µM), sucrose (Suc, 110mM), 2-deoxy-d-glucose (2D, 20mM) and AZD8055 (AZD, 10µM) and probed with anti-S6K1/2, anti-HA or anti-S6K1-T449P. Blot is one of three biological replicates. B. Quantification of the relative S6K activation. Box plots show three biological replicates, and comparison between samples was performed by one-way ANOVA and post-hoc Tukey HSD Test (α = 0.05); different letters indicate significant differences.",
    "ncbi_link": "HA: 
UB10: 843442
S6K1: 820020"
  },
  {
    "caption": "C. Representative DIC images showing RPT1B promoter expression at different stages of LR development in 10 DAG seedlings. Orange arrowheads indicate the accumulation of reporter signals in the dividing lateral root founder cells. Scale bars: 50 µm. D. Representative confocal section showing S6K1 expression in different stages of LR development in 10 DAG pS6K1:gS6K1-CFP seedlings. Orange arrowheads indicate the accumulation of reporter signals in the dividing lateral root founder cells. Scale bars: 50 µm.",
    "ncbi_link": "CFP: 
S6K1: 820020"
  },
  {
    "caption": "A-C. Box plots of emerged LR in TOR-oe (A), rpt1b (B), and lst8 (C) at 14 DAG. Comparison between samples was performed by one-way ANOVA and post-hoc Tukey HSD Test (α = 0.05); different letters indicate significant differences. The number of roots scored is indicated.",
    "ncbi_link": "lst8: 816739///821339
rpt1b: 820032
TOR: 841427"
  },
  {
    "caption": "H. Fraction of bends developing lateral root primordia and stained for GUS activity in primary root vasculature of UB10pro>>amiR-TOR/DR5:GUS, n=18 bends.",
    "ncbi_link": "GUS: 
UB10: 843442
TOR: 841427"
  },
  {
    "caption": "E, F. Abundance of ARF19 (E) and LBD16 (F) transcripts in RNAseq samples. mRNA accumulation in response to auxin is comparable for both, whether TOR is knocked down. n=3 biological replicates.",
    "ncbi_link": "ARF19: 838505
LBD16: 818843
TOR: 841427"
  },
  {
    "caption": "G, H. Relative expression levels (normalized to ACTIN) of ARF19 (G) and LBD16 (H) measured by RT-qPCR upon TOR activity inhibition with AZD8055. Comparison between samples was performed by one-way ANOVA. Different letters indicate significant differences based on a post-hoc Tukey HSD Test (n=5 biological replicates, α = 0.05).",
    "ncbi_link": "ACTIN: 821411
ARF19: 838505
LBD16: 818843"
  },
  {
    "caption": "L, M. Total lysates prepared from lateral roots treated or not with IAA and AZD were fractionated through sucrose gradients, and the relative redistribution (percentage of total) of ACTIN, ARF7, ARF19, and LARP1 mRNAs in every 8 fractions were studied by RT-qPCR analysis. (L) Polysome profiles. 40S, small ribosomal subunit; 60S, large ribosomal subunit; 80S, mono-ribosome; polysomes, polyribosomes. AU is arbitrary units of RNA absorbance at A260 nanometers. (M) RT-qPCR analysis of mRNA redistribution through a sucrose gradient (8 fractions collected). Translation efficiency was computed as a percentage of mRNA in non-polysome fractions (40/60/80S; fractions 1-3) against both lights (fractions 4-5) and heavy polysomes (fractions 6-8). The plot is representative of three independently performed experiments with similar results.",
    "ncbi_link": "ACTIN: 821411
ARF19: 838505
LARP1: 128944539
ARF7: 832196"
  },
  {
    "caption": "A. Abundance of WOX11 transcripts in RNAseq samples. mRNA accumulation in response to auxin is elevated when TOR is knocked down. n=3 biological replicates.",
    "ncbi_link": "TOR: 841427
WOX11: 821196"
  },
  {
    "caption": "B. Distribution of GUS-staining in UB10pro>>amiR-TOR/WOX11pro::GUS seedlings 6 days after transfer to 10µM Est. The proportion of root bends with the depicted phenotype is indicated.",
    "ncbi_link": "GUS: 
UB10: 843442
TOR: 841427
WOX11: 821196"
  },
  {
    "caption": "C. The arf7/arf19 mutant shows defective LR initiation. D. Formation of roots (arrows) close to the wound site of arf7/arf19 primary roots 6 days after excision (DAE). E. Blocking TOR-activity via exposure to 10µM AZD8055 (AZD) resulted in the loss of rooting capability on the wound site of arf7/arf19 primary roots at 6 DAE. S",
    "ncbi_link": "arf19: 838505
arf7: 832196"
  },
  {
    "caption": "F, G. Close-ups indicate root formation location or absence of root formation on ctrl media and AZD-containing media, respectively, in arf7/arf19 primary roots at 6 DAE. The proportion of root wound sites with the depicted phenotype is indicated.",
    "ncbi_link": "arf19: 838505
arf7: 832196"
  },
  {
    "caption": "Relative expression levels of PUAR under WL, SH, and dark (DK) conditions determined by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 1 h. The seedlings were grown under DK for 4 d or transferred to WL for 6 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by t-test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: "
  },
  {
    "caption": "Relative expression levels of PUAR in Col-0, phyB-9, phyA-211, and pif7-1 by RT-qPCR under Red (R = 100 µE), Far-red (FR = 10 µE), or SH conditions. For R and FR conditions, the seedlings were grown under R or FR for 4 d. For SH conditions, the seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 1 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by t-test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
phyA: 837483
phyB: 816394
pif7: 836248"
  },
  {
    "caption": "Hypocotyl phenotypes of Col-0, PUARox, PUAR-S1ox, The seedlings were grown under white light for 4 d, and then maintained under white light or transferred to shade for 3 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). The scale bar represents 2 mm. Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates).",
    "ncbi_link": "PUAR: "
  },
  {
    "caption": "Relative hypocotyl lengths under FR compared with those of seedlings grown under DK conditions. The scale bar represents 2 mm. P-values indicate statistically significant differences (*P-value < 0.05) by t-test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates). J. Hypocotyl phenotypes of Col-0, PHYAox, and amiR-puar. The seedlings were grown under white light for 3 d, and then maintained under white light or transferred to shade for 4 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). The scale bar represents 2 mm. Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates).",
    "ncbi_link": "puar: 
PHYA: 837483"
  },
  {
    "caption": "Relative expression levels of PHYA in Col-0, pif7-1, PUARox, PUAR-S1ox, by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. The left Y-axis is relative expression level of PUAR, and the right Y-axis is the ratio of relative expression level under shade conditions to that under white light conditions. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
PHYA: 837483
pif7: 836248"
  },
  {
    "caption": "PHYA protein levels in Col-0, pif7-1, PUARox, PUAR-S1ox, by western-blot. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Tubulin indicates the loading control.",
    "ncbi_link": "PUAR: 
pif7: 836248"
  },
  {
    "caption": "Relative expression levels of PHYA in Col-0 TATA-mut, and amiR-puar by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. The left Y-axis is relative expression level of PUAR, and the right Y-axis is the ratio of relative expression level under shade conditions to that under white light conditions. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
puar: 
PHYA: 837483"
  },
  {
    "caption": "PHYA protein levels in Col-0, TATA-mut, and amiR-puar by western-blot. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Tubulin indicates the loading control.",
    "ncbi_link": "puar: "
  },
  {
    "caption": "G-H. Hypocotyl phenotypes of Col-0, phyA-211, PUARox, PUAR-S1ox, PUARox/phyA-211, GFPox, PHYAox, PUAR-S1ox, and PHYAox*PUAR-S1ox. The seedlings were grown under white light for 4 d, and then maintained under white light or transferred to shade for 3 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates).",
    "ncbi_link": "GFP: 
PUAR: 
phyA: 837483
PHYA: 837483"
  },
  {
    "caption": "Detection of PUAR in the nuclear and non-nuclear fractions by RT-qPCR. U6 and tRNA were used as RNA markers for the nuclear and non-nuclear fractions, respectively. The seedlings were grown under white light for 6 d, and then maintained under white light, or transferred to shade for 4 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 4, n refers to technical replicates).",
    "ncbi_link": "PUAR: 
U6: 835191"
  },
  {
    "caption": "Remaining levels of PHYA and GAPDH at different time points post 1 mM cordycepin in Col-0 and PUAR-S1ox lines. 6 d-old seedlings were shade-treated for 4 h prior to cordycepin treatment. SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Data are presented as means ± SD (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
GAPDH: 819567
PHYA: 837483"
  },
  {
    "caption": "Interaction between PUAR and PIF7 was determined using an in vivo pull-down assay. RNA-protein extracts were from plants that overexpressed PIF7-Flash*Col-0 and PIF7-Flash*PUAR-S1ox, respectively. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Streptavidin-coupled agarose beads were added in the reaction mix to isolate RNA complex for 2 h.",
    "ncbi_link": "PUAR: 
Flash: 
PIF7: 836248"
  },
  {
    "caption": "Relative expression levels of PHYA in Col-0, pif7-1, and PIF7-Flash by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 1 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).   Relative expression levels of PHYA in Col-0, phyB-9, and pif7-1*phyB-9 by RT-qPCR. The seedlings were grown under white light for 6 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).  ",
    "ncbi_link": "Flash: 
PHYA: 837483
phyB: 816394
pif7: 836248
PIF7: 836248"
  },
  {
    "caption": "PIF7 specifically binds to 5′ UTR of the PHYA in vitro. Purified His-PIF7 from E. coli was incubated with the biotinylated 5′ UTR of the PHYA fragment at 4 °C for 1 h, and then non-biotinylated 5′ UTR of the PHYA fragment was added according to the dose, as shown in the figure, at 4 °C for 1 h. These reaction systems were further incubated with streptavidin-coupled agarose beads in the reaction mix to isolate DNA complex for at 4 °C for 1 h.",
    "ncbi_link": "PHYA: 
PIF7: "
  },
  {
    "caption": "Hypocotyl phenotypes of Col-0, pif7-1, phyA-211, and pif7-1*phyA-211 under WL and SH. The seedlings were grown under white light for 4 d, and then maintained under white light or transferred to shade for 3 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). The scale bar represents 2 mm. Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates).",
    "ncbi_link": "phyA: 837483
pif7: 836248"
  },
  {
    "caption": "Hypocotyl phenotypes of Col-0, pif7-1, PUARox, and PUARox/pif7-1. The seedlings were grown under white light for 4 d, and then maintained under white light or transferred to shade for 3 d. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). The scale bar represents 2 mm. Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n ≥ 16, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
pif7: 836248"
  },
  {
    "caption": "Relative expression levels of PHYA in Col-0, pif7-1, PUARox, and PUARox/pif7-1 by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 4 h. WL, white light (R = 20 µE, B = 20 µE, FR = 5 µE). SH, shade (R = 10 µE, B = 5 µE, FR = 60 µE). Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "PUAR: 
PHYA: 837483
pif7: 836248"
  },
  {
    "caption": "PUAR specifically blocks the binding of PIF7 to the 5′ UTR of PHYA in vitro. Purified TF-His-PIF7 from E. coli was incubated with the biotinylated 5′ UTR of the PHYA fragment or fragment of the PIL1 promoter at 4 °C for 1 h, and then PUAR or anti-PUAR was added according to the dose as shown in the figure, at 4 °C for 1 h. These reaction systems were further incubated with streptavidin-coupled agarose beads in the reaction mix to isolate DNA complex for at 4 °C for 1 h.",
    "ncbi_link": "PHYA: 
PIL1: 819311"
  },
  {
    "caption": "I-J. Relative expression levels of PHYA and PIL1 in Col-0, PIF7-Flash, PUAR-S1ox, PIF7-Flash*Col-0, and PIF7-Flash*PUAR-S1ox by RT-qPCR. The seedlings were grown under white light for 6 d, and then maintained under white light or transferred to shade for 1 h. Different letters indicate statistically significant differences (P-value < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "Flash: 
PUAR: 
PHYA: 837483
PIF7: 836248
PIL1: 819311"
  },
  {
    "caption": "B Quantitative RT-PCR detection of microRNA-34a/b/c-5p family members in the lung over the course of normal (21% O2) and aberrant (85% O2) alveolarization. C Quantitative RT-PCR detection of microRNA-34a/b/c-3p family members in the lung over the course of normal (21% O2) and aberrant (85% O2) alveolarization.",
    "ncbi_link": "microRNA-34a: 723848"
  },
  {
    "caption": "A Qualitative analysis of lung structure in Richardson-stained plastic-embedded lung sections from wild-type (WT) and miR-34a-/- mice during normal and aberrant alveolarization (scale bar, 50 µm). B Quantification of total number of alveoli by design-based stereology in wild-type (WT) and miR‑34a-/- mice (34a-/-) during normal and aberrant alveolarization. C Quantification of mean septal thickness by design-based stereology in wild-type (WT) and miR‑34a-/- mice (34a-/-) during normal and aberrant alveolarization. ",
    "ncbi_link": "34a: 723848
miR-34a: 723848
miR‑34a: 723848"
  },
  {
    "caption": "D Qualitative analysis of lung structure in Richardson-stained plastic-embedded lung sections from wild-type (WT) and miR-34bc-/- mice during normal and aberrant alveolarization (scale bar, 50 µm). E Quantification of total number of alveoli by design-based stereology in wild-type (WT) and miR‑34bc-/- mice (34bc-/-) during normal and aberrant alveolarization. F Quantification of mean septal thickness by design-based stereology in wild-type (WT) and miR‑34bc-/- mice (34bc-/-) during normal and aberrant alveolarization. ",
    "ncbi_link": "miR-34b: 723849
miR‑34b: 723849"
  },
  {
    "caption": "G Localization of miR-34a expression by β-galactosidase activity staining in the developing lungs of P14 miR-34a::lacZ+/+ mice that were undergoing normal or aberrant alveolarization (scale bar, 50 µm; larger and some additional images are presented in Appendix Fig S2).",
    "ncbi_link": "lacZ: 
miR-34a: 723848"
  },
  {
    "caption": "B Immunoblot detection of PDGFRα levels in MLg cells after treatment with scrambled microRNA (SCR) or a miR-34a (MIM34a) mimic (n = 3 separate cell cultures for each group).",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "C Quantitative RT-PCR detection of miR-34a/b/c-5p levels in MLg cells in vitro, maintained under 21% O2 or 85% O2 (n = 3 separate cell cultures for each group).",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "E Immunoblot detection of PDGFRα levels in MLg cells in vitro, maintained under 21% O2 or 85% O2, where cells had been transfected wither with a scrambled (SCR) antimiR, or an antimiR directed against miR-34a (A34a) (n = 3 separate cell cultures for each group).",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "F Quantitative RT-PCR detection of miR-34a-5p levels in PDGFRα+ cells, sorted by FACS from the lungs of mouse pups (n = 4 animals for each group; data from an independent repetition are provided in Appendix Fig S5) at P5, maintained under 21% O2 or 85% O2 from birth.",
    "ncbi_link": "miR-34a-5p: 723848"
  },
  {
    "caption": "H Quantitative RT-PCR detection of miR-34a-5p levels in PDGFRα+ cells, sorted by FACS from the lungs of either wild-type (34awt/wt) mouse pups, or mouse pups in which miR-34a expression in Pdgfra‑expressing cells (34ai∆PC/i∆PC) at P5 (n = 4 animals for each group).",
    "ncbi_link": "34a: 723848
miR-34a: 723848
miR-34a-5p: 723848"
  },
  {
    "caption": "I Qualitative analysis of lung structure in Richardson-stained plastic-embedded lung sections from 34awt/wt or 34ai∆PC/i∆PC mouse pups at P14 during aberrant (85% O2) alveolarization, compared with 34ai∆PC/i∆PC during normal (21% O2) alveolarization (scale bar, 50 µm). Data are representative of observations made in four other experiments. J Quantification of total number of alveoli by design-based stereology in 34awt/wt or 34ai∆PC/i∆PC mouse pups at P14, during normal and aberrant alveolarization (n = 5 animals for each group). K Quantification of mean septal thickness by design-based stereology in 34awt/wt or 34ai∆PC/i∆PC mouse pups at P14, during normal and aberrant alveolarization (n = 5 animals for each group). ",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "B Evaluation of the specificity of TSB1 and TSB2 in MLg cells using scrambled miR (SCR) and miR-34a (MIM34a) mimics, and probing for PDGFRα and c-Kit as TSB‑dependent and TSB‑independent target readouts, respectively. Protein loading equivalence was controlled by βactin levels. Note: PDGFRα, βactin, and c-Kit were all probed on the same membrane; hence a single βactin immunoblot is presented. Data are representative of three experiments.",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "C Evaluation of the specificity of TSB1 and TSB2 in MLg cells using scrambled miR (SCR) and miR-34a (MIM34a) mimics, and probing for PDGFRα and SIRT1 as TSB‑dependent and TSB‑independent target readouts, respectively. Protein loading equivalence was controlled by βactin levels. Note: PDGFRα, βactin, and SIRT1 were all probed on the same membrane; hence a single βactin immunoblot is presented. Data are representative of three experiments.",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "B Quantitative RT-PCR detection of miR-34a-5p levels in wild-type mouse pups at post-natal day (P)14 that had been treated either with a scrambled antimiR (S), or antimiR-34a (A34a), during normal (21% O2) and aberrant (85% O2) alveolarization (n = 4 animals for each group).",
    "ncbi_link": "34a: 723848
miR-34a-5p: 723848"
  },
  {
    "caption": "C Qualitative analysis of lung structure in Richardson-stained plastic-embedded lung sections from wild-type mouse pups at post-natal day (P)14, treated with either scrambled antimiR (S), or antimiR-34a (A34a), during normal and aberrant alveolarization (scale bar, 50 µm). Data are representative of three or more experiments.",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "D Quantification of total number of alveoli by design-based stereology in wild-type mouse pups at post-natal day (P)14, treated with either scrambled antimiR (S), or antimiR-34a (A34a), during normal and aberrant lung alveolarization (n = 5 animals for each group).",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "E Quantification of mean septal thickness by design-based stereology in in wild-type mouse pups at post-natal day (P)14, treated with either scrambled antimiR (S), or antimiR-34a (A34a), during normal and aberrant alveolarization (n = 5 animals for each group).",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "F Quantitative analysis of PDGFRα+ cells by flow cytometry, in lungs from wild-type mouse pups at P5, treated with either scrambled antimiR (S), or antimiR-34a (A34a), during normal and aberrant alveolarization (n = 5 animals for each group).",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "G Quantitative analysis of PDGFRα+/αSMA+ cells by flow cytometry, in lungs from wild-type mouse pups at P5, treated with either scrambled antimiR (S), or antimiR-34a (A34a), during normal and aberrant alveolarization (n = 5 animals for each group).",
    "ncbi_link": "34a: 723848"
  },
  {
    "caption": "A Mice expressing nuclear‑localized GFP under the control of the Pdgfra promoter were maintained under normoxic (21% O2) or hyperoxic (85% O2) conditions, and lungs were harvested, processed and immunostained for Ki67 to determine proliferation status. DAPI staining revealed nuclei of all cells present in the section. Low-magnification images from individual channels are presented to the right of the merged (large) image first row of images. The area demarcated by the white box in the merge image of the first row is magnified in the second and third rows to allow for visualization of greater magnification of the demarcated region of the merged image, as well as visualization of a single Ki67+,GFP+ cell (white arrowhead) in all three channels separately.",
    "ncbi_link": "Pdgfra: 18595"
  },
  {
    "caption": "The impact of administration of scrambled antimiR (S) or an antimiR directed against miR-34a (A34a) on the abundance of type I alveolar epithelial cells (marked by aquaporin 5, Aqp5) and type II alveolar epithelial cells (marked by pro-surfactant protein C, Sftpc) was assessed in 3-µm sections of paraffin‑embedded lung tissue from P5 mice undergoing normal (21% O2) or aberrant (85% O2) lung alveolarization. DAPI, 4′,6-diamidino-2-phenylindole. In the DAPI images, white lines delineate tissue from airspaces, and in the 85% O2 groups demarcate septa. Antibody specificity was validated by rabbit IgG isotype control primary antibodies. The control experiments for the Aqp5 and Sftpc staining runs are illustrated here. Scale bars, 50 µm.",
    "ncbi_link": "miR-34a: 723848"
  },
  {
    "caption": "B Quantification of the expression of miR-19a and miR-19b in bones of mice treated with PTH (n=15) or Scl-Ab (n=14) compared to veh (n=13) control. C Quantification of the expression of miR-19a and miR-19b in calvarial osteoblasts upon in vitro stimulation with PTH or Wnt3a compared to veh control (n=3).",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527"
  },
  {
    "caption": "D Alkaline phosphatase staining of differentiating calvarial osteoblasts transfected with a scrambled (scr) control miRNA, anti-sense microRNA (anti-miR) inhibiting miR-19a or miR-19b or a combination thereof (anti-miR-19a/b) (representative image of 4 independent experiments). E Quantification of alkaline phosphatase staining of calvarial osteoblasts transfected with scr, anti-miR-19a, anti-miR-19b or anti-miR-19a/b (n=4).",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527"
  },
  {
    "caption": "F, G Expression analysis of osteoblast marker genes (F) Runx2 and (G) Type I Collagen (Col1a1) in calvarial osteoblasts transfected with scr, anti-miR-19a, anti-miR-19b or anti-miR-19a/b (n=4).",
    "ncbi_link": "Col1a1: 12842
Type I Collagen: 12842
miR-19a: 723891
miR-19b: 751527
Runx2: 12393"
  },
  {
    "caption": "H Images of von Kossa-stained histological sections of the proximal tibiae of 12-week-old male C57Bl/6J mice and fluorescence double labeling to visualize bone formation (insets) after 4-weeks of treatment with anti-miR-19a/b (n=12), scr control oligonucleotides (n=11) or veh (n=8). Scale bars indicate 1 mm (black) and 50 μm (white). I Bone histomorphometric analysis of the proximal tibiae of the same animals as in (H) Abbreviations: BV/TV, bone volume/tissue volume; MS/BS, mineralizing surface/bone surface; BFR/BS, bone formation rate/bone surface; MAR, mineral apposition rate; OS/BS, osteoid surface/bone surface; Ob.S/BS, osteoblast surface/bone surface; N.Ob/BS, number of osteoblasts/bone surface; ES/BS, eroded surface/bone surface; Oc.S/BS, osteoclast surface/bone surface; N.Oc/BS, number of osteoclasts/bone surface.",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "J Images of von Kossa-stained histological sections of the fourth lumbar vertebral body of 12-week-old mice after 4-weeks of treatment with anti-miR-19a/b, scr or veh. Scale bar indicates 1 mm. K Quantification of bone mass (BV/TV) of the fourth lumbar vertebral body of 12-week-old mice after 4-weeks of treatment with anti-miR-19a/b (n=12), scr (n=12) or veh (n=8).",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "A Images of von Kossa-stained histological sections of the bone and bone marrow (upper panel) and of hematoxylin-eosin-stained liver sections (lower panel) of 12-week-old mice after treatment with anti-miR-19a/b (n=12), scrambled (scr) control oligonucleotides (n=11) or vehicle (veh) (n=8). Scale bars indicate 100 μm (upper panel) and 50 μm (lower panel). B, C Quantification of the femur length (B) and width (C) after treatment with anti-miR-19a/b (n=8), scr (n=7) or veh (n=8).",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "D, E Quantification of the expression of miR-19a (D) and miR-19b (E) in the bone, bone marrow and liver after treatment with anti-miR-19a/b (n=4), scr (n=4) or veh (n=3).",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527"
  },
  {
    "caption": "F-H Quantification of the expression of the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (Gapdh), beta-2 microglobulin (b2m), beta-actin 1 (β-actin 1) and beta-actin 2 (β-actin 2) in the bone (F), bone marrow (G) and liver (H) after treatment with anti-miR-19a/b (n=4), scr (n=4) or veh (n=3).",
    "ncbi_link": "beta-actin 1: 11461
β-actin 1: 11461
beta-actin 2: 238880
β-actin 2: 238880
b2m: 12010
beta-2 microglobulin: 12010
Gapdh: 14433
glyceraldehyde-3-phosphate dehydrogenase: 14433
miR-19a: 723891"
  },
  {
    "caption": "I, J CTG assay-based quantification of luminescence signal intensity as surrogate parameter of metabolically active osteoblasts of the MC3T3-E1 cell line (I) and of hepatocytes of the HepG2 cell line (J) treated with anti-miR-19a/b, scr or veh and after stimulation with staurosporine to induce cell death as positive control. n= 6.",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "A Immunoblot of Tgif1 protein expression in calvarial osteoblasts transfected with scrambled (scr), or with anti-miR-19a, anti-miR-19b and anti-miR-19a/b (left), or with miR-19a, mir-19b and mir-19a/b mimics (right) as indicated. Immunoblot for Actin was used as loading control. Normalized fold expression and molecular weight in kilo Dalton (kD) are indicated (representative image of 3 independent experiments).",
    "ncbi_link": "miR-19a: 723891
mir-19a: 723891
miR-19b: 751527
mir-19b: 751527"
  },
  {
    "caption": "C Images of von Kossa-stained histological sections of the proximal tibiae of 12-week-old male mice of the genotypes Dmp1-Cre-;Tgif1fl/fl treated weekly with scr (n=8) or anti-miR-19a/b (n=10) and Dmp1-CreTg;Tgif1fl/fl treated weekly with scr (n=7) or anti-miR-19a/b (n=14) for 4 weeks. Scale bar indicates 1 mm. D Bone histomorphometric analysis of the proximal tibiae of the same animals as in (C). For abbreviations see legend to figure 1.",
    "ncbi_link": "Cre: 2777477
Dmp1: 13406
miR-19a: 723891
Tgif1: 21815"
  },
  {
    "caption": "A Immunoblot of Tgif1 protein expression in calvarial osteoblasts after stimulation with PTH (+) or vehicle (-) and after transfection with scrambled (scr), anti-miR-19a, anti-miR-19b or anti-miR-19a/b as indicated. Immunoblot for Actin was used as loading control. Normalized fold expression and molecular weight in kilo Dalton (kD) are indicated (representative image of 3 independent experiments).",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527"
  },
  {
    "caption": "B Images of von Kossa-stained histological sections of the proximal tibiae of 12-week-old male wild type mice after treatment with scr oligonucleotides and vehicle (veh) (n=8), anti-miR-19a/b and veh (n=10), scr and intermittent PTH (n=12) or a co-treatment with anti-miR-19a/b and PTH (n=10) for 4 weeks. Scale bar indicates 1 mm. C Histomorphometric analysis of the proximal tibiae of the same animals as in (B) after treatment with intermittent PTH or veh and/or weekly injections of anti-miR-19a/b or scr control for 4 weeks. For abbreviations see legend to figure 1.",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "D Images of von Kossa-stained histological sections of the fourth lumbar vertebral bodies of the same animals as in (B). Scale bars indicate 1 mm. E Histomorphometric analysis of the fourth lumbar vertebral body. For abbreviations see legend to figure 1, scr, veh n=8; anti-miR-19a/b, veh n= 10; scr, PTH n=12; anti-miR-19a/b, veh n=10. F Analysis of serum carboxy-terminal collagen crosslinks (CTX) in the same animals as in (B).",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "J Expression analysis of the osteoclast marker genes Trap and Cathepsin K (CatK) in bone marrow macrophages isolated from sham-operated (n=2) or ovariectomized mice treated with scr (n=3) or anti-miR-19a/b (n=3) after 4 days of differentiation.",
    "ncbi_link": "Trap: 11433
Cathepsin K: 13038
CatK: 13038
miR-19a: 723891"
  },
  {
    "caption": "C Representative images of TRAP-stained osteoclast cultures of bone marrow cells transfected with scrambled (scr) control oligonucleotide or anti-miR-19a/b (representative images of 3 independent experiments). Scale bar indicates 200 μm. D Quantification of multinucleated TRAP-positive multi-nucleated cells (MNCs) after 4 days of osteoclast differentiation of bone marrow cells transfected with scr (n=4) or anti-miR-19a/b (n=8).",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "E, F Representative images (E) and quantification of MNCs (F) after transfection with scr or anti-miR-19a/b and stimulation with conditioned medium (CM) collected from Ocy454 cells that were stimulated with vehicle (veh) or PTH (n=6). Scale bar indicates 200 μm.",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "L Immunoblot of Crtc2 protein expression in the cytoplasm and nucleus of Ocy454 cells transfected with control GapmeR or GapmeR against PP2A-Cβ and stimulated with veh or PTH. Immunoblot for Lamin A/C was used as loading control and purity control of the nuclear fraction. Normalized fold expression and molecular weight in kilo Dalton (kD) are indicated (representative image of 3 independent experiments).",
    "ncbi_link": "PP2A-Cβ: 19053"
  },
  {
    "caption": "M Immunoblot of Crtc2 protein expression in the cytoplasm and nucleus of Ocy454 cells transfected with scr or anti-miR-19a/b and stimulated with veh or PTH. Immunoblot for Lamin A/C was used as loading control and purity control of the nuclear fraction. Normalized fold expression and molecular weight in kilo Dalton (kD) are indicated (representative image of 3 independent experiments).",
    "ncbi_link": "miR-19a: 723891"
  },
  {
    "caption": "A, B Relative miR-19a (A) and miR-19b (B) expression in long bones of sham-operated (n=4) and ovariectomized (OVX) (n=4) mice. C expression of Tgif1 mRNA in long bones of sham-operated (n=11) and OVX (n=6) mice.",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527
Tgif1: 21815"
  },
  {
    "caption": "D, E Relative expression of miR-19a (D) and miR-19b (E) in Ocy454 cells upon estrogen deficiency (ED) and control (C) treatment (n=6).",
    "ncbi_link": "miR-19a: 723891
miR-19b: 751527"
  },
  {
    "caption": "H Expression of Rankl mRNA in Ocy454 cells transfected with scrambled (scr) control oligonucleotide or anti-miR-19a/b in the context of ED (n=9).",
    "ncbi_link": "miR-19a: 723891
Rankl: 21943"
  },
  {
    "caption": "(A) Representative clones screened for CD24 expression under regulation of tetracycline. The cells were exposed to 1 µg/ml tetracycline for 48 h. 20 µg from each sample were subjected to Western blot analysis for CD24 and analyzed with anti-CD24 SWA11 mAb. The membrane was reprobed with anti-tubulin antibody to assess the uniformity of sample loading.",
    "ncbi_link": "CD24: 100133941"
  },
  {
    "caption": "(D) Western blot analysis of EXO-CD24 exosomes. Tetracycline (Tet) was used to induce CD24 expression in the cell line from which exosomes are derived. HSP70 was used as an exosomal marker.",
    "ncbi_link": "CD24: 100133941"
  },
  {
    "caption": "Y-axis, z-score; X-axis, timepoints. A indicates asynchronous  cells, M mitotic  cells and the numbers represent the minutes after release from the mitotic  block). Dots show individual replicates and lines averages (n=3 for A and M; n=2 for each post-mitotic   sample). Pre-mRNA levels are shown for pluripotency genes (Oct4, Klf4, Esrrb) and cell cycle regulators (E2f1, Cdk2, Rb); mRNA levels for individual histone   genes (only averages are shown).",
    "ncbi_link": "Cdk2: 12566
E2f1: 13555
Esrrb: 26380
Klf4: 16600
Oct4: 18999
Rb: 19645"
  },
  {
    "caption": "(B) Heatmaps presented for untreated (-IAA; left) or CTCF-depleted (+IAA; right) CTCF-AID cells.",
    "ncbi_link": "CTCF: 13018"
  },
  {
    "caption": "(A) Gene expression changes (z-score) in asynchronous  cells and during  post-mitotic  release of CTCF-AID cells treated or not with IAA  to deplete CTCF  (blue, presence of CTCF; red, absence). Samples are indicated on the X-axis (A: asynchronous  cells; M: mitotic  cells; numbers: minutes since release from mitotic  block). Six gene groups are shown, based on the time  of their response to CTCF  depletion (asy, late, early) and the direction of the transcriptional change (up, down). The number of genes of each group is indicated. The yellow shadow areas indicate times  showing expression  changes. The boxplots show the median (bar), 25-75% percentiles (box) and 1.5-fold inter-quartile range (whiskers).",
    "ncbi_link": "CTCF: 13018"
  },
  {
    "caption": "(C) Average binding  profile (X-axis, reads per million) of CTCF  (top) and the Cohesin subunit SMC1   (bottom), across 8kb centred on the TSS of genes responding to CTCF  depletion exclusively in asynchronous  cells (left) or either late or early upon mitotic  release (middle and right, respectively). Interphase  is shown in blue and mitosis  in red.",
    "ncbi_link": "CTCF: 13018"
  },
  {
    "caption": "Presence of TOC proteins in the  central vacuole of protoplasts. Arabidopsis protoplasts  expressing the YFP-tagged chloroplast  proteins were analyzed by confocal microscopy following ConA  treatment for four hours. Representative images are shown (A). Chlorophyll   autofluorescence was used to determine the localization  of the YFP  fluorescence signals relative to the chloroplasts. Signals for SP1-YFP  and FAX1-YFP, which here are control proteins, were only present at the chloroplast envelope. Accumulation of YFP  puncta in the  central vacuole  is indicated by the arrowheads. Scale bar, 10 μm.",
    "ncbi_link": "YFP: "
  },
  {
    "caption": "Presence of TOC proteins in the  central vacuole of Arabidopsis leaf  and hypocotyl  cells. Eight-day-old transgenic Arabidopsis  seedlings stably expressing pToc33:YFP-Toc33  or pToc75:YFP-Toc75  were treated with ConA  for two days, and then analyzed by confocal microscopy. Accumulation of YFP  puncta in the central vacuole is indicated by the arrowheads. Scale bar, 10 μm.",
    "ncbi_link": "YFP: 
Toc33: 839248
Toc75: 823827"
  },
  {
    "caption": "Lack of TOC proteins in the  central vacuole  of atg7-2 mutant hypocotyl  cells. Eight-day-old transgenic Arabidopsis  seedlings stably expressing pToc33:YFP-Toc33  and pToc75:YFP-Toc75  in the atg7-2 mutant background were treated with ConA  for two days, and then analyzed by confocal microscopy. Note that YFP-Toc33  and YFP-Toc75  bodies (arrowheads) were retained at  plastid  bridges and extensions, and not released into the vacuole, as occurs in the WT background Scale bar, 10 μm.",
    "ncbi_link": "YFP: 
atg7: 834630
Toc33: 839248
Toc75: 823827"
  },
  {
    "caption": "Autophagy inhibition affected accumulation of TOC proteins. Eight-day-old wild-type (WT) and atg7-2 plants were treated respectively with proteasome  inhibitor, bortezomib  (Btz), cysteine protease  inhibitor, E64d, or DMSO  (Mock) for one day. Total protein extracts from these plants were analyzed by immunoblotting  using antibodies as indicated. Actin  acted as a loading control. Typical immunoblotting  results are shown (B). In B, the arrowhead indicates full-length Toc159, and the hollow arrow indicates a truncated form of Toc159. Molecular weight markers (sizes in kD) are indicated to the right of the images.",
    "ncbi_link": "atg7: 834630"
  },
  {
    "caption": "Autophagy inhibition affected accumulation of TOC proteins. Eight-day-old wild-type (WT) and atg7-2 plants were treated respectively with proteasome  inhibitor, bortezomib  (Btz), cysteine protease  inhibitor, E64d, or DMSO  (Mock) for one day. Band intensities were quantified and normalized to equivalent data for Actin  (C). Data are means ± SEM from three biological replicates. Asterisks in C indicate significance according to an unpaired two-tailed Student's t-test (*, significant at P < 0.05; **, significant at P < 0.01).",
    "ncbi_link": "atg7: 834630"
  },
  {
    "caption": "Presence of autophagosome  in the chloroplast envelope. Arabidopsis protoplasts  expressing free YFP  and YFP-ATG8  (autophagosome  marker) were analyzed by confocal microscopy. Corresponding chlorophyll  autofluorescence images were employed to orientate the YFP  signal in relation to the chloroplasts. For eliminating interference from cytosolic  signals, intact protoplasts  (upper panels) were ruptured using 10-μm nylon mesh to isolate the chloroplasts. Retention of YFP  signals in association with chloroplasts   upon rupturing the cell (lower panels) clearly indicated that the YFP-ATG8  was associated with chloroplasts. Representative images are shown (A).",
    "ncbi_link": "YFP: 
ATG8: 828287"
  },
  {
    "caption": "Presence of NBR1-HA  in chloroplast  fraction. The protoplasts  were isolated from four-week-old transgenic Arabidopsis plants stably expressing p35S:NBR1-HA  (NBR1-HA) and p35S:YFP-HA  (YFP-HA), followed by chloroplast  purification, respectively. Protein samples of whole protoplasts  and isolated chloroplasts  of NBR1-HA  and YFP-HA  were then analyzed by SDS-PAGE and immunoblotting, using antibodies against the HA  tag and Tic40. Typical immunoblotting  results are shown (G).",
    "ncbi_link": "HA: 
YFP: 
NBR1: 828571"
  },
  {
    "caption": "BiFC  results showed interaction between NBR1  and TOC proteins. cYFP and nYFP  refer to C-terminal YFP  fragment and N-terminal YFP  fragment, respectively. Reconstitution of YFP  fluorescence was assessed after transient coexpression of the indicated pairs of fusion proteins. CDKA1  and OEP7  were used as negative controls for OEM  and cytosolic proteins, respectively. Representative images are shown. Scale bars, 10 μm.­ The frequency of protoplasts  showing a BiFC  signal in C was quantified. All data are means ± SEM from three experiments.",
    "ncbi_link": "cYFP: 
nYFP: 
YFP: "
  },
  {
    "caption": "NBR1 coimmunoprecipitated  with TOC proteins. Proteins were extracted from eight­-day-old transgenic Arabidopsis  seedlings stably expressing p35S:NBR1-HA  or p35S: NBR1-ΔUBA-HA, or control seedlings only expressing p35S:YFP-HA, following UVB  treatment for four hours. Obtained protein extract was analyzed by IP  using anti-HA  resin, and analyzed by immunoblotting  of four endogenous proteins or HA-tagged proteins. Tic40  acted as negative controls. The asterisks indicate nonspecific cross-reacting bands. Arrow indicates the NBR1-HA  band. The arrowhead indicates full-length Toc159  protein. Molecular weight markers (sizes in kD) are indicated to the right of the images.",
    "ncbi_link": "HA: 
YFP: 
NBR1: 828571"
  },
  {
    "caption": "Phenotypes of seedlings  under UVB  stress. Briefly, eight-day-old WT, atg7-2, nbr1-2 and NBR1-OX (overexpressor) seedlings  grown under normal condition were subjected to UVB  stress, with UVB  treatment for 3 hours and recovery  for 7 days. Representative plant images (A) and total chlorophyll  content values (B) are shown; the latter provide a convenient metric for biomass. The chlorophyll  values for the mutants and overexpressor plants were statistically significantly different from that for the WT (Student's t test; *, significant at P < 0.05; ***, significant at P < 0.001).",
    "ncbi_link": "atg7: 834630
nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "TOC protein levels were regulated by autophagy in response to short-term UVB   stress. Eight-day-old plants of indicated genotypes were subjected to UVB  stress for the indicated times, and then analyzed by immunoblotting  using 10 μg total protein extract loaded per lane (C, upper). Coomassie staining indicated that the treatments did not change the overall protein profile (C, lower). Band intensities were quantified and normalized to equivalent Actin  data (D) Time  0 was taken as 100%. Unpaired two-tailed Student's t-tests revealed that the Toc159  protein level in nbr1-2 (P < 0.05) and NBR1-OX (P < 0.05), the Toc75  protein level in atg7-2 (P < 0.05), nbr1-2 (P < 0.01), and NBR1-OX (P < 0.05), and the Toc33  protein level in atg7-2 (P < 0.05), nbr1-2 (P < 0.01), and NBR1-OX (P < 0.05), were significantly different from levels in the WT at the time  of 1 d recovery   from UVB  stress.",
    "ncbi_link": "atg7: 834630
nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "TOC protein levels were regulated by autophagy in response to short-term heat  stress. Eight-day-old plants of indicated genotypes grown in vitro were subjected to short term heat  stress, recovered for the indicated times, and then analyzed by immunoblotting  using 10 μg total protein extract loaded per lane (B, upper). Coomassie staining indicated that the treatments did not change the overall protein profile (B, lower). Band intensities were quantified and normalized to equivalent Actin  data (C). Time  0 was taken as 100%. Data are means ± SEM from three biological replicates. Unpaired two-tailed Student's t-tests revealed that the Toc159  protein level in nbr1-2 (P < 0.05) and NBR1-OX (P < 0.01), and the Toc75  protein level in NBR1-OX (P < 0.05), were significantly different from levels in the WT at Time  12 h; and that the Toc159  protein level in atg7-2 (P < 0.001), nbr1-2 (P < 0.01), and NBR1-OX (P < 0.001), and the Toc75  protein level in atg7-2 (P < 0.01), nbr1-2 (P < 0.01), and NBR1-OX (P < 0.01), were significantly different from levels in the WT at Time  24 h.",
    "ncbi_link": "atg7: 834630
nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "Analysis of  protein import efficiency  in vitro. Chloroplasts  were isolated from 12-day-old WT, nbr1-2 and NBR1-OX seedlings  grown in vitro under normal condition, and were subjected to in vitro protein import assay by using 35S-labeled Rubisco small subunit  (SSU) precursor protein as the import substrate, followed by corresponding quantification of the maturation of the radiolabeled    precursor protein. A representative phosphor  screen image is shown (upper left), and Coomassie staining  of Rubisco large subunit (LSU) indicated equal loading (lower left); Times  indicate minutes after the start of each import reaction. IVT, in vitro translation product used as a control. Together with similar images from two additional experiments, this was used to conduct the quantitative analysis shown (right); the amount of imported, mature protein in each sample was expressed as a percentage of that present at the final  time point for the WT. Data are means ± SEM from three biological replicates.",
    "ncbi_link": "nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "Chloroplast  development in WT, nbr1-2 and NBR1-OX seedlings  under UVB  stress was studied. Cotyledons  of eight-day-old plants grown in vitro under normal condition (D) or UVB  stress (E) were analyzed by transmission electron microscopy, and representative images are shown. UVB  stress was conducted in the same procedures as in C. In D and E, the upper images are at the same magnification (scale bar, 2 μm); and below these are high magnification (5×) images corresponding to the boxed regions above. These and similar micrographs of chloroplasts were used to determine chloroplast  shape (F), the number of   thylakoid lamellae per granum  (G), and the number of starch granules  per chloroplast  (H) in each genotype, with or without UVB  stress. Asterisks indicate significance according to an unpaired two-tailed Student's t-test (*, significant at P < 0.05; ***, significant at P < 0.001; ****, significant at P < 0.0001). Values are means ± SEM from 30-50 chloroplasts.",
    "ncbi_link": "nbr1: 828571
NBR1: 828571"
  },
  {
    "caption": "Phenotypes of two-week-old WT, nbr1-2, ppi1  and ppi1 nbr1-2 seedlings  grown on soil. Representative plant images (A) and chlorophyll  contents (B) are shown. The chlorophyll  values for the ppi1  and ppi1 nbr1-2 plants were statistically significantly different (Student's t test; ****, significant at P < 0.0001). Values are means ± SEM from 20 plants.",
    "ncbi_link": "nbr1: 828571
ppi1: 828859"
  },
  {
    "caption": "Chloroplast  development in ppi1  and ppi1 nbr1-2 seedlings  was studied. Cotyledons  of two-week-old plants grown under normal condition as in A were analyzed by transmission electron microscopy, and representative images are shown (E). In E, the upper images are at the same magnification (scale bar, 1 μm); and below these are high magnification (3×) images corresponding to the boxed regions above. These and similar micrographs of chloroplasts  were used to determine chloroplast  size (F) and the number of thylakoid lamellae per granum  (G) in each genotype. Asterisks indicate significance according to an unpaired two-tailed Student's t-test (****, significant at P < 0.0001). Values are means ± SEM from 30-40 chloroplasts.",
    "ncbi_link": "nbr1: 828571
ppi1: 828859"
  },
  {
    "caption": "(a) Plasma ornithine  concentrations in Oatrhg mice  following intravenous injections of AAV-OAT  at the doses of 1x1013 (n=9) and 3x1013 genome copies (gc)/Kg (n=6), or AAV-GFP  at the dose of 1x1013 gc/Kg (n=9). Normal range was established on wild-type mice  (n=7) and average ± 2SD was calculated. Data are shown as averages ± SEM. ***p<0.001, ****p<0.0001 (Two-way ANOVA test).",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(c) Plasma ornithine  and lysine  concentrations at 12 months of age (10-months post-injection) in  Oatrhg mice injected with AAV-OAT  (n=3) or AAV-GFP  (n=3); WT mouse  controls (n=5) are also shown; each sample was analyzed as triplicates, data are shown as averages ± SEM. One-way ANOVA test with Tukey correction; *p <0.05; ****p<0.0001.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(e) Western blot for OAT  and GFP  in livers  of Oatrhg mice  injected with AAV-GFP  or AAV-OAT. A WT mouse liver  was included as control. Vinculin  was used as loading control.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(g) Liver immunohistochemistry  showing approximately 10% of OAT-positive cells in  Oatrhg mice  injected with AAV-OAT. Livers  of WT and Oatrhg mice  injected with AAV-GFP  are shown as controls. 5x (images on the left side) and 20x (images on the right side) fields of view are shown.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(h) Representative H&E staining  of the retinas  of 11-month-old Oatrhg mice  injected with AAV-GFP  or AVV-OAT  at the doses of 1x1013 or 3x1013 gc/Kg; age-matched WT mice  and uninjected Oatrhg mice  were included as controls (40X). Abbreviations: OS, outer segment; IS, inner segment; RPE,  retinal pigment epithelium; ONL, outer nuclear layer; INL, inner nuclear layer.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(a) Representative electron micrographs of the mouse retina  of an AAV-GFP  injected Oatrhg mouse  showing retinal pigmented epithelium  (RPE) and adjacent abnormal  outer segment  (OS) disk membranes (black arrows). Phagolysosomes  containing undigested OS disc membranes are present (asterisks). (b) Retina  of AAV-OAT  injected Oatrhg mice  showing  photoreceptor disk membranes  (white arrows) and RPE  ultrastructure comparable to age matched WT mice  (c, white arrows). (c) Control retina  of WT mouse  is shown as comparison.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "(a) Plasma ornithine  concentrations in AAV-GFP- (n=3) and AAV-OAT-injected (n=3) OatΔ mice. Normal range of wild-type mice  is also shown. Each value plotted represents mean ± SEM; Two-way ANOVA test, *p <0.05, **p<0.01.",
    "ncbi_link": "GFP: 
OAT: 4942
Oat: 18242"
  },
  {
    "caption": "(c) Retinal  H&E (40X) of  OatΔ mice  injected with either AAV-GFP  or AAV-OAT. Representative of three mice  per groups are shown; WT mice  were included as control. Abbreviations: OS, outer segment; IS,  inner segment; RPE, retinal pigment epithelium; ONL, outer nuclear layer; INL, inner nuclear layer.",
    "ncbi_link": "GFP: 
Oat: 18242
OAT: 4942"
  },
  {
    "caption": "mRNA expression levels of the indicated genes were assayed by real-time PCR and normalized to Actb (C).",
    "ncbi_link": "Actb: "
  },
  {
    "caption": "mRNA expression levels of the indicated genes were assayed by real-time PCR and normalized to Actb (C).",
    "ncbi_link": "Actb: "
  },
  {
    "caption": "Flag-PGC-1α was introduced into PGC-1α knockdown brown preadipocytes for 24 h and samples were collected for western blotting analyses of the indicated proteins (D). Expression levels of the indicated proteins were quantified (E) (mean ± SEM; n=3). Scramble, scramble shRNA.",
    "ncbi_link": "Flag: 
PGC-1α: 19017"
  },
  {
    "caption": "Samples were collected for real-time PCR analysis. The expression of Fundc1 was normalized (F).",
    "ncbi_link": "Fundc1: 72018"
  },
  {
    "caption": "(G-H) Scramble and PGC-1α knockdown preadipocytes were induced to differentiate into mature adipocytes and samples were collected for western blotting analyses (G) and quantification of the indicated proteins (H)",
    "ncbi_link": "PGC-1α: 19017"
  },
  {
    "caption": "(B) Luciferase activity stimulated by the human Fundc1 promoter. The activity of Fundc1 promoter fragments, either wild type (WT) or with a mutation in the potential NRF1 binding site, was assayed using a dual luciferase reporter system.",
    "ncbi_link": "Luciferase: 
Fundc1: 139341"
  },
  {
    "caption": "(C,D) EMSA assay using biotinylated oligonucleotide probes containing the predicted NRF1 binding site or mutant NRF1 binding site in the promoter of Fundc1 (F1 probe or mut F1 probe) ,the confirmed NRF1 binding site in the promoter of VSNL1 (positive probe). The probes were incubated with HeLa nuclear extracts, then run on a gel (C). A super-shifted band (asterisk) is detected in the presence of an anti-NRF1 antibody (D). Labeled probe: biotin labeled wild type Fundc1 probe; Cold probe: wild type Fundc1 probe; Mut probe: NRF1 binding site mutant Fundc1 probe; asterisk indicates the supershifted band generated with antibody to NRF1.",
    "ncbi_link": "Fundc1: 139341
VSNL1: 139341"
  },
  {
    "caption": "(E,F) ChIP assay to analyze the interaction of NRF1 (E) or PGC-1α (F) proteins with the Fundc1 promoter.",
    "ncbi_link": "Fundc1: 139341"
  },
  {
    "caption": "(G) NRF1-myc was introduced into NRF1 shRNA knockdown cells for 24 h and scramble cells were used as control and samples were collected for western blotting with the indicated antibodies. (H) Scramble and NRF1 shRNA knockdown cells were transfected with vector and PGC-1α-Flag for 24 h and samples were collected for western blotting with the indicated antibodies. ",
    "ncbi_link": "Flag: 
myc: 
NRF1: 4899
PGC-1α: 10891"
  },
  {
    "caption": "(I) ChIP analysis of the interaction of PGC-1α protein with the Fundc1 promoter in scramble or NRF1 shRNA knockdown cells.",
    "ncbi_link": "Fundc1: 139341
NRF1: 4899"
  },
  {
    "caption": "(A,B) BATs isolated from Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucp1cre+ (Cre+) mice at 30℃ or following 72 h at 4℃ were analyzed by transmission electron microscopy. Representative images are shown, scale bar, 1μm (A). The number of mitophagosomes per 100 mitochondria were counted and normalized (B).",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Fundc1: 72018
Ucp1: 22227"
  },
  {
    "caption": "(C,D).Representative fluorescence images of BAT sections from Fundc1fl/fl/Adiponectincre- (Cre-) and Fundc1fl/fl/Adiponectincre+ (Cre+) mito-Keima mice at normal conditions (30℃) or 4℃ for 72 h. Scale bar, 50 μm (C). Quantification of the ratio between red and green signals (D).",
    "ncbi_link": "Adiponectin: 11450
cre: 2777477
Cre: 2777477
Fundc1: 72018"
  },
  {
    "caption": "(E) Fundcfl/fl/Ucp1cre- (Cre-) and Fundcfl/fl/Ucpcre+ (Cre+) mice were maintained at 30℃ (Normal) or exposed to 4℃ for 72 h (Cold). Mitochondrial DNA copy numbers were analyzed by null and normalized to nuclear DNA standards.",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Fundc: 72018
Ucp: 22227
Ucp1: 22227"
  },
  {
    "caption": "(F) The relative total mito-keima signal (green signal ) in Fundc1 deficiency and control mito-keima mice under normal condition or cold exposure were quantified and plotted.",
    "ncbi_link": "Fundc1: 72018"
  },
  {
    "caption": "(G) BATs isolated from Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucp1cre+ (Cre+) at 30℃ or following 72 h at 4℃ were analyzed by transmission electron microscopy. The percent of mitochondria without cristae is shown in the histogram.",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Fundc1: 72018
Ucp1: 22227"
  },
  {
    "caption": "Oxygen consumption rate (OCR) (H) were measured in BAT from Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucpcre+ (Cre+) mice kept at 30℃ or at 4℃ for 72 h.",
    "ncbi_link": "Cre: 2777477
cre: 2777477
Fundc1: 72018
Ucp: 22227
Ucp1: 22227"
  },
  {
    "caption": "mitochondrial superoxide (I) were measured in BAT from Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucpcre+ (Cre+) mice kept at 30℃ or at 4℃ for 72 h.",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Fundc1: 72018
Ucp: 22227
Ucp1: 22227"
  },
  {
    "caption": "(A) Body temperature measurements in Fundc1fl/fl/Ucp1cre- (Cre-) and Fundc1fl/fl/Ucp1cre+ (Cre+) fasting male mice before and during cold exposure (4°C) for the indicated time. Body temperature (B) before and after 72 h cold exposure (4°C) of Cre- and Cre+ male mice.",
    "ncbi_link": "cre: 2777477
Cre: 2777477
Fundc1: 72018
Ucp1: 22227"
  },
  {
    "caption": "BAT tissue weight (C) measurements before and after 72 h cold exposure (4°C) of Cre- and Cre+ male mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Fundc1fl/fl/Ucpcre- and Fundc1fl/fl/Ucp1cre+ mice were exposed to 4℃ for 72 h (Cold), and control mice were kept at 30℃ (Normal). Western blotting analysis of BAT protein levels (D). Protein expression levels were normalized to Actin (E).",
    "ncbi_link": "cre: 2777477
Fundc1: 72018
Ucp: 22227
Ucp1: 22227"
  },
  {
    "caption": "Fundc1fl/fl/Ucpcre- and Fundc1fl/fl/Ucp1cre+ mice were exposed to 4℃ for 72 h (Cold), and control mice were kept at 30℃ (Normal). Levels of mRNAs encoding Fundc1 and Ucp1 were measured by real-time PCR and normalized to Actb (F).",
    "ncbi_link": "Actb: 
cre: 2777477
Fundc1: 72018
Ucp: 22227
Ucp1: 22227"
  },
  {
    "caption": "(G) Representative images of UCP1 immunohistochemistry of BAT sections from Cre- or Cre+ mice in normal conditions (30℃) or following 72 h at 4℃. Scale bar, 50 μm.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Sanger sequencing of the germline NF1 mutation c.350T>A present in the patient that developed two different tumors (MPNST-NF1-001 and MPNST-NF1-002). Sequencing results from normal tissue, primary tumor (PT), and orthotopic xenograft tumors (OT) are shown. The sequence of the NF1 region revealed WT NF1 alleles in primary tumor samples, and not in the corresponding derived orthoxenografts, indicating probable loss of the human stromal cells.",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "SNP array of primary tumor (PT) and orthotopic xenograft passages 1 (OT P1) and 4 (OT P4) for MPNST-NF1-001 and MPNST-NF1-002 tumors. Results correspond to chromosome 17. Images show the B-allele frequency (BAF) for the different samples as scatter plots and the copy number callings below them represented by thick horizontal lines: 2n regions are shown in gray, gained regions in orange, lost regions in green, and LOH regions are represented in blue. The vertical red line indicates the location of the NF1 locus. In addition, the percentage of tumor versus stromal cells for each sample is represented in a pie chart (blue, stromal cells; red, tumor cells).",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "(F) Representative images of GFP-positive HEK293  cells at day 7 post-transduction using 1x106 TU/cell of RGD4C.TPA.GFP   or RGD4C.AAVP.GFP   particles. Non-targeted (NT) particles were included as control. Data shown are representative of five independent experiments, performed each in triplicates. Scale bar, 100 μm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) Quantification of gene expression in HEK293  cells after transduction with 0.5x106, 1x106, and 2x106 TU/cell of RGD4C.TPA, RGD4C.AAVP  or non-targeted (NT) particles carrying Lucia.  Luciferase activity was measured at days 1 to 6 post-transduction. Data shown are representative of three independent experiments (n = 3), and are expressed as mean + SEM. One-way ANOVA with Tukey's HSD test was used for data analysis.",
    "ncbi_link": "Lucia: "
  },
  {
    "caption": "(F) Quantification of Lucia reporter  gene expression following transduction of human  primary SEBTA003 glioblastoma  and G26 glioblastoma-derived  neural stem cells  with 1x106 TU/cell. Data are expressed as mean + SEM of n = 3 independent experiments. One-way ANOVA with Tukey's HSD test was used for data analysis.",
    "ncbi_link": "Lucia: "
  },
  {
    "caption": "(G) 3D primary GBM001   tumor spheres subjected to transduction by increasing doses of TPA  and AAVP  encoding Lucia. Experiments were repeated three times and performed in triplicates. Data are shown as mean + SEM and are representative of one experiment. Independent t-test was used for data analysis.",
    "ncbi_link": "Lucia: "
  },
  {
    "caption": "(B) ELISA  quantification of TNFα production in media collected on days 3 to 5 post-transduction of human  primary GBM001 tumor spheres at 1x106 TU/cell of targeted (RGD4C) or non-targeted (NT) TPA  particles carrying native TNFα or recombinant TNFαIL2 sequences. Data are representative of one experiment and expressed as mean + SEM. Experiments were repeated twice in triplicates, one-way ANOVA with Tukey's HSD test was used for data analysis.",
    "ncbi_link": "IL2: 3558
 TNFα: 7124
TNFα: 7124"
  },
  {
    "caption": "(C) Biodistribution of gene delivery upon intravenous administration of 5x1010 TU of NT or RGD4C.TPA.TNFαIL2 to NOD/SCID mice  bearing subcutaneous human GBM001. Tumors and healthy organs were harvested at day 18 post-transduction and analysed using RT-qPCR to quantify the TNFαIL2  transcripts. Data shown are expressed as mean + SEM, from n = 3 mice. Two-way ANOVA was used for data analysis.",
    "ncbi_link": "IL2: 3558
TNFα: 7124"
  },
  {
    "caption": "(D) BLI  of Luc  showing representative mice with subcutaneous  GBM001 labelled with Luc gene, at day 18 post targeted TNFαIL2 cytokine treatment. (E) Analysis of tumor growth in representative mice, from D, using the tumor bioluminescence  data (total flux) and expressed as fold changes of tumor luminescence flux  at different time points compared to day 0.",
    "ncbi_link": "Luc: 
IL2: 3558
TNFα: 7124"
  },
  {
    "caption": "(B) Investigation of the TPA.IL15IgK in comparison to the native TPA.IL15   in  B16.F1  and CT26.CL25 tumor cells. The TPA  DNA constructs were transfected into tumor cells, then the bioactivity  of secreted  IL15   was assessed by evaluating the effects of media from transfected cells on the proliferation  of mouse CTLL-2. Data are representative of one experiment and expressed as mean + SEM. Experiments were repeated twice and performed in triplicates, one-way ANOVA with Tukey's HSD test was used for data analysis",
    "ncbi_link": "IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(C) Targeted (RGD4C) and non-targeted (NT) TPA  particles carrying  IL15IgK were produced and used to transduce B16.F1   or CT26.CL25 cells at 0.5x106 or 1x106 TU/cell. Then secreted IL15   was quantified by ELISA  in tumor cell media collected on day 5 post-transduction. RGD4C.TPA  without  IL15IgK (mock) was also included as control. Experiments were repeated twice and shown are the results from a representative experiment. Data are expressed as mean + SEM, one-way ANOVA with Tukey's HSD test was used for data analysis.",
    "ncbi_link": "IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(D) Evaluation of CTLL-2 proliferation  in the presence of media collected from  B16.F1 or CT26.CL25  tumor cells after transduction with TPA  particles carrying IL15IgK. Cells treated with a recombinant IL2  cytokine were included as a positive control. Data are representative of one experiment, expressed as mean + SEM and shown as change in CTLL-2 number relative to treatment initiation day. Experiments were repeated twice and in triplicates, one-way ANOVA with Tukey's HSD test was used to analyse the data.",
    "ncbi_link": "IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(A) Tumor-bearing BALB/c mice  with established subcutaneous CT26.CL25 tumors  were intravenously injected with a single dose, 5x1010 TU/mouse, of targeted (RGD4C) or non-targeted (NT) TPA.IL15IgK. Gene delivery was evaluated by quantifying the IL15IgK mRNA expression  in tumors  and healthy tissues at day 5 post TPA  administration. Data are representative of one experiment, n = 3, and expressed as mean + SEM. Two-way ANOVA test was used for data analysis.",
    "ncbi_link": "IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(B) Safety of dose escalation regimens assessed at day 5 following TPA  delivery, by evaluating the serum  levels of LDH  from n = 2 mice/TPA  dose of targeted (RGD4C) or non-targeted (NT) TPA.IL15IgK. Serums  from untreated mice  were also analysed.",
    "ncbi_link": "IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(C) Representative tumor-bearing mice  showing bioluminescence  imaging  of luciferase  on days 0 and 5 post administration with 5x1010 TU of RGD4C.TPA.IL15IgK (RGD4C) or non-targeted (NT) particles. The CT26.CL25 tumor cells stably express a luciferase Luc  reporter gene. Untreated mice  were also included as controls (CTRL).",
    "ncbi_link": "Luc: 
luciferase: 
IgK: 243469
IL15: 3600"
  },
  {
    "caption": "(A) The immune profile of CT26.CL25  tumors was investigated using  RT-qPCR at day 5 after TPA.IL15IgK administration. A panel of immunological mRNA transcripts were selected for analysis and included CD8a  and CD8b  as markers for CD8+ T cell  population; NKp46  for NK  cell population. Markers for cytotoxic cell-killing by CD8+ T cells (GZMa, GZMb) and by NK  cells (Prf1) were also analysed. Expression  of TBX21  was evaluated as a marker for the Th1 response mediated by interferon gamma  (IFN-γ), and FoxP3  for  Treg  cells. Data shown are representative of n = 5 mice  and expressed as mean + SEM. Non-parametric Mann-Whitney test was used for GZMb  and TBX2 data analysis, and independent t-test to analyse data of the other markers.",
    "ncbi_link": "CD8a: 12525
CD8b: 12526
FoxP3: 20371
GZMa: 14938
GZMb: 14939
IgK: 243469
IL15: 3600
NKp46: 17086
Prf1: 18646
TBX2: 57765
TBX21: 57765"
  },
  {
    "caption": "(B) TPA  particles encoding IL12 were used to treat immunocompetent BALB/c mice  bearing subcutaneous CT26.CL25 tumors labelled with a Luc  reporter gene. Representative tumor-bearing mice  at day 5 post-treatment with targeted RGD4C.TPA.IL12  (RGD4C) or non-targeted TPA.IL12  (NT).",
    "ncbi_link": "Luc: 
IL12: 16160"
  },
  {
    "caption": "(C) Analysis of total flux change in tumors, n = 4 mice, after IL12 immunotherapy. The central band represents the median of the data. The boxes upper and lower lines represent quartile 3 and quartile 1 of the data, respectively. The whiskers represent the maximum and minimum outliers of the data. Non-parametric Mann-Whitney test was used for data analysis.",
    "ncbi_link": "IL12: 16160"
  },
  {
    "caption": "(E) Serial quantification of  IL12 in media of B16.F10 cells treated with RGD4C.TPA.IL12 or controls. Data are representative of one experiment, n = 3 biological repeats, and shown as mean + SD Experiments were repeated three times. One-way ANOVA with Tukey's HSD test was used for data analysis.",
    "ncbi_link": "IL12: 16160"
  },
  {
    "caption": "(F) RGD4C.TPA.IL12  immunotherapy of subcutaneous  B16.F10 tumors in C57BL/6 mice  (n = 4). Data are shown as mean + SEM independent t-test was used for data analysis. Tumor volume changes are shown over time.",
    "ncbi_link": "IL12: 16160"
  },
  {
    "caption": "(B) Western blot analysis of lysates and media from wt and mutant N9 cells (N9 wt /mu) using antibody anti-murine TREM2 (clone 5F4), which is raised against the murine TREM2 extracellular domain. sTREM2, soluble TREM2* Indicate unspecific bands. Anti-calnexin antibody was used as loading control.",
    "ncbi_link": "TREM2: 83433"
  },
  {
    "caption": "(D) Western blot of BMDM derived from wt and Trem2 knockout (ko) animals using antibody 5F4.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(E) Phagocytosis of fAβ42 by BMDM from wt and Trem2 ko animals in the presence or absence of 2D8, or the non-binding control antibody 6687. (n = 3, +/- SEM; 2 way ANOVA, interaction P=0.0005, genotype P<0.0001, treatment P<0.0001; post hoc tests wt vs. ko for the following conditions: fAβ42 P=0.0021, fAβ42-2D8 1 µg/ml P<0.0001, fAβ42-2D8 5 µg/ml P<0.0001, fAβ42-2D8 10 µg/ml P<0.0001, fAβ42/6687 10 µg/ml P=0.0007)(F) Quantification of relative fAβ42uptake to lowest antibody concentration used.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(G) Phagocytosis of fAβ42 by BMDM from wt and Trem2 ko animals in the presence or absence of mAb11, or an isotype control antibody (IC). (n = 4, +/- SEM; 2 way ANOVA, interaction P=0.0223, genotype P<0.0001, treatment P<0.0001; post hoc tests wt vs. ko for the following conditions: fAβ42-mAb11 1 µg/ml P=0.0391, fAβ42-mAb11 5 µg/ml P=0.0069, fAβ42-mAb11 10 µg/ml P<0.0001, fAβ42-mAb11 20 µg/ml P=0.0001, fAβ42-mAb11 50 µg/ml P<0.0001).(H) Quantification of relative fAβ42 uptake to lowest antibody concentration used.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(I) Recombinant mousesTREM2 does not rescue fAβ42 uptake in Trem2-deficient BMDM. Increasing amounts of sTREM2 were added to the media of wt or Trem2 ko BMDM in the presence or absence of mAb11 (10 µg/ml).",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(K) Phagocytosis of fAβ42 by primary microglia from wt and Trem2 ko animals in the presence or absence of mAb11, or an isotype control antibody (IC). (n = 5, +/- SEM; 2 way ANOVA, interaction P=0.4797, genotype P<0.0001, treatment P<0.0001; post hoc tests wt vs. ko for the following conditions: fAβ42-mAb11 5 µg/ml P=0.0449, fAβ42-mAb11 10 µg/ml P=0.0370, fAβ42-mAb11 20 µg/ml P=0.0299, fAβ42-mAb11 50 µg/ml P=0.0120).(L) Quantification of relative fAβ42uptake to lowest antibody concentration used.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(A) Representative histograms for Fcγ-receptors-PE (FcγR-PE) expression levels as used for quantification. Stacked histograms for log PE fluorescence intensity of wt and Trem2 ko BMDM are shown for the respective FcγR (I, IIB/III and IV).(B) Relative quantification of cell surface levels of FcγR molecules. Absolute number of cell surface FcγR-PE molecules was determined by the BD QuantiBRITE® method (see methods section for details) and normalized to expression levels of the respective wt control. (n=4, +/- SEM, t test, two-tailed; wt vs. ko: FcγRI-PE P=0.0008, FcγRIIB/III-PE P=0.0033, FcγRIV-PE P=0.7001).",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(C) mRNA levels of FcγR are increased in Trem2 ko BMDM. Fold changes of the respective FcγR (I, IIB, III, IV) mRNA levels in Trem2 ko BMDM were determined by quantitative real-time PCR. (n=6, +/- SEM; one-sample t test, two-tailed; wt vs. ko: FcγRI P=0.0118, FcγRIIB P=0.0006, FcγRIII P=0.0004, FcγRIV P=0.0284)",
    "ncbi_link": "FcγRI: 14129
FcγRIIB: 14130
FcγRIII: 14131
FcγRIV: 246256
Trem2: 83433"
  },
  {
    "caption": "(D) Phosphorylated Syk (P-Syk) and total Syk (T-Syk) levels were determined by western blotting in lysates from wt and Trem2 ko BMDM after 1 h treatment with Aβ alone, together with antibody 2D8 (Aβ-2D8), or an isotype control (Aβ-IC). Actin was used as a loading control.(E) Quantification of P-Syk normalized to T-Syk. (n = 4, +/- SEM; 2 way ANOVA, interaction P=0.0490, genotype P=0.0898, treatment P<0.0001. Bonferroni-corrected pair-wise post hoc tests, ** P =0.0075 vs. wt).",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(A) BMDM from wt or Trem2 ko mice were cultured on APP/PS1micebrain cryosections incubated with or without mAb11 (1 µg/ml) or an isotype control (IC; 1 µg/ml) for 24 h. Sections were then probed with methoxy-X04. Scale bar, 500 µm.(B) The amyloid plaque load was quantified from the entire sagittal section. Sections incubated with medium (no cell) were set as baseline. (n = 6, +/- SEM; 2 way ANOVA, interaction P<0.0001, genotype P<0.0001, treatment P<0.0001; Tukey's multiple comparisons tests; wt vs. ko for the following conditions: no antibody P=0.0304, IC P=0.0049, mAb11 P=0.0212; wt : IC vs. wt : mAb11 P=0.0008; ko : IC vs. ko : mAb11 P=0.0001).",
    "ncbi_link": "APP: 351
PS1: 5663
Trem2: 83433"
  },
  {
    "caption": "(C, D) Equal numbers of wt and Trem2 ko BMDM were added and cell numbers were analyzed after termination of experiments by quantifying the CD68 positive cells on top of the sections. (n = 4, +/-SEM; t-test; n.s., nonsignificant, P=0.5004). Scale bar, 200 µm.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "(A) Cryosections from unfixed brain of 6-months old APP/PS1mice were pre-incubated with increasing concentrations of mAb11 (0.001, 0.01, 0.1, 1, 5 µg/ml). BMDM from wt or Trem2 ko mice were added for 24 h. Sections were stained with methoxy-X04. Scale bar, 500 µm.(B) Methoxy-X04 signals were quantified from the entire sagittal section. (n = 5, +/- SEM; 2 way ANOVA, interaction P=0.0082, genotype P<0.0001, treatment P<0.0001. Fisher's LSD post hoc comparisons; * show statistics between wt and ko under the same experimental condition. # in black show wt compares to no antibody stimulation; # in grey show ko compares to no antibody stimulation; wt vs. ko for the following conditions: no antibody P=0.0053, mAb11 0.001 µg/ml P=0.0003, mAb11 0.01 µg/ml P<0.0001, mAb11 0.1 µg/ml P=0.0001, mAb11 1 µg/ml P=0.0007, mAb11 5 µg/ml P=0.0011; Following conditions compare to wt / no antibody: wt / mAb11 0.01 µg/ml P=0.0166, wt / mAb11 0.1 µg/ml P=0.0002, wt / mAb11 1 µg/ml P<0.0001, wt / mAb11 5 µg/ml P<0.0001; Following conditions compare to ko / no antibody: ko / mAb11 0.1 µg/ml P=0.0099, ko / mAb11 1 µg/ml P<0.0001, ko / mAb11 5 µg/ml P<0.0001.",
    "ncbi_link": "APP: 351
PS1: 5663
Trem2: 83433"
  },
  {
    "caption": "C, DNA content profiles of BAT1 and bat1Δ cells from asynchronous cultures, in SMM medium. Where indicated, exogenous amino acids were added at 1mM final concentration. On the x-axis of the histograms is fluorescence per cell, while on the y-axis is the cell number. Peaks corresponding to cells in G1 with unreplicated (1N) and cells in G2 and M phases with fully replicated (2N) DNA are indicated. The percentage of cells with G1 DNA content (%G1) from 3 independent measurements is shown in each case (mean and sd).",
    "ncbi_link": "BAT1: 856615
bat1: 856615"
  },
  {
    "caption": "B, Immunoblots of total cell extracts from asynchronous BAT1 and bat1Δ cells, from four independent experiments. The signal from Pgk1 (α-Pgk1) is shown on the blot at the bottom, and from phosphorylated Rps6 (α-Rps6-P) is on the blot above, indicated for two exposures (2 min, top; 20 sec, middle).",
    "ncbi_link": "BAT1: 856615
bat1: 856615"
  },
  {
    "caption": "D, Exogenous addition of valine leads to sustained activation of TORC1 and phosphorylation of Rps6 in cells lacking Bat1. Wild type (BAT1+) and bat1∆ (two independent isolates, #4, and #5) strains were grown overnight in minimal (SMM) medium, diluted to 1E+06 cells/mL in fresh SMM media containing the indicated amino acid (at 1mM), and harvested when they reached 5E+06 cells/mL. The levels of phosphorylated Rps6 (α-Rps6-P) and Pgk1 (α-Pgk1) are shown in immunoblots from total cell extracts in each case. The relative levels of Rps6-P/Pgk1 are shown in each case at the bottom. The boxplot graphs were generated with R language functions. Each box is drawn from the first to the third quartile, with a horizontal line drawn in the middle to denote the median. The whiskers show the interquartile range (IQR), and they were drawn at 1.5xIQR. The replicates were all biological ones.",
    "ncbi_link": "bat1: 856615
Bat1: 856615
BAT1: 856615"
  },
  {
    "caption": "A‐F′ Confocal fluorescent images of wild‐type (A, C, E) and mtm‐3(tm4475) (B, D, F) embryos at the 1.5‐fold stage stained by DAPI (A-F) and anti‐SQST‐1 (A′, B′), anti‐SEPA‐1 (C′, D′) or anti‐LGG‐1 (E′, F′) antibodies. Scale bars: 5 μm.",
    "ncbi_link": "mtm‐3: 175490"
  },
  {
    "caption": "G Western blot analysis of LGG‐1‐I and LGG‐1-II (lipidated) in wild type, epg‐6, and mtm‐3.",
    "ncbi_link": "epg‐6: 189705
mtm‐3: 175490"
  },
  {
    "caption": "H mtm‐3 and epg‐6 mutant L1 larvae have shortened mean and maximum life span in the absence of food. At least 300 animals were scored each day.",
    "ncbi_link": "epg‐6: 189705
mtm‐3: 175490"
  },
  {
    "caption": "A-C Fluorescent images of wild‐type embryos (1.5‐fold stage) expressing GFP::MTM‐3 (A), GFP::MTM‐3(C459S) (B), or GFP::MTM‐3(C459S, del PH‐G) (C).",
    "ncbi_link": "MTM‐3: 175490"
  },
  {
    "caption": "D‐G″ Confocal fluorescent images of wild‐type (D‐D″), mtm‐3 (E‐E″), atg‐2 (F‐F″), and vps‐34 (G‐G″) embryos at the 200‐cell stage expressing GFP::MTM‐3(C459S) and stained by anti‐LGG‐1 antibody. Insets show magnified views. Arrows indicate overlapping GFP and LGG‐1 puncta. Scale bars: 5 μm.",
    "ncbi_link": "atg‐2: 180949
mtm‐3: 175490
vps‐34: 172280"
  },
  {
    "caption": "H, I Number of GFP::MTM‐3(C459S)‐positive puncta and co‐localization of GFP::MTM‐3(C459S)‐ and LGG‐1‐positive puncta in various strains [mtm‐3(tm4475), atg‐2(bp576), lgg‐1(bp500), vps‐34(h797)]. At least 10 (I) and 15 (H) embryos were scored per strain. Data are shown as mean ± SD. Data from different mutant backgrounds were compared with wild type. **P 0.0001; N.S.: not statistically different.",
    "ncbi_link": "atg‐2: 180949
lgg‐1: 174050
mtm‐3: 175490
vps‐34: 172280"
  },
  {
    "caption": "J MTM‐3 but not MTM‐3(C459S) exhibits phosphatase activity toward PtdIns3P and PtdIns(3,5)P2 in vitro.",
    "ncbi_link": "MTM‐3: 175490"
  },
  {
    "caption": "J-L TEM analysis of embryos in wild type (I) and mtm‐3(tm4475) (J, K). Double‐membrane autophagosomes (arrows) were observed in mtm‐3 but not wild‐type embryos. Scale bars: 500 nm.",
    "ncbi_link": "mtm‐3: 175490"
  },
  {
    "caption": "A-H Fluorescent images of embryos at the 4‐fold stage in the indicated strains expressing ATG‐18::GFP (A-D), ATG‐18(FKKG)::GFP (E, F), or ATG‐18(FTTG)::GFP (G, H).",
    "ncbi_link": "ATG‐18: 179246"
  },
  {
    "caption": "I Confocal fluorescent images of 4‐fold mtm‐3 embryos expressing ATG‐18::GFP (I′) and stained by DAPI (I) and anti‐LGG‐1 (I″) antibody. Insets show magnified views. Arrows indicate ATG‐18 puncta labeled by anti‐LGG‐1 antibody. Scale bars: 5 μm.",
    "ncbi_link": "ATG‐18: 179246
mtm‐3: 175490"
  },
  {
    "caption": "A Relative  mRNA expression levels of  H2A.B in  L1236, L428, HDLM2 HL cell lines and Germinal centre B lymphocytes (GC) compared to the Ramos B lymphocyte cell line. The results are presented as the mean ± SD of three biological replicates.",
    "ncbi_link": "H2A.B: 474381///83740///474382"
  },
  {
    "caption": "E H2A.B interacts with RPA194 in live cells. Western blot analysis was performed to detect  RPA194  in the BioID  samples from L1236  cells (left panel), and L428  cells (right panel). The samples were prepared using  pull-down with streptavidin beads from the cell lysate of the empty vector, BirA*-H2A.B  and H2A.B-BirA* transduced cells, which were preincubated with 50 µM biotin  for 24 h. The positive control was loaded as 1% input.",
    "ncbi_link": "BirA: 948469
H2A.B: 474381///83740///474382"
  },
  {
    "caption": "B Cell proliferation assay in the presence (shNTC) or during depletion of H2A.B (shH2A.B). The results are presented as mean ± SD for five biological replicates. The significance of the difference was determined by Student's t test and denoted as ns (not significant); **, p < 0.01; ***, p<0.001.",
    "ncbi_link": "H2A.B: 474381///83740///474382"
  },
  {
    "caption": "E Genome browser screen shots of gene examples (RPs RPLP1 and RPL23A, and HDAC5 and TAF10) that contain H2A.B at their promoters identified by the CUT&RUN peak calling and whose expression  decreased significantly following H2A.B  knockdown in the RNA-seq  analysis. Green and purple indicates L1236 and  L428cells, respectively.",
    "ncbi_link": "H2A.B: 474381///83740///474382
HDAC5: 10014
RPL23A: 6147
RPLP1: 6176
TAF10: 6881"
  },
  {
    "caption": "B Differential exon usage of the CD44 gene. C.  Differential exon usage of the RPL17 gene. ",
    "ncbi_link": "CD44: 960
RPL17: 6139"
  },
  {
    "caption": "D, E Two examples show increased accessibility at the promoter peak (NXF1) (D) and decreased accessibility at the peak across the intron-exon boundary (KDM4A) (E), respectively.",
    "ncbi_link": "KDM4A: 9682
NXF1: 10482"
  },
  {
    "caption": "MITOL-KO MEFs was vulnerable to ER stress. Control MEFs (MITOLF/F) and MITOL-KO MEFs (MITOL-/-) were treated with DMSO as control, 0.8 µM thapsigargin (Tg), 0.7 µg/mL tunicamycin (Tu) or 1.2 µg/mL brefeldin A (Br) for 24 hours. All experiments using Tu below were performed at concentration of 0.7 µg/mL. The relative cell viability shows a ratio between the survival of MEFs in the absence and presence of ER stress inducers. Viable cells were detected by cell viability assay using cell counting kit-8.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL KO increased ER stress-induced apoptosis. MEFs were treated with indicated ER stress inducers at same concentration as Figure 1A for 18 hours and stained with Annexin V-FITC for the detection of apoptosis using flow cytometry.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL re-expression in MITOL-KO MEFs rescued ER stress vulnerability. MEFs were transfected with MITOL-coding vector (WT), MITOL C65/68S-coding vector (CS), or empty vector (Vec) 24 hours prior to Tu treatment for 18 hours, followed by immunoblotting with indicated antibodies. Cleaved caspase-3 (cC3) and cleaved PARP (cPARP) were used as apoptosis markers.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL KO enhanced ER stress-induced Bax translocation and cytochrome c release. Mitochondria or cytosol fraction was isolated from MEFs treated with Tu for 18 hours, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL KO induced excessive mitochondrial depolarization by ER stress. MEFs transfected with indicated vectors were treated with Tu for 18 hours and then stained with TMRM, followed by flow cytometric analysis.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "IRE1α inhibition compensated MITOL-KO MEFs for vulnerability to ER stress. MEFs were transfected with scramble or siIRE1α (#1, #2). After 24 hours, these MEFs were exposed with Tu for 24 hours , followed by immunoblotting with indicated antibodies. Error bars represent SD (n=3).",
    "ncbi_link": "IRE1α: 78943
MITOL: 69104"
  },
  {
    "caption": "MITOL KO did not affect the autophosphorylation of IRE1α. MEFs were exposed with Tu for indicated periods and phosphorylated IRE1α was detected by immunoblotting after Phos-tag SDS-PAGE.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL KO enhanced RIDD and xbp1 splicing. MEFs were incubated with Tu for 4 hours. Expression levels of various UPR associated genes were determined by qRT-PCR",
    "ncbi_link": "MITOL: 69104
xbp1: 22433"
  },
  {
    "caption": "MITOL KO enhanced RIDD and xbp1 splicing. MEFs were incubated with Tu for 4 hours. MEFs were transfected with either miR-17 or miR-34 luciferase reporter vector 24 hours prior to Tu treatment for 4 hours, followed by luciferase reporter assay (F). Error bars represent SD (n=3).",
    "ncbi_link": "luciferase: 
MITOL: 69104
miR-17: 723905
miR-34: 723848
xbp1: 22433"
  },
  {
    "caption": "IRE1α-mediated JNK phosphorylation was prolonged by MITOL KO. MEFs were incubated with Tu for indicated periods and phosphorylated JNK was detected by immunoblotting with indicated antibodies. Error bars represent SD (n=3).",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "JNK inhibition reduced ER stress-induced apoptosis of MITOL-KO MEFs. MEFs were treated with 20 µM JNK inhibitor-II (JNK inh) 2 hours prior to Tu treatment for 24 hours, followed by immunoblotting with indicated antibodies. Error bars represent SD (n=3).",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL KO facilitated IRE1α oligomerization. MEFs were transfected with IRE1α-GFP expression vector for 24 hours prior to Tu treatment for indicated periods (A). The right panels show 5-fold magnification images of the boxed regions. Percentages of cells with IRE1α-foci were calculated from 100 cells by visual inspection in each independent experiment (A). To evaluate the oligomerization level of endogenous IRE1α, cells without any transfection were solubilized and separated by sucrose density-gradient centrifugation, followed by immunoblotting with anti-IRE1α antibody (B).",
    "ncbi_link": "GFP: 
IRE1α: 2081
MITOL: 69104"
  },
  {
    "caption": "IRE1α oligomers were stabilized by MITOL KO. MEFs transfected with IRE1α-GFP were treated with Tu. After 4 hours, these cells were washed with PBS and subsequently re-fed with fresh media for indicated periods. The right panels show 5-fold magnification images of the boxed regions. Percentages of cells with IRE1α-foci were calculated from 100 cells by visual inspection at indicated periods after wash out of Tu in each independent experiment. Scale bar represents 10 µm.",
    "ncbi_link": "GFP: 
IRE1α: 2081
MITOL: 69104"
  },
  {
    "caption": "Sustained IRE1α autophosphorylation after wash out of Tu in MITOL-KO MEFs. MEFs were treated with Tu for 4 hours and washed with PBS and re-fed with fresh media for indicated periods, following by immunoblotting anti-IRE1α antibody after Phos-tag SDS-PAGE. Error bars represent SD (n=3).",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL deletion promoted the interaction between IRE1α and BIM under ER stress. MITOL-depleted HEK293 cells (KO) were generated using CRISPR-Cas9 system. Cells were co-transfected with indicated vectors 24 hours prior to Tu treatment for 12 hours. Cells were immunoprecipitated with anti-FLAG antibody, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "CRISPR: 
MITOL: 54708"
  },
  {
    "caption": "Overexpression of IRE1α K481R induced apoptosis. MEFs were transfected with indicated vectors. After 24 hours, these cells were stained with Annexin V-FITC",
    "ncbi_link": "IRE1α: 2081"
  },
  {
    "caption": "Overexpression of IRE1α K481R induced apoptosis. or subjected by immunoblotting with indicated antibodies (D).",
    "ncbi_link": "IRE1α: 2081"
  },
  {
    "caption": "Enhanced RIDD activity in IRE1α K481R. MEFs were transfected with indicated vectors 24 hours prior to analysis (E, F). The RIDD activity was measured by qRT-PCR.",
    "ncbi_link": "IRE1α: 2081"
  },
  {
    "caption": "Hyper-oligomerization of IRE1α K481R. MEFs were transfected with IRE1α-GFP or IRE1α K481R-GFP. After 24 hours, these cells were exposed with Tu for indicated periods and GFP signals were observed. The right panels show 5.5-fold magnification images of the boxed regions. Percentages of cells with IRE1α-foci were calculated from 100 cells by visual inspection in each independent experiment.",
    "ncbi_link": "GFP: 
IRE1α: 2081"
  },
  {
    "caption": "IRE1α regulation by MITOL occurred in the MAM-rich mitochondrial fraction. Crude mitochondrial fraction containing MAM (Mito plus MAM) and the cytosolic fraction containing ER (Cyto plus ER) were isolated from HEK293 cells transfected with indicated vector and subsequently immunoprecipitation assay was performed to detect the level of IRE1α ubiquitylation (D).",
    "ncbi_link": "MITOL: 54708"
  },
  {
    "caption": "Knockdown of PACS2 impaired the interaction of MITOL with IRE1α. HEK293 cells were transfected with either scramble RNA or siPACS2 and indicated vectors for 24 hours prior to immunoprecipitation assay.",
    "ncbi_link": "PACS2: 23241"
  },
  {
    "caption": "Knockdown of PACS2 inhibited IRE1α ubiquitylation by MITOL. HEK293 cells were transfected with either scramble RNA, siPACS2 and indicated vectors 24 hours prior to immunoprecipitation assay.",
    "ncbi_link": "PACS2: 23241"
  },
  {
    "caption": "Knockdown of Mfn2 inhibited IRE1α ubiquitylation by MITOL. HEK293 cells were transfected with either scramble RNA, siMfn2 and indicated vectors 24 hours prior to immunoprecipitation assay.",
    "ncbi_link": "Mfn2: 9927"
  },
  {
    "caption": "MITOL ubiquitylated IRE1α in the spinal cord of mice. Lysates of the spinal cord in mice were immunoprecipitated with anti-IRE1α antibody, followed by immunoblotting with indicated antibodies. WT: MITOLF/F mice, MITOLnestin: MITOLF/F, Nestin-Cre mice.",
    "ncbi_link": "Cre: 2777477
MITOL: 69104"
  },
  {
    "caption": "Loss of MITOL led to hyper-oligomerization of IRE1α in the spinal cord under ER stress. 3 month-old WT or MITOLnestin mice were treated with 1 mg/kg Tu for 24 hours. Spinal cord was solubilized with NP-40 lysis buffer and separated by sucrose-density gradient centrifugation.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "MITOL deletion resulted in hyper-activation of IRE1α RNase in ER stress. WT or MITOLnestin mice were injected with Tu for 24 hours and spinal cord was analyzed by qRT-PCR.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "Increased ER stress-induced apoptosis in the MITOL-KO spinal cord. 3 month-old WT or MITOLnestin mice were treated with Tu for 24 hours and each spinal cord was stained using TUNEL and hoechst (F) Arrowheads indicate the representative neurons.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "Increased ER stress-induced apoptosis in the MITOL-KO spinal cord. 3 month-old WT or MITOLnestin mice were treated with Tu for 24 hours and each spinal cord was stained using cresyl violet (G). Arrowheads indicate the representative neurons.",
    "ncbi_link": "MITOL: 69104"
  },
  {
    "caption": "(A) Cells in early G1 stably expressing nAC-mCherry and doxycycline-inducible ACTN4-SNAP were analyzed by time-lapse microscopy. ACTN4-SNAP was labeled by SNAP-Cell 647SiR dye (green). Different arrows mark dynamic ACTN4 clusters. The white square 1 is shown as a timeseries on the right. The white square 2 is shown as a magnification below. The white square 3 shows an actin filament decorated with ACTN4 that was analyzed by linescan in Fig 2B. Scale bar overview (nAC) represents 10 µm. Scale bar time series and magnification 5 µm.",
    "ncbi_link": "SNAP: 
ACTN4: 81"
  },
  {
    "caption": " Cells in early G1 stably expressing nAC-mCherry and doxycycline-inducible ACTN4-SNAP were analyzed by time-lapse microscopy. ACTN4-SNAP was labeled by SNAP-Cell 647SiR dye (green). The white square 3 shows an actin filament decorated with ACTN4 that was analyzed by linescan in Fig 2B. B) Linescan of an actin filament with associated ACTN4 from square 3 in A. ",
    "ncbi_link": "SNAP: 
ACTN4: 81"
  },
  {
    "caption": "(B) NIH3T3 cells stably expressing H2B-mCherry were transfected with siCtrl or siACTN1 + siACTN4. After mitotic exit z-stacks (30 planes) were acquired every 5 min. Nuclei were 3D-reconstructed and volume was measured by Imaris. Data are mean ± SEM from 3 biological replicates with 22-27 (siCtrl) and 32-42 (siACTN1+4) analyzed nuclei; ***p < 0.001 by Wilcoxon test and ****p < 0.0001 by t-test at 90 min.",
    "ncbi_link": "ACTN1: 109711
ACTN4: 60595
H2B: 68024"
  },
  {
    "caption": "(C) RPE-1 cells were analyzed as in B. Data are mean ± SEM from 5 biological replicates with 32-37 (siCtrl) and 31-39 (siACTN1+4) analyzed nuclei; ***p < 0.001 by Wilcoxon test and ****p < 0.0001 by Mann Whitney test at 90 min.",
    "ncbi_link": "ACTN1: 87"
  },
  {
    "caption": "(E) NIH3T3 cells stably expressing H2B-mCherry and siRNA-resistant ACTN4-NES were transfected with the indicated siRNAs and analyzed as described in B. Data are mean ± SEM from 5 biological replicates with 63-71 (siCtrl), 37-41 (siACTN1+4), 52-58 (siACTN1) and 52-55 (siACTN4) analyzed nuclei; ****p(siACTN4) < 0.0001; ****p(siACTN1+4) < 0.0001 by One Way ANOVA at 90 min.",
    "ncbi_link": "ACTN1: 109711
ACTN4: 81
ACTN4: 60595
H2B: 68024"
  },
  {
    "caption": "(F) NIH3T3 cells stably expressing H2B-mCherry and the indicated ACTN4 mutants were transfected with the indicated siRNAs and analyzed as in B. Data are mean ± SEM from 3 biological replicates with 63-69 (ACTN4 wt + siACTN4), 63-71 (ACTN4-NES + siCtrl) and 54-58 (ACTN4-NES + siACTN4) analyzed nuclei; ****p(ACTN4-NES + siACTN4) < 0.0001 by One Way ANOVA at 90 min.",
    "ncbi_link": "ACTN4: 60595
ACTN4: 81
H2B: 68024"
  },
  {
    "caption": "(G) NIH3T3 cells expressing siRNA-resistant ACTN4-NES were transfected with siCtrl or siACTN4; chromatin density was calculated from H2B-mCherry fluorescence intensities by total nuclear volumes (intensity/μm3) and normalized to t=0 (mitotic exit); Data are mean ± SEM from 5 biological replicates with 44-48 (siCtrl) and 44-47 (siACTN4) analyzed nuclei; ***p < 0.001 by Wilcoxon test and *p < 0.05 by t-test at 90 min.",
    "ncbi_link": "ACTN4: 81
H2B: 68024"
  },
  {
    "caption": "(B) Upper panel shows expression of ACTN4 constructs (green, confocal image) and phalloidin-AF647 staining in the same cells (orange, dSTORM image) scale bar 10 µm; lower panel represents zoom of the indicated areas (white boxes); scale bars 5 µm.",
    "ncbi_link": "ACTN4: 60595"
  },
  {
    "caption": "(C) Phalloidin-AF647 localizations per post-mitotic nuclei; data shown as mean ± 2.5-97.5 percentile: 52 ACTN4-wt nuclei, 55 ACTN4ΔCH1-NLS nuclei and 40 nuclei of non-dividing cells (ACTN4-wt) from 5 biological replicates. ***p(ACTN4ΔCH1-NLS post-mitotic) < 0.001, ****p(ACTN4-wt non-dividing) < 0.0001, *p (ACTN4ΔCH1-NLS post-mitotic vs. ACTN4-wt non-dividing) < 0.05 by One Way ANOVA.",
    "ncbi_link": "ACTN4: 60595"
  },
  {
    "caption": "(D) Number of filaments in the post mitotic nuclei; as in (C); data shown as mean ± 2.5-97.5 percentile: 52 ACTN4-wt nuclei, 55 ACTN4ΔCH1-NLS nuclei from 5 biological replicates, ***p < 0.001 by t-test.",
    "ncbi_link": "ACTN4: 60595"
  },
  {
    "caption": " (E) Actin filament widths for ACTN4-wt and ACTN4ΔCH1-NLS in early G1 nuclei; ); data shown as mean ± 2.5-97.5 percentile with 96 filaments (ACTN4-wt) and 36 filaments (ACTN4ΔCH1-NLS) from 5 biological replicates, **p < 0.01 by t-test. ",
    "ncbi_link": "ACTN4: 60595"
  },
  {
    "caption": "RT-qPCR analysis of METTL3 and METTL14 expression (A) in shRNA knockdown METTL3 cells.",
    "ncbi_link": "METTL14: 57721
METTL3: 56339"
  },
  {
    "caption": "I HA-METTL14 Co-IP with FLAG-tagged METTL3 domain-deletion mutants. β-actin was used as the loading control.",
    "ncbi_link": "FLAG: 
METTL3: 56339"
  },
  {
    "caption": "L Immunoblots showing CHX assay in HEK293T cells. Negative control (NC; no transfected cells) and STUB1-FLAG plasmid-transfected HEK293T cells were exposed to 100 μg/ml CHX for 0, 4, 8, or 12 hours. β-actin was used as the loading control. The METTL14/β-actin densitometric ratio was recorded by ImageJ.",
    "ncbi_link": "FLAG: 
STUB1: 10273"
  },
  {
    "caption": "M, N Dot blot assays showing that enforced expression of wild-type STUB1, but not the STUB1H260Q mutant, significantly decreases total m6A levels.",
    "ncbi_link": "STUB1: 10273"
  },
  {
    "caption": "B Immunoblots showing the abundance of METTL14 truncated mutants with or without 10 µM MG132 treatment. Histone H4 was used as the loading control. The HA-METTL14/β-actin densitometric ratio was recorded by ImageJ.",
    "ncbi_link": "METTL14: 57721"
  },
  {
    "caption": "F Immunoblots showing the levels of METTL14 protein after transfection with METTL14-3KR mutant plasmids with or without 10 µM MG132. β-actin was used as the loading control. The HA-METTL14/β-actin densitometric ratio was recorded by ImageJ. G Immunoblots showing the protein level of METTL14 after transfection with METTL14-3KR mutant plasmids under STUB1 knockdown. β-actin was used as the loading control. The HA-METTL14/β-actin densitometric ratio was recorded by ImageJ.",
    "ncbi_link": "METTL14: 57721
STUB1: 10273"
  },
  {
    "caption": "B METTL14 ubiquitination, as detected by IP of METTL3 truncated mutants with anti-HA antibody. The accumulation of Ub and METTL14 was confirmed in whole-cell lysates. β-actin was used as the loading control.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "C Immunoblots showing METTL14 protein levels, as detected by IP in response to METTL3 truncated mutants and STUB1-FLAG. β-actin was used as the loading control.",
    "ncbi_link": "FLAG: 
METTL3: 56339
STUB1: 10273"
  },
  {
    "caption": "E-G Following the subcutaneous inoculation of SK-Cha-1-NC (left) and SK-Cha-1-STUB1-FLAG (right) cells into the flanks of male NOD-SCID mice (E), overexpression of STUB1-FLAG inhibited malignant cell proliferation (F) and reduced subsequent tumor size and growth (G) in vivo. Data are means ± SEM. Statistical significance was analyzed by two-way ANOVA (F) or two-tailed unpaired t-test (G) (Five mice, *p < 0.05; **p < 0.01). H-J Following the subcutaneous inoculation of SK-Cha-1-sh-NC (left) and SK-Cha-1-sh-STUB1-1 (right) cells into the flanks of male nude mice (H), STUB1 knockdown promoted malignant cell proliferation (I) and increased subsequent tumor size and growth (J). Data are means ± SEM. Statistical significance was analyzed by two-way ANOVA (I) or two-tailed unpaired t-test (J). (Six mice, *p < 0.05; **p < 0.01; ***p < 0.001).",
    "ncbi_link": "FLAG: 
STUB1: 10273"
  },
  {
    "caption": "Immunoblots (K) showing METTL14 protein levels STUB1-FLAG overexpression in five pairs of mouse tumors. β-actin was used as the loading control. The METTL14 or STUB1-FLAG /β-actin densitometric ratio was recorded by ImageJ.",
    "ncbi_link": "FLAG: 
STUB1: 10273"
  },
  {
    "caption": "(b) RNAscope analysis of Lgr5 mRNA in DSS colitis demonstrating loss of Lgr5 transcript (N=3 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50µm",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "(d-e) Compared to untreated controls, DSS treatment ablates Lgr5-GFP+ stem cells and results in functional loss of tdTomato+ lineage tracing as early as d5. Lgr5-GFP+ stem cells reappear by d12 (N=3-4 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50µm Data are represented as mean ± SD (e) analyzed using Student's t-test. *P≤0.05, ** P≤0.01.",
    "ncbi_link": "GFP: 
tdTomato: 
Lgr5: 14160"
  },
  {
    "caption": "(f) Effects of DSS colitis injury on RNA expression levels of stem (Lgr5 and Krt19) and progenitor (Atoh1 and Notch1) cell markers. Lgr5 mRNA expression is significantly decreased after exposure to DSS (N=6-7 per condition). Data are represented as mean ± SEM analyzed using Student's t-test. *P≤0.05, ** P≤0.01.",
    "ncbi_link": "Atoh1: 11921
Krt19: 16669
Lgr5: 14160
Notch1: 18128"
  },
  {
    "caption": "(k) The extent of epithelial damage is similar in mice treated with DSS alone versus DSS+DT (to ablate Lgr5+ stem cells) (N=3 DSS; N=6 DSS+DT). Data are represented as mean ± SEM analyzed using Student's t-test. *P≤0.05, ** P≤0.01.",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "(l) RNAscope for Lgr5 in Lgr5DTR-GFP mice showing loss of Lgr5 transcripts after DT treatment (N=3-4 per condition). Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars =50µm",
    "ncbi_link": "GFP: 
DTR: 15200
Lgr5: 14160"
  },
  {
    "caption": "DT ablation of Krt19+ cells significantly reduced the number of lineage labeled crypts (N≥3 per condition). Data are represented as mean ± SEM using Student's t-test *P≤0.05, **P≤0.01.",
    "ncbi_link": "Krt19: 16669"
  },
  {
    "caption": "Images of tissue sections Notch1CreERT2; ROSA26tdTomato;Lgr5DTR-GFP mice (f) showing Notch1 lineage labeled crypts. No partially labeled crypts were found after Lgr5+ stem cell ablation. Data information: Nuclei are counterstained with Dapi (blue); white dashed lines indicate basement membrane. Scale bars=50μm.",
    "ncbi_link": "GFP: 
Cre: 2777477
ROSA26: 14910
DTR: 15200
Lgr5: 14160
ERT2: 26417
Notch1: 18128"
  },
  {
    "caption": "(d-e) Flow cytometry for tdTomato+ cells in crypt epithelium from DT treated Atoh1CreERT2;Lgr5DTR-GFP;ROSA26tdTomato mice.",
    "ncbi_link": "GFP: 
tdTomato: 
Atoh1: 11921
Cre: 2777477
ROSA26: 14910
DTR: 15200
Lgr5: 14160
ERT2: 26417"
  },
  {
    "caption": "(f) tdTomato+ colonic organoids from single Atoh1-tdTomato+/Lgr5-negative cells (N=1; n=3 technical replicates per condition). Data information: Scale bars =100μm",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "(h) tdTomato+ colonic organoids established from mice in which Lgr5+ stem cells have been ablated show higher growth efficiency compared to their colonic organoid counterparts (N=1; n=3 technical replicates per condition). Data are represented as mean ± SD analyzed using two-way ANOVA with Sidak's multiple comparisons test (h). *P≤0.05, **P≤0.01, ***P≤0.001.",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "C: The infectivity  of PIPLC  and PK-treated cell lysates was determined by infecting CAD5  cells with lysates as indicated. The signal intensity of the highest dilution was measured and compared to untreated RML CAD5  cell lysate. PIPLC-treated cells and PK-treated lysates showed similar infectivity  titers. Prion-infected and NBH, as well as RML on CAD5ΔPrnp were used for control.",
    "ncbi_link": "Prnp: 19122"
  },
  {
    "caption": "D: RML-infected CAD5  and GT-1/7  cells were transfected with non-targeting (NT) or Prnp  targeting siRNAs in a 384-well plate and subjected to PK    or PIPLC   treatment. Z'-factors were calculated for each condition. Shown are mean ± SD, n = 22 individually cultured wells.",
    "ncbi_link": "Prnp: 19122"
  },
  {
    "caption": "A: Western blot showing Hnrnpk siRNA transfection (96 hrs.) decreases Hnrnpk protein levels while increases PrPSc in RML prion infected GT-1/7. Prnp siRNAs suppressed both PrPC and PrPSc as expected. ⍺: anti Quantifications are reported as normalized to Actin and in comparison, to NT. PK-western blot is quantified relative to NT.",
    "ncbi_link": "Hnrnpk: 15387
Prnp: 19122"
  },
  {
    "caption": "C: mRNA levels of Hnrnpk  and Prnp  following siRNA and PSA  treatment. FPKM: Fragments per kilobase of transcript per million mapped reads. Hnrnpk  siRNAs lead to a decrease in Hnrnpk  mRNA levels as well as an increase in Prnp  mRNA levels. No difference is seen between DMSO  treated and PSA  treated cells for either Hnrnpk  levels of Prnp  levels. n = 2 per treatment group.",
    "ncbi_link": "Hnrnpk: 15387
Prnp: 19122"
  },
  {
    "caption": "E: Brightfield microscopy  images of the effect of siRNA mediated HNRNPK  downregulation on prion-induced vacuolation  in PG127 hovS   cells. Downregulation of HNRNPK  leads to an enhanced cytopathological vacuolation  phenotype when compared to NT siRNA. ovPRNP siRNA transfected, as well as uninfected cells were used as controls Downregulation of ovPRNP in the infected hovS   eliminates the vacuoles; Right panel: Quantification of vacuoles  of NT, HNRNPK  and ovPRNP siRNA treated PG127  hovS. Cells from pictures at three different positions in the well were manually counted and the amount of vacuolated cells was normalized to the total amount of cells. Values represent mean ± SD. * p = 0.0113, **** p = <0.0001 (Dunnett's multiple comparisons test). Scale bar = 100 µm. n = 3 technical replicates.",
    "ncbi_link": "HNRNPK: 3190
PRNP: 493887"
  },
  {
    "caption": "G: Same as in E, using shRNAs instead of siRNA. Downregulation of HNRNPK  leads to an enhanced cytopathological vacuolation  phenotype when compared to NT shRNA. Uninfected cells were used as controls Right panel: Quantification of vacuoles  of NT and HNRNPK  shRNA treated PG127 hovS. Cells from pictures at three different positions in the well were manually counted and the amount of vacuolated cells was normalized to the total amount of cells. Values represent mean ± SD. *** p = <0.0009 (Dunnett's multiple comparisons test). Scale bar = 100 µm. n = 3 technical replicates.",
    "ncbi_link": "HNRNPK: 3190"
  },
  {
    "caption": "H: Quantification of PrPSc  levels in PG127 hovS  cells following treatment with shRNA against HNRNPK  and 1 µM PSA  in comparison to DMSO  and NT. Each dot represents an experiment. *= p-value < 0.027 (Student's t-test). Shown are mean ± SD.",
    "ncbi_link": "HNRNPK: 3190"
  },
  {
    "caption": "I: Gene set overrepresentation analysis of differentially expressed genes (log2FC -0.25 ≥ or 0.25 ≤ and FDR ≤ 0.05) for siRNA mediated Hnrnpk  downregulation or PSA  treatment in RML GT-1/7 cells analyzed by  RNAseq. Differentially regulated genes (up in siRNA treatment and down in PSA  or vice versa) were overlapped and used for pathway analysis. No significantly enriched pathways are detected for upregulated genes in Hnrnpk  and downregulated in PSA  treatment. For the opposing direction, an enrichment of genes involved in glucose  metabolism was detected.",
    "ncbi_link": "Hnrnpk: 15387"
  },
  {
    "caption": "(F) Stills from time-lapse  sequence of representative  Hela cells expressing  mNeon-Green Aurora B  and Cell Mask to label cell membrane, exiting mitosis, showing the dynamic  re-localization of Aurora B  from DNA  to the overlapping  microtubules and cleavage furrow with control siRNA treatment (arrows top). With knock-down of RACGAP1, Aurora B still re-localises from the DNA to the microtubules and furrow  in the midzone in early anaphase (arrows bottom), but the microtubule localization is lost at later stages (asterisk bottom). Scale bar - 10 µm.",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "(E) Stills of representative Hela  cells expressing  Lifeact-GFP and  H2B-mCherry   at 10 mins following forced mitotic exit with siControl, siRACGAP1, DMSO  and 2µM ZM447439 treatment. Control siRNA, RACGAP1  siRNA and DMSO  treated cells show clearance  of  actin from the cortex  close to the DNA, while ZM447439 treated cells fail to clear  actin, quantified in (F). Note, failure in  actin  accumulation in RACGAP1 depleted cell, asterisk. Scale bar - 10 µm",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "(F) Quantification of  actin    intensity across the perimeter  of the cells based on distance from DNA, with 5 and 6 being closest to DNA and 1 and 10 furthest away, as in cartoon (B). Graph shows decrease in  actin intensity closer to the DNA in siControl (n=26), siRACGAP1 (n=37) and Control DMSO  treated cells (n=38 cells), seen by levels lower than 1 (dotted red line), while this decrease is absent in  ZM447439 treated cells (n=42 cells). Data presented as mean ± SD.",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "(D) Still images of representative  Hela  cells expressing Lifeact-GFP and H2B-mCherry captured at early anaphase  under different conditions i.e. Control siRNA, knock-down of centralspindlin  protein RACGAP1, in the presence and absence of  Aurora B kinase inhibitor (2µM ZM). Scale bar - 10 µm (E) Quantification of aspect ratio of cells treated with different conditions as in (D) at 6 mins after anaphase onset, before furrow formation. Aurora B inhibition and siRACGAP1 individually have a moderate effect on aspect ratio, while together have a stronger impact during mitotic exit. In combined treatment, mitotic cells hardly undergo any elongation and remain spherical before re-spreading. Ordinary one-way ANOVA with multiple comparison. Each treatment is compared with siControl, ****p<0.0001 for all comparisons. Data represented as box-whisker plot, with box showing 25th-75th percentile values, whiskers-min to max value and line representing median. Mean±SD for different treatments- siControl (n=38) - 1.455±0.19, ZM  (n=32) - 1.219±0.16, siRACGAP1  (n=25) -1.144±0.078 and siRACGAP1+ZM (n=16) - 1.013±0.03. Cells for different treatment pooled from n>3 independent experiments. ",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "(C) Quantification of actin  intensity at the poles of cells at 6 mins post anaphase onset, before furrow  formation under different conditions as in (A). Actin fails to be cleared from the poles upon Aurora B kinase inhibition during mitotic exit and is stronger when both centralspindlin  and Aurora B kinase  activity are affected, while it is cleared upon RACGAP1 depletion. Data represented as mean±SD for treatments - siControl- 0.98±0.05, siRACGAP1  - 0.99±0.04, ZM - 1±0.039, siRACGAP1+ZM - 1±0.037. Ordinary one-way ANOVA with multiple comparison- siControl vs siRACGAP1 - n.s., p=0.896, siControl vs  ZM - **p=0.0018, siControl vs siRACGAP1+ZM - ****p<0.0001 and ZM  vs siRACGAP1+ZM - p=0.1528.",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "(G) Quantification of shortest distance between centroid of DNA and cortical actomyosin  network. While chromatin is able to reach close to the cortex in both siControl and siRACGAP1  treated cells, the distance of chromatin  from cortex  increases upon  ZM treatment and is further enhanced in the double treatment condition. Data represented as mean±SD. siControl - 4.7±0.87, siRACGAP1 - 4.4±0.64,  ZM - 5.47±0.87, siRACGAP1+ZM - 6.35±1.14 microns. Ordinary one-way ANOVA with multiple comparison, siControl vs ZM, ***p=0.002, siControl vs siRACGAP1, p=0.2823, siControl vs siRACGAP1+ZM, ****p<0.0001, siRACGAP1 vs siRACGAP1+ZM, ****p <0.0001, ZM  vs siRACGAP1, ****p<0.0001, ZM  vs siRACGAP1+ZM, ***p=0.0004 .",
    "ncbi_link": "RACGAP1: 29127"
  },
  {
    "caption": "HeLa CCL2 cells stably expressing control vector only (+vector), β-catenin WT (+WTR), S60A mutant (+S60AR), or S60D mutant (+S60DR) were generated using lentiviral infection and then infected with β-catenin knockdown lentivirus (shβ-catenin). A dot density graph with a box plot shows the percentage (%) of cells with cytokinesis-defective phenotypes (C). The box plot represents: central blue band, Median; box, Interquartile range; upper whisker, Maximum observation below upper fence; lower whisker, Minimum observation above lower fence; dot, Outlier. Each symbol in the graph represents a percentage of more than 30 cells from three independent experiments. ***, p<0.001 (one-way ANOVA); Scale bars, 10 μm.",
    "ncbi_link": "β-catenin: 12387"
  },
  {
    "caption": "HeLa CCL2 cells transiently transfected with either GFP-β-catenin WT or GFP-β-catenin S60A were monitored during cell cycle progression by live cell imaging (E). The subcellular localizations of GFP-tagged β-catenin WT or S60A mutant construct were confirmed by immunofluorescence with anti-GFP antibody. The cells were additionally stained for Plk1 (see Appendix Figure S5A). The specific localization of GFP-β-catenin WT at the midbody was observed under a confocal laser microscope with high magnification (E, left panel). Cytokinesis-defective cellular phenotypes in each transfected HeLa cell were monitored (E, right panel)",
    "ncbi_link": "GFP: 
β-catenin: 12387"
  },
  {
    "caption": "(G, H) HeLa CCl2 cells infected with either sh-control luciferase (shGL) or shβ-catenin lentiviruses were co-immunostained with anti-β-catenin and anti-Ect2 antibodies. Localization of β-catenin and Ect2 in the midbody of telophase cells was observed using a confocal microscope (G) and the signal intensity of Ect2 was monitored in the midbody of each knockdown telophase cell (H). Arrows indicate total β-catenin and Ect2 located at the midbody in telophase HeLa CCL2 cells (G). A dot density graph with a box plot shows the signal intensity of midbody-localized Ect2 in telophase cells. The box plot represents: central blue band, Median; box, Interquartile range; upper whisker, Maximum observation below upper fence; lower whisker, Minimum observation above lower fence; dot, Outlier. Approximately 70 cells from three independent experiments were measured. ***, p<0.001 (unpaired two-tailed t test); Scale bars, 10 μm. The value of the relative neck thickness is shown in the lower left corner of the merged images (G).",
    "ncbi_link": "luciferase: 
β-catenin: 12387"
  },
  {
    "caption": "(G) HeLa CCL2 cells were transfected with either wild type Flag−β-catenin (+WT), Flag-β-catenin S60A mutant (+S60A), or Flag-β-catenin S60D mutant (+S60D), then treated with 200 ng/mL nocodazole for 18 h (metaphase) and released by incubation in fresh medium for 2 h (telophase). Cell lysates were used for pull-down analysis with rhotekin-RBD beads, and the pulled down beads were separated by 12 % SDS-PAGE followed by immunoblot analysis with the indicated antibodies. The membrane was then stained with Coomassie (CBB) to determine the amount of RBD precipitated.",
    "ncbi_link": "Flag: 
β-catenin: 12387"
  },
  {
    "caption": "(A) 786-0 or 769-P cells stably expressing shNT or shGDH1  were treated with or without aa starvation for the indicated  times, and then  cell viability was assessed. (B) 786-0  or 769-P  cells stably expressing shNT or shGDH1  were reconstituted with or without various amounts of rGDH1 WT (3*WT indicates 3-fold expression WT) and then treated with aa  starvation for the indicated  time. Cell viability  was subsequently assessed. ( Data information: The data are represented as means ± SEM of three independent experiments and all statistical analyses were conducted using unpaired t-test. (**p < 0.01; ***p < 0.001.)",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(G) Immunofluorescence (IF) assay was performed to determine the subcellular location of WT or   mitochondrial  signal peptide deleted  (dMSP) GDH1. GDH1 localization was indicated by GDH1 antibody and MitoTracker  (left). Signal intensities and distances were quantified (right). Scale bars: 20 μm.",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(H) Cytoplasm-mitochondrial fractionation assay  was performed to determine the subcellular location of WT or   mitochondrial signal peptide deleted (dMSP) GDH1. The fractionation efficiency  and GDH1 location were determined by WB using antibodies against  VDAC1 (mitochondrial membrane marker) and  GDH1. Tubulin was used as loading control.",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(D) FLAG-tagged GDH1 (including WT and mutants with different  lysine mutations to  arginine) was co-transfected with  HA-tagged ubiquitin for 48 hours, and then cells were subjected to  aa  starvation for 12 hours before collecting cells.  WB and qPCR separately tested the levels of GDH1  protein and mRNA, respectively. Data information: The data are represented as the mean ± SEM of three independent experiments. The one-way ANOVA test (N.S.: not significant; *p < 0.05; **p < 0.01; ***p < 0.001).",
    "ncbi_link": "FLAG: 
HA: 
GDH1: 2746
ubiquitin: 7323///7321///7322"
  },
  {
    "caption": "(H) 786-0 or 769-P cells stably expressing shGDH1  were reconstituted with rGDH1 WT or 3KR mutant and then treated with or without aa starvation for the indicated time. Cell viability was determined. Unpaired two-tailed t-test was used. Data information: The data are represented as the mean ± SEM of three independent experiments. The unpaired t-test were used (N.S.: not significant; *p < 0.05; **p < 0.01; ***p < 0.001).",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(H) 786-0  or 769-P cells (WT or stably expressing shGDH1) were transfected with siNC or siRNF213 for 48 hours and then were treated with or without aa starvation for the indicated times. Cell viability  was determined. Unpaired t-test was used with ***p < 0.001.",
    "ncbi_link": "GDH1: 2746
RNF213: 57674"
  },
  {
    "caption": "786-0  cells expressing WT or enzymatically dead (ED) GDH1 were transfected with siNC or siRNF213 for 48 hours and then were treated with or without aa starvation for 12 hours. In the above cells in (A), qPCR was used to measure the mRNA of the indicated RP genes (C).",
    "ncbi_link": "GDH1: 2746
RNF213: 57674"
  },
  {
    "caption": "Xenogeneic inoculation of 786-0  cells lacking  GDH1 with restored expression of WT, ED or 3KR mutant GDH1 into the left groin of nude mice. The solid tumor formed by the indicated 786-0  cells is shown (B).",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "Xenogeneic inoculation of 786-0  cells lacking GDH1 with restored expression of WT, ED or 3KR mutant GDH1 into the left groin of nude  mice. The staining of  Ki67 (G, upper panel) and TUNEL  (G, lower panel) using tumors from (B) are shown and analyzed (G, right panel). We used 6  mice in each group. Scale bars: 50 μm. Data information: All statistical analyses were conducted using unpaired t-test (n = 6). (N.S.: not significant; *p < 0.05; **p < 0.01; ***p < 0.001).",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(A) WT, Irgm1-/-, Irgm2-/- and Irgm3-/- mice (n = 4 mice/genotype) were injected i.p. with LPS (8 mg/kg). Serum was collected 4 hours post injection (hpi) and concentration of various cytokines determined via a preconfigured Luminex multiplex panel. Relative concentration (fold change relative mean of WT) is shown for the indicated cytokines (absolute cytokine concentrations of same experiment are shown in Fig EV1).",
    "ncbi_link": "Irgm3: 16145
Irgm1: 15944
Irgm2: 54396"
  },
  {
    "caption": "(B) WT (n = 9), Irgm1-/- (n = 7), Irgm2-/- (n = 9) and Casp1-/-Casp11-/- (n = 7) mice were injected i.p. with LPS (8 mg/kg). Serum was collected 4 hpi and concentration of IL-1β, IL-18, and TNFα was measured via ELISA.",
    "ncbi_link": "Casp1: 12362
Casp11: 12363
Irgm1: 15944
Irgm2: 54396"
  },
  {
    "caption": "(A) qPCR measurement of IL-1β, and TNF-α mRNA levels in WT and Irgm2-/- BMMs following 8-hour stimulation with LPS (1 µg/ml).",
    "ncbi_link": "IL-1β: 16176
Irgm2: 54396
TNF-α: 21926"
  },
  {
    "caption": "(B) WT, Irgm2-/- and Casp1-/-Casp11-/- BMMs were treated for 24 hours with LPS at indicated doses and supernatant TNFα, IL-1β, and IL-18 was measured by ELISA.",
    "ncbi_link": "Casp1: 12362
Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(C) IFNγ-primed WT and Irgm2-/- BMMs were treated with LPS, Pam3CSK4, poly(I:C) or a combination of Pam3CSK4 and poly(I:C) (1 µg/ml for all treatments) for 24 hours and cell supernatant IL-1β and IL-18 concentrations were assessed by ELISA.",
    "ncbi_link": "Irgm2: 54396"
  },
  {
    "caption": "(D) WT, Irgm2-/-, Casp1-/-Casp11-/- and Irgm2-/-Casp1-/-Casp11-/- BMMs were treated with LPS (1 µg/ml) and IL-1β, IL-18, and LDH release were assessed at 24 hours post treatment (hpt).",
    "ncbi_link": "Casp1: 12362
Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(E) IFNγ-primed WT, Irgm2-/-, Casp1-/-Casp11-/- and Irgm2-/-Casp1-/-Casp11-/- BMMs were treated with LPS (5 µg/ml) for 4 hours and subsequently stained with anti-ASC antibody and Hoechst stain (DNA/nuclei). Representative images are shown with white arrows pointing at ASC specks. Number of ASC specks per nuclei was quantified. Scale bars: 20 µm.",
    "ncbi_link": "Casp1: 12362
Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(F) IFNγ-primed WT, Irgm2-/-, Casp1-/-Casp11-/- and Irgm2-/-Casp1-/-Casp11-/- BMMs were treated with LPS (1 µg/ml) for 24 h and cell lysates and supernatants collected. Protein levels in cell lysates (caspase-1, and actin) and supernatants (caspase-1 p20) were visualized via immunoblotting.",
    "ncbi_link": "Casp1: 12362
Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(A) IFNγ primed WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were treated with LPS (5 µg/ml) for 4 h. Following treatment, cells were stained with anti-ASC antibody and Hoechst (DNA/nuclei). Representative images of ASC specks (white arrows point at specks) are shown and number of ASC specks per nuclei quantified. Scale bars: 20 µm.",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(B) WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were treated with LPS (1 µg/ml). IL-1β, IL-18, and LDH release were assessed at 24 hours-post treatment (hpt).",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (C) WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were infected with E. coli K-12 at indicated MOIs and cell viability assessed via CellTiter-Glo. Cell death was calculated as a function of relative viability to uninfected cells. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (D) WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were infected with E. coli K-12 (MOI 25) and 24 hpi supernatant IL-1β and IL-18 levels were measured by ELISA. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (E) WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were treated with OMVs at indicated concentrations for 24 h. Cell viability was assessed via CellTiter-Glo and cell death was calculated as a function of relative viability to untreated cells. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (F) WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were treated with OMVs (1 µg/ml) and 24 hpt cell supernatant IL-1β and IL-18 levels were measured via ELISA. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (A) WT, and Irgm2-/- BMMs were stimulated overnight with IFNγ or left untreated and cell lysates were collected. Lysates were assessed for Casp11, Gbp2, and actin protein levels via immunoblotting. ",
    "ncbi_link": "Irgm2: 54396"
  },
  {
    "caption": " (B) IFNγ-primed and unprimed WT, Irgm2-/-, Gbpchr3-/- and Aim2-/- BMMs were infected with Francisella novicida (MOI 10) and LDH release measured at 4 hpi. ",
    "ncbi_link": "Aim2: 383619
Gbp: 14468
Irgm2: 54396"
  },
  {
    "caption": " (C) WT, Irgm2-/-, Gbpchr3-/- and Irgm2-/- Gbpchr3-/- BMMs were treated with LPS (1 µg/ml). IL-1β, IL-18, and LDH release were assessed at 24 hpt. ",
    "ncbi_link": "Gbp: 14468
Irgm2: 54396"
  },
  {
    "caption": " (D) IFNγ-primed WT, Irgm2-/-, Gbpchr3-/- and Irgm2-/- Gbpchr3-/- BMMs were treated with LPS (1 µg/ml) for 24 hours and cell lysates and supernatants collected. Protein levels in cell lysates (Caspase-1, and actin) and supernatants (Caspase-1 p20) were visualized via immunoblotting. ",
    "ncbi_link": "Gbp: 14468
Irgm2: 54396"
  },
  {
    "caption": " (A) WT, Irgm2-/-, and Nlrp3-/- BMMs were treated with LPS (0.1 µg/ml) for 3 h followed by nigericin for 1 h and IL-1β/LDH release was measured. ",
    "ncbi_link": "Irgm2: 54396
Nlrp3: 216799"
  },
  {
    "caption": " (B) WT, Irgm2-/-, Casp11-/- and Irgm2-/-Casp11-/- BMMs were treated with LPS (0.1 µg/ml) for 3 h followed by nigericin and/or MCC950 for 1 h and IL-1β/LDH release was measured. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (C) WT, Irgm2-/-, Casp11-/- and Irgm2-/-Casp11-/- BMMs were treated with LPS (1 µg/ml) and/or MCC950 for 24 h and IL-1β/LDH release was measured. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (D) IFNγ-primed WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were transfected with LPS using lipofectamine LTX and LDH release was measured at 2 hpt. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (E) IFNγ-primed WT, Irgm2-/-, Casp11-/- and Irgm2-/- Casp11-/- BMMs were co-treated with LPS (indicated doses) and Listeria monocytogenes (MOI 10) and LDH release measured at 4 hpt. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (A) WT (n = 9), Irgm2-/- (n = 10), Casp11-/- (n = 7) and Irgm2-/-Casp11-/- (n = 8) mice were injected i.p. with LPS (8 mg/kg). Morbidity and mortality were observed for 48 h at 3 hour intervals. ",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (B) WT (n = 9), Irgm2-/- (n = 8), Casp11-/- (n = 7) and Irgm2-/-Casp11-/- (n = 10) mice were injected i.p. with LPS (8 mg/kg). Serum was collected 4 hpi and concentration of IL-1β, and IL-18 was measured by ELISA. Data shown are from 2 pooled experiments.",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": " (A) WT, Irgm2-/-, Irgm3-/-, Irgm2-/-Irgm3-/-, panIrgm-/-, and Casp11-/- BMMs were treated with LPS (1 µg/ml) or infected with E. coli K-12 (MOI 25) and IL-1β, and LDH release were assessed at 24 hpt (n = 3 independent experiments). (B) IFNγ-primed WT, Irgm2-/-, Irgm3-/-, Irgm2-/-Irgm3-/-, panIrgm-/-, and Casp11-/- BMMs were treated with LPS (1 µg/ml) or infected with E. coli K-12 (MOI 25) and IL-1β, and LDH release were assessed at 8 hpt/ hpi (n = 3 independent experiments). ",
    "ncbi_link": "Casp11: 12363
Irgm3: 16145
Irgm: 15944
Irgm2: 54396"
  },
  {
    "caption": " (C) WT (n = 15), Irgm2-/- (n = 12), and panIrgm-/- (n = 13) mice were injected i.p. with LPS (8 mg/kg). Serum was collected 4 hpi and concentration of IL-1β and TNFα was measured via ELISA. Data shown are from 3 pooled experiments. ",
    "ncbi_link": "Irgm: 15944
Irgm2: 54396"
  },
  {
    "caption": " (D) WT, Irgm2-/-, panIrgm-/- and Casp11-/- mice (n = 8 mice/genotype) were injected i.p. with LPS (8 mg/kg body weight). Morbidity and mortality were observed for 48 h at 3-h intervals. ",
    "ncbi_link": "Casp11: 12363
Irgm: 15944
Irgm2: 54396"
  },
  {
    "caption": "A,B Tumor growth curve (left) and summary of end-point tumor masses (right) of 6-8 week-old wildtype (WT) and Peli1-KO (KO) mice inoculated s.c. with B16F10 (A; WT, n=7; KO, n=6) or E.G7 (B; WT, n=5; KO, n=5) tumor cells.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "C,D Flow cytometry analysis of CD4+ and CD8+ T cells in CD45.2+ TILs and dLN cells from B16F10 tumor-bearing wildtype and Peli1-KO mice, presented as a representative plot (C) and summary graph based on multiple mice (D; WT, n=6; KO, n=6).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "E,F Flow cytometry analysis of IFNγ-producing CD4+ and CD8+ T cells in TILs, and dLN cells of B16F10 tumor-bearing (day 19) wildtype and Peli1-KO mice, presented as a representative plot (E) and summary graph (F). (WT, n=6; KO, n=6)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "G,H Flow cytometry analysis of IFNγ+CD8+ T cells in TILs of E.G7 tumor-bearing (day 24) wildtype and Peli1-KO mice, presented as a representative plot (G) and summary graph (H). (WT, n=3; KO, n=3)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "A,B Tumor growth curve (left) and summary graph of end-point tumor masses (right) of wildtype (WT) and Peli1-TKO (TKO) mice inoculated s.c. with B16-OVA (A; WT, n=5; KO, n=5) or E.G7 (B; WT, n=6; KO, n=4) tumor cells.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "C Flow cytometry analysis of IFNγ-producing CD4+ and CD8+ T cells in TILs and dLN cells from B16OVA tumor-bearing wildtype and Peli1-TKO mice, presented as a representative plot (upper) and summary graph (lower). (WT, n=5; KO, n=5)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "D Flow cytometry analysis of GZMB+CD8+ T cells in TILs from B16-OVA tumor-bearing wildtype and Peli1-TKO mice, presented as a representative plot (upper) and summary graph (lower). (WT, n=5; KO, n=5)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "E Tumor growth curve (left) and summary graph of end-point tumor masses (right) of B16-OVA tumor-bearing wildtype and the indicated Peli1 conditional KO mice. (Treg KO model: WT, n=5; Treg KO, n=6; MKO model: WT, n=3; MKO, n=5; BKO model: WT, n=9; BKO, n=9)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "A,B Seahorse analysis of basal (glucose injection) and maximal (oligomycin injection) ECAR or basal (no treatment) and maximal (FCCP injection) OCR in WT and Peli1-KO OT-I CD8 T cells that were either untreated (naïve) or activated with plate-bound anti-CD3 (1 μg/ml) plus anti-CD28 (1 μg/ml) for 16 h. Data are presented as a representative plot (A) or summary graph based on 6 wildtype and 6 KO mice (B).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "qRT-PCR analysis of the indicated genes using RNAs isolated from wildtype or Peli1-KO OT-I CD8 T cells stimulated with anti-CD3 and anti-CD28 for 6 h.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "D qRT-PCR analysis of the indicated genes using RNAs isolated from wildtype or Peli1-KO OT-I CD8 T cells stimulated with anti-CD3 and anti-CD28 for 6 h.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "E Immunoblot analysis of HK2 and Glut1 in wildtype or Peli1-KO OT-I CD8 T cells that were stimulated with plate-bound anti-CD3 and anti-CD28 for 24 h.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "A Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of freshly isolated CD8 T cells from wildtype (WT) or Peli1 KO (KO) mice (6 weeks old). Data are presented as a representative blot (left) and summary graphs of densitometric quantifications of the indicated proteins (presented as phosphorylated/total protein ratio) based on three independent experiments.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "B,C Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype or Peli1-KO OT-I CD8 T cells that were first rested on ice for 15 min and then stimulated in low-serum (1% FBS) medium with anti-CD3 and anti-CD28 for the indicated time periods.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "D,E Seahorse analysis of basal and maximal ECAR (D) or OCR (E) using wildtype or Peli1-KO OT-I CD8 T cells that were activated for 16 h with plate-bound anti-CD3 (1 μg/ml) plus anti-CD28 (1 μg/ml) in the presence of solvent control (DMSO), rapamycin (Rapa, 10 nM), or Torin 1 (100 nM). Data are presented as a representative plot (left) and summary graphs (right).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "F,G Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype or Peli1-KO OT-I CD8 T cells that were either not treated (-) or stimulated (+) for 1 h (F) or 24 h (G) with anti-CD3 (1 μg/ml) and anti-CD28 (1 μg/ml) in the presence (+) or absence (-) of rapamycin (10 nM) and Torin 1 (100 nM).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "H qRT-PCR analysis of Ifng gene expression in naïve wildtype or Peli1-KO OT-I CD8 T cells that were either not treated (-) or stimulated for 6 h (+) with anti-CD3 plus anti-CD28 in the presence (+) or absence (-) or rapamycin.",
    "ncbi_link": "Ifng: 15978
Peli1: 67245"
  },
  {
    "caption": "I-K Schematic of experimental design (I), tumor growth curve (J), and summary of day 15 tumor weight (K) of B6.SJL mice inoculated with B16-OVA melanoma cells (2 x 105) and adoptively transferred on day 7 with in vitro activated and rapamycin- or DMSO-treated wildtype or Peli1-KO OT-I CD8 T cells (4 x 105).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype (WT) or Peli1-KO (KO) OT-I CD8 T cells that were activated for 16 h with plate-coated anti-CD3 (1 μg/ml) plus anti-CD28, starved for 6 h in serum-free RPMI medium, and then treated for indicated time periods with FBS (10%) (A)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype (WT) or Peli1-KO (KO) OT-I CD8 T cells that were activated for 16 h with plate-coated anti-CD3 (1 μg/ml) plus anti-CD28, starved for 6 h in serum-free RPMI medium, and then treated for indicated time periods with insulin (B).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype (WT) or Peli1-KO (KO) MEFs that were starved for 16 h in serum-free DMEM medium and then treated for the indicated time periods with FBS (C)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype (WT) or Peli1-KO (KO) MEFs that were starved for 16 h in serum-free DMEM medium and then treated for the indicated time periods with insulin (D)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in whole-cell lysates of wildtype (WT) or Peli1-KO (KO) MEFs that were starved for 16 h in serum-free DMEM medium and then treated for the indicated time periods with EGF (E).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "A Immunoblot analysis of the indicated proteins in whole-cell lysates of wildtype (WT) and Peli1-KO (KO) CD8 T cells that were either not treated (NT) or activated for 16 h with plate-bound anti-CD3 and anti-CD28. Data are presented as a representative blot (left panel) and a summary graph of quantified TSC1 (middle panel) and TSC2 (right panel) protein bands relative to the level of α-Tubulin.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Immunoblot analysis of the indicated proteins in whole-cell lysates of wildtype and Peli1-KO CD8 T cells that were activated for 1 h with anti-CD3 and anti-CD28 and then treated with cycloheximide (CHX) for the indicated time periods. Data are presented as a representative blot (B)",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "D Immunoblot analysis of TSC1 and TSC2 in wildtype or Peli1-KO CD8 T cells stimulated with anti-CD3 plus anti-CD28 for 1 h and then incubated with (+) or without (-) cycloheximide (CHX) and/or MG132 for 2 h. Data are presented as a representative blot (left panel) and a summary graph of quantified TSC1 (middle panel) and TSC2 (right panel) protein bands relative to the level of α-Tubulin.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Ubiquitination analysis of immunoprecipitated TSC2 (E) from activated (anti-CD3 plus anti-CD28 for 2 h) wildtype or Peli1-KO CD8 T cells by immunobloting using anti-ubiquitin Abs detecting total (Ub), K48 (Ub-K48), or K63 (Ub-K63) polyubiquitin chains.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "Ubiquitination analysis of immunoprecipitated TSC1 (F) from activated (anti-CD3 plus anti-CD28 for 2 h) wildtype or Peli1-KO CD8 T cells by immunobloting using anti-ubiquitin Abs detecting total (Ub), K48 (Ub-K48), or K63 (Ub-K63) polyubiquitin chains.",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "L Co-immunoprecipitation analysis of endogenous TSC1-TSC2 interaction in wildtype and Peli1-KO CD8 T cells that were either not treated (NT) or stimulated for 2 h with anti-CD3 plus anti-CD28. The right panel is a summary graph of TSC2/TSC1 ratio based on quantification of the blot from anti-TSC1 IP (the right four lanes of the top two panels).",
    "ncbi_link": "Peli1: 67245"
  },
  {
    "caption": "A Analysis of ubiquitin conjugation to wildtype (WT) TSC1 and the indicated TSC1 mutants in 293T cells transiently transfected Flag-tagged TSC1 and its mutants along with (+) or without (-) the indicated expression vectors.",
    "ncbi_link": "Flag: 
TSC1: 7248"
  },
  {
    "caption": "B Immunoblot analysis of the indicated phosphorylated (p-) and total proteins in lysates of TSC1-KO MEFs transfected with (+) or without (-) TSC1 wildtype or K30A expression vectors. The cells were serum starved and then left either untreated (NT) or stimulated with 10% FBS for 30 mins. Data are presented as a representative blot (left panel) and a summary graph of quantified TSC2 (right panel) protein bands relative to the level of β-Actin.",
    "ncbi_link": "TSC1: 64930
TSC1: 7248"
  },
  {
    "caption": "D Co-immunoprecipitation analysis of the interaction between endogenous TSC2 and exogenous TSC1 wildtype and K30A in TSC1-KO MEFs transfected (for 48 h) with (+) or without (-) the indicated expression vectors. KO MEF cells were transfected with indicated expression plasmids. The right panel is a summary graph of TSC2/TSC1 ratio based on quantification of the last four lanes of the anti-Flag IP blot in left panel.",
    "ncbi_link": "TSC1: 64930"
  },
  {
    "caption": "E Analysis of ubiquitin conjugation to endogenous TSC2 in TSC1-KO MEFs transfected (for 48 h) with (+) or without (-) TSC1 WT or K30A and treated with MG132 for 2 h before lysis.",
    "ncbi_link": "TSC1: 64930
TSC1: 7248"
  },
  {
    "caption": "F Immunoblot analysis of endogenous TSC2 in TSC1-KO MEFs transfected (for 48 h) with Myc-TSC1 wildtype or K30A and subsequently treated with cycloheximide (10 μg/ml) for the indicated time periods before lysis. The right panel is a summary graph of quantified TSC2 WT and K30A protein bands presented as percentages of the level in the untreated (0 min) lane.",
    "ncbi_link": "Myc: 
TSC1: 64930
TSC1: 7248"
  },
  {
    "caption": "A. The unfertilized oocytes were injected with spermatozoa with a variant in IQCN at 15-18 h post-injection. The white arrowheads represent the polar body (PB). PN represents pronucleus.",
    "ncbi_link": "IQCN: 80726"
  },
  {
    "caption": "A. Fertility assessment experiments in WT and Iqcn-/- male mice after mating with WT female mice (n = 18).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "B. Size of the testes and epididymides in WT and Iqcn-/- male mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "C. Quantification ratio of the testis weight/body weight in WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "D. Sperm counts in the caudal epididymis from WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "E. H&E staining of sperm from WT and Iqcn-/- male mice. Red arrowheads represent sperm with no sickle shape heads.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "F. Percentage of sperm without sickle shape heads from WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "G. Ultrastructure of spermatozoa from WT and Iqcn-/- male mice. Ac represents the acrosome.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "H. Immunostaining of lectin (green) in spermatozoa from WT and Iqcn-/- male mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "I. Percentage of abnormal acrosomes in spermatozoa from WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "J. Percentage of spontaneous and induced acrosome reactions in spermatozoa from WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "A. Representative two pronucleus (2PN) zygotes, two-cell embryos, and blastocysts after ICSI in WT and Iqcn-/- male mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "B. Percentage of 2PN zygotes, two-cell embryos and blastocysts after ICSI in WT and Iqcn-/- male mice (n = 3).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "C. Profile of Ca2+ responses induced by oocyte injection with spermatozoa from WT and Iqcn-/- male mice (n = 5). Spermatozoa from WT male mice induced 8-9 Ca2+ spikes over a 3-h period (blue line), while spermatozoa from Iqcn-/- male mice failed to induce spikes (red line).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "D. Immunostaining of oocytes injected with spermatozoa from WT and Iqcn-/- male mice. The expression of PLCζ (red) and α-tubulin (green) was detected in oocytes. M represents male nucleus and F represents the female nucleus.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "E. Expression and localization of PLCζ in sperm from WT and Iqcn-/- male mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "F. Expression and localization of PLCζ during acrosomal biogenesis from WT and Iqcn-/- male mice. PLCζ was localized in the acroplaxome in WT spermatids. PLCζ was only localized in the tip of the head in the cap and acrosome phases (white arrowheads) and was lost during the maturation phase in Iqcn-/- mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "B. Ultrastructure of the testes from WT and Iqcn-/- male mice from steps 8-16. MA represents manchette. PR represents perinuclear ring. CD represents cytoplasmic droplets. Scale bars, 2 μm (steps 8-12; 15-16) and 5 μm (steps 13-14).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "D. Length of the manchette structure in spermatids at steps 13-14 from WT and Iqcn-/- male mice (n = 10).",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "A. Expression and localization of calmodulin during spermiogenesis in the testes of WT and Iqcn-/- male mice. Calmodulin (red) was co-localized with α-tubulin (green) from steps 8-14 in WT mice, but failed to co-localize in steps 13-14 in Iqcn-/- male mice.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "B. Interaction between IQCN and calmodulin (CaM) following co-IP by IQCN antibody in testes from WT and Iqcn-/- male mice (n = 3). IQCN interacts with calmodulin in WT mice, the interaction of which is completely lost in Iqcn-/- male mice. GAPDH was used as the internal control.",
    "ncbi_link": "Iqcn: 637079"
  },
  {
    "caption": "C. Immunostaining of calmodulin (red) and α-tubulin (green) in HeLa cells. The normal (WT) and mutant (c.910C>T and c.2453_2454del) plasmids of IQCN were transfected into HeLa cells. HeLa cells were treated with an antagonist of calmodulin W-7. Multipolar spindles were observed in HeLa cells transfected with mutant plasmids and W-7 treatment.",
    "ncbi_link": "IQCN: 80726"
  },
  {
    "caption": "D. Percentage of multipolar spindles in WT and mutant IQCN transfected HeLa cells. (n = 3 biological replicates)",
    "ncbi_link": "IQCN: 80726"
  },
  {
    "caption": "(B-F) Basal views through living SCs, with dashed white circles approximating the outline of a single SC, and acidic compartments marked by the vital dye LysoTracker® Red (magenta). In merge images, a single non-acidic (C, D, F) and acidic (E) compartment containing intraluminal vesicles (ILVs) is boxed and magnified in the right panel (Zoom). ILVs appear as membrane-delineated vesicles, using super-resolution 3D-structured illumination (3D-SIM) microscopy for the brighter overexpressed GFP-tagged constructs (yellow; C and F). However, ILVs appear only as puncta, using lower resolution wide-field microscopy for the fainter endogenously expressed YFP-tagged Rab GTPases (yellow; D and E). (B) Wide-field fluorescence image, including differential interference contrast (DIC), of SC expressing a GFP-tagged version of human CD63 (CD63-GFP). CD63-GFP expression is apparent on the limiting membranes of non-acidic compartments and their ILVs, and also on the limiting membranes of the enlarged acidic compartments. Most large non-acidic compartments are Rab11-positive (D) and contain dense-core granules, which have a 'fried egg' appearance with DIC (arrowheads) (Corrigan et al., 2014; Redhai et al., 2016). (C) 3D-SIM image of CD63-GFP-expressing SC. Arrow highlights CD63-GFP-marked ILVs (Zoom). Many more ILVs are apparent in non-acidic compartments in a complete Z-stack of a non-acidic compartment (Movie EV1). (D) Wide-field fluorescence image of an SC expressing a YFP-Rab11 gene trap. YFP-Rab11 marks the limiting membranes of most non-acidic compartments and internal puncta (arrow in Zoom), but not the surface of acidic compartments (Appendix Fig S1B). (E) Wide-field fluorescence image of SC expressing a YFP-Rab7 gene trap. YFP-Rab7 marks the limiting membranes of acidic compartments and internal puncta (arrow in Zoom). Enlarged acidic compartments are also present in adjacent main cells. (F) 3D-SIM image of SC expressing a GFP-tagged version of Breathless (Btl-GFP). Btl-GFP marks the limiting membranes of non-acidic compartments and their ILVs (arrow in Zoom), but not the surface of acidic compartments (Appendix Fig S1C). Images from six-day-old male flies shifted to 29°C at eclosion. This induces GAL4/UAS-dependent SC transgene expression in (B), (C) and (F). The genotypes of flies carrying multiple transgenes are: w; P[w+, UAS-CD63-GFP] P[w+, tub-GAL80ts]/+; dsx-GAL4/+ (B, C); w; P[w+, tub-GAL80ts]/+; dsx-GAL4/P[w+, UAS-btl-GFP] (F).",
    "ncbi_link": "CD63: 
GAL4: 
GAL80: 
GFP: 
tub: 
YFP: 
Breathless: 39564
Btl: 39564
btl: 39564
CD63: 967
dsx: 40940
Rab11: 42501
Rab7: 42841"
  },
  {
    "caption": "(A-D) Wide-field fluorescence images of basal views through living SCs expressing a GFP-tagged form of Btl-GFP (yellow) in non-acidic compartments, with SC outline approximated by dashed white circles. Acidic compartments are marked by LysoTracker Red® (magenta). Boxed non-acidic compartments in merge images are magnified in A-D, Zoom. On the right, lower magnification confocal transverse images of fixed accessory gland (AG) lumens are shown with dotted lines indicating the basal side of the AG epithelial layer, which contains several fluorescent SCs (highlighted by arrows). (A) SC with no RNAi construct expressed (control) and AG lumen from same genotype. Btl-GFP-positive compartments containing fluorescent ILVs (in Btl-GFP panel), ILV membranes inside compartments (in Zoom panel) and secreted fluorescent puncta (AG lumen panel) are marked by arrowheads. (B) SC also expressing RNAi construct targeting ESCRT-0 subunit, Stam, and AG lumen from same genotype. Btl-GFP-positive ILVs (Zoom) and secreted puncta (AG lumen) are strongly reduced. (C) SC also expressing RNAi construct targeting ESCRT-I subunit, Vps28, and AG lumen from same genotype. Btl-GFP-positive ILVs (Zoom) and secreted puncta (AG lumen) are strongly reduced. (D) SC also expressing RNAi construct targeting ESCRT-III subunit, shrb, and AG lumen from same genotype. Btl-GFP-positive ILVs (Zoom) and secreted puncta are strongly reduced. Genotypes are: w; P[w+, tub-GAL80ts]/+; dsx-GAL4/P[w+, UAS-btl-GFP] with no knockdown construct (A), UAS-Stam-RNAi (HMS01429; B), UAS-Vps28-RNAi (v31894; C) or UAS-shrb-RNAi (v106823; D).",
    "ncbi_link": "GAL4: 
GAL80: 
GFP: 
tub: 
Btl: 39564
btl: 39564
dsx: 40940
shrb: 35933
Stam: 34505
Vps28: 47408"
  },
  {
    "caption": "(E) Super-resolution 3D-SIM image of fixed HCT116 cell expressing GFP-Rab11a (yellow), and stained with CD63 (magenta). DAPI (grey) marks nucleus. Boxed Rab11a-positive compartments, which frequently cluster, are magnified in Merge Zoom. This panel is further magnified in Merge Zoom x 2, revealing GFP-Rab11a (arrows in right panel) inside compartments.",
    "ncbi_link": "GFP: 
Rab11a: 8766"
  },
  {
    "caption": "(F) Wide-field fluorescence image of fixed HCT116 cells, stained with Rab11a (yellow) and Rab7 (magenta), expressing constitutively active GFP-tagged Rab5 (GFP-Rab5CA; cyan), which stalls endosomal maturation and produces enlarged Rab5-positive endosomes. One of these is boxed in the Merge and magnified in Merge Zoom, revealing internal puncta marked by Rab11a (arrows) and Rab7 (arrowheads) and limiting membrane subdomains of Rab11a (yellow arrowhead) and Rab7 (magenta arrowhead). DAPI (grey) marks nuclei.",
    "ncbi_link": "GFP: 
Rab5: 5868"
  },
  {
    "caption": "Western blot analyses of EV preparations. Gel loading is normalised to cell lysate protein levels. Bar charts present changes in levels of putative exosome proteins relative to cell lysate protein (D) EVs isolated by UC from HCT116 cells cultured for 24 h following three days of raptor or non-targeting (NT) shRNA knockdown.",
    "ncbi_link": "raptor: 57521"
  },
  {
    "caption": "(C) Western blot analysis of EVs isolated by UC from HCT116 cells cultured in glutamine-replete and -depleted medium for 24 h, following transduction with a Rab11a or control non-targeting (NT) shRNA knockdown construct over previous two days. Bar chart shows change in putative exosome proteins in EVs secreted from Rab11a knockdown cells relative to NT-treated cells in glutamine-depleted conditions, following initial normalisation to cell lysate protein. (C') Growth curves are for HCT116 recipient cells pre-treated with EVs isolated as in (C) or with vehicle (PBS). ****P colour denotes significant increase relative to EVs from glutamine-replete cells (black) and Rab11a knockdown cells (red).",
    "ncbi_link": "Rab11a: 8766"
  },
  {
    "caption": "(F) Western blot analysis of EVs isolated by UC from HCT116 cells in glutamine-replete medium, transduced with a Rab7 or non-targeting (NT) control shRNA knockdown construct. Bar charts show changes in putative exosome proteins in EVs isolated by ultracentrifugation, following normalisation to cell lysate protein. (F') Growth curves are for HCT116 recipient cells pre-treated with EVs isolated as in (F) or with vehicle (PBS).",
    "ncbi_link": "Rab7: 42841"
  },
  {
    "caption": "(A) A northern blot depicting a time course experiment ranging from five minutes to 24 hours of MCF10A cells in response to oxidative stress. A single probe complementary to pre-tRNATyrGUA, mature tRNATyrGUA, and tRFTyrGUA expression was 32P-labeled and used for detection. (B) Quantification of pre-tRNATyrGUA (left) and mature tRNATyrGUA levels (right) by northern blot analysis from multiple independent experiments (normalized to U6 levels) are shown (n=6). ",
    "ncbi_link": "U6: "
  },
  {
    "caption": "(C) MCF10A cells were exposed to oxidative stress (200μM H2O2) once daily for five continuous days. (D) Quantification of mature tRNATyrGUA bands by northern blot after cells were treated once daily for five continuous days (normalized to U6) from multiple independent experiments (n=12). ",
    "ncbi_link": "U6: "
  },
  {
    "caption": "(C) Western blot of MCF10A expressing a control short-hairpin RNA or a hairpin targeting the tyrosine-tRNA synthetase, YARS (red arrow). HSC70 was used as a loading control.",
    "ncbi_link": "tyrosine-tRNA synthetase: 8565"
  },
  {
    "caption": "(D) Growth curves of MCF10A cells expressing RNAi targeting mature tRNATyrGUA or YARS relative to cells expressing a control hairpin (n=3). Two-way ANOVA was used to test for significance.",
    "ncbi_link": "YARS: 8565"
  },
  {
    "caption": "(A) Cells depleted of tRNATyrGUA or YARS were processed for label free quantitation by mass spectrometry to identify proteins that were reduced by a log2-fold change of 0.5 or more. This set was overlapped with proteins containing a higher than median abundance of Tyr codon content to identify candidate mediators of the pleiotropic effects of tRNATyrGUA depletion.",
    "ncbi_link": "YARS: 8565"
  },
  {
    "caption": "(E) Growth curves for MCF10A cells were transfected with either control siRNA or two independent siRNA targeting EPCAM, SCD, or USP3. Note that the control cell growth curve is the same in all graphs and were plotted separately for clarity and does not represent independent experiments. Two-way ANOVA was used to test for significance (n=3).",
    "ncbi_link": "EPCAM: 4072
SCD: 6319
USP3: 9960"
  },
  {
    "caption": "(E) A cumulative distribution in control and hnRNPA1 depleted cells of the stability levels for mRNA transcripts with 3' UTR hnRNPA1 CLIP binding (Huelga et al., 2012). Transfection of tRFTyrGUA led to a significant right-shift in the expression levels of 3' UTR bound hnRNPA1 transcripts. Statistical significance was measured using the Kolmogorov-Smirnov test. (F) Cumulative distribution as in (E). Transfection of locked nucleic acid against tRFTyrGUA and treatment with 200µM H2O2 led to a significant left-shift in mRNA stability of 3'UTR bound hnRNPA1 transcripts. Statistical significance was assessed using the Kolmogorov-Smirnov test. ",
    "ncbi_link": "hnRNPA1: 3178"
  },
  {
    "caption": "(H, I) Representative H&E (H) and dystrophin immunofluorescence of images of TA muscle cross-sections in WT and Prmt5MKO mice. Scale bar: 100 μm.",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(J, Distribution of myofiber size (J) of WT (n=4) and Prmt5MKO TA muscles (n=4).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(L) The total number of myofibers in EDL and Soleus from WT (n=5) and Prmt5MKO mice (n=6).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(B-D) Exercise performance of maximum speed (B), running time (C), running distance (D) of WT (n=11) and Prmt5MKO mice (n=9) measured by treadmill.",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(E, F) Absolute (E) and specific force (F) (on the left panel) and maximal absolute and specific force (on right panel) on EDL muscle from WT (n=4) and Prmt5MKO mice (n=3). (G, H) Absolute (G) and specific force (H) (on the left panel) and maximal absolute and specific force (on right panel) on Soleus muscle from WT (n=4) and Prmt5MKO mice(n=3).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(A) Representative immunostaining of Type I, IIA, and IIB myofibers in in EDL and Soleus muscles of 2-month-old WT and Prmt5MKO mice. (B, C) Quantification of abundance of various fiber types in EDL (B) and Soleus (C) muscles of WT and Prmt5MKO mice; (n=5).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(D) Representative histochemical staining image of succinate dehydrogenase (SDH) enzymatic activity in EDL and Soleus muscles. (E, F) Quantification of abundance of SDH-low, -medium and -high myofibers in EDL (E) and Soleus (F) muscles of WT (n=5) and Prmt5MKO mice (n=4).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(G, H) Metabolic rate of O2 consumption (G) and CO2 production (H) normalized to lean mass for a 48-hour cycle of 4-6-month-old WT (n=8) and Prmt5MKO (n=7) mice measured by an indirect calorimetry.",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(A, B) Representative images of ORO staining (A) and immunofluorescence (B) in TA muscle from WT and Prmt5MKO mice. Scale bar: 100 μm.",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(C) Western blotting analysis for protein markers of lipolysis, lipogenesis, and electron transport chain (ETC) complexes in skeletal muscles of WT (n=3) and Prmt5MKO mice; (n=3).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(A) C2C12 cells overexpressing PRMT5-GFP alone or PRMT5-GFP + SREBP1a-Flag were immunoprecipitated with Flag antibody and blotted with SYM10, GFP, Flag, PRMT5, and Tubulin antibodies. (B) C2C12 cells overexpressing SREBP1a-Flag alone or SREBP1a-Flag + PRMT5-GFP were immunoprecipitated with GFP antibody and blotted with Flag, GFP, PRMT5, and Tubulin antibodies.",
    "ncbi_link": "Flag: 
GFP: 
PRMT5: 10419
SREBP1a: 6720"
  },
  {
    "caption": "(E) HEK293 cells were transfected with PRMT5-GFP alone or PRMT5-GFP + SREBP1a-Flag for 24 hours, followed by cycloheximide (30 μg/ml) and protein analysis at 0, 4, 8 hours. Lysates were immunoblotted with Flag, GFP, and tubulin antibodies.",
    "ncbi_link": "Flag: 
GFP: 
PRMT5: 10419
SREBP1a: 6720"
  },
  {
    "caption": "(G) Relative expression of lipogenesis genes (Dgat1, Dgat2, Fabp4) in C2C12 transfected with PRMT5 and SREBP1a; (n=4, technical replicates).",
    "ncbi_link": "Dgat1: 13350
Dgat2: 67800
Fabp4: 11770
PRMT5: 10419
SREBP1a: 6720"
  },
  {
    "caption": "(A, B) Immunoblots showing symmetric demethylation of H4R3 in skeletal muscles of WT (n=4) and Prmt5MKO mice (n=4) (A), and quantification of H4R3Me2s normalized to total H4 (B).",
    "ncbi_link": "Prmt5: 27374"
  },
  {
    "caption": "(E) ChIP-sequencing results showing the Prmt5 binding peak on the Pnpla2 promoter of 3T3-L1 cells.",
    "ncbi_link": "Pnpla2: 66853"
  },
  {
    "caption": "(H, I) Enrichment of PRMT5 (H) and H4R3Me2s (I) on the proximal promoter region of the Pnpla2 gene in skeletal muscles of WT and Prmt5MKO mice (n=4 for H, and I, biological replicates).",
    "ncbi_link": "Pnpla2: 66853
Prmt5: 27374"
  },
  {
    "caption": "(D) Immunoblotting analysis showing PRMT5, ATGL and ETCs in muscle tissues (upper panel) and quantification of its relative protein levels in muscles of WT, Prmt5MKO, and Prmt5/Pnpla2MKO mice (bottom panel) (n=2, biological replicates).",
    "ncbi_link": "Pnpla2: 66853
Prmt5: 27374"
  },
  {
    "caption": "(E, F) Exercise performance in running distance (E) and griping strength test (F) in WT (n=11 for E, n=8 for F), Prmt5MKO (n=10 for E, n=9 for F) and Prmt5/Pnpla2MKO mice (n=9 for E, n=8 for F).",
    "ncbi_link": "Pnpla2: 66853
Prmt5: 27374"
  },
  {
    "caption": "(I) Representative images of ORO staining in TA muscles under brightfield (upper panel) and fluorescent imaging (bottom panel) from WT, Prmt5MKO, and Prmt5/Pnpla2MKO mice. Scale bar: 50 μm.",
    "ncbi_link": "Pnpla2: 66853
Prmt5: 27374"
  },
  {
    "caption": "(b) A53T α-synuclein (α-syn) expression was induced in stable PC12 cells for 48 h, then switched off for 24 h. Cells were treated with DMSO (control), or with 0.94 μM, 4.7 μM or 47 μM of SMER10; 0.86 μM, 4.3 μM or 43 μM of SMER18; or 0.9 μM, 4.7 μM or 47 μM of SMER28 added in the switch-off period. A53T α-syn levels were analyzed by immunoblotting with antibody against HA (left) and densitometry analysis relative to actin (right). Error bars denote s.e.m. P = 0.0917, P = 0.009, P = 0.0001 (for increasing concentrations of SMER10); P = 0.0068, P = 0.0023, P = 0.0002 (for increasing concentrations of SMER18); P = 0.0016, P 0.0001, P 0.0001 (for increasing concentrations of SMER28).",
    "ncbi_link": "α-synuclein: 6622"
  },
  {
    "caption": "(d) Wild-type (Atg5+/+) and knockout (Atg5−/−) Atg5 MEFs were transfected with EGFP-HDQ74 and treated with DMSO (control), 47 μM SMER10, 43 μM SMER18 or 47 μM SMER28 for 24 h, and we assessed the percentages of aggregate-containing transfected cells. The control (DMSO-treated) values were fixed at 1 for both cell lines. Error bars: 95% confidence interval. P = 0.039 (SMER10), P 0.0001 (SMER18 and SMER28) (in Atg5+/+ cells); P = 0.092 (SMER10), P = 0.271 (SMER18), P = 0.358 (SMER28) (in Atg5−/− cells). Note that EGFP-HDQ74 aggregation was higher in Atg5−/− than in Atg5+/+ cells (Supplementary Fig. 3a).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) COS-7 cells transfected with EGFP-LC3 construct for 4 h were treated with DMSO (control), 0.2 μM rapamycin (positive control), 47 μM SMER10, 43 μM SMER18 or 47 μM SMER28 for 16 h, and analyzed by fluorescence microscopy. The effects of treatment on the percentage of EGFP-positive cells with >5 EGFP-LC3 vesicles are shown. Error bars denote s.e.m. P 0.0001 (all SMERs).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(b) HeLa cells stably expressing EGFP-LC3 were treated with DMSO (control), 47 μM SMER10, 43 μM SMER18 or 47 μM SMER28 for 24 h. Confocal sections show cells containing EGFP-positive autophagic vesicles. Nuclei are stained with DAPI. Bar, 20 μM.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(c) HeLa cells stably expressing EGFP-LC3 were treated for 4 h with DMSO (control) or 200 nM bafilomycin A1 (Baf), or with 200 nM bafilomycin A1 and 47 μM SMER10, 43 μM SMER18 or 47 μM SMER28. Cells were left untreated or pretreated with SMERs for 24 h before adding bafilomycin A1. Levels of EGFP-LC3-II were determined by immunoblotting with antibody against EGFP (above) and densitometry analysis relative to actin (below). Error bars denote s.e.m. P = 0.0259 (baf), P 0.0001 (SMER10), P = 0.0003 (SMER18 and SMER28) versus control; P = 0.0025 (SMER10), P = 0.0218 (SMER18), P = 0.0195 (SMER28) versus bafilomycin A1. ***P 0.001; **P 0.01; *P 0.05.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A)  RT-qPCR measurement of intracellular level of the SARS-CoV-2 RNA  in Huh7  cells after 72 hours and 96 hours of infection. Data information: In A values were normalized to that of the GAPDH  and represented as mean±SD of samples from five independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(C-J) RT-qPCR analysis of the intracellular mRNA levels of HERV-T (C), HERV-E (D), HERV-R (E), HERV-V (F), HERV-FRD  (G), HERV-MER34  (H), HERV-W (I) and HERV-K-HML-2 (J) in the SARS-CoV-2 infected Huh7  cells, as mentioned in (A). Data information: In C-J, values were normalized to that of the GAPDH  and represented as mean±SD of samples from five independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "HERV-E: 
HERV-MER34: 
GAPDH: 2597"
  },
  {
    "caption": "(A) RT-qPCR  measurement of intracellular level of the SARS-CoV-2 RNA  (normalized to that of the GAPDH) in  Calu 3 cells after 48 hours and 72 hours of infection. Data information: In A values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(C-J) RT-qPCR analysis of the intracellular mRNA levels of HERV-T  (C), HERV-E (D), HERV-R (E), HERV-V (F), HERV-FRD (G), HERV-MER34 (H), HERV-W (I) and HERV-K-HML-2 (J) in the SARS-CoV-2 infected  Calu 3  cells, as mentioned in (A). Data information: In C-J, values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "HERV-E: 
HERV-MER34: 
GAPDH: 2597"
  },
  {
    "caption": "(B)  RT-qPCR measurement of exon 1 region [shown in (A)] transcript in Huh7  cells infected with SARS-CoV-2 for 72hours. (C) RT-qPCR  measurement of exon 1 region transcript in  Calu 3  cells infected with SARS-CoV-2 for 72hours. Data information: In B and C, values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(E) RT-qPCR measurement of  HERV-R-Env  transcript level in PBMCs  isolated from 19 healthy individuals and 16 COVID-19 patients. (F) RT-qPCR measurement of Exon1 region transcript level in PBMCs  isolated from 19 Healthy individuals and 16 COVID-19 patients. Data information: values were normalized to that of the GAPDH  and represented as mean±SD of samples from 19 healthy and 16 COVID-19 patients, assayed in duplicate.",
    "ncbi_link": "Env: 
GAPDH: 2597"
  },
  {
    "caption": "(G) Quantitation of HERV-R-Env  RNA level in transcriptome dataset of indicated human lung  tissues Data information: In G, HERV-R-Env  copy number in two biological replicates (Healthy lung) and two technical replicates (COVID-19 lung) of the transcriptome dataset are represented as mean±SD.",
    "ncbi_link": "Env: "
  },
  {
    "caption": "(H) Quantitation of HERV-R-Env  RNA level in transcriptome dataset of Calu 3 cells, analyzed at 4, 8, 12 and 24 hours of SARS-CoV-2  infection, as indicated. Data information: In H, HERV-R-Env  copy number in three biological replicates of the transcriptome dataset are represented as mean±SD. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "Env: "
  },
  {
    "caption": "(A) RT-qPCR measurement of intracellular level of the  SARS-CoV-2 delta variant  RNA  in Huh7  and Calu 3  cells after 24, 48 and 72 hours of infection. (B) RT-qPCR measurement of intracellular level of the SARS-CoV-2 omicron variant RNA  in Huh7  and  Calu 3  cells after 24, 48 and 72 hours of infection. Data information: values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(C) RT-qPCR analysis of the HERV-R-Env  RNA level in the SARS-CoV-2 delta variant infected Huh7  and Calu 3  cells, as mentioned in (A). (D)  RT-qPCR analysis of the HERV-R-Env  RNA level in the SARS-CoV-2 omicron variant infected Huh7  and Calu 3 cells, as mentioned in (B). Data information: values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "Env: 
GAPDH: 2597"
  },
  {
    "caption": "(F) RT-qPCR  measurement of intracellular level of the SARS-CoV-2 RNA  (normalized to that of the GAPDH) in Huh7  cells transfected with NT-siRNA (Non target siRNA) or HERV-R-Env  siRNA and infected with the SARS-CoV-2 for 24, 48 or 72 hrs, as indicated. Values are mean±SD of 3 independent experiments. Data information: In F, values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments.",
    "ncbi_link": "Env: 
GAPDH: 2597"
  },
  {
    "caption": "(G) Dual luciferase assay showing activation of IFNγ, ISRE, ISG56  and NFκB  promoters in  HEK 293T cells expressing the empty vector (V), constitutively active mutant of RIG-I, R-C, 25 and 50 ng of  HERV-R-Env. Activation of these promoters by R-C was taken as 100%. Data information: In G, FF Luc  values were normalized to that of the RL Luc  and represented as % mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "Env: 
Luc: 
ISG56: 3434
NFκB: 4790
RIG-I: 23586"
  },
  {
    "caption": "(H) Western blot  analysis of the indicated proteins in Huh7  cells, transiently transfected with HERV-R-Env  expression plasmid.",
    "ncbi_link": "Env: "
  },
  {
    "caption": "(B) HERV-R 5'-LTR activity in Huh7  cells cotransfected with the pGL3 Fl 5'-LTR G-Luc  and pGL3 promoter Firefly-Luc  (denoted as Fl 5'-LTR  G-Luc) or pGL3  G-Luc  and pGL3 promoter Firefly-Luc  (denoted as G-Luc) plasmids for 48 hours. (C) HERV-R  5'-LTR activity in Huh7  cells cotransfected with the pGL3 Fl 5'-LTR G-Luc   and pGL3 promoter Firefly-Luc  (denoted as Fl 5'-LTR  G-Luc) or pGL3 ∆ 5'-LTR G-Luc  and pGL3 promoter Firefly-Luc  (denoted as ∆ 5'-LTR G-Luc) or pGL3 G-Luc  and pGL3 promoter Firefly-Luc  (denoted as  G-Luc) plasmids for 48 hours. Data information: G-Luc   values were normalized to that of the Firefly-Luc  and represented as mean±SD of samples from three independent experiments.",
    "ncbi_link": "G-Luc: 
Luc: "
  },
  {
    "caption": "(I) RT-qPCR measurement of HERV-R-Env  RNA in Huh7  cells infected with the SARS-CoV-2  and treated with the indicated compounds for 48 hours. Data information: In I values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "Env: 
GAPDH: 2597"
  },
  {
    "caption": "(K)  RT-qPCR measurement of intracellular level of the SARS-CoV-2 RNA  in Huh7  cells infected with the  SARS-CoV-2 and treated with the indicated compounds for 48 hours. Data information: In K, values were normalized to that of the GAPDH  and represented as mean±SD of samples from three independent experiments. Student's t-test was applied to determine the significance between the groups.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "G. Schematic diagram of human TRIM50  (WT) and its truncation mutants was presented(top), and the interaction  of TRIM50   (TRIM50   truncation mutants) and NLRP3  was detected by IP  assay. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "TRIM50: 135892"
  },
  {
    "caption": "H, I. Schematic diagram of human NLRP3  (WT) and its truncation mutants (top), and immunoprecipitation  assay of the interaction  of NLRP3  (NLRP3  truncation mutants) with TRIM50  in HEK293T  cells. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "A. Immunoblot  analysis of the NLRP3  protein level in the mouse peritoneal macrophages  transfected with Si-Trim50. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-tailed Student's t-test (A, Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "B.  qRT-PCR analysis of Nlrp3  and IL-1β mRNA levels in LPS-primed Si-Trim50  transfected mouse peritoneal macrophages. Data information: P-values are shown, two-way analysis of variance (ANOVA) (B, Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "IL-1β: 16176
Nlrp3: 216799
Trim50: 215061"
  },
  {
    "caption": "C, D. Immunoblot  analysis of Caspase1-P20 (C) and  Gasdermin D (D) of WT or Trim50-/- mouse peritoneal macrophages after LPS  stimulation for 6h and ATP  treatment for 30min. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "E, Immunoblot  analysis of  Caspase1-P20 (E) of WT or Trim50-/- BMDM  cells after LPS  stimulation for 6h and ATP  treatment for 30min. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "F. Immunoblot  analysis of Gasdermin D  (F) of WT or Trim50-/- BMDM  cells after LPS  stimulation for 6h and ATP  treatment for 30min. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "G, ELISA  analysis of  IL-1β, TNF-α and IL-6 in the supernatant of WT or Trim50-/- peritoneal macrophages with the activation of NLRP3  inflammasome. n=3 Data information: P-values are shown, two-way analysis of variance (ANOVA) G, Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "H. ELISA  analysis of  IL-1β, TNF-α  and  IL-6 in the supernatant of WT or Trim50-/- BMDM  cells with the activation of NLRP3  inflammasome. n=3 Data information: P-values are shown, two-way analysis of variance (ANOVA) Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "I. LDH  analysis of WT or Trim50-/- mouse peritoneal macrophages  with the activation of NLRP3  inflammasome. n=3 Data information: P-values are shown, two-way analysis of variance (ANOVA) I). Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "A. Immunoprecipitation  analysis of the NLRP3 ubiquitination  in HEK293T  cells transfected with HA-ubiquitin, His-NLRP3  and Flag-TRIM50   plasmids. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Flag: 
HA: 
His: 
NLRP3: 114548
ubiquitin: 6233///7311///7316///7314
TRIM50: 135892"
  },
  {
    "caption": "B. Immunoprecipitation  analysis of the endogenous NLRP3 ubiquitination  in WT or Trim50-/- BMDM  cells. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "C. Immunoprecipitation  analysis of NLRP3 ubiquitination  in HEK293T  cells transfected with NLRP3, HA-Ubiquitin, TRIM50   or TRIM50   (ΔRING) mutant plasmids. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "HA: 
NLRP3: 114548
Ubiquitin: 6233///7311///7316///7314
TRIM50: 135892"
  },
  {
    "caption": "F. Immunoblot  analysis of NLRP3  in HEK293T  cells transfected with NLRP3  plasmid and TRIM50  or TRIM50   (ΔRING) mutant, followed with the further treatment with CHX  for 0h, 4h or 8h. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-way ANOVA Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "A. SDD-AGE analysis of NLRP3 oligomerization  in HEK293T cells transfected with NLRP3  and TRIM50   plasmids. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "B.  SDD-AGE  analysis of NLRP3 oligomerization  in NLRP3  and TRIM50   transfected HEK293T  cells followed with nigericin  treatment for 30min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "C. Immunoblot  analysis of ASC oligomerization  in cross-linked cytosolic  pellets (insoluble) and whole cell lysate (soluble) in HEK293T  cells transfected with NLRP3, ASC  and TRIM50   plasmids followed with nigericin   treatment for 30 min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
ASC: 29108
TRIM50: 135892"
  },
  {
    "caption": "D. SDD-AGE analysis of NLRP3 oligomerization  in WT or Trim50-/- peritoneal macrophages  with LPS  treatment for 6h and ATP  treatment for 30 min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "E. Immunoblot  analysis of ASC oligomerization  in cross-linked cytosolic  pellets (insoluble) and whole  cell lysate (soluble) in WT or Trim50-/- peritoneal macrophages by LPS  stimulation for 6h and ATP  treatment for 30min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "F. SDD-AGE  analysis of NLRP3 oligomerization  in WT or Trim50-/- BMDM  cells with LPS  treatment for 6h and ATP  treatment for 30 min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "G. Immunoblot  analysis of ASC oligomerization  in cross-linked cytosolic  pellets (insoluble) and whole  cell lysate (soluble) in WT or Trim50-/- BMDM  cells by LPS  stimulation for 6h and ATP  treatment for 30min. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "H. SDD-AGE  analysis of the oligomerization   of NLRP3  in HEK293T  cells transfected with His-NLRP3  and TRIM50   or TRIM50(ΔRING) mutant. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "His: 
NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "J. Immunoprecipitation  analysis of NLRP3 ubiquitination  in HA-ubiquitin, His-NLRP3  and Myc-TRIM50  transfected HEK293T  cells with further treatment with tranilast  or MCC950  for 24h. Data information: Data are representative of three biological replicates with similar results.",
    "ncbi_link": "His: 
Myc: 
NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "A. Immunoprecipitation  analysis of NLRP3 ubiquitination  in HEK293T  cells transfected with NLRP3, HA-Ubiquitin, TRIM50   or its truncation mutants. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "B. SDD-AGE analysis of NLRP3 oligomerization  in NLRP3   together with TRIM50   or its coiled-coil domain-deleted mutants (ΔC-C1 and ΔC-C2) transfected HEK293T  cells. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "C. SDD-AGE  analysis of the oligomerization  of TRIM50   in TRIM50   or its coiled-coil domain-deleted mutants (ΔC-C1 and ΔC-C2) transfected HEK293T  cells. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "TRIM50: 135892"
  },
  {
    "caption": "D. SDD-AGE analysis of the oligomerization  of NLRP3  and TRIM50   in HEK293T  cells overexpressing NLRP3  together with TRIM50   or its coiled-coil domain-deleted mutants. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "E. Immunoblot  analysis of NLRP3  in HEK293T  cells transfected with NLRP3  plasmid and TRIM50   coiled-coil domain-deleted mutants, followed with the cycloheximide  (CHX) treatment for 0h, 4h or 8h. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. P-values are shown, two-way ANOVA(E). Data are representative of three biological replicates with similar results. (mean ± SD in E).",
    "ncbi_link": "NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "F. Immunoblot  analysis of ASC oligomerization  in cross-linked cytosolic  pellets (insoluble) and whole cell lysate(soluble) in HEK293T  cells transfected with His-NLRP3  and TRIM50   or TRIM50   coiled-coil domain-deleted mutants. Data information: Band densities were quantitated by 'Image J' software and normalized to GAPDH. Data are representative of three biological replicates with similar results.",
    "ncbi_link": "His: 
NLRP3: 114548
TRIM50: 135892"
  },
  {
    "caption": "A. Survival  status of WT and Trim50-/- mice  after intraperitoneal injection with LPS  (n=10 mice/group). Data information: P-values are shown, two-way ANOVA (A) Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "B. ELISA  analysis of  IL-1β, TNF-α and IL-6 in serum  of WT or Trim50-/- mice  after i.p. injection with LPS  for 6h (n=4-6 mice/group). Data information: P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "D. Flow cytometry analysis of the neutrophils  (left) and  Ly6C+ monocytes  (right) in peritoneum  of WT or Trim50-/- mice  after i.p. injection with Alum. (n=6 mice/group). Data information: P-values are shown, two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "E. WT or Trim50-/- mice  were i.p. injected with FA  for 36h, followed with immunoblot  analysis of NLRP3, pro-IL-1β, Caspase1 p20, IL-1β in the kidney  tissue samples. Data information: P-values are shown, two-way ANOVA (A) or two-tailed Student's t-test Data are representative of three biological replicates with similar results. (mean ± SD",
    "ncbi_link": "Trim50: 215061"
  },
  {
    "caption": "B-C') Immunofluorescence analysis of active-caspase 3 in the ONL of P347S and P347S/miR-181a/b+/-. D, E) TUNEL analysis in the ONL of P347S and P347S/miR-181a/b+/-. F) Quantification of immunofluorescence analysis in (B-C') (N=4 eyes P347S and N=6 eyes P347S/ miR-181a/b+/). G) Quantification of TUNEL analysis in (D, E) (N=3 eyes/genotype).",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "D-P) Immunofluorescence analysis showed amelioration of Rhodopsin localization (D-F'; white arrowheads); C-arrestin expression (G-I') and PR outer segment (OS) and inner segment (IS) structures, as determined, respectively, by PNA (J-L'); and Phalloidin staining (M-O'') in P347S/miR-181a/b+/- vs P347S eyes at p30. M''-O'' show higher magnification of M-O. Scale bars 25 μm in D-O'; 5μm in M''-O''. Fluorescence densitometry quantification of each staining is reported in (P), N=3 eye/genotype for each staining. WT vs P347S p values are reported in red, P347S vs P347S/miR-181a/b+/- p values are reported in black.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "D-L) Immunofluorescence analysis of Rhodopsin (D-E'), C-arrestin (F-G'), PNA (H-I'); and Phalloidin staining (J-K'') in P347S and P347S/miR-181a/b+/- retinas at p90. J''-K'' show higher magnification of J-K. Scale bars 25 μm in D-K'; 10μm in J''-K''.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Immunofluorescence analysis of Rhodopsin C-arrestin PNA and Phalloidin staining in P347S and P347S/miR-181a/b+/- retinas at p90. Fluorescence densitometry quantification of each staining is reported in (L), N=3 eye/genotype/staining.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "M) Measurement of P347S and P347S/miR-181a/b+/- ONL thickness (N≥3 eyes/genotype;",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "N) Graphical representation of the results of OKR analysis by the optokinetic tracking assays reported as cycles/degree. Visual acuity is preserved in P347S/miR-181a/b+/- animals with respect to P347S (N=4 animals/genotype).",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "B-F) Electron microscopy analysis shows an increase of mitochondrial fragmentation in P347S PRs with respect to WT and amelioration of the mitochondrial phenotype in P347S/miR-181a/b+/- vs P347S PRs at p12 and p30 (N=2 animals/genotype). M, mitochondria. G-I) The quantitative analysis of mitochondrial phenotype is expressed as measurement of the mitochondria perimeter (G), mitochondria number (H) and as the ratio of mitochondria area per the analyzed field area (I). N=2 animals/genotype.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "A) WB analysis of Drp1, one of the key proteins involved in the mitochondrial fission pathway, in the optic cup of WT, P347S DMSO-treated, P347S/miR-181a/b+/- DMSO-treated and of P347S/miR-181a/b+/- FEDRATINIB-treated (an inhibitor of the JAK2/STAT3 pathway) mice at p30.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "B) Quantification revealed that Drp1 protein levels are increased in P347S with respect to WT, and partially rescued in P347S/miR-181a/b+/-. Data are normalized to Gapdh. N ≥ 4 eye/genotype. Please note that all compared bands from WT, P347S, P347S/miR-181a/b+/- and P347S/miR-181a/b+/- with FEDRATINIB samples are from the same blots, which were cropped and shown organized in the panel for the sake of data presentation clarity (see source data).",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "C-D) qRT-PCR analysis reveals decreased levels of the Drp1 transcript and increased levels of Stat3 and Jak2 transcripts in the eyes of P347S/miR-181a/b+/- vs those of P347S animals. N≥4 eyes/genotype.",
    "ncbi_link": "Drp1: 74006
Jak2: 16452
miR-181a: 735252
Stat3: 20848"
  },
  {
    "caption": "F) Quantification of WB in A reveals decreased levels of Drp1 in P347S/miR-181a/b+/- DMSO-treated vs P347S and increased levels in P347S/miR-181a/b+/- FEDRATINIB-treated ex-vivo retinas. N≥4 eyes/genotype.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "(D-U) Immunofluorescence analysis showed amelioration of Rhodopsin localization (p30 D-G', p70 L-O'; white arrowheads) and C-arrestin (p30 H-K', p70 P-S'; white arrowheads) expression in Sponge-miR-181a/b-injected eyes vs the corresponding controls also highlighting improvement of the OS structure. At both time points the effect of amelioration was more significant and evident when the AAV2/8.CMV.GFP-Sponge-miR-181a/b was used. Scale bars are 25 μm. Fluorescence densitometry quantification of each staining is reported in T for p30 and in U for p70, N=3 eye/treatment/staining.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "A-I') Immunofluorescence analysis on central retinal sections at p30 showed ONL thickness increase, amelioration of Rhodopsin localization (A-D') and C-arrestin expression (E-H') in AAV2/8.CMV.GFP-Sponge-miR-181a/b-injected vs AAV2/8.CMV.GFP-injected rd10 eyes. Scale bars are 25 μm. Fluorescence densitometry quantification of each staining is reported in I, N=3 eye/treatment/staining.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Analysis of retinal function based on pupillary light responses (PLR) Water Maze tests. (J) PLR showed a significantly higher pupil constriction in rd10 mice injected with AAV2/8.CMV.GFP-Sponge-miR-181a/b than in AAV2/8.CMV.GFP-injected rd10 eyes, at both 10 lux and 100 lux intensity stimuli (N≥6 eyes/treatment and N=9 eyes/treatment, respectively). Data are presented as mean ± SEM. Student's t-test, unpaired.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Analysis of retinal function based on pupillary light responses (PLR) Water Maze tests. (K) Water Maze test highlighted a shorter latency in reaching the platform in AAV2/8.CMV.GFP-Sponge-miR-181a/b-injected animals respect to control-injected ones (N≥6 eyes/treatment).",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "(C) Western blot analysis of STAT2 protein levels in mock-, WT-RCMV-E-, ΔE27-RCMV-E- or UV-inactivated RCMV-E-infected REF. 24 h p.i., cells were either left untreated or treated for 5.5 h with DMSO, 2.5 µM MLN4924 for blocking CRL activity or 10 µM MG132 for proteasome inhibition. IE1 and β-tubulin served as infection and loading controls, respectively.",
    "ncbi_link": "E27: 14039086"
  },
  {
    "caption": "(B) 293T cells were transfected with expression plasmids encoding E27-HA or indicated variants. 24 h after transfection, cells were lysed and E27-HA was precipitated using an HA-specific antibody. Precipitates were separated by SDS-PAGE, blotted, and probed using the indicated antibodies.",
    "ncbi_link": "HA: 
E27: 14039086"
  },
  {
    "caption": "(E) 293T cells were transfected with expression plasmids encoding M27-FLAG or the indicated M27-FLAG variants. 24 h after transfection, cells were lysed and M27-FLAG was precipitated using a FLAG-specific antibody. Precipitates were separated by SDS-PAGE, blotted and probed using the indicated antibodies.",
    "ncbi_link": "FLAG: 
M27: "
  },
  {
    "caption": "(G-I) Experimental validation of collective survival. All populations grew to high cell densities in the absence of antibiotics (Blue curves). In the presence of antibiotics, only populations with initial densities greater than NCT grew. NCT was increased with the concentration of antibiotics. Engineered bacteria with the QS-BlaM circuit exhibited a significantly higher NCT than those with the BlaM or the QS-CAT circuits. Carbenicillin was used for the BlaM and QS-BlaM circuits; chloramphenicol for the QS-CAT circuit. Each error bar represents the standard deviation from triplicate measurements.",
    "ncbi_link": "BlaM: 3244915
CAT: 2847485"
  },
  {
    "caption": "(G) Time-lapse images of microbial swarmbot dynamics. The population initiated growth inside the swarmbot and subsequently in the chamber at a high initial density. But no growth occurred for a swarmbot with a low initial density at the same antibiotic concentration (rightmost). The concentration of carbenicillin was 100 µg/ml and the scale bar represents 200 µm.(H) The control strain lacking BlaM circuit. The population could not survive at the same concentration of carbenicillin at the high initial density.",
    "ncbi_link": "BlaM: 3244915"
  },
  {
    "caption": "Figure 6. Experimental control of microbial swarmbot safeguard by other circuits.Demonstration of modular safeguard performance of swarmbots with different collective survival systems. For the swarmbots containing cells carrying the QS-CAT circuit, pulsing flow of medium containing 100µg/ml chloramphenicol established safeguard control but not for the static condition. For the swarmbots with the QS-BlaM circuit, the static condition of 100 µg/ml carbenicillin was sufficient for safeguard control. For all the conditions, safeguard did not occur in the absence of antibiotic (top panels from each condition). All the images were from the swarmbots cultured at 37˚C for 16 hours. The scale bar is 250 µm.",
    "ncbi_link": "BlaM: 3244915
CAT: 2847485"
  },
  {
    "caption": "(B) B-RafE586K signals independently from Ras-GTP, but requires an intact AL. The MEK-ERK activation potential of the indicated HA-tagged B-Raf mutants was assessed by Western blotting using TCLs from transiently transfected Plat-E cells.",
    "ncbi_link": "Ras: 
B-Raf: 673"
  },
  {
    "caption": "(C) B-RafCAAX but not the B-RafV600E oncoprotein signals independently from Ras-GTP, but requires an intact AL. Same experimental set-up as in (B). (D) Quantification of experiments shown in (B) and (C). The signal elicited by the individual reference proteins (B-Rafwt, B-RafE586K, B-RafV600E and B-RafCAAX) was set in each analysis to 100%. n = 3, mean + SEM, t-test, * p < 0.05, ** p < 0.01",
    "ncbi_link": "Ras: 
B-Raf: 673"
  },
  {
    "caption": "(A) Braf-/-;ERTmHRasG12V MEFs were reconstituted with HA-tagged hBRAF constructs or empty vector (EV). Infected cells were either treated with 4-HT (1µM) to induce oncogenic Ras activation or with ethanol (OH) as a control. (B) Quantifications of pMEK (left) and pERK (right) normed to WT level. n = 3, mean + SEM, t-test, ** p < 0.01.",
    "ncbi_link": "Ras: 
Braf: 109880
BRAF: 673
ER: 2100///2099
HRas: 15461"
  },
  {
    "caption": "(C) The AVKA mutation has no discernible influence on Ras-induced paradoxical ERK activation triggered by the D594A mutation. Experimental set-up as in (A), shown are lysates from 4-HT treated MEFs. (D) Quantification of pMEK and pERK levels normed to HA expression. n = 3, mean + SEM, t-test, ** p < 0.01.",
    "ncbi_link": "Ras: 15461"
  },
  {
    "caption": "(E) Top: Braf-/-;ERTmHRasG12V MEFs were reconstituted with the indicated B-Raf constructs. Following induction of Ras signaling, HA-B-Raf proteins were purified using anti-HA antibodies and subject to Western blotting to analyze immunoprecipitation of Raf-1. Bottom: Quantification of co-immunoprecipitated Raf-1 normed to HA-B-Raf levels. n = 3, mean + SEM, t-test, * p < 0.05.",
    "ncbi_link": "B-Raf: 673
Braf: 109880
ER: 2100///2099
HRas: 15461
Ras: 15461"
  },
  {
    "caption": "(C) Southern blot analysis of genomic DNA of parental W4 ES cells, wildtype MEFs and the ES cell clones #286 and #273 (with recombined B-raffloxAVKA allele). Genomic DNA was digested by AseI and analyzed using the external probe indicated in (A).",
    "ncbi_link": "AseI: 
B-raf: 109880"
  },
  {
    "caption": "(D) Genomic PCR showing Cre-mediated recombination of the BraffloxAVKA allele in vivo using the primer pair E14fwd and E15rev (indicated as blue arrows in A).",
    "ncbi_link": "Cre: 
Braf: 109880"
  },
  {
    "caption": "(A) Weight at weaning of BrafAVKA mice from two different founders showed no significant differences. 215: n = WT = 24/ Heterozygous = 32/ AVKA = 19; 273: n = WT = 114/ Heterozygous = 117/ AVKA = 52, mean + SEM, t-test",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(B) Homozygous BrafAVKA mice show reduced splenic cellularity. n = 7, mean + SEM, t-test, * p < 0.05.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(C-E) Relative number of CD8+ T cells. FACS analysis shows an increase in naïve cells (C), whereas differentiated TEM (D) and Tregs (E) reveal a reduction in BrafAVKA mice compared to WT. n = 8, mean + SEM, t-test, * p < 0.05, ** p < 0.01.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(F) Primary B cells of BrafAVKA mice show reduced CD69 surface expression upon LPS and anti-IgM stimulation. n = 3, mean + SEM, test, ** p < 0.01.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(A) Facial appearance of BrafAVKA mice.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(B) Top: In vitro kinase (IVK) assay of B-Raf complexes purified from either WT or BrafAVKA knock-in brains from both founder strains revealed a reduced MEK phosphorylation potential regardless of their purification from NLB or RIPA lysates. Botttom: Quantification of IVK differentials: #215 samples indicated in black, #273 samples in grey.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(C) Western blot analysis showing reduced pMEK and pERK levels in BrafAVKA brains. n = 5, mean + SEM, t-test, ** < 0.01.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(D) Immunohistochemistry showing reduced pERK levels in Purkinje cells of homozygous BrafAVKA mice. Scale bar indicates 10x magnification.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(A) Total brain lysates of WT and BrafAVKA mice were subject to immunoprecipitation (IP) using either anti-B-Raf antibodies or non-specific IgG as negative control. The co-purified proteins were visualized using the indicated antibodies and quantified. Ksr1 is significantly decreased in B-RafAVKA complexes while the other proteins are equally bound to B-RafWT or B-RafAVKA. n = 3, mean + SEM, t-test, * p < 0.05.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "(B) Anti-Myc IP of Plat-E cells transfected with Myc-tagged Raf-1 and different HA-B-Raf constructs. Western blot analysis showed that B-RafAVKA is not impaired in its ability to interact with Raf-1.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(C) Anti-Myc IP of Plat-E cells expressing different Myc- and HA-B-Raf proteins. Note that B-RafAVKA is not impaired in its ability to interact with other B-Raf proteins, while homo-dimerization of B-RafEVKD is enhanced.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(A) MEFs expressing B-RafWT or B-RafAVKA were stimulated with EGF for the indicated time points (min) and analyzed by Western blotting.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(B) IP of EGF stimulated MEFs expressing B-RafWT or B-RafAVKA. Sorafenib was used to increase complex build up.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(C) Proliferation of two different MEF pools expressing either B-RafWT or B-RafAVKA. MEFs expressing B-RafAVKA show a strong reduction in growth rate. n = 3, mean + SEM, t-test, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(D) Cell morphology of B-RafAVKA expressing MEFs are enlarged and present with abnormal nuclei",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(E) MEFs expressing B-RafAVKA show a significant increase in caspase-3 activity. n = 3, mean + SEM, t-test, ** p < 0.01.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(G) Morphology of MEFs expressing B-Rafwt or B-RafAVKA in the presence or absence of TAg.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "(A) MEFs were then infected with retroviral vectors encoding the indicated B-Raf proteins. Giemsa staining revealed transformed and hyper-proliferated cells by dark purple colour. (B) Quantification of Focus formation potential of the B-Raf mutants used in (A). n = 3, mean + SEM, t-test, *** p < 0.001.",
    "ncbi_link": "B-Raf: 109880"
  },
  {
    "caption": "Growth curves of the MCF7 (left) and T47D cells (right) upon gene silencing with siRNAs. siNC: non-targeting siRNA as a negative control, siHN-1: siRNA sequence 1 for HNRNPC, siHN-2: siRNA sequence 2 for HNRNPC, siLMNA: siRNA for LMNA as another negative control. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "HN-1: 3183
HN-2: 3183
HNRNPC: 3183
LMNA: 4000"
  },
  {
    "caption": "Growth curves of the Tet-on Crispr-Cas9-MCF7 (left) and Tet-on Crispr-Cas9-T47D cells (right). Expression of Cas9 was induced with 5uM doxycycline after transfection of the sgRNAs. sgNC: non-targeting sgRNA as a negative control, sgHN-1: sgRNA sequence 1 for HNRNPC, sgHN-2: sgRNA sequence 2 for HNRNPC, sgLMNA: sgRNA for LMNA as another negative control. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "Crispr: 
HN-1: 3183
HN-2: 3183
HNRNPC: 3183
LMNA: 4000
Cas9: 901176"
  },
  {
    "caption": "Relative protein levels of HNRNPC upon CRISPR-mediated gene knock-down, quantified from Western blots of 3 replicates. The error bars represent the ± SD.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "Anchorage independent cell growth assays of the HNRNPC-deficient MCF7 (top) and T47D (bottom) cells.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "Volcano plots showing the differential expression of the genes after HNRNPC knock-down in the MCF7 (A) and T47D (B) cells. The ISGs with significant differential expression were marked as red dots. The cutoffs (dashed line) were set at the log2 fold-change > 1.5 or < -1.5 and the P-value < 0.001.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "qPCR measurements of the expressions of ISGs upon knock-down of HNRNPC in MCF7 and T47D cells using siRNA",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "qPCR measurements of the expressions of ISGs upon knock-down of HNRNPC in MCF7 and T47D cells using CRISPR-Cas9",
    "ncbi_link": "CRISPR: 
HNRNPC: 3183
Cas9: 901176"
  },
  {
    "caption": "11 TFs involved in the interferon response and signaling, which were identified by MARINa as master TFs upon HNRNPC knock-down. In each row, all genes were sorted (from left to right) by their differential expressions in siHNRNPC vs. control cells. The predicted target genes that are positive or negative regulated by the TF are marked as red or blue bars. All the TFs were sorted by the P-values (FDR-corrected) from the MARINa analysis. Ranks of these 11 TFs among all the master TFs identified by MARINa were provided to the right.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "Concentrations of IFNβ, measured by ELISA, in the culturing media of MCF7 and T47D cells 48 hours after siRNA transfections. siNC: non-targeting siRNA as a negative control, siHN-1: siRNA sequence 1 for HNRNPC, siHN-2: siRNA sequence 2 for HNRNPC, siLMNA: siRNA for LMNA as another negative control. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "HN-1: 3183
HN-2: 3183
HNRNPC: 3183
LMNA: 4000"
  },
  {
    "caption": "Growth curves of the MCF7 (D) or T47D cells (E) upon HNRNPC knock-down but with the interferon response blocked with the IFNβ antibody. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "Growth curves of the MCF7 (left) or T47D (right) cells upon HNRNPC knock-down and JAK-STAT inhibition with Ruxolitinib (5uM). Error bars represent mean ± SD. siNC: non-targeting siRNA as a negative control, siHN-1: siRNA sequence 1 for HNRNPC, siHN-2: siRNA sequence 2 for HNRNPC. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "HN-1: 3183
HN-2: 3183
HNRNPC: 3183"
  },
  {
    "caption": "Expression levels of ISGs (A) upon HNRNPC silencing in the cells with lentiviral shRNA-mediated stable knock-down of DDX58 or IFIH1. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "DDX58: 23586
HNRNPC: 3183
IFIH1: 64135"
  },
  {
    "caption": "Expression levels of IFNβ concentration in the media (B) upon HNRNPC silencing in the cells with lentiviral shRNA-mediated stable knock-down of DDX58 or IFIH1. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "DDX58: 23586
HNRNPC: 3183
IFIH1: 64135"
  },
  {
    "caption": "Growth curves of the DDX58- and IFIH1-deficient MCF7 (left) and T47D (right) cells upon HNRNPC knock-down. Each sample has 3 replicates. Error bars represent mean ± SD.",
    "ncbi_link": "DDX58: 23586
HNRNPC: 3183
IFIH1: 64135"
  },
  {
    "caption": "Xenograft tumor models with DDX58-deficient MCF7 cells. Images, weights, and growth records of the xenograft tumor models in female NSG mice established from the DDX58-deficient MCF7 cells upon lentivirus-mediated stable knock-down of LMNA or HNRNPC. Each group has 6 mice. The error bars represent the ± SEM.",
    "ncbi_link": "DDX58: 23586
HNRNPC: 3183
LMNA: 4000"
  },
  {
    "caption": "Xenograft tumor models with DDX58-deficient MCF7 cells. Images, weights, and growth records of the xenograft tumors derived from DDX58-deficient MCF7 cells, which were subjected to periodic siRNA injection, starting from 2 weeks after transplantation of the cells. Each group has 4 mice. The error bars represent the ± SEM.",
    "ncbi_link": "DDX58: 23586"
  },
  {
    "caption": "Immunofluorescence analysis of the dsRNA in MCF7 cells after knock-down of HNRNPC, with 4′,6-diamidino-2-phenylindole (DAPI) staining (blue) and anti-dsRNA antibody J2 (green). Cells transfected with poly I:C was included as a positive control of dsRNA, and the cells treated with RNase III was used as a negative control. siNC: non-targeting siRNA as a negative control, siHN-1: siRNA sequence 1 for HNRNPC, siHN-2: siRNA sequence 2 for HNRNPC. The size of scale bar is 10um.",
    "ncbi_link": "HN-1: 3183
HN-2: 3183
HNRNPC: 3183"
  },
  {
    "caption": "Counts of dsRNA regions in the siNC control cells or in the cells with siHNRNPC, identified in the dsRNA-enriched libraries with anti-dsRNA J2 pull-down or in the control libraries including the IgG control and the input control for dsRNA pull-down. Each bar represents the overlapping dsRNA species from two replicate experiments. Among each set of the dsRNA regions, the dsRNAs from Alus were marked in grey.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "MA plot showing all the dsRNA regions identified in the dsRNA-enriched libraries. For each dsRNA region, mean of the read counts (log2) for two replicates of siHNRNPC and siNC cells was shown on the x-axis, and the average fold change (log2) in siHNRNPC vs. siNC on the y-axis. The up-regulated dsRNA regions were marked in red and down-regulated regions in black.",
    "ncbi_link": "HNRNPC: 3183"
  },
  {
    "caption": "A. Indirect immunofluorescence assays were performed to determine the localization of ectopically expressed PfH3p-HA in ring (R), trophozoite (T) and schizont (S) stages of P. falciparum asexual growth. PfH3p-HA was detected using anti-HA antibodies (green) and endogenous histone H3 with anti-histone H3 N-terminal antibodies (red). DAPI (blue) was used to stain the nucleus. Scale bar = 5 μm.",
    "ncbi_link": "HA: 
PfH3p: 814155///3885798"
  },
  {
    "caption": "B. Nuclei isolated from wild-type (WT) or PfH3p-HA-expressing (WT + PfH3p-HA) schizont stage parasites were treated with 4 U/ml of micrococcal nuclease (MNase) for the indicated amounts of time, the DNA purified and migrated on a 2% agarose gel, and stained with ethidium bromide. Mononucleosomes purified after 10 minutes of MNase treatment were separated using denaturing polyacrylamide gel electrophoresis and either stained with Coomassie Brilliant blue (C.B.) or visualized by immunoblotting with anti-HA (α-HA) or anti-C-terminal histone H3 (α-H3c) antibodies.",
    "ncbi_link": "HA: 
PfH3p: 814155///3885798"
  },
  {
    "caption": "C. Co-immunoprecipitation (IP) experiments of purified mononucleosomes obtained from wild-type (WT) or transfected (WT + PfH3p-HA) schizont stage parasites were performed with either anti-HA antibodies or mouse IgG. Immunoprecipitated products (right panel) were analyzed by immunoblotting using anti-HA or anti-histone H4 antibodies.",
    "ncbi_link": "HA: 
PfH3p: 814155///3885798"
  },
  {
    "caption": "A. Genome-wide distribution of ectopically expressed PfH3p-HA in P. falciparum schizont stages is represented as fold-enrichment of PfH3p-HA ChIP-seq signal over Input (PfH3p-HA / Input in blue; y-axis scale 1-10) or over PfH3n (PfH3p-HA / Input in teal; y-axis scale 1-10) calculated using MACS2. The coverage of PfH3p-HA (red; y-axis scale 0-50), Input (black; y-axis scale 0-30) and PfH3n (green; y-axis scale 0-30) is also shown and represents average reads per million over 1000 nt bins of the genome. The x-axis represents chromosome size in Mb. Major MACS2-derived peaks identified in all replicates are indicated using an orange arrowhead. B. Principal Component Analysis of the different ChIP-seq replicates (bigwig files derived from deduplicated bam files) was performed using the plotPCA function of deepTools on a multibigwig summary file, over 150 nt bins. The Eigen values of the top two principal components PC1 and PC2 are shown and meaningful clustering of replicates highlighted. Rep = Biological Replicate. C. Summary of the PfH3p-enriched peaks - and corresponding genes - identified in the PfH3p-HA versus Input or PfH3p-HA versus PfH3n comparisons using MACS2 peak-calling analysis. The overlap between the two comparisons is indicated using a Venn diagram. FE = Fold Enrichment; q-value represents the Benjamini and Hochberg false discovery rate. D. The genomic context of the six peaks identified in all three PfH3p-HA ChIP-seq replicates is shown. The fold enrichment of PfH3p-HA ChIP-seq signal over Input (PfH3p-HA / Input; blue) or PfH3n (PfH3p-HA / PfH3n; teal) is shown, as are the coverage plots of PfH3p-HA (red), PfH3n (green) and Input (black), which are represented as average reads per million over 1000 nt bins of the genome. DNA replication genes: Replication Protein A 1 (RPA1), Proliferating Cell Nuclear Antigen 1 (PCNA1), Single Stranded DNA binding protein (SSB), Topoisomerase I (TOPO-I), DNA polymerase alpha subunit (DNA pol a), and Topoisomerase II (TOPO-II) are highlighted and their directionality indicated. Note that the data in part D correspond to Biological Replicate 1.",
    "ncbi_link": "HA: 
Replication Protein A 1: 812392
RPA1: 812392
DNA pol a: 812588
DNA polymerase alpha subunit: 812588
Single Stranded DNA binding protein: 812855
SSB: 812855
TOPO-I: 812833
Topoisomerase I: 812833
PfH3p: 814155///3885798
PCNA1: 814288
Proliferating Cell Nuclear Antigen 1: 814288
TOPO-II: 811898
Topoisomerase II: 811898"
  },
  {
    "caption": "(b) Analysis of reaction efficiency for point mutants of the amphipathic helix. GL1 lipidation reactions were run on 400 nm and sonicated liposomes (30 mol% DOPE) with the indicated Atg3 mutants. The extent of GL1-PE formation (top gel) was determined from densitometry and is plotted as percentage of total GL1 (bar graph). The ability to form the Atg3-GL1 conjugate was also assessed for each mutant (bottom immunoblot). Note that this conjugate forms in every case, indicating that no mutant inhibited a step upstream in the reaction. Further, this conjugate specifically accumulates in reactions where lipidation is impaired. In both panels, the samples were prepared at the same time from the same materials and run simultaneously on multiple gels, as indicated by the lines.",
    "ncbi_link": "Atg3: 67841"
  },
  {
    "caption": "(d) Lys 11 represents a tunable node through which curvature dependence of the lipidation reaction can be controlled. Lipidation assays were run as in b. Total GL1 lipidation was assessed from reactions with wild-type Atg3 or mutant forms of Atg3 in which position Lys 11 was changed as indicated. Lipidation efficiency on low PE/low curvature liposomes (30% PE, 400 nm) increases with increasing hydrophobicity of the new amino acid, while liposomes with high PE (55%) or high curvature (sonicated) are good substrates for all active forms of Atg3. Left: Coomassie gels of individual lipidation reactions. Right: densitometry of Coomassie-stained gels revealed the ratio of GL1-PE to the sum of all three GL1 species as in Fig. 2. Light grey bars are sonicated liposomes; dark grey bars are 400 nm extruded liposomes. For b,c, P values were calculated between sonicated and 400 nm samples of the same mutant. For d, P values represent comparison with WT protein on the same liposome size and composition. For all panels, n = 3 independent experiments, error bars represent standard deviation and **P 0.05; *P 0.01. Uncropped gels in Supplementary Fig. 7.",
    "ncbi_link": "Atg3: 67841"
  },
  {
    "caption": "Atg3-knockout MEFs (Atg3−/−) are incapable of forming LC3-II and do not accumulate LC3 puncta. Instead, they accumulate autophagic intermediates that are positive for Atg16. To determine whether the amphipathic helix is critical for in vivo function, Atg3 with wild-type or mutant forms of the amphipathic helix was introduced into Atg3−/− MEFs by lentiviral infection and rescue of the three phenotypes was tested. (a) Immunoblot analysis of LC3-II, GL2-II and GABARAP-II formation. GABARAP lipidation is significantly observed only in the presence of bafilomycin A1 (BafA1: 100 nM). Asterisk indicates a nonspecific band recognized by the Atg3 antibody.",
    "ncbi_link": "Atg3: 67841"
  },
  {
    "caption": "d) Cells as in b were kept in full media before being subjected to fixation and immunolabelling with the anti-Atg16L antibody. Atg16L puncta area as a fraction of total cellular area was obtained as described in Methods. This ratio was plotted as arbitrary units. Grey dashed line indicates the value for Atg3−/− cells rescued with wild-type Atg3. n = 2 (for V15K) or 3 (for all others) independent experiments; the precise n values and number of fields visualized per experiment are listed in the Methods. Raw data can be found in Supplementary Fig. 4. Atg3 variants that support lipidation of LC3 family proteins in vitro (Fig. 5) are indicated with black bars, while those that do not support lipidation are indicated with white bars. P values represent difference from wild-type rescue. **P 0.1; *P 0.05. Error bars in c,d represent s.d. for all samples of n > 2. Uncropped versions of all gels are included in Supplementary Fig. 7.",
    "ncbi_link": "Atg3: 67841"
  },
  {
    "caption": "B, Co-immunoprecipitation (Co-Ip) of TSN and RBP47 in protein extracts prepared from 10-d-old Arabidopsis seedlings expressing Pro35S:GFP-RBP47 and grown under no stress (NS), HS (39ºC for 60 min) or salt (NaCl) stress (150 mM NaCl for 60 min) conditions. The GFP-expressing line was used as a negative control. Endogenous TSN (107 kD) was detected in total fractions (Input) and fractions co-immunoprecipitated (Co-Ip) with RBP47 but not with free GFP in all three conditions. Input and Co-Ip fractions were analyzed by immunoblotting using α-TSN and α-GFP.",
    "ncbi_link": "GFP: 
RBP47: 841384///821447///841157"
  },
  {
    "caption": "D, Localization of GFP-SnRK1α1 and GFP-SnRK1α2 in root cells of 5-d-old Arabidopsis WT and tsn1 tsn2 seedlings grown under 23°C (NS) or incubated at 39°C for 60 min (HS). Insets show enlarged areas inside dashed rectangles. Scale bars = 10 μm.",
    "ncbi_link": "tsn1: 830626
tsn2: 836300"
  },
  {
    "caption": "J, Colocalization of GFP-SnRK1α1, GFP-SnRK1α1CD, or GFP-SnRK1α1RD with RFP-RBP47 in N. benthamiana protoplasts subjected to HS (40 min at 39°C). For colocalization analysis under NS conditions see Fig. EV5B. For CHX treatment, protoplasts were incubated with 200 ng μL-1 CHX for 30 min at 23ºC before HS. GFP and RFP fusion proteins were expressed under the control of the UBQ and 35S promoter, respectively. Scale bars = 5 μm.",
    "ncbi_link": "GFP: 
UBQ: 830705
SnRK1α1: 821259"
  },
  {
    "caption": "E, F, Immunoblot analysis with indicated antibodies of protein extracts prepared from root tips of 10-d-old Arabidopsis tsn1 tsn2 (E) or tsn1 tsn2 expressing ProTSN2:GFP-TSN2 (F) heat-stressed seedlings (39ºC) 0, 20, 40 and 60 min after the onset of HS. The charts show SnRK1 activity, expressed as the ratio of phosphorylated to total SnRK1 protein. The data represent mean ratios of integrated band intensities (for both isoforms) normalized to 0 min ± SD from at least four different experiments. P values denote statistically significant differences for comparisons to 0 min (two-tailed t-test).",
    "ncbi_link": "TSN2: 836300"
  },
  {
    "caption": "G, Expression levels of DIN2 and DIN6 in Arabidopsis WT, tsn1 tsn2, tsn1 tsn2;TSN2 and snrk1α1-/- snrk1α2-/+ 10-d-old heat-stressed seedlings relative to unstressed controls. For CHX treatment, the WT seedlings were pre-treated with 200 ng μL-1 CHX for 30 min before HS. Upper and lower box boundaries represent the first and third quantiles, respectively. Horizontal lines mark the median of five replicate measurements, and whiskers mark the highest and lowest values. Means with different letters are significantly different at P < 0.05 (one-way ANOVA).",
    "ncbi_link": "DIN6: 823888
DIN2: 825184
snrk1α1: 821259
snrk1α2: 822566
tsn1: 830626
tsn2: 836300
TSN2: 836300"
  },
  {
    "caption": "(D, E) Imaging of luciferase activity in the liver of  HIF1aAlbKO (D) and  HIF2aAlbKO (E) mice after a hydrodynamic tail vein injection with a HRE-luc reporter plasmid or control (PBS) according to body weight followed by 6h normoxia or   hypoxia. (F, G) Bioluminescent photon counts normalized to the  PBS control group in liver of (F) HIF1aAlbKO and (G) HIF2aALbKO mice and their wild-type littermates 6h after normoxia  of  hypoxia. Data information: All bars represent mean ± SEM. Each individual data point represent individual mice. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. *** P<0.001; ** P≤ 0.01; * P≤ 0.05. N =  normoxia, H =  hypoxia. Signal around the perimeter of the Petri dishes represent aspecific luciferase signal. ",
    "ncbi_link": "luc: 
Alb: 11657
ALb: 11657
HIF2a: 13819
HIF1a: 15251"
  },
  {
    "caption": "ChIP-seq on liver  derived from  mice which were subjected to hypoxia (6h and 24h), followed by DEX  (10 mg/kg) injection and 2h later sacrificed for liver  isolation. (E) Examples of specific GR  DNA-binding peaks, associated with the DEX-induced gene Slc22a5 in hypoxia (6h and 24h).",
    "ncbi_link": "Slc22a5: 20520"
  },
  {
    "caption": "(F) HIF1aHIF2afl/fl and HIF1aHIF2aAlbKO mice  were put in   hypoxia for 6h and stimulated with DEX. Slc25a30 expression was measured in the liver via RT-qPCR. N=3 per group, one experiment. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ***P<0.001, **P<0.01, *P≤0.05.",
    "ncbi_link": "Alb: 11657
HIF2a: 13819
HIF1a: 15251
Slc25a30: 67554"
  },
  {
    "caption": "(M) HIF1aHIF2afl/fl and HIF1aHIF2aAlbKO mice were put in hypoxia for 6h. Stress GRE genes were measured in the liver via RT-qPCR. N=4 per group, one experiment. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05.",
    "ncbi_link": "Alb: 11657
HIF2a: 13819
HIF1a: 15251"
  },
  {
    "caption": "(D-G)  FFA levels and stress GRE genes were determined in the  plasma  and  iWAT  of female C57BL/6J mice injected with 5 mg  RU486 or vehicle (DMSO) (D, F), and in  GRdim/dim mice  and their wild-type littermates (E, G) after 6h of   normoxia   and hypoxia. N=4-9 per group. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "(H-J)  Blood ketone body  levels 6h after   normoxia and hypoxia  in female C57BL/6J and ADX mice (H), in female C57BL/6J mice injected with 5 mg RU486 or vehicle (DMSO) (I), and in GRdim/dim mice  and their wild-type littermates (J). N=5-9 per group. Data information: All bars represent mean ± SEM. P-values were calculated using two-way ANOVA followed by post-hoc Šídák's multiple comparisons test to correct for multiple testing during the pairwise multiple comparisons, except if otherwise stated. ****P<0.0001, ***P<0.001, **P<0.01, *P≤0.05.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "(G) Atg14F/F (undeleted) or Atg14Δ/Δ (deleted) MEFs were harvested and treated with DSP. * (E) and ** (G) indicate the positions of the immunoglobulin light and heavy chains, respectively. aa, amino acid; DSP, dithiobis(succinimidyl propionate); IP, immunoprecipitation; MEFs, mouse embryonic fibroblasts.",
    "ncbi_link": "Atg14: 100504663"
  },
  {
    "caption": "(A) WT MEFs, Atg16L1 KO MEFs or Atg16L1 KO MEFs stably expressing either full‐length Atg16L1(1-588), Atg16L1(1-230) or Atg16L1Δ(230-300) were cultured in regular DMEM or starvation medium in the presence or absence of 100 nM BafA1 for 2 h. * indicates nonspecific immunoreactive bands.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(B, C) Atg16L1 KO MEFs stably expressing GFP-ULK1 and either full‐length Atg16L1(1-588), Atg16L1(1-230) or Atg16L1Δ(230-300) were cultured in regular DMEM (C) or starvation medium (B,C) for 1 h. Cells were fixed and analysed by immunofluorescence microscopy using anti‐GFP, anti‐Atg16L1 and anti‐LC3 antibodies. Arrowheads indicate the perinuclear localization of Atg16L1(1-230). The number of dots was quantified from more than 30 randomly selected cells from three independent samples as described in the Methods. Data represent mean±s.e. (*P0.001, analysis of variance followed by Bonferroni/Dunn post hoc test). Scale bar, 10 μm, and 2 μm in inset.",
    "ncbi_link": "Atg16L1: 77040
ULK1: 22241"
  },
  {
    "caption": "(D, E) Cells stably expressing GFP-LC3 were cultured in regular DMEM, starvation medium or starvation medium in the presence of 0.2 μM WM or 100 nM BafA1 for 6 h. Total cellular GFP-LC3 signals were analysed by flow cytometry. Representative FACS data were shown (D). The geometric mean of fluorescence intensity was determined. Values are expressed as a percentage of the mean of control cells cultured in regular DMEM. Data represent mean±s.e. (*P0.05) (E). BafA1, bafilomycin A1; GFP, green fluorescent protein; KO, knockout; MEFs, mouse embryonic fibroblasts; NS, not significant; WM, wortmannin; WT, wild‐type.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(A) Atg16L1 KO MEFs stably expressing either full‐length Atg16L1(1-588), Atg16L1(1-230) or Atg16L1Δ(230-300) were cultured in regular DMEM or starvation medium for 1 h. Cells were fixed and subjected to immunofluorescence microscopy using anti‐Atg16L1 antibody. Note that full‐length Atg16L1 and Atg16L1(1-230), but not Atg16L1Δ(230-300), showed punctate structures under starvation conditions (inset).",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(B) FIP200 KO MEFs stably expressing either CFP-Atg16L1(1-588), CFP-Atg16L1(1-230) or CFP-Atg16L1Δ(230-300) were cultured in regular DMEM or starvation medium for 1 h. Cells were fixed and analysed by immunofluorescence microscopy using anti‐GFP antibody. Arrowheads indicate the perinuclear localization of Atg16L1(1-230).",
    "ncbi_link": "Atg16L1: 77040
FIP200: 12421"
  },
  {
    "caption": "(C, D) FIP200 KO MEFs stably expressing CFP-Atg16L1(1-230) were cultured in regular DMEM. Scale bar, 10 μm, and 2 μm in inset.",
    "ncbi_link": "Atg16L1: 77040
FIP200: 12421"
  },
  {
    "caption": "Five upper panels: Northern blots showing the levels of RT3-piRNA, Bmmar6-piRNA, R2Bm-piRNA, and R1Bm-piRNA in normal (Control), Vret-L/S-depleted (Vret KD), Vret-L-depleted (Vret-L KD), and Vret-S-depleted (Vret-S KD) cells. Bantam (miRNA) was detected as a loading control. Two lower panels: western blots showing the efficiency of the Vret knockdown. β-Tub was detected as a loading control.",
    "ncbi_link": "Bantam: 
Bmmar6-piRNA: 
R1Bm-piRNA: 
R2Bm-piRNA: 
RT3-piRNA: 
Vret: 
Vret-L: 
Vret-S: "
  },
  {
    "caption": "Two upper panels: western blots showing the abundances of Flag-Vret-L and Ago3 in both samples. Note that Flag-Vret-L is present only in the Vret-L complex but not with Ago3 isolated from total cell lysates (Fig EV1F). Bottom panel: Northern blot showing the level of PiggyBac-piRNA associated with Ago3 in total lysate (Ago3-IP) and in the Vret-L complex (Flag-Vret-IP). The ratio of the piRNA signal intensity in the two samples is indicated at the bottom.",
    "ncbi_link": "Flag: 
PiggyBac-piRNA: 
Vret-L: "
  },
  {
    "caption": "Two upper panels: western blots showing the abundances of Flag-Vret-L and Siwi in both samples. Bottom panel: Northern blot showing the level of RT3-piRNA associated with Siwi in the total lysate (Siwi-IP) and in the Vret-L complex (Flag-Vret-IP).",
    "ncbi_link": "Flag: 
RT3-piRNA: 
Vret-L: "
  },
  {
    "caption": "Boxplot showing log2 fold-change of Vret-KD (RPM)/Control (RPM) values of piRNAs in increased, unchanged and decreased groups defined by Ago3-KD (RPM)/Control (RPM) values shown in Fig EV1I. Boxplot represents median, first and third quartile, and maximum and minimum values of the log2 fold-change of piRNAs (N = 2). Outliers are represented as open circles.",
    "ncbi_link": "Vret: 
Ago3: 100125337"
  },
  {
    "caption": "Flag-EGFP and -Vret-L WT and mutants were immunoprecipitated using the anti-Flag antibody and then western blotting was performed using anti-Flag, anti-Siwi, anti-Ago3 and anti-Vret antibodies. The domain structures of Tud1mut (Y753A/Y757A/N759A) and Tud2mut (Y973A/ Y976A/N978A) are shown.",
    "ncbi_link": "EGFP: 
Flag: 
Vret-L: "
  },
  {
    "caption": "Immunofluorescence showing the Ago3 signals (green) in control and Vret-depleted BmN4 cells (Vret KD). Vret is shown in red. DAPI shows the nuclei (blue). Scale bar: 10 μm. Immunofluorescence showing the Siwi signals (green) in control and Vret-depleted BmN4 cells (Vret KD). Vret is shown in red. DAPI shows the nuclei (blue). Scale bar: 10 μm.",
    "ncbi_link": "Vret: "
  },
  {
    "caption": "Immunofluorescence showing the Vret signals (red) in control and Ago3-depleted BmN4 cells (Ago3 KD). Ago3 is shown in green. DAPI shows the nuclei (blue). Scale bar: 10 μm. Immunofluorescence showing the Siwi signals (red) in control and Ago3-depleted BmN4 cells (Ago3 KD). Ago3 is shown in green. DAPI shows the nuclei (blue). Scale bar: 10 μm.",
    "ncbi_link": "Ago3: 100125337"
  },
  {
    "caption": "Immunofluorescence showing Flag-Ago3 WT, KA mutant and DDH mutant signals (green) expressed in naïve BmN4 cells (Control). DAPI shows the nuclei (blue). Scale bar: 10 μm. Immunofluorescence showing Flag-Ago3 WT, KA mutant and DDH mutant signals (green) in Ago3-depleted cells (Ago3 KD). DAPI shows the nuclei (blue). Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
Ago3: 100125337"
  },
  {
    "caption": "Immunofluorescence showing the Ago3 signals (green) in control and Siwi-depleted BmN4 cells (Siwi KD). Siwi is shown in red. DAPI shows the nuclei (blue). Scale bar: 10 μm. The three panels on the right-hand side show high magnification images of the part indicated by the white dashed line box in the images on the left-hand side. This panel arrangement applies also for panels B, H and I. Bar chart indicates dot sizes of > 100 Ago3 particles in each case (Large: IntDen value > 106; Small: IntDen value < 106). Immunofluorescence showing the Vret signals (green) in control and Siwi-depleted BmN4 cells (Siwi KD). Siwi is shown in red. DAPI shows the nuclei (blue). Scale bar: 10 μm. Bar chart indicates dot sizes of > 100 Ago3 particles in each case (Large: IntDen value > 105; Small: IntDen value < 105).",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blotting was performed before and after Siwi KD using the anti-Ago3 antibody. Total BmN4 lysate (Total), supernatant (Sup) and pellet (Pellet) fractions upon centrifugation were used.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blotting was performed using the anti-Ago3 antibody on Ago3 immunoisolated from Siwi-depleted cells. Ago3 immunoprecipitated was untreated (−) or treated with phosphatase (+) prior to western botting.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blot showing the degree of phosphorylation of Flag-Ago3 WT and the 8SA mutant in Siwi-depleted cells (Siwi KD).",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blots showing the degree of phosphorylation of Flag-Ago3 WT and its DDH and KA mutants in Siwi-depleted cells (Siwi KD). The second panel from the top corresponds to the top panel with a longer exposure time. Siwi and β-Tub as a loading control were also detected also by western blotting.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blotting was performed using anti-Ago3, anti-Vret and anti-Siwi antibodies on lysates of BmN4 cells before (Control) and after Siwi (Siwi KD) and Siwi/Vret (Siwi/Vret KD) depletion. β-Tub was detected as a loading control.",
    "ncbi_link": "Vret: 
Siwi: 100125336"
  },
  {
    "caption": "Immunofluorescence showing the Flag-Ago3 signals (red) in normal (Control) and Siwi-depleted BmN4 cells (Siwi KD). DAPI shows the nuclei (blue). Scale bar: 10 μm.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Immunofluorescence showing the Flag-Ago3 8SA and 8SE mutant signals (red) in normal (Control) and Siwi-depleted BmN4 cells (Siwi KD). DAPI shows the nuclei (blue). Scale bar: 10 μm.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Western blot showing Ago3 immunopurified from BmN4 cells before (Control) and after Siwi knockdown (Siwi KD). 32P-labeling of RNAs isolated from Ago3 (a mixture of unphosphorylated and phosphorylated) immunopurified from Siwi-depleted cells. 15-20-nt RNAs (indicated by a black line) were isolated and sequenced.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "32P-labeling of RNAs isolated from Ago3. Target-Ss are isolated from Siwi-depleted BmN4 cells but are not isolated from Siwi/Vret double knockdown cells.",
    "ncbi_link": "Vret: 
Siwi: 100125336"
  },
  {
    "caption": "Western blot showing Ago3 immunopurified from BmN4 cells before (Control) and after Siwi knockdown (Siwi KD). Northern blot showing Bmmar6-piRNA precursors in the Ago3 complex. 50-100-nt RNAs (indicated by a black line) were isolated and sequenced.",
    "ncbi_link": "Bmmar6-piRNA: 
Siwi: 100125336"
  },
  {
    "caption": "Immunofluorescence showing the Ago3 signals (green) in Siwi-depleted BmN4 cells (Siwi KD) and Siwi KD cells where Flag-Siwi (red) was expressed. DAPI shows the nuclei (blue). Scale bar: 10 μm. The panels on the right-hand side show high magnification images of the part indicated by the white dashed line box in the images on the left-hand side. This arrangement applies also for panel C. Bar chart indicates dot sizes of > 100 Ago3 particles in each case (Large: IntDen value > 105; Small: IntDen value < 105). A significant difference was found plus/minus Flag-Siwi expression by the Fisher's exact test (P < 0.05).",
    "ncbi_link": "Flag: 
Siwi: 100125336"
  },
  {
    "caption": "Western blots show that the degree of Ago3 phosphorylation was reduced upon Siwi KA mutant as well as Siwi WT and DDH mutant expression.",
    "ncbi_link": "Siwi: 100125336"
  },
  {
    "caption": "Immunofluorescence showing the Ago3 signals (green) in Siwi-depleted BmN4 cells (Siwi KD) and Siwi KD cells where Flag-Siwi KA mutant (red) was expressed. DAPI shows the nuclei (blue). Scale bar: 10 μm. Bar chart indicates dot sizes of > 100 Ago3 particles in each case (Large: IntDen value > 105; Small: IntDen value < 105). A significant difference was found plus/minus Flag-Siwi expression by the Fisher's exact test (P < 0.05).",
    "ncbi_link": "Flag: 
Siwi: 100125336"
  },
  {
    "caption": "(B) Notch  signaling effector Hes5  is expressed high in NSCs  while Eomes  (Tbr2) and Btg2  are expressed high in both NSCs  and BPs  at the mRNA level. Each dot defines the mean and lines define the Standard Deviation (SD). 3-4 biological replicates were collected for each time point.",
    "ncbi_link": "Btg2: 12227
Eomes: 13813
Tbr2: 13813
Hes5: 15208"
  },
  {
    "caption": "(C) Examples of expression  dynamics of  deep layer markers Tbr1, Ctip2  and upper layer  markers Satb2, Cux2  in NSCs, BPs  and NBNs, profiles at population level (left) and single cell level (right). Each dot defines the mean and lines define the SD. 3-4 biological replicates were collected for each time point.",
    "ncbi_link": "Ctip2: 58208
Cux2: 13048
Satb2: 212712
Tbr1: 21375"
  },
  {
    "caption": "(D) Experimental validation of NSCs  isolated at E13.5 using Hes5::GFP  transgenic embryos, showing no detectable protein for Tbr1, Ctip2  and Satb2. NSCs  do express Brn2  (Pou3f2) in vitro and in vivo at protein level. Scale bar = 20μm.",
    "ncbi_link": "GFP: 
Hes5: 15208"
  },
  {
    "caption": "(F) Experimental validation of BPs  isolated at E16.5 using Tbr2::GFP  transgenic embryos, showing no detectable protein for Tbr1, Ctip2  and Satb2. Scale bar = 20μm. (H) Experimental validation of NBNs  isolated at E16.5 using Tbr2::GFP  transgenic embryos, showing  protein expression  for Tbr1, Ctip2, Satb2  and Brn2(Pou3f2). Scale bar = 20μm .",
    "ncbi_link": "GFP: 
Tbr2: 13813"
  },
  {
    "caption": "(B) Expression  profile of selected stem cell  maintenance markers Hes1, Hey1  and Id4. Each dot defines the mean and lines define the SD. 3-4 biological replicates were collected for each  time point. (C) Expression  profile of selected neurogenic  markers Neurog2, Neurod2, and Neurod6. Each dot defines the mean and lines define the SD. 3-4 biological replicates were collected for each time point. (D) Expression  profile of selected gliogenic  markers Olig1, Olig2  and Id1. Each dot defines the mean and lines define the SD. 3-4 biological replicates were collected for each  time point.",
    "ncbi_link": "Hes1: 15205
Hey1: 15213
Id1: 15901
Id4: 15904
Neurod2: 18013
Neurod6: 11922
Neurog2: 11924
Olig1: 50914
Olig2: 50913"
  },
  {
    "caption": "(A) RNAscope fluorescence in-situ hybridization of Ch25h transcripts (red) in the spinal cord of non-immunized mice (NI) (left panels) and mice 17 days after EAE immunization (peak disease) (2 right panels) shown in endothelial cells (Isolectin B4 (IsoB4) green top panels) and activated macrophages/microglia (Ionized calcium biding adaptor molecule 1 (IBA1) green lower panels). Nuclei are shown in blue. (B) Quantitative analysis of Ch25h mRNA expression in the spinal cord of NI and EAE mice comparing expression in macrophages/microglia (MG) and endothelial cells (EC), n = 6 biological replicates/group.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(E) Percentage of eGFP+ CNS ECs in the same condition as in (D). Symbols indicate individual mice and bars indicate mean ± SD. Ch25hfl/fl NI: n = 4 biological replicates, Ch25hfl/fl EAE: n = 5 biological replicates, Ch25hECKO NI: n = 4 biological replicates, Ch25hECKO EAE: n = 4 biological replicates. Representative results of 1 experiment.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(A) EAE disease course in Ch25hECKO and Cre negative littermates (Ch25hfl/fl). Top panel: EAE clinical score. Bars indicate mean ± SEM. Bottom panel: Survival analysis of EAE, depicting disease incidence. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph. (B) As in (A) except that Ch25h fl/fl- Pdgfb-iCreERT2 mice that express Cre recombinase in blood endothelial cells (Ch25hBECKO) are shown. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph. (C) As in (A) except that Ch25hfl/fl- Prox1-CreERT2 mice that express Cre recombinase in lymphatic endothelial cells (Ch25hLECKO) are shown. Representative results of 2 experiments with a minimum of n = 5 biological replicates/group as indicated on the graph.",
    "ncbi_link": "Ch25h: 12642
Cre: 2777477
ERT2: 5595
Pdgfb: 18591
Prox1: 19130"
  },
  {
    "caption": "(D, E) Histopathological quantifications (D) and representatives staining (E) of spinal cord sections of immunized Ch25hfl/fl mice (n = 7 biological replicates) and Ch25hECKO mice (n = 10 biological replicates) at day 21 post-immunization for cellular infiltration (HE). Five sections per mouse were quantified. Scale bars 200 µm (top panels), 100 µm (bottom panels).",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(A) RT-qPCR analysis of Ch25h expression in primary mouse brain microvascular endothelial cells (pMBMECs) isolated from Ch25hfl/fl and Ch25hECKO mice. Cells were left unstimulated (NS) or stimulated with IL-1β. n = 5 biological replicates/group. The experiment was performed 3 times.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(F) RT-qPCR of pMBMECs isolated from Ch25hECKO and Ch25hfl/fl mice and stimulated with IL-1β. n = 4 biological replicates/group. The experiment was realized once.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(G) RT-qPCR of CNS endothelial cells sorted from Ch25hECKO and Ch25hfl/fl mice during EAE (day 10 after immunization). Ch25hECKO n = 3 biological replicates, Ch25hfl/fl n = 4 biological replicates. The experiment was performed once.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(C) 25-OHC, 7-keto-25-OHC, and 24(S)-OHC concentration in the same conditions as in (B). Bars represent mean ± SD. n = 6 biological replicates/group except for Ch25fl/fl IL-1β were n = 5 biological replicates. The experiment was performed once. (D) 25-OHC, 7-keto-25-OHC, and 24(S)-OHC levels in spinal cord tissue extracted from Ch25hfl/fl (n = 8), Ch25hECKO (n = 3) and Ch25hBBBKO (n = 6) at the peak of EAE.",
    "ncbi_link": "Ch25: 12642
Ch25h: 12642"
  },
  {
    "caption": "(H) Percentage (upper left panel) and absolute number (lower left panel) of CNS live cells CD45+CD11b+Ly6CintLy6G+ PMN-MDSC; Percentage of live CD4+CD44+Ki67+ cells (upper right panel) and ratio (lower right panel) of absolute number of PMN-MDSC and proliferating CD4+ T cells in the CNS at the peak of the disease of Ch25hfl/fl (n = 9) and Ch25hECKO mice (n = 8). Symbols depict individual mice and bars indicate mean ± SD. Combined results of 2 independent experiments.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(I) EAE disease course in Ch25hBBBKO mice (n = 11) where the Cre-recombinase is expressed in endothelial cells of the CNS and Cre negative littermates (Ch25hfl/fl: n = 7 and Ch25hfl/wt : n = 2). Bars indicate mean ± SEM. Representative results of 2 independent experiments.",
    "ncbi_link": "Ch25h: 12642
Cre: 2777477"
  },
  {
    "caption": "(B) Survival analysis in the same conditions as in (A). Ch25hfl/fl isotype: n = 7, Ch25hECKO isotype: n = 8, Ch25hfl/fl Combo: n = 8, Ch25hECKO Combo: n = 9.",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(C) Representative contour plots of PMN-MDSC in the CNS at day 22 of EAE assessed by flow cytometry in the same conditions as in (A). (D) As in (C) except that statistical analysis and percentage of PMN-MDSC in live cells are shown. Symbols depict individual mice and bars mean ± SD. Ch25hfl/fl Isotype n = 4, Ch25hECKO isotype n = 4, Ch25hfl/fl Combo, n = 3, Ch25hECKO Combo n = 4. (",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "(E) Representative contour plots of CD101 and representative histograms of Ly6G expression in blood neutrophils at day 16 of EAE assessed by flow cytometry. Ch25hECKO and Ch25hfl/fl mice were treated with isotype or Combo treatment which was initiated at the first symptoms of EAE (day 14 after immunization). (F) As in (E) except that statistical analysis is shown. Symbols depict individual mice, bars mean ± SD. Ch25hfl/lfl isotype n = 7, Ch25hECKO isotype n = 5, Ch25hfl/lfl Combo n = 6, Ch25hECKO Combo n = 5. The experiment was performed once. (",
    "ncbi_link": "Ch25h: 12642"
  },
  {
    "caption": "A IGV browser snapshots showing the distribution of reads around the TSS of the actively transcribed PPM1D gene (chr17:60,587,313-60,643,064; top panel) and of the inactive CD40 gene (chr20:46,114,180-46,129,721; bottom panel) for the indicated histone modifications, input and RNAseq.",
    "ncbi_link": "CD40: 958
PPM1D: 8493"
  },
  {
    "caption": "A H3K122succ levels (detected by immunoblot), relative to the scramble siRNA control, upon depletion of indicated HAT enzyme(s) (GCN5, pCAF, p300 and/or CBP) from MCF7 cells by siRNA. The bar graph shows a representative experiment",
    "ncbi_link": "CBP: 1387
p300: 2033
GCN5: 2648
pCAF: 8850"
  },
  {
    "caption": "B In vitro succinyltransferase assay on recombinant histone octamers as substrate. After incubation with p300 and suc-CoA, the H3K122succ levels were assessed by immunoblot. Ponceau staining of membrane is shown as a loading control.",
    "ncbi_link": "p300: 2033"
  },
  {
    "caption": "F H3K122succ levels in Sirt5-KO cells. Histones were acid extracted from wild type (WT) and Sirt5-KO MEFs and the levels of H3K122succ determined by immunoblot. The level of H3K122succ was normalized to histones extracted from WT MEFs.",
    "ncbi_link": "Sirt5: 68346"
  },
  {
    "caption": "(A) Western Blot for pUb on HeLa control and FBXO7-/- cells after treatment with AO for indicated times.",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "(D) Western Blot for pUb on extracts from day 12 iNeuron control and FBXO7-/- cells after treatment with BafA or AO for indicated times.",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "(A) 3D-SIM images of HeLa control, PINK1-/- and FBXO7-/- cell lines after AO-induced mitophagy. Cells were stained for nuclear DNA (DAPI), mitochondria (HSP60) and pUb. Zoom-ins of regions of interested are enlarged in the middle panel. 3D-surface renderings of insets are shown on the right. Scale bar = 5 µm or 1 µm.",
    "ncbi_link": "FBXO7: 25793
PINK1: 65018"
  },
  {
    "caption": "(D) 3D-SIM images of iN day 12 control, PINK1-/- and FBXO7-/- cell lines after AO-induced mitophagy. Cells were stained for nuclear DNA (DAPI), mitochondria (HSP60) and pUb. Zoom-ins of regions of interest are enlarged in the middle panel. 3D-surface renderings of insets are shown on the right. Scale bar = 5 µm or 1 µm.",
    "ncbi_link": "FBXO7: 25793
PINK1: 65018"
  },
  {
    "caption": "(G) Confocal images of iNeuron d12 Control, PINK1-/- and FBXO7-/- cell lines after AO-induced mitophagy. Cells were stained for nuclear DNA (Hoechst33342), mitochondria (HSP60) and pUb. Scale bar = 10 µm and 5 µm. (H) Evaluation of pUb volume after mitophagy induction. Error bars depict S.D. from three biological replicates. One-way ANOVA with multiple comparisons; p(****)<0.0001.",
    "ncbi_link": "FBXO7: 25793
PINK1: 65018"
  },
  {
    "caption": "(B) Mean Acidic:Neutral mtKeima per-cell ratios measured by flow cytometry for HeLa cells expressing Parkin ndicating the number of hours treated with AO (Antimycin A (5 µM) and Oligomycin (10 µM)) or three hours with 25 nM BafilomycinA (BafA). Error bars depict S.D. from biological triplicate measurements from three independent clones. Two-way ANOVA with multiple comparisons; p(****)<0.0001.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(C) Bar graph showing the number of mtDNA puncta/cell with or without treatment with AO (6 h) in HeLa control or FBXO7-/- cells. Error bars depict S.D. from triplicate technical replicates from two independent clones. One-way ANOVA with multiple comparisons; p(****)<0.0001",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "(A) Workflow for analysis of total protein abundance in HeLa cells expressing Parkin with and without depolarization with AO (16 h). Cell extracts from triplicates were digested with trypsin prior to 18-plex TMT labelling and analysis by mass spectrometry.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(F) PINK1 levels in control cells and in two FBXO7-/- clones were measured by TMT-proteomics in fed cells, from biological triplicates from two independent clones.",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "(B) Log2 FC for the indicated mitochondrial protein-groups in control or FBXO7-/- cells at day 0, 4 or 12 during neurogenesis is shown in violin plots. (C) Log2 FC for the indicated cellular organelle proteins in control or FBXO7-/- cells at day 0, 4 or 12 during neurogenesis is shown in violin plots.",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "(H) Western Blot analysis on HeLa control and FBXO7-/- whole cell lysate, probed for the mitochondrial fission adapter MiD51.",
    "ncbi_link": "FBXO7: 25793"
  },
  {
    "caption": "The gene-expression microarray and RNA-seq data associated with 40 of the breast cancer cell lines were used for the analyses. The panels illustrate the associations of RARα and PPARβ/δ with ATRA sensitivity. The left panels show the basal average levels of the indicated transcript in the cell lines belonging to the T1 and T3 groups (13 cell lines in each of the T1 and T3 groups) defined by ascending ATRA scores. The intermediate and right panels indicate the same results after stratification for the Luminal (microarray and RNA-seq data = 7 cell lines in each of the T1 and T3 groups) and the Basal (microarray and RNA-seq data = 7 cell lines in each of the T1 and T3 groups) phenotype, respectively. fpkm = fragments per kilobase of exon per million fragments mapped.",
    "ncbi_link": "PPARβ/δ: 5467
RARα: 5914"
  },
  {
    "caption": "Basal levels of RARα, RARβ, and RARγ mRNA splicing variants in mammary tumorsTotal RNA was extracted from the tissue slices deriving from the surgical specimens of breast cancer patients used in Fig3 before any treatment with DMSO or ATRA. RNA was subjected to RT-PCR analysis to determine the basal expression of the indicated RAR splicing variants.Each value represents the mean ± SD of two replicate measurements. The table shows the statistical significance of the indicated comparisons. *Significantly different (P-value < 0.05, Student's t-test). **Significantly different (P-value < 0.01, Student's t-test).",
    "ncbi_link": "RARα: 5914
RARβ: 5915
RARγ: 5916"
  },
  {
    "caption": "The plots show the correlation curves between the levels of the indicated RARα-variant transcripts and the RARα protein.",
    "ncbi_link": "RARα: 5914"
  },
  {
    "caption": "Effects of RAR agonists on the growth of Luminal and Basal breast cancer cell linesThe indicated Luminal and Basal cell lines were challenged with increasing concentrations of ATRA, the RARα agonist, AM580, the RARβ agonist, UVI2003, and the RARγ agonist, BMS961, for 6 days. The complement of RAR-variant transcripts expressed in each cell line is shown in the left bar graphs (mean ± SD of two replicate measurements). The growth curves (sulforhodamine assay) of the cell lines are illustrated by the right linear plots. The results are expressed in % values relative to the corresponding control dishes treated with vehicle alone (right graphs). Each result is the mean ± SD of five replicate wells. ATRA sc = ATRA score.",
    "ncbi_link": "RARα: 5914
RARβ: 5915
RARγ: 5916"
  },
  {
    "caption": "A RARα1/3 plasmid construct and the corresponding control void vector were stably transfected into ATRA-resistantMDA-MB453 cells. Two cell clones over-expressing RARα (RARA-C5 andRARA-C7) and two appropriate control clones (Vect-C1 andVect-C2) were isolated. A RARα3 shRNA plasmid construct and the corresponding void vector were stably transfected into ATRA-sensitiveSKBR3 cells. After selection, two cell clones silenced for RARα3 (RARA-sh18 andRARA-sh19) and two appropriate control clones (Vect-C6 andVect-C8) were isolated.A, D The indicated clones and the parental cell line (WT) were transiently transfected with the RARE-DR5-Lucretinoid reporter construct and the level of luciferase activity was measured 24 h after treatment with vehicle (DMSO) and ATRA (100 nM), as illustrated in the upper bar graph. Each value is the mean ± SD of three replicate cultures. The levels of the RARα protein measured in the indicated clones by Western blotanalysis is shown under the bar graph. To demonstrate that similar levels of total proteins were loaded in each lane, the β-actin band signal obtained after re-blotting of the gel is shown. FI = Fluorescence intensity.",
    "ncbi_link": "RARA: 5914
RARα: 5914"
  },
  {
    "caption": "A, D The indicated clones and the parental cell line (WT) were transiently transfected with the RARE-DR5-Lucretinoid reporter construct and the level of luciferase activity was measured 24 h after treatment with vehicle (DMSO) and ATRA (100 nM), as illustrated in the upper bar graph. Each value is the mean ± SD of three replicate cultures. The levels of the RARαprotein measured in the indicated clones by Western blotanalysis is shown under the bar graph. To demonstrate that similar levels of total proteins were loaded in each lane, the β-actin band signal obtained after re-blotting of the gel is shown. FI = Fluorescence intensity.B, E The panels illustrate the growth curves of the indicated MDA-MB453 and SKBR3 clones and the SKBR3 parental cell lines (WT) measured with the sulforhodamine assay.C The bar graphs illustrate the effect of increasing concentrations of ATRA on the growth of the indicated MDA-MB453 clones and the parental cell line. The cell lines were challenged with vehicle (DMSO) or ATRA for 3, 6, and 9 days prior to the sulforhodamine assay. OD = optical density at 540 nm. Each value is the mean ± SD of five replicate culture wells.",
    "ncbi_link": "RARE: "
  },
  {
    "caption": "A. Representative immunofluorescence images and quantifications showing that 3 months old Hnf1apKO mice have increased number of KI67+ (red) acinar cell nuclei co-staining with DAPI (blue) and Amylase (green). Arrows point to KI67+ acinar cells in Hnf1apKO mouse. Scale bar is 200 μm. Acinar proliferation is represented as the average of the KI67+/Amylase+ cell ratio. Quantifications were performed on 3 random fields from 3 Pdx1Cre and 3 Hnf1apKO mice. P-values are from two-tailed Student's t test.",
    "ncbi_link": "Cre: 2777477
Hnf1a: 21405
Pdx1: 18609"
  },
  {
    "caption": "Representative H&E stainings of pancreata from KrasG12D and Hnf1apKO;KrasG12D mice. B-D. KrasG12D and Hnf1apKO;KrasG12D mice have normal morphology at 7 days. E-J. At 21 days Hnf1apKO;KrasG12D mice show acinar-to-ductal metaplasia (dashed encircled areas) and regions with desmoplastic reaction (asterisk), which are not observed in KrasG12D mice (E, H). K-P. At 8 weeks KrasG12D pancreas show occasional abnormal ductal structures (dashed encircled areas in N which is a magnification of squared dotted box in K) and Hnf1apKO;KrasG12D mice (L,M,O,P) present mucinous tubular complexes (black arrows), and more advanced PanINs with luminal budding (open arrows) including foci of spindle cell proliferation (asterisks) and incipient infiltrative growth (black dashed box area in O). Data information: Black dashed boxes in (E,F, K, L and O) indicate magnified areas in (H, G, N, M and P) respectively. Scale bars indicate 100 µm (C,E,F,K,L), 50 µm (O) and 20 µm (B,D,G,H-J,M,N,P).",
    "ncbi_link": "Hnf1a: 21405
Kras: 16653"
  },
  {
    "caption": "A. Fold change (FC) in transcripts in Hnf1aaKO vs. control pancreas, plotted against significance (-Log10 q; genes significant at q<0.05 are shown as colored dots above the horizontal line).",
    "ncbi_link": "Hnf1a: 21405"
  },
  {
    "caption": "B. GSEA showing that genes specific to differentiated acinar cells were downregulated in Hnf1aaKO pancreas, but not genes specific to islets or duct cells. Upregulated genes were enriched in genes specific to mesenchymal cells. Lineage-enriched genes were obtained from Muraro et al. (Muraro et al., 2016).",
    "ncbi_link": "Hnf1a: 21405"
  },
  {
    "caption": "D. GSEA revealed that Hnf1aaKO pancreas showed increased transcripts involved in oncogenic pathways such as EMT, MAPK, KRAS, PI3K-AKT.",
    "ncbi_link": "Hnf1a: 21405"
  },
  {
    "caption": "E. HNF1A promotes transcriptional activation of direct target genes. Left: HNF1A bound-genes were enriched among genes that showed downregulation in Hnf1a mutants, but not among upregulated genes. P-values and odds ratios (O.R.) calculated by Fisher's exact test. Right: Venn diagrams showing overlap of HNF1A-bound genes with genes that were downregulated and upregulated in Hnf1a mutant pancreas.",
    "ncbi_link": "Hnf1a: 21405
HNF1A: 21405"
  },
  {
    "caption": "A. Human orthologs of genes that were up- and down-regulated in Hnf1aaKO pancreas were also up- and down-regulated in human pancreas with low vs. high HNF1A expression (lowest vs. highest expression deciles, respectively). A random list of 717 genes controlled for similar expression levels was used for comparison. Violin plots include median and interquartile ranges. Dots are average values for each gene. Kruskall Wallis P<0.0001.",
    "ncbi_link": "Hnf1a: 21405
HNF1A: 6927"
  },
  {
    "caption": "D. HNF1A mRNA levels differed in HNF1A LoF and control groups (Kruskal-Wallis, P<0.01), despite considerable variability and overlap between groups. E. KDM6A mRNA levels were downregulated in HNF1A LoF tumors (Kruskal-Wallis, P<0.001).Data information: Box plots in (D and E) show HNF1A and KDM6A expression in HNF1A LoF tumors (n=26) and Control 1 (n=39) and Control 2 (n=57) tumors. The horizontal central line marks the median. Box limits indicate the first and third quartiles and whiskers extend to highest and lowest data points within 1.5 x interquartile range outside box limits.",
    "ncbi_link": "HNF1A: 21405
KDM6A: 22289"
  },
  {
    "caption": "H&E staining of pancreata from Kdm6apKO;KrasG12D and KrasG12D mice. A-C. 7 day-old KrasG12D and Kdm6apKO;KrasG12D mice showed normal morphology. D-I. At 21 days, KrasG12D mice showed normal pancreas morphology (dotted area at in D is shown at large magnification in G) whereas Kdm6apKO;KrasG12D mice already show acinar-to-ductal metaplasia (dashed encircled area in F), spindle cell proliferation (asterisks in E and H), sarcomatoid architecture (I) and desmoplastic reaction (black arrowhead in H). J-O. KrasG12D mice present occasional acinar-to-ductal metaplasia and low grade PanINs at 8 weeks (M is a magnification of squared dotted box in J and see Fig 1N) whereas at the same age pancreas from Kdm6apKO;KrasG12D mice show massive remodeling (K), extensive acinar-to-ductal metaplasia (L and dashed encircled area in N), cancer with prominent spindle/mesenchymal proliferation, infiltrative growth (black arrows and asterisk respectively in O) and abundant stroma (black arrowheads in N). Data information: Scale bars: 100 µm (B,D,E,J,K) or 20 µm (A,C,F-I, L-N). ",
    "ncbi_link": "Kdm6a: 22289
Kras: 16653"
  },
  {
    "caption": "A. Fold change (FC) and significance for transcripts in Kdm6apKO vs. control pancreas. Genes significant at q<0.05 are shown as colored dots above the horizontal line.",
    "ncbi_link": "Kdm6a: 22289"
  },
  {
    "caption": "B. GSEA showing that genes specific to differentiated acinar cells were downregulated in KDM6A-deficient pancreas, but not genes specific to islets or duct cells. Upregulated genes were enriched in genes specific to mesenchymal cells. Lineage-enriched genes were obtained from (Muraro et al., 2016).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "D. GSEA showed increased expression of indicated oncogenic pathway genes in Kdm6apKO pancreas.",
    "ncbi_link": "Kdm6a: 22289"
  },
  {
    "caption": "E. KDM6A functions as a transcriptional activator of direct target genes in pancreatic cells. Left: Downregulated, but not upregulated, genes in Kdm6apKO pancreas were enriched for KDM6A binding. P-values and odds ratios (O.R.) were calculated by Fisher's exact test. Right: Venn diagrams showing overlap of down and upregulated genes with KDM6A binding.",
    "ncbi_link": "KDM6A: 22289
Kdm6a: 22289"
  },
  {
    "caption": "F. KDM6A-bound enhancers and promoters showed increased H3K27me3 and decreased H3K27ac in Kdm6apKO pancreas.",
    "ncbi_link": "KDM6A: 22289
Kdm6a: 22289"
  },
  {
    "caption": "G. Genes that were downregulated in Kdm6apKO pancreas (KDM6A-dependent genes) showed greatest changes in histone marks. Box plots show fold-changes of H3K27me3 (left) and H3K27ac (right) signals in Kdm6apKO compared to control. Signals were analyzed in KDM6A bound regions in promoters and enhancers of genes that were KDM6A dependent (grey; n=420 regions) and independent (white; n=8035 regions). The signals are average values from ChIP-seq experiments in two biological replicates. The horizontal central line marks the median. Box limits indicate the first and third quartiles and whiskers extend to highest and lowest data points within 1.5 x IQR outside box limits. P-values were determined by two-tailed Mann-Whitney U test.",
    "ncbi_link": "Kdm6a: 22289
KDM6A: 22289"
  },
  {
    "caption": "H. Changes in KDM6A, H3K27me3 and H3K27ac ChIP-seq profiles in the Ppp4r4-Serpina10 locus in Kdm6apKO pancreas.",
    "ncbi_link": "H3: 15268///319148
KDM6A: 22289
Kdm6a: 22289
Ppp4r4: 74521
Serpina10: 217847"
  },
  {
    "caption": "I. qPCR of H3K27me3, H3K27ac and H3K4me1 changes in promoter and enhancer regions highlighted in (H) (R1, R2, R3), and Serpin10 mRNA. Error bars show +/-SD and P-values are from two-tailed Student's t test, n=3.",
    "ncbi_link": "H3: 15268///319148
Serpin10: 217847"
  },
  {
    "caption": "J. KDM6A-bound genes that showed decreased expression in Kdm6apKO pancreas (functional KDM6A binding sites) showed simultaneous gain of H3K27me3 and loss and of H3K27ac.",
    "ncbi_link": "H3: 15268///319148
KDM6A: 22289
Kdm6a: 22289"
  },
  {
    "caption": "B. Co-binding analysis in functional KDM6A-bound enhancer and promoter regions revealed that HNF1A was the most enriched co-bound TF amongst three other acinar cell TFs. Binding regions of TAL1 in a non-pancreatic cell type and random binding sites were used as negative controls. P-values was determined by Fisher's exact test for peak comparisons using all enhancer and promoter regions as background.",
    "ncbi_link": "HNF1A: 21405
KDM6A: 22289
TAL1: 21349"
  },
  {
    "caption": "C. The most downregulated genes in Kdm6apKO pancreas are shown ranked by q-value, and are almost invariably bound by HNF1A and down regulated in Hnf1aaKO pancreas, or known to be direct HNF1A-dependent target genes from other studies (red and purple, respectively).",
    "ncbi_link": "HNF1A: 21405
Hnf1a: 21405
Kdm6a: 22289"
  },
  {
    "caption": "D,E. GSEA analysis on the Hnf1aaKO and Kdm6apKO ranked-ordered gene lists vs. their reciprocal up- or downregulated gene sets, demonstrated that KDM6A and HNF1A regulate similar genes.",
    "ncbi_link": "Hnf1a: 21405
HNF1A: 21405
Kdm6a: 22289
KDM6A: 22289"
  },
  {
    "caption": "F. Expression changes in Hnf1aaKO and Kdm6apKO pancreas, showing that genes bound by KDM6A and downregulated in Kdm6apKO pancreas (red dots) were generally downregulated in Hnf1aaKO pancreas.",
    "ncbi_link": "Hnf1a: 21405
Kdm6a: 22289
KDM6A: 22289"
  },
  {
    "caption": "G. HNF1A and KDM6A co-occupy the same regions in Pah, which is downregulated in Hnf1a and Kdm6a knock-out pancreas.",
    "ncbi_link": "HNF1A: 21405
Hnf1a: 21405
KDM6A: 22289
Kdm6a: 22289
Pah: 18478"
  },
  {
    "caption": "H. Genes that were co-bound by KDM6A and HNF1A showed greatest downregulation in Kdm6apKO pancreas, compared with KDM6A-bound genes that were not bound by HNF1A. Box plots show median and IQR of Log2 TPM fold-changes and whiskers extend to highest and lowest data points within 1.5 x IQR outside box limits. P-values were determined by two-tailed Student's t tests and n=4 replicates per condition.",
    "ncbi_link": "HNF1A: 21405
KDM6A: 22289
Kdm6a: 22289"
  },
  {
    "caption": "B. Western blot showing loss of HNF1A and unchanged KDM6A in Hnf1a-/- pancreas.",
    "ncbi_link": "Hnf1a: 21405"
  },
  {
    "caption": "C. Differential binding analysis of KDM6A in Hnf1a-/- vs. wild type pancreas. Pink dots below zero (1873 sites) show regions with reduced KDM6A binding and pink dots above zero (118 sites) are regions with increased binding at FDR<0.05.",
    "ncbi_link": "Hnf1a: 21405
KDM6A: 22289"
  },
  {
    "caption": "Regions that show reduced KDM6A binding in Hnf1a-/- chromatin are strongly bound by HNF1A and are highly enriched in HNF1 motifs. P-values in (D) were calculated with two-tailed Mann-Whitney U test",
    "ncbi_link": "HNF1: 21405
Hnf1a: 21405
HNF1A: 21405
KDM6A: 22289"
  },
  {
    "caption": "Regions that show reduced KDM6A binding in Hnf1a-/- chromatin are strongly bound by HNF1A and are highly enriched in HNF1 motifs. P-values in (E) with Fisher's exact test.",
    "ncbi_link": "Hnf1a: 21405
HNF1: 21405
HNF1A: 21405
KDM6A: 22289"
  },
  {
    "caption": "F. KDM6A binding is markedly reduced in HNF1A and KDM6A co-bound regions in Hnf1a-/- pancreas, but not in other KDM6A bound regions.",
    "ncbi_link": "Hnf1a: 21405
HNF1A: 21405
KDM6A: 22289"
  },
  {
    "caption": "G. Genes that loose KDM6A binding in Hnf1a-mutant pancreas are predominantly downregulated in Hnf1aaKO pancreas and are direct HNF1A target genes (red dots).",
    "ncbi_link": "Hnf1a: 21405
HNF1A: 21405
KDM6A: 22289"
  },
  {
    "caption": "A Western blot analysis of B16F1 WT and two independent XIAPKO cell lines. Actin was used as a loading control.",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "B Subcutaneous melanoma tumour growth in BL/6 WT mice (n=5) using B16F1 WT and XIAPKO (clone1 and 2).",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "C Representative H&E (scale bar 50 µm) and fluorescent images of cl-Caspase 3 staining in B16 WT and XIAPKO tumours. Nuclei were stained with DAPI (blue). Scale bar 100 µm. Quantification thereof (right panel). The average of cl-Caspase 3 positive cells from 5 randomly selected areas of the tumour (5 mice per genotype) was represented. Dots represent individual mice (n=5).",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "D qRT-PCR analysis (PrimePCRTM Assay) of different cyto-/chemokines in B16F1 WT cells plotted vs B16F1-XIAPKO cells (clone1 and 2). Samples that are at least 2-fold up-regulated are shown in red, samples that are at least 2-fold down-regulated are shown in green.",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "E IL8 measurement in the supernatant of the indicated cell lines after 48 h transfection with siScr (control) or siXIAP and Western blot analysis of the corresponding cell lysates (bottom).",
    "ncbi_link": "XIAP: 442989"
  },
  {
    "caption": "G qRT-PCR analysis (PrimePCRTM Assay) of different cyto-/chemokines in HEK293T cells overexpressing myc-XIAP plotted vs HEK293T cells overexpressing myc-XIAPΔRING. Samples that are at least 2-fold up-regulated are shown in red, samples that are at least 2-fold down-regulated are shown in green.",
    "ncbi_link": "myc: 
XIAP: 331"
  },
  {
    "caption": "H Human cytokines array analysis of HEK293T cells transfected with myc-XIAP or myc-XIAPΔRING. Medium was changed after 16 h and the supernatant was collected after 48 h. Pre-spotted nitrocellulose membranes were incubated with the supernatants overnight at 4°C.",
    "ncbi_link": "myc: 
XIAP: 331"
  },
  {
    "caption": "A Western blot analysis of cell lysates of BLM and BLM-XIAPKO cells (input) and XIAP-IP. Data are representative of two experiments.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "D Western blot analysis of cell lysates of BLM, BLM-XIAPKO, SK-Mel28, SK-Mel28-XIAPKO, B16, and B16-XIAPKO cells (input) and RIPK2-IP. Poly-ubiquitin is detected using anti-ubiquitin antibody.",
    "ncbi_link": "XIAP: 331
XIAP: 11798"
  },
  {
    "caption": "E IL8 measurement in the supernatant of transfected BLM (left panel) or SK-Mel28 (right panel) cells with siScr (control), siXIAP, siTAB1 or siRIPK2 after 48 h. Western blot analysis of the respective cell lysates of BLM cells (left bottom) or SK-Mel28 cells (right bottom) transfected with the indicated siRNA.",
    "ncbi_link": "RIPK2: 8767
TAB1: 10454
XIAP: 331"
  },
  {
    "caption": "B Representative IF (neutrophils staining) in B16F1 WT, XIAPKO, TAB1KO or RIPK2KO tumours (Scale bar 50 µm) and quantification of Ly6G+ cells. The sum of Ly6G-positive cells from 5 randomly selected areas of the tumour (5 mice per genotype) was represented. Dots represent individual mice (n=5). C B16F1 WT, XIAPKO (clone 2) subcutaneous melanoma tumour growth in BL/6 WT mice (n=5). Mice were intra-peritoneal injected with IgG antibody as a negative control or Ly6G antibody 1 day prior to the subcutaneous injection of the B16F1 WT or XIAPKO cells.",
    "ncbi_link": "RIPK2: 192656
TAB1: 66513
XIAP: 11798"
  },
  {
    "caption": "A) Shear-dilation relations of Tek-Cre::Lama5-/- and Lama4-/- mesenteric resistance arteries and corresponding wild type controls show a reduced response of Tek-Cre::Lama5-/- arteries and an enhanced response of Lama4-/- arteries. Data shown are mean changes in vessel diameter (Δ µm) ± s.e.m. from 8 experiments with 16 wild type and 16 KO arteries; KO and wild type were analysed as pairs in each experiment. **P<0.01, paired t-test.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "The dose-response curves of arteries from wild type, Tek-Cre::Lama5-/- (B) and Lama4-/- mice (C) and wild type littermates stimulated with methacholine do not show significant differences (n.s.). Data are expressed as percent relaxation of the maximum force developed in presence of 0.3 µM U46619, and are mean values ± s.e.m from 7 experiments with 1 wild type and 1 KO artery in each experiment.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "A) Three-dimensional digital reconstructions of optical sections through immunofluorescently stained mesenteric resistance arteries from wild type, Tek-Cre::Lama5-/- and Lama4-/- mice, and optical sections through vessel walls to show the endothelial and underlying smooth muscle layers. DAPI staining permits identification of endothelial cell nuclei, which lie perpendicular to the nuclei of the smooth muscle cells. Laminin α5 is absent from endothelial basement membranes of Tek-Cre::Lama5-/- arteries (arrow) but is still present in smooth muscle basement membranes (asterisk), while laminin α4 is still detectable in both endothelial and smooth muscle basement membranes. Lama4-/- arteries lack laminin α4 in both endothelial (arrow) and smooth muscle (asterisk) basement membranes, but laminin α5 is still detectable. Scale bars are 10 μm.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "B) Scanning electron microscopy images of endothelial cell-denuded mesenteric resistance arteries show a comparable topography of the endothelial basement membrane in wild type, Tek-Cre::Lama5-/- and Lama4-/- arteries. The arrows indicate artificial ruptures due to preparation procedure. Scale bars are 100 nm.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "C) Intravital microscopic quantification of mesenteric arteries sizes in vivo show smaller diameters (-24.3%) in Tek-Cre::Lama5-/- arteries and larger diameters (+27.6%) in Lama4-/- arteries compared to wild type controls. Auto-fluorescence of the internal elastic lamina allowed a good approximation of mesenteric arteries lumen diameter. Scale bar is 100 µm. Data are means ± s.e.m from a minimum of 4 first order mesenteric arteries imaged at least in 4 mice per genotype. * P<0.05 unpaired t-test.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "B) Enhanced fold change (Δ) in COX2 mRNA expression in HUAECs plated on laminin 511 versus laminin 111 in response to shear. mRNA data are means ± s.e.m of 4 independent experiments with triplicates/ experiment, paired t-test.",
    "ncbi_link": "COX2: 4513"
  },
  {
    "caption": "B) Vinculin immunofluorescence staining of whole mount wild type, Tek-Cre::Lama5-/- and Lama4-/- mice mesenteric resistance arteries reveal smaller adhesion complexes in Tek-Cre::Lama5-/- (arrow heads) and larger adhesion complexes in Lama4-/- vessels (arrow heads). Scale bar is 10 µm. Data are means ± s.e.m from 300 cells from 9 wild type and 9 KO arteries isolated from 3 mice/genotype. ***P<0.001, ****P<0.0001, unpaired t-test.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "B) Vinculin immunofluorescence staining of whole mount wild type, Tek-Cre::Lama5-/- and Lama4-/- mice mesenteric resistance arteries reveal smaller adhesion complexes in Tek-Cre::Lama5-/- (arrow heads) and larger adhesion complexes in Lama4-/- vessels (arrow heads). Scale bar is 10 µm. Correpsonding quantification of sizes (C) and frequency distribution (D) of adhesion complexes per endothelial cell. Data are means ± s.e.m from 300 cells from 9 wild type and 9 KO arteries isolated from 3 mice/genotype. ***P<0.001, ****P<0.0001, unpaired t-test.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "E, F) The endothelium of excised wild type, Tek-Cre::Lama5-/- aortae were analysed by AFM, revealing reduced cortical stiffness in Tek-Cre::Lama5-/- vessels (-9.5%). Data are means ± s.e.m from 4 experiments employing 4 KO arteries and 4 wild type controls in each experiment. *P<0.05, ****P<0.0001, unpaired t-test.",
    "ncbi_link": "Cre: 
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "E, F) The endothelium of excised wild type and Lama4-/- aortae were analysed by AFM, revealing increased cortical stiffness in Lama4-/- vessels (+2%). Data are means ± s.e.m from 4 experiments employing 4 KO arteries and 4 wild type controls in each experiment. *P<0.05, ****P<0.0001, unpaired t-test.",
    "ncbi_link": "Lama4: 16775"
  },
  {
    "caption": "A) Double immunofluorescence staining for phosphorylated myosin light chain II (pMLC II) and VE-cadherin in mesenteric resistance artery endothelium from wild type, Tek-Cre::Lama5-/- and Lama4-/- mice (arrow heads). Scale bar is 10µm. B) Quantification of the pMLC II signal along VE-cadherin signal revealed significantly less overlap in Tek-Cre::Lama5-/- and more overlap in Lama4-/- endothelium, compared with wild type controls. The data are normalized to the skeletal length of the VE-cadherin signal. Values shown are means ± s.e.m resulting from quantification of 4 field of view per arteries, 4 mice /genotype. *P<0.05, **P<0.01, paired t-test.",
    "ncbi_link": "Cre: 
Lama4: 16775
Lama5: 16776
Tek: 21687"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3 (A) GFP+ Ghost X4R5 cells obtained after treatment with supernatant from infected SERINC3 KD cells. Results are expressed as a ratio to the number of GFP+ cells after treatment with supernatant from infected control cells. . Mean ± SD of three independent experiments is shown.",
    "ncbi_link": "luciferase: 116160065
SERINC3: 10955"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3, followed or not by infection with NL4-3 EGFP-Nef+ HIV-1 (red boxes). (B) Number of particles secreted were quantified by NTA. Results are expressed as a ratio to the number of particles secreted by uninfected luciferase shRNA cells.",
    "ncbi_link": "EGFP: 
luciferase: 116160065
Nef: 156110
SERINC3: 10955"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3, followed or not by infection with NL4-3 EGFP-Nef+ HIV-1 (red boxes). (C) 100K pellets from infected cells were subjected to iodixanol velocity gradient separation. Six fractions were recovered and analyzed by Western blot for the presence of SPN, SERINC3 and p24. (T = top; B = bottom). (D) Quantification of SPN and p24 signals in the different fractions of two independent iodixanol fractionations (exp 1: open symbols, exp 2: closed symbols). AU = band intensity in a given pellet / sum (band intensity in all 12 pellets). ",
    "ncbi_link": "EGFP: 
luciferase: 116160065
Nef: 156110
SERINC3: 10955"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3, followed or not by infection with NL4-3 EGFP-Nef+ HIV-1 (red boxes). 2K, 10K, 100K obtained from CCM of control cells and SERINC3 KD cells either uninfected of infected with NL4-3 EGFP-Nef+ were analyzed by Western blot with antibodies against SPN, and p24. The 2K, 10K, and 100K pellets obtained from 20 x 106 cells were loaded on the gel. Representative images (E)",
    "ncbi_link": "EGFP: 
luciferase: 116160065
Nef: 156110
SERINC3: 10955"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3, followed or not by infection with NL4-3 EGFP-Nef+ HIV-1 (red boxes). 2K, 10K, 100K from CCM of control cells and SERINC3 KD cells either uninfected of infected with NL4-3 EGFP-Nef+ were analyzed and quantification of SPN and p24 signals (F) are shown. For each pellet, arbitrary units (AU) represent the ratio of signal intensity in the given pellet to the total amount of protein in the same given pellet and relative to the total amount in 2K+10K+100K from control cells.",
    "ncbi_link": "EGFP: 
luciferase: 116160065
Nef: 156110
SERINC3: 10955"
  },
  {
    "caption": "Jurkat cells were infected with lentivirus expressing control luciferase shRNA or shRNAs targeting SERINC3, followed or not by infection with NL4-3 EGFP-Nef+ HIV-1 (red boxes). (G) Multiplex bead-based flow cytometry assay for detection of EV surface markers. Antibody-coated capture beads were incubated with EV samples. Captured EVs were detected with a mixture of APC-labeled anti-CD9, anti-CD63, and anti-CD81. Quantification of the median APC fluorescence values for all bead populations after background and isotype antibody correction. Results were relativized to the values obtained with control sample for each experiment. Dotted line represents values obtained for EVs isolated from control cell CM.",
    "ncbi_link": "EGFP: 
luciferase: 116160065
Nef: 156110
SERINC3: 10955"
  },
  {
    "caption": " The SnRK2 OST1 activates ABFs for expression of a luciferase reporter (LUC) in yeast. Luciferase activity is given on a Log10 scale as relative counts of light emission per second (rcps) normalized to the cell density. The OST1-mediated induction factor is indicated above the columns. In the absence of ABFs, the LUC activity was 3 x 103 rcps. ",
    "ncbi_link": "LUC: 
OST1: 829541"
  },
  {
    "caption": " Combining the ABA signaling components ABF2, OST1, the PP2C ABI1, and RCAR11 provides ABA-controlled LUC expression. The reporter is under the control of a minimal promoter that contains ABA-responsive cis elements (ABREs). Core ABA signaling involves the RCAR receptor that inhibits the ABA coreceptor (PP2C) in the presence of ABA and allows the activation of the protein kinase SnRK2. SnRK2 phosphorylates and activates the key transcription factor ABF, which targets promoters containing ABRE. Reporter activity was determined 16 h after exogenous ABA (0.1 mM) administration and referred to samples expressing ABF2 alone. ",
    "ncbi_link": "LUC: 
ABF2: 841095"
  },
  {
    "caption": " In yeast, the OST1- and ABF2-mediated reporter activity was inhibited by ABI1 (‑RCAR). The subsequent recovery of the response was determined by co-expressed ABA receptors RCAR1-RCAR14 belonging to three subfamilies, in the presence or absence of 30 µM ABA. The ABA response is expressed relative to the response obtained by replacing ABI1 with the catalytically inactive ABI1D177A. Regulation of an ABA-responsive LUC reporter in Arabidopsis protoplasts by ectopic expression of 1 µg ABI1-effector in combination with 5 µg ABA receptor DNA (± 10 µM ABA) per sample containing 105 protoplasts. Data information: In (A) each bar represents the mean ± s.e.m; n = 12, biological replicates (derived from four independent yeast transformants); for RCAR1/RCAR5 and RCAR3/RCAR13 18 and 15 biological replicates were used, respectively. Outliers detected by Grubbs-test were removed from the analysis. In (B) each bar represents the mean ± s.e.m of three independent transformations normalized to the activity of a control samples without RCAR and ABA.",
    "ncbi_link": "LUC: 
ABF2: 841095
OST1: 829541"
  },
  {
    "caption": " Expression of the SnRK2s in yeast revealed ABF2-mediated transactivation by SnRK2.1, SnRK2.4, SnRK2.5, and SnRK2.10 in addition to OST1. Inset: Immuno-detection of FLAG-tagged SnRK2s expressed in yeast. The data in (B) are normalized to control samples expressing ABF2 but no SnRK2 ",
    "ncbi_link": "ABF2: 841095
OST1: 829541
SnRK2.1: 830760
SnRK2.10: 842385
SnRK2.4: 837637
SnRK2.5: 836485"
  },
  {
    "caption": " The active subgroup I members together with SnRK2.2 and SnRK2.3 were analyzed for differential activation of ABFs. The OST1 data shown in Fig. 1A is included for better comparison. The induction level of ABF4 relative to the empty vector control (ev) is indicated. ",
    "ncbi_link": "OST1: 829541
SnRK2.2: 824214
SnRK2.3: 836822"
  },
  {
    "caption": " Increased ABF2-mediated reporter expression by OST1 harboring an ABA-box deletion as indicated in D). The data in (E) are normalized to control samples expressing ABF2 but no SnRK2",
    "ncbi_link": "ABF2: 841095
OST1: 853455"
  },
  {
    "caption": " Inhibition of OST1 and SnRK2.4 by clade A PP2Cs. The data in (G) to cells expressing inactive ABI1D177A instead of ABI1. ",
    "ncbi_link": "ABI1: 828714"
  },
  {
    "caption": "A,B) ABF2-mediated reporter induction by different SnRK2s was assessed in the presence of the receptor complex RCAR11 and ABI1, and varying exogenous ABA concentrations. Data information: The ABA concentration that provides half maximum response recovery is indicated by dashed vertical lines. represent Replicates were normalized to controls without SnRK2 in (A, B)",
    "ncbi_link": "ABF2: 841095"
  },
  {
    "caption": " C) Maximum ABA response recovery of samples shown in (A,B) relative to the reporter activity of 0.1 mM ABA-treated yeast cells expressing SnRK2s but no ABI1. Data information: Replicates were normalized to controls without ABI1 and RCAR for each SnRK2 in (C). ",
    "ncbi_link": "ABI1: 828714"
  },
  {
    "caption": " D-F) Analysis of the ABA response mediated by OST1 and SnRK2.4 using the receptors RCAR1 (D), RCAR8 (E), and RCAR14 (F). Data information: The ABA concentration that provides half maximum response recovery is indicated by dashed vertical lines. The data in (D-F) are the mean ± s.e.m; n = 12, biological replicates from four independent yeast transformants for OST1 + RCAR1/RCAR8, and SnRK2.4 + RCAR8. ",
    "ncbi_link": "OST1: 853455
SnRK2.4: 837637"
  },
  {
    "caption": "The Arabidopsis pi4kβ1 pi4kβ2 double mutant displays a growth defect and cytokinetic defects. The growth phenotype of the Arabidopsis pi4kβ1 pi4kβ2 double mutant can be complemented by ectopic expression of PI4Kβ1 or PI4Kβ2, or by mCherry-tagged PI4Kβ1 expressed from a genomic fragment. Plants shown are one month old. Scale bar, 10 cm.",
    "ncbi_link": "mCherry: 
PI4Kβ1: 836528
pi4kβ1: 836528
pi4kβ2: 830794
PI4Kβ2: 830794"
  },
  {
    "caption": "The irregularities in the pattern of root epidermal cell division orientation of the pi4kβ1 pi4kβ2 double mutant is also complemented by ectopic expression of PI4Kβ variants, as shown by propidium iodide (PI) staining of five-day-old roots. Arrowhead, oblique cell wall. Insets, magnifications of areas showing cell wall stubs. Scale bars, 50 µm.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794
PI4Kβ: 830794///836528"
  },
  {
    "caption": "Quantifications of cell wall stubs, oblique cell walls and root meristem size (wild type, n = 15 roots; pi4kβ1, n = 15 roots; pi4kβ2, n = 14 roots; pi4kβ1 pi4kβ2, n = 18 roots; pPI4Kβ1:PI4Kβ1, n = 14 roots, pPI4Kβ2:PI4Kβ2, n = 15 roots). n.d., not detected. Data are mean ± SD. Lowercase letters indicate a significant increase of oblique cell walls (Welch ANOVA with Games-Howell post-hoc test; p < 0.0001) or a significant reduction of root meristem size in the pi4kβ1 pi4kβ2 double mutant (one-way ANOVA with post-hoc Tukey HSD; p < 0.001).",
    "ncbi_link": "pi4kβ1: 836528
PI4Kβ1: 836528
pi4kβ2: 830794
PI4Kβ2: 830794"
  },
  {
    "caption": "Complementation of the pi4kβ1 pi4kβ2 phenotype by functional FLAG-PI4Kβ1 expressed from the intrinsic pPI4Kβ1 or by the pKNOLLE promoters, as indicated, shown for one-month-old plants. Scale bar, 10 cm. Complementation with the pKNOLLE-driven construct indicates functionality of PI4Kβ1 during cell plate formation in G2/M phase.",
    "ncbi_link": "FLAG: 
KNOLLE: 819875
PI4Kβ1: 836528
pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "PI staining of pKNOLLE:FLAG-PI4Kβ1 expressed in the pi4kβ1 pi4kβ2 double mutant background indicates rescue of cytokinetic defects. Arrowhead, cell wall stub in the pi4kβ1 pi4kβ2 double mutant. Scale bars, 50 µm.",
    "ncbi_link": "FLAG: 
KNOLLE: 819875
PI4Kβ1: 836528
pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "In vivo localization of mCherry-PI4Kβ1 expressed from the pPI4Kβ1 promoter in root tips of five-day-old complemented pi4kβ1 pi4kβ2 plants. The mCherry-PI4Kβ1 distribution was imaged using a Zeiss LSM880 in Airyscan Virtual Pinhole (VP) mode with the pinhole set to 2. Arrowheads, nascent cell plates decorated by mCherry-PI4Kβ1. Scale bar, 20 µm. Whole-mount immunostaining of five-day-old seedlings expressing mCherry-PI4kβ1 in the pi4kβ1 pi4kβ2 double mutant background using anti-tubulin (red) and anti-mCherry (green) antibodies, and DAPI (blue). (І), (ІІ), magnifications of regions marked in b, representing early and late cytokinetic stages. Scale bars, 20 µm.",
    "ncbi_link": "mCherry: 
PI4Kβ1: 836528
pi4kβ1: 836528
PI4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The ultrastructure of cytokinetic defects was analyzed by transmission electron microscopy of five-day-old root tip meristems. Images shown are from 3 roots (wild type) and 7 roots (pi4kβ1 pi4kβ2 double mutant). In wild type controls (A), vesicles fused at the cell division plane to give rise to tubular network (TN) of a nascent cell plate. White arrowheads, fused vesicles at the division plane. n = 8 cells. In the pi4kβ1 pi4kβ2 double mutant (B), vesicles were delivered to the cell division plane at a similar stage as wild type but did not fuse. The nuclei of both wild type and double mutant cells were at telophase or interphase, as judged by the presence of decondensed chromatin and a nuclear envelope. At this stage, failed cell plate formation was never seen in wild type (A). Black arrowheads, unfused vesicles. n = 6 cells. Unfused vesicles clustered around a cell wall stub (arrow). White arrowheads, light vesicles; black arrowheads, dark vesicles; black arrow, cell wall stub. n = 8 cells. No cross wall was seen in this cell with two nuclei. n = 6 cells. n, nucleus; ne, nuclear envelope. Scale bars in magnified figures, 2 μm; in insets, 1 μm.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The effects of reduced association of PtdIns(4)P with the cell plate on the recruitment of CLC2-GFP were analyzed in root meristem cells of five-day-old plants. Top, Cell plate-associated fluorescence of the PtdIns(4)P reporter, 2×mCherryFAPP1-PH, was monitored at the end of cytokinesis in five-day-old wild type controls or pi4kβ1 pi4kβ2 double mutants, as indicated. Scale bars, 10 µm. Bottom, The intensity of 2×mCherryFAPP1-PH signals was quantified at the end of cytokinesis at the cell plate (left plot) and at the TGN (right plot). Signal intensities at the cell plate were recorded along the dashed lines indicated in the images and normalized to intensities at the apical plasma membrane (wild type, n = 37 cells, 24 roots; pi4kβ1 pi4kβ2, n = 55 cells, 41 roots). TGN intensities were recorded using the Airyscan VP mode, and the mean TGN intensity was normalized to mean apical and basal plasma membrane intensity (wild type, n=30 cells, 22 roots; pi4kβ1 pi4kβ2, n=37 cells, 31 roots). ***, significant differences (p<0.0001) according to two-tailed Mann-Whitney U-tests.",
    "ncbi_link": "FAPP1: 
GFP: 
mCherry: 
CLC2: 818594
pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Image series from live cell time lapse analysis of CLC2-GFP at the cell plate in roots of pi4kβ1 pi4kβ2 seedlings costained with FM4-64, as indicated. Arrowheads, appearance of CLC2-GFP at the cell plate. Times are given relative to the instance when the cell plate contacted the peripheral plasma membrane, defined as t0. Scale bars, 10 μm. Images are from median focal planes chosen from time lapse series recorded as 3D stacks.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Left, quantification of the time of CLC2-GFP appearance at the cell plate in wild type (B) or the pi4kβ1 pi4kβ2 double mutant (C) (wild type, n = 10 cells, 7 roots; pi4kβ1 pi4kβ2, n = 24 cells, 19 roots). Right, quantification of CLC2-GFP at the TGN in interphase cells. Five-day-old roots expressing CLC2-GFP were subjected to immunostaining and the mean TGN intensity was normalized to plasma membrane intensity (wild type, n = 14 cells, 2 roots; pi4kβ1 pi4kβ2, n = 15 cells, 2 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. Panels a-f display data obtained using cytokinetic cells Five-day-old seedlings were immunostained with anti-KNOLLE (green) and counterstained with DAPI (blue). In the pi4kβ1 pi4kβ2 double mutant, diffusion of KNOLLE occurred at the plasma membrane (arrowheads). Scale bars, 10 μm. Quantitative analysis of lateral diffusion of KNOLLE at the plasma membrane (PM) from (A). Data are mean ± SD from four independent experiments. **, a significant difference (p<0.01) according to a two-tailed Student's t test (untreated wild type, n= 97 cells, 25 roots; untreated pi4kβ1 pi4kβ2, n = 142 cells, 44 roots; BFA treated wild type, n = 126 cells, 28 roots; BFA treated pi4kβ1 pi4kβ2, n = 183 cells, 43 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. Panels a-f display data obtained using cytokinetic cells Enhanced accumulation of KNOLLE at the cell plate at the end of cytokinesis in the pi4kβ1 pi4kβ2 double mutant. Five-day-old seedlings were immunostained with anti-KNOLLE antibodies (green) and counterstained with DAPI (blue). Scale bars, 10 μm. Quantification of KNOLLE intensity at the cell plate from (C), normalized to the signal intensity of intracellular compartments. ***, a significant difference (p<0.0001) according to a two-tailed Mann-Whitney U-test (wild type, n = 26 cells, 20 roots; pi4kβ1 pi4kβ2, n = 41 cells, 37 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. Panels a-f display data obtained using cytokinetic cells Enhanced accumulation of PIN2-GFP at the cell plate at the end of cytokinesis in the the pi4kβ1 pi4kβ2 double mutant. Five-day-old seedlings were stained with 2 μM FM 4-64 for 3 minutes at room temperature. Scale bars, 10 μm. Quantification of PIN2-GFP signal at the cell plate from (E), normalized to the intensity at the apical plasma membrane intensity, as indicated by the dashed lines. ***, a significant difference (p<0.001) according to a two-tailed Mann-Whitney U-test (wild type, n = 28 cells, 16 roots; pi4kβ1 pi4kβ2, n = 45 cells, 26 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. panels g-j display data from the analysis of interphase cells. Internalization of PIN2-GFP was tracked overtime in live roots pretreated with 50 μM CHX for 30 min, then washed and incubated with 50 μM CHX and 25 μM BFA. Scale bars, 10 μm. Quantification of punctate signals from (G) induced by BFA in wild type and pi4kβ1 pi4kβ2 double mutants. Data are mean ± SD. *, a significant difference (p<0.05) according to a two-tailed Student's t test; (wild type, n = 116 cells, 6 roots; pi4kβ1 pi4kβ2, n = 110 cells, 7 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Experiments were performed to address possible effects of the pi4kβ1 pi4kβ2 double mutant on endocytosis of markers relevant for cell plate formation. panels g-j display data from the analysis of interphase cells. Delayed internalization of FM 4-64 from the plasma membrane in the pi4kβ1 pi4kβ2 double mutant. Four-day-old seedlings were pulsed with 2 μM FM 4-64 for 3 minutes on ice and then fluorescence was recorded for 20 min. Scale bars, 10 μm. Quantification of intracellular FM 4-64 signal from (i), normalized to apical and basal plasma membrane intensities. ***, a significant difference (p<0.0001) according to a two-tailed Mann-Whitney U-test (wild type, n = 116 cells, 6 roots; pi4kβ1 pi4kβ2, n = 66 cells, 9 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "pi4kβ1 pi4kβ2 double mutant phenotype were recorded. Immunostaining of meristem cells of five-day-old plants using anti-tubulin (green) counterstained with DAPI (false colour red). Asterisks, multiple nuclei in one cell; arrowheads, multiple phragmoplasts in one cell. Dashed lines indicate the outlines of exemplary multinucleated cells. Scale bars, 10 µm.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "pi4kβ1 pi4kβ2 double mutant phenotype were recorded. Whole-mount immunostaining of root tips of five-day-old seedlings. Green, anti-KNOLLE; red, anti-tubulin; blue, DAPI. (І), (ІІ), magnifications of areas highlighted in dashed boxes. Arrowheads, solid phragmoplasts with thicker cell plates. Scale bars, 20 µm.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "pi4kβ1 pi4kβ2 double mutant phenotype were recorded. Quantification of the incidences of multinucleated cells, multiple phragmoplasts and solid phragmoplasts during late cytokinesis (multinucleated cells: wild type, n = 316 cells, 29 roots; pi4kβ1 pi4kβ2, n = 673 cells, 44 roots; multiple phragmoplasts: wild type, n = 64 cells, 29 roots; pi4kβ1 pi4kβ2, n = 188 cells, 44 roots; solid phragmoplast in late cytokinesis: wild type, n = 41 cells, 29 roots; pi4kβ1 pi4kβ2, n = 89 cells, 44 roots). Data are mean ± SD from three independent experiments. n.d. not detected.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The dynamic transitions of phragmoplast microtubules were recorded by live cell time lapse imaging. Five-day-old seedlings expressing mCherry-TUA5 were imaged at 1 frame per 2 min. Times are given relative to the instance when the cell plate contacted the peripheral plasma membrane, defined as t0. Cells are outlined by dashed lines in the first and last frames of each series. White arrowhead, ectopic stabilization of microtubules in central phragmoplasts of the pi4kβ1 pi4kβ2 double mutant. Scale bars, 10 µm. Plot profiles obtained from dashed lines marked in (A). Black arrowhead, ectopic stabilization of microtubules in central phragmoplasts of the pi4kβ1 pi4kβ2 double mutant.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The dynamic transitions of phragmoplast microtubules were recorded by live cell time lapse imaging. 3D projections from time points selected from (A), when the transition to a ring phragmoplast has occurred in wild type, but solid phragmoplast persisted in the double mutant. Scale bars, 10 µm. Duration of phragmoplast persistence during cytokinesis, determined from initiation to disbanding. ***, a significant difference (p<0.001) according to a two-tailed Mann-Whitney U-test (wild type, n = 12 cells, 9 roots; pi4kβ1 pi4kβ2, n = 21 cells, 16 roots).",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The dynamics of the microtubule bundling protein, MAP65-3, were recorded in live cell time lapse analyses of cytokinetic cells from root tips of wild type controls and pi4kβ1 pi4kβ2 double mutants. Image series of 3D projections of GFP-MAP65-3 costained with FM 4-64 in root tips of four-day-old wild type seedlings. The best angle for visualization was obtained by rotation of the x-axis. Images are representative for 8 cells from 5 roots. Scale bar, 10 µm. Image series of 3D projections of GFP-MAP65-3 costained with FM 4-64 in root tips of four-day-old pi4kβ1 pi4kβ2 seedlings. The best angle for visualization was obtained by rotation of the x-axis. Images are representative for 11 cells from 10 roots. Arrowheads, persisting signal of GFP-MAP65-3 in the center of the cell division plane. Scale bars, 10 µm. Plot profiles were obtained from medial confocal planes at time points displaying the transition from disc to ring phragmoplasts, marked by dashed lines in (A) and (B). Arrowhead, persisting signal of GFP-MAP65-3 in the center of the cell division plane. Times in (A-C) are given relative to the instance when the cell plate contacted the peripheral plasma membrane, defined as t0.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "3D reconstruction of ring and disc-shaped immunofluorescence patterns for GFP-MAP65-3 and microtubules, based on super resolution structured illumination microscopy (SIM), costained with DAPI. Top panels, wild type; bottom panels, pi4kβ1 pi4kβ2 double mutants. Scale bars, 10 µm.",
    "ncbi_link": "pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "The functional relations of PI4Kβ isoforms with MPK4 were tested by assessing phenotypes of crosses of the corresponding mutants. Crosses of pi4kβ1 pi4kβ2 and mpk4-2 mutants resulted in combined genotypes with increased growth defects, as indicated. 14-day-old seedlings are shown. Scale bars, 1 cm. Top, The severe growth defects of the combined genotypes were accompanied by increased tissue distortion, as shown by 3D projections after propidium iodide staining of root tips of 14-day-old seedlings. Scale bars, 100 µm. Bottom, Multinucleation of cells was increased in the combined genotypes, as evident from immunofluorescence of microtubules (red) counterstained with DAPI (blue). Asterisks, multiple nuclei in one cell. Dashed lines indicate the outlines of exemplary multinucleated cells. Scale bars, 10 µm.",
    "ncbi_link": "mpk4-2: 828151
pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Quantification of cytokinetic defects, as shownin the bottom panels of (B). Cytokinetic defects were enhanced in pi4kβ1(-/-) pi4kβ2(+/-) mpk4-2(-/-) (for multinucleated cells, including the percentage of multinucleated cells and the average number of nuclei in multinucleated cells, both according to a Welch ANOVA with Games-Howell post-hoc test; ***, p < 0.001; **,p < 0.01 (wild type, n = 1650 cells, 13 roots; pi4kβ1 pi4kβ2, n = 1441 cells, 19 roots; mpk4-2, n = 1429 cells, 16 roots; pi4kβ1(-/-) pi4kβ2(+/-) mpk4-2(-/-), n = 574 cells, 16 roots); and the incidence of cells displaying KNOLLE fluorescence at the cell plate according to a one-way ANOVA with post-hoc Tukey HSD; p < 0.05, lowercase letters (wild type, n = 1981 cells, 13 roots; pi4kβ1 pi4kβ2, n = 1758 cells, 19 roots; mpk4-2, n = 1721 cells, 16 roots, pi4kβ1(-/-) pi4kβ2(+/-) mpk4-2(-/-), n = 660 cells, 16 roots).",
    "ncbi_link": "mpk4-2: 828151
pi4kβ1: 836528
pi4kβ2: 830794"
  },
  {
    "caption": "Left panels, The distribution of mRFPFAPP1-PH was observed at the cell plate at the end of cytokinesis in root meristem cells of wild type controls (top) and mpk4-2 mutants (bottom). Intensity profiles were recorded as indicated by the dashed lines. Scale bars, 10 µm. Right top, intensity of mRFPFAPP1-PH at the cell plate normalized vs. the intensity at the apical plasma membrane (wild type, n = 43 cells, 34 roots; mpk4-2, n = 32 cells, 28 roots). Right bottom, intensity of mRFPFAPP1-PH at the TGN normalized vs. the intensity at the apical plasma membrane (wild type, n = 40 cells, 29 roots ; mpk4-2, n = 26 cells, 23 roots). *, a significant difference (p<0.05) according to a two-tailed Student's test.",
    "ncbi_link": "mpk4-2: 828151"
  },
  {
    "caption": "Co-IP  assays. PSKR1-HA  was co-expressed with CPK28-GFP  or GFP  in N. benthamiana leaves. PSK  (10 μM) or H2O  was injected 2 hours before leaves  sampling. The protein was precipitated using GFP-Trap. Both immunoprecipitated  and input samples were subjected to western blotting  using an anti-HA  or anti-GFP  antibody.",
    "ncbi_link": "CPK28: 
GFP: 
HA: 
PSKR1: 101246169"
  },
  {
    "caption": "A. Co-IP  assay showing that PSK  promotes CPK28-GS2 interaction. GS2-HA  was co-expressed with CPK28-GFP  or GFP  in  N. benthamiana leaves. PSK  (10 μM) or H2O  was injected 2 hours before leaves  sampling. The protein was precipitated by GFP-Trap. Immunoprecipitated  and input samples were subjected to western blotting using an anti-HA  and anti-GFP  antibody. Data information: Experiments were repeated twice with similar results.",
    "ncbi_link": "CPK28: 
GFP: 
HA: 
GS2: 543998"
  },
  {
    "caption": "B. Co-IP  assay showing that CPK28-GS2 interaction  was enhanced in the presence of PSKR1. GS2-HA  and CPK28-GFP  were co-expressed with or without PSKR1-FLAG  in N. benthamiana leaves. The protein was precipitated by GFP-Trap. Immunoprecipitated  and input samples were subjected to  western blotting  using an anti-HA, anti-GFP  or anti-FLAG  antibody. Data information: Experiments were repeated twice with similar results.",
    "ncbi_link": "CPK28: 
FLAG: 
GFP: 
HA: 
GS2: 543998
PSKR1: 101246169"
  },
  {
    "caption": "A. PSK  induces the phosphorylation  of GS2   by CPK28 in vivo. GS2-GFP  was co-expressed with CPK28-HA  (empty vector as a negative control) in N. benthamiana leaves. PSK  (10 μM) or H2O  was injected 2 hours before leaves  sampling. The phosphorylated GS2   protein was precipitated by GFP-Trap, and then immunoblotted  with anti-pSer/pThr and anti-pSer antibodies.",
    "ncbi_link": "CPK28: 
GFP: 
HA: 
GS2: 543998"
  },
  {
    "caption": "C. Site-directed mutation of S334 and S360 residues in GS2  inhibited its phosphorylation  by CPK28.",
    "ncbi_link": "GS2: 543998"
  },
  {
    "caption": "D. Identification of OE-GS2  transgenic lines expressing phospho-mutated versions of GS2  in the gs2  background by western blotting  using an anti-GLN1/GLN2  antibody. Ponceau S staining was used as the loading control.",
    "ncbi_link": "GS2: 543998
gs2: 543998"
  },
  {
    "caption": "H,I. Immunofluorescence images (H) and quantifications (I) of Cyclin B1 and MAD1 kinetochore levels in control (MAD1-WT) or MAD1β HeLa cells (two independent clones: C13 or C24) treated with nocodazole.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "J,K. Immunofluorescence images (J) and quantification (K) of Cyclin B1 and MAD1 kinetochore localisation in doxycycline-inducible MAD1α and β knockouts treated with or without dox for 10 days and then arrested in nocodazole. Cells were selected that had full MAD1 knockout in the doxycycline treatment (this constituted approximately 30% of cells).",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "L. Relative kinetochore volumes occupied by Cyclin B1 and MAD1 (relative to CenpC) in nocodazole-arrested MAD1α and MAD1β cells (calculated from experiments shown in (H,I).",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "A. Western blot analysis of indicated vsv-MAD1-WT or 3EK HeLa clones treated with or without doxycycline for 10 days.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "B. Immunofluorescence images showing MAD1 and ZW10 kinetochore levels in nocodazole-arrested MAD1-WT-C13 AND 3EK-C14 just after nuclear envelope breakdown (early prometaphase) or later in mitosis when the chromatin is condensed (late prometaphase). Note, that early and late prometaphase was defined based on the level of chromatin condensation.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "C,D. Relative kinetochore volumes occupied by MAD1 (C) and ZW10 (D) (relative to CenpC) in MAD1-WT and -3EK cells in early and late prometaphase.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "E. Quantification of MAD1 kinetochore intensity from indicated MAD1-WT and 3EK clones treated as in (B).",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "C. Quantifications (top) and corresponding immunofluorescence images (underneath) of relative kinetochore MAD1 and MAD1-pT716 levels in nocodazole-arrested of MAD1-WT-C14 and MAD1-3EK-C12 cells treated with different doses of AZ-3146 for 30 min. MG132 was included at the time of AZ-3146 addition to prevent mitotic exit. Each dot represents a cell, horizontal lines indicate the median and error bars show the 95% confidence interval. Note, when these vertical bars do not overlap the difference is considered statistically significant at a level of at least p<0.05 (see methods). 30 cells from 3 experiments. Both kinetochore intensity graphs display data that is relative to the WT-C14 untreated controls, which are normalised to 1. The mean level of the normalised controls is indicated by the dotted lines.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "D. Duration of mitotic arrest in MAD1-WT C14 or MAD1-3EK C12 cells arrested in nocodazole and then treated with indicated concentrations of AZ-3146. Note, the 1.25 µM AZ-3146 data is displayed in Figure 4D, but also included here to allow comparison with other drug doses. Graph shows cumulative mean (±SEM) of 3 experiments, 50 cells per condition per experiment.",
    "ncbi_link": "MAD1: 8379"
  },
  {
    "caption": "(d,e) Negative controls. Both wild-type yeast incubated with GST-PXR58A (d) and vps34Δ yeast incubated with GST-PX (e) were virtually unlabelled. Scale bar, 0.5 μm.",
    "ncbi_link": "vps34: 850941"
  },
  {
    "caption": "(b) NIH3T3 cells expressing Atg4C78A were incubated in Earle's balanced salt solution for 1 h. The isolation membrane was observed as parallel membranes with few IMPs. PtdIns(3)P was labelled only in the PF. Scale bar, 0.1 μm. Other examples are presented in Supplementary Fig. 5.",
    "ncbi_link": "Atg4: 23192///115201"
  },
  {
    "caption": "(a) ymr1Δsjl3Δ cells cultured in S(-NC) for 4 h. PtdIns(3)P was labelled in comparable densities in PF and EF of autophagosomal membranes. Scale bar, 0.2 μm.",
    "ncbi_link": "sjl3: 854276
ymr1: 853574"
  },
  {
    "caption": "(b) The PF/EF ratio of the PtdIns(3)P labelling density in autophagosomal membrane (mean±s.e.m.). The ratio was small (that is, PF) in WT, but close to 1 (that is, PF≅EF) in ymr1Δsjl3Δ. The experiment was repeated three times and the number of colloidal goldparticles per μm2 was measured in more than ten randomly selected images.",
    "ncbi_link": "sjl3: 854276
ymr1: 853574"
  },
  {
    "caption": "(a) Diagrams of the deletion-mutation constructs of Keap1 (left) and the corresponding immunoprecipitation assays (right). Each Flag-tagged mouse Keap1 and mutant was expressed in HEK293T cells. At 22 h after transfection, lysates were prepared and immunoprecipitated with anti-Flag antibody. The resulting immunoprecipitates were subjected to SDS-PAGE and analysed by immunoblotting with anti-Flag, anti-p62, anti-Nrf2 and anti-actin antibodies. Data are representative of three individual experiments.",
    "ncbi_link": "Keap1: 50868"
  },
  {
    "caption": "(b) Diagrams of the deletion-mutation constructs of p62 (left) and the corresponding input (upper right) and pull-down assay (lower right). The MBP-tagged mouse p62 deletion mutants conjugated to amylose (AM) resins were incubated with purified GST-tagged mouse Keap1-DC. The pulled-down complexes with the MBP-p62 mutants were subjected to SDS-PAGE and revealed by staining with Coomassie brilliant blue. The bands corresponding to MBP-p62 and its mutants are indicated by black dots. Red arrowheads indicate the band corresponding to GST-Keap1-DC. For details of construct 14 see Supplementary Information, Fig. S3.",
    "ncbi_link": "Keap1: 50868
p62: 18412"
  },
  {
    "caption": "(d) Immunoprecipitation assays. Flag-tagged p62, KIR-deleted p62 (p62 ΔKIR) and a p62 mutant defective in oligomerization (p62 K7AD69A) were expressed in primary mouse hepatocytes by the adenovirus system (left) or in HEK293T cells by transfection (right). Cell lysates were immunoprecipitated with anti-Flag antibody. The resulting immunoprecipitates were subjected to SDS-PAGE and analysed by immunoblotting with anti-p62 and anti-Keap1 antibodies. The bands corresponding to Flag-p62, endogenous p62, Keap1 and actin are indicated. The data shown are representative of three separate experiments.",
    "ncbi_link": "p62: 8878
p62: 18412"
  },
  {
    "caption": "(b) Immunoprecipitation assays. Flag-tagged Keap1 was co-expressed with increasing concentrations of green fluorescent protein (GFP)-p62 (lanes 3-6) in HEK293T cells. Cell lysates were immunoprecipitated with anti-Flag antibody. The resulting immunoprecipitates were subjected to SDS-PAGE and analysed by immunoblotting with anti-Flag, anti-p62 and anti-Nrf2 antibodies. The bands corresponding to Flag-Keap1, endogenous p62, Nrf2 and actin are indicated. Data are representative of three independent experiments.",
    "ncbi_link": "Keap1: 9817
p62: 8878"
  },
  {
    "caption": "(c) The competitive p62 activity against Keap1 was measured by luciferase assay. The expression plasmids for Nrf2, Keap1 and p62 wild-type (w.t.) or its mutants were transfected into Hepa1 cells along with pNqo1-ARE reporter plasmid and pRL-TK as an internal control. At 36 h after transfection, the luciferase activity was measured in accordance with the instructions provided by the manufacturer. Assays were performed twice in triplicate. Data are means and s.d. for six determinations.",
    "ncbi_link": "pNqo1-ARE: 
pRL-TK: 
Keap1: 50868
Keap1: Q9Z2X8///50868
Nrf2: 18024
p62: 18412"
  },
  {
    "caption": "(d) Immunoblot analysis. Flag-tagged p62 and its mutants defective in interacting with Keap1 were overproduced in wild-type and p62−/− primary mouse hepatocytes by the adenovirus system. At 48 h after infection, total cell lysates and nuclear fractions were prepared and subjected to immunoblot analysis with the antibodies specified. The bands corresponding to Flag-p62, endogenous p62, Keap1, Nrf2, Nqo1, actin and Lamin B are shown. Data are representative of three independent experiments. Uncropped images of blots are shown in Supplementary Information, Fig. S11.",
    "ncbi_link": "p62: Q64337///18412"
  },
  {
    "caption": "(e) Quantification of mRNA levels of the detoxification enzymes Nqo1, Gstm1 and Cyp2a5 in hepatocytes overexpressing Flag-p62 and its mutants. Total RNAs were prepared from non-infected or infected hepatocytes and reverse transcribed into their respective cDNAs, which were used as templates in real-time PCR analysis. Values were normalized to the amount of each mRNA in the non-infected hepatocytes. The experiments were performed three times. Data are means ± s.d. for three experiments.",
    "ncbi_link": "Cyp2a5: 13087
Gstm1: 14862
Nqo1: 18104
p62: 18412"
  },
  {
    "caption": "(a) Insolubilization of Keap1 in Atg7-deficient hepatocytes. Liver homogenates from Atg7F/F:Mx1 mice on various days after injection of poly(I)•poly(C) were separated into detergent-soluble and detergent-insoluble fractions with 0.5% Triton X-100. Each fraction was subjected to SDS-PAGE and analysed by immunoblotting with the indicated antibodies. The data displayed are representative of three separate experiments.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(b) Immunoblot analysis of Atg7-deficient (Atg7F/F:Mx1; Atg7F/F shown here as F/F) and Atg7 p62-deficient (Atg7F/F:Mx1:p62−/−) livers. Liver homogenates from mice of the stated genotypes at 12 days after injection of poly(I)•poly(C) were separated into detergent-soluble and detergent-insoluble fractions. Each fraction was subjected to SDS-PAGE and analysed by immunoblotting with the indicated antibodies. Atg7F/F mice in which Atg7 is efficiently expressed at a level similar to that in the wild-type mice were used as control. Data shown are representative of three separate experiments. Uncropped images of blots are shown in Supplementary Information, Fig. S11.",
    "ncbi_link": "Atg7: 74244
Mx1: 17857
p62: 18412"
  },
  {
    "caption": "(c) Quantitative real-time PCR analyses of Nqo1 and Gstm1 in mouse livers. Total RNAs were prepared from livers of the indicated genotypes at 12 days after injection of poly(I)•poly(C). Values were normalized to the amount of mRNA in Atg7F/F liver. Data are means ± s.d. for three experiments.",
    "ncbi_link": "Atg7: 74244
Gstm1: 14862
Nqo1: 18104"
  },
  {
    "caption": "(d) Immunofluorescence analysis of the cellular localization of p62 and Keap1. Liver sections from mice of the indicated genotypes at 28 days after injection of poly(I)•poly(C) were immunostained with anti-Keap1 (top) and anti-p62 (middle) antibodies. Bottom: merged images of Keap1 (green) and p62 (red). Each inset in the Atg7-deficient liver panels is a magnified image of the boxed region. Scale bars, 20 μm.",
    "ncbi_link": "Atg7: 74244
p62: 18412"
  },
  {
    "caption": "(a) Immunoblotting of Atg7-deficient (Atg7F/F:Mx1; Atg7F/F shown here as F/F) and Atg7 Nrf2-deficient (Atg7F/F:Mx1:Nrf2−/−) livers. Liver homogenates from mice of the assigned genotypes at 28 days after injection of poly(I)•poly(C) were separated into detergent-soluble and detergent-insoluble fractions. Total, soluble and insoluble fractions were subjected to SDS-PAGE and analysed by immunoblotting with the indicated antibodies (top section). Total lysates were subjected to SDS-PAGE and analysed by immunoblotting with antibodies against Nqo1, Gstm1 and actin (bottom left section). Nuclear fractions were prepared from the livers of the indicated genotypes at 28 days after injection of poly(I)•poly(C), subjected to SDS-PAGE and analysed by immunoblotting with antibodies against Nrf2 and Lamin B (as control) (bottom right section). Data were obtained from three independent experiments. Uncropped images of blots are shown in Supplementary Information, Fig. S11.",
    "ncbi_link": "Atg7: 74244
Mx1: 17857
Nrf2: 18024"
  },
  {
    "caption": "(b) Immunofluorescence analysis of the cellular localization of p62 and Keap1. Liver sections from mice of the indicated genotypes at 28 days after injection of poly(I)•poly(C) were immunostained with anti-Keap1 (left) and anti-p62 (middle) antibodies. Right: merged images of Keap1 (green) and p62 (red). Each inset in the Atg7-deficient and Atg7 Nrf2-deficient liver panels is a magnified image of the boxed region. Scale bars, 20 μm.",
    "ncbi_link": "Atg7: 74244
Nrf2: 18024"
  },
  {
    "caption": "(c) Quantitative real-time PCR analyses of Nqo1, Gstm1 and Cyp2a5 in mouselivers. Total RNAs were prepared from livers of the indicated genotypes at 28 days after injection of poly(I)•poly(C). Values were normalized to the amount of mRNA in the Atg7F/F liver. Data are means ± s.d. for three experiments.",
    "ncbi_link": "Atg7: 74244
Cyp2a5: 13087
Gstm1: 14862
Nqo1: 18104"
  },
  {
    "caption": "(a) Immunoblotting of Keap1-deficient (Keap1F/F:Alb) and Keap1 Atg7-deficient (Keap1F/F:Atg7F/F:Alb) livers. Liver homogenates from 8-week-old mice of these genotypes were separated into detergent-soluble and detergent-insoluble fractions. Total, soluble and insoluble fractions were subjected to SDS-PAGE and analysed by immunoblotting with the indicated antibodies (top section). Total lysates were subjected to SDS-PAGE and analysed by immunoblotting with antibodies against Nqo1 and actin (bottom section). Data were obtained from three independent experiments. Uncropped images of blots are shown in Supplementary Information, Fig. S11.",
    "ncbi_link": "Alb: 11657
Atg7: 74244"
  },
  {
    "caption": "(b) Quantitative real-time PCR analyses of Nqo1, Mrp4, p62 and Ho-1 in mouse livers. Total RNAs were prepared from livers of 9-week-old indicated genotypes. Values were normalized to the amount of mRNA in the Atg7F/F liver (control). Data are means ± s.d. for three experiments.",
    "ncbi_link": "Ho-1: 15368
Nqo1: 18104
Mrp4: 107849
p62: 18412"
  },
  {
    "caption": "(c) Kaplan-Meier curves of survival of Atg7F/F:Alb and Keap1F/F:Atg7F/F:Alb mice. The survival analysis of control (n = 33), Keap1F/F:Alb (n = 15), Atg7F/F:Alb (n = 12) and Keap1F/F:Atg7F/F:Alb mice (n = 14) was based on a 16-week follow-up period.",
    "ncbi_link": "Alb: 11657
Atg7: 74244
Keap1: 50868"
  },
  {
    "caption": "(d) Liver weight relative to body weight was measured for the different genotypes. Data are means ± s.d. for Atg7F/F (control) (n = 24), Keap1F/F:Alb (n = 13), Atg7F/F:Alb (n = 9) and Keap1F/F:Atg7F/F:Alb mice (n = 7). Two asterisks, P 0.01 (Student's t-test).",
    "ncbi_link": "Alb: 11657
Atg7: 74244
Keap1: 50868"
  },
  {
    "caption": "(f) Liver function tests of the mice used in d. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Data are means ± s.d. for Atg7F/F (control) (n = 24), Keap1F/F:Alb (n = 13), Atg7F/F:Alb (n = 9) and Keap1F/F:Atg7F/F:Alb mice (n = 7). Two asterisks, P 0.01.",
    "ncbi_link": "Alb: 11657
Atg7: 74244
Keap1: 50868"
  },
  {
    "caption": "(A, B) BMDCs were infected with Pru parasites  (at a MOI of 4 parasites/BMDC) or treated with tunicamycin (TN) for 16h and the expression of UPR target genes were analyzed by RT-qPCR. The results are expressed as (Log2) Fold change (A) or relative mRNA level (B) compared to non-infected  (NI) conditions.  IRE1α/XBP1s pathway: Ern1  (IRE1α), Xbp1s,  Dnajb9 (ERdj4), Sec24D, Bloc1s1  and Sec61a1; PERK/ATF4  pathway: Atf4, Ddit3 (CHOP) and  Ppp1r15a (GADD34); ATF6 pathway: Atf6 and Herpud1; classical ER chaperons: Hspa5 (BIP) and Hsp90b1  (GRP94). Results are normalized to the housekeeping gene Gapdh. Unpaired Student T-test, ns: p>0.05; **: p<0.01; ***: p<0.001; mean ± S.E.M (n=2-5 independent experiments depending of the studied gene, 3 mice  / independent experiment).",
    "ncbi_link": "Atf4: 11911
ATF4: 11911
Atf6: 226641
ATF6: 226641
Bloc1s1: 14533
CHOP: 13198
Ddit3: 13198
Dnajb9: 27362
ERdj4: 27362
PERK: 13666
Ern1: 78943
IRE1α: 78943
Gapdh: 14433
Herpud1: 64209
Hsp90b1: 22027
GRP94: 22027
BIP: 14828
Hspa5: 14828
GADD34: 17872
Ppp1r15a: 17872
Sec24D: 69608
Sec61a1: 53421
Xbp1s: 22433
XBP1s: 22433"
  },
  {
    "caption": "(C, D)  Immunoblot analysis of  IRE1α, PERK, Phospho-PERK (detected by the presence of a second upper band after migration on a 6% acrylamide gel),  Phospho-eIF2α, CHOP and XBP1s protein expression in non-infected BMDCs, BMDCs treated with TN and Pru infected BMDCs (C) and in non-infected and Pru infected Flt3/Notch-DCs (D) for the  indicated times. GAPDH and tubulin were used as loading controls. The same blots are shown in Figure EV3B-C.",
    "ncbi_link": "Flt3: 14255
Notch: 18132///18131///18129///18128"
  },
  {
    "caption": "(D) mRNA relative expression level  of Xbp1s, Dnajb9  (ERdj4), Ddit3 (CHOP) and Ppp1r15a (GADD34) from WT and MyD88KO BMDCs infected with  Pru parasites for 16h compared to non-infected (NI) conditions. Results are normalized to the housekeeping gene Gapdh. Two-way ANOVA Tukey's multiple comparisons, ns: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001, ****: p<0.0001; mean ± S.E.M (n=4-5  mice  pooled from 2 independent experiments).",
    "ncbi_link": "CHOP: 13198
Ddit3: 13198
Dnajb9: 27362
ERdj4: 27362
Gapdh: 14433
MyD88: 17874
GADD34: 17872
Ppp1r15a: 17872
Xbp1: 22433"
  },
  {
    "caption": "(A) BMDCs (CD11c+) were incubated with Pru-Tomato parasites for 16h. Infected cells (red gating) and non-infected bystander cells (green gating) were sorted-purified and further analyzed. (B) The expression of UPR target genes were analyzed by RT-qPCR in infected and non-infected bystander cells compared to non-infected BMDCs (NI). The results are expressed as relative mRNA level compared to non-infected conditions. Results are normalized to the housekeeping gene Gapdh. Unpaired Student T-test, ns: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001; mean ± S.E.M (n=6 mice pooled from 2 independent experiments). ",
    "ncbi_link": "Gapdh: 14433"
  },
  {
    "caption": "(E) mRNA relative expression level of Il-6, Il-12 and Il-23 from XBP1fl/flIRE1fl/fl, XBP1ΔDC IRE1truncDC and XBP1ΔDC BMDCs infected with Pru parasites for 16 h compared to non-infected (NI) conditions. Results are normalized to the housekeeping gene  Gapdh. Two-way ANOVA Tukey's multiple comparisons, ns: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001; ****: p<0.0001; mean ± S.E.M (n=3-5 mice pooled from 2 independent experiments).",
    "ncbi_link": "IRE1: 78943
Gapdh: 14433
Il-12: 16160
Il-23: 83430
Il-6: 16193
XBP1: 22433"
  },
  {
    "caption": "(I) Graph depicts the expression (indicated as the Mean Fluorescence Intensity) of H-2Kb by Pru Tomato SAG1‐OVA infected XBP1fl/fl IRE1fl/fl treated or not with 4μ8C, XBP1ΔDC IRE1truncDC and XBP1ΔDC BMDCs. Bar graphs depict mean ± S.E.M (n=3 mice, one representative experiment from 2 independent experiments). Tukey's ANOVA one-way test, ns: p>0.05.",
    "ncbi_link": "Tomato: 
SAG1: 28932156
IRE1: 78943
XBP1: 22433"
  },
  {
    "caption": "(E, F) RT-qPCR analysis of the indicated UPR genes among total RNA prepared from splenic cDC1 (E) and cDC2 (F) sorted by flow cytometry  6 dpi from wild-type mice, non-infected (NI) or infected with Pru  parasites. Results were normalized to the housekeeping gene Gapdh and are expressed as relative mRNA level compared to the NI condition. Bar graphs depict mean ± S.E.M. Unpaired Student T-test, ns: p>0.05; *: p<0.05; **: p<0.01; mean ± S.E.M (n=3-5 mice pooled from 2 independent experiments).",
    "ncbi_link": "Gapdh: 14433"
  },
  {
    "caption": "(A) Survival  curves of XBP1fl/flIRE1fl/fl and XBP1ΔDC IRE1truncDC mice infected  intraperitoneally with 500 Pru  parasites. Log-rank (Mantel-Cox) test, p=0,0004; n=10 mice per genotype.",
    "ncbi_link": "IRE1: 78943
XBP1: 22433"
  },
  {
    "caption": "(D, E) Quantification of the number of total (left histogram) and activated (right histogram) (IFNγ-positive) CD4+ T cells (D) and CD8+ T cells (E) in the spleen of control mice (XBP1fl/flIRE1fl/fl) and XBP1ΔDC IRE1truncDC infected for 6 days. Two-way ANOVA Tukey's multiple compare, ns: p> 0.05; *: p <0.05; **: p <0.01; ***: p <0.001; ****: p <0.0001; mean ± S.E.M (n=2 independent experiments combined).",
    "ncbi_link": "IRE1: 78943
XBP1: 22433"
  },
  {
    "caption": "Top: Schematic of the co-culture system used to assess vesicle transfer in transfected cells. Donor cell were transfected with the indicated GFP-fusion proteins and then labeled with DiD. Acceptor cells were transfected with a H2B-mCherry plasmid. After 24 h, the cells were detached, replated in 1:1 ratio and cultured for 4 h. Cells were then fixed and stained with HCS CellMask™ Blue. Bottom: Representative confocal images of co-cultured donor and acceptor CAD cells. Yellow arrows point to DiD-labeled vesicles inside acceptor cells.",
    "ncbi_link": "mCherry: 
H2B: 3018"
  },
  {
    "caption": "Time lapses showing a TNT connecting two transfected cells. Top: GFP-vector transfected cells. Middle: GFP-βCaMKII WT transfected cells. Bottom: GFP-βCaMKII T287D transfected cells. Cells were stained with WGA (white). Yellow arrowheads point out a TNT in each condition. Scale bars represent 10 μm.",
    "ncbi_link": "GFP: 
βCaMKII: 24245"
  },
  {
    "caption": "TNT's average duration between GFP-vector, GFP-βCaMKII WT and GFP-βCaMKII T287D transfected cells. Graph represents the average lifetime of 15-20 TNTs per condition ± SEM. Statistical significance was calculated with respect to control (Ctrl); ** p ≤ 0.01, NS = not significant (one-way ANOVA).",
    "ncbi_link": "GFP: 
βCaMKII: 24245"
  },
  {
    "caption": "Confocal images of untransfected and GFP-βCaMKII WT transfected CAD cells (green), treated or not with Wnt7a. Top: Cells were stained with phalloidin (red) and DAPI (blue). Middle: Phalloidin staining (white) of the cells is shown. Bottom: Pseudocolor images of cells stained with phalloidin highlight the differences in F-actin levels among the treatments. Scale bars represent 5 μm. Anti-actin immunoblot and bar graph showing changes in the ratio between G-actin (in supernatant fraction, s) and F-actin (in the pellet fraction, p) of CAD cells untransfected or transfected with GFP-βCaMKII WT plasmid and treated or not with Wnt7a.",
    "ncbi_link": "GFP: 
βCaMKII: 24245"
  },
  {
    "caption": "Confocal images of CAD cells transfected with GFP-βCaMKII WT plasmid (green) and treated or not with Wnt7a. Cells were fixed and then stained with phalloidin (red) and DAPI (blue). The insets (right panels) show a magnified image of the area depicted in the expanded field images (left). 3D reconstruction shows co-localization of GFP/phalloidin signals. Scale bars represent 10 µm.",
    "ncbi_link": "GFP: 
βCaMKII: 24245"
  },
  {
    "caption": "Representative confocal images of 1 DIV co-cultured donor (D, loaded with Alexa-568 α-syn fibrils) and acceptor (A, labeled with CTG) neurons. Neurons were obtained from WT or βCaMKII K.O. mice. Yellow arrows point to α-syn puncta inside acceptor neurons in both conditions.",
    "ncbi_link": "βCaMKII: 12323"
  },
  {
    "caption": "Average piRNA precursor abundance relative to EV in EV and ints-11 RNAi samples, normalized to the total number of short capped RNA reads mapping to annotated WormBase TSSs (Chen et al., 2013). Error bars represent the standard error of the mean (5 replicates).",
    "ncbi_link": "ints-11: 174310"
  },
  {
    "caption": "Distributions of piRNA precursor length in ints-11 RNAi-treated nematodes compared to empty vector-treated nematodes, obtained from deeply sequencing one pair of libraries (inserts sequenced up to 75nt). Distributions of total sequences (E) and total read counts (F) are shown.",
    "ncbi_link": "ints-11: 174310"
  },
  {
    "caption": "Length distributions of nucleoplasmic and chromatin-bound piRNA precursors in N2 empty vector, N2 ints-11 RNAi, tfiis empty vector, and tfiis ints-11 RNAi nematodes. Length shifts in nascent RNA in tfiis mutants are indicated with dashed vertical lines and arrows. The length distributions were calculated from two merged replicates (see Appendix Figure S2 for the length distributions in each replicate).",
    "ncbi_link": "ints-11: 174310
tfiis: 173960"
  },
  {
    "caption": "Distributions of log2 fold change in CAGE signal corresponding to 2 nt upstream motif-dependent piRNAs upon ints-11 RNAi knockdown in an N2 and a tfiis mutant background calculated from two merged replicates. N2 empty vector was used as a baseline for fold change calculation. Boxplots show the interquartile range with a line at the median; the whiskers extend to the greatest point no more than 1.5 times the interquartile range.",
    "ncbi_link": "ints-11: 174310
tfiis: 173960"
  },
  {
    "caption": "Distributions of log2 fold change in CAGE signal corresponding to 2 nt upstream motif-independent piRNAs upon ints-11 RNAi knockdown in an N2 and a tfiis mutant background. N2 empty vector was used as a baseline for fold change calculation. Boxplots show the interquartile range with a line at the median; the whiskers extend to the greatest point no more than 1.5 times the interquartile range",
    "ncbi_link": "ints-11: 174310
tfiis: 173960"
  },
  {
    "caption": "Epi-ID H3K79 methylation scores of the deletion mutants of members of the Rpd3L and Rpd3S complexes, calculated as described in Appendix Supplementary Methods, where 0 means a wild-type H3K79me level (log2 scale). The gray dots indicate accessory subunits. UpTag and DownTag are barcode reporters in a promoter and terminator context, respectively. Data was obtained on all Rpd3L/Rpd3S subunits except Sds3.",
    "ncbi_link": "Rpd3L: 851220
Rpd3S: 855097
Sds3: 854725"
  },
  {
    "caption": "Snapshot of depth-normalized ChIP-seq data tracks from wild-type and rpd3Δ strains showing 6 kb surrounding the DBP1 ORF, which is the top gene in the heatmap in panel (F). All tracks have the same y axis (0-20 RPM). A snapshot of another top-regulated gene is shown in Fig EV1D.",
    "ncbi_link": "DBP1: 855984
rpd3: 855386"
  },
  {
    "caption": "Heatmap of the H3K79me3/H3 change in rpd3Δ versus wild-type cells, aligned on the TSS. Genes were sorted based on the average ratio in the first 500 bp.",
    "ncbi_link": "rpd3: 855386"
  },
  {
    "caption": "ChIP-seq and RNA-seq data for genes ranked on H3K79me3/H3 in rpd3Δ/WT, smoothed using locally weighed regression. The gray band around the line shows the 95% confidence interval. Vertical dashed lines separate 4 groups with distinct changes upon RPD3 deletion. ChIP-seq data of H3K79me1, H3K79me3 and H2Bub were generated in this study (plotted is the average coverage in reads per genomic content, RPGC), Rpd3 binding, H4ac and WT gene expression data were from (McKnight et al, 2015), and the relative expression in rpd3Δ/WT from Kemmeren et al (2014).",
    "ncbi_link": "RPD3: 855386
rpd3: 855386"
  },
  {
    "caption": "H3K79me3/H3 ChIP-qPCR efficiencies (relative to a non-transcribed region, which was unaffected by RPD3 deletion) in wild-type and in rpd3Δ cells harboring empty or RPD3-encoding CEN plasmids. The H188A and H150A-H151A mutations have previously been shown to abrogate catalytic activity (Kadosh & Struhl, 1998). Error bars indicate standard deviation of three biological replicates. p<0.05 (*), p<0.01 (**) and p<0.001 (***) by two-way ANOVA, comparison to wild type.",
    "ncbi_link": "RPD3: 855386
rpd3: 855386"
  },
  {
    "caption": "Gene set enrichment analysis on genes ranked on H3K79me3/H3 in rpd3Δ/WT; all genes have been ranked and the ranks of the genes in the subsets are indicated by vertical lines. Meiotic (C) and Ume6-bound (D) genes are enriched among the genes at which Rpd3 represses H3K79 methylation, and subtelomeric genes (<30 kb of telomere) (E) are enriched among genes at which H3K79 methylation is decreased in rpd3Δ cells.",
    "ncbi_link": "rpd3: 855386
Rpd3: 855386"
  },
  {
    "caption": "Mass spectrometry analysis of H3K79 methylation in thymuses from 3-week-old mice, either wild-type (Cre-) or with deleted Hdac1 or Dot1L alleles, as indicated. Mean and individual data points of biological replicates; H3K79me0 is the predominant state, the y axis is truncated at 70% for readability. The remaining H3K79 methylation after homozygous Dot1L deletion is probably due to the presence of some cells in which Cre is not expressed (yet). p<0.01 (**) and p<0.001 (***) by two-way ANOVA, comparison to wild type.",
    "ncbi_link": "Cre: 2777477
Dot1L: 208266
Hdac1: 433759"
  },
  {
    "caption": "Kaplan-Meier curves of mice harboring thymocytes with indicated genotypes. An event was defined as death or sacrifice of a mouse caused by a thymic lymphoma. Mice that died due to other causes or were still alive and event-free at the end of the experiment were censored. Mice for which the cause of death could not be determined were removed from the data. Wild-type mice were the Cre- littermates of the mice that were used for the other curves.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Immunoblots showing HDAC1 status and H3K79me/H3K9ac levels in nuclear lysates of Hdac1-proficient (p53-null) and Hdac1-deficient thymic lymphoma cell lines. The top four and bottom two panels are from separate lysates of the same cell lines.",
    "ncbi_link": "Hdac1: 433759
p53: 22059"
  },
  {
    "caption": "Immunoblot showing H2BK120 ubiquitination levels in Hdac1-proficient and -deficient cell lines (two independent lines each).",
    "ncbi_link": "Hdac1: 433759"
  },
  {
    "caption": "Growth curves of Hdac1-proficient and -deficient cell lines that were left untreated or were infected with empty virus (pLKO) or shRNAs against Dot1L and selected with puromycin. Growth curves were determined by a series of resazurin assays, which measure metabolic activity, starting four days post-infection. Error bars indicate the range of two replicates from independent cell lines.",
    "ncbi_link": "Dot1L: 208266
Hdac1: 433759"
  },
  {
    "caption": "Inhibitor dose-response curves of the two DOT1L inhibitors EPZ-5676 (Pinometostat) and SGC-0946 in Hdac1-proficient and -deficient cell lines. Cell viability was measured by a resazurin assay after three days of treatment and measurements were normalized to DMSO-treated cells. Two independent cell lines are plotted separately; error bars indicate the range of two biological replicates.",
    "ncbi_link": "Hdac1: 433759"
  },
  {
    "caption": "C  Immunofluorescence microscopy. Wild-type, FIP200- or ULK1-knockout  Huh-1  cells were immunostained  with indicated antibodies. The mean fluorescence intensities of ULK1  on p62  bodies per cell were quantified in each genotype (n = 249 cells). Horizontal bars indicate medians, boxes the interquartile range (25th-75th percentiles) and whiskers 1.5× the interquartile range; outliers are plotted individually. Statistical analysis was performed by Šidák's test after one-way ANOVA. Scale bars, 10 μm (main panels), 1 μm (inset panels).",
    "ncbi_link": "FIP200: 9821
ULK1: 8408"
  },
  {
    "caption": "D Immunofluorescence microscopy. Wild-type and FIP200-knockout  Huh-1  cells were transfected with GFP-ULK1  or GFP-ULK2  and immunostained  with anti-p62  antibody. The mean fluorescence intensities of ULK1  on p62   bodies in each cell were quantified for each genotype (n = 79 cells). Horizontal bars indicate medians, boxes indicate interquartile range (25th-75th percentiles), and whiskers indicate 1.5× interquartile range; outliers are plotted individually. Statistical analysis was performed by Welch's t-test. Scale bars, 10 μm (main panels), 1 μm (inset panels).",
    "ncbi_link": "GFP: 
ULK1: 
ULK2: 
FIP200: 9821"
  },
  {
    "caption": "A Fluorescence microscopy. GFP-p62, GFP-p62S349E, GFP-p62S349A, or GFP-p62T350A were co-transfected with mCherry  or mCherry-KEAP1  into Huh1 p62 KEAP1  double-knockout cells. Twenty-four hours after transfection, the fluorescence images were observed.",
    "ncbi_link": "GFP: 
mCherry: 
p62: 
KEAP1: 9817
p62: 8878"
  },
  {
    "caption": "E FRAP  analyses of mCherry-KEAP1 localized  in p62  bodies comprised of GFP-p62S349E or GFP-p62S349A. The half-time  of recovery (t50) and mobile fraction  (MF) of mCherry-KEAP1  was measured by FRAP  of whole p62  bodies (n = 7). Data are means ± s.d. Statistical analysis was performed by two-sided Welch's t-test.",
    "ncbi_link": "GFP: 
p62: "
  },
  {
    "caption": "F FLIP  analyses of mCherry-KEAP1 localized  in p62  bodies comprised of GFP-p62S349E or GFP-p62S349A. The fluorescence loss of mCherry-KEAP1  in GFP-p62  bodies (n = 14) was measured 30 min after photobleaching  over a large area of cells.",
    "ncbi_link": "GFP: 
p62: "
  },
  {
    "caption": "G FRAP  analyses of mCherry-KEAP1 localized  in p62  bodies comprised of GFP-p62S349E or GFP-p62S349A. t50  and MF  of mCherry-KEAP1  were measured by FRAP  of the central portions of p62  bodies (n = 10). Data are means ± s.d. Statistical analysis was performed by two-sided Welch's t-test.",
    "ncbi_link": "GFP: 
p62: "
  },
  {
    "caption": "D RNA-seq  analysis of livers  of p62+/+ and p62S351E/+ mice  at P19 (n = 3). Volcano plots of differentially expressed genes in p62+/+ versus  p62S351E/+ mice  (red points: FDR < 0.05 and log2FC > 1, blue points: FDR < 0.05 and log2FC < -1). Green points are the targets of transcription factor NRF2.",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "F Immunoblot  analysis of p62+/+ (n = 7) and p62S351E/+ (n = 3) mice  at P19. Liver  homogenates were subjected to immunoblot  analysis with the indicated antibodies. Bar graphs show the results of quantitative densitometric  analysis. Data are means ± s.e. Statistical analysis was performed by Welch's t-test. Note that both faster and slower migrating bands in the KEAP1 blot  represent translational products from the Keap1  gene.",
    "ncbi_link": "Keap1: 50868
p62: 18412"
  },
  {
    "caption": "G, H Hematoxylin  and eosin  (HE) staining  (G) and immunohistochemical  analysis of NQO1  (H) of livers  from  p62+/+ and p62S351E/+ mice  at P19. Scale bars, 100 μm (low magnification panels), and 10 μm (high magnification panels).",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "i Serum  levels of  aspartate aminotransferase (AST), alanine aminotransferase  (ALT), glucose, total cholesterol, blood urea nitrogen  (BUN), and creatinine  from p62+/+ (n = 4 at P12, n = 10 at P15) and p62S351E/+ (n = 4) mice  at P12 and P15 were measured. IU/l, international units/liter. Data are means ± s.e. Statistical analysis was performed by Tukey's test after one-way ANOVA.",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "D Western blot of the GSTpull‐down using antibodies against Matrin3 and Raver1. Lanes 1 and 2 show 5 and 10% of input, respectively, lanes 3 and 4 show GST‐PTB full‐length pull‐down of wild‐type and Y247Q mutant, respectively, and lanes 5 and 6 show GST‐PTB RRM2 pull‐down of wild‐type and Y247Q mutant, respectively, and lane 7 with pull‐down using GST alone.",
    "ncbi_link": "PTB: 5725"
  },
  {
    "caption": "B FLAGimmunoprecipitation of Matrin3 and Raver1, both with wild‐type and with PRI mutated, and FLAG‐MS2 as a negative control. The immunoprecipitated complex was separated in a SDS-PAGE and subjected to Western blot using antibody against PTB which showed interaction to wild‐type Matrin3 (lane 2) and Raver1 (lane 4). The input was also analysed by Western blot with antibodies against PTB as a loading control and against the FLAG tag to ensure equal expression of proteins.",
    "ncbi_link": "Matrin3: 9782
Raver1: 125950"
  },
  {
    "caption": "C The 20‐residue Raver1 491-511 (lane 1) and the Matrin3 346-365 (lane 3) peptide fused to MS2 were transcribed and translated in vitro (Input) and then pulled down with GST‐PTB or with GST‐SXL as a control. Effects of single mutation of the Matrin3 PRI GILPPP to GIAPPP were also tested (lane 4).",
    "ncbi_link": "Matrin3: 9782"
  },
  {
    "caption": "A Western blot probed for Matrin3 (top panel), PTB (middle panel) and actin (lower panel). Lanes 1-4 contain a twofold dilution of the control C2 sample (lane 1-12.5%, lane 2-25%, lane 3-50%, lane 4-100%). Lanes 4-7 contain equal amount of proteins, as can be confirmed by the anti‐actin (lower panel), of control sample (lane 4), double‐PTB and nPTB siRNA‐treated sample (lane 5), Matrin3 siRNA‐treated sample (lane 6) and triple knockdown of Matrin3, PTB and nPTB (lane 7). Lane 7 is from the same gel and exposure, but some lanes present in the original gel were cropped for clarity, and a black line to indicate cropping was placed.",
    "ncbi_link": "Matrin3: 9782
PTB: 5725
nPTB: 58155"
  },
  {
    "caption": "F RT-PCR validation of Matrin3‐regulated alternative spicing events in the ST7, ACSL3, PLEKHA3, TCF12, VWA5A, PTBP2, PTBP3, C3orf17, ZMYND8, VEZT, PIGX and DMD genes. In each case, triplicates for each condition (C-control, M-Matrin3, PTB/nPTB and Matrin3/PTB/nPTB siRNA transfection samples) were analysed and exon inclusion (EI) percentage is shown beneath the corresponding lane, along with the standard deviation (s.d.).",
    "ncbi_link": "ACSL3: 2181
C3orf17: 25871
DMD: 1756
Matrin3: 9782
PIGX: 54965
PLEKHA3: 65977
PTB: 5725
nPTB: 58155
PTBP2: 58155
PTBP3: 9991
ST7: 7982
TCF12: 6938
VEZT: 55591
VWA5A: 4013
ZMYND8: 23613"
  },
  {
    "caption": "A Matrin3 crosslinking in Matrin3‐regulated pre‐mRNAs where position of crosslinked nucleotides was mapped onto the regulated exon and the 500 nucleotides upstream and downstream of its 3′ss and 5′ss, respectively, the upstream flanking exon and 500 nucleotides downstream of its 5′ss and the downstream flanking exon with 500 nucleotides upstream of its 5′ss. The iCLIP tags were mapped onto silenced ASE (blue, n = 421), enhanced ASE (red, n = 187) and to control ASE (grey, n = 16,242), and percentage of occupancy is plotted.",
    "ncbi_link": "Matrin3: 9782"
  },
  {
    "caption": "B Same as in (A) but using iCLIP tags obtained from PTBiCLIP and mapped onto PTB/nPTB‐regulated ASE, silenced ASE (blue, n = 729), enhanced (red, n = 820) and control ASE (grey, n = 14,599).",
    "ncbi_link": "PTB: 5725
nPTB: 58155"
  },
  {
    "caption": "C, D RT-PCR analysis using primers specific to the ST7 exon 11 (C) and ABI2 exon 8 (D) splicing reporters, respectively, of samples where FLAG‐tagged Matrin3 and its mutants have been overexpressed. Quantification of at least three replicates for each condition is shown as a histogram of the percentage of exon inclusion. *P 0.01 compared with control sample (−).",
    "ncbi_link": "ABI2: 10152
Matrin3: 9782
ST7: 7982"
  },
  {
    "caption": "E Western blot of overexpressed FLAG‐tagged Matrin3 and PTB, in control siRNA and PTB/nPTB siRNA‐transfected cells, probed with anti‐FLAG to detect overexpressed proteins, anti‐PTB to detect the knockdown levels and anti‐actin to confirm protein loading. A titration of control sample (lane 1-12.5%, lane 2-25%, lane 3-50% and lane 4-100%) is also included to assess the levels of knockdown. The band present above the PTB doublet in lane 6 is FLAG‐tagged PTB.",
    "ncbi_link": "PTB: 5725
nPTB: 58155"
  },
  {
    "caption": "F, G RT-PCR analysis using primers specific to the ST7 exon 11 (F) and ABI2 exon 8 (G) splicing reporters, respectively, of samples where Matrin3 or PTB expression vectors were co‐transfected, in control siRNA and PTB/nPTB siRNA‐transfected cells. Quantification of at least three replicates for each condition is shown as a histogram of the percentage of exon inclusion. *P 0.01 when compared with control sample in each condition (‐).",
    "ncbi_link": "ABI2: 10152
Matrin3: 9782
PTB: 5725
nPTB: 58155
ST7: 7982"
  },
  {
    "caption": "(D) Left panel: Absorption spectra of dark-adapted XccBphP after illumination with red, far-red, fluorescent white lamp light, sunlight or sunlight filtered through green leaves (LF). Pr/Pfr equilibriums scheme derived from absorption spectra is depicted in the bottom panel. Right panel: The XccBphP-C13S mutant was purified in the presence of BV and its absorption spectra recorded upon illumination with red, far-red and white light or dark adaptation.",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(A-B) A. thaliana plants were inoculated with wild-type, XccbphP, pXccBphP or pC13S bacterial strains cultured prior to inoculation under (A) normal laboratory illumination or (B) under light or dark conditions. After 1, 2 or 3 d.p.i., CFU per plant mg were determined (n = 3 replicates). Data presented here derive from more than 4 independent experiments.",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(E) A. thalianaleaves were inoculated with wild-type, XccbphP, pXccBphP and pC13S strains, stained for callose deposits and observed by fluorescence microscopy. MgCl2 buffer (untreated) and flg22 peptide were used as negative and positive controls, respectively. Top panel: representative pictures of three independent experiments. Scale bar represents 200 µm. Bottom panel: the number of callose deposits per field of view (0.45 mm2) were determined (n = 8 replicates). Data are representative of two independent experiments. (A-E) Values are expressed as mean ± s.e.m. Statistical analysis was performed by a two-tailed Mann-Whitney test (*P < 0.05, **P < 0.01, ***P < 0.001)",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(A) Five µL supernatants from wild-type, XccbphP, pXccBphP and pC13 strains bacterial cultures (OD600 = 1) grown under light or dark conditions were plated onto PYM-carboxymethyl cellulose (CMC) agar plates and revealed with Congo redstaining (n = 2 replicates). The extracellular β-1,4-endoglucanase production levels correlated with CMC degradation halo radiuses (top panel). Halo measurements are presented in the bottom panel. Data derive from 10 independent experiments. (A-B) Values are expressed as mean ± s.e.m. Statistical analysis was performed by a Kruskal-Wallis test and Dunn´s multiple comparison test (*P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(B) The extracellular β-1,4-endoglucanase activity from bacterial cultures supernatants (OD600 = 1) was determined by a colorimetric assay in solution (n = 2 replicates). Wild-type, XccbphP, pXccBphP and pC13 strains were assayed under normal laboratory conditions. Data derive from 3 independent experiments. (A-B) Values are expressed as mean ± s.e.m. Statistical analysis was performed by a Kruskal-Wallis test and Dunn´s multiple comparison test (*P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(A) Five µL from wild-type, XccbphP, pXccBphP and pC13S bacterial cultures (OD600 = 1) were plated onto PYM-glucose agar plates under light or dark conditions. Xanthan production was determined measuring colony diameters (n = 4 replicates) for 20 independent experiments. (A-B) Values are expressed as mean ± s.e.m. Statistical analysis was performed by a Kruskal-Wallis test and Dunn´s multiple comparison test (*P < 0.05).",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "(B) Wild-type, XccbphP, pXccBphP and pC13S were grown in 20 ml PYM liquid medium under light or dark conditions. Extracellular xanthan was purified by KCl addition and ethanol precipitation, then dried and weighted (n = 2 replicates) for 4 independent experiments. (A-B) Values are expressed as mean ± s.e.m. Statistical analysis was performed by a Kruskal-Wallis test and Dunn´s multiple comparison test (*P < 0.05).",
    "ncbi_link": "XccBphP: "
  },
  {
    "caption": "A Analysis of MNase-digested chromatin DNA fragments from wild-type (WT, sizes indicated in black) and nap1Δ (N, sizes indicated in red) cells by agarose gel electrophoresis. Diagram illustrating reduction of array length in nap1Δ cells.",
    "ncbi_link": "nap1: 853922"
  },
  {
    "caption": "B Frequency distribution of nucleosomal DNA size (WT in grey fill with nap1Δ in blue traces) from H3 ChIP-seq.",
    "ncbi_link": "nap1: 853922"
  },
  {
    "caption": "C Calculation of nucleosome fuzziness as the standard deviation of nucleosome (or tag) positions. See also Appendix Fig S1.",
    "ncbi_link": "tag: "
  },
  {
    "caption": "E Disruption of the Nap1-histone interaction by H2A mutation. Bottom panel: Inputs of the coexpressed proteins (soluble extract) and top panel the material bound to the glutathione affinity column were analyzed by SDS-PAGE and Coomassie staining.",
    "ncbi_link": "H2A: 444528"
  },
  {
    "caption": "D-I Mass spectra of yNap1 variants in the absence and presence of H2A-H2B. yNap1 in complex in the absence (D) or presence of H2A-H2B (E). yNap1c in the absence (F) or bound to H2A-H2B (G). The oligomerization mutant yNap1_IF1 alone (H) or in complex with H2A_IF2Δ14-H2BΔ28 (I). yNap1 is shown in green circles and H2A-H2B as red and blue asterisks.",
    "ncbi_link": "Nap1: 853922"
  },
  {
    "caption": "C Analysis of MNase-digested chromatin DNA fragments from wild-type (BY4741), nap1Δ, and nap1Δ cells complemented with different yNap1 expression plasmids. Total MNase units per 50 ml of culture are indicated on the bottom of the lanes. Kb+: DNA Marker.",
    "ncbi_link": "Nap1: 853922
nap1: 853922"
  },
  {
    "caption": "A Mass spectrometric analysis of LSD1 methylation. Immunoprecipitation (IP) was performed using anti-Flag antibody in HEK-293T cells overexpressing Flag-tagged LSD1, followed by liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis. The fragmentation of the LSD1 peptide IADQFLGAMYTLPR identified a dimethylated residue at R838.",
    "ncbi_link": "Flag: 
LSD1: 23028"
  },
  {
    "caption": "B Interactions between LSD1 and CARM1 were detected by co-immunoprecipitation (Co-IP) assay with anti-Flag in HEK-293T cells transfected with Flag-LSD1 or Flag-CARM1, respectively.",
    "ncbi_link": "Flag: 
CARM1: 10498
LSD1: 23028"
  },
  {
    "caption": "Protein expression levels of LSD1 in MDA-MB-231 cells transfected with CARM1 shRNAs or control vector, were assessed by western blotting (B) (Error bars represent the mean ± SD, n = 3 experimental replicates, ns = not significant, Student's t-test).",
    "ncbi_link": "CARM1: 10498"
  },
  {
    "caption": "relative mRNA expression levels of LSD1 in MDA-MB-231 cells transfected with CARM1 shRNAs or control vector, were assessed by qPCR analysis (C) (Error bars represent the mean ± SD, n = 3 experimental replicates, ns = not significant, Student's t-test).",
    "ncbi_link": "CARM1: 10498
LSD1: 23028"
  },
  {
    "caption": "F MDA-MB-231 cells were transfected with control or CARM1 shRNAs and then treated with MG132 or DMSO for 10 h, and the cell lysates were analyzed by western blotting.",
    "ncbi_link": "CARM1: 10498"
  },
  {
    "caption": "G MDA-MB-231 cells were transfected with CARM1 shRNA#2 or control vector, and then treated with CHX (100 μg/ml) for the indicated time; LSD1 protein level was examined by western blotting.",
    "ncbi_link": "CARM1: 10498"
  },
  {
    "caption": "H MDA-MB-231 cells were transfected with control or CARM1 shRNAs and then treated with MG132 for 10 h. Cell lysates were immunoprecipitated by anti-LSD1 antibody and then analysed by immunoblotting.",
    "ncbi_link": "CARM1: 10498"
  },
  {
    "caption": "J HEK-293T that transfected with LSD1 WT or LSD1 R838A were treated with CHX for the indicated time. LSD1 were examined by western blotting analysis.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "L HEK-293T cells expressing LSD1 WT or LSD1 R838A were treated with or without MS049 for 48 h and MG132 for 10 h. Co-IP assay was performed using anti-Flag and then subjected to western blotting.",
    "ncbi_link": "Flag: 
LSD1: 23028"
  },
  {
    "caption": "A Immunoprecipitation assay was performed using anti-Flag antibody in MM-231-shLSD1-WT/R838A cells. The interaction of LSD1 and DUBs were detected by immunoblotting with indicated antibodies.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "D HEK-293T cells were transfected with USP7 WT or USP7 C223S, then treated with MG132 for 10 h. Cell lysates were immunoprecipitated using anti-LSD1 antibody followed by immunoblotting analysis.",
    "ncbi_link": "USP7: 7874"
  },
  {
    "caption": "E MDA-MB-231 cells overexpressing Flag-tagged LSD1 WT/R838A after knockdown of endogenous LSD1 and then treated with or without P5091 for 48 h and MG132 for 10 h. Cell lysates were immunoprecipitated by anti-Flag antibody and then analysed by immunoblotting.",
    "ncbi_link": "Flag: 
LSD1: 23028"
  },
  {
    "caption": "F MDA-MB-231 cells were transfected with control or CARM1 shRNAs before treated with MG132 for 10 h. And cell lysates were immunoprecipitated with anti-LSD1 then subjected to immunoblotting.",
    "ncbi_link": "CARM1: 10498"
  },
  {
    "caption": "H HEK-293T cells were transfected with USP7 WT or USP7 C223S, then treated with or without MS049 for 48 h and MG132 for 10 h. Cell lysates were immunoprecipitated with anti-LSD1 antibody followed by immunoblotting analysis.",
    "ncbi_link": "USP7: 7874"
  },
  {
    "caption": "Migration assays (24 h) of MM-231-shLSD1-WT/R838A/R838K/R838F cells (A) with or without MS049 treatment. Representative micrographs of migrated cells are shown. Data represent the number of cells derived from mean cell counts of five fields (Error bars indicate the mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ***P < 0.001, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "invasion assays (48 h) of MM-231-shLSD1-WT/R838A/R838K/R838F cells (B) with or without MS049 treatment. Representative micrographs of invaded cells are shown. Data represent the number of cells derived from mean cell counts of five fields (Error bars represent mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ***P < 0.001, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "Migration assays (24 h) of MCF7-LSD1-WT/R838A/R838K/R838F cells (C) with or without MS049 treatment. Representative micrographs of migrated cells are shown. Data represent the number of cells derived from mean cell counts of five fields (Error bars indicate the mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ***P < 0.001, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "D invasion assays (48 h) of MCF7-LSD1-WT/R838A/R838K/R838F cells (D) with or without MS049 treatment. Representative micrographs of invaded cells are shown. Data represent the number of cells derived from mean cell counts of five fields (Error bars represent mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ***P < 0.001, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "E MM-231-shLSD1-WT/R838A/R838K/R838F cells (1×106) were injected into the tail veins of 5-week-old female nude mice, and 7 weeks later, mice were sacrificed with euthanasia and lungs were fixed in paraformaldehyde solutions. The number of visible surface metastatic lesions in lungs was counted (mean of 7 mice) (Data are mean ± SD, n = 7 mice for each group, *P < 0.05, **P < 0.01, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "MDA-MB-231 cells were treated with MS049 or P5091. ChIP assays were performed using anti-LSD1 antibody and the immunoprecipitated DNA was analyzed by qPCR using specific primers of E-cadherin (A) promoters (Data are mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, Student's t-test).",
    "ncbi_link": "E-cadherin: 999"
  },
  {
    "caption": "B MDA-MB-231 cells were treated with MS049 or P5091. ChIP assays were performed using anti-LSD1 antibody and the immunoprecipitated DNA was analyzed by qPCR using specific primers of vimentin (B) promoters (Data are mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, Student's t-test).",
    "ncbi_link": "vimentin: 7431"
  },
  {
    "caption": "MM-231-shLSD1-WT/R838A cells were treated with MS049 or P5091, real-time PCR was performed to analysis the E-cadherin (C) mRNA levels (Data are are presented as mean ± SD, n = 3 experimental replicates, **P < 0.01, ns = not significant, Student's t-test).",
    "ncbi_link": "E-cadherin: 999
LSD1: 23028"
  },
  {
    "caption": "D MM-231-shLSD1-WT/R838A cells were treated with MS049 or P5091, real-time PCR was performed to analysis the vimentin (D) mRNA levels (Data are are presented as mean ± SD, n = 3 experimental replicates, **P < 0.01, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028
vimentin: 7431"
  },
  {
    "caption": "MM-231-shLSD1-WT/R838A cells were treated with MS049 or P5091. ChIP assays were performed using anti-LSD1 or anti-H3K4me2 or anti-H3K9me2 antibody, and the immunoprecipitated DNA was analyzed by qPCR using specific primers of E-cadherin (E) promoters (Data are mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ns = not significant, Student's t-test).",
    "ncbi_link": "E-cadherin: 999
LSD1: 23028"
  },
  {
    "caption": "F MM-231-shLSD1-WT/R838A cells were treated with MS049 or P5091. ChIP assays were performed using anti-LSD1 or anti-H3K4me2 or anti-H3K9me2 antibody, and the immunoprecipitated DNA was analyzed by qPCR using specific primers of vimentin (F) promoters (Data are mean ± SD, n = 3 experimental replicates, *P < 0.05, **P < 0.01, ns = not significant, Student's t-test).",
    "ncbi_link": "LSD1: 23028
vimentin: 7431"
  },
  {
    "caption": "A Bar graph and box-and-whisker plots are presented, which show the allelic proportions of WT FOXL2 mRNA and 402C>G FOXL2 mRNA in AGCT tissues from 46 patients analyzed by pyrosequencing. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. X-axis indicates mRNAs of WT FOXL2 and 402C>G FOXL2. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots. Comparisons between groups were performed using Student's t-test, and p values are presented.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "B The relative abundances of WT and variant FOXL2 mRNA were analyzed in KGN and COV434 cells by pyrosequencing (left graph), allele-specific RT-PCR (middle graph) and real-time RT-PCR (right graph). gDNA was detected as a positive control. The relative abundances of the variant FOXL2 mRNA were normalized to that of WT mRNA (set to 1). FOXL2 mRNA levels detected by real-time RT-PCR were normalized to matching gDNA levels. The pyrosequencing data are presented from two independent experiments. The allele-specific semi-quantitative and real-time RT-PCR data are presented as the mean ± SEM from three independent experiments. The p values were analyzed by unpaired, two-tailed Student's t-test (***p < 0.001). n.d. not detected.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "C RNA-decay rates of WT and 402C>G FOXL2 mRNAs in KGN cells were determined after treatment with 5 µg/mL ActD for the indicated times. The estimated half-lives of each transcript are presented. The data are presented as the mean ± SEM from three independent experiments.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "Changes in WT and variant FOXL2 mRNA expression were assessed by RT-PCR (top) and real-time RT-PCR (bottom) (A) after transfecting KGN cells with anti-miRNAs for 48 h.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "C FOXL2 protein levels after transfection of control or miR-1236 were assessed in KGN and COV434 cells.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "D The mRNA levels of WT and variant FOXL2 in control, miR-1236-/+, and miR-1236-/- KGN cells, with or without miR-1236 transfection, were determined by RT-PCR (top) or real-time RT-PCR (bottom).",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "E FOXL2 protein expression in control, miR-1236-/+, and miR-1236-/- KGN cells, and two independent miR-1236-/- (#1 and #2) COV434 cell lines were determined by western blotting.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "B Luciferase activity of the reporter constructs shown in (A) were measured in KGN cells after transfection with an miR-1236 mimic for 48 h. The black arrow indicates the position of 402C>G mutation site.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "D Luciferase activities were measured in KGN cells, using the reporter constructs shown in (C), after transfection with a control miRNA or an miR-1236 mimic for 48 h.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "E, F miR-1236 mutants, in which the C that pairs with G402 of the FOXL2 mutant was substituted with either G (miR-1236-G) (E) or U (miR-1236-U) (F), were cotransfected into KGN cells with one of the reporter constructs described above. Luciferase activities were subsequently determined. Arrows indicate the mismatched sites.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "G In vitro annealing kinetics of miR-1236 with 230 nt-long transcripts of WT or variant FOXL2. 32P-labeled miR-1236 (0.5 nM) was incubated with increasing concentrations of synthetic FOXL2 transcripts (0, 2.5, 12.5, 25, or 50 nM). FOXL2 mRNA-miR-1236 complexes were resolved on a 6% native gel and detected by autoradiography (left). The predicted Kds for the WT and 402C>G FOXL2 transcripts are presented in the right graph.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "Changes in WT and variant FOXL2 mRNA-expression levels were assessed by real-time RT-PCR (A) after transfecting KGN cells with siRNAs against AGO mRNAs for 48 h. The data (mean ± SEM) are from three independent experiments, performed in triplicate.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "C The mRNA levels of WT (left) and variant FOXL2 (right) were determined in KGN cells by real-time RT-PCR, after transfecting a control miRNA or miR-1236. The data (mean ± SEM) are from three independent experiments, performed in triplicate.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "D The mRNA levels of WT and the variant FOXL2 in control (left) and miR-1236-/- KGN cells (right) after transfecting siRNAs against AGO mRNAs were determined by allele-specific real-time RT-PCR. The data (mean ± SEM) are from three independent experiments, performed in triplicate.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "E 293T cells were transfected with an miR-1236 mimic (50 nM) for 24 h, followed by cotransfection with expression vectors encoding FLAG/HA-tagged variants of the indicated human AGOs and pGL3c-CDS-MT for 24 h. The empty p3XFLAG-CMV-10 vector was used as control. Co-immunoprecipitated mRNAs were reverse transcribed, and the cDNA products were used for allele-specific real-time PCR analysis of the FOXL2 variant and GAPDH mRNAs (top). The level of variant FOXL2 mRNA immunoprecipitated using FLAG-tagged AGO proteins was normalized using the level of GAPDH mRNA from the same lysates. The immunoprecipitated-AGO proteins were detected by western blotting (bottom). The data (mean ± SEM) are from three independent experiments.",
    "ncbi_link": "GAPDH: 
FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "F In vivo association of AGO3-mediated miRISC formation with FOXL2 mRNAs are shown. Following transfection of a control miRNA or the miR-1236-G mutant into KGN cells, AGO3-mediated RISC-associated RNAs were isolated by immunoprecipitation with an anti-AGO3 antibody. IgG was used as a control. The co-immunoprecipitated mRNAs were reverse transcribed using a FOXL2-430-R primer binding downstream of the 402C>G site. The cDNA products were used for FOXL2 allele-specific PCR analysis with the FOXL2-279F primer (Appendix Fig. S1), and a representative result (top left) is shown. Quantitative real-time RT-PCR results that examined FOXL2 mRNAs, normalized using the level of GAPDH mRNA (bottom left), are also presented. Western blot analysis of immunoprecipitated AGO3 and inputs are shown in the right panel. The data are presented as the mean ± SEM of two independent experiments.",
    "ncbi_link": "GAPDH: 
FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "G RNA-seq analysis was performed to determine AGO-expression levels (transcripts per million) from the individual tissues from 20 independent AGCT patients. X-axis represents mRNAs of AGO1 to 4. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots.",
    "ncbi_link": "AGO1: 26523"
  },
  {
    "caption": "A Changes in WT and variant FOXL2 mRNA levels in KGN cells were assessed by real-time RT-PCR after transfecting siRNAs against the indicated factors for 48 h. The data are presented as the mean ± SEM from three independent experiments, performed in triplicate.",
    "ncbi_link": "FOXL2: 668"
  },
  {
    "caption": "B FOXL2 protein-expression levels were determined by western blotting after transfecting KGN cells with control, DHX9, or GW182 siRNAs for 48 h. Quantification of FOXL2 protein expression is presented in the bottom panel. The data are presented as the mean ± SEM from three independent experiments. The p values were analyzed by unpaired, two-tailed Student's t-test (**p < 0.01, ***p < 0.001).",
    "ncbi_link": "DHX9: 1660
GW182: 27327"
  },
  {
    "caption": "D Association of endogenous miR-1236 with RISC components in KGN cells was determined via pulldown assays using immobilized 2′-O-methylated oligonucleotides (2′-O-Me oligos) complementary to miR-1236 followed with a pulldown using streptavidin-coupled Dynabeads and western blot analyses (top). Relative quantification of bound proteins compared with proteins from the input is presented as fold enrichment (bottom). Efficient pulldown of endogenous miR-1236 using the 2′-O-Me oligos was confirmed with depleted miR-1236 in the discarded supernatant following the pulldown (Appendix Fig S8). As a control, 2′-O-Me oligos not complementary to miR-1236 were used. The data are the means ± SEM from three independent experiments. The p values were analyzed by unpaired, two-tailed Student's t-test (*p < 0.05, **p < 0.01).",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "E Following transfection of control siRNA or siDHX9 into KGN cells, AGO3-mediated RISC-associated RNAs were immunoprecipitated using an anti-AGO3 antibody. IgG was used as a control. Co-immunoprecipitated mRNAs were reverse transcribed using a FOXL2-430-R primer binding downstream of the 402C>G site. The cDNA products were used for FOXL2 allele-specific PCR analysis with a FOXL2-279F primer (Appendix Fig S1A), and a representative result obtained by RT-PCR (top) is shown. Quantitative real-time RT-PCR results (middle) are also presented as fold enrichment of FOXL2 mRNAs normalized using the level of GAPDH mRNA. Western blots of immunoprecipitated AGO3 and the inputs are shown in the bottom panel. The data are presented as the mean ± SEM from three independent experiments. Different letters denote statistically significant differences (p < 0.05; Student-Newman-Keuls test).",
    "ncbi_link": "GAPDH: 
DHX9: 1660
FOXL2: 668"
  },
  {
    "caption": "F We examined whether DHX9 affected the association between miR-1236 and AGOs. After transfecting KGN cells with control siRNA or siDHX9, the total RNA and AGOs-mediated RISC-associated RNAs were isolated following immunoprecipitations using anti-AGO3 or anti-AGO2 antibodies. The AGOs-immunoprecipitated RNAs were extracted using an acidic phenol:chloroform mixture (5:1, pH 4.3) and precipitated with isopropanol using 10% of 3 M NaOAc (pH 5.2). The enrichment of miR-1236 within miRISCs was detected using the TaqMan® microRNA assay in the immunoprecipitated RNAs and normalized using the level of total miR-1236. The data (means ± SEM) are presented as the fold enrichment calculated from three independent experiments. Different letters denote statistically significant differences (p < 0.05; Student-Newman-Keuls test).",
    "ncbi_link": "DHX9: 1660
miR-1236: 100302242"
  },
  {
    "caption": "G, H Luciferase activities of the reporter constructs presented in Fig 3A and C were measured in KGN cells after transfecting the miR-1236 mimic, indicated siRNAs, and either pGL3c-CDS-FOXL2 MT or pGL3c-UTR-FOXL2 MT for 48 h. The data are expressed as the means ± SEM from three independent experiments and were performed in triplicate. The p values were analyzed by unpaired, two-tailed Student's t-test (***p < 0.001).",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "KGN cells were transfected with 200 nM of scrambled control or FOXL2-specific siRNAs for 24 h. Then, KGN cells were further transfected with 20 nM of control miRNA, miR-1236, control anti-miRNA, or anti-miR-1236. The proportion of annexin-V-positive apoptotic cells (A and B) were analyzed by flow cytometry. The data are presented as the mean ± SEM of three independent experiments. Different letters denote statistically significant differences (p < 0.0001; Student-Newman-Keuls test).",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "KGN cells were transfected with 200 nM of scrambled control or FOXL2-specific siRNAs for 24 h. Then, KGN cells were further transfected with 20 nM of control miRNA, miR-1236, control anti-miRNA, or anti-miR-1236. The population at S phase (C and D) were analyzed by flow cytometry. The data are presented as the mean ± SEM of three independent experiments. Different letters denote statistically significant differences (p < 0.0001; Student-Newman-Keuls test). Efficient silencing of FOXL2 using specific siRNAs was confirmed by western blotting.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "E, F KGN cells were transfected with control siRNA or siFOXL2 for 24 h. Then, KGN cells were further transfected with control miRNA or miR-1236 (E) or with control anti-miRNA or anti-miR-1236 (F) for 48 h, and Transwell-migration assays were performed. The migrated cells were imaged under a bright-field microscope (100 × magnification, scale bar = 100 µm). The results are from three independent experiments and represent fold-changes in the average number of cells/field (mean ± SEM). Different letters denote statistically significant differences (p < 0.01; Student-Newman-Keuls test).",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "G, H COV434 cells were transfected with miR-control or miR-1236 for 48 h, after which cell viabilities (G) and migration abilities (H) were measured. The data are presented as the mean ± SEM of three independent experiments. Immunoblots showing no change in FOXL2 protein are presented in the top panel, and images of migrated cells are presented in the right panel. The migrated cells were imaged under a bright-field microscope (100 × magnification, scale bar = 100 µm).",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "I-K The properties of miR-1236-/+ and miR-1236-/- KGN cells versus control KGN cells were assessed by measuring cell viability (I), cell proliferation (J), and cell migration (K). The data are presented as the mean ± SEM of three independent experiments. The migrated cells were imaged under a bright-field microscope (100 × magnification; top of Fig. 6K). Scale bar = 100 µm.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "L No difference in the cell-migration activities of control and two independent miR-1236-/- (#1 and #2) COV434 cell lines. The migrated cells were imaged under a bright-field microscope (100× magnification, scale bar = 100 µm; top) and the results (bottom) represent fold-changes in the average number of cells/field. The data are presented as the mean ± SEM of three independent experiments.",
    "ncbi_link": "miR-1236: 100302242"
  },
  {
    "caption": "The effect of miR-1236 KO on AGCT metastasis was assessed, using an in vivo xenograft mice model. (A) Representative images of tumor nodules (white arrows) formed in the intestines of nude mice xenografted with control or miR-1236-/- KGN cells are shown (left and right; scale bar = 5 mm). Hematoxylin and eosin staining confirmed the pathological characteristics of the metastasized GCT nodules (middle, black arrows; scale bar = 50 µm). The black dashed circles are metastasized nodules of xenografted KGN cells found in mouse intestines. (B) The number of tumor nodules formed in the intestines was counted in control (n = 8) and miR-1236-/- (n = 8) mice.",
    "ncbi_link": "miR-1236: 
miR-1236: 100302242"
  },
  {
    "caption": "(C) Allele-specific real-time RT-PCR analysis of the WT and 402C>G variant FOXL2 mRNAs was performed using RNA extracted from tumor nodules from control or miR-1236-/- mice. The p values were analysed by unpaired, two-tailed Student's t-test (**p < 0.01, ***p < 0.001).",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "D-F Box-and-whisker plots showing the relative expression of miR-1236 (D), variant FOXL2 mRNA (E), and WT FOXL2 mRNA (F), respectively, in 32 patients with non-metastasized AGCTs and 14 patients with metastasized AGCTs. X- axis indicates patient subgroups depending on whether they exhibit metastasized AGCTs (meta) or not (non-meta). The relative miR-1236 levels were measured using a TaqMan® microRNA RT-qPCR assay, with expression normalized to RNU6B. The levels of 402C>G or WT FOXL2 mRNA were determined by real-time RT-PCR, and the data were normalized to paired-gDNA levels. The relative levels of miR-1236 and FOXL2 mRNAs were quantified by setting the levels of AGCT #1 to 1. Real-time RT-PCR was performed in triplicate for each specimen. The box plot represents the minimum value, first quartile, median, third quartile and maximum value of a data set. The whiskers extend to the most extreme data points not considered outliers, and the outliers are represented as dots. Comparisons between groups were performed using Student's t-tests, and p values are presented.",
    "ncbi_link": "RNU6B: 
FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "G, H The estimated regression line superimposed on the scatter plot of miR-1236 levels with 402C>G FOXL2 mRNA (G) or WT FOXL2 mRNA (H) in AGCT samples (n = 46) is shown, along with correlation coefficient (r) and p values.",
    "ncbi_link": "FOXL2: 668
miR-1236: 100302242"
  },
  {
    "caption": "A. Immunoblotting and densitometry quantification of Rab22a in JAWS-IIDCs infected with lentiviruses encoding a random sequence (Scramble) and a shRNA specific for silencing Rab22a (Rab22a KD). Data are representative of at least three independent experiments.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "B. RNA extraction and qPCR quantification of Rab22a in the same cells analyzed in A. Data show mean ± SEM of triplicate values and are representative of two independent experiments. ** P = 0.0047.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "C. IF labeling and confocal microscopy analysis showing the distribution of MHC-I molecules (H-2Kb, green) and Rab22a (red) in Scramble and Rab22a KD JAWS-II DCs. Nuclei stained with DAPI and DIC images are shown on the left. Overlay is shown in the right panels. Scale bars: 5 µm. Data are representative of at least 30 images analyzed for each experimental condition from three independent experiments.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "D. FACS analysis of MHC-I labeled in intact (cell surface) and permeabilized (total) Scramble and Rab22a KD JAWS-II cells. Data represent mean ± SEM of triplicate values and are representative of three independent experiments. P = 0.1082 (ns) and ***P = 0.0003.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "E. MHC-I staining on isolated phagosomes was measured by FACS at the indicated time periods after 3 µm LB internalization by Scramble and Rab22a KD JAWS-II DCs. Data represent mean ± SEM of three independent experiments. ***P < 0.001 at 3 h and *P < 0.05 at 5 h between both DC types.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "F. MHC-I molecules recycling ability was measured by FACS at the indicated time periods by Scramble and Rab22a KD JAWS-II DCs. Data represent mean ± SEM of three independent experiments. *P < 0.05 at 10 min and **P < 0.01 at 20 and 40 min.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "G. The transferrin (Tfn) recycling ability was measured by FACS at the indicated time periods by Scramble and Rab22a KD JAWS-II DCs. Data represent mean ± SEM of three independent experiments. P > 0.05 (ns) at 10, 20 and 40 min.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "A-C. The cross-presentation ability after incubation with A) soluble OVA, B) OVA/BSA-coated beads and C) the SIINFEKL control peptide at the indicated concentrations by Scramble and Rab22a KD JAWS-II DCs was evaluated with the B3Z hybridoma. Data represent mean ± SEM of triplicate values and are representative of three independent experiments. A) ***P = 0.0001 and B) P = 0.1432 (ns); **P = 0.0044. The two-tailed Student's unpaired t test was performed.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "D-E. Evaluation of endocytosis and phagocytosis in Scramble and Rab22a KD JAWS-II DCs. D) The endocytosis of fluorescent OVA after 1 h of internalization and E) the phagocytosis of 3 µm fluorescent LB at different times of internalization were assessed by FACS analysis. The antigen internalization was conducted at 37°C for effective uptake and at 4°C as negative control. Data represent mean ± SEM of triplicate values and are representative of three independent experiments.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "F. The kinetics of OVA degradation, as percentage of proteases inhibitors, in isolated phagosomes at the indicated time periods post-internalization from Scramble and Rab22a KD JAWS-II DCs was assessed by FACS analysis. Data represent mean ± SEM of three independent experiments.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "G. Immunoblotting of Rab22a and Actin in BMDCs infected with lentiviruses encoding a random sequence (Scramble) and two shRNA specific for silencing Rab22a (Rab22a KD #1 and #2).",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "H-I. The cross-presentation capacity after the incubation with H) soluble OVA at the indicated concentrations by Scramble, Rab22a KD #1 and Rab22a KD #2 BMDCs was evaluated as described before for JAWS-II DCs. Data represent mean ± SEM of triplicate values and are representative of two independent experiments. ***P = 0.0001. The two-tailed Student's unpaired t test was performed.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "H-I. The cross-presentation capacity after the incubation with I) the SIINFEKL control peptide at the indicated concentrations by Scramble, Rab22a KD #1 and Rab22a KD #2 BMDCs was evaluated as described before for JAWS-II DCs. Data represent mean ± SEM of triplicate values and are representative of two independent experiments. ***P = 0.0001. The two-tailed Student's unpaired t test was performed.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "J. Soluble OVA was electroporated into the cytosol of Scramble and Rab22a KD JAWS-II DCs and T cell activation was determined 2 h later with the B3Z hibridoma. To control endogenous MHC-I antigen presentation specificity, DCs were also treated with brefreldin A (BFA). The use of this drug markedly reduced CD8+ T cell response to similar levels obtained by DCs without any antigen (∅). Data represent mean ± SEM of triplicate values and are representative of three independent experiments.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "K. Immunoblotting showing the amount of OVA incorporated by Scramble (a) and Rab22a KD (b) JAWS-II DCs after electroporation and BFA treatment.",
    "ncbi_link": "Rab22a: 19334"
  },
  {
    "caption": "A. Scramble and Rab22a KD JAWS-II DCs were infected with OVA-YFP-expressing T. gondii (TgRHYFPSAG1-OVA) for 8 h and confocal images detecting the parasite (green), endogenous Rab22a (red) and GRA6 (magenta) were taken. Top panels: Scramble cells; bottom panels: Rab22a KD cells. White boxes are shown at higher magnification in the insets. The nuclear marker DAPI (blue) and DIC images are shown in the left panels. Overlays are shown in the right panels. Scale bars: 5 µm. Images are representative of at least 30 analyzed from three independent experiments.",
    "ncbi_link": "SAG1: 
Rab22a: 19334"
  },
  {
    "caption": "B. The cross-presentation of OVA secreted by T. gondii (TgRHYFPSAG1-OVA) after 8 h of infection at the indicated MOI was evaluated by B3Z T cell activation. Data represent mean ± SEM of triplicate values and are representative of three independent experiments. ***P < 0.001. A two-way ANOVA and the Bonferroni post-test were performed.",
    "ncbi_link": "SAG1: "
  },
  {
    "caption": "C. The efficiency of infection (8 h) of TgRHYFPSAG1-OVA in Scramble and Rab22a KD JAWS-II DCs was measured by FACS analysis at the indicated MOI. Data represent mean ± SEM of duplicate values and are representative of three independent experiments.",
    "ncbi_link": "SAG1: 
Rab22a: 19334"
  },
  {
    "caption": "D. Immunoblotting showing the total amount of OVA in Scramble and Rab22a KD JAWS-II DCs after 90 min and 7 h of infection with TgRHYFPSAG1-OVA parasite at MOI 2 and 6. Fifty µg of total cell lysates were loaded onto each lane. Data are representative of two independent experiments.",
    "ncbi_link": "SAG1: "
  },
  {
    "caption": "HEK293, RPE, or U2OS/MycBioID-FAM111A cell lines were induced with doxycycline to express wild-type or mutant FAM111A for 24 h (HEK293), 48 h (RPE), or 72h (U2OS). The colonies were fixed then stained with crystal violet.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "Cell-cycle profiles of HEK293, RPE and U2OS FAM111A-expressing cell lines that were induced with doxycycline for 48 h and analyzed by flow cytometry.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "C. HEK293 cell lines were induced with doxycycline to express wild-type or mutant FAM111A for 24 h (HEK293) Cell growth was quantitated as total area on ImageJ. Values are mean ± s.e.m. of independent experiments (n = 3). *p<0.05, **p<0.01, ****p<0.0001 (two-tailed unpaired t-test).",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "D. Cell-cycle profiles of HEK293 FAM111A-expressing cell lines that were induced with doxycycline for 48 h and analyzed by flow cytometry.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "A. HEK293 or U2OS/MycBioID-FAM111A cell lines were induced with doxycycline for 24 h. Total protein from 105 cells was resolved by SDS-PAGE, and probed in western blots for both endogenous FAM111A (71 kDa) and MycBioID-FAM111A (110 kDa) as well as full length and cleaved PARP (116 and 89 kDa, respectively). The Tubulin western blot is a sample loading control.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "B. HEK293/MycBioID-FAM111A cell lines with no treatment (- Dox), or treated with doxycycline, along with DMSO or 100 μM Z-VAD-FMK for 24 h (total inhibition of PARP cleavage was also observed when 50 μM Z-VAD-FMK was used). Total protein from ~ 105 cells was resolved by SDS-PAGE, and probed in western blots with Myc, PARP, or Tubulin antibodies.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "D. DMSO or Z-VAD-FMK treated HEK293/MycBioID-FAM111A cell lines were induced with doxycycline for 24 h. Total protein from an equal number of cells was incubated with magnetic streptavidin beads, and pull downs were analyzed by western blotting using GANP and Myc antibodies.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "E. HEK293/MycBioID-FAM111A cell lines were induced with doxycycline for 24 h, while growing in the presence or absence of 50 mM supplemental biotin. Total protein from whole cell lysates was incubated with magnetic streptavidin beads. Pulldowns were analyzed by western blotting using GANP and Myc antibodies.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "F. DMSO or Z-VAD-FMK treated HEK293/MycBioID-FAM111A cell lines were induced with doxycycline for 24 h. Total protein from ~ 105 cells was resolved by SDS-PAGE, and probed in western blots using antibodies against NPC (Mab414), PARP, cleaved Caspase 3, Myc, or Tubulin.",
    "ncbi_link": "FAM111A: 63901"
  },
  {
    "caption": "A. Representative immunofluorescence images of SV40 LT localization 72 h after transfection into U2OS cells infected with control or FAM111A shRNA. Images were taken with a Zeiss Axio Imager. LT is shown in green, and DAPI blue. Scale bar: 100 μm. B. Quantification of LT positive cells described in A and fixed at indicated times post transfection. Five hundred or more cells were counted for each condition. C. Quantification of RFP marker distribution upon co-transfection with SV40 LT variants into U2OS cells infected with control or FAM111A shRNA. Cells were fixed at the indicated times. Five hundred or more cells were counted for each condition. In B & C, values are mean ± s.d. of independent experiments (n = 3). *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 (two-tailed unpaired t-test). ",
    "ncbi_link": "FAM111A: 63901
LT: 29031019"
  },
  {
    "caption": "D. Western blot analysis of control or FAM111A-depleted U2OS cells transfected with SV40 LT variants. Cells were collected and lysed at indicated timepoints after SV40 transfection, immunoblotted with FAM111A, LT, or PARP antibodies. Cdc2-PSTAIR was used as a loading control.",
    "ncbi_link": "FAM111A: 63901
LT: 29031019"
  },
  {
    "caption": "(H) Knockdown of two autophagy genes, atg-7 and lgg-1 significantly reduce the number of generated exophers. n = 91-103; N = 3.",
    "ncbi_link": "atg-7: 178005
lgg-1: 174050"
  },
  {
    "caption": "(B) Feminized hermaphrodites of thermosensitive a fem-1 mutant strain do not produce exophers regardless of growth temperature. This phenotype can be partially rescued by mating fem-1 mutants with males. n = 10-26; N = 2.",
    "ncbi_link": "fem-1: 177335"
  },
  {
    "caption": "(F) Increased eggshell permeability caused by emb-27 knockdown elevates exopher production. n = 103 and 89; N = 3.",
    "ncbi_link": "emb-27: 174314"
  },
  {
    "caption": "(E) RNAi knockdown of the egg yolk precursor protein VIT-1 increases the number of muscular exophers. n = 20; N = 2.",
    "ncbi_link": "VIT-1: 181034"
  },
  {
    "caption": "(G) RNAi knockdown of RME-2 yolk receptor abolish exopher production. n = 110-123; N = 3.",
    "ncbi_link": "RME-2: 177329"
  },
  {
    "caption": "A. Bclaf1  wild type (WT) and two Bclaf1 knockout HeLa cell lines (KO-1 and -2) were pre-treated with  DMSO or cycloheximide  (CHX, 1 μg/ml) for 30 min, and then treated with TNF (10 ng/ml) together with CHX for 12 hours. Afterwards, the cells were subjected to Annexin V/7AAD staining  followed by flow cytometry analysis, all Annexin V positive cells were counted for analysis, or protein extractions followed by western blotting analysis. B, C. HeLa (B) or primary MEFs (C) were transfected with control (siCtrl) or two siRNAs against Bclaf1 (siBclaf1-1 and -2) and then treated and analyzed as described in A. Data information: Data are shown as mean ± SD. n=3 biological replicates. ns, not significant; **p<0.01; ****p<0.0001. One-way ANOVA test.",
    "ncbi_link": "Bclaf1: 9774
Bclaf1: 72567"
  },
  {
    "caption": "D, E. MEFs transfected with control (siCtrl) or siBclaf1-1 and/or siBclaf1-2 siRNAs were pre-treated with  CHX (1 μg/ml)/z-VAD (20 μM) (D) or SM-164 (100 nM)/z-VAD (20 μM) (E) for 30 min, and then added TNF (10 ng/ml) for indicated times. The cells were subjected to  Annexin V/7AAD staining after 9 hours followed by flow cytometry analysis for 7AAD positive and  Annexin V  negative cells (up), or protein extractions and western blotting analysis at indicated time periods (down). Data information: Data are shown as mean ± SD. n=3 biological replicates. ns, not significant; **p<0.01; ****p<0.0001. One-way ANOVA test. ",
    "ncbi_link": "Bclaf1: 72567"
  },
  {
    "caption": "A, B. Cell lysates of HeLa Bclaf1 WT and KO cells (A), and HeLa cells transfected with siCtrl or siBclaf1-1 (B) treated with  TNF (10 ng/ml) for indicated time periods were analyzed by western blotting with the indicated antibodies.",
    "ncbi_link": "Bclaf1: 9774"
  },
  {
    "caption": "C, D. HeLa Bclaf1 WT and KO cells (C), and  HeLa cells transfected with siCtrl or siBclaf1-1 (D) were treated with  TNF (10 ng/ml) for the indicated time periods, and then subject to nucleus-cytoplasm fractionation as described in materials and methods followed by western blotting. Tubulin and histone H3  were used as loading controls for cytoplasmic and nuclear fractions, respectively.",
    "ncbi_link": "Bclaf1: 9774"
  },
  {
    "caption": "G, H. HeLa  cells transfected with siRNAs against Bclaf1 or c-FLIP were pretreated with CHX (1 μg/ml) for 30 min and then stimulated with  TNF (10 ng/ml) in the presence of  CHX for 12 hours followed by Annexin V/7AAD staining and flow cytometry analysis (G), or protein extractions followed by western blotting analysis (H). Data information: Data are shown as mean ± SD. n=3 biological replicates. **p<0.01; ****p<0.0001. One-way ANOVA test.",
    "ncbi_link": "Bclaf1: 9774
c-FLIP: 8837"
  },
  {
    "caption": "A-F. Bclaf1 WT, KO-1 and -2 HeLa  cells (A and D), as well as HeLa (B and E) and primary MEFs (C and F) which were transfected with siCtrl or siBclaf1-1 and -2 were treated with TNF (10 ng/ml) for 6 hours followed by western blotting analysis (A-C), or for 4 hours followed by total RNA extraction and RT-PCR  analysis (D-F). Data information: Data are shown as mean ± SD. n=3 biological replicates. *p<0.05; ***p<0.001; ****p<0.0001. One-way ANOVA test.",
    "ncbi_link": "Bclaf1: 9774
Bclaf1: 72567"
  },
  {
    "caption": "H, I.  CHIP  analysis of the  binding of Bclaf1 to the promoter of CFLAR was performed in HeLa-Flag-Bclaf1 cells treated without (H) or with TNF (I). The regions amplified by  RT-PCR were delineated. Data information: Data are shown as mean ± SD. n=3 biological replicates. *p<0.05; ***p<0.001; ****p<0.0001. One-way ANOVA test. ",
    "ncbi_link": "Flag: 
Bclaf1: 9774
CFLAR: 8837"
  },
  {
    "caption": "B. CFLAR promoter were co-transfected with Bclaf1 or/and p50 into HeLa-Bclaf1-KO cells, and the  luciferase activity was measured as described before.",
    "ncbi_link": "p50: 51008
Bclaf1: 9774
CFLAR: 8837"
  },
  {
    "caption": "E, HeLa  cells were transfected with siCtrl or siRNA against Bclaf1 or p50 were pre-treated with DMSO or CHX  (1 μg/ml) for 30 min, and then treated with TNF (10 ng/ml) for 12 hours. Cells were lysed and then analyzed by  western blotting",
    "ncbi_link": "p50: 51008
Bclaf1: 9774"
  },
  {
    "caption": "G. CHIP  analysis of the CFLAR promoter in HeLa-Flag-Bclaf1 cells. Immunoprecipitation was performed using anti-Flag and control IgG antibodies followed by RT-PCR analysis. Data information: Data are shown as mean ± SD. n=3 biological replicates. ns, not significant; *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. One-way or Two-way ANOVA test.",
    "ncbi_link": "CFLAR: 8837"
  },
  {
    "caption": "A. HeLa-Flag-Bclaf1 and Bclaf1  WT HeLa cells treated with or without TNF  (10 ng/ml) for 2 hours were separated into the cytoplasmic and the nuclear fraction. Endogenous Flag-Bclaf1 complex in each fraction was immunoprecipitated with M2 beads and analyzed by western blotting.",
    "ncbi_link": "Flag: 
Bclaf1: 9774"
  },
  {
    "caption": "B. HeLa-Flag-Bclaf1 cells transfected with siCtrl or sip65 were treated with TNF (10 ng/ml) for 2 hours. The nuclear fraction was isolated and subjected to  immunoprecipitation with an anti-Flag  or control IgG antibody, followed by western blotting analysis.",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "D. CFLAR FL promoter were co-transfected with p50 and Bclaf1 FL or its individual deletion mutant into HeLa-Bclaf1-KO cells. The experiments were performed in triplicate with a  Renilla reporter in the transfection mixture for normalization. Data information: Data are shown as mean ± SD. n=3 biological replicates. ns, not significant. One-way ANOVA test. ",
    "ncbi_link": "p50: 51008
Bclaf1: 9774
CFLAR: 8837"
  },
  {
    "caption": "siRNAs against Bclaf1  and control siRNAs (siCtrl) mixed with in vivo-jetPEI (Polyplus) were injected into C57BL/6 mice. The mice were then treated with mTNF for two hours before sacrifice. The small intestines were excised and processed for immunohistochemical staining for Bclaf1 (B) and Hematoxylin-and-eosin staining (C) Bclaf1 knockdown efficiency is detected by  immunohistochemical analysis (B). Hematoxylin-and-eosin staining showing the morphological change (C). Villus height and crypt depth were measured (D). Data are shown as mean ± SD. n=5 mice for each group. ns, not significant; **p<0.01; ***p<0.001; ****p<0.0001. One-way ANOVA test. Scale bars: 50 μm in B, 100 μm in C.",
    "ncbi_link": "Bclaf1: 72567"
  },
  {
    "caption": "siRNAs against Bclaf1 and control siRNAs (siCtrl) mixed with in vivo-jetPEI (Polyplus) were injected into C57BL/6 mice. The mice were then treated with mTNF for two hours before sacrifice. The small intestines were excised and processed for immunohistochemical staining  for cleaved caspase 3 (E), phospholated RIPK3  (F) CC3+ and p-RIPK3+ positive cells in five fields per  intestine  were quantified. Data are shown as mean ± SD. n=5 mice  for each group. ns, not significant; **p<0.01; ***p<0.001; ****p<0.0001. One-way ANOVA test. Scale bars: 50 μm",
    "ncbi_link": "Bclaf1: 72567"
  },
  {
    "caption": "siRNAs against  Bclaf1 and control siRNAs (siCtrl) mixed with in vivo-jetPEI (Polyplus) were injected into C57BL/6 mice. The mice were then treated with mTNF for two hours before sacrifice. The  small intestines were excised and processed for  western blotting analysis (G).",
    "ncbi_link": "Bclaf1: 72567"
  },
  {
    "caption": "HIEC-6 cells were transfected siCtrl or siBclaf1-1 and -2. Then the cells were treated with TNF for 24 hours were subjected for protein extractions and western blotting analysis (I and J)",
    "ncbi_link": "Bclaf1: 9774"
  },
  {
    "caption": "A. Blood-stage growth rate of concavin(-) parasites in comparison to wild type. Data points represent parasites growing in individual mice, n indicates total number. P-value is calculated using the Mann Whitney test. Shown is the mean ± SEM.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "B. Gametocyte to ookinete conversion of 3 biological replicates. P-value calculated using the Mann Whitney test. Shown is the mean ± SEM. C. Average speed of moving ookinetes. Data points represent individual ookinetes, n indicates total number of cells from 3 biological replicates. P-values are calculated using the Kruskal Wallis test followed by Dunns multiple comparison. D. Ookinete images of wild type and concavin(-) parasites revealing similar cell shapes. Scale bar 5 µm.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "E. Oocyst development of concavin(-) parasites compared to wild type. Data points represent individual midguts observed between d12-17 post infection from 3 independent cage feeds. Shown is the mean ± SEM. P-values are calculated using the Kruskal Wallis test followed by Dunns multiple comparison.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "A. Oocyst development of concavin(-) parasites complemented with either the P. berghei  gene or the P. falciparum  orthologue fused to GFP. Data points represent individual midguts observed between d12-17 post infection of 3 independent cage feeds. Shown is the mean ± SEM. P-values are calculated using the Kruskal Wallis test followed by the Dunns multiple comparison test.",
    "ncbi_link": "GFP: 
concavin: 55152263"
  },
  {
    "caption": "C. Sum table of mosquito infections of wild type, concavin(-) and complemented lines expressing either P. berghei (Pb) or P. falciparum  (Pf) concavin-GFP. Numbers determined on d17 post mosquito infection. Infection rate contains 3 different countings of at least 20 mosquitoes from different mosquito infections. Note the difference of normally shaped and total sporozoites for concavin(-) parasites. Images show infection of salivary glands. Scale bar: 100 µm",
    "ncbi_link": "GFP: 
concavin: 55152263
concavin: 2655272"
  },
  {
    "caption": "D. Localization of PhiL1-GFP (green) in concavin(-) parasites. Nuclei (blue) stained with Hoechst. Scale bar 5 µm. E. Localization of SiR-Tubulin (red) in concavin(-) parasites. Nuclei (blue) stained with Hoechst. Scale bar 5 µm. F. Localization of CSP (red) in concavin(-) parasites. Nuclei (blue) stained with Hoechst. Scale bar 5 µm. Data information: Asterisks in D-F indicate apical part of the sporozoite.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "A. Growth curve of blood  stage parasites in C57BL/6 mice infected by the bite  of 10 mosquitoes (left) or 10.000 sporozoites intra venously (right) at two different times post mosquito infection as indicated. Shown is the mean ± SEM. Mice infected with Concavin(-) parasites by bite represent 2 independent biological replicates with 3 mice each. Wild type bite back and Concavin(-) intra venous injections represent one biological replicate using 3 or 4 mice respectively.",
    "ncbi_link": "Concavin: 55152263"
  },
  {
    "caption": "C. Liver cell invasion assay  of concavin-gfp and concavin(-) parasites. Parasites are positively stained for CSP in case they remain extracellular. Both, normal and deformed parasites were detected intracellularly. Graph shows quantification of CSP positive (red, hence extracellular) and negative (grey, hence intracellular) sporozoites. Small graph shows the percentage of deformed and normally shaped intracellular concavin(-) sporozoites. Data points represent the 4 individual biological replicates with n indicating the numbers of sporozoites observed. Shown is the mean ± SEM. P-values are calculated using the Mann Whitney test. Scale bar: 5 µm.",
    "ncbi_link": "gfp: 
concavin: 55152263"
  },
  {
    "caption": "D. Liver-stage development of concavin(-) parasites compared to wildtype, both expressing cytoplasmic GFP (white). Parasite size was measured 24h and 48h post infection. Data points represent individual parasites from 4 independent biological replicates. Shown is the mean ± SEM. P-values calculated using the Mann Whitney test. Scale bar: 5 µm.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "E. Sporozoite ejection of immobilized concavin(-) infected mosquitoes on glass slides and quantification of ejected sporozoites from 20 mosquitoes. * indicates individual sporozoites in the ejected saliva. Scale bar: 10 µm.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "F, G. Only normally shaped concavin(-) sporozoites  released by salivary glands  move on helical paths (arrows) through polyacrylamide gels that mimic the skin (F). Quantification of two individual experiments Scale bar 10 µm. (G): only normal shaped sporozoites were able to migrate through the gel.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "A. Percentage of mosquitoes depositing WT or concavin(-) sporozoites in the skin of a mouse during a bite (left) and sporozoites deposited during a mosquito bite (right). P-values are calculated using the Fishers exact test (left) and the Mann Whitney test (right). Bite transmission experiments were repeated over 3 independent mosquito infections for the KO and 2 independent mosquito infections for the WT. For each mosquito infection 2-3 mice were imaged, for a total of 3-5 ears.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "B. Maximum fluorescence intensity projections encoded by color for time from movies showing migrating sporozoites after mosquito-bite transmission. Graphs and camembert diagrams below show fraction of motile and immotile sporozoites after 10, 20 and 30 minutes of recording, numbers analysed as well as sporozoite speed. Pooled data from 4-5 WT or 5-8 concavin (-) bite sites per time point. Scale bar: 50 µm. P-values are calculated using the Mann Whitney test.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "C. Motile WT or concavin(-) sporozoites entering  blood vessels during the first hour following micro-injection. Number above bars shows numbers of sporozoites observed. Pooled data from four WT or five concavin(-) experiments. P-values are calculated using the Fishers exact test.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "D, E (D) Deformation  and (E) disintegration  of concavin(-) sporozoites migrating in the skin. Individual images corresponding to the frames shown on the right are indicated in distinct colours in the maximum projection (left) of 13-min movies. Arrowheads indicate constrictions of the parasites. Graphs below time-lapse  show that deformation and disintegration are preceded by a decrease in speed. Color of dots correspond to the time-points  displayed in the time-lapse images. Scale bars: 10 µm.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "F. Percentage of deformation and disintegration events observed in 54 WT and 57 concavin(-) sporozoites that were tracked for at least 10 min. Pooled data from 5 WT or 10 concavin(-) bite sites.",
    "ncbi_link": "concavin: 55152263"
  },
  {
    "caption": "a, Impairment of two ATG-conjugation systems (Atg12 and LC3) in the Atg7-deficient brain. Brain homogenates from P28 mice were immunoblotted with antibodies against Atg7, Atg5 and LC3. Actin was used as a loading control. Data shown are representative of three separate experiments.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "b, Kaplan-Meier survival curves of Atg7flox/+; nestin-Cre (n = 41) and Atg7flox/flox; nestin-Cre (n = 26) mice over 28 weeks.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "c, Abnormal limb-clasping reflexes in Atg7flox/flox; nestin-Cre mice at P28. When lifted by the tail, Atg7flox/+; nestin-Cre mice behave normally, extending their hind limbs and bodies. In contrast, Atg7flox/flox; nestin-Cre mice bend their legs towards their trunk or tighten their back limbs to their bodies and anterior limbs.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "d, Movement ataxia in Atg7flox/flox; nestin-Cre mice at P28. Motor coordination was tested using a rotarod assay. Atg7flox/+; nestin-Cre (n = 5) and Atg7flox/flox; nestin-Cre (n = 5) mice were placed on a rod rotating at 20 r.p.m., and the time spent on the rod was counted. Data show mean ± s.d. *, P 0.01 (Students t-test). There was no significant sex difference in survival rate and onset-stage of abnormal mice-clasping and tremor in miceflox/flox; nestin-Cre mice.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "a-f, Histological analyses of Atg7flox/+; nestin-Cre (left) and Atg7flox/flox; nestin-Cre (right) cerebral cortex at P56. Cryosections were stained with HE (a-d) or immunostained for the glial marker GFAP (e, f). Boxed areas in a and b are magnified in c and d, respectively. Arrows in c point to large pyramidal neurons in the cerebral cortex.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "g-j, Histological analysis of Atg7flox/+; nestin-Cre (left) and Atg7flox/flox; nestin-Cre (right) cerebellum at P56. Cryosections were stained with HE (g, h) or immunostained for the Purkinje marker calbindin (i, j). Arrows in g and h indicate cerebellar Purkinje cells.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "k-p, TUNEL staining of the cerebral cortex (k, l) and cerebellum (n, o) at P56 in Atg7flox/+; nestin-Cre (k, n) and Atg7flox/flox; nestin-Cre (l, o) sections. TUNEL-positive cells are indicated with arrows and shown as higher magnification images beneath panels l, n and o. Histograms show the average number (± s.d.) of TUNEL-positive cells in ten sections for three animals of each genotype (m, p). *, P 0.05 (t-test). Scale bars, 1 mm (a, b), 100 µm (c-j), 250 µm (k, l, n, o). We observed no sex difference in brain morphology or neuronal loss in Atg7flox/flox; nestin-Cre mice.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "a-l, The presence of ubiquitin-positive dots was examined by immunohistochemistry in several regions including cerebral cortex (a, b), cerebellum (c, d), hippocampus (e, f), hypothalamus (g, h), amygdala (i, j) and pontine nuclei (k, l) of Atg7flox/+; nestin-Cre and Atg7flox/flox; nestin-Cre mice. Note the presence of numerous ubiquitin dots in the amygdala and hypothalamus of the representative mutants. Scale bars, 50 µm.",
    "ncbi_link": "Cre: 
Atg7: 74244
nestin: 18008"
  },
  {
    "caption": "m, n, Electron micrographs of the brain of Atg7flox/flox; nestin-Cre mice. Inclusion bodies (arrows) were often observed in Atg7flox/flox; nestin-Cre hypothalamus. The boxed region in m is shown in n. Inclusion bodies were not detected in Atg7flox/+; nestin-Cre brain (data not shown). Scale bars, 5 µm (m), 1 µm (n). o, Immunoelectron micrograph of ubiquitin in a representative Atg7flox/flox; nestin-Cre hypothalamus. N, nucleus. Scale bar, 1 µm.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "p, q, Immunohistochemical detection of ubiquitin-positive inclusions in the cerebral cortex (p) and hypothalamus (q) at P9, P18 and P56. Brain sections of each genotype at the indicated ages were immunostained with an anti-ubiquitin antibody. Ubiquitin-positive inclusions appeared at P18 and became larger with ageing in the brain of Atg7flox/flox; nestin-Cre mice. Scale bars, 50 µm.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "a, Increase in ubiquitinated proteins in Atg7flox/flox; nestin-Cre mouse brain over time. Homogenates of P9, P18 and P56 brains from Atg7flox/+; nestin-Cre and Atg7flox/flox; nestin-Cre mice were immunoblotted with an anti-ubiquitin antibody. An anti-actin antibody was used as a loading control. Data shown are representative of three separate experiments. We observed no sex difference in the accumulation of ubiquitin in Atg7flox/flox; nestin-Cre mice.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "b, Peptide hydrolysis activity of 20S and 26Sproteasomes. Homogenates from P28Atg7flox/+; nestin-Cre (blue) and Atg7flox/flox; nestin-Cre (pink) brains were fractionated by glyceroldensity gradient centrifugation (10-40% glycerol from fraction 1 to fraction 30). Aliquots from each fraction were used for the assay of chymotryptic activity of proteasomes using Suc-LLVY-AMC as a substrate in the absence (top) or presence (bottom) of 0.05% SDS. The sedimenting positions of 20S and 26Sproteasomes are indicated with arrowheads. Note that whereas 26Sproteasomes exist in active forms in tissues, 20Sproteasomes are latent and are activated artificially by a low concentration of SDS.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "c, ATP-dependent degradation of [35S]-labelled ODC. Degradation of [35S]-labelled ODC was assayed using crude extracts from P28 Atg7flox/+; nestin-Cre and Atg7flox/flox; nestin-Cre brains. The experiment was repeated three times, and values represent mean ± s.d. In the above assays, there were no significant differences between Atg7flox/+; nestin-Cre and Atg7flox/flox; nestin-Cre mice.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "d, Immunoblot analysis of 26S proteasome components. Homogenates from P28 Atg7flox/flox, Atg7flox/+; nestin-Cre and Atg7flox/flox; nestin-Cre brains were immunoblotted with antibodies against the indicated proteins. Data shown are representative of three separate experiments. There was no change in proteasome status for the different genotypes.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(C-G) Resembling the phenotype caused by Notch overexpression (D) or dSir2 mutation (E), HP1c knockdown (F) and mutant (G) flies also exhibit supernumerary anterior scutellar (aSC) bristles on the notum, as indicated by the enlarged views in the left bottom panes. Scale bars, 100 μm.",
    "ncbi_link": "HP1c: 42696
Notch: 31293
dSir2: 42414"
  },
  {
    "caption": "(H-M) Compared with control flies (H and K), HP1c knockdown (J) and mutant (M) flies exhibit an ectopic vein at the distal of L4 and L5 (arrows) and a broken posterior cross vein (arrowhead), which is similar to the phenotype caused by Notch overexpression (I) and dSir2 mutant (L). Scale bars, 500 μm.",
    "ncbi_link": "HP1c: 42696
Notch: 31293
dSir2: 42414"
  },
  {
    "caption": "(A-D) The posterior midguts of 10-day-old control (A), HP1c knockdown (B), HP1c null mutant (C) and HP1c overexpression flies (D). Arrows mark ISCs, arrowheads mark ee cells, circles mark ISC-EB, EB-EB or ISC-ISC nests. ISCs were visualized with esg-GFP alone, EBs were stained with both esg-GFP and Su(H)-lacZ, while ee cells were labeled by Pros and DNA was marked by DAPI. Scale bars, 30 μm.",
    "ncbi_link": "HP1c: 42696"
  },
  {
    "caption": "(A-D) Compared with the control (A) flies, posterior midguts of Notch OE flies exhibit decreased ISCs and ee cells (B), while HP1c OE flies show increased ISCs and ee cells (C), and the phenotype of Notch OE can be rescued by HP1c OE (D). Arrows mark ISCs, arrowheads mark ee cells, circles mark ISC-ISC, ISC-EB or EB-EB nests. ISCs were visualized with esg-GFP alone, EBs were stained with both esg-GFP and Su(H)-lacZ, while ee cells were labeled by Pros and DNA was marked by DAPI. Scale bars, 30 μm.",
    "ncbi_link": "HP1c: 42696
Notch: 31293"
  },
  {
    "caption": "ChIP-qPCR results show the association of HP1c with Notch target genes compared to RFP control. The amount of immunoprecipitated DNA in each sample is represented as signal relative to the total amount of input chromatin (equivalent to 1). Error bars indicate SEM. n=3 technical replicates. Data are evaluated with two-tailed Student's t-test (*p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "Notch: 31293"
  },
  {
    "caption": "(B) RT-qPCR analysis determined the expression of Notch target genes when HP1c was depleted (n=3 technical replicates,, mean ± s.d.). Data are evaluated with two-tailed Student's t-test (*p < 0.05, ***p < 0.001).",
    "ncbi_link": "HP1c: 42696
Notch: 31293"
  },
  {
    "caption": "NRE-GFP signals of S2 cells carrying NICD OE, Hairless KD, Su(H) KD, dSir2 KD and HP1c KD , and the statistical results (F) (n=4 biological replicates, mean ± s.d.). Data are evaluated with two-tailed Student's t-test (*p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "Hairless: 42445
HP1c: 42696
NICD: 31293
dSir2: 42414
Su(H): 34881"
  },
  {
    "caption": "(B) The relative binding of HP1c with Notch target genes when Su(H) KD using ChIP-qPCR analysis (n=3 technical replicates, mean ± s.d.). Data are evaluated with two-tailed Student's t-test (*p < 0.05, **p < 0.01). (C) The relative binding of HP1c on Notch target genes when NICD OE using ChIP-qPCR analysis. (n=3 technical replicates, mean ± s.d.). Data are evaluated with two-tailed Student's t-test (***p < 0.001). ",
    "ncbi_link": "NICD: 31293
Notch: 31293
Su(H): 34881"
  },
  {
    "caption": "Expression level of Shox2, Tbx15, HoxC8, and HoxC5, mRNA was compared using quantitative real-time PCR (qPCR) of RNA isolated from different fat depots. Two subcutaneous depots (inguinal and scapular white), three intra-abdominal fat depots (perigonadal, perirenal, and mesenteric), and interscapular brown adipose tissue of 8 week-old male C57BL/6 mice. Data are shown as mean ± SEM of six samples. Expression level of Shox2, Tbx15, HoxC8, and HoxC5, mRNA was compared using qPCR of RNA isolated from cultured stromovascular cells derived from adipose tissue of the Immortomouse™. The depot-specific cell lines were made from inguinal, scapular white, perigonadal, perirenal, mesenteric, and interscapular brown adipose tissue of 8 week-old male mice. Data are shown as mean ± SEM of cell lines from three individual mice.",
    "ncbi_link": "HoxC5: 15424
HoxC8: 15426
Shox2: 20429
Tbx15: 21384"
  },
  {
    "caption": "qPCR analysis for adiponectin (Adipoq), peroxisome proliferator-activated receptor gamma (Pparγ2), and fatty acid synthase (FAS) in RNA isolated from depot-derived cell lines after in vitro differentiation. Data are shown as mean ± SEM of 3 cell lines/group.",
    "ncbi_link": "adiponectin: 11450
Adipoq: 11450
FAS: 14104
fatty acid synthase: 14104
peroxisome proliferator-activated receptor gamma: 19016
Pparγ2: 19016"
  },
  {
    "caption": "Expression of Wt1, leucine rich repeat neuronal 4 (Lrrn4), Uroplakin 3b (Upk3b), in Immortomouse clonal cell line clusters as preadipocytes (d0) and during six days of adipogenic differentiation.",
    "ncbi_link": "Lrrn4: 320974
leucine rich repeat neuronal 4: 320974
Upk3b: 100647
Uroplakin 3b: 100647
Wt1: 22431"
  },
  {
    "caption": "Expression of Tagln, connective tissue growth factor (Ctgf), Keratin 19 (Krt19), Mx1, caspase 1 (Casp1), and C-X-C Motif Chemokine Ligand 12 (Cxcl12) in Immortomouse clonal cell line clusters as preadipocytes (d0) and during six days of adipogenic differentiation.",
    "ncbi_link": "Casp1: 12362
caspase 1: 12362
Ctgf: 14219
connective tissue growth factor: 14219
Cxcl12: 20315
C-X-C Motif Chemokine Ligand 12: 20315
Krt19: 16669
Keratin 19: 16669
Mx1: 17857
Tagln: 21345"
  },
  {
    "caption": "Expression of Wt1, Lrrn4, Upk3b, Tagln, Ctgf, Krt19, Mx1, Casp1, and Cxcl12 in primary preadipocytes isolated from white adipose tissue of 5-6 month old Wt1-creERT2;Rosa26mT/mG, Tagln-cre;Rosa26mT/mG, and Mx1-cre;Rosa26mT/mG male mice. mGFP and mTomato positive preadipocytes were isolated from the pooled visceral fat depots (perigonadal, perirenal, mesenteric, and pericardial) of Wt1-creERT2;Rosa26mT/mG mice, the pooled subcutaneous fat depots (subcutaneous and scapular white) of Mx1-cre;Rosa26mT/mG, and both the pooled visceral (Tagln-V) and subcutaneous depots (Tagln-S) from Tagln-cre;Rosa26mT/mG mice. Data are shown as mean ± SEM of 4-6 mice/group.",
    "ncbi_link": "Casp1: 12362
Ctgf: 14219
cre: 2777477
Cxcl12: 20315
Rosa26: 14910
Krt19: 16669
Lrrn4: 320974
Mx1: 17857
Tagln: 21345
Upk3b: 100647
Wt1: 22431"
  },
  {
    "caption": "Number of mGFP and mTomato positive preadipocytes isolated by FACS from the indicated white adipose depots from 5-6 month old male Wt1-creERT2;Rosa26mT/mG, Tagln-cre;Rosa26mT/mG, and Mx1-cre;Rosa26mT/mG mice. Data are shown as mean ± SEM of 4-9 mice.",
    "ncbi_link": "cre: 2777477
Rosa26: 14910
Mx1: 17857
Tagln: 21345
Wt1: 22431"
  },
  {
    "caption": "Representative images of whole-mount preparations of the indicated white adipose tissue depots of 5-6 month old Wt1-creERT2;Rosa26mT/mG, Tagln-cre;Rosa26mT/mG, and Mx1-cre;Rosa26mT/mG male mice. The photographs were taken at 10x magnification. Scale bar = 100 μm.",
    "ncbi_link": "cre: 2777477
Rosa26: 14910
Mx1: 17857
Tagln: 21345
Wt1: 22431"
  },
  {
    "caption": "Quantitation of mGFP and mTomato positive adipocytes from each of the indicated white adipose depots from 5-6 month old male Wt1-creERT2;Rosa26mT/mG, Tagln-cre;Rosa26mT/mG, and Mx1-cre;Rosa26mT/mG mice. Adipocytes were counted from four non-overlapping images per depot per mouse.",
    "ncbi_link": "cre: 2777477
Rosa26: 14910
Mx1: 17857
Tagln: 21345
Wt1: 22431"
  },
  {
    "caption": "Number of mGFP positive preadipocytes isolated by FACS from each of the indicated white adipose depots from 5-6 month-old Wt1-creERT2, Tagln-cre, and Mx1-cre crossed to Rosa26mT/mG mice from the experiment shown in Figure 6B. Data are shown as mean ± SEM of 4-9 mice.",
    "ncbi_link": "cre: 2777477
Rosa26: 14910
Mx1: 17857
Tagln: 21345
Wt1: 22431"
  },
  {
    "caption": "Number of mGFP positive adipocytes from each of the indicated white adipose depots from 5-6 month-old Wt1-creERT2, Tagln-cre, and Mx1-cre crossed to Rosa26mT/mG mice. Four separate non-overlapping images/depot/mouse from the experiment shown in Figure 6C. Data are shown as mean ± SEM of 4-9 mice.",
    "ncbi_link": "cre: 2777477
Rosa26: 14910
Mx1: 17857
Tagln: 21345
Wt1: 22431"
  },
  {
    "caption": "(a) Wild-type (WT), atg17Δ, atg7Δ and atg19Δ strains containing RPL25-GFP were grown to mid log phase, starved in SD-N for 48 hours and examined under a fluorescence microscope (left panel). The arrows indicate vacuolar accumulation of the GFP signal. CVT, cytoplasm-to-vacuole-targeting pathway. After the times indicated, at least 100 cells per sample were scored for the presence of Rpl25p-GFP in the vacuole (right panel). Scale bar, 5 μm.",
    "ncbi_link": "atg17: 851142
atg19: 854072
atg7: 856576
RPL25: 853993"
  },
  {
    "caption": "(b) Wild-type and atg7Δ strains containing RPL25-GFP or GFP-ATG8 were grown and starved as in a. Samples were taken at indicated time points and GFP cleavage was analysed by western blotting.",
    "ncbi_link": "atg7: 856576
ATG8: 852200
RPL25: 853993"
  },
  {
    "caption": "(c) The levels of endogenous Rps3p (top) and Rpl3p (middle) were analysed by immunblotting in wild-type and atg7Δ cells. Ponceau staining (bottom) controlled for equal loading. Uncropped images of blots are shown in Supplementary Information, Fig. S6. Starv, starvation.",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(d) Wild-type and pep4Δ cells expressing RPL25-GFP were analysed as in b; 0.1 mM of PMSF was added to pep4Δ cells at the time of starvation to block all vacuolar proteases completely. The LI-COR imaging system was used to quantify the ratio between cleaved GFP and full-length protein as described in Methods. The last time point of wild-type cells containing RPL25-GFP was set to 1 arbitrary unit (a.u.). One of two independent experiments is shown.",
    "ncbi_link": "pep4: 855949
RPL25: 853993"
  },
  {
    "caption": "(e) Wild-type cells containing either RPL25-GFP or control GFP (HOG1-GFP) were analysed as in d. The average of four independent experiments is shown, and the standard deviation was less than 10% (Supplementary Information, Table S3).",
    "ncbi_link": "HOG1: 850803
RPL25: 853993"
  },
  {
    "caption": "(a) Wild-type, ubp3Δ or bre5Δ strains containing RPL25-GFP and either a control plasmid (pRS315), or plasmids expressing Ubp3p or catalytically inactive Ubp3p-C469A from the endogenous promoter, were grown and starved as described in Fig. 1a. Cells were revealed by phase contrast (right), and the localization of Rpl25p-GFP was analysed by GFP microscopy (left). At least 100 cells per sample were analysed. Scale bar, 5 μm.",
    "ncbi_link": "pRS315: 
bre5: 855787
RPL25: 853993
ubp3: 856895
Ubp3p: 856895"
  },
  {
    "caption": "(b) Ribosomes from wild-type and ubp3Δ cells grown as indicated for 16 h under rich or starvation (Starv) conditions were enriched through a high-salt cushion (pellet) and the levels of endogenous Rpl3p were analysed by immunoblotting. Ponceau staining of the blot revealed the total amount of proteins (bottom panel). Uncropped images of blots are shown in Supplementary Information, Fig. S6.",
    "ncbi_link": "ubp3: 856895"
  },
  {
    "caption": "c) Wild-type and ubp3Δ strains containing RPL25-GFP were grown and starved as in Fig. 1a, and GFP cleavage was analysed by western blotting at the times indicated (hours).",
    "ncbi_link": "RPL25: 853993
ubp3: 856895"
  },
  {
    "caption": "(d, e) GFP cleavage of Rpl25p-GFP was analysed in wild-type, ubp3Δ, atg9Δ and bre5Δ strains containing the indicated plasmids, and quantified at the times indicated as described in Fig. 1d. One of three representative experiments is shown for d. The average of three independent experiments is shown in e, and the statistical analysis showed that the standard deviation was less than 13% (Supplementary Information, Table S3).",
    "ncbi_link": "atg9: 851406
bre5: 855787
ubp3: 856895"
  },
  {
    "caption": "(a) The vacuolar localization of GFP-Atg8p was analysed in more than 100 wild-type, ubp3Δ, bre5Δ and atg7Δ cells containing GFP-ATG8 after 10-15 h of nitrogen starvation (right panel). Corresponding GFP and phase contrast images of representative cells are shown in the left panel.",
    "ncbi_link": "atg7: 856576
ATG8: 852200
bre5: 855787
ubp3: 856895"
  },
  {
    "caption": "(c) Wild-type, ubp3Δ and bre5Δ strains containing APE1-RFP were analysed by RFP microscopy (left) and phase contrast (right) 15 h after nitrogen starvation. Scale bars, 5 μm.",
    "ncbi_link": "APE1: 853758
bre5: 855787
ubp3: 856895"
  },
  {
    "caption": "(a) Wild-type, ubp3Δ or bre5Δ strains containing either a control plasmid (pRS315) or plasmids expressing Ubp3p or catalytically inactive Ubp3p-C469A from the endogenous promoter were spotted in serial dilutions onto YPD plates with (left) or without (right) 5 nM rapamycin. The plates were photographed after 2 days at 30 °C.",
    "ncbi_link": "pRS315: 
bre5: 855787
ubp3: 856895
Ubp3p: 856895"
  },
  {
    "caption": "(b) Induction of a GCN4-LacZ reporter was measured 0, 2 and 4 h after amino-acid starvation, and is plotted as Miller units.",
    "ncbi_link": "GCN4: 856709"
  },
  {
    "caption": "(c) Polysome profiles of exponentially growing wild-type and ubp3Δ cells were determined in rich medium or 3 h after nitrogen starvation. The arrows mark the 60S peak.",
    "ncbi_link": "ubp3: 856895"
  },
  {
    "caption": "(d) Wild-type, atg7Δ and ubp3Δ cells containing either RPL25-GFP, control GFP (HOG1-GFP) or RPS2-GFP were analysed as in Fig. 1c. One of three representative experiments is shown.",
    "ncbi_link": "atg7: 856576
HOG1: 850803
RPL25: 853993
RPS2: 852754
ubp3: 856895"
  },
  {
    "caption": "(e) Ribosomes and associated proteins were immunopurified from starved wild-type and ubp3Δ cells containing (RPL25-GFP) and (9 × MYC-UBI) as indicated. The GFP immunoprecipitates (IP; left) and total extracts (TCA, right) were analysed by immunoblotting with anti-Myc antibodies to reveal ubiquitinated proteins (top). Ub, ubiquitin. Bottom: immunoblotting with anti-GFP antibodies controls for the presence of Rpl25p-GFP, and anti-Rpl1p antibodies confirm equal loading of the extract. The asterisk marks protein G on the beads recognized by the secondary antibody.",
    "ncbi_link": "UBI: 
RPL25: 853993
ubp3: 856895"
  },
  {
    "caption": "A) Representative nuclear spreads of wild-type pachytene and Rec8−/− pachytene-like spermatocytes. Nuclear spreads were immunostained for SYCP3 and ACA. Magnified views are indicated by dashed areas. Schematic representation on magnified chromosomes represents tightly associated sister-AEs (separated for easier representation) in paired wild-type homologs, and the appearance of two distinguishable/separated sister-AEs once REC8-mediated cohesion is lost in Rec8−/− univalents. Bars, 10 μm in spreads and 1 μm on insets.",
    "ncbi_link": "Rec8: 56739"
  },
  {
    "caption": "B) Representative nuclear spread of zygotene-like Stag3 mutant spermatocytes. Nuclear spreads were immunostained for SYCP3 and ACA. Magnified views are indicated by dashed areas. Schematic representation on magnified univalents represents: separation of sister-AEs (centre) and close association of sister-AEs (right). Bellow: graph showing the percentages of axes with: separation of AEs (dark grey area) and closely associated AEs (light grey area). 414 axes analysed, from 11 nuclei. Bars, 10 μm in spreads and 1 μm on insets.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "C) Magnified views of zygotene-like Stag3 mutant univalents with LSAEs. Nuclear spreads were immunostained for SYCP3 and ACA. Schematic representation indicates sites of LSAEs. Bellow: graph showing the percentages of axes with: LSAEs (red area), extensive separation of AEs (dark grey area) and closely associated AEs (light grey area). 414 axes analysed, from 11 nuclei. Bars, 1 μm.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "D) Representative nuclear spread of zygotene-like Smc1β−/− spermatocytes. Nuclear spreads were immunostained for SYCP3 and ACA. Magnified views are indicated by dashed areas. Schematic representation on magnified univalents represents sites of LSAEs. Bellow: graph showing the percentages of axes with: LSAEs (red area), extensive separation of AEs (dark grey area) and closely associated AEs (light grey area). 404 axes analysed, from 10 nuclei. Bars, 10 μm in spreads and 1 μm on insets.",
    "ncbi_link": "Smc1β: 140557"
  },
  {
    "caption": "E) STED images of representative zygotene-like Stag3 mutant and Smc1β−/− univalents displaying LSAEs. Nuclear spreads were immunostained for SYCP3. Bars, 1μm.",
    "ncbi_link": "Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "F) Graph indicating the inter-axis distances measured in wild-type pachytene bivalents; pachytene-like Rec8−/− and zygotene-like Stag3 mutant and Smc1β−/− univalents. Each measurement in wild-type and Rec8−/− corresponds to the median of 3 distances measured along one homolog (n=60). Each measurement in Stag3 mutant and Smc1β−/− mutant axes correspond to 1 distance measured at sites of local separation of AEs (n=40 and n=20, respectively). Horizontal lines indicate median.",
    "ncbi_link": "Rec8: 56739
Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "G) Graph indicating the inter-axis distances measured at terminally and centrally located sites of LSAEs in zygotene-like Stag3 mutant univalents. Each measurement corresponds to 1 distance measured at terminally (n=20) and centrally (n=20) located sites of local separation of axial elements. Horizontal lines indicate median.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "A) Representative wild-type pachytene bivalents; pachytene-like Rec8−/−, zygotene-like Stag3 mutant and Smc1β−/− univalents. Nuclear spreads were immunostained for SYCP1, SYCP3 and ACA. Filled arrowheads indicate sites of LSAEs with detectable SYCP1. Bars, 1 μm. Bellow: graphs showing the percentages of sites of LSAEs with detectable SC assembly along sister-AEs of Stag3 mutant and Smc1β−/− univalents (n=120 and n=68, respectively).",
    "ncbi_link": "Rec8: 56739
Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "B) Representative zygotene-like Stag3 mutant univalents. Nuclear spreads were immunostained for SYCP3, ACA and: SYCE1, SYCE2 and TEX12. Filled arrowheads indicate SC assembly between sites of LSAEs. Bars, 1 μm",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "C) Quantification of signal distribution within sites of LSAEs, in Stag3 mutant spermatocytes. Signal distribution measured for SYCP3 and: SYCP1, SYCE1, SYCE2 and TEX12. Empty arrowheads indicate signal intensity peaks that correspond to each of the two sister-chromatid axes, filled arrowheads indicate SYCP1 peaks.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "A) Representative zygotene-like Stag3 mutant and Smc1β−/− univalents. Nuclear spreads were immunostained for SYCP3, SYCE1 and REC8. Bellow: graph showing the percentages of Stag3 mutant axes with sites of LSAEs with and without flanking REC8 foci. 78 axes with LSAEs were analysed. Bars, 1 μm.",
    "ncbi_link": "Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "B) Representative pachytene-like Rec8−/−, zygotene-like Stag3 mutant and Smc1β−/− univalents. Nuclear spreads were immunostained for SYCP3, SYCE1 and RAD21L. Bars, 1 μm.",
    "ncbi_link": "Rec8: 56739
Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "C) Representative zygotene-like Stag3 mutant and Smc1β−/− univalents. Nuclear spreads were immunostained for SYCP3, SYCE1 and RAD21. Bars, 1 μm.",
    "ncbi_link": "Smc1β: 140557
Stag3: 50878"
  },
  {
    "caption": "B) Graph indicating the inter-axis distances measured at sites of local separation of axial elements in zygotene-like Stag3 mutant univalents and along pachytene wild-type X-chromosomes. Each measurement in the X-chromosomes corresponds to the median of 3 distances (according to the scheme in figure) (n=54). Each measurement in Stag3 mutant corresponds to 1 distance measured at sites with local separation of axial elements (n=40). Horizontal lines indicate median. p < 0.0001, obtained with two-tailed Mann-Whitney test. Bellow: schematic representation of the XY pair: sister-AEs are coloured in black and grey for easier visualization. Filled arrowhead indicates PAR. Purple bars in scheme indicate regions where inter-axis distances are measured.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "F) Scatterplot comparing inter-REC8 distances along on X-chromosomes with the distances between flanking REC8 foci at sites of LSAEs in the Stag3 mutant. 211 inter-REC8 distances measured along X-chromosomes and 10 distances measured between flanking REC8 foci in Stag3 mutant. Grey area represents 15% of the chromosome axis length. Horizontal lines indicate the median. p < 0.0001, obtained with two-tailed Mann-Whitney test.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "E) Scatterplot comparing the measured inter-REC8 distances on yet-unsynapsed zygotene autosomes, X-chromosomes and sites of LSAEs in Stag3 mutant. Number of inter-REC8 distances for yet-unsynapsed zygotene autosomes, X-chromosomes and sites of local separation of axial elements in Stag3 mutant, n=294, n=211 and n=10, respectively. Horizontal lines indicate the median. p < 0.0001, obtained with two-tailed Mann-Whitney test.",
    "ncbi_link": "Stag3: 50878"
  },
  {
    "caption": "Roughness measurements on R-LPS labeled (green) WT and Δgmd cells. AFM images of whole bacteria and of the separated areas (coloured squares in first images, 0.4 x 0.4 μm2) are shown. The arithmetic roughness Ra is indicated below each area. Scale bars: 1 μm. Quantitative roughness measurement of R-LPS labeled WT and Δgmd cells. The areas with the lower roughness (more regular surfaces) of Δgmd cells were assigned as areas 1. mAb: monoclonal antibody. Ab: antibody. nWT = 13 bacteria. nΔgmd = 7 bacteria. Differences were statistically analyzed by t-test. **P < 0.01. ns: not significant.",
    "ncbi_link": "gmd: "
  },
  {
    "caption": "Adhesion ratio between the Omp2b positive area compared to the Omp2b negative area. Grey dashed line shows ratio = 1 corresponding to homogeneity in surface structure. nWT = 13 bacteria, nΔgmd = 13 bacteria. Statistical analysis with Mann-Whitney U test showed **P < 0.01.",
    "ncbi_link": "gmd: "
  },
  {
    "caption": "Localization of S-LPS (green) in the eFluor-labeled (magenta) inducible rough strain Δgmd plac-gmd possessing the old pole marker PdhS-mCherry (red). The strains Δgmd and Δgmd plac-gmd -IPTG were used as negative controls. Scale bars: 2 μm.",
    "ncbi_link": "gmd: "
  },
  {
    "caption": "Distribution of R-LPS and S-LPS in Δgmd plac-gmd after 3, 6, 9 and 24 h post-induction analyzed by flow cytometry (one representative example among 3 biological replicates, n = 20,000 events).",
    "ncbi_link": "gmd: "
  },
  {
    "caption": "SAGA is epistatic to the TORC1 and TORC2 pathways in the regulation of differentiation in response to nutrient availability. (A,B,D,E) Expression of ste11+ (A,D) using quantitative RT-PCR of RNA extracted from cells grown either in nutrient rich medium (dark gray) or shifted for 4 hours to starvation medium (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, tsc1Η, gcn5Η tsc1Η, tsc2Η, gcn5Η tsc2Η, rhb1-DA4 - a constitutively active (CA) rhb1 mutant [34], gcn5Η rhb1-DA4, tor2-L1310P - a CA tor2 mutant [33], gcn5Η tor2-L1310P, tor1Η, gcn5Η tor1Η, gad8Η, and gcn5Η gad8Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 (A,B)independent experiments, overlaid with individual data points and standard error (SE) bars. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4 for A,B)",
    "ncbi_link": "act1: 2540051
gcn5: 2542513
rhb1: 2540853
ste11: 2540258
tor2: 2540720
tsc1: 2541869
tsc2: 2543339"
  },
  {
    "caption": "SAGA is epistatic to the TORC1 and TORC2 pathways in the regulation of differentiation in response to nutrient availability. (A,B,D,E) Expression of mei2+ (B,E) using quantitative RT-PCR of RNA extracted from cells grown either in nutrient rich medium (dark gray) or shifted for 4 hours to starvation medium (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, tsc1Η, gcn5Η tsc1Η, tsc2Η, gcn5Η tsc2Η, rhb1-DA4 - a constitutively active (CA) rhb1 mutant [34], gcn5Η rhb1-DA4, tor2-L1310P - a CA tor2 mutant [33], gcn5Η tor2-L1310P, tor1Η, gcn5Η tor1Η, gad8Η, and gcn5Η gad8Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 (A,B) independent experiments, overlaid with individual data points and standard error (SE) bars. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4 for A,B)",
    "ncbi_link": "act1: 2540051
gcn5: 2542513
mei2: 2542080
rhb1: 2540853
tor2: 2540720
tsc1: 2541869
tsc2: 2543339"
  },
  {
    "caption": "(C,F) Cells were grown to mid-log phase either in rich medium or shifted for 8 hours to starvation medium. Zygotes and tetrads, which correspond to differentiated cells, were counted under a light microscope. Cells of the following genotypes were analyzed: WT isogenic controls, gcn5Η, tsc1Η, gcn5Η tsc1Η, rhb1-DA4, gcn5Η rhb1-DA4, gad8Η, and gcn5Η gad8Η. Each value represents the mean percentage and SE of differentiating cells to the total number of cells, averaged from 4 independent experiments. At least 200 cells from the indicated genotypes were counted in each experiment. White arrowheads indicate zygotes. Scale bar, 10 μm.",
    "ncbi_link": "gcn5: 2542513
rhb1: 2540853
tsc1: 2541869"
  },
  {
    "caption": "SAGA is epistatic to the TORC1 and TORC2 pathways in the regulation of differentiation in response to nutrient availability. (A,B,D,E) Expression of ste11+ (A,D) using quantitative RT-PCR of RNA extracted from cells grown either in nutrient rich medium (dark gray) or shifted for 4 hours to starvation medium (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, tsc1Η, gcn5Η tsc1Η, tsc2Η, gcn5Η tsc2Η, rhb1-DA4 - a constitutively active (CA) rhb1 mutant [34], gcn5Η rhb1-DA4, tor2-L1310P - a CA tor2 mutant [33], gcn5Η tor2-L1310P, tor1Η, gcn5Η tor1Η, gad8Η, and gcn5Η gad8Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 3 (D,E) independent experiments, overlaid with individual data points and standard error (SE) bars. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 3 for D,E).",
    "ncbi_link": "act1: 2540051
gad8: 2539206
gcn5: 2542513
ste11: 2540258
tor1: 2540473"
  },
  {
    "caption": "SAGA is epistatic to the TORC1 and TORC2 pathways in the regulation of differentiation in response to nutrient availability. (A,B,D,E) Expression of mei2+ (B,E) using quantitative RT-PCR of RNA extracted from cells grown either in nutrient rich medium (dark gray) or shifted for 4 hours to starvation medium (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, tsc1Η, gcn5Η tsc1Η, tsc2Η, gcn5Η tsc2Η, rhb1-DA4 - a constitutively active (CA) rhb1 mutant [34], gcn5Η rhb1-DA4, tor2-L1310P - a CA tor2 mutant [33], gcn5Η tor2-L1310P, tor1Η, gcn5Η tor1Η, gad8Η, and gcn5Η gad8Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 3 (D,E) independent experiments, overlaid with individual data points and standard error (SE) bars. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 3 for D,E).",
    "ncbi_link": "act1: 2540051
gad8: 2539206
gcn5: 2542513
mei2: 2542080
tor1: 2540473"
  },
  {
    "caption": "(C,F) Cells were grown to mid-log phase either in rich medium or shifted for 8 hours to starvation medium. Zygotes and tetrads, which correspond to differentiated cells, were counted under a light microscope. Cells of the following genotypes were analyzed: WT isogenic controls, gcn5Η, tsc1Η, gcn5Η tsc1Η, rhb1-DA4, gcn5Η rhb1-DA4, gad8Η, and gcn5Η gad8Η. Each value represents the mean percentage and SE of differentiating cells to the total number of cells, averaged from 4 independent experiments. At least 200 cells from the indicated genotypes were counted in each experiment. White arrowheads indicate zygotes. Scale bar, 10 μm.",
    "ncbi_link": "gad8: 2539206
gcn5: 2542513"
  },
  {
    "caption": "(A,B) Expression of ste11+ (A) using quantitative RT-PCR of RNA extracted from cells grown either in rich medium (dark gray) or starved for 4 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), ppa2Η, par1Η, pab1Η, tsc1Η, and pab1Η tsc1Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4).",
    "ncbi_link": "act1: 2540051
pab1: 2541519
par1: 2539379
ppa2: 2540072
ste11: 2540258
tsc1: 2541869"
  },
  {
    "caption": "(A,B) Expression of mei2+ (B) using quantitative RT-PCR of RNA extracted from cells grown either in rich medium (dark gray) or starved for 4 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), ppa2Η, par1Η, pab1Η, tsc1Η, and pab1Η tsc1Η. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4).",
    "ncbi_link": "act1: 2540051
mei2: 2542080
pab1: 2541519
par1: 2539379
ppa2: 2540072
tsc1: 2541869"
  },
  {
    "caption": "(D) P-Taf12 was followed by anti-FLAG IB of protein extracts from WT and pab1Η strains, grown in rich conditions (R) or starved for 45 minutes (S). An anti-Rpb1 IB is shown as a control for loading. The signal intensities of P-Taf12 and total Taf12 were quantified in each strain and condition. Ratios of P-Taf12 to total Taf12 were calculated from 6 independent experiments and individually plotted in a graph below the IBs, together with the mean and SE. Averaged values from all WT controls grown in rich medium were set at 1 to allow comparisons across culture conditions and strains. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 6; *p < 0.01; #p < 0.05). A short and a long exposure of the FLAG IB are shown to detect total Taf12 and P-Taf12, respectively, within the linear range of the chemi-luminescence signal.",
    "ncbi_link": "pab1: 2541519"
  },
  {
    "caption": "(G) P-Taf12 was followed by anti-FLAG IB of protein extracts from WT and tor2-ts10 strains, grown in rich conditions at 25°C or shifted to 30°C for 4 and 6 hours. (F,G) Anti-tubulin IBs are shown as a control for loading between samples. Shown are IBs that are representative of 3 independent experiments. The star (*) symbol labels unspecific bands detected by the anti-FLAG or anti-CBP antibodies in S. pombe.",
    "ncbi_link": "tor2: 2540720"
  },
  {
    "caption": "(A) Igo1 phosphorylation (P-Igo1) was followed by anti-MYC IB of protein extracts from WT, ppk18Η, and igo1-S64A strains, grown in rich conditions (R) or starved for 45 minutes (S). Igo1 migration was analyzed by electrophoresis of both a 12% SDS-polyacrylamide gel containing the Phos-tag™ molecule (right panel) and a standard 10% SDS-polyacrylamide gel (left panel). Arrowheads indicate the various phosphorylated isoforms of Igo1-MYC in each strain and condition. Shown is an IB representative of 2 independent experiments.",
    "ncbi_link": "ppk18: 3361535"
  },
  {
    "caption": "(B,C) Expression of ste11+ (C) using quantitative RT-PCR of RNA extracted from cells grown either in rich medium (dark gray) or starved for 4 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, pab1Η, gcn5Η ppk18Η, pab1Η, pab1Η ppk18Η, igo1Η, igo1-S64A, gcn5Η igo1-S64A and pab1Η igo1-S64A. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4).",
    "ncbi_link": "act1: 2540051
gcn5: 2542513
igo1: 2542961
pab1: 2541519
ppk18: 3361535
ste11: 2540258"
  },
  {
    "caption": "(B,C) Expression of mei2+ (D) using igo1 of RNA extracted from cells grown either in rich medium (dark gray) or starved for 4 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), gcn5Η, ppk18Η, gcn5Η ppk18Η, pab1Η, pab1Η ppk18Η, igo1Η, igo1-S64A, gcn5Η igo1-S64A and pab1Η igo1-S64A. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 4 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 4).",
    "ncbi_link": "act1: 2540051
gcn5: 2542513
mei2: 2542080
igo1: 2542961
pab1: 2541519
ppk18: 3361535"
  },
  {
    "caption": "(D) P-Taf12 was followed by anti-FLAG IB of protein extracts from WT, S. pombeΗ, and igo1Η strains, grown in rich conditions (R) or starved for 45 minutes (S). An anti-MYC IB is shown as a control for loading. (D,E) The signal intensities of P-Taf12 and total Taf12 were quantified in each strain and condition. Shown below each blot are average measurements of 3 independent experiments (n = 3). A short and a long exposure of the FLAG IB are shown to detect total Taf12 and P-Taf12, respectively, within the linear range of the chemi-luminescence signal. The star (*) symbol labels an unspecific band detected by the FLAG antibody in S. pombe.",
    "ncbi_link": "igo1: 2542961
ppk18: 3361535"
  },
  {
    "caption": "(E) P-Taf12 was followed in WT, igoS64A, pab1Η, and pab1Η igoS64A strains, grown in rich conditions (R) or starved for 45 minutes (S). An anti-Rpb1 IB is shown as a control for loading. (D,E) The signal intensities of P-Taf12 and total Taf12 were quantified in each strain and condition. Shown below each blot are average measurements of 3 independent experiments (n = 3). A short and a long exposure of the FLAG IB are shown to detect total Taf12 and P-Taf12, respectively, within the linear range of the chemi-luminescence signal. The star (*) symbol labels an unspecific band detected by the S. pombe antibody in S. pombe.",
    "ncbi_link": "pab1: 2541519"
  },
  {
    "caption": "(A) P-Taf12 was followed by anti-FLAG IB of protein extracts from WT, tor1Η, and gad8Η strains, grown in rich conditions (R) or starved for 45 minutes (S). An anti-tubulin IB is shown as a control for loading. The signal intensities of P-Taf12 and total Taf12 were quantified in each strain and condition. P-Taf12 to Taf2 ratios were calculated from 3 independent experiments and individually plotted in a graph below the IBs, together with the mean and SE. Averaged values from all WT controls grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 3).",
    "ncbi_link": "gad8: 2539206
tor1: 2540473"
  },
  {
    "caption": "(B) P-Taf12 was followed by anti-FLAG IB of protein extracts from sty1Η cells (left panel) or ssp2Η cells (right panel), grown in rich conditions (R) or starved for 45 minutes (S). An anti-tubulin IB is shown as a control for loading. The star (*) symbols label an unspecific band detected by the anti-FLAG antibody in S. pombe. Shown are IBs that are representative of 2 independent experiments.",
    "ncbi_link": "ssp2: 2539109
sty1: 2541652"
  },
  {
    "caption": "(A,B) Expression of quantitative RT-PCR+ (A) using quantitative RT-PCR of RNA extracted from cells grown either in rich medium (dark gray) or starved for 2 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT) and taf12-5A mutants. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 6 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 6).",
    "ncbi_link": "taf12: 
act1: 2540051
ste11: 2540258"
  },
  {
    "caption": "mei2+ (B) using quantitative RT-PCR of RNA extracted from cells grown either in rich medium (dark gray) or starved for 2 hours (light grey). Cells of the following genotypes were analyzed: wild-type isogenic controls (WT) and taf12-5A mutants. act1+ served as a control for normalization across samples. Values from a WT strain grown in rich medium were set at 1 to allow comparisons across culture conditions and mutant strains. Each column represents the mean value of 6 independent experiments, overlaid with individual data points and SE. Statistical significance was determined by 2-way ANOVA followed by Bonferroni's multiple comparison tests (n = 6).",
    "ncbi_link": "act1: 2540051
mei2: 2542080
taf12: 2542785"
  },
  {
    "caption": "(C,E) Zygotes and tetrads, which correspond to differentiated cells, were counted from cultures of homothallic cells grown to mid-log phase in rich medium (t0) and shifted to starvation medium for up to 24 hours (C) Cells of the following genotypes were analyzed: wild-type isogenic controls (WT), taf12-5A, taf12-5DE, tor1-1972A, and taf12-5A tor1-1972A. Each value represents the mean percentage and SE of differentiating cells to the total number of cells, averaged from 6 independent experiments. At least 200 cells from the indicated genotypes were counted in each experiment. Statistical significance was determined by 2-way ANOVA followed by Tukey's multiple comparison tests (n = 6).",
    "ncbi_link": "taf12: 2542785"
  },
  {
    "caption": "B, C Serial transplantations of PR+/+ and PR−/− mammary epithelia. (B) Fluorescence stereo microscopy of third‐generation mammary outgrowths derived from 8‐week‐old PR+/+; EGFP and PR−/−; EGFP donor mice. (C) Table summarizing 3 independent serial transplant experiments with PR+/+; EGFP and PR−/−; EGFP. Each engrafted gland is represented by a micrograph; black sectors represent area of fat pad filled by engrafted epithelium. Scale bar: 200 μm.",
    "ncbi_link": "PR: 18667"
  },
  {
    "caption": "D, E Serial transplantation of RANKL+/+ and RANKL−/− mammary epithelia. (D) Fluorescence stereo microscopy of third‐generation mammary outgrowths derived from 5‐week‐old RANKL+/+; EGFP and RANKL−/−; EGFP donor mice. Insets: higher magnification showing side branches present in the WT control (arrowheads) absent from RANKL−/−; EGFP epithelium. (E) Table summarizing three independent serial transplant experiments with RANKL+/+; EGFP and RANKL−/−; EGFP donor mice. Scale bar: 200 μm.",
    "ncbi_link": "RANKL: 21943"
  },
  {
    "caption": "F, G Serial transplantation of Wnt4+/+ and Wnt4−/− mammary epithelia. (F) Fluorescence stereo microscopy of third‐generation mammary outgrowths derived from mammary buds of E12.5 and E13.5 Wnt4+/+; EGFP and Wnt4−/−; EGFP embryos. Scale bar: 200 μm. (G) Table summarizing three independent serial transplant experiments with Wnt4+/+; EGFP donor mice. Scale bar: 200 μm.",
    "ncbi_link": "Wnt4: 22417"
  },
  {
    "caption": "A Epifluorescence stereo microscopy of inguinal mammary gland from a 5‐day‐old Wnt4::Cre; mT/mG female (n = 7). Scale bars: 0.5 mm and 0.1 mm (inset).",
    "ncbi_link": "Cre: 
Wnt4: 22417"
  },
  {
    "caption": "B, C Histology sections of mammary glands from a 5‐day‐old (B; n = 7) and a 10‐day‐old (C; n = 5) Wnt4::Cre; mT/mG female stained by double immunofluorescence microscopy for EGFP (green) and PR (magenta, not detected), counterstained with DAPI (blue). Scale bar: 50 mm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "D-F EGFP (green) and PR (magenta) co‐immunofluorescence microscopy counterstained with DAPI (blue) on histology sections from mT/mG; Wnt4::Cre mammary glands at different developmental stages. (D) TEB of a 4‐week‐old female (n = 4); scale bar: 30 μm. (E) Ducts of an 8‐week‐old female (n = 3); scale bar: 100 μm; inset, scale bar: 20 μm. (F) Duct of a female at day 10.5 of pregnancy (n = 3); scale bar: 150 μm; inset, scale bar: 30 μm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "G-I EGFP (green), PR (magenta), and p63 (white) triple co‐immunofluorescence microscopy counterstained with DAPI (blue) on histological sections from mT/mG; Wnt4::Cre mammary glands at different developmental stages. (G) Ducts of 5‐day‐old female (n = 3). (H) TEB of a 4‐week‐old female (n = 3). (I) Duct of an 8‐week‐old female (n = 3). Scale bars: 30 μm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "J-O Epifluorescence stereo microscopy of mammary glands harvested from 15‐day‐old Wnt4::GFP females either WT (n = 18) (J, M), ERα−/− (n = 4) (K, N), or PR−/− (n = 3) (L, O). dTomato expression (J-L); EGFP expression (M-O) is not abrogated in ERα−/− nor PR−/− epithelia. Arrowheads mark the main duct originating from the nipple. Scale bar: 50 μm.",
    "ncbi_link": "ERα: 13982
PR: 18667"
  },
  {
    "caption": "Q Bar plots showing relative PR and Wnt4 mRNA expression normalized to CK18 mRNA in mammary organoids from 5 pubertal (6 weeks old) and 3 adult (11 weeks old) mice exposed for 6 h to vehicle (C), 17β‐estradiol (20 nmol) (E2), or R5020 (20 nmol) (P). Bars represent the mean ± SD of 3 independent experiments.",
    "ncbi_link": "CK18: 
PR: 18667
Wnt4: 22417"
  },
  {
    "caption": "R-X Epifluorescence stereo microscopy of contralateral mammary glands that were engrafted with Wnt4::GFP epithelium from 8‐week‐old females, either PRWT (R, T, V, X) or PR−/− (S, U, W). dTomato expression (R, S); EGFP expression (T, U) double epifluorescence (V, W, X) on contralateral engrafted glands 3 weeks after surgery when recipients were 6 weeks old. Representative result from three independent experiments. Arrowheads point to TEBs (V, X) or to origin of growth (W). Scale bar (R-W): 5 mm, (X): 1 mm.",
    "ncbi_link": "PR: 18667"
  },
  {
    "caption": "A-D Representative epifluorescence stereo microscopy of inguinal mammary glands from a 10‐day‐old mT/mG (A, C) and MMTV::Cre; mT/mG (B, D) female (n = 7). Scale bar: 1 mm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "E Higher magnification of inguinal mammary gland from a 10‐day‐old MMTV::Cre; mT/mG female. Scale bar: 0.2 mm.F Immunofluorescence microscopy for EGFP (green) on a mammary gland section from a 10‐day‐old MMTV::Cre; mT/mG female counterstained with DAPI (blue) (n = 7). Scale bar: 30 μm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "G Epifluorescence stereo microscopy of mammary glands from 10‐day‐old littermates either MMTV::Cre; mT/mG Wnt4fl/+ or MMTV::Cre; mT/mG; Wnt4fl/fl. Scale bar: 1 mm. Arrowhead marks the main duct originating from the nipple.H Bar plot showing ratio of branching points in prepubertal Cre+;Wnt4fl/fl (n = 12) relative to Cre+;Wnt4fl/+ littermates (n = 10). Two‐tailed, paired Student's t‐test was used to calculate statistical significance.",
    "ncbi_link": "Cre: 
Wnt4: 22417"
  },
  {
    "caption": "I Fluorescence stereo microscopy of mammary glands from 35‐day‐old littermates either MMTV::Cre; mT/m; Wnt4fl/+ or MMTV::Cre; mT/m;Wnt4fl/fl. Note ductal elongation is delayed in Wnt4‐deficient mammary epithelium compared to Wnt4fl/+ control. LN: lymph node. Scale bar: 4 mm.J, K Bar plots showing number of terminal end buds (TEBs) (J) and area of mammary fat pad filled by the ductal system (K). Ctrl (Wnt4fl/wt or Wnt4fl/fl; Cre−): n = 6, fl/+; Cre+: n = 4, and fl/fl; Cre+: n = 7). Data are presented as the mean ± SD. Two‐tailed Student's t‐test was used to calculate statistical significance.",
    "ncbi_link": "Cre: 
Wnt4: 22417"
  },
  {
    "caption": "L, M Bar plots showing BrdU incorporation index in inguinal mammary glands of 4‐week‐old Wnt4fl/+; Cre+ (n = 3) or Wnt4fl/fl; Cre+ (n = 4) in the ducts (L) and in the TEBs (M). Data are presented as the mean ± SD. Two‐tailed Student's t‐test was used to calculate statistical significance.",
    "ncbi_link": "Wnt4: 22417"
  },
  {
    "caption": "A Whole‐mount microscopy of X‐gal‐stained Axin2+/lacZ in E12.5 embryo showing β‐galactosidase expression in the mammary buds (arrows) (n = 8). Scale bar: 1 mm. Arrowheads mark mammary buds.",
    "ncbi_link": "lacZ: 
Axin2: 12006"
  },
  {
    "caption": "B-F Whole‐mount microscopy of X‐gal (blue)‐ and carmine alum (red)‐stained mammary glands harvested from Axin2+/lacZ mice at distinct developmental stages. (B) At postnatal day 1, β‐galactosidase activity detected in the nipple area (n = 6). Scale bar: 1 mm. (C, D) In 5‐week‐old mammary glands, reporter activity was detected around the ducts (small arrows) and in the neck region of the terminal end buds (TEBs) (large arrows) (C) (n = 8). Scale bars: 400 μm (C) and 100 μm (D). (E) At 8.5 day of pregnancy, reporter expression was detected in the ducts. Higher magnification (inset) suggests myoepithelial expression (n = 10). Scale bar: 1 mm. (F) Whole‐mount at day 14.5 of pregnancy: reporter activity is limited to ducts (n = 5). Scale bar: 200 μm.",
    "ncbi_link": "lacZ: 
Axin2: 12006"
  },
  {
    "caption": "G Histology section of Axin2::LacZ mammary gland at day 8.5 of pregnancy counterstained with nuclear red; luminal epithelial cells show no detectable β‐galactosidase activity but myoepithelial cells do. Scale bar: 200 μm.",
    "ncbi_link": "LacZ: 
Axin2: 12006"
  },
  {
    "caption": "I Representative whole‐mount stereo microscopy of X‐gal (blue)‐ and carmine alum (magenta)‐stained mammary gland biopsies taken from 14‐week‐old Axin2::LacZ females collected at diestrus and estrus, respectively (n = 3). Scale bar: 200 μm.",
    "ncbi_link": "LacZ: 
Axin2: 12006"
  },
  {
    "caption": "J Relative Wnt4 and Axin2 mRNA expression in mammary glands from three mice in estrus versus diestrus assessed by semiquantitative qRT-PCR normalized to 18S rRNA. Two‐tailed, paired Student's t‐test was used to calculate statistical significance.",
    "ncbi_link": "18S: 
Axin2: 12006
Wnt4: 22417"
  },
  {
    "caption": "K Stereo microscopy of X‐gal‐ and carmine alum‐stained mammary glands from ovariectomized Axin2::LacZ females treated for 72 h with vehicle (n = 4) (left), 17‐β‐estradiol (E2) (n = 6) (center), 17‐β‐estradiol and progesterone (E2 and P) (n = 8) (right). Scale bar: 200 μm.",
    "ncbi_link": "LacZ: 
Axin2: 12006"
  },
  {
    "caption": "L, M Stereo microscopy of contralateral glands whole‐mounted and X‐gal stained after engraftment with mammary buds from Axin2::LacZ transgenic and Wnt4+/+ or Wnt4−/− female E12.5 and E13.5 embryos (L) or Axin2::LacZ transgenic and either PR+/− or PR−/− 8‐week‐old females (M), at day 8.5 of pregnancy. β‐galactosidase expression reflecting Axin2 transcription is readily detected in PR+/− as well as Wnt4+/+ mammary epithelia but not in the PR−/− (n = 6) and Wnt4−/− counterparts (n = 6). Blue: X‐gal staining; magenta: carmine alum counterstain. Scale bars: 200 μm.",
    "ncbi_link": "LacZ: 
Axin2: 12006
PR: 18667
Wnt4: 22417"
  },
  {
    "caption": "A X‐gal‐stained whole‐mounts of Axin2::LacZ embryos at E14.5 either Wnt4+/+or Wnt4−/− (n = 5 or 4, respectively). Arrows mark mammary buds. Scale bar: 5 mm.",
    "ncbi_link": "LacZ: 
Axin2: 12006
Wnt4: 22417"
  },
  {
    "caption": "B Whole‐mount analysis of X‐gal‐ and carmine alum‐stained mammary glands harvested from 6‐week‐old littermates either Wnt4fl/wt;MMTV::Cre+;Axin2+/lacZ (n = 5) or Wnt4fl/flMMTV::Cre+;Axin2+/lacZ (n = 4). Left insets: higher magnification; right insets: histology section of the same gland. Note expression of reporter detected around the neck of TEBs in Wnt4‐deficient and littermate control is comparable. LN, lymph node. Scale bars: 1 mm, and inset scale bar: 100 μm.",
    "ncbi_link": "Cre: 
Axin2: 12006
Wnt4: 22417"
  },
  {
    "caption": "A/B. Hybrid Rab7/Arl8b compartment. A. Representative confocal images of fixed HeLa cells expressing Arl8b-GFP (green), immunolabeled against endogenous Rab7 (eRab7, magenta). Zoom insets (3x) highlight select regions of colocalization (white), white arrowheads point to vesicles positive for both GTPases. B. Colocalization (Mander's overlap) of endogenous Rab7 with Arl8b-GFP versus free GFP (EV), n EV=4, n Arl8b=9 images (3≥ cells per image) analysed from 2 independent experiments. Significance: 2-tailed student's t-test, * p<0.05.",
    "ncbi_link": "GFP: 
Arl8b: 55207"
  },
  {
    "caption": "C-F. Analysis of Arl8b compartment organization and dynamics as a function of Rab7 activity status. C. Left and middle panels: representative confocal images of live HeLa cells expressing mCherry-Rab7 or its mutants Q67L and T22N (white), together with Arl8b-GFP (green), taken at the start of time-lapse (t0). Right panels: tracks followed by Arl8b-positive null during the time-lapse lasting 50 s recorded at 0.5 s per frame, with highest displacement rates for each track depicted on a rainbow colour scale (blue: immobile; red: maximum mobility per time interval). Zoom insets (2.8x) highlight select peripheral (PP) and perinuclear (PN) cell regions D. Plot of Arl8b-positive pixel distribution expressed as fractional distance along a straight line from center of nucleus (0) to the plasma membrane (1.0), numbers of (pixels) plotted given above each scatter, n=7 cells analysed per condition from 2 independent experiments. E/F. Quantification of mean Arl8b vesicle displacement and maximum speed, respectively, n Rab7=21, n QL=25, n TN=24 images (3≥ cells per image) analysed from 2 independent experiments.",
    "ncbi_link": "GFP: 
mCherry: 
Arl8b: 55207
Rab7: 7879"
  },
  {
    "caption": "A-D. Correlative light and electron microscopy (CLEM) on A. untransfected (WT) HeLa cells harbouring endogenous CD63 labeled with GFP as compared to those ectopically expressing B. HA-RILP, C. HA-SKIP or D. both HA-RILP and HA-SKIP. Left panels: wide field fluorescence images of fixed cells showing endogenous GFP-CD63 (green) and SiR-lysosome-stained endosomes and/or lysosomes (red). Cell and nuclear boundaries are demarcated with solid and dashed lines respectively, zoom insets highlight regions selected for EM imaging. Middle panels: overview electron micrographs of perinuclear (PN) and peripheral (PP) cell regions selected for further analysis. Various endolysosomal subtypes are designated by arrowheads: MVBs (white), lysosomes (black), endolysosomes (yellow) and abnormal/enlarged endolysosomes (red). Right panels: graphical representations of endosomal distribution under the indicated conditions based on ultrastructural characterization.",
    "ncbi_link": "HA: 
SKIP: 23207
RILP: 83547"
  },
  {
    "caption": " B. Co-immunoprecipitations (Co-IP) of HA-RILP and RFP-SKIP with GFP-Rab7 (R7) versus its mutants Q67L (QL) and T22N (TN) from HEK293T cells using GFP-trap beads. Representative immunoblots against GFP, HA and RFP are shown, EV: empty vector, IP: immunoprecipitation, TL: total lysate (see also Fig EV1E). C. Quantification of interaction between SKIP and Rab7 mutants expressed as fraction Co-IP relative to wild type Rab7, n=3 independent experiments. ",
    "ncbi_link": "Rab7: 478945///404007"
  },
  {
    "caption": " E. In vitro glutathione precipitation assays. E. SKIP truncation analysis by PD against GST-Rab7. Top panels: representative immunoblots against Myc and GST (see also Fig EV1G). Bottom panels: schematic representation of SKIP domain organization. Regions of SKIP capable of interacting with Arl8b versus Rab7 are demarcated with solid black lines. An alignment of human (h) and murine (m) SKIP sequences to known effectors of Rab7 surrounding the conserved KML/I effector motif at residues 610-612 of SKIP is provided. H. Graphical summary of SKIP as a dual effector of Arl8b and Rab7. ",
    "ncbi_link": "SKIP: 23207"
  },
  {
    "caption": " F/G. Co-IP of RFP-SKIP versus its KMI motif mutants AAI and AAA with constitutively active GFP-Rab7 Q67L using RFP-trap beads (see also Fig EV1H). F. Representative immunoblots against GFP and RFP. G. Quantification of interaction between SKIP mutants with Rab7 expressed as fraction Co-IP relative to wild type SKIP, n=3 independent experiments. ",
    "ncbi_link": "SKIP: 23207"
  },
  {
    "caption": "I-K. Time-lapse of SKIP-mediated transport of late endosomes. I. Schematic representation of tamoxifen-induced activation of SKIP onto endosomal membranes. J/K. Live HeLa cells co-expressing GFP-ER-SKIP (green) and mCherry-Rab7 (magenta) together with HA-RILP (unstained) expressed at low levels (cells transfected at 1:5 RILP:SKIP ratio) were imaged in the J. absence or K. presence of tamoxifen, allowing on-demand association of SKIP with endosomal membranes. Confocal frames from time-lapses taken at the indicated time-points following treatment are shown. Cell and nuclear boundaries are demarcated with solid and dashed lines respectively, zoom insets (3x) highlight select peripheral (PP) and perinuclear (PN) cell regions, scale bars: 10µm",
    "ncbi_link": "GFP: 
HA: 
SKIP: 23207
RILP: 83547"
  },
  {
    "caption": "A-C. Consequences of effector depletion on the endogenous Arl8b/Rab7 hybrid compartment. A. Representative confocal images of fixed HeLa cells harbouring GFP-tagged endogenous Arl8b (G-eArl8b, green), transfected with the indicated siRNAs and immunolabeled against endogenous Rab7 (eRab7, magenta). B. Colocalization (Mander's overlap) between endogenous Arl8b and Rab7 in response to effector depletion, n siC=10, n siRILP=9, n siSKIP=9 images (4≥ cells per image) analysed from 2 independent experiments. C. Immunoblot analysis for depletion efficiency of SKIP and RILP, with actin as loading control.",
    "ncbi_link": "SKIP: 23207
RILP: 83547"
  },
  {
    "caption": "D/E. Effect of Rab7 GTPase activity status on its association with the peripheral SKIP compartment. D. Left panels: Representative confocal images of fixed HeLa cells expressing GFP-Rab7 or its mutants Q67L or T22N (green) together with HA-RILP (red) and Myc-SKIP (blue), immunolabeled against the indicated epitope tags. Right panels: Schematic overview per condition. E. Colocalization (Mander's overlap) between the indicated protein pairs, n Rab7=5, n QL=5, n TN=7 images (2≥ cells per image) analysed from 2 independent experiments. F. Graphical summary of Rab7 removal from the SKIP compartment. ",
    "ncbi_link": "GFP: 
Rab7: 478945"
  },
  {
    "caption": "B. Representative confocal images of fixed HeLa cells depleted of TBC1D2, 1D5, or 1D15 using siRNA oligo pools and immunolabeled against CD63 (white), scale bar: 10µm. C. Plot of CD63 pixel distribution as a function of TBC1D2/1D5/1D15 depletion expressed as fractional distance along a straight line from center of nucleus (0) to the plasma membrane (1.0), number of (pixels) plotted given above each scatter, n≥8 cells per condition analysed from 2 independent experiments.",
    "ncbi_link": "1D15: 64786
TBC1D2: 55357
1D5: 9779"
  },
  {
    "caption": "D/E. Rescue of TBC1D15 depletion phenotype. D. Representative confocal images of fixed HeLa cells transfected with either control siRNA (siC) or oligo #3 targeting TBC1D15 (siTBC1D15) and ectopically expressing either GFP-EV, GFP-TBC1D5 or siRNA-resistant GFP-TBC1D15res (green), immunolabeled for CD63 (magenta), scale bar: 10µm. E. Quantification of rescue expressed as % cells (average) in the population exhibiting one of 3 phenotypes: clustered, dispersed or intermediate; total numbers of cells analysed per condition appear above each bar, n=3 independent experiments.",
    "ncbi_link": "GFP: 
TBC1D15: 64786
TBC1D5: 9779"
  },
  {
    "caption": "Effects of TBC1D15 depletion on the morphology and dynamics of late organelles. F. Representative electron micrographs of fixed HeLa cells transfected with either control siRNA (siC) or a pool of oligos targeting TBC1D15 (siTBC1D15) are shown, scale bars as indicated.",
    "ncbi_link": "TBC1D15: 64786"
  },
  {
    "caption": "G. Analysis of late compartment dynamics as a function of TBC1D15 depletion. Tracks followed by SiR-lysosome-positive vesicles during a time-lapse lasting 255 sec (5 s per frame), with highest displacement rates for each track depicted on a rainbow colour scale (blue: immobile; red: maximum mobility per time interval). Zoom insets (3x) highlight select peripheral (PP) and perinuclear (PN) regions, scale bar: 10µm EV10). H. Quantification of high motility fraction (% tracks with displacement rates above 0.9µm/sec), n siC=27, n si1D15=37 images (2≥ cells per image) analysed from 2 independent experiments. Effectiveness of TBC1D15 (si1D15) depletion is confirmed by immunoblot against endogenous TBC1D15 (e1D15) following its immunoprecipitation (IP), TL: total lysate.",
    "ncbi_link": "1D15: 64786
TBC1D15: 64786"
  },
  {
    "caption": "I. FRAP of GFP-Rab7 in live HeLa cells transfected with either control siRNA (siC, black line) or a pool of oligos targeting TBC1D15 (si1D15, red line). Plotted is average GFP-Rab7 signal recovery during 200 s following bleaching, expressed as % of pre-bleach signal, n=3 bleach regions per sample.",
    "ncbi_link": "1D15: 64786
TBC1D15: 64786"
  },
  {
    "caption": "Effects of depleting known GAPs for Rab7 on late compartment segregation mediated by RILP and SKIP. A. Representative confocal images of fixed HeLa cells transfected with either control siRNA (siC), two different siRNA oligos targeting TBC1D15 (#1 and #3) or oligo pool targeting TBC1D17 and ectopically expressing GFP-Arl8b (green) in combination with HA-RILP (cyan) and Myc-SKIP (red), immunolabeled against endogenous Rab7 (eRab7, magenta) and the indicated epitope tags. Cell and nuclear boundaries are demarcated with solid and dashed lines respectively, zoom insets (3.5x) highlight select peripheral (PP) and perinuclear (PN) cell regions, scale bar: 10µm. ",
    "ncbi_link": "TBC1D15: 64786
TBC1D17: 79735"
  },
  {
    "caption": "E. Effect of TBC1D15 depletion on Rab7-dependent MHC-II receptor trafficking to the SKIP-positive compartment, n siC=21, n si1D15=21 cells analysed from 3 independent experiments",
    "ncbi_link": "1D15: 64786
TBC1D15: 64786"
  },
  {
    "caption": "Representative confocal images of either control (siC) Hela cells harbouring endogenous TBC1D15 tagged with GFP (Ge1D15, green) or those depleted of FIS1 using a pool of siRNA oligos, fixed and immunolabeled for the mitochondrial marker TOM20 (blue) in combination with either endogenous A. Rab7 Zoom insets (2.5x) highlight select cell regions, arrowheads point to vesicles positive for TBC1D15 and negative for TOM20 (yellow).",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "Representative confocal images of either control (siC) Hela cells harbouring endogenous TBC1D15 tagged with GFP (Ge1D15, green) or those depleted of FIS1 using a pool of siRNA oligos, fixed and immunolabeled for the mitochondrial marker TOM20 (blue) in combination with either endogenous B. CD63 (red). Zoom insets (2.5x) highlight select cell regions, arrowheads point to vesicles positive for TBC1D15 and negative for TOM20 (yellow).",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "Effect of FIS1 on late compartment distribution. C. Representative confocal images of fixed HeLa cells depleted of FIS1 using a siRNA oligo pool and immunolabeled against CD63 (white).",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "D. Plot of CD63 pixel distribution as a function of FIS1 depletion expressed as fractional distance along a straight line from center of nucleus (0) to the plasma membrane (1.0), number of (pixels) plotted given above each scatter, n siC=14, n siFis1=17 cells analysed from 2 independent experiments.",
    "ncbi_link": "FIS1: 51024
Fis1: 51024"
  },
  {
    "caption": "E. Colocalization of SKIP with endogenous Rab7 (Mander's overlap) in response to FIS1 depletion, n siC=13, n siFis1=9 images (3≥ cells per image) analysed from 2 independent experiments",
    "ncbi_link": "FIS1: 51024
Fis1: 51024"
  },
  {
    "caption": "F. Validation of FIS1 depletion efficiency assayed by qPCR and expressed as fraction FIS1 mRNA remaining relative to siC, n=3 independent experiments.",
    "ncbi_link": "FIS1: 51024"
  },
  {
    "caption": "G-J. Recruitment of endogenous TBC1D15 to the SKIP compartment. G. Left panels: representative confocal images of fixed HeLa cells harbouring endogenous TBC1D15 tagged with GFP (G-e1D15, green) and ectopically expressing either empty vector, HA-SKIP or PLEKHM1-HA (red), immunolabeled against HA. Zoom insets (2.7x) highlight select peripheral (PP) and perinuclear (PN) cell regions. Right panels: pixel plots of endogenous GFP-TBC1D15 (green line) and HA signals (red line) corresponding to the dashed white lines in G. H-J. Colocalization (Mander's overlap) between the indicated pairs of proteins, n≥5 images, 3≥ cells per image, analysed per condition from 2 independent experiments",
    "ncbi_link": "HA: 
PLEKHM1: 9842
SKIP: 23207"
  },
  {
    "caption": "Effects of SKIP KMI motif on HOPS complex recruitment. A. Analysis of SKIP/HOPS interactions by co-IP of RFP/mCherry-HOPS subunits with Myc-SKIP versus the KMI motif mutant AAA from HEK293T cells using RFP-trap beads. Representative immunoblots against RFP and Myc are shown, IP: immunoprecipitation, TL: total lysate. B. Quantification of SKIP/HOPS interactions, n=3 independent experiments. Top graph: fold change in binding of HOPS subunits to AAA mutant relative to wild type (WT) SKIP (1.0), significance: one-way ANOVA test (relative to VPS41). Bottom graph: Co-IP per HOPS subunit relative to VPS39, significance: one-way ANOVA test (relative to VPS39), * p<0.05, *** p<0.001, ns: not significant.",
    "ncbi_link": "SKIP: 23207"
  },
  {
    "caption": "D. Representative confocal images of fixed HeLa cells ectopically expressing Myc-SKIP, KMI motif mutant (AAA) or RUN domain truncation mutant (∆RUN) (red) together with RFP-VPS39 (green), immunolabeled for endogenous VPS11 (eVPS11, blue).",
    "ncbi_link": "Myc: 
SKIP: 23207"
  },
  {
    "caption": "Effect of HOPS over-expression on recruitment of TBC1D15 to the SKIP compartment. E. Representative confocal images of fixed HeLa cells harbouring endogenous GFP-TBC1D15 (Ge1D15, green) and ectopically expressing HA-SKIP (red) together with mCh-VPS18 or RFP-VPS39 (white), immunolabeled for endogenous VPS18 or VPS11 (blue), as indicated",
    "ncbi_link": "mCh: 
RFP: 
VPS18: 57617
VPS39: 23339"
  },
  {
    "caption": "F-I. Colocalization of SKIP and HOPS complex with TBC1D15 as a function of HOPS subunit over-expression. F/H. Mander's overlap between F. SKIP or H. eVPS18 and endogenous TBC1D15, n≥5 images (2≥ cells per image) analysed per condition from 2 independent experiments, significance: one-way ANOVA test (relative to EV), ** p<0.01, *** p<0.001, ns: not significant. G/I. Mander's overlap between G. SKIP or I. eVPS11 and endogenous TBC1D15 as a function VPS18 overabundance, with or without FIS1 depletion (siFIS1), n≥3 images (2≥ cells per image) analysed per condition from 2 or more independent experiments.",
    "ncbi_link": "FIS1: 51024
VPS18: 57617"
  },
  {
    "caption": "A/B. In situ SKIP/TBC1D15 complex formation assayed using proximity-based biotin ligation (BioID). A. Neutravidin precipitates (PD) from biotin-treated HEK293T cells ectopically expressing GFP-TBC1D15 (GFP-1D15) together with HA-BioID-SKIP or HA-BioID-EV. Representative immunoblots against GFP, HA and VPS18 , TL: total lysate. B. Quantification of biotinylation of GFP-TBC1D15 (top graph) and endogenous VPS18 (eVPS18, bottom graph) by BioID-SKIP, expressed relative to BioID-EV (1.0), n=4 independent experiments.",
    "ncbi_link": "GFP: 
HA: 
SKIP: 23207
1D15: 66687
TBC1D15: 64786"
  },
  {
    "caption": "C. Analysis of TBC1D15/HOPS interactions by co-IP of RFP/mCherry-HOPS subunits with GFP-TBC1D15 from HEK293T cells using GFP-trap beads. Left panel: schematic of HOPS complex composition, with subunits tested marked in yellow. Right panel: representative immunoblots against GFP and RFP; IP: immunoprecipitation, TL: total lysate.",
    "ncbi_link": "TBC1D15: 66687"
  },
  {
    "caption": "Effects of VPS18 depletion on the recruitment of TBC1D15 to the SKIP complex. D. Representative confocal images of fixed HeLa cells harbouring endogenous GFP-TBC1D15 (G-e1D15, green), transfected with either control siRNA (siC) or oligo pool targeting VPS18 (siVPS18) and ectopically expressing HA-SKIP (red), immunolabeled against endogenous VPS18 (eVPS18, blue) and HA, scale bar: 10µm. Cell and nuclear boundaries are demarcated with solid and dashed lines respectively, zoom insets (3.5x) highlight select peripheral (PP) and perinuclear (PN) cell regions. E. Colocalization (Mander's overlap) between SKIP and endogenous TBC1D15 as a function of VPS18 depletion, n siC=9, n siVPS18=11 images (2≥ cells per image) analysed from 2 independent experiments.",
    "ncbi_link": "VPS18: 57617"
  },
  {
    "caption": "F. Neutravidin precipitates (PD) from biotin-treated HeLa cells ectopically expressing GFP-TBC1D15 (GFP-1D15) together with BioID-SKIP or BioID-EV. Representative immunoblots against GFP, HA and VPS18 are shown, TL: total lysate. G. Quantification of GFP-TBC1D15 biotinylation by BioID-SKIP over BioID-EV in response to VPS18 depletion expressed as % of control (siC), n=4 independent experiments performed in HeLa or HEK293T cells. H. Quantification of VPS18 protein abundance from experiments in G, n=4.",
    "ncbi_link": "SKIP: 23207
VPS18: 57617"
  },
  {
    "caption": ". Effect of TBC1D15 activity on Rab7 displacement from the SKIP compartment. Colocalization (Mander's overlap) between Rab7 and TBC1D15 (WT or R417A mutant) in the presence of either SKIP or PLEKHM1 combined with the indicated VPS proteins, n≥ 5 images (2≥ cells per image) analysed from 2 independent experiments",
    "ncbi_link": "PLEKHM1: 9842
SKIP: 23207
TBC1D15: 64786"
  },
  {
    "caption": "B HCT116  and SW480  cells with GDH1  knockdown were incubated under normoxia  and hypoxia, respectively. Then, cell viability  was assessed by trypan blue staining. (n=3). Data information: Data are mean ± SD from the biological replicates (B Statistics: two-way ANOVA with Tukey's HSD post hoc test (B)",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "F HIF1A  gene transcription was slightly impaired after GDH1  depletion. The cells in Figure 1B were collected after incubation under normoxia  or hypoxia, and the HIF1A  mRNA level was analysed via quantitative real-time PCR (qRT‒PCR). (n=3; ns, not significant). Data information: Data are mean ± SD from the biological replicates Statistics: unpaired two-tailed student's t-test",
    "ncbi_link": "GDH1: 2746
HIF1A: 3091"
  },
  {
    "caption": "H Tumour formation study. HCT116-shNT and HCT116-shGDH1 cells were injected into the  left groin  of nude mice. Solid tumours were stained  with an antibody against Ki67  (Scale bars: 50 μm). (n=3) (H). Data information: Data are mean ± SD from the biological replicates Statistics: unpaired two-tailed student's t-test",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "(E) H&E staining  of colon cancer tumours from GDH1IEC+/+ and GDH1IEC-/- mice  (scale bar, 200 μm). F F4/80 staining  in a noninflamed portion of the colon  after AMO/DSS  treatment (scale bar, 50 μm). G ZO-1 staining  in colon  sections of mice  treated with sequential AMO/DSS  treatment (scale bar, 200 μm).",
    "ncbi_link": "GDH1: 14661"
  },
  {
    "caption": "I Survival  percentages of  GDH1IEC+/+ mice  (n=11) and GDH1IEC-/- mice  (n=9) during progression of the inflammatory cancer  switch. Data information: Statistics: log-rank test (I).",
    "ncbi_link": "GDH1: 14661"
  },
  {
    "caption": "K Both HIF1α  protein levels and AMPK  activity were assessed in the intestine  of  GDH1IEC-/- mice  after AOM/DSS  treatment using the indicated antibodies.",
    "ncbi_link": "GDH1: 14661"
  },
  {
    "caption": "E HCT116  or SW480  cells containing WT or GDH1  with K503/K527R mutations were incubated under normoxia  and hypoxia, respectively. GDH1-FLAG  was enriched, and an antibody against pan-lysine acetylation  was used to test GDH1-lysine acetylation.",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "H GDH1-depleted cell lines were constructed and then rescued with the expression of wild-type GDH1  or K503/K527R mutant GDH1.",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "F HCT116  or SW480  cells were depleted of endogenous GDH1  and rescued with SFB-tagged rGDH1 WT, K503Q or K503R. rGDH1-SFB  proteins were enriched using M2-FLAG  beads to determine the Vmax  of αKG  production (F). (n=3). Data information: Data are mean ± SD from the biological replicates Statistics: one-way ANOVA with Tukey's HSD post hoc test",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "A, B Immunoblot  of the HIF1α   protein level under hypoxia  for 6 hours when enzymes related to the αKG  level were overexpressed in cells, including GDH1  (A). Relative αKG  levels in contrast to the control (B). (n=3). Data information: Data are mean ± SD from the biological replicates (B Statistics: one-way ANOVA with Tukey's HSD post hoc test (B",
    "ncbi_link": "GDH1: 2746"
  },
  {
    "caption": "I EGLN1  activity test. His-GDH1  with K503 or K527 acetylation  (AcK503 or AcK527) and mimic acetylation  at K503 or K527 (K503Q or K527Q) were purified from  E. coli. Then, His-GDH1  was incubated for 1 hour with HA-EGLN1(I). EGLN1  activity was tested by converting αKG  to succinate. (n=3). Data information: Data are mean ± SD from the biological replicates Statistics: one-way ANOVA with Tukey's HSD post hoc test",
    "ncbi_link": "His: "
  },
  {
    "caption": "the mRNA expression  levels of the HIF1α  target genes GLUT1, HK1, PGK1  and CCND1  (M) in the indicated cell lines under hypoxia. (n=3). Data information: Data are mean ± SD from the biological replicates Statistics: one-way ANOVA with Tukey's HSD post hoc test",
    "ncbi_link": "CCND1: 595
HK1: 3098
PGK1: 5230
GLUT1: 6513"
  },
  {
    "caption": "P HIF1α  transactivation was examined in the indicated cell lines under hypoxia  with or without treatment with the HIF1α  transactivation inhibitor 2-MeOE2 (1 μM) for 12 hours. (n=3). Data information: Data are mean ± SD from the biological replicates P). Statistics: one-way ANOVA with Tukey's HSD post hoc test , P)",
    "ncbi_link": "HIF1α: 3091"
  },
  {
    "caption": "D, The levels of both AcK503 and AcK527 were analysed when cells were transfected with small interfering RNA (siRNA) targeting TIP60, PCAF, CBP  or p300  (D)",
    "ncbi_link": "CBP: 1387
p300: 2033
PCAF: 8850
TIP60: 10524"
  },
  {
    "caption": "F HCT116  and SW480  cells were transfected with or without FLAG-p300. The p300-associated proteins were enriched with M2-FLAG  beads and subjected to immunoblot  analysis using antibodies against GDH1, GDH1-K503 or GDH1-K527 acetylation.",
    "ncbi_link": "FLAG: 
p300: 2033"
  },
  {
    "caption": "K The HIF1A  gene was transiently knocked down, and HCT116  cells were cotransfected with FLAG-p300  and HA-GDH1  for a Co-IP assay.",
    "ncbi_link": "FLAG: 
HA: 
p300: 2033
GDH1: 2746
HIF1A: 3091"
  },
  {
    "caption": "L EDC-3- and NTL-2-foci lose their specific localization in the vicinity of mitochondria upon genetic inhibition of mrps-5, top: EDC-3-foci, bottom: NTL-2-foci (n=3 independent experiments).",
    "ncbi_link": "mrps-5: 179721"
  },
  {
    "caption": "A Confocal images of young adult animals expressing mitochondria-targeted GFP in body wall muscle cells upon dcap-2 or ntl-2 RNAi treatment (right panels indicate higher magnification images of inlays in left panels; right panel scale bar, 10μm). Images were acquired using a X40 objective lens (n=3 independent experiments).",
    "ncbi_link": "dcap-2: 178321
ntl-2: 173773"
  },
  {
    "caption": "D Quantification of intestinal mitochondrial mass upon knockdown of either dcap-2 or ntl-2, in animals shown in Fig 2B & C. (n=3 independent experiments with at least 30 animals/experiment; ****P< 0.0001; one-way analysis of variance (ANOVA).",
    "ncbi_link": "dcap-2: 178321
ntl-2: 173773"
  },
  {
    "caption": "F Representative images showing the effect of dcap-2 and ntl-2 genetic inhibition on the intestinal cell mitochondrial content in 7-day-old nematodes. (n=3 independent experiments; Images were acquired using a X5 objective lens). G Quantification of the mean GFP fluorescence intensity in the matrix of intestinal mitochondria as shown in Fig 2F (n=3 independent experiments with at least 57 animals/experiment; ****P< 0.0001; one-way analysis of variance (ANOVA)).",
    "ncbi_link": "dcap-2: 178321
ntl-2: 173773"
  },
  {
    "caption": "H Quantification of the mtDNA/nDNA ratio under control conditions and upon genetic inhibition of either dcap-2 or ntl-2 (n=2 independent experiments; ***P< 0.001, *P< 0.05; one-way analysis of variance (ANOVA)).",
    "ncbi_link": "dcap-2: 178321
ntl-2: 173773"
  },
  {
    "caption": "C Measurement of the promoter activity of the SKN-1 target gene gst-4 upon genetic inhibition of either dcap-2 or ntl-2 in wild-type background, daf-2 mutant background and in a mutant background (skn-1(lax120)) where SKN-1 is constitutively active (n=3 independent experiments with at least 256 animals/experiment; ****P< 0.0001; two-way analysis of variance (ANOVA), followed by Turkey's multiple comparison test).",
    "ncbi_link": "daf-2: 175410
dcap-2: 178321
gst-4: 177886
ntl-2: 173773
SKN-1: 177343
skn-1: 177343"
  },
  {
    "caption": "E Relative expression of skn-1 mRNA in wild-type, DCAP-2- and NTL-2- depleted animals (n=4 independent experiments, P(dcap-2(RNAi)) =0.98, P(ntl-2(RNAi))>0.99; one-way analysis of variance (ANOVA)).",
    "ncbi_link": "DCAP-2: 178321
dcap-2: 178321
NTL-2: 173773
ntl-2: 173773
skn-1: 177343"
  },
  {
    "caption": "H Relative expression of aak-2 mRNA in wild-type, DCAP-2- and NTL-2- depleted animals (n=2 independent experiments; P(dcap-2(RNAi)) =0.85, P(ntl-2(RNAi))>0.99; one-way analysis of variance (ANOVA)).",
    "ncbi_link": "aak-2: 181727
DCAP-2: 178321
dcap-2: 178321
NTL-2: 173773
ntl-2: 173773"
  },
  {
    "caption": "D Representative images showing an increase in NTL-2-foci upon dcap-2 genetic inhibition (n=3 independent experiments).",
    "ncbi_link": "dcap-2: 178321"
  },
  {
    "caption": "E Quantification of NTL-2 foci upon dcap-2 genetic inhibition (n=3 independent experiments with at least 40 animals/experiment; ****P<0.0001; two-tailed unpaired t-test).",
    "ncbi_link": "dcap-2: 178321"
  },
  {
    "caption": "F Representative images showing an increase in the signal of DCAP-2-foci upon ntl-2 genetic inhibition. Images were acquired using a X40 objective lens (n=3 independent experiments). G Respective quantification (n=3 independent experiments with at least 80 animals/experiment; ****P<0.0001; two-tailed unpaired t-test).",
    "ncbi_link": "ntl-2: 173773"
  },
  {
    "caption": "L Quantification of the percentage of fluorescence recovery after photobleaching (FRAP) to measure the rates of de novo protein synthesis upon genetic inhibition of either ntl-2 or dcap-2 in 6-day-old-adult animals; the protein synthesis inhibitor cycloheximide (500μM) and let-363 genetic inhibition where used as controls. Measurements started after animals have recovered for 2hrs post photobleaching (n=3 independent experiments with at least 50 animals/experiment).",
    "ncbi_link": "dcap-2: 178321
let-363: 172167
ntl-2: 173773"
  },
  {
    "caption": "A Analysis of expression of select MTPTs by real time quantitative PCR (RT-qPCR) following RNA immunoprecipitation (RIP) in anti-GFP isolates from NTL-2::GFP transgenic animals, unc-119(ed3)III (no GFP expression) and pgst-4GFP (used as an additional negative control) counterparts (n=2 independent experiments, ***P< 0.001; one-way analysis of variance (ANOVA).",
    "ncbi_link": "GFP: 
gst-4: 177886
NTL-2: 173773
unc-119: 176519"
  },
  {
    "caption": "B Representative images showing the localization of NTL-2/storage bodies relative to mitochondria upon genetic inhibition of either tomm-20 or akap-1 (green: NTL-2, red: TMRE, a mitochondrial-membrane potential-dependent dye; n=3 independent experiments). Scale bars, 20 µm. Images were acquired using a X63 objective lens. C Quantification of the distances NTL-2/storage bodies acquire from mitochondria upon genetic inhibition of either tomm-20 or akap-1 (n=3 independent experiments with at least 45 animals/experiment; ***P< 0.001; one-way analysis of variance (ANOVA)).",
    "ncbi_link": "akap-1: 175898
tomm-20: 179691"
  },
  {
    "caption": "E Immunoblot analysis in mitochondria isolates of whole animal extracts showing the protein levels of NTL-2 contained in the isolate in control conditions and upon genetic inhibition of akap-1, tomm-20, mrps-5 and atp-3; genetic inhibition of ntl-2 is used as a control; NTL-2 protein is detected by an anti-GFP antibody in transgenic animals that contain the NTL-2::GFP protein fusion (n=2 independent experiments). F Quantification of NTL-2 protein bound to mitochondria under control conditions and upon genetic inhibitions shown in E; CTC-1 is used as a loading control for mitochondria (n=2 independent experiments; *P<0.05, **P<0.01, ***P<0.001; one-way analysis of variance (ANOVA) followed by Dunnett's test).",
    "ncbi_link": "akap-1: 175898
atp-3: 172195
mrps-5: 179721
ntl-2: 173773
tomm-20: 179691"
  },
  {
    "caption": "A Percent survival of wild-type, DCAP-2- and NTL-2- depleted animals subjected to heat stress for 5 hrs at 37oC and then counted every 24 hours (n=4 independent experiments with at least 294 animals/experiment). B Percent survival of wild-type, DCAP-2- and NTL-2- depleted animals following paraquat (8mM) administration and counted every 24 hours (n=4 independent experiments with at least 144 animals/experiment). C Percent survival of wild-type, DCAP-2- and NTL-2- depleted animals counted every 24 hours post CCCP (15μM) treatment (n=4 independent experiments with at least 116 animals/experiment).",
    "ncbi_link": "DCAP-2: 178321
NTL-2: 173773"
  },
  {
    "caption": "E Knockdown of ntl-2 shortens the lifespan of wild-type animals, while NTL-2 overexpression extends lifespan.",
    "ncbi_link": "ntl-2: 173773
NTL-2: 173773"
  },
  {
    "caption": "A Knockdown of akap-1 extends the lifespan of wild-type animals, while it does not further extend the lifespan of NTL-2 overexpressing animals. B Knockdown of akap-1 reverses the lifespan shortening of ntl-2 mutant worms. C Knockdown of akap-1 ameliorates the lifespan shortening caused by ntl-2 genetic inhibition (double RNAi administered as 1:1 mixture).",
    "ncbi_link": "akap-1: 175898
ntl-2: 173773
NTL-2: 173773"
  },
  {
    "caption": "(C) Fold induction of the fluorescence of CasTA candidates using different gRNAs targeting to different locations of the GFP reporter gene compared to a strain without CasTA. The dCas9-ω was verified in the ∆rpoZ strain background, and the rest of candidates were verified in the wild-type strain (BW25113).",
    "ncbi_link": "GFP: 
rpoZ: 948160"
  },
  {
    "caption": " (E) Different gRNAs were paired with dCas9-AsiA and dCas9-ω to profile the optimal gRNA binding distance. The dCas9-AsiA was verified in the wild-type strain (BW25113), and dCas9-ω was examined in the ∆rpoZ strain background. ",
    "ncbi_link": "rpoZ: 948160"
  },
  {
    "caption": "(A) CasTA2.1 upregulates a genomically inserted GFP reporter.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " (D) Demonstration of multiplexed CRISPRa and CRISPRi using CasTA2.1 on a reporter containing GFP and mScarlet. Parental cells had low basal GFP and high basal mScarlet expression. ",
    "ncbi_link": "GFP: 
mScarlet: "
  },
  {
    "caption": "(C, D Confocal  micrographs of HeLa  cells expressing GFP-TECPR1  and treated with osmotic shock assay or LLOMe  (C), or infected with the bacteria indicated (D) and fixed at 1 h (S. Typhimurium and L. monocytogenes) or 0.5 h (S. flexneri) post-infection. Cells were stained  for Galectin-8 and DNA (DAPI). Scale bar, 20 μm.",
    "ncbi_link": "GFP: 
TECPR1: 25851"
  },
  {
    "caption": "(F) Percentage of bacteria positive for mCherry-TECPR1 in ATG5  knockout (KO) or ATG5-complemented MEF  cells at 1 h (S. Typhimurium) or 0.5 h (S. flexneri) post-infection. Mean +/- SD of four (S. Typhimurium) or two (S. flexneri) independent experiments. n > 100 bacteria per coverslip. (G) Percentage of S. Typhimurium  positive for GFP-TECPR1  at 1 h post-infection  in HeLa  cells pretreated or not with 100 nM Wortmannin. Mean +/- SD of two independent experiments. n > 100 bacteria per coverslip.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "H)  Confocal  micrographs of HeLa  cells expressing GFP-TECPR1  either alone or together with FLAG-tagged neutral sphingomyelinase 2  (nSMase2; (H)) Cells were stained  for Galectin-8  and DNA (DAPI). Scale bar, 20 μm. (I) Percentage of S. Typhimurium positive for GFP-TECPR1  or endogenous Galectin-8  at 1 h post-infection  in HeLa  cells expressing FLAG-nSMase2  or not. Mean +/- SD of two (TECPR1) or three (Gal8) independent experiments. n > 100 bacteria per coverslip.",
    "ncbi_link": "FLAG: 
GFP: 
neutral sphingomyelinase 2: 55512
nSMase2: 55512
TECPR1: 25851"
  },
  {
    "caption": "(E) Confocal  micrographs  of HeLa  cells expressing TECPR1  N' DysF-GFP  with or without FLAG-nSMase2, infected with S. Typhimurium, fixed at 30 min post-infection and stained  with anti-Galectin 8 antibody. DNA stained  with DAPI. Scale bar, 20 μm.",
    "ncbi_link": "FLAG: 
GFP: 
nSMase2: 55512
TECPR1: 25851"
  },
  {
    "caption": "(F) Percentage of S. Typhimurium positive for N' DysF-GFP  in Hela  cells, expressing FLAG-nSMase  or not, fixed at 30 min post-infection. Mean +/- SEM of three independent experiments performed in duplicate.",
    "ncbi_link": "FLAG: 
nSMase: 55512"
  },
  {
    "caption": "(G and H) Confocal  micrographs of HeLa  cells expressing the indicated GFP-tagged DysF  domains, infected with mCherry-S. Typhimurium and fixed at 30 min post-infection (G) or treated with osmotic shock assay, fixed and stained  with anti-Galectin 8 antibody (H). The bottom row in H depicts an enlarged version of the boxed region shown above. Scale bar, 20 μm.",
    "ncbi_link": "GFP: 
mCherry: "
  },
  {
    "caption": "(F) Confocal  micrographs of HeLa  cells expressing either GFP-TECPR1  WT or W154A and treated with LLOMe  or DMSO  vehicle control for 10 min and fixed. Scale bar, 20 μm. (G) Number of GFP-positive puncta per cell were enumerated in samples depicted in (F). Data from 50 cells from a single experiment, representative of two. p value from one-way ANOVA with Tukey's multiple comparisons test.",
    "ncbi_link": "GFP: 
TECPR1: 25851"
  },
  {
    "caption": "(A Confocal  micrographs  of indicated MEF  cell lines infected with mCherry-expressing S. Typhimurium, fixed at 30 min post-infection  and stained  with anti-ATG5  antibody (A) Scale bar, 20 μm.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "C) Confocal  micrographs  of indicated MEF   cell lines infected with mCherry-expressing S. Typhimurium, fixed at 30 min post-infection  and stained  with anti-LC3  antibody (C). Scale bar, 20 μm.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "(F) Confocal  micrographs of either control of ATG16L1-deficient MEF  cells, transfected with either control or TECPR1  siRNA (siRNA no. 66 depicted), infected with mCherry-expressing S. Typhimurium for 30 min, fixed and stained  with anti-LC3  antibody. Scale bar, 20 μm.",
    "ncbi_link": "mCherry: 
ATG16L1: 77040
TECPR1: 70381"
  },
  {
    "caption": "(A) Percentage of S. Typhimurium  positive for  Galectin-8 and/or GFP-TECPR1  in either control Hela  cells or those expressing GFP-TECPR1  at 1 h post-infection. Mean +/- SEM of three independent experiments performed in duplicate. n > 100 bacteria per coverslip. (B) Confocal  micrographs  of HeLa  cells expressing the indicated GFP-TECPR1  constructs or not (control), infected with S. Typhimurium  for 30 min, fixed and stained  with anti-Galectin-8 and DAPI. Scale bar, 20 μm.­­ Arrowheads indicate bacteria positive for Galectin 8, of which more are present in cells expressing GFP-TECPR1  WT but not W154A. Arrow indicates bacterium to which GFP-TECPR1  but not Galectin 8 has been recruited.",
    "ncbi_link": "GFP: 
TECPR1: 25851"
  },
  {
    "caption": "(C) Percentage of S. Typhimurium  positive for  Galectin-8  in Hela  cells expressing the indicated GFP-TECPR1  constructs or not (control) and infected with S. Typhimurium  for 1 h. Mean +/- SEM of five independent experiments performed in triplicate. p value from one-way ANOVA with Tukey's multiple comparisons test.",
    "ncbi_link": "GFP: 
TECPR1: 25851"
  },
  {
    "caption": "(D) Fold intracellular proliferation  of S. Typhimurium  in HeLa  cells expressing the indicated GFP-TECPR1  constructs or not (control) as assessed by  colony forming unit  assay. Mean +/- SEM of four (ΔPH) or five (control, WT, W154A and ΔAIR) independent experiments. p value from one-way ANOVA with Dunnett's multiple comparisons test.",
    "ncbi_link": "GFP: 
TECPR1: 25851"
  },
  {
    "caption": "(B) Kaplan Meier plots of long-term overall survival of H/NSCC patients from the TCGA dataset divided on the basis of high versus low HSD17B7 expression levels relative to its median expression value among males (darkgreen and lightgreen lines) and females (red and orange lines), showing statistically significant association of elevated HSD17B7 expression with poorer patient survival. Statistical significance was calculated by the log-rank test between the groups. High_female: n=57patients. Low_female: n= 79 patients. High_male: n= 203 patients. Low_male: n= 181 patients.",
    "ncbi_link": "HSD17B7: 51478"
  },
  {
    "caption": "(D-F) Intradermal tumorigenicity assays with HKCs (269W) stably infected with an HSD17B7 overexpressing lentivirus (HSD17B7-oe) versus control (Ctrl). Experimental conditions were the same as in Fig 2. Mice were sacrificed 15 days after injection. Shown are representative images and quantification of tumor cells density assessed by immunohistochemical staining with anti-pan keratin antibodies (D,) as well as % of Ki67 positive cells (E) and K1 positivity (F) of pan-keratin positive areas. For (D), n(tumors per condition) = 9; for (E and F) n(3 fields per tumor, 5 tumors per condition) = 15. *p<0.05, ****p<0.0001. Horizontal line: median. 2-tail unpaired t-test. Scale bar: 500μm (D), 100μm (F).",
    "ncbi_link": "HSD17B7: 51478"
  },
  {
    "caption": "(G, H) Intradermal tumorigenicity assays with SCC13 cells overexpressing HSD17B7 (HSD17B7-oe) versus control (Ctrl). Mice were sacrificed 15 days after injection. Shown are representative images and quantification of tumor cells density, assessed by immunohistochemical staining with anti-pan keratin antibodies (G) as well as % of Ki67 positive cells in pan-keratin positive areas (H). For (G), n(tumors per condition) = 4; for (H), n(3-5 fields per tumor, 4 tumors per condition) 15, 19. *p<0.05; Horizontal line: median. One-tailed paired t-test. Scale bar in (G, H): 100μm.",
    "ncbi_link": "HSD17B7: 51478"
  },
  {
    "caption": "(D) Colony forming assays of the indicated SCC cell lines plus/minus HSD17B7 silencing as in the previous panels. Cells plated in triplicate dishes 5 days after lentiviral vector infection and selection were tested for clonogenic capability as in (A). Data are represented as number of colonies +/- SD. n(dishes per condition)= 3 *p<0.05, **p<0.01; p****<0.0001, 2-tailed unpaired t-test.",
    "ncbi_link": "HSD17B7: 51478"
  },
  {
    "caption": "(C, D) SCC13 cells stably infected with an HSD17B7-expressing lentivirus (HSD-oe) versus empty vector control (Ctrl) (C) or two HSD17B7-silencing lentivirus (shHSD2, shHSD4) versus vector control (shCtrl) (D) were analyzed as in the previous panels. Shown are individual values for 3 parallel cultures per condition together with mean +/- SD. **p<0.005; ***p<0.0005; ****p<0.0001. 2-tailed unpaired t-test. Additional metabolic measurement experiments of SCC cells plus/minus HSD17B7 overexpression and silencing, in the context of additional manipulations are shown in Fig 9.",
    "ncbi_link": "HSD2: 3291
HSD17B7: 51478
HSD: 51478
HSD4: 51444"
  },
  {
    "caption": "(C) Purified mitochondrial preparation from SCC13 cells infected with lentiviruses expressing wild type (HSD-wt) and Y193G and K197G mutated (HSD-mut) forms versus empty vector control (Ctrl) as in (B) were assayed for levels of Electron Transport Chain activity, ATP and mtROS production as in Fig 8A. Data are displayed as average values of triplicate measurements together with mean +/- SD. n(dishes per condition)= 3. **p<0.005; ***p<0.0005. 2-tailed unpaired t-test. Individual experimental values are provided in Dataset EV3.",
    "ncbi_link": "HSD: 51478"
  },
  {
    "caption": "(D) SCC13 cells were infected with two HSD17B7 silencing lentiviruses (shHSD2, shHSD4) versus vector control (shCtrl) followed, 3 days after infection and antibiotic selection, by treatment with Zymosterol (2.5uM) or ethanol vehicle alone for 48hours. Purified mitochondrial preparation were assayed for levels of Electron Transport Chain activity, ATP and mtROS production as in Fig 8A. Data are displayed as average values of triplicate measurements together with mean +/- SD. n(dishes per condition)= 3. ****p<0.0001, 2-tailed unpaired t-test. Individual experimental values are provided in Dataset EV3.",
    "ncbi_link": "HSD2: 3291
HSD17B7: 51478
HSD4: 51444"
  },
  {
    "caption": "Forebrain slices from WT (A-F) and S1928A KI mice (G-L) were treated with vehicle (water) or 10 M isoproterenol (ISO) for 0.5 - 10 min before solubilization, ultracentrifugation, IP of α11.2 (A-C, G-I) or β2AR (D-F, J-L), and sequential IB for pS1928, pS1700, and α11.2, for GluA1, or for β2AR, of corresponding regions of the blots, as indicated. All the α11.2 IPs in A-C and G-I were from the same samples (which were split in half for parallel IP) as the β2AR IPs in D-F and J-L, respectively (for quantification of coIP of β2AR with α11.2 see Figure EV1F,G).(A-F) In WT, the time-dependent increase in S1928 and S1700 phosphorylation (A-C) paralleled the decrease in coIP of β2AR with α11.2 (A bottom, Figure EV1F) and of α11.2 with β2AR (D-F).(G-L) In S1928A KI mice, ISO induced S1700 phosphorylation (G,I) but did not disrupt the α11.2 - β2AR interaction (G bottom, J-L, Figure EV1G).(B,C,H,I) For quantification of α11.2 phosphorylation, pS1928 and pS1700 signals were normalized to α11.2 (**p<0.01, ***p<0.001, ANOVA).",
    "ncbi_link": "α11.2: 12288"
  },
  {
    "caption": "Forebrain slices from WT (A-F) and S1928A KI mice (G-L) were treated with vehicle (water) or 10 M isoproterenol (ISO) for 0.5 - 10 min before solubilization, ultracentrifugation, IP of α11.2 (A-C, G-I) or β2AR (D-F, J-L), and sequential IB for pS1928, pS1700, and α11.2, for GluA1, or for β2AR, of corresponding regions of the blots, as indicated. All the α11.2 IPs in A-C and G-I were from the same samples (which were split in half for parallel IP) as the β2AR IPs in D-F and J-L, respectively (for quantification of coIP of β2AR with α11.2 see Figure EV1F,G).(A-F) In WT, the time-dependent increase in S1928 and S1700 phosphorylation (A-C) paralleled the decrease in coIP of β2AR with α11.2 (A bottom, Figure EV1F) and of α11.2 with β2AR (D-F).(G-L) In S1928A KI mice, ISO induced S1700 phosphorylation (G,I) but did not disrupt the α11.2 - β2AR interaction (G bottom, J-L, Figure EV1G).(B,C,H,I) For quantification of α11.2 phosphorylation, pS1928 and pS1700 signals were normalized to α11.2 (**p<0.01, ***p<0.001, ANOVA).(E,F,K,L) For quantification of coIP, α11.2 and GluA1 signals were normalized to β2AR (***p<0.001, One Way ANOVA).",
    "ncbi_link": "α11.2: 12288"
  },
  {
    "caption": "Graphs depict fEPSP initial slopes recorded from hippocampal CA1 before and after either a 5Hz/3 min (A-C) or 100Hz/1sec tetanus (D-F). Arrowheads mark onset of tetani and bars perfusion with 1 µM ISO. Inserts show sample traces immediately before (left) and ~30 min after (right) tetani.(A-C) Litter-matched WT but not conditional Cav1.2 KO mice showed PTT-LTP (**p < 0.001, one-way ANOVA).(D-F) WT as well as Cav1.2 KO mice showed NMDAR-dependent 100 Hz LTP.",
    "ncbi_link": "Cav1.2: 12288"
  },
  {
    "caption": "(A, B) Poly(I:C) treatment inhibits axonal growth at 3 DIV (A) and dendritic growth at 6 DIV (B) in WT neurons. Neurons were transfected with GFP at 1 or 4 DIV. One day later, neurons were treated with poly(I:C) for 24 h before harvest. (C) Axon and dendrite morphology of Tlr3-/- neurons after poly(I:C) treatment. Data in A,B,C were analyzed by unpaired t-test. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. ** P < 0.001, *** P < 0.0001. Scale bar, 20μm in A and B.",
    "ncbi_link": "Tlr3: 142980"
  },
  {
    "caption": "(D, E) Neuronal morphology in saline- and poly(I:C)-treated Tlr3+/+;Thy1-Yfp (D) and Tlr3-/-;Thy1-Yfp (E) mouse brains. Total dendrite length, dendritic tip number and Sholl analysis of dendritic processes were used to examine the dendrite phenotype. Data of dendrite length and tip number were analyzed by unpaired t-test. The Sholl data were analyzed by two-way ANOVA with Bonferroni's multiple comparison test. The numbers of analyzed neurons and mice are presented in each column. Mean values SEM are shown. * P < 0.05, ** P < 0.001, *** P < 0.0001. Scale bar, 50 μm in D and E.",
    "ncbi_link": "Thy1: 21838
Tlr3: 142980"
  },
  {
    "caption": "(A, B) Quantitation of dendrite morphology of Trif mutant neurons (A) and Myd88-/- neurons (B) after poly(I:C) stimulation. Trif mutant or Myd88-/- neurons were transfected with a GFP construct at 4 DIV and treated with poly(I:C) one day later. Neuron morphology was analyzed at 6 DIV according to the GFP signal. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by unpaired t-test.",
    "ncbi_link": "Myd88: 17874
Trif: 106759"
  },
  {
    "caption": "(C) MYD88 but not TRIF expression reduces dendrite outgrowth. HA-tagged MYD88 and TRIF were co-transfected with a GFP construct into cultured wild-type (WT) neurons at 4 DIV, and cell morphology was analyzed at 6 DIV. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by one-way ANOVA with Bonferroni's multiple comparison test.",
    "ncbi_link": "MYD88: 17874
TRIF: 106759"
  },
  {
    "caption": "(D) MYD88 knockdown, but not TRIF knockdown, robustly increases dendritic arbors and loses the response to poly(I:C). Three DIV neurons were transfected with control shRNA (shCtrl), MYD88 shRNA (shMYD88) or TRIF shRNA (shTRIF) and poly(I:C) was applied into the culture at 5 DIV for 24 h before harvest. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by two-way ANOVA with Bonferroni's multiple comparison test. Scale bar, 20 μm. *** P < 0.0001.",
    "ncbi_link": "MYD88: 17874
TRIF: 106759"
  },
  {
    "caption": "(C) Upper, schematic of MYD88 constructs. DD, death domain; ID, intermediate domain, TIR, TIR domain. Lower, coimmunoprecipitation of TLR3 and the N-terminal region of MYD88.",
    "ncbi_link": "MYD88: 17874"
  },
  {
    "caption": "(D) Full-length and N-terminal MYD88 inhibit dendrite outgrowth. Myd88-/- neurons were transfected with control vector (Ctrl), HA-tagged MYD88 (MYD88), N-terminal MYD88 (MYD88-N), or C-terminal MYD88 (MYD88-C) with a GFP construct. Poly(I:C) was applied into the culture at 5 DIV and neuronal morphology was analyzed at 6 DIV. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by two-way ANOVA with Bonferroni's multiple comparison test. Scale bar, 20 μm.",
    "ncbi_link": "MYD88: 17874
Myd88: 17874"
  },
  {
    "caption": "(E) Expression patterns of full-length and truncated fragments of MYD88 in Myd88-/- neurons. Representative images are shown.",
    "ncbi_link": "Myd88: 17874"
  },
  {
    "caption": "(A) qPCR analysis of proinflammatory cytokines Il-6, Tnfα, Il-1β and antiviral cytokine Ifnβ in WT cultured cortical and hippocampal neurons. Data were analyzed by unpaired t-test. Il-6 and Tnfα N=8; Ifnβ and Il-1β, N=6.",
    "ncbi_link": "Ifnβ: 15977
Il-1β: 16176
Il-6: 16193
Tnfα: 21926"
  },
  {
    "caption": "(B, C) Poly(I:C) treatment inhibits dendrite outgrowth of Il-6-/- neurons (B) and Tnfα-/- neurons (C). Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by unpaired t-test.",
    "ncbi_link": "Il-6: 16193
Tnfα: 21926"
  },
  {
    "caption": "(D) Left, schematic of experiment using conditioned medium. Upper right, conditioned medium applied to WT neurons. Lower right, conditioned medium applied to Tlr3-/- neurons. Dendrite morphology was analyzed one day after adding conditioned medium. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by unpaired t-test. * P < 0.05, *** P < 0.0001.",
    "ncbi_link": "Tlr3: 142980"
  },
  {
    "caption": "(B) Expression of 9 neuropsychiatric disorder-related genes in poly(I:C)-treated Tlr3-/- neurons. Relative expression levels compared with vehicle control are shown. In (B-D), dashed lines indicate the level of saline control.",
    "ncbi_link": "Tlr3: 142980"
  },
  {
    "caption": "(C, D) Expression of Auts2, Disc1, Fmr1, Pten and Ube3a in poly(I:C)-treated Myd88-/- neurons (C) and poly(I:C)-treated P5 WT mouse brains (D). In (B-D), dashed lines indicate the level of saline control.",
    "ncbi_link": "Auts2: 319974
Disc1: 244667
Fmr1: 14265
Myd88: 17874
Pten: 19211
Ube3a: 22215"
  },
  {
    "caption": "(A) Overexpression of WT DISC1, but not the DISC1 L604F mutant, in cultured neurons suppresses dendrite withdrawal induced by TLR3 activation. Mean values SEM of representatives of three independent experiments are shown. The numbers of analyzed neurons in the representative experiments are indicated in each column. Data were analyzed by two-way ANOVA with Bonferroni's multiple comparison test. Scale bar, 20 μm. * P < 0.05, ** P < 0.001, *** P < 0.0001.",
    "ncbi_link": "DISC1: 244667"
  },
  {
    "caption": "(B-C) Overexpression of DISC1 in cortical neurons of mouse brain is resistant to poly(I:C)-triggered reduction of dendritic arborization. Vector control (Ctrl) (B) or Myc-DISC1 (C) was co-expressed with GFP in cortical layer 2/3 neurons in mouse brain. After poly(I:C) injection at P4 and P5, the neuronal morphology was analyzed at P7 by tracing the GFP signals. The data of dendrite length and tip number were analyzed by unpaired t-test. The Sholl data were analyzed by two-way ANOVA with Bonferroni's multiple comparison test. The numbers of analyzed neurons collected from 3-4 mice of each group are indicated. Mean values SEM are shown. Scale bar, 30 μm. * P < 0.05, *** P < 0.0001.",
    "ncbi_link": "DISC1: 244667"
  },
  {
    "caption": "(C, D) Spine morphology of P21 Thy1-Yfp (C) and Tlr3-/-; Thy1-Yfp mice (D) after poly(I:C) stimulation at P4 and P5. One secondary dendrite of an apical dendrite of each somatosensory layer 5 cortical neuron was selected to examine the spine morphology. Three mice were analyzed for each group. Saline-treated Thy1-Yfp, 44 neurons; poly(I:C)-treated Thy1-Yfp, 43 neurons; saline-treated Tlr3-/-;Thy1-Yfp, 46 neurons; poly(I:C)-treated Tlr3-/-;Thy1-Yfp, 50 neurons. Mean values SEM are shown. Data were analyzed by unpaired t-test. Scale bar, 5 μm. *** P < 0.0001.",
    "ncbi_link": "Thy1: 21838
Tlr3: 142980"
  },
  {
    "caption": " A Representative traces (left), summary graphs of normalized frequency (middle) and normalized amplitude (right) of mIPSCs recorded from cultured cortical neurons that were infected with lentivirus expressing Munc18-1 WT or mutants, with or without Munc18-1 shRNAs (Control, n = 25; None, n = 17; WT, n = 17; QKAA, n = 18; KKEE, n = 16; P335A, n = 23; L348R, n = 21). B Sample traces (left), summary graphs of normalized amplitude (middle) and normalized charge transfer (right) of evoked IPSCs recorded from neurons as described in panel A (Control, n = 19; None, n = 19; WT, n = 19; QKAA, n = 13; KKEE, n = 18; P335A, n = 17; L348R, n = 21). C Sample traces (left) and quantification of the normalized charge transfer evoked by hypertonic sucrose (right) recorded from the neurons described in panel A (Control, n = 17; None, n = 13; WT, n = 17; QKAA, n = 17; KKEE, n = 18; P335A, n = 15; L348R, n = 14). ",
    "ncbi_link": "Munc18-1: 25558
Munc18-1: 20910"
  },
  {
    "caption": " A Representative images of HEK293T cells transfected with mCherry2-Syx1 or EGFP-Munc18-1. Lipophilic dye DiD (1,1-Dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine) was used as the plasma membrane marker. B Representative images of HEK293T cells co-transfected with mCherry2-Syx1 and EGFP labeled WT or mutants of Munc18-1. ",
    "ncbi_link": "EGFP: 
mCherry2: 
Syx1: 116470
Munc18-1: 25558"
  },
  {
    "caption": " C,D Summary graphs of the membrane distribution of Syx1 (C) and Munc18-1 WT or mutants (D) quantified by the ratio of fluorescence at the plasma membrane (PM) to the total fluorescence in the whole cell (total). DiD is the PM marker. Numbers of pictures analyzed are shown as follows: no Syx1, n = 14; no M18, n = 15; WT, n = 24; QKAA, n = 23; KKEE, n = 12; L348R, n = 22. ",
    "ncbi_link": "Syx1: 116470
Munc18-1: 25558"
  },
  {
    "caption": "CRTH2 subcellular localization in GFP-fused CRTH2 expressing plasmid-transfected cells. Red arrows indicate CRTH2 localized in the ER and white arrows indicate CRTH2 localized in the plasma membrane. Green, GFP-CRTH2; blue, DAPI; red, Calnexin; Scale bar, 20 μm.",
    "ncbi_link": "GFP: 
CRTH2: 14764"
  },
  {
    "caption": "Western blot analysis of CRTH2 expression in cell membrane and ER in NIH 3T3 and HEK293T cells. Myc-tagged CRTH2 expressing plasmid was transfected into NIH 3T3 and HEK293T cells. Whole cell lysate, plasma, and ER fractions were obtained 48 h after transfection. Calnexin and ATP1B were used as markers for ER and cell membrane, respectively.",
    "ncbi_link": "Myc: 
CRTH2: 14764"
  },
  {
    "caption": "Co-immunoprecipitation analysis of association of CRTH2 with LARP6. HEK293T cells were co-transfected with Myc-CRTH2 and Flag-LARP6 expressing plasmids. Whole cell lysates from HEK293T cells were immunoprecipitated and then immunoblotted with the indicated antibodies.",
    "ncbi_link": "Flag: 
Myc: 
LARP6: 67557
CRTH2: 14764"
  },
  {
    "caption": "Co-IP analysis of association of CRTH2 with GPR78. HEK293T cells were co-transfected with Myc-GPR78 expressing plasmids.",
    "ncbi_link": "Myc: 
GPR78: 14828"
  },
  {
    "caption": "Effect of LARP6 knockdown on Col1a1, Col1a2 and Col3a1 mRNA stability in WT and CRTH2-/- fibroblasts. *P < 0.05 vs WT, (two-way ANOVA); n = 8 for all groups.",
    "ncbi_link": "Col1a1: 12842
Col1a2: 12843
Col3a1: 12825
LARP6: 67557
CRTH2: 14764"
  },
  {
    "caption": "Effect of LARP6 knockdown on Collagen I and III protein expression in WT and CRTH2-/- fibroblasts.",
    "ncbi_link": "LARP6: 67557
CRTH2: 14764"
  },
  {
    "caption": ", Representative images of Masson′s trichrome staining of lung sections from CRTH2flox/floxCol1a2-CreERT (F-CRTH2 KO) and CRTH2flox/flox (Control) mice 14 days after bleomycin challenge. Blue indicates the collagen deposition regions. Scale bar, 100 μm. Quantification of collagen content in mouse lung sections after bleomycin challenge. *P < 0.05 vs control, #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 4 each; bleomycin groups, n = 8 each.",
    "ncbi_link": "Col1a2: 12843
Cre: 2777477
CRTH2: 14764"
  },
  {
    "caption": "Representative images of Masson′s trichrome staining of liver sections from control and F-CRTH2 KO mice 4 weeks after CCl4 challenge; Scale bar, 100 μm.",
    "ncbi_link": "CRTH2: 14764"
  },
  {
    "caption": "Representative images of Masson's trichrome staining of lung sections from F-LARP6 KO and F-LARP6/F-CRTH2 double KO (F-DKO) mice 14 days after bleomycin challenge; Scale bar, 100 μm. , Quantification of collagen content in mouse lung sections after bleomycin challenge. #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 4 each, bleomycin groups, n = 7-8. Hydroxyproline content in lungs from F-LARP6 KO and F-DKO mice treated with bleomycin. #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 4 each, bleomycin groups, n = 8 each.",
    "ncbi_link": "LARP6: 67557"
  },
  {
    "caption": "Representative images of Masson's trichrome staining of liver sections from F-LARP6 KO and F-DKO mice 4 weeks after CCl4 challenge; Scale bar, 100 μm. Quantification of collagen content in mouse liver sections after CCl4 challenge. #P < 0.05 vs mineral oil group (two-way ANOVA); mineral oil groups, n = 4 each, CCl4 groups, n = 8 each. Hydroxyproline content in livers from F-LARP6 KO and F-DKO mice treated with CCl4. #P < 0.05 vs mineral oil group (two-way ANOVA); saline groups, n = 4 each, CCl4 groups, n = 8 each.",
    "ncbi_link": "LARP6: 67557"
  },
  {
    "caption": "Representative images of Masson's trichrome staining of heart sections from F-LARP6 KO and F-DKO mice 21 days after ISO challenge; Scale bar, 50 μm. Quantification of collagen content in mouse heart sections after ISO challenge. #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 3 each, ISO groups, n = 7 each. , Hydroxyproline content in hearts from F-LARP6 KO and F-DKO mice treated with ISO. #P < 0.05 vs saline group (two-way ANOVA); saline groups, n = 4 each, ISO groups, n = 8 each.",
    "ncbi_link": "LARP6: 67557"
  },
  {
    "caption": "Quantification of collagen content in lung sections from Bumetanide-treated control (CRTH2flox/flox) and F-CRTH2 KO mice. *P < 0.05 vs control, #P < 0.05 vs Vehicle (two-way ANOVA); n = 7 for all groups. Effect of Bumetanide treatment on pulmonary hydroxyproline levels in control and F-CRTH2 KO mice. *P < 0.05 vs control; #P < 0.05 vs Vehicle (two-way ANOVA); n = 7 for all groups.",
    "ncbi_link": "CRTH2: 14764"
  },
  {
    "caption": "Bumetanide interferes with the interaction of CRTH2 with LARP6 in MRC-5 human lung fibroblasts MRC-5. MRC-5 cells were co-transfected with myc-LARP6 and flag-CRTH2 expressing plasmids for 24 h, and then treated with Bumetanide (0.1, 2 μM) for an additional 24 h. Whole cell lysates from MRC-5 cells were immunoprecipitated and immunoblotted with the indicated antibodies.",
    "ncbi_link": "flag: 
myc: 
LARP6: 67557
CRTH2: 14764"
  },
  {
    "caption": "LGG-1::GFP-positive puncta labeling autophagic membranes [22] were counted in wild-type or in food-limited animals.(A) Micrographs of eat-2(ad1116) L3 larvae expressing GFP-tagged lgg-1/LC3. Arrow indicates autophagic focus. Magnification is indicated.(B) Average number of LGG-1::GFP-containing puncta in eat-2(ad1116) mutants and N2 wild-type animals (WT), p < 0.0001.(C) Average number of LGG-1::GFP-containing puncta in N2 wild-type, food-restricted animals grown in liquid media (WT, food limited) and N2 wild-type animals grown in liquid with a higher concentration of bacteria (WT, fully fed), p < 0.0001; see Methods.Between three and ten seam cells were counted in each of 20-40 animals using high-power microscopy and averaged. n, total number of seam cells observed. Error bars: ±SEM. p-Values were calculated as unpaired, two-tailed t-test. Animals were raised at 20 °C. Please see Table S1 for quantification of all data.",
    "ncbi_link": "eat-2: 175072"
  },
  {
    "caption": "(A) Survival curves of eat-2(ad1116) animals fed either control bacteria or bacteria expressing bec-1 dsRNA during adulthood at 20 °C. Mean lifespan was 23.7 d for control and 19.6 d for bec-1 RNAi, p < 0.0001, Log-rank (Mantel-Cox) test. This experiment was performed a total of six times, and bec-1 RNAi shortened the lifespan of eat-2 animals ∼15%-30%. Please see Table 1 for additional data.(B) Survival curves of N2 wild-type animals (WT) fed either control bacteria or bacteria expressing bec-1 dsRNA during adulthood at 20 °C. These assays were performed concurrently with the eat-2 mutant lifespan analysis in Figure 2A. Mean lifespan was 17.3 d for control and 18.9 d for bec-1 RNAi. p = 0.045, Log-rank (Mantel-Cox) test. Depletion of bec-1 did not significantly change the lifespan of N2 or sterile fer-15(b26); fem-1(hc17) animals in any of six experiments. Please see Table 1 for additional data.(C) Survival curves of eat-2(ad1116) animals fed either control bacteria or bacteria expressing vps-34 dsRNA during adulthood at 20 °C. Mean lifespan was 27.6 d for control and 22.8 d for vps-34 RNAi, p = 0.0003, Log-rank (Mantel-Cox) test. This experiment was performed a total of four times. Please see Table 1 for additional data.(D) Survival curves of sterile fer-15(b26); fem-1(hc17) animals (WT) fed either control bacteria or bacteria expressing vps-34 dsRNA during adulthood at 20 °C. These assays were performed at the same time as the eat-2 lifespan analysis shown in Figure 2C. Mean lifespan was 21.5 d for control and 23.3 d for bec-1 RNAi. p = 0.14, Log-rank (Mantel-Cox) test. Depletion of vps-34 did not significantly change the lifespan of N2 or sterile fer-15(b26); fem-1(hc17) animals in each of six different experiments. Please see Table 1 for additional data.",
    "ncbi_link": "fer-15: 
bec-1: 177345
eat-2: 175072
fem-1: 177335
vps-34: 172280"
  },
  {
    "caption": "(A) Average number of LGG-1::GFP-containing puncta in eat-2(ad1116) progeny of animals fed either control bacteria or bacteria expressing bec-1, vps-34 or pha-4 dsRNA their entire lives. p ≤ 0.0001 for bec-1, vps-34 and pha-4 RNAi treatments compared to control, respectively, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details.",
    "ncbi_link": "bec-1: 177345
eat-2: 175072
pha-4: 180357
vps-34: 172280"
  },
  {
    "caption": "(B) Average number of LGG-1::GFP-containing puncta in rab-10(ok1494) progeny of animals fed either control bacteria or bacteria expressing pha-4 dsRNA their entire lives; p < 0.0001, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. Please see Figure 1 for details and Table S1 for quantification of data. Feeding mutants for several generations with pha-4 dsRNA, inhibited development and sharply decreased the number of eggs laid ([46], data not shown). However, the loss of many embryos was unlikely to bias our findings, since many progeny of daf-2 mutants treated with pha-4 RNAi also died but those that did not exhibited a robust autophagy phenotype (Figure 6).",
    "ncbi_link": "pha-4: 180357
rab-10: 266836"
  },
  {
    "caption": "(A) Average number of LGG-1::GFP-containing puncta in let-363/TOR RNAi-arrested animals compared to N2 wild-type animals (WT) grown on control (vector-only) bacteria, p < 0.0001, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details. We were not able to detect increased LGG-1::GFP puncta in long-lived let-363(RNAi) adults; however, one generation of daf-2 RNAi, our positive control, did not significantly increase the number of foci in adults either (data not shown). Please see Table S1 for quantification of all data.(B) Average number of LGG-1::GFP-containing puncta in daf-15(m81)/unc-24(e138) heterozygotes (daf-15/+) compared to N2 wild-type animals (WT), p < 0.0001, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details. Please see Table S1 for quantification of all data. daf-15 encodes the TOR-binding partner Raptor.",
    "ncbi_link": "daf-15: 177770
let-363: 172167
unc-24: 177594"
  },
  {
    "caption": "(C) Survival curves of daf-15(m81)/unc-24(e138) heterozygotes (daf-15/+, strain DR412) fed either control bacteria or bacteria expressing bec-1 dsRNA during adulthood at 20 °C. Mean lifespan: daf-15/+ animals grown on control RNAi-bacteria: 25.1 d, daf-15/+animals on bec-1 RNAi: 20.8 d, p = 0.0008, Log-rank (Mantel-Cox) test. The lifespan of daf-15/+ animals grown on bec-1 RNAi-bacteria during adulthood was measured again, yielding similar results; the lifespan of daf-15/+ animals was also measured three times following whole-life RNAi exposure. In these experiments, bec-1 RNAi generally shortened the mean lifespan of daf-15/+ animals to a greater extent than it shortened the lifespan of wild type. (We also attempted to perform double-RNAi experiments, in which animals were cultured on a 50:50 mixture of let-363/TOR and bec-1 [or control] RNAi bacteria. Although the trends we saw were in the expected direction, the effects produced by half-strength RNAi were small and not statistically significant [data not shown].) Please see Table 2 for additional data.(D) Survival curves of wild-type animals derived from strain DR412 (WT) fed either control bacteria or bacteria expressing bec-1 dsRNA throughout their whole life at 20 °C. These assays were performed concurrently with the daf-15/+ lifespan analysis shown in Figure 4C. WT grown on control RNAi-bacteria: 21.4 d, WT on bec-1 RNAi-bacteria: 21.1 d (p = 0.34), p between daf-15/+ and WT grown on control RNAi-bacteria, p < 0.0001, Log-rank (Mantel-Cox) test. Please see Table 2 for additional data.",
    "ncbi_link": "bec-1: 177345
daf-15: 177770
unc-24: 177594"
  },
  {
    "caption": "(A) Average number of LGG-1::GFP-containing puncta in N2 wild-type animals (WT) fed either control bacteria or bacteria expressing daf-2 (as a control) or rab-10 dsRNA for two generations. p < 0.0001 for either daf-2 or rab-10 RNAi treatment compared to control RNAi treatment, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details. Please see Table S1 for quantification of all data.(B) Average number of LGG-1::GFP-containing puncta in rab-10(ok1494) mutants compared to N2 wild-type animals (WT), p < 0.0001, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. Please see Figure 1 for details. Please see Table S1 for quantification of all data.",
    "ncbi_link": "daf-2: 175410
rab-10: 266836"
  },
  {
    "caption": "(C) Survival curves of rab-10(ok1494) animals fed either control bacteria or bacteria expressing bec-1 or vps-34 dsRNA during adulthood at 20 °C. Mean lifespan was 27.9 d for control, 19.9 d for bec-1 RNAi, and 22.1 d for vps-34 RNAi, all pair-wise comparisons to control, p < 0.0001, Log-rank (Mantel-Cox) test. This experiment was performed two times. Please see Table 3 for additional data.(D) Survival curves of N2 wild-type animals (WT) fed either control bacteria or bacteria expressing bec-1 or vps-34 dsRNA during adulthood at 20 °C. These assays were performed at the same time as the rab-10 lifespan analysis shown in Figure 5C. Mean lifespan was 22.9 d for control, 23.6 d for bec-1 RNAi, and 24.5 d for vps-34 RNAi, pair-wise comparison to control, p = 0.057 and p = 0.16, respectively, Log-rank (Mantel-Cox) test. Please see Table 1 for additional data.",
    "ncbi_link": "bec-1: 177345
rab-10: 266836
vps-34: 172280"
  },
  {
    "caption": "(A) Average number of LGG-1::GFP-containing puncta in daf-2(e1370) progeny of animals fed either control bacteria or bacteria expressing bec-1, vps-34, or pha-4 dsRNA for their entire lives. p < 0.0001 for bec-1 and vps-34 RNAi-bacteria compared to control RNAi-bacteria, respectively, p = 0.17 for pha-4 RNAi-bacteria compared to control RNAi-bacteria, unpaired, two-tailed t-test. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details. Feeding daf-2 mutants for several generations with pha-4 dsRNA sharply decreased the number of eggs laid (data not shown). The mean lifespan of daf-2(e1370) animals was shortened 12.5% by pha-4 RNAi ([28] and data not shown), and we measured an 11% decrease in puncta in daf-2(e1370) animals fed pha-4 RNAi. Even though this decrease was not statistically significant it remains possible that it relates to the small difference seen in lifespan.",
    "ncbi_link": "bec-1: 177345
daf-2: 175410
pha-4: 180357
vps-34: 172280"
  },
  {
    "caption": "(B) Average number of LGG-1::GFP-containing puncta in daf-16(mu86); daf-2(e1370) double mutants compared to daf-2(e1370) animals; p = 0.50, unpaired, two-tailed t-test. N2 wild-type animals (WT) are shown for comparison. n, total number of seam cells observed. Error bars: ±SEM. See Figure 1 for details. The double mutant expressing the LGG-1 reporter had a mean lifespan similar to non-transgenic daf-16; daf-2 double mutants (data not shown, [65]). Please see Table S1 for quantification of all data.",
    "ncbi_link": "daf-16: 172981
daf-2: 175410"
  },
  {
    "caption": "(F) AsiSI expression in U2OS cells was induced by OHT and cells were stained for RASSF1A and γH2AX. Boxed areas are shown in higher magnification. Nucleolar boundaries are marked with dashed lines. (G) Quantification of the number of cells with RASSF1A foci in (F). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "AsiSI: "
  },
  {
    "caption": "(H) U2OS cells with stable integration of a Lac operator (LacO) sequence adjacent to an I-SceI endonuclease site were transfected with Lac Repressor (LacR)-mCherry and GFP or GFP-NLS-HA-I-SceI. 24 h post transfection cells were fixed and stained for 53BP1 or RASSF1A. (I) Quantification of the LacO arrays enriched for 53BP1 or RASSF1A in (H). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "GFP: 
HA: 
I-SceI endonuclease: 
Lac operator: 
Lac Repressor: 
LacO: 
mCherry: "
  },
  {
    "caption": "(J) HeLa cells were transfected with I-PpoI endonuclease and stained for RASSF1A and γH2AX. Fluorescence intensity profiles of RASSF1A (green) and γH2AX (red) signals across the HeLa nuclei are shown. Position of line scan indicated by the yellow line.",
    "ncbi_link": "I-PpoI endonuclease: "
  },
  {
    "caption": "(A) HeLa cells were transfected with I-PpoI mRNA and collected at the indicated time points. Cells were co-stained for RASSF1A (R1A) and NBS1. Boxed areas are shown in higher magnification. Nucleolar boundaries are marked with dashed lines. (B) Quantification of (A). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(D) HeLa cells were transfected with the I-PpoI mRNA and 6 h later stained for RASSF1A-pS131 (R1A-pS131) and γH2AX. Fluorescence intensity profile of RASSF1A-pS131 (green) and γH2AX (red) signals across the HeLa nuclei are shown. Position of line scan indicated by the yellow line.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(E) Quantification of cells with RASSF1A-pS131 positive nucleolar caps 6 h post I-PpoI transfection. Error bars represent standard deviation and derive from 3 independent experiments. Representative images are shown in Fig EV3A.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(F) HeLa cells were treated with the ATMi or ATRi prior to transfection with I-PpoI mRNA. 6 h post mRNA transfection cells were stained for RASSF1A-pS131 (R1A-pS131). (G) Quantification of (F). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(H) HeLa cells were treated or not with ATM inhibitor (ATMi) followed by I-PpoI mRNA transfection and 6 h later cell lysates were analyzed by western blot for the indicated antibodies.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(I) HeLa cells were treated or not with ATMi followed by I-PpoI mRNA transfection and 6 h later cells were fixed and RASSF1A recruitment at rDNA DSBs was assessed. (J) Quantification of (I). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(A) HeLa cells with I-PpoI induced rDNA breaks were stained with the indicated antibodies. Intra-nucleolar cap localization for RASSF1A and 53BP1 in correlation with other proteins was accessed. Boxed areas are shown in higher magnification.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(B) HeLa cells were transfected with I-PpoI mRNA and stained for RASSF1A and 53BP1. Fluorescence intensity profiles of RASSF1A (green) and 53BP1 (red) signals across the HeLa nuclei are shown. Position of line scan indicated by the yellow line.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(C) HeLa cells were treated with siRNAs against LUCIFERASE (siLUC) or 53BP1 (si53BP1), 48 h later transfected with I-PpoI mRNA, fixed and stained for RASSF1A (R1A) and γH2AX. (D) Quantification of (C) and western blot analysis from siLUCIFERASE (siLUC) or si53BP1 treated cells for the indicated antibodies. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
53BP1: 7158"
  },
  {
    "caption": "(E) HeLa cells were treated with siRNAs against LUSIFERASE (siLUC) or RNF8 (siRNF8), 48 h later transfected for I-PpoI mRNA, fixed and stained for RASSF1A and γH2AX. (F) Quantification of (E) and western blot analysis from siLUCIFERASE (siLUC) or siRNF8 treated cells for the indicated antibodies. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
LUSIFERASE: 
RNF8: 9025"
  },
  {
    "caption": "(G) HeLa cells were treated with siRNA against 53BP1, or an ATM inhibitor (ATMi) followed by 5 Gy of ionizing radiation (γIR). Cells were fixed 2 h post treatment and stained for RASSF1A. Nucleolar boundaries are marked with dashed lines. (H) Quantification of cells with RASSF1A foci in (G). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "53BP1: 7158"
  },
  {
    "caption": "(K) U2OS cells were transfected with FLAG-RASSF1A (FLAG-R1A), FLAG-RASSF1A131A (FLAG-R1A131A) or pcDNA3 and 24 h later transfected with the I-PpoI mRNA. Cell lysates were subjected to immunoprecipitation against FLAG. Western blot analysis of total cell extracts and the IPs is shown.",
    "ncbi_link": "FLAG: 
I-PpoI: 
R1A: 11186
RASSF1A: 11186"
  },
  {
    "caption": "(A) U2OS cells were transfected with either HA-53BP1WT (aa1-1972), HA-53BP1ΔBRCT (aa 1-1709), HA-53BP1ΔΝterminus (aa 921-1972) or empty pcDNA3 vector and 24 h later transfected with I-PpoI mRNA. Cell lysates were subjected to immunoprecipitation with an HA tag antibody. Western blot analysis of total cell extracts and the IPs is shown.",
    "ncbi_link": "HA: 
I-PpoI: 
53BP1: 7158"
  },
  {
    "caption": "(B) U2OS cells were transfected with either full length MYC-RASSF1A or with the indicated RASSF1A deletion mutants and 24 h later transfected with I-PpoI mRNA. Cell lysates were subjected to immunoprecipitation with a MYC-tag antibody. Western blot analysis of the total cell extracts and the IPs is shown.",
    "ncbi_link": "I-PpoI: 
MYC: 
RASSF1A: 11186"
  },
  {
    "caption": "(C) HeLa cells were treated with siLUCIFERASE (siLUC) or si53BP1 and 48 h later transfected with I-PpoI mRNA and stained for ATM-pS1981. (D) Quantification of (C). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
53BP1: 7158"
  },
  {
    "caption": "(E-H) HeLa cells were treated with siLUCIFERASE (siLUC) or two different siRNAs against RASSF1A (siR1A_1 and siR1A_2) and 48 h later cells were transfected with I-PpoI mRNA to induce rDNA DSBs. 6 h post mRNA transfection, cells were stained for V5 to identify I-PpoI transfected cells and the other indicated antibodies. Representative images (E, F) and quantification of staining (G, H) for the indicated antibodies are shown. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
RASSF1A: 11186"
  },
  {
    "caption": "(I) HeLa cells were treated with siLUCIFERASE (siLUC), siRASSF1A or si53BP1 and 48 h later transfected with the I-PpoI mRNA. Cells were fixed and underwent ImmunoFISH against UBF and an rDNA probe. Boxed areas are shown in higher magnification. Nucleolar boundaries are marked with dashed lines. (J) HeLa cells were treated with siLUCIFERASE (siLUC), siRASSF1A or si53BP1 and 48 h later transfected with the I-PpoI mRNA. Cells were fixed and underwent ImmunoFISH against ATM-pS1981 and an rDNA probe. Boxed areas are shown in higher magnification. Nucleolar boundaries are marked with dashed lines.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
RASSF1A: 11186
53BP1: 7158"
  },
  {
    "caption": "(K) HeLa cells were treated with siLUCIFERASE (siLUC) or siRASSF1A followed by I-PpoI mRNA transfection. 6 h later cells were stained for 53BP1. (L) Quantification of (K). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
RASSF1A: 11186"
  },
  {
    "caption": "(M) U2OS cells were transfected with MYC-RASSF1A (1-340) or a RASSF1A mutant that lacks the SARAH domain, MYC-RASSF1A (1-288). Cells were transfected with I-PpoI mRNA and stained with the indicated antibodies.",
    "ncbi_link": "I-PpoI: 
MYC: 
RASSF1A: 11186"
  },
  {
    "caption": "(N) U2OS cells were transfected with MYC-RASSF1A (1-340) or MYC-RASSF1A (1-288). 24 h later cells were transfected with I-PpoI mRNA and harvested after 6 h. Cell lysates underwent cell fractionation and the chromatin bound fraction was analyzed by western blot.",
    "ncbi_link": "I-PpoI: 
MYC: 
RASSF1A: 11186"
  },
  {
    "caption": "(O) U2OS cells were treated with siRNA against RASSF1A followed by transfection with MYC-tag, MYC-RASSF1A (1-340) or MYC-RASSF1A (1-288). 24 h later cells were transfected with I-PpoI mRNA and stained for MYC expression and ATM-pS1981.",
    "ncbi_link": "I-PpoI: 
MYC: 
RASSF1A: 11186"
  },
  {
    "caption": "(A) HeLa cells were pre-treated with the ATMi or ATRi prior to transfection with I-PpoI mRNA. Cells were stained for RPA and quantified. Error bars represent standard deviation and derive from 3 independent experiments. (B) HeLa cells were pre-treated with the ATMi or ATRi prior to transfection with I-PpoI mRNA. Cells were stained for RAD51 and quantified. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: "
  },
  {
    "caption": "(C-F) HeLa cells were treated with siLUCIFERASE (siLUC) or two different siRNAs against RASSF1A (siR1A_1 and siR1A_2) and 48 h later cells were transfected with I-PpoI mRNA to induce rDNA DSBs. 6 h post mRNA transfection, cells were stained for V5 to identify I-PpoI transfected cells and the other indicated antibodies. Representative images (C, E) and quantification of staining (D, F) for the indicated antibodies are shown. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
R1A: 11186
RASSF1A: 11186"
  },
  {
    "caption": "(H) Cells were treated with siLUCIFERASE (siLUC) or si53BP1 and 48 h later transfected with I-PpoI mRNA and stained for RPA. (I) Quantification of (H). 107 values were analysed in siLUC and 90 values were analysed in si53BP1.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
53BP1: 7158"
  },
  {
    "caption": "(J) U2OS cells were treated with siLUCIFERASE (siLUC), siRASSF1A (siR1A) or si53BP1, treated with 10 μM BrdU for 24 h prior to I-PpoI mRNA transfection. 6 h post I-PpoI treated cells were pre-extracted, fixed and stained for BrdU under non denaturing conditions to visualize ssDNA. (K) Quantification of (J). Fold change of nuclear BrdU signal relative to siLUC is shown. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
R1A: 11186
RASSF1A: 11186
53BP1: 7158"
  },
  {
    "caption": "(L) HeLa cells were transfected with I-PpoI endonuclease and stained for MST2 and γH2AX. Fluorescence intensity profiles of MST2 (green) and γH2AX (red) signals across the HeLa nuclei are shown. Position of line scan indicated by the yellow line.",
    "ncbi_link": "I-PpoI endonuclease: "
  },
  {
    "caption": "(M) Validation of the MST2 siRNA with western blot.",
    "ncbi_link": "MST2: 6788"
  },
  {
    "caption": "(N) HeLa cells treated with siLUCIFERASE (siLUC) or siMST2 and 48 h later transfected with I-PpoI mRNA. Cells were treated with 5-EU for 30 min prior to fixation and assessed for incorporation. (O) Quantification of 5-EU intensity in siLUCIFERASE (siLUC) or siMST2 treated cells transfected with I-PpoI mRNA. Middle line represents the median and the boxes 25th and 75th percentiles. The whiskers mark the smallest and largest values. 100 values were analyzed in each condition.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
MST2: 6788"
  },
  {
    "caption": "(P) HeLa cells were treated with siLUCIFERASE (siLUC) or siMST2 and 48 h post transfection cells were transfected with I-PpoI mRNA. 6 h post transfection cells were fixed and stained for RASSF1A (R1A) and γH2AX. (Q) Quantification of (P). Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
MST2: 6788"
  },
  {
    "caption": "(R-W) HeLa cells treated with siLUCIFERASE (siLUC) or siMST2 and 48 h later transfected with I-PpoI mRNA. Cells were stained for ATM-pS1981 (R), KAP1-pS824 (T) and RPA (V) and quantified (S, U, W). 108 values in (S), 95 values in (U) and 100 values in (W) were analysed.",
    "ncbi_link": "I-PpoI: 
LUC: 
LUCIFERASE: 
MST2: 6788"
  },
  {
    "caption": "(C) Clonogenic survival analysis and representative images of HeLa cells treated with the indicated siRNAs followed by I‐PpoI WT or I-PpoI H98A mRNA transfections. Survival ratio I-PpoI WT/I-PpoI H98A in each siRNA condition is presented. Error bars represent standard deviation and derive from 3 independent experiments.",
    "ncbi_link": "I-PpoI: 
I‐PpoI: "
  },
  {
    "caption": "(E) 45S rDNA copy number analysis in patients' tumors compared to adjacent controls in the LUAD cohort. 67 tumor samples and 43 samples from adjacent tissue were analyzed. (F) 45S rDNA copy number analysis in the LUAD patient samples based on RASSF1A CpG promoter methylation. 67 samples were analysed.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "E The qRT-PCR validation of APA switching. Eight genes with lengthened and shortened 3' UTRs in HEK293T  and in MCF-7  cells were chosen. PRPF4B, CTNNBIP1, PHB  and RCL1  were selected from HEK293T cells, and rest genes are MCF-7 cells. KD (Extended/Common)/Ctr (Extended/Common) <1 indicates a shorter 3' UTR in the knockdown sample, and vice versa. Data are presented as mean ± SEM of three biological replicates. *p<0.05, **p<0.01, the p values were obtained from unpaired two-tailed Student's t-test.",
    "ncbi_link": "CTNNBIP1: 56998
PHB: 5245
PRPF4B: 8899
RCL1: 10171"
  },
  {
    "caption": "A Higher proportion of target genes in the list of genes with shortened 3'UTRs after knockdown of YTHDC1. The p values were obtained by Fisher's exact test. *p=1.227×10-3, **p=3.725×10-4, NA: no significance.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "E Scatter plot of protein and mRNA ratios of  dual luciferase report assay with λN-BoxB system. λN, YTHDC1  and λN-YTHDC1  were co-transfected with a bicistronic vector. Two batches of experiments with three biological repeats were performed. Both luciferase activity  and mRNA levels were measured. To test the effect of YTHDC1 binding  on the proximal APA site, a linear model with the co-transfected genes and batch as independent variables was fitted. Data are presented as mean ± SEM of three biological replicates. ** p<0.01 with t-test from linear model.",
    "ncbi_link": "λN: 2703540
YTHDC1: 91746"
  },
  {
    "caption": "F Overexpression of YTHDC1-WT and YTHDC1-Mut (W377A, W428A) revealed by Western blot.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "G Scatter plot of  qRT-PCR for APA validation. Mutation of the m6A binding  site of YTHDC1  loses its inhibitory effect on proximal APA sites. Extended/Common ratios of ten genes were obtained by qRT-PCR in HEK293T  cells overexpressing YTHDC1-WT and YTHDC1-Mut. The ratios were normalized to those of control cells. Data are presented as mean ± SEM of three biological replicates. *p<0.05, **p<0.01, ns: no significance. the p values were obtained from unpaired two-tailed Student's t-test.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "B Co-IP  assay using Myc-FIP1L1, Myc-PABPC1  and Myc-PABPC4  to pull down endogenous YTHDC1  in the presence of  RNase A.",
    "ncbi_link": "Myc: 
FIP1L1: 81608
PABPC1: 26986
PABPC4: 8761"
  },
  {
    "caption": "B Co-IP assays using truncated FIP1L1  proteins revealed that the proline-rich domain of FIP1L1  plays an important role in interacting  with YTHDC1.",
    "ncbi_link": "FIP1L1: 81608"
  },
  {
    "caption": "C Mutation of FIP1L1  nearly abrogates the interaction  between YTHDC1  and FIP1L1  compared with wild type.",
    "ncbi_link": "FIP1L1: 81608"
  },
  {
    "caption": "D-G Co-IP assays using different domains of YTHDC1  revealed that the N-terminus (1-344 aa) and YTH domain (364-507 aa) of YTHDC1 interact  with FIP1L1.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "B YTHDC1  inhibits the interaction  between Myc-FIP1L1  and FLAG-CPSF4. A substantially suppressed level of interaction  between Myc-FIP1L1  and FLAG-CPSF4  was observed when FLAG-YTHDC1  input was increased.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "C Knockdown of YTHDC1  enhances endogenous FIP1L1  recruitment to CPSF4, indicating that YTHDC1  plays an important role in interfering with the 3' end processing complex interaction.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "D YTHDC1   has little effect on the interaction  between Myc-FIP1L1  and FLAG-PAPOLA. The interaction  between Myc-FIP1L1  and FLAG-PAPOLA  was not significantly affected when FLAG-YTHDC1  was increased.",
    "ncbi_link": "FLAG: 
YTHDC1: 91746"
  },
  {
    "caption": "F The mutation of prolines in FIP1L1   abrogated the inhibitory effect of YTHDC1   on the interaction  between FIP1L1  and CPSF4.",
    "ncbi_link": "YTHDC1: 91746"
  },
  {
    "caption": "G qRT-PCR validation of APA site switching in a bicistronic dual luciferase system. FIP1L1-Mut could significantly increase the ratios of Rluc/Fluc  compared to FIP1L1-WT, indicating that YTHDC1  inhibits the use of proximal APA sites by interacting with the proline-rich domain of FIP1L1. Data are presented as mean ± SEM of three biological replicates. **p=8.77×10-4, the p values were obtained with unpaired two-tailed Student's t-test.",
    "ncbi_link": "Fluc: 
Rluc: 
FIP1L1: 81608"
  },
  {
    "caption": "E Sanger sequencing  was used to genotype eGFP-FIP1L1  and mScarlet-YTHDC1  homozygous cell lines.",
    "ncbi_link": "eGFP: 
mScarlet: 
FIP1L1: 81608
YTHDC1: 91746"
  },
  {
    "caption": "I Genome-edited eGFP-FIP1L1 HEK293T  cells expressing Dsred-YTHDC1-WT and Dsred-YTHDC1-Mut were examined by confocal microscopy. DsRed-YTHDC1-WT forms LLPS to compartmentalize FIL1L1, but DsRed-YTHDC1-Mut diffuses in the nucleus without droplet structure. Droplet structures are indicated by arrows. Scale bars: upper 8.09 µm, lower 6.64 µm. J Colocalization  of YTHDC1-WT and YTHDC1-Mut in figure I was assessed by calculating the average overlap coefficient according to Leica TCS SP8 microscope software. Data are presented as mean ± SEM of 15 cells. ****p=6.46×10-4, the p values were obtained with unpaired two-tailed Student's t-test.",
    "ncbi_link": "Dsred: 
DsRed: 
eGFP: 
FIP1L1: 81608
YTHDC1: 91746"
  },
  {
    "caption": "(A) Chromatin immunoprecipitation (ChIP) analysis of receptor binding to the ER8 element (region 1) of the nrf2 promoter. Immunoprecipitation with nonspecific IgG and PCR amplification of an adjacent region (2) served as controls. ChIP assays were also carried out to analyse binding to ER8s in the il10, ddit3 and tyrobp genes. RAR, retinoic acid receptor; VDR, vitamin D receptor.",
    "ncbi_link": "ddit3: 1649
il10: 3586
nrf2: 4780
tyrobp: 7305"
  },
  {
    "caption": "(B) Reverse transcription-PCR analysis of 1,25‐dihydroxyvitamin D3 (1,25D3)‐ or retinoic acid (RA)‐regulated expression of ddit3, il10, and tyrobp in U937, Calu‐3 and MCF‐7 cells.",
    "ncbi_link": "ddit3: 1649
il10: 3586
tyrobp: 7305"
  },
  {
    "caption": "(A) Electrophoretic mobility shift assay (EMSA) of binding of vitamin D receptors (VDRs)/retinoid X receptors (RXRs) to thep19ink4dER8, with binding to the mouseosteopontin (mop) DR3vitamin D responsive element as a control, along with a comparison of binding to ER6 and ER8 motifs (right‐hand panel).",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(B) EMSA of retinoic acid receptor (RAR)/RXR binding to the p19ink4d ER8, and the rarβ DR5 retinoic acid response element, as a control.",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(C) Chromatin immunoprecipitation (ChIP) analysis of binding of VDRs and RARs to the p19ink4d ER8 (region 1) and RNA polymerase II (POLII) binding to the transcription start site.",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(D) ReChIP analysis confirms the presence of VDR/RXRs and RAR/RXRs but not of VDR/RARs on the p19ink4d ER8.",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(E) Cloning of p19ink4d promoter containing or lacking ER8 upstream of a luciferase reporter. 3 (1,25D3)‐ (F) and retinoic acid (RA)‐regulated (G) luciferase expression is dependent on the ER8 element in the p19ink4d promoter. Luciferase expression driven by a thymidine kinase (tk) control promoter is shown.",
    "ncbi_link": "p19: 1032
thymidine kinase: 2703374"
  },
  {
    "caption": "3 and retinoic acid induce p19ink4d expression. Expression of p19ink4d messenger RNA by reverse transcription-PCR (A) or protein by western blotting (B) was carried out on extracts of cells treated with 3 (1,25D3) or retinoic acid (RA), as indicated.",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(C) Treatment with 1,25D3 or RA transiently enhances co‐immunoprecipitation (IP) of p19INK4D with cyclin‐dependent kinase CDK4 in U937 cells. Similar results were obtained in SCC25 cells (not shown). A control western blot (W) of CDK4 levels in ligand‐treated cells is shown below.",
    "ncbi_link": "p19: 1032"
  },
  {
    "caption": "(D) Treatment with 1,25D3 enhances co‐immunoprecipitation of p27KIP1 with CDK4 in U937 cells. Extracts of U937 cells were probed for p27KIP1 and CDK4, and immunoprecipitated with an anti‐CDK antibody and probed for p27KIP1 co‐immunoprecipitation.",
    "ncbi_link": "p27KIP1: 1027"
  },
  {
    "caption": "(A) Short interfering RNAs (siRNA) knockdown of p19ink4d messenger RNA and protein in SCC25 cells. SiRNAs were directed against p19ink4d, scrambled p19ink4d (Scr.) or cyclophilin (cyc.) controls.",
    "ncbi_link": "p19: 1032
cyclophilin: 835985"
  },
  {
    "caption": "(B) Combined knockdown of p27KIP1 and p19INK4D in SCC25 cells analysed by western blotting for p27KIP1 (top) and p19INK4D (bottom).",
    "ncbi_link": "p27KIP1: 1027
p19: 1032"
  },
  {
    "caption": "(C,D) Fluorescence‐activated cell sorting analysis of cell‐cycle distribution of control SCC25 cells, or cells transfected with scrambled (Scr), p19ink4d‐ or p27kip1‐directed siRNAs, individually or together (Dbl). (C) Cells were treated with vehicle or 1,25‐dihydroxyvitamin D3 (1,25D3), as indicated. (D) Cells were treated with DMSO vehicle, retinoic acid (RA) or 1,25D3, as indicated.",
    "ncbi_link": "p27kip1: 1027
p19: 1032"
  },
  {
    "caption": "(E) Loss of p19INK4D enhances lysosomal β‐galactosidase activity in SCC25 cells. (Left) Histogram of numbers of cells staining for β‐galactosidase activity in the absence (−) or presence of 1,25D3 in control cells (−) or in cells transfected with scrambled (Scr) or p19INK4D siRNAs. (Right) Bright field images of untransfected cells (−/−) or p19INK4D‐depleted cells treated with 1,25D3 (p19/D3).",
    "ncbi_link": "p19: 1032
p19INK4D: 1032"
  },
  {
    "caption": "(F) Loss of p19INK4D induces lysosomal fusion. Analysis of lysosomal fusion (autophagosomes) in SCC25 cells treated as in (E), stained for incorporation of lysotracker red. Nuclei were counterstained with Hoechst (blue).",
    "ncbi_link": "p19INK4D: 1032"
  },
  {
    "caption": "Media from soluble TREM2-Fc transfected HEK293T cells incubated with Aβ42 fibrils. Top left panel shows original media samples. Top right panel shows the presence of soluble TREM2 associated with Aβ42 pellet. The bottom two panels represent the same samples as the top, but probed with 6E10 RIPA lysate from TREM2 transfected HEK293T cells incubated with Aβ42 fibrils. Top left panel shows original RIPA lysate samples and top right panel shows the presence of TREM2 associated with Aβ42 pellet. The bottom two panels represent the same samples as the top, but probed with 6E10 Western blo had been cropped to facilitate the reading and originals with the supernatant fractions are available in Fig EV1. All experiments were replicated 3 independent times",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "Media from soluble TREM2-Fc and APOE3 co transfected HEK293T cells incubated with agarose beads anti-Human IgG Fc. Left panels show original media samples. Right panels show the purified soluble TREM2-Fc (bottom) and the presence of APOE3 with the purified soluble TREM2-Fc (top) Western blo had been cropped to facilitate the reading and originals with the supernatant fractions are available in Fig EV1. All experiments were replicated 3 independent times",
    "ncbi_link": "APOE3: 348
TREM2: 54209"
  },
  {
    "caption": "Media from soluble TREM-Fc family member transfected HEK293T cells incubated with Aβ42 fibrils. Top panel shows original media sample and the presence of TREM family members associated with Aβ42 pellet. Bottom panel shows original media and Aβ42 pellet probed with 6E10",
    "ncbi_link": "TREM: 54209"
  },
  {
    "caption": "Media from soluble TREM-Fc family members and APOE3 co transfected HEK293T cells incubated with agarose beads anti-Human IgG Fc. Top panel shows original media sample and the presence of soluble TREM family members associated with APOE3. Bottom panel shows original media and purified soluble TREM-Fc family members probed with anti-V5",
    "ncbi_link": "APOE3: 348
TREM: 54209"
  },
  {
    "caption": "2B4 NFAT-GFP reporter cells transduced with TREM2 or AD variant R47H were incubated with various concentrations of Aβ42 oligomers for 12 hours. GFP expression was detected at 1 µM Aβ42 oligomers with TREM2 transduced cells. No GFP expression was detected with Aβ42 oligomers from control transduced cells. Results were expressed as the percentage ± GFP cells averaged of ± standard error (n = 3, * p < 0.05 compared with mock, **** p< 0.0001 compared with mock, # p < 0.05 compared with TREM2, #### p < 0.0001 compared with TREM2, Two-way ANOVA, Bonferroni multiple comparisons, see Appendix table S3 for p value)",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": " B-2B4 NFAT-GFP reporter cells transduced with TREM2 or variants (R47H, R62H and T96K) were incubated with 10 µM Aβ42 oligomers for 12 hours. No GFP expression was detected with Aβ42 oligomers from control transduced cells. Results were expressed as the percentage GFP cells averaged of ± standard error (n = 3, * p < 0.05 compared with TREM2, ** p < 0.05 compared with TREM2, **** p< 0.0001 compared with TREM2, ## p < 0.01 compared with TREM2 T96K, #### p < 0.0001 compared with TREM2 T96K, ANOVA, Dunnett's multiple comparisons test, see Appendix table S3 for p value ",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "HEK293T cells transfected with TREM2 or AD variant incubated with 500 nM Aβ42 monomers were lysed for Aβ42 quantifications by ELISA. Expression of TREM2 increases Aβ42 level detected compared to mock control as well the AD variant. Results were averaged ± standard error (n = 9, # p < 0.05 compared with TREM2, ## p< 0.01 compared with TREM2, *** p< 0.001 compared with mock, **** p <0.0001 compared with mock, ANOVA, Tukey's Multiple Comparison Test, see Appendix table S3 for p value)",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "HEK293T cells transfected with TREM2 were incubated with Aβ42 oligomers for 16 hours. Conditioned media and cell lysate were analyzed by Western blot for TREM2 (RIPA lysate) and soluble TREM2 (media) detection. Experiment was replicated 3 independent times",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "HEK293T cells transfected with TREM2 were subjected to cell membrane biotinylation for purification. Bottom panel in D shows the presence of TREM2 in the purified product. Endogenous APP and β-tubulin were used as controls for the purification (middle and upper panels). Experiment was replicated 3 independent time",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": " D Real-time PCR analysis of Ido1 and Tgfb1 transcripts in pDCs stimulated for 18 h with TGF-β, in the presence or absence (Ctrl, control) of catalytic PI3K inhibitors, normalized to the expression of Gapdh and presented relative to results in untreated cells (dotted line, 1-fold). ",
    "ncbi_link": "Gapdh: 14433
Ido1: 15930
Tgfb1: 21803"
  },
  {
    "caption": "F Real-time PCR analysis of Ido1 and Tgfb1 transcripts in pDCs transfected with p110α-, β-, δ-specific, or negative control (nc) siRNA and stimulated for 18 h with TGF-β, normalized to the expression of Gapdh and presented relative to results in unstimulated cells (dotted line, 1-fold).",
    "ncbi_link": "Gapdh: 14433
Ido1: 15930
p110α: 18706
Tgfb1: 21803"
  },
  {
    "caption": "D Immunoblotting with anti-IDO1 and -p85 antibodies of IDO1 immunoprecipitates obtained from P1.HTR cells transfected with IDO1.WT or IDO1.Y149F. Mock-transfected P1.HTR cells were used as a control.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "A Confocal immunofluorescence microscopy images of P1.HTR cells either untransfected (Untr) or transfected with IDO1.WT (WT) or vector alone (Mock) and stained with antibodies recognizing IDO1 (green). Nuclei were stained with DAPI (blue). Scale bar, 20 µm.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "B Confocal immunofluorescence microscopy images of P1.HTR cells transfected with IDO1.WT, co-stained with antibodies recognizing IDO1 (green) and markers of intracellular organelles and structures (as indicated; red). Nuclei were stained with DAPI (blue). The merge imagine is shown for all stainings or without DAPI (no DAPI). Scale bar, 10 µm.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "C Immunoblotting analysis of EE purified from P1.IDO1.WT cells. Mock-transfected cells as in A were used as control.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "A Confocal immunofluorescence microscopy images of P1.HTR cells transfected with IDO1.WT or IDO1.Y149F and co-stained with antibodies recognizing IDO1 (green) and EEA1 (red). Nuclei were stained with DAPI (blue). The merge imagine is shown for all stainings or without DAPI (no DAPI). Scale bar, 10 µm.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "C Distribution of IDO1.WT and the IDO1.Y149F mutants in homogenates of P1.HTR cells along the isopycnic sucrose gradient as in Fig 3D. Fractions were immunoblotted using antibodies specific for IDO1.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "D The distribution of IDO1.WT and IDO1.Y149F proteins along the isopycnic sucrose gradient is shown in term of densitometric analysis in each fraction (mean ± SD of three experiments).",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "B Confocal immunofluorescence microscopy images of P1.HTR cells transfected with IDO1.WT incubated with class IA PI3K p110 isoform inhibitors (indicated) or medium alone (Ctrl) for 24 h and co-stained with antibodies recognizing IDO1 (green) and EEA1 (red). Nuclei were stained with DAPI (blue). The merge imagine is shown for all stainings or without DAPI (no DAPI). Scale bar, 10 µm.",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "D Tyrosine phosphatase activity in anti-IDO1 immunoprecipitates from P1.HTR cells transfected with IDO1.WT cells and treated with PI3K catalytic inhibitors (indicated) or medium alone (ctrl). Data represent the mean ± SD (n = 3 technical replicates).",
    "ncbi_link": "IDO1: 15930"
  },
  {
    "caption": "(C) Growth curves of strains deleted for car1, car2 or car3, and a wild-type control. Strains were grown in EMM (black), EMM with antimycin A (red), EMM with arginine (light blue) or EMM with both arginine and antimycin A (dark blue) as indicated.",
    "ncbi_link": "car3: 
car1: 2541313
car2: 2540626"
  },
  {
    "caption": "(D) Growth curves of strains deleted for car2 (top) or car3 (bottom). Strains were grown in EMM (black), EMM with antimycin A (red), EMM with arginine and antimycin A (dark blue), EMM with mix of all amino acids and antimycin A (bright blue), and EMM with antimycin A and each individual amino acid from the mix (grey).",
    "ncbi_link": "car3: 
car2: 2540626"
  },
  {
    "caption": "(E) Growth curves of wild-type control (WT) and car2 deletion strain (Δcar2). Strains were grown in EMM media with antimycin A and with either a mix of all amino acids (+AA mix) or different combinations of lysine (K), glutamine (Q), glutamic acid (E), or arginine (R) as indicated. Dashed line: time point where wild-type strain saturates in EMM with amino-acid mix.",
    "ncbi_link": "car2: 2540626"
  },
  {
    "caption": "(C) Heat map of expression changes for transcripts repressed over 2-fold at 30 min in cells supplemented with arginine (EMM +R) relative to cells without supplementation (EMM). Values for timepoints 0 and 30 min after antimycin A addition are shown for cells grown in EMM, EMM with arginine and ssp1 deletion mutant grown in EMM. The data are normalised to EMM timepoint 0.",
    "ncbi_link": "ssp1: 2538951"
  },
  {
    "caption": "G. Loss of LRP6 by serum starvation was mediated in a caveolin-1-dependent manner. HEK293 cells were transfected with caveolin siRNA and incubated in serum-free medium for 4 h. Cells were lysed and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "caveolin: 857
caveolin-1: 857"
  },
  {
    "caption": "B. Knockdown of LRP6 induced the phosphorylation of YAP even under nutrient-rich condition. HEK293T cells were transfected with GFP siRNA as a control and LRP6 siRNA under nutrient-rich conditions. The ratio of p-YAP/total-YAP of three independent immunoblot bands was quantified (biological replicates, right panel). Error bars indicate standard deviation of biological triplicate measurements. *P < 0.05. Student's t-test was used for statistical analysis.",
    "ncbi_link": "GFP: 
LRP6: 4040"
  },
  {
    "caption": "C. Overexpression of LRP6 blocked the increase of YAP phosphorylation under serum starvation conditions. HEK293T cells were transfected with empty vector (-) or LRP6-EGFP as indicated in the figure. One day after transfection, cells were incubated in serum-free medium for 4 h. Cells were lysed and the cell lysates were analyzed by immunoblotting (left panel). The ratio of LRP6/β-actin and p-YAP/YAP of three independent immunoblots was quantified (middle and right panel, respectively). Error bars indicate standard deviation of biological triplicate measurements. *P < 0.05 and ***P < 0.001. Student's t-test was used for statistical analysis.",
    "ncbi_link": "EGFP: 
LRP6: 4040"
  },
  {
    "caption": "D. Knockdown of LRP6 reduced YAP reporter activity. HEK293T cells were transfected with GFP siRNA as a control, LRP6 siRNA, pRL-TK and 8XGTIIC luciferase reporter constructs. One day after transfection, luciferase activity was measured. Error bars indicate standard deviation of biological triplicate measurements. ***P < 0.005. Student's t-test was used for statistical analysis.",
    "ncbi_link": "8XGTIIC: 
GFP: 
luciferase: 
TK: 
LRP6: 4040"
  },
  {
    "caption": "E. Knockdown of LRP6 reduced the expression of YAP target genes. Quantitative real-time PCR assay measuring the expression of CTGF, ANKRD1, INHBA, and LRP6 mRNA in GFP and LRP6 siRNA-transfected HEK293T cells was performed. Quantification of CTGF, ANKRD1, INHBA, and LRP6 mRNA was normalized against the level of β-actin. Error bars indicate standard deviation of technical triplicate measurements. *P < 0.05, **P < 0.01 and ***P < 0.001. Student's t-test was used for statistical analysis.",
    "ncbi_link": "GFP: 
β-actin: 
ANKRD1: 27063
CTGF: 1490
INHBA: 3624
LRP6: 4040
YAP: 10413"
  },
  {
    "caption": "F. Knockdown of LRP6 reduced the interaction between YAP and TEAD. HEK293T cells were transfected with EGFP-YAP, Myc-TEAD4 and siRNA for LRP6. Cells were lysed and the cell lysates were immunoprecipitated with anti-Myc antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
Myc: 
LRP6: 4040
TEAD4: 7004
YAP: 10413"
  },
  {
    "caption": "G. Overexpression of LRP6 rescued the reduced YAP reporter activity under serum starvation conditions. HEK293T cells were transfected with an empty vector (-) or VSVG-LRP6, and with pRL-TK and 8XGTIIC luciferase reporter constructs. One day after transfection, cells were incubated in serum-free medium for 4 h and luciferase activity was measured. Error bars indicate standard deviation of biological triplicate measurements. ***P < 0.001. Student's t-test was used for statistical analysis.",
    "ncbi_link": "8XGTIIC: 
luciferase: 
TK: 
VSVG: 
LRP6: 4040"
  },
  {
    "caption": "H. Knockdown of LRP6 induced cytoplasmic localization of YAP. HEK293A cells were transfected with siRNA for GFP or LRP6 and immunofluorescence analysis was performed. Figure shows representative image of multiple areas. DAPI was used for nucleus staining. Scale bars: 10 μm. Quantification of nuclear YAP is shown in the right panel. Quantification was performed by counting cells that have nuclear-localized YAP per image (n=8). Error bars indicate standard deviation. ***P < 0.001. Student's t-test was used for statistical analysis.",
    "ncbi_link": "GFP: 
LRP6: 4040"
  },
  {
    "caption": "I. Overexpression of LRP6 induced nuclear localization of YAP under starvation conditions. HEK293A cells were transfected with LRP6-EGFP and 1 d after transfected cells were incubated with or without serum-containing medium for 4 h, and immunofluorescence analysis was performed. Figure shows representative image of multiple areas. DAPI was used for nucleus staining. Scale bars: 10μm. Quantification of nuclear YAP is shown in the right panel. Quantification was performed by counting cells that have nuclear localized YAP per image (n=6). Error bars indicate standard deviation. *P < 0.05. Student's t-test was used for statistical analysis.",
    "ncbi_link": "EGFP: 
LRP6: 4040"
  },
  {
    "caption": "A. Knockdown of LRP6 activated LATS1. HEK293T cells were transfected with siRNA for GFP and LRP6. After transfection, cells were lysed and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
LRP6: 4040"
  },
  {
    "caption": "B. Overexpression of LRP6 reduced the amount of the active form of LATS1 that was induced by serum starvation. HEK293T cells were transfected with empty vector (-) or VSVG-LRP6. 1 d after transfection, cells were incubated in serum-free medium for 4 h. After incubation, cells were lysed, and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "VSVG: 
LRP6: 4040"
  },
  {
    "caption": "C. Merlin and LATS1/2 were necessary for the LRP6-knockdown-mediated YAP phosphorylation. HEK293T cells were transfected with siRNA for GFP, LRP6, Merlin, and LATS1/2. Cells were lysed and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
LATS1: 9113
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "D. Merlin and LATS1/2 were necessary for the LRP6-knockdown-mediated decrease of YAP reporter activity. HEK293T cells were seeded and transfected with siRNA for GFP, LRP6, Merlin and LATS1/2. After 1 d, these cells were transfected again with pRL-TK and 8XGTIIC luciferase reporter constructs. One day after transfection, cells were lysed and luciferase activity was measured. Error bars indicate standard deviation of biological triplicate measurements. **P< 0.01 and N.S: Non-significant. Student's t-test was used for statistical analysis.",
    "ncbi_link": "8XGTIIC: 
GFP: 
luciferase: 
TK: 
LATS1: 9113
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "E. Merlin and LATS1/2 were necessary for the LRP6 knockdown-mediated-cytoplasmic localization of YAP. HEK293A cells were transfected with siRNA for GFP, LRP6, Merlin, and LATS1/2, and immunofluorescence analysis was performed. The figure shows representative images of multiple areas. DAPI was used for nucleus staining. Scale bars: 10 μm. Quantification of cells that have nuclear YAP is shown in Fig EV3B.",
    "ncbi_link": "GFP: 
LATS1: 9113
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "F. YAP phosphorylation by loss of LRP6 was dependent on the interaction between Merlin and LATS1/2. HEK293T cells were transfected with siRNA for GFP, LRP6, and Merlin, and after 1 d were transfected again with HA-Merlin and HA-Merlin∆FERM. Cells were lysed and the cell lysates were analyzed by immunoblotting. The arrow indicates endogenous Merlin and HA-Merlin, and the arrowhead indicates HA-Merlin∆FERM.",
    "ncbi_link": "GFP: 
HA: 
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "G. MST1/2 were necessary for the LRP6-knockdown-mediated activation of LATS1/2. HEK293T cells were transfected with siRNA for GFP, LRP6 and MST1/2. Cells were lysed and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
LRP6: 4040
MST1: 4485"
  },
  {
    "caption": "H. MAP4K4/6/7 were necessary for the LRP6 knockdown mediated activation of LATS1/2. HEK293T cells were transfected with siRNA for GFP, LRP6, and MAP4K4/6/7. Cells were lysed and the cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
LRP6: 4040
MAP4K4: 9448"
  },
  {
    "caption": "A. The interaction between overexpressed Merlin and LRP6 was reduced under serum starvation condition. HEK293T cells were transfected with Flag-Merlin and LRP6-EGFP. After transfection, cells were incubated in serum-free medium for overnight with Bafilomycin A1 (20 nM). The cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting with the indicated antibodies. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
Flag: 
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "D. The interaction between overexpressed Merlin and LATS1 was increased under serum starvation. HEK293T cells were transfected with Myc-LATS1 and EGFP-Merlin. After transfection, cells were incubated in serum-free medium for overnight and then were lysed. The cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
Myc: 
LATS1: 9113
Merlin: 4771"
  },
  {
    "caption": "E. Knockdown of LRP6 enhanced the interaction between overexpressed Merlin and LATS1. HEK293T cells were transfected with Myc-LATS1, EGFP-Merlin and LRP6 siRNA. Cells were lysed and the cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
Myc: 
LATS1: 9113
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "F. Knockdown of LRP6 enhances the interaction between endogenous Merlin and LATS1. HEK293T cells were transfected with siRNA for GFP or LRP6. After transfection, cells were lysed and the cell lysates were immunoprecipitated with anti-Merlin antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "GFP: 
LRP6: 4040"
  },
  {
    "caption": "B. LRP6 is O-GlcNAcylated. LRP6-EGFP-transfected HEK293T cells were treated in Thiamet G (30 μM) or OSMI-1 (50 μM) for 6 h with Bafiolmycin A1 (100nM). After treatment, cells were lysed and the cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
LRP6: 4040"
  },
  {
    "caption": "E. The O-GlcNAcylation on LRP6 was reduced under serum starvation condition. HEK293T cells were transfected with LRP6-EGFP. Cells were incubated in serum-free medium with Bafilomycin A1 (100 nM) for 4 h. After incubation, cells were lysed and the cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting. WCL, whole-cell lysates. The ratio of O-GlcNAc/EGFP from three independent immunoblots was quantified (biological replicates, bottom panel). *P < 0.05. Error bars indicate standard deviation of biological triplicate measurements. Student's t-test was used for statistical analysis.",
    "ncbi_link": "EGFP: 
LRP6: 4040"
  },
  {
    "caption": "F. Increase of O-GlcNAcylation enhanced the interaction between ectopically expressed LRP6 and Merlin. LRP6-EGFP and Flag-Merlin transfected HEK293T cells were incubated in serum-free medium with Bafilomycin A1 (20 nM) and Thiamet G (30μM) overnight. Cells were lysed and the cell lysates were immunoprecipitated with anti-EGFP antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "EGFP: 
Flag: 
LRP6: 4040
Merlin: 4771"
  },
  {
    "caption": "G. Enhancement of global O-GlcNAcylation blocked the serum starvation-mediated increase of interaction between overexpressed LATS1 and Merlin. HEK293T cells were transfected with Myc-LATS1 and Flag-Merlin. After transfection, cells were incubated in serum-free medium with Thiamet G (30μM) and Bafilomycin A1 (20nM) overnight. Cells were lysed and the cell lysates were immunoprecipitated with anti-Myc antibody and analyzed by immunoblotting. WCL, whole-cell lysates.",
    "ncbi_link": "Flag: 
Myc: 
LATS1: 9113
Merlin: 4771"
  },
  {
    "caption": "qRT-PCR for INHBA relative to RPL27 using RNA from SCC13 cells transduced with a lentiviral vector allowing expression of INHBA in a doxycycline (DOX)-inducible manner (SCC13 Act clone 1 and 2) or empty vector (EV) (N=3). SCC13 Act and EV cell lines were generated from lentivirally transduced cells upon single cell clonal expansion.",
    "ncbi_link": "INHBA: 3624
Act: 3624
RPL27: 6155"
  },
  {
    "caption": "Western blot of cell lysate and conditioned media (CM; bottom) of transduced SCC13 cells for the activin βA subunit and GAPDH (loading control for cell lysate) under reducing conditions. The higher molecular weight of recombinant activin βA results from the HA-epitope tag. Ponceau S staining of the membrane was used as a loading control for the CM.",
    "ncbi_link": "activin βA: 3624"
  },
  {
    "caption": "Representative pictures of 5 week-old tumors (indicated by arrows) formed in NOD/SCID mice upon intradermal injection of SCC13 Act (clone 2) or SCC13 EV cells and tumor volume at different time points of tumor development. N=3-6 tumors.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images of H&E stainings of tumors formed by SCC13 EV and Act cells (clone 2) at day 35 (asterisk indicates cartilage, arrow indicates site of invasion). An inset panel indicates the area where tumor cells invade into the cartilage. Tumor sections were evaluated for invasion through the basement membrane. N=6 (EV), N=6 Act (3 tumors from clone 1 and 3 tumors from clone 2). Tumors from Act mice were pooled in the graph).",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images of sections from tumors formed by SCC13 EV and SCC13 Act (clone 2) stained for Ki67 (red), PDGFR-α (green) and counterstained with Hoechst (blue). Quantification of Ki67/PDGFR-α positive cells is shown in the graph. N=3 tumors, n=3-4 histological sections.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images of sections from 3D cultures of primary human skin fibroblasts with either SCC13 EV or SCC13 Act (clones 1 and 2) cells stained with either H&E or Herovici.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Quantification of Ki67-positive cells in sections from SCC13 EV and SCC13 Act (clone 2) organotypic cultures (co-stained with E-cadherin to indicate epithelial cells). N=3 independent cultures, n=3 histological sections.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images of sections from SCC13 EV and SCC13 Act (clone 2) organotypic cultures stained for K14 (red) and collagen IV (green) combined with Hoechst staining (blue) and quantification of the K14-positive area below the basement membrane (BM). N=3 independent cultures, n=4 histological sections. The area indicated with a white rectangle in the left picture is shown at higher magnification in the right picture.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "qRT-PCR and Western blot analyses of ACTA2/αSMA expression using total RNA/lysates of fibroblasts treated with activin A or TGF-β1 for 6 h. N=3. The membrane was re-probed with GAPDH and mDia2 antibodies.",
    "ncbi_link": "ACTA2: 11475"
  },
  {
    "caption": "qRT-PCR analysis of CAF marker genes relative to Rps29 using RNA from fibroblasts treated with activin A for 6 h. N=3.",
    "ncbi_link": "Rps29: 6235"
  },
  {
    "caption": "qRT-PCR for INHBA relative to RPL27 using RNA from primary human fibroblasts transduced with a lentiviral vector allowing expression of INHBA in an inducible manner after treatment with DOX for 24 h (Fb Act, clones 1 and 2) or with empty vector (Fb EV) (N=3). Fb Act and Fb EV cultures were generated from lentivirally-transduced cells upon clonal expansion of resistant single cells.",
    "ncbi_link": "INHBA: 3624
Act: 3624
RPL27: 6155"
  },
  {
    "caption": "Chemotactic migration of SCC13 cells for 24 h in a transwell assay containing CM from Fb Act (clone 2) or Fb EV. N=4. Migration in one control culture was set to 1.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Relative colony area of SCC13 cells upon culture in CM from Fb Act (clone 2) or EV. N=3.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative immunofluorescence images of de-cellularized matrix from Fb Act (clone 2) and Fb EV stained for fibronectin or collagen I.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Relative colony area of SCC13 cells plated on either de-cellularized matrix from Fb Act (clone 2) or Fb EV. N=3.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Migration of SCC13 cells plated on either de-cellularized matrix from Fb Act (clone 2) or Fb EV. N=6. The experimental setup is shown schematically above the graph.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Fb Act (clone 2) or Fb EV cells were cultured together in 2D with SCC13 cells. After 7 day of culture SCC13 cells were identified by K14 and the number of K14-positive colony area was quantified. N=6.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Quantification of SCC13 tumor spheroid area in single hanging drop including CM from Fb EV or Fb Act (clone 2) (including 1% FBS), DMEM/1% FBS, or DMEM/1% FBS plus 20 ng/mL recombinant activin A. The area of the spheroid formed in one Fb EV sample was set to 1. N=9-10 hanging drops.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images and quantification of K14-stained areas from 3D cultures of SCC13 cells seeded on top of either Fb Act (clone 2) or Fb EV. N=3 independent cultures, n=3 histological sections.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative pictures of tumors formed in NOD/SCID mice 6-7 weeks after intradermal injection of SCC13 cells with Fb Act (clone 2) or Fb EV. Tumor volume at different time points of tumor development (6-7 weeks after injection). N=5 tumors per group.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "mDia2 (Diap3) expression quantified by RNA sequencing of fibroblasts isolated from ear skin. N=3 pools of 3-6 mice.",
    "ncbi_link": "Diap3: 56419
mDia2: 56419"
  },
  {
    "caption": "Primary mouse fibroblasts were treated with activin A or TGF-β1 or vehicle for 6h and analyzed by qRT-PCR (N=3) and Western blot for mDia2 (Diap3) and mDia2 expression, respectively. The GAPDH loading control is identical to the one in Fig 2C, since the same membrane was probed for mDia2, αSMA and GAPDH.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "Immortalized mouse fibroblasts were transduced with a lentivirus expressing a DOX-inducible dominant-negative ActRIB mutant (dnActRIB) or an empty lentivirus (EV), treated with activin A for 2.5 h and analyzed by Western blot for mDia2 and GAPDH.",
    "ncbi_link": "ActRIB: 11479"
  },
  {
    "caption": "Representative sections of ear skin tumors formed by SCC13 EV or SCC13 Act cells (clone 2) stained for mDia2 or K14 (green) (top), mDia2 (green) or MECA32/LYVE1 (red, bottom) and counterstained with Hoechst (blue).",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "qRT-PCR for mDia2/DIAPH3 relative to RPL27 using RNA from normal human skin (N=11), SCCs (N=9) and BCCs (N=7).",
    "ncbi_link": "DIAPH3: 81624
mDia2: 81624
RPL27: 6155"
  },
  {
    "caption": "Expression levels of mDia2/DIAPH3 in tumor and normal tissues based on TCGA cancer data (TCGA data version 20141017, http://firebrowse.org/). Gene expression levels were presented as normalized log2 RSEM (RNA-Seq by Expectation-Maximization) index from the database. BLCA: Bladder Urothelial Carcinoma (N = 408 & 19 tumor and normal tissue samples, respectively), BRCA: Breast Invasive Carcinoma (N = 1100 & 112), CESC: Cervical SCC (N = 306 & 3), ESCA: Esophageal SCC (N = 185 & 11), HNSC: Head-Neck SCC (N = 522 & 44), LIHC: Liver Hepatocellular Carcinoma (N = 373 & 47), LUSC: Lung SCC (N = 501 & 51), PAAD: Pancreatic Adenocarcinoma (N = 179 & 4), PRAD: Prostate Adenocarcinoma (N = 496 & 50), READ: Rectum Adenocarcinoma (N = 167 & 10), STES: Stomach and Esophageal Carcinoma (N = 600 & 46), UCEC: Uterine Corpus Endometrial Carcinoma (N = 546 & 35). Box plot shows relative mDia2/DIAPH3 expression in human tumor (red) and normal (blue) tissue. Boxes indicate the interquartile range, whiskers indicate data points within 1.5 times interquartile range, dots outside the whiskers indicate outliers, and the central line indicates median.",
    "ncbi_link": "DIAPH3: 81624
mDia2: 81624"
  },
  {
    "caption": "Relative gene expression of mDia2/DIAPH3 and INHBA in the stroma of intrahepatic cholangiocarcinoma, breast and colorectal cancers vs. stroma of respective normal tissues based on datasets GSE45001 (D) (N = 10 normal tissue & 10 cancer samples, GSE9014 (E) (N = 4 & 13), and GSE35602 (F) (N = 6 & 53), and in CAFs from breast cancer samples vs. normal breast fibroblasts (GSE29270 dataset) (G) (N = 5 & 23). NS: Normal stroma, CS: Cancer stroma, NF: Normal fibroblasts, CAF: Cancer-associated fibroblasts). The expression values of the datasets were obtained using GEO2R tool in the GEO database.",
    "ncbi_link": "DIAPH3: 81624
mDia2: 81624
INHBA: 3624"
  },
  {
    "caption": "Immortalized mouse fibroblasts were transduced with a lentiviral vector expressing different mDia2-targeting shRNAs (shmDia2 #1-3) or empty vector (sh-EV). The knock-down was confirmed by qRT-PCR (N=3), Western blot and immunofluorescence.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "Ki67 staining of mDia2 knock-down and control mouse fibroblasts. N=3.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "migration in scratch assays of mDia2 knock-down and control mouse fibroblasts. N=3.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "qRT-PCR for mDia1, mDia3, Fmn1 and Fmn2 and several CAF genes relative to Rps29 using RNA from control (sh-EV) and mDia2 knock-down (sh-mDia2) fibroblasts. N=3.",
    "ncbi_link": "mDia1: 13367
mDia2: 56419
mDia3: 56419
Fmn1: 14260
Fmn2: 54418
Rps29: 20090"
  },
  {
    "caption": "Representative images of mDia2 knockdown and control mouse fibroblasts stained for p53 (left), and quantification of cells showing accumulation of p53 in the nucleus (right). N=3.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "Representative Western blots for p53, vinculin and histone H1 using nuclear and cytoplasmic fractions and total lysate of mDia2 knock-down (F) or activin A-treated fibroblasts (6h, 20 ng/ml) (G) and control mouse fibroblasts and quantification of the nuclear p53/histone H1 ratio. Vinculin and histone H1 were used as loading controls for the cytoplasmic and nuclear fractions, respectively. N=6.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "Representative Western blots for p53, mDia2 and GAPDH using total lysates of mDia2 knock-down and control mouse fibroblasts treated for 24 h with pifithrin-α (PFT-α) (15 μM).",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "Representative p53 immunofluorescence images of mDia2 knock-down mouse fibroblasts treated with PFT-α or vehicle (DMSO) (top) and quantification of cells showing accumulation of p53 in the nucleus (bottom). N=3.",
    "ncbi_link": "mDia2: 56419"
  },
  {
    "caption": "qRT-PCR for mDia2, Postn, Mmp13, Fn1, Spp1 and Acta2 relative to Rps29 using RNA from mDia2 knock-down and control fibroblasts treated with PFT-α or vehicle. N=3.",
    "ncbi_link": "Acta2: 11475
mDia2: 56419
Fn1: 14268
Mmp13: 17386
Postn: 50706
Rps29: 20090
Spp1: 20750"
  },
  {
    "caption": "Colony size of SCC13 Act cells (clone 2) after co-culture with either immortalized mDia2 knockdown (sh-mDia2) or control (sh-EV) mouse fibroblasts. N=4.",
    "ncbi_link": "mDia2: 56419
Act: 3624"
  },
  {
    "caption": "Representative pictures of 5-week-old tumors formed upon intradermal co-injection of SCC13 Act cells (clone 2) with sh-EV or sh-mDia2 knock-down immortalized mouse fibroblasts. Graph shows tumor volume at different timepoints of tumor development. N=3-5 tumors per group.",
    "ncbi_link": "mDia2: 56419
Act: 3624"
  },
  {
    "caption": "Representative immunofluorescence images of sections from ear skin tumors formed by SCC13 Act (clone 2) co-injected with sh-EV or sh-mDia2 fibroblasts, stained for E-cadherin (green) and periostin or p53 (red), counterstained with Hoechst (blue).",
    "ncbi_link": "mDia2: 56419
Act: 3624"
  },
  {
    "caption": "Tumor volume at different time points after co-injection of SCC13 cells with EV or dnActRIB fibroblasts. N=5 tumors.",
    "ncbi_link": "ActRIB: 11479"
  },
  {
    "caption": "Representative immunofluorescence images of sections from ear skin tumors formed by SCC13 cells co-injected with EV or dnActRIB fibroblasts stained for K14 (left) or PDGFRα (right) (green) and mDia2 (red), counterstained with Hoechst (blue). Bar graph shows the percentage of mDia2-positive area. N=3.",
    "ncbi_link": "ActRIB: 11479"
  },
  {
    "caption": "SCC13 EV or SCC13 Fst cells were injected into the ear skin of NOD/SCID mice and tumor weight was determined 12 weeks after injection. N=9-10 tumors.",
    "ncbi_link": "Fst: 14313"
  },
  {
    "caption": "Representative immunofluorescence images of sections from ear skin tumors formed by SCC13 EV or SSC13 Fst cells stained for K14 or mDia2 (red), counterstained with Hoechst (blue). Bar graph shows the percentage of mDia2-positive area. N=3.",
    "ncbi_link": "Fst: 14313"
  },
  {
    "caption": "Tumors formed by SCC13 Act cells were treated ex vivo for 6h with follistatin (FST) (50 ng/ml) and/or SMIFH2 (10 μM), or with activin A (20 ng/ml) and stained for Ki67. N=3 tumor explants, n=4 histological sections.",
    "ncbi_link": "Act: 3624"
  },
  {
    "caption": "Representative images of spheroids formed by SCC13 Act cells labeled with PKH67 (green) with primary human fibroblasts embedded in collagen gels and graph showing increase in the spheroid area between day 0 and day 3. Spheroids were either treated with FST (50 ng/ml) or SMIFH2 (10 μM) or left untreated. N=6-8 tumor spheroids.",
    "ncbi_link": "FST: 10468
Act: 3624"
  },
  {
    "caption": "Mutations in epg-7 cause defective degradation of SQST-1 aggregates. (A and B) In wild-type embryos, SQST-1::GFP is weakly expressed and diffusely localized in the cytoplasm. (A) DIC image of the embryo shown in B. (C) Elevated expression level and accumulation of many SQST-1::GFP aggregates in epg-7 mutant embryos.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(D) Compared with wild type and epg-2 mutants, levels of SQST-1 are dramatically elevated in atg-3 and epg-7 mutant embryos in an immunoblotting assay.",
    "ncbi_link": "atg-3: 176921
epg-2: 171787
epg-7: 180996"
  },
  {
    "caption": "(E-G) Compared with wild-type embryos (E and F), endogenous SQST-1 shows dramatically elevated levels and accumulates into a large number of aggregates in epg-7 mutant embryos (G). ∼200-cell stage embryos are shown in E-G. (E) DAPI image of the embryo shown in F.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(H) Number of SQST-1 aggregates per focal plane in wild type, atg-3 mutants, and epg-7 mutants.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(I-L) At the ∼100-cell stage, far fewer SQST-1 aggregates are formed in epg-7 mutants than in atg-3 mutants. (I and K) DAPI images of the embryos shown in J and L, respectively.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(N) Compared with wild-type animals, levels of ZK1053.4::GFP are dramatically elevated in atg-3 and epg-7 mutants.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(O-R) ZK1053.4::GFP is weakly expressed in wild-type embryos (O-P) and sqst-1 mutants (R), but forms a large number of aggregates in epg-7 mutants (Q). (O) DIC image of the embryo shown in P.",
    "ncbi_link": "epg-7: 180996
sqst-1: 178139"
  },
  {
    "caption": "(S) Survival curve of L1 larvae under food depletion conditions in wild type, epg-1 mutants, and epg-7 mutants. This experiment was completed once (wild type: n = 2,964; epg-7: n = 602; epg-1: n = 215). Statistical analysis of L1 survival shows that epg-7 mutants exhibit significant difference to wild type and also to epg-1 mutants (log-rank test, P = 0.000).",
    "ncbi_link": "epg-1: 176150
epg-7: 180996"
  },
  {
    "caption": "(T) Loss of function of epg-7 does not ameliorate the degeneration of mec-4::gfp-labeled touch neurons caused by mec-4(u231).",
    "ncbi_link": "epg-7: 180996
mec-4: 181728"
  },
  {
    "caption": "(U) Survival curves of wild type and various mutants. sqst-1;epg-7 mutants have a shortened mean and maximum life span. (P = 0.000 for epg-7 or wild type vs. sqst-1;epg-7 in all three repeats; log-rank test).",
    "ncbi_link": "epg-7: 180996
sqst-1: 178139"
  },
  {
    "caption": "(V) Survival of hydrogen peroxide-treated animals. (In all three repeats, P = 0.000 for epg-7 vs. sqst-1;epg-7; P > 0.2 for wild type vs. sqst-1;epg-7; log-rank test).",
    "ncbi_link": "epg-7: 180996
sqst-1: 178139"
  },
  {
    "caption": "(W) Survival of animals at the indicated time after heat shock treatment. (P < 0.05 for wild type vs. epg-7 or epg-7 vs. sqst-1;epg-7 at 5, 6, and 7 h).",
    "ncbi_link": "epg-7: 180996
sqst-1: 178139"
  },
  {
    "caption": "(X) Dauer formation of daf-2(e1370) mutants in different backgrounds.",
    "ncbi_link": "daf-2: 175410"
  },
  {
    "caption": "(D) A large number of SQST-1::GFP aggregates accumulate in epg-7 mutant embryos carrying an epg-7(del Atg11) transgene.",
    "ncbi_link": "Atg11: 
epg-7: 180996"
  },
  {
    "caption": "(E and F) No SQST-1 aggregates are detected in epg-7 mutants carrying an epg-7::gfp reporter. (E) DAPI image of the embryo shown in F.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(J) Compared with wild-type animals, levels of EPG-7::GFP are dramatically elevated in epg-4 mutants, but remain unchanged in sqst-1 mutants.",
    "ncbi_link": "epg-4: 176009
sqst-1: 178139"
  },
  {
    "caption": "(K) The expression level of EPG-7::GFP is dramatically elevated and many EPG-7::GFP aggregates are formed in lgg-1 mutant embryos.",
    "ncbi_link": "lgg-1: 174050"
  },
  {
    "caption": "(L and M) No EPG-7 aggregates, detected by anti-EPG-7 antibody, are formed in wild-type embryos. (L) DAPI image of the embryo shown in M. (N) Levels of EPG-7 are dramatically elevated and a large number of EPG-7 aggregates are formed in atg-3 mutants. (O) No EPG-7 aggregates are formed in sqst-1 mutant embryos.",
    "ncbi_link": "atg-3: 176921
sqst-1: 178139"
  },
  {
    "caption": "(A) EPG-7 colocalizes with SQST-1 aggregates in epg-8 mutant embryos. Colocalization was defined as two aggregates showing >70% overlap in their fluorescence signals. Insets show a magnified view.",
    "ncbi_link": "epg-8: 172847"
  },
  {
    "caption": "(H and I) SQST-1 aggregates accumulate in epg-7 mutant embryos carrying an epg-7(del 531-631)::gfp transgene. (H) DAPI image of the embryo shown in I.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(J and K) EPG-7(del 531-631)::GFP is weakly expressed and diffusely localized in epg-7(tm2508) embryos. Its expression is not elevated in lgg-1(RNAi) animals. H-K show embryos carrying the same transgene. Images in J and K were taken using the same exposure time.",
    "ncbi_link": "epg-7: 180996
lgg-1: 174050"
  },
  {
    "caption": "(N) Levels of SQST-1(del 26-181)::GFP are dramatically elevated in epg-7 and atg-3 mutants.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(O and P) SQST-1(del 26-181)::GFP is weakly expressed and diffusely localized in sqst-1(ok2892) mutant embryos. (O) DIC image of the embryo shown in P.",
    "ncbi_link": "sqst-1: 178139"
  },
  {
    "caption": "(Q and R) SQST-1(del 26-181)::GFP is expressed at dramatically elevated levels and accumulates into a large number of aggregates in lgg-1 (Q) and epg-7 (R) mutants.",
    "ncbi_link": "epg-7: 180996
lgg-1: 174050"
  },
  {
    "caption": "(E) Loss of function of epg-7 does not increase levels of LGG-1 and also does not suppress accumulation of LGG-1 in epg-3 mutant embryos.",
    "ncbi_link": "epg-3: 176712
epg-7: 180996"
  },
  {
    "caption": "(F-H) Expression of LGG-1 in epg-7 mutant embryos before the ∼100-cell stage (F), at the ∼200-cell stage (G), and at the fourfold stage (H). Images in B-D and F-H were taken using the same exposure time.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(I) SQST-1 aggregates are separable from LGG-1 puncta in epg-7 mutant embryos. Insets show a magnified view. (J) In epg-6 mutant embryos, LGG-1 puncta and SQST-1 aggregates are enlarged and colocalized. (K) LGG-1 and SQST-1 aggregates are smaller in size and largely separable in epg-6;epg-7 double mutants. (I-K) DAPI images of the embryos shown in the same row.",
    "ncbi_link": "epg-6: 189705
epg-7: 180996"
  },
  {
    "caption": "(L-O) Enlarged LGG-1 and SQST-1 aggregates are colocalized in epg-4 mutants (L and M). Simultaneously depleting epg-7 reduces the size of LGG-1 puncta and SQST-1 aggregates, which become largely separable (N and O). (L and N) DAPI images of the embryos shown in M and O, respectively.",
    "ncbi_link": "epg-4: 176009
epg-7: 180996"
  },
  {
    "caption": "(P) In atg-9 mutant embryos, LGG-1 puncta largely colocalize with SQST-1 aggregates at the comma stage. Notably, there are more SQST-1 aggregates than LGG-1 puncta. (Q) SQST-1 aggregates are separable from LGG-1 puncta in atg-9;epg-7 mutants at the comma stage.",
    "ncbi_link": "atg-9: 178561
epg-7: 180996"
  },
  {
    "caption": "(R) Percentage of LGG-1 puncta colocalized with SQST-1 aggregates in indicated autophagy mutants. Comma-stage embryos were examined for atg-9 and atg-9;epg-7 mutants. ∼200-cell stage embryos were examined for other autophagy mutants.",
    "ncbi_link": "atg-9: 178561
epg-7: 180996"
  },
  {
    "caption": "(I) SQST-1 associates with LGG-1 in vivo. Embryonic extracts from epg-7 mutants show that interaction of SQST-1 with LGG-1 is EPG-7 independent.",
    "ncbi_link": "epg-7: 180996"
  },
  {
    "caption": "(L and M) SQST-1(del LGG-1-1+2)::GFP, in which the two LGG-1-binding fragments (amino acids 418-499 and 604-630) are deleted, is weakly expressed and diffusely localized in the cytoplasm in sqst-1(ok2892) mutants. (N and O) Loss of function of lgg-1 dramatically elevates the expression level of SQST-1(del LGG-1-1+2)::GFP, which forms a large number of aggregates. (L and N) DIC images of the embryos shown in M and O, respectively",
    "ncbi_link": "lgg-1: 174050
sqst-1: 178139"
  },
  {
    "caption": "(P) SQST-1(del LGG-1-1+2)::GFP aggregates colocalize with EPG-7 in lgg-1;sqst-1 mutants. Insets show a magnified view.",
    "ncbi_link": "lgg-1: 174050
sqst-1: 178139"
  },
  {
    "caption": "Formation of ATG-9 puncta in various autophagy mutants. (A and B) In wild-type embryos, ATG-9::GFP is diffusely localized in the cytoplasm. (A) DIC image of the embryo shown in B. Insets show a magnified view. (C) ATG-9::GFP forms a large number of small, intense puncta in epg-1 mutants. (D and E) Accumulation of ATG-9::GFP puncta in unc-51(D) and epg-1 (E) mutants is independent of lgg-1. (F) The ATG-9::GFP puncta largely disappear in epg-1;epg-7 mutants. (G) ATG-9::GFP accumulates into large punctate structures in epg-6 mutants. (H) Loss of function of lgg-1 suppresses the accumulation of ATG-9::GFP puncta in epg-6 mutants. (I) Loss of function of epg-7 has no effect on the formation of ATG-9::GFP puncta in epg-6 mutants. The ATG-9::GFP puncta are smaller in epg-6;epg-7 mutants than those in epg-6 single mutants. (J-L) ATG-9::GFP accumulates into large punctate structures in epg-4 mutants (J) and the accumulation is suppressed by simultaneously depleting the activity of lgg-1 (K) or epg-7 (L). (M and N) In epg-8 mutants, ATG-9 accumulates into aggregates (M) that are suppressed by loss of lgg-1 activity (N). (O) epg-7 mutants exhibit the same distribution pattern of ATG-9::GFP as wild-type embryos. (P) Percentage of ATG-9::GFP puncta colocalized with EPG-7 and SQST-1 aggregates in indicated autophagy mutants.",
    "ncbi_link": "epg-1: 176150
epg-4: 176009
epg-6: 189705
epg-7: 180996
epg-8: 172847
lgg-1: 174050
unc-51: 180311"
  },
  {
    "caption": "(Q-T) The ATG-9::GFP puncta in epg-6 (Q), epg-8 (R), unc-51 (S), and atg-18 (T) mutants colocalize with EPG-7 aggregates.",
    "ncbi_link": "atg-18: 179246
epg-6: 189705
epg-8: 172847
unc-51: 180311"
  },
  {
    "caption": "(U and V) ATG-9::GFP puncta in epg-6 (U) and epg-8 (V) mutants colocalize with SQST-1 aggregates. (W and X) In unc-51 (W) and atg-18 (X) mutants, ATG-9::GFP partially colocalizes with SQST-1 aggregates.",
    "ncbi_link": "atg-18: 179246
epg-6: 189705
epg-8: 172847
unc-51: 180311"
  },
  {
    "caption": "(A2) Levels of W07G4.5::GFP in wild type, epg-7 mutants, and atg-3 L1 larvae before and after 6 h starvation treatment. (B2) Model for the role of epg-7 in degradation of SQST-1 aggregates. SQST-1 directly interacts with EPG-7 and is recruited into EPG-7 aggregates. EPG-7 also associates with multiple Atg proteins, which may be recruited to the SQST-1-EPG-7 complex in a hierarchical order. IM, isolation membrane. (C2) Hierarchical relationship of the scaffold proteins EPG-2 and EPG-7 and other essential ATG and EPG proteins in the aggrephagy pathway",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(A and B) C17E4.2::GFP is weakly expressed and diffusely localized in a wild-type embryo. (A) DIC image of the embryo shown in B. (C and D) C17E4.2::GFP is expressed at dramatically elevated levels and accumulates into many aggregates in lgg-1 (C) and epg-7 (D) mutant embryos.",
    "ncbi_link": "epg-7: 180996
lgg-1: 174050"
  },
  {
    "caption": "(E and F) W07G4.5::GFP is expressed in the intestine and a few aggregates are formed in a wild-type embryo at the fourfold stage. (E) DIC image of the embryo shown in F. (G and H) W07G4.5::GFP is expressed at dramatically elevated levels and accumulates into a large number of aggregates in atg-3 (G) and epg-7 (H) mutants.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(I) Levels of C33D9.6::GFP and W07G4.5::GFP are dramatically elevated in atg-3 and epg-7 mutant embryos.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996"
  },
  {
    "caption": "(J and K) C17E4.2 aggregates in atg-3 mutants overlap with EPG-7 aggregates (J), but are separable from SQST-1 aggregates (K). Insets show a magnified view. (L) Colocalization frequency of C17E4.2, C33D9.6, and W07G4.5 aggregates with EPG-7 and SQST-1 aggregates in atg-3 mutants.",
    "ncbi_link": "atg-3: 176921"
  },
  {
    "caption": "(M) SQST-1::GFP accumulates in hypodermal cells in epg-7 mutants at the larval stage. (N) SQST-1::GFP aggregates disappear in rheb-1(RNAi);epg-7 mutant larvae. (O) Dramatic accumulation of SQST-1::GFP aggregates in hypodermal cells in atg-3 mutant larvae. (P) SQST-1::GFP aggregates persist in rheb-1(RNAi);atg-3 mutant larvae.",
    "ncbi_link": "atg-3: 176921
epg-7: 180996
rheb-1: 176327"
  },
  {
    "caption": "(Q-T) At larval stages, W07G4.5::GFP forms aggregates in intestinal cells (Q and R). These aggregates disappear upon RNAi knockdown of let-363 (S and T). (U-X) W07G4.5::GFP aggregates accumulate in intestinal cells in epg-7 mutant larvae (U and V). These aggregates disappear when let-363 is simultaneously depleted (W and X). (Y and Z) In atg-3 mutants, W07G4.5::GFP aggregates accumulate in intestinal cells (Y) and persist after RNAi knockdown of let-363 (Z).",
    "ncbi_link": "atg-3: 176921
epg-7: 180996
let-363: 172167"
  },
  {
    "caption": "D) BDNF decreases mCherry-CLIMP63 co-localization with TRBP, but not with PACT or Ago2. Hippocampal neurons were transfected with GFP and mCherry-CLIMP63 at 7DIV and immunostained three days later, following BDNF or control stimulation. Manders co-localization was measured at the cell soma using GFP as a mask as indicated (p=0.01, t-test type 3, n=4, error bars; s.d.).",
    "ncbi_link": "CLIMP63: 362859"
  },
  {
    "caption": "B) Short BDNF stimulation changes the levels of only a few microRNAs, such as miR-16-5p and miR-551b-5p. Volcano plot of small RNA sequencing data from BDNF- or control-treated cortical neurons (6DIV) was based on differential expression analysis using the edgeR package. Individual points represent the average fold change obtained in three independent experiments for each miRNA, and plotted against obtained p-values. MiRNAs above the red dashed line are significant (p<0.05, t-test type 2, n=3).",
    "ncbi_link": "miR-16-5p: 100313997
miR-551b-5p: 100314268"
  },
  {
    "caption": "C) BDNF stimulation leads to a transient decrease in mature miR-16-5p levels. 6DIV cortical neurons were treated with BDNF for 10 or 20 minutes and mature miRNA levels were measured in rtPCR. Ct values for each miRNA were normalized to U6 and to 20 minutes of control stimulation (n=3, p=0.02, t-test type 3, error bars; s.d.).",
    "ncbi_link": "miRNA: 
U6: 
miR-16-5p: 100313997"
  },
  {
    "caption": "D) BDNF stimulation leads to a transient increase in the levels of pre-miR16 after 10 minutes of BDNF stimulation. Ct values obtained in rtPCR were normalized to U6 and to 20 minutes control stimulation (n=4, t-test type 3, error bars; s.d.).",
    "ncbi_link": "U6: 
miR16: 100313997"
  },
  {
    "caption": "E) BDNF causes a decrease in pre-miR16 binding to TRBP. Cortical neurons were treated with BDNF or vehicle control and RNA IPs were performed using a mouse monoclonal anti-TRBP antibody. Ct values measured in rtPCR were normalized to respective inputs (n=3, p=0.002, t-test type 3, error bars represent s.d.).",
    "ncbi_link": "miR16: 100313997"
  },
  {
    "caption": "A) BDNF changes the canonical isomiR proportion of a subset of miRNAs. IsomiR levels were compared to the total amount of the corresponding miRNA. Shown are the miRNAs that had significant changes in the canonical isomiR (annotated as '0', p<0.05, t-test type 2, n=3). Results are shown in order of decreasing significance. Shown in red are miRNAs of the miR16 family, miR-16-5p and miR-15b-5p. Black squares correspond non-existing isomiRs. Numbers on the top of the table represent the trimming (negative) or addition (positive) of nucleotides to the 3'- or 5'-end of the canonical 5p or 3p isomiRs, respectively. Only templated nucleotide additions and trimmings, which might reflect Dicer-mediated pre-miRNA cleavage, were considered for analysis.",
    "ncbi_link": "isomiR: 
isomiRs: 
miRNA: 
miRNAs: 
miR-15b-5p: 100314150
miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "B) BDNF stimulation leads to a decrease in the canonical (22 nucleotides) isomiRs of the miR16 family, miR-16-5p (p=0.005) and miR-15b-5p (p=0.02). In both cases, this is accompanied by an increase in the levels of shorter isomiRs; the 19-nucleotide isoform of miR-16-5p (p=0.04) and the 21-nucleotide isoform of miR-15b-5p (p=0.007). The relative isomiRs proportion was calculated as described in A (t-test type 2, n=3, error bars; s.d.).",
    "ncbi_link": "isomiRs: 
miR-15b-5p: 100314150
miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "B) Endogenous miR-16-5p activity in developing hippocampal neurons. Hippocampal neurons were transfected with 500ng miR16 or control sensor at 4 DIV and with or without LNA control ('LNA Ctrl') or the anti-sense miR-16-5p inhibitor ('LNA-miR16'). Cells were fixed at 7 DIV and the number of neurons expressing GFP and not dsRed ('GFP-only') was compared to the total number of transfected neurons. LNA-miR16 reduces the amount of repression of the miR16 sensor compared to LNA-Ctrl (n=4, p=0.02, t-test type 2, error bars represent s.d.).",
    "ncbi_link": "miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "C) Short-term BDNF stimulation inhibits endogenous miR-16-5p activity. Hippocampal neurons were transfected at 4 DIV and treated with BDNF either 24h or 20 minutes before fixation and neurons were counted as in B. Repression index was obtained by normalizing the miR16 sensor to the control sensor condition in each experiment (n=4, p=0.02, t-test type 3, error bars; s.d.).",
    "ncbi_link": "miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "D&E) Inhibition of miR-16-5p increases dendritic complexity and occludes BDNF-induced dendritogenesis. D) Hippocampal neurons were transfected with the control sensor (A), and stimulated with control or BDNF 24 hours before fixation. Pictures were obtained on a confocal microscope and thresholds were set to dsRed signal fluorescence in order to distinguish individual dendrites (scale bars are 10μm). E) To quantify dendritic complexity the total number of dendritic intersections was calculated using Sholl analysis. Values were normalized to LNA-Ctrl and control treatment (n=3, p<0.04, t-test type 3, error bars represent s.d.).",
    "ncbi_link": "miR-16-5p: 100313997"
  },
  {
    "caption": "F&G) Overexpression of miR-16-5p blocks BDNF-induced dendritogenesis. F) Hippocampal neurons were transfected with control sensor and either control miRNA mimic (miR-Ctrl) or a miR-16-5p mimic (miR16) and treated two days later with BDNF or control vehicle. DsRed signal fluorescence was used to set a threshold on images obtained on a confocal microscope (scale bars; 10μm). G) Total number of intersections was quantified in Sholl analysis and values were normalized to miR-Ctrl, control treatment in each experiment (n=4, p=0.02, t-test type 3, error bars; s.d.).",
    "ncbi_link": "miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "B) MiR-16-5p targets the 3'UTR of the BDNFmRNA. Cortical neurons were transfected with 100ng pmiRGlo dual-luciferase reporter consisting of the 3'UTR of BDNF (3'UTR WT) or a miR-16-5p-binding site mutant (3'UTR Mut) and either miR-Ctrl or miR-16. The Firefly to Renilla luciferase ratio was measured and values were normalized to the respective reporter expression without miRNA mimic co-transfection (n=3, p=0.02, t-test type 2).",
    "ncbi_link": "BDNF: 24225
miR-16: 100313997
MiR-16-5p: 100313997"
  },
  {
    "caption": "C) BDNFstimulation leads to an increase in the translation of 3'UTR WT (p=0.02, t-test type 3) but not 3'UTR Mut luciferase reporter, which is rescued by miR-16-5p overexpression (p=0.002; t-test type 2). Cortical neurons were transfected as in (B), stimulated with BDNF or vehicle control for 20 minutes, and lysed two hours after stimulation (n=4).",
    "ncbi_link": "miR-16-5p: 100313997"
  },
  {
    "caption": "D) Pre-miR16 is present in the neuronal cell soma and processes of hippocampal neurons. Neurons were plated on compartmentalized chambers and RNA was isolated from the neuronal cell body and processes separately. Pre-miR137 and pre-miR341 were used to assay somatic and neurite enrichment, respectively. Raw Ct values were normalized to GAPDH mRNA in each experiment (n=3).",
    "ncbi_link": "GAPDH: 24383
Pre-miR137: 100314031
Pre-miR16: 100313997
pre-miR341: 100313979"
  },
  {
    "caption": "More Dicer binds to membrane-targeted GFP-TRBP (mGFP-TRBP) compared to GFP-TRBP. HEK293T cells were transfected with GFP, GFP-TRBP or mGFP-TRBP and cell lysates were processed for co-IP using anti-GFP antibody. Dicer binding was normalized to respective input lanes in each condition (n=4, p=0.02; t-test type 2, error bars are s.d.).",
    "ncbi_link": "TRBP: "
  },
  {
    "caption": "B) mGFP-TRBP but not GFP-TRBP blocks the BDNF-induced decrease in miR-16-5p activity in dual-fluorescence sensor assay. Hippocampal neurons were transfected with 200ng miR16- or control-sensor (see Fig 5A) plus 50ng GFP, 400ng GFP-TRBP or 400ng mGFP-TRBP. Neurons were treated with BDNF or vehicle control prior to fixation and immunostained with anti-GFP antibody. BDNF led to a decrease in miR-16-5p activity in GFP-transfected neurons (p=0.03, n=4, t-test type 3), which was significantly different from mGFP-TRBP-expressing neurons (p=0.04, n=4, t-test type 2, error bars are s.d.).",
    "ncbi_link": "TRBP: 
miR-16-5p: 100313997
miR16: 100313997"
  },
  {
    "caption": "A Phenotypes of WT, dja6, dja5, dja6 dja5 and RNAi seedlings on MS medium with 2%  sucrose. Scale bars = 0.5 cm.",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "B,C  Phenotypes and chlorophyll fluorescence images of 6-week-old WT, dja6 dja5 and complemented plants (B) on MS medium with 2% sucrose, scale bars = 0.5 cm; WT, dja6, dja5 and RNAi mutants (C) grown on soil,­­­ scale bars = 1 cm. Fluorescences in (B) and (C) were measured with the FluorCam700MF and visualized using a pseudocolor index as indicated on the right.",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "D Chlorophyll content of total leaves in 6-week-old WT, dja6, dja5, dja6 dja5  and RNAi seedlings. FW, fresh weight. Data are the means ± SEM (n = 7 biological replicates).",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "E The ultrastructure of plastids from WT, dja6, dja5,  dja6 dja5 and RNAi mutants. T, thylakoids. Scale bars = 0.2 μm.",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "A, B Total protein was extracted from 4-week-old WT,  dja6, dja5, dja6 dja5 and RNAi  seedlings, respectively. WT and dja6 dja5 used in (A) were grown on MS medium with 2% sucrose, while WT, dja6, dja5 and RNAi  mutants used in (B) were grown on soil. 10 μg protein was loaded, except for detection with anti-SUFE1 and anti-SUFA antiserum, for which 25 μg were loaded. Specific bands were identified by immunoblotting and by their molecular weight, and are indicated by asterisks. Designations of photosynthetic protein complexes and their diagnostic components are labeled on the left and right, respectively. The Fe-S types of Fe-S proteins are shown in parentheses. Actin  served as controls to normalize protein levels. For each protein, three independent biological replicates were performed and a representative one is shown.",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "A-C Metal concentrations in the WT,  dja6 dja5 and RNAi mutants. Fe concentrations in total  leaves (A and B) and total chloroplast (C) from 4-week-old WT, dja6 dja5 and RNAi mutants were quantified by inductively coupled plasma mass spectrometry, and are shown as means ± SEM (n = 3 biological replicates) of μg g-1 dry weight  (DW). WT and RNAi mutants used in (A and C) were grown on soil, while WT and dja6 dja5 seedlings used in (B) were grown on MS medium with 2% sucrose. Similar results were obtained in two additional independent biological experiments. Asterisks indicate significant differences from the value of WT (two-sample Student's t-test; *, P < 0.05; **, P < 0.01; ***, P < 0.001).",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "D Volcano plot of the result from quantitative transcriptome profiling in WT and dja6 dja5 mutant. Statistical analysis was performed using Student's t-test. Data on the X-axis represent the Log2-ratio of FC (fold change) between the absolute abundances of transcripts identified from dja6 dja5 against WT. The Y-axis represents the Log10 of FDR (false discovery rate). All DEGs (differentially expressed genes) with FDR < 0.01 and FC > 2 are marked in grey, while all iron-related DEGs with FDR < 0.01 and FC > 2 are marked in red. The iron-related DEGs labeled with red dots within the black boxes are referred to in the text. All data are based on three biological replicates.",
    "ncbi_link": "dja6: 816768
dja5: 830157"
  },
  {
    "caption": "C Phenotypes and chlorophyll fluorescence images of 6-week-old WT and 35Spro:SynDJA6-FLAG/dja6 dja5 transgenic plants  grown on soil. Scale bars = 1 cm.",
    "ncbi_link": "FLAG: 
dja6: 816768
DJA6: 816768
dja5: 830157"
  },
  {
    "caption": "D Expression of FLAG-tagged SynDJA6 in 35Spro:SynDJA6-FLAG/dja6 dja5 transgenic plants. Total leaf  extracts (100 μg proteins) from WT and transgenic  seedlings were loaded. FLAG-tagged SynDJA6 is indicated by asterisk.",
    "ncbi_link": "dja6: 816768
DJA6: 816768
dja5: 830157"
  },
  {
    "caption": "A, B Detection of γb palmitoylation through the  biotin-switch assay in  N. benthamiana. The γb-3xFlag and γb3CS-3xFlag proteins were treated with (Hyd+) or without (Hyd-) hydroxylamine, the thioester  cleavage reagent. Lanes labelled ' Palmitoylation ' show γb-3xFlag or  γb3CS-3xFlag  amounts recovered from the neutravidin  beads. The loading controls indicate sample loading onto the neutravidin  beads. Data information: In (A, representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "A Effects of γb palmitoylation on BSMV  replication. Movement-deficient BSMV  (RNAα  + RNAγ/RNAγ3CS) was agroinfiltrated into N. benthamiana leaves. At 3 dpi, total protein and RNA were extracted for Western and Northern blot analyses. Antibodies and probes used for molecular analyses are indicated on the right of each panel. Actin  was used to monitor equal protein loading, and methylene blue-stained rRNAs  served as RNA loading controls. Data information: representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "rRNAs: 
RNAα: 962673
RNAγ: 962674"
  },
  {
    "caption": "B  Western blot  analyses of chloroplast localization  of γb  and  γb3CS. Transiently expressed αa-GFP  in intact chloroplasts  isolated from BSMVγb-3xFlag- or  BSMV3CS-3xFlag-infected N. benthamiana leaves at 4 dpi. Detection of γb-3xFlag and γb3CS-3xFlag with an anti-Flag  antibody; TGB1  analysis with an anti-TGB1  antibody; αa-GFP  detection with an anti-GFP  antibody. NTRC  was a loading control for intact chloroplasts Phosphoenolpyruvate carboxylase (PEPC) was used to assess cytosolic  contamination of isolated chloroplasts. Data information: , representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "Flag: 
GFP: 
αa: 962673
γb: 962674"
  },
  {
    "caption": "C Subcellular localization   of γb-GFP  and γb3CS-GFP  in N. benthamiana epidermal leaf  cells. The first and second rows show  subcellular localization  of γb-GFP  and γb3CS-GFP  transient expression in leaves. The third and fourth rows show localization  of γb-GFP  and γb3CS-GFP  in BSMVγb-GFP- and BSMV3CS-GFP-infected leaves  at 3 dpi. Figures on the right indicate the normalized fluorescence intensities of the GFP  (green) or the chloroplast  autofluorescence (red) channels along the dashed white lines shown in the merged images of the left panel. Scale bars, 20 μm. Data information: representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "GFP: 
γb: 962674"
  },
  {
    "caption": "D Subcellular localization  of γb-GFP  or γb3CS-GFP  in isolated N. benthamiana protoplasts   harvested at 3 dpi. The fifth and sixth columns show γb localization  in BSMVγb-GFP- (movement-deficient) N. benthamiana protoplasts  after treatment with 200 μM 2-BP inhibitor. The released protoplasts  were collected after 48 h incubation in DMSO  or 2-BP followed by confocal microscopy visualization. Figures at the bottom indicate the normalized fluorescence intensities of the GFP  (green) and the chloroplast   autofluorescence (red) channels along the dashed white lines in the merged images above. Scale bars, 20 μm. Data information: representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "GFP: 
γb: 962674"
  },
  {
    "caption": "A Effects of γb palmitoylation on  virus cell-to-cell movement    at 3 dpi with the BSMV  duplex fluorescence (dfBSMV) reporter system The dfBSMVmγb mutant control contains an ATG substitution of the γb  initiation codon Red fluorescence produced from the mCherry  expression cassette illustrates the primary infection foci, whereas GFP  fluorescence outside the red region shows invaded cells surrounding the primary infection foci. Fluorescence was evaluated by confocal microscopy. Scale bars, 100 μm. B Quantification of virus movement  in Panel A. To determine the movement capacity of the viruses depicted in each panel, the mCherry  and GFP  fluorescent intensities were first determined by ImageJ software. Then, the intensities within the secondarily invaded cells were divided by the fluorescent mCherry  plus the GFP  intensities in the primary infection foci (n = 10). The Y-axis indicates the relative sizes of the green areas in comparison to that of the red-colored areas. Data information: In (A, representative data are shown and three biological replicates had similar results. In (B), the box boundaries indicate the upper (25th percentile) and lower (75th percentile) quartiles, whiskers indicate minimum and maximum values, central band indicates the median. Letters in the chart denote statistically significant differences among groups according to the Duncan's multiple range test (p < 0.05).",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "D Biotin-switch assay  to access palmitoylation of γb  in BSMV-infected N. benthamiana leaves  at different timepoints. BSMVγb-3xFlag was treated with the hydroxylamine  (Hyd+) thioester  cleavage reagent. Equal sample amounts used for palmitoylation analyses were monitored by Western blot  analysis with an anti-Flag  antibody. Data information: In representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "Flag: 
γb: 962674"
  },
  {
    "caption": "E Subcellular localization  of BSMVγb-GFP and BSMV3CS-GFP in  N. benthamiana leaf epidermal cells. The mCherry-HDEL    and mTalin-RFP  reporters were used as markers to indicate the  ER and actin localization  Figures at the bottom indicate the normalized fluorescence intensities of the GFP  and mCherry  channels along the white dashed lines in the merged images above. Scale bars, 10 μm. Data information: In E), representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "GFP: 
γb: 962674"
  },
  {
    "caption": "A BiFC co-localization analyses of αa  and TGB1  in N. benthamiana leaf  cells  at 3 dpi.  YFPn  and YFPc was fused to the TGB1  and the αa  proteins, respectively. Combinations of γb, γb3CS and the TBSV P19  control are shown above the micrographs. YFP  signals were visualized by confocal microscopy at 3 dpi and depicted as a false-green color. Scale bars, 30 μm. B Quantification of the numbers of YFP  foci per visual field (n = 10). Data information: In (A, , representative data are shown and three biological replicates had similar results. In (B, the box boundaries indicate the upper (25th percentile) and lower (75th percentile) quartiles, whiskers indicate minimum and maximum values, central band indicates the median. Letters in the chart denote statistically significant differences among groups according to the Duncan's multiple range test (p < 0.05).",
    "ncbi_link": "γb: 962674
P19: 1493957"
  },
  {
    "caption": "C Co-IP assays to determine in vivo interactions  between TGB1 and γb  or γb3CS. N. benthamiana leaf  tissues co-agroinfiltrated with RNAα, RNAγγb-GFP  or RNAγ3CS-GFP, and TGB1-3xFlag plasmids were harvested at 3 dpi. Total proteins were immunoprecipitated  with anti-Flag  beads. Input and immunoprecipitated  proteins (IP) were analyzed by Western blotting  with anti-GFP  or anti-Flag  antibodies.",
    "ncbi_link": "Flag: 
GFP: 
RNAα: 962673
TGB1: 962677
RNAγ: 962674
γb: 962674"
  },
  {
    "caption": "D Confocal microscopy  analyses showing RFP-TGB1 localization  at the  chloroplast periphery  in N. benthamiana leaves  agroinfiltrated with αa-GFP  and CFP-γb plasmids. CFP-γb  or CFP-γb3CS were co-expressed with RFP-TGB1  and αa-GFP  in  N. benthamiana leaves. Chloroplast  autofluorescence was displayed in false pink color. The third and fourth rows show leaves treated with 400 μM 2-BP inhibitor or the DMSO  control at 1 dpi. Two days later, confocal microscopy  observations of RFP-TGB1, αa-GFP, and CFP-γb  were performed. Figures on the right indicate the normalized fluorescence intensity of GFP, RFP, and CFP  channels along the white dashed line in the merged confocal images. Scale bars, 10 μm. Data information: In , representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "CFP: 
GFP: 
RFP: 
αa: 962673
TGB1: 962677
γb: 962674"
  },
  {
    "caption": "G Chloroplast  extraction experiment for detection of TGB1 chloroplast localization. Plasmids harboring αa-GFP  and RFP-TGB1  were co-infiltrated into  N. benthamiana along with CFP-γb  or CFP-γb3CS. Intact chloroplast  preparations isolated from infiltrated  N. benthamiana leaves  at 4 dpi were subjected to Western blot  analyses. RFP-TGB1  was analyzed with an anti-TGB1  antibody. The αa-GFP, CFP-γb, and CFP-γb3CS proteins were detected with an anti-GFP  antibody. NTRC  was the loading control for the chloroplast  preparations Phosphoenolpyruvate carboxylase (PEPC) served as a control to assess cytosolic  contamination of isolated chloroplasts. Data information: In G), representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "CFP: 
GFP: 
RFP: 
αa: 962673
TGB1: 962677
γb: 962674"
  },
  {
    "caption": "B Analysis of γb palmitoylation in  NbPAT15- or NbPAT21-silenced N. benthamiana  plants. NbPAT15 and NbPAT21 were silenced by intron-spliced hairpin RNA-mediated RNAi approaches The γb-3xFlag   plasmid was agroinfiltrated into the leaves, followed by  biotin-switch assays  at 3 dpi. Data information: In (B representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "Flag: 
γb: 962674
PAT15: 109211026
PAT21: 109240893"
  },
  {
    "caption": "C Effects of γb palmitoylation by NbPAT15  or NbPAT21  on BSMV cell-to-cell movement. Infiltrated leaves  were observed by confocal microscopy at 3 dpi. Red fluorescence produced from the mCherry  expression cassette shows the primary infection foci, and GFP  fluorescence outside the red regions shows virus spread into secondary infected cells. Scale bars, 100 μm. Data information: In C), representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "PAT15: 109211026
PAT21: 109240893"
  },
  {
    "caption": "A, B BiFC assays  to identify interactions  of γb  with NbPAT15  and NbPAT21 during BSMV  infection in  N. benthamiana at 3 dpi. PAT15-YFPn and PAT21-YFPn were co-expressed with BSMVγb-YFPc. Chloroplast  autofluorescence is depicted as a false red color and mCherry-HDEL   provides the ER  marker. Figures on the right show the normalized fluorescence intensities of GFP, mCherry  and the chloroplast  autofluorescence channels along the white dashed lines in the merged images. Scale bars, 20 μm. Data information: In (A, B, representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "YFP: 
γb: 962674
PAT15: 109211026
PAT21: 109240893"
  },
  {
    "caption": "C Co-localization  analyses of αa-GFP, RFP-TGB1, and CFP-γb  in N. benthamiana leaves  at 3 dpi. Mixtures of A. tumefaciens containing αa-GFP, RFP-TGB1, and CFP-γb  were infiltrated into  NbPATs-silenced N. benthamiana leaves  or the non-silenced TRV:GUS control. Chloroplast  autofluorescence is displayed as a false pink color. Figures on the right show the normalized fluorescence intensities of GFP, RFP, CFP  and the chloroplast  autofluorescence channels along the white dashed lines in the merged images. Scale bars, 10 μm. Data information: In , representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "CFP: 
GFP: 
RFP: 
αa: 962673
TGB1: 962677
γb: 962674
GUS: 946149"
  },
  {
    "caption": "D Co-IP assays of interactions between γb  and TGB1  in NbPAT15- and NbPAT21-silenced N. benthamiana leaves, TRV:GUS  and TRV:GUS combined with the  2-BP inhibitor provided positive and negative controls, respectively. The silenced leaves  were inoculated with BSMV3xFlag-TGB1/γb-GFP mixtures (RNAα + RNAβ3xFlag-TGB1 + RNAγγb-GFP) and harvested at 3 dpi. Total proteins were immunoprecipitated  with anti-Flag  beads. Input and IP  proteins were analyzed by Western blotting with anti-GFP or anti-Flag  antibodies. E Average amounts of RFP-TGB1  foci co-localizing with αa-GFP and CFP-γb  at the  chloroplast peripheries  shown in panel C (n = 12). Data information: In E), representative data are shown and three biological replicates had similar results. In (E), the box boundaries indicate the upper (25th percentile) and lower (75th percentile) quartiles, whiskers indicate minimum and maximum values, central band indicates the median. Letters in the chart denote statistically significant differences among groups according to the Duncan's multiple range test (p < 0.05).",
    "ncbi_link": "Flag: 
GFP: 
RNAα: 962673
TGB1: 962677
RNAβ: 962679///962678///962677
RNAγ: 962674
γb: 962674
PAT15: 109211026
PAT21: 109240893
GUS: 946149"
  },
  {
    "caption": "C Aqueous two-phase partitioning of γb PM localization. The microsomal  pellet from  BSMVγb-GFP-infected leaves  was obtained by ultracentrifugation at 100,000 g, and the  two-phase fractionation procedure was used to separate the plasma membrane (upper phase) from other  cellular membranes (lower phase). H+-ATPase is a PM  marker.",
    "ncbi_link": "GFP: 
γb: 962674"
  },
  {
    "caption": "D PM  associations of γb-GFP  and  γb3CS-GFP  in N. benthamiana protoplasts. The first and second columns show localization  of γb  at 3 dpi after infiltrations for transient expression of γb-GFP  and γb3CS-GFP. The third and fourth columns show γb localization in BSMVγb-GFP and BSMV3CS-GFP-infected leaves. PIP2A  provided a PM  marker (Nelson et al., 2007). Figures below the confocal  images show the normalized fluorescence intensities of the GFP  and mCherry  proteins along the white dashed lines in the merged images. Scale bars, 10 μm. Data information: In D, , representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "GFP: 
γb: 962674"
  },
  {
    "caption": "F Western blot  detection of BSMV  accumulation in  N. benthamiana plants. A. tumefaciens  mixtures harboring RNAα  and RNAβmTGB2, along with RNAγ,  RNAγγb-ROP, or RNAγγb-mROP, were agroinfiltrated into  N. benthamiana leaves. Western blotting to detect virus accumulation at 3 dpi used anti-TGB1  or anti-CP  antibodies. Actin  provided loading controls.",
    "ncbi_link": "ROP: 
RNAα: 962673
TGB2: 962678
RNAβ: 962679///962677///962678
RNAγ: 962674
γb: 962674"
  },
  {
    "caption": "G Analysis of the effects of enhanced PM  association of γb   on  cell-to-cell virus movement   with the BSMV   duplex fluorescence (dfBSMV) reporter system. Mixtures of A. tumefaciens  containing dfBSMV, dfBSMVγb-GFP-ROP, and dfBSMVγb-GFP-mROP were infiltrated into N. benthamiana leaves. Infiltrated leaves  were observed by confocal microscope at 3 dpi. Scale bars, 100 μm. (n = 6). Data information: In G), representative data are shown and three biological replicates had similar results. In (G), the box boundaries indicate the upper (25th percentile) and lower (75th percentile) quartiles, whiskers indicate minimum and maximum values, central band indicates the median. Letters in the chart denote statistically significant differences among groups according to the Duncan's multiple range test (p < 0.05).",
    "ncbi_link": "GFP: 
ROP: 
γb: 962674"
  },
  {
    "caption": "B Co-IP  analyses to analyze interactions  of NbREM1 with γb  or γb3CS in  N. benthamiana leaf  tissues infiltrated with A. tumefaciens  mixtures containing movement-deficient BSMV plasmids (RNAα  + RNAγγb-GFP  or RNAγ3CS-GFP) and NbREM1-3xFlag. Total proteins were extracted at 3 dpi and immunoprecipitated with anti-Flag  beads. Input and immunoprecipitated  proteins (IP) were analyzed by Western blot  analyses with an anti-GFP  or anti-Flag  antibodies. Data information: In B, , representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "Flag: 
GFP: 
REM1: 
RNAα: 962673
RNAγ: 962674
γb: 962674"
  },
  {
    "caption": "D Analysis of the cleaved 5(6)-carboxyfluorescein (CF) movement in N. benthamiana leaves. RNAα  + RNAγ/RNAγ3CS were co-infiltrated into transiently overexpressed  NbREM1 N. benthamiana leaves, and 1 μL CFDA was loaded onto the adaxial leaf  blade surface and incubated for 5 min followed by confocal  analysis at 3 dpi. The areas of dye diffusion are marked by dashed white circles. Scale bars, 100 μm. Data information: In D, representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "REM1: 
RNAα: 962673
RNAγ: 962674"
  },
  {
    "caption": "H Aniline blue staining  of callose  in leaves with different treatments above the panel in NbPAT15 and NbPAT21 RNAi plants. Scale bars, 20 μm. Data information: In H), representative data are shown and three biological replicates had similar results.",
    "ncbi_link": "PAT15: 109211026
PAT21: 109240893"
  },
  {
    "caption": "(A) Immunoblot with anti-TG2 or anti-β-actin as loading control in in whole lysates from small intestine homogenates of CftrF508del/F508del and wild-type (CftrWT) mice (n=5 per group) and densitometric analysis of immunoblots. Mean ± SD of triplicates of independent pooled samples. **p<0.01 (Student's t test). Data information: The blots are representative of one experiment for group of treatment.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(B) Detection of NLRP3 expression (top) and caspase-1 cleavage (bottom) by immunoblot of whole lysates from small intestine homogenates of CftrWT and CftrF508del/F508del mice (n= 5) and densitometric analysis of immunoblots. Mean ± SD of triplicates of independent pooled samples. **p<0.01 CftrWT vs CftrF508del/F508del (Student's t test). Data information: The blots are representative of one experiment for group of treatment.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(C) Protein levels of IL-17A and IFN-γ from small intestine homogenates of CftrWT and CftrF508del/F508del (n= 10). Mean ± SD of triplicates of independent pooled samples. ***p<0.001 CftrWT vs CftrF508del/F508del (Student's t test).",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(D) IL-15 mRNA (left) and protein (right) levels in small intestine homogenates from CftrF508del/F508del, Cftr-/- or their CftrWT littermates (n= 10 per group). Mean ± SD of triplicates of independent pooled samples. **p<0.01 CftrF508del/F508del vs CftrWT(FVB/129), or °°p<0.01 Cftr-/- vs CftrWT(B6.129P2) (ANOVA, Bonferroni post hoc test).",
    "ncbi_link": "Cftr: 12638
IL-15: 16168"
  },
  {
    "caption": "(E) IL-15 mRNA levels in small intestine homogenates from CftrWT mice or CftrF508del/F508del or TG-/-/CftrF508del/F508del or TG-/- mice (n= 10 per group). Mean ± SD of triplicates of independent pooled samples. ***p<0.001 vs CftrWT, °°p<0.01, ##p<0.01 vs CftrF508del/F508del (ANOVA, Bonferroni post hoc test).",
    "ncbi_link": "Cftr: 12638
IL-15: 16168
TG: 21817"
  },
  {
    "caption": "(F) Effects of 4 weeks of oral administration of gliadin on IL-15, IL-17A and IFN-γ protein levels in small intestine homogenates from CftrF508del/F508del and CftrWT mice (n =10 mice per group of treatment). Mean ± SD of triplicates of independent pooled samples. **p<0.01, ***p<0.001 (CftrF508del/F508del vs CftrWT mice prior gliadin challenge), °°°p<0.001 (CftrF508del/F508del mice vs CftrF508del/F508del mice after gliadin challenge), (ANOVA, Bonferroni post hoc test).",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(G-I) BALB/c mice (G) fed with a gluten-free diet for at least 3 generations, or (H) NOD or (I) NOD-DQ8 mice orally challenged with vehicle or gliadin for 4 weeks (5 mg/daily for one week and then 5 mg/daily thrice a week for 3 weeks). Representative traces of CFTR-dependent Cl- secretion measured by forskolin (Fsk)-induced increase of chloride current (Isc (μA/cm2)) in small intestines mounted in Ussing chambers; quantification of the peak CFTR inhibitor 172 (CFTRinh172)-sensitive Isc (∆Isc) in tissue samples (n=3 independent experiments). Mean±SD of samples assayed; **p<0.01, ***p<0.001 vs challenged with gliadin (Student's t test).",
    "ncbi_link": "DQ8: "
  },
  {
    "caption": "Incubation of Caco-2 cells with P31-43, in the presence or absence of pre-treatment with TG2 inhibitor Z-DON, TG2-siRNA Immunoprecipitation in non-reducing and non-denaturing conditions of CFTR protein and immunoblot with anti-isopeptide glutamime-lysine and CFTR",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "Caco-2 cells incubated with P31-43 in the presence or absence of VX-770 (G) IL-15 production (quantified by specific ELISA) in CFTR-WT Caco-2 cells treated or not with P31-43 (left) or in Caco-2CFTR-KO cells (right), in the presence or absence of VX-770. Mean ± SD of triplicates of independent experiments. ***p<0.001 vs untreated and °°°p<0.001 vs CFTR-WT Caco-2 cells treated with P31-43+VX-770 (ANOVA, Bonferroni post hoc test). **p<0.01 vs Caco-2 CFTR WT (Student's t-test).",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "Caco-2 cells incubated with P31-43 in the presence or absence of VX-770 (H) Caco-2 or Caco-2CFTR-KO cells in the presence or absence of pre-treatment with VX-770. Immunoblot of phERK1\2 or β-actin (left); densitometric analysis of protein levels (right). Mean ± SD of triplicates of independent experiments. *p<0.05 (Student's t-test). Data information: The blots are representative of one experiment for group of treatment.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "BALB/c mice fed with a gluten-free diet for at least 3 generations, orally challenged with vehicle or gliadin for 4 weeks (5 mg/daily for one week and then 5 mg/daily thrice a week for 3 weeks) in the presence or absence of intraperitoneal VX-770 administered 15 minutes prior gliadin challenge (n=10 mice per group of treatment). Transcript level of Rorc and Tbet (G) from small intestine homogenates. Mean ± SD of triplicates of independent pooled samples. ***p<0.001 or ****p<0.0001 gliadin vs VX-770+gliadin (ANOVA, Bonferroni post hoc test).",
    "ncbi_link": "Rorc: 19885
Tbet: 57765"
  },
  {
    "caption": "(L) IFN-γ release (ELISA) into culture supernatants by PBMC from 3 celiac patients cultured in the lower compartment of a bidimensional co-culture model upon a 24 h challenge of confluent Caco-2CFTR-KO cells in the upper compartment with a combination of P31-43 and P57-68 in the presence or absence of VX-770, as in J and K. *p<0.05, medium vs P57-68/P31-43 combination (n=3) (ANOVA, Bonferroni post hoc test).",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": " (A) Immunofluorescence analysis of HeLa cells transfected with either a non-target dsRNA (NT) or one of the three siRNAs targeting LETM1 (siR1, siR2 or siR3) and labeled with anti-TOM20 antibody. In siR1 treated cells, the mitochondria formed a 'honeycomb' of swollen distinct organelles; siR3 resulted in giant organelles with a central region distinguished by reduced TOM20; siR2, produced relatively little swelling and the mitochondrial network was generally well preserved. The pronounced swelling induced by siR1 significantly increased circularity (p = 2.32E-58) (ImageJ analysis), siR1 circularity = 0.683 ±0.012 compared with 0.414 ±0.008 for the NT; where 1 = a perfect circle. Over 150 mitochondria were quantified in each cell type; data are means ± SEM. Scale bar represents 12 µm in the main images and 4 µm in offset magnification ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (D) Representative immunoblots for the OXPHOS proteins NDUFB8 and COII of HeLa cells transfected with NT or siLETM1 (siR1, siR2 or siR3). Vinculin and GAPDH are shown as loading controls. The mean relative abundances for respiratory subunits COII and NDUFB8 are shown beneath the blots. Data are expressed as mean ± SEM of n=8 independent experiments ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (E) Mitochondrial oxygen consumption rate (OCR) measured using a Seahorse flux analyzer before (basal) and after the addition (maximal) of the uncoupler FCCP, in HeLa cells treated with NT or siLETM1 (siR1 or siR2). Data are means ± SEM of n=5 experiments ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (A) LETM1 expression was suppressed in HeLa cells by transfection with targeted siRNAs (siR1, siR2 or siR3). A non-target dsRNA (NT) served as control. Cells were fixed and immunolabeled with anti-DNA antibody (green). A higher magnification of selected mtDNA foci is shown beside each picture. (B) Quantification of cells in (A) displaying mtDNA abnormalities. At least 50 cells per siRNA were counted from 4 (siR2) and 5 (siR1 or siR3) independent experiments. Data are expressed as means ± SEM. ***P<0.001 (One-way ANOVA) ",
    "ncbi_link": "mtDNA: 
LETM1: 3954"
  },
  {
    "caption": " (A) Steady state levels of LETM1 protein in fibroblasts from controls (C1-C3), WHS LETM1+/- (S1, S3, S4) and S5 the sole case of WHS in this study whose deletion does not encompass LETM1 (boxed in blue). GAPDH is shown as a loading control ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (B) Immunofluoresence analysis of control (C1), and WHS LETM1+/- S1-S4, fibroblasts with anti-TOM20 antibody. Scale bars are 8 µm in the main images and 3 µm in offset merged magnifications ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (C) Electron micrographs of controls (C1 and C2) and WHS LETM1+/+ (S5) cells; side panels show zooms. Scale bar: 0.2 µm. Black arrows indicate the areas shown offset at higher magnification (D) Electron micrographs of WHS LETM1+/- S1, S3 and S4 cells. Black arrows indicate elongated and branched mitochondria; side panels show magnifications. Scale bar: 0.2 µm ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (B) Left panel: immunoblot analysis of total PDH protein levels and the inactive phosphorylated (repressed form), PDHS293, in control (C1, C3), WHS LETM1+/- (S1, S3, S4) and WHS LETM1+/+ (S5) fibroblasts. Center and Right panels: Immunoblot analysis of PDK3 in control (C1-C3), WHS LETM1+/- (S1, S3 and S4) and WHS LETM1+/+ (S5) fibroblasts ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (C) Left panel: change in cell confluence of control (C1-C3), WHS LETM1+/- (S1-S4) and WHS LETM1+/+ (S5) fibroblasts grown in BHB over the course of 188 h. Data are expressed as means ± SEM of n=3 independent experiments. Right panel: images of control and WHS LETM1+/- S4 cells growing either in the presence of 25 mM glucose (HG) or BHB (KB) for 6 days. Scale bar 300 µm ",
    "ncbi_link": "LETM1: 3954"
  },
  {
    "caption": " (E) Proportion of cells that displayed mtDNA aggregation during the KB treatment (panel i - control cells (C1, C2), and WHS LETM1+/+ (S5) fibroblasts; panel ii - LETM1+/- (S1, S2, S4) fibroblasts). At least 50 cells per cell line were counted at the indicated time points. Data are expressed as mean ± SEM of n=3 independent experiments ",
    "ncbi_link": "mtDNA: 
LETM1: 3954"
  },
  {
    "caption": "S. indica colonization of Arabidopsis dorn1-3 mutant and the parental Col-0aq lines quantified by qPCR at 3, 5, 7 and 10 dpi. The ratio of fungal (SiTEF) to plant (AtUBI) amplicons representing fungal colonization levels in plant root tissue was calculated using gDNA as template and the 2-ΔCT method. Error bars represent standard error of the mean of three technical replicates. The experiment was repeated 3 times for 3, 5 and 7 dpi with similar outcomes.",
    "ncbi_link": "AtUBI: 
SiTEF: 
dorn1: 836152"
  },
  {
    "caption": "Transcript levels of S. indica E5′NT during colonization of barley and Arabidopsis at different symbiotic stages and in axenic culture. Error bars represent standard error of the mean of three independent biological replicates. CM = complex medium.",
    "ncbi_link": "E5′NT: "
  },
  {
    "caption": "Ecto-5′-nucleotidase activity measured in membrane protein preparations of Arabidopsis plants expressing Pro35S::E5′NT (#303), Pro35S::SPE5′NT:mCherry:E5′NTwoSP (#304) or Pro35S::mCherry (#305). E5′NT activity was measured after incubation with 100 µM of either ATP, ADP or AMP. In the membrane protein preparations from Pro35S::E5′NT (#303) lines phosphate release was specifically increased upon incubation with purines. Error bars represent the standard error of the mean from three technical repetitions. The coomassie stained SDS-PAGE shows the protein pattern of the membrane fractions for the individual transgenic lines. Equal volumes were loaded. The experiment was repeated two times with similar results.",
    "ncbi_link": "E5′NT: 
mCherry: "
  },
  {
    "caption": "Confocal microscopy images of Arabidopsis roots expressing either cytosolic mCherry (#305) or Pro35S::SPE5′NT:mCherry:E5′NTwoSP (#304) showing secretion of the E5′NT fusion protein. mCherry images show z-stacks of 14 image planes of 1 µm each. Scale bar=20 µm.",
    "ncbi_link": "E5′NT: 
mCherry: "
  },
  {
    "caption": "The transgenic Arabidopsis line Pro35S::E5′NT (#303) expressing untagged full length SiE5′NT was better colonized by S. indica. Error bars of the qPCR data represent ±SE of the mean from three independent biological replicates. Asterisks indicate significance (Student's t-test, * p< 0.05).",
    "ncbi_link": "SiE5′NT: 
E5′NT: "
  },
  {
    "caption": "Expression analysis of the eATP responsive gene At1g58420 measured by qRT-PCR. Error bars represent ±SE of the mean from three independent biological replicates (independent from those shown in Fig. 2C). Letters indicate significant groups (ANOVA, p<0.01, for the line 305 p<0.05).",
    "ncbi_link": "At1g58420: 842211"
  },
  {
    "caption": "Typical retinal flat mount from Acta1GFP/+:Acta1+/+ bone marrow chimeras 20 weeks after reconstitution. Donor-derived GFP+Iba1+ cells (arrow) and GFP-Iba1+ resident microglia (asterisks) are shown. Pictures are representative for three animals from one experiment. Scale bars represents 50 µm.   Microscopy-based quantification of GFP+Iba1+ retinal microglia in the inner (IPL) and outer plexiform layer (OPL). One symbol represents one mouse. Data are presented as mean ± s.e.m.  ",
    "ncbi_link": "Acta1: 11459"
  },
  {
    "caption": "Direct fluorescence microscopic visualization for YFP (green), the macrophage marker Iba1 (red) and DAPI for the nuclei (blue) at P0. YFP+Iba1+ double-positive cells are marked by arrows. YFP-Iba1+ single-positive cells are labelled by asterisks. Representative images out of five examined animals are shown. Scale bars represents 25 µm.   Quantitative analysis of regional YFP expression in Iba1+ macrophages in TAM-induced and untreated Cx3cr1CreERT2:Rosa26-YFP mice. Bars represent means ± s.e.m. Quantification was done from three (untreated) or five (TAM) mice obtained from one (untreated) or two (TAM) independent experiments. Level of significance determined by Mann-Whitney test between TAM and untreated revealed *p < 0.05 and Kruskal-Wallis test between retina, ciliary body and cornea revealed *p = 0.0204.  ",
    "ncbi_link": "YFP: 
Cre: 2777477
Cx3cr1: 13051
Rosa26: 14910
ERT2: 5595"
  },
  {
    "caption": "Above: Representative funduscopic pictures from living healthy Cx3cr1CreERT2:Rosa26-tdTomato mice on d0. Funduscopy and red fluorescence visualize the fundus and regular distribution of tomato+ microglia before the laser-induced lesion formation. Below: Corresponding immunofluorescence pictures. Non-lesioned retina show a regular pattern of Iba1+ (green) tomato+ (red) retinal microglia while macrophages are absent on the retinal pigment epithelium (RPE) under native conditions. Pictures are representative for six mice analyzed in one experiment. Scale bars represents 50 µm. c) Above: In vivo funduscopy on d7 post lesion. Funduscopic and red fluorescence image depict the lesions (encircled with dashed white lines) and accumulation of tomato+ microglia in Cx3cr1CreERT2:Rosa26-tdTomato mice. Intraperitoneal fluorescein application was performed to label retinal vessels and areas of choroidal neovascularization. Below: Representative immunofluorescence for Iba1 (green) in Cx3cr1CreERT2:Rosa26-tdTomato mice. Resident retinal microglia are Iba1+tomato+ (asterisks) whereas blood-derived myeloid cells are Iba1+tomato- (arrows) and accumulate at sites of laser-induced CNV. Overlay is shown left. Typical pictures from six mice obtained from one independent experiment are shown. Scale bars represents 50 µm.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Cx3cr1: 13051
Rosa26: 14910
ERT2: 5595"
  },
  {
    "caption": "d) Percentage (left) and absolute numbers (right) of myeloid subsets in the retina at different time points post lesion. Red columns, red lines and red symbols represent tomato*Iba1+ microglia in Cx3cr1CreERT2:Rosa26-tdTomato mice whereas green columns, green lines and green symbols represent blood-derived tomato-Iba1+ myeloid cells. Left, Wilcoxon test at d3 (ns p = 0.0625), d28 (ns, p = 0.25) and d56 (ns p = 0.125) and paired t test at d7 (***p < 0.0001 and d14 (***p < 0.0001; right, absolute numbers Kruskal-Wallis test (tomato*Iba1+ *p < 0.05, tomato-Iba1+ ** p < 0.01). Data represent means ± s.e.m. from at least three mice per group (two to six lesion per mouse) out of one (d0, d14, d28, d56) or two (d7, d14) independent experiments. e) Distribution (left) and absolute numbers (right) of myeloid cells in the RPE at different time points following laser-induced lesion. Red columns, red lines and red symbols represent Iba1+ microglia in Cx3cr1CreERT2:Rosa26-tdTomato mice. Green columns, green lines and green symbols represent blood-derived Iba1+tomato- myeloid cells. Left, paired t test at d3, d7, d14 (**p < 0.01, ***p < 0.001), Wilcoxon test at d28 and d56 (ns p > 0.05); right, absolute numbers Kruskal-Wallis test (ns p > 0.05). Data represent means ± s.e.m. from at least three mice per group (two to six lesion per mouse) out of one (d0, d14, d28, d56) or two (d7, d14) independent experiments.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Cx3cr1: 13051
Rosa26: 14910
ERT2: 5595"
  },
  {
    "caption": "a) H2-Aa expression visualized by trajectory analysis and represented in a t-SNE plot.",
    "ncbi_link": "H2-Aa: 14960"
  },
  {
    "caption": "c) HLA-DRA mRNA expression examined by RNA-Seq via Massive analysis of cDNA ends (MACE) analysis of human formalin-fixed and paraffin-embedded (FFPE) membranes of choroidal neovascularization (CNV). Bars represent means ± s.e.m. of four investigated human samples of age-related macular degeneration associated with choroidal neovascularization and four control tissues consisting of choroid and RPE. Level of significance was calculated using DESeq (p = 3.61x10-21).",
    "ncbi_link": "HLA-DRA: 3122"
  },
  {
    "caption": "(D) Western blot analysis of a strain expressing TurboID-HA-Emc6, Bpl1-AID*-9myc and OsTIR1 which was grown overnight in SD media with or without auxin. The cells were then diluted into fresh SD media and grown to mid logarithmic phase (~4hours) with or without auxin (respectively). When required, biotin was added either 30min before harvesting, or for the entire 4hours. H3 (histone H3) is used as a loading control.",
    "ncbi_link": "9myc: 
HA: 
TurboID: 
Bpl1: 851414
Emc6: 850646
TIR1: 4335696"
  },
  {
    "caption": "(A) Fluorescence microscopy images of control or Δemc3 strains containing either Alg1 N' tagged with GFP, Gnp1 C' tagged with GFP, Pdr12 N' tagged with GFP or Pho84 C' tagged with GFP. For the Gnp1-GFP strain, the quantified signal depletion was ~10% (p < 0.0001). Topological schematics feature beneath each respective image, with predicted TMDs highlighted in blue (Weill et al, 2019). All images are from two independent biological repeats and are digitally coloured using the 'fire' lookup table (LUT) on Fiji. The same contrast settings were used for each image pair.",
    "ncbi_link": "emc3: 853628"
  },
  {
    "caption": "B-F U2OS, HCT116 p53+/+ or HCT116 p53-/- cell lysates were immunoprecipitated with control IgG, anti-NAT10 (B and F), anti-p53 (C) and anti-Mdm2 (D and E) antibodies. The immunoprecipitates were subsequently immunoblotted with the indicated antibodies.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "G Purified NAT10 was incubated with GST, GST-p53 or GST-Mdm2 proteins coupled to Glutathione Sepharose 4B. Proteins retained on the Sepharose were then analyzed by western blot using the antibodies as indicated. The amount of GST fusion proteins are shown in the lower panel.",
    "ncbi_link": "Mdm2: 4193
p53: 7157"
  },
  {
    "caption": "H Full-length GST-p53 fusion protein, its deletion mutants or GST protein was used to pull-down experiments with purified NAT10 protein. The levels of the GST fusion proteins are shown in the left panel.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "I GST pull-down assay was performed using purified GST-NAT10 deletion mutants or GST protein and overexpressed Flag-p53 or Mdm2 protein in HEK293T cells. Schematic diagram represents the constructs of GST-NAT10 deletion mutants (right panel).",
    "ncbi_link": "Mdm2: 4193
NAT10: 55226
p53: 7157"
  },
  {
    "caption": "D His-p53 or His-p53-K120R fusion protein was incubated with purified NAT10 or NAT10 GE mutant as described in Experimental Procedures. Reaction mixtures were subjected to western blot using the site specific monoclonal anti-Ac-p53-K120 antibody.",
    "ncbi_link": "NAT10: 55226
p53: 7157
p53: P04637///7157"
  },
  {
    "caption": "D U2OS cells were transfected with control or NAT10 siRNAs. Seventy-two hours later, cells were treated with cycloheximide (CHX) and harvested at the indicated time points. Proteins from cell lysates were subjected to immunoblot for the evaluation of NAT10 and p53 (upper panels). Beta-actin was evaluated as a loading control (lower panel). p53 half-life (t1/2) obtained from three independent experiments was presented as mean ± SEM at the bottom.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "G p53 and Mdm2 double null MEF cells were transfected with the indicated constructs and treated with MG132 for 4 hours before harvest. Proteins from whole cell extracts were subjected to western blot using the indicated antibodies.",
    "ncbi_link": "Mdm2: 4193
p53: 7157"
  },
  {
    "caption": "B HCT116 cells were transfected with Flag-NAT10 and harvested at indicated time points after treated with CHX. Proteins from cell lysates were immunoblotted with the antibodies as indicated (left panel). Relative Mdm2 protein levels standardized by β-actin are shown in the right. Mdm2 half-life (t1/2) obtained from three independent experiments was presented as mean ± SEM at the bottom.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "D In vitro ubiquitination was performed with recombinant GST-Mdm2 (left) or GST-Mdm2 C464A mutant (right) and Flag-NAT10 or Flag-NAT10 GE in the presence of E1, E2 and Ub in vitro as described in Experimental Procedures. The reaction products were resolved by SDS-PAGE, followed by western blot for evaluation of the indicated proteins.",
    "ncbi_link": "Mdm2: 4193
NAT10: 55226"
  },
  {
    "caption": "E Mdm2 is ubiquitinated by NAT10 in a dose-dependent manner. In vitro ubiquitination assay were carried out with Mdm2 and different doses of purified Flag-NAT10 as described in D.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "G U2OS cells transfected with NAT10 siRNA-3 (targeting 3'-UTR of NAT10 mRNA) or control siRNA were co-expressed different NAT10 deletion mutants. Cell lysates were extracted and proteins from lysates were subjected to western blot using the indicated antibodies. Relative p53 protein levels standardized by β-actin are shown in the lower.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "H In vitro ubiquitination reaction was conducted using recombinant GST-Mdm2 C464A and full-length Flag-NAT10 or Flag-NAT10-D5. Ubiquitinated Mdm2 was detected as in D.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "I HCT116 cells were transfected with the indicated constructs. Cells were harvested after CHX treatment for the indicated times and cell lysates were prepared. Mdm2 protein levels were evaluated by western blot. Relative Mdm2 protein levels standardized by β-actin are shown in the right.",
    "ncbi_link": "Mdm2: 4193"
  },
  {
    "caption": "A p21 promoter luciferase reporter plasmid was cotransfected with the indicated siRNAs into U2OS cells. Luciferase activity was determined as described in Experimental Procedure.",
    "ncbi_link": "luciferase: 
p21: 1026"
  },
  {
    "caption": "D CRISPR-Cas9 system mediated NAT10 gene editing. The genome targeting for knockdown NAT10 was performed as described in Experimental Procedures. The HCT116 NAT10 knockdown cell lines were harvested and western blot was performed on the cell lysates for the indicated proteins.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "E HCT116 Ctrl or c2-4 cells with NAT10 disruption were treated with actinomycin D and harvested at the indicated time points. Cell cycle profiles were determined by FACS. Results from three independent experiments are shown as mean ± SEM. (two-tailed Student's t test)",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "F HCT116 Ctrl cells or c2-4 cells with NAT10 disruption were treated with actinomycin D Cells were harvested at the indicated time points and lysed. The total proteins were analyzed by western blot using the indicated antibodies.",
    "ncbi_link": "NAT10: 55226"
  },
  {
    "caption": "B) quantitative results (B) of DNA 6mdA in [15N5]-rA-treated mES cells after Adal knockdown for 7 days. Two independent biological replicates.",
    "ncbi_link": "Adal: 75894"
  },
  {
    "caption": "D) quantification (D) of genomic 6mdA in Adal-/- mES cells treated with [15N5]-rA for 3 days. Error bars = s.d., three independent biological replicates.",
    "ncbi_link": "Adal: 75894"
  },
  {
    "caption": "(E) The relative levels of Adal in mES, C2C12, and NIH3T3 cells against reference gene TUBB.",
    "ncbi_link": "Adal: 75894
TUBB: 110070"
  },
  {
    "caption": "C) the quantitation (C) of intracellular free [D3]-m6rA-related nucleotides in WT and Adal-/- mES cells. Total free [D3]-m6rA = Free [D3]-m6rA + [D3]-m6rAMP + [D3]-m6rADP + [D3]-m6rATP. Error bars = s.d., three independent biological replicates. *The standard was not labeled with heavy stable isotope.",
    "ncbi_link": "Adal: 75894"
  },
  {
    "caption": "E) quantitation (E) of intracellular free [D3]-6mdA-related nucleotides in WT and Adal-/- mES cells. The cells were treated with [D3]-methionine for 7 days. Total free [D3]-6mdA = Free [D3]-6mdA + [D3]-6mdAMP + [D3]-6mdADP + [D3]-6mdATP, Error bars = s.d., three independent biological replicates. *The standard was not labeled with heavy stable isotope. ND, not detected.",
    "ncbi_link": "Adal: 75894"
  },
  {
    "caption": "The western blot analysis of flag-tagged gene overexpression in Adal-/- mES cells (A) and NIH3T3 cells (B) overexpressing ADK, APRT, AK1 or NDPK gene.",
    "ncbi_link": "flag: 
Adal: 75894
ADK: 11534
AK1: 11636
APRT: 11821
NDPK: 56520"
  },
  {
    "caption": "(C) The quantification of genomic 6mdA in [15N5]-rA-traced Adal-/- mES cells overexpressing flag-tagged ADK, APRT, AK1 or NDPK gene for 7 days. (D) The quantification of genomic 6mdA in NIH3T3 cells overexpressing ADK, APRT, AK1 or NDPK gene. [15N5]-rA treatment began at 24 h after plasmid transfection and lasted for 72 hours. Two technical replicates.",
    "ncbi_link": "flag: 
Adal: 75894
ADK: 11534
AK1: 11636
APRT: 11821
NDPK: 56520"
  },
  {
    "caption": "The knockdown of Ak1 leads to a significant decreased i6mdA in NIH3T3 cells. western blot (F) were applied to determine the knockdown of Ak1 in NIH3T3 cells. Two independent biological replicates. (G) The quantitation of misincorporated 6mdA in Ak1-knockdown cells. [15N5]-rA treatment began at 24 h after siRNA transfection and lasted for 48 hours. Error bars = s.d., three technical replicates.",
    "ncbi_link": "Ak1: 11636"
  },
  {
    "caption": "(D) Cells treated or not treated with Dynasore or transfected with Dynamin K44A mutant or AP2 siRNA were fixed and then analyzed by TIRF microscopy. Pictures are at the same magnification and brightness. Cells transfected with Dynamin mutant were identified by abnormal transferrin accumulation at the plasma membrane.",
    "ncbi_link": "AP2: 1173
Dynamin: 1785"
  },
  {
    "caption": "(I) HeLa cells were transfected with pEGFP-RAB11 or pEGFP-Myosin Vb tail (MVb) and incubated during the last 16 hr with Bafilomycin A1 (Baf) or DMSO and processed for LC3-II western blot. Control cells were transfected with pEGFP empty vector.",
    "ncbi_link": "MVb: 4645
Myosin Vb: 4645
RAB11: 9230///8766"
  },
  {
    "caption": "(J) HeLa cells were transfected with ATG16L1-mStrawberry and RAB11-EGFP or MVb tail-EGFP. The size of ATG16L1 vesicles was scored in RAB11 and MVb tail overexpression conditions. The inserts show just the ATG16L1 vesicles as quantified in histogram. Error bar, SEM. ∗∗∗p<0.001.",
    "ncbi_link": "MVb: 4645
RAB11: 9230///8766"
  },
  {
    "caption": "(L) HeLa cells were transfected as in (C) and labeled for mATG9. Histogram and the inserts show the correlation between ATG16L1 and mATG9 in RAB11 and MVb tail overexpression conditions (Pearson's coefficient). Error bar, SEM. ∗∗∗p < 0.001.",
    "ncbi_link": "MVb: 4645
RAB11: 9230///8766"
  },
  {
    "caption": "(B) HeLa cells transfected with control or VAMP3 siRNA (oligo A) for 4 days were treated during the last 16 hr with Bafilomycin A1 (Baf A1) or DMSO (basal) and processed for LC3-II western blots.",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(C) Endogenous LC3 immunocytochemistry in HeLa cells transfected with control or VAMP3 siRNA for 4 days. The histogram shows the number of vesicles (LC3 positive) in a minimum of 30 cells. Error bar, SEM. ∗∗∗p < 0.001.",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(A-C) HeLa cells transfected with control, VAMP3 siRNA for 4 days were transfected during the last 20 hr with ATG9L1-pEGFP and labeled with anti-EEA1 (for early endosomes) or anti-RAB11 (for recycling endosomes). The histogram in (C) shows the quantification of the colocalization of mATG9 in EEA1 or RAB11 (Manders' coefficient). Error bars, SEM. ∗∗∗p < 0.001.",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(A) HeLa cells transfected with control, VAMP3 siRNA for 4 days were transfected during the last 20 hr with mStrawberry-ATG16L1 and labeled for mATG9. The correlation between mATG9 and ATG16L1 was quantified (Pearson's coefficient). Error bar, SEM. ∗∗∗p < 0.001.",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(B) HeLa cells were transfected with control or VAMP3 siRNA and then with mStrawberry-ATG16, and 5 min movies were recorded. Homotypic fusion events between mStrawberry-ATG16 vesicles were assessed in control and VAMP3 knockdown cells. Error bar, SEM. NS, not significant.",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(C) In vitro fusion assay of ATG16L1 and mATG9 vesicles. HeLa cells were transfected with control or VAMP3 siRNA for 4 days separately and, on the fourth day, either transfected with mStrawberry-ATG16L1 or ATG9L1-pEGFP. PNS of cells expressing the two constructs were mixed for 1 hr at 37C° and observed by confocal microscopy. Histogram shows the correlation of vesicles carrying ATG16L1 that fuse with vesicles carrying mATG9 (Pearson's coefficient). Error bar, SEM. ∗∗∗p < 0.001. The total number of structures per field (ATG16L1 and ATG9L1) is not significantly different in the control and KD samples (control, 37 ± 3; VAMP3 KD, 45 ± 3; ± SEM; p = 0.106).",
    "ncbi_link": "VAMP3: 9341"
  },
  {
    "caption": "(E) Western blotting and RT-qPCR analysis of Il-17rb, Gpr56, and Scara5 expression in 4T1 cells transduced with Il-17rb, Gpr56, Scara5, or control LacZ shRNA lentivirus respectively.",
    "ncbi_link": "Gpr56: 14766
Il-17rb: 50905
Scara5: 71145"
  },
  {
    "caption": "(F) Soft-agar colony forming activity was examined in lentivirus transduced shIl-17rb, shGpr56, shScara5, or shLacZ 4T1 cells (5x102 cells/well, n = 6 wells per group).",
    "ncbi_link": "Gpr56: 14766
Il-17rb: 50905
Scara5: 71145"
  },
  {
    "caption": "(G) Western blotting analysis was used to detect ectopic expression of Il-17rb in 4T1 cells infected with either lentiviruses carrying Il-17rb cDNA or empty vector.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(H) Soft-agar colony forming activity was examined using control or Il-17rb over-expressing 4T1 cells (5x102 cells/well, n = 6 wells per group).",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(I) Western blotting analysis was used to examine Il-17rb in a representative Il-17rbDel 4T1 clone derived from Il-17rb knocked-out 4T1 cells using a CRISPR/Cas9 system.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(J and K) Tumorigenesis assays were determined in BALB/c mice (n = 3 mice per group) orthotopically injected with 5x102 4T1 cells from WT or Il-17rbDel clone. Tumor mass (J) and weight (K) were measured on day 28. Scale bar: 1 cm.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(L and M) BALB/c mice (n = 3 mice per group) were injected with 5x105 4T1 cells from WT or Il-17rbDel clone via tail-vein. Lung colonization was examined by lung morphology (L) and the numbers of tumor nodule (M) on day 21. Scale bar: 1 cm.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(B and C) Inguinal lymph node-injected BALB/c mice were sacrificed at the indicated week after initial injection. Total cells isolated from inguinal lymph node tissues were transwell co-cultured with 4T1 cells. Inguinal lymph node tissues came from un-injection BALB/c mice as control. After 5-day co-culture, 4T1 cells at lower well were examined in the RT-qPCR (B)analyses of Il-17rb expression. Gapdh was used as an internal control or as a loading control.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(E and F) 4T1-injected BALB/c mice were sacrificed at three weeks post initial injection. Each lymphocyte subsets isolated from inguinal lymph node tissues by FACS sorting were transwell co-cultured with 4T1 cells. After 5-day co-culture, 4T1 cells at lower well were used for the RT-qPCR (E)analyses of Il-17rb expression. Gapdh was used as internal control or as a loading control.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(G) Percentage of CD4+Foxp3+ Tregs of total CD4+ cells in inguinal LN, spleen and peripheral blood of BALB/c mice (n = 3 mice per group) injected with 4T1 (Blue) or γ-irradiated 4T1 (Red) cancer cells was analyzed by FACS.",
    "ncbi_link": "CD4: 12504
Foxp3: 20371"
  },
  {
    "caption": "(H) 4T1 cells co-cultured with the indicated lymphocyte populations isolated from inguinal LN of 4T1 tumor-bearing mice by FACS sorting. After 5-day co-culture, 4T1 cells at lower well were analyzed for Il-17rb expression by RT-qPCR analysis. Gapdh was used as internal control.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": " Figure 6. TGF-β1 secreted from Tregs induces Il-17rb expression of breast cancer cells via Smad2/3/4 signaling. (A) CD4+CD25+ Tregs were isolated from inguinal LN of BALB/c mice injected with 4T1 cells for three weeks, and were transwell cocultured with 4T1 cells in the presence of control IgG or neutralizing antibodies against IL-10 or TGF-β1. After 5-day coculture, 4T1 cells at lower well were analyzed for Il-17rb expression by RT-qPCR analysis. Gapdh was used as internal control. ",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(D) Western blotting analyzed Il-17rb in shLacZ or shTgfbr1 4T1 cells treated with recombinant TGF-β1 for 5 days.",
    "ncbi_link": "Tgfbr1: 21812"
  },
  {
    "caption": "(E) 4T1-injected BALB/c mice were sacrificed at three weeks post initial injection. Total cells isolated from inguinal lymph node tissues were transwell co-cultured with 4T1 cells. After 5-day coculture, soft-agar colony forming activity was determined in co-cultured shLacZ or shTgfbr1 4T1 cells at lower well. (5x102 cells/well, n = 6 wells per group).",
    "ncbi_link": "Tgfbr1: 21812"
  },
  {
    "caption": "(F-H) Western blotting analyzed Il-17rb in shLacZ, shSmad2 (F)4T1 cells treated with recombinant TGF-β1 for 5 days.",
    "ncbi_link": "Smad2: 17126"
  },
  {
    "caption": "(F-H) Western blotting analyzed Il-17rb in shLacZ,shSmad3 (G)4T1 cells treated with recombinant TGF-β1 for 5 days.",
    "ncbi_link": "Smad3: 17127"
  },
  {
    "caption": "(F-H) Western blotting analyzed Il-17rb in shLacZ, shSmad4 (H) 4T1 cells treated with recombinant TGF-β1 for 5 days. ",
    "ncbi_link": "Smad4: 17128"
  },
  {
    "caption": "(I and J) WT 4T1 (I) or Il-17rbDel 4T1 (J) cells were treated with or without recombinant TGF-β1 for 5 days. After treatment, nuclear translocation of NF-κB p65 was assayed by Western blotting in cells treated with recombinant Il-17b for 2 hours. Nuclear Matrix Protein p84 was used as a loading control of nuclear extracts.f triplicate measurement. In (B, C, D, F, G, H, I, and J), the intensity of each band was quantified using the Image J software. Gapdh, α-tubulin, or p84 was used as a loading control. Relative expression (RE) of protein levels in each sample to control 4T1 cells or Il-17rbDel 4T1 clone is indicated.",
    "ncbi_link": "Il-17rb: 50905"
  },
  {
    "caption": "(B) Tumorigenesis assay were determined in NOD/SCID/IL2Rγnull mice orthotopically injected with hBCPT and hBCLN cells. Representative data on day 180 were shown.",
    "ncbi_link": "NOD: 
IL2Rγ: 16186
SCID: 19090"
  },
  {
    "caption": "(G) The correlation of tumor volumes and IL-17RB expression (composite IHC score) in hBCLN cells-injected NOD/SCID/IL2Rγnull mice.",
    "ncbi_link": "IL2Rγ: 16186
NOD: 171584
SCID: 19090"
  },
  {
    "caption": "A) AlexaFluor488-tagged (green) hnRNPA2 LC undergoes LLPS, while AlexaFluor555-tagged (red) TOG D1 does not. However, TOG D1 partitions into hnRNPA2  LC  droplets when mixed at a 1:1 ratio. Conditions: 20 µM indicated protein (~1%  fluorescently tagged), 20 mM MES pH 5.5, 50 mM  NaCl, 150 mM urea. Scale bar: 10 µm.  hnRNPA2 LC control duplicated from Figure 1A as hnRNPF PLD and TOG D1 samples were made concurrently. B) Similar to hnRNPF PLD, AlexaFluor555-tagged TOG D1 does not undergo LLPS at 300 µM or partition into AlexaFluor488-tagged FUS LC droplets with both proteins at 300 µM. Conditions: 300 µM proteins (~1% fluorescently tagged), 20 mM MES pH 5.5 150 mM NaCl, 150 mM  urea. Scale bar: 10 µm. ",
    "ncbi_link": "hnRNPF: 3185"
  },
  {
    "caption": "F) There is no significant difference in number of spots in HRPA-1HsLCWTmScarlet lines with or without Fyn, although there seems to be a trend of reduced spots in HRPA-1HsLCD290VmScarlet lines in animals also expressing  Fyn*; this difference is not statistically significant (ANOVA). N = 12 animals per genotype. G) After exposure to 22 hours  paraquat induced oxidative stress there is no significant difference between HRPA-1HsLCWTmScarlet lines with or without Fyn, although there seems to be a trend of reduced spots in HRPA-1HsLCD290VmScarlet  lines in animals also expressing  Fyn*; this difference is not statistically significant (ANOVA). N = 12 animals per genotype. ",
    "ncbi_link": "mScarlet: 
Fyn: 2534
HRPA-1: 177101"
  },
  {
    "caption": "D) Loss of  C. elegans TDP-43 ortholog,  tdp-1, rescues  glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not  hrpa-1(∆). N=4-12 animals/genotype/trial, significance from  two tailed t-test; tdp-1∆=tdp-1(tgx58). E) Loss of C. elegans TDP-43 ortholog,  tdp-1, rescues glutamatergic tail/phasmid neurodegeneration caused by hrpa-1HsLCD290V after 22 hours paraquat induced oxidative stress, but not hrpa-1(∆). N=4-12 animals/genotype/trial, significance from two tailed t-test; tdp-1∆=tdp-1(ok803). ",
    "ncbi_link": "hrpa-1: 177101
tdp-1: 174436
TDP-43: 174436"
  },
  {
    "caption": "G) Expression of Fyn* in sensory glutamatergic neurons (osm-10 promoter, unc-54 3'UTR) reduces glutamatergic tail/phasmid neuron degeneration in hrpa-1HsLCD290V animals after 22 hours  paraquat induced oxidative stress. N=9-12 animals/genotype/trial, significance from two tailed t-test. H) Expression of an empty Fyn control (Fynempty) in sensory glutamatergic  neurons (osm-10  promoter, unc-54 3'UTR) does not alter glutamatergic phasmid  neuron degeneration in hrpa-1HsLCD290V animals  after 22 hours paraquat induced oxidative stress. N=9-12 animals/genotype/trial. ",
    "ncbi_link": "Fyn: 2534
hrpa-1: 177101
osm-10: 191740"
  },
  {
    "caption": "A Immunostaining for the mitochondrial marker ATPβ in N2a cells expressing mito-QC. Data information: Data are given as mean and SEM, * = p < 0.05, **= p <0.01, **** = p < 0.0001 for simple effects. Scale bar = 5 µm in (A)",
    "ncbi_link": "mito-QC: "
  },
  {
    "caption": "B N2a cells expressing mito-QC and myc-Parkin together with hTau-V5, hP301L-V5 or an empty vector control. Treatment with CCCP (8 µM, 17 h) induces mitophagy in control cells, as indicated by a decrease in the GFP/mCherry fluorescence ratio, but not in hTau or hP301L cells. Deconvolution (Classic Maximum Likelihood Estimation) was applied to images for display only. C Quantification of GFP/mCherry fluorescence intensity per cell. Data were analysed by 2-way ANOVA, showing significant main effects of CCCP treatment, F (1, 314) = 15.66, p < 0.0001, and tau expression, F (2, 314) = 12.26, p < 0.0001, and a significant interaction effect, F (2, 314) = 6.137, p = 0.0024, n = 40-73 cells/group. Data information: Data are given as mean and SEM, * = p < 0.05, **= p <0.01, **** = p < 0.0001 for simple effects. Scale bar = 10 µm",
    "ncbi_link": "mito-QC: 
hTau: 4137"
  },
  {
    "caption": "D Cells expressing mito-QC and myc-Parkin together with hTau-V5, hP301L-V5 or an empty vector control, treated with a mixture of antimycin and oligomycin (AO, 15 µM, 17 h). E Quantification of GFP/mCherry fluorescence intensity per cell. Data were analysed by 2-way ANOVA, showing no significant main effects of AO treatment, F (1, 212) = 0.564, p = 0.4534, or tau expression F (2, 212) = 1.579, p = 0.2087, but a significant interaction effect, F (2, 212) = 9.854, p < 0.0001, n = 16-50 cells/group. Data information: Data are given as mean and SEM, * = p < 0.05, **= p <0.01, **** = p < 0.0001 for simple effects. Scale bar = 10 µm",
    "ncbi_link": "mito-QC: "
  },
  {
    "caption": "B Representative images of N2a cells expressing GFP-Parkin and hTau, hP301L or empty vector (Control) for 24 h, that were then treated with 10 μM CCCP for 4 h. Data information: Data are given as mean and SEM, *= p < 0.05, ***= p < 0.001, ****= p < 0.0001. Scale bar = 10 μm.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "E To assess colocalisation of Parkin clusters and mitochondria at 24 h post-transfection, Pearson correlations between the mean normalised fluorescence intensity of the Parkin clusters and the mitochondrial signal following CCCP treatment were calculated. Control r = 0.616, p = 0.0001; hTau r = 0.217, p = 0.2771; hP301L r = 0.548, p = 0.0014 (n = 27-34 cells/ group). F Pearson correlations between the mean normalised fluorescence intensity of the Parkin clusters and the mitochondrial signal following CCCP treatment at 48 h post-transfection. Control r = 0.434, p = 0.0167; hTau r = 0.128, p = 0.4941; hP301L r = -0.299, p = 0.2794 (n = 15-31 cells/ group). Note the different intensity scales between (E) and (F) reflect different bit depths of the images. Data information: Data are given as mean and SEM, *= p < 0.05, ***= p < 0.001, ****= p < 0.0001. Scale bar = 10 μm.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "A FACS analysis of cells loaded with Rhodamine 123. The geometric mean fluorescence was calculated and expressed as % of the empty vector control. A CCCP-treated cohort was included as a positive control, but not included in the statistical analysis. Data were analysed by one-way ANOVA, F (2, 14) = 0.196, p = 0.8245. B FACS analysis of cells treated with CCCP after 24 h of tau expression. Data were analysed by one-way ANOVA, F (2, 15) = 0.434, p = 0.6555. The DMSO negative control is shown but was not analysed statistically. Data information: Data are given as mean and SEM (n = 5-6 samples/ experimental group from two independent experiments).",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "A Immunostaining for microtubules after transient expression of hTau and hP301L. Data information: Data are given as mean and SEM, ****= p < 0.0001. Scale bar = 10 µm.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "D Immunoblot analysis of acetylated tubulin (Ace-Tubulin) following expression of hTau and hP301L for 24 h (One-way ANOVA, F(2, 9) = 0.0432, p = 0.9579). Data information: Data are given as mean and SEM, ****= p < 0.0001. Scale bar = 10 µm.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "E Immunoblot analysis of tyrosinated tubulin (Tyr-Tubulin) following expression of hTau and hP301L for 24 h (One-way ANOVA, F(2, 9) = 0.0402, p = 0.9608). Data information: Data are given as mean and SEM, ****= p < 0.0001. Scale bar = 10 µm.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "A Co-immunoprecipitations of V5-tagged tau and GFP-Parkin. The V5 tag was used to pull down tau and the membrane was probed for V5 (using an antibody raised in a different species) and GFP. IP = immunoprecipitation, Flow = flow-through lysate following removal of beads. Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "B Maximum projection images of proximity ligation assays (PLAs) for tau and endogenous Parkin in cells expressing hTau-GFP, hP301L-GFP or GFP. Inset = negative control (antibodies to tau and histone H3, which are not known binding partners). C Quantification of PLA signals in maximum projections normalised to the GFP signal. Results were analysed with a Kruskal-Wallis test, χ2 (2) = 27.2, p < 0.0001, followed by Dunn's post hoc analysis to test for differences from the GFP control, n = 17 cells in GFP condition, 14 cells in hTau condition and 27 cells in hP301L condition. Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "F, G PLA for Parkin and ∆Tau, revealing interactions via the projection domain of tau. Data were analysed with a Mann-Whitney test (U = 185, p = 0.9224, n = 21, 18 cells/group for hTau and ∆Tau, respectively). Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "hTau: 4137
Tau: 4137"
  },
  {
    "caption": "H, I PLA for Parkin and the microtubule-binding domain construct (MTBD). Data were analysed with a t-test (t = 5.226, p < 0.0001, n = 16, 17 cells/group for hTau and MTBD, respectively). Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "J, K Cells expressing tau constructs together with GFP-Parkin (24 h) with and without CCCP treatment. Parkin clusters were counted, illustrating that Parkin translocation was impaired by ∆Tau, but not MTBD. Data were analysed with a Kruskal-Wallis test χ2 (2) = 10.4, p = 0.0056, followed by Dunn's post-hoc, n = 67, 42, 53 cells/ group for for hTau, ∆Tau, and MTBD, respectively. Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "L The V5 fluorescence intensity in each cell analysed in (K) (Mann-Whitney test, U = 953, p = 0.2332, n = 42, 53 cells/group for ∆Tau and MTBD, respectively). Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "M Cells were transfected with GFP-Parkin and hTau-V5, hP301L-V5 or an empty vector control, and treated with CCCP. PLAs were performed for tau and Parkin. Notably, at Parkin clusters (arrow), no interactions between tau and Parkin were evident. Data information: Scale bars = 10 μm. Data are given as mean and SEM, ** = p < 0.01, **** = p < 0.0001.",
    "ncbi_link": "hTau: 4137
Parkin: 5071"
  },
  {
    "caption": "C, D Analysis of mitophagy in worms transgenic for mito-Rosella but not tau (WT), that were treated with NaN3 (8 mM, 1 h) or CCCP (15 µM, 2 h). Data were analysed by unpaired t test, NaN3 t = 5.56, p < 0.0001; CCCP t = 3.92 p = 0.0002. Data information: n = 16-25 worms/group for NaN3 and 23-39 worms/groups for CCCP experiments. Data are given as mean and SEM. *** = p < 0.001, **** = p < 0.0001. Scale bar = 10 µm. Images are high-magnification of a small number of mitochondria in the ventral cord",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "E, F Analysis of mitophagy in worms expressing hTau in response to NaN3 treatment (unpaired t test, t = 1.62, p = 0.1126) and CCCP treatment (Mann-Whitney test, U = 113, p = 0.002). Data information: n = 16-25 worms/group for NaN3 and 23-39 worms/groups for CCCP experiments. Data are given as mean and SEM. *** = p < 0.001, **** = p < 0.0001. Scale bar = 10 µm.­­­­ Images are high-magnification of a small number of mitochondria in the ventral cord",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "I Tau expression in worm lysates, as detected using the human tau-specific antibody HT7.",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "(A) MCF10A-eGFP-LC3 cells were left untreated (Control) or treated with 5 μM rapamycin (Rapa), 500 ng/ml TRAIL or 10 ng/ml TNF for 24 h. When indicated, 10 mM 3‐MA or 5 μg/ml TRAIL‐R2 antagonist antibody was added 1 h before the drugs. Representative confocal images (20 μm scale bars) and the percentages of cells with LC3 translocation are shown.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) MCF10A-eGFP-LC3 cells were transfected with the indicated siRNAs for 48 h and analysed by immunoblotting (left), or stimulated with 500 ng/ml TRAIL for 24 h and analysed for LC3 translocation (right).",
    "ncbi_link": "LC3: 81631///84557///440738"
  },
  {
    "caption": "(E) MCF10A-eGFP-LC3 cells transfected with the indicated siRNAs were left untreated 48 h later (Control) or treated with 500 ng/ml TRAIL for 24 h and analysed for the DNA content by flow cytometry. The percentage of apoptotic cells with sub‐G1 DNA content is shown. The values represent mean±s.d. for three (A, D) or four (B, E) independent experiments. *P‐value 0.05, **P‐value 0.01 and ***P‐value 0.001 as compared with control sample (A-left panel and D), with TRAIL‐treated cells without anti‐TRAIL‐R2 (A-right panel) or with TRAIL‐treated cells without siRNA (B, E).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(E) MCF10A-eGFP-LC3 cells transfected with indicated siRNAs for 48 h and incubated for an additional 24 h with or without 500 ng/ml TRAIL were analysed for LC3 translocation (top) and the DNA content (bottom). The values represent mean±s.d. for four independent experiments. *P‐value 0.05 and ***P‐value 0.001 as compared with TRAIL‐treated cells without siRNA. Similar results were obtained in two (A, B and D) or three (C, D) independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) MCF10A-eGFP-LC3 cells were transfected with indicated siRNAs for 48 h and analysed for the indicated mRNAs (top) and proteins (bottom by RT-PCR and immunoblotting, respectively. Similar results were obtained in three independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) MCF10A-eGFP-LC3 cells transfected with indicated siRNAs for 48 h, and left untreated or treated with 500 ng/ml TRAIL for 2 h, 10 μM ionomycin for 24 h or starved for amino acids and glucose for 24 h (starvation) were analysed for P‐ACC and tubulin (loading control) expression by immunoblotting. Similar results were obtained in two independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B, C) The lysates of MCF10A-eGFP-LC3 cells transfected with indicated siRNAs for 48 h and left untreated (−) or treated with 500 ng/ml TRAIL for 2 h were analysed by immunoblotting. (C, lower panel) MCF10A-eGFP-LC3 cells were transfected with indicated siRNAs for 48 h and analysed for the indicated mRNAs by RT-PCR. Similar results were obtained in two independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(D, E) MCF10A-eGFP-LC3 cells were transfected with indicated siRNAs for 48 h, treated as in Figure 3C and analysed for LC3 translocation (left) and sub‐G1 DNA content (right). The values represent mean±s.d. of a minimum of three independent experiments except for the right panel in E (two experiments). *P‐value 0.05 and **P‐value 0.01 as compared with cells treated in a same way, but transfected without siRNA.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B, C) MCF10A-eGFP-LC3 cells left untreated or treated with 500 ng/ml TRAIL, 50 ng/ml TNF or 10 ng/ml IL‐1β for 24 h were analysed for LC3 translocation (B) and the DNA content (C). The values represent mean±s.d. for two independent experiments. **P‐value 0.01 and ***P‐value 0.001 as compared with untreated cells.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) hTERT-RPE1-eGFP-LC3 cells transfected with indicated siRNAs for 48 h were left untreated or treated with 500 ng/ml TRAIL for 24 h and analysed for LC3 translocation (left) and sub‐G1 DNA content (middle) and AMPKα expression (right).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) hTERT-RPE1-eGFP-LC3 cells were transfected with indicated siRNAs for 48 h and analysed for the indicated mRNAs (top). After 48 h, cells were left untreated or treated with 500 ng/ml TRAIL for 2 h, and analysed for P‐ACC and GAPDH (loading control) expression by immunoblotting. Similar results were obtained in two independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(E) Lysates of wild‐type (WT) MEFs and MEFs with an inactive TAK1 knock‐in (TAK1Δ) treated with 500 ng/ml TRAIL were analysed by immunoblotting. Similar results were obtained in two independent experiments.",
    "ncbi_link": "TAK1: 26409"
  },
  {
    "caption": "(F) WT and TAK1Δ MEFs left untreated and treated with 250 or 500 ng/ml TRAIL were analysed for cell death by the LDH release assay. Similar results were obtained in two independent experiments (A, C and E). The values represent mean±s.d. for two (D) or a minimum of three independent experiments (B, F). *P‐value 0.05, **P‐value 0.01 and ***P‐value 0.001 as compared with cells treated in the same way, but transfected without siRNA (B, D) or the wild‐type cells (F).",
    "ncbi_link": "TAK1: 26409"
  },
  {
    "caption": "E. Dual localization of LEO1 to both the fibrillar center and nucleoplasm in GFP-tagged HeLa cells (magenta), also supported by IF antibody staining using HPA040741 (green).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A-B. GNL3 and PES1 are localizing to protein aggregates around the chromosomes in the MKI67 KO cells. A. GNL3 (HPA036743). Median overlapKO = 0.539, median overlapWT = 0.795 (P = 9.34x10-9) and median Pearson correlationKO = -0.335, median Pearson correlationWT = 0.134 (P = 3.58x10-6). B. PES1 (HPA040210). Median overlapKO = 0.516, median overlapWT = 0.755 (P = 1.77x10-13) and median Pearson correlationKO = -0.293, median Pearson correlationWT = 0.129 (P = 4.06x10-13). Data information: Protein of interest is shown in green and DAPI in blue. Scale bar 10 μm. For the colocalization analysis data; biological replicate 1 highlighted in grey and biological replicate 2 in green. Both the overlap and Pearson correlation between DAPI/Protein staining was measured and a two-tailed unpaired Wilcoxon test was used.",
    "ncbi_link": "GNL3: 26354
MKI67: 4288
PES1: 23481"
  },
  {
    "caption": "C. No protein aggregates were observed in MKI67 KO cells for PWP1 (HPA038708), despite being localized to mitotic chromosomes in WT cells. Median overlapKO = 0.523, median overlapWT = 0.861 (P = 1.05x10-13) and median Pearson correlationKO = -0.190, median Pearson correlationWT = 0.515 (P = 8.71x10-15). Data information: Protein of interest is shown in green and DAPI in blue. Scale bar 10 μm. For the colocalization analysis data; biological replicate 1 highlighted in grey and biological replicate 2 in green. Both the overlap and Pearson correlation between DAPI/Protein staining was measured and a two-tailed unpaired Wilcoxon test was used. Box limits mark 1st and 3rd quantile, whiskers the 1.5x interquartile range and center line the median.",
    "ncbi_link": "MKI67: 4288"
  },
  {
    "caption": "D-E. Late recruited proteins do not follow the same recruitment pattern in the MKI67 KO cells compared to WT HeLa cells. White arrows indicate where protein aggregates can be seen. D. DENND4A (HPA065343). Median overlapKO = 0.671, median overlapWT = 0.803 (P = 1.02x10-4) and median Pearson correlationKO = -0.224, median Pearson correlationWT = 0.236 (P = 1.91x10-5). E. NOL12 (HPA003547). Median overlapKO = 0.468, median overlapWT = 0.820 (P = 1.01x10-17) and median Pearson correlationKO = -0.318, median Pearson correlationWT = 0.381 (P = 1.81x10-10). White arrow indicates metaphase cell. Data information: Protein of interest is shown in green and DAPI in blue. Scale bar 10 μm. For the colocalization analysis data; biological replicate 1 highlighted in grey and biological replicate 2 in green. Both the overlap and Pearson correlation between DAPI/Protein staining was measured and a two-tailed unpaired Wilcoxon test was used. Box limits mark 1st and 3rd quantile, whiskers the 1.5x interquartile range and center line the median.",
    "ncbi_link": "MKI67: 4288"
  },
  {
    "caption": "F, Chow fed hIGFREO had similar body mass to WT, however, hIGFREO did not gain as much weight as WT after 8 weeks of HFD (n=6-10 mice per group).",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "G, Representative images of difference in fat and water distribution shown by magnetic resonance (MR) imaging in hIGFREO and WT. Scale bar = 1cm.",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "hIGFREO glucose intolerance measured by glucose tolerance test (n=5-7 mice per group).",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "G, H, Percentage change in plasma levels of triglycerides after an olive oil oral gavage was reduced over the 3hr period post gavage in hIGFREO compared to WT and shown as area under the curve (n=10-12 mice per group).",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "hIGFREO , food consumption using indirect calorimeter assessment after HFD compared to wildtype littermates (WT) after HFD. (n=4 per genotype).",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "Faith's phylogenetic diversity (PD) was used to measure the fecal microbial diversity and demonstrates a significant difference between human IGF-1R endothelial overexpressing mice (hIGFREO) mice and wildtype littermates (WT) mice after high fat diet feeding (n=4-5 mice per group). Chao-1 analysis was used to measure the fecal microbial diversity and abundance and demonstrates a significant difference between hIGFREO and WT (n=4-5 mice per group).",
    "ncbi_link": "IGF-1R: 3480
IGFR: 3480"
  },
  {
    "caption": "B, Bi, human IGF-1R endothelial overexpressing mice (hIGFREO) had comparable weight gain as wildtype littermates (WT) after 8 weeks of HFD + antibiotics (ABs) when compared to WT. Bii, both hIGFREO and WT gained significant weight compared to chow fed mice (n=7=9 mice per group).",
    "ncbi_link": "IGF-1R: 3480
IGFR: 3480"
  },
  {
    "caption": "D, E, There was no difference in hIGFREO and WT glucose tolerance (as measured by glucose tolerance test and area under the curve (AUC)) (n=7-9 mice per group).",
    "ncbi_link": "IGFR: 3480"
  },
  {
    "caption": "Confocal z-projections of the indicated genotypes and age, labeled with membrane bound GFP (mCD8-GFP; CD8) driven by the γ-specific Gal4 driver GMR71G10-Gal4 (γ-Gal4). While γ-axons of control flies project through the entire lobe (C is the RNAi control; n=12/12, E; is the tsCRISPR control; n=14/14), knockdown of dpr12 by RNAi (D; n=12/12) or knockout by tsCRISPR (F; n=14/14) resulted in short axons. At L3, γ-axons in dpr12∆50-81 homozygotus mutant animals (K; n=20/20) resemble WT γ-axons (G; n=20/20). At 48hr APF, γ-axons normally re-extend to form the adult lobe (H; n=12/12). dpr12∆50-81 γ-axons (L; n=14/14) fail to extend to the end of the lobe. This defect persists to adult (I; n=11/11 vs. M; n=18/18). Expressing a UAS-Dpr12 transgene within γ-KCs in dpr12∆50-81 homozygote mutant animals rescued the axon regrowth defect (N; n=23/24, J; n=14/14). The adult γ-lobe and α/β lobes are outlined in (C, D) in yellow and orange, respectively, for clarity. Asterisks demarcate the distal part of the lobe. Green and white indicate mCD8-GFP. Magenta represents FasII staining. Scale bar is 20 µm.",
    "ncbi_link": "dpr12: 50320
Dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "Confocal z-projections of MARCM neuroblast (NB, A-F) and single-cell (SC, G-L) clones labeled with membrane bound GFP (mCD8-GFP; CD8) driven by the γ specific Gal4 driver GMR71G10-Gal4 (γ-Gal4). At L3, NB and SC clones expressing dpr12 RNAi are similar to equivalent WT clones (A; n=20/20, D; n=15/15, G; n=15/15 and J; n=17/17). At 48hr APF and adult stage, WT NB (B; n=15/15, C; n=10/10) and SC (H; n=16/16, I; n=13/13) clones extend their axons to form the full adult lobe. In contrast, clones expressing dpr12 RNAi (E; n=14/14, F; n=22/2, K; n=18/24, L; n=19/27) fail to extend their axons to the distal part of the medial lobe (asterisks). I' and L' are traces of multiple single-cell clones depicting each cell in a different color.",
    "ncbi_link": "dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "Confocal z-projections of brains expressing MiMIC mediated Dpr12GFSTF (Dpr12-GFP; A-D) and DIP-δGFSTF (DIP-δ-GFP; E-H) fusion proteins at the indicated time points. See Figures EV 1 and 4 for more details on the fusion protein structure. (A-D) Dpr12-GFP is localized to the distal part of the γ-lobe at L3 (A; n=10/10), 48hr APF (C; n=12/12) and the adult stage (D; n=20/20), where it colocalizes with the γ4>γ1γ2 MBON (γ4; labeled by GMR18H09-Gal4 driving the expression of CD4-tdT). At 24hr APF (B; n=10/10), Dpr12-GFP appears diffuse. (E-H) DIP-δ-GFP is localized to the distal part of the γ-lobe throughout development: L3 (E; n=16/16), 24hr APF (F; n=10/10), 48hr APF (G; n=12/12) and adult (H; n=24/24). At the adult stage, DIP-δ-GFP is colocalized with the γ4>γ1γ2 MBON (γ4).",
    "ncbi_link": "GFP: 
DIP-δ: 5740816
Dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "Confocal z-projections DIP-δ hetero- and homozygous brains in which γ-KCs were labeled by expressing membrane bound tandem tomato (mtdT-HA) driven by the γ specific QF2 driver R71G10-QF2 (γ-QF2). Larval (L3) γ-axons grow normally in DIP-δT2A-Gal4 heterozygotes (A; n=16/16) and homozygotes (E; n=24/24). In contrast, at 48hr APF and adult, γ-axons within DIP-δT2A-Gal4 homozygotes do not enter the distal part of the lobe (asterisks; F; n=8/8, G; n=20/20), while they grow normally in heterozygotes (B; n=12/12, C; n=12/12). Overexpression of a DIP-δ transgene driven by the Gal4 activity of DIP-δT2A-Gal4 (see also Figure S4) does not affect normal growth (D; n=10/10) and rescues mutant phenotypes (H; n=20/20). Note that while the R71G10 driver is consistently expressed in γ-KCs, it is also expressed in α/β-KCs in a stochastic manner. The adult γ-lobe and α/β lobes are outlined in C-D in yellow and orange, respectively, for clarity.",
    "ncbi_link": "DIP-δ: 5740816
Gal4: 855828
QF2: 3875756
γ-QF2: 3875756"
  },
  {
    "caption": "Confocal z-projections of brains expressing DIP-δ-RNAi driven by the indicated Gal4. γ-KCs are labeled by mtdT-HA driven by R71G10-QF2 (γ-QF2). Expression of DIP-δ-RNAi in all glia (Repo-Gal4, J; n=28/28) or all KCs (OK107-Gal4, K; n=12/12) did not affect γ-neuron regrowth. In contrast, expression of DIP-δ-RNAi in all postmitotic neurons (C155-Gal4, L; n=9/12) or DIP-δ expressing neurons (DIP-δT2A-Gal4, M; n=21/22) induced a defect in γ4/5 innervation by γ-axons.",
    "ncbi_link": "DIP-δ: 5740816
C155: 31000
OK107: 43812
Gal4: 855828
QF2: 3875756
γ-QF2: 3875756
Repo: 47285"
  },
  {
    "caption": "(A-D) Confocal z-projections of brains expressing DIP-δGFSTF (DIP-δ-GFP) together with the indicated Gal4s and transgenes. Expressing diphtheria toxin (DTi) and the membrane bound RFP (mCD8-RFP; CD8) driven by the γ4>γ1γ2 MBON driver MB294B-Gal4 (MBONγ4>γ1γ2-Gal4) did not affect DIP-δ-GFP expression (A, n=16/16; B, n=14/14). In contrast, similar expression of DTi and membrane bound Tomato (CD4-tdT; CD4) in PAM-DANs (using the GMR58E02-Gal4; PAM-DAN-Gal4) abolished the normal DIP-δ-GFP expression in the γ4/5 zone (compare D, n=18/18, to C, n=16/16) and within the PAM-DAN cell bodies (compare D' to C'). Magenta is CD8-RFP (A-B), CD4-mtdT (C-D). Green is GFP, grayscale depict individual channels as labeled. Scale bar is 20 µm. Yellow dashed line demarcates the γ-lobe based on FasII staining (not shown).",
    "ncbi_link": "DIP-δ: 5740816
Gal4: 855828"
  },
  {
    "caption": "(E-G) Confocal z-projections of MARCM clones labeled by DIP-δT2A-Gal4 (DIP-δ Gal4) driving the expression of membrane bound GFP (mCD8-GFP; CD8) and heat shocked at 24hr after egg laying. Clones innervate the γ4/5 zones at 24hr APF (E; n=8), 48hr APF (F; n=8) and adult (G; n=16). Clones become tyrosine hydroxylase (TH) positive only at 48hr APF onwards (F,G). Magenta is FasII, green is mCD8-GFP, cyan is TH antibody staining, grayscale single channels are shown as indicated. White dashed line demarcates the γ-lobe. Scale bar is 20 µm.",
    "ncbi_link": "DIP-δ: 5740816
Gal4: 855828"
  },
  {
    "caption": "(A-J) Confocal z-projections of brains expressing MiMIC mediated Dpr12GFSTF (Dpr12-GFP) and DIP-δGFSTF (DIP-δ-GFP) fusion proteins of the indicated genotypes and time points. (A-D) Dpr12-GFP expression is diffuse in DIP-δT2A-Gal4 homozygotes mutant brains at L3 (A; n=20/20), 24hr APF (B; n=14/14), 48hr APF (C; n=28/28) and adult (D; n=26/26). (E-H) DIP-δ-GFP expression in dpr12∆50-81 homozygotes mutant brains remains localized to the distal part of the γ-lobe at L3 (E; n=16/16), 24hr APF (F; n=16/16), and 48hr APF (G; n=10/10) but cannot be identified in adult brains (H; n=16/16). (I-J) Dpr12-GFP expression in WT animals (I, n=8/8) or in those ectopically expressing DIP-δ in PAM-DANs that innervate the γ3 zone (J, n=14/14) driven by MB441B-Gal4 (PAM-DAN-γ3-Gal4). DIP-δ expression in PAM-DAN-γ3 resulted in Dpr12-GFP localization within the γ3 zone (arrow), in addition to its normal γ4/γ5 localization.",
    "ncbi_link": "DIP-δ: 5740816
dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "Confocal z-projections of dpr12∆50-81 heterozygous (A, n=15; C, n=10; E, n=10) and homozygous brains (B, n=8; D, n=18; F, n=24) expressing mCD8-GFP (CD8) driven by (E, F) R18H09-Gal4 (MBONγ4>γ1γ2 -Gal4). The greyscale channels are sub-z-projections comprised of slices restricted to the γ-lobe region. White dashed line demarcates the γ-lobe. Bottom: Cartoons schematizing MB lobe structure and innervation by specific PAM-DANs or MBON.",
    "ncbi_link": "dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "Single confocal slices of WT (G, n=5/5) and dpr12∆50-81 homozygous brains (H, n=5/5) stained with anti-Brp. Dashed lines demarcate neuropil boundaries, schematic shown below. Cre, crepine, a neuropil that surrounds the medial MB lobes; AL, antenna lobe.",
    "ncbi_link": "dpr12: 50320"
  },
  {
    "caption": "(C, D) Confocal z-projections of adult DIP-δT2A-Gal4/1-119 trans-heterozygous mutant (D) or DIP-δ1-119/+ heterozygous (C) brains, which express MiMIC mediated Dpr12GFSTF (Dpr12-GFP; green), in which DIP-δ-Gal4 either drives expression or UAS-DIP-α (D) or not (C). Grayscale panels represent single channels, as indicated. The γ-lobe is outlined in white.",
    "ncbi_link": "DIP-α: 31322
DIP-δ: 5740816
Gal4: 855828"
  },
  {
    "caption": "(E, F) Confocal z-projections of adult dpr12Δ50-81 homozygous mutant brains, in which DIP-δ-Gal4 drives expression of either UAS-mtdT (E) or UAS-DIP-α-T2A-tdT (F; expected to induce expression of DIP-α as well as tdT encoded by a polycistronic message). In orange are longitudinal sections across the γ-lobe at the indicated location. The γ-lobe is outlined in white, as determined by FasII staining (grey in E'-F'). Cyan is tdT within DIP-δ+ cells. Grey boxes below the images describe the relevant components within PAM-DANs and γ-KCs.",
    "ncbi_link": "DIP-α: 31322
dpr12: 50320
Gal4: 855828"
  },
  {
    "caption": "(A) WT and atg1Δ cells grown in YEPD medium were transferred to SD-N or SD-N +50 mM MES-KOH (pH 6.2) medium for 120 hours, and dead cells stained by phloxine B were observed by fluorescent microscopy. Scale bar, 25 µm.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(B-C) WT and atg1Δ cells grown nitrogen starved as (A) for the indicated times. Cell viability (B) and medium pH (C) were examined by phloxine B staining and pH meter, respectively. These data represent the average of three independent experiments and bars indicate standard deviations.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(A) WT and atg1Δ cells grown in YEPD medium were transferred to SD-N +50 mM MES-KOH (pH 6.2). After 120 hours, cultures were diluted 5.0×105 fold and plated onto YEPD agar. The plates were incubated at 30°C for four days. Insets indicate the plate overlaid with TTC agar to examine the respiratory competency of formed colonies.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(B) WT, and atg1Δ cells were nitrogen-starved as (A). Cell viability and respiratory competency was determined by phloxine B staining and TTC overlay technique as (A), respectively. The black and gray areas indicate the percentage of viable cells that are respiratory competent or respiratory deficient, respectively.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(C) WT, atg1Δ, atg2Δ, atg7Δ, atg11Δ, atg15Δ, and atg32Δ cells were nitrogen-starved as (A). Cell viability and respiratory competency was determined by phloxine B staining and TTC overlay technique as (A), respectively. The black and gray areas indicate the percentage of viable cells that are respiratory competent or respiratory deficient, respectively. These data represent the average of three independent experiments and bars indicate standard deviations.",
    "ncbi_link": "atg1: 852695
atg11: 856162
atg15: 850432
atg2: 855479
atg32: 854660
atg7: 856576"
  },
  {
    "caption": "(A) WT and atg1Δ cells expressing mitochondria targeted mCherry cultured in SD-N +50 mM MES-KOH (pH 6.2) medium for 120 hours were observed by fluorescent microscopy. Mitochondrial DNA was stained with SYBR green I, and mitochondria were visualized by mitochondria targeted mCherry. Scale bar, 2 µm.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(B-C) WT and atg1Δ cells were transferred to SD-N +50 mM MES-KOH (pH 6.2) medium for the indicated time. ROS accumulation was detected by DHE staining (B). Each photo contains about 200 cells. Scale bar, 20 µm. (C) shows quantification of ROS accumulated cells (n>200 cells).",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(D) WT and atg1Δ cells were transferred to SD-N +50 mM MES-KOH (pH 6.2) with 10 mM NAC for the indicated time. Cell viability was determined by phloxine B staining. Cells from these cultures were plated on YEPD agar and overlaid with TTC agar to examine respiratory competency. The black and gray areas indicate the percentage of viable cells that are respiratory competent or respiratory deficient, respectively. These data represent the average of three independent experiments and bars indicate standard deviations",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(A) WT and atg1Δ cells were transferred to SD-N +50 mM MES-KOH (pH 6.2) medium for the indicated time. Lysates were prepared using the alkaline-trichloroacetic acid method and subjected to immunoprecipitation with anti-Cox2, anti-Cox4, anti-Tim17 and anti-Pgk1. Pgk1 was used as loading control.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(B) WT and atg1Δ cells expressing Cta1-3×FLAG or Ctt1-3×FLAG were nitrogen-starved as in (A) for the indicated time. Cell lysates were prepared as (A) and subjected to immune precipitation with anti-FLAG and anti-Pgk1. Pgk1 was used as loading control.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(A) WT and atg1Δ cells were transferred to non-buffered SD-N medium for the indicated time. Cell viability was determined by phloxine B staining. Nitrogen-starved cells were plated onto YEPD agar and overlaid with TTC agar to examine the respiratory competency of formed colonies. The black and gray areas indicate the percentage of viable cells that are respiratory competent or respiratory deficient, respectively.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(B) WT, atg1Δ, rho0, and rho0 atg1Δ cells grown in YEPD medium were transferred to SD-N with or without 10 mM NAC for the indicated time. In the presence of NAC, medium pH was adjusted by using KOH. Cell viability and medium pH were examined by phloxine B staining and pH meter, respectively. These data represent the average of three independent experiments and bars indicate standard deviations.",
    "ncbi_link": "rho: 
atg1: 852695"
  },
  {
    "caption": "A Atf7ip KO cells show increased expression of SETDB1-regulated ERVs and the provirus reporter, MSCV-GFP as evidenced by RT-qPCR analysis. RNA expression was normalized to Hprt expression and is shown relative to the level in WT cells. Data are mean ± SD; n=3, technical replicates.",
    "ncbi_link": "GFP: 
Atf7ip: 54343
Hprt: 15452
SETDB1: 84505"
  },
  {
    "caption": "B Atf7ip KO mESCs (TT#2-12) show decreased H3K9me3 at the LTR of the SETDB1-regulated reporter and the ERVs, as evidenced by Native ChIP followed by qPCR analysis. Gapdh was used as a negative control. Data are mean ± SEM; n=5, independent experiments. *P < 0.05 and **P < 0.01 by paired t-test.",
    "ncbi_link": "Atf7ip: 54343
Gapdh: 14433
H3: 15078
SETDB1: 84505"
  },
  {
    "caption": "C SETDB1 cellular amount is mostly maintained in Atf7ip KO mESCs. Endogenous SETDB1-ATF7IP interaction is validated by anti-ATF7IP antibody co-IP experiment with anti-ATF7IP antibody.",
    "ncbi_link": "Atf7ip: 54343"
  },
  {
    "caption": "A IF analysis shows preferential cytoplasmic localization of SETDB1 in Atf7ip KO mESCs. Representative projected images are shown, and the quantitative analyses are shown in B-D. Scale bar: 10 µm. B SETDB1 signal in the nucleus that was determined by DAPI staining was calculated. The mean from three independent experiments is shown as a bar-graph with jittered points indicating the average % intensity of each experiment. Over 100 cells were analysed per sample per experiment. ***P < 0.001 by unpaired Student's t-test. C, D SETDB1 foci in the nucleus that was determined by DAPI staining were calculated. Violin plot for SETDB1's foci numbers from all the cells analysed in three independent experiments is shown in c. The mean from the three independent experiments is shown as a bar with jittered points indicating the average number of each experiment in D. Over 100 cells were analysed per sample per experiment. *P < 0.05 by unpaired Student's t-test. ",
    "ncbi_link": "Atf7ip: 54343"
  },
  {
    "caption": "E, IF analysis shows preferential cytoplasmic localization of SETDB1 in Atf7ip KO mESCs. Representative projected images are shown. Arrows indicate the region used for line-plot analysis. Cells were treated with 10 ng/mL LMB or mock for 5 h before analysis. Scale bar: 10 µm. F The line-plot analysis for E. Relative intensities of SETDB1 signal were measured by Image J. G The quantitative analysis for E is shown. SETDB1 signal in the nucleus that was determined by DAPI staining was calculated. The mean from three independent experiments is shown as a bar-graph with jittered points indicating the average % intensity of each experiment. Over 100 cells were analysed per sample per experiment. NS: P > 0.05, **P < 0.01 versus "Mock, WT" group by Dunnett's test. ",
    "ncbi_link": "Atf7ip: 54343"
  },
  {
    "caption": "A ATF7IP KO HEK293T cells shows endogenous SETDB1 cytoplasmic localization phenotype. Endogenous SETDB1 in HEK293T cells shows cytoplasm+nuclear localization profile. Scale bar: 10 µm.",
    "ncbi_link": "ATF7IP: 55729"
  },
  {
    "caption": "B Over-production of exogenous mouse SETDB1 induces endogenous SETDB1 nuclear localization in both WT and ATF7IP KO HEK293T cells. The representative data of two independent experiments is shown. Scale bar: 10 µm.",
    "ncbi_link": "ATF7IP: 55729"
  },
  {
    "caption": "C LMB treatment enhances SETDB1 nuclear accumulation in WT HEK293T cells, but no significant impact for ATF7IP KO HEK293T cells. Cells were treated with 10ng/ml of LMB for 5 h and then analysed with immunofluorescent staining. The representative data of three independent experiments is shown. Scale bar: 10 µm. D SETDB1 signal in the nucleus shown in C was calculated. The mean from three independent experiments is shown as a bar-graph ± SEM; n=3. Over 50 cells were analysed per sample per experiment. **P < 0.01 by Student's t-test (two-sided test). ",
    "ncbi_link": "ATF7IP: 55729"
  },
  {
    "caption": "E 5 h of proteasome inhibitor bortezomib treatment do not have much impact on SETDB1 relative nuclear accumulation in ATF7IP KO HEK293T cells. The representative data of three independent experiments is shown. Scale bar: 10 µm. F SETDB1 signal in the nucleus shown in E was calculated. The mean from three independent experiments is shown as a bar-graph ± SEM; n=3. Over 50 cells were analysed per sample per experiment. Statistics comparison was only shown between without and with drug treatment in WT and ATF7IP KO cells. *P < 0.05 and **P < 0.01 by Dunnett's method. ",
    "ncbi_link": "ATF7IP: 55729"
  },
  {
    "caption": "A HEK293T cells were transfected with V5-SETDB1 and either empty or 3xF-ATF7IP expressing vector. Over 50 transfected cells analysed per sample were analyzed. The representative data of two independent experiments is shown. Scale bar: 10 µm.",
    "ncbi_link": "V5: 
ATF7IP: 54343
SETDB1: 84505"
  },
  {
    "caption": "B HEK293T cells were transfected with V5-SETDB1 d1 mutant and either empty or 3xF-ATF7IP expressing vector. Over 50 transfected cells per sample were analysed. The representative data of two independent experiments was shown. Scale bar: 10 µm. The yellow arrowheads indicate the cells that show nuclear (and cytoplasmic)-localization of introduced exogenous mSETDB1.",
    "ncbi_link": "V5: 
ATF7IP: 54343
SETDB1: 84505"
  },
  {
    "caption": "A Co-transfection with ATF7IP augments the K885 ubiquitination of SETDB1. HEK293T cells were transfected After the transfection, V5-SETDB1 was immune-purified with anti-V5 antibody and used for WB analysis.",
    "ncbi_link": "ATF7IP: 54343"
  },
  {
    "caption": "B ATF7IP regulates the ubiquitination of SETDB1 in mESCs. Endogenous SETDB1 was immune-purified from WT or Atf7ip KO mESCs cells and used for WB analysis.",
    "ncbi_link": "Atf7ip: 54343
ATF7IP: 54343"
  },
  {
    "caption": "C LMB treatment increased the relative intensity of the upper ubiquitinated upper band of SETDB1 in Atf7ip KO mESCs. Cells were treated with 10 ng/mL LMB or mock for 5 h before analysis.",
    "ncbi_link": "Atf7ip: 54343"
  },
  {
    "caption": "D HEK293T cells were transfected with either 3xF- or 3xF-NLS-SETDB1. Over 50 transfected cells per sample were analysed. The representative data of two independent experiments is shown. Scale bar: 10 µm.",
    "ncbi_link": "SETDB1: 84505"
  },
  {
    "caption": "E Nuclear localization itself promotes the ubiquitination of SETDB1. HEK293T cells were transfected with 3xFLAG- or 3xFLAG-NLS-SETDB1. After FLAG-IP, the purified SETDB1s were analyzed by WB.",
    "ncbi_link": "FLAG: 
SETDB1: 84505"
  },
  {
    "caption": "F, G IF analysis was performed with Atf7ip KO mESCs stably expressing 3xF- or 3xF-NLS-SETDB1. Representative images are shown in F, and the quantitative analysis is shown in G. Scale bar: 10 µm. Addition of NLS increases nuclear localization of SETDB1 in Atf7ip KO mESCs. The mean from three independent experiments is shown as a bar-graph with jittered points indicating the average % intensity of each experiment. Over 50 cells were analysed per sample per experiment. ***P < 0.001 by unpaired Student's t-test.",
    "ncbi_link": "Atf7ip: 54343
SETDB1: 84505"
  },
  {
    "caption": "H Nuclear localization promotes the ubiquitination of SETDB1 in Atf7ip KO mESCs. Atf7ip KO mESCs expressing 3xF- or 3xF-NLS-SETDB were used for FLAG-IP, and the purified SETDB1s were analyzed by WB.",
    "ncbi_link": "Atf7ip: 54343
SETDB: 84505"
  },
  {
    "caption": "F, G (F) PCR  for Cγ1-Cre and wildtype Cγ1 alleles and (G), wildtype, floxed or excised Blimp1 alleles in DNA from wildtype (wt) control C57bl/6J cells and purified  T-cells or CD45.2+ cells from  mouse with  lymphoma (T1, T2). PCR  data were confirmed in at least 3 independent tests. Lad. = ladder.",
    "ncbi_link": "Cre: 2777477
Cγ1: 18803
Blimp1: 12142"
  },
  {
    "caption": "B PIPKIγi5 specifically interacts with LAPTM4B, but not LAPTM4A or LAPTM5. Top: schematic diagram of all three LAPTM members. Bottom: each Flag‐tagged LAPTM protein was immunoprecipitated from HEK293 cells cotransfected with Myc‐tagged PIPKIγi5 and empty vector or Flag‐tagged LAPTM, and the co‐immunoprecipitatedPIPKIγi5 was examined by immunoblotting.",
    "ncbi_link": "LAPTM4A: 9741
LAPTM4B: 55353
LAPTM5: 7805"
  },
  {
    "caption": "D Kinase activity of PIPKIγi5 is required for LAPTM4B association. HEK293 cells expressing LAPTM4B and wild‐type (WT) or kinase‐dead (KD) PIPKIγi5 were starved overnight, stimulated or not with 100 ng/ml EGF for 15 min, and harvested for immunoprecipitation with anti‐myc. The co‐immunoprecipitatedLAPTM4B was detected by immunoblotting.",
    "ncbi_link": "PIPKIγi5: 23396"
  },
  {
    "caption": "E Control or LAPTM4B siRNA‐transfected MDA‐MB‐231 cells were starved, pulsed with 25 ng/ml Alexa‐555‐EGF for 3 min, washed, and chased for indicated time periods followed by fixation, DAPI staining, and fluorescence microscopy. Scale bar: 10 μm.F Quantification of the relative amounts of Alexa‐555‐EGF internalized in the indicated conditions (mean + SD, n = 3).G Quantification of the Alexa‐555‐EGF degradation in control and LAPTM4B knockdown cells in (E) (mean ± SD, n = 3).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "H Control or LAPTM4B‐overexpressing MDA‐MB‐231 cells were starved and then stimulated with 100 ng/ml EGF for 1-4 h. EGFR degradation and signaling were analyzed by Western blot. Specific antibodies recognizing pEGFR (Y1068) and pAKT (S473) were used.I-K Quantification for the levels of EGFR (I) and pEGFR (J) normalized to actin and pAKT (K) normalized to AKT in control or LAPTM4B‐overexpressing cells (mean ± SD, n = 3).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "A-D Control or LAPTM4B siRNA‐transfected MDA‐MB‐231 cells were starved, pretreated or not with chloroquine for 2 h, stimulated with 100 ng/ml EGF for 15 min, washed, and chased for indicated time periods before fixation for costaining of EGFR (red) with EEA1 (A, green) or LAMP1 (C, green). Quantification of the average percentages of EGFR signals colocalized with EEA1 (B) and LAMP1 (D) at indicated time points; mean + SD; n = 3; *P 0.05, **P 0.01, ***P 0.001, one‐tailed t‐test.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "C Control or LAPTM4B knockdown MDA‐MB‐231 cells were starved overnight, cell surface EGFR was labeled with immuno‐gold on ice. Cells were then stimulated with EGF for 1 h at 37°C and fixed for the EM study. Scale bar, 200 nm. See Materials and Methods for details.D Relative amounts of immuno‐gold‐labeled EGFR in the MVE lumen versus MVE limiting membrane were quantified. Over 80 endosomes for each siRNA treatment from three independent experiments were used for quantification (mean + SD; ***P 0.001, one‐tailed t‐test).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "A Co‐immunoprecipitation (co‐IP) of full‐length or N‐terminus‐deleted LAPTM4B with PIPKIγi5 in HEK293 cells.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "C Co‐IP of full‐length or N‐terminal deletion mutants of LAPTM4B with PIPKIγi5 in HEK293 cells. ∆25: amino acids 1-25 deleted.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "E Coomassie Brilliant Blue staining of purified wild‐type and mutated LAPTM4B N‐termini.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "F Purified LAPTM4B N‐termini from (E) were used in PIP strips assay. LPA, lysophosphatidic acid; LPC, lysophosphocholine; PE, phosphatidylethanolamine; PC, phosphatidylcholine; S1P, sphingosine 1‐phosphate; PI3,4,5P3, PtdIns(3,4,5)P3, phosphatidylinositol (3,4,5)‐trisphosphate; PA, phosphatidic acid; PS, phosphatidylserine.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "GST pull‐down assay of wild‐type or 6RQ mutant of LAPTM4B N‐termini with PIPKIγi5 C‐terminus.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "I Top: GSTpull‐down assay of LAPTM4B N‐terminus and PIPKIγi5 C‐terminus with increased concentration of PtdIns(4,5)P2 addition. Bottom: Quantification of the relative amounts of PIPKIγi5 C‐terminus bound to LAPTM4B N‐terminus in top panel (mean ± SD; n = 4).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "K Top: GSTpull‐down assay of LAPTM4B N‐terminus and PIPKIγi5 C‐terminus with 0.5 μM addition of different phosphoinositides. Bottom: Quantification of the relative amounts of PIPKIγi5 C‐terminus bound to LAPTM4B N‐terminus in top panel (mean + SD; n = 4).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "L Top: GSTpull‐down assay of wild‐type or 6RQ mutant of LAPTM4B N‐terminus and PIPKIγi5 C‐terminus with 0.5 μM addition of PtdIns(4,5)P2. Bottom: Quantification of the relative amounts of PIPKIγi5 C‐terminus bound to LAPTM4B N‐terminus in top panel (mean + SD; n = 4).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "A Control or LAPTM4B knockdown MDA‐MB‐231 cells were starved and stimulated with 100 ng/ml EGF for 30 min, and whole‐cell lysates were subject to co‐immunoprecipitation (co‐IP) assay.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "G The effects of LAPTM4B‐6RQ mutant overexpression on EGF‐stimulated EGFR degradation and signaling. Flag‐LAPTM4B‐WT or 6RQ mutant overexpression was accomplished by lentivirus‐mediated infection approach. Cells with low levels of expression were selected as polyclonal pools for comparison. Control or overexpressing cells were starved and stimulated with 100 ng/ml EGF for indicated time periods and whole‐cell lysates were analyzed by Western blot.",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "J The effects of LAPTM4B‐2PA mutant overexpression on EGF‐stimulated EGFR degradation and signaling. Overexpression of Flag‐LAPTM4B‐WT or 2PA mutant overexpression was accomplished by lentivirus‐mediated infection approach. Cells with high expression of Flag‐LAPTM4B were selected as polyclonal pools for comparison. Cells were starved and stimulated with 100 ng/ml EGF for the indicated time periods, and whole‐cell lysates were analyzed by Western blot.K Quantification of EGFR degradation from Western blot in (J) (mean ± SD; n = 3).",
    "ncbi_link": "LAPTM4B: 55353"
  },
  {
    "caption": "D PIPKIγi5 promotes SNX5 association with LAPTM4B. HEK293 cells cotransfected with indicated proteins were harvested for co‐IP to assay the interaction between Myc‐SNX5 and Flag‐LAPTM4B.",
    "ncbi_link": "LAPTM4B: 55353
SNX5: 27131"
  },
  {
    "caption": " Similarity plot of the near full-length genome sequence (A) and S gene sequence (B) of Pangolin-CoV to sequences of 2019-nCoV_WIV02, Bat-CoV RaTG13, Bat-CoV ZC45 and Bat-CoV ZXC21. While Pangolin-CoV has a high sequence identity to 2019-nCoV and Bat-CoV-RaTG13 in most regions of the S gene, it is more similar to Bat SARSr-CoV ZXC21 and Bat SARSr-CoV ZC45 at the 5′ end (B). More importantly, Pangolin-CoV is highly similar to 2019-nCoV in the functional RBD region of the S protein, with only one amino difference (insert in B). Because of the presence of genetic recombination, there is a discrepancy in cluster formation among the outcomes of phylogenetic analyses of different regions of the S gene (C). ",
    "ncbi_link": "RBD: 
S gene: "
  },
  {
    "caption": "Scatterplot depicting the positive correlation between TP53 expression values and Alu RNA processing ratio in AD patients (r=0.65, p < 0.001). Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Scatterplot depicting no correlation between TP53 expression values and full length Alu RNA levels in AD patients (r=0.06, no correlation, ns=non-significant). Statistical test as in subfigure 5C.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Expression levels of full length Alu RNA (RT-qPCR) in the Alu RNA KD experiment. Statistical significance (p value threshold 0.05) for the comparison between anti-Alu LNA treated samples (anti-Alu) and samples treated with a scramble control LNA (ctrl) with p=0.049 and n=3, unpaired non-directional t-test. Error bars represent standard deviation from the mean. Expression levels of P53 (RT-qPCR) in the Alu RNA KD experiment. Statistical significance (p value threshold 0.05) for levels in anti-Alu LNA treated samples (anti-Alu) greater than samples treated with a scramble control LNA (ctrl) with p=0.046 and n=3, unpaired directional t-test. Error bars represent standard deviation from the mean.",
    "ncbi_link": "P53: 7157"
  },
  {
    "caption": "Scatterplot depicting the positive correlation between HSF1 mRNA expression values and Alu RNA processing ratio in MAP AD patients (r=0.72, p<0.001). Statistical test is based on Pearson's product moment correlation coefficient and follows a t distribution using the cor.test function in R package stats. Scatterplot depicting lack of correlation between HSF1 mRNA expression values and full length Alu RNA levels in MAP AD patients (ns=non-significant, with p value 0.05 as the significance threshold). Statistical test as in subfigure 8E.",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "A FACS profiles of DNA content for cells arrested at different points in the cell cycle by Dup/Cdt1 RNAi, cyclin E RNAi, Cdk2 RNAi, Dacapo overexpression (+Dacapo), and 1 mM HU.",
    "ncbi_link": "Cdk2: 42453
cyclin E: 34924
Dacapo: 36001
Cdt1: 47121
Dup: 47121"
  },
  {
    "caption": "Cell cycle analysis by FACS of cells arrested in G1 by Dacapo overexpression followed by release back into the cell cycle for 13 h (top). Western blot analysis of Mcm2‐7 and Orc2 for the nuclear chromatin and cytoplasmic fractions of Mcm2‐7, Orc2, and Dacapo.",
    "ncbi_link": "Dacapo: 36001"
  },
  {
    "caption": "C Western blot analysis for Orc2 and Mcm2‐7 in the nuclear chromatin fraction and Orc2, Mcm2‐7, Dup/Cdt1, and cyclin E in the cytoplasmic fraction for each condition assayed.",
    "ncbi_link": "cyclin E: 34924
Cdt1: 47121
Dup: 47121"
  },
  {
    "caption": "A Genome‐wide analysis of ORC localization by ChIP‐chip. ORC enrichment from asynchronous cells is depicted for a 5‐Mb section of chromosome 2L.B Genome‐wide analysis of Mcm2‐7 localization in early G1 by ChIP‐chip. Mcm2‐7 enrichment from cyclin E RNAi‐depleted cells is depicted for a 5‐Mb section of chromosome 2L.C Venn diagram depicting the overlap between ORC and Mcm2‐7 peaks.",
    "ncbi_link": "cyclin E: 34924"
  },
  {
    "caption": " qRT-PCR analysis of INH1 mRNA levels. Data are mean ± SD from three biological replicates. ",
    "ncbi_link": "INH1: 851347"
  },
  {
    "caption": "Deletion of INH1 benefits the proliferation of ρ0 cells at 37 ℃. Serial dilutions (tenfold dilution) of the indicated strains were analyzed on SCD plates at 30℃ and 37 ℃ for 2 days.",
    "ncbi_link": "INH1: 851347"
  },
  {
    "caption": " Western blot analysis of copper-inducible overexpression of Inh1. A cassette expressing Inh1 under the control of CUP1 promoter was inserted into the HO locus. Inh1 overexpression was induced by 100 μM CuSO4 for 12 hours. ",
    "ncbi_link": "CUP1: 856450
Inh1: 851347"
  },
  {
    "caption": " Overexpression of Inh1 decreases ∆ψm in ρ0 cells. Cells were cultured in SCD or SCD plus 100 μM CuSO4 for 12 hours to mid-log phase. Cells were then stained with 125 nM TMRM for FACS analysis. ",
    "ncbi_link": "Inh1: 851347"
  },
  {
    "caption": " Overexpression of Inh1 represses the proliferation of ρ0 cells. Serial dilutions (tenfold dilution) of the indicated strains were analyzed on SCD or SCD plus 100 μM CuSO4 plates at 30℃ for 2 days. ",
    "ncbi_link": "Inh1: 851347"
  },
  {
    "caption": " Overexpression of Inh1 reduces the protein levels of mitochondrial ISC biosynthesis proteins (Nfs1 and Yah1) and nuclear ISC-containing protein Pol3. Cells were cultured in SCD or SCD plus 100 μM CuSO4 for 12 hours to mid-log phase. Whole cell lysates were extracted and equal amount of proteins was loaded for western blot. Nfs1, Yah1 were endogenously tagged with FLAG, and Pol3 was endogenously tagged with HA. ",
    "ncbi_link": "Inh1: 851347"
  },
  {
    "caption": " The changes of Puf3-associated transcripts encoding mitochondrial proteins in OXPHOS mutants. The RNAseq results in Figure 1C (Dataset EV1) are re-analyzed. Transcripts encoding high fidelity mitochondrial proteins (gene list in Table EV1A) and the Puf3-associated transcripts encoding mitochondrial proteins (gene list in Table EV1D) are shown. The significantly changed transcripts (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed transcripts are indicated. ",
    "ncbi_link": "Puf3: 850647"
  },
  {
    "caption": " B and C, Deletion of PUF3 upregulates mitochondrial transcripts in WT cells (B), whereas downregulates mitochondrial transcripts in ρ0 cells (C). WT and mutant yeast cells were cultured to log phase. RNAseq was performed with three biological replicates per genotype (Dataset EV4). All the transcripts and the Puf3-associated transcripts encoding mitochondrial proteins are shown. The significantly changed transcripts (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed transcripts are indicated. ",
    "ncbi_link": "Puf3: 850647
PUF3: 850647"
  },
  {
    "caption": " D. Deletion of PUF3 in ρ0 cells downregulates mitochondrial proteins. SILAC analysis of mitochondrial fractions from ρ0 and ρ0 puf3∆ cells are shown. Equal amount of ρ0 cells labeled with heavy amino acids and unlabeled ρ0 puf3∆ cells were mixed to extract mitochondrial fraction for mass-spectrometry analysis. Three biological replicates were prepared for each pair of strains (Dataset EV5). Mitochondrial proteins encoded by Puf3-associated mRNAs are highlighted in red. Mia40 substrates are highlighted in green (gene list in Table EV1E). Mia40 substrates encoded by Puf3 associated transcripts are highlighted in green with red circle. The significantly changed proteins (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed proteins are indicated. ",
    "ncbi_link": "Puf3: 850647
puf3: 850647
PUF3: 850647"
  },
  {
    "caption": " E. Correlation plots of fold changes (ρ0 puf3∆ versus ρ0) between mitochondrial proteins and their transcripts. Puf3-associated transcripts encoding mitochondrial proteins are highlighted in red. Mia40 substrates are highlighted in green. Mia40 substrates encoded by Puf3 associated transcripts are highlighted in green with red circle. ",
    "ncbi_link": "Mia40: 853639
Puf3: 850647
puf3: 850647"
  },
  {
    "caption": " F. Deletion of PUF3 decreases ∆ψm in ρ0 cells. Cells were cultured to mid-log phase, and stained with 125 nM TMRM for FACS analysis ",
    "ncbi_link": "PUF3: 850647"
  },
  {
    "caption": " G. Deletion of PUF3 decreases the proliferation of ρ0 cells. Serial dilutions (tenfold dilution) of the indicated strains were analyzed on SCD plates at 30℃ for 2 days. ",
    "ncbi_link": "PUF3: 850647"
  },
  {
    "caption": " H. Schematic illustration of the consensus Puf3-binding motif Lapointe et al., 2015() and the motif at Mia40 3'-UTR. Mutating the Puf3-binding motif of MIA40 mRNA abolishes Mia40 upregulation in ρ0 cells. Mia40 was endogenously tagged with FLAG and its 3'-UTR was edited as indicated. The selection markers were removed by the Cre-loxP system. Whole cell lysates were extracted and equal amount of proteins was loaded for western blot. RC: reverse complement. DE: deletion. ",
    "ncbi_link": "Mia40: 853639
MIA40: 853639"
  },
  {
    "caption": " I. Mutating the Puf3-binding motif of MIA40 mRNA decreases ∆ψm of ρ0 cells. J. Mutating the Puf3-binding motif of MIA40 mRNA impairs the proliferation of ρ0 cells. Cells were cultured from 0.05 OD in SCD, and OD600 was measured every 2 hours. Cells were cultured to mid-log phase, and stained with 125 nM TMRM for FACS analysis",
    "ncbi_link": "MIA40: 853639"
  },
  {
    "caption": " K. Overexpression of MIA40 rescues ∆ψm of ρ0 puf3∆ cells. Single copy plasmid expressing Mia40 driven by the MIA40 promoter was transformed into the indicated strains. L. Overexpression of MIA40 rescues the proliferation of ρ0 puf3∆ cells. Strains were prepared as in (K). Cells were cultured from 0.05 OD in SCD, and OD600 was measured every 2 hours. Cells were cultured to mid-log phase, and stained with 125 nM TMRM for FACS analysis",
    "ncbi_link": "Mia40: 853639
MIA40: 853639
puf3: 850647"
  },
  {
    "caption": " Puf3-15A mutation inhibits Puf3 hyper-phosphorylation in ρ0 cells. A cassette expressing WT or mutant Puf3-FLAG (11A or 15A) under the control of PUF3 promoter was inserted into the HO site in puf3∆ cells. The 15A mutant that blocks Puf3 hyper-phosphorylation is highlighted in red. Puf3-FLAG was immunoprecipitated from the indicated strains and analyzed by regular and Phos-tag SDS-PAGE. ",
    "ncbi_link": "FLAG: 
Puf3: 850647
PUF3: 850647
puf3: 850647"
  },
  {
    "caption": " Puf3-15A mutation inhibits Puf3 hyper-phosphorylation upon oligomycin treatment and in ∆V and ρ0 cells. WT cells were treated with antimycin (10 μM), KCN (10 μM) or oligomycin (10 μM) for 3 hours, or shifted from SCD to SCEG medium for 3 hours. Whole cell lysates were extracted and equal amount of proteins was loaded for western blot. Asterisk indicates a non-specific band. ",
    "ncbi_link": "Puf3: 850647"
  },
  {
    "caption": " Puf3-15A mutation downregulates Puf3-associated mitochondrial transcripts in ρ0 cells. ρ0 and ρ0 puf3-15A cells were cultured to log phase. RNAseq was performed with three biological replicates per genotype (Dataset EV7). All the transcripts and the Puf3-associated transcripts encoding mitochondrial proteins (gene lists in Table EV1D) are shown. The significantly changed transcripts (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed transcripts are indicated. ",
    "ncbi_link": "puf3: 850647
Puf3: 850647"
  },
  {
    "caption": "Puf3-15A mutation inhibits the upregulation of Mia40 in ∆V and ρ0 cells. Mia40 was endogenously tagged with FLAG. The selection markers were removed by the Cre-loxP system. Whole cell lysates were extracted and equal amount of proteins was loaded for western blot.",
    "ncbi_link": "Mia40: 853639
Puf3: 850647"
  },
  {
    "caption": " Puf3-15A mutation decreases ∆ψm in ρ0 cells. Cells were cultured to mid-log phase and stained with 125 nM TMRM for FACS analysis. The red ] highlight two cell lines for comparison. ",
    "ncbi_link": "Puf3: 850647"
  },
  {
    "caption": " Puf3-15A mutation has no effect on the proliferation of WT cells.   Puf3-15A mutation inhibits the proliferation of ρ0 cells.   Mia40 overexpression rescues the proliferation defect of ρ0 puf3-15A cells. Single copy plasmid expressing Mia40 driven by MIA40 promoter was transformed into the indicated strains.   ",
    "ncbi_link": "Mia40: 853639
MIA40: 853639
Puf3: 850647
puf3: 850647"
  },
  {
    "caption": " Snf1 maintains glycolysis and glucose transporter gene expression in both WT and ρ0 cells, and represses ribosome and Ribi gene expression in ρ0 cells. ρ0 snf1∆ cells were prepared by acute EtBr (25 µg/ml) treatment of snf1∆ cells in SCD for 2 days. RNAseq was performed with three biological replicates per genotype (Dataset EV8). All the transcripts and two categories of transcripts (gene lists in Table EV1B) are shown. Significantly changed genes (P value < 0.05; fold change > 1.5 or < 0.67) are highlighted with dashed lines; numbers of significantly changed genes are indicated. ",
    "ncbi_link": "Snf1: 852088
snf1: 852088"
  },
  {
    "caption": " Snf1 represses ribosome biogenesis in WT and ρ0 cells. Polysomes of the indicated strains were fractionated by sucrose gradients (10%-50%), and the gradients were separated and measured at A254. ",
    "ncbi_link": "Snf1: 852088"
  },
  {
    "caption": " Deletion of SNF1 decreases ∆ψm in both ∆V and ρ0 cells. Cells were cultured to mid-log phase and stained with 125 nM TMRM for FACS analysis ",
    "ncbi_link": "SNF1: 852088"
  },
  {
    "caption": " Deletion of SNF1 decreases the proliferation of both ∆V and ρ0 cells. Serial dilutions of the indicated strains were analyzed on SCD plates at 30℃ for 2 days. ",
    "ncbi_link": "SNF1: 852088"
  },
  {
    "caption": " Deletion of MIG1 in ρ0 snf1∆ cells rescues ∆ψm. Cells were cultured to mid-log phase and stained with 125 nM TMRM for FACS analysis ",
    "ncbi_link": "MIG1: 852848
snf1: 852088"
  },
  {
    "caption": " Deletion of MIG1 in ρ0 snf1∆ cells partially rescues cell proliferation. A plasmid overexpressing MIG1 under the control of MIG1 promoter was transformed into the indicated strains. Serial dilutions (tenfold dilution) were analyzed on SCD plates at 30℃ for 2 days. V: empty vector. ",
    "ncbi_link": "MIG1: 852848
snf1: 852088"
  },
  {
    "caption": " Combining MIG1 deletion and NOG2 overexpression in ρ0 snf1∆ cells fully rescues cell proliferation. A plasmid overexpressing NOG2 under the control of TEF1 promoter was transformed into the indicated strains. Serial dilutions (tenfold dilution) were analyzed on SCD plates at 30℃ for 2 days. V: empty vector. ",
    "ncbi_link": "MIG1: 852848
NOG2: 855789
snf1: 852088
TEF1: 856195"
  },
  {
    "caption": " Deletion of HSC82 selectively impairs the proliferation of ρ0 puf3∆ cells. Cells were cultured from 0.05 OD in SCD, and OD600 was measured every 2 hours. Data are mean ± SD from three biological replicates. ",
    "ncbi_link": "HSC82: 855224
puf3: 850647"
  },
  {
    "caption": " Deletion of HSC82 selectively decreases ∆ψm in ρ0 puf3∆ cells. Cells were cultured to mid-log phase and stained with 125 nM TMRM for FACS analysis. The red ] highlight two cell lines for comparison. ",
    "ncbi_link": "HSC82: 855224
puf3: 850647"
  },
  {
    "caption": "(A) incorporation of 14C-labeled  glycerol 3-phosphate  (G3P) into various lipids in the presence of  palmitoyl-CoA  (10 µM) in microsomal membranes   prepared from HEK293-AT1  cells. After incubations at room temperature for 30 min, lipids were extracted and separated by TLC  before quantification using autoradiography and phosphorimaging. Lipid species corresponding to the major spots visualized are indicated. Note the appearance of phosphatidylcholine (PC) and cytidine diphosphate-diacylglycerol  (CDP-DAG) in the presence of  cytidine trisphosphate (CTP), as well as the production of phosphatidylinositol  (PI) only when both CTP  and myo-inositol  are present. Also, there is a relatively small effect of the DAG kinase inhibitor (DGKi) on CDP-DAG and PI  formation in spite of the fact that plenty of phosphatidic acid (PA) is available from de novo synthesis (although it should be noted that no ATP  was added during these reactions). A representative experiment is shown, but these results have been reproduced in other replicates using different treatment combinations. The insert shows the effect of the DGK  inhibitor on PI  labeling.",
    "ncbi_link": "AT1: 24180"
  },
  {
    "caption": "(B) Effect of lipin-1γ overexpression on the metabolic fate  of de novo synthesized PA. Experiments were performed as in panel A, except that the membranes were also prepared from cells expressing a GFP-tagged lipin 1γ, as indicated. Note the large amount of TG  and increased production of PC  under these conditions. Results of a representative experiment are shown, and these experiments were repeated with identical results.",
    "ncbi_link": "GFP: 
lipin 1γ: 23175
lipin-1γ: 23175"
  },
  {
    "caption": "Lgr5fl/fl/Axin2CreErt2 (Lgr5-/-) and control mice  were infected for 2 months with H. pylori. A Representative H&E staining  from antral  glands  (upper row). The dotted line marks the gland base cell   area, which expands upon infection in  Lgr5-/- and control mice. Immunofluorescence  labeling for GSII  and Ki67  (middle row) and GIF  and Muc5ac  (lower row) of antral epithelium   from  Lgr5-/- and control mice  uninfected and after 2 months of infection. Scale bars: 50 µm.",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Lgr5fl/fl/Axin2CreErt2 (Lgr5-/-) and control mice were infected for 2 months with H. pylori. B Quantification of antral gland  height in  Lgr5-/- compared to control mice. Uninfected control (n = 5) versus uninfected Lgr5-/- (n = 4) versus infected control (n = 4) versus infected Lgr5-/- (n = 4). Data information: B, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; ns = not significant (one-way ANOVA + Tukey´s multiple comparison test for B,",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Lgr5fl/fl/Axin2CreErt2 (Lgr5-/-) and control mice  were infected for 2 months with H. pylori. C Quantifications of GSII+ area (n = 4-5 biological replicates per group, n = 10 glands per mouse), Ki67  as percentage of total DAPI-stained  cells (n = 3-4 biological replicates per group, n = 20 glands  per mouse), GIF+ area (n = 4-5 biological replicates per group, n = 10 glands  per mouse), Muc5ac+ area (n = 4-5 biological replicates per group, n = 10 glands  per mouse). Data information: For (one-way ANOVA + Tukey´s multiple comparison test for C,",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Lgr5fl/fl/Axin2CreErt2 (Lgr5-/-) and control mice  were infected for 2 months with H. pylori. D H. pylori CFUs in Lgr5-/- (n = 5) and control mice  (n = 5). Data information: For D, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; ns = not significant t-test for D",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Lgr5fl/fl/Axin2CreErt2 (Lgr5-/-) and control mice  were infected for 2 months with H. pylori. E qPCR  expression levels of Lgr4, Lgr5, Axin2, gland base cell  markers (Gif, Pgc, Tff2, Muc6), pit cell  marker Muc5ac, and Itln1  in uninfected  Lgr5-/- (n = 6-10) and control mice  (n = 4-10). F qPCR  expression levels of Lgr4, Lgr5, gland base cell   markers (Gif, Pgc, Muc6), and Itln1  in Lgr5-/- (n = 5) and control mice  (n = 5) after 2 months of infection. Data information: For E and F, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; ns = not significant t-test for E and F).",
    "ncbi_link": "Axin2: 12006
Gif: 14603
Cre: 2777477
Ert2: 2099
Itln1: 16429
Lgr4: 107515
Lgr5: 14160
Muc5ac: 17833
Muc6: 353328
Pgc: 109820
Tff2: 21785"
  },
  {
    "caption": "Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) and control mice  were infected for 2 months with H. pylori. A Representative H&E staining  from antral glands (upper row). The dotted line marks the gland base cell area, which does not expand in infected Lgr4-/- but does expand in the corresponding control mice. Immunofluorescence labeling for GSII  and Ki67  (middle row) and GIF  and Muc5ac  (bottom row) of  antral epithelium  from Lgr4-/- and control mice  uninfected and after 2 months of infection. Scale bars: 50 µm.",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr4: 107515"
  },
  {
    "caption": "Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) and control mice  were infected for 2 months with H. pylori. B Quantification of antral gland height in Lgr4-/- compared to control mice. Uninfected control (n = 2) versus uninfected Lgr4-/- (n = 4) versus infected control (n = 4) versus infected Lgr4-/- (n = 4). Data information: For B, , data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001; ns = not significant (one-way ANOVA + Tukey´s multiple comparison test for B",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr4: 107515"
  },
  {
    "caption": "Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) and control mice  were infected for 2 months with H. pylori. C Quantifications of GSII+ area (n = 2-4 biological replicates per group, n = 10 glands  per mouse), Ki67  as percentage of total DAPI-stained  cells (n = 2-4 biological replicates per group, n = 20 glands  per mouse), GIF+ area (n = 2-4 biological replicates per group, n = 10 glands  per mouse), Muc5ac+ area (n = 4-5 biological replicates per group, n = 10 glands  per mouse). Data information: For C, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001; ns = not significant (one-way ANOVA + Tukey´s multiple comparison test for C,",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr4: 107515"
  },
  {
    "caption": "Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) and control mice  were infected for 2 months with H. pylori. D H. pylori CFUs show higher colonization  in Lgr4-/- (n = 5) compared to control mice  (n = 4). Data information: For D, , data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001; ns = not significant t-test for D",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr4: 107515"
  },
  {
    "caption": "Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) and control mice  were infected for 2 months with  H. pylori. E qPCR  expression levels of Lgr4, Lgr5, Axin2, gland base cell  markers (Gif, Pgc, Tff2, Muc6), pit cell  marker Muc5ac, and Itln1  in uninfected Lgr4-/- (n = 4-10) and control mice  (n = 4-6). F qPCR  expression levels of Lgr4, Lgr5, gland base cell markers (Gif, Pgc, Muc6), and Itln1 in Lgr4-/- (n = 5) and control mice  (n = 5) after 2 months of infection. Data information: For E and F, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001; ns = not significant t-test for E and F).",
    "ncbi_link": "Axin2: 12006
Gif: 14603
Cre: 2777477
Ert2: 2099
Itln1: 16429
Lgr4: 107515
Lgr5: 14160
Muc5ac: 17833
Muc6: 353328
Pgc: 109820
Tff2: 21785"
  },
  {
    "caption": "A, B GSEA  comparing microarray   data from 2-month infected Lgr4fl/fl/Axin2CreErt2 (Lgr4-/-) mice  with publicly available data demonstrating downregulation of antral stem cell  signature (A) and beta-catenin targets (B).",
    "ncbi_link": "Axin2: 12006
Cre: 2777477
Ert2: 2099
Lgr4: 107515"
  },
  {
    "caption": "C qPCR  expression levels for beta catenin targets Axin2  and Sox9  in uninfected and infected  Lgr4-/- and control mice  (n = 2-9). Data information: For C, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (one-way ANOVA + Tukey´s multiple comparison test).",
    "ncbi_link": "Axin2: 12006
Lgr4: 107515
Sox9: 20682"
  },
  {
    "caption": "D GSEA  comparing microarray  data from 2-month infected Lgr4-/- mice  with publicly available data demonstrating downregulation of the TNF-α signaling via NF-κB.",
    "ncbi_link": "Lgr4: 107515"
  },
  {
    "caption": "E Immunofluorescence  labeling for p65, Ki67  and GSII  in the mouse antrum  tissue from uninfected and infected Lgr4-/- and control mice. Insets show magnified images. Scale bars: 50 µm.",
    "ncbi_link": "Lgr4: 107515"
  },
  {
    "caption": "F Quantification of p65+ area as percentage of total DAPI-stained  cells of uninfected and infected Lgr4-/- and control mice  (n = 4 biological replicates per group, n = 20 glands  per mouse). Data information: For data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (one-way ANOVA + Tukey´s multiple comparison test).",
    "ncbi_link": "Lgr4: 107515"
  },
  {
    "caption": "G Immunofluorescence co-localization of p65 acetyl  K310 (activated form of NF-κB) in the mouse antrum  tissue of infected Lgr4-/- and in control mice. Insets show magnified images. Scale bars: 50µm. Data information: For G images represent findings that were reproduced at least twice in the laboratory in independent biological replicates.",
    "ncbi_link": "Lgr4: 107515"
  },
  {
    "caption": "H qPCR  expression levels of Cxcl1, Cxcl2, Cxcl10, Ccl2  in uninfected and infected Lgr4-/- mice  (n = 4-5) and control mice  (n = 2-5). Data information: For H, data are mean + SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (one-way ANOVA + Tukey´s multiple comparison test).",
    "ncbi_link": "Ccl2: 20296
Cxcl1: 14825
Cxcl10: 15945
Cxcl2: 20310
Lgr4: 107515"
  },
  {
    "caption": "I Immunofluorescence labeling for Cxcl1  in the mouse antrum  tissue in infected Lgr4-/- and in control mice. Scale bars: 50 µm. Data information: For I images represent findings that were reproduced at least twice in the laboratory in independent biological replicates.",
    "ncbi_link": "Lgr4: 107515"
  },
  {
    "caption": "A Immunofluorescence  labeling for p65  and E-cadherin in the mouse antrum  tissue of 2 weeks infected B6-Myh11CreErt2/Rspondin3fl/fl (Rspo3-/-) and control mice. Arrows in infected control mice  indicate nuclear p65  that is not observed in Rspo3-/- mice. Scale bars: 50 µm.",
    "ncbi_link": "Cre: 2777477
Ert2: 2099
Myh11: 17880
Rspo3: 72780
Rspondin3: 72780"
  },
  {
    "caption": "B Quantification of p65+ area as percentage of total DAPI-stained  cells of infected Rspo3-/- and control mice  (n = 3 biological replicates per group, n = 20 glands  per mouse). Data information: For B, data are mean + SD. * = p < 0.05; ** = p < 0.01; ns = not significant (t-test for B",
    "ncbi_link": "Rspo3: 72780"
  },
  {
    "caption": "C qPCR  expression level of Cxcl1  and Cxcl2  in 2-week infected Rspo3-/- mice  (n = 3) versus infected control mice  (n = 4). D qPCR  expression level of Cxcl1  and Cxcl2  in 2-month infected Rspo3-/- mice  (n = 5) versus infected control mice  (n = 6). Data information: For C, D, data are mean + SD. * = p < 0.05; ** = p < 0.01; ns = not significant (t-test for C and D",
    "ncbi_link": "Cxcl1: 14825
Cxcl2: 20310
Rspo3: 72780"
  },
  {
    "caption": "E Myh11CreERT2/Rosa26Sor6(CAG-Rspo3) (Rspo3 KI) mice  were infected for 6 weeks with H. pylori. Immunofluorescence  labeling for p65, GSII  and KI67  in uninfected and infected Rspo3 KI and control mice. Scale bars: 50 µm. F Quantification of p65+ area as percentage of total DAPI-stained  cells of uninfected and infected Rspo3 KI and control mice  (n = 2-3 biological replicates per group, n = 20 glands  per mouse). G Quantification of GSII+ area of uninfected and infected Rspo3 KI and control mice  (n = 2-3 biological replicates per group, n = 20 glands  per mouse). H Quantification of Ki67  as percentage of total DAPI-stained  cells of uninfected and infected Rspo3  KI and control mice  (n = 2-3 biological replicates per group, n = 20 glands  per mouse). Data information: For , F, G and H data are mean + SD. * = p < 0.05; ** = p < 0.01; ns = not significant one-way ANOVA + Tukey´s multiple comparison test for F, G and H).",
    "ncbi_link": "Cre: 2777477
ERT2: 2099
Rosa26Sor: 14910
Myh11: 17880
Rspo3: 72780"
  },
  {
    "caption": "I Immunofluorescence  labeling for p65 acetyl  K310 in infected Rspo3 KI and control mice. Insets show magnified images. Scale bars: 50 µm.",
    "ncbi_link": "Rspo3: 72780"
  },
  {
    "caption": "A Immunofluorescence  labelling for MPO  in uninfected and 2-month infected  Lgr4-/- and control mice  (top panel) and 2-month infected Lgr5-/- and control mice  (bottom panel). Asterisks indicate nonspecific staining. Scale bars: 50 µm. B Quantification of MPO+ cells in uninfected and 2-month infected Lgr4-/- and control mice  (n = 2 biological replicates per group, n = 5-10 FOVs per mouse) (left panel) and 2-month infected Lgr5-/- and control mice  (n = 2 biological replicates per group, n = 6-8 FOVs per mouse) (right panel). Data information: For B data are mean + SD. ** = p < 0.01; *** = p < 0.001; ns = not significant (one-way ANOVA + Tukey´s multiple comparison test).",
    "ncbi_link": "Lgr4: 107515
Lgr5: 14160"
  },
  {
    "caption": "Antrum organoids  from wildtype mice were grown in full medium (FM) for 2-3 days, followed by respective medium conditions for 3-5 days (FM, -Rspo, -Rspo/-Wnt, +BMP2). C qPCR  expression level of Lgr5  in untreated organoids  in respective medium conditions (n = 4-5 biological replicates). D qPCR  expression level of Gif  in untreated organoids  in respective medium conditions (n = 4-5 biological replicates). Data information: For C, D, data are mean + SD. * = p < 0.05; ** = p < 0.01; **** = p < 0.0001 (one-way ANOVA + Tukey´s multiple comparison test for C and Genes without asterisks are not significantly altered.",
    "ncbi_link": "Gif: 14603
Lgr5: 14160"
  },
  {
    "caption": "Antrum organoids  from wildtype mice  were grown in full medium (FM) for 2-3 days, followed by respective medium conditions for 3-5 days (FM, -Rspo, -Rspo/-Wnt, +BMP2). 0.5 µM ADP heptose or 10 ng/ml TNF-α  was added for 2 h to all organoid  conditions prior to analysis. E qPCR  expression level of Cxcl1, Cxcl2, Cxcl10, Ccl2  in organoids  after treatment with ADP heptose compared to untreated controls within the respective medium conditions (n = 6 biological replicates per condition). F qPCR  expression level of Cxcl1, Cxcl2, Cxcl10, Ccl2 in organoids  after treatment with TNF-α compared to untreated controls within the respective medium conditions (n = 2-3 biological replicates per condition). Data information: For E and F data are mean + SD. * = p < 0.05; ** = p < 0.01; **** = p < 0.0001 ; t-test for E and F). Genes without asterisks are not significantly altered.",
    "ncbi_link": "Ccl2: 20296
Cxcl1: 14825
Cxcl10: 15945
Cxcl2: 20310"
  },
  {
    "caption": "A  Bright-field images of antrum organoids  from 129;129P2-ctnnb1tm(NFKBIAΔN)1Rsu (ΔN) mice  and control mice, passage 0, day 6. Scale bars: 500 µm.",
    "ncbi_link": "ctnnb1: 12387
NFKBIA: 18035"
  },
  {
    "caption": "B, C qPCR  expression levels of Lgr4, Lgr5, Gif, Pgc, Muc6  (B) and Cxcl1, Cxcl2  (C) of organoids  (n = 3 biological replicates). Data information: For B, C, data are mean + SD. * = p < 0.05; ** = p < 0.01; ns = not significant (t-test).",
    "ncbi_link": "Gif: 14603
Cxcl1: 14825
Cxcl2: 20310
Lgr4: 107515
Lgr5: 14160
Muc6: 353328
Pgc: 109820"
  },
  {
    "caption": "A) Macrophages were transduced with non-specific scrambled shRNA (shNS), or TLR8 shRNA (shTLR8) and analyzed for TLR8 expression. Bottom, a representative blot is shown. Top, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "(B) Macrophages transduced with shNS or shTLR8 from (A) were exposed to infectious HIV (+), AT-2-inactivated HIV (AT), or RNase/DNase I treated AT-2-inactivated HIV (R) or mock infected (-) for 24 h, harvested, lysed and analyzed for endogenous LC3B and SQSTM1 by Western blotting. Left, a representative blot is shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "(D) Macrophages were transduced with shNS or ATG13 shRNA (shATG13) and analyzed for ATG13 expression. Bottom, a representative blot is shown. Top, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "(E) Macrophages transduced with shNS or shATG13 from (D) were exposed to infectious HIV, 5 μg/mL ssRNA40, 5 μg/mL ssRNA41, or 100 nmol/L sirolimus for 24 h, harvested, lysed and analyzed for endogenous LC3B and SQSTM1 by Western blotting. Left, a representative blot is shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "(E) Macrophages were transduced with non-specific scrambled shRNA (shNS), or TLR8 shRNA (shTLR8) and analyzed for TLR8 expression. Bottom, a representative blot is shown. Top, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "(F) Macrophages transduced with shNS or shTLR8 from (E) were exposed to mock, infectious, AT-2-inactivated, or RNase/DNase I treated AT-2-inactivated purified HIV for 24 h. Cells were then harvested, lysed, fractionated for cytoplasmic and nuclear content, and analyzed for TFEB, ACTB and H3 histone by Western blotting. Top, a representative blot is shown. Bottom, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "(A) Macrophages transduced with non-specific scrambled shRNA (shNS), or TFEB shRNA (shTFEB) were infected with HIV for 10 days. Cells were lysed and analyzed for TFEB and ACTB content by Western blotting. Left, a representative blot is shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(C) Macrophages transduced with non-specific cDNA (Control), or TFEB cDNA (TFEB) then exposed to HIV. Cells were lysed and analyzed for TFEB and ACTB content by Western blotting. Bottom, a representative blot is shown. Top, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A) qRT-PCR analysis of mRNA expression of autophagy (UVRAG and ATG9B) and lysosomal (MCOLN1) genes 24 h post-exposure to mock, infectious, or RNase/DNase I treated AT-2-inactivated purified HIV. Data are reported as mean ± s.e.m., n = 4.",
    "ncbi_link": "ATG9B: 285973
MCOLN1: 57192
UVRAG: 7405"
  },
  {
    "caption": "(B) Macrophages were transduced with non-specific scrambled shRNA (shNS), or TLR8 shRNA (shTLR8) and analyzed for TLR8 expression. Bottom, a representative blot is shown. Top, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "TLR8: 51311"
  },
  {
    "caption": "(C) Macrophages from (B) were exposed to mock, infectious, or RNase/DNase I treated AT-2-inactivated purified HIV for 24 h. Cells were harvested and qRT-PCR for UVRAG, ATG9B, MCOLN1 was performed. Data were normalized to the shNS mock infected control for each gene. Bar charts are reported as mean ± s.e.m., n = 4.",
    "ncbi_link": "ATG9B: 285973
MCOLN1: 57192
UVRAG: 7405"
  },
  {
    "caption": "(A) Macrophages transduced with non-specific scrambled shRNA (shNS), or BECN1 shRNA (shBECN1) were infected with HIV for 10 days. Cells were lysed and analyzed for BECN1 and ACTB content by Western blotting. Left, a representative blot is shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "BECN1: 8678"
  },
  {
    "caption": "(A) Macrophages were infected with HIVNL(AD8) or HIVNL(AD8)ΔNef. At 1, 3, 5, 7, and 10 days post-infection cells were harvested, lysed and analyzed for endogenous LC3B, SQSTM1, and ACTB by Western blotting. Left, representative blots are shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "Nef: 156110"
  },
  {
    "caption": "(B) Macrophages were infected with HIVNL(AD8) or HIVNL(AD8)ΔNef. At 1, 3, 5, 7, and 10 days post-infection cells were harvested, lysed, fractionated for cytoplasmic and nuclear content, and analyzed for TFEB, ACTB and H3 histone by Western blotting. Left, representative blots are shown. Right, densitometric analysis of immunoblots from independent donors presented as means ± s.e.m., n = 4.",
    "ncbi_link": "Nef: 156110"
  },
  {
    "caption": "WB in Tg-APP total brain lysates on 4-12% NuPAGE SDS gel (Invitrogen) show total Abl (top blot) T412 Abl (2nd blot), soluble parkin level (3rd blot), and LC3 (4th blot) relative to MAP-2 (N = 9).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Quantitative ELISA showing soluble (STEN extract) and insoluble (4 M urea extract) mouseparkin in Tg-APP (N = 9). Parkin−/−brains were used as a specificity control.",
    "ncbi_link": "APP: 351
Parkin: 50873"
  },
  {
    "caption": "In situ proximity ligation assay (PLA) shows endogenous parkin-Beclin-1 complexes in (G) WT C57BL/6mice (N = 5) and (H) parkin−/− as control.PLA in Tg-APPmice IP injected once daily for 3 weeks with (I) DMSO (J) 5 mg/kg Bosutinib and (K) 10 mg/kg Nilotinib (N = 5).",
    "ncbi_link": "APP: 351
parkin: 50873"
  },
  {
    "caption": "Graph represents human Aβ1-42ELISA in rat B35 neuroblastoma cells transfected with human cDNA Aβ1-42 (or LacZ) or Beclin-1 shRNA for 24 hr, and then treated with 1 μM Bosutinib for an additional 24 hr (N = 12). *Significantly different to control or as indicated, Mean ± SEM, ANOVA with NeumannKeuls multiple comparison.",
    "ncbi_link": "Aβ: 351
Beclin-1: 8678"
  },
  {
    "caption": "Staining of 20 μm brain sections shows plaque formation with 6E10 antibody and DAB in the brain in different (A,B) Tg-APP + DMSO and (C) thioflavin-S staining in Tg-APP treated with DMSO (N = 7). (D,E) Tg-APP treated with 5 mg/kg Bosutinib for 3-weeks and (F) thioflavin-s staining.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Staining of 20 μm thick brain sections shows (G) parkin, (H) Aβ1-42 and (I) merged figure in cortex of Tg-APPmice after 3 weeks of DMSO treatment, and (J) parkin, (K) Aβ1-42 and (L) merged figure in cortex of Tg-APPmice after 3 weeks of 5 mg/kg Bosutinib treatment. (M) Parkin, (N) Aβ1-42 and (O) merged figure in hippocampus of Tg-APPmice after 3 weeks of DMSO treatment, and (P) parkin, (Q) Aβ1-42 and (R) merged figure in cortex of Tg-APPmice after 3 weeks of Bosutinib treatment (N = 7).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(S) Graphs represent quantification of amyloidplaques in Tg-APP with and without Bosutinib.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "WB in Tg-APP total brain lysates on 4-12% NuPAGE SDS gel (Invitrogen) showing (T) levels of BACE1 (1st blot), ADAM-10 (2nd blot) and presinilin-1 (3rd blot) relative to actin",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "WB in Tg-APP total brain lysates on 4-12% NuPAGE SDS gel (Invitrogen) showing (U) total APP (top blot), CTFs (2nd blot) and phospho-tyrosine (3rd blot) relative to actin (N = 9).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Graphs represent ELISA of human Aβ1-42 in (A) brain levels and (B) bloodAβ1-42 levels in 8-month old Tg-APPmice injected I.P. every other day for 6 weeks with Bosutinib or Nilotinib (N = 10).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "ELISA of human soluble and insoluble brain (C) Aβ1-42 and (D) Aβ1-40 levels in 8-month old Tg-APPmice injected IP daily for 3 weeks with 5 mg/kg Bosutinib (N = 9).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "ELISA of (E) mouse p-Tau levels in 8-month old Tg-APP mice injected IP daily for 3 weeks with 5 mg/kg Bosutinib (N = 9).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "WB in Tg-APP total brain lysates on 4-12% NuPAGE SDS gel (Invitrogen) show total Tau (1st blot), serine 396 p-Tau (2nd blot), threonine 231 (AT180, 3rd blot) and serine 199 p-Tau (AT8, 4th blot) relative to actin (N = 7).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "WB on 4-12% NuPAGE SDS gel of total brain lysates in 1 year old wild type and parkin−/−mice treated with 5 mg/kg Bosutinib for 3 weeks on 4-12% NuPAGE SDS gel (Invitrogen) showing parkin (1st blot)total Abl (2nd blot), T412 Abl (3rd blot), Beclin-1 (4th blot) and LC3 (5th blot) relative to actin (N = 7).",
    "ncbi_link": "parkin: 50873"
  },
  {
    "caption": "Staining of 20μm brain sections shows plaque formation with 6E10 antibody and DAB 6 weeks post-injection with (G) lentiviralAβ1-42 + 3 weeks DMSO treatment and (H) IP injection with 5 mg/kg Bosutinib 3 weeks post-lentiviral expression (3 weeks treatment) clears plaques in WT mice (N = 7).(I) Lentiviral Aβ1-42 + DMSO and (J) IP injection with 5 mg/kg Bosutinib 3 weeks post-lentiviral expression (3 weeks treatment) in parkin−/−mice (N = 7).",
    "ncbi_link": "parkin: 50873"
  },
  {
    "caption": "Graphs represent ELISA (N = 5) in autophagic vacuoles (AVs) in the brain of 4 and 8 months old Tg-APPmice treated with 10 mg/kg Nilotinib or 5 mg/kg Bosutinib (N = 5) for 3 weeks showing (A)humanAβ1-42 (Insert is WB analysis of AVs showing LC3-B in AV10 and AV20 (1st blot) and LAMP2a in Lys (2nd blot) fraction) and (B)Aβ1-40,(C) p-Tau and (D) parkin.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "ELISA in autophagic vacuoles of 1 year old WT and parkin−/−mice (N = 5) injected with lentiviralAβ1-42 for 3 weeks and treated with 10 mg/kg Nilotinib and 5 mg/kg Bosutinib for 3 additional weeks showing (E) humanAβ1-42 and (F) p-Tau levels.",
    "ncbi_link": "parkin: 50873"
  },
  {
    "caption": "(A) Represents results of Morris water maze test in lentiviralAβ1-42-injected ± Bosutinib WT (N = 12) and parkin−/− (N = 10) mice, and (B) heat maps for each group.Graphs represent total number of entry into platform area and distance travelled.",
    "ncbi_link": "Aβ: 351
parkin: 50873"
  },
  {
    "caption": "Represents results of Morris water maze test in Tg-APP ± Bosutinib (N = 12) mice.Graphs represent total number of entry into platform area and distance travelled.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(B-C) Representative confocal images and their quantification of   Gb3  accumulation within the  lysosome, detected by fluorescent-conjugated Shiga toxin, from WT, CLN3-KO and CLN7-KO ARPE-19 cells treated with  PDMP or silenced for Gb3 synthase (siGb3S) (*** vs WT, °°° vs DMSO). Data are presented as mean ± SD, °°°/***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "Gb3 synthase: 53947
Gb3S: 53947
CLN3: 1201
CLN7: 256471"
  },
  {
    "caption": "(A-B) Representative confocal images of Gb3   accumulation, revealed by STX staining, in  brain sections from CLN7Δex2 mice at 3 and 7.5 months of age compared with CLN7 WT mice. Scale bars: 80 µm.",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "(E)  Lipidomic analysis of neurons isolated from CLN7 WT and  CLN7Δex2 mouse forebrain. Data are presented as mean ± SD, **: P ≤ 0.001, ***: P ≤ 0.0001, as determined by ANOVA (n= 3 biological replicas)",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "(A) Representative  confocal images and quantification of SCMAS staining within the lysosome of ARPE-19  WT and  CLN3 KO upon depletion of Gb3S  (siGb3S), LacCer (siLCS), and  GM3s (siGM3S). (*** vs WT, °°° vs CLN3 KO siSCR). Data are presented as mean ± SD, °°°/***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "Gb3S: 53947
LacCer: 9331///9334
LCS: 9331///9334
CLN3: 1201
GM3s: 8869
GM3S: 8869"
  },
  {
    "caption": "(D) Representative  confocal images and quantification of  STX staining within the  lysosome of ARPE-19 WT and  CLN7  KO in DMSO or treated 48h with Tamoxifen. (*** vs WT, °°° vs CLN3  KO  DMSO). Data are presented as mean ± SD, °°°/***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "CLN3: 1201
CLN7: 256471"
  },
  {
    "caption": "(E) Representative confocal images and quantification of  STX staining within the  lysosome  of NPCs WT and derived from CLN7Pa474 patient IPSCs in  DMSO or treated with  Tamoxifen for 48h. (*** vs WT, °°° vs CLN7Pa474 DMSO). Data are presented as mean ± SD, °°°/***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "CLN7: 256471"
  },
  {
    "caption": "(A) Representative  confocal images  and Quantification of STX  within the  lysosome  in U2-OS  and HeLa  cells after acute silencing of CLN3 (siCLN3) in  DMSO  or treated 48h with Tamoxifen. (*** vs siSCR DMSO, °°° vs siCLN3 DMSO). Data are presented as mean ± SD, °°°/***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "CLN3: 1201"
  },
  {
    "caption": "(B) Representative  confocal image and quantification of Gb3 in ARPE-19 CLN3 KO cells silenced with siRNA against scramble sequence and TFEB (siTFEB) for 72h and treated for the last 48h with DMSO or  Tamoxifen. Data are presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "CLN3: 1201
TFEB: 7942"
  },
  {
    "caption": "(C) Representative confocal image and quantification of TFEB  in U2-OS cells silenced with siRNA against scramble sequence and CLN3  (siCLN3) for 72h and treated for the last 48h with DMSO or Tamoxifen (5 µM and 10 µM). Data are presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "CLN3: 1201"
  },
  {
    "caption": "(C) Representative confocal image and quantification of TFEB localization in HeLa TFEB-GFP transfected with RagC for 48h and treated for the last 3h with DMSO, Torin1, Tamoxifen  or Ospemifene. Ratios of nuclear to  cytosolic TFEB localization in RagC non-expressing (RagC-) and RagC-expressing cells (RagC+) are presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "GFP: 
RagC: 64121
TFEB: 7942"
  },
  {
    "caption": "D) Representative confocal images and quantification of STX in ARPE-19 CLN3 KO cells transfected with empty vector or HA-RagC for 48h and treated for 48h with DMSO or Tamoxifen. STX average spot area presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (n=3 biological replicas in duplicate). Scale bars: 20 µm.",
    "ncbi_link": "HA: 
CLN3: 1201
RagC: 64121"
  },
  {
    "caption": "Representative confocal images of STX  in the  Cortex, Hippocampus, and Cerebellum brain  section derived from 7.5 months-old mouse  WT or CLN7Δex2 injected with vehicle or Tamoxifen (Tamox). Quantification of confocal images, the plot shows the quantification of the STX  average spot area normalized for the number of Hoechst positive cells. (*** vs WT, °°°/°° vs CLN7Δex2 Vehicle). Data are presented as mean ± SD, **/oo: P ≤ 0.001, ***/ooo: P ≤ 0.0001, as determined by ANOVA (N≥3 biological replicas). Scale bars: 60 µm.",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "Representative  confocal images  of SCMAS in the Cortex, Hippocampus, and Cerebellum brain  section derived from mouse  WT or CLN7Δex2 injected with vehicle or Tamoxifen. Quantification of  confocal images, the plot shows the quantification of the SCMAS average spot area normalized for the number of  Hoechst  positive cells. (*** vs WT, °°° vs CLN7Δex2 Vehicle). Data are presented as mean ± SD, ***: P ≤ 0.0001, as determined by ANOVA (N≥3 biological). Scale bars: 60 µm.",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "(A-B) Representative confocal images  and quantification of  IBA-1  in the  Cortex, Hippocampus, and Cerebellum brain  section derived from WT or CLN7Δex2 mice injected with the vehicle or Tamoxifen. (***/**/* vs WT, °°°/°°/° vs CLN7Δex2 Vehicle). Data are presented as mean ± SD, */o: P ≤ 0.01, **/oo: P ≤ 0.001, ***: P ≤ 0.0001, as determined by ANOVA (N≥3 biological replicas). Scale bars: 50 µm.",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "(D) Representative Images of  hindlimb clasping test in mouse WT or CLN7Δex2 injected with vehicle or Tamoxifen.",
    "ncbi_link": "CLN7: 72175"
  },
  {
    "caption": "F. Dopaminergic neuronal cultures from control lines and glucocerebrosidase (GBA) N370S PD patients were immunoblotted for the presence of LAG3. No band for LAG3 could be observed in neurons.",
    "ncbi_link": "GBA: 2629
glucocerebrosidase: 2629"
  },
  {
    "caption": "G. Using high power, high resolution laser scanning confocal microscopy, no human LAG3 signal could be detected in human neurons (Auto-hLAG3 transduced, DOX OFF) by two different anti-human LAG3 antibodies (17B4 and D2G40; left panel and zoomed-in insets) whereas LAG3 was clearly detected in human neurons induced to express hLAG3 (DOX ON; right panel and zoomed-in insets). Scale bars 25 µm.",
    "ncbi_link": "LAG3: 3902"
  },
  {
    "caption": "D. Using high power, high resolution laser scanning confocal microscopy, no mouse LAG3 signal could be detected in murine primary neuronal cultures (Auto-mLAG3 transduced, DOX OFF and non-transduced neurons) using anti-mouse LAG3 antibody (MABF954) whereas LAG3 was clearly detected in primary neurons induced to express mLAG3 (Auto-mLAG3 transduced, DOX ON). Scale bars 20 µm.",
    "ncbi_link": "LAG3: 16768"
  },
  {
    "caption": "E. RT-qPCR-derived CT values to measure the cDNA copy number. Mixed neuroglial cultures, glial cultures, and neuron-enriched cultures show transcript levels that are close to indistinguishable to those from LAG3‑/‑ BH. Conversely, around 1600 transcripts/ng of RNA were counted in activated T cells.",
    "ncbi_link": "LAG3: 3902"
  },
  {
    "caption": "Human neural cultures transduced by Auto-hLAG3 were treated by α-synuclein PFFs 4 days post LAG3 expression induction by DOX and kept in culture for 2 or 4 weeks. Both transgenic (hLAG3 D2G40-positive in (A) and 17B4-positive in (B)) and non-transduced, wild-type neurons (selected neurons in zoomed-in insets) propagated α-synuclein and developed characteristic pS129-positive (81A-positive in (A) and EP1536Y-positive in (B)) α-synuclein aggregates. Scale bars 25 µm. Trained ilastik algorithms were used to segment pixels of 81A, EP1536Y and MAP2 stainings imaged by high-content wide-field microscope, which were used to quantify the signal of 81A-positive (C) and EP1536Y-positive (D) α-synuclein aggregates expressed as % of MAP2-positive area. Almost the entire wells (182 fields per well) were imaged for every condition and replicate and each datapoint in the plot represents the entire well. Error bars indicate mean ± SD of biological replicates (duplicates). For few conditions, unicates were used, shown as one dot. One-way ANOVA followed by Tukey's multiple comparison test demonstrated that neurons that did not express LAG3 (DOX OFF) showed no difference in α-synuclein propagation when compared to LAG3-expressing neurons (DOX ON) as demonstrated by two different pS129 α-synuclein antibodies (p=0.9998 for 81A at 2 weeks and p=0.2522 at 4 weeks; p=0.9986 for EP1536Y at 2 weeks and p=0.3042 at 4 weeks).",
    "ncbi_link": "LAG3: 3902"
  },
  {
    "caption": "A. Survival curves of A53T α-synuclein TG mice, with LAG3 knockout, heterozygous LAG3 expression, or LAG3 WT. Median survival was shortest for α-synuclein TG LAG3‑/‑ at 239 d, followed by α-synuclein TG LAG3+/- at 260 d and α-synuclein TG LAG3+/+ at 268 d. The survivals of ASYNA53T LAG3‑/‑, LAG3+/- and LAG3+/+ mice were similar (Mantel-Cox log-rank test, p-value = 0.165). Mice were euthanized and dissected in the late-stage symptomatic phase, which would inevitably result in death within a week. None of the control LAG3‑/‑ α-synuclein WT mice died over the course of the experiment.",
    "ncbi_link": "LAG3: 16768
α-synuclein: 6622
α-synuclein: 20617"
  },
  {
    "caption": "C. Immunofluorescence staining and quantification of pS129-positive α-synuclein inclusions in hippocampal slice cultures (HSCs) at 5 weeks post-seeding with 350 µM PFF. Scale bars represent 500 µm (overview), and 100 µm (insets). Shown is mean ± SEM and individual values are shown; n = 6 cultures per group; two-way-ANOVA revealed for LAG3 F(1, 20) = 0.0294; p = 0.8656; A53T F(1, 20) = 36.42, p < 0.0001; interaction F(1, 20) = 0.0062, p = 0.9382. Bonferroni's correction for multiple comparisons revealed p = 0.9973 for LAG3 WT vs. KO in A53T TG and p > 0.9808 for LAG3 WT vs. KO in A53T WT.",
    "ncbi_link": "LAG3: 16768"
  },
  {
    "caption": " C. STING-KO or sgRNA control (Ctrl) MC38 cells were treated in vitro with the indicated concentrations of 5-FU. Cell viability were determined using the CellTiter-Glo assay after two days, with normalized luminescence levels shown. N=3. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " Mice were injected with Ctrl or STING-KO MC38 cells, and treated with PBS or 5-FU. (D) Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": "  Mice were injected with Ctrl or STING-KO MC38 cells, and treated with PBS or 5-FU. (E) Tumor volumes were quantified at the indicated days post cancer cell injection. N=4 to N=5 as shown in (D).  ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " Mice were injected with Ctrl or STING-KO MC38 cells, and treated with PBS or 5-FU. (F) Tumor and spleen weights at the endpoint for (E), with each dot representing a mouse. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " WT MC38 cells were injected into STING+/+ or STING-/- mice, and treated with 5-FU or PBS following the schematics in (A). (G) Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": "  WT MC38 cells were injected into STING+/+ or STING-/- mice, and treated with 5-FU or PBS following the schematics in (A). (H) Tumor volumes were quantified at the indicated days post cancer cell injection. N=5.  ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " WT MC38 cells were injected into STING+/+ or STING-/- mice, and treated with 5-FU or PBS following the schematics in (A). (I) Tumor and spleen weights at the endpoint for (H), with each dot representing a mouse. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " B. Western blot for Ctrl and STING KO YUMM1.7 cells, assayed with STING and Gapdh antibodies. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " C. STING-KO or sgRNA control (Ctrl) YUMM1.7 cells were treated in vitro with the indicated concentrations of DTIC. Cell viability were determined using the CellTiter-Glo assay after two days, with relative cell viability shown. N=3. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " YUMM1.7 Ctrl or STING KO cells were injected into mice. 5-FU and DTIC responses were followed according to the schematics in (A). (E) Representative images of tumors and spleens. Image panels were cropped from the same picture. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " YUMM1.7 Ctrl or STING KO cells were injected into mice. 5-FU and DTIC responses were followed according to the schematics in (A). (F) Mean tumor volumes of Ctrl or STING KO YUMM1.7 with DMSO, DTIC or 5-FU treatment were followed during the experiment. N=3 to N=5, as shown in (E). ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " YUMM1.7 Ctrl or STING KO cells were injected into mice. 5-FU and DTIC responses were followed according to the schematics in (A). (G) Tumor (left panel) and spleen (right panel) weights were determined at the endpoint for the experiment followed in (F). Each dot represents data from a mouse. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " A. Control (Ctrl) or STING-KO MC38 cells were treated in vitro with STING agonist cGAMP (left) for 6 hours or 5-FU (right) or relevant vehicle controls for 24 hours. The expression of indicated genes was determined by qRT-PCR. N=3. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " B. Ctrl or STING-KO CT26 cells were treated with 5-FU or vehicle control for 24 hours. The RNA expression levels of indicated genes were determined by qRT-PCR. N=3. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " C. Ctrl or STING-KO YUMM1.7 cells were treated with (left panel) vehicle control (DMSO) or DTIC, or (right panel) PBS or 5-FU for 24 hours. The expression of indicated genes was determined by qRT-PCR. N=3. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " D. Western blot analysis was performed with Ifnα and Gapdh antibodies, for control (Ctrl) and Ifna1-Ifnb1-double-KO (Ifn-DKO) MC38 cells. Two independent KO clones are shown. ",
    "ncbi_link": "Ifna1: 15962
Ifnb1: 15977"
  },
  {
    "caption": " A. Western blot for control sgRNA (Ctrl) and cGAS-KO MC38 cells, assayed with cGAS and Gapdh antibodies. ",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": " Mice were injected with Ctrl or cGAS-KO MC38 cells and treated with PBS or 5-FU. (B) Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture. ",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": " Mice were injected with Ctrl or cGAS-KO MC38 cells and treated with PBS or 5-FU. (C) Tumor volumes were quantified at the indicated days post cancer cell injection. N=4 to N=5, as shown in (B). ",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": " Mice were injected with Ctrl or cGAS-KO MC38 cells and treated with PBS or 5-FU. (D) Tumor and spleen weights at the endpoint for (C), with each dot representing a mouse. ",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": " A. Western blot for Ctrl and Ifnar1-KO MC38 cells, analyzed with Ifnar1 and Gapdh antibodies. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " B. Ctrl or Ifnar1-KO MC38 cells were treated with PBS or recombinant Ifnβ for 4 hours. The RNA expression levels of indicated ISGs were analyzed using qRT-PCR. N=3. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or Ifnar1-KO MC38 cells, and treated with 5-FU or PBS. (C) Pictures of tumors and spleens from a representative experiment. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or Ifnar1-KO MC38 cells, and treated with 5-FU or PBS. (D) Tumor volumes were quantified at the indicated days post cancer cell injection. N=5. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or Ifnar1-KO MC38 cells, and treated with 5-FU or PBS. (E) Tumor and spleen weights at the endpoint for (D), with each dot representing a mouse. Ctrl tumor data in (C-E) are the same as those in Figure 4B-4D. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "  experiment to test the function of Ifnar1 in bone marrow (BM) derived cells. WT C57BL/6 mice were transplanted with either Ifnar1+/+ or Ifnar1-/- BM cells. Recipient mice were allowed to recover followed by the injection of WT MC38 cells, before treatment with 5-FU or PBS. (G) Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture. ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "
 experiment to test the function of Ifnar1 in bone marrow (BM) derived cells. WT C57BL/6 mice were transplanted with either Ifnar1+/+ or Ifnar1-/- BM cells. Recipient mice were allowed to recover followed by the injection of WT MC38 cells, before treatment with 5-FU or PBS. (H) Tumor volumes were quantified at the indicated days post cancer cell injection. N=4 to N=5, as shown in (G). 
",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "
 experiment to test the function of Ifnar1 in bone marrow (BM) derived cells. WT C57BL/6 mice were transplanted with either Ifnar1+/+ or Ifnar1-/- BM cells. Recipient mice were allowed to recover followed by the injection of WT MC38 cells, before treatment with 5-FU or PBS. (I) Tumor and spleen weights at the endpoint for (H), with each dot representing a mouse. 
",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or STING-KO MC38 cells and treated with PBS or 5-FU. Tumors were harvested 2 weeks after cancer cell injection and intratumoral immune cells were examined by flow cytometry. A. The counts of CD45+ cells per gram of tumor. B. The percentages of CD45+ cells among forward scatter (FSC) and side scatter (SSC) gated live cell population. C. The counts of CD3+, CD3-NK1.1+, CD3-CD19+, CD11b+ and CD11c+CD103+ cells per gram of tumor were quantified. D. The percentages of CD3+, CD3-NK1.1+, CD3-CD19+, CD11b+ and CD11c+CD103+ cells among CD45+ cells were quantified. E. The counts of CD4+ and CD8+ T cells per gram of tumor. F. The percentages of CD4+ and CD8+ cells among CD3+ T cells were quantified. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or STING-KO MC38 cells, and subjected to treatments, with each dose consisting of 25 mg/kg, 50 mg/kg or 75 mg/kg 5-FU, or PBS. A. Pictures of tumors and spleens from a representative experiment. Image panels were cropped from the same picture. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or STING-KO MC38 cells, and subjected to treatments, with each dose consisting of 25 mg/kg, 50 mg/kg or 75 mg/kg 5-FU, or PBS. B. Tumor volumes were quantified at the indicated days post cancer cell injection. N=5. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " Mice were injected with control (Ctrl) or STING-KO MC38 cells, and subjected to treatments, with each dose consisting of 25 mg/kg, 50 mg/kg or 75 mg/kg 5-FU, or PBS. C. Tumor and spleen weights at the endpoint for (B), with each dot representing a mouse. ",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": " B. STING RNA expression from the same 58 specimens were partitioned into STING-Low (bottom 15 samples) and STING-Hi (top 43 samples) groups. Kaplan Meier curve is shown with P value indicated. ",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": " C. Stage II and Stage III patients from the TCGA COAD dataset were partitioned into STING-Hi (top 1/3 of samples, N=87) and STING-Low (bottom 1/3 of samples, N=87). Kaplan Meier curve is shown with P value indicated. ",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "D. From a published colorectal cancer chemotherapy response study, STING RNA expression in responders and non-responders were compared, with each dot representing a tumor.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "C Comparison of 3H-serine incorporation in ApoE ACM-treated WT- and Mfn2-KO MEFs (mean±SE; n=3, with 3 replicates/experiment).",
    "ncbi_link": "ApoE: 348
Mfn2: 170731"
  },
  {
    "caption": "D Duramycin sensitivity in ApoE ACM-treated fibroblasts. Note increased sensitivity after 20 min to 5 μM duramycin in ApoE4-treated cells, which was blocked upon the addition of 15 μM exogenous PtdEtn (mean±SD; n=3, with 3 replicates/experiment).",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "B Fractions from the discontinuous gradient were blotted with anti-ApoE (WUE-4) antibody; the doublet is a characteristic feature on ApoE western blots due to ApoE sialylation [16].",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "C An ApoE-containing fraction (fraction 5 [+]), an ApoE-negative fraction (fraction 3 [-]), and recombinant lipid-free ApoE protein were applied to human fibroblasts. Note increase in phospholipid synthesis using an ApoE4-containing lipoprotein fraction, but not with either an ApoE4-negative fraction or with lipoprotein-free recombinant ApoE3 or ApoE4 protein (mean ± SE; n=3, with 3 replicates/experiment).",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "A Cholesteryl ester synthesis, as measured by 3H-oleate incorporation. Note increased CE in ApoE4-treated cells, whereas there was essentially no difference in triglyceride (TAG) production (mean±SE; n=3. with 3 replicates/experiment). †, p=0.06 vs E3.",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "B Comparison of 3H-oleate incorporation in ApoE ACM-treated WT- and Mfn2-KO MEFs (mean±SE; n=3, with 5 replicates/experiment).",
    "ncbi_link": "ApoE: 348
Mfn2: 170731"
  },
  {
    "caption": "C ApoE ACM-treated fibroblasts were stained with LipidTox green neutral lipid stain, and lipid droplets were visualized (example at left) and counted (right). Note significantly more lipid droplets in ApoE4-treated cells (mean ± SD, n=3).",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "HeLa cells were transfected with plasmids to visualize ER (in green) and mitochondria (in red), and then were treated with ApoE3- and ApoE4-ACM for 24 hours. Shown is a box-and-whisker plot comparing co-localization in ApoE3 ACM (n = 15 images analyzed [gray circles, average of co-localization in ~5 cells in each image field]) compared to that in ApoE4 ACM (n = 18 images).",
    "ncbi_link": "ApoE: 348"
  },
  {
    "caption": "(A) SDS-PAGE gels stained with coomassie showing the purity of the Chlamydomonas IFT-B2 components, over-expressed in E. coli or insect cells, after the last purification step by SEC. IFT54/20 and IFT57/38 were purified as hetero-dimeric complexes whereas IFT80, IFT172 and an N-terminal IFT172(1-968) (IFT172ΔC) constructs were purified as single components. A cartoon representation of the predicted domain architecture of IFT-B2 components using HHPRED (Söding et al, 2005) is shown at the center.",
    "ncbi_link": "IFT172: 5717250"
  },
  {
    "caption": "(B)Pull-down analysis for the hexameric IFT-B2 complex. A mixture of IFT172ΔC, IFT80, and the IFT57/38 complex ('input') shows only weak non-specific binding to GSH-resin ('empty'), but all proteins are pulled down by IFT54/20-GST complex. Note that the IFT20-GST and IFT38 proteins co-migrate on the gel and cannot be properly resolved. However, the presence of the IFT57 protein in the pull-down sample implies that its binding partner IFT38 is also there.",
    "ncbi_link": "IFT172: 5717250"
  },
  {
    "caption": "(A-C) SEC elution profiles and corresponding SDS PAGE gels of IFT172ΔC, IFT57/38, IFT80, IFT54/20 as well as mixtures of IFT172ΔC/57/38, IFT80/57/38 and IFT172ΔC/80/57/38 demonstrating that IFT57/38 associates with both IFT80 and IFT172ΔC. Only the central peak fraction from each SEC experiment is shown on the SDS PAGE gel. Note that the presence of both IFT172ΔC and IFT80 in a single peak in (c) (peak 3) is due to the fact that these two proteins elute in the same position, and not because they physically interact (see also Appendix Fig. S2B).",
    "ncbi_link": "IFT172: 5717250"
  },
  {
    "caption": "(D) GSH resin pull-down of a mixture of IFT80 and IFT172ΔC (input, lane 1) with GST-tagged CH-domains of IFT57 or IFT38 (IFT57CH or IFT38CH) or with the GST-tagged coiled-coil (CC) region of IFT57 mixed with His-tagged coiled-coil region of IFT38. The SDS-PAGE gel shows interaction between IFT57CH-IFT172ΔC, IFT38CH-IFT80 and IFT57CC-IFT38CC.",
    "ncbi_link": "IFT38: 5722691
IFT172: Q5DM57///5717250
IFT57: 5724201"
  },
  {
    "caption": "(A) Coomassie-stained SDS-PAGE gel showing GST-pulldown experiments between the IFT-B2 complex and an IFT88/52N subcomplex. The pre-assembled IFT-B2 complex (lane 1) shows no non-specific interaction with empty GSH-beads (lane 2), but is efficiently pulled down by IFT88/52N-GST (with an IFT52(1-335) construct comprising the N-terminal domain as well as the IFT88-binding region) (lane 3). Both IFT88 and IFT52N are required for the interaction with IFT-B2 because neither the N-terminal IFT52 domain (residues 1-275; lane 4) alone, nor an IFT88/52 complex lacking the N-terminal IFT52 domain (with an IFT52(281-335) construct containing only the IFT88-binding region) (lane 5) show efficient pull-down of IFT-B2. Contaminants from the purification of the complex shown in lane 5 are marked with asterisks.",
    "ncbi_link": "IFT52: 5717848
IFT88: 5725696"
  },
  {
    "caption": "Bioluminescence imaging and quantification of brain metastases (H) of BALB/c nude mice xenografted with control or IFITM1-knockout H1299 cells (populations of knockout cells) by intracardiac injection (1×106 cells). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) (H, quantification of brain metastases",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "Bioluminescence imaging overall survival (I) of BALB/c nude mice xenografted with control or IFITM1-knockout H1299 cells (populations of knockout cells) by intracardiac injection (1×106 cells). #, experimental endpoint (I). , the log-rank test (I, survival",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(J) Bioluminescence imaging and quantification of brain metastases and overall survivals of BALB/c nude mice xenografted with control or IFITM1-overexpressing H460 cells by intracardiac injection (1×105 cells). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) the log-rank test survival in J",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(N) Kaplan-Meier survival curves of lung cancer patients in the TCGA dataset (n=415) stratified by IFITM1 mRNA expression. HR, hazard ratio. the log-rank test survival in N)",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(A) Representative immunofluorescence images and quantification of microglial (TMEM119+) or macrophage (TMEM119-/F4/80+) density per microscopic field in the brain on day 1 or 7 after the intracardiac injection of control or IFITM1-overexpressing LLC-BrM cells (tdTomato, 1×106) into C57BL/6 mice (90, 90, and 120 fields for normal, day 1, and day 7, respectively; normal, 3 mice; day 1, 3 mice; day 7, 4 mice). Normal brain tissue was used as the control.",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(C) Flow cytometric analysis of violet-labeled LLC-BrM cells phagocytosed by microglia in the brains of LLC-BrM cell-allografted BALB/c nude mice on day 1 after intracardiac injection (1×106 control or IFITM1-knockout cells). Representative flow cytometry pseudocolor density plots and the gating strategy are shown, and the bar graph shows the percentage of violet+ microglia. (The n-values denote the number of mice per group.)",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(E) LLC-BrM cells (tdTomato) were surrounded by activated microglia (Iba1+, green) and IFNγ (white) in the brain on day 1 or 7 after intracardiac injection of control or IFITM1-overexpressing cells (1×106) into C57BL/6 mice. IFNγ intensities in the fields enclosed in the yellow dotted lines (ROIs) (90, 90, and 120 fields for normal, day 1, and day 7, respectively) are shown. The ROI was set as the entire area of the metastatic lesion for day 7 and as the area of single metastatic cell for day 1. ImageJ was used to quantify the immunofluorescence intensity in the ROI. Normal brain tissue was used as the control. ROI, region of interest.",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(G) Results of ELISA for mouse IFNγ in the brain on day 1 after the intracardiac injection of control or IFITM1-knockout LLC-BrM cells (1×106) into BALB/c nude mice. PLX5622 (1,200 PPM) was administered in chow from day -3 to day 1. BLZ945 (200 mg/kg) was administered by oral gavage from day -2 to day 1. Minocycline (33 mg/kg) was administered intraperitoneally on days -1, 0, and 1. Clodronate liposomes (100 μl/10 g) were administered intraperitoneally on day -1. Normal brain tissue was used as the control. (The n-values denote the number of mice per group.)",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(E) ELISA results of mouse IFNγ in the brain on day 1 after intracardiac injection of the indicated LLC-BrM cells (control, C3 knockout, IFITM1 overexpression, or IFITM1 overexpression in combination with C3 knockout, 1×106) into C57BL/6 mice. Normal brain tissue was used as the control. (The n-values denote the number of mice per group.)",
    "ncbi_link": "C3: 12266
IFITM1: 68713"
  },
  {
    "caption": "(G) Control and IFITM1-overexpressing LLC-BrM cells (1×106, tdTomato) were surrounded by activated microglia (left, green, Iba1+) and complement C3 (left, white) in the brain on day 1 after intracardiac injection into C57BL/6 mice (normal, 3 mice; day 1, 3 mice; day 7, 4 mice). Complement C3 intensities in the fields enclosed in the yellow dotted lines (ROIs) are shown (right; 90, 90, and 120 fields for normal, day 1, and day 7, respectively). The ROI was set as the area of a single metastatic cell. ImageJ was used to quantify the immunofluorescence intensity in the ROI. Normal brain tissue was used as the control. ROI, region of interest.",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "We would like to point out that TNFα, instead of IFNγ, was used as a marker of microglial activation in vitro (H) Results of ELISA for mouse TNFα in the culture supernatant of primary mouse microglia (6×104, from 16 C57BL/6 mice), primary mouse BMDMs (6×104, from 3 C57BL/6 mice), or primary mouse BrM-BMDMs (6×104, from 37 C57BL/6 mice) stimulated with conditioned medium from control LLC-BrM cells (1×104) and IFITM1-knockout LLC-BrM cells (1×104). BMDMs, primary bone marrow-derived macrophages. BrM-BMDMs, primary bone marrow-derived macrophages from the brain metastatic lesions of LLC-BrM cell-isografted C57BL/6 mice on day 20 after the intracardiac injection of LLC-BrM cells (1×105 cells). CM, conditioned medium (3 independent experiments).",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(L) Flow cytometric analysis of apoptotic LLC-BrM cells (6×104) in contact coculture with primary mouse microglia (6×104, from 16 C57BL/6 mice), which were activated by conditioned medium from control or C3-knockdown H460 cells (1×106). CM, conditioned medium (3 independent experiments).",
    "ncbi_link": "C3: 718"
  },
  {
    "caption": "(A) Schematic of efficacy of adoptive CD8+ T cell immunotherapy in suppressing brain metastasis (top far left), representative western blots of IFITM1 expression in control or IFITM1-overexpressing LLC-BrM cells (bottom far left), bioluminescence imaging (middle left), quantification of brain metastases (middle right) and overall survivals (far right) of BALB/c nude mice allografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (1×105 cells). Primary mouse naïve CD8+ T cells from 12 C57BL/6 mice or not were injected intravenously on days -1, 6, and 13 (1×104 cells at each time point). (The n-values denote the number of mice per group, and 4 independent Western blot experiments were performed.) (B) Schematic of efficacy of adoptive CD8+ or CD4+ T cell immunotherapy in suppressing brain metastasis (far left), bioluminescence imaging (middle left), quantification of brain metastases (middle right) and overall survivals (far right) of BALB/c nude mice allografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (1×105 cells). Primary mouse naïve CD8+ or CD4+ T cells from 12 C57BL/6 mice were injected intravenously on days -1, 6, and 13 (1×104 cells at each time point). (The n-values denote the number of mice per group.) (quantification of brain metastases ANOVA with uncorrected Fisher's LSD test or the log-rank test (survival",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(G) Bioluminescence imaging and quantification of brain metastases on day 20 in C57BL/6 mice isografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (3×105 cells). Mice were systemically primed-boosted with homologous LLC-BrM cell lysates (1×106 cells for day -21 and 1×105 cells for day -7) before injection of cancer cells. Then, IgG or an anti-CD8α antibody (2 μg/mouse) was injected intravenously on day 3 alone or in combination with minocycline treatment (33 mg/kg) on day 1. Minocycline was administered intraperitoneally. (The n-values denote the number of mice per group.) one-way (G)",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(I) Immunoblot analysis of MHC-I expression in the cytoplasm, on the cell membrane, and in the nucleus of control and IFITM1-overexpressing H1299 cells (6×104) (3 independent experiments).",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(K) qPCR analysis of MHC-I mRNA expression in control and IFITM1-overexpressing H1299 cells (6×104) with or without IFNγ stimulation (1,000 U/ml) for 24 hr (3 independent experiments). (L) qPCR analysis of MHC-I mRNA expression in control and IFITM1-knockdown H1299 cells (6×104) with or without IFNγ stimulation (1,000 U/ml) for 24 hr (3 independent experiments).",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(M) Cleaved caspase 3 (green)-positive LLC-BrM cells (tdTomato) were surrounded by CD8+ T cells (white) in the brain metastatic lesions of LLC-BrM cell-isografted C57BL/6 mice on day 20 after intracardiac injection of control or IFITM1-overexpressing LLC-BrM cells (1×106 cells). The positively stained areas of single CD8+ T cells, clustered CD8+ T cells, cleaved caspase 3+ cancer cells, and tdTomato+ cancer cells in the ROI were calculated by ImageJ. The ratios of the areas between the clustered and single CD8+ T cells are shown as the numbers of CD8+ T cells in the ROI, and the ratios of the areas between cleaved caspase 3+ cancer cells and tdTomato+ cancer cells are shown as the percentages of cleaved caspase 3+ cancer cells in the ROI (90 fields per group, 3 mice per group). Yellow dotted lines (ROIs), brain metastatic lesions; ROI, region of interest.",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(O) Kaplan-Meier survival curves of lung cancer patients in the TCGA dataset stratified by IFITM1 and MHC-I mRNA expression. HR, hazard ratio. ANOVA with uncorrected Fisher's LSD test, or the log-rank test (O).",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "(F) Bioluminescence imaging, quantification of brain metastases, and overall survival of C57BL/6 mice isografted with control or IFITM1-overexpressing LLC-BrM cells by intracardiac injection (3×105 cells). Mice were systemically primed-boosted with homologous LLC-BrM cell lysates (1×106 cells for day -21 and 1×105 cells for day -7) before injection of cancer cells, and IgG or an anti-PD-1 antibody (100 μg/mouse) was then injected intravenously on days 3, 6, and 9. (The n-values denote the number of mice per group.) unpaired two-way (quantification of brain metastases in F) ANOVA with uncorrected Fisher's LSD test, or the log-rank test (survival in F).",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "(H) Bioluminescence imaging and quantification of brain metastases in C57BL/6 mice isografted with control or IFITM1-knockout LLC-BrM cells by intracardiac injection (3×105 cells). IgG (30 μg/mouse, days 3, 6, and 9), an anti-PD-1 antibody (30 μg/mouse, days 3, 6, and 9), or UV-irradiated oncolytic virus (106 pfu/mouse, days 0, 2, and 4) was injected intravenously alone or in combination as indicated. (The n-values denote the number of mice per group.) one-way (quantification of brain metastases in H)",
    "ncbi_link": "IFITM1: 68713"
  },
  {
    "caption": "C Superposition of 3D volumes of full‐length human TFG and truncated TFG (amino acids 1‐193). The truncated form is depicted in yellow, while the full‐length form is depicted as gray mesh. The top view (top) exhibits limited differences in the structures, while the side view (bottom) shows extra density in the full‐length TFG isoform. Scale bar, 25 Å.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A Cells depleted of endogenous TFG were transfected with a variety of TFG transgenes (including full‐length, untagged TFG, a truncation mutant encoding amino acids 1‐300 of untagged TFG, and a truncation mutant encoding amino acids 1‐350 of untagged TFG) and stained using α‐TFG and α‐Sec31A antibodies. Scale bar, 5 μm. Inset scale bar, 1 μm. Images shown are representative of at least 15 individual cells analyzed for each condition.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "C, D Control cells (C) or cells depleted of endogenous TFG (D) were transfected with a construct expressing TFG with a carboxyl‐terminal GFP tag and stained using α‐Sec31A antibodies. Scale bar, 5 μm. Images shown are representative of at least 20 individual cells analyzed for each condition.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A HumanRPE‐1 cells were mock‐transfected (control) or transfected with a TFG siRNA for 60 h. Cells were fixed and stained using α‐Sec16A and α‐Sec31A antibodies and imaged using confocal microscopy. Images shown are projections of 3D data sets (4 μm in z). Both individual and merged images with Sec16A in green and Sec31A in red are shown (at least 15 cells for each condition). Scale bar, 5 μm. Higher magnification views of the indicated regions (boxed) are also shown in the lower or upper right portion of each image. Inset scale bar, 1 μm.B Quantification of the number of Sec31A‐labeled structures in a 4 μm2 region. For both conditions (control or TFG siRNA‐treated), at least 50 distinct regions away from the peri‐nuclear Golgi were examined. Error bars represent mean ± SEM; at least 15 different cells per condition. **P 0.01 compared with control, calculated using a paired t‐test.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "C Quantification of the number of Sec16A‐labeled structures in a 4 μm2 region. For both conditions (control or TFG siRNA‐treated), at least 50 distinct regions away from the peri‐nuclear Golgi were examined. Error bars represent mean ± SEM; at least 15 different cells per condition. No statistically significant difference was observed, following analysis using a paired t‐test.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "D Cells stably expressing low levels of GFP‐ERGIC‐53 and mRuby‐Sec23A were fixed and imaged using SR‐SIM (top), or depleted of endogenous TFG prior to fixation and SR‐SIM imaging (bottom). Images shown are representative of at least 15 individual cells analyzed for each condition. Scale bar, 5 μm. Inset scale bar, 1 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "E HumanRPE‐1 cells were mock‐transfected (control) or transfected with a TFG siRNA for 60 h. Cells were fixed and stained using α‐Sec16A and α‐ERGIC‐53 antibodies and imaged using SR‐SIM. Images shown are projections of 3D data sets (4 μm in z). Both individual and merged images with Sec16A in green and ERGIC‐53 in red are shown (at least 15 cells for each condition). Scale bar, 5 μm. Higher magnification views of the indicated regions (boxed) are also shown in the lower or upper right portion of each image. Arrowheads highlight Sec16A‐labeled structures that do not exhibit juxtaposed ERGIC‐53 staining. Inset scale bar, 1 μm.F Based on structured illumination microscopy, quantification of the number of Sec16A‐labeled structures juxtaposed (within 500 nm) to ERGIC‐53‐labeled structures is shown. For both conditions (control or TFG siRNA‐treated), at least 1,000 unique Sec16A‐labeled structures were examined. Error bars represent mean ± SEM; at least 15 different cells per condition. **P 0.01 compared with control, calculated using a paired t‐test.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A HumanRPE‐1 cells stably expressing low levels of mannosidase II‐mApple (ManII‐mApple) were mock‐transfected (control) or transfected with a TFG siRNA for 60 h, then fixed and stained using TFG antibodies and imaged using confocal microscopy. Alternatively, cells were either treated with DMSO (top row) or brefeldin A (BFA) for 1 h (middle row), followed by fixation, or washed into fresh media following DMSO or BFA treatment for 30 min (bottom row), prior to fixation. Images shown are projections of 3D data sets (4 μm in z). Merged images with TFG in green and ManII in red are shown. Scale bar, 5 μm. Images shown are representative of at least 10 individual cells analyzed for each condition.B Human RPE‐1 cells were mock‐transfected (control) or transfected with a TFG siRNA for 60 h, then fixed and stained using TFG and GM130 antibodies and imaged using confocal microscopy. Alternatively, cells were either treated with DMSO (top row) or brefeldin A (BFA) for 1 h (middle row), followed by fixation, or washed into fresh media following DMSO or BFA treatment for 30 min (bottom row), prior to fixation. Images shown are projections of 3D data sets (4 μm in z). Merged images with TFG in green and GM130 in red are shown. Scale bar, 5 μm. Images shown are representative of at least 10 individual cells analyzed for each condition.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A HumanRPE‐1 cells stably expressing low levels of mannosidase II‐mApple were transfected with a TFG siRNA for 60 h. Cells were subsequently treated with brefeldin A (BFA) for 1 h, followed by a wash into fresh media and further incubation for 2 h in the absence of BFA, prior to fixation. Images shown are projections of 3D data sets (4 μm in z). Merged images with Sec31A in green and ManII in red are shown (representative of at least 15 cells analyzed). Scale bar, 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "B HumanRPE‐1 cells stably expressing low levels of mannosidase II‐mApple were transfected with a TFG siRNA for 60 h. Cells were subsequently treated with BFA for 1 h, followed by a wash into fresh media and further incubation for 1 h in the absence of BFA, prior to fixation and staining using α‐Sec16A and α‐Sec31A antibodies. Images shown are projections of 3D data sets (4 μm in z). Merged images with Sec31A (green), ManII (red), and Sec16A (blue) are shown (representative of at least 15 cells analyzed). Scale bar, 5 μm.C Higher magnification views of the indicated regions in (B, boxed) are shown. Arrows highlight COPII‐positive transport carriers that contain the cargo ManII, which are not juxtaposed to Sec16A‐labeled sites on the ER. Additionally, arrowheads point out distinct foci in which COPII continues to associate with Sec16A‐labeled sites, indicating that COPII vesicle formation continues in the absence of TFG. Scale bar, 1 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "E. As in (D), except that cells were treated with Cisplatin for 24 h (mean±SEM; n=3 independent experiments). F. U2OS WT, U2OS/SCAI KO and U2OS/SCAI KO/Strep-HA-SCAI cells were treated or not with MMC (9 nM) for 48 h, fixed and co-stained with PCNA antibody and DAPI. Cell cycle distribution was analyzed by quantitative image-based cytometry (QIBC) (≥2000 cells analyzed per condition). Data from a representative experiment are shown.",
    "ncbi_link": "HA: 
SCAI: 286205"
  },
  {
    "caption": "G. U2OS WT, U2OS/SCAI KO and U2OS/SCAI KO/Strep-HA-SCAI cells were treated or not with MMC (90 nM) for 1 h, fixed 24 h later and co-stained with RPA2 antibody and DAPI. RPA2 foci were quantified by QIBC (≥3000 cells analyzed per condition; mean±SD; n=3 independent experiments; *, p<0.05; ns, not significant, two-tailed paired t-test). H. As in (G), except that cells were co-stained with γH2AX antibody and DAPI (≥3000 cells analyzed per condition; mean± SD; n=3 independent experiments; *, p<0.05; **, p<0.01; ns, not significant, two-tailed paired t-test).",
    "ncbi_link": "HA: 
SCAI: 286205"
  },
  {
    "caption": "F. U2OS and U2OS/SCAI KO cells transfected with indicated siRNAs for 48 h were treated or not with MMC (90 nM) for 1 h, fixed 24 h later and co-stained with RPA2 antibody and DAPI. RPA2 foci were quantified by QIBC (≥3000 cells analyzed per condition; mean±SD; n=3 independent experiments; *, p<0.05; ns, not significant, two-tailed paired t-test). G. As in (F), except that cells were stained with γH2AX antibody (≥3000 cells analyzed per condition; mean±SD; n=3 independent experiments; **, p<0.01; ns, not significant, two-tailed paired t-test).",
    "ncbi_link": "SCAI: 286205"
  },
  {
    "caption": "I. Clonogenic survival of U2OS and U2OS/FANCA KO cells subjected to indicated doses of MMC for 24 h (mean±SEM; n=3 independent experiments). J. Clonogenic survival of U2OS, U2OS/SCAI KO, U2OS/FANCA KO, and U2OS/FANCA+SCAI DKO cells subjected to indicated doses of MMC for 24 h (mean±SEM; n=3 independent experiments).",
    "ncbi_link": "FANCA: 2175
SCAI: 286205"
  },
  {
    "caption": "K. Immunoblot analysis of U2OS, U2OS/SCAI KO, U2OS/FANCA KO, and U2OS/FANCA SCAI DKO cell lines exposed or not to MMC as indicated.",
    "ncbi_link": "FANCA: 2175
SCAI: 286205"
  },
  {
    "caption": "F. pICLpt was replicated in mock- or SCAI-depleted egg extract in the presence of [α-32P]dATP for the indicated times, and reactions were analyzed by native agarose gel electrophoresis. ∆SCAI-C and ∆SCAI-N denote SCAI immunodepletion with an antibody raised against the C- or N-terminus of SCAI, respectively; RI, replication intermediates; OC, open circular; SC, supercoiled.",
    "ncbi_link": "SCAI: 108700016"
  },
  {
    "caption": "D. GFP IPs from U2OS or U2OS/GFP-SCAI cells transfected with indicated siRNAs were immunoblotted with indicated antibodies. Note that a small fraction of REV7 is still immunoprecipitated with GFP-SCAI in REV3 knockdown cells. This could be due to incomplete knockdown, and/or additional interactions of SCAI with the REV1-Polζ complex that are independent of REV3.",
    "ncbi_link": "GFP: 
REV1: 51455
REV3: 5980
SCAI: 286205"
  },
  {
    "caption": "E. Representative images of metaphase spreads from U2OS/SCAI KO cells transfected with indicated siRNAs and processed as in Figure 1I. Scale bars, 10 µm.",
    "ncbi_link": "SCAI: 286205"
  },
  {
    "caption": "H. Clonogenic survival of U2OS and U2OS/SCAI KO cells transfected with non-targeting control (CTRL) or Polθ siRNAs and subjected to indicated doses of MMC for 24 h (mean±SEM; n=3 independent experiments).",
    "ncbi_link": "Polθ: 10721
SCAI: 286205"
  },
  {
    "caption": "A.  Fura2 340/380  time traces from M-CSF-differentiated macrophages derived from conditionally-immortalised  macrophage precursor cell lines (M-MØP) of Plcg2P522 mice (P522, blue) and Plcg2R522 mice (R522, red). One set of cell lines, generated from male mice, is shown. Cells were exposed to 5µg/ml anti-FcγRII/III along with 20µM EGTA  and 2µM Ionomycin as indicated. Data shows the mean±SD of 3 independent experiments analysed by two-way ANOVA with Sidak post-hoc tests (** = p<0.01; **** = p< 0.0001). B. Fura2 340/380 time traces from primary  microglia derived from the cortex  of Plcg2R522 mice (blue: P522) and Plcg2R522 mice (red: R522) with or without pre-exposure for 2 hours with  Edelfosine (10µM). Cells were exposed to 5µg/ml anti-FcγRII/III along with EGTA and 2µM  Ionomycin. Data shows the mean±SD of 3 independent experiments analysed by two-way ANOVA with Sidak post-hoc tests (** = p<0.01; *** = p<0.001; **** = p< 0.0001). C ",
    "ncbi_link": "Plcg2: 234779"
  },
  {
    "caption": "B) Comparison of mRNA levels of Nrg3, Nrg1β type III (Nrg1β−III), Nrg2β, Nrg1β type II (Nrg1β−II), Nrg2α and Nrg1β type I (Nrg1β−I) in the cortex (Cx), hippocampus (HC) and striatum (Str) of juvenile mice (P30-60) by quantitative RT-PCR. Data represent means ± SD of 4 biological replicates. 2-way-ANOVA with Bonferroni's multiple comparisons test was performed to assess statistical significance (****P<0.0001, ***P<0.001, ns=not significant).",
    "ncbi_link": "Nrg1β: 211323
Nrg2α: 100042150
Nrg2β: 100042150
Nrg3: 18183"
  },
  {
    "caption": "E, F) Immunohistochemical analysis in the hippocampus of wildtype (E,E',E'') and ErbB4 mutant mice (F) at 2 month of age using Nrg3-, ErbB4- and parvalbumin (Parv)-specific antibodies. The white box in (E) is displayed magnified in (E',E''). In control mice, Nrg3 is enriched on dendrites of ErbB4+ PV interneurons, compared to the surrounding neuropil (E',E''). In ErbB4 mutants, the Nrg3 enrichment on PV interneurons is not apparent (F).",
    "ncbi_link": "ErbB4: 13869"
  },
  {
    "caption": "H) Quantification of GluA4 puncta present on ErbB4+ dendrites in the CA1 stratum radiatum of adult wildtype (wt) and Nrg3-/- mice (age P90-120). Data are presented as box plots with Tukey's whiskers and outliers; means are indicated by a Plus symbols. n=65 (wt) and n=62 (Nrg3-/-) from 5 animals each. Unpaired t-test (2-tailed) with Welch's correction was performed to assess statistical significance (****P<0.0001).",
    "ncbi_link": "Nrg3: 18183"
  },
  {
    "caption": " C, D) Neurons from Nrg3-/-;ErbB4-/-;vGAT-Cre mice were transduced with a lentivirus expressing either (C) ErbB4wt or (D) ErbB4kd (kinase dead ErbB4) in a Cre-dependent manner, and with a second virus at a low titer expressing Nrg3/SypCFP. Immunocytochemical analysis of ErbB4 and SypCFP; (C,C') and (D,D') each show the same image, (C',D') show the SypCFP signal ",
    "ncbi_link": "Cre: 
ErbB4: 13869
Nrg3: 18183
vGAT: 22348"
  },
  {
    "caption": " E-G) Quantification of Synapse preference towards ErbB4+ neurons (E), ErbB4 enrichment (F) and SypCFP enrichment (G) in synapses on neurons expressing wildtype ErbB4 (wt) or  ErbB4kd (kd) ",
    "ncbi_link": "ErbB4: 13869"
  },
  {
    "caption": " H) Nrg3-/- neuron cultures were transfected with a plasmid that strongly overexpresses Nrg3 and GFP and immunostained with antibodies against ErbB4, GFP and GluA; (H) shows the triple stained image, while (H') and (H'') only show ErbB4 and GluA signals, respectively ",
    "ncbi_link": "Nrg3: 18183"
  },
  {
    "caption": " I) Co-cultures of Nrg3-/- neurons with HEK293 cells expressing Nrg3. Cultures were stained with antibodies against Nrg3, ErbB4 and GluA. Note that Nrg3, ErbB4 and GluA are enriched at the contact sites between Nrg3-expressing HEK293 cells and ErbB4+ neurons ",
    "ncbi_link": "Nrg3: 18183"
  },
  {
    "caption": "(C) Selected stills from live imaging analysis of mitotic progression in neuroblasts expressing UASPoloWT or UASPoloT182D under the control of inscuteable-Gal4 driver. Neuroblasts without Polo overexpression were used as control. Mitotic progression was followed in vivo by direct visualization of tubulin-RFP and the centromere marker CID-GFP. Time 0 refers to nuclear envelope breakdown (NEBD). (D) Quantification of the mitotic time (from NEBD to anaphase onset) for neuroblasts shown in (C). NEBD was identified as the time tubulin entered the nuclear space and anaphase onset as the time sister KTs separated (n≥12 neuroblasts for each condition, n≥3 independent experiments) (E) Quantification of the time spent in prometaphase (from NEBD until last KT alignment at the metaphase plate) for neuroblasts shown in (C) (n≥11 neuroblasts for each condition, n≥3 independent experiments). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: ns, not significant; *<0.05; **<0.01; ****<0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "Gal4: 855828
inscuteable: 37355
Polo: 40232"
  },
  {
    "caption": "(F) Measurement of inter-kinetochore distance during mitotic progression for neuroblasts shown in (C). Only KT pairs within the maximum of two consecutive z-planes were considered eligible for quantification. Images were acquired every 20 sec. The graph shows the mean distance between two CID centroids in a KT pair over time (t=0 is NEBD). A linear regression was applied to the data set. Vertical dashed lines highlight the time at which cells overexpressing PoloWT (gray) or PoloT182D (red) reach the average inter-kinetochore distance measured in metaphase cells without Polo overexpression (black) (n≥7 neuroblasts for each condition). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: ns, not significant; *<0.05; **<0.01; ****<0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(G) Selected stills from live imaging of neuroblasts expressing Mad2-GFP to follow KT-MT attachment status upon expression of PoloWT or PoloT182D. CID-RFP was used as KT reference. Insets show magnifications of the outlined regions showing single KT pairs that take longer to align at the metaphase plate. Asterisks indicate direction of chromosome segregation (putative spindle pole positions). (H) Graph represents the mean fluorescence intensity (MFI) for Mad2-GFP at KTs measured from NEBD to anaphase onset for neuroblasts shown in (G). Each line represents the average of all KTs measured from a single neuroblast at each time point. Mad2-GFP MFI was determined relative to CID-RFP MFI (n≥16 neuroblasts for each condition, n=5 independent experiments).Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: ns, not significant; *<0.05; **<0.01; ****<0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(A) Representative immunofluorescence images of KT alignment efficiency in mitotic S2 cells expressing PoloWT-EGFP, PoloT182D-EGFP or lacking expression of any Polo transgene. Cells were treated with MG132 prior to fixation to prevent cells from exiting mitosis and increase the number of pre-anaphase figures. Insets display magnifications of the outlined regions, which highlight both low-tension misaligned (inset 1 and 2) and high-tension aligned KTs (inset 3). (B) Graph represents the percentage of cells in each indicated mitotic state, as shown in (A) (n≥ 532 cells for each condition, n=2 independent experiments). Data information: Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(C) Representative immunofluorescence images of calcium-stable KT-MT attachments in metaphase S2 cells expressing either PoloWT-EGFP or PoloT182D-EGFP. Insets display magnifications of the outlined regions. Asterisk highlights either an aligned KT pair attached to MTs in an end-on fashion (PoloWT-EGFP) or an aligned KT pair in which a sister KT is laterally attached to the end of a MT fiber (PoloT182D-EGFP). Plotted profiles show the overlap between Polo-EGFP and tubulin signals for the highlighted KT. (D) Graph represents the percentage of metaphase cells showing at least 1 KT with a lateral interaction, as shown in (C) (asterisk) (n≥58 cells for each condition, n=2 independent experiments). Data information: Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(E) Selected frames from live image analysis of chromosome segregation fidelity in neuroblasts expressing either PoloWT or PoloT182D. Neuroblasts without Polo overexpression were used as control. Jupiter-GFP was imaged for direct visualization of the mitotic spindle. Time 0 refers to anaphase onset.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(B) Representative images of the eye phenotype observed in adult flies that were expressing UASPoloT182D in the eye imaginal disc during development at indicated temperatures. An example of an eye from an adult fly co-expressing UASPoloT182D with UASRodRNAi is also shown. Expression of UASlacZ transgene in the eye imaginal disc was used as control for overexpression and UAS dilution effect.",
    "ncbi_link": "lacZ: 
Polo: 40232
Rod: 43719"
  },
  {
    "caption": "(C) Graph represents the mean percentage of males born at 25°C either expressing eyGal4-driven UASPoloT182D together with UASlacZ or in combination with UASRodRNAi (n≥3 independent crosses for each condition). The number of males with the genotype of interest born in each cross was normalized to the mean total number of males that are born in a control cross (eyGal4>UASlacZ, n=9 independent crosses). Data information: Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "lacZ: 
ey: 43812
Gal4: 855828
Polo: 40232
Rod: 43719"
  },
  {
    "caption": "(D) Selected stills from live cell imaging of neuroblasts expressing either UASPoloT182D alone or in Rod-depleted background (UASPoloT182D+UASRodRNAi). Neuroblasts without transgene expression were used as control and neuroblasts expressing UASPoloT182D together with UASlacZ were used as control for UAS dilution effect. (E) Quantification of the time spent in prometaphase (from NEBD until last KT alignment at the metaphase plate) for neuroblasts shown in (D) (n≥17 neuroblasts for each condition, n≥4 independent experiments). Statistical analysis was calculated using an one-way ANOVA test for multiple comparisons. p values: ns, not significant; **, <0.01. Data information: Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "lacZ: 
Polo: 40232
Rod: 43719"
  },
  {
    "caption": "(A) Selected stills from live cell imaging of neuroblasts expressing UASPoloWT, UASPoloT182D, or depleted of dynein heavy chain (UASDhcRNAi) and expressing Rod-GFP under control of its endogenous promoter. CID-RFP was used as a KT reference. Insets display magnifications of the outlined regions, which highlight late congressing KTs. Asterisks indicate direction of chromosome segregation (putative spindle pole positions). (B) Graph represents the mean fluorescence intensity (MFI) for Rod-GFP determined relative to CID-RFP MFI for the KT pairs highlighted in (A). Time was measured from the first frame a KT pair moved away from the other congressing KTs, until metaphase alignment (vertical dashed lines). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: **, <0.01; ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "Dhc: 38580
dynein heavy chain: 38580
Polo: 40232"
  },
  {
    "caption": "(C) Graph represents the levels of KT Rod-GFP determined relative to CID-RFP measured throughout mitotic progression for control neuroblasts (UASPoloWT, n= 24 neuroblasts, n=4 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: **, <0.01; ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(E) Selected stills from live imaging analysis of Rod-GFP streaming from KTs in neuroblasts expressing either PoloWT or PoloT182D. Asterisks indicate direction of chromosome segregation (putative spindle poles positions). Arrowheads highlight streaming of Rod-GFP from unaligned KTs. Representative kymographs are shown for Rod-GFP streaming from metaphase until anaphase onset (AO). Frames were acquired every 5sec. Data information: Scale bar: 5 μm.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(A) Representative immunofluorescence images of ZW10 levels at unaligned KTs in neuroblasts expressing UASPoloWT, UASPoloT182D or depleted of dynactin subunit p50 (UASp50RNAi) or Spindly (UASSpindlyRNAi). Spc105 was used as a KT reference. Insets display magnifications of the outlined regions which highlight both late congressing KT (inset 1) and sister KTs that are non-oriented along the spindle axis (inset 2, except for the UASPoloWT panel which displays congressed KTs). UASPoloWT neuroblasts were used as control. Data information: Scale bar: 5 μm.",
    "ncbi_link": "dynactin subunit p50: 44086
p50: 44086
Polo: 40232
Spindly: 33578"
  },
  {
    "caption": "(C) Selected stills from live imaging analysis of KT alignment in neuroblasts expressing UASPoloT182D, either alone or in a Rod-depleted background (UASPoloT182D+UASRodRNAi), depleted of dynactin (UASp50RNAi), Spindly (UASSpindlyRNAi), dynein (UASDhcRNAi) or Rod in a dynein-depleted background (UASDhcRNAi+UASRodRNAi). Outlined regions show KTs that are non-oriented (lateral attachment) relative to spindle axis and that were followed over time until stable biorientation (arrowhead). Cartoon depicts the behavior of the respective KT pair over successive frames relative to the spindle axis (dashed lines). Neuroblasts without transgene expression were used as control. Data information: Scale bar: 5 μm.",
    "ncbi_link": "dynactin: 44086
p50: 44086
Dhc: 38580
dynein: 38580
Polo: 40232
Rod: 43719
Spindly: 33578"
  },
  {
    "caption": "(A) Representative immunofluorescence images of Spindly localization to unaligned KTs in Drosophila S2 cells expressing either PoloWT-EGFP or PoloT182D-EGFP. Insets display magnifications of the outlined regions. Cells were treated with MG132 prior to fixation to increase the number of late prometaphase figures and allow better identification of late congressing KTs. CID was used as a KT reference. (B) Graph represents the percentage of Spindly levels at late congressing and non-oriented (not oriented parallel to the spindle axis) KTs for cells shown in (A). Spindly levels were determined relative to CID and all values were normalized to the mean fluorescence intensity quantified in cells expressing PoloWT-EGFP, which was set to 100% (n≥121 KTs from at least 39 cells for each condition, n=3 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(C) Selected frames from live imaging analysis of SpindlyWT-EGFP behavior during KT alignment in Drosophila S2 cells expressing either PoloWT-mRFP or PoloT182D-mRFP. Insets show magnifications of the outlined regions that highlight KTs with delayed congression to the spindle equator (yellow dashed line). Time 0 is the first shift in KT direction from poleward to anti-poleward movement. (D) Graph represents the variation in SpindlyWT-EGFP levels at KTs highlighted in (C) and its correlation with efficiency of alignment. Spindly-EGFP mean fluorescence intensity (MFI) levels were corrected for photobleaching during acquisition and normalized to the first frame of analysis to account for differences in expression levels. KTs were tracked during the process of congression (using Polo-mRFP signal as a KT reference) and the distance from the unaligned KT pair to the spindle equator was measured. All values were normalized to the last frame of analysis (stable integration in metaphase plate). Time 0 is the first shift in KT direction from poleward to anti-poleward movement (n≥9 KTs from at least 5 cells for each condition, n≥4 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
mRFP: 
Polo: 40232
Spindly: 33578"
  },
  {
    "caption": "(E) Representative immunofluorescence images of Spindly accumulation at aligned KTs in Drosophila S2 cells expressing either PoloWT-EGFP or PoloT182D-EGFP, in control or upon depletion of dynein heavy chain. Insets display magnifications of the outlined regions. CID was used as a KT reference. Data information: Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
dynein: 38580
Polo: 40232"
  },
  {
    "caption": "(F) Representative immunofluorescence images of Spindly accumulation at unattached KTs in Drosophila S2 cells expressing either PoloWT-EGFP or PoloT182D-EGFP. Insets display magnifications of the outlined regions. Cells were treated with colchicine prior to fixation to generate unattached KTs. CID was used as a KT reference. Data information: Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(G) Graph represents Spindly levels at aligned KTs for cells Spindly levels were determined relative to CID and all values were normalized to the mean fluorescence intensity quantified in control PoloWT-EGFP expressing cells, which was set to 100% (n≥633 KTs from at least 35 cells for each condition, n=2 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(H) Graph represents Spindly levels at unattached KTs for cells Spindly levels were determined relative to CID and all values were normalized to the mean fluorescence intensity quantified in PoloWT-EGFP expressing cells, which was set to 100% (n≥1282 KTs from at least 59 cells for each condition, n=2 independent experiments). Data information: Statistical analysis was calculated using an unpaired t-test (Mann-Whitney). p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm. ",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(D) Representative immunofluorescence images of Spindly-phospho(ph)Ser499 levels at unattached KTs in control Drosophila S2 cells and in Polo-depleted or BI2536-treated cells. Insets display magnifications of the outlined regions. Cells were treated with colchicine prior to fixation to generate unattached KTs. CID was used as a KT reference. Data information: Scale bar: 5 μm.",
    "ncbi_link": "Polo: 40232"
  },
  {
    "caption": "(F) Representative immunofluorescence images of Spindly phS499 levels at unaligned and aligned KTs in a PoloWT-EGFP expressing Drosophila S2 cell. Insets show magnifications of the outlined regions, which highlight either a unaligned (u) KT or an aligned (a) KT. CID was used as a KT reference. Plotted profiles of signal intensities of phS499 and CID are shown for the highlighted KTs. Data information: Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Polo: 40232"
  },
  {
    "caption": "(D) Selected frames from live imaging analysis of SpindlyS499A-EGFP or SpindlyS499D-EGFP behavior during KT alignment in Drosophila S2 cells expressing PoloWT-mRFP. SpindlyWT-EGFP expressing cells were used as control. All Spindly-EGFP constructs were resistant to the RNAi targeted against endogenous Spindly. Insets show magnifications of the outlined regions that highlight KTs that delay in congressing to the spindle equator (yellow dashed line). Time 0 is the first shift in KT direction from poleward to anti-poleward movement. (E) Graph represents the variation in SpindlyWT-EGFP, SpindlyS499A-EGFP and SpindlyS499D-EGFP levels at KTs highlighted in (D) and its correlation with efficiency of alignment. All values were determined as described in Fig.6D. Time 0 is the first shift in KT direction from poleward to anti-poleward movement (n≥5 KTs from at least 4 cells for each condition, n≥2 independent experiments). Data information: XXXX Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
mRFP: 
Polo: 40232
Spindly: 33578"
  },
  {
    "caption": "(A) Representative immunofluorescence images of ZW10 localization to unaligned KTs in Drosophila S2 cells expressing either SpindlyWT-, SpindlyS499A- or SpindlyS499D-EGFP. Insets display magnifications of the outlined regions, which highlight late congressing KTs. CID was used as a KT reference. (B) Graph represents the percentage of ZW10 levels at late congressing and non-oriented (not oriented parallel to the spindle axis) KTs for cells shown in (A). ZW10 levels were determined relative to CID and all values were normalized to the control mean fluorescence intensity, which was set to 100% (n≥72 KTs from at least 26 cells for each condition, n=4 independent experiments). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: *, <0.05; **, <0.01; ****, <0.0001 . Data are shown as mean ±SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Spindly: 33578
ZW10: 47874"
  },
  {
    "caption": "(C) Selected frames from live imaging analysis of chromosome congression in Drosophila S2 cells expressing SpindlyWT-EGFP, SpindlyS499A-EGFP, SpindlyS499D-EGFP or SpindlyS499D-EGFP in a ZW10-depleted background. The first frame shows EGFP-positive cells. Chromosome alignment was followed in vivo by direct visualization of KT-associated PoloWT-mRFP signal. Time 0 refers to nuclear envelope breakdown (NEBD), metaphase refers to full KT alignment and Anaphase onset refers to onset of chromosome segregation. (D) Quantification of the time spent in prometaphase (from NEBD until last KT alignment at the metaphase plate) for cells shown in (C) (n≥10 cells for each condition, n≥2 independent experiments). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: *, <0.05; **, <0.01; ****, <0.0001 . Data are shown as mean ±SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Spindly: 33578
ZW10: 47874"
  },
  {
    "caption": "(A) Representative immunofluorescence images of ZW10 streaming from KTs in Drosophila S2 cells in metaphase expressing either SpindlyWT-, SpindlyS499A- or SpindlyS499D-EGFP. ZW10 streaming is also shown in S2 cells expressing SpindlyWT- or SpindlyS499A-EGFP in a dynein-depleted background. Insets display magnifications of the outlined regions, which highlight streaming robustness. (B) Graph represents the percentage of cells in metaphase showing different levels of ZW10 streaming (n≥35 cells for each condition, n=2 independent experiments). (C) Graph represents the percentage of ZW10 levels at aligned KTs normalized to ZW10 levels at the spindle region. All values were normalized to the mean fluorescence intensity quantified in SpindlyWT-EGFP expressing cells, which was set to 100% (n≥470 KTs from at least 35 cells for each condition, n=2 independent experiments). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
dynein: 38580
Spindly: 33578"
  },
  {
    "caption": "(D) Representative immunofluorescence images of calcium-stable KT-MT attachments in metaphase S2 cells expressing SpindlyWT-, SpindlyS499A-, SpindlyS499D- or SpindlyS499D-EGFP in a ZW10-depleted background. Insets display magnifications of the outlined regions which highlight different attachment configurations (E - end on; L - lateral; M - merotelic). Cartoon depicts the attachment configuration of the respective KT pair. Asterisk highlights an aligned KT pair in which a sister KT appears to be laterally attached to the end of a MT fiber. Plotted profiles show the overlap between CENP-C and tubulin signals for the highlighted KT. CENP-C was used as a KT reference. (E) Graph represents the percentage of metaphase cells showing only end-on attachments or at least 1 KT with lateral or merotelic attachment, as shown in D (n≥44 cells for each condition, n≥2 independent experiments). Data information: Statistical analysis was calculated using a Kruskal-Wallis test for multiple comparisons. p values: ****, <0.0001. Data are shown as mean ± SD. Scale bar: 5 μm.",
    "ncbi_link": "EGFP: 
Spindly: 33578
ZW10: 47874"
  },
  {
    "caption": "Statistical analysis of stx mutant stx34 sleep profile compared with that of the Canton-S control. 24-hour-sleep curve (y-axis was average sleep time in every 30 minutes), n=16. Statistical analysis of stx mutant stxd77 sleep profile compared with control w1118. 24-hour-sleep curve, n=16.",
    "ncbi_link": "stx: 32005"
  },
  {
    "caption": "Rescue experiment of stx mutant. The stx mutant phenotype can be rescued by stx over expression driven by stx-Gal4 (in female flies, P) or EB1-Gal4 (Q). For P, from left to right females mean±SEM: 226.0±11.76, n=49; 336.6±14.10, n=86; 382.7±16.43, n=50; 357.8±16.55, n=72; 296.2±16.04, n=68; 484.9±12.97, n=49; 507.6±13.83, n=86; 539.5±12.99, n=50. 577.0±11.34, n=72; 520.7±14.96, n=68; For Q, from left to right mean±SEM; 398.3±9.535, n=63; 378.4±23.78, n=32; 324.4±12.33, n=45; 495.8±16.43, n=28; 478.5±14.65, n=53; 328.7±16.99, n=34; 540.7±7.690, n=63; 489.9±21.39, n=32; 490.9±13.65, n=45; 494.7±11.99, n=28; 537.8±12.07, n=53; 450.3±15.47, n=34.",
    "ncbi_link": "EB1: 35584
Gal4: 855828
stx: 32005"
  },
  {
    "caption": "Statistical analysis of Pc and stx double mutant stxd77;; pcXT109 sleep profile compared with controls. Quantitative RT-PCR of Octβ2R in adult head of stxd77 and w1118 control. (Data represent mean±SEM: w1118, 0.8853±0.1177; N=3; stxd77/Y, 0.3263±0.1575；N=3).",
    "ncbi_link": "Octβ2R: 41549
stx: 32005"
  },
  {
    "caption": "Rescue of stxd77 by over expressing Octβ2R in ellipsoid body. From left to right mean±SEM: 399.6±11.49, n=50; 400.3±10.48, n=60; 349.9±14.77, n=48; 495.8±16.43, n=28; 470.1±13.04, n=44; 423.6±14.32, n=47; 548.6±8.707, n=50; 499.0±8.225, n=60; 490.7±16.26, n=48; 494.7±11.99, n=28; 480.2±14.64, n=44; 437.4±14.85, n=47.",
    "ncbi_link": "Octβ2R: 41549
stx: 32005"
  },
  {
    "caption": "Rescue of stxd77 by Pc RNAi in ellipsoid body. From left to right mean±SEM: 399.9±11.88, n=48; 409.8±11.50, n=49; 348.7±20.19, n=32; 495.8±16.43, n=28; 459.3±14.78, n=61; 407.5±15.66, n=40; 550.7±8.881, n=48; 516.0±11.76, n=49; 502.3±15.08, n=32; 494.7±11.99, n=28; 546.3±11.35, n=61; 514.2±18.94, n=40. Note that the same data is used for genotype stxd77;; EB1-Gal4 in panel F and G.",
    "ncbi_link": "EB1: 35584
Gal4: 855828
Pc: 40358
stx: 32005"
  },
  {
    "caption": "Quantitative RT-PCR of stx after OA treatment in w1118 control and Octβ1R, Octβ2R mutants, Octβ3R mutants. (From left to right mean±SEM: 1.000±0.0288, 0.781±0.0176, 1.477±0.043，1.403±0.0578, 1.157±0.0617, 0.881±0.0689, 1.149±0.0398, 0.953±0.0543, 1.017±0.0600, 1.090±0.0378, N=3).",
    "ncbi_link": "Octβ1R: 42652
Octβ2R: 41549
Octβ3R: 3885573
stx: 32005"
  },
  {
    "caption": "Ellipsoid body knock down of Octβ2R results in sleep rebound increase. In response to OA, ellipsoid knock down of Octβ2R rescues control phenotype. Data represent mean±SEM: 13.80±2.439, n=31; 5.465±2.036, n=25; 19.55±2.275, n=27; 12.47±2.684, n=24; 30.03±3.428, n=25; 43.67±4.616, n=25.",
    "ncbi_link": "Octβ2R: 41549"
  },
  {
    "caption": "Sleep profile of PcXT109 mutant with or without OA treatment. In both control and PcXT109 mutant flies, the treatment of OA results in sleep decrease, n=16 (G). Quantifications of the decreasing amount showed that PcXT109 mutant fly loss significantly more sleep that control flies (From left to right mean±SEM: 13.90±1.397; 21.25±1.493, N=4) (H).",
    "ncbi_link": "Pc: 40358"
  },
  {
    "caption": "Total sleep for Tβh mutant and control flies in video-based method (From left to right mean±SEM: 688.2±32.71, n=48; 123.2±11.68, n=46).",
    "ncbi_link": "Tβh: 31718"
  },
  {
    "caption": "B-D'') Representative images showing that Hh accumulates on the surface of LDs in glial cells of the CB (yellow arrows) Glial cells are marked by repo-GAL4>GFP and CB is circled in (B).",
    "ncbi_link": "GFP: 
GAL4: 855828
repo: 47285"
  },
  {
    "caption": "K-L'') Hh-LD associations are observed in the cortex glia (yellow arrows, NP2222-GAL4>mGFP).",
    "ncbi_link": "mGFP: 
NP2222: 
GAL4: 855828"
  },
  {
    "caption": "A-D) Representative images showing that upon knockdown of Hh in cortex glial cells (NP2222-GAL4>mGFP with UAS-dcr2), cortex glial membrane and overall Repo+ glial cell number are significantly reduced, quantified in (C) (n=7, 8 brain lobes) and (D) (n=7, 8 brain lobes), respectively. E-G) Hh knockdown in glia (repo-GAL4>GFP) results in niche disruption and clustering of NBs (circled with yellow dashed line), as well as an increase in the percentage of NBs in M phase (pH3+), quantified in (E) (n=12, 10 brain lobes). ",
    "ncbi_link": "mGFP: 
GFP: 
NP2222: 
dcr2: 36993
GAL4: 855828
Hh: 42737
repo: 47285"
  },
  {
    "caption": "H-K) Representative images showing that Hh overexpression using pan-glial (repo-GAL4) and cortex-glial (NP2222-GAL4) drivers both result in a decrease in NB EdU index, quantified in (J) (n=16, 20 brain lobes) and (K) (n=11, 14 brain lobes), respectively.",
    "ncbi_link": "GAL4: 855828
Hh: 42737
repo: 47285"
  },
  {
    "caption": "L-M'') Representative images showing ci-lacZ is expressed in NBs (yellow arrows). (M-M'') are zoomed in images of (L).",
    "ncbi_link": "lacZ: 
ci: 43767"
  },
  {
    "caption": "N-P) Overexpression of ciACT in NBs (dnab-GAL4) reduces EdU index, quantified in (P) (n=12, 10 brain lobes).",
    "ncbi_link": "ci: 43767
GAL4: 855828
dnab: 3346237"
  },
  {
    "caption": "E-G) Lsd-2 knockdown in cortex glial cells (NP2222-GAL4) where hh is overexpressed effectively reduces LD number in CB (outlined in yellow dashed lines). H-K) Representative images showing that NB EdU index is rescued upon Lsd-2 knockdown in cortex glial cells (NP2222-GAL4) where hh is overexpressed, quantified in (K) (n=11, 14; 16, 14; 6, 14 brain lobes). The NP2222-GAL4>w1118 vs hhOE columns depict the same data as Fig 2K. EdU+ NBs are circled with yellow, dashed lines. ",
    "ncbi_link": "NP2222: 
GAL4: 855828
hh: 42737
Lsd-2: 32437"
  },
  {
    "caption": "A-D') Representative images showing that pan-glial overexpression of htlACT, but not InRwt or EgfrACT causes an expansion of cortex glia that enwraps NBs. Glial cells are marked with repo-GAL4 >GFP, and NBs are marked with Mira. (A', B', C' and D') are zoomed in images of (A, B, C and D), respectively.",
    "ncbi_link": "GFP: 
Egfr: 37455
GAL4: 855828
htl: 42160
InR: 42549
repo: 47285"
  },
  {
    "caption": "Representative images showing that cortex glial overexpression of htlACT but not InRwt or EgfrACT causes an increase in cortex glial membrane size (H) (n=10, 10 brain lobes) NP2222-GAL4>mGFP is used to mark cortex glial membrane in (E-G)",
    "ncbi_link": "mGFP: 
NP2222: 
Egfr: 37455
GAL4: 855828
htl: 42160
InR: 42549"
  },
  {
    "caption": "Representative images showing that cortex glial overexpression of EgfrACT to mark cortex glial membrane wrapper-GAL4> is used in (I, J).",
    "ncbi_link": "Egfr: 37455
GAL4: 855828
wrapper: 37555"
  },
  {
    "caption": "cortex glial overexpression of htlACT but not InRwt or EgfrACT causes an increase in glial cell (Repo+) numbers quantified in (K) (n=10, 10, 10; 7, 12 brain lobes)",
    "ncbi_link": "Egfr: 37455
htl: 42160
InR: 42549
Repo: 47285"
  },
  {
    "caption": "L) Glial (repo-GAL4>) overexpression of InRwt but not htlACT or EgfrACT significantly reduces the number of CB NBs (n= 10, 10, 8, 11 brain lobes).",
    "ncbi_link": "Egfr: 37455
GAL4: 855828
htl: 42160
InR: 42549
repo: 47285"
  },
  {
    "caption": "M) Glial (repo-GAL4>) overexpression of htlACT but not InRwt or EgfrACT significantly reduces the pH3 index of CB NBs",
    "ncbi_link": "Egfr: 37455
GAL4: 855828
htl: 42160
InR: 42549
repo: 47285"
  },
  {
    "caption": "A-E) Representative images showing that both pan-glial (repo-GAL4>) and cortex glial (NP2222-GAL4>) htlACT overexpression significantly reduce NB EdU index, quantified in (E) (n=15 ,14; 10, 16 brain lobes). (A, B, C, D) are single sections with Mira and EdU staining, and (A', B' C', D') are Z-projection of the EdU staining.",
    "ncbi_link": "NP2222: 
GAL4: 855828
htl: 42160
repo: 47285"
  },
  {
    "caption": "pan-glial (repo-GAL4) htlACT overexpression lengthens NB cell cycle, quantified in (F) The cell cycle length is measured as the length between consecutive divisions.",
    "ncbi_link": "GAL4: 855828
htl: 42160
repo: 47285"
  },
  {
    "caption": "Representative still images from ex vivo CNS live imaging at 72ALH showing that pan-glial (repo-GAL4) htlACT overexpression lengthens NB cell cycle, (n= 25, 6 NBs imaged from 3 brains per genotype). NBs (Dpn::GFP, red; Histone RFP, grey) are circled with blue dashed lines.",
    "ncbi_link": "GAL4: 855828
htl: 42160
repo: 47285"
  },
  {
    "caption": "M-O) Representative images showing that the number of EdU+ neurons generated per NB is significantly reduced upon pan-glial overexpression of FGF (repo-LexA > LexAop-htlACT; yellow arrows), quantified in (O) n= 94, 127 NB lineages imaged from 5 and 7 brain lobes, respectively). NB lineages are marked with dnab-gal4 > GFP.",
    "ncbi_link": "FGF: 
GFP: 
LexA: 
gal4: 855828
htl: 42160
dnab: 3346237
repo: 47285"
  },
  {
    "caption": "A) Pan-glial (repo-GAL4) htlACT overexpression causes upregulation of hh, fasn1 and lsd2 transcripts (n = 3 biological replicates pooled from 20 brains for each genotype; for each biological replicate, we ran 3 technical replicates for each PCR reaction). The lipogenesis genes (acc, lipin), and lipolysis gene bmm transcripts are not significantly altered. We utilised rpl32 as a reference gene in these experiments, as it is not altered by htlACT overexpression. The data are represented by log2 fold change relative to the control (repo-GAL4> w1118).",
    "ncbi_link": "rpl32: 
acc: 35761
bmm: 39611
fasn1: 33524
GAL4: 855828
hh: 42737
htl: 42160
lipin: 35790
lsd2: 32437
repo: 47285"
  },
  {
    "caption": "C-G) Representative images showing that Hh staining normally localised to a ring like structure (yellow arrows), becomes delocalises to the glial cytoplasm upon htlACT overexpression, quantified in (E) (n=4, 6 brain lobes). Glial cells are marked with repo-GAL4>GFP. (E-F') are zoomed in images of (C-D').",
    "ncbi_link": "GFP.: 
GAL4: 855828
htl: 42160
repo: 47285"
  },
  {
    "caption": "H) Cortex glial (NP2222-GAL4>) overexpression of two independent hh RNAis significantly rescue EdU incorporation defects caused by htlACT overexpression (n=10, 16; 7, 12; 14, 11 brain lobes).",
    "ncbi_link": "NP2222: 
GAL4: 855828
hh: 42737
htl: 42160"
  },
  {
    "caption": "I) Knockdown of NB Hh signalling pathway (dnab-GAL4> UAS-ciRNAi) rescues NB EdU incorporation defects induced by glial htlACT overexpression (repo-LexA> LexAop-htlACT). Induction of ciRNAi in NBs alone increases NB EdU incorporation (n=8, 13; 10, 10; 30, 26; 12, 7 brain lobes).",
    "ncbi_link": "LexA: 
ci: 43767
GAL4: 855828
htl: 42160
dnab: 3346237
repo: 47285"
  },
  {
    "caption": "J) The NB EdU incorporation defects due to cortex glial (NP2222-GAL4>) overexpression of htlACT, is significantly rescued by overexpression of RNAis against fasn1 and lsd2, compared to corresponding control RNAis (n=10, 16; 25, 17; 14, 8 brain lobes).",
    "ncbi_link": "NP2222: 
fasn1: 33524
GAL4: 855828
htl: 42160
lsd2: 32437"
  },
  {
    "caption": "B) Inhibition of palmitoylation (via two independent rasp RNAis) rescues NB EdU incorporation defects induced by cortex glial (NP2222-GAL4>) htlACT overexpression, while knockdown of Rasp in cortex glial cells alone does not alter NB EdU index (n=10, 15; 10, 16; 18, 21; 26, 29 brain lobes).",
    "ncbi_link": "NP2222: 
GAL4: 855828
htl: 42160
rasp: 44098
Rasp: 44098"
  },
  {
    "caption": "C-C') Representative images showing that Hh.N.EGFP (which cannot undergo cholesterol modification) are found as puncta on the surface of NBs (yellow arrows) when overexpressed in neighbouring cortex glial cells (NP2222-GAL4>).",
    "ncbi_link": "NP2222: 
GAL4: 855828"
  },
  {
    "caption": "Representative images showing that knockdown of Fasn1 in glial cells (repo-GAL4>), where Hh.N.EGFP is overexpressed, significantly reduces the number of Hh.N.EGFP puncta on the surface of NBs (yellow arrows) n=38, 38, 57 NBs from 4, 4, 8 brain lobes, respectively).",
    "ncbi_link": "EGFP: 
Fasn1: 33524
GAL4: 855828
Hh: 42737
repo: 47285"
  },
  {
    "caption": "knockdown of Fasn1 in glial cells (repo-GAL4>), where Hh.N.EGFP is overexpressed, significantly reduces the number of Hh.N.EGFP puncta on the surface of NBs phenocopying the effect of Rasp knockdown, quantified in (G)",
    "ncbi_link": "EGFP: 
Fasn1: 33524
GAL4: 855828
Hh: 42737
Rasp: 44098
repo: 47285"
  },
  {
    "caption": "H) Cortex glial (NP2222-GAL4>) overexpression of Hh.N.EGFP significantly reduces NB EdU incorporation (n= 13,12 brain lobes).",
    "ncbi_link": "EGFP: 
NP2222: 
GAL4: 855828
Hh: 42737"
  },
  {
    "caption": "I) Knockdown of Fasn1 in glial cells rescues NB EdU incorporation defects, caused by glial Hh.N.EGFP overexpression, quantified in (I) (n=15, 13 brain lobes).",
    "ncbi_link": "EGFP: 
Fasn1: 33524
Hh: 42737"
  },
  {
    "caption": "(A) Representative EPSP and mEPSP electrophysiological traces from larval NMJs at Muscle 6 in which a motoneuron specific driver was used to overexpress either a control transgene (DVGlut-GAL4 > UAS-RFP), dNmnat (DVGlut-Gal4 > UAS-dNmnat), or Wnd (DVGlut-Gal4 > UAS-Wnd).",
    "ncbi_link": "RFP: 
GAL4: 855828
Gal4: 855828
dNmnat: 42987
DVGlut: 33427
Wnd: 40143"
  },
  {
    "caption": "(B) Quantification of mean (±SEM) EPSP amplitudes, in which 75 consecutive evoked events were averaged per cell, and then cell amplitudes were averaged per genotype. [UAS-RFP n = 13 cells, UAS-dNmnat n = 14 cells, UAS-Wnd n= 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=36, F=12.66, p<0.0001. UAS-RFP vs UAS-dNmnat p < 0.0001 (****), UAS-RFP vs UAS-Wnd p = 0.0093 (**)].",
    "ncbi_link": "RFP: 
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "]. (C) Quantification of mean (±SEM) mEPSP amplitudes, in which 75 consecutive spontaneous events were averaged per cell, and then cell amplitudes were averaged per genotype. [UAS-RFP n = 15 cells, UAS-dNmnat n = 14 cells, UAS-Wnd n= 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=38, F=11.66, p = 0.0001. UAS-RFP vs UAS-dNmnat p=0.994 (NS), UAS-RFP vs UAS-Wnd p = 0.0003 (***)].",
    "ncbi_link": "RFP: 
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(D) Quantification of quantal content, which was calculated individually per cell by dividing the mean EPSP amplitude by the mean mEPSP amplitude, and then averaged per genotype. [UAS-RFP n = 15 cells, UAS-dNmnat n = 14 cells, UAS-Wnd n= 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=38, F=9.286, p = 0.0006. UAS-RFP vs UAS-dNmnat p=0.0015 (**), UAS-RFP vs UAS-Wnd p = 0.0003 (***)].",
    "ncbi_link": "RFP: 
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(F) Quantification of the mean (±SEM) number of DVGlut+ boutons per muscle 4 NMJ in each genotype. [UAS-RFP n = 23, UAS-dNmnat n = 21, UAS-Wnd n= 20 NMJs. 1-way ANOVA w/Tukey's multiple comparisons, DF=63, F=68.31, p < 0.0001. UAS-RFP vs UAS-dNmnat p=0.9818 (NS), UAS-RFP vs UAS-Wnd p < 0.0001(****)].",
    "ncbi_link": "RFP: 
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(A) Representative EPSP and mEPSP physiological traces from larval NMJs at Muscle 6. Recordings were taken from WT control larvae (Elav-Gal4>UAS-RFP), hiw mutants driving a control transgene (hiwND8;Elav-Gal4 > UAS-RFP), and hiw mutants expressing RNAis to knockdown either dNmnat (hiwND8;Elav-Gal4 > UAS-dNmnat-RNAi [#29402] ) or Wnd (hiwND8;Elav-Gal4 > UAS-Wnd-RNAi [#25396]).",
    "ncbi_link": "RFP: 
Elav: 31000
Gal4: 855828
hiw: 32429
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(B) Quantification of mean (±SEM) EPSP amplitudes, in which 75 consecutive evoked events were averaged per cell, and then cell amplitudes were averaged per genotype. [WT n = 10 cells, hiw n = 10 cells, hiw > Wnd-RNAi n= 10 cells, hiw > dNmnat-RNAi n = 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=39, F=14.02, p<0.0001. WT vs hiw p = 0.0012 (**), WT vs hiw > Wnd-RNAi p < 0.0001 (****), WT vs hiw > dNmnat-RNAi p = 0.9880 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(C) Quantification of quantal content (±SEM). [WT n = 9 cells, hiw n = 9 cells, hiw > Wnd-RNAi n= 10 cells, hiw > dNmnat-RNAi n = 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=38, F= 2.508, p<0.0001. WT vs hiw p = 0.0361 (*), WT vs hiw > Wnd-RNAi p = 0.0001 (***), WT vs hiw > dNmnat-RNAi p = 0.9889 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(E) Quantification of the mean (±SEM) number of DVGlut+ boutons per muscle 4 NMJ in each genotype. [WT n = 23, hiw n = 21 , hiw > Wnd-RNAi n= 16, hiw > dNmnat-RNAi n=19. 1-way ANOVA w/Tukey's multiple comparisons, DF=78, F=169.1, p < 0.0001. WT vs hiw p < 0.0001 (****), WT vs hiw > Wnd-RNAi p = 0.9988 (NS), WT vs hiw > dNmnat-RNAi p < 0.0001 (****), hiw vs hiw > dNmnat-RNAi p = 0.9695 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987
Wnd: 40143"
  },
  {
    "caption": "(A) Representative images of immunostained larval NMJs and active zones from WT, hiw mutant, and hiw mutant driving an RNAi against dNmnat [#29402]. In the top 3 panels, greyscale images of entire terminal were acquired by staining for nerve marker HRP. Presynaptic Brp puncta (green) and postsynaptic dGluRIII clusters (magenta) were imaged to quantify N in each genotype.",
    "ncbi_link": "hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(B) Quantification of NMJ synaptic terminal surface area in each genotype. [WT n = 14, hiw n = 12 , hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=22.427, p < 0.0001. WT vs hiw p < 0.0001 (****), WT vs hiw > dNmnat-RNAi p < 0.0001 (****), hiw vs hiw > dNmnat-RNAi p = 0.2907 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(C) Quantification of BRP puncta per NMJ [WT n = 14, hiw n = 12, hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=2.854, p = 0.0711. WT vs hiw p = 0.0573 (NS), WT vs hiw > dNmnat-RNAi p = 0.4529 (NS), hiw vs hiw > dNmnat-RNAi p = 0.5030 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(D) Quantification of percentage of Brp puncta that were apposed to a dGluRIII clusters at each NMJ [WT n = 14, hiw n = 12, hiw > dNmnat-RNAi n=12. 1-way ANOVA w/Tukey's multiple comparisons, DF=37, F=2.093, p = 0.4716. WT vs hiw p = 0.2168 (NS), WT vs hiw > dNmnat-RNAi p = 0.1882 (NS), hiw vs hiw > dNmnat-RNAi p = 0.9966 (NS)].",
    "ncbi_link": "hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(E) Representative electrophysiological traces from a synaptic facilitation experiment in which trains of 5 pulses were used to evoke consecutive action potentials at 100 ms ISI. Genotypes for these experiments were: WT (elav>UAS-RFP), hiw mutant (hiw; elav>UAS-RFP), or hiw depleted of dNmnat (hiw; elav>dNmnat-RNAi). (F) Quantification of the facilitation index, in which the amplitude of the 5th pulse is divided by the amplitude of the 1st pulse. [100 ms ISI: WT n=11, hiw n= 9, hiw>dNmnat-RNAi n= 12. 1-way ANOVA w/Tukey's multiple comparisons, DF = 31, F= 7.546, p =0.0023. WT vs hiw p =0.0020 (**), hiw vs hiw> dNmnat-RNAi p= 0.0229 (*), WT vs hiw> dNmnat-RNAi p= 0.5141 (NS). 50 ms ISI: WT n=11, hiw n= 9, hiw>dNmnat-RNAi n= 12. 1-way ANOVA w/Tukey's multiple comparisons, DF = 31, F= 5.587, p =0.0089. WT vs hiw p =0.0129 (*), hiw vs hiw> dNmnat-RNAi p= 0.0217 (*), WT vs hiw> dNmnat-RNAi p= 0.9546 (NS).]",
    "ncbi_link": "RFP: 
elav: 31000
hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(A) Representative images of NMJ synaptic terminals in control (DVGlut-Gal4 > UAS-HA-dNmnat) and hiw mutant (hiwND9,DVGlut-Gal4 > UAS-HA-dNmnat) larvae. NMJs at larval muscle 4 were identified using HRP (blue in top panel) immunostaining. Insets highlight active zones within single boutons, which were identified by staining for the presynaptic active zone protein Brp (red). An anti-HA antibody was used to stain for an HA-tagged dNmnat (green) transgene to measure protein levels in control and hiw mutant active zones.",
    "ncbi_link": "HA: 
Gal4: 855828
hiw: 32429
dNmnat: 42987
DVGlut: 33427"
  },
  {
    "caption": "(B) Quantification of HA-dNmnat levels across the entire NMJ synaptic terminal, normalized to total terminal area and presented as fold change over WT. [WT > HA-dNmnat n = 10 terminals, hiw > HA-dNmnat n = 10 terminals. Unpaired T-test, DF = 18, p = 0.0028 (**)].",
    "ncbi_link": "HA: 
hiw: 32429
dNmnat: 42987"
  },
  {
    "caption": "(C) Quantification of HA-dNmnat levels per unit area in WT and hiw for synaptic terminals excluding active zones (herein referred to as \"terminals\") versus active zones (AZs) only. [WT n = 10 terminals, hiw n = 9 terminals, each parsed into terminal minus AZs and AZs only. 2-way ANOVA with Tukey's multiple comparisons, DF = 34, p = 0.0005 for row factor (terminal versus AZs) and p < 0.0001 for column factor (WT vs hiw). WT terminal vs hiw terminal p = 0.9830 (NS). Hiw terminal vs hiw AZs p < 0.0001 (****). WT AZs vs hiw AZs p < 0.0001 (****).]",
    "ncbi_link": "hiw: 32429
Hiw: 32429"
  },
  {
    "caption": "A) Representative electron micrographs of entire boutons in wild type, hiw;wnd, and hiw;wnd, Elav-GAL4 > dNmnat RNAi NMJs.",
    "ncbi_link": "Elav: 31000
GAL4: 855828
hiw: 32429
dNmnat: 42987
wnd: 40143"
  },
  {
    "caption": "B) High magnification electron micrographs showing representative "T-bar" structures at active zones in NMJs of the indicated genotypes. Red arrows denote the beginning and end of the T-bar top, demonstrating changes in T-bar width in the genotypes tested. As illustrated, a significant reduction in T-bar size is observed in hiw;wnd, and this defect is suppressed in hiw;wnd, Elav-GAL4 > dNmnat RNAi.",
    "ncbi_link": "Elav: 31000
GAL4: 855828
hiw: 32429
dNmnat: 42987
wnd: 40143"
  },
  {
    "caption": "C) Quantification of mean T-bar width [WT n = 90, hiw;wnd n = 55, hiw;wnd, Elav-GAL4 > dNmnat RNAi n=81. 1-way ANOVA w/Tukey's multiple comparisons, DF=225, F=13.829, p < 0.0001. WT vs hiw;wnd p < 0.0001 (****), WT vs hiw;wnd, Elav-GAL4 > dNmnat RNAi p = 0.9318 (NS), hiw;wnd vs hiw;wnd, Elav-GAL4 > dNmnat RNAi p < 0.0001 (****)]. (D) Analysis of cumulative frequency distribution of T-bar width shows a left shift in distribution in hiw;wnd but no change in hiw;wnd, Elav-GAL4 > dNmnat RNAi compared with WT NMJs [WT vs hiw;wnd K-S test, D=0.5636, p < 0.0001 (****), WT vs hiw;wnd, Elav-GAL4 > dNmnat RNAi K-S test, D=0.1815, p = 0.1240 (NS), hiw;wnd vs hiw;wnd, Elav-GAL4 > dNmnat RNAi K-S test, D=0.4121, p < 0.0001 (****)].",
    "ncbi_link": "Elav: 31000
GAL4: 855828
hiw: 32429
dNmnat: 42987
wnd: 40143"
  },
  {
    "caption": "]. (E) Quantification of mean T-bar height [WT n = 90, hiw;wnd n = 55, hiw;wnd, Elav-GAL4 > dNmnat RNAi n=81. 1-way ANOVA w/Tukey's multiple comparisons, DF=225, F=10.472, p < 0.0001. WT vs hiw;wnd p = 0.0008 (***), WT vs hiw;wnd, Elav-GAL4 > dNmnat RNAi p = 0.6694 (NS), hiw;wnd vs hiw;wnd, Elav-GAL4 > dNmnat RNAi p < 0.0001 (****)] (F) Analysis of cumulative frequency distribution of T-bar height shows a left shift in distribution in hiw;wnd but no change in hiw;wnd, Elav-GAL4 > dNmnat RNAi compared with WT NMJs [WT vs hiw;wnd K-S test, D=0.3343, p = 0.001 (***), WT vs hiw;wnd, Elav-GAL4 > dNmnat RNAi K-S test, D=0.1012, p = 0.7748 (NS), hiw;wnd vs hiw;wnd, Elav-GAL4 > dNmnat RNAi K-S test, D=0.3484, p = 0.0008 (***)].",
    "ncbi_link": "Elav: 31000
GAL4: 855828
hiw: 32429
dNmnat: 42987
wnd: 40143"
  },
  {
    "caption": "(B) Representative EPSP and mEPSP electrophysiological traces from larval NMJs at Muscle 6 in which a motoneuron specific driver was used to overexpress either a control transgene (DVGlut-GAL4 > UAS-RFP), or one of the catalytic dNmnat mutants (DVGlut-Gal4 > UAS-WR-dNmnat, DVGlut-Gal4 > UAS-H30A-dNmnat).",
    "ncbi_link": "RFP: 
GAL4: 855828
Gal4: 855828
dNmnat: 42987
DVGlut: 33427"
  },
  {
    "caption": "(C) Quantification of mean (±SEM) EPSP amplitudes, in which 75 consecutive evoked events were averaged per cell, and then cell amplitudes were averaged per genotype. [UAS-RFP n = 8 cells, UAS-WR-dNmnat n = 7 cells, UAS-H30A-dNmnat n= 7 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=21, F=0.8596, p = 0.4383. UAS-RFP vs UAS-WR-dNmnat p = 0.8810 (NS), UAS-RFP vs UAS-H30A-dNmnat p = 0.9997 (NS)].",
    "ncbi_link": "RFP: 
dNmnat: 42987"
  },
  {
    "caption": "(D) Quantification of quantal content (±SEM) [UAS-RFP n = 8 cells, UAS-WR-dNmnat n = 7 cells, UAS-H30A-dNmnat n= 7 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=21, F=1.154, p = 0.3365. UAS-RFP vs UAS-WR-dNmnat p = 0.8696 (NS), UAS-RFP vs UAS-H30A-dNmnat p = 0.9697 (NS)].",
    "ncbi_link": "RFP: 
dNmnat: 42987"
  },
  {
    "caption": "]. (E) Representative EPSP and mEPSP electrophysiological traces from larval NMJs at Muscle 6. Recordings were taken from WT control larvae (Elav-Gal4>UAS-RFP), hiw mutants driving a control transgene (hiwND8;Elav-Gal4 > UAS-RFP), and hiw mutants expressing an RNAi to knockdown NAD+syn (hiwND8;Elav-Gal4 > UAS-NAD+syn-RNAi).",
    "ncbi_link": "RFP: 
Elav: 31000
Gal4: 855828
hiw: 32429
NAD+syn: 32328"
  },
  {
    "caption": "(F) Quantification of mean (±SEM) EPSP amplitudes, in which 75 consecutive evoked events were averaged per cell, and then cell amplitudes were averaged per genotype. [WT n = 10 cells, hiw n = 10 cells, hiw > NADsyn-RNAi n = 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=29, F=14.02, p<0.0001. WT vs hiw p <0.0001 (****), WT vs hiw > NADsyn-RNAi p = 0.5147 (NS)].",
    "ncbi_link": "hiw: 32429
NADsyn: 32328"
  },
  {
    "caption": "]. (G) Quantification of quantal content. [WT n = 10 cells, hiw n = 10 cells, hiw > NADsyn-RNAi n = 10 cells. 1-way ANOVA w/Tukey's multiple comparisons, DF=29, F= 6.635, p = 0.0047. WT vs hiw p = 0.0063 (**), WT vs hiw > NADsyn-RNAi p = 0.8942 (NS)].",
    "ncbi_link": "hiw: 32429
NADsyn: 32328"
  },
  {
    "caption": "(I) Quantification of the mean (±SEM) number of DVGlut+ boutons per muscle 4 NMJ in each genotype. [WT n = 25, hiw n = 21, hiw > NADsyn-RNAi n=24. 1-way ANOVA w/Tukey's multiple comparisons, DF=67, F=141.3, p < 0.0001. WT vs hiw p < 0.0001 (****), WT vs hiw > Nadysn-RNAi p > 0.0001 (****)].",
    "ncbi_link": "hiw: 32429
NADsyn: 32328
Nadysn: 32328"
  },
  {
    "caption": "c, Percentage of bacteria coated by the indicated galectin 8 alleles. HeLa cells stably expressing the indicated galectin 8 alleles fused to YFP were infected with S. Typhimurium. YFP-positive S. Typhimurium were counted by microscopy at 75 min p.i. WT, wild type.",
    "ncbi_link": "galectin 8: 3964"
  },
  {
    "caption": "d, Binding of galectin 8 to bacteria and HeLa cells. The indicated bacteria and HeLa cells were incubated with His-GST-ubiquitin (Ub), His-GST-galectin 8 or buffer as indicated, followed by murine anti-His antibody and PE-labelled anti-mouse serum.",
    "ncbi_link": "galectin 8: 3964"
  },
  {
    "caption": "g, Fold replication of S. Typhimurium in HeLa cells expressing the indicated galectin 3 variants and transfected with the indicated siRNAs. At 2 h and 6 h after infection, cells were lysed and bacteria counted on the basis of their ability to form colonies on agar plates. Galectin 3 proteins are further characterized in Supplementary Fig. 4b. Mean and s.d. of duplicate coverslips>100 bacteria counted per coverslip. Data are representative of at least two repeats. *P< 0.05, Student's t-test. Scale bar, 10 µm.",
    "ncbi_link": "galectin 3: 3958"
  },
  {
    "caption": "a, Confocal micrograph of HeLa cells expressing GFP-LC3 and mCherry-galectin-8, stained for NDP52 1 h after infection with S. Typhimurium. The lower right panel contains a fluorescence line scan along the yellow line in the merge inset. Arrowheads, bacteria shown in insets.",
    "ncbi_link": "galectin-8: 3964
LC3: 440738///81631///84557"
  },
  {
    "caption": "c, Percentage of bacteria positive for NDP52. HeLa cells expressing the indicated NDP52 variants fused to YFP were infected with S. Typhimurium.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "d, Percentage of bacteria positive for the indicated markers. HeLa cells, either wild type or expressing YFP-galectin-8 as indicated, were infected with S. Typhimurium. Ubiquitin was detected by antibody staining.",
    "ncbi_link": "galectin-8: 3964"
  },
  {
    "caption": "B Latency to enter dark compartment for Gadd45a-WT (white bars, n=11) and Gadd45a-KO (blue bars, n=11). A significant reduction was found in the Gadd45a-KO at 24 hours and 7 days after the training. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni post-hoc test: * = p<0.05.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "C In situ hybridization to detect Gadd45a mRNA in adult wild-type hippocampus (n=8 animals; antisense, left panel; sense, middle panel) and in Gadd45a-KO sections (n=6 animals; right panel). Scale bars: 500 µm (black bar).",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "D Experience-dependent changes in mRNA levels were evaluated under control conditions (home cage) and exposed to the PA (context, and context + shock groups; n=6 for all groups), respectively. Hippocampal Gadd45a mRNA levels remained unchanged, while Gadd45b was induced (context; t10=2.427, context + shock t10=2.319). Concomitantly, mRNA levels of activity-regulated cytoskeleton protein (Arc), as a proxy of neuronal activation, were increased in mice exposed to the PA context (t10=3.406) and context + shock (t10=3.141). Values shown are mean ± SEM; 1-Way ANOVA and unpaired t-test: * = p<0.05, *** = p<0.001.",
    "ncbi_link": "Arc: 11838
Gadd45a: 13197
Gadd45b: 17873"
  },
  {
    "caption": "Gadd45a mRNA level in the hippocampus of Gadd45a-overexpressing mice (red, n=7) was significantly increased (t10=4.189) as compared to Gadd45a-WT (n=5). Values shown are mean ± SEM; unpaired t-test: ** = p<0.01.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "C Immunohistochemistry for hemagglutinin (HA, fused to Gadd45α) in Gadd45a-WT (Nex-Cre(-/-), n=5) and Gadd45a-overexpressing hippocampi (Nex-Cre(+/-), n=5) 8 weeks after AAV injection. Note that the Gadd45α-HA signal in Gadd45a-overexpressing mice is predominantly found in the stratum pyramidale (sp) but also in the stratum oriens and stratum radiatum (so and sr, respectively). Scale bar: 250 µm.",
    "ncbi_link": "Cre: 2777477
Gadd45a: 13197
Nex: 11922"
  },
  {
    "caption": "D Cellular distribution of Gadd45α was analyzed by HA-western blot on nuclear and cytoplasmic protein fractions of Gadd45a-WT and Gadd45a-overexpressing mice (n=2 for both groups). HA was found predominantly in the nuclear fraction of Gadd45a-overexpressing hippocampi, with a smaller but recognizable expression also in the cytoplasm.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "E Latency to enter the dark compartment for Gadd45a-WT (white bars, n=10) and Gadd45a-overexpressing mice (red bars, n=12) in the PA test. A significant increase was found 24 hours and 7 days after the PA training in the Gadd45a-overexpresion group. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni Post-hoc test: * = p<0.05.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "B LTP protocol was applied to 16 slices of Gadd45a-WT mice (white dots, n=5 animals) and 11 slices of Gadd45a-KO mice (blue dots, n=5 animals), resulting in a significantly (p<0.05, Student t-test) lowered induction of LTP in Gadd45a-KO mice as compared with Gadd45a-WT. Values shown are mean ± SEM. C Gadd45a-overexpressing mice (red dots, n=10 slices from 6 animals) presented a slightly increased LTP as compared with Gadd45a-WT (white dots, n=8 slices from 6 animals), which became more pronounced during the late phase of the experiment. Values shown are mean ± SEM. ",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "D UCSC browser view of reads-per-million-normalised RNA-seq coverage for Grin2a in Gadd45a-WT (black) and Gadd45a-KO (blue) representative samples. Gene structure of Grin2a (colored in purple), and the direction of transcription (red arrow). Upper pannel covers the entire transcript while lower panel is an enlargement of exons 4-8.",
    "ncbi_link": "Gadd45a: 13197
Grin2a: 14811"
  },
  {
    "caption": "E Detailed view of the extended 3´UTR of Grin2a showing a significant 5´<3´ gradient in RNA-seq coverage. Note that the normalised read coverage is similar between genotypes at the actual 3´UTR end but differs significantly upstream including the annotated exons. For subsequent experiments, position of the designed primers covering proximal and distal parts of the 3´UTR are indicated below.",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": "F, G Validation of Gadd45α-regulated levels of Grin2a mRNA by qPCR with primers covering exons 3-4. Grin2a mRNA levels were analyzed in the hippocampus of mice under control conditions (white bars; Gadd45a-WT=7 and Gadd45a-KO=7) and 1 hour after PA (Gadd45a-WT=5, black bars; Gadd45a-KO=6, blue bars). Random primed cDNA levels (F), were very similar in all the experimental groups. Oligo(dT)-primed cDNA (G) revealed a significant increase of Grin2a 1h after PA, which was only observed in Gadd45a-WT mice. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni post-hoc test: ** = p<0.01, *** = p<0.001. H, I mRNA levels of proximal vs. distal parts of the 3´UTR analyzed in the same set of oligo(dT)-primed cDNA. (H) Significant increase in Grin2a mRNA levels was found for the proximal part only in Gadd45a-WT. (I) Distal parts of the 3´UTR remained unchanged (n=6 for all groups). Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni post-hoc test: * = p<0.05. ",
    "ncbi_link": "Gadd45a: 13197
Gadd45α: 13197
Grin2a: 14811"
  },
  {
    "caption": "A, B NR2A protein levels were analyzed in the hippocampus of mice under control conditions (white bars; Gadd45a-WT, n=13 and Gadd45a-KO, n=14) and 1 hour after PA (black bars; Gadd45a-WT=14, Gadd45a-KO=14). NR2A signal (160 kDa) was normalized to the loading control (tubulin (55 kDa) for the total fraction, and synaptotagmin (68 kDa) for the synaptosomal fraction) and calculated as percentage of control. In Gadd45a-WT samples (A), NR2A protein levels were unchanged in the total fraction during memory formation, while in the synaptosomal fraction, a significant increase was detected (t20=3.199). In Gadd45a-KO hippocampi (B), levels of NR2A protein in both fractions remained unaltered during memory consolidation. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni post-hoc test: ** = p<0.01.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "C Gadd45α pulldown experiments were carried out in wild-type hippocampal lysates (n=12 for all groups). Percentage of input recovery was unchanged between GFP-FLAG (green bars) and Gadd45α-FLAG (black bars) for genes that are not regulated by Gadd45α, such as succinate dehydrogenase complex flavoprotein subunit A (Sdha, no 3´UTR extension), and mitogen-activated protein kinase 6 (Map2K6, containing 3´UTR extension of 10 kb). On the contrary, Gadd45α-FLAG bound fraction revealed a significant increase in Grin2a (t22=4.992) and Grm5 mRNA (t22=4.939) as compared to GFP-FLAG fraction. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni Post-hoc test: *** = p<0.001.",
    "ncbi_link": "Grin2a: 14811
Grm5: 108071
Map2K6: 26399
mitogen-activated protein kinase 6: 26399
Sdha: 66945
succinate dehydrogenase complex flavoprotein subunit A: 66945"
  },
  {
    "caption": "B Hippocampal Gadd45a mRNA levels were significantly upregulated in both Gadd45a-overexpression (q24 = 4.094) and Gadd45aK45E-overexpression groups (q24 = 4.726) (n=9 for all groups). Values shown are mean ± SEM; Tukey´s multiple comparison test: * = p<0.05, ** = p<0.01.",
    "ncbi_link": "Gadd45a: 13197"
  },
  {
    "caption": "C Immunohistochemistry for hemagglutinin (HA, fused to Gadd45α) in Gadd45a-WT (left), Gadd45a-overexpression (middle) and Gadd45aK45E-overexpression (right) samples 8 weeks after AAV injection (n=3 for all groups). Upper row depicts the entire hippocampus, while center and lower rows show magnifications of the CA3 area in which the HA signal (red) is not restricted to the nuclei (blue and white). Scale bar: 250 µm.",
    "ncbi_link": "Gadd45a: 13197
Gadd45α: 13197"
  },
  {
    "caption": "D Gadd45α-overexpression was confirmed at the protein level by HA-western blot on hippocampal samples from Gadd45a-WT, Gadd45a-overexpression and Gadd45aK45E-overexpression mice (n=3 for all groups). Hippocampus scale bars: 250 µm; CA3 scale bars: 50µm.",
    "ncbi_link": "Gadd45a: 13197
Gadd45α: 13197"
  },
  {
    "caption": "E Latency to enter the dark compartment for Gadd45a-WT (white bars, n=12), Gadd45a-overexpression (red bars, n=11) and Gadd45aK45E-overexpression mice (grey bars, n=11) in the PA test. Note that, unlike Gadd45a-overexpression mice, those expressing the mutated form of Gadd45α (no RNA-binding capacity) did not show an increase in memory retention. Values shown are mean ± SEM; 2-Way ANOVA and Bonferroni Post-hoc test: * = p<0.05, *** = p<0.001.",
    "ncbi_link": "Gadd45a: 13197
Gadd45α: 13197"
  },
  {
    "caption": " (B, C) Representative immunoblots (B) and quantification of Tau degradation (C) from 14 DIV primary neurons transduced with EGFP or shTSG101, treated for 24 h with either DMSO (CON) or cycloheximide (CHX), and probed for Tau and tubulin. shTSG101-expressing neurons exhibit markedly decreased Tau degradation compared to EGFP-expressing controls (n=18-19 per condition, unpaired student's t-test, *p=0.0108) ",
    "ncbi_link": "TSG101: 292925"
  },
  {
    "caption": " (D, E) Representative immunoblots (D) and quantification of Tau degradation (E) from 14 DIV neurons transduced with mCh or mCh-TSG101, treated for 24 h with either DMSO (CON) or cycloheximide (CHX), and probed for Tau and tubulin. Overexpression of TSG101 increases Tau degradation (n=17/condition, unpaired student's t-test, *p=0.0115) ",
    "ncbi_link": "TSG101: 292925"
  },
  {
    "caption": " (F, G) Representative immunoblots (F) and quantification of Tau degradation (G) from 14 DIV neurons transduced with mCh or shRab35, treated for 24 h with either DMSO (CON) or cycloheximide (CHX), and probed for Tau and tubulin. shRab35-expressing neurons exhibit markedly decreased Tau degradation compared to mCh-expressing controls (n=23-26 per condition, unpaired student's t-test, ***p=0.0008)",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (H, I) Representative immunoblots (H) and quantification of Tau degradation (I) from 14 DIV neurons transduced with mCh or mCh-Rab35, treated for 24 h with either DMSO (CON) or cycloheximide (CHX), and probed for Tau or tubulin. Rab35 overexpression increases Tau degradation (n=18 per condition, unpaired student's t-test, *p=0.0126)",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (J) Flow cytometry distribution of N2a cells cotransfected with either HA vector (black) or HA-Rab35 (green) and medium fluoresence timer-tagged wild-type Tau (FT-Tau); blue fluorescence (y axis) indicates \"younger\" Tau protein while red fluorescence (x axis) indicates \"older\" Tau",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": " (K) The ratio of cells expressing red to blue (older:younger) FT-Tau is reduced in cells overexpressing Rab35, indicating faster Tau turnover (n=9/condition, unpaired student's t-test , ****p<0.0001) ",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": " (A, B) Representative immunoblots (A) and quantification of Tau degradation (B) from 14 DIV primary neurons transduced with mCh or shRab35, treated for 24 h with either DMSO (CON) or cycloheximide (CHX), and probed for pSer396/404-Tau (PHF1), pSer262-Tau, or pSer202-Tau (CP13) and tubulin. shRab35-expressing neurons exhibit markedly decreased pSer262- and p396/404-Tau degradation compared to mCh-expressing controls, while pSer202-Tau degradation is unaffected (n=4 per condition for pSer396/404-Tau and pSer202-Tau, n=3 for pSer262-Tau, unpaired student's t-test, **p=0.0027, *p=0.0120) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (C) Images of PLA signal (green) for Hrs/Tau interaction in N2a cells co-transfected with FLAG-Hrs and either mCh or mCh-Rab35 (red), and probed with antibodies against FLAG and total (DA9) or phospho-Tau species (pSer396/404-Tau, pSer262-Tau, or pSer202-Tau); scale bar: 5 μm. (D) Rab35 overexpression significantly increases PLA puncta for total, pSer396/404-Tau, pSer262-Tau but not pSer202-Tau (n=121-132 cells for total Tau, 178-195 cells for pSer396/404-Tau, 71-98 cells for pSer262-Tau, 25-29 cells for pSer202-Tau; Mann-Whitney test, ****p<0.0001) ",
    "ncbi_link": "Rab35: 77407
Hrs: 56324"
  },
  {
    "caption": " (C) Rab35 mRNA levels are decreased by GC in 14 DIV hippocampal neurons and N2a cells (for neurons, n=9/condition, unpaired student's t-test, **p=0.0036; for N2a cells, n=6/condition, unpaired student's t-test, *p=0.0138) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (A, B) Representative immunoblots (A) and quantification of Tau degradation (B) in 14 DIV neurons expressing mCh-Rab35 or mCh, treated for 24 h with cycloheximide (CHX) or DMSO (CON) under GC conditions. GC significantly decreases Tau degradation, whereas Rab35 overexpression blocks this effect (n=12-14/condition; 1-way ANOVA, Dunnet post-hoc analysis, *pmCh vs mCh GC=0,0319, *pmCh vs Rab35 GC=0,047) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (D, E) Representative immunoblots (D of Tau levels (E) in hippocampal synaptosomes reveal that GC increases total Tau levels in animals expressing EGFP, but not Rab35 (n=5-6 animals/group, 2 replicates, 2-way ANOVA, GC x Rab35 interaction F1, 39=10,51 p=0.002; Sidak posthoc analysis *p=0.0168)",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (G) GC treatment reduces the length of apical dendrites in animals expressing EGFP, but not EGFP-Rab35 (n=6-7 animals/group; 6-8 neurons/animal, 2-way ANOVA , GC x Rab35 interaction F1, 155=3.969 p=0.0481, overall GC effect F1, 155=8.998 p=0.0031, Sidak posthoc analysis **p=0.0021) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (H) GC treatment reduces mature spine density in animals expressing EGFP, but not EGFP-Rab35 (2-way ANOVA, GC x Rab35 interaction F1, 499=12.33 p=0.0005, overall GC effect F1, 499=4.373 p=0.0370, Sidak posthoc analysis *** p=0.0003; n=6-7 animals/group; 6-8 neurons per animal) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": " (I, J) Sholl analysis of apical dendrites in rat hippocampus shows reduced dendritic intersections after GC treatment in EGFP-expressing animals; however, this effect is not seen in EGFP-Rab35-expressing animals (3-way ANOVA, GC x Rab35 interaction F1, 4212= 14,926 p<0.0001, Simple effect analysis, Sidak test for multiple comparisons *p120=0.012, **p140=0.001, **p220=0.002, ***p240<0.001, ***p260<0.001, **p280=0.001, **p300=0.001, *p320=0.021, *p340=0.047, n=6-7 animals/group, 6-8 neurons per animal) ",
    "ncbi_link": "Rab35: 288700"
  },
  {
    "caption": "B Western blots  of eEF2  in the PFC, the rest part of cortex, the hippocampus, and the striatum  of Eef2  WT and HET mice.",
    "ncbi_link": "Eef2: 13629"
  },
  {
    "caption": "D Representative merged immunofluorescent staining  images of eEF2  (green) and CaMKⅡα  (red) in the mPFC  of Eef2  WT and HET mice. Scale bar, 10 μm. E Quantification of mean fluorescent intensity of eEF2  in CaMKⅡα+ cells in WT and HET mPFC. n=918 cells from 3 WT mice, n=965 cells from 3 HET mice. Unpaired t test. **** p<0.0001. Data information: All data are shown as means ± s.e.m. All the tests are two-tailed.",
    "ncbi_link": "Eef2: 13629"
  },
  {
    "caption": "F Representative merged immunofluorescent staining  images of eEF2  (green) and GAD65/67 (red) in the mPFC  of Eef2  WT and HET mice. Scale bar, 10 μm. G Quantification of mean fluorescent intensity of eEF2  in GAD65/67+ cells in WT and HET mPFC. n=690 cells from 3 WT mice, n=686 cells from 3 HET mice. Mann-Whitney test. p=0.6757. Data information: All data are shown as means ± s.e.m. All the tests are two-tailed.",
    "ncbi_link": "Eef2: 13629"
  },
  {
    "caption": "L Representative immunofluorescent  images of eEF2  (magenta) and PLA  signals (white) in lentivirus  (LV)-scramble-EGFP  or LV-Eef2  shRNA-EGFP  infected primary cortical neurons (green, DIV 14). Scale bar, 10 μm. M Quantification of mean fluorescent intensity of eEF2  in EGFP+ cells in scramble and Eef2  shRNA groups. 64 cells for scramble group and 51 cells for Eef2  shRNA group from 3 independent experiments. Mann-Whitney test. ****p<0.0001. N Quantification of mean fluorescent intensity of PLA  signals in EGFP+ cells in the two groups. The PLA  signals represent newly synthesized GluA2. 64 cells for scramble group, 51 cells for Eef2  shRNA group from 3 independent experiments. Mann-Whitney test. ****p<0.0001. Data information: All data are shown as means ± s.e.m. All the tests are two-tailed.",
    "ncbi_link": "EGFP: 
Eef2: 29565"
  },
  {
    "caption": "E Representative heatmaps of the two social tasks (left, social approach; right, social novelty) in the Three-chamber test performed by Eef2 HET mice intraperitoneal administered with PF-4778574 or DMSO (vehicle control). E: empty cup; S1: stranger #1 contained cup; S2: stranger #2 contained cup. F Discrimination score of social approach performed by two groups of mice, calculated by the difference of time spent in sniffing S1 and E. Unpaired t test. p=0.7335. WT, n=9 mice; HET, n=8 mice. G Discrimination score of social novelty performed by two groups of mice, calculated by the difference of time spent in sniffing S2 and S1. Unpaired t test. *p=0.0492. WT, n=9 mice; HET, n=8 mice. Data information: Data F, G, are shown as interquartile range, with line across the box indicating median, whiskers show the highest and lowest values. n.s., not significant. All the t tests are two-tailed.",
    "ncbi_link": "Eef2: 13629"
  },
  {
    "caption": "I Representative heatmaps of the two social tasks (left, social approach; right, social novelty) performed by Eef2 HET mice with mPFC infusion of PF-4778574 or DMSO (vehicle control) in the Three-chamber test. E: empty cup; S1: stranger #1 contained cup; S2: stranger #2 contained cup. J Discrimination score of social approach performed by two groups of mice, calculated by the difference of time spent in sniffing S1 and E. Unpaired t test. p=0.3984. n=11 mice for each group. K Discrimination score of social novelty performed by two groups of mice, calculated by the difference of time spent in sniffing S2 and S1. Unpaired t test. *p=0.0489. n=11 mice for each group. Data information: Data of J and K are shown as interquartile range, with line across the box indicating median, whiskers show the highest and lowest values. n.s., not significant. All the t tests are two-tailed.",
    "ncbi_link": "Eef2: 13629"
  },
  {
    "caption": "A) Ptc protein distribution in a wing disc (3D reconstitution) under down-regulation of the SNARE proteins Syb and Syt1 in the dorsal compartment (D), keeping the ventral compartment (V) as a WT internal control. Note the basal accumulation of endogenous Ptc (arrowheads) when knocking down Syb or Syt1.",
    "ncbi_link": "Syb: 36080
Syt1: 33473"
  },
  {
    "caption": "B) Confocal images of immuno-labelled endogenous Ptc and cytonemes stabilized with Ihog-RFP protruding from Hh producing cells in wild type receiving cells (left panel), or B') when either blocking exocytosis by down-regulating Syb (middle panel) or B'') blocking endocytosis by expressing a dominant negative form of the Drosophila Dynamin, Shibire (right panel) in the Hh-receiving cells. Endogenous Ptc in wild type conditions cannot be visualized due to its rapid internalization and processing after Hh reception; while blocking exocytosis causes an accumulation of basal Ptc in intracellular punctae (arrowheads), and endocytosis inhibition leads to Ptc accumulation at the plasma membrane (arrows).",
    "ncbi_link": "Dynamin: 45928
Shibire: 45928
Syb: 36080"
  },
  {
    "caption": "C) Confocal apical (left) and basal (right) images of a shits mutant wing disc expressing Syb RNAi dorsally (D) to also block exocytosis, keeping the ventral compartment (V) as an internal control where just endocytosis is inhibited. After dorsal Syb RNAi induction, endocytosis was inhibited in the whole shits disc by incubation at restrictive temperature. Note the dorsal reduction of Ptc at plasma membrane after blocking exocytosis.",
    "ncbi_link": "shi: 45928
Syb: 36080"
  },
  {
    "caption": "D) Quantification of Ptc-GFP levels (Yac construct) along the wing disc apico-basal axis, integrating both fluorescence intensity and signal area (Integrated Density). The graph on the left shows values for wild type situations in purple (average in blue), while Syb RNAi treatment values are shown in green (average in orange). a clear shift of higher values towards the basal side of the discs after inhibition of Syb function. The graph to the right shows correlation coefficients between the maximum Ptc value and distance from the basal side (-1=basal, +1=apical) of discs after RNAi expression for different SNARE proteins and the wild type. Central horizontal lines show median values of N=7-16, box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. A basal association is particularly noticeable for Syb, Syx1A and α-Snap down-regulation. Right panel is a scheme illustrating the wild type and RNAi-treated patterns of quantified Ptc-GFP levels distribution along the wing disc apico-basal axis.",
    "ncbi_link": "Yac: 
α-Snap: 40233
Syb: 36080
Syx1A: 42854"
  },
  {
    "caption": "A) Electron Microscopy imaging of wing discs expressing the UAS-Ptc-GFP construct for 24 hours in receiving cells using Ptc-Gal4; TubGal80ts. Left panel shows areas with anti-GFP immuno-labelling (marked in blue) throughout the apico/basal axis of the wing disc epithelium a) anti-GFP gold-labelling corresponding to Ptc is located on the apical membrane and early endosomes towards MVB formation. b) Ptc immuno-gold labelling is present in multivesicular bodies (MVBs) subapically (top right panels). b1) subapical MVBs appear as less dense with greater Ptc labelling on the MVB outer membranes. c) Ptc label is also present in MVBs close to the basal membrane (lower right panels), c1) basolateral Ptc MVBs are significantly denser and richer in Ptc positive intraluminal vesicles (ILV).",
    "ncbi_link": "Gal4: 
Gal80: 
GFP: 
Ptc: 35851
Tub: 40554"
  },
  {
    "caption": "B) Endogenous Ptc subcellular localization after endocytosis inhibition by the dorsal expression of a dominant negative form of Rab5. The top panel is a schematic representation of the localized expression. The left panel is a digital 3D reconstruction and the right panel shows an apical and basal confocal sections. that accumulation of Ptc occurs at both the apical and basal sides of the dorsal part of the disc, compared to the wild type control on the ventral side.",
    "ncbi_link": "Rab5: 33418"
  },
  {
    "caption": "accumulation of Ptc occurs at both the apical and basal sides of the dorsal part of the disc, compared to the wild type control on the ventral side. C) Digital 3D reconstruction (left) and apical and basal confocal sections (right) of endogenous Ptc localization after endocytosis inhibition by the dorsal expression of a dominant negative form of shibire.",
    "ncbi_link": "shibire: 45928"
  },
  {
    "caption": "A) 3D reconstructions of immuno-labelled endogenous Ptc of wing discs in wild type condition and after RNAi expression for different ESCRT complex components. All RNAis' expression result in Ptc accumulation in large structures, located apically under Hrs (ESCRT-0 component) inhibition, and basally under inhibition of the ESCRT components I (Tsg101), II (Vps22) and III (Shrub). Graphs depicting signal values from apical to basal show a shift of higher intensity curves either towards acute apical or basal accumulation.",
    "ncbi_link": "Hrs: 33458
Shrub: 35933
Vps22: 11267
Tsg101: 39881"
  },
  {
    "caption": "B) Detailed confocal imaging of immuno-labelled endogenous Ptc localization after clonal Tsg101 down-regulation. The image shows abnormal accumulation of Ptc clusters in basal cytonemes emanating from receiving cells (arrows), since in wild type conditions Ptc visualization at basal membranes is not possible due to its rapid internalization and processing after Hh reception",
    "ncbi_link": "Tsg101: 39881"
  },
  {
    "caption": "C) Ptc accumulation in these punctated structures (arrows) is also visualized on receiving cytonemes stabilized with the co-receptor Ihog-RFP and after Tsg101 inhibition.",
    "ncbi_link": "Tsg101: 39881"
  },
  {
    "caption": "D) 3D reconstruction of Hh producing cytoneme network stabilized by Ihog-RFP shows that Ptc accumulation after Tsg101 treatment localizes above the signal sending cytoneme extensions (arrow).",
    "ncbi_link": "Tsg101: 39881"
  },
  {
    "caption": "A) Confocal image of wing disc expressing the human tetraspanin CD63-GFP expressed in the Hh receiving cells colocalizing with Ptc (Bac.Ptc-cherry) in vesicle-like structures (yellow arrows) along basal cytonemes.",
    "ncbi_link": "cherry: 
Ptc: 35851"
  },
  {
    "caption": "B) In vivo confocal frames of abdominal histoblasts showing colocalization of CD63-Cherry and Ptc (Yac.Ptc-GFP) at punctae moving in anterograde direction along cytonemes (white arrowheads show trajectory in time-lapse frames).",
    "ncbi_link": "GFP: 
Ptc: 35851"
  },
  {
    "caption": "G) Confocal imaging of receiving cells expressing the HA tagged Tsp96F construct also shows co-localization with endogenous Ptc at cytonemes (yellow arrows indicate Tsp96F-HA and Ptc co-localizing punctate structures).",
    "ncbi_link": "HA: 
Tsp96F: 43127"
  },
  {
    "caption": "H) Western blot against HA-tag of Immuno-Precipitated sample (IP), Depleted Sample (Dep), High Speed Sample (HSS) Whole Sample and Control sample from a co-immunoprecipitation experiment isolating GFP of Tsp96F-HA and Ptc-GFP expressing larvae or GFP and Tsp96F-HA expressing larvae as negative control. Arrowhead indicates the positive band corresponding to Tsp96F-HA expected molecular weight (30-40 kDa), present in all samples including the immuno-precipitated one and not present in the negative control sample.",
    "ncbi_link": "GFP: 
HA: 
Tsp96F: 43127"
  },
  {
    "caption": "E) Effect on EV-associated Ptc secretion after gene silencing on Cl8 cells by dsRNAs against the SNARE proteins Syb and α-Snap, the tetraspanin Tsp96F and the ESCRT components Hrs, Tsg101, Shrub and Vps4. Hsp70 in cells and EVs is detected by different exposition time.",
    "ncbi_link": "α-Snap: 40233
Hrs: 33458
Shrub: 35933
Syb: 36080
Tsg101: 39881
tetraspanin: 43127
Tsp96F: 43127
Vps4: 32777"
  },
  {
    "caption": "A) Projection images of three confocal sections (1 μm) at the basal side of wing discs expressing the Bac constructs for Hh-GFP and Ptc-cherry, used to analyse co-localization between the ligand and the receptor in wild type conditions and after inhibition of vesicle fusion (Syb RNAi), vesicle trafficking (Hrs RNAi) or Ptc protein degradation (Dor RNAi). Boxplot shows co-localization rates using the Manders coefficient for proportion of red covered by green in projected images for wing discs temporally expressing RNAi against ESCRT proteins Hrs and Vps4, SNAREs Syb and α-Snap, and Dor as control for effects after Ptc degradation-blocking, as well as temporally over-expressing the Tsp96F-HA. Central horizontal lines show median values of N=8-12 box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding. Note the significant reduction in co-localization rates (1= total coverage of red by green) after RNAi expression for both ESCRT and SNARE proteins as well as after Tsp96F-HA over-expression, while RNAi expression for Dor presents greater co-localization.",
    "ncbi_link": "Bac: 
HA: 
α-Snap: 40233
Dor: 38543
Hrs: 33458
Syb: 36080
Tsp96F: 43127
Vps4: 32777"
  },
  {
    "caption": "B) Projection images of three confocal sections (1 μm) from the apical side of the wing discs. Quantification of co-localization rates using apical projection images; central horizontal lines show median values of N=8-12 , box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. Note that at the apical side no clear significant reduction in co-localization rates (1= total coverage of red by green) is observed after RNAi expression or in Tsp96F-HA over-expression.",
    "ncbi_link": "HA: 
Tsp96F: 43127"
  },
  {
    "caption": "C) Correlation coefficients between the maximum value of quantified integrated density (integrating both fluorescence intensity and signal area) for Ptc-GFP values (Yac construct) and distance from the basal side (-1=basal, +1=apical). Box plot shows quantification data of discs after RNAi expression for the vacuole sorting protein Dor (necessary for Ptc degradation), the ESCRT Hrs, the SNARE Syb as well as after over-expression of the Tsp96F-HA construct and wild type condition. Central horizontal lines show median values of N=8-12, box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. Note the apical localization of Ptc-GFP highest values after degradation impairment (Dor RNAi) in contrast to the basal shift resulting from exocytosis deficiency (Syb RNAi).",
    "ncbi_link": "HA: 
Dor: 38543
Hrs: 33458
Syb: 36080
Tsp96F: 43127"
  },
  {
    "caption": "A) Confocal images at the lateral plane showing the immunostaining of the medium threshold Hh target Collier (Col) of wild type wing discs and discs after inhibition of vesicle fusion (α-Snap RNAi), vesicle trafficking (Hrs RNAi) or in over-expression of the Tsp96F-HA. Quantification of gradient lengths (μm) using Collier signal and normalized to the wing pouch size, showing the proportion of wing pouch covered by signal (1=total coverage). Quantification was performed for wild type condition as well as in temporally regulated RNAi expression for the ESCRT complex proteins Hrs, Tsg101, Shrub and Vps4 and for the SNARE proteins Syb, Snap24, α-Snap, as well as in transient over-expression of the Tsp96F-HA. Central horizontal lines show median values of N=7-22 , box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. Note a slight but significant increase in the length of Col signal for all treatment compared to the wild type condition.",
    "ncbi_link": "HA: 
α-Snap: 40233
Hrs: 33458
Shrub: 35933
Snap24: 41193
Syb: 36080
Tsg101: 39881
Tsp96F: 43127
Vps4: 32777"
  },
  {
    "caption": "B) Lateral confocal images and quantification of the extension of immuno-labeled Engrailed as the high threshold Hh target. Quantification shows number of cell diameters covered by signal from the posterior/anterior border marked by Hh-GFP (Bac construct); central horizontal lines show median values of N=6-10 box shows lower and upper quartiles and the whiskers show the maximum and minimum excluding outliers. Note a significant reduction after RNAi expression, suggesting Hh reception impairment and flattening of the signal gradient.",
    "ncbi_link": "Hh: 42737"
  },
  {
    "caption": "C) Lateral confocal images and quantification of Ptc transcription as a Hh target through immunolabeling of the reporter β−galactosidase (Ptc-LacZ). Middle graph shows the extension covered by signal normalized to wing pouch size, in wild type condition (N=6) or after ectopic expression of the Tsp96F-HA construct (N=9). Green shaded areas show data variability and dotted line gives the average values. Note the greater distance covered after Tsp96F-HA transient expression. Boxplot (right) shows distance quantifications with central horizontal lines showing median values of N=6-9 , box showing lower and upper quartiles and whiskers showing the maximum and minimum excluding outliers. Note a significant extension under Tsp96F-HA expression, suggesting again flattening of the signal gradient.",
    "ncbi_link": "HA: 
LacZ: 
β−galactosidase: 
Ptc: 35851
Tsp96F: 43127"
  },
  {
    "caption": "(B, C) (B) Growth inhibition  assay of  E. coli DH10B  cells harbouring pTrc200 vector or each of its derivatives expressing Tde1  variants with IPTG  induction. (C) Growth inhibition assay of E. coli  DH10B   cells co-expressing the Tde1 variants expressed from pTrc200 plasmid and Tdi1 immunity gene expressed from pRL662 plasmid. Growth  curve was determined at OD600. Graphs of panels B and C show mean ± SD of three biological replicates (n=3), each averaged with 3 technical repeats. One way ANOVA was used for the analysis of statistical significance followed by the Tukey's multiple comparison. Different letters indicate statistically different groups of strains (p value, 4.6x10-5 and 5.19x10-8 for panels B and C respectively).",
    "ncbi_link": "Tde1: 
Tdi1: "
  },
  {
    "caption": "(A) Growth inhibition assay of E. coli DH10B  cells harbouring pTrc200 vector or each of its derivatives expressing Tde1  variants with IPTG  inducible expression. The growth  of  E. coli  was monitored by CFU counting every 1 hr. Data information: Graphs of panels A, show mean ± SD of three biological replicates (n=3), each averaged with 3 technical repeats. One way ANOVA was used for the analysis of statistical significance followed by the Tukey's multiple comparison.",
    "ncbi_link": "Tde1: "
  },
  {
    "caption": "For  membrane permeabilization  assays, BW25113  WT alone or ∆lacY(pYTA-lacZ) cells harbouring pTrc200 vector or each of its derivatives expressing Tde1  variants were carried out for (C) propidium iodide permeability   with cells treated with Propidium iodide  and Hoechst  for detection by fluorescence microscope (Scale bar = 5 μm). For quantification of cells with PI  signals, a total of 6 randomly selected images obtained from two biological repeats were used to quantify the number of PI-stained  cells / number of Hoechst-stained  cells as indicated.",
    "ncbi_link": "lacY: 
Tde1: 
lacZ: 945006"
  },
  {
    "caption": "(D) Bacteriostatic activity assay. E. coli DH10B  cells harbouring pTrc200 vector or each of its derivatives expressing Tde1  variants were cultured with or without IPTG  induction for 1 hr. The IPTG-induced cells were further centrifuged and resuspended in the fresh medium with or without IPTG. Cell density was measured again before continuous growth  for additional 1 hr. Data information: Graphs of panels show mean ± SD of three biological replicates (n=3), each averaged with 3 technical repeats. One way ANOVA was used for the analysis of statistical significance followed by the Tukey's multiple comparison. Different letters indicate statistically different groups of strains (p value, 1×10-16 and 2×10-16 for panels D respectively).",
    "ncbi_link": "Tde1: "
  },
  {
    "caption": "(A) Co-immunoprecipitation (Co-IP) in A. tumefaciens. A. tumefaciens C58 ∆tde1 harbouring pTrc200 vector or its derivatives expressing HA-tagged Tde1  variants. Anti-HA  resin was used to coprecipitate the Tde1  variants and Tap1.",
    "ncbi_link": "HA: 
tde1: 
Tde1: "
  },
  {
    "caption": "(B) Secretion assay for HA-tagged Tde1  variants. Western blot  for the cellular  and extracellular  fractions of A. tumefaciens C58 ∆tdei and ∆tdei∆tssK expressing the HA-tagged Tde1  variants. Hcp  secretion was detected as a positive control for active T6SS  secretion. Representative western blot results of three biological repeats were shown with antibody against HA, Hcp, or EF-Tu where EF-Tu serve as a loading and non-secreted protein control. Protein markers are indicated in kDa.",
    "ncbi_link": "HA: 
Tde1: 
tssK: "
  },
  {
    "caption": "(A)  Fluorescence microscopy for Tde1 translocation.  A. tumefaciens C58 ∆tdei  expressing Tde1  variants fused with sfGFP  (in green) and  E. coli DH10B  carrying mCherry  (false coloured in blue) were co-cultured for 20 hrs. A cyan fluorescence with merged blue and green signals represented the translocation  of Tde1  variants from  A. tumefaciens  to  E. coli (Scale bar = 5 μm).",
    "ncbi_link": "mCherry: 
sfGFP: 
Tde1: "
  },
  {
    "caption": "(A) Interbacterial competition of A. tumefaciens C58 ∆tdei and ∆tdei∆tssK expressing the Tde1  variants against E. coli cells was carried out on LB medium and E. coli survival rate was quantified by CFU counting. (B) Interbacterial competition  between various A. tumefaciens C58  strains and A. tumefaciens 1D1609 on AK medium and the competition outcome was shown by competitive index. Data information: Data in panel A are mean ± SD of four biological repeats of two independent experiments (n=4). Panels B show mean ± SD of three biological repeats (n=3). One way ANOVA was used for the analysis of statistical significance followed by the Fishers Least Significant Difference (LSD) test for panel A and B Different letters indicate statistically different groups of strains (p value, 3.63×10-4, 2.70 × 10-3, 2.3 × 10-15 for panels A, B respectively).",
    "ncbi_link": "Tde1: 
tssK: "
  },
  {
    "caption": "(C) Secretion assay for Tde1  and its variants co-expressed with its immunity protein Tdi1  in  A. tumefaciens C58 ∆tdei and ∆tdei∆tssK. Data information:  Western blots were detected with specific antibody against Tde1, Hcp, or EF-Tu serving as a loading and non-secreted protein control. Protein markers are indicated in kDa. Results in panel C are representative of three biological repeats.",
    "ncbi_link": "Tde1: 
tssK: "
  },
  {
    "caption": "(C) The upregulation of NOD2 gene expression was assessed by quantitative PCR. The results are depicted as the mean fold change in NOD2 gene expression relative to unstimulated cells (n = 11).",
    "ncbi_link": "NOD2: 64127"
  },
  {
    "caption": "LL37 and IRGM gene expression is upregulated following NOD2 activation (A‐D). Alveolar macrophages were incubated in the presence of 10 μg/mL of MDP or 100 ng/mL of LPS for 24 h. Upregulation of (A) LL37 and (D) IRGM gene expression was assessed after specific ligand recognition by quantitative PCR using the Taqman system and the ΔΔCT method for relative quantification. The fold change in gene expression relative to unstimulated cells is depicted. Data are representative of two independent experiments (n = 7-12). Bold lines indicate median values.",
    "ncbi_link": "LL37: 820
IRGM: 345611
NOD2: 64127"
  },
  {
    "caption": "(E) LL37 and (F) IRGM gene expression was assessed by quantitative PCR using the Taqman system and the ΔΔCT method for relative quantification. Fold changes in gene expression relative to unstimulated cells are reported. Bold lines indicate median values of n = 9. *p 0.05 and **p 0.01 using the two‐tailed Wilcoxon signed‐rank test.",
    "ncbi_link": "LL37: 820
IRGM: 345611"
  },
  {
    "caption": "mRNA expression of individual patients normalized to 18S-rRNA and relative to a pooled organ donor sample. Lines between dots connect samples from the same patient. CP: chronic pancreatitis; PDAC: pancreatic ductal adenocarcinoma; significant difference (P < 0.05) between tumor and normal tissue P = 9.39 × 10−5 determined by paired two-tailed Student's t-test, n = 17 patients.",
    "ncbi_link": "18S: "
  },
  {
    "caption": "Association of microarray-based TBL1 expression and survival in 105 patients with PDAC: High TBL1 expression is significantly associated with shorter post-resection survival. P-value determined by log-rank test as described in Materials and Methods.",
    "ncbi_link": "TBL1: 6907///90665"
  },
  {
    "caption": "Immunohistochemistrystaining for TBL1 in paraffin-embedded tissue sections of wild-type or p48+/Cre; Kras+/LSL-G12Dmice. 1, 2: healthy tissue with acini, islet of Langerhans, and duct (zoom-in in panel 2) showing occasional weak nuclearstaining. 3, 4: PanIN-1 lesions with nuclearstaining. 5, 6: PanIN-2 lesions with nuclearstaining. 7, 8: PanIN-3 lesion with nuclearstaining. 9-12: invasive pancreatic ductal adenocarcinoma cells with nuclear and occasional faint cytoplasmicstaining. Scale bars: 100 μm. Images are representative of 32 wild-type and 29 p48+/Cre; Kras+/LSL-G12Dmice.",
    "ncbi_link": "p48: 16391
Kras: 16653"
  },
  {
    "caption": "Left panel: EdU incorporation in siRNA-transfected Capan-1 cells (72 h post-transfection), n = 6 cell culture wells per group; significantly different (P < 0.05) from control (no siRNA) *, siNC #1 #, siNC #2 $; P-values: siTBL1#1 8.24 × 10−4 (*), 5.43 × 10−4 (#), 7.93 × 10−6 ($); siTBL1 #2 1.66 × 10−11 (*), 1.27 × 10−11 (#), 8.79 × 10−13 ($), one-way ANOVA with Bonferroni post-test. Right panel: EdU incorporation of Panc02 cells with stable expression of shRNA; n = 6 cell culture wells per group; significantly different (P < 0.05) from control (shNC) #P = 0.0398; Welch's t-test.",
    "ncbi_link": "TBL1: 6907///90665"
  },
  {
    "caption": "Cellgrowth of siRNA-transfected Capan-1 or Panc8680 cells; n = 3 cell culture wells per group; significantly different (P < 0.05) from control (no siRNA) *, siNC #1 #, siNC #2 $; P-values: Capan-1 cells 48 h time-point: 0.0408 (*) for siTBL1 #1 / 0.0464 for siTBL1 #2, Capan-1 cells 72 h time-point: 8.60 × 10−5 (*), 1.82 × 10−3 (#), 3.24 × 10−5 ($) for siTBL1 #1 / 2.39 × 10−10 (*), 3.34 × 10−9 (#), 1.08 × 10−10 ($) for siTBL1 #2; Panc8680 72 h time-point: 1.55 × 10−4 (*), 2.73 × 10−5 ($); two-way ANOVA with Bonferroni post-test.",
    "ncbi_link": "TBL1: 21372
TBL1: 6907///90665"
  },
  {
    "caption": "Chromatin immunoprecipitation from Capan-1 cells with or without siRNA-mediated knockdown of TBL1. IgG and primers for PIK3CA coding region served as a negative control; histone H3 served as a positive control.",
    "ncbi_link": "PIK3CA: 5290
TBL1: 6907///90665"
  },
  {
    "caption": "Proliferation time course assay in control and TBL1 shRNA-transfected Panc02 cells overexpressing constitutively active PI3K p100α mutant E545K. Cells were stained with crystal violet, and absorbance was measured at 595 nm. n = 9 cell culture wells per group; statistically significant at P < 0.05 for indicated comparisons: shNC pBabe-puro vs. shNC pBabe-PI3K (*), shTBL1 pBabe-puro vs. sbTBL1 pBabe-PI3K (#), shNC pBabe-puro vs. shTBL1 pBabe-puro ($), shNC pBabe-PI3K vs. shTBL1 pBabe-PI3K (†); P-values: day 2: 2.01 × 10−3 (#), 4.11 × 10−9 ($), 5.77 × 10−3 (†); day 3: 4.50 × 10−5 (*), 1.01 × 10−9 (#), 1.71 × 10−30 ($), 1.22 × 10−6 (†); day 4: 5.61 × 10−22 (*), 1.10 × 10−45 (#), 6.65 × 10−62 ($); two-way ANOVA with Bonferroni post-test.",
    "ncbi_link": "PI3K: 18708
TBL1: 21372"
  },
  {
    "caption": "mRNA expression of PIK3CA in human patient samples; significant difference (P < 0.05) between tumor and normal tissue *P = 2.13 × 10−4 determined by paired two-tailed Student's t-test, n = 18 patients.",
    "ncbi_link": "PIK3CA: 5290"
  },
  {
    "caption": "Correlation of mRNA expression of TBL1 and PIK3CA in human patient tumor tissue (normalized to 18S rRNA and relative to a pooled organ donor sample); n = 17 patients; P-value determined by testing for slope of regression line ≠ 0.",
    "ncbi_link": "18S: 
PIK3CA: 5290
TBL1: 90665///6907"
  },
  {
    "caption": "Survival analysis in 105 patients with PDAC: High PIK3CA expression is significantly associated with shorter post-resection survival. P-value determined by log-rank test as described in Materials and Methods.",
    "ncbi_link": "PIK3CA: 5290"
  },
  {
    "caption": "A-D Panc02 cells with stable expression of luciferase were implanted subcutaneously into C57Bl6/N mice. Six days later, tumors were injected three times per week with 108 ifu of adenovirus encoding shRNA. (A-C): Data plotted as mean ± SEM; n = 4 animals in control (shNC) group and n = 3 animals in knockdown (shTBL1) group; significantly different (P < 0.05) between control (shNC) and knockdown (shTBL1) *. (A) Tumor volume determined by transcutaneous measurement with digital calipers; P-values: 9.21 × 10−3 at day 15, 6.02 × 10−4 at day 18, 2.49 × 10−4 at day 20; two-way ANOVA with Bonferroni post-test. (B) Luminescence of tumors after intraperitoneal injection of firefly d-luciferin; P = 0.0133 at day 20; two-way ANOVA with Bonferroni post-test. (C) Tumor mass at necropsy; P = 0.0299, one-sided Welch's t-test. (D) Luminescence images of one representative mouse in each group.",
    "ncbi_link": "TBL1: 21372"
  },
  {
    "caption": "TBL1-depletion leads to reduction in PI3 kinase p110α and cell cycle-associated proteinsPanc02 cells with stable expression of shRNA were implanted subcutaneously into C57Bl6/Nmice. Seven days later, mice were treated with 20 mg/kg gemcitabine delivered by intraperitoneal injection. After 21 days, mice were sacrificed, tumors were removed and proteins were extracted and immunoblotted.",
    "ncbi_link": "TBL1: 21372"
  },
  {
    "caption": "A-D Appearance of autophagic structures (marked with GFP-Atg8a) during wound closure in the epidermis of control third instar larvae and after epidermal knockdown of the autophagy pathway components Atg1, Atg5, Atg6, Atg7 or Atg12. All constructs are expressed in the epidermis under the control of the A58-Gal4 driver. (A) Time points from movies of wounded epidermis. The wounds have closed by 2 h in all cases. (B) Higher magnification of the areas marked by magenta boxes at t=120 min. (C) Quantification of the appearance of GFP-Atg8a puncta in the imaged area (10000 µm2) 3 control larvae, shown for each individual larva. (D) Quantification of number of GFP-Atg8a puncta in different genetic conditions measured in an area of 10000 µm2 at the time of wound closure; n=4-10 larvae each genotype, for the detail see Data analysis.",
    "ncbi_link": "A58: 2845988
Atg1: 39454
Atg12: 39383
Atg5: 31666
Atg6: 42850
Atg7: 37141
Gal4: 855828"
  },
  {
    "caption": "Control of epidermal autophagy by TOR signalling. (A) Epidermis of third instar larvae expressing the autophagosome marker GFP-Atg8a together with constructs for up- or down-regulating the autophagy pathway in the epidermis. Healthy epidermis contains few autophagosomes, but artificially activating autophagy through overexpression of Atg1 or blocking TOR signalling leads to accumulation of autophagosomes. (B) Higher magnification of the areas marked by magenta boxes in (A).",
    "ncbi_link": "Atg1: 39454
TOR: 47396"
  },
  {
    "caption": "A-D Fluorescence loss in photobleaching (FLIP) to test free cytoplasmic GFP motility within the epidermis. A small area (magenta circle; 179 or 1098 µm2) was laser-illuminated for the indicated times (3 or 20 min) in control or Atg1-expressing epidermis also expressing free GFP. (A) Snapshots before bleaching and at 3 points of recovery. (B) Kymographs along the broken line in (A) during recovery. (C, D) Quantification of fluorescence recovery after bleaching, shown separately for 3 and 20 min bleaching protocols.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "B-D Atg1-induced syncytium formation is abolished when Atg5 function is downregulated (compare to rows 2 and 3 in Fig. 5A, B); same representation as shown in Fig. 5A-D.",
    "ncbi_link": "Atg1: 39454
Atg5: 31666"
  },
  {
    "caption": "(A) After randomized, 8-12 weeks old and sex-matched Phb1F/F mice  and Phb1MyeKO mice  were administered with PBS  or LPS  (30 mg/kg) for 12 hours via intraperitoneal injection. Serum  was collected and ELISA  assays were used to detect the level of  IL-1β (n = 6, 10, 6, and 12 mice  for each group, respectively). Data presented as mean ± SEM. * p < 0.05, ** p < 0.01, **** p< 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(B) BMDMs  were extracted from  Phb1F/F or Phb1MyeKO mice  and stimulated by 20% culture supernatant  of L929  cells for 7 days. Differentiated BMDMs  were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes, the cells were lysed and the culture medium was collected. Western blotting (WB) assays were used to detect protein levels in whole cell lysates (Lys) and  culture medium (Sup).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(C) BMDMs  were extracted from  Phb1F/F or Phb1MyeKO mice and stimulated with 20% culture supernatant of L929  cells for 7 days. Differentiated BMDMs  were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. ELISA  assays were used to detect protein levels in the culture medium. Data of BMDMs  from the separate mice  (n = 6 mice  for each group) and are presented as mean ± SEM. *** p < 0.001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(D) After randomized, 4 weeks old and sex-matched Phb1F/F mice  and Phb1MyeKO mice  were administered with PBS  or LPS  (300 mg/kg) to induce septic  shock via intraperitoneal injection. The life span of  Phb1F/F mice  (n = 6) and Phb1MyeKO mice  (n = 7) was recorded.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(J) After  J774A.1 cells with Phb1  or Phb2  knockdown were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes, the cells were lysed, and the culture medium was collected. Protein levels in whole cell lysates (Lys) and culture medium (Sup) were detected by WB  assays.",
    "ncbi_link": "Phb1: 18673
Phb2: 12034"
  },
  {
    "caption": "(K) After J774A.1 cells with Phb1  or Phb2  knockdown were stimulated with LPS (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes, the culture medium was collected. ELISA  assays were used to detect IL-1β  levels in the culture medium. Data are from three independent experiments (mean ± SEM). n.s., no significance, **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673
Phb2: 12034"
  },
  {
    "caption": "(A-B) GFP-expressing HeLa  cells with stable Phb1  knockdown were fixed and subjected to immunofluorescence  (IF) analysis to detect mitochondria  (MitoTracker, red; A) or ΔΨm  (TMRM, red; B). Images shown are representative of at least three independent experiments. White boxed regions in the panels in (A) are enlarged. Scale bar: 10 μm.",
    "ncbi_link": "GFP: 
Phb1: 5245"
  },
  {
    "caption": "(C)  Flow cytometric  analysis of ΔΨm  (TMRM). HeLa  cells with stable Phb1  knockdown were treated with CsA  (2 μM) for 30 minutes or FCCP  (4 μM) for 5 minutes.",
    "ncbi_link": "Phb1: 5245"
  },
  {
    "caption": "(D) The mitochondrial  respiratory capacity of  J774A.1 cells with or without Phb1  knockdown was measured with a Seahorse XFe96 analyzer. Data are from at least three independent experiments (mean ± SEM). n.s., no significance. ** p < 0.01, *** p < 0.001, **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(E) HeLa  cells with stable PHB1  ablation were incubated with H2O2 (2 μM) and CsA  (2 μM) for 30 minutes. Flow cytometric analysis of intracellular ROS  levels (DHE).",
    "ncbi_link": "PHB1: 5245"
  },
  {
    "caption": "(F-G) Confocal microscopy analyses of mitochondrial Ca2+ in time-series mode. HeLa  cells stably expressing 4mt-RCaMPh with or without Phb1  knockdown were treated with CsA  (2 μM) for 30 minutes. During acquisition of fluorescence images (F), cells were treated with histamine  (200 μM). Traces of mitochondrial Ca2+ (4mt-RCaMPh) dynamics are shown in (G) (mean ± SEM). n = 16, 16, 15, 16 (from the top to the bottom). Scale bar: 10 μm. * p < 0.05 relative to Scramble group, # p < 0.05 relative to shPHB1 group (Student's t-test).",
    "ncbi_link": "Phb1: 5245
PHB1: 5245"
  },
  {
    "caption": "(A) The  co-localization between mtDNA  (SG-ALK, green) and mitochondria  (MitoTracker, red) was examined in J774A.1 cells with or without knockdown of Phb1  or Phb2. White boxed regions in the panels are enlarged. The white arrows indicate mtDNA  outside mitochondria. Scale bar: 10 μm. (B) Quantitative analysis of data from (A). Data are from ten, eight, and seven images from three independent experiments (left to right, respectively) (mean ± SEM). n.s., no significance, *** p < 0.001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673
Phb2: 12034"
  },
  {
    "caption": "(C)  J774A.1 cells with or without Phb1  knockdown were lysed, and DNA was extracted. qPCR  assays were used to detect the mtDNA  levels (D-loop) in the cytosol  relative to nuclear  DNA levels (Tert) in the whole cell lysates. Data are from six independent experiments (mean ± SEM). **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673
Tert: 21752"
  },
  {
    "caption": "(D) BMDMs  isolated from Phb1F/F mice  and Phb1MyeKO mice  were fixed and subjected to IF  analysis to detect the co-localization between mitochondria  (MitoTracker, red) and mtDNA (SG-ALK, green). White boxed regions in the panels are enlarged. The white arrows indicate mtDNA  outside mitochondria. Scale bar: 10 μm. (E) Quantitative analysis of data from (D). Data are from ten and eight images from three independent experiments (mean ± SEM). ** p < 0.01 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(F) PBMCs  were extracted from Phb1F/F mice  and Phb1MyeKO mice. Cells were lysed, and DNA was extracted. qPCR  assays were used to detect the levels of mtDNA (D-loop) in the cytosol  relative to the levels of nuclear  DNA levels (Tert) in the whole cell lysates. Data of PBMC  are from seven  Phb1F/F mice  and Phb1MyeKO mice, respectively (mean ± SEM). ** p < 0.01 (Student's t-test).",
    "ncbi_link": "Phb1: 18673
Tert: 21752"
  },
  {
    "caption": "(G) HeLa  cells expressing TFAM-FLAG  with or without Phb1  knockdown were incubated with CsA  (2 μM) for 30 minutes. Cells were fixed and subjected to IF  analysis to detect the  co-localization between mitochondria  (anti-TOMM20, red) and TFAM-FLAG  (anti-FLAG, green). White boxed regions in the panels are enlarged. The white arrows indicate mtDNA  outside mitochondria. The yellow arrows indicate mtDNA  inside mitochondria. Scale bar: 10 μm.",
    "ncbi_link": "FLAG: 
Phb1: 5245
TFAM: 7019"
  },
  {
    "caption": "(I) HeLa  cells with or without Phb1  knockdown were incubated with H2O2 (5 mM) for 20 minutes and CsA  (4 μM) for 12 hours. Cells were lysed, and DNA was extracted. qPCR assays were used to detect mtDNA  levels (ND1) in the cytosol  and nuclear  DNA levels (18S) in the whole cell lysates. Data are from four independent experiments (mean ± SEM). ** p < 0.01, *** p < 0.001, **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "18S: 
ND1: 4535
Phb1: 5245"
  },
  {
    "caption": "HeLa  cells with or without Phb1  knockdown were incubated with VBIT-4 (10 μM) for 1 hour and subsequently lysed, and DNA was extracted. qPCR  assays were used to detect mtDNA  levels (ND1  in HeLa  cells in the cytosol  relative to nuclear  DNA levels (TERT  in HeLa  cells in the whole cell lysates. Data are from three independent experiments (mean ± SEM). n.s., no significance, * p < 0.05, ** p < 0.01, *** p < 0.001 (Student's t-test).",
    "ncbi_link": "ND1: 4535
Phb1: 5245
TERT: 7015"
  },
  {
    "caption": "J774A.1 cells with or without Phb1  knockdown were incubated with VBIT-4 (10 μM) for 1 hour and subsequently lysed, and DNA was extracted. qPCR  assays were used to detect mtDNA  levels D-loop  in J774A.1 cells) in the cytosol  relative to nuclear  DNA levels Tert  in J774A.1  cells) in the whole cell lysates. Data are from three independent experiments (mean ± SEM). n.s., no significance, * p < 0.05, ** p < 0.01, *** p < 0.001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673
Tert: 21752"
  },
  {
    "caption": "(L)  J774A.1  cells with or without Phb1  knockdown were lysed. The whole cell lysates were immunoprecipitated  by IgG or anti-ASC  antibody and the resulting proteins were detected by WB  assay.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(M) BMDMs  isolated from  Phb1F/F mice  and  Phb1MyeKO mice  were incubated with MCC950  (50 nM) for 30 mins and were subsequently stimulated by LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. Protein levels in whole  cell lysates and culture medium  were detected by WB  assay.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(A) BMDMs  isolated from  Phb1F/F mice  and Phb1MyeKO mice  were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. Cells were fixed and subjected to IF  analysis to detect the co-localization between NLRP3  (anti-NLRP3, red) and mtDNA  (PicoGreen, green). White boxed regions in the panels are enlarged. The white arrows indicate mtDNA co-localized with NLRP3. Scale bar: 10 μm. (B) Quantitative analysis of data from (A). Data are from at least 14 images from three independent experiments (mean ± SEM). **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(C) J774A.1  cells with or without Phb1  knockdown were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. Cells were fixed and subjected to IF  analysis to detect the co-localization  between NLRP3  (anti-NLRP3, red) and mtDNA  (PicoGreen, green). White boxed regions in the panels are enlarged. The white arrows indicate mtDNA co-localized  with NLRP3. Scale bar: 10 μm.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(E) J774A.1 cells with or without Phb1  knockdown were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. After cells were lysed, NLRP3  was immunoprecipitated  by anti-NLRP3  antibody. mtDNA  levels (D-loop) from immunoprecipitants were detected by qPCR in J774A.1 cells with or without Phb1  knockdown. Data are from five independent experiments (mean ± SEM). ** p < 0.01, **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(F) J774A.1 cells with Phb1  knockdown were incubated with EtBr  (150 ng/ml) for 3 days, followed by LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. WB  was used to detect the protein levels in whole cell lysates  and culture medium.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(G) BMDMs  isolated from Phb1F/F mice  and Phb1MyeKO mice were treated with NAC  (2 mM) for 8 hours, LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. WB  assay was used to detect the protein levels in whole cell lysates and in the culture medium.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "HeLa  cells with or without Phb1  knockdown were lysed. The whole cell lysate was immunoprecipitated  by IgG, anti-AFG3L2  antibody or anti-SPG7  antibody. The respective levels of precipitated SPG7  or AFG3L2  were examined by WB.",
    "ncbi_link": "Phb1: 5245"
  },
  {
    "caption": "J774A.1  cells with or without Phb1  knockdown were lysed. The whole cell lysate was immunoprecipitated  by IgG, anti-AFG3L2  antibody or anti-SPG7  antibody. The respective levels of precipitated SPG7  or AFG3L2  were examined by WB.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "(A) J774A.1 cells with knockdown of Phb1  alone, Afg3l2  alone, Spg7  alone, Phb1   + Afg3l2, or Phb1  + Spg7  were fixed and subjected to IF  analysis to assess the  co-localization  between mitochondria  (MitoTracker, red) and mtDNA  (PicoGreen, green). White boxed regions in the panels are enlarged. The white arrows indicate mtDNA  outside mitochondria. Scale bar: 10 μm. (B) Quantitative analysis of the data from (A). Data are from at least 12 images from three independent experiments (mean ± SEM). ** p < 0.01, **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Afg3l2: 69597
Phb1: 18673
Spg7: 234847"
  },
  {
    "caption": "(C) J774A.1 cells with knockdown of Phb1  alone, Afg3l2  alone, Spg7  alone, Phb1  + Afg3l2, or Phb1  + Spg7  were lysed, and DNA was extracted. qPCR  was used to detect the mtDNA  levels (D-loop) in the cytosol  relative to the nuclear  DNA levels (Tert) in the whole cell lysate. Data are from six independent experiments (mean ± SEM). **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Afg3l2: 69597
Phb1: 18673
Spg7: 234847
Tert: 21752"
  },
  {
    "caption": "(D)  J774A.1 cells with knockdown of Phb1  alone, Afg3l2  alone, Spg7  alone, Phb1 + Afg3l2, or Phb1  + Spg7  were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. The culture medium was collected and ELISA  assays were used to detect IL-1β levels in culture medium. Data are from four independent experiments (mean ± SEM). **** p < 0.0001 (Student's t-test).",
    "ncbi_link": "Afg3l2: 69597
Phb1: 18673
Spg7: 234847"
  },
  {
    "caption": "(E)  J774A.1 cells with Phb1  knockdown, Spg7  knockdown, or combined Phb1  and Spg7  knockdowns were stimulated with LPS  (200 ng/ml) for 6 hours and ATP  (4 mM) for 45 minutes. WB  assay was used to detect the protein levels in whole cell lysates and culture medium.",
    "ncbi_link": "Phb1: 18673
Spg7: 234847"
  },
  {
    "caption": "(F) J774A.1   cells with Phb1   knockdown, Afg3l2   knockdown, and combined Phb1   and Afg3l2   knockdowns were stimulated with LPS   (200 ng/ml) for 6 hours and ATP   (4 mM) for 45 minutes. WB   assay was used to detect the protein levels in whole  cell lysates  and culture medium.",
    "ncbi_link": "Afg3l2: 69597
Phb1: 18673"
  },
  {
    "caption": "(H) J774A.1 cells with or without Phb1  knockdown were lysed. The whole cell lysates were immunoprecipitated  by IgG or anti-SPG7  antibody. WB  was used to detect the CYPD  and VDAC  levels in the precipitated products.",
    "ncbi_link": "Phb1: 18673"
  },
  {
    "caption": "A. SDS-PAGE analysis of the D391N DIS3L2-RNA complexes. RNAs were radioactively labeled at the 5' end and DIS3L2-bound RNAs were detected by autoradiography. The negative control was performed with HEK293T-Rex cells (Control)",
    "ncbi_link": "DIS3L2: 129563"
  },
  {
    "caption": "F. Secondary structure of pre-hsa-let-7i, with both 5p and 3p mature products highlighted in bold. The intramolecular ligation position is indicated in dash line between nt 28 and 61. It corresponds to cleavage positions of RNaseT1, which leaves 3'-terminal guanosine residues.",
    "ncbi_link": "hsa-let-7i: 406891"
  },
  {
    "caption": "G. D391N DIS3L2 overexpression does not cause abundance changes of CLIPed uridylated RNAs. Scatter plot of transcript abundances estimated from RNA-seq from the cell line overexpressing D391N DIS3L2 and control HEK293T-Rex cells. CLIPed transcripts are marked in white.",
    "ncbi_link": "DIS3L2: 129563"
  },
  {
    "caption": "B. U+ read coverage in downstream regions of mature U12 snRNA, Vault1 and 7SL ncRNAs. The full dark box is representing mature ncRNA, the thin line indicates the region downstream of the mature 3' end (extension).",
    "ncbi_link": "U12: 26823"
  },
  {
    "caption": "C. Quantification of DIS3L2 D391N RIP analysis of U12 and U5D snRNAs showing number of snRNA clones with mature (Mat), extended (ext) or trimmed (Trim) 3' end. +U is number of clones with untemplated 3' oligo(U) ends. For more details see Figure S2. (D) An example of hybrid reads (produced by intra-strand ligation of RNaseT1 products during CLIP protocol) for RNU5D snRNA.",
    "ncbi_link": "DIS3L2: 129563
U12: 26823
RNU5D: 100873841///26830
U5D: 100873841///26830"
  },
  {
    "caption": "C. Northern blot analysis of RNAs immunoprecipitated with Flag-tagged WT (DIS3L2) and D391N (MUT) DIS3L2, AGO2 and DIS3, respectively. The blots were probed with radioactively labeled probes for 5' and 3' ends of mature tRNAVal, respectively.",
    "ncbi_link": "AGO2: 27161
DIS3: 22894
DIS3L2: 129563"
  },
  {
    "caption": "C. The uridylated aberrant RNAs are stabilized in cells with nonfunctional DIS3L2. Small RNAs were modified with 3' end linker, and linker-specific primer was used for cDNA synthesis. Uridylated RNAs were PCR amplified in a semi-quantitative way with the same amount of input RNA used for RT reaction. We used a combination of the gene- and linker-specific primers, -RT ctrl is RT-PCR control, where no reverse transcriptase was added; PCR control is a reaction with no cDNA added. The graph on the right summarizes the percentage of uridylated and nonuridylated 5' fragments of OAT mRNA in HEK293T-Rex cells (Ctrl) and cells overexpressing mutant DIS3L2 (D391N).",
    "ncbi_link": "DIS3L2: 129563
OAT: 4942"
  },
  {
    "caption": "D. DIS3L2-bound uridylated RNAs are degraded by DIS3L2 in vivo. RT-PCR amplification of 5'mRfs of OAT and RPL12 genes and 3' extended forms of U12 snRNA (RNU12 ext) from HEK293T cell lines with modified expression of DIS3L2 (as marked on top) was performed as described in C. Regions of mature 5S rRNA and 7SL RNA were used as loading controls. DIS3L2 KO is a DIS3L2 knock-out cell line. DIS3L2 rescue is DIS3L2 KO cells with stably integrated mutant (D391N) and wild type (WT) DIS3L2 expressing constructs, respectively. Bands marked with * are unspecific primer-dimer PCR products.",
    "ncbi_link": "5S: 
7SL: 
DIS3L2: 129563
OAT: 4942
RNU12: 26823
U12: 26823
RPL12: 6136"
  },
  {
    "caption": "E. Metagene analysis of the position of DIS3L2 D391N clipped U+ reads peak maximum around mRNA transcription start sites (TSS) and of the ChIP-seq data for RNAP II.",
    "ncbi_link": "RNAP II: "
  },
  {
    "caption": "F. U+5'mRfs and aberrant forms of U12 snRNA are highly enriched in the cytoplasm. RT-PCR detection of 5'mRfs of the OAT and RPL12 and aberrant form of U12 snRNA was performed as described in C with RNA isolated from nuclear and cytoplasmic fractions, respectively. The RT-PCR amplification of the body of 5S rRNA was used as a positive control for RNA isolation and RT reaction in both fractions. The identity and uridylation status of cytoplasmic OAT U+5'mRfs was confirmed by sequencing (shown on the bottom). In red are untemplated nucleotides, in green region corresponding to the first intron of OAT pre-mRNA. The efficiency of the subcellular fractionation was monitored by western blot (right panel, WB). DDX5 is nucleoplasmic, ACO2 is mitochondrial, and DIS3L2 and TUBa are cytoplasmic markers.",
    "ncbi_link": "5S: 
OAT: 4942
U12: 26823
RPL12: 6136"
  },
  {
    "caption": "C, D. Scatter plots showing individual recordings of pairs of uninfected and infected neurons in slices expressing shRNA against GSK3α at −60 mV (AMPAR-mediated EPSCs; C) or at +40 mV (NMDAR-mediated EPSCs; D). Error bars represent SEM. Statistical significance was calculated according to the Wilcoxon signed-rank test. E. Quantification of individual (open circles) and average (grey bars) AMPA/NMDA ratios of neurons from uninfected and GSK3α shRNA lentivirus infected slices, where AMPAR-mediated current is taken as the peak response at −60 mV, and NMDAR-mediated current is measured at +40 mV at a latency of 60 ms following stimulation. Error bars represent SEM. Statistical significance was calculated according to the Mann-Whitney U test. ",
    "ncbi_link": "GSK3α: 606496"
  },
  {
    "caption": "Scatter plots showing individual recordings of pairs of uninfected and infected neurons in slices at −60 mV (AMPAR-mediated EPSCs; C) or at +40 mV (NMDAR-mediated EPSCs; D). Error bars represent SEM. Statistical significance was calculated according to the Wilcoxon signed-rank test. Quantification of individual (open circles) and average (grey bars) AMPA/NMDA ratios of neurons from uninfected and infected slices, where AMPAR-mediated current is taken as the peak response at −60 mV, and NMDAR-mediated current is measured at +40 mV at a latency of 60 ms following stimulation. Error bars represent SEM. Statistical significance was calculated according to the Mann-Whitney U test. F, G. As C, D, for GSK3β. Error bars represent SEM. Statistical significance was calculated according to the Wilcoxon signed-rank test. H. As E, for GSK3β. Error bars represent SEM. Statistical significance was calculated according to the Mann-Whitney U test. ",
    "ncbi_link": "GSK3β: 56637"
  },
  {
    "caption": "C. Time course of the peak AMPAR-mediated synaptic response to Schaffer collateral stimulation before, during, and after the induction of LTD by LFS (300 pulses at 1 Hz), in control (uninfected) and GSK3α (blue) or GSK3β (orange) shRNA-expressing neurons. Error bars represent SEM. D. Quantification of average synaptic depression from the last 5 minutes of the time course shown in C. Error bars represent SEM. Statistical significance was calculated according to the Mann-Whitney U test. E. Cumulative frequency distribution of the ESPC values plotted in D. Statistical significance was calculated according to the Kolmogorov-Smirnov test. ",
    "ncbi_link": "GSK3α: 50686
GSK3β: 84027"
  },
  {
    "caption": "B. Representative traces for C-F, showing evoked AMPAR- and NMDAR-mediated EPSCs (collected at −60 mV and +40 mV, respectively) in paired uninfected (black traces) and EGFP-GSK3α- or EGFP-GSK3β -expressing neurons (green traces).",
    "ncbi_link": "EGFP: 
GSK3α: 50686
GSK3β: 84027"
  },
  {
    "caption": "C, D. Scatter plots showing individual recordings of pairs of uninfected and infected neurons at −60 mV (AMPAR-mediated EPSCs) in slices expressing EGFP-GSK3α (C) or EGFP-GSK3β (D). Error bars represent SEM. Statistical significance was calculated according to the Wilcoxon signed-rank test. E, F. Scatter plots showing individual recordings of pairs of uninfected and infected neurons at +40 mV (NMDAR-mediated EPSCs) in slices expressing EGFP-GSK3α (E) or EGFP-GSK3β (F). Error bars represent SEM. Statistical significance was calculated according to the Wilcoxon signed-rank test. ",
    "ncbi_link": "EGFP: 
GSK3α: 50686
GSK3β: 84027"
  },
  {
    "caption": "A. Representative confocal images from EGFP-GSK3α FRAP experiments in organotypic slices cultured from C57 wild-type mice. Upper left panel ('Baseline') shows EGFP-GSK3α expression in a dendrite and dendritic spine. The spine was bleached ('Bleach'; yellow dashed circle) and its fluorescence partially recovered 90 s later ('Recovery'). Single dendritic spines were imaged once per second for 10 seconds prior to, and for 90 seconds following, spine photobleaching. Such single FRAP experiments were performed on different spines during basal conditions ('basal'; upper panels), immediately after cLTD induction with 20 µM NMDA for 5 minutes ('cLTD'; middle panels), and immediately following 10 minutes of washout ('washout'; lower panels). Scale bars = 1 µm. B. Time course of fluorescence recovery during FRAP experiments described in A. White circles ('basal') show the average spine/dendrite fluorescence of FRAP on EGFP-GSK3α-expressing spines in wild-type mouse slices prior to cLTD induction. Pink circles ('cLTD') show fluorescence in spines in which cLTD had been induced using 20 µM NMDA. Green circles ('washout ') represent the average of spine fluorescence after NMDA washout for 10 minutes. Recovery trajectories for the three conditions are fitted with two-phase exponential curves (red lines). C, D. As A, B but in slices cultured from C57 tauKO mice. Scale bars = 1 µm. ",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "E. Quantification of last 10 seconds of fluorescence recovery (90-100 seconds) in B and D. Error bars represent SEM and statistical significance was calculated according to the Mann-Whitney U test. N = 13, 11 and 12 spines for wt baseline, cLTD and recovery and 9, 7 and 5 spines for tauKO baseline, cLTD and recovery groups, respectively.",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "F. Spine/dendrite ratios showing enrichment of EGFP-GSK3α in wild-type or tauKO slices in 'baseline', 'cLTD' or 'recovery' conditions. Error bars represent SEM and statistical significance was calculated according to the Mann-Whitney U test.",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "B. Representative traces for C-F, showing evoked AMPAR- and NMDAR-mediated EPSCs (collected at −60 mV and +40 mV, respectively) in paired uninfected (black traces) and EGFP-GSK3α-expressing neurons (green traces) in C57 wt or tauKO slices.",
    "ncbi_link": "EGFP: 
GSK3α: 606496
tau: 17762"
  },
  {
    "caption": "C-F. Scatter plots showing individual recordings of pairs of uninfected and infected neurons at −60 mV (AMPAR-mediated EPSCs) in C57 wt (C) or tauKO slices (D), or at +40 mV (NMDAR-mediated EPSCs) in wt (E) or tauKO slices (F). Red circles represent the averages of all pairs in a given plot, and n denotes the number of cell pairs. In all cases, error bars represent SEM and statistical significance was calculated according to the Mann-Whitney U test.",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "C) Nuclear and cytoplasmic full-length RNA-Seq data from AC16 cells kept at 37°C or exposed to 18°C for 24h for REV-ERBα and CRY2. Data for each track have been normalized to show counts per million aligned counts (CPM) for each nucleotide. Number of 3' end RNA-seq sample replicates: 37°C (C: 6, N: 7), 18°C 5h (4), 10h (4), 24h (6), 18°C 24h then 37°C 2h (4), 5h (2), 10h (2), 24h (2). Number of cytoplasmic (C) and nuclear (N) samples are the same for each condition except 37°C",
    "ncbi_link": "CRY2: 1408
REV-ERBα: 9975"
  },
  {
    "caption": "Representative maximum intensity z-stack-projected images of DAPI-stained (blue) AC16 exposed to 18°C and returned to 37°C for the time periods indicated, probed by RNA-FISH for REV-ERBα",
    "ncbi_link": "REV-ERBα: 9975"
  },
  {
    "caption": "Representative maximum intensity z-stack-projected images of DAPI-stained (blue) AC16 exposed to 18°C and returned to 37°C for the time periods indicated, probed by RNA-FISH for CRY2 (B)",
    "ncbi_link": "CRY2: 1408"
  },
  {
    "caption": "Representative maximum intensity z-stack-projected images of DAPI-stained (blue) AC16 exposed to 18°C and returned to 37°C for the time periods indicated, probed by RNA-FISH for TP53 (C)",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Representative maximum intensity z-stack-projected images of DAPI-stained (blue) U2OS cells (D), exposed to 18°C and returned to 37°C for the time periods indicated, probed by RNA-FISH for REV-ERBα",
    "ncbi_link": "REV-ERBα: 9975"
  },
  {
    "caption": "Mean REV-ERBα per AC16 cell nuclear and cytoplasmic area across all images for each condition from quantification of the RNA-FISH data. AC16 cells (REV-ERBα): 37°C (65), 18°C 5h (30), 18°C 5h then 37°C 2h (21), 18°C 24h (63), 18°C 24h then 37°C 2h (64)",
    "ncbi_link": "REV-ERBα: 9975"
  },
  {
    "caption": "Mean CRY2 (F) per AC16 cell nuclear and cytoplasmic area across all images for each condition from quantification of the RNA-FISH data. ; AC16 cells (CRY2): 37°C (43), 18°C 24h (42), 18°C 24h then 37°C 2h (42)",
    "ncbi_link": "CRY2: 1408"
  },
  {
    "caption": "Mean TP53 (G) transcripts per AC16 cell nuclear and cytoplasmic area across all images for each condition from quantification of the RNA-FISH data. AC16 cells (TP53): 37°C (47), 18°C 24h (45), 18°C 24h then 37°C 2h (48)",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Mean REV-ERBα per U2OS (H) cell nuclear and cytoplasmic area across all images for each condition from quantification of the RNA-FISH data. U2OS cells (REV-ERBα): 37°C (61), 18°C 5h (61), 18°C 5h then 37°C 2h (69), 18°C 24h (53), 18°C 24h then 37°C 2h (65)",
    "ncbi_link": "REV-ERBα: 9975"
  },
  {
    "caption": "A,B) Mean baseline-detrended bioluminescence profiles from plate wells containing either PER2::LUC U2OS cells with (WT, left panel) or without REV-ERBα (KO, right panel) recorded at 37°C before and after transfer to 18°C for 24h (A) or 5h (B) (grey region) from biological repeat 1. 6 differently colored profiles represent cells synchronized at 6 distinct phases of the circadian period prior to the start of 18°C exposure (time zero).",
    "ncbi_link": "LUC: 
REV-ERBα: 9975
PER2: 18627"
  },
  {
    "caption": "E) Bar graphs showing the mean amplitude change (left axis) following 18°C exposure for 5h for each group of plate well profiles (grouped according to their distinct phase (a-f) prior to 18°C exposure, 10 wells per group) for both WT and KO cells from biological repeats 1 and 2. Mean changes are plotted to approximately align with the position of the control profile at the point of rewarming within the circadian period that is represented by the PER2:LUC (dashed line) and predicted REV-ERBα expression level (right axis) (grey shaded region (light grey indicates REV-ERBα deletion)).",
    "ncbi_link": "LUC: 
REV-ERBα: 9975
PER2: 18627"
  },
  {
    "caption": "K Quantification of ex vivo BLI of brains and thoracic  regions at the endpoint of the experiment. Values are shown in box-and-whisker plots where every dot represents a different animal and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n=9 shControl mice  and n=10 shAHR#1  mice). P value was calculated using two-tailed t-test.",
    "ncbi_link": "AHR: 11622"
  },
  {
    "caption": "F The recombinant UBE2S ER/ER variant increases Cyclin B degradation in G1 extracts compared to UBE2S wild-type (WT), monitored by immunoblot. G1 extracts were prepared from HeLa S3 cells treated with either control firefly luciferase siRNA (siFF) or two UBE2S siRNAs (siUBE2S).",
    "ncbi_link": "UBE2S: 27338"
  },
  {
    "caption": "Kaplan-Meier survival graph indicates prolonged life span of Wwox knockout mice injected with AAV9-hSynI-mWwox [total n=18, spontaneously dead n=6, mice taken out for electrophysiology/electron microscopy/analysis, are shown in yellow, n=12] compared to mice injected with AAV9-hSynI-GFP (n=6) or the non-injected (n=8 (P <0.0001, Log-rank Mantel-Cox test).",
    "ncbi_link": "GFP: 
hSynI: 6853
Wwox: 80707
mWwox: 80707"
  },
  {
    "caption": "Immunofluorescence images showing the expression of WWOX (red) in brain tissue (cortex) at P17 from WT and Wwox null mice that were injected with AAV9-hSynI-mWwox (2x1010). Neurons are labelled with anti-NeuN antibody (green). The square white box shows the magnified area. White arrows show the transgene expression in NeuN positive cells. Graph showing the percentage of NeuN and WWOX double positive cells in different parts of the brain (Cortex, Hippocampus and Cerebellum) from KO mice injected with AAV-mWwox at P17. NeuN and WWOX double positive cells were calculated from 3 identical sagittal sections of the AAV-mWwox injected mice (n=3) brains.",
    "ncbi_link": "hSynI: 6853
Wwox: 80707
mWwox: 80707"
  },
  {
    "caption": "Kaplan-Meier survival graph indicates prolonged life span of Wwox knockout mice injected with AAV9-hWWOX [total n=16, alive n=6, spontaneously dead n=6, 4 mice (shown in yellow) were taken out for analysis) compared to the non-injected (n=8)] (P <0.0001, Log-rank Mantel-Cox test).",
    "ncbi_link": "Wwox: 80707
hWWOX: 51741"
  },
  {
    "caption": "D-F. Immunofluorescence images showing the expression of WWOX (magenta) in cortex (D), Hippocampus (E) and Cerebellum (F) at P19 from WT and Wwox null mice that were injected with AAV-hWWOX (2x1010) or Wwox null alone. Neurons are labelled with anti-NeuN antibody (green). The square white box shows the magnified area.   Graph represents the percentage of neurons showing the transgene (NeuN and WWOX positive) expression at different parts (cortex, hippocampus and cerebellum) of the KO brain at P19 after AAV injection. NeuN and WWOX double positive cells were calculated from 3 identical sagittal sections of the AAV-hWWOX injected mice (n=3) brains.   ",
    "ncbi_link": "Wwox: 80707
hWWOX: 51741"
  },
  {
    "caption": "Representative traces of cell-attached recordings performed in WT (blue), KO (red) and KO injected with either with AAV9-hSynI-mWwox (KO+A-mW shown in purple) or AAV9-hSynI-hWWOX (KO+A-hW shown in green) pups at P18-21 days. Traces represent spontaneous neocortical activity (action potentials shown). The panels represent 12 s recording with an inset presenting a zoom-in of an 0.5 s interval.   The graph shows the recordings (P18-21) averages over 30 neurons from WT (n=3), 30 neurons from KO+A-mWwox (n=3), 30 neurons from KO+A-hWWOX (n=3), and 45 neurons from KO (n=3).   ",
    "ncbi_link": "hSynI: 6853
hWWOX: 51741
mWwox: 80707"
  },
  {
    "caption": "Immunofluorescence staining with anti-GFAP (shown in green) and anti-Iba1 (shown in magenta) antibodies showing the expression of astrocytes and microglia at P19 from WT, KO and KO+A-hWWOX. The square white box shows the magnified area from CA3 regions of hippocampus from all the genotypes. F, G. Graphs represents the quantification of GFAP (F) and Iba1 (G) positive cells from the images shown in E. The number of GFAP or Iba1 cells were counted from 3 identical sagittal sections from CA3 region per group (n=3 per each genotype). ",
    "ncbi_link": "hWWOX: 51741"
  },
  {
    "caption": "H. Immunocytochemical images showing astrocytes (anti-GFAP) and microglia (anti-Iba1) in CA3 region of hippocampus from WT (n=3) and rescued (KO+AAV-hWWOX) (n=3) mice at 9 months. Magnified area is shown with square box. I, J. Graphs represents the quantification of GFAP (I) and Iba1 (J) positive cells from the images shown in H. The number of GFAP or Iba1 cells were counted from 3 identical sagittal sections (paraffin embedded) from CA3 region per group (n=3 per each genotype). ",
    "ncbi_link": "hWWOX: 51741"
  },
  {
    "caption": "Sagittal section of the brain (P17) tissues immunostained for CC1 (green) and PDGFRα (magenta). Images showing increased number of matured oligodendrocytes in corpus callosum of the Wwox null after treatment with AAV-mWwox compared to Wwox null injected with AAV-GFP virus.   Graph represents the quantification of CC1 and PDGFRα positive cells in corpus callosum (area 0.5 mm2) of WT (n=3), KO (n=3) and KO+A-mWwox (n=3) counted from three similar brain sagittal sections per mouse in each genotype.   ",
    "ncbi_link": "GFP: 
Wwox: 80707
mWwox: 80707"
  },
  {
    "caption": "Electron micrograph (EM) images from mid sagittal section of corpus callosum showing increased number of myelinated axons in AAV9-hSynI-mWwox-injected mice compared to Wwox-null mice (KO) at P17.   Graph showing average number of myelinated axons in corpus callosum from WT (n=3), KO (n=3) or KO mice injected with AAV9-hSynI-mWwox (n=3) per field of view (FOV).   g-ratio analysis showing reduced myelin thickness of axons in corpus callosum KO (n=3) compared to the KO+AAV-Wwox (n=3). Axon diameter and myelin thickness was calculated from the electron micrograph images of corpus callosum (total no of axons n=350 per each group).   ",
    "ncbi_link": "hSynI: 6853
Wwox: 80707
mWwox: 80707"
  },
  {
    "caption": "EM images showing increased number of myelinated axons in optic nerve in AAV9-hSynI-mWwox injected mice compared to KO mice at P17.   Graph showing the average number of myelinated axons (counted per FOV) in optic nerve from WT (n=3), KO (n=3) and KO+AAV-mWwox(n=3).   g-ratio's of myelinated axons from optic nerves showing improved myelin thickness (less g-ratio) after WWOX restoration (KO+AAV-mWwox) compared to KO alone (n=3 per genotype, total no of axons n=200 per each group).   ",
    "ncbi_link": "hSynI: 6853
mWwox: 80707"
  },
  {
    "caption": "Representative images of open field test showing tracking pattern (open arena) of WT (females, n=7, males n=6) and AAV-mWwox-injected KO mice (females n=7, males n=5) at 8-10 weeks. Dot plot graphs represent the velocity (B), total distance travelled (C)",
    "ncbi_link": "mWwox: 80707"
  },
  {
    "caption": "(I) AREG+NK cells from control or RUNX3 knockout groups were detected after IL-12+IL-15+IL-18 stimulation in MACS NK medium at 37°C in 5% CO2 for 16 hrs (n= two-tailed paired t-test. All data were generated using blood from healthy HIV-1-negative donors.",
    "ncbi_link": "RUNX3: 864"
  },
  {
    "caption": "(I, J) NSG (n=15) or human IL-15 transgenic NSG (NSG-huIL-15) mice (n=15) were reconstituted with human CD34+ hematopoietic stem cells for 6 weeks. Blood, spleen, and liver were harvested for detection of CD56 (I) or IFN-γ production after 16 hrs stimulation with IL-12, IL-15, and IL-18 (J).",
    "ncbi_link": "IL-15: 3600"
  },
  {
    "caption": "A Pup survival analysis between P0-P10, by sex. Each dot represents the absolute percent of remaining animals per group (Jag1CTRL n=211, male Jag1Ndr/Ndr n=26, female Jag1Ndr/Ndr n= 20, log-rank test, ****P<0.0001).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "G-I µCT of P30 skulls. (G) Color map depicting wall thickness. Scale bar 3.5 mm. (H) Skull full thickness volume (n=5-6 per group, two-way ANOVA. Interaction P= 0.7595; Sex P= 0.1164, Genotype **P= 0.0012. Šídák's multiple comparisons test: Male Jag1+/+ vs Jag1Ndr/Ndr *P= 0.0227; : Female Jag1+/+ vs Jag1Ndr/Ndr *P= 0.034), (I) Compact bone total volume (n=5-6 per group, two-way ANOVA. Interaction P= 0.8631; Sex P= 0.0901, Genotype **P= 0.0014. Šídák's multiple comparisons test: Male Jag1+/+ vs Jag1Ndr/Ndr *P= 0.0305; Female Jag1+/+ vs Jag1Ndr/Ndr *P= 0.0307).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "L Adult brain Evans blue assay (Jag1CTRL n=7, Jag1Ndr/Ndr n=8, unpaired t test, ns, P=0.3807).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "M Hemorrhagic P3 Jag1Ndr/Ndr brain (n= 2/83 Jag1Ndr/Ndr mice, sex n.d.).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "N Hemorrhagic P15 Jag1Ndr/Ndr retina. Scale bar 20 µm. Sex n.d.",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "O Red blood cells outside P10 Jag1Ndr/Ndr retinal arteriole. Scale bar 10 µm.",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(B) Arteriovenous crossings number per retina (n=6 per group, two-way ANOVA with Tukey's multiple comparisons test. Interaction P = 0.7074, Sex P =>0.9999, Genotype ****P= <0.0001, Tukey's multiple comparisons test: Male:Jag1+/+ vs. Male:Jag1Ndr/Ndr *P= 0.0201; Female:Jag1+/+ vs. Female:Jag1Ndr/Ndr **P= 0.0061).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "C-D (C) Number of major arterioles (n=6 per group, two-way ANOVA with Tukey's multiple comparisons test. Interaction P = 0.4353, Sex P =0.1995, Genotype ****P= <0.0001, Tukey's multiple comparisons test: Male:Jag1+/+ vs. Male:Jag1Ndr/Ndr *P= 0.0146; Female:Jag1+/+ vs. Female:Jag1Ndr/Ndr **P= 0.0011) and (D) venules (n=6 per group, two-way ANOVA with Tukey's multiple comparisons test. Interaction P = 0.044, Sex P =0.044, Genotype ****P= <0.0001, Tukey's multiple comparisons test: Male:Jag1Ndr/Ndr vs. Female:Jag1Ndr/Ndr *P=0.0302; Female:Jag1+/+ vs. Female:Jag1Ndr/Ndr ***P= 0.0002).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "E-F (E) Arterial tortuosity at P30 and 1 year, irrespective of sex (n=6 per group, two-way ANOVA, not significant). (F) Arterial tortuosity in male and female mice, irrespective of age (n=5-7, two-way ANOVA, not significant). G-H (G) Venous tortuosity at P30 and 1 year, irrespective of sex (n=6-8 per group, two-way ANOVA with Tukey's multiple comparisons test. Interaction P = 0.1166, Age P = 0.0787, Genotype **P=0.0013. Tukey's multiple comparisons test: P30:Jag1+/+ vs. P30:Jag1Ndr/Ndr **P=0.004; P30:Jag1Ndr/Ndr vs. 1 year:Jag1Ndr/Ndr P=0.0802; 1 year:Jag1+/+ vs. 1 year:Jag1Ndr/Ndr P= 0.5066). (H) Venous tortuosity in male and female mice, irrespective of age (n=5-7, two-way ANOVA with Tukey's multiple comparisons test. Interaction *P = 0.0223, Sex **P = 0.007, Genotype ***P= <0.0001. Tukey's multiple comparisons test: Male:Jag1+/+ vs. Male:Jag1Ndr/Ndr P= 0.3247, Male:Jag1Ndr/Ndr vs. Female:Jag1Ndr/Ndr **P= 0.0031, Female:Jag1+/+ vs. Female:Jag1Ndr/Ndr ****P= 0.0001).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(K) Visualization of MCA with alpha smooth muscle cell actin (αSMA) showed stereotype vasculature in 6 of 6 Jag1+/+ animals, but 2 of 6 Jag1Ndr/Ndr animals showed highly divergent MCA architecture (blue arrows).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(G) Number of α SMA negative gaps per retina and mouse by age (Two-way ANOVA with Sidak's multiple comparisons test. Dots represent biological replicates/individual retinas/mice. Two-way ANOVA not significant. Šídák's multiple comparisons test: 1 year Jag1+/+ vs 1 year Jag1Ndr/Ndr *P= 0.0189).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(N) Blood pressure (BP) before treatment in male and female Jag1CTRL and Jag1Ndr/Ndr mice. Each dot represents one animal/one biological replicate. (Two-way ANOVA Interaction P=0.9407, Sex P=0.4957, Genotype *P= 0.0207. Šídák's multiple comparisons test not significant).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(O) Blood pressure increase in Jag1CTRL and Jag1Ndr/Ndr mice treated with vehicle or AngII for two weeks (Jag1+/+ ctrl n=4, Jag1+/+ AngII n=4, Jag1Ndr/Ndr ctrl n=5, Jag1Ndr/Ndr AngII n=5, two-way ANOVA, with Sidak's multiple comparisons).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(P) Detection of Evans blue leakage in brain in Jag1CTRL and Jag1Ndr/Ndr mice with or without AngII treatment. (Jag1+/+ ctrl n=4, Jag1+/+ AngII n=4, Jag1Ndr/Ndr ctrl n=5, Jag1Ndr/Ndr AngII n=5, two-way ANOVA, with Sidak's multiple comparison. Interaction P=0.9687, Treatment **P=0.007, Genotype P=0.5058).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(Q) One Jag1Ndr/Ndr mouse (male) displayed a macroscopic EB leakage, upon AngII treatment.",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "® Retinal arteriolar αSMA coverage in vehicle or AngII-treated mice. Green arrowheads denote stenosis, blue arrowheads label αSMA-negative gap. (S) αSMA-negative gaps in arterioles per retina (Jag1+/+ ctrl n=4, Jag1+/+ AngII n=4, Jag1Ndr/Ndr ctrl n=3-5, Jag1Ndr/Ndr AngII n=5, two-way ANOVA, with Sidak's multiple comparison. Interaction P = 0.1054, treatment P=0.0815; Genotype P=0.0747. Ší'ák's multiple comparisons test: AngII treated Jag1+/+ vs AngII treated Jag1Ndr/Ndr *P= 0.0315).).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "N-P (N) P10 and (O) P40 neurofilament (NF) and CD31 staining. Scale bar 50 µm. (P) % area positive for NF in P10 and P40 mice (n=6 per group, two-way ANOVA: Interaction ***P= 0.0001; Age *P=0.0428; Genotype ***P=0.0004. Sidak's multiple comparisons test: P10 Jag1+/+ vs P10 Jag1Ndr/Ndr P= 0.9246; P40 Jag1+/+ vs P40 Jag1Ndr/Ndr ****P= <0.0001).",
    "ncbi_link": "Jag1: 16449"
  },
  {
    "caption": "(A) siRNA-treated BMDMs were infected for 16 hours with S. Typhimurium (orgA-) and LDH and IL-1β release were measured.",
    "ncbi_link": "orgA: "
  },
  {
    "caption": "(B) Cell death (LDH) and IL-1β release evaluation in WT, Irgm2-/-, GBPChr3-/- and Casp11-/- BMDMs infected for 16 hours with different Gram-negative bacteria (MOI 25).",
    "ncbi_link": "Casp11: 12363
GBP: 229900///229898///55932///14469
Irgm2: 54396"
  },
  {
    "caption": "(C) Western blot examination of processed caspase-1 (p20) and gasdermin-D (p30) in supernatants and pro-caspase-1 (p45), pro-gasdermin-D (p55) and GAPDH in cell lysates of WT and Irgm2-/- BMDMs infected for 16 h with different Gram-negative bacterial strains.",
    "ncbi_link": "Irgm2: 54396"
  },
  {
    "caption": "(D) IL-1β and cell death (% LDH) evaluation in immortalized WT, Irgm2-/-, Casp11-/- and Casp11-/-Irgm2-/- (referred as sgIrgm2) BMDMs after 16 hours of E. coli, S. Typhimurium orgA- and OMV treatment.",
    "ncbi_link": "orgA: 
Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(E) Cell death (% LDH) evaluation in IFNγ-primed WT, Irgm2-/- and Casp11-/- BMDMs 4 hours after electroporation or not with 1µg of E. coli LPS.",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(F-H) Survival of WT, Casp11-/- and Irgm2-/- mice primed with 100µg poly(I:C) for 6 hours and injected (i.p.) with 5mg/k-1 LPS or 5 and 25 µg of OMVs (n=6 animals per condition).",
    "ncbi_link": "Casp11: 12363
Irgm2: 54396"
  },
  {
    "caption": "(A) Measure of LDH and IL-1β release in WT, GBPChr3-/- and Casp11-/- BMDMs were Irgm2 was knocked down 16 hours after exposure to 2,5 µg/2.105 cells of OMVs. Si Scramble (siScr.) refers to RNAi pools with non-targeting sequences.",
    "ncbi_link": "Casp11: 12363
GBP: 229900///229898///55932///14469
Irgm2: 54396"
  },
  {
    "caption": "(B) Cell death (LDH) and IL-1β release evaluation in Irgm2-silenced WT and GBPChr3-/- BMDMs infected for 16 hours with either S.Tm orgA- or F. novicida (MOI 25). Si Scramble (siScr.) refers to RNAi pools with non-targeting sequences.",
    "ncbi_link": "orgA: 
GBP: 229900///229898///55932///14469
Irgm2: 54396"
  },
  {
    "caption": "(C) Florescence microscopy and associated quantifications of GBP-2 (green) recruitments to intracellular S. Tm orgA--mCherry (MOI 10, red) in IFNγ-primed WT and Irgm2-/-BMDMs. Nucleus was stained with Hoechst (blue). Confocal images shown are from one experiment and are representative of n=3 independent experiments; scale bars 5 µm. For quantifications, the percentage of GBP-associated bacteria was quantified and 'n=' refers to the number of intracellular bacteria counted in each experiment; quantifications from n=3 independent experiments were then plotted and expressed as mean ± SEM.",
    "ncbi_link": "orgA: 
mCherry: 
Irgm2: 54396"
  },
  {
    "caption": "(D) Confocal fluorescence microscopy images and associated quantifications of caspase-11-C254G-GFP (green) recruitment to S.Tm-mCherry (orgA-, red) in IFNγ-primed iWT, iIrgm2-/-, iGBPChr3-/- and iGBPChr3-/-/sgIrgm2 BMDMs after 8 hours of infection. Nucleus (blue) was stained with Hoescht; scale bar 5µm. For quantifications, the percentage of bacteria positive for caspase-11-C254G-GFP was determined by combining the bacterial counts from n=3 independent experiments and expressed as mean ± SEM. ***p ≤ 0.001 for the indicated comparisons using t-test with bonferroni correction.",
    "ncbi_link": "mCherry: 
orgA: 
GBP: 229898///229900///55932///14469
GBP: 229900///229898///55932///14469
Irgm2: 54396"
  },
  {
    "caption": "(B) Green Florescent Protein (GFP)-Trap assay of the presence of Gate16 in Irgm2-GFP-enriched fraction from the lysates of IFNγ-primed iIrgm2-/- BMDMs complemented with lentiviral constructs coding for a fusion of Irgm2 withGFP (Irgm2-GFP) or GFP alone. Arrows show the presence or not of Gate16, Irgm2-GFP and GAPDH in the Irgm2-GFP-enriched fractions, flow-through and total cell lysates. * means non-specific band",
    "ncbi_link": "GFP: 
Irgm2: 54396"
  },
  {
    "caption": "(D) LDH and IL-1β release from WT, Irgm2-/- and Casp11-/- BMDMs silenced for Gate16 and treated for 16 hours with 2,5µg/2.105 cells of OMVs. Si Scramble (siScr.) refers to RNAi pools with non-targeting sequences.",
    "ncbi_link": "Casp11: 12363
Gate16: 93739
Irgm2: 54396"
  },
  {
    "caption": "(E) Western blot examination of caspase-11 and processed caspase-1 (p20)and gasdermin-D (p30) in supernatants and pro-caspase-1 (p45), pro-gasdermin-D (p55), pro-caspase-11, Gate16 and GAPDH in cell lysates of Gate16-silenced WT, Irgm2-/- and GBPChr3-/- BMDMs exposed to 2,5.105µg/2.105 cells of OMVs for 16 hours. Si Scramble (siScr.) refers to RNAi pools with non-targeting sequences.",
    "ncbi_link": "Gate16: 93739
GBP: 55932///14469///229900///229898
Irgm2: 54396"
  },
  {
    "caption": "(F) Representative confocal fluorescence microscopy images and associated quantifications of caspase-11-C254G-GFP (green) recruitment to S.Tm-mCherry (orgA-, red, MOI 10) in IFNγ-primed iWT BMDMs silenced for Gate16 after 4 and 8 hours of infection. Nucleus (blue) was stained with Hoechst; scale bar 5µm. For quantifications, the percentage of bacteria positive for caspase-11-C254G-GFP was determined by combining the bacterial counts from n=3 independent experiments and expressed as mean ± SEM. **p ≤ 0.01, ***p ≤ 0.001 for the indicated comparisons using t-test with bonferroni correction. Si Scramble (siScr.) refers to RNAi pools with non-targeting sequences.",
    "ncbi_link": "mCherry: 
orgA: 
Gate16: 93739"
  },
  {
    "caption": "(A) LDH and IL-1B release from siRNA-treated primary human Monocyte-Derived Macrophages (hMDMs) infected with S. Typhimurium orgA- (MOI25) for 16 hours. When specified, the caspase-4/5 inhibitor Z-LEVD (25µM) or the NLRP3 inhibitor MCC950 (10µM) were added to the experiments.",
    "ncbi_link": "orgA: "
  },
  {
    "caption": "(C, D) LDH and IL-1B release from siRNA-treated WT or GBP1/2/5-/- U937 Monocytic cell line, primed with IFNγ (10UI/mL) and PAM3CSK4 (100ng/mL) and then infected with (C) with S. Typhimurium orgA- (MOI25) for 10 hours or (D) electroporated with 1µg of E. coli LPS for 4 hours. Φ indicates that no LPS electroporation was performed.",
    "ncbi_link": "orgA: 
GBP1: 2633"
  },
  {
    "caption": "Wild-type, apg12-1 mutant and Δapg12 cells were cultured in nitrogen-starvation medium containing 1 mM PMSF. After incubation for 6 h, cells were observed under a phase-contrast microscope. Arrows indicate autophagic bodies.",
    "ncbi_link": "apg12: 852518
apg12-1: 852518"
  },
  {
    "caption": "c, Wild-type (squares) and Δapg12 (circles) were cultured in nitrogen-starvation medium and their viability was determined by phloxine B staining.",
    "ncbi_link": "apg12: 852518"
  },
  {
    "caption": "d, Quantification of autophagic activity of wild-type and Δapg12 cells by alkaline phosphatase (ALP) assay before (black bars) and after (white bars) nitrogen starvation for 4 h. Error bars indicate s.d. of three independent experiments.",
    "ncbi_link": "apg12: 852518"
  },
  {
    "caption": "a, b, Lysates from Δapg12 cells carrying only vector or 3 × HA-APG12 (a), and Δapg5, apg7-1, apg10-1 and Δapg1 cells carrying 3 × HA-Apg12 plasmid (b) were immunoblotted using anti-HA antibody. The positions of 3 × HA-Apg12 and the larger product (asterisks) are indicated.",
    "ncbi_link": "apg1: 852695
apg10-1: 850684
APG12: 852518
apg12: 852518
apg5: 855954
apg7-1: 856576"
  },
  {
    "caption": "c, Immunoblot analysis of wild-type and Δapg12 cells harbouring HA-APG5 plasmid.",
    "ncbi_link": "apg12: 852518
APG5: 855954"
  },
  {
    "caption": "d, Δapg5 Δapg12 cells were co-transformed with Myc-APG12 and HA-APG5. Their lysates were immunoprecipitated with anti-Myc or anti-HA antibodies and detected by immunoblotting using anti-Myc antibody. The position of the crossreacting IgG heavy chain is indicated",
    "ncbi_link": "APG12: 852518
APG5: 855954"
  },
  {
    "caption": "b, Δapg12 cells were transformed with the mutant plasmids and their lysates were immunoblotted with anti-HA antibody.",
    "ncbi_link": "apg12: 852518"
  },
  {
    "caption": "Δapg5 cells were transformed with vector alone, wild-type APG5 or APG5K149R, and then immunoblotted with anti-HA (b)",
    "ncbi_link": "APG5: 855954"
  },
  {
    "caption": "Δapg5 cells were transformed with vector alone, wild-type APG5 or APG5K149R, and then immunoblotted anti-API (d).",
    "ncbi_link": "apg5: 855954"
  },
  {
    "caption": "c, In vitro conjugation of Apg5 and Apg12. A cell lysate of Δapg12 carrying HA-APG5 (lane 1) was incubated with an equal amount of lysate from Δapg5 carrying HA-APG12 (2 µ plasmid) (lane 2) at 30 °C with (lane 4-6) or without (lane 7) 5 mM ATP. Samples were mixed with SDS-sample buffer at the times indicated.",
    "ncbi_link": "apg12: 852518
APG5: 855954
apg5: 855954"
  },
  {
    "caption": "Spheroplasts were generated from cells expressing either HA-Apg12 or HA-Apg5. Their lysates were mixed and layered on top of a 10-step (18-54 % w/w) sucrose gradient, and centrifuged at 174,000g for 2.5 h (ref. 29). Fifteen fractions were collected and the positions of free Apg5, free Apg12 and Apg5/Apg12 conjugate were examined by western blotting. The peak fractions of alcohol dehydrogenase (ADH)(cytosol), ALP (vacuole), Kex2 (Golgi) and Sec12 (endoplasmic reticulum) are indicated by arrows.",
    "ncbi_link": "Apg12: 852518
Apg5: 855954"
  },
  {
    "caption": "F. Ubc1-EA was genomically integrated into various yeast strains. Exponentially growing cells of the indicated genotype were spotted onto YPD plates in serial 10‑fold dilutions. Where noted cells were incubated at elevated temperature (37 °C) or in presence of hydroxyurea (HU) to induce DNA replication stress.",
    "ncbi_link": "Ubc1: 851757"
  },
  {
    "caption": "(a,b) Immunoblot analysis of LAMP-2A in total lysates (a) and quantitative PCR analysis of Lamp2a mRNA (b) of naive CD4+ T cells and TH1 and TH2 cells following activation with anti-CD3 and anti-CD28. β-actin (a) serves as a loading control throughout; mRNA results (b) are presented relative to those of resting cells.",
    "ncbi_link": "Lamp2a: 3920"
  },
  {
    "caption": "(g) Immunoblot analysis of LAMP-2A in resting TH1 cells and TH1 cells activated in the presence (NAc) or absence (Veh) of N-acetylcysteine. (h) Quantitative PCR analysis of Lamp2a mRNA in cells as in g (results presented as in b). *P = 0.007 (t test).",
    "ncbi_link": "Lamp2a: 3920"
  },
  {
    "caption": "(k) Immunoblot analysis of LAMP-2A in total lysates of resting TH1 cells (−) and TH1 cells activated for 24 h as in a,b (+), transfected with a control nontargeting siRNA (with a scrambled sequence (Scr)) or siRNA specific for mRNA encoding Duox1 (either of two siRNAs: Dx(1) and Dx(2)) or RISP (Uq(1)).",
    "ncbi_link": "Duox1: 53905
RISP: 7386"
  },
  {
    "caption": "(m) Chromatin-immunoprecipitation analysis of the recruitment of NFAT1 to the promoter of Lamp2 or Adad1 (negative control) (left) or to Il2 (positive control) (right) in resting and activated TH1 cells; results are presented relative to input chromatin precipitated with anti-NFAT1.",
    "ncbi_link": "Adad1: 132612
Il2: 3558
Lamp2: 3920"
  },
  {
    "caption": "(a) Flow cytometry of T cells transduced with lentivirus expressing GFP and nontargeting control shRNA (Scr) or Lamp2a mRNA-specific shRNA (shL2A) (left), and immunoblot analysis of LAMP-2A in sorted GFP+ T cells (right). Numbers above bracketed lines (left) indicate percent GFP+ cells.",
    "ncbi_link": "Lamp2a: 3920"
  },
  {
    "caption": "(d) Immunoblot analysis of lysates of TH1 cells transfected with GFP-Itch or GFP-mu-Itch (top) or with Myc-RCAN1 or Myc-mu-RCAN1 (bottom) and cotransfected with a GFP expression plasmid (to assess transfection efficiency), then activated for 24 h as in a.",
    "ncbi_link": "Itch: 83737
RCAN1: 1827"
  },
  {
    "caption": "(a) Immunoblot analysis of LAMP-2A in CD4+ T cells (left) and liver, kidneys, thymus and lungs (right) of L2A-cKO mice (KO) and their control littermates (Ctrl).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(b) Quantitative PCR analysis of Lamp2a, Lamp2b and Lamp2c mRNA in T cells from L2A-cKO mice (right); results are presented relative to those of their control littermates (left), set as 1.",
    "ncbi_link": "L2A: 16784
Lamp2a: 16784
Lamp2b: 16784
Lamp2c: 16784"
  },
  {
    "caption": "(c) Immunoblot analysis of the autophagy related protein LC3 in its cytosolic form (LC3-I) and its autophagosome membrane-associated form (LC3-II) in total lysates of CD4+ T cells obtained from L2A-cKO mice or their control littermates and then left unstimulated (Rest) or activated for 24 h with anti-CD3 and anti-CD218 (Act), cultured for the final 4 h in the presence (+) or absence (−) of NH4Cl and leupeptin (NH4Cl+Leup).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(d) Spleens from an L2A-cKO mouse and its control littermate (left), and flow cytometry of peripheral T cells from such mice (right). Numbers in quadrants (right) indicate percent CD4−CD8+ T cells (top left) or CD4+CD8− T cells (bottom right).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(e,f) Proliferation (e) and IL-2 production (f) by CD4+ T cells isolated from the spleen of L2A-cKO mice and their control littermates and stimulated ex vivo for 48 h with anti-CD3 and anti-CD28 (assessed as in Fig. 2c (e) or Fig. 2b (f)). *P = 0.0062 (e) or 0.006 (f) (t-test).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(g) Immunoblot analysis of LAMP-2A, Itch and RCAN1 in total lysates of CD4+ T cells obtained from L2A-cKO mice (n = 3 (KO1, KO2 and KO3)) and their control littermates (n = 3) and activated for 24 h as in e,f. *, nonspecific band.",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(h) Quantitative PCR analysis of Rcan1 and Itch mRNA in CD4+ T cells isolated from L2A-cKO mice and their control littermates and activated for 24 h as in e,f; results are presented relative to those of resting cells.",
    "ncbi_link": "Itch: 16396
L2A: 16784
Rcan1: 54720"
  },
  {
    "caption": "(i,j) Recall responses to OVA(323-339) in draining lymph nodes isolated from L2A-cKO mice and their control littermates after immunization with OVA(323-339), assessed as proliferation (i) and IL-2 production (j) (as in e,f). *P = 0.0054 (i) or 0.0052 (j) (t-test).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(k,l) Recall responses to L. monocytogenes in CD4+ T cells isolated from L2A-cKO mice and their control littermates (n = 6 per group) previously uninfected (UI) or previously infected with L. monocytogenes (Inf), assessed as IFN-γ production (k) and proliferation (l) (as in e,f). *P = 0.032 (k) or 0.02 (l) (t-test).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(m) L. monocytogenes in spleen and liver of L2A-cKO mice and their control littermates (n = 3 per genotype) immunized with L. monocytogenes and then reinfected with a high dose of L. monocytogenes. CFU, colony-forming units. *P = 0.008 and **P = 0.001 (t-test).",
    "ncbi_link": "L2A: 16784"
  },
  {
    "caption": "(g-i) Immunoblot analysis of LAMP-2A (g) and analysis of the proliferation (h) and IL-2 production (i) of TH1 cells obtained from 4- or 22-month-old mice and transduced with retrovirus expressing GFP alone (RV-GFP) or human LAMP-2A and GFP (RV-LAMP2A), sorted by GFP expression, cultured for 2 weeks and then stimulated for 24-48 h as in a (assessed as in Fig. 2c (h) or Fig. 2b (i)). *P 0.05 (analysis of variance with Tukey's post-test).",
    "ncbi_link": "LAMP2A: 3920"
  },
  {
    "caption": "(k) Real-time PCR analysis of LAMP2A mRNA in naive and memory CD4+ T cells obtained from young human donors (26 ± 2 years of age; n = 3) or old human donors (72 ± 6 years of age; n = 6) and activated for 24 h as in a; results were calculated by the change-in-cycle-threshold method (2−ΔCt) relative to those of the gene encoding β-actin. *P = 0.047 and **P = 0.0033 (Mann-Whitney).",
    "ncbi_link": "β-actin: 
LAMP2A: 3920"
  },
  {
    "caption": "B Quantitative analysis of PI-positive cells treated with H2O2 was shown (42.9 ± 3.1% in wild-type group vs. 10.1 ± 4.4% in Cuedc2-/- group, * p = 0.0004, n = 5 wells per group and repeated for three times).",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "A Protein was extracted from the area at risk of left ventricle from wild-type or Cuedc2-/- mice with 30-minute ischemia followed by 30-minute reperfusion and subjected to immunoblot analysis. Representative results from 2 mice are shown, and each experiment was repeated for three times.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "C Luciferase assay of WT or Cuedc2-/- MEFs transiently transfected with an NF-κB-responsive luciferase reporter and then, 1 d later, treated for 6 h with TNF (10 ng/ml; TNF) or for H/R. * p = 0.0032, n = 3 per group, ** p = 0.013, n = 3 per group.",
    "ncbi_link": "luciferase: 
Cuedc2: 67116
NF-κB: 18034///18033"
  },
  {
    "caption": "D Wild-type and Cuedc2-/- mice were treated with a sham or I/R operation in vivo. Three hours after the onset of reperfusion, the mRNA levels of tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and interleukin 23 (IL-23) were tested. * p = 0.0005, ** p = 0.0001, n = 3 per group.",
    "ncbi_link": "Cuedc2: 67116
IL-23: 83430
IL-6: 16193
TNFα: 21926"
  },
  {
    "caption": "A Protein was extracted from the left ventricle of wild-type or Cuedc2-/- adult mice (12 week-old) and subjected to immunoblot analysis (3 mice per group).",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "B Wild-type or Cuedc2-/- mice were subjected to a heart ischemia for 30-minute in vivo, followed by reperfusion for the indicated times. Protein was extracted from the area at risk of left ventricle and subjected to immunoblot analysis.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "D Primary neonatal mousecardiomyocytes stably expressing control or GPX1 shRNA by lentivirus infection were treated with H2O2 (1 mM) for 3 hours. Cell viability was detected by FACS. * p = 0.0001; ** p = 0.0275, n = 3 wells per group. NS, not significant.",
    "ncbi_link": "GPX1: 14775"
  },
  {
    "caption": "E Primary neonatal mousecardiomyocytes were transfected with lentivirus carrying control or GPX1 shRNA, and the efficiency of GPX1 knockdown was tested by immunoblotting.",
    "ncbi_link": "GPX1: 14775"
  },
  {
    "caption": "F Primary neonatal mousecardiomyocytes stably expressing control or GPX1 shRNA by lentivirus infection were subjected to H2O2 (1 mM) for 30 minutes and then stained with 5 μM CellROX® Deep Red Reagent and analyzed by flow cytometry. * p = 0.0056; ** p = 0.0218, n = 3 wells per group, n = 3 wells per group. NS, not significant.",
    "ncbi_link": "GPX1: 14775"
  },
  {
    "caption": "A Lysates from MEF-WT or MEF-Cuedc2-/- cells treated with 20μM cycloheximide (CHX) for the indicated times were subjected to immunoblotting (left). Relative GPX1 levels were quantified by densitometry (right).",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "B MEF-Cuedc2-/- cells were transfected with increasing amounts of FLAG-CUEDC2 (mouse) plasmids (1 μg and 2 μg). At 24 hours after transfection, the cells were treated with the proteasome inhibitor MG-132 (10 μM). Cells were cultured for additional 6 hours and subjected to immunoblotting.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "C HEK293T cells were transfected with the FLAG-GPX1, HA-CUEDC2, and Myc-ubiquitin plasmids as indicated and treated with MG-132 (10 µM) for 6 hours before harvest. Cell lysates were immunoprecipitated (IP) with anti-FLAG (M2). The immunoprecipitates were analyzed by western blot using an anti-GPX1 antibody. Whole-cell lysates (WCL) were analyzed by Western blots with anti-FLAG or anti-HA antibody to determine the protein of Flag-GPX1 and HA-CUEDC2.",
    "ncbi_link": "CUEDC2: 79004
GPX1: 2876
ubiquitin: 7311///6233///7316///7314"
  },
  {
    "caption": "D The heart tissue lysates from wide-type and Cuedc2-/- mice were incubated with IgG or anti-GPX1 antibody, and then captured on protein G-Sepharose beads. The immunoprecipitates were analyzed by immunoblotting with an anti-ubiquitin antibody.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "E HEK293T cells were transfected with the Flag-CUEDC2 or Flag-CUEDC2△CUE (deletion of the CUE domain of CUEDC2), and treated with MG-132 (10 µM) for 6 hours before harvest. Cell lysates were immunoprecipitated (IP) with anti-Flag (M2). The immunoprecipitates were analyzed by western blot using an anti-GPX1 antibody. Whole-cell lysates (WCL) were analyzed by Western blots with anti-Flag or anti-GPX1 antibody to determine the protein of Flag-CUEDC2 and GPX1. v: vector.",
    "ncbi_link": "CUEDC2: 79004"
  },
  {
    "caption": "A HEK293 cells were transfected with increasing amounts of Flag-TRIM33 expression vectors and 48 hours after transfection, cell lysates were subjected to immunoblotting (IB) using antibodies as indicated.",
    "ncbi_link": "TRIM33: 51592"
  },
  {
    "caption": "B HEK293 cells were transfected with increasing amounts of Flag-FBXW7 expression vectors and 48 hours after transfection, cell lysates were subjected to immunoblotting (IB).",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "C HEK293T cells were transfected as indicated, at 18 h after transfection, the cells were treated with the proteasome inhibitor MG132 (20μM) for 6 hours and then harvested. Cell lysates were immunoprecipitated by Flag-antibody (M2 beads) and Ubiquitin-conjugated GPX1 was detected by Western blotting with anti-Myc antibody.",
    "ncbi_link": "Ubiquitin: 7311///6233///7316///7314"
  },
  {
    "caption": "D HEK293 cells were transfected with either control or CUEDC2 siRNA and increasing amounts of Flag-TRIM33 expression vectors, cell lysates were subjected to immunoblotting (IB) using antibodies as indicated.",
    "ncbi_link": "CUEDC2: 79004
TRIM33: 51592"
  },
  {
    "caption": "A CUEDC2 ablation reduced I/R injury, which was induced by 30 minutes of ischemia followed by 24 hours reperfusion. AAR, area at risk; LV, left ventricular area, IRI, area of I/R injury. The ratios of AAR to LV, IRI to AAR and IRI to LV are shown. * p < 0.0001 compared with WT, n = 15 mice per group. (top panel) Representative cross-sectional slices derived from the hearts stained by TTC. Area of I/R injury is indicated in light pink.",
    "ncbi_link": "CUEDC2: 67116"
  },
  {
    "caption": "B Representative images of ventricular myocardium sections from WT and Cuedc2-/- mice exposed to sham operation or I/R injury (2 hours after the onset of reperfusion following 30-min ischemia). Green, TUNEL-positive myocytenuclei; red, Troponin I-stained cardiomyocytes; blue, DAPI-stained nuclei. Scale bar, 50 μm.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "B Animals were injected by rAAV9-CUEDC2 in a different amount of viral genomes (VG). Heart tissues were then analyzed by immunoblotting to detect CUEDC2 transduction. Tubulin protein level was examined for normalization purposes.",
    "ncbi_link": "CUEDC2: 67116"
  },
  {
    "caption": "C The ratios of AAR to LV, IRI to AAR and IRI to LV are shown. n = 10 mice in WT + rAAV-GFP group and Cuedc2-/- + rAAV-GFP group; n = 12 mice in Cuedc2-/- + rAAV-CUEDC2 (1×1010 VG) group and Cuedc2-/- + rAAV-CUEDC2 (1×1011 VG) group. * p = 0.0055, ** p = 0.0146, *** p = 0.0200, **** p = 0.0377.",
    "ncbi_link": "CUEDC2: 67116
Cuedc2: 67116"
  },
  {
    "caption": "D Effect of rAAV9-CUEDC2 treatment on echocardiography indices of left ventricle function recovery post-I/R measured by fractional shortening (FS) and ejection fraction (EF). WT+ rAAV-GFP (n = 10); Cuedc2-/- + rAAV-GFP (n = 10); Cuedc2-/- + rAAV-CUEDC2 (Low dose) (n = 12); Cuedc2-/- + rAAV-CUEDC2 (High dose) (n = 12). ** p < 0.0001.",
    "ncbi_link": "CUEDC2: 67116
Cuedc2: 67116"
  },
  {
    "caption": "D Comparison of heart weight / body weight (HW/BW) in WT and Cuedc2-/- mice. ** p = 0.036, n = 15 in young WT and Cuedc2-/- mice, n = 10 in old WT mice and n = 12 in old Cuedc2-/- mice.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "E Comparison of the left ventricle function in WT and Cuedc2-/- mice by transthoracic echocardiography. *p = 0.0384, **p = 0.0389. n = 15 in young WT and Cuedc2-/- mice, n = 10 in old WT mice and n = 12 in old Cuedc2-/- mice.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "G Left ventricle myocardial fibrosis was tested by Masson staining in WT and Cuedc2-/- mice. The represent results were shown in (G) and the quantitative analysis of myocardial fibrosis was shown in (H). *p = 0.0177, n = 5 in each group.",
    "ncbi_link": "Cuedc2: 67116"
  },
  {
    "caption": "(D) Digitonin permeabilized BMK Bax-/-/Bak-/- cells expressing SMAC-mCherry in the mitochondria intermembrane space (50 μL, 500,000 total cells) were incubated with 25 nM of Bax and 2 nM cBid for the indicated time at 37°C in a 96-well plate. The samples were centrifuged for 10 min and separated into supernatant and pellet fractions. SMAC-mCherry release was calculated as the fraction of total (supernatant + pellet) mCherry fluorescence coming from the supernatant fraction. The data was normalized to the percent SMAC-mCherry release of wt Bax and cBid at 60 min. Each symbol represents the normalized SMAC-mCherry release for one single replicate (n = 3 or more independent replicates). Where applicable the data was fit with the [Agonist] vs. response - Variable slope equation in Graphpad Prism 8.0.1. The dotted lines represent the 95% confidence interval of the fit.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(A) UBQLN4 associates with polyubiquitinated proteasomal substrates. Flag-tagged UBQLN4 protein was affinity-purified from extracts of HeLa cells that were treated with (+) or without (-) 20 μM MG-132 for 4 h before harvesting, and the Flag-precipitates (IP:Flag) were blotted with anti-polyubiquitin (FK2), anti-BAG6, and anti-Flag antibodies. Mock indicates empty vector transfection. Note that UBQLN4-BAG6 co-precipitation can be observed exclusively in the presence of polyubiquitinated substrates.",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(B, C) Puromycin-treated cells with UBQLN4 siRNA contain increased number of ALIS. At 72 h after transfection of the two distinct siRNA duplexes for UBQLN4 (UBQLN4 siRNA#1 and #2) or control siRNA (5 nM each), the cells were treated with 5 µg/mL puromycin for 2 h, and then subjected to immunostaining with an anti-polyubiquitin FK2 antibody (shown in green, B) as in (A). The number of ALIS was determined. The quantified data in (C) represent mean ± SEM. n = 76 cells for control siRNA, n = 89 cells for UBQLN4 siRNA#1, and n = 81 cells for UBQLN4 siRNA #2. P‐values were calculated by Welch's t-test between the siRNA‐transfected and the respective control condition (*P < 0.01).",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(B, C) Puromycin-treated cells with UBQLN4 siRNA contain increased number of ALIS. At 72 h after transfection of the two distinct siRNA duplexes for UBQLN4 (UBQLN4 siRNA#1 and #2) or control siRNA (5 nM each), the cells were treated with 5 µg/mL puromycin for 2 h, and then subjected to immunostaining with an anti-polyubiquitin FK2 antibody (shown in green, B) as in (A). The number of ALIS was determined. The quantified data in (C) represent mean ± SEM. n = 76 cells for control siRNA, n = 89 cells for UBQLN4 siRNA#1, and n = 81 cells for UBQLN4 siRNA #2. P‐values were calculated by Welch's t-test between the siRNA‐transfected and the respective control condition (*P < 0.01).",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(D) Depletion of UBQLN4 makes HeLa cells more sensitive to puromycin-induced cell death. After 48 h of UBQLN4 siRNA treatment, the cells were treated with 5 µg/mL puromycin for 15.5 h and then viability was measured. The data represent mean ± SD calculated from 3 independent experiments (n=3). P‐values were calculated by Student's t-test compared with puromycin-treated control siRNA cells (*P < 0.01).",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(B) IL-2Rα ΔSS mislocalized to the cytosolic fraction. HeLa cells, expressing Flag-tagged IL-2Rα WT or ΔSS, were fractionated to the cytosolic (Cyt.) and membrane (Mem.) fractions. Tubulin was used as a cytoplasmic marker, while calnexin was used for the ER membrane fraction.",
    "ncbi_link": "IL-2Rα: 3559"
  },
  {
    "caption": "(C) IL-2Rα ΔSS was not glycosylated. Flag-tagged IL-2Rα WT or ΔSS proteins was expressed in HeLa cells, and immunoprecipitated with an anti-Flag antibody. The precipitates were incubated with (+) or without (-) 10 unit of the deglycosylation enzyme PNGase F for 2 h, and subjected to western blot analysis with an anti-Flag antibody. Glycosylated and non-glycosylated signals are indicated.",
    "ncbi_link": "IL-2Rα: 3559"
  },
  {
    "caption": "(D) The glycosylated form of IL-2Rα WT is a stable protein, while mislocalized IL-2Rα ΔSS is degraded rapidly via its TMD. A series of IL-2Ra deletion proteins were expressed in HeLa cells and then chased with 20 μg/mL CHX for the indicated periods. Actin was used as a loading control. The right panel is a quantified graph of the left blot signals represent mean ± SD calculated from 4 independent experiments (n=4).",
    "ncbi_link": "IL-2Ra: 3559
IL-2Rα: 3559"
  },
  {
    "caption": "(F) The Flag-tagged IL-2Rα ΔSS mutant and T7-tagged ubiquitin were co-expressed in HeLa cells and the cells were treated with (+) or without (-) 10 μM MG-132. After 4 h, Flag-precipitates were blotted with anti-T7 and anti-Flag antibodies.",
    "ncbi_link": "IL-2Rα: 3559"
  },
  {
    "caption": "(G) HeLa cells expressing Flag-tagged IL-2RaWT, ΔSS, and ΔSSΔTM proteins were treated with (+) or without (-) 10 μM MG-132. At 4 h after MG-132 treatment, the cells were lysed and analyzed by immunoblotting using the indicated antibodies. Note that a higher migrating form of non-glycosylated (and thus defective) IL-2Ra WT (indicated by the arrowhead) is detected strongly in the presence of MG-132.",
    "ncbi_link": "IL-2Ra: 3559"
  },
  {
    "caption": "(A, B) IL-2Rα ΔSS is stabilized in UBQLN4-knockdown cells. HeLa cells were transfected with three distinct siRNA duplexes for UBQLN4 (UBQLN4 siRNA#1~#3) or control siRNA. At 48 h after siRNA transfection, Flag tagged-IL-2Rα ΔSS was expressed in the cells. At 24 h after IL-2RaSS transfection, the cells were chased with 20 μg/mL CHX and harvested at the indicated time after CHX addition. Anti-Flag signals in the control or UBQLN4 siRNA-treated cells (siRNA#1~#3) were quantified at the indicated time points. The data represent mean ± SEM calculated from 4 independent experiments (n=4). The UBQLN4 signal is marked by an arrowhead, while the band just below it (indicated by an asterisk) is a non-specific band, since this signal was never affected by any of the UBQLN4 siRNAs. Actin was used as a loading control.",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(C) Polyubiquitin modification of IL-2Rα ΔSS was not diminished, but rather strengthened, in UBQLN4 knockdown cells. At 48 h after transfection of HeLa cells with siRNA for UBQLN4 or BAG6, Flag-tagged IL-2Rα ΔSS and T7-tagged ubiquitin were expressed with (+) or without (-) 10 mM MG-132. From these cells, Flag-tagged IL-2Rα ΔSS was affinity-purified using Hot lysis analysis, and Flag-precipitates were blotted with an anti-T7 antibody to detect polyubiquitination of IL-2Rα ΔSS.",
    "ncbi_link": "BAG6: 7917
UBQLN4: 56893"
  },
  {
    "caption": "(A) A series of Flag-tagged truncated mutants of IL-2Ra substrates were expressed in HeLa cells with T7-tagged UBQLN4 and treated with (+) or without (-) 10 µM MG-132 for 4 h. Flag-IL-2Ra substrates were immunoprecipitated and their co-precipitation with UBQLN4 was analyzed.",
    "ncbi_link": "IL-2Ra: 3559"
  },
  {
    "caption": "(B) T7-UBQLN4 was immunoprecipitated, and its interactions with a series of IL-2Ra proteins were detected.",
    "ncbi_link": "IL-2Ra: 3559"
  },
  {
    "caption": "(B) UBQLN4 dominantly co-precipitates IL-2Rα ΔSS over UBQLN1. Precipitates of Flag-tagged UBQLN1 or UBQLN4 from HeLa cell lysates were probed with IL-2Rα ΔSS.",
    "ncbi_link": "UBQLN1: 29979
UBQLN4: 56893"
  },
  {
    "caption": "(E) Substitution of the STI-II sequence of UBQLN4 with that of UBQLN1 (designated as the 4-STI-II-1 mutant protein) abolished its high affinity to the IL-2Rα ΔSS client protein.",
    "ncbi_link": "UBQLN1: 29979
UBQLN4: 56893"
  },
  {
    "caption": "(F) Substitution of the STI-II sequence of UBQLN1 with that of UBQLN4 (designated as the 1-STI-II-4) did not enable UBQLN1 to recognize IL-2Rα ΔSS.",
    "ncbi_link": "UBQLN1: 29979
UBQLN4: 56893"
  },
  {
    "caption": "(B, C and D) The wild-type (WT) form of Flag-tagged UBQLN4 and its truncated derivatives were expressed in HeLa cells with T7-tagged IL-2RαΔSS (B and C). At 4 h after the addition of 10 μM MG-132, UBQLN4 was immunoprecipitated with an anti-Flag antibody and the precipitates were blotted with an anti-T7 antibody.",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(B, C and D) The wild-type (WT) form of Flag-tagged UBQLN4 and its truncated derivatives were expressed in HeLa cells with T7-tagged IL-2Rα ΔSS (B and C) and T7-tagged ubiquitin (D). At 4 h after the addition of 10 μM MG-132, UBQLN4 was immunoprecipitated with an anti-Flag antibody and the precipitates were blotted with an anti-T7 antibody.",
    "ncbi_link": "UBQLN4: 56893"
  },
  {
    "caption": "(E) GST-tagged and purified UBQLN4 and its truncated derivatives (ΔUBA and ΔSTI-II) were incubated with K48-linked polyubiquitin chains. After in vitro GST pull-down, the precipitates were probed with an anti-polyubiquitin (FK2) antibody.",
    "ncbi_link": "UBQLN4: 94232"
  },
  {
    "caption": "(A) UBQLN4 interacts with non-glycosylated (and thus defective) IL-2Ra WT in SRP54-knockdown cells. After treatment of HeLa cells with SRP54 siRNA (10 nM) for 48 h, Flag-tagged IL-2RaWT and T7-tagged UBQLN4 proteins were expressed, and the cells were treated with (+) or without (-) 10 µM MG-132 at 4 h before harvesting. UBQLN4 was affinity-purified from cell extracts and probed with an anti-Flag antibody. Note that the levels of non-glycosylated IL-2RaWT (indicated as Defective) increased, while the glycosylated form of this protein (indicated as Assembled) decreased in SRP54 knockdown cells.",
    "ncbi_link": "SRP54: 6729"
  },
  {
    "caption": "(B, C) SRP54 knockdown stimulates polyubiquitinated proteins co-precipitation of UBQLN4. Flag-tagged UBQLN4 and T7-tagged ubiquitin were expressed in SRP54 siRNA-treated cells, and Flag precipitates were probed with an anti-T7 antibody to detect polyubiquitinated clients co-precipitation with UBQLN4 under no addition of MG-132 (B). Note that the interaction of UBQLN4 with polyubiquitinated substrates was further increased in SRP54 knockdown cells treated with MG-132 for 4 h before harvesting (C).",
    "ncbi_link": "SRP54: 6729
UBQLN4: 56893"
  },
  {
    "caption": "(A, B) Wild-type (WT) (BY4741) cells expressing GFP−Atg8 were grown to mid-log-phase in YPD and were then preincubated with 50 µM cerulenin or 50 µM cerulenin + 0.1 mM palmitic/stearic/myristic acids or with DMSO (-) in the rich medium for 30 min. Cells were washed and shifted to nitrogen-starvation medium (SD-N) for 4 h in the presence of 50 µM cerulenin or 50 µM cerulenin + 0.1 mM palmitic/stearic/myristic acids or DMSO. Cells were then lysed and subjected to SDS−PAGE, followed by western blot analysis using anti-GFP and anti-Pgk1 antibodies (A),",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(A, B) Wild-type (WT) (BY4741) cells expressing GFP−Atg8were grown to mid-log-phase in YPD and were then preincubated with 50 µM cerulenin or 50 µM cerulenin + 0.1 mM palmitic/stearic/myristic acids or with DMSO (-) in the rich medium for 30 min. Cells were washed and shifted to nitrogen-starvation medium (SD-N) for 4 h in the presence of 50 µM cerulenin or 50 µM cerulenin + 0.1 mM palmitic/stearic/myristic acids or DMSO. Cells were then lysed and subjected to SDS−PAGE, followed by western blot analysis using anti-GFP and anti-Pgk1 antibodies (A), or were visualized by fluorescence microscopy (B)",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(C) Cells (TOS038) expressing Atg1-GFP were grown to mid-log phase and were then preincubated in YPD with 50 µM cerulenin or with DMSO for 30 min. Cells were washed, shifted to SD-N for 4 h, and then visualized by fluorescence microscopy. Scale bar, 5 μm.",
    "ncbi_link": "Atg1: 852695"
  },
  {
    "caption": "(D) WT (BY4741) and pep4∆ (TOS015) strains were grown to mid-log phase and preincubated in YPD with cerulenin or DMSO for 30 min. Cells were pulse-labeled for 10 min with [35S] methionine and cysteine and chased for the indicated time periods. Cell lysates were subjected to immunoprecipitation with anti-Ape1 antibodies followed by SDS‒PAGE and X-ray film to detect radioactive signals. prApe1, premature Ape1; mApe1, mature Ape1. (",
    "ncbi_link": "pep4: 855949"
  },
  {
    "caption": "(E) Cells of the fas1∆ (TOS029) strain expressing GFP‒Atg8 were grown to mid-log phase in YPD + 0.1 mM palmitic/stearic/myristic acids and shifted either to the same medium or to YPD without fatty acids for 30 min. Cells were then shifted to SD-N for the indicated times. Cell lysates were subjected to SDS‒PAGE, followed by western blot analysis using anti-GFP antibodies.",
    "ncbi_link": "Atg8: 852200
fas1: 853653"
  },
  {
    "caption": "(C) WT (SCY62) and tagΔsteΔ (H1246) cells were grown to mid-log phase in YPD and shifted to SD-N for 3 h. Cells were stained with Nile red and visualized by fluorescence microscopy. Scale bar, 5 μm.",
    "ncbi_link": "ste: 
tag: "
  },
  {
    "caption": "(D) WT (SCY62) and tag∆ste∆ (H1246) cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for the indicated time periods. Cell lysates were subjected to SDS−PAGE, followed by western blot analysis using anti-GFP, anti-Ape1 (prApe1, premature Ape1; mApe1, mature Ape1), and anti-Fas1 and anti-Pgk1 antibodies.",
    "ncbi_link": "ste: 
tag: 
Atg8: 852200"
  },
  {
    "caption": "(E) WT (SCY62) and tag∆ste∆ (H1246) cells were grown to mid-log phase in YPD and shifted to SD-N for 2 h. GFP−Atg8 was visualized by fluorescence microscopy. Scale bar, 5 μm. cer, cerulenin; DIC, Differential interference contrast; FA, fatty acids; SD-N, nitrogen-starvation medium; WT, wild-type, YPD, complete medium.",
    "ncbi_link": "ste: 
tag: "
  },
  {
    "caption": "(A) GAL-DGA1GAL-ARE2lro1Δ are1Δ (FYS118 strain) was grown on SC (synthetic minimal medium without dextrose) + raffinoseovernight, diluted to OD 0.4, and grown to mid-log phase in either SC + glucose or SC + galactose medium. Cells were shifted to SD-N for 2 h, stained with BODIPY, and visualized by fluorescencemicroscopy. Scale bar, 5 μm.",
    "ncbi_link": "GAL: 
are1: 850415
ARE2: 855753
DGA1: 854419
lro1: 855742"
  },
  {
    "caption": "(B) WT (BY4741) and GAL-DGA1 GAL-ARE2 lro1∆ are1∆ (FYS118) cells expressing GFP−Atg8 were grown as in A. Cells were lysed at the indicated times and subjected to SDS‒PAGE, followed by western blot analysis using anti-GFP antibodies. (",
    "ncbi_link": "GAL: 
are1: 850415
ARE2: 855753
Atg8: 852200
DGA1: 854419
lro1: 855742"
  },
  {
    "caption": "(C, D) WT (BY4741) and GAL-DGA1 GAL-ARE2 lro1∆ are1∆ (FYS118) cells expressing GFP−Atg8 (C) or GFP−Atg1 (D) were grown as in A and visualized by fluorescence microscopy after 2 h in SD-N. Scale bar, 5 μm. DIC, Differential interference contrast; SD-N, nitrogen-starvation medium; WT, wild-type.",
    "ncbi_link": "GAL: 
are1: 850415
ARE2: 855753
Atg1: 852695
Atg8: 852200
DGA1: 854419
lro1: 855742"
  },
  {
    "caption": "(A) WT (SCY62), tag∆ste∆ (H1246), tag∆ (H1226) and ste∆ (H1112) cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for 6 h. Cells were stained with BODIPY and visualized by fluorescence microscopy. Scale bar, 5 μm.",
    "ncbi_link": "ste: 
tag: 
Atg8: 852200"
  },
  {
    "caption": "(A) WT (SCY62), tag∆ste∆ (H1246), tag∆ (H1226) and ste∆ (H1112) cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for the indicated time periods. Cells were lysed and subjected to SDS−PAGE, followed by western blot analysis using anti-GFP antibodies. (B) Quantification of the GFP/GFP−Atg8 ratio. Error bars represent the s.e.m. of three independent experiments. *P < 0.05 (Student's t-test). (",
    "ncbi_link": "ste: 
tag: 
Atg8: 852200"
  },
  {
    "caption": ". (C) WT (SCY62), tag∆ste∆ (H1246), tag∆ (H1226) and ste∆ (H1112) cells expressing GFP-Atg8 were grown to mid-log phase in YPD and shifted to SD-N for 2 h. GFP−Atg8 was visualized by fluorescence microscopy. Scale bar, 5 μm. (",
    "ncbi_link": "ste: 
tag: 
Atg8: 852200"
  },
  {
    "caption": "(D) WT (SCY62), tag∆ste∆ (H1246), tag∆ (H1226) and ste∆ (H1112) cells were grown as in (A). Lysates were subjected to SDS−PAGE in urea gel, followed by western blot analysis using anti-Atg8 and anti-Pgk1 antibodies. Atg8 I, non-lipidated Atg8; Atg8 II, lipidated Atg8. DIC, Differential interference contrast; SD-N, nitrogen-starvation medium; WT, wild type.",
    "ncbi_link": "ste: 
tag: "
  },
  {
    "caption": "Fig. 6 Lack of lipid droplets inhibits starvation-induced formation of autophagosomes. (A, H) WT pep4∆ (pep4∆) (A,B), tag∆ste∆ pep4∆ (tag∆ste∆pep4∆)(C,D), ste∆ pep4∆ (ste∆pep4∆)(E,F) and tag∆ pep4∆ (tag∆pep4∆) (G,H) cells were grown to an exponential phase in YPD before being starved in SD-N for 2 h, and were then processed for electron microscopy. H is a magnification of the box in panel G. Magnification of proliferating ER in a tag∆ste∆ (H1246) cell is shown in (I) Asterisks indicate autophagic bodies. N, nucleus; PM, plasma membrane; CW, cell wall; ER, endoplasmic reticulum; M, mitochondrion; V, vacuole; #, trehalose; F, ER proliferation. Scale bars: 1 µm (A-H) and 200 nm (I). (J) Average number of autophagic bodies per cell section was determined by counting 100 randomly selected cell profiles. Error bars represent standard deviations fromcounting of the three grids. ***P < 0.001 (Student's t-test). SD-N,nitrogen-starvation medium; WT, wild type YPD, complete medium.",
    "ncbi_link": "ste: 
tag: 
pep4: 855949"
  },
  {
    "caption": "(A) WT (BY4741), tgl1∆, yeh1∆ ,and yeh2∆ cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for the indicated time periods. Cells were lysed and subjected to SDS−PAGE, followed by western blot analysis using anti-GFP antibodies. Quantification of the GFP/GFP−Atg8 ratio is presented on the right. Error bars represent the s.e.m. of three independent experiments. *P < 0.05 (Student's t-test).",
    "ncbi_link": "Atg8: 852200
tgl1: 853717
yeh1: 850648
yeh2: 850707"
  },
  {
    "caption": "(B) WT (BY4741) and tgl3∆tgl4∆tgl5∆ cells expressing GFP−Atg8 were grown, treated, lysed, and western blotted as in (A). Quantification of the GFP/GFP−Atg8 ratio is presented on the right. Error bars represent the s.e.m. of three independent experiments. *P < 0.05 (Student's t-test). (",
    "ncbi_link": "Atg8: 852200
tgl3: 855361
tgl4: 853964
tgl5: 854248"
  },
  {
    "caption": "(C) WT (BY4741), ayr1∆ and ldh1∆ cells expressing GFP−Atg8 were grown, treated, lysed, and western blotted as in (A). Quantification of the GFP/GFP−Atg8 ratio is presented on the right. Error bars represent the s.e.m. of three independent experiments. *P < 0.05 (Student's t-test).",
    "ncbi_link": "Atg8: 852200
ayr1: 854682
ldh1: 852503"
  },
  {
    "caption": "(D) WT (BY4741), ldh1∆ayr1∆ cells expressing GFP−Atg8 were grown, treated, lysed, and western blotted as in (A). Quantification of the GFP/GFP−Atg8 ratio is presented on the right. Error bars represent the s.e.m. of three independent experiments. **P < 0.01 (Student's-t test).",
    "ncbi_link": "Atg8: 852200
ayr1: 854682
ldh1: 852503"
  },
  {
    "caption": "(E) WT (BY4741), ice2∆ and ldb16∆ cells expressing GFP−Atg8 were grown, treated, lysed, and western blotted as in (A). Quantification of the GFP/GFP−Atg8 ratio is presented on the right. Error bars represent the s.e.m. of three independent experiments. *P < 0.05, **P < 0.01 ***P < 0.001 (Student's t-test).",
    "ncbi_link": "Atg8: 852200
ice2: 854718
ldb16: 850351"
  },
  {
    "caption": "(F) WT (BY4741), ice2∆ and yeh1∆ cells expressing GFP−Atg8 were grown to mid-log phase in YPD and shifted to SD-N for 4 h. GFP−Atg8 was visualized by fluorescence microscopy. Scale bar, 5 μm. DIC, Differential interference contrast; SD-N, nitrogen-starvation medium; WT, wild type.",
    "ncbi_link": "Atg8: 852200
ice2: 854718
yeh1: 850648"
  },
  {
    "caption": "A. The survival of age- and sex-matched HDAC6+/+ mice and HDAC6-/- mice was monitored for 9 days after intravenous VSV-Indiana infection (2 × 108 pfu/mouse; n = 12 per group; log-rank test).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "B. Determination of the viral load in organs by standard plaque assay. HDAC6+/+ and HDAC6-/- mice were intravenously infected with VSV-Indiana, and the brain and spleen were collected at 5 dpi (2 × 108 pfu/mouse; n = 6 per group; Mann-Whitney test).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "C. Determination of viral loads in organs by Q-PCR of VSV viral transcripts. The brain and spleen were collected at 5 dpi after HDAC6+/+and HDAC6-/- mice were intravenously infected with VSV-Indiana (2 × 108 pfu/mouse; n = 9 per group; Mann-Whitney test).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "D. The viral load in the serum was assessed by standard plaque assay. HDAC6+/+ and HDAC6-/- mice were intravenously infected with VSV-GFP. Serum was collected at the indicated time points and analyzed (4 × 108 pfu/mouse; n = 3 per group; Student's t-test).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "F. ELISA of serum IFN-β (left) and IL-6 (right) after poly(I:C) injection. HDAC6+/+ and HDAC6-/- mice were intravenously injected with poly(I:C). Serum was collected at the indicated time points and analyzed (200 μg/mouse; n = 3 per group; Student's t-test).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "A, B. virus replication at 12 and 24 hpi, in HDAC6+/+ and HDAC6-/- BMDMs in response to VSV-GFP (MOI = 10) infection (A) and PR8-GFP (MOI = 5) infection (B).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "C. Virus replication in HDAC6+/+ and HDAC6-/- BMDMs in response to HSV-GFP (MOI = 2) infection.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "D. Virus replication in HDAC6+/+ and HDAC6-/- PBMCs in response to VSV-GFP (MOI = 10) infection.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "E. ELISA of IFN-β (upper), IL-6 (lower) levels in the supernatant of (A) and (B), and in HDAC6+/+ and HDAC6-/- BMDMs treated with poly(I:C) (20 µg/ml) or transfected with 5'ppp-dsRNA (1 µg/ml).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "F. Immunoblot analysis of the phosphorylated and inactive forms of IRF3, IKBα, TBK1, RIG-I, MAVS, HDAC6, and β-actin at the indicated times (0, 2, 4, 8, and 16 h) in HDAC6+/+ and HDAC6-/- BMDMs. BMDMs were stimulated with PR8-GFP (MOI = 3).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "G. Induction of mRNA for type I IFN, IL-6, and other IFN-related antiviral genes in HDAC6+/+ and HDAC6-/- BMDMs in response to a RIG-I agonist stimulation at 6 h. HDAC6+/+ and HDAC6-/- BMDMs were stimulated with 5'ppp-dsRNA (0.5 µg/ml) for 6 h.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "A, B. Fluorescence microscopy at 24 hpi showing green fluorescence absorbance at 12 and 24 hpi, and virus replication at 12 and 24 hpi, in control and HDAC6 knockdown RAW264.7 cells in response to VSV-GFP (MOI = 1) infection (A) and PR8-GFP (MOI = 1) infection (B). bar, 100µm",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "C. ELISA of IFN-β (upper), IL-6 (lower) levels in the supernatant of (A) and (B), and in control and HDAC6 knockdown RAW264.7 cells treated with poly(I:C) (20 µg/ml) or transfected with 5'ppp-dsRNA (1 µg/ml).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "D, E. Fluorescence microscopy at 24 hpi showing green fluorescence absorbance at 12 and 24 hpi, and virus replication at 12 and 24 hpi, in HDAC6+/+ and HDAC6-/- MEFs in response to VSV-GFP (MOI = 1) infection (D) and PR8-GFP (MOI = 1) infection (E). bar, 50µm",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "F. ELISA of IFN-β (upper), IL-6 (lower) levels in the supernatant of (D) and (E), and in HDAC6+/+ and HDAC6-/- MEFs transfected with poly(I:C) (1 µg/ml).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "A, B. Fluorescence microscopy at 24 hpi showing green fluorescence absorbance at 12 and 24 hpi, and virus replication at 12 and 24 hpi, in vector, HDAC6, or HDAC6-CDM-overexpressing stable RAW264.7 cells in response to VSV-GFP (MOI = 1) infection (A) and PR8-GFP (MOI = 1) infection (B). bar, 100µm.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "C. ELISA of IFN-b (upper) and IL-6 (lower) levels in the supernatant of (A), (B), and in vector, HDAC6, or HDAC6-CDM-overexpressing stable RAW264.7 cells treated with poly(I:C) (20 μg/ml) or transfected with 5'ppp-dsRNA (1 µg/ml).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "D, E. Luciferase assay in 293T cells transfected with an IFN-β luciferase promoter and TK-Renilla together with mutant HDAC6 or HDAC6-CDM (100, 200, 400, or 800 ng), followed by PR8-GFP (MOI = 2) infection (D) or by poly(I:C) (E) (1 μg/ml) transfection for another 12 h.",
    "ncbi_link": "luciferase: 
TK-Renilla: 
HDAC6: 15185"
  },
  {
    "caption": "F, G. Luciferase assay in 293T cells transfected with RIG-I (F), MDA-5 (G), an IFN-β luciferase promoter, and TK-Renilla together with mutant HDAC6 or HDAC6-CDM (100, 200, 400, or 800 ng). 24 h later, IFN-β activity was measured by luciferase reporter assay.",
    "ncbi_link": "luciferase: 
TK-Renilla: 
HDAC6: 15185"
  },
  {
    "caption": "B. BMDMs were isolated from HDAC6+/+ and HDAC6-/- mice and were transfected with 5ˊppp-dsRNA. Whole cell lysates were prepared after 8 h of transfection and co-immunoprecipitation analysis of RIG-I and HDAC6 was performed.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "D. Fluorescence microscopy, green fluorescence absorbance and virus replication at 24hpi in RIG-I+/+ and RIG-I-/- MEFs. Cells were transfected with si-HDAC6 and si-control for 36 h, followed infection with VSV-GFP (MOI = 1). bar, 100µm.",
    "ncbi_link": "RIG-I: 230073
HDAC6: 15185"
  },
  {
    "caption": "E. HDAC6+/+, HDAC6-/- MEFs, and HDAC6-/- MEFs reconstituted with HDAC6 wild-type were subjected to immunoprecipitation using an anti-RIG-I antibody and immunoblotted with anti-acetyl-lysine and anti-RIG-I antibodies. Acetyl-tubulin was measured in total lysates to determine HDAC6 deacetylase activity.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "F. Whole cell lysates from HDAC6+/+ and HDAC6-/- MEFs were prepared and used in dsRNA pull-down assays. Pull-down samples were analyzed by western blotting with anti-RIG-I, anti-HDAC6, and anti-β-actin antibodies. Intensity of pull-downed RIG-I was quantified.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "G. Whole cell lysates from HDAC6-/- MEFs and HDAC6-/- MEFs reconstituted with HDAC6 wild-type and HDAC6-CDM were prepared and used in dsRNA pull-down assays. Samples were analyzed by western blotting with anti-RIG-I and anti-HDAC6 antibodies. Intensity of pull-downed RIG-I was quantified.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "C. A luciferase assay was performed using 293T cells transfected with the IFN-βluciferase promoter and TK-Renilla together with 2 ng of RIG-I wild-type, RIG-I 858Q, RIG-I 858R, RIG-I K909Q, or RIG-I K909R mutant, followed by transfection with poly(I:C) (1 μg/ml) for another 12 h.",
    "ncbi_link": "luciferase: 
TK-Renilla: 
RIG-I: 230073"
  },
  {
    "caption": "D. Fluorescence microscopy, green fluorescence absorbance, and virus replication at 24 hpi in RIG-I-/- MEFs. Cells were transiently transfected with empty vector, RIG-I wild-type, RIG-I K909Q, or RIG-I K909R mutant for 24 h, followed infection with VSV-GFP (MOI = 1). bar, 100µm",
    "ncbi_link": "RIG-I: 230073"
  },
  {
    "caption": "E. HDAC6-/- MEFs were transfected with the indicated expression plasmids. At 1 day post-transfection, whole cell lysates were prepared and used in dsRNA pull-down assays. Pull-down samples were analyzed by western blotting with anti-RIG-I and anti-β-actin antibodies.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "F. 293T cells were transfected with 2 μg of FLAG-tagged RIG-I and 1, 5, or 10 μg of V5-tagged HDAC6. At 36 h post-transfection, whole cell lysates were prepared for co-immunoprecipitation analysis of V5-tagged HDAC6 and acetylated K909 (on RIG-I wild-type). Samples were analyzed by western blotting with a K909 acetylation-specific antibody.",
    "ncbi_link": "RIG-I: 230073
HDAC6: 15185"
  },
  {
    "caption": "G. 293T cells were transfected with 2 μg of FLAG-tagged RIG-I. At 24 h post-transfection, cells were infected with VSV-GFP (MOI = 0.1). At 2 and 4 h post-infection, whole cell lysates were prepared for immunoprecipitation analysis of acetylated K909 (on RIG-I wild-type). Samples were analyzed by western blotting with a K909 acetylation-specific antibody. Intensity of ac-909K normalized to Flag-RIG-I was quantified.",
    "ncbi_link": "RIG-I: 230073"
  },
  {
    "caption": "(a) Immunoblot analysis of caspase-1 and IL-1β in lysates (Lys) and supernatants (Sup) of peritoneal macrophages obtained from Map1lc3b-/- mice and Becn1+/- mice and the corresponding wild-type littermate mice, then left unstimulated (-) or stimulated with LPS alone (LPS) or LPS followed by 30 min of ATP treatment (L + A). p10, mature form of caspase-1. Right margin, molecular size in kilodaltons (kDa).",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(c) Immunoblot analysis of caspase-1 and IL-1β in lysates (left) and ELISA of cytokines in supernatants (right) of Map1lc3b+/+ and Map1lc3b-/- BMDMs incubated with LPS, followed by 30 min (immunoblot) or 1 h (ELISA) of ATP treatment.",
    "ncbi_link": "Map1lc3b: 67443"
  },
  {
    "caption": "(d) ELISA of IL-1β secretion by LPS-primed Map1lc3b-/- mice and Becn1+/- BMDMs incubated for 1 h with z-YVAD-fmk (z-YVAD; 10 μM) or vehicle (dimethylsulfoxide (DMSO)), followed by stimulation for 1 h with ATP. *P 0.05 (Student's t-test). Data are representative of three or four experiments (mean and s.d. in b-d).",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(a,b) Transmission electron microscopy of morphological changes in mitochondria (arrows) in Map1lc3b−/− BMDMs (a) or Becn1+/− BMDMs (b) left untreated or incubated for 6 h with LPS (10 ng/ml) and then stimulated for 30 min with ATP (1 mM). Outlined areas (middle) enlarged at right. Scale bars, 500 nm.",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(c) Flow cytometry of Map1lc3b−/− and Becn1+/− macrophages left unstained or labeled with MitoSOX.",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(g,h) ELISA of IL-1β secretion (left) and immunoblot analysis for caspase-1 in lysates (right) of Map1lc3b+/+ and Map1lc3b−/− (g) or Becn1+/+ and Becn1+/− (h) peritoneal macrophages incubated for 1 h with Mito-TEMPO (500 μM), followed by LPS and ATP. *P 0.05 (Student's t-test). Data represent three experiments (mean and s.d. in a,c,d-h).",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(a) ELISA of cytokine secretion by LPS-primed Map1lc3b+/+ and Map1lc3b−/− BMDMs incubated with cyclosporine A or DMSO, followed by stimulation for 1 h with ATP.",
    "ncbi_link": "Map1lc3b: 67443"
  },
  {
    "caption": "(b) ELISA of cytokine secretion by LPS-primed Becn1+/+ or Becn1+/− BMDMs incubated with cyclosporine A (10 μM) or DMSO, followed by ATP stimulation.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(f) Quantitative PCR analysis of cytosolic mtDNA in LPS-primed Map1lc3b−/− and Becn1+/− BMDMs stimulated for 30 min with ATP. The amount of cytosolic mtDNA is presented relative to the amount in untreated control cells, set as 1. *P 0.05 (Student's t-test). Data are representative of three experiments (mean and s.d.).",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(c) ELISA of IL-1β secretion by Aim2+/+ and Aim2−/− BMDMs primed for 4 h with LPS (200 ng/ml), then transfected for 6 h with 1 μg mtDNA (through the use of liposomes as the vehicle), followed by stimulation for 1 h with ATP. *P 0.05, versus Aim2−/− cells treated with LPS and ATP (Student's t-test).",
    "ncbi_link": "Aim2: 383619"
  },
  {
    "caption": "(d) ELISA of cytokine secretion by LPS-primed Aim2−/− BMDMs transfected for 6 h with mtDNA, poly(dA:dT) or mtDNA predigested by DNase I (+ DNase; far left), followed by stimulation for 1 h with ATP. *P 0.05 (Student's t-test). Data are representative of three experiments (mean and s.d.).",
    "ncbi_link": "Aim2: 383619"
  },
  {
    "caption": "(a) Cytokine secretion by LPS-primed Map1lc3b+/+ and Map1lc3b−/− (a) or Becn1+/+ and Becn1+/− (b) peritoneal macrophages incubated for 15 min with glybenclamide (Glyb; 100 μM (a) or 50-100 μM (b)), Bay 11-7082 (Bay; 12 μM) or DMSO (-), followed by ATP.",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(c) Cytokine secretion by LPS-primed wild-type (WT) and NALP3-deficient (NALP3-KO) macrophages incubated with rotenone, followed by stimulation for 1 h with ATP.",
    "ncbi_link": "NALP3: 216799"
  },
  {
    "caption": "(d) Quantitative PCR analysis of cytosolic mtDNA in wild-type and NALP3-deficient BMDMs left unstimulated (-) or stimulated with LPS, followed by treatment for 15 or 30 min with ATP (left), and immunoblot analysis of cytosolic cytochrome c and activation of caspase-1 in the cells at left (right).",
    "ncbi_link": "NALP3: 216799"
  },
  {
    "caption": "(e) Quantitative PCR analysis of cytosolic mtDNA in LPS-primed wild-type, NALP3-deficient or ASC-deficient (ASC-KO) BMDMs stimulated for 15 min with ATP. *P 0.05, NALP3-deficient or ASC-deficient versus wild-type treated with LPS and ATP (Student's t-test).",
    "ncbi_link": "NALP3: 216799
ASC: 66824"
  },
  {
    "caption": "(h) Flow cytometry of LPS-primed wild-type, ASC-deficient and NALP3-deficient peritoneal macrophages stimulated for 30 min with ATP and stained with annexin V. Data represent three experiments (mean and s.d. in a-e).",
    "ncbi_link": "NALP3: 216799
ASC: 66824"
  },
  {
    "caption": "(a) ELISA of serum IL-1β and IL-18 at 24 h after intraperitoneal injection of LPS (12 mg per kg body weight) into male Map1lc3b+/+ and Map1lc3b−/− mice.",
    "ncbi_link": "Map1lc3b: 67443"
  },
  {
    "caption": "(b) Survival of Map1lc3b+/+ mice (n = 11) and Map1lc3b−/− mice (n = 10) after LPS challenge (100 mg per kg body weight), assessed over a period of 2 weeks.",
    "ncbi_link": "Map1lc3b: 67443"
  },
  {
    "caption": "(c,d) ELISA of serum IL-1β and IL-18 in male Map1lc3b+/+ and Map1lc3b−/− mice (c) and Becn1+/+ and Becn1+/− mice (d) at 24 h after CLP or sham laparotomy. In a,c,d, each symbol represents an individual mouse; small horizontal lines indicate the mean. P values, unpaired two-tailed Student's t-test (a,c,d) or log-rank test (b). Data are representative of two experiments.",
    "ncbi_link": "Becn1: 56208
Map1lc3b: 67443"
  },
  {
    "caption": "(A) Family pedigree. Variant segregation analysis of PSMC3. Electropherogram of a part of intron 10 of PSMC3 encompassing the identified variation (c.[1127+337A>G];[1127+337A>G], p.[(Ser376Arg15*)];[(Ser376Arg15*)]) in the affected individuals, their unaffected parents and siblings. The variation was found at the homozygous state in the affected individuals (II.2, II.4, II.7), at the heterozygous state in the parents (I.1, I.2, I.3, I.4, I.5, I.6) and was either at the heterozygous state (II.5) or absent in the unaffected siblings (II.1, II.3, II.6).",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(E) Amplification of the cDNA fragment between exons 9-10 and 11 of PSMC3 showing the abnormally spliced RNA fragment. One band at 180bp representing the normal allele is seen for the control and two bands for the individual II.4 (pathologic allele at 300bp).",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(D) Proteins extracted from control and CI PSMC3 were separated by 10 or 12.5% SDS-PAGE prior to western-blotting using primary antibodies directed against ubiquitin and several proteasome subunits and/or components including α6, β1, β; β5, β5i, Rpt2 (PSMC1), Rpt5 (PSMC3), Rpt3 (PSMC4), Rpt4 (PSMC6) and PA28-α, as indicated. For the PSMC3 staining, two exposure times are shown. Arrow indicates an additional PSMC3 species corresponding to the expected size of the truncated PSMC3 variant. Equal protein loading between samples was ensured by probing the membrane with an anti-α-Tubulin antibody.",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "Control and patient (index case, IC PSMC3) fibroblasts were exposed to a 16-h treatment with 30 nM of the proteasome inhibitor carfilzomib or left untreated (as a negative control). Following treatment, cells were collected and subjected to RIPA-mediated protein extraction prior to SDS-PAGE and subsequent western-blotting using antibodies specific for ubiquitin, TCF11/Nrf1, Rpt1 (PSMC2), Rpt3 (PSMC4), Rpt5 (PSMC3), Rpt6 (PSMC5), β1, β2, β5, β5i, β1i, PA28-α and α-Tubulin (loading control) as indicated. For the TCF11/Nrf1 staining, two exposure times are shown.",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(A) Control and/or patient (index case, IC PSMC3) fibroblasts were subjected to a 24-h transfection with pcDNA3.1/empty vector (mock) or pcDNA3.1/PSMC3 prior to RIPA-mediated protein extraction and subsequent western-blotting using antibodies specific for ubiquitin, PSMC3 (i.e. Rpt5) and α-Tubulin (loading control).",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(B) Densitometry analysis showing the relative ubiquitin contents detected by western blotting in patient fibroblasts exposed to either pcDNA3.1/empty vector (mock) or pcDNA3.1/PSMC3, as indicated. The y-axis represents the percent changes in densitometry measurements (of pixel intensities using Image J) which are set as 100 % for cells transfected with the pcDNA3.1/empty vector (mock) at 24 post-transfection (n=4, *: p<0.05, t-test). Bars show the mean +/- SEM.",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(C) Patient (index case, IC PSMC3) fibroblasts transfected with either pcDNA3.1/empty vector (mock) or pcDNA3.1/PSMC3 were exposed to a 30-nM treatment of carfilzomib or left untreated (as a negative control). After 16 hours, cells were collected and subjected to RIPA-mediated protein extraction prior to SDS-PAGE and subsequent western-blotting using antibodies specific for ubiquitin, TCF11/Nrf1, Rpt1 (PSMC2), Rpt3 (PSMC4), Rpt5 (PSMC3), Rpt6 (PSMC5), β1, β2, β5, β5i, PA28-α and α-Tubulin (loading control), as indicated. For the TCF11/Nrf1 staining, two exposure times are shown.",
    "ncbi_link": "PSMC3: 5702"
  },
  {
    "caption": "(B-B'). Cataract detection revealed abnormal lens reflection in psmc3 morpholino (MO)-mediated knockdown but not in controls (uninj, ctrl-mo). Similarly, abnormal lens reflection was also observed in embryos injected with sgRNA + Cas9 but not in sgRNA injected embryos without Cas9 (sgRNA2). Co-injection of wt psmc3 mRNA with either psmc3-mo or sgRNA2 + Cas9 reduced the number of embryos presenting abnormal lens reflection. Scale bar = 50 µm. (B') Quantification of embryos with abnormal lens reflection.",
    "ncbi_link": "Cas9: 
psmc3: 5702"
  },
  {
    "caption": "(D-D') bright field images of inner ear development (lateral position). (D) Epithelial projections were fused and formed canal pillars in 4-day-old uninjected and control injected fish (ctrl-mo, sgRNA2) but not in morphants (mo) and crispants (sgRNA2+Cas9). Co-injection of wt psmc3 mRNA with psmc3-mo or sgRNA + Cas9 reduced the number of embryos presenting abnormal ear phenotype. Black asterisks indicate fused pillars. Red arrowheads mark unfused projections. Scale bar = 100 µm. (D') Quantification of embryos with abnormal projection outgrowth.",
    "ncbi_link": "Cas9: 
psmc3: 5702"
  },
  {
    "caption": "(E-E') An anti-acetylated tubulin antibody (green) staining revealed an abnormal amount of kinocilia in psmc3 crispants (sgRNA2+Cas9) compared to uninjected and control injected embryos (sgRNA2). Nuclei are stained in blue with DAPI. Representative images show kinocilia of the lateral cristae. Scale bar = 20 µm. (E') Quantification of embryos with an abnormal amount of kinocilia.",
    "ncbi_link": "Cas9: 
psmc3: 5702"
  },
  {
    "caption": "B: Double-IHC of coronal brain sections (40 μm) of a littermate (LM) and a NexCre cTKO mouse (age: 5 months) stained for Ctip2 (green, expressed in layer V/VI) and Calbindin (red, expressed in layer II/III and to some extent in layer V). Note that no gross abnormalities in cortical lamination were observed. Layers of DAPI stained cell nuclei are denoted on the right (I-VI), scale bar: 100 µm.",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "C: Giemsa-stained, glycolmethacrylate-embedded coronal brain sections (bregma -1.9) displaying the hippocampus and adjacent callosal fiber tracts of a wildtype (WT, top), littermate control (LM, middle) and a NexCre cTKO (cTKO, bottom; age: 5-6 months). Note the agenesis of the corpus callosum (no CC) in NexCre cTKO mice, which should always be present at this bregma and in sections in which the medial habenula (mHb) is present (CC in WT and LM). While WTs and LMs show a compact layer of CA1 cells, NexCre cTKOs display a bilaminar cytoarchitecture (boxed regions marking higher magnification to the right) with scattered ectopic cells in the stratum radiatum (white arrowheads). In addition, the CA3 appears less compact (red arrowheads). Layer identity visualized via Calbindin staining (right panel, scale bar: 50 µm).",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "D: Sholl analysis reveals no genotype effect on basal dendritic segments of deep CA1 pyramidal neurons (dCA1; LM: n=21, N=7; cTKO: n=21/N=6). E: Compared to littermate controls, dCA1 neurons of NexCre cTKO animals show no significant reduction in total dendritic length in basal dendrites (unpaired Student's t-test, nsp = 0.4979). F: The number of primary basal dendrites is significantly reduced in NexCre cTKO animals compared to LM in dCA1 (Mann-Whitney test, **p = 0.0032). G: ",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "A: mEPSC and mIPSC sample traces of recordings from deep CA1 pyramidal cells. B - E: Bar graphs of mEPSC and mIPSC frequencies and amplitudes in deep CA1 pyramidal cells. mEPSC frequency was not different in deep CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (B, p = 0.6415). mEPSC amplitude was increased in deep CA1 pyramidal cells of NexCre cTKO compared to LM control cells (C, *p = 0.0363). mIPSC frequency was not different in deep CA1 pyramidal neurons of adult (4 months) NexCre cTKO versus littermate controls (D, p = 0.0564) and mIPSC amplitude was increased in deep CA1 pyramidal cells of NexCre cTKO compared to LM (E, *p = 0.0356). F: mEPSC and mIPSC sample traces of recordings from superficial CA1 pyramidal cells. G ",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "A: Diurnal behavior in the home cage (HC). NexCre cTKOs show overshooting activity in the dark phase. Line graphs illustrate the average locomotion per hour. [Sidak's multiple comparisons test, geno F(1,32) = 9.503, p = 0.0042; timepoint F(6.102,195.3) = 10.51, p < 0.0001; timepoint × geno F(47,1504) = 5.874, p < 0.0001].",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "I: Sociability in the three chambers test (3CT). LM controls spend more time with mouse stranger 1 (S1) whereas NexCre cTKOs spend comparable time exploring the novel object (NO) or S1. Bottom: schematic representation of test. [Paired Student's t-test comparison between chambers LM ***p = 0.0002; Wilcoxon test between chambers NexCre cTKO ns p = 0.5412].",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "C: T-Maze alternation test shows that spontaneous alternation is absent in NexCre cTKOs. [geno F(1,16) = 18.29, p = 0.0006]. Chance level is indicated by a dotted line.",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "N: Morris Water Maze (MWM), escape latency. During place navigation training, NexCre cTKO animals showed no evidence of learning. [geno F(1,18) = 30.53, p < 0.0001; day F(4,72) = 13.35, p < 0.0001 ; day × geno F(4,72) = 11.77 p < 0.0001].",
    "ncbi_link": "Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "(C) In vitro proteolysis assay. Left, LC3 mutants fused to GST were incubated with HsAtg4B. Right, LC3-GST was incubated with HsAtg4B mutants. Procedures are described in detail in Materials and methods.",
    "ncbi_link": "Atg4B: 23192"
  },
  {
    "caption": "(B) In vitro proteolysis assay using N‐terminal tail‐deleted HsAtg4B. LC3-GST was incubated with either wild‐type or N‐terminally truncated HsAtg4B and was subjected to SDS–PAGE analysis.",
    "ncbi_link": "Atg4B: 23192"
  },
  {
    "caption": "(A) Inducible GFP‐S‐Ubqln1 293 cell line was treated with 1 μg/ml of doxycycline for 24 h. GFP‐S‐Ubqln1 was immunoprecipitated and sent for mass spectrometry analysis. Red sequences indicate Ubqln4 peptides identified by mass spectrometry.",
    "ncbi_link": "Ubqln1: 29979"
  },
  {
    "caption": "(B) 293 cells were co‐transfected with GFP‐S or GFP‐S‐Ubqln1 and HA‐Ubqln4. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐HA antibodies. Lower molecular weight GFP‐tag‐containing bands that appear in the GFP‐S‐Ubqln1 lane might represent degradation products.",
    "ncbi_link": "Ubqln1: 29979"
  },
  {
    "caption": "(D) Confocal images of Hela cells transfected with GFP‐S‐Ubqln1 and RFP‐Ubqln4. Linescan of the white line in the merged image indicates the intensities of the fluorescent molecules in the cross‐section. GFP, green fluorescent protein; HA, haemagglutinin; IP, immunoprecipitation; Ubqln, Ubiquilin; WCL, whole‐cell lysate.",
    "ncbi_link": "Ubqln1: 29979"
  },
  {
    "caption": "Ubqln4 interacts with LC3. Confocal images of (A) Hela cells transfected with GFP‐LC3 and RFP‐Ubqln4 and starved for 1 h or",
    "ncbi_link": "LC3: 440738///81631///84557
Ubqln4: 56893"
  },
  {
    "caption": "(C) 293 cells were transfected with GFP‐S, GFP‐S‐Ubqln1 or GFP‐S‐Ubqln4 and treated with 50 μM chloroquine for 14 h. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐LC3 antibodies.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(E) 293 cells were transfected with GFP‐S‐Ubqln4 WT, GFP‐S‐Ubqln4 ΔSTI1 12, GFP‐S‐Ubqln4 Δ between STI1 or GFP‐S‐Ubqln4 ΔSTI1 34 and treated with 50 μM chloroquine for 14 h. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐LC3 antibodies. GFP, green fluorescent protein; IP, immunoprecipitation; LC3, microtubule‐associated protein light chain 3; Ubqln, Ubiquilin; WCL, whole‐cell lysate; WT, wild‐type.",
    "ncbi_link": "Ubqln4: 56893"
  },
  {
    "caption": "(A) Confocal images of Hela cells transfected with GFP‐S‐Ubqln1 and also transfected with either control or Ubqln4 siRNA. The cells were either untreated or were transferred to starvation medium for 1 h.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(C) Depletion of Ubqln4 with siRNA in (A) was verified by western blot using anti‐Ubqln1, anti‐Ubqln4 and anti‐tubulin antibodies.",
    "ncbi_link": "Ubqln4: 56893"
  },
  {
    "caption": "(D) Hela cells transfected with GFP‐S‐Ubqln1 and also transfected with either control or Ubqln4 siRNA were starved for 1 h. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐LC3 antibodies.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(E) Confocal images of GFP‐S‐Ubqln1 WT in Hela cells transfected with RFP, RFP‐Ubqln4 or RFP‐Ubqln4 ΔUBL.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(F) Quantification of the number of GFP‐S‐Ubqln1 WT puncta per cell in (E). Each bar represents the average and s.e.m. of 30 cells per condition in three independent experiments. *P‐value=0.0001 and **P‐value=0.0003. GFP, green fluorescent protein; IP, immunoprecipitation; LC3, microtubule‐associated protein light chain 3; UBL, ubiquitin‐like; Ubqln, Ubiquilin; WCL, whole‐cell lysate; WT, wild‐type.",
    "ncbi_link": "Ubqln1: 29979"
  },
  {
    "caption": "(A) 293 cells were co‐transfected with GFP‐S‐Ubqln1, GFP‐S‐Ubqln1 ΔUBL (deletion of UBL domain) or GFP‐S‐Ubqln1 ΔUBA (deletion of UBA domain) and HA‐Ubqln4. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐HA antibodies.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(B) The extent of Ubqln4 co‐immunoprecipitation with Ubqln1 was measured and the ratio of Ubqln4 to Ubqln1 was calculated for WT Ubqln1, Ubqln1ΔUBL and Ubqln1ΔUBA. The numbers represent the ratio of Ubqln4 to Ubqln1 relative to WT. Each bar represents the average and s.e.m. of four independent experiments. *P‐value=0.0041.",
    "ncbi_link": "Ubqln1: 29979"
  },
  {
    "caption": "(C) 293 cells were co‐transfected with GFP‐S or GFP‐S‐Ubqln1 and HA‐Ubqln4, HA‐Ubqln4 ΔUBL or HA‐Ubqln4 ΔUBA. GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐HA antibodies.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(D) The extent of Ubqln4 co‐immunoprecipitation with Ubqln1 was measured and the ratio of Ubqln4 to Ubqln1 was calculated for WT Ubqln4, Ubqln4ΔUBL and Ubqln4ΔUBA. The numbers represent the ratio of Ubqln4 to Ubqln1 relative to WT. Each bar represents the average and s.e.m. of four independent experiments. *P‐value=0.0003 and **P‐value=0.0001.",
    "ncbi_link": "Ubqln4: 56893"
  },
  {
    "caption": "(E) 293 cells were co‐transfected with GFP‐S‐Ubqln1 and HA‐Ubqln4, HA‐Ubqln4 ΔUBA or HA‐Ubqln4 ΔUBA I55A (I55 in the UBL domain of Ubqln4 was mutated to A). GFP was immunoprecipitated and analysed by western blot using anti‐GFP and anti‐HA antibodies.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(F) The extent of Ubqln4 co‐immunoprecipitation with Ubqln1 was measured and the ratio of Ubqln4 to Ubqln4 was calculated for WT Ubqln4, Ubqln4ΔUBA and Ubqln4ΔUBA I55A. The numbers represent the ratio of Ubqln4 to Ubqln1 relative to WT. Each bar represents the average of two independent experiments. GFP, green fluorescent protein; HA, haemagglutinin; IP, immunoprecipitation; UBA, ubiquitin‐associated; UBL, ubiquitin‐like; Ubqln, Ubiquilin; WCL, whole‐cell lysate; WT, wild‐type.",
    "ncbi_link": "Ubqln4: 56893"
  },
  {
    "caption": "(A) Confocal images of Hela cells transfected with mCherry‐GFP‐LC3 and also transfected with control, Ubqln1 or Ubqln4 siRNA. The cells were either untreated or were transferred to starvation medium for 8 h.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "(B) Quantification of the number of mCherry/GFP double‐positive and mCherry single‐positive puncta per cell in (A). Each bar represents the average and s.e.m. of 30 cells per condition in three independent experiments. The number of mCherry single‐positive puncta of Ubqln1 and Ubqln4 siRNA was compared with that of control siRNA. *P‐value=0.0475 and **P‐value=0.0373. GFP, green fluorescent protein; LC3, microtubule‐associated protein light chain 3; Ubqln, Ubiquilin.",
    "ncbi_link": "Ubqln1: 29979
Ubqln4: 56893"
  },
  {
    "caption": "Western blot verification of knockout of FASN, ACC1, and/or ACC2 in MDA-MB-231 cells.",
    "ncbi_link": "ACC1: 31
ACC2: 32
FASN: 2194"
  },
  {
    "caption": "Cell proliferation rate of MDA-MB-231 and HeLa cells with knockout of FASN, ACC1, and/or ACC2.",
    "ncbi_link": "ACC1: 31
ACC2: 32
FASN: 2194"
  },
  {
    "caption": "Colony formation ability of MDA-MB-231 cells with knockout of FASN, ACC1, and/or ACC2.",
    "ncbi_link": "ACC1: 31
ACC2: 32
FASN: 2194"
  },
  {
    "caption": "Invasion ability of MDA-MB-231 cells with knockout of FASN, ACC1, and/or ACC2. The right panel shows the pictures of invasive cells, and the cell numbers are quantified in the left panel.",
    "ncbi_link": "ACC1: 31
ACC2: 32
FASN: 2194"
  },
  {
    "caption": "Western blot verification of knockout of KAR or TECR in MDA-MB-231 cells.",
    "ncbi_link": "KAR: 51144
TECR: 9524"
  },
  {
    "caption": "B,C. Cell proliferation rate and colony formation ability of MDA-MB-231 cells with knockout of KAR or TECR. Error bars represent mean ± SD. Data are from triplicate experiments, and all experimental data were verified in at least two independent experiments. **P < 0.01 (t-test); asterisk shows comparison with wild type group.",
    "ncbi_link": "KAR: 51144
TECR: 9524"
  },
  {
    "caption": "Relative cellular levels of fatty acids in MDA-MB-231 cells with knockout of KAR or TECR. Each colored datum shows the mean from three independent cultures.",
    "ncbi_link": "KAR: 51144
TECR: 9524"
  },
  {
    "caption": "G. Relative cellular levels of lipid-containing fatty acids in MDA-MB-231 cells with knockout of KAR or TECR. The top curve plot indicates the fraction of the corresponding fatty acid. Each colored datum shows the mean from three independent cultures.",
    "ncbi_link": "KAR: 51144
TECR: 9524"
  },
  {
    "caption": "H. Mass isotopomer analysis of fatty acids in MDA-MB-231 cells with knockout of KAR or TECR cultured with 10 mM of 13C6-glucose for 48 h. Error bars represent mean ± SD. Data are from three independent cultures.",
    "ncbi_link": "KAR: 51144
TECR: 9524"
  },
  {
    "caption": "The relative cell survival of MDA-MB-231/ACC-DKO or Wt with control vector or Bcl-2 or Bcl-xL overexpression cultured in FBS medium or DFBS medium for 5 days. The left panels show the cell survival, and the right panels verify the overexpression of Bcl-2 and Bcl-xL.",
    "ncbi_link": "Bcl-2: 
Bcl-xL: "
  },
  {
    "caption": "(F-K') (F', G', H', I') are the magnified images of the square region outlined in (F, G, H, I). (F-K) are merged images, (F'-K') are single channel images of (F-K) depicting the presence of NBs (Mira+). Clones (green) are outlined by dotted lines. All images in this figure, and all following figures are single confocal sections. (F-F' and G-G') No Mira+ NBs are recovered in deep sections of control or UAS-dpn clones at 16 hr after clone induction. Quantified in E. (H-H' and I-I') At 24 hr after clone induction, Mira+ NBs are recovered in UAS-dpn but not control clones. Quantified in E. (J-J'and K-K') At 72h after clone induction, numerous Mira+ NBs are recovered in UAS-dpn but not in control clones. Quantified in E.",
    "ncbi_link": "dpn: 35800"
  },
  {
    "caption": "(C-L') Representative images of the deep medulla neuronal layer or NB superficial layer in the larval optic lobe, in which UAS-dpn or control are driven in clones by hs flp (marked by GFP and outlined) and stained with the stem cell marker, Miranda (Mira, magenta), and various temporal transcription factors (tTFs) (grey). (C-G') In superficial sections of control clones, Mira+ superficial NBs express the tTF: Hth, Ey, Slp, D, Tll in concentric patterns. Quantified in M. (H- L') In deep sections of the NB clone induced via UAS-dpn, Mira+ NBs do not express early tTF Hth or late tTF Tll, but are positive for mid tTFs Ey, Slp and D. Quantified in M.",
    "ncbi_link": "GFP: 
dpn: 35800"
  },
  {
    "caption": "(M) Quantification of volume of cells that express a specific tTF as % of total Mira+ NB volume within a clone. Hth (Control n= 5, m= 31.86 ±3.89, UAS-dpn n= 6, m= 7.779 ±1.212), Ey (Control n= 7, m= 26.05 ±5.302, UAS-dpn n= 5, m= 64.08 ±4.936), Slp (Control n= 7, m= 34.87 ±2.753, UAS-dpn n= 9, m= 64.72 ±6.045), D (Control n= 4, m= 34.57 ±15.49, UAS-dpn n= 10, m= 45.2 ±6.339), Tll (Control, n= 5 m= 15.65 ±4.036, UAS-dpn n= 6, m= 3.584, ±1.87).",
    "ncbi_link": "dpn: 35800"
  },
  {
    "caption": "(B) Quantification of % of Slp+ cells in Mira+ cells in control and UAS-dpn clones (expressed as the ratio between Slp+ volume and total Mira+ volume within a clone). 24 hr (Control n= 7, m= 14.25 ±2.696, UAS-dpn n= 9, m= 60.66 ±5.384), 48 hr (Control n= 3, m= 6.096 ±1.509, UAS-dpn n= 8, m= 43.64 ±3.398), 72 hr (Control n= 6, m= 35.13 ±3.242, UAS-dpn n= 9, m= 64.72 ±6.045), 96 hr (Control n= 6, m= 29.85 ±4.951, UAS-dpn n= 10, m= 58.2 ± 6.603).",
    "ncbi_link": "dpn: 35800"
  },
  {
    "caption": "(C-F'') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which UAS-dpn or control are driven by hs flp (marked by GFP and outlined) and dissected and stained with the stem cell marker, Miranda (Mira, magenta), and Sloppy-paired (Slp, grey). At 24h and 48h after clone induction, Mira+ NBs express mid tTF Slp compared to superficial NB control, quantified in B. (C'', D'', E'', F'') are the magnified images of the square region outlined in (C', D', E', F'), respectively.",
    "ncbi_link": "GFP: 
dpn: 35800"
  },
  {
    "caption": "(G-J') At 96h after clone induction, Mira+ NBs express mid tTF Slp and do not express late tTF Tll, compared to control, quantified in B and K. (K) Quantification of % of Tll+ cells in Mira+ cells in control and UAS-dpn clones (expressed as the ratio between Tll+ volume and total Mira+ volume within a clone). Control n= 4, m= 48.34 ±5.956, UAS-dpn n= 5, m= 4.805 ±2.375. D",
    "ncbi_link": "dpn: 35800"
  },
  {
    "caption": "Representative images of the superficial medulla NB layer or deep medulla neuronal layer in the larval or pupal optic lobe, in which UAS-dpn or control (UAS-luciferase) are driven by eyR16F10-GAL4 and stained with the stem cell marker, Miranda (Mira, magenta), (B-E) Mira+ NBs are recovered in superficial sections of control under eyR16F10-GAL4 expression at 6 hr APF and 10 hr APF but not from16 hr APF onwards, quantified in J. (F-I) Mira+ NBs are recovered in deep sections of UAS-dpn driven by eyR16F10-GAL4 at 6 hr APF, 10 hr APF, and 16 hr APF but not at 24 hr APF, quantified in J. Arrow in H points to the NBs. (J) Quantification of % Mira+ cells within eyR16F10-GAL4 expression domain in control and UAS-dpn (calculated as the ratio of Mira+ cell volume as a percentage of total eyR16F10-GAL4 domain volume). 6 hr APF (Control, n= 3, m= 14.82 ±3.521, UAS-dpn, n= 6, m= 18.13 ±1.46), 10 hr APF (Control n= 4, m= 11.65 ±1.605, UAS-dpn n= 5, m= 19.11 ±4.609), 16 hr APF (Control n= 4, m= 0.8897 ±0.239, UAS-dpn n= 7, m= 16.64 ±3.065), 24 hr APF (Control n= 4 m= 1.174, ±0.7226, UAS-dpn n= 6, m= 0.8518 ±0.4849).",
    "ncbi_link": "luciferase: 
dpn: 35800
ey: 43812
GAL4: 855828"
  },
  {
    "caption": "Representative images of the superficial medulla NB layer or deep medulla neuronal layer in the larval or pupal optic lobe, in which UAS-dpn or control (UAS-luciferase) are driven by ok107-GAL4 (outlined) and stained with the stem cell marker, Miranda (Mira, magenta), and mid-temporal progeny marker, Toy-GFP (grey). (K-L') More Toy+ progeny (grey) are present within the ok107-GAL4 domain (green, outlined) in UAS-dpn compared to control.",
    "ncbi_link": "luciferase: 
dpn: 35800
GAL4: 855828"
  },
  {
    "caption": "(O-R') Representative images of the deep medulla neuronal  layer in the larval optic lobe, in which heat shock  induced UAS-dpn or control (UAS-luciferase) clones are stained  with the stem cell marker, Mira  (magenta), late  neuronal marker Tll  (grey) or glial  marker Repo  (grey). Arrow points towards the small band of Tll+ neurons  in control clones. (O-P') At 72 hr after clone induction, there is less Tll expression  within UAS-dpn  clones than control clone, quantified in S. (Q-R') At 72 hr after clone induction, there is less Repo expression  within UAS-dpn clones than control clones, quantified in T.",
    "ncbi_link": "luciferase: 
dpn: 35800"
  },
  {
    "caption": "Representative images of deep medulla neuronal layer in the larval optic lobe, in which UAS-luc; UAS-dpn and UAS-D; UAS-dpn are expressed in clones by hs flp, and stained with the stem cell marker, Miranda (Mira, magenta), and/or Slp, Tll or Repo (grey). (A-B'') At 72 hr after clone induction, Mira+ NBs within UAS-luc; UAS-dpn clones express Slp; Mira+ NBs within UAS-D; UAS-dpn clones do not express Slp, quantified in I. (C-D') Representative images of deep medulla neuronal layer in the larval optic lobe, in which UAS-dpn and UAS-D; UAS-dpn are expressed in the ok107-GAL4 expression domain, and stained with the stem cell marker, Mira (magenta), and mid-temporal progeny marker, Toy-GFP (grey). Fewer Toy+ cells were recovered within the ok107-GAL4 domain (outlined) in UAS-D; UAS-dpn compared to UAS-dpn, quantified in E. (E) Quantification of % Toy+ cells within ok107-GAL4 expression domain in UAS-dpn and UAS-D; UAS-dpn (calculated as the ratio of Toy+ cell volume as a percentage of total ok107-GAL4 domain volume). UAS-dpn n= 9, m= 22.78 ±4.174, UAS-D; UAS-dpn n= 5, m= 14.42 ±2.394.",
    "ncbi_link": "luc: 
dpn: 35800
GAL4: 855828"
  },
  {
    "caption": "(J-K) Quantification of % Tll+ or Repo+ cells within UAS-dpn clones compared to UAS-D; UAS-dpn clones (calculated as the ratio of Tll+ or Repo+ cell volume as a percentage of total clone volume). Tll (UAS-dpn n= 7, m= 0.7198 ±0.2389, UAS-D; UAS-dpn n= 9, m= 35.22 ±4.917), Repo (UAS-dpn n= 7 m= 1.488 ±0.2368, UAS-D; UAS-dpn n= 9, m= 14.13 ±2.672).",
    "ncbi_link": "dpn: 35800"
  },
  {
    "caption": "(L-M) Mira+ NBs are present in deep sections of UAS-dpn driven by eyR16F10-GAL4 at 126h but are absent in UAS-D; UAS-dpn, quantified in N. (N) Quantification of % Mira cells within eyR16F10-GAL4 expression domain in UAS-dpn and UAS-D; UAS-dpn (calculated as the ratio of Mira+ cell volume as a percentage of total eyR16F10-GAL4 domain volume). UAS-dpn n= 6, m= 18.13 ±1.46, UAS-D; UAS-dpn n= 8, m= 1.859 ±0.4215. D",
    "ncbi_link": "dpn: 35800
ey: 43812
GAL4: 855828"
  },
  {
    "caption": "(A-C'') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which control (UAS-luc) and UAS-dpn and UAS-D; UAS-dpn are expressed in hs flp clones (72 hr after clone induction). Miranda (Mira, magenta) and EdU (grey). Despite increased number of Mira+ cells in UAS-dpn compared to control, each NB underwent slower cell cycle progression, as indicated by EdU+ incorporation. Quantified in E. This slow cell cycle speed was not rescued in UAS-D; UAS-dpn clones. Quantified with UAS-luc; UAS-dpn in F.",
    "ncbi_link": "luc: 
dpn: 35800"
  },
  {
    "caption": "(G-H''') Representative images of the deep medulla neuronal layer in the larval optic lobe, where UAS- E2f1; UAS- CycE; UAS-dpn or UAS-dpn are expressed in the ok107-GAL4 domain (outlined), and stained with the stem cell marker, Mira (magenta), mid-tTF, Slp (grey) and late progeny marker, Repo (Cyan). Quantified in I-K. UAS-dpn NBs express Slp and do not create Repo+ progeny, whereas UAS- E2f1; UAS- CycE; UAS-dpn NBs do not express Slp and create Repo+ progeny.",
    "ncbi_link": "CycE: 34924
dpn: 35800
E2f1: 42550
GAL4: 855828"
  },
  {
    "caption": "(B-D''') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which control (UAS-luc), UAS-NACT, and UAS-D; UAS-NACT are driven by eyR16F10-GAL4 (outlined). Miranda (Mira, magenta), Sloppy paired (Slp, grey), Tailless (Tll, cyan). UAS-NACT NBs express Slp and not Tll. UAS-D; UAS-NACT NBs express Slp and Tll, quantified in E-H.",
    "ncbi_link": "luc: 
ey: 43812
GAL4: 855828"
  },
  {
    "caption": "(J-K') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which UAS-NACT and UAS-NACT; UAS-dpn are driven by ok107-GAL4 (marked by GFP and outlined) and stained with the stem cell marker, Mira (magenta), and mid-temporal progeny marker, Toy-GFP (grey). Fewer cells express Toy+ in UAS-NACT; UAS-dpn compared to UAS-NACT, quantified in I.",
    "ncbi_link": "GFP: 
dpn: 35800
GAL4: 855828"
  },
  {
    "caption": "(A-C''') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which control (UAS-lacz), lola-Ri, and UAS-D; lola-Ri are driven by eyR16F10-GAL4 (outlined). Miranda (Mira, magenta), Sloppy-paired (Slp, grey), Twin of eyeless (Toy, cyan). lola-Ri induces ectopic Mira+ NBs in the deep medulla layers, compared to control, quantified in E.",
    "ncbi_link": "ey: 43812
GAL4: 855828
lacz: 945006
lola: 44548"
  },
  {
    "caption": "(H-J''') Representative images of the deep medulla neuronal layer in the larval optic lobe, in which control (UAS-lacz), lola-Ri, and UAS-D; lola-Ri are driven by eyR16F10-GAL4 (outlined). Miranda (Mira, magenta), Tailless (Tll, grey), Reversed polarity (Repo, cyan). lola-Ri NBs express less Tll compared to control. There are fewer Tll+ and Repo+ progeny in the eyR16F10-GAL4 domain in lola-Ri compared to control. UAS-D; lola-Ri NBs express more Tll as well as more Tll+ and Repo+ progeny in eyR16F10-GAL4 domain compared to lola-Ri alone, quantified in K-L.",
    "ncbi_link": "ey: 43812
GAL4: 855828
lacz: 945006
lola: 44548"
  },
  {
    "caption": "Images of representative individuals (F) of 4-day-old seedlings grown with or without supplemental UV-B. The scale bar for all lines represent 5 mm except for cop1-5 where the scale bars represent 1 mm. Data Information , lines used: wild-type (Ws), uvr8-7, cop1-4, cop1-5/Pro35S:YFP-COP1 (WT), cop1-5/Pro35S:YFP-COP1Lys422Ala, cop1-5/Pro35S:YFP-COP1Tyr441Ala, cop1-5/Pro35S:YFP-COP1Trp467Ala and cop1-5. #1 and #2: independent transgenic lines.",
    "ncbi_link": "YFP: 
cop1-5: 817857
COP1: 817857
cop1-4: 817857
uvr8: 836506"
  },
  {
    "caption": "quantification of hypocotyl lengths (G) of 4-day-old seedlings grown with or without supplemental UV-B. The scale bar for all lines represent 5 mm except for cop1-5 where the scale bars represent 1 mm. Violin and box plots are shown for n > 60 seedlings; upper and lower hinges correspond to the first and third quartiles, the horizontal line in the interior of the box indicates the median. Data Information: lines used: wild-type (Ws), uvr8-7, cop1-4, cop1-5/Pro35S:YFP-COP1 (WT), cop1-5/Pro35S:YFP-COP1Lys422Ala, cop1-5/Pro35S:YFP-COP1Tyr441Ala, cop1-5/Pro35S:YFP-COP1Trp467Ala and cop1-5. #1 and #2: independent transgenic lines.",
    "ncbi_link": "YFP: 
cop1-5: 817857
COP1: 817857
cop1-4: 817857
uvr8: 836506"
  },
  {
    "caption": "Quantitative real-time PCR analysis of (H) HY5 expression. Four-day-old seedlings grown in white light were exposed to narrowband UV-B for 2 hours (+UV-B), or not (-UV-B). Error bars represent SEM of 3 biological replicates. Data Information: lines used: wild-type (Ws), uvr8-7, cop1-4, cop1-5/Pro35S:YFP-COP1 (WT), cop1-5/Pro35S:YFP-COP1Lys422Ala, cop1-5/Pro35S:YFP-COP1Tyr441Ala, cop1-5/Pro35S:YFP-COP1Trp467Ala and cop1-5. #1 and #2: independent transgenic lines.",
    "ncbi_link": "YFP: 
cop1-4: 817857
cop1-5: 817857
COP1: 817857
HY5: 830996
uvr8: 836506"
  },
  {
    "caption": "Quantitative real-time PCR analysis of (I) RUP2 expression. Four-day-old seedlings grown in white light were exposed to narrowband UV-B for 2 hours (+UV-B), or not (-UV-B). Error bars represent SEM of 3 biological replicates. Data Information lines used: wild-type (Ws), uvr8-7, cop1-4, cop1-5/Pro35S:YFP-COP1 (WT), cop1-5/Pro35S:YFP-COP1Lys422Ala, cop1-5/Pro35S:YFP-COP1Tyr441Ala, cop1-5/Pro35S:YFP-COP1Trp467Ala and cop1-5. #1 and #2: independent transgenic lines.",
    "ncbi_link": "YFP: 
COP1: 817857
cop1-4: 817857
cop1-5: 817857
RUP2: 832438
uvr8: 836506"
  },
  {
    "caption": "F. Yeast 3-hybrid analysis of the COP1 - HY5 interaction in the presence of UVR8. (Top) Normalized Miller Units were calculated as a ratio of β-galactosidase activity in yeast grown under UV-B (+ UV-B) versus yeast grown without UV-B (- UV-B). Additionally, normalized Miller Units are reported separately here for yeast grown on media without or with 1 mM methionine, corresponding to induction (- Met) or repression (+ Met) of Met25 promoter-driven UVR8 expression, respectively. Means and SEM for 3 biological repetitions are shown. (Bottom) representative filter lift assays. AD, activation domain; BD, DNA binding domain; Met, methionine.",
    "ncbi_link": "UVR8: 836506"
  },
  {
    "caption": "B. Representative image showing the phenotype of wild-type (Ws), uvr8-7 and uvr8-7/Pro35S:UVR8HY5C44, uvr8-7/Pro35S:UVR8HY5VP and uvr8-7/Pro35S:UVR8TRIB1 seedlings grown for 4 days under white light (- UV-B) or white light supplemented with UV-B (+ UV-B). The scale bar represents 5 mm.",
    "ncbi_link": "TRIB1: 10221
uvr8: 836506
UVR8: 836506"
  },
  {
    "caption": "E. Quantitative real-time PCR analysis of RUP2, CHS, HY5 and ELIP2 expression in wild-type (Ws), uvr8-7 and uvr8-7/Pro35S:UVR8HY5C44, uvr8-7/Pro35S:UVR8HY5VP and uvr8-7/Pro35S:UVR8TRIB1 4-day old seedlings grown under white light in response to 2h of UV-B (+UV-B vs. -UV-B). Error bars represent SEM of 3 biological replicates. Note: the primers used to detect the HY5 transcript abundance also bind to an identical region present in UVR8HY5C44 chimera.",
    "ncbi_link": "ELIP2: 827119
HY5: 830996
RUP2: 832438
TRIB1: 10221
CHS: 831241
uvr8: 836506
UVR8: 836506"
  },
  {
    "caption": "F. Yeast 3-hybrid analysis of the COP1-HY5 interaction in the presence of the UVR8HY5C44 chimera. (Left pane) Normalized Miller Units were calculated as a ratio of β-galactosidase activity in yeast grown under UV-B (+ UV-B) versus yeast grown without UV-B (- UV-B). Additionally, normalized Miller Units are reported separately here for yeast grown on media without or with 1 mM methionine, corresponding to induction (- Met) or repression (+ Met) of Met25 promoter-driven UVR8 expression, respectively. Means and SEM for 3 biological repetitions are shown. (Right panel) Representative filter lift assays of the yeast analyzed in left panel. AD, activation domain; BD, DNA binding domain; Met, methionine.",
    "ncbi_link": "UVR8: 836506"
  },
  {
    "caption": "A. Representative image of wild-type (Ws), cop1-5/Pro35S:YFP-COP1, cop1-5/Pro35S:YFP-COP1Lys422Ala, cop1-5/Pro35S:YFP-COP1Tyr441Ala and cop1-5/Pro35S:YFP-COP1Trp467Ala transgenic lines grown for 39 days in long day conditions.",
    "ncbi_link": "YFP: 
cop1-5: 817857
COP1: 817857"
  },
  {
    "caption": "B. Representative image of individual wild-type (Ws), co-11, cop1-5/Pro35S:YFP-COP1 and cop1-5/Pro35S:YFP-COP1Lys422Ala plants grown for 39 days in long days conditions.",
    "ncbi_link": "YFP: 
co: 831441
COP1: 817857
cop1-5: 817857"
  },
  {
    "caption": "E. Immunoblot analysis of CRY2 and actin (loading control) protein levels in wild-type (Col), cry2-1, wild-type (Ws), cop1-5/Pro35S:YFP-COP1 and cop1-5/Pro35S:YFP-COP1Lys422Ala seedlings grown for 4 days in darkness.",
    "ncbi_link": "YFP: 
COP1: 817857
cop1-5: 817857
cry2-1: 839529"
  },
  {
    "caption": "E Representative fluorescent stereo-micrographs of glands injected with MM134:RFP-luc2  cells (left, top and bottom) infected with either GFP:sh-scramble (top) or GFP+ shLOXL1  (bottom), n=5 and 3. Scale bar, 1000 μm. F Barplot showing the ratio of GFP/RFP signal from fluorescent stereo-micrographs  of glands engrafted with MM134  cells, n=8. Statistical analysis by paired Student t-test, two-tailed. *p < 0.05. ",
    "ncbi_link": "GFP: 
luc2: 
RFP: 
LOXL1: 4016"
  },
  {
    "caption": "H Representative  fluorescent stereo-micrographs  of glands engrafted with SUM44:RFPluc2 cells infected with either GFP:sh-scramble (top) or GFP+ shLOXL1, n=6. Scale bar, 1000 μm. I Barplot (mean ± SEM) showing quantification of the ratio GFP/RFP  from fluorescent stereo-micrographs of SUM44. Statistical analysis by unpaired Student's t-test, two-tailed, n=7 sh-scramble and n=6 for sh-LOXL1, ****p < 0.0001. ",
    "ncbi_link": "GFP: 
luc2: 
RFP: 
LOXL1: 4016"
  },
  {
    "caption": "J, K Representative photomicrographs of picrosirius red stained  histological sections for sh-scramble or sh-LOXL1 MM134 (J) and SUM44 (K) xenografts. Scale bars, 100 μm.",
    "ncbi_link": "LOXL1: 4016"
  },
  {
    "caption": "(K) HEK-293T cells were transfected with Flag-NLRP3 or Flag-vector and then treated with LicoB (40 μM). Immunoprecipitation was performed with anti-DYKDDDDK (Flag) affinity gel agarose beads; Western blot analysis has been shown.",
    "ncbi_link": "Flag: 
NLRP3: "
  },
  {
    "caption": "Under the same growth conditions (permitted water, free food, and a 12 h/12 h dark/light cycle at 20±2°C), eight-week-old male C57BL/6 mice were continuously fed with methionine- and choline-supplemented (MCS) or methionine- and choline-deficient (MCD) diets for 6 weeks, and at the same time, gavaged with LicoB, MCC950 n=6 mice per group Real-time quantitative PCR was used to detect the mRNA levels of Col1a1 (E), TNF-α (F) in the mice livers, as described in (A) (n=6 mice per group).",
    "ncbi_link": "Col1a1: 12842
TNF-α: 21926"
  },
  {
    "caption": "Under the same growth conditions (permitted water, free food, and a 12 h/12 h dark/light cycle at 20±2°C), eight-week-old male C57BL/6 mice were continuously fed with methionine- and choline-supplemented (MCS) or methionine- and choline-deficient (MCD) diets for 6 weeks, and at the same time, gavaged with LicoB, MCC950 n=6 mice per group Real-time quantitative PCR was used to detect the mRNA levels of IL-1β (G), and IL-18 (H) in the mice livers, as described in (A) (n=6 mice per group).",
    "ncbi_link": "IL-18: 16173
IL-1β: 16176"
  },
  {
    "caption": "A-C qPCR of selected transcripts at day 31 to validate (A) enrichment of cardiac markers in GFP+ fractions against GFP− fractions, (B) upregulation of atrial and (C) downregulation of ventricular genes in RA+ compared to CT+ (n = 3).Data information: Data are presented as mean ± SEM. In (A-C), *P < 0.05, **P < 0.01, ***P < 0.001 by unpaired t-test. In (A), for TNNT2, P = 0.0001 for CT− against CT+ and P = 0.0002 for RA− against RA+; for NKX2.5, P = 0.00005 for CT− against CT+ and P = 0.00007 for RA− against RA+. In (B), P = 0.0006 for NPPA and P = 0.0002 for PITX2. In (C), P = 0.02 for HEY2 and P = 0.007 for IRX4.",
    "ncbi_link": "HEY2: 23493
IRX4: 50805
NKX2.5: 1482
NPPA: 4878
PITX2: 5308
TNNT2: 7139"
  },
  {
    "caption": "A, B Line plot illustrating relative mRNA levels of (A) COUP-TFI and (B) COUP-TFII in VM and AM differentiations from day 5 through day 9 (left) and in GFP+CMs at day 31 (right); n = 3.Data information: Data are presented as mean ± SEM. In (A, B), *P < 0.05, **P < 0.01, ***P < 0.001 by unpaired t-test. In (A), left panel, P = 0.03, 0.02, 0.03, 0.005 and 0.0004 for comparison of COUP-TFI expression between AM and VM at days 5, 6, 7, 8 and 9 of differentiation. In (A), right panel, P = 0.0002 for comparison of COUP-TFI expression at day 31 between AM and VM. In (B), left panel, P = 0.02, 0.03, 0.006, 0.004 and 0.003 for comparison of COUP-TFII expression between AM and VM at days 5, 6, 7, 8 and 9 of differentiation. In (B), right panel, P = 0.0001 for comparison of COUP-TFII expression at day 31 between AM and VM. CT = control differentiation; hESC-atrial (AM); hESC-ventricular (VM).",
    "ncbi_link": "COUP-TFI: 7025
COUP-TFII: 7026"
  },
  {
    "caption": "A, B mRNA expression of COUP-TFI and COUP-TFII following shRNA-mediated knockdown of (A) COUP-TFI or (B) COUP-TFII in hESC-atrial cardiomyocytes (AM) at day 30.",
    "ncbi_link": "COUP-TFI: 7025
COUP-TFII: 7026"
  },
  {
    "caption": "C, D mRNA expression of ion channel genes KCNA5, KCNJ3 and KCNJ5 after knockdown of (C) COUP-TFI or (D) COUP-TFII in AM at day 30.",
    "ncbi_link": "KCNA5: 3741
KCNJ3: 3760
KCNJ5: 3762
COUP-TFI: 7025
COUP-TFII: 7026"
  },
  {
    "caption": "E, F Schematic of NR2F binding sites in (E) KCNA5 and (F) KCNJ3 promoters.G, H ChIP-qPCR analysis at day 30 shows enriched binding of COUP-TFI and COUP-TFII to the promoter region of (G) KCNA5 and (H) KCNJ3, compared to IgG in AM.",
    "ncbi_link": "KCNA5: 3741
KCNJ3: 3760"
  },
  {
    "caption": "A Expression of KCNA5 (left) and KCNJ3 (right) in GFP+ pools of VM and AM CMs at day 31, as well as in ventricles and atria of human heart.",
    "ncbi_link": "KCNA5: 3741
KCNJ3: 3760"
  },
  {
    "caption": "D. Log-normalized expression  z-score of genes up- (top panels) and downregulated (bottom panels) by Ascl1   (left, blue violins) and MyoD1   (right, yellow violins) versus their scaled expression  levels (x-axis) binned into 10% intervals. For each box, the centerline defines the median, the height of the box is given by the interquartile range (IQR), the whiskers are given by 1.5 * IQR and outliers are given as points beyond the minimum or maximum whisker.",
    "ncbi_link": "Ascl1: 17172
MyoD1: 17927"
  },
  {
    "caption": "F. Representative immunofluorescence  images of cells 3 days after transgene induction. Cells were stained  for the fluorescent reporter present on the PiggyBac construct of the reprogramming factor. Arrows indicate  multinucleated cells. Scale bar represents 50 µm. mutAscl1 = mutant Ascl1. G. Quantification of the percentage of cells with more than one nucleus  among all transfected cells within a given condition. Data points represent biological replicates (n = 4). For each box, the centerline defines the median, the height of the box is given by the interquartile range (IQR), the whiskers are given by 1.5 * IQR and outliers are given as points beyond the minimum or maximum whisker. Pairwise comparisons performed with Mann-Whitney U test, correction for multiple testing performed with Benjamini-Hochberg correction. *: p < 0.05 (MyoD1     vs Ascl1: p = 0.03, MyoD1     vs mutAscl1: p = 0.03, MyoD1     vs Ascl1     & MyoD1: p = 0.03, MyoD1     vs mutAscl1 & MyoD1: p = 0.03, Ascl1     vs Ascl1     & MyoD1: p = 0.03, Ascl1     vs mutAscl1  & MyoD1: p = 0.03, mutAscl1   vs Ascl1    & MyoD1: p = 0.03, mutAscl1  vs mutAscl1   & MyoD1: p = 0.03",
    "ncbi_link": "Ascl1: 17172
MyoD1: 17927"
  },
  {
    "caption": "(B-C) The phospholipases pla2g4aa  and pla2g4ab  are highly expressed  in neutrophils. Data information: For each panel, data represents biological triplicates plated in technical duplicates. Statistical analysis was completed using one-way ANOVA, multiple comparison test. * P<.05; **P<.01; ***P<.001; ****P<.0001. Center values denote the mean, and error bars denote s.e.m.",
    "ncbi_link": "pla2g4aa: 30554
pla2g4ab: 559087"
  },
  {
    "caption": "(D-E-F) The expression  of cyclooxygenases cox1, cox2a  and cox2b  is enriched in macrophages. (G-H) The prostaglandin synthases ptges3a  and ptges3b  are only expressed  by ECs. (I-O) The prostaglandin receptors ptger1a, ptger1b, ptger2a, ptger3, ptger4a  are mostly expressed  in HSPCs. (P-Q) The prostaglandin transporters slco2b1  and abcc4  are specifically expressed  in ECs. Data information: For each panel, data represents biological triplicates plated in technical duplicates. Statistical analysis was completed using one-way ANOVA, multiple comparison test. * P<.05; **P<.01; ***P<.001; ****P<.0001. Center values denote the mean, and error bars denote s.e.m.",
    "ncbi_link": "abcc4: 368620
cox1: 140539
ptger1a: 559315
ptger1b: 564945
ptger2a: 393608
ptger3: 100000544
ptger4a: 562469
ptges3a: 406449
ptges3b: 415227
cox2a: 246227
cox2b: 559020
slco2b1: 792084"
  },
  {
    "caption": "(A) Schematic indicating the imaging area in the tail  at 72hpf, as indicated by the black box; fluorescence imaging of the CHT  in double transgenic cd45:CFP-NTR/runx1:mcherry embryos  in DMSO  and after treatment with MTZ  and PGH2  or PGE2. (B) Quantification of runx1:mcherry  positive-cells (C) Quantification of cd45:CFP  positive-cells in double transgenic cd45:CFP-NTR/runx1:mcherry embryos  in DMSO  and after treatment with MTZ  and PGH2 or PGE2. Data information: Statistical analysis was completed using one-way ANOVA, multiple comparison test. * P<.05; **P<.01; ***P<.001 ****P<.0001. Scale bar 200μm (A).",
    "ncbi_link": "mcherry: 
CFP: 
NTR: 945778
cd45: 559154
runx1: 12394"
  },
  {
    "caption": "(A) WISH for cmyb expression  at 60hpf in wild type and slco2b1-/- embryos. (B) Quantification of cmyb-expressing cells. Each n represents the number of cmyb-expressing cells for each embryo  (biological replicates). Each experiment has been repeated three independent times. Data information: Centre values denote the mean, and error values denote s.e.m. The statistical analysis was completed using an unpaired two tailed t test. ***P < .001 Scale bar 500μm (A)",
    "ncbi_link": "cmyb: 30519
slco2b1: 792084"
  },
  {
    "caption": "(C) Schematic indicating the imaging area in the tail  at 60hpf, as indicated by the black box; fluorescence imaging in the CHT  of kdrl:mCherry;cmyb:GFP embryos  injected with control- and slco2b1-Mos. (D) Quantification of HSPCs  associated to ECs. Each n represents the number of yellow spots for each embryo  (biological replicates). Each experiment has been repeated three independent times. Data information: Centre values denote the mean, and error values denote s.e.m. The statistical analysis was completed using an unpaired two tailed t test. ***P < .001 Scale bar 200μm (C)",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(E) Experimental outline and quantification of time-lapse live imaging  in controls and slco2b1-morphants  cmyb:GFP+ cells, using Imaris software. Data information: The statistical analysis was completed using an unpaired two tailed t test. ***P < .001",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(A) Anti-GFP  and pH3 immunostainings  of either controls (Ctrl-Mo) or slco2b1-morphants (slco2b1-MO) cmyb:GFP embryos. (B) Quantification of the number of the pH3+ HSCs  in controls or slco2b1-morphants. Centre values denote the mean, and error values denote s.e.m, statistical analysis was completed using an unpaired two tailed t test. ***P < .001. Data information: Scale bar 50μm (A)",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(D) Quantification of PGE2   concentration in control and slco2b1   morphants. The statistical analysis was completed using an unpaired two tailed t test *P < .01. Centre values denote the mean, and error bars denote s.e.m.",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(E) Fluorescence imaging in the CHT  of cmyb:GFP embryos  injected with control- and slco2b1-MOs  and treated with PGE2. (F) Quantification of GFP  positive cells. Statistical analysis: one-way ANOVA, multiple comparison, *P < .01; ****P < .0001. Centre values denote the mean, and error bars denote s.e.m. Data information: Scale bar 200μm (E).",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(A) Fluorescence imaging of the CHT  of double transgenic cd45:CFP-NTR/runx1:mcherry embryos  injected with control- or slco2b1-morpholinos, after treatment with DMSO. (B) Fluorescence imaging of the CHT  of double transgenic cd45:CFP-NTR/runx1:mcherry embryos  injected with control- or slco2b1-morpholinos, after treatment with DMSO+MTZ. (C) Fluorescence imaging of the CHT  of double transgenic cd45:CFP-NTR/runx1:mcherry embryos  injected with control- or slco2b1-morpholinos, after treatment with DMSO+MTZ+PGH2. (D) Quantification of runx1:mcherry  positive-cells. Each dot represents the number of red cells for each embryo  (biological replicates). Each experiment has been repeated three independent times. (E) Quantification of cd45:CFP  positive-cells. Each dot represents the number of blue cells for each embryo  (biological replicates). Each experiment has been repeated three independent times.Data information for (D) and (E): Statistical analysis was completed using one-way ANOVA, multiple comparison test. ****P<.0001. Centre values denote the mean, and error bars denote s.e.m Scale bar 200μm (A-C).",
    "ncbi_link": "slco2b1: 792084"
  },
  {
    "caption": "(A) WISH  for cmyb  at 60hpf in  kdrl:Gal4+ embryos  injected with control- and slco2b1- morpholinos  and/or co-injected with the Tol2-UAS:slco2b1 vector and tol2  mRNA. The region indicated by the dashed bas been magnified and shows in (B). (C) Quantification and statistical analysis were completed using one-way ANOVA, multiple comparison test. ****P< .0001. Centre values denote the mean, and error bars denote s.e.m. Each dot represents the number of cmyb-expressing cells for each embryo  (biological replicates). Each experiment has been repeat three independent times.",
    "ncbi_link": "tol2: 
Tol2: 
cmyb: 30519
slco2b1: 792084"
  },
  {
    "caption": "Automated microinjection was performed on organotypic slices of mouse E14.5 dorsal telencephalon using Dx-A488 along with mRNA for RFP Organotypic slices of mouse E14.5 dorsal telencephalon injected with Dextran-A488 (green) and RFP poly-A+-mRNA. After 24h in culture the progeny expresses RFP (magenta; blue: DAPI, n = 17 cells injected, 8 RFP positive). Percentage of RFP-positive and RFP-negative cells (n = 17 cells injected).",
    "ncbi_link": "RFP: "
  },
  {
    "caption": "(F) qRT-PCR validation of Irf7 and Irf9 downregulation in RM1 cells from bone metastases (RMI BD) compared to parental RM1 cells, lung metastases (RM1 lung) and naïve bone marrow (BM) (n = 3 mice per group). p values represented as ** < 0.005 and *** < 0.0005 (Student's t test).",
    "ncbi_link": "Irf7: 54123
Irf9: 16391"
  },
  {
    "caption": "(G) qRT-PCR of Irf7 and Irf9 downregulation in parental RM1 cells, RM1 cells from bone metastases (RM1 BD) in WT and Ifnar1 deficient (-/-) mice, with naïve BM from WT and Ifnar1 (-/-) animals for reference. (n = 3 mice per group; n = 1 for -/- BM control). p values represented as * < 0.05 and ** < 0.005 (Student's t test).",
    "ncbi_link": "Ifnar1: 15975
Irf7: 54123
Irf9: 16391"
  },
  {
    "caption": "(A) Stability of Irf7 and Irf9 mRNA suppression by qRT-PCR in ex vivo bone-derived cells (RM1 BD Irf-; n = 7) in culture compared to a bone-derived line that showed initial loss during early passage (RM1 BD REV (EP); n = 3) then reverted to parental expression levels at late passage (RM1 BD REV (LP); n = 4) compared to parental RM1 (n = 3).",
    "ncbi_link": "Irf7: 54123
Irf9: 16391"
  },
  {
    "caption": "(C) qRT-PCR analysis of Irf7 and Irf9 expression in RM1 BD Irf- cells ± 48 h treatment with MS275 (1 μM) (n = 7-9).",
    "ncbi_link": "Irf7: 54123
Irf9: 16391"
  },
  {
    "caption": "(e) qRT-PCR analysis of Irf7 and Irf9 expression in parental RM1 cells (n = 4) 48 h post-contact culture with naïve BM (n = 6).",
    "ncbi_link": "Irf7: 54123
Irf9: 16391"
  },
  {
    "caption": "(F) qRT-PCR analysis of Irf9 expression in parental RM1 cells ± 48 h co-culture with naïve BM under contact (non-transwell; NT) and transwell (0.4 μm filters that prevent cell contact) conditions (n = 6-8 per condition).",
    "ncbi_link": "Irf9: 16391"
  },
  {
    "caption": "(G) qRT-PCR analysis of Irf9 expression in parental RM1 cells ± 48 h contact co-culture with naïve BM ± MS275 (1 μM) (n = 3-6 per condition).",
    "ncbi_link": "Irf9: 16391"
  },
  {
    "caption": "(C) ELISA of IFN-α production by RM1 parental, RM1 BD Irf- base vector (BV) and RM1 BD Irf7 over-expressing (OE) with 24 h poly I:C stimulation (n = 4).",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(D) Bone metastasis-free survival in WT C57BL/6 mice subsequent to IC inoculation of RM1 BD Irf- BV (n = 9) and RM1 BD Irf7 OE (n = 7) cells (**p = 0.0028 by log-rank (Mantel-Cox) test).",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(E) Bone metastasis-free survival in Ifnar1 -/- mice harboring RM1 BD Irf- BV and RM1 BD Irf7 OE tumors (n = 4 per group) and representative bioluminescent imaging of tumor burden in leg bones (also shown in Appendix Fig S4F).",
    "ncbi_link": "Ifnar1: 15975
Irf7: 54123"
  },
  {
    "caption": "(F) Immunohistochemical (IHC) staining for cerulean (anti-eCFP; green) on naïve WT bone, RM1 parental, RM1 BD Irf- BV and RM1 BD Irf7 OE tumor-bearing bones derived from WT animals; and RM1 BD Irf7 OE tumor-bearing bones derived from Ifnar1 -/- animals at survival assay endpoints. Blue represents DAPI nuclear staining. Scale bar, 100 μm.",
    "ncbi_link": "Ifnar1: 15975
Irf7: 54123"
  },
  {
    "caption": "(G-I) FACS analysis of dormant (claret+) RM1 BD Irf- and RM1 BD Irf7 OE cells from bone at (G) day 11 post-IC injection (n = 4 per group) and (h) day 17 (n = 4-6 mice group/time point) with (I) D17 active (claret-) colony quantitation (mean +1) determined by multiphoton imaging and IMARIS interrogation (n = 9 bones from 3 mice per condition). Median shown. Upper and low box hinges denote first and third quartiles. Whiskers mark value limits.",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(J) FACS analysis of IFN-γ+ and TNF-α+ CD8+ T cells (%) post-ICS induction of T cell (spleen-derived from tumor-bearing mice) activation by RM1 parental, RM1 BD Irf- BV and RM1 BD Irf7 OE cells (n = 6 per condition/group).",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(K) Mean quantitation of TRAP-stained osteoclasts differentiated with M-CSF ± RANKL in co-culture with RM1 BD Irf- BV and RM1 BD Irf7 OE cells with representative wells shown (n = 3 per condition M-CSF; n = 6 per condition M-CSF + RANKL; also shown in Appendix Fig S4J). Scale bar represents 100 μm.",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(C) FACS analysis of IFN-γ+ CD8+ T cells (%) post-ICS induction of T cell (spleen-derived from RM1 BD Irf- tumor-bearing mice) activation upon re-stimulation with RM1 cells and MS275, poly I:C or combination treatment, with NAC (no antigen-presenting cells) and RM1 BD Irf7 OE controls (n = 3; Irf7 OE control (C), n = 1)",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "FACS analysis of IFN-γ+ CD8+ T cells (%) post-ICS induction of T cell (spleen-derived from RM1 BD Irf- tumor-bearing mice) activation upon re-stimulation with RM1 cells and MS275, poly I:C or combination treatment, with NAC (no antigen-presenting cells) and RM1 BD Irf7 OE controls (n = 3; Irf7 OE control (C), n = 1) with (D) representative FACS plots shown.",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "D) post-IC inoculation with associated specific CD8+ memory T cell response. This is represented by FACS analysis of IFN-γ+ CD8+ T cells (%) post-ICS induction of T cell (spleen-derived from tumor-bearing mice) activation upon re-stimulation with RM1 BD Irf- cells and MS275, poly I:C or combination treatments in vitro, with NAC and RM1 BD Irf7 OE controls (n = 3; Irf7 OE control (C), n = 1). Representative FACS plots shown on right.",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "(C). The table summarises the number and the sex of the embryos of the indicated genotypes, recovered from timed matings of Rif1+/- x Rif1+/- mice, in a C57BL/6J genetic background. The day of gestation (E) is indicated.",
    "ncbi_link": "Rif1: 51869"
  },
  {
    "caption": "(C). Time course analysis of Xist RNA expression by RT-qPCR during EB differentiation of Rif1+/+ (Rif1+/+ +OHT) and Rif1-/- (Rif1F/F +OHT) cells at the indicated timepoints. Rif1+/+ (solid line) and Rif1-/- (dashed line), female (black) and male (grey). Data are presented as mean ± standard deviation from three (female lines) or two (male lines) independent experiments. Statistical significance was determined using 2-way ANOVA comparing female Rif1+/+ to female Rif1-/- cell lines (****p ≤ 0.0001). Xist RT-primers Xist ex7 F and R were used. Values are normalised to a geometric mean consisting of the expression of Gapdh, Ubiquitin and β-Actin.",
    "ncbi_link": "β-Actin: 11461
Gapdh: 14433
Rif1: 51869
Xist: 213742"
  },
  {
    "caption": "RIF1 association with the Xist promoter assessed by ChIP-qPCR in two independent Rif1+/+ (Rif1+/+ +OHT, black) and two Rif1-/- (Rif1F/F +OHT, grey) female cell lines, in ESCs (A) P1 and P2 indicate the two Xist promoters, 5' indicates a region 2 kb upstream of Xist TSS. Inter1 and 2 are two intergenic regions that serve as negative controls. Peak and cRAD represent two previously identified regions of RIF1 association (positive control). See Appendix Fig. S2C for primer positions within Xist. Mean ±standard deviation from 3 independent experiments (A) and 2 independent experiments (B). p calculated by Student's two-tailed, paired t test comparing RIF1 association in Rif1+/+ cells on Xist P2 and P1 versus 5'. *p ≤ 0.05, ****p ≤ 0.0001 and ns=not significant.",
    "ncbi_link": "Rif1: 51869
Xist: 213742"
  },
  {
    "caption": "(D). Association of RIF1 with Xist P2 in the Fa2L cells (black) and a wild type female mESC line (grey), also harbouring one castaneus and one 129 X chromosome. Allele-specific ChIP-qPCR primers were used, cast indicates association with the castaneus Xist P2 and 129 indicates association with the 129 Xist P2. Enrichments are presented relative to input DNA. Mean ±standard deviation from 3 independent experiments. p calculated by Student's two-tailed, paired t test comparing RIF1 association with the castaneus and with the 129 X chromosome Xist P2, ***p ≤ 0.001. Below, schematic of the Xist/Tsix alleles in the Fa2L undifferentiated cells. (E). Association of RIF1 with Xist P2 in the Fa2L cells (black) upon differentiation. The analysis was performed as in (D). Mean ±standard deviation from 3 independent experiments. p calculated by Student's two-tailed, paired t test comparing RIF1 association with the castaneus and with the 129 X chromosome Xist P2. *p ≤ 0.05. Below, schematic of the Xist/Tsix alleles in the Fa2L differentiated cells. (",
    "ncbi_link": "Xist: 
Tsix: 22097
Xist: 213742"
  },
  {
    "caption": "(A). Time course analysis of Xist expression by RT-qPCR during EB differentiation of female mESCs following knock down of Luciferase (Control, black) and Kap1 (Kap1 KD, grey), at the indicated timepoints. Data are presented as mean ±standard deviation from three independent experiments. Statistical significance was determined using 2-way ANOVA. Xist primers Xist ex3 F and Xist ex4 R were used. Normalisation was performed using a geometric mean consisting of the expression of Rplp0, Ubiquitin and Sdha. (*p ≤ 0.05). (B). RT-qPCR analysis of Xist expression levels during differentiation of the Fa2L cells, following expression of shRNA against Luciferase (Control, black) and Kap1 (Kap1 KD, grey), at the indicated timepoints. Mean ±standard deviation from a minimum of three independent experiments is presented. 2-way ANOVA was used to determine statistical significance. ns=not significant. (",
    "ncbi_link": "Luciferase: 
Kap1: 16483
Rplp0: 11837
Sdha: 66945
Xist: 213742"
  },
  {
    "caption": "(C). Tsix RNA levels in female mESCs infected with shRNA directed against Luciferase (Control, black) and KAP1 (Kap1 KD, grey), during differentiation. Mean ±standard deviation from four independent experiments are shown. Statistical significance was determined using 2-way ANOVA. (**p ≤ 0.01). Values have first been normalised to a geometric mean consisting of the expression of Rplp0, Ubiquitin and Sdha.",
    "ncbi_link": "Luciferase: 
KAP1: 16483
Kap1: 16483
Rplp0: 11837
Sdha: 66945
Tsix: 22097"
  },
  {
    "caption": "(D). RNA FISH analysis of Tsix expression during differentiation of female mESCs expressing an shRNA directed against Luciferase (control) or against Kap1 (Kap1 KD). Left: Cells with no (0, red), one (1, grey) and two or more (2, black) Tsix foci were counted in two independent experiments, shown averaged. Statistical significance was determined by χ2. A minimum of 110 cells were counted per each time point for each line (**p ≤ 0.01, ****p ≤ 0.0001). Right: examples of cells with one (top) or two (central and bottom) Tsix FISH signals. Scale bars: 5μm.",
    "ncbi_link": "Luciferase: 
Kap1: 16483
Tsix: 22097"
  },
  {
    "caption": "(A). ChIP-qPCR analysis of KAP1 association with the indicated sites in wild type female mESCs (Rif1+/+, same as used in Fig. 3B but without OHT) and during early differentiation. ZFP629 is a well-characterised KAP1 associated region (positive control). Xite A and C indicate two regions within the Tsix enhancer Xite, Tsix region 1 indicates Tsix major promoter, Tsix region 2 indicates the Dxpas34 region, Tsix region 3 indicates a region slightly downstream of the Dxpas34 region. P1 and P2 indicate the two Xist promoters, 5' indicates a region 2 kb upstream of Xist TSS. Inter1 is an intergenic region. See Appendix Fig. S2C for the positions of the primers within Xist and Tsix. The data are presented as mean ±standard deviation from three (2d EB and 1d EB) and two (ESCs) independent experiments. Statistical significance was calculated by Student's two-tailed unpaired t test comparing RIF1 association to Xist P2 and P1 in 2d EB versus 1d EB (*p ≤ 0.05 and ns=not significant). In the inset, Tsix RNA levels were quantified by RT-qPCR during the differentiation of wild type female ESCs shown in Fig. 4F. The average of two experiments is shown. Tsix values are normalised to a geometric mean consisting of the expression of Rplp0, Ubiquitin and Sdha. Error bars indicate standard deviations.",
    "ncbi_link": "Rif1: 51869
RIF1: 51869
Rplp0: 11837
Xite: 619209
Sdha: 66945
Tsix: 22097
Xist: 213742
ZFP629: 320683"
  },
  {
    "caption": "(C). KAP1 association with Xist promoter in two independent Rif1+/+ (Rif1+/+ +OHT, black) and two Rif1-/- (Rif1F/F +OHT, grey) female mESC cell lines. Ezr is an additional region known to be associated with KAP1 in mESCs. Enrichments are presented relative to input DNA. Mean ±standard deviation from a minimum of three independent experiments per cell line are displayed. Statistical significance was determined using Student's two-tailed, unpaired t test comparing the KAP1 association with Xist P2 and P1 in Rif1+/+ versus Rif1-/- cells (**p ≤ 0.01).",
    "ncbi_link": "Ezr: 22350
Rif1: 51869
Xist: 213742"
  },
  {
    "caption": "(C). HEXIM1 association with the Xist promoter (P1 and P2) in two independent Rif1+/+ and two Rif1-/- mESC lines, analysed by ChIP-qPCR. Tkbp1 and Myf5 are two control regions. As in the case of KAP1 association, deletion of Rif1 induces accumulation of HEXIM1 on Xist P1 and P2. Average ±standard deviation of two independent experiments. p values were calculated by two-tailed, unpaired, equal variance t-test. (**p ≤ 0.01, ***p ≤ 0.001).",
    "ncbi_link": "Tkbp1: 
KAP1: 16483
Myf5: 17877
Rif1: 51869
Xist: 213742"
  },
  {
    "caption": "(E). Upon infection of Fa2L cells with shRNA against Kap1 or control, against Luciferase, HEXIM1 association with P2 was analysed, on both alleles, by ChIP-qPCR. As in the case of KAP1, HEXIM1 shows preferential association with Xist P2 on the Cast allele (future Xa, Control). The association is lost upon knock down of Kap1 (Kap1 KD). Myf5 serves as a negative and Neat1 as a positive control regions.",
    "ncbi_link": "Luciferase: 
Kap1: 16483
KAP1: 16483
Myf5: 17877
Xist: 213742"
  },
  {
    "caption": "(A) Quantification of AURKB transcripts in non-IPF lung derived resident-fibroblasts treated with indicated mitogens for 16hrs. *P < 0.05, ***P < 0.0005, and ****P < 0.00005, 1-way ANOVA, (n=4).",
    "ncbi_link": "AURKB: 9212"
  },
  {
    "caption": "(B) Quantification of AURKB gene transcripts in isolated fibroblasts from non-IPF and IPF lung stromal cell cultures. **P < 0.005, unpaired t-test, (n=6).",
    "ncbi_link": "AURKB: 9212"
  },
  {
    "caption": "(D) Immunoblots of Aurkb and Aurka in total lung lysates of normal (CCSP/-) and fibrotic (CCSP/TGFα) mice fed with Dox for 6wks. Quantification was performed using phosphor imager software and normalization was done using loading control GAPDH. *P < 0.05, unpaired t-test, (n=4).",
    "ncbi_link": "CCSP: 22287
TGFα: 21802"
  },
  {
    "caption": "(E) Immunostaining was performed using AURKB antibody in lung sections of control (CCSP/-) and TGFα (CCSP/TGFα) mice on Dox for 6wks (n=6). Representative images were obtained at 20X (low; Scale bar: 100µm) and 63X (high; Scale bar: 30µm) magnification. Dashed box indicates area of the section showing in high magnification.",
    "ncbi_link": "CCSP: 22287
TGFα: 21802"
  },
  {
    "caption": "(A) Human IPF lung fibroblasts were transiently transfected with control or WT1 siRNA for 72hrs and AURKB transcripts were quantified. ****P < 0.00005, unpaired t-test, (n=4).",
    "ncbi_link": "AURKB: 9212
WT1: 7490"
  },
  {
    "caption": "(B) Lung-resident fibroblasts from TGFα mice on Dox for 4 wks were transiently transfected with control or WT1 siRNA for 72hrs and AURKB transcripts were quantified. ****P < 0.00005, unpaired t-test, (n=4).",
    "ncbi_link": "AURKB: 20877
TGFα: 21802
WT1: 22431"
  },
  {
    "caption": "(C) Immunoblot analysis of AURKB and WT1 in the lysates of non-IPF fibroblasts transduced with control or WT1-adenoviral particles for 72hrs. **P < 0.005, unpaired t-test, (n=3).",
    "ncbi_link": "WT1: 7490"
  },
  {
    "caption": "(D) Quantification of AURKB transcripts in primary fibroblasts from IPF lung treated with either control or WT1 siRNA and stimulated with media or TGFα (100ng/mL) for 16hrs. ****P < 0.00005, unpaired t-test, (n=4).",
    "ncbi_link": "AURKB: 9212
WT1: 7490"
  },
  {
    "caption": "(E) Primary lung-resident fibroblasts were isolated from stromal cultures of TGFα mice placed on Dox for 8 wks. Cell lysates were prepared, and the ChIP assay was performed with anti-WT1 antibody or normal rabbit IgG as a negative control using AURKB gene promoter-specific PCR primers. Non-immunoprecipitated DNA is represented as input DNA (product size, 104 bp). ***P < 0.0005, unpaired t-test, (n=2).",
    "ncbi_link": "AURKB: 20877
TGFα: 21802"
  },
  {
    "caption": "(F) AURKB-promoter luciferase activity was measured in HEK293 cells transfected with control or WT1 overexpressing (OE) vector. ****P < 0.00005, one-way-ANOVA, (n=6).",
    "ncbi_link": "AURKB: 9212
WT1: 7490"
  },
  {
    "caption": "(C) Lung sections from control and TGFα mice fed with Dox food for 4 wks were stained for AURKB (green) and Ki-67(red). Merged image shows cells that co-express AURKB and Ki-67 (yellow).",
    "ncbi_link": "TGFα: 21802"
  },
  {
    "caption": "(D) Quantification of Ki-67+ and AURKB+ double positive cells was performed using five confocal images per mice in control and TGFα mice. Images were obtained at 40X magnification. Scale bar: 50µm. ****P < 0.00005, unpaired t-test, (n=4).",
    "ncbi_link": "TGFα: 21802"
  },
  {
    "caption": "(E) Proliferation was measured in primary lung resident fibroblast isolated from either IPF lung or TGFα mice and treated with either control or AURKB siRNA. ****P < 0.00005, unpaired t-test, (n=9-11).",
    "ncbi_link": "AURKB: 9212
TGFα: 21802"
  },
  {
    "caption": "(F) Proliferation was measured in primary lung-resident fibroblasts isolated from stromal cultures of TGFα mice on Dox for 2 wks and transiently transfected with control or AURKB siRNA and stimulated with TGFα (20ng/mL) for 24hrs. ****P < 0.00005, 1-way ANOVA, (n=9-11).",
    "ncbi_link": "AURKB: 20877
TGFα: 21802"
  },
  {
    "caption": "(G) Quantification of CCNA2 and PLK1 transcripts in human IPF fibroblasts transiently transfected with control or AURKB siRNA for 72hrs. **P < 0.005, ***P < 0.0005, unpaired t-test, (n=3).",
    "ncbi_link": "AURKB: 9212
CCNA2: 890
PLK1: 5347"
  },
  {
    "caption": "(H) Lung sections from control and TGFα mice fed with Dox food for 6 wks were stained for AURKB (green) and αSMA (red). Images were obtained at 40X magnification. Scale bar: 50µm. (n=4).",
    "ncbi_link": "TGFα: 21802"
  },
  {
    "caption": "(I) Quantification of apoptotic cells using Incucyte ZOOM (Caspase-3/7- positive cells) in lung-resident fibroblasts isolated from IPF and TGFα mice on Dox for 6 wks and treated with control or AURKB siRNA for 72h. **P < 0.005, ****P < 0.00005, 2-way ANOVA, (n=4).",
    "ncbi_link": "AURKB: 9212
TGFα: 21802"
  },
  {
    "caption": "(J) Quantification of BAK, BAX and FAS gene transcripts in human IPF lung resident fibroblasts treated with either control or AURKB siRNA for 72hrs. **P < 0.005, ***P < 0.0005, unpaired t-test, (n=3).",
    "ncbi_link": "AURKB: 9212
BAK: 578
BAX: 581
FAS: 355"
  },
  {
    "caption": "(K) Quantification of Bak, Bax and Fas gene transcripts in lung resident fibroblasts isolated from TGFα mice and treated with either control or AURKB siRNA for 72hrs. *P < 0.005, **P < 0.005, unpaired t-test, (n=3).",
    "ncbi_link": "AURKB: 20877
Bak: 12018
Bax: 12028
Fas: 14102
TGFα: 21802"
  },
  {
    "caption": "(B) Proliferation was assessed using BrdU incorporation assay in fibroblasts isolated from TGFα mice lung and treated with indicated doses of barasertib for total of 48hrs. ***P < 0.0005, 1-way ANOVA, (n=9-11).",
    "ncbi_link": "TGFα: 21802"
  },
  {
    "caption": "(C) Primary lung resident fibroblasts isolated from TGFα mice on Dox for 4 wks were treated with vehicle or 5µM barasertib for 48hrs and immunostained using PCNA antibody. Images were obtained at 40X magnification. Scale bar: 50µm. The number of PCNA-positive cells and total DAPI-positive cells were quantified using MetaMorph image analysis software. Proliferation is indicated as the percentage of proliferating cells in total DAPI-positive cells. ****P < 0.00005, unpaired t-test, (n=3-4).",
    "ncbi_link": "TGFα: 21802"
  },
  {
    "caption": "(E) Quantification of Col1α, Col5α and Fn1 gene transcripts in total lung of mice treated with vehicle or barasertib.***P< 0.0005, ****P < 0.00005, 1-way ANOVA, (n=8 mice/group).",
    "ncbi_link": "Col1α: 12843///12842
Col5α: 53867///12832///12831
Fn1: 14268"
  },
  {
    "caption": "(C) Quantification of Aurkb, Plk1 and CcnA2 gene transcripts in total lungs of mice treated with vehicle or barasertib. **P< 0.005, ***P<0.0005, ****P < 0.00005, 1-way ANOVA, (n=8 mice/group).",
    "ncbi_link": "Aurkb: 20877
CcnA2: 12428
Plk1: 18817"
  },
  {
    "caption": "(D) Quantification of Col1α1, Col3α, Col5α, Col14, Col15, αSma, Ccna2, and Fas gene transcripts in total lungs of mice treated with vehicle or barasertib. *P< 0.05, **P<0.005 ***P<0.0005, ****P < 0.00005, 1-way ANOVA, (n=6 mice/group).",
    "ncbi_link": "αSma: 11475
Ccna2: 12428
Col14: 12818
Col15: 12819
Col1α1: 12842
Col3α: 12825
Col5α: 53867///12832///12831
Fas: 14102"
  },
  {
    "caption": "(C) PTCH1 inhibited the Endo H-resistant glycosylation of SMO. HEK293T cells were co-transfected with the SMO and PTCH1 expression plasmids. After 48 h, the cells were harvested, lysed, and treated with indicated glycosidases. Results shown are representative of three independent experiments.",
    "ncbi_link": "PTCH1: 19206
SMO: 6608"
  },
  {
    "caption": "(E) Shh increased the Endo H-resistant form of SMO. Cells were transfected as indicated for 24 h, and incubated with ShhN conditioned medium for an additional 24 h. Cells were harvested and analyzed as in (C). Results shown are representative of three independent experiments.",
    "ncbi_link": "Shh: 20423
ShhN: 20423"
  },
  {
    "caption": "(G) Shh increased the Endo H-resistant form of endogenous SMO in MEF cells. Results shown are representative of three independent experiments.",
    "ncbi_link": "Shh: 20423"
  },
  {
    "caption": "(A) Biotinylation of SMO by SAR1B-BirA* (asterisk denotes the R118G mutation in BirA) in a proximity-dependent biotinylation assay. The cells were transfected with plasmids encoding SMO and SAR1B-BirA*-FLAG. After 48 h, cells were treated with different doses of biotin for 4 h. Cells were harvested and lysates were dialyzed to remove free biotin. Biotinylated proteins were pulled down by streptavidin beads and subjected to immunoblotting analysis. (B) The cells were treated with different doses of biotin for 24 h. Cells were harvested, lysed, and subjected to procedure as shown in Fig. 2A.",
    "ncbi_link": "BirA: 948469
SAR1B: 51128
SMO: 6608"
  },
  {
    "caption": "(C) The GDP-locked SAR1B(G37A)-BirA* failed to label SMO, while the GTP-locked SAR1B(H79G)-BirA* could efficiently biotinylate SMO. The cells were transfected with plasmids expressing SMO and indicated SAR1B-BirA*. After 48 h, cells were treated with 15 μM biotin for 4 h. Then experiments were carried out as described in Fig. 2A.",
    "ncbi_link": "BirA: 948469
SAR1B: 51128
SMO: 6608"
  },
  {
    "caption": "(D) PTCH1 decreased SAR1B-BirA*-mediated biotinylation of SMO, but not LMAN1. The experiments were done similarly in Fig. 2A.",
    "ncbi_link": "BirA: 948469
PTCH1: 19206
SAR1B: 51128"
  },
  {
    "caption": "(C) The GDP-locked SAR1B(G37A)-BirA* failed to label SMO, while the GTP-locked SAR1B(H79G)-BirA* could efficiently biotinylate SMO. The cells were transfected with plasmids expressing SMO and indicated SAR1B-BirA*. After 48 h, cells were treated with 15 μM biotin for 4 h. Then experiments were carried out as described in Fig. 2A. (D) PTCH1 decreased SAR1B-BirA*-mediated biotinylation of SMO, but not LMAN1. The experiments were done similarly in Fig. 2A. (E) The Shh increased the binding of SAR1B to SMO. After transfection for 24 h, cells were incubated with the ShhN conditioned medium for an additional 24 h. Then 15 μM biotin was added into the culture medium for 4 h. The cells were harvested and analyzed as described in Fig. 2A.",
    "ncbi_link": "BirA: 948469
PTCH1: 19206
SAR1B: 51128
Shh: 20423
ShhN: 20423"
  },
  {
    "caption": "(C) SAR1B-BirA*-mediated biotinylation of the SMO variants. The experiments were done similarly in Fig. 2A.",
    "ncbi_link": "BirA: 948469
SAR1B: 51128
SMO: 6608"
  },
  {
    "caption": "(F) The ciliary localization of SMO variants. Smo-KO NIH3T3 cells were transfected with the EGFP fused SMO variants, incubated with serum starvation medium for 24 h to fully induce cilia formation, and treated with or without ShhN conditioned medium for 4 h. Cells were immunostained with the acetylated tubulin (red). Results shown are representative of three independent experiments. Scale bars: 5μm.",
    "ncbi_link": "EGFP: 
Smo: 319757
SMO: 319757"
  },
  {
    "caption": "(I) Gli-luciferase reporter assay in Smo-KO NIH3T3 cells. The cells were transfected with plasmids encoding SMO or SMO variants, GLI-promoted firefly luciferase and renilla luciferase. After 24 h, cells were incubated with a medium containing different amounts of ShhN for another 24 h.",
    "ncbi_link": "luciferase: 
Smo: 319757
SMO: 6608"
  },
  {
    "caption": "(A) Shh increased cholesterylation of SMO. HEK293T cells were transfected, harvested, and analyzed",
    "ncbi_link": "Shh: 20423"
  },
  {
    "caption": "(B) The SMO cholesterylation of Ptch1-KO NIH3T3 cells were increased comparing with WT cells.",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "(D) Cholesterylation of SMO(4A) was inhibited by PTCH1 and increased by ShhN.",
    "ncbi_link": "PTCH1: 19206
ShhN: 20423"
  },
  {
    "caption": "(F) The levels of CP-modified WT SMO and SMO(4A) were compared. 1.39% of SMO(WT) pellet samples and 11.1% of SMO(4A) pellet samples were loaded. Results shown are representative of three independent experiments.",
    "ncbi_link": "SMO: 6608"
  },
  {
    "caption": "(G) Quantification of CP-modified SMO shown in (F). Three independent experiments were quantified by Image J and expressed as a percentage of the total SMO.",
    "ncbi_link": "SMO: 6608"
  },
  {
    "caption": "(H, I) The stimulative /inhibitory effect of Shh/PTCH1 on SMO and SAR1B interaction was compromised by D95E mutation. The experiments were done the same as Fig. 2E.",
    "ncbi_link": "PTCH1: 19206
SAR1B: 51128
Shh: 20423
SMO: 6608"
  },
  {
    "caption": "(G) Effect of ALOD4 on the expression of Gli1 was measured by qRT-PCR. The cells were treated with ALOD4 for 1 h, and then incubated with ShhN conditioned medium for 5 h.",
    "ncbi_link": "Gli1: 14632"
  },
  {
    "caption": "(A, B) GRAMD1B increased cholesterylation of SMO. HEK293T cells were co-transfected with the SMO or SMO (4A) and GRAMD1B protein expression plasmids for 24 h, and then incubated with a cholesterol depletion medium (DMEM supplemented with 5% lipoprotein-deficient serum, 1 μM lovastatin and 10 μM mevalonate) for 12 h, followed by 2 μg/mL of CP treatment. The cells were harvested and analyzed as Results shown are representative of two independent experiments.",
    "ncbi_link": "GRAMD1B: 57476
SMO: 6608"
  },
  {
    "caption": "(C, D) GRAMD1B promoted SMO maturation. The expression plasmids of SMO or SMO(D95E) and GRAMD1B were transfected into SMO-KO HEK293T cells. After 12 h, cells were switched to a cholesterol depletion medium for 16 h and then added 50 μM MβCD-cholesterol for 8 h. Black bracket indicates mature glycosylated form.",
    "ncbi_link": "GRAMD1B: 57476
SMO: 6608"
  },
  {
    "caption": "(E) Expression of Gli1 mRNAs measured by qRT-PCR in NIH3T3 cells stably expressing GRAMD1B. After incubating in serum starvation medium for 16 h, cells were depleted of cholesterol by treatment with 1.5% HPCD for 0.5 h and then incubated in serum starvation medium containing 1 μM lovastatin, 10 μM mevalonate and 10 μM MβCD-cholesterol, ShhN as indicated for 24 h.",
    "ncbi_link": "Gli1: 14632
GRAMD1B: 57476"
  },
  {
    "caption": "(A) The cholesterol modification of endogenous SMO was decreased in NIH3T3 cells lacking Gramd1a, 1b, 1c, 2, and 3 (Gramd-5KO). The cells were incubated in a cholesterol depletion medium for 12 h, followed by 2 μg/mL of CP and ShhN for an additional 12h.",
    "ncbi_link": "Gramd1a: 52857"
  },
  {
    "caption": "(H) The Gli1 mRNA levels were measured in WT, Gramd-5KO, Gramd-5KO overexpression GRAMD1A, 1B, 1C NIH3T3 cells by qRT-PCR after treatment with or without ShhN conditioned medium for 8 h. Data are expressed as mean ± SEM from three technical replicates (****p < 0.0001, two-way ANOVA with Tukey's multiple comparisons test).",
    "ncbi_link": "Gli1: 14632
GRAMD1A: 57655"
  },
  {
    "caption": "(J) The GRAMD inhibitor AI3d decreased the mRNA levels of Gli1 in NIH3T3 cells. Cells were incubated in serum starvation medium for 16 h, depleted of cholesterol by 1.5% HPCD for 0.5 h, and then treated with serum starvation medium containing 1 μM lovastatin, 10 μM mevalonate and 1 μM AI3d for 6 h. Next, cells were incubated in the same medium containing ShhN and 10 μM MβCD-cholesterol for an additional 16",
    "ncbi_link": "Gli1: 14632"
  },
  {
    "caption": "(A) IFN‑α (left) and IFN‑β (right) production by WT and Irf3-/-Irf7-/- BMDCs plated at high density (2x105 cells/cm2) and stimulated with poly(I:C) (blue dots) or left unstimulated (grey dots). Dotted lines represent the ELISA threshold of detection. Data are representative of 2 independent experiments.",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "(B) CD86 and CD40 expression was quantified on WT (blue dots) and Irf3-/-Irf7-/- (orange dots) BMDCs plated at high density (2x105 cells/cm2) and stimulated with poly(I:C) or left unstimulated. Data are pooled from 2 independent experiments. (C) CD86 and CD40 expression on Irf3-/-Irf7-/- BMDCs plated at 2x105 cells/cm2 and stimulated with poly(I:C) (dark blue dots), IFN-α (light blue dots) or a combination of both (green dots). Data are representative of 2 independent experiments.",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "(A) CD86 and CD40 expression was quantified on WT (blue dots) and Irf3‑/‑Irf7‑/‑ (orange dots) DCs in non‑draining (ndLN) and draining (dLN) popliteal lymph nodes of WT and Irf3‑/‑Irf7‑/‑ mice injected with poly(I:C) or PBS. Data are pooled data from 2 independent experiments.",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "(D) Representative dot plots of CD86 and CD40 expression on WT (blue dots) and Irf3‑/‑Irf7‑/‑ (orange dots) DCs of chimeras injected with PBS or poly(I:C).",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "Monocyte recruitment in the draining lymph node requires collective DC activation (A) Representative dot plots showing the percentage of monocytes (CD11b+ Ly6Chigh cells, black box) present in popliteal dLN of WT:Irf3‑/‑Irf7‑/‑ chimeric mice injected with poly(I:C) (middle and right) or with PBS (left). CD11b+ Ly6Clow/int cells corresponded to neutrophils and were not included in the analysis.",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "Collective DC activation is essential for the generation of T cell responses. (H) Flow cytometric quantification of CD44high H‑2Kb‑OVA tetramer+ CD8+ T cells in the draining lymph node of 90:10 and 5:95 (WT:Irf3‑/‑Irf7‑/‑) chimeric mice injected with PBS or OVA+poly(I:C). Data are pooled from 2 independent experiments.",
    "ncbi_link": "Irf3: 54131
Irf7: 54123"
  },
  {
    "caption": "a) UVRAG is released from the ER membrane in cells overexpressing MTMR3. HeLa cells transfected with MTMR3-mStrawberry or the catalytically inactive mutant MTMR3C413S were stained with anti-UVRAG antibody and processed for confocal microscopy. Asterisks indicate MTMR3-transfected cells (left). The percentage of transfected cells with diffused staining of UVRAG was quantified (middle). Data are mean±s.d.; n = 240 cells collected from four independent experiments; **P0.01. Western blot analysis shows the levels of endogenous UVRAG in the presence or absence of MTMR3 (right).",
    "ncbi_link": "MTMR3: 8897"
  },
  {
    "caption": "(c) Mutation of the C2 domain leaves UVRAG unable to associate with the ER. HeLa cells expressing Flag-UVRAG (WT) or its K78A/R82A mutant were fixed and processed for confocal microscopy for co-localization with the ER marker PDI (top panel). Insets highlight the relative distribution of UVRAG at the ER. UVRAG and endogenous PDI expression were confirmed by immunoblotting (bottom panel). See Supplementary Fig. S9 for uncropped data. Scale bars, 10 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) The UVRAG C-terminal 270-442 region interacts with RINT-1. Cells (HEK293T) were co-transfected with HA-RINT-1, together with Flag-UVRAG or its mutant derivatives, and whole-cell lysates (WCLs) were immunoprecipitated (IP) with anti-Flag, followed by immunoblotting (IB) with an anti-HA antibody.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) UVRAG knockdown impairs the interaction of the RINT-1-ZW10 complex with COPI in an autophagy-independent manner. Cells (HEK293T) were transfected with control shRNA, UVRAG shRNA or Atg16L1 shRNA for 72 h. Whole-cell lysates (WCLs) were used for immunoprecipitation with anti-RINT-1 (first and third panels), anti-ZW10 (second panel), or anti-UVRAG (fourth panel), followed by immunoblotting with the indicated antibodies. Input represents 10% whole-cell lysates. Note that β′-COP interaction was suppressed by UVRAG knockdown but unaffected by Atg16L1knockdown. See Supplementary Fig. S9 for uncropped data. (",
    "ncbi_link": "Atg16L1: 55054
UVRAG: 7405"
  },
  {
    "caption": "(b) Retrograde transport of tsO45-VSVG-KDELR-YFP from the Golgi to the ER is inhibited by UVRAG knockdown. HeLa cells serially transfected with UVRAG shRNA or control shRNA, then with VSVG-KDELR-YFP expression vector, were incubated at 32°C (permissive condition) overnight. On shifting to 40°C (non-permissive condition), the ER-like distribution pattern of VSVG-KDELR-YFP was registered. Representative confocal images of the distribution pattern of VSVG-KDELR at 40°C and its co-localization with PDI are shown (upper panel). Data are mean±s.d., n = 100 cells obtained from three independent experiments; **P0.01 (bottom panel). Scale bars, 10 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) UVRAG interaction with bothPtdIns(3)P and RINT-1 is required for COPI-dependent retrograde transport, as shown by the redistribution of VSVG-KDELR from the Golgi to the ER. HeLa cells were transfected with control shRNA or UVRAG shRNA. The UVRAG-depleted cells were then complemented with empty vector, Flag-UVRAG, UVRAGΔ270−442, UVRAGK78A/R82A or UVRAGΔC2, along with the transfection of VSVG-KDELR-YFP. The ER pattern for the chimaeric KDELR was quantified (left panel). Data are the mean±s.d.; n = 200 cells obtained from three independent experiments; *P0.05; **P0.01. Endogenous and reconstituted UVRAG expression was confirmed by immunoblotting (right panel).",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(d) PtdIns(3)Pdepletion inhibits Golgi-to-ER retrograde transport of VSVG-KDELR. HeLa cells were transfected with empty vector, wild-type MTMR3, the C413S mutant of MTMR3, or treated with wortmannin or rapamycin, and then the ER pattern of VSVG-KDELR was quantified. UT, untreated. Data are the mean±s.d.; n = 100 cells for each group obtained from three independent experiments; **P0.01.",
    "ncbi_link": "MTMR3: 8897"
  },
  {
    "caption": "(a) Golgi morphology on UVRAG depletion. HeLa cells were transfected with control or UVRAG-specific shRNA for 72 h and subjected to electron microscopy analysis (left panel). When compared with control cells (left), the Golgi structure was swollen and fragmented in cells lacking UVRAG. The level of Golgi fragmentation was quantified (right panel). Data represent mean±s.d.; n = 50 cells obtained by gathering data from two independent experiments; *P0.05. Scale bars, 500 nm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) Depletion of UVRAG leads to cis-Golgi dispersion. HeLa cells were transfected with control shRNA or UVRAG-specific shRNA expressing GFP as an expression marker and then stained for GM130 (left panel; red; highlighted by arrows). Nuclei were stained with DAPI (blue). The dispersed distribution of GM130 in shRNA-transfected cells was quantified (middle panel). Data are the mean±s.d.; n = 500 cells obtained from five independent experiments. The expression of UVRAG and GM130 in treated cells is also shown (right panel). Scale bars, 10 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) The effect of UVRAG on membrane trafficking from the ER to the Golgi. HeLa cells serially transfected with UVRAG shRNA RINT-1 shRNA or control shRNA, then with VSVG-GFP expression vector, were incubated at 40°C (non-permissive condition) overnight. The cells were then shifted to 32°C (permissive condition) for 30 min to allow cargo transit from the ER to the Golgi. Before and after the temperature shift, the cells were fixed and labelled with anti-PDI and anti-GM130 antibodies to define the ER and Golgi region, respectively. Representative confocal microscopy images of the distribution pattern of the retrograde cargo at 40°C and 32°C are shown (left panel). The Golgi-like distribution pattern of VSVG-GFP was registered (right panel). Data are mean±s.d.; n = 100 cells from three independent experiments; **P0.01. Scale bars, 10 μm.",
    "ncbi_link": "RINT-1: 60561
UVRAG: 7405"
  },
  {
    "caption": "(d,e) UVRAG interaction with PtdIns(3)P and RINT-1 is required or Golgi integrity. (d) HeLa cells were transfected with control shRNA (first row) or UVRAG shRNA (second to sixth rows). The UVRAG-depleted cells, as indicated by Flag expression, were then transfected with empty vector (second row), UVRAGK78A/R82A-UVRAG (third row), UVRAGΔ270−442mutant (fourth row), UVRAGK78A/R82A mutant (fifth row), or UVRAGΔCCD mutant (sixth row), followed by confocal microscopy using anti-GM130 (red) for cis-Golgi staining, anti-Flag (purple) for the ectopically expressed UVRAG protein expression, and UVRAG for nuclei (blue). Asterisks indicate shRNA-transfected cells and arrows denote the cells reconstituted with GM130 (wild-type or mutant) expression. (e) The dispersed distribution of GM130 was quantified, and data represent the mean±s.d.; n = 200 cells from four independent experiments; *P0.05; **P0.01.",
    "ncbi_link": "UVRAG: Q9P2Y5///7405"
  },
  {
    "caption": "(c) Gel filtration analysis of UVRAG complex formation under normal conditions (untreated, UT) and after rapamycin-induced autophagy (50 nM). Affinity-purified UVRAG complexes from HCT116 cells stably expressing Flag-UVRAG were fractionated by Superose-6 gel filtration column and the eluates were analysed by western blotting for UVRAG, RINT-1, ZW10, beclin 1, PI(3)KC3 and Bif-1 proteins. Whole-cell lysates (2.5%) were used as the input (lane-1). The elution profile of each protein was quantified by densitometry analysis and normalized. Relative densitometry units were plotted against fraction number. Black arrows indicate the positions of the molecular weight size markers. Red arrows indicate the peak shift of the UVRAG eluates.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a-c) UVRAG interaction with beclin 1 and PtdIns(3)P, but not with RINT-1, is required for autophagy-induced Atg9 dispersal. (a) HeLa cells were stably transfected with control shRNA (first row) or UVRAG shRNA (second-sixth rows). The UVRAG-depleted cells were then transfected with empty vector (second row), Flag-UVRAG (third row), UVRAGΔ270−442 mutant (fourth row), UVRAGK78A/R82A mutant (fifth row) or UVRAGΔCCD mutant (sixth row), and incubated in complete medium (untreated, UT, first panel), starvation medium (HBSS 2 h, third panel), or treated with rapamycin (50 nM 2 h, second panel) or SMER28 (50 μM, 2 h, fourth panel). The distribution pattern of endogenous Atg9 (green) in the UVRAG (wild-type or mutant)-transduced cells (red) was analysed by confocal microscopy (a). Asterisks denote condensed (non-dispersed) Atg9 in UVRAG-depleted HeLa cells and arrows denote the cells complemented with wild-type or mutant UVRAG.",
    "ncbi_link": "UVRAG: Q9P2Y5///7405"
  },
  {
    "caption": "(b,c) The percentage of cells with Atg9 translocation was quantied (c) and the expression of UVRAG and actin was determined by immunoblotting (b). Data represent the means:d:; n D300 cells from three independent experiments; NS, not signicant; P <0:01; P <0:001. Scale bars, 10 m.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(d) Effect of knockdown of UVRAG, beclin 1 andRINT-1 on the translocation of Atg9 to the LC3-labelled autophagsomes during autophagy. Control-, UVRAG-, BECN1- or RINT-1-knockdown HeLa cells were incubated in complete medium (normal condition), starvation medium (HBSS, 2 h), or treated with rapamycin (100 nM, 2 h) or SMER28 (50 μM, 2 h). The cells were then stained for endogenous Atg9 (green) and LC3 (red) followed by confocal microscopy analysis (top and bottom left panels). The percentage of Atg9 vesicles co-localized with LC3+-autophagic puncta was quantified (bottom middle panel). Endogenous UVRAG, beclin 1 and RINT-1 protein expression are shown (bottom right). Data represent mean±s.d.; n = 200 cells obtained from three independent experiments. NS, not significant; *P0.05; **P0.01; ***P0.001. Scale bars, 10 μm.",
    "ncbi_link": "beclin 1: 8678
BECN1: 8678
RINT-1: 60561
UVRAG: 7405"
  },
  {
    "caption": "F. Representative pictures from tail wounds of 1-year-old Fbln7 WT and KO mice. G. Measurements of wound area over time in Fbln7 WT (N=5) and KO (N=7) mice.",
    "ncbi_link": "Fbln7: 70370"
  },
  {
    "caption": "H-J. Hematoxylin and eosin staining from tail sections of wounded Fbln7 WT vs. KO mice (H) and quantitation of the re-epithelialization length (I) and thickness at the healing front (J). Scale bar: 200 μm. N=3 WT and 5 KO mice.",
    "ncbi_link": "Fbln7: 70370"
  },
  {
    "caption": "H-J. K31 and K14 immunostaining in tail sections of 1-year-old Fbln7 WT vs. KO compared with 2-month-old Fbln7 KO mice (H) and the quantitation (I, J). Scale bar: 50 μm. N=5 for both WT and KO of 2-3-month-old mice (I). N=5 and N=7 for 1-year-old WT vs. KO, respectively (J). Data information (F-J)",
    "ncbi_link": "Fbln7: 70370"
  },
  {
    "caption": "A. Collagen IV immunostaining in tail sections of 1-year-old Fbln7 WT vs. KO. Dotted box regions are enlarged.",
    "ncbi_link": "Fbln7: 70370"
  },
  {
    "caption": "B. Quantification of Collagen IV basement membrane intensity per cell in Fbln7 KO mice normalized to WT mice. N=4 WT and N=6 KO mice. Graphs show mean ± S.D. Mann-Whitney test. **; P<0.01, ns; not significant.",
    "ncbi_link": "Fbln7: 70370"
  },
  {
    "caption": "(G) The morphology  (Left), migration  (Middle) and invasion  (Right) of metformin  adaptive Huh7  cells with (shTOM) or without (shNC) knockdown of TOMM34  are shown (5×104 cells for  Transwell assay). Scale bars, (Left) 25 μm, (Middle) and (Right) 100 μm. (n=3 biological replicates, Two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "The effects of TOMM34  on HCC lung metastasis   in the tail vein injection mouse  model (shTOM: shTOMM34, TOMM34  knockdown cells; Scale bars, (Left) 1000 μm, (Right) 25 μm. (n=5 mice  for each group, Student's t-test). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "The effects of TOMM34  on HCC lung metastasis   in the  tail vein injection mouse  model OE-TOM: OE-TOMM34, TOMM34  overexpressed cells). Scale bars, (Left) 1000 μm, (Right) 25 μm. (n=5 mice  for each group, Student's t-test). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 
TOMM34: 10953"
  },
  {
    "caption": "(L)  Western blot  analysis showing the effects of TOMM34  on the expression of EMT markers in HCC  cells (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells).",
    "ncbi_link": "TOM: 
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(C) Transmission electron microscopy (TEM) of Huh7  shNC and shTOM (shTOMM34) cells. Yellow arrowheads indicate mitochondria, bule arrowheads indicate nucleus, red arrowheads indicate endoplasmic reticulum. Scale bars, (Left) 20 μm, (Middle) 4 μm, (Right) 1 μm. (n=5 biological replicates, One-way ANOVA). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(G) Western blot  analysis showing the protein expression of the main mitochondrial respiratory chain complex subunit (shTOM: shTOMM34, TOMM34 knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells).",
    "ncbi_link": "TOM: 
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(E) The mRNA and protein expression  of ATP5B  in indicated cells were determined by qPCR  (n=3 technical replicates, Two-way ANOVA) or immunoblotting  (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34-overexpressed cells). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(F-G) Western blot  showing protein level of ATP5B  in Huh7  (F) or PLC/PRF/5 (G) cells treated with or without 10 mg/mL CHX  for 12 hours or 25 μM MG132  for 8 hours. Relative grey value of ATP5B  was calculated using Image J (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells; CHX, cyclohexane). (n=3 technical replicates, Student's t-test). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(B-C) Western blot showing the expression of indicated proteins in adaptive HCC  cells with or without ATP5B  silencing.",
    "ncbi_link": "ATP5B: 506"
  },
  {
    "caption": "(D-E) Transwell assays showing the migration  and invasion  of adaptive HCC  cells with or without the silence of ATP5B  (5×104 adaptive Huh7  cells, 1×105 adaptive PLC/PRF/5  cells), Scale bars, 100 μm. (n=3 biological replicates, Two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "ATP5B: 506"
  },
  {
    "caption": "(G) Western blot  showing the expression of EMT markers in cells with (shTOM) or without (shNC) knockdown of TOMM34 or overexpression of ATP5B.",
    "ncbi_link": "ATP5B: 506
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(H) Transwell assays showing the migration  and invasion  of indicated cells (5×104 cells; shTOM, shTOMM34, TOMM34  knockdown cells). Scale bars, 100 μm. (n=4 biological replicates, two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(C-D) Immunoblotting  of EMT markers of HCC  cells treated with or without 200 nM Gboxin  for 24 hours (shTOM: shTOMM34, TOMM34  knockdown cells; OE-TOM: OE-TOMM34, TOMM34  overexpressed cells).",
    "ncbi_link": "TOM: 
TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(E-F) Transwell assay  showing the migration  and invasion  of HCC  cells treated with or without 200 nM Gboxin  for 36 hours (5×104 cells; shTOM: shTOMM34, TOMM34  knockdown cells). Scale bars, 100 μm. (n=3 biological replicates, two-way ANOVA). Data information: Data are presented as means ± S.D.",
    "ncbi_link": "TOM: 10953
TOMM34: 10953"
  },
  {
    "caption": "(A) B cell development in Igh∆890/∆890 mice. The relative frequencies of the indicated cell types were determined by flow cytometric  analysis of  bone marrow  cells  from  Igh∆890/∆890 and Igh+/+ mice  at the age of 3-4 weeks, indicating a 1.3-fold increase of  pro-B cells and a moderate decrease at subsequent  B cell developmental stages in  Igh∆890/∆890 mice. Statistical data are shown as mean value with SEM. Data information: Statistical data were analyzed by multiple t-tests (unpaired and two-tailed with Holm-Sidak correction; A, ; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot (A, corresponds to one mouse.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(B) Two-color 3D  DNA-FISH  analysis of ex vivo sorted pro-B cells of the indicated genotypes with the RP23-340K14 (red) and RP24-275L15  (green) BAC probes (Fig 1A). Representative images are show above. Dot plots (below) show the distances measured between the two DNA  signals in individual Igh alleles (2,123 for Rag2-/-, 1,514 for Igh∆890/∆890 Rag2-/- and 502 for Vav-Cre Pax5fl/fl (Pax5∆/∆) Rag2-/-pro-B cells) together with the mean distance (red bar) and SEM determined for each genotype. In total, four independent DNA-FISH experiments were performed. Data information: Statistical data were analyzed by multiple t-tests (unpaired one-way ANOVA (Tukey post-hoc test; B); *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "Cre: 2777477
Igh: 111507
Pax5: 18507
Rag2: 19374
Vav: 7409"
  },
  {
    "caption": "(C, VH   gene  recombination analysis in ex vivo sorted  Igh∆890/∆890 and Igh+/+ pro-B cells, as determined by VDJ-seq experiments (C) The percentages of uniquely identified DJH and VDJH sequences are shown as mean percentage with SEM. Each dot corresponds to an independent VDJ-seq experiments performed with sorted pro-B cells from one mouse. Data information: Statistical data were analyzed by multiple t-tests (unpaired and two-tailed with Holm-Sidak correction; ; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot C, corresponds to one mouse.",
    "ncbi_link": "Igh: 111507
VH: 111507"
  },
  {
    "caption": "(B) Flow cytometric determination of the ratio of immature IgMb  (B6) to IgMa   (129) B cells in the bone marrow  of Igh∆890(B6)/+(129), IghP4V (B6)/+(129) and control Igh+(B6)/+(129) mice, which were generated by crossing Igh∆890/+, IghP4V/+ and Igh+/+ mice  on the C57BL/6 (B6) background with Igh+/+ mice  of the 129/Sv (129) strain. The rearranged Igh  alleles of the C57BL/6 and 129/Sv strains give rise to the expression  of IgMb  and IgMa, respectively. The IgMb  (B6) to IgMa  (129) ratio is shown as mean value with SEM (right). Data information: Statistical data were analyzed by multiple t-tests (unpaired and two-tailed with Holm-Sidak correction; B, ; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot (B, corresponds to one mouse.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(C) Summary of the ratios of immature IgMb  (B6) to IgMa  (129)  B cells, determined for the indicated six mouse  strains analyzed and shown as mean values with SEM. The ratio determined for control  Igh+(B6)/+(129) B cells was set to 1. Data information: Statistical data were analyzed by multiple t-tests (unpaired one-way ANOVA (Tukey post-hoc test; C, ; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot C, corresponds to one mouse.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(D) Comparison of the VDJ-seq  data obtained with  pro-B cells  of the Igh+/+ (black), Igh∆890/∆890 (white bars) and IghP4V/P4V (gray) genotypes. The different VH genes (horizontal axis) are aligned according to their position in the Igh  locus The usage of each VH gene (vertical axis) is shown as percentage of all VDJH and DJH recombination  events determined for each pro-B cell  type. The relative frequency of each VH gene is shown as mean value with SEM and is based on three independent VDJ-seq experiments for  pro-B cells of each genotype.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(A) Presence of open chromatin  and the active histone marks H3K27ac and H3K4me2 at the V8.8E enhancer in  pro-B cells. The location of the VH8-8  gene, V8.8E enhancer (dashed line) and PAIR5  element are shown together with the mm9  genomic coordinates of mouse chromosome 12. The VH8-8 gene with 500 bp of its upstream and downstream sequences (indicated by violet overlay) was inserted with the Floxin method at the deletion point of the Igh∆890 allele to generate the IghV8-8  allele",
    "ncbi_link": "Igh: 111507
VH8-8: 780938
V8-8: 780938
mm9: 109279847"
  },
  {
    "caption": "(B, Flow-cytometric analysis (B) of GFP expression  are shown for  pro-B, pre-B,  immature B  and recirculating B cells from the bone marrow of IghP4GV/P4GV (dark green, n=16), IghP4GV/+ (light green, n=12) and control Igh+/+ (black, n=13) mice.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "C) geometric mean fluorescence intensity measurements (MFI, C) of GFP expression  are shown for pro-B,  pre-B, immature B and  recirculating B cells  from the bone marrow of  IghP4GV/P4GV (dark green, n=16),  IghP4GV/+ (light green, n=12) and control  Igh+/+ (black, n=13) mice. Geometric mean fluorescence intensity measurements (C) are shown as mean values with SEM.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "G) Absence of GFP expression  in DN (CD4-CD8-) and  DP (CD4+CD8+)  T cells, geometric mean fluorescence intensity measurements (G) of GFP expression  in thymocytes  from the indicated mice. Geometric mean fluorescence intensity measurements (G) are shown as mean value with SEM based on 12 (Igh+/+), 11 (IghP4GV/+) or 12 (IghP4GV/P4GV) independent replicates.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(A, B) Flow-cytometric analysis (A) and geometric mean fluorescence intensity measurements (MFI, B) of GFP expression  are shown for pro-B, pre-B, immature B and  recirculating B cells from the bone marrow  of IghP4GV/+ (green, n=6), IghP4∆Pax5GV/+ (yellow, n=5), IghP4∆CtcfGV/+ (brown, n=4) and control Igh+/+ (black, n=4) mice. Geometric mean fluorescence intensity measurements (B) are shown as mean value with SEM. Data information: Each dot corresponds to one mouse.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(C, D) Activation of the PAIR4-V8.7E  module in thymocytes  upon loss of CTCF   binding at PAIR4, as shown by flow-cytometric  analysis (C) and geometric mean fluorescence intensity measurements (MFI, D) of GFP expression  in DN, DP, CD4+  and CD8+ thymocytes of IghP4∆CtcfGV/+ (light brown, n=5) and  IghP4∆CtcfGV/P4∆CtcfGV (dark brown, n=6) mice  compared with control Igh+/+ (black, n=7) mice. Geometric mean fluorescence intensity measurements (D) are shown as mean value with SEM. Data information: Each dot corresponds to one mouse.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(B, C) Flow-cytometric  analysis (B) and geometric mean fluorescence intensity measurements (MFI, C) of YFP expression  are shown for MPPs  (LSK), LMPPs, ALPs  and BLPs  from the bone marrow  of Rosa26LSL-YPF/+ IghCμCre/+ (violet) and control  Rosa26LSL-YPF/+ Igh+/+ (black) mice. Geometric mean fluorescence intensity measurements (B) are shown as mean value with SEM and have been normalized by setting the mean value obtained with Igh+/+ cells to 1. Data information: Each dot corresponds to one mouse.",
    "ncbi_link": "Cre: 2777477
Rosa26: 14910
Igh: 111507"
  },
  {
    "caption": "Flow-cytometric  analysis (E) of GFP expression  are shown for MPPs  (LSK), LMPPs, ALPs, BLPs,  pro-B, pre-B, immature B and recirculating B cells from the bone marrow  of IghEμG/+ (light blue), IghEμG/EμG (dark blue) and control Igh+/+ (black) mice.",
    "ncbi_link": "Igh: 111507"
  },
  {
    "caption": "(F) Representative fluorescence micrographs of A549 cells of the indicated genotypes. Cells were either left untransduced (mock) or transduced with PIDD1-V5 lentiviral vectors expressing the PIDD1 non-cleavable derivative (PIDD1S446A-S588A) or truncations thereof. Blow-ups without Hoechst 33342 are magnified 2.5X. Scale bar: 5 μm.",
    "ncbi_link": "PIDD1: 55367"
  },
  {
    "caption": "(E) Movie stills of a representative RPE1 cell stably expressing CETN1-GFP treated with DHCB and subjected to time-lapse video microscopy in the presence of SiR-DNA. Time is expressed in minutes, relative to anaphase onset. The dashed line indicates the plasma membrane of the cell of interest, arrowheads indicate the centrosomes' position.",
    "ncbi_link": "GFP: 
CETN1: 1068"
  },
  {
    "caption": "(F) Centrosomal distance over time in RPE1 cells stably expressing CETN1-GFP and treated with DHCB. Time zero corresponds to the frame preceding anaphase onset. Coloured dots (lower panel) summarize the clustering time for each cell, mean ± standard deviation in black. Data calculated from four-dimensional imaging as in (E). N = 10 cells.",
    "ncbi_link": "GFP: 
CETN1: 1068"
  },
  {
    "caption": "(C) RT-qPCR analysis of PIDD1 mRNA expression in A549 cells upon treatment with increasing doses of Nutlin 3a (i.e. 3.3 μM or 10 μM) using two independent probes. The average fold of induction ± standard deviation is shown. N = 3 biological replicates with two technical replicates each. Comparisons were performed between treatments of every genotype and the corresponding treatment of wild type (WT) cells",
    "ncbi_link": "PIDD1: 55367"
  },
  {
    "caption": "E) Representative western blot of the solubility analysis of GK variants upon overexpression in E. coli K12. Bands show Soluble (Sol) and Pellet fractions after centrifugation at 17,100 g for 15 mins. \"-DnaK\" indicates expression in E. coli K12 DnaK knockout line, \"+ Dnak\" indicates co-expression of pKJE7, encoding DnaK, DnaJ and GrpE.",
    "ncbi_link": "DnaK: "
  },
  {
    "caption": "G) Structured Illumination Microsopy (SIM) images of E. coli after three hours of expression of one of the GK variants. GFP fluorescence is shown in green. \"ΔDnaK\" indicates expression in E. coli K12 DnaK knockout line, \"+ Dnak\" indicates co-expression of pKJE7, encoding DnaK, DnaJ and GrpE.",
    "ncbi_link": "DnaK: "
  },
  {
    "caption": "Microautophagic degradation of peroxisomes is not observed in a vacuolar protease-negative strain (STK7) of P. pastoris. Kinetics of morphological changes in vacuoles and peroxisomal GFP-SKL during (a) glucose adaptation and (b) ethanol adaptation. (c) Fluorescence images taken after 2 h of glucose adaptation. Arrows show GFP-SKL in vacuolar matrix. Some cells showed diffusion of GFP-SKL into the vacuolar matrix.",
    "ncbi_link": "vacuolar protease: 855949"
  },
  {
    "caption": "(a) Visualization of alcohol oxidase activity in colonies after (a) glucose adaptation for 8 h and ethanol adaptation for 24 h in wild-type (strain PPY12) and pag mutant cells (strains STK1-STK6, Materials and Methods) of P. pastoris. (b) Western-blot analysis of samples taken from cultures shifted from methanol to glucose for the indicated time. Antibodies used were AOX, alcohol oxidase; F1, mitochondrial F1β subunit; G6PDH, glucose-6-phosphate dehydrogenase. Growth curve of the wild-type strain PPY12 and the pag4 mutant (strain STK4) after shift from methanol to glucose.",
    "ncbi_link": "pag4: 853034"
  },
  {
    "caption": "Fluorescence images of (a) pag2 (strain STK2) and (b) pag3 (strain STK3) mutants of P. pastoris after a 3 h shift to glucose. (b) Arrows show deeply invaginated structures of vacuolar membranes surrounding peroxisomes in the pag3 mutant.",
    "ncbi_link": "pag2: 853219
pag3: 851929"
  },
  {
    "caption": "Fluorescence images of the pag4 (strain STK4) mutant of P. pastoris after (a) 0, (b) 3, or (c) 6 h of glucose adaptation. The vacuolar membrane proliferated extensively and surrounded peroxisomes during glucose adaptation.",
    "ncbi_link": "pag4: 853034"
  },
  {
    "caption": "Microautophagy of peroxisomes in a pex1-ts mutant (strain SJH242) of P. pastoris expressing GFP-SKL from the constitutive glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter at the restrictive temperature for peroxisome assembly (34°C). (a) Kinetics of peroxisome degradation at 34°C. Strain SJH242 was induced on methanol at 23°C, and glucose adaptation was performed at 34°C. (b) Changes in vacuole morphology were seen even in the absence of normal peroxisomes. At 0 h, SJH242 cells were grown at 34°C when GFP-SKL was diffuse in the cytosol and many vacuoles showed spherical morphologies. After 2 h, ∼20-30% vacuoles showed complicated membrane structures representative of stage 2 cells.",
    "ncbi_link": "GAPDH: 
pex1: 853636"
  },
  {
    "caption": "(A) In vivo fundusimage of an AAV-injected rd1mouse expressing ReaChR-mCitrine driven by the hSyn promoter (AAV2-hSyn:ReaChR-mCitrine); transduced RGCs are visible as green puncta.",
    "ncbi_link": "rd1: 18587
hSyn: 8224///6854///6853"
  },
  {
    "caption": "(A) Examples of local field potential (LFP) traces in response to light flashes at 595 nm (light stimulus is shown as orange bar; 1.25 × 1017 photons cm-2 s-1). (B) Spike raster plots in response to 200 repetitions of the same light stimulus. (C) Averaged spike responses shown as peristimulus time histograms (PSTH, bin size: 5 ms) based on the spike raster plots. Top-row: WT-mice, middle row: rd1 control mice, bottom-row: ReaChR-treated rd1 mice. (D) ReaChR-induced cortical responses (spikes and LFP) as a function of light intensity at (595 nm) demonstrating that ReaChR-treated rd1 mice (n = 4) can detect light in the visual cortex at intensities well below the safety threshold allowed for the humanretina. Data presented as mean ± SEM.",
    "ncbi_link": "ReaChR: 
rd1: 18587"
  },
  {
    "caption": "(A) Locomotory behavior of a representative rd1 and ReaChR-treated mouse during illumination with light at 590 nm in an open field arena (irradiance measured at the level of the mice's eyes was ~1015 photons cm-2 s-1, cumulative activity trajectories are shown as red traces after 2 min of illumination), see also EV Movie 1 and EV Movie 2. (B) Mean velocities of the ReaChR-treated and rd1mice analyzed over a duration of 2 min at light onset. The mean velocity of ReaChR-treated mice were significantly reduced than rd1mice (P = 0.006, one-tailed t-test) upon illumination. Mean ± SEM are shown for each group. ReaChR-treated rd1 (n = 11), rd1 (n = 12).",
    "ncbi_link": "ReaChR: 
rd1: 18587"
  },
  {
    "caption": "(C) Light/dark box test. Percentage of time mice spent in the light compartment as a function of light intensity (WT, n = 9; rd1, n = 9; ReaChR-treated n = 7). Mean ± SEM are shown for each group. (D) Percentage of time rd1 (n = 9), WT (n = 9) and ReaChR-treated (n = 7) mice spent in the light compartment for an illumination intensity of 2.11 × 1015 photons cm-2 s-1. Both WT as well as ReaChR-treated mice spent significantly less time in the light compartment than the rd1mice (P < 0.0001, ordinary one-way ANOVA). *** and **** indicates significance levels determined by Tukey's multiple comparisons test for rd1 vs. WT and rd1 vs. ReaChR-treated. See also EV Movie 3 for the response of a representative ReaChR-treated rd1 mouse plotted in (D).",
    "ncbi_link": "ReaChR: 
rd1: 18587"
  },
  {
    "caption": "(A) Vertical section of macaqueretinal explant transfected with AAV2 hSyn:ReaChR-mCit after 10 days of incubation exhibiting mCitrine expresssion densely in neuronal processes in the GCL. (B) Vertical section of macaqueretinal explant transfected with AAV8 Y447 733F-CAG:ReaChR-GFP after 3 days of incubation. GFP expression was primarily observed in the cell bodies but also in processes of RGCs; green: endogenous GFP fluorescence; blue: DAPI; outer nuclear layer (ONL). scale bars = 10 µm.",
    "ncbi_link": "CAG: 
hSyn: 6853///8224///6854"
  },
  {
    "caption": "(A) Humanretinal explant, prepared from the far periphery, infected with an AAV8 Y447 733F-CAG :ReaChR-GFP, placed on a multi-electrode array chip (left); GFP epifluorescence of the same explant following 12 days of incubation is shown on the right. Scale bars: 100 µm. The location of two cells that responded to repeated 2 s full field stimulations of orange light (600 nm) are highlighted.",
    "ncbi_link": "CAG: "
  },
  {
    "caption": "(B) Sashimi plots comparing muscle RNA sequencing reads in P1 (red) and two control muscle samples (blue and green) at the exons 3-5 of BET1.",
    "ncbi_link": "BET1: 10282"
  },
  {
    "caption": "(D) HeLa-cells stably expressing the pC4-reporter were transfected with control siRNA (ctrl) or two independent siRNAs (#1 and #2) directed against BET1 (siRNA #1 is shown in figure EV 2B). 2d post-transfection the pC4-secretion assay was performed for 0 and 10 min post induction of secretion. Representative images are shown (upper panel ctrl and lower panel #2 siRNA, respectively. Scale bar: 20 µm. Right panels represent magnifications of dashed areas.",
    "ncbi_link": "BET1: 10282"
  },
  {
    "caption": "(A) Volcano plot of AP-MS data using HA-BET1 or Ile51Ser.",
    "ncbi_link": "HA: 
BET1: 10282"
  },
  {
    "caption": "(B) Co-IPs using HA-tagged constructs expressed in HEK293 cells. As baits HA-tagged proteins were immunoprecipitated with anti-HA beads. IP samples and cell lysates were subjected to immunoblotting with α-HA, α-ERGIC-53, α-BET1, α-SEC22b, α-GOSR2 and α-GAPDH antibodies, respectively.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "Ribosome occupancy map at the LINC00665 locus. MCF10A were either mock-treated or treated with TGF-β and Ribosome profiling on three biological replicates were shown.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Relative levels of CIP2A-BP were determined by polysome profiling and qRT-PCR in MCF-10A and TNBC cells either mock treated or treated with TGF-β. Relative levels of LINC00665 were determined by qRT-PCR in MCF-10A and TNBC cells either mock treated or treated with TGF-β.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Upper: putative ORFs in LINC00665. Lower: The ORFs were constructed into pcDNA3.1 vector and transfected to MCF-10A cells for 24h. The ORFs-His fusion proteins were determined by western blot with anti-His antibody.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Diagram of the His fusion constructs. The start codon ATG of the LINC00665 ORF is mutated to ATT. The indicated constructs were stably expressed in MDA-MB-231 cells, micropeptide CIP2A-BP was immuno-stained using anti-His (I) and anti-CIP2A-BP antibodies (K) respectively; CIP2A-BP-His fusion protein levels were determined by western blotting with anti-His and CIP2A-BP antibodies",
    "ncbi_link": "His: 
LINC00665: 100506930"
  },
  {
    "caption": "MCF-10A cells were first transfected with anti-LINC00665 translation-blocking antisense oligo, then micropeptide CIP2A-BP was detected.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Migration and invasion of TNBC cells transfected with LINC00665 ORF and control lentiviruses for 48h. Right panel is the quantification of TNBC cells that migrated through the membrane without the Matrigel (upper) and invaded through Matrigel-coated membrane (lower).",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Wound-healing assay on Hs578T and MDA-MB-231 cells transfected with LINC00665 ORF expressing and control lentiviruses. The wound edges were photographed at the indicated time points after wounding. Right panel is the quantification of the relative wound healing area.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "Chromatin immunoprecipitation showing Smad4 occupancy at the 4E-BP1 locus in TNBC cells. Co-precipitated DNA was analyzed for amplicons A-E by qPCR. Values represent the enrichment of bound protein fractions relative to input.",
    "ncbi_link": "4E-BP1: 1978"
  },
  {
    "caption": "Luciferase reporter assay was performed in Hs578T (F) and MDA-MB-231 (G) cells following co-transfection with wildtype or mutant 4E-BP1 promoter fragment and Smad4 over-expressed, or knocked down and respective controls for 36h and treatment with TGF-β for 24h. The reporter constructs were expressing the luciferase gene under 4E-BP1 promoter segment or 4E-BP1 promoter deleted 0 to +200 region.",
    "ncbi_link": "luciferase: 
4E-BP1: 1978
Smad4: 4089"
  },
  {
    "caption": "Smad4 siRNA and corresponding control transfected TNBC cells were cultured with or without TGF-β. The indicated proteins were determined by Immunoblotting analysis.",
    "ncbi_link": "Smad4: 4089"
  },
  {
    "caption": "4E-BP1 siRNA and corresponding control transfected TNBC cells were cultured with or without TGF-β. The indicated proteins were determined by immunoblotting analysis.",
    "ncbi_link": "4E-BP1: 1978"
  },
  {
    "caption": "LINC00665 ORF-His plasmid was transfected into MDA-MB-231 cells. Whole-cell lysates were subjected to co-immunoprecipitation using anti-His antibody and immunoblot analysis with CIP2A antibody to verify that CIP2A bound to CIP2A-BP.",
    "ncbi_link": "His: 
LINC00665: 100506930"
  },
  {
    "caption": "LINC00665 ORF-His plasmid was transfected into MDA-MB-231 cells. Whole-cell lysates were subjected to co-immunoprecipitation by CIP2A antibody and immunoblot analysis with CIP2A-BP antibodies to verify that CIP2A-BP bound to CIP2A.",
    "ncbi_link": "His: 
LINC00665: 100506930"
  },
  {
    "caption": "LINC00665 ORF-His plasmid was transfected into MDA-MB-231 cells. Whole-cell lysates were treated with 30 mg/mL RNase A for 30 min, the indicated complexes were co-immunoprecipitated by anti-His or anti-CIP2A antibody, and CIP2A or micropeptide CIP2A-BP were detected.",
    "ncbi_link": "His: 
LINC00665: 100506930"
  },
  {
    "caption": "The expression levels of the indicated proteins were detected by immunoblotting analysis in CIP2A-BP KO, LINC00665 ORF overexpressed (OE) and respective controls of TNBC cells.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "PP2A activity was measured using a protein phosphatase assay kit. PP2A activity assay was performed to evaluate PP2A activity in CIP2A-BP KO, LINC00665 ORF overexpressed (OE) and respective control TNBC cells.",
    "ncbi_link": "LINC00665: 100506930"
  },
  {
    "caption": "MDA-MB-231 cells were transfected with anti-CIP2A siRNAs. Whole-cell lysates of these cells were subjected to immunoblot analysis with CIP2A, CIP2A-BP, PP2Ac, p-AKT, AKT and β-actin antibodies.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "CIP2A-BP KO, LINC00665 ORF overexpressed (OE) and respective control MDA-MB-231 cells were transfected with anti-CIP2A siRNAs. PP2A activity assay was performed to evaluate PP2A activity in the indicated cells.",
    "ncbi_link": "CIP2A: 57650
LINC00665: 100506930"
  },
  {
    "caption": "Macroscopic and histological analysis of the lungs of 140 days old MMTV-PyMT mice; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "Immunohistochemistry (IHC) staining of p-AKT of mammary tumors from MMTV-PyMT;CIP2A-BP+/+ or MMTV-PyMT;CIP2A-BP-/- mice. Lower panels show higher-magnification images of insets in upper panels. Right panel is the quantification of IHC staining p-AKT .",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "MMTV-PyMT mice were injected with CIP2A-BP or svCIP2A-BP via mammary fat pad. Macroscopic and histological analysis of the lungs of 140 days old MMTV-PyMT mice; lung metastatic nodules were visualized 8 weeks post-transplantation (5 mice per group). Right panel is the quantification of pulmonary metastases.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "Representative IHC images of p-AKT of mammary tumors from MMTV-PyMT mice that were injected with CIP2A-BP or svCIP2A-BP via mammary fat pad; Lower panels show higher-magnification images of insets in upper panels. Right panel is the quantification of IHC staining p-AKT.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "(e) Colocalization of UVRAG-C-Vps in early endosomes. HeLa cells were co-transfected with EGFP-Vps16 and Flag-UVRAG, stained with antibodies to LAMP1, LAMP2, EEA1 and Rab5, followed by confocal microscopy. All images are representative of at least three independent experiments. Scale bars, 5 μm. The raw data for a and b are shown in Supplementary Information, Fig. S6",
    "ncbi_link": "UVRAG: 7405
Vps16: 64601"
  },
  {
    "caption": "(a) The N-terminal C2 domain or the C-terminal region of UVRAG interacts individually with Vps16. 293T cells were co-transfected with HA-Vps16, together with vector, Flag-UVRAG or Flag-UVRAG mutants. WCLs were immunoprecipitated with anti-Flag followed by immunoblotting with an anti-HA antibody.",
    "ncbi_link": "Vps16: 64601"
  },
  {
    "caption": "(b) HeLa cells were transfected with EGFP-Vps16 together with Flag-UVRAG mutants as indicated and stained with anti-Flag (red), followed by confocal microscopy. Scale bars, 5 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) Interactions of the UVRAG C-terminal truncated mutants with Vps16. At 48 h post-transfection with HA-Vps16 and Flag-UVRAG C-terminal mutants, 293T WCLs were immunoprecipitated with anti-Flag, followed by immunoblotting with anti-HA.",
    "ncbi_link": "UVRAG: 7405
Vps16: 64601"
  },
  {
    "caption": "(d) UVRAG C2 domain or C-terminal region deletion abolishes Vps16 binding. At 48 h post-transfection with HA-Vps16 together with Flag-UVRAG or its mutants, 293T WCLs were immunoprecipitated with anti-Flag followed by immunoblotting with an anti-HA antibody.",
    "ncbi_link": "UVRAG: 7405
Vps16: 64601"
  },
  {
    "caption": "(a) HeLa.Vec and HeLa.UVRAG cells transfected with HA-Vps16 and GFP-LC3 were treated with 2 μM rapamycin for 2 h, and processed for confocal microscopy (left panel; scale bars, 5 μm). The percentage of GFP-LC3 punctae positive for HA-Vps16 staining was quantified (right panel; data are mean ± s.e.m., n = 60, *P 0.01).",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405
Vps16: 64601"
  },
  {
    "caption": "(b) Effects of Vps16 on UVRAG-mediated autophagosome formation. Light microscopic quantification of autophagosomes in HeLa.Vec and HeLa.UVRAG cells (upper left panel) or in HCT116.Vec and HCT116.UVRAG cells (bottom left panel) when transfected with GFP-LC3 together with control siRNA or Vps16 siRNA (data are mean ± s.e.m., n = 60 for HeLa cells; n = 450 for HCT116 cells, *P 0.01; **P 0.001). Immunoblotting of Vps16 and tubulin are shown in the right panel.",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405
Vps16: 64601"
  },
  {
    "caption": "(a) UVRAG enhances the colocalization efficiency of GFP-LC3 with LAMP1. HeLa.Vec and HeLa.UVRAG cells transfected with GFP-LC3 were either untreated or treated with rapamycin (2 μM) in the absence or presence of bafilomycin A1 (0.1 μM) and stained for LAMP1. Insets highlight the colocalization. The percentage of LAMP1-positive autophagosomes was calculated in each setting (data are mean ± s.e.m., n = 200; 5 independent experiments, **P 0.01; *P 0.05).",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405"
  },
  {
    "caption": "(b) UVRAG enhances the acquisition of CD63 by autophagosomes. The GFP-LC3-transfected HeLa.Vec and HeLa.UVRAG cells were treated as described in a and stained for CD63 and the percentage of CD63-positive autophagosomes was calculated (data are mean ± s.e.m., n = 200, **P 0.01; *P 0.05).",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405"
  },
  {
    "caption": "(c) UVRAG promotes autophagic degradation of long-lived proteins. HeLa.Vec and HeLa.UVRAG cells were incubated for 16 h with L-3H-Leu (1 μCi ml-1). The degradation of long-lived proteins was measured at the indicated time points in complete medium (NC), EBSS alone (Starv.), or EBSS + 0.1 μM bafilomycin A1 (Starv.+BalfA1). Results (data are mean ± s.e.m. of triplicates) are representative of 2 independent experiments. Scale bars, 5 μm.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(a) Colocalization of GFP-LC3 and LAMP1. HeLa cells expressing wild-type or mutant UVRAG were transfected with GFP-LC3 and incubated under normal conditions or treated with rapamycin (2 μM). Autophagosome fusion with LAMP+ structures was analysed by confocal microscopy (left panel; rapamycin-treated) and quantified (right upper panel; data are mean ± s.e.m., n = 100). Arrows and insets show the LAMP1+ autophagosomes. The number of GFP-LC3-positive dots per cell was counted using a fluorescence microscope (right bottom panel; data are mean ± s.e.m., n = 60, *P 0.05; **P 0.0001).",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405"
  },
  {
    "caption": "(b) Vps16 or Vps18 knockdown inhibits UVRAG-mediated autophagosome maturation. HeLa.Vec (left) and HeLa.UVRAG (right) cells were transfected with GFP-LC3 together with control siRNA, Vps16 siRNA, or Vps18 siRNA, followed by confocal microscopy. Arrows in the top panel denote the autophagosomes with LAMP1 staining. Immunoblotting of Vps16, or Vps18 and tubulin are shown in the middle panel. The percentage of LAMP1+ autophagosomes was calculated (data are mean ± s.e.m., n = 50, *P 0.05). Scale bars, 5 μm. The raw data of the immunoblots are shown in Supplementary Information, Fig. S6.",
    "ncbi_link": "LC3: 440738///81631///84557
UVRAG: 7405
Vps16: 64601
Vps18: 57617"
  },
  {
    "caption": "(a) UVRAG expression promotes the recruitment of Rab7 GTPase to autophagosomes. HeLa.Vec and HeLa.UVRAG cells transfected with GFP-Rab7 and RFP-LC3 were maintained either under normal conditions (NC) or treated with rapamycin, followed by confocal microscopy. Insets highlight the Rab7 acquisition of autophagosomes. The percentage of Rab7+-autophagosomes was quantified (right panel; data are mean ± s.e.m., n = 60, ***P 0.001; **P 0.01). Scale bars, 5 μm.",
    "ncbi_link": "LC3: 440738///81631///84557
Rab7: 7879///338382
UVRAG: 7405"
  },
  {
    "caption": "(b) Rab7 GTPase activity is increased with UVRAG expression. At 48 h post-transfection with GFP-Rab7 together with vector, UVRAG or UVRAGΔN(1-147) vector, 293T WCLs were used for immunoprecipitation with anti-GFP, followed by the Rab7 GTPase activity assay. Left panel: Autoradiographs of the GTP hydrolysis products analysed by TLC. Right panel: Quantification of the percentage of GTP hydrolyzed by Rab7 (data are mean n = 2 independent experiments).",
    "ncbi_link": "Rab7: 7879///338382
UVRAG: 7405"
  },
  {
    "caption": "(c) Increased Rab7-RILP interaction UVRAG is expressed. HCT116.vector, HCT116.UVRAG and HCT116.UVRAGΔN(1-147) cells were transfected with GFP-Rab7 together with the GST-tagged Rab7 binding domain of RILP (GST-RILPRBD, residues 243-318). WCLs were used for GST pulldown, followed by immunoblotting with an anti-GFP antibody. The raw data of the immunoblots are shown in Supplementary Information, Fig. S6.",
    "ncbi_link": "Rab7: 7879///338382
RILP: 83547
UVRAG: 7405"
  },
  {
    "caption": "(a) EGF-stimulated endocytosis and post-endocytic trafficking. Uptake of Alexa Fluor 488-EGF (green) by HCT116.Vec (left panel) and HCT116.UVRAG (right panel) cells was followed by confocal microscopy. At the indicated times, cells were fixed and stained with antibodies to LAMP1 (red), and Topro-3 (blue, to stain the nucleus). Magnified images of the insets (fourth row) highlight trafficking of EGF towards LAMP1-positive structures.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(b) EGFR degradation. HCT116.Vec, HCT116.UVRAG and HCT116.UVRAGΔN(1-147) cells were treated with EGF (200 ng ml−1) at 37 °C for the indicated times. WCLs were subjected to immunoblotting with an anti-EGFR antibody. EGFR at each time point was quantified and indicated as a percentage relative to that at time zero (right panel; data are mean ± s.e.m., n = 3).",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(c) DQ-green BSA dequenching assay. Representative confocal microscopy images of DQ-BSA proteolysis (left panel) and flow cytometry analysis (right panel) of RAW264.7 cells expressing an empty vector (RAW264.7.Vec; dotted black line), wild-type UVRAG (red line) or UVRAGΔN(1-147) mutant (green line) loaded with 10 μg ml−1 DQ green-BSA for the indicated times. Background (grey line) represents samples without the BSA load.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(d) Effect of UVRAG on endosome fusion. RAW264.7.Vec and RAW264.7.UVRAG cells were pulse-labelled with Oregon green 514-avidin and dextran-568 for 10 min and chased for 30 min. Cells were then labelled with biotin-BSA for 10 min, and processed for confocal microscopy (left panel). In the absence of biotin-BSA, Oregon green514-avidin showed very low fluorescence (first row of confocal image). The percentage of dextran-568-labelled endosomes with visible Oregon green staining (denoted by arrows in the left panel) was calculated from approximately 20 different cells in 2 independent experiments (mean, right panel). Scale bars, 5 μm. The raw data of the immunoblots in b are shown in the Supplementary Information, Fig. S6.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "D.  SDH repression during acute phase of ENZA stress increased transcription of different AR-regulated genes without altering AR mRNAs levels in LNCaP cells. Data information: ENZA: enzalutamide.Data shown as mean ± SD of three independent experiments. Statistical analysis was performed using two tailed unpaired Student's t-test *, p<0.05 and **, p<0.01 compared between groups.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "E-F. Overexpression of SDHA and SDHB subunits decreased AR protein levels (E) and AR transactivation (F) in LNCaP cells. Data information: ENZA: enzalutamide.Data shown as mean ± SD of three independent experiments. Statistical analysis was performed using one-way ANOVA followed by Tukey's test *, p<0.05 and **, p<0.01 compared between groups.",
    "ncbi_link": "SDHA: 6389
SDHB: 6390"
  },
  {
    "caption": "C.  SDH-repressed LNCaP cells were able to maintain higher proliferation rate particularly during ENZA stress with or without Hsp27 silencing in real time cell proliferation assay. Data information: ENZA: enzalutamide. Data shown as mean ± SD of three independent experiments. Statistical analysis was performed using one-way ANOVA following Tukey's test for panels C (end points) . *, p<0.05, **, p<0.01 and ***, p<0.001 compared between groups",
    "ncbi_link": "Hsp27: 3315"
  },
  {
    "caption": "F.. Treatment with 5 µM STO-609 for 24 h in LNCaP cells inhibited AR upregulation induced by SDHA/SDHB subunit silencing.",
    "ncbi_link": "SDHA: 6389
SDHB: 6390"
  },
  {
    "caption": "(L) Histogram confirming the decreased number of Tuj1+ neurons in the ventral, but not dorsal, retina of Nr2f1 mutants. data are represented as mean ± SEM; N=3-4 Student t-test (*P<0.05, **P<0.01, ***P<0.001). Scale bars: 50µm.",
    "ncbi_link": "Nr2f1: 13865"
  },
  {
    "caption": "(A) GSCs contain the higher levels of stemness markers (Nestin, SOX2, Musashi-1, NANOG, and OCT4) compared with their DFCs. Total RNAs from GSCs and DFCs were subjected to real-time PCR. The average relative amounts of GSCs were normalized with those of DFCs. Shown are means +S.D. of the normalized mRNA levels of GSCs obtained from the three independent experiments.",
    "ncbi_link": "Musashi-1: 4440
NANOG: 79923
Nestin: 10763
OCT4: 5460
SOX2: 6657"
  },
  {
    "caption": "(A) Real-time PCR analysis of the proteasomal subunits PSMB5, PSMB6, and PSMB7 in XO8 GSCs and XO8 DFCs. Shown are means +S.D. values from the three independent experiments following normalization to those of GSCs. For statistical analysis, student t-test (two-sided, one type) were used. ** P value=PSMB5: 0.053, PSMB6: 0.034, PSMB7: 0.067. (B) Similar to (A) except that the cells were treated with 50 nM MG132 for 17 hrs. Shown are means +S.D. values from the three independent experiments following normalization to those of control cells treated with DMSO. For statistical analysis, student t-test (two-sided, one type) were used. ** P value=PSMB5: 0.022, PSMB6: 0.08, PSMB7: 0.603.",
    "ncbi_link": "PSMB5: 5693
PSMB6: 5694
PSMB7: 5695"
  },
  {
    "caption": "(E) XO8 cells were treated with 50 nM MG132 in the absence or presence of 5μM actinomycin D (ActD) for 6 h. The level of ATF3 mRNA was measured using semi-quantitative real-time PCR in comparison with β-actin.",
    "ncbi_link": "β-actin: 
ATF3: 467"
  },
  {
    "caption": "(A) HEK293 cells were transfected with ATF3 shRNA or vector (pLKO1), treated with 50 nM MG132, and then subjected to immunoblotting.",
    "ncbi_link": "ATF3: 467"
  },
  {
    "caption": "(B) Individualized XO8 GSCs were transduced with lentiviral shRNAs against ATF3 or control as described in Materials and Methods. After four days, individualized GSCs were treated with 50 nM MG132, and subjected to immunoblotting.",
    "ncbi_link": "ATF3: 467"
  },
  {
    "caption": "(C) XO8 GSCs were transfected with control or CHOP siRNA for 48 hrs and then treated with 50 nM MG132 for 24 hrs. Cell viability was determined using the Trypan blue exclusion assay. Error bars represent the mean ± SD from three independent experiments (*P < 0.05, n=3). For statistical analysis, student t-test (two-sided, one type) were used.",
    "ncbi_link": "CHOP: 1649"
  },
  {
    "caption": "(E) Wild-type and CHOP-/- MEF cells were treated with MG132 for 24 hrs. Cell viability was determined using trypan blue exclusion assay. Error bars represent the mean ± SD from three separate experiments (*P < 0.05, n=3). For statistical analysis, student t-test (two-sided, one type) were used.",
    "ncbi_link": "CHOP: 13198"
  },
  {
    "caption": "(G) The expression of NOXA was assessed with real-time PCR using total RNA extracted from XO8 GSCs treated with 50 nM MG132 alone or in combination with each inhibitor of ER stress-driven apoptosis (salubrinal; 15 µM, STK064652; 20 µM, STK047915; 20 µM). The mean +S.D. values from the three independent experiments are shown after normalization to that of control cells treated with DMSO. For statistical analysis, student t-test (two-sided, one type) was used. * P value: salubrinal, 0.0003; STK064650, 0.0036; STK047915, 0.0019.",
    "ncbi_link": "NOXA: 5366"
  },
  {
    "caption": "(B) Measurements of Tie2-pY992 staining intensity at intercellular junctions in aortic arch endothelial cells showing lower values in the inner curvature than in the upper curvature of VE-PTPfl/fl mice but equally high values in both regions of VE-PTPiECKO mice. Normalized to mean value for outer curvature of VE-PTPfl/fl mice scaled to 1.0. Mean ± SEM, n = 6 mice/group.",
    "ncbi_link": "VE-PTP: 19263"
  },
  {
    "caption": "(C) HUVEC transfected with control siRNA or VE-PTP siRNA and exposed to static or laminar shear force at 15 dyn/cm2 for 30 min, followed by immunoprecipitation of Tie2. Left. Blot showing immunoprecipitates (top) or cell lysates (bottom) immunoblotted for pan-phosphotyrosine (antibody 4G10), Tie2, or VE-PTP. Ratio of staining for phosphorylated Tie2 and total Tie2 (Tie2-pY to Tie2, n = 4 experiments). Right. Relative Tie2-pY levels in HUVEC after control siRNA or VE-PTP siRNA. Normalized to static control = 1.",
    "ncbi_link": "VE-PTP: 5787"
  },
  {
    "caption": "(D) Effect of shear stress on the phosphorylation levels of Tie2 Y992 at cellular junctions. HUVECs treated with either control siRNA (left) or Tie2 siRNA (right), were exposed to 15 dyn/cm2 shear stress for 5 min. The resulting cells were fixed and stained for Tie2-pY992 (red) and VE-cadherin (green).",
    "ncbi_link": "Tie2: 7010"
  },
  {
    "caption": "(E) HUVECs cultured on biotinylated gelatin were treated either with control siRNA, VE-PTP siRNA, Tie2 siRNA or VE-cadherin siRNA, then exposed to 15 dyn/cm2 shear stress for 30 minutes followed by 3 min incubation with Streptavidin-Alexa647 (red), washing, fixation and staining for VE-cadherin (green). (F and G) Quantification of Streptavidin leakage area per image. Mean ± SEM, n = 19 pooled in ten independent experiments (F), and n = 6 pooled in three independent experiments (G). D",
    "ncbi_link": "VE-cadherin: 1003
VE-PTP: 5787
Tie2: 7010"
  },
  {
    "caption": "(D-E) Fluorescence intensity distributions in D and mean intensities in E of extravasated anti-fibrinogen antibody in inner curvature of ApoE-/-/VE-PTPfl/fl mice and ApoE-/-/VE-PTPiECKO mice on high-fat diet for 7 wk. Mean ± SEM, n = 7 mice/group.",
    "ncbi_link": "ApoE: 11816
VE-PTP: 19263"
  },
  {
    "caption": "(C) The ~110KD fragment (asterisk) is related to AMOT. Wild-type (WT) and AMOT knockout (KO) HEK293A cells were treated with 10 μM proteasome inhibitor bortezomib (BTZ) for 6 h and subjected to Western blotting analysis using the indicated antibodies.",
    "ncbi_link": "AMOT: 154796"
  },
  {
    "caption": "(F) Deletion of DDI2 blocks AMOT cleavage. Wild-type (WT) and DDI2 KO cells were serum-starved overnight and then treated with 1 μM LPA for 2 h.",
    "ncbi_link": "DDI2: 84301"
  },
  {
    "caption": "(G) Both DDI1 and DDI2 mediate AMOT cleavage. Ectopically expressed FLAG-tagged DDI1 or DDI2 rescues AMOT cleavage in DDI2 KO HEK293A cells.",
    "ncbi_link": "FLAG: 
DDI1: 414301
DDI2: 84301"
  },
  {
    "caption": "K) The aspartic catalytic-site mutant DDI2 exhibits a dominant negative effect through inactivation of wild-type DDI2 in HEK293A cells. Wild-type HEK293A cells were transfected with the indicated plasmids and treated with 1 μM LPA (K) before harvest.",
    "ncbi_link": "DDI2: 84301"
  },
  {
    "caption": "(B and C) The TNKS1/2-RNF146 axis is crucial for AMOT cleavage. Wild-type (WT), TNKS1/2 double KO (dKO) and RNF146 KO HEK293A cells were treated with the proteasome inhibitor MG132 for 6 h before harvest. Cell lysates were subjected to Western blotting analysis using the indicated antibodies.",
    "ncbi_link": "RNF146: 81847
TNKS1: 8658"
  },
  {
    "caption": "(H and I) AMOT cleavage states in different cell lines with NF2-wild-type or NF2-deficiency.",
    "ncbi_link": "NF2: 4771"
  },
  {
    "caption": "(F RNF146 are indispensable for AMOT cleavage in HUVECs. siRNAs were transfected into HUVECs, the cells were treated with 10 μM BTZ for 6 h before harvest. Protein quantifications are shown below.",
    "ncbi_link": "RNF146: 81847"
  },
  {
    "caption": "(I and J) Quantification of the number of sprouts per spheroid and the cumulative sprout length of HUVECs. Vector (n=20), AMOT-WT (n=18), AMOT-ΔTBD (n=14), AMOT-Δcut (n=15), AMOTp80 (n=16), AMOT-NT (n=17) and AMOT-CT (n=21).",
    "ncbi_link": "AMOT: 154796"
  },
  {
    "caption": "(A and B) Knockdown of AMOT induces vascular development defects in zebrafish embryos. Lateral views of ISV and DLAV formation in Tg(flk:GFP) control and amot MO-injected zebrafish embryos at 30 h post-fertilization (hpf) are shown. Histogram depicts the quantification of normal and angiogenesis-defective embryos at 30 hpf (B). n: number of embryos analyzed. Dorsolateral anastomose vessels (DLAV), intersegmental vessels (ISV), dorsal aorta (DA) and posterior cardinal vein (PCV) are shown. Asterisks: defective ISV; dotted lines: dorsal edge of the embryo. Scale bar: 50 μm.",
    "ncbi_link": "GFP: 
AMOT: 563421
amot: 563421
flk: 796537"
  },
  {
    "caption": "(E and F) Non-cleavable AMOT mutant fails to support angiogenesis. Embryos were injected with amot MO together with mRNA encoding wild-type (WT) or mutant (ΔTBD, NT, CT, and Δcut) AMOT. Scale bar: 50 μm.",
    "ncbi_link": "amot: 563421
AMOT: 154796"
  },
  {
    "caption": "(G and H) AMOT-CT but not full-length AMOT could rescue impaired angiogenesis in ddi2-deficient embryos. Embryos were injected with ddi2 MO together with mRNA encoding wild-type AMOT (AMOT-WT) or AMOT-CT. Scale bar: 50 μm. (I and J) Nelfinavir (NFV) and XAV939 repress ISV development. Embryos were treated with 5 μM NFV, 10 μM XAV939 at 6 hpf for 24 h. Number of ISV defects was counted at 30 hpf. Scale bar: 50 μm.",
    "ncbi_link": "AMOT: 154796
ddi2: 386644"
  },
  {
    "caption": "(D) Ddi2iEC-KO mice show delayed retinal angiogenesis. Immunofluorescent images of whole-mount retinas stained for IB4 and ERG of control, Ddi2iEC-KO and Ddi2iEC-KO; CTiEC-TG mice at P6. White dash rectangles indicate regions of interest (ROI) are shown below at higher magnification. Scale bar: 100 μm.",
    "ncbi_link": "Ddi2: 68817"
  },
  {
    "caption": "(F) High magnification confocal images of filopodia extension at the leading edge of the P6 retina. Tip cells are labeled with IB4. Scale bar: 10 μm. (G) Quantification of the number and average length of filopodia in control (n=8), Ddi2iEC-KO (n=9) and Ddi2iEC-KO; CTiEC-TG (n=8) P6 retinal sprouts. Each data point represents the average of three measurements from one retina.",
    "ncbi_link": "Ddi2: 68817"
  },
  {
    "caption": "(H and I) Representative images and comparisons of Ki67 positive endothelial cells in control (n=8), Ddi2iEC-KO (n=8) and Ddi2iEC-KO; CTiEC-TG (n=7) P6 retinas. Each data point represents the average of three measurements from one retina. Scale bar: 50 μm.",
    "ncbi_link": "Ddi2: 68817"
  },
  {
    "caption": "(D) Nf2iEC-KO retinas show endothelial cell accumulation in the sprouting front and sparse vascular plexus in the region close to optic stalk. CT overexpression can partially rescue the phenotype. Immunofluorescent images of whole-mount P6 retinas stained for IB4 and ERG are shown. White rectangles indicate regions of interest (ROI). Scale bar: 100 μm.",
    "ncbi_link": "Nf2: 18016"
  },
  {
    "caption": "(F and G) High magnification confocal images and quantification of filopodia extension at the leading edge of the P6 retinas. Tip cells are labeled with IB4. Scale bar: 10 μm. Control (n=10), Nf2iEC-KO (n=10), Nf2iEC-KO; CTiEC-TG (n=10) and Nf2iEC-KO; ΔcutiEC-TG (n=8).",
    "ncbi_link": "Nf2: 18016"
  },
  {
    "caption": "(H and I) Representative images and comparisons of Ki67 positive endothelial cells in control (n=8), Nf2iEC-KO (n=8), Nf2iEC-KO; CTiEC-TG (n=8) and Nf2iEC-KO; ΔcutiEC-TG (n=7) P6 retinas. Each data point represents the average of three measurements from one retina. Scale bar: 50 μm.",
    "ncbi_link": "Nf2: 18016"
  },
  {
    "caption": "(D) Blocking AMOT cleavage inhibits revascularization in the OIR model. Upper, IB4 staining of the whole retina of P17 WT and Δcut KI mice after OIR. Lower, higher magnification images of sprouting vessels from veins. Scale bars are shown in the figures.",
    "ncbi_link": "AMOT: 27494"
  },
  {
    "caption": "Cell count of Ronin fl/del and Ronin del/del ESC. Data represent mean ± SD, n = three independent experiments.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Annexin V cell death assay of Ronin fl/del and Ronin del/del cultured for 6 days. Two-tailed unpaired Student's t test, data represent mean ± SD, n = three independent experiments.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Ronin fl/del and Ronin del/del ESC stained for Ronin (left panel) or Oct4 (right panel). The nuclei are counterstained with DAPI.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Haematoxylin/eosin staining of paraffin sections of Ronin fl/del and ecto-Ronin teratomas.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "In vitro differentiation of Ronin fl/del, ecto-Ronin (grown in the presence of Dox) and Ronin del/del ESC.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Volcano plot of gene expression in Ronin del/del day 4 vs. Ronin fl/del (left panel) and Ronin del/del day 8 vs. Ronin fl/del ESC (right panel) with annotated naïve and primed pluripotency markers.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Volcano plot of gene expression in Ronin del/del day 8 vs. Ronin del/del day 4 ESC.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Analysis of nascent protein synthesis using OP-puro assay. Ronin fl/del cells treated with protein synthesis inhibitor (cycloheximide) are used as negative control. The nuclei are counterstained with DAPI.   Quantification of the OP-puro signal, normalised to DAPI. Ordinary one-way Anova data represent mean ± SD; n = three independent experiments for each genotype.   ",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "Transmission electron microscopy analysis of mitochondrial structure in Ronin fl/del and Ronin del/del ESC. Mitochondria analysed, n > 150 for each condition.",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "E4.5 chimeric embryos stained for tdTomato and DAPI.   Quantification of donor cells' contribution in E4.5 blastocysts, Mann-Whitney test, data represent mean ± SD; Ronin fl/del n embryos = 26, Ronin del/del n embryos = 27.   Diapause embryos stained for tdTomato and DAPI.   Quantification of donor cells' contribution in diapause embryos, unpaired Student's t test, data represent mean ± SD, Ronin fl/del n embryos = 4, Ronin del/del n embryos = 12.   E5.5 chimeric embryos stained for tdTomato and DAPI.   Quantification of donor cells' contribution in E5.5 embryos, unpaired Student's t test, data represent mean ± SD, Ronin fl/del n embryos = 21, Ronin del/del n embryos = 15.   Reactivated E5.5 chimeric embryos stained for tdTomato and DAPI.   Quantification of donor cells' contribution in reactivated E5.5 embryos, Mann-Whitney test, data represent mean ± SD, Ronin fl/del n embryos = 17, Ronin del/del n embryos = 12.   ",
    "ncbi_link": "Ronin: 59016"
  },
  {
    "caption": "A Immunoblot analysis of the knockdown of exogenous USP19 in 293T cells expressing Flag-USP19 (top) or endogenous USP19 in HeLa cells (bottom) treated with USP19-specific siRNA or scrambled (Scr) siRNA.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "B Representative images of GFP-LC3B puncta in HeLa-GFP-LC3B cells transfected with USP19-specific siRNA or scrambled siRNA during growth in normal medium (DMEM) or EBSS medium for 3 h. Arrows denote representative autophagosomes. Scale bar, 200 μm.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "C Quantification of GFP-LC3B puncta in HeLa-GFP-LC3B cells transfected with USP19-specific siRNA or scrambled siRNA. Bars represented mean ± standard error of the mean (SEM) of triplicate samples (20 cells per sample). *p < 0.05, **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "D Immunoblot detection of the relative accumulation of LC3 I and LC3 II in HeLa cells transfected with USP19-specific siRNA or scrambled siRNA with rapamycin (250 nM) treatment for 12 h.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "E HeLa cells were transfected with USP19-specific siRNA or scrambled siRNA and treated with indicated concentration of rapamycin for 12 h, p62 levels were detected by immunoblot.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "F Human peripheral blood mononuclear cells (PBMCs) transfected with control or USP19-specific siRNA were treated with rapamycin (250 nM) for 18 h, the lysates were analyzed with each antibody.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "H Flag-USP19 inducible HeLa cells were treated with 200 ng/ml doxycycline (Doxy) for overnight to induce the expression of Flag-USP19. The protein levels of p62 were analyzed after rapamycin treatment for 12 h at indicated concentrations.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "I GFP-LC3B stably expressing HeLa cells were transfected with pcDNA3.1 empty vector or plasmid expressing the wild-type and the mutant forms of USP19 (CS or CS/HA). Pictures in (B) and (I) were taken using Leica DMI3000 B microscope with a×100 oil-immersion objective. Scale bar, 200 μm.J Average GFP-LC3B puncta per cell were calculated. Bars represented mean ± SEM of triplicate samples (20 cells per sample). *p < 0.05, **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "A 293T cells were transfected with plasmids encoding HA-USP19 and Flag-tagged Beclin-1 complex members (Flag-ATG14L, Flag-VPS15, Flag-Beclin-1, Flag-VPS34, Flag-UVRAG and Flag-AMBRA1), followed by immunoprecipitation (IP) with anti-Flag beads and immunoblot analysis with anti-HA. Throughout was the immunoblot analysis of whole-cell lysates (WCL) without immunoprecipitation.",
    "ncbi_link": "AMBRA1: 55626
ATG14L: 22863
Beclin-1: 8678
VPS34: 5289
VPS15: 30849
UVRAG: 7405"
  },
  {
    "caption": "B, C Extracts of A549 cells (B) or human PBMCs (C) incubated with EBSS for various time points (above lanes) were subjected to immunoprecipitation with anti-Beclin-1 and immunoblot analysis with indicated antibodies (shown on the left).",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "F Co-immunoprecipitation and immunoblot analysis of 293T cells transfected with deletion mutants of USP19 plasmid along with vector encoding Flag-Beclin-1.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "G Co-immunoprecipitation and immunoblot analysis of 293T cells transfected with deletion mutants of Beclin-1 plasmid along with vector encoding HA-USP19.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "C BECN1 mRNA levels of the same sample (B) were detected by real-time PCR. Bars represented mean ± SEM of triplicate samples.",
    "ncbi_link": "BECN1: 8678"
  },
  {
    "caption": "D Human PBMCs were transfected with USP19-specific or scramble siRNA and treated with rapamycin (250 nM) for 18 h. The extracts were analyzed by immunoblot with indicated antibodies.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "E Wild-type (WT) and USP19 KO A549 cells were cultured in EBSS for indicated time points, and the protein expression levels of Beclin-1 and ULK1 were detected by immunoblot.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "F USP13 KO HEK293T cells were transfected with plasmids encoding Myc-USP5, Myc-USP19 and Myc-USP38 and the cellular extracts were analyzed by immunoblot.",
    "ncbi_link": "USP13: 8975
USP19: 10869
USP38: 84640
USP5: 8078"
  },
  {
    "caption": "G 293T cells transfected with plasmid expressing Flag-Beclin-1 and empty vector or Myc-tagged USP19 (WT, CS, CS/HA or ΔTMD), the lysates were analyzed by immunoblot.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "H 293T cells were transfected with plasmid encoding Flag-Beclin-1 and treated with CHX (100 μg/ml) alone or with MG132 (10 μM), 3MA (10 mM), CQ (50 μM) as combination for 6 h or transfected with the HA-USP19 plasmid. The cell lysates were analyzed by immunoblot.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "A HeLa cells were transfected with USP19 siRNA or scrambled siRNA and protein extracts were harvested after MG132 (10 μM) treatment for 3 h. Protein extracts were immunoprecipitated using anti-Beclin-1 antibody or with IgG as a negative control and analyzed by immunoblot using anti-ubiquitin and anti-Beclin-1 antibodies.",
    "ncbi_link": "Beclin-1: 8678
USP19: 10869"
  },
  {
    "caption": "B Lysates of 293T cells transfected with plasmid expressing Flag-Beclin-1 and HA-tagged ubiquitin (HA-Ub (wild type), K6-linked-Ub, K11-linked-Ub, K27-linked-Ub, K29-linked-Ub, K33-linked-Ub, K48-linked-Ub or K63-linked-Ub), together with the empty vector or expression vector of Myc-USP19 and treated with MG132 (10 μM) for 3 h were immunoprecipitated with anti-Flag and immunoblotted with anti-HA.",
    "ncbi_link": "ubiquitin: 7311///6233///7316///7314
USP19: 10869"
  },
  {
    "caption": "C HeLa cells were transfected with USP19-specific siRNA and plasmid encoding Flag-Beclin-1, plus K11-linked-Ub. Protein was harvested after MG132 (10 μM) treatment for 3 h and immunoprecipitated with anti-Flag and immunoblotted with anti-HA.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "D 293T cells were transfected with plasmid for Flag-Beclin-1 and HA-K11-Ub, together with the empty vector or expression vector for Myc-USP19 (WT, CS or CS/HA) and treated with MG132 (10 μM). Cell lysates were subjected to immunoprecipitation with anti-Flag and immunoblot analysis with anti-HA.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "E Purified ubiquitinated Beclin-1 was incubated with immunopurified Flag-USP19 in vitro in deubiquitinating buffer. The immunoblot was probed with anti-HA.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "A Lysates of 293T cells transfected with plasmid for Flag-Beclin-1 and HA-K11-linked-Ub, together with empty vector or expression vector for Myc-USP5 or Myc-USP19 were immunoprecipitated with anti-Flag and immunoblotted with anti-HA.",
    "ncbi_link": "USP19: 10869
USP5: 8078"
  },
  {
    "caption": "B Immunoprecipitation and immunoblot analysis of 293T cells transfected with vectors expressing Flag-Beclin-1 and HA-K11-linked ubiquitin.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "C 293T cells were transfected with Flag-Beclin-1 (WT or K437R) and treated with CHX (100 μg/ml) for indicated time points. The expression levels of WT and K437R Flag-Beclin-1 were analyzed by immunoblot.D Quantification of the expression levels of WT and K437R Flag-Beclin-1.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "E Immunoblot analysis of protein extracts of 293T cells transfected with empty vector or vector for HA-USP19, together with plasmid expressing WT or K427R, K430R or K437R mutant of Flag-Beclin-1.",
    "ncbi_link": "Beclin-1: 8678
USP19: 10869"
  },
  {
    "caption": "F HeLa cells transfected with BECN1 sgRNA and restored with WT and K437R Flag-Beclin-1 were stained by anti-LC3 antibody. Scale bar, 200 μm.G Quantification of LC3 puncta shown in (F). Bars represented mean ± SEM of triplicate samples. *p < 0.05, **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "Beclin-1: 8678
BECN1: 8678"
  },
  {
    "caption": "A Luciferase activity in 293T cells transfected with an ISRE (left) or IFN-β (right) promoter-driven luciferase reporter and together with plasmid encoding RIG-I (N) or cGAS and STING.",
    "ncbi_link": "Luciferase: 
luciferase: 
IFN-β: 3456"
  },
  {
    "caption": "B Protein lysates of WT and USP19 KO A549 cells infected with SeV at indicated time points were immunoblotted with indicated antibodies.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "C RT-PCR analysis of gene transcription in WT and USP19 KO A549 cells after infection with SeV at indicated time points.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "D Phase-contrast microscopy (PH) and fluorescence microscopy images of WT and USP19 KO A549 cells infected with VSV-eGFP at an MOI of 0.01 for the indicated time length. Scale bar, 50 μm.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "E Human PBMCs were transfected with control or USP19-specific siRNA, followed by treatment with influenza A/Puerto Rico/8/34 (H1N1) (PR8) (MOI = 5) at different time points, the lysates were analyzed with each antibody.",
    "ncbi_link": "USP19: 10869"
  },
  {
    "caption": "F Human PBMCs were transfected with control or USP19-specific siRNA were infected with H1N1 virus (MOI = 5) at different time points. Relative expression levels of IFNB, ISG15, ISG54, ISG56 mRNA and H1N1 nucleoprotein (NP) RNA were measured by real-time PCR.",
    "ncbi_link": "ISG56: 3434
ISG54: 3433
IFNB: 3456
ISG15: 9636
NP: 956531
nucleoprotein: 956531
USP19: 10869"
  },
  {
    "caption": "G Relative expression levels of IFNB mRNA and interferon-stimulated genes, including ISG54 and ISG56 in WT, BECN1, ATG5 and SQSTM1 KO cells with or without USP19.",
    "ncbi_link": "ATG5: 9474
BECN1: 8678
ISG56: 3434
ISG54: 3433
IFNB: 3456
SQSTM1: 8878
USP19: 10869"
  },
  {
    "caption": "H, I Luciferase activity in WT and BECN1 KO 293T cells transfected with an ISRE (H) or IFN-β (I) promoter-driven luciferase reporter after infection with SeV for indicated time points.",
    "ncbi_link": "Luciferase: 
luciferase: 
BECN1: 8678
IFN-β: 3456"
  },
  {
    "caption": "A Luciferase activity in WT and BECN1 KO 293T cells transfected with an ISRE (left) or IFN-β (right) promoter-driven luciferase reporter after infection with SeV for 12 h.",
    "ncbi_link": "Luciferase: 
luciferase: 
BECN1: 8678
IFN-β: 3456"
  },
  {
    "caption": "B WT and BECN1 KO 293T cells were infected with SeV for indicated time points, then protein extracts were analyzed by immunoblot using the indicated antibodies.",
    "ncbi_link": "BECN1: 8678"
  },
  {
    "caption": "C Protein extracts of THP-1 cells infected with SeV for various time points (upper lanes) were subjected to immunoprecipitation with anti-Beclin-1 and immunoblot analysis with antibodies shown on the left.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "E 293T cells were transfected with vectors encoding HA-Beclin-1 and Flag-MAVS or Flag-MAVSΔCARD, followed by IP with anti-Flag beads and immunoblot analysis with anti-HA.",
    "ncbi_link": "MAVS: 57506"
  },
  {
    "caption": "F Co-immunoprecipitation and immunoblot analysis of WT and BECN1 KO 293T cells transfected with HA-MAVS plasmid along with vector encoding Flag-RIG-I (N) in the absence or presence of USP19.",
    "ncbi_link": "BECN1: 8678
RIG-I: 23586
USP19: 10869"
  },
  {
    "caption": "G Protein extracts of scramble or USP19-specific siRNA treated 293T cells transfected with HA-MAVS plasmid along with vector encoding for Flag-RIG-I (N) in the absence or presence of Beclin-1 were subjected to immunoprecipitation and immunoblot analysis.",
    "ncbi_link": "Beclin-1: 8678
RIG-I: 23586
USP19: 10869"
  },
  {
    "caption": "H Luciferase activity in 293T cells transfected with scramble or USP19-specific siRNA and ISRE luciferase reporter after SeV infection for indicated time points with or without Beclin-1.",
    "ncbi_link": "Luciferase: 
luciferase: 
Beclin-1: 8678
USP19: 10869"
  },
  {
    "caption": "I Luciferase activity in 293T cells transfected with scramble or USP19-specific siRNA and IFN-β luciferase reporter after SeV infection for indicated time points with or without Beclin-1.",
    "ncbi_link": "Luciferase: 
luciferase: 
Beclin-1: 8678
IFN-β: 3456
USP19: 10869"
  },
  {
    "caption": "A, B Immunofluorescence  of PAR-3  (A) and proportions of mESC  clusters with a strong PAR-3 centre (B) in wild-type (W4) and E-cadherin  knock-out (Cdh1  KO) mESCs  at 24 hrs in Matrigel. Data information: Data are presented as means ± SEM in (B) n = 3 experiments in (B) Two-way ANOVA analysis in (B), P values were listed in the graphs. scale bars: 10 µm.",
    "ncbi_link": "Cdh1: 12550
E-cadherin: 12550"
  },
  {
    "caption": "C Line-scan profiles of PAR-3   at the cell-cell interface in wild-type control, mitomycin C  treated and Cdh1  KO control, mitomycin C treated 2-cell doublets. D Ratio of  PAR-3  pixel intensity values at central and surrounding regions in >2-cell mESC  clusters. Data information: individual and mean-valued line-scans in (C) individual cell cluster values (small dots), mean experimental values (large dots) and means of 3 experiments (bars) ± SEM in (D) 17-50 cell clusters were analysed for each column in every experiment; 15 doublets for each condition in (C); 17-30 cell clusters were analysed for each condition in every experiment in (D); Two-way ANOVA analysis in (D), P values were listed in the graphs. scale bars: 10 µm.",
    "ncbi_link": "Cdh1: 12550"
  },
  {
    "caption": "E, F Representative images of  PAR-3 immunofluorescence  (E) and line-scan profiles of PAR-3 at the cell-cell interface (F) in WT homogeneous or WT (ES-E14) /Cdh1  KO chimeric mESC  2-cell doublets. *, WT mESCs. Data information: individual and mean-valued line-scans in (F); 15 doublets for each condition in (F)",
    "ncbi_link": "Cdh1: 12550"
  },
  {
    "caption": "G, H Representative images of ZO-1 puncta and Golgi apparatus  (G) and proportions of mESC  doublets with central ZO-1 puncta or polarised Golgi apparatus  (H) in WT and Cdh1  KO mESC  doublets. Data information: Data are presented as means ± SEM in (H); student's t-test analysis in (H); P values were listed in the graphs. scale bars: 10 µm.",
    "ncbi_link": "Cdh1: 12550"
  },
  {
    "caption": "A-C Immunofluorescence of PAR-3 and P-cadherin (A), proportions of mESC   clusters with a positive PAR-3  centre (B) and line-scans of PAR-3 at the cell-cell interface (C) in control, P-cadherin  knock-down by RNAi, mitomycin  treated and P-cadherin knock-down mitomycin  treated W4 mESC  doublets cultured for 24 hours in Matrigel. Data information: Data are presented as means ± SEM in (B) ; individual and mean-valued line-scans in (C) n = 3 experiments in (B), 15-21 clusters were analysed for each column in every experiment; 15-21 line-scans in (C) Two-way ANOVA analysis in (B) P values were listed in the graphs. scale bars: 5 µm.",
    "ncbi_link": "P-cadherin: 12560"
  },
  {
    "caption": "D-F Immunofluorescence  of PAR-3  and JAM-A (D), proportions of mESC  clusters with a positive PAR-3 centre (E) and line-scans of PAR-3 at the cell-cell interface (F) in control, JAM-A knock-down by RNAi, mitomycin  treated and JAM-A knock-down mitomycin  treated W4 mESC  doublets cultured for 24 hours in Matrigel. Data information: Data are presented as means ± SEM in (E), individual and mean-valued line-scans in (F) n = 3 experiments in (E), 15-21 clusters were analysed for each column in every experiment; 15-21 line-scans in (F), Two-way ANOVA analysis in (E), P values were listed in the graphs. scale bars: 5 µm.",
    "ncbi_link": "JAM-A: 16456"
  },
  {
    "caption": "G-I Immunofluorescence  of PAR-3 and Nectin-2 (G), proportions of mESC  clusters with a positive PAR-3 centre (H) and line-scans of PAR-3  at the cell-cell interface (I) in control, Nectin-2 knock-down by RNAi, mitomycin  treated and Nectin-2  knock-down mitomycin  treated W4 mESC  doublets cultured for 24 hours in Matrigel. Data information: Data are presented as means ± SEM in (H); individual and mean-valued line-scans in (I). n = 3 experiments in (H), 15-21 clusters were analysed for each column in every experiment; 15-21 line-scans in (I). Two-way ANOVA analysis in (H); P values were listed in the graphs. scale bars: 5 µm.",
    "ncbi_link": "Nectin-2: 19294"
  },
  {
    "caption": "A, B Immunofluorescence  of PAR-3 (A) and proportions of mESC  doublets with polarised  PAR-3 (B) in wild-type (ES-E14) and E-cadherin knock-out (Cdh1  KO) cells at 30 hours in 0.5% agarose. Data information: Data are presented as means ± SEM in (B); n = 3 experiments in (B) Two-way ANOVA analysis in (B) P values were listed in the graphs. scale bars: 5 µm.",
    "ncbi_link": "Cdh1: 12550
E-cadherin: 12550"
  },
  {
    "caption": "D Percentage of cell clusters with different cavities relative to total cell clusters at different  time points. The analysis was compared between the closed/rosette category among the conditions. E Percentage of cell clusters with closed cavities relative to total cell clusters with cavities calculated from (D). Data information: Data are presented as means ± SEM in (D) & (E). n = 20 (48 hours WT & Cdh1  KO), 30 (72 hours WT) and 32 (72 hours Cdh1  KO) images in (A); 3 experiments in (D) & (E), at least 25 clusters were analysed for each column in every experiment. Two-way ANOVA analysis in (D) & (E); P values were listed in the graphs.",
    "ncbi_link": "Cdh1: 12550"
  },
  {
    "caption": "Human  first-trimester trophoblast cell line Sw.71 (left panel) and human primary culture (right panel) trophoblast  cells were infected with ZIKV  (MOI=2) for 1 h and refreshed with regular media over  time. RNA was collected for measuring gene expression by qRT-PCR. Data represent as mean ± SEM; n=4 biological replicates. NT, no treatment group; HPC, human primary culture. (B) IFNα  is not highly induced in response to ZIKV  infection in trophoblast cells.  IFNα mRNA expression was inhibited in the first 24 h.p.i. and maintained at low level during  ZIKV infection. Difference not significant (n.s.) by One-way ANOVA.",
    "ncbi_link": "IFNα: 3439"
  },
  {
    "caption": "Human first-trimester trophoblast  cell line Sw.71 (left panel) and human primary culture  (right panel) trophoblast  cells were infected with ZIKV  (MOI=2) for 1 h and refreshed with regular media over  time. RNA was collected for measuring gene expression  by qRT-PCR. Data represent as mean ± SEM; n=4 biological replicates. NT, no treatment group; HPC, human primary culture. (C) ZIKV infection induced a  time-dependent increase in IFNβ mRNA expression in Sw.71  and HPC. *p < 0.05, **p < 0.01 by One-way ANOVA.",
    "ncbi_link": "IFNβ: 3456"
  },
  {
    "caption": "Sw.71 (left panel) and HPC cells (right panel) were treated with  IFNβ to detect ISG20 mRNA expression. Data represent as mean ± SEM; n=3 biological replicates. NT, no treatment group; HPC, human primary culture. (A) Sw.71 and HPC cells were treated with different  doses of IFNβ (3, 30, 300 ng/ml) for 8 h and RNA were collected for determining ISG20 mRNA expressions  by qRT-PCR. Note the increase of ISG20 mRNA expression in a dose-dependent manner. *p < 0.05, **p < 0.01 by One-way ANOVA. (B) Sw.71  and HPC cells were treated with 300ng/ml IFNβ over  time and RNA was collected for determining ISG20 mRNA expressions by qRT-PCR. Note the increase of ISG20 mRNA expression in a time-dependent manner. *p < 0.05 by One-way ANOVA. (C) ",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(B) No  ISG20 protein expression in ISG20-/- Sw.71  in ZIKV infection. Sw.71 and ISG20-/- Sw.71 cells were infected with  ZIKV  (MOI=2) for 1 h and refreshed with regular media for 48 h, and proteins were collected for western blot  analysis.  β-actin served as a loading control.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(C) Higher  ZIKA titer was shown in ISG20-/- Sw.71 cells. Sw.71 and  ISG20-/- Sw.71 cells were infected with ZIKV  (MOI=2) for 1 h and refreshed with regular media for 48 h, and  RNA  was collected for determining the viral titer and gene expression by qRT-PCR. Data represent as mean ± SEM; n=4 biological replicates; *p < 0.05 by Student's t-test.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(D) More viral shedding in  ZIKV-infected  ISG20-/- Sw.71  cell culture supernatant. Supernatant from ZIKV-infected Sw.71  and  ISG20-/- Sw.71 cells were collected and plaque assay was performed using Vero  cells. A representative  plaque assay picture is presented. Note that more plaques were formed in Vero  cells by incubating with ZIKV-infected ISG20-/- Sw.71  cell culture supernatant. Scale bar=130μm. (E) Plaques were counted and  plaque forming-unit (pfu) ratio was calculated for the comparison of the viral titers. Data represent as mean ± SEM; n=3 biological replicates. *p < 0.05 by Student's t-test. ",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(B) ISGs mRNA expression stimulated by IFNβ  in Sw.71 and ISG20-/- Sw.71 trophoblast cells. Sw.71 and ISG20-/- Sw.71 cells were treated with 30 ng/ml IFNβ for 24 h, and RNA was collected for determining the ISGs gene expression  by qRT-PCR. Data represent as mean ± SEM; n=3 biological replicates; *p < 0.05, **p < 0.01 by Student's t-test against control.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(D)  IFNβ pre-treatment significantly prevented trophoblast  cells from ZIKV infection, however, this protection was evidently attenuated due to lack of ISG20. Sw.71 and ISG20-/- Sw.71  cells were pre-treated with or without 30 ng/ml IFNβ for 24 h, followed by ZIKV infection (MOI=2) for 1 h and refreshed with regular media for 24 h, and  RNA was collected to determine the viral titers by qRT-PCR. Data represent as mean ± SEM; n=4 biological replicates; *p < 0.05 by Student's t-test.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "(D) ISG20 secretion in the positive clone supernatant significantly decreased ZIKV infection in  trophoblast  cells. Supernatants from negative and positive clones were collected and added to ISG20-/- Sw.71 trophoblast  cells together with ZIKA  virus (MOI=2) for 1 h, followed by refreshing with new growth media for 48 h.  RNA was then collected to determine viral titers by qRT-PCR. Data represent as mean ± SEM; n=3 biological replicates; **p < 0.01 by Student's t-test.",
    "ncbi_link": "ISG20: 3669"
  },
  {
    "caption": "A In apoptotic Drp1 knockdown U2OS cells, cytochrome c release is delayed. Confocal overview image of an apoptotic Drp1 knockdown cell labelled with antibodies against Tom20 (red), cytochrome c (blue) and Bax (green). Large image: Overlay of all three channels. Small images: Magnifications of the area indicated by the rectangle in the large image. Shown are the individual channels, as indicated. The arrows point to mitochondria that had not released cytochrome c; the asterisks denote mitochondria that had released cytochrome c. Scale bars: 10 µm (overview) and 2 µm (magnifications).",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "B In Drp1 knockdown cells Bax-ring formation and cytochrome c release is not correlated. Three-color images of apoptotic mitochondria of Drp1 knockdown cells. From left to right: Tom22, Bax (recorded in the STED-mode), cytochrome c and an overlay of all three channels. The arrows point to Bax-rings. Scale bar: 1 µm.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "Drp1 knockdown cells were treated with DMSO (control) or with actinomycin D for 14 h to induce apoptosis and were decorated with antisera against Bax, cytochrome c, and Mic27 or Mic60 (see Appendix Figure S4). Three-color images were taken, whereby Mic27 or Mic60 were recorded in the STED mode. Relying on the Bax and the cytochrome c signals, we discriminated between healthy and apoptotic mitochondria before and after cytochrome c release. The distributions of Mic27 or Mic60 were analyzed by determining the normalized variance of the fluorescence intensity, which is a sensitive measure for the distribution of the labelled protein. The numbers within the columns represent the numbers of images analyzed and the error bars represent the standard error of the mean.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "D Relative change in the growth rates of E. coli K-12 BW25113 Δpgi and ΔpfkA strains in the presence of 10 mM acetate. Mean values ± standard deviations (error bars) were estimated from three independent biological replicates.",
    "ncbi_link": "pfkA: 948412
pgi: 948535"
  },
  {
    "caption": "Relative change in the growth rates of wild-type, Δpta, and Δacs E. coli K-12 BW25113 strains in the presence of 10 mM acetate at low glycolytic flux (100 mM αMG). Mean values and standard deviations (error bars) were estimated from n independent biological replicates, as indicated on the figure.",
    "ncbi_link": "acs: 948572
pta: 946778"
  },
  {
    "caption": "A,B Impact of the presence of 10 mM acetate on the growth rate of wild-type, Δpta, and Δacs E. coli K-12 BW25113 strains grown on (A) 30 mM glycerol and (B) 15 mM galactose. Mean values and standard deviations (error bars) were estimated from three independent biological replicates.",
    "ncbi_link": "acs: 948572
pta: 946778"
  },
  {
    "caption": "Immunoblot analysis of proteins biotinylated  and isolated as in (A). Parental HeLa-T-REx cells or cells expressing H3.1-BirA*-HA and treated with biotin for indicated times.",
    "ncbi_link": "HA: 
BirA: 948469
H3.1: 8350"
  },
  {
    "caption": "Immunoblot  analysis of TAP-H3.1 or -CENP-A pulldown of UBR7-LAP (schematic, upper).  293T cells were co-transfected with UBR7-LAP and TAP-tagged constructs, which were purified on IgG-conjugated sepharose beads.",
    "ncbi_link": "LAP: 
TAP: 
UBR7: 55148"
  },
  {
    "caption": "Representative images of HeLa  cells transfected with UBR7-FL. DNA is visualized via  DAPI staining shown in magenta and immunofluorescence for 3xFLAG is shown in green. The area within yellow dotted box in (E) is magnified 4x in (E'). Scale bar = 5 μm.   Quantification of the nuclear anti-FLAG immunofluorescence  intensity in (E). Error bars represent mean +/- standard deviation. One way ANOVA was used to calculate p-values (italics) associated with differences between treatments. Experiment in (E-F) was performed twice.  ",
    "ncbi_link": "FL: 
UBR7: 55148"
  },
  {
    "caption": "Immunoblot  analysis of anti-H3.1-HA pulldown of full-length UBR7-LAP and UBR7PHD fragment (residues 117-215) (schematic, upper). 293T cells were transfected as in (A). Values below pulldown  represent H3.1-HA-normalized GFP-UBR7 immunoblot signal relative to UBR7-FL. Data were acquired from a continuous membrane, and the image is cropped to omit irrelevant samples. Numbers below  blot  indicate HA-normalized anti-GFP immunoblot  signal relative to full length UBR7-LAP.",
    "ncbi_link": "LAP: 
UBR7: 55148"
  },
  {
    "caption": "Anti-GFP immunoblot analysis of streptavidin pulldown of the indicated biotin-conjugated H3  peptides following incubation with 293T-GFP-UBR7 cell lysate after mutation of residues highlighted in (C).",
    "ncbi_link": "GFP: 
UBR7: 55148"
  },
  {
    "caption": "Immunoblot  analysis for total and modified histones in anti-FLAG pulldown of constructs from soluble cellular fractions demonstrates that UBR7 UBR box and PHD are necessary for binding to post-nucleosomal H3/H4.",
    "ncbi_link": "UBR7: 55148"
  },
  {
    "caption": "Representative images of HeLa cells transfected with sNASP-FL. DNA is visualized via DAPI staining shown in magenta and immunofluorescence for 3xFLAG is shown in green. Scale bar = 5 μm.   Quantification of the nuclear anti-FLAG immunofluorescence intensity in (G) demonstrating that  sNASP-FL is highly susceptible to pre-extraction with Triton X-100. One way ANOVA was used to determine p-values (italics) associated with differences between treatments. Error bars represent mean +/- standard deviation. Experiment in (G-H) was performed twice.  ",
    "ncbi_link": "FL: 
sNASP: 4678"
  },
  {
    "caption": "Immunoblot analysis of H3, UBR7, and GAPDH in the non-nucleosomal fraction of parental and 293T-UBR7KO cells.   Quantification of anti-H3 immunoblot represented in (A). Immunoblot signals were normalized to anti-GAPDH signal. Error bars represent mean +/- standard deviation. A two-tailed one-sample t-test was used to calculate p-value (italics) associated with group mean difference from a hypothetical value of 1.0 (represented by dashed line). Experiment in (A-B) was performed in three times.  ",
    "ncbi_link": "UBR7: 55148"
  },
  {
    "caption": "Immunoblot analysis of anti-FLAG pulldown of sNASP-FL in parental or  293T-UBR7KO cells. 3xFLAG tagged sNASP-FL was immunoprecipitated  from non-nucleosomal fraction and eluted with FLAG peptide. Experiment was performed three times.   Quantification of anti-FLAG (sNASP-FL), and anti-histone  immunoblots represented in (C). Immunoblot  signals were normalized to anti-FLAG signal. Error bars represent mean +/- standard deviation. A two-tailed one sample t-test was used to calculate p-values (italics) associated with group means difference from a hypothetical value of 1.0 (represented by dashed line). Experiments were performed two (sNASP,  H4) to three (all other targets) times.  ",
    "ncbi_link": "UBR7: 55148"
  },
  {
    "caption": "Immunoblot for LAMP2A in parental 293T cells or cells expressing   UBR7-FL (left) or  sNASP-FL (right) following treatment with siCTRL, siLAMP2A, or MG-132.",
    "ncbi_link": "FL: 
LAMP2A: 3920
sNASP: 4678
UBR7: 55148"
  },
  {
    "caption": "Heatmaps of ATAC-seq, anti-GFP (GFP-UBR7) ChIP-seq, and anti-H3K4me3 CUT&RUN in parental and  UBR7KO cells. Plots are centered on TSS that­­­­­ show changes in ATAC-seq signal in  UBR7KO versus parental cells. Sites are clustered by unsupervised k-means analysis. Cluster color key is defined by cluster labels.",
    "ncbi_link": "UBR7: 55148"
  },
  {
    "caption": "A) Representative images of TgN3R182C150, sham- and NOTCH3  EGF1-5-immunized mice  at 7 months of age  and TgN3R182C150 at 18 months of age. Representative images show brain arteries  of TgN3R182C150 (7 and 18 months), sham and NOTCH3  EGF1-5-immunized mice stained  with a monoclonal antibody against NOTCH3  ECD (1E4, red) and an α-SMA  antibody (green). Scale bar =20µm. B) Quantification of NOTCH3  ECD deposits (numbers per 1,000 μm2) and NOTCH3  ECD stained  area and average size per vessel  revealed no decrease in NOTCH3  ECD deposition in brain arteries  between NOTCH3  EGF1-5 -immunized (n=10), sham (n=8) and  non-vaccinated  (n=6) TgN3R182C150 mice  at 7 months of age. NOTCH3  ECD deposits (numbers per 1,000 μm2) and NOTCH3  ECD stained  area and average size per vessel  increases significantly in the TgN3R182C150 mice  at 18 months (n=3) of age versus NOTCH3  EGF1-5 -immunized (n=10), sham (n=8) and non-vaccinated (n=6) TgN3R182C150 mice  at 7 months of age. Statistical significance was assessed using a Brown-Forsythe and Welch ANOVA tests followed by Dunnett's T3 multiple comparisons. (NOTCH3  ECD deposits (% of vessel  area): 7 m.o. vs. Sham, ns P=0.9424; 7 m.o. vs. Vaccinated, ns P=0.9809; 7 m.o. vs. 18 m.o.**P=0.0046; Sham vs. Vaccinated, ns P=0.9999; Sham vs. 18 m.o. **P=0.0032; Vaccinated vs. 18 m.o. **P=0.0032). NOTCH3  ECD deposits (number/1000 um2): 7 m.o. vs. Sham, ns P=0.7877; 7 m.o. vs. Vaccinated, ns P=0.8358; 7 m.o. vs. 18 m.o.**P=0.0069; Sham vs. Vaccinated, ns P=0.9995; Sham vs. 18 m.o. **P=0.0044; Vaccinated  vs. 18 m.o. *P=0.0104). NOTCH3  ECD deposits size: 7 m.o. vs. Sham, ns P=0.1169; 7 m.o. vs. Vaccinated, ns P>0.9999; 7 m.o. vs. 18 m.o.***P=0.0009; Sham vs. Vaccinated, ns P=0.0577; Sham vs. 18 m.o. **P=0.007; Vaccinated  vs. 18 m.o. ****P<0.0001, ns=non-significant). Error bars indicate standard error of the mean (SEM).",
    "ncbi_link": "N3: 4854"
  },
  {
    "caption": "A) Representative images of TgN3R182C150, sham- and NOTCH3  EGF1-5-immunized mice  at 3, 7 and 18 months of age. Representative images show brain arteries  and capillaries  of TgN3R182C150, sham and NOTCH3  EGF1-5-immunized mice stained  with a monoclonal antibody against NOTCH3  ECD (1E4, red) and an anti-perlecan  antibody (green). Scale bar =20µm. B) Quantification of NOTCH3  ECD deposits (numbers per 1,000 μm2) and NOTCH3-ECD stained  area and average size per vessel   revealed a significant increase in NOTCH3  ECD deposition in brain arteries  and capillaries  between non-vaccinated  3 months old TgN3R182C150 (n=3) and 7 months old TgN3R182C150 (n=6) mice  and 18 months old TgN3R182C150 (n=3). Quantification of NOTCH3-ECD deposits (numbers per 1,000 μm2) and NOTCH3-ECD stained  area and average size per vessel  revealed a significant decrease in NOTCH3-ECD deposition in brain arteries  and capillaries  between NOTCH3  EGF1-5 -immunized (n=11), sham (n=8) and non-vaccinated  TgN3R182C150 (n=6) mice. Statistical significance was assessed using a Brown-Forsythe and Welch ANOVA tests followed by Dunnett's T3 multiple comparisons. (NOTCH3  ECD deposits (% of vessel  area): 3 m.o. vs. 18 m.o. **P=0.0029; 3 m.o. vs. 7 m.o. ***P=0.0004; 7 m.o. vs. Sham, ns P=0.7326; 7 m.o. vs. Vaccinated, **P=0.003; Sham vs. Vaccinated, ****P<0.0001). NOTCH3  ECD deposits (number/1000 um2): 3 m.o. vs. 18 m.o. **P=0.0038; 3 m.o. vs. 7 m.o. ***P=0.0002; 7 m.o. vs. Sham, ns P=0.9913; 7 m.o. vs. Vaccinated, *P=0.021; Sham vs. Vaccinated, ***P=0.001). NOTCH3  ECD deposits size: 3 m.o. vs. 18 m.o. *P=0.0215; 3 m.o. vs. 7 m.o. **P=0.0029; 7 m.o. vs. Sham, ns P=0.3622; 7 m.o. vs. Vaccinated, *P=0.0428; Sham vs. Vaccinated, **P=0.0038, ns= non-significant). Dotted lines indicate quartiles and dashed thicker lines are the median.",
    "ncbi_link": "N3: 4854"
  },
  {
    "caption": "A) NOTCH3  ECD was detected in the whole blood serum  of the non-treated TgN3R182C150 mice  at three months (n=9) of age and further increased at seven months (n=6) of age. Serum from Notch3  -/- and C57Bl6/J WT mice  were included as negative controls. Statistical analysis was performed using unpaired student t test with Welch's correction. (3 m.o. vs 7 m.o. ***P=0.0005). Error bars indicate standard error of the mean (SEM).",
    "ncbi_link": "N3: 4854
Notch3: 18131"
  },
  {
    "caption": "B) NOTCH3  ECD in the TgN3R182C150 mice  was significantly reduced in the vaccinated  (n=10) TgN3R182C150 mice  vs sham (n=9). Statistical analysis was performed using unpaired student t test with Welch's correction. (Sham vs Vaccinated  *P=0.0196). Error bars indicate standard error of the mean (SEM).",
    "ncbi_link": "N3: 4854"
  },
  {
    "caption": "A) Representative images show microglia stained  with anti-CD68  antibody (red) and Iba1  antibody (green). Scale bar=20µm. B) Quantification of CD68-stained  area revealed a significant increase in the % of microglia  and microglia  area between N3  EGF1-5-immunized (n=6), sham (n=4) and non-vaccinated TgN3R182C150 (n=5) mice. Statistical significance was assessed using an ordinary one-way ANOVA followed by Tukey's multiple comparisons test. (% microglia  with CD68 staining: 7 m.o. vs. Sham ns P=0.7393; Sham vs. Vaccinated  **P=0.0087. CD68 staining  (% of microglia  area): 7 m.o. vs. Sham ns P=0.9131; Sham vs. Vaccinated  *P=0.0157, ns=non-significant). Error bars indicate standard error of the mean (SEM).",
    "ncbi_link": "N3: 4854"
  },
  {
    "caption": "C) Representative images of TgN3R182C150, sham- and NOTCH3  EGF1-5-immunized mice  at 7 months of age stained  with a monoclonal antibody against NOTCH3  ECD (1E4, red) and an antibody against microglia  (Iba1, green). Scale bar=20µm. D) Quantification of NOTCH3  ECD deposits (numbers per 1,000 μm2) and NOTCH3  ECD stained  area and average size per microglia  revealed no alterations between the NOTCH3  EGF1-5-immunized (n=11), sham (n=8) and non-vaccinated  TgN3R182C150 (n=6) mice  at 7 months of age. Statistical significance was assessed using an ordinary one-way ANOVA followed by Tukey's multiple comparisons test. (% microglia with NOTCH3  ECD deposits: 7 m.o. vs. Sham ns P=0.7997; Sham vs. Vaccinated  ns P=0.0526. NOTCH3  ECD deposits (% of microglia  area): 7 m.o. vs. Sham ns P=0.5362; Sham vs. Vaccinated  ns P=0.8059. NOTCH3  ECD deposits (number/1000 um2): 7 m.o. vs. Sham ns P=0.8392; Sham vs. Vaccinated  ns P=0.5777. NOTCH3  ECD deposits size: 7 m.o. vs. Sham ns P=0.6664; Sham vs. Vaccinated  ns P=0.8787, ns=non-significant). Error bars indicate standard error of the mean (SEM).",
    "ncbi_link": "N3: 4854"
  },
  {
    "caption": "Immunoblots and qRT-PCRs showing that expression levels of miR-203, miR-200, and E-cadherin are increased after ZEB1 knockdown in Panc1, MDA-MB-231. Vice versa, the drug-resistant clones of BxPC3, H358, and DU-145 show increased expression of ZEB1 and decreased expression of the miRNAs and E-cadherin. n = 3, mean ± SEM, except for H358 (data from microarray). Unpaired Student's t-test.",
    "ncbi_link": "miR-200: 406985///406984///406983
miR-203: 406986
ZEB1: 6935"
  },
  {
    "caption": "Lentiviral overexpression of miR-200c and miR-203 in Panc1 and hPaca1 induces sensitivity to gemcitabine treatment as measured by MTT assay. For the changes in EC50 values, see Table1. n = 3, mean ± SEM, Dunnett's multiple comparisons test (P-values in the graphs are *P = 0.01-0.05, **P = 0.001-0.01, ***P < 0.001, and ****P < 0.0001; for exact P-values, see Supplementary Table S4).",
    "ncbi_link": "miR-200c: 406985
miR-203: 406986"
  },
  {
    "caption": "Overexpression of miR-203 decreases expression of the anti-apoptotic factor survivin and sensitizes to gemcitabine-triggered apoptosis as evaluated by cleaved caspase-3 in Western blot and immunofluorescence. Panc1 and hPaca1 were treated with 50 and 5 nM gemcitabine, respectively, for 48 h. Scale bar 20 μm.",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "MTT assay showing increase in gemcitabine resistance after inhibition of endogenous miRNAs in hPaca2 by specific antagomirs against miR-203 or all miR-200 members. For the changes in EC80 values, see Table1. n = 3, mean ± SEM, Dunnett's multiple comparisons test (P-values in the graphs are *P = 0.01-0.05, **P = 0.001-0.01, ***P < 0.001, and ****P < 0.0001; for exact P-values, see Supplementary Table S4).",
    "ncbi_link": "miR-200: 406985///406984///406983
miR-203: 406986"
  },
  {
    "caption": "Overexpression of miR-203 shows reduced numbers of the CD24/CD44 double-positive cancer stem cell population as determined by FACS analysis. The arrow indicates the reduction in the CD24 high subpopulation and reduction in CD133 by miR-203 overexpression in hPaca1 cells.",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "Cancer stem cell sphere assay showing reduced sphere-forming capacity of Panc1 and hPaca1 in miR-203 overexpression cells. Colonies with a diameter greater than 75 μM for Panc1 and greater 30 μM for hPaca1 cells were counted as spheres. n = 3, mean ± SEM, Mann-Whitney U-test.",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "B, C Histone marks were analyzed using ChIP coupled to qRT-PCR for Panc1 control versus shZEB, MDA-MB-231 control versus shZEB (B), and BxPC3 control versus gemcitabine resistant (gr) (C). In MDA-MB-231 and Panc1, the active histone marks H3K4me3, H3ac, H4ac, and H3K9ac were enriched. Vice versa, in the drug-resistant clones of BxPC3, the active marks were reduced in the CpG islands. The repressive histone mark H3K27me3 was not detectable in the miR-200 loci, but in the loci of miR-203 and E-cadherin in Panc1 and MDA-MB-231. DNA methylation status was determined by bisulfite sequencing. Depletion of ZEB1 in MDA-MB-231 resulted in almost complete demethylation, whereas the selection of drug-resistant, ZEB1-expressing clones in BxPC3 induced complete methylation. n = 2 (Panc1) or 3 (MDA-MB-231 and BxPC3), mean ± SEM; unpaired Student's t-test.",
    "ncbi_link": "E-cadherin: 999
miR-200: 406983///406985///406984
miR-203: 406986
ZEB: 6935
ZEB1: 6935"
  },
  {
    "caption": "Heat map showing the relative expression levels after drug treatment for 48 h in Panc1. Values measured by qRT-PCR were depicted with the software GENE-E. Only mocetinostat upregulated the miRNAs and downregulated ZEB1.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "Relative expression of indicated genes in Panc1 measured by qRT-PCR after treatment with different HDAC inhibitors. Note the downregulation of ZEB1 and upregulation of miR-203, miR-200, and E-cadherin by mocetinostat. n = 3, mean ± SEM; unpaired Student's t-test. For significance, see Supplementary Table S1.",
    "ncbi_link": "E-cadherin: 999
miR-200: 406983///406985///406984
miR-203: 406986
ZEB1: 6935"
  },
  {
    "caption": "Chromatin immunoprecipitation analysis validated mocetinostat-induced (1 μM, 48 h) enrichment of the active histone marks H3ac, H4ac, H3K9ac, and H3K4me3 at ZEB1 target gene loci in Panc1. n = 3, mean ± SEM; unpaired Student's t-test.",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "Mocetinostat treatment reduced expression of the anti-apoptotic miR-203 target survivin and sphere-forming capacity in Panc1 when pre-treated with mocetinostat for 48 h. n = 3, mean ± SEM; Mann-Whitney U-test.",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "MTT assays comparing the effects of docetaxel and mocetinostat in the prostate cancer cell line DU-145 and the docetaxel-resistant subclone DU-145 DR (left). Mocetinostat treatment of DU-145 DR downregulates ZEB1, upregulates E-cadherin, miR-200, and miR-203 expression. For relative miRNA expression, the expression levels in original DU-145 were set to 1 (middle panels, the immunoblot panel derives from the same experiment shown in Fig1A). Mocetinostat sensitizes DU-145 DR to docetaxel (right). For calculation of the CI and synergy between the drugs, see Table2. n = 3, mean ± SEM, Dunnett's multiple comparisons test (P-values in the graphs are *P = 0.01-0.05; for exact P-values, see Supplementary Table S4).",
    "ncbi_link": "miR-200: 406983///406985///406984
miR-203: 406986"
  },
  {
    "caption": "Representative pictures of in situ hybridization for miR-203 and control probe showing gain of miR-203 and associated loss of ZEB1 detected by immunohistochemistry in serial sections of mocetinostat-treated xenograft tumors. Scale bar 40 μm, inserts for higher magnifications 5 μm. Squares indicate magnified regions.",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "Schematic outline and results for xenografts of ex vivo treated Panc1 in Foxn1 nude mice. Panc1 cells were pre-treated with mocetinostat (1 μM) and/or gemcitabine (50 nM) for 48 h, followed by a 7-day recovery period before being injected subcutaneously (left). Equal numbers of viable cells were injected in 75 μl volume. At day 9 after injection, tumor growth was detectable in all groups (lower right). To better visualize and compare tumor growth, the tumor volume at day 9 was set to 1 and the increasing slope of the tumor volume to day 37 is depicted (upper right). The individual absolute tumor volumes on day 37 (lower left) and the group medians of the absolute tumor volumes over time (lower right) are shown. For cells pre-treated with the combination of mocetinostat and gemcitabine, tumor growth was arrested. n = 4 for each treatment group; nonparametric Mann-Whitney U-test.",
    "ncbi_link": "Foxn1: 15218"
  },
  {
    "caption": "A, B Relative expression levels of miR-203 and miR-200c in pancreatic adenocarcinomas. (A) In normal versus tumor tissue of the same case (n = 6 cases), (B) in the non-recurrence (n = 10 cases) versus the recurrence group (n = 11 cases). The mean value of the lower group in each figure was set to 1. Nonparametric Mann-Whitney U-test.",
    "ncbi_link": "miR-200c: 406985
miR-203: 406986"
  },
  {
    "caption": "B Box plots of the Em/Ad expression ratios of GATA6 (left) and NKX2-1 (right) in FFPE lung tissue sections from controls (Ctrl, n=61) or lung cancer (LC, n=51) patients. Isoform-specific expression of the indicated genes was analyzed by qRT-PCR after total RNA isolation from tissue samples. Each point represents one sample.",
    "ncbi_link": "GATA6: 2627
NKX2-1: 7080"
  },
  {
    "caption": "C Box plots of Em/Ad of GATA6 (top) or NKX2-1 (bottom) show that high Em/Ad ratios in LC samples are maintained among ethnic groups (left) and gender (right). GER, samples collected in Germany; MEX, samples collected in Mexico.",
    "ncbi_link": "GATA6: 2627
NKX2-1: 7080"
  },
  {
    "caption": "D Box plots of Em/Ad of GATA6 (left) or NKX2-1 (right) in FFPE lung tissue sections from controls or LC patients. Samples were staged according to the TNM Classification (UICC, 7th edition).",
    "ncbi_link": "GATA6: 2627
NKX2-1: 7080"
  },
  {
    "caption": "A Box plots of the Em/Ad expression ratios of GATA6 (left) and NKX2-1 (right) in EBCs from controls (Ctrl, n=65) or lung cancer (LC, n=48) patients (training set). Each point represents one sample.",
    "ncbi_link": "GATA6: 2627
NKX2-1: 7080"
  },
  {
    "caption": "Cells were grown in MHB-ca medium without or with 20 mM glucose as indicated. (B) PndhC and PndhF YFP reporter constructs were used for following gene expression and data was normalized by growth. Data are expressed as average ± SEM of three independent experiments. *** Denotes p < 0.001 compared to ndhC expression in WT strain grown in MHB-ca medium via two-way ANOVA with Tukey's posttest.",
    "ncbi_link": "YFP: 
ndhF: 3919222
ndhC: 3919225"
  },
  {
    "caption": "(A) PndhC and PndhF YFP reporter constructs were used to follow gene expression under the biofilm growth conditions. Data collected after 24 h of static incubation was normalized by optical density at 600 nm. Data are expressed as average ± SEM of three independent experiments. No significant differences were found when ndhC expression in WT strain was compared via one-way ANOVA with Dunnett's posttest.",
    "ncbi_link": "YFP: 
ndhF: 3919222
ndhC: 3919225"
  },
  {
    "caption": "(E) Hemolytic activity of Newman ∆ndhC strain overexpressing the N. gonorrhea acyl-ACP synthetase and grown aerobically for 20 h in MHB-ca medium. Data are expressed as average ± SD of four independent experiments. ** Denotes p < 0.005 compared to ∆ndhC strain with the empty plasmid via Student's t-test.",
    "ncbi_link": "acyl-ACP synthetase: 
ndhC: 3919225"
  },
  {
    "caption": "(F) Biofilm formation of Newman ∆ndhC strain overexpressing the N. gonorrhea acyl-ACP synthetase and grown under biofilm producing conditions. Data are expressed as average ± SD of three independent experiments performed by octuplicates. *** Denotes p < 0.001 compared to ∆ndhC strain with the empty plasmid via Student's t-test.",
    "ncbi_link": "acyl-ACP synthetase: 
ndhC: 3919225"
  },
  {
    "caption": "C The peritoneal recruitment of classical monocytes after IP injection of PBS (n = 6) or TG in C57BL/6J WT (dark green, n = 10 mice) and Gal-3-/- (black, n = 5 mice) mice was assessed after 18 h. Where indicated, the mice received an IP injection of CXCR4 antagonist AMD 3465 12 hours prior to the experiment.",
    "ncbi_link": "Gal-3: 16854"
  },
  {
    "caption": "Filter Trap with 5-fold serial dilution and quantification of crude protein extract from SERF2 CRISPR  deletion mutant cells transiently transfected with HA-polyQ74 and either wild-type SERF2, empty vector or SERF2  charge mutant (I), Western blots for HA-Q74, SERF2  and Tubulin  expression were included as controls For all Filter Trap assays, the depicted blots  are from one representative experiment of four biological replicates. The average of four biological replicates with each three or four technical replicates is represented in the graphs. Data are represented as mean ± SD, significance was calculated using a one-way ANOVA, followed by a post-hoc Bonferroni multiple comparisons test. (I) p<0.0001, **p < 0.01; ***p < 0.001.",
    "ncbi_link": "CRISPR: 
SERF2: 10169"
  },
  {
    "caption": "Filter Trap  with 5-fold serial dilution and quantification of crude protein extract from SERF2 CRISPR  deletion mutant cells transiently transfected with HA-polyQ74 and either wild-type SERF2, empty vector or SERF2  control mutant (J) or SERF2  charge mutant. Western blots for HA-Q74, muHA-Q74, SERF2  and Tubulin  expression were included as controls For all  Filter Trap assays, the depicted blots  are from one representative experiment of four biological replicates. The average of four biological replicates with each three or four technical replicates is represented in the graphs. Data are represented as mean ± SD, significance was calculated using a one-way ANOVA, followed by a post-hoc Bonferroni multiple comparisons test. (J)=0.0003, (K) p=0.9130 **p < 0.01; ***p < 0.001.",
    "ncbi_link": "CRISPR: 
SERF2: 10169"
  },
  {
    "caption": "(B) Representative images of Q40 and Q40;moag-4 charge mutant animals. Scale bar, 75 mm. (C) Representative quantification of the number of aggregates in Q40 worms with moag-4 deletion or expression of either wild-type moag-4, moag-4 charge mutant or moag-4 ctrl mutant. The results shown are representative experiments of three biological replicates of n=20 worms in L4 stage. Data are represented as mean ± SD and significance was calculated using a one-way ANOVA, followed by a post-hoc Bonferroni multiple comparisons test. ****p < 0.0001.",
    "ncbi_link": "moag-4: 171764"
  },
  {
    "caption": "(E) Number of aggregates per  retro vesicular ganglion  from three independent cohorts of the indicated  Aβ1-42 strains with moag-4  deletion mutant (del (tm4909)) n=11, moag-4  control mutant (ctrl mutant) n=12, moag-4  charge mutant (charge mutant) n=17, and wild-type n=15. Data are represented as mean ± SD. One-way ANOVA + Bonferroni post-hoc test for significance (* p < 0.05, **** p < 0.0001).",
    "ncbi_link": "moag-4: 171764"
  },
  {
    "caption": "(A) lid-1(xd288) and atgl-1(xd314) mutants show LD accumulation in most neurons in C. elegans, including neurons in the head region, tail and ventral nerve cord. xdIs109 is a stable transgenic line with pan-neuronal expression of the LD marker PLIN1::GFP. The white arrows indicate PLIN1::GFP-positive LDs in the ventral nerve cord of mutants. Scale bar: 20 μm. The right panels depict the head region. Scale bar: 5 μm. The insets in the right panels are enlarged views of PLIN1::GFP rings, representing LDs.",
    "ncbi_link": "atgl-1: 175910
lid-1: 172888"
  },
  {
    "caption": "(E) Oil red O staining show dramatically increased neutral lipids in the head region of lid-1(xd288) and atgl-1(xd314) compared with N2. Scale bar: 10 μm.",
    "ncbi_link": "atgl-1: 175910
lid-1: 172888"
  },
  {
    "caption": "(F-H) EM images of neurons. The red dashed line marks the outline of neurons. The red arrows mark LDs. Scale bar: 0.5 μm. The scale bar in enlarged images is 100 nm. (I) Serial sections of atgl-1(xd314) show two LDs (indicated by blue and red arrows) in a neuron cell body. Scale bar: 0.5 μm. ",
    "ncbi_link": "atgl-1: 175910"
  },
  {
    "caption": "(A) The expression pattern of atgl-1 viewed by Patgl-1::GFP transcriptional fusion reporter. Patgl-1::GFP expression is high in intestine. Relatively low fluorescent signals are found in nerve ring, motor neuron commissure, ventral nerve cord and tail. Scale bar: 20 μm.",
    "ncbi_link": "GFP: 
atgl-1: 175910"
  },
  {
    "caption": "(D) Visualizing LDs in head neurons with the xdIs109 reporter in different genetic backgrounds. The accumulation of LDs in head neurons of atgl-1(xd314) mutants can be rescued by expressing wild-type atgl-1 in neurons (Punc-119::atgl-1), but not in intestine (Pvha-6::atgl-1), glia (Phlh-17::atgl-1) or hypodermis (Pajm-1::atgl-1). Scale bar: 5 μm. (E) Quantification of the number of LDs in head neurons in different genetic backgrounds. Each dot represents one worm. The data were analyzed using one-way ANOVA with Dunnett's multiple comparison test. Asterisks denote significant differences as compared to the control xdIs109. ns: not statistically significant. ****P < 0.0001. Data show mean ± SEM. n ≥ 7. ",
    "ncbi_link": "ajm-1: 181148
atgl-1: 175910
hlh-17: 185460
unc-119: 176519
vha-6: 174743"
  },
  {
    "caption": "(F) Neuron-specific knockout of atgl-1 causes LD accumulation in neurons, similar to atgl-1(xd314) mutants. Scale bar: 5 μm. (G) Quantification of the number of LDs in head neurons in different genetic backgrounds. Each dot represents one worm. The data were analyzed using one-way ANOVA with Dunnett's multiple comparison test. Asterisks denote significant differences as compared to the control xdIs109. t-test was used between the groups under the crossbars. ns: not statistically significant. ****P < 0.0001. Data show mean ± SEM. n ≥ 9 ",
    "ncbi_link": "atgl-1: 175910"
  },
  {
    "caption": "(A) LDs accumulate in touch neurons in atgl-1(xd314) visualized by SRS (Stimulated Raman Scattering). The zdIs5 reporter marks touch neurons. The white arrows indicate LDs in touch neurons in atgl-1(xd314). Scale bar: 10 μm.",
    "ncbi_link": "atgl-1: 175910"
  },
  {
    "caption": "(B) atgl-1(xd314) and lid-1(xd288) show a gentle touch sensation defect, which is rescued by the neuron-specific expression of atgl-1 and lid-1, respectively. The fat-4 mutation enhances the touch sensation defect in atgl-1(xd314) and lid-1(xd288). Wild type and mec-4(u253) act as the negative control and positive control, respectively. The data were analyzed using Kruskal-Wallis test with Dunn's test. Asterisks denote significant differences as compared to wild type. ns: not statistically significant. **P < 0.01, ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. # signify significant differences between the groups under the crossbars. ##P < 0.01. Data show mean ± SEM. Number of worms analyzed for each strain n =25.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
lid-1: 172888
mec-4: 181728"
  },
  {
    "caption": "(C) The percentage of worms that have three or more surviving touch neurons in different genetic backgrounds in (B). The lid-1(xd288) and atgl-1(xd314) mutations significantly increase the number of surviving neurons. Neuron-specific expression of atgl-1 or lid-1 reverses the protective effect of atgl-1 or lid-1 mutation. The data were analyzed using one-way ANOVA with Turkey's multiple comparison test. Asterisks signify significant differences between the groups under the crossbars. ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n = 5, with at least 50 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
lid-1: 172888"
  },
  {
    "caption": "(D) The percentage of worms that have three or more surviving touch neurons in different genetic backgrounds. Mutations of fat-1, fat-3 and fat-4 significantly enhance the suppression effect of atgl-1(xd314) in preventing the neurodegeneration of mec-4(d). The data were analyzed using one-way ANOVA with Bonferroni's multiple comparison test. ### and #### denote significant differences as compared to atgl-1(xd314); mec-4(d). Asterisks signify significant differences as compared to mec-4(d). ns: not statistically significant. ****P < 0.0001. ###P < 0.001, ###P < 0.0001. Data show mean ± SEM. Number of experiments n ≥ 3, with at least 50 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-1: 178291
fat-3: 177820
fat-4: 177819
mec-4: 181728"
  },
  {
    "caption": "(E) The percentage of worms that have three or more surviving touch neurons in different genetic backgrounds supplemented with different fatty acids. AA and EPA but not LA significantly enhance the neurodegeneration triggered by mec-4(d). The data were analyzed using one-way ANOVA with Bonferroni's multiple comparison test. Asterisks signify significant differences between the groups under the crossbars. ns: not statistically significant. ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n ≥ 3, with at least 50 animals per strain analyzed in each experiment.",
    "ncbi_link": "mec-4: 181728"
  },
  {
    "caption": "(A) Lipidomic data show that the relative content of total C20:3 is increased in atgl-1(xd314); mec-4(d), fat-4(wa14); mec-4(d) and atgl-1(xd314); fat-4(wa14); mec-4(d). The increase is greatest in mutants with the fat-4 mutation. (B) Lipidomic data show that the relative content of total C20:4 is increased in atgl-1(xd314); mec-4(d), fat-4(wa14); mec-4(d) and atgl-1(xd314); fat-4(wa14); mec-4(d). The increase is greatest in mutants with the fat-4 mutation. (C) Lipidomic data show that the relative content of total C20:5 is slightly increased in atgl-1(xd314); mec-4(d) but is dramatically decreased in fat-4(wa14); mec-4(d) and atgl-1(xd314); fat-4(wa14); mec-4(d), which matches the role of FAT-4 in synthesizing C20:5 (EPA). Data information The data were analyzed using two-way ANOVA with Dunnett's multiple comparison test. Asterisks denote significant differences as compared to mec-4(d). ns: not statistically significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n=5, with about 10,000 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
FAT-4: 177819
mec-4: 181728"
  },
  {
    "caption": "(D) The percentage of C20:3-, C20:4- or C20:5-containing TAGs to total lipids containing the same PUFA in different genetic backgrounds. The percentage of C20:4-containing TAGs to total lipids containing C20:4 is significantly increased in atgl-1 and fat-4 single mutants. The percentage is further increased in atgl-1 and fat-4 double mutant. Data information: FA: free fatty acids; TAG: triacylglycerol; PL: phospholipids. The data were analyzed using two-way ANOVA with Dunnett's multiple comparison test. Asterisks denote significant differences as compared to mec-4(d). ns: not statistically significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n=5, with about 10,000 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
mec-4: 181728"
  },
  {
    "caption": "(E) The percentage of C20:3-, C20:4- or C20:5-containing phospholipids to total lipids containing the same PUFA in different genetic backgrounds. The percentage of C20:4-containing phospholipids to total lipids containing C20:4 is significantly decreased in atgl-1 and fat-4 single mutants. The percentage is further decreased in atgl-1 and fat-4 double mutant. Data information: FA: free fatty acids; TAG: triacylglycerol; PL: phospholipids. The data were analyzed using two-way ANOVA with Dunnett's multiple comparison test. Asterisks denote significant differences as compared to mec-4(d). ns: not statistically significant. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n=5, with about 10,000 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
mec-4: 181728"
  },
  {
    "caption": "(F) The percentage of worms that have three or more surviving touch neurons in different genetic backgrounds. mboa-7 mutation significantly increases the percentage of three or more surviving touch neurons in mec-4(d), atgl-1(xd314); mec-4(d), fat-4(wa14); mec-4(d) and atgl-1(xd314); fat-4(wa14); mec-4(d). The data were analyzed using one-way ANOVA with Bonferroni's multiple comparison test. Asterisks signify significant differences between the groups under the crossbars. **P < 0.01, ****P < 0.0001. Data show mean ± SEM. Number of experiments n ≥ 4, with at least 50 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
mboa-7: 181252
mec-4: 181728"
  },
  {
    "caption": "(G) The percentage of C20:4-containing phospholipids to total lipids that have C20:4 is dramatically decreased in mboa-7(gk399); atgl-1(xd314); fat-4(wa14); mec-4(d). The data were analyzed using one-way ANOVA with Dunnett's multiple comparison test. Asterisks signify significant differences as compared to mec-4(d). ***P < 0.001, ****P < 0.0001. Data show mean ± SEM. Number of experiments n=5, with about 10,000 animals per strain analyzed in each experiment.",
    "ncbi_link": "atgl-1: 175910
fat-4: 177819
mboa-7: 181252
mec-4: 181728"
  },
  {
    "caption": "A) Manhattan plot of genome-wide association for the levels of hepatic Pex16 transcript, where the only significant locus appears directly surrounding the genomic location (red arrow). Significant cut-offs are shown for FDR (blue) and Bonferroni (red). The peak SNP (rs27364570) is highlighted with a dark red box. Y-axis shows the -log10(pvalue) vs x-axis showing each SNP measured. P-values for GWAS associations were calculated using FaST-LMM.",
    "ncbi_link": "Pex16: 18633"
  },
  {
    "caption": "B) Allelic distribution comparing GG vs TT (x-axis) for the peak SNP of the Pex16 association (rs27364570), where the abundance of each LPC species (y-axis) showed significantly different levels depending on the allele. P-values for GWAS associations were calculated using FaST-LMM. Boxplots show mean (middle line), 25-75% quantiles (colored box) and 5-95% quantiles (vertical lines)",
    "ncbi_link": "Pex16: 18633"
  },
  {
    "caption": "C) Correlations between expression of hepatic Pex16 with LPC species and phenotypic traits. Box color indicates bicor value, where all relationships are positive and number in each box shows p-value for each correlation. Pvalues were calculated based on significance of regression (students test) and adjusted for multiple comparisons (FDR = 0.05)",
    "ncbi_link": "Pex16: 18633"
  },
  {
    "caption": "B) Locuszoom plots showing the focused genomic region (x-axis) plotted against the -log10 (p-value) of association for liver mRNA expression of Map2k6. P-values for GWAS associations were calculated using FaST-LMM",
    "ncbi_link": "Map2k6: 26399"
  },
  {
    "caption": "(C) Correlations between hepatic expression of Map2k6 and all TAGs identified in the study. Blue represents negative correlations.",
    "ncbi_link": "Map2k6: 26399"
  },
  {
    "caption": "F) Comparison of total hepatic TAG between Map2k6-overexpressing mice (black bar) and control mice (empty bar).",
    "ncbi_link": "Map2k6: 26399"
  },
  {
    "caption": "G) Differences in total phospholipid (PC), total cholesterol (TC) and unesterified cholesterol (UC) between Map2k6-overexpressing mice (black bars) and control mice (empty bars).",
    "ncbi_link": "Map2k6: 26399"
  },
  {
    "caption": "A) Manhattan plot of genome-wide association for expression of Ifi203 in liver. Red line shows Bonferroni-corrected threshold and blue shows an FDR =0.01 pvalue of significance calculated based on FaST-LMM pvalues.",
    "ncbi_link": "Ifi203: 15950"
  },
  {
    "caption": "B-D) Allelic variation plots showing the peak SNP for Ifi203 expression (rs31614030) at the CC or TT allele (x-axis) plotted against expression of Ifi203 (B), levels of hepatic PC(38:3) (C), and plasma insulin levels (D). Red line shows Bonferroni-corrected threshold and blue shows an FDR =0.01 pvalue of significance calculated based on FaST-LMM pvalues.",
    "ncbi_link": "Ifi203: 15950"
  },
  {
    "caption": "E-G) Correlation between the parameters listed above showing significant relationships between hepatic Ifi203 and PC(38:3) (E), hepatic Ifi203 and plasma insulin levels (F) or PC (38:3) and plasma insulin (G). Pvalues were calculated based on significance of regression (students test) and adjusted for multiple comparisons (FDR = 0.05)",
    "ncbi_link": "Ifi203: 15950"
  },
  {
    "caption": "Mice receiving the control virus (open bars) or shIfi203 (black bars) were analyzed for liver expression of Ifi203 (I), total PC levels in liver (J) P-values calculated using a students t-test between groups. Data represent means ± SEM (n =4-5 per group).",
    "ncbi_link": "Ifi203: 15950"
  },
  {
    "caption": "Mice receiving the control virus (open bars) or shIfi203 (black bars) were analyzed for liver expression of Pemt (K), total liver TAG content (L), or plasma insulin levels (M). P-values calculated using a students t-test between groups. Data represent means ± SEM (n =4-5 per group).",
    "ncbi_link": "Ifi203: 15950
Pemt: 18618"
  },
  {
    "caption": "(A) ROS burst response in wild-type (WT) and map4k4 lines in response to 1 μM flg22. Values are means ± SEM, n = 16 (biological replicates). Results are representative of three independent experiments. Statistical analysis was performed using a one-way ANOVA with Tukey post-test, p < 0.01. Data information Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different.",
    "ncbi_link": "map4k4: 831324"
  },
  {
    "caption": "(B) qRT-PCR analysis of the expression of PTI marker gene FRK1 in wild-type and map4k4-1 seedlings 1 h after treatment with 1 μM flg22. Bars represent means ± SD based on three biological replicates, p < 0.01. Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different.",
    "ncbi_link": "map4k4: 831324
FRK1: 816436"
  },
  {
    "caption": "(D) Heat map of gene expression response to flg22 in wild-type and map4k4-1, red and blue indicate high and low expression levels.",
    "ncbi_link": "map4k4: 831324"
  },
  {
    "caption": "(A) left panel, map4k4-1 shows enhanced resistance to Pseudomonas syringae pv. tomato DC3000. The growth of Pst DC3000 after inoculation in the indicated genotypes (Col-0, white bars, map4k4-1, green bars). Bacterial titers were determined 2 hours (day 0) and 3 days after inoculation. Right panel, disease symptoms of wild-type and map4k4-1 at 3 days after inoculation. Values are the means ± SD, n = 6 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.",
    "ncbi_link": "map4k4: 831324"
  },
  {
    "caption": "(B) map4k4-1 disease resistance phenotype was recovered to wild-type levels in two independent complementation lines, c867 and c872. Bacterial titers were determined as described above. Values are the means ± SD, n = 6 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.",
    "ncbi_link": "map4k4: 831324"
  },
  {
    "caption": "(C) qRT-PCR analysis of PR1 expression levels in Col-0, map4k4-1 and c867 after mock (MgCl2) or Pst DC3000 inoculation, values are the means ± SD, n = 3 (biological replicates), p < 0.01. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.",
    "ncbi_link": "map4k4: 831324
PR1: 815949"
  },
  {
    "caption": "(D) Flg22-protection assay. Col-0, map4k4-1 and c867 were pretreated with H2O or flg22 1 day before Pst DC3000 inoculation. The bacterial population was measured 3 days after infection. Values are the means ± SD, n = 6. **p < 0.01, Results are representative of three independent experiments. Data information: Statistical analysis were performed using a one-way ANOVA with Newman-Keuls multiple comparison tests or t-tests. n.s. indicate non-significant.",
    "ncbi_link": "map4k4: 831324"
  },
  {
    "caption": "(C) BiFC visualization of interaction between MAP4K4 and BIK1 in Arabidopsis mesophyll protoplasts. BIK1-nYFP and MAP4K4-cYFP were co-expressed in protoplasts to show fluorescence of complemented YFP signal (green), 14 h after transformation, the results were photographed by confocal laser scanning microscopy, scale bars = 10 µm. Chl indicates Chloroplast, BF indicate Bright field. nYFP and cYFP constructs were used as empty controls. MAP3K5-K375M and MKK4 were used as control.",
    "ncbi_link": "cYFP: 
MAP3K5: 
MAP4K4: 
nYFP: 
BIK1: 818549
MKK4: 841591"
  },
  {
    "caption": "(D) MAP4K4 associates with BIK1 in vivo by Co-IP. BIK1-HA and MAP4K4-GFP were co-expressed in plants by crossing of 35S::BIK1-HA and 35S::MAP4K4-GFP transgenic lines. 14 days old plants were treated (+) with 1 µM flg22 or H2O (-) for 10 min. GFP trap beads were used for immunoprecipitation, and target proteins were detected by western blots using anti-GFP or anti-HA antibodies. The predicted molecular weight of BIK1-HA, MAP4K4-GFP is 49.3 kDa and 103.8 kDa respectively.",
    "ncbi_link": "GFP: 
HA: 
MAP4K4: 831324
BIK1: 818549"
  },
  {
    "caption": "(A) Decreased BIK1 abundance in map4k4-1. 35S::BIK1-HA was introduced into map4k4-1 by crossing, sibling lines carrying either map4k4-1 or MAP4K4 genotype were isolated from F3 generation. BIK1 levels were detected by western blot analysis using anti-HA antibodies.",
    "ncbi_link": "HA: 
map4k4: 831324
MAP4K4: 831324
BIK1: 818549"
  },
  {
    "caption": "(B) MAP4K4 regulates BIK1 accumulation through the proteasome pathway. 10 days old 35S::BIK1-HA seedlings of WT or map4k4-1 were treated with DMSO (-) or the proteasome inhibitor MG132 (50 µM) for 5h, then the plants were collected for immunoblot analysis.",
    "ncbi_link": "HA: 
MAP4K4: 831324
map4k4: 831324
BIK1: 818549"
  },
  {
    "caption": "(C) Flg22-induced BIK1 phosphorylation assay. 10 days old 35S::BIK1-HA seedlings of WT or map4k4-1 were treated with H2O (-) or 1 µM flg22 for 15 min, BIK1 phosphorylation levels were detected by mobility-shift assay using anti-HA immunoblot.",
    "ncbi_link": "HA: 
map4k4: 831324
BIK1: 818549"
  },
  {
    "caption": "(D, E and F) Identification of phosphorylation sites by LC-MS/MS analysis. Five residues in GST-BIK1-K105E were phosphorylated in vitro by HisMBP-MAP4K4. The peptide sequences are shown above the spectrum with the PH designating phosphorylated residue. In the spectrum, the matched fragment ions shows in red line for terminal series ions and in orange for immonium ions and modified ions. (G) S233 and T242 were required for BIK1 hyper-phosphorylation. BIK1-HA, BIK1S233-HA and BIK1S242-HA mutants were expressed in Col-0 protoplasts and treated with 100 nM flg22 for 15 min, BIK1 phosphorylation levels were detected by mobility-shift assay using anti-HA immunoblot. Each experiment was performed at least three times with similar results. ",
    "ncbi_link": "GST: 
HA: 
MAP4K4: 
MBP: 
BIK1: 818549"
  },
  {
    "caption": "(A) MAP4K4 associates with PP2C38 in vivo by Co-IP. MAP4K4-GFP and PP2C38-HA were co-expressed in protoplasts. GFP trap beads were used for immunoprecipitation, and target proteins were detected by western blots using anti-GFP or anti-HA antibodies. The predicted molecular weight of MAP4K4-GFP and PP2C38-HA is 103.8kDa and 48.1 kDa respectively.",
    "ncbi_link": "GFP: 
HA: 
PP2C38: 820442
MAP4K4: 831324"
  },
  {
    "caption": "(B) Identification of phosphorylation sites by LC-MS/MS analysis. In vitro phosphorylation site of HisMBP-PP2C38 by HisMBP-MAP4K4. The peptide sequence is shown above the spectrum with the PH designating phosphorylated residue. In the spectrum, the matched fragment ions shows in red line for terminal series ions and in orange for immonium ions and modified ions.",
    "ncbi_link": "MAP4K4: 
MBP: "
  },
  {
    "caption": "(C) S77 is required for flg22-induced PP2C38 band shift. PP2C38-HA and PP2C38-S77A-HA were expressed in Col-0 and map4k4 protoplasts and treated with 1µM flg22 for 30 min. The phosphorylated PP2C38 was detected by western blot mobility shift assay.",
    "ncbi_link": "HA: 
PP2C38: 820442
map4k4: 831324"
  },
  {
    "caption": "(D) flg22-induced PP2C38 band shift was compromised in map4k4 mutants. PP2C38-HA were expressed in Col-0 and map4k4 protoplasts and treated with 1µM flg22 for 30 min.",
    "ncbi_link": "HA: 
PP2C38: 820442
map4k4: 831324"
  },
  {
    "caption": "(A) BIK1 transgene restores flg22-induced ROS burst in map4k4-1. 35S::BIK1-HA WT or 35S::BIK1-HA map4k4-1 were generated by crossing as described before. ROS burst response in the indicated genotypes in response to 1 μM flg22. Values are means ± SEM, n = 16. Results are representative of three independent experiments. Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different, p < 0.05.",
    "ncbi_link": "HA: 
map4k4: 831324
BIK1: 818549"
  },
  {
    "caption": "(B) Morphological phenotype of 6-week-old of Col-0, map4k4-1, bik1 and map4k4-1 bik1 mutants.",
    "ncbi_link": "map4k4: 831324
bik1: 818549"
  },
  {
    "caption": "(C) ROS burst response in Col-0, map4k4-1, bik1 and map4k4-1 bik1 mutants. Values are means ± SEM, n = 16. Results are representative of three independent experiments. Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different, p < 0.05.",
    "ncbi_link": "map4k4: 831324
bik1: 818549"
  },
  {
    "caption": "(D) Relative expression level of PR1 in Col-0, map4k4-1, bik1 and map4k4-1 bik1mutants by qRT-PCR analysis. Values are means ± SD, n = 3 (biological replicates). Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different, p < 0.05.",
    "ncbi_link": "map4k4: 831324
bik1: 818549
PR1: 815949"
  },
  {
    "caption": "(E) Morphological phenotype of 6-week-old of Col-0, map4k4-1, map4k3 and map4k4-1 map4k3 mutants.",
    "ncbi_link": "map4k4: 831324
map4k3: 843253"
  },
  {
    "caption": "(F) Relative expression level of PR1 in Col-0, map4k4-1, map4k3 and map4k4-1 map4k3 mutants by qRT-PCR analysis. Values are means ± SD, n = 3 (biological replicates). Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different, p < 0.05.",
    "ncbi_link": "map4k4: 831324
PR1: 815949
map4k3: 843253"
  },
  {
    "caption": "(G) ROS burst response in Col-0, map4k4-1, map4k3 and map4k4-1 map4k3 mutants. Values are means ± SEM, n = 16 (biological replicates). Data information: Different letters indicate statistical significant base on one-way ANOVA with Tukey post-test, samples sharing letters are not significantly different, p < 0.05.",
    "ncbi_link": "map4k4: 831324
map4k3: 843253"
  },
  {
    "caption": "C Graph showing gene expression differences (log10-fold changes) of defined genes (X-axis) in Tsc2-deficient relative to wild-type MEFs grown in DMEM 10% FBS. The asterisks indicate significant differences with two-sided t-test (**P < 0.01, ***P < 0.001, and ****P < 0.0001; Aldh1a3 P = 0.006, Aldh2 P = 2x10-5, Aldh3a1 P = 0.004; Aldh3b1 P = 0.006; Aldh3b2, P = 0.17, Maoa P = 7x10-5, and Maob P = 7x10-4; replicates/condition n = 3, assays n = 4). The bars indicate mean ± SD. Dotted horizontal lines indicate 2-fold (top) and 0.5-fold (bottom).",
    "ncbi_link": "Aldh1a3: 56847
Aldh2: 11669
Aldh3a1: 11670
Aldh3b1: 67689
Aldh3b2: 621603
Maoa: 17161
Maob: 109731
Tsc2: 22084"
  },
  {
    "caption": "D Western blot  results (independent experiments n = 4) from Tsc2-deficient and wild-type  MEFs exposed to DMSO or treated with 20 nM everolimus for 16 hours in DMEM 10%  FBS. Loading controls are shown. The inferred  protein expression level is indicated by the ratio between the corresponding signal and loading control, standardized to the basal setting",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "A No differences of Vdac1/VDAC1 expression between MEF cell lines (replicates/condition n = 3 and independent experiments n = 2). The graph shows fold change expression (mean ± SEM) in Tsc2-deficient relative to wild-type  MEFs.",
    "ncbi_link": "Tsc2: 22084
Vdac1: 22333"
  },
  {
    "caption": "B  Flow cytometry  results (independent experiments n = 3) showing a higher percentage of MitoSOX red-positive cells in Tsc2-deficient MEFs. C Flow cytometry results (independent experiments n = 3) showing higher intensity (X-axis, single channel intensity FL3 670 nm) of MitoTracker red-positive cells in  Tsc2-deficient MEFs. ",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "D Higher  basal cell respiration (as measured by oxygen consumption, Y-axis) in Tsc2-deficient MEFs. The asterisks indicate significant difference with two-sided t-test (P = 5x10-4; replicates/condition n = 5, and independent experiments n = 3).",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "F Left panel, western blot results showing overexpression of catalase (CAT) in Tsc2-deficient MEFs, and unaffected by exposure to everolimus (independent experiments n = 2). The CAT expression level is indicated by the ratio of the corresponding signal relative to loading control and basal setting (noted as 1(ref)). Right panel, Cat overexpression (log10-fold change) in  Tsc2-deficient MEFs. The asterisks indicate significant difference with two-sided t-test (P = 1x10-2; replicates/condition n = 3, and independent experiments n = 2). The bars indicate mean ± SD. Dotted horizontal lines indicate 2-fold (top) and 0.5-fold (bottom).",
    "ncbi_link": "Cat: 12359
Tsc2: 22084"
  },
  {
    "caption": "A Overabundance of histamine in Tsc2 wild-type relative to Tsc2-deficient MEFs, both growth in DMEM 10% FBS. The asterisks indicate significant difference with two-sided t-test (P = 0.017); replicates/condition n = 5, and independent experiments n = 2). Average values are indicated with lilac-colored lines.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "D  Western blot results of HRH1, SLC22A3, and loading control from Tsc2-deficient and wild-type MEFs exposed to DMSO or treated with 20 nM everolimus for 16 hours in DMEM 10% or 0.5% FBS  (independent experiments n = 2). The expression levels are indicated by the ratio of the corresponding signal relative to loading control and basal setting",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "F Evaluation of cell viability inhibition by  loratadine alone (concentrations shown on X-axis, from 0 to 100 μM) or combined with everolimus (fixed to 20 nM) in Tsc2-deficient and wild-type MEF cultures grown in DMEM 10% FBS for 72 hours. The synergistic combination index (CIx < 1) is shown (replicates/condition n = 3, independent experiments n = 3). Each data point represents the mean and SD.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "H Percentages of viability of Tsc2-dificient and wild-type MEFs exposed to DMEM 10% or 0.5%  FBS with or without L-histidine for 72 hours. The asterisks indicate significant differences with one-sided t-test (10%  FBS, P = 0.017; 0.5%  FBS, P = 5x10-4; replicates/condition n = 4-6, independent experiments n = 2). The bars indicate mean ± SD.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "B Inhibition of Tsc2-deficient 105K tumor growth with different monotherapies, as indicated in the inset. Asterisks indicate significant reductions relative to vehicle (two-way ANOVA; clorgyline P = 0.015, loratadine P = 0.018, and rasagiline P = 0.049). Each data point represents the mean and SEM.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "C Further reduction of Tsc2-deficient 105K tumor growth by  rapamycin  combined with clorgyline or loratadine, relative to rapamycin alone. Asterisks indicate significant reductions relative to  rapamycin alone (two-way ANOVA; clorgyline P = 0.035, loratadine P = 0.045). Each data point represents the mean and SEM.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "E Inhibition of Tsc2-deficient 105K tumor growth with Maoa expression depletion using shRNAs. Asterisks indicate significant reductions relative to control pLKO (two-way ANOVA; P = 1x10-3). Each data point represents the mean and SEM.",
    "ncbi_link": "Maoa: 17161
Tsc2: 22084"
  },
  {
    "caption": "F Inhibition of Tsc2-deficient 105K tumor growth with Hrh1 expression depletion. Asterisk indicates significant reduction relative to control pLKO (two-way ANOVA; P = 0.035) . Each data point represents the mean and SEM. G Inhibition of Tsc2-deficient 105K tumor growth with administration of α-methyl-DL-histidine. Asterisk indicates significant reduction relative to vehicle (two-way ANOVA; P = 0.028). Each data point represents the mean and SEM. ",
    "ncbi_link": "Hrh1: 15465
Tsc2: 22084"
  },
  {
    "caption": "E Representative images of  hematoxylin-eosin-stained Tsc2-deficient 105K tumors treated with vehicle or monotherapies. Tumors treated with rapamycin tend to have a fascicular growth pattern with bundles of spindle cells and foci of fibrosis, whereas most of the tumors of the other treatment groups showed extensive epithelioid morphology. Scale bars are shown.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "F Representative images of hematoxylin-eosin-stained Tsc2-deficient 105K tumors treated with rapamycin alone or rapamycin combinations. With the addition of a second drug to rapamycin, tumors more frequently tended to show glandular differentiation and less atypia. Scale bars are shown.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "C, AltFUS (arrow) endogenous expression in Human tissues (brain, muscles and kidney - 100 μg), in HEK293 and HeLa cultured cells (100 μg) and using the over-expression of altFUS CDS in HEK293 cells (50 μg) as positive control (representative image from n=3). The asterisk indicates a protein species detected with the anti-altFUS antibody specifically in the brain.",
    "ncbi_link": "altFUS: "
  },
  {
    "caption": "I, Endogenous altFUS mitochondrial expression in HEK293 cells following fractionation (representative image from n=3), with Tubulin as a marker of the cytosolic fraction and VDAC as a marker of the mitochondrial fraction. We used siFUS transfected cells as a negative control and altFUS transfected cells as a positive control for altFUS expression (WCL = Whole Cell Lysate, Cyto = Cytosol fraction, Mito = mitochondrial fraction).",
    "ncbi_link": "altFUS: 
FUS: 2521"
  },
  {
    "caption": "J, Representative images of the mitochondrial network (Tomm20 in red) in mock and altFUS-Flag (green) transfected HeLa cells (n=3). The white scale bar corresponds to 10μm. K, Proportion of tubules and globules in the mitochondrial network of mock HeLa cells and HeLa cells transfected with altFUS-Flag Quantification was done over a minimum of 100 cells across a technical duplicate per independent experiments (n=3, i.e. a minimum of 300 cells per biological conditions, p-value < 0.001, Mann-Whitney U test). The boxes extend to the 25th and 75th percentiles, with the median marked. The whiskers correspond to the 5th and 95th percentiles.",
    "ncbi_link": "altFUS: 
Flag: "
  },
  {
    "caption": "E, Scatter plot of the proteins identified by AP-MS indicating their enrichment (Fold-change over control) and their SAINT probability score. Proteins above the 0.8 threshold (grey line) are indicated in black, others in grey. AltFUS is indicated in red (bait) and preys known to regulate the autophagy or the cellular stress response are indicated in green.",
    "ncbi_link": "AltFUS: "
  },
  {
    "caption": "B, LC3-II accumulation after bafilomycin treatment from mock, altFUS, FUS, FUS(Ø), FUS-R495x, FUS(Ø)-R495x transfected cells and FUS(Ø)-R495x and altFUS co-transfected cells across 3 independent experiments (n=3, mean ± SD). The quantification corresponds to the treated/untreated ratio of LC3-II abundance Statistical significance is relative to the mock condition unless otherwise indicated (**** = p value < 0.0001, *** = p value < 0.001, ** = p value < 0.01, n.s. = non-significant, two-way ANOVA with Tukey's multiple comparison correction).",
    "ncbi_link": "altFUS: 
FUS: 2521"
  },
  {
    "caption": "D-E, Quantification of FUS cytoplasmic granules, number (D) and area (μm2) (E) in cells over-expressing the bicistronic (+) or monocistronic (-) construct for FUS, FUS-G156E, FUS-R495x, FUS-K510E, FUS-Q519x, FUS-Q519I-fs527x, FUS-R521C, and FUS-P525L. Statistical comparisons are made between bicistronic and monocistronic versions of each construct (n=3 - biological replicates, mean ± SD, **** = p value < 0.0001, *** = p value < 0.001, ** = p value < 0.01, * = p value < 0.05, n.s. = non-significant, one-way ANOVA test with Sidak's multiple comparison).",
    "ncbi_link": "FUS: 2521"
  },
  {
    "caption": "C-E, Locomotion assay represented by the percentage of climbing success in control and RU-486-treated transgenic Drosophila expressing mCherry or altFUS (C), the bicistronic FUS or the monocistronic FUS(Ø) (D), and the bicistronic FUS-R495x or the monocistronic FUS(Ø)-R495x (E) at day 1, 10 and 20 post-induction. Statistical comparisons were made between each population (n=4 - biological replicates). Indicated significance is between the monocistronic and the bicistronic transgenic flies of the RU-486-treated population (mean ± SD, n.s. = non-significant, * = p value < 0.05, *** = p value < 0.001, two-way ANOVA with Tukey's multiple comparison correction).",
    "ncbi_link": "altFUS: 
mCherry: 
FUS: 2521"
  },
  {
    "caption": "A, Graphical representation of FUS synonymous mutations (yellow) found in ALS patients. The canonical FUS mRNA is represented in dark blue (ENST00000254108 or NM_004960). The FUS protein coding sequence is indicated in light blue, and the altFUS protein coding sequence is indicated in green. B, Images by confocal microscopy of TDP-43 (white), FUS (GFP tagged - green) and altFUS (Flag tagged - red) in HeLa cells over-expressing GFP-FUS(Flag), GFP-FUS(P31L-Flag)-S44=, GFP-FUS(A38V-Flag)-G51=, GFP-FUS(A46V-Flag)-G59=, GFP-FUS(R64P-Flag)-S77= (representative images from n=3). White arrows indicate some TDP-43 aggregates. The white scale bar corresponds to 10 μm. C, Quantification of cells with TDP-43 aggregates in HeLa cells (see panel B). The data are represented as the fold-change compared to the GFP-FUS(Flag) expressing cells. Statistical significance is indicated above the bars (n=3 - biological replicates, mean ± SD, **** = p value < 0.0001, two-way ANOVA with Tukey's multiple comparison correction). ",
    "ncbi_link": "Flag: 
GFP: 
FUS: 2521"
  },
  {
    "caption": "A, B. Comparisons of RNAseq and ChIPseq data. Wt strain (A) and ∆rnjA (B). The x-axis shows the relative RNAP occupancy at a given gene (normalized ChIPseq coverage). The y-axis shows the relative abundance of the transcript (normalized RNAseq coverage; each dot is one gene). The genes are color-coded, ranging from yellow (low RNA abundance) to red (high RNA abundance) in wt. The ∆rnjA strain has higher RNAP occupancy mainly among the genes with less abundant transcripts. The color coding in (B) reveals no dramatic overall changes in the vertical direction (RNA abundance). If anything, some of the low abundance transcripts decreased further in level in the mutant strain. The main difference (mostly among the low abundance transcripts) is their shift in the horizontal direction to the right (towards higher occupancy with RNAP). Data represent mean values of three independent experiments.",
    "ncbi_link": "rnjA: 939483"
  },
  {
    "caption": "C. Relative expression of all sigma factors in wt (LK1371) versus ΔrnjA (LK1381). Wt levels of each sigma factor were set as 1 (indicated with the horizontal line).",
    "ncbi_link": "rnjA: 939483"
  },
  {
    "caption": "D. Sigma-dependent genes and correlation with expression of sigma factors (significantly changed) in ΔrnjA (LK1381). The most down-regulated sigma factor was sigD and almost all sigD-dependent genes were downregulated. A similar trend is visible for the rest of sigma factors and their respective dependent genes. The x-axis shows expression of each sigma factor, the y-axis shows expression of genes for each sigma regulon. The violet (dark blue) line: regression line.",
    "ncbi_link": "rnjA: 939483
sigD: 938482"
  },
  {
    "caption": "Average gene profiles of normalized RNA-seq and RNAP ChIPseq coverages from wt (solid lines) and ∆rnjA (dashed lines) strains were plotted for gene classes I-IV (n = 762, 315, 553 and 1654 genes, respectively). Open reading frames were rescaled to 1 kb, upstream and downstream regions of 0.2 kb were also included in the plots. Data represent mean values of 3 independent experiments. The pie-chart shows the overall distribution of class I-IV and other genes.",
    "ncbi_link": "rnjA: 939483"
  },
  {
    "caption": "B. Relative expression (mRNA) of helD, mfd, rho, greA, nusA, nusB, and nusG in the ∆rnjA strain (normalized to wt [set as 1]).",
    "ncbi_link": "greA: 937565
helD: 936037
mfd: 936653
nusA: 939628
nusB: 938606
nusG: 936851
rho: 937042
rnjA: 939483"
  },
  {
    "caption": "(D) Representative fluorescence images of SCG neurons from neonatal mice (age P5-7) electroporated with plasmids coding for mCherry and for siRNA targeting STIM1. Neurons were cooled from 35°C to 7°C in the presence of 100μM verapamil. Electroporation was indicated by expression of mCherry (# in left-hand panel); in these neurons a cold response was absent (# in right-hand panel) while in neurons not expressing mCherry (*) cold responses were still observed. Scale bar 20μm.",
    "ncbi_link": "mCherry: 
STIM1: 20866"
  },
  {
    "caption": "(A) Representative TIRF microscopy images (imaging depth 100nm) showing that cooling from 35°C to 13°C increases ORAI1 puncta formation and colocalization of ORAI1 with STIM1 in HEK293 cells transfected with ORAI1-CFP and STIM1-YFP. Cooling to 13°C causes the appearance of new ORAI1 puncta (examples shown by *) that are not present in the 35°C image and are colocalised with STIM1. Cooling also causes STIM1 to move towards the cell surface in edge-on views (arrows). To reduce cell motility, the experiment was conducted in nominal 0[Ca]e, which potentially caused partial formation of STIM1 puncta before the images shown. Scale bar = 5μm. Temperature trace shown below. Mean fluorescence intensity adjusted to compensate for increase in intrinsic fluorescence of CFP and YFP caused by cooling (see Fig. S12).",
    "ncbi_link": "CFP: 
YFP: 
ORAI1: 84876
STIM1: 6786"
  },
  {
    "caption": "Schematic representation of the upstream region of myogenin and amplified regions by RT-PCR (top). RT-PCR for the novel transcripts at the upstream region of myogenin in C2C12 myotubes (bottom). The presence or absence of reverse transcriptase (RT) is shown by (+) or (-), respectively. The templates (cDNA or genomic DNA) are indicated by C or G, respectively.",
    "ncbi_link": "myogenin: 17928"
  },
  {
    "caption": "The primers used for RT-PCR (top). Strand-specific RT-PCR for the novel transcripts at the upstream region of myogenin in C2C12 myotubes using total RNA (middle and bottom) and poly(A)+ RNA (bottom).",
    "ncbi_link": "myogenin: 17928"
  },
  {
    "caption": "Chromatin pellet extract (CPE)/soluble nuclear extract (SNE) ratio of SRA1, Malat1, and Myoparr in C2C12 myotubes on a log scale. n = 3, mean ± SD.",
    "ncbi_link": "Malat1: 72289
Myoparr: 114004354
SRA1: 24068"
  },
  {
    "caption": "Quantitative RT-PCR for myogenin (A) and Myoparr (B) during myogenesis of C2C12 cells, primary mouse myoblasts (growth medium, GM), and mouse embryonic skeletal muscle (S.K.). The x-axis shows days after differentiation induction or embryonic days. n = 3, mean ± SD.",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "qRT-PCR showing increased Myoparr expression by MyoD in C3H10T1/2 fibroblasts. n = 4, mean ± SD. **p < 0.01 (unpaired two-tailed Welch's t-test).",
    "ncbi_link": "MyoD: 17927
Myoparr: 114004354"
  },
  {
    "caption": "Treatment of recombinant TGF-β for 24 h decreased Myoparr expression in differentiating C2C12 cells. n = 3, mean ± SD. *p < 0.05 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Relative luciferase activities of the indicated promoter in differentiating C2C12 cells by exogenous MyoD. n = 3, mean ± SD. **p < 0.01. (unpaired two-tailed Student's t-test).",
    "ncbi_link": "MyoD: 17927"
  },
  {
    "caption": "C2C12 cells were transfected with 50 nM of indicated siRNAs in growth medium. After additional 24-h incubation in growth medium, cells were transferred to differentiation medium. The levels of Myoparr and myogenin expression were quantified by qRT-PCR 24 h after differentiation induction. n = 3, mean ± SD. *p < 0.05. n.s., not significant. Statistical analyses were performed using unpaired two-tailed Student's t-test. In cases of unequal variances, unpaired two-tailed Welch's t-test was used.",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Western blot showing decreased expression of myogenin in differentiating C2C12 cells 48 h after Myoparr KD. Tubulin expression served as an internal control.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "The expression levels of myogenin and Myoparr evaluated by qRT-PCR in myogenin-depleted C2C12 cells. n = 3, mean ± SD. **p < 0.01. ***p < 0.001 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "ChIP-qPCR detection of Pol II occupancy and histone modification status at the myogenin locus in Myoparr-depleted differentiating C2C12 cells. The data were normalized to input values. n = 3, mean ± SD. *p < 0.05. **p < 0.01 (unpaired two-tailed Student's t-test or unpaired two-tailed Welch's t-test).",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Retrieval rate of Myoparr using Myoparr-ChIRP probes from C2C12 cells quantified by qPCR is shown as percent of input values. GAPDH was amplified as a negative control. n = 3, mean ± SD. ND, not detected.",
    "ncbi_link": "GAPDH: 
Myoparr: 114004354"
  },
  {
    "caption": "ChIRP-qPCR detection of the interaction between endogenous Myoparr and the myogenin promoter. The myogenin 3´UTR and GAPDH promoter were amplified as negative controls. The data were normalized to input values. n = 3, mean ± SD. *p < 0.05. ** p < 0.01 (unpaired two-tailed Welch's t-test). ND, not detected.",
    "ncbi_link": "GAPDH: 
myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Immunocytochemistry for the detection of myogenin at 24 h (G) or MHC at 72 h (H) in Myoparr-depleted C2C12 cells after differentiation induction. Nuclei were counterstained with DAPI. Bar, 100 μm. The percentage of myogenin-positive cells or fusion index is shown as percent of the control. n = 3, mean ± SD. **p < 0.01. ***p < 0.001 (unpaired two-tailed Student's t-test or unpaired two-tailed Welch's t-test).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Genes significantly differentially expressed in both Myoparr- and myogenin-depleted cells show correlated expression (R = 0.63, log 2 ratio scale).",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Following immunoprecipitation, the interaction between Myoparr and endogenous Ddx17 was confirmed by immunoblotting using a Ddx17-specific antibody. Two different Ddx17 isoforms (p72 and p82) were observed.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Determination of the Ddx17-binding region of Myoparr by RNA pull-down analyses. Schematic diagram of full-length or truncated Myoparr used for RNA pull-down (top). In vitro transcribed/translated Ddx17 protein was pulled down by indicated Myoparr and then detected by western blot using a Ddx17 antibody (bottom).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Relative luciferase activities of indicated constructs in differentiating C2C12 cells transfected with control or Myoparr shRNA (Myoparr KD).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Significantly decreased MHC expression in Ddx17-depleted C2C12 cells is shown by immunocytochemistry. Nuclei were counterstained with DAPI. Bar, 100 μm. Fusion index is shown as percent of the control. n = 3, mean ± SD. **p < 0.01 (unpaired two-tailed Student's t-test). Immunocytochemistry for myogenin in Ddx17-depleted C2C12 cells. Bar, 100 μm. Myogenin-positive cells are shown as percent of the control. n = 4, mean ± SD. **p < 0.01 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "Ddx17: 67040"
  },
  {
    "caption": "Relative luciferase activities of the -1650-Luc by the combination of MyoD and Ddx17 or Ddx17 mutant (K142R). Bars indicate the average of two independent experiments, and open circles represent the values of each experiment.",
    "ncbi_link": "Ddx17: 67040
MyoD: 17927"
  },
  {
    "caption": "Ddx17 or Ddx17 mutant (K142R) was pulled down by full-length Myoparr and then detected by western blot.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Reduced interaction between endogenous Ddx17 and PCAF in Myoparr-depleted C2C12 cells. After Myoparr KD, the cell lysates were subjected to immunoprecipitation (IP) with a Ddx17-specific antibody 36 h after differentiation induction (right panel). Each lysate was loaded as an input (left panel). Relative quantification of (E) is shown as IP/input ratio. n = 3, mean ± SD. *p < 0.05. n.s., not significant (unpaired two-tailed Student's t-test).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Increased interaction between Ddx17 and PCAF by Myoparr. PCAF protein was pulled down by 3×Flag-Ddx17 in the presence or absence of Myoparr using a Flag antibody and then detected by western blot.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "ChIP-qPCR detection of Ddx17 (H) and PCAF (I) occupancies at the myogenin locus in Myoparr-depleted differentiating C2C12 cells. The data were normalized to input values. n = 3, mean ± SD. *p < 0.05 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Heatmap displaying expression changes of 754 genes significantly altered either in Myoparr- or Ddx17-depleted cells (log 2 ratio scale).",
    "ncbi_link": "Ddx17: 67040
Myoparr: 114004354"
  },
  {
    "caption": "Genes significantly differentially expressed in both Myoparr- and Ddx17-depleted cells show correlated expression (R = 0.94, log 2 ratio scale).",
    "ncbi_link": "Ddx17: 67040
Myoparr: 114004354"
  },
  {
    "caption": "Myoparr and Ddx17 are required for C2C12 cell cycle withdrawal. C2C12 cells transfected with each siRNA were cultured in growth medium for 24 h. After differentiation induction, cells were maintained in differentiation medium for 40 h and then treated with EdU for 6 h. EdU-positive cells are shown as percent of the control. Nuclei were counterstained with Hoechst 33342. n = 3, mean ± SD. **p < 0.01 (unpaired two-tailed Student's t-test). Bar, 100 μm.",
    "ncbi_link": "Ddx17: 67040
Myoparr: 114004354"
  },
  {
    "caption": "qRT-PCR for pri-miR-133b, pri-miR-206, and H19 expression in differentiating C2C12 cells transfected with indicated siRNAs. n = 3, mean ± SD. *p < 0.05. **p < 0.01.",
    "ncbi_link": "H19: 14955
pri-miR-133b: 723817
pri-miR-206: 387202"
  },
  {
    "caption": "ChIP-qPCR detection of Pol II occupancy at the indicated promoters in Myoparr-depleted C2C12 cells. The data were normalized to input values. n = 3, mean ± SD. *p < 0.05. Myoparr KD decreased Pol II occupancy at the miR-133b promoter with a marginal trend toward significance (p = 0.052).",
    "ncbi_link": "miR-133b: 723817
Myoparr: 114004354"
  },
  {
    "caption": "ChIP-qPCR detection of Ddx17 (C) occupancies at the indicated promoters in Myoparr-depleted C2C12 cells. n = 3, mean ± SD. *p < 0.05. **p < 0.01.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "ChIP-qPCR detection of PCAF (D) occupancies at the indicated promoters in Myoparr-depleted C2C12 cells. n = 3, mean ± SD. *p < 0.05. **p < 0.01.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "qRT-PCR showing decreased expression of miR-133b and miR-206 in both Myoparr- and Ddx17-depleted C2C12 cells. n = 3, mean ± SD. *p < 0.05. **p < 0.01.",
    "ncbi_link": "Ddx17: 67040
miR-133b: 723817
miR-206: 387202
Myoparr: 114004354"
  },
  {
    "caption": "Western blots showing increased ERK1/2 activity (pERK1/2) and Cdc6 expression in differentiating C2C12 cells 48 h after Myoparr and Ddx17 KD. Tubulin expression served as an internal control.",
    "ncbi_link": "Ddx17: 67040
Myoparr: 114004354"
  },
  {
    "caption": "Increased Pola1 expression detected by qRT-PCR. n = 3, mean ± SD. **p < 0.01.",
    "ncbi_link": "Pola1: 18968"
  },
  {
    "caption": "Expression of myogenin in innervated and denervated TA muscles detected by qRT-PCR 7 d after denervation. n = 4, mean ± SD. ***p < 0.001 (unpaired two-tailed Welch's t-test). qRT-PCR showing increased Myoparr expression in denervated TA muscles 7 d after denervation. n = 3, mean ± SD. ***p < 0.001 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "myogenin: 17928
Myoparr: 114004354"
  },
  {
    "caption": "Immunoblot showing decreased expression of myogenin by Myoparr depletion in denervated TA muscle 7 d after denervation. Expression of tubulin served as an internal control.",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Weights of innervated and denervated TA muscles electroporated either with control or Myoparr shRNA. Muscle weights were measured 7 d after denervation. n = 5 for each group, mean ± SEM. ***p < 0.001. n.s., not significant (unpaired two-tailed Student's t-test).",
    "ncbi_link": "Myoparr: 114004354"
  },
  {
    "caption": "Representative immunostaining images for laminin (red) and EmGFP (green) of innervated or denervated TA muscles electroporated with control or Myoparr shRNA, both containing EmGFP. Bar, 100 μm.",
    "ncbi_link": "EmGFP: 
Myoparr: 114004354"
  },
  {
    "caption": "B-C. (B) Micronuclei frequency formation by live cell imaging in untreated (NT) and Auxin-treated (IAA) condition. (C) Bar graph represents the type of chromosome mis-segregation (independently of the dCas9 signal) observed in the indicated conditions, with (IAA) or without (NT) auxin, in the cell lines expressing dCas9 mScarlet-I and sgRNA targeting chromosome 1 or 3. Error bars represent the SEM of four independent experiments in which cells labeled for chromosome 1 and 3 were analyzed together (n = 45 - 149 cells).",
    "ncbi_link": "mScarlet-I: 
Cas9: 901176"
  },
  {
    "caption": "D. Representative live cell imaging of RPE-1 cells dCas9 mScarlet-I with sgRNA targeting chromosome 1 (red dots) starting from metaphase and showing example of correct (untreated) or mis-aligned chromosome (auxin) leading to the formation of a micronucleus. Yellow arrows mark mis-aligned- and micronucleus-containing chromosome 1. Cells were imaged every five minutes. The numbers indicate the time point at which the presented images were taken. Cells were fixed at the end of the movie to detect Cas9 with an antibody. Scale bar represents 10 µm.",
    "ncbi_link": "mScarlet-I: 
Cas9: 901176"
  },
  {
    "caption": "E. Bar graph representing the proportion of chromosome mis-segregation observed in both cell lines after auxin addition. Only movies in which the dCas9 mScarlet-I dots were clearly visible during the whole division were taken into consideration for the analysis (N = 6 - 10 cells).",
    "ncbi_link": "mScarlet-I: 
Cas9: 901176"
  },
  {
    "caption": "B. Representative image of centromere 11 (red) and centromere X (green) FISH on RPE-1 CENP-AAID CENP-B KO mutant in control (top) or IAA treated condition (bottom). Scale bar represents 5 µm. Bar graphs show automatic FISH quantification of chromosome mis-segregation in the indicated cell lines with and without IAA addition for 24 h. Error bars represent the SEM of three independent experiments (n> 200 cells per experiment). Dunnett's multiple comparisons test was used to compare conditions. Grey lines separate independent experiments. Fold changes between grey and red bars are also indicated.",
    "ncbi_link": "CENP-A: 1058
CENP-B: 1059"
  },
  {
    "caption": "K. (Left) Representative image of CENP-B box (red) staining after siRNA against CENP-A/HJURP for 48 h. CENP-B box signals at individual micronuclei are magnified in insets. Scale bar represent 5 µm. (Right) Bar graph represents the mean of the CENP-B box FISH intensity contained in the main nucleus versus the one present in the micronucleus ± SEM. Color dots represent independent experiments. (n > 43 micronuclei and 840 main nucleus) Mann-Whitney U test: ***p = 0.0001.",
    "ncbi_link": "CENP-A: 12615
HJURP: 381280"
  },
  {
    "caption": "(c) Western blot showing typical efficiency of FLCN knockdown in HeLa cells using a pool consisting of 4 oligonucleotides and 2 independent oligonucleotides from the pool. Graph shows relative FLCN expression (n=3, error bars show S.E.M.)",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(d) Representative confocal fluorescence microscopy images showing LAMP1 (magenta) distribution in HeLa cells under normal growth or starvation conditions in cells depleted of FLCN or control cells transfected with a non-targeting siRNA. The location of the Golgi (green) is highlighted by giantin staining.(e) Schematic illustrating application of the cumulative intensity distribution method for quantification of lysosome distribution.(f) Graph showing cumulative distribution of LAMP1 intensity in normal growth and starvation conditions in HeLa cells. P-value is determined by the extra sum of F-squares test following non-linear regression and curve fitting. Error bars show S.E.M. from 30 cells in 3 replicates.(g) Graph showing cumulative distribution of LAMP1 intensity in starvation conditions for control cells transfected with non-targeting siRNA or cells depleted of FLCN. Error bars show S.E.M. from 30 cells in 3 replicates.",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(a) Graphs showing cumulative distribution of LAMP1 intensity in control GFP (black), GFP-Rab34 (green) or GFP-Rab7 (blue) transfected cells. Note black line and symbols partially obscure blue.",
    "ncbi_link": "Rab34: 19376
Rab7: 7879///338382"
  },
  {
    "caption": "(c) Representative confocal fluorescence microscopy images of FLCN depleted or control cells, transfected with GFP-Rab34. Scale bar = 10μm.",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(d) (left) Graphs showing mean GFP-Rab34 expression (grey values) and cumulative distribution of LAMP1 intensity (right) in FLCN depleted or control siRNA cells transfected HeLa cells expressing GFP-Rab34. Error bars show S.E.M.. from 30 cells in 3 replicates. Scale bar = 10μm.",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(e) Western blot and graph showing typical efficiency of Rab34 siRNA knockdown after 48 hours in HeLa cells. Error bars show S.E.M from 3 experiments, *** = p<0.001.",
    "ncbi_link": "Rab34: 19376"
  },
  {
    "caption": "(f) Representative confocal fluorescence microscopy images showing LAMP1 (magenta) distribution in HeLa cells under normal growth or starvation conditions in cells depleted of Rab34 or control cells transfected with a non-targeting siRNA. Giantin is shown in green. Scale bar = 10μm.(g) Graphs showing cumulative distribution of LAMP1 intensity in normal growth or starvation conditions for control cells or cells depleted of Rab34 using siRNA.(h) Graph showing percentage of LAMP1 in cis-medial Golgi-region (giantin overlap) in the indicated conditions. Error bars show S.E.M from 30 cells in 3 replicates, *** = p<0.001.",
    "ncbi_link": "Rab34: 19376"
  },
  {
    "caption": "(d) Analysis of Lysotracker-Red dynamics using PCC decay in HeLa cells transfected with either GFP or GFP-Rab34. Data is from 10 cells per condition. Error bars show S.E.M.",
    "ncbi_link": "Rab34: 19376"
  },
  {
    "caption": "(d) Western blot analysis of GST-RILP pull down from UOK257 cells showing DENN domain dependent association of FLCN with RILP N-terminal, Rab binding domain (RBD) and C-terminal fragments.",
    "ncbi_link": "FLCN: 201163
RILP: 83547"
  },
  {
    "caption": "(f) Western blot analysis of GST-RILP pull down showing direct interaction between RILP and GTP hydrolysis deficient (Q111L) Rab34 (at 200nM, in the presence of 1mM GTPγS) and FLCN-DENN domain (1μM), but not low nucleotide affinity (T66N) Rab34. FLCN-DENN enhances association of RILP with Q111L Rab34. Graph shows quantification of relative RILP / Rab34 Q111L binding. Error bars show SEM. ** = p<0.01.",
    "ncbi_link": "FLCN: 201163
Rab34: 19376"
  },
  {
    "caption": "(d) Western blot showing FLCN and FLCNΔDENN expression in stable UOK257 derived cell lines.",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(e) Representative widefield fluorescence microscopy images showing intracellular distribution of LAMP1 in UOK257, UOK257-FLCN and UOK257-FLCNΔDENN cells. Scale bar = 10μm. Graphs showing cumulative distribution of LAMP1 intensity in UOK257, UOK257-FLCN and UOK257-FLCNΔDENN cells. Error bars show S.E.M from 30 cells in 3 replicates.",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "(f) (left) Western blot showing endogenous Rab7 and Rab34 expression in UOK257, UOK257-FLCN and UOK257-FLCNΔDENN cells and relative levels of activity as measured by GST-RILP pull down. HSC70 is used as a loading control. (right) Graphs show quantification of bound Rab7/Rab34 from 3 independent experiments (p<0.05, *** = p<0.001).",
    "ncbi_link": "FLCN: 201163"
  },
  {
    "caption": "A. Representative pseudocolor images of PC6 cells transfected with EYFP-Parkin (green) and mitochondrially targeted CFP (red) with and without PINK1 and Miro1 shRNA and Miro2 shRNA. Zoomed images show translocation of EYFP-Parkin to mitochondria in PINK1-overexpressing PC6 cells",
    "ncbi_link": "PINK1: 298575
Parkin: 5071
Miro1: 303351
Miro2: 287156"
  },
  {
    "caption": "B. Quantification of EYFP-Parkin translocation to mitochondria. The percentage of PC6 cells with EYFP-Parkin translocated to mitochondria in response to PINK1 overexpression is lower in the Miro shRNAs-expressing groups when compared with the scrambled shRNA-expressing group (scr shRNA). ****P < 0.0001, n = 6 dishes per group, 20 fields per dish, one-way ANOVA",
    "ncbi_link": "PINK1: 298575
Miro: 303351"
  },
  {
    "caption": "C. The kinetics of EYFP-Parkin translocation is different in PC6 cells transfected with scrambled or Miro shRNAs. Cells were plated in separate compartments of the same dish, enabling us to visualize Parkin translocation simultaneously over 3 h under similar conditions in response to antimycin with oligomycin treatment (A&O, both 10 µM). The spatial heterogeneity of EYFP-Parkin (coefficient of variation of the intensity of individual pixels) was estimated for individual cells for each time point (n = 39-47 cells; P < 0.0001 difference between the curves P < 0.0001, two-way ANOVA; lines show mean, dashed area shows SEM)",
    "ncbi_link": "Miro: 303351"
  },
  {
    "caption": "D. Miro shRNAs mitigate the effect of A&O on EYFP-Parkin translocation. PC6 cells transfected with EYFP-Parkin with and without Miro shRNAs were treated with DMSO or A&O (both 10 µM) for 3h. The figure demonstrates that the percentage of cells with Parkin translocated to mitochondria was lower in the Miro shRNAs-expressing group when compared with the scrambled shRNA-expressing group. ****P < 0.0001, n = 4 dishes, 20 fields per dish, one-way ANOVA",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "E. Miro shRNAs inhibit PINK1-induced mitophagy in PC6 cells. The figure shows the changes in the excitation spectra of mitochondrially targeted pH-sensitive Keima (ratio of 561 nm/458nm fluorescence intensities). ****P < 0.0001, n = 80 cells from 4 dishes, Kruskal-Wallis test",
    "ncbi_link": "Miro: 303351"
  },
  {
    "caption": "F. Miro shRNAs inhibit basal mitophagy in primary cortical neurons expressing mitochondrially targeted Keima. Mitochondria in lysosomes (acidic pH) were counted manually, by a blinded observer (**P < 0.01, n = 9 dishes, 9 fields per dish, from 2 independent experiments, one-way ANOVA)",
    "ncbi_link": "Miro: 303351"
  },
  {
    "caption": "G. Miro shRNAs decrease the number of mitochondria co-localised with the autophagosome marker EGFP-LC3B in primary cortical neurons (**P < 0.01, n = 5 dishes, 9 fields per dish, one-way ANOVA).",
    "ncbi_link": "Miro: 303351"
  },
  {
    "caption": "A. The pattern of Parkin translocation caused by Miro1 overexpression is different from A&O-induced translocation. The figure illustrates puncta-like EYFP-Parkin on mitochondria in antimycin and oligomycin-treated (both 10 µM for 3h) PC6 cells (middle panels), whereas in Miro1-overexpressing cells, EYFP-Parkin appears along rod-shaped mitochondria visualised with CFP-mito (lower panels). The merged panels present EYFP-Parkin (green) and CFP-mito (red)",
    "ncbi_link": "Miro1: 303351"
  },
  {
    "caption": "B. Overexpression of myc-Miro1 and untagged Miro2, but not myc-Miro2, induce EYFP-Parkin translocation to mitochondria. ****P < 0.0001 vs control group, n = 5-6 dishes, 20 fields per dish, one-way ANOVA or t-test",
    "ncbi_link": "Miro1: 55288
Miro2: 89941"
  },
  {
    "caption": "C. Quantification of EYFP-Parkin signal heterogeneity in PC6 cells demonstrates that Miro1 overexpression induces Parkin translocation from the cytosol to mitochondria, which is significantly weaker than PINK1 overexpression- or A&O (3 h)-induced translocation. **P < 0.01 and ****P < 0.0001 vs control group, n = 18-32 cells from 3 dishes per group, Kruskal-Wallis test",
    "ncbi_link": "PINK1: 298575
Miro1: 303351"
  },
  {
    "caption": "Miro1 overexpression does not cause mitochondrial depolarization (D) Representative image of Miro1 and EYFP-Parkin-transfected cells stained with TMRE. The merged panels present EYFP-Parkin (green) and TMRE (red)",
    "ncbi_link": "Parkin: 5071
Miro1: 303351"
  },
  {
    "caption": "Miro1 overexpression does not cause mitochondrial depolarization (E) Relative TMRE intensity quantified in neurons transfected with Miro1 (detected by CFP-mito co-transfection); the control group is non-transfected cells in the same image. The relative TMRE signal was slightly increased in Miro1 overexpressing neurons but unaffected in Miro shRNAs-expressing neurons. Note that FCCP treatment (3 μM for 15 min) almost completely abolished TMRE fluorescence. ****P < 0.0001 vs control group, n = 94-186 cells from 4 dishes per group, Kruskal-Wallis test",
    "ncbi_link": "Miro: 303351
Miro1: 303351"
  },
  {
    "caption": "F. Co-expression of HA-Parkin with Miro1 does not suppress mitochondrial motility in axons of cortical neurons. Overexpression of Miro1 alone increased the motion time in both directions as well as the relative mitochondrial velocity. Co-transfection of Parkin did not affect significantly the motility parameters. Data are presented as Tukey boxplot. *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001, n = 689-846 individual mitochondria from 39-44 axons per group pooled from at least from 10 individual dishes from 4 independent experiments, Kruskal-Wallis test",
    "ncbi_link": "Parkin: 5071
Miro1: 303351"
  },
  {
    "caption": "G. Parkin overexpression does not induce degradation of myc-Miro1 in control conditions. Representative Western blot image and analysis of myc-Miro1 expression in HEK cells. Treatment with A&O (both 15 µM) for 3h in the absence of MG132 led to slight degradation of myc-Miro1. Co-expression of EYFP-Parkin did not induce degradation of Miro1 although an additional band above the Miro1 band was present. However, Parkin co-expression enhanced Miro1 degradation when cells were treated with A&O. *P < 0.05 and ****P < 0.0001, ns: not significant, n = 4 independent experiments, one way ANOVA. Note that only the main band of myc-Miro1 at 80 kDa was analysed and that YFP was used to compensate in groups not expressing EYFP-Parkin",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "A. Miro1 induces EYFP-Parkin translocation in the presence of PINK1 shRNA. PC6 cells were transfected with EYFP-Parkin and Miro1 or treated for 3h with A&O (both 10 µM) in the presence of scrambled shRNA or PINK1 shRNA. Miro1 induced Parkin translocation also in the presence of PINK1 shRNA while A&O treatment did not. ****P < 0.0001 compared with the respective control group, n = 5-6 dishes, 20 fields per dish, one-way ANOVA",
    "ncbi_link": "PINK1: 298575
Parkin: 5071
Miro1: 303351"
  },
  {
    "caption": "B. Miro1 induces EYFP-Parkin translocation in PINK1 -/- MEFs. MEFs obtained from PINK1 +/+ and -/- mice were transfected with EYFP-Parkin and Miro1 or treated with A&O (both 10 µM for 3h). Miro1 induced Parkin translocation in both MEF lines but A&O only in PINK1 +/+ MEFs. ****P < 0.0001 compared with respective control group, n = 6 dishes, one-way ANOVA",
    "ncbi_link": "PINK1: 68943
Parkin: 5071
Miro1: 59040"
  },
  {
    "caption": "C. Mutated EYFP-Parkin is recruited to mitochondria in response to Miro1 overexpression. PC6 cells were transfected with wild type, T240R or C431N EYFP-Parkin and Miro1 or treated for 3 hours with A&O (both 10 µM). Miro1 induced translocation of all EYFP-Parkin mutants whereas A&O treatment was not able to induce equivalent translocation of Parkin mutants. **P < 0.01 and ****P < 0.0001 compared with respective control group, n = 3-6 dishes, 20 fields per dish, one-way ANOVA",
    "ncbi_link": "Parkin: 5071
Miro1: 303351"
  },
  {
    "caption": "D. Parkin mutants T240R and C431N interact with Miro1 both in DMSO- or A&O-treated (both 15 µM for 3h) HEK cells. Note that the higher molecular weight bands of Miro1 were observed only in WT Parkin-expressing groups.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "A. Miro1 K572R mutant interacts with HA-Parkin similarly to Miro1 WT. HEK cells overexpressing myc-Miro1 WT or K572R mutant were treated with DMSO (control) or A&O (both 15 µM) for 3 hrs. Myc-Miro1 was immunoprecipitated and probed for myc-Miro1 and HA-Parkin. Note the diminished degradation of Miro1 K572R in input and the additional band above Miro1 WT in the IP, which is missing in the case of the K572R mutant",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "B. Miro1 K572R ubiquitination by Parkin is reduced. HEK cells overexpressing HA-ubiquitin, myc-Miro1 or myc-Miro1 K572R and EYFP-Parkin were treated with DMSO (control) or A&O (both 15 µM) for 3 hrs. HA-ubiquitin was immunoprecipitated and probes were immunoblotted for ubiquitin-HA and myc-Miro1",
    "ncbi_link": "Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "C. Representative images of PC6 cells overexpressing Miro1 K572R or Miro1 WT together with EYFP-Parkin. K572R mutant induces Parkin translocation similar to WT in basal conditions but not after treatment with A&O (both 7.5 µM) for 3 hours. Note the spatial heterogeneity values shown in the images",
    "ncbi_link": "Parkin: 5071
Miro1: 303351"
  },
  {
    "caption": "D. Quantification of EYFP-Parkin signal heterogeneity in PC6 cells demonstrates that WT Miro1 overexpression amplifies Parkin translocation in response A&O (both 7.5 µM) treatment for 3 hours, but K572R mutation of Miro1 abolishes this effect. ***P < 0.001 and ****P < 0.0001, n = 152-172 cells from 3 dishes per group, Kruskal-Wallis test. Data are presented as means ± SEM.",
    "ncbi_link": "Miro1: 303351"
  },
  {
    "caption": "A. A Ca2+-insensitive mutant of Miro1 (Miro1-EF) interacts with Parkin. HEK cells overexpressing myc-Miro1 or myc-Miro1-EF and EYFP-Parkin were treated with DMSO (control) or A&O (both 15 µM) for 3 hrs. Myc-Miro1 was immunoprecipitated and probes were immunoblotted for Miro1 (red) and Parkin (green). The high-contrast grayscale image from the green channel of this blot shows that endogenous Parkin co-immunoprecipitated with Miro1 in all conditions. The bar chart shows the quantification of co-immunoprecipitated Parkin EYFP from 4 different blots normalised to total EYFP-Parkin signal (*P < 0.05 and **P < 0.01, repeated measures ANOVA",
    "ncbi_link": "Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "B. Miro1-EF is less susceptible to ubiquitination by Parkin. HEK cells overexpressing HA-ubiquitin, myc-Miro1 or myc-Miro1-EF and EYFP-Parkin were treated with DMSO (control) or A&O (both 15 µM) for 3 hrs. HA-ubiquitin was immunoprecipitated and probes were immunoblotted for ubiquitin (red), Miro1 (green) and Parkin (green; representative images are from the same experimental material on separate SDS-PAGE-WB membranes). The high-contrast grayscale shows the green channel of this blot, and the bar chart shows quantification of co-immunoprecipitated Miro from 3 different blots (**P < 0.01 and ***P < 0.001, repeated measures ANOVA). Note that EYFP-Parkin co-immunoprecipitated with ubiquitin only after A&O treatment",
    "ncbi_link": "Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "C. Mutation of Miro1 EF-hands diminishes Miro1 ubiquitination with S65-phosphorylated ubiquitin. HEK cells were transfected with EYFP-Parkin with either myc-Miro1-WT or myc-Miro1-EF with or without PINK1-V5. Cells were treated with either DMSO or A&O (both 10 µM) for 5 hrs with the exception of the PINK1-V5 group. Myc-Miro1 was immunoprecipitated and probes were immunoblotted for Miro1 (red), S65-Phosphoubiquitin and PINK1-V5 (green; the weak bands marked with the asterisk are nonspecific).",
    "ncbi_link": "Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "A. Kinetics of EYFP-Parkin translocation in response to A&O is different in control and Miro1-EF-expressing PC6 cells. The inset shows how different compartments of the same dish were transfected with EYFP-Parkin and control plasmid or Miro1-EF and followed over 3 hrs using a confocal microscope after addition of A&O (both 10 µM). The graph shows the average spatial heterogeneity of EYFP-Parkin fluorescence, reflecting the ratio of mitochondrial-to-cytosolic Parkin over time (n = 40-43 cells, difference between the curves P < 0.0001, two-way ANOVA; lines show mean, dashed area shows SEM)",
    "ncbi_link": "Parkin: 5071
Miro1: 55288"
  },
  {
    "caption": "The percentage of cells where EYFP-Parkin translocates in response to A&O (both 10 µM, B is decreased in Miro1-EF-expressing PC6 cells. **P < 0.01, ****P < 0.0001 compared with the indicated group (n = 3-6 dishes, 20 fields per dish, one way ANOVA for",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "The percentage of cells where EYFP-Parkin translocates in response t PINK1 overexpression (C) is decreased in Miro1-EF-expressing PC6 cells. **P < 0.01, ****P < 0.0001 compared with the indicated group (n = 3-6 dishes, 20 fields per dis Welch\"s ANOVA f",
    "ncbi_link": "PINK1: 298575
Miro1: 55288"
  },
  {
    "caption": "D. Time course showing laser-induced EYFP-Parkin accumulation in the irradiated area of the neuronal soma of primary rat cortical neurons. Cells were transfected with CFP-mito and EYFP-Parkin and visualized using a confocal microscope. Mitochondria were irradiated in a 0.9 µm x 0.9 µm-frame using a 405-nm laser line (25 iterations using 100% laser power, pixel time 164 µs)",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "E, F Miro1-EF delays and reduces irradiation-induced EYFP-Parkin translocation. (E) The time course of translocation strength in control and Miro1-EF-expressing neurons. Difference between the curves P = 0.0016, two-way ANOVA. (F) Comparison at the 60-min time point (*P < 0.05, n = 6 dishes, at least 9 neurons per dish, t-test).",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "Treatment of neurons for 10 min with 100 μM glutamate/10 μM glycine led to excessive Ca2+ entry into the cytosol Glutamate-induced Ca2+ entry was not affected by Miro1 WT or Miro1 EF overexpression; n = 31-48 neurons per group; ns, Kruskal-Wallis test)",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "E, F Glutamate treatment (100 μM glutamate/10 μM glycine for 10 min) led to the appearance of a few Parkin-positive strong puncta co-localising with mitochondrial marker (white arrow), imaged 2.5 h after treatment (E). Further analysis demonstrated that the expression of Miro1-EF mutant decreased and Miro1 WT increased the number of neurons with EYFP-Parkin-positive mitochondria following glutamate treatment (F; n = 6-10; **P < 0.01 and ****P < 0.0001, one-way ANOVA)",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "G. Glutamate treatment (100 μM glutamate/10 μM glycine for 10 min) was associated with an increased number of mitochondrial co-localisation with the autophagosome marker EGFP-LC3B in neuronal soma at 5-6 h later, which was not observed in Miro1-EF-expressing neurons (n = 8 dishes; *P < 0.05, one-way ANOVA)",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "H. Glutamate treatment (30 μM glutamate and 1 μM glycine for 10 min) was also associated with a significant loss of mitochondrial density in axons at 6 h later, which was reversed by Miro1-EF but not by Miro1 WT (n = 60-90 axons from 6-9 dishes; **P < 0.01, ***P < 0.001 and ****P < 0.0001, Kruskal-Wallis test)",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "I. Glutamate treatment (100 μM glutamate and 10 μM glycine for 10 min) led to a decline, at 6-8 h, in cytosolic ATP measured using ATP/ADP sensor Perceval HR, which was reversed by Miro1-EF but not by Miro1 WT (n = 59-60 neurons from 6 dishes; **P < 0.01, Welch\"s A",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "J. Glutamate (100 μM glutamate and 10 μM glycine for 10 min) induced excitotoxicity (24 h after treatment) that was partially reversed by Miro1-EF but not by Miro1 WT. Data is presented as a percentage of control neuron count (n = 10 dishes; ***P < 0.001, repeated measures ANOVA).",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "A. Expression of endothelial Notch target genes in microvascular endothelial cells isolated from skeletal muscle of mice kept on control diet (CD, 10% fat, 70% carbohydrates) or high-fat diet (HFD, 60% fat, 20% carbohydrates) or high-fat and sugar diet (HFS, 60% fat, 20% carbohydrates and 42 g/l sucrose in drinking water). n=4, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Notch: 18132///18131///18129///18128"
  },
  {
    "caption": "B. Expression of endothelial Notch target genes in microvascular endothelial cells isolated from skeletal muscle of mice fasted for 24 hours (Fasted group) and then refed for 4 hours (Fasted+Refed group) normalized to mice fed for 24 hours (Fed group). n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Notch: 18131///18128///18132///18129"
  },
  {
    "caption": "C. Blood glucose levels of control (n=5) and NICDiOE-EC (n=5) mice five weeks after recombination. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "D. Plasma insulin levels of control (n=5) and NICDiOE-EC (n=5) mice five weeks after recombination. Data represent mean ± SEM, Welch's t-test.",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "E. Blood glucose levels for insulin tolerance test of control (n=7) and NICDiOE-EC control (n=7) mice. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "G. Blood glucose levels for glucose tolerance test of control (n=6) or NICDiOE-EC (n=7) mice. Data represent mean ± SEM, unpaired t-test. H. Quantification of area under the curve for glucose tolerance test in G. Data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "A. Blood glucose levels of control (n=8) and Rbpji∆EC (n=8) mice five weeks after recombination. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "B. Plasma insulin levels of control (n=8) and Rbpji∆EC (n=8) mice five weeks after recombination. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "C. Blood glucose levels for insulin tolerance test of control (n=10) and Rbpji∆EC (n=7) mice. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "E. Blood glucose levels for glucose tolerance test of control (n=6) or RbpjiΔEC (n=5) mice. Data represent mean ± SEM, unpaired t-test. F. Quantification of area under the curve for glucose tolerance test in E. Data represent mean ± SEM, Welch's t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "A. Uptake of FITC-insulin and CAV1 expression in primary human umbilical venous ECs (HUVECs) upon Notch induction. Scale bar 20 µm.",
    "ncbi_link": "Notch: 4854///4855///4853///4851"
  },
  {
    "caption": "C. Representative western blot of AKT phosphorylation in gastrocnemius muscle 7 minutes after intravenous injection of PBS or 1.5 U/kg insulin in control (n=3) and Rbpji∆EC (n=3) mice five weeks after recombination. D. Densitometric analysis of western blot in C. n=3, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "E. Representative western blot of AKT phosphorylation in liver 7 minutes after intravenous injection of PBS or 1.5 U/kg insulin in control (n=3) and Rbpji∆EC (n=3) mice five weeks after recombination. F. Densitometric analysis of western blot in E. n=3, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "C. Representative western blot of AKT phosphorylation in C2C12 cells upon Cav1 knockdown in mouse cardiac endothelial cells (MCECs). D. Densitometric analysis of western blot in C. Data represented as fold change over control. n=3, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Cav1: 12389"
  },
  {
    "caption": "A. Quantitative RT-PCR detection of CAV1, CAV2 and CAVIN1 in primary human umbilical venous endothelial cells (HUVECs) upon Notch blockade (dnMAML) and induction (NICD). n=3, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "NICD: 
CAV1: 857
CAV2: 858
CAVIN1: 284119
MAML: 9794"
  },
  {
    "caption": "D. Representative western blot of CAVIN1 expression in HUVECs upon Notch induction. E. Densitometric analysis of western blot in D. Data represented as fold change over LacZ control. n=5, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Notch: "
  },
  {
    "caption": "F. Expression of CAV1 in HUVECs upon Notch manipulation and HEY1 induction. n=3, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "CAV1: 857
HEY1: 23462"
  },
  {
    "caption": "G. Expression of Cav1, Cav2, Cavin1 in primary microvascular ECs freshly isolated from skeletal muscle of RbpjiΔEC mice compared to control mice. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Cav1: 12389
Cav2: 12390
Cavin1: 19285
Rbpj: 19664"
  },
  {
    "caption": "H. Expression of Cav1, Cav2, Cavin1 in primary microvascular ECs freshly isolated from skeletal muscle of NICDiOE-EC mice compared to control mice. n=4, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Cav1: 12389
Cav2: 12390
Cavin1: 19285
NICD: 18128"
  },
  {
    "caption": "I. Expression of Cav1, Cav2, Cavin1 in microvascular endothelial cells isolated from skeletal muscle of mice kept on control diet (CD, 10% fat, 70% carbohydrates) or high-fat diet (HFD, 60% fat, 20% carbohydrates) or high-fat and sugar diet (HFS, 60% fat, 20% carbohydrates and 42 g/l sucrose in drinking water). n=4, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Cav1: 12389
Cav2: 12390
Cavin1: 19285"
  },
  {
    "caption": "J, K. Quantification of number of caveolae attached to apical membrane in EC of cardiac capillaries from NICDiOE-EC mice (6 segments of 1000 nm length from 3 hearts per genotype) or RbpjiΔEC (6 segments of 1000 nm length from 8 hearts per genotype) based on electron microscopy. Box plot depicts median and percentiles (10th, 25th, 75th, 90th), unpaired t-test, * means p<0.05.",
    "ncbi_link": "NICD: 18128
Rbpj: 19664"
  },
  {
    "caption": "Representative immune-histochemistry of Cav1 staining in heart sections from control and RbpjiΔEC mice. n=3, scale bar 50 µm.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "Representative confocal images of Cav1 staining in heart sections from control and RbpjiΔEC mice. n=3, scale bar 50 µm.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "B. Blood glucose levels of control and NICDiOE-EC mice during the 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "C. Plasma insulin levels of control and NICDiOE-EC mice during the 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "D. 2-DG uptake levels in skeletal muscle of control and NICDiOE-EC mice. n=5, data represent mean ± SEM, unpaired t-test. E. 2-DG uptake levels in visceral white adipose tissue (vWAT) of control (n=4) and NICDiOE-EC (n=5) mice. Data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "NICD: 18128"
  },
  {
    "caption": "G. Blood glucose levels of control and RbpjiΔEC mice during the 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "H. Plasma insulin levels of control and RbpjiΔEC mice during the 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "I. 2-DG uptake levels in skeletal muscle of control and RbpjiΔEC mice. n=4, data represent mean ± SEM, unpaired t-test. J. 2-DG uptake levels in vWAT of control and RbpjiΔEC mice. n=5, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "B. Blood glucose levels for glucose tolerance test (GTT) of control (n=4) or RbpjiΔEC (n=5) mice kept on high-fat diet (HFD). Data represent unpaired t-test, mean ± SEM. C. Quantification of area under curve (AUC) for GTT in B. Data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "D. Blood glucose levels for insulin tolerance test (ITT) of control (n=4) or RbpjiΔEC (n=3) mice kept on HFD. Data represent unpaired t-test, mean ± SEM. E. Quantification of AUC for ITT in D. Data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "F. HbA1c levels of control (n=4) or RbpjiΔEC (n=6) mice kept on HFD seven weeks after recombination. Data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "H. Blood glucose levels of control and RbpjiΔEC mice on HFD during 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "I. Plasma insulin levels of control and RbpjiΔEC mice on HFD during 2-DG uptake assay. n=5, data represent mean ± SEM, unpaired t-test.",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "J. 2-DG uptake levels in skeletal muscle of control (n=5) and RbpjiΔEC (n=4) mice on HFD. Data represent mean ± SEM, unpaired t-test. K. 2-DG uptake levels in vWAT of control and RbpjiΔEC mice. n=4, data represent mean ± SEM, unpaired t-test. ",
    "ncbi_link": "Rbpj: 19664"
  },
  {
    "caption": "Primary rat cortical neurons transfected with eGFP-GA50 were examined to determine at which time points preceding cell death aggregates are found in neurites. Two days post-transfection, aggregates formed by eGFP-GA50 (green) are detectable in neurites (SMI-32 staining in red). These aggregates remain localized to neurites at 96 hours (4 days) and 288 hours (8 days). Colocalization is indicated by yellow overlay of colors (right panels). Inset below each image shows enlargement of neurite regions containing aggregates, Representative fields from 60x magnification z-stack confocal images, scale bar indicates 20μm. Inset scale bars indicate 5μm.",
    "ncbi_link": "eGFP: 
GA50: "
  },
  {
    "caption": "Primary rat neurons were co-transfected with Td-tomato and eGFP-GAn plasmids or eGFP-alone. The same neurons were imaged at 24-hour intervals to assess viability. A) Representative fields (right) of eGFP and eGFP-GA50 cortical neurons at days 1, 7, and 13 post-transfection follow the survival of individual cells over time (white arrows). 20x magnification, scale bar indicates 25μm. ",
    "ncbi_link": "eGFP: 
GA: 
Td-tomato: "
  },
  {
    "caption": "Primary cortical or motor neurons were co-transfected with mCherry or mCherry-GA50 and GCaMP6f. After 48 hours, mCherry positive cells were determined. Green fluorescence intensity was then recorded from identified neurons. Basal fluorescence was monitored prior to induced depolarization via perfusion with ACSF containing 50mM KCl. A) Representative images of a co-transfected cortical neuron expressing mCherry-GA50 (left panel) and GCaMP6f (right two panels). This image shows a representative demonstration of the increase in detectable green fluorescence from the GCaMP6f indicator pre- and post- stimulation (center and right respectively). 40x magnification, scale bar indicates 25μm.",
    "ncbi_link": "GA50: 
GCaMP6f: 
mCherry: "
  },
  {
    "caption": "eGFP-GAn dipeptides were expressed in primary cortical or motor neurons for 48 hours, then immunostained for neurofilament (gray) and SV2 (red). A-B) Representative z-stack confocal images of neurites from eGFP, eGFP-GA50, and eGFP-GA100 expressing cortical (A) or motor (B) neurons. 60x magnification, scale bar indicates 5μm. ",
    "ncbi_link": "eGFP: 
GA50: 
GA100: "
  },
  {
    "caption": "C-D) Quantification of SV2 puncta along neurites in cortical neurons (C) or motor neurons (D) by ImageJ manual counting, normalized to eGFP-only expressing cells. (C) Cortical neurons demonstrated a significant GA-length dependent reduction, as well as a reduction in all cells containing GA-repeats greater than 50 (left panel). (D) Motor neurons demonstrated a significant GA-length dependent reduction, as well as a reduction in all cells containing GA-repeats greater than 100 (left panel). Evaluation of neurite length by NeuronJ software revealed no differences in total neurite length per cell in cortical neurons (C) or motor neurons (D) expressing any GA-repeat length compared with eGFP alone (right panels).",
    "ncbi_link": "GA: "
  },
  {
    "caption": "i3 cortical neurons from a C9orf72-ALS patient and the paired isogenic control were differentiated for 21 days, then were immunostained for neurofilament (red), and SV2 (green) (A) Shown are representative z-stack confocal images of neurites.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "B) i3 cortical neurons from a C9orf72-ALS patient and the paired isogenic control were differentiated for 21 days, then were immunostained for synaptophysin (green) (B). Shown are representative z-stack confocal images of neurites.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "Quantification of SV2 (C) colocalized with neurofilament normalized to neurofilament area. This analysis revealed a significant reduction in SV2 levels in the C9orf72 line compared with the isogenic control, Data presented as mean ± SEM. Unpaired t-test, *p < 0.05. 15 non-overlapping regions from 3 differentiated wells for each genotype were evaluated.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "Quantification of Synaptophysin (D) colocalized with neurofilament normalized to neurofilament area. This analysis revealed a significant reduction in SV2 levels in the C9orf72 line compared with the isogenic control, while synaptophysin remained unaltered. Data presented as mean ± SEM. Unpaired t-test, *p < 0.05. 15 non-overlapping regions from 3 differentiated wells for each genotype were evaluated.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "E) mRNA was Trizol extracted from 3 independent wells of C9-ALS and isogenic i3 cortical neurons. RNA was converted to cDNA using the Superscript First-strand kit, and q-PCR was performed using PowerUp SYBR Green. Measurements were normalized to the housekeeping gene GAPDH and then to isogenic levels. Analysis was performed using the ΔΔCT method. 2ΔΔCT ± SE, is presented. Unpaired t-test, **p < 0.01.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "F) Whole cell lysates were generated from 3 independent wells of C9-ALS and isogenic i3 cortical neurons differentiated for 21 days. Lysates were immunoblotted for SV2, and normalized to total protein loading. Quantification band intensities revealed a significant decrease in SV2 protein levels in the C9orf72 lines compared with the isogenic. Data presented as mean ± SEM. Unpaired t-test, *p < 0.05.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "Whole cell lysates were generated from iMNs differentiated for 32 days. Lysates were immunoblotted for SV2 (G) Loading controls were β-actin Quantification band intensities normalized to loading controls revealed a trend towards reduction in SV2 protein levels in the C9orf72 cell lines compared with controls Data presented as mean ± SEM. Unpaired t-test. Samples from 5 independent control and 4 independent C9orf72 patient lines were used.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "Whole cell lysates were generated from iMNs differentiated for 32 days. Lysates were immunoblotted for synaptophysin (H). Loading controls were total protein loading. synaptophysin levels remained unaltered. Data presented as mean ± SEM. Unpaired t-test. Samples from 5 independent control and 4 independent C9orf72 patient lines were used.",
    "ncbi_link": "C9orf72: "
  },
  {
    "caption": "A) Cortical neurons were loaded with FM4-64 dye 48 hours after transfection with eGFP-GA50 and transduction with rSV2a-eGFP-pRRL lentivirus. Basal fluorescence was monitored prior to induced depolarization via perfusion with ACSF containing 50mM KCl. Graphical representation is the change in fluorescence (ΔF) normalized to basal fluorescence (F), ΔF/F. The final 60 seconds of baseline recording and 60 seconds of the depolarization phase are shown, arrow indicates start of depolarization. The lack of synaptic release in the case of GA50 expression (red line) was rescued back to levels comparable to eGFP controls (pink line) in the case of coexpression of rSV2a-eGFP-pRRL (orange line). Statistical significance was determined using the Sidak-Bonferroni method, ***p < 0.001, n=10 puncta regions from each of 4 biological replicates.",
    "ncbi_link": "eGFP: 
GA50: 
SV2: 22987///9899///9900"
  },
  {
    "caption": "B) Cortical neurons were co-transfected with mCherry or mCherry-GA50 and GCaMP6f, then transduced with rSV2a-eGFP-pRRL. Green fluorescence intensity was recorded from identified mCherry positive neurons. Basal fluorescence was monitored prior to induced depolarization via perfusion with ACSF containing 50mM KCl. Quantification of the peak change in fluorescence (ΔF) following ACSF perfusion normalized to basal fluorescence (F), ΔF/F. The significant increase in Ca2+ influx observed following GA50 expression (*p < 0.05) is resolved when rSV2a-eGFP-pRRL is coexpressed. Data presented as mean ± SEM. One-way ANOVA with Sidak's multiple comparisons test, at least 10 cells per condition, pooled from n= 3 independent biological experiments. No significant differences were observed between mCherry or mCherry+SV2 conditions, groups were merged for this analysis.",
    "ncbi_link": "eGFP: 
GA50: 
GCaMP6f: 
mCherry: 
SV2: 117559
SV2a: 117559"
  },
  {
    "caption": "Neurons were co-transfected with mCherry-GAn plasmids or mCherry-alone and transduced with rSV2a-eGFP-pRRL, then imaged at 24-hour intervals. (C) Kaplan-Meier survival analysis of cortical neurons expressing GA50 or GA50+SV2 followed for 13 days. The significant cellular toxicity induced by GA50 is rescued by SV2 replenishment. While the hazard ratio of GA50 was 1.473, this was decreased to 0.7227 for GA50+SV2. At least 190 cells per condition were evaluated from a pooling of n=3 independent experiments, log-rank Mantel-Cox test, ****p < 0.0001. No significant differences were observed between eGFP or eGFP+SV2 conditions, and groups were merged for this analysis as Control. (D) A Kaplan-Meier survival analysis was performed for PR50 and PR50+SV2 containing cells. Under these conditions significant toxicity is observed regardless of increased SV2 levels, with the hazard ratio of PR50 containing cells (1.772) remaining high for those expressing PR50+SV2 (1.784). At least 150 cells per condition were evaluated from a pooling of n=3 independent experiments, log-rank Mantel-Cox test, ****p < 0.0001. No significant differences were observed between eGFP or eGFP+SV2 conditions, and groups were merged for this analysis as Control.",
    "ncbi_link": "eGFP: 
GA: 
GA50: 
mCherry: 
PR50: 
SV2: 117559
SV2a: 117559"
  },
  {
    "caption": "(E) Kaplan-Meier survival analysis of motor neurons expressing GA50 or GA50+SV2 followed for 10 days. The significant cellular toxicity induced by GA50 is rescued by SV2 replenishment. While the hazard ratio of GA50 was 1.345, this was decreased to 0.7769 for GA50+SV2. At least 200 cells per condition were evaluated from a pooling of n=3 independent experiments, log-rank Mantel-Cox test, ****p < 0.0001.",
    "ncbi_link": "GA50: 
SV2: 117559"
  },
  {
    "caption": "Spinal cord lysates were generated from fresh frozen tissue of 20-month old mice either expressing GA149-CFP under the Thy1 promoter (Tgx GA149) or wild type controls. Lysates were immunoblotted for SV2 (A) Total protein levels were determined by imaging the Mini-PROTEAN TGX stain-free gel prior to transfer. Quantification of band intensities normalized to total protein loading revealed a significant reduction in SV2 protein levels in the GA-expressing cohort compared with wild type animals, Data presented as mean ± SEM. Unpaired t-test, *p< 0.05. A total of 4 animals per group were examined.",
    "ncbi_link": "CFP: 
GA: 
GA149: 
Thy1: 21838"
  },
  {
    "caption": "Spinal cord lysates were generated from fresh frozen tissue of 20-month old mice either expressing GA149-CFP under the Thy1 promoter (Tgx GA149) or wild type controls. Lysates were immunoblotted for synaptophysin (B) Total protein levels were determined by imaging the Mini-PROTEAN TGX stain-free gel prior to transfer. synaptophysin levels remained unaltered. Data presented as mean ± SEM. Unpaired t-test, *p< 0.05. A total of 4 animals per group were examined.",
    "ncbi_link": "CFP: 
GA149: 
Thy1: 21838"
  },
  {
    "caption": "Spinal cord lysates were generated from fresh frozen tissue of 20-month old mice either expressing GA149-CFP under the Thy1 promoter (Tgx GA149) or wild type controls. Lysates were immunoblotted for PSD-95 (C). Total protein levels were determined by imaging the Mini-PROTEAN TGX stain-free gel prior to transfer. PSD-95 levels remained unaltered. Data presented as mean ± SEM. Unpaired t-test, *p< 0.05. A total of 4 animals per group were examined.",
    "ncbi_link": "CFP: 
GA149: 
Thy1: 21838"
  },
  {
    "caption": "Muscle sections (30μm) were cut from snap frozen tissue of 20-month old GA149 mice (Tgx GA149) or wild type controls. Immunohistochemical staining was performed to assess synaptic protein levels in proximity to NMJs. Sections were immunostained for SV2 or Synaptophysin, and counterstained with neurofilament. A) Left Panels: Representative images show SV2 levels (green) in proximity to α-bungarotoxin positive NMJs (red) in wild type animals (top) versus GA149 animals (bottom). Right Panels: Representative images show SV2 levels (green) overlapping with neurofilament (blue) at synaptic terminals approaching muscle in wild type animals (top) versus GA149 animals (bottom). ",
    "ncbi_link": "GA149: "
  },
  {
    "caption": "B-C) Quantification of SV2 (B) or Synaptophysin (C) colocalized with neurofilament and normalized to neurofilament area. This analysis revealed a significant reduction in SV2 levels in GA149 animals compared with wild types, while synaptophysin remained unaltered. Data presented as mean ± SEM. Unpaired t-test, *p< 0.05. A total of 10 non-overlapping regions of muscle from each of 5 animals per group were evaluated.",
    "ncbi_link": "GA149: "
  },
  {
    "caption": "Colocalization of AcGFP-Siwi, AcGFP-BmAgo3 and mCherry-BmVasa in BmN4 cells. Line scans (white line in the enlarged region) show that Siwi-D670A mutant but not BmAgo3-D697A mutant dissociates from BmVasa foci. Line scans of fluorescence intensity were normalized to the highest value and depicted at the right panel. Scale bar, 8 μm.",
    "ncbi_link": "mCherry: 
BmAgo3: 100125337
Siwi: 100125336"
  },
  {
    "caption": "Colocalization of AcGFP-Siwi and mCherry-BmDcp2 in BmN4 cells. Line scans (white line in the enlarged region) show that Siwi-D670A mutant but not BmAgo3-D697A mutant overlaps with BmDcp2 foci. Line scans of fluorescence intensity were normalized to the highest value and depicted at the right panel. Scale bar, 8 μm.",
    "ncbi_link": "BmAgo3: 100125337
Siwi: 100125336"
  },
  {
    "caption": "Depletion of BmSpnE or BmQin results in segregation of Siwi-D670A from BmDcp2-containing P-bodies. (Top-left) Representative Z-projections (Maximum intensity). Scale bar 8 μm. (Top-right) Enlarged area from the white box. Scale bar 2 μm. (Bottom) Box plot showing that depletion of BmQin (n=32 cells) or BmSpnE (n=32 cells) reduces colocalization ratio between Siwi-D670A and BmDcp2, compared to control (dsRLuc, n=32 cells). Representative data from N = 3 independent experiments are shown. Bonferroni-corrected P-values were calculated by Asymptotic Wilcoxon rank sum test. See also Figure EV3.",
    "ncbi_link": "BmQin: 
RLuc: 
BmSpnE: 101743633"
  },
  {
    "caption": "Depletion of Siwi results in segregation of BmQin from BmDcp2-containing P-bodies. Box plot showing that depletion of Siwi (dsSiwi, n=47 cells) reduces colocalization ratio between BmQin and BmDcp2, compared to control (dsRLuc, n=55 cells). Representative data from N = 4 independent experiments are shown. Depletion of Siwi results in segregation of BmSpnE from BmDcp2-containing P-bodies. Box plot showing that depletion of Siwi (dsSiwi, n=55 cells) reduces colocalization ratio between BmSpnE and BmDcp2, compared to control (dsRLuc, n=55 cells). Representative data from N = 6 independent experiments are shown. Depletion of Siwi results in colocalization of BmSpnE and BmVasa. Box plot showing that depletion of Siwi (dsSiwi, n=18 cells) significantly up-regulates colocalization ratio between BmSpnE and BmVasa, compared to control (dsRLuc, n=18 cells). Representative data from N = 3 independent experiments are shown. Depletion of BmVasa results in segregation of Siwi from BmAgo3 foci. Box plot showing that depletion of BmVasa (dsBmVasa, n=12 cells) down-regulates colocalization ratio between Siwi and BmAgo3, compared to control (dsRLuc, n=12 cells). Data points collected from N = 2 independent experiments are shown (statistical test is not performed for N < 3 data). Depletion of BmVasa results in entanglement of Siwi at piP-bodies. Interaction interfaces are indicated by white arrows. Box plot showing that depletion of BmVasa (dsBmVasa, n=45 cells) mildly up-regulates colocalization ratio between Siwi and BmDcp2, compared to control (dsRLuc, n=49 cells). Representative data from N = 5 independent experiments are shown.",
    "ncbi_link": "RLuc: 
Siwi: 100125336
BmVasa: 692765"
  },
  {
    "caption": "Split violin plots of piRNA expression fold change between AcGFP (control) and piRNA factor(s) overexpressed libraries. Overexpression of Siwi-D670A, BmVasa-E339Q and both mutants increase non-TE-derived piRNA (red, 626 genes) while TE-derived piRNA (blue, 818 genes) does not change. Bonferroni-corrected P-values and the effect sizes (r) were calculated by Asymptotic Wilcoxon rank sum test.",
    "ncbi_link": "GFP: 
Siwi: 100125336
BmVasa: 692765"
  },
  {
    "caption": "The expression of SAMHD1 is negatively correlated with EV71 viral replication ability. HEK293T and RD cells were infected with EV71 at a MOI of 0.1, then the cells and supernatants were harvested at the indicated time points. Immunoblotting (IB) analysis of EV71 VP1 in cells, with tubulin as a loading control. EV71-VP1 protein in the supernatants was detected after ultracentrifugation.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "The expression of SAMHD1 is negatively correlated with EV71 viral replication ability. HEK293T and RD cells were infected with EV71 at a MOI of 0.1, then the cells and supernatants were harvested at the indicated time points. EV71 viral RNA levels in cell lysates and supernatants were detected by RT-qPCR with GAPDH as a control. (n=3, mean±SD, ns stands for no significance, paired t-test)",
    "ncbi_link": "GAPDH: 
SAMHD1: 25939"
  },
  {
    "caption": "The expression of SAMHD1 is negatively correlated with EV71 viral replication ability. HEK293T and RD cells were infected with EV71 at a MOI of 0.1, then the cells and supernatants were harvested at the indicated time points. The mRNA levels of the host restriction factors were detected by RT-qPCR in infected or uninfected HEK293T or RD cells, and the expression levels of the target genes were normalized to GAPDH. (n=3, mean±SD, ns stands for no significance, paired t-test).",
    "ncbi_link": "GAPDH: 
SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. The stable cell lines pLKO.1 and sh-SAMHD1 constructed in HEK293T cells were infected with EV71 at a MOI of 0.1 and 0.05 respectively, and cells and supernatants were harvested at the indicated time points. IB analysis of EV71 VP1 and SAMHD1 in cells was performed with tubulin as a loading control. EV71-VP1 protein in the supernatants was detected after ultracentrifugation.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. EV71 viral RNA in cell lysates was detected by RT-qPCR with GAPDH as a control (n=3, mean±SD, * P < 0.05, ** P < 0.01, paired t-test).",
    "ncbi_link": "GAPDH: 
SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. Viral titers in the supernatants were measured by the cytopathic effect method.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. The stable cell lines pLKO.1 and sh-SAMHD1 constructed in RD (H) cells were infected with EV71 at a MOI of 0.1 and 0.05 respectively, and cells and supernatants were harvested at the indicated time points. IB analysis of EV71 VP1 and SAMHD1 in cells was performed with tubulin as a loading control. EV71-VP1 protein in the supernatants was detected after ultracentrifugation.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. EV71 viral RNA in cell lysates was detected by RT-qPCR with GAPDH as a control (n=3, mean±SD, * P < 0.05, ** P < 0.01, paired t-test).",
    "ncbi_link": "GAPDH: 
SAMHD1: 25939"
  },
  {
    "caption": "SAMHD1 knockdown enhances EV71 replication. Viral titers in the supernatants were measured by the cytopathic effect method.",
    "ncbi_link": "SAMHD1: 25939"
  },
  {
    "caption": "HEK293T cells transfected with VR1012, which is a eukaryotic expression vector, or Vpx-HA were infected with EV71 at a MOI of 0.1, and then cells and supernatants were harvested at the indicated time points. IB analysis of EV71-VP1, SAMHD1 and Vpx-HA in cell lysates was performed with tubulin as a loading control. EV71-VP1 was detected in the supernatants after ultracentrifugation.",
    "ncbi_link": "HA: 
Vpx: 1490006"
  },
  {
    "caption": "EV71 viral RNA was detected in cell lysates by RT-qPCR with GAPDH as a control (n=3, mean±SD, ** P <0.01, paired t-test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Stable SAMHD1-HA-overexpressing cell lines were constructed in HEK293T and RD cells and detected by IB with pLVX as a negative control.",
    "ncbi_link": "HA: 
SAMHD1: 25939"
  },
  {
    "caption": "RD SAMHD1-HA cell lines were treated with dimethyl sulfoxide (DMSO) or 10 μM MG132 for 12 h prior to harvest and subjected to IB with tubulin as a loading control.",
    "ncbi_link": "HA: 
SAMHD1: 25939"
  },
  {
    "caption": "RD SAMHD1-HA cell lines were treated as in (B), and then HA immunoprecipitation (IP) and IB were performed. The IP elution was analyzed by mass spectrometry.",
    "ncbi_link": "HA: 
SAMHD1: 25939"
  },
  {
    "caption": "TRIM21 induced the degradation of SAMHD1, and MG132 rescued the TRIM21-mediated degradation of SAMHD1. HEK293T cells were cotransfected with SAMHD1 and VR1012 or TRIM21 expression plasmids with or without MG132 treatment for 12 h prior to harvest, and then subjected to IB with tubulin as a loading control.",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "TRIM25 (E) induced the degradation of SAMHD1 HEK293T cells were cotransfected with SAMHD1 and VR1012 or TRIM25 expression plasmids and then subjected to IB with tubulin as a loading control.",
    "ncbi_link": "SAMHD1: 25939
TRIM25: 7706"
  },
  {
    "caption": "Reverse co-IP confirmed the interaction between SAMHD1 and TRIM21. SAMHD1-flag was transfected with TRIM21-HA into HEK293T cells, and then the cells were treated as in (B) and subjected to HA IP and IB.",
    "ncbi_link": "flag: 
HA: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "mRNA levels of TRIM21 in RD and HEK293T cells.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "TRIM21 Knockout in RD cells released SAMHD1 inhibition on EV71 replication. Negative control or RD-CRISPR-Cas9-TRIM21 RD cells were infected with EV71 at a MOI of 0.05 for the indicated time and harvested for SAMHD1, TRIM21 and EV71-VP1 detection by IB. Tubulin served as a loading control.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "TRIM21 Knockout in RD cells released SAMHD1 inhibition on EV71 replication. EV71 RNA levels in (B) were detected by RT-qPCR with GAPDH as a control (n=3, mean±SD, ** P < 0.01, paired t-test).",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "TRIM21 Knockout in RD cells released SAMHD1 inhibition on EV71 replication. Viral titres in the supernatant were measured by the cytopathic effect method. The results represent the means ± SD from three independent experiments. Statistical significance was analyzed using Student's t test (**P < 0.01).",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "Overexpression of TRIM21 in HEK293T cells increased EV71 replication by degrading SAMHD1. HEK293T cells were transfected with VR1012 or TRIM21-HA for 24 h and then infected with EV71 at a MOI of 0.05. Cells were harvested at the indicated time points and subjected to IB with tubulin as a loading control.",
    "ncbi_link": "HA: 
TRIM21: 6737"
  },
  {
    "caption": "Overexpression of TRIM21 in HEK293T cells increased EV71 replication by degrading SAMHD1. HEK293T cells were transfected with VR1012 or TRIM21-HA for 24 h and then infected with EV71 at a MOI of 0.05. EV71 viral RNA in cell lysates was detected by RT-qPCR with GAPDH as a control (n=3, mean±SD, ** P < 0.01, paired t-test)).",
    "ncbi_link": "GAPDH: 
HA: 
TRIM21: 6737"
  },
  {
    "caption": "TRIM21 itself has no effect on EV71 replication. VR1012 or TRIM21 was transfected into pLKO.1 or sh-SAMHD1 HEK293T cells for 24 h and infected with EV71. Cells were harvested and subjected to IB analysis.",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "TRIM21 itself has no effect on EV71 replication. VR1012 or TRIM21 was transfected into pLKO.1 or sh-SAMHD1 HEK293T cells for 24 h and infected with EV71. Viral titers in the supernatants were measured by the cytopathic effect method. The results represent the means ± SD from three independent experiments. Statistical significance was analyzed using Student's t test (*P < 0.05).",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "The mRNA levels of SAMHD1 and TRIM21 in different tissues of neonatal mice were detected by RT-qPCR with GAPDH as a control, and the expression of SAMHD1 and TRIM21 in the heart was set as 100% (n=3, mean±SD, * P < 0.05, paired t-test).",
    "ncbi_link": "GAPDH: 
SAMHD1: 56045
TRIM21: 20821"
  },
  {
    "caption": "The mRNA levels of EV71 virus and host factors in mock or EV71 infected mice were detected by RT-qPCR with GAPDH as a control. The expression of EV71 (D) were presented, and the levels of corresponding gene in mock infected mice were set as 100%",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "The mRNA levels of EV71 virus and host factors in mock or EV71 infected mice were detected by RT-qPCR with GAPDH as a control. The expression of , IFNα and IFNβ (E) were presented, and the levels of corresponding gene in mock infected mice were set as 100%",
    "ncbi_link": "GAPDH: 
IFNα: 111654
IFNβ: 15977"
  },
  {
    "caption": "The mRNA levels of EV71 virus and host factors in mock or EV71 infected mice were detected by RT-qPCR with GAPDH as a control. The expression of SAMHD1 and TRIM21 (F) were presented, and the levels of corresponding gene in mock infected mice were set as 100%",
    "ncbi_link": "GAPDH: 
SAMHD1: 56045
TRIM21: 20821"
  },
  {
    "caption": "IB analysis of THP-1 cells treated with scrambled shRNA, TRIM21-specific shRNA or SAMHD1-specific shRNA. Tubulin served as loading control. Quantification of SAMHD1 and TRIM21 levels in whole cells in which the indicated genes were knocked down by shRNA. Data are normalized to tubulin and expressed as the fold change over cells treated with pLKO.1 without HIV infection (n=3, mean±SD).",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "sh-SAMHD1 and sh-TRIM21 THP-1 cells were treated with PMA for 24 h and infected with the VSV-G pseudotyped reporter HIV-1, then detected 48 h later by flow cytometry analysis (n=3, mean±SD, * P < 0.05, ** P < 0.01, *** P < 0.001, paired t-test).",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737
VSV-G: 1489834"
  },
  {
    "caption": "Quantification of SAMHD1 and TRIM21 levels in whole cells in which the indicated genes were knocked down by shRNA. Data are normalized to tubulin and expressed as the fold change over cells treated with pLKO.1 without HIV infection (n=3, mean±SD). IB analysis of MDM cells from 3 donors transfected with TRIM21 siRNA twice at days 1 and 3, respectively, after MDM differentiation.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "MDM cells treated with TRIM21 siRNA were infected with VSV-G-pseudotyped HIV-1 reporter and then detected 48 h later by flow cytometry analysis (n=3, mean±SD, ** P < 0.01, paired t-test).",
    "ncbi_link": "TRIM21: 6737
VSV-G: 1489834"
  },
  {
    "caption": "Quantification of SAMHD1 and TRIM21 levels in whole cells in which the indicated genes were knocked down by shRNA. Data are normalized to tubulin and expressed as the fold change over cells treated with pLKO.1 without HIV infection (n=3, mean±SD). IB analysis of Jurkat and KG-1 cells treated with scrambled shRNA or TRIM21-specific shRNA.",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "Jurkat and KG-1 cells treated with TRIM21 shRNA were infected with HIV-1, then detected 48 h later by flow cytometry analysis (n=3, mean±SD, ns stands for no significance, paired t-test).",
    "ncbi_link": "TRIM21: 6737"
  },
  {
    "caption": "TRIM21 interacts with SAMHD1 via PRY and SPRY domains. The effect of TRIM21 on the degradation of SAMHD1. SAMHD1-flag was cotransfected with VR1012, TRIM21 WT or the indicated mutant into HEK293T cells for 48 h, and the cells were subjected to IB with tubulin as loading control.",
    "ncbi_link": "flag: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "TRIM21 interacts with SAMHD1 via PRY and SPRY domains. SAMHD1-flag was cotransfected with VR1012 or TRIM21 WT or the indicated mutant for 24 h, and the cells were then treated with 10 μM MG132 for 12 h before harvest and subjected to HA IP and IB.",
    "ncbi_link": "flag: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "The effect of TRIM21 on SAMHD1 WT or its mutants. SAMHD1-HA or the indicated mutant were cotransfected with VR1012 or TRIM21-flag into HEK293T cells for 48 h, and the cells were subjected to IB with tubulin as a loading control.",
    "ncbi_link": "flag: 
HA: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "SAMHD1-flag 1-547 was cotransfected with VR1012 or TRIM21-HA for 24 h, and the cells were then treated with 10 μM MG132 for 12 h before harvest and subjected to HA IP and IB.",
    "ncbi_link": "flag: 
HA: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "SAMHD1 109-626 followed with a His tag or TRIM21-PRYSPRY followed with a GST tag were expressed in Rosetta (DE3), and pull-down assay were performed with Ni-Sepharose (up) and GST Sepharose (down), respectively.",
    "ncbi_link": "GST: 
His: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "The effect of TRIM21 on SAMHD1 proteins from various species. HEK293T cells were transfected with VR1012 or TRIM21 and the indicated SAMHD1 expression vector, then subjected to IB analysis. Tubulin served as a loading control.",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "The effect of TRIM21 on hSAMHD1 mutants. HEK293T cells were transfected with VR1012 or TRIM21 and SAMHD1 mutants for 48 h and then subjected to IB analysis. Tubulin served as a loading control.",
    "ncbi_link": "SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "SAMHD1-flag WT or the G153S or G183R mutant was cotransfected with VR1012 or TRIM21-HA for 24 h, and the cells were then treated with 10 μM MG132 for 12 h before harvest and subjected to HA IP and IB. Tubulin served as a loading control.",
    "ncbi_link": "flag: 
HA: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "SAMHD1-HA WT or the indicated mutants were cotransfected with VR1012 or TRIM21-flag into HEK293T cells for 48 h, and the cells were subjected to IB with tubulin as a loading control.",
    "ncbi_link": "flag: 
HA: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "SAMHD1-HA WT and VR1012 or TRIM21 were cotransfected with K48-only and K63-only ubiquitin-flag into HEK293T cells for 24 h, and the cells were then treated with 10 μM MG132 for 12 h before harvest and subjected to HA IP and IB with tubulin as a loading control.",
    "ncbi_link": "flag: 
HA: 
ubiquitin: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "K48-only ubiquitin-flag and SAMHD1-HA WT or mutant K622R were cotransfected with VR1012 or TRIM21 into HEK293T cells as indicated. The cells were then treated with 10 μM MG132 for 12 h before harvest and subjected to HA IP and IB with tubulin as a loading control.",
    "ncbi_link": "flag: 
HA: 
ubiquitin: 
SAMHD1: 25939
TRIM21: 6737"
  },
  {
    "caption": "VR1012, SAMHD1-HA WT or the K622R mutant was transfected into HEK293T-shSAMHD1 cells for 24 h. The cells were then infected with EV71 at a MOI of 0.1 and harvested at the indicated time points. SAMHD1-HA, TRIM21 and EV71-VP1 were detected by IB with tubulin as a loading control.",
    "ncbi_link": "HA: 
SAMHD1: 25939"
  },
  {
    "caption": "(Top) PCR detection of the recombined BrafLox−V600E allele (Lox-V600E) in BVE mouse tissues at 8 weeks of age without tamoxifen induction. Substantial recombination is observed in the lung, while weaker recombination is also detected in the liver. No recombination was detected in hematopoietic tissues (bone marrow and spleen) even after 40 cycles of amplification (right). (Bottom) H&E staining of lung sections from wild-type (WT, 10 weeks of age), BVE (1-10 weeks of age) and Braf+/LSL−V600E mouse 8 weeks after nasal delivery of AdCre is indicated below. V600EBRAF expression induced by two different methods causes similar pathology showing papillary adenomas accompanied by stroma development. Scale bars, 100 μm.",
    "ncbi_link": "Cre: 
Braf: 109880
BRAF: 109880"
  },
  {
    "caption": "PCR detection of Braf recombination in purified IMCs, AT2 cells and tumour cell aggregates.",
    "ncbi_link": "Braf: 109880"
  },
  {
    "caption": "Co-culture of AT2 cells and autologous IMCs from BVE mice (8- to 10-week-old) for 48 h using the Transwell® culture system. In vitro BrdU incorporation (flow cytometry, left and middle) and EMT marker expression (RT-PCR, right) in co-cultured AT2 cells are indicated. Representative flow cytometry plots are indicated on the left, and the bar chart in the middle indicates % BrdU+ AT2 cell numbers normalised to control cultures without IMCs (n = 4, mean + SD). Gapdh serves as a loading control for the RT-PCR on the right.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "CT imaging of lungs of AdCre-infected Braf+/LSL−V600E mice treated with vehicle (top) or CCR1 inhibitor (bottom). H: heart; * indicates a tumour region accompanied by atelectasis.",
    "ncbi_link": "Cre: 
Braf: 109880"
  },
  {
    "caption": "H&E staining of lung sections from vehicle (left) or CCR1 inhibitor (right) treated AdCre-infected Braf+/LSL−V600E mice. Scale bars, 250 μm (top) or 50 μm (bottom).",
    "ncbi_link": "Cre: 
Braf: 109880"
  },
  {
    "caption": "Flow cytometry analysis of CD11c+ (top, green) and SPC+ (bottom, red) cells in the lung of AdCre-infected Braf+/LSL−V600Emice treated with vehicle (left) or CCR1 inhibitor (right).LungCD11c+ (left) and SPC+ (right) cell numbers (per left lobe) were quantitated in AdCre-infected Braf+/LSL−V600Emice treated with CCR1 inhibitor or vehicle (V) (n = 3, mean + SD).% LungCD4+ (left) and CD8+ (right) T lymphocytes were quantitated in AdCre-infected Braf+/LSL−V600E mice treated with CCR1 inhibitor or vehicle (V) (n = 3, mean + SD).",
    "ncbi_link": "Cre: 
Braf: 109880"
  },
  {
    "caption": "NPC2 immunoblots of concentrated whole lung CM (top) and whole lung lysates (bottom) generated from Braf+/+;CreER™ (WT) or BVE (VE) mice. Whole lung lysates were obtained from 3-to 8-week-old mice.",
    "ncbi_link": "Cre: 
Braf: 109880
ER: 13983///13982"
  },
  {
    "caption": "Npc2 mRNA expression in the purified IMC and AT2 populations as determined by quantitative RT-PCR. Mean + SD (n = 3) of Npc2 expression normalised to Gapdh is indicated.",
    "ncbi_link": "Gapdh: 
Npc2: 67963"
  },
  {
    "caption": "Npc2 mRNA expression in IMCs cultured for 48 h with or without 50 μg/ml bNPC2 as determined by qRT-PCR. Mean ± SD (n = 3) of Npc2 expression normalised to Hprt1 is indicated.",
    "ncbi_link": "Hprt1: 
Npc2: 67963"
  },
  {
    "caption": "Shortened survival of BVE mice following reduction in Npc2 gene dosage. Genotypes of mice are as follows: +/+ = Braf+/LSL−V600E;CreER+/0;Npc2+/+, +/hypo = Braf+/LSL−V600E;CreER+/0,Npc2+/hypo, hypo/hypo = Braf+/LSL−V600E;CreER+/0;Npc2hypo/hypo. Median survival time (MST) for each genotype is indicated.",
    "ncbi_link": "Cre: 
Braf: 109880
ER: 13983///13982
Npc2: 67963"
  },
  {
    "caption": "Representative H&E staining of lung sections from 5-week-old BVE mice on the Npc2+/+ (+/+) or Npc2+/hypo (+/hypo) background is shown. Scale bars, 500 μm.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Stroma IMC quantification per lung in Npc2+/+ (+/+) or Npc2+/hypo (+/hypo) BVE mice at different ages (39-109 days p.p.).",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Ki67/Mac2immunofluorescence analysis of Npc2+/+ (+/+) and Npc2+/hypo (+/hypo) BVElung sections at 5 weeks of age. Merged images for Ki67 (green), Mac2 (red) and DAPI (blue) are indicated. Arrows indicate dual positive cells for nuclearKi67 and Mac2. Scale bars, 50 μm. The bar chart indicates % Ki67 in Mac2+lung stroma cells (mean + SD), obtained from 4 independent Npc2+/+ and Npc2+/hypoBVE pairs.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "In vivo BrdU incorporation of CD11c+ IMCs from Npc2+/+ (+/+) and Npc2+/hypo (+/hypo) BVE mice are shown. Representative flow cytometry plots of three independent experiments are indicated.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Ki67 (green)/Mac2 (red) dual immunofluorescencestaining of lung sections from 5-week-old Npc2+/hypoBVEmice with nuclearDAPI (blue) staining, focusing on intratumour Mac2+cell clusters. Scale bar, 50 μm. Enlarged images of the boxed areas 1 and 2 highlight Ki67+Mac2− cells associated with Mac2+ cells (arrows).",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Lung SPC+/CD11c+cell numbers of Braf+/LSL−V600E;Npc2+/+ (+/+, n = 3) and Braf+/LSL−V600E;Npc2+/hypo (+/hypo, n = 7) mice at 10 weeks post-AdCre infection.",
    "ncbi_link": "Cre: 
Braf: 109880
Npc2: 67963"
  },
  {
    "caption": "Intracellular un-esterified cholesterol distribution as detected by filipin staining in freshly isolated Npc2+/+ and Npc2+/hypo IMCs. Scale bars, 25 μm. Filipin-stained cells were graded from 0 to 3+ as indicated in the microphotographs (see Materials and Methods for criteria), and % of each grade in IMCs from Npc2+/+ (+/+) and Npc2+/hypo (+/hypo) BVE mice is shown in the bar chart. The data were obtained by analysing 176 Npc2+/+ and 242 Npc2+/hypo IMCs from three independent Npc2+/+ and Npc2+/hypo pairs.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "CLSM imaging of fresh Npc2+/hypo IMCs stained with filipin (cyan) and LAMP2 immunofluorescence (purple). Scale bars, 5 μm. Coarse structures strongly stained with filipin are surrounded by cytoplasmic membranous staining of LAMP2. Single-colour greyscale images are also demonstrated in the middle (filipin) and right (LAMP2).",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Intracellular un-esterified cholesterol distribution as detected by filipin staining in Npc2+/hypo IMCs cultured with or without 50 μg/ml bNPC2 for 48 h. Scale bars, 25 μm. Quantitative data in the bar graph were obtained by analysing 265 bNPC2-untreated (-bNPC2) and 252 bNPC2-treated (+bNPC2) cells from three independent cultures using the method described in (A).",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Immunoblot and qRT-PCR analyses of CCL6 expression in Npc2+/+ IMCs cultured with or without 50 μg/ml bNPC2 for 48 h. The data in the bar graph (qRT-PCR) represent mean + SD; n = 3.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "CLSM imaging of CCL6 (green)/LAMP1 (red) immunofluorescence of Npc2+/+ IMCs cultured with or without 50 μg/ml bNPC2 for 48 h. Scale bars, 10 μm. The right bottom image highlights the boxed area of the merged image of bNPC2-treated IMCs showing partial co-localisation of LAMP1 and CCL6.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "Immunoblot analysis of intracellular and secreted (CM) CCL6 in bafilomycin-treated Npc2+/+ IMC culture. IMCs without (left) or with (right) 50 μg/ml bNPC2 pre-loading for 30 min were chased in serum-free DMEM for 3 h and then treated with 200 nM bafilomycin A1 for 24 h.",
    "ncbi_link": "Npc2: 67963"
  },
  {
    "caption": "A.-E. Staining for β-galactosidase in 3-months old VEGF-Ahyper(lacZ/wt)mouseeyes.A. Low magnification image shows β-gal+ cells (in blue) in the RPE (white arrow), retina (blue arrow), ciliary body (black arrow), and lens (orange arrow). Images of Figures 1B to 1E are higher magnification images of Figure 1A. Scale bar 200 μm.B. Strong expression of VEGF with β-gal+ cells are observed in the RPE (short white arrow) and the inner nuclear layer (INL) (long white arrow), while less staining is observed in the ganglion cell layer (black arrow) of the retina. Scale bar 100 μm.C. Ciliary body epithelial cells are β-gal+, similarly as RPE cells (white arrow). Scale bar 100 μm.D. VEGF-A is strongly expressed in secondary nuclearfiber cells in the adult lens (white arrow). Scale bar 50 μm.E. No β-gal+ cells are observed in the corneas of adult VEGF-Ahyper(lacZ/wt)mouseeyes. White arrow shows the stroma of the cornea and the black arrow shows the corneal epithelium. Scale bar 100 μm.",
    "ncbi_link": "lacZ: 
VEGF-A: 22339"
  },
  {
    "caption": "G. RPE cells maintain strong expression of VEGF-A (β-gal+ cells [white arrow]) in the retina with progressive age. Immunofluorescence for β-gal in the retina of a 24-months old VEGF-Ahypermouse is shown. Ocular macrophages (F4/80+ cells [yellow arrow]) show no strong β-galactosidase expression, while some immunolabeling for β-galactosidase is detected in retinal cells of the inner nuclear layer (orange arrow) of the retina. RPE: retinal pigment epithelium; ONL: outer nuclear layer; INL: inner nuclear layer. Scale bar 50 μm.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "H. VEGF-A continues to be highly expressed in secondary nuclear fiber cells in the aged lens (shown is a lens of a 24-months old VEGF-Ahyper mouse; nuclear β-galactosidasestaining (arrow) reflects cellular VEGF-A expression). Cor: lenscortex; Cap: lens capsule. DAPI labels nuclei (blue). Scale bar 25 μm.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "A. Left graph: VEGF-Aprotein levels in lenses of VEGF-Ahypermice (KI) are increased ~3-fold throughout life (measured at 2- and at 8.5-months of age; n=7 mice/group, 2 independent experiments). Graph shows mean ± SD. Right graph: VEGF-AmRNA levels are similarly increased in lenses of adult VEGF-Ahypermice (9-months old; n=7 mice/group, 3 independent experiments). Graph shows mean ± SEM. **P-value: 0.0095.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "B. VEGF-A isoforms (mainly VEGF-A120 and VEGF-A164) and the VEGF-A receptor Flk1 are expressed in the adult lens. Flt1 expression was not detected in the lens. N=3 mice/group.",
    "ncbi_link": "Flt1: 14254
Flk1: 16542
VEGF-A: 22339"
  },
  {
    "caption": "C. Increased serum levels of the lipid peroxidation marker 4-HNE (a marker of increased oxidative damage) in aged, but not in young VEGF-Ahyper mice. *P-value: 0.0325. N=7 mice/group (2 independent experiments). Graph shows mean ± SEM.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "A. Increased ERK1/2 phosphorylation is observed in lenses from VEGF-Ahyper mice (KI) with increased VEGF-A levels already prior to cataract formation (11-months old mice with no cataracts (0 cataract)), which is maintained in lenses with mature cataracts (lens of a 26-months old VEGF-Ahyper mouse with +3 cataract). Quantification of ERK1/2 phosphorylation in 11-months old lenses (n=3/group). Graph shows mean ± SEM. ***P-value: 0.0005.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "B.-C. Cataracts with opacification of the lens (B., black arrow) and extruded nuclei (C., white arrow) are observed with progressive age in VEGF-Ahyper mice (here a representative 30-months old lens with a cataract is shown).",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "F.-G. Representative histological images of 21-months old eyes from WT and VEGF-Ahyper mice. The sclerotic nucleus (red arrow in G.) was extruded and the lenscortex and capsule are separated from the nucleus (white arrow in G.). The retina in aged VEGF-Ahyper mice is atrophic and shows degenerative changes (yellow arrow in G.), while the retina (*) and lens (**) appears normal in age-matched WT littermate mice. Scale bars 200 μm. DAPI (blue, nuclei); phalloidin (green).",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "A. lens progress with age in VEGF-Ahypermice. lens were graded from +1 (mild), +2 (moderate), to +3 (mature cataract with fully opacified lens). While only a small subset of >18 months-old WT mice have mature (+3) cataracts, the majority of VEGF-Ahypermice of this age group has mature cataracts. Percentile (%) of mice with graded cataracts is indicated in each age group. 0 = no cataract. Absolute mouse numbers of each group are shown in Appendix Figure S1.B. Targeting NLRP3 inhibits normal age-dependent cataract formation, and delays (but does not prevent) VEGF-A-induced cataract formation in VEGF-Ahypermice. Percentile (%) of mice with graded cataracts is indicated in each age group. 0 = no cataract. Absolute mouse numbers of each group are shown in Appendix Figure S1.",
    "ncbi_link": "NLRP3: 216799
VEGF-A: 22339"
  },
  {
    "caption": "C. Expression of IL-1β in lenses of 21-months old VEGF-Ahyper mice with +3 cataracts is increased compared to lenses from age-matched WT mice with +3 cataracts, but not in lenses from 11-months old mouse groups with no cataracts. *P-value: 0.0259. N=7/group (3 independent experiments).",
    "ncbi_link": "IL-1β: 16176
VEGF-A: 22339"
  },
  {
    "caption": "D. VEGF-Ahyper mice have decreased levels of the major antioxidant in the lens, reduced glutathione (μmol/gm lens weight), prior to cataract formation. Lenses with 0 to +1 cataracts from 11-months old mice were used for measurements. ** P-value: 0.0097. N=7/group (2 independent experiments).",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "E-F. Overexpression of NADPH oxidase gp91phox [*p-value: 0.0435] (E.) and of the antioxidant enzymes SOD1 [*p-value: 0.0330], catalase (CAT) [*p-value: 0.0448] and GPx-1 [*p-value: 0.0443] (F.) in 21-months old lenses of VEGF-Ahyper mice with cataracts (+3), but not in 11-months old lenses with no cataracts. N=7/group (3 independent experiments).",
    "ncbi_link": "gp91phox: 13058
VEGF-A: 22339"
  },
  {
    "caption": "E-F. Overexpression of NADPH oxidase gp91phox [*p-value: 0.0435] (E.) and of the antioxidant enzymes SOD1 [*p-value: 0.0330], catalase (CAT) [*p-value: 0.0448] and GPx-1 [*p-value: 0.0443] (F.) in 21-months old lenses of VEGF-Ahyper mice with cataracts (+3), but not in 11-months old lenses with no cataracts. N=7/group (3 independent experiments).",
    "ncbi_link": "catalase: 12359
GPx-1: 14775
SOD1: 20655
VEGF-A: 22339"
  },
  {
    "caption": "A-B. Choroidalflat mount staining of a white VEGF-Ahypermouse shows choroidalvessels (green [fluorescein-conjugated isolectin B4]) from which neovessels (strong red [CD31]) originate and that are covered by a RPEcell layer (white [phalloidin]), which separates the CNV lesion from the photoreceptors. White arrows demarcate CNV lesion. Yellow arrows show round autofluorescent deposits. Scale bars 100 μm.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "A-B. Choroidalflat mount staining of a white VEGF-A hypermouse shows choroidal vessels (green [fluorescein-conjugated isolectin B4]) from which neovessels (strong red [CD31]) originate and that are covered by a RPEcell layer (white [phalloidin]), which separates the CNV lesion from the photoreceptors. White arrows demarcate CNV lesion. Yellow arrows show round autofluorescent deposits. Scale bars 100 μm.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "C. Section through a CNV lesion in a VEGF-Ahyper mouse. Bruch's membrane location is indictaed by yellow arrows. Choroidal neovessels (white arrows) are covered by a layer of RPE cells (black arrows). Chor: choroid; ONL: outer nuclear layer; PR: photoreceptors. Scale bar 20 μm. A.-C. 21-months old VEGF-Ahyper mice.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "RPE-specific overexpression of VEGF-A in VMD2Cre+/WTROSA-STOPfl/fl-VEGF-A164mice (VEGF-ARPEmice) results in CNV at sites of VEGF-A overexpression (Cre+ patches (white nuclei); red arrow), while Cre- areas with normal VEGF-A expression show no CNV (white arrow). Neovessels are CD31+ (red). VEGF-A-induced CNV lesions and RPE barrier breakdown in VMD2Cre+/WT ROSA-STOPfl/fl-VEGF-A164mice resemble those seen in VEGF-Ahypermice (B.-C., arrows; phalloidin staining in green). Scale bars 100 μm.",
    "ncbi_link": "Cre: 
ROSA-STOP: 
VMD2: 24115
VEGF-A: 22339"
  },
  {
    "caption": "D. Genetic inactivation of Flk1 specifically in the RPE in VEGF-Ahypermice (VMD2Cre+/WTFlk1fl/flVEGF-Ahypermice) prevents RPE barrier breakdown and CNV lesion formation. Choroidalflat mounts of 5 months old VEGF-Ahypermice and VMD2Cre+/WTFlk1fl/flVEGF-Ahypermice are shown. β-galstaining shows uniform VEGF-A expression in these mice (green). Crestaining (red) shows co-localization of β-gal and Crestaining in the nuclei of RPE cells in VMD2Cre+/WTFlk1fl/flVEGF-Ahypermice (red areas of staining occur in CNV lesions of VEGF-Ahypermice due to labeling of anti-mouseIgG and not Cre, as the anti-mouseIgG secondary antibodies were used to detect the mouse anti-Cre antibody). Phalloidinstaining (white) reveals extensive RPE barrier breakdown and CNV lesions (arrow) in VEGF-Ahypermice, which is not observed in VMD2Cre+/WTFlk1fl/flVEGF-Ahypermice. Scale bar 100 μm.",
    "ncbi_link": "Cre: 
VMD2: 24115
Flk1: 16542
VEGF-A: 22339"
  },
  {
    "caption": "A. NLRP3 is expressed in RPE cells at sites of CNV lesions (arrow; white).B. Lack of NLRP3 staining in VEGF-Ahyper/NLRP3-/- mice (control). Scale bars 100 μm.",
    "ncbi_link": "NLRP3: 216799
VEGF-A: 22339"
  },
  {
    "caption": "C. Expression of NLRP3 [*p-value: 0.0478] and IL-1β [*p-value: 0.0398], but not of IL-18 [p-value: 0.3529] is increased in RPE/choroid lysates from VEGF-Ahyper mice when compared to matched control littermate mice. N=7 mice/group (3 independent experiments). Graphs show mean ± SEM.",
    "ncbi_link": "IL-18: 16173
IL-1β: 16176
NLRP3: 216799
VEGF-A: 22339"
  },
  {
    "caption": "D.-G. Complement pathway activation (immunolabeling for the product of complement pathway activation C5b-9, an inducer of the NLRP3 inflammasome) is observed in CNV lesions of VEGF-Ahypermice (white arrow in E.) but not in age-matched control mice (D.) Co-localization of C5b-9 in the same CNV lesion is observed with complement C1qA (the initiator of the classical complement pathway and an inducer of the NLRP3 inflammasome) (F.), and with TLR2 (G.) (white arrows). Autofluorescence in red in D. and E. CD31+vessels in red in I. and J. Yellow arrows show site of choroid. Scale bars 50 μm.",
    "ncbi_link": "VEGF-A: 22339"
  },
  {
    "caption": "A. CNV lesion numbers per eye in 6-week old VEGF-Ahypermice compared with VEGF-Ahypermice lacking CASP1/CASP11, NLRP3, IL1R1, IL-18, TLR2, or those heterozygous for beclin-1 or homozygous for hypomorphic ATG16L1. CASP1/CASP11, NLRP3 or IL-1R1 deficiency results in significantly fewer CNV lesions. Each value represents the total CNV lesion number/eye for an individual mouse. Mean ± SEM is shown. P-values are based on comparison with the VEGF-Ahypermouse group. Absolute numbers of mice per group are indicated in ( ). P-values were calculated with a two-tailed unpaired Student's t-test. Separately, p-values are shown between VEGF-Ahyper/CASP1-/-/CASP11-/- and VEGF-Ahyper/NLRP3-/- or VEGF-Ahyper/IL1R1-/-mouse groups. WT mice developed no CNV lesions.",
    "ncbi_link": "ATG16L1: 77040
beclin-1: 56208
CASP1: 12362
CASP11: 12363
IL-18: 16173
IL-1R1: 16177
IL1R1: 16177
NLRP3: 216799
TLR2: 24088
VEGF-A: 22339"
  },
  {
    "caption": "B. Average CNV lesion area (in μm2/lesion) in 6-week old VEGF-Ahypermice compared with VEGF-Ahypermice lacking CASP1/CASP11, NLRP3, IL1R1, IL-18, TLR2, or those heterozygous for beclin-1 or homozygous for hypomorphic ATG16L1. Lack of TLR2 or CASP1/CASP11 significantly reduces CNV lesion size, while reduced autophagy moderately increases CNV size. Each value represents the average CNV lesion size/eye for an individual mouse. Mean ± SEM is shown. P-values are based on comparison with the VEGF-Ahypermouse group. Absolute numbers of mice per group are indicated in ( ). P-values were calculated with a two-tailed unpaired Student's t-test. Separately, p-values are shown between VEGF-Ahyper/CASP1-/-/CASP11-/- and VEGF-Ahyper/NLRP3-/- or VEGF-Ahyper/IL1R1-/-mouse groups.",
    "ncbi_link": "ATG16L1: 77040
beclin-1: 56208
CASP1: 12362
CASP11: 12363
IL-18: 16173
IL1R1: 16177
NLRP3: 216799
TLR2: 24088
VEGF-A: 22339"
  },
  {
    "caption": "C.-E. Representative choroidal flat mount images show multifocal CNV lesions in VEGF-Ahyper mice and a significant reduction in CNV numbers in those VEGF-Ahyper mice that lack either CASP1/CASP11 or IL1R1 (and therefore IL-1β-signaling). Staining for phalloidin in green and for CD31 in red. Scale bars 200 μm.",
    "ncbi_link": "CASP1: 12362
CASP11: 12363
IL-1β: 16176
IL1R1: 16177
VEGF-A: 22339"
  },
  {
    "caption": "Figure 9: VEGF-A-induced non-exudative AMD-like pathologies can be prevented by targeting NLRP3, IL1R1 or caspase-1/caspase-11.A. No significant abnormalities of the choroid, RPE or retina are seen in control wild-type littermate mice. Representative image of a 28-months old control eye is shown. White arrow indicates normal Bruch's membrane. Chor: choroid; RPE; PR: photoreceptor; ONL: outer nuclear layer.B. Aged VEGF-Ahypermice develop a progressive age-dependent degeneration of the RPE (red arrow) and the photoreceptors (yellow arrow) with accumulation of thick sub-RPE basal laminar deposits (black arrow). These non-exudative AMD-like pathologies occur also at sites devoid of CNV lesions.C.-E. Genetic inactivation of CASP1/CASP11, NLRP3, or IL1R1 strongly inhibits the manifestation of RPE and photoreceptor degeneration in aged VEGF-Ahypermice.F.-G. VEGF-Ahyper/IL18-/-mice show significant RPE and photoreceptor degeneration, with shortened and irregular photoreceptor outer segments (white arrows). Thick sub-RPE deposits that protrude into the RPE plane are observed as well (black arrows).H. VEGF-Ahyper/Becn1+/-mice show significant RPE and photoreceptor degeneration.I. In contrast, age-matched VEGF-Ahypomice that are hypomorphic for VEGF-A and express β-galactosidase from the endogenous VEGF-A locus (as do VEGF-Ahypermice) do not show these eye pathologies.B-I. 21-months old mice. Scale bars 20 μm.",
    "ncbi_link": "Becn1: 56208
CASP1: 12362
CASP11: 12363
IL18: 16173
IL1R1: 16177
NLRP3: 216799
VEGF-A: 22339"
  },
  {
    "caption": "A. Graphs show means of a- and b-waves of dark-adapted and light-adapted ERG responses (ERG intensities in μV) for both the left and the right eyes from 21-months old VEGF-Ahypermice, VEGF-Ahyper/CASP1-/-/CASP11-/-mice, CASP1-/-/CASP11-/-mice, VEGF-Ahyper/IL1R1-/-mice, IL1R1-/-mice, VEGF-Ahyper/IL18-/-mice, and IL18-/-mice. None of these mice had cataracts. Graphs show mean ± SEM.",
    "ncbi_link": "CASP1: 12362
CASP11: 12363
CASP11: 12363///12363
IL18: 16173
IL1R1: 16177
VEGF-A: 22339"
  },
  {
    "caption": "B. Representative ERG tracings are shown for VEGF-Ahyper mice and for VEGF-Ahyper/CASP1-/-/CASP11-/- mice. X-axes show milliseconds (ms). Y-axes show ERG intensities (in μV).",
    "ncbi_link": "CASP1: 12362
CASP11: 12363
VEGF-A: 22339"
  },
  {
    "caption": "Figure 11: Lack of caspase-1/caspase-11 inhibits CNV lesion formation, retinal degeneration, fundus abnormalities and fundus autofluorescence in aged VEGF-Ahyper mice.A. OCTs in aged VEGF-Ahypermice show retinal degeneration with a thinning of the retina and CNV lesions extending from the choroid into the subretinal space (arrows). OCTs appear normal in age-matched VEGF-Ahyper/CASP1-/-/CASP11-/-mice and CASP1-/-/CASP11-/-mice.B. Fundus autofluorescence imaging shows areas of autofluorescence in the fundus of aged VEGF-Ahypermice, but not in age-matched VEGF-Ahyper/CASP1-/-/CASP11-/-mice and CASP1-/-/CASP11-/-mice.C. Abnormal pigment loss and degenerative changes are observed in the fundus of aged VEGF-Ahypermice, while the fundus of age-matched VEGF-Ahyper/CASP1-/-/CASP11-/-mice and CASP1-/-/CASP11-/-mice does not show these abnormalities.Representative images of 21-months old mice are shown.",
    "ncbi_link": "CASP1: 12362
CASP11: 12363
VEGF-A: 22339"
  },
  {
    "caption": "Coronal and axial brain MRI of the patient with compound heterozygote mutations in ECE2 shows nodules of heterotopic neurons lining the lateral ventricles.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "ECE2 expression on RNA level. In situ hybridisation for ECE2 RNA in 50d old cerebral organoids (COs) shows higher signal in the cortical plate-like zone (CP') (Scalebar=100 µm). Ventricle-like lumen in COs is marked as V'.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "COs transfected with micro-RNAs targeting ECE2 (KD) or scrambled negative control (CTRL) and GFP and analysed 7 days later reveal an increase in ectopic neurons upon ECE2 KD (Transfected cells are shown in green, NEUN+ neuronal nuclei in magenta. d=day. Scalebar=25 µm). Ventricle-like lumen in COs is marked as V'.",
    "ncbi_link": "GFP: 
ECE2: 9718"
  },
  {
    "caption": "Graph depicting the number of ectopically located NEUN+ cells in CTRL and KD electroporated COs using two different micro-RNAs targeting ECE2. Data shown as box plot (mean = red line, median = black line, box represents 25th and 75th percentiles, whiskers extend to 10th and 90th percentiles, all outliers are shown; n=number of ventricles analysed; ***P < 0.001 in Kruskal-Wallis One Way ANOVA on Ranks and Dunn's Pairwise Multiple Comparison).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Quantification of distribution of GFP+ transfected cells 1dpe upon CTRL and Ece2 KD by IUE (n=3 CTRL and 4 Ece2 KD brains; *P=0.044 in One-way ANOVA and Tukey's Multiple Pairwise Comparison; data shown as mean±SEM).",
    "ncbi_link": "Ece2: 9718"
  },
  {
    "caption": "High magnification images of GFP and Pax6 showing that ectopic progenitors are mostly not transfected. D-J, E13-16 Ece2 KD.",
    "ncbi_link": "Ece2: 107522"
  },
  {
    "caption": "GFP-Pax6+ progenitors delaminate upon Ece2 KD (red arrows), leaving behind a region free of Pax6+ cells in the VZ (yellow circle) and forming ectopic rosettes (yellow box).",
    "ncbi_link": "Ece2: 107522"
  },
  {
    "caption": "Reduction in apical Arl13b in the electroporation site (white arrowheads) indicates loss of apical belt integrity and disruption of apico-basal polarity upon Ece2 KD.",
    "ncbi_link": "Ece2: 107522"
  },
  {
    "caption": "Reduction in β-catenin in the electroporation site (white arrowheads) indicates loss of apical belt integrity and disruption of apico-basal polarity upon Ece2 KD.",
    "ncbi_link": "Ece2: 107522"
  },
  {
    "caption": "Brightfield images of 60d old CTRL and ECE2 KO COs show normal formation of neuroepithelial structures.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "ISH for ECE2 confirms the absence of ECE2 mRNA in 60d old ECE2 KO COs (pink dotted line indicates position of the CP').",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": ", FACS analysis of 60d old ECE2 KO COs reveals an increase in progenitors and decrease in neurons (n=7-8 samples of 3 pooled organoids each from 3 different batches; **P < 0.01; ***P < 0.001 in One Way ANOVA and Tukey Pairwise Multiple Comparison).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Example images of IHC for PH3+ cells in 60d old CTRL and ECE2 KO COs. Quantification of PH3+ cycling cells in 60d old COs, normalised to length of the apical surface of ventricle-like structures, shows an increase upon ECE2 KO (Data shown as box plots with median as black line, mean as red line; n=number of analysed ventricles from 2 batches of COs; One Way ANOVA: **P = 0.004).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "In ECE2 KO COs, more ventricles are disorganised in terms of neuronal localisation as revealed from MAP2+ cell bodies in the progenitor zone (n=number of ventricles from 2 independent batches; two-tailed Mann Whitney U (U = 458) and chi-square test: χ2(2)=25.42, ****P < 0.0001).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Quantification of actin levels from Westernblot of whole CO lysate reveals a reduction in ECE2 KO COs (n=4 independent batches of CTRL and ECE2 KO COs with 3 pooled COs each sample; *P = 0.021 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Fractionation of G- and F-actin from CTRL and ECE2 KO COs and analysis via Westernblot additionally reveals an increase in G- at the expense F-actin upon ECE2 KO, suggesting a reduction in F-actin belt integrity (n=4 independent batches of CTRL and ECE2 KO COs with 3 pooled COs each; *P = 0.021 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "The thickness of the apical F-actin belt is increased in ECE2 KO COs. C, Example images of apical F-actin belt in 60d old CTRL and ECE2 KO COs with F-actin labeled by AlexaFluor594-conjugated Phalloidin (Scalebar=100 µm). D, Quantification of the thickness of apical F-actin belt in Fiji [86] by measuring the area of F-actin and dividing by the length of apical surface reveals significant increase in ECE2 KO COs (Box plots: mean=red line, median=black line, box represents 25th and 75th percentiles, whiskers extend to 10th and 90th percentiles, all outliers are shown; n=number of analysed ventricles in 2 batches; Kruskal-Wallis One Way ANOVA on Ranks and Dunn's Pariwise Multiple Comparison: ***P < 0.001).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "IHC for ARL13B and F-ACTIN in 60d old CTRL and ECE2 KO COs shows disruption of honeycomb-like structure of the apical adherens belt and of apico-basal polarity in terms of apically localised primary cilium in ECE2 KO COs (Scalebar = 10µm).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "The microtubule cytoskeleton is changed in COs upon ECE2 KO. Example images of ac-tub IHC in CTRL vs. ECE2 KO COs (Scalebar = 100 µm).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "The microtubule cytoskeleton is changed in COs upon ECE2 KO. Quantification of ac-tub in ventricles of ECE2 KO COs by measurement of the mean grey value in Fiji shows significant reduction upon ECE2 KO (n=number of analysed ventricles; *P = 0.019 in One Way ANOVA and Tukey Pairwise Multiple Comparison).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Apico-basal polarity is impaired upon ECE2 inhibition and KO as visible in example images of ARL13B IHC in CTRL vs. KO COs (H; Scalebar = 100 µm). Quantification of germinal zones for normally high ("1") vs. reduced ("0") apical ARL13B reveals a reduction in the proportion of normal ventricles in the absence of ECE2 (n=number of analysed ventricles from 2 batches; ****P < 0.0001 in exact binomial test).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Analysis of CTRL and ECE2 KO COs 1 dpe with GAP43-GFP reveals RG that delaminated (white arrowheads) and/or lost their bipolar morphology (red arrowheads) in the KO COs (Scalebar = 25 µm).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Binning analysis 1 dpe after forced exression of ECE2 in the developing mouse cortex reveals ectopic positioning of Pax6+GFP+ neural progenitors with significantly reduced localisation to bin2 (A) and increased localisation of Ctip2+ deep layer neurons to bin2 with reduction in bin5 (B) (for binning strategy see Figure EV2B; n=3 CTRL and 5 ECE2 OX brains E13-14; data shown as bars with mean±SEM; *P < 0.05 and **P < 0.01 in Student's t-test).",
    "ncbi_link": "ECE2: 107522"
  },
  {
    "caption": "Example images E13-14 of IHC for Pax6 and Ctip2 upon CTRL and ECE2 OX conditions (Scalebar = 100 µm; electroporated cells shown in green). Ventricle marked by V.",
    "ncbi_link": "ECE2: 107522"
  },
  {
    "caption": "E13-16 images and analysis of ECE2 OX in the developing mouse cortex reveal ectopic positioning of Sox2+ (D) progenitors and Ctip2+ deep- (D) and Satb2+ upper layer neurons (E) (Scalebars = 100 µm; electroporated cells shown in green). F, Quantification at 3dpe, counting the proportion of brains with normal vs. abnormal positioning of Sox2+ neural progenitors and Ctip2+ and Satb2+ neurons and that of brains with intact vs. disrupted basal membrane (n=5 CTRL and 8 ECE2 OX brains; exact binomial test: ****P < 0.0001). Ventricle marked by V.",
    "ncbi_link": "ECE2: 107522"
  },
  {
    "caption": "ECE2 OX in COs (electroporated cells shown in green; Scalebars = 50 µm; n = number of CO ventricles analysed from 2 batches). G, Example images of COs 7 days after CTRL or ECE2 OX electroporation and IHC for PH3+ mitotic cells and NEUN+ neuronal nuclei. H, Quantification of PH3+ cells relative to electroporated apical surface length reveals a reduction upon ECE2 OX in CTRL CO background (*P = 0.046 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison). I, Quantification of GFP+ neurons as proportion of all GFP+ cells reveals an increase upon ECE2 OX in COs (*P = 0.021 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison). J, Quantification of ectopic neurons localising to the VZ' relative to electroporated radial units (GFP+ cells in the VZ') reveals a significant increase upon ECE2 OX (***P < 0.001 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison). Ventricle-like lumen marked by V'.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": ", Forced expression of ECE2 in ECE2 KO COs rescues neuronal positioning. K, Example images of CTRL and ECE2 electroporated ECE2 KO COs 7 dpe. L, Quantification of ectopic neurons relative to electroporated radial units reveals a decrease upon ECE2 OX in ECE2 KO COs, thus rescueing the neuronal positioning phenotype in the absence of ECE2 OX (**P = 0.002 in Kruskal-Wallis One Way Analysis of Variance on Ranks and Dunn's Pairwise Comparison). Ventricle-like lumen marked by V'.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Volcano plot visualizes the proteomic analysis from 60d old CO lysates showing proteins with significantly lower and higher expression upon ECE2 KO (n=3 batches of 60d old CTRL and ECE2 KO COs; FDR 0.05; s0 1; dashed lines indicating the cut-off; names of example proteins are shown).",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "Volcano plot of proteomic analysis of cell culture supernatant from 55d old CTRL and ECE2 KO COs shows two significantly downregulated proteins (red) in the secretome (n=3 batches of CTRL and ECE2 KO COs; FDR 0.05; s0 1; dashed lines indicating the cut-off). Non-significantly changed proteins of interest are highlighted in green below the cut-off curves.",
    "ncbi_link": "ECE2: 9718"
  },
  {
    "caption": "(C) Cell lines of human and animal origin were inoculated with pseudotyped VSV harboring VSV-G, SARS-S or 2019-nCoV-S. At 16 h postinoculation, pseudotype entry was analyzed. Shown are the combined data of three experiments. Error bars indicate SEM.",
    "ncbi_link": "2019-nCoV-S: 43740568
SARS-S: 1489668
VSV-G: 1489834"
  },
  {
    "caption": "(C) 293T cells transiently expressing ACE2 of human (dark blue) or bat (light blue) origin, human APN (purple) or hDPP4 (green) were inoculated with pseudotyped VSV harboring VSV-G, SARS-S, 2019-nCoV-S, MERS-S or 229E-S. At 16 h postinoculation, pseudotype entry was analyzed. The average of three independent experiments is shown. Error bars indicate SEM.",
    "ncbi_link": "ACE2: 59272
APN: 290
hDPP4: 1803
2019-nCoV-S: 43740568
229E-S: 918758
MERS-S: 14254594
SARS-S: 1489668
VSV-G: 1489834"
  },
  {
    "caption": "(C) 293T cells transiently expressing ACE2 alone or in combination with TMPRSS2 were incubated with CatB/L inhibitor E64d or PBS as control and inoculated with pseudotypes bearing the indicated viral surface proteins. The average of three independent experiments is shown in panels A-C. Error bars indicate SEM. Statistical significance was tested by two-way ANOVA with Dunnett posttest.",
    "ncbi_link": "ACE2: 59272
TMPRSS2: 7113"
  },
  {
    "caption": "entry.Pseudotypes harboring the indicated viral surface proteins were incubated with different dilutions of serum from a convalescent SARS patient and subsequently inoculated onto 293T cells that transiently express ACE2 in order to evaluate cross-neutralization. The results from a representative experiment with triplicate samples are shown and were confirmed in a separate experiment. Error bars indicate SD. Statistical significance was tested by two-way ANOVA with Dunnett posttest.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(a) Haematoxylin and eosin (H & E) staining of kidneys from control (Flcnflox/flox), Flcn KO, Flcn/Tfeb DKO, Flcn/Tfe3 DKO, Flcn/Tfe3 DKO; Tfeb-HET and Flcn KO; Tfeb-HET mice at p18 (replicated three times). Scale bars, 3 mm (upper panels). Boxed areas are magnified in the bottom panels. Arrowhead indicates tubular papillary atypical hyperplasia. Scale bars, 100 μm (lower panels).",
    "ncbi_link": "Flcn: 216805
Tfe3: 209446
Tfeb: 21425"
  },
  {
    "caption": "Plots show tumor volumes in mice injected with UOK257/shLuc (n=8) or UOK257/shTFEB (n=10) (b) p value = 0.036 for plot in (b)",
    "ncbi_link": "Luc: 
TFEB: 7942"
  },
  {
    "caption": "Kaplan-Meier analysis of mice survival relative to the two experimental groups. Long-rank test, p < 0.0001. The median survival time of mice injected with UOK257/shLuc is 219.5 days in (c)",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Plots show tumor volumes in mice injected with UOK257/shLuc (n=8) or UOK257/shTFE3 (n=9) (e) *p= 0.023 for plot in (e)",
    "ncbi_link": "Luc: 
TFE3: 7030"
  },
  {
    "caption": "Kaplan-Meier analysis of mice survival relative to the two experimental groups. The median survival time of mice injected with UOK257/shLuc is 244.5 days in (f).",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Proteins co-purifying with Mta1, Mta2 or Mta3 in IP-mass spectrometry experiments in wild type cells (top) or Mbd3-null cells (bottom). Proteins showing significant enrichment with the bait protein are located outside the dotted lines. For all panels the protein being immunoprecipitated is indicated in red, the other MTA proteins in purple, and other NuRD components in blue. Each IP/Mass spec experiment set comprised three independent immunoprecipitations from one nuclear extract preparation.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Relative enrichment of indicated proteins in MTA pulldowns from wild type (WT) or Mbd3-null (Mbd3KO) ES cells, normalised to 2x MTA proteins. NuRD components comprising the remodelling subunit are labelled in blue, those comprising the deacetylase subunit in red. As MTA proteins are the bait in these experiments, they may be isolated more efficiently than their interaction partners. Error bars represent standard deviation from three (Mta1 and Mta2) or six (Mta3) replicate pulldowns.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Western blot of a time course of Mta3 deletion in Mta1∆Mta2∆Mta3Flox/Flox: Cre-ER (Mta12∆3F/F) or Control (Mta12∆3F/F without Cre-ER) ES cells probed for indicated NuRD component proteins or RNA Polymerase II as a loading control (αRNAPII). The time course is indicated at the top as Days + tamoxifen.",
    "ncbi_link": "Cre: 2777477
ER: 13983
Mta1: 116870
Mta2: 23942
Mta3: 116871"
  },
  {
    "caption": "Western blot showing rescue of Mta123∆ ES cells by ectopic expression of Mta1, Mta2 or Mta3 from a transgene (TG). Total RNA Polymerase II acts as a loading control (αRNAPII). For all western blots molecular weight is indicated at left in kDa.",
    "ncbi_link": "Mta1: 116870
Mta2: 23942
Mta3: 116871"
  },
  {
    "caption": "Fold change in gene expression is plotted for different subsets of genes. All genes are plotted in black, while subsets of genes located nearest to ChIP-seq peaks for the indicated proteins +Chd4 and which show significant changes in expression compared to wild type cells are plotted in dashed coloured lines as indicated. The number of genes in each of the Mta categories are: all genes (32271), all differentially expressed (n=3701), Mta1+2+3 (n=1738), Mta1+2 (n=1460), Mta1 (n=1020) and Mta2 (n=924).",
    "ncbi_link": "Chd4: 107932
Mta1: 116870
Mta2: 23942"
  },
  {
    "caption": "Genes associated with indicated GO terms plotted by fold change in expression in Mta123∆ ES cells (x-axis) or Mbd3∆ ES cells (y-axis). Genes are coloured if they are differentially expressed (log2 fold-change > 1 and adjusted p-value < 0.05) in either comparison as indicated. The dotted lines show the fold-change cut-off of 2. GO-terms were identified using David v.6.8 using a Benjamini score with a cutoff of 0.05.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Genes associated with core NuRD peaks, with an MTA-only peak, with a Chd4 peak and an MTA-peak but not an Mbd3 peak (Chd4+Mta-Mbd3 genes), or with an MTA-peak but not a Chd4 peak (MTA-only genes) were divided into quartiles based upon expression levels in wild type cells. Change in gene expression is plotted on the x-axis and calculated significance of the expression change on the y-axis. Those genes significantly misexpressed (|log2FC|>1; p≤0.05) are indicated in red, genes showing no significant change are plotted in black. The percentage of genes within each quartile which is significantly misexpressed is indicated at the top of each plot.",
    "ncbi_link": "Chd4: 107932
Mbd3: 17192"
  },
  {
    "caption": "Phase contrast pictures of ES cells of indicated genotypes after 5 days in neuroectoderm differentiation conditions (N2B27). White arrowheads in the Mbd3∆ panel indicate pockets of ES-like cells. Scale bars represent 100 µm.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Expression of indicated genes in the neuroectoderm differentiation time course was measured by RT-qPCR in Control (green) Mta123∆ (magenta) or Mbd3∆ (blue) ES cells. N ≥ 3 biological replicates, error bars indicate SEM.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Comparison of expression data for wild type, Mbd3∆ or Mta123∆ ES cells in self-renewing (2i) conditions or after 48 hours in differentiation conditions (48h N2B27) with mouse embryonic single cell RNA-seq data Larger shading encloses biological replicates, smaller circles represent individual cells.",
    "ncbi_link": "Mbd3: 17192"
  },
  {
    "caption": "Composite images of representative chimaeric embryos made with control (Mta1Flox/∆Mta2+/+Mta3Flox/Flox) or Mta123∆ ES cells. ES-derived cells express the Kusabira Orange fluorescent marker. Sox2 indicates epiblast cells and Cdx2 is expressed in trophectoderm cells. Arrows indicate examples of K-Orange expressing cells in the mutant embryos. Scale bars = 20µm.",
    "ncbi_link": "Mta1: 116870
Mta2: 23942
Mta3: 116871"
  },
  {
    "caption": "(Top) Number of K-Orange expressing cells observed in chimaeric embryos obtained using control ES cells, Mta123∆ ES cells, or Mta123∆ ES cells in which Mta2 was reintroduced on a constitutively expressed transgene (Mta123∆+Mta2TG). P-values calculated using a two-tailed t-test. (Middle) Mean number of K-Orange cells per embryo separated by Sox2 expression. P-values calculated using a two-tailed t-test. (Bottom) Number of K-Orange and Caspase-3 positive cells per embryo. P-values calculated using a one-tailed t-test: *P < 0.05, ****P < 0.0001, \"ns\" = not significant.",
    "ncbi_link": "Mta2: 23942"
  },
  {
    "caption": "(E) Quantitative RT-PCR (qRT-PCR) of μGLT, αGLT, and AID from siControl- and siPhf5a-treated samples. The values are presented as mean ± sd (n=3).",
    "ncbi_link": "αGLT: 
μGLT: 
AID: 11628
Phf5a: 68479"
  },
  {
    "caption": "(B) Southern blots of the IgH/c-Myc translocation assay using genomic DNA extracted from CIT-stimulated CH12F3-2A cells treated with the siRNAs shown at the bottom of each panel. Numbers on the top indicate gel lanes. (C) Frequency of IgH/c-Myc chromosomal translocations derived from the number of translocations detected in the total number of PCR reactions per sample (Boboila et al., 2012b). The values are presented as mean ± sd (n=3). Statistical significance was assessed by two tailed unpaired Student's t-test (** p ≤ 0.01, *** p ≤ 0.001). ",
    "ncbi_link": "c-Myc: 
IgH: 111507"
  },
  {
    "caption": "(B) Effect of Phf5a knockdown on I-SceI-induced NHEJ. Plot represents the GFP-positive cells obtained by FACS analysis after co-transfection of the I-SceI expression plasmid and the indicated siRNAs into a cell line harboring the NHEJ reporter construct. The values are presented as mean ± sd (n=3). Statistical significance was evaluated against corresponding siControl by two-tailed unpaired Student's t-test (*** p ≤0.001).",
    "ncbi_link": "Phf5a: 68479"
  },
  {
    "caption": "(C) Top: schematic diagram of the position of the ChIP assay PCR products specific to the S region. Bottom: ChIP assay of the indicated DNA repair proteins using CIT-stimulated CH12F3-2A cells transfected with siControl or siPhf5a. The values are presented as mean ± sd (n=3). Statistical significance was evaluated in reference to siControl by two-tailed unpaired Student's t-test (*p ≤ 0.05, ** p ≤0.01, *** p ≤0.001).",
    "ncbi_link": "Phf5a: 68479"
  },
  {
    "caption": "(C) Western blot analysis of the whole cell extract from CIT-stimulated CH12F3-2A cells transfected with the indicated siRNAs. Expression of various proteins including AID, variant H2As and Ku80 were not decresed by Phf5a KD. (ns, non-specific)",
    "ncbi_link": "Phf5a: 68479"
  },
  {
    "caption": "(C) CH12F3-2A cells were transfected with WT Phf5a or its mutants (Phf5aR-MF) along with siRNA against Phf5a. An anti-Flag antibody was used to immunoprecipitate and immunodetect Phf5aR-MF. An anti-Phf5a immunoblot confirmed the knockdown efficiency of the endogenous Phf5a. The antibodies used to detect the co-associated proteins are indicated next to the respective blot.",
    "ncbi_link": "Phf5a: 68479"
  },
  {
    "caption": "(C) H2A.Z ChIP assay was performed using CH12F3-2A cells transfected with indicated siRNA and the Phf5a expression constructs. The data are compiled from 2 experiments and presented relative to siControl treated sample, which was set as 100. The error bars represent the mean ± sd.",
    "ncbi_link": "Phf5a: 68479"
  },
  {
    "caption": "Phloroglucinol staining of wild-type seedlings inoculated with PTI-inducing Pst DC3000 hrcC-, virulent Pst DC3000, and avirulent Pst DC3000 (AvrRpm1) and Pst DC3000 (AvrRpt2). Data information: Twelve-day-old seedlings were flood-inoculated with P. syringae at 108 cfu/ml in (A hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422
hrcC: 1183025"
  },
  {
    "caption": "B Phloroglucinol staining of wild-type adult leaves inoculated with PTI-inducing Pst DC3000 hrcC-, virulent Pst DC3000, and avirulent Pst DC3000 (AvrRpm1) and Pst DC3000 (AvrRpt2). The upper images are enlarged ones of the lower boxes at 2 dpi. Scale bars, 100 μm. Data information Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml in (B hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation; IS, infected site; UIS, uninfected site.",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422
hrcC: 1183025"
  },
  {
    "caption": "C Quantification of lignin content in pathogen-treated seedlings Data are shown as means ± SD (n = 4; 20-30 seedlings each). Data information: Twelve-day-old seedlings were flood-inoculated with P. syringae at 108 cfu/ml Significant differences are indicated by different letters (Tukey's HSD test; P < 0.05) Experiments were repeated 3 times with similar results. hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422
hrcC: 1183025"
  },
  {
    "caption": "D Quantification of lignin content in pathogen-treated wild-type leaves Data are shown as means ± SD (n = 4; 3-9 leaves each). Data information: Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml Significant differences are indicated by different letters (Tukey's HSD test; P < 0.05) Experiments were repeated 3 times with similar results. hrcC-, Pst DC3000 hrcC-; DC3000, Pst DC3000; AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422
hrcC: 1183025"
  },
  {
    "caption": "E Quantification of lignin content in wild-type leaves treated with different titers of Pst DC3000 (AvrRpm1). Data are shown as means ± SD (n = 4; 3-9 leaves each). Six-week-old leaves were syringe-infiltrated with P. syringae at the indicated titers in (E). Significant differences are indicated by asterisks (t test; *P < 0.05; **P < 0.01; ***P < 0.001). Experiments were repeated 3 times with similar results. dpi, days post-inoculation",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "F Quantification of lignin content in wild-type and rpm1-3 rps2-101c leaves treated with avirulent bacteria. Data are shown as means ± SD (n = 4; 3-9 leaves each). Six-week-old leaves were syringe-infiltrated with P. syringae at 108 cfu/ml Significant differences are indicated by asterisks (t test; *P < 0.05; **P < 0.01; ***P < 0.001). Experiments were repeated 3 times with similar results. AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422
rpm1: 819889
rps2: 828715"
  },
  {
    "caption": "B Quantification of lignin content in palQ leaves after the indicated treatments and pathogen infection. Data are shown as means ± SD (n = 4; 3-9 leaves each). Data information: Six-week-old leaves were inoculated with Pst DC3000 (AvrRpm1) at 108 cfu/ml for experiments. Different letters indicate significant differences (Tukey's HSD test; P < 0.05). Experiments were repeated 3 times with similar results. M, mock; PA, piperonylic acid; CA, coniferyl alcohol; dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "C Measurements of Pst DC3000 (AvrRpm1) growth. Data are shown as means ± SD (n = 3). Data information: Six-week-old leaves were inoculated with Pst DC3000 (AvrRpm1) at 105 cfu/ml for growth assays Different letters indicate significant differences (Tukey's HSD test; P < 0.05). Experiments were repeated 3 times with similar results. M, mock; PA, piperonylic acid; CA, coniferyl alcohol; dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "D Cell death phenotypes of leaves inoculated with Pst DC3000 (AvrRpm1). E Quantification of leaves (n ≥ 30) with spreading cell death as in (D). Data information: Six-week-old leaves were inoculated with Pst DC3000 (AvrRpm1) at 105 cfu/ml for growth assays M, mock; PA, piperonylic acid; CA, coniferyl alcohol; dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "F Quantification of total and free SA in Col-0 and palQ leaves after the indicated treatments and pathogen infection. Data are shown as means ± SD (n = 5; 6 leaves each). Data information: Six-week-old leaves were inoculated with Pst DC3000 (AvrRpm1) at 108 cfu/ml for experiments. Different letters indicate significant differences (Tukey's HSD test; P < 0.05). Experiments were repeated 3 times with similar results. M, mock; PA, piperonylic acid dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "A Colonization patterns of GFP-Pst DC3000 and Pst DC3000 (AvrRpt2) in wild-type plants. Data information: Leaves were inoculated with GFP-labeled bacteria at 108 cfu/ml for 2 days. IS, infected site; UIS, uninfected site. White dash lines indicate the boundary between IS and UIS. Scale bars, 100 μm",
    "ncbi_link": "AvrRpt2: "
  },
  {
    "caption": "B Time-lapse images of GFP-Pst DC3000 and Pst DC3000 (AvrRpt2) captured at 0 (magenta), 15, (yellow), and 30 (green) sec Time in seconds in the movies is shown at the top of images. Blue color was used for chlorophyll autofluorescence. Data information: Leaves were inoculated with GFP-labeled bacteria at 108 cfu/ml for 2 days. Scale bars, 10 μm",
    "ncbi_link": "AvrRpt2: "
  },
  {
    "caption": "C Colonization patterns of GFP-Pst DC3000 (AvrRpt2) in wild-type and palQ plants after PA and CA pretreatments. Data information: Leaves were inoculated with GFP-labeled bacteria at 108 cfu/ml for 2 days. M, mock; PA, piperonylic acid; CA, coniferyl alcohol; IS, infected site; UIS, uninfected site. White dash lines indicate the boundary between IS and UIS. Scale bars, 100 μm",
    "ncbi_link": "AvrRpt2: "
  },
  {
    "caption": "B Cross-sections of CANBD- and Pst DC3000 (AvrRpm1)-treated leaves. Data information: Bacterial inoculum was at 108 cfu/ml. hpi, hours post-inoculation Scale bars, 40 μm",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "D CADMAC-incorporated lignin deposition in the GFP-Pst DC3000 (AvrRpt2)-infected site at 2 dpi. Data information: Bacterial inoculum was at 108 cfu/ml. IS, infected site; UIS, uninfected site DC3000, Pst DC3000; AvrRpt2, Pst DC3000 (AvrRpt2); Chl, chlorophyll. White dash lines indicate the boundary between IS and UIS. Scale bars, 100 μm",
    "ncbi_link": "AvrRpt2: "
  },
  {
    "caption": "E Cellular observation of CADMAC-incorporated lignin formation against infecting GFP-Pst DC3000 (AvrRpt2). Data information: Bacterial inoculum was at 108 cfu/ml. hpi, hours post-inoculation Scale bars, 20 μm",
    "ncbi_link": "AvrRpt2: "
  },
  {
    "caption": "A Time course expression profiles of CASPLs in response to Pst DC3000 (AvrRpm1) treatment. Analysis was based on the Genevestigator database (http://www.genevestigator.ethz.ch/). The darker color corresponds to stronger expression. ND, not determined.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "Quantification of lignin content in wild-type and caspl mutant leaves after Pst DC3000 (AvrRpm1) inoculation. ata are shown as means ± SD (n = 4; 3-9 leaves each). ata information: Different letters indicate significant differences (Tukey's HSD test; P < 0.05). Experiments were repeated 3 times with similar results. AvrRpm1, Pst DC3000 (AvrRpm1); dpi, days post-inoculation.",
    "ncbi_link": "caspl: 844316
AvrRpm1: 877422"
  },
  {
    "caption": "C Cell death phenotypes of leaves inoculated with Pst DC3000 (AvrRpm1). Data information: AvrRpm1, Pst DC3000 (AvrRpm1) dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "D Quantification of leaves (n ≥ 30) with spreading cell death after Pst DC3000 (AvrRpm1) inoculation. dpi, days post-inoculation.",
    "ncbi_link": "AvrRpm1: 877422"
  },
  {
    "caption": "E Measurements of Pst DC3000 (AvrRpm1) and Pst DC3000 (AvrRpt2) growth. Data are shown as means ± SD (n = 3). Data information: Different letters indicate significant differences (Tukey's HSD test; P < 0.05). Experiments were repeated 3 times with similar results. AvrRpm1, Pst DC3000 (AvrRpm1); AvrRpt2, Pst DC3000 (AvrRpt2); dpi, days post-inoculation.",
    "ncbi_link": "AvrRpt2: 
AvrRpm1: 877422"
  },
  {
    "caption": "F Colonization patterns of GFP-Pst DC3000 (AvrRpt2) in caspl mutant plants. IS, infected site; UIS, uninfected site. White dash lines indicate the boundary between IS and UIS. Scale bars, 100 μm.",
    "ncbi_link": "AvrRpt2: 
caspl: 827238"
  },
  {
    "caption": "A Visualization of CASPL4D1 proteins and lignin by mCherry and CADMAC fluorescence. Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1). mCh, mCherry; Chl, chlorophyll; hpi, hours post-inoculation. Scale bars, 20 μm (A)",
    "ncbi_link": "mCherry: 
CASPL4D1: 818538
AvrRpm1: 877422"
  },
  {
    "caption": "B Magnified views of CASPL4D1 and lignin localization. Images in boxes were enlarged in the 2nd to 4th columns. Arrows indicate lignin deposition between cells. Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1). mCh, mCherry; Chl, chlorophyll; hpi, hours post-inoculation. Scale bars 10 μm (B).",
    "ncbi_link": "mCh: 
mCherry: 
CASPL4D1: 818538
AvrRpm1: 877422"
  },
  {
    "caption": "C Relative fluorescence intensity profiles of CASPL1D1 (mCherry) and lignin (CADMAC) across transects indicated by dotted lines Data information: pCASPL4D1::CASPL4D1-mCherry plants were pretreated with CADMAC and then inoculated with Pst DC3000 (AvrRpm1).",
    "ncbi_link": "mCherry: 
CASPL4D1: 818538
AvrRpm1: 877422"
  },
  {
    "caption": "D) Bar chart showing relative DsRed expression  of sensors containing different mutated target sequence of miR-17 Additionally, a sensor containing no target (n.t.) and two wildtype (WT) T17 target sites with 1x and 4x repeats were tested. Two-tailed unpaired t-tests were performed to compare H1  and  HES-2  for each sensor. *P-values < 0.01, were considered very significant (**), < 0.02 significant (*) and > 0.5 not significant.. Representative scatterplots of HES-2 are shown on top. Data information: Each bar in D corresponds to mean +/- s.d. from at least three biological replicates.",
    "ncbi_link": "miR-17: 406952"
  },
  {
    "caption": "C) Combinatorial screen. Computational combinatorial screening  of Act1MAX and Act2MAX using the model depicted in A (left). Experimental  combinatorial screening in H1  (middle) with circuit schematic on top. Two different Act1-Act2  circuit configurations are depicted: PIT2-tTA (left) and rtTA-PIT2 (right). Calculated FF4  and Output levels are shown for On, Off and Off/On (FF4) or On/Off (Output). Color plots show normalized mCitrine   (left) and mCherry   (right) expression  levels for each Act1-Act2  combination. Color bars show lowest and highest expression  range on a linear scale with median as the midpoint D) Correlation plots with calculated values on X axis (Model) and experimental data on Y axis (Data). A linear regression model (y = a + b*x) was used to compare experimental data with model predictions. Linear fit and coefficient of determination (R2) as indicated. PIT2-tTA circuit (black), rtTA-PIT2 circuit (red).",
    "ncbi_link": "FF4: 
mCitrine: 
Act2: 6351
Act1: 10758"
  },
  {
    "caption": "C) Bar chart showing the performance of circuit 1 - 3 in H1, HES-2 and HEK293. mCitrine   (top) and mCherry   (bottom) expression  was normalized to internal Ef1a-iRFP  control (rel.U.) (left) and further normalized to maximal mCitrine   (circuit 2) (top) or maximal mCherry   (bottom) (rel.U./Ctrl) (right). Samples below detection limit are labelled with b.d. Data information: Each bar show mean ± s.d. of at least three biological replicates.",
    "ncbi_link": "iRFP: 
mCitrine: 
Ef1a: 1915"
  },
  {
    "caption": "D) Bar chart showing performance of circuit 1 in response to administration of miRNA mimics in H1  (left) and HEK293  (right). First sample (with profile + + - - - for H1  and - - - - - for HEK292) has no miRNA administered. For the other samples, miRNA dose with highest change in response has been selected from miRNA titration experiments Maximal mCitrine  and mCherry  levels (as calculated in B) are depicted as yellow and red dashed lines, respectively. Chart is shown in a base 10 logarithmic scale. Data information: Each bar show mean ± s.d. of at least three biological replicates.",
    "ncbi_link": "mCitrine: "
  },
  {
    "caption": "E) Bar chart showing fine tuning of output using miSFITs library. Shown are FF4  / mCitrine  (top) and Output / mCherry  (bottom) of circuit 1 and 3 for different T17 variants. Data were normalized to control circuits. Data information: Each bar show mean ± s.d. of at least three biological replicates.",
    "ncbi_link": "FF4: 
mCitrine: "
  },
  {
    "caption": "A) Circuit schematics (left). Chart shows normalized Output production in response to changing amounts of plasmids encoding Act2, tTA (left) and PIT2 (right). Two transactivator constructs have been tested, onecontains miR302a/b target sites (Off), the other by mock  miRFF3/FF6  target sites (ON). Data information: Charts show mean ± s.d. of at least three biological replicates.",
    "ncbi_link": "FF6: 
Act2: 6351
miR302a: 407028
miRFF3: 7033"
  },
  {
    "caption": "Two-photon representative images of wild-type and Nlrp3-/- mice (5 and 15 months old). Scale bar: 20µm. Quantification of morphological parameters for wild-type and Nlpr3-/- mice after LPS injection",
    "ncbi_link": "Nlrp3: 216799
Nlpr3: 216799"
  },
  {
    "caption": "Representative cortical images of MXO4 staining for APP and APP/Nlrp3-/- 15 months old mice. Scale bar: 50µm.",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Cortical amyloid plaque number and size quantification, and Amyloid-beta1-40 and 1-42 ELISA quantification for APP and APP/Nlrp3-/- mice (5 and 15 month old)",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Two-photon images of microglia (e-GFP) cells clustering around amyloid plaque for APP and APP/Nlrp3-/- (5 and 15 months old). Scale bar: 20µm b) Quantification of morphological parameters in (a) (mean of 5-6±SEM).",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Flow cytometry plots from APP and APP/Nlrp3-/- mice (15 months old), cells were gated on CD11b and MXO4 after microglia isolation. d) Relative Aβ microglia uptake quantification",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Two-photon microglia (e-GFP) images from APP and APP/Nlrp3-/- in areas free of plaque (5 and 15 months old mice). Scale bar: 20µm Quantification of APP and APP/Nlrp3-/- morphological parameters for microglia in areas free of plaque",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Iba-1 (green), CD169 (red) and MXO4 staining in plaque-associated areas (cortex and hippocampus) of 5 and 15 months old of APP and APP/Nlrp3-/-. Note the colocalization between Iba-1 and CD169 (white arrows) in APP 15-month-old mice 2 days post LPS injection. Scale bar: 20µm",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "Iba-1, Ki67 and DAPI staining in the cortex and hippocampus of wild-type and Nlrp3-/- (5 and 15 months old). Microglia proliferates upon LPS injection (white arrows). Non-microglia cells proliferation was observed as well (yellow arrows) Scale bar: 20µm. Quantification of microglial proliferation in cortex (left panel) and hippocampus (right panel) (mean of 5±SEM; two-way ANOVA followed by Tukey's post hoc test, *p<0.05, **p<0.01, ***p<0.001).",
    "ncbi_link": "Nlrp3: 216799"
  },
  {
    "caption": "Iba-1, Ki67 and MXO4 staining in the cortex and hippocampus of APP and APP/Nlrp3-/- (5 and 15 months old). Microglia proliferates upon LPS injection (white arrows). Non-microglia cells proliferation was observed as well (yellow arrows). Scale bar: 20µm Quantification of microglial proliferation in cortex (left panel) and hippocampus (right panel)",
    "ncbi_link": "APP: 351
Nlrp3: 216799"
  },
  {
    "caption": "A Representative images of GFP-gephyrin and GFP-G375D, expressed in hippocampal neurons at 9 + 4 days in vitro. Inset shows higher magnification. Scale bar = 20 µm.B Relative distribution of cluster density of gephyrin variants on dendrites from transfected neurons. Number of gephyrin clusters in each dendrite is normalized to 20 µm segments.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "C Representative segments of dendrites expressing GFP-gephyrin or GFP-G375D and immunostained with the presynaptic marker VGAT. Arrowheads show co-localization of gephyrin and VGAT clusters. Scale bar = 10 µm.D Quantification of co-localization between gephyrin and VGAT clusters (gephyrin-VGAT 77.4±2.9 %, G375D-VGAT 30±4.4 %). 31 GFP-gephyrin and 30 GFP-G375D neurons from three independent cultures were used for quantifications. Results are expressed as mean ± SEM",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "A Representative dendritic segment of a neuron expressing GFP-G375D and 3B11-immunostained endogenous gephyrin (red).B Quantification of density and (C) size of endogenous gephyrin clusters in neurons expressing GFP, GFP-G375D or non-transfected neighboring neurons. 20 GFP-G375 and non-transfected neurons and 15 GFP-expressing neurons from three independent cultures were used for quantifications. Results are expressed as mean ± SEM and data were analyzed by t-test.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "A Representative neurons expressing myc-tagged gephyrin or G375D and pHluorin-tagged GABAAR γ2. Surface-expressed γ2-subunits were immunolabelled with GFP-antibodies in red, and the pHluorin-fluorescence (total γ2 levels) are shown in green.B Size and C fluorescence (fl.) intensity of surface-expressed γ2 clusters in myc-gephyrin and myc-G375D-expressing dendrites (n = 20 myc-gephyrin and 21 myc-G375D neurons in B and 18 myc-gephyrin and myc-G375D neurons in C)D Mean γ2-pHluorin fluorescence in myc-gephyrin and myc-G375D-expressing dendrites (n = 20 and 18 myc-gephyrin and myc-G375D expressing neurons).E Number of surface γ2 clusters on dendrites normalized to 20 µm segments (n = 18 myc-gephyrin and myc-G375D expressing neurons). At least three independent cultures were used for each experiment. Results are expressed as mean ± SEM; Data were analyzed by t-test.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "F Representative traces of miniature recordings on cultured hippocampal neurons transfected either with GFP-gephyrin or GFP-G375D.G mIPSC amplitudes from neurons expressing GFP-gephyrin or GFP-G375D. Numbers show analyzed cell-numbers. Data were analyzed by one-way ANOVA and post-hoc Tukey test.H Frequency of the mIPSCs from neurons expressing GFP-gephyrin or GFP-G375D. The horizontal line within the boxes indicates the median frequency for the represented condition (bottom/top boundary indicates the 25th /75th percentile). Top and bottom error bars indicate the 90th and 10th percentiles, respectively. Analysis by Kruskal-Wallis test followed by post-hoc Mann-Whitney test.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "A Western blot of HEK293 cells expressing GFP-tagged gephyrin or G375D using GFP-specific and polyclonal gephyrin antibodies. Note that both gephyrin variants are stably expressed and show no degradation in the cells. Asterisk in the poly-gephyrin blot shows endogenous gephyrin.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "B SDS-PAGE of E. coli expressed and purified 6His-gephyrins and CD spectra. Mean residue ellipticity of gephyrin and G375D show profiles with minima at 208 nm and 222 nm.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "C Size-exclusion chromatography of purified 6His-gephyrin and isolated E-domain variants. Full-length gephyrins and isolated E-domains were loaded onto a Superose 6 gel filtration column and elution of the protein was monitored by measuring absorbance at 280 nm (mAU, milliabsorbance units).",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "D Co-immunoprecipitation of HEK293 cell lysates expressing myc-tagged gephyrin together with GFP-tagged gephyrin or G375D using myc-specific antibodies. Control IgG were used to show specificity of the assay.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "B Representative pulldown-experiment and quantification of 6His-tagged gephyrin and G375D using immobilized α3-peptide. 6His-tagged gephyrin variants were expressed in E. coli cells, purified to homogeneity and incubated with α3-peptides immobilized to NeutrAvidin beads. n = 3, normalized to 6His-gephyrin. 38.9±1.5% G375D were pulled down.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "C Representative SPR sensograms of 6His-gephyrin and 6His-G375D binding to immobilized GABAAR α3-peptide. Response units are plotted against time. Injected gephyrin concentrations were 0.5, 2, 10, 25, 40 µM.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "D SPR binding isotherms of a representative experiment as in C. Calculated KD values of 3.2 and 10 µM for gephyrin and G375D, respectively, are indicated by vertical lines. The experiment was repeated three times with two independently purified protein batches and two sensor chips.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "E Representative ITC binding isotherms of the cytoplasmic loop of the GlyR ß-subunit (GlyR-ßL, residue 378-426) and 6His-tagged gephyrin or G375D. The GlyR-ßL-gephyrin binding data (black) were fitted in a two-side model, whereas G375D binding could only be fitted to a single binding site. Dissociation constants KD and stoichiometry (N = number of binding sites) are given for each binding component. n = 5 from two independently purified protein batches. Results are expressed as mean ± SEM.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "A Biosynthesis pathway of Moco with all stable intermediates. Gephyrin G- and E-domain catalyze the last two steps as depicted.B In vitro Moco-synthesis assay using 150 pmol purified 6His-tagged gephyrins. D580A is an activity-deficient gephyrin mutation previously identified in Moco-deficient patients (Reiss et al., 2011). Assays without the addition of gephyrin (-gephyrin) or molybdenum (-Mo) served as internal controls of the assay (see also (Belaidi & Schwarz, 2013)).C Experiment as in B but with pre-incubation of 6His-gephyrin/G375D in a 1:1 ratio to simulate the heterozygous mutation. n = at least 3 with two independently purified protein batches. Results are expressed as mean ± SEM.",
    "ncbi_link": "gephyrin: 10243"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were transfected to transiently express centrin1-GFP (red) and EB3-mCherry (green) and video-recorded at the contact site with the glass coverslip (left) and at the centrosome (right). Scale bar: 3 µm.",
    "ncbi_link": "GFP: 
mCherry: 
centrin1: 1068
EB3: 22924"
  },
  {
    "caption": "IIA1.6 B lymphoma cells were transfected to transiently express centrin1-VCA-GFP (bottom) or centrin1-GFP (top) as control prior to be fixed and stained for α-tubulin (left column) and F-actin (middle column). The GFP signal of centrin1 or centrin1-VCA is shown in the right column to illustrate the proper centrosome targeting. Scale bar: 3 µm.",
    "ncbi_link": "GFP: 
centrin1: 1068"
  },
  {
    "caption": "Histograms show the quantifications of the amount of polymerized fluorescent tubulin (right) and filamentous actin at the centrosome (left). Values correspond to the fraction of fluorescence in a 2-micron-wide area around the centrosome relative to the total fluorescence in the cell. Measurements were pooled from 3 independent experiments; centrin1-GFP: n= 88, centrin1-VCA-GFP: n= 87. Errors bars represent standard deviations. P values were calculated with Mann-Whitney test.",
    "ncbi_link": "GFP: 
centrin1: 1068"
  },
  {
    "caption": "Percentage differences of F-actin and microtubule fluorescence intensities at the centrosome were compared in cells transfected either with centrin1-VCA-GFP or with centrin1-GFP. Errors bars represent standard deviations. P values were calculated with one-sample t-test (i.e. comparison to a theoretical mean of \"0\").",
    "ncbi_link": "GFP: 
GFP.: 
centrin1: 1068"
  },
  {
    "caption": "The graph shows the variations of the total amount of tubulin per cell with respect to the content of actin at the centrosome. The two lines correspond to linear regressions of the two sets of data relative to cells transfected with centrin1-VCA-GFP or centrin1-GFP.",
    "ncbi_link": "GFP: 
centrin1: 1068"
  },
  {
    "caption": "Two sets of representative images showing fluorescent microtubules and actin filaments assembled from isolated centrosomes. Centrosomes were isolated from Jurkat cells expressing centrin1-GFP. Upper and lower lines show actin filaments and microtubules radiating from two distinct centrosomes with low (top) and high (bottom) densities of actin filaments. Scale bars: 10 μm.",
    "ncbi_link": "GFP.: 
centrin1: 1068"
  },
  {
    "caption": "RPE1 cells stably expressing centrin1-GFP were plated for 3 h on coverslips coated with different ratios (100:0; 50:50 or 1:99) of fibronectin and PLL-PEG prior to fixation and staining for F-actin (top line and magnified views around centrosome below. Scale bars: 10 µm and 2 µm, respectively) and α-tubulin (bottom line. Scale bar: 10 µm).",
    "ncbi_link": "GFP: 
centrin1: 1068"
  },
  {
    "caption": "B) Binding affinity  of CodB  for cytosine  as measured using the thermostability assay. Cytosine  was titrated into detergent solubilised membranes   from cells overexpressing CodB. The  Kd  was estimated to be 51 ± 9 µM. The measurements are the average of 4 independent titrations with error bars of the s.e.m.",
    "ncbi_link": "CodB: 57310904"
  },
  {
    "caption": "Western blot of CHIR-treated Hoxb8-FL WT and Bax-/-Bak-/- cells using the indicated antibodies.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "WT and Bax-/-Bak-/- Hoxb8-FL cells were treated for up to 8h with 500 nM CHIR and p21 mRNA levels were compared to Hprt in response to CHK1-inhibition by real-time RT-qPCR. Bars represent means ± S.D. of independent experiments (n=4-6), performed in duplicates.",
    "ncbi_link": "Hprt: 
Bak: 12018
Bax: 12028
p21: 12575"
  },
  {
    "caption": "CD34+ cells were transduced with a BCL2-encoding lentivirus or a control virus, along with IRES-GFP with a MOI of 10 for two consecutive days, followed by CHK1i application for 48 h. Survival was assessed using Nicoletti staining and flow cytometry.",
    "ncbi_link": "GFP: 
BCL2: 596"
  },
  {
    "caption": "Colony formation potential of human CD34+ HSPCs transduced with empty control or BCL2 encoding virus. Colonies were counted 10 days post seeding of 1000 CD34+ cells per plate/sample. \"Myeloid colonies\" include granulocyte/monocyte, monocyte, granulocyte and GEMM (granulocyte, erythroid, monocyte/macrophage and megakaryocyte) colonies.",
    "ncbi_link": "BCL2: 596"
  },
  {
    "caption": "Representative pictures of E13.5 and E18.5 embryos of the indicated genotypes. Scale bar E13.5 = 1 mm, E18.5 = 5 mm. Quantification of fetal liver cell number at E13.5. Bars represent means ± S.E.M. (N=4 for Chk1fl/+, N=3 for Chk1fl/+ Vav-Cre and N=4 for Chk1fl/- Vav-Cre).",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Representative H&E-staining of fetal liver sections from E13.5 embryos. Black arrows indicate lack of erythroid cells in the blood vessels of Chk1fl/- Vav-Cre fetal livers. Scale bar = 500 µM.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Single cell suspensions of fetal livers from Chk1fl/+, Chk1fl/+ Vav-Cre and Chk1fl/- Vav-Cre embryos were stained with antibodies recognizing ckit, CD71, Ter119 or CD45 to assess primitive and definitive erythropoiesis by flow cytometry. Large 'EryA' erythroblasts (CD71high Ter119high FSChigh), smaller, more mature 'EryB' erythroblasts (CD71high Ter119high FSClow); most mature erythroblast subset is EryC (CD71low Ter119high FSClow). Bars represent means ± S.E.M. ctrl N=5 (pooled N=4 Chk1fl/+ and N=1 Chk1fl/+ Vav-Cre), N=3 for Chk1fl/- Vav-Cre.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Representative dot-plots of the LSK cell phenotype of Chk1fl/+ and Chk1fl/- Vav-Cre embryos observed in E13.5 fetal livers and relative distribution / absolute numbers of LKhi and LSKhi cells, as well as LKlow and LSKlow cells, found in the fetal liver on E13.5. Bars represent means ± S.E.M. N=4 for Chk1fl/+ and N=4 for Chk1fl/- Vav-Cre.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Colony formation potential of FACS-sorted LSK cells (left panel, N=4 for Chk1fl/+ and N=5 for Chk1fl/- Vav-Cre) and total fetal liver cells (right panel, N=3 for Chk1fl/+ and N=6 for Chk1fl/- Vav-Cre) in methyl-cellulose assays. Bars represent means ± S.E.M.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Flow cytometric analysis of LSKhi or LSKlow cells stained with antibodies specific for CD34 and Flt3 (N=4 for Chk1fl/+ and N=4 for Chk1fl/- Vav-Cre), to discriminate LT- and ST-HSC from MPP within the LSK-subset. Bars represent means ± S.E.M.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of fetal liver cryosections of the indicated genotypes at E13.5 and quantification. Scale bar 100x = 200 µM, 400x = 50 µM. The percentage of TUNEL+ area/field was assessed across three random fields from two control (Chk1fl/+) and two knock-out embryos (Chk1fl/- Vav-Cre) using ImageJ, as reported by us before (60). Bars represent means ± S.D.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Total fetal liver cell suspensions of Chk1fl/+ (+/+), Chk1fl/+ Vav-Cre (+/-) and Chk1fl/- Vav-Cre (-/-) E13.5 embryos were processed for Western blot analysis using the indicated antibodies. Each lane represents samples isolated from an individual littermate embryo.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Total E13.5 fetal liver cells were processed for intracellular Ki67 staining in combination with cell surface antibody staining to discriminate LK (top panel) from LSK (lower panel) cells. Shown here are representative dot-plots of Ki67 and DAPI staining in LK and LSK cells, quantified in (E). Bars represent means ± S.E.M. N=4 for Chk1fl/+ and N=5 for Chk1fl/- Vav-Cre.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Representative dot-plots and quantification of E13.5 fetal liver LSKhi/LSKlow cell phenotypes observed in embryos of the indicated genotypes. N=21 for Chk1fl/+, N=5 for Chk1fl/- Vav-Cre, N=16 for Chk1fl/+ Vav-BCL2, N=5 for Chk1fl/- Vav-Cre Vav-BCL2, N=2 for p53-/- Chk1fl/+ and N=4 for p53-/- Chk1fl/- Vav-Cre.",
    "ncbi_link": "Chk1: 12649
Cre: 2777477
p53: 22059"
  },
  {
    "caption": "Flow cytometry-based analysis of LSK cells stained with antibodies specific for CD34 and Flt3, to discriminate LT- and ST-HSC from MPP within the LSK subset in fetal livers of embryos of the indicated genotypes. Left: N=25 for Chk1fl/+, N=7 for Chk1fl/+ Vav-Cre and N=7 for Chk1fl/- Vav-Cre. Right: N=16 for Chk1fl/+ Vav-BCL2, N=6 for Chk1fl/+ Vav-Cre Vav-BCL2 and N=5 for Chk1fl/- Vav-Cre Vav-BCL2.",
    "ncbi_link": "BCL2: 596
Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Analysis of the colony formation potential of E14.5 total fetal liver cells of the indicated genotypes in methylcellulose. N=3 for controls (pooled; 1 Chk1fl/+, 2 Chk1fl/+ Vav-Cre), N=3 for Chk1fl/- Vav-Cre and N=3 for Chk1fl/- Vav-Cre Vav-BCL2.",
    "ncbi_link": "BCL2: 596
Chk1: 12649
Cre: 2777477"
  },
  {
    "caption": "Three independent Chk1fl/fl mT/mG (coloured) and mT/mG (grey) Hoxb8-FL progenitor cell lines were transduced with a retroviral construct carrying Cre (pMIP-CRE-IRES-PURO) and monitored over time for GFP-expression. Shown here are three technical replicates per genotype. Additionally, Chk1fl/fl mT/mG Hoxb8-FL progenitor cells were FACS-sorted for GFP+ and dsRED+ cells 48h after transduction with the Cre-construct. Sorted cells were processed for western blotting using the indicated antibodies.",
    "ncbi_link": "mG: 
mT: 
Chk1: 12649
Cre: 2777477
CRE: 2777477
pMIP: 17339"
  },
  {
    "caption": "Chk1fl/fl Hoxb8-FL progenitor cells were transduced with a retroviral construct carrying Cre and GFP (pMIG-CRE-IRES-GFP). Cells were FACS-sorted 72h after transduction with the retroviral construct and processed for western blotting using the indicated antibodies.",
    "ncbi_link": "GFP: 
Chk1: 12649
Cre: 2777477
CRE: 2777477
pMIG: 17339"
  },
  {
    "caption": "Percentage of GFP+ cells indicative for CRE expression and recombination in the peripheral blood after tamoxifen administration by gavage (5 x 2 mg, 200 μl/mouse; daily). Bars represent means ± S.E.M. (Day 0 N=9/10, WT/Chk1fl/fl, Day 7 N=8/7, Day 14 N=3/3).",
    "ncbi_link": "Chk1: 12649
CRE: 2777477"
  },
  {
    "caption": "Quantification of Chk1-del PCR-product enrichment in DNA from GFP+ vs. Tomato+ bone marrow cells sorted on day 8 after first TAM administration. Transgenic Cre levels were quantified in parallel for reference. Bars represent means ± S.E.M. from n=5 mT/mG Vav-CreERT2 Chk1fl/fl mice.",
    "ncbi_link": "mG: 
mT: 
Chk1: 12649
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "Percentage of living LK or LSK-cells and (F) percentage of GFP+ LK or LSK-cells found in the bone marrow of mT/mG Vav-CreERT2 (WT) and mT/mG Vav-CreERT2 Chk1fl/fl (Chk1fl/fl) mice on day 8 or 15 post first TAM administration. Bars in (E)/(F) represent means ± S.E.M. (Day 8 N=8/8, WT/Chk1fl/fl, Day 15 N=7/8).",
    "ncbi_link": "mG: 
mT: 
Chk1: 12649
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "GFP+ (CRE) and Tomato+ (CRE-) total bone marrow cells were sorted on day 8 after first TAM-administration and processed for Western Blot using the indicated antibodies. Sorted cells from three animals - mT/mG Vav-CreERT2 (WT) and mT/mG Vav-CreERT2 Chk1fl/fl (Chk1fl/fl) - were pooled per lane.",
    "ncbi_link": "mG: 
mT: 
Chk1: 12649
CRE: 2777477
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "(A) Immunoblot analysis. Primary hepatocytes prepared from wild-type mice were infected with adenovirus expressing GFP or NBR1 under the CAG promoter for 48 hrs. Cell lysates were prepared and subjected to immunoblot analysis with the indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin. Data are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
NBR1: 17966"
  },
  {
    "caption": "(B) Real-time PCR. Total RNAs were prepared from primary hepatocytes described in (A). Values were normalized against the amount of mRNA in the hepatocytes expressing GFP. The experiments were performed three times. Data are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP.: "
  },
  {
    "caption": "(C) Immunofluorescence microscopy. Wild type hepatocytes were infected with LacZ or NBR1 adenovirus for 48 hrs and then immunostained with anti-p62 and anti-NBR1 antibodies. Each inset is a magnified image. Bars: 20 µm. The number and size of p62-bodies were measured in more than 100 cells. Data are shown as means ± s.e. ***P < 0.001 as determined by Welch's t-test.",
    "ncbi_link": "LacZ: 
NBR1: 17966"
  },
  {
    "caption": "(D) FRAP assay. Wild type hepatocytes cultured in glass-bottom plates were infected with GFP-NBR1 adenovirus for 48 hrs. The signal recovery after photobleaching was measured, quantified from at least three independent biological replicates, and is represented as means ± s.e. Bar: 1 µm.",
    "ncbi_link": "GFP: 
NBR1: 17966"
  },
  {
    "caption": "(A) Immunoblot analysis. Primary hepatocytes prepared from wild-type mice were infected with adenovirus expressing GFP-Nrf2 and GFP or NBR1 for 48 hrs. Total cell lysates were prepared and subjected to immunoblot analysis with the indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin. Data are shown as means ± s.e. **P < 0.01 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
NBR1: 17966
Nrf2: 18024"
  },
  {
    "caption": "(B) Immunoblot analysis. Primary hepatocytes prepared from p62f/f and p62f/f; Alb-Cre mice were infected with adenovirus against GFP or NBR1 for 48 hrs. Cytosolic and nuclear fractions were prepared and subjected to immunoblot analysis with the indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin (cytosolic proteins) or Lamin B (nuclear proteins). Data are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Alb: 11657
Cre: 2777477
NBR1: 17966
p62: 18412"
  },
  {
    "caption": "(C) Immunofluorescence microscopy. Primary hepatocytes from wild type mice were infected with adenovirus expressing GFP-Nrf2 and LacZ or NBR1 for 48 hrs. More than 100 cells were assayed for the nuclear signal of Nrf2. Data are shown as means ± s.e. ***P < 0.001 as determined by Welch's t-test. Bars: 10 µm.",
    "ncbi_link": "GFP: 
LacZ: 
NBR1: 17966
Nrf2: 18024"
  },
  {
    "caption": "(D) Total RNAs were prepared from primary hepatocytes described in (B). Values were normalized against the amount of mRNA in the p62f/f hepatocytes expressing GFP. The experiments were performed at least three times. Data are are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
p62: 18412"
  },
  {
    "caption": "(A) Immunofluorescence microscopy. Primary hepatocytes prepared from p62f/f mice were infected with or without adenovirus Cre recombinase for 48 hrs and then additionally infected with adenovirus LacZ or NBR1. 24 hrs after the infection, the hepatocytes were immunostained with anti-Keap1, anti-p62 and anti-NBR1 antibodies. Each inset is a magnified image. Bars: 10 µm.",
    "ncbi_link": "LacZ: 
Cre recombinase: 2777477
NBR1: 17966
p62: 18412"
  },
  {
    "caption": "(C) Primary hepatocytes prepared from p62f/f; Alb-Cre mice were co-infected with adenovirus GFP or NBR1 in combination with wild-type p62 or the mutants for 48 hrs. Cell lysates were prepared and subjected to immunoblot analysis with the indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin. Data are shown as means ± s.e. *P < 0.05, **P < 0.01, and ***P < 0.001 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Alb: 11657
Cre: 2777477
NBR1: 17966
p62: 18412"
  },
  {
    "caption": "(D) RT qPCR analysis. Total RNAs were prepared from hepatocytes described in (C). Values were normalized against the amount of mRNA in the hepatocytes expressing GFP. The experiments were performed three times. Data are shown as means ± s.e. *P < 0.05, and **P < 0.01 as determined by Welch's t-test.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) Immunoblot analysis. Primary hepatocytes prepared from Nrf2f/f and Nrf2f/f; Alb-Cre mice were infected with adenovirus expressing GFP or NBR1 for 48 hrs. Cytosolic and nuclear fractions were prepared and subjected to immunoblot analysis with the indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin (cytosolic proteins) or Lamin B (nuclear proteins). Data are shown as means ± s.e. *P < 0.05, and **P < 0.01 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Alb: 11657
Cre: 2777477
NBR1: 17966
Nrf2: 18024"
  },
  {
    "caption": "(B) Real-time PCR. Total RNAs were prepared from primary hepatocytes described in (A). Values were normalized against the amount of mRNA in the Nrf2f/f hepatocytes expressing GFP. The experiments were performed at least three times. Data are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Nrf2: 18024"
  },
  {
    "caption": "(C) Immunofluorescence microscopy. Hepatocytes isolated from Nrf2f/f and Nrf2f/f; Alb-Cre mice were infected with LacZ or NBR1 adenovirus for 48 hrs and then immunostained with anti-p62 and anti-NBR1 antibodies. Each inset is a magnified image. Bars: 20 µm. The number and size of p62-bodies were measured in more than 100 cells. Data are shown as means ± s.e. ***P < 0.001 as determined by Welch's t-test.",
    "ncbi_link": "LacZ: 
Alb: 11657
Cre: 2777477
NBR1: 17966
Nrf2: 18024"
  },
  {
    "caption": "(B) Fluorescence microscopy. p62-deficient MEFs were co-transfected with mCherry-GFP-p62 in combination with wild-type NBR1 or NBR1 D50R mutant. 48 hrs after the transfection, fluorescence images were observed. Bars: 10 µm. The number of puncta positive for only red-signal in each MEFs was counted in more than 100 cells. Bar graphs are represented as means ± s.e. ***P < 0.001 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
mCherry: 
NBR1: 17966
p62: 18412"
  },
  {
    "caption": "(A) Immunoblot analysis. Primary hepatocytes were isolated from wild-type (wt), p62f/f; Alb-Cre (p62KO) and Nrf2f/f; Alb-Cre (Nrf2KO) mice. The hepatocytes were challenged with 10 μM sodium arsenite [As (III)] for 12 hrs. Cell lysates were prepared and subjected to immunoblot analysis with anti-NBR1 and anti-Actin antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin. Data are shown as means ± s.e. *P < 0.05, and **P < 0.01 as determined by Welch's t-test.",
    "ncbi_link": "Alb: 11657
Cre: 2777477
Nrf2: 4780
p62: 18412"
  },
  {
    "caption": "A) Immunoblot analysis. Primary hepatocytes were isolated from Nbr1f/f mice and then infected with adenovirus GFP or Cre for 48 hrs. Thereafter, the hepatocytes were divided into 3 groups: 1. Cultured in regular medium (-), 2. Treated with 10 μM As (III) for 12 hr [As (III)] and 3. After treated with 10 μM As (III) for 12 hr, cultured in regular medium for another 12 hr (Wash). Cell lysates were prepared and subjected to immunoblot analysis with indicated antibodies. Data shown are representative of three separate experiments. Bar graphs indicate the quantitative densitometric analysis of the indicated proteins relative to actin. Data are shown as means ± s.e. *P < 0.05, **P < 0.01, and ***P < 0.001 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Cre: 2777477
Nbr1: 17966"
  },
  {
    "caption": "B) Real-time PCR. Total RNAs were prepared from primary hepatocytes described in (A). Values were normalized against the amount of mRNA in the Nbr1f/f hepatocytes expressing GFP under normal culture conditions. The experiments were performed at least three times. Data are shown as means ± s.e. *P < 0.05 as determined by Welch's t-test.",
    "ncbi_link": "GFP: 
Nbr1: 17966"
  },
  {
    "caption": "(C) Immunofluorescence microscopy. Nbr1f/f hepatocytes were infected with LacZ or Cre adenovirus for 48 hrs and, when indicated, challenged with 10 μM As (III) for 12 hrs. The cells were then immunostained with anti-p62 and anti-NBR1 antibodies. Each inset is a magnified image. Bars: 20 µm. The number and size of p62-bodies were measured in more than 100 cells. Data are shown as means ± s.e. **P < 0.01, and ***P < 0.001 as determined by Welch's t-test. (D) Role of NBR1 in the p62-liquid droplets and the p62-mediated Nrf2 activation. Oxidative stress up-regulates the level of NBR1, which enhances the phosphorylation and liquid-droplet formation of p62. The resulting p62-droplets are resistant to autophagic degradation and serve as signaling nodes for the activation of Nrf2. Since p62 is one of the targets of Nrf2, increased level of p62 in cooperation with NBR1 promote the formation of liquid droplets and contributes to the persistent activation of Nrf2 against oxidative stress. ",
    "ncbi_link": "LacZ: 
Cre: 2777477
Nbr1: 17966"
  },
  {
    "caption": "A) Family pedigree with SEC16B homozygosity in the patient and heterozygosity in the mother and one brother. B) Validation of the SEC16B mutation by Sanger sequencing. Sanger sequencing of gDNA of the patient, brother, mother and healthy control. Magnification of the electropherogram shows the position c.424 and the base change CT.",
    "ncbi_link": "SEC16B: 89866"
  },
  {
    "caption": "C-F) C) COL1A1 and COL1A2 expression in the ER of SEC16B patient and control fibroblasts assessed by western blotting. KDEL, Calnexin, BIP and PDI, all ER-resident proteins were used as ER markers. E) Golgi complex was isolated according to the method described in Current Protocols in Cell Biology, Unit 3.9 from healthy control cells and patient derived fibroblasts. Subsequently, COL1A1 and COL1A2 expression in the Golgi complex of SEC16B patient and control fibroblasts were determined by western blotting. GM130 (Golgi-resident protein) was used as marker for Golgi complex. All cells were treated with ascorbic acid 0.05 mg/ml for 20 hours before the Golgi complex was isolated. D, F) Quantification of the bands that was done with Bio-Rad Image Lab 6.1 software to calculate the expression levels. COL1A1 and COL1A2 band intensities were either normalized to (D) calnexin or (F) GM130. The normalized intensities were reported as fold change patient to control cells. Columns represent the mean of three (D) or two (F) independent experiments (raw values: 0.27 and 0.53 for COL1A1 and 0.29, 0.21 for COL1A2) respectively. Biological replicates were performed; bars, standard error of the mean (SEM); *significant (p < 0.05) differences obtained by using unpaired two-tailed t test",
    "ncbi_link": "SEC16B: 89866"
  },
  {
    "caption": "A) Micrograph of thin-section electron microscopy for fibroblasts from SEC16B mutant patient cells and healthy control cells. Arrows point to rER, arrowheads to MVBs/MLBs, star indicates autophagosome. Scale bar is 1 µm. Summary of the number of the autophagosomes.",
    "ncbi_link": "SEC16B: 89866"
  },
  {
    "caption": "Patient cells were either transfected with pCDNA3 empty vector (empty vector) or pcDNA3 which encodes wt SEC16B (TF). Cells were then selected with puromycin and single colonies were picked up and expanded. Established single colonies were used. B) Immunofluorescence labeling of the control and the patient fibroblasts for COL1A1 marker proα1 (I) and rough ER marker KDEL. The staining showed that while COL1A1 is accumulated in the ER of patient cells transfected with empty vector, it is not accumulated in the ER of the patient cells transfected with SEC16B wt. Scale bar is 25 µm",
    "ncbi_link": "SEC16B: 89866"
  },
  {
    "caption": "Patient cells were either transfected with pCDNA3 empty vector (empty vector) or pcDNA3 which encodes wt SEC16B (TF). Cells were then selected with puromycin and single colonies were picked up and expanded. Established single colonies were used. D) LC3B showed reduced expression in the TF SEC16B mutant cells (similar to expression in healthy control Fig. 5B) when compared to empty vector transfected patient cells. E) Quantification of the bands. All band intensities were normalized to those of Actin and reported as fold change patient to control cells. Columns represent the mean of three independent experiments, biological replicates were performed; bars, standard error of the mean (SEM); **highly significant (p < 0.001 differences obtained by using unpaired two tailed t-test.",
    "ncbi_link": "SEC16B: 89866"
  },
  {
    "caption": "A) HeLa cells were transfected with plasmids encoding GFP-tagged SEC16B-R142W. After 24 hours, cells were fixed and immunostained against SEC13 to label ERES. Green color shows SEC16B-R142W expression, red colors shows SEC13 expression and yellow color shows the overlap of the two colors. The scale bars are 10 µm.",
    "ncbi_link": "GFP: 
SEC16B: 89866"
  },
  {
    "caption": "D) HepG2 cells were transfected with the indicated siRNA. After 48h, cells were transfected with plasmids encoding signal sequence GFP (ssGFP) as part of a RUSH construct. After 24 hours, cells were treated with 40 mM biotin for 15 minutes followed by fixation and immunostaining for GM130 to label the Golgi complex. The scale bars are 10 µm.",
    "ncbi_link": "signal sequence GFP: 
ssGFP: "
  },
  {
    "caption": "A: Immunoblot analysis of wild type (WT), FAM83D-/- knockout (KO) and FAM83DGFP/GFP knockin (KI) U2OS cell lines. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
FAM83D: 81610"
  },
  {
    "caption": "A: STLC-synchronised mitotic (M) wild-type (WT), FAM83D-/- knockout (KO) and FAM83DGFP/GFP knockin (KI) U2OS cells were subjected to anti-CK1α immunofluorescence and GFP fluorescence microscopy. DNA is stained with DAPI. Scale bars, 20 µm.",
    "ncbi_link": "GFP: 
FAM83D: 81610"
  },
  {
    "caption": "B: STLC-synchronised mitotic (M) FAM83D-/- knockout (KO), FAM83DGFP/GFP knockin (KI) and FAM83DGFP/GFP(F283A) knockin (FA) U2OS cells were subjected to anti-CK1α immunofluorescence and GFP fluorescence microscopy. DNA is stained with DAPI. Scale bars, 20 µ",
    "ncbi_link": "GFP: 
FAM83D: 81610"
  },
  {
    "caption": "F: KI cells were infected with retroviruses encoding either VHL, aGFP.16, or VHL-aGFP.16. Uninfected cells were used as a control. Cells were lysed and subjected to IB with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
VHL: 7428"
  },
  {
    "caption": "B: FAM83D-/- (KO), wild-type (WT), and two independent clones from a CRISPR/Cas9-mediated knockin rescue of FAM83D cDNA into FAM83D-/- cells (c. 6 and c. 11), were synchronized in mitosis (M) with STLC. Asynchronous (AS) cells were included as a control. Cells were lysed and subjected to immunoblotting (IB) with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "CRISPR: 
FAM83D: 81610
Cas9: 901176"
  },
  {
    "caption": "G: Asynchronous (AS) FAM83DGFP/GFP/ mCherry/mCherryCSNK1A1 knockin U2OS cells were fixed and imaged. Representative images from the indicated cell cycle stages are included. Scale bars, 10 µm.",
    "ncbi_link": "GFP: 
mCherry: 
CSNK1A1: 1452
FAM83D: 81610"
  },
  {
    "caption": "A: Nocodazole-synchronised mitotic FAM83DGFP/GFP knockin U2OS cells were lysed and subjected to GFP TRAP immunoprecipitation (IP), followed by incubation ± λ-phosphatase. Asynchronous (AS) cells were used as a control. Whole cell extracts (input) and IP samples were subjected to SDS-PAGE and subsequent immunoblotting (IB) with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
FAM83D: 81610"
  },
  {
    "caption": "F: STLC-synchronised mitotic wild-type U2OS cells were subjected to qRT-PCR analysis using primers for FAM83D, HMMR, CSNK1A1, and CCNB1. AS cells were used as a control. Error bars, SEM; *, P<0.01; Student's T-test. n=3",
    "ncbi_link": "CCNB1: 891
CSNK1A1: 1452
FAM83D: 81610
HMMR: 3161"
  },
  {
    "caption": "H: STLC-synchronised mitotic wild-type (WT) and HMMR knockout (KO) mouse embryonic fibroblasts (MEFs) were lysed and subjected to IB with the indicated antibodies. AS cells were included as a control. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "HMMR: 15366"
  },
  {
    "caption": "B: STLC-synchronised mitotic FAM83DGFP/GFP knockin (KI), FAM83DGFP/GFP (F283A) (FA), and FAM83DGFP/GFP(F283A) stably expressing aGFP.16-CK1α (FA + aGFP.16-CK1α) U2OS cells were subjected to GFP TRAP immunoprecipitation (IP), followed by immunoblotting (IB) with the indicated antibodies. Asynchronous (AS) cells were used as controls. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
CK1α: 1452
FAM83D: 81610"
  },
  {
    "caption": "C: FA cells were infected with retroviruses encoding wild-type aGFP.16-CK1α (WT), or aGFP.16-CK1α with one of two distinct CK1α kinase-inactive mutants (D136N or K46D). Uninfected cells (-) were included as a control. Cells were lysed, subjected to anti-GFP IP and IB with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
CK1α: 1452"
  },
  {
    "caption": "F: FAM83D-/- knockout (KO), KI, and FA cells were synchronised in mitosis (M) using STLC. Lysed extracts were subjected to anti-GFP IPs, followed by ATP [γ-32P] kinase assays, using an optimised CK1 substrate peptide (CK1tide). AS cells were used as controls. Error bars, SEM; P<0.01; ANOVA. n=3. Input and IP samples were analysed by IB with the indicated antibodies. Data information: All blots are representative of at least 3 independent experiments.",
    "ncbi_link": "FAM83D: 81610"
  },
  {
    "caption": "B. Carfilzomib, Bortezomib and MLN9708 activate  luciferase activity in   M2  macrophages  derived from  Il-1β-luciferase transgenic  mice. BMDMs from  IL-1β-luciferase transgenic mice were treated by  IL-4  (20 ng/mL) for 24 hours to differentiate into mature M2  macrophages, and then used for screening of FDA compounds (5 μM). The X axis stands for the code of the drug.",
    "ncbi_link": "luciferase: 
Il-1β: 16176
IL-1β: 16176"
  },
  {
    "caption": "F, G. Carfilzomib, Bortezomib  and  MLN9708 promote the mRNA  expression of  Il-1β in M2 macrophages. BMDMs (F) or Raw264.7 cells (G) were pretreated by  IL-4 (20 ng/mL) for 24 hours, then treated by DMSO, Carfilzomib (1 μM), Bortezomib (1 μM), or MLN9708 (2 μM). RNA was extracted from  BMDMs or Raw264.7 cells 6 hours after stimulation and the expression  of Il-1β were quantified through  RT-qPCR. Data from three experiments are presented as the mean ± SD. T test was used for statistical analysis of differences between groups. ***p < 0.001 (student's t-test). H, I. Carfilzomib, Bortezomib and MLN9708 promote the secretion of inflammatory cytokine  IL-1β  in  M2 macrophages. BMDMs  (H) or Raw264.7 cells (I) were pretreated by IL-4 (20 ng/mL) for 24 hours, then stimulated by DMSO, Carfilzomib (500 nM), Bortezomib (500 nM) or MLN9708 (500 nM). Secretion of IL-1β were measured through  ELISA 24 hours later. Data from three experiments are presented as the mean ± SD. T test was used for statistical analysis of differences between groups. **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Il-1β: 16176"
  },
  {
    "caption": "A. The most effective one among the candidate compounds,  Carfilzomib, significantly promotes the  expression of M1 macrophage markers, as well as reduces the expression of M2 macrophage  markers. BMDMs were pretreated by IL-4  (20 ng/mL) for 24 hours, then stimulated by DMSO or Carfilzomib (1 μM). RNA was extracted from cells 6 hours after stimulation and the  expression of M1 (Il-6/Inos) or  M2 (Cd206/Arg1)  macrophage markers were quantified through  RT-qPCR. Data from three experiments are presented as the mean ± SD. T test was used for statistical analysis of differences between groups. ***p < 0.001 (student's t-test).",
    "ncbi_link": "Arg1: 11846
Il-6: 16193
Inos: 106736473
Cd206: 17533"
  },
  {
    "caption": "E. Carfilzomib promotes the  phagocytosis  of macrophages. BMDMs  were pretreated by IL-4 (20 ng/mL) for 24 hours, then stimulated by  DMSO or Carfilzomib (500 nM) for 12 hours. After starving for 2 hours and  stained  with Red membrane dye, BMDMs (red) were incubated with  L1210-GFP cells (green) in serum-free medium for another 2 hours. Phagocytosis effect was observed and photographed under fluorescence microscope. Scale bars, 50 μm (up), 20 μm (down). The yellow arrows indicated L1210 that is phagocytosed by macrophages. F. Statistics represent the  number of phagocytosis L1210 in 100  macrophages. Data are means ± SD of three independent experiments. **p < 0.01 (student's t-test).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "M. Carfilzomib  promotes the M1-polarization of Tumor associated macrophages  in vitro. BMDMs  were cultured with tumor culture supernatant (TSN) produced by L1210 cells, followed by activation with DMSO or Carfilzomib  (1 μM). RNA was extracted from cells and the expression of  Il-1β, Il-6, Inos were quantified through  RT-qPCR  6 hours after stimulation. The data are means ± SD of three independent experiments. **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Il-1β: 16176
Il-6: 16193
Inos: 106736473"
  },
  {
    "caption": "A, B. Carfilzomib  and proteasome inhibitor MG132 activate Il-1β luciferase in macrophages. (A) BMDMs were treated with   IL-4 (20 ng/mL) for 24 hours and then stimulated by DMSO, Carfilzomib  (1 μM), or MG132  (5 μM). (B) BMDMs were stimulated by DMSO, Carfilzomib (1 μM) or MG132  (5 μM)) for 1 hour, then induced with  IL-4 (20 ng/mL). Luciferase assays were monitored 12 hours after stimulation. The data are means ± SD of three independent experiments. ***p < 0.001 (student's t-test).",
    "ncbi_link": "luciferase: 
Il-1β: 16176"
  },
  {
    "caption": "E. Carfilzomib, Bortezomib, MLN9708 and MG132 induce ER stress response. BMDMs were pretreated with  IL-4 (20 ng/mL) for 24 hours and then stimulated by  DMSO or  Carfilzomib (1 μM),  Bortezomib  (1 μM), MLN9708  (2 μM), MG132 (5 μM). RNA was extracted from cells 3 hours or 6 hours after stimulation and the expression of ER  stress related genes (Bip, Chop) were detected through  RT-qPCR. The data are means ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Chop: 13198
Bip: 14828"
  },
  {
    "caption": "G. Inhibition of  ER stress impairs the ability of  Carfilzomib, Bortezomib,  MLN9708 and MG132 to reprogram  M2 towards M1-like macrophages. BMDMs were induced by  IL-4 (20 ng/mL) for 24 hours, then pretreated with  4-PBA (5 mM) for 1 hour and stimulated by Carfilzomib  (1μM), Bortezomib (1μM), MLN9708 (2 μM), MG132 (5 μM). RNA was extracted from cells 6 hours after stimulation and the expression of Il-1β,  Il-6 and  Inos were detected through RT-qPCR. The data are means ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Il-1β: 16176
Il-6: 16193
Inos: 106736473"
  },
  {
    "caption": "A, B Deficiency of  Ern1 reduces the expression  of inflammatory related genes. Wild-type and Ern1-/- Raw264.7 cells (A) or BMDMs (B) were pretreated by IL-4  (20 ng/mL) for 24 hours, then stimulated by  DMSO or Carfilzomib  (1 μM). The mRNA of Il-1β and Il-6  were quantified through  RT-qPCR 6 hours after stimulation. The data are means ± SD of three independent experiments. **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Ern1: 78943
Il-1β: 16176
Il-6: 16193"
  },
  {
    "caption": "E.  Kira6 inhibits the  expression of ER  stress related genes and inflammatory related genes.  BMDMs  was treated by IL-4 (20 ng/mL) for 24 hours, treated with  Kira6  (100 nM) for 1 hour, and then stimulated by  Carfilzomib (1 μM) for 6 hours. RNA was extracted from cells and the expression  of  Bip, Chop,  Il-1β and  Il-6  were quantified through  RT-qPCR. The data are means ± SD of three independent experiments. *p < 0.05, **p < 0.01 (student's t-test). F, G. Carfilzomib has no effect on splicing of XBP1  in M2 macrophages. BMDMs (F) or Raw264.7  cells (G) were pretreated by IL-4 (20 ng/mL) for 24 hours, then stimulated with DMSO, Carfilzomib (1 μM) or TUN  (500 nM). The mRNA expression of sXBP1 and unXBP1 were detected through  RT-qPCR 6 hours after stimulation. The data are means ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Chop: 13198
Bip: 14828
Il-1β: 16176
Il-6: 16193
XBP1: 22433"
  },
  {
    "caption": "L. Carfilzomib activates NF-κB signaling pathway through IRE1α in M2 macrophages. Wild-type and Ern1-/- Raw264.7 cells were pretreated by  IL-4 (20 ng/mL) for 24 hours, then stimulated by  Carfilzomib  (1 μM) for indicated time points. WCL were analyzed by IB  with indicated antibodies.",
    "ncbi_link": "Ern1: 78943"
  },
  {
    "caption": "K, L. Carfilzomib shrinks tumor through modulating tumor microenvironment. EG7 cells were inoculated in wild-type or  LyzM-cre;lsl-dTA to allow tumor xenograft  to reach a volume of around 80 mm3. Mice were randomized for treatment (n=5) by saline or Carfilzomib  for two weeks. The  xenografts were dissected to photograph (K) or weigh (L) after treatment. Data are shown as mean ±SD and n indicates the number of biological replicates. *p < 0.05, ***p < 0.001 (student's t-test).",
    "ncbi_link": "dTA: 
cre: 2777477
LyzM: 17105"
  },
  {
    "caption": "A. Carfilzomib, Bortezomib and MLN9708 promote the  expression of M1  macrophage markers (Il-1β,  Il-6,  Tnfα) and reduce the expression  of M2 macrophage  markers (Il-10, Tgfβ) in  macrophages  derived from PBMCs. After induced by  IL-4 (20 ng/ml) for 24 hours to differentiate into mature M2 macrophages,  PBMCs derived macrophages  were stimulated by Carfilzomib  (1 μM), Bortezomib (1 μM) or MLN9708 (2 μM). RNA was extracted from cells 6 hours after stimulation and the expression of mRNA were quantified through RT-qPCR. Data from three experiments are presented as the mean ± SD. T test was used for statistical analysis of differences between groups. *p < 0.05, **p < 0.01, ***p < 0.001 (student's t-test).",
    "ncbi_link": "Il-10: 3586
Il-1β: 3553
Il-6: 3569
Tgfβ: 7040
Tnfα: 7124"
  },
  {
    "caption": "(C) Representative FACS plot showing loss of hCD2 marker expression of Ch14 ICL MEFs after treatment with 4-hydroxy tamoxifen (4OHT) for 14 days to induce Cre, compared to Ethanol treated control cells (See also Appendix figure S1A).",
    "ncbi_link": "Ch14: "
  },
  {
    "caption": "(B) Tumor growth curve after early passage ICL cells were injected into flanks of athymic nude mice (n = 5 per group and error bars denote SEM, p<0.05 for Ch9 and Ch14).",
    "ncbi_link": "Ch14: 
Ch9: "
  },
  {
    "caption": "Representative karyotypes of late passage, large T antigen immortalized MEFs after exposure to Cre recombinase and serially sorted for control (hCD2 plus) and ICL (hCD2 Minus) cells for chromosome lines (A) Ch12 Boxed panels denote targeted chromosome loss; arrows and asterisks denote shared and unshared, non-targeted chromosomal copy number variations respectively.",
    "ncbi_link": "Ch12: "
  },
  {
    "caption": "Representative karyotypes of late passage, large T antigen immortalized MEFs after exposure to Cre recombinase and serially sorted for control (hCD2 plus) and ICL (hCD2 Minus) cells for chromosome lines (B) Ch14. Boxed panels denote targeted chromosome loss; arrows and asterisks denote shared and unshared, non-targeted chromosomal copy number variations respectively.",
    "ncbi_link": "Ch14: "
  },
  {
    "caption": "Representative karyotypes of late passage, large T antigen immortalized MEFs after exposure to Cre recombinase and serially sorted for control (hCD2 plus) and ICL (hCD2 Minus) cells for chromosome lines (C) Ch9 Boxed panels denote targeted chromosome loss; arrows and asterisks denote shared and unshared, non-targeted chromosomal copy number variations respectively.",
    "ncbi_link": "Ch9: "
  },
  {
    "caption": "Representative karyotypes of late passage, large T antigen immortalized MEFs after exposure to Cre recombinase and serially sorted for control (hCD2 plus) and ICL (hCD2 Minus) cells for chromosome lines (D) Ch10. Boxed panels denote targeted chromosome loss; arrows and asterisks denote shared and unshared, non-targeted chromosomal copy number variations respectively.",
    "ncbi_link": "Ch10: "
  },
  {
    "caption": "Karyotypic analysis of later passage, control and ICL of a replicate (#1) of Ch12 (A). All chromosomes are shown for 20 metaphases. Target chromosomes are boxed in red.",
    "ncbi_link": "Ch12: "
  },
  {
    "caption": "Karyotypic analysis of later passage, control and ICL of a replicate (#1) of Ch10 (B) All chromosomes are shown for 20 metaphases. Target chromosomes are boxed in red.",
    "ncbi_link": "Ch10: "
  },
  {
    "caption": "Karyotypic analysis of later passage, control and ICL of a replicate (#1) of Ch14 (C) All chromosomes are shown for 20 metaphases. Target chromosomes are boxed in red.",
    "ncbi_link": "Ch14: "
  },
  {
    "caption": "Karyotypic analysis of later passage, control and ICL of a replicate (#1) of Ch9 (D) lines. All chromosomes are shown for 20 metaphases. Target chromosomes are boxed in red.",
    "ncbi_link": "Ch9: "
  },
  {
    "caption": "(A) Tumor growth curve after later passage ICL cells were injected into flanks of athymic nude mice (n = 5 per group and error bars denote SD, p<0.0005 for Ch9, p<0.05 for Ch10 and p<0.005 for Ch14).",
    "ncbi_link": "Ch10: 
Ch14: 
Ch9: "
  },
  {
    "caption": "(C) Tumor growth curve after later passage ICL cells were injected into flanks of NOD/SCID mice (n = 5 per group and error bars denote SD p<0.0005 for Ch10 and p<0.005 for Ch14).",
    "ncbi_link": "Ch10: 
Ch14: 
NOD: 
SCID: "
  },
  {
    "caption": "(A) Growth curve of the later passage ICL lines Ch10 and Ch14 under adherent in vitro culture conditions (n=3 for each data set and error bars denote SD, p<0.005 for Ch10 and p<0.0001 for Ch14). (See also Appendix Figure S3A)",
    "ncbi_link": "Ch10: 
Ch14: "
  },
  {
    "caption": "(B) Colony formation in ICL and control MEFs. 5000 cells were seeded in 10 cm plates and stained with Methylene blue after three days. Representative colony formation images in Ch10 and Ch14 are shown (left) and quantification of colonies formed (right) in the 4 ICL lines (n=3 for each data set and error bars denote SD, p<0.005 for Ch10, Ch12 and Ch14 and ns for Ch9).",
    "ncbi_link": "Ch10: 
Ch12: 
Ch14: 
Ch9: "
  },
  {
    "caption": "(C) Quantification of growth in ultra-low adherent, sphere forming conditions for the 4 ICL lines (n=3 for Ch10 and Ch14, n=6 for Ch9 and Ch12 and error bars denote SD, p<0.0001 for Ch9, p<0.001 for Ch10 and p<0.05 for Ch12 and Ch14).",
    "ncbi_link": "Ch10: 
Ch12: 
Ch14: 
Ch9: "
  },
  {
    "caption": "(A) Flow cytometry analysis of tail blood from Ch10/+ (control) at 30 days post tamoxifen administration, Ch10/+; Id1 Cre/+ at 30 days post tamoxifen administration, and Ch10/+; Id1Cre/+ at 80 days post tamoxifen administration.",
    "ncbi_link": "Ch10: 
Id1: 15901"
  },
  {
    "caption": "(B) Determination of number of γH2AX foci in ICL and control nuclei and quantification (scale bars denote 10μm, p<0.0001 for Ch9, Ch10 and Ch12, p<0.05 for Ch14; n=25 for each dataset and error bars denote SD). (See also Figures S5A and S5B)",
    "ncbi_link": "Ch10: 
Ch12: 
Ch14: 
Ch9: "
  },
  {
    "caption": "(C) Number of γH2AX positive cells in formalin fixed ICL and control tumor sections by immunofluorescence staining and quantification (Scale bars denote 20μm, p<0.0001 for Ch10 and p<0.05 for Ch14).",
    "ncbi_link": "Ch10: 
Ch14: "
  },
  {
    "caption": "(B) Total lysates from LN229 cells in which Merlin was or was not knocked out (KO) were subjected to western blotting.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(E) LN229 cells transduced with a Merlin or scrambled shRNA were treated with DMSO, ionomycin (Iono) or thapsigargin (TG). Total lysates of these cells were subjected to western blotting. The major Merlin band is indicated by an asterisk. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot. Ubiquitinated Merlin is marked with an arrow.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(G) LN229 cells stably transduced with 6x-Histidine-tagged ubiquitin (His-Ubi) were treated with DMSO or thapsigargin (TG). These cells were lysed and subjected to nickel-charged affinity purification followed by western blotting for endogenous Merlin. Both arrowhead and arrow point to the mono-ubiquitinated Merlin. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Ubi: 850620
ubiquitin: 850620"
  },
  {
    "caption": "(H) LN229 cells stably transduced with 6x-Histidine-tagged ubiquitin (His-Ubi) were detached or reseeded as in (C). These cells were lysed and subjected to nickel-charged affinity purification followed by western blotting for endogenous Merlin. Arrowheads and arrows point to the mono- or di-ubiquitinated Merlin (see a longer exposed blotting results in Figure EV1D). The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Ubi: 850620
ubiquitin: 850620"
  },
  {
    "caption": "LN229 cells transduced with vector or EGFP-RAC1(Q61L) (D) were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "EGFP: 
RAC1: 5879"
  },
  {
    "caption": "(E) LN229 cells transduced with vector or Myc-PAK1(T423E) (E) were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Myc: 
PAK1: 5058"
  },
  {
    "caption": "(F) LN229 cells stably transduced with wild-type Merlin or the indicated mutants were treated with DMSO or thapsigargin (TG) and analyzed by western blot. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot. Native Merlin (asterisk); ubiquitinated Merlin (arrow).",
    "ncbi_link": "Merlin: 18016"
  },
  {
    "caption": "(G) Merlin-depleted LN229 cells stably transduced with Flag-tagged wild-type Merlin or the indicated mutants were treated with DMSO or thapsigargin (TG). The cells were lysed and subjected to immunoprecipitation with a Flag antibody. The lysate and immunoprecipitated products were subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Flag: 
Merlin: 4771"
  },
  {
    "caption": "(B) LN229 cells transduced with a pool of four siRNAs against NEDD4L (+) or a scrambled siRNA (-) were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane of the short exposure blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(C) LN229 cells stably transduced with indicated shRNAs targeting NEDD4L or a scrambled shRNA were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(D) LN229 cells stably transduced with indicated shRNAs targeting NEDD4L or a scrambled shRNA were detached by trypsinization (see Methods) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(E) LN229 cells stably transduced with 6x-Histidine-tagged Ubiquitin (His-Ubi) were then stably transduced with indicated shRNAs targeting NEDD4L or a scrambled shRNA. These cells were detached as in (D), lysed and subjected to nickel-charged affinity purification followed by western blotting for endogenous Merlin. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "NEDD4L: 23327
Ubi: 850620
Ubiquitin: 850620"
  },
  {
    "caption": "(A) LN229 cells transduced with a pool of four siRNAs against AMOTL1 (+) or a scrambled siRNA (-) were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "AMOTL1: 154810"
  },
  {
    "caption": "(B) LN229 cells stably transduced with 6x-Histidine-tagged Ubiquitin (His-Ubi) were then stably transduced with indicated shRNAs against AMOTL1 or a scrambled shRNA control (sh-Co.). These cells were detached, lysed and subjected to nickel-charged affinity purification followed by western blotting for endogenous Merlin. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "AMOTL1: 154810
Ubi: 850620
Ubiquitin: 850620"
  },
  {
    "caption": "(D) Merlin-depleted LN229 cells stably expressing Flag-HA-tagged Merlin were transduced with scrambled shRNA (sh-Co.) or two distinct shRNAs targeting AMOTL1, treated with DMSO or thapsigargin (TG) and subjected to Flag immunoprecipitation followed by western blotting.",
    "ncbi_link": "AMOTL1: 154810"
  },
  {
    "caption": "(F) Merlin-depleted LN229 cells stably transduced with Flag-tagged wild-type Merlin or the indicated mutants were treated with DMSO or thapsigargin (TG). The cells were lysed and subjected to immunoprecipitation with a Flag antibody. The lysate and immunoprecipitated products were subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Flag: 
Merlin: 4771
Merlin: 18016"
  },
  {
    "caption": "(A) LN229 cells stably transduced with Flag-tagged wild-type Merlin or the S518D mutant were treated with thapsigargin and subjected to immunoprecipitation with a Flag antibody and followed by SDS-PAGE. Outlined gel pieces were analyzed by mass spectrometry. (B) Numbers of unique peptides of Merlin or Ubiquitin from each outlined gel pieces in (A) are shown. ",
    "ncbi_link": "Flag: 
Merlin: 4771"
  },
  {
    "caption": "(F) Merlin-depleted LN229 cells expressing His-Ubiquitin were stably transduced with the indicated HA-tagged Merlin forms or an empty vector. These cells treated with DMSO or thapsigargin were subjected to nickel affinity purification in a denaturing step followed by western blotting for HA. Arrows indicate mono-ubiquitinated Merlin. The red asterisk indicates native Merlin and black asterisks indicate non-specific signals. The ratio of mono-ubiquitinated to native Merlin in each lane of the input blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "HA: 
Merlin: 4771
Ubiquitin: 850620"
  },
  {
    "caption": "(G) Merlin-depleted LN229 cells were stably transduced with an empty vector, Flag-tagged wild-type (WT) Merlin or its K396R mutant. These cells were detached (S, suspension) by trypsinization using the procedure described in the Methods section and reseeded (A, attached) for two hours. Cell lysates were subjected to immunoprecipitation with a Flag antibody followed by western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane of the lysate blot was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Flag: 
Merlin: 4771"
  },
  {
    "caption": "(H) Merlin-depleted LN229 cells stably transduced with wild-type (WT) Merlin or its K396R mutant were treated with DMSO or thapsigargin (TG) and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(I) Merlin-depleted LN229 cells stably transduced with HA-tagged wild-type (WT) Merlin or its K396R mutant were treated as described in (G) and subjected to western blotting. The ratio of mono-ubiquitinated to native null in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "HA: 
Merlin: 4771"
  },
  {
    "caption": "(B) Merlin-depleted LN229 cells were reconstituted with wild type (WT) Merlin or its mutants, treated with DMSO or thapsigargin (TG), and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(C) Merlin-depleted LN229 cells were reconstituted with wild type (WT) Merlin or its mutants, treated with DMSO or thapsigargin (TG), and subjected to western blotting. The ratio of mono-ubiquitinated to native Merlin in each lane was quantified by Image J and is shown under the blot.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(D) LN229 cells transfected with a pool of four siRNAs targeting NEDD4L (+) or a scrambled siRNA (-) were treated with DMSO or thapsigargin (TG) and subjected to western blotting.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(E) Merlin-depleted LN229 cells were stably transduced with empty vector, Flag-tagged wild-type (WT) Merlin, or its K396R mutant. These cells were detached (S, suspension) by trypsinization using the procedure described in Methods and reseeded (A, attached) for two hours. Cell lysates were subjected to western blotting.",
    "ncbi_link": "Flag: 
Merlin: 4771"
  },
  {
    "caption": "(F) LN229 cells transfected with a pool of four siRNAs targeting NEDD4L (+) or a scrambled siRNA (-) were detached (Susp., suspension) by trypsinization using the procedure described in Methods and reseeded (Attach, attached) for two hours. Total lysates from these cells were subjected to western blotting.",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(G) LN229 cells transfected with indicated siRNAs were seeded for 3 hours. CTGF or CYR61 mRNA in these cells was quantified by q-RT-PCR. *P<0.05, **P<0.01, ****P<0.0001. Mean±s.e.m, N=4 biological repeats, unpaired t-test.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490"
  },
  {
    "caption": "(A) LN229 cells stably transduced withHA-Lats1 (two leftmost panels) or vector only (right panel) were treated with DMSO or thapsigargin (TG) and subjected to PLA using HA and Merlin antibodies. Scale bar = 10 μm. (B) PLA signals (dots) in each cell from the results in (A) were quantified. Mean±s.e.m, two-way ANOVA. *P<0.05, ***P<0.001, ****P<0.0001. Each data point represents an image field containing an average of 10 cells. N=4-9 images for each condition as indicated. All images were collected from one experiment. Two independent experiments were performed and gave similar results. ",
    "ncbi_link": "HA: 
Lats1: 9113"
  },
  {
    "caption": "(C) Merlin-depleted LN229 cells were stably transduced with HA-tagged wild-type (WT) Merlin or its mutants. These cells were treated with thapsigargin (TG) for 15 minutes and subjected to PLA using HA and Lats1 antibodies. Scale bar = 20 μm. (D) PLA signals (dots) in each cell from the results in (C) were quantified. Mean±s.e.m, Ordinary one-way ANOVA. ****P<0.0001. Each data point represents an image field containing an average of 10 cells. NVector=8, NWT=16, NK396R=18, NK159R=17 images. All images were collected from one experiment. Two independent experiments were performed and gave similar results. ",
    "ncbi_link": "HA: 
Merlin: 4771"
  },
  {
    "caption": "(E) Merlin-depleted LN229 cells stably transduced with empty vector, Flag-tagged wild-type (WT) Merlin, or its K396R mutant were subjected to immunoprecipitation with a Flag antibody followed by western blotting.",
    "ncbi_link": "Flag: 
Merlin: 4771"
  },
  {
    "caption": "(G) Merlin-depleted LN229 cells were stably transduced by HA-tagged Merlin. These cells were then transduced with a pool of four siRNAs against NEDD4L or a scrambled control siRNA and treated with DMSO or thapsigargin (TG). PLA was performed in these cells using HA and Lats1 antibodies, and the PLA signals (dots, showed in Figure EV5E) in each cell were quantified. Mean±s.e.m, two-way ANOVA. ****P<0.0001. Each data point represents an image field containing averagely 10 cells. N=12 images in all conditions, except for Nsi-Control:TG=13 images. All images were collected from one experiment. Two independent experiments were performed and showed similar results.",
    "ncbi_link": "HA: 
NEDD4L: 23327
Merlin: 4771"
  },
  {
    "caption": "(A) Met5-A cells stably transduced with the indicated shRNAs targeting Merlin or a scrambled shRNA were subjected to the BrdU incorporation assay. Scale bar = 40 μm. (B) The percentage of BrdU positive cells from (A) was quantified. Mean±s.e.m, N=3 biological repeats, paired t-test. **P<0.01, ***P<0.001.",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(C) Met5-A cells stably transduced with the indicated shRNAs targeting NEDD4L or a scrambled shRNA were subjected to the BrdU incorporation assay. Scale bar = 40 μm. (D) The percentage of BrdU positive cells from (C) was quantified. Mean±s.e.m, N=3 biological repeats, paired t-test. **P<0.01, ***P<0.001. ",
    "ncbi_link": "NEDD4L: 23327"
  },
  {
    "caption": "(E) Meso-33 cells transduced with vector or the indicated Merlin forms were subjected to the BrdU incorporation assay. Scale bar = 40 μm. (F) The percentage of BrdU positive cells from (E) was quantified. Mean±s.e.m, N=3 biological repeats, ordinary one-way ANOVA. *P<0.05, **P<0.01. ",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(G) Meso-33 cells stably transduced with the indicated shRNAs targeting NEDD4L or a scrambled shRNA were then transduced with vector or Merlin prior to the BrdU incorporation assay. The percentage of BrdU positive cells was quantified. Mean±s.e.m, N=3 biological repeats, two-way ANOVA.",
    "ncbi_link": "NEDD4L: 23327
Merlin: 4771"
  },
  {
    "caption": "(H) FC-1801 cells stably transduced with vector or the indicated Merlin forms were subjected to the sphere formation assay. Scale bar = 500 μm. (I) The number of spheres in each well from (H) was quantified. Mean±s.e.m, N=3 biological repeats, paired t-test. **P<0.05. ",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(J) FC-1801 cells stably transduced with vector or the indicated Merlin forms were subcutaneously injected into nude mice. Tumor sizes in each group were quantified and plotted. Mean±s.e.m, NVector=8 mice, NWT=10 mice, NK396R=10 mice, NS518D=8 mice, two-way ANOVA. P values of the last measurements (day 37 after injection) are shown. *P<0.05, **P<0.01. (K) Tumors were collected when the vector group in (J) reached the end point (day 37 after injection). ",
    "ncbi_link": "Merlin: 4771"
  },
  {
    "caption": "(H-H'') Live wing discs expressing UAS-RFP anterior to the compartment boundary, under the control of ptc-Gal4, were incubated in DiBAC, showing that the stripe of increased DiBAC fluorescence coincides with the posterior edge of ptc expression. White arrowhead in (H) indicates the stripe in the wing pouch; yellow arrowheads indicate the stripe in the dorsal and ventral hinge.",
    "ncbi_link": "Gal4: 855828
ptc: 35851"
  },
  {
    "caption": "(D, E) Expression of rpk RNAi using dpp-Gal4 results in diminished DiBAC fluorescence along the A-P compartment boundary (white arrowhead), while increased fluorescence at the D-V boundary in the A compartment is still observable (yellow arrowhead).",
    "ncbi_link": "dpp: 33432
Gal4: 855828
rpk: 40580"
  },
  {
    "caption": "(A-A''') Immunostaining of discs expressing ptc>RFP with antibodies to Rpk and ATPα showing elevated levels of both proteins anterior to the compartment boundary. White arrowheads indicate approximate position of the A-P compartment boundary.",
    "ncbi_link": "RFP: 
ptc: 35851"
  },
  {
    "caption": "(B-C') L3 discs that are temperature-sensitive for hh following shift to the restrictive temperature for 12 h show loss of increased expression of Rpk (B, B') and ATPα (C, C') anterior to the compartment boundary. Controls shown in Figure EV2. White arrowheads indicate approximate position of the A-P compartment boundary.",
    "ncbi_link": "hh: 42737"
  },
  {
    "caption": "(D-E''') Clones of cells expressing a constitutively activated form of the transcription factor Ci show elevated Rpk and ATPα expression in the anterior compartment (white box) as well as the posterior compartment (yellow arrowhead). (E-E''') A single clone in the A compartment is shown at higher magnification.",
    "ncbi_link": "Ci: "
  },
  {
    "caption": "(G-G') A clone of cells in the anterior compartment expressing ptc RNAi following incubation in DiBAC. The clones also express RFP.",
    "ncbi_link": "ptc: 35851"
  },
  {
    "caption": "(B-C) Effect of expressing an RNAi against the ENaC channel rpk in the dorsal compartment of the disc using ap-Gal4. Knockdown of Rpk in the dorsal compartment results in decreased accumulation of the Hh signal transducer Smo (B, B'), and the activator form of Ci (B, B''). The expression of ptc, visualized using an anti-Ptc antibody (C), a downstream target gene of Hh signaling, is also diminished. The Rpk RNAi line BL:39053 is used in all panels shown, but the phenotype was validated with a second RNAi line (BL:25847).",
    "ncbi_link": "ap: 35509
Gal4: 855828
rpk: 40580
Rpk: 40580"
  },
  {
    "caption": "(A-C) Localization of Smo protein (blue) following expression of 71B-Gal4 (A), 71B-Gal4 and UAS-NaChBac (B) or 71B-Gal4 and UAS-Kir2.1 (C). Expression of the sodium channel NaChBac increases membrane localization of Smo while expression of the potassium channel Kir2.1 reduces membrane localization, and increases cytosolic Smo (B, C).",
    "ncbi_link": "NaChBac: 
Gal4: 855828
Kir2.1: 3759"
  },
  {
    "caption": "(E, F) Expression of the Hh target gene ptc is visualized using anti-Ptc immunostaining. Compared to 71B-Gal4 (E), Ptc expression is increased in glands expressing 71B-Gal4 and UAS-NaChBac (F).",
    "ncbi_link": "NaChBac: 
Gal4: 855828"
  },
  {
    "caption": "(D-E') Discs expressing the red-light activated channelrhodopsin ReaChR under control of ap-Gal4 were raised on a 12hr light/dark cycle, dissected and stained for Smo protein (D, D') or Ptc protein (E, E').",
    "ncbi_link": "ap: 35509
Gal4: 855828"
  },
  {
    "caption": "B. DIS3  expression in total cell lysates of control (siCTRL) and DIS3 U2OS  silenced cells (siDIS3) was analyzed by Western blot upon rescue with empty vector (EV) or DIS3  expressing vector (DIS3). Lamin B was used as the loading control.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "C. Representative images of comet assays  performed under alkaline conditions in U2OS  cells transfected with siCTRL or siDIS3 and then infected with a vector expressing DIS3  (DIS3) or an empty vector (EV). Quantitative analysis of comet tail  lengths for each condition. Plots represent three biological replicates, with more than 150 cells for each point. The analysis is performed using Casplab software, error bars indicate s.e.m. (n=3). **** p-value < 0.0001. ns= not statistically significant, two-way ANOVA, scale bar is 200 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "D. Immunostaining  against RPA  in U2OS  cells transfected with siCTRL or with siDIS3 and 48 hours later infected with a vector expressing DIS3  (DIS3) or an empty vector (EV). The averages of foci number per cell were calculated from three independent experiments using Cell Profiler software. At least 150 cells were counted for each point, error bars indicate s.e.m. (n=3). * p-value < 0.05. ns= not statistically significant, two-way ANOVA, scale bar is 10 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "A. Immunostaining  with S9.6 (green) and DAPI  (blue) in U2OS  cells, transfected for 48 hours with siCTRL or siDIS3 and then mock-treated (UNTR) or treated with  RNase H  or RNase III for 1 hour before fixation. Histograms show S9.6 signal intensity per cell, error bars indicate s.e.m. (n=3, biological replicates). More than 150 cells were counted, and error bars indicate s.e.m. (n=3 biological replicates).). **** = p < 0.0001, *** = p < 0.001, ns = not statistically significant, two-way ANOVA, scale bar is 10 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "B. Immunostaining  with J2 (green) and DAPI  (blue) in U2OS  cells, as in panel A). More than 150 cells were counted, and error bars indicate s.e.m. (n=3 biological replicates). For all conditions, differences between siCTRL and siDIS3 were not statistically significant, two-way ANOVA, scale bar is 10 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "C. Dot blot  analysis of DNA:RNA hybrids formation: serial dilutions (750 ng, 375 ng, 187,5 ng, 93,75 ng, 46,87 ng) of genomic DNA extracted from WT or DIS3  silenced U2OS  cells and pre-treated with RNase H, RNase III or mock treated, were arrayed on a membrane and probed using the S9.6 antibody. The histogram shows the S9.6 signal quantification in 3 biological replicates, error bars indicate s.e.m., normalized on SYBR®-Gold signal (Adj. Vol.), using Image lab software. *** = p < 0.001, ** = p < 0.01, ns= not statistically significant, two-way ANOVA.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "D. DRIP-qPCR   analysis at four different R-loops sites, RPL13A, ACTB, ENSA, and TRIM33  in U2OS  cells transduced with shScr or shDIS3 and treated or not with  RNase H. Results are shown as mean + s.e.m of three independent experiments.**** = p < 0.0001, *** = p < 0.001, * = p < 0.05, two-way ANOVA.",
    "ncbi_link": "ACTB: 60
DIS3: 22894
ENSA: 2029
RPL13A: 23521
TRIM33: 51592"
  },
  {
    "caption": "E. Representative pictures of comet assays performed under alkaline conditions in U2OS  cells transfected for 48 hours with siCTRL or siDIS3, untreated (UNTR) or treated with RNase H (RNase H). Tail  moments analysis was performed using Casplab software, error bars indicate s.e.m. Plots represent three biological replicates, with 150 cells for each cell line. **** = p < 0.0001, ns= not statistically significant, two-way ANOVA, scale bar is 200 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "A. U2OS  cells were transfected with siCTRL or with siDIS3 and 48 hours later were irradiated (IR) or left untreated (NO IR). Cells were fixed 4 hours after IR  and stained  for RAD51. Histograms show foci number per cell, analyzed with Cell Profiler. The average number of foci per cell was calculated from three independent experiments. At least 200 cells were counted for each point, error bars indicate s.e.m. (n=3). * = p < 0.05, two-way ANOVA, ns= not statistically significant, scale bar is 10 µ",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "D. Representative pictures of alkaline comet assays performed in U2OS  silenced (siDIS3) or not (siCTRL) for DIS3, at sequential  time points  after exposure to 3 Gy irradiation. Relative comet tail  moments were plotted for siCTRL (black circles) and siDIS3  (red circles). Analysis was performed using Casplab software, error bars indicate s.e.m. Plots represent three biological replicates, with more than 150 cells for each siRNA. **** = p < 0.0001, ** = p < 0.001, ns= not statistically significant, two-way ANOVA, scale bar is 20 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "F. Representative images of HPRT   negative mutants in HT1080  cells infected with scramble shRNA (shScr) or shRNA against DIS3  (shDIS3). Histograms show the  mutation frequency  and the  deletion length  of DIS3  WT (shScr) and DIS3  depleted cells (shDIS3) after I-SceI  induced DSB. Error bars represent s.e.m. (n=3). *** = p < 0.001, ns= not statistically significant Student t-test.",
    "ncbi_link": "DIS3: 22894
HPRT: 3251"
  },
  {
    "caption": "A. U2OS  cells were transfected with siCTRL or with siDIS3 and 48 hours later were 3 Gy irradiated   (IR) or left untreated (NO IR). Cells were fixed 4 hours after IR  and stained  for BRCA1. Histograms show foci number per cell, analyzed with Cell Profiler. The average number of foci per cell was calculated from three independent experiments. At least 200 cells were counted for each point, error bars indicate s.e.m. (n=3 biological replicates). ** = p < 0.01, ns= not statistically significant, two-way ANOVA, scale bar is 10 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "C. Representative images of BRCA1 staining  on U2OS  cells transfected with siCTRL or with siDIS3. 48 hours after transfection cells were irradiated and 4 hours later were treated with  RNase H or left untreated (UNTR). Histograms show the average foci number per cell from three independent experiments analyzed with Cell Profiler. At least 200 cells were counted for each point, error bars indicate s.e.m. (n=3). ** = p < 0.01, ns= not statistically significant, one-way ANOVA, scale bar is 10 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "D. Representative pictures of comet assays performed under alkaline conditions in U2OS  cells, silenced (siDIS3) or not (siCTRL) for DIS3  untreated (UNTR) or treated with RNase H (RNase H). Relative comet tail  moments are plotted for siCTRL (black circles) and siDIS3 (red circles). Analysis was performed using Casplab software, error bars indicate s.e.m. Plots represent three biological replicates, with 150 cells for each siRNA. **** = p < 0.0001, one-way ANOVA, scale bar is 20 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "A. Representative pictures of comet assays performed under alkaline conditions in DIS3  WT MM  cell lines  MM.1S  and RPMI-8226 (RPMI), and in DIS3  mutated MM  cell lines PCM6  and OPM2, untreated (UNTR) or treated with RNase H (RNase H). Tail  moments analysis was performed using Casplab software, error bars indicate s.e.m. Plots represent three biological replicates, with 150 cells for each cell line. **** = p < 0.0001 ns= not statistically significant, two-way ANOVA, scale bar is 20 µm.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "A. Relative mRNA expression level of interferon genes IFI6, ISG15, IFITM1, IFIT3, IFI27, MCL1, cGAS, and STING  in OPM2  cells infected with a vector expressing DIS3  (DIS3) or an empty vector (EV). Values are relative to housekeeping gene expression, normalized on EV, and represent SE of three biological replicates. *** = p < 0.001, ** = p < 0.01, multiple t-tests.",
    "ncbi_link": "cGAS: 115004
DIS3: 22894
IFI27: 3429
IFI6: 2537
IFIT3: 3437
IFITM1: 8519
ISG15: 9636
MCL1: 4170
STING: 340061"
  },
  {
    "caption": "Differentially expressed genes (DEGs) between mutant and WT samples; p-values are from limma and false-discovery rate (FDR) is calculated using the Benjamini-Hochberg procedure; FDR < 0.05 was used as cut off. Functional annotation analysis by IPA of the DEGs between DIS3  mutant and WT samples based on FDR cut-off. (C) Volcano plot of DEGs between mutant and WT samples; labeled genes are the IFN-related genes with an FDR < 0.05 (red horizontal line) and absolute log 2-fold change above or below 0.5 (red vertical lines), respectively; additional representative IFN-related genes are also labeled.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "(F) Violin plot of the number of non-synonymous (NS) mutation load comparison between DIS3  mutant versus DIS3 WT performed on the entire CoMMpass dataset, including 853 MM patients, 88 presenting DIS3  mutations (all samples) and on the CoMMpass dataset, stratified according to the intensity of the IFN   responsiveness (clusters C1, C2, C3). Wilcoxon rank-sum test was used for comparison between DIS3  mutant vs WT. **** = p <, ** = p < 0.01, * = p < 0.05. Black color dots represent the median in each group.",
    "ncbi_link": "DIS3: 22894"
  },
  {
    "caption": "(A) Immunoblotting against the GFP or the GAPDH of proteins extracted from HEK293 cells transfected for 24 hours with 80 G4C2 repeats embedded in the human sense C9ORF72 and fused in all three possible frames with the GFP deleted of its ATG.",
    "ncbi_link": "GFP: 
C9ORF72: 203228"
  },
  {
    "caption": "(C, D) Immunoblotting against the GFP (C) or the HA tag (D) or the GAPDH of proteins extracted from HEK293 cells transfected for 24 hours with 3, 20 or 80 G4C2 repeats embedded in the human sense C9ORF72 sequence fused to the GFP in the GA frame.",
    "ncbi_link": "GFP: 
C9ORF72: 203228"
  },
  {
    "caption": "(E) Immunoblotting against the GFP or the GAPDH of proteins extracted from HEK293 cells transfected with either a wild type or mutant (AGG into CGG) construct containing 80 G4C2 repeats embedded in sense C9ORF72 fused to the GFP in the GR frame.",
    "ncbi_link": "GFP: 
C9ORF72: 203228"
  },
  {
    "caption": "(A) Immunoblotting against the HA tag or the GAPDH of proteins extracted from HEK293 cells transfected for 24 hours with 100 C4G2 repeats embedded in the human antisense C9ORF72 and fused in all three possible frames with a HA tag.",
    "ncbi_link": "HA: 
C9ORF72: 203228"
  },
  {
    "caption": "(C, D) Immunoblotting against the GFP (C) or the HA tag (D) or the GAPDH of proteins extracted from HEK293 cells transfected for 24 hours with 3, 10 or 100 C4G2 repeats embedded in the human antisense C9ORF72 sequence fused to the GFP in the PG frame.",
    "ncbi_link": "GFP: 
C9ORF72: 203228"
  },
  {
    "caption": "(A) Cell viability (TO-PRO-3 FACS staining) of GT1-7 neuronal cells transfected for 24 hours with either wild type or indicated mutant constructs containing either 80 G4C2 repeats or 100 C4G2 repeats embedded in sense or antisense C9ORF72 fused to the GFP in the GA, PG or GR frame.",
    "ncbi_link": "GFP: 
C9ORF72: 203228"
  },
  {
    "caption": "(B) Immunoblotting against the GFP, endogenous C9ORF72 or the GAPDH of proteins extracted from Neuro2A cells transfected for 24 hours with 80 G4C2 repeats embedded in the human sense C9ORF72 sequence fused to the GFP in the GA frame and with either a control siRNA or a siRNA targeting C9orf72 mRNA.",
    "ncbi_link": "GFP: 
C9ORF72: 203228
C9orf72: 203228"
  },
  {
    "caption": "(C) Immunoblotting against the HA tag, endogenous C9ORF72 or GAPDH of proteins extracted from Neuro2A cells transfected for 24 hours with 100 C4G2 repeats embedded in the human antisense C9ORF72 sequence fused to a HA tag in the PG frame and with either a control siRNA or a siRNA targeting C9orf72 mRNA or treated with Bafilomycin A1 for 15 hours.",
    "ncbi_link": "HA: 
C9ORF72: 203228
C9orf72: 203228"
  },
  {
    "caption": "(D) Immunoblotting against the HA tag, endogenous C9ORF72 or GAPDH of proteins extracted from Neuro2A cells transfected for 24 hours with 80 G4C2 repeats embedded in the human sense C9ORF72 sequence fused to a HA tag in the GR frame and with either a control siRNA or a siRNA targeting C9orf72 mRNA or treated with Bafilomycin A1 for 15 hours.",
    "ncbi_link": "HA: 
C9ORF72: 203228
C9orf72: 203228"
  },
  {
    "caption": "(E) Cell viability (TO-PRO-3 FACS staining) of GT1-7 neuronal cells co-transfected for 24 hours with either a control siRNA or a siRNA targeting C9orf72 mRNA and wild-type or mutants constructs containing either 80 G4C2 repeats or 100 C4G2 repeats embedded in sense or antisense C9ORF72 fused to the GFP in the GA, PG or GR frame.",
    "ncbi_link": "GFP: 
C9orf72: 203228
C9ORF72: 203228"
  },
  {
    "caption": "(A) Left panel, immunoblotting against the HA tag or the GAPDH of proteins extracted from Neuro2A cells transfected for 24 hours with a construct expressing 80 G4C2 repeats embedded in the human sense C9ORF72 sequence fused to a HA in the GA frame and treated with 10 µM of the indicated compound for 15 hours. Right panel, quantification of polyGA expression relative to the GAPDH.",
    "ncbi_link": "HA: 
C9ORF72: 203228"
  },
  {
    "caption": "(B) Left panel, immunoblotting against the HA tag or the GAPDH of proteins extracted from Neuro2A cells transfected for 24 hours with a construct expressing 100 C4G2 repeats embedded in the human antisense C9ORF72 sequence fused to a HA tag in the PG frame and treated with 10 µM of the indicated compound for 15 hours. Right panel, quantification of polyPG expression relative to the GAPDH.",
    "ncbi_link": "HA: 
C9ORF72: 203228"
  },
  {
    "caption": "(C) Cell viability (TO-PRO-3 FACS staining) of GT1-7 neuronal cells treated with 1, 3 or 10 µM of promethazine and co-transfected for 24 hours with either a control siRNA or a siRNA targeting C9orf72 mRNA and a construct expressing either 80 G4C2 repeats or 100 C4G2 repeats embedded in sense or antisense C9ORF72 fused to the GFP in the GA or PG frame.",
    "ncbi_link": "GFP: 
C9orf72: 203228
C9ORF72: 203228"
  },
  {
    "caption": "B WT, Ripk3-/-, Mlkl-/-, Tnfr1-/- and Traf2-/- MDFs were untreated (UT) or treated with TSI for 3 hrs. Nec-1 and GSK872 were added to inhibit RIPK1 and RIPK3 kinase activities respectively.",
    "ncbi_link": "Mlkl: 74568
Ripk3: 56532
Tnfr1: 71609
Traf2: 22030"
  },
  {
    "caption": "E RIPK3-gyrase were inducibly expressed in Ripk3-/- MDFs by doxycycline (dox) for 5 hrs, and cells were then treated ± combination of TSI, or coumermycin (coum) for 3 hrs.",
    "ncbi_link": "Ripk3: 56532"
  },
  {
    "caption": "B WT USP21-CaaX and USP21C221R-CaaX (CR) were inducibly expressed in WT MDFs by doxycycline for 5 hrs. Ubiquitylated proteins were enriched followed by TSI stimulation and cellular fractionation. All fractions were analysed by Western blot and probed with antibodies as indicated. Representative of three independent experiments.",
    "ncbi_link": "USP21: 30941"
  },
  {
    "caption": "A WT and R105AD106A mutant MLKL were inducibly expressed in Mlkl-/- MDFs by doxycycline, at the same time cells were untreated (UT) or treated with TSQ for 6 hrs. Cells were fractionated into cytosol (C) and crude membrane (M). Fractions were analysed by BN- or SDS-PAGE, Western blot and probed with the indicated antibodies. Representative of three independent experiments. B Cell lysates from (A) were subjected to UBA-pull down and analysed as described above.",
    "ncbi_link": "Mlkl: 74568"
  },
  {
    "caption": "A WT and E109AE110A mutant MLKL were inducibly expressed in Mlkl-/- MDFs by doxycycline, cells were untreated or treated with TSQ for 6 hrs (please note that the same WT control was used in Fig. EV3A). Cell death was measured by PI staining based on flow cytometry. Data are plotted as mean ± SEM of three independent experiments. B Cellular fractions from (A) were analysed by Western blot from BN-PAGE or SDS-PAGE using antibodies as indicated. The same WT control was used in Fig. 4A. Representative of three independent experiments. C Cell lysates from (A) were subjected to UBA-pull down and analysed as described above.",
    "ncbi_link": "Mlkl: 74568"
  },
  {
    "caption": "D N-FLAG MLKL were inducibly expressed in Mlkl-/- MDFs by doxycycline overnight, and cells were treated with TSI for indicated time, followed by UBA-pull down. Representative of three independent experiments. E N-FLAG MLKL were inducibly expressed in Mlkl-/- MDFs by doxycycline for 16 hrs. Cells were stimulated ± TSI for 3 hrs after withdrawal of doxycycline. Then TSI medium was removed and replaced to medium containing inhibitors Bafilomycin A1 (BAF), PS341 (PS) or left untreated (UT). IDN-6556 was added to all conditions to block apoptosis. Cells were collected 0, 2, 4, 6 hrs after medium replacement, followed by UBA-pull down. Representative of three independent experiments.",
    "ncbi_link": "Mlkl: 74568"
  },
  {
    "caption": "B WT and 4KR mutant MLKL were inducibly expressed in Mlkl-/- MDFs by doxycycline for 6 hrs and cells were untreated (UT) or treated with TSI, followed by UBA-pull down. Representative of three independent experiments.",
    "ncbi_link": "Mlkl: 74568"
  },
  {
    "caption": "D MLKL-/- HT29 cells stably transfected with constructs encoding human MLKL-USP21 and MLKL-USP21C221R, were treated with doxycycline, NSA (1 μM), TSI or combinations thereof (added simultaneously). Sytox Green positive cells were quantified in real time by live cell imaging. Data are plotted as mean ± SEM of six independent experiments. (A red dashed line is shown to highlight the delay in death kinetics upon treatment with NSA). E Human MLKL-USP21 and MLKL-USP21C221R were inducibly expressed in MLKL-/- HT29 cells by doxycycline (10 ng/mL) for 16 hrs, TSI was added for the indicated times but all samples were collected 25 hrs post-induction, followed by UBA-pulldown . Representative of three independent experiments.",
    "ncbi_link": "MLKL: 197259
USP21: 27005"
  },
  {
    "caption": " Total IgG ELISA titers expressed as area under the curve (AUC) against homologous Cal/7/9 virus of pre-immune and pre-challenge sera of individual animals of the indicated vaccine groups (AAV-HA, -cHA, -GFP, WIV n = 18, AAV-NP n = 11). Background reactivity of pooled AAV-GFP pre-challenge serum is shown as dashed line. ELISAs were performed in technical duplicates. ",
    "ncbi_link": "HA: 23308115
NP: 23308118"
  },
  {
    "caption": " IgA ELISA titers in post-challenge lung homogenates against Cal/7/9 of individual mice of the indicated vaccine groups (AAV-HA, -cHA, -GFP, -NP, WIV n = 11). of the Cal/7/9 (blue symbols) and PR8 low dose (red symbols) challenge groups. ELISAs were performed in technical duplicates. ",
    "ncbi_link": "HA: 23308115
NP: 23308118"
  },
  {
    "caption": " A Immunoblot analysis of purified H1N1 viruses A/California/7/2009 (Cal/7/9), A/Brevig Mission/1/1918 (BM/1/1918), A/Puerto Rico/8/1934 (PR8) or A/Brisbane/59/2007 (Bris/59/7) separated under reducing and denaturing conditions. Uncleaved HA0 and cleavage products HA1 and HA2 were detected with pooled pre-challenge sera (AAV-HA, -cHA, -GFP , WIV n = 18, AAV-NP n = 11) as indicated (n = 3).",
    "ncbi_link": "GFP: 
HA: 23308115
NP: 23308118"
  },
  {
    "caption": " C to F Binding of C179 (C), or antibodies present in AAV-HA (D), AAV-cHA (E) or WIV (F) pooled pre-challenge sera (n = 18 mice per group) to Cal/7/9 or PR8 virus after incubation of the virions at pH = 7.2, 5.8, 5.4, 5.0, 4.4 or 4.4+DTT to induce conformational changes in HA or remove the HA1 subdomain. Mean ± SD (n = 3, in technical triplicates). Statistical significance between pH = 7.2 and other conditions was determined using Kruskal-Wallis test with Dunn's multiple comparison testing (*p<0.05, **p<0.01). ",
    "ncbi_link": "HA: 23308115"
  },
  {
    "caption": " A and B Influenza virus specific activation of the murine FcγRI, FcγRII, FcγRIII and FcγRIV by antibodies in pooled pre-challenge sera (AAV-HA, -cHA, -GFP, WIV n = 18, AAV-NP n = 11 mice per group). MDCKII cells were infected with Cal/7/9 (A) or PR8 (B) before mouse serum and FcγR-expressing reporter cells were added. Influenza specific Fc-FcγR interaction induces the production of IL-2 in the FcγR-expressing reporter cell, which was measured by anti-IL2 ELISA (n = 3, technical duplicates). Mean ± SE. ",
    "ncbi_link": "GFP: 
HA: 23308115
NP: 23308118"
  },
  {
    "caption": " C HA-specific activation of FcγR by AAV-HA, AAV-cHA or WIV pooled pre-challenge sera (n = 18 mice per group). MDCKII cells were transfected with wildtype HA (pAAV-HA) or a stalk-only HA (pAAV-mHL1) before mouse serum and FcγR-I-expressing reporter cells were added (n = 2, technical duplicates). Mean ± SE. ",
    "ncbi_link": "HA: 23308115"
  },
  {
    "caption": " A to F Mice were vaccinated three times with AAV-vectors or two times with WIV and then challenged with a lethal dose of homologous influenza virus (Cal/7/9) (A, B; n = 5) or two different lethal doses of the heterologous PR8 strain (C, D; n = 6 and E, F; n = 7). Survival was monitored over a 14-day period and is depicted as Kaplan-Meier plot (A, C, E). Weight loss was determined during the 14-day period, which is shown in relation to the weight at day 0 (B, D, F). Mean ± SE. Statistical significance between negative control group (AAV-GFP) or WIV group (E) and each vaccine group was determined using Log-Rank (Mantel-Cox) test (*p<0.05, **p<0.01). ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " C to E Clinical score (C), body temperature (D), and relative weight (E) during challenge period. Statistical significance between pre-immune and immune sera was determined using Friedman test with Dunn's multiple comparison testing (AAV-HA ##p<0.01; AAV-cHA §§p<0.01; AAV-GFP $p<0.05; $$p<0.01; QIV *p<0.05;). Mean ± SD ",
    "ncbi_link": "GFP: 
HA: 23308115"
  },
  {
    "caption": " F Virus titers in nasal turbinates (NT), trachea or lung homogenates. Statistical significance between AAV-GFP and vaccine groups was determined using Kruskal-Wallis test with Dunn's multiple comparison testing (*p<0.05). Lines indicate the GMT. Assays were performed in technical duplicates. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B Sequencing chromatograms depicting the identified 22 nucleotide deletion (c.346_*7del) identified in Subject 1 (S1), the heterozygous state of the deletion in the father, and the wild-type NDUFC2 sequence in Control DNA.",
    "ncbi_link": "NDUFC2: 4718"
  },
  {
    "caption": "C Sequencing chromatograms depicting the identified missense variant (c.173A>T; p.(His58Leu)) in Subject 3 (S3) and the wild-type NDUFC2 sequence in Control DNA.",
    "ncbi_link": "NDUFC2: 4718"
  },
  {
    "caption": "A NDUFC2 mRNA transcript levels in fibroblast cell lines of controls (white), Subject 1 (grey) and Subject 3 (black). Quantification of NDUFC2 mRNA transcript levels (normalised to ACTB) showed diminished transcript levels in Subject 1 while transcript levels were unaffected in Subject 3. Bars correspond to standard deviations of two independent experiments, performed in duplicate and analysed by Student's t-test; *p<0.05.",
    "ncbi_link": "ACTB: 60
NDUFC2: 4718"
  },
  {
    "caption": "C Western blot analysis of whole cell lysates from controls (C1 and C2) and subject cell lines (S1 and S3) that were either untransduced (-) or transduced with the lentiviral vector (pLVX) containing wild-type NDUFC2 (+). Transduced cell lines were either uninduced or induced with 100 or 200 ng/ml doxycycline (for 48 and 96 hours respectively) where indicated.",
    "ncbi_link": "NDUFC2: 4718"
  },
  {
    "caption": "D BN-PAGE analysis of OXPHOS complex assembly in enriched mitochondria isolated from controls (C1 and C2) and subject cell lines that were either untransduced (-) or transduced with the lentiviral vector (pLVX) containing wild-type NDUFC2 (+). Transduced cell lines were either uninduced or induced with 200 ng/ml doxycycline for 72 hours.",
    "ncbi_link": "NDUFC2: 4718"
  },
  {
    "caption": "A Complexome profiling identified assembly intermediates in subject cells with NDUFC2 variants. Complexes from mitochondrial membranes of Control, Subject 1 and Subject 3 fibroblasts were separated by BN-PAGE (Fig EV2) and analysed by complexome profiling. Sample preparation, mass spectrometry, data processing and raw data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (Vizcaíno et al., 2013) with the dataset identifier <PXD014936>. Assignment of complexes: III, complex III; IV, complex IV; III/IV, supercomplex containing dimer of complex III and 1-2 copies of complex IV; S, supercomplex containing complex I, dimer of complex III and 1-4 copies of complex IV. Assembly intermediates are highlighted in dashed boxes indicating stalled complex I assembly. In subject complexomes, various stalled complex I intermediates are assembled: ND4 module (blue dashed box); Q-TIMMDC1-NDUFA13 complex I intermediate (orange dashed box); and Q-TIMMDC1-NDUFA13-MCIA (green dashed box). In control complexome, the Q module (orange dashed box) is assembled without TIMMDC1 or NDUFA13. Complex I modules are denoted according to Stroud and colleagues (Stroud et al., 2016).",
    "ncbi_link": "NDUFC2: 4718"
  },
  {
    "caption": " I, J. Normal ciliary formation of Rabl2-/- MEFs. MEFs derived from E12.5 mouse embryos were serum-starved for 48 h to induce primary cilia (I). Statistical results (J) were from three independent experiments. Ciliogenesis of at least 200 cells was scored in each experiment and condition. Ciliary lengths of 80 cells were measured in each experiment and condition and the results of the same genotypes were pooled together. K, L. Rabl2 deficiency did not repress ciliary localization of IFT-B. Ciliated MEFs were immunostained for Ift81 and Ift57, two IFT-B subunits (K; see Fig 4F for diagram of IFT-B). Relative intensity of ciliary Ift81 (L), presented in arbitrary unit, was obtained by normalizing to that of corresponding Ac-tub. Four MEF strains prepared respectively from two embryos per genotype were used for quantification. 50 cilia were quantified from each MEF strain and results of the same genotypes were pooled together. ",
    "ncbi_link": "Rabl2: 68708"
  },
  {
    "caption": " Rabl2Q80L inhibited Hh signaling. MEFs from Rabl2-/- E12.5 embryos infected with lentivirus to express GFP, GFP-Rabl2 or GFP-Rabl2Q80L were serum-starved for 24 h and treated with DMSO (mock) or 100 nM SAG for an additional 24 h. Uninfected MEFs from the wildtype littermate embryos served as the positive control. The samples were immunostained to examine ciliary Gli2 The white arrowheads (G) point to ciliary tips. Quantification results were from three independent experiments, each using MEFs from different Rabl2-deficient embryos. Gli2 intensities, presented in arbitrary unit, were measured from at least 22 cilia in each experiment and condition and pooled together. ",
    "ncbi_link": "GFP: 
Rabl2: 68708"
  },
  {
    "caption": " H. Rabl2Q80L inhibited Hh signaling. MEFs from Rabl2-/- E12.5 embryos infected with lentivirus to express GFP, GFP-Rabl2 or GFP-Rabl2Q80L were serum-starved for 24 h and treated with DMSO (mock) or 100 nM SAG for an additional 24 h. Uninfected MEFs from the wildtype littermate embryos served as the positive control. The samples were immunoblotted to examine levels of Gli1 and Gli3 In the samples for immunoblotting (H), GFP-positive cells occupied 82.3% (GFP), 87.3% (GFP-Rabl2), and 81.2% (GFP-Rabl2Q80L), respectively, when 260 cells in each sample were scored. Relative band intensities are shown in red. ",
    "ncbi_link": "GFP: 
Rabl2: 68708"
  },
  {
    "caption": " D, E. Ciliary accumulation of BBS proteins in Rabl2Q80L-expressing RPE1 cells. The white arrows (D) point to positions of cilia. Quantification results (E) were from three independent experiments. At least 100 GFP-positive cells were scored in each experiment and condition. ",
    "ncbi_link": "Rabl2: 68708"
  },
  {
    "caption": " H, I. BBSomes and IFT-B were able to reach the ciliary base through retrograde IFT in the presence of Rabl2Q80L. Ciliary 3NG-Bbs5 (H) or Ift27-GFP (I) in IMCD3 cells co-expressing RFP-Rabl2 or RFP-Rabl2Q80L was live imaged at 4 fps. Snapshots for the ciliary RFP proteins, the first frames from Movies EV2-EV5, corresponding kymographs, and quantification results from the indicated numbers of cilia are presented. For processivity analysis (I), only traceable puncta were scored. ",
    "ncbi_link": "GFP: 
RFP: 
Bbs5: 72569
Ift27: 67042
Rabl2: 68708"
  },
  {
    "caption": " E, F. Rabl2D73GQ80L did not repress ciliary translocation of SMO and GPR161. RPE1 cells expressing GFP-tagged Rabl2Q80L or Rabl2D73GQ80L were serum-starved for 24 h and treated with DMSO (mock) or SAG for an additional 24 h prior to immunostaining (E). The white arrows (E) point to positions of cilia. In quantification results (F), at least 100 cells were scored in each experiment and condition. ",
    "ncbi_link": "GFP: 
Rabl2: 68708"
  },
  {
    "caption": " G. Ciliary Rabl2D73GQ80L did not repress the BBSome export. FLIP assays were performed in RPE1 cells co-expressing 3NG-Bbs5 with RFP-tagged Rabl2Q80L or Rabl2D73GQ80L as depicted in Fig 5F. Photobleaching was executed at t = 0. Quantification results on half-life (t1/2) were from 10 cilia for each condition. ",
    "ncbi_link": "RFP: 
Rabl2: 68708"
  },
  {
    "caption": " F, G. Endogenous Rabl2Q80L entered ciliary shaft to repress the export of the BBSome (Bbs5) and its cargo GPCR (Smo). mEPCs cultured from Rabl2KI/KI and wildtype neonatal mice were fixed at day 7 post serum starvation. Anti-Rabl2 antibody was used to visualize Rabl2 and Rabl2Q80L. Ac-tub or Arl13b served as ciliary marker. Representative micrographs of multicilia (F) and primary cilia (G) are shown. The white arrows point to positions of cilia. ",
    "ncbi_link": "Rabl2: 68708"
  },
  {
    "caption": "g-h) Representative  β-catenin ChIP-qPCR  of indicated target genes in wt and TCF1/LEF1  long isoform double KO (DLKO) clones (g) and Kaiso  KO clones (h) in RPMI8402  cells. Enrichment of each ChIP  is normalized to its respective negative IgG control, indicated by a red-dashed line. DLKO1, DLKO2, KKO1 and KKO2 designate independent single-cell derived clones. Graph represents the mean and sd of 3 technical replicates.",
    "ncbi_link": "LEF1: 51176
TCF1: 6932
Kaiso: 10009"
  },
  {
    "caption": "e) Relative mRNA expression  of β-catenin target genes in the RPMI8402  cell line (right panel) after knockdown of  β-catenin (left panel) compared to control. Graph represents the mean and sd of 6 independent experiments. f) Relative mRNA expression  of  β-catenin target genes in the RPMI8402  cell line after treatment with the  β-catenin inhibitor ICG-001 (10µM, overnight). Graph represents the mean and sd of 3 independent experiments. g) Relative mRNA expression  of  β-catenin target genes in the RPMI8402  cell lines (right panel) after knockdown of ZBTB33/Kaiso  (left panel) compared to control. Graph represents the mean and sd of 3 independent experiments. Data information: Statistical significance was determined by two-sided Student's t test.",
    "ncbi_link": "β-catenin: 1499
Kaiso: 10009
ZBTB33: 10009"
  },
  {
    "caption": "a) Effect of Vincristine  (VCR) treatment on cell viability  of RPMI8402  cells transduced with sh β-catenin  or sh-control. Dose-response curves  represent the logistic fitting and individual points correspond to mean ± SD of three independent experiments. *** p ≤ 0.001 of IC50  comparison with respect to sh control Data information: For all applicable figure panels, data represent mean ± SD of three independent experiments. Statistical significance was determined by two-sided Student's t test for a (at day 0)",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "EphA2 (total and phosphorylated), RSK1/2 and GPRC5A in TYK-nu were assessed by immunoblotting after RSK1/2 knockdown for 2 d and following treatment with 0-5 μM cisplatin for 72 h. Asterisks indicate unspecific bands.",
    "ncbi_link": "RSK1: 6195"
  },
  {
    "caption": "EphA2 (total and phosphorylated), RSK1/2 and GPRC5A and these proteins coupled with PARP and PCNA in TYK-nu.R were assessed by immunoblotting after RSK1/2 knockdown for 2 d and following treatment with 0-5 μM cisplatin for 72 h. Asterisks indicate unspecific bands.",
    "ncbi_link": "RSK1: 6195"
  },
  {
    "caption": "Chart illustrates the viability of the RSK1/2 depleted TYK-nu.R after cisplatin treatment. N = 3.",
    "ncbi_link": "RSK1: 6195"
  },
  {
    "caption": "Confocal micrographs show cleaved caspase-3 (clCasp3, green), mRFP (orange) and phalloidin (F-actin, red; only shown for CAF) in 3D OVCAR8-RFP and OCKI_p22 CAF mono- and co-cultures treated without or with 20 µM cisplatin or 25 µM LJH685 alone or in combination for 20 h. Scale bars: 100 μm.",
    "ncbi_link": "RFP: "
  },
  {
    "caption": "Kaplan Meier survival estimates for the PFS of patients with high or low (top 25% vs bottom 25%) GPRC5A (F), EPHA2 (G), GPRC5A+EPHA2 (H) and GPRC5A+EPHA2+RSK1(RPS6KA1)+RSK2(RPS6KA3) combined (I) mRNA expression. Mean PFS for GPRC5A+EPHA2high was 15 months vs 26 months for GPRC5A+EPHA2low (H). Mean PFS for GPRC5A+EPHA2+RPS6KA1/3 high was 14 months vs 31 months for GPRC5A+EPHA2+RPS6KA1/3low (I).",
    "ncbi_link": "EPHA2: 1969
GPRC5A: 9052
RPS6KA1: 6195
RSK1: 6195
RPS6KA3: 6197
RSK2: 6197"
  },
  {
    "caption": "Possible correlation between AR- and UPR-associated gene expression was assessed in the global gene expression data available in the TCGA Prostate Adenocarcinoma cohort (n = 190) (http://www.cbioportal.org/public-portal/index.do). Tumors were stratified according to AR status into three groups, that is ARlow (n = 60), ARmedium (n = 70), and ARhigh (n = 60). The levels of UPR gene expression in the three groups were compared using Pearson's correlation analysis by the R software and presented as a heatmap. There were significant differences between the three groups (Supplementary Table S2).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "The expression profiles of some prominent UPR genes from the data in (A), including ERN1 (IRE1), EDEM1, ATF6, and DNAJC3 (P58IPK), are presented. P-values of the different genes are given.",
    "ncbi_link": "ATF6: 22926
DNAJC3: 5611
P58IPK: 5611
EDEM1: 9695
ERN1: 2081
IRE1: 2081"
  },
  {
    "caption": "A, B mRNA expression levels in LNCaP cells for the indicated genes were investigated using quantitative PCR (qPCR). Controls were treated with vehicle for 84 h and set to 100. Data represent the mean of three independent experiments in triplicate, and bars represent SE. P-values ranged between 1.66 × 10−5 and 0.025, and IRE1α expression in R1881 48 h was *P = 0.013 with respect to vehicle-treated cells using unpaired Student's t-test.",
    "ncbi_link": "IRE1α: 2081"
  },
  {
    "caption": "C-E IRE1α, XBP-1S, and XBP-1U mRNA in CWR22xenografts grown in nude mice and collected at the indicated times after castration. The value at t = 0 was set to 1. Columns represent the mean of at least three independent tumors for each time point, and bars represent SE. P-values ranged between 5.7  ×  10−10 and 0.0002. IRE1α expression at 48 h post-castration was 3.17 × 10−6 with respect to t = 0 using unpaired Student's t-test.",
    "ncbi_link": "IRE1α: 2081
IRE1α: 78943
XBP-1: 22433
XBP-1: 7494"
  },
  {
    "caption": "After starvation, LNCaP cells were transfected with control (CTRL) siRNA or AR siRNA. Cells were then treated with R1881 for the indicated times. Controls were treated with vehicle for 48 h.A Expression level of AR mRNA upon siRNA treatment for 48 h assessed by qPCR in LNCaP cells. Expression in cells transfected with CTRL siRNA was set to 1. Bars represent SE with *P = 0.001 indicating significant difference between AR siRNA- and control siRNA-transfected cells using paired Student's t-test.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "After starvation, LNCaP cells were transfected with control (CTRL) siRNA or AR siRNA. Cells were then treated with R1881 for the indicated times. Controls were treated with vehicle for 48 h.B-E Same as in (A), but mRNA expression levels of the indicated UPR genes were determined by qPCR at indicated time points after R1881 stimulation. Expression in cells transfected with CTRL siRNA was set to 100. Bars represent SE. P-values are shown indicating significant difference between AR siRNA- and control siRNA-transfected cells using unpaired Student's t-test.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "After starvation, LNCaP cells were transfected with control (CTRL) siRNA or AR siRNA. Cells were then treated with R1881 for the indicated times. Controls were treated with vehicle for 48 h.F Expression of the indicated proteins under conditions indicated on the top label was determined by Western blot analysis. Representative blots for three independent experiments are shown.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "A Knockdown of IRE1α or XBP-1 leads to a decrease in cell survival. LNCaP cells were transfected with siRNA targeting either IRE1α or XBP-1 (5 nM) and starved in 2% CT-FCS medium for 3 days before cell viability was measured using the CCK-8 assay. The graph is representative of one experiment in triplicate and was repeated three times with similar results. Error bars represent SD with *P = 6.6 × 10−5 and 4.5 × 10−5 for comparison between Ctrl and siRNA against IRE1α and XBP-1, respectively, using paired Student's t-test.",
    "ncbi_link": "IRE1α: 2081
XBP-1: 7494"
  },
  {
    "caption": "B XBP-1 rescues the growth defect of siIRE1α-transfected LNCaP cells. LNCaP cells were transfected with 5 nM of indicated siRNA using Lipofectamine RNAiMax reagent. One day after siRNA transfection, the cells were transfected with either vector control (Empty) or Flag-XBP-1S (XBP-1S). Three days after transfection, cells were harvested for western blot analysis or cultured for three more days before being applied to cell proliferation assay using the CCK-8 reagent. The data are representative of two experiments in triplicate. Error bars represent SE. *P = 0.02, **P = 8.54 × 10−7 using paired Student's t-test.",
    "ncbi_link": "IRE1α: 2081
XBP-1: 7494"
  },
  {
    "caption": "C, D IRE1α and XBP-1 knockdown inhibits clonogenic capacity of LNCaP cells. Control LN-Scr (Scr), LN-shIRE1 (shIRE1), or LN-shXBP1 (shXBP-1) cells were cultured for 3 weeks. The colonies formed were stained with crystal violet and photographed. The extent of IRE1α and XBP-1 knockdown was determined by Western blot analysis. The area covered by colonies was quantified using the Gene Tools software (SynGene). The data are representative of three experiments in triplicate. Error bars represent SEM. *P = 4.38 × 10−7 and **P = 3.39 × 10−20 using paired Student's t-test.",
    "ncbi_link": "IRE1: 2081
IRE1α: 2081
XBP-1: 7494
XBP1: 7494"
  },
  {
    "caption": "E Growth analysis of xenograftedLNCaPtumors in nude mice. LNCaP cells expressing shRNA against IRE1α (LN-shIRE1), XBP1 (LN-shXBP-1), or control shRNA (LN-Scr) were subcutaneously implanted into both flanks of male nude mice (6 mice per group). Tumor size was measured at the indicated time points. Representative pictures of the tumors at harvest are shown. Error bars indicate SEM. *P = 0.03 for shIRE1 at week 7, P = 0.02 for shXBP-1 at week 7, **P = 0.01 for both shIRE1 and shXBP-1 at week 8 using unpaired Student's t-test.",
    "ncbi_link": "IRE1: 2081
IRE1α: 2081
XBP-1: 7494
XBP1: 7494"
  },
  {
    "caption": "F PCNA immunostaining in tumors from animals bearing LN-shIRE1, LN-shXBP-1, or LN-Scr tumors. Scale bars: 100 μm.",
    "ncbi_link": "IRE1: 2081
XBP-1: 7494"
  },
  {
    "caption": "XBP-1S mRNA levels in LNCaP xenografts from animals treated with toyocamycin or vehicle. Tumors were harvested, RNA-extracted, and qPCR performed. Error bars indicate SEM. *P = 0.04 for LNCaP and **P = 0.02 for VCaP using unpaired Student's t-test.",
    "ncbi_link": "XBP-1: 7494"
  },
  {
    "caption": "A. FRET-FLIM in live COS-7 cells shows cell surface PlexA-Sema1b cis interaction. Sema1b mutants reveal that both head-to-head and side-on orientations of the PlexA-Sema1b complex are involved in the cis interaction. The cis interaction between Sema1a and PlexA is not observed. The boxcharts represent the average lifetime. Box limits indicate the 25th and 75th percentiles, centred lines show the median, squares represent sample means, whiskers extend 1.5-fold the interquartile range from the 25th and 75th percentiles, p-value was calculated by one-way analysis of variance (ANOVA). *P<0.05, ***P<0.001",
    "ncbi_link": "PlexA: 43832
Sema1b: 37007"
  },
  {
    "caption": "F. Relative change of COS-7 cells surface area upon treatment with Sema1a-Fc. Cells expressing PlexAFL-mClover or PlexAFL-mCover and Sema1b-mRuby2 wild-type or mutants were treated with purified Sema1a-Fc at a final concentration of 5.8 µM. Images were acquired every minute for 30 minutes. Cell surface area was calculated using ImageJ before and after stimulation. Data are presented as means ± sem. *P<0.05, ***P<0.001, p-value calculated by one-way analysis of variance (ANOVA).",
    "ncbi_link": "Sema1b: 37007"
  },
  {
    "caption": "A. Cultured dorsal root ganglion (DRG) neurons from E12.5 Sema6A knockout (KO) embryos were transfected with EGFP, EGFP-tagged wild-type (WT) Sema6A (Sema6A-WT) or different EGFP-tagged Sema6A mutants (Sema6A-mutA, Sema6A-mutB, and Sema6A-mutA+B) at 1 day in vitro (DIV1) and treated with purified Sema6A-Fc at a concentration of 75 nM for 1 hour at 37°C at DIV4. Transfection of EGFP was used as a control (full collapse). DRG neurons from Sema6A KO embryos acquired sensitivity to Sema6A and growth cone collapse was observed in three independent experiments. Transfection of Sema6A-WT, Sema6A-mutA and Sema6A-mutB but not of EGFP or Sema6A-mutantA+B prevented Sema6A-mediated growth cone collapse (Fisher's exact test p<0.0001). Quantification of growth cone collapse was performed using a growth cone morphology matrix (lower part panel A). Data is presented as percentage of morphologically distinct growth cones, divided (represented by the dotted line) in two categories, from uncollapsed (1-4) to fully collapsed (5-8). Totally, 20-40 growth cones were analyzed for each condition per experiment (n=3 experiments). Scale bar 20 µm.",
    "ncbi_link": "EGFP: 
Sema6A: 20358"
  },
  {
    "caption": "A, B. Depletion of Ccdc108   markedly affects bead movement by decreasing  velocity  Fluorescent beads were applied to the dorsal surface of Xenopus embryos. Bead tracks every 500 ms over 2 s are shown (A). Plot of average bead  velocity  shows significantly reduced bead flow in ccdc108  morphants, which can be fully rescued by co-injecting with Xenopus ccdc108 mRNA (B). 150 beads from 15 embryos  for each condition. Arrowheads indicate beads that showed no movement on the embryo  surface through the recording. Data information: Quantification data were collected from three independent experiments. Unpaired two-tailed t-test was performed (*** p<0.001). Mean ± s.d. values are presented.",
    "ncbi_link": "ccdc108: 
Ccdc108: 100144742"
  },
  {
    "caption": "C, D. Defective cilia  formation in ccdc108  morphants. Embryos  at stage 27 were fixed and stained with the acetylated tubulin  (Ac-tub) antibody and/or  Cep164   antibody. mRNA of a membrane-bound form of GFP (mGFP) was co-injected with each morpholino  to indicate targeted cells. Representative  confocal  images (C) and 3D-SIM  images (D) of the epidermis for each condition and plots show significantly reduced cilia number in Ccdc108   depleted embryos. (C) 20 images of 20 embryos and (D) > 80 MCCs from 6 embryos for each condition. Data information: Quantification data were collected from three independent experiments. Unpaired two-tailed t-test was performed (*** p<0.001). Mean ± s.d. values are presented.",
    "ncbi_link": "ccdc108: 
Ccdc108: "
  },
  {
    "caption": "F. Defective cilia  formation occurs in ccdc108 CRISPR  mutants. Embryos  at one cell stage were injected with Cas9 protein with or without the sgRNA against  ccdc108 (108sg) and fixed at stage 27. Representative 3D-SIM images and plot show significantly reduced cilia  number in  ccdc108 CRISPR  mutants. > 70  MCCs  from 6 embryos for each condition. Cell membranes (mGFP, purple), cilia (Ac-tub, green) and basal bodies  (Cep164, yellow) were labeled with indicated antibodies. Data information: Quantification data were collected from three independent experiments. Unpaired two-tailed t-test was performed (*** p<0.001). Mean ± s.d. values are presented.",
    "ncbi_link": "ccdc108: 
CRISPR: "
  },
  {
    "caption": "G.  In situ hybridization chain reaction (HCR) reveals that ccdc108  mRNA is specially detected in  MCCs. Embryos  at stage 35 were fixed and subjected to in situ HCR (red). Embryos were then incubated with the  Ac-tub   antibody (cyan) and DAPI (gray).",
    "ncbi_link": "ccdc108: "
  },
  {
    "caption": "C, D. Representative confocal  images and plots show that  ccdc108 morphants displayed  ciliogenesis defects in neuromasts (C) and olfactory placodes (D). Zebrafish embryos were fixed and stained  with the Ac-tub  antibody (green),  phalloidin (purple) and Hoechst  (blue). Data information: Quantitative data were from three independent repeats. Unpaired two-tailed t-test was performed (*** p<0.001; * p<0.05). Mean ± s.e.m values are presented.",
    "ncbi_link": "ccdc108: 100333283"
  },
  {
    "caption": "E.  Scanning electron microscope images of zebrafish embryos display a failure in cilia  formation in Ccdc108 depleted olfactory placodes.",
    "ncbi_link": "Ccdc108: 100333283"
  },
  {
    "caption": "H. Representative 3D-SIM images and plot reveal that depletion of CCDC108 leads to a significant reduction in multiciliogenesis in mEPCs. mEPCs infected with  lentivirus  expressing indicated shRNA were  serum starved for five days and subjected to immunostaining. GFP-CETN1  (blue) marked mEPCs infected with  lentivirus. Basal bodies (CEP164, purple) and cilia (Ac-tub, green) were labeled with indicated antibodies. > 60 MCCs from three independent repeats for each condition were counted. Data information: Quantitative data were from three independent repeats. Unpaired two-tailed t-test was performed (*** p<0.001; * p<0.05). mean ± s.d. values are presented.",
    "ncbi_link": "CCDC108: 241116"
  },
  {
    "caption": "A. Depletion of  Ccdc108  causes disorganized basal body distribution in MCCs. Representative 3D-SIM images (x-y) and 3D-reconstructions (x-z) of MCCs of embryos  show a failure of apical trafficking of basal bodies  in Ccdc108  depleted cells. Cell membranes (mGFP, blue), basal bodies (Cetn1, green) and distal appendages  (Cep164, purple) were labeled with indicated antibodies. Select area of  Cep164 channel was zoomed to show centriolar Cep164  accumulations. Orange arrowheads and numbers mark individual centriole. > 70 MCCs  from 6 embryos for each condition were counted. Data information: Quantitative data were from three independent experiments. Unpaired two-tailed t-test was performed (*** p<0.001 ; ** p<0.01; * p<0.05). Mean ± s.d. values are presented.",
    "ncbi_link": "Ccdc108: "
  },
  {
    "caption": "B.  Transmission electron microscopy images of Xenopus embryos displaying aberrant apical  trafficking and docking of centrioles in Ccdc108 depleted MCCs. Orange arrowheads mark centrioles. Percentage of  centrioles  docked to plasma membrane  in each field were scored. At least 7 cells for each sample were counted.",
    "ncbi_link": "Ccdc108: "
  },
  {
    "caption": "C. Representative  3D-SIM images reveal that depletion of Ccdc108 has no effect on apical expansion in MCCs. Embryos were fixed and stained with phalloidin (purple). Cilia (Ac-tub, gray) were also presented.  Apical  area of MCCs in each condition were measured ; 80  MCCs from 6 embryos for each condition. D. Representative confocal  images show a significant reduction in apical actin following depletion of    Ccdc108. Cell boundaries and apical actin   network were marked with mGFP (green) and phalloidin (purple) and phalloidin intensity levels measured and plotted. > 80 MCCs from 6 embryos  for each condition. Data information: Quantitative data were from three independent experiments. Unpaired two-tailed t-test was performed (*** p<0.001 ; ** p<0.01; * p<0.05). Mean ± s.d. values are presented.",
    "ncbi_link": "Ccdc108: "
  },
  {
    "caption": "A-C. The IFT-interaction domain is required for Ccdc108 multiciliogenesis function in Xenopus embryos: (A) impaired  multiciliogenesis, (B) defective apical migration/docking of centrioles, and (C) reduced enrichment of apical F-actin. Embryos at stage 27 were fixed and stained with the acetylated tubulin (A; Ac-tub; green), Cep164 (B; purple) and  Cetn1 (B; green) antibodies or phalloidin (purple). mRNA of a membrane-bound form of GFP was co-injected with each morpholino to indicate targeted cells (A,B). Typical D-SIM images (A,B) and confocal  images (C) are present. Embryos were treated as described in Figure 1C and expressed mGFP or  GFP-Ccdc108 mutants. Plots show results from three independent experiments. (A) > 70 MCCs from 6 embryos, and (C) > 70 MCCs from 6  embryos for each condition. Unpaired two-tailed t-test was performed (*** p<0.001; **p<0.01). Mean ± s.d. values are presented.",
    "ncbi_link": "Ccdc108: 
GFP: 
mGFP: 
Ccdc108: 100144742"
  },
  {
    "caption": "A, ift74 CRISPR  mutants display defective cilia formation. Embryos  at  one cell stage were injected and fixed at stage 27 with two independent sgRNA targeting  ift74. Representative confocal images of the  Xenopus epidermis, and plots display defective ciliation. ;60 MCCs from 6  embryos Cell membranes (mGFP), cilia (Ac-tub, green) were labeled with indicated antibodies. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "CRISPR: 
ift74: 734317"
  },
  {
    "caption": "B. ift74 CRISPR  mutants display defective  cilia  formation. Embryos at one cell stage were injected and fixed at stage 27 with two independent sgRNA targeting ift74. Representative  3D-SIM  images of the  Xenopus epidermis, and plots display defective ciliation. ;70 MCCs from 6 embryos for each condition. Cell membranes (mGFP), cilia (Ac-tub, green) and  basal bodies (Cep164) were labeled with indicated antibodies. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "CRISPR: 
ift74: 734317"
  },
  {
    "caption": "C. Ift74  depletion affects centriole apical migration in MCCs. Representative 3D-SIM images (x-y) and 3D-reconstructions (x-z) of MCCs show failure of apical trafficking of basal bodies. Basal bodies (Cetn1, green) and distal appendages  (Cep164, purple) were labeled with indicated antibodies. Quantitative plot shows a slight significant reduction in  basal bodies by the depletion of Ift74. >70  MCCs from 6 embryos for each condition. D. Representative 3D-SIM images and plots reveal that apical  expansion of MCCs is slightly affected by Ift74  depletion. >70 MCCs  from 6 embryos  for each condition. Embryos  were fixed and stained with phalloidin (purple). Cilia (Ac-tub, gray) were also presented. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "Ift74: 734317"
  },
  {
    "caption": "E. Representative confocal  images and plot show a significant reduction in  apical F-actin  enrichment upon Ift74 depletion. >70 MCCs  from 6  embryos for each condition.  Cell boundaries and apical actin network were marked with mGFP (green) and phalloidin (purple). Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "Ift74: 734317"
  },
  {
    "caption": "C-E. Ccdc108 depletion affects  centriolar distribution of IFT-B proteins during  centriole migration in MCCs. Embryos were co-injected with GFP-IFTs (C: Ift74; D:  Ift80; E:  Ift88; green), Cetn4-RFP (purple) and each  morpholino, and imaged at stage 18.  HA  tagged Ccdc108  proteins were co-expressed to test for the rescue of phenotypic defects. Xenopus embryos were subjected to  immunoblotting to evaluate the protein expression levels. α-tubulin (α-Tub) served as loading control. Quantitative plots show that  Ccdc108-depleted MCCs showed a significant decrease of centriolar  distribution of IFT-B proteins (Ift74, Ift80 and Ift88), and Ccdc108-IFT  interaction deficient mutants are unable to rescue the decreased centriolar accumulation of IFT-B proteins. >40 MCCs from 6 embryos for each condition. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001). Mean ± s.d. values are also presented.",
    "ncbi_link": "Ccdc108: 
GFP: 
Ift74: 734317
Ift80: 394395
Ift88: 8100"
  },
  {
    "caption": "A, B. Centriolar distribution of ciliary adhesion complex related proteins  Fak and Cp110  are not reduced following Ccdc108  depletion.  Embryos  were co-injected with GFP-Cp110 (A) GFP-Fak (B),  Cetn4-RFP (purple) and each morpholino, and imaged at stage 18. >30  MCCs from 6 embryos  for each condition. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "Ccdc108: 
GFP: 
Cp110: 108701549
Fak: 432072"
  },
  {
    "caption": "C, D.  Ccdc108   depletion affects  centriolar distribution of PCP associated actin cytoskeleton regulators important for centriole migration in MCCs. Embryos were co-injected with GFP-Drg1 (C) GFP-RBD (D), Cetn4-RFP (purple) and each morpholino, and imaged at stage 18.  HA tagged Ccdc108 proteins were co-expressed to test for the rescue of phenotypic defects. Xenopus embryos  were subjected to immunoblotting to evaluate the protein expression  levels.  α-tubulin (α-Tub) served as loading control. Quantitative plots show that Ccdc108-depleted MCCs showed a significant decrease of  centriolar  distribution of Drg1 and  RBD, and neither of Ccdc108-IFT interaction deficient mutants can rescue the  centriolar phenotypic defects. >30 MCCs  from 6 embryos for each condition. Data information: Quantitative data from three independent experiments were scored. Unpaired two-tailed t-test was performed (*** p<0.001; ** p<0.01). Mean ± s.d. values are also presented.",
    "ncbi_link": "Ccdc108: 
GFP: 
RBD: 
Drg1: 399253"
  },
  {
    "caption": "I. EATR assay. Chondrocytes with indicated genotypes (ctrl=wild type) treated with FGF18 (50 ng/mL; 16 hours) where indicated. ER acidification was measured by FACS. Mean +/- standard error of the mean (sem) of N= 17 (veh), N=17 (FGF18), N=4 (FGFR3;4KO); N=4 (FGFR3;4KO FGF18) biological replicates. Analysis of variance one way (ANOVA) p<0.0001; Tukey's post hoc test ***p<0.0005; NS not significant.",
    "ncbi_link": "FGFR3: 84489"
  },
  {
    "caption": "E. Co-immunofluorescence of p-IRS1 S307 mouse (green) and p-S6 S240/S242 (red) ribosomal protein in IRS1-overexpressing RCS chondrocytes treated with FGF18 (50 ng/mL) for 12h. Nuclei (N) were stained with DAPI (blue). Scale bar 15 μm. Quantification analysis of p-S6 fluorescence intensity in IRS1-overexpressing vs non expressing RCS chondrocytes. Mean +/- standard error of the mean (sem) of N=3 biological replicates. n=35 cells analyzed. Student's paired T-test *p<0.05.",
    "ncbi_link": "IRS1: 16367"
  },
  {
    "caption": "E. qRT-PCR analysis of ER-phagy receptors in RCS chondrocytes. Gene expression was analyzed after FGF18 (50 ng/mL) treatment for 16 hours. Fold change values were relative to vehicle (5% ABS) and normalized to Cyclophilin gene. Mean +/- standard error of the mean (sem) of N=3 biological replicates/treatment. Student's paired T-test **p<0.005; *p<0.05.",
    "ncbi_link": "Cyclophilin: "
  },
  {
    "caption": "F. (top) Representative model of Fam134b∆LIR protein. LIR= LC3-Interacting-Region. (bottom) Western blot analysis of Fam134b in chondrocytes with indicated genotypes (ctrl=wild type) treated with FGF18 (50 ng/mL) for 16 hours. Representative images of N=3 biological replicates/treatment. β-actin was used as loading control. Bar graph showed quantification of Fam134b band intensity normalized to β-actin. Mean +/- standard error of the mean (sem). Student's paired T-test, *p<0.05.",
    "ncbi_link": "Fam134b: 619558"
  },
  {
    "caption": "B. Western blot analysis of TFEB, and phospo-TFEB (Serine 142) in RCS chondrocytes stably expressing human TFEB-3XFlag protein. Cells were treated with vehicle (5% ABS) or FGF18 (50 ng/mL) for 16h. β-actin was used as loading control. Representative of three independent experiments.",
    "ncbi_link": "Flag: 
TFEB: 7942"
  },
  {
    "caption": "C. GFP immuno-EM staining in FGFR3/4KO chondrocytes infected with a constitutive nuclear (and active) mutant TFEB fused to GFP tag (TFEB- S142A:S211A-GFP). GFP positive gold immune-particles showed presence of GFP-puncta into the nucleus (N, stained in green for visualization). Lysosomes were stained in blue for visualization. Insets showed magnification of lysosomes. Quantification of lysosome diameter (nm) in control (wild type) and FGFR3;4KO chondrocytes infected with empty or with TFEB- S142A:S211A-GFP vector. Mean +/- standard error of the mean (sem) of N=3 biological replicates. n=40 (veh) n=78 (FGFR3;4KO) n=57 (FGFR3;4KO +TFEB-S142A:S211A-GFP) cells were analyzed. Scale bar 500 nm. Kruskal Wallis test p=1.43e-13; Nemenyi post hoc test ***p<0.0005; NS not significant.",
    "ncbi_link": "GFP: 
FGFR3: 84489
TFEB: 7942"
  },
  {
    "caption": "D. Co-immunofluorescence of p-IRS1 (S307 mouse) and TFEB in IRS1-overexpressing RCS chondrocytes treated with FGF18 (50 ng/mL) for 12h. Nuclei (N) were stained with DAPI (blue) and delimited with dashed line. Scale bar 15 μm. Quantification of TFEB nuclear localization in IRS1-overexpressing vs non-expressing RCS. Mean +/- standard error of the mean (sem) of N=3 biological replicates. n= 124 cells analyzed; Student's un-paired T-test *p<0.05.",
    "ncbi_link": "IRS1: 16367"
  },
  {
    "caption": "A. qRT-PCR analysis of Fam134b gene expression in chondrocytes with indicated genotypes (ctrl=wild type) treated with vehicle (5% ABS) or with FGF18 (50 ng/mL; 16 hours). Fold change values were relative to vehicle and normalized to Cyclophilin gene. Mean +/- standard error of the mean (sem) of N=3 biological replicates. Analysis of variance one way (ANOVA) p<0.0001: Tukey's post hoc test ***p<0.0005; NS not significant.",
    "ncbi_link": "Cyclophilin: 
Fam134b: 619558"
  },
  {
    "caption": "C. Co-staining of CLIMP63 (green) and TMEM192-HA (lysosomes, red) in control and TFEB;3KO RCS treated with FGF18 (50 ng/mL for 16 hours). BaFA1 was used at 100 nM for 3h. Scale bar 15 μm and 2 μm (higher magnification boxes).",
    "ncbi_link": "TFEB: 316214"
  },
  {
    "caption": "F,G Data plots show quantification of mCherry+ vesicles/cell (autolysosomes) (F) and mCherry+/GFP+ vesicles/cell (autophagosomes) (G) in wild type (ctrl) and TFEB;3KO cells treated with vehicle (veh) or FGF18. N=3 independent experiments. Mean +/- standard error of the mean (sem) of N=24 (wild type treated with 5%ABS, veh), N=30 (wild type treated with FGF18), N=27 (TFEB;3KO veh), N= 33 (TFEB;3KO FGF18) cells. Student un-paired T-Test ***p<0.0005; **p<0.005.",
    "ncbi_link": "TFEB: 316214"
  },
  {
    "caption": "H. ChIP analysis of TFEB binding to Fam134b DNA in RCS cells transfected with TFEB-3XFLAG. Numbers in the CLEAR site (yellow box) refer to the distance [in base pairs] from the transcriptional start site (+1) of Fam134b-2 gene. Immunoprecipitated DNA was normalized to the input and plotted as relative enrichment over a mock control. Bar graph shows fold change enrichment; mean +/- standard error of the mean (sem) of N=3 independent experiments. Student un-paired T-Test **p<0.005.",
    "ncbi_link": "FLAG: 
Fam134b: 619558
TFEB: 7942"
  },
  {
    "caption": "I-J. Luciferase assays in RCS chondrocytes using as promoter a 0,7kb genomic Fam134b DNA fragment containing a wild type (FAM134B-WT) or a deleted (FAM134B-mut) version of the CLEAR site. TFEB plasmid transfection amount and FGF18 (50 ng/mL for 16h) treatments are indicated. Mean +/- standard error of the mean (sem) of N=3 biological replicates. Student paired T-test *p<0.05; **p<0.005.",
    "ncbi_link": "Fam134b: 619558
FAM134B: 619558
TFEB: 7942"
  },
  {
    "caption": "K. Luciferase activity in wild type (ctrl) and TFEB;3KO RCS chondrocytes with indicated genotypes expressing the indicated Fam134b luciferase report plasmids and treated with FGF18 overnight (50 ng/mL) where indicated. Mean +/- standard error of the mean (sem) of N=5 biological replicates. Analysis of variance one way (ANOVA) p<0.0001: Sidak's multiple comparison test ***p<0.0005; NS not significant.",
    "ncbi_link": "Fam134b: 619558
TFEB: 316214"
  },
  {
    "caption": "A. qRT-PCR analysis of Fam134b isoforms in mock, TFEB S142A:S211A and TFE3 S246A:S312A over-expressing U2OS cells. Values were normalized to Hprt gene and expressed as fold change values relative to mock. Mean +/- standard error of the mean (sem) of N=3 biological replicates. Student's un-paired T-test *p<0.05; NS not significant.",
    "ncbi_link": "Hprt: 3251
Fam134b: 54463
TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "B. Western blot analysis of Fam134b isoforms in mock, TFEB S142A:S211A and TFE3 S246A:S312A over-expressing U2OS cells showing induction of FAM134B-2, but not of FAM134B-1 isoform by TFEB/TFE3. Filamin A was used as loading control. Blot is representative of N=3 independent experiments.",
    "ncbi_link": "TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "C,D. Co-immunofluorescence staining of ER (CLIMP-63, green) and lysosomes (TMEM192-HA, red) in control and Sh-FAM134B U2OS cells over-expressing TFEB S142A:S211A-GFP (purple). BaFA1 was used at 100 nM for 4h. Scale bar 15 μm and 2 μm (higher magnification boxes) (C). In (D), Quantification of CLIMP63 fluorescence in TMEM192-HA decorated lysosomes. Mean +/- standard error of the mean (sem) of N=3 biological replicates. N= 21 (vehicle ctrl), N=33 (TFEB S142A:S211A-GFP ctrl), N=21 (vehicle shFAM134B), N= 30 (TFEB S142A:S211A-GFP shFAM134B) cells were analysed. Student's un-paired T-test ***p<0.0005; NS not significant.",
    "ncbi_link": "GFP: 
FAM134B: 54463
TFEB: 7942"
  },
  {
    "caption": "E,F. Co-immunofluorescence staining of ER (CLIMP-63, green) and lysosomes (Lamp1, red) in WT and Fam134bKO MEF cells over-expressing TFEB S142A:S211A-GFP (purple). BaFA1 was used at 100 nM for 4h. Scale bar 15 μm and 2 μm (higher magnification boxes) (E). In (F), Quantification of CLIMP63 fluorescence in Lamp1 decorated lysosomes. Mean +/- standard error of the mean (sem) of N=3 biological replicates. N= 20 (vehicle ctrl), N=22 (TFEB S142A:S211A-GFP ctrl), N=21 (vehicle Fam134bKO), N= 20 (TFEB S142A:S211A-GFP Fam134bKO) cells were analysed. Student's un-paired T-test ***p<0.0005; NS not significant.",
    "ncbi_link": "GFP: 
Fam134b: 66270
TFEB: 7942"
  },
  {
    "caption": "A,B. Representative images of alcian blue (cartilage) and Alizarin red (bone) skeletal staining showing growth retardation in Fgfr3/4 dKO mice compared to age/sex wild type littermate at post-natal day 30. B. Femur, tibia and tail details.",
    "ncbi_link": "Fgfr3: 14184"
  },
  {
    "caption": "C. Haematoxylin/Eosin staining of femoral growth plate sections from wild type and Fgfr3/4 dKO mice. Higher magnification insets showed a disorganized hypertrophic chondrocyte layer, in Fgfr3/4 dKO mice. Scale bar 60 μm.",
    "ncbi_link": "Fgfr3: 14184"
  },
  {
    "caption": "F. qRT-PCR analysis of Fam134b-2 expression from growth plate of mice with indicated genotypes. N=8 (wt mice) and N=9 (Fgfr3/4 dKO mice) were analyzed. Values were normalized to Hprt gene and expressed as fold change relative to control. Mean +/- standard error of the mean (sem). Student's un-paired T-test *p<0.05.",
    "ncbi_link": "Fgfr3: 14184
Hprt: 15452
Fam134b-2: 66270"
  },
  {
    "caption": "G. Western blot analysis of Fam134b-2 protein from growth plate lysates of mice with indicated genotypes. β-actin was used as loading control. N=6 (wt mice) and N=4 (Fgfr3/4 dKO mice) were analyzed. Bar graph showed quantification of Fam134b-2 normalized to β-actin. Mean +/- standard error of the mean (sem). Student's un-paired T-test *p<0.05.",
    "ncbi_link": "Fgfr3: 14184"
  },
  {
    "caption": "H. Representative immunofluorescence staining of CLIMP-63 of femur growth plate sections from mice with indicated genotypes. Scale bar 10μm. Insets showed increased CLIMP-63 staining in Fgfr3/4 dKO mice. Scale bar 5 μm. Hypert= hypertrophic chondrocytes; pre-hypert= pre-hypertrophic chondrocytes; prolif = proliferating chondrocytes.",
    "ncbi_link": "Fgfr3: 14184"
  },
  {
    "caption": "A. Scatter plot of cellular compartments and biological processes regulated by FGF18 in a Fam134b-dependent manner. Score: Student's T-test difference between wild type and Fam134b∆LIR cells. N=3 biological replicates/treatment/genotype were analysed. FDR <0.05.",
    "ncbi_link": "Fam134b: 66270"
  },
  {
    "caption": "B. Tandem mass tag secretome analysis of chondrocytes with indicated genotypes and treatments. Fam134b-dependent secreted proteins are shown N=3 biological replicates/treatment/genotype were analysed. FDR <0.05.",
    "ncbi_link": "Fam134b: 66270"
  },
  {
    "caption": "C. qRT-PCR analysis of Fam134b and Lamp1 from medaka fish embryos treated with FGF18 (50 ng/mL) for 24h. Values were normalized to Hprt gene and expressed as fold change relative to untreated fish. N= 5 biological replicates. Mean +/- standard error of the mean (sem). Paired Student's T-test **p<0.005; *p<0.05.",
    "ncbi_link": "Hprt: 
Lamp1: 101175550
Fam134b: 101158885"
  },
  {
    "caption": "F. Western blot analysis of type II procollagen from a pool of medaka fish embryos with indicated genotypes, showing procollagen accumulation in Fam134bmo fish. β-actin was used as loading control. Bar graph shows quantification of type II procollagen normalized to β-actin. N=3 biological replicates. Mean +/- standard error of the mean (sem). Student's un-paired T-test *p<0.05.",
    "ncbi_link": "Fam134b: 101158885"
  },
  {
    "caption": "G. Representative TEM images of medaka fish chondrocytes. Arrows indicated the ER. Insets show ER enlargement in Fam134bmo chondrocyte. N=3 fish/genotype were analyzed. Bar graph shows number of ER enlargement per cell in medaka fish with indicated genotypes. N=29 cells (Fam134bwt) and N=37 cells (Fam134bmo) were analyzed. Mean +/- standard error of the mean (sem). Student's un-paired T-test ***p<0.0005. Scale bar 500 nm. N=nucleus, ER= Endoplasmic Reticulum.",
    "ncbi_link": "Fam134b: 101158885"
  },
  {
    "caption": "H. Lateral (top) and ventral (bottom) projections of medaka fish embryos with indicated genotypes. Scale bar 1mm. Bar graphs show quantification of total length and head size of medaka fish model of Fam134bmo expressed as % relative to the scramble. Mean +/- standard error of the mean (sem) of at least n=8 fish/genotype. Student un-paired T-Test *p<0.05.",
    "ncbi_link": "Fam134b: 101158885"
  },
  {
    "caption": "Alcian blue (cartilage) (I) staining of scramble and Fam134bmo medaka fish. Graph shows quantification of Ethmoid plate (EP), Palatoquadrate (PQ), Ceratohyal (CH), Paired Prootics (PO), Ceretobranchials 1 to 5 (CB1 to CB5) cartilage length (I) in Fam134bmo and scramble fish. Values were expressed as % relative to the scramble (100% red dotted line). Mean +/- standard error of the mean (sem) of n=9 fish/genotype. Student unpaired T-Test *p<0.05; **p<0.005; ***p<0.0005. NS not significant.",
    "ncbi_link": "Fam134b: 101158885"
  },
  {
    "caption": "Alizarin Red (bone) (J) staining of scramble and Fam134bmo medaka fish. Graph shows quantification of Ethmoid plate (EP), Palatoquadrate (PQ), Ceratohyal (CH), Paired Prootics (PO), Ceretobranchials 1 to 5 (CB1 to CB5) bone mineralization (J) in Fam134bmo and scramble fish. Values were expressed as % relative to the scramble (100% red dotted line). Mean +/- standard error of the mean (sem) of n=9 fish/genotype. Student unpaired T-Test *p<0.05; **p<0.005; ***p<0.0005. NS not significant.",
    "ncbi_link": "Fam134b: 101158885"
  },
  {
    "caption": " (A) Bcl-xfl/fl;RosaCreERT2+/Ki (n=12) or, as controls, Bcl-xfl/fl (n=6) and RosaCreERT2+/Ki (n=16) mice (age 9-12 weeks, males and females) were treated with tamoxifen (200 mg/kg/body weight administered in 3 daily doses by oral gavage) to induce CreERT2-mediated deletion of the floxed Bcl-x alleles. Mice were monitored for up to 200 days post-treatment with tamoxifen. Data are presented as % survival post-treatment with tamoxifen and statistical significance was assessed using the Mantel-Cox (Log-rank) test; ****p<0.0001. ",
    "ncbi_link": "Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (B) Bcl-xfl/fl;RosaCreERT2+/Ki (n=24) or, as controls, Bcl-xfl/fl (n=9) and RosaCreERT2+/Ki (n=6) mice (males and females, aged 8-14 weeks, numbers also indicated in the figure legend) were lethally γ-irradiated (2 x 5.5 Gy, 3 h apart) and reconstituted with bone marrow from UBC-GFP mice (referred to as GFP-Chimeras). After 8 weeks, reconstituted mice were treated with tamoxifen (200 mg/kg body weight administered in 3 daily doses oral gavage) and monitored for up to 200 days (termination of the experiment). Data are presented as % survival post-treatment with tamoxifen and statistical significance was assessed using the Mantel-Cox (Log-rank) test; ****p<0.0001. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417
UBC: 22190"
  },
  {
    "caption": " (C-F) Total counts of (C) platelets, (D) red blood cells (RBC), (E) hemoglobin (HGB) content and (F) hematocrit (HCT) of tamoxifen-treated Bcl-xfl/fl;RosaCreERT2+/Ki (n=8) or, as controls, Bcl-xfl/fl (n=6) and RosaCreERT2+/Ki (n=12) and Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimera (n=21) or, as controls, Bcl-xfl/fl;GFP-Chimera (n=6) and RosaCreERT2+/Ki;GFP-Chimera (n=6) mice were determined by ADVIA. Data are presented as mean ±SEM. Each data point represents an individual mouse. Statistical significance was assessed using the Student's t-test; ****p<0.0001. (G) Spleen weights were measured in sick mice (at sacrifice) or, for the healthy control mice, at the termination of the experiment. Data are presented as mean ±SEM. Each data point represents an individual mouse and numbers are indicated. Statistical significance was assessed using the Student's t-test; ****p<0.0001. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (H) Representative image of enlarged spleens from two Bcl-xfl/fl;RosaCreERT2Ki/+ mice and age-matched control Bcl-xfl/fl and RosaCreERT2+/Ki mice (34 days after treatment). ",
    "ncbi_link": "Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": "Bcl-xfl/fl;RosaCreERT2+/Ki (n=8) or, as controls, Bcl-xfl/fl (n=6) and RosaCreERT2+/Ki (n=12) mice as well as Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=21), or as controls, Bcl-xfl/fl;GFP-Chimeras (n=6) and RosaCreERT2+/Ki;GFP-Chimeras (n=6) (age 8-14 weeks, males and females) were treated with tamoxifen (200 mg/kg/body weight administered in 3 daily doses by oral gavage) to induce CreERT2-mediated deletion of the floxed Bcl-x alleles. (A) Total white blood cell counts (WBC) were analyzed by ADVIA in sick mice or at the termination of the experiment (healthy control mice). Data are presented as mean ±SEM. Each data point represents an individual mouse and n numbers are indicated above. Statistical significance was assessed using the Student's t-test. No statistically significant differences were observed. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (B) The neutrophil/lymphocyte ratio (NLR) is presented as mean ±SEM for sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=21) or healthy control RosaCreERT2+/Ki;GFP-Chimeras (n=6) at the termination of the experiment. Data are presented as mean ±SEM. Each data point represents an individual mouse. Statistical significance was assessed using the Student's t-test; *p<0.05. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (C) Histological analysis of H&E-stained sections of the sternum of sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras or healthy wild-type and RosaCreERT2+/Ki;GFP-Chimera control mice at the indicated time points post-treatment with tamoxifen (dpt=days post-treatment). ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (D) Histological analysis of H&E-stained sections of the livers of sick mice or age-matched healthy control wild-type mice or healthy RosaCreERT2+/Ki;GFP-Chimeras at the termination of the experiment (dpt=days post-treatment). ",
    "ncbi_link": "Rosa: 
GFP: 
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (E) ALT (left panel), AST (middle panel) and bilirubin levels (right panel) in the serum were determined in sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=18) or in healthy RosaCreERT2+/Ki;GFP-Chimeras (n=4) at the termination of the experiment. Data are presented as mean ±SEM. Each data point represents one individual mouse. Statistical significance was assessed using Student's t-test; **p<0.01. nd=not detected. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " Bcl-xfl/fl;RosaCreERT2+/Ki (n=7) or as controls, Bcl-xfl/fl (n=8) and RosaCreERT2+/Ki (n=16) mice as well as Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=5), Bcl-xfl/fl;GFP-Chimeras (n=8) and RosaCreERT2+/Ki;GFP-Chimeras (n=6) (age 8-14 weeks, males and females) were treated with tamoxifen (200 mg/kg/body weight administered in 3 daily doses by oral gavage) to induce CreERT2-mediated deletion of the floxed Bcl-x alleles. (A) Kidney weights were measured in sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (at sacrifice) or, for the healthy control mice, at the termination of the experiment. Data are presented as mean ±SEM. Each data point represents one individual mouse. Statistical significance was assessed using Student's t-test; *p<0.05, ***p<0.001. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (B) Picture showing both kidneys from age-matched healthy control wild-type mice (left) and sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (right). ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (C) Histological analysis of H&E-stained sections of the kidneys of age-matched healthy control mice or sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras as indicated, showing from left to right, shrunken scarred kidney, segmental chronic tubulo-interstitial disease, accumulation of cellular debris and amorphous material within the collecting ducts of the papilla. The higher magnification shows tubular epithelial degeneration, apoptosis and segmental secondary glomerular sclerosis. Pictures are representative of at least 5 mice for each genotype and treatment. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (D) Multiphoton analysis of fixed sections of the kidneys of age-matched healthy RosaCreERT2+/Ki;GFP-Chimeras (left) or sick Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (right). Pictures are representative of at least 3 mice for each genotype and treatment. green=second harmony, blue=short wavelength autofluorescence. ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (A) TUNEL staining of kidney sections from control RosaCreERT2+/Ki, Bcl-xfl/fl;RosaCreERT2+/Ki, RosaCreERT2+/Ki;GFP-Chimeras or Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras at the indicated time points post-tamoxifen treatment (200 mg/kg/body weight administered in 3 daily doses by oral gavage) or γ-irradiation (2 x 550 Rad), as indicated. Slides were counterstained with hematoxylin. Arrow heads indicate examples of TUNEL+ (apoptotic) cells. (B) TUNEL+ cells were quantified using a personalized script for the Image J software. Kidney sections were divided into ~40 microscopic images and the total numbers of blue and brown (TUNEL+) nuclei were determined. The percentages of TUNEL+ nuclei were calculated for each picture. The average value for each kidney section was then determined and plotted as a single data point. Error bars represent SEM from at least 3 independent samples for each genotype and treatment. Statistical significance was assessed using one-way ANOVA analysis with Tukey's multiple comparisons test (comparing control RosaCreERT2+/Ki (24 h post-tamoxifen n=2, 24 h post-γ-irradiation n=9) with Bcl-xfl/fl;RosaCreERT2+/Ki (24 h post-tamoxifen n=6, 24 h post-γ-irradiation n=5) and control RosaCreERT2+/Ki;GFP-Chimeras (24 h post-tamoxifen n=7, End point n=8) with Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (24 h post-tamoxifen n=8, End point n=6) (***p<0.001). ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Cre: 2777477
ERT2: 26417"
  },
  {
    "caption": " (A, B) Data are presented as % survival and statistical significance was assessed using the Mantel-Cox (Log-rank) test comparing tamoxifen-treated Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=25) with Bcl-xfl/fl;RosaCreERT2+/Ki;Bim+/-;GFP-Chimeras (n=25), Bcl-xfl/fl;RosaCreERT2+/Ki;Bim-/-;GFP-Chimeras (n=18), Bcl-xfl/fl;RosaCreERT2+/Ki;Puma+/-;GFP-Chimeras (n=21), Bcl-xfl/fl;RosaCreERT2+/Ki;Puma-/-;GFP-Chimeras (n=15) and Bcl-xfl/fl;RosaCreERT2+/Ki; Bim+/-;Puma+/-;GFP-Chimeras (n=22). *p<0.05, ****p<0.0001. The survival curves for the Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Bim: 12125
Cre: 2777477
Puma: 80885
ERT2: 26417"
  },
  {
    "caption": " (D-F) (D) Total red blood cell (RBC) count, (E) hematocrit (HCT) and (F) hemoglobin (HGB) content were determined by ADVIA in the blood of sick mice of the indicated genotypes or at the termination of the experiment for healthy controls. Data are presented as mean ±SEM. Each data point represents one individual mouse. Statistical significance was assessed using Student's t-test comparing tamoxifen-treated RosaCreERT2+/Ki;GFP-Chimeras (n=6) with Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras (n=21), Bcl-xfl/fl;RosaCreERT2+/Ki;Bim+/-;GFP-Chimeras (n=20), Bcl-xfl/fl;RosaCreERT2+/Ki;Bim-/-;GFP-Chimeras (n=12), Bcl-xfl/fl;RosaCreERT2+/Ki;Puma+/-;GFP-Chimeras (n=15), Bcl-xfl/fl;RosaCreERT2+/Ki;Puma-/-;GFP-Chimeras (n=10) and Bcl-xfl/fl;RosaCreERT2+/Ki; Bim+/-;Puma+/-;GFP-Chimeras (n=17) ; ***p<0.001; ****p<0.0001. Data for the Bcl-xfl/fl;RosaCreERT2+/Ki;GFP-Chimeras and RosaCreERT2+/Ki;GFP-Chimeras ",
    "ncbi_link": "GFP: 
Rosa: 
Bcl-x: 12048
Bim: 12125
Cre: 2777477
Puma: 80885
ERT2: 26417"
  },
  {
    "caption": " (A) GFP-Chimeras were treated with the BCL-XL inhibitor A1331852 (n=8, 5 doses by oral gavage, 25 mg/kg body weight each dose). Control groups (n=8 each group) include untreated GFP-Chimeras and un-irradiated C57BL/6-Ly5.1 (wild-type) mice treated with the BCL-XL inhibitor A1331852 or left untreated. Mice were monitored for up to 200 days post-treatment (dpt). Data are presented as % survival. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " Total red blood cell count (RBC), platelet count, hemoglobin (HGB) content and hematocrit (HCT) were determined by ADVIA as indicated in the blood of drug-treated GFP-Chimeras or control mice (n=8 each group) at the termination of the experiment Data are presented as mean ±SEM. Each data point represents one individual mouse. Statistical significance was assessed using one-way ANOVA analysis with Tukey's multiple comparisons test comparing untreated and drug-treated mice within each group (*p<0.05, **p<0.01, ***p<0.001, ****p>0.0001). ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " (A) GFP-Chimeras were treated with the BCL-XL inhibitor A1331852 (n=8, 5 doses by oral gavage, 25 mg/kg body weight each dose). Control groups (n=8 each group) include untreated GFP-Chimera and un-irradiated C57BL/6-Ly5.1 (wild-type) mice treated with the BCL-XL inhibitor A1331852 or left untreated. Kidney (left panel) and spleen weights (right panel) were measured in drug-treated GFP-Chimeras or control mice at the termination of the experiment (n=8 each group). Data are presented as mean ±SEM. Each data point represents one individual mouse. Statistical significance was assessed using one-way ANOVA analysis with Tukey's multiple comparisons test. No statistically significant differences were observed. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " (C) Histological analysis of H&E-stained sections of the kidneys of drug-treated GFP-Chimeras or control mice at the termination of the experiment. Pictures are representative of at least 3 mice for each treatment group. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B Fluorescence images of cells expressing GPD promoter-driven GFP-Pho8 and the ER marker Sec63-mCherry and stained with CMAC to label the vacuole. The upper and lower panel show vacuole-associated and perinuclear GFP-Pho8 stretches and an intravacuolar GFP-Pho8 ring, respectively. Scale bars: 2 µm.",
    "ncbi_link": "GPD: 853106"
  },
  {
    "caption": "C Correlative light and electron microscopy of cells expressing GPD promoter-driven GFP-Pho8 and Sec63-mCherry. The lower panel shows the boxed area in the electron micrograph at higher magnification. The ER ring corresponds to a vacuolar whorl and the ER stretch to a perinuclear stack.",
    "ncbi_link": "GPD: 853106"
  },
  {
    "caption": "A Individual frames from time-lapse imaging of a cell expressing GAL promoter-driven GFP-Pho8 and stained with the vacuole membrane dye FM4-64. Numbers indicate the time in minutes after the start of the image sequence. Scale bar: 2 µm.",
    "ncbi_link": "GAL: 852308"
  },
  {
    "caption": "B Electron micrograph of a cell expressing GPD promoter-driven GFP-Pho8. Arrows indicate the edges of ER cisternae that are part of a bent stack in a vacuole membrane invagination. Black arrowheads point to vacuole membrane that encases the bent stack and the whorl.",
    "ncbi_link": "GPD: 853106"
  },
  {
    "caption": "Fluorescence images of ∆atg7 and ∆atg8 cells (A) expressing GAL promoter-driven GFP-Pho8 and the ER marker Sec63-mCherry and stained with CMAC to label the vacuole. Scale bar: 2 µm.",
    "ncbi_link": "atg7: 856576
atg8: 852200
GAL: 852308"
  },
  {
    "caption": "Fluorescence images of ∆snf7 and ∆vps4 cells (B) expressing GAL promoter-driven GFP-Pho8 and the ER marker Sec63-mCherry and stained with CMAC to label the vacuole. Scale bar: 2 µm.",
    "ncbi_link": "GAL: 852308
snf7: 850712
vps4: 856303"
  },
  {
    "caption": "C Relative activity of the ER-phagy reporter Yop1-Pho8∆60 in tunicamycin-treated cells. The dotted line indicates the activity in ∆atg7 cells. Mean + SEM, n ≥ 3.",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "D, E Relative activity of endogenous Pho8 in untreated cells (D) or after tunicamycin treatment (E). Background activity determined in ∆pho8 mutants was subtracted from the activity in all other strains. Mean + SEM, n = 3. WT, wild-type.",
    "ncbi_link": "pho8: 852092"
  },
  {
    "caption": "F, G Growth assays of untreated and tunicamycin-treated WT, ∆atg39/40, ∆snf7 and ∆snf7 ∆atg39/40 cells. Numbers indicate growth relative to WT cells based on the areas under the curves. Mean ± SEM, n = 3.",
    "ncbi_link": "atg39: 851021
snf7: 850712"
  },
  {
    "caption": "A Fraction of wild-type (WT), ∆vps23, ∆snf7 and ∆vps4 cells with GFP-Pho8 structures. Mean + SEM, n ≥ 3.",
    "ncbi_link": "snf7: 850712
vps23: 850349
vps4: 856303"
  },
  {
    "caption": "B Fraction of GFP-Pho8 structures classified as stacks, cytosolic whorls, uptake intermediates or vacuolar whorls. The number of GFP-Pho8 structures in WT, ∆vps23, ∆snf7 and ∆vps4 cells was 562, 345, 367 and 449, respectively. The table shows the results of Chi-Square tests for independence for all pairs of strains. ***, highly significant (P < 0.00001); ns, not significant (P > 0.05).",
    "ncbi_link": "snf7: 850712
vps23: 850349
vps4: 856303"
  },
  {
    "caption": "C Fraction of stacks classified as peripheral, perinuclear or vacuole-associated. The number of stacks in WT and ∆snf7 cells was 252 and 351, respectively. The observed distributions in the two strains were analyzed with a Chi-Square test for independence. ***, highly significant (P < 0.00001).",
    "ncbi_link": "snf7: 850712"
  },
  {
    "caption": "A Electron micrographs of wild-type and ∆snf7 cells treated with DTT for 3 h. Cy, cytosol; V, vacuole. Scale bars: 300 nm.",
    "ncbi_link": "snf7: 850712"
  },
  {
    "caption": "C, D Electron micrographs of serial thin sections of a ∆snf7 cell (C) or a wild-type cell (D) treated with DTT for 3 h. Note that the whorl appears separated from the cytosol in some sections (e.g. section 300 nm) but is still in contact with the cytosol (see sections 600 nm and 700 nm). In the wild-type cell (D), the vacuolar whorl is completely separated from the cytosol. Scale bar: 300 nm.",
    "ncbi_link": "snf7: 850712"
  },
  {
    "caption": "(C, D) qRT-PCR  analysis of Il2  and Ifng  mRNA in  CD4+ T cells from LN  and OB mice (C) or from  aged lean (AL, 17-month-old) and aged obese  (AO, 17-month-old) mice (D), then stimulated with TCR  (1/1 μg/ml) for 6 h. For AL  and AO mice, mice  were fed with a  normal diet  for 17 months, then divided into AL  (≤ 35 g) and AO  (≥ 45 g) mice  based on body weight (n = 3 or 4, biological replicates). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "ncbi_link": "Ifng: 15978
Il2: 16183"
  },
  {
    "caption": "(S) BM12/SJL mice  (recipient, R) were adoptively transferred with CD4+ T cells from WT and Cpt1a-KO lean  or obese mice  (donors, D) to induce inflammation. The anti-nuclear  antibody (ANA) in serum  (top, scale bar: 50 μm) and the kidney IgG  deposition (bottom, scale bar: 50 μm) were visualized using immunofluorescence  (n = 4 or 5, biological replicates). Data are presented as Immunofluorescent  images (left) and quantification bar graphs (right). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "ncbi_link": "Cpt1a: 12894"
  },
  {
    "caption": "(R) Endogenous ubiquitination  of Usp9x  in WT and Goliath-deficient CD4+ T cells that were left unstimulated  (-) or stimulated  (+) with α-CD3/28 (5/5 μg/ml).",
    "ncbi_link": "Goliath: 59044"
  },
  {
    "caption": "(S) Co-IP  analysis of the interactions  between CaN  and Usp9x  or NFATc2  and CaN  in WT and Goliath-KO CD4+ T cells that were left unstimulated  (-) or stimulated  (+) with α-CD3/28 (5/5 μg/ml).",
    "ncbi_link": "Goliath: 59044"
  },
  {
    "caption": "(A, B) Immunoblot  analysis of cytoplasmic  and nuclear  NF-AT levels in WT and Goliath-KO naïve  CD4+ T cells from lean  (LN) or obese  (OB) mice  that were stimulated by α-CD3/28 (5/5 μg/ml) or PMA/ionomycin  (P/I, 10/100 ng/ml).",
    "ncbi_link": "Goliath: 59044"
  },
  {
    "caption": "(C-F) ECAR  measurements of glycolysis in WT and Goliath-deficient  naïve  CD4+ T cells treated with DMSO or fenofibrate  (FF, 5 μM) (C, D), or isolated from LN  or OB mice (E, F) that stimulated by α-CD3/28  (1/1 μg/ml) for 24 h (n = 3, biological replicates). The statistical results are presented as bar graphs (D, F). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "ncbi_link": "Goliath: 59044"
  },
  {
    "caption": "(J-L) BM12/SJL mice  (recipient, R) were adoptively transferred with  CD4+ T cells from WT and Goliath-KO lean  or obese mice  (donors, D) to induce inflammation. The anti-dsDNA, anti-ssDNA  and anti-histone IgG  or IgM  in serum  were examined by ELISA (J). ANA in serum  (top, scale bar: 50 μm) and the kidney IgG  deposition (bottom, scale bar: 50 μm) were visualized using immunofluorescence  (n = 3, biological replicates). Data are presented as Immunofluorescent  images (K) and quantification bar graphs (L). Data information: All data are representative of at least 3 individual experiments. Statistics, two-tailed Student's t test; ns: not significant, *p < 0.5, **p < 0.01, ***p < 0.001. Error bars represent SD.",
    "ncbi_link": "Goliath: 59044"
  },
  {
    "caption": "(L) Endogenous K48-linked ubiquitination  of HA-Goliath  in GOLIATH-overexpressed Jurkat T cell with or without Cpt1a  knockdown.",
    "ncbi_link": "Cpt1a: 1374
GOLIATH: 55819"
  },
  {
    "caption": "(M) Endogenous ubiquitination  of HA-Goliath  with indicated treatment in GOLIATH-knockdown  Jurkat T cell  reconstituted with HA-tagged GOLIATH  (WT) or Ring-truncated GOLIATH  (ΔR).",
    "ncbi_link": "HA: 
GOLIATH: 55819"
  },
  {
    "caption": "A - F' Upper panels (A - F) show morphology of c4da neurons of the indicated genotypes at the third instar larval stage, lower panels (A' - F') show c4da neuron morphology at 18 h after puparium formation (APF). Neurons were labeled by CD8::GFP expression under ppk-GAL4 or by tdtomato expression in MARCM clones. (A, A') C4da neurons expressing control Orco dsRNA. Scale bars are 100 μm in A (for larval images) and 50 μm in A' (for pupal images). (B, B') C4da neurons expressing PP2A-29B dsRNA. (C, C') Homozygous PP2A-29BGE16781 mutant c4da neuron MARCM clones. (D, D') Homozygous PP2A-29BGE16781 mutant c4da neuron MARCM clones expressing UAS-HAPP2A-29B. (E, E') C4da neurons expressing dominant-negative Mts. (F, F') Homozygous mtss5286 mutant c4da neuron MARCM clones. G Penetrance of pruning defects at 18 h APF in A' - E'. ** P<0.005, *** P<0.0005, Fisher's exact test. Number of neurons for each genotype are given in the figure, the number of animals is given below in parentheses. H Severity of pruning defects at 18 h APF in A' - E' as assessed by number of primary and secondary dendrites attached to soma at 18 h APF. Data are mean +/- s. d., ** P<0.005, *** P<0.0005, Wilcoxon's test. Numbers of neurons (animals) for each genotype are given in the figure. ",
    "ncbi_link": "HA: 
tdtomato: 
GAL4: 855828
Mts: 45959
mts: 45959
Orco: 40650
PP2A-29B: 2768940
ppk: 34843"
  },
  {
    "caption": "A-J The indicated Sox14 or Mical constructs were tested for their ability to suppress pruning defects induced by PP2A-29B dsRNA expression. C4da neurons were labeled by CD8::GFP expression under ppk-GAL4, and dendrite pruning defects were assessed at 18 h APF. Panels A - E show effects of Sox14/Mical pathway manipulations alone, panels F - J show neurons coexpressing PP2A-29B dsRNA. The scale bar in A is 50 μm. (A, F) C4da neurons (co-)expressing lacZ. (B, G) C4da neurons (co-)overexpressing Sox14. (C, H) C4da neurons (co-)overexpressing Mical. (D, I) C4da neurons (co-)expressing Mical∆redox. (E, J) C4da neurons (co-)expressing Mical∆CH. K Penetrance of pruning defects in panels A - J. * P<0.05, *** P<0.0005, Fisher's exact test. Numbers of neurons (animals) for each genotype are given in the figure the numbers of animals are given below in parentheses. L Severity of pruning defects in panels A - J as assessed by number of primary and secondary dendrites attached to soma at 18 h APF. Data are mean +/- s. d., * P<0.05, *** P<0.0005, Wilcoxon's test. Numbers of neurons (animals) for each genotype are given in the figure. ",
    "ncbi_link": "GAL4: 855828
lacZ: 945006
Mical: 41225
PP2A-29B: 2768940
ppk: 34843
Sox14: 37822"
  },
  {
    "caption": "C4da neurons were labeled by CD8::GFP expression under ppk-GAL4, and expression of Sox14 was assessed by immunofluorescence. A - C Sox14 stainings at 2 h APF. (A) Control c4da neurons. (B) C4da neurons expressing PP2A-29B dsRNA. (C) C4da neuron expressing dominant-negative Mts. D Quantification of Sox14 expression in (A - C). C4da neuron Sox14 expression was normalized to Sox14 expression in neighboring ddaE c1da neurons (identified by characteristic cell body shape). Data are mean +/- s. d.. The numbers of neurons (animals) for each genotype are given in each graph (data were not derived from independent experiments). n. s., not significant, *** P<0.0005, Wilcoxon's test. ",
    "ncbi_link": "GAL4: 855828
Mts: 45959
PP2A-29B: 2768940
ppk: 34843"
  },
  {
    "caption": "C4da neurons were labeled by CD8::GFP expression under ppk-GAL4, and expression of Mical was assessed by immunofluorescence. E - H Mical stainings at the indicated time points. (E) Mical expression in control c4da neurons at 2 h APF. (F) Mical expression in c4da neurons expressing dominant-negative Mts at 2 h APF. (G) Mical expression in c4da neurons expressing PP2A-29B dsRNA at 2 h APF. (H) Mical expression in c4da neurons expressing Orco dsRNA at 0 h APF. (I) Mical expression in c4da neurons expressing PP2A-29B dsRNA at 0 h APF. J Quantification of Mical expression in (E - I). C4da neuron Mical expression was normalized to Mical expression in neighboring ddaE c1da neurons (marked by asterisks). Data are mean +/- s. d.. The numbers of neurons (animals) for each genotype are given in each graph (data were not derived from independent experiments). n. s., not significant, ** P<0.005, *** P<0.0005, Wilcoxon's test. Data information: Scale bars in A and E are 10 μm. ",
    "ncbi_link": "GAL4: 855828
Mts: 45959
Orco: 40650
PP2A-29B: 2768940
ppk: 34843"
  },
  {
    "caption": " A - G The indicated UAS-tsr constructs were tested for their ability to suppress pruning defects induced by PP2A-29B dsRNA expression. Suppression tests were performed as in Figure 2. Panels A - C show effects of the expression of wild type or phosphomutant tsr variants on dendrite pruning, panels D - G show neurons coexpressing PP2A-29B dsRNA. (A, E) C4da neuron (co-)overexpressing wild type tsr. (B, F) C4da neuron (co-)overexpressing tsr S3A. (C, G) C4da neuron (co-)overexpressing tsr S3E. The arrow in panel G denotes a characteristic varicosity at the tip of an unpruned dendrite. (D) C4da neuron co-expressing PP2A-29B dsRNA and lacZ as a UAS titration control. H Penetrance of pruning defects in panels A - G. * P<0.05, Fisher's exact test. Numbers of neurons (animals) for each genotype are given in the figure. I Severity of pruning defects in panels A - G as assessed by number of primary and secondary dendrites attached to soma at 18 h APF. Data are mean +/- s. d., * P<0.05, Wilcoxon's test. Numbers of neurons (animals) for each genotype are given in the figure. ",
    "ncbi_link": "lacZ: 945006
PP2A-29B: 2768940
tsr: 37841"
  },
  {
    "caption": "J - L GFP-tagged Drosophila cofilin (GFP::tsr) was expressed in c4da neurons under ppk-GAL4, and its localization was assessed at the indicated developmental stages by live imaging. Panels J - L show GFP::tsr localization in c4da neurons at the third instar stage, panels J' - L' show GFP::tsr localization in c4da neurons at 6 h APF. (J, J') Control c4da neurons expressing Orco dsRNA. (K, K') C4da neurons expressing Mical dsRNA. (L, L') C4da neurons expressing PP2A-29B dsRNA. M Quantification of GFP::tsr punctae in samples J - L'. Data are mean +/- s. d., the numbers of neurons (animals) analyzed for each genotype are given in the figure (data were not derived from independent experiments). ** P<0.005, *** P<0.0005, n. s., not significant, Wilcoxon's test. ",
    "ncbi_link": "GAL4: 855828
Mical: 41225
Orco: 40650
PP2A-29B: 2768940
ppk: 34843"
  },
  {
    "caption": "A - H Genetic interactions between PP2A-29B and actin regulators during dendrite pruning. The indicated manipulations of actin regulators were tested for their ability to suppress pruning defects induced by PP2A-29B dsRNA expression. Suppression tests were performed as in Figure 2. (A) C4da neuron coexpressing PP2A-29B dsRNA and tdtomato as suppression control. (B) C4da neuron coexpressing PP2A-29B dsRNA and GFP::tsr. (C) C4da neuron coexpressing PP2A-29B dsRNA and RacN17. (D) C4da neuron coexpressing PP2A-29B dsRNA and RhoN19. (E) C4da neuron expressing PP2A-29B dsRNA in ena210/+ background. (F) C4da neuron coexpressing PP2A-29B dsRNA and Orco dsRNA as suppression control. (G) C4da neuron coexpressing PP2A-29B dsRNA and Chicadee dsRNA. (H) C4da neuron coexpressing PP2A-29B dsRNA and moesin dsRNA. I Penetrance of pruning defects in panels E - L. n. s., not significant, Fisher's exact test. Numbers of neurons (animals) for each genotype are given in the figure. J Severity of pruning defects in panels E - L as assessed by number of primary and secondary dendrites attached to soma at 18 h APF. Data are mean +/- s. d., * P<0.05, ** P<0.005, *** P<0.0005, Wilcoxon's test. Numbers of neurons (animals) for each genotype are given in the figure. ",
    "ncbi_link": "tdtomato: 
Chicadee: 33834
ena: 37201
moesin: 31816
Orco: 40650
PP2A-29B: 2768940
Rac: 38146
Rho: 38168
tsr: 37841"
  },
  {
    "caption": "Representative confocal microscope images of L6 cells stained with IP-1 (Iron Probe 1) or transfected with IRE-CFP (Iron Regulatory Element) reporter after iron treatment (FeSO4, 250 µM) for 24 h.",
    "ncbi_link": "CFP: 
IRE: 
Iron Regulatory Element: "
  },
  {
    "caption": "Relative gene expressions - ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin (SLC40A1, transferrin receptor 1 (tfr1, TFRC) - normalized to 18sr RNA expression after iron treatment (FeSO4, 250 µM) for 24 h. *P < 0.05 (unpaired Student's t-test versus Basal).",
    "ncbi_link": "18sr RNA: 
ferritin heavy chain: 25319
FTH: 25319
ferritin light chain: 29292
FTL: 29292
ferroportin: 170840
SLC40A1: 170840
tfr1: 64678
TFRC: 64678
transferrin receptor 1: 64678"
  },
  {
    "caption": "Representative epi-immunofluorescent images of L6 cells transfected with myc-RHEB Q46L and immuno-stained against LC3B and myc after iron treatment (FeSO4, 250 µM) for 24 h.",
    "ncbi_link": "myc: 
RHEB: "
  },
  {
    "caption": "Ferrozine-based colorimetric measurement of intracellular iron in wild-type (wt) L6 and RHEB-Q64L L6 cells after iron treatment (50 µM or 250 µM) for 24 h.",
    "ncbi_link": "RHEB: "
  },
  {
    "caption": "Representative confocal images of wt L6 and RHEB-Q64L L6 cells pulsed with Lysotracker Deep Red and immuno-stained against LC3B after iron treatment (250 µM, 24 h).",
    "ncbi_link": "RHEB: "
  },
  {
    "caption": "Quantification of LC3B-free lysosome numbers in (E). Experiments were repeated three times, and one representative experiment is presented here. *P < 0.05 (multiple unpaired Student's t-test versus Basal in wt and RHEB Q64L cells)",
    "ncbi_link": "RHEB: "
  },
  {
    "caption": "Representative TEM images of wt L6 and RHEB-Q64L cells after iron treatment (250 µM, 24 h).",
    "ncbi_link": "RHEB: "
  },
  {
    "caption": "Representative western blot images and quantifications of phospho-IRS1 (Y612, indicated by arrowhead) and AKT (T308, indicated by arrowhead) to GAPDH in wt and RHEB-Q64L L6 cells stimulated with insulin (100 nM, 5 min) after iron treatment (250 µM, 24 h). *P < 0.05 (multiple unpaired Student's t-test versus Basal in wt and RHEB Q64L cells)",
    "ncbi_link": "RHEB: "
  },
  {
    "caption": "Representative western blot images of phospho-UVRAG S550 and total UVRAG in L6 cells transfected with FLAG-UVRAG and FLAG pulldown after iron treatment (250 µM, 4 h and 24 h) followed by withdrawal for 1 h and 3 h.",
    "ncbi_link": "FLAG: 
UVRAG: "
  },
  {
    "caption": "Live cell imaging analysis of L6 cells transfected with LAMP1-RFP from Movie EV2: lysosomal number in L6 cells after iron treatment (250 µM, 24 h) followed by withdrawal for 4 h with or without Torin1 (200 nM).",
    "ncbi_link": "LAMP1: 
RFP: "
  },
  {
    "caption": "Live cell imaging analysis of L6 cells transfected with LAMP1-RFP from Movie EV2: speed (F) in L6 cells after iron treatment (250 µM, 24 h) followed by withdrawal for 4 h with or without Torin1 (200 nM).",
    "ncbi_link": "LAMP1: 
RFP: "
  },
  {
    "caption": "Relative fold repression for let-7a reporter in RAW 264.7 cells during LPS treatment (mean+/- s.e.m., n=3) (B). The schematic representation of the constructs used for luciferase assays are shown.",
    "ncbi_link": "let-7a: 723965"
  },
  {
    "caption": "Relative levels of pro-inflammatory cytokines TNF-ɑ and IL-6 mRNA, a target of let-7a miRNA, have been plotted against time of LPS stimulation, 18S rRNA was used for normalization (mean+/- s.e.m., n=2 (IL-6), n=3 (TNF-α)) (C).",
    "ncbi_link": "18S rRNA: 
IL-6: 16193
let-7a: 723965
TNF-ɑ: 21926
TNF-α: 21926"
  },
  {
    "caption": "Time dependent Ago2 phosphorylation and its miRNA binding in LPS treated macrophage cells. RAW 264.7 cells were transfected with FH-Ago2 expression plasmid and treated with LPS (1ng/ml) for different time points. Ago2 was pulled down using anti-FLAG beads and the levels of Ago-associated let-7a miRNA were measured by qRT-PCR. Quantity of immunoprecipitated Ago2 was detected in western blot analysis with anti-HA antibody and used for normalization of amounts of miRNA detected by qRT-PCR. Levels of cellular let-7a were measured by Northern blot and U6 RNA was used as loading control. Relative levels of cellular and Ago2 bound let-7a were plotted (mean+/- s.e.m., n=3) (D).",
    "ncbi_link": "U6: 
Ago2: 27161
let-7a: 723965"
  },
  {
    "caption": "Time dependent Ago2 phosphorylation and its miRNA binding in LPS treated macrophage cells. RAW 264.7 cells were transfected with FH-Ago2 expression plasmid and treated with LPS (1ng/ml) for different time points. Phosphorylated Ago2 (pY-Ago2) level was measured using 4G10 antibody specific for phosphorylated tyrosine. Phosphorylated Ago2 (pY-Ago2) band intensities were normalized against total Ago2 detected with HA specific antibody that was also used for Ago2 pull down (E, upper panel). Relative 4G10 intensities were plotted from three independent experiments (mean+/- s.e.m) (E, lower panel).",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "Time dependent Ago2 phosphorylation and its miRNA binding in LPS treated macrophage cells. RAW 264.7 cells were transfected with FH-Ago2 expression plasmid and treated with LPS (1ng/ml) for different time points. Primary cells (PEC) were isolated from BALB/c mice and endogenous Ago2 was immunoprecipitated with anti-Ago2 (eIF2C2) antibody and phospho tyrosine level of Ago2 was measured using 4G10 antibody. Relative intensities of phospho-Ago2 against total amount of immunoprecipitated Ago2 were quantified and mentioned below the lanes (mean+/- s.e.m., n=3) (F, upper panel). Similar experiments were done with FH-Ago1 and Ago3 and levels of Phosphotyrosine in immunoprecipitated FH-Ago1 and FH-Ago3 were measured in RAW 264.7 cells (F, lower panel).",
    "ncbi_link": "Ago1: 26523
Ago2: 27161
Ago3: 192669"
  },
  {
    "caption": "Effect of knockdown of different phosphatases on miRNA-mediated repression in 24hrs LPS treated RAW 264.7 cells. Knockdown of PP2A, MKP1, MKP3 or SHP1/2 was checked by western blot analysis done with lysates of cells treated with respective siRNAs. β-Actin was used as loading control (G).",
    "ncbi_link": "MKP1: 19252
MKP3: 67603
PP2A: 19052
SHP1: 15170"
  },
  {
    "caption": "Effect of knockdown of different phosphatases on miRNA-mediated repression in 24hrs LPS treated RAW 264.7 cells. Luciferase based let-7a miRNA reporter assay was done in LPS-treated cells downregulated for specific phosphatases. Levels at 0 hrs time point were taken as units (mean +/- s.e.m., n=4) (H).",
    "ncbi_link": "Luciferase: 
let-7a: 723965"
  },
  {
    "caption": "Effect of knockdown of different phosphatases on miRNA-association of Ago2 in 24hrs LPS treated RAW 264.7 cells. Ago2 associated let-7a was estimated by qRT-PCR in LPS treated cells depleted for specific phosphatases. let-7a miRNA level was normalized against respective FH-Ago2 bands (mean+/- s.e.m., n=3) (I).",
    "ncbi_link": "let-7a: 723965"
  },
  {
    "caption": "Effect of PP2A knock-down on Ago2 phosphorylation and its miRNA association. Phospho Ago2 levels were measured in siCon and siPP2A transfected cells upon 24hrs of LPS treatment using Phospho Tyrosine specific 4G10 antibody. HA-Ago2 was detected with anti-HA antibody (J). Immunoprecipitated Ago2 content was used for normalization for both miRNA and mRNA levels in above mentioned experiments.",
    "ncbi_link": "PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knock-down on Ago2 phosphorylation and its miRNA association. Cellular miRNA levels (K, left panel mean +/- s.e.m., n=3) and Ago2 associated miRNAs content in cells treated with siCon or siPP2A were measured using qRT-PCR and plotted (K, right panel, mean+/- s.e.m., n=3).",
    "ncbi_link": "PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knock-down on Ago2 phosphorylation and its miRNA association. Ago2 associated IL-1β mRNA level was estimated in siCon and siPP2A treated cells which were stimulated with LPS for 24hrs (mean+/- s.e.m., n=3) (L).",
    "ncbi_link": "IL-1β: 16176
PP2A: 19052"
  },
  {
    "caption": "Effect of Okadaic acid (OA; 100nM), the PP2A inhibitor, on miRNA activity. Change in fold repression for a let-7a reporter upon LPS exposure in control and OA treated cells (mean+/- s.e.m., n=3) (C).",
    "ncbi_link": "let-7a: 723965"
  },
  {
    "caption": "Schematic representation of the in vitro phosphatase assay (upper panel). PP2A was immunoprecipitated from 24hrs LPS treated RAW 264.7 cells and were incubated in vitro with wild type or phosphorylation defective FH-Ago2 mutant (Ago2Y529F) isolated from HEK293 cells transfected with respective expression constructs. Phosphorylated Ago2 (pYAgo2) levels were measured by western blot analysis using anti-phospho Tyrosine specific 4G10 antibody. Relative intensities were quantified by densitometric analysis and mentioned below the respective panels. FH-Ago2 was detected by anti-HA antibody (Lower panel).",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "Defective de novo miRNP formation in cells pre-treated with PP2A inhibitor. Ago2 associated (F) and total (G) miR-122 levels were measured by qRT-PCR and normalized against immuneprecipitated FH-Ago2 content and U6 RNA respectively. Values obtained upon 14 hrs of DOX treatment were considered as unit and relative values obtained upon 24 hrs of DOX treatment are plotted. All samples were treated for 24 hrs with LPS (mean+/- s.e.m., n=4).",
    "ncbi_link": "U6: 
miR-122: 387231"
  },
  {
    "caption": "PTPA is an essential factor for PP2A mediated dephosphorylation of Ago2. Effect of PTPA depletion on Ago2 phosphorylation level in RAW 264.7 cells (I). Phosphorylated Ago2 level was measured by western blot in HA-immunoprecipitated materials isolated from either siCon or siPTPA transfected cells expressing FH-Ago2 upon 24 hrs of LPS treatment using a phosphotyrosine specific 4G10 antibody (I, left panel). The PTPA was detected with anti PTPA antibody, β-Actin was used as loading control (I, right panel).",
    "ncbi_link": "PTPA: 110854"
  },
  {
    "caption": "Effect of PTPA depletion on Ago2 associated miRNAs and mRNAs. Ago2-associated miRNA (J, left panel) (mean+/- s.e.m., n=3) and mRNA levels (J, right panel) (mean+/- s.e.m., n=2) were also quantified using qRT-PCR.",
    "ncbi_link": "PTPA: 110854"
  },
  {
    "caption": "PP2A was immunoprecipitated from siCon or siPTPA treated RAW 264.7 cells treated with LPS for 24 hrs and was incubated in vitro with FH-Ago2 isolated from FH-Ago2 stable HEK293 cells and upon the assay reaction, the phospho-Ago2 level was measured by western blot analysis using phosphotyrosine specific 4G10 antibody (K, right panel).",
    "ncbi_link": "PTPA: 110854"
  },
  {
    "caption": "Cytokine mRNA levels like IL-10, TNF-α and IL-6 were quantified after 24 hrs of Ld infection in RAW 264.7 (C, upper panel mean +/- s.e.m., n=3) and mouse peritoneal macrophage PEC (mean+/- s.e.m., n=3) (C, Lower panel).",
    "ncbi_link": "IL-10: 16153
IL-6: 16193
TNF-α: 21926"
  },
  {
    "caption": "Effect of Ld infection on Ago2 phosphorylation and its miRNA association. RAW 264.7 cells were transfected with FH-Ago2 expression construct and infection was done for various time points followed by FH-Ago2 pull down using anti-FLAG beads. Phosphorylated Ago2 levels were checked during the course of Ld infection (D).",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "Phosphorylation levels of Ago2 were measured by doing endogenous Ago2 pull down using Ago2 specific antibody after 4 hrs of infection and quantified along with Ago2 associated let-7a level measurement in primary macrophages (mean+/- s.e.m., n=2) (E, left panel) and in RAW 264.7 cells (mean+/- s.e.m., n=3) (E, right panel) .",
    "ncbi_link": "let-7a: 723965"
  },
  {
    "caption": "Schematic representation of in vitro phosphatase assay (F, upper panel). PP2A, MKP1, MKP3, or SHP1 were immunoprecipitated individually from naïve or Leishmania infected macrophage cells and were incubated in vitro with FH-Ago2 isolated from FH-Ago2 stable HEK293 cells. Phosphorylated Ago2 level was detected by western blot analysis using phosphotyrosine specific 4G10 antibody (F, lower panel) and measured by densitometry. BC; Bead Control.",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "PP2A MKP3, or SHP1 were immunoprecipitated individually from naïve or Leishmania infected macrophage cells and were incubated in vitro with FH-Ago2 isolated from FH-Ago2 stable HEK293 cells. Relative intensity of 4G10 specific band against immunoprecipitated Ago2 was plotted (mean+/- s.e.m., n=3) (G). BC; Bead Control.",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "Effect of PP2A knockdown on Ago2 phosphorylation and miRNA-Ago2 binding in RAW 264.7 cells infected with Ld. Cells were co-transfected with siRNA and FH-Ago2 expression plasmid. Phosphorylated Ago2 levels were detected after 4 hrs of infection in siCon or siPP2A transfected cells (H).",
    "ncbi_link": "Ago2: 27161
PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knockdown on Ago2 phosphorylation and miRNA-Ago2 binding in RAW 264.7 cells infected with Ld. Cells were co-transfected with siRNA and FH-Ago2 expression plasmid. Ago2 associated let-7a levels were also estimated and plotted (mean+/- s.e.m., n=4) (I).",
    "ncbi_link": "Ago2: 27161
let-7a: 723965
PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A downregulation or inhibition on pro and anti-inflammatory cytokine levels in Ld infected macrophage. IL-10 levels were measured after Ld infection in PP2A knocked-down RAW 264.7 cells (mean+/- s.e.m., n=3) and in PEC (mean+/- s.e.m., n=3). IL-6 was also measured in RAW cells after OA treatment (mean+/- s.e.m., n=5) and also in PEC pre-treated with OA (mean+/- s.e.m., n=3). Values obtained at 0 hrs (non-infected) or non-OA treated samples were considered as unit in each case. IL-6 protein level (n=5) in cell supernatant was also measured by ELISA after Ld infection in PP2A knock-down RAW 264.7 cells.",
    "ncbi_link": "IL-10: 16153
IL-6: 16193
PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knock-down on parasite internalization Internalized parasites were imaged in RAW 264.7 cells stained with Phalloidin-Alexa 488 (green) for actin cytoskeleton detection and Ld was detected by indirect immunofluorescence done for parasite specific membrane protein GP63 (red) (B).",
    "ncbi_link": "PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knock-down on parasite internalization and cellular IL-1β level. Number of Ld internalized was measured in control and PP2A knock-down cells and relative numbers of parasites within infected cells were plotted (C, left panel, (mean+/- s.e.m., n=20 cells). IL-1β mRNA levels were also quantified in those cells by qRT-PCR done for total cellular RNA [C, right panel, (mean+/- s.e.m., n=3)]. Scale bar 20 µm. 4x Zoomed insets are shown.",
    "ncbi_link": "IL-1β: 16176
PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A knockdown on IL-10 level in Ld-infected cells expressing phosphorylation defective mutant of Ago2. In RAW 264.7 cells, depleted for endogeneous Ago2 (using a specific siRNA against the 3'UTR of Ago2 mRNA), either the wild type or Y529F mutant of FH-Ago2 (without having the 3'UTR of Ago2) was expressed in siCon or siPP2A treated RAW 264.7 cells. IL-10 mRNA level was measured subsequent to Ld infection. Relative IL-10 levels were plotted. Expression levels in non-infected siCon treated cells in each case were designated as unit (mean+/- s.e.m., n=3).",
    "ncbi_link": "Ago2: 239528
IL-10: 16153
PP2A: 19052"
  },
  {
    "caption": "Effect of PP2A inhibitor OA on Ld internalization and cytokine production in RAW 264.7 cells. In RAW 264.7 cells transfected with FH-Ago2 WT and Y529F mutant and pre-treated with OA, Leishmania internalization was measured microscopically. In images obtained, Ago2 was detected with α-HA (detected at 405nm) and Leishmania was stained for GP63 (detected at 564nm) (E).",
    "ncbi_link": "Ago2: 27161"
  },
  {
    "caption": "Effect of PP2A inhibitor OA on Ld internalization and cytokine production in RAW 264.7 cells. In RAW 264.7 cells transfected with FH-Ago2 WT and Y529F mutant and pre-treated with OA, Leishmania internalization was measured microscopically. Quantitative measurement of GP63 positive structures was done and quantitative data per 100 infected cells was plotted. Scale bar 10 µm. RNA was isolated from different experimental sets and TNF-α, IL-1β and IL-10 mRNA levels were estimated (mean +/- s.e.m., n=3) (F).",
    "ncbi_link": "Ago2: 27161
IL-10: 16153
IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "Effect of GW4869, the inhibitor of exosome mediated miRNA export, on exosomal miRNA content released by LPS stimulated cells. The level of miRNAs, let-7a and miR-155 were measured in exosomes (EV) released from LPS activated cell after GW4869 treatment. Values for EVs from naïve macrophages treated without LPS without GW4869 treatment was set as unit. Values are mean+/- s.e.m. and, n=3",
    "ncbi_link": "miR-155: 387173
let-7a: 723965"
  },
  {
    "caption": "Effect of GW4869 on cellular cytokine levels in LPS treated cells. The effect of GW4869 on cellular expression of pro-inflammatory cytokines IL-1β and TNF-α in LPS-activated macrophages were measured and normalized against 18S rRNA. Values in naive RAW 264.7 cells without GW4869 and LPS treatment were set as unit. Values are mean+/- s.e.m. and, n=3",
    "ncbi_link": "18S rRNA: 
IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "Effect of siRNA-mediated downregulation of protein HuR on cellular expression of pro-inflammatory cytokines. In the left panel of F, effect of siRNA treatment on cellular cytokine mRNA levels in LPS-stimulated RAW 264.7 cells is shown. Relative levels measured against 18S rRNA are plotted. The effect of HuR depletion on cellular miR-155 content has been measured and relative values normalized against U6 snRNA are plotted (right panel, F).",
    "ncbi_link": "18S rRNA: 
U6 snRNA: 
HuR: 15568
miR-155: 387173"
  },
  {
    "caption": "The amount of let-7a bound to Ago2 after LPS stimulation in presence and absence of siHuR has been calculated and relative values has been normalized to immunoprecipitated Ago2 (G) .Values are mean+/- s.e.m. and, n=3",
    "ncbi_link": "HuR: 15568
let-7a: 723965"
  },
  {
    "caption": "Effect of HuR expression on inflammatory responses in macrophage cells. Effect of ectopic expression of HuR on exosomal let-7a content in naive macrophage cells (H, right panel). HuR over expression was checked by western blot (H, left panel). Transfection was done either with pCIneo (control plasmid) of HA-HuR expression construct and their effect on cellular pro-inflammatory cytokine mRNA levels in RAW64.7 cells was determined. Values in control set were taken as unit. Values are mean+/- s.e.m. and, n=3",
    "ncbi_link": "HA: 
HuR: 1994
let-7a: 723965"
  },
  {
    "caption": "Effect of HuR expression on inflammatory responses in macrophage cells. The effect of HuR expression on production of pro-inflammatory cytokine TNF-α in RAW 264.7 cells was measured. mRNA and protein level of TNF-α was quantified. Values obtained with pCINeo expression and without LPS treatment was taken as unit (I). Transfection was done either with pCIneo (control plasmid) of HA-HuR expression construct and their effect on cellular pro-inflammatory cytokine mRNA levels in RAW64.7 cells was determined. Values in control set were taken as unit. Values are mean+/- s.e.m. and, n=3",
    "ncbi_link": "HA: 
HuR: 1994
TNF-α: 21926"
  },
  {
    "caption": "Effect of HA-HuR expression on p38 mediated activation of downstream signalling events. The Levels of p-p38 and p-MSK1 have been monitored by western blotting done with cell extracts prepared from HA-HuR and control plasmid transfected, untreated and LPS treated RAW 264.7 cells. β-Actin blot was used as loading control.",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Downregulation of HuR in Ld-infected macrophages. Effect of proteasomal inhibitor MG132 treatment on HuR protein levels in control and 6 hrs of Ld-infected RAW 264.7 cells. In parallel assays levels of pro-inflammatory cytokine TNF-α was measured in Ld-infected cells either with no treatment or pre-treated with MG132 (L). Values are mean+/- s.e.m. and, n=3.",
    "ncbi_link": "TNF-α: 21926"
  },
  {
    "caption": "effect of HA-HuR expression on PP2A protein levels",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "effect of HA-HuR expression on PP2A RNA levels were scored.",
    "ncbi_link": "HA: 
HuR: 1994
PP2A: 19052"
  },
  {
    "caption": "Expression profiles of HuR, PP2A and miRNA let-7a are connected to IL-6 expression in RAW 264.7 cells. Data obtained from experiments described in previous figures are summed up to plot the changes in IL-6 mRNA levels against time of LPS treatment along with changes in PP2A, miRNA let-7a and HuR (D).",
    "ncbi_link": "IL-6: 16193
let-7a: 723965"
  },
  {
    "caption": "Change in expression of IL-6 is connected to changes in let-7a concentration. The mathematical equation fitting the curve are shown here. Y represents concentration of IL-6 and X represents miRNA let-7a concentration. A1 is the initial IL-6 levels and A2 is the changed level. LogX0 is the mid-point of value 0.34, a concentration of let-7a where Il-6 expression is reduced to half",
    "ncbi_link": "IL-6: 16193
Il-6: 16193
let-7a: 723965"
  },
  {
    "caption": "variations of IL-6 expression with the altered level of PP2A (black) and HuR (red). For both cases, the data were fitted to an equation, which is shown above. The parameter m denotes the expression level of PP2A/HuR which corresponds to the maximum IL-6 expression; w denotes the width of the distributions for both cases. For PP2A and HuR, the values of m were found to be 0.6 and 0.9 respectively and A is a constant (F).",
    "ncbi_link": "IL-6: 16193"
  },
  {
    "caption": "Effect of HA-HuR expression on Ld infection of RAW 264.7 cells. Effect of HuR expression on internalized parasite number and cytokine expression in RAW 264.7 cells. HA-HuR was transfected to RAW 264.7 cells and infection was given for 24 hrs at a host to parasite 1:10 ratio. Ld was stained with CFSE dye and parasite internalization was detected by counting the CFSE positive structures inside the cells. HA-HuR was immunostained with anti-HA antibody and detected by secondary antibody tagged with AlexaR564 (A).",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of HA-HuR expression on Ld infection of RAW 264.7 cells. Effect of HuR expression on internalized parasite number HA-HuR was transfected to RAW 264.7 cells and infection was given for 24 hrs at a host to parasite 1:10 ratio. Ld was stained with CFSE dye and parasite internalization was detected by counting the CFSE positive structures inside the cells. In the zoomed part of the merged picture are used to show the internalized parasite. Internalized parasites present in HA-HuR positive cells were counted and compared against untransfected cells without HA-HuR expression (B).",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of HA-HuR expression on Ld infection of RAW 264.7 cells. Effect of HuR expression on cytokine expression in RAW 264.7 cells. HA-HuR was transfected to RAW 264.7 cells and infection was given for 24 hrs at a host to parasite 1:10 ratio. Levels of expression of different cytokines are measured in control or HA-HuR expressing RAW 264.7 cells infected with Ld (C). Scale bar 20 µm. Values are mean+/- s.e.m. and, n=3.",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of expression of HA-HuR on Ld infection in mice liver. Scheme for animal experiment done with HA-HuR expression in liver is shown. Also the HA-HuR level was detected in the liver tissue by western blot analysis using anti-HA antibody (F).",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of expression of HA-HuR on Ld infection in mice liver. Parasite load in liver tissues were estimated by measuring Ld DNA in infected tissue using specific primer for Ld minicircle kDNA. Values are mean+/- s.e.m. and, n=5 (G).",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of expression of HA-HuR on Ld infection in mice liver. TNF-α (Values are mean+/- s.e.m. and, n=5) and IL-10 (Values are mean+/- s.e.m. and, n=4) mRNA levels were checked from RNA isolated from liver tissues and 18S rRNA normalized Ct values were plotted (H and I, left panels). Relative fold change was calculated by ΔΔCt method and the values plotted for Ld count, TNF-α and IL-10 mRNA levels (G mean +/- s.e.m., (n=5), H mean +/- s.e.m., (n=6) and I mean +/- s.e.m., (n=4), right panel).",
    "ncbi_link": "18S rRNA: 
HA: 
HuR: 1994
IL-10: 16153
TNF-α: 21926"
  },
  {
    "caption": "Effect of HA-HuR plasmid tail-vein injection on mice spleen. Levels of HA-HuR were undetectable in mice spleen after expression plasmid was injected. Sample from one liver tissue of HA-HuR injected group was used as a positive control of HA-HuR expression in moue liver after tail vein injection of HuR encoding plasmid (J).",
    "ncbi_link": "HA: 
HuR: 1994"
  },
  {
    "caption": "Effect of HA-HuR plasmid tail-vein injection on mice spleen. Simultaneously, TNF-α mRNA levels were checked in spleen total RNA (K).",
    "ncbi_link": "HA: 
HuR: 1994
TNF-α: 21926"
  },
  {
    "caption": "Effect of antimonial drug resistant and sensitive forms of the Ld (LdR and LdS) on cellular cytokine level RAW 264.7 cells were infected with Antimony sensitive (LdS-Ag83) and antimony resistant (LdR-BHU569) form of Ld for 24 hours along with uninfected cells kept as control. IL-10 (A) and TNF-α (B) were measured at mRNA level by qRT-PCR after infection (mean+/- s.e.m. and, n=4).",
    "ncbi_link": "IL-10: 16153
TNF-α: 21926"
  },
  {
    "caption": "Effect of ectopic expression of HuR and PP2A inhibitor OA treatment on LdR infection of macrophage cell. RAW 264.7 cells were transfected with HA-HuR or pCIneo followed by 2 hrs of pretreatment with OA. These cells were then infected with LdR for 24 hrs. Pro-inflammatory cytokines TNF-α (right panel; mean+/- s.e.m., n=3) and IL-1β (left panel; mean+/- s.e.m. and, n=4) were measured at mRNA level and relative values are plotted. Values without OA treatment was set as control.",
    "ncbi_link": "HA: 
HuR: 1994
IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "Effect of HuR over expression on LdR infection in mice liver. Pro-inflammatory cytokines TNF-α (left panel) and IL-1β (right panel) level were measured at mRNA level in liver (H).",
    "ncbi_link": "HuR: 1994
IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "Effect of HuR over expression on LdR infection in mice liver. Parasite load was measured in infected liver tissue by using specific primer against kinetoplastid minicircle DNA of Ld (I). Values are mean+/- s.e.m. and, n=6).",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "A Lysates of HeLa cells stably expressing GFP alone or GFP-FXR1 were subjected to immunoprecipitation using GFP-Trap beads (GFP-IP), analysed by Western blot and quantified (shown a mean value, *P < 0.05, **P < 0.01; N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "B Lysates of HeLa cells stably expressing GFP alone or 3xGFP-Nup85 were immunoprecipitated using GFP-Trap beads (GFP-IP), analysed by Western blot and quantified (SE, short exposure, LE, long exposure) (shown a mean value, *P < 0.05; N = 3).",
    "ncbi_link": "GFP: 
Nup85: 79902"
  },
  {
    "caption": "E HeLa cells stably expressing GFP-FXR1 were analysed by immunofluorescence microscopy for GFP and mAb414, which labels FG-Nups. The magnified framed regions are shown in the corresponding numbered panels. The arrowheads indicate NE and cytoplasmic localization of GFP-FXR1.",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "F HeLa cells stably expressing GFP-Nup107 were synchronized by double thymidine block and released for 12 hours, permeabilized with Triton/SDS or digitonin for antibodies to access the nuclear and cytoplasmic or cytoplamsic side of the nucleus, respectively, and analysed by immunofluorescence microscopy.",
    "ncbi_link": "GFP: 
Nup107: 57122"
  },
  {
    "caption": "B HeLa cells stably expressing GFP, GFP-FXR1 wild type (WT) and GFP-FXR1 mutated in the sequence recognized by FXR1 siRNA-1 (GFP-FXR1-MUT-siRNA1) were treated with the indicated siRNAs, synchronized by double thymidine block, released for 24 hours and then analysed by immunofluorescence microscopy. The percentage of cells with cytoplasmic nucleoporin granules was quantified, 1000 cells were analysed for each graph (mean ±SD, **P < 0.01; ***P < 0.001, N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "A HeLa cells were treated with the indicated siRNAs, synchronized by double thymidine block, released for 24 hours and analysed by immunofluorescence microscopy. The magnified framed regions are shown in the corresponding numbered panels. Arrowheads point to nuclear blebs observed in FXR1-deficient cells.",
    "ncbi_link": "FXR1: 8087"
  },
  {
    "caption": "B, HeLa cells stably expressing GFP, GFP-FXR1 wild type (WT) and GFP-FXR1 mutated in the sequence recognized by FXR1 siRNA-1 (GFP-FXR1-MUT-siRNA1) were treated with the indicated siRNAs, synchronized by double thymidine block, released for 24 hours and analysed by Western blot (B)",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "C HeLa cells stably expressing GFP, GFP-FXR1 wild type (WT) and GFP-FXR1 mutated in the sequence recognized by FXR1 siRNA-1 (GFP-FXR1-MUT-siRNA1) were treated with the indicated siRNAs, synchronized by double thymidine block, released for 24 hours and analysed by immunofluorescence microscopy (C). The percentage of cells with irregular nuclei was quantified, 1000 cells were analysed (mean ±SD, **P < 0.01, ***P < 0.001; N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "HeLa cells stably expressing the chromatin marker histone H2B labelled with mCherry were treated with indicated siRNAs, synchronized by double thymidine block, released for 12 hours and analysed by immunofluorescence microscopy. Time from prophase till anaphase (D), from prophase till metaphase (E), from metaphase till anaphase (F) and from anaphase till chromatin decondensation (G) was quantified.",
    "ncbi_link": "mCherry: 
H2B: 8970"
  },
  {
    "caption": "HeLa cells stably expressing the chromatin marker histone H2B labelled with mCherry were treated with indicated siRNAs, synchronized by double thymidine block, released for 12 hours and analysed by immunofluorescence microscopy. The selected frames of the movies are depicted and time is shown in minutes (H). Arrowheads point to nuclear blebs appearing during nuclear expansion of FXR1-deficient cells.",
    "ncbi_link": "mCherry: 
FXR1: 8087
H2B: 8970"
  },
  {
    "caption": "HeLa cells stably expressing the chromatin marker histone H2B labelled with mCherry were treated with indicated siRNAs, synchronized by double thymidine block, released for 12 hours and analysed by immunofluorescence microscopy. Percentage of daughter cells with irregular nuclei was quantified in (I)",
    "ncbi_link": "mCherry: 
H2B: 8970"
  },
  {
    "caption": "HeLa cells stably expressing the chromatin marker histone H2B labelled with mCherry were treated with indicated siRNAs, synchronized by double thymidine block, released for 12 hours and analysed by immunofluorescence microscopy. time from anaphase till nuclear blebs was quantified in (J).",
    "ncbi_link": "mCherry: 
H2B: 8970"
  },
  {
    "caption": "A-D HeLa cells stably expressing GFP-Nup107 were treated with indicated siRNAs, synchronized by double thymidine block, released and analysed by live video spinning disk confocal microscopy (A). The selected frames of the movies are depicted and time is shown in minutes. The onset of anaphase is indicated. The magnified framed regions with time indicated in minutes are shown in (B). White arrowheads point to the cytoplasmic GFP-NUP107 granules appearing during nuclear expansion of control and FXR1-deficient cells, yellow arrowheads point to the fussion events of GFP-NUP107 granules with NE in control cells. The percentage of cells with cytoplasmic GFP-Nup107 granules was quantified in (C). Time from anaphase till GFP-Nup107 cytoplasmic granule formation was quantified in (D). 57 cells were analysed (mean ±SD, *P < 0.05; ns = non-significant; N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087
Nup107: 57122"
  },
  {
    "caption": "A HeLa cells stably expressing GFP-Nup133 were synchronized by double thymidine block, released for 12 hours, treated or not with NaAsO2 to induce stress granule formation and with 1,6 Hexanediol, and analysed by immunofluorescence microscopy. The magnified framed regions are shown in the corresponding numbered panels.",
    "ncbi_link": "GFP: 
Nup133: 234865"
  },
  {
    "caption": "B, C HeLa cells stably expressing GFP-Nup133 were treated with the indicated siRNAs, synchronized by double thymidine block, released for 12 hours, treated with or without 1,6 Hexanediol and analysed by immunofluorescence microscopy. The magnified framed regions are shown in the corresponding numbered panels. The percentage of cells with cytoplasmic GFP-Nup133 granules was quantified in (C), 3100 cells were analysed (mean ±SD, **P < 0.01; ***P < 0.001; ****P < 0.0001; N = 3).",
    "ncbi_link": "GFP: 
Nup133: 234865"
  },
  {
    "caption": "A HeLa cells stably expressing GFP alone or GFP-FXR1 were immunoprecipitated using GFP-Trap beads (GFP-IP), analysed by Western blot and quantified (mean, *P < 0.05; N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "D Lysates of HeLa cells stably expressing GFP alone or GFP-FXR1 were subjected to immunoprecipitation using GFP-Trap beads (GFP-IP), analysed by Western blot and quantified (mean, *P < 0.05; **P < 0.01; N = 3).",
    "ncbi_link": "GFP: 
FXR1: 8087"
  },
  {
    "caption": "A, B HeLa cells stably expressing GFP-Nup133 were treated with the indicated siRNAs, synchronized by double thymidine block, released for 12 hours, treated with nocodazole to induce granule formation and washed-out as indicated and analysed by immunofluorescence microscopy. The percentage of cells with cytoplasmic GFP-Nup133 granules was quantified in (B), 5200 cells were analysed (mean ±SD, **P < 0.01; ***P < 0.001; N = 3).",
    "ncbi_link": "GFP: 
Nup133: 234865"
  },
  {
    "caption": "C-E HeLa cells stably expressing GFP-Nup107 were treated with the indicated siRNAs, synchronized by double thymidine block, released for 12 hours, treated with nocodazole to induce granule formation and washed-out as in (A) and analysed by live video spinning disk confocal microscopy. The selected frames of the movies are depicted and time is shown in minutes. The magnified framed regions are depicted in the lower rows. White arrowheads point to individual GFP-Nup107-positive granules. Yellow arrowheads point to the granules undergoing fusion events. The percentage of cells with fusion/fission events of GFP-Nup107 granules was quantified in (D), 815 cells were analysed (mean ±SD, **P < 0.01; N = 3). The number of fusion/fission events per cell was quantified in (E), 815 cells were analysed (mean ±SD; N = 3).",
    "ncbi_link": "GFP: 
Nup107: 57122"
  },
  {
    "caption": "H, I Mouse Embryonic Fibroblasts (MEFs) derived from the Fmr1 knock-out (KO) mice and wild type controls were synchronized in early G1 by Monastrol release and analysed by immunofluorescence microscopy (H). The percentage of cells with cytoplasmic nucleoporin granules was quantified in (I), 2400 cells were analysed (mean ±SD, *P < 0.05; N = 3).",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "A HeLa cells were transfected with the import/export reporter plasmid XRGG-GFP, treated with the indicated siRNAs and synchronized in early G1 phase by Monastrol release. Dexamethasone was added for 3 hours to induce XRGG-GFP nuclear import. Following wash-out the nuclear export of XRGG-GFP was analysed by live video spinning disk confocal microscopy. The selected frames of the movies are depicted in Figure EV5C. The percentage of cytoplasmic XRGG-GFP over time was quantified in Figure EV5D and quantifications of individual cells from the 20 and 30 minutes time points are depicted in (A), 199 cells were analysed (mean ±SD, *P < 0.05; **P < 0.01; N = 3).",
    "ncbi_link": "GFP: 
XRGG: "
  },
  {
    "caption": "B HeLa cells stably expressing GFP-Nup133 were treated with the indicated siRNAs, synchronized by double thymidine block, released for 12 hours and analysed by immunofluorescence microscopy. The magnified framed regions are shown in the corresponding numbered panels.",
    "ncbi_link": "GFP: 
Nup133: 234865"
  },
  {
    "caption": "(B) Relative miRNA  expression levels were quantified in  M238P cells treated for 72 h with BIBF1120 (BIBF, 2 μM), MAPKi (BRAFi, Vemurafenib and MEKi, Trametinib) (1µM), or with MAPKi (1 μM) plus BIBF (2 µM) by RT-qPCR  and normalized to miR-16-5p. Data is represented as mean ± SEM from a triplicate representative of 3 independent experiments. One-way ANOVA was used for statistical analysis. **P≤0.01, ***P≤0.001. Significance was calculated against the control group. Statistical significance of  BRAFi/MEKi vs BRAFi/MEKi + BIBF was also calculated. (C) Expression of miR-143-3p and miR-145-5p in control  mice  and mice  treated with the indicated therapies was quantified by RT-qPCR. Data is represented as mean ± SEM from 2 independent experiments performed on 6  mice, with 2 sites of injections. One-way ANOVA was used for statistical analysis. *P≤0.05, ****P≤0.0001. Significance was calculated against the control group. Statistical significance of BRAFi/MEKi vs  BRAFi/MEKi + BIBF was also calculated.",
    "ncbi_link": "miR-143-3p: 387161
miR-145-5p: 387163
miR-16-5p: 406951///406950"
  },
  {
    "caption": "(D) Relative miRNA expression levels was quantified in M238P cells stimulated for 48 h with TGF-β (10 ng/mL) or PDGF-BB (20 ng/mL) by RT-qPCR and normalized to miR-16-5p. Data is represented as mean ± SEM from a triplicate representative of 3 independent experiments. P-values were calculated using Paired Student t-test. *P≤0.05, ***P≤0.001. (E) Relative miRNA expression levels was quantified in M238R cells treated for 48 h with the triple kinase inhibitor Nintedanib/BIBF1120 (BIBF, 2 μM), the TGF-β receptor kinase inhibitor SB431542 (SB, 10 µM), and the pan-AKT inhibitor GSK690693 (GSK, 10 µM) by RT-qPCR. Data is represented as mean ± SEM from a triplicate representative of 3 independent experiments. P-values were calculated using Paired Student t-test. *P≤0.05, **P≤0.01, ***P≤0.001.",
    "ncbi_link": "miR-16-5p: 406951///406950"
  },
  {
    "caption": "(B) M238P cells were treated 72 h with BRAFi (Vemurafenib, 3 μM) in the presence or the absence of LNA-based anti-miR-143  (LNA-143) or anti-miR-145  (LNA-145) (50 nM) or a combination of the two. ECM markers RT-qPCR data is represented as mean ± SD from a triplicate representative of at least 3 independent experiments. One-way ANOVA was used for statistical analysis. *P≤0.05, **P≤0.01, ***P≤0.001.",
    "ncbi_link": "miR-143: 406935
miR-145: 406937"
  },
  {
    "caption": "(F)  Luciferase assay in HEK  cells overexpressing  miR-143 or miR-145  transfected with a plasmid harboring the WT or muted sequence of the miR-143 and miR-145 binding sites present in  FSCN1 3'UTR. Each bar represents the mean ± SE of experiments performed at least in triplicate. ***P≤0.001, ****P≤0.0001. P-values were calculated using Paired Student t-test.",
    "ncbi_link": "FSCN1: 6624
miR-143: 406935
miR-145: 406937"
  },
  {
    "caption": "(G)  RT-qPCR  analysis of  FSCN1 expression  in M238P cells transfected with the indicated mimics. Data is represented as mean ± SE from a triplicate representative of at least 3 independent experiments. Paired Student t-test was used for statistical analysis. ** P≤0.01, ***P≤0.001.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "(B) FSCN1 immunofluorescent staining  and quantification of fluorescence intensity in  M238P cells treated or not with BRAFi (Vemurafenib, 3 μM) in the presence or the absence of LNA-based anti-miR-143 (LNA-143) or anti-miR-145 (LNA-145) (50 nM) or a combination of the two. Data are represented as scatter plots with mean ± SD from 10 independent fields representative of 3 independent experiments, Mann-Whitney U test was used for statistical analysis. ****P≤0.0001. Scale bar 40 μm.",
    "ncbi_link": "miR-143: 406935
miR-145: 406937"
  },
  {
    "caption": "M238P cells were transfected with two different sequences of siRNAs vs FSCN1 or with a control siRNA (72 h, 100 nM). (D) Migration assay performed in Boyden chambers. Representative images showing migration of M238P cells treated with the indicated siRNAs. The bar graph represents the quantitative determination of data obtained of mean ± SD from 5 independent fields representative of 3 independent experiments, using ImageJ software. Paired Student t-test was used for statistical analysis. *P≤0.05, ***P≤0.001",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "M238P cells were transfected with two different sequences of siRNAs vs FSCN1  or with a control siRNA (72 h, 100 nM). (E) Western Blot analysis of phenotype-switch markers on cell lysates from  M238P cells transfected with the indicated siRNAs.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "BRAFi-resistant  M238R cells overexpressing FSCN1 were obtained after transduction with a  FSCN1 lentiviral construct. M238R transduced with a Ctrl lentivirus were used as control. (G) Western Blot  analysis of  FSCN1, phenotype switch markers and ECM remodeling markers on cell lysates from control and FSCN1 overexpressing cells.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "BRAFi-resistant M238R cells overexpressing FSCN1  were obtained after transduction with a FSCN1 lentiviral construct. M238R transduced with a Ctrl  lentivirus  were used as control. (H) Crystal violet viability assay  of M238R cells stably overexpressing  FSCN1  during 6 days with the indicated doses of the BRAFi Vemurafenib. Data is represented as mean ± SD from a triplicate representative of at least 3 independent experiments. Paired Student t-test was used for statistical analysis. ****P≤0.0001.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "(A, M238P cells were transfected with miR-143-3p, miR-145-5p or a control mimic (miR-neg) (72 h, 30 nM). (B, M238P cells were treated 72 h with BRAFi (Vemurafenib, 3 µM) or a combination of BRAFi (Vemurafenib, 0.5 µM) and MEKi (Trametinib, 1 µM). (A-B) Images and quantification of cell area in cells stained for  F-actin (red) and nuclei (blue). Data is represented as scatter plot with mean ± SD (n≥30 cells per condition). Mann-Whitney U test was used for statistical analysis. ****P≤0.0001. Scale bar 40 μm.",
    "ncbi_link": "miR-143-3p: 406935
miR-145-5p: 406937"
  },
  {
    "caption": "C) M238P cells were transfected with  miR-143-3p, miR-145-5p or a control mimic (miR-neg) (72 h, 30 nM). D) M238P cells were treated 72 h with BRAFi (Vemurafenib, 3 µM) or a combination of BRAFi (Vemurafenib, 0.5 µM) and MEKi (Trametinib, 1 µM). (C-D) Images and quantification of focal adhesions  number in cells stained  for pPaxillin (green) and nuclei  (blue). Focal adhesions (FA) number is represented as mean ± SD (n≥30 cells per condition). Each point represents the average number of  focal adhesions per cell calculated for each field. Paired Student t-test has been used for statistical analysis. *P≤0.01, ***P≤0.001, ****P. ≤0.0001. Scale bar 40 μm.",
    "ncbi_link": "miR-143-3p: 406935
miR-145-5p: 406937"
  },
  {
    "caption": "(E-F) M238P cells were transfected with two different sequences of siRNAs vs FSCN1 or with a control siRNA (72 h, 100 nM). (E) Images and quantification of cell area in cells stained  for  F-actin (red) and nuclei  (blue). Data is represented as scatter plot with mean ± SD (n≥30 cells per condition). Mann-Whitney U test was used for statistical analysis. ****P≤0.0001. Scale bar 40 μm. (F) Images and quantification of  focal adhesions (FA) number in cells  stained  for pPaxillin  (green) and nuclei  (blue). Focal adhesions number is represented as mean ± SD (n≥30 cells per condition). Each point represents the average number of focal adhesions per cell calculated for each field. Paired Student t-test was used for statistical analysis. ****P≤0.0001. Scale bar 40 μm.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "E) M238P cells were transfected with miR-143-3p, miR-145-5p or a control mimic (miR-neg) (72 h, 30 nM). (E) Effect of miR-143-3p or miR-145-5p overexpression on the  expression of YAP/MRTF target genes assessed by RT-qPCR. Data are normalized to the  expression in control cells. Data is represented as mean ± SD from a triplicate representative of at least 3 independent experiments. Paired Student t-test was used for statistical analysis. *P≤0.05, **P≤0.01, ****P≤0.0001.",
    "ncbi_link": "miR-143-3p: 406935
miR-145-5p: 406937"
  },
  {
    "caption": "M238P cells were transfected with two different sequences of siRNAs vs FSCN1  or with a control siRNA (72 h, 100 nM). Effect of FSCN1 downregulation on MRTFA (F) and YAP1 (G) nuclear translocation assessed by  immunofluorescence  in M238P. Data are represented as scatter plot with mean ± SD (n≥30 cells per condition). Each point represents the nuclear/cytoplasm ratio. Mann-Whitney U test was used for statistical analysis. ***P≤0.001, ****P≤0.0001. Scale bar 40 μm.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": "M238P cells were transfected with two different sequences of siRNAs vs  FSCN1 or with a control siRNA (72 h, 100 nM). (H) RT-qPCR  analysis for the expression of MRTFA/YAP target genes in M238P cells transfected with the indicated siRNAs. Data are normalized to the  expression in parental cells. Data is represented as mean ± SE from a triplicate representative of at least 3 independent experiments. Paired Student t-test was used for statistical analysis. *P≤0.05, **P≤0.01, ***P≤0.001. Scale bar 40 μm.",
    "ncbi_link": "FSCN1: 6624"
  },
  {
    "caption": " A) Treadmill analysis (n=8/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by unpaired, two-tailed Student's t test ***p=0.005; ***p=0.0007 (T3) and ****p<0.0001 (T4). Only p values for rapamycin-treated vs. untreated Cox15sm/sm mice are shown ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " B) Histological and histochemical characterization of skeletal muscle in rapamycin-treated and untreated Cox15sm/sm and WT mice. H&E: hematoxylin and eosin; PAS: periodic acid Schiff reaction; COX: cytochrome c oxidase; SDH: succinate dehydrogenase. White bars correspond to 50µm ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " C) Analysis of the cross-sectional area of muscle fibers in the different genotypes (n=3/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test: ***p=0.001; ***p=0.006, ****p<0.0001 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " D) Analysis of the number of centralized nuclei in muscle fibers (n=3/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test **p=0.0018, **p=0.0052 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " E) Analysis of PAS-reaction intensity in muscle fibers (n=4/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test *p=0.0293 (WT vs. Cox15sm/sm) and *p=0.0150 (Cox15sm/sm vs. Cox15sm/sm Rapa) ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " F) Analysis of COX-reaction intensity in muscle fibers (n=3). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test ****p<0.0001; **p=0.0031 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " G) Analysis of SDH-reaction intensity in muscle fibers (n=3). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test *p=0.0199, **p=0.0091 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " A) Spectrophotometric activities of the respiratory chain (n=4-5/group). CS: citrate synthase; CIV: complex IV. Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by two way ANOVA with Tukey's correction ****p<0.0001 (CS: WT vs. Cox15sm/sm), ***p=0.0010 (CS: Cox15sm/sm vs. Cox15sm/sm rapamycin), ****p<0.0001 (CIV: WT vs. Cox15sm/sm), **p=0.0060 (CIV/CS: WT vs. Cox15sm/sm) ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " B) Western blot immunovisualization of subunits of the respiratory complexes. Note the increased protein levels in Cox15sm/sm vs. WT samples, which are reduced to normal levels upon rapamycin treatment. Additional samples were run on a separate gel (not shown) ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " C) BNGE in gel activity for cIV. Sc: supercomplexes. Note that the COX reaction is slightly increased in rapamycin-treated vs. untreated Cox15sm/sm samples ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " D) Immunoblot of 1D-BNGE using an anti-cIV antibody (COX1). Note that COX amount is slightly increased in rapamycin treated vs. untreated Cox15sm/sm muscles. SDHB was used as a loading control ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " E) State III (succinate-driven) oxygen consumption (n=3/group). Error bars represent SEM. The asterisks represent the significance levels calculated by unpaired, two tail Student's t test **p=0.0016 (WT vs. Cox15sm/sm); *p=0.047 (Cox15sm/sm vs. Cox15sm/sm rapamycin) ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " Note the accumulation of profoundly altered mitochondria in Cox15sm/sm muscles (white arrows), possibly as a result of partially digested organelles within endolysosomes. Black arrows indicate examples of normal mitochondria. In rapamycin-treated Cox15sm/sm animals only a few of these structures are present, which can be detected also in rapamycin-treated WT samples. The bar corresponds to 1136 nm (4400X) ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " A) Representative western blot of autophagy markers at steady state in skeletal muscle. GAPDH was used as a loading control. B) Densitometric analysis of immunoblots similar to that shown in A (n=4/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test **p=0.0068 (LC3-II WT vs. Cox15sm/sm), **p=0.0063 (P62 WT vs. Cox15sm/sm) *p=0.025 (P62 Cox15sm/sm vs. Cox15sm/sm+rapamycin), **p=0.0098 (S6 WT vs. Cox15sm/sm), *p=0.034 (P-S6 WT vs WT+rapamycin), ***p=0.0002 (Cox15sm/sm vs. Cox15sm/sm+rapamycin), *p=0.014 (P-S6 WT vs. WT+rapamycin) ***p=0.0007 (Cox15sm/sm vs. Cox15sm/sm+rapamycin)",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " C) Analysis of the autophagic flux (n=3/group). Upper panel: representative western blot of Cox15sm/sm and WT muscles treated with colchicine, rapamycin, or rapamycin plus colchicine. Note that LC3-II was increased in Cox15sm/sm vs. WT samples. Colchicine did not increase LC3-II levels suggesting a block in the autophagic flux; rapamycin plus colchicine treated Cox15sm/sm mice showed higher levels of LC3-II, suggesting that rapamycin increased the autophagic flux in Cox15sm/sm muscles. Black: WT; dark grey: colchicine-treated WT; middle grey: rapamycin-treated WT; light grey: colchicine plus rapamycin treated mice; red: untreated Cox15sm/sm; orange: colchicine-treated; blue: rapamycin-treated Cox15sm/sm; purple: colchicine plus rapamycin treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test **p=0.0049 (WT vs. WT+colchicine), **p=0.0046 (WT+rapamycin vs. WT+rapamycin+colchicine), *p=0.0225 (WT vs. Cox15sm/sm), **p=0.0057 (Cox15sm/sm colchicine vs. Cox15sm/sm+rapamycin+colchicine), ***p=0.0003 (Cox15sm/sm rapamycin vs. Cox15sm/sm+rapamycin+colchicine)",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " A) Analysis of the autophagic flux (n=4/group). Upper panel: representative western blot of Cox15sm/sm and WT muscles treated with colchicine, rilmenidine, or rilmenidine plus colchicine. Colchicine alone increased LC3-II in WT but not Cox15sm/sm mice; rilmenidine had no effect on WT LC3-II levels, but reduced them in Cox15sm/sm mice. Rilmenidine plus colchicine increased LC3-II levels in both WT and Cox15sm/sm mice. Black: WT; dark grey: colchicine-treated WT; middle grey: rapamycin-treated WT; light grey: colchicine plus rapamycin treated mice; red: untreated Cox15sm/sm; orange: colchicine-treated; blue: rapamycin-treated Cox15sm/sm; purple: colchicine plus rapamycin treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test: **p=0.0093 (WT vs. WT+colchicine), ****p<0.0001 (WT+rilmenidine vs. WT+rilmenidine+colchicine), **p=0.0001 (WT vs. Cox15sm/sm), **p=0.0083 (Cox15sm/sm vs. Cox15sm/sm+rilmenidine), *p=0.0112 (Cox15sm/sm vs. Cox15sm/sm+rilmenidine+colchicine), ****p<0.000",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " B) Treadmill analysis (n=4/group). Black: untreated WT; grey: rilmenidine-treated WT; red: untreated Cox15sm/sm; blue: rilmenidine-treated Cox15sm/sm. Error bars represent SEM ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " C) Histological and histochemical characterization of skeletal muscle in rapamycin-treated and untreated Cox15sm/sm and WT mice. H&E: hematoxylin and eosin; GT: Gomori trichrome; PAS: periodic acid Schiff reaction ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " D) Analysis of the cross-sectional area of muscle fibers in the different genotypes (n=3/group). Black: untreated WT; grey: rilmenidine-treated WT; red: untreated Cox15sm/sm; blue: rilmenidine-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test ***p=0.0002, ****p<0.0001 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " E) Analysis of the number of centralized nuclei in muscle fibres (n=3/group). Black: untreated WT; grey: rilmenidine-treated WT; red: untreated Cox15sm/sm; blue: rilmenidine-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test **p=0.0091 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " A) anti-TFEB immunofluorescence on rapamycin- and rilmenidine-treated WT and Cox15sm/sm muscles vs. untreated (UT) samples. CD11C (blue signal) indicates inflammatory cells. Right panel: quantification of n=3 animals/group. The scale bars correspond to 30µm. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test B) Quantification of the TFEB-positive nuclei (n=3/group). Quantification was performed using Imaris spots surface excluding the CD11C positive nuclei. Error bars represent SEM. The asterisks represent the significance levels calculated by one-way ANOVA with Tukey post-hoc multiple comparison test *p=0.0199 (WT vs. WT+rapamycin), *p=0.0150 (Cox15sm/sm vs. Cox15sm/sm+rapamycin), ***p=0.0001 ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": " A) Real-time PCR analysis of Lamp1 transcript (n=3/group). Black: untreated WT; grey: rapamycin-treated WT; red: untreated Cox15sm/sm; blue: rapamycin-treated Cox15sm/sm. Error bars represent SEM. The asterisks represent the significance levels calculated by Student's t test **p=0.008, *p=0.038 ",
    "ncbi_link": "Cox15: 226139
Lamp1: 16783"
  },
  {
    "caption": " B) Anti-LAMP1 staining in rapamycin- and rilmenidine-treated WT and Cox15sm/sm muscles vs. untreated (UT) samples. Rapamycin, but not rilmendine, increases the number of LAMP1-positive vesicles in Cox15sm/sm samples (inset). The scale bars correspond to 30µm ",
    "ncbi_link": "Cox15: 226139"
  },
  {
    "caption": "D. mRNA expression  of PGF2α  synthases in the retinas  of OIR mice  during postnatal days 12-17 (n= E. mRNA expression  of Ptgfr  in the retinas  of OIR mice  during postnatal days 12-17 (n=6-8). Data information: n.s. stands for \"not significant.\" Data were analyzed by , two-way ANOVA with Tukey's multiple comparisons test D, E, Data are represented as mean ± SEM.",
    "ncbi_link": "Ptgfr: 19220"
  },
  {
    "caption": "F. mRNA expression  of Ptgfr  in each retinal  layer  from normoxic and OIR mice  on postnatal day 16 (n=6). The left-hand image displays representative cross-sections from OIR and normoxic retinas, with  isolectin B4-stained vessels  in green, DAPI-stained nuclei  in blue, and LCM  isolation locations circled by white dashed circles. INL,  inner nuclear layer; ONL, outer nuclear layer; RGC,  retinal ganglion cells. Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test F) Scale bar: 20 μm. Data are represented as mean ± SEM.",
    "ncbi_link": "Ptgfr: 19220"
  },
  {
    "caption": "G. Ptgfr  mRNA expression  in retinal endothelial cells  (CD31+CD45-) sorted by MACS from normoxic and OIR mice  on postnatal day 16 (n=5). Data information: n.s. stands for \"not significant.\" Data were analyzed Mann-Whitney test (G). Scale bar: 20 μm. Data are represented as mean ± SEM.",
    "ncbi_link": "Ptgfr: 19220"
  },
  {
    "caption": "B. Ptgfr  mRNA levels in retinal microvessels   of CKO-T and control mice  (n=6). INL,  inner nuclear layer; ONL, outer nuclear layer; RGC, retinal ganglion cells. Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test (B, Data are represented as mean ± SEM.",
    "ncbi_link": "Ptgfr: 19220"
  },
  {
    "caption": "D. Effect of PTGFR  deficiency in ECs  on ELR+ CXC chemokine expression  in retinas  from OIR mice  on postnatal day 16 (n=6). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test image).Data are represented as mean ± SEM.",
    "ncbi_link": "PTGFR: 19220"
  },
  {
    "caption": "F. Retinal CXCL1 protein-expression levels in Cxcl1-expressing lentivirus-injected CKO mice  (n=3). G. Quantitation of retinal CXCL1  protein in F (n=3). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test G, image).Data are represented as mean ± SEM.",
    "ncbi_link": "Cxcl1: 14825"
  },
  {
    "caption": "H. Representative images of oxygen-induced retinal angiogenesis   in Cxcl1-expressing lentivirus-injected CKO mice  on postnatal day 17. Green represents the isolectin B4-stained vessels, the second-row panels display the enlarged images of white boxes in the first-row panels, the third-row images show  neovascular tufts (NV, white), and the fourth-row images show the vaso-obliteration (VO, white) area. I. Quantitation of oxygen-induced retinal neovascularization  in H (n=8). J. Quantitation of retinal vaso-obliteration  in H (n=8). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test , I, J). Scale bar: 500 μm (H, unmagnified image), 150 μm (H, magnified image).Data are represented as mean ± SEM.",
    "ncbi_link": "Cxcl1: 14825"
  },
  {
    "caption": "B. Relative expression  levels of FOS  in  retinal microvascular ECs from patients  with PDR  (n=4) compared with the corresponding expression  levels from normal subjects (n=7) (Gene Expression Omnibus Database dataset GSE94019). TPM stands for \"Transcripts per kilobase million.\" Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test (B, Data in B are expressed as the mean + SD.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "C. Effect of FOS  knockdown on 500 nM PGF2α-induced CXCL8 expression  in HRMECs  (n=4). D. Effect of FOS  knockdown on 500 nM PGF2α-induced HRMEC CXCL8  secretion in the culture medium (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test C, D, Data in C, D, are represented as mean ± SEM. ",
    "ncbi_link": "CXCL8: 3576
FOS: 2353"
  },
  {
    "caption": "E. and F. Effect of RA  (1 μM, AP-1  dimer inhibitor), SN-50  (100 μg/mL, NFκB  inhibitor), and  Inca-6  (2.5 μM, NFAT  inhibitor) on 500 nM PGF2α-induced CXCL8 expression  in HRMECs and HRMEC CXCL8  secretion in the culture medium (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test E, F, Data in E, F, are represented as mean ± SEM. ",
    "ncbi_link": "CXCL8: 3576"
  },
  {
    "caption": "G. Representative images of scratch-induced migration  of 500 nM PGF2α-treated HRMECs  with or without FOS  knockdown. The yellow solid line indicates the original position of the scratch, the dashed line indicates the position of the cells after migration, and the arrows represent the migratory direction. H. Quantitation of the cell-migration  distance in H (n=4). I. Effect of FOS  knockdown on 500 nM PGF2α-induced HRMEC proliferation  (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test (H, I Scale bar: 100 μm (G) Data in H, I, are represented as mean ± SEM. ",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "J. Representative images of tube  formation by 500 nM PGF2α-treated HRMECs  with or without FOS  knockdown. K. Quantitation of total tube  length, number of junctions, number of meshes, and percentage of mesh area in J (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test K, Scale bar: 200 μm (J, Data in K, are represented as mean ± SEM. ",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "L. Fos  mRNA levels in retinas  from OIR mice during postnatal days 12-17 (n=3-4). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test L, Data in , L, are represented as mean ± SEM. ",
    "ncbi_link": "Fos: 14281"
  },
  {
    "caption": "M. Effect of PTGFR  deficiency in ECs  on Fos expression  in the retina  from OIR mice  on postnatal day 16 (n=6). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test M, Data in M, are represented as mean ± SEM. ",
    "ncbi_link": "Fos: 14281
PTGFR: 19220"
  },
  {
    "caption": "B. Effect of U73122  (10 μM), BAPTA  (50 μM), Y27632  (5 μM), and Ly294002  (15 μM) treatment on 500 nM PGF2α-induced FOS gene expression in HRMECs  (n=4). C. Effect of KN93  (10 μM) and RO-318220 (250 nM) treatment on 500 nM PGF2α-induced FOS expression  in HRMECs  (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test (B, C Data are represented as mean ± SEM.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "D. Effect of SB203580  (2 μM), PD98059  (20 μM), and SP600125  (60 nM) treatment on 500 nM PGF2α-induced FOS gene expression in HRMECs  (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test Data are represented as mean ± SEM.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "J. Effect of CAMK2G  or CAMK2D  knockdown on 500 nM PGF2α-triggered p38 phosphorylation  in HRMECs. K. Quantitation of the ratio of p38 phosphorylation  to total p38  protein in J (n=3). Data information: n.s. stands for \"not significant.\" Data were analyzed by unpaired student's t-test Data are represented as mean ± SEM.",
    "ncbi_link": "CAMK2D: 817
CAMK2G: 818"
  },
  {
    "caption": "L. Effect of CAMK2G  or CAMK2D  knockdown on 500 nM PGF2α-induced FOS expression  in HRMECs  (n=4). Data information: n.s. stands for \"not significant.\" Data were analyzed by Mann-Whitney test L) Data are represented as mean ± SEM.",
    "ncbi_link": "CAMK2D: 817
CAMK2G: 818
FOS: 2353"
  },
  {
    "caption": "B. Representative images of OIR retinas  in WT and Cxcr2-/- mice  with or without AL8810  treatment. The green color shows the  isolectin B4-stained vessels, the second-row panels display the enlarged images of white boxes in the first-row panels, the third-row images show  neovascular tufts (NV, white), and the fourth-row images show the  vaso-obliteration (VO, white) area. C. Quantitation of oxygen-induced retinal neovascularization  in WT and Cxcr2-/- mice  with or without AL8810  treatment (n=12). D. Quantitation of retinal vaso-obliteration in WT and Cxcr2-/- mice  with or without AL8810  treatment (n=12). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Tukey's multiple comparisons test (C, D) Scale bar: 500 μm (unmagnified image), 150 μm (magnified image). Data are represented as mean ± SEM.",
    "ncbi_link": "Cxcr2: 12765"
  },
  {
    "caption": "E. Effect of AL8810  on retinal Fos expression  in WT and Cxcr2-/- OIR mice  on postnatal day 16 (n=6). F. Effect of AL8810  on retinal Cxcl1 expression  in WT and Cxcr2-/- OIR mice  on postnatal day 16 (n=6). Data information: n.s. stands for \"not significant.\" Data were analyzed by two-way ANOVA with Mann-Whitney test (E, F). Data are represented as mean ± SEM.",
    "ncbi_link": "Cxcl1: 14825
Cxcr2: 12765
Fos: 14281"
  },
  {
    "caption": " A Neonatal rat ventricular myocytes (NRVMs) were infected with the 3xMEF2-Luc reporter, serum starved for 20 hours and stimulated for 24 hours with different agonists: 100 nM endothelin-1 (ET1), 1 μM sphingosine-1-phosphate (S1P), 10 μM lisophosphatidic acid (LPA), 1 μM WIN55,212-2 (WIN55, cannabinoid receptor agonist), 1 μM isoproterenol (ISO, β-adrenergic receptor agonist), 100 nM angiotensin II (AngII), 10 μM prostaglandin E1 (PGE1), 10 μM prostaglandin E2 (PGE2) or 100 nM prostanoid F receptor agonist fluprostenol (Flupro), 100 nM treprostinil (Trepro, prostacyclin receptor agonist) Data information: values are mean±s.e.m. In (A), the experiment was performed in triplicates, similar results were obtained in 3 different experiments. Student's two-tailed t-test, *,P<0.05 vs. control (ET1, P=0.0013; S1P, P=0.0144; LPA, P=0.026; WIN55, P=0.6205; ISO=0.0399; AngII, P=0.5812; PGE1, P=0.001; PGE2, P<0.0001; Flupro, P=0.0846; Trepro, P=0.1958) ",
    "ncbi_link": "MEF2: 498607///81518///309957///499497"
  },
  {
    "caption": " B PGE2 induces the expression of MEF2 target genes. NRVMs were serum-starved for 24 hours, then were stimulated with 1 μM PGE2 for 2 hours and mRNA levels of the indicated genes were determined Data information: values are mean±s.e.m In (B), n=5, technical replicates, Student's two-tailed t-test, *,P<0.05 vs. control (Nur77, P=0.0148; Myomaxin, P=0.0417; Adamts1, P=0.0112; BNP, P=0.0065)",
    "ncbi_link": "Adamts1: 79252
BNP: 25105
Nur77: 79240
Myomaxin: 311098"
  },
  {
    "caption": " D, PGE2 activates MEF2 via EP3 receptor. NRVMs were infected with the 3xMEF2-Luc reporter and serum-starved for 20 hours. The cells were stimulated with DMSO or 1 μM PGE2 for 24 hours in the presence or absence of different EP receptor antagonists: AH6809 (10 μM, EP1- and EP2-antagonist) or 798106 (200 nM, EP3-antagonist) or L161,982 (2 μM, EP4-antagonist) Data information: values are mean±s.e.m In (D), n=3, independent experiments, * represents significant interaction between the two treatments (P<0.05, Two-Way ANOVA, AH6809, P=0.1092; L798106, P=0.0002; L161,982, P=0.5579). The exact n and P values can be also found in the Source Data excel file for Figure 1",
    "ncbi_link": "MEF2: 498607///81518///309957///499497"
  },
  {
    "caption": " B-D (B, D) NRVMs were infected with the 3xMEF2-Luciferase reporter and with recombinant adenoviruses encoding EGFP (AdGFP), RGS16, RGS2, p63ΔN, RGS-LSCII, or Gαt, as indicated. The cells were serum starved for 20 hours and stimulated with DMSO or 1 μM PGE2 for 24 hours. (C) NRVMs were infected with the 3xMEF2-Luciferase reporter and pretreated with the adenylyl cyclase inhibitor SQ22536 (100 μM) for 20 minutes or the Gi/o-protein inhibitor pertussis toxin (PTX, 100 ng/ml) for 20 hours in serum-starved conditions and treated with DMSO or 1 μM PGE2 for 24 hours. Data information: In (B-D), n=3, independent experiments, * represents significant interaction between the two treatments (P<0.05, Two-Way ANOVA, RGS16, P<0.0001; RGS2, P=0.1725; p63ΔN, P=0.0666; RGS-LSCII, P=0.0818, SQ22536, P=0,385; PTX, P<0.0001; Gαt, P<0,0001), values are mean±s.e.m. The exact n and P values can be also found in the Source Data excel file for Figure 2 ",
    "ncbi_link": "Gαt: 
RGS-LSCII: 
RGS16: 360857
RGS2: 84583
p63: 246334"
  },
  {
    "caption": " A,B NRVMs were infected with recombinant adenovirus encoding Flag-HDAC5 (A) or not infected (B) and serum starved for 20 hours. The cells were pretreated with the PKC-inhibitor bisindolylmaleimide I (2 μM) or the PKD-inhibitor BPKDi (3 μM) for 20 minutes and stimulated with 100 nM endothelin-1 (ET1) or 100 μM phenylephrine (PE) or 1 μM PGE2 for 4 hours, as indicated. HDAC phosphorylation was detected by immunoblotting with the anti-HDAC5 phospho-Ser-498 antibody, phosphorylation of PKD was assessed using anti-phospho-PKD antibodies (Ser-744/Ser-748 and Ser-916), representative images are shown from 3 independent experiments ",
    "ncbi_link": "HDAC5: 84580"
  },
  {
    "caption": " B NRVMs were infected with recombinant adenoviruses encoding EGFP (AdGFP) or RGS16 24 hours prior to stimulation, then Rac1 activity was measure Data information: In (A-C) representative images from at least 3 independent experiments are shown. In (B-D) values are mean±s.e.m., (B,C) n=4 3; *,P<0.05 (Two-Way ANOVA, RGS16, P=0.0415 (B ), NSC effect on Rac1 activation, P=0.0412 (C); NSC effect on MEF2 induction, P<0.0001. PGE2 effect was significant in Rac1 activation, P<0.0001). The exact n and P values can be also found in the Source Data excel file for Figure 4",
    "ncbi_link": "RGS16: 360857"
  },
  {
    "caption": " B After infection with Flag-HDAC5 and serum starvation, NRVMs were treated with 50 μM NSC23766 for 2 hours prior to stimulation. The cells were stimulated with 1 μM PGE2 for 1 hour. HDAC5 phosphorylation at Ser-498 was detected by immunoblot. The phosphorylation of HDAC5 at this site was not prevented by NSC Data information: In (A-C) representative images from 3 independent experiments are shown ",
    "ncbi_link": "HDAC5: 84580"
  },
  {
    "caption": " D MEF2 activity was determined in cells infected with the 3xMEF2-Luc reporter after serum starvation. Cells were stimulated with vehicle or 1 μM PGE2 for 24 hours after 1-hour of 30 μM IPA-3 pretreatment. IPA-3 inhibited the MEF2 activation by PGE2 Data information In (D) values are mean±s.e.m., n=3, biological replicates, *,P<0.05 (two-way ANOVA, P<0.0001). The exact n and P values can be also found in the Source Data excel file for Figure 5",
    "ncbi_link": "MEF2: 498607///81518///309957///499497"
  },
  {
    "caption": " Top: GFP-HDAC5 infected NRVMs were serum-starved for a day, pretreated for two hours with the indicated compounds (BPKDi, 3 µM, IPA-3, 30 µM) alone or in combination, then were stimulated for 4 hours. Representative images. Scale bar is 10 µm. Bottom : Statistical analysis of cellular localization of HDAC5. GFP-HDAC5 localization (nuclear or cytosolic) was assessed in >100 cells of each sample (n=3, technical replicates). *, P<0,05 (one-way ANOVA with Bonferroni post-hoc test, vehicle vs. ET1 or vs. PGE2, P<0.0001; PGE2 vs. PGE2+BPKDi, P=0.0004; PGE2 vs. PGE2+BPKDi, P=0.0114; PGE2 vs. PGE2+BPKDi+IPA-3, P<0.0001). The exact n and P values can be also found in the Source Data excel file for Figure 6 ",
    "ncbi_link": "HDAC5: 84580"
  },
  {
    "caption": " MEF2-lacZ reporter mice (BALB/c-background, 6-12 weeks old) were treated with 7 mg/kg lipopolysaccharide from Escherichia coli (O111:B4) or saline intraperitoneally and were sacrificed after 24 hours A mRNA-levels of different inflammatory cytokines, as indicated. The graphs show relative mRNA-levels, fold increase compared to saline-treated controls, normalized to 18s-content Data information: values are mean±s.e.m. The exact n values are shown in the bottom of the bar graphs. *,P<0.05, Welch's two-tailed unpaired t-test was used for statistical analysis, n.s.=not significant P values: IL6, P=0.0007 (A); TNFα, P<0.0001 (A)",
    "ncbi_link": "lacZ: 
IL6: 16193
MEF2: 17876
18s: 19791
TNFα: 21926"
  },
  {
    "caption": " MEF2-lacZ reporter mice (BALB/c-background, 6-12 weeks old) were treated with 7 mg/kg lipopolysaccharide from Escherichia coli (O111:B4) or saline intraperitoneally and were sacrificed after 24 hours B PGE2 was quantified after mechanical homogenization of deeply frozen hearts using nano-liquid chromatography tandem mass spectrometry Data information: values are mean±s.e.m. The exact n values are shown in the bottom of the bar graphs. *,P<0.05, Welch's two-tailed unpaired t-test was used for statistical analysis, n.s.=not significant P values PGE2, P=0.0016 (B",
    "ncbi_link": "lacZ: 
MEF2: 17876"
  },
  {
    "caption": " MEF2-lacZ reporter mice (BALB/c-background, 6-12 weeks old) were treated with 7 mg/kg lipopolysaccharide from Escherichia coli (O111:B4) or saline intraperitoneally and were sacrificed after 24 hours C Histologic and macroscopic stainings of β-galactosidase-activity in MEF2-lacZ reporter mice show MEF2-activation (blue cells and precipitates, respectively) in the myocardium upon LPS-treatment. Saline-treated littermates served as control. Scale bar of histological stainings is 100 µm. Quantification of whole-heart stainings is shown in the right panel (pixel intensity in blue channel normalized to total intensity) Data information: values are mean±s.e.m. The exact n values are shown in the bottom of the bar graphs. *,P<0.05, Welch's two-tailed unpaired t-test was used for statistical analysis, n.s.=not significant. In (C) representative images of myocardial sections are shown from 3 independent experiments and representative whole hearts of 6 independent experiments. P values blue pixel intensity, P=0.0083 (C)",
    "ncbi_link": "lacZ: 
MEF2: 17876"
  },
  {
    "caption": " MEF2-lacZ reporter mice (BALB/c-background, 6-12 weeks old) were treated with 7 mg/kg lipopolysaccharide from Escherichia coli (O111:B4) or saline intraperitoneally and were sacrificed after 24 hours D Induction of PKD, HDAC5 and PAK2 in myocardial inflammations. Immunoblots were performed on extracts of hearts of saline- and LPS-treated mice. Representative blots are shown in the left panel, the quantification is in the right panel Data information: values are mean±s.e.m The exact n values are shown in the bottom of the bar graphs. *,P<0.05, Welch's two-tailed unpaired t-test was used for statistical analysis, n.s.=not significant P values ); phospho-PKD-Ser-744/Ser-748, P=0.0049 (D); phospho-PKD-Ser-916, P=0.2684 (D); phospho-HDAC5-Ser-498 (D), P=0.0019; phospho-HDAC5-Ser-259, P=0.0003 (D); phospho-PAK2-Ser-192/Ser-197, P=0.1962 (D); phospho-PAK2-Thr-402, P=0.0446 (D). The exact n and P values can be also found in the Source Data excel file for Figure 7",
    "ncbi_link": "lacZ: 
MEF2: 17876"
  },
  {
    "caption": "(C) Relative mRNA expression from real-time PCR analysis of the GnRH transcript in GFP-positive cells, in comparison with GFP-negative cells. The GnRH transcript appears to be selectively expressed in GFP-positive cells. Mann-Whitney U test, n=4 mice from 2 litters.",
    "ncbi_link": "GnRH: 14714"
  },
  {
    "caption": "(D) Relative mRNA expression from real-time PCR analysis of Neuropilin-1 (Nrp1), Nrp2, Plexin A1 (PlxnA1), and PlxnA4 transcripts in FACS-isolated GFP-positive GnRH neurons from control (Nrp1loxP/loxP; grey) and mutant (Gnrh::cre; Nrp1loxP/loxP; red) P0 mice. Unpaired t-test, n=5 to 6 mice per group from 3 litters.",
    "ncbi_link": "GFP: 
cre: 2777477
Gnrh: 14714
Neuropilin-1: 18186
Nrp1: 18186
Nrp2: 18187
Plexin A1: 18844
PlxnA1: 18844
PlxnA4: 243743"
  },
  {
    "caption": "(E) Representative immunofluorescence images showing GnRH neurons migrating along Nrp1-immunoreactive vomeronasal/terminal nerve fibers (empty arrowheads) at the nose-brain junction in sagittal slices from E14.5 control and mutant embryos. GnRH neurons (green) themselves express Nrp1 (red, white arrows) in control Nrp1loxP/loxP mice whereas Nrp1 is undetectable in GnRH neurons from mutant Gnrh::cre; Nrp1loxP/loxP littermates (black arrows). Scale bar: 50μm.",
    "ncbi_link": "cre: 2777477
Gnrh: 14714
Nrp1: 18186"
  },
  {
    "caption": "(D) Representative image of cleared brains and immunolabeling for GnRH at the level of the olfactory bulbs, in a control (left panel) and a mutant (right panel) postnatal brain. Knock-out animals show an accumulation of GnRH neurons in the accessory olfactory bulb (circle formed by the GnRH labelling, right panel). AOB, accessory olfactory bulb. Scale bar: 300μm.",
    "ncbi_link": "GnRH: 14714"
  },
  {
    "caption": "Wild-type and LGP2-KO HEK293  cells in 24-well plates were transfected with 200 ng/ml of short poly I:C IFN-β  and IP-10  mRNA expression was determined by RT-qPCR. The data represent the mean ± SD (n = 3, t-test, *p < 0.05). LGP2  KO2 and KO3 are independently isolated LGP2  KO clones. Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "IP-10: 3627
LGP2: 79132
IFN-β: 3456"
  },
  {
    "caption": "Wild-type and LGP2-KO HEK293  cells in 24-well plates were infected with SeV. IFN-β and IP-10 mRNA expression was determined by RT-qPCR. The data represent the mean ± SD (n = 3, t-test, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "IP-10: 3627
LGP2: 79132
IFN-β: 3456"
  },
  {
    "caption": "(F) HEK293   cells in 24-well plates were transfected with LGP2    (0.1, 0.3, or 0.6 μg/well) and RIG-I (0.1 μg/well) expression vectors as indicated. 24 h after transfection, cells were stimulated with 200 ng of short poly I:C  for 4 hr. Total RNAs were extracted, and the expression of  IFN-β mRNA was determined by RT-qPCR   and normalized to GAPDH   (n = 3, t-test, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
GAPDH: 2597
IFN-β: 3456
RIG-I: 23586"
  },
  {
    "caption": "(G) HEK293FT  cells were transfected with FLAG-tagged LGP2  and HA-tagged ubiquitin    expression vectors. Whole cell extracts (WCE) were prepared 24 h after transfection. Immunoprecipitation  was performed with anti-FLAG  antibody (IP: FLAG) and the proteins were detected by western blot analysis with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HA: 
ubiquitin: 
LGP2: 79132"
  },
  {
    "caption": "(H) FLAG-tagged LGP2  was transfected into HEK293  cells. Cells were then infected with SeV  at MOI = 10 for 24 h. Immunoprecipitation  was performed with anti-FLAG  antibody, and the proteins were detected with the indicated antibodies.",
    "ncbi_link": "FLAG: 
LGP2: 79132"
  },
  {
    "caption": "A) HEK293  cells were transfected with FLAG-RIG-I  or FLAG-LGP2  expressing vector. Cells were then infected with SeV, and whole cell extracts were collected at indicated time points. Immunoprecipitation  was performed with anti-FLAG  antibody. The proteins were subjected to SDS-PAGE and detected by western blotting.",
    "ncbi_link": "FLAG: 
LGP2: 79132
RIG-I: 23586"
  },
  {
    "caption": "B) A549  cells transfected with HA-tagged ubiquitin  were stimulated with 200 ng/ml of short poly I:C for 6 h. PLA  was performed with anti-HA, anti-RIG-I, and anti-LGP2  antibodies. The number of PLA  signals were counted (t-test, *p < 0.05, n = 20). Each dot represents the number of PLA  signals of each cell. Data information: Scale bars represent 10 μm. All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "C) HEK293  cells were transfected with empty and LGP2  expression vectors for 24 hr. PLA  was performed with anti-LGP2  and anti-K63-Ub  antibodies. The number of PLA  signals were counted (t-test, *p < 0.05, n = 33). Each dot represents the number of PLA  signals of each cell. Data information: Scale bars represent 10 μm. All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132"
  },
  {
    "caption": "A) HEK293FT  cells were transfected with FLAG-tagged LGP2  and HA-tagged Riplet  expression vectors. 24 h after transfection, cells were lysed, and WCE were prepared. Immunoprecipitation  was performed with anti-FLAG  antibody, and the proteins were detected by  western blotting  with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HA: 
LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "B) HEK293FT  cells were transfected with FLAG-tagged LGP2  expression vector. 24 h after transfection, immunoprecipitation  was performed with anti-FLAG  antibody and control IgG. Immunoprecipitates  were subjected to  SDS-PAGE, and the proteins were detected by western blotting  with indicated antibodies.",
    "ncbi_link": "FLAG: 
LGP2: 79132"
  },
  {
    "caption": "C) HEK293FT  cells were transfected with FLAG-tagged LGP2, Riplet, and HA-tagged ubiquitin  expression vectors, and immunoprecipitation  was performed with anti-FLAG  antibody.",
    "ncbi_link": "FLAG: 
HA: 
LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "D) HEK293FT  cells were transfected with FLAG-tagged LGP2, Riplet, and myc-tagged K63-only-Ub  expression vectors. 24 h after transfection, immunoprecipitation  was performed with anti-FLAG  antibody.",
    "ncbi_link": "FLAG: 
myc: 
LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "E) WT and Riplet  KO HEK293  cells were transfected with FLAG-tagged LGP2  and myc-tagged K63-only-Ub  expression vectors, and immunoprecipitation  was performed with anti-FLAG  antibody.",
    "ncbi_link": "FLAG: 
myc: 
LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "(F, G) WT and Riplet  KO HEK293  cells were transfected with 200 ng/ml of short poly I:C for 6 h, and PLA  was performed with anti-LGP2  and anti-K63-Ub  antibodies. The number of PLA  signals were counted (t-test, *p < 0.05, n = 100). Each dot represents the number of PLA  signals in each cell. Scale bars represent 10 μm. Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "Riplet: 84282"
  },
  {
    "caption": "(A) Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of LGP2  in Riplet-expressing cells. LC-MS/MS data was quantified using LFQ method. The chromatographic profiles for each ubiquitination  site are shown in the right panels. Schematic representation of ubiquitination  sites of RIG-I  and LGP2  are shown in the upper panel.",
    "ncbi_link": "Riplet: 84282"
  },
  {
    "caption": "(B) FLAG-tagged LGP2  fragments and HA-tagged Riplet  expression vectors were transfected into HEK293FT  cells. 24 h after transfection WCE were prepared. immunoprecipitation  was performed with anti-FLAG  antibody. Immunoprecipitates  were subjected to  SDS-PAGE, and the proteins were detected by western blotting with indicated antibodies. The data is a representative of two independent experiments.",
    "ncbi_link": "FLAG: 
HA: 
LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "(C) FLAG-tagged LGP2  and FLAG-tagged LGP2-4KR expression vectors were transfected into HEK293FT  cells. 24 h after transfection, WCE were prepared. Immunoprecipitation  was performed with anti-FLAG  antibody. The data is a representative of two independent experiments.",
    "ncbi_link": "FLAG: 
LGP2: 79132"
  },
  {
    "caption": "(A) RIG-I, WT LGP2, and KR mutants of LGP2  were transfected into HEK293  cells together with p125luc reporter plasmids.  Luciferase activities were determined 24 h after transfection. The data represent the mean ± SD (n = 3, t-test, *p < 0.05). WCEs were subjected to  SDS-PAGE, and the proteins were detected by  western blotting (lower panels). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "luc: 
LGP2: 79132
RIG-I: 23586"
  },
  {
    "caption": "(B) HE293  cells stably expressing GFP  (control), LGP2, or LGP2-4KR were transfected with p125luc reporter plasmids and then stimulated with indicated amounts of short poly I:C. WCEs were prepared 24 h after transfection and stimulation, and luciferase activity  was determined. The proteins were subjected to  SDS-PAGE and detected by western blotting with the indicated Abs. The data represent the mean ± SD (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "GFP: 
luc: 
LGP2: 79132"
  },
  {
    "caption": "HEK293  cells stably expressing GFP, LGP2, or LGP2-4KR were transfected with 200 ng/ml of short poly I:C  (C-E), Total RNA was isolated at the indicated time points. The expression of IFN-β, IP-10, and Ccl5  mRNA was determined by RT-qPCR  and normalized to GAPDH. The data represent the mean ± SD (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "GFP: 
Ccl5: 6352
IP-10: 3627
LGP2: 79132
GAPDH: 2597
IFN-β: 3456"
  },
  {
    "caption": "HEK293  cells stably expressing LGP2, or LGP2-4KR were infected with SeV  at MOI = 5 (F-H), Total RNA was isolated at the indicated  time points. The expression of IFN-β, IP-10, and Ccl5  mRNA was determined by RT-qPCR  and normalized to GAPDH. The data represent the mean ± SD (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "Ccl5: 6352
IP-10: 3627
LGP2: 79132
GAPDH: 2597
IFN-β: 3456"
  },
  {
    "caption": "HEK293  cells stably expressing LGP2, or LGP2-4KR were infected with influenza A virus (Flu) at MOI =10 (I, J). Total RNA was isolated at the indicated  time points. The expression of IFN-β, IP-10 mRNA was determined by RT-qPCR and normalized to GAPDH. The data represent the mean ± SD (n = 3, two-way ANOVA, *p < 0.05 Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "IP-10: 3627
LGP2: 79132
GAPDH: 2597
IFN-β: 3456"
  },
  {
    "caption": "(K, L) HEK293  cell clones stably expressing LGP2  or LGP2-4KR at lower levels were transfected with short poly I:C, and the expression of mRNAs were determined by RT-qPCR. The data represent the mean ± SD (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132"
  },
  {
    "caption": "A) Microarray  analysis was performed as described in materials and methods. A heatmap of the microarray  data of LGP2  and LGP2-4KR stably expressing cells stimulated with short poly I:C  for 12 h.",
    "ncbi_link": "LGP2: 79132"
  },
  {
    "caption": "B, LGP2  and LGP2-4KR stably expressing HEK293  cells were stimulated with 200 ng/ml of short  poly I:C, and the expression of the genes at the indicated  time points were determined by  RT-qPCR and normalized to GAPDH  (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
GAPDH: 2597"
  },
  {
    "caption": "C) LGP2  and LGP2-4KR stably expressing HEK293  cells were stimulated with 200 ng/ml of short poly I:C, and the expression of the genes at the indicated time points were determined by RT-qPCR  and normalized to GAPDH  (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
GAPDH: 2597"
  },
  {
    "caption": "LGP2  and LGP2-4KR stably expressing A549  cells were infected with influenza A virus (Flu) at MOI = 10, and the expression of the genes at the indicated  time points were determined by RT-qPCR and normalized to GAPDH  (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
GAPDH: 2597"
  },
  {
    "caption": "LGP2  and LGP2-4KR stably expressing A549  cells were infected with  influenza A virus  (Flu) at MOI = 10, and the expression of the genes at the indicated  time points were determined by  RT-qPCR and normalized to GAPDH  (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
GAPDH: 2597"
  },
  {
    "caption": "J, K) LGP2  and LGP2-4KR expressing vectors were transected into HeLa  cells with Riplet  expressing vector. 18 hr after transfection, cells were fixed, and then the PLA  signals of LGP2  and endogenous MAVS  were detected. Peroxisome  was visualized using CellLight Peroxisome-GFP  reagent. Colocalization  of GFP  (peroxisome) and the PLA  signals (red) were observed by confocal microscopy. Scale bars represent 10 μm (J). The colocalization  area was normalized to the area of the PLA  signals (n = 25, t-test, *p < 0.05) (K). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
Riplet: 84282"
  },
  {
    "caption": "WT, and Riplet   KO HEK293  cells were stimulated with 200 ng/ml of short poly I:C. The expression of SP100, PML, and ANKRD1  mRNA was determined by RT-qPCR  and normalized to GAPDH  (n = 3, two-way ANOVA, *p <0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "ANKRD1: 27063
GAPDH: 2597
PML: 5371
Riplet: 84282
SP100: 6672"
  },
  {
    "caption": "B) WT, LGP2  KO, HEK293  cells were stimulated with 200 ng/ml of short poly I:C. The expression of SP100, PML, and ANKRD1  mRNA was determined by  RT-qPCR  and normalized to GAPDH  (n = 3, two-way ANOVA, *p <0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "ANKRD1: 27063
LGP2: 79132
GAPDH: 2597
PML: 5371
SP100: 6672"
  },
  {
    "caption": "C, WT and Riplet  KO A549  (C) cells were stimulated with 200 ng/ml of short poly I:C. The expression of SP100  was determined by RT-qPCR (n = 3, two-way ANOVA, *p < 005). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "Riplet: 84282
SP100: 6672"
  },
  {
    "caption": "D) WT and Riplet  KO MEF  (D) cells were stimulated with 200 ng/ml of short poly I:C. The expression of SP100  was determined by RT-qPCR (n = 3, two-way ANOVA, *p < 005). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "Riplet: 71956
SP100: 20684"
  },
  {
    "caption": "E) WT and Riplet  KO BMM  were infected with influenza A virus (Flu) at MOI = 10. PML  and SP100  mRNA expression was determined by  RT-qPCR (n = 3, two-way ANOVA, *p < 0.05). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "PML: 5371
Riplet: 84282
SP100: 6672"
  },
  {
    "caption": "F) WT and Riplet  KO A549  cells were infected with  influenza A virus infection at MOI = 10. WCE was prepared at the indicated time points  and subjected to SDS-PAGE. Proteins were detected by  western blotting  with the indicated antibody.",
    "ncbi_link": "Riplet: 84282"
  },
  {
    "caption": "G, LGP2  or LGP2-4KR stably expressing WT or Riplet  KO HEK293  cells were infected with SeV  (G) IFN-β mRNA levels at indicated  time points were determined by  RT-qPCR. (n = 3, two-way ANOVA, *p < 0.05, ns: not significant (p > 0.05)). Right graph in panel G is an enlargement of Y-axis of the left graph (dotted line). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
IFN-β: 3456
Riplet: 84282"
  },
  {
    "caption": "H) LGP2  or LGP2-4KR stably expressing WT or Riplet  KO HEK293  cells were stimulated with 200 ng/ml of short poly I:C (H).  IFN-β mRNA levels at indicated time points were determined by  RT-qPCR. (n = 3, two-way ANOVA, *p < 0.05, ns: not significant (p > 0.05)). Data information: All data are representative at least two independent experiments, and \"n\" represents the number of samples (biological replicates). Error bars represent standard deviation from the mean.",
    "ncbi_link": "LGP2: 79132
IFN-β: 3456
Riplet: 84282"
  },
  {
    "caption": "(D) Western blot of whole zebrafish larvae, Smyhc1 stained with the F59 antibody. smyhc1+/+ larvae express Smyhc1 at 24hpf, but not at 48hpf. smyhc1-/- larvae do not express Smyhc1.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(E) Smyhc1 immunohistochemistry stain of 24 hpf (hour post fertilization) zebrafish larvae. Filamentous actin is stained with phalloidin (red). Nuclei are stained with DAPI (blue). Smyhc1 is stained with the F59 antibody (green) (Elworthy et al, 2008). smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae display Smyhc1 in the muscle fibers at 24hpf. smyhc1-/- larvae at 24 do not stain positively for Smyhc1. Scale bar represents 50 µm.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(A) Morphologies of smyhc1+/+, smyhc1-/+ and smyhc1-/- embryos are grossly normal at 2 days post fertilization (dpf), despite complete paralysis of smyhc1-/- embryos. In contrast, the smyhc1R673H/+ embryos have notochord kinks in larval stages (arrow head), while smyhc1R673H/R673H embryos have much more severe notochord kinks that compress and distort the body axis (arrow heads). The smyhc1R673H/- embryos completely phenocopy smyhc1R673H/R673H embryos. (B) Quantification of smyhc1R673H embryonic phenotypes at 2 dpf. ",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(B) The predicted mendelian (1:2:1) and experimental ratio of genotypes of progeny from smyhc1R673H/+ in-crosses demonstrates survival at the indicated ages. This ratio quickly skewed toward an overrepresentation of smyhc1+/+ fish with no representation of smyhc1R673H/R673H after 5 dpf. There is also dropout of smyhc1+/R673H fish into adulthood. Number of fish counted per group is indicated.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(A) Gross morphology of smyhc1 mutant adults. Most smyhc1-/- adult fish display dorsal tail curvature, while smyhc1R673H/+ adults have a shortened body axis and variable spinal curves.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(B) Alizarin red staining of bone shows spinal curvature but no bony fusions in the skeleton of smyhc1-/- adults, in contrast to the compression and fusion of vertebrae seen in smyhc1R673H/+ adults. Distal tail regions are highlighted and enlarged.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(A) Time course of light-triggered larval movements were manually counted at indicated times between 24 and 48 hpf. The smyhc1-/- larvae (n = 36) were paralyzed up to 48 hpf. smyhc1R673H/+ mutants (n = 15) twitched slightly less than their smyhc1+/+ siblings (n = 21) at 34hpf. The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(B) Distance travelled during 5 minutes of spontaneous swimming at 6 dpf quantified by motion tracking software (Noldus Ethovision). At 6 dpf, both smyhc1-/- (n = 24) and smyhc1R673H/+ (n = 11) larvae travelled significantly less than smyhc1+/+ larvae (n = 13). The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range.",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(D) Time spent swimming in swim tunnel before fatigue in adults at 6 months post fertilization (mpf). smyhc1+/+ (n = 6), smyhc1-/- (n = 5), smyhc1R673H/+ (n = 5).",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(E) Myoseptal intervals of slow skeletal muscle at 1 dpf in smyhc1+/+ (n = 54), smyhc1-/- (n = 31), smyhc1R673H/+ (n = 45), and smyhc1R673H/R673H (n = 49). Distance between myosepta was measured perpendicular to rostral-caudal body axis at defined mid-body regions in phalloidin stained slow skeletal muscle fluorescence images. The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range. (F) Myoseptal intervals of slow skeletal muscle at 3 dpf in smyhc1+/+ (n = 51), smyhc1-/- (n = 32), smyhc1R673H/+ (n = 64), and smyhc1R673H/R673H (n = 38). The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range. ",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(G) Z-disc intervals (sarcomere length) of slow skeletal muscle at 1 dpf in smyhc1+/+ (n = 380), smyhc1R673H/+ (n = 293), and smyhc1R673H/R673H (n = 268). Distance between z-discs was measured in anti-α-actinin stained slow skeletal muscle fluorescence images. The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range. (H) Z-disc intervals (sarcomere length) of slow skeletal muscle at 3 dpf in smyhc1+/+ (n = 249), smyhc1-/- (n = 278), smyhc1R673H/+ (n = 246), and smyhc1R673H/R673H (n = 252). The central bands of the boxplots represent the median, the boxes of the boxplots represent the interquartile range (between the first and third quartile), and the whiskers represent the minimum and maximum values, up to 1.5 times the interquartile range. Outliers displayed are outside of this range. ",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "(A) Representative morphologies of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 2 dpf after 24 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. All para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis. (B) Representative images of smyhc1+/+, smyhc1R673H/+, and smyhc1R673H/R673H larvae at 3dpf after 48 hour treatment with 0.25% DMSO (control) or 25 μM para-aminoblebbistatin. All larvae treated with para-aminoblebbistatin develop a slight dorsal tail curve and pericardial edema regardless of genotype. Para-aminoblebbistatin-treated smyhc1R673H/+ (n=9) and smyhc1R673H/R673H (n=3) larvae are indistinguishable from smyhc1+/+ unlike the untreated larvae which have markedly curved or distorted body axis. ",
    "ncbi_link": "smyhc1: 321552"
  },
  {
    "caption": "A. In response to a 1 s light pulse, cac alleles lack on transients at day 3 and day 33.",
    "ncbi_link": "cac: 32158"
  },
  {
    "caption": "H. The level of p62 is increased in cacJ brain. I. Quantification of H. Data are presented as means ± SEM. (*: p < 0.05).",
    "ncbi_link": "cac: 32158"
  },
  {
    "caption": "Autophagy defects observed in cac mutants are not due to defects in neurotransmitter release, but due to defects in lysosomal fusion.TEM sections of 1-day-old and 30-days-old photoreceptor terminals of flies raised in 12 h light/dark conditions. A, B, D, and E. stj and Vha100-1 (V0) mutant terminals accumulate AVs upon aging. G, H. n-Syb mutant photoreceptor terminals show increased SVs, but not a significant accumulation of AVs and fusion-primed AVs. J, K, M and N. Vamp7 and fab1 mutant photoreceptor terminals show the highest increase in AV accumulation. C, F, I, L, O. Quantification of the different AVs for each genotype (**: p < 0.01). Eyes from three animals for each genotype at each age were analyzed and the counted cartridge number were listed as \"n = \" in the figure. Data are presented as means ± standard deviation (SD). Scale bars, 1 μm.",
    "ncbi_link": "cac: 32158
fab1: 37033
n-Syb: 38196
stj: 36526
Vamp7: 36015
Vha100–1: 43442"
  },
  {
    "caption": "A. Calbindin and hematoxylin staining of mice cerebella indicates that Cacna1atg-la mice have progressive PC and granule cell loss upon aging. Scale bar, 200 μm.",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": ". B, D. Calbindin (green) and 4',6-diamidino-2-phenylindole (DAPI)(blue) staining of micecerebellum indicates that there are swollen PC axons (arrows) in the granular layers of the Cacna1atg-lamicecerebellum at day 25 (B) and the Cacna2d2du-2Jmice at day 50 (D). Scale bar, 20 μm",
    "ncbi_link": "Cacna1a: 12286
Cacna2d2: 56808"
  },
  {
    "caption": "C, E. The TEM of the axons at the granular layers of the cerebellum showing that many PC axons in Cacna1atg-la and Cacna2d2du-2J mice are swollen and accumulated with numerous mitochondria, autophagosome/MVBs-like structures (red arrows), and various cytoplasmic vesicles or aberrant membrane structures, including stacks of cisternal membranes (blue arrows), and folded ER (yellow arrows). Scale bars for right two panels are 2 μm. Other scale bars are 500 nm",
    "ncbi_link": "Cacna1a: 12286
Cacna2d2: 56808"
  },
  {
    "caption": "F, G. LC3II and p62 are slightly increased in 15-days-old Cacna1atg-la mice and 50-days-old Cacna2d2du-2J mice. b, d are quantification of a and c. Data are presented as means ± SEM. (*: p < 0.05).",
    "ncbi_link": "Cacna1a: 12286
Cacna2d2: 56808"
  },
  {
    "caption": "A. CACNA1A co-localizes with LAMP1 in primary cerebellar cultures of both CTL and Cacna1atg-la mutants. Scale bars, 20 μm.",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": "B. CACNA1A is present as punctae on the Vacuolin-1 enlarged LAMP1 positive lysosomes in primary cerebellar cultures of both CTL and Cacna1atg-la mutants. Scale bars, 20 μm.",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": "A. LysoTracker Red staining of the primary cerebella neurons from Cacna1atg-la mice and WT controls. The control cells show big bright punctae, while the mutant cells have much dimmer and smaller punctae. B, C and D. Quantification of LysoTracker relative intensity (\"n\" represents the counted cell number), LysoTracker positive punctae number and size per cell (\"n\" represents the counted image number)",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": ". E. Lysosomal marker LAMP1 co-localizes with autophagosome marker LC3 in CTL but not Cacna1atg-la mutant cells. Scale bar, 20 μm. F. Quantification of LC3 and LAMP1 co-localization. Data are presented as means ± SD. (ns: not significant; ***: p < 0.001).",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": "A. DQ-BSA labeled late endosomes fuse with LAMP1 labeled lysosomes in CTL but not the mutant cells. Scale bar, 20 μm. B. Quantification of DQ-BSA and LAMP1 co-localization in CTL and Cacna1atg-la cells. Data are presented as means ± SD. (ns: not significant; ***: p < 0.001) C. Bepridil but not ω-agatoxin TK (ω-Aga TK) treatment reduces lysosomal fusion in cultured cerebellar cells. DQ-BSA (Green) labeled late endosomes co-localize with LAMP1 (Red) labeled lysosomes with/without ω-Aga TK (1 µM) or Bepridil (10 µM) treatment. Scale bar, 20 μm. D. Quantification of DQ-BSA and LAMP1 co-localization with ω-Aga TK or Bepridil treatment. Data are presented as means ± SD. (ns: not significant; **: p < 0.001).",
    "ncbi_link": "Cacna1a: 12286"
  },
  {
    "caption": "A, B Temporal expression of Snail genes in the intestinal tract in (A) embryonic E12.5 to E18.5 and (B) postnatal P0 to P20 measured by qRT-PCR. Shown are means ± SD.",
    "ncbi_link": "Snail: 20613"
  },
  {
    "caption": "C, E, G, I Immunohistochemical staining for Snai1/2 (Abcam ab85931) (C) E14.5midgut, (E) E14.5hind gut, (G) postnatal day 14 SI, (I) postnatal day 14 colon. Snai1immunohistochemistry peptide competition controls are shown as inserts (C', E', G', I'). Scale bars: 20 mm.D, F, H, J, K X‐gal staining for β‐galactosidase activity in tissue from Snai2LacZ mice stained in whole mount, sectioned and counterstained with nuclear fast red (D) E14.5midgut, (F) E14.5hind gut, (H) postnatal day 14 SI, (J) postnatal day 14 colon, (K) adult SI. Controls for X‐gal staining are shown as inserts (D', F', H', J').L, M, N Double immunostaining of small intestinalcrypts for Snai1/2 (red) and (M) Lgr5‐GFP (green); (N) merge shows Snai1 is present in both CBCstem cells and proliferating transit amplifying cells. Scale bars: 10 mm.O, P Immunohistochemistry for Snai1 using a different primary antibody (Genetex GTX125918) shows minimal expression of Snai1 in villi. (P) Expression of Snai1 is detected at the base of crypts (P) with strong nuclear expression in CBCstem cells indicated by arrows. Scale bars: 20 mm (O), 10 mm (P).Q Schematic diagram showing Snai1 expression (red) within different cell types in the crypt. SI = small intestine. See also Supplementary Fig S1.",
    "ncbi_link": "Snai2: 20583"
  },
  {
    "caption": "Periodic Acid Schiff (PAS) staining was used to detect goblet cells in sections of small intestine from control and Snai1 KO mice. Graph shows number of goblet cells per crypt-villus axes (n = 3).Immunohistochemistry for synaptophysin was used to detect enteroendocrine cells (marked by arrows). Quantification of enteroendocrine cells per crypt-villus axes in control and Snai1 KO tissue revealed a significant increase in the number of enteroendocrine cells following Snai1 loss (n = 3, P = 0.004).Immunohistochemistry for lysozyme was used to detect Paneth cells. Quantification of Paneth cells in control and Snai1 KO indicates a significant increase in Paneth cell numbers following knockout of Snai1 (n = 4, P = 0.002).",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "Measurement of villus length (μm) (n = 3, P = 0.013) and quantification of enterocytes per crypt-villus unit demonstrate a significant reduction in absorptive enterocytes following Snai1 loss (n = 3, P = 0.036).Measurement of villus length (μm) (n = 3, P = 0.003) 8 days after β‐NF induction demonstrates a significant shortening of villi. Bars represent mean ± SD. Two‐tailed Student's t‐test was used to assess significance. Scale bars: 20 μm.",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "Sections from control and Snai1 KO small intestine were stained for PCNA to detect proliferating cells (arrows depicting proliferating CBC stem cells at the base of crypts). Quantification of total PCNA‐positive cells per crypt and PCNA‐positive cells in the base of crypts both revealed a significant reduction in the number of proliferating cells after conditional depletion of Snai1 (n = 4, P = 0.049, 0.026). Scale bars: 20 μm.",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "The expression of 2 CBCstem cell markers Olfm4 and Lgr5 were examined by in situ hybridisation in control and Snai1KO small intestine. Lgr5 and Olfm4in situ hybridisation staining shows a loss of CBCstem cell marker expression after loss of Snai1 (high magnification inserts depict a representative crypt demarcated by a dotted line). Loss of Snai1 was confirmed in knockout tissue using immunohistochemistry. Scale bars: 20 μm.",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "The analysis of sorted and EGFP‐positive cells from Lgr5‐EGFP‐IRES‐creERT2AhCreSnai1fl/fl and Lgr5‐EGFP‐IRES‐creERT2AhCreSnai1+/+mice 5 days after βNF induction show an ˜tenfold reduction in Lgr5GFP‐positive CBCstem cells.",
    "ncbi_link": "AhCre: 
creERT2: 
IRES: 
Snai1: 20613"
  },
  {
    "caption": "Immunohistochemistry for active caspase‐3 to detect apoptotic cells revealed a significant increase in the number of apoptotic cells in both crypt (n = 5, P = 0.0001) and villus (n = 5, P = 0.005) regions in Snai1KO tissue (arrows mark active caspase‐3‐positive cells). Scale bars: 20 μm.",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "A lineage tracing strategy was employed to determine the fate of CBCcells that lack Snai1. Tissue from Lgr5‐EGFP‐IRES‐creERT2Snai1+/+ (control) and Lgr5‐EGFP‐IRES‐creERT2Snai1fl/fl (Snai1KO) that also contained the ROSA26LacZCre reporter allele was stained with X‐Gal 5 days after tamoxifen injection. Quantification of X‐Gal‐positive foci per cm shows Snai1 knockout tissue failed to lineage trace indicating that no progeny are produced from Snai1 knockout cells. Bars represent mean ± SD (n = 3, P = 0.0001). Scale bars: 0.50 mm. Two‐tailed Student's t‐test was used to assess significance. See also Supplementary Figure S2.",
    "ncbi_link": "Cre: 
creERT2: 
IRES: 
ROSA26LacZ: 
Snai1: 20613"
  },
  {
    "caption": "VillinCreERT2Snai1fl/florganoids treated with tamoxifen show arrested growth after 2 and 4 days of treatment compared to controls. Scale bars: 50 μm.Quantification of viable cell growth in VillinCreERT2Snai1fl/florganoids treated with tamoxifen compared to controls over 4 days. Bars represent mean ± SD. n = 3 experiments per group, **P = 0.002.",
    "ncbi_link": "Cre: 
ERT2: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "Assessment of apoptosis in control and VillinCreERT2 Snai1fl/fl organoids after 4 days of growth. Photographs show an overlay of bright‐field and fluorescent images with propidium iodide and Hoechst staining. Quantification of apoptotic organoids. Bars represent mean ± SD. n = 3 experiments per group, **P = 0.00001. Two‐tailed Student's t‐test was used to assess significance. Scale bars: 50 μm. See also Supplementary Figure S3.",
    "ncbi_link": "Cre: 
ERT2: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "The consequences of Snai1 knockout were analysed over a time course. Immunohistochemistry for Snai1 revealed significant loss of expression at day 5 following induction compared to control. The epithelium is re‐populated by wild‐type cells as shown on day 60. Scale bars: 20 μm.",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "B Immunohistochemistry for synaptophysin was used to detect enteroendocrine cells. Quantification of the number of enteroendocrine cells per crypt-villus axes revealed a significant decrease in enteroendocrine cell numbers when Snai1 levels are elevated (n = 4, P = 0.003).",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "C Immunohistochemistry for lysozyme was used to detect Paneth cells. Quantification of Paneth cell numbers indicated a significant decrease in Paneth cells in the base of crypts in mice with elevated Snai1 levels (n = 5, P = 0.027).",
    "ncbi_link": "Snai1: 20613"
  },
  {
    "caption": "D, E Quantification of total PCNA‐positive cells per crypt revealed a significant increase when Snai1 levels were elevated (n = 4, P = 0.009). This was confirmed in VillinCreERT2 ROSA26Snai1 mice 5 days after induction with tamoxifen where analysis of (E) PCNA‐positive cells in the base of crypts revealed a significant increase in proliferating cells in crypts with elevated Snai1 levels compared to control tissue (n = 4, P = 0.0005). Bars represent mean ± SD.",
    "ncbi_link": "Cre: 
ERT2: 
ROSA26: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "D, E Quantification of total PCNA‐positive cells per crypt revealed a significant increase when Snai1 levels were elevated (n = 4, P = 0.009). This was confirmed in VillinCreERT2 ROSA26Snai1 mice 5 days after induction with tamoxifen where analysis of (E) PCNA‐positive cells in the base of crypts revealed a significant increase in proliferating cells in crypts with elevated Snai1 levels compared to control tissue (n = 4, P = 0.0005). Bars represent mean ± SD.",
    "ncbi_link": "Cre: 
ERT2: 
ROSA26: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "F PCNAimmunostaining (green) and DAPIstaining (blue) of VillinCreERT2ROSA26Snai1 compared to control VillinCreERT2 littermates. An expansion of proliferating CBCcells (indicated by arrows) is observed at the base of crypts. Scale bars: 10 μm.",
    "ncbi_link": "Cre: 
ERT2: 
ROSA26: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "G qRT-PCR analysis of stem cell marker expression in the small intestine from VillinCreERT2 ROSA26Snai1 compared to control VillinCreER2T littermates. Bars represent mean ± SD. n = 3 experiments per group, Olfm4 P = 0.013, Cdh1/E‐cadherin P = 0.003, Lgr5 P = 0.013.",
    "ncbi_link": "Cre: 
ERT2: 
ROSA26: 
Villin: 
Cdh1: 12550
E‐cadherin: 12550
Lgr5: 14160
Olfm4: 380924
Snai1: 20613"
  },
  {
    "caption": "H CD44v6 immunostaining of tissue from AhCre control compared to AhCre RosaSnai1 tissue. A significant increase in CD44v6‐positive cells localised at the base of crypts (depicted by arrows) was observed. Bars represent mean ± SD. n = 3 mice per group, *P = 0.00023. Two‐tailed Student's t‐test was used to assess significance. Scale bars: 10 μm.",
    "ncbi_link": "AhCre: 
Rosa: 
Snai1: 20613"
  },
  {
    "caption": "VillinCreERT2 RosaSnai1 organoids treated with tamoxifen show slower growth after 2 and 4 days of treatment compared to controls. Scale bars: 50 μm.Quantification of viable cells in VillinCreERT RosaSnai1 organoids treated with tamoxifen compared to control growth over 4 days. Bars represent mean ± SD. n = 3 experiments per group, **P = 0.002.",
    "ncbi_link": "Cre: 
ERT2: 
Rosa: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "Assessment of apoptosis in control and VillinCreERT2 RosaSnai1 organoids after 4 days of growth. Photographs show an overlay of bright‐field, propidium iodide and Hoechst fluorescence. Scale bars: 50 μm.Quantification of apoptotic organoids with and without Wnt3A treatment shown as mean ± SD. n = 3 experiments per group, **P = 0.00003. Two‐tailed Student's t‐test was used to assess significance.",
    "ncbi_link": "Cre: 
ERT2: 
Rosa: 
Villin: 
Snai1: 20613"
  },
  {
    "caption": "A-C Droplet digital PCR analysis of Bmf, Bbc3/Puma and Bcl2l 11/Bim after conditional Snai1 loss in in vitro organoid culture. VillinCreERT2 Snai1+/+ (control) and VillinCreERT2 Snai1fl/fl SI organoids were treated for 24 h with tamoxifen. No differences in gene expression were observed (n = 3).",
    "ncbi_link": "Cre: 
ERT2: 
Villin: 
Bbc3: 170770
Puma: 170770
Bcl2l 11: 12125
Bim: 12125
Bmf: 171543
Snai1: 20613"
  },
  {
    "caption": "D qRT-PCR analysis of Serinc3 downregulation after conditional Snai1 loss in in vitro organoid culture. VillinCreERT2 Snai1+/+ (control) and VillinCreERT2 Snai1fl/fl SI organoids were treated for 24 (P = 0.0001) and 72 h (P = 0.006) with tamoxifen. Bars represent mean ± SD. n = 3 mice per group.",
    "ncbi_link": "Cre: 
ERT2: 
Villin: 
Serinc3: 26943
Snai1: 20613"
  },
  {
    "caption": "E SW480 cells, which transiently express GFP‐SNAI1, were used to detect direct binding of SNAI1 to the promoters of known target genes CDH1, IL8 and a novel target SERINC3 revealed by microarray analysis. An unrelated DNA region was used as a negative control. Anti‐GFP antibody was used to immunoprecipitate GFP‐tagged SNAI1, while IgG control antibody was used as a negative control. The results are given as relative enrichment compared to input material and are representative of three independent experiments.",
    "ncbi_link": "CDH1: 999
IL8: 3576
SERINC3: 10955
SNAI1: 6615"
  },
  {
    "caption": "G. RT-qPCR data for select ZGA genes activated following MERVL::tdTomato expression in mouse 2-cell embryos derived from ICSI or SCNT. Results were normalized based on the geometric mean of the expression levels of two reference genes (Ywhaz and Gapdh). Error bars, s.e.m., n = 3. ***P < 0.001 by two-tailed Student"s\u2028 t",
    "ncbi_link": "Gapdh: 
Ywhaz: "
  },
  {
    "caption": "I. RT-qPCR analysis for somatic cell genes in SCNT 1-cell embryos, 2-cell tdTomato+, and 2-cell tdTomato- embryos. Results were normalized based on the geometric mean of the expression levels of two reference genes (Ywhaz and Gapdh). Error bars, s.e.m., n = 3. ***P < 0.001 by two-tailed Student"s\u2028 t",
    "ncbi_link": "Gapdh: 
Ywhaz: "
  },
  {
    "caption": "A, B RT-qPCR analysis of KDM6A (A) and KDM6B (B) mRNA levels in SCNT 2-cell embryo. Data shown are mean expression values relative to Gapdh. The value in ICSI control was set as 1. Error bars, s.e.m., n ≥ 3. **P < 0.01 by Student"s t",
    "ncbi_link": "KDM6A: 22289
KDM6B: 216850"
  },
  {
    "caption": "C. The sketch of KDM6A and KDM6B in vitro transcription vector (right), and the integrity of in vitro transcripted mRNA was confirmed by electrophoresis with formaldehyde gels (left). M, marker; T7, in vitro transcription promoter; HA, hemagglutinin epitope tag",
    "ncbi_link": "KDM6A: 22289
KDM6B: 216850"
  },
  {
    "caption": "G. The bar chart showing the efficiency of blastocyst formation. Injection of KDM6A mRNA improved the preimplantation development rate of SCNT embryos. Error bars, s.e.m., n ≥ 3. **P < 0.01, ***P < 0.001 by two-tailed Student"s\u2028 t-test. n.s., not signif",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "K. Preimplantation development rates in the KDM6A-HA, KDM6B-HA, or KDM6A-cM/-nM/-ncM-HA mRNA-injected and non-injected control SCNT groups. The efficiency was calculated based on the number of cleavage embryo. Error bars, s.d., the total numbers of cleavage embryos in each condition (KDM6A-HA, KDM6B-HA, KDM6A-cM/-nM/-ncM-HA, and Control) from three independent experiments were 275, 199, 290, 221, 244, and 286, respectively.",
    "ncbi_link": "KDM6A: 22289
KDM6B: 216850"
  },
  {
    "caption": "A. RT-qPCR analysis of KDM6A/B in SCNT embryos injected with siRNA-6A or siRNA-6B. The SCNT embryos were subject to injection of 10 μM or 20 μM\u2028 siRNA as indicated. Data are mean expression relative to Gapdh with siRNA-control normalized to 1. Error bars, s.e.m., n = 3. **P < 0.01, ***P < 0.001 according to two-tailed Student"s t-test. n.s., not significant. B. The bar chart shows the KDM6A/B transcript levels in SCNT embryo with 20 μM siRNA-6A/B. All data are mean expression relative to Gapdh with control siRNA injected SCNT embryos normalized to 1.\u2028 Error bars, s.e.m., n = 3, **P < 0.01 by Student&quo",
    "ncbi_link": "Gapdh: 
6A: 22289
KDM6A: 22289
6B: 216850"
  },
  {
    "caption": "C. Immunofluorescence staining results showing H3K27me3 of 2-stage SCNT embryos. Embryo was injected with siRNA as indicated. The H3K27me3 levels between control and double injected with siRNA-6A-6B cannot observe any difference, but a marked decrease was observed when injected with either siRNA-6A or siRNA-6B. Scale bar, 20 μm",
    "ncbi_link": "6A: 22289
6B: 216850"
  },
  {
    "caption": "F. Representative images of SCNT embryos at 115 h after injection of different siRNA as indicated. These images are representative examples of the quantification shown in Fig 5G. n ≥ 3. Scale bar, 50 μm. G. Injection of siRNA-6B improved the preimplantation development rate of SCNT embryos. Both cumulus cells, Sertoli cells, and C57 MEF cells were used as donor cells. The bovine intraspecies SCNT embryos derived from bovine ear fibroblast cells. Shown is the percentage of embryos that reached the indicated stages. ♂ and ♀ indicated the male and female, respectively. Error bars, s.d., n ≥ 3. H ",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "RT-qPCR analysis for select ZGA genes in ICSI and SCNT embryos. The SCNT embryo was injected with siRNA as indicated. Results were normalized based on the geometric mean of the expression levels of two reference genes (Ywhaz and Gapdh). Error bars, s.e.m., n = 3. *P < 0.05, **P < 0.01, ***P < 0.001 according to two-tailed Student"s t-test. n.s., not signif",
    "ncbi_link": "Gapdh: 
Ywhaz: "
  },
  {
    "caption": "B. Representative fluorescence images of siRNA-control or siRNA-6B injected SCNT embryos. Scale bar, 50 μm",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "C. Quantification of embryos that expression tdTomato after injection with siRNA-control or siRNA-6B. Numbers of observed embryos are indicated. n ≥ 3, Error bars, s.e.m., ***P < 0.001 according to two-tailed Student"s t",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "D. Representative images of green fluorescence in Oct4::EGFP reconstructed blastocysts derived from injected siRNA-control or siRNA-6B SCNT embryos. Representative images from ≥ 25 embryos analyzed in three independent micromanipulations are shown. Green fluorescence indicates that the Oct4::EGFP transgene has been expressed. Scale bar, 50 μm",
    "ncbi_link": "6B: 216850
Oct4: 18999"
  },
  {
    "caption": "E. Oct4::EGFP was up-regulated significantly in ICSI embryos compared with SCNT embryos at blastocyst stages, as determined by RT-qPCR. Data shown are mean expression values relative to Gapdh. The value in ICSI embryos was set as 1. Error bars, s.e.m., n ≥ 3. *P < 0.05, ***P < 0.001 by two-tailed Student"s\u2028 t",
    "ncbi_link": "EGFP: 
Gapdh: 
Oct4: 18999"
  },
  {
    "caption": "F. Representative image of cloned mice derived by siRNA-6B injected SCNT embryos",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "G. Bar graph showing the efficiency of attachment to the feeder cells (left) and si6B-mdx-ntES derivation (right). The mdx sick mice tail-tip fibroblasts as nuclear donors. N, total number of embryos analyzed for each condition. Results are from four replicate experiments",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "H. Immunostaining images of si6B-mdx-ntES expressed pluripotency markers. Scale bar, 50 μm",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "I. The si6B-mdx-ntES possessed multiple-differentiation potential, as shown in embryoid body.\u2028 Scale bar, 100 μm.",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "J. An image of a chimeric mouse derived from si6B-mdx-ntES",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "B. Heatmap comparing ZGA genes expression between WT-2 and NT-2 and si6B-NT embryos (FC > 5, FPKM > 5 in each replicate; left). A total of 1,813 DEGs are classified into two groups by unsupervised hierarchical clustering. KEGG and GO analysis of the two groups by unsupervised hierarchical clustering (right).",
    "ncbi_link": "6B: 216850"
  },
  {
    "caption": "E. Venn diagram showing the overlap between the genes that failed to be activated in SCNT 2-cell embryos and derepressed in knock-down KDM6B (left). Heat-map, KEGG and GO enrichment showing the expression pattern of 319 overlap genes (FC > 5, FPKM >5; right).",
    "ncbi_link": "KDM6B: 216850"
  },
  {
    "caption": "G. Representative localization of Xist expression in the nuclei of SCNT embryos injected with siRNA-6A, siRNA-6B or siRNA-Xist (left). Arrows indicate the blastomeres enlarged in the bottom panels. The ratios of blastomeres classified according to the positive or negative expression of Xist analyzed by RNA-FISH (right). Each bar represents a single embryo.",
    "ncbi_link": "6A: 22289
6B: 216850
Xist: 213742"
  },
  {
    "caption": "H. Large-scale qPCR analysis of Xist and eight X-linked genes in 4-cell stage male embryo. Each rectangle bar represents the expression value detected by single embryo RT-qPCR. The number of embryos in each group is indicated. Coloured bars indicate expression levels.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "I. Image of full-term cloned pups derived from NT Sertoli cells injected with siRNA-control, siRNA-Xist, or siRNA-Xist-6B.",
    "ncbi_link": "6B: 216850
Xist: 213742"
  },
  {
    "caption": "RT-PCR analysis of SPPL2c expression in different murine tissues. Total RNA from the indicated tissues was either transcribed into cDNA prior to PCR amplification (+RT) or, as negative control, used directly as template (-RT). A fragment of the actin ORF was amplified as control.",
    "ncbi_link": "actin: 
SPPL2c: 237958"
  },
  {
    "caption": "Western Blot analysis of total lysates from testis isolated from wild type or SPPL2c-/- using antibodies against C- (D) or N-terminal (E) epitopes of SPPL2c. Lysates from HeLa cells transiently expressing the SPPL2c isoforms were analysed in parallel.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "SPPL2c was visualised by indirect immunofluorescence in HeLa cells transiently expressing C-terminally Myc-tagged murine SPPL2c isoform A. For detection of SPPL2c, either anti-Myc or the SPPL2c antiserum (C-terminal epitope) were employed as indicated together with anti-KDEL, anti-GM130 or anti-ERGIC53 as indicated in order to label the ER, the cis Golgi apparatus or the ER-Golgi intermediate compartment (ERGIC), respectively.",
    "ncbi_link": "Myc: 
SPPL2c: 237958"
  },
  {
    "caption": "Lysates from HEK293 cells transiently transfected with murine SPPL2c-myc (isoform A) were treated with the glycosidases PNGase F or Endo H as indicated prior to Western blot analysis with anti-SPPL2c (C-term). Deglycosylation of endogenously expressed LIMP2 was analysed as control.",
    "ncbi_link": "myc: 
SPPL2c: 237958"
  },
  {
    "caption": "N-glycosylation of endogenous SPPL2c is similar to the overexpressed protein. Total lysates from testis of wild type or SPPL2c-/- mice were treated",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "HEK293 cells were transiently transfected with murine N-terminally HA-tagged heme oxygenase 1 (HA-mHO-1) alone or in combination with active or inactive (D/A) murine SPP or SPPL2c. Substrate levels were determined by Western blot analysis with anti-HA. For detection of SPP, an antiserum recognizing both endogenous human (h) and overexpressed murine (m) SPP was employed. Murine SPPL2c was visualised using the antiserum generated against the C-terminus of the protein. Actin was detected to control for equal protein loading.",
    "ncbi_link": "HA: 
heme oxygenase 1: 15368
mHO-1: 15368
SPP: 237958
SPPL2c: 237958"
  },
  {
    "caption": "Immunofluorescence analysis of HeLa cells transiently expressing murine HO-1 (HA-mHO-1) alone or together with active or inactive (D/A) SPPL2c-myc. Substrate and proteases were visualised using the HA and Myc epitopes, respectively.",
    "ncbi_link": "HA: 
myc: 
HO-1: 15368
mHO-1: 15368
SPPL2c: 237958"
  },
  {
    "caption": "The TA protein Ube2J1 is not proteolysed by co-expressed SPP or SPPL2c in HEK293 cells. Western blot analysis was performed",
    "ncbi_link": "SPP: 237958
SPPL2c: 237958"
  },
  {
    "caption": "Differential cleavage of CYB5a, RAMP4-2 and RAMP4 by SPPL2c and SPP. Substrates and proteases were co-expressed in HEK293 cells followed by Western blot analysis as described above. Densitometric quantification from at least n=3 independent experiments was performed. Substrate levels were normalised and compared to cells without protease-overexpression.",
    "ncbi_link": "CYB5a: 109672
RAMP4: 28146
RAMP4-2: 72661
SPP: 237958
SPPL2c: 237958"
  },
  {
    "caption": "HEK293 cells expressing HA-RAMP4-2 alone or in combination with SPPL2c or SPP were treated with 100 µM (Z-LL)2-ketone (ZLL), 5 µM inhibitor X (InX), 5 µM DAPT or DMSO as control. RAMP4-2 band intensity was quantified from blots of three independent experiments and normalised to cells just over-expressing the substrate.",
    "ncbi_link": "HA: 
RAMP4-2: 72661
SPP: 237958
SPPL2c: 237958"
  },
  {
    "caption": "Microsomes isolated from testis of wild type and SPPL2c-/- mice were solubilised in 1% digitonin and proteins were separated by blue native PAGE. After transfer to PVDF membrane, SPPL2c and SPP were detected using the polyclonal antisera introduced above.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Histochemical visualization of β-galactosidase (β-gal) reporter activity revealed SPPL2c expression within seminiferous tubules. Cryo-sections from PFA-fixed wild type and SPPL2c-/- testis were stained with X-Gal as β-gal substrate.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Immunohistochemical detection of SPPL2c was performed on cryosections of Bouin-fixed wild type and SPPL2c-/- testis. The SPPL2c antiserum directed against a C-terminal epitope of the protease and diaminobenzidine as peroxidase substrate were employed. Nuclei were stained with hematoxylin. Scale bar, 100 µm (upper panel) or 50 µm (lower panel).",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "SPPL2c levels were compared in total lysates prepared from testis of wild type mice sacrificed at the age of 4, 6, 8 or 12 weeks by Western blotting. A testis lysate from an adult SPPL2c-/- mouse was used as negative control.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "The weight of both testicles of wild type and SPPL2c-/- mice (n=12 per genotype) was determined and normalised to the body weight.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Paraffin sections from Bouin-fixed wild type and SPPL2c-/- testis were stained with hematoxylin & eosin (H&E). Scale bars, 100 µm.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "In H&E stained paraffin-sections from Bouin-fixed wild type and SPPL2c-/- testis, the mean number of elongated spermatids per seminiferous tubule was determined. Cells were counted in 20 tubuli in sections from n=6 mice per genotype.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "SPPL2c is not present in mature spermatozoa. Western blot analysis of total lysates of wild type (+/+) and SPPL2c-/- testis, epididymis and spermatozoa recovered from the cauda epididymidis/vas deferens for SPPL2c.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Mature sperm were isolated from the epididymis of wild type or SPPL2c-deficient mice and analysed by phase-contrast microscopy. Representative pictures of morphologically normal spermatozoa are depicted. Scale bars, 10 µm.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Reduced motility of SPPL2c-/- sperm cells. Spermatozoa were recovered from the cauda epididymidis of wild type and SPPL2c-/- mice (n=3) and subjected to computer-assisted sperm analysis. Average path velocity (VAP), straight line velocity (VSL) and curvilinear velocity (VCL) were determined in micrometer per second.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Carbonate-washed total membrane fractions from wild type and SPPL2c-/- testis (n=5) were subjected to a label-free quantitative proteome analysis. For each quantified protein, a log2 intensity ratio between SPPL2c-deficient and wild type samples was calculated. Negative values indicate a depletion and positive values an enrichment in SPPL2c-/- samples. In the depicted volcano plot the negative log10 of the p value (y axis) is plotted versus the log2 intensity ratio of SPPL2c-/- versus wild type samples (x axis). All proteins above the significance level of p<0.01 (unpaired Student's t test) are coloured in red. The hyperbolic curve indicates the threshold for a permutation-based FDR correction for multiple hypotheses with p = 0.05 and s0 = 0.1.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "HeLa cells were transiently transfected with N-terminally HA-tagged PLN (HA-PLN) and inactive (D/A) SPPL2c-myc The expressed proteins were visualised by indirect immunofluorescence via their HA and Myc epitopes.",
    "ncbi_link": "HA: 
myc: 
PLN: 18821
SPPL2c: 237958"
  },
  {
    "caption": "HEK293 cells were transiently transfected with HA-PLN alone or in combination with active or inactive (D/A) murine SPPL2c Isoform A (D) or Isoform B (E). Substrate processing was analysed by Western blotting with anti-HA. SPPL2c expression was confirmed with the antiserum against the C-terminal epitope. Actin was detected to confirm equal protein loading.",
    "ncbi_link": "HA: 
PLN: 18821
SPPL2c: 237958"
  },
  {
    "caption": "Subcellular localisation of the PLN mutants was analysed by indirect immunofluorescence using anti-HA in combination with anti-protein disulphide isomerase A6 (PDIA6) to stain the ER. The 37-41A and 47-51 PLN mutants were not expressed in relevant amounts.",
    "ncbi_link": "PLN: 18821"
  },
  {
    "caption": "HEK293 cells were transiently transfected with wild type or mutated HA-PLN alone or together with SPPL2c isoform A.",
    "ncbi_link": "HA: 
PLN: 18821
SPPL2c: 237958"
  },
  {
    "caption": "Quantification of n=5 experiments as shown in (H). For each PLN variant, the residual PLN in SPPL2c co-expressing cells is depicted as % of PLN in absence of the protease.",
    "ncbi_link": "PLN: 18821
SPPL2c: 237958"
  },
  {
    "caption": "Accumulation of endogenous PLN in the testis of SPPL2c-/- mice. PLN was immuno-precipitated (IP) from equal protein amounts of total lysates of wild type or SPPL2c-/- testis with the mouse monoclonal antibody. Western blot analysis of the IPs was performed with the rabbit monoclonal PLN antibody. SPPL2c and actin were detected from total lysates directly.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Expression of PLN in murine testis from wild type (wt) SPPL2c-/- (2c-/-) was quantified by qPCR.",
    "ncbi_link": "PLN: 18821
SPPL2c: 237958"
  },
  {
    "caption": "Immunohistochemical detection of PLN in paraformaldehyde (PFA)-fixed testis from wild type and SPPL2c-/- mice. Cryosections were stained using a rabbit monoclonal PLN antibody or normal rabbit IgG as negative control and diaminobenzidine as peroxidase substrate.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "Intracellular Ca2+ concentrations were analysed in testis suspensions from either wild type or SPPL2c-deficient mice using the Ca2+-sensitive probe Fluo4-AM. Individual germ cell populations were identified Bars indicate Median Fluo4-AM fluorescence ± SD of 8 individual samples from 3 mice per genotype normalised to those of wild type samples.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "B (left) SRM images of paraspeckles in HAP1 NEAT1 ∆3′ mutant cells (∆3′) detected by NEAT1_5′ (green) and  NEAT1_15k (magenta) FISH probes in the presence of MG132 (5 μM for 6 h). Scale bar, 500 nm. (right) Graph showing the proportion of paraspeckles with localization of the NEAT1  3′ ends in the core or in the core and shell (n = 44).",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "B SRM images  of the paraspeckles in ∆0-0.8kb and ∆0-1.9kb (∆5′) cells treated with MG132  (5 μM for 6 h) detected by NEAT1_5′, 1k, and 2k (green) and NEAT1_3′ (magenta) FISH  probes. Scale bar, 500 nm.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "D (left)  EM observation of the paraspeckles in ∆5′ cells treated with MG132 (5 μM for 17 h) using NEAT1_5′ probes. Scale bar, 100 nm. (middle) Graph showing the proportion of localization of NEAT1_5′ probes (347 gold particles) within the paraspeckles in ∆5′ cells. (right) Graph showing the proportion of the localization of NEAT1_5′ probes in each paraspeckle in ∆5′ cells (n = 20). The box plot shows the median (inside line), 25-75 percentiles (box bottom to top), and 10-90 percentiles (whisker bottom to top).",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "B SRM images  of the paraspeckles in MG132-treated (5 μM for 6 h) HAP1 NEAT1  ∆5′/∆3′ cells detected by NEAT1_2k (green) and NEAT1_15k FISH probes (left, magenta) or  NONO immunofluorescence (IF) (right, magenta). Scale bar, 500 nm.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "D (upper)  EM observation of the paraspeckles in MG132-treated (5 μM for 17 h) ∆5′/∆3′ cells using NEAT1_5′ (left) and NEAT1_D2 probes (right). Scale bar, 100 nm. (middle) Graph showing the proportion of the  localization of NEAT1_5′ (left, 310 gold particles) and NEAT1_D2 (right, 294 gold particles) probes within the paraspeckles in HAP1 NEAT1 ∆5′/∆3′ cells. (lower) Graph showing the proportion of the localization of NEAT1_5′ (left, 19 cells) and D2 (right, 22 cells) probes in each paraspeckle in ∆5′/∆3′ cells. Each box plot shows the median (inside line), 25-75 percentiles (box bottom to top), and 10-90 percentiles (whisker bottom to top).",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "B Quantitation of NEAT1_2  by RT-qPCR in WT and ∆5′/∆3′/∆PAS cells with or without MG132 treatment (6 h). Data are represented as mean ± SD (n = 3).",
    "ncbi_link": "NEAT1_2: 283131"
  },
  {
    "caption": "C The paraspeckles  in WT and ∆5′/∆3′/∆PAS cells detected by SRM using NEAT1_5′ and 2k FISH probes (green), and NONO IF (magenta) under the conditions shown in (B). Scale bar, 500 nm.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": " (A) Binding of wild type DUBm-Ubp8 to monoubiquitin. (B) Binding of DUBmUbp8C146A to monoubiquitin. (C) Binding of DUBm-Ubp8C146S to monoubiquitin. (D) Binding of DUBm-Ubp8C146R to monoubiquitin. (E) Binding of DUBm-Ubp8C146A to K48 diubiquitin. (F) Binding of DUBm-Ubp8C146S to K48 diubiquitin. ",
    "ncbi_link": "Ubp8: 855263"
  },
  {
    "caption": "Binding was measured by fluorescence polarization using N-terminally TAMRA-labeled monoubiquitin. The dissociation constants for ubiquitin binding to USP4 WT and C311A are 92 ± 21 nM (Clerici et. al, 2014) and 0.60 ± 0.17 nM, respectively. Error bars are s.d. calculated on five measurements per point.",
    "ncbi_link": "USP4: 7375"
  },
  {
    "caption": " (A) Equilibrium binding of OTUD1 C320A and C320R to K63-linked diubiquitin was measured by fluorescence polarization using FlAsH tagged K63-linked diubiquitin in which the proximal ubiquitin was fluorescently-labeled. Error bars indicate s.d. and are based on three measurements per data point. One representative experiment of two is shown. ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (B) Whole cell lysates of HEK293 cells expressing HA-tagged OTUD1 WT, C320R, and C320A were immunoblotted with indicated antibodies. One representative experiment of three is shown. ",
    "ncbi_link": "HA: 
OTUD1: 220213"
  },
  {
    "caption": " Polyubiquitin chains were co-immunoprecipitated with FLAG-PSMD4, an ubiquitin receptor for the 26S proteasome, from cells expressing either USP14 wild-type, C114A, or C114R. One representative experiment of two is shown. ",
    "ncbi_link": "FLAG: 
PSMD4: 5710
USP14: 9097"
  },
  {
    "caption": "(B) HA-ATG9A-BirA* was expressed in HCT-116 ATG13 WT, ATG13 KO or ATG13 KO cells reconstituted with WT ATG13  or ATG13  ∆HORMA. Cells were grown in full DMEM media, treated with 50 µM  biotin for 12 hrs, followed by detergent lysis and incubation with streptavidin resin. The graph on right shows quantification of normalized ATG101  infrared signal. Mean ± SEM, n=3 (biological replicates). Significance measured using RM one-way ANOVA test followed by Fisher's LSD tests.",
    "ncbi_link": "HA: 
ATG13: 9776
ATG9A: 79065
BirA: 948469"
  },
  {
    "caption": "(C) Cells were treated as in panel B but included reconstitution with  ATG13 ∆2AA mutant. The graph on right shows quantification of normalized ATG101 infrared signal. Mean ± SEM, n=3 (biological replicates). Significance measured using RM one-way ANOVA test followed by Fisher's LSD tests. (right).",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "(D) HA-ATG9A-BirA* was overexpressed in WT and ULK1/2 Double KO MEFs. Cells were subjected to streptavidin pulldown and immunoblotting with indicated antibodies. The graph on right shows quantification of normalized ATG13 infrared signal. Mean ± SEM. n=3 (biological replicates). Significance measured using one-sample t-test compared to hypothetical mean of 1 (right). ns=p>0.05, *=p≤0.05, **= p≤0.01, ***=p≤0.001, ****= p≤0.0001.",
    "ncbi_link": "HA: 
ATG9A: 79065
BirA: 948469
ULK1: 22241"
  },
  {
    "caption": "(A)-(G) Representative images of  ATG9A colocalization with different  organelle  and autophagy markers. HCT-116 ATG9A-HA KI-ATG13 WT or ATG13 KO cells were grown in full DMEM media, fixed and labeled with antibodies for HA and indicated organelle/cellular markers and imaged (Scaler bar=10 µm). (H) Quantification of ATG9A colocalization  with indicated organelle markers of golgi  (GOLGIN97), mitochondria (TUFM), ER (PDIA3), endosomal system (VPS26A),  early endosome (EEA1), lysosome  (LAMP1), autophagy adaptor (p62), and autophagosome markers (ATG16L1, WIPI4, ATG2A, LC3II, WIPI2) respectively. Mean ± SEM, n=1 independent experiment with 30 technical replicates. Images for p62 colocalization (G) are from the same single independent experiment",
    "ncbi_link": "HA: 
ATG13: 9776
ATG9A: 79065"
  },
  {
    "caption": "(A) Endogenous p62/SQSTM1  level in HCT-116 ATG9A-HA KI-ATG13 WT, ATG13  KO, ATG101 KO, ATG9A KO and FIP200 KO clones was measured by  immunoblotting  with indicated antibodies. Cells were grown in full DMEM media, treated with or without 100 nM Bafilomycin  for 24 hrs and whole cell lysates were subjected to  immunoblotting (left). The graph on right shows quantification of normalized p62  infrared signal. Mean ± SEM, n=3 (biological replicates). Significance measured using RM one-way ANOVA test followed by Fisher's LSD tests (right). (B) Endogenous p62/SQSTM1 level in HEK-293T ATG13 WT,  ATG13 KO, ATG101 KO, ATG9A KO and FIP200 KO clones was measured by immunoblotting with indicated proteins. Cells were grown in full DMEM media, treated with or without 100 nM Bafilomycin  for 24 hrs and whole cell lysates were subjected to immunoblotting. Mean ± SEM, n=3 (biological replicates). Significance measured using RM one-way ANOVA test followed by Fisher's LSD tests (right).",
    "ncbi_link": "HA: 
ATG101: 60673
ATG13: 9776
ATG9A: 79065
FIP200: 9821"
  },
  {
    "caption": "(C) Confocal images of ATG9A colocalization with p62/SQSTM1. HCT-116 ATG9-HA KI-ATG13 WT, ATG13  KO, ATG101  KO, ATG9A KO and FIP200 KO cells were grown in full DMEM media, fixed, labeled with antibodies for HA and p62/SQSTM1 and imaged (Scale bar 10 µm). ATG101 KO was stained and quantified separately. Images are from the same single independent experiment (D) Quantification of average surface area of p62/SQSTM1 puncta in C. Mean ± SEM, n=1 independent experiment with 30 technical replicates. ATG101 KO was stained  and quantified separately. Mean ± SEM, n=1 independent experiment with 30 technical replicates. A break was inserted in the Y axis to accommodate the wide range of p62/SQSTM1 puncta sizes. (E) Quantification of ATG9A colocalization with p62/SQSTM1. Mean ± SEM, n=1 independent experiment with 30 technical replicates. ATG101 KO was stained  and quantified separately. Mean ± SEM, n=1 independent experiment with 30 technical replicates.",
    "ncbi_link": "HA: 
ATG101: 60673
ATG13: 9776
ATG9: 79065
ATG9A: 79065
FIP200: 9821"
  },
  {
    "caption": "(A) Endogenous p62/SQSTM1 level was measured in HCT-116 ATG9A-HA KI-ATG13 WT, ATG13 KO OR ATG13 KO cells reconstituted with ATG13 WT, ATG13 ΔHORMA and ATG13  Δ2AA by immunoblotting  with indicated proteins (left). Cells were grown in full DMEM media and whole cell lysates were subjected to  immunoblotting (left). Quantification of normalized p62 infrared signal. Mean ± SEM, n=3 (biological replicates). Significance measured using RM one-way ANOVA test followed by Fisher's LSD tests (right). (B) HCT-116 cells in A were incubated in EBSS for 4 hours then processed and analyzed as in A.",
    "ncbi_link": "HA: 
ATG13: 9776
ATG9A: 79065"
  },
  {
    "caption": "(C) Confocal  images of ATG9A colocalization with  p62/SQSTM1 in HCT-116 ATG9A-HA KI-  ATG13  WT, ATG13 KO or ATG13 KO cells reconstituted with ATG13 WT, ATG13 Δ2AA and ATG13  ΔHORMA. Cells were grown in full DMEM media, fixed, labelled with antibodies for HA and p62/SQSTM1 and imaged (Scale bar=10 µm). Images are from the same single independent experiment (D) Quantification of average surface area of p62/SQSTM1 puncta in C. Mean ± SEM, n=1 independent experiment with 30 technical replicates. A break was inserted in the Y axis to accommodate the wide range of p62/SQSTM1 puncta sizes. (E) Quantification of ATG9A colocalization  with p62/SQSTM1 in C. Mean ± SEM, n=1 independent experiment with 30 technical replicates.",
    "ncbi_link": "HA: 
ATG13: 9776
ATG9A: 79065"
  },
  {
    "caption": "(B) Confocal images of Ubiquitin colocalization with p62/SQSTM1 in HCT116 ATG13 WT and HCT116 ATG13 KO cells. Cells were grown in full DMEM media, fixed, labelled with antibodies for Ubiquitin and p62/SQSTM1 and imaged (Scale bar=10 µm) (left). Quantification of Ubiquitin colocalization  with  p62/SQSTM1 (right). Mean ± SEM, n=1 independent experiment with 30 technical replicates.",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "(C) Modified pulse chase experiment. HEK293T ATG13 WT and  HEK293T ATG13 KO cells stably expressing HA ATG9A-BirA* were pulse labeled with  biotin for 24 hours, media was replaced with full DMEM and streptavidin pulldown was performed at indicated time points. Quantification of normalized  p62  infrared signal. Mean ± SEM, n=3 (biological replicates). Significance measured using Student's t test (bottom). ns=p>0.05, *=p≤0.05, **=p≤0.01, ***=p≤0.001, ****= p≤0.0001.",
    "ncbi_link": "HA: 
ATG13: 9776
ATG9A: 79065
BirA: 948469"
  },
  {
    "caption": "(C) Confocal images of Venus colocalization with  ATG9A  and ULK1 in HCT116 ATG9A-HA KI ATG13-ATG101 double KO cells stably expressing  VenusC-ATG101-3X FLAG and VenusN-ATG13-Myc or VenusN-ATG13 Δ2AA-Myc. Cells were grown in full DMEM media, fixed, labelled with antibodies for HA  and  ULK1 and imaged (Scale bar=10 µm). Quantification of overlap shown as percent of total Venus puncta (bottom). Mean ± SEM, n=1 independent experiment with 10 technical replicates.",
    "ncbi_link": "FLAG: 
HA: 
Myc: 
Venus: 
ATG101: 60673
ATG13: 9776
ATG9A: 79065"
  },
  {
    "caption": "(E) Confocal images of EGFP-p62/SQSTM1 colocalization with HA ATG9A and ATG13  in HCT116 ATG9A-HA KI cells stably expressing EGFP-p62/SQSTM1. Cells were grown in full DMEM media with or without 1 μM Wortmannin for time 4 hrs, fixed, labelled with antibodies for HA  and ATG13 and imaged (Scale bar=10 µm).",
    "ncbi_link": "HA: 
ATG9A: 79065"
  },
  {
    "caption": "(A) Δccc1/pGAL‐H+L cells were transformed with a plasmid containing a methionine regulated CCC1 (pMET3CCC1). Cells were grown in medium with galactose for 20 h, washed and incubated in galactose (•), glucose with 10 × methionine (▵), glucose (○) or glucose without methionine (▾) for 10 h. Cells were then harvested and ferritin levels determined by ELISA. Error bars represent the standard deviation from three different experiments in duplicate. The absence of methionine leads to expression of the vacuolar iron transporter Ccc1p.",
    "ncbi_link": "CCC1: 850917
ccc1: 850917"
  },
  {
    "caption": "(B) erg6‐2 and erg6‐2 pGAL‐H+L strains were grown in medium with galactose and 250 μM FeSO4 for 24 h. Cells were then washed and incubated in galactose or glucose in the absence or presence of 50 μM MG132 for 7 h.",
    "ncbi_link": "erg6‐2: 855003"
  },
  {
    "caption": "(C) Cells were then harvested, ferritin levels determined by ELISA and immunoprecipitated using anti‐ferritin antibodies and the immunoprecipitate examined for the presence of ubiquitin by Western analysis. Cells with the erg6‐2 allele permit the entry of MG132 ( Lee and Goldberg, 1996).",
    "ncbi_link": "erg6‐2: 855003"
  },
  {
    "caption": "A-I. Correlative light electron microscopy (CLEM) showing Prom1 at the plasma membrane of primary hepatocytes. Primary hepatocytes were isolated from 12-week-old male WT (Prom1+/+) or KO ( Prom1cre-ert2-nlacz) mice. The boxed areas in panel (A, D, G) and (B, E, H) were magnified and presented as panel (B, E, H) and (C, F, I), respectively. Scale bar; 5 μm (A, D and G), 1 μm (B, E and H), and 0.2 μm (C, F and I).",
    "ncbi_link": "nlacz: 
cre: 2777477
ert2: 2099
Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice and serum-starved. (K) Differentially expressed genes showing more than a 2-fold change with P < 0.05 (118 DEGs) induced (n=55) or repressed (n=63) by Prom1 knockout (n = 2/group). G6pc, glucose-6-phosphatase catalytic subunit; Pck1, phosphoenolpyruvate carboxykinase 1.",
    "ncbi_link": "G6pc: 14377
glucose-6-phosphatase catalytic subunit: 14377
Pck1: 18534
phosphoenolpyruvate carboxykinase 1: 18534
Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice and serum-starved. (L) Relative expression levels of G6pc and Pck1 mRNAs after serum starvation for 16 hours were determined by qRT-PCR (n = 3/group).",
    "ncbi_link": "G6pc: 14377
Pck1: 18534
Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice and serum-starved. (M) Levels of the Prom1, PCK, G6PC and GAPDH proteins were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice and serum-starved. (N) Prom1+/+ or Prom1-/- hepatocytes serum-starved for 8 hours were incubated with 2-[3H]deoxyglucose for 10 minutes. Glucose uptake was assessed by calculating the amount of cell-associated radioactivity normalized to the amount of protein (n = 3 mice/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "A. Levels of G6pc and Pck1 mRNAs in the liver of mice after 18 hours fasting were determined by qRT-PCR. The level of each mRNA was normalized to the level of 18s rRNA (n = 3/fed, 7 or 8/fasted).",
    "ncbi_link": "18s rRNA: 
G6pc: 14377
Pck1: 18534"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice, serum-starved and stimulated with glucagon. F. Levels of the G6pc and Pck1 mRNAs 2 hours after glucagon stimulation (10 nM) were determined by qRT-PCR. The level of each mRNA was normalized to the level of the 18S rRNA. For these experiments, primary hepatocytes were cultured under 3D conditions using a Matrigel matrix (n = 3 mice/group).",
    "ncbi_link": "18S rRNA: 
G6pc: 14377
Pck1: 18534
Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice, serum-starved and stimulated with glucagon. G. Levels of phospho-PKA substrates (p-PKA substrates), phospho-CREB (p-CREB), CREB, phospho-Inositol trisphosphate receptor (p-IP3R), IP3R, phospho-Hormone-Sensitive Lipase (p-HSL), HSL, Prom1 and Gapdh 10 minutes after glucagon stimulation (10 nM) were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice, serum-starved and stimulated with glucagon. H. The nuclear localization of p-CREB 10 minutes after glucagon stimulation (10 nM) was determined by immunofluorescence staining. Scale bar, 20 μm.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice, serum-starved and stimulated with glucagon. I. Relative PKA activities 10 minutes after glucagon stimulation (10 nM) were determined using the PKA assay kit in the absence or presence of 10 μM IBMX (n = 3 mice/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male Prom1+/+ (WT) or Prom1-/- (KO) mice, serum-starved and stimulated with glucagon. J. The cAMP concentration 10 minutes after glucagon stimulation (10 nM) was determined using the cAMP assay kit in the absence or presence of 10 μM IBMX (n = 3 mice/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with glucagon. (A) Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon stimulation (200 µg/kg body weight, n = 10/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with glucagon. (B) Levels of p-PKA substrates, p-CREB, CREB and GAPDH in the liver after a 5 minutes glucagon treatment were determined by immunoblotting (2 mg/kg body weight).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with glucagon. (C) Relative PKA activities in the liver after a 5 minutes glucagon treatment were determined using the PKA assay kit (2 mg/kg body weight, n = 3/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with glucagon. (D) The cAMP concentration in the liver after a 5 minutes glucagon treatment was determined using the cAMP assay kit (2 mg/kg body weight, n = 3/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice, serum-starved for 16 hours and stimulated with isoprenaline. (H) The nuclear localization of p-CREB after isoprenaline stimulation (10 μM) for 10 minutes was determined by immunofluorescence staining. Scale bar, 20 μm.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice, serum-starved for 16 hours and stimulated with isoprenaline. (I) Levels of p-PKA substrates, p-CREB, CREB, Prom1 and GAPDH after isoprenaline stimulation (10 μM) for 0, 10 or 20 minutes were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were isolated from 12-week-old male WT ( Prom1+/+) and KO (Prom1-/-) mice, serum-starved for 16 hours and stimulated with isoprenaline. (J) The cAMP concentration after isoprenaline stimulation (10 μM) for 10 minutes was determined using the cAMP assay kit in the presence of 10 μM IBMX (n = 3/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "WT (Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with epinephrine (3µg/10g). (K) Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after epinephrine stimulation",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "WT (Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and intraperitoneally injected with epinephrine (3µg/10g). (L) Levels of p-PKA substrates, p-CREB, CREB and GAPDH in the liver 15 minutes after epinephrine treatment were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "M-O. WT (Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and subjected to immobilization test. (M) Blood glucose levels (mg/dL) were measured 0, 60 and 120 minutes after immobilization (n = 10/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "WT (Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and subjected to immobilization test. (N) Levels of p-PKA substrates, p-CREB, CREB and GAPDH in the liver after a 30 minutes-immobilization were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "WT (Prom1+/+) and KO (Prom1-/-) mice were fasted for 4 hours and subjected to immobilization test. (O) Serum epinephrine level of mice after a 30 minutes-immobilization was determined (n = 3/control group, 7 or 8/immobilized group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "A. The expression of Prom1, radixin, AKAP7, AKAP8, AKAP8I, AKAP9, AKAP10, AKAP12 or AKAP13 was silenced in WT hepatocytes using siRNAs. Hepatocytes were then serum-starved for 18 hours and stimulated with glucagon (10 nM) for 10 minutes. The phosphorylation of PKA substrates was determined by immunoblotting.",
    "ncbi_link": "AKAP10: 56697
AKAP12: 83397
AKAP13: 75547
AKAP7: 432442
AKAP8: 56399
AKAP8I: 54194
AKAP9: 100986
Prom1: 19126
radixin: 19684"
  },
  {
    "caption": "Prom1 and radixin expression were silenced in WT (Prom1+/+) and KO (Prom1-/-) hepatocytes by infection with an adenovirus harboring sh-control (sh-Con), sh-radixin (sh-Rdx) or sh-Prom1 for 24 hours. Hepatocytes were further serum-starved for 18 hours and stimulated with glucagon (10 nM) for 10 minutes. (B) The nuclear localization of p-CREB after glucagon stimulation was determined by immunofluorescence staining. Blue; DAPI, Red; p-CREB. The percentage of cells with nuclear p-CREB staining among more than 300 cells in each group was also statistically analyzed (Figure EV3G). Scale bar, 20 μm.",
    "ncbi_link": "Prom1: 19126
radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "Prom1 and radixin expression were silenced in WT (Prom1+/+) and KO (Prom1-/-) hepatocytes by infection with an adenovirus harboring sh-control (sh-Con), sh-radixin (sh-Rdx) or sh-Prom1 for 24 hours. Hepatocytes were further serum-starved for 18 hours and stimulated with glucagon (10 nM) for 10 minutes. (C) Levels of p-PKA substrates, p-CREB, CREB, p-IP3R, IP3R, Prom1, radixin and GAPDH after glucagon stimulation (10 minutes) were determined by immunoblotting.",
    "ncbi_link": "Prom1: 19126
radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "D. Immunofluorescence staining of Prom1 in mouse liver tranduced with adenoviral particles. Confocal microscope images of WT mouse liver infected with adenovirus harboring sh-Con or sh-Rdx linked with IRES-GFP. Scale bar, 20 μm.",
    "ncbi_link": "GFP.: 
Rdx: 19684"
  },
  {
    "caption": "12-week-old male wild type mice were infected with an adenovirus harboring sh-control (sh-Con) or sh-radixin (sh-Rdx) for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (E) Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon administration (200 µg/kg body weight, n = 10 mice/ group).",
    "ncbi_link": "radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "12-week-old male wild type mice were infected with an adenovirus harboring sh-control (sh-Con) or sh-radixin (sh-Rdx) for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (F) Levels of p-PKA, p-CREB, CREB, radixin and GAPDH in the liver after a 10-minutes glucagon stimulation (2 mg/kg body weight) were determined by immunoblotting.",
    "ncbi_link": "radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "12-week-old male wild type mice were infected with an adenovirus harboring sh-control (sh-Con) or sh-radixin (sh-Rdx) for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (G) Glucose disposal rates in sh-Con or sh-Rdx (radixin) mice were measured using glucose, insulin and pyruvate tolerance tests (n = 10 mice/group).",
    "ncbi_link": "radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "Primary hepatocytes were obtained from 12-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice or KO (Prom1-/-) hepatocytes infected with an adenovirus harboring LacZ (Ad-LacZ) or Prom1 (Ad-Prom1) for 24 hours. The molecular interaction between Prom1 and radixin (A) in these hepatocytes was determined by a proximity ligation assay using anti-Prom1 and anti-radixin antibodies (A)",
    "ncbi_link": "LacZ: 
Prom1: 19126"
  },
  {
    "caption": "Primary hepatocytes were obtained from 12-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice or KO (Prom1-/-) hepatocytes infected with an adenovirus harboring LacZ (Ad-LacZ) or Prom1 (Ad-Prom1) for 24 hours. The molecular interaction between Prom1 and PKA regulatory subunits (B) in these hepatocytes was determined by a proximity ligation assay using anti-Prom1 and anti-PKA regulatory subunits (B), respectively. Scale bar, 20 μm.",
    "ncbi_link": "LacZ: 
Prom1: 19126"
  },
  {
    "caption": "HEK293 cells were transiently transfected with the combination of Prom1-FLAG and Myc-radixin plasmids for 24 hours. The molecular interaction between Prom1-FLAG and Myc-radixin was determined by co-immunoprecipitation using isotype control IgG, anti-Myc (E) antibodies.",
    "ncbi_link": "FLAG: 
Myc: 
Prom1: 8842
radixin: 5962"
  },
  {
    "caption": "HEK293 cells were transiently transfected with the combination of Prom1-FLAG and Myc-radixin plasmids for 24 hours. The molecular interaction between Prom1-FLAG and Myc-radixin was determined by co-immunoprecipitation using isotype control IgG, anti-FLAG (F) antibodies.",
    "ncbi_link": "FLAG: 
Myc: 
Prom1: 8842
radixin: 5962"
  },
  {
    "caption": "G. The cellular localization of radixin and actin in WT (Prom1+/+) and KO (Prom1-/-) hepatocytes was determined by immunofluorescence staining for radixin and phalloidin staining. Scale bar, 20 μm.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "H. Detergent-resistant lipid rafts were isolated from WT (Prom1+/+) and KO (Prom1-/-) mouse liver samples. Levels of the Prom1, radixin (RDX), flotillin and transferrin receptor (TfR) proteins were determined in each fraction after sucrose gradient ultracentrifugation using immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "I. Detergent-resistant lipid rafts were isolated from WT (Prom1+/+) and KO (Prom1-/-) mouse primary hepatocytes after cholesterol depletion by methyl-β-cyclodextrin (mβCD, 30 mM) for 30 minutes at 4 oC. Levels of the Prom1, radixin, flotillin and transferrin receptor proteins were determined in each fraction after sucrose gradient ultracentrifugation using immunoblotting.",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "The molecular interactions between PROM1 and radixin mutants were determined by co-immunoprecipitation with an anti-FLAG antibody. HEK293 cells were co-transfected with plasmids expressing Myc-radixin and various deletion mutants of PROM1-FLAG (A) for 24 hours.",
    "ncbi_link": "FLAG: 
Myc: 
PROM1: 8842
radixin: 5962"
  },
  {
    "caption": "The molecular interactions between PROM1 and radixin mutants were determined by co-immunoprecipitation with an anti-FLAG antibody. HEK293 cells were co-transfected with plasmids expressing PROM1-FLAG and various deletion mutants of Myc-radixin (B) for 24 hours.",
    "ncbi_link": "FLAG: 
Myc: 
PROM1: 8842
radixin: 5962"
  },
  {
    "caption": "C. The molecular interaction between PROM1-FLAG and Myc-radixin in the presence of increasing amounts of Myc-FERM was determined by co-immunoprecipitation with an anti-FLAG antibody.",
    "ncbi_link": "Myc: "
  },
  {
    "caption": "WT primary hepatocytes were infected with an adenovirus harboring FERM-Myc (Ad-FERM-Myc) or LacZ (Ad-LacZ) for 48 hours. The cellular localization of radixin was determined by immunofluorescence staining. Scale bar, 20 μm.",
    "ncbi_link": "LacZ: 
Myc: "
  },
  {
    "caption": "WT primary hepatocytes were infected with an adenovirus harboring FERM-Myc (Ad-FERM-Myc) or LacZ (Ad-LacZ) for 48 hours. the nuclear localization of p-CREB after glucagon stimulation for 10 minutes (E) was determined by immunofluorescence staining. Scale bar, 20 μm.",
    "ncbi_link": "LacZ: 
Myc: "
  },
  {
    "caption": "WT primary hepatocytes were infected with an adenovirus harboring FERM-Myc (Ad-FERM-Myc) or LacZ (Ad-LacZ) for 48 hours. (F) Ad-FERM-Myc- or Ad-LacZ-expressing WT hepatocytes were serum-starved for 16 hours and stimulated with glucagon (10 nM) for 10 minutes. Levels of p-PKA substrates, p-CREB, CREB, FERM-Myc and GAPDH were determined by immunoblotting.",
    "ncbi_link": "LacZ: 
Myc: "
  },
  {
    "caption": "Twelve-week-old male wild type mice were infected with an adenovirus harboring GFP or FERM for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (G) Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon stimulation (0.2 mg/kg body weight, n = 10 mice/ group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Twelve-week-old male wild type mice were infected with an adenovirus harboring GFP or FERM for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (H) Levels of p-CREB, CREB, p-PKA substrates, and FERM in the liver 10 minutes after glucagon stimulation (2 mg/kg body weight) were determined by immunoblotting (n = 3 mice/ group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Twelve-week-old male wild type mice were infected with an adenovirus harboring GFP or FERM for 3 days, fasted for 4 hours and intraperitoneally injected with glucagon. (I) Glucose disposal rates in GFP- or FERM-overexpressing mice were measured using glucose, pyruvate and insulin tolerance tests (n = 10 mice/group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) Wild type primary hepatocytes were infected with an adenovirus harboring sh-control (sh-Con), sh-radixin (sh-Rdx), GFP (Ad-GFP), and/or sh-resistant wildtype radixin (Ad-RdxR) or AKAP-dead LPTD mutant of radixin (Ad-LPTDR) for 24 hours.",
    "ncbi_link": "AKAP: 
GFP: 
radixin: 19684
Rdx: 19684"
  },
  {
    "caption": "(B) Increasing amount of Ad-RdxR or Ad-LPTDR were infected to WT primary hepatocytes for 24 hours. Hepatocytes were further serum-starved for 18 hours and stimulated with glucagon (10 nM) for 10 minutes. Levels of p-PKA substrates, p-CREB, CREB, radixin, Myc-radixin and GAPDH were determined by immunoblotting.",
    "ncbi_link": "Rdx: 19684"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (C) DIO WT (Prom1+/+) and KO (Prom1-/-) mice were intraperitoneally injected with glucagon. Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon (100 µg/kg body weight) stimulation (n = 10 mice/ group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (D) Levels of p-PKA substrates, p-CREB, CREB, Prom1 and GAPDH were determined by immunoblotting 10 minutes after glucagon (2 mg/kg body weight) stimulation (n = 3 mice/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (E) Glucose disposal rates in DIO WT (Prom1+/+) and KO (Prom1-/-) mice were measured using glucose and insulin tolerance tests (n = 10 mice/group).",
    "ncbi_link": "Prom1: 19126"
  },
  {
    "caption": "Four-week-old male WT (Prom1+/+) and KO (Prom1-/-) mice were fed a high-fat diet for 8 weeks (Diet-Induced Obesity; DIO), and fasted for 4 hours before experiments. (F) DIO KO (Prom1-/-) mice were infected with an adenovirus harboring LacZ or Prom1 for 24 hours, fasted for 4 hours and intraperitoneally injected with glucagon (100 µg/kg body weight). Blood glucose levels (mg/dL) were measured 0, 15, 30, 60 and 120 minutes after glucagon stimulation (GST). Glucose disposal rates were measured using the pyruvate tolerance test (PTT) (n = 10 mice/group).",
    "ncbi_link": "LacZ: 
Prom1: 19126"
  },
  {
    "caption": "(B) Western blot  of RNAi efficiency and specificity for oligos used in (C-G). HeLa Kyoto cells were incubated for 72 h with control oligos or RNAi-oligos depleting CUL4A, CUL4B  or DDB1. Specific downregulation of the indicated proteins was analyzed by immunoblotting. GAPDH  controls for equal loading. (C) Quantification of  western blot bands and the ratio between neddylated  vs unneddylated CUL4 with the paralog downregulated is calculated. Graphs displays mean with SEM of N=3 biological replicates. **P = 0.001.",
    "ncbi_link": "CUL4A: 8451
CUL4B: 8450
DDB1: 1642"
  },
  {
    "caption": "(A)  Western blot  analysis to monitor CUL4A  or CUL4B  levels in extracts prepared from HeLaFLP  control cells or HeLaFLP  cells deleted for CUL4B by CRISPR/Cas9  (∆CUL4BFLP) but stably expressing no CUL4B  (-), CUL4B  or the indicated NP1 or P50L mutants from the doxycycline-inducible promoter. GAPDH  was included to control equal loading. One of three biological replicates is shown.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
CUL4B: 8450"
  },
  {
    "caption": "(C) To control RNAi efficiency and specificity, HeLa Kyoto cells were incubated for 72 h with control oligos (control) or RNAi-oligos depleting CUL4B, LIS1  or WDR1. Specific downregulation of the indicated proteins was analyzed by immunoblotting. GAPDH  controls for equal loading. One of three biological replicates is shown.",
    "ncbi_link": "CUL4B: 8450
LIS1: 5048
WDR1: 9948"
  },
  {
    "caption": "(E) HA-immunoprecipitation  (IP) of extracts (input) prepared from unedited (-) or HA-CUL4B  endogenously expressing HeLa Kyoto  cell lines arrested in S-phase (thymidine) or mitosis  (nocodazole) were probed with antibodies against LIS1, WDR1  and DDB1. The antibody recognizing phospho-H3(S19) controls mitotic  arrest and specificity of the immunoprecipitation.",
    "ncbi_link": "HA: 
CUL4B: 8450"
  },
  {
    "caption": "(F, G)  HeLa Kyoto  endogenously expressing HA-CUL4B  or the indicated NP1 or P50L mutants were arrested in mitosis with nocodazole. Extracts (input) and HA-immunoprecipitants  were analyzed for the presence of HA-CUL4B  for control and bound DDB1  and LIS1  (F) or DDB1  and WDR1  (G), respectively. One of 3 biological replicates is shown.",
    "ncbi_link": "HA: 
CUL4B: 8450"
  },
  {
    "caption": "(C) Extracts (input) prepared from S-phase (S; thymidine) or mitosis  (M; nocodazole)-arrested  HeLa Kyoto  cells (-) and endogenously expressing HA-tagged WT CUL4B, or the NP1 or P50L mutants were immunoprecipitated  with HA.II-antibodies (IP). Bound ACTR3  or DDB1  was detected using specific antibodies. One of three biological replicates is shown. Note that in contrast to DDB1, ACTR3 binds CUL4B  in a phosphorylation-dependent manner.",
    "ncbi_link": "HA: 
CUL4B: 8450"
  },
  {
    "caption": "(D) HA-immunoprecipitants   (IP) of extracts (input) prepared from unedited (-) controls or endogenously expressing HA-CUL4B HeLa Kyoto  cells arrested in mitosis  with nocodazole  were probed with antibodies against DDB1, DCTN1  (dynactin) and actin. One of two biological replicates is depicted.",
    "ncbi_link": "HA: 
CUL4B: 8450"
  },
  {
    "caption": "(F) Live cell imaging of HeLa  cells expressing H2B-mcherry   and lifeAct-GFP, treated for 72 h with control oligos (siControl) or RNAi-oligos depleting CUL4B, LIS1  or WDR1. Representative cells are shown in time  intervals of 6 min during metaphase with identical contrast settings. The unanchored spindle  in CUL4B- and LIS1  deleted cells is marked with a white arrow. Scale bar: 10 μm.",
    "ncbi_link": "CUL4B: 8450
LIS1: 5048
WDR1: 9948"
  },
  {
    "caption": "hESCs  were differentiated to generate human forebrain  specific regionalised organoids. Sections were stained  as indicated with antibodies against SOX2  or CTIP2  to visualize neural stem cell  and neuronal cell populations, respectively. (A) Example images of day 35 organoids. The stained  sections are also shown as merged images at different maginifications, with scale bars of 200 μm and 50 μm, respectively. (B) The number of cortical  units per mm2 total area was quantified in unedited and ΔCUL4B brain  organoids at day 35. Ventricles  were counted and the number divided by the total organoid area on 20 sections from one biological replicate.",
    "ncbi_link": "CUL4B: 8450"
  },
  {
    "caption": "A Time course images of the hippocampal CA1 region of Siglechdtr/dtr mice after DT administration. Sections were stained with an anti-Iba1 antibody (green) and DAPI (cyan). Arrow: live microglia with normal nucleus. Double arrow: apoptotic microglia with pyknotic nucleus. Arrowhead: microglial debris with no nucleus. Scale bar, 50 µm. B Number of apoptotic microglia with pyknotic or fragmented nucleus (n = 5 animals per group, Kruskal-Wallis test with post hoc Dunn's test). C Number of live microglia with normal nucleus (n = 5 animals per group, one-way ANOVA with post hoc Tukey's test). D Number of pieces of microglial debris (Iba1+ spheres with a diameter > 2 µm and no nucleus) (n = 5 animals per group, Kruskal-Wallis test with post hoc Dunn's test). ",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "E A representative image of a survived microglial cell in the hippocampal CA1 region of Siglechdtr/dtr mice 2 days after DT administration. Sections were stained with an anti-Iba1 antibody (green) and DAPI (cyan). A 3D image (rightmost panel) was reconstructed using Imaris software. Arrow: live microglia. Arrowhead: microglial debris. Scale bar, 10 µm.",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "A Histological analysis of RFP+ cells in Siglechdtr/dtr:Ccr2RFP/+ mice. Lumber spinal cord after EAE induction, and hippocampal CA1 2 or 4 days after PBS or DT injection were analyzed. Iba1 immunoreactivity (green) and RFP fluorescence (red) are shown. Images were acquired using the same laser power and sensitivity, and image processing was the same for all RFP signals (red). Scale bar, 50 µm.",
    "ncbi_link": "RFP: 
Ccr2: 12772
dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "B Flow cytometric analysis of RFP+Ly6Chigh inflammatory monocytes in peripheral blood of Siglechdtr/dtr:Ccr2RFP/+ mice 2 days after PBS or DT administration. Representative data and a quantification graph (n = 5 animals per group, two-tailed unpaired Student's t-test) are shown.",
    "ncbi_link": "RFP: 
Ccr2: 12772
dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "C Immunohistochemical localization of CD206+ perivascular macrophages (arrows) in hippocampal CA1 of Siglechdtr/dtr mice. Sections prepared 2 days after administration of PBS or DT were stained with anti-Iba1 (green), anti-CD206 (red) and anti-CD31 (blue) antibodies. Scale bar, 50 µm. D Number of perivascular macrophages in hippocampal CA1 of Siglechdtr/dtr mice 2 days after PBS or DT administration (n = 5 animals per group, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "A qPCR analysis of marker molecules for CNS cell types. The hippocampus of WT and Siglechdtr/dtr mice 2 days after PBS or DT administration was analyzed (n = 3 animals per group, one-way ANOVA with post hoc Tukey's test). Results are normalized to Gapdh, and are shown as ratios to the value of WT mice injected with PBS.",
    "ncbi_link": "Gapdh: 14433
dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "B Immunohistochemical detection of astrocytes in Siglechdtr/dtr mice. Hippocampal CA1 sections were prepared 2 days after PBS or DT administration, and stained with an anti-GFAP antibody. Images were acquired using the same laser power and sensitivity, and image processing was the same. Scale bar, 30 µm. C Astrocyte number in hippocampal CA1 of Siglechdtr/dtr mice 2 days after PBS or DT administration (n = 5 animals, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "A Representative images of microglial debris surrounded by astrocyte processes in hippocampal CA1. Sections were prepared from Siglechdtr/dtr mice 2 days after PBS or DT administration, and stained with anti-GFAP (green) and anti-CD11b (red) antibodies. 3D images (lower row) were reconstructed from confocal images (upper row) using Imaris software. Scale bar, 10 µm.",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "B CLEM analysis of a phagocytic astrocyte in hippocampal CA1 of Siglechdtr/dtr mice 2 days after DT administration. A phagocytic astrocyte, which engulfed degenerated microglial components, was identified by immunohistochemistry using anti-S100β (green) and anti-CD11b (red) antibodies, and DAPI (cyan) (upper and middle panels). Then, a phagocytic cup of the same cell was analyzed by electron microscopy (lower panel). Degenerated microglial cytoplasm/plasma membrane (arrow) and nucleus (double arrow) in a phagocytic cup of the astrocyte, and a piece of microglial debris internalized in astrocytic cytoplasm (arrowhead) are indicated. Scale bar, 50 µm (upper panel), 10 µm (upper panel [inset] and middle panel), and 2 µm (lower panel).",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "C A representative image of a phagocytic astrocyte in hippocampal CA1 of Siglechdtr/dtr mice 2 days after DT administration. Sections were stained with anti-S100β (green) and anti-CD11b (red) antibodies, and confocal images were reconstructed using Imaris software. The lower two panels are higher magnification images of contacted microglial debris. Arrow: microglial debris contacted by astrocyte processes (coverage: approximately 30 or 50%). Arrowhead: microglial debris internalized in astrocyte cytoplasm. Scale bar, 10 µm (upper panel) and 2 µm (lower panels). D, E Quantification of the pieces of debris (CD11b+ spheres with > 0.5 µm diameter) contacted with (coverage > 30%) (D) and internalized by (E) a single astrocyte within 30 µm-thick sections (n = 75 cells from five animals per group). The number of debris pieces was counted in 3D images reconstructed using Imaris software. All confocal images were acquired using the same laser power and sensitivity, and image processing was the same.",
    "ncbi_link": "dtr: 15200
Siglech: 233274"
  },
  {
    "caption": "Cultured astrocytes engulf microglial debris. CAG-EGFP mouse-derived primary astrocytes were co-cultured with or without fluorescence-labelled apoptotic microglia. (A) Fluorescence images of GFP (green), microglial debris (red) and GFAP immunoreactivity (blue). Images were acquired using the same laser power and sensitivity, and image processing was the same in the two images (red). Scale bar, 50 µm.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "D Expression of TAM family members and their knockdown by siRNA in cultured astrocytes. Tyro3, Axl and Metk in cultured astrocytes or hippocampal tissue were examined by western blotting. Arrows indicate the corresponding protein band(s). The secondary antibody against goat IgG generates a ~115 kDa non-specific band. The ~115 kDa band in the Axl image is the Axl-specific band overlapping the non-specific band. The ~115 kDa band in the Mertk image is the non-specific band. Axl and Mertk expression was knocked down by two siRNAs. GAPDH expression is shown as an internal control. E Quantification of siRNA knockdown in cultured astrocytes (n = 3 independent experiments, one-way ANOVA with repeated measures). Knockdown of Tyro3 mRNA was examined by qPCR because of the very low expression level even in control astrocytes. Knockdown efficiency of Axl and Mertk was quantified from western blots. Results are normalized to Gapdh or GAPDH, and are shown as ratios to the value of non-transfected astrocytes.",
    "ncbi_link": "Axl: 26362
GAPDH: 14433
Mertk: 17289
Tyro3: 22174"
  },
  {
    "caption": "B Representative images of microglial distribution in the cerebral cortex of WT and mutant mice at 3 w. Sections were stained with anti-Iba1 or anti-CD11b antibodies (red). Scale bar, 100 µm. C Quantification of microglial number (n = 5 animals per group, one-way ANOVA). Note that Irf8-/- mice were analyzed by CD11b immunostaining, while other strains were analyzed by Iba1 staining. ",
    "ncbi_link": "Irf8: 15900"
  },
  {
    "caption": " D Representative images of a spontaneous apoptotic cell and surrounding glial cells in the cerebral cortex of WT and Irf8-/- mice at 3 w. Sections were stained with anti-GFAP (green), anti-CD11b (red) and anti-cleaved caspase-3 (blue) antibodies. 3D images (lower row) were reconstructed from confocal images (upper row) using Imaris software. Arrows indicate cleaved caspase-3+ apoptotic cells. Insets are higher magnification images around apoptotic cells. Scale bar, 20 µm and 5 µm (insets). E Percentage of spontaneous apoptotic cells surrounded by microglia in WT and mutant mice. 3D images reconstructed from confocal images were analyzed (n = 36-50 cells from five animals per group, Kruskal-Wallis test with post hoc Dunn's test). F Percentage of spontaneous apoptotic cells surrounded by astrocyte processes in WT and mutant mice (n = 36-50 cells from five animals per group, one-way ANOVA with post hoc Tukey's test). ",
    "ncbi_link": "Irf8: 15900"
  },
  {
    "caption": "(C) Western blot analysis of cells transfected with 10 nM siRNA against ERK1, ERK2 or a 5 nM combination of each (ERK1+2).",
    "ncbi_link": "ERK2: 26413
ERK1: 26417"
  },
  {
    "caption": "(a) Lysates extracted from the SVZ of three different Ctrl and FIP200GFAP cKO mice treated with chloroquine, and then analyzed by western blot using antibodies to LC3 (top), p62 (middle) or vinculin (bottom).",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(b) Immunofluorescence for p62 and DAPI in the SVZ and DG of Ctrl and FIP200GFAP cKO mice at P28 (n = 3 p62 for each). Dotted lines indicate boundaries of the SVZ and granular zone (GZ). The arrows and arrowheads mark larger and smaller p62+ aggregates, respectively, in the striatum (ST) and SVZ.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(c) TEM of mitochondria in SVZ tissue from Ctrl and FIP200GFAP cKO mice at P28 and P56 (n = 2 mice for each, >30 cells for each mouse). Arrows mark mitochondria.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(d) TEM of mitochondria in cultured neurospheres from Ctrl and FIP200GFAP cKO mice (n = 2 mice for each, >30 cells for each mouse). Arrows mark mitochondria.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(e,f) DHE and DAPI fluorescence in the dentate gyrus (e) and SVZ (f) of Ctrl and FIP200GFAP cKO mice at P28 (n = 5 mice for each). Dotted lines indicate the boundaries of the GZ (e) and SVZ (f). Arrows mark cells in the SGZ (e) and SVZ (f), and arrowheads mark cells in surround regions (the GZ in e and the ST in f). LV, lateral ventricle; ML, molecular layer. Full-length blots are presented in Supplementary Figure 11.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(a) Lysates extracted from the SVZ of three different Ctrl and FIP200GFAP cKO mice treated with chloroquine, and then analyzed by western blot using antibodies to LC3 (top), p62 (middle) or vinculin (bottom).",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(a) Hematoxylin and eosin staining of the dentate gyrus (DG) and SVZ from Ctrl and FIP200GFAP cKO mice at P28. Lines indicate the boundaries of the DG and SVZ. Arrows mark cells in the SVZ.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(b-e) Immunofluorescence for GFAP, nestin or SOX2 and DAPI in the DG (b,c) from Ctrl and FIP200GFAP cKO mice at P28. The boxed areas in c-e are shown in more detail in insets (c). Dotted lines indicate boundaries of the granular zone (GZ) and SGZ (b). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (b,c), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(b-e) Immunofluorescence for GFAP, nestin and DAPI in the SVZ (d,e) from Ctrl and FIP200GFAP cKO mice at P28. The boxed areas in c-e are shown in more detail in panels below (d,e). Dotted lines indicate boundaries of the SVZ (d,e). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (b,c), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(b-e) Immunofluorescence for GFAP, nestin or SOX2 and DAPI in the SVZ (d,e) from Ctrl and FIP200GFAP cKO mice at P28. The boxed areas in c-e are shown in more detail in panels below (d,e). Dotted lines indicate boundaries of the SVZ (d,e). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (b,c), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(f) Immunofluorescence for PSA-NCAM in the RMS (boxed areas), SVZ and DG of Ctrl and FIP200GFAP cKO mice at P28. Lines indicate the boundaries of the DG and SVZ. Arrows mark PSA-NCAM+ cells in the RMS, SVZ and DG.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(g) Immunofluorescence for NeuN in the olfactory bulb (OB) and DG of Ctrl and FIP200GFAP cKO mice at P31. Lines indicate the layers of the OB and boundaries of the DG. Boxed areas in top panels are shown in more detail for staining of NeuN in insets. CC, corpus callosum; E, ependymal cells; LV, lateral ventricle; ML, molecular layer; ST, striatum; IGL, internal granular layer; MCL, mitral cell layer; EPL, external plexiform layer; GL, glomerular layer.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(a-e) Primary (1st) and secondary (2nd) neurospheres from Ctrl and FIP200GFAP cKO mice at P0 and P28. Representative P0 phase contrast images are shown in a. Mean ± s.e.m. of number (b,d) and size (c,e) of primary and secondary neurospheres from three independent experiments are shown (n = 3 mice for each).",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(f) Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DAPI staining of the SVZ and dentate gyrus (DG) from Ctrl and FIP200GFAP cKO mice at P28. Lines indicate the boundaries of the SVZ. Numbered boxed areas are shown in more detail as insets for staining of TUNEL and DAPI in the SVZ and DG.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(g) Short-term BrdU incorporation in the SVZ and DG of Ctrl and FIP200GFAPcKO mice at P28. Dotted lines indicate the boundaries of the SVZ and granular zone (GZ). Boxed areas are shown in more detail in the insets. Lines indicate the boundaries of the SVZ and GZ. Arrows mark BrdU+ cells. CC, corpus callosum; LV, lateral ventricle; ST, striatum. *P 0.05; **P 0.01; ***P 0.001.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(h) Long-term retention of BrdU in the SVZ and dentate gyrus of Ctrl and FIP200GFAP cKO mice at P31. Lines indicate the boundaries of the SVZ and GZ. Arrows mark BrdU+ cells. CC, corpus callosum; LV, lateral ventricle; ST, striatum. *P 0.05; **P 0.01; ***P 0.001.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421"
  },
  {
    "caption": "(a) Lysates extracted from neurospheres of Ctrl, FIP200GFAP cKO, Trp53GFAP cKO and 2cKO mice and analyzed by western blot using antibodies to p53 and actin.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421
Trp53: 22059"
  },
  {
    "caption": "(b) Mean ± s.e.m. of relative mRNA level (normalized to Ctrl mice as 1) of Cdkn1a, Bbc3, Fas, Pax6 and Stat3 in neurospheres of Ctrl, FIP200GFAP cKO, 2cKO and Trp53GFAP cKO mice are shown (n = 3 mice for each).",
    "ncbi_link": "Bbc3: 170770
Cdkn1a: 12575
Fas: 14102
GFAP: 14580
Pax6: 18508
FIP200: 12421
Stat3: 20848
Trp53: 22059"
  },
  {
    "caption": "(c,d) Mean ± s.e.m. of the number (c) and size (d) of primary and secondary neurospheres from Ctrl, FIP200GFAP cKO, 2cKO and Trp53GFAP cKO mice at P28 (n = 3 mice for each).",
    "ncbi_link": "GFAP: 14580
FIP200: 12421
Trp53: 22059"
  },
  {
    "caption": "(e-h) Analysis of immunofluorescence or staining on frozen-sectioned neurospheres for nestin, Ki67, TUNEL, PAX6, phosphorylated STAT3 (pSTAT3) and DAPI, as indicated. Mean ± s.e.m. of the percentage of Ki67+ (e), BrdU+ (f) and TUNEL+ (g) cells in neurospheres from Ctrl, FIP200GFAP cKO, 2cKO and Trp53GFAP cKO mice are shown (n = 3 mice for each, counting of >500 cells for each mouse). Representative images are shown in h. *P 0.01. Full-length blots are presented in Supplementary Figure 11.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421
Trp53: 22059"
  },
  {
    "caption": "(d-m) Immunofluorescence of the DG (d-h) of P28mice (d,e,i,j). Boxed areas are shown in more detail in insets (e,j) and/or panels below (i,j). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (d,e), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes. Mean ± s.e.m. of the number of GFAP+nestin+ and GFAP+SOX2+ radial glia (f,h), and NSCs (k,m), and GFAP+nestin− astrocytes (g,l) per section are shown. Dotted lines indicate the boundaries of the SVZ and DG (a,i,j,p) or granular zone (GZ; d,e,p). E, ependymal cells; LV, lateral ventricle; ML, molecular layer; ST, striatum. NS, not significant; *P 0.05; **P 0.01; ***P 0.001",
    "ncbi_link": "GFAP: 14580"
  },
  {
    "caption": "(d-m) Immunofluorescence of the SVZ (i-m) of P28mice (d,e,i,j). Boxed areas are shown in more detail in insets (e,j) and/or panels below (i,j). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (d,e), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes. Mean ± s.e.m. of the number of GFAP+nestin+ and GFAP+SOX2+ radial glia (f,h), and NSCs (k,m), and GFAP+nestin− astrocytes (g,l) per section are shown. Dotted lines indicate the boundaries of the SVZ and DG (a,i,j,p) or granular zone (GZ; d,e,p). E, ependymal cells; LV, lateral ventricle; ML, molecular layer; ST, striatum. NS, not significant; *P 0.05; **P 0.01; ***P 0.001",
    "ncbi_link": "GFAP: 14580"
  },
  {
    "caption": "(s,t) Mean ± s.e.m. of percentage of GFAP+nestin+BrdU+ cells of total BrdU retained cells in the SVZ (s) and SGZ (t) of P31mouse. n = 5 mice, ≥4 sections per mouse, >500 cells counted per mouse in n, >20 BrdU+ cells counted per mouse.",
    "ncbi_link": "GFAP: 14580"
  },
  {
    "caption": "(g-i) Immunofluorescence of BrdU retention cells in the DG and OB of P31 mice. Boxed areas in left column of g are shown in more detail in right column. Dotted lines indicate the boundaries of the DG (left) and GZ (right). Arrows mark NeuN+BrdU+ cells and arrowheads mark NeuN−BrdU+ cells in the DG. Mean ± s.e.m. of the percentage of NeuN+BrdU+ cells of total BrdU retained cells in the DG (h) and OB (i) are shown. (j,k) Mean ± s.e.m. of percentage of GFAP+nestin−BrdU+ cells among total BrdU+ retained cells in the SVZ (j) and SGZ (k).",
    "ncbi_link": "GFAP: 14580"
  },
  {
    "caption": "(l,m) DHE and DAPI fluorescence at P28 in the DG (l) and SVZ (m) from FIP200GFAP cKO mice with or without NAC treatment, 2cKO mice and Trp53GFAP cKO mice. Dotted lines indicate the boundaries of the granular zone (GZ) (l) and SVZ (m). Arrows mark cells in the SGZ (l) and SVZ (m) and arrowheads mark cells in surrounding regions (the GZ in l and the striatum (ST) in m). n = 5 mice, ≥4 sections per mouse, >20 (h,j,k) or >200 (i) BrdU+ cells counted per mouse. cKO(n), NAC non-responder cKO mice; LV, lateral ventricle; ML, molecular layer; IGL, internal granular layer; MCL, mitral cell layer; EPL, external plexiform layer; GL, glomerular layer. NS, not significant; *P 0.05.",
    "ncbi_link": "GFAP: 14580
FIP200: 12421
Trp53: 22059"
  },
  {
    "caption": "(d-m) Immunofluorescence of the DG (d-h) and SVZ (i-m) of P28 mice treated by NAC or vehicle control. Representative images are shown in d,g (DG) and k,m (SVZ). Dotted lines indicate boundaries of the granular zone (GZ) (d,g) and SVZ (k,m). Boxed areas in g,k,m are shown in more detail in insets (g,m) and/or panels below (k,m). Lines indicate boundaries of the GZ (d,g) and SVZ (k,m). Arrows mark GFAP+nestin+ and GFAP+SOX2+ NSCs with radial glial morphology (d,g), and arrowheads mark GFAP+nestin− and GFAP+SOX2− astrocytes. Mean ± s.e.m. of the number of GFAP+nestin+ and GFAP+SOX2+ radial glia (e,h), and NSCs (i,l), and GFAP+nestin− astrocytes (f,j) per section are shown. (n,o) Mean ± s.e.m. of the number of TUNEL+ cells per 100 SVZ cells (n) or per 1 mm2 DG area (o) of P28mice treated by NAC or vehicle control. n = 5 mice, ≥4 sections per mouse, >500 cells counted per NAC in n. cKO(n), NAC non-responder cKO mice; E, ependymal cells; LV, lateral ventricle; ML, molecular layer; ST, striatum. **P 0.01.",
    "ncbi_link": "GFAP: 14580"
  },
  {
    "caption": "A Kinetics of intracellular Ca2+ after EDN stimulation. UACC257 and A2058 (WT and ENDRB-KO) were seeded on 96 well plates, loaded with Fluo-4 dye and stimulated with 100 nM EDN or PBS. Fluo-4 fluorescence was monitored over ten minutes (n = 6). Representative example of three independent experiments.",
    "ncbi_link": "ENDRB: 1910"
  },
  {
    "caption": ", Total protein levels of Munc18-1. HEK293T cells transfected with WT or mutant Munc18-1 variants and either GFP, syntaxin-11-264 or syntaxin-11-180 were lysed and lysates were analyzed by quantitative immunoblotting to indicated proteins, normalized to β-actin (Synt-1A = syntaxin-1A). Data are means ± SEM (*p < 0.05, **p < 0.01, ***p < 0.001, ****p<0.0001 by Kruskal-Wallis test, followed by Dunn's multiple comparison test; n = 11 independent experiments; exact p values are shown in Appendix Table S1).",
    "ncbi_link": "syntaxin-1: 116470
Munc18-1: 6812"
  },
  {
    "caption": "Solubility of Munc18-1. HEK293T cells transfected as in (C) were solubilized in 0.1% Triton X-100 (TX) and equal volumes of soluble and insoluble fractions were analyzed by quantitative immunoblotting. TX-soluble Munc18-1 was measured as percent of total Munc18-1 by quantitative immunoblotting. Data are means ± SEM (*p<0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by Kruskal-Wallis test followed by Dunn's multiple comparison test, or by one-way ANOVA followed by Bonferroni post-hoc test; n = 5-9 independent experiments; exact n and p values are shown in Appendix Table S1).",
    "ncbi_link": "Munc18-1: 6812"
  },
  {
    "caption": "Munc18-1 knockout neurons expressing G544D Munc18-1 were subjected to analysis of mean firing rate before addition of compounds (0 h) or 48 hours after vehicle (DMSO) or compound addition. 16 electrodes per well were analyzed for neuronal firing (A; purple boxes indicate network activity). Data are means ± SEM (*p < 0.05, **p < 0.01, ***p < 0.001 by one-way ANOVA and Dunnett's multiple comparison test, or Kruskal-Wallis test followed by Dunn's post-hoc test; n = 11-16 independent experiments; exact n and p values are shown in Appendix Table S1).",
    "ncbi_link": "Munc18-1: 25558"
  },
  {
    "caption": "Uptake of synaptotagmin-1 antibody during high K+ stimulation. Neurons expressing cre recombinase and/or WT, R406H or G544D Munc18-1b with or without compound were subjected 7 days after lentiviral infection to an antibody uptake assay. Endocytosed synaptotagmin-1 antibody was quantified by immunostaining (A-C; scale bar = 30 µm; 4-PBA = 4-phenylbutyrate), via counting the number of pixels > intensity of 15 (D). Data are means ± SEM (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by one-way ANOVA and Dunnett's multiple comparison test; n = 3-10 independent experiments; exact n and p values are shown in Appendix Table S1).",
    "ncbi_link": "cre: 2777477
Munc18-1b: 20911"
  },
  {
    "caption": "Rescue of the subcellular localization of UNC-18 in worms expressing G544D UNC-18. C. elegans expressing WT::GFP or G544D::GFP were immobilized, and the ventral nerve cord was imaged. Solid arrowheads point to pairs of bigger puncta, broken arrowheads to single, smaller puncta (N, O). Scale bar in (N) and (O) = 10 µm. 4-PBA = 4-phenylbutyrate.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Rescue of the subcellular localization of UNC-18 in worms expressing G544D UNC-18. C. elegans expressing WT::GFP or G544D::GFP at 1, 5, 20 or 100 µM compound were immobilized, and the ventral nerve cord was imaged. Solid arrowheads point to pairs of bigger puncta, broken arrowheads to single, smaller puncta",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A-F Indirect calorimetry was performed using the Oxymax/CLAMS system in Cdk4+/+ (n=6) and Cdk4-/- (n=5) mice. Whole-body oxygen consumption rate (VO2) (A-B), energy expenditure (EE) (C-D) and respiratory exchange ratio (RER) (E-F) were measured at 24°C and during a cold challenge at 6°C during both the light (white rectangle) and dark (black rectangle) phases over a 2-day period.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "J-K Basal rectal temperature was measured at 24°C (J), and rectal temperature was monitored during acute cold exposure at 4°C for 6 hours (K) in Cdk4+/+ (n=10) and Cdk4-/- (n=8) mice.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "A Gross morphology of iBAT from Cdk4+/+ and Cdk4-/- mice.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "C Hematoxylin-eosin staining and UCP1 immunohistochemical (IHC) staining of iBAT sections (scale bar 100 μm) from Cdk4+/+ and Cdk4-/- mice.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "F Expression of thermogenic genes and brown adipocyte markers in iBAT of Cdk4+/+ (n=6) and Cdk4-/- (n=6) mice as assessed by RT-PCR.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "G-H Transmission electron microscopy (TEM) images of iBAT (G) (scale bar 5 μm (upper panel) and 1 μm (lower panel, LD indicates lipid droplet and M mitochondria)) and quantification of lipid droplet number (LD) and mitochondrial volume (Mito) (H) (Cdk4+/+ (n=4) and Cdk4-/- (n=4)).",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "I Respirometry analysis of iBAT as measured by the Oroboros system (Cdk4+/+ (n=6) and Cdk4-/- (n=6)).",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "A-B Rectal temperature was measured at 24°C (A), and rectal temperature was monitored for 6 hours during acute cold exposure at 4°C (B) in Cdk4flox/flox (n=9) and Cdk4flox/flox Ucp1-Cre mice (n=9).",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Ucp1: 22227"
  },
  {
    "caption": "C Gross morphology of iBAT from Cdk4flox/flox and Cdk4flox/flox Ucp1-Cre mice D iBAT mass compared to body weight of Cdk4flox/flox (n=8) and Cdk4flox/flox Ucp1-Cre (n=7) mice. ",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Ucp1: 22227"
  },
  {
    "caption": "E Hematoxylin-eosin (H&E) staining and UCP1 immunohistochemical (IHC) staining of iBAT sections (scale bar 100 μm (upper panel) and 50 μm (lower panel)) from Cdk4flox/flox and Cdk4flox/flox Ucp1-Cre mice.",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Ucp1: 22227"
  },
  {
    "caption": "H Expression of thermogenic genes and brown adipocyte markers in iBAT of Cdk4flox/flox (n=5) and Cdk4flox/flox Ucp1-Cre (n=6) mice as assessed by RT-PCR.",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Ucp1: 22227"
  },
  {
    "caption": "A-B TH immunohistochemical staining in iBAT sections (A) (scale bar 20 μm, arrows indicate TH parenchymal fibers) and corresponding quantification of the number of TH fibers relative to 100 adipocytes (B) (Cdk4+/+ (n=6) and Cdk4-/- (n=6)).",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "C Hematoxylin-eosin staining in scWAT showing multilocular adipocytes in Cdk4-/- (scale bar 50 μm).",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "D Expression of thermogenic genes and brown adipocyte markers in scWAT of Cdk4+/+ (n=5) and Cdk4-/- (n=6) mice as assessed by RT-PCR.",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "E-F Acute cold test (4°C) after treatment with the β-adrenergic antagonist propranolol (Prop) in Cdk4+/+ (n=7) and Cdk4-/- (n=6) animals or with vehicle (NaCl) (Cdk4+/+ (n=7) and Cdk4-/- (n=6)) (E) and corresponding quantification of the area under the curve (AUC).",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "A Cdk4 mRNA expression in the dissected VMH of Cdk4flox/flox (n=5) and Cdk4flox/flox Sf1-Cre (n=6) mice",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Sf1: 26423"
  },
  {
    "caption": "B-C Rectal temperature was measured at 24°C (B), and rectal temperature was monitored during acute cold exposure at 4°C for 6 hours (C) in Cdk4flox/flox (n=15) and Cdk4flox/flox Sf1-Cre mice (n=15).",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Sf1: 26423"
  },
  {
    "caption": "D Hematoxylin-eosin (H&E) staining of iBAT sections (scale bar 100 μm) from Cdk4flox/flox and Cdk4flox/flox Sf1-Cre mice.",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Sf1: 26423"
  },
  {
    "caption": "E Expression of thermogenic genes and brown adipocyte markers expression in iBAT Cdk4flox/flox (n=9) and Cdk4flox/flox Sf1-Cre mice (n=9) mice as assessed by RT-PCR.",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Sf1: 26423"
  },
  {
    "caption": "F-G TH immunohistochemical (IHC) staining in iBAT sections (F) (scale bar 40 μm, arrows indicate TH parenchymal fibers) and corresponding quantification of the number of TH fibers relative to 100 adipocytes (G) (Cdk4flox/flox (n=5) and Cdk4flox/flox Sf1-Cre mice (n=5)).",
    "ncbi_link": "Cdk4: 12567
Cre: 2777477
Sf1: 26423"
  },
  {
    "caption": "A-D Confocal illustrations of frontal hypothalamic sections from Cdk4+/+ mice (A, C, N=3) and Cdk4-/- mice (B, D, N=3). Low magnification showing nuclei (Hoechst, left pannel) and c-Fos activated-cells (white, right pannel) in the mPOA (A1-2, B1-2) and the ARC, the VMH, the DMH, the LH (C1-2, D1-2). High magnifications corresponding to the frame area in A1-2, B1-2, C2, D2 and showing c-Fos-IR cells (A3-4, B3-4, C3-6, D3-6). Scale bars (A1-2, B1-2, C1-2, D1-2): 200μm, (A3-4, B3-4, C3-4, D3-4): 50μm. E Quantification of c-Fos IR cells in brain sections of Cdk4+/+ and Cdk4-/- mice (n=15-24 slices according hypothalamic nucleus and genotype). ",
    "ncbi_link": "Cdk4: 12567"
  },
  {
    "caption": "(H) Bar plot of measured extracellular pBB275 plasmid concentration at 0 hr and 6 hr in the co-culture composed of E. coli MG1655-rfp and B. subtilis.",
    "ncbi_link": "rfp: "
  },
  {
    "caption": "(B, C) (B) Extracellular pBB275 plasmid concentration or (C) extracellular E. coli genomic DNA concentration at 0 or 6 hr in the co-cultures composed of a recA+ or recA- E. coli plasmid donor and engineered B. subtilis.",
    "ncbi_link": "recA: 947170"
  },
  {
    "caption": "(C) Scatter plot of the initial abundance of heat-killed E. coli MG1655-rfp and extracellular pBB275 plasmid concentration at 0h or 6 hr in the co-culture.",
    "ncbi_link": "rfp: "
  },
  {
    "caption": "Time-series measurements of (E) the abundance of E. coli MG1655-rfp, (F) the abundance of engineered B. subtilis Unpaired t-test was used to determine if the abundances in the presence and absence of chloramphenicol were statistically different. Stars (*) indicate p-value of 0.0237 and 0.0283 for 4 hr and 8 hr, respectively.",
    "ncbi_link": "rfp: "
  },
  {
    "caption": "Somatic copy number alterations in each individual Kras and Kras/Mad2 non-regressed tumours. 7 K non-regressed and 16 KM non-regressed tumours were sequenced. Focal deletion (DEL, green), Focal amplification (AMP, light green), whole chromosome gain (WCG, dark grey) and loss (WCL, light grey), partial chromosome gain (PCG, dark blue) and loss (PCL, light blue) and gross chromosomal rearrangement (GCR, red).",
    "ncbi_link": "Kras: 16653
Mad2: 56150"
  },
  {
    "caption": "Overlaying of the amplifications in chromosome 6 across multiple regions showing that all amplicons contained the cMet oncogene. Colour of the block corresponds to the segment mean (the degree to which a genome segment is lost (blue) or gained (red).",
    "ncbi_link": "cMet: 17295"
  },
  {
    "caption": "Tumour diameter before and after doxycycline withdrawal in 4 K and 5 KM breast tumours with cMet amplification. 0 indicates when doxycycline was removed. Each colour represents one tumour. Blue and green squares indicate the timeframe between doxycycline withdrawal and the moment in which tumours resumed growth.",
    "ncbi_link": "cMet: 17295"
  },
  {
    "caption": "Representative two-dimensional scatter plots constructed with overlaid dPCR data of the reference (VIC) and cMet (FAM) from one tumour without cMet amplification and one with cMet amplified. Dots represent results of independent PCR reactions in the wells of a digital PCR chip. Reactions in the bottom left corner (yellow) are negative for both targets, while the ones in the top right corner (green) are double positives. Reactions in the top left (blue) and bottom right (red) corners are positive for cMet and the reference targets, respectively.",
    "ncbi_link": "cMet: 17295"
  },
  {
    "caption": "Representative photographs of FISH staining with a probe for Met (red signal) and a probe for a reference gene EML4 (green signals) The upper panel is a negative example for cMet amplification containing 2 red and 2 green dots (white arrows). The lower panel shows an example of a tumour with cMet amplification (several red dots) and 2 green dots (yellow arrow). Scale bar 10 µm.",
    "ncbi_link": "EML4: 78798
cMet: 17295
Met: 17295"
  },
  {
    "caption": "Relative volume of tumours grown in 12 Rag2-/- animals after treatment with Tepotinib or vehicle control (3K and 3KM tumours for each condition). No statistical significance was found by One-way ANOVA. Mean +/- SEM.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "Relative volume of tumours grown in Rag2-/- animals after treatment with Tepotinib or vehicle control. One-way ANOVA, Tukey's multiple comparison. Ns: not significant; ** p<0.024. Mean +/- SEM. A total of 19 Rag2-/- mice injected with cMet expressing tumours were treated with Tepotinib and 14 used as controls. For tumours with no cMet, 13 Rag2-/- mice were treated with Tepotinib and 9 were used as control.",
    "ncbi_link": "cMet: 17295
Rag2: 19374"
  },
  {
    "caption": "Immunostaining of phospho-cMet in the same tumours grown in Rag2-/- mice after treatment with Tepotinib or vehicle control. Scale bar 200 µm.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "Quantification of pH3 in tumours grown in Rag2-/- animals after 5 days treatment with the cMet inhibitor Tepotinib or vehicle control.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "Quantification of caspase 3 in tumours grown in Rag2-/- animals after 5 days treatment with the cMet inhibitor Tepotinib or vehicle control.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": " (B) U2OS stably expressing FLAG-TIP60 or empty vector (vec) were subjected to FLAG- immunoprecipitation from nuclear lysates and analysed by Western blotting ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (C) HEK293T cells were transfected with pcDNA3.1 encoding FLAG-TIP60WT, FLAG- TIP60S90A or empty vector (vec). The samples were subjected to FLAG affinity-purification, dephosphorylated with shrimp alkaline phosphatase (rSAP) and incubated as indicated with CDK9/cyclinT1 in presence of ATP. Phosphorylation of TIP60 was analysed by a phosphoS90-specific TIP60 antibody, and the blot was further probed with antibodies specific for FLAG and CDK9 ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (D) p53-/- hRasG12V MEF were treated with DMSO or 1µM SNS-032 (SNS) for 1h. Nuclear lysates were analysed by Western blotting ",
    "ncbi_link": "hRas: 15461
p53: 22059"
  },
  {
    "caption": " (E) p53-/- hRasG12V MEF were treated with DMSO, 1µM SNS-032 (SNS) or 50µM DRB followed by addition of 100nM Calyculin A as indicated. Nuclear lysates were analysed by Western blotting ",
    "ncbi_link": "hRas: 15461
p53: 22059"
  },
  {
    "caption": " (F) U2OS cells stably expressing FLAG-TIP60WT were transfected with a pool of four different CDK9-targeting siRNAs or a control siRNA targeting Luciferase. Nuclear lysates were analysed by Western blotting ",
    "ncbi_link": "FLAG: 
Luciferase: 
CDK9: 1025
TIP60: 10524"
  },
  {
    "caption": " (A) Localization of TIP60 was analysed employing U2OS cells stably expressing FLAG- TIP60WT, FLAG-TIP60S90A or FLAG-TIP60S86A. Nucleoplasm (nuc.) and chromatin (chr.) fractions were generated and were subjected to Western blot analysis ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (B) The experiment as described in (A) was repeated twice with U2OS cells and twice with Ba/F3 cells and the blots were quantified. Each dot represents the ration of FLAG-TiIP60 to H4 in the chromatin fraction of altogether four individual experiments as shown in (A) ",
    "ncbi_link": "FLAG: 
TiIP60: 10524"
  },
  {
    "caption": " (C) Nuclear extracts of U2OS cells stably expressing FLAG-tagged TIP60WT or TIP60S90A, or FLAG-tagged chromodomain mutants TIP60F50A, TIP60Y47A, TIP60Y44F or the empty vector (vec) were subjected to fractionation into nucleoplasm (nuc.) and chromatin (chr.) fraction. Both fractions were analysed by Western blotting ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (D) Nuclear extracts of U2OS cells stably expressing FLAG-tagged TIP60WT, TIP60S90A, TIP60S90E, TIP60S90D or the empty vector (vec) were subjected to fractionation into nucleoplasm (nuc.) and chromatin (chr.) fraction. Both fractions were analysed by Western blotting",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (E) U2OS cells stably expressing FLAG-tagged TIP60WT, TIP60S90A or empty vector (vec) were treated with 2 µM SNS-032 (SNS) for 3 hours as indicated. The nucleus was fractionated into nucleoplasm and chromatin. Both fractions were analysed by Western blotting",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (A) FLAG- immunoprecipitations were performed from nuclear extracts of U2OS cells stably expressing FLAG-tagged TIP60WT, TIP60S90A, TIP60S86A or empty vector (vec). Immunoprecipitated material and input lysate were subjected to Western blot analysis (B) The experiment as shown in (A) was repeated three times. The graphs and error bars represent mean and standard deviation of these three individual experiments (one-way ANOVA, Fisher"s LSD test, WT vs. S86A p=0,5992, WT vs. S90A p=0,0429, S90A vs. S86A p=0,0176 (*p < 0,05; n.s. not significant, p > 0,05)) ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (C) HEK293 cells were transfected with pcDNA3.1 encoding FLAG-TIP60WT, FLAG-TIP60S90A or empty vector. FLAG-immunoprecipitations were performed from nuclear extracts. Immunoprecipitated material and input lysate were subjected to Western blot analysis ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (D) U2OS cells stably expressing FLAG-TIP60WT or empty vector were treated with 2µM SNS-032 (SNS) for 2 hours as indicated. FLAG-immunoprecipitations were performed from nuclear extracts. This material and input lysate were subjected to Western blot analysis ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (E) U2OS cells stably expressing FLAG-TIP60WT, FLAG-TIP60S90A or empty vector (vec) were subjected to ChIP using anti-FLAG antibody. Immunoprecipitated DNA and input were subjected to quantitative real-time PCR using primers annealing in the myc locus about 50bp upstream (myc+50) or about 500 bp downstream (myc-500) of the transcription start site. Promoter occupancy of FLAG-TIP60WT or FLAG-TIP60S90A was determined as percent input in relation to FLAG -TIP60WT. The graphs and error bars represent mean and standard deviation of three individual experiments (one-way ANOVA, Bonferroni"s multiple comparison test, myc+50 WT vs. S90A p=0,0289, myc-500 WT vs. S90A p=0,0155 (*p < 0,05))",
    "ncbi_link": "FLAG: 
TIP60: 10524
myc: 4609"
  },
  {
    "caption": " (A) U2OS cells stably expressing FLAG-TIP60WT, FLAG-TIP60S90A or empty vector (vec) were treated with 2µM SNS-032 (SNS), 2µM JQ1 (JQ1) or the solvent DMSO (d.) for 2h as indicated. FLAG-immunoprecipitations were performed from nuclear extracts. Immunoprecipitated material and input lysate were subjected to Western blot analysis",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (B) U2OS cells stably expressing FLAG-TIP60WT were treated with 2µM JQ1 (JQ1) for 2h. The nucleus was fractionated into nucleoplasm and chromatin. Both fractions were analysed by Western blotting ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": " (C) HEK293 cells were transiently transfected with pcDNA4 encoding Brd4 or GFP. The nucleus was fractionated into nucleoplasm and chromatin. Both fractions were analysed by Western blotting ",
    "ncbi_link": "GFP: 
Brd4: 23476"
  },
  {
    "caption": " (A) U2OS cells were transfected with a siRNA pool targeting human TIP60 (Dharmacon) or luciferase (Dharmacon). The nuclear lysates were analysed by Western blotting 24h after transfection ",
    "ncbi_link": "luciferase: 
human TIP60: 10524"
  },
  {
    "caption": " (B) U2OS cells stably expressing FLAG-TIP60WT, FLAG-TIP60S90A, FLAG-TIP60S86A or empty vector (vec) were analysed by Western blotting 60 hours after viral transduction ",
    "ncbi_link": "FLAG: 
TIP60: 10524"
  },
  {
    "caption": "(B) Top: Experimental outline of CRISPRa targeting of GBP1 and ASCL1 (control) by transient transfection with plasmids containing dCAS9-SAM. Bottom: HeLa cells were transfected with dCas9-SAM technology with gRNA for indicated genes, either alone or in combination with a 24h exposure to IFNγ. RNA was isolated and GBP1 mRNA expression was measured by RT-qPCR after 48h of transfection and normalized to ACTB expression. Statistical significance was determined using two-way ANOVA. Data are shown as mean. Error bars, SD; n=3 biological replicates.",
    "ncbi_link": "CRISPR: 
ACTB: 60
ASCL1: 429
CAS9: 69900935
Cas9: 69900935
GBP1: 2633"
  },
  {
    "caption": "(C) Top: Experimental outline of CRISPRa targeting of GBP1 and ASCL1 (control) by transient transfection with plasmids containing dCAS9-SAM, followed by induction with IFNγ. Bottom: RNA was isolated, GBP1 mRNA level was determined as indicted in experimental outline in top, by RT-qPCR and normalized to ACTB mRNA level. Statistical significance was determined using Ordinary one-way ANOVA. Data are shown as mean. Error bars, SD; n=3 biological replicates.",
    "ncbi_link": "CRISPR: 
ACTB: 60
ASCL1: 429
CAS9: 69900935
GBP1: 2633"
  },
  {
    "caption": "(B) Stable CRISPR knockouts were generated for indicated genes in HeLa cells. Knockout (KO) cells or their parental controls (WT) were induced with IFNγ for 24 hours or left untreated and prepared for SDS-PAGE and immunoblotting. Blots incubated with GBP5 antibody assess gene expression. α-Tubulin (Tubulin) was used as a loading control. Note that GBP5 and Tubulin blot of parental cells is as in 1C.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "HeLa cells were primed with IFNγ for 24 hours, followed with IFNγ washout. After 48h, naïve and primed cells were induced by IFNγ for 1h and 3h. Cells were harvested at indicated time points and processed for CUT&RUN. Representation of processed data of CUT&RUN for STAT1 (D) and IRF1 (E) occupancy at GBP5 and GBP4 genes. Sequenced reads were mapped to the human genome (hg38), coverage data are displayed as reads per million (RPM) at equal scaling.",
    "ncbi_link": "GBP4: 115361
GBP5: 115362"
  },
  {
    "caption": "(A) Single-cell RNA-seq from HeLa cells for STAT1 Each dot represents STAT1 expression in one cell in naïve (n=91), induction (n=90) and reinduction (n=92). Error bars, SEM.",
    "ncbi_link": "STAT1: 6772"
  },
  {
    "caption": "(C) Blot probing for STAT1 before and after IFNγ induction in STAT1 knockout (STAT1KO), STAT1 rescued (STAT1, constitutive) and parental control (WT), to confirm knockout and rescue status. α-Tubulin (Tubulin) was used as a loading control.",
    "ncbi_link": "STAT1: 6772"
  },
  {
    "caption": "(D) STAT1 rescue cells and their parental control were subjected to IFNγ induction and reinduction regime as outlined in Figure 1A. Cell extracts were processed for western blotting and probed for GBP5 expression before and after induction and reinduction as indicated in Figure 1A. α-Tubulin (Tubulin) was used as a loading control.",
    "ncbi_link": "STAT1: 6772"
  },
  {
    "caption": "(G) Cells constitutively expressing STAT1 (as in B) were primed with IFNγ, followed by IFNγ washout. After 48h, naïve and primed cells were induced by IFNγ for different time points (5, 15, 30, 60, 180 min). Cell extracts were prepared at indicated timepoints and processed for western blotting. Immunoblot of pSTAT1-Y701, and α-Tubulin (Tubulin) as a loading control.",
    "ncbi_link": "STAT1: 6772"
  },
  {
    "caption": "(C) (H) STAT1KO::STAT1-S727E and STAT1KO::STAT1-S727D expressing cells or their parental controls (WT) were subjected to IFNγ induction and reinduction regime as outlined in Figure 1A, RNA was isolated and GBP5 mRNA level was determined by RT-qPCR and normalized to ACTB mRNA level. Statistical significance was determined using Ordinary one-way ANOVA. Data are shown as mean (error bars, SD; n=3 biological replicates).",
    "ncbi_link": "ACTB: 60
GBP5: 115362
STAT1: 6772"
  },
  {
    "caption": "(G) RNA was isolated and GBP5 mRNA level as indicated in (F) was determined by RT-qPCR, normalized to ACTB mRNA level. Statistical significance was determined using two-way ANOVA. Data are shown as mean (error bars, SD; n=3 biological replicates)",
    "ncbi_link": "ACTB: 60
GBP5: 115362"
  },
  {
    "caption": "(A) Wild‐type and rho0 cells harbouring prATG8‐GFP‐ATG8 (upper panels) or prATG8‐GFP (lower panels) were exposed to amino‐acid or nitrogen starvation (‐N) medium supplemented with indicated carbon sources. Cells were analysed at indicated time points by whole cell extraction and western blot analysis using α‐GFP and α‐Cdc11 antibodies. Quantification of ATG8 induction is shown in the lower left panel. Total GFP signals (GFP‐Atg8 and free GFP) were quantified and normalized to Cdc11 signals. Normalized values at 0 h were set as one and relative changes are shown after 6 h starvation. Quantification of autophagic flux is shown in the lower right panel as ratio of free GFP to total GFP signals (GFP‐Atg8 and free GFP) after 6 h starvation. The means and s.d. of four (n=4) independent experiments are indicated.",
    "ncbi_link": "rho: 
ATG8: 852200"
  },
  {
    "caption": "(B) Fluorescence microscopical analysis. Wild‐type, rho0, and Δatg7 cells expressing prATG8‐GFP‐ATG8 were grown as described in (A) and exposed to amino‐acid (left panel, galactose) or nitrogen starvation (right panel, glucose (‐N)) for 6 h. Vacuoles were visualized by over night FM4‐64 (1 μM) staining (red). Arrowhead indicates a punctate GFP‐Atg8 structure. Transmission and fluorescence light microscopy images were superimposed to visualize cellular boundaries. Cellular localization of GFP signal was analysed in at least 150 cells (n⩾150) for each strain and condition. Scale bars represent 1.5 μm.",
    "ncbi_link": "rho: 
atg7: 856576
ATG8: 852200"
  },
  {
    "caption": "Autophagic response in cells with compromised respiratory chain complex III, IV, or V activity during amino‐acid starvation. Wild‐type, rho0, atg7 cells and mutants that are selectively inhibited in the biogenesis of respiratory chain complex III (CIII: cbs1), complex IV (CIV: mss51, pet111, pet122), or the F1Fo‐ATP synthase (complex V; CV: atp10) were exposed to amino‐acidstarvation medium supplemented with acetate (A) or galactose (B). When indicated, wild‐type cells were exposed to antimycin A (AA) or oligomycin (O) during the amino‐acid starvation period. All strains expressed prATG8‐GFP‐ATG8 (upper panels) or prATG8‐GFP (lower panels). Samples were analysed as described in Figure 1A. The means and s.d. of five (n=5) independent experiments are indicated.",
    "ncbi_link": "rho: 
atg7: 856576
ATG8: 852200
atp10: 851109
cbs1: 851491
mss51: 850900
pet111: 855299
pet122: 856897"
  },
  {
    "caption": "(A, B) Wild‐type, rho0, and Δatg7 cells were exposed to amino‐acid starvation medium supplemented with acetate (A) or galactose (B). When indicated, wild‐type cells were exposed to antimycin A (AA) or oligomycin (O) during the amino‐acid starvation period. ATP and protein from total cells (upper panels) or isolated mitochondria (lower panels) were determined at indicated time points.",
    "ncbi_link": "rho: 
atg7: 856576"
  },
  {
    "caption": "(C) Wild‐type and Δatg7 cells were exposed to amino‐acid starvation medium supplemented with acetate or galactose for 3 h. Wild‐type cells were exposed to antimycin A (AA), oligomycin (O), or CCCP (50 μM) during the amino‐acid starvation period when indicated. Cells were treated with the mitochondrial membrane potential‐dependent dye DiOC6(3) and examined by fluorescence microscopy. Average pixel intensities for at least 10 mitochondrial tubules (n=10) in 5 representative cells were determined for each condition. Values for wild‐type mitochondria in the presence of acetate were defined as 100% and relative values were calculated accordingly. The means and s.d. are shown.",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(A) Wild‐type, rho0, Δnpr2, and Δnpr2 rho0 cells expressing prATG8‐GFP‐ATG8 (upper panel) or prATG8‐GFP (lower panel) were exposed to amino‐acid starvation medium supplemented with galactose in the absence or presence of rapamycin. Samples were analysed as described in Figure 1A. The means and s.d. of four (n=4) independent experiments are indicated.",
    "ncbi_link": "rho: 
ATG8: 852200
npr2: 856647"
  },
  {
    "caption": "(B) Wild‐type, rho0, Δnpr2, and Δatg7 cells expressing prNPR1‐NPR1‐HA were exposed to amino‐acid starvation medium supplemented with galactose in the absence (upper panels) or presence (lower panels) of rapamycin. The hyperphosphorylated (Npr1‐P) and dephosphorylated (Npr1) forms of Npr1 are indicated. Cells were analysed at indicated time points by whole cell extraction and western blot analysis using α‐HA and α‐Cdc11 antibodies.",
    "ncbi_link": "rho: 
atg7: 856576
NPR1: 855538
npr2: 856647"
  },
  {
    "caption": "(C) Wild‐type, rho0, Δnpr2, and Δatg7 cells were exposed to amino‐acid starvation medium supplemented with galactose. Additionally, wild‐type cells were treated with rapamycin during starvation (left panel). Phosphorylated (Atg13‐P) and dephosphorylated (Atg13) Atg13 was monitored at indicated time points by whole cell extraction and western blot analysis using α‐Atg13 and α‐Cdc11 antibodies.",
    "ncbi_link": "rho: 
atg7: 856576
npr2: 856647"
  },
  {
    "caption": "(A) PKA‐dependent regulation of the autophagic response under amino‐acid starvation. Wild‐type, rho0, pka, and ras2G19V‐expressing cells harbouring prATG8‐GFP‐ATG8 (upper panels) or prATG8‐GFP (lower panels) were exposed to amino‐acid starvation medium supplemented with galactose. PKA activity in pka was inhibited by addition of 1NM‐PP1 (PP1; 1 μg/ml). Samples were analysed as described in Figure 1A; autophagic flux was determined after 3 and 6 h.",
    "ncbi_link": "rho: 
ATG8: 852200
ras2: 855625
pka: 855898///853275"
  },
  {
    "caption": "(B)In vivo activity of PKA. Wild‐type, rho0, pka, and ras2G19V‐expressing cells harbouring 6xMYC‐cki12−200(S125/130A) (Cki1) were grown in galactose medium. When indicated, wild‐type cells were grown in galactose medium in the presence of antimycin A (AA) or oligomycin (O) for 6 h. PKA‐dependent phosphorylation of Cki1 was analysed by whole cell extraction and western blot analysis using a α‐Myc antibody (upper panels). Ratio of phosphorylated (Cki1‐P) and non‐phosphorylated (Cki1) forms of Cki1 relative to wild‐type cells (wt=1) (lower panels).",
    "ncbi_link": "rho: 
Cki1: 850824
ras2: 855625
pka: 855898///853275"
  },
  {
    "caption": "(C) PKA inhibition restores autophagic flux, but not ATG8 induction in the presence of mitochondrial dysfunction. Wild‐type, rho0, pka, and pka rho0 cells expressing prATG8‐GFP‐ATG8 were treated as described in (A). Samples were analysed as described in Figure 1A. The means and s.d. of four (n=4) independent experiments are indicated in (A-C).",
    "ncbi_link": "rho: 
ATG8: 852200
pka: 855898///853275"
  },
  {
    "caption": "(A)ATG8 induction is independent of the Atg1-Atg13 complex and autophagic flux. Wild‐type, rho0, Δatg1, Δatg7, Δatg9, and Δatg11 cells harbouring prATG8‐GFP‐ATG8 were analysed as described in Figure 1A. The means and s.d. of four (n=4) independent experiments are indicated.",
    "ncbi_link": "rho: 
atg1: 852695
atg11: 856162
atg7: 856576
ATG8: 852200
atg9: 851406"
  },
  {
    "caption": "(B) Atg1 and Atg13 recruitment to the PAS depends on mitochondrial function. Wild‐type and rho0 cells harbouring prATG8‐GFP‐ATG8 and prATG1‐ATG1‐mCherry (upper panels) or prATG13‐ATG13‐mCherry (lower panels) were exposed to amino‐acid starvation medium supplemented with galactose for 3 h. Wild‐type cells were treated with antimycin A (AA 30′) after 2.5 h of starvation for 30 min or with oligomycin (O) for 3 h of starvation. Arrowheads indicate the position of GFP‐Atg8 puncta. Transmission and fluorescence light microscopy images were superimposed to visualize cellular boundaries. Scale bar represents 1.5 μm.",
    "ncbi_link": "rho: 
ATG1: 852695
ATG13: 856315
ATG8: 852200"
  },
  {
    "caption": "(C) Steady‐state levels of Atg1‐ and Atg13‐mCherry during amino‐acid starvation. Wild‐type, rho0, and Δatg7 cells expressing prATG1‐ATG1‐mCherry (upper panels) or prATG13‐ATG13‐mCherry (lower panels) were exposed and treated as described in (B) and analysed by whole cell extraction and western blot analysis using α‐dsRed and α‐Cdc11 antibodies.",
    "ncbi_link": "rho: 
ATG1: 852695
ATG13: 856315
atg7: 856576"
  },
  {
    "caption": "A, B DNA methylation level of NTN1 (A) and DAPK1 (B) 5' regions (Illumina's HumanMethylation450K Array (HM450) from The Cancer Genome Atlas breast cohort) in paired breast tissues (normal: green circles, tumor: red circles), n = 92, Wilcoxon matched-pairs signed rank test, P = 0.004 and P = 0.0008.",
    "ncbi_link": "DAPK1: 1612
NTN1: 9423"
  },
  {
    "caption": "C, D NTN1 (C) and DAPK1 (D) gene expression in paired breast tissues (normal: green bars, tumor: red bars, RNAseq from TCGA breast cohort, n = 112 and 114, respectively.",
    "ncbi_link": "DAPK1: 1612
NTN1: 9423"
  },
  {
    "caption": "E, F Correlation between NTN1 (E) and DAPK1 (F) gene expression and DNA methylation in the breast cancer cohort (TCGA, n = 807). Pearson correlation, P = 6.7.10-5, r = -0.14 for NTN1 (A) and P<10-16, r = -0.32 for DAPK1 (B), respectively.G, H Tumor/Normal DNA methylation ratio of NTN1 (G) and DAPK1 (H) in humanbreasttumors (data extracted from TCGA cohort, paired samples) according to gene expression (downregulated FC ≤ 0.5, down, n = 33, or upregulated FC ≥ 1.3, up, n = 16). P = 3.10-2 and P = 3.10-4 two-sided Mann Whitney test, for NTN1 and DAPK1, respectively.",
    "ncbi_link": "DAPK1: 1612
NTN1: 9423"
  },
  {
    "caption": "A Methyl-Cap-seq read density profiles of the 5' end of DAPK1, UNC5B, and NTN1in MDA-MB-231 (blue) and HMLER (green) cells. Red boxes represent the CpG islands (CGis); light gray boxes the regions analyzed by bisulfite-PCR-sequencing; dark gray boxes the regions analyzed by parallel sequencing of amplicons from bisulfite modified DNA; and black boxes the exons and UTR. Chromosome coordinates of each gene are given (black lines).",
    "ncbi_link": "DAPK1: 1612
NTN1: 9423
UNC5B: 219699"
  },
  {
    "caption": "B, C Gene expression was measured by Q-RT-PCR after 72 h for MDA-MB-231 (B) and HMLER cells (C) treated daily with DAC (10 µM). PBGD expression level was used as an internal control. Data are expressed as mean ± s.e.m. of at least 3 independent experiments. **** P<0.0001, two-tailed unpaired Student's t-test.",
    "ncbi_link": "PBGD: "
  },
  {
    "caption": "D, E Measurement of DNA hypomethylation of the DAPK1 (D) and NTN1 (E) promoters after decitabine treatment of MDA-MB-231 and HMLER cells. Over 1960 sequences were analyzed per group in 2 independent experiments. **** P< 0.0001, two-way ANOVA and post-hoc Tukey-test.",
    "ncbi_link": "DAPK1: 1612
NTN1: 9423"
  },
  {
    "caption": "D Loss of DNA methylation of the NTN1 and DAPK1 promoters in decitabine treated tumors, compared with PBS treated tumors. >1700 sequences were analyzed per group in 2 independent experiments. **** P< 0.0001, two-way ANOVA and post-hoc Tukey-test.",
    "ncbi_link": "DAPK1: 69635
NTN1: 18208"
  },
  {
    "caption": "A Loss of DNA methylation of the NTN1 and DAPK1 promoters in decitabine treated PDX tumors, compared with the control PBS-group. The percentage of mean DNA methylation of the 11 DAPK1-CpGs was 94% (550 amplicons analyzed), while that of the 7 NTN1-CpGs was 64% (213 amplicons analyzed). Two-way ANOVA and post-hoc Tukey-test.",
    "ncbi_link": "DAPK1: 69635
DAPK1: 1612
NTN1: 18208
NTN1: 9423"
  },
  {
    "caption": "B Expression of DAPK1, UNC5B, and NTN1 was measured by Q-RT-PCR in PDX tumors after 7 days of in vivo DAC treatment (0.4 mg/kg). The level of PBGD expression was used as an internal control. Data are expressed as mean ± s.e.m. for at least 3 grafts per group. **** P<0.0001,, two-way ANOVA and post-hoc Tukey-test.",
    "ncbi_link": "PBGD: 
DAPK1: 69635
NTN1: 18208
UNC5B: 107449"
  },
  {
    "caption": "A, D Stably transfected MDA-MB-231 cells bearing a control (A), DAPK1 (B), UNC5B (C), or NTN1 shRNA (D) were injected into the mammary fat pad of immuno-compromised mice. When tumors reached 100-120 mm3, mice were injected subcutaneously with DAC (0.4 mg/kg) or PBS and/or intraperitoneally with net1-mAb (10 mg/kg). Tumor volumes were measured twice a week, n = 8 mice per group. The statistical significance of the differences obtained between DAC-group and DAC + net1-mAb-group for shControl, DAC-group and DAC + net1-mAb-group for shDAPK1 and shUNC5B, and PBS-group and DAC-group for shNTN1, respectively, were determined by two-way ANOVA and a post-hoc Tukey-test. **** P<0.0001, , ns = not significant. Error bars = s.e.m.",
    "ncbi_link": "DAPK1: 1612
DAPK1: 69635
NTN1: 9423
NTN1: 18208
UNC5B: 219699
UNC5B: 107449"
  },
  {
    "caption": "A) Solid phase transfection of nontargeting (scrambled) or PLK1 targeting gRNAs into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 24, 48 and 72 hours and imaged after DNA staining with Hoechst. Green arrowheads indicate examples of prometaphase arrested cells, and the red arrowheads indicate examples of dead cells due to Plk1 downregulation. Phenotypic penetrance is indicated at the top of each panel with standard deviation derived from 2 independent experiments. Scale bar, 20 μm.",
    "ncbi_link": "PLK1: 5347
TP53: 7157"
  },
  {
    "caption": "B) Solid phase transfection of nontargeting (scrambled) or CCNA2 targeting gRNAs into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 72 hours and imaged after DNA staining with Hoechst. C) Quantification of nuclear size measurements from Fig 2B. Data derived from 3 independent experiments. P value (scrambled vs CCNA2) < 2e-16, Kolmogorov-Smirnov test.",
    "ncbi_link": "CCNA2: 890
TP53: 7157"
  },
  {
    "caption": "D) Solid phase transfection of nontargeting (scrambled), GOLGA2 targeting gRNA complexes into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 72 hours, stained with Golga2 antibody (red), and Hoechst (blue) to mark DNA and imaged. Scale bar, 50μm. E) Quantification of experiments in Fig 2D. Data derived from 3 independent experiments. P value (scrambled vs GOLGA2) < 2e-16, Mann-Whitney U test. ",
    "ncbi_link": "GOLGA2: 2801
TP53: 7157"
  },
  {
    "caption": "F) Solid phase transfection of nontargeting (scrambled), MKI67 targeting gRNA complexes into Cas9 expressing RPE-1TP53 -/- cells. Cells were fixed after 72 hours, stained with Ki67 antibody (red), and Hoechst (blue) to mark DNA and imaged. Scale bar, 50μm. G) Quantification of experiments in Fig 2F. Data derived from 3 independent experiments. P value (scrambled vs MKI67) < 2e-16, Mann-Whitney U test. ",
    "ncbi_link": "MKI67: 4288
TP53: 7157"
  },
  {
    "caption": "H) Comparison of phenotypic penetrance with liquid and solid phase transfection. RPE-1, HEK293T, NCI-H358 and NCI-N87 cells were transfected with scrambled or POLR2A targeting gRNAs in in two different cell numbers (2250 or 20000 cells/well). 5 days post transfection cell viability were measured by CellTiter-Glo. Boxplots represent values from at least 3 independent experiments containing 3 technical replicates.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "I) Cell viability measurements after solid phase transfection targeting POLR2A in a panel of cell lines. Cas9 expressing cell lines were transfected with scrambled and POLR2A targeting gRNA and cell viability was assessed after 5 days. The raw values are background subtracted and normalized to the mock controls. Results are from at least 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs POLR2A) < 0.005.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "A) Solid phase transfection of nontargeting (scrambled) or CCNA2 targeting RNP complexes into WT RPE-1TP53 -/- cells. Cells were fixed after 72 hours and imaged after DNA staining with Hoechst. Scale bar, 50μm. B) Quantification of experiments in Fig 3A. Data derived from 2 independent experiments. P value (scrambled vs CCNA2) < 2e-16, Kolmogorov-Smirnov test. ",
    "ncbi_link": "CCNA2: 890
TP53: 7157"
  },
  {
    "caption": "C) Solid phase transfection of nontargeting (scrambled), MKI67 targeting RNP complexes into WT RPE-1TP53 -/- cells. Cells were fixed after 72 hours, stained with Ki67 antibody (red), and Hoechst (blue) to mark DNA and imaged. Scale bar, 50μm. D) Quantification of experiments in Fig 3C. Data derived from 2 independent experiments. P value (scrambled vs MKI67) < 2e-16, Mann-Whitney U test. ",
    "ncbi_link": "MKI67: 4288
TP53: 7157"
  },
  {
    "caption": "E) Four cell lines were transfected with RNP complexes with scrambled or POLR2A targeting gRNA. 5 days post transfection, cell viability in each well was measured. Results are from at least 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs POLR2A) < 0.005.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "A) Viability of NCI-N87 and NCI-H358 cells upon transfection of 45 different gRNAs by solid phase transfection. Cas9 expressing NCI-N87 and NCI-H358 cell were seeded on pre-coated plates. 5 days post transfection, cell viability in each well were measured by CellTiter-Glo. Values were background subtracted, normalized to scrambled controls and plotted against each other. Blue dots represent scrambled controls, whereas the yellow dots represent POLR2A gRNAs. Green dots represent the genes that affect the viability in a cell line dependent manner. Results are representative of 3 independent experiments.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "B, C) Logarithm of the odds (LOD) scores of cancer associated gene KOs in NCI-N87 and NCI-H358 cells derived from screens with gRNAs (B) and RNPs (C). Bottom panels show distribution of positive (POLR2A) and negative (scrambled) controls for each experiment. LOD score of 3 is highlighted with a dashed line, indicating statistical significance.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "A) Solid phase transfection of nontargeting (scrambled) or PLK1 targeting RNP complexes into human primary lung fibroblasts (HLF-1), primary lung adenocarcinoma cells (LAD-1) or RPE-1TP53 -/- cells. 72 hours post transfection cells were stained with Hoechst and imaged. Boxplots represent values from 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs Plk1) < 0.05. In the right panels, representative images for each cell line is shown after RNP transfection targeting PLK1. Arrowheads indicate the cells that are arrested in prometaphase due to Plk1 downregulation. Scale bars indicate 20μm.",
    "ncbi_link": "PLK1: 5347
Plk1: 5347
TP53: 7157"
  },
  {
    "caption": "B) Two human primary lung fibroblasts (HLF) and three primary tumor cell lines derived from patients suffering from either lung squamous carcinoma (LSC) or lung adenocarcinoma (LAD) were transfected with RNP complexes with scrambled or POLR2A targeting gRNA. 5 days post transfection, cell viability in each well was measured. Results are from at least 3 independent experiments containing 3 technical replicates. For all cell lines, P values (scrambled vs POLR2A) < 0.005.",
    "ncbi_link": "POLR2A: 5430"
  },
  {
    "caption": "(C) Transmission electron microscopy (TEM) of crypts of COPS8fl/fl and COPS8ΔIEC mice. The base of the crypt in  COPS8ΔIEC mice is occupied by poorly differentiated  columnar epithelial cells that lack secretory granules, rudimentary electron-dense granules (black arrows), granules in the lumen (blue arrows) and have a contracted endoplasmic reticulum (ER) (white arrows). Scale bar 5μm, data are from seven biological replicates per genotype.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(G-H)   Real-time quantitative reverse transcription Polymerase chain reaction (PCR) (qRT-PCR) analysis of the expression  of genes encoding AMPs in the  ileum (G) and  colon  (H) in COPS8fl/fl and  COPS8ΔIEC mice. Error bars indicate the mean ± SD from three biological replicates. *P<0.05, **P<0.01, ***P<0.001 using Student's t-test.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(A) Real-time quantitative reverse transcription polymerase chain reaction  (PCR) (qRT-PCR) analysis of the differential abundance of selected bacterial taxa in stool  samples of  ileum  and colon of Villin-Cre and COPS8-lox alleles expressing (COPS8fl/fl ) and COPS8  knockout (KO) (COPS8ΔIEC) mice. Error bars indicate the mean ± SD from three biological replicates per genotype. **P<0.01, NS- nonsignificant using Student's t-test. (",
    "ncbi_link": "COPS8: 108679
Cre: 2777477
Villin: 22349"
  },
  {
    "caption": "Mice  were treated by 2% dextran sodium sulfate  (DSS) in drinking water for 7 days. (F) Representative  hematoxylin and eosin (HE)  stained sections of colon  and cecum from COPS8fl/fl and COPS8ΔIEC mice after DSS-indcued colitis (day 9). Scale bar 100μm, representative data from five biological replicates per genotype. (G) Histopathologically scored sections of distal colon; cecum and colon length were analyzed from COPS8fl/fl and COPS8ΔIEC mice after  DSS-indcued colitis (day 7). Data are represented as mean ± SEM from five biological replicates per genotype. **P<0.01 using Student's t-test. (",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "Mice  were treated by 2% dextran sodium sulfate (DSS) in drinking water for 7 days. (H) Cytokine levels (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α)) in the  colon  collected on day 7 in colitis induced COPS8fl/fl and COPS8ΔIEC mice. Data are represented as mean ± SEM from five biological replicates per genotype. *P<0.05, **P<0.01, NS- non-significant using Student's t-test.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "Mice were treated by 2% dextran sodium sulfate (DSS) in drinking water for 7 days. (I) The frequency of CD11b+Ly6C+ and CD11b+Ly6G+ cells in colonic lamina propria  (cLP) of COPS8fl/fl and or COPS8ΔIEC mice  with DSS-induced colitis. The column graph represents percentage of Ly6C+ and Ly6G+ cells, presented as mean ± SEM from three biological replicates per genotype. *P<0.05, NS- non-significant using Student's t-test. (J) Representative  FACS plots and percentage of intracellular staining of  Forkhead box protein P3 (FOXP3), Interferon gamma (IFN-γ) and IL-17A in CD3+CD4+  T cells from  colonic lamina propria  of COPS8fl/fl or COPS8ΔIEC mice with DSS-induced  colitis. The column graph represents percentage of Treg+ and ratio of Th1/Th17 cells, represented as mean ± SEM from three biological replicates per genotype. *P<0.05 using Student's t-test.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(I) Real-time quantitative reverse transcription polymerase chain reaction  (qRT-PCR) analysis of the expression of genes encoding inflammatory cytokines in the ileum. COPS8fl/fl and COPS8ΔIEC mice were either untreated (phosphate buffered saline (PBS)) or treated with the antibiotic cocktail (Abx) for 3 months. Data are mean ± SEM from three biological replicates. **P<0.01, NS- non-significant using one-way ANOVA.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(B) Representative image showing changes in  colon morphology and length following DSS-induced  colitis  with concurrent treatment with MBELNs COPS8fl/fl and COPS8ΔIEC mice. Representative data from seven biological replicates per genotype.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(F)  Expression of anti-microbial peptide (AMPs) in the  colon  of COPS8fl/fl and  COPS8ΔIEC mice  while being treated with  MBELNs by oral administration. Data are mean ± SEM from three biological replicates per group. *P<0.05, **P<0.01, NS- non-significant using one-way ANOVA.",
    "ncbi_link": "COPS8: 108679"
  },
  {
    "caption": "(I-J) Transcriptional expression of  nuclear factor kappa B (NF-κB) (I) and inhibitor of nuclear factor kappa-β kinase (IKK-β) (J) mRNA using Real-time quantitative reverse transcription Polymerase chain reaction (qRT-PCR) in colonic epithelial cells upon treatment with MBELNs  in addition to  DSS. Data are mean ± SEM from three biological replicates per group. **P<0.01, NS- non-significant using one-way ANOVA.",
    "ncbi_link": "IKK-β: 16150
inhibitor of nuclear factor kappa-β kinase: 16150"
  },
  {
    "caption": "Proliferation curves of parental and AGO2KO HeLaS3 cells are plotted (n=6 experimental replicates).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "Colony-forming activity of HeLaS3 and AGO2KO cells was determined by colony-formation assay (n=3 experimental replicates).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "Tumour growth curves of xenografts derived from HeLaS3 or AGO2KO cells are shown as tumour diameter at different time points (n=5 mice for each group).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "HeLaS3 cells were transduced with a lentiviral vector coding for human TERC (HeLaS3_TERC) or for GFP, as a control (HeLaS3_GFP). The relative expression of TERC was measured by RT-qPCR. HPRT1 was used as internal control (n = 3 experimental replicates).",
    "ncbi_link": "GFP: 
HPRT1: 
TERC: 7012"
  },
  {
    "caption": "The relative expression of terc-sRNA was measured in HeLaS3_TERC and HeLaS3_GFP by RT-qPCR. RNU44 was used as internal control (n = 3 experimental replicates).",
    "ncbi_link": "GFP: 
RNU44: 
terc: 7012
TERC: 7012"
  },
  {
    "caption": "Average telomere length was measured from genomic DNA of parental and AGO2KO HeLaS3, by qPCR amplification of telomere repeats (T) and multicopy gene Alu (R), as a reference. The relative telomere length (T/R) was plotted (n=3 experimental replicates)",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "Representative images of metaphase spreads obtained from HeLaS3 and AGO2KO cells stained for telomeric sequences and centromere 2 alphoid DNA.",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "Representative telomere length distributions in parental and AGO2KO HeLaS3. Average telomere length and the standard deviation, as well as the total number of telomeres analyzed, are indicated. Notice the marked shift towards short telomeres in AGO2KO cells compared with the parental HeLa S3 cell line.",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "Telomerase activity was detected by TRAP in parental HeLaS3 and AGO2KO cells. 293T cells were used as a positive control. As negative controls, telomerase was heat- inactivated in cell extracts, in the last lane no cells were added in lysis buffer. Intensity of the telomerase products (6 bp-ladder) was determined by ImageLab Software (Biorad) and normalized with the intensity of the Internal Control (IC) (n=3 experimental replicates).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "AGO2KO cells were transduced with a lentiviral vector coding for FLAG-HA-tagged AGO2 (AGO2KO_FH AGO2) or for GFP as a control (AGO2KO_GFP). Quantification of telomerase activity in AGO2KO_FH AGO2 and AGO2KO_GFP, as assessed by TRAP, was plotted (n=3 experimental replicates).",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
AGO2: 27161"
  },
  {
    "caption": "HeLaS3 cells were transduced with a lentiviral vector coding for FLAG-HA-tagged AGO2 (HeLaS3_FH AGO2) or for GFP as a control (HeLaS3_GFP). Quantification of telomerase activity in HeLaS3_FH AGO2 and HeLaS3_GFP, as assessed by TRAP, was plotted (n=3 experimental replicates).",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
AGO2: 27161"
  },
  {
    "caption": "The relative expression of TERC was measured by RT-qPCR from total RNA of HeLaS3 and AGO2KO cells. HPRT1 was used as internal control (n = 3 experimental replicates). qPCR of 3'-extended TERC transcript in cDNA from HeLaS3 and AGO2KO cells generated using random hexamers. HPRT1 was used for normalization (n=3 experimental replicates). qPCR of TERC transcript in cDNA from HeLaS3 and AGO2KO cells generated using oligo(dT)10 priming. HPRT1 was used for normalization (n=3 experimental replicates).",
    "ncbi_link": "HPRT1: 
AGO2: 27161
TERC: 7012"
  },
  {
    "caption": "Whole cell extract of HeLaS3 and AGO2KO was analyzed by western blot for the presence of TERT protein. GAPDH was used as loading control. Data are representative of 4 independent experiments. TERT protein level was quantified by ImageLab Software (Biorad). GAPDH was use as internal control (n=4 experimental replicates)",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "HeLaS3 and AGO2KO cell extracts (n=3), were immunoprecipitated using an anti-TERT antibody or IgG as mock IP. TERC and HOTAIR (as a negative control) abundance was assessed by RT-qPCR. HPRT1 was used for normalization and enrichment in TERT-RIP as compared to IgG RIP was plotted.",
    "ncbi_link": "AGO2: 27161
HOTAIR: 100124700
TERC: 7012"
  },
  {
    "caption": "AGO2KO_FH AGO2 and AGO2KO_GFP cell extracts (n=3 experimental replicates) were immunoprecipitated using an anti-TERT antibody or IgG as mock IP. TERC and HOTAIR (as a negative control) abundance was assessed by RT-qPCR. HPRT1 was used for normalization and enrichment in TERT-RIP as compared to IgG RIP was plotted.",
    "ncbi_link": "GFP: 
AGO2: 27161
HOTAIR: 100124700
TERC: 7012"
  },
  {
    "caption": "HeLaS3 whole-cell extract was immunoprecipitated using anti- AGO2 antibody or IgG, as mock IP. TERC RNA enrichment in AGO2 RIP as compared to IgG RIP was assessed by RT-qPCR . 7SK RNA was used for normalization (n=4 experimental replicates).",
    "ncbi_link": "TERC: 7012"
  },
  {
    "caption": "RIP assay was performed from HeLaS3_FH AGO2 and HeLaS3_GFP cell extract using anti-HA antibody or IgG, as negative control, followed by TERC detection by RT-qPCR. 7SK RNA was used for normalization (n=3 experimental replicates).",
    "ncbi_link": "GFP: 
AGO2: 27161
TERC: 7012"
  },
  {
    "caption": "HeLaS3 cells were transduced with a lentiviral vector coding for wild-type TERC (HeLaS3_TERCwt), TERC mutated in position 313-340 (HeLaS3_TERC (313-340mut)) or TERC delated in position 12-31 (HeLaS3_TERC (Δ 12-31)). Whole-cell lysates from HeLaS3_TERCwt, HeLaS3_TERC(313-340mut) and HeLaS3_TERC (Δ 12-31) was immunoprecipitated using an anti-AGO2 antibody in order to assessed the impact of TERC mutations on AGO2 binding. For each experiment the enrichment of ectoTERC as compared to 7SK RNA in RIP samples was normalized on the amount of ectoTERC and 7SK RNA in input samples. Association of AGO2 with TERC(313-340mut and TERC (Δ 12-31) was compared to the association with TERCwt (n=3 experimental replicates).",
    "ncbi_link": "TERC: 7012"
  },
  {
    "caption": "HeLaS3 and AGO2KO cells were transfected with a synthetic terc-sRNA or an siRNA with no target in humans (siCtl), as a control. Four days after transfection, telomerase activity in 100- and 50 cell-lysate was assessed by TRAP. Intensity of the telomerase products (6 bp-ladder) was determined by ImageLab Software (Biorad) and normalized with the intensity of the Internal Control (IC), (n=4 experimental replicates)",
    "ncbi_link": "AGO2: 27161
terc: 7012"
  },
  {
    "caption": "D. Control and  biotin-treated  HEK293T cells stably expressing V5-BirA* and V5-BirA*-AURKA were lysed and biotinylated proteins were precipitated  by   streptavidin beads. The initial sample (initial) and captured biotinylated  proteins (pulldown) were run on an SDS gel and  immunoblotted with the fluorescent streptavidin and antibodies against  V5 and vinculin (loading control).",
    "ncbi_link": "V5: 
AURKA: 6790
BirA: 948469"
  },
  {
    "caption": "F. AURKA co-localize with PCM1  at the  peripheral  satellite clusters upon chemical dimerization of satellites with Kif5b motor domain.  U2OS  cells were co-transfected with  GFP-PCM1-FKBP and HA-Kif5b(1-269 a.a.)-FRB and treated with 500 nM rapamycin for 1 hour followed by fixation at 6 hours. Cells that were not treated with rapamycin  were processed in parallel as a control. Fixed cells were  stained  with antibodies against GFP, AURKA and gamma-tubulin. DNA was stained with DAPI. Cell edges are outlined. Scale bar, 10 μm. G. Quantification of  pericentrosomal levels of AURKA and gamma tubulin for F. n>25 cells per experiment. Data represent mean value from two experiments per condition ± SEM (****p < 0.0001; **p < 0.01; Unpaired Student's t-test.). ",
    "ncbi_link": "GFP: 
HA: 
FKBP: 11328///23307///23770///2288///2289
Kif5b: 3799
PCM1: 5108"
  },
  {
    "caption": "A, B. Representative  images and quantification of basal body  levels of (A) AURKA and (B) phospho-AURKA (p-AURKA) in control and  PCM1-depleted cells. RPE1 cells were transfected with control or PCM1 siRNA #1 or siRNA #2 for 48 h. Following 24 h serum  starvation, cells were fixed and stained with the indicated antibodies.  Centrosomal AURKA and p-AURKA fluorescence intensities were measured from maximum projections, and average means of the levels in control cells were normalized to 1. n>500 cells per experiment. Data for (A) AURKA and (B) p-AURKA represent mean value from three experiments per condition ± SEM (****p < 0.0001, Unpaired Student's t-test.) Scale bar, 10 μm",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "D. Cycloheximide chase experiment for quantification of AURKA half-life. Cells were transfected with control or PCM1 siRNA#1 for 48 h, then treated with 200 nM cycloheximide along with serum starvation for indicated time points. AURKA intensities were quantified by immunoblotting for AURKA and vinculin  (loading control) and AURKA levels were normalized to vinculin levels. Data represent mean value from three experiments per condition ± SEM (**p < 0.01, Unpaired Student's t-test)",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "A. Representative  immunofluorescence images of  cilium assembly experiments in control and PCM1-depleted RPE1  cells treated with DMSO  or MLN8237. Cells were transfected with control or PCM1  siRNA#1 for 48 h and treated with  DMSO (vehicle control) or 0.5 μM MLN8237  in  serum starvation medium for 24 h. Cells were fixed and immunostained for the primary cilium with acetylated tubulin antibody (Acet-tub) and the centrosome with gamma-tubulin  antibody. DNA was stained  with DAPI. Scale bar, 10 μm. B. Quantification of  ciliogenesis  efficiency for A. n>100 cells per experiment. Data represent mean value from three experiments per condition ± SEM (***p < 0.001; **p < 0.01; ns, non-significant, Unpaired Student's t-test.). C. Quantification of cilium length for A. n>100 cells per experiment. Data represent mean value from three experiments per condition ± SEM (****p < 0.0001; ns, non-significant, Unpaired Student's t-test.). ",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "D. Representative  immunofluorescence images of cilium assembly experiments in control and PCM1-depleted  RPE1  cells treated with DMSO or tubacin. Cells were transfected with control or  PCM1  siRNA#1 for 48 h and treated with DMSO or 2 μM tubacin in serum starvation medium for 24 h. Cells were fixed and immunostained for the  primary cilium  with Arl13b  and acetylated tubulin antibody (Acet-tub) and the centrosome with gamma-tubulin antibody. DNA was stained with  DAPI. Scale bar, 10 μm E. Quantification of ciliogenesis efficiency for D. n>100 cells per experiment. Data represent mean value from three experiments per condition ± SEM (*p < 0.05; ns, non-significant, Unpaired Student's t-test). ",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "F. Representative immunofluorescence images and quantification of IFT88 levels at the centrosome and primary cilium. RPE1 cells were transfected with control or  PCM1 siRNA#1 for 48 h,  serum starved for 24 h and treated with DMSO or 0.5 μM MLN8237. Cells were fixed and immunostained with antibodies against  IFT88, acetylated tubulin and  gamma tubulin.  DNA was stained with DAPI. Scale bar, 10 μm. G. Quantification of  IFT88 centrosomal intensity and  ciliary concentration for F.  IFT88 fluorescence intensities at the centrosome and axoneme were measured from maximum projections, and average means of the levels in control cells were normalized to 1. Ciliary  concentration was calculated by dividing ciliary fluorescence intensity to the cilium length. n>100 cells per experiment. Data represent mean value from three experiments per condition ± SEM (***p < 0.001; ****p < 0.0001, Unpaired Student's t-test) ",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "H, I. Quantification of cilium  disassembly and centrosomal AURKA levels after  serum stimulation. RPE1 cells were transfected with control or PCM1 siRNA#1 for 48 h, serum starved for 24 h and treated with  DMSO or 0.5 μM MLN8237 in  serum stimulation medium for 2 h and 24 h. Cells were fixed and  immunostained with antibodies against   acetylated tubulin  and gamma tubulin, and percentage of ciliated cells were quantified. x-axis indicates the hours after serum stimulation. (H) n>100 cells per experiment. Data represent mean value from three experiments per condition ± SEM. (I) n>95 cells per experiment. Data represent mean value from three experiments per condition ± SEM (***p < 0.001; ****p < 0.0001, Unpaired Student's t-test).",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "RNA was extracted from young fertile adults fed ad libitum or fasted for 6 h. ddCts (delta delta cycle thresholds) were calculated normalizing to ama-1 and the efficiency of the primer sets as previously described. Means+s.e.m. are depicted. lipl-1 to lipl-5, n = 6 independent experiments. lipl-6 to lipl-8, n = 3independent experiments. Significant t-test derived P-values are indicated. WT, wild type.",
    "ncbi_link": "ama-1: 
lipl-1: 179771
lipl-5: 178563
lipl-6: 179081
lipl-8: 190108"
  },
  {
    "caption": "(b) Acid lipase activity, measured in 1-day adult whole lysates, shows that lipl-1lipl-3 double mutant animals have reduced acidic lipolytic capacity. Mean±s.d. are presented relative to wild type (WT); significant differences are indicated; n = 4 independent experiments.",
    "ncbi_link": "lipl-1: 179771
lipl-3: 178572"
  },
  {
    "caption": "(c) Oil Red O (ORO) staining and fatty acid methyl ester (FAME) analyses of wild-type and lipl-1(tm1954) lipl-3(tm4498) double mutant L3 larvae show that lysosomal lipases regulate cytosolic fat stores (see Fig. 2d for adult measurements). Means±s.e.m. are presented relative to wild type; significant differences are indicated; n = 3 independent experiments. (d) ORO quantification of wild-type and lipl-1(tm1954) lipl-3(tm4498) double mutant young adults fasted for 4 h shows that LIPL-1 and LIPL-3 contribute to fat mobilization following fasting. (Mean percentage ± s.e.m. relative to fed wild type). Wild-type fasted worms show 20% less ORO signal than animals fed ad libitum (P≤0.001), whereas lipl-1(tm1954) lipl-3(tm4498) double mutant worms show 7% reduction in ORO signal (a difference that is not significant to well-fed fat levels at P≤0.01 but it is significant at P≤0.05). n = 3 independent experiments.",
    "ncbi_link": "lipl-1: 179771
LIPL-1: 179771
lipl-3: 178572
LIPL-3: 178572"
  },
  {
    "caption": "(e) Representative transmission electron microscopy images of well-fed and 6 h-fasted wild-type and lipl-1lipl-3 mutant animals (11,500×) show that the lipl mutants have more lipid-droplet stores in ad libitum fed and fasted conditions. Quantification of vesicle number and size is depicted as mean+s.e.m., n = 4 independent experiments.",
    "ncbi_link": "lipl-1: 179771
lipl-3: 178572"
  },
  {
    "caption": "(g) ORO staining and quantification of wild-type and lipl-1(tm1954) lipl-3(tm4498) double mutant young adults treated post-developmentally (from L4) with RNAi against the essential autophagy genes lgg-1 and lgg-2 or vector control show that lipl-1 lipl-3 and the autophagy genes lgg-1 lgg-2 are in the same fat regulatory pathway. (Mean percentage+s.e.m. relative to wild type on vector control is depicted.) n = 4 independent experiments.",
    "ncbi_link": "lgg-1: 174050
lgg-2: 177989
lipl-1: 179771
lipl-3: 178572"
  },
  {
    "caption": "(a) Expression of lipl genes in well-fed mxl-3(ok1947) and mxl-3(tm2580) young adults normalized to same age well-fed wild-type (WT) worms shows that mxl-3 loss of function is sufficient to induce lipl-1 to 3 and lipl-5. Mean ddCts+s.e.m. are depicted. n = 6 independent experiments for lipl-1 to lipl-5, and n = 4 independent experiments for lipl-6 to lipl-8.",
    "ncbi_link": "lipl-1: 179771
lipl-5: 178563
lipl-6: 179081
lipl-8: 190108
mxl-3: 181457"
  },
  {
    "caption": "(b) L4 larvae were fasted and RNA was extracted at the indicated times. Mean ddCts+s.e.m. show that the response mxl-3 orchestrates is transient. Time 0, n = 6 independent experiments; time 3-12 h, n = 4 independent experiments; time 18-24 h, n = 2 independent experiments.",
    "ncbi_link": "mxl-3: 181457"
  },
  {
    "caption": "(d) ChIP-quantitative PCR (ChIP-qPCR) analysis of well-fed and 6 h fasted mixed-stage worms expressing MXL-3::GFP presented as Ct in αGFP immunoprecipitated DNA normalized to input DNA and relative to a mock promoter region (CACTAT site −88 of ama-1 gene) shows that MXL-3 vacates the lipl promoters during early fasting. Three sets of primers surrounding CACGTG target sites found up to 500 bp of the ATG of the lipl-1 and lipl-3 genes were used. A representative experiment is presented; see raw data of two independent experiments in Supplementary Table S9.",
    "ncbi_link": "ama-1: 
lipl-1: 179771
lipl-3: 178572"
  },
  {
    "caption": "(e) Wild-type or lipl-1(tm1954) lipl-3(tm4498) double mutant animals grown on control RNAi plates were transferred as L4 larvae to control or mxl-3 RNAi plates, incubated for 12 h at 20 °C, and processed for total FAMEs; as a reference, an aliquot of wild-type young adults on control RNAi bacteria was fasted for 6 h. FAME quantification (mean percentage of fed wild type ±s.e.m.) shows that acute mxl-3 inactivation, as fasting, reduces fat stores in a lipl-dependent manner. n = 3 independent experiments. NSD, P-value>0.05.",
    "ncbi_link": "lipl-1: 179771
lipl-3: 178572
mxl-3: 181457"
  },
  {
    "caption": "(a) Transcriptional levels of hlh-30 and the mxl-3-dependent lipl genes measured in 5 h fasted wild-type (WT) or hlh-30(tm1978) young-adult worms depicted as mean ddCt+s.e.m. relative to wild-type ad libitum-fed worms show that hlh-30 is induced following fasting and HLH-30 induces lysosomal lipolysis. N = 4 independent experiments for lipl data, n = 2 independent experiments for hlh-30 mRNA. HLH-30 deficiency fully abrogates lipl-2, 3 and 5 (P0.0001), and impairs lipl-1 (P0.01) transcriptional activation following fasting.",
    "ncbi_link": "hlh-30: 177157
HLH-30: 177157
lipl-1: 179771
lipl-2: 185840
mxl-3: 181457"
  },
  {
    "caption": "(b) Animals treated from late L3 stage with RNAi against TOR or vector control were harvested as young adults. Mean+s.e.m. of three independent experiments shows that inhibition of TOR is sufficient to induce hlh-30 transcription.",
    "ncbi_link": "hlh-30: 177157
TOR: 189606///189605"
  },
  {
    "caption": "(c) L3 animals carrying the rescuing construct hlh-30P::HLH-30::mGFP::hlh-30 3′UTR (mGFP, monomeric GFP, and UTR, untranslated region), well fed or fasted for 8 h show that HLH-30 is enriched in intestinal nuclei of fasted worms (exposure time: well fed, 500 ms; fasted, 100 ms).",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(d) ORO staining of wild-type or hlh-30(tm1978) young adults fasted for 8 h reveals that hlh-30 is required for optimal lipid mobilization on fasting. Mean percentages+s.e.m. are shown below relative to well-fed worms treated in parallel, n = 3 independent experiments.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(e) mxl-3 and hlh-30 transcriptional levels in wild-type, hlh-30(tm1978) and mxl-3(ok1947) mutants in the basal and fasted states show that mxl-3 transcription is hlh-30 independent, and hlh-30 transcription is mxl-3 independent. Expression is presented relative to wild-type fed animals as mean ddCt+s.e.m. No significant differences relative to wild type in the same feeding state were observed, n = 3 independent experiments.",
    "ncbi_link": "hlh-30: 177157
mxl-3: 181457"
  },
  {
    "caption": "(g) Transcriptional levels of the mxl-3-dependent lipl genes in wild-type, mxl-3(ok1947), hlh-30(tm1978) or mxl-3(ok1947);hlh-30(tm1978) double mutant young-adult worms show that hlh-30 suppresses the constitutive-induction-of-the-lipl-genes phenotype of mxl-3 mutant animals (mean ddCt+s.e.m. relative to wild-type ad libitum-fed worms). n = 3 independent experiments.",
    "ncbi_link": "hlh-30: 177157
mxl-3: 181457"
  },
  {
    "caption": "(a) LRO (lysosome-related organelle) live Nile red-stained images of hlh-30(tm1978) and wild-type (WT) L3 larvae starved for 60 h show that hlh-30 is required for the expansion of the lysosomal compartment following fasting. Quantification as mean±s.e.m. relative to fasted wild-type worms is also presented; n = 3 independent experiments.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(b) Transcriptional levels of the autophagy genes lgg-1, lgg-2 and atg-16.2 in fasted wild-type and hlh-30(tm1978) young-adult worms show that transcriptional activation of autophagy following fasting is hlh-30 dependent (mean ddCt+s.e.m. relative to wild-type ad libitum-fed worms). n = 3 independent experiments",
    "ncbi_link": "atg-16.2: 174067
hlh-30: 177157
lgg-1: 174050
lgg-2: 177989"
  },
  {
    "caption": "(c) The mean percentage (+ s.d.) of L1 larvae alive after 48 h fasting in minimum media shows that hlh-30 (tm1978) mutant animals are sensitive to starvation. n = 3 independent experiments. For L4 survival see Supplementary Fig. S6g.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(a) Expression analyses of the liver of C57BL/6J 9-week females fasted overnight (ON) for 10 h relative to siblings feeding ad libitum show that LipA (mouse lysosomal acid lipase), Map1lc3a (mammalian lgg-1/lgg-2) and Tfeb (mammalian hlh-30) but not Max (mammalian mxl-3) are transcriptionally linked to nutrients in the mouse liver (median+s.e.m. fold change; ddCt). Levels of expression were normalized to ActB and Cog2 as internal controls; all but Max differences are significant (P0.05), n = 3 independent experiments. Cyp4a14 is a positive control.",
    "ncbi_link": "ActB: 
Cog2: 
Cyp4a14: 13119
hlh-30: 177157
lgg-1: 174050
lgg-2: 177989
LipA: 16889
Map1lc3a: 66734
Max: 17187
mxl-3: 181457
Tfeb: 21425"
  },
  {
    "caption": "(b) Expression analyses of control or hTFEB siRNA treated HepG2 cells incubated in EBSS minimal medium for 2, 4 or 8 h, compared with the expression of control or hTFEB siRNA treated hepatocytes in complete media, show that LAL (human lysosomal acid lipase), MAP1LC3A and TFEB but not MAX are transcriptionally linked to nutrients in human hepatocytes, and that LAL and MAP1LC3A induction under nutrient deprivation are TFEB dependent (median dCt+s.e.m.). Levels of expression were normalized to ACTB as internal control; all butMAX differences are significant (P0.05), n = 3 independent experiments. IGFBP is a positive control. EBSS, Earles's balanced salt solution.",
    "ncbi_link": "ACTB: 
IGFBP: 3484
LAL: 3988
MAP1LC3A: 84557
MAX: 4149
hTFEB: 7942
TFEB: 7942"
  },
  {
    "caption": "(a) Wild-type (WT), mxl-3(ok1947), hlh-30(tm1978) or mxl-3(ok1947);hlh-30(tm1978) double mutant were used in longevity epistasis analyses, revealing that hlh-30 suppresses the mxl-3 extended lifespan phenotype. Animals were incubated at 20°C and transferred every other day until cessation of reproduction. The cumulative survival curve is depicted. Kaplan-Meier statistics, calculated using SSPS 17, are also shown.",
    "ncbi_link": "hlh-30: 177157
mxl-3: 181457"
  },
  {
    "caption": "(b) Live Nile red quantification of wild-type and lipl-1lipl-3 double mutant worms shows that lipl-1 and lipl-3 contribute to the clearance of lipids from the endocytic pathway. Mean+s.e.m. signal intensity is shown as percentage relative to wild type; significant differences are indicated; n = 4 independent experiments.",
    "ncbi_link": "lipl-1: 179771
lipl-3: 178572"
  },
  {
    "caption": "(c,d) Animals overexpressing LIPL-1 or LIPL-3 were incubated at 25 °C and transferred every other day until cessation of reproduction. Data presented as in Fig. 7a show that activated lysosomal lipolysis extends C. elegans lifespan. a Survival presented as mean lifespan (LS) ± s.e.m. b Number of uncensored animals (animals that crawled off the plate, bagged, exploded or became contaminated were censored).",
    "ncbi_link": "LIPL-1: 179771
LIPL-3: 178572"
  },
  {
    "caption": "Snapshots of ChIP-seq signals of Sen1 (this study), RNAP3 (this study) and RNAP2 (data from (Larochelle et al, 2018)) across the U6 snRNA snu6",
    "ncbi_link": "snu6: 
U6 snRNA: "
  },
  {
    "caption": "Snapshots of ChIP-seq signals of Sen1 (this study), RNAP3 (this study) and RNAP2 (data from (Larochelle et al, 2018)) across the srp7 loci.",
    "ncbi_link": "srp7: 5802954"
  },
  {
    "caption": "ChIP-qPCR analysis of the Flag-tagged RNAP3 subunit Rpc37 and Flag-tagged Sen1 across the SPCTRNAARG.10 tRNA locus, whose TATA box was either mutated (TATA-) or not (TATA+). The mutations introduced to disrupt the putative TATA boxes are indicated in red above the graphs. The enrichment values were normalized to SPCTRNATHR.10 (mean ± standard deviation from 4 biological replicates; p-value obtained using the Wilcoxon-Mann Whitney statistical test).",
    "ncbi_link": "SPCTRNAARG.10: 3361068
SPCTRNATHR.10: 3361099"
  },
  {
    "caption": "Strand-specific RT-qPCR was used to quantify the indicated RNAP3 transcripts. Transcript levels were normalized to act1 (mean ± standard deviation from 3 biological replicates).",
    "ncbi_link": "act1: 
RNAP3: "
  },
  {
    "caption": "Snapshots of ChIP-seq signals of the RNAP3 subunits Rpc1 and Rpc2 in the presence or absence of Sen1 across a representative (A) tRNA gene, (B) 5S rRNA gene and (C) srp7. Boxed regions highlight the increased density of reads in the downstream region of genes in the absence of Sen1.",
    "ncbi_link": "Sen1: 2541556
srp7: 5802954"
  },
  {
    "caption": "Average ChIP-seq profile of Rpc1 and Rpc2 across all isolated tRNA and 5S rRNA genes in the presence and absence of Sen1.",
    "ncbi_link": "Sen1: 2541556"
  },
  {
    "caption": "Scanning of Rpc37-3flag occupancy at three different tDNA loci in the absence of Sen1 by ChIP-qPCR (mean ± standard deviation from 6 biological replicates).",
    "ncbi_link": "Sen1: 2541556"
  },
  {
    "caption": "Northern blot analysis of the tRNA SPATRNAPRO.02 using an intron-specific probe (TCTAAACTCAGCATACAAGTGGGG). U5 snRNA was used as a loading control.",
    "ncbi_link": "U5 snRNA: 
SPATRNAPRO.02: 14218195"
  },
  {
    "caption": "ChIP-qPCR analysis of Rpc37 around SPCTRNAARG.10 gene in the strong terminator mutant (mean ± standard deviation from 4 biological replicates).",
    "ncbi_link": "SPCTRNAARG.10: 3361068"
  },
  {
    "caption": "Strand specific RT-qPCR was used to quantify read-through transcripts at SPCTRNAARG.10 (arg10) and SPCTRNASER.09 (ser09) in the strong terminator mutant (mean ± standard deviation from 4 biological replicates; p-value obtained using the Wilcoxon-Mann Whitney statistical test).",
    "ncbi_link": "arg10: 3361068
SPCTRNAARG.10: 3361068
SPCTRNASER.09: 3361067
ser09: 3361067"
  },
  {
    "caption": " (D-E) RT-qPCR analysis of the mRNA levels of MyoD (D 24h after treatment relative to the NT control. Data information: All quantifications are of three independent experiments (n = 3) and error bars represent standard error of the mean (SEM). Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from NT controls; ††, p < 0.01 from IFNγ/TNFα treated controls ",
    "ncbi_link": "MyoD: 17240"
  },
  {
    "caption": " (D-E) RT-qPCR analysis of the mRNA levels o myogenin (E) 24h after treatment relative to the NT control. Data information: All quantifications are of three independent experiments (n = 3) and error bars represent standard error of the mean (SEM). Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from NT controls; ††, p < 0.01 from IFNγ/TNFα treated controls ",
    "ncbi_link": "myogenin: 17928"
  },
  {
    "caption": " (F) RT-qPCR analysis of iNOS mRNA levels relative to the IFNγ/TNFα control 24h after treatment Data information: All quantifications are of three independent experiments (n = 3) and error bars represent the SEM For panels E through G, p-values were calculated using the Student"s t-test. *, p < 0.05; **, p < 0.01 from DMSO controls; ††, p < 0.01 from IFNγ/TNFα treated controls",
    "ncbi_link": "iNOS: 106736473"
  },
  {
    "caption": " (D-E) RT-qPCR analysis of Atrogin-1/MAFbx (D mRNA expression from the tibialis anterior of three mice per cohort (n = 3). Data information: Error bars represent the SEM. Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from saline controls; †, p < 0.05; ††, p < 0.01 from C26 controls ",
    "ncbi_link": "Atrogin-1: 67731
MAFbx: 67731"
  },
  {
    "caption": " (D-E) RT-qPCR analysis o MuRF1 (E) mRNA expression from the tibialis anterior of three mice per cohort (n = 3). Data information: Error bars represent the SEM. Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from saline controls; †, p < 0.05; ††, p < 0.01 from C26 controls ",
    "ncbi_link": "MuRF1: 433766"
  },
  {
    "caption": " (B-C) RT-qPCR analysis of Atrogin-1/MAFbx (B mRNA expression from the tibialis anterior of four mice per cohort (n = 4). Data information: Error bars represent the SEM. Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from PF controls ",
    "ncbi_link": "Atrogin-1: 67731
MAFbx: 67731"
  },
  {
    "caption": " (B-C) RT-qPCR analysis o MuRF1 (C) mRNA expression from the tibialis anterior of four mice per cohort (n = 4). Data information: Error bars represent the SEM. Significance between means was first determined using ANOVA. Significance p-values were calculated using Fisher"s LSD. *, p < 0.05; **, p < 0.01 from PF controls ",
    "ncbi_link": "MuRF1: 433766"
  },
  {
    "caption": "Retrotransposon transcription in WT (Hu303), fft2Δ (Hu1955), fft3Δ (Hu1867), and fft2Δfft3Δ (Hu2000). A) Transcription in fft2Δ relative to WT over chromosome 1. The top and bottom panels represent fold change in tiling array signal from the forward and reverse strands, respectively. Coordinates are shown in the middle panel; genes more than 2-fold upregulated are marked: Tf2 retrotransposons (black); antisense to Tf2 elements (gray); coding genes (green); noncoding RNAs (blue)",
    "ncbi_link": "Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "Retrotransposon transcription in WT (Hu303), fft2Δ (Hu1955), fft3Δ (Hu1867), and fft2Δfft3Δ (Hu2000). B) Northern blot for the Tf2 ORF; rRNA staining of the same membrane by methylene blue is shown below. Two different exposures of the molecular size marker are shown (left).",
    "ncbi_link": "Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "Retrotransposon transcription in WT (Hu303), fft2Δ(Hu1955), fft3Δ (Hu1867), and fft2Δfft3Δ (Hu2000). C) qPCR scheme. Amplicon 1 spans the end of the LTR and into the ORF. Amplicon 2 does not include the LTR but covers the translation start site. Amplicon 3 is entirely within the ORF. D) Bar graph representing RNA levels for the amplicons depicted in (C), relative to a control locus (SPAC1F8.07c) and to WT levels, as measured by qPCR. Error bars represent standard deviation of duplicate reverse transcriptions of biological triplicates.",
    "ncbi_link": "SPAC1F8.07c: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "Retrotransposon transcription in WT (Hu303), fft2Δ (Hu1955), fft3Δ (Hu1867), and fft2Δfft3Δ (Hu2000). E) 5'RACE products run on a 1.5% agarose gel.",
    "ncbi_link": "fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "Top panel: Y-axis shows the CAGE signal intensity (tag-per-million normalized number of mapped CAGE tags on plus strand). X axis shows LTR and 5' of Tf2 ORF. Three biological replicates are shown for each strain: fft2Δfft3 and WT. Bottom: LTR and tf2 ORF are colored: U3 (green), R (red), U5 (blue), self primer and primer binding sequence (PBS; gray), beginning of ORF (gray striped). TSS of all Tf2 transcripts from (Rhind et al, 2011) are shown as gray dots above the sequence elements. The black square indicates the 5' end of the Tf2 mRNA in WT and the green square indicates the 5' end in fft2Δ fft3Δ detected by 5'RACE.",
    "ncbi_link": "Tf2: 
tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "A) Fft2 and Fft3 are both enriched at LTRs, while Fft2 is also enriched at the tf2 coding region. Fft2 LTR enrichment increases in fft3Δ cells, while Fft3 LTR enrichment decreases slightly in fft2Δ cells. Top: Fft2 -myc enrichment in WT (solid line) and in fft3Δ (dashed line). Bottom: Fft3 -myc enrichment in WT (solid line) and in fft2Δ (dashed line). ChIP-chip signal is normalized against no-epitope control arrays.",
    "ncbi_link": "tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "B) Nucleosome occupancy over the LTR U3 is significantly reduced (average reduction ~50%; average p-values at each position <0.001, Poisson test) in fft2Δ fft3Δ cells. MNase-seq data aligned at the start of tf25'LTRs is shown for WT (black line), and fft2Δ fft3Δ (dark gray line). Light gray line indicates significance of difference between WT and mutant signals: amplitude reflects significance (p-value) and sign reflects the sign of occupancy change in mutant vs. WT cells. Error bars show standard deviation of nucleosome occupancy averaged over 13 tf2 elements. LTR and tf2ORF are colored: U3 (green), R (red), U5 (blue), self primer and primer binding sequence (PBS; gray), beginning of ORF (gray striped). TSS of all tf2 transcripts from (Rhind et al, 2011) are shown as gray dots above the sequence elements, while the green dot indicates the TSS in fft2Δ fft3Δ.",
    "ncbi_link": "tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "A) Mean nucleosome occupancy over solo LTRs (n=236) and tf2-associated LTRs (n=25), in WT and in fft2Δ fft3Δ.",
    "ncbi_link": "tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "B) Mean ratio of expression (fft2Δ fft3Δ /WT) for each of the following categories: non-coding with LTR (n=69) / without LTR (n=1665) (p=0.008); protein coding with LTR (n=246) / without LTR (n=4887) (p<0.001); Tf2s (n=13). A and B) Data shown as box plots, significance of difference between categories was assessed by Wilcoxon-Mann-Whitney test (** p<0.001).",
    "ncbi_link": "Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "A) Heat and oxidative stress cause a Tf2 TSS shift in WT cells, resulting in the production of reverse transcription competent Tf2 transcripts. Transcription fold change as in Figure 1D, but relative to act1 transcription and to transcription in the same culture immediately prior to stress, as measured by qPCR. Error bars represent standard deviation of reverse transcriptions of biological duplicates.",
    "ncbi_link": "act1: 
Tf2: "
  },
  {
    "caption": "B) Heat shock-associated TSS shift is accompanied by a reduction in LTR nucleosome occupancy. The degree of nucleosome loss is greater in WT cells than in fft2Δ fft3Δ cells, where nucleosome occupancy is already very low (Fig 2B, Fig S3). LTR nucleosome occupancy shown relative to occupancy of the Tf2 ORF +1 nucleosome, measured by MNase-qPCR.",
    "ncbi_link": "Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "C) Exposure to stress conditions does not increase Tf2 transcript levels further in fft2Δ fft3Δ cells. Transcription fold change as in Figure 1D, but relative to act1 transcription and to transcription in the same culture immediately prior to stress, as measured by qPCR. Error bars represent standard deviation of reverse transcriptions of biological duplicates",
    "ncbi_link": "act1: 
Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "B) Bar graph representing RNA levels as in Fig. 1D, relative to a control locus (act1) and to WT levels, as measured by qPCR. Error bars represent standard deviation of nucleosome occupancy of biological duplicates.",
    "ncbi_link": "act1: "
  },
  {
    "caption": "A) Fluorescencein situ hybridization with a probe against tf2 elements (green), and DAPI staining (blue) in WT and fft2Δ fft3Δ cells. B) The number of tf2 element signal clusters is significantly elevated (p=9.8x10-18, χ2-test) in fft2Δ fft3Δ cells, indicating a loss of retrotransposon clustering. Tf2 clustering was counted in wt cells (n=663), fft2∆ (n=556), fft3∆ (n=493), fft2∆ fft3∆ (n=636). Significance of difference between strains was assessed by Chi-square test.",
    "ncbi_link": "tf2: 
Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "A) Pictures of YES plates with G418 showing growth of G418 resistant subclones in fft3D (PP3) and fft2Dfft3D (PP4) mutant strains with new integrations of Tf2-12-neoAI. After 3 days at 32o C.",
    "ncbi_link": "Tf2: 
fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "C) Southern blot probed for neoA fft3D (PP3) and fft2Dfft3D mutant strains (PP4) and derived G418 resistant subclones.",
    "ncbi_link": "fft2: 2539045
fft3: 2541531"
  },
  {
    "caption": "The Dyf phenotype of the ts-che-3 mutant was confirmed, with animals grown at the permissive temperature (15ºC) showing the ability to uptake dye, while those raised at the restrictive temperature (25ºC) are Dyf. Scale bar, 20 µm",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "Using the homodimeric kinesin OSM-3 as a marker for IFT, proper localisation is seen in the ts-che-3 mutant at the permissive temperature, with the strongest signal at the basal body (bb). At the restrictive temperature, most of the OSM-3 signal is found within the axoneme of the short, bulbous cilia. Scale bar is 4 µm",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "The ts-che-3 mutant shows normal osmotic avoidance at permissive temperature but not at the restrictive temperature, indicating defective chemosensation. The osm-9 mutant is included as a positive control. n = 50 animals; error bars are standard error",
    "ncbi_link": "che-3: 172593
osm-9: 177117"
  },
  {
    "caption": "Three TZ markers (NPHP-4, CEP-290 and MKS-6) are shown at both the permissive (15ºC) and restrictive (25ºC) temperatures in the ts-che-3 mutant. At the permissive temperature, all three markers localise to the TZ, while at the restrictive temperature exhibit ectopic localisation (leakage) distally into the ciliary axoneme. While NPHP-4 and MKS-6 show significant accumulations, CEP-290 is grossly normal. At the permissive temperature, both IFT co-markers (CHE-13 and XBX-1) display strong localisation to the basal body (bb) and along the axoneme. At the restrictive temperature, the IFT markers show accumulation in the axoneme. Accumulations emphasized using asterisks",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "To determine if ciliary compartmentalisation could be restored, young ts-che-3 mutant adults were transferred to the permissive temperature after being raised at the restrictive temperature. The TZ proteins reassembled at the TZ, with loss of the ectopic accumulations, and IFT protein localisation was also restored-strongest at the basal body, similar to animals grown at the permissive temperature. (c) After 24 hours at the restrictive temperature, TZ proteins appear to begin to accumulate distally within the axoneme in ts-che-3 mutants. This is seen, in small amounts, for NPHP-4 and CEP-290 but with stronger ectopic localisation for MKS-6. The IFT proteins CHE-13 and XBX-1 also show accumulations in the axoneme after 24 hours at the restrictive temperature. Data information: For (A), (B), and (C), fluorescence quantification is shown for each marker at the indicated temperature in the heat maps on the right. Each point in the plot represents one pixel along the centre of the basal body (BB), transition zone (TZ) and middle segment (MS) regions. Dotted areas (three pixels) in the MS were used to quantify ectopic localisation (TZ markers) or accumulation (IFT markers) for statistical analyses. n = 10 cilia (4-7 animals), Kruskal-Wallis test, *P<0.05, **P<0.01. tz, transition zone; bb, basal body; scale bars are 4 µm",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "In the ts-che-3 mutant grown at the permissive temperature (15ºC), both RPI-2/RP2 and TRAM-1/TRAM1 are localised to the PCMC, just proximal to the ciliary axoneme. At the restrictive temperature, TRAM-1 shows leakage into the axoneme with its strongest localisation at the PCMC. Intriguingly, RPI-2 now displays strong localisation to the axoneme, indicating that in the absence of IFT, RPI-2 may be targeted into the cilium. When ts-che-3 mutant animals grown at the restrictive temperature (25ºC) are shifted at young adult to the permissive (15ºC) for 24 hours, both TRAM-1 and RPI-2 exhibit restoration of their PCMC localisation. Consistent with other TZ markers, both MKS-2 and MKSR-1 show ectopic localisation in the axoneme when grown at the restrictive temperature compared to the permissive temperature. Also consistent with what was observed for other markers, after 24 hours at the permissive temperature, animals grown at the restrictive temperature show loss of the ectopic localisation. Fluorescence quantification is shown for each marker at the indicated temperature in the heat maps on the right. Each point in the plot represents one pixel along the centre of the basal body (BB), transition zone (TZ) and middle segment (MS) regions. Dotted areas (three pixels) in the MS were used to quantify ectopic localisation (MKS-2 and MKSR-1) or accumulation (RPI-2 and TRAM-1) for statistical analyses. n = 10 cilia (4-6 animals), Kruskal-Wallis test, *P<0.05, **P<0.01; scale bars are 4 µm",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "Loss of CHE-3 function results in short, bulbous cilia containing electron dense accumulations and abnormal membrane-microtubule connections. Shown are transmission electron micrograph (TEM) cross sections of an amphid channel cilium in wild-type and che-3(e1124) null mutant animals. Representative images of wild-type cilia show intact middle segment (containing doublet microtubules) and transition zone (with Y-shaped links) (left top and bottom panels) regions. Representative images of che-3(e1124) cilia reveal apparently intact transition zones, with visible Y-link structures, but enlarged ciliary ends filled with electron-dense accumulations, which often appear vesicular. The bulbous structures reveal doublet microtubules associated with the membrane, and occasionally ectopic microtubule-to-membrane connections, which sometimes appear similar to transition zone Y-links in the region just distal to the seemingly \"normal\" TZ structure. Schematics show longitudinal (left images) and cross section (right images) representations of wild-type and che-3(e1124) cilia. tz, transition zone; pcmc, periciliary membrane compartment; scale bars are as indicated in (nm) for",
    "ncbi_link": "CHE-3: 172593
che-3: 172593"
  },
  {
    "caption": "Using the IFT marker BBS-7, cilia lengths were measured for wild-type and the ts-che-3 mutant animals raised at the permissive (15ºC) and shifted to the restrictive temperature (25ºC) for three time points. After 12 hours some accumulations (indicated by asterisks in the fluorescence images) are observed within the cilia but there is not a significant reduction in cilium length. After 18 and 24 hours, significant reduction in ciliary length is observed and large accumulations of BBS-7 is seen within short bulbous cilia, similar to what is observed in ts-che-3 animals raised at the restrictive temperature. n = 30-34 cilia, one per animal; Kruskal-Wallis test, **P<0.01; error bars are mean absolute deviation; scale bars are 4 µm",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "IFT velocities were measured for wild-type or ts-che-3 mutant animals (grown at permissive temperature) and imaged at the permissive temperature, restrictive temperature or after 3 hours at the restrictive temperature. Compared to wild-type, anterograde velocities in the ts-che-3 dynein mutant are similar, while IFT retrograde rates are highly reduced for both the middle and distal ciliary segments. Interestingly, the ts-che-3 IFT dynein mutant appears to not only have slow retrograde IFT trains, but the trains also appear much larger and less frequent. Initially upon the temperature shift (<15min) IFT rates are much faster for both wild-type and ts-che-3 dynein mutant, although retrograde remains much slower in the mutant. After 3 hours at the restrictive temperature, IFT velocities are intermediate between the rates seen at 15ºC and those observed at the initial shift to 25ºC",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "To assess the effects of IFT restoration on TZ assembly, ts-che-3 mutant animals were shifted from the restrictive to the permissive temperature at different time points during their development (days 1, 4 and 8 of adulthood). The TZ markers MKS-6 (a) and NPHP-4 (b) show strong ectopic ciliary accumulations when raised at the restrictive temperature until day 1 of adulthood. After a shift to the permissive temperature for 24 hours, day 2 adults show \"repaired\" TZ protein localisation resembling that of wild-type animals. For both markers, Day 4 adults (maintained at the restrictive temperature) show less ectopic TZ protein localisation than Day 1 adults. The correction of ectopic localisation following shift to the permissive temperature for 24 hours was reduced in day 4 (to day 5) of adulthood compared to that observed in day 1 (to day 2) adults. For MKS-6, but not NPHP-4, day 8 adults (maintained at the restrictive temperature) also display less ectopic accumulation than day 1 adults. The correction of ectopic TZ protein localisation in animals shifted to the permissive temperature after 8 days of adulthood is also much smaller in magnitude for both markers, indicating that this repair is most effective in day 1 adults. In summary, as the adults age, ectopic TZ protein localisation is reduced, while the ability to correct this phenotype by restoring IFT function al",
    "ncbi_link": "che-3: 172593"
  },
  {
    "caption": "A EN qRT-PCR of murine liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC), hepatocytes (Hep), and HSC (n = 3 per cell type).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "B EN qRT-PCR of human hepatocytes (n = 1) and HSC cell line LX-2 (n = 3).",
    "ncbi_link": "EN: 57124"
  },
  {
    "caption": "D EN qRT-PCR of normal liver (NL) and fibrotic liver (FL,n = 8 each), and active or inactive cirrhotic liver (CL+/−, n = 10/ n = 2).",
    "ncbi_link": "EN: 57124"
  },
  {
    "caption": "O EN/αSMA mRNA ratio in normal liver, fibrotic liver, and active cirrhotic liver.",
    "ncbi_link": "αSMA: 59
EN: 57124"
  },
  {
    "caption": "P Collagen 1a (Col1a) expression in normal, fibrotic, and active cirrhotic liver determined by qRT-PCR.",
    "ncbi_link": "Col1a: 1278///1277
Collagen 1a: 1278///1277"
  },
  {
    "caption": "A, B qRT-PCR for EN (A) and αSMA (B) of liver lysates from single high-dose CCl4- or oil-treated wild-type (WT) mice (n = 2 per time point).",
    "ncbi_link": "αSMA: 11475
EN: 70445"
  },
  {
    "caption": "C Early activated and long-term-activated HSC isolated by differential density gradient centrifugation (8.26% versus 11.5% density layer). qRT-PCR for EN from early activated (8.26%) and long-term-activated HSC (11.5%) from 4-week CCL4-treated mice and vehicle control mice (n = 3-4 per data point).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "D EN expression in liver lysates from 2-, 4-, and 6-week CCl4-treated mice (n = 5-8) and vehicle control mice (n = 3) determined by qRT-PCR.",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "E-G METAVIR score of 2-, 4-, and 6-week CCl4-treated mice (F-G) Col1a and F4/80 immunofluorescence of 6-week CCl4-treated and vehicle control WT (F) and ENKO (G) mice.H Mean Col1a+ area per high power field (HPF) shown as percentage of the total area (n = 5-8).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "I Western blot analysis for collagen 1a (Col1a), platelet-derived growth factor receptor beta (PDGFRβ) and β-actin of total liver protein lysates from 6-week CCl4-treated or control vehicle WT and ENKO mice (n = 3-5).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "J-L Double immunofluorescence of 6-week CCl4-treated and vehicle control WT (J) and ENKO (K) mice for desmin and αSMA (L) shown as percentage of the total area (n = 5-8).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "M Serum liver enzymes (GPT/ALT and GOT/AST) from 2-, 4-, and 6-week CCl4-treated WT and ENKO mice (n = 5-8).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "N qRT-PCR of endosialin (EN), αSMA, and collagen 1a1/6a1 from lentiviral-mediated endosialin knockdown (shEN) and control-transfected (CTL) human hepatic stellate cells (LX-2).",
    "ncbi_link": "αSMA: 59
EN: 57124
endosialin: 57124
collagen 1a1: 1277"
  },
  {
    "caption": "O Lentiviral-mediated endosialin knockdown (shEN) and control (CTL) in LX-2 cells (n = 3). Magnification 10×.",
    "ncbi_link": "EN: 57124
endosialin: 57124"
  },
  {
    "caption": "A Representative images of Ki-67 immunohistochemistry after 2, 4, and 6 weeks of CCl4 treatment of WT and ENKO mice (n = 5-8 mice per group and time point). Scale bars: 75 μm.B Quantitation of Ki67+ hepatocytes/HPF after 2, 4, and 6 weeks of CCl4 treatment.",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "C Time course of EN expression after partial hepatectomy (2/3 PHx) determined by qRT-PCR of total liver lysates (n = 5/time point, sham: n = 3).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "D Representative images of Ki-67immunohistochemistry 2 days after 2/3 PHx of WT and ENKOmice (n = 5-9 mice per group and time point).E Quantitation of Ki-67+hepatocytes/HPF determined 1, 2, 4, and 8 days after 2/3 PHx.F Number of mitotic figures 2 days after 2/3 PHx of WT and ENKOmice (n = 5-9 mice per group and time point).",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "G qRT-PCR analysis of total liver lysates 1 day after PHx for IGF2.",
    "ncbi_link": "IGF2: 16002"
  },
  {
    "caption": "J, K qRT-PCR of IGF2 in isolated liver sinusoidal endothelial cells (LSEC)(J) or hepatocytes (HEP)(K) 1 day after PHx.",
    "ncbi_link": "IGF2: 16002"
  },
  {
    "caption": "L EdU-positive hepatocytes (in %) after 24-h stimulation with conditioned medium (CM) from either WT or ENKO HSC (3, 5, or 7 days of activation). HGF (40 ng/ml) and TGF-β (10 ng/ml) serve as positive or negative control, respectively.",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "M EdU-positive WT and ENKO hepatocytes (in %) after stimulation with IGF2 (100 ng/ml). HGF (40 or 10 ng/ml) and TGF-β (10 ng/ml) serve as positive or negative control, respectively.",
    "ncbi_link": "EN: 70445"
  },
  {
    "caption": "Immunoblot analysis of presenilin expression and endoproteolysis in cell lysates of untransfected HEK293/sw cells endogenously expressing presenilin and single cell clones overexpressing PS1 WT or the indicated PS1 mutants.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "ELISA analysis of Aβ species in conditioned media of HEK293/sw cells overexpressing WT or mutant PS1 treated with RO7019009 or vehicle (DMSO) showing the secretion of Aβ38 (A), Aβ43 (B) and Aβ42 (C) compared to total Aβ (Aβ38 + Aβ40 + Aβ42 + Aβ43) (n = 5 biological replicates). Note that in some experiments Aβ38 generation was below the detection limit for some mutants. Data are presented as mean ± SD.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Mass spectrometry analysis of Aβ species immunoprecipitated from conditioned media of HEK293/sw cells overexpressing WT or mutant PS1 treated with 500 nM RO7019009 or vehicle (DMSO).",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Characterization of OAS1-3 expression in parental and OAS knockout PC3 cells, obtained using CRISPR-Cas9 technology. Left: Western blot (WB) analyses of the expression of OAS1, 2, and 3 in clones of OAS single-, double- or triple-knockout PC3 cells (KO, DKO, TKO), treated with IFNβ (500 IU/ml) for 24 h, to increase OAS expression. sgOAS1-3 - single guide RNA for OAS1-3. β-actin is shown as a loading control. Right: analysis of the expression of OAS1, 2, and 3 in PC3 DKO cells with increased expression of the remaining OAS, without IFNβ treatment. OAS1 expression in DKO2/3 cells was measured by qRT-PCR due to insufficient sensitivity of anti-OAS1 (see Fig EV1A), OAS2 and 3 expression was detected by WB. The gene expression data are presented as mean + SD of triplicates.**, p<0.001 in Student's t-test.",
    "ncbi_link": "Cas9: 
CRISPR: 
OAS1: 4938"
  },
  {
    "caption": "Characterization of OAS1-3 expression in parental and OAS knockout HME cells, obtained using CRISPR-Cas9 technology. Left: WB analyses of the expression of OAS1, 2, and 3 in selected clones of HME cells in which OAS1-3 were knocked out, to produce OAS single-, double- or triple-knockout cells (KO, DKO, TKO), treated with 100 IU/ml IFNβ for 24 h to increase the levels of OAS expression. sgOAS1-3 - single guide RNA for OAS1-3. β-actin is shown as a loading control. Right: The expression of OAS1, 2, and 3 in HME DKO cells with increased expression of the remaining OAS, without IFNβ treatment. The expression of OAS2 or 3 was determined by WB analysis (asterisk, non-specific band). OAS1 expression in DKO2/3 cells was measured by qRT-PCR due to insufficient sensitivity of anti-OAS1. The gene expression data are presented as mean + SD of triplicates. **, p<0.001 in Student's t-test.",
    "ncbi_link": "Cas9: 
CRISPR: 
OAS1: 4938"
  },
  {
    "caption": "OAS expression was assessed by WB with anti OAS1-3 in HME cells expressing ectopic OAS1-3 (OAS2hi, OAS3hi, OAS1hi) cells without IFNβ treatment or control HME cells (vec) treated with the indicated concentrations of IFNβ for 2 days (to compare the levels of induced and ectopically expressed OASs). β-actin and Ponceau stain are shown as loading controls (# - transfer artifact); ns, non-specific band.",
    "ncbi_link": "OAS1: 4938
OAS2: 4939
OAS3: 4940"
  },
  {
    "caption": "Analysis of the percentages of dead HME DKO cells and HME DKO cells with high expression of the remaining OAS, treated with 500 μM H2O2, and KO1-3 and OAS1-3hi cells treated with 750 μM H2O2. Data were obtained and presented as in (A). Means of triplicates ± SD. ***, p<0.001; **, p<0.01; ns, no significance in two-way ANOVA. Representative data, which were reproduced more than 3 times, are shown.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "Survival of HME cells, measured by the MTT cell survival assay. Left: control (vec) and KO1-3 cells were treated with 250, 500 or 750 μM of H2O2 and analyzed after 24 h; Right: control, OAS1hi and OAS KO were treated with 500 μM of H2O2 and analyzed after 72 h . The data are presented as mean + SD of triplicates. ***, p<0.001; **, p<0.01; *, p<0.05 in Student's t-test.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "Immunostaining of PAR-2-5A synthesized in vitro. Reaction mixtures were resolved by electrophoresis in a polyacrylamide-8 M urea denaturing gel, transferred to a charged nylon membrane, and probed with mouse anti-PAR 10H (left panel) or rabbit anti-2-5A after stripping (right panel). XC: Xylene Cyanol (apparent size 150 nucleotides), BPB: Bromophenol Blue (apparent size 35 nucleotides). Lane 1, purified PARP1 alone; lane 2, PAR reaction: PARP1, activated DNA, NAD+, and histone; lane 3, 2-5A reaction: OAS1, pIC, ATP; lane 4, 2-5A and PAR reactions: OAS1, pIC, ATP and PARP1, activated DNA, NAD, histone. After incubation at 37oC for 60 min, the proteins were removed by digestion with proteinase K.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "Western analysis of PARP1 auto-modified with PAR in vitro in the absence or presence of OAS1. Reaction mixtures were resolved by SDS-PAGE, transferred to a charged nylon membrane, and probed with mouse anti-PARP1. Reactions were set up as in (C), but without proteinase K digestion. Lane 1, PARP1 alone; lane 2, PAR reaction: PARP1, activated DNA and NAD; lane 3, 2-5A reaction: OAS1, pIC, and ATP; lane 4, 2-5A and PAR reactions: OAS1, pIC, and ATP with PARP1, activated DNA, NAD and histone; lane 5, 2-5A and PAR reactions without ATP. The large smeary signals are due to PAR chains attached to PARP1 and the smaller sharp bands are free PARP1. The same blot was probed with anti-PAR, anti-2-5A and anti-OAS1.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "HME cells expressing Flag-tagged OAS1, 2, or 3 were fixed and stained with anti-Flag. Scale bar, 10μm.",
    "ncbi_link": "Flag: 
OAS1: 4938"
  },
  {
    "caption": "HME control (v), KO1 and OAS1hi (O1hi) cells were pre-treated with IFNβ for 48 h. Cytoplasmic, membrane-bound and soluble nuclear fractions of cell lysates were analyzed by the Western method. Anti-AIF and anti-HDAC2 were used to characterize membrane and nuclear fractions, respectively; * indicates lanes where specific signals are detected.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "Same as (A), with lysates of HME control (vec) cells and cells expressing ectopic OAS1, OAS2 or OAS3 (OAS1-3hi). Experiments were repeated at least three times. Average lane densities normalized to vector are plotted below below as mean + SD, * p < 0.05 as assessed by Student's t-test.",
    "ncbi_link": "OAS1: 4938
OAS2: 4939
OAS3: 4940"
  },
  {
    "caption": "HME vec, KO1 and OAS1hi cells were incubated with olaparib for 30 min, then treated with 500 or 1000 μM of H2O2 and allowed to grow for 72 h. Bars represent means of triplicates ± SD from three experiments. * p<0.05; ** p<0.01 (relative to H2O2-treated vec cells) in Student's t-test.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "KO1 cells transfected with vector (KO1-vec), wild-type OAS1 (KO1-OAS1 wt), or mutant OAS1 (D75A/D77A, KO1-OAS1 mut) were treated with 500 μM of H2O2 for the indicated times and analyzed by the Western method. Loading controls: β-actin and overall protein levels were visualized by stain-free technology. The experiment was repeated three times; a representative image is shown.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "KO1 cells transfected with vector, wild-type OAS1 (OAS1 wt), or mutant OAS1 (D75A/D77A, OAS1 mut) were treated with 500 μM of H2O2. The accumulation of dead cells was measured with an IncuCyte ZOOM instrument. Means of triplicates ± SD. ****, p<0.001 in two-way ANOVA. The data represent the results of three experiments.",
    "ncbi_link": "OAS1: 4938"
  },
  {
    "caption": "(E) Phagocytosis of 3-µm beads was unchanged in MCOLN1-/- BMDMs, but was impaired using 6-µm beads (F), n = 89-157.",
    "ncbi_link": "MCOLN1: 94178"
  },
  {
    "caption": "Heterologous expression of mouse TPCs tagged with TagRFP-T (in red) rescues the phagocytic defect of Tpcn1-/- and Tpcn2-/- BMDM, but a pore-dead TPC2-mutant (N257A) does not, n = 39-94. Images taken 40 min post- 3-μm bead addition.",
    "ncbi_link": "Tpcn1: 252972
TPC2: 233979
Tpcn2: 233979"
  },
  {
    "caption": "Raising cytosolic Ca2+ with ionomycin (1 μM) rescues the Tpcn1-/- and Tpcn2-/- phagocytic defect, whilst UTP (100 μM) and ML-SA1 (50 μM) only weakly rescue (n = 84-192 cells).",
    "ncbi_link": "Tpcn1: 252972
Tpcn2: 233979"
  },
  {
    "caption": "RAW246.7 cells were transfected with either TPC1-TagRFP-T or TPC2-TagRFP-T (red) and presented with 3-µm opsonized beads labelled with Alexa Fluor 647 (blue). Acute time-series of bead engagement were collected. Contact between TPCs and beads are depicted in the time-stamped micrographs, where time is arbitrary after the start of the image stack (E,F) i.e. 110 s is still prior to engagement. The spatial relationship between TPCs and beads was quantified using a target graticule of 0.5-µm bands centred on the engulfed bead; the mean fluorescence within each band was normalized to the fluorescence of the maximum band and plotted against this radial distance (G,H); n = 35-36 cells.",
    "ncbi_link": "RFP-T: 
TPC1: 252972
TPC2: 233979"
  },
  {
    "caption": "RAW 247.6 macrophages loaded with a cytosolic chemical dye (Cyto dye) to detect global cytosolic Ca2+, and heterologously expressing (B) TPC1-G-GECO1.2 (TPC1-GG) or (C-E) TPC2-G-GECO1.2 (TPC2-GG) to detect peri-endo-lysosomal Ca2+ domains, which were not detected by (F) a TPC2 mutant (D276K)-G-GECO1.2 that blocks ion permeation or (A) unfused cytosolic G-GECO1.2 (Cyto GG). (A-F) Single-cell Ca2+ traces upon FcγR activation by opsonized 3-μm beads in -Ca2+o expressed as a percentage of the maximum fluorescence of the indicator, determined by adding 2 μM ionomycin and 10 mM CaCl2 at the end of each experiment (% Fmax) (D) TPC2-G-GECO1.2 activity was inhibited by 10 µM Ned-19, but was unaffected by (E) chelating global Ca2+ with EGTA/AM (100 μM for 2 min prior to bead addition). Summary data of the first spike from cells A-F (subsequent spikes show the same pattern; Appendix Fig. S4B), n = 87-274 cells; ***P<0.001 vs Cyto GG, ### P<0.001 vs TPC2-GG ctrl, ††† P<0.001 vs Cyto GG. Fusion of G-GECO1.2 to TPC2 did not alter the affinity of G-GECO1.2 for Ca2+ determined in permeabilized cells (n = 34-71 cells).",
    "ncbi_link": "G-GECO1.2: 
GG: 
TPC1: 252972
TPC2: 233979"
  },
  {
    "caption": "(I) Single-cell Ca2+ traces upon FcγR activation by opsonized 3-μm beads in -Ca2+o expressed as a percentage of Fmax. (I, J) Pre-emptying the ER stores with CPA or thapsigargin (Tg) abolished the global cytosolic Ca2+ response evoked by beads, but a TPC2-G‑GECO1.2 component remained, n = 17 - 121 cells.",
    "ncbi_link": "G‑GECO1.2: 
TPC2: 233979"
  },
  {
    "caption": "No local Ca2+ signal was detected with TPC2-G-GECO1.2 when Ca2+ spiking was evoked by ER-Ca2+ release with 100 μM UTP (K, L) or 10 μM CPA (M); only a bystander response equivalent to unfused cytosolic G-GECO1.2 was detected (n = 121-182 cells; *P<0.05).",
    "ncbi_link": "G-GECO1.2: 
TPC2: 233979"
  },
  {
    "caption": "Translocation of CB, a non-Ca2+ binding CB mutant (CB mut) or a triple mTagBFP2 (BFP) to the lysosome (LAMP1), as indicated by the increase in the Pearson's correlation coefficient was induced by 250 nM rapalog (30 mins) compared with ethanol (EtOH) control-treated RAW 247.6 cells. n = 11-25 cells; ***P<0.001.",
    "ncbi_link": "CB: 794"
  },
  {
    "caption": "When CB was brought to the lysosome (+rapalog) uptake of beads was inhibited, whilst the non-Ca2+ binding CB (CB mut; n = 46-187 cells) or triple mTagBFP2 (BFP; n = 38-52 cells) did not block phagocytosis;***P<0.001.",
    "ncbi_link": "BFP: 
BFP2: 
CB: 794"
  },
  {
    "caption": "RAW 247.6 macrophages expressing cytosolic G-GECO1.2 (Cyto GG), TPC2-G-GECO1.2 (TPC2-GG) or TRPML1-G-GECO1.2 (TRPML1-GG). (F) Single-cell Ca2+ traces upon FcγR activation by opsonized 3-μm or 6-μm beads in -Ca2+o expressed as a percentage of the maximum indicator fluorescence (% Fmax = 2 μM ionomycin and 10 mM CaCl2). (G) Summary of first Ca2+ spike; n = 69-121 (3-μm bead), 22-46 (6-μm beads) cells; ***P<0.001, **P<0.01 vs Cyto GG, ### P<0.001 TPC2-GG vs TRPML1-GG.",
    "ncbi_link": "G-GECO1.2: 
TRPML1: 57192
TPC2: 219931"
  },
  {
    "caption": "In WT BMDM, expression of a dominant-negative dynamin-2 mutant (Dyn2 K44A) reduced phagocytosis (n = 68-184). Expression of wildtype dynamin-2 (Dyn2) or constitutively active dynamin-2 (S764A mutant, mimicking the dephosphorylated state) in Tpcn1-/- macrophages restored phagocytosis of 3-μm beads after 10 min, n = 10-76 cells; ***P<0.001 vs WT control, ### P<0.001 vs Tpcn1-/- control.",
    "ncbi_link": "Dyn2: 25751
Dyn2: 13430
dynamin-2: 25751
dynamin-2: 13430
Tpcn1: 252972"
  },
  {
    "caption": "Single WT BMDM expressing HA-tagged dynamin-2 (immunolabelled with anti-HA, in red) undergoing phagocytosis of IgG-3-μm beads (blue). Images were taken 10 or 30 min post-addition of beads; actin (green) labelled with Phalloidin Alexa 488.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "Calcineurin inhibitors, FK506 (10 μM) or cyclosporin A (CsA, 10 μM) inhibited phagocytosis in WT cells, n = 65-159 cells. Ryngo (80 μM) rescued phagocytosis defects in Tpcn1-/- BMDM even in the presence of FK506 or CsA, n = 103-208 cells.",
    "ncbi_link": "Tpcn1: 252972"
  },
  {
    "caption": "Phagocytosis induced dephosphorylation of dynamin-2 (ratio of phospho-dynamin to total dynamin-2 expressed as a percentage of WT at time zero) in WT BMDM, but not in Tpcn1-/- BMDM; **P<0.01, ***P<0.001 (time-point matched unpaired t-test) n = 10-15. Measured using in-cell western assay, representative wells of plate image: total dyn2 (red) and phospho-dyn2 (green). See also Appendix Figures S6 and S7.",
    "ncbi_link": "Tpcn1: 252972"
  },
  {
    "caption": "RAW 246.7 macrophages expressing the dynein-binding protein (mTagBFP2-BicD2-FKBP12) for rapalog-induced lysosome repositioning to the MTOC, also co-expressed HsLAMP1-mCherry with or without a C-terminal FRB* (LAMP-FRB* or LAMP, in red). Cells were treated with 0.1% ethanol or 250 nM rapalog for 2 h. Only the tripartite complex of FKBP12-rapalog-FRB induced clustering of lysosomes at the MTOC (A, B). This clustering was selective for lysosomes because ER and mitochondria (KDEL-GFP and MitoTracker Green) were not affected (C). (A, B) Phagocytosis of IgG-3-μm beads was reduced by immobilizing lysosomes at the MTOC, n = 80-564 cells; ***P<0.001.",
    "ncbi_link": "mCherry: 
LAMP1: 3916"
  },
  {
    "caption": "Activation of dynamin-2 with Ryngo 1-23 or expression of constitutively active dynamin-2 (S764A mutant, expression confirmed by the grayscale image) restored phagocytosis of IgG-3-μm beads (n = 34-51 cells), but had no effect on the phagocytosis of IgG-6-μm beads, n = 36-72 cells (E); ***P<0.001 EtOH Ctrl vs rapalog Ctrl, ###P<0.001 rapalog Ctrl vs rapalog Ryngo/Dyn2S764A.",
    "ncbi_link": "Dyn2: 1785
dynamin-2: 1785"
  },
  {
    "caption": "A. Stills depicting actin flow in extracellular RH, myoA KO and adf KD parasites expressing Cb EmeraldFP. Continuous F-actin flow can be seen from the apical tip, to the Golgi region towards the posterior pole of the parasite. No difference can be observed between RH and myoA KO. For adf KD, the flow is completely abrogated. Red arrowhead marks the Golgi region, while the yellow arrowhead marks the apical nucleation centre. B. Skeletonisation processing of (A) depicting areas where F-actin dynamics/flow is prevalent. Individual signals for F-actin form a continuous, dynamic network that connects apical and posterior pole of the parasite. Red arrowhead marks the Golgi region nucleation centre, while the yellow arrowhead marks the apical nucleation centre. The images represent a projection of frames for each timepoint to provide a better overview of the dynamics of F-actin. C. Kymograph analysis of (A) and (B). The kymograph was generated by tracing a line in the middle of the parasite's body (red line). The colour-coded kymograph represents forward movement (red), backwards movement (green) and static F-actin (blue). The results demonstrate continuous exchange of F-actin from the apical to the posterior pole of the parasite within the cytosol of the parasite. This cytosolic exchange is similar in RH and myoA KO parasites, while completely abolished in the case of adf KD. Data information: Numbers indicate minutes:seconds; and Scale bars represent 5 µm.",
    "ncbi_link": "EmeraldFP: 
adf: 7893682
myoA: 7900154"
  },
  {
    "caption": "D. Top three rows: Parasites expressing Cb EmeraldFP along with myoA-SNAP before and after Ca2+-Ionophore (A23187) or BIPPO treatment. The parasites were also treated with 2 µM of Cytochalasin D or DMSO (as control) for 30 min. After addition of A23187, preferential relocalisation of actin can be observed at the apical tip, while addition of BIPPO caused F-actin accumulation at the basal end. 4th row: myoAKO parasites expressing Cb-EmeraldFP before and after treatment with A23187 and BIPPO. While no apical or basal accumulation of F-actin is observed, some peripheral location of F-actin occurs in presence of A23187 or BIPPO, preferentially in the apical half of the parasite. Bottom row: adf cKD parasites expressing Cb-EmeraldFP before and after treatment with Ca2+ Ionophore or BIPPO. No apparent change in F-actin localisation can be seen upon treatment. E. Skeletonization of movies shown in D. Before addition of A23187 or BIPPO, RH and myoA KO parasites behave similar with no accumulation of F-actin at the apical tip. After treatment with calcium ionophore A23187, preferential accumulation of F-actin at the apical tip can be observed for RH (red arrowhead), while BIPPO presented preferential accumulation in the basal end (red arrowhead). In myoA KO, some relocalisation of actin is observed at the periphery of the parasite (yellow arrowhead). In the case of adf cKD, no relocalisation occurs. The images represent a projection of frames for each timepoint to provide a better overview of the dynamics of F-actin.",
    "ncbi_link": "EmeraldFP: 
SNAP: 
adf: 7893682
myoA: 7900154"
  },
  {
    "caption": "C. Graph showing deformation of the whole parasite and its nucleus between invading and non-invading parasites. Indicated parasites were analysed. For adf cKD induced and non-induced conditions were compared, as indicated. 30 parasites were counted for each condition in triplicate. One-way ANOVA was used for statistical analysis and Tukey's multiple comparisons test. **** p value <0.0001. *** p value 0.0009. Data information: Error bars represent standard deviation. ; and Scale bars represent 5 µm.",
    "ncbi_link": "adf: 7893682"
  },
  {
    "caption": "A. Time-lapse analysis depicting invading RH adfcKD parasites expressing Cb-EmeraldFP. A F-actin ring can be observed at the TJ in the majority of cases (red arrowheads, first panel). Invasion can also occur without formation of an F-actin ring (second panel). During capped invasion, an F-actin ring is formed (third panel). Invasion of adf cKD parasites occurs without formation of an F-actin ring (fourth panel). F-actin accumulation is observed at the posterior pole of the parasite in all cases (orange arrows). Green segmented lines depict the area that was measured for generation of intensity plot profiles shown in (B). Yellow and purple dotted lines indicate the extra- and intracellular part of the parasite respectively. B. Intensity plot profiles of the movies shown in (A). Depicted plots correlate to half-invaded parasites. In the case of F-actin ring formation, two distinct peaks are detected, correlating to the F-actin ring at the TJ (red arrowhead) and the posterior pole of the parasite (orange arrow). In the case of no F-actin ring, no accumulation at the TJ can be observed; only the peak correlating to posterior F-actin can be detected. For adf cKD, only one peak can be seen corresponding to the posterior pole of the parasite. C. Quantification of F-actin accumulation at the TJ for RH Cb-EmeraldFP parasites as detected in time lapse analysis. The values are expressed as percentage. 28 total parasite invasion events were captured across three different biological replicates. Two-tailed unpaired t-test analysis was performed. **** p value <0.0001. Data information: Error bars represent standard deviation. White arrows point to direction of invasion. Scale bars represent 5 µm. ****p value <0.0001.",
    "ncbi_link": "EmeraldFP: 
adf: 7893682"
  },
  {
    "caption": "E. Tight Junction assay on fixed samples depicting invasion rates of indicated parasites. While in the majority of control parasites F-actin can be detected at the junction (~80%), no junctional ring can be detected in ~20% of all invasion events. In contrast, adf cKD, act1 cKO or myoA KO only show an overall invasion rate of ~20% compared to controls. In these cases junctional F-actin accumulation could never be detected. Note that the number of total invasion events for adf cKD, act1cKO and myoAKO correlates to the number of invasion events, seen for RH without F-actin ring formation. Data information: Error bars represent standard deviation. One-way ANOVA analysis was performed for each graph ****p value <0.0001.",
    "ncbi_link": "act1: 7896590
adf: 7893682
myoA: 7900154"
  },
  {
    "caption": "A. Time-lapse analysis of invading RH Cb-EmeraldFP parasites. During penetration, an F-actin ring is formed at the TJ (orange arrow). The nucleus (purple) is squeezed through the TJ (red arrowhead) and posterior F-actin appears to be directly connected to the nucleus and TJ (blue arrow). B. Analysis of nucleus deformation during live imaging shown in A. The nucleus constricts while its passing through the TJ (red arrowheads). C. The posterior end of the parasite deforms during the invasion process. F-actin is accumulated during invasion, with the posterior end contracting (blue arrow). Data information: Numbers indicate minutes:seconds. Scale bar represents 5 µm.",
    "ncbi_link": "EmeraldFP: "
  },
  {
    "caption": "D. Time-lapse stills depicting RH Cb-EmeraldFP parasites invading in absence of detectable F-actin at the junction (orange arrow). The nucleus (purple) is squeezed through the TJ (red arrowhead) during invasion. Actin accumulation at the posterior pole of the parasite is strongly detected in all cases (blue arrow). E. Analysis of nucleus deformation during live imaging shown in (D). The nucleus appears to not show constriction once its passing through the TJ when the F-actin ring is not present. F. The posterior end of the parasite also deforms during the invasion process.",
    "ncbi_link": "EmeraldFP: "
  },
  {
    "caption": "G. Z-stack gallery depicting mid-invading myoA KO parasites. Note that the nucleus is located located at the back during invasion events. Data information: Scale bar represents 5 µm. White arrow points to direction of invasion.",
    "ncbi_link": "myoA: 7900154"
  },
  {
    "caption": "A. SR-SIM images depicting invading parasites with and without the presence of the F-actin ring at the tight junction and invading adf cKD Cb-EmeraldFP parasites. SAG1 staining (in red) was performed prior to permeabilisation to specifically label extracellular part of the parasite. Note the accumulation of actin (blue arrow) around the nucleus and the posterior pole of the parasite, irrespective of F-actin ring formation at the TJ (orange arrowhead). 3D rendering is shown for each presented case (inlet). Data information: Scale bar represents 5 µm for SR-SIM images White arrow points to direction of invasion.",
    "ncbi_link": "EmeraldFP: 
adf: 7893682"
  },
  {
    "caption": "D. Quantification of perinuclear actin in indicated parasites. Parasites were counted by assessing Cb EmeraldFP signal as an actin marker around or in the vicinity of the nucleus. Still images to the right represent what was considered as F-actin - nucleus association. The orange arrowhead points to F-actin surrounding the nucleus in the posterior end of the parasite, the red and yellow arrowhead shows F-actin in the vicinity of the nucleus, hinting at a close interaction between the two. Three biological replicates were analysed with a minimum of 25 parasites per replicate. Data information: Error bars represent standard deviation. Scale bar represents 5 µm for SR-SIM images White arrow points to direction of invasion.",
    "ncbi_link": "EmeraldFP: "
  },
  {
    "caption": "E-G. SR-SIM images showing three stages of invading wt parasites. SiR-tubulin staining for microtubules (in red) was performed prior to fixation to specifically label microtubules in the parasite. During invasion, the microtubules (MT) are deformed at the TJ area (white arrowhead). Accumulation of actin (green arrow) at the posterior forms a F-actin meshwork. The nucleus is deformed when it enters the TJ area (orange arrowhead). H-J. In the case of the myoA KO strain, the MTs also deform when passing through the TJ (white arrowhead). However, F-actin is not concentrated at the posterior pole or the TJ, but evenly distributed within the cytosol of the parasite, with some peripheral location. K-M. In case of adfKD, MTs are deformed at the TJ area (white arrowhead). F-actin is accumulated at both ends of the parasite (green arrowheads), with no accumulation at the TJ. Data information: Scale bar represents 5 µm for SR-SIM images White arrow points to direction of invasion.",
    "ncbi_link": "adf: 7893682
myoA: 7900154"
  },
  {
    "caption": "A. Different invasion stages of P. falciparum merozoites expressing Cb-EmeraldFP. DAPI labels the nucleus (DNA), Cb-EmeraldFP labels actin filaments (CB-EME, green) and anti-RON4 labels the junction (red). Left panel: onset of invasion. Middle panel: A merozoite in the middle of invasion; note the constriction of the nucleus (blue) as it passes through the RON4 junction and F-actin colocalising with it (green). Right panel: A merozoite completing invasion; note the F-actin ring beyond the RON4-junction and actin filaments surrounding the nucleus. Data information: Scale bar represents 1 µm for Plasmodium falciparum",
    "ncbi_link": "EME: 
EmeraldFP: "
  },
  {
    "caption": "C. Super-resolution images showing various stages of invasion of erythrocytes by P. falciparum merozoites expressing Cb-EmeraldFP. Left panel: DAPI labels the nucleus (blue), Cb-EmeraldFP labels actin filaments (CB-EME, green) and the invasion junction is marked with an anti-RON4 antibody (red). Brightfield images have been marked with red dots depicting the junction, black dots depicting merozoite boundary still outside the erythrocyte and white dots depicting a merozoite that has penetrated the host cell. Top panel shows an attached merozoite beginning the process of invasion, the second panel during the process of invasion and the bottom two panels show merozoites completing the process of invasion. Right panel: Schematic depicting merozoite invasion into red blood cells. Letters depict the corresponding event in the model (left) and microscopy pictures (right). White arrows depict actin filaments that colocalise with the nucleus. D. Quantification of Plasmodium falciparum invasion events categorising actin-TJ and actin-nucleus association events. 121 events were counted in total. Data information: Error bars represent standard deviation. Scale bar represents 1 µm for Plasmodium falciparum",
    "ncbi_link": "EME: 
EmeraldFP: "
  },
  {
    "caption": "(A) Representative flow cytometry plots (left) and pooled data (right) of competition assays with sgControl and sgRnf31 B16-F10 ova tumor cells after culture with the indicated recombinant cytokine(s) (10 ng/mL) for 48 hours; n.s.: no significance, ****p < 0.0001, Unpaired t-test for n = 3 biological replicates. Pooled data are represented as mean ± SEM.",
    "ncbi_link": "Rnf31: 268749"
  },
  {
    "caption": "(B) CRISPR/Cas9 screen showing depleted B16-F10 genes after one week culture with TNF + IFN-γ (both 10 ng/mL); blue genes indicate overall genes with p < 0.001, black genes indicate genes of interest with p < 0.05. Significance assessed using MAGeCK test.",
    "ncbi_link": "CRISPR: 
Cas9: 57852564"
  },
  {
    "caption": "(H) Representative flow cytometry plots (left) and pooled data (right) showing PI staining of sgControl or sgRNF31 A375 tumor cells after culture with the indicated recombinant cytokine(s) (10 ng/mL) for 48 hours; n.s.: no significance, *p < 0.05, **p < 0.01, Unpaired t-test for n = 3 biological replicates. Pooled data are represented as mean ± SEM.",
    "ncbi_link": "RNF31: 55072"
  },
  {
    "caption": "(A) PI staining of sgControl or sgRnf31 B16-F10 tumor cells treated with combined TNF/IFN-γ (both 10 ng/mL) for 24 hours in the absence and presence of QVD-OPh (10 μM); n.s.: no significance, ***p < 0.001, ****p < 0.0001, Unpaired t-test for n = 3 biological replicates. Pooled data are represented as mean ± SEM.",
    "ncbi_link": "Rnf31: 268749"
  },
  {
    "caption": "(B) Western blot analysis of the indicated proteins on whole cell lysates for sgControl or sgRnf31 B16-F10 tumor cells cultured with the indicated cytokine(s) (10 ng/mL for all) for 0, 3, 6, or 9 hours; β-actin was used as a loading control.",
    "ncbi_link": "Rnf31: 268749"
  },
  {
    "caption": "(D) CRISPR/Cas9 screen showing enriched genes from sgRnf31 B16-F10 tumor cells after successive treatment with combined TNF/IFN-γ, as described in (C); red genes indicate overall genes with p < 0.0001. Significance assessed using MAGeCK test.",
    "ncbi_link": "CRISPR: 
Cas9: 57852564
Rnf31: 268749"
  },
  {
    "caption": "(G) PI staining of sgControl, sgRnf31, sgRnf31/Stat1, sgRnf31/Casp8, sgRnf31/Bid, or sgRnf31/Rela B16-F10 tumor cells treated with combined TNF/IFN-γ for 24 hours; *p < 0.05, ****p < 0.0001, asterisk(s) indicated group vs TNF/IFN-γ-treated sgRnf31 group, Unpaired t-test for n > 3 biological replicates. Pooled data are represented as mean ± SEM.",
    "ncbi_link": "Bid: 12122
Casp8: 12370
Rela: 19697
Rnf31: 268749
Stat1: 20846"
  },
  {
    "caption": "(B) Individual (left) and average (right) in vivo growth of subcutaneous wild-type or sgRnf31 B16-F10 ova tumors left untreated or treated with adoptively transferred OT-I CD8+ T cells (on days indicated by black arrows); *p < 0.05, **p < 0.01, Unpaired t-test for OT-I-treated wild-type vs OT-I-treated sgRnf31 with n = 5/6 mice per group. Pooled data are represented as mean ± SEM.",
    "ncbi_link": "Rnf31: 268749"
  },
  {
    "caption": "(a) RV-infected   MA-NSP5-EGFP cells at 6 HPI. NSP5-EGFP-tagged viral factories (green) are dissolved in the presence of 4.7% (v/v) propylene glycol (PG, middle). Viral RNA-protein condensates rapidly reform (<10 min) after replacing the PG-containing cell culture medium (PG removed, right). Seg3 (magenta) and Seg4 (cyan) transcripts are detected by smFISH, and colocalising Seg3 and Seg4 RNA signals (white). Scale bars: 50 µm, zoomed-in regions: 10 µm.",
    "ncbi_link": "EGFP: 
MA: 
NSP5: 
Seg3: 
Seg4: "
  },
  {
    "caption": "(e) 3D DNA-PAINT analysis of Seg3 RNA foci in RV-infected cells at 4 and 6 HPI. Scale bars, 2 µm (left) and 200 nm (zoomed-in, right). (f-g) Distribution of calculated volumes and sphericities of the Seg3  RNA-containing granules in  RV-infected cells at 4 HPI (N=704) and 6 hpi (N=698), shown in (e). Box plots represent the 25th/75th interquartile range, with whiskers representing the 5th/95th percentile values. Medians shown as central bands, and means shown as squares. Symbol 'x' denotes 1% and 99% percentile values, and min and max values are shown as '-'. At the 0,001 level, the two distributions are significantly different between 4 and 6 hpi, assessed by the two-sample Kolmogorov-Smirnov test.",
    "ncbi_link": "Seg3: "
  },
  {
    "caption": " [a] Sagittal  sections obtained from mice (p15) of the indicated genotypes were immunostained  for ADP-ribose using the pan-ADP-ribose detection reagent MABE1016. Representative  images showing levels of ADP-ribose in the hippocampal regions CA1, CA3, and dentate gyrus (DG), and in the cerebral cortex. Red dotted boxes highlight the elevated ADP-ribose staining in Xrcc1Nes-Cre cerebellum (left dotted box) and hippocampus (right doted box). Scale bars: 5 mm, 50 μm. WT (n = 4 mice), Xrcc1Nes-Cre (n = 4), Parp1+/- /Xrcc1Nes-Cre (n = 4), Parp1-/-/Xrcc1Nes-Cre (n = 3) and Parp1-/- (n = 3). Summary histograms show mean ± SEM. Pairwise comparisons between WT versus Xrcc1Nes-Cre mice and WT versus Parp1-/-/Xrcc1Nes-Cre mice  were conducted by Kruskal-Wallis ANOVA with Dunn's post-hoc test and statistically significant differences (*p<0.05) are shown. ",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": " [b] Protein extracts from wild type (WT), Xrcc1Nes-Cre, and Parp1-/- forebrain tissue, containing hippocampus and cortex, were incubated with 1 mM NAD+ for 45 min in the presence or absence of PARP inhibitor as indicated, and ADP-ribosylation  detected by western blotting using the poly(ADP-ribose)-specific detection reagent MABE1031. Representative images from two or more independent experiments are shown. A western blot showing the level of Parp1 and Xrcc1  in the  forebrain tissue extracts is also shown, Inset. ",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": " [b] Video monitoring and recording of generalised running/bouncing seizures in mice of the indicated genotypes from P15-P19. The point of death of Xrcc1Nes-Cre mice  by fatal seizure is indicated (cross). Note no  seizures from mice of other genotypes were detected. WT (n = 9 mice), Xrcc1Nes-cre (n = 3 mice), Parp1+/- /Xrcc1Nes-Cre (n = 3 mice), and Parp1-/-/Xrcc1Nes-Cre  (n = 3). ",
    "ncbi_link": "Cre: 2777477
cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": " [b] Heatplots of cumulative SLEs: WT (n=11 slices from 3 mice), Xrcc1Nes-Cre (n=12 slices from 4 mice), Parp1+/-/Xrcc1Nes-Cre (n=12  slices from 3 mice) and Parp1-/-/Xrcc1Nes-Cre  (n=10 slices from 3 mice). Each horizontal bar corresponds to one  slice with the colour code indicating cumulative SLEs. ",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": " [e] Summary histograms (mean ± SEM) of cumulative seizure-like activity at 5, 10, and 15 min timepoints in cortex, CA1, and CA3  regions of wild type and Xrcc1Nes-Cre brain slices from mice treated or not for 5-8 days ad libitum with PARP1 inhibitor (ABT-888) prior to analysis. WT (n = 8 slices from 4 mice), Xrcc1Nes-Cre (n = 10 from 5 mice), WT +  PARPi (n = 6 from 3 mice), Xrcc1Nes-Cre + PARPi  (n = 9 from 3 mice). Pairwise comparisons at the 15 min time point between WT versus Xrcc1Nes-Cre mice and WT versus Xrcc1Nes-Cre mice  +  PARPi were conducted by Kruskal-Wallis with Dunn's post-hoc tests and statistically significant differences (*p<0.05) are shown. ",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Xrcc1: 22594"
  },
  {
    "caption": " [a] Representative  images of indirect immunofluorescence of DIV6 hippocampal neurons cultured from P1 WT and Xrcc1Nes-Cre mouse pups, immunostained for ADP-ribose  (red), NeuN  to identify neurons (green), and counterstained with DAPI  (blue). Cells were pretreated with PARP inhibitor (10 µM) or vehicle for 2 h prior to fixation, with PARG  inhibitor (10 μM) additionally present for the final hour. Scale bar 10 µm. [b] Histogram of mean (± SEM) relative pan-ADP-ribose fluorescence in NeuN-positive hippocampal neurons pretreated with PARP inhibitor (5 µM) or vehicle for 5 h prior to fixation, with PARG inhibitor (10 μM) additionally present for the final hour. Neurons were cultured from WT (n = 6 mice, > 180 cells per condition), Xrcc1Nes-Cre (n = 6, > 180), Parp1+/-/Xrcc1Nes-Cre (n = 3, > 90), and Parp1-/-/Xrcc1Nes-Cre (n = 3, > 90). * indicates significant differences from WT (Kruskal-Wallis ANOVA, p = 0.0013 and Dunn's post-hoc tests). ",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": "Summary histogram of the mean (± SEM) of the integrated fluorescence responses for all individual synapses for each condition. Synapse number is the same as in (D-F). Responses are significantly higher in Xrcc1Nes-Cre synapses  versus both WT and Parp1-/-/Xrcc1Nes-Cre (one-way ANOVA, *p < 0.0033, and pairwise student's t-tests).",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Parp1: 11545
Xrcc1: 22594"
  },
  {
    "caption": "C-D: Confocal  images (C) and quantification (D) of immunofluorescence staining  of STAT5b,  actin filaments (phalloidin) and nuclei  (DAPI) in cardiomyocytes  of cryosections from the hearts  of mice  transduced with either control- or ERBB4ECD-AAV. Panel D depicts quantification of colocalization  of STAT5b- and DAPI-specific signals. One dot in the boxplot corresponds to the median value in 20-50 images of stained  sections from one heart  (control AAV: n = 4, ERBB4ECD-AAV: n=5, biological replicates). Two-tailed unpaired T-test was used for statistics. Scale bar 10µm. White arrows point to cardiomyocyte nuclei. Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "ERBB4: 13869"
  },
  {
    "caption": "E: Real-time RT-PCR  analysis of expression of the indicated STAT5b  target genes in the heart  of mice  transduced with either control- or ERBB4ECD-AAV. One dot corresponds to analysis of one heart  (n = 10; biological replicates combined from two replicate experiments). Two-tailed unpaired T-test was used for statistics. Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "ERBB4: 13869
STAT5b: 20851"
  },
  {
    "caption": "F-G: Confocal  images (F) and quantification (G) of immunofluorescence staining  of myosin heavy chain in primary mouse cardiomyocytes. The cells were treated with either control or Stat5b-targeting shRNAs and stimulated with NRG-1 for two days. Myosin  immunoreactivity was used to quantify  cell area. One dot in the boxplot corresponds to one cell (Control no NRG-1: n = 83, control with NRG1: n=73, Stat5b#1 with NRG-1: n=80, Stat5b#2 with NRG1: n=75; technical replicates combined from four biological replicate experiments). Non-parametric Kruskal-Wallis ANOVA was used. Post hoc analyses were conducted with the Mann Whitney U-test and the resulting P-values corrected with the method of Benjamini, Krieger and Yekutieli. Scale bar 20µm. Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "Stat5b: 20851"
  },
  {
    "caption": "H-I: Confocal  images (H) and quantification (I) of immunofluorescence staining  of STAT5b  and nuclei  (DAPI) in mouse cardiomyocytes. The cells were treated with either control or Erbb4-targeting shRNAs. Panel I depicts quantification of colocalization  of STAT5b- and DAPI-specific signals (left) and the cell perimeter  (right). One dot in the boxplots corresponds to one cell (Control: n = 24, Erbb4#1: n=26, Erbb4#2: n=35; technical replicates combined from two biological replicate experiments). Non-parametric Kruskal-Wallis ANOVA and Dunn's multicomparison test (colocalization  analysis) and Brown-Forsythe one-way ANOVA and Dunnett's multicomparison test (cardiomyocyte  size analysis) with multiple test correction were used for statistics. Scale bar 20µm. Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "Erbb4: 13869"
  },
  {
    "caption": "J:  Real-time RT-PCR   analysis of expression of the indicated STAT5b   target genes in mouse cardiomyocytes. The cells were treated with either control, Stat5b- or Erbb4-targeting shRNAs and stimulated with NRG-1 for 30 minutes. One dot corresponds to the mean of technical repeats in one experiment and the whiskers the standard deviation (for each group n = 3; biological replicate experiments). One-way ANOVA and the Dunnett's multicomparison test with multiple test correction was used for statistics. *, P ≤ 0.05; ** P < 0.01; ***, P < 0.001 against control shRNA (Igf-1  panel: Stat5b#1 P = 0.0038, Stat5b#2 P = 0.0153,  Erbb4#1 P = 0.0188, Erbb4#2 P = 0.0288; Myc  panel: Stat5b#1 P = 0.0093, Stat5b#2 P = 0.0119, Erbb4#1 P = 0.0197,  Erbb4#2 P = 0.0512; Cdkn1a  panel: Stat5b#1 P = 0.0091, Stat5b#2 P = 0.0107,  Erbb4#1 P = 0.0235,  Erbb4#2 P = 0.048). Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "Cdkn1a: 12575
Erbb4: 13869
Igf-1: 16000
Myc: 17869
STAT5b: 20851
Stat5b: 20851"
  },
  {
    "caption": "G: Real-time RT-PCR  analysis of expression of the indicated STAT5b  target genes in primary mouse cardiomyocytes  treated for 1-3 hours with the DMSO  buffer, the ERBB  kinase inhibitor AG1478, or dynasore, and stimulated or not for 30 minutes with  NRG-1. One dot corresponds to the mean of technical repeats in one experiment and the whiskers the standard deviation (for each group in  Igf-1 and Cdkn1a  panel: n = 6, for each group expect the dynasore  group in Myc  panel: n=4, for the dynasore  group in Myc  panel: n=3 ; biological replicate experiments). One-way ANOVA and the Dunnett's multicomparison test with multiple test correction was used for statistics. *, P < 0.05; ** P < 0.01; ***, P < 0.001; against DMSO  + NRG-1 treatment (Igf-1 panel: DMSO  without NRG-1 P = 0.0041, AG1478 P = 0.0082, dynasore P = 6.61e-06; Myc  panel: DMSO  without NRG-1 P = 0.0386, AG1478 P = 0.0037, dynasore P = 0.0064; Cdkn1a  panel: DMSO  without NRG-1 P = 0.0123, AG1478 P = 0.0064, dynasore P = 0.0092). Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "Cdkn1a: 12575
Igf-1: 16000
Myc: 17869
STAT5b: 20851"
  },
  {
    "caption": "A-B: Confocal  images (A) and quantification (B) of immunofluorescence staining  of  myosin heavy chain and Stat5b  in hearts  of 4 dpf zebrafish embryos  injected with CRISPR/Cas9  and either control or stat5b-targeting gRNA at one-cell stage. The myosin  immunoreactivity was used to quantify the average thickness of the ventricular wall and the cross-sectional area of the ventricles. Stat5b staining  intensity was also quantified. One dot in the boxplots corresponds to one heart (control gRNA: n = 14, stat5b  gRNA n = 13; biological replicates from one of three replicate experiments). Unpaired two-tailed T-test was used for statistics. Scale bar 50µm. Data information: For all boxplots the central band represents the median, the box the interquartile range and whiskers the whole range of values.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
stat5b: 445474"
  },
  {
    "caption": "At 72 h after transfection with siRNA duplexes for BAG6 or control siRNA (10 nM each), the intracellular localization of TfnR in HeLa cells was examined (shown as green). Nuclear DNA was stained with Hoechst 33342 (shown as blue). Control knockdown (left panel), Rab8a knockdown (center panel), and BAG6 knockdown (right panel).",
    "ncbi_link": "BAG6: 7917
Rab8a: 4218"
  },
  {
    "caption": "Knockdown of Rab8a (with Rab8a siRNA#1, #2, and #3) stimulated the accumulation and stabilization of Ptc1 protein in HEK293 cells.",
    "ncbi_link": "Rab8a: 4218"
  },
  {
    "caption": "Knockdown of BAG6 (with BAG6 siRNA#1) stimulated the accumulation and stabilization of Ptc1 protein in HEK293 cells.",
    "ncbi_link": "BAG6: 7917"
  },
  {
    "caption": "BAG6 protein co-precipitated Rab8a, while neither Rab7 nor Rab11a were co-precipitated with BAG6. Flag-tagged Rab8a, Rab7, Rab11a, and luciferase-CL1 (Lc-CL1; a positive control) were expressed in HeLa cells and the cells were treated with 10 μM MG-132 for 4 h. Flag-immunoprecipitates were blotted with anti-BAG6 and anti-Flag antibodies, respectively. Note that all cells used were treated with 10 μM MG-132 for 4 h.",
    "ncbi_link": "CL1: 
Flag: 
Lc: 
luciferase: 
Rab11a: 8766
Rab7: 7879
Rab8a: 4218"
  },
  {
    "caption": "Deficiency of Rabin8, a GEF for Rab8a, enhanced the physical interaction between BAG6 and WT Rab8a proteins. Flag-tagged WT Rab8a was expressed in Rabin8 siRNA-treated cells, and Flag immunoprecipitates were probed with an anti-BAG6 antibody. Note that all cells used were treated with 10 μM MG-132 for 4 h.",
    "ncbi_link": "Flag: 
Rabin8: 117177
Rab8a: 4218"
  },
  {
    "caption": "The N-terminal GTPase domain of Rab8a was essential for BAG6 recognition. A series of Flag-tagged truncated fragments of WT Rab8a were expressed in HeLa cells with S-tagged BAG6 and treated with (+) or without (-) protease inhibitors for 4 h. Flag-Rab8a substrates were immunoprecipitated and probed with an anti-BAG6 antibody.",
    "ncbi_link": "Flag: 
S-tagged: 
BAG6: 7917
Rab8a: 4218"
  },
  {
    "caption": "Kyte-Doolittle hydrophobicity plots of the complete amino acid sequence of human WT Rab8a and T22N-3IS mutant. The hydrophobicity peak within WT Switch I was abolished in the 3IS mutant (indicated within the red box). The numbers on the horizontal axis denote the corresponding amino acid positions in these proteins.",
    "ncbi_link": "Rab8a: 4218"
  },
  {
    "caption": "Rab8a (T22N) protein accumulated in BAG6-knockdown cells. HeLa cells were transfected with siRNA duplexes for BAG6 or control siRNA. At 48 h after siRNA transfection, Flag tagged-Rab8a (T22N) was expressed in the cells. At 24 h after Rab8a (T22N) transfection, the cells were chased with 50 μg/mL CHX and harvested at the indicated time after CHX addition. Actin was used as a loading control.",
    "ncbi_link": "Flag: 
BAG6: 7917
Rab8a: 4218"
  },
  {
    "caption": "Anti-Flag blot signals in the control or BAG6 siRNA-treated cells were quantified, and relative signal intensities after CHX addition were calculated. The value of the Flag signal at 0 h was defined as 1.0. Note that all signal intensities of the Flag-tag were normalized by that of actin, a loading control, in each sample.",
    "ncbi_link": "BAG6: 7917"
  },
  {
    "caption": "Polyubiquitin modification of Rab8a was abolished in BAG6-knockdown cells. Flag-Rab8a (T22N) immunoprecipitates were blotted with an anti-polyubiquitin antibody (FK2, left panel). As a negative control, siRNA#1scr was used. Anti-polyubiquitin signals co-precipitated with Rab8a (T22N) (a representative example is shown in the left panel) were quantified (right panel). Note that the intensities of the co-precipitated polyubiquitin signal were normalized both by the input ubiquitin-signal and bait Flag-signal.",
    "ncbi_link": "BAG6: 7917"
  },
  {
    "caption": "BAG6 knockdown induced the abnormal distribution of Golgi apparatus markers. Representative images of the trans-Golgi membrane protein Stx6 (green) in BAG6-suppressed CHO cells with a Chinese hamster-specific siRNA (cBAG6 siRNA#2). Scale bar: 10 μm (A). Fluorescent signals were detected using a laser scanning confocal microscopy system. Nuclei were stained by Hoechst (blue).",
    "ncbi_link": "BAG6: 100763893"
  },
  {
    "caption": "BAG6 knockdown induced the abnormal distribution of Golgi apparatus markers. Images of the cis-Golgi membrane protein GS28 and the cis-Golgi matrix protein GM130 in BAG6-suppressed CHO cells with another Chinese hamster-specific siRNA (cBAG6 siRNA#5). GS28 (green) and GM130 (red) are indicated by arrowheads. Scale bar: 10 μm. (B). Fluorescent signals were detected using a laser scanning confocal microscopy system. Nuclei were stained by Hoechst (blue).",
    "ncbi_link": "BAG6: 100763893"
  },
  {
    "caption": "Glycosylation of the IL-2Rα transmembrane protein was not reduced by BAG6 knockdown. Flag-tagged WT IL-2Rα protein was expressed in HeLa cells with (+) or without (-) BAG6 siRNA, and was immunoprecipitated with an anti-Flag antibody. The precipitates were incubated with (+) or without (-) 10 unit of the deglycosylation enzyme PNGase F, and subjected to Western blot analysis with an anti-Flag antibody. Low-mobility (indicated as glycosylated) and high mobility (indicated as non-glycosylated) signals of WT IL-2Rα are indicated.",
    "ncbi_link": "Flag: 
BAG6: 7917
IL-2Rα: 3559"
  },
  {
    "caption": "Defects in the distribution of cell surface glycoproteins in BAG6-suppressed cells. The graph quantitatively displays the number of fluorescence counts per cell as the mean ± S.D. calculated from 10 independent biological replicates (E).",
    "ncbi_link": "BAG6: 7917"
  },
  {
    "caption": "Defects in the distribution of cell surface glycoproteins in BAG6-suppressed cells. Lectin GS-II-derived cell surface signals were counted using ImageJ software. SRP54 knockdown was used as a positive control for this experiment t-test). Cell surface fluorescent signals were detected by confocal microscopy without plasma membrane permeabilization. BAG6 siRNA down-regulated the cell surface expression of glycoproteins (F).",
    "ncbi_link": "BAG6: 7917
SRP54: 6729"
  },
  {
    "caption": " E. HeLa/GFP-DNMT1 cells transfected with indicated siRNAs were processed as in (D). ",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": " J. GFP-tagged DNMT1 from extracts of HeLa/GFP-DNMT1 cells treated or not with 5-azadC was immobilized on GFP-Trap agarose, subjected to stringent washing to remove proteins non-covalently bound to GFP-DNMT1 and incubated with recombinant HA-ubiquitin, E1 and E2 (UbcH5a) enzymes and RNF4 proteins (STUbL reaction) at 37 °C for 1 h. Samples were then subjected to immunoblotting to assay for RNF4-dependent STUbL activity towards GFP-DNMT1. ",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": " J. HeLa or HeLa/GFP-DNMT1 cells left untreated or exposed to 5-azadC for 30 min were lysed and subjected to GFP IP under stringent conditions. After extensive washing, individual IPs were incubated with an equal amount (800 μg) of whole cell lysate of HeLa cells transfected with Myc-PIAS4 expression construct (Fig. EV2J), washed and immunoblotted with antibodies to Myc, SUMO2/3 and GFP. *, cross-reactive band. ",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": " K. HeLa/GFP-DNMT1 cells transfected with previously validated siRNAs targeting established SUMO E3 ligases (Fig. EV2L and Methods section) were treated with 5-azadC for 30 min, collected and subjected to GFP immunoprecipitation under denaturing conditions, and immunoblotted with antibodies to SUMO1, SUMO2/3, ubiquitin and GFP. ",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": " J. As in (I), but using RNF4-depleted CSF-arrested extracts reconstituted with recombinant RNF4 WT or C130A from (H). ",
    "ncbi_link": "RNF4: 495944///496368"
  },
  {
    "caption": " L. p4xDPCSUMO was subjected to sequential addition of NPE and CSF-arrested extract as in (I). CSF-arrested extracts from (K) were supplemented with recombinant RNF4, and the DPC plasmid was recovered by DPC pull-down at the indicated time points and immunoblotted against M.HpaII. ",
    "ncbi_link": "RNF4: 495944///496368"
  },
  {
    "caption": " E. HeLa cells transfected with RNF4 siRNA were synchronized in early S phase by double thymidine block. Six h after release from the block, cells were pulse-labeled with 5-azadC for 30 min. Mitotic cells were isolated by shake-off 8 h later, washed and incubated or not with MPS1 inhibitor (MPS1i) and collected at the indicated times. Cells were then processed for immunoblotting with indicated antibodies. ",
    "ncbi_link": "RNF4: 6047"
  },
  {
    "caption": "B Representative examples of chromatin  accessibility and gene expression of KRT5  and KRT10, two key epidermal differentiation-related genes, in the main keratinocyte  populations.",
    "ncbi_link": "KRT10: 3858
KRT5: 3852"
  },
  {
    "caption": "C Upper: Heatmaps displaying the unsupervised clustering of 67 AK/cSCC  and healthy controls based on the methylation  patterns of the MIR200C/141 cluster and the MIR205  gene. Lower: Bar plots showing the quantification of the methylation  values at CpGs  located at promoter regions in each cell-of-origin-based subclass. For the MIR200C/141 cluster, probes located at the regulatory CpG  island are depicted with green arrows. For the MIR205  gene, all probes shown in the heatmap are part of the promoter region and were used for quantification. Data information: AK:  actinic keratosis, cSCC: cutaneous squamous cell carcinoma.",
    "ncbi_link": "MIR200C: 406985
MIR205: 406988"
  },
  {
    "caption": "Non-endosomal ubiquitin-positive structures accumulate in ESCRT depleted cells. HeLa cells were left untransfected (A) or transfected with control (B), Hrs (C), Tsg101 (D), Vps22 (E), or Vps24 (F) siRNA for 5 d and processed for immunofluorescence microscopy. Cells were labeled with antibodies against EEA1 (blue), ubiquitin (mono and poly-Ub, red), and Lamp2 (green). Colocalization between EEA1 and Ub is indicated in purple and between Ub and Lamp2 in yellow. Bar, 10 μm. Single channel images of the insets are shown in Fig. S1 (available at http://www.jcb.org/cgi/content/full/jcb.200702115/DC1).",
    "ncbi_link": "Vps22: 25978
Vps24: 51652
Hrs: 9146
Tsg101: 7251"
  },
  {
    "caption": "p62- and Alfy-positive structures accumulate in cells depleted of Tsg101 or Vps24. HeLa cells transfected with siRNA against Tsg101 or Vps24 were fixed, permeabilized, and stained with antibodies against ubiquitin (red) and p62 (green) (A) or against ubiquitin (green) and Alfy (red) (B). Colocalization is indicated in yellow. Bar, 10 μm. (C) The number and size (area) of p62-positive particles were quantified using ImageJ software. Approximately 100 cells from three different experiments (n = 334 (control), 309 (Tsg101), and 246 (Vps24)) were used for the quantification and the data is presented as average number per 100 cells. Error bars = SEM.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "Autophagic degradation is impeded in Tsg101- and Vps24-depleted cells. HeLa cells stably expressing GFP-LC3 (green) were transfected with control (A), Vps24 (B), or Tsg101 (C) siRNA for 5 d and processed for immunofluorescence analysis. Cells were labeled with antibodies against p62 (red) and analyzed by confocal microscopy. Colocalization is indicated in yellow. Bar, 10 μm.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "(D) The total level of p62 and GFP-LC3 (normalized to control cells) and their degree of colocalization (% of total) in control and Tsg101- and Vps24-depleted cells were quantified using the Zeiss LSM 510 Meta software. 30 cells from three independent experiments were used for quantification. Error bars = SEM.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "(E) Western blot showing accumulation of LC3-II and p62 in HeLa cells depleted of Vps24 and Tsg101. p62 also accumulates in the insoluble fraction (bottom picture), indicating a shift to a more aggregated form upon depleted of Vps24 and Tsg101.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "(F) Western blot showing that LC3-II levels were similar in control and Vps24-depleted cells treated with Bafilomycin A.",
    "ncbi_link": "Vps24: 51652"
  },
  {
    "caption": "Formation of autolysosomes is inhibited in cells depleted of Tsg101 or Vps24. (A) The double-tagged LC3 protein (mCherry-GFP-LC3) will emit yellow (green merged with red) fluorescence in non-acidic structures and appear as red only in the autolysosomes due to quenching of GFP in these acidic structures. (B-F) HeLa cells were transfected with control (B), Tsg101 (C), or Vps24 (D) siRNA for 4 d and then with mCherry-GFP-LC3 for another 24 h before confocal microscopy analysis. Bar, 5 μm",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "Autophagosomes and amphisomes do form in ESCRT-depleted cells. HeLa cells stably expressing GFP-LC3 were transfected with control (A), Tsg101 (B, D, and E), or Vps24 (C) siRNA and processed for immuno-EM analysis. Cryosections were incubated with antibodies against GFP (15-nm gold) and LBPA (10-nm gold). Amphisomes (Am), characterized by their content of electron-dense LC3-positive areas and intraluminal vesicles, were observed in both control (A) and ESCRT-depleted cells (B and C). (D) In the Tsg101-depleted cells we found large clusters of more typical autophagosomes (Au) and (E) clusters of double-membrane structures, consisting of autophagosomes and tubular structures which might represent phagophores, all labeling strongly for GFP-LC3. We never observed similar clusters in control cells and very rarely in Vps24-depleted cells. Bars, 200 nm. (F) Quantification of amphisomes in control cells and cells depleted for Tsg101 or Vps24. Approximately 20 cells were included per siRNA depletion per experiment (n = 3). Error bars = SEM.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "Immuno-EM of p62-positive structures in Vps24- and Tsg101-depleted cells. Cryosections of HeLa cells transfected with Vps24 (A, C, and E) or Tsg101 (B, D, and F) siRNA were incubated with antibodies against p62 (15-nm protein A gold, 10-nm in D). Membrane-free p62-positive aggregates (C and D) or p62-positive structures contained within dense clusters of vesicular-tubular elements (A and B) were detected. Vesicles with early endosomal morphology (EE) or multivesicular appearance (MVB) associated with these clusters. We also observed p62 labeling in electron-dense structures sequestered within amphisomes in cell depleted of Vps24 (E) or Tsg101 (F). The amphisomes typically consist of an electron-dense p62 positive body (E and F, arrowhead), and a multivesicular endosomal structure (E and F, arrow). Bars, 200 nm.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "Ubiquitin and p62 positive structures accumulate in cells expressing CHMP2 mutants. HeLa cells transfected with myc-tagged wild-type CHMP2B (A), CHMP2BIntron5 (B), or CHMP2BΔ10 (C) were labeled with antibodies against c-Myc (red), ubiquitin (green), and p62 (blue) and analyzed by confocal microscopy. Single channel images in black and white are shown. Bars,10 μm.",
    "ncbi_link": "CHMP2: 25978
CHMP2B: 25978"
  },
  {
    "caption": "(E) Western blot analysis showing accumulation of p62 in cells transfected with myc-CHMP2BIntron5 compared with mock-transfected cells (control) and cells transfected with CHMP2Bwt",
    "ncbi_link": "CHMP2B: 25978"
  },
  {
    "caption": "(F) Immuno-EM showing p62-positive aggregates containing dense clusters of vesicular-tubular structures in cells transfected with myc-CHMP2BIntron5. Bar, 200 nm.",
    "ncbi_link": "CHMP2B: 25978"
  },
  {
    "caption": "TDP-43 accumulates in cytoplasmic ubiquitin-positive structures in Tsg101- and Vps24-depleted cells. HeLa cells transfected with control (A), Tsg101 (B), or Vps24 (C) siRNA were fixed, permeabilized, and stained with antibodies against TDP-43 (green), ubiquitin (red), and p62 (blue). Single channel images in black and white are shown. Colocalization of all proteins is indicated in white in the merged picture. Bars, 10 μm.",
    "ncbi_link": "Vps24: 51652
Tsg101: 7251"
  },
  {
    "caption": "Vps24 is required for efficient clearance of Htt inclusions. HeLa cells expressing HttQ65-mCFP (A) or HttQ103-mCFP (B) and N2a cells expressing HttQ103-mCFP (C) were transfected with control or Vps24 siRNA for 2 d and then incubated in the absence or presence of doxycycline for 3 d to turn off expression of HttQ65/Q103-mCFP. Vps24 depletion was determined by Western blot analysis. (A and C) Clearance of SDS-insoluble Htt inclusions was analyzed by filter-trap assays. (B) Alternatively, aggregate clearance was analyzed by confocal quantification of the number of HeLa HttQ103 cells having visible inclusions after 3 d in the absence or presence of dox. 300 cells from three independent experiments were counted for each condition. Error bars = SD.",
    "ncbi_link": "Vps24: 51652
Htt: 3064"
  },
  {
    "caption": "(a) Knockdown of dRagA and dRagC decreased dS6K phosphorylation (Thr 398). Drosophila S2 cells untreated (lane 2) or treated with the indicated RNAi were starved of amino acids for 1 h followed by amino acid stimulation for 30 min Phosphorylation and protein levels of dS6K were determined by immunoblotting with the indicated antibodies.",
    "ncbi_link": "dRagA: 41071
dRagC: 35793"
  },
  {
    "caption": "(b) dRagA and dRagC are not required for dAkt phosphorylation. Drosophila S2 cells untreated (lanes 1-3) or treated with the indicated RNAi were starved of amino acids for 1 h and stimulated with amino acids for 30 min. Phosphorylation and protein levels of dAkt were determined by immunoblotting with appropriate antibodies as indicated. NC, negative control RNAi.",
    "ncbi_link": "dRagA: 41071
dRagC: 35793"
  },
  {
    "caption": "(c) dRagA and dRagC function in parallel with TSC2 and PTEN. dRagA and/or dRagC RNAi was added to S2 cells in combination with dTSC2 or dPTEN RNAi, as indicated. dTSC2 or dPTEN RNAi treatment increased pdS6K (Thr 398) and this increase was compromised by dRagA or/and dRagC RNAi. Full scans of blots are provided in Supplementary Information, Fig. S6.",
    "ncbi_link": "dTSC2: 40201
TSC2: 40201
dPTEN: 43991
PTEN: 43991
dRagA: 41071
dRagC: 35793"
  },
  {
    "caption": "(a) Constitutively active RagA and RagB stimulate S6K phosphorylation. 200 ng of each mammalian RagA, RagB, RagC or RagD construct was co-transfected with HA-S6K (20 ng) into HEK293 cells. Their corresponding dominant-negative mutants (RagAT21N, RagBT54N, RagCS75N, RagDS76N) and constitutively active mutants (RagAQ66L, RagBQ99L, RagCQ120L, RagDQ121L) were also tested. Phosphorylation and protein levels were determined by immunoblotting with the appropriate antibodies, as indicated.",
    "ncbi_link": "S6K: 6198
RagA: 10670
RagB: 10325
RagC: 64121
RagD: 58528"
  },
  {
    "caption": "(b) RagA has a dominant role over RagC in regulating S6K phosphorylation. Each Rag construct (200 ng) indicated was co-transfected with HA-S6K (20 ng). The different Rag mutants used in the transfection are indicated at the top of each lane.",
    "ncbi_link": "RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(c) Rag regulates TORC1 but not TORC2 activity. Each indicated Rag construct (200 ng) was co-transfected with either HA-S6K (20 ng), Myc-4EBP1 (20 ng) or of GST-Akt (100 ng). Phosphorylation and protein levels were determined by immunoblotting with the appropriate antibodies, as indicated. Full scans of blots are provided in Supplementary Information, Fig. S6.",
    "ncbi_link": "Akt: 207
4EBP1: 1978"
  },
  {
    "caption": "(a) RagAQ66L and RagCS75N activate TORC1 in the absence of amino acids. Each Rag construct (200 ng) indicated was co-transfected with HA-S6K (20 ng) into HEK293 cells. Cells were starved of amino acids for 1 h before collection. Phosphorylation and protein levels were determined by immunoblotting with the appropriate antibodies, as indicated.",
    "ncbi_link": "RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(b) RagAT21N and RagCQ120L block S6K phosphorylation in response to amino acid (AA) stimulation. pcDNA3 (200 ng, lanes 1 and 2) or each indicated Rag construct was co-transfected with HA-S6K into HEK293 cells. Cells were starved of amino acids for 1 h (-AA) and either remained in the starvation medium or were stimulated with amino-acid-containing-medium (+AA) for 30 min before collection. Phosphorylation and protein levels were determined by immunoblotting with the appropriate antibodies, as indicated.",
    "ncbi_link": "S6K: 
RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(c) RagAT21N and RagCQ120L suppress insulin-induced stimulation of S6K phosphorylation. pcDNA3 (200 ng, lanes 1 and 2) or each indicated Rag construct was co-transfected with HA-S6K (20 ng) or GST-Akt (100 ng) into HeLa cells. Cells were serum-starved overnight and stimulated with insulin (400 nM) for 30 min. Phosphorylation and protein levels were determined by immunoblotting with the appropriate antibodies, as indicated. Full scans of blots are provided in Supplementary Information, Fig. S6.",
    "ncbi_link": "Akt: 207
S6K: 6198
RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(a) dRagA positively regulates wing compartment size. Wild-type or mutant dRagA transgenes were expressed in posterior compartments with the en-GAL4 driver. The ratios of representative posterior to anterior compartment areas are shown. Posterior compartment area was significantly increased in response to dRagAQ61L expression and decreased in response to dRagAT61N expression. Data are mean ± s.d., *P = 7.32 × 10−4 (n = 7), **P = 6.18 × 10−4 (n = 12), Student's two-tailed t-test, (n is the number of adult wings analysed).",
    "ncbi_link": "GAL4: 
dRagA: 41071"
  },
  {
    "caption": "(b) dRagA positively regulates wing cell size. The average area of posterior compartment cells from en-GAL4 UAS-dRagA adult wings is shown. Cells expressing dRagAQ61L are significantly larger and dRagAT61N-expressing cells are smaller than controls. Data are mean ± s.d., *P = 1.15 × 10−3 (n = 7), **P = 0.025 (n = 12), Student's 2-tailed t-test (n represents number of adult wings analysed).",
    "ncbi_link": "GAL4: 
dRagA: 41071"
  },
  {
    "caption": "(c, d) dRag GTPases positively regulate larval fat body cell size. (c) Cell area of clonally-induced dRagA-expressing cells or dRagC homozygous mutant cells relative to neighbouring wild-type control cells is shown. Cell area was determined from phalloidin-stained fixed fat body samples from fed or 48 h starved larvae. Expression of dRagAWT or dRagAQ61L significantly increased relative cell area under starvation but not fed conditions. Cells expressing dRagAT61N and dRagC loss-of-function cells were significantly smaller than control cells only under nutrient replete conditions. Data are means ± s.d., *P = 2.04 × 10−3 (n = 5), **P = 2.94 × 10−6 (n = 14), ***P = 3.79 × 10−7 (n = 14), ****P = 1.36 × 10−5 (n = 30), Student's two-tailed t-test. (d) Representative examples of fat body cells with altered dRagA activity. Cells expressing dRagA transgenes are marked by the expression of GFP in the left and middle panels, and dRagC homozygous mutant cells are marked by absence of GFP in the right panel. Scale bar represents 50 μm.",
    "ncbi_link": "dRagA: 41071
dRagC: 35793"
  },
  {
    "caption": "(a) Rag acts through TORC1 to regulate S6K phosphorylation. HEK293 cells were transfected with constructs as indicated. Co-expression of of mTORKD construct (600 ng) or rapamycin treatment (rapa, 20 nM, 30 min) abolished the effect of RagAQ66L and RagCS75N on S6K phosphorylation. The protein level of mTORKD was determined by immunoblotting with anti-mTOR antibody.",
    "ncbi_link": "mTOR: 2475
S6K: 6198
RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(b) RagA/RagC and TSC1/TSC2 independently regulate S6K phosphorylation. HEK293 cells were transfected with 200 ng of each Rag and/or ′ constructs as indicated. Amino acid starvation for 1 h (-AA) is indicated. Phosphorylation and protein levels of the transfected proteins were determined by immunoblotting with appropriate antibodies, as indicated.",
    "ncbi_link": "RagA: 10670
RagC: 64121
TSC1: 7248
TSC2: 7249"
  },
  {
    "caption": "(c) TSC2 and RagA/B independently affect S6K phosphorylation. HA-S6K (20 ng) was transfected into HeLa cells with or without RNAi against human TSC2, RagA and RagB as indicated.",
    "ncbi_link": "S6K: 
RagA: 10670
RagB: 10325
TSC2: 7249"
  },
  {
    "caption": "(d) RagAT21N and RagCQ120L do not block Rheb-induced S6K phosphorylation. RagAT21N and RagCQ120L (200 ng each) were transfected into HEK293 cells with or without Rheb construct (20 ng). S6K was included in the co-transfection. Phosphorylation and protein levels of the transfected proteins were determined by immunoblotting with appropriate antibodies, as indicated. Full scans of blots are provided in Supplementary Information, Fig. S6.",
    "ncbi_link": "Rheb: 6009
RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(a, b) dRagC is not required for Rheb-induced cell growth. (a) The area of Rheb-overexpressing cells in control or dRagC mutant (dRagC−/−) backgrounds under fed conditions, relative to that of neighbouring control cells which were assigned a value of 1. Overexpression of Rheb led to a significant increase in cell area in both control and dRagC mutant backgrounds. Data are mean ± s.d., *P = 0.034 (n = 5), **P = 6.1 × 10−3 (n = 5), Student's two-tailed t-test (n represents number of experimental samples). (b) A representative example of a clone of Rheb-overexpressing cells in a dRagC−/− animal. Rheb transgene-expressing cells are marked by co-expression of GFP. Cell boundaries are labelled by phalloidin staining in red; nuclei are labelled by DAPI in blue. Scale bar represents 50 μm.",
    "ncbi_link": "dRagC: 35793
Rheb: 117332"
  },
  {
    "caption": "(c, d) Expression of dRagAQ61L fails to rescue the growth impairment of Rheb mutant cells. (c) Relative area of clonally-induced Rheb26.2 homozygous mutant cells in a control background and in animals expressing dRagAQ61L throughout the fat body. Clonally induced Rheb26.2 homozygous mutant cells were significantly smaller than neighbouring control cells both in wild-type and in dRagAQ61L expressing backgrounds. Data are mean ±s.d., *P = 2.91 × 10−4 (n = 7), **P = 2.59 × 10−8 (n = 5), Student's two-tailed t-test (fed conditions where n represents number of experimental samples). (d) A representative example of Rheb homozygous mutant cells (marked by lack of GFP, arrows) in fat body ubiquitously expressing UAS-dRagAQ61L. GFP-positive control cells in this experiment are a mixture of Rheb+/− and Rheb+/+. Scale bar represents 50 μm.",
    "ncbi_link": "Rheb: 117332
Rheb: Q9VND8///117332"
  },
  {
    "caption": "(a-d) dRagAQ61L suppresses autophagy. (a) Drosophila fat body cells clonally expressing dRagAQ61L (marked in green by GFP expression) failed to accumulate autolysosomes (shown in surrounding control cells by punctate Lysotracker Red staining) in response to starvation for 4 h. Nuclei are marked in blue by DAPI. (b-d) Induction of autophagosomes in response to 4-h starvation is shown by the punctate pattern of GFP-Atg8a expression in control fat body cells (b), but not in cells expressing dRagAQ61L (c). The average number of GFP-Atg8a-marked autophagosomes per cell in control and dRagAQ61L-expressing clones is shown (d). Data are mean ± s.d., *P = 2.91 × 10−6, Students two-tailed t-test (n = 33 fat body samples imaged per genotype). Scale bars represent 25 μm in each panel.",
    "ncbi_link": "dRagA: 41071"
  },
  {
    "caption": "(e) RagA regulates LC3 conversion in mammalian cells. Myc-LC3 was co-transfected with RagAQL and RagCSN or RagATN and RagCQL into HEK293 cells as indicated. One day after transfection, cells were cultured in amino-acid-sufficienct medium (+AA) or amino-acid-depleted medium (−AA) for 4 h before collection. Western blotting for Myc-LC3 and HA-Rag were performed. Autophagic conversion of LC3I into the lipidated LC3II form was blocked by active RagA and stimulated by dominant-negative RagA. Full scans of blots are provided in Supplementary Information, Fig. S6.",
    "ncbi_link": "LC3: Q9GZQ8///Q9BXW4///Q9H492///440738///81631///84557
LC3: 440738///81631///84557
RagA: 10670
RagC: 64121"
  },
  {
    "caption": "(a, b) dRagA activation increases sensitivity to starvation. Expression of dRagAQ61L using the fat-body-specific Cg-GAL4 driver significantly decreased survival of adult female flies under starvation (b) but not fed (a) conditions, relative to controls (Cg-GAL4 alone). Asterisks indicate significant difference, compared with controls. Data are mean ± s.d., *P 0.05, Students two-tailed t-test (n = 150 flies/genotype/treatment).",
    "ncbi_link": "GAL4: 
Cg: 36571
dRagA: 41071"
  },
  {
    "caption": "Control Western blot of HEK293 protein lysates obtained from cells transfected with mCherry (lane 1) or CASPR1-mCherry cDNA (lane 2) and probed with anti-mCherry antibody",
    "ncbi_link": "mCherry: 
CASPR1: 8506"
  },
  {
    "caption": "LDH release and IL-1β secretion from unprimed wild-type and Gbp2−/− BMDMs infected for 16h with the indicated bacteria (grown to stationary phase). Graphs show mean and s.d. of quadruplicate wells and data are representative of two (b) and three (a, c-f) independent experiments. *Crossreactive band; **P<0.01; NS, not significant (two-tailed t-test).",
    "ncbi_link": "Gbp2: 14469"
  },
  {
    "caption": "b. d-g, LDH release and immunoblots for caspase-1 and caspase-11 from BMDMs infected for 16 h or transfected with LPS in presence or absence of 3-methyladenine (3-MA).",
    "ncbi_link": "caspase-11: 12363"
  },
  {
    "caption": "e-h, Quantification of cytosolic and vacuolar bacteria by flow cytometry in BMDMs infected with mCherry-positive S. typhimurium (e-g) or S. flexneri (h, wild-type or ΔT3SS) for 4 h. Graphs show mean and s.d. or 5-95 percentile (Box plots) of technical triplicates. Data are representative of 2 (g, h), 3 (a-d) and 4 (e, f) independent experiments. *P  0.05, **P  0.01 (two-tailed t-test).",
    "ncbi_link": "T3SS: "
  },
  {
    "caption": "HTT was knocked down in HdhQ7 or HdhQ111 cells by lentiviral infection. The protein levels of HSF1 were detected in mitochondrial fractions. (n=3 biological replicates).",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "HdhQ7 cells were transfected with Flag-mtHSF1 and stained with anti-Tom20 (green) and anti-Flag (red) antibodies. Mitochondrial morphology was examined by confocal microscopy. Scatterplot with bar showed the percentage of cells with mitochondrial fragmentation. The scale bar represents 40 µm. (n=3 biological replicates, at least 100 cells per group were counted).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "The total protein levels of p-Drp1 S616, p-Drp1S637, Drp1, OPA1, MFN2, Flag-mtHSF1 and actin (loading control) were determined by WB analysis. (n=3 biological replicates).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "Mitochondrial morphology was analyzed by electron microscopy (EM) in mice injected with AAV-Con or AAV-mtHSF1. Scatterplot showed the length of mitochondria. The scale bar presents 4 µm, and the enlarged image scale bar is 400 nm. (n=3 mice/group). AAV-Con group, n=268 mitochondria were measured; AAV-Flag-mtHSF1 group, n=179 mitochondria were measured.",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "The mtDNA content was examined with primers of D-loop, mtCO1, mtCO2 and mtND2 by qPCR in control or Flag-mtHSF1-expressing striatal cells. Scatterplot with bar showed the relative percentage of mtDNA content. (n=3 biological replicates).",
    "ncbi_link": "Flag: 
mtCO1: 4512
mtCO2: 4513
HSF1: 3297
mtND2: 4536"
  },
  {
    "caption": "qPCR analysis of the mtDNA content of AAV-Con-injected mice or AAV-mtHSF1-injected mice. Scatterplot with bar showed the relative percentage of mtDNA content (n=3 mice/group).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "Cleaved-Caspase3 in AAV-Con- or AAV-mtHSF1-injected mice was detected by WB analysis. (n=5 mice/group).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "Representative images and scatterplot showing the number of mtDNA (purple) colocalized with mitochondria (Tom20, green) in striatal organoids injected with AAV-Con or AAV-mtHSF1. The data were obtained from 3 independent biological experiments. Con: n=65 cells from 20 organoids; Flag-mtHSF1: n=70 cells from 20 organoids. Two-tailed unpaired t-test was used. Images were captured by Structured Illumination Microscopy (SIM).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "The typical nuclear fragmentation morphology of AAV-Con- (GFP) or AAV-mtHSF1-injected striatal organoids was measured. Scatterplot showed the quantitative result of nuclear fragmentation. The arrows (yellow) mark fragmented nuclei. Two-tailed unpaired t-test was used. The data were obtained from 3 independent biological experiments. Con: n=14 organoids; Flag-mtHSF1: n=15 organoids.",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "Cells were transfected with an empty vector or Flag-mtHSF1 for 48 h. The total cell lysates were harvested and crosslinked with DSS. SSBP1 oligomers were tested by immunoblotting. (n=4 biological replicates).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "Flag-mtHSF1 was expressed in the striata of WT mice for three weeks. SSBP1 oligomers were determined by immunoblotting. (n=5 mice/group).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "Flag-mtHSF1 or sh-SSBP1 was delivered into cells via lentiviral infection. The expression of SSBP1 and mtHSF1 was detected by WB analysis. The mtDNA content was examined by qPCR analysis. (n=3 biological replicates).",
    "ncbi_link": "Flag: 
HSF1: 3297
SSBP1: 381760"
  },
  {
    "caption": "Primary neurons expressing Flag-mtHSF1 were stained with anti-DARPP32 (green) and anti-Flag (red) antibodies. The arrows (white) mark Flag+ or Flag- primary neurons. The neurite length of Flag+ or Flag- neurons was measured by Image J and showed by scatterplot. The scale bar represents 50 µm. (n = 155 for Flag- group and n = 154 for Flag+ group).",
    "ncbi_link": "Flag: 
HSF1: 3297"
  },
  {
    "caption": "Human striatal organoids were injected with AAV-Con (GFP) or AAV-mtHSF1 at D42. Scatterplot showed the percentage of NeuN+ cells (red) among Flag+ or GFP+ cells (green) after injection for 2 weeks. The data were obtained from 3 independent biological experiments. Con: n=11 organoids; Flag-mtHSF1: n=13 organoids. The scale bar represents 100 µm.",
    "ncbi_link": "GFP: 
HSF1: 3297"
  },
  {
    "caption": "The striatum of AAV-Con- or AAV-mtHSF1-injected mice were harvested. The DARPP32 protein levels were tested by WB analysis. (n=6 mice/group).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "Mitochondrial fractions were isolated from WT or Drp1-KO MEFs. The protein levels of Drp1 and HSF1 were tested by immunoblotting. (n=3 biological replicates).",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": "(B) Genome browser representation of the SOX2 locus. The promoter is defined as the unmethylated region spanning the SOX2 transcriptional start site in MCF7-control.",
    "ncbi_link": "SOX2: 6657"
  },
  {
    "caption": "Genomic distribution of (C) identified ZF-D3A binding sites, and (D) differentially methyl- ated regions (DMRs) between MCF7-control and ZF-D3A +dox.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(E) Shown for all DMRs identified between ZF-D3A +dox and MCF7-control is: ∆mCG (difference in the methylation level [ratio of C base calls to total base calls for all CG dinucleotides in region, mCG/CG] between ZF-D3A +dox and MCF7-control), ZF-D3A ChIP-seq signal (normalized ChIP-seq read density, ±1kb flanking DMR center), CpG dinucleotide density (CpG/100bp, ±1kb flanking DMR center), and classification of each DMR as promoter or non-promoter located.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(F) DNA methylation level in MCF7-control and ZF-D3A +dox cells flanking (±1 kb, 100 bp bins) the center of ZF-D3A ChIP-seq peaks identified in ZF-D3A +dox.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(A) Line histogram of DMR methylation levels in each sample. Kernel density estimate smoothed scatterplot comparison of DMR methylation levels in MCF7-control and (B) ZF-D3A +dox, or (C) ZF-D3A dox-wd.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(D) Line histogram of UMR methylation levels in each sample. Scatterplot compari- son of UMR methylation levels in MCF7-control and (E) ZF-D3A +dox, or (F) ZF-D3A dox-wd.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(B) H3K4me3 ChIP-seq normalized read counts in DMRs with ∆mCG >0.2, from H3K4me3 ChIP-seq in ZF-D3A no-dox and ZF-D3A +dox cells. Black line represents equal normalized read counts in ZF-D3A no-dox and ZF-D3A +dox cells; blue line represents a linear regression of the data.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(C) Comparison of UMR ∆mCG and difference in H3K4me3 ChIP-seq normalized read counts between ZF-D3A no-dox and ZF-D3A +dox. Blue line represents a linear regression of the data.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(D) DNA methylation levels of UMRs that intersect with H3K4me3 ChIP-seq peaks in ZF-D3A no-dox and ZF-D3A +dox cells, for genomic DNA or DNA immunoprecipitated with an anti-H3K4me3 antibody.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(E) DNA methylation levels of UMRs that intersect with phos- pho-ser5 RNA polymerase II ChIP-seq peaks in ZF-D3A no-dox and ZF-D3A +dox cells, for genomic DNA or DNA immunoprecipitated with an anti-phospho-ser5 RNA polymerase II antibody.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(B) Box and whisker plots of the DNA methylation levels of the 121 CpG sites in the DACH1 promoter region through- out doxycycline induction and withdrawal. Whiskers indicate 1.5 times the interquartile range or the most extreme data point, whichever is lower.",
    "ncbi_link": "DACH1: 1602"
  },
  {
    "caption": "(C) Average DNA methylation level at the 121 CpG sites in the DACH1 promoter region throughout doxycycline induction followed by doxycycline withdrawal and cell cycle inhibition by growth in doxycycline-free media containing different cell cycle inhibitors (Lovastatin, RO-3306, thymidine).",
    "ncbi_link": "DACH1: 1602"
  },
  {
    "caption": "(D) DMR mCG and hmCG levels in MCF7-control and ZF-D3A +dox cells, ordered by the difference in DMR hmCG level (hmCG/CG) between MCF7-control and ZF-D3A +dox cells, and heatmap representation of H3K4me3 levels in ZF-D3A +dox cells flanking (±2.5 kb, 50 bp bins) the centre of the DMRs.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(A) Scatter plot of the difference in UMR DNA methylation levels, versus the fold change in mRNA abun- dance of UMR-associated expressed genes, between MCF7-control and ZF-D3A +dox. Point color indicates the gene differential expression significance: red indicates FDR <0.01, black indicates FDR >0.01. Trend line (green) was fitted using a generalized additive model, and contour lines represent the relative density of UMRs.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(B) Distribution of the ratios of mRNA levels between ZF-D3A +dox and MCF7-control, for expressed genes that have an associated UMR with a ∆mCG >0.3. Column color indicates the class of mRNA abundance ratios between ZF-D3A +dox and MCF7-control: blue = no decrease; green = small decrease; red = decrease.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "(C) Representative genes with high induction of promoter DNA methylation in ZF-D3A +dox and no reduction in mRNA abundance.",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "Fluorescence distribution of cells stained with RNA-FISH probes targeting (A) GAPDH or (B) PSME1 mRNA before and after FACS.",
    "ncbi_link": "GAPDH: 2597
PSME1: 5720"
  },
  {
    "caption": "mRNA quantitation after FACS sorting of (C) GAPDH by RT-qPCR, and (D) PSME1 by RNA-seq.",
    "ncbi_link": "GAPDH: 2597
PSME1: 5720"
  },
  {
    "caption": "DNA methylation levels of single CpGs at the promoter region of (E) GAPDH, and (F) PSME1, for the low (x axis) and high (y axis) expressing sorted cell populations.",
    "ncbi_link": "GAPDH: 2597
PSME1: 5720"
  },
  {
    "caption": "(G) Genome browser representation of the GAPDH (top) and PSME1 (bottom) promoter regions showing DNA methylation in MCF7-control and low and high expressing sorted cell populations.",
    "ncbi_link": "GAPDH: 2597
PSME1: 5720"
  },
  {
    "caption": "(H) Distribution of per-read methylation levels (blue line) for selected ZF-D3A +dox WGBS reads (≥10 cytosines in the CpG context) that align within robustly methylated DMRs (DMR mean methylation level [mCG/CG] of 0.4-0.6 in ZF-D3A +dox and <0.1 in MCF7-control), and average CG methylation levels from ZF-D3A +dox WGBS data of the DMR genomic intervals covered by the selected reads (red line).",
    "ncbi_link": "D3A: 1788"
  },
  {
    "caption": "HeLa cell lines were treated with the small-molecule Bcl-2/Bcl-XL-inhibitor ABT-737 for 72 h. Cytokines were measured by ELISA. (A) Concentrations of IL-6 were determined (CTRL, n=9; Bax/Bak, n=6; Bcl-XL, n=3; STING, n=3).",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-XL: 598
STING: 340061"
  },
  {
    "caption": "HeLa cell lines were treated with the small-molecule Bcl-2/Bcl-XL-inhibitor ABT-737 for 72 h. Cytokines were measured by ELISA. (B) Concentrations of IL-8 were determined (CTRL, n=7; Bax/Bak, n=4).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "HeLa cell lines were treated with the small-molecule Bcl-2/Bcl-XL-inhibitor ABT-737 for 72 h. Cytokines were measured by ELISA. (C) Concentrations of CXCL1 were determined (CTRL, n=8; Bax/Bak, n=5).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "HeLa cell lines were treated with the small-molecule Bcl-2/Bcl-XL-inhibitor ABT-737 for 72 h. Cytokines were measured by ELISA. (D) Concentrations of FGF-2 were determined (CTRL, n=7; Bax/Bak, n=4).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "HeLa cell lines were treated with the Mcl-1-inhibitor S63845 for 72 h. Cytokines were measured by ELISA. (E) HeLa CTRL cells and Bax/Bak-deficient cells were treated with the Mcl-1-inhibitor S63845. Concentrations of IL-6 in supernatants are shown (CTRL, n=8; Bax/Bak, n=7).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "F 1205Lu human melanoma cells or 1205Lu melanoma cells over-expressing Bcl-XL were treated with ABT-737. Concentrations of IL-6 in the supernatants were measured after 48 h (n=5).",
    "ncbi_link": "Bcl-XL: 598"
  },
  {
    "caption": "G 1205Lu human melanoma cells or 1205Lu melanoma cells over-expressing mouse Bcl-XL were treated with various concentrations of ABT-737. To some aliquots the caspase-inhibitor zVAD-fmk (50 μM) was added. Relative numbers of apoptotic cells were determined as in EV 1B after 48 h. Data are means/SEM of at least three independent experiments. (1205Lu, n=4; 1205Lu 5 µM ABT-737, n=3; 1205Lu/Bcl-XL and 1205Lu + zVAD, n=3).",
    "ncbi_link": "Bcl-XL: 12048"
  },
  {
    "caption": "H HeLa-UL12.5 cells untreated or treated with tamoxifen (100 nM, 24 h) were stained with Picogreen (3 µl/ml) to detect mitochondrial DNA. Scale bare, 10 µm",
    "ncbi_link": "UL12.5: 24271463"
  },
  {
    "caption": "I HeLa CTRL cells and HeLa-UL12.5 cells were treated with ABT-737 (10µM). Concentration of IL-6 in the supernatant were measured after 72h (n=3).",
    "ncbi_link": "UL12.5: 24271463"
  },
  {
    "caption": "(A) HeLa cell lines with an intact (CTRL, carrying a non-coding gRNA) or inactive (Bax/Bak-double deficient) mitochondrial apoptosis apparatus were infected with Chlamydia trachomatis expressing GFP (MOI=0.2). Cells were analyzed by flow cytometry at the indicated time points. Cells were gated on the GFP-positive (infected) host cell population, and mean fluorescence intensity was recorded. Data are means/SEM of six experiments. (A) Growth of C. trachomatis was measured in HeLa cells as increase in GFP-fluorescence between 18 and 38 h. The data show means/SEM of six independent experiments (genotype effect (significance of the difference of GFP-expression between the cell lines overall, p = 0.08). Red line indicates the fold change calculation of the individual different time points and cell lines (significance tested (one sample t-test) for each time point for a difference between Bax/Bak vs CTRL).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "AGS cell lines with an intact (CTRL, carrying a non-coding gRNA) or inactive (Bax/Bak-double deficient) mitochondrial apoptosis apparatus were infected with Chlamydia trachomatis expressing GFP (MOI=0.2). Cells were analyzed by flow cytometry at the indicated time points. Cells were gated on the GFP-positive (infected) host cell population, and mean fluorescence intensity was recorded. Data are means/SEM of 4-5 experiments. (B) Growth of C. trachomatis was measured in AGS cells as increase in GFP-fluorescence. The data show means/SEM of 4 to 5 independent experiments (genotype effect: p<0.0001; time-genotype interaction: p<0.0001) (12 h and 38 h, n=4; 18 h, n=5).",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "D CTRL, Bax/Bak-deficient or Bcl-XL-over-expressing HeLa cells were infected with Salmonella Typhimurium (MOI=50). Extracellular bacteria were killed using non cell-permeable antibiotic. At the indicated time points cells were lysed, and aliquots were plated on agar plates. Recovered colony forming units were calculated. Data are means/SEM of four independent experiments. Significant genotype effects were found between mutant and control cells (Bax/Bak p<0.0001; Bcl-XL p 0.0001).",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-XL: 598"
  },
  {
    "caption": "E CTRL, Bax/Bak-deficient or Apaf-1-deficient HeLa cells were infected with Salmonella Typhimurium (MOI=50). CFU/well were calculated as in (D). n=3.",
    "ncbi_link": "Apaf-1: 317
Bak: 578
Bax: 581"
  },
  {
    "caption": "Western blot  analysis was performed using SETD1A  fragment-expressing 293T  cells. These constructs were used for the following rescue experiments. Representative images from 2 independent experiments are shown.",
    "ncbi_link": "SETD1A: 9739"
  },
  {
    "caption": "Setd1afl/fl;CreER cells were transfected with SETD1A  fragment and endogenous Setd1a  was deleted by tamoxifen, then assayed for colony-forming potential. Representative data from 1 out of 3 independent experiments with 3 biological replicates are shown. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test).",
    "ncbi_link": "Cre: 2777477
ER: 13982
Setd1a: 233904
SETD1A: 9739"
  },
  {
    "caption": "qRT-PCR  was performed at 3 days post-tamoxifen  to analyze Fancd2  expression in human SETD1A-expressing Setd1afl/fl;CreER MLL-AF9 leukemia   cells. qRT-PCR  with 3 biological replicates was performed. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test).",
    "ncbi_link": "Cre: 2777477
ER: 13982
Fancd2: 211651
MLL: 214162
AF9: 70122
SETD1A: 9739
Setd1a: 233904"
  },
  {
    "caption": "293T  cells were transfected with SETD1A-GFP  fusion constructs. Cell nucleus  was visualized with DAPI. The percentage of GFP nuclear localization  is indicated in each image. Asterisks in images indicate the cells with nuclear  specific SETD1A-GFP  signals. Scale bars: 10 µm. G−H. Mouse Setd1afl/fl;CreER MLL-AF9 leukemia  cells were transfected with FO3-GFP  fusion constructs. (G) Subcellular localization  of GFP  fusion constructs was visualized by immunofluorescence  and nucleus  was stained  with DAPI. The percentage of GFP nuclear localization  is indicated in each image. Scale bars: 10 µm. (H) FO3-GFP  fusion expressing cells were treated with tamoxifen  and colony assay with 3 biological replicates was performed. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
Cre: 2777477
ER: 13982
MLL: 214162
AF9: 70122
SETD1A: 9739
Setd1a: 233904"
  },
  {
    "caption": "Relative expression of Mlh1  in SETD1A  rescued MLL-AF9 leukemia  cells. qRT-PCR with 3 biological replicates was performed. Data information: data are presented as mean ± SD. **P ≤ 0.01, *P ≤ 0.05 (Student's t-test for (D)",
    "ncbi_link": "MLL: 214162
AF9: 70122
SETD1A: 9739"
  },
  {
    "caption": "Percentage of GFP+ SETD1A  mutant-expressing leukemia cells in PB  was analyzed at 3 weeks post-transplant (n = 5 / group). Data information: **P ≤ 0.01, *P ≤ 0.05 One-way ANOVA",
    "ncbi_link": "GFP: 
SETD1A: 9739"
  },
  {
    "caption": "Survival  of recipient mice  harboring SETD1A  mutant-expressing  leukemia  cells  after transplantation  (TX) was plotted (n = 5 / group). Data information: **P ≤ 0.01, *P ≤ 0.05  Kaplan-Meier for (F)).",
    "ncbi_link": "SETD1A: 9739"
  },
  {
    "caption": "SETD1A FLOS domain-binding proteins were identified by Co-IP MS. Full-length SETD1A and FO3 fragment were used as baits and overlapped proteins (red dots) were identified as SETD1A FLOS domain-binding proteins.",
    "ncbi_link": "SETD1A: 9739"
  },
  {
    "caption": "293T  cells were transfected with full-length SETD1A   alanine mutants and protein extracts were used for the Co-IP experiments.",
    "ncbi_link": "SETD1A: 9739"
  },
  {
    "caption": "F. MOLM-13 leukemia  cells were examined by  ChIP-seq  analyses against HA-tagged SETD1A, BuGZ, BUB3, H3K4me3 and H3K4me1. Heatmaps of SETD1A(+)/BuGZ(+) regions (upper) and SETD1A(-)/BuGZ(+) regions (lower) are shown.",
    "ncbi_link": "SETD1A: 9739
BuGZ: 7756"
  },
  {
    "caption": "Relative expression  levels of Bugz  were analyzed in Bugz  shRNA-expressing mouse MLL-AF9 leukemia  cells at day 3 post-treatment, respectively. Data from 3 biological replicates are shown. Data information: data are presented as mean ± SD. **P ≤ 0.01 (Student's t-test",
    "ncbi_link": "MLL: 214162
AF9: 70122
Bugz: 22680"
  },
  {
    "caption": "Images are shown of representative karyotypes  in control, Bugz  and Bub3  shRNA-expressing leukemia  cells. Asterisks in images indicate the trisomy 15 in all cells analyzed. Red arrows indicate chromosomal aneuploidies. Representative images of sister-chromatid  separation or aneuploidy  in Bub3  shRNAs are shown in lower panels.",
    "ncbi_link": "Bub3: 12237
Bugz: 22680"
  },
  {
    "caption": "293T  cells were transfected with SETD1A  F2 alanine mutant constructs. Myc-DDK-tagged SETD1A  was used for Co-IP.",
    "ncbi_link": "DDK: 
Myc: 
SETD1A: 9739"
  },
  {
    "caption": "293T  cells were transfected with BuGZ  mutants. Myc-DDK-tagged BuGZ  mutants illustrated on Figure S5B were used for Co-IP.",
    "ncbi_link": "DDK: 
Myc: 
BuGZ: 7756"
  },
  {
    "caption": "293T  cells were transfected with BUB3  mutants and protein extracts were used for the  Co-IP experiments. Myc-DDK-tagged BUB3  mutants illustrated on Figure S5C were used.",
    "ncbi_link": "DDK: 
Myc: 
BUB3: 9184"
  },
  {
    "caption": "293T  cells were transfected with Myc-DDK-tagged human BuGZ  constructs and the protein extracts were used for a Co-IP  experiment.",
    "ncbi_link": "DDK: 
Myc: 
BuGZ: 7756"
  },
  {
    "caption": "293T  cells were transfected with Myc-DDK-tagged BuGZ  variant constructs and the protein extracts were used for the Co-IP  experiment.",
    "ncbi_link": "DDK: 
Myc: 
BuGZ: 7756"
  },
  {
    "caption": "293T  cells were transfected with Myc-DDK-tagged BuGZ  constructs and the protein extracts were used for a Co-IP experiment.",
    "ncbi_link": "DDK: 
Myc: 
BuGZ: 7756"
  },
  {
    "caption": "293T  cells were transfected with Myc-DDK-tagged wild-type BuGZ  and the cells were treated with 1,6-hexanediol for 3 h. The protein extracts were used for the Co-IP experiments.",
    "ncbi_link": "DDK: 
Myc: 
BuGZ: 7756"
  },
  {
    "caption": "SETD1A-GFP  fusion-expressing Setd1afl/fl;CreER MLL-AF9 leukemia cells were treated with tamoxifen, then assayed for  colony-forming potential. The FUCCI reporter (mCherry-Cdt1(30-120)/Citrine-Geminin(1-110))-expressing cells were used as control. Data from 3 biological replicates are shown. Data are presented as mean ± SD.",
    "ncbi_link": "Cdt1: 
Citrine: 
Geminin: 
GFP: 
mCherry: 
Cre: 2777477
ER: 13982
MLL: 214162
AF9: 70122
SETD1A: 9739
Setd1a: 233904"
  },
  {
    "caption": "SGC-expressing Setd1afl/fl;CreER MLL-AF9 leukemia  cells were treated with tamoxifen, and RNA-seq  analysis was performed with sorted cells. Data are shown as log2 fold change over tamoxifen  non-treated GFP-expressing control.",
    "ncbi_link": "GFP: 
Cre: 2777477
ER: 13982
MLL: 214162
AF9: 70122
Setd1a: 233904"
  },
  {
    "caption": " C Heatmap of the significant regulations upon induction of overexpression of the five members of the core network, the activators (green) ERF6, ERF59, ERF98 and the repressors (red) ERF8 and ERF9. Color code represents FDR-corrected p-values with thresholds at FDR=0.01, 0.05 and 0.1. Data information: In A, data are extrapolated from estimated averages, n = 3 independent experiments, FDR-corrected p-values < 0.1 (mixed model analysis, user-defined Wald tests). The thickness of the arrows represents the FDR value. In B, data are presented as averages, n = 3 independent experiments. The intensity of the color of the arrows represents the strength of the regulation according to the TEA values and the thickness the FDR value of the nCounter Nanostring experiment. In C, data are represented as FDR-corrected p-values, n = 3 independent experiments. ",
    "ncbi_link": "ERF6: 827463
ERF8: 841751
ERF9: 834444
ERF59: 844143
ERF98: 821901"
  },
  {
    "caption": "B Average area of the individual leaves of rap2.6L and myb51, two knock-out lines with a smaller average rosette area.",
    "ncbi_link": "myb51: 838438
rap2.6L: 831174"
  },
  {
    "caption": " C The effect of ERF6, ERF9, ERF98 and WRKY15 on the GA2-OX6 promoter determined with transient expression assays. The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Data information: In C, data are presented as mean ± SEM, n = 3 independent experiments.",
    "ncbi_link": "ERF6: 827463
ERF9: 834444
GA2-OX6: 839508
ERF98: 821901
WRKY15: 816864"
  },
  {
    "caption": "B Leaf series of stz and erf11 mutants grown on control and mild osmotic stress conditions.Data information: In B, data are presented as mean ± SEM, n = 3 independent experiments, *=P<0.05 (mixed model, partial F-tests).",
    "ncbi_link": "erf11: 839733
stz: 839666"
  },
  {
    "caption": "A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes ERF11 (A) The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments. ",
    "ncbi_link": "ERF11: 839733"
  },
  {
    "caption": "A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes ERF5 (B) The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments. ",
    "ncbi_link": "ERF5: 834770"
  },
  {
    "caption": "A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes MYB51 (C) The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments. ",
    "ncbi_link": "MYB51: 838438"
  },
  {
    "caption": "A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes, RAP2.6L (D) The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments. ",
    "ncbi_link": "RAP2.6L: 831174"
  },
  {
    "caption": "A, B, C, D, E The effect of the individual and the combination of two TFs on the expression of target genes ERF6 (E). The relative luminescence was calculated relative to the control, 35S::GUS (n = 4 biological repeats). Green represents activation, red repression and gray absence of regulation. Data information: Data are presented as mean ± SEM, n = 3 independent experiments. ",
    "ncbi_link": "ERF6: 827463"
  },
  {
    "caption": "Cells were treated with CTRL, Beclin1 (left) or Atg7 (right) siRNA, then infected for 24 h. Cell mortality (that is, fold change relative to mock‐infected cells) (J), viral replication (K) and production (L) were assessed and whole‐cell lysates of siRNA‐treated cells were immunoblotted for Beclin1, Atg7, capsid and actin (M). Images and graphs shown are representative of at least three independent experiments and data presented in graphs correspond to mean+s.d. (n=3). Scale bar, 10 μm. CHIKV, Chikungunya virus; CTRL, control; GFP, green fluorescent protein; DMSO, dimethylsulphoxide; siRNA, short interfering RNA.",
    "ncbi_link": "Atg7: 10533
Beclin1: 8678"
  },
  {
    "caption": "Cells were treated with CTRL or p62 siRNA, then infected for 24 h. Cell mortality (that is, fold change relative to mock‐infected cells) (F), viral replication (left) and qRT‐PCR (right) (G), and viral production (H) were assessed and whole‐cell lysates were immunoblotted for p62, capsid or actin (I).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Cells were treated with CTRL or NDP52 siRNA, then infected for 24 h. Cell mortality (that is, fold change relative to mock‐infected cells) (J), viral replication (left) and qRT‐PCR (right) (K) and production were assessed (L).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "Whole‐cell lysates of siRNA‐treated cells were immunoblotted for NDP52, capsid or actin (M). Images and graphs shown are representative of at least three independent experiments and data presented in graphs correspond to mean+s.d. (n=3). Scale bar, 10 μm. C, capsid; CHIKV, Chikungunya virus; CTRL, control; NDP52, nuclear dot protein 52 kDa; qRT‐PCR, quantitative reverse transcription polymerase chain reaction; siRNA, short interfering RNA.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "Cells were infected for 3 h and then transfected with empty plasmid (CTRL) or p62WT‐3XFLAG or p62deltaUBA‐3XFLAG. Immunoprecipitation experiments were performed 24 h p.i. with anti‐FLAG antibody. Immunoprecipitated proteins were revealed using antibodies to FLAG or capsid (F).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Cells were treated with CTRL or p62 siRNA, then infected for 24 h. Immunoprecipitation experiments were performed using antibodies to FK2 or nonspecific IgG controls. Immunoprecipitated proteins were revealed using anti‐capsid antibody (G).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Cells were treated with CTRL or p62 siRNA and transfected with NT or capsid‐3XFLAG. Cell mortality (that is, fold change relative to mock‐infected cells) was measured 48 h post transfection (L).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Cells were infected with CHIKV for 3 h and transfected with empty plasmid (CTRL), p62WT‐3XFLAG, p62deltaUBA‐3XFLAG or p62deltaLIR‐3XFLAG. Cell mortality (that is, fold change relative to mock‐infected cells) was measured 24 h post transfection (M).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Human NDP52 binds nsP2, localizes near CHIKV RCs, and restricts cell shutoff promoting cell survival in HeLa cells. Yeast cells expressing Gal4 DNA BD fused alone (empty vector) or to nsP2 were cotransformed with a plasmid encoding the Gal4 AD fused to NDP52 or the indicated NDP52 deletion mutants (top). Yeast cells expressing BD fused to nsP2 or the indicated nsP2 deletion mutants were cotransformed with a plasmid encoding the Gal4 AD fused alone (empty vector) or to NDP52 (bottom) (A).",
    "ncbi_link": "NDP52: 10241
Gal4: 855828
nsP2: 956309"
  },
  {
    "caption": "Cells were treated with control (CTRL) (left) or NDP52 (right) siRNA, infected for 15 h, then labeled using antibodies to NDP52, nsP2 and puromycin. Quantitative analysis was performed by counting the percentage of infected cells with TGN‐associated RCs (n=30 cells per experiment) (D).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "Cells were transfected with empty plasmid (CTRL) or nsP2wt‐3XFLAG or nsP2R606A‐3XFLAG. Cell mortality (that is, % of dead cells) was measured 24 h post transfection (E).",
    "ncbi_link": "nsP2: 956309"
  },
  {
    "caption": "Cells were treated with control (CTRL) or NDP52 siRNA, then mock infected (M) or infected (C) for 24 h. Cytoplasmic and nuclear fractions were isolated and immunoblotted for nsP2 and NDP52. The amounts of the cytoplasmic and nuclear fractions of nsP2 were quantified by densitometry and expressed as the ratio of nuclear to cytoplasmic fraction of nsP2 (F).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "Cells were treated with control (CTRL) or NDP52 siRNA, infected for 15 and 24 h and treated with puromycin. Whole‐cell lysates of siRNA‐treated cells were immunoblotted for NDP52, capsid or actin. Puromycin incorporation into newly synthesized protein was revealed using antibodies to puromycin (G).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "Cells were treated with CTRL or NDP52 siRNA, then transfected with NT or nsP2‐3XFLAG. Cell mortality (that is, fold change relative to mock‐infected cells) was measured 48 h post transfection (H).",
    "ncbi_link": "NDP52: 10241
nsP2: 956309"
  },
  {
    "caption": "NDP52 promotes CHIKV infection in a species‐specific manner. MEF cells were treated with CTRL or NDP52 siRNA, then infected for 24 h. Cell mortality (that is, fold change relative to mock‐infected cells) (A) and viral production (B) were measured. Yeast cells expressing Gal4 DNA BD fused alone (empty vector) or to nsP2 were cotransformed with a plasmid encoding the Gal4 AD fused to hNDP52 or mouse NDP52 (C).",
    "ncbi_link": "NDP52: 10241
NDP52: 76815
Gal4: 855828"
  },
  {
    "caption": "MEF cells were infected for 3 h and transfected with empty plasmid (CTRL) or hNDP52‐3XFLAG. Immunoprecipitation experiments were performed 24 h p.i. using antibodies to FLAG or nonspecific IgG controls. Immunoprecipitated proteins were revealed with anti‐nsP2 antibody (D).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "MEF cells were infected for 3 h and transfected with empty plasmid (CTRL), hNDP52, hLC3‐C or hNDP52 and hLC3‐C. Viral production (E) and cell mortality (F) were assessed 24 h post transfection. Isogenic wt or Atg5−/− MEFs were infected for 24 h and cell mortality (that is, fold change relative to mock‐infected cells) (G) and viral production (H) were assessed. MEF cells were infected and immunoprecipitation experiments were performed 24 h p.i. using antibodies to p62 or nonspecific IgG controls. Immunoprecipitated proteins were revealed with anti‐capsid antibody (I).",
    "ncbi_link": "Atg5: 11793
NDP52: 10241
LC3‐C: 440738"
  },
  {
    "caption": "MEF cells were treated with CTRL or p62 siRNA, then infected for 24 h. Cell mortality (that is, fold change relative to mock‐infected cells) (J) and viral production were assessed. Whole‐cell lysates of siRNA‐treated cells were immunoblotted for p62 or actin (K).",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "Quantitative RT-PCR and immunoblots of the expression of CD38 and SARM1 in DC and age-matched health control fibroblasts. All values are presented as mean ± SD of three replicates in quantitative RT-PCR. Protein levels are normalized to GAPDH, and mean (± SD) quantification values of 4 controls vs 5 DC samples are shown. Student's t test was performed on DC cells vs controls. Irrelevant intervening lanes have been removed for clarity (full blots are available online as Source Data).",
    "ncbi_link": "CD38: 952
SARM1: 23098"
  },
  {
    "caption": "The efficacy of CD38 shRNA (sh-1 and sh-2) was verified by quantitative RT-PCR in DC fibroblasts and by RT-PCR and immunoblots in A549 cells. The relative CD38 mRNA values in the CD38 knockdown cells were normalized to the scrambled shRNA. All values are presented as mean ± SD of three replicates. Student's t test was performed on DC and A549 cells in indicated conditions.",
    "ncbi_link": "CD38: 952"
  },
  {
    "caption": "Intracellular NAD levels in the scramble and CD38 knockdown DC fibroblasts. The CD38 knockdown DC fibroblasts were treated with the PARP1 inhibitor Olaparib (400nM) and the SIRT1 inhibitor EX 527 (1 μM) for 24 hours. Data are representative four replicates. All values are presented as mean ± SD of four replicates. One-way ANOVA was performed on DC cells in indicated conditions.",
    "ncbi_link": "CD38: 952"
  },
  {
    "caption": "immunoblots of the expression of indicated proteins in the scramble and CD38 knockdown DC fibroblasts. The CD38 knockdown DC fibroblasts were treated with the PARP1 inhibitor Olaparib (400nM) and the SIRT1 inhibitor EX 527 (1 μM) for 24 hours. Data are representative four replicates. All values are presented as mean ± SD of four replicates. One-way ANOVA was performed on DC cells in indicated conditions.",
    "ncbi_link": "CD38: 952"
  },
  {
    "caption": "Intracellular NAD levels in brain tissues from 6-month- old G1 and G3 Tert-/- female mice.",
    "ncbi_link": "Tert: 21752"
  },
  {
    "caption": "immunoblots of the expression of NAD consuming related proteins and their activities in brain tissues from 6-month- old G1 and G3 Tert-/- female mice. The CD38 antibody was validated using the CD38-/- mouse brain tissues.",
    "ncbi_link": "CD38: 12494
Tert: 21752"
  },
  {
    "caption": "C Quantification of immunoblots from the indicated proteins in B. Data information: All values are presented as mean ± SD of G1 Tert-/- mouse brain tissues versus G3 Tert-/- mouse brain tissues. n=4 in each group. P values on the basis of Student's t test.",
    "ncbi_link": "Tert: 21752"
  },
  {
    "caption": "D NADase activity in G1 and G3 Tert-/- mouse brain lysate was determined at various time points during the reaction. NADase activity was not detectable in the extracts treated with the CD38 inhibitor, 78c, at a concentration of 50nM.",
    "ncbi_link": "Tert: 21752"
  },
  {
    "caption": "Cellular and mitochondrial ROS in DC and age-matched healthy control cells in the scramble and CD38 knockdown DC cells (D) were measured by flow cytometry from three replicates.",
    "ncbi_link": "CD38: 952"
  },
  {
    "caption": "A PCR amplification efficiency at the telomere in the mock- and FPG-treated DC and age-matched healthy control fibroblasts supplemented with vehicle or 3 mM NR. All values are presented as mean ± SD of three replicates. The relative telomere PCR amplification in each sample was normalized to the 36B4 reference gene.",
    "ncbi_link": "36B4: "
  },
  {
    "caption": "A Cumulative population doubling analysis of the proliferation of representative scramble and CD38 knockdown DC fibroblasts or DC fibroblasts treated with vehicle or 3 mM NR. Each data point is represented as mean ± SD of three replicates.",
    "ncbi_link": "CD38: 952"
  },
  {
    "caption": "(A) Kaplan Meier plot for survival in NeuT;Apln+/+ (n=11) and NeuT;Apln-/- (n=10) mice with mammary cancer after tumor onset. *P=0.0185; Log rank test.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(B) Tumor volumes, followed over time, of control mammary tumor E0771 cells (shRenilla) and Apelin-depleted (shApln) E0771 cells orthotopically-injected into both syngeneic C57BL/6J Apln+/+ and Apln-/- mice (5x105 cells/mouse), respectively. Tumor volumes were determined using calipers and are shown as mean tumor volumes ± S.E.M. Data shown is pooled from 2 independent experiments. Apln+/+;shRenilla (n=18), Apln+/+;shApln (n=17), Apln-/-;shRenilla (n=14), Apln-/-;shApln (n=15); ** P<0.01, *** P<0.001; two-way ANOVA.",
    "ncbi_link": "Apelin: 30878
Apln: 30878"
  },
  {
    "caption": "(C) Mean percentages (± S.E.M.) of CD31+ area in E0771 shRenilla (n=3) or shApln (n=3) mammary tumors, assessed on day 23 post-orthotopic injection into C57BL/6J Apln+/+ or Apln-/- mice, respectively. **P<0.01; t test. (D) Mean percentages (± S.E.M.) of extravasated Dextran in E0771 shRenilla (n=9) or shApln (n=12) mammary tumors, assessed on day 19 post-orthotopic injection into C57BL/6J Apln+/+ or Apln-/- mice, respectively. **P<0.01; t test. Right panel shows representative immunofluorescence of Dextran (red), CD31+ vessels (green), and DAPI (blue). The white arrows indicate regions of Dextran extravasation. Scale bars = 100 μm",
    "ncbi_link": "Apln: 30878"
  },
  {
    "caption": "(E) Mean counts (± S.E.M.) of pimonidazole positive foci, assessed on day 26 post-orthotopic injection of E0771 shRenilla (n=6) or shApln (n=4) into C57BL/6J wild-type mice (5x105 cells/mouse). *P<0.05; t test. Right panels show representative immunohistochemical pimonidazole staining at two different magnifications; Scale bars = 200 μm (upper panels) and 50 μm (lower panels).",
    "ncbi_link": "Apln: 30878"
  },
  {
    "caption": "(F) Mean percentage (± S.E.M.) of tumor-infiltrating immune cells normalized to CD45+. E0771 shRenilla (n=8) or shApln (n=6) were orthotopically injected into C57BL/6J Apln+/+ or Apln-/- mice (5x105 cells/mouse), respectively and tumors were harvested day 25 post-injection. *P<0.05, **P<0.01; t test. All immune cell populations were gated for viable CD45+ cells and then further defined as: CD8 T cells (Thy1.2+, CD8+), CD4 T cells, (Thy1.2+, CD4+), Inflammatory Monocytes (Ly6C+, Cd11b+, Ly6G-), PMN-MDSCs (Ly6G+, Cd11b+), natural killer cells (Thy1.2-, Ly6G-, NK1.1+), natural killer T cells (Thy1.2+, CD4-, CD8-, NK1.1+) and peripheral dendritic cells (Ly6G- ,Ly6C+, Cd11b- , PDAC1+, B220+).",
    "ncbi_link": "Apln: 30878"
  },
  {
    "caption": "(A) Left - Heatmap of RNA-Seq transcriptome analysis of CD31+/CD105+ endothelial cells sorted from tumors established by E0771 shRenilla (n=6) or shApln (n=3) cells orthotopically injected into C57BL/6J Apln+/+ or Apln-/- mice, respectively. Tumors were harvested day 25 post-injection and genes displayed are significantly deregulated at the adjusted p-value cut-off of 0.05. Right - Ingenuity Pathway Analysis for biological processes predicted to be decreased downstream of the differentially expressed genes.",
    "ncbi_link": "Apln: 30878"
  },
  {
    "caption": "(B) Quantification of vessel sprouts (mean values ± S.E.M.) upon VEGF treatment (30ng/mL) of embryoid bodies (EB) derived from murine ES cells (mESCs) with sense integrations in the Apelin gene (Apln STOP) of the splice acceptor described in Appendix Figure S1B or Cre-reverted antisense (Apln GO) sister cells. Apln GO (Day 2 n=6; Day 4 n=40, Day 6 n=54, Day 8 n= 32, Day 10 n=35, Day 11 n=31), Apln STOP (Day 2 n=4; Day 4 n=15, Day 6 n=31, Day 8 n= 28, Day 10 n=32, Day 11 n=37); ** P<0.01, *** P<0.001, two-way ANOVA. Representative brightfield images and automated analysis of vessel sprouts by Definiens software are shown in the bottom panels. Scale bars = 200 μm",
    "ncbi_link": "Apln: 30878
Apelin: 30878
Cre: 2777477"
  },
  {
    "caption": "(C) Differentially expressed genes using RNAseq transcriptome analysis of CD31+ endothelial cells (ECs) sorted from sprouting EBs from Apelin STOP cells stimulated with VEGF (30ng/mL) and DMSO (-Apln) and repaired Apelin GO sister cells stimulated with VEGF and Apelin (1000nM) (+Apln). VEGF target genes and angiogenesis-related genes, predicted by Ingenuity Pathway Analysis (IPA) software, are indicated by bars on the upper axis of the heatmap. GO terms were analyzed by DAVID on-line software.",
    "ncbi_link": "Apelin: 30878
Apln: 30878"
  },
  {
    "caption": "(A) Experimental set up and (right) Kaplan Meier survival plot of NeuT;Apln+/+ and NeuT;Apln-/- mice with mammary cancer, left untreated (control) or treated with the indicate dose of the broad VEGFR blocker sunitinib. NeuT;Apln+/+ Control (n=8), NeuT;Apln-/- Control (n=11), NeuT;Apln+/+ Sunitinib (n=11), NeuT;Apln-/- Sunitinib (n=12); *P<0.05; Log rank test. Mice were sacrificed when the tumor size reached 1cm3, following ethical guidelines. The dotted line indicates 50% of survival.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(B) Percentages (mean ± S.E.M.) of tumor burden in mammary glands of untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, assessed 4 weeks after tumor onset. NeuT;Apln+/+ Control (n=6), NeuT;Apln-/- Control (n=8), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=5); *P<0.05; ***P<0.001; one-way ANOVA. Representative H&E images are shown for each genotype in the right panels. Scale bars = 1000 μm (large panels) and 50 μm (insets).",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(C) Tumor volumes of untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mammary tumors, size-matched at 20-70mm3 and followed over time by MRI analysis; NeuT;Apln+/+ Control (n=7), NeuT;Apln-/- Control (n=5), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=6) mice per group; Lines represent nonlinear fit of tumor growth. Box and arrow indicate the time point used for analysis in panel D. (D) Mitotic counts (mean ± S.E.M.) and representative H&E images of mammary tumors in untreated (control) ­and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, assessed 6 weeks after tumor onset.; NeuT;Apln+/+ Control (n=7), NeuT;Apln-/- Control (n=6), NeuT;Apln+/+ Sunitinib (n=9), NeuT;Apln-/- Sunitinib (n=4) tumors per group; *P<0.05; one-way ANOVA to sunitinib-treated NeuT;Apln-/-. White arrows indicate mitotic figures. Scale bars = 50 μm",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(B) Representative MRI images; Scale bar = 5mm and (C) quantification (mean ± S.E.M.) of relative tumor blood volume (rTBV) over time after NeuT+ mammary tumors were size-matched at 20-70mm3 (0 weeks). Treatments and genotypes are indicated. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=5); **P<0.01, and ***P<0.001 compared to untreated NeuT;Apln+/+ mice and #P<0.05 compared to untreated control NeuT;Apln-/- mice; two-way ANOVA. Of note, in NeuT;Apln+/+ mice, only 2 tumors could be analyzed after 6 weeks as some mice had to be sacrificed due to the large tumor sizes following ethical guidelines. Thus, we did not perform any statistical analysis on the 6 weeks timepoints.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(D) Analysis (mean values ± S.E.M.) of CD31+ area (x104 μm2)/field, number of dilated tumor vessels and percentage of alphaSMA+ area per CD31+ blood vessels in mammary tumors of untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, assessed 6 weeks after mammary tumors were size-matched. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=5), NeuT;Apln-/- Sunitinib (n=4); *P<0.05; **P<0.01; ***P<0.001; one-way ANOVA and Kruskal-Wallis test. (E) Representative immunofluorescence and immunohistochemistry images from Fig. 5D quantification. Dilated blood vessels are marked by a red asterisk. DAPI (blue) is shown as a counterstain to visualize nuclei. Scale bars = 100 μm (upper panels), 50 μm (middel panels) and 20 μm (lower panels).",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(A) Percentages of CA9+ cells adjacent to CD31+ tumor blood vessels in untreated (control) and sunitinib-treated NeuT;Apln+/+ and NeuT;Apln-/- mice, 6 weeks after mammary tumors were size-matched. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=4), NeuT;Apln+/+ Sunitinib (n=4), NeuT;Apln-/- Sunitinib (n=4); 100-200 peri-vascular intra-tumoral regions per group were counted. ***P<0.001; one-way ANOVA. Right panels show representative immunofluorescent images. Areas limited by dotted white lines indicate CA9+ areas. Scale bars = 50 μm.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(B) Representative MRI images; Scale bar = 5mm and (C) quantification (mean ± S.E.M.) of vessel permeability (K2) in NeuT+ mammary tumors followed over time. Treatments and genotypes are indicated. NeuT;Apln+/+ Control (n=4), NeuT;Apln-/- Control (n=5), NeuT;Apln+/+ Sunitinib (n=4), NeuT;Apln-/- Sunitinib (n=5); ***P<0.001, compared to untreated control NeuT;Apln+/+ mice and §P<0.05 compared to sunitinib-treated NeuT;Apln+/+ mice; two-way ANOVA. Of note, in NeuT;Apln+/+ mice, only 2 tumors could be analysed after 6 weeks as some mice had to be sacrificed due to the large tumor sizes following ethical guidelines. Thus we did not perform any statistical analysis on the 6 weeks timepoints.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "(A) Number of metastatic lung foci in untreated (control) and sunitinib-treated (60mg/kg, three times a week from tumor initiation) NeuT;Apln+/+ or NeuT;Apln-/- mice, assessed 6 weeks after mammary tumors were size-matched. Data of individual lung sections and means (black bars) are shown. Right panels show representative H&E images, where black arrows and insets indicate metastatic foci. Scale bars = 1000 μm (large panels) and 50 μm (insets). *P<0.05, **P<0.01; ***P<0.001; Kruskal-Wallis test; n=3 mice per cohort and three sections per lung were analysed.",
    "ncbi_link": "Apln: 30878
Neu: 13866"
  },
  {
    "caption": "A AP and SAP were induced in wild type (WT) and ANGPTL4 -/- mice (n = 15, each group), as described in the material and methods. H&E staining, TUNEL staining for apoptosis, and immunofluorescence staining for ANGPTL4 (red) and amylase (green) were performed in the pancreatic tissues. ANGPTL4 and IL-6 protein expressions were also determined in pancreatic tissues from ANGPTL4 WT and -/- mice by Western blotting. Scale bar represents 100 µm.",
    "ncbi_link": "ANGPTL4: 57875"
  },
  {
    "caption": "C Immunofluorescence staining of TNF-α and IL-6, and the levels of the inflammatory cytokines TGF-β, IFN-γ, and IL-1β in the sera from ANGPTL4 WT and -/- mice (n = 10, each group). Scale bar represents 150 µm",
    "ncbi_link": "ANGPTL4: 57875"
  },
  {
    "caption": "C Immunofluorescent staining of the F4/80 macrophage marker and quantification of macrophage-positive cells in the AP and SAP groups from the ANGPTL4 -/-and WT mice (n = 10). Scale bar represents 150 µm",
    "ncbi_link": "ANGPTL4: 57875"
  },
  {
    "caption": "A Cell morphology and the mRNA levels of inflammatory cytokines, including and TNF-α, IL-6, and IL-1β in mouse primary macrophages treated with LPS and ANGPTL4 (100 ng/ml) using qPCR and RT-PCR, and levels of TGF-β and NO in the LPS- and ANGPTL4-treated primary macrophages (n = 5). Scale bar represents 100 µm",
    "ncbi_link": "IL-1β: 16176
IL-6: 16193
TNF-α: 21926"
  },
  {
    "caption": "B ANGPTL4 and C5a expression levels were measured in bone marrow-derived macrophages from pancreatitis-induced ANGPTL4-/- and WT mice.",
    "ncbi_link": "ANGPTL4: 57875"
  },
  {
    "caption": "E C5a, C5aR, TNF-α, IL-6, and IL-1β mRNA levels were identified by qPCR in mouse macrophages or primary acinar cells after treatment with ANGPTL4 and LPS (100 ng/ml). In the transwell experiment, mouse primary acinar cells were cultured in the lower well and macrophages were incubated in the upper transwell bucket treated with ANGPTL4 (100 ng/ml). Expression of ANGPTL4, C5aR, and C5a was determined in siANGPTL4-treated THP1-derived macrophage after LPS activation.",
    "ncbi_link": "ANGPTL4: 51129
C5aR: 12273
C5a: 15139
IL-1β: 16176
IL-6: 16193
TNF-α: 21926"
  },
  {
    "caption": "B Immunofluorescence staining of C5a in pancreas tissues from ANGPTL4 -/- and WT animals and macrophage depletion/WT models with pancreatitis. Scale bar represents 150 µm. Levels of C5a were measured in serum (n = 7).",
    "ncbi_link": "ANGPTL4: 57875"
  },
  {
    "caption": "d, ratio between the CPD (copy per  droplets, normalized to γ−actin and Hprt reference genes relative expression) of structural [N,  nucleocapsid] and non-structural [IP4:  RdRp,  RNA-dependent RNA polymerase] viral gene expression  determined by digital droplet PCR  (ddPCR) in the nasal turbinates and in the  lungs at 4 dpi. Data information: Horizontal lines indicate medians. The p value is indicated in bold when significant at a 0.05 threshold. Mann-Whitney test M: male hamsters; F: female hamsters. Data were obtained from two independent experiments for each sex.",
    "ncbi_link": "Hprt: 
IP4: 
γ−actin: 101839375
nucleocapsid: 43740575
RdRp: 43740578
RNA-dependent RNA polymerase: 43740578"
  },
  {
    "caption": "E Rate of protein synthesis as measured by the amount of HPG incorporation after 20 mins of differing time intervals (0 - 60 mins) of 5 µM Torin1 for wild type (green) and tor1∆ (yellow). Values are normalised to T = 0 minutes. Exponential one-phase decay non-linear regressions were fitted using the curve fitting function on Prism9. Data aggregated from 3 independent experiments with error bars representing the standard deviations (SD).",
    "ncbi_link": "tor1: 2540473"
  },
  {
    "caption": "B Relative phosphorylation level of the T632 phosphosite identified on Sck1 in the 40-minute time course study. Phosphorylation levels of both wild type (green) and tor1∆ (yellow) are presented relative to the value for wild type cells at T = 0 minutes. Grey dashed line indicates 2-fold threshold.",
    "ncbi_link": "tor1: 2540473"
  },
  {
    "caption": "A, B Phosphosites identified on (A) Tif212 and (B) Erf1 respectively showing 2-fold phosphorylation change within 20 minutes of Torin1 (5 µM) addition. Both wild type (green) and tor1∆ (yellow) phosphorylation values are relative to the starting phosphorylation levels before Torin1 addition in wild type cells (T=0 minutes). Grey dashed lines indicate 2-fold threshold.",
    "ncbi_link": "tor1: 2540473"
  },
  {
    "caption": "E, F Changes in rates of protein synthesis of the tif471_18A mutant compared to the wild type control (tif471+) upon Torin1 (5 µM) treatment. Residual rates of protein synthesis after 60 minutes of Torin1 treatment was 17% for the tif471_18A phosphomutant and 4.6% for the tif471+ control relative to starting levels in the respective strains. The two graphs represent the untransformed (E) and log2 transformed (F) rates respectively. Error bars represent the standard deviation (SD) of data aggregated from 3 independent experiments.",
    "ncbi_link": "tif471: 2542290"
  },
  {
    "caption": "D Distributions of pairwise Ka/Ks (nonsynonymous to synonymous nucleotide substitution rates) ratios between PIWI duplicates in arthropods (n = 17 in Drosophila and n = 37 in others, Mann-Whitney U test, *P<0.05). The center line of the boxplots represents median value, the bounds of the box represent 75th and 25th percentile, and the whiskers represent maximum and minimum value.",
    "ncbi_link": "PIWI: 34521"
  },
  {
    "caption": "A PIWI  genes are present in the locust brain. Rp49 served as a loading control (n=4 biological replicates). Data information: data are presented as mean ± SEM.",
    "ncbi_link": "PIWI: 
Rp49: "
  },
  {
    "caption": "G Food  intake  by dsPiwi1-treated locusts  and dsGFP-treated control  locusts  within 1 h (n=5 biological replicates) , ***P<0.001 (Student's t-test). Data information: All assays were performed on fourth-instar locusts.",
    "ncbi_link": "GFP: 
Piwi1: "
  },
  {
    "caption": "C Representative images of Nile red staining  of lipid droplets in the fat bodies  of dsPiwi1-treated locusts and dsGFP-treated control locusts (n=5 biological replicates). The scale bars represent 50 µm. D Quantification of  lipid droplet staining   in dsPiwi1-treated locusts  and dsGFP-treated control  locusts (n=5 biological replicates). E Data information: All data are presented as the mean ± SEM (Student's t-test, **P<0.01, ***P<0.001, ns: not significant). All assays were performed on four-day-old fourth-instar locusts.",
    "ncbi_link": "GFP: 
Piwi1: "
  },
  {
    "caption": "B  Food intake within 1 h following treatment with candidate genes (dsNPF1-treated, n=4 biological replicates; dsCG10621-treated, n=5 biological replicates; dsMFS3-treated, n=5 biological replicates), the data are shown as the mean ± SEM (Student's t-test, **P<0.01).",
    "ncbi_link": "CG10621: 
MFS3: 
NPF1: "
  },
  {
    "caption": "D, E Representative images (D) and quantification (E) of Nile red staining  of fat body lipid droplets in dsNPF1-treated locusts  and dsGFP-treated controls (n=5 biological replicates). The scale bars represent 50 µm, the data are shown as the mean ± SEM (Student's t-test, **P<0.01).",
    "ncbi_link": "GFP: 
NPF1: "
  },
  {
    "caption": "B mRNA levels of differentially  expressed piRNAs located within the flanking region of the NPF1  gene in dsPiwi1-treated locusts and dsGFP-treated control  locusts (n=5 biological replicates). Data information: The  qPCR data are shown as the mean ± SEM (Student's t-test, *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "NPF1: 
GFP: 
Piwi1: "
  },
  {
    "caption": "C The mRNA expression  of NPF1 was measured by qPCR after a mixture of inhibitors or mimics of piRs-3-I2 and piRs-3-I3 was injected (n=5 biological replicates). Data information: The qPCR  data are shown as the mean ± SEM (Student's t-test, *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "NPF1: 
piRs-3-I2: 
piRs-3-I3: "
  },
  {
    "caption": "E  Body weight  measurement of locusts administered inhibitors (NC, n=25  locusts; Inhibitors- piRs-3-I2+I3, n=23 locusts) and mimics (NC, n=37 locusts; Inhibitors-piRs-3-I2+I3, n=39 locusts) of  piRs-3-I2 and piRs-3-I3. The center line of the boxplots represents median value, the bounds of the box represent 75th and 25th percentile, and the whiskers represent maximum and minimum value.",
    "ncbi_link": "piRs-3-I2 : 
piRs-3-I2: 
piRs-3-I3: "
  },
  {
    "caption": "F  RNA-binding protein  immunoprecipitation assay of piRs-3-I2 and piRs-3-I3 in Piwi1 immunoprecipitates from brain tissue extracts (n=6 biological replicates). Normal mouse IgG was used as a negative control.",
    "ncbi_link": "piRs-3-I2: 
piRs-3-I3: "
  },
  {
    "caption": "A U6 RNA was used as a nuclear RNA control (relative value set to 1 in the nuclear  fraction), and glycine tRNA was used as the cytoplasmic  RNA control (relative value set to 1 in the  cytoplasmic fraction) (n=4 biological replicates), U6 and   tRNA-Gly  was used as an endogenous control.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "B Relative expressions of piRs-3-I2 and piRs-3-I3 determined by qPCR and high-throughput sequencing in the  nucleus (n=3 biological replicates). The brain tissues were homogenized and then divided into two parts of equal volume; one was prepared for high-throughput sequencing  and the other was used for piRNA quantification in nuclear and cytoplasmic fractions after subcellular RNA fractionation. The relative piRNA expression in  nucleus was determined by multiplying the relative nuclear piRNA fraction estimate by  qPCR quantification by the normalized count of piRNA in high-throughput sequencing libraries. Data information: The  qPCR data are shown as the mean ± SEM (Student's t-test, *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "piRs-3-I2: 
piRs-3-I3: "
  },
  {
    "caption": "C  Expression level of pre-NPF1 in the nucleus after a mixture of inhibitors (piRs-3-I2  and piRs-3-I3) was injected (n=4 biological replicates). D qPCR expression analyses of  pre-NPF1. The precursor mRNA expression  level was measured by  qPCR  after the dsPiwi1 treatments (n=6 biological replicates). E Data information: The qPCR data are shown as the mean ± SEM (Student's t-test, *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "pre-NPF1: 
piRs-3-I2: 
piRs-3-I3: 
Piwi1: "
  },
  {
    "caption": "F Analysis was performed to amplify  pre-NPF1 and piRs-3-I3 in hnRNP F/H  immunoprecipitates from extracts of brain tissue treated with  piRs-3-I3 mimics compared to the negative controls (pre-NPF1  n=3 biological replicates; piRs-3-I3  n=4 biological replicates). G Analysis was performed to amplify pre-NPF1 in U2AF65 immunoprecipitates from extracts of brain tissue treated with  piRs-3-I3  mimics compared to the negative controls (pre-NPF1 n=3 biological replicates). H",
    "ncbi_link": "pre-NPF1: 
piRs-3-I3: "
  },
  {
    "caption": "J Expression level of the mature  NPF1 gene and pre-NPF1 in 293T  cells transfected with pre-NPF1 and mutated pre-NPF1 (n=5 biological replicates). NC means negative control. The center line of the boxplots represents median value, the bounds of the box represent 75th and 25th percentile, and the whiskers represent maximum and minimum value. Data information: The qPCR  data are shown as the mean ± SEM (Student's t-test, *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "NPF1: 
pre-NPF1: "
  },
  {
    "caption": "ChEP analysis using EGFP (control)- or Piwi-KD OSCs. Signals with an adjusted p-value (Bonferroni test) of less than 0.05 are highlighted in red. The signals for Lam, LamC, and H1 are labelled within the plots.",
    "ncbi_link": "EGFP: 
Piwi: 34521"
  },
  {
    "caption": "Lam- or LamC-KD followed by qRT-PCR of RNA levels for piRNA target (mdg1 and gypsy) or non-target (roo) TEs. Error bars indicate SD (n=3). * = p-value<0.05 (t-test). Note that the complete depletion of Lam and LamC is impossible since their KD causes severe damage to cells.",
    "ncbi_link": "mdg1: 
roo: 
Lam: 33782
LamC: 36615
gypsy: 41740"
  },
  {
    "caption": "Boxplots showing fold changes in the expression of piRNA target or non-target TEs based on RNA-seq upon Piwi-KD (left), and the frequency of piRNAs, which target piRNA target TEs or non-piRNA target TEs (right). Definition of piRNA target and non-target TEs is in Fig EV1E. Boxplot whiskers, box, and central band show maximum, third quartile, median, first quartile, and minimum, respectively (n=10 for piRNA target TEs, n= 80 for non-piRNA target TEs). P-values were calculated using the Wilcoxon rank-sum test.",
    "ncbi_link": "Piwi: 34521"
  },
  {
    "caption": "Boxplot showing DamID-seq signals of piRNA target or non-target TEs upon EGFP (control)- or Piwi-KD. Boxplot whiskers, box, and central band show maximum, third quartile, median, first quartile, and minimum, respectively (n=10 for piRNA target TEs, n= 80 for non-piRNA target TEs). P-values were calculated using the Wilcoxon rank-sum test.",
    "ncbi_link": "EGFP: 
Piwi: 34521"
  },
  {
    "caption": "Oligo-FISH images for the representative piRNA target region described in Fig 4A, upon EGFP (control)- or Piwi-KD. Gray indicates DAPI staining for DNA, magenta indicates FISH signal, and green indicates Lamin immunofluorescence staining. Scale bar, 5μm. Ratio of distance from FISH signal to the nuclear periphery (DAPI surface) is quantified at right, dot in the box plot indicates mean value; Boxplot whiskers, box, and central band show minimum, first quartile, median, third quartile, and maximum, respectively. P-values calculated with Mann-Whitney U test.",
    "ncbi_link": "EGFP: 
Piwi: 34521"
  },
  {
    "caption": "Oligo-FISH images for changes in the intra-TAD interaction at the TAD described in (C), upon EGFP (control)- or Piwi-KD. Gray indicates DAPI staining for DNA, green and magenta indicates FISH signal at the different positions of TADs (TAD-1 and TAD-2). Details of TAD probe design is described in Fig EV2C. Scale bar, 5μm. Distance between two FISH signals is quantified at right, dot in the box plot indicates mean value; Boxplot whiskers, box, and central band show minimum, first quartile, median, third quartile, and maximum, respectively. P-values calculated with Mann-Whitney U test.",
    "ncbi_link": "EGFP: 
Piwi: 34521"
  },
  {
    "caption": "Boxplots showing fold changes in the histone mark association of piRNA target or non-target TEs based on ChIP-seq upon Piwi-KD (Definition of piRNA target and non-target TEs are described in Fig EV1E). Boxplot whiskers, box, and central band show maximum, third quartile, median, first quartile, and minimum, respectively (n=10 for piRNA target TEs, n= 80 for non-piRNA target TEs). P-values were calculated by Wilcoxon rank-sum test.",
    "ncbi_link": "Piwi: 34521"
  },
  {
    "caption": "ChIP‐qPCR analysis of H3K27Ac and H3K4me3 occupancy on the reporter gene upon transfection of λN-Nxf2 expression vector or control EGFP expression vector. Bar graph shows the occupancy relative to that of the sample transfected with a control plasmid. Error bars indicate SD (n = 3), * = p-value<0.01 (t-test)..",
    "ncbi_link": "EGFP: 
Nxf2: 39843"
  },
  {
    "caption": "Density plots for DamID-seq signals over consensus sequences from piRNA target (gypsy and mdg1, orange) and non-target TEs (roo, blue) in EGFP (control)- or Nxf2-KD cells.",
    "ncbi_link": "EGFP: 
mdg1: 
roo: 
Nxf2: 39843
gypsy: 41740"
  },
  {
    "caption": "Oligo-FISH images for the reporter of the tethering system, at 0h (control), 48h hours, 96 hours after transfection of λN-Nxf2 expression vector. Gray indicates DAPI staining for DNA, magenta indicates FISH signal, and green indicates Lamin staining. Scale bar, 5μm. The ratio of distance from FISH signal to the nuclear periphery (DAPI surface) is quantified at right, dot in the box plot indicates mean value; Boxplot whiskers, box, and central band show minimum, first quartile, median, third quartile, and maximum, respectively. P-values calculated with Mann-Whitney U test.",
    "ncbi_link": "Nxf2: 39843"
  },
  {
    "caption": "Dot plot showing the correlation between the normalized density of indicated TEs per TAD (x-axis) and changes in intra-TAD interactions upon H1(left)-, Egg(middle)-, or HP1a(right)-KD (y-axis). Trend lines are in red. Spearman's rank correlation rho is indicated along with the p-value (algorithm AS 89). n.s.; not significant (p > 0.05) Dot plot showing the correlation between the normalized density of indicated TEs per TAD (x-axis) and changes in inter-TAD interactions upon H1(left)-, Egg(middle)-, or HP1a(right)-KD (y-axis). Trend lines are in red. Spearman's rank correlation rho is indicated along with the p-value (algorithm AS 89). n.s.; not significant (p > 0.05)",
    "ncbi_link": "Egg: 37962
H1: 3772225
HP1a: 34119"
  },
  {
    "caption": "(B) real time qPCR from brain lysates showing higher PTX3 expression in late embryonic and early postnatal brain, and lower in the adult brain. Data are presented as mean±SEM (B) qPCR fold change normalized on E15, E15=1.037±0.154, P0=0.711±0.094, P7=0.472±0.0524, P14=0.135±0.007, P28=0.168±0.020, P90=0.183±0.029. One-way ANOVA analysis of variance followed by post hoc Tukey test: E15 vs P7 ***p=0.0001, E15 vs P14 **** p<0.0001, E15 vs P2 ****p<0.0001, E15 vs P90 ****p<0.0001; P0 vs P14 $$$p=0.0007, P0 vs P28 $$p=0.001, P0 vs P90 $$p=0.002; 4 animals for each time point",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "Quantitation of PTX3 levels in pure astrocyte and neuronal cultures (D) rea time qPCR performed on astrocyte and neuronal lysates qPCR astro=1.167±0.288; neu=0.148±0.057; Mann-Whitney test **p=0.0095. 2 independent neuronal cultures evaluated. Data are presented as mean±SEM",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "H) Representative images showing 14DIV WT and TSG6 KO neurons stained for surface AMPARs (GluA, green), the presynaptic protein Bassoon (blue) and tubulin (red) in the different tested conditions. Arrowheads point to postsynaptic GluA clusters. Scale bar: 5µm",
    "ncbi_link": "TSG6: 84397"
  },
  {
    "caption": "I) Synaptic surface GluA quantitation showing no effect of PTX3 treatment in TSG6 KO cultures. On the contrary WT cultures (from littermates) display increased surface GluA&Bsn/Bsn upon PTX3 treatment. A significant enhancement of surface GluA receptors was induced by TTX in both TSG6 KO and WT cultures (WT=1±0.06; WT+PTX3=1.389±0.113; WT+TTX=1.698±0.109; Number of fields examined: 40, 39, 32 respectively; Kruskall-Wallis test p<0.0001 followed by post hoc Dunn"s test. TSG6 KO=1.000±0.047; TSG6 KO+PTX3=0.979±0.048; TSG6 KO+TTX=1.363±0.077. Number of fields examined: 54, 57, 29 respectively; one-way ANOVA analysis of variance, p<0.0001 followed by post hoc Tukey test as indicated in figure. n=3 independent experiments, data are presented as normalized mean values",
    "ncbi_link": "TSG6: 84397"
  },
  {
    "caption": "J) Representative mEPSC traces recorded from WT and TSG6 KO littermates cultures treated or not with PTX3 (1μg/ml for 48hrs). K) On the contrary of WT cultures, mEPSC frequency quantitation shows no increase in frequency in TSG6 KO cultures when treated with PTX3(Normalized Frequency, WT Ctr: 1.000±0.074; Wt+PTX3=1.912±0.289; TSG6 KO Ctr=1±0.079; TSG6 KO+PTX3=1.226±0.096; 22, 20, 30, 24 cells respectively, 6 TSG6 KO mice and 4 WT littermates. One way ANOVA test p=0.002 followed by post hoc Dunn's test, data are presented as normalized mean±SEM plus the distribution). L) Cumulative probability plot of mEPSC amplitude and average mEPSC amplitude quantitation (inset) showing no difference in amplitude (WT Ctr: 1.000±0.034, Wt+PTX3=1.069±0.046, TSG6 KO Ctr =1.000±0.028; TSG6 KO+PTX3=1.074±0.67; 22, 20, 30, 24 cells respectively, 6 TSG6 KO mice and 4 WT littermates. One way ANOVA test p=0.817 followed by post hoc Dunn's test, data are presented as normalized mean±SEM plus the distribution. Cumulative distribution is analyzed by Kolmogorov-Smirnov test). ",
    "ncbi_link": "TSG6: 84397"
  },
  {
    "caption": "B) Blocking β1 integrins activity by using the specific anti-β1 Integrin monoclonal antibody prevents the PTX3-induced postsynaptic AMPARs recruitment (Ctr=1.000±0.074, PTX3=1.504±0.098, αCD29+PTX3=0.766±0.097, αCD29=0.810±0.108. Number of fields examined: 37, 33, 23, 24 respectively; one way ANOVA analysis of variance, p<0.0001 followed by post hoc Tukey test; 3 independent experiments, data are presented as normalized mean values±SEM)",
    "ncbi_link": "β1 Integrin: 24511
β1 integrins: 24511"
  },
  {
    "caption": "C) Representative images of 14DIV WT and PTX3 KO neurons stained for surface AMPARs (GluA, green), Bassoon (blue) and tubulin (red). Arrowheads point to postsynaptic GluA clusters. Scale bar: 5µm. D) Quantification of the surface synaptic AMPARs normalized to the total number of Bsn shows a reduction in PTX3 KO cultures with respect to WT (WT=1±0.065, KO=0.771±0.0.92; number of fields examined: 36 and 42 respectively; Mann-Whitney test; number of animals 5 WT and 6 PTX3 KO, data are presented as normalized mean values±SEM)",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "E) Examples of mEPSCs recorded in the indicated experimental conditions. F) Quantitation of mEPSC inter-event interval showing a rescue of mEPSC frequency in PTX3 KO cultures treated with the N-terminal fragment of PTX3 (WT=1158±34.67; WT+N-term=979.1±28.27; PTX3 KO=1263±38.99; PTX3 KO+Nterm=1008±30.14. Number of neurons: WT, Ctr=25, WT+N-term= 29; PTX3 KO, Ctr= 24; PTX3 KO+N-term=22; 3 independent experiments. Kruskall-Wallis test, p<0.0001 followed by Dunn"s test as indicated in figure, data are presented as mean±SEM). G) Quantitation of mEPSC amplitude showing a rescue in PTX3 KO cultures treated with the N-terminal fragment of PTX3 (pA, WT=20.85±0.249 WT+N-term=22.37±0.234; PTX3 KO=20.31±0.264; PTX3 KO+Nterm=23.8±0.316. Number of neurons: WT, Ctr=25, WT+N-term= 29; PTX3 KO, Ctr= 24; PTX3 KO+N-term=22; 3 independent experiments. Kruskall-Wallis test, p<0.0001 followed by Dunn"s test as indicated in figure, data are presented as",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "H) Representative images of 14DIV PTX3 KO neurons (Ctr, +N terminal PTX3, +C terminal PTX3) stained for surface AMPARs (GluA, green), Bassoon (blue) and tubulin (red). Arrowheads point to postsynaptic GluA clusters. Scale bar: 5µm. I) Quantification of the surface synaptic AMPARs normalized to the total number of Bsn shows an increase in PTX3 KO treated with N terminal fragment of PTX3 but not with the C terminal fragment (PTX3 KO=1.000±0.042, PTX3 KO+C-term=1.103±0.070, PTX3 KO+N-term=1.428±0.061. Number of fields examined: 63, 38, 57 respectively; Kruskall-Wallis test, p<0.0001 followed by Dunn\"s test; 3 independent experiments, data are presented as normalized mean values",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "J-L (J) Examples of mEPSCs recordings in WT and PTX3 KO (littermates) hippocampal slices at P8-9 showing that frequency (K) and amplitude (L) are significantly decreased in KO neurons with respect to WT (Hz: WT=1.54±0.136; PTX3 KO=0.912±0.083; Mann Whitney test. pA: WT=16.57±1.334; PTX3 KO=12.55±1.037; unpaired t-test. Data are presented as a distribution plus mean±SEM. WT: 18 cells, 4 mice; PTX3 KO: 20 cells, 5 mice)",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "N) Examples of mEPSCs recordings of P30 WT and PTX3 KO hippocampal slices. O) Quantification of mEPSC frequency showing reduced frequency in PTX3 KO mice with respect to WT (Hz: WT=2.27±0.115; PTX3 KO=1.74±0.136. WT: 10 cells, 4 mice; PTX3 KO: 11 cells, 5 mice. Unpaired t-test p=0.008. Data are presented as a distribution plus mean±SEM). P, Q (P) No difference in the average amplitude is evident (pA: WT=11.95±0.589; PTX3 KO=10.69±0.438; unpaired t-test p=0.099. Data are presented as a distribution plus mean±SEM. WT: 10 cells, 4 mice; PTX3 KO: 11 cells, 5 mice); however the cumulative probability plot of amplitudes (Q) for mEPSCs in WT and PTX3 KO shows that there is a significant shift in the distribution by the Kolmogorov-Smirnov test (p <0.0001, D=0.112). ",
    "ncbi_link": "PTX3: 689388"
  },
  {
    "caption": "Cell viability analysis using CellTiter-Glo of BN175 CRISPR/Cas9 Ripk1 and Casp-8 knockouts (KO) cells treated with the indicated agents for 18 and 48 hrs (n = 3 biological replicates). Cell viability values are displayed as a percentage of the relative untreated control. SM represents SM-164. Error bars represent SD and a one-way Anova was performed to compare the mean value of each treatment to the treated BN175 CRISPR/Cas9 control (Ctrl), **** P ≤ 0.0001.",
    "ncbi_link": "Casp-8: 64044
Ripk1: 306886"
  },
  {
    "caption": "Cell death analysis by Celigo of PI-positive HT1080 cells treated with the indicated agents for 72 hrs following siCTRL, siRIPK1 or siCASP-8 knockdown for 48 hrs (n = 3 biological replicates). DMSO (Unt), TNF (10 ng/ml) and SM (100 ng/ml). SM represents SM-164. Error bars represent SD and a one-way Anova was performed, **** P ≤ 0.0001.",
    "ncbi_link": "CASP-8: 841
RIPK1: 8737"
  },
  {
    "caption": "Cell viability analysis using CellTiter-Glo of A375 cells treated with the indicated drugs for 24 hrs following siCTRL, siRIPK1 or siCASP-8 knockdown for 48hrs (n = 3 biological replicates). Cell viability values are displayed as a percentage of the relative untreated control. DMSO (Unt), TNF (10 ng/ml) and SM (100 ng/ml). SM represents SM-164. Error bars represent SD and a one-way Anova was performed to compare the mean value of each treatment to the treated A375 siCTRL, **** P ≤ 0.0001.",
    "ncbi_link": "CASP-8: 841
RIPK1: 8737"
  },
  {
    "caption": "Cell viability analysis using CellTiter-Glo of BN175 CRISPR/Cas9 Ripk1 and Casp-8 KO cells treated with the indicated agents for 24 hrs (n = 3 biological replicates). Cell viability values are displayed as a percentage of the relative untreated control. DMSO (Unt), SM (100 ng/ml) and Riboxxol (1 µg/ml). SM represents SM-164. Error bars represent SD and a one-way Anova was performed to compare the mean value of each treatment to the treated BN175 CRISPR/Cas9 control (Ctrl), **** P ≤ 0.0001.",
    "ncbi_link": "Casp-8: 64044
Ripk1: 306886"
  },
  {
    "caption": "A Representative auditory brainstem response (ABR) waveforms evoked by 16 kHz tone-bursts in p53wt mice treated with saline (black plot) or CDDP (green plot), and p53-/- mice treated with saline (light blue plot) or CDDP (dark blue plot) for 5 days.B ABR thresholds recorded in p53wt mice before (gray plot) and after 5 days of saline (black plot) or CDDP treatments (green plot), and ABR thresholds recorded in p53-/- mice before (light gray plot), and after 5 days of saline (light blue plot) or CDDP treatment (dark blue plot).C Mean ABR threshold from 4 kHz to 32 kHz derived from B. Data are expressed as mean ± SEM (saline treated-group: n=7, CDDP treated-group: n=12). One-way ANOVA test followed by post hoc Tukey's test (**P ≤ 0.008, p53wt+CDDP, d5 vs. p53wt, before or p53wt+CDDP, d5 vs. p53-/- + CDDP, d5).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "D Representative scanning electron microscopy micrographs showing the basal regions of cochleae from CDDP-treated p53wt and p53-/- mice after 5 days. Scale bar=15µm.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "E Cytocochleograms representing the percentage of surviving hair cells in four cochlear regions located at 1.1, 2.6, 3.5 or 4.1 mm from the cochlear apex provided from saline-treated p53wt mice (black bars), CDDP-treated p53wt mice (green bars) or p53-/- mice (blue bars), after 5 days (n=5 per group). Data are expressed as mean ± SEM. Kruskal-Wallis test followed by post hoc Dunn's test (**P ≤ 0.008, p53wt+CDDP, d5 vs. p53wt+saline, d5 or p53wt+CDDP, d5 vs. p53-/- + CDDP, d5).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "F ABR thresholds from p53wt mice recorded prior to (gray plot) or after 5 days systemic treatment with: DMSO (yellow plot), CDDP+DMSO (green plot), CDDP+PFT-α (pink plot).G Mean ABR threshold from 4 kHz to 32 kHz derived from F. Data are expressed as mean ± SEM (DMSO treated-group: n=7; CDDP+DMSO treated-group: n=12; CDDP+ PFT-α-treated group: n=12). One-way ANOVA test followed by post hoc Tukey's test (***P ≤ 0.0005, CDDP+DMSO, d5 vs. before or CDDP+DMSO, d5 vs. CDDP+PFT-α, d5).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "H Cytocochleograms representing the percentage of surviving hair cells in four cochlear regions located at 1.1, 2.6, 3.5 or 4.1 mm from the cochlear apical end taken from p53wt mice treated with: DMSO (yellow bars), CDDP+DMSO (green bars), CDDP+PFT-α (pink bars), after 5 days (n=5 per group). Data are expressed as mean ± SEM. Kruskal-Wallis test followed by post hoc Dunn's test (**P ≤ 0.008, CDDP+DMSO, d5 vs. DMSO, d5 or CDDP+DMSO, d5 vs. CDDP+PFT-α, d5).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "I ABR thresholds from p53wt mice recorded prior to (gray plot and black plot for left and right ear, respectively) or after 5 days of systemic treatment with CDDP plus intratympanic injection of DMSO into the left ear (green plot), and of PFT-α into the right ear (pink plot).J Mean ABR threshold from 4 kHz to 32 kHz derived from I. Data are expressed as mean ± SEM (n=14). One-way ANOVA test followed by post hoc Tukey's test (***P = 0.0003 , CDDP+left ear, DMSOvs. before, left ear or CDDP + left ear, DMSOvs. CDDP + right ear, PFT-α.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "A ABR thresholds recorded prior to (gray plot) or at day 28 in HBCx-90 (TP53 wt) bearing-mice received systemic treatment with: DMSO (black plot), PFT-α (yellow plot), CDDP (green plot), CDDP+PFT-α (pink plot).B Mean ABR threshold from 4 kHz to 32 kHz derived from A. Data are expressed as mean ± SEM (before: n=20; DMSO: n=5; PFT-α: n=5; CDDP: n=5; CDDP+PFT-α: n=5). One-way ANOVA test followed by post hoc Tukey's test (***P = 0.0002, CDDP vs. before; CDDP vs. CDDP+PFT-α.E ABR thresholds recorded prior to (gray plot) or at day 35 in HBCx-14 (TP53 mutant) bearing-mice received systemic treatment with: DMSO (black plot), PFT-α (yellow plot), CDDP (green plot), CDDP+PFT-α (pink plot).F Mean ABR threshold from 4 kHz to 32 kHz derived from E. Data are expressed as mean ± SEM (before: n=30; DMSO: n=5; PFT-α: n=5; CDDP: n=10; CDDP+PFT-α: n=10). One-way ANOVA test followed by post hoc Tukey's test (***P = 0.0003, CDDPvs. before or CDDPvs. CDDP+PFT-α.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "A Representative confocal images of microvessels in transversal tumor sections from HBCx-14 (TP53mutant) tumors treated with either DMSO, CDDP or a combination of CDDP and PFT-α. The sections were immunolabeled for CD31 (red) and viewed with a 20x objective. The basal-like breast cancer cells were immunolabeled in green with an antibody against cytokeratin 5 and 8. Upper right panel is a 2D projection from the white boxed area in upper left panel. The red area corresponds to CD31 labeled endothelial area and the white area represents the lumen area. The white line shows the vessel perimeter. Scale bars: left panel=50 µm, right panels=35 µm. The tumor samples were collected at day 21.B Histograms representing the percentage of vascular area calculated using 2D reconstruction image analysis and the formula: vessel/vascular area = area of CD31-positive objects + lumen area per field area × 100 %. The both HBCx-14 (TP53mutant) and HBCx-90 (TP53wt) tumors from the different treated groups were collected at day 21 (n=4 sections/tumor and 3-4 tumors/group). Data are expressed as mean ± SEM. Kruskal-Wallis test followed by post hoc Dunn's test (***P ≤0.0004, CDDPvs. DMSO or CDDPvs. CDDP+PFT-α).",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "C Representative confocal images of cleaved caspase 3 positive cells (red) in the transversal tumor sections and viewed with a 20x objective. The stromal compartments were immunolabeled in green with an antibody against vimentin. HBCx-14 (TP53mutant) tumors from the different treated groups were collected at day 18. Scale bar=50 µm. c-cas-3: cleaved caspase 3.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "D Representative western blot analysis using antibodies against β-actin, p53 and p21 in tumor extracts from HBCx-14 (TP53mutant) and HBCx-90 (TP53 wt) tumors treated with either DMSO or CDDP and collected at day 18. Note the higher CDDP-induced increase of p53 and p21 expression in TP53wt HBCx-90tumors.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "E, F Representative western blot analysis using antibodies against β-actin, p-Chk1, Beclin 1, LC3-I/II and Rab7 in tumor extracts from HBCx-14 (TP53mutant) and HBCx-90 (TP53 wt) tumors treated with either DMSO, PFT-α, CDDP or a combination of CDDP and PFT-α. The tumor samples were collected at day 18.G, H, I Histograms representing the levels of Beclin 1, LC3-II and Rab7 in HBCx-14 and HBCx-90tumors treated with the different regimens (n=3-4 tumors per group, all experiments were performed in triplicate). Actin served as a loading control. Data are expressed as mean ± SEM. One-way ANOVA test followed by post hoc Tukey's test (G: *P = 0.03, **P =0.006 , ***P ≤ 0.0004 ; H: *P =0.02, ***P = 0.0005 ; I: *P =0.03, ***P ≤ 0.0006 , CDDPvs. DMSO or CDDPvs. CDDP+PFT-α).",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "(A) HT29 cells were infected with Shigella WT, S325, or ospD deletion mutants, and incubated for 8 h. Aliquots of cellular supernatants were subjected to cytotoxicity assays. *P<0.05 (one-way ANOVA).",
    "ncbi_link": "ospD: 13917051"
  },
  {
    "caption": "(B) HT29 cells were infected with Shigella WT or ∆ospD3 and incubated for 8 h. Infected cells were fixed and subjected to TUNEL and PI staining. Percentages of positive cells (TUNEL, green; PI, red) are shown in graph at right. The nuclei were stained with DAPI (blue). Scale bar: 100 μm. n.s., not significant; *P<0.05 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "(C) HT29 cells were infected with Shigella WT, S325, or ∆ospD3 and incubated for 8 h. Infected cells were subjected to Giemsa staining. Arrows indicate cells in which the cytoplasm disappeared. Scale bar: 20 μm.",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "(A) HT29 cells were infected with Shigella WT, S325, or ospD deletion mutants, and incubated for 8 h. Cell lysates were subjected to immunoblotting.",
    "ncbi_link": "ospD: 13917051"
  },
  {
    "caption": "(D HT29 cells treated with the indicated siRNAs were infected with Shigella WT or ∆ospD3. Cell lysates and aliquots of cellular supernatants were subjected to immunoblotting (top) and cytotoxicity assays (bottom), respectively. The knockdown efficiency of the indicated siRNAs was assessed by immunoblotting (inset). n.s., not significant; *P<0.05 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "E) HT29 cells treated with the indicated siRNAs were infected with Shigella WT or ∆ospD3. Cell lysates and aliquots of cellular supernatants were subjected to immunoblotting (top) and cytotoxicity assays (bottom), respectively. The knockdown efficiency of the indicated siRNAs was assessed by immunoblotting (inset). n.s., not significant; *P<0.05 (unpaired two-tailed Student's t-test).",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "(B) 293T cells were transfected with Myc-tagged ospD expression plasmids. After 24 h, cells were harvested and subjected to immunoblotting. Arrows indicate cleaved RIPK1.",
    "ncbi_link": "Myc: 
ospD: 13917051"
  },
  {
    "caption": "D) 293T cells were transfected with a series of plasmids expressing ospD3 point mutants. After 24 h, cells were harvested and subjected to immunoblotting. Arrows indicate cleaved RIPK1.",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "(E HT29 cells were infected with Shigella WT, S325, ∆ospD3, ∆ospD3/D3 (∆ospD3 complemented with wild-type ospD3), or ∆ospD3/D3CS (∆ospD3 complemented with a protease activity-deficient mutant, in which the cysteine residue at position 64 was replaced by serine) strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to immunoblotting",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "F) HT29 cells were infected with Shigella WT, S325, ∆ospD3, ∆ospD3/D3 (∆ospD3 complemented with wild-type ospD3), or ∆ospD3/D3CS (∆ospD3 complemented with a protease activity-deficient mutant, in which the cysteine residue at position 64 was replaced by serine) strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to cytotoxicity assays",
    "ncbi_link": "ospD3: 13917149"
  },
  {
    "caption": "(D) HT29 cells were infected with Shigella WT or ∆ospC1 mutant and incubated for 8 h. Infected cells were then fixed and stained with cleaved caspase-8 (green), rhodamine-phalloidin (red), and DAPI (blue). Percentages of positive cells are shown in the graph at right (*P<0.05; unpaired two-tailed Student's t-test). Scale bar: 100 μm.",
    "ncbi_link": "ospC1: 13917148"
  },
  {
    "caption": "(F) HT29 cells were infected with Shigella WT, S325, or ∆ospC1 strains, and incubated for up to 8 h. After incubation for the indicated times, cells were subjected to real-time Annexin V apoptosis assay. Annexin V binding is reported as relative light units (RLU) in infected samples minus the value in uninfected samples. *P<0.05 (one-way ANOVA).",
    "ncbi_link": "ospC1: 13917148"
  },
  {
    "caption": "(A HT29 cells were infected with Shigella WT, ∆ospC1, ∆ospD3, ∆ospC1∆ospD3, or ∆ospC1∆ospD3/ospC1 (∆ospC1∆ospD3 complemented with ospC1) strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to immunoblotting",
    "ncbi_link": "ospC1: 13917148
ospD3: 13917149"
  },
  {
    "caption": "B) HT29 cells were infected with Shigella WT, ∆ospC1, ∆ospD3, ∆ospC1∆ospD3, or ∆ospC1∆ospD3/ospC1 (∆ospC1∆ospD3 complemented with ospC1) strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to cytotoxicity assay",
    "ncbi_link": "ospC1: 13917148
ospD3: 13917149"
  },
  {
    "caption": "(C) HT29 cells were infected with Shigella WT, ∆ospD3, or ∆ospC1. Cell lysates obtained at the indicated time points were subjected to immunoblotting.",
    "ncbi_link": "ospC1: 13917148
ospD3: 13917149"
  },
  {
    "caption": "(D HT29 cells treated with DMSO or caspase-8 inhibitor were infected with Shigella WT, ∆ospC1, ∆ospD3, or ∆ospC1∆ospD3 strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to immunoblotting",
    "ncbi_link": "ospC1: 13917148
ospD3: 13917149"
  },
  {
    "caption": "E) HT29 cells treated with DMSO or caspase-8 inhibitor were infected with Shigella WT, ∆ospC1, ∆ospD3, or ∆ospC1∆ospD3 strains and incubated for 8 h. Cell lysates and aliquots of cellular supernatants were subjected to cytotoxicity assay",
    "ncbi_link": "ospC1: 13917148
ospD3: 13917149"
  },
  {
    "caption": "(F) HT29 cells treated with the control or caspase-8 siRNAs were infected with the indicated Shigella strains and incubated for 8 h. Cell lysates were subjected to immunoblotting. The knockdown efficiency of the indicated siRNAs was assessed by immunoblotting.",
    "ncbi_link": "caspase-8: 841"
  },
  {
    "caption": "scRNA-Seq of the expression of the entire glycolytic pathway or of glucose phosphate isomerase only (GPI) in primary CD4+ T-cells infected in vitro (D,E) or CD4+ T-cells of PLWH (F). In panels (D, E), cells were infected with VSVG-HIV-1-GFP and sorted for viral expression as detailed in (Golumbeanu et al, 2018). Following latency establishment, cells were left untreated or HIV-1 expression was reactivated through suberoyl anilide hydroxamic acid (SAHA) or α-CD3-CD28 engagement. Clusters 1 and 2 were identified by principal component analysis as described in (Golumbeanu et al, 2018). In panel (F), CD4+ T-cells were isolated from total blood of PLWH under ART as described in (Cohn et al, 2018). Viral expression was reactivated by treatment with phytohemagglutinin (PHA) and cells were sorted using antibodies against Env and Gag. Sorted cells were then subjected to scRNA-Seq analysis. The expression level of the HUMAN-GLYCOLYSIS pathway in (D) was calculated as the average expression of genes comprising the gene list; expression levels in cluster 1 and 2 were compared using Wilcoxon rank sum test. For panels (E, F), significance of GPI differential expression level between clusters (E) or between control and Env+ Gag+ conditions (F) was assessed by the Wilcoxon rank sum test encoded in FindMarkers Seurat R function. ** p< 0.01, *** p< 0.001; *** p< 0.0001. For panels (D,E) n = 1 donor, 43 cells (untreated), 90 cells (SAHA ), 91 cells (TCR), for panel (F) n = 3 donors, 109 cells (control) and 85 cells (Gag+ Env+).",
    "ncbi_link": "GFP: 
glucose phosphate isomerase: 2821
GPI: 2821
TCR: 6955///6957"
  },
  {
    "caption": "Relative expression of HIV-1 gag in cells infected with Tat-deficient HIV-1pNL4-3 as compared to cells infected with wild type HIV-1 pNL4-3.",
    "ncbi_link": "gag: 155030
Tat: 155871"
  },
  {
    "caption": "relative expression of the limiting rate enzyme of the pentose phosphate pathway, i.e. G6PD (B) in HIV-1 infected as compared to mock infected cells.",
    "ncbi_link": "G6PD: 2539"
  },
  {
    "caption": "relative expression of genes regulating the thioredoxin and glutathione antioxidant pathways, i.e. TrxR1 (C) and GCLC (D), in HIV-1 infected as compared to mock infected cells.",
    "ncbi_link": "GCLC: 2729
TrxR1: 7296"
  },
  {
    "caption": "Reactivation from HIV-1 latency (A) and relative cell viability (B) in primary Th17 cells following 24 h treatment with the Trx inhibitor auranofin (AF; 500 nM), the GSH inhibitor buthionine sulfoximine (BSO; 250 μM), or a combination of the two. GFP-HIV-1 expression was determined by FACS. Data are expressed as mean ± SD of three replicates and were analyzed by One-Way ANOVA followed by Tukey's post-test (A) or Two-Way ANOVA followed by Sidak´s post-test (B). Solid lines represent the means.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B.  Survival frequencies observed after DSB  induction at TEL6R in WT, dnl4Δ, sir4Δ cells, expressing or not high levels of Sir3p  (oeSir3 and WT respectively). Error bars indicate survival  standard error (SEM) of at least three independent experiments. C. Survival frequencies observed after   DSB  induction at LYS2  in the indicated strains. Error bars indicate survival standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "dnl4: 854166
LYS2: 852412
Sir3: 851163
sir4: 851813"
  },
  {
    "caption": "F. Representative images of  Mre11-YFP foci in response to an I-SceI-induced DSB  at LYS2 in WT cells, expressing or not high levels of Sir3p (oeSir3 and WT respectively). Scale bars are 2 μm. G. Quantification of cells with   DSB  induced  Mre11-YFP foci after   DSB induction at LYS2 I-SceI cleavage site in WT, sae2Δ and Sir3 overexpressing (oeSir3) strains. Error bars indicate  survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "LYS2: 852412
sae2: 852700
I-SceI: 854590
Sir3: 851163"
  },
  {
    "caption": "H. Survival  frequencies after DSB  induction at LYS2 locus, in strains where  SIR3 is expressed from its native, pADH1 or pGPD promoters respectively and in which SAE2 is expressed or not from a high copy number 2µ plasmid. Fold increase in  Sir3 protein by pAHD1 or pGPD is indicated. Error bars indicate survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "ADH1: 854068
AHD1: 854068
LYS2: 852412
SAE2: 852700
SIR3: 851163
Sir3: 851163
GPD: 853106"
  },
  {
    "caption": "A. Representative images of  Sir3-mCherry and Sae2-GFP signal in WT and SIR3 overexpressing cells. Scale bars are 2 μm.",
    "ncbi_link": "SIR3: 851163"
  },
  {
    "caption": "B.   Sir3-binding at TEL6R in untagged, WT, sir3Δ cells or in cells overexpressing Sir3 (oeSir3). Binding is probed by  ChIP-qPCR 0.2 (red arrows) and 1kb (blue arrows) from  telomeres and at the OGG1  control locus using antibodies against Sae2-GFP. The mean of three independent biological replicates is shown and error bars correspond to the variation between replicates (SEM).",
    "ncbi_link": "OGG1: 854942
sir3: 851163
Sir3: 851163"
  },
  {
    "caption": "C. Co-immunoprecipitation between  Sir3 and Sae2-GFP from cells overexpressing  Sir3, analysed by Western blot with anti-GFP and anti-Sir3 antibodies. D. Co-immunoprecipitation between Sir3  and Sae2-GFP from WT cells using antibodies against Sae2-GFP, analysed by Western blot.",
    "ncbi_link": "Sir3: 851163"
  },
  {
    "caption": "D.  Yeast two-hybrid interaction  analysis  between Sae2C and Sir3SaID domains in WT or sir4Δ cells. Growth on -His + 3AT  and blue coloration on X-gal indicate an  interaction.",
    "ncbi_link": "sir4: 851813"
  },
  {
    "caption": "B. Representative images of two hybrid assays in the yKD1991 strain testing the interaction of the WT or the mutant SIR3SaID fragment isolated from the screen with SAE2C or SIR4C. C. Representative images of two hybrid assays  testing the interaction of the WT or the mutant SIR3SaIDT557I fragment with SAE2C or SIR4C.",
    "ncbi_link": "SIR3: 851163"
  },
  {
    "caption": "A. Survival frequencies after    DSB induction at  LYS2 locus in WT or sae2Δ strains where the Sir3SaID or Sir3SaIDT557I domains are overexpressed from a GPD promoter at the SIR3 locus. Error bars indicate  survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "LYS2: 852412
sae2: 852700
Sir3: 851163
SIR3: 851163
GPD: 853106"
  },
  {
    "caption": "B. Representative images of Sae2-GFP  in WT cells and in cells overexpressing either full-length  Sir3 or the sir3SaID domain. Scale bars are 2 μm.",
    "ncbi_link": "Sir3: 851163
sir3: 851163"
  },
  {
    "caption": "G. Co-immunoprecipitation between Sae2-GFP and  Sir3 from untagged, Sae2-GFP WT cells, and Sae2-GFP cells overexpressing WT Sir3  (oeSir3, WT), Sae2-GFP sir3Δ or Sae2-GFP overexpressing the  sir3-T557I mutant (oeSir3, T557I) using antibodies against  Sae2-GFP, analysed by Western blot with anti-GFP and anti-Sir3 antibodies.",
    "ncbi_link": "GFP: 
Sae2: 852700
Sir3: 851163
sir3: 851163"
  },
  {
    "caption": "A. Survival  frequencies after  DSB induction at LYS2 locus in the indicated strains. Error bars indicate survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "LYS2: 852412"
  },
  {
    "caption": "C.  Survival frequencies after  DSB induction at LYS2 locus in the indicated strains. Insertion of the strong TEF1p promoter upstream of the SIR4 ORF leads to  Sir4 overexpression. Insertion of the ADH1p promoter upstream of SIR3  leads to mild Sir3 overexpression. Error bars indicate survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "ADH1: 854068
LYS2: 852412
SIR3: 851163
Sir3: 851163
SIR4: 851813
Sir4: 851813
TEF1: 856195"
  },
  {
    "caption": "E. Representative images of two hybrid assays testing the interaction  between the full-length Sir3 and full-length Sae2 proteins in WT cells expressing or not high levels of Sir4  (oeSir4 and WT respectively).",
    "ncbi_link": "Sir4: 851813"
  },
  {
    "caption": "A. Relative fold enrichment of Sae2 at 0.2 kb from I-SceI site was evaluated by qPCR after ChIP with anti-GFP antibodies. The error bars indicate the variation between at least three biological replicas (SEM). B. Relative fold enrichment of  Sae2 at 0.2 kb from TEL6R after  DSB  induction at the LYS2 I-SceI site was evaluated by qPCR after ChIP with anti-GFP  antibodies. The error bars indicate the variation between at least three biological replicas (SEM). Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "LYS2: 852412
I-SceI: 854590"
  },
  {
    "caption": "D. Survival frequencies after  DSB induction at LYS2  locus in  sae2-E267E mutant cells overexpressing or not full-length Sir3  (oeSir3). Error bars indicate survival  standard error (SEM) of at least three independent experiments. Data information: Significance was determined using 2-tailed, unpaired Student's t test. *P-value 0.01 to 0.05, significant; **P-value 0.001 to 0.01, very significant; ***P-value 0.0001 to 0.001, extremely significant; ****P < 0.0001, extremely significant; P ≥ 0.05, not significant (ns).",
    "ncbi_link": "LYS2: 852412
sae2: 852700
Sir3: 851163"
  },
  {
    "caption": "A TRAF6 expression in differentiating CD4+ T cells. Naïve CD4+ T cells were obtained from wild type C57BL/6 mice by FACS and activated with anti-CD3/CD28 (1µg, and 2µg/ml) for the indicated times in the presence of distinct Thelper lineage-directing cytokines or under neutral activation conditions (Th0). After total RNA extraction and cDNA conversion, RT-PCR determined of Traf6 mRNA in differentiating Th0, Th1, Th17 and iTregs was determined.",
    "ncbi_link": "Traf6: 22034
TRAF6: 22034"
  },
  {
    "caption": "B TRAF6 mRNA expression by human Tregs and non-Treg CD4+ T cell. Human Tregs (CD3+/CD4+/CD8-/CD25HIGH/CD127low/CD39+) and non-Treg CD4+ T cells (CD3+/CD4+/CD8-/CD25-) were obtained from the peripheral blood of healthy donors by FACS after Ficoll-Paque PLUS gradient centrifugation and magnetic bead enrichment of CD4+ T cells. TRAF6 mRNA was measured by qRT-PCR.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "C, D Evidence of lymphoproliferative disease in Traf6fl/flFoxp3Cre+ mice. (C) Spleens and lymph nodes were recovered from Traf6fl/flFoxp3Cre+ mice and Traf6fl/fl littermates at 8 weeks of age (Scale bars: 5 mm). (D) The cellularity of the lymphoid tissues of Traf6fl/flFoxp3Cre+ mice and their Traf6fl/fl Foxp3Cre- littermates was determined (8 mice/group).",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Traf6: 22034"
  },
  {
    "caption": "E, H Effect of Treg-specific TRAF6-deficiency on baseline T cell activation. The frequencies of effector cells (CD44high/CD62Llow), memory cells (CD44high/CD62Lhigh) and naïve cells (CD44low/CD62Lhigh) in the CD4+ T cell compartments of Traf6fl/fl and Traf6fl/flFoxp3Cre+ mice were determined by flow cytometry (5 mice/group).",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
TRAF6: 22034
Traf6: 22034"
  },
  {
    "caption": "F, I Effect of Treg-specific TRAF6-deficiency on baseline T cell activation. The frequencies of effector cells (CD44high/CD62Llow), memory cells (CD44high/CD62Lhigh) and naïve cells (CD44low/CD62Lhigh) in the CD8+ T cell compartments of Traf6fl/fl Foxp3Cre- (wild type) and Traf6fl/flFoxp3Cre+ mice were determined by flow cytometry (5 mice/group).",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
TRAF6: 22034
Traf6: 22034"
  },
  {
    "caption": "G, J Impact of TRAF6-expression on in vitro Treg differentiation. naïve CD4+ T cells were isolated from Traf6fl/flFoxp3Cre+ and Traf6fl/fl mice and differentiated into iTregs. Conditions of sub-optimal TGFβ concentrations (0.5ng/ml, 0.05ng/ml) were tested as well and intracellular FOXP3 was measured after 4 days.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
TRAF6: 22034
Traf6: 22034"
  },
  {
    "caption": "A In vivo suppressive function of WT and Traf6fl/flFoxp3Cre+ Tregs. Tregs from the indicated mice (CD45.2+) were isolated by FACS, as were naïve (CD62Lhigh/CD25-) CD4+ responder T cells from congenically distinct (CD45.1+) donor mice. Tregs and Tresponders were mixed at a 1:5 (2x105:10x105) ratio before injection into Rag2-/- mice. 7 days later, spleens were harvested, and the relative frequencies and absolute numbers of each transferred cell populations were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Rag2: 19374
Traf6: 22034"
  },
  {
    "caption": "B Implanted B16 melanoma growth in Traf6fl/flFoxp3Cre+ and wild type (Traf6fl/flFoxp3Cre-) mice. 1x105 B16F10 cells were injected subcutaneously (s.c.) into the shaved flanks of the indicated mice (n= 5/group). Tumor volumes were monitored every 3 days.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Traf6: 22034"
  },
  {
    "caption": "C, D Proinflammatory cytokine production in tumor-bearing mice with and without Treg-specific TRAF6 expression. Cell suspensions of the tumor-draining lymph node and tumor-infiltrating leukocytes (TILs) were recovered after 21 days of tumor growth. Ex vivo stimulation with PMA and ionomycin in the presence of Golgistop for 5 hour preceded intracellular staining for IFNγ and IL-17 and flow cytometry analysis.",
    "ncbi_link": "TRAF6: 22034"
  },
  {
    "caption": "E, F FOXP3 expression by CD4+ T cells in tumor bearing Traf6fl/flFoxp3Cre+ and wild type (Traf6fl/flFoxp3Cre-) mice. The frequency of FOXP3+ cells in the CD4+ cells of tumor-draining lymph nodes (dLN), peripheral, non-tumor draining lymph nodes (pLN), spleens, and TILs were determined by flow cytometry.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Traf6: 22034"
  },
  {
    "caption": "A Assessment of K63-type ubiquitination of FOXP3 upon expression of wild type and catalytically deficient TRAF6 mutants. 293T cells were transfected with the given combinations of vectors encoding wild type TRAF6, the enzymatically deficient L74H or C70A TRAF6 mutants, HA-FOXP3, and FLAG-labeled ubiquitin molecules possessing a single lysine residue (K63) that restrain the possible ubiquitin monomer linkages on polyubiquitinated proteins to the K63-type only. Cells were lysed and proteins modified by K63-ubiquitin chains were recovered from lysates by pulling down using a bead-immobilized K63-specific TUBE reagent. The presence of FOXP3 among these modified proteins was determined by immunoblotting as were levels of FOXP3 and TRAF6 in the pre-IP whole cell lysate (WCL).",
    "ncbi_link": "FLAG: 
HA: 
ubiquitin: 
FOXP3: 20371
TRAF6: 22034"
  },
  {
    "caption": "B Co-immunoprecipitation (co-IP) of FOXP3 with TRAF6 and its facilitation of K63-linked ubiquitination. 293T cells expressing the indicated constructs encoding HA-FOXP3 and FLAG-TRAF6 were lysed and incubated with bead immobilized anti-FLAG antibodies. FOXP3 molecules co-IPed in this manner were resolved by SDS PAGE and detected by immunoblotting with anti-HA antibodies.",
    "ncbi_link": "FLAG: 
HA: 
FOXP3: 20371
TRAF6: 22034"
  },
  {
    "caption": "C　293T cells were transfected with the indicated combinations of expression constructs encoding HA-FOXP3, Myc-TRAF6, and FLAG-tagged ubiquitin molecules - either wild type (FLAG-Ub), or a variant with a K-to-R mutation at either lysine residue 48 (K48R) or 63 (K63R) responsible for preventing K48- and K63-type polyubiquitination, respectively. .",
    "ncbi_link": "FLAG: 
HA: 
Myc: 
ubiquitin: 
FOXP3: 20371
TRAF6: 22034"
  },
  {
    "caption": "E Degree of K63 ubiquitination in the cellular FOXP3 pools of Traf6fl/flFoxp3Cre+ and Traf6wt/wtFoxp3Cre+mice. CD4+/YFP+ cells from Traf6fl/flFoxp3Cre+ ("Traf6-/-") or wild type Traf6wt/wtFoxp3Cre+mice ("Traf6+/+") were isolated by FACS, lysed and either total FOXP3 (right) or K63-ubiquitin-modified proteins (left) were immunoprecipitated. Levels of polyubiquitinated FOXP3 were observed in each by probing with antibodies specific for anti-K63-ubiquitin and FOXP3, respectively, and levels of total FOXP3 and actin were also measured by immunoblot analysis of whole cell lysate.",
    "ncbi_link": "Cre: 2777477
FOXP3: 20371
Foxp3: 20371
Traf6: 22034"
  },
  {
    "caption": "A Immunoblot analysis of TRAF6-mediated ubiquitination of wild type, and mutant FOXP3 molecules. 293T cell lines were transfected with a normal HA-tagged Foxp3 construct, another encoding a ubiquitination resistant mutant in which all lysine residues were replaced by arginines (20R), or one of 20 single lysine-containing constructs with only the indicated lysine residue available for modification. These cell lines also received expression vectors encoding TRAF6 and ubiquitin molecules labeled with Myc and FLAG tags, respectively. Negative controls did not receive TRAF6 or expressed FOXP3 alone. Labeled FOXP3 proteins were pulled down from cell lysates (anti-HA) and ubiquitinated species were visualized by immunoblotting for FLAG.",
    "ncbi_link": "FLAG: 
HA: 
Myc: 
ubiquitin: 
Foxp3: 20371
TRAF6: 22034"
  },
  {
    "caption": "B Assessing the impact of K262 mutation on FOXP3 ubiquitination by TRAF6. 293T cells were transfected with combinations of expression constructs encoding Myc-TRAF6, FLAG-ubiquitin, and an HA-tagged FOXP3 molecule that was either normal (HA-FOXP3) or possessed a K-to-R mutation at residue 262 (K262R). FOXP3 proteins were pulled down with anti-HA beads and either ubiquitinated proteins or total FOXP3 proteins were detected by probing for FLAG and HA, respectively.",
    "ncbi_link": "FLAG: 
HA: 
Myc: 
ubiquitin: 
FOXP3: 20371
TRAF6: 22034"
  },
  {
    "caption": "A Impact of K63-ubiquitination loss on FOXP3's gene silencing capacity. Jurkat T cells transfected with a wild type Foxp3 expression vector, one encoding the K262R mutant, or an empty (control) vector also received a duel luciferase reporter construct where luciferase expression was under the control of the Il2 promoter. After activation with PMA and ionomycin for 8 hours, luciferase activity was assayed.",
    "ncbi_link": "luciferase: 
Foxp3: 20371
FOXP3: 20371
Il2: 3558"
  },
  {
    "caption": "B IL-2 production in the presence of wild type and K63-ubiquitination resistant FOXP3. Naïve CD4+ T cells isolated from Traf6fl/flCD4Cre+ or WT mice were activated overnight by anti-CD3/CD28 antibodies, then transduced by retroviruses carrying normal Foxp3, the K262R mutant, or an empty vector. Ires-GFP in the retroviral vector serves as an internal control. GFP+ cells were sorted out 48 hours post-transduction. The sorted cells were cultured for one additional day. Culture supernatants were collected for measuring the levels of IL-2 by ELISA.",
    "ncbi_link": "CD4: 12504
Cre: 2777477
Foxp3: 20371
FOXP3: 20371
Traf6: 22034"
  },
  {
    "caption": "C Cellular distribution of wild type and K262R FOXP3. Hela cells were transfected with expression vectors encoding either wild type FOXP3 or the K262R mutant. The relative overlap of FOXP3 protein signal and DAPI-stained nuclei was observed by fluorescence microscopy. (blue: DAPI, green: FOXP3, Scale bars: 50 μm).",
    "ncbi_link": "FOXP3: 20371"
  },
  {
    "caption": "D Immunostaining of FOXP3 in Traf6fl/flCD4Cre+ and wild type (Traf6fl/flCD4Cre-) derived suspensions of lymph node and spleen cells. (blue: DAPI, green: FOXP3, Scale bars: 50 μm).",
    "ncbi_link": "CD4: 12504
Cre: 2777477
Traf6: 22034"
  },
  {
    "caption": "E Quantification of FOXP3 distribution in murine Tregs. The degree of FOXP3-nuclear coIocalization in CD4+/FOXP3+ cells isolated from the lymph nodes and spleens of Traf6fl/flCD4Cre+ and wild type (Traf6fl/flCD4Cre-) mice was determined by Imagestream analysis, and the frequencies of cells with either a low or high probability of nuclear FOXP3 distribution are shown (red: nuclear stain, green:FOXP3, Scale bars: 10 um).",
    "ncbi_link": "CD4: 12504
Cre: 2777477
Traf6: 22034"
  },
  {
    "caption": "The in vitro suppressive potency of wild type- and K262R Foxp3-expressing T cells. Naïve CD4+ T cells were purified from Thy1.1+ BALB/c mice and subjected to retroviral transduction to express either wild type FOXP3 or a K262R mutant resistant to ubiquitination that lysine residue 262. These engineered "Tregs" were then co-cultured with naïve responder CD4+ T cells stained with CFSE at the indicated ratios and activated with anti-CD3/CD28 antibodies. Dilution of CFSE signal by the responder populations (i.e. proliferation) was assessed by flow cytometry.",
    "ncbi_link": "Foxp3: 20371
FOXP3: 20371"
  },
  {
    "caption": "The in vitro suppressive potency of wild type- and K262R Foxp3-expressing T cells. Naïve CD4+ T cells were purified from Thy1.1+ BALB/c mice and subjected to retroviral transduction to express either wild type FOXP3 or a K262R mutant resistant to ubiquitination that lysine residue 262. These engineered \"Tregs\" were then co-cultured with naïve responder CD4+ T cells stained with CFSE at the indicated ratios and activated with anti-CD3/CD28 antibodies. Dilution of CFSE signal by the responder populations (i.e. proliferation) was assessed by flow cytometry.",
    "ncbi_link": "Foxp3: 20371
FOXP3: 20371"
  },
  {
    "caption": "C In vivo suppression of colitis by wild type- and K262R mutant-Foxp3 expressing T cells. 2x105 naïve CD4+ transductants from A were mixed with 1x106 colitogenic naïve CD4+ T cells from wild type mice and transferred i.v. into Rag2-/- mice. Rag2-/- mice receiving no cell transfers, naïve CD4+ T cells alone, or purified wild type Tregs served as controls (n= 6/group). Recipient mouse body weights were monitored weekly for each group.",
    "ncbi_link": "Foxp3: 20371
Rag2: 19374"
  },
  {
    "caption": "PKA activity after overexpression of SPATC1L or SPATC1LΔC. Graphs show the average PKA activity of Spatc1l-transfected cells (white bar) and Spatc1lΔC-transfected cells (black bar) in the presence or absence of cAMP, expressed relative to control cells (mock) as a percentage. Representative signals observed in the assay are shown above. The overexpression of SPATC1L was confirmed in every experiment by immunoblotting (data not shown).",
    "ncbi_link": "Spatc1l: 76573
SPATC1L: 76573"
  },
  {
    "caption": "The amount of Cα associated with RIα in the presence or absence of SPATC1LΔC. After IP of RIα in cells overexpressing SPATC1LΔC or control, immunoblot analysis was performed using anti-Cα antibody. Graph shows densitometric analysis of Cα in relation to immunoprecipitated RIα in immunoblot analysis . In, input; IgG, immunoglobulin G from normal rabbit serum.",
    "ncbi_link": "SPATC1L: 76573"
  },
  {
    "caption": "PCR genotyping analysis of WT (Spatc1l+/+), heterozygous (Spatc1l+/-) and homozygous (Spatc1l-/-) mice.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "SPATC1L expression levels in testes obtained from WT, Spatc1l+/-, and Spatc1l-/- mice. An anti-GAPDH antibody was used as a control. Graph shows densitometric analysis of SPATC1L in relation to GAPDH in immunoblot analysis.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Percentage of females that became pregnant after mating with WT (white bar), Spatc1l+/- (gray bar), and Spatc1l-/- (black bar) male mice. Male mice used: WT, n = 5; Spatc1l+/-, n = 6; Spatc1l-/-, n = 7. WT female mice used for mating with the indicated genotype: WT, n = 30; Spatc1l+/-, n = 36; Spatc1l-/-, n = 42. Vaginal plugs were observed in all mated females.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Average litter size of pups produced by females mated with WT (white bar), Spatc1l+/- (gray bar), and Spatc1l-/- (black bar) male mice.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Macroscopic appearance of adult testes from an 8-week-old WT (Spatc1l+/+), heterozygous (Spatc1l+/-) and homozygous (Spatc1l-/-) mice. Scale bar = 2 mm.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Comparison of testis weight in WT (white bar), Spatc1l+/- (gray bar), and Spatc1l-/- (black bar) mice. The organs were trimmed of fat and weighed. The average testis weight/body weight ratios for WT, Spatc1l+/-, and Spatc1l-/- males were 0.0034±0.0001, 0.0038±0.0003, and 0.0031±0.0002, respectively. Data are presented as means ± s.d. (n = 7).",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Macroscopic appearance of the adult epididymis from WT, Spatc1l+/-, and Spatc1l-/- mice. Scale bar = 2 mm.",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Epididymis weight in WT (white bar), Spatc1l+/- (gray bar), and Spatc1l-/- (black bar) mice. The average epididymis weight/body weight ratios for WT, Spatc1l+/-, and Spatc1l-/- males were 0.001±0.0001, 0.001±0.0001, and 0.001±0.00008, respectively. Data are presented as means ± s.d. (n = 7).",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Number of mature epididymal sperm from WT (white bar), Spatc1l+/- (gray bar), and Spatc1l-/- (black bar) mice. Sperm were collected from the vas deferens. The average number of mature sperm in WT, Spatc1l+/-, and Spatc1l-/- males was (4.06 ± 0.40) × 106, (3.7 ± 0.7) × 106, and (3.93 ± 0.90) × 106, respectively. Data are presented as means ± s.d. (n = 5).",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Percentage of headless sperm from cauda epididymides of WT (black), Spatc1l+/- (gray), and Spatc1l-/- (white) mice. The average percentage of headless sperm in WT, Spatc1l+/-, and Spatc1l-/- males was 6.3, 52.9 and 100, respectively. Each dot represents percentage of headless sperm in an individual mouse, and medians are represented as horizontal lines. (n=13, *P < 0.001, Student's t-test).",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Morphological analyses of Spatc1l-KO epididymal sperm by SEM. Sperm were obtained from the vas deferens of 8-week-old WT (Spatc1l+/+) and KO (Spatc1l-/-) mice. Sperm neck regions are magnified in lower panels. AC, acrosomal cap; MP, mid piece; BP, basal plates. Scale bar = 2 μm (upper) and 0.5 μm (lower).",
    "ncbi_link": "Spatc1l: 76573"
  },
  {
    "caption": "Immunoblot analyses of five candidate proteins in testis (E) and sperm (F) of WT and KO mice. Anti-GAPDH, anti-ADAM2, and anti-α-tubulin antibodies were used as controls. Loss of SPATC1L in KO testis was confirmed by immunoblotting with anti-SPATC1L antibody.",
    "ncbi_link": "SPATC1L: 76573"
  },
  {
    "caption": "The amount of CAPZB in mock and Spatc1lΔC-transfected cells. Anti-GAPDH antibody was used as control. Overexpression of SPATC1L in TM4 cells was confirmed by immunoblotting with anti-SPATC1L antibody. Graph shows densitometric analysis of CAPZB in pcDNA3.1 vector-transfected control cells (mock; white bar) and SPATC1LΔC-transfected cells (black bar), expressed relative to control cells (mock) as a percentage. The density of CAPZB in immunoblot analysis was calculated in relation to density of GAPDH.",
    "ncbi_link": "Spatc1l: 76573
SPATC1L: 76573"
  },
  {
    "caption": "Phosphorylation of CPAZB3 in the presence or absence of SPATC1L. Phosphorylation of purified CAPZB3 was labeled with 32P via PKA in the presence or absence of SPATC1L, and estimated by autoradiography. The amount of CAPZB3 protein was quantified by Coomassie Brilliant Blue (CBB) staining (lower). Graph shows densitometric analysis of phopho-CAPZB3 (p-CAPZB3) in reactions without (control; white bar) or with SPATC1L (black bar), expressed relative to control as a percentage.",
    "ncbi_link": "SPATC1L: 76573"
  },
  {
    "caption": "Observation of filamentous actin (F-actin) in the presence (lower) or absence (upper) of SPATC1L. F-actin in pEGFP vector-transfected control cells (mock; upper, green) and cells overexpressing SPATC1LΔC (lower, green) was visualized by staining using Phalloidin (red). White bar shows the length of transfected cell. Scale bar = 50 μm.",
    "ncbi_link": "EGFP: 
SPATC1L: 76573"
  },
  {
    "caption": "The length of cell overexpressing SPATC1LΔC compared with control. Graph shows the average of measured cell length in pEGFP vector-transfected control cells (mock; white bar) and Spatc1lΔC-transfected cells (black bar), expressed relative to control cells (mock) as a percentage.",
    "ncbi_link": "EGFP: 
SPATC1L: 76573
Spatc1l: 76573"
  },
  {
    "caption": "Cell surface H2-Kb levels of wild type and TAP1-/- BMDC transduced with control vector or a vector expressing hβ2m were analyzed.",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Cross-presentation of OVA by wild type and TAP1-/- BMDC expressing hβ2m were compared to control BMDC, by measuring IL-2 production by a Kb-SIINFEKL specific T-cell hybridoma (B3Z) cultured with paraformaldehyde fixed BMDC that were incubated with varying numbers of OVA-coated latex beads for 6hr, prior to fixation.",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "The effect of hβ2m on the presentation of peptides derived from endogenous antigen was assessed by measuring IL-2 levels in the culture supernatant of the B3Z hybridoma incubated with fixed VV-OVA infected WT and TAP1-/- BMDC transduced with control vector or hβ2m.",
    "ncbi_link": "OVA: 
β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry.",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry.",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Surface H2-Kb levels of wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed by flow cytometry.",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "Cross-presentation of OVA by wild-type and TAP1-/- BMDC co-expressing Rab mutants and hβ2m were analyzed and IL-2 release is shown",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "TAP1-/- BMDC transduced with vector control (A) or hβ2m (C) were incubated with varying concentrations of Epoxomicin for 6hr in absence or presence of exogenously added Kb-binding SIINFEKL peptide and analyzed for surface expression of Kb by flow cytometry. Representative plots are shown (A, C). The impact of Epoxomicin on cell surface Kb was analyzed by plotting Kb surface expression on cells incubated with Epoxomicin, normalized to that on cell incubated without Epoxomicin (n=3) (B, D).",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "The effect of Epoxomicin on cross-presentation of OVA-coated beads by TAP1-/- BMDC expressing hβ2m was determined by incubating the BMDC with OVA coated latex beads in the presence of varying doses of Epoxomicin and 10μM gB peptide. After 6hrs the cells were fixed, incubated with B3Z cells and IL-2 production was measured",
    "ncbi_link": "β2m: 567
TAP1: 21354"
  },
  {
    "caption": "293T-FcR-Kb cells co-expressing empty vector or Rab mutants (Rab5ACA, Rab22ACA, Rab7ADN) individually, with either LacZ as a control or US6 were analyzed for cross-presentation of OVA using B3Z cells. The effects of US6 on cross-presentation were analyzed by plotting the mean percentage of IL-2 release by cells co-expressing US6 (A) with control vector or Rab mutants compared to cells co-expressing LacZ with control vector or Rab mutants, respectively.",
    "ncbi_link": "LacZ: 
Rab22A: 57403
Rab5A: 5868
Rab7A: 19349
US6: 3077555"
  },
  {
    "caption": "293T-FcR-Kb cells co-expressing empty vector or Rab mutants (Rab5ACA, Rab22ACA, Rab7ADN) individually, with either LacZ as a control or ICP47 (B), were analyzed for cross-presentation of OVA using B3Z cells. The effects of ICP47 on cross-presentation were analyzed by plotting the mean percentage of IL-2 release by cells co-expressing ICP47 (B) with control vector or Rab mutants compared to cells co-expressing LacZ with control vector or Rab mutants, respectively.",
    "ncbi_link": "LacZ: 
Rab22A: 57403
Rab5A: 5868
Rab7A: 19349
ICP47: 2703441"
  },
  {
    "caption": "293T-FcR-Kb cells expressing Rab5ACA were incubated with opsonized OVA coated latex beads in the presence of varying doses of Epoxomicin. After 6hrs the cells were fixed, incubated with B3Z cells and IL-2 production was measured.",
    "ncbi_link": "Rab5A: 5868"
  },
  {
    "caption": "293T-FcR-Kb cells expressing Rab22ACA were incubated with opsonized OVA coated latex beads in the presence of varying doses of Epoxomicin. After 6hrs the cells were fixed, incubated with B3Z cells and IL-2 production was measured.",
    "ncbi_link": "Rab22A: 57403"
  },
  {
    "caption": "293T-FcR-Kb cells expressing Rab7ADN (E) were incubated with opsonized OVA coated latex beads in the presence of varying doses of Epoxomicin. After 6hrs the cells were fixed, incubated with B3Z cells and IL-2 production was measured.",
    "ncbi_link": "Rab7A: 19349"
  },
  {
    "caption": "EM micrographs of double immuno-gold labeling using antibodies against immunoproteasome subunit LMP2 and the endolysosomal membrane marker LAMP1 in BMDC, WT MEF and LMP2 KO MEF. Large gold particles (15 nm, black arrow head) labels LMP2 and small gold particles labels LAMP1 (5 nm, white arrow head) (Scale bars = 500nm). The insets are the magnification of region of interest containing LAMP1 positive vacuole (Scale bars = 100nm), marked by the black rectangle.",
    "ncbi_link": "LMP2: 16912"
  },
  {
    "caption": "BMDC transduced with genes encoding GFP, GFP-Rab5ACA and GFP-Rab22ACA under the control of an inducible promoter were fixed and stained for LMP2 and LAMP1 and analyzed by confocal microscopy 24hr after doxycycline induction and 4hr after Alexa 647-OVA coated bead uptake. A single optical section of 10 optical sections of a representative cell are shown (Scale Bar 10μm). Region of interest containing LAMP1 positive vacuole containing beads coated with Alexa-647 conjugated OVA, marked by white rectangles, are magnified as inset (Scale bars = 1μm)",
    "ncbi_link": "GFP: 
Rab22A: 57403
Rab5A: 5868"
  },
  {
    "caption": "BMDC transduced with genes encoding GFP, GFP-Rab5ACA and GFP-Rab22ACA under the control of an inducible promoter were fixed and stained for LMP2 and LAMP1 and analyzed by confocal microscopy 3D-rendering of 10 optical sections of a representative cell are shown (Scale Bar 10μm). Region of interest containing LAMP1 positive vacuole containing beads coated with Alexa-647 conjugated OVA, marked by white rectangles, are magnified as inset (Scale bars = 1μm)",
    "ncbi_link": "GFP: 
Rab22A: 57403
Rab5A: 5868"
  },
  {
    "caption": "BMDC co-expressing LMP2-RFP and GFP-Rab5ACA were live imaged 16hr after doxycycline induction and 30min post uptake of Alexa647 coated latex beads (Bar 10μm). Images were acquired every 3min and images taken at 12min interval are presented (I-K). The arrowheads in panel (I and J) mark the phagosome or vacuoles containing LMP2, respectively.",
    "ncbi_link": "GFP: 
RFP: 
LMP2: 16912
Rab5A: 5868"
  },
  {
    "caption": "BMDC co-expressing LMP2-RFP and GFP-Rab22ACA (J, K) were live imaged 16hr after doxycycline induction and 30min post uptake of Alexa647 coated latex beads (Bar 10μm). Images were acquired every 3min and images taken at 12min interval are presented (I-K). The arrowheads in panel (I and J) mark the phagosome or vacuoles containing LMP2, respectively. The boxed region in panel (J) marks a phagosome that has been enlarged in panel (K) (Bar 1μm).",
    "ncbi_link": "GFP: 
RFP: 
LMP2: 16912
Rab22A: 57403"
  },
  {
    "caption": "Ubiquitination of phagosomal cargo within the phagosomes was assessed by measuring the acquisition of GFP fluorescence by phagocytosed latex beads conjugated with OVA post-detergent extraction from BMDC expressing GFP or GFP-Ub (D). The mean of fluorescence intensities of GFP on the beads from independent experiments was plotted (E).",
    "ncbi_link": "GFP: 
Ub: "
  },
  {
    "caption": "B. Differentiation of Atf1-/-, Fos-/-Jun-/-, Foxj2-/-, Meis3-/-, Nr5a2-/-, Sp1+/- and Zfp354c-/- mESCs in the 3KI background to ectoderm. C. Differentiation of Atf1-/-, Fos-/-Jun-/-, Foxj2-/-, Meis3-/-, Nr5a2-/-, Sp1+/- and Zfp354c-/- mESCs in the 3KI background to mesendoderm. D. Differentiation of Atf1-/-, Fos-/-Jun-/-, Foxj2-/-, Meis3-/-, Nr5a2-/-, Sp1+/- and Zff354c-/- mESCs in the 3KI background to definitive endoderm.",
    "ncbi_link": "Atf1: 11908
Fos: 14281
Foxj2: 60611
Jun: 16476
Meis3: 17537
Nr5a2: 26424
Sp1: 20683
Zfp354c: 30944
Zff354c: 30944"
  },
  {
    "caption": "F. Differentiation of wild type (WT), Sp1+/-, Nr5a2-/- and Fos-/-Jun-/- mESCs in the 3KI background to definitive endoderm.",
    "ncbi_link": "Fos: 14281
Jun: 16476
Nr5a2: 26424
Sp1: 20683"
  },
  {
    "caption": "(c) LC3B was immunoprecipitated (IP) from FAK+/+ and FAK−/− cells and then immunoblotted with anti-Src, anti-pTyr-416-Src and anti-LC3B antibodies.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(d) Cells were transfected with 40 nM scrambled, Atg5 or Atg12 siRNA for 72 h and immunoblotted with anti-Atg5, anti-Atg12 and anti-actin antibodies (lower panels) or fixed and stained for anti-pTyr-416-Src (green), anti-paxillin (red) and with DAPI (blue). Dashed arrows point to intracellular phospho-Src-containing puncta; solid arrows point to peripheral phospho-Src. Scale bars, 20 μm. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "Atg12: 67526
Atg5: 11793"
  },
  {
    "caption": "(a) Top, cells were transiently transfected with an RFP-GFP tandem fluorescent-tagged LC3 (RFP-GFP-LC3). Scale bars, 20 μm. Bottom, the number of yellow puncta and the number of RFP LC3-positive puncta in the merged images were counted and the total number of puncta per cell was calculated. Data are presented as mean±s.d. (n=3).",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(a) Top, FAK−/− cells were treated with 200 nM dasatinib for 24 h and then fixed and stained for anti-Src antibody (green). Solid arrows indicate Src at the cell periphery; dashed arrows indicate Src in autophagosomes. Scale bars, 20 μm. Bottom, quantification of dasatinib-treated cells with Src in puncta. Data are presented as mean±s.d. and significance is P0.001 (n=3). Middle, lysates from cells treated with dasatinib were immunoblotted with anti-Src and anti-pTyr-416-Src and lysates from cells treated with dasatinib and chloroquine were immunoblotted with anti-LC3B and anti-actin antibodies. Densitometry was carried out to calculate the increase in the amount of LC3B-II relative to actin for each condition after treatment with chloroquine and is presented as a percentage increase for the immunoblot shown.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(b) Top, FAK−/− cells were transiently transfected with SrcY527F-GFP or with Src-251-GFP (green) and stained for anti-LC3B (red). Scale bars, 20 μm. Bottom, quantification of cells with co-localization between Src and LC3B. Data are presented as mean±s.d. and significance is P0.001 (n=3).",
    "ncbi_link": "FAK: 14083
Src: 20779"
  },
  {
    "caption": "(c) Left, FAK−/− cells stably re-expressing wild-type FAK, FAKY397F or FAKY4F-Y9F were fixed and stained for anti-FAK (red) and anti-pTyr-416-Src (green). Solid arrows indicate co-localization at adhesions and dashed arrows indicate active Src in autophagosomes. Scale bars, 20 μm. Right, lysates from these cells were also immunoblotted with anti-FAK and anti-actin antibodies.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(d) Left, wild-type FAK, FAKY397F or FAKY4F-Y9F cells were transfected with RFP-GFP-LC3. Solid arrows indicate co-localization and dotted arrows indicate its absence. Scale bars, 20 μm.",
    "ncbi_link": "LC3: 67443///66734
FAK: 14083"
  },
  {
    "caption": "(b) Top, wild-type FAK and FAK−/− cells were transiently transfected with two individual Atg5 shRNAs (1 and 2), selected in puromycin and then the clonogenic assay was carried out as described above. Bottom, quantification; data are presented as mean±s.d. and significance is P>0.1 for Atg5 A and B in wild-type FAK cells and P0.01 for Atg5 A and P0.05 for Atg5 B in FAK−/− cells (n=3).",
    "ncbi_link": "Atg5: 11793
FAK: 14083"
  },
  {
    "caption": "(c) Cells were also stained with TUNEL. The positive control was DNase1-treated cells and the negative control lacked TUNEL reaction mix. Quantification is shown and data are presented as mean±s.d. and significance is P0.005 for 3-MA and P0.001 for Atg5 siRNA (n=3).",
    "ncbi_link": "Atg5: 11793
DNase1: 13419"
  },
  {
    "caption": "(d) FAK−/− cells were untreated or treated with dasatinib, 3-MA, chloroquine or bafilomycin A (BFA) for 24 h, or were transfected with scrambled or Atg5 siRNA for 72 h and then immunoblotted with an anti-PARP antibody. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(b) c-Cbl was immunoprecipitated (IP) from FAK+/+ and FAK−/− cells and then immunoblotted with anti-Src, anti-pTyr-416-Src and anti-c-Cbl antibodies.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(c,d) Cells were transfected with scrambled siRNA or with c-Cbl siRNA for 72 h and then immunoblotted with anti-c-Cbl and actin antibodies (c) or stained for anti-pTyr-416-Src (red) and anti-c-Cbl (green; d, left). Dashed arrows indicate co-localization and solid arrows indicate Src at focal adhesions. Scale bars, 20 μm. Quantification is shown (d, right). Data are presented as mean±s.d. and significance is P>0.5 for FAK+/+ cells and P0.001 for FAK−/− cells (n=3).",
    "ncbi_link": "c-Cbl: 12402
FAK: 14083"
  },
  {
    "caption": "(e) LC3B was immunoprecipitated from FAK−/− cells expressing either scrambled or c-Cbl siRNA and then immunoblotted with anti-Src and anti-LC3B antibodies. Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "c-Cbl: 12402"
  },
  {
    "caption": "(a) c-Cbl siRNA was transfected into FAK−/− cells expressing siRNA resistant, HA-tagged wild-type c-Cbl or c-Cbl mutants with defective E3 ligase activity (c-CblC381A or c-Cbl-70Z). Left, cells were stained for anti-p-Tyr-416-Src (green), anti-HA (red) and with DAPI (blue). Solid arrows show co-localization in intracellular puncta. Scale bars, 20 μm. Right, quantification of percentage of cells that contained active Src in intracellular puncta. Data are presented as mean±s.d. and significance is P>0.5 (n=3).",
    "ncbi_link": "c-Cbl: 12402"
  },
  {
    "caption": "(c) GST-pulldown assay of HA-tagged wild-type c-Cbl, c-CblAA (W802A, L805A) and c-CblAAAA (W802A, L803A, S804A, L805A) expressed in HEK293T cells was carried out using GST-LC3.",
    "ncbi_link": "c-Cbl: 12402"
  },
  {
    "caption": "(d) c-Cbl siRNA was transfected into FAK−/− cells expressing siRNA-resistant HA-tagged wild-type c-Cbl or c-CblAAAA. Left, cells were stained for anti-pTyr-416-Src (green), anti-HA (red) and with DAPI (blue). Solid arrows indicate pTyr-416 localization to adhesions and dashed arrows indicate localization to intracellular puncta. Scale bars, 20 μm. Right, quantification of percentage of cells that contained active Src in intracellular puncta. Data are presented as mean±s.d. and significance is P0.01 (n=3). Uncropped images of blots are shown in Supplementary Fig. S9.",
    "ncbi_link": "c-Cbl: 12402"
  },
  {
    "caption": "B. Blots showing expression of hTauAT (hTau, Mr ~67 kDa) and/or endogenous mouse Tau (mTau, Mr ~45-55 kDa) in the hippocampus of 10 month old heterozygous (+/-) and homozygous (+/+) hTauAT mice in comparison to age matched control (Ctrl) detected by pan-Tau antibody K9JA. Actin at 42 kDa serves as loading control.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Quantification of (B). Ratio of hTau / mTau indicating a higher hTauAT -expression in homozygous mice (~1.8) compared to heterozygous mice (~1.0). Each bar represents an average of n=4 animals, error bars represent SEM.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "D. Quantification of mRNA levels in hippocampi of heterozygous and homozygous hTauAT 16 month old mice (n = 4 per group).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "E. Distribution of hTauAT visualized by the human Tau specific antibody HT7 in the hippocampal CA3-region of hetero- and homozygous hTauATmice at the age of 14 month. Notice the mis-sorted hTauAT in cell bodies and dendrites (arrowheads) of pyramidal neurons of the CA3 region and immunreactivity of the axons (mossy fibers, asterisks). By contrast the control shows no immunoreactivity.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "F. Elevated hTauAT -expression causes Tau-pathology inside area CA3 of the hippocampus. Note the increase in Tau phosphorylation probed with the antibody against pT217, a site upstream of the repeat domain. Arrowheads point to areas with phosphorylated and mislocalized Tau in cell somata of pyramidal neurons in area CA3.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "H. Antibody PHF-1 (phosphorylation sites pSer396+pSer404) illustrates pathological phosphorylation of Tau due to hTauAT expression especially in stratum lucidum (asterisks) of area CA3 and pyramidal neuroncell bodies (arrows).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "B. Tau aggregation confirmed by Gallyas silver staining of NFTs bearing neurons in hetero- and homozygous hTauAT mice at 14 month of age compared to non-reactive control littermate mice. In homozygous hTauAT mice the extent of neurofibrillary tangles (NFTs) visualized by Gallyas silver staining is enhanced compared to heterozygous hTauAT mice (white arrowheads). The control shows no silver-reactive Tau aggregates.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Western blot analysis using the pan-Tau antibody K9JA indicates sarcosyl-insoluble Tau species of human hTauAT (upper band) and mouse Tau (mTau, lower band). Note the enhanced Tau aggregation in homozygous hTauAT mice compared to heterozygous hTauAT mice and control mice.D. Quantification of (C). The ratio of hTauAT /mTau indicates a stronger aggregation in the homozygous hTauAT mice (~1.4) compared to heterozygous hTauAT mice (~0.7 (n=4 animals, error bars represent SEM).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Western blot analysis with pan-Tau K9JA antibody to estimate expression levels of hTauAT and endogenous Tau (mTau). Slice homogenates from non-transgenic littermate (lane 1, Ctrl), heterozygouse hTauAT (lane 2, (+/-)) or homozygouse hTauAT slices (lane 3, (+/+)) were analyzed after three weeks in culture. Actin served as a loading control.B. Quantification of hTauAT expression levels (n=3-6 slice homogenates). The ratio between hTauAT and endogenous mouse Tau is shown.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Immunohistochemistry with antibodies against human Tau (TauY9 antibodies; middle panel) and dendritic marker MAP2 (left panel) in slice cultures at DIV 10. Stratum radiatum of area CA3 is shown. Although MAP2 staining is apparent, no signal is detected by the TauY9 antibody in control slices. In contrast, in hTauAT slices human Tau is detected in both dendrites and axons (see asterisk in merged image).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "D. Immunohistochemistry against phosphorylated Tau at the PHF1-epitope in area CA3 of a control (upper lane) or hTauAT slice (bottom lane). PHF1 staining is slightly visible in some axons in control slices. In contrast, PHF1-phosphorylated Tau is apparent in somata, dendrites and axons of neurons in hTauAT slice cultures.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "E. Higher magnification image of apical dendrites in area CA3 in a hTauAT slice after immunohistochemistry against MAP2 (red) and Tau (K9JA antibody, green). Tau staining is seen in dendritic spines (asterisks) in contrast to MAP2, which is restricted to the dendritic shaft.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Slices (DIV15) from control mice were loaded with the Ca++ sensitive dye Fura-2AM. Ratiometric images are presented at baseline and after application of high potassium. Note the increase in intracellular Ca++ ([Ca++]i) after KCl application.B. Slices (DIV15) from hTauAT mice were loaded with the Ca++ sensitive dye Fura-2AM. Ratiometric images at baseline and after application of high potassium in area CA3 are depicted. Note the increase in [Ca++]i (false color legend) under both conditions in hTauAT slices compared to controls.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Electrophysiological example traces (control = black; hTauAT = red) of excitatory postsynaptic field potentials (fEPSP) depicts examples of depolarizations that are induced by a single high potassium chloride application in stratum pyramidale (s.p.) of area CA3 in slices in which calcium imaging experiments were conducted. The example depolarization evokes averaged calcium influxes into neurons depicted in the calcium imaging graph. The graph shows the mean of [Ca++]i changes in response to high KCl in stratum radiatum and stratum pyramidale of area CA3 in Fura2-AM loaded hippocampal slices. After depolarization [Ca++]i rises up to ~600 nM in hTauAT slices (red trace, n=6 slices, prepared from at least three animals), compared to ~300 nM in control slices (black trace, n=6 slices; prepared from at least three animals). Note that even under resting conditions [Ca++]i is elevated to ~120nM due to hTauAT expression.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Glutamate content in the culture medium ([Glu]e) from either hTauAT (n=10 culture inserts containing 6 slices each) or control slices (n=5-12 culture inserts) analyzed at DIV 5, 10, 20 and 25. Glutamate content from medium cultured with hTauAT slices is shown in percent of control at each time point. Increased levels were observed between DIV 5 and DIV 20. At DIV 25 glutamate levels already declined to control levels. One-way ANOVA followed by Tukey's post-hoc test *p<0.05; **p<0.01 ***p<0.001.B. Lactate dehydrogenase (LDH) release (a measure of cytotoxicity) analyzed in hTauAT (n=17-19 culture inserts containing 6 slices each) or control slices (n=15-16 culture inserts) at DIV 5, 10, 20 and 25. LDH release of hTauAT slices is shown in percent of control at each time point. A pronounced increase (~25%) in LDH release was observed due to hTauAT expression starting at DIV 10 but not at DIV 5 One-way ANOVA: *p<0.05; **p<0.01 and ***p<0.001.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Slice cultures from control (left), hTauAT (middle) or hTauAT treated with ceftriaxone (CEF; 100 µM; right) stained against neuronal nuclear protein (NeuN) at DIV 30. Representative neuronal cell layers are shown. hTauAT slices show neuronal loss in the granular cell layer of the dentate gyrus and the pyramidal cell layer in the region of the hilus in area CA3 (middle panel, red arrows). Treatment with ceftriaxone for 30 days prevents neuronal loss in DG and area CA3.D. NeuN positive cell bodies were counted in the DG and within the pyramidal cell layer in area CA3 and CA1 at DIV 30 in defined regions of interest (ROI). The number of neurons was reduced in hTauAT slices, both within area DG and CA3, whereas the number of neurons in the CA1 was only slightly affected. Neuronal loss was largely prevented in cultures treated with ceftriaxone (CEF) in dentate gyrus and area CA3 (n=14-19 slices per group and area; prepared from at least 6 animals). One-way ANOVA followed by Tukey's post-hoc test *p<0.05; **p<0.01",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Representative microphotograph of spines on dendrites from control littermate mice at the age of 12 months. Apical dendrites from CA3pyramidal neurons are visualized by Golgi staining. The contrast of photomicrographs was inverted.B. Dendritic spines from heterozygous hTauATmice, seen by Golgi staining.C. Quantification of dendritic spine densities in control littermate and hTauAT mice. Note that the spine density in heterozygous hTauAT is increased (control littermates: n = 2 animals; heterozygous hTauATn = 4 animals; an average of 5 dendrites of CA3pyramidal neurons were analyzed per animal; unpaired t-test).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "D. Input / output curve of field potential recording in the mossy fiber pathway in acute slices of 12±1 month old mice demonstrating significantly enhanced basal synaptic transmission (Multiple repeat ANOVA,F(9, 126)=2.00, p=0.044) in area CA3 in mice expressing hTauAT. Scale bars: 500 µV vertical bar and 20 msec horizontal bar.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "E. Long-term potentiation in the mossy fiber pathway demonstrates no differences in long-term plasticity between control (black) and hTauAT expressing mice (red).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "F. Input / output curve of field potential recording in stratum pyramidale (s.p.) of area CA3 in organotypic hippocampal slices at DIV 30. Somatic field potentials are increased in hTauAT compared to control littermates. Scale bars: 800 µV vertical bar and 20 msec horizontal bar.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Example of electrophysiological fEPSP recording in stratum pyramidale of area CA3 in a control slice (DIV30) during wash-in of 50 µm picrotoxin. This leads to blockage of GABAergic transmission followed by epileptiform discharges (burst) occurring approximately after 3 min. The zoom-in reveals that such an epileptiform discharge (burst) consists of repetitive firings.B. Similar example trace as in (A) recorded in a hTauAT expressing slice (red) demonstrating an increase in burst frequency as well as in firings per burst due to hTauAT expression.C. Quantification of bursts per minute in DIV 10 slices from control littermates and hTauAT slices demonstrating a ~2-fold increase in hTauAT slices (n=8 slices per group).D. Firings per burst are increased ~1.5-fold already at the early time point DIV10 due to hTauAT expression.E. Analysis of burst frequency in slices at DIV 30 demonstrates the progression of the pathological effect beyond that observed at DIV 10. Burst frequency is enhanced in hTauAT expressing slices (n = 10 slices). If Ceftriaxone (CEF) is applied to hTauAT slices the pathological burst frequency enhancement is partly prevented (n = 5 slices).F. Firings per burst are strongly enhanced due to hTauAT expression in slices at DIV 30. Ceftriaxone prevents this pathological phenotype if applied during the entire period of cultivation (n = 6 slices).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "G. Example of a control littermate organotypic slice culture at DIV 24 stained against NeuN (red) and pan-Tau (K9JA antibody, green). Axonal projections (green) of granule cells (red) in the dentate gyrus are depicted.H. Hippocampal slice culture expressing hTauAT stained against NeuN (red) and pan-Tau (green) showing mossy fiber sprouting in the hilar region, CA3 and dentate gyrus (white arrows).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "A. Quantification of glutamate concentrations in the medium of control and hTauAT cultures in the presence of either 50 nM tetanus neurotoxin (TeNT) or 1 µM tetrodotoxin (TTX) at DIV5. Under both conditions, glutamate levels in the culture medium of hTauAT slices decreased to control levels (n=6 culture inserts containing 6 slices each / group and condition).B. Quantification of extracellular glutamate concentrations in culture medium of either control or hTauAT slices at DIV 20 in the presence or absence of 50 µM benzyloxy-aspartic acid (TBOA) from DIV1-DIV20 demonstrating a possible contribution of astrocytic glutamate dysregulation to increased extracellular glutamate in hTauAT slices (n=8-9 culture inserts containing 6 slices each / group and condition). One-Way ANOVA F(3,30)=14,89; p<0.001",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "C. Quantification of LDH release into the culture medium of either control or hTauAT slices at DIV 20 in the presence or absence of 50 µM benzyloxy-aspartic acid (TBOA) from DIV 1 to DIV 20 (n=6-12 culture inserts containing 6 slices each / group and condition). One-Way ANOVA followed by Tukey's post-hoc test.",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "D. Quantification of extracellular glutamate concentrations in either control or hTauAT cultures treated (n=7-8 culture inserts containing 6 slices each / group and condition) with ceftriaxone from DIV 1 to DIV 25 demonstrating the preventative effect of CEF on the increase in extracellular glutamate in hTauAT slices. One-Way ANOVA F(3,25)=9.075; p=0.0003).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "E. LDH release at DIV 25 is strongly reduced due to long term treatment with ceftriaxone in hTauAT slice cultures (n=8-10 culture inserts containing 6 slices each / group and condition). One Way ANOVA F(3,32)=7.685; p=0.0005).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "F. Intracellular calcium rise after KCl stimulation is not distinguishable from control slices in hTauAT slices treated with ceftriaxone for 15 days (n=5-9 slices; prepared from at least three animals). One way ANOVA F((3,25)=7.317; p=0.0011).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "Confirmation of RNA-seq data via qPCR on pure hepatocytes isolated via flow cytometry-based sorting (n = 3/group). (E) Ppara and (F) Hmgcs2 mRNA expression is shown as relative expression, normalized to housekeeping genes Hprt and Rpl. P-values were calculated using 2-way ANOVA analysis.",
    "ncbi_link": "Hprt: 
Rpl: 
Hmgcs2: 15360
Ppara: 19013"
  },
  {
    "caption": "Mice (n = 4/group, data are representative of 2 experiments) underwent a sham (with or without starvation) or CLP operation and liver was isolated on several timepoints post-surgery for RNA preparation and qPCR. Ppara mRNA expression is shown as relative expression, normalized to housekeeping genes Hprt and Rpl. P-values were calculated using 1-way ANOVA analysis.",
    "ncbi_link": "Hprt: 
Rpl: 
Ppara: 19013"
  },
  {
    "caption": "Pearson correlation between log fold change (LFC) Ppara expression levels and body temperature 24h post-sepsis (n= 38, r = 0.6875, combined data of 4 independent experiments).",
    "ncbi_link": "Ppara: 19013"
  },
  {
    "caption": "Liver Hmgcs2 mRNA expression at different timepoints post-sepsis, expression is shown as relative expression, normalized to housekeeping genes Hprt and Rpl. P-values were calculated using 1-way ANOVA analysis (n = 4/group, data are representative of 2 experiments).",
    "ncbi_link": "Hprt: 
Rpl: 
Hmgcs2: 15360"
  },
  {
    "caption": "Mice were pre-treated with Pemafibrate (1mg/kg) or vehicle (0,9% NaCl) for 1 week before being subjected to CLP. Liver samples were isolated 24h after CLP (n= 5-7/group, combined data of 2 independent experiments), mRNA was prepared and gene expression levels of Ppara was analyzed via qPCR. Gene expression values are shown as relative expression, normalized to housekeeping genes Hprt and Rpl. P-values were calculated via 2-way ANOVA test.",
    "ncbi_link": "Hprt: 
Rpl: 
Ppara: 19013"
  },
  {
    "caption": "Dynamic fluorescence patterns according to cell density in 8×GTIIC-EmGFP 293T cells.",
    "ncbi_link": "EmGFP: "
  },
  {
    "caption": "EmGFP intensity in LATS2 knockdown, or forced expression of a constitutively active form of YAP (YAP-S127A). Scale bars indicate 100 μm.",
    "ncbi_link": "LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Scatter plots of mean frequency of each shRNA per gene. Average of v HOXA4 is indicated as a red dot.",
    "ncbi_link": "HOXA4: 3201"
  },
  {
    "caption": "Augmented 8×GTIIC-luciferase reporter activity by loss of HOXA4. ShSAV1 was used as an experimental control. **P<0.01 vs shCtrl, by ANOVA with Sidak's correction.",
    "ncbi_link": "HOXA4: 3201
SAV1: 60485"
  },
  {
    "caption": "Quantitative real-time PCR analysis of ANKRD1 expression in HEK 293T cells transfected with shHOXA4",
    "ncbi_link": "ANKRD1: 27063
HOXA4: 3201"
  },
  {
    "caption": "Quantitative real-time PCR analysis of ANKRD1 expression in HEK 293T cells transfected with HOXA4 expression vector",
    "ncbi_link": "ANKRD1: 27063
HOXA4: 3201"
  },
  {
    "caption": "Quantitative real-time PCR analysis of CTGF, CYR61, and BIRC5 in HEK 293T cells with knockdown of endogenous HOXA4. ShLATS1/2 and shYAP were used as an experimental control. *P<0.05, **P<0.01 vs shCtrl, by ANOVA with Sidak's correction.",
    "ncbi_link": "BIRC5: 332
CYR61: 3491
CTGF: 1490
HOXA4: 3201
LATS1: 9113
YAP: 10413"
  },
  {
    "caption": "8×GTIIC-luciferase reporter assays in HEK 293T cells transfected HOXA4 and/or shLATS1/2. **P<0.01 vs shCtrl, by two-way ANOVA with Sidak's correction.",
    "ncbi_link": "HOXA4: 3201
LATS1: 9113"
  },
  {
    "caption": "Quantitative real-time PCR analysis of HOXA4, YAP, CTGF, and CYR61 in HEK 293T cells with overexpression of HOXA4 and/or constitutive active form of YAP (YAP -5SA). *P<0.05, **P<0.01 vs YAP-5SA with LacZ, by ANOVA with Sidak's correction.",
    "ncbi_link": "LacZ: 
CYR61: 3491
CTGF: 1490
HOXA4: 3201
YAP: 10413"
  },
  {
    "caption": "Quantitative real-time PCR analysis of HOXA4, YAP, CTGF, and CYR61 in HEK 293T cells with knockdown of endogenous HOXA4 and/or overexpression of YAP-5SA. *P<0.05, **P<0.01 vs YAP-5SA with shCtrl, by ANOVA with Sidak's correction.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
HOXA4: 3201
YAP: 10413"
  },
  {
    "caption": "Association of HOXA4 with TEAD1 indicated by co-IP experiments. HEK 293T cells were co-transfected with FLAG-HOXA4 and Myc-TEAD1",
    "ncbi_link": "FLAG: 
Myc: 
HOXA4: 3201
TEAD1: 7003"
  },
  {
    "caption": "Association of HOXA4 but not YAP indicated by co-IP experiments. HEK 293T cells were co-transfected with FLAG-HOXA4 and Myc-YAP.",
    "ncbi_link": "FLAG: 
HOXA4: 3201
Myc: 17869
YAP: 10413"
  },
  {
    "caption": "Immunoprecipitation using FLAG antibody in lysates from HEK 293T cells transfected with plasmids expressing HOXA4 truncation mutants and TEAD1.",
    "ncbi_link": "HOXA4: 3201
TEAD1: 7003"
  },
  {
    "caption": "Immunoprecipitation using FLAG antibody in lysates from HEK 293T cells transfected with plasmids expressing TEAD1 truncation mutants and HOXA4. Arrowheads indicate IgG heavy chain. Arrows indicate TEAD1 (a.a. 1-426).",
    "ncbi_link": "HOXA4: 3201
TEAD1: 7003"
  },
  {
    "caption": "ChIP assays of CTGF and CYR61 promoters using TEAD4 or YAP antibodies in HEK 293T cells transfected with plasmids expressing HOXA4. *P<0.05, **P<0.01, by unpaired two-tailed Student's t-test. Data are expressed as the means ± SEM of three independent experiments.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
HOXA4: 3201"
  },
  {
    "caption": "Competitive co-IP assay and densitometry showing significantly reduced TEAD-YAP interaction by overexpression of HOXA4 in a dose-dependent manner in HEK 293T cells. *P<0.05, **P<0.01, by ANOVA with Sidak's correction. Data are presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "HOXA4: 3201"
  },
  {
    "caption": "Expression of Hoxa4 in various mouse tissues using qRT-PCR. Expression of glyceraldehyde-3-phosphate dehydrogenase (Gapdh) mRNA was used as an internal control. WAT; white adipose tissue, BAT; brown adipose tissue, Skm; skeletal muscle.",
    "ncbi_link": "Gapdh: 
glyceraldehyde-3-phosphate dehydrogenase: 
Hoxa4: 15401"
  },
  {
    "caption": "Quantitative real-time PCR analysis of smooth muscle specific genes in primary human VSMCs transduced with lentiviral vectors encoding overexpression or knockdown of HOXA4 and YAP. Cells infected with lentiviral vectors encoding LacZ or shCtrl were used as controls. *P<0.05, **P<0.01, by unpaired two-tailed Student's t-test.",
    "ncbi_link": "LacZ: 
HOXA4: 3201
YAP: 10413"
  },
  {
    "caption": "Representative western blotting analysis of total protein lysates of primary human VSMCs transduced with lentiviral vectors encoding knockdown of YAP/TAZ Representative western blotting analysis of total protein lysates of primary human VSMCs transduced with lentiviral vectors encoding knockdown of HOXA4.",
    "ncbi_link": "HOXA4: 3201
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "Representative western blotting analysis of total protein lysates of primary human VSMCs transduced with lentiviral vectors encoding knockdown of HOXA4 Representative western blotting analysis of total protein lysates of primary human VSMCs transduced with lentiviral vectors encoding knockdown of HOXA4.",
    "ncbi_link": "HOXA4: 3201"
  },
  {
    "caption": "Quantitative real-time PCR analysis of YAP/TEAD target genes in primary human VSMCs transduced with lentiviral vectors encoding overexpression or knockdown of HOXA4 and YAP. The cells infected with lentiviral vectors encoding LacZ or shCtrl were used as controls. *P<0.05, **P<0.01, by unpaired two-tailed Student's t-test.",
    "ncbi_link": "LacZ: 
HOXA4: 3201
TEAD: 21676
YAP: 10413"
  },
  {
    "caption": "Proliferation assay in VSMCs transduced with the indicated genes. Virus-transfected human VSMCs were plated at equal density in growth medium, and then cells were collected and counted at each time point as indicated. **P<0.01 vs LacZ, by ANOVA with Sidak's correction.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "BrdU incorporation assays in VSMCs transduced with the indicated genes. The percentage of BrdU positive cells in each group is shown. Nine to twelve images were randomly acquired and analyzed. **P<0.01 vs LacZ, by ANOVA with Sidak's correction.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "Representative western blotting analysis of total protein lysates of primary human VSMCs transduced with lentiviral vectors encoding shRNAs of HOXA4 and TEAD1/3/4. Quantification of alpha smooth muscle actin and calponin protein levels is expressed as the means ± SEM of three independent experiments. *P<0.05, **P<0.01, by ANOVA with Sidak's correction.",
    "ncbi_link": "HOXA4: 3201
TEAD1: 7003"
  },
  {
    "caption": "Representative immunoblotting images and quantification of the interaction between endogenous TEAD1 and HOXA4 or YAP using co-IP experiments in human VSMCs with knockdown of HOXA4. *P<0.05 vs shCtrl, by ANOVA with Sidak's correction. Data are presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "HOXA4: 3201"
  },
  {
    "caption": "ChIP assays of CTGF, CYR61 and α-SMA promoters using anti-FLAG-tag, anti-Myc-tag, anti-TEAD1 antibodies in human VSMCs transfected with plasmids expressing Myc-tagged YAP-5SA and/or FLAG-tagged HOXA4. *P<0.05, **P<0.01 vs FLAG-GFP, by unpaired two-tailed Student's t-test. Data are expressed as the means ± SEM of three independent experiments.",
    "ncbi_link": "FLAG: 
GFP: 
Myc: 
α-SMA: 59
CYR61: 3491
CTGF: 1490
HOXA4: 3201
YAP: 10413"
  },
  {
    "caption": "Quantitative real-time PCR analysis of differentiated smooth muscle marker genes in the left carotid artery of 8-week-old WT and Hoxa4 KO mice (WT: n=7, Hoxa4 KO: n=5).",
    "ncbi_link": "Hoxa4: 15401"
  },
  {
    "caption": "Quantitative real-time PCR analysis of differentiated smooth muscle marker genes in the ligated left carotid artery of WT and Hoxa4 KO mice at 1 week after ligation (n=6). Mean expression level of six WT mice at the baseline was defined as 1.0.",
    "ncbi_link": "Hoxa4: 15401"
  },
  {
    "caption": "Hoxa4 expression levels in the ligated left carotid artery of WT mice at 1 week after ligation (n=6).",
    "ncbi_link": "Hoxa4: 15401"
  },
  {
    "caption": "Quantitative real-time PCR analysis of Yap/Tead target genes in the left carotid artery of 8-week-old WT and Hoxa4 KO mice (WT: n=7, Hoxa4 KO: n=5).",
    "ncbi_link": "Hoxa4: 15401
Tead: 21676
Yap: 22601"
  },
  {
    "caption": "Quantitative real-time PCR analysis of Yap/Tead target genes in the ligated left carotid artery of WT and Hoxa4 KO mice at 1 week after ligation (n=6). Mean expression level of six WT mice at the baseline was defined as 1.0.",
    "ncbi_link": "Hoxa4: 15401
Tead: 21676
Yap: 22601"
  },
  {
    "caption": "Representative western blotting analysis and densitometry of non-ligated (right; R) and ligated (left; L) carotid arteries from WT and Hoxa4 KO mice at 1 week after ligation (WT: n=6, Hoxa4 KO: n=7). *P<0.05, **P<0.01, by two-way ANOVA with Sidak's correction.",
    "ncbi_link": "Hoxa4: 15401"
  },
  {
    "caption": "Representative images showing Elastica van Gieson staining (G), and vessel, neointima and media area (H), and neointima to media layer ratio (I) of carotid arteries of WT and Hoxa4 KO mice at 4 weeks after ligation (WT: n=14, Hoxa4 KO: n=11).",
    "ncbi_link": "Hoxa4: 15401"
  },
  {
    "caption": "(B) RNAs were extracted from the cell culture supernatant, and detected using a commercial kit targeting the ORF 1ab (red) and N (blue) genes of SARS-CoV-2.",
    "ncbi_link": "ORF 1ab: 
N: 43740575"
  },
  {
    "caption": "B Representative images of transduced adult-born neurons at 17dpi. CAG-dnLEF-IRES-GFP (dnLEF, green) and CAG-RFP (control, red) double transduced cells (arrows) and CAG-RFP single transduced cells (arrowheads). Scale bar= 20 µm",
    "ncbi_link": "GFP: 
IRES: 
LEF: 16842"
  },
  {
    "caption": "C Representative reconstructions of control and dnLEF neurons. Scale bar= 20 µm",
    "ncbi_link": "LEF: 16842"
  },
  {
    "caption": "D Analysis of morphology showed a reduction in dendritic length in dnLEF transduced neurons [p<0.0001], while the number of branch points remained comparable [p=0.7914]. Sholl analysis displayed a reduction in dendritic complexity in dnLEF transduced neurons and indicated decreased growth of terminal dendritic branches [p<0.0001] (control: n= 20 cells from 3 animals, dnLEF: n= 38 cells from 6 animals).",
    "ncbi_link": "LEF: 16842"
  },
  {
    "caption": "E DnLEF neurons displayed basal dendrites [p<0.0001] (control: n= 20 cells from 3 animals, dnLEF: n= 38 cells from 6 animals).",
    "ncbi_link": "LEF: 16842"
  },
  {
    "caption": "G Representative images depicting CAG-GFP-IRES-Cre transduced adult-born neurons in control and β-catex3 mice at 17dpi. Scale bar= 20µm",
    "ncbi_link": "Cre: 
GFP: 
IRES: 
β-cat: 12387"
  },
  {
    "caption": "H Representative reconstructions of control and β-catex3 neurons. Scale bar= 20µm",
    "ncbi_link": "β-cat: 12387"
  },
  {
    "caption": "I Quantification showed decreased dendritic length of β-catex3 neurons [p<0.0001]; no difference was apparent in number of branch points [p=0.3256]. Sholl analysis displayed a less complex dendritic tree of β-catex3 neurons [p<0.0001] (control: n= 20 cells from 5 animals, β-catex3: n= 20 cells from 5 animals).",
    "ncbi_link": "β-cat: 12387"
  },
  {
    "caption": "J The number of basal dendrites was increased in β-catex3 neurons [p=0.0003] (control: n= 20 cells from 5 animals, β-catex3: n= 20 cells from 5 animals).",
    "ncbi_link": "β-cat: 12387"
  },
  {
    "caption": "B Representative reconstructions of control and β-catex3 iDCX neurons at 3dpT. Scale bar= 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "C Analysis of morphology showed increased dendritic length in β-catex3 iDCX neurons at 3dpT [p=0.0320]. The number of branch points was unaltered [p=0.0651]. Sholl analysis indicated increased growth of terminal dendrite branches in neurons of β-catex3 iDCX mice [p<0.0001] (control: n = 25 cells from 9 animals; β-catex3 iDCX: n = 25 cells from 8 animals). D Analysis of morphology showed no difference in dendritic length [p=0.1029] and branch point number [p=0.3726] between experimental groups at 13dpT. Sholl analysis indicated a decrease in length of terminal dendrites in neurons of β-catex3 iDCX mice [p<0.01] (control: n= 23 cells from 9 animals, β-catex3 iDCX: n= 26 cells from 8 animals). ",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "E Spine densities were comparable between experimental groups at 3dpT [iML p=0.1512, oML p=0.3841]. 13dpT β-catex3 iDCX neurons showed significantly increased spine density in the inner molecular layer [iML p<0.0001 , oML p=0.0402] (3dpT: control: n= 20 cells from 3 animals, β-catex3 iDCX: n= 20 cells from 4 animals; 13dpT control: n= 20 cells from 5 animals, β-catex3 iDCX: n= 20 cells from 7 animals). Representative images showing dendritic segments in the inner molecular layer of the DG at 13dpT. Scale bars= 1µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "F Representative images of recombined (GFP+) neurons co-expressing Prox1 (grey) as a marker for neuronal fate and the stage specific markers DCX (red) for immature neurons and Calbindin (red) for mature neurons. Arrows and arrowheads indicate marker negative and marker positive cells, respectively. Scale bar = 10µm. G Fraction of DCX expressing neurons is slightly reduced in β-catex3 iDCX at 3dpT [p=0.0338], while fraction of Calbindin expressing cells is slightly increased in β-catex3 iDCX at 3dpT [p=0.0345]. At 13dpT no difference is visible in stage specific marker expression [DCX p=0.8564, Calbindin p=0.0841] (3dpT: control: n= 12 animals, β-catex3 iDCX: n= 12 animals, 13dpT: control: n= 10 animals, β-catex3 iDCX: n= 14 animals). ",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "B Expression of DCX and Calbindin in BrdU+ neurons was comparable between experimental groups at 3dpT and 13dpT (control: n= 5 animals, β-catex3 iDCX: n= 5 animals).",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "C Representative reconstructions of control and β-catex3 iDCX neurons expressing RFP at 3dpT. Scale bar= 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "D Quantification of dendritic length [p=0.0003], branch points [p=0.0433], and Sholl analysis [p<0.0001] showed a higher dendritic complexity of β-catex3 iDCX neurons at 3dpT (control: n= 22 cells from 4 animals, β-catex3 iDCX: n= 19 cells from 5 animals).",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "E Representative reconstructions of control and β-catex3 iDCX neurons expressing RFP at 13dpT. Scale bar= 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "F Quantification of dendritic length [p<0.0001], and branch points [p=0.0495], and Sholl analysis [p<0.0001] showed a lower dendritic complexity of β-catex3 iDCX neurons at 13dpT (control: n= 20 cells from 4 animals, β-catex3 iDCX: n= 19 cells from 5 animals).",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "B Representative reconstructions of control and β-catex3 iDCX neurons in 24-week old mice at 3dpT. Scale bar = 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "C Dendritic length [p<0.0001] and number of branch points [p<0.0001] was increased in 24-week-old β-catex3 iDCX compared to 24-week-old controls at 3dpT (control: n= 21 cells from 5 animals, β-catex3 iDCX: n= 20 cells from 6 animals). At 13dpT dendritic length [p=0.5788] and number of branch points [p=0.4978] were comparable (control: n= 21 cells from 5 animals, β-catex3 iDCX: n= 20 cells from 8 animals).",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "D Representative images showing dendritic segment of the inner molecular layer of the DG in 24-week old mice at 13dpT. Quantification of the number of spines showed increased spine density in inner molecular and outer molecular layer in 24-week old β-catex3 iDCX mice at 13dpT [iML p=0.0047, oML p<0.0001] (control n=19 cells from 4 animals, β-catex3 iDCX: n= 20 cells from 4 animals). Scale bars = 1µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "E Representative images of recombined (GFP+, green) neurons in 24-week old animals at 13dpT co-expressing Prox1 (grey) as a marker for neuronal fate and the stage specific markers DCX (red) for immature neurons and Calbindin (red) for mature neurons. Arrows and arrowheads indicate marker negative and marker positive cells, respectively. Scale bar= 10µm. F Quantification of marker expression. The fraction of Calbindin expressing cells was increased in the recombined population in β-catex3 iDCX at 3dpT [p=0.0081] and 13dpT [p=0.0259] (3dpT: control: n= 4 animals, β-catex3 iDCX: n= 9 animals, 13dpT: control: n= 8 animals, β-catex3 iDCX: n= 10 animals). ",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "B Representative images of recombined (GFP+, green) BrdU+ (grey) neurons in 24-week old control and β-catex3 iDCX animals at 13dpT expressing the stage specific markers DCX (red) for immature neurons and Calbindin (red) for mature neurons. Arrows and arrowheads indicate marker negative and marker positive cells, respectively. Scale bar= 10µm. C Quantification of DCX and Calbindin expression in BrdU+ recombined cells. At 13dpT, labeled neurons in β-catex3 iDCX animals show a shift towards a more mature marker profile [DCX p=0.0238, Calbindin p=0.0714] (3dpT: control: n= 4 animals, β-catex3 iDCX: n= 8 animals; 13dpT control: n= 5 animals, β-catex3 iDCX: n= 5 animals). ",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "D Representative reconstructions of RFP-birthdated control and β-catex3 iDCX neurons in 24-week old mice at 3dpT. Scale bar= 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "E Quantification of dendritic length [p=0.0007], branch points [p=0.3909], and Sholl analysis [p=0.0001] showed increased complexity of birthdated β-catex3 iDCX cells at 3dpT (control: n= 20 cells from 4 animals, β-catex3 iDCX: n= 19 cells from 5 animals).",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "F Representative reconstructions of RFP-birthdated control and β-catex3 iDCX neurons in 24-week old mice at 13dpT. Scale bar= 20µm.",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "G Quantification of dendritic length [p=0.1857], branch points [p=0.1331], and Sholl analysis [p=0.1501] showed no difference between β-catex3 iDCX and control cells at 13dpT (control: n= 18 cells from 4 animals, β-catex3 iDCX: n= 20 cells from 4 animals)",
    "ncbi_link": "β-cat: 12387
DCX: 13193"
  },
  {
    "caption": "B) Characterization of the Doxycycline-inducible cell lines expressing siRNA resistant wild type (WT) or mutant (TMA or TMD) FLAG/HA-tagged PALB2. The cell lines were transfected with UNC (Negative Control) or PALB2 siRNA for 24 hours prior to induction with Doxycycline. Immunoblots were performed with indicated antibodies.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "A) PALB2 cell lines transfected with PALB2 siRNA followed by inducible expression of siRNA resistant PALB2 versions were exposed to 15 Gy of IR and fixed for IF 2 hours later. Z-stack images were acquired with a 60X oil objective (Deltavision). Z stack max intensity projection, background subtraction, and foci count was done using ImageJ/Fiji. (* p<0.0001, unpaired Student's t-test). Scale bar = 5μm.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "B) PALB2 cell lines were transfected and the exogenous PALB2 induced as in Figure 3A before they were pulsed with 10 μM EdU for 20 minutes prior to addition of 2 mM HU. 24 hours later the cells were fixed and processed for IF as in Figure 3A. Cells in S-phase (EdU+) at the time of HU treatment were Click-IT labeled with an Alexa Fluor 647 azide and RAD51 foci in EdU positive cells were enumerated using ImageJ/Fiji. (* p<0.0001, unpaired Student's t-test). Scale bar=5μm.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "C) HeLa DR-GFP cell line was used to analyze homologous recombination activity. Cells were transfected with PALB2 siRNA followed by transfection of I-SceI together with empty vector (EV), WT-, TMA-, or TMD-PALB2 the next day. 72 hours later cells were fixed and analyzed by FACS. The percentage of cells with GFP signal from the empty vector sample was set to one (dotted line). The graph shows a representative image from three biological repeats (error bars=SEM).",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "D) Phosphorylation of PALB2 supports RAD51 foci. Cells were transfected with siPALB2 overnight followed by forward transfection of siFBH1/siBLM for 6 hours then induced for expression of PALB2 (WT and TMA). 24 hours following induction cells were pulsed with EdU and exposed to HU as in Figure 3B. Cells in S-phase (EdU+) at the time of HU treatment were Click-IT labeled with an Alexa Fluor 647 azide and RAD51 foci in EdU positive cells were enumerated using ImageJ/Fiji (* p<0.0001, unpaired Student's t-test). Representative images of displaying RAD51 (green) and HA-PALB2 (red) localization in HU treated EdU positive (not shown) cells. Scale bar=5μm.",
    "ncbi_link": "BLM: 641
FBH1: 84893
PALB2: 79728"
  },
  {
    "caption": "A) U2OS and PALB2 cell lines were transfected with UNC (Negative Control) or PALB2 siRNA and 24 hours later Doxycycline was added to the PALB2 cell lines. Left panel, cells were treated the following day with IR (5 Gy) and 2 hours later Nocodazole was added for 6 hours, or treated with only Nocodazole for 6 hours. Right panel, cells were treated with IR (5 Gy) and left to recover for 16 hours. Cells were fixed and stained with the pMPM2 antibody to detect the mitotic cells by flow cytometry. The percentages of mitotic cells in the IR+Nocodazole samples were normalized to the Nocodazole samples (left panel, n=3, error bars=SEM). For the samples with the 16 hour recovery after IR the percentage of mitotic cells in the WT-PALB2 expressing cells was set to one (right panel). (n=3, **p<0.005, *p<0.05, unpaired Student's t-test, error bars=SEM).",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "B) The relative intensity of phosphorylated H2AX (pS139) was examined in the total population of WT- and TMA-PALB2 expressing cell lines 18 hours post exposure to IR (5 Gy). Cell lines were prepared as in above, fixed at the indicated time point, and stained for pH2AX. Cells were imaged with a 20X air objective on a Scan^R workstation (Olympus), mean relative pH2AX intensity was calculated from background subtracted images using the Scan^R analysis software. (* p<0.0001, unpaired Student's t-test).",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "C) Number of 53BP1 nuclear in TMA-PALB2 expressing G1 daughter cells. Cell lines were prepared as above and left untreated (NT) or exposed to IR (3 Gy), and 16 hours later Cytochalasin B was added for 8 hours to block cytokinesis. The irradiated bi-nucleated cells were scored for 53BP1 nuclear bodies. Scale bar = 10μm.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "Display of differentially expressed genes in NeuNT tumors (WT, TNCKO) as volcano plot representing all associated genes in WT tumors. N = 3 tumors per genotype. (A) Log2 Fold Change (X-axis) and the negative log10 (P.Value) (Y-axis) is displayed, the blue line indicating p = 0.05 (Y-axis), points above the line, p < 0.05. The dashed red lines indicate the log 2 Fold Change cutoff of -0.25 and 0.25, respectively (X-axis). Green dots represent genes that display both statistical significance (p < 0.05) and fold changes -0.25 and 0.25, respectively. Selected genes regulated by TNC are marked in red (type I interferon response) or pink (Cxcl12) dot.",
    "ncbi_link": "Cxcl12: 20315
type I interferon: 15975
TNC: 21923"
  },
  {
    "caption": "(A) Representative staining images (N = 5) of tissue from TNC  high (WT/shC) and TNC low (KO/shTNC) tumors (N = 5 per condition) with the indicated antibodies. Arrows point at the respective immune subtype. Scale bar, 50 µm.",
    "ncbi_link": "TNC: 21923"
  },
  {
    "caption": "(D, E)  Apoptosis measurement upon tumor staining for  cl. casp3 (D) and signal quantification per field (E) in TNC high and TNC low tumors (N = 7 per condition), 2 sections per tumor, 5 random fields. *** p = 0.0006, Mann-Whitney test, Mean ± SEM. Scale bar, 50 µm.",
    "ncbi_link": "TNC: 21923"
  },
  {
    "caption": "(I, J) Detection (I) and quantification (J) of CD8 TIL in lung metastasis of NeuNT WT and TNCKO mice (N = 3 mice, n = 7 and 12 lung metastases, respectively). Scale bar, 100 µm. ** p = 0.0097, Mann Whitney test. Mean ± SEM.",
    "ncbi_link": "TNC: 21923"
  },
  {
    "caption": "(E) Analysis of Cxcl12  (qRT-PCR) in tumor cells upon pretreatment with the indicated inhibitors for 45 minutes (GW, BOP, DMSO and PBS as control respectively) or 60 minutes (Sunitinib) and 6 hours (Cli95) (6 hours DMSO as control) before incubation with TNC for 24 hours. N = 6 independent experiments, ** p = 0.0022, Mann Whitney test. Mean ± SEM.",
    "ncbi_link": "Cxcl12: 20315
TNC: 21923"
  },
  {
    "caption": "(I-L) qRT-PCR assessment of Neu (I), Cd8a (J), Ifnγ (K) and Gzmb (L) by qRT-PCR. PBS (N = 16) and AMD (N = 19) treated mice, *, p = 0.0364, Mann whitney test (I), **, p = 0.0086 unpaired t-test (J), **, p = 0.0055, unpaired t-test (K), ***, p = 0.0003 unpaired t-test (L), respectively. The central band represents the median, the ends of the box the first and the third quartiles, and the whiskers reach from each quartile to the minimum or maximum.",
    "ncbi_link": "Cd8a: 12525
Neu: 13866
Gzmb: 14939
Ifnγ: 15978"
  },
  {
    "caption": "(D-G)  Kaplan Meier  analysis to address correlation of TNC expression (D), total  numbers of CD8 TIL (E), combined high (above median) CD8 TIL and high or low (above/below median) TNC (F) and stromal CD8  cells (G) with metastasis-free survival (MFS) of breast cancer patients. Stromal CD8- or CD8+ is defined as below or above median  stromal CD8 TIL per area. Log-rank test.",
    "ncbi_link": "TNC: 3371"
  },
  {
    "caption": "(H, I) Correlation of TNC  and CD8a levels with overall survival  (OS) using survival analysis on breast cancer patient cohort GSE 19783-GPL6580. Hazard ratio (HR) and p values are indicated in Appendix Fig. S5N. Log-rank test.",
    "ncbi_link": "CD8a: 925
TNC: 3371"
  },
  {
    "caption": "(D) Kaplan Meier survival analysis of breast cancer patients upon stratification into tumors with a CXCL12 Hscore below or above the median, p = 0.002. Mann-Whitney test. (E) Survival analysis of  breast cancer patients in the GSE 19783-GPL6580 cohort upon stratification into tumors with high or low expression of TNC and CXCL12. Log-rank test. HR and p values are indicated, ",
    "ncbi_link": "CXCL12: 6387
TNC: 3371"
  },
  {
    "caption": "K qPCR analysis of human β2-microglobulin (B2M), human specific mitochondrial (Mito) and mouse specific (β-actin) gene expression levels in UC-MSCs, mouse derived spleen cells or FACS sorted CD45+ mouse cells after 24 hrs co-culture with UC-MSCs (n=3 biological replicates). n/d = not detected.",
    "ncbi_link": "Mito: 
β-actin: 11461
B2M: 567
β2-microglobulin: 567"
  },
  {
    "caption": "(K) Representative immunofluorescence staining  of ∆FosB (green) in cultured MSNs  extracted from mutant mice  lacking ALK4  in GABAergic neurons  (Gad67Cre;Alk4fl/fl) and control mice  (Alk4fl/fl) after exposure to consecutive stimulation (same treatment in both treatment days) with activin A (Act), SKF81297  (SKF) or their combination as indicated. Counterstaining  with MAP2  and DAPI  is shown in the second and fourth rows. Scale bar, 25μM. (L) Quantification of  ∆FosB+ nuclei  in cultured MSNs  from mutant and control mice  after the indicated treatments (same treatment in both treatment days). Results are expressed as average ± SEM of % of MAP2+ cells displaying  ∆FosB in the nucleus. N=6. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "ALK4: 11479
Alk4: 11479
Cre: 2777477
Gad67: 14415"
  },
  {
    "caption": "(I) RT-qPCR analysis of PCBP1  mRNA in cultured MSNs  exposed to consecutive stimulation as indicated (same treatment in both treatment days). Results are expressed as average ± SEM of fold change over vehicle. No significant differences were found by one-way ANOVA followed with Tukey's multiple comparisons test (p≥0.05; N=4). Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "PCBP1: 23983"
  },
  {
    "caption": "(D) Representative images of RNA-PLA  (green) between PCBP1  (left) or Smad3  (right) and sequences in exon 4 (pE4) of FosB  mRNA, respectively, in HeLa  cells exposed to consecutive stimulation (same treatment in both treatment days) as indicated. Counterstaining  with phalloidin and DAPI  is shown in the second and fourth columns. Scale bars, 20μM. (E, F) Quantification of RNA-PLA between PCBP1  (E) or Smad3  (F) and pE4 in HeLa  cells after the indicated treatments. Results are expressed as average ± SEM of number of  RNA-PLA  dots per cell. Only nuclear  dots were quantified in this analysis. N=4. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "FosB: 2354"
  },
  {
    "caption": "(G) Representative images of RNA-PLA  (green) between PCBP1  (left) or Smad3  (right) and sequences in exon 4 (pE4) of FosB  mRNA, respectively, in cultured MSNs  exposed to consecutive stimulation as indicated. Counterstaining  with phalloidin  and DAPI  is shown in the second and fourth columns. Scale bars, 20μM. (H, I) Quantification of RNA-PLA   between PCBP1  (E) or Smad3  (F) and pE4 in cultured MSNs  after the indicated treatments. Results are expressed as average ± SEM of number of RNA-PLA  dots per cell. Only nuclear  dots were quantified in this analysis. N=4. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "FosB: 14282"
  },
  {
    "caption": "(D) Representative immunofluorescence staining  of ∆FosB (red) in cultured MSNs  treated with scrambled and shPCBP1 lentiviruses  and exposed to consecutive stimulation (same treatment in both treatment days) with activin A  (Act), SKF81297  (SKF) or their combination as indicated. Counterstaining  with green fluorescent protein (GFP, expressed by the lentiviruses) and DAPI  is shown in the second and fourth rows. Scale bar, 25μM. (E) Quantification of ∆FosB+ nuclei  in cultured MSNs  treated with scrambled and shPCBP1 lentiviruses  followed by the indicated treatments. Results are expressed as average ± SEM of % of GFP+ cells displaying ∆FosB in the nucleus. N=4. Data information: *, p<0.05; **, p<0.01;***, p<0.001; two-way ANOVA followed with Tukey's multiple comparisons test in E). N denotes biological replicates.",
    "ncbi_link": "PCBP1: 23983"
  },
  {
    "caption": "(A-F) RT-qPCR analysis of FosB  (A, D), c-Fos (B, E) and  ∆FosB  (C, F) mRNAs in NAc  of Gad67Cre;Alk4fl/fl (A-C) mutant mice  1 hour (A-C) or 24 hour (D-F) after the second saline  (Sal) or cocaine  (Coc) injection of TIPS. Results are expressed as average ± SEM of fold increase over the saline  group (Sal/Sal) of  Gad67Cre mice. N=5. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "Alk4: 11479
Cre: 2777477
c-Fos: 14281
∆FosB: 14282
FosB: 14282
Gad67: 14415"
  },
  {
    "caption": "(G) Representative immunofluorescence staining  of ∆FosB in Nac  of control (Gad67Cre) and mutant (Gad67Cre;Alk4fl/fl) mice, 24 hours after the second injection of the TIPS protocol. Scale bars 20 μm. (H) Quantification of ∆FosB positive cells 24 hours after the second injection of TIPS protocol in the Nac  of Gad67Cre and Gad67Cre;Alk4fl/fl mice. Results are expressed as average ± SEM of the number of  ∆FosB+ cells per mm2. At least 10 images from both left and right hemispheres were analyzed per mouse  and condition. N=5. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "Alk4: 11479
Cre: 2777477
Gad67: 14415"
  },
  {
    "caption": "(I)  Western blot  analysis of FosB  and  ∆FosB in in NAc  of Gad67Cre and Gad67Cre;Alk4fl/fl mice 24 hour after the second injection of TIPS. Blots  were probed with an antibody that recognizes both FosB  (upper band, 48kDa) and ∆FosB (lower band, 38 kDa). Lower blot  shows reprobing with anti-β-actin. (J, K) Quantification of FosB  (J) and ∆FosB (K) levels in NAc  of Gad67Cre and Gad67Cre;Alk4fl/fl mice  24 hour after the second injection of TIPS. Results are expressed as average ± SEM of fold increase of FosB  and ∆FosB  over the saline group (Sal/Sal) of  Gad67Cre mice  normalized to  β-actin levels. N=4s. Data information: *, p<0.05; **, p<0.01;***, p<0.001; one-way ANOVA followed with Tukey's multiple comparisons test. N denotes biological replicates.",
    "ncbi_link": "Alk4: 11479
Cre: 2777477
Gad67: 14415"
  },
  {
    "caption": "(A) Fluorescence micrograph images of representative cells stained for NONO and NEAT1_2 after transfection with plasmids expressing YFP fused NONO_WT and NONO_∆RRM1 protein. DAPI (blue) stain indicates cell nuclei, YFP fused NONO (green) and NEAT1_2 RNA FISH (red). (B) The enrichment of mean NONO fluorescence detected within RNA FISH foci is quantitatively determined as a ratio relative to mean nuclear NONO fluorescence in (A). Bars are SD. The numbers of biological replicates are indicated in (A).",
    "ncbi_link": "YFP: 
NEAT1: 283131
NONO: 4841"
  },
  {
    "caption": "Sphericity per NONO segment, NONO foci number per nucleus and NONO foci size between YFP fused NONO_WT and NONO_∆RRM1 plasmids. Bars are SD. Biological replicates n=60 in (C) and n=50 in (D)",
    "ncbi_link": "YFP: 
NONO: 4841"
  },
  {
    "caption": "(A) Relative NONO mRNA and protein levels in KELLY cells treated with control or NONO KD siRNAs. Representative Western blot image for NONO protein.",
    "ncbi_link": "NONO: 4841"
  },
  {
    "caption": "(B) Western blot quantitation analysis of GATA2 and HAND2 protein levels between control and NONO KD siRNAs. (C) Representative Western blot images for GATA2 and HAND2 proteins in (B).",
    "ncbi_link": "NONO: 4841"
  },
  {
    "caption": "Effect of TFL457 on MEF2-promoter activity. Cultures transfected with pMEF2 (two minimal wild type MEF2 elements) or pMEF2mut (mutant) were preincubated with CPPs (25 μM, 30 min) and treated with NMDA (100 µM, 2 h). Means ± SEM of luciferase activities obtained in excitotoxicity, relative to values found in cells treated with same peptide and no NMDA, are presented.",
    "ncbi_link": "luciferase: 
MEF2: 74490"
  },
  {
    "caption": "Effect on CRE-promoter activity. pCRE contains two minimal CREs. Peptide preincubation was as above with or without KG-501 (10 µM). Mean ± SEM luciferase activities are given relative to values in cells treated with the same peptide but no NMDA or KG-501.",
    "ncbi_link": "CRE: 
luciferase: "
  },
  {
    "caption": "Effect on NMDAR-subunit promoters. Cells transfected with pGluN1 or pGluN2A were treated and analyzed as in panel A (pGluN1, *p = 0.016; pGluN2A, *p = 0.029; n = 14).",
    "ncbi_link": "NMDAR: 
GluN1: 24408
GluN2A: 14811"
  },
  {
    "caption": "Effects on BDNF promoter III or TrkB promoter. Cells transfected with pIIIBDNF (n = 9), pTrkB (n = 7) or pCRE (n = 5), as a control, were processed as above but using 20 µM NMDA for 4 h. Data are presented and analyzed as in panel A (pCRE, **p = 0.0098; pIIIBDNF, *p = 0.029; pTrkB, *p = 0.033).",
    "ncbi_link": "BDNF promoter III: 24225
IIIBDNF: 24225
CRE: 2777477
TrkB: 18212"
  },
  {
    "caption": "Effects of TFL457 on mRNA levels of CREB/MEF2-regulated genes. Total RNA was extracted from cultures preincubated with CPPs (25 μM, 30 min) and treated or not with NMDA (100 µM, 4 h). Levels of mRNA were normalized to NSE (genes expressed in neurons, left panel) or GAPDH (neuronal and glial expression, right panel). Means ± SEM of levels obtained in excitotoxicity relative to values found in cells treated with same peptide and no NMDA are presented. Differences found in excitotoxicity were analyzed by ANOVA test followed by post-hoc Tukey HSD test (GluN1, ***p = 0.00096; GluN2A, p = 0.98; TrkB-FL, ***p = 0.00037; BDNF, *p = 0.045; n = 8).",
    "ncbi_link": "GAPDH: 
NSE: 
BDNF: 12064
CREB: 78284///208677///208647///26427///231991///12913///11911///12912
GluN1: 24408
GluN2A: 14811
MEF2: 74490
TrkB: 18212"
  },
  {
    "caption": "(C) Micrographs of starved HEK GFP-LC3 cells treated with nontargeting or siSNX18-3 siRNA. (left and middle) 3 × 3 fields of cells. (right) Close-up of a few cells from the respective population. The images in the right panels are shown again in Fig. S1 B alongside cells treated with other SNX18-targeting siRNAs. Bars, 10 µm. See also Table S1 and Table S2.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(A) HEK GFP-LC3 cells transfected with control (siCtrl) or two different SNX18 siRNA oligos (siSNX18-3 and siSNX18-5) were starved or not starved for 2 h in the presence or absence of BafA1. GFP-LC3 lipidation and SNX18 protein knockdown were monitored by immunoblotting. The graph shows the average GFP-LC3-II relative to actin normalized to siCtrl-1 fed ± SEM (error bars), n = 4.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(B) The degradation of long-lived proteins in HeLa cells transfected with control or SNX18 siRNA was quantified after 4 h of starvation in the absence or presence of 3-MA and normalized to the degradation in fed cells (mean ± SEM [error bars], n = 3).",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(C) HEK GFP-LC3 cells were transfected with control or SNX18 siRNA and then with a myc control or siRNA-resistant myc-SNX18 plasmid. The number of GFP-LC3 spots per cell was quantified (graph shows mean ± SEM [error bars], n = 3).",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(D) HEK GFP-LC3 cells were transfected with myc-SNX18 or a myc control plasmid and treated as in A. The graph shows the average LC3-II levels relative to actin normalized to myc-transfected fed cells, ±SEM (error bars). n = 3.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(E) HEK GFP-LC3 cells were transfected with control or Atg7 siRNA and then with myc-SNX18 or a myc control plasmid, followed by quantification of the number of GFP-LC3 spots per cell (graphs show mean ± SEM [error bars], n = 3). Representative images are shown. Bars, 5 µm.",
    "ncbi_link": "Atg7: 10533
SNX18: 112574"
  },
  {
    "caption": "(F) The degradation of long-lived protein in HeLa cells transfected with myc-SNX18 or a myc control plasmid was quantified as in B (graph shows mean ± SEM [error bars], n = 4). *, P < 0.05; **, P < 0.01. See also Figs. S1 and S2.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(F) HeLa cells were transfected with control or SNX18 siRNA, starved for 2 h, and immunostained against SNX18 and Atg16L1.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(G) HEK GFP-DFCP1 cells were transfected with control or SNX18 siRNA, starved for 50 min, and immunostained for Atg16L1. All images are from confocal microscopy. Inset panels show enlarged views of the boxed regions. Bars, 5 µm. See also Fig. S3.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(D) HeLa cells were transfected with the indicated myc-SNX18 plasmids for 6 h and starved for an additional 2 h before harvest. Equal parts of cytosol (C) and membrane (M) fractions were analyzed by Western blotting. The graph shows the average membrane-bound myc-SNX18 ± SEM (error bars), n = 3.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(E and F) HEK GFP-LC3 cells were transfected with the indicated mCherry-SNX18 (E) or mycSNX18 (F) constructs for 16 h. The number of GFP-LC3 spots per transfected cell (E; graph shows mean ± SEM [error bars], n = 5) or ratio of LC3-II to actin determined by Western blotting (F) was quantified.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(E and F) HEK GFP-LC3 cells were transfected with the indicated mCherry-SNX18 (E) or mycSNX18 (F) constructs for 16 h. The number of GFP-LC3 spots per transfected cell (E; graph shows mean ± SEM [error bars], n = 5) or ratio of LC3-II to actin determined by Western blotting (F) was quantified.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(G and H) HEK GFP-LC3 cells transfected with myc-SNX18 or a myc control plasmid alone (G) or together with CFP-FRB and mRFP-FKBP or mRFP-FKBP 5pase (H) for 6 h were treated or not treated with 5 µM ionomycin (G) or 2.5 µM A/C heterodimerizer (rapalog; H) for the last 3 h before analysis of the total intensity of GFP-LC3 spots per transfected cell (graph shows mean ± SEM [error bars], n = 3).",
    "ncbi_link": "FKBP: 2280
FRB: 2475
SNX18: 112574"
  },
  {
    "caption": "(I) MEFs were transfected with myc, myc-SNX18 WT, or KR for 16 h, starved or not starved for 2 h, and immunostained for endogenous Atg16L1. Insets show enlarged views of the boxed regions. Bars, 5 µm.",
    "ncbi_link": "SNX18: 170625"
  },
  {
    "caption": "(A) HeLa GFP-SNX18 cells were starved for the indicated time, followed by incubation in full medium (Refeed) where indicated. Cell lysates were analyzed for LC3 by immunoblotting, or immunoprecipitated with GFP-Trap before immunoblotting against SNX18(pS233) and GFP. The ratio of pS233 to GFP, and the ratio of LC3-II to LC3-I, was quantified, and normalized to 1 for the zero-time sample in both cases (graph shows mean ± SEM [error bars], n = 4; *, P < 0.05).",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(B) The indicated myc-SNX18 PX-BAR constructs were transfected into HeLa cells, and their tubulation efficiency was measured by scoring the percentage of cells displaying more than three elongated structures longer than 5 µm (n = 300). The graph shows the mean of two independent experiments ± range (error bars). Bars, 10 µm.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(C) The indicated myc-tagged SNX18 constructs were transfected into HEK GFP-LC3 cells, and the number of GFP-LC3 spots per cell was quantified. The graph shows mean ± SEM (error bars), n = 5.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(D) HeLa GFP-LC3 cells were transfected with the indicated myc-tagged SNX18 constructs for 16 h, starved for 2 h, and analyzed by confocal imaging. Bars, 10 µm.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(E) HEK GFP-LC3 cells were transfected with myc-SNX18 WT or myc-SNX18 PX-BAR constructs, and the number of GFP-LC3 spots per cell was quantified. The graph shows mean ± SEM (error bars), n = 3.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(F) HeLa GFP-LC3 cells were transfected with siRNA against Atg16L1 and later with myc-SNX18 constructs before immunostaining and confocal imaging. Bar, 5 µm.",
    "ncbi_link": "Atg16L1: 55054
SNX18: 112574"
  },
  {
    "caption": "(A) GFP, GFP-LC3, or GFP-LC3 G120A were immunoprecipitated from transfected HeLa cells. The immunoprecipitates and 2% of the lysate were analyzed by immunoblotting against SNX18. The GFP proteins were detected by Ponceau staining.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) Peptides with the sequence YGGYQASQGSDDDWDDEWDDSSTVADEPGAL (SNX18 WT) or with the first (SNX18 W154S), the second (SNX18 W158S), or both (SNX18 W154S/W158S) W mutated to S were spotted on membranes that were incubated with GST, GST-LC3B, or GST-GABARAP. Binding was analyzed as in B.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "(E) HeLa GFP-LC3 cells were transfected with myc-SNX18 W154S/W158S mutant, starved for 2 h, immunostained against myc, and analyzed by confocal imaging. Bar, 10 µm. (F) Indicated myc-SNX18 constructs were transfected into HEK GFP-LC3 cells, and the number of GFP-LC3 spots per cell was quantified. The graph shows mean ± SEM (error bars), n = 3. *, P < 0.05.",
    "ncbi_link": "SNX18: 112574"
  },
  {
    "caption": "Recycling endosomes provide membranes for SNX18-mediated GFP-LC3 membrane trafficking and remodeling. (A) HeLa cells were starved or not starved for 2 h before fixation and immunostaining against endogenous SNX18, Rab11, and TfR. (B) Cells were transfected to express flag-Atg16L1, starved, and immunostained against Rab11 or TfR and flag. (C) Cells were starved and immunostained against TfR, Atg16L1, and SNX18. (D) Cells were transfected with control or SNX18 siRNA, starved, and immunostained against SNX18 and Rab11. Inset panels show enlarged views of the boxed regions. (E) Cells were transfected with control or Rab11 a+b siRNA, starved, and immunostained against SNX18 and Atg16L1. Cells were imaged by confocal microscopy. Bars, 5 µm.",
    "ncbi_link": "Rab11: 8766
SNX18: 112574"
  },
  {
    "caption": "(B and C) RNAi against SH3PX1 (GFP-positive clones) decreases formation of LTR punctae in response to 4 h of starvation in 20% sucrose (B) and inhibits formation of mCherry-Atg8a-positive autophagosomes in response to 2 h starvation (C). Genotypes: (B and D) hs-flp; UAS-dicer/+; Act>CD2>GAL4 UAS-GFPnls/UAS-SH3PX1 RNAi; (C and E) hs-flp; UAS-dicer/+; r4:mCherry-Atg8a Act>CD2>GAL4 UAS-GFPnls/UAS-SH3PX1 RNAi;",
    "ncbi_link": "SH3PX1: 39136"
  },
  {
    "caption": "(D and E) RNAi against SH3PX1 inhibits formation of LTR (D) and mCherry-Atg8a-positive structures (E) at early stages of developmental autophagy in fat bodies of 110-h-old larvae. Genotypes: (B and D) hs-flp; UAS-dicer/+; Act>CD2>GAL4 UAS-GFPnls/UAS-SH3PX1 RNAi; (C and E) hs-flp; UAS-dicer/+; r4:mCherry-Atg8a Act>CD2>GAL4 UAS-GFPnls/UAS-SH3PX1 RNAi;",
    "ncbi_link": "SH3PX1: 39136"
  },
  {
    "caption": "(F) There was no change in mCherry-Atg8a in SH3PX1 mutant clones (GFP negative, outlined) in well-fed larvae. Genotypes: (F and G) hs-flp; Cg-GAL4 UAS-mChAtg8a/+; FRT80B UAS-2XeGFP/FRT80B SH3PX1HK62b.",
    "ncbi_link": "SH3PX1: 39136"
  },
  {
    "caption": "(G) Decreased formation of mCherry-Atg8a-positive autophagosomes in SH3PX1 mutant clones (GFP negative, outlined) in fat bodies from larvae starved in 20% sucrose for 3 h. Bars, 20 µm. (H) The graph shows quantification of total mCherry-Atg8a spot intensity per cell for WT and SH3PX1 mutant cells. The graph shows mean ± SEM (error bars); ***, P < 0.001. Genotypes: (F and G) hs-flp; Cg-GAL4 UAS-mChAtg8a/+; FRT80B",
    "ncbi_link": "SH3PX1: 39136"
  },
  {
    "caption": "(D) Inhibition of PI3K by overexpression of a dominant-negative version (the p60 subunit alone) is sufficient to induce formation of large micron-scale Hpo sensor punctae, while activation of Akt by overexpression of a myristylated form of the protein is sufficient to reduce formation of the small apical Hpo sensor punctae that are normally observed in control animals.",
    "ncbi_link": "Akt: 41957
p60: 33203"
  },
  {
    "caption": "(A) Expanded (Ex; endogenously tagged with YFP) localises to the apical domain of columnar follicle cells at stages 9/10 of oogenesis. (B) The Hpo dimerization sensor localises in a similar pattern to Ex.",
    "ncbi_link": "Ex: 33218"
  },
  {
    "caption": "(G) Moderate overexpression of untagged Kib is sufficient to induce formation of large micron-scale HpoKD-Venus condensates that primarily localise apically. DAPI marks nuclei (blue). (H) Overexpression of Kib-GFP with the Gal4/UAS system is sufficient to induce formation of large micron-scale cytoplasmic condensates.",
    "ncbi_link": "Gal4: 855828
Kib: 41783"
  },
  {
    "caption": "(A) Expression of KIB-GFP, KIB∆C-GFP or KIB∆M+C-GFP in human HEK293T cells and co-staining for pLATS. DAPI marks nuclei in blue.",
    "ncbi_link": "GFP: 
KIB: 23286"
  },
  {
    "caption": "A. Differentially expressed proteins in PtenStat3pc-/- vs. Ptenpc-/- proteomic samples. Colors indicate adj.p-value and log2-FC. (Black = Log2-FC ≤ 1 & adj. p-value ≥ 0.05, orange = Log2-FC > 1 & adj. p-value ≥ 0.05, red = Log2-FC > 1 & adj. p-value < 0.05). FC = fold change.",
    "ncbi_link": "Pten: 19211
Stat3: 20848"
  },
  {
    "caption": "B. STAT3 immunohistochemistry- staining of wild type, Ptenpc-/-, PtenStat3pc-/- mouse prostates. Scale bar = 100µm.",
    "ncbi_link": "Pten: 19211
Stat3: 20848"
  },
  {
    "caption": "E. Metabolite concentrations in nmol/µg of 5 metabolites in WT, Ptenpc-/- and PtenStat3pc-/- prostates. Box-plot shows median, 1st and 3rd quartiles, and whiskers extend to ± 1.5 interquartile range. Jitter represents biological replicates. ANOVA tests and Tukey multiple comparisons were applied. Red = PtenStat3pc-/- (n = 3), blue = Ptenpc-/- (n = 5), grey = wild type (WT, n=5), q = adj. p.-value, n.s. = not significant.",
    "ncbi_link": "Pten: 19211
Stat3: 20848"
  },
  {
    "caption": "B. Western blot of STAT3, PDK4 and β-TUBULIN proteins in 22Rv1 cells with or without knockdown of STAT3. Ctrl = scrambled control, shSTAT3 = short hairpin knockdown of STAT3.",
    "ncbi_link": "STAT3: 6774"
  },
  {
    "caption": "C. ChIP assay from IL-6 stimulated or non-stimulated 22Rv1 cells with or without knockdown of STAT3 was immunoprecipitated with a STAT3 specific antibody (blue shades) and IgG antibody as negative control (orange shades) followed by qPCR with a promoter- specific primer pair for the PDK4 gene. Bars represent mean ± SD from 2 technical replicates. Precipitated DNA is presented as % of input. One representative experiment is shown. Result of qPCR using primer pair 2 is shown. Ctrl = scrambled control, shSTAT3 = short hairpin knockdown of STAT3, +IL-6 = IL-6 stimulated.",
    "ncbi_link": "PDK4: 5166
STAT3: 6774"
  },
  {
    "caption": "D. Correlation of STAT3, c-MYC and HIF-1α with PDK1-4, PDC- genes (PDHA1, PDHB, PDHX, DLAT, DLD) and TCA/OXPHOS genes (CS, IDH2, IDH3A, SDHB, SDHC, ATP5A1, NDUFS1) in MSKCC PCa (GSE21032). Dot colors represent Pearson correlation (1 = red, -1 = blue), dot sizes represent adj. p-values ≤ 0.05. Only significant correlations are shown. P-values were adjusted with Benjamini-Hochberg method.",
    "ncbi_link": "ATP5A1: 498
CS: 1431
DLAT: 1737
DLD: 1738
HIF-1α: 3091
IDH2: 3418
IDH3A: 3419
c-MYC: 4609
NDUFS1: 4719
PDHA1: 5160
PDHB: 5162
PDHX: 8050
PDK1: 5163
SDHB: 6390
SDHC: 6391
STAT3: 6774"
  },
  {
    "caption": "Overview of the hippocampus of an AAV-APPsα injected cDKO mouse. HA-tag staining (red) reveals APPsα expression within the CA1, CA3 and DG of the hippocampus. Magnification shows the boxed CA1 region. Scale bars: 500 μm (left), 100 µm (right). DG: Dentate Gyrus, CA: Cornus Ammonis.",
    "ncbi_link": "APPsα: 11820"
  },
  {
    "caption": "Western blot analysis of APP expression in hippocampus of LM control (N=5) and cDKO mice (N=5) injected with AAV-Venus or AAV-APPsα. Age of mice: 5-6 months.",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "LTP was induced at hippocampal CA3-CA1 synapses after 20 min baseline recordings (arrowhead, TBS). cDKO mice expressing Venus (red) exhibited significant lower induction and maintenance of LTP (128.12 ± 3.41%) compared to Venus injected LM controls (white, 156.69 ± 4.75%, ###p<0.001). AAV mediated expression of APPsα (green) restored potentiation after start of baseline recording and resulted in an LTP curve comparable to that of LM controls. The LTP induction rate is shown as percentage % of mean baseline slope. Data points were averaged over 6 time points.",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "The deficit of PPF in Venus injected cDKO mice at the 10 ms (#p<0.05) and 20 ms (#p<0.05) ISI was restored by expression of APPsα. n=number of slices. N=number of animals.",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "The spine density deficit of Venus injected cDKOs mice (11% in basal and 18% in midapical dendrites) is rescued by APPsα to LM control levels. Images are maximum projections of deconvolved z-stacks. Scale bar: 5 µm. Spine density was normalized to LM control levels. n=number of neurons (from 5 animals per condition).",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "Compared to LM controls AAV-Venus injected cDKO mice show a significantly reduced basal (##p<0.01, C) and apical (##p<0.01, E) dendritic length and reduced branching in basal (##p<0.01, D) and apical (##p<0.01, F) dendrites. AAV-APPsα injection did neither affect basal (nsp>0.05, C) nor apical (nsp>0.05, E) total dendritic length. However, the total number of basal nodes differed significantly compared to AAV-Venus injected cDKO mice (*p<0.05, D).",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "Sholl analysis of basal dendritic length reveals a significant group effect (repeated measures ANOVA: genotype F(2, 29)=5.038, p<0.05) and a significant distance effect (repeated measures ANOVA: genotype F(5, 145)=250.2, p<0.0001). Due to a significant interaction effect (repeated measures ANOVA: genotype F(10, 145)=4.466, p<0.0001), a post-hoc Sidak's multiple comparison test was performed to further evaluate effects between groups at distinct distances from soma. Compared to Venus injection, AAV-APPsα injection of cDKO significantly increased basal dendritic length at 60 µm (*p<0.05). H Sholl analysis of apical dendritic length reveals an overall significant group effect (repeated measures ANOVA: genotype F(2, 37)=4.776, p<0.05) and a significant distance effect (repeated measures ANOVA: genotype F(18, 666)=47.54, p<0.0001). Due to a significant interaction effect (repeated measures ANOVA: genotype F(36, 666)=1.640, p<0.05), a post-hoc Sidak's multiple comparison test was performed to further evaluate effects between groups at distinct distances from soma. AAV-APPsα expression increased midapical dendritic length at 300 µm (**p<0.01) and 330 µm (**p<0.01) distance from soma compared to AAV-Venus injected cDKO mice.",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "During acquisition learning and after platform reversal to the opposite quadrant, AAV-Venus injected cDKOs (red circles) show considerably longer escape latency compared to AAV-Venus injected LM controls (white circles). AAV-APPsα injected cDKO mice (green circles) show an overall intermediate performance (genotype F(2, 46)=6.361, p=0.0036) and that differs significantly at day 5 of reversal learning compared to AAV-Venus injected cDKO mice (genotype x day F(8,184)=5.266, p<0.0001; **p<0.01).",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "Measurements of swim path length confirms the training performance deficit of cDKO mice compared to LM controls. During the reversal phase, the performance of AAV-APPsα injected cDKOs is significantly improved at day 5 (genotype F(2,46)=16.70, p<0.0001, genotype x day F(8,184)=5.788, p<0.0001; *p<0.05, p<0.01).",
    "ncbi_link": "APPsα: 11820"
  },
  {
    "caption": "In the probe trial, AAV-Venus injected cDKOs (red) spend significantly less time in the target zone compared to AAV-Venus (###p<0.001) injected LM control animals (white) and failed to prefer it significantly over control zones in adjacent quadrants. Note that expression of APPsα (green) largely rescues the deficits of cDKOs. N=22 (LM controls: AAV-Venus), N=18 (cDKOs: AAV-Venus), N=18 (cDKOs: AAV-APPsα). Data represent mean ± SEM. Dashed lines: chance level. Data were analyzed using a mixed ANOVA model with conditions (LM control: AAV-Venus, cDKO: AAV-Venus and cDKO: AAV-APPsα) as between subject factor. Within subject factors were added to explore the dependence of genotype effects on day and place. Significant interactions and main effects were further explored by pairwise FDR-corrected two-tailed Student's t-tests. # indicates significant differences between LM control and cDKO injected with AVV-Venus, * between cDKO injected with AAV-Venus or APPsα, ● between LM control injected with Venus and cDKO injected with AAV-APPsα nsp>0.05, */#/●p<0.05, **/##/●●p<0.01, ***/###/●●●p<0.001.",
    "ncbi_link": "Venus: 
APPsα: 11820"
  },
  {
    "caption": "Overview of the hippocampus of a AAV-APPsβ (HA-tag, red) injected cDKO mouse. APPsβ is expressed in CA1, CA3 and DG. Scale bar: 500 μm. DG: dentate gyrus, CA: Cornus Ammonis.",
    "ncbi_link": "HA: 
APPsβ: 11820"
  },
  {
    "caption": "Western blot analysis of HA-APPsα and HA-APPsβ in hippocampi of injected mice (boxed upper panel), probed with an HA-tag specific antibody (lower band, arrowhead; *unspecific signal). Homogenates of AAV injected hippocampi were subjected to ultracentrifigation to detect soluble APPsα and APPsβ (UC supernatant; boxed lower panel). The APP C-terminal antibody Y188 was used to confirm the separation of soluble APPsα from membrane bound full-length APP that is detected in total lysates of AAV-Venus injected littermate controls. Hippocampi of APP-/- mice served as a negative control for antibody specificity.",
    "ncbi_link": "HA: 
Venus: 
APP: 11820
APPsα: 11820
APPsβ: 11820"
  },
  {
    "caption": "Quantification of HA-APPsα and HA-APPsβ expression in total hippocampal homogenates and of soluble HA-APPs after UC normalized to β-tubulin. Note the comparable expression in AAV-APPsα and AAV-APPsβ injected mice. Age: 5-6 months. N=Number of animals. Data represent mean ± SEM. Data were analyzed by unpaired two-tailed Student's t test. nsp>0.05.",
    "ncbi_link": "APPsα: 11820
APPsβ: 11820"
  },
  {
    "caption": "Activity dependent synaptic plasticity was investigated in cDKO after injection of AAV-Venus (red) or APPsβ (blue). F, G AAV-mediated overexpression of APPsß (n=23 slices, blue symbols) failed to rescue the LTP defect of cDKO mice (n=24 slices, red symbols). G TBS induced strengthening of fEPSPs resulted in similar potentiation levels for the last 5 minutes of recording (t75-80). The LTP induction rate is shown as percentage % of mean baseline slope. Data points were averaged over 6 time points. H PPF paradigm yielded no significant differences between viral vector injected cDKO mice. Age: 5-6 months. n=number of recorded slices. N=number of animals. Data represent mean ± SEM. Data were analyzed unpaired two-tailed Students t-test.",
    "ncbi_link": "Venus: 
APPsß: 11820
APPsβ: 11820"
  },
  {
    "caption": "Representative images of Golgi stained midapical and basal dendritic segments of LM control and cDKO animals injected with AAV-Venus or AAV-APPsβ.",
    "ncbi_link": "Venus: 
APPsβ: 11820"
  },
  {
    "caption": "The significant spine density deficit of AAV-Venus injected cDKO mice (red bar) in basal (J) and apical dendrites (K) was comparable and not significantly different (nsp>0.05) from that of AAV-APPsβ injected cDKO mice (blue bar). White bar: AVV-Venus injected LM controls. Images are maximum projections of z-stacks. Scale bar: 5 µm. Spine density is normalized to LM control levels. Age: 5-6 months; n=number of neurons (from 5 animals per condition). Data represent mean ± SEM. Data were analyzed by one-way ANOVA followed by Bonferroni´s post-hoc test. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 .",
    "ncbi_link": "Venus: 
APPsβ: 11820"
  },
  {
    "caption": "Nicotine- and acetylcholine-induced whole-cell current traces of α7-nAChRs expressed in Xenopus oocytes recorded in the absence or presence of CTα16 or CTα16scr, respectively. Note specific robust potentiation of nicotine- and acetylcholine-induced currents by CTα16, but no direct activation of α7-nAChRs by either peptide in the absence of agonist (not shown). Bars indicate application of EC50 agonist concentrations and of the peptide indicated (green: CTα16: grey: CTα16scr). Quantification of potentiation shows that CTα16 enhances nicotine- and acetylcholine-induced currents to a similar extend whereas CTα16scr had no effect.",
    "ncbi_link": "α7-nAChRs: 25302"
  },
  {
    "caption": "B. Control or GOLPH3-KD HeLa cells expressing luminal SI-GFP or the chimeras of sucrose-isomaltase containing the N-terminal cytosolic tails of LCS, Gb3S, GM3S and GD3S were fixed and labelled for surface localized GFP (red). Scale bar, 20 μm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "F. GOLPH3-KD or OE HeLa cells were processed for ShTxB (upper panels) or ChTxB (lower panels) staining followed by flow cytometry analysis. Flow cytometry distributions and the relative scatter plots reporting the percentage of positive cells are shown for each condition.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "A. HeLa cells mock-treated or GOLPH3-KD were transiently transfected with LCS_GFP_RUSH (for simplicity, referred in the text as LCS-GR) and subjected to the synchronisation protocol described in Materials and Methods. Cells were then subjected to IF at each indicated time point: LCS-GR (green), cis Golgi marker GM130 (red), and TGN marker TGN46 (blue). Representative individual Golgi mini-stacks are shown. Scale bar, 1 µm. LCS-GR intra-Golgi trafficking in mock or GOLPH3-KD conditions it has been quantified (right graph) by computational coalescence of line scans, and was performed by normalized line scan analysis (normalisation of the distances was performed considering the GM130 peak as 0, and the TGN46 peak as 1). The n indicated in the graph refers to the number of Golgi stacks analysed in each condition.",
    "ncbi_link": "GFP: 
LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "B. Mock and GOLPH3-KD HeLa cells co-expressing LCS-GR and VSV-G were subjected to the co-synchronisation protocol described in Materials and Methods. Cells were then subjected to IF: LCS-GR or VSV-G (green), GM130 (blue), and TGN46 (red). Representative individual Golgi mini-stacks are shown. Scale bar, 1 µm. C. Quantification of the experiment in (B) was performed by normalized line scan analysis (normalisation of the distances was performed considering the GM130 peak as 0, and the TGN46 peak as 1); n indicated in the graph refers to the number of Golgi stacks analysed in each condition, individual data points and means ± SEM are shown, ***p < 0.001 (Student's t test); ns, not significant. D ",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "D. HeLa cells were transfected with LCS-GR, subjected to the synchronisation protocol (see Materials and Methods), fixed and processed for cryoimmunolabeling with an anti-GFP antibody (15 nm gold particles) and anti-GM130 antibody (10 nm gold particles, black arrowheads) peri-Golgi vesicles containing LCS-GR are marked by red arrowheads. Scale bar, 150 nm.",
    "ncbi_link": "LCS: 9334"
  },
  {
    "caption": "G. HeLa cells expressing LCS-GR mock or GOLPH3-KD were treated and stained as in D. Black arrowheads indicate GM130; peri-Golgi vesicles containing LCS-GR are marked by red arrowheads. LCS-GR in the TGN is marked by blue arrowheads. Scale bar, 150 nm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "H. Quantification of LCS-GR distribution (linear density, LD) across the stack and in peri-Golgi vesicles (data are means ± SEM, number of Golgi stacks is n=17 at 20 min for the CTRL, n=13 at 20 min for the GOLPH3 KD; *p <0.05, **p < 0.01; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "A. PHFs GOLPH3 OE (left), or KD (right), were fixed and processed for IF: Endogenous LCS (green), GOLPH3 (red), TGN46 or DAPI (blue). Dashed lines indicate cells overexpressing or interfered for GOLPH3. Scale bar, 20 µm. Quantification of the amount of endogenous LCS (right graph) at the Golgi; data are means ± SEM derived from two biological replicates, n=42 in CTRL, n=49 in GOLPH3 KD and n=27 in GOLPH3 OE; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "B. GOLPH3-OE HeLa cells were fixed and processed for IF: Endogenous LCS (green), GOLPH3 (red), and TGN46 (blue). Dashed lines indicate cells overexpressing GOLPH3. Scale bar, 20 µm. Quantification of the amount of endogenous LCS (right graph) at the Golgi (data are means ± SEM derived from two biological replicates, n=21 in CTRL, n=11 in GOLPH3 OE; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "C. GOLPH3 OE or KD HeLa cells expressing LCS-HA were fixed and processed for IF: HA (green). Asterisks indicate GOLPH3 OE cells. Scale bar, 20 µm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "D. Assessment of LCS-GR synchronized transport in GOLPH3 OE or KD HeLa cells. Micrographs show cells at the indicated trafficking time points. Scale bar, 20 µm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "G. GOLPH3 OE or KD HeLa cells expressing LCS-HA were treated with bafilomycin A1 (BafA1, 10 nM) for 16 hr, fixed, and processed for IF labelling: LCS (green), LAMP1 (red), and DAPI (blue). Arrowheads indicate LCS and LAMP1 co-localisation. Scale bar, 20 µm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "I. GOLPH3 OE or KD HeLa cells expressing the indicated HA-tagged glycoenzymes were fixed and processed for IF. Asterisks indicate GOLPH3 OE cells. Scale bar, 20 µm.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "J. Number of glycoenzymes-HA positive spots per cell in GOLPH3-KD cells (left panel) and percentage of cells with glycoenzymes-HA in the ER in GOLPH3-OE cells (right panel) are plotted (n is indicated in the graph; data are means ± SEM; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "A. Effects of GOLPH3 KD or OE on glycosphingolipid synthetic flux as assessed by [3H]-sphingosine pulse (2 hr) and chase (indicated times), lipid extraction and HPTLC separation and radioactive counting (data are means ± SD of at least 3 independent experiments; *p <0.05, **p <0.01, ***p <0.001 [Student's t-test]).",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "B. Effects of GOLPH3 KD or OE on sphingolipid levels as assessed by LC/MS of HeLa cells (top) and PHFs (middle). Effects of LCS KD or OE on sphingolipid levels as assessed by LC/MS of HeLa cells (bottom) (data are means ± SD of at least 3 independent experiments; *p <0.05, **p <0.01, ***p <0.001 [Student's t-test]). Targeted lipidomics data from this study are available at Metabolomics Workbench database with the following IDs: ST001673 for HeLa cells, and ST001672 for PHFs.",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "C. Effects of GOLPH3 KD or OE on Gb3 as assessed by MALDI-MS after lipid extraction. Profiles are representative of 3 independent experiments. Untargeted lipidomics data from this study are available at Metabolomics Workbench database with the following ID: ST001674.",
    "ncbi_link": "GOLPH3: 64083"
  },
  {
    "caption": "E. Effects of GOLPH3 KD or OE on ceramide levels as assessed by LC/MS of HeLa cells (top) and PHFs (middle). Effects of LCS KD or OE on ceramide levels as assessed by LC/MS of HeLa cells (bottom). The dotted black box highlights the effects on C16:0 Cer (data are means ± SD of at least 3 independent experiments; *p <0.05, **p <0.01, ***p <0.001 [Student's t-test]). Targeted lipidomics data from this study are available at Metabolomics Workbench database with the following IDs: ST001673 for HeLa cells, and ST001672 for PHFs.",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "A. Cell lysates from HeLa cells KD or OE for either GOLPH3 or LCS were processed for SDS-PAGE and Western blotting with antibodies aimed at evaluating the activation status of the mTOR pathway. Data are representative of at least 3 independent experiments.",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "B. Clonogenic assay of HeLa cells in adherence. 250 HeLa cells KD for either GOLPH3 or LCS were allowed to form colonies for 10 days. Afterward, colonies were fixed and stained as detailed in Materials and Methods. The graph on right reports the number of colonies per well in each indicated condition (data are means ± SEM of 3 independent experiments; *p <0.05, **p <0.01 [Student's t-test]).",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "C. Soft agar colony formation assay of HeLa cells transfected with different concentration of either GOLPH3 (left upper graph) or LCS (left bottom graph) encoding plasmids. Soft agar colony formation assay of HeLa cells KD for either GOLPH3 or LCS (right upper graph). Soft agar colony formation assay of HeLa cells KD for LCS and GOLPH3 OE alone or in combination with LCS KD (right bottom graph). Colonies were stained and quantified as described in Materials and Methods; (individual data points are shown in the graphs; data are means ± SD of at least 3 independent experiments; *p <0.05, ***p <0.001, n.s. = not significant [Student's t-test]).",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "D. Protein lysates from parental (left), GCS-KO (middle), and LCS-KO (right) HeLa cells, CTRL or GOLPH3-OE were processed for SDS-PAGE and WB with the indicated antibodies. Data are representative of at least 3 independent experiments.",
    "ncbi_link": "LCS: 9334
GCS: 2729
GOLPH3: 64083"
  },
  {
    "caption": "E. Soft agar colony formation assay of parental and LCS-KO HeLa cells expressing LCS-HA or GOLPH3. Colony number was quantified; (individual data points are shown in the graphs; data are means ± SD of at least 3 independent experiments; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "HA: 
LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "F. Quantification of soft agar colony formation assay of LNCaP and DU145 prostatic cancer cell lines treated with increasing concentrations of siRNA targeting GOLPH3 or LCS (data are means ± SEM of at least 3 independent experiments; ***p <0.001 [Student's t-test]).",
    "ncbi_link": "LCS: 9334
GOLPH3: 64083"
  },
  {
    "caption": "A. Number of peptides detected of each Elongator subunit purified through Elp4-FLAG pulldown from yeast lacking ELP1, ELP2, or ELP3 as a fraction of the number of Elp4 peptides. Individual data points are represented as circles, while the averages are represented as bars.",
    "ncbi_link": "ELP2: 853114
ELP3: 856019
ELP1: 851100"
  },
  {
    "caption": "B. Plasmids containing ELP2 and the four loop mutants were transformed into elp2Δ yeast. The strains were then plated onto -Ura media containing caffeine. The pRS416 vector is used for these experiments.",
    "ncbi_link": "elp2: 853114"
  },
  {
    "caption": "D. Lysates of Elp4-FLAG-containing yeast expressing the Elp2 loop mutants were incubated with α-FLAG resin and eluted with 3xFLAG peptides then analyzed by Western Blot using α-HA and α-FLAG antibody",
    "ncbi_link": "Elp2: 853114"
  },
  {
    "caption": "(D-E)  Western blot analysis of RIPA soluble-fraction and RIPA-insoluble, urea-soluble fraction of proteins prepared from HEK293T  cells expressing empty plasmid (control), FLAG-KIF5A  WT, FLAG-ΔExon27. Insoluble/soluble KIF5A  fractions were detected with anti-FLAG  and actin  was used as a loading control, three biological replicates. Statistical analysis was performed using student t-test (*p < 0.05, **p<0.01, ***p<0.001). Data represent the mean ± s.d.",
    "ncbi_link": "FLAG: 
KIF5A: 3798"
  },
  {
    "caption": "(A) Sanger sequencing chromatograms  of cDNA from control and patient-derived iMNs  (P1-P3) showing the effect of mutations   on KIF5A  transcripts. While the c.3020+2T>C mutation causes exon 27 skipping, the c.2993-1G>A mutation results in an aberrant transcript with a splice acceptor shifted only by a single nucleotide, leading to a frameshift but containing exon 27. The respective protein product predicted for both mutations  comprise the same C-terminal aberrant 39 amino acid end.",
    "ncbi_link": "KIF5A: 3798"
  },
  {
    "caption": "(E) The production of LasB (a protease of P. aeruginosa) was examined in duodenum (n = 6). Data information: Data were representative and were the mean ± SD from three independent experiments. P values were calculated by unpaired two-tailed t-test for comparison of two groups",
    "ncbi_link": "LasB: 880368"
  },
  {
    "caption": " HEK293 cells were infected with lentiviruses containing negative control shRNA (shNC) or NF45/NF90 specific shRNA (shNF45#1, shNF45#2, shNF90#1 and shNF90#2) for 24 h, and then transfected with rDNA-Luc. Luciferase activity was measured after a further 24 h (n = 3). Western blots show the protein levels of NF45 and NF90.   Empty vector (EV), FLAG-NF45 plasmid (NF45) or FLAG-NF90 plasmid (NF90) were transfected into HEK293 cells for 24 h, and then rDNA-Luc was co-transfected into the cells. Luciferase activity was measured after a further 24 h (n=3). Western blots show the protein levels of FLAG-NF45 and FLAG-NF90.   ",
    "ncbi_link": "FLAG: 
Luc: 
NF45: 3608
NF90: 3609"
  },
  {
    "caption": " The relative luciferase activity of HEK293T cells transfected with empty vector (EV) or FLAG-NF90 (NF90) in combination with rDNA -Luc wild type (WT) or mutated rDNA-Luc reporter plasmid (Mutant) for 24 h. (n=3) Western blot shows FLAG-NF90 protein level.",
    "ncbi_link": "FLAG: 
Luc: 
NF90: 3609"
  },
  {
    "caption": " Co-IP analysis of nucleolar proteins with NF90 in HEK293 cells transfected with EV, and the following plasmids: GFP-S5, GFP-L9, GFP-B23, GFP-UBF, GFP-C23. * represents the target protein. ",
    "ncbi_link": "GFP: 
S5: 64969
C23: 4691
B23: 4869
L9: 6133
UBF: 7343"
  },
  {
    "caption": " HEK293 cells were infected by lentivirus containing NF45-specfic shRNA or NF90-specfic shRNA, and then stimulated in serum for 0, 3 and 6 h. Cell lysates were prepared to analyze the expression levels of the indicated proteins by western blot. ",
    "ncbi_link": "NF45: 3608
NF90: 3609"
  },
  {
    "caption": " CD3+ T cells were first silenced with shNC, shNF45 or shNF90, and then treated with P/I to extract total RNA for qPCR analysis of pre-rRNA. (n=3) ",
    "ncbi_link": "NF45: 3608
NF90: 3609"
  },
  {
    "caption": " The analysis of rDNA-luc activity in Jurkat cells with or without NF90 silence upon P/I stimulation or not. (n=3) ",
    "ncbi_link": "luc: 
NF90: 3609"
  },
  {
    "caption": " Jurkat cells co-transfected with rDNA-luc (wild type or mutant plasmid) with NF90 and/or NFATc2 for 24 h, then rDNA-luc activity was detected after P/I sitmulation or not (DMSO). (n=3) ",
    "ncbi_link": "luc: 
NF90: 3609
NFATc2: 4773"
  },
  {
    "caption": " ChIP analysis of NFATc2 binding to the H42.9 loci in NF90-slienced CD3+ T cells stimulated with P/I for 6 h. (n=3) ",
    "ncbi_link": "NF90: 3609"
  },
  {
    "caption": " CD69 expression, an early marker of lymphocyte activation, in CD3+ T cells infected with shNC, shNF45 or shNF90 lentivirus upon stimulation with P/I for 12 h. ",
    "ncbi_link": "NF45: 3608
NF90: 3609"
  },
  {
    "caption": " B-C PBMC cells with shNC, shNF45 or shNF90 lentivirus infection were stimulated with P/I for 12h, then the freshly replaced medium without P/I after another 24 h culture was harvested for IL-2 and IFN-γ detections by ELISA.(n=3) ",
    "ncbi_link": "NF45: 3608
NF90: 3609"
  },
  {
    "caption": " The proliferation of shNC, shNF45 or shNF90-infected PBMCs was monitored using a CCK-8 assay. (n = 3) ",
    "ncbi_link": "NF45: 3608
NF90: 3609"
  },
  {
    "caption": "ChIP-seq tracks of T (in red; input is in blue) around the Oct4 (7.5 kb). DE, distal enhancer; PE, proximal enhancer. The T-binding peak around the Oct4-DE is indicated (arrowhead). Right: ChIP-qPCR for the enrichment of T on the DE and the regions indicated in Fig EV3E. NC, negative control (the locus without T binding). The enrichment is indicated by the percent input with SDs (three independent experiments with two technical replicates).",
    "ncbi_link": "Oct4: 18999"
  },
  {
    "caption": "Left: A representative confocal image of a mouse embryo at E7.0 bearing T-GFP and Blimp1-RFP transgenic reporters. Scale bar: 50um. Arrowheads indicate Blimp1-positive nascent germ cells in the posterior proximal epiblast. Right: FACS analysis of dissociated mouse embryos without visceral endoderm.",
    "ncbi_link": "GFP: 
RFP: 
Blimp1: 12142"
  },
  {
    "caption": "Expression of the indicated genes measured by qPCR in FACS-sorted cells (E) derived from embryos at different developmental stages (E7.0-7.5). Ten FACS-sorted cells in different cell fractions (E) were used for each individual qPCR analysis with two technical replicates. The ∆Ct values from the average Ct values of Arbp and Ppia are shown (n≥3, log2 scale). P values were calculated by two-tailed unpaired t-test.",
    "ncbi_link": "Arbp: 
Ppia: 606536"
  },
  {
    "caption": "ChIP-seq tracks of T (in red; input is in blue) and core pluripotency factors (in green) around the Blimp1 (100 kb) and Prdm14 (100 kb). The co-bound locus (L#1-4) and the locus exclusively bound by core pluripotency factors but not T (L#5) are indicated by arrow. NC, negative control (the locus without T binding).",
    "ncbi_link": "Blimp1: 12142
Prdm14: 383491"
  },
  {
    "caption": "Expression of Blimp1 and Prdm14 measured by qPCR in PGCLCs derived from indicated ESC lines. The ∆Ct values from the average Ct values of Arbp and Ppia are shown (log2 scale, the mean value of two independent experiments with two technical replicates).",
    "ncbi_link": "Arbp: 
Ppia: 606536
Blimp1: 12142
Prdm14: 383491"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, WDR63 shRNA#2, PCDH control, or PCDH-Flag-WDR63 were subjected to wound-healing (A) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar in (A): 200 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, WDR63 shRNA#2, PCDH control, or PCDH-Flag-WDR63 were subjected to transwell migration (B) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar in (B): 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "(C) Effect of WDR63 knockdown on the migration of A549 cells was analyzed by single cell tracking with time-lapse microscopy at 10 min intervals for 4 h. Scale bar: 200 μm. Cell migration speed, persistence, and mean squared displacement (MSD) were also analyzed using an Excel macro described by Gorelik and Gautreau. Data shown are mean ± SD. n = 3 independent experiments. *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA.",
    "ncbi_link": "WDR63: 126820"
  },
  {
    "caption": "(D) A549 cells expressing control shRNA, WDR63 shRNA#1, WDR63 shRNA#2, PCDH control, or PCDH-Flag-WDR63 were subjected to transwell invasion assay. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar: 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, or WDR63 shRNA#1 plus shRNA-resistant Flag-WDR63 were subjected to transwell migration (E) assays. The shown images are representative of three independent experiments. Cell migration speed, persistence, and mean squared displacement (MSD) were also analyzed using an Excel macro described by Gorelik and Gautreau. Data shown are mean ± SD. n = 3 independent experiments. *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar : 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, or WDR63 shRNA#1 plus shRNA-resistant Flag-WDR63 were subjected to single cell tracking (F) assays. The shown images are representative of three independent experiments. Cell migration speed, persistence, and mean squared displacement (MSD) were also analyzed using an Excel macro described by Gorelik and Gautreau. Data shown are mean ± SD. n = 3 independent experiments. *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar 200 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, or WDR63 shRNA#1 plus shRNA-resistant Flag-WDR63 were subjected to transwell invasion (G) assays. The shown images are representative of three independent experiments. Cell migration speed, persistence, and mean squared displacement (MSD) were also analyzed using an Excel macro described by Gorelik and Gautreau. Data shown are mean ± SD. n = 3 independent experiments. *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar : 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "(H) A549 cells expressing control shRNA, WDR63 shRNA#1, or WDR63 shRNA#2 (each also expressing luciferase) were injected via tail vein into nude mice (n=6 for each group). Three weeks after injection, tumor formation was monitored by bioluminescence imaging. Data shown are mean ± SD; *, P ˂ 0.05; One-way ANOVA.",
    "ncbi_link": "luciferase: 
WDR63: 126820"
  },
  {
    "caption": "(A) WDR63 mRNA and protein levels in A549, H292, and HCT116 cells transduced with empty vector (PCDH) or PCDH-p53. Data shown are mean ± SD; n = 3 independent experiments. **, P ˂ 0.01; ***, P ˂ 0.001; two-tailed Student's t-test.",
    "ncbi_link": "p53: 7157
WDR63: 126820"
  },
  {
    "caption": "(B) WDR63 mRNA and protein levels in A549, H292, and HCT116 cells transduced with control (shctrl) or p53 (shp53) shRNA. Data shown are mean ± SD; n = 3 independent experiments. ***, P ˂ 0.001; two-tailed Student's t-test.",
    "ncbi_link": "p53: 7157
WDR63: 126820"
  },
  {
    "caption": "(C) A549 cells expressing control or p53 shRNA were treated with doxorubicin (Dox, 1μg/ml) for the indicated periods of time. WDR63 mRNA and protein levels were then examined. Data shown are mean ± SD; n = 3 independent experiments. ***, P ˂ 0.001; two-tailed Student's t-test.",
    "ncbi_link": "p53: 7157
WDR63: 126820"
  },
  {
    "caption": "(D) WDR63 mRNA levels in H1299 cells transfected with empty vector (-), wild-type p53, or the indicated p53 mutants. Data shown are mean ± SD; n = 3 independent experiments. ***, P ˂ 0.001; two-tailed Student's t-test.",
    "ncbi_link": "p53: 7157
WDR63: 126820"
  },
  {
    "caption": "(G) A549 cells were transfected with empty vector (ctrl) or Flag-p53 plus the indicated reporter constructs. Twenty-four hours later, reporter activity was measured. Data shown are mean ± SD; n = 3 independent experiments. **, P ˂ 0.01; ***, P ˂ 0.001; two-tailed Student's t-test.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "(H) A549 cells expressing control or p53 shRNA were transfected with pGL3-BS1 and Renilla luciferase plasmids. Twenty-four hours later, cells were treated with or without Nutlin (10 μM) for another 12 h. Reporter activity was then measured. Data shown are mean ± SD; n = 3 independent experiments. **, P ˂ 0.01; two-tailed Student's t-test.",
    "ncbi_link": "luciferase: 
p53: 7157"
  },
  {
    "caption": "(B) Lysates from HEK293T cells expressing HA-Arp2 alone or together with Flag-WDR63 were immunoprecipitated by anti-Flag antibody, followed by western blot analysis. Data shown represent three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "(C) Lysates from HEK293T cells expressing GFP-WDR63 alone or together with Flag-Arp2 were immunoprecipitated by anti-Flag antibody, followed by western blot analysis. Data shown represent three independent experiments.",
    "ncbi_link": "Flag: 
GFP: 
Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "(G) Lysates from HEK293T cells expressing GFP-WDR63 alone or together with the indicated Flag-tagged each single subunit of the Arp2/3 complex were immunoprecipitated with anti-Flag antibody, followed by western blot analysis. Data shown represent three independent experiments.",
    "ncbi_link": "Flag: 
GFP: 
Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "(A) Immunolocalization of Arp2 in a wound-healing assay. A549 cells expressing control or WDR63 were serum-starved for 6 h before they were scratched. Cells were then treated with or without 10% FBS for 30 min, followed by immunofluorescence assay. The branched actin networks were shown by immunostaining with anti-Cortactin antibody. Data shown represent three independent experiments. Scale bar: 20 μm. The lamellipodia formation was quantified by measuring the length of the outer margin of lamellipodia in individual cell (n=20 for each condition), and expressed as the proportion of the total length of the cell perimeter. Data shown are mean ± SD; n = 3 independent experiments. ***, P ˂ 0.001; One-way ANOVA.",
    "ncbi_link": "WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, Arp2 shRNA, or both WDR63 and Arp2 shRNA were subjected to wound-healing (A) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; N.S., no significance; One-way ANOVA. Scale bar in (A): 200 μm.",
    "ncbi_link": "Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, Arp2 shRNA, or both WDR63 and Arp2 shRNA Lysates from these cells were also analyzed by western blot (B). Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; N.S., no significance",
    "ncbi_link": "Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, Arp2 shRNA, or both WDR63 and Arp2 shRNA were subjected to transwell migration (C) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; N.S., no significance; One-way ANOVA. Scale bars in (C : 100 μm.",
    "ncbi_link": "Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, WDR63 shRNA#1, Arp2 shRNA, or both WDR63 and Arp2 shRNA were subjected to transwell invasion (D) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; N.S., no significance; One-way ANOVA. Scale bars 100 μm.",
    "ncbi_link": "Arp2: 10097
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing either control shRNA or WDR63 shRNA#1 were infected with lentiviruses expressing Flag-tagged full-length or truncated WDR63 proteins as indicated. Cells were then subjected to transwell migration (E) The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar: 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing either control shRNA or WDR63 shRNA#1 were infected with lentiviruses expressing Flag-tagged full-length or truncated WDR63 proteins as indicated. Lysates from these cells were also analyzed by western blot (F). Data shown are mean ± SD (n=3). *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing either control shRNA or WDR63 shRNA#1 were infected with lentiviruses expressing Flag-tagged full-length or truncated WDR63 proteins as indicated. Cells were then subjected to transwell invasion (G) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar: 100 μm.",
    "ncbi_link": "Flag: 
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, p53 shRNA, or p53 shRNA plus Flag-WDR63 were subjected to wound-healing (A) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bar in (A): 200 μm.",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, p53 shRNA, or p53 shRNA plus Flag-WDR63 Lysates from these cells were also analyzed by western blot (B).",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, p53 shRNA, or p53 shRNA plus Flag-WDR63 were subjected to transwell migration (C) The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bars 100 μm.",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing control shRNA, p53 shRNA, or p53 shRNA plus Flag-WDR63 were subjected to transwell invasion (D) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). **, P ˂ 0.01; ***, P ˂ 0.001; One-way ANOVA. Scale bars 100 μm.",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing either control shRNA or p53 shRNA were infected with lentiviruses expressing Flag-tagged full-length or truncated WDR63 proteins as indicated. Cells were then subjected to transwell migration (E) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; One-way ANOVA. Scale bar: 100 μm.",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "A549 cells expressing either control shRNA or p53 shRNA were infected with lentiviruses expressing Flag-tagged full-length or truncated WDR63 proteins as indicated. Cells were then subjected to transwell invasion (F) assays. The shown images are representative of three independent experiments. Data shown are mean ± SD (n=3). *, P ˂ 0.05; ***, P ˂ 0.001; One-way ANOVA. Scale bar: 100 μm.",
    "ncbi_link": "Flag: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "(G) A549 cells expressing control shRNA, p53 shRNA, or p53 shRNA plus Flag-WDR63 (each also expressing luciferase) were injected via tail vein into nude mice (n=6 for each group). Three weeks after injection, tumor formation was monitored by bioluminescence imaging. Data shown are mean ± SD; *, P ˂ 0.05; One-way ANOVA.",
    "ncbi_link": "Flag: 
luciferase: 
p53: 7157
WDR63: 126820"
  },
  {
    "caption": "Expression levels of the autophagosome marker LC3B-II were evaluated in wild-type (WT) and Ctns−/− fibroblasts by Western blot (WB). Data are representative of five different experiments with similar results.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WT and Ctns−/− fibroblasts were stained using LC3B antibodies and analyzed by fluorescence microscopy. The number of LC3B-positive puncta was quantified by the ImagePro software and normalized per area arbitrary units. Results are mean ± SEM (n = 27 WT and 24 Ctns−/− cells). ***P < 0.001 (unpaired t-test).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Immunofluorescence analysis of liver (C) and kidney (D) tissues from WT and Ctns−/−GFP-LC3 transgenic mice using anti-GFP antibodies. Quantification of LC3 puncta was obtained by counting the number of GFP-positive structures relative to the number of nuclei in the same field, using the ImagePro software. GFP-LC3 puncta were counted by analyzing 6 to 10 fields per tissue section (200-400 nuclei per field), in a total of 3 WT and 3 Ctns−/−mice expressing GFP-LC3. Results are mean ± SEM. In (C), **P = 0.0029; in (D), **P = 0.0025 (unpaired t-test). Scale bar: 5 μm.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Representative images of wild-type (WT) and Ctns−/− mouse fibroblasts transfected with the ptfLC3 vector under resting conditions (fed), or after serum starvation (Serum Starv.) in the presence or absence of the alkalinizing drug chloroquine (CQ). GFP and RFP staining was analyzed by confocal microscopy. Examples of red-only puncta (mature autophagosomes) are indicated with arrows. Scale bar: 5 μm.The percentage of mature autophagosomes (red-only vesicles) was calculated based on the ratio between the number of red-only puncta and the total number of autophagosomes (number of green and red + red-only puncta). The graph is representative of three different experiments with similar results. Results are mean ± SEM (n = 7 cells per condition). In addition to the experimental conditions shown in (A), the Aa/serum starvation condition is included.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WT and Ctns−/− fibroblasts under resting conditions were treated with 100 nM bafilomycin A (BafA) for 2 h and LC3B-II levels were analyzed by Western blot (WB).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Phosphorylation levels of the mTOR complex kinase 1 substrate S6K and LC3B-II levels in WT and Ctns−/− fibroblasts were measured by WB under resting conditions (−), withdrawal of both amino acids and serum (Aa/Ser. Starv.) and subsequent recovery by replacement of starvation medium with normal cell growth medium (Rec), in the presence or absence of 100 nM BafA for the indicated time.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WB analysis showing phosphorylation levels of the mTOR substrate S6K and expression of LC3B-II in resting or serum-starved WT,Ctns−/− and Ctns−/− fibroblasts expressing GFP-CTNS.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Analysis of the expression of endogenous SQSTM1 in wild-type or Ctns−/− mouse fibroblasts under fed (serum) or starved (15 h serum starvation) conditions. In these assays, 20 μg of total protein lysates were resolved by SDS-PAGE and analyzed by Western blot (WB; A). Equal loading was established by silver staining (B). Quantification (mean ± SEM) of five different areas of each silver-stained lane are shown in (C).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Degradation of long-lived proteins using metabolic labeling was performed as described in Supplementary Materials and Methods. The data represent the mean ± SEM of nine independent samples analyzed in three independent experiments. *P = 0.009 for WT and *P = 0.0013 for Ctns−/−, respectively. NS, not significant (unpaired t-test).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "The expression levels of the endogenous LAMP2A and LAMP1 proteins were analyzed in wild-type (WT) and Ctns−/−mousefibroblasts (A), kidney (B) and liverlysosomes (C) by Western blot. Quantitative densitometry analysis of immunoblots obtained from different experiments was performed by calculating the ratio between LAMP2A and actin signals in each lane. Results are mean ± SEM of four independent experiments with mousefibroblasts, 5 WT and 6 Ctns−/−mousekidneys, 3 WT and 3 Ctns−/−mouselivers (lysosomal extracts).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Comparative analysis of the amount of LAMP2A in wild-type or Ctns−/−liverlysosomes was performed using two different anti-LAMP2A antibodies. 15 μg of lysosomal proteins were loaded in each lane. Ab1, anti-LAMP2A antibody raised against the twelve amino acids of the cytosolic region of ratLAMP2A largely validated to recognize mouseLAMP2A but not other LAMP2 isoforms (Cuervo & Dice, 1996). Ab2, anti-LAMP2A Abcam Ab18528. Decreased lysosomalLAMP2A was evident using either antibody. LAMP1 was used as a loading control. Representative of two independent experiments with similar results.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Immunofluorescence analyses of endogenous LAMP1, LAMP2A (A, B), LAMP2B (C) and total LAMP2 (D) localization in wild-type (WT) and Ctns−/− mouse fibroblasts. (A) Confocal microscopy analysis. White arrows represent LAMP1-positive circular structures (lysosomes) which were visible in both WT and Ctns−/− cells. Colocalization of LAMP1 and LAMP2A was observed in WT fibroblasts (white arrows, merged panel) but rarely in Ctns−/− cells (red arrow). Most LAMP2A showed a punctate pattern and lack of colocalization with LAMP1 in Ctns−/− cells (arrowheads, lower panels). Scale bars: 5 μm. Inset scale bars: 2 μm.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Immunofluorescence analyses of endogenous LAMP1, LAMP2A (A, B), LAMP2B (C) and total LAMP2 (D) localization in wild-type (WT) and Ctns−/− mouse fibroblasts.(B) High-resolution stochastic optical reconstruction microscopy (STORM) analysis of the localization of LAMP1 and LAMP2A in wild-type and Ctns−/− cells. In Ctns−/− cells, LAMP2A was detected near (arrowheads, estimated distance > 50 nm) but not always adjacent (10-50 nm) to LAMP1 or at LAMP1-negative structures (arrows). Scale bar: 0.5 μm.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Immunofluorescence analyses of endogenous LAMP1, LAMP2A (A, B), LAMP2B (C) and total LAMP2 (D) localization in wild-type (WT) and Ctns−/− mouse fibroblasts. (C) Immunofluorescence showing colocalization of endogenous LAMP1 and LAMP2B in both wild-type and CTNS-deficient fibroblasts (arrows). Scale bar: 20 μm.",
    "ncbi_link": "Ctns: 83429
CTNS: 83429"
  },
  {
    "caption": "Immunofluorescence analyses of endogenous LAMP1, LAMP2A (A, B), LAMP2B (C) and total LAMP2 (D) localization in wild-type (WT) and Ctns−/− mouse fibroblasts. (D) Immunofluorescence analysis of LAMP1 and total LAMP2 (antibody ABL93 DSHB). Arrows show colocalization. Arrowheads show LAMP2-positive LAMP1-negative vesicles.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Immunofluorescence analyses of endogenous LAMP2A, ER (Grp78/94) (A), which is expanded in cystinotic cells (white arrow), VAMP7-positive vesicles (B) and Rab11a-positive structures (C) was performed using wild-type or Ctns−/− fibroblasts as described in Materials and Methods. At least 2 independent experiments were performed for each vesicular trafficking or ER marker. (B, C) Results are expressed as the percentage of LAMP2A that colocalizes with VAMP7 or Rab11. For Rab11/LAMP2A colocalization, 29 wild-type and 15 Ctns−/− cells were quantified. For VAMP7/LAMP2A colocalization (white arrows), 49 WT and 57 Ctns−/− cells were analyzed. Data are expressed as mean ± SEM. *P < 0.001 (unpaired t-test). Scale bars: 20 μm.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WT,Ctns−/− or Ctns−/− mouse fibroblasts treated for 20 h with either a combination of both leupeptin and chloroquine (CQ/Leu) or bafilomycin A (BafA) alone were fixed and immunostained with antibodies recognizing endogenous LAMP1 and LAMP2A proteins and samples were analyzed by confocal microscopy as described in Material and Methods. Lysosomal colocalization of LAMP1 and LAMP2A was evident in treated (middle lower and bottom panels) but not in untreated (middle upper panels) Ctns−/− cells. Scale bars: 5 μm. Inset scale bars: 2 μm.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Lysosomes were isolated from livers of starved wild-type (WT) and Ctns−/− mice as described in Supplementary Materials and Methods and incubated at 37°C for 30 min with the CMA substrate GAPDH, in the presence or absence of ATP (necessary for CMA) and protease inhibitors (Prot. Inhib.). A fraction of the CMA reactions was then mixed with sample buffer and boiled at 95°C for 5 min, followed by SDS-PAGE and GAPDH and LAMP1 immunoblotting.Quantitative densitometry analysis of CMA activity performed in independent experiments using lysosomes isolated from a total of 11 WT and 10 Ctns−/− mice. Results are mean ± SEM. ***P = 0.0005; **P = 0.0041; N.S., not significant (unpaired t-test).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "The ability of lysosomal proteases to mediate GAPDH degradation was assessed by incubating Triton X-100-treated WT and Ctns−/− lysosomes with GAPDH for 30 min in acidic reaction buffer and compared with input (reaction with no lysosomes). Quantitative densitometry analysis of independent reactions performed with lysosomes from a total of 9 WT and 9 Ctns−/− mice shows no significant difference in protease activity. Results are mean ± SEM.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WT and Ctns−/− mouse fibroblasts were treated with either 50 μM H2O2 or 1 mM paraquat (PQ) for 4 h and stained with (A) FITC-annexin V or (B) propidium iodide (PI) and analyzed by FACS. Results from 3 different experiments are shown as mean ± SEM. In (A), *P = 0.05; ***P = 0.0002. In (B), *P = 0.046; **P = 0.0065. Unpaired t-test.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "WT and Ctns−/− cells were treated as described above and samples analyzed by Western blot using antibodies recognizing cleaved (active) caspase 3. Data are representative of 2 independent experiments with similar results.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Cystine content in WT,Ctns−/−, cysteamine-treated Ctns−/− fibroblasts or Ctns−/− fibroblasts expressing GFP-CTNS was assessed by mass spectrometry.",
    "ncbi_link": "Ctns: 83429
CTNS: 83429"
  },
  {
    "caption": "WT, Ctns−/−, Ctns−/− fibroblasts treated with 1 mM cysteamine (48 h), or Ctns−/− fibroblasts expressing GFP-CTNS were fixed and stained with anti-LAMP1 and LAMP2A antibodies as indicated. For better visualization of LAMP1/LAMP2A colocalization, GFP-CTNS was pseudocolored as magenta and LAMP1 was pseudocolored as green (lower panels). Some lysosomes are indicated with arrows. Arrowheads indicate LAMP2A distribution to structures different from lysosomes (only observed in Ctns−/− cells and in cysteamine-treated Ctns−/− cells). Rescue of the LAMP2A localization to lysosomes was observed in Ctns−/− cells expressing GFP-CTNS. Scale bar: 2 μm.Quantification of the colocalization analysis described in (B). Calculation of the Pearson's colocalization coefficient was done by analyzing 113 WT, 251 Ctns−/−, 88 cysteamine-treated and 164 GFP-CTNS-expressing Ctns−/− cells, by using the ZEN 2010 software. Results are mean ± SEM. ***P < 0.001; NS, not significant (one-way ANOVA, Bonferroni's multiple comparisons test).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Cystine content in WT,Ctns−/− and cysteamine-treated Ctns−/− mouse livers was assessed by mass spectrometry. Results are mean ± SEM (n = 4). ***P < 0.001; **P = 0.0026 (one-way ANOVA, Bonferroni's multiple comparisons test).",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Western blot analysis of LAMP2A expression in lysosomes isolated from WT,Ctns−/− and cysteamine-treated Ctns−/− mouse livers.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "Lysosomes, isolated as in (B), were incubated with the CMA substrate GAPDH, and CMA activity was evaluated as in Fig8 and as described in Materials and Methods.Quantitative analysis of substrate degradation is expressed as percent of the residual amount of GAPDH in the full reaction relative to its amount in the presence of protease inhibitors. Results are mean ± SEM (n = 4). *P = 0.0126 for WT versus Ctns−/− and *P = 0.0436 for WT versus Ctns−/− + cysteamine; NS, not significant; unpaired t-test.",
    "ncbi_link": "Ctns: 83429"
  },
  {
    "caption": "A. Images of P4 (top) and P21 (bottom) Mpdz+/+ and Mpdz-/- mice. Arrowheads point to the domed foreheads of the latter.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "B. Mean weights of P18-P21 Mpdz+/+ and Mpdz-/- mice (n=8÷12, mean ± SD).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. Coronal, axial, and sagittal (top to bottom) PET images of P18-P21 Mpdz+/+ and Mpdz-/- mice. The emission intensity is shown as a 7-point temperature scale from black (0) to white (7).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "A. Coronal, sagittal, and axial (clockwise from top left corner image of each genotype) MR images of Mpdz+/+ and Mpdz-/- P18-P21 mice. Ventricles are pseudo-colored in red and 3D-reconstructed in the lower left panels.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "B. Means of total ventricle volumes and total brain volumes of Mpdz+/+ and Mpdz-/- mice (n=8, mean ± SD).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. A coronal HE-stained section (center) flanked by anatomically-corresponding coronal T2-weighted MR images of Mpdz-/- P18-P21 mice. Arrows or arrowheads show the match between the lateral ventricle CP in the HE section and in the MR images.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "A. Coronal HE-stained brain sections of a P18 Mpdz+/+ mouse (out of a total of three) showing the 3rd ventricle, and the proximal and distal sections of the aqueduct of Sylvius; these features are marked by arrows in the insets. B. The same, for P18 Mpdz-/- mice.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. Top views of brains of P7 Mpdz+/+ and Mpdz-/- mice that show the sites of Evans blue injection, and the midline planes (dashed line) sectioned to produce the sagittal images below. They show the extent of Evans blue spread in the ventricles and surrounding tissue (one out of three experiments). In, injection; LV, lateral ventricle; SA, Sylvian Aqueduct; V3, third ventricle; V4, fourth ventricle. Scale bars, 1 mm; insets, 0.25 mm.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "A. Immunofluorescence images of 10 μm-thick sections of CP from third ventricle villi of Mpdz+/+ and Mpdz-/- mice were immunolabeled as shown. The areas in the square frames are magnified in the bottom panels.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "CP sections from lateral ventricle villi immunolabeled for ZO1 (B) The images are representative of 2 Mpdz+/+ mice and 3 Mpdz-/- mice. Scale bars, top panels, 100 μm; bottom panels, 10 μm.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "CP sections from lateral ventricle villi immunolabeled for E-cadherin (E-cad; C). The images are representative of 2 Mpdz+/+ mice and 3 Mpdz-/- mice. Scale bars, top panels, 100 μm; bottom panels, 10 μm.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "A. TEM images of longitudinal sections of lateral ventricle CP villi of P18-P21 Mpdz+/+ and Mpdz-/- mice. Scale bar, 2 μm. B. A large number of voids of varying sizes was evident in the CPECs of Mpdz-/- mice. Higher magnification images of the areas in the rectangles are shown underneath the panels. Adherens junctions are denoted by horizontal lines and arrows; voids are indicated by arrows. Scale bar, 1 μm; insets, 200 nm.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. Triplicate images of tight junctions proximal to the apical faces of CPECs in Mpdz+/+ and Mpdz-/- mice. Scale bar, 100 nm",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "D. Mitochondria were smaller and frequently lacked large portions of their cristae. Autophagosomes are present in some of them (arrows). Scale bar, 200 nm. The images are representative of 2 Mpdz+/+ mice and 2 Mpdz-/- mice.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "E. Time course and standard deviations of the impedance of confluent hpCPEC monolayers that were transduced by either MPDZ or non-targeting (Ctrl) shRNA. Each record represents 4 wells. MPDZ immunoblot of each cell group is shown in the inset.",
    "ncbi_link": "MPDZ: 8777"
  },
  {
    "caption": "A. TEM images of CPEC sections from lateral ventricle villi of two Mpdz+/+ and two Mpdz-/- P14-P16 mice injected with HRP. The CPs were reacted with hydrogen peroxide and DAB ex-vivo. The dark particles are DAB deposits internalized by micropinocytosis. The magnified fields to the right show individual particles engulfed in macropinosomes. Note the layered structure of the particles, and the macropinosome that is open to the ventricular space in the Mpdz-/- section. Scale bars, 1 μm; insets, 100 nm. B. Mean number of engulfed DAB particles per cell in Mpdz+/+ and Mpdz-/- mice (mean ± SD, n=22).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. A CPEC section showing the engulfment of a DAB particle by its basal ruffles in the magnified field. Scale bars in panels C and D, 1 μm; insets, 200 nm. D. A CPEC section showing a preponderance of macropinosomes close to the apical face of the cell, and a magnified field that contains several macropinosomes. E. Mean numbers of DAB-containing macropinosomes close to the apical or basal sides of CPECs from Mpdz+/+ or Mpdz-/- mice (mean ± SD, n=20).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "A. Immunofluorescence images of 10 μm-thick sections from lateral ventricle CP villi of Mpdz+/+ and Mpdz-/- P14-P16 mice immunolabeled by anti-LDLR. Scale bars, 50 (top) and 25 (bottom) μm. B. Mean fluorescence intensities (normalized relative to the highest recorded intensity) per cell in several LDLR-immunolabeled CP sections (mean ± SD, n=101).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. Immunoblots showing the abundances of LDLR and MPDZ in hCPECs transduced by MPDZ-targeting or non-targeting shRNA. Mean abundances are quantified by densitometry of the LDLR bands, normalized relative to the β-actin bands (mean ± SD, n=3).",
    "ncbi_link": "MPDZ: 8777"
  },
  {
    "caption": "D. Fluorescence images of hCPECs transduced by either MPDZ or non-targeting (Ctrl) shRNA and immunolabeled by anti-LDLR either before (0 min) or after 8 min of constitutive endocytosis of LDLR. The histograms below show the mean fluorescence intensities per hCPEC in each cell group, normalized relative to the highest recorded intensity (mean ± SD, n=41÷53).",
    "ncbi_link": "MPDZ: 8777"
  },
  {
    "caption": "A. Mean protein concentration in the CSF of Mpdz+/+ and Mpdz-/- P14-P21 mice (mean ± SD, n=2÷3).",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "B. Volcano plot showing that the protein contents in sera of P15-P21 Mpdz+/+ and Mpdz-/- mice are similar to each other.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "C. A volcano plot showing that 23 proteins are at least two-fold significantly more abundant in the CSF of P15-21 Mpdz-/- mice (red circles, protein names are indicated) whereas only two proteins were more abundant in the CSF of Mpdz+/+ mice (green circles). The CSF composition was analyzed in 3 Mpdz-/- and 3 Mpdz+/+ mice.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "D. Images of 10 μm-thick sections from lateral ventricle CP villi of Mpdz+/+ and Mpdz-/- mice, immunolabeled for Nkcc1. The areas in the marked squares are magnified below. Scale bars, top, 50 μm, bottom 20 μm.",
    "ncbi_link": "Mpdz: 17475"
  },
  {
    "caption": "Kaplan Meier survival curve of N2, odr-3(n2150) and odr-3(n2046) worms on partial lawn of P. aeruginosa at 25°C.   Kaplan Meier survival curve of N2, odr-3(n2150) and odr-3(n2046)   worms on full lawn of P. aeruginosa at 25°C.",
    "ncbi_link": "odr-3: 179806"
  },
  {
    "caption": "Real time PCR analysis of irg-1, irg-2 and irg-3 genes in N2, odr-3(n2150) and odr-3(n2046) worms exposed to 1-undecene odor upon respective naive worms. n = 3. * P ≤ 0.05, ** P ≤ 0.01 as determined by two-tailed unpaired t-test. Error bars indicate SEM. Real time PCR analysis of irg-1, irg-2 and irg-3 genes in N2, lim-4(ky403) and lim-4(yz12) worms exposed to 1-undecene odor upon respective naive worms. n = 3. * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001 as determined by two-tailed unpaired t-test. Error bars indicate SEM.",
    "ncbi_link": "irg-1: 182379
irg-2: 183619
irg-3: 178726
lim-4: 180672
odr-3: 179806"
  },
  {
    "caption": "(a,b) Survival of wild-type (Oregon R), yw, PGRP-LE112, PGRP-LC7454 and PGRP-LE112,PGRP-LC7454 flies after injection of wild-type L. monocytogenes (a) or Δhly L. monocytogenes (b) at 28 °C.",
    "ncbi_link": "hly: 12515457
PGRP-LC: 39063
PGRP-LE: 32534"
  },
  {
    "caption": "(c) Survival of wild-type, yw and PGRP-LE112 flies, as well as flies treated with RNAi targeting PGRP-LE with the hml-Gal4 driver (hml-Gal4>PGRP-LE RNAi) and PGRP-LE112 flies with hml-Gal4-driven PGRP-LE expression (PGRP-LE112,hml-Gal4>PGRP-LE), after injection of wild-type L. monocytogenes at 28 °C. NS, not significant; *, P 0.01 (Wilcoxon-Mann-Whitney test): P = 0.0006, 0.0043 or 0.0043, for yw versus PGRP-LE112, PGRP-LC7454 or PGRP-LE112,PGRP-LC7454, respectively (a); P = 0.0095, for yw versus RNAi targeting PGRP-LE (c). Data represent the average of four independent experiments with over 30 flies of each genotype examined at the same time.",
    "ncbi_link": "Gal4: 
hml: 39529
PGRP-LC: 39063
PGRP-LE: 32534"
  },
  {
    "caption": "(a) Microscopy of hemocytes from third instar larvae cultured ex vivo and infected with wild-type L. monocytogenes. Hemocyte nuclei (filled arrowhead) and DNA of L. monocytogenes (open arrowhead) are visualized by DAPI staining (blue or white); the actin cytoskeleton is stained with rhodamine-labeled phalloidin (red). hml-Gal4>Atg5IR, expression of an inverted repeat sequence of Atg5 to induce RNAi against Atg5. Scale bars, 10 μm.",
    "ncbi_link": "Gal4: 
Atg5: 31666
hml: 39529"
  },
  {
    "caption": "(b) Intracellular wild-type L. monocytogenes (WT Lm) or Δhly L. monocytogenes (Δhly Lm) counted manually in DAPI-stained infected hemocytes. LE112,hml>LE, hml-Gal4-driven expression of PGRP-LE in PGRP-LE112 hemocytes; imd1, imd; RelE20, RelishE20; hml>Atg5IR, inverted repeat sequence described in a; w, hml>Atg1, hml-Gal4-driven expression of Atg1 in w hemocytes; LE112,hml>Atg1, hml-Gal4-driven expression of Atg1 in PGRP-LE112 hemocytes; PGRP-LE112+rap, PGRP-LE112 hemocytes plus rapamycin. *, P 0.001, compared with wild type (t-test). Data are representative of four experiments (a) or at least three independent experiments (b; error bars, s.d. of triplicate measurements).",
    "ncbi_link": "Gal4: 
Atg1: 39454
Atg5: 31666
hly: 12515457
hml: 39529
imd: 44339
PGRP-LE: 32534
Rel: 41087
Relish: 41087"
  },
  {
    "caption": "Survival of yw flies, PGRP-LE112 flies, flies treated with Atg5-directed RNAi (hml-Gal4>Atg5IR) and control flies carrying hml-Gal4 (hml-Gal4>GFP), after injection of wild-type L. monocytogenes (a), Δhly L. monocytogenes (b) or E. carotovora (c) into adult flies. *, P 0.01 (Wilcoxon-Mann-Whitney test): P = 0.0024, Atg5-directed RNAi versus control (a), P = 0.0007, PGRP-LE112 versus control (a); P = 0.0055, PGRP-LC7454 versus yw (c). Data represent the average of four independent experiments.",
    "ncbi_link": "Gal4: 
Atg5: 31666
hly: 12515457
hml: 39529
PGRP-LC: 39063
PGRP-LE: 32534"
  },
  {
    "caption": "(a) Growth of L. monocytogenes in S2 cells (S2) or S2 cells expressing PGRP-LE (S2-LE) transfected with double-stranded RNA (RNAi) specific for Atg5, Rel or Dif and dl (Dif-dl) and infected for 1.5 h with wild-type or Δhly L. monocytogenes, followed by 6 h of incubation in medium containing CuSO4 and gentamicin, quantified by plate assay of colony-forming units. *, P 0.001 (t-test). Data are representative of two independent experiments (error bars, s.d.).",
    "ncbi_link": "Atg5: 31666
Dif: 35045
dl: 35047
hly: 12515457
PGRP-LE: 32534
Rel: 41087"
  },
  {
    "caption": "(b,c) Fluorescence confocal microscopy of the localization of PGRP-LE together with wild-type L. monocytogenes in S2 cells engineered to express YFP-PGRP-LE (YFP-LE) and infected for 0.5 h with wild-type L. monocytogenes (b) or Δhly L. monocytogenes (c), followed by 1 h of incubation in gentamicin-containing medium, then DAPI staining. Merge, YFP-PGRP-LE (green) and DAPI (magenta). Filled arrowheads indicate L. monocytogenes; open arrowhead indicates accumulation of YFP-PGRP-LE around the bacteria. Scale bars, 5 μm. Data are representative of three experiments.",
    "ncbi_link": "hly: 12515457
PGRP-LE: 32534"
  },
  {
    "caption": "(a) Dot- or ring-shaped GFP-LC3 (LC3 dot) signals in S2 cells expressing both PGRP-LE and GFP-LC3 under the control of an actin promoter (PGRP-LE GFP-LC3) or GFP-LC3 alone (GFP-LC3) after infection with wild-type or Δhly L. monocytogenes or after 1.5 h of incubation with 5 μM rapamycin (rap). -, no infection.",
    "ncbi_link": "actin: 
LC3: 
hly: 12515457
PGRP-LE: 32534"
  },
  {
    "caption": "(c) Confocal microscopy of S2 cells expressing PGRP-LE and GFP-LC3 (green) infected with wild-type L. monocytogenes and stained with DAPI (magenta). Arrow indicates colocalization of GFP-LC3 and L. monocytogenes.",
    "ncbi_link": "LC3: 
PGRP-LE: 32534"
  },
  {
    "caption": "(e-i) Ultrastructural analysis of S2 cells expressing PGRP-LE and GFP-LC3 and infected with wild-type L. monocytogenes. (e,f) Fluorescence microscopy (e) and electron microscopy (f) of cells expressing GFP-LC3 (green) and stained with DAPI (magenta). (g) Enlargement of a bacteria-containing vacuole from f. (h,i) Enlargement of the fields outlined in g. Arrows indicate double-membrane structure that surrounds the bacteria; arrowheads indicate an endoplasmic reticulum-like membrane.",
    "ncbi_link": "PGRP-LE: 32534"
  },
  {
    "caption": "(j) Confocal microscopy of hemocytes infected with wild-type L. monocytogenes. Green, GFP-LC3; magenta, DAPI. Arrow indicates colocalization of GFP-LC3 and L. monocytogenes.",
    "ncbi_link": "LC3: "
  },
  {
    "caption": "(k) Dot- or ring-shaped GFP-LC3 signals in ex vivo-cultured hemocytes expressing GFP-LC3 (infection and treatment, horizontal axis).",
    "ncbi_link": "LC3: "
  },
  {
    "caption": "(m) GFP-LC3 dots in S2 cells expressing PGRP-LE and GFP-LC3 and treated with RNAi (below graph) and infected for 0.5 h with L. monocytogenes then incubated for 1 h in gentamicin-containing medium; dots quantified by confocal microscopy. Scale bars, 5 μm (c,j), 1 μm (e,f) or 500 nm (g). *, P 0.001 (t-test). Data are representative of three (a,k,m), two (b,e-i), six (c), four (d) or five (j,l) experiments (error bars, s.d. of triplicate measurements (a,b,l) or at least triplicate measurements (m)).",
    "ncbi_link": "PGRP-LE: 32534"
  },
  {
    "caption": "(a) GFP-LC3 dots in S2 cells expressing GFP-LC3 alone or PGRP-LE and GFP-LC3, treated for 2 h with TCT (100 nM), highly purified DAP-type PGN from L. plantarum (DAP; 100 μg/ml) or lysine-type PGN from S. epidermidis (Lys).",
    "ncbi_link": "PGRP-LE: 32534"
  },
  {
    "caption": "(b) Dot- or ring-shaped GFP-LC3 signals in hemocytes after infection with wild-type or Δhly L. monocytogenes or treatment with rapamycin (5 μM) or with TCT, DAP-type PGN or lysine-type PGN. *, P 0.001 (t-test). Data are representative of two independent experiments (error bars, s.d.).",
    "ncbi_link": "hly: 12515457"
  },
  {
    "caption": "(B, C) HCT116, PKcs-/-, and Lig4-/- cells were subjected to Agilent Seahorse XFe24 analyzer to measure oxidative phosphorylation (B) via the oxygen consumption rate (OCR) and glycolysis (C) via the extracellular acidification rate (ECAR).",
    "ncbi_link": "Lig4: 3981
PKcs: 5591"
  },
  {
    "caption": "(A) HeLa cells expressing Flag-tagged ANT1-3 were subjected to Co-IP using anti-Flag antibody, then analyzed by western blot as indicated.",
    "ncbi_link": "Flag: 
ANT1: 291"
  },
  {
    "caption": "(E) HeLa cells expressing Flag-tagged VDAC1-3 were subjected to Co-IP using anti-Flag antibody and analyzed by western blot as indicated.",
    "ncbi_link": "Flag: 
VDAC1: 7416"
  },
  {
    "caption": "(F) PLA analysis show that the interaction between DNA-PKcs and Flag-ANT2 was disrupted by knockdown of VDAC2, but not VDAC1 or VDAC3. Quantification shown on the right. ***, P < 0.001. Data information: The bar graphs were generated from three independent biological replicates analyses; data are represented as mean ± SD. Statistical significance was established using a two-way analysis of variance (ANOVA, *, P < 0.05; **, P < 0.01; ***, P < 0.001).",
    "ncbi_link": "VDAC1: 7416
VDAC2: 7417
VDAC3: 7419"
  },
  {
    "caption": "(A, B) HCT116, DNA-PKcs-/-, and Ligase 4-/- cells were subjected to ADP-ATP exchange assay using MgGreen 5K+ fluorescent dye. The exchange was stimulated by 5mM ADP and halted by ANTs inhibitor carboxyatractyloside (cATR). Normalized MgGreen 5K+ fluorescence was first measured to indicate changes in free magnesium concentration (A). The decreased free magnesium concentration was converted into efflux of ATP ([ATP]e, mM) after the addition of ADP (B). Bar graph on the right shows the normalized MgGreen 5K+ fluorescence and efflux of ATP concentration after ADP until the reaction was stopped by cATR treatment.",
    "ncbi_link": "Ligase 4: 3981
DNA-PKcs: 5591"
  },
  {
    "caption": "(F) shGFP and shATM pair of HeLa (Right) or MCF7 (Left) cells were subjected to an ADP-ATP exchange assay using MgGreen 5K+ fluorescent dye.",
    "ncbi_link": "GFP: 
ATM: 472"
  },
  {
    "caption": "(A) Western blot results show attenuation of ANT2 protein level in DNA-PKcs-deficient and depleted cells.",
    "ncbi_link": "DNA-PKcs: 5591"
  },
  {
    "caption": "(L) Treatment with VDAC2 siRNA in Hela cells attenuated ADP-ATP exchange. Bar graph on the right shows the efflux of ATP concentration after adding ADP.",
    "ncbi_link": "VDAC2: 7417"
  },
  {
    "caption": "(A, B) Paired shGFP and shATM HeLa (A) and MCF7 cells (B) were subjected to ADP-ATP exchange assay using MgGreen 5K+ fluorescent dye. The decreased free magnesium concentration was converted into efflux of ATP ([ATP]e, mM) after the addition of ADP. The bar graphs were generated from three independent biological replicates analyses;",
    "ncbi_link": "GFP: 
ATM: 472"
  },
  {
    "caption": ", D) PLA analysis show that the interaction between DNA-PKcs and Flag-ANT2 in HeLa (C) and MCF7 (D) was temporarily disrupted by treatment of 10Gy IR. Knockdown of ATM disrupted the dissociation. Quantification shown on the right. The bar graphs were generated from three independent biological replicates analyses",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": "(E) HeLa cells expressing Flag-tagged VDAC2 and V5-tagged ANT2 were subjected to Co-IP using anti-Flag antibody and analyzed by western blot as indicated. ANT2, but not VDAC2, temporarily dissociated from DNA-PKcs after treatment of 10Gy IR. ATM knockdown and inhibition (AZD1390, 10 nM) disrupted the dissociation.",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": "(A) Western blot results show knockdown of ATM attenuated 100 μM H2O2 induced T2609 and T2647 phosphorylation of DNA-PKcs in HeLa cells.",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": "(C,D) PLA Analysis shows that the interaction between DNA-PKcs and ANT2 in MEF cells was temporarily disrupted by treatment of 10Gy IR. DNA-PKcs3A/3A remained interaction with ANT2 after IR. The bar graphs were generated from three independent biological replicates analyses; data are represented as mean ± SD. Statistical significance was established using a two-way analysis of variance (ANOVA, *, P < 0.05; **, P < 0.01; ***, P < 0.001).",
    "ncbi_link": "DNA-PKcs: 19090"
  },
  {
    "caption": "D Selected examples of DEG across disease stages from clusters 2-5 defined in (C). In (D) each donor is represented by an individual point (no COPD n=3, COPD I n=3, COPD II-IV n=5), the group mean is shown as black dot and the error bar represents the standard deviation. In (D) FDRs and log2(fold-changes) (in A) were calculated using DESeq2, which uses a negative binominal GLM (generalized linear model) and Wald statistics. *: FDR <0.05; **: FDR <0.01; ***: FDR <0.001. The specific statistically significant FDR values are the following: RAD18 in COPD II-IV= 0.000434; ADAMTSL1 in COPD II-IV=0.02771; STEPA3 in COPD I= 0.04219 and in COPD II-IV= 0.001272; BMP4 in COPD II-IV= 0.0000535. ",
    "ncbi_link": "ADAMTSL1: 92949
BMP4: 652
RAD18: 56852
STEPA3: 55240"
  },
  {
    "caption": "B-H Live confocal images of ddaC neurons expressing mCD8-GFP by ppk-Gal4 at WP stage or 16 h APF. Neurons expressing efa6 RNAi #1-#3 (C-E), efa612 mutant MARCM clones (F), and efa612/GX6w- transheterozygous mutant neurons (G) showed consistent dendrite pruning defects at 16 h APF, as compared to the wild-type neurons (B). The dendrite pruning defects were fully rescued when overexpressing full-length Efa6 in the efa612 mutant clones (H). Red arrowheads point to the ddaC somas.",
    "ncbi_link": "efa6: 42665
Efa6: 42665
Gal4: 855828
ppk: 34843"
  },
  {
    "caption": "Live confocal images of efa612/GX6w- mutant ddaC neurons at WP stage and 16 h APF. Expression of Efa6FL (C) rescued the pruning defects in efa612/GX6w- mutant ddaC neurons (B). Red arrowheads point to the ddaC somas.",
    "ncbi_link": "efa6: 42665
Efa6: 42665"
  },
  {
    "caption": "Live confocal images of efa612/GX6w- mutant ddaC neurons at WP stage and 16 h APF. Expression of Efa6Nterm (D), Efa6ΔPH (F) and Efa6Nterm+CAAX (H), but not Efa6Cterm (E) or Efa6ΔMTED (G), rescued the pruning defects in efa612/GX6w- mutant ddaC neurons Red arrowheads point to the ddaC somas. I-J Quantification of dendrite severing defects and unpruned dendrite lengths at 16 h APF.",
    "ncbi_link": "efa6: 42665
Efa6: 42665"
  },
  {
    "caption": "A-D Live confocal images of ddaC neurons at WP stage and 7 h APF. Efa6FL or Efa6Nterm-overexpressing neurons (B, C) showed precocious pruning phenotype at 7 h APF, compared to the control and Efa6ΔMTED-overexpressing neurons (A, D) in which most dendrites remained attached to the soma at the same time point. Red arrowheads point to the ddaC somas. Dorsal dendrites are marked by red arrows. E Quantification of precocious pruning defects as indicated by the percentage of dorsal dendrites attached to the soma at 7 h APF. ",
    "ncbi_link": "Efa6: 42665"
  },
  {
    "caption": "F-I Confocal images of da sensory neurons expressing Efa6-Ki-GFP (F), or UAS-Efa6-GFP driven by ppk-Gal4 (H) were co-stained with GFP (Green) and Nrg (Magenta) at wL3 stage. (G, I) Confocal images of the epidermal cells expressing Efa6-Ki-GFP (G) or UAS-Efa6-GFP driven by A58-Gal4 (I) were co-stained with GFP (Green) and Dlg (Magenta) at wL3 stage. The ddaC soma is marked by dashed lines.",
    "ncbi_link": "A58: 
GFP: 
Efa6: 42665
Gal4: 855828
ppk: 34843"
  },
  {
    "caption": "A-F Representative kymographs of EB1-GFP comets in the proximal dendrites of ddaC neurons at 96 h AEL. The horizontal arrow indicates the direction toward the soma, and the vertical arrow indicates the time. In contrast to the wild type (A), the number of EB1-GFP comets was significantly increased in efa612/GX6w- mutant neurons (B). The comet length and speed were significantly decreased in Efa6FL- and Efa6Nterm-overexpressing neurons, but not in Efa6ΔMTED-overexpression neurons (C-F).",
    "ncbi_link": "efa6: 42665
Efa6: 42665"
  },
  {
    "caption": "A-C Live confocal images of ddaC dendrites expressing tdEOS::α-tubulin driven by ppk-Gal4. The microtubule turnover rate was significantly reduced in efa6 RNAi neurons at wL3 (A, right panels) and WP stages (B, right panels), and increased in Efa6-overexpressing neurons at wL3 stage (C, right panels), compared to the control neurons (A-C, left panels).",
    "ncbi_link": "efa6: 42665
Efa6: 42665
Gal4: 855828
ppk: 34843"
  },
  {
    "caption": "A-H Live confocal images of ddaC neurons at WP stage and 16 h APF. Treatment with colchicine significantly suppressed the pruning defects of efa6 RNAi neurons (A, B), while taxol treatment enhanced the pruning defects (C, D). Removal of one copy of γTub23C (F) or expression of γTub23C RNAi (H) almost fully rescued the dendrite pruning defects in efa6 mutant (E) or RNAi neurons (G), respectively. Red arrowheads point to the ddaC somas.",
    "ncbi_link": "efa6: 42665
γTub23C: 33501"
  },
  {
    "caption": "A-F Live confocal images of ddaC neurons at WP stage and 16 h APF. stai RNAi neurons (B), staiSK7 (C), staiKO (D) mutant MARCM clones showed similar dendrite pruning defects, compared to the wild-type ddaC neurons (A). Double RNAi of stai and efa6 significantly enhanced the dendrite pruning defects (E), compared to their individual RNAi knockdown. Expression of stai RNAi in efa612/GX6w- mutant background also significantly enhanced the dendrite pruning defects (F), compared to the RNAi or mutant alone. Red arrowheads point to the ddaC somas.",
    "ncbi_link": "efa6: 42665
stai: 33863"
  },
  {
    "caption": "I-L Representative kymographs of EB1-GFP comets driven by Gal44-77 in the proximal dendrites of ddaC neurons at 96 h AEL.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "A, Treatment of PRL2 with a synthetic substrate leads to complete phosphorylation of the catalytic residue, cysteine 101. Recombinant PRL2 was treated with 3-O-methylfluorescein phosphate (OMFP) and analyzed by SDS-PAGE with the Phos-tag reagent. Phosphocysteine is hydrolyzed by boiling.",
    "ncbi_link": "PRL2: 8073"
  },
  {
    "caption": "A, Mutations in the CBS-pair loop of CNNM4 prevent binding to PRL3. Lysates of COS7 cells transfected with the indicated constructs were subjected to immunoprecipitation (IP) and immunoblotting (IB) with the indicated antibodies.",
    "ncbi_link": "CNNM4: 26504"
  },
  {
    "caption": "B & C, Wild-type CNNM4-dependent magnesium efflux is inhibited by co-transfection by PRL3 but the efflux by the CNNM4 D485A mutant, which is unable to bind PRL3, is resistant to inhibition. HEK293 cells transfected with the indicated constructs were loaded with Magnesium Green and Mg2+ removed from the medium at the indicated time point (arrowhead). The means of relative fluorescence intensities of 10 cells are graphed as a function of time in panel B and the mean and s.e.m. at 5 min plotted in panel C. P-values were calculated using one way ANOVA followed by Bonferroni's multiple comparison test. n.s., not significant.",
    "ncbi_link": "CNNM4: 26504"
  },
  {
    "caption": "B & C, Wild-type CNNM4-dependent magnesium efflux is inhibited by co-transfection by PRL3 but the efflux by the CNNM4 D485A mutant, which is unable to bind PRL3, is resistant to inhibition. HEK293 cells transfected with the indicated constructs were loaded with Magnesium Green and Mg2+ removed from the medium at the indicated time point (arrowhead). The means of relative fluorescence intensities of 10 cells are graphed as a function of time in panel B and the mean and s.e.m. at 5 min plotted in panel C. P-values were calculated using one way ANOVA followed by Bonferroni's multiple comparison test. n.s., not significant.",
    "ncbi_link": "CNNM4: 26504"
  },
  {
    "caption": "C, Co-immunoprecipitation of Myc-PRL by FLAG-CNNMs shows only the unphosphorylated forms of PRL1 binds CNNM4.",
    "ncbi_link": "CNNM4: 26504"
  },
  {
    "caption": "(G) EGFR protein expression in EGFR knockout HBMEC using CRISPR/Cas9 (left panel) and relative invasion frequency of 8 meningitis isolates of GBS strains in EGFR knockout and control HBMEC (right panel). From left to right, p value of K79 is 0.0059, p value of K160 is 0.00024, p value of K161 is 0.00080, p value of K181 is 0.00042, p value of K226 is 0.00011, p value of K237 is 0.00072, p value of K238 is 0.0093, p value of P539 is 0.00013 (right panel).",
    "ncbi_link": "Cas9: 57852564
EGFR: 1956"
  },
  {
    "caption": "(H) GBS strain K79 traversal of HBMEC monolayer was significantly decreased in EGFR knockout HBMEC compare to control HBMEC.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(I) Bacterial counts recovered from the blood and brain of EGFR conditional knockout (n = 5) and control mice (n = 5) 1 h after intravenous inoculation with strain K79.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "(A) Tyrosine phosphorylation of EGFR in HBMEC pre-treated with 20 μM S1P2 antagonist (JTE-013) or vehicle control and infected with GBS strain K79 infection for 60 min. EGFR phosphorylation in control and S1P2 knockout HBMEC infected with K79.",
    "ncbi_link": "S1P2: 9294"
  },
  {
    "caption": "(C) S1P2 protein expression in S1P2 knockout HBMEC using CRISPR/Cas9 (left panel). Relative invasion frequency of 8 meningitis isolates of GBS in S1P2 knockout HBMEC. From left to right, p value of K79 is 0.0018, p value of K160 is 0.0091, p value of K161 is 0.0054, p value of K181 is 0.00040, p value of K226 is 0.00032, p value of K237 is 0.040, p value of K238 is 0.041 and p value of P539 is 0.0025.",
    "ncbi_link": "Cas9: 57852564
S1P2: 9294"
  },
  {
    "caption": "(D) GBS strain K79 traversal of HBMEC monolayer was significantly decreased in S1P2 knockout HBMEC compare to control.",
    "ncbi_link": "S1P2: 9294"
  },
  {
    "caption": "(E) Bacterial counts recovered from the blood and brain of wild type (n = 5) and S1P2-/- mice (n = 5) infected with strain K79 for 1h.",
    "ncbi_link": "S1P2: 14739"
  },
  {
    "caption": "(A) Serine phosphorylation of cPLA2α in response to GBS strain K79 in HBMEC pretreated with gefitinib or vehicle control and in EGFR knockout HBMEC.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(B) Serine phosphorylation of cPLA2α in response to GBS strain K79 in control, EGFR knockout and S1P2 knockout HBMEC.",
    "ncbi_link": "EGFR: 1956
S1P2: 9294"
  },
  {
    "caption": "(C) Bacterial counts recovered from the blood and brain in wild type mice (n = 5) and CysLT2-/- mice (n = 5) infected with strain K79 for 1h.",
    "ncbi_link": "CysLT2: 70086"
  },
  {
    "caption": "(D) CysLT1 protein expression in CysLT1 knockdown HBMEC using shRNA (left panel) and relative invasion frequency of 8 GBS isolates in CysLT1 knockdown and control HBMEC. t-test. From left to right, p value of K79 is 0.0039, p value of K160 is 0.0082, p value of K161 is 0.00091, p value of K181 is 0.0087, p value of K226 is 0.00020, p value of K237 is 0.0039, p value of K238 is 0.00066, p value of P539 is 1.76E-05 (right panel).",
    "ncbi_link": "CysLT1: 10800"
  },
  {
    "caption": "(E) GBS strain K79 traversal of HBMEC monolayer was significantly decreased in CysLT1 knockdown HBMEC compare to control.",
    "ncbi_link": "CysLT1: 10800"
  },
  {
    "caption": "(F) Bacterial counts recovered from the blood and brain in wild type mice (n = 7) and CysLT1-/- mice (n = 7) infected with strain K79 for 1h.",
    "ncbi_link": "CysLT1: 58861"
  },
  {
    "caption": "(G) Ezrin protein expression in ezrin knockdown HBMEC using shRNA (left panel) and relative invasion frequency of GBS strain K79 in ezrin knockdown and control HBMEC (right panel).",
    "ncbi_link": "ezrin: 7430"
  },
  {
    "caption": "(J) Intracellular K79 co-localization with EGFR and ezrin in control and S1P2 knockout HBMEC (as shown by arrows, cyan). Percentage of co-localization was calculated by counting numbers of all GBS and co-localized intracellular GBS from at least three representative fields, and expressing as numbers of co-localized GBS/all GBS x 100.",
    "ncbi_link": "S1P2: 9294"
  },
  {
    "caption": "A. GAPDH smFISH and IF analysis using anti-G3BP antibody (G3BP) and anti-Dcp1b antibody (DCP1) in A549 cells (RL-WT) or A549 RL-KO cells either mock transfected (mock) or transfected with poly(I:C) (PIC) for 5 hours. Scale bar 10 microns. B. Graph of the fraction of G3BP foci with different volumes in PIC treated RL-WT and RL-KO cells. C. Number of DCP1 foci per cell in PIC treated RL-WT and RL-KO cells relative to the number in mock treated cells. D. Average volume of individual Dcp1 foci in mock and PIC treated RL-WT and RL-KO cells.",
    "ncbi_link": "GAPDH: 2597
RL: 6041"
  },
  {
    "caption": "A. Western analysis of nuclear (N) or cytoplasmic (C) fractions from whole cell lysates (W) from A549 cells (RL WT), RNase L knock out A549 cells (RL KO), or A549 cells with either wild-type RNase L (NLS-RL-WT) or RNase L-R667A (NLS-RL-CM) fused to a nuclear localization signal sequence. Short and long exposure with anti-RL antibody. GAPDH protein used as cytoplasmic marker. Histone H3 protein used as nuclear marker. B. Graph depicting the fraction of RNase L found in the nucleus or cytoplasm. Mean and SEM of two experiments with individual experiment values plotted.",
    "ncbi_link": "RL: 6041
RNase L: 6041"
  },
  {
    "caption": "C. FISH with probes to GAPDH mRNA or oligo(dT) to detect poly(A)+ RNA in A549 cells without or with either NLS-RL-WT or NLS-RL-CM either mock transfected or transfected with poly(I:C) for 4 hours. Scale bar 5 micron.",
    "ncbi_link": "GAPDH: 2597
RL: 6041"
  },
  {
    "caption": "Analysis of nuclear RNA granules in A549 cells with RNase L targeted to the nucleus (NLS-RL-WT) either mock transfected or treated with poly(I:C) (PIC) for 4 to 5 hours. A. FISH analysis to detect poly(A)+ RNA and nucleolar-localized snoRD3A RNA. IF analysis to detect nucleolar granular component protein nucleophosmin (NPM1). B. Graph of the mean and value of the average volume of individual snoRD3A foci in nuclei. 17 nuclei mock treated cells, 31 nuclei PIC treated cells. C. Fraction of nuclei with NPM1 protein enriched in ring structures classified as granular component assemblies or dispersed in nucleoplasm. 17 nuclei mock treated cells, 31 nuclei PIC treated cells.",
    "ncbi_link": "RL: 6041
RNase L: 6041
snoRD3A: 780851"
  },
  {
    "caption": "Analysis of nuclear RNA granules in A549 cells with RNase L targeted to the nucleus (NLS-RL-WT) either mock transfected or treated with poly(I:C) (PIC) for 4 to 5 hours. D. IF analysis to detect dense fibrillar component protein, ribosome processing factor 1 (RPF1). E. Graph of the mean and value of the average volume of individual snoRD3A foci in nuclei. 43 nuclei mock treated cells, 69 nuclei PIC treated cells. F. Graph of the mean and value of the average volume of RPF1 foci in 43 mock treated cells and 69 nuclei PIC treated cells.",
    "ncbi_link": "RL: 6041
RNase L: 6041
snoRD3A: 780851"
  },
  {
    "caption": "Analysis of nuclear RNA granules in A549 cells with RNase L targeted to the nucleus (NLS-RL-WT) either mock transfected or treated with poly(I:C) (PIC) for 4 to 5 hours. G. FISH analysis to detect poly(A)+ RNA and nuclear speckle-localized MALAT1 RNA and IF analysis with anti-sc35 antibody to detect nuclear speckle protein SRRM2. H. Graph of the mean and value of the intensity of MALAT1 signal divided by the nuclear volume of individual nuclei. 51 nuclei mock treated cells, 56 nuclei PIC treated cells. I. Graph of the median and value of the volume of individual SRRM2 foci in nuclei. Mock 1526 SRRM2 foci in 51 nuclei. PIC 136 SRRM2 foci in 20 nuclei that contain <10 SRRM2 foci.",
    "ncbi_link": "MALAT1: 378938
RL: 6041
RNase L: 6041"
  },
  {
    "caption": "Analysis of nuclear RNA granules in A549 cells with RNase L targeted to the nucleus (NLS-RL-WT) either mock transfected or treated with poly(I:C) (PIC) for 4 to 5 hours. J. FISH analysis to detect poly(A)+ RNA and IF analysis to detect Cajal body protein coilin. K. Graph depicting the fraction of nuclei in mock and PIC treated cells with decreased oligo(dT) with different distributions of coilin protein. 90 nuclei in mock treated cells, 192 nuclei in PIC treated cells.",
    "ncbi_link": "RL: 6041
RNase L: 6041"
  },
  {
    "caption": "Analysis of A549 cells with NLS-RL-WT or NLS-RL-CM either mock transfected or treated with poly(I:C) (PIC) for 5 hours. A. FISH analysis to detect poly(A)+ RNA and IF analysis against FUS protein. Images are a single 0.2 micron Z section.",
    "ncbi_link": "RL: 6041"
  },
  {
    "caption": "Analysis of A549 cells with NLS-RL-WT or NLS-RL-CM either mock transfected or treated with poly(I:C) (PIC) for 5 hours. B. Graph depicting the fraction of nuclei with FUS dispersed in the nucleoplasm or in foci in cells with reduced nuclear oligo(dT) signal. All the nuclei (total) in which nuclear RNA was degraded (N=64) or the same nuclei classified as to whether or not they contained residual poly(A) foci. Nuclei with poly(A) foci (N=14). Nuclei without poly(A) foci (N=50).",
    "ncbi_link": "RL: 6041"
  },
  {
    "caption": "Analysis of A549 cells with NLS-RL-WT either mock transfected or treated with poly(I:C) (PIC) for 5 hours. C. FISH analysis to detect poly(A)+ RNA and IF analysis against mediator complex protein, MED1, to detect super-enhancer condensates. D. Number of MED1 foci in mock and PIC treated NLS-RL-WT cells. E. Average volume of individual MED1 foci in mock and PIC treated NLS-RL-WT cells.",
    "ncbi_link": "RL: 6041"
  },
  {
    "caption": "Analysis of A549 cells with NLS-RL-WT either mock transfected or treated with poly(I:C) (PIC) for 5 hours. F. FISH analysis to detect poly(A)+ RNA and IF analysis against BRD4, to detect super-enhancer condensates. G. Number of BRD4 foci in mock and PIC treated NLS-RL-WT cells. H. Average volume of individual BRD4 foci in mock and PIC treated NLS-RL-WT cells.",
    "ncbi_link": "RL: 6041"
  },
  {
    "caption": "H, I Biotin-As pull-down assays for the transfected DNMTs (H) and DNMT3A-C520A/C524A mutation (I) in 293T cells treated with 5 μg/mL Biotin-As.",
    "ncbi_link": "DNMT3A: 1788"
  },
  {
    "caption": "E Immunoblotting of the transfected wild-type DNMT3A, C520A/C524A and C541A mutants in 293T cells upon 1 μg/mL ATO treatment for the indicated durations.",
    "ncbi_link": "DNMT3A: 1788"
  },
  {
    "caption": "B COBRA-IAP of global DNA methylation levels in MEFs upon ATO or DAC treatment at the indicated concentrations for 7 days. The signal density of unmethylated and methylated DNA were quantified by ImageJ.",
    "ncbi_link": "IAP: 16423"
  },
  {
    "caption": "C 5meC enrichment analysis of the IAP, Xist, H19 loci in MEFs upon ATO treatment at 0.3 μg/mL for 4 or 7 days as measured by MeDIP-qPCR.",
    "ncbi_link": "IAP: 16423
H19: 14955
Xist: 213742"
  },
  {
    "caption": "E COBRA-LINE-1 of global DNA methylation levels in CCRF-CEM cells upon ATO or DAC treatment in the indicated conditions. The signal density of unmethylated and methylated DNA were quantified by ImageJ.",
    "ncbi_link": "LINE-1: 54596"
  },
  {
    "caption": "F 5meC enrichment analysis of the XIST, H19 loci in CCRF-CEM cells upon ATO treatment at the indicated concentrations for 63 days as measured by MeDIP-qPCR.",
    "ncbi_link": "H19: 283120
XIST: 7503"
  },
  {
    "caption": "Schematic overview of the sample collection procedure for single-cell PCR (scPCR). Single IHC cytoplasms from acutely dissected organs of Corti of C57BL/6J (Wt) mice after hearing onset were aspirated and processed for scPCR as depicted. (B') Expression analysis of endophilins-A1-3 from individually isolated IHC cytoplasms using RT-PCR from a representative experimental run. Please note that for these experiments, negative bath control samples from before and after the isolation procedure were an essential requirement to ensure lack of contamination from cellular debris in bath solution. HPRT was used as a housekeeping gene.",
    "ncbi_link": "HPRT: 
endophilins-A1: 20404"
  },
  {
    "caption": "Ca2+-current-voltage relationships in response to 10 ms step-depolarizations. (A') The peak of Ca2+-influx was significantly reduced in endophilin 1-SKO (**p = 0.0024) and 1/3-DKO (***p < 0.0001) when compared to Wt. (Wt n = 30/ N = 20; 1-SKO n = 15/ N = 9; 1/3-DKO n = 39/ N = 20; Non-parametric K-W with post-hoc Dunn's correction).",
    "ncbi_link": "endophilin 1: 20404"
  },
  {
    "caption": "Interaction of otoferlin and endophilin-A1 detected by co-IP in HeLa cells co-expressing GFP-otoferlin and RFP-endophilin-A1. Otoferlin-GFP was immunoprecipitated (IP) by GFP-Trap beads, and blots were probed with a KO-validated anti-endophilin-A1 antibody.",
    "ncbi_link": "endophilin-A1: 
GFP: 
otoferlin: 
RFP: "
  },
  {
    "caption": "Exogenously overexpressed GFP-otoferlin was immunoprecipitated using GFP-Trap beads and incubated with purified endophilin-A1 (pA1). IP was then followed by immunoblotting with an anti-endophilin-A1 antibody.",
    "ncbi_link": "GFP: 
otoferlin: "
  },
  {
    "caption": "Increased overall number of coated structures in stimulated endophilin 1/2-DKOs. (F') Both, coated vesicles and coated pits forming at ELVs were significantly increased in 1/2-DKO after stimulation. Mann-Whitney test; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "endophilin 1: 20404"
  },
  {
    "caption": "(h) Cdk5 phosphorylates EndoB1 at Thr 145 in Cdk5+/+, but not Cdk5-/- mouse brains. Quantification of p-Thr145-EndoB1 level is shown in the right panel. Data are means ± s.e.m.; n=3. Uncropped images of blots are shown in Supplementary Fig. S8",
    "ncbi_link": "Cdk5: 12568"
  },
  {
    "caption": "(f) Overexpression of EndoB1T145A significantly reduces the starvation-induced increase in LC3-II levels (left) and the percentage of cells with RFP-LC3 puncta (right) in neurons. Data are means ± s.e.m.; n=6. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "EndoB1: 292156"
  },
  {
    "caption": "(a) Left: lipid binding of EndoB1 is inhibited by mutating the five lysine/arginine residues between amino acids 176 and 183 of EndoB1 to glutamic acid (5E mutant). Right: purified GST protein was included as a negative control. S, supernatant fraction; P, pellet fraction that contains the lipid-bound proteins.",
    "ncbi_link": "EndoB1: 292156"
  },
  {
    "caption": "(d) Overexpression of the 5E mutant of EndoB1 blocks starvation-induced autophagy in cortical neurons. Data are means ± s.e.m.; n=3.",
    "ncbi_link": "EndoB1: 292156"
  },
  {
    "caption": "(f) Starvation increases co-localization of GFP-EndoB1 (green) with Atg5 (red) in neurons. The T145A mutation of GFP-EndoB1 does not affect its co-localization with Atg5-positive entities. Arrows denote GFP-EndoB1- and Atg5- positive vesicles. The right panel shows quantified data as means ± s.e.m.; n=9. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "EndoB1: 292156"
  },
  {
    "caption": "(c) Diminished interaction between EndoB1 and UVRAG in Cdk5−/− mouse brain lysates.",
    "ncbi_link": "Cdk5: 12568"
  },
  {
    "caption": "(c) Knockdown of EndoB1 or Cdk5 inhibits MPP+-induced autophagy in cultured neurons. Data are means ± s.e.m.; n=5.",
    "ncbi_link": "Cdk5: 12568
EndoB1: 54673"
  },
  {
    "caption": "(d) Cdk5 mediates the MPP+-induced EndoB1 phosphorylation at Thr 145 and the MPP+-induced increase in the LC3-II level in neurons.",
    "ncbi_link": "Cdk5: 12568"
  },
  {
    "caption": "(e) Overexpression of EndoB1T145A attenuates MPP+-induced autophagy in neurons. Data are means ± s.e.m.; n=7.",
    "ncbi_link": "EndoB1: 54673"
  },
  {
    "caption": "(f) MPTP fails to increase LC3-II and Thr 145-phosphorylated EndoB1 levels in the midbrain of p35−/− mice. The concomitant reduction in tyrosine hydroxylase level triggered by MPTP injection is also markedly attenuated. Right panels show quantified data as means ± s.e.m.; n=3. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "p35: 12569"
  },
  {
    "caption": "(a) Upregulation of the levels of LC3-II and Thr 145-phosphorylated EndoB1 in the cerebellum and striatum of α-synucleinA53T transgenic mice. Right panels show quantified data as means ± s.e.m.; n=3.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "b) Overexpression of α-synucleinA53T mutant upregulates LC3-II level and Thr 145-phosphorylated EndoB1 in cultured neurons. Lower panel shows quantified data as means ± s.e.m.; n=3.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "(c) Knockdown of EndoB1 or Cdk5 inhibits α-synucleinA53T mutant-induced autophagy induction in neurons. Data are means ± s.e.m.; n=7.",
    "ncbi_link": "Cdk5: 12568
EndoB1: 54673
α-synuclein: 20617"
  },
  {
    "caption": "(d) Cdk5 mediates α-synucleinA53T mutant-induced Thr 145 phosphorylation of EndoB1 and the increase of LC3-II in neurons.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "(e) Overexpression of EndoB1T145A attenuates α-synucleinA53T mutant-induced autophagy in neurons. Data are means ± s.e.m.; n=7. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "EndoB1: 54673
α-synuclein: 20617"
  },
  {
    "caption": "(c) Knockdown of EndoB1 or Cdk5 expression abolishes MPP+-induced neuronal death. Data are means ± s.e.m.; n=8.",
    "ncbi_link": "Cdk5: 12568
EndoB1: 54673"
  },
  {
    "caption": "(d) Overexpression of EndoB1T145A inhibits MPP+-induced neuronal death. Data are means ± s.e.m.; n=5.",
    "ncbi_link": "EndoB1: 54673"
  },
  {
    "caption": "(e) Pretreatment with 3-MA, but not z-VAD-fmk, reduces α-synucleinA53T mutant-induced neuronal death. Data are means ± s.e.m.; n=6.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "(f) Knockdown of Atg5 expression abolishes α-synucleinA53T mutant-induced neuronal death, whereas it reduces neuronal survival in vector-transfected cells. Data are means ± s.e.m.; n=3.",
    "ncbi_link": "Atg5: 11793
α-synuclein: 20617"
  },
  {
    "caption": "(g) Knockdown of EndoB1 or Cdk5 expression abolishes α-synucleinA53T mutant-induced neuronal death. Data are means ± s.e.m.; n=4.",
    "ncbi_link": "Cdk5: 12568
EndoB1: 54673
α-synuclein: 20617"
  },
  {
    "caption": "(h) Expression of EndoB1T145A inhibits α-synucleinA53T mutant-induced neuronal death. Data are means ± s.e.m.; n=6.",
    "ncbi_link": "EndoB1: 54673
α-synuclein: 20617"
  },
  {
    "caption": "Representative flow cytometric analysis of splenocytes from mice of the indicated genotypes (pre-gated on B cells: B220+/CD19+) for surface expression of IgM and the 3-83 idiotype (54.1). Shown data are representative 11 - 35 individual mice per genotype.",
    "ncbi_link": "3-83: "
  },
  {
    "caption": "PCR fragments amplified with specific primers for Vκ and Jκ5 from genomic DNA of purified splenic B cells from Ptenf/f x 3-83ki and Ptenf/f x mb1-cre x 3-83ki mice on the respective backgrounds. Genomic tail DNA from a 3-83ki mouse and DNA from purified splenic B cells of a control (ctrl) mouse were used as controls. PCR for the splicing factor Srp20 served as a loading control. Kb and Kd indicate the respective background of the mice, (H2-Kb: +Ag).",
    "ncbi_link": "3-83: 
cre: 2777477
mb1: 14999
H2-Kb: 14972
Kb: 14972
Kd: 14972
Vκ: 546213
Jκ5: 243461
Pten: 19211
Srp20: 20383"
  },
  {
    "caption": "Splenocytes from mice of the indicated genotypes, (A) Ptenf/f, Ptenf/f x mb1-cre and Ptenf/f x mb1-cre 3-83ki mice on the respective backgrounds were analyzed by flow cytometry. B cells were pre-gated by B220 and CD19 expression and the IgM/IgD surface expression (dot plots, left) was determined. Histograms (right) show a comparison of intracellular IgD expression (Ig-δHC ic) between the splenic populations of B cells (orange, identified by B220 and CD19 expression) and non-B cells (gray). Numbers in the histograms indicate the percentages of the positive populations. Data are representative of 11 - 35 individual mice per genotype.",
    "ncbi_link": "3-83: 
cre: 2777477
mb1: 14999
Pten: 19211"
  },
  {
    "caption": "(B) Ptenf/f x MD4tg and Ptenf/f x mb1-cre x MD4tg mice in presence and absence of antigen (ML5tg), were analyzed by flow cytometry. B cells were pre-gated by B220 and CD19 expression and the IgM/IgD surface expression (dot plots, left) was determined. Histograms (right) show a comparison of intracellular IgD expression (Ig-δHC ic) between the splenic populations of B cells (orange, identified by B220 and CD19 expression) and non-B cells (gray). Numbers in the histograms indicate the percentages of the positive populations. Data are representative of 11 - 35 individual mice per genotype.",
    "ncbi_link": "MD4: 
cre: 2777477
mb1: 14999
Pten: 19211"
  },
  {
    "caption": "C | Quantification of surface IgD mean fluorescence intensity (MFI) in Ptenf/f x MD4-trangenic mice in presence (mb1-cre +/+) and absence (mb1-cre +/ki) of Pten. Single dots represent the average MFI of 4 independent measurements per mouse (n), mean ±SD. Statistical significance was calculated by using an unpaired two-tailed t-test.",
    "ncbi_link": "MD4: 
cre: 2777477
mb1: 14999
Pten: 19211"
  },
  {
    "caption": "D | Serum anti-HEL titers. Sera from MD4tg mice of the indicated genotypes were adjusted to an IgM concentration of 500 μg/ml and applied in triplicates to HEL-coated plates in dilution steps of 1 : 3, mean ±SEM. Statistical significance was calculated by using the Kruskal-Wallis test (see also Table S4). Statements of significance in the figure refer to the comparison between Ptenf/f x MD4tg (filled red squares) and Ptenf/f x MD4tg x MD5tg sera (filled orange triangles), ** p ≤ 0.01; *** p ≤ 0.001.",
    "ncbi_link": "MD4: 
MD5: 
Pten: 19211"
  },
  {
    "caption": "E | Immunohistochemistry of sections from spleens of Ptenf/f, Ptenf/f x mb1-cre, Ptenf/f x mb1-cre x 3-83ki and Ptenf/f x mb1-cre x MD4tg mice for CD169 (green), CD5 (red) and IgM (cyan) at 10x magnification. Pictures in the second row show enlarged areas indicated by the white squares, respectively. Double-arrows indicate the distance between T cell (red) and marginal zone (green). Shown pictures are representative of 2 - 3 mice per genotype",
    "ncbi_link": "3-83: 
MD4: 
cre: 2777477
mb1: 14999
Pten: 19211"
  },
  {
    "caption": "B | 3 days post transduction the surface expression of IgM/IgD (dot plots, top), IgD and CD23 (histograms, bottom) was measured by flow cytometry and compared between EV- and FoxO1-A3-transduced cells. Fluorescence minus one (FMO) stainings, lacking α-IgD or α-CD23 antibodies respectively, served as controls (ctrl). Bar diagrams below flow cytometry data display the percentages of IgD+ cells (n = 12; left) and MFI of CD23 (as relative units, RU), normalized to the MFI measured in the respective EV transduced cells; n = 12; middle). Fcer2 transcript levels were measured by qRT-PCR (right, n = 4). Mean ±SD, symbols indicate data from individual mice. Statistical significance of IgD expression was determined by applying the Wilcoxon matched-pairs signed rank test for CD23 and by applying the one sample two-tailed t-test for Fcer2 expression.",
    "ncbi_link": "FoxO1: 
Fcer2: 14128"
  },
  {
    "caption": "C | Cstf64 (n = 8), Ell2 (n = 8) and Zfp318 (n = 11) expression levels were measured at 3 days post transduction by qRT-PCR. FoxO1-A3- and EV-transduced splenic B cells were FACS-purified according to the gating strategy Mean ±SD, symbols indicate the expression in individual mice. Statistical significance was calculated by using the one-sample two-tailed t-test.",
    "ncbi_link": "FoxO1: 
Cstf64: 108062
Ell2: 192657
Zfp318: 57908"
  },
  {
    "caption": "E: IgD (n = 6), CD23 (n = 4) and Fcer2 (n = 4).",
    "ncbi_link": "Fcer2: 14128"
  },
  {
    "caption": "F: Cstf64 (n = 4), Ell2 (n = 4) and Zfp318 (n = 4).",
    "ncbi_link": "Cstf64: 108062
Ell2: 192657
Zfp318: 57908"
  },
  {
    "caption": "B | Representative flow cytometric analysis of Ramos cells reconstituted with HH10-mu IgM, HH10-mu IgD. Cells were stained with α-murine μHC-, δHC- and κLC-antibodies, respectively. EV-transduced HL-KO cells, expressing GFP only, were used as negative control (gray).",
    "ncbi_link": "GFP: 
IgD: 380797
IgM: 16019"
  },
  {
    "caption": "C | Representative flow cytometric analysis of HEL-binding in reconstituted Ramos cells after staining with fluorescently-labeled HEL. EV-transduced HL-KO cells, expressing GFP only, were used as negative control (gray).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D | Representative intracellular Ca2+ influx in HH10-mu IgM- and HH10-mu IgD-expressing cells upon stimulation with multivalent HEL (complex cHEL), monovalent (soluble sHEL) (both at a concentration of 1 μg/ml), or 10 μg/ml α-mouse κLC antibody, respectively.",
    "ncbi_link": "IgD: 380797
IgM: 16019"
  },
  {
    "caption": "E | Representative intracellular Ca2+ influx of HH10-mu IgM- (top) and HH10-mu IgD- (bottom) expressing cells upon stimulation with indicated ratios of 1 μg/ml cHEL and sHEL, and a 1 : 25 mixture of cHEL with bovine serum albumin (BSA), where 1 = 1 μg/ml.",
    "ncbi_link": "IgD: 380797
IgM: 16019"
  },
  {
    "caption": "F | Schematic overview of reconstitution of BCR-deficient Ramos (HL-KO) cells with HH10-specific human IgM (HH10-hu IgM) and IgD (HH10-hu IgD) BCR isotype. G - J | using HH10-hu IgM- and HH10-hu IgD-expressing cells instead of HH10-mu IgM- and HH10-mu IgD-expressing cells, respectively. Data shown in G to J are representative of minimum three independent experiments.",
    "ncbi_link": "BCR: 613
IgD: 3495
IgD: 380797
IgM: 3507
IgM: 16019"
  },
  {
    "caption": "| Representative intracellular Ca2+ influx measured in Thy1.2- splenocytes, derived from mice of the indicated genotypes, upon stimulation with cHEL, monovalent sHEL (both at a concentration of 1 μg/ml) or 10 μg/ml α-mouse κLC antibody, respectively. Line diagrams below the dot plots show the overlayed MFI of the Ca2+ influx kinetics displayed in the plots above.",
    "ncbi_link": "Thy1.2: 21838"
  },
  {
    "caption": "B | Analysis of GC B cells in splenic B220+ B cells from wild type (WT, top) and IgD-/- (bottom) animals after 4, 7 and 10 days (left to right) post immunization. Percentages of follicular B cells (Fo.B; CD38+/CD95-) and GC B cells (CD38-/CD95+) are depicted in the plots. GC B cells (CD38-/CD95+) were further analyzed for GL-7 expression, compared to Fo.B cells and quantified.",
    "ncbi_link": "IgD: 380797"
  },
  {
    "caption": "C | Quantification of Fo.B cells (top, percentages) and CD38-/CD95+/GL-7+ GC cells (percentages and absolute numbers, bottom panels) in WT (black) and IgD-/- (green) animals after 4, 7, 10 and 14 days post immunization, mean ±SD (numbers of animals indicated in the top plot). Statistical significance was analyzed by a two-tailed unpaired t-test.",
    "ncbi_link": "IgD: 380797"
  },
  {
    "caption": "D | Analysis of GC in spleen sections from WT and IgD-/- animals after 4, 7 and 10 days post immunization. Representative images of 2 x 2 mm sections stained with DAPI (nuclei) and peanut agglutinin (PNA) are shown for the indicated time points. Scale bar represents 500 μm. Dashed white or yellow lines mark distinct GC foci in the merged images. E | Representative 800 x 800 μm regions of areas marked by yellow dashed lines within the images of D are shown as enlarged single GCs. As no distinct GC foci were observed in IgD-/- samples from days 4 and 7, an identical 800 x 800 μm region is shown in each case. F | Quantification of number of GCs per mm2 area of spleen sections from WT (black) and IgD-/- (green) animals after 4, 7 and 10 days post immunization. Data represent mean ±SD of two sections (from 3 animals per group and time point) and were analyzed by two-tailed unpaired t-test. ",
    "ncbi_link": "IgD: 380797"
  },
  {
    "caption": "G | Total serum α-TNP IgG. Sera from PBS- or TNP-Ova-immunized WT (left) and IgD-/- (middle) mice, collected at day 7 following immunization, were adjusted to an IgG concentration of 1 μg/ml and applied in duplicates and dilution steps of 1 : 3 to TNP-coated plates, respectively, mean ±SEM. Right: Overlay of α-TNP IgG titers from TNP-Ova-immunized WT and IgD-/- mice. Statistical significance was calculated by using the Mann-Whitney-U test (see also Table S7), n. s. = not significant, * p ≤ 0.05, ** p ≤ 0.01.",
    "ncbi_link": "IgD: 380797"
  },
  {
    "caption": " Pregnant dams were injected with 4-OHT at days E10.5 and E11.5 for analysis at day E12.5 or E10.5, E11.5, and E12.5 of development for later times of analysis Developmental loss of VE-cadherin leads to severe edema. Fetuses of the genotypes listed in the top row were analyzed at the developmental stages in the first column. Numbers in brackets denote embryos with signs of edema. Last column lists the percentage of viable fetuses in the VE-cadherin deleted cohort Fetuses were explanted at day E14.5. Arrowheads indicate prominent edema along the back. The images are representative for 42 (Cdh5lox/lox) and 25 (Cdh5lox/lox; Prox1-CreERT2) analyzed animals",
    "ncbi_link": "Cdh5: 12562
VE-cadherin: 12562
Cre: 2777477
ERT2: 2099
Prox1: 19130"
  },
  {
    "caption": " Pregnant dams were injected with 4-OHT at days E10.5 and E11.5 for analysis at day E12.5 or E10.5, E11.5, and E12.5 of development for later times of analysis Skin wholemount preparations stained for PROX1, PECAM1 and VEGFR-3. Maximum intensity projections (MIPs) of tiled confocal stacks (Cdh5lox/lox 2075µm x 2075µm, z=50µm; Cdh5lox/lox; Prox1-CreERT2 3765µm x 3765 µm, z=61µm). Scale bars = 100 μm. The data are representative for 6 (Cdh5lox/lox) and 6 (Cdh5lox/lox; Prox1-CreERT2) analyzed animals from 3 litters",
    "ncbi_link": "Cdh5: 12562
Cre: 2777477
ERT2: 2099
Prox1: 19130"
  },
  {
    "caption": " Pregnant dams were injected with 4-OHT at days E10.5 and E11.5 for analysis at day E12.5 or E10.5, E11.5, and E12.5 of development for later times of analysis Enumeration of the PROX1-expressing (PROX1+) nuclei in three different VE-cadherin deleted wholemount preparations analogous to Fig. 1B. Nuclei were counted in a MIP corresponding to an area of 1.5 mm2 and normalized to the number of nuclei in Cdh5lox/lox control preparations The area covered by lymphatic vessels was determined in the samples evaluated in (D) and is depicted as relative area compared to Cdh5lox/lox controls. The calculations and measurements were obtained from three animals and three confocal stacks per biological group. PROX1-positive nuclei were counted using the particle analysis tool of Fiji",
    "ncbi_link": "Cdh5: 12562
VE-cadherin: 12562"
  },
  {
    "caption": " Deletion of VE-cadherin in lymphatic endothelial cells of newborn pups was induced by two optimal doses of 4-OHT at days P2 and P4. For analysis 6 weeks later ear punches were subjected to wholemount immunostaining of the dermal vasculature. A-H (A, B, E, F) Overview MIPs of ear skin wholemount preparations immunostained for the indicated antigens. VEC, VE-cadherin; PRX, PROX1. (C, D, G, H) Magnified views of the areas in the red boxes in (A, E). Areas delimited by the stippled yellow boxes in (C) and (G) are enlarged in the insets (yellow solid boxes). Yellow arrows indicate widened lumen, yellow arrowheads denote oak leaf-shaped LECs with discontinuous junctions. Scale bars in (A and E) correspond to 100 μm and in (C and G) to 50 µm. The data are representative for 6 (Cdh5lox/lox) and 5 (Cdh5lox/lox; Prox1-CreERT2) analyzed animals from 2 litters ",
    "ncbi_link": "Cdh5: 12562
VE-cadherin: 12562
Cre: 2777477
ERT2: 2099
Prox1: 19130"
  },
  {
    "caption": " A-L VE-cadherin deletion was initiated either in newborn pups (A, B, E, F) by two applications of 4-OHT at days P2 and P4 or in mice at 11 weeks (C, G) and 42 weeks (D, H) of age (three applications of Tamoxifen at 2 day intervals via oral gavage). Ear skins were prepared 6 weeks (A, B, E, F) or 5 weeks (C, D, G, H) after induction and immunostained for the indicated proteins. Shown are MIPs of confocal tile scans (approx. 750 µm x 750 µm) covering 40 µm in depth. White arrows in (F) highlight distorted and partially fragmented lymphatic vessels and white arrowheads denote aberrantly pointed vessels (F). (I-L) Lymphatic valves in the dermis of the ear were maintained for 5 weeks despite deletion of VE-cadherin at 11 weeks of age (yellow arrows in K, L). PEC1, PECAM1; PRX1, PROX1;VR3, VEGFR-3. Scale bars correspond to 100 μm. The data represent wholemount stainings from 6 (A, E), 5 (B, F), 6 (C, G, K, L), 3 (D, H) and 6 (I, J) analyzed animals ",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "  Fig. 4: VE-cadherin is indispensable for the maintenance of mesenteric lymphatic vessels at all ages. A-F Deletion of VE-cadherin was induced in mice at various age (4 weeks (A), neonate (B), 6 month (C, D, E) or 1 year (F)) by either two applications of 4-OHT at days P2 and P4 (neonates) or three applications of Tamoxifen at 2 day intervals via oral gavage (all other ages). The mesentery was prepared as indicated 4, 6, 8 or 11 weeks later and the wholemount preparations were immunostained for the proteins specified in color (left). (B) Inset in top panel shows a magnification of the area outlined by the white dashed line (for further magnification see expanded view Fig. 1A and B). Arrows indicate the previous position of lymphatic valves; white arrowheads indicate PECAM1+ capillaries supplying the intestinal fat tissue lining the vessels (magnified in expanded view Fig. 1C); yellow arrowheads denote island of LECs that display intracellular VEGFR-3 staining. (C) Arrows denote LECs that have converted from growth as tubes to sheets; white arrowheads, thinning of lymphatic vessels; yellow arrowheads, aberrant sprouting of LECs. The area outlined by a white box is depicted magnified in (D) and provides details on LECs growing as a sheet of cells. (E) Formation of ectopic sprouts from the valve area of degenerating lymphatic vessels. (F) Fully deteriorated lymphatic vessel with emanating sprouts that initiate sheet-like growth. PEC1, PECAM1; PRX1, PROX1; VR3, VEGFR-3. Scale bars = 100 μm. The data represent n=5 (A), n=5 (B), n=3 (C-E) and n=6 (F) animals.  ",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "  Fig. 5: Deletion of VE-cadherin results in fragmentation and distension of the intestinal lacteals. A-E Deletion of VE-cadherin was induced in mice at various ages (neonatal (C), 16 weeks (D) or 1 year (E)) by either two applications of 4-OHT at days P2 and P4 (neonates) or three applications of Tamoxifen at 2 day intervals via oral gavage (all other ages).Control mice of the same age were subjected to an identical regimen (A, B). Intestinal wholemount preparations of the jejunum and ileum were generated 5 - 8 weeks after Tamoxifen induction and immunostained for the indicated proteins, scale bars = 100 μm. The data represent wholemount stainings from 3 (D), 5 (B,E) and 6 (A, C) animals analyzed for each genotype.  ",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "Deletion of VE-cadherin was induced in adult mice (13 weeks) and EdU incorporation into PROX1-positive cell nuclei was determined 6 weeks after Tamoxifen administration. Shown are mesenteric wholemount stainings prepared from control (A, B; n=3) or VE-cadherin-deleted mice (C, D; n=3). (B) and (D) show a magnification of the area outlined by the white dashed line in (A) and (C). Antigens shown in addition to the EdU incorporation are depicted in colour on the left side of the first panel. PEC, PECAM1; PRX1, PROX1. Scale bars = 100 µm Enumeration of EdU-positive LECs. The measurements were obtained from three animals and nine confocal stacks per biological group. PROX1-positive nuclei were counted using the particle analysis tool of Fiji. Co-localization of PROX1 and EdU was determined manually in each confocal plane, using the cell counting tool of Fiji. The data represent mean ± SD. **** p ≤ 0.0001. Two-tailed unpaired Student's t test",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "Aberrantly enhanced VEGFR-3 phosphorylation in VE-cadherin-deficient mesenteric LECs of six weeks old mice that had received 4-OHT injections at P2 and P4. Shown are wholemount immunostainings for the antigens shown on the left in color. pVR3, pVEGFR-3, PRX1, PROX1; PEC1, PECAM1. (G) and (I) show a magnification of the area outlined by the white dashed box in (F) and (H). Scale bars = 50 μm. The data are representative for 6 (Cdh5lox/lox) and 5 (Cdh5lox/lox; Prox1-CreERT2) analyzed animals from 2 litters",
    "ncbi_link": "Cdh5: 12562
VE-cadherin: 12562
Cre: 2777477
ERT2: 2099
Prox1: 19130"
  },
  {
    "caption": "Dermal, mesenteric and intestinal tissue pieces of 15 week old control (Cdh5lox/lox) mice were dissociated and total RNA was extracted immediately. For reverse transcription 2.0 µg of total RNA was used for each tissue type. Expression of lymphangiogenic factors VEGF-C and VEGF-D was determined by quantitative real-time (qRT)-PCR using specific TaqMan probes. Samples were measured in triplicate and diagrams are representative for 3 independent experiments. Relative expression (ΔΔCt) of target genes was normalized to the control transcript UBC",
    "ncbi_link": "Cdh5: 12562
UBC: 22190
VEGF-C: 22341
VEGF-D: 14205"
  },
  {
    "caption": "Expression of the transcriptional co-activators YAP and TAZ was analyzed in mesenteric wholemount preparations 8 weeks after induction of VE-Cadherin deletion at 1 year of age by three doses of Tamoxifen. Respective antigens depicted are indicated on the top of the panels in colour. The highly related molecules YAP and TAZ were both recognized by the antibody used and are therefore collectively abbreviated Y/T. Scale bars = 100 μm",
    "ncbi_link": "VE-Cadherin: 12562"
  },
  {
    "caption": "  Fig. 7: Loss of VE-cadherin from lymphatic endothelial cells results in increased circumferential actin and a reduced number of focal adhesions. A, B Primary dermal LECs were isolated as described in appendix Fig. S8 A. PdLECs were used for up to four passages and control and VE-cadherin-deleted pdLECs had been cultured for the same number of passages. Cells were seeded at a density of 2.5 x 104 cells on gelatine-coated 15mm glass coverslips and co-stained after 3 days of culture for the actin cytoskeleton (Phalloidin) and either Vinculin (A) or FAK (B) for the visualization of focal adhesions. PROX1 staining in (A) identifies LECs, nuclei in (B) were counterstained with Hoechst. Scale bars correspond to 50 µm. (C, D) Bar diagrams show the number of focal adhesions/cell, which were enumerated using Image J from the Vinculin and FAK stainings shown in (A and B). Data are mean values + S.E.M. derived from three cell lines and 9 viewfields of 256 µm x 256 µm per biological group. *** p ≤ 0.001. Two-tailed unpaired Student's t test.  ",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "  Fig. 8: Enhanced collective cell migration in VE-cadherin-deficient lymphatic endothelial cells. (A) Collective cell migration of VE-cadherin-deficient and control LECs was assessed in wound scratch assays. LECs were grown up to four passages and seeded at a density of 5x104 cells on fibronectin-coated 8 well µ-chamber slides (growth area 0.22 cm2); scale bar 500 µm (B) The area of the zone denuded from cells is depicted in the curve diagram showing mean values ± SD of three individual experiments conducted in quadruplets. * p ≤ 0.01. Two-tailed unpaired Student's t test. Expanded View Figures - Legends  ",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "Micronuclei (indicated by arrow head) in GFP-NLS- or GFP-hcGAS expressing HEK293 cells before (0 h) or 24 h after γ-irradiation (IR; 10 Gy). Scale bar: 10 μm (A).",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "Micronuclei (indicated by arrow head) in GFP-NLS- or GFP-hcGAS expressing HEK293 cells before (0 h) or 24 h after γ-irradiation (IR; 10 Gy). The average MNs/cell. Graphs show Mean ± SEM (n=3 independent experiments) representing six different microscopic fields with over 200 cells.",
    "ncbi_link": "GFP: 
cGAS: 214763"
  },
  {
    "caption": "IFNB1 response in HEK293 cells stimulated with transfected plasmid DNA. Mean ± SEM of n=3 independent experiments.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "Micronuclei (indicated by arrow head) and cGAS staining in WT and cGAS-/- BMDMos exposed to γ-irradiation (10 Gy). Scale bar: 10 μm.",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "Cell death in WT and cGAS-/- BMDMos that were first synchronized at G2/M, then γ-irradiated (10 Gy) followed by release and analysis at indicated time points. Mean ±SD, x biological triplicates (n=3) per treatment group are shown.",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "BMDMos from cGAS-/- mice exhibit enhanced DNA repair efficiency than those from WT and Sting-/- mice. (A) Representative comet tails of WT, cGAS-/- and Sting-/-BMDMos exposed to γ-irradiation (IR: 10 Gy) on ice then incubated at 37 ̊C for indicated duration. (B) Corresponding quantification of the comet tail moments from 20 different fields with n > 200 comets of 3 independent experiments.",
    "ncbi_link": "cGAS: 214763
Sting: 72512"
  },
  {
    "caption": "cGAS promotes micronuclei generation in BMDMos independently of STING. Confocal microscopic visualization of micronuclei (indicated by arrow head) and cGAS staining in WT, cGAS-/- and Sting-/- BMDMos exposed to γ-irradiation (10Gy). Scale bar: 10 μm.",
    "ncbi_link": "cGAS: 214763
Sting: 72512"
  },
  {
    "caption": "γ-irradiation-induced cell death in WT, cGAS-/- BMDMos",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "γ-irradiation-induced cell death in Sting-/- and cGAS-/- Sting-/- BMDMos (F).",
    "ncbi_link": "cGAS: 214763
Sting: 72512"
  },
  {
    "caption": "Bone marrow cells in WT (n=3) and cGAS-/- (n=3) mice 10 hours post γ-irradiation.",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "Bone marrow cells in Sting-/- (n=3) and cGAS-/- Sting-/- (n=3) mice 10 hours post γ-irradiation.",
    "ncbi_link": "cGAS: 214763
Sting: 72512"
  },
  {
    "caption": "Obtained results showing enhanced HR efficiency upon knockdown of endogenous cGAS in U2OS cells. Immunoblot inserts in depict knockdown efficiency of cGAS and Histone H1.2.",
    "ncbi_link": "cGAS: 115004
Histone H1.2: 3006"
  },
  {
    "caption": "Obtained results showing enhanced HR efficiency upon knockdown of endogenous cGAS in U2OS cells. Immunoblot inserts in depict knockdown efficiency of cGAS and Histone H1.2.",
    "ncbi_link": "cGAS: 115004
Histone H1.2: 3006"
  },
  {
    "caption": "Results showing the effect of hcGAS, hcGAS△cGAMP, hcGAS△DNA or hcGAS△Oligo on HR in HEK293 cells. Corresponding immunoblot inserts depict cGAS expression.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "Results showing the effect of hcGAS, hcGAS△cGAMP, hcGAS△DNA or hcGAS△Oligo on NHEJ in HEK293 cells. Corresponding immunoblot inserts depict cGAS expression.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "cGAS is not recruited to DSB sites: Confocal microscopic images of GFP-NLS- or GFP-hcGAS-expressing U2OS-DSB reporter cells incubated (or not) with Shield-1 and 4-OHT to induce the expression and translocation of mCherry-LacI-FokI (red) to specific DSB sites. Scale bar: 10μm. The arrowheads indicate DSB sites.",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "cGAS does not colocalize with γ-H2AX at DSB sites: GFP-NLS- or GFP-hcGAS- expressing HEK293 cells exposed (or not) to γ-irradiation (IR: 10 Gy) then stained for γ-H2AX. Scale bar: 10 μm.",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "cGAS co-isolates with DNA repair proteins because of bound chromatin bridges. Nuclease digestion abrogates the co-isolation of cGAS and DNA repair proteins: Lysates of control (-IR) and γ-irradiated (+IR, 10 Gy, 30 min) GFP-hcGAS expressing HEK293 cells were treated (or not) with Benzonase before cGAS immunoprecipitation and analysis for indicated proteins. Agarose gel analysis of DNA in corresponding cell lysates in (E).",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "cGAS co-isolates with DNA repair proteins because of bound chromatin bridges. Co-isolation of cGAS and DNA repair proteins depends on its binding to DNA: cGAS pulldowns along with lysate inputs of control and γ-irradiated HEK293 cells expressing GFP-hcGAS or GFP-hcGASΔDNA probed for indicated proteins.",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "Confocal images of γ-irradiated GFP-NLS-, GFP-hcGAS-expressing HEK293 cells stained for RAD51 (red) with or without γ-irradiation. Scale bar: 10 μm.",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "Effect of indicated hcGAS variants on D-loop formation when pre-incubated with dsDNA. Percentage of D-loop formed in each reaction (left) graphed as the average of triplicates± SD.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "DR-GFP assay showing that hcGASΔDNA-Y215E is impaired in HR inhibition.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "hcGASΔDNA-Y215E but not hcGASΔcGAMP has a decreased affinity to dsDNA24.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "hcGASΔDNA-Y215E and hcGASΔcGAMP are defective in synthase activity.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "Negative-stain electron micrographs showing that hcGAScat-ΔDNA-Y215E is defective in inducing cGAS-dsDNA complexes. Scale bar: 100 nm.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "Effect of indicated hcGAS variants on D-loop formation.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "C. Representative images of DIV3 DRG neurons  nucleofected with a non-targeting siRNA (NT siRNA) or a siRNA against DLK  (DLK  siRNA), and stained for endogenous DLK  and β3-tubulin (TUBB3). On the right, quantification of the DLK  mean intensity in neurons  expressing control NT or DLK  siRNAs (n = 25 neurons/condition; Unpaired t test). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. Scale bar represents 10 μm in (C) 2 μm in zooms in (C).",
    "ncbi_link": "DLK: 26404"
  },
  {
    "caption": "I-J. Representative  Western blots  of p-cJun and GAPDH  (I), and quantification of relative c-Jun phosphorylation  levels (J) from DIV6 cultured embryonic DRG neurons  overexpressing GFP  or NtermDLK-GFP, and subjected to NGF  withdrawal for 3h (n = 7-8 biological replicates; series of unpaired t tests /Mann-Whitney U tests followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "L. Representative images of HeLa  cells expressing the different HA-tagged wild-type (WT) and palmitoyl-mutant (CS) DLK  constructs (DLK-WT-ER, DLK-CS-ER, DLK-WT-CAAX, DLK-CS-CAAX, DLK-WT-MTS, DLK-CS-MTS), and stained  with markers of the  endoplasmic reticulum (KDEL), plasma membrane  (CellMask) and mitochondria  (cytochrome C). Data information: Scale bar represents 5 μm in (L)",
    "ncbi_link": "HA: 
DLK: 26404"
  },
  {
    "caption": "M-N. Representative Western blots of DLK, p-cJun and GAPDH  (M) and quantification of relative  c-Jun phosphorylation  levels (N) from HeLa  cells transfected with HA  alone (HA) and the different HA-tagged wild-type (WT) and palmitoyl-mutant (CS) DLK  constructs (DLK-WT-ER, DLK-CS-ER, DLK-WT-CAAX, DLK-CS-CAAX, DLK-WT-MTS, DLK-CS-MTS) (n = 7-8 biological replicates; series of unpaired t tests /Mann-Whitney U tests with DLK-WT or DLK-CS followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "HA: 
DLK: 26404"
  },
  {
    "caption": "Representative Western blots  of GFP, p-cJun and GAPDH  (B) from HeLa  cells non transfected (NT) or transfected with GFP  alone (GFP), GFP-tagged DLK  wild-type (DLK-WT-GFP), kinase dead mutant (DLK-KD-GFP), leucine zipper domain mutant (DLK-LZ-GFP) and a palmitoyl-site mutant (DLK-CS-GFP)",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "quantification of relative c-Jun phosphorylation  levels (C) from HeLa  cells non transfected (NT) or transfected with GFP  alone (GFP), GFP-tagged DLK  wild-type (DLK-WT-GFP), kinase dead mutant (DLK-KD-GFP), leucine zipper domain mutant (DLK-LZ-GFP) and a palmitoyl-site mutant (DLK-CS-GFP) (n = 4-7 biological replicates; series of unpaired t tests /Mann-Whitney U tests with DLK-WT-GFP  followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 and ***p < 0.001.",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "D. Representative images and zooms of HeLa cells expressing GFP  alone or the different GFP-tagged DLK  mutants. Data information: Scale bar represents 100 μm in (D) zooms in (D).",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "E-F. Representative  Western blots of GFP, α-tubulin and Na+/K+-ATPase  from cytosolic  and membrane  fractions (E) and quantification of the percentage of DLK localized  in the membrane  and cytosolic  fraction (F) from HeLa  cells expressing GFP  alone or the different GFP-tagged DLK  mutants (n = 4-5 biological replicates; series of unpaired t tests /Mann-Whitney U tests with DLK-WT-GFP  followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 and ***p < 0.001.",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "G-I. Representative stills (G), representative kymographs (H) and quantification of the number of GFP-positive particles (I) from time-lapse recordings of the different GFP-tagged DLK  mutants in DIV6 cultured embryonic DRG neurons (n = 31-65 neurons/condition; series of Mann-Whitney U tests with DLK-WT-GFP  followed by a Holm-Sidak correction). Data information: Arrowheads point to individual DLK-GFP  positive structures in G All graphs represent mean ± SEM. *p < 0.05 and ***p < 0.001. Scale bar represents 10 μm in (G) , 5 μm in (H)",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "C. Representative images of HeLa  cells expressing HA   alone and the different HA-tagged DLK  constructs: a wild-type form of DLK  (DLK-WT-HA) and the palmitoyl-mutant DLK  (DLK-CS-HA). Data information: Scale bar represents 20 μm in (C)",
    "ncbi_link": "HA: 
DLK: 26404"
  },
  {
    "caption": "D. Western blot analysis from total lysate (Input) and immunoprecipitates  (IP) of HA-tag protein immunoprecipitations  in HeLa  cells overexpressing HA  alone and the different HA-tagged DLK  constructs, DLK-WT-HA  and DLK-CS-HA  in the absence of any detergent.",
    "ncbi_link": "HA: 
DLK: 26404"
  },
  {
    "caption": "E-F. Lipidomic analysis of the immunoprecipitates  obtained from the HA-tagged protein immunoprecipitations  from extracts of HeLa  cells overexpressing HA  alone, DLK-WT-HA  and DLK-CS-HA. Quantification of lipid  classes (E) and sphingomyelin  fatty acid species (F) measured in the immunoprecipitates  (n = 3-4 independent experiments; series of unpaired t tests /Mann-Whitney U tests followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. CE, cholesteryl ester; CER, ceramide; DAG, diacylglycerol; DCER, dihydroceramides; HCER, hexosylceramides, LCER, lactosylceramides; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; PC, phosphatidylcholine; PE, phosphatidylethanolamine; SM, sphingomyelin; TAG, triacylglycerol.",
    "ncbi_link": "HA: 
DLK: 26404"
  },
  {
    "caption": "Representative stills (J) from  time-lapse recordings from 6DIV cultured embryonic DRG neurons  overexpressing GFP-tagged DLK  and treated with D609  for 3h (n = 29-46 neurons  Arrowheads in J point to individual DLK-GFP  positive structures. Data information: Scale bar represents 10 μm in (J)",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "kymographs  and quantification of the number of DLK-GFP  positive particles (K) from  time-lapse recordings from 6DIV cultured embryonic DRG neurons  overexpressing GFP-tagged DLK  and treated with D609  for 3h (n = 29-46 neurons; Mann-Whitney U test). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. Scale bar represents , 5 μm in (K)",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "Representative stills (C), kymographs (D) and quantification of the orientation (E) of DLK-GFP  positive particles from time-lapse recordings of DIV6 DRG neurons  overexpressing GFP-tagged DLK  and treated with dynasore  (DYN) or brefeldin A (BFA) for 3h (n = 34-101 neurons, Chi-square test in E Arrowheads in C point to individual DLK-GFP  positive structures. Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. Scale bar represents 10 μm in (C) and , 5 μm in (D)",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "quantification of number of DLK-GFP  positive particles (F) from  time-lapse recordings of DIV6 DRG neurons  overexpressing GFP-tagged DLK  and treated with dynasore  (DYN) or  brefeldin A (BFA) for 3h (n = 34-101 neurons, series of Mann-Whitney tests with control followed by a Holm-Sidak correction in F). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001.",
    "ncbi_link": "GFP: 
DLK: 26404"
  },
  {
    "caption": "C. Representative images of DRG neurons  expressing GFP, Dnm-1-WT-HA  or Dnm1-DN-HA  form, cultured in the absence of NGF  for 8h, and stained  with antibodies against cCasp3  (magenta) and HA  tag (green). On the right, quantification of the ratio of cCasp3 positive cells over GFP  or HA  positive cells (n = 10-15 images from 3 independent cultures, series of unpaired t-test/Mann-Whitney U tests with control NGF  withdrawal followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. Scale bar represents 20 μm in (C)",
    "ncbi_link": "GFP: 
HA: 
Dnm-1: 13429
Dnm1: 13429"
  },
  {
    "caption": "F. Representative images of axons  from cultured embryonic DRG neurons  expressing GFP, Dnm-1-WT-HA  or Dnm1-DN-HA  form and deprived of NGF   for 24h, and visualized with an antibody against neurofilament heavy chain (NFH). On the right, quantification of fragmented axons  using the  degeneration index in (n = 8-13 images from 3 independent cultures, series of unpaired t-test tests with control NGF   withdrawal followed by a Holm-Sidak correction). Data information: All graphs represent mean ± SEM. *p < 0.05 **p < 0.01 and ***p < 0.001. Scale bar represents 40 μm in (F)",
    "ncbi_link": "GFP: 
HA: 
Dnm-1: 13429
Dnm1: 13429"
  },
  {
    "caption": "(A) qRT-PCR analysis for Islr, Chd1 and Vim in total intestinal tissues, intestinal epithelium and lamina propria. n = 4.",
    "ncbi_link": "Chd1: 12648
Islr: 26968
Vim: 22352"
  },
  {
    "caption": "(C) qRT-PCR analysis for Islr in CD45+, CD45-Epcam+, CD45-Epcam-CD90+ and CD45-Epcam-CD90- cells sorted from intestinal tissues. n = 3 technical replicates.",
    "ncbi_link": "Islr: 26968"
  },
  {
    "caption": "(D) In situ hybridization for Islr with RNAscope probe in intestine and colon from 8-week-old mice, showing that Islr is primarily expressed in stromal cells. Negative and positive controls were shown in Appendix Figure S1A. Scale bar: 25 μm.",
    "ncbi_link": "Islr: 26968"
  },
  {
    "caption": "(E) In situ hybridization for ISLR with RNAscope probe in human mucosa, inflamed mucosa from CD and UC patients. Scale bar: 25 μm.",
    "ncbi_link": "ISLR: 3671"
  },
  {
    "caption": "(F) qRT-PCR analysis showing the dynamic changes of Islr in colonic tissues from mice upon DSS treatment and after DSS removal. n = 4 at each time points.",
    "ncbi_link": "Islr: 26968"
  },
  {
    "caption": "(G) In situ hybridization for Islr with RNAscope probe in mouse colons without or with 3-day or 5-day DSS treatments. Scale bar: 50 μm.",
    "ncbi_link": "Islr: 26968"
  },
  {
    "caption": "(H) The cancer genome atlas (TCGA) RNA-seq analysis showing that ISLR is upregulated in human rectal adenocarcinoma relative to normal rectal tissues. The horizontal lines between the box limits represent the median, the box limits indicate the interquartile ranges and the whiskers indicate limit superior and limit inferior respectively. n = 65.",
    "ncbi_link": "ISLR: 3671"
  },
  {
    "caption": "(J) ISLR level increased with nodal metastasis in colorectal cancer patients. N0, no regional lymph node metastasis; N1, metastases in 1 to 3 axillary lymph nodes; N2, metastases in 4 to 9 axillary lymph nodes; N3, metastases in 10 or more axillary lymph nodes. The solid horizontal lines represent the median, the box limits indicate the interquartile ranges and the whiskers indicate limit superior and limit inferior respectively.",
    "ncbi_link": "ISLR: 26968"
  },
  {
    "caption": "(K In situ hybridization for ISLR/Islr with RNAscope probes in normal human colon, human malignant adenocarcinoma, metastatic adenocarcinoma (K), t indicating tumor; a indicating adjacent tissues of tumor. Scale bar: 50 μm.",
    "ncbi_link": "ISLR: 26968
Islr: 26968"
  },
  {
    "caption": "L) In situ hybridization for ISLR/Islr with RNAscope probes in mouse colon tumors from AOM-DSS model (L). t indicating tumor; a indicating adjacent tissues of tumor. Scale bar: 50 μm.",
    "ncbi_link": "ISLR: 26968
Islr: 26968"
  },
  {
    "caption": "(B) qRT-PCR analysis for Ets1 in colonic epithelium and lamina propria. n = 3.",
    "ncbi_link": "Ets1: 23871"
  },
  {
    "caption": "(D) qRT-PCR for Ets1 in colons with or without 5-day DSS treatment. n = 4.",
    "ncbi_link": "Ets1: 23871"
  },
  {
    "caption": "(F) Pearson correlation analysis on ETS1 and ISLR in colorectal adenocarcinoma TCGA RNA-seq (P < 0.001; R = 0.68).",
    "ncbi_link": "ETS1: 2113
ISLR: 3671"
  },
  {
    "caption": "(G) Western blotting for ISLR and HA in lysates of UC-MSCs transfected with pCMV5-HA or pCMV5-ETS1. α-Tubulin was used as a loading control.",
    "ncbi_link": "HA: 
ETS1: 23871"
  },
  {
    "caption": "(H) Luciferase activity in lysates of UC-MSCs transfected with luciferase reporter plasmids of pGL3-basic empty vector (basic), wild type ISLR promoter or mutant promoter with mutation of ETS1 binding sites under normal and ETS1 overexpression conditions. n = 3.",
    "ncbi_link": "luciferase: 
ETS1: 23871
ISLR: 26968"
  },
  {
    "caption": "(I) Chromatin immunoprecipitation assay was carried out on UC-MSCs cells using antibodies against ETS1 and Histone H3. The antibody against Histone H3 was used as a positive control. IgG was used as a negative control. The enrichment of ETS1 binding to ISLR promoter was quantified using qPCR. n = 3 technical replicates.",
    "ncbi_link": "ETS1: 23871
ISLR: 26968"
  },
  {
    "caption": "(J) Chromatin immunoprecipitation assay was carried out on primary intestinal stromal cells isolated from WT mice without DSS treatment or WT mice after 5-day DSS treatment using antibodies against ETS1 and Histone H3. The antibody against Histone H3 was used as a positive control. IgG was used as a negative control. The enrichment of Ets1 binding to Islr promoter was quantified using qPCR. n = 3 technical replicates.",
    "ncbi_link": "Islr: 26968"
  },
  {
    "caption": "(H) The growth curve of HCT116 colorectal cancer cells cultured in the supernatant from WT or cKO IMCs, concomitantly transfected with PCDH empty vector or PCDH-YAP1-5SA vector. n = 4 technical replicates.",
    "ncbi_link": "YAP1: 10413"
  },
  {
    "caption": "(I) Pearson correlation analysis of ISLR and CTGF (P < 0.001; R = 0.69), ISLR and FSTL1 (P < 0.001; R = 0.81), as well as ISLR and CYR61 (P < 0.001; R = 0.65) in human colorectal cancer based on TCGA RNA-seq database.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
FSTL1: 11167
ISLR: 3671"
  },
  {
    "caption": "(A) Schematics of culture epithelial cells with supernatant from HEK293FT cells transfected with pcDNA3.1 empty vector or pcDNA3.1-hISLR-HA plasmids. Western blotting for HA in the supernatant from HEK293FT cells transfected with the indicated plasmids.",
    "ncbi_link": "hISLR: 3671"
  },
  {
    "caption": "(E) Western blotting for HA and ISLR in the supernatant from NCM460 colonic epithelial cells with pcDNA3.1 empty vector or pcDNA3.1-hISLR-HA plasmids. Western blotting for pMST1/2, MST1, pMOB1 and MOB1, pYAP1 and YAP1 in lysates from NCM460 CRC cells cultured in the supernatants with or without hISLR-HA. β-actin was used as a loading control.",
    "ncbi_link": "HA: 
hISLR: 3671"
  },
  {
    "caption": "(H) qRT-PCR for CTGF and CYR61 in HEK293FT cells cultured in the supernatant with or without hISLR-HA. n=3.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490"
  },
  {
    "caption": "(A) Western blotting for Islr in the supernatant from primary cultured intestinal epithelial cells (IECs) transfected with pcDNA3.1 or pcDNA3.1-mIslr-HA plasmids, and western blotting for pMst1/2, Mst1, pMob1 and Mob1, pYap1 and Yap1 in lysates from primary IECs cultured in the supernatants with or without mIslr-HA. β-actin was used as a loading control.",
    "ncbi_link": "HA: 
mIslr: 26968"
  },
  {
    "caption": "(C) qRT-PCR for Ctgf, Cry61 and Fstl1 in primary intestinal epithelial cells cultured in the supernatant with or without mIslr for 24 hours. n=4.",
    "ncbi_link": "Cry61: 16007
Ctgf: 14219
Fstl1: 14314"
  },
  {
    "caption": "(D) Activity of TEAD-Luciferase reporter in primary intestinal epithelial cells upon mIslr, Yap1 or mIslr and Yap1. n=4.",
    "ncbi_link": "Luciferase: 
TEAD: 7004"
  },
  {
    "caption": "(F) qRT-PCR for Ctgf and Cry61 in primary intestinal epithelial cells 48 hours after treatments of mIslr or/and Yap1 siRNA (siYap1). n=4.",
    "ncbi_link": "Cry61: 16007
Ctgf: 14219
Yap1: 22601"
  },
  {
    "caption": "(I) qRT-PCR for Ctgf, Cry61 and Fstl1 in primary intestinal organoids 24 hours after the treatments. n=3.",
    "ncbi_link": "Cry61: 16007
Ctgf: 14219
Fstl1: 14314"
  },
  {
    "caption": "(A) Analysis of the single-cell transcriptomics dataset for the mouse visual cortex (Tasic et al, 2016) revealed that the expression of the metabolism-associated gene Cox6a2 is highly restricted to PV+ interneurons. Cox6a2 is expressed in all subtypes of PV+ interneurons (marked in blue color) but rarely detected in other neuronal subtypes from the mouse visual cortex. Cox6a1, which encodes the other protein isoform of COX6A, is expressed in all subtypes.",
    "ncbi_link": "Cox6a1: 12861
Cox6a2: 12862"
  },
  {
    "caption": "(B RT-PCR showing expression of Cox6a2 in the brain and heart.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(A) Images showing absence of COX6A2 immunoreactivity in the cortex of Cox6a2-/- mice.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(B,C) Parvalbumin immunoreactivity in PV+ interneurons was significantly decreased in the somatosensory cortex of Cox6a2-/- mice compared to wild-types (n=4 WT, 4 Cox6a2-/-; 2-month-old). C: two-tailed unpaired Student's t-test.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(D) In Cox6a2-/- mice, cortical PV+ interneurons showed a fewer number of synapses innervating principal neurons (n=3 WT, 3 Cox6a2-/-; 2-month-old). Two-tailed unpaired Student's t-test.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(E) To analyze changes in oxidative stress in PV+ interneurons, the somatosensory and motor cortices of WT and Cox6a2-/- mice were stained with an antibody against 8-OHdG, a marker of oxidative DNA damage. (F) 8-OHdG immunoreactivity was significantly higher in PV+ null in both cortices in Cox6a2-/- mice (n=4 WT, 4 Cox6a2-/-; 2-month-old). Two-tailed unpaired Mann-Whitney tests. ",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(G) The density of PNNs around PV+ interneurons residing in the somatosensory and motor cortices was analyzed by measuring the immunoreactivity of WFA that stains PNNs. (H) WFA immunoreactivity around PV+ cells was lower in both cortices in Cox6a2-/- mice (n=4 WT, 4 Cox6a2-/-; 2-month-old). Two-tailed unpaired Mann-Whitney tests. ",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(A) PV+ interneurons were sorted from cortices of PV-EGFP WT and Cox6a2-/- mice at P15 and processed for bulk RNA sequencing (n= 4 WT, 6 Cox6a2-/-; P15). Heatmap shows expression for top down- (red) and upregulated (blue) genes in Cox6a2-/- PV+ interneurons relative to their WT counterparts.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(B) Cox6a2 expression was effectively abolished in Cox6a2-/- PV+ interneurons. In addition, Cox6a2 knockout led to a decreased expression of Gad1 and Gad2 genes (n= 4 WT, 6 Cox6a2-/-). Two-tailed unpaired Mann-Whitney tests.",
    "ncbi_link": "Cox6a2: 12862
Gad1: 14415
Gad2: 14417"
  },
  {
    "caption": "(D) Representative images of PV+ interneurons from PV-CRE and PV-CRE;Cox6a2fl/fl mice showing PercevalHR fluorescence after excitation at 930 nm and 840 nm. White arrowheads indicate PercevalHR expressing cells. Scale bar: 20 μm.",
    "ncbi_link": "PercevalHR: 
Cox6a2: 12862
CRE: 2777477
PV: 19293"
  },
  {
    "caption": "(E) PV+ interneurons from PV-CRE;Cox6a2fl/fl mice exhibited significantly lower ATP-to-ADP ratios than PV+ interneurons from PV-CRE mice throughout the entire duration of the recordings (23 cells from 4 PV-CRE mice; 15 cells from 6 PV-CRE;Cox6a2-/- mice).",
    "ncbi_link": "Cox6a2: 12862
CRE: 2777477
PV: 19293"
  },
  {
    "caption": "(A,B) The resting membrane potential and amplitude of action potentials in WT and Cox6a2-/- PV+ interneurons, respectively. Two-tailed unpaired Student's t-tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(C,D) The threshold for action potentials increased over maturation in WT but not in Cox6a2-/- PV+ interneurons. As a result, the threshold for action potentials was significantly lower in P34-45 Cox6a2-/- PV+ interneurons when compared to their WT counterparts. D: two-tailed unpaired Student's t-tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(E,F) Trains of action potentials were evoked by 2 sec depolarizing current pulses. The amplitude difference (difference between the mean amplitude of 1st-10th action potentials and 190th-200th action potentials) was significantly higher in P34-45 Cox6a2-/- compared to WT PV+ interneurons. In addition, the amplitude difference decreased with maturation in WT but not in Cox6a2-/- PV+ interneurons. F: two-tailed unpaired Mann-Whitney tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(G) While in WT PV+ interneurons the maximal firing frequency increased during maturation, such increase was abolished by Cox6a2 knockout. Thus, maximal firing frequency reached during 2 sec depolarizing current pulses was lower in P34-45 Cox6a2-/- compared to WT PV+ interneurons. Two-tailed unpaired Student's t-tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(I,J) Cox6a2-/- PV+ interneurons showed a negative correlation between age and dendritic length and between age and full branch depth (maximal number of branches between the soma and a terminal dendritic point), which contrasted with the expected positive correlation between these parameters in WT PV+ interneurons. Linear regression of Pearson correlation.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(K,L) WT and Cox6a2-/- PV+ interneurons showed similar values for dendritic length and full branch depth at P22-P33. However, at P34-P45, Cox6a2-/- PV+ interneurons showed lower dendritic length and full branch depth than WT PV+ interneurons. Two-way ANOVA followed by Tukey's multiple comparisons tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(M,N) While younger WT and Cox6a2-/- PV+ interneurons have similar dendritic tree complexities (M), at the later stage of maturation Cox6a2-/- PV+ interneurons show a reduction in dendritic tree complexity in comparison to WT PV+ interneurons (N). Multiple t-tests, two-stage step-up method of Benjamini, Krieger and Yekutieli.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(B) In the OFT, Cox6a2-/- mice travelled a longer distance and moved faster than WT mice. Cox6a2-/- mice also moved more often from the outer zone to the inner zone of the arena. Two-tailed unpaired Student's t-tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(D) In the SIT, Cox6a2-/- mice also travelled a longer distance with higher mean velocity than WT mice. Additionally, both Cox6a2-/- and WT mice spent more time exploring the container with the stranger mouse than the empty container. Total distance moved, mean velocity, and f [number of crossings] outer to inner zone: two-tailed unpaired Student's t-test. Social interaction: two-way ANOVA followed by Tukey's multiple comparisons test.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(F) The startle responses were significantly lower in Cox6a2-/- mice when the loud stimulus (120 dB) was presented alone the first 5 times. Two-way ANOVA followed by Tukey's multiple comparisons tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "(G) The PPI of the acoustic startle response was similar at all pre-pulses for Cox6a2-/- and WT mice. Two-way ANOVA followed by Sidak's multiple comparisons tests.",
    "ncbi_link": "Cox6a2: 12862"
  },
  {
    "caption": "B. Relative miR-34c-5p and miR-155-5p expression levels (2deltaCt normalized to RNU48) in unstimulated and stimulated naive CD4 T cells of individual samples pooled to generate the sequencing libraries. mean ± SEM and p-value for differences in miR-155-5p expression (paired two tailed t-test) are shown. Comparison could not be performed for miR-34c-5p as it is undetermined in unstimulated samples.",
    "ncbi_link": "RNU48: 
miR-155-5p: 406947
miR-34c-5p: 407042"
  },
  {
    "caption": "C. Time course quantification of miR-34c-5p expression (top panel, 2deltaCt values) in three different donors.",
    "ncbi_link": "miR-34c-5p: 407042"
  },
  {
    "caption": "A, B. Comparison of the mean miR expression level by in TCR-stimulated naive CD4 T cell small RNA-seq libraries from uninfected and HIV-1NL4-3 (A) or HIV-2ROD (B) infected samples (24h). Only miRNAs with a minimum of 10 normalized read counts. Library normalization was performed using the mean normalization method available in Deseq package of Bioconductor (Anders & Huber, 2010). Lines indicate changes of +/- 1 log2 fold between samples (n=3, paired pools of three individual samples per library). miR-34c-5p is highlighted in black.",
    "ncbi_link": "miR-34c-5p: 407042"
  },
  {
    "caption": "C. Quantification of miR-34c-5p expression levels of the individual samples pooled to generate the sequencing libraries by qPCR (mean±SEM 2deltaCt values and p value from a paired two tailed t test; n=5).",
    "ncbi_link": "miR-34c-5p: 407042"
  },
  {
    "caption": "A. Cell-associated viral DNA levels (left), Tat mRNA levels (center), and RT activity levels (right) in cell culture supernatants in infected J34c cells vs. infected JØ cells at 24 and 48 hours post-infection. * p0.05 (paired two tailed t test).",
    "ncbi_link": "Tat: 155871"
  },
  {
    "caption": "C. Fold change levels for miR-34c-5p, cell-associated viral DNA level, Tat mRNA, and RT activity levels in J34c cells treated with miR-34c-5p antagomiR versus control antagomiR, 48 hours post-infection. Differences to control were found to be significant with a paired two tailed t test (p0.05).",
    "ncbi_link": "miR-34c-5p: 407042
Tat: 155871"
  },
  {
    "caption": "A. Hierarchical clustering of the 82 differentially expressed (DE) genes identified in Jurkat cell lines overexpressing miR-34c-5p (J34c-2 and J34c-5) vs control (JØ-1, 2 and 3 clones). Color scale represents mean centered log2 fold expression level across samples. Pie charts represent the relative proportion of predicted miR-34c-5p binding sites by the Miranda or PITA algorithms (or both) in down-regulated (top) and up-regulated (bottom) gene sets.",
    "ncbi_link": "miR-34c-5p: 407042"
  },
  {
    "caption": "B. qRT-PCR validation of selected genes. Plot represents the average percentage of target gene mRNA (normalized to GAPDH) in J34c vs JØ cells (all differences were found to be significant with a paired two tailed t test, P<0.05; n=5).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "B. Bottom: antagomiR to miR-34c-5p results in increased KAT2B mRNA levels compared to control-treated cells. Plot presents relative expression values for mRNA in 3 biological replicates; bars represent mean and SEM. Differences were found to be significant with p<0.05 (paired two tailed t test).",
    "ncbi_link": "KAT2B: 8850
miR-34c-5p: 407042"
  },
  {
    "caption": "C. Predicted target sites for miR-34c-5p in the PCAF/KAT2B mRNA(black bars) and miR-target hybridization for the two strongest sites (top); Luciferase assay with the pEZX renilla/firefly-PCAF/KAT2B 3'UTR reporter in HEK293 cells co-transfected with either the miR-34c-5p overexpression vector or pcDNA3 empty control (bottom). Differences were found to be significant with p<0.05 (paired two tailed t test, n=5).",
    "ncbi_link": "KAT2B: 8850
PCAF: 8850
miR-34c-5p: 407042"
  },
  {
    "caption": "a, Cells (wt, ∆atg18 or ∆atg18/∆atg21/∆hsv2 ()), with and without a plasmid expressing wt or a mutant form of Atg18) were grown in YPD, vacuoles were stained with FM4-64 and imaged by confocal microscopy. At least 10 confocal sections spaced at 300 nm were assembled into maximum projections. Images show cells before (0 min) and 15, 30 and 60 min after induction of vacuolar fragmentation by addition of 0.4 M NaCl. Red: FM4-64. Gray: DIC. Scale bar 5 µm.",
    "ncbi_link": "atg18: 850577
Atg18: 850577
atg21: 856004
hsv2: 853138"
  },
  {
    "caption": "atg18 cells expressing plasmids carrying Atg18-GFP or Atg18FGGG-GFP, a mutant in the lipid binding sites, were stained with FM4-64. a, Confocal z-stacks were taken before and 2, 6 and 10 min after addition of 0.4 M NaCl. Stacks were processed into maximum projections using ImageJ. Scale bar: 5 µm.",
    "ncbi_link": "atg18: 850577"
  },
  {
    "caption": "b, Same experiment as in a, but in a fab1 or vps34 background.",
    "ncbi_link": "fab1: 850574
vps34: 850941"
  },
  {
    "caption": "a. Autophagy measured with the pho8∆60 assay in atg18 cells complemented with wt, FGGG, SLoop or DLoop alleles of ATG18.",
    "ncbi_link": "atg18: 850577"
  },
  {
    "caption": "b. Same assay as in a, but in atg18 atg21 cells complemented with wt or SLoop versions of ATG18 and ATG21. Atg21SLoop contains K426F and F429K substitutions. Helical wheel projections for both Atg21 helices are given. The arrows indicate the magnitude of the hydrophobic moment.",
    "ncbi_link": "atg18: 850577
atg21: 856004"
  },
  {
    "caption": "c. Vacuole fragmentation in atg2 cells, assayed 15 min after a moderate hypertonic shock as in Fig. 1.",
    "ncbi_link": "atg2: 855479"
  },
  {
    "caption": "(a) Knockdown of RARα in NIH3T3 mouse fibroblasts was conducted using two different shRNAs, sh1 and sh2, compared to control (Ctr). Left, representative immunoblot. Actin is shown as loading control and full-length blots are shown in Supplementary Figure 21. Right, amounts of RARα in control and knockdown cells determined by densitometric quantification of immunoblots represented by the one shown on the left. Values are normalized for actin and expressed as multiples of control (None) values; n = 3.",
    "ncbi_link": "RARα: 19401"
  },
  {
    "caption": "(b) Rates of degradation of long-lived proteins in control and RARα(-) cells maintained in the presence or absence of serum for 12 h. Values are expressed as percentage of proteolysis; n = 3.",
    "ncbi_link": "RARα: 19401"
  },
  {
    "caption": "(a) Immunoblot for LC3-II in control mouse fibroblasts (Ctr) or those knocked down for RARα (RARα(−)) maintained in the presence or absence of serum for the indicated times. Where indicated, protease inhibitors (PI) against lysosomal proteolysis were added. Actin is shown as a loading control. 'I' and 'II' designate different forms of LC3, as described in the text. (b) Amounts of LC3-II determined by densitometric quantification of immunoblots. Values are expressed as fold change in value relative to serum-supplemented control cells; n = 4. (c) Ratio of the amounts of LC3-II in cells treated with protease inhibitors compared to untreated cells (None). Values are expressed as fold change in value relative to untreated cells; n = 4.",
    "ncbi_link": "RARα: 19401"
  },
  {
    "caption": "(f) Control and RARα(-) cells were transfected with the KFERQ-mCherry1 photoactivatable reporter, and after photoactivation they were maintained in medium with or without serum. Left, representative images. Graph shows quantification of the number of puncta per cell in >50 cells using the CMA reporter in at least four different fields. Nuclei are labeled with DAPI. Scale bars, 10 μm. In b, c, e and f, all values are mean ± s.e.m. Differences with control (marked with asterisk) or with serum-supplemented cells (marked with §) are significant for P 0.05. Full-field fluorescence images and full-length blots are shown in Supplementary Figures 2 and 21, respectively.",
    "ncbi_link": "RARα: 19401"
  },
  {
    "caption": "(c) Mouse fibroblasts were cotransfected with the human RARα (hRARα) receptor, a relevant reporter luciferase plasmid and the non-retinoid-regulated Renilla reporter to control for transfection. Values show relative luciferase units (RLU) detected in cells subjected to the indicated concentrations of ATRA or the three retinoid derivatives for 12h .",
    "ncbi_link": "luciferase: 
Renilla: 
RARα: 5914"
  },
  {
    "caption": "(d) Mouse fibroblasts were cotransfected with the human RARα (hRARα) receptor, a relevant reporter luciferase plasmid and the non-retinoid-regulated Renilla reporter to control for transfection.Cells transfected as in c were treated with 100 nM of ATRA alone or in the presence of the indicated concentrations of the three retinoid derivatives or the antagonist BMS614 for 12 h. Values are shown as RLU.",
    "ncbi_link": "luciferase: 
Renilla: 
RARα: 5914"
  },
  {
    "caption": "(e) Mouse fibroblasts were cotransfected with the human RXR receptor, a relevant reporter luciferase plasmid and the non-retinoid-regulated Renilla reporter to control for transfection. Values show relative luciferase units detected in cells subjected to the indicated concentrations of ATRA or the three retinoid derivatives for 12 h.",
    "ncbi_link": "luciferase: 
Renilla: "
  },
  {
    "caption": "(f) Mouse fibroblasts were cotransfected with the human RXR receptor, a relevant reporter luciferase plasmid and the non-retinoid-regulated Renilla reporter to control for transfection. Values show relative luciferase units detected in cells subjected to the indicated concentrations of ATRA or the three retinoid derivatives for 12 h. Cells transfected as in e were treated with 10 μM of ATRA alone or in the presence of the indicated concentrations of the three retinoid derivatives or the antagonist BMS614 for 12 h. Values are shown as RLU. Values in c-f are mean ± s.e.m.; n = 4-6.",
    "ncbi_link": "luciferase: 
Renilla: "
  },
  {
    "caption": "(a) Rates of degradation of long-lived proteins in control mouse fibroblasts or RARα(−) or LAMP-2A(−) (L-2A(−)) cells left untreated (None) or treated with 20 μM of the indicated compounds. Values are expressed as the fold change in proteolytic rate relative to the rate in untreated cells for each group; n = 3.",
    "ncbi_link": "LAMP-2A: 16784
RARα: 19401"
  },
  {
    "caption": "(b-d) Control mouse fibroblasts or RARα(−), LAMP-2A(−) or LAMP-2B(−) (L-2B(−)) cells were transfected with the KFERQ-mCherry1 photoactivatable reporter with or without the indicated compounds (20 μM). In b are shown the representative fields and high-magnification images (insets) for GR1. Nuclei are labeled with DAPI. Representative fields for GR2 and AR7 are shown in Supplementary Figure 13. Scale bars, 10 μm. (c,d) Average number of fluorescent puncta per cell quantified in >50 cells in at least four different fields in control cells and RAR(−) (c) or LAMP-2B(−) (d) cells. No puncta were detected in LAMP-2A(−) cells.",
    "ncbi_link": "LAMP-2A: 16784
LAMP-2B: 16784
RARα: 19401"
  },
  {
    "caption": "(b) mRNA levels of LAMP-2A in control mouse fibroblasts (left) or RARα(−) cells (right) treated with AR7 or paraquat (PQ) as in a; n = 4-5. Values are presented as fold change in mRNA relative to untreated cells.",
    "ncbi_link": "LAMP-2A: 16784
RARα: 19401"
  },
  {
    "caption": "(c) Cellular viability of control (left) or LAMP-2A(−) (right) fibroblasts exposed to 2 mM or 0.5 mM paraquat, respectively, and treated with the indicated compounds for 12 h before or after the paraquat treatment; n = 3.",
    "ncbi_link": "LAMP-2A: 16784"
  },
  {
    "caption": "(d) Viability of mouse fibroblasts transfected with the indicated concentrations of a plasmid encoding α-synuclein and left untreated (None) or treated with 1 mM paraquat alone or in the presence of 20 μM AR7; n = 3. In b-d, all values are mean ± s.e.m. Differences with cells that are untreated (marked with asterisk) or those treated only with paraquat (§) were significant for P 0.001. Full-length blots are shown in Supplementary Figure 21.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "(e) Immunoblot for α-synuclein (α-syn) in the same cells as in d. Top, higher-exposure blot to highlight oligomeric (oligo) species. Asterisk denotes nonspecific band. M, monomer; MW, molecular weight.",
    "ncbi_link": "α-synuclein: 20617"
  },
  {
    "caption": "H. Internalization (cytoplasm) and recycling (plasma membrane) of FGF10-stimulated HA-FGFR2b (green) transfected in BT549 stimulated for 0, 40 and 120 min.. Cells were depleted or not of TTP or RCP by a pool of siRNAs. TRITC-Tf is a marker of recycling (red). Nuclei are stained in blue. *, cells with receptor recycled to the plasma membrane. Scale bar, 5 μm.",
    "ncbi_link": "RCP: 80223
TTP: 23677"
  },
  {
    "caption": "(J) control or 40 min. FGF10- or TGFα-stimulated T47D left untreated or depleted of TTP, followed or not by transfection with siRNA resistant Flag-TTP (Flag-TTP*) or depleted of RCP followed or not by transfection with siRNA resistant RCP-GFP (RCP-GFP*) were immunoblotted with the indicated antibodies. **, non-specific band (J).",
    "ncbi_link": "Flag: 
GFP: 
RCP: 80223
TTP: 23677"
  },
  {
    "caption": "E. Co-localization of FGFR2 (red), EGFR (green), and the recycling marker Tf (blue) in T47D depleted of EGFR by siRNA followed by transfection with wt or T693A and stimulated or not with either FGF10 or TGFα for the indicated time periods. Scale bar, 5 μm.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "E, F Lysates from T47D (E) and BT20 (F) depleted of EGFR, transfected with wt or T693A, and stimulated or not with either FGF10 or TGFα for the indicated time intervals were immunoblotted with the indicated antibodies.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "A-D Percentage of EdU incorporation in T47D (A, C) or BT20 (B, D) depleted of EGFR or not, transfected with wt or T693A, and stimulated or not with FGF10 (A, B) or with TGFα (C, D) and pre-treated (C, D) or not (A, B) with FGF10 for 40 min. Values represent the median ± SD of N= 4. P value =<0.05 *, <0.01 **, <0.001*** (one-way ANOVA with Tukey test).",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(D) Immunofluorescence  of neurons  expressing BioID2-tau   or BioID2  (myc) or non-transduced control cells. Cells were incubated in biotin  medium (50 μM) or vehicle medium for 30 h prior to fixation and probed for biotin  (streptavidin, SA) and cell nuclei  (DAPI) (n = 3 biological replicates). BioID2-tau   and incorporated biotin co-localise in axons  and somata. Scale bar, 25 μm.",
    "ncbi_link": "myc: 
tau: 4137"
  },
  {
    "caption": "(B) Immunoblot  of combined brain  lysates from mice  (P35) expressing BioID2-tau   or BioID2  control (n = 4 biological replicates) probed for myc-tagged BioID2  and BioID2-tau. Controls: lysates from (1) BioID2- or (2) BioID2-tau-expressing and (3) non-transduced mouse brain. Loading, glyceraldehyde-3-phosphate dehydrogenase (Gapdh). *, unspecific band. Relative quantification confirmed similar expression levels of BioID2  and BioID2-tau. Means ± S.E.M. ns, not significant (Student's t-test)",
    "ncbi_link": "tau: 4137"
  },
  {
    "caption": "(B-C)  Co-immunoprecipitation (Co-IP) of tau  and NSF   from mouse brain. (B) Endogenous and transgenic tau  were immunoprecipitated  from mouse brain  lysates of tau-/-, ALZ17tg or ALZ17non-tg mice  using anti-tau  antibody followed by immunoblot  probed for NSF, tau  and α-actin. Endogenous NSF  was co-immunoprecipitated  with transgenic and endogenous tau  from ALZ17tg or ALZ17non-tg but not from tau-/- with. GAPDH, input loading control (n = 3 biological replicates). Recombinant tau  and NSF  served as controls. (C) Densitometric  quantification of co-IP results in (B). Data information: Values are means ± S.E.M (normalized to control). Adjusted p-values: ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test.",
    "ncbi_link": "tau: 17762
tau: 4137"
  },
  {
    "caption": "Co-IP  of HA-tagged tau  with NSF  from 293T  cells. (E) Co-IP of NSF  with haemagglutinin  (HA)-tagged tau  variants from cultured cells. HA-tagged tau  variants and NSF  were expressed in 293T  cells followed by immunoprecipitation  using HA  antibody and immunoblot  probed for NSf, tau  and GAPDH. (n = 3 biological replicates).",
    "ncbi_link": "HA: 
tau: 4137
NSF: 4905"
  },
  {
    "caption": "(A) Impaired AMPA-type glutamate receptor  surface expression  in cultured tau-/- neurons. Cortical tau+/+ or tau-/- neurons  were surface biotinylated after incubation with non-competitive NMDAR  antagonist MK-801  (50 μM, 3 min) and/or GABAAR antagonist bicuculline (30 μM, 10 min) at 37°C. Surface GluA1  levels were detected by immunoblot  after with streptavidin  (SA) enrichment. Input was probed for total cellular GluA1, NSF, tau   and  βIII-tubulin. (n = 3 biological replicates) Input and SA-enrichment from non-surface biotinylated neurons  served as negative controls. (B) Reduced neuronal  surface GluA1  in tau-/- neurons. Quantification of tau+/+ and tau-/- surface GluA1  upon treatment and SA-enrichment shown in (A). Data information: Values are means ± S.E.M (normalized to control). Adjusted p-values: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test. ",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "(C) Cell surface GluA1  and total NSF immunostaining  in primary mouse hippocampal neurons (DIV15). Tau+/+, tau-/- neurons  and tau-/- expressing human tau  (tau-/-.AAVtau) were treated with either vehicle (Veh; DMSO) or MK-801 (50 μM) for 3 min. Representative confocal  images of whole cell (left) and neurites  (right) are shown (n = 3 biological replicates). NSF, surface GluA1  and cell nuclei  (DAPI) were visualized. Scale bar, 25 μm. (D-E) Quantification of neurite  surface GluA1  and neurite NSF  relative to tau+/+ Veh control. Reduced surface GluA1  (D) and total NSF  (n = 10-12 neurites  from 3 biological replicates) (E) localized  to neurites  in tau-/- neurons  treated with MK801  (n = 21-23 neurites  from 3 biological replicates). Data information: Values are means ± S.E.M (normalized to control). Adjusted p-values: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test. ",
    "ncbi_link": "Tau: 17762
tau: 17762
tau: 4137"
  },
  {
    "caption": "(F) Changes in secondary dendrite GluA2 expression  in neurons  (DIV18) upon cLTP/cLTD  induction. Tau-/- neurons  were transfected with tau  at DIV12 (= tau-/-.tau) or mock transfected (tau-/-). Cells were stained  for GluA2, dendritic  marker Map2, and NSF  at 2 h post-cLTP/cLTD  induction or treatment with control artificial cerebrospinal fluid  (aCSF). Dendritic GluA2  cluster analysis was based on GluA2-Map2  binary intensity map. Representative insets from n = 10-20 dendrites  per condition from 2 mice  per genotype. Scale bar, 3 μm. (G) Quantification of GluA2  mean intensity relative to Map2  area and normalised to aCSF controls. Secondary dendrite GluA2  increased in tau-expressing (tau+/+ and tau-/-.tau) neurons  upon cLTP  induction. (n = 10-19 dendrites  from 3 biological replicates). Data information: Values are means ± S.E.M (normalized to control). Adjusted p-values: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test. ",
    "ncbi_link": "Tau: 17762
tau: 4137
tau: 17762"
  },
  {
    "caption": "(H) Representative immunostaining for whole-cell NSF  and GluA2  in tau+/+, tau-/- and tau-transfected tau-/- (tau-/-.tau) neurons  at 2 h post-cLTP/cLTD  induction or treatment with control artificial cerebrospinal fluid  (aCSF). (n = 3-6 biological replicates per condition with 10-20 cells each). Scale bar, 10 μm. Arrows indicate areas of marked co-distribution. (I) Co-localisation analysis of NSF  and GluA2  upon chemical LTP/LTD  induction. Note significantly higher proportional co-distribution of NSF  and GluA2  in tau-expressing (tau+/+ and tau-/-.tau) cells upon cLTP  induction. (n = 3-6 cells from 3 biological replicates). Data information: Values are means ± S.E.M (normalized to control). Adjusted p-values: ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test. ",
    "ncbi_link": "tau: 17762
tau: 4137"
  },
  {
    "caption": "(B) Examples of sagittal sections of tau-/- and AAV.syn-hTau-injected tau-/- (tau-/-.AAVtau) mice  showing localized AAV-mediated expression of eGFP  or tau  and position of infusion cannulas  ending in the hippocampus  (dashed line). GluA1, immunolabelling  for GluA1 AMPA receptor subunit. Scale bar, 50 μm.",
    "ncbi_link": "tau: 17762
Tau: 4137
tau: 4137"
  },
  {
    "caption": "(C) Cued fear conditioning memory in tau+/+, tau-/- and tau-/-.AAVtau mice  upon bilateral infusion of TAT-NSF   or TAT-Scr. Due to infusion of Tat-fusion peptides occurring under brief isoflurane anaesthesia, a general anaesthesia (GA) control is included. Note that infusion of  TAT-NSF lowers memory performance to comparable levels in tau+/+, tau-/- and tau-/-.AAVtau mice. (n = 2-5 biological replicates) Data information: Values are mean ± 95% confidence intervals. Adjusted p-values: ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test.",
    "ncbi_link": "tau: 17762
tau: 4137"
  },
  {
    "caption": "(D) Novel object preference  (fold preference over familiar object) in tau+/+, tau-/- and tau-/-.AAVtau mice  upon bilateral infusion of TAT-NSF  or TAT-Scr (n = 2-5 biological replicates). Due to infusion of Tat-fusion peptides occurring under brief isoflurane  anaesthesia, a general anaesthesia (GA) control is included (n = 2 for GA). Note that infusion of TAT-NSF  lowers object discrimination to comparable levels in tau+/+, tau-/- and tau-/-.AAVtau mice. Data information: Values are mean ± 95% confidence intervals. Adjusted p-values: ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test.",
    "ncbi_link": "tau: 17762
tau: 4137"
  },
  {
    "caption": "(E) ATPase assay of recombinant NSF  upon incubation with tau coimmunoprecipitates  (tau5) from cortical   lysates of indicated genotypes, including from tau-transgenic mice  (ALZ17, Tau58/2) (n = 5-8 biological replicates). IgG, control immunoprecipitate  with non-specific IgG from tau+/+ lysate. Data information: Values are mean ± 95% confidence intervals. Adjusted p-values: ***p < 0.001, **p < 0.01, *p < 0.05, ns, not significant, ANOVA with Sidak's test.",
    "ncbi_link": "tau: 4137
tau: 17762"
  },
  {
    "caption": "C-E. Luciferase reporter assay in HeLa  cells using the synthetic miR-Control or miR-182-3p in combination with the wild type (C) or the mutant 3'UTR of TRF2  construct (D) or the wild type 3'UTR of TRF1  (E). Data information: data are shown as mean ± SD. Three independent experiments were performed (n=3). P values are determined by Mann-Whitney test.",
    "ncbi_link": "miR-182-3p: 406958
TRF1: 7013
TRF2: 54386"
  },
  {
    "caption": "F,G. Western blotting for TRF2  expression in Telomerase   Positive (HeLa, HCT116, MDA-MB-231, MDA-MB-436) and ALT  positive (U2-OS, Saos-2) cells transiently transfected with miR-Control or miR-182-3p. Upper panel shows the quantification of TRF2  expression. Bottom panel, representative images are shown, actin  was used as loading control. Data information: data are shown as mean ± SD. Three independent experiments were performed (n=3). P values are determined by Mann-Whitney test.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "H. U2-OS cells transiently transfected with the miR-Control, miR-182-3p or miR-182-3p inhibitor were assayed by quantitative immunofluorescence  for TRF2  three days post-transfection. Left panel, representative images. Scale bar: 10µm. Right panel, quantification of TRF2  fluorescence intensity. a.f.u. arbitrary fluorescence units. N=number of analysed nuclei. Red bar indicates mean value. Data information: Three independent experiments were performed (n=3). P values are determined by Student's t-test; for (H)",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "E. Quantification of TIFs in MDA-MB-231 cells over-expressing TRF2  or an empty vector (pBabe), transfected with indicated miRNAs. The mean number of TIFs per nucleus  was quantified. F. Representative images and enlargements relative to the experiment described in E. White arrowheads indicate  co-localizations events. Scale bar: 10µm. Data information: data are shown as mean ± SD. Three independent experiments were performed (n=3). P values are determined by unpaired two-tailed t test. At least 60 nuclei  were analysed for each experimental condition. All the experiments were performed three days post-transfection with the indicated miRNAs",
    "ncbi_link": "TRF2: 54386"
  },
  {
    "caption": "G. Quantification of PIFs in  MDA-MB-231  cells over-expressing TRF2  or an empty vector (pBabe), transfected with indicated miRNAs. The γH2AX  positive cells with ≥1 PIFs per nucleus  were analysed. H. Representative images relative to the experiment described in G. White arrowheads indicate  co-localizations  events. Scale bar: 10µm. Data information: For G data are shown as mean ± SD. Three independent experiments were performed (n=3). P values are determined by unpaired two-tailed t test. At least 60 nuclei  were analysed for each experimental condition. All the experiments were performed three days post-transfection with the indicated miRNAs",
    "ncbi_link": "TRF2: 54386"
  },
  {
    "caption": "A,B. MDA-MB-436  and  MDA-MB-231  cells underwent two rounds of transfection with miR-Control, miR-182-3p or miR-182-3p inhibitor. Starting from the day of the second transfection, cell confluence was monitored by Incucyte every 24h up to a maximum of 3 days. The percentage of  cell confluence  was analysed. Data information: For A,B data are shown as mean ± SEM. three independent experiments were performed (n=3). P values are determined by unpaired two-tailed t test.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "E. Two-dimensional scatter plots of Annexin V  analysis performed in MDA-MB-436  at the end of the second cycle of transfection with miR-Control, miR-182-3p or miR-182-3p inhibitor. Red boxes indicate early and late apoptotic cells. F. Quantification of Annexin V positive cells (%) of experiment described in E. G. Two-dimensional scatter plots of  Annexin V analysis performed in MDA-MB-231 as described in E. H. Quantification of  Annexin V  positive cells (%) of experiment described in G. Data information: For F,H data are shown as mean ± SD. P values are determined by unpaired two-tailed t test. For F, H two different biological replicates were performed.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "I,J. MDA-MB-436 cells over-expressing TRF2  or an empty vector (pBabe) were transiently transfected with indicated miRNAs and  cell count (I) or apoptosis  (J) analysis was performed 72h post-transfection. Data information: For ,I,J, data are shown as mean ± SD. For I, three independent experiments were performed (n=3). P values are determined by unpaired two-tailed t test. For J, two different biological replicates were performed.",
    "ncbi_link": "TRF2: 54386"
  },
  {
    "caption": "A. Western blotting  for TRF2  expression in BJ  cells transiently transfected with miR-Control or miR-182-3p. The graph represents the quantification of three independent experiments. Representative images are shown, actin  was used as loading control. Unspecific bands are indicated with (*).",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "E.  Cells number  of BJ  cells was analysed by automatic cell count at the end of the second round of transfection with miR-Control or miR-182-3p. Data information: a student t test was used to calculate statistical significance. P values are indicated.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "G. β-Galactosidase assay  in BJ  cells after two rounds of transfection with mimic miR-Control or miR-182-3p. Left panel: analysis of β-Galactosidase positive cells. Right panel: representative images. Data information: a student t test was used to calculate statistical significance. P values are indicated.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "A,B. MDA-MB-231 (A) and MDA-MB-436  (B) tumor xenografts  were treated with LNPs-empty, LNPs-miR-Control or by LNPs-miR-182-3p when the tumors became palpable. Mice  were treated 6 times  by intravenous  tail vein injections with 20µg of LNPs-miR-Control, LNPs-miR-182-3p or equivalent volume of LNPs-empty as indicated in the scheduling. The mean of tumor volumes  (n=5 per group) is shown. Data information: For A, B data are shown as mean ± SD. P values are determined by unpaired two-tailed t test",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "C,D. Tumors from mice  treated in A and B were processed to measure miR-182-3p expression by  TaqMan qPCR. Data information: For C, D the line in the middle of the box plot denote a median value, the limits of box represent the interquartile range (25th to 75th percentiles), while, the whiskers denote the minimum to maximum values. , P values are determined by unpaired two-tailed t test;",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "G, H. Luminescent MDA-MB-436 cells were injected into the brain  and monitored by IVIS imaging system. After one week from implant, treatment with LNPs-miR-Control and LNPs-miR-182-3p was performed as indicated in A and B. Representative images from in vivo (upper panel) or ex-vivo (bottom panel) brain tumors are shown in G. Boxplots (H) show the measurement of photons for each  brain tumor (n=5 per group) acquired at the indicated times. Data information: For H, the line in the middle of the box plot denote a median value, the limits of box represent the interquartile range (25th to 75th percentiles), while, the whiskers denote the minimum to maximum values. For H, P values are determined by unpaired two-tailed t test;",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "A,B. PDTCs  #1 and #2 underwent two rounds of transfection with miR-Control or miR-182-3p. Three days after the second transfection, miR-182-3p  and TRF2  expression were analysed by TaqMan qPCR   and western blotting, respectively. Actin  was used as loading control. Data information: data are shown as mean ± SD. P values are determined by unpaired two-tailed t test For the experiments showed in A, B two or three biological replicates were performed, respectively.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "E. NSG mice  implanted  with breast  PDTX (#2) were treated with LNPs-empty, LNPs-miR-Control or LNPs-miR-182-3p  as indicated in the scheduling. Caliper measurement of tumors were taken at the indicated days. The mean of  tumor volumes (n=5 per group) is shown. Data information: data are shown as mean ± SD. P values are determined by unpaired two-tailed t test;",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "F.  miR-182-3p expression  of tumors from mice  treated in (E) was assayed by TaqMan qPCR. Data information: data are shown as mean ± SD. P values are determined by unpaired two-tailed t test",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "A. Representative images of intestine  sections from mice  previously treated with LNPs-Empty or LNPs-miR-182-3p. H&E staining  (scale bar: 200μm) and IHC  analysis with TRF2  or γH2AX  antibodies are shown (scale bar: 50μm). B,C. Quantification of TRF2 expression  as immunoreactivity score (IRS) (B) and of γH2AX  positive cells (%) (C) on intestine  samples. D. Representative H&E (scale bar: 200μm), TRF2  and γH2AX  images of skin  samples corresponding to LNPs-Empty or LNPs-miR-182-3p treated animals (scale bar: 50μm). E,F. Quantification of TRF2 expression as immunoreactivity score (IRS) (E) and of γH2AX  positive cells (%) (F) on skin  samples. G. Representative H&E (scale bar: 200μm), TRF2  and γH2AX  images of  bone marrow samples corresponding to LNPs-Empty or LNPs-miR-182-3p treated animals (scale bar: 50μm). H,I. Quantification of TRF2 expression  as immunoreactivity score (IRS) (H) and of γH2AX  positive cells (%) (I) on  bone marrow samples. Data information: For B,C,E,F,H,I, data are shown as mean ± SD. A Mann-Whitney test t test was used to calculate statistical significance. Four mice  per group were analysed the points represent the number of field analysed for each condition.",
    "ncbi_link": "miR-182-3p: 406958"
  },
  {
    "caption": "Representative Ca2+ signals in sperm from a patient with deafness-infertility syndrome lacking functional CatSper channels (CATSPER2-/-) (red) and a healthy donor (black), evoked by progesterone, PGE1, NH4Cl, or ionomycin. NH4Cl increases the intracellular pH. Bar graph: Amplitudes (n = 4; mean ± SD) of Ca2+ signals in CATSPER2-/- sperm",
    "ncbi_link": "CatSper: 117155
CATSPER2: 117155"
  },
  {
    "caption": "Representative monovalent CatSper currents in CATSPER2-/- sperm (blue, green, orange, purple, brown) and in sperm from a healthy donor (black) and corresponding current-voltage relationship (right). The membrane voltage was stepped from -100 mV to +100 mV in increments of 10 mV from a holding potential of -80 mV. Outward and inward current amplitudes (mean ± SD) at +100 mV and -100 mV, respectively, in CATSPER2-/- sperm (color code: panel B) and sperm from healthy donors (black).",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "Representative immunocytochemical staining of control sperm from healthy donors and CATSPER2-/- sperm form DIS patients using antibodies directed against CatSper 3 (D) or CatSper 4 (E); DNA was labelled with DAPI (blue). Scale bars represent 10 µm.",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "3D-STORM images in xy-projection of CATSPER2-/- sperm (left) labelled with the anti-CatSper 3 (upper panel) and anti-CatSper 4 (lower panel) antibody. Axial projection of the boxed regions (right). Scale bars represent 5 µm in xy-projections and 200 nm in axial projections.",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "Representative distribution of rotation frequencies of freely swimming CatSper-deficient sperm incubated under non-capacitating (0 mM bicarbonate; black; n = 73) and capacitating conditions (25 mM bicarbonate; red; n = 272).",
    "ncbi_link": "CatSper: 117155"
  },
  {
    "caption": "Rolling frequency (mean ± SD) of freely swimming CATSPER2-/- sperm incubated under non-capacitating (0 mM bicarbonate, n = 1009) and capacitating (25 mM bicarbonate, n = 946) conditions.",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "Rolling frequency (mean ± SD) of freely swimming CATSPER2-/- sperm in 0 (n = 457), 0.2 (n = 389), and 1 % (w/v) (n = 187) methyl cellulose.",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "Image series of a CATSPER2-/- sperm cell optically trapped perpendicular to the optical axis; images were obtained at t = 0, 75, 150, and 225 ms. Scale bar represents 10 µm. Image series of a CATSPER2-/- sperm cell optically trapped parallel to the optical axis; images were obtained at t = 0, 60, 195, and 320 ms. The red bar indicates the 360° rotation of the tip of the head. Scale bar represents 10 µm. Representative time courses of the rotation frequencies of optically trapped CATSPER2-/- sperm (each sperm is represented in a different color). Error bars indicate the full width at half prominence of the frequency peaks determined by the fast Fourier analysis.",
    "ncbi_link": "CATSPER2: 117155"
  },
  {
    "caption": "Left: Bright-field image series of a freely swimming wild-type sperm cell at t = 0, 151, and 303 ms. Scale bar represents 10 µm. Right: Rotation frequency (mean ± SD) of 24 freely swimming wild-type sperm. Left: Bright-field image series of a freely swimming Catsper1-/- sperm cell at t = 0, 151, and 294 ms. Scale bar represents 10 µm. Right: Rotation frequency (mean ± SD) of 24 freely swimming Catsper1-/- sperm.",
    "ncbi_link": "Catsper1: 117144"
  },
  {
    "caption": "A, B Bottom panels: gene annotation track (mm10); the activated gene is marked in green and the location of the TALE-VP64 target sequence is shown by the vertical dashed green line. Middle panels: DamID tracks of NL interactions in control cells ("control", blue line) and cells expressing TALE-VP64 ("experimental", red line). n indicates the number of independent biological replicates that were combined. Noise was suppressed by a running mean filter of indicated window size. Shading between the lines corresponds to the color of the sample with the highest value. Arrowheads on the right-hand side mark the 5th and 95th percentiles of genome-wide DamID values. Top panels: domainograms; for every window of indicated size (vertical axis) and centered on a genomic position (horizontal axis) the pixel shade indicates the ranking of the change in DamID score (experimental minus control) in this window compared to the genome-wide changes in DamID scores across all possible windows of the same size. Blue: DamID score is highest in control samples; red: DamID score is highest in experimental samples (color key on the right of panel (a)). In (a) activation of Sox6 was the experimental perturbation, activation of Nrp1 (which is located on a different chromosome) served as control; in (b) activation of Nrp1 was the experimental condition and activation of Sox6 served as control.",
    "ncbi_link": "Nrp1: 18186
Sox6: 20679"
  },
  {
    "caption": "(a-b) Plots as in Figure 1, showing changes in Lamin B1 DamID signals upon CRISPRa activation of NLGN1 (a) and SOX6 (b). Control cells were treated either without sgRNA or with one of various sgRNAs targeting promoters on different chromosomes. Vertical green dotted lines mark the position of the sgRNA target sequence.",
    "ncbi_link": "NLGN1: 22871
SOX6: 55553"
  },
  {
    "caption": "A-C CRISPRa activation of ADAM22 (a), ABCB1 (b) and PTN (c) in human RPE-1 cells. Top panels visualize DamID data similar to Figure 2a-b. Middle panels show maps of replication timing at the same resolution and in the same plotting style as panels, except that different colors are used as indicated. Bottom panels show gene track, with activated gene highlighted in green.",
    "ncbi_link": "ABCB1: 5243
ADAM22: 53616
PTN: 5764"
  },
  {
    "caption": "Changes in NL interactions after CRISPRa activation of MLK4 in human RPE-1 cells. Visualization of DamID data as in Figure 2a-b.",
    "ncbi_link": "MLK4: 84451"
  },
  {
    "caption": "(a) DamID domainograms of NL interactions after activation of CCSER1, GRID2, or both. All data are from human RPE-1 cells.",
    "ncbi_link": "CCSER1: 401145
GRID2: 2895"
  },
  {
    "caption": "(b) DamID domainograms after activation of ADAM22, ABCB1, or the genes ABCB4, ABCB1, ADAM22 and RUNC3B simultaneously. All data are from human RPE-1 cells. DamID data of activation of ADAM22 and ABCB1 alone are same as in Figure 4a, b.",
    "ncbi_link": "ABCB1: 5243
ABCB4: 5244
ADAM22: 53616
RUNC3B: 154661"
  },
  {
    "caption": "(a) DamID profiles of the 129Sv allele of the Morc1 locus with deletions of the promoters of Morc, Morc1 and DppA2 (deletions marked by yellow vertical boxes), and in control cells. (b) Same as (a), but for the non-mutated Cast alleles. ",
    "ncbi_link": "DppA2: 73703
Morc1: 17450
Morc: 17450"
  },
  {
    "caption": "(c-d) Same design as (a-b), but with only a single mono-allelic deletion of the Morc promoter (vertical yellow box).",
    "ncbi_link": "Morc: 17450"
  },
  {
    "caption": "(e-f) Effect of PAS insertion on NL interactions of Cobl gene locus. Same design as (a-b) but with insertion of a PAS (located at red triangle and vertical dotted line) that truncates the 129Sv allele of the Cobl transcription unit. 129Sv allele is shown in (e), non-mutated Cast allele in (f). Clones with Morc1 locus mutations (each assayed in four independent biological replicates) served collectively as control in (e-f)",
    "ncbi_link": "Cobl: 12808
Morc1: 17450"
  },
  {
    "caption": "Relative 2-hydroxyglutarate (2-HG) production level based on targeted CE-MS metabolomics comparing among WT and GR cells (left panel: T24, right panel: UMUC3). The data are shown as the means ± SDs (n=3, biological replicates) and were analyzed by Student's t test. *p<0.05, **p<0.01. Relative mRNA expression levels of IDH2 and EGLN1 genes compared between WT and GR cells (left panel: T24, right panel: UMUC3). The expression levels were analyzed by Student's t test and plotted relative to expression levels in WT cells. The data are shown as the means ± SEs (n=3, biological replicates. *p<0.05, ***p<0.001.",
    "ncbi_link": "EGLN1: 54583
IDH2: 3418"
  },
  {
    "caption": "Western blot analysis of Hif-1α, GLUT1, G6PD, TIGAR, TKT, CTPS1, PKM2, LDHA, and β-actin after transfection with NTC and IDH2-targeting (siHIF1A#1 and #2) siRNAs (left: T24GR, right: UMUC3GR).",
    "ncbi_link": "HIF1A: 3091
IDH2: 3418"
  },
  {
    "caption": "Relative mRNA expression levels of IDH2, GLUT1, G6PD, TIGAR, TKT, CTPS1, PKM2, and LDHA in cells transfected with siIDH2#1 and #2 compared with cells transfected with siNTC (upper: T24GR, lower: UMUC3GR). The data are shown as the means ± SEs (n=3, biological replicates) and were analyzed by Student's t test, and plotted relative to expression levels in GR cells transfected with siNTC. *p<0.05, **p<0.01, ***p<0.001.   Western blot analysis of IDH2, PHD2, HIF-1α, G6PD, GLUT1, TIGAR, TKT, CTPS1, PKM2, LDHA, and β-actin after transfection with NTC and IDH2-targeting (siIDH2#1 and #2) siRNA (left: T24GR, right: UMUC3GR).  ",
    "ncbi_link": "CTPS1: 1503
G6PD: 2539
GLUT1: 10755
IDH2: 3418
LDHA: 3939
PKM2: 5315
TIGAR: 57103
TKT: 7086"
  },
  {
    "caption": "Graph showing the viability of GR cells exposed to various concentrations of GEM for 48 hr after transfection with NTC and IDH2-targeting (siIDH2#1 and #2) siRNA (left: T24GR, right: UMUC3GR) The data are shown as the means ± SDs (n=3, biological replicates).",
    "ncbi_link": "IDH2: 3418"
  },
  {
    "caption": "Relative mRNA expression levels of IDH2, EGLN1, Hif-1α, G6PD, TIGAR, TKT, and CTPS1 between J82 wild-type cells (J82WT) and J82 cells with IDH2 overexpression (J82-IDH2ox cells). The data are shown as the means ± SEs (n=3, biological replicates). The expression levels were analyzed by Student's t test and are plotted relative to the expression levels in WT cells. *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "CTPS1: 1503
EGLN1: 54583
G6PD: 2539
Hif-1α: 3091
IDH2: 3418
TIGAR: 57103
TKT: 7086"
  },
  {
    "caption": "Western blot analysis of IDH2, PHD2, Hif-1α, G6PD, TIGAR, TKT, CTPS1, and β-actin in J82WT and J82-IDH2ox cells.",
    "ncbi_link": "IDH2: 3418"
  },
  {
    "caption": "Graph showing the viability of J82WT and J82-IDH2ox cells exposed to various concentrations of GEM for 48 hr. The data are shown as the means ± SDs (n=3, biological replicates) and were analyzed by Student's t test. ***p<0.001.",
    "ncbi_link": "IDH2: 3418"
  },
  {
    "caption": "NADPH/NADP ratios of GR cells transfected with NTC, IDH2 siRNA#1, and siRNA#2 (left: T24GR, right: UMUC3GR). The data are shown as the means ± SDs (n=3, biological replicates) and were analyzed by Student's t test. ** p<0.01.",
    "ncbi_link": "IDH2: 3418"
  },
  {
    "caption": "E: Western blot analysis of PITRM1 in primary fibroblasts (left) and skeletal muscle (right) of controls (CTR) and subject II-2. Densitometric quantification using the Genetools software is shown below the blots. In blue is PITRM1WT and in red PITRM1R183Q.",
    "ncbi_link": "PITRM1: 10531"
  },
  {
    "caption": "F: proteolytic activity on two fluorescent oligopeptides (AnaSpec), reported at the bottom of each histogram, by 6-His tagged PITRM1WT and PITRM1R183Q proteins expressed in E. coli and affinity-purified by Ni-agarose chromatography. Values are expressed as arbitrary units per sec per µg of protein (a.u. s-1µg-1). Experiments were performed in duplicate.",
    "ncbi_link": "PITRM1: 10531"
  },
  {
    "caption": "G: degradation rate of Aβ1-42 by purified 6-His tagged PITRM1WT and PITRM1R183Q proteins. Quantification of these experiments is displayed below the blots. Experiments were performed in duplicate.",
    "ncbi_link": "PITRM1: 10531"
  },
  {
    "caption": "A: cell growth in glucose (GLU) and galactose (GAL). C29V, C47V, TpLV: immortalized fibroblast cell lines from control individuals; PITRM1V: immortalized fibroblasts from subject II-2, carrying the PITRM1R183Q mutation. pLKO.1: empty vector; sh38: shRNA38; sh41: shRNA41. Each cell line was measured six times. Error bars indicate ±SD. Statistic analysis was by two-way ANOVA post-hoc Bonferroni test ***p<0.001.",
    "ncbi_link": "PITRM1: 10531"
  },
  {
    "caption": "C: co-localization of PITRM1 (red) with TOM20 (T20, green) in human fibroblast cells from a control (CTR) and subject II-2. Note that the intensity of PITRM1 immunofluorescence is much lower in II-2 cells than in CTR cells (see main text for further details). Nuclei are stained in blue by DAPI. A white bar corresponds to 10 µM.",
    "ncbi_link": "PITRM1: 10531"
  },
  {
    "caption": "A: oxidative growth. W303-1Bcym1Δ strains harbouring the wild-type CYM1 allele (CYM1wt), the cym1R163Q mutant allele or the empty vector were serially diluted from 107 to 104 cells/ml. Five microliters of each dilution were spotted on SC agar plates without uracil, supplemented with 2% glucose, 2% glycerol or 2% ethanol. Plates were incubated at 37°C for 3-7 days.",
    "ncbi_link": "CYM1: 852041"
  },
  {
    "caption": "B: oxygen consumption rate (OCR). Cells grown at 37°C SC medium without uracil were supplemented with 0.5% glucose. Values were normalized to the OCR of the CYM1wt strain (49 nmol O2 min−1 mg−1) and represented as the mean of at least three values ± SD. Statistical analysis was by unpaired, two-tail Student's t test: ***p<0.001.",
    "ncbi_link": "CYM1: 852041"
  },
  {
    "caption": "D: respiratory chain complex activities. Biochemical activities of Succinate Quinone DCPIP Reductase, SQDR (CII), NADH-cytochrome c oxidoreductase activity NCCR (CIII), and cytochrome c oxidase (CIV) were measured on a mitochondrial-enriched fraction from cells grown at 37°C as in panel B. Values were normalized to that of CYM1wt strain and represented as the mean of three independent experiments ± SD. Statistical analysis was by unpaired, two-tail Student's t test: **p<0.01; ***p<0.001.",
    "ncbi_link": "CYM1: 852041"
  },
  {
    "caption": "E: Western-blot using an anti-HA monoclonal antibody visualizing the CYM1wt and cym1R163Q recombinant proteins both fused in frame with the HA epitope on the C-terminus. Western-blot analysis on total protein extract. Total protein extracts were obtained by strains expressing HA-tagged CYM1wt and cym1R163Q. PGK was used as a loading control and signals were normalized to the wt. The quantification was performed on 5 independent blots.F: prolonged exposure of a Western-blot containing the CYM1wt and cym1R163Q recombinant proteins reveals the presence of a band corresponding to a degradation product in the cym1R163Q lanes (arrow).",
    "ncbi_link": "CYM1: 852041"
  },
  {
    "caption": "A: Western-blot analysis of Pitrm1 protein in brain, muscle and liver of two 4-mo male Pitrm1+/- mice and two Pitrm1+/+ littermates. Densitometric analysis is reported in the histograms below the blots. Pitrm1+/+ is in blue, Pitrm1+/- in red. Error bars indicate ±SD",
    "ncbi_link": "Pitrm1: 69617"
  },
  {
    "caption": "B: representative hindlimb-clasping phenomenon is shown in a 4 mo Pitrm1+/- male mouse, consisting in strong adduction of the hindlimbs when the animal is suspended by the tail; a littermate Pitrm1+/+ control displays the normal reflex, consisting in wide abduction of the limbs. All examined Pitrm1+/- animals displayed this abnormal reflex from 2 months of age.",
    "ncbi_link": "Pitrm1: 69617"
  },
  {
    "caption": "C: rotarod test. Blue and red lines refer to Pitrm1+/+ (n=9) and Pitrm1+/- (n=7) 4 mo animals, respectively. Error bars indicate ±SD. Statistical analysis was by unpaired, two-tail Student's t test. *p<0.05; ** p<0.01.",
    "ncbi_link": "Pitrm1: 69617"
  },
  {
    "caption": "B: morphological analysis of an AD subject and of Pitrm1+/- and Pitrm1+/+ mouse brains. TF: Thioflavin T (thalamus); CR: Congo-red (brain cortex); PL: polarised light (same sections as those stained with CR); Aβ1-42 immunostaining (pons); Ub: ubiquitin immunohistochemistry shown as brownish staining (brain cortex). The white bar indicates 20 µm.",
    "ncbi_link": "Pitrm1: 69617"
  },
  {
    "caption": "A: upper panel: import of Aβ1-42 into mitochondria; lower panel: relative quantification from two independent experiments. Values of Aβ1-42 signal were normalized to HSP60 signal and the resulting value at 5 min without trypsin was arbitrarily chosen as 1. Error bars indicate ±SD. Statistical analysis was by unpaired, two-tail Student's t test. *p<0.05.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "B: upper panel: pulse and chase experiment to assess clearance of Aβ1-42; lower panel: quantification from three independent experiments. Values of Aβ1-42 signal were normalized to HSP60 signal and the pulse value was arbitrarily chosen as 1. Error bars indicate ±SD. Statistical analysis was by unpaired, two-tail Student's t test. *p<0.05, **p<0.01.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "A: MEFs from Pitrm1+/+, Pitrm1+/-, Mfn1-/-, Mfn2-/-, as well as h-PITRM1 R183Q and h- PITRM1 WT were exposed to Aβ1-40 peptide for 18h. Note that Aβ1-40 signal was still evident in Pitrm1+/- and h-PITRM1 R183Q cells.B: quantification of three independent experiments similar to those shown in panel A. Statistical analysis was by unpaired, two-tail Student's t test. **p<0.01, ***p<0.001.",
    "ncbi_link": "Aβ: 351
Mfn1: 67414
Mfn2: 170731
PITRM1: 10531
Pitrm1: 69617"
  },
  {
    "caption": "(C) Fluorescence polarization assays demonstrating that a peptide containing the BH3‐like domain of Beclin‐1 interacts with Bcl‐XL. Recombinant Bcl‐XL ΔTM was incubated with carboxyfluorescein‐labeled Bak BH3 peptide, in the absence or presence of wild‐type (WT) Beclin‐1 BH3 or either of the two mutant peptides described in B.",
    "ncbi_link": "Bcl‐XL: 598"
  },
  {
    "caption": "(D) Affinity determination of the interaction between recombinant Bcl‐XLΔTM and fluorescent Beclin‐1 BH3, by fluorescence polarization. A comparison between WT Bcl‐XL(squares) and G138A Bcl‐XL (triangles) is shown (means±s.d., n=3 separate experiments).",
    "ncbi_link": "Bcl‐XL: 598"
  },
  {
    "caption": "(E) Co‐immunoprecipitation of Bcl‐XL and WT or mutant Beclin‐1. HeLa cells were transfected with the indicated constructs, followed by immunoprecipitation of Flag‐tagged Bcl‐XL and immunochemical detection of Beclin‐1.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(F) Co‐immunoprecipitation of Beclin‐1 with‐WT and mutant (G138A) Bcl‐XL. Results are representative of at least three experiments yielding similar results.",
    "ncbi_link": "Bcl‐XL: 598"
  },
  {
    "caption": "(A) Competition between Beclin‐1 BH3 and ABT737 for Bcl‐XL binding. A fluorescent 25‐mer peptide containing the BH3‐like domain of Beclin‐1 ( Figure 1D) was docked to recombinant Bcl‐XL ΔTM protein in the absence or presence of ABT737. The IC50 of ABT737, as measured in the presence of 15 nM of peptide and 100 nM of Bcl‐XL ΔTM, was 1.7 μM.",
    "ncbi_link": "Bcl‐XL: 598"
  },
  {
    "caption": "(A, B) Detection of autophagic vacuoles by LC3‐GFP and their modulation by ABT737 and by Beclin‐1‐specific siRNAs. HeLa cells were transfected with control or Beclin‐1‐specific siRNAs, 24 h later re‐transfected with LC3‐GFP, cultured in complete medium (CM) for 24 h, and finally kept 12 h either in CM or in nutrient‐free (NF) conditions, in the presence or absence of 1 μM ABT737. Representative microphotographs of cells cultured in NF medium are shown in (A) and the percentage (means±s.d., n=3 separate experiments) of LC3‐GFP‐transfected cells bearing LC3‐GFP aggregates in the cytoplasm (LC3‐GFPvac) are quantified in (B). The insert in (B) demonstrates the efficiency of the Beclin‐1‐specific siRNAs, as quantified by immunoblot.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(C, D) Detection of cytoplasmicvacuoles using chloromethylfluorescein diacetate (CMFDA). Cells were transfected with control or Beclin‐1‐specific siRNAs, cultured for 48 h in CM, washed, cultured in CM (D) or NF (C, D) for 12 h, stained with CMFDA, and either photographed (C) or subjected to the quantification of the cells that bear at least one discernible cytoplasmicvacuole (arrow head) (means±s.d., n=3 separate experiments).",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "Quantification of autophagic vacuoles induced by ABT737. HeLa cells transfected with the indicated siRNAs (specific for Emerin or for Beclin‐1 at 0 h) were re‐transfected with LC3‐GFP finally cultured in nutrient‐free (NF) conditions (60-72 h), in the presence or absence 1 μM ABT737 and then subjected to electron microscopy detection of immature (AV1) or mature (AV2) autophagic vacuoles. Representative pictures are shown in (A).",
    "ncbi_link": "Beclin‐1: 8678
Emerin: 2010
LC3: 440738///81631///84557"
  },
  {
    "caption": "(A-D) Modulation of Beclin‐1‐induced autophagy by BH3 mutants and ABT737. Cells were transfected with GFP‐LC3 together with an empty control vector or Beclin‐1 (WT, L116A, F123A) and cultured for 48 h, followed by overnight culture in CM (B) or NF (A, B) in the absence or presence of 1 μM ABT737. Representative microphotographs are shown in (A) and the LC3‐GFP‐positive vacuoles per cell are quantified in (B) (means±s.d.; n=3 separate experiments). Alternatively, cells were not transfected and stained with CMFDA to detect vacuoles, as shown in (C) and (D), yielding similar results as for the LC3‐GFP method.",
    "ncbi_link": "Beclin‐1: 8678
LC3: 440738///81631///84557"
  },
  {
    "caption": "(E) BH3‐dependent modulation of Beclin‐1‐induced autophagy by anti‐apoptotic Bcl‐2 proteins. Cells were transfected simultaneously with Beclin‐1 (or control vector) and equivalent amounts of plasmids coding for WT Bcl‐XL, Bcl‐XL G138A, Bcl‐2 or Mcl‐1 (or control vector), as well as GFP‐LC3. The culture in CM or NF in the absence or presence of ABT737 was performed during the last 12 h of the 60 h‐long experiment. The percentage of cells exhibiting the accumulation of LC3‐GFP in vacuoles (LC3‐GFPvac) is quantified as means±s.d. (n=3 separate experiments).",
    "ncbi_link": "Bcl‐2: 596
Bcl‐XL: 598
Beclin‐1: 8678
Mcl‐1: 4170"
  },
  {
    "caption": "(B) Immunoprecipitation of wild‐type and ER‐targeted Bcl‐2 with Beclin‐1. Cells stably transfected with wild type, ER‐ and mitochondrion‐targeted Bcl‐2 were subjected to starvation or treated with ABT737, followed by immunoprecipitation of Bcl‐2 and immunodetection of Beclin‐1.",
    "ncbi_link": "Bcl‐2: 596"
  },
  {
    "caption": "(D, E) Impact of Bad depletion on autophagy. Cells were transfected with LC3‐GFP together with siRNAs specific for Bad, siRNAs specific for emerin or the Beclin‐1‐associated PI3 kinase Vps34. Forty‐eight hours later, when the siRNAs had down‐regulated the proteins of interest (D), cells were subjected by nutrient depletion (NF) or addition of rapamycin (E) and the frequency of cells exhibiting LC3‐GFP aggregation as a marker of autophagy was assessed after 18 h (means±s.d., *P0.05, n=3 separate experiments).",
    "ncbi_link": "Bad: 572
emerin: 2010
Vps34: 5289"
  },
  {
    "caption": "(F) Effect of the Bad knock‐out on autophagy. Wild Type (WT) or Bad−/− MEF were transfected with LC3‐GFP and then subjected to nutrient depletion (NF) and/or treatment with ABT737 (18h; means±s.d., n=3). The asterisks denotes a significant (P0.05) effect of Bad deficiency.",
    "ncbi_link": "Bad: 12015"
  },
  {
    "caption": "(G) Effect of the Bad knockout on the Beclin‐1/Bcl‐2 interaction. WT or Bad−/− MEF were subjected to the indicated treatments, followed by immunoprecipitation of Bcl‐2 and immunobloting of Beclin‐1.",
    "ncbi_link": "Bad: 12015"
  },
  {
    "caption": "(H) Overexpression of Bad triggers autophagy. Cells were transfected with LC3‐GFP alone (Control), together with vector‐only or with a vector encoding Bad, and subjected 48 h later to nutrient depletion (NF). Cells were cultured in the continuous presence or absence of the pan‐caspase inhibitor Z‐VAD‐fmk (50 μM) for 16 h, followed by assessment of autophagy as in (E) (means±s.d., n=3 separate experiments, *P0.01). Immunoblots are representative of at least three independent experiments.",
    "ncbi_link": "Bad: 12015"
  },
  {
    "caption": "(A) Representative images of wt and egl‐1 mutant embryos, bearing the plgg−1DsRED",
    "ncbi_link": "egl‐1: 179943"
  },
  {
    "caption": "D Representative confocal  images of HEK293  cells expressing various GFP-fused proteins (green) and supplemented with TopFluor® TMR-PS (red); scale bar = 10 µm. Yellow arrows indicate high intensity PS  fluorescent regions. E %PM  with PS  clusters = area of high intensity fluorescent PS  clusters over total  plasma membrane area from images in panel D. Black bars are control proteins and blue bars are eVP40    proteins. Values are reported as mean ± s.d.; N>18 cells per biological replicate, n=3 for 3 biological replicates; A one-way ANOVA was performed with multiple comparisons compared to the control GFP  %PS  clustering (***p=0.0007, **p=0.004). Data information: PS: phosphatidylserine; PM: plasma membrane.",
    "ncbi_link": "GFP: 
VP40: 911825"
  },
  {
    "caption": "D, E PS  concentration in LUVs  enhances the ability of His6-eVP40  to oligomerize on membranes. D Representative western blot of chemical crosslinking performed on His6-WT-eVP40   following incubation with LUVs  of varying PS  content (detected by Mouse α-His  antibody & HRP-Sheep α-Mouse). E Oligomerization  capacity was determined from the western blot  band density ratio of oligomers/(monomer + dimer) from chemical crosslinking experiments. A one-way ANOVA was performed with multiple comparisons compared to the control 0% PS LUVs  control (30% PS  *p= 0.02; 60% PS  *p=0.017). n=3 biological replicates. Values are reported as mean ± s.d.; Data information: LUVs:  large unilamellar vesicles; PS: phosphatidylserine; HRP: horseradish peroxidase.",
    "ncbi_link": "His: 
VP40: 911825"
  },
  {
    "caption": "D, E Analysis of PS  clustering in HEK293  cells in response to fendiline  treatment through N&B analysis. D Left panel: Representative images from  time-lapse  (30 frames) imaging of HEK293  expressing GFP-LactC2  and treated with fendiline  for 48 hours; scale bar= 5 µm. Middle panel: Brightness and Intensity plots for each representative image. Right panel: Selection map correlating each pixel in the representative image to an oligomerization  state (b value) (red: monomer-5mer, green: 5mer-10mer, blue: >10mer). E Average % pixels quantification from panel (d)= Percentage of GFP-LactC2  with brightness values corresponding to monomer-5mer (~1.-1.5), 5mer-10mer (~1.5-1.9) and >10mer (>1.9) over the total pixels within each image. Values are reported as mean ± s.d.; N≥9, n=3 biological replicates; A two-way ANOVA was performed with Dunnett's multiple comparisons comparted to the control DMSO  % average pixels (****p<0.0001, **p=0.0043). Data information: GFP-LactC2: phosphatidylserine  sensor; N&B:  Number & Brightness analysis; PS: phosphatidylserine.",
    "ncbi_link": "GFP: 
LactC2: 281913"
  },
  {
    "caption": "A-C Effect of fendiline  on eVP40  and mVP40 PM localization  in HEK293  cells after 48 hours of treatment. A Representative confocal  images from live cell imaging  experiments of HEK293  cells expressing EGFP-WT-eVP40 (top panel) and EGFP-WT-mVP40   (bottom panel) after 48 hours of fendiline  treatment. scale bars= 10 µm. Effect of fendiline  on mVP40 (B) and eVP40 (C) PM localization  was quantified by the ratio of EGFP  fluorescence intensity at the PM / total EGFP  fluorescence intensity (and normalized to DMSO  control). N>15 cell per biological replicate, n=3 biological replicates. Values are reported as mean ± s.d. A one-way ANOVA with multiple comparisons was performed compared to the DMSO  control. Data information: PM: plasma membrane",
    "ncbi_link": "EGFP: 
VP40: 911825
VP40: 920947"
  },
  {
    "caption": "D, E Analysis of eVP40 oligomerization  in HEK293  cells in response to 48 hour fendiline  treatment using N&B analysis. D Left panel: Representative images from  time-lapse  (30 frames) of HEK293  expressing EGFP-WT-eVP40 and treated with fendiline  for 48 hours. scale bar = 5 µm. Middle panel: Brightness and Intensity plots for each representative image. Right panel: Selection map correlating each pixel in the representative image to an oligomerization  state (b value) (red: monomer-hexamer, green: hexamer-12mer, blue: 12mer-24mer, pink: >24mer). E Average % pixel quantification from panel (d)= % of GFP-WT-eVP40 with brightness values corresponding to monomer-hexamer (~1.-1.6), hexamer-12mer (~1.6-2.0), 12mer-24mer (2.0-3.2) and >24mer (>3.2) over the total pixels within each image. Values are reported as mean ± s.d.; N≥9 cell per biological replicate, n=3 biological replicates; A two-way ANOVA was performed with Dunnett's multiple comparisons compared to the control DMSO  % average pixels (**p=0.0035). Data information: N&B: Number & Brightness analysis.",
    "ncbi_link": "EGFP: 
VP40: 911825"
  },
  {
    "caption": "A-C TEM  analysis of eVLP morphology. A Representative transmission electron micrographs  of eVLPs  purified from HEK293  cells expressing FLAG-eVP40 and eGP following 48 hours of DMSO  (left panel) or 5 µM fendiline  treatment (right panel). B Quantification of eVLP  length (µm) of DMSO-derived eVLPs  (black) and fendiline-derived eVLPs  (blue). N>50 VLPs   per biological replicate, n=3 biological replicates. Values are reported as mean ± s.d. A two-tailed t-test was performed (**p=0.0139). C Quantification of eVLP   diameter (nm) of DMSO-derived eVLPs  (black) and fendiline-derived eVLPs  (blue). N>50 VLPs   per biological replicate, n=3 biological replicates. Values are reported as mean ± s.d. A two-tailed t-test was performed (*p=0.0430). Data information: TEM: transmission electron microscopy; eVLPs: entry-competent VLPs; eGP: Ebola virus glycoprotein",
    "ncbi_link": "FLAG: 
glycoprotein: 
GP: 
VP40: 911825"
  },
  {
    "caption": "(A) Levels of BRCA1 promoter hypermethylation, levels BRCA1 mRNA and the presence of BRCA1 nuclear foci by immunofluorescence are shown T127 and T162 were used as positive controls for hypermethylated BRCA1 promoter. Error bars indicate SEM from independent tumors (n ≥ 2). Dashed line indicates mean of BRCA1 mRNA levels in normal breast. PARPi-response is shown in the summary underneath: white box: PD; black box: PR/CR. Alterations in HRR-related genes in PDX are also indicated.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(B) Western blot of PALB2 detected in U2OS cells and PDXs. Three biological replicates of PDX093 are shown; PDX302 is used as PALB2 wild type PDX control.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "(C) YFP-PALB2 recruitment to laser-induced DSBs is impaired in HeLa cells expressing PALB2 p.M296Nfs (n=4, unpaired t-test at 16min).",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "Gene-targeting efficiency using Cas9/mClover-LMNA1 homologous recombination assay of (D) siRNA PALB2 cells (n=4, one-way ANOVA) or (E) cells with no PALB2 depletion complemented with wild type and p.M296Nfs siRNA-resistant constructs (n=7, one-way ANOVA). Western blots of PALB2 wild type and PALB2 p.M296Nfs for each condition are shown. Error bars indicate SEM from independent experiments.",
    "ncbi_link": "mClover: 
LMNA1: 4000
PALB2: 79728
Cas9: 901176"
  },
  {
    "caption": "(A) Percentage of geminin-positive, RAD51 nuclear foci-containing cells detected by immunofluorescence in FFPE samples from PDX tumors treated with vehicle or PARPi Error bars indicate SEM from independent tumors (n ≥ 2). PARPi-response is shown in the summary underneath: white box: PD; black box: PR/CR. Immunofluorescence staining of RAD51 foci in PARPi- and vehicle-treated PDX tumors is shown. Alterations in HRR-related genes are also summarized: hBRCA1: BRCA1 promoter hypermethylation and lack of BRCA1 expression and BRCA1 nuclear foci formation.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(C) Immunofluorescence staining of 53BP1 and BRCA1 nuclear foci [with an antibody towards the N-terminus (B1-NT) or C-terminus (B1-CT) of BRCA1] in three BRCA1-mutant, PARPi-resistant models from PDX cohort-2. The location of the mutation within the gene is indicated. Scale bars: 10µm.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(B) Percentage of geminin-positive, RAD51 or γH2AX nuclear foci-containing cells in FFPE tumor samples from patients with HBOC syndrome. The box underneath summarizes the patient's young onset (<35y: <35 years), her family history (FH, purple box for PALB2-related tumors) and the presence of BRCA1 nuclear foci in the analyzed tumor samples.",
    "ncbi_link": "PALB2: 79728"
  },
  {
    "caption": "(C) Immunofluorescence staining of γH2AX, BRCA1 and RAD51 foci in three representative FFPE tumors from patients: one RAD51- and BRCA1-positive tumor (Pt03), one RAD51- and BRCA1-negative tumor (Pt11) and one PALB2-related tumor, with BRCA1 but not RAD51 nuclear foci (Pt20.1). Scale bars: 10µm.",
    "ncbi_link": "BRCA1: 672
PALB2: 79728
RAD51: 5888"
  },
  {
    "caption": "A Immunoblot analysis with the indicated antibodies of immunoprecipitates (IP) prepared from the SSU fraction of eIF3D-V5/eIF4E-FLAG dKI HEK293T cells (eIF3D/4E dKI) or wild-type (WT) cells with antibodies to the epitope tags. The SSU fraction (input) was also analyzed directly. Cells were fixed with formalin, cell lysates were treated with RNase, and the SSU and RS fractions were separated by sucrose density gradient centrifugation before immunopurification. Molecular sizes are indicated in kilodaltons.",
    "ncbi_link": "FLAG: 
V5: 
eIF3D: 8664
4E: 1977
eIF4E: 1977"
  },
  {
    "caption": "B, C Immunoblot analysis with the indicated antibodies of immunoprecipitates prepared as in A from the SSU fraction of eIF4A1-FLAG KI HEK293T cells (eIF4A1 KI) (B) or ASCC3-FLAG KI HEK293T cells (ASCC3 KI) (C).",
    "ncbi_link": "FLAG: 
ASCC3: 10973
eIF4A1: 1973"
  },
  {
    "caption": "Immunoblot analysis with the indicated antibodies of immunoprecipitates prepared as in A from the RS fraction of RPL7A-HA KI HEK293T cells (RPL7A KI) (F).",
    "ncbi_link": "HA: 
RPL7A: 6130"
  },
  {
    "caption": "A RNA-seq results for eIF4A1, eIF4A2, ASCC2, and ASCC3 in HEK293T cells transfected with siRNAs specific for eIF4A1 and eIF4A2 (eIF4A1/A2 dKD #1 or #2) or for ASCC3 (ASCC3 KD #1 or #2) relative to cells transfected with a control siRNA. The dashed line indicates a fold change of 1.",
    "ncbi_link": "ASCC2: 84164
ASCC3: 10973
eIF4A1: 1973
A2: 1974
eIF4A2: 1974"
  },
  {
    "caption": "Volcano plots for differential TE (D) The changes in TE and SRO for eIF4A1/A2 dKD #1 and #2 and for ASCC3 KD #1 and #2 HEK293T cells compared with control cells were analyzed with RiboDiff. The gray dashed lines indicate an adjusted P value of 0.05. P values were calculated by chi-square test and adjusted by Benjamini-Hochberg method.",
    "ncbi_link": "ASCC3: 10973
eIF4A1: 1973
A2: 1974"
  },
  {
    "caption": "D, E Cumulative fraction for fold change in TE in eIF4A1/A2 dKD or ASCC3 KD cells relative to control cells. Results are shown for all coding transcripts and for transcripts with a decreased (D) or increased (E) SRO. The P values were calculated with the Mann-Whitney U test.",
    "ncbi_link": "ASCC3: 10973
eIF4A1: 1973
A2: 1974"
  },
  {
    "caption": "D Cumulative fraction for fold change in TE in eIF4A1/A2 dKD or ASCC3 KD cells relative to control cells. Results are shown for all coding transcripts and skewed transcripts. The P values were calculated with the Mann-Whitney U test.",
    "ncbi_link": "ASCC3: 10973
eIF4A1: 1973
A2: 1974"
  },
  {
    "caption": "E Number of transcripts showing significant down-regulation of TE among skewed transcripts in eIF4A1/A2 dKD and ASCC3 KD cells.",
    "ncbi_link": "ASCC3: 10973
eIF4A1: 1973
A2: 1974"
  },
  {
    "caption": "Luciferase assays for RADX, DNAJB6, and LDHA constructs (B) in control and ASCC3-depleted HEK293T cells. The results of the luciferase assays (right) and schematic representations of the constructs (left) are shown. Rluc, Renilla luciferase; Fluc, firefly luciferase. Assay data are means ± s.d. for three independent experiments. *P < 0.05, **P < 0.01, *** P < 0.001, NS (two-sided Student's t test).",
    "ncbi_link": "Fluc: 
luciferase: 
Rluc: 
ASCC3: 10973
DNAJB6: 10049
LDHA: 3939
RADX: 55086"
  },
  {
    "caption": "Luciferase assays for corresponding deletion mutants of the RADX and DNAJB6 constructs (C) in control and ASCC3-depleted HEK293T cells. The results of the luciferase assays (right) and schematic representations of the constructs (left) are shown. The deleted regions of the RADX and DNAJB6 constructs are indicated by dashed white boxes. Rluc, Renilla luciferase; Fluc, firefly luciferase. Assay data are means ± s.d. for three independent experiments. *P < 0.05, **P < 0.01, *** P < 0.001",
    "ncbi_link": "Fluc: 
luciferase: 
Rluc: 
ASCC3: 10973
DNAJB6: 10049
RADX: 55086"
  },
  {
    "caption": "C Similar to CSR-1, the majority of small RNAs interacting with CSR-2 in vivo have 5′PPP ends. The RNAs in the immunopurified Argonaute complexes were treated with or without Vaccinia virus capping enzyme followed by an alkaline phosphatase, and finally labeled with [γ-32P]ATP and a polynucleotide kinase. RNA products were resolved by 15% sequencing gels.",
    "ncbi_link": "CSR-2: 
CSR-1: 177591"
  },
  {
    "caption": "G Three csr-1 hypomorphic mutants showed a diminished RNAi response to exo-dsRNA. The WT, the csr-1(fj150) mutant, and several strains were injected with dsRNA (1.25 µg/µL) targeting the maternal gene pos-1, essential for embryogenesis. The incidence of lethal embryos in the F1 progeny was examined. The number of F1 progeny counted is indicated by n. Error bars represent 95% confidence intervals (CIs).",
    "ncbi_link": "csr-1: 177591
pos-1: 179224"
  },
  {
    "caption": "E Immunofluorescence images of H3K9me2 and SYP-1 in male nuclei of the WT and the Argonaute mutants. High-resolution fluorescence images, 3D reconstruction images (3D CG), and maximum intensity projection (MIP) images of segmented H3K9me2 signals are presented. In the male nuclei of the csr-1 mutant and the csr-2; csr-1 double mutant, some H3K9me2 segments showed abnormally large volumes (narrow arrow) and/or overlapped partially with SYP-1 signals (arrowhead). In the double mutant, DAPI signals were often detected in an aggregated state (dashed line).",
    "ncbi_link": "csr-2: 
csr-1: 177591"
  },
  {
    "caption": "Immunofluorescence experiments were performed on the pachytene nuclei of X0 males. C H3K9me2 signals at the pachytene region in the males of cec mutants and cohesin mutants. Worms were cultured at 20°C, except for the smc-1(e870) mutant that was cultured at 23°C. The intensity of the H3K9me2 signal in the him-8 mutant male was similar to that in the WT male.",
    "ncbi_link": "smc-1: 172116
him-8: 188247"
  },
  {
    "caption": "C SC formation in the WT and multiple mutants were analyzed by immunostaining against SYP-1 and COH-3/4. The SC formed string-like structures in the csr-2; csr-1 double mutant and the ego-1 mutant, but the superstructure of the SC was often abnormally branched.",
    "ncbi_link": "csr-2: 
csr-1: 177591
ego-1: 172524"
  },
  {
    "caption": "A Multicolor FISH for the 5S rRNA region (rDNA, green) of autosome V and the right region of the X chromosome (LGX-R, magenta) in nuclei of the WT strain, coh-3/4 double mutant, csr-1 mutants, csr-2; csr-1 double mutant, and ego-1 mutant. Arrows indicate occasional colocalizations of the 5S rDNA and X-R loci detected in the mutant strains.",
    "ncbi_link": "csr-2: 
coh-3: 179949
csr-1: 177591
ego-1: 172524"
  },
  {
    "caption": "E csr-1(fj67) and csr-1(fj126) in-frame mutations reduced the abundance of CSR-1 at the chromosomal regions in pachytene nuclei. The WT strain and the csr-1 mutants were stained by anti-CSR-1 antibodies.",
    "ncbi_link": "csr-1: 177591"
  },
  {
    "caption": "A, B ChIP-seq data for CSR-1, SMC-1, COH-3/4, and histone H3K9me2 were compared with sub-populations in CSR-1-interacting small RNAs. Adult worms were used for experiments. ChIP signals on autosome III (A) and the X chromosome (B) from the WT hermaphrodites were visualized by aggregation plots with a bin size of 20 kbp. H3K9me2 ChIP signals derived from the him-8 mutant population rich in X0 males are shown in the lower part. The common ChIP regions computed from the technical duplicates were used for panels A, B, In the adult body, about half of the nuclei correspond to germ cells. Most H3K9me2 ChIP signals from the WT hermaphrodites were likely to originate in somatic cells because staining signals of H3K9me2 in adult hermaphrodites were detected abundantly in somatic cells and very weakly in the germline. Most meiosis-specific COH-3/4 ChIP signals were thought to originate in the germline. For comparison, aggregation plots were also constructed from the following sub-populations of CSR-1-interacting small RNAs: small RNAs mapped in sense orientation to coding genes (exons and introns), and repeat-derived small RNAs. The small RNA data merged from the technical duplicates were used for panels A and B. Densities of protein-coding exons, all non-simple repeats, and five major repeats on the reference genome are attached. The CeRep55 sequences were partially degenerate, and no clear ChIP signal for CSR-1 was detected in CeRep55 cluster #4 on the X chromosome in the ce10 reference genome.",
    "ncbi_link": "him-8: 188247"
  },
  {
    "caption": "F The CeRep55 lncRNA signals partially colocalized with those of COH-3/4 in hermaphrodites. Pachytene nuclei in the WT strain and the csr-2; csr-1 double mutant were stained.",
    "ncbi_link": "csr-2: 
 csr-1: 177591"
  },
  {
    "caption": "H The CeRep55 lncRNA signal was also detected at a region of the unpaired X chromosome where the CEC-5 and COH-3/4 signals overlapped. The pachytene chromosome showing the strongest CEC-5 enrichment was considered to be the unpaired X chromosome in males. The RNA-directed in situ hybridizations were performed with stringent conditions that detected only long RNAs.",
    "ncbi_link": "CEC-5: 177537
COH-3: 179949"
  },
  {
    "caption": "Pachytene nuclei were analyzed. B Multicolor FISH using the 5S rDNA and LGX-R probes in the csr-1(fj150) mutant and the csr-1(fj150); CeRep55_X(Q) mutant.",
    "ncbi_link": "csr-1: 177591"
  },
  {
    "caption": "(Ci) The levels of WDR6 were determined and normalized against GAPDH in three groups. Normal, n=21; Noninvasive, n=15; Invasive, n=8. (Cii) The levels of WDR6 in 10 pairs of patients' tissues.",
    "ncbi_link": "GAPDH: 2597
WDR6: 11180"
  },
  {
    "caption": "(F) Analysis of WDR6 using TCGA LIHC data. Fi and Fiii were plotted with GEPIA analyzing tool, and Fii were analyzed by UALCAN analyzing tool.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(A) Western blots confirmed WDR6 knockdown in HCC cells transduced with shWDR6 or shcontrol lentiviral vector.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(B) The effects of WDR6 silencing on the invasive and proliferative ability of HCC cells, respectively. Left panel: HCC-LM3: P=0.912 shControl vs shWDR6-#1, P=0.889 shControl vs shWDR6-#2; HepG2: P=0.826 shControl vs shWDR6-#1, P=0.796 shControl vs shWDR6-#2; right panel: HCC-LM3: P=0.856 shControl vs shWDR6-#1, P=0.814 shControl vs shWDR6-#2; HepG2: P=0.726 shControl vs shWDR6-#1, P=0.745 shControl vs shWDR6-#2.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(C) The survival plot of Albumin-Cre/+; Wdr6f/f mice with DEN-induced HCC.",
    "ncbi_link": "Wdr6: 
Albumin: 11657
Cre: 2777477"
  },
  {
    "caption": "(F) Flow cytometric analysis of MDSC and T cells in tumors from BALB/c mice with H22-WDR6 or empty vector cells orthotopically implantation (n=6/group).",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(G) α-Gr1 antibody injection markedly decreased the tumor volume and lung metastatic nodules' number in BALB/c mice with H22-WDR6 cells orthotopically implantation when compared to IgG control (n=5/group).",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(Ai) ATAC-sequencing showed the effects of WDR6 knockdown on the chromatin accessibility of IL10, IL1β, IL6, and TNFα loci. (Aii) quantitative real-time polymerase chain reaction (qRT-PCR) analyzing cytokines' mRNA levels in Hepa1-6 and H22 cells treated with or without shWDR6 or WDR6, respectively.",
    "ncbi_link": "IL10: 16153
IL1β: 16176
IL6: 16193
TNFα: 21926
WDR6: 83669"
  },
  {
    "caption": "(B) TNFα ELISA assays were performed in the conditioned medium from Hepa1-6 and H22 cells with WDR6 knockdown or overexpression, respectively.",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(D) The effects of TNFα knockdown in H22-WDR6 cells on MDSC recruitment (Dii), tumor size (Diii), and the ratio of IFN-γ+ CD8+ T cells (Div) in tumors from syngeneic mice (n=5/group).",
    "ncbi_link": "TNFα: 21926
WDR6: 83669"
  },
  {
    "caption": "(E) TNFα supplementation decreased MDSC infiltration induced by WDR6 knockdown in tumor tissues from syngeneic mice (n=6/group).",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(A) The effects of NF‐κB inhibitor IMD0354 or IκBα‐SR on TNFα expression in MHCC-97L cells with or without WDR6 overexpression.",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(B) The effects of WDR6 knockdown on the protein levels of p65, RelB, c-Rel, p52, and p50 in HCC cells.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(Di-ii) The effects of autophagic deficiency using 3-MA on the levels of p65 protein and TNFα secretion in HCC cells with WDR6 knockdown.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(Ei) WDR6 mRNA levels in Hep3B and MHCC-97L cells treated with or without TNFα in culture media. (Eii) Schematic diagram showing three candidate NF‐κB-binding sites in WDR6 promoter. (Eiii) The impact of IMD0354 on the luciferase reporter of WDR6 proximal promoter in HCC cells. (Eiv-v) ChIP assays using HCC cells or HCC tissues from patients (P#36 and P#54). Da",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(C) Co-IP analysis indicated the effect of WDR6 mutant (R123A) or (R203A) on the binding of CUL4A to endogenous UVRAG in MHCC-97L cells.",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(Di) UVRAG ubiquitination assay in MHCC-97L cells expressing WT-WDR6 or its mutant WDR6-R123A. (Dii) UVRAG ubiquitination in HCC-LM3 cells treated as shown.",
    "ncbi_link": "WDR6: 11180
WDR6: 83669"
  },
  {
    "caption": "(Ei) MS assay identified K176 of UVRAG as major ubiquitination site. (Eii) K176R mutant abolished UVRAG ubiquitination promoted by WDR6.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(A) WDR6 or its mutant (Ai) or WDR6 shRNAs (Aii) or WDR6 with CUL4A siRNA (Aiii) affected the levels of endogenous UVRAG in HCC cell lines.",
    "ncbi_link": "CUL4A: 8451
WDR6: 83669
WDR6: 11180"
  },
  {
    "caption": "(B) CHX assays of UVRAG stability in HCC-LM3 cells transfected with WDR6 shRNA.",
    "ncbi_link": "WDR6: 11180"
  },
  {
    "caption": "(C) The effects of WT-WDR6 or WDR6-R123A mutant on UVRAG levels in MHCC-97L cells in the presence of MG132.",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(Di-iii) UVRAG knockdown in Hepa1-6 cells reverted WDR6-deficient-induced chromatin accessibility of TNFα locus and TNFα secretion in culture medium. The cells in (Di) were orthotopically implanted into C57BL/6J mice.",
    "ncbi_link": "TNFα: 21926
UVRAG: 78610
WDR6: 83669"
  },
  {
    "caption": "(F) Heat-map showing the expression of altered genes related to functional signatures in MDSCs after WDR6 alone or with UVRAG knockdown.",
    "ncbi_link": "UVRAG: 78610
WDR6: 83669"
  },
  {
    "caption": "(C) BALB/c mice introduced with H22-WDR6 overexpression cells were administered with Pep2-WDxR or Pep2-con with or without anti-PD-L1 antibody. The images and sizes of HCC (Ci), hematoxylin-eosin (H&E) staining and metastasis nodules of lung were presented (Cii). The survival analysis of the mouse after treatment was performed (n = 9/group) (Ciii). In the BALB/c mice from (C), Flow cytometry was performed to analyze PMN-MDSC, M-MDSC, and IFN-γ+ CD8+ T cells in tumors (Civ).",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "(D) The survival test of DEN- and CCl4-induced HCC using WDR6-knockout and WT mice. At twenty-six weeks, mice were administered with or without anti-PD-L1 antibody (n = 6/group).",
    "ncbi_link": "WDR6: 83669"
  },
  {
    "caption": "A,B. 3D views (A) and quantification of variations in the mean tumor volume (B) of HH25 chick embryos engrafted with BRAFwt (OF-MEL-028) or BRAFV600E (OF-MEL-020, OF-MEL-027) patient samples and treated with excipient or a combination of Vemurafenib and Cobimetinib. The number of embryos analyzed for each patient sample is indicated on the graphs. Student t-test for OF-MEL-020; Mann-Whintey test for OF-MEL-028, *: p < 0.05, ns: not significant. Exact p-values are indicated on the graphs.",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "Western blot analysis of whole cell lysates from HEK 293 WT and NEDP1 KO cells reveals a loss of free NEDD8 (indicated by asterisk) and an accumulation of NEDD8 reactive species in the NEDP1 KO lysate. The predicted molecular weight sizes of putative, unanchored, poly-NEDD8 chains are denoted by N2 through to N5. Unconjugated NEDD8 is denoted by N1.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDD8 affinity resin shows enrichment of endogenous neddylated proteins in WT and NEDP1 KO cells. Recombinant HALO-NEDP1 C163A (CA) conjugated to HALO-Link beads was used as an affinity resin to enrich for neddylated proteins in lysates from HEK 293 WT and NEDP1 KO cells. Enriched proteins were resolved by SDS-PAGE and processed for Western blot analysis with NEDD8 or Ubiquitin antibodies. HALO-NEDP1 CA specifically enriches for NEDD8-reactive proteins in both WT and NEDP1 KO cells, but does not enrich for Ubiquitin-modified proteins in either cell line.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Components of the NEDD8 conjugation machinery are enriched in HALO-NEDP1 pulldowns from NEDP1 KO lysates. Neddylated proteins from HEK293 KO cells were enriched by HALO-NEDP1 CA pulldown, as in (B) but not by the NEDD8 nonbinder mutant, HALO-NEDP1 DAGC (D29W A98K G99K C163A). The NEDD8 E1s, UBA3 and ULA1, are modified in NEDP1 KO cells, as well as E2 UBE2M, and co-E3s DCNL1 and DCNL2. Cul2 and Cul3 are hyper-neddylated in NEDP1 KO cells. CSN components, CSN5 and CSN8, also co-precipitate in HALO-NEDP1 CA pulldowns.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Western blot analysis from HEK 293 WT and NEDP1 KO cells of the components of the NEDD8 conjugation/de-conjugation pathway shows that similar levels of NEDD8 pathway components are present in both WT and NEDP1 KO cells. Apart from UBA3, there is no detectable amount of NEDD8-modified enzymes in whole-cell lysates from NEDP1 KO cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Neddylated species are NEDD8 E1 dependent. WT and NEDP1 KO HEK 293 cells were treated with NAE inhibitor MLN4924 at 3 μM for the indicated time. Lysed cells were then processed for Western blot analysis. NEDD8 E1 inhibition results in a time-dependent decrease in the amount of Cullin and non-Cullin NEDD8 reactive bands.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Neddylated species are UBE2M dependent. WT and NEDP1 KO HEK 293 cells were left untreated or treated with the indicated siRNA for 48 hours. Lysed cells were then processed for Western blot analysis. Neddylated species are reduced when NEDD8 E2 UBE2M was depleted after siRNA treatment (si2M), but not with control siRNA (siCTRL) or when NEDD8 E2 UBE2F was depleted (si2F). The double knockdown (si2M/2F) does not further reduce NEDD8 modified proteins.",
    "ncbi_link": "NEDP1: 123228
UBE2F: 140739
UBE2M: 9040"
  },
  {
    "caption": "(Left) Western blot analysis of large scale HALO-NEDP1 pulldowns from HEK 293 NEDP1 KO lysates. (Right) Diagram of mass spectrometry sample preparation.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Scatterplot of proteins identified by mass spectrometry analysis identifies NEDD8 and components of the NEDD8 conjugation pathway as being the most abundant proteins in HEK 293 NEDP1 KO lysates following NEDP1-CA pulldown. iBAQ analysis of proteins identified in A) are plotted as the log2 value of the enrichment ratio (mass spectrometry intensity of the HALO-NEDP1 CA pulldown over HALO-NEDP1 DAGC pulldown) versus the log10 value of the iBAQ intensity from the HALO-NEDP1 CA pulldown. Blue markers indicate known components of the NEDD8 pathway and red markers indicate proteins that have been identified as substrates of PARP-1 in the database of ADP-ribosylated proteins, ADPriboDB (Vivelo et al., 2017).",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "(Left) The 25-kDa neddylated species induced by oxidative stress increases with time in WT U2OS cells. U2OS WT or NEDP1 KO cells were treated with 600 μM H2O2 for the indicated time and then lysed in LDS sample loading buffer and processed for Western blot analysis. (Right) The same 25 kDa NEDD8 species, which is strongly induced in WT cells, is present in untreated NEDP1 KO cells and does not further increase after oxidative stress induced by H2O2 (as indicated by the arrow).",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "U2OS NEDP1 KO cells are resistant to the PARP-1 inducer, H2O2. WT and NEDP1 U2OS cells were plated in 96-well plates and after 24 hours were treated with the indicated concentration of H2O2. They were assessed for viability 24 hours later by the CellTiter-Glo assay. Graphs represent the mean ± S.E.M. of the percent survival compared to untreated cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDP1 KO cells are re-sensitized to H2O2, following re-expression of NEDP1 by transient transfection. U2OS cells were plated in 96 well plates and reversed transfected with NEDP1 or an empty vector. 48 hours after plating, cells were challenged with the indicated amount of H2O2 and cell viability was assessed 24 hours later by the CellTiter-Glo assay. Graphs represent the mean ± S.E.M. of the percent survival compared to untreated cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Neddylation of cullins is decreased in NEDP1 KO cells and is rescued by re-expression of NEDP1 by transient transfection. Western blot analysis from HEK 293 WT, NEDP1 KO cells and NEDP1 KO cells rescued with transient transfection of NEDP1 reveals that upon NEDP1 re-expression, the intensity of the NEDD8 reactive bands is reduced and the levels of free NEDD8 are increased. NEDP1 re-expression also increased the neddylation of each Cullin. The neddylated band of each Cullin is denoted with a star. Quantification and graph of the mean ± S.E.M. of the percentage neddylation of each Cullin in (E).",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Deletion of Nedp1 does not lead to induction Nrf2 response genes. RNA was harvested from WT and NEDP1 KO U2OS cells, reversed transcribed to cDNA, and analysed by qPCR for Nrf2 and NQO1 expression.",
    "ncbi_link": "Nrf2: 4780
NQO1: 1728
Nedp1: 123228
NEDP1: 123228"
  },
  {
    "caption": "Deletion of Nedp1 but not of Cand1 in HEK 293 cells results in resistance to cell death from H2O2. WT, NEDP1 KO, and CAND1 KO cells were plated in 96 wells plates and treated with the indicated amount of H2O2. 24 hours after treatment, cell viability was measured using the CellTiter-Glo assay. Graphs represent the mean ± S.E.M. of the percent survival compared to untreated cells.",
    "ncbi_link": "Cand1: 55832
CAND1: 55832
Nedp1: 123228
NEDP1: 123228"
  },
  {
    "caption": "PARP-1 activity is reduced in NEDP1 KO cells. Western blot analysis of whole cell lysates from WT and NEDP1 KO U2OS cells after treatment with 600 μM H2O2 for the indicated amount of time. PAR polymer generation is induced in WT cells after H2O2 treatment but induction is reduced in NEDP1 KO cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "PARP-1 activity is rescued by re-expression of NEDP1 in NEDP1 KO cells. Western blot analysis of whole cell lysates from WT and NEDP1 KO U2OS cells transfected with the indicated constructs. 72 hours after transfection, cells were treated with the indicated amount of H2O2 and processed for Western blot analysis. PAR polymer generation is reduced in NEDP1 KO cells but can be rescued by the transient re-expression of NEDP1.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "PARP-1 inhibitor Olaparib protects WT cells from H2O2 treatment to the same extent as NEDP1 KO. U2OS cells were plated in 96 well plates and 24 hours later pre-treated with Olaparib (10 μM) for 1 hour before treatment with the indicated concentration of H2O2. 24 hours later, cell viability was measured using the CellTiterGlo assay. NEDP1 deletion protects cells from H2O2 treatment to the same extent as PARP-1 inhibition in WT cells. Olaparib does not provide additional protection to NEDP1 cells from H2O2 treatment.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "AIF translocation to the nucleus is impaired in NEDP1 KO cells. WT and NEDP1 KO cells were plated on coverslips and 24 hours later were treated with H2O2 (600 μM) for the indicated amount of time and then processed for immunofluorescence analysis using α-AIF antibodies and DAPI staining. PARP-1 dependent cell death is induced in WT U2OS cells, as indicated by translocation of AIF from the mitochondria to the nucleus (Scale bar 10 μm).",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Total nuclear AIF intensity from (D) was measured with ImageJ and plotted as a vertical scatter plot with the group mean intensity indicated with a black bar. AIF has translocated to the nucleus after WT cells were exposed to H2O2 but not in NEDP1 KO cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDP1 KO cells express normal levels of PARP-1 and AIF. Western blot analysis of whole cell lysates from WT and NEDP1 KO U2OS cells shows that the proteins necessary for the induction of PARP-1 dependent cell death are present at equal levels in both cell lines.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDP1 KO U2OS cells are not resistant to induction of apoptosis from combined treatment with TNF-α and cycloheximide. U2OS cells were plated in 96 well plates and incubated with cycloheximide (10 μg/mL) before addition of the indicated amount of TNF-α. Cell survival was determined 24 hours later using the CellTiter-Glo assay. Graphs represent the mean ± S.E.M. of the percent survival compared to untreated cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDP1 KO U2OS cells are not resistant to treatment with camptothecin (CPT). WT U2OS and NEDP1 KO cells were plated in 96-well plates and treated with the indicated amount of CPT. 48 hours after exposure cell survival was measured using the CellTiterGlo assay. Graphs represent the mean ± S.E.M. of the percent survival compared to untreated cells.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDD8 trimers co-immunoprecipitate with endogenous PARP-1 in NEDP1 KO cells. Lysates were prepared from U2OS NEDP1 KO cells and immunoprecipitation was performed with PARP-1-Trap or GFP-Trap as a negative control. Bound proteins were resolved by SDS-PAGE and processed for Western blot analysis with the indicated antibodies.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "NEDD8 trimers bind to GFP-PARP-1. NEDP1 U2OS KO cells were transfected with GFP or with GFP-PARP-1 and 24 hours later cell lysates were collected. Immunoprecipitation was then performed with GFP-Trap, and bound proteins were resolved by SDS-PAGE and processed for Western blot analysis with the indicated antibodies. GFP-PARP-1 but not GFP alone can co-immunoprecipitate NEDD8 trimers from NEDP1 KO cells.",
    "ncbi_link": "GFP: 
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "NEDD8 trimers bind to GFP-PARP-1. WT or NEDP1 U2OS KO cells were transfected with GFP or with full-length GFP-PARP-1 and 24 hours later treated as indicated with H2O2 (600 μM) for 30 min before cell lysates were collected. Immunoprecipitation was then performed with GFP-Trap, and bound proteins were resolved by SDS-PAGE and processed for Western blot analysis with the indicated antibodies. GFP-PARP-1 but not GFP alone can co-immunoprecipitate NEDD8 trimers from WT cells only after H2O2 treatment or from both treated or untreated NEDP1 KO cells.",
    "ncbi_link": "GFP: 
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "NEDD8 trimers bind to the DNA-binding domain of PARP-1 (Zn1-3) but not to its automodification and catalytic domain (CAT). NEDP1 KO U2OS cells were transfected with GFP, GFP-PARP-1, GFP fused to the DNA-binding domain of PARP-1 (AA 1-336) or with GFP fused to the PARP-1 automodification and catalytic domain (AA 336-1014). 24 hours post transfection, cell lysates were collected and immunoprecipitation with GFP-Trap was performed. Bound proteins were eluted and resolved by SDS-PAGE analysis, followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "GFP: 
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "NEDD8 trimers specifically bind to the second zinc finger of PARP-1. NEDP1 KO U2OS cells were transfected with GFP, GFP-PARP-1, or with GFP fused to the Zn1 domain (AA 1-96), the Zn2 domain (AA 97-215), the Zn3 domain (AA 216-336) or the Zn1+2 domains (AA 1-215) of PARP-1. 24 hours post transfection, cell lysates were collected and immunoprecipitation with GFP-Trap was performed. Bound proteins were eluted and resolved by SDS-PAGE analysis, followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "GFP: 
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "2D Gel electrophoresis of pulldowns from NEDP1 KO lysate with GST-Zn1+2 followed by Western blot analysis with α-NEDD8 antibody. Some of the 25-kDa NEDD8 band migrates to the same isoelectric point as unconjugated NEDD8 (denoted by white triangle), indicating the species is most likely an unanchored NEDD8 trimer. However, the majority of NEDD8 trimer migrates to multiple spots of lower pI (indicated in the brackets), which suggests that NEDD8 trimers undergo a post-translational modification that either adds a negative charge or blocks a positive charge on the NEDD8 trimer.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Overexpression of HDAC1 or HDAC2 decreases PARP-1-NEDD8 trimer binding. NEDP1 KO U2OS cells were transfected with GFP or GFP fused to the first two zinc finger domains of PARP-1 (GFP-Zn1+2). Cells were also co-transfected, as indicated, with empty FLAG vector, HDAC1-FLAG, or HDAC2-FLAG. 24 hours post transfection, cells were harvested and immunoprecipitation was performed on the lysates with GFP-Trap. Immunoprecipitated proteins were resolved by SDS-PAGE followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "FLAG: 
GFP: 
HDAC1: 3065
HDAC2: 3066
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "HDAC inhibition increases PARP-1-NEDD8 trimer binding. NEDP1 KO U2OS cells were transfected with GFP or GFP fused to the first two zinc finger domains of PARP-1 (GFP-Zn1+2). 24 hours later, cells were left untreated or treated with the HDAC inhibitor sodium butyrate (NaB) (10 mM) for 4 hours. Cells were harvested and immunoprecipitation was performed on the lysates with GFP-Trap. Immunoprecipitated proteins were resolved by SDS-PAGE followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "GFP: 
PARP-1: 142
NEDP1: 123228"
  },
  {
    "caption": "HDAC inhibition increases PARP-1-NEDD8 trimer binding. NEDP1 KO U2OS cells were left untreated or treated with the HDAC inhibitor sodium butyrate (NaB) (10 mM) for 4 hours. Cells were harvested and lysates were incubated with recombinant Zn1-GFP or Zn2-GFP (25 nM) for 1 hour followed by immunoprecipitation with GFP-Trap. Immunoprecipitated proteins were resolved by SDS-PAGE followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "NEDP1: 123228"
  },
  {
    "caption": "Overexpression of HDAC1 or HDAC2 in NEDP1 KO cells can rescue the induction of PAR polymer following H2O2 treatment. U2OS WT or NEDP1 KO cells were transfected with the indicated FLAG vectors. 48 post-transfection cells, were treated with H2O2 (600 μM) for the indicated amount of time and harvested directly in sample loading buffer. Lysates were resolved by SDS-PAGE and processed for Western blot analysis with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HDAC1: 3065
HDAC2: 3066
NEDP1: 123228"
  },
  {
    "caption": "(A) Differential  intron retention (IR) analysis  of RNA-seq data from samples under PABPN1  knockdown (siPABPN1) and control (NC) conditions. Significantly repressed and induced intron  retention events (retained introns, RIs) are indicated by blue and red dots, respectively. The threshold of IR  difference (ΔIR, siPABPN1-siNC) is 0.15, and the FDR cutoff is 0.01.",
    "ncbi_link": "PABPN1: 8106"
  },
  {
    "caption": "(C) Cumulative frequency distributions of retained introns  (RIs), up-regulated (red), and down-regulated (blue) upon PABPN1  knockdown, and of all retained introns  in control (NC, green) samples by their relative intronic  ranks in genes.",
    "ncbi_link": "PABPN1: 8106"
  },
  {
    "caption": "Validation of last intron retention of six representative genes in response to PABPN1  knockdown by semi-quantitative PCR in HeLa  cells treated with three different NC and PABPN1  siRNAs (D).",
    "ncbi_link": "PABPN1: 8106"
  },
  {
    "caption": "(C) RT-PCR  analysis of the spliced  and unspliced isoforms from the C3 and C4 reporters for two endogenous regulated genes LARP7  and COPS5.",
    "ncbi_link": "COPS5: 10987
LARP7: 51574"
  },
  {
    "caption": "(E) RT-PCR quantification of MS2 reporters of histone  3´end (left) and Malat1  3´end (right) for two PABPN1-regulated genes LARP7  and COPS5.",
    "ncbi_link": "COPS5: 10987
histone: 319191///319173///319172///665433///319171///319164///67334///319167///319165///319170///319166///77605///15270
LARP7: 51574
Malat1: 72289
PABPN1: 8106"
  },
  {
    "caption": "(G) Splicing  analysis of the C3, C4, and polyA  reporters in Figure 3F for endogenous genes LARP7, COPS5, and NSUN5  by RT-PCR upon PABPN1  knockdown (top) and the quantified intron retention levels (IR score) of these reporters (bottom). Data information: Data are from n=3 biologically independent experiments. The error bars represent SD. The P-values are calculated by unpaired t test (****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns, non-significant).",
    "ncbi_link": "COPS5: 10987
LARP7: 51574
NSUN5: 55695
PABPN1: 8106"
  },
  {
    "caption": "(J) Relative ratios of the unspliced isoforms (EIJ) to the spliced isoforms (EEJ) of the last introns for LARP7, DUSP12, and BRCA1  genes in HeLa  cells treated with si-PABPN1  and then rescuing PABPN1   mutants constructed in G. Data information: Data are from n=3 biologically independent experiments. The error bars represent SD. The P-values are calculated by unpaired t test (****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns, non-significant).",
    "ncbi_link": "BRCA1: 672
DUSP12: 11266
LARP7: 51574
PABPN1: 8106"
  },
  {
    "caption": "Splicing  analysis of NSUN5  and LARP7  reporter mutants by RT-PCR (E)",
    "ncbi_link": "LARP7: 51574
NSUN5: 55695"
  },
  {
    "caption": "(B) Volcano plots of the enriched proteins identified by PABPN1 TurboID-MS. Significantly enriched proteins are colored in orange, and a few representative proteins are highlighted with labels.",
    "ncbi_link": "TurboID: 
PABPN1: 8106"
  },
  {
    "caption": "(C) RT-PCR  analysis of the last intron splicing  of five representative PABPN1-dependent endogenous genes upon RBM26/27 knockdown with quantified IR values. Data information Data are from n=3 biologically independent experiments. The error bars represent SD. The P-values are calculated by unpaired t test (****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns, non-significant).",
    "ncbi_link": "PABPN1: 8106
RBM26: 64062"
  },
  {
    "caption": "(G) Cumulative frequency distributions of up-regulated RIs  upon PABPN1  (red), RBM26&27 (blue), ZC3H3  (green), and ZFC3H1  (yellow) knockdown by their relative intronic rank in genes.",
    "ncbi_link": "PABPN1: 8106
RBM26: 64062
ZC3H3: 23144
ZFC3H1: 196441"
  },
  {
    "caption": "(D) Immunofluorescence staining against Iba-1 in Cx, Hip and Cb of 3 month-old ASMko and wt mice. DAPI staining shows cell nuclei. Scale bars, 50 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(E) Mean ± SEM number of Iba-1 positive cells in different brain regions from ASMko and wt mice (n = 5 mice per group, Student´s t-test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(F) 3D rendered images obtained with Imaris Surface software from high magnification images of immunofluorescence staining against Iba-1 showing representative microglial morphology in Cx, Hip and Cb of ASMko and wt mice. Scale bars, 10 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(G) Mean ± SEM area of Iba-1 positive cells in the different brain regions from ASMko and wt mice (n = 5 mice per group, >10 cells per mouse, Student´s t-test). Scale bars, 15 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Immunofluorescence staining against Iba-1 in Cb of ASMko and wt mice treated or not with PLX for 2 months. DAPI staining shows cell nuclei. Scale bar, 100 μm. (B) Magnified images (from A) showing ramified (left) versus amoeboid (right) morphology in wt and ASMko microglia treated or not with PLX. Scale bars, 30 μm. (C) Mean ± SEM number of Iba-1 positive cells in the Cb of the different mouse groups (n = 7 mice per group, Two-way Anova, Bonferroni post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(D, E) Performance in the Rotarod test of ASMko and wt mice treated or not with PLX for 2 months expressed as the mean ± SEM time spent in the rotating rod on each of four trials (D) or the mean ± SEM time of the four trials (E) (n = 7 mice per group, Two-way Anova, Games-Howell (D) and Bonferroni (E) post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(F) Mean ± SEM body weight of ASMko and wt mice treated or not with PLX at the indicated time during long-term treatment (n= 7 mice per group, Two-way Anova, Bonferroni post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(G) Survival curve of ASMko and wt mice with or without long-term PLX treatment (n = 7 mice per group).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(H) Immunofluorescence staining against the PC marker Calbindin in mid and posterior lobules of Cb in ASMko and wt mice treated or not with PLX for 2 months. DAPI staining shows cell nuclei. Scale bar, 500 μm. (I) Mean ± SEM number of Calbindin positive cells in the anterior (lobules I-V), middle (lobules VI-VIII) and posterior zone (lobules IX-X) of the Cb from the different mouse groups (n = 7 mouse per group, Two-way Anova, Bonferroni post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Immunofluorescence staining against CD16/CD32 or Arg-1 in Cb of ASMko mice (red). Microglia were identified by F4/80 or Iba-1 staining (green). DAPI staining shows cell nuclei. Scale bar, 50 μm. (B) Mean ± SEM number of Arg-1 and CD16/CD32 positive microglia per area in Cb from ASMko and wt mice (n = 6 mice per group). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(C) Mean ± SEM levels of TNFa protein in the Cb from ASMko and wt mice measured by ELISA (n = 7 mice per group, Student´s t-test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(D) Mean ± SEM levels of TNFa mRNA in Cb of ASMko and wt mice determined by qRT-PCR (n = 7 mice per group, Student´s t-test).",
    "ncbi_link": "ASM: 20597
TNFa: 21926"
  },
  {
    "caption": "(E) Survival after LPS challenge in ASMko and wt mice treated or not with dexamethasone (n = 8 mice per group).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(F) Immunofluorescence staining against MBP in Cb of ASMko and wt mice treated or not with PLX for 2 months. Scale bar, 50 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(H) High magnification of immunofluorescence staining against MBP in ASMko mice treated or not with PLX for 2 months. White arrows show MBP aggregates indicative of myelin debris. Scale bar, 50 μm. (I) Mean ± SEM number of MBP aggregates per cell area in the different mouse groups (n = 7 mice per group, Student´s t-test). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(J) High magnification images and their 3D rendered replicates from cerebellar wt and ASMko microglia identified by Iba-1 and of the myelin marker MBP. Scale bars, 10 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(K) Amplified image and its 3D rendered replicate of amoeboid microglia containing myelin debris (arrowheads) in the ASMko cerebellum. The orthogonal projection of this cell in the lower panels confirms the presence of the myelin debris inside the cell and underneath the plasma membrane (arrowhead). DAPI staining shows cell nuclei. Scale bars, 10 μm. (L) Mean ± SEM percentage of microglia showing internalised myelin debris in wt and ASMko mice (n = 7 mice per group). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Transmission electron microscopy image of microglia in the Cb of ASMko mice showing accumulation of multillamelar vacuoles and other lysosome related vesicles filling the whole cytoplasm of these cells. Arrowhead identifies the nuclei. Scale bar, 5 μm. On the right, higher magnification showing a multillamelar body (arrowhead) with the characteristic concentric lamellar inclusions. Scale bar, 0.5 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(E) Lysotracker-Red staining in BMDMs from wt and ASMko mice. Scale bar, 10 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(F) Western blot of CathB levels and the cytosolic protein GAPDH in the cellular and cytosolic fractions of wt and ASMko BMDMs extracted with digitonin (left). Mean ± SEM pro-CathB and CathB levels in the cytosolic fractions (right) (n=2 cultures per genotype, Student´s t-test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(G) Immunofluorescence staining against Iba-1 (green) and CathB (red) in Cb of ASMko and wt mice. Arrowheads show double positive cells. Scale bar, 50 μm. Below, magnified images of the selected areas. Scale bar, 20 μm. (H) Immunofluorescence staining against CathB (green), Arg-1 (red, anti-inflammatory microglia) and F4/80 (yellow, all microglia) in Cb of ASMko mice. DAPI staining shows cell nuclei. Scale bar, 50 μm. Below, magnified images of the selected areas. Scale bar, 20 μm. (I) Table showing mean ± SEM percentage of microglia presenting CathB staining (CathB +/Iba-1+), and the number of CathB positive microglia co-expressing Arg-1 (CathB+/Arg-1+) in Cb of ASMko and wt mice (n = 5 mice, >10 cells per mouse). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Western blot of CathB levels (for both the precursor (pro-CathB) and the cleaved-mature forms) in the culture media from ASMko and wt BMDMs. Staining of Ponceau-S is shown as loading control. (B) Mean ± SEM fold increase in CathB levels in the culture media from wt and ASMko BMDMs (n = 5 independent cultures, Student´s t-test). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(C) Immunofluorescence staining against LAMP-1 (yellow) and Iba-1 (red) in Cb of ASMko and wt mice. Scale bar, 50 μm, zoomed images 20 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(D) Immunofluorescence staining against LAMP-1 in non-permeabilised BMDMs from ASMko and wt mice. Scale bar, 50 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(E) Mean ± SEM of LAMP-1 levels on the surface of ASMko and wt BMDMs (n = 4 independent cultures, >40 cells per culture, Student´s t-test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(F) Mean ± SEM microvesicle and exosome numbers in the culture media from ASMko and wt BMDMs (n = 6 independent cultures, Student´s t-test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(G) Western blot of CathB and Flotillin1 levels in the secreted exosome fractions from ASMko and wt BMDMs. (H) Western blot of CathB levels in the exosome depleted culture media from wt and ASMko BMDMs.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(I) Mean ± SEM MTT absorbance reflecting cell viability in primary neurons from wt mice treated with conditioned media from ASMko and wt BMDMs in the presence or absence of the CathB inhibitor Ca074 (n = 4 independent cultures Two-way Anova, Bonferroni post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(K) Mean ± SEM percentage of CathB positive microglia in resistant and sensitive Cb lobules of ASMko mice (n = 5 mice, χ2 test).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(L) Western blot of Cath B and β-Actin levels in cerebellar extracts of wt and ASMko mice treated or not with PLX. (M) Mean ± SEM of CathB levels normalized by β-Actin in cerebellar extracts of wt and ASMko mice treated or not with PLX (n= 6 mice Two-way Anova, Bonferroni post hoc). ",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(O) Western blot of CathB levels (for both the precursor (pro-CathB) and the cleaved-mature forms) in the culture media from ASMko and wt cerebellar organotypic cultures from mice fed with vehicle (veh) or PLX (PLX). Below, Western blots of organotypic culture lysates against Iba-1, to confirm microglia depletion, and against GAPDH as loading control.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(P) Mean ± SEM increase in pro-CathB (left) and CathB (right) levels in the culture media from cerebellar organotypic cultures from wt and ASMko mice treated or not with PLX (n = 3 mice per group Two-way Anova, Bonferroni post hoc).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Mean ± SEM body weight of ASMko and wt mice treated or not with Ca074Me at the indicated time during treatment (n = 7 mice per group).",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "Performance in the Rotarod test of ASMko and wt mice treated or not with Ca074Me for 1 month expressed as mean ± SEM time spent in the rotating rod on each of four trials (B)",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "Performance in the Rotarod test of ASMko and wt mice treated or not with Ca074Me for 1 month expressed as mean ± SEM time of the four trials (C)",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(D) Immunofluorescence staining against the PC marker Calbindin in the posterior lobules of the Cb in ASMko and wt mice treated or not with Ca074Me for 1 month. DAPI staining shows cell nuclei. Scale bar, 200 μm.",
    "ncbi_link": "ASM: 20597"
  },
  {
    "caption": "(A) Immunofluorescence staining against Iba-1 in Cx, Hip and Cb of 2 month-old Npc1nmf164 and wt mice. DAPI staining shows cell nuclei. Scale bars, 30 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(B) 3D rendered images obtained with Imaris Surface software from high magnification z-stack images of immunofluorescence staining against Iba-1 showing representative microglial morphology in Cx, Hip and Cb of Npc1nmf164 and wt mice. Scale bars, 10 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(C) Mean ± SEM number (upper panel) and area (lower panel) of Iba-1 positive cells in different brain regions from Npc1nmf164 and wt mice (n = 5 mice per group, >30 cells per mouse, Student´s t-test).",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(E) Immunofluorescence staining against MBP in Cb of Npc1nmf164 and wt mice. Scale bar, 50 μm. Graph shows mean ± SEM number of MBP aggregates per area (n = 5 mice per group, Student´s t-test).",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(F) High magnification images and their 3D rendered replicates from cerebellar Npc1nmf164 microglia stained against Iba-1 and MBP containing myelin debris (arrowheads). Scale bars, 10 μm (up), 2 μm (down). The orthogonal projection of the cells in the right panels confirms the presence of myelin debris inside the cell and underneath the plasma membrane. DAPI staining shows cell nuclei. Scale bars, 10 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(G) Mean ± SEM percentage of microglia showing internalised myelin debris in wt and Npc1nmf164 mice (n = 5 mice per group).",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "(H) Immunofluorescence staining against F4/80 and CathB in Cb of Npc1nmf164 mice. Scale bar, 30 μm. The table shows mean ± SEM percentage of microglia presenting CathB staining in Npc1nmf164 and wt mice. Below, magnified images of the selected areas. Scale bar, 20 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "D qRT-PCR expression analyses of PIN1-4 from whole root and roo tip samples, respectively, Col-0 RNA was extracted with respective organs and first-strand cDNA was then synthesized (n = 3).",
    "ncbi_link": "PIN1: 843693"
  },
  {
    "caption": "B: Hippocampal neurons transduced with GFP-TDP-25 constructs (DIV5+8) or GFP-TDP-43 (DIV5+4 due to higher toxicity) were sequentially extracted with RIPA buffer followed by 2% SDS buffer and analyzed via immuoblotting. Left panel shows representative immunoblot for GFP and loading control Calnexin. Right panel shows quantification of the ratio of the respective GFP densiometric signal in SDS extract to RIPA extract. Barplots showing mean ± SD from n=3 independent experiments. TDP-43 (0.039 ± 0.029, mean ± CI) vs TDP-25 wt (1.22 ± 0.296) vs TDP-25 mut (0.928 ± 0.564): F(2,6)=51.4, ***p=0.000168, η²=0.94. TDP-43 vs TDP-25 wt: ***p=1.67*10-4, TDP-43 vs TDP-25 mut: p=7.983*10-4, TDP-25 wt vs TDP-25 mut: p=0.1182,",
    "ncbi_link": "TDP-25: 23435"
  },
  {
    "caption": "(A-D) Primary rat hippocampal neurons were transduced with GFP-TDP-25 variants, GFP-NPM1 or Htt97Q-GFP and analyzed by fluorescence recovery after photobleaching (FRAP) at DIV5+8, except Htt97Q-GFP which was analyzed at DIV5+6 to avoid excessive toxicity. Example images with indicated bleach regions (dashed circles) are shown (A, C). Scale bar = 1.5 µm. Resulting normalized FRAP curves (relative fluorescence intensity over time) with values representing means ± SD are shown in (B, D). (B) Comparison of the averaged recovery fraction of the last six timepoints obtained from three independent experiments. GFP-NPM1 (0.982 ± 0.019, mean ± CI, n=37 cells) vs GFP-TDP-25 wt (0.097 ± 0.013, n=35 cells) vs GFP-TDP-25 mut (0.085 ± 0.006, n=38 cells): H(1)=74.134, df=2, ***p<2.2*10-16, η²[H]=0.674, Kruskal-Wallis Test. GFP-NPM1 vs GFP-TDP-25 wt: ***p<2*10-16, GFP-NPM1 vs GFP-TDP-25 mut: p<2*10-16, GFP-TDP-25 wt vs GFP-TDP-25 mut: p=0.11, Pairwise Wilcoxon Rank Sum Tests with Benjamini-Hochberg correction. In (D), the recovery fraction averaged at >20 min timepoints was compared from four independent experiments. Htt97Q-GFP (0.094 ± 0.017, n=25 cells) vs GFP-TDP-25 wt (0.312 ± 0.041, n=23 cells) vs GFP-TDP-25 mut (0.271 ± 0.029, n=24 cells): H(1)=46.376, df=2, ***p=8.501*10-11, η²[H]=0.643, Kruskal-Wallis Test. Htt97Q-GFP vs GFP-TDP-25 wt ***p=1.9*10-11, Htt97Q-GFP vs GFP-TDP-25 mut ***p=4.3*10-12, GFP-TDP-25 wt vs GFP-TDP-25 mut: p=0.12, Pairwise Wilcoxon Rank Sum Tests with Benjamini-Hochberg correction.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "E: Immunofluorescence of hippocampal neurons transduced with GFP, GFP-TDP-25 wild-type or mutant and treated with MG132 (10 µM, 14h, DIV5+8). Representative images of GFP-TDP-25 inclusions and diffuse cytoplasmic staining. Automated quantification of GFP intensity normalized to the number of DAPI stained nuclei (omitted here for clarity) in MG132 treated cells compared to DMSO control. Counterstain to label the neuronal cytoskeleton (MAP2). Scale bar = 10 µm. Box plot as in Fig. 3C. GFP (1.23 ± 0.393, n=5 independent experiments) vs GFP-TDP-25 wt (2.11 ± 0.804, n=5) vs GFP-TDP-25 mut (2.36 ± 1.16, n=5): H(1)=7.34, df=2, p=0.02548, η²[H]=0.445, Kruskal-Wallis test. GFP vs GFP-TDP-25 wt: *p=0.048, GFP vs GFP-TDP-25 mut: *p=0.048, GFP-TDP-25 wt vs GFP-TDP-25 mut: p=0.690, Pairwise Wilcoxon Rank Sum Tests with Benjamini-Hochberg correction.",
    "ncbi_link": "GFP: 
TDP-25: 23435"
  },
  {
    "caption": "Representative false colour images of leaf surface temperature captured by a thermal camera from WT, stp1-1, stp4-1, stp1stp4, stp13, stp1stp13 and stp4stp13 plants.",
    "ncbi_link": "stp13: 832703
stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Whole-plant recordings of changes in stomatal conductance (gs) from WT, stp1-1, stp4-1 and stp1stp4 plants. Data shown are means ± SEM; n ≥ 3 per genotype.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Whole-plant recordings of changes in stomatal conductance (gs) from self-grafted donor lines (WT/WT, stp1stp4/stp1stp4) and reciprocal grafting of shoot/root (WT/stp1stp4, stp1stp4/WT) plants. Data shown are means ± SEM; n = 3 per genotype.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Content of soluble sugars in guard cell-enriched epidermal peels of WT and stp1stp4 plants at the end of the night (EoN) and after 40 min of illumination with white light at 150 µmol m-2 s-1 following the EoN. Data for two independent experiments are shown; means ± SEM; n ≥ 7 per genotype and time point.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Representative confocal laser microscopy images of propidium iodide-stained guard cell starch granules of intact leaves of WT, stp1-1, stp4-1, stp1stp4, suc1 and suc3 plants. Scale bar, 10 µm.",
    "ncbi_link": "stp1: 837667
stp4: 821531
suc1: 843519
suc3: 814817"
  },
  {
    "caption": "Starch dynamics in guard cells of intact leaves of WT, stp1-1, stp4-1, stp1stp4, suc1 and suc3 plants at the end of the night (EoN) and after one and three hours of illumination with 150 µmol m-2 s-1 of white light. Data for three independent experiments are shown; means ± SEM; n = 120 individual guard cells per genotype and time point.",
    "ncbi_link": "stp1: 837667
stp4: 821531
suc1: 843519
suc3: 814817"
  },
  {
    "caption": "Representative false colour images of photosystem II (PSII) operating efficiency (ΦPSII) captured by chlorophyll fluorescence imaging from WT, stp1-1, stp4-1 and stp1stp4 plants. ΦPSII was measured at a photosynthetically active radiation (PAR) of 440 µmol m-2 s-1.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Whole-plant recordings of changes in CO2 assimilation (A) from WT, stp1-1, stp4-1 and stp1stp4 plants. Data shown are means ± SEM; n ≥ 3 per genotype.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Whole-plant recordings of changes in CO2 assimilation (A) from self-grafted donor lines (WT/WT, stp1stp4/stp1stp4) and reciprocal grafting of shoot/root (WT/stp1stp4, stp1stp4/WT) plants. Data shown are means ± SEM; n = 3 per genotype.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Representative Red Green Blue (RGB) images of 3-(day 0) and 4-week-old (day 7) WT, stp1-1, stp4-1 and stp1stp4 plants.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Photosynthetic CO2 assimilation (A) in dark-adapted WT and stp1stp4 plants in response to a step increase in CO2 concentrations from 0 to 1000 ppm. Data shown are means ± SEM; n=3 per genotype.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Representative Red Green Blue (RGB) images of 3-(day 0) and 4-week-old (day 6) WT and stp1stp4 plants grown under 600 ppm CO2.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Representative confocal laser microscopy images of propidium iodide-stained guard cell starch granules of intact leaves of WT and stp1stp4 plants grown under 600 ppm CO2. Scale bar, 10 µm.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "Starch dynamics in guard cells of intact leaves of WT and stp1stp4 plants grown under 600 ppm CO2 at the end of the night (EoN) and after one and three hours of illumination with 150 µmol m-2 s-1 of white light. Data for two independent experiments are shown; means ± SEM; n = 80 individual guard cells per genotype and time point.",
    "ncbi_link": "stp1: 837667
stp4: 821531"
  },
  {
    "caption": "(A, B) Fluorescence confocal microscopy images show TMRE staining and GFP::MIRO-1 in WT and fzo-1 mutants animals. Dashed lines outline regions where fluorescence intensity was quantified.",
    "ncbi_link": "fzo-1: 173990"
  },
  {
    "caption": "(C) Immunoblot shows protein levels of MIRO-1 in WT and fzo-1 mutant animals, with tubulin and COX-4 serving as loading controls.",
    "ncbi_link": "fzo-1: 173990"
  },
  {
    "caption": "(D) Fluorescence confocal images show GFP::MIRO-1 and mito::mKate2 in WT and fzo-1 mutants. (E) Quantification of MIRO-1::GFP levels in WT and fzo-1 mutants. n≥33, biological replicates.",
    "ncbi_link": "fzo-1: 173990"
  },
  {
    "caption": "(A) Representative confocal images show the TMRE and mito::GFP signals in WT, miro-1(tm1966), miro-1(ΔEF) (EF-hand domain mutation), and miro-1(OE, overexpression) animals. (B) Quantitation of TMRE and mito::GFP signal (normalized ratio of TMRE fluorescence to mito::GFP fluorescence). n > 200 mitochondria.",
    "ncbi_link": "miro-1: 177238"
  },
  {
    "caption": "(D) ATP content of crude isolated mitochondria from WT and miro-1(tm1966) mutants as measured with a commercial luminescence kit. n = 3, biological replicates.",
    "ncbi_link": "miro-1: 177238"
  },
  {
    "caption": "(D) Western blot analysis of the interaction between MIRO-1 and VDAC-1 by coimmunoprecipitating with GFP nanobody-conjugated beads in GFP::MIRO-1 animals and detected by GFP and VDAC-1 antibodies.",
    "ncbi_link": "GFP: 
MIRO-1: 177238"
  },
  {
    "caption": "(E) Western blot analysis of the interaction between MIRO-1 and VDAC-1 by coimmunoprecipitating with VDAC-1 antibody-conjugated beads in GFP::MIRO-1 animals and detected by GFP and VDAC-1 antibodies.",
    "ncbi_link": "GFP: 
MIRO-1: 177238"
  },
  {
    "caption": "(H) BN-PAGE and immunoblot analysis of the total worm lysate of GFP::MIRO-1 (KI) by GFP and VDAC-1 antibodies. Green shading highlights the complex that contained MIRO-1 and VDAC-1 proteins.",
    "ncbi_link": "GFP: 
MIRO-1: 177238"
  },
  {
    "caption": "(A) Schematic of the vdac-1 transgene by CRISPR-Cas9 method. The images below show the young adult stage worms of WT and vdac-1(zju247) mutants. (B) Representative confocal images showing TMRE staining and mito::GFP in L4440, vdac-1 RNAi, vdac-1(zju247), and vdac-1 OE animals.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
vdac-1: 177524"
  },
  {
    "caption": "(E) ATP content in crude isolated mitochondria of WT animals and vdac-1(zju247) mutants. Quantification is conducted with a commercial luminescence kit. n = 3, biological replicates.",
    "ncbi_link": "vdac-1: 177524"
  },
  {
    "caption": "(B) Immunoprecipitation of GFP::MIRO-1 and GFP::MIRO-1(E473G) with GFP nanobody-conjugated beads.",
    "ncbi_link": "GFP: 
MIRO-1: 177238"
  },
  {
    "caption": "(F) Immunoprecipitation of GFP::MIRO-1 in fzo-1 mutant with GFP nanobody-conjugated beads. The interaction between GFP::MIRO-1 and VDAC-1 is increased in fzo-1 mutants.",
    "ncbi_link": "fzo-1: 173990"
  },
  {
    "caption": "(G) BN-PAGE and immunoblot analysis of VDAC-1 oligomerization crosslinked with BMH in WT and miro-1(tm1966) mutants using VDAC-1 antibody.",
    "ncbi_link": "miro-1: 177238"
  },
  {
    "caption": "A HT-29  cells were transfected with NC, siRIPK1 or  miR-324-5p. After 48 h, cells were treated with  TNF-α (T) or T+S+Z for an additional 6 h.  Western blotting  analysis of p-RIPK1, RIPK1, p-RIPK3, RIPK3, p-MLKL, MLKL  and β-actin.",
    "ncbi_link": "miR-324-5p: 442898
RIPK1: 8737"
  },
  {
    "caption": "B  Western blotting  analysis of RIPK1, RIPK3, MLKL  and β-actin levels in  HT-29  cells that were transfected with NC, siRIPK1, siRIPK3, MLKL  siRNA oliogs ( siMLKL), and miR-324-5p.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259
RIPK1: 8737
RIPK3: 11035"
  },
  {
    "caption": "C HT-29 cells were harvested 48 h after transfection with NC, siMLKL, and miR-324-5p. MLKL   expression was analyzed by qPCR  (upper) or RT-PCR (lower). Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "D, E MKN45  (D) and 174T  (E) cells were harvested 48 h after transfection with NC, siMLKL, and miR-324-5p. qPCR  analysis for the expression of MLKL  (upper) and western blotting  analysis of MLKL  and β-actin (lower). Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "F  HT-29 cells were transfected with NC, siMLKL,  miR-324-5p, or anti-miR-324-5p. After 48 h, cells were treated with DMSO  or T+S+Z for an additional 24 h. Cell survival  was determined by measuring ATP  levels. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "G Western blotting  analysis of MLKL and β-actin in HT-29 cells that were harvested 48 h after transfection with NC, siMLKL, miR-324-5p, or an anti-miR-324-5p.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "B HEK293T cells were transfected with NC, MLKL  siRNA oligos targeting the 3'UTR of MLKL  (siMLKL-3'UTR), or miR-324-5p, together with pmirGLO-MLKL-3'UTR or the mutated form of MLKL-3'UTR shown in A. Relative luciferase activity  analysis of MLKL-3'UTR. Data are presented as firefly luciferase activity/renilla luciferase activity ± SD. In B, data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "C HEK293T  cells were transfected with NC, miR-324-5p, or the mutated form of miR-324-5p  together with pmirGLO-MLKL-3'UTR. Relative  luciferase activity analysis of MLKL-3'UTR. Data are presented as firefly luciferase activity/renilla luciferase activity ± SD (n=5, biological replicates).",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "D Western blotting  analysis of MLKL  and  β-actin  in HeLa-endogenous MLKL  cells (HeLa  cells stably expressing human RIPK3) and HeLa-exogenous MLKL  cells (Mlkl-/- HeLa  cells stably expressing human RIPK3  and the coding sequence (CDS) of MLKL) that were harvested 48 h after transfection with NC, miR-324-5p, or MLKL  siRNA oligos targeting the CDS region of MLKL  (siMLKL-CDS).",
    "ncbi_link": "miR-324-5p: 442898
Mlkl: 197259
MLKL: 197259
RIPK3: 11035"
  },
  {
    "caption": "E qPCR  analysis for the expression of MLKL  in HeLa-exogenous MLKL  cells that were harvested 48 h after transfection with NC, miR-324-5p, siMLKL-3'UTR, or siMLKL-CDS. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "F, G HeLa-endogenous MLKL  cells (F) and HeLa-exogenous MLKL  (G) were transfected with NC, miR-324-5p, siMLKL-3'UTR, or siMLKL-CDS. After 48 h, cells were treated with T+S+Z for 24 h. Cell survival  was determined by measuring ATP  levels. Data information: The number of surviving  cells was normalized to the number of surviving  control cells, which were treated with DMSO. data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "H HeLa  cells expressing MLKL(1-190 aa) fused to DmrB  (HeLa-MLKL(1-190)-Dmir  cells) were transfected with NC, miR-324-5p, siMLKL-3'UTR, or siMLKL-CDS. After 48 h, cells were treated with DMSO  or the dimerization agent AP20187  (60 nM) for 24 h. Cell survival   was determined by measuring ATP  levels. Data information: The number of surviving  cells was normalized to the number of surviving  control cells, which were treated with DMSO. data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "C  African green monkey kidney epithelial  (Vero) cells were transfected with NC, siMLKL, or miR-324-5p for 48 h. qPCR  analysis for the expression of MLKL. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 119618165"
  },
  {
    "caption": "D MEFs  were transfected with NC, siMLKL, or miR-324-5p  for 48 h. qPCR analysis for the expression of MLKL and western blotting  analysis of MLKL and β-actin. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown. β-actin serves as an internal control (D).",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 74568"
  },
  {
    "caption": "E MEFs  were transfected with NC, siMLKL, or miR-324-5p. After 48 h, cells were treated with DMSO  or T+S+Z for 24 h. Cell viability was determined by measuring ATP  levels. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 74568"
  },
  {
    "caption": "F HEK293T  cells were transfected with NC or miR-324-5p, together with pmirGLO-mouse MLKL-3'UTR or the mutated form of mouse MLKL-3'UTR. Relative  luciferase activity analysis of MLKL-3'UTR. Data are presented as firefly luciferase activity/renilla luciferase activity ± SD (n = 5, biological replicates).",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 74568"
  },
  {
    "caption": "A U937  cells were treated with 100 ng/ml IFN-α, 100 ng/ml  IFN-β, 100 ng/ml  IFN-γ, 100 ng/ml LPS, or 25 μg/ml poly(I:C) for 24 h. Identical concentrations were used in later experiments unless otherwise stated. qPCR  analysis for the expression of MLKL. C U937  cells were treated with PBS, IFN-α, IFN-β, IFN-γ, LPS, or poly(I:C)  for 24 h. qPCR  analysis for the expression of miR-324-5p. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "D, E U937 cells were transfected with NC, siMLKL, or miR-324-5p. After 48 h, cells were treated with IFN-β (D) or IFN-γ (E) for 24 h. Western blotting analysis of MLKL  and β-actin.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "F, G U937  cells were incubated with 300 nM ruxolitinib  for 2 h prior to  IFN-β (F) or   IFN-γ (G) treatment. After 24 h, qPCR  analysis for the expression of miR-324-5p. After 48 h, western blotting  analysis of p-STAT1, STAT1, MLKL  and β-actin. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898"
  },
  {
    "caption": "H, I U937  cells were transfected with NC, or STAT1  siRNA oliogs (siSTAT1). After 48 h, cells were treated with IFN-β (Η) or  IFN-γ (Ι). qPCR  analysis for the expression of miR-324-5p. Western blotting analysis of STAT1, MLKL  and β-actin. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
STAT1: 6772"
  },
  {
    "caption": "J HT-29 cells were treated with   IFN-γ for 24 h. The cell lysate was collected for ChIP  analysis. STAT1 binding  to miR-324-5p  promoter DNA region was determined by Chip-qPCR. The amount of precipitated DNA was calculated as percent input. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898"
  },
  {
    "caption": "A U937  cells were transfected with NC, siMLKL-3'UTR, or  miR-324-5p. After 48 h, cells were exposed to 100 ng/ml IFN-γ plus 20 μM  z-VAD for 24 h. Identical concentrations were used in later experiments unless otherwise stated. Cell viability was determined by measuring ATP  levels. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "B qPCR  analysis for the expression of MLKL  (left) and miR-324-5p (middle) in PBMC-derived macrophages  that were treated with PBS  or IFN-γ for 24 h. The corresponding  western blotting analysis of MLKL  and β-actin (right). Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "C, D PBMC-derived macrophages  (C) and HT-29 cells (D) were transfected with NC, siMLKL, or miR-324-5p. After 48 h, cells were exposed to S+Z or  IFN-γ+S+Z for 24 h. Cell viability  was determined by measuring ATP  levels (left). The corresponding western blotting analysis of MLKL  and β-actin (right). Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "E qPCR  analysis for the expression of miR-324-5p in miR-324-5p knockout HT-29  cells (miR-324-5p-/- cells) . Altered miR-324-5p DNA sequences were shown in  miR-324-5p-/- clone 19# and 36#. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898"
  },
  {
    "caption": "F MiR-324-5p+/+ HT-29, miR-324-5p-/- -19# , and miR-324-5p-/- -36# cells were treated with T+S+Z for the indicated times. Cell viability  was determined by measuring ATP  levels. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "MiR-324-5p: 442898
miR-324-5p: 442898"
  },
  {
    "caption": "G, H MiR-324-5p+/+ HT-29, and miR-324-5p-/- HT-29 cells were treated with IFN-β  (G) or IFN-γ (H) plus 20 μM z-VAD for 24 h. Cell viability was determined by measuring ATP  levels. Data information: Data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "MiR-324-5p: 442898
miR-324-5p: 442898"
  },
  {
    "caption": "A qPCR  analysis for the expression of IFN-β  (left) and IFN-γ (right) in PBMC-derived macrophages  that were infected with IAV  (H1N1 strain PR8) at an multiplicity of infection (MOI) of 0.2 for 24 h. B qPCR  analysis for the expression of MLKL  (left) and miR-324-5p (right) in PBMC-derived macrophages  that were treated with the 300nM ruxolitinib  for 2 h prior to the infection with IAV  (MOI=0.2) for 24 h. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "IFN-β: 3456
IFN-γ: 3458
miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "C PBMC-derived macrophages  were transfected with NC, siMLKL, or miR-324-5p. After 48h, cells were treated with S+Z in the presence or absence of IAV  (MOI=0.2) for 24 h. Cell viability was determined by measuring ATP  levels. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "D qPCR  analysis for the expression of M gene of IAV  in PBMC-derived macrophages  that were transfected with NC, siMLKL or miR-324-5p  for 48h, followed by the infection with IAV  (MOI=0.2) for 24 h. Data information: data are represented as the means ± SD of three biological replicates. Statistical analyses were performed using unpaired Student's t-test. All experiments were performed at least three times, and representative data are shown.",
    "ncbi_link": "M gene: 23308107
miR-324-5p: 442898
MLKL: 197259"
  },
  {
    "caption": "C. Ki67, α-MHC, and DAPI staining and quantification of CMs treated with control (Ctrl), or combinations of a FoxM1 up-regulation adenovirus (F), Id1 up-regulation adenovirus (I), Hmgb2 up-regulation adenovirus (H) or a small molecule Jnk3 inhibitor (Ji).",
    "ncbi_link": "FoxM1: 14235
Hmgb2: 97165
Id1: 15901"
  },
  {
    "caption": "D. Ki67, α-MHC, and DAPI staining and quantification of CMs treated with Ctrl or combination of FI with Jnk3-shRNAs in place of the small molecule (Ji). The arrow head indicates Ki67+/α-MHC+ proliferated CMs.",
    "ncbi_link": "Jnk3: 26414"
  },
  {
    "caption": "G. RNA expression ratio of Oct4, FoxM1, Id1, or Jnk3 in doxycycline-injected versus control adult CMs isolated from reprogrammable mice.",
    "ncbi_link": "FoxM1: 14235
Id1: 15901
Jnk3: 26414
Oct4: 18999"
  },
  {
    "caption": "B. RNA expressional changes of FoxM1, Id1, and Jnk3 after adeno-Ctrl or adeno-FIJs treatment after MI.",
    "ncbi_link": "FoxM1: 14235
Id1: 15901
Jnk3: 26414"
  },
  {
    "caption": "A. RNA expression of mitosis checkpoint genes in CMs with FoxM1 or Id1 overexpression, Jnk3-shRNA, or combined treatment.",
    "ncbi_link": "FoxM1: 14235
Id1: 15901
Jnk3: 26414"
  },
  {
    "caption": "B. Transcriptional expression of cyclin-dependent kinases in FoxM1 or Id1 up-regulated, Jnk3 down-regulated, or combined treated CMs.",
    "ncbi_link": "FoxM1: 14235
Id1: 15901
Jnk3: 26414"
  },
  {
    "caption": "C. Real-time RT-PCR analysis of CDK inhibitor expression in CMs with FoxM1 or Id1 overexpression, Jnk3-shRNA or combined treatment.",
    "ncbi_link": "FoxM1: 14235
Id1: 15901
Jnk3: 26414"
  },
  {
    "caption": " A Immunofluorescence of unpermeabilized stably transfected MDCK cells shows that, unlike wt full-length UMOD, mutants ZP-N (R415A) or ZP-C (ΔFA) do not assemble into filaments. Scale bar: 50 µm. ",
    "ncbi_link": "UMOD: 7369"
  },
  {
    "caption": " B-G Immunofluorescence of unpermeabilized cells co-expressing FLAG-tagged wt UMOD (green) and the indicated HA-tagged isoforms (red). UMOD R415A does not incorporate into polymers that only contain wt protein (C). UMOD ΔFA has a dominant negative effect on wt protein polymerization (D) that is rescued in a double mutant carrying both ZP-N and ZP-C mutations (F). Similarly, the dominant negative effect of a CCS mutation (4A) that prevents EHP dissociation (E) is suppressed by the introducing the R415A mutation in the 4A isoform (G). Scale bar: 50 µm. ",
    "ncbi_link": "FLAG: 
HA: 
UMOD: 7369"
  },
  {
    "caption": " H Immunofluorescence of permeabilized cells expressing soluble isoforms of UMOD truncated before the EHP (UMOD-CCS) shows that wt forms intracellular polymers whereas polymerization interface mutants do not. The intracellular polymers are localized in the endoplasmic reticulum (ER), as shown by co-staining with the KDEL sequence used as ER marker. Scale bar: 10 µm. ",
    "ncbi_link": "UMOD: 7369"
  },
  {
    "caption": "(A) Left: qRT-PCR analysis of mRNA expression of MAPK12 (p38gamma) and MAPK13 (p38delta) in liver extracts prepared from obese patients with alcoholic fatty liver disease (NAFLD) and control individuals without NAFLD. mRNA expression was normalized to the amount of Gapdh mRNA. Right: Representative H&E-stained liver sections. Scale Bar: 50μm. (n= 11-74)",
    "ncbi_link": "Gapdh: 
MAPK12: 6300
MAPK13: 5603"
  },
  {
    "caption": "(B) Left: qRT-PCR analysis of mRNA expression of MAPK12 (p38gamma) and MAPK13 (p38delta) in liver extracts prepared from control patients with NAFLD/non-alcoholic steatohepatitis (NASH) and control individuals without NAFLD/NASH. mRNA expression was normalized to the amount of Gapdh mRNA. Right: Representative H&E-stained liver sections. Scale Bar: 50μm. (n= 11-9)",
    "ncbi_link": "Gapdh: 
MAPK12: 6300
MAPK13: 5603"
  },
  {
    "caption": "(D) qRT-PCR analysis of Mapk12 (p38gamma) and Mapk13 (p38delta) mRNA expression in liver extracts prepared from wild-type mice (WT) fed a diet deficient in methionine and choline (MCD) or control diet (ND) for 3 weeks; mRNA expression was normalized to the amount of Gapdh mRNA. (n=5-10)",
    "ncbi_link": "Gapdh: 
Mapk12: 29857
Mapk13: 26415"
  },
  {
    "caption": "(A) Representative H&E and oil red-stained liver sections prepared from WT and p38γ/δ-/- mice fed a ND or the MCD diet for 3 weeks. Scale Bar: 50μm.",
    "ncbi_link": "p38γ: 29857"
  },
  {
    "caption": "(B) Liver triglycerides and (C) plasma transaminase activity (ALT) measured in WT and p38γ/δ-/- mice after 3 weeks of MCD diet.",
    "ncbi_link": "p38γ: 29857"
  },
  {
    "caption": "(E) qRT-PCR analysis of Col1a1, Acta2 and Timp1 mRNA expression. mRNA expression was normalized to the amount of Gapdh mRNA.",
    "ncbi_link": "Gapdh: 
Acta2: 11475
Col1a1: 12842
Timp1: 21857"
  },
  {
    "caption": "(F) Representative Masson's trichrome-stained liver sections prepared from WT and p38γ/δ-/- mice fed a ND or the MCD diet for 3 weeks. Scale Bar: 50μm. Data are means ± SEM (n=5-10). *P<0.05; **P<0.01; ***P<0.001 (2-way ANOVA coupled to Bonferroni's post tests).",
    "ncbi_link": "p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a MCD diet for 3 weeks. (A) Representative H&E and oil red stained liver sections. Scale Bar: 50μm. (n=5-10).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a MCD diet for 3 weeks. (B) Liver triglycerides (C) and plasma ALT at the end of the diet period.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a MCD diet for 3 weeks. (D) Measurement of plasmaTNF-α and IL-6.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a MCD diet for 3 weeks. (E) qRT-PCR analysis of myeloid cell markers and cytokine mRNA expression from liver tissue; mRNA expression was normalized to the amount of Gapdh mRNA.",
    "ncbi_link": "Cre: 
Gapdh: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a MCD diet for 3 weeks. (F) qRT-PCR analysis of M1 and M2 polarization cell markers from liver infiltrated macrophages. mRNA expression was normalized to the amount of Gapdh mRNA. Data are means ± SEM (n=5-10). *P<0.05; **P<0.01; ***P<0.001 (2-way ANOVA coupled to Bonferroni's post tests).",
    "ncbi_link": "Cre: 
Gapdh: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a high-fat diet (HFD) for 10 weeks. (A) Body weight measured at the indicated times during HFD treatment.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a high-fat diet (HFD) for 10 weeks. (B) Fat mass and lean mass determined by MRI at the end of the diet period.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a high-fat diet (HFD) for 10 weeks. (C and D) Liver mass and white fat (WF) mass.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a high-fat diet (HFD) for 10 weeks. (E) Respiratory exchange quotient, energy expenditure, and locomotor activity, detected in metabolic cages. Data are means ± SEM. (n=5-10) *P<0.05; **P<0.01; ***P<0.001 (2-way ANOVA coupled to Bonferroni's post tests).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a HFD for 10 weeks. (A) Representative H&E and oil red stained liver sections (Scale Bar: 50μm)",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a HFD for 10 weeks. (B) liver triglycerides (n=5-10).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a HFD for 10 weeks. (C) Plasma ALT at the end of the diet period.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a HFD for 10 weeks. (D) Glucose tolerance measured at the end of the diet period. Blood glucose concentration was measured in mice given an intraperitoneal glucose injection (1g/kg) after overnight fasting (n=5-10).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lyzs-Cre and p38γ/δLyzs-KO mice were fed a ND or a HFD for 10 weeks. (E) Basal blood glucose in overnight-fasted ND and HFD-fed Lyzs-Cre and p38γ/δLyzs-KO mice (n=5-10). Data are means ± SEM. (n=5-10) *P<0.05; **P<0.01; ***P<0.001 refers to p38γ/δLyzs-KO versus Lyzs-Cre; ##P<0.01; ###P<0.001 refers to ND versus HFD (2-way ANOVA coupled to Bonferroni's post tests or Newman-Keuls post test for liver triglycerides).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lethally irradiated WT mice were reconstituted with BM from Lyzs-Cre (Cx BMLyzs-Cre) or p38γ/δLyzs-KOmice (Cx BMp38γ/δLyzs-KO). Two months after the transplant, mice were fed the HFD for 10 weeks. (A) Freshly prepared CD45.2 whole BM mononuclear cells (2 × 107) were transplanted into lethally irradiated B6.SJL (CD45.1) mice, and engraftment by CD45.2 cells (%) was analyzed by antibody staining and FACS of peripheral blood and liverCD45+ cells. Charts show CD45.1 and CD45.2 expression in blood cells (left) and liver cells (right) isolated from transplanted mice (n = 3). Representative FACS dot plots of CD45.1 and CD45.2 expression are shown beneath the charts.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lethally irradiated WT mice were reconstituted with BM from Lyzs-Cre (Cx BM Lyzs-Cre) or p38γ/δLyzs-KO mice (Cx BM p38γ/δLyzs-KO). Two months after the transplant, mice were fed the HFD for 10 weeks. (B) Representative H&E and oil red-stained liver sections. Scale bar: 50 μm.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lethally irradiated WT mice were reconstituted with BM from Lyzs-Cre (Cx BMLyzs-Cre) or p38γ/δLyzs-KOmice (Cx BMp38γ/δLyzs-KO). Two months after the transplant, mice were fed the HFD for 10 weeks. (C) Livertriglyceride content.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lethally irradiated WT mice were reconstituted with BM from Lyzs-Cre (Cx BM Lyzs-Cre) or p38γ/δLyzs-KO mice (Cx BM p38γ/δLyzs-KO). Two months after the transplant, mice were fed the HFD for 10 weeks. (D) Plasma transaminase ALT activity.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Lethally irradiated WT mice were reconstituted with BM from Lyzs-Cre (Cx BMLyzs-Cre) or p38γ/δLyzs-KOmice (Cx BMp38γ/δLyzs-KO). Two months after the transplant, mice were fed the HFD for 10 weeks. (E) Fasted glucose, detected at the end of the diet period in overnight-fasted mice. Data are means ± SEM. (n=5-10) *P<0.05; **P<0.01; ***P<0.001 (2-way ANOVA coupled to Bonferroni's post tests).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "(A) Flow cytometry analysis of liver myeloid subsets (CD11b+ Gr-1high, CD11b+ Gr-1intermediate, CD11b+ Gr-1-) isolated from Lyzs-Cre and p38γ/δLyzs-KO mice fed a MCD for 3 weeks or HFD for 10 weeks. Representative dot plots are shown, and bar charts show the diet-induced increase in each population as a percentage of the total intra-hepatic CD11b+ leukocyte population. Myeloid infiltrating cells isolated from livers were sorted by FACS and stain with H&E. Representative cells were shown next to the appropriate myeloid subsets.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "(D and E) WT mice fed the MCD diet were i.v. injected with a 1:1 mix of DiO-labeled Lyzs-Cre neutrophil and DiD-labeled p38γ/δLyzs-KO neutrophils (6x106 cells in total; n=10). One hour after injection, liver-infiltrating neutrophils were assessed by flow cytometry (D) and fluorescence micrography on liver sections (E).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Osmotic minipumps containing saline or Ly6G antibody were implanted subcutaneously in Lyzs-Cre and p38γ/δLyzs-KO mice. These animals were fed a ND or MCD for 3 weeks. (A) Neutrophils and monocytes as a percentage of circulating leukocytes, measured in total blood.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Osmotic minipumps containing saline or Ly6G antibody were implanted subcutaneously in Lyzs-Cre and p38γ/δLyzs-KOmice. These animals were fed a ND or MCD for 3 weeks. (B) Representative H&E and oil red-stained liver sections after 3 weeks of treatment. Scale Bar: 50μm.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Osmotic minipumps containing saline or Ly6G antibody were implanted subcutaneously in Lyzs-Cre and p38γ/δLyzs-KO mice. These animals were fed a ND or MCD for 3 weeks. (C) Liver triglyceride and (D) plasma transaminase activity (ALT) at the end of the diet period.",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "Osmotic minipumps containing saline or Ly6G antibody were implanted subcutaneously in Lyzs-Cre and p38γ/δLyzs-KO mice. These animals were fed a ND or MCD for 3 weeks. (E) Total RNA was extracted from livers, and chemokine and cytokine mRNA levels were determined by qRT-PCR. mRNA expression was normalized to the amount of Gapdh mRNA. Data are means ± SEM. (n=5-10). *P<0.05; **P<0.01; ***P<0.001 (2-way ANOVA coupled to Bonferroni's post tests).",
    "ncbi_link": "Cre: 
Gapdh: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "(A, B and C) Plasma levels of 3-hydroxybutyrate in WT and p38γ/δ-/- (A), Lyzs-Cre and p38γ/δLyzs-KO mice (B) and Lyzs-Cre Ly6G Ab treated after MCD diet (C).",
    "ncbi_link": "Cre: 
Lyzs: 17105
p38γ: 29857"
  },
  {
    "caption": "(A) Rescue of growth phenotype. Wild-type (WT) or mdm10Δ cells were transformed with the empty plasmid pYX142 (). In addition, mdm10Δ cells were transformed with pYX142 encoding MDM10 or MCP3. Cells were grown to an OD600 of 1.0 and spotted on YPD or YPG plates in a 1:5 dilution series. Plates were incubated for growth at the indicated temperatures.",
    "ncbi_link": "MCP3: 
mdm10: 851223
MDM10: 851223"
  },
  {
    "caption": "(B) Over-expression of Mcp3 partially rescues the mitochondrial morphology defect in mdm10Δ cells. Cells described in (A) expressing mitochondrially targeted GFP (mtGFP) were analysed by fluorescence microscopy. Typical images (fluorescence and brightfield, BF) of the four different strains are shown (scale bar = 5 µm). The quantification shows the average percentage with standard deviation bars of three independent experiments (n=3; SD; *, p < 0.05 and as indicated) with at least 100 cells per experiment.",
    "ncbi_link": "Mcp3: 
mdm10: 851223"
  },
  {
    "caption": "(A) Respiratory chain super-complex levels are slightly restored by over-expression of Mcp3. Mitochondria isolated from the indicated strains were lysed in 1% digitonin and subjected to a 4-8% BN-PAGE. Proteins were analysed by immunodecoration with antibodies against either Cor1 of complex III or Cox2 of complex IV.",
    "ncbi_link": "Mcp3: "
  },
  {
    "caption": "(B) Assembly defects in TOM and TOB complexes in mdm10 cells are partially restored by Mcp3 over-expression. Mitochondria of the indicated cells were lysed in 1% digitonin and subjected to a 6-13% BN-PAGE and immunoblotting with antibodies against Tom40 (left) or Tob55 (right). The assembled TOM complex and an unassembled Tom40 species at ca. 100 kDa (arrowhead) are indicated as well as the TOB complex and an additional higher molecular weight species of the TOB complex (asterisk).",
    "ncbi_link": "Mcp3: 
mdm10: 851223"
  },
  {
    "caption": "(C) Over-expression of Mcp3 partially rescues the alterations in lipid composition of cells lacking Mdm10. Lipids were extracted from highly pure mitochondria isolated from the indicated cells and then analysed by mass spectrometry analysis. The level of each phospholipid species in wild-type mitochondria was set to 100% and the ERG/PL ratio to 1. Relative changes in mitochondria from other cells are presented. The mean with standard deviations of three biological repeats with two technical repeats for each (n=6; SD; *, p < 0.05) is given.",
    "ncbi_link": "Mcp3: 
Mdm10: 851223"
  },
  {
    "caption": "(D) Mcp3 rescues loss of Mdm12. Wild-type (WT) or mdm12Δ cells transformed with the empty plasmid pYX142 () or mdm12Δ cells over-expressing either Mcp3 or Mdm12 (as a control) were analysed at 30°C or 37°C by drop dilution assay on rich medium containing glycerol (YPG).",
    "ncbi_link": "Mcp3: 
Mdm12: 854153
mdm12: 854153"
  },
  {
    "caption": "(E) Mcp3 rescues loss of Mmm1. WT and mmm1Δ cells were transformed and analysed as described in (D).",
    "ncbi_link": "Mcp3: 
Mmm1: 850654
mmm1: 850654"
  },
  {
    "caption": "(F) Mcp3 rescues loss of Mdm34. WT and mdm34Δ cells were transformed and analysed as described in (D).",
    "ncbi_link": "Mcp3: 
Mdm34: 852654
mdm34: 852654"
  },
  {
    "caption": "(A) Growth phenotype of mcp3 cells. WT or mcp3∆ cells were grown to an OD600 of 1.0 in YPD medium and spotted on YPD or YPG plates in a 1:5 dilution series. Plates were incubated for growth at the indicated temperatures.",
    "ncbi_link": "mcp3: "
  },
  {
    "caption": "(B) mcp3 cells have normal mitochondrial morphology. WT and mcp3∆ cells expressing mitochondrially targeted GFP (mtGFP) were grown to mid-logarithmic phase then analysed by fluorescence microscopy. Typical images of the two different strains are shown (scale bar = 5 µm). The quantification of the depicted strains shows the average percentage with standard deviation bars of three independent experiments with at least 100 cells per experiment (n=3; SD; p as indicated).",
    "ncbi_link": "mcp3: "
  },
  {
    "caption": "(C, D) Loss of Mcp3 has no effect on the phospholipid composition of mitochondria. Highly-pure mitochondria were isolated from the indicated yeast cells. Lipids were extracted and then analysed by mass spectrometry analysis. The level of each phospholipid species in wild-type mitochondria was set to 100% and the ERG/PL ratio to 1. Relative changes in mitochondria from mcp3 cells are presented. The mean with standard deviations of three biological repeats with two technical repeats for each (n=6; SD) is given.",
    "ncbi_link": "Mcp3: 
mcp3: "
  },
  {
    "caption": "(E) Over-expression of Mcp3 leads to alterations of the tubular mitochondrial network. Wild-type cells expressing mitochondrially targeted GFP (mtGFP) were transformed with a plasmid over-expressing Mcp3 (MCP3) or an empty plasmid as control (). Cells were grown to mid-logarithmic phase and then analysed by fluorescence microscopy. Typical images of the two different strains are shown (scale bar = 5 µm).",
    "ncbi_link": "Mcp3: 
MCP3: "
  },
  {
    "caption": "(B) Internally tagged HA-Mcp3 is functional. mdm10∆ cells were transformed with the empty plasmid pYX142 () or pYX142 encoding Mdm10, Mcp3, or an internally HA-tagged Mcp3 (MDM10, MCP3, HA-MCP3). Cells were grown to an OD600 of 1.0 and spotted on YPG plates in a 1:5 dilution series. Plates were incubated for growth at 37°C for 4 days.",
    "ncbi_link": "Mcp3: 
MCP3: 
mdm10: 851223
Mdm10: 851223
MDM10: 851223"
  },
  {
    "caption": "(C) HA-Mcp3 is processed in vivo. Mitochondria isolated from mdm10∆ (∆) cells containing the empty plasmid or expressing HA-Mcp3 were analysed by SDS-PAGE and immunodecoration with antibodies against the indicated proteins. Two different bands are detectable in case of HA-Mcp3 (p, precursor; m, mature protein). The MOM protein Tom40 serves as loading control.",
    "ncbi_link": "Mcp3: 
mdm10: 851223"
  },
  {
    "caption": "(D) Mcp3 is a mitochondrial protein. Whole cell lysate (WCL) and fractions corresponding to cytosol (Cyt.), light microsomal fraction (ER) and mitochondria (Mito.) of mcp3∆ cells either containing the empty plasmid () or expressing HA-Mcp3 were analysed by SDS-PAGE and immunodecoration with antibodies against the HA-tag, the mitochondrial protein Tom70, a marker protein for the cytosol (Bmh1) and an ER marker protein (Erv2). m, mature protein.",
    "ncbi_link": "Mcp3: 
mcp3: "
  },
  {
    "caption": "(F) C-terminally tagged Mcp3-HA is located to mitochondria. A mitochondria enriched fraction (Mito.) and the post mitochondrial supernatant (PMS) of wild-type cells carrying the empty plasmid () or over-expressing the C-terminally HA-tagged Mcp3 (Mcp3-HA) were analysed by SDS-PAGE and immunodecortion with antibodies against the HA-Tag, the mitochondrial protein Tom40 and a marker protein for the cytosol (Hxk1). m, mature protein.",
    "ncbi_link": "Mcp3: "
  },
  {
    "caption": "(G) Mcp3 is membrane-embedded. Mitochondria isolated from mcp3Δ cells expressing HA-Mcp3 were left untreated (I, input) or subjected to alkaline extraction. The supernatant (SN) and pellet (P) fractions were analysed by SDS-PAGE and immunodecoration with antibodies against the indicated proteins. Tom20 an integral MOM proteins; Aco1, soluble matrix protein. m, mature protein.",
    "ncbi_link": "Mcp3: 
mcp3: "
  },
  {
    "caption": "(J) Mcp3 lacking either transmembrane domain fails to rescue loss of Mdm10. Wild-type cells carrying the empty plasmid (wt+) or mdm10∆ cells transformed with the empty plasmid () or plasmid encoding Mdm10, Mcp3, or Mcp3 lacking TMD1 or TMD2 (MDM10, MCP3, ΔTMD1, ΔTMD2) were grown to an OD600 of 1.0 and spotted on YPG plates in a 1:5 dilution series. Plates were incubated for growth at 37°C for 4 days.",
    "ncbi_link": "Mcp3: 
MCP3: 
Mdm10: 851223
mdm10: 851223
MDM10: 851223"
  },
  {
    "caption": "(K) Mcp3 lacking either of the two transmembrane domains is unstable. Crude mitochondria were obtained from wild-type cells containing an empty plasmid (Ø) or mcp3Δ cells (Δ) transformed with plasmid encoding Mcp3 or Mcp3 lacking TMD1 or TMD2 (MCP3, ΔTMD1, ΔTMD2). Samples were analysed by SDS-PAGE and immunodecoration with antibodies against Mcp3 and Tom20 as loading control.",
    "ncbi_link": "Mcp3: 
mcp3: 
MCP3: "
  },
  {
    "caption": "(B) Import of Mcp3 is dependent on the receptor Tom70. Mitochondria isolated from wild-type or tom70/71Δ cells were incubated with radiolabelled Mcp3 or pSu9-DHFR (as control) for the indicated time periods. After import mitochondria were reisolated and analysed by SDS-PAGE and autoradiography. p and m, precursor and mature forms, respectively. I, 20% of radiolabelled precursor protein used in each import reaction. Bands corresponding to the mature (m) form were quantified. Import into wild-type mitochondria after 15 min was set to 100%. The mean with standard deviations is depicted (n=3; SD).",
    "ncbi_link": "tom70: 855602
Tom70: 855602"
  },
  {
    "caption": "(C) Reduced steady state levels of HA-Mcp3 in cells lacking Tom70. Crude mitochondria isolated from the indicated cells were analysed by SDS-PAGE and immunodecoration with antibodies against the HA-tag, AAC as control substrate of Tom70, and Fis1 as a loading control. HA-Mcp3 levels were quantified in relation to Fis1 levels and the levels in WT cells were set to 100%. The bar diagram shows the mean with standard deviation (n=3; SD; *, p < 0.05).",
    "ncbi_link": "Mcp3: 
Tom70: 855602"
  },
  {
    "caption": "(D) Import of Mcp3 is dependent on Tom40. Mitochondria isolated from wild-type and tom4025 cells were incubated with radiolabelled Mcp3 for the indicated time periods. Next, mitochondria were reisolated and analysed by SDS-PAGE and autoradiography as described in (B). As a control Ugo1 was imported into the same mitochondria. Organelles were reisolated and analysed by BN-PAGE and autoradiography. The band corresponding to the Ugo1 dimer at around 150 kDa was quantified. The mean with standard deviation is shown (n=3; SD).",
    "ncbi_link": "Tom40: 
tom40: 855243"
  },
  {
    "caption": "(E) Steady state levels of HA-Mcp3 are lower in cells harbouring a mutant TOM40 allele. Crude mitochondria from wild-type and tom40-25 cells were obtained and analysed as described in (C). Immunodecoration was performed with antibodies against the HA-tag, Tom40, and Fis1 as loading control.",
    "ncbi_link": "Mcp3: 
TOM40: 855243
tom40: 855243"
  },
  {
    "caption": "(B) Mcp3 precursor binds to Tom22 in organello. Radiolabelled Mcp3 was incubated with mitochondria isolated from WT His-Tom22 containing cells. Mitochondria were pre-incubated with CCCP (40 µM) to halt import. After lysis with β-dodecyl maltoside samples were incubated with Ni-NTA beads. After washing bound proteins were eluted with sample buffer and analysed by SDS-PAGE and autoradiography. I, 5% of 35S-Mcp3 used; pel., 2% insoluble material after clarifying spin; sup., 2% of material incubated with Ni-NTA; n.b. 2% of non-bound material after binding to Ni-NTA; eluate, 100% of bound material.",
    "ncbi_link": "Tom22: 855592"
  },
  {
    "caption": "(A) Import of Mcp3 is dependent on the TIM23 complex. Mitochondria isolated from wild-type and tim23ts cells were incubated with radiolabelled Mcp3 for the indicated time periods. Further treatment and analysis (n=3; SD) was as described for Fig. 5D.",
    "ncbi_link": "tim23: 855751"
  },
  {
    "caption": "(B) Steady state levels of HA-Mcp3 are lower in cells harbouring a temperature sensitive TIM23 allele. Crude mitochondria were obtained at the non-permissive temperature from WT or tim23ts cells containing a plasmid expressing HA-Mcp3. Samples were analysed by SDS-PAGE and immunodecoration with antibodies against the HA-tag, the matrix proteins Mge1 and Yah1 as typical TIM23 substrates, Ugo1 and Fis1 as TIM23-independent substrates. HA-Mcp3 levels were quantified in relation to Fis1 levels. Levels in WT cells were set to 100%. The bar diagram shows the mean with standard deviation of six independent experiments (n=6; SD; **, p < 0.01).",
    "ncbi_link": "Mcp3: 
tim23: 855751
TIM23: 855751"
  },
  {
    "caption": "(D) Mcp3 is processed by Imp1/2. Single deletion strains of known mitochondrial proteases and peptidases were transformed with a plasmid expressing HA-Mcp3. Crude mitochondria were isolated and analysed by SDS-PAGE and immunodecoration with antibodies against the indicated proteins and the HA-epitope. Cox2, a known substrate of IMP; Tom70, a mitochondrial outer membrane protein.",
    "ncbi_link": "Mcp3: 
Imp1: 855182"
  },
  {
    "caption": "(E) C-terminally tagged Mcp3-HA is processed by Imp1. WT and imp1Δ cells were transformed with a plasmid expressing Mcp3-HA and further analysis was performed as described in (D).",
    "ncbi_link": "Mcp3: 
imp1: 855182
Imp1: 855182"
  },
  {
    "caption": "(F) Mcp3 is processed by Imp1/2 after in vitro import into mitochondria. Mitochondria isolated from WT, imp1Δ or imp2Δ strains were incubated with radiolabelled precursor of Mcp3 or pSu9-DHFR as control. Further treatment and analysis was as described in Fig. 5A.",
    "ncbi_link": "Imp1: 855182
imp1: 855182
imp2: 855051"
  },
  {
    "caption": "(G) Full-length Mcp3 precursor accumulates during import if IMP processing is abolished. Radiolabelled internally HA-tagged Mcp3 without (HA-Mcp3) or with mutation in the Imp1 cleavage site (D70G+HA) were incubated with mitochondria as in (F). After import samples were incubated with or without PK (20 µg/ml). Samples were analysed by SDS-PAGE and autoradiography.",
    "ncbi_link": "Mcp3: 
Imp1: 855182"
  },
  {
    "caption": "(A) Import of Mcp3 is mediated by the MIM complex. Mitochondria isolated from WT, mim1Δ, or mim2Δ cells were incubated with radiolabelled Mcp3 for the indicated time periods. After import mitochondria were reisolated and analysed by SDS-PAGE and autoradiography. Bands corresponding to the mature (m) form were quantified. Import after 15 min into wild-type mitochondria was set to 100%. The mean with standard deviations is depicted (n=3; SD). I, 20% of radiolabelled precursor protein used in each import reaction",
    "ncbi_link": "mim1: 854131
mim2: 850789"
  },
  {
    "caption": "B) Steady state levels of over-expressed HA-Mcp3 are reduced in cells lacking MIM subunits. Crude mitochondria were obtained from WT cells containing an empty plasmid (Ø) and from wild-type, mim1Δ or mim2Δ cells containing a plasmid encoded HA-Mcp3. Samples were analysed by SDS-PAGE and immunodecoration with antibodies against the HA-tag, Tom20 as MIM substrate and Fis1 as a loading control. HA-Mcp3 levels were quantified in relation to Fis1 levels. Levels in wild-type cells were set to 100%. The bar diagram shows the mean with standard deviation (n=3; SD; *, p < 0.05; **, p < 0.01).",
    "ncbi_link": "Mcp3: 
mim1: 854131
mim2: 850789"
  },
  {
    "caption": "ChIP-seq signal for EZH2 and H3K27me3 (left) at EMX2 and HOXB9 loci. ChIP-seq signal normalised to sequencing depth is shown. Tracks are scaled to be of the same height to make samples comparable. mRNA expression of EMX2 and HOXB9 (right) as detected by RNA-seq. Expression values represent mean ± SEM from three biological replicates. UT: untransformed, PN: pre-neoplastic, TR: transformed. TPM: transcripts per million.",
    "ncbi_link": "EMX2: 2018
HOXB9: 3219"
  },
  {
    "caption": "qRT-PCR showing the expression levels of EMX2 and HOXB9 in the indicated cells treated with EZH2i or a DMSO control for 12 days. Values represent mean ± SEM from three biological replicates. Two asterisks indicate p-value < 0.01 (one-tailed unpaired Student's t-test). UT: untransformed, TR: transformed.",
    "ncbi_link": "EMX2: 2018
HOXB9: 3219"
  },
  {
    "caption": "Expression levels of EMX2 and HOXB9 in primary human neural cells, as detected by RNA-seq. Data sourced from Brainseq2. Expression values represent mean ± SEM from four, twelve, one and five biological replicates of fetal astrocytes, mature astrocytes, neurons and oligodendrocytes, respectively. FPKM: fragments per kilobase of transcript per million.",
    "ncbi_link": "EMX2: 2018
HOXB9: 3219"
  },
  {
    "caption": "Expression levels of EMX2 and HOXB9 in 62 glioma cell lines. Data sourced from CCLE. Every dot represents a cell line. RPKM: reads per kilobase of transcript per million. In the boxplot, the top, middle and bottom box delimiters represent the 75th, 50th and 25th percentiles of the data, respectively. Top and bottom whiskers show the 75th percentile + 1.5*interquartile range and 25th percentile - 1.5*interquartile range, respectively.",
    "ncbi_link": "EMX2: 2018
HOXB9: 3219"
  },
  {
    "caption": "Quantification of EZH2 binding at EMX2, HOXB9 and GAPDH (negative control) promoters by ChIP-qPCR in M059K GBM cells. Values from two biological replicates are shown. Three asterisks indicate p-value < 0.001 of EZH2 samples relative to the negative control GAPDH (two-way ANOVA followed by pairwise comparisons using Holm-Sidak method). Ns: non-significant.",
    "ncbi_link": "GAPDH: 
EMX2: 2018
HOXB9: 3219"
  },
  {
    "caption": "Quantification of EMX2 levels by qRT-PCR in five different GBM cell lines upon treatment with 1μM, 3μM or 10μM of EZH2i for eight days, or a DMSO control. Values represent mean ± SEM from three technical replicates. The SEM is indicated to show reliability of the RT-PCR values, due to the low endogenous levels of EMX2. Two asterisks indicate p-value <0.01 comparing EZH2i- and DMSO-treated cells (Two-way ANOVA).",
    "ncbi_link": "EMX2: 2018"
  },
  {
    "caption": "Relationship between the extent of EMX2 upregulation induced by EZH2i and the DNA methylation level at the EMX2 promoter in GBM cell lines. Values for EMX2 upregulation are the fold-change in mRNA expression induced upon treatment with 10μM EZH2i (see: panel G), and are expressed relative to a DMSO control. Values represent mean ± SEM from three technical replicates. The SEM is indicated to show reliability of the RT-PCR values, due to the low endogenous levels of EMX2. Methylation values are averages of DNA methylation at CpGs across the promoter of EMX2 in GBM cell lines. All data sourced from the CCLE. The significance of the anti-correlation between mRNA levels and DNA methylation levels across cell lines is indicated (Spearman rank correlation).",
    "ncbi_link": "EMX2: 2018"
  },
  {
    "caption": "Heatmap visualizing the fold change in EMX2 expression as detected by qRT-PCR after treatment of the indicated PDX-derived (blue) and established cancer cell lines (black) with EZH2i for eight days. Values are from three technical replicates.",
    "ncbi_link": "EMX2: 2018"
  },
  {
    "caption": "Expression of EMX2 in normal brain and GBM patient samples. Data sourced from the Repository of Molecular Brain Neoplasia Data (REMBRANDT). Four asterisks indicate p-value < 0.0001 (two-tailed Mann Whitney U test). Bars represent median ± interquartile range. Values are expressed relative to the mean of normal brain samples. N: 21 for normal brain, 214 for GBM. Note that the extent of EMX2 repression in GBM patients is likely underestimated due to the possible presence of normal adjacent tissue in the analysed samples, and due to the intrinsic background noise of microarrays, which limits detection of truly silenced genes.",
    "ncbi_link": "EMX2: 2018"
  },
  {
    "caption": "Relative expression of HOX genes in normal brain and GBM patient samples as detected by microarray analysis. Data sourced from REMBRANDT. Values are expressed relative to the median of normal brain samples. In the boxplots, the top, middle and bottom box delimiters represent the 75th, 50th and 25th percentiles of the data, respectively. Top and bottom whiskers show the 75th percentile + 1.5*interquartile range and 25th percentile - 1.5*interquartile range, respectively. One asterisk indicates p-value <0.05 (two-tailed Mann Whitney U test corrected for multiple comparison using Holm's method). N: 21 for normal brain, 214 for GBM. Data was not available for HOXD8.",
    "ncbi_link": "HOXD8: 3234"
  },
  {
    "caption": "Covariance between EMX2 and EZH2 expression levels in GBM patient samples, as detected by microarray analysis. Data sourced from REMBRANDT. P-value and correlation coefficient (r) of the covariance are shown (Spearman rank correlation). Every dot is a patient. N: 214.",
    "ncbi_link": "EMX2: 2018
EZH2: 2146"
  },
  {
    "caption": "Expression levels of EMX2 (top) and EZH2 (bottom) in tumour or adjacent normal regions laser microdissected from human GBM tumours as detected by RNA-seq. Data sourced from the Ivy Glioblastoma Atlas. FPKM: fragments per kilobase of transcript per million. The significance of the differential expression in normal and tumour regions across patients is indicated (two-way ANOVA). Bars represent mean ± SEM. N: 3 regions sampled for each GBM tumour, 2, 3, 2, 3, 2, 3, 3 and 1 regions for normal tissue of patients 1-8, respectively.",
    "ncbi_link": "EMX2: 2018
EZH2: 2146"
  },
  {
    "caption": "Visualisation of EZH2 (green) and EMX2 mRNA (red) in a human GBM tumour by RNA FISH. Nuclei were counterstained with DAPI. Scale bar: 20 µm.",
    "ncbi_link": "EMX2: 2018
EZH2: 2146"
  },
  {
    "caption": "Expression of EMX2 (left) and EZH2 (right) in glioma patient samples, grouped according to tumour grade, as detected by RNA-seq. Data sourced from the Chinese Glioma Genome Atlas. Four asterisks indicate p-value < 0.0001 (Kruskal-Wallis test). Bars represent median ± interquartile range. N: 109 for grade II -, 72 for grade III, 144 for grade IV. RPKM: Reads per kilobase of transcript per million.",
    "ncbi_link": "EMX2: 2018
EZH2: 2146"
  },
  {
    "caption": "Proliferation assay examining the effect of EMX2 ectopic expression in U-87 MG and DBTRG-05MG GBM cells, RFP is used as a control. Values represent mean ± SEM from three biological replicates. The fold change in cell number after eight days of proliferation whilst expressing the exogenous protein is shown relative to an uninduced control. Two asterisks indicate p-value < 0.01 (one-tailed unpaired Student's t-test). Similar results were reported in [103] using other GBM cell lines.",
    "ncbi_link": "RFP: 
EMX2: 2018"
  },
  {
    "caption": "Transplantation assay comparing the growth kinetics of subcutaneous DBTRG-05MG-induced tumours expressing EMX2 at levels comparable to those expressed in normal cells, or expressing RFP as a control. Values represent mean ± SEM from six tumours. Three asterisks indicate p-value < 0.001 (two-tailed single sample Student's t-test). Similar results were obtained in an independent experiment using a distinct batch of transduced cells.",
    "ncbi_link": "RFP: 
EMX2: 2018"
  },
  {
    "caption": "MRI scans showing representative brain tumours six weeks post-injection of DBTRG-05MG cells expressing EMX2 or RFP. Axial anatomical scan and coronal signal intensity map indicate location of tumour in RFP control (yellow arrow). Contrast enhancement in post-contrast images indicates tumour blood brain barrier breakdown. Signal was not present in pre-contrast images. Images show the same MRI slice position between mice. Scale bar: 2mm. Quantification of brain tumour size in mice injected with EMX2- or RFP- expressing DBTRG-05MG cells. Values represent mean ± SEM from four control and three EMX2 tumours. Five mice per conditions were injected but three (one for RFP, and two for EMX2) had to be excluded from the study due to complications from the procedure.",
    "ncbi_link": "RFP: 
EMX2: 2018"
  },
  {
    "caption": "C PAM50 classifier results showing probabilities of pooled CTC-ITB-01 cells matching specific molecular breast cancer subtypes. Starting from lowest probability, CTC-ITB-01 was classified as 1.02% (s=2.5%) normal-like, 3.11% (s=6.6%) Basal-like, 13.11% (s=9.3%) ERBB2-positive, 16.77% (s=23.7%) luminal A, and 65.22% (s=16.6%) luminal B breast cancer subtype. Data was generated from n=3 replicates.",
    "ncbi_link": "ERBB2: 2064"
  },
  {
    "caption": "D PAM50 classifier results showing probabilities of the non-adherent and adherent CTC-ITB-01 fractions matching molecular subtypes. Selected bars are not visible due to extremely low probability (close to zero). Both fractions show greatest alignment with a luminal B subtype. Starting from lowest probability, the adherent fraction of CTC-ITB-01 was classified as 0% (±0%) normal-like, 6.22% (±9.0%) Basal-like, 17.85% (±8.6%) ERBB2-positive, 0% (s=0%) luminal A, and 75.92% (s=0.7%) luminal B breast cancer subtype. The suspension cell fraction of CTC-ITB-01 was classified as 2.04% (s=3.5%) normal-like, 0% (s=0%) Basal-like, 17.32% (s=9.7%) ERBB2-positive, 33.5% (s=23.8%) luminal A, and 68.67% (s=18.6%) luminal B breast cancer subtype, respectively. Data was generated from n=3 replicates.",
    "ncbi_link": "ERBB2: 2064"
  },
  {
    "caption": "B Stable knockdown of ER-alpha within CTC-ITB-01 cells was performed by using lentiviral transfer of non-targeted (scramble) or two different targeted shRNAs against ER-alpha. CTC-ITB-01 cells were seeded on 6-well plates. After 10 days cells were fixed and stained (left upper panel). Macroscopic photos are shown of the fixed cells (left lower panel), scale bar 200 µm. Western blots of lysates from knockdown of ER-alpha expression in CTC-ITB-01 cells transduced with the same amounts of lentiviral vectors were probed with the indicated antibodies. The extracts were obtained 72h after lentiviral transduction (right panel). Where indicated, western blots were visualized at long exposure (l.e.) and/or short exposure (s.e.).",
    "ncbi_link": "ER-alpha: 2099"
  },
  {
    "caption": "(a,b) Histograms of TDP43(WT)-EGFP (a) and TDP43A315T-EGFP (b) levels in individual neurons. Increasing amounts of DNA significantly shifted the distribution of log-transformed expression levels toward higher values (P 0.01 for all comparisons, two-sided Kolmogorov-Smirnov test). TDP43(WT)-EGFP, n = 1,287 neurons, with 290-342 cells per group; TDP43A315T-EGFP, n = 1,290, with 315-332 neurons per group. Values were pooled from 12 wells per condition, with experiments performed in duplicate.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(c) Automated fluorescence microscopy. Primary rodent cortical neurons were transfected with mApple and TDP43-EGFP, and survival was determined by repeated imaging at regular intervals. The last time at which the cell was noted to be alive (red arrows) was used as the time of death. Cells that survive the entire length of the experiment (cyan arrow) were censored. Scale bar, 25 μm.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(d,e) Cumulative risk of death over time for neurons transfected with EGFP, TDP43(WT)-EGFP (d) or TDP43A315T-neurons (e). Supplementary Table 1 lists the number of neurons, hazard ratios, 95% CI and P values for each condition, as determined by Cox proportional hazards analysis. Results were pooled from 12 wells per condition, with experiments performed in duplicate.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "f,g) Linear regression of calculated hazard ratio (± s.e.m.) as a function of total TDP43(WT)-EGFP (R2 = 0.9353) (f) or TDP43A315T-EGFP (R2 = 0.9574) (g) level. The total TDP43 level was determined by quantitative immunocytochemistry using TDP43-specific antibodies (Supplementary Fig. 3) and normalized to the amount of TDP43 in nontransfected neurons. Dashed lines, reference (HR = 1).",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(d) OPL. Primary cortical neurons were transfected with EGFP and TDP43(WT)-Dendra2, photoconverted then imaged by AFM. Dead cells (arrows) were excluded at the time of death. Pre, before photoconversion. (e) The half-life of TDP43(WT)-Dendra2 was determined by fitting a first-order exponential curve to the data (R2 = 0.9558). (f) Including cells with aggregates prolonged TDP43(WT)-Dendra2 half-life (pink line, R2 = 0.9003; *P 0.0001, F 15.34, extra sum-of-squares F-test). Excluding cells that died over the 36-h experiment also prolonged half-life (cyan line, R2 = 0.7171; **P 0.0001, extra sum-of-squares F-test). Error bars represent s.e.m. Values were pooled from eight wells per condition, with experiments performed in quadruplicate.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(a) Scatter plot depicting half-life measurements for individual cells expressing TDP43(WT)-Dendra2 (cyan, n = 206) and TDP43A315T-Dendra2 (red, n = 251). *P = 0.0029, U = 11,797, Mann-Whitney test.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "b) Probability density plot for single-cell half-life measurements, demonstrating a reduced half-life of TDP43A315T-Dendra2 (red, n = 251), compared to TDP43(WT)-Dendra2 (cyan, n = 206; **P = 0.0007, two-sided Kolmogorov-Smirnov test). Values were pooled from eight wells per condition, with experiments performed in quadruplicate.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(c,d) Probability density plots of single-cell half-life measurements for TDP43(WT)-Dendra2 (c) and TDP43A315T-Dendra2 (d). At 0.5 μM, all three of the compounds significantly reduced TDP43(WT)-Dendra2 half-life compared to vehicle control (DMSO, n = 110; FPZ, n = 96, f* P = 1 × 10−4; MTM, n = 129, m* P = 2 × 10−7; NCP, n = 111, n* P = 2 × 10−5, two-sided Kolmogorov-Smirnov test). The compounds also reduced TDP43A315T-Dendra2 half-life, in comparison to vehicle control (DMSO, n = 120; FPZ, n = 155, f* P = 2 × 10−9; MTM, n = 152, m* P = 0.004; NCP, n = 111, n* P = 0.005, two-sided Kolmogorov-Smirnov test). Colored hash marks represent values from individual neurons in b-d. Values were obtained from eight wells per condition, with experiments performed in triplicate.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(e) The change in red fluorescence intensity over time was used to calculate LC3-Dendra2 half-life, as in Figure 2 (DMSO, R2 = 0.7333; Beclin, R2 = 0.6968, FPZ, R2 = 0.8752; MTM, R2 = 0.8447; NCP, R2 = 0.8357; *P 0.0001 for global trend, F = 12.6, extra sum-of-squares F-test). Error bars represent s.e.m. (",
    "ncbi_link": "Beclin: "
  },
  {
    "caption": ". (f) The median single-cell half-life of LC3-Dendra2 was significantly reduced by beclin expression or treatment with 0.5 μM NCP, MTM or FPZ (*P 0.01, **P 0.001, Kruskal Wallis statistic = 52.56, Kruskal-Wallis with Dunn's test).",
    "ncbi_link": "beclin: "
  },
  {
    "caption": "(g) Probability density plot of LC3-Dendra2 half-life measurements from individual neurons treated with vehicle control (DMSO, n = 140), NCP (n = 128), MTM (n = 91), FPZ (n = 77) or those expressing beclin (n = 101). n*, P = 6 × 10−4; m*, P = 1 × 10−10; f*, P = 5 × 10−9; b*, P = 2 × 10−3; two-sided Kolmogorov-Smirnov test). Colored hash marks represent values from individual neurons. Values were pooled from eight wells per condition, with experiments performed in triplicate.",
    "ncbi_link": "beclin: "
  },
  {
    "caption": "(a) FPZ (n = 490) and MTM (n = 580) but not NCP (n = 523) lowered total TDP43(WT)-EGFP levels in comparison to vehicle (DMSO, n = 1,007).",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(b) Histogram of normalized, log-transformed TDP43(WT)-EGFP levels.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(c) Each compound also reduced TDP43A315T-EGFP levels (DMSO, n = 983; FPZ, n = 550; MTM, n = 542; NCP, n = 493).",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(d) Histogram of single-cell TDP43(A315T)-EGFP levels. Asterisks in b and d denote median values for cells exposed to vehicle (gray), FPZ (green), MTM (blue) or NCP (purple). For FPZ, MTM and NCP versus DMSO in a and d, P 1 × 10−3 by two-sided Kolmogorov-Smirnov test.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "e) No compound reduced TDP43(WT)-EGFP inclusions 48 h after transfection (DMSO, n = 360; FPZ, n = 194; MTM, n = 234; NCP, n = 203).",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(f) FPZ and MTM but not NCP reduced TDP43A315T-EGFP inclusions at 48 h (DMSO, n = 327; FPZ, n = 226; MTM, n = 262; NCP, n = 253). (g) No compound affected TDP43(WT)-EGFP localization 24 h after transfection (DMSO, n = 256; FPZ, n = 212; MTM, n = 250; NCP, n = 241). (h,i) Each compound (h) prevented TDP43A315T-EGFP cytoplasmic mislocalization (DMSO, n = 233; FPZ, n = 268; MTM, n = 263; NCP, n = 270) and reduced cytoplasmic TDP43(A315T)-EGFP levels (DMSO, n = 125; FPZ, n = 102; MTM, n = 121; NCP, n = 144. *P 0.05; NS, P > 0.05) (i). For a, c and e-i, *P 0.05; nonsignificant (NS), P > 0.05, one-way ANOVA with Dunnett's test. Error bars represent s.e.m. Values in a-d were pooled from 8-12 wells per condition from six experiments, values in e-h were pooled from eight wells per condition from three experiments, and values in i were pooled from five wells per condition from two experiments.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "(a,b) Primary neurons transfected with TDP43(WT)-EGFP (a) or TDP43A315T-EGFP (b) were treated with autophagy inducers and survival determined by AFM. Data were obtained from eight wells per condition, with experiments performed in triplicate. Supplementary Table 2 lists the number of neurons per condition, hazard ratios, 95% CI and P values, as determined by Cox hazards analysis. (c) Autophagic induction improved survival in TDP43M337V HB9-positive human iPSC-derived MNs. (d) FPZ and MTM also reduced the risk of death in MAP2-positive human iPSC-derived MNs Values in c and d were pooled from 18 wells per condition, with experiments performed in triplicate. (e) Astrocytes differentiated from human iPSCs exhibit mutant TDP43-related toxicity that is mitigated by FPZ and MTM. Values were pooled from 18 wells per condition, performed in triplicate. Supplementary Table 3 lists the number of human iPSC-derived neurons and astrocytes per condition, hazard ratios, 95% CI and P values, as determined by Cox hazards analysis.",
    "ncbi_link": "TDP43: 23435"
  },
  {
    "caption": "U2OS cells modified to expressed endogenous GFP-tagged ATG2A (green) were grown in complete media (CM) or starved (EBSS) for 2 h before fixation and immunostaining with antibodies against ATG2B (red) and LC3B (magenta) and analysed by confocal microscopy. Arrows mark ATG2A/LC3B/ATG2B positive structures. Scale bar 10µm. (B-D) Cells were treated as in (A) and stained with anti-WIPI2 (red) or (C) anti-ATG16L1 (red) or (D) GABARAP-L1 (red). Arrows mark structures of interest. Scale bar 10µm. ",
    "ncbi_link": "GFP: 
ATG2A: 23130"
  },
  {
    "caption": "U2OS WT or U2OS GFP-ATG2A knock-in (KI) cells were grown in CM or starvation media for 2 h, lysed and incubated with anti-GFP nanobody beads coupled to agarose to immunoprecipitate (IP) GFP-ATG2A. IP samples and 2% input lysates were run on 4-12% gradient gel and processed for western blotting. Anti-ATG2A, anti-WIPI4 and anti-LC3B, anti-GABARAP (pan) were used to probe for the presence/absence of autophagy proteins in the immunoprecipitated samples. p-p70S6K (T389) was used as a marker for starved cells and total p70S6K as loading control.",
    "ncbi_link": "GFP: 
ATG2A: 23130"
  },
  {
    "caption": "Myc-tagged ATG2A-wild type (WT) and ATG2A-mLIR (orange) were co-expressed with GFP-alone, GFP-LC3B or GFP-GABARAP in HEK293T cells, lysed and anti-GFP nanobodies coupled to agarose were used to immunoprecipitate GFP-tagged proteins. Samples were subjected to western blotting and probed for the presence of Myc-ATG2A in immunoprecipitated samples. Anti-p62/SQSTM1 was used as an internal control for the immunoprecipitated samples.   As in (B) but using Myc-tagged ATG2B-WT or ATG2B-mLIR (orange) co-expressed with GFP-alone, GFP-LC3B or GFP-GABARAP. Samples were subjected to western blotting and probed for the presence of Myc-ATG2B in immunoprecipitated samples. Anti-p62/SQSTM1 was used as an internal control for the immunoprecipitated samples.   ",
    "ncbi_link": "GFP: 
Myc: 
ATG2A: 23130
ATG2B: 55102
GABARAP: 11337
LC3B: 81631"
  },
  {
    "caption": "HA-tagged ATG2A-WT, -mLIR (orange) and -mYFS (YFS/AAA; purple) were stably expressed in U2OS ATG2A/B double knock-out cells using retrovirus transduction. Cells were transfected with GFP-GABARAP and 24 h later grown in complete medium (CM) or starved for 2 h (EBSS). Cells were lysed and anti-HA beads were used to immunoprecipitate HA-tagged ATG2A and processed for western blot. Blots were then probed with antibodies against HA-tag (ATG2A), anti-WIPI4, and anti-GFP for the presence/absence in immunoprecipitated samples. All blots are representative of at least n=3 independent experiments.   Quantification of WIPI4 and GFP-GABARAP-ii co-precipitation with HA-ATG2A from (D). bands were normalized against HA-ATG2A immunoprecipitate and expressed as a fold change compared to HA-ATG2A-WT (complete media; CM). Each symbol represents an independent experiment (n=3) and error bars mean ± SD.   ",
    "ncbi_link": "GFP: 
HA: 
ATG2A: 23130
GABARAP: 11337"
  },
  {
    "caption": "ATG2A/B do8uble knock-out cells (DKO) stably expressing HA-tagged ATG2A-WT, -mLIR (orange) or -mYFS (YFS/AAA; purple) were transfected with GFP-GABARAP and 24 h later grown in complete medium (CM) or starved for 2 h (EBSS). Cells were lysed and GFP-GABARAP was immunoprecipitated using anti-GFP trap beads. Samples were processed for western blot and probed with anti-HA-tag (ATG2A), anti-WIPI4, and anti-GFP for their presence/absence in immunoprecipitated samples. All blots are representative of at least n=3 independent experiments.   Quantification of HA-ATG2A and WIPI4 co-precipitation with GFP-GABARAP from (F). Results were expressed as a fold change compared to HA-ATG2A-WT (complete media; CM). Each symbol represents an independent experiment (n=3) with error bars mean ± SD.   ",
    "ncbi_link": "HA: 
ATG2A: 23130
GABARAP: 11337"
  },
  {
    "caption": "GFP alone, GFP-GABARAP or GFP-GABARAP with increasing concentrations of mCherry-WIPI4 were expressed in HEK293T cells for 24 h, lysed and GFP-trap beads used to immunoprecipitate GFP alone or GFP-GABARAP. Samples were then probed with antibodies to detect endogenous ATG2A or ATG2B in immunoprecipitated samples. Blots are representative of n=3 independent experiments.   Quantification of ATG2A (green line, round symbols) and ATG2B (grey line and squares) co-precipitation with GFP-GABARAP in the presence of increasing concentrations of mCherry-WIPI4 from (H). Co-precipitation was normalised to GFP-GABARAP alone. Line and error bars are mean ±SD of n=3 independent experiments.   ",
    "ncbi_link": "GFP: 
mCherry: 
GABARAP: 11337
WIPI4: 11152"
  },
  {
    "caption": "U2OS ATG2A/B double knock-out (DKO) CRISPR/Cas9 cells stably expressing Tandem tagged LC3B (mCherry-GFP-LC3B) were retrovirally transduced to express vector, or HA-tagged ATG2A-WT, -mLIR (FCIL/AAAA) or -mYFS (YFS/AAA). Cells were grown in complete medium (CM) or starved for 2 h (EBSS) or treated with CM plus BafilomycinA1 (200nM, 4 h), fixed and analysed by confocal microscopy. Merged images of GFP (green) and mCherry (red) channels show the presence of autophagosomes/phagophores (GFP and mCherry positive, yellow puncta) or autolysosomes (mCherry only, red puncta) Scale bar 10µm. Images are representative of n=3 independent experiments.",
    "ncbi_link": "CRISPR: 
GFP: 
HA: 
mCherry: 
ATG2A: 23130
LC3B: 81631
Cas9: 901176"
  },
  {
    "caption": "U2OS ATG2A/B DKO cells reconstituted with vector only, HA-ATG2A-WT, -mLIR and -mYFS were stimulated with complete medium, (CM), 2 h starvation (EBSS) or 4 h BafilomycinA1 (BafA1, 200nM), lysed in total cell lysis buffer and subjected to western blot analysis. Blots were probed for the presence of HA-tag (ATG2A), p62/SQSTM1, LC3B, pan-GABARAP (GABARAP, GABARAP-L1 and GABARAP-L2) and vinculin (loading control).",
    "ncbi_link": "HA: 
ATG2A: 23130"
  },
  {
    "caption": "U2OS ATG2A/B DKO cells reconstituted with vector only, HA-ATG2A-WT, -mLIR and -mYFS were stimulated with complete medium, (CM), 4 h starvation (EBSS) plus BafilomycinA1 (BafA1, 200nM) treatment. Cells were centrifuged and resuspended in PBS digitonin, spun, washed and the membrane fractions incubated with proteinase K with and without 0.1% TritonX-100. Sampels were then subjected to western blotting using anti-p62/SQSTM1 and anti-HA (ATG2A) antibodies. Percentage p62/SQSTM1 remaining was calculated using densitometry analysis. Blots are representative of n=3 independent experiments.",
    "ncbi_link": "HA: 
ATG2A: 23130"
  },
  {
    "caption": "U2OS ATG2A/B DKO cells reconstituted with vector only, HA-ATG2A-WT, -mLIR and -mYFS and stably expressing GFP-Syntaxin17 (STX17) were stimulated starvation (EBSS) plus BafilomycinA1 (BafA1, 200nM) for 4 hours to stimulate autophagosome generation and prevent their degradation in the lysosome. Cells were fixed and immune-stained for LC3B (magenta). DAPI was included (blue) to mark the DNA/nucleus. Confocal analysis of LC3B and GFP-STX17 (green) localization was performed. Closed arrows (ATG2A/B DKO and DKO + ATG2A mLIR) highlight aggregate structures. Open arrows (DKO + ATG2A-WT and ATG2A-mYFS) highlight STX17/LC3B positive vesicles. Scale bar 10µm.   Quantification of (C) expressed as a percentage of cells with STX17/LC3B positive vesicles. Each symbol represents a single field of cells with 5-10 cells per field. A total of 300-600 cells were analysed over n=3 independent experiments. Data is shown as mean ± SD.   ",
    "ncbi_link": "GFP: 
HA: 
ATG2A: 23130
STX17: 55014
Syntaxin17: 55014"
  },
  {
    "caption": "(A-C) U2OS ATG2A/B double knock out (DKO) cells or DKO reconstituted with ATG2A-WT, -mLIR (FCIL/AAAA) or -mYFS (YFS/AAA) were starved for 2 h, fixed and stained for LC3B (green) or WIPI2 (magenta), (B) ATG9A (magenta) or (C) GABARAP (Magenta) and imaged using a Zeiss 880 Airyscan super-resolution confocal microscope. Images are representatives of n=3 independent experiments. Scale bars 10µm.",
    "ncbi_link": "ATG2A: 23130"
  },
  {
    "caption": "Transmission electron micrographs of ATG2A/B DKO cells (upper left), DKO + ATG2A-WT (upper right), DKO+ ATG2A-mLIR (lower left) and DKO+ATG2A-mYFS( lower right) starved (EBSS) for 2 h. Clustered small vesicles (open arrowheads; DKO and DKO-mLIR) and autophagosomes (closed arrow heads, DKO+ATG2A-WT and -mYFS) indicated. Images are representative of n=3 independent experiments. Scale bars 500nm. ER= endoplasmic reticulum; N = Nucleus; Mt = Mitochondria; G = Golgi; AP = Autophagosome.",
    "ncbi_link": "ATG2A: 23130"
  },
  {
    "caption": "A) GST pulldown used to analyse TBC1D14 interactors. Recombinant GST or GST-TBC1D14 was incubated with or without HEK 293A lysate. Bound proteins were eluted from the beads using Laemmli sample buffer and subjected to SDS-PAGE, with visible bands being excised from the gel and analysed by mass spectrometry.",
    "ncbi_link": "TBC1D14: 57533"
  },
  {
    "caption": "C) Lysates of cells expressing GFP or GFP-TRAPPC3 were subjected to IP with GFP-Trap, and then immunoblotted for TRAPPC4, GFP and TBC1D14.",
    "ncbi_link": "TRAPPC3: 27095"
  },
  {
    "caption": "A) HEK293A cells transfected with GFP (upper panels) or GFP-TBC1D14 (lower panels) (green) were labelled with anti-RAB11A (red) and anti-RAB1B (white, blue in merge) antibodies. Arrows depict transfected cells. Inset: GFP-TBC1D14 transfected cell showing triple co-localisation between GFP-TBC1D14, RAB11A and RAB1B (white arrows) and double co-localisation between GFP-TBC1D14 and RAB11A (yellow arrows).",
    "ncbi_link": "TBC1D14: 57533"
  },
  {
    "caption": "A) HEK293A cells expressing GFP, GFP-TBC1D14 224-669 or GFP-TBR were treated in duplicate with EBSS, EBSS plus 100 nM BafA1 or not for two hours, lysed and subjected to immunoblotting for LC3B, tubulin and GFP. The amount of LC3B/tubulin for each condition from three independent experiments is shown on the bar graph, ±s.e.m. * p<0.05, ** p<0.01, one way ANOVA with Sidak's multiple comparison test.",
    "ncbi_link": "TBC1D14: 57533"
  },
  {
    "caption": "C) siRNA transfected control cells (RISC Free) or TRAPPC8 knockdown (TRAPPC8) (1x10cm plate per condition) were lysed in TNTE and used in pulldown assays with immobilised recombinant GST or GST-TBR. Bound proteins were subjected to immunoblot analysis using TRAPPC8, TRAPPC4 and tubulin antibodies. Ponceau staining was used to verify loading of the GST fusion proteins (GST-TBR indicated with arrowhead). The bar chart expresses the relative amount of TRAPPC4 isolated from siTRAPPC8 compared to siRISC Free control cells from three independent experiments, error bars are ± s.e.m. ** p<0.01, unpaired T-test",
    "ncbi_link": "TRAPPC8: 22878"
  },
  {
    "caption": "D) HEK293T cells stably depleted of TRAPPC8 (shC8) or not (shCtrl) were transfected with constructs encoding GFP or GFP-TRAPPC3 and subjected to GFP Trap IP. Precipitated proteins were immunoblotted for GFP, TRAPPC4 and TRAPPC8. Bar chart: the amount of TRAPPC4 isolated was normalised to the amount of GFP-TRAPPC3 precipitated from three independent experiments and plotted ± s.e.m., ns = non-significant, unpaired T-test.",
    "ncbi_link": "TRAPPC3: 27095
TRAPPC8: 22878"
  },
  {
    "caption": "A) HEK293A cells treated with transiently transfected with RISC free control siRNA or siRNA duplexes directed against TRAPPC8 and RAB11A and B (knockdown confirmed by immunoblot analysis) were fed with Alexa-647 Transferrin for 15 minutes in full medium, and the fluorescent transferrin chased out for the indicated time periods. At the end of the time course, cells were trypsinised, fixed and the Alexa-647 fluorescence analysed by flow cytometry. Results are plotted as percentage of transferrin fluorescence at t=0 for the RISC free control cells, expressed as the mean of three independent experiments ± s.e.m.",
    "ncbi_link": "RAB11A: 8766
TRAPPC8: 22878"
  },
  {
    "caption": "B) Cells transiently transfected with RISC Free control siRNA, or siRNA duplexes directed against TRAPPC8 or RAB1A and B were stained for the cis-Golgi markers GM130 or RAB1B and analysed by confocal microscopy. Scale bars = 20 μm in main panels, 10 μm in inset panels. Bar graph: > 100 cells per siRNA were scored for fragmented or normal juxtanuclear Golgi stacks from three independent experiments. Error bars ± s.e.m., * p<0.05, ** p<0.01, one way ANOVA with Sidak's multiple comparison test.",
    "ncbi_link": "RAB1A: 5861
TRAPPC8: 22878"
  },
  {
    "caption": "C) HeLa C1 cells transiently transfected with RISC free control siRNA or siRNA duplexes directed against TRAPPC8 or RAB1A and B (knockdown confirmed by immunoblot analysis), were treated with D/D solubiliser for the indicated time periods, trypsinised, fixed and their GFP content analysed by flow cytometry. The line graph shows the GFP fluorescence as a percentage of t=0, ± s.e.m. from three independent experiments.",
    "ncbi_link": "RAB1A: 5861
TRAPPC8: 22878"
  },
  {
    "caption": "C) HEK293A cells transiently transfected with RISC Free siRNA or siRNA against TRAPPC8 were stained for RAB1B (green) and ATG9 using hamster anti-ATG9 (red) and imaged using confocal microscopy.",
    "ncbi_link": "TRAPPC8: 22878"
  },
  {
    "caption": "A) Cells depleted of ULK1 (siULK1) or not (RISC Free) were transfected with GFP or GFP-TBR (green), starved (EBSS) or not (-EBSS) and stained for ATG9 using hamster anti-ATG9 (red). Arrows indicate transfected cells. Western blot indicates ULK1 knockdown. Scale bars = 20 μm.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "B) Cells depleted of ULK1 (siULK1) or not (RISC Free) were transfected with myc-RAB1B or myc-RAB1B (S22N) (green), starved (EBSS) or not (-EBSS) and stained for ATG9 using hamster anti-ATG9 (red) Arrows indicate transfected cells. Western blot indicates ULK1 knockdown. Scale bars = 20 μm.",
    "ncbi_link": "RAB1B: 81876
ULK1: 8408"
  },
  {
    "caption": "(F-H) Primary cortical neurons: Cortical neurons were infected with control lentivirus (empty vector) or lentivirus expressing FLAG-tagged CA10, and cell lysates subjected to immunoprecipitation for neurexin and heparinase treatment. (F) Samples were analyzed by immunoblotting using antibodies against neurexins, 3G10 (for the HS stub) and FLAG (for CA10). Stars indicate non-neurexin bands (see results). (G) Quantification of low molecular weight neurexin (LMW; white arrowhead) in relation to total neurexin amounts [upper band (line) + LMW]. Data shown as mean ±SEM (n=3 independent experiments); *, p< 0.05 by 2-way ANOVA and Holm-Sidak tests. (H) Quantification of the 3G10 signal normalized to the signal of the corresponding neurexin band. Data shown as mean ±SEM of biological replicates. *, p< 0.05 by 2-way ANOVA and Holm-Sidak tests (n=3).",
    "ncbi_link": "FLAG: 
CA10: 72605"
  },
  {
    "caption": "(B) Representative immunoblot of the indicated proteins harvested from HEK293 cell media and subjected to heparinase treatment ('Heps'). Samples were analyzed by reducing SDS/PAGE and immunoblotting with antibodies against Fc (for Nrxn1β), the 3G10 epitope (for the HS stub) and V5 (for CA10). Input samples were analyzed separately for CA10 to ensure equal expression (lower panel). (C) Quantification of the 3G10 epitope signal, normalized to Fc (Nrxn1β). Data shown are mean ±SEM of 3 independent replicates. *, p< 0.05; by Mann-Whitney tests comparing each Nrxn1 mutant with and without CA10 (n=3). No significance difference was observed for S&T>G (p=0.1143), GIGG (p=0.9714) or DIRR (p=0.4857) variants. ",
    "ncbi_link": "Nrxn1: 9378"
  },
  {
    "caption": "(E) representative immunoblots analyzed using antibodies against the Fc-tag (for Nrxn1β-Fc) the 3G10 epitope (for the HS stub) and V5 (CA10-V5), as indicated. CA10 in input samples is shown for demonstration of equal expression. (F, Quantification of the 3G10 epitope signal normalized to Fc (for Nrxn1β-Fc) signals, Data shown are mean ±SEM of 3 biological replicates. *, p< 0.05; ***, p<0.001 by 2-way ANOVA and Holm-Sidak tests.",
    "ncbi_link": "CA10: 56934"
  },
  {
    "caption": "(A-B) Cell surface binding to endogenous neurexins. (A) Recombinant Fc-tagged LRRTM2 was added to day 10 hippocampal neurons expressing CA10 or control (empty vector) by lentiviral transduction. Surface-bound protein was quantified as the Fc signal of and normalized to a staining for endogenous neurexin (n=4 cultures; three fields imaged and averaged per well). Scatchard analysis for LRRTM2 revealed an apparent Kd of 29.5 nM and a Bmax of 0.49 nM for control and Kd 35.3 nM, Bmax 0.28 nM upon expression of CA10; significant (p=0.0006) by non-linear regression. Data shown as mean ± SEM of biological replicates (n=4). (B) Increasing amounts of recombinant, Fc-tagged Nlgn1 was added to immature hippocampal neurons expressing CA10 or control (empty vector) by lentiviral transduction, and analyzed as in (A). The apparent Kd for Nlgn1 was 186 nM and Bmax 1.65 nM for control and Kd 223 nM, Bmax 1.49 nM when CA10 was overexpressed. The difference was not significant (p=0.20) by non-linear regression. Data shown as mean ± SEM of biological replicates (n=4).",
    "ncbi_link": "CA10: 72605"
  },
  {
    "caption": "(C-D) Artificial synapse formation assays. (C) Confocal images of hippocampal neurons transduced to express CA10-FLAG or control (empty vector) and co-cultured with HEK293 cells expressing GFP, Nlgn1-YFP, LRRTM2-YFP or TrkC-YFP. Cells were stained with antibodies against the synaptic marker SV2 (red) and somatodendritic MAP2 (blue); GFP/YFP is shown in green. Scale bar 20 μm. (D) Quantifications of SV2 signal overlapping GFP/YFP-positive cells. Data shown as means ±SEM with the n, reflecting number of independent cover slips analyzed, indicated in each bar with the total number of cells imaged in parenthesis. Comparisons were made by one-way ANOVA with Holm-Sidak's posthoc test for multiple comparisons between the indicated groups (GFP condition was omitted from analysis due to unequal variance; ***, p<0.001.",
    "ncbi_link": "FLAG: 
GFP: 
LRRTM2: 
Nlgn1: 
TrkC: 
YFP: 
CA10: 72605"
  },
  {
    "caption": "(E-F) Analysis of cerebellin(Cbln)-induced artificial synapse formation. (E) Confocal images of hippocampal neurons transduced to express CA10-FLAG or control (empty vector) and co-cultured exposed to anti-V5-coupled beads pre-incubated with recombinant V5-tagged Cbln1 or empty anti-V5 beads. Cells were stained with antibodies against the synaptic marker synapsin (green), somatodendritic MAP2 (blue); beads are colored red and indicated by arrowheads. Scale bar 10 μm. (F) Quantifications of the synapsin signal overlapping red beads. Data shown as means ±SEM (n=3 independent experiments, each data point corresponding to 58-171 analyzed beads), with comparisons made by two-way ANOVA with Holm-Sidak's posthoc test for multiple comparisons between the indicated groups.",
    "ncbi_link": "FLAG: 
CA10: 72605"
  },
  {
    "caption": " C Wild-type and tel1∆ strains expressing a fully functional Top1-HA tagged protein were arrested in G1 with α-factor (αf) and released into YEPD supplemented with CPT (50 μM). Western blot with anti-HA antibodies (top) and Coomassie staining (bottom) of protein extracts prepared at the indicated time points ",
    "ncbi_link": "tel1: 852190"
  },
  {
    "caption": "(B) Western blot analysis of supernatants after protein production of WT and C94S mutant long mouse DNGR-1 ECD proteins under reducing and non-reducing conditions. C94S mutant-containing supernatant was 200x concentrated before analysis.",
    "ncbi_link": "DNGR-1: 232414"
  },
  {
    "caption": "(B and C) B3Z-Syk reporter cells expressing indicated mutant or WT DNGR-1 receptors (mouse, long isoform) were incubated with UV-irradiated 293T cells (ratio dead:reporter cells is indicated), or with plate-bound anti-DNGR-1 antibody or medium alone at 37°C overnight. Activation of the NFAT reporter was measured at the end of the incubation period. Data are plotted as mean ± SD of experimental duplicates. One representative of three experiments is shown.",
    "ncbi_link": "DNGR-1: 232414"
  },
  {
    "caption": "(D) Phoenix cells expressing indicated mutant or WT DNGR-1 proteins (mouse, long isoform) were treated with F-actin, F-actin buffer, anti-DNGR-1 antibody or isotype-matched antibody of irrelevant specificity for 45 minutes, fixed in PFA, surface-stained for DNGR-1 and analyzed by flow cytometry. One representative of three experiments is shown.",
    "ncbi_link": "DNGR-1: 232414"
  },
  {
    "caption": "(A) DNGR-1 KO MuTu DCs were transduced to express indicated DNGR-1 proteins, FACS-sorted and expanded. Surface (left panel) and total (right panel) DNGR-1 expression was determined by flow cytometry.",
    "ncbi_link": "DNGR-1: 232414"
  },
  {
    "caption": "(B and C) Ovalbumin-expressing mouse embryonic fibroblasts (bm1 T OVA MEFs) were UV-irradiated, left to undergo secondary necrosis and incubated overnight with MuTu cells transduced with indicated WT or mutant DNGR-1 proteins or an empty-vector control (ratio dead cells:MuTu cells is indicated) and OVA-specific pre-activated OT-I CD8+ T-lymphocytes. The amount of IFNγ accumulating in the culture medium was assessed using ELISA. One representative of two (B) or four (C) experiments is shown.",
    "ncbi_link": "DNGR-1: 232414"
  },
  {
    "caption": "(a) The Kaplan-Meier survival curves for KRas;Atg5+/+ (n=12), KRas;Atg5fl/+ (n=19) and KRas;Atg5fl/fl (n=18) littermate mice injected intranasally with AdCre (2.5 × 107 p.f.u.). P0.01 (log-rank test) between the KRas;Atg5fl/fl cohort and controls",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(b) Western blot analysis for Atg5, LC3I and LC3II and p62 in purified primary lung tumour cells. Representative data are shown for tumour cells isolated from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 18 weeks after AdCre inhalation. β-actin is shown as a loading control.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Immunohistochemistry to detect LC3I, p62 and Atg5 in tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 18 weeks after AdCre inhalation. Note highly elevated levels of LC3I and p62, both indicative of defective autophagy, in KRas;Atg5fl/fl tumours. Scale bars, 50 μm. (d,e) Impaired formation of autophagosomes (arrows) in KRas;Atg5fl/fl tumour cells.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(d,e) Impaired formation of autophagosomes (arrows) in KRas;Atg5fl/fl tumour cells. (d) Representative electron microscopy images are shown for KRas;Atg5fl/+ and KRas;Atg5fl/fl tumours18 weeks after AdCre inhalation. Scale bars, 5 μm for upper and 2 μm for lower panels. M, mitochondria; *, lamellar bodies (Corpuscula lamellariae), rare cell organelles containing surfactant lipoproteins characteristic for type II pneumocytes. (e) Mean percentages (±s.e.m.) of tumour cells with detectable autophagosomes or autolysosomes, counted on electron microscopy images. n≥8 mice per genotype and at least 20 intact cells for each electron microscopy section were counted. ***P0.001 (χ2-test of a generalized linear model with logit link assessing the genotype effect).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Representative electron microscopy images of autolysosomes (left panels), autophagosomes (middle panels) and mitophagy (right panels), all indicated by arrows, in lungtumour cells from control KRas;Atg5fl/+ mice18 weeks after AdCre inhalation. Note the near-to-complete absence of such structures in the lungtumour cells from KRas;Atg5fl/fl littermates. Very rarely, we found cells with one autolysosome (left panels) or one single autophagosome (middle panels; arrows) in KRas;Atg5fl/fl tumours, whereas such structures can frequently be seen within single KRas;Atg5fl/+ tumour cells. Of note, the presence of a single autophagosome or a single autolysosome was scored as a positive event in Fig. 1e. Also note aberrant mitochondrial morphologies and increased mitochondrial numbers in KRas;Atg5fl/fl tumour cells. * indicates lamellar bodies. Scale bars, 2 μm. (b) Mean numbers (±s.e.m.) of mitochondria per lungtumour cell from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice18 weeks after tumour induction. Numbers of mitochondria were determined by electron microscopy. n≥8 mice per genotype and a minimum of 20 intact cells were counted per sample. ***P0.001 (χ2-test assessing the genotype effect in a generalized linear model with log link).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Mitochondria (arrows) in KRas;Atg5fl/+ and KRas;Atg5fl/fl lung tumour cells 18 weeks after AdCre inhalation. Note markedly altered mitochondrial morphology, that is, disorganized matrix structures, rounding and enlargement in the autophagy-defective KRas;Atg5fl/fl cells. Au, autophagosomes; Au-L, autolysosome; *, lamellar bodies. Scale bars, 2 μm.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(d-g) Bioenergetics profiling of purified tumour cells from KRas;Atg5fl/+ and KRas;Atg5fl/fl mice (e) 6 weeks and (g) 18 weeks after tumour induction. Representative experimental data are shown. Oxygen consumption rates (OCR) were used to detect the bioenergetics profiles of purified tumour cells using a Seahorse Bioscience 24XF extracellular flux analyser. OCR±s.e.m. were recorded to construct bioenergetics profiles for basal respiration (BR), ATP turnover (AT), respiratory capacity (RC), spare respiratory capacity (SRC) and proton leakage (PL). A minimum of seven different samples were analysed for each group. *P0.05; **P0.01(unpaired, two-sided t-test).",
    "ncbi_link": "Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Increased tumour initiation in KRas;Atg5fl/fl mice as compared with KRas;Atg5fl/+ littermates. Representative histological sections at 2 weeks after AdCre inhalation are shown. Insets show typical lung lesions. Haematoxylin and eosin staining. Scale bars, 2 mm for whole lung section; 50 μm for insets.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(b) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) in KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 2 weeks after AdCre inhalation. n=6 per group. **P0.01 (χ2-test assessing the genotype effect in a generalized linear model with log link).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Tumour growth curves based on mean tumour-to-lung area ratios (±s.e.m.) determined in KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates at the indicated time points. At least three different planes from each lung were analysed. n≥6 per cohort for each time point. *P0.05, **P0.01 (unpaired, two-sided Wicoxon test).",
    "ncbi_link": "Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(d) MicroCT analysis of lung tumours of KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice 18 weeks after AdCre inhalation. Representative data from individual mice are shown. Scale bars, 5 mm",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Distribution and (b) absolute numbers of hyperplastic lesions, adenomas and adenocarcinomas in KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice6, 12 and 18 weeks post AdCre infection. Data are shown as means±s.e.m.; n=6 per group. Combining the tumour progression data from 6, 12 and 18 weeks, a cumulative linked mixed model (clmm) analysis showed also a significant dependency of tumour progression on the genotype; P0.05 (χ2-test of clmms assessing the genotype effect). Applying generalized linear-mixed effects (glmer) models with logit link to individual time points, shows a significant dependency of the transition from hyperplastic lesions to adenomas (12 weeks, P0.05) and from adenomas to adenocarcinomas (12 weeks, P0.01 and 18 weeks, P0.01) on the mouse genotype (the last three P-values are from χ2-tests of a generalized linear models with logit link assessing the genotype effect).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c,d) Histological analyses (haematoxylin and eosin staining) of lung tumours in KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 18 weeks after AdCre inhalation. (c) Nuclear and cellular polymorphy, more dense and sometimes irregular chromatin as well as more nucleoli in tumour cells of KRas;Atg5fl/+ mice as compared with KRas;Atg5fl/fl tumours. Sections were analysed 18 weeks after AdCre inhalation. Scale bars, 50 μm. (d) KRas;Atg5fl/fl tumours exhibited markedly increased apoptotic figures and necrotic areas in the centre of larger tumours (asterisk).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c,d) Histological analyses (haematoxylin and eosin staining) of lungtumours in KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 18 weeks after AdCre inhalation. (c) Nuclear and cellular polymorphy, more dense and sometimes irregular chromatin as well as more nucleoli in tumour cells of KRas;Atg5fl/+ mice as compared with KRas;Atg5fl/fl tumours. Sections were analysed 18 weeks after AdCre inhalation. Scale bars, 50 μm. (d) KRas;Atg5fl/fl tumours exhibited markedly increased apoptotic figures and necrotic areas in the centre of larger tumours (asterisk).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Primary pneumocytes were infected with AdCre for 96 h and Atg5 protein expression determined by western blot. β-actin is shown as a loading control.",
    "ncbi_link": "AdCre: 
Atg5: 11793"
  },
  {
    "caption": "(b) Atg5 mRNA expression was determined by quantitative PCR. Data are shown as mean relative mRNA expression±s.e.m. in KRas;Atg5fl/fl tumours as compared with tumours from KRas;Atg5fl/+ mice (set to 1). Values were normalized to β-actin mRNA expression. n=3 per group.",
    "ncbi_link": "β-actin: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(b) Representative immunohistochemistry and quantitative assessment of γH2AX and phospho-Chk2 in lung tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 18 weeks after AdCre inhalation. For γH2AX and phospho-Chk2 staining, sections were scored independently in a double-blinded manner. Data are shown as mean percentages (±s.e.m.) of positive cells per total cell numbers. n=6 mice per genotype. Scale bars, 50 μm. ***P0.001 (χ2-test of a generalized linear model with logit link assessing the genotype effect).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Representative histological lung sections of KRas;Atg5fl/+;p53fl/fl and KRas;Atg5fl/fl;p53fl/fl littermate mice16 weeks after AdCre inhalation. Scale bars, 2 mm. (d) Distribution of hyperplastic lesions, adenomas and adenocarcinomas (±s.e.m.) in KRas;Atg5fl/+;p53fl/fl and KRas;Atg5fl/fl;p53fl/fl littermates 16 weeks post AdCre infection (n=4 per genotype).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653
p53: 22059"
  },
  {
    "caption": "(e) The Kaplan-Meier survival curves for KRas;Atg5fl/+;p53fl/fl (n=8) and KRas;Atg5fl/fl;p53fl/fl (n=9) littermate mice injected intranasally with AdCre (2.5 × 107 p.f.u.). There was no statistical difference between the cohorts (log-rank test).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653
p53: 22059"
  },
  {
    "caption": "(a,b) Representative immunohistochemistry and quantitative assessment of (a) tumour-infiltrating CD3ε-positive T cells and (b) FoxP3+ Tregs in lung tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 6 weeks after AdCre inhalation. Data are shown as mean percentages (±s.e.m.) of the indicated cell types per total cell numbers in the tumour areas. Only cells within tumours were scored. At least six mice per genotype were analysed. Scale bars, 50 μm. ***P0.001(χ2-test assessing the genotype effect in a generalized linear model with logit link).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Representative immunohistochemistry and quantitative assessment of FoxP3+ Tregs in lung tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 2 weeks after AdCre inhalation. Data are shown as mean percentages (±s.e.m.) of FoxP3+ cells among total cell numbers in the tumour areas. Only cells within tumours were scored. At least six mice per genotype were analysed. Scale bars, 50 μm. **P0.01(χ2-test assessing the genotype effect in a generalized linear model with logit link).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(d) FACS blots to detect CD25+FoxP3+ Treg cells in lungs 2 weeks after AdCre inhalation. Cells were gated on CD4+ populations. Numbers indicate percentages among total CD4+ cells in the lungs.",
    "ncbi_link": "AdCre: "
  },
  {
    "caption": "(e) Mediastinal lymph node and lung cells were isolated from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates 2 weeks after AdCre inhalation and stained for flow cytometric analysis as described in Methods. The left panel shows the percentage of CD4+ T cells among all lung-infiltrating CD45+ haematopoietic cells (±s.e.m.). The right panel shows the percentage of FoxP3+ cells among CD4+ T cells in mediastinal lymph nodes and lungs (±s.e.m.). n=4 per genotype; *P0.05 (unpaired, two-sided t-test).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) in KRas;Atg5fl/+ and KRas;Atg5fl/fl mice2 weeks after AdCre inhalation treated either with an isotype control Ab or a depleting anti-CD25 Ab. n=4 per group. **P0.01 (χ2-test assessing the genotype effect in a generalized linear model with log link). (b) Histological lung sections of KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice treated with an isotype control Ab or anti-CD25-immunodepleting Abs. Mice were killed 2 weeks after AdCre inhalation and their lungs were processed for histopathology. Representative lung images (haematoxylin and eosin (HE) staining) are shown for each genotype and treatment. Scale bars, 2 mm.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) in KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 2 weeks after AdCre inhalation treated either with an isotype control Ab or an Ab specific to FR4. n=4 per group. ***P0.001 (χ2-test assessing the genotype effect in a generalized linear model with log link). (d) Histological lung sections of KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice treated with isotype control Abs or Abs specific to FR4. Mice were killed 2 weeks after AdCre inhalation and their lungs were processed for histopathology. Representative lung images (HE staining) are shown for each genotype and treatment. Scale bars, 2 mm.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(b) Protein expression of Hif1α, Atg5 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in isolated KRas;Atg5fl/+ and KRas;Atg5fl/fl pneumocytes (analysed at 4 days after AdCre infection) and tumours purified from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermate mice at week 2 after AdCre inhalation. Quantifications of the hypoxia-inducible factor (HIF)1α/GAPDH ratios are shown for each lane; two independent blots are quantified.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) CD39, Atg5 and as a control β-actin protein expression in isolated Atg5fl/+, Atg5fl/fl, KRas;Atg5fl/+ and KRas;Atg5fl/fl pneumocytes. Protein lysated were analysed at 4 days after AdCre infections by western blot. Quantifications of the CD39/β-actin ratios are shown for each lane, normalized to the Atg5fl/+ samples. Two independent blots are quantified.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(d,e) CD39, Atg5 and as a control β-actin protein expression in isolated KRas;Atg5fl/+ and KRas;Atg5fl/fl pneumocytes treated with the (d) HIF1α inhibitor 3-(2-(4-adamantan-1-yl-phenoxy)-acetylamino)-4-hydroxybenzoic acid methyl ester or left untreated and (e) the Nrf2 inhibitor Brusatol (100 nM) or the ROS scavenger N-acetyl-L-cysteine (5 mM). Protein lysates were analysed on day 4 by western blot. Quantifications of the CD39/β-actin ratios are shown for each lane. The inhibitors were present during the entire 4 day culture period.",
    "ncbi_link": "Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(a) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) and (b) representative histological lung sections (haematoxylin and eosin (HE) staining) of KRas;Atg5fl/+ and KRas;Atg5fl/fl mice2 weeks after AdCre inhalation treated in vivo either with either vehicle control or POM1 (intraperitoneally; i.p. 10 mg kg−1 daily) to inhibit CD39 activity. n=4 per group. ***P0.001 (χ2-test assessing the genotype effect in a generalized linear model with log link). Scale bars, 2 mm.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(c) Quantification of numbers of hyperplastic lesions/per lung (mean values±s.e.m.) and (d) representative histological lung sections (HE staining) of KRas;Atg5fl/+ and KRas;Atg5fl/fl mice 2 weeks after AdCre inhalation treated either with either vehicle control or the adenosine receptor blocker PSB1115 (i.p. 10 mg kg−1 daily). n=4 per group. **P0.01 (χ2-test assessing the genotype effect in a generalized linear model with log link). Scale bars, 2 mm.",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "(e,f) Representative immunohistochemistry and quantitative assessment of FoxP3+ Tregs in lung tumours from KRas;Atg5fl/+ and KRas;Atg5fl/fl littermates treated with vehicle control or the CD39 blocker polyoxometalate-1 (POM1) and treated with vehicle or the adenosine receptor inhibitor PSB1115 (4-(2,3,6,7-tetrahydro-2,6-dioxo-1-propyl-1H-purin-8-yl)-benzenesulphonic acid potassium salt). Mice were killed 2 weeks after AdCre inhalation and their lungs were processed for immunohistopathology. Data are shown as mean percentages (±s.e.m.) of FoxP3+ cells among total cell numbers in the tumour areas. Only cells within tumours were scored. At least four mice per genotype were analysed. Scale bars, 50 μm. **P0.01. NS, not significant; (χ2-test assessing the genotype effect in a generalized linear model with logit link).",
    "ncbi_link": "AdCre: 
Atg5: 11793
KRas: 16653"
  },
  {
    "caption": "The ERMIT assay relies on the signaling properties of IRE1, one of the three ER stress sensors and reports for a dimerization event occurring in the lumen of the ER. The assay can be applied to heterodimerization or homodimerization events. Western blot showing the expression of AGR2 dimers (D) and monomers (M) in HEK293T subjected to DSP-mediated cross-linking and that were previously transfected with either a control siRNA (siCTL) or a siRNA targeting AGR2 (siAGR2) for 24 h (C) Reduced or non-reduced samples were resolved by SDS-PAGE and immunoblotted using anti-AGR2, anti-ERK1 antibodies (for loading control).",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "The ERMIT assay relies on the signaling properties of IRE1, one of the three ER stress sensors and reports for a dimerization event occurring in the lumen of the ER. The assay can be applied to heterodimerization or homodimerization events. G) Cells expressing various bait and prey constructs and the XBP1 splicing reporter or the XBP1 splicing reporter alone were exposed to increasing concentrations of DTT. The ERMIT signals obtained with both baits were then normalized to that of XBP1s to obtain results independent of the activation of endogenous IRE1 by the use of chemical ER stressors (n = 4).",
    "ncbi_link": "XBP1: 
IRE1: 2081"
  },
  {
    "caption": "C) Changes in AGR2 dimer and monomer ratio in TMED2 overexpressing cells. DSP-stabilized AGR2 was analyzed under non-reducing (top blot) or reducing conditions (bottom blot). D=dimeric, M=monomeric AGR2.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "E): Co-immunoprecipitation of AGR2 wild-type (WT, left panel) or AGR2 AA mutant (right panel) with TMED2 in HEK293T cells. Immunoprecipitation was performed with mouse anti-Flag antibody to pull-down the ectopic protein tag.",
    "ncbi_link": "AGR2: 10551
TMED2: 10959"
  },
  {
    "caption": "F) Western blot analysis (left panel) and quantification (right panel) of AGR2 intracellular expression upon TMED2 overexpression. Data are representative of 4 independent experiments. Tubulin (TUB) was used as a loading control.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "G) HEK293T cells were transfected with control (ev) or TMED2 plasmid and then used in the ERMIT assay with AGR2 WT (n=3).",
    "ncbi_link": "AGR2: 10551
TMED2: 10959"
  },
  {
    "caption": "H) Western blot analysis (left panel) and quantification (right panel) of AGR2 intracellular expression in total cell lysate (TCL) upon TMED2 silencing. Data are representative of 4 independent experiments. Tubulin (TUB) was used as a loading control.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "I) HEK293T cells were silencing for TMED2 and then used in the ERMIT assay with AGR2 WT (n=3).",
    "ncbi_link": "AGR2: 10551
TMED2: 10959"
  },
  {
    "caption": "B-C) Expression and subcellular localization of CD59-GFP WT and C94S.",
    "ncbi_link": "GFP: 
CD59: 966"
  },
  {
    "caption": "F-I) FACS analysis of CD59 WT (F and G) or CD59 C94S (H and I) total (F and H) and membrane (G and I) expression in HEK293T cells silenced for AGR2 (siAGR2) and TMED2 (siTMED2) when compared to control (siGL2) cells (F and H) or silenced for TMED2 (siTMED2) and overexpressing AGR2 WT or AGR2 AA mutant (G and I). Data are representative of three to four independent experiments. Membranous CD59 expression was detected with anti-GFP APC. ns: non-statistically significant; for F (*): p=0.0385, (***): p=0.0003 (left panel) and p=0.0002 (right panel), respectively; for G (*): p=0.0334, (**) p=0.0036 and (***) p=0.0003; for H (*): p=0.0171 and (**): p=0.0084; and for I (**) p=0.0086 (left panel) and p=0.0076 (right panel), respectively.",
    "ncbi_link": "GL2: 
AGR2: 10551
CD59: 966
TMED2: 10959"
  },
  {
    "caption": "A) Formation of GFP-LC3 autophagic puncta in TMED2 overexpressing HEK239T cells as monitored using confocal microscopy (right panel). DAPI was used for nuclear staining visualization. Percentage of GFP-LC3 puncta in control (CTL) and TMED2 overexpressing HEK293T cells as quantified from three independent experiments by counting 240 GFP-LC3 positive cells for each condition (left panel). (**): p=0.0032.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "B) Western blot detection (left panel) and quantification (right panel) of LC3 level in control and TMED2 overexpressing HEK293T cells treated or not with 50 µM chloroquine for 2 hours. Actin (ACT) served as a loading control. (*): p=0.0498.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "C) Western blot analysis of AGR2 expression in control and TMED2 overexpressing HEK293T cells upon autophagy inhibition with 20 µM and 10 µM chloroquine treatment. Actin (ACT) served as a loading control.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "D) HEK293T cells were transfected with control (ev) or TMED2 plasmid and then used in the ERMIT assay with AGR2 WT the presence of gradual amounts of chloroquine.",
    "ncbi_link": "AGR2: 10551
TMED2: 10959"
  },
  {
    "caption": "E) Western blot analysis of secreted AGR2 upon TMED2 overexpression. eAGR2, extracellular AGR2; iAGE2, intracellular AGR2.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "F) Representative pictures of extracellular vesicles (EVs) heterogeneity purified from conditioned media of HEK293T cells transfected with control (ev) or TMED2 plasmid and analyzed by cryo-electron microscopy. Right upper panel: western blot analysis of CD63 in total medium (left) and in the purified extracellular vesicles fraction purified from media conditioned by control and TMED2 overexpressing cells (middle) and western blot analysis of AGR2 levels (right) in extracellular vesicles enriched from culture media conditioned by control and TMED2 overexpressing cells.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "G) Western blot analysis of secreted AGR2 upon TMED2 silencing eAGR2, extracellular AGR2; iAGE2, intracellular AGR2. H) Quantification of extracellular AGR2 level (eAGR2) in cells silenced for TMED2 (siTMED2), compared to control (siGL2). Data are representative of three independent experiments and are presented as extracellular-to-intracellular AGR2 ratio. (**): p=0.0029.",
    "ncbi_link": "GL2: 
TMED2: 10959"
  },
  {
    "caption": "I) Secretion of AGR2 wild-type (wt), E60A and ∆45 mutant as determined by Western blot. eAGR2, extracellular AGR2; iAGE2, intracellular AGR2.",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "A) Representative histological H&E staining of sections of the proximal colon and ileum of WT and TMED2 hypomorph mice.",
    "ncbi_link": "TMED2: 56334"
  },
  {
    "caption": "B) Immunohistological analysis of AGR2 and MUC2 expression in the proximal colon of WT and TMED2 hypomorph mice.",
    "ncbi_link": "TMED2: 56334"
  },
  {
    "caption": "C) Semi-quantitative analysis of AGR2 and MUC2 expression in the proximal colon of WT (blank bars) and TMED2 hypomorph mice (black bars) (n=6).",
    "ncbi_link": "TMED2: 56334"
  },
  {
    "caption": "D) Freshly isolated PBMCs were placed in Boyden chambers towards media conditioned by cells overexpressing AGR2 WT, E60A, ∆45 or AGR2 AA mutants and incubated for 24 h. Migrating cells were then characterized and quantified by flow cytometry using FCS/SSC parameters or CD14 monocyte marker. (**): p=0.0016.",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "E and F) Freshly isolated PBMC were placed in Boyden chambers towards media conditioned by cells overexpressing TMED2 and either AGR2 WT (E) or AGR2 AA mutant (F) and incubated for 24 h. Migrating cells were then characterized and quantified For E (*): p=0.0461 (AGR2WT/TMED2) and 0.018 (AGR2WT/TMED2 + blocking Ab) respectively; (**): p=0.0053 and (***): p=0.0048; for F (***): p=0.0007.",
    "ncbi_link": "AGR2: 10551
TMED2: 10959"
  },
  {
    "caption": "G) Freshly isolated PBMC were placed in Boyden chambers towards media conditioned by cells silenced for TMED2 and incubated for 24 h. Migrating cells were then characterized and quantified (*): p=0.0149.",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "H) Freshly isolated PBMC were placed in Boyden chambers towards decreased doses of recombinant AGR2 and incubated for 24 h. CCL2 cytokine was used as positive control for monocyte migration. ns: non-statistically significant, (*): p=0.0171, (**): p=0.0084, (***): p=0.0003.",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "A) Selective enrichment of AGR2 modulators in colonic Crohn's disease (CD). Percentage of tested genes with altered expression in colonic biopsies from patients with Ulcerative Colitis (UC, n=8) and colonic CD (CC, n=15) and in ileal biopsies from patients with ileo-colonic CD (IC, n=9).",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "B) Hierarchical clustering of the AGR2 modulator genes significantly deregulated in non-inflamed colonic mucosa from patients with Crohn's Disease (CD) versus healthy controls (C) (dChip software t-Test)",
    "ncbi_link": "AGR2: 10551"
  },
  {
    "caption": "C) TMED2 mRNA expression in healthy controls (CT), colonic Crohn's disease (CC) and ulcerative colitis (UC).",
    "ncbi_link": "TMED2: 10959"
  },
  {
    "caption": "D. U2OS cells were transfected with control (siLuc) or MRE11 targeting siRNA (siMRE11). After 48 hours cells were either mock or pretreated with 10 μM XL413 and labelled with CldU (red) for 30 minutes. Where indicated 50 nM CPT was added and then cells were labelled with IdU (green). A set of representative DNA fibres from each condition is shown and the IdU/CIdU tract length ratio is plotted. The box extends from the 25th to the 75th percentile with the line in the box representing the median. Whiskers indicate the 10-90 percentileswith data outside this range for individual outliers being plotted as dots. At least 100 replication forks were analyzed for each condition. P values were calculated using one way ANOVA Kruskal-Wallis test and Dunn's multiple comparison post test (ns, not significant, **** p<0.0001) and are related to the experiment shown. Similar results were obtained in a second independent experiment.",
    "ncbi_link": "MRE11: 4361"
  },
  {
    "caption": "F. Frequency of reversed replication forks isolated from mock-depleted (siLuc) and BRCA2-depleted (siBRCA2) U2OS cells upon 5 hour treatment with 4 mM HU in the presence and absence of 10 μM XL413. The number of replication intermediates analyzed is indicated in parentheses. Similar results were obtained in two independent experiments (Appendix Table",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "G. Amount of ssDNA length at the junction (Red arrows in Figure 4D) in siLuc and siBRCA2 U2OS cells treated with 4 mM of HU for 5 hours in the presence or absence of XL413. N indicates the number of forks observed, and only molecules with detectable ssDNA stretches are included in the analysis. The lines show the mean length of ssDNA regions at the fork and the value is displayed above the plot",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "A. Representative metaphase spread from BRCA2 depleted U2OS cell treated with HU. Scale bar = 5 μM. Arrows indicate the chromosomes enlarged in the insets, two of which show chromatid breaks (*",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "D-E. U2OS and AS-CDC7 cells were transfected with control (siCon) or BRCA2 (siBRCA2) targeting siRNAs. 48 hours post transfection cells were either mock-treated or treated with 10 μM XL413 or 10 μM 3MB-PP1 respectively for 24 hours with Nocodazole added for the last 16 hours of the experiment. The graph shows the average number of chromatid breaks per spread. In each experiment 30 chromosome spreads for each condition were analysed and three independent experiments were performed. Error bars represent SEM. Statistical significance assessed by student t test (*p<0.05, *** p<0.001",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "b. Heatmap depicting mean  expression of the top 20 upregulated genes of fibroblast  isolated from wound-induced tumours (Pap) compared to fibroblasts from wild-type (WT) and inflamed (InvEE)   back  skin (n=3 per condition).  PRSS35 is indicated in red as a top upregulated gene in  CAFs.",
    "ncbi_link": "PRSS35: 244954"
  },
  {
    "caption": "a.  Immunofluorescent images  of skin sections from  PDGFRα-eGFP reporter mice with normal (WT, n=4), inflamed (InvEE, n=4), wounded (d14 post-wounding;  wound, n=4), or tumour-associated (Papilloma, Pap d17 and d30 post-wounding, n=4 per condition) skin. Nuclei  were  stained  with Dapi  (4', 6-diamidino- 2- phenylindole; blue). Dotted line represents  epidermal-dermal   boundary. Scale bars: 50 μm. b. Quantification of the  number of fibroblasts present in different skin conditions (n=4 mice per condition; ** p<0.01; *** p<0.001; **** p<0.0001; One-way ANOVA testing). Data represent means of multiple microscopic fields ± S.E.M. ",
    "ncbi_link": "eGFP: 
PDGFRα: 18595"
  },
  {
    "caption": "c. Relative mRNA levels of PRSS35 in lysates from normal skin (WT, n=4  mice), inflamed skin (InvEE, n=4 mice), wounds  (d14pw, n=4 mice) and wound-induced  papillomas (Pap, n=5  mice). (* p=0.0159; Mann-Whitney test). Data represent means of three technical replicates ± S.E.M.",
    "ncbi_link": "PRSS35: 244954"
  },
  {
    "caption": "f. H&E-stained skin sections of WT and PRSS35-/- wounds at different days post-wounding. Scale bars: 100 µm.",
    "ncbi_link": "PRSS35: 244954"
  },
  {
    "caption": "c, d. Incidence of  papilloma  formation (ns: non-significant; Gehan-Breslow-Wilcoxon test) (c) and number of tumours per mouse (d) in wild-type (WT, n=17) and PRSS35-/- (n=22) mice treated with DMBA-TPA (*p=0.0171; Wilcoxon matched-paired rank test). Data represent means ± S.E.M.",
    "ncbi_link": "PRSS35: 244954"
  },
  {
    "caption": "b. Relative mRNA expression levels of the indicated  ECM genes in primary  fibroblast  cultures (col1a1: collagen type 1 alpha 1; αSMA, alpha smooth muscle actin;  Cyr61: Cysteine-rich angiogenic inducer 61 (=CCN1)) in primary fibroblast  cultures isolated from WT and PRSS35-/- mice, untreated or after 24 hours stimulation with 10 ng/mL TGFβ1  (n≥7 biological replicates per condition) (** p<0.01, *** p<0.001, **** p<0.0001.; Two-way ANOVA with multiple comparisons). Data represent means ± S.E.M. c Relative  mRNA expression levels of the indicated cytokines/growth factors in primary fibroblast  cultures (n≥8 per condition) (VEGF-α, vascular endothelial growth factor-alpha; FGF2: basic fibroblast growth factor;  FGF7: keratinocyte growth factor) (* p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.; Two-way ANOVA with multiple comparisons). Data represent means ± S.E.M. ",
    "ncbi_link": "alpha smooth muscle actin: 11475
αSMA: 11475
Cyr61: 16007
Cysteine-rich angiogenic inducer 61: 16007
col1a1: 12842
collagen type 1 alpha 1: 12842
basic fibroblast growth factor: 14173
FGF2: 14173
FGF7: 14178
keratinocyte growth factor: 14178
PRSS35: 244954
vascular endothelial growth factor-alpha: 22339
VEGF-α: 22339"
  },
  {
    "caption": "d.  Picrosirius red staining of normal  skin, day 14 post-wounding (d14pw) skin or wound-induced papillomas from WT and PRSS35 KO mice. Red colouring indicates thick  fibres, green colouring indicates thin fibres. Scale bars: 200 µm. e. Quantification of picrosirius red staining as total collagen  density (upper panel) and ratio of red versus green picrosirius staining (lower panel). Using QuPath Bioimage analysis software pixels colouring red or green were determined per area. (n≥4 technical replicates per condition) (* p<0.05, ** p<0.01, **** p<0.0001.; Two-way ANOVA with multiple comparisons). Data represent means ± S.E.M. ",
    "ncbi_link": "PRSS35: 244954"
  },
  {
    "caption": "(d) Two distinct siRNAs against NLRP3 and an irrelevant control siRNA were utilized to knock down RNA levels by lipofectamine transfection in macrophages that were later incubated with iRBCL, or RBCL as control, with or without XO, before quantification of secreted IL1β. Results are representative of 2 independent experiments with different donors.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "Schematic, western blot, and immunofluorescence  analysis of the 3×FLAG-UBXD8  knockin U2OS  cell line. Scale bar, 5 μm. Data information: In C, mitochondria  were visualized by anti-Tom20 immunostaining; ER  was labeled by anti-PDI immunostaining.",
    "ncbi_link": "FLAG: 
UBXD8: 23197"
  },
  {
    "caption": "Blue native gel analysis of UBXD8  in mitochondrial  fractions purified from WT and ∆UBXD8 HeLa  cells.",
    "ncbi_link": "UBXD8: 23197"
  },
  {
    "caption": "Immunoprecipitation  analysis of UBXD8 interaction  with mitochondrial  (MARCH5  and MUL1) and ER  (RNF185) ubiquitin E3  ligases. HeLa  cells were infected with lentivirus  to stably express HA-tagged ubiquitin E3  ligases. Whole cell lysates were prepared for anti-HA immunoprecipitation.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "Immunoprecipitation  analysis of UBXD8 interaction  with MARCH5  and RNF185. Whole cell lysates from 3×FLAG-UBXD8  knockin HEK293T  cells were prepared for anti-FLAG immunoprecipitation. MARCH5  and RNF185: short exposure for whole cell lysate blots, long exposure for FLAG-IP blots.",
    "ncbi_link": "FLAG: 
UBXD8: 23197"
  },
  {
    "caption": "Fractionation analysis of UBXD8's effect on VCP  recruitment to mitochondria  and the ER. Whole cell lysate, mitochondria, and ER  fractions were purified from WT, ∆UBXD8, and ∆UBXD8 HeLa  cells rescued with UBXD8  or the UBX* mutant. UBX*-UBXD8 carries four point mutations (K367A, F407A, P408G, R409A) in the UBX domain to disrupt the UBXD8-VCP interaction. For each sample, 5 μg proteins were loaded for  western blot  analysis.",
    "ncbi_link": "UBXD8: 23197"
  },
  {
    "caption": "A, B. Western blot (A) and quantitative (B) analyses of MiD49  and Mcl1  degradation in WT and ∆MARCH5 HeLa  cells. Cycloheximide  (CHX: 200 μg/ml; protein synthesis inhibitor); MG132: 20 μM, proteasome  inhibitor. Data information: Data are shown as mean ± SE from three biological repeats (B, Statistics: two-tailed unpaired Student's t-test (B, ; *P < 0.05, **P < 0.01, ***P < 0.001, n.s., not significant.",
    "ncbi_link": "MARCH5: 54708"
  },
  {
    "caption": "Fractionation analysis of the subcellular localization  of mito-UBXD8  and ER-UBXD8. Whole cell lysate, mitochondria, and ER  fractions were purified from the indicated HeLa  cells. Exogenously-expressed mito-UBXD8   has similar expression  level with endogenous UBXD8  in WT cells; exogenously-expressed WT UBXD8  and ER-UBXD8  have similar expression  levels.",
    "ncbi_link": "UBXD8: 23197"
  },
  {
    "caption": "D, E. Western blot (D) and quantitative (E) analyses of Mcl1  degradation in the indicated HeLa  cells. ∆UBXD8 HeLa  cells were rescued with vector, WT-, mito-, and ER-UBXD8. Data are shown as mean ± SE from three biological repeats (E). Statistics: two-tailed unpaired Student's t-test (E); *P < 0.05, **P < 0.01, ***P < 0.001.",
    "ncbi_link": "UBXD8: 23197"
  },
  {
    "caption": "Western blot analysis of BH3-domain containing proteins in the indicated HeLa  cells treated with Doxo  (10 μM). Three proteins with enhanced level in ∆UBXD8 cells (Noxa, Bik, and Bnip3) are highlighted in red.",
    "ncbi_link": "UBXD8: 23197"
  },
  {
    "caption": "C. Localization of GFP fused with wild-type or mutant MLS of GASZ in HeLa cells. Mitochondrial localization was monitored by MitoTracker (Red) staining. Scale bars: 15 m.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "G. Co-IP assays of GFP-GASZ with various FLAG-tagged wild-type GASZ or its deletion mutants in 293T cells",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "A. Mitochondria visualized by MitoTracker (Red) when wild-type GASZ or GASZ with MLS mutation was expressed in HeLa cells. Scale bar: 15 m.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "B. EM on 293T cells with empty vector control (Ctrl), wild-type GASZ, or GASZ with F to P mutation in MLS. Scale bar: 1 m. N: nucleus.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "C. Averaged percentage of HeLa cells (determined from 100 cells in each experiment) with different types of mitochondria determined by MitoTracker (Red) staining when transfected with GASZ, its SAM/ZIP deletion mutant, or GASZ with MLS mutation.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "D. HeLa cells transfected with COX4-DsRed, mito-PAGFP, and empty vector control, GASZ or GASZ with MLS mutation, followed by photoactivation of PAGFP. Representative images of PAGFP and DsRed were taken at 0, 10, and 20 min post photoactivation. Scale Bar: 10 m. Insets show images with higher magnification. The averaged exponential decay constant (±s.e.m.) of normalized PAGFP fluorescence within the designated region (white circle) at photoactivation area over a period of 10 min was shown as a bar graph below. n>20 cells for each group.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "E. Averaged percentage of C18-4 cells (determined from 100 cells in experiment) with different types of mitochondria determined by MitoTracker (Red) staining when transfected with Su9-GFP or GFP-GASZ.",
    "ncbi_link": "GASZ: 74068
Su9: 66152"
  },
  {
    "caption": "F. Real-time PCR analyses of mtDNA copy numbers on testes at different time points postnatal, relative to a single copy gene, PECAM, encoded by nuclear DNA. n=5 per genotype.",
    "ncbi_link": "PECAM: "
  },
  {
    "caption": "C. Co-IP assays of HA-tagged MFN1 with various FLAG-tagged wild-type GASZ, its domain deletion mutants, or GASZ with MLS mutations in 293T cells.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "D. Averaged percentage of MEFs with different types of mitochondria were determined according to the mitochondrial morphology by MitoTracker (Red) staining in wild-type MEFs, or MEFs containing MFN null mutations transfected with empty vector control (Ctrl) or a GASZ expressing plasmid.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "E. PEG fusion assays of Su9-GFP and COX4-DsRed labeled wild-type MEFs, or MEFs containing MFN null mutations transfected with empty vector control (Ctrl) or a GASZ expressing plasmid. Bar graph represents averaged percentage of areas with different levels of mitochondrial fusion.",
    "ncbi_link": "GASZ: 74068"
  },
  {
    "caption": "A. Gross morphology of testes from MFN1f/f-Cre compared to their wild-type littermates.",
    "ncbi_link": "Cre: 
MFN1: 67414"
  },
  {
    "caption": "B. Histological studies of testis sections from wild-type mice or MFN1f/f-Cre littermates at different time points postnatal. Red stars: tubules with spermatocytes.",
    "ncbi_link": "Cre: 
MFN1: 67414"
  },
  {
    "caption": "D. EM of testical sections from wild-type neonatal mice or MFN1f/f-Cre littermates. N: nucleus.",
    "ncbi_link": "Cre: 
MFN1: 67414"
  },
  {
    "caption": "B. Whole exome sequencing was carried out and analysis revealed a missense p.L165F variant (c.493 C>T) in the ALX1 homeodomain, heterozygous in the parents (ALX1165L/165F), wildtype in the unaffected sibling (ALX1165L/165L), and homozygous in both affected subjects (ALX1165F/165F).",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "F. Expression of pluripotent (OCT4, NANOG), endoderm (Endo., AFP, GATA4, FOXA2), ectoderm (Ecto., NESTIN, GFAP, SOX1), and mesoderm (Meso., BRACH. (BRACHYURY), RUNX1, CD34) gene markers for ALX1165L/165L (green), ALX1165L/165F(red), and ALX1165F/165F (blue) iPSC relative to undifferentiated cells (UND). Data are represented as pooled mean ± SEM of three experiments on three clones from each genotype. Significance: p=0.0167 for OCT4, p=0.0005 for NANOG, p= 0.000004 for AFP, p=0.0082 for GATA4, p=0.0137 for FOXA2, p=0.00002 for NESTIN, p=0.0167 for GFAP, p=0.0014 for SOX1, p=0.0117 for BRACHYURY, p=0.0008 for RUNX1 and p=0.0068 for CD34 when comparing undifferentiated and differentiated ALX1165L/165L iPSC. p=0.0013 for OCT4, p=0.0011 for NANOG, p=0.0000003 for AFP, p=0.0003 for GATA4, p=0.0063 for FOXA2, p=0.0001 for NESTIN, p=0.027 for GFAP, p =0.000002 for SOX1, p=0.000009 for BRACHYURY, p=3e-9 for RUNX1 and p=0.000006 for CD34 when comparing undifferentiated and differentiated ALX1165F/165L iPSC. p=0.0201 for OCT4, p=0.006 for NANOG, p=1x10-12 for AFP, p=5x10-13 for GATA4, p=0.0031 for FOXA2, p=0.0292 for NESTIN, p=0.00001 for GFAP, p=6x10-7 for SOX1, p=0.0204 for BRACHYURY, p=0.0009 for RUNX1 and p=0.000003 for CD34 when comparing undifferentiated and differentiated ALX1165F/165F iPSC. Data from each clone were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant.",
    "ncbi_link": "AFP: 174
ALX1: 8092
CD34: 947
FOXA2: 3170
GATA4: 2626
GFAP: 2670
NANOG: 79923
NESTIN: 10763
OCT4: 5460
RUNX1: 861
SOX1: 6656
BRACH: 6862
BRACHYURY: 6862"
  },
  {
    "caption": "Gene expression analysis across NCC differentiation of unaffected control ALX1165L/165L (green), heterozygous ALX1165L/165F (magenta) and homozygous ALX1165F/165F iPSC: ALX1, neural plate border specifier genes ZIC1, PAX7, PAX3, MSX1, MSX2, DLX5; neural crest specifier genes FOXD3, P75, TFAP2A, SNAI2, TWIST1; and lineage specifier gene HAND2. The RT-qPCR relative expression values were normalized to RPLP0 and GAPDH expression. Data is represented as pooled mean ± SEM of three experiments on three clones from each genotype. Exact p-values are provided in Table EV1. Data from each clone were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant.",
    "ncbi_link": "GAPDH: 
RPLP0: 
ALX1: 8092
DLX5: 1749
FOXD3: 27022
HAND2: 9464
MSX1: 4487
MSX2: 4488
P75: 4804
PAX3: 5077
PAX7: 5081
SNAI2: 6591
TFAP2A: 7020
TWIST1: 7291
ZIC1: 7545"
  },
  {
    "caption": "A. Homozygous ALX1165F/165F NCC (blue) showed an increase in sensitivity to apoptosis when compared to control ALX1165L/165L NCC (black). The data on the left represents the mean percentage of Annexin V positive cells, indicative of apoptosis, as determined by FACS analysis, with the data on the right being an example of one such experiment. Apoptosis was induced by immersion in a 55°C water bath for ten minutes. Representative experiment for each condition is shown. Data is represented as pooled mean ± SEM of three independent experiments. Data obtained of each clone from three independent experiments were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant. . *: Significantly different from the basal apoptosis rate: p=3x10-12 between control NCC basal apoptosis and induced apoptosis, and between ALX1165F/165F NCC basal apoptosis and induced apoptosis. **: Significantly different from control NCC (p=0.0004). ",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "B. Expression levels of cyclins CCNA2 (blue) and CCND1 (orange) in NCC at passages 2 and 3 of ALX1165L/165L and ALX1165F/165F NCC. The RT-qPCR relative expression values were normalized to RPLP0 and GAPDH expression. Data is represented as pooled mean ± SEM of three experiments on three clones from each genotype. *: Significantly different from control NCC at passage 2 (p=0.001 between control and ALX1165F/165F NCC at passage 2 for CCNA2, p=0.0052 for CCND1). **: Significantly different from control NCC at passage 3 (p=0.0494 between control and ALX1165F/165F NCC for CCNA2, p=0.0008 for CCND1).",
    "ncbi_link": "GAPDH: 
RPLP0: 
ALX1: 8092
CCNA2: 890
CCND1: 595"
  },
  {
    "caption": "C. Fluorescence Activated Cell Sorting (FACS) experiments showed that control ALX1165L/165L NCC (green) exhibited increased expression of mesenchymal markers CD90, CD105, and CD73 with culture time (passages 1 through 4), whereas homozygous ALX1165F/165F NCC (blue) showed a consistent expression of the markers expressed at passage 1 throughout. Further, control ALX1165L/165L NCC showed a downregulation of CD57 expression with culture time, while ALX1165F/165F NCC maintained the same level of CD57 across passages. Data are presented as the mean percentage of positive-stained cells across passage numbers. Data obtained of each clone from three independent experiments were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant. *: Significantly different from control NCC. For CD90, p=0.0013 at passage 3 and p=0.0207 at passage 4. For CD105, p=0.0016 at passage 2, p=0.00004 at passage 3 and p=0.0021 at passage 4. For CD73, p=0.0060 at passage 2, p=0.00004 at passage 3 and p=0.0114 at passage 4. For CD57, p=0.0026 at passage 2, p=0.000003 at passage 3 and p=0.000007 at passage 4.",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "A. Mutant ALX1165F/165F NCC (blue) exhibited a migration defect in timed coverage of the central clearing of the wound assay when compared with control ALX1165L/165L NCC (black). Data is presented as percent area recovery of the central circular clear area of the wound assay by migrating NCC at the end of a 24-hour period. For fluorescent pictures, cells were stained in serum free media containing 3.6µM CellTracker Green CMFDA (Life Technologies) for 30 min at 37°C and allowed to recover for 30 min before starting the experiment. Images were acquired every 6 hours using a Keyence BZ-X800 microscope. Surface area analyses and percentages of coverage were measured using ImageJ software (NIH). The NCC were monitored over 24 hours. The data are represented as the average of the percentage of closure ± SEM. Scale bar = 200µm. Data obtained of each clone from three independent experiments were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant.*: Significantly different from control NCC (p<0.0001).",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "B. Multiplex analysis of BMP2 and BMP9 in the supernatant of cultured NCC showed that ALX1165F/165F NCC (blue) secrete less BMP2 and more BMP9 compared to control ALX1165L/165L NCC (green). Data are represented as pooled mean ± SEM of three clones from each genotype. Statistical significance was determined with an ANOVA test. A p-value <0.05 was considered significant. *: Significantly different from control NCC (p =0.0424 for BMP2 and p=0.0192 for BMP9).",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "C. Addition of soluble BMP2 or CV2, a BMP9 antagonist, to the culture medium could partially rescue the migration defect of ALX1165F/165F NCC. At the beginning of the assay, 10, 50, or 100 ng/ml of soluble BMP2, CV2, or a combination of the two at 100 ng/ml each were added to the culture medium, and the cells were monitored over the next 24 hours. The data are represented as the average of the percentage of closure ± SEM. Scale bar: 400µm.",
    "ncbi_link": "ALX1: 8092"
  },
  {
    "caption": "A. Dissected flatmount wild type and alx1-/- zebrafish larvae craniofacial cartilages after Alcian blue staining, the anterior points to the left of the page in all images. The ventral cartilages appear normal, but the alx1-/- anterior neurocranium (ANC) appears narrow, with the midline element that is derived from the frontonasal NCC being absent. The Meckel's cartilage (arrow, MC) is also diminutive. Scale bar: 200 µm.",
    "ncbi_link": "alx1: 565176"
  },
  {
    "caption": "B. Zebrafish alx1 mutants (blue) show reduced detectable expression of alx1 but increased expression of alx3, alx4a compared to wild type controls (green). alx4b expression levels are similar between wild type and alx1-/- lines. Data is represented as the mean of all pooled embryos from three different clutches. The RT-qPCR relative expression values were normalized to elfa and 18S expression using the ΔΔCT method. Data from each clutch were pooled and the mathematical mean was calculated. SEM was used to determine the standard error. To test statistical significance, an ANOVA test was performed. A p-value <0.05 was considered to be statistically significant. Statistical significance denoted by *; p<0.0001 between WT zebrafish and alx1-/- at all measured time points; at 10 ss, 24 hpf and 36 hpf for alx3; and at 24 hpf and 36 hpf for alx4a. Refer to Table EV2 for p-values.",
    "ncbi_link": "18S: 
elfa: 
alx1: 565176
alx3: 566955
alx4a: 100006399
alx4b: 497424"
  },
  {
    "caption": "C. Dissected flatmount of zebrafish embryos injected with Alx1DN, after Alcian blue staining. The embryos developed an absence of the frontonasal derived median portion of the anterior neurocranium (ANC) and a profound hypoplasia of the Meckel's and ventral cartilages. In the most severely affected zebrafish, a nearly abrogated ANC was observed. Scale bar: 200 µm.",
    "ncbi_link": "Alx1: 565176"
  },
  {
    "caption": "D. Lineage tracing experiments in control and Alx1DN mutant embryos revealed aberrant migration of anterior cranial NCC when alx1 is disrupted. In the control animal, the anterior cranial NCC always migrate to contribute to the median portion of the ANC. In contrast, the anterior cranial NCC labeled in the Alx1DN animals fail to migrate to the median ANC, where the ANC structure is narrower and the labeled cranial NCC are found in an anterior and lateral ectopic location (white asterisks). Scale bar: 250µm.",
    "ncbi_link": "alx1: 565176
Alx1: 565176"
  },
  {
    "caption": " (B) Bar diagram representation of the relative SUMO conjugation activity of Nse2, full-length Smc5-Nse2, ΔHinge/Smc5-Nse2, ΔHead/Smc5-Nse2 and Arm/Smc5-Nse2 truncation constructs (schematic representation above). Orange bars indicate the presence of ssDNA (virion ϕx174) and red bars absence of ssDNA. Reaction rates were performed at least in three different independent experiments (see Fig EV2). Data values are mean ± s.e.m.; and n=3 technical replicates. Significance was measured by a two-tailed unpaired t-test relative to wild-type. **P<0.01 ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (C) SYPRO-stained (left) and Western blot (right) time course SUMO conjugation reaction using and ΔHead/Smc5-Nse2 truncation construct in the presence of ssDNA. T7-tagged Smc5 and E1 were immunodetected by an anti-T7 antibody. Reactions were run at 30 °C and stopped at indicated times by adding SDS-loading buffer ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (D) SYPRO-stained (left) and Western blot (right) time course SUMO conjugation reaction using and ΔHinge/Smc5-Nse2 truncation construct in the presence of ssDNA. T7-tagged Smc5 and E1 were immunodetected by an anti-T7 antibody. Reactions were run at 30 °C and stopped at indicated times by adding SDS-loading buffer ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (E) Western blot of the time-course SUMO conjugation reaction in the presence of ssDNA (virion ϕx174) using either Nse2 (left) or Arm/Smc5-Nse2 complex (right). The reactions were run in the presence or absence of cNse4 external substrate. Reaction was run at 30°C and stopped at indicated minutes by adding SDS-loading buffer (N-S2, cNse4-SUMO2; N-2S2, cNse4-2SUMO2; N-3S2, cNse4-3SUMO2 and pS2, poly-SUMO2) ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (D) Bar diagram representation of the SUMO conjugation rates of activity assays of Arm/Smc5-Nse2 KE mutants in the presence (orange bars) or absence (red bars) of ssDNA (virion ϕx174), relative to wild-type (set to 1). Reactions rates were performed at least in three different independent experiments. Data values are mean ± s.e.m. and n=3 technical replicates. Significance was measured by a two-tailed unpaired t-test relative to wild-type. *P<0.05, **P<0.01, ***P<0.001 ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (C) Degree of conformational changes in CM induced by 60b linear ssDNA. Blue bar, Arm/Smc5-Nse2 (wild-type); grey bar, Arm/Smc5-Nse2 (K333E/K344E); green bar, Arm/Smc5-Nse2 (K764E); pink bar, Arm/Smc5-Nse2 (K333E/K344E/K764E); red bar, Arm/Smc5-Nse2 (K743E/K745E). Reactions were performed at least in three different independent experiments. Data values are mean ± s.d. and n=3 technical replicates. Significance was measured by a two-tailed unpaired t-test relative to wild-type. ****P < 0.0001 ",
    "ncbi_link": "Nse2: 856695
Smc5: 854123"
  },
  {
    "caption": " (B) Growth test analysis of wild-type, nse2-CH and the indicated smc5-KE mutants; 10-fold serial dilutions of the liquid cultures were spotted in YPD and pictures taken after 48 hours ",
    "ncbi_link": "nse2: 856695
smc5: 854123"
  },
  {
    "caption": " (C) Same as in (B) but using the nse2-CH, smc5-3KE, smc5-K743,745E, smc5-K743,745R, smc5-7KE and smc5-7KR mutants ",
    "ncbi_link": "nse2: 856695
smc5: 854123"
  },
  {
    "caption": " (A) Protein extracts from exponentially growing wild-type, smc5-3KE, smc5-K743,745E, smc5-4KE and smc5-K743,745R cells were prepared under denaturing conditions; 6xHis-Flag tagged SUMO (HF-SUMO) was pulled down from protein extracts to purify sumoylated species and analyzed by western blot. A strain with no HF-tag was used as control; arrow points to unmodified form of the protein, vertical bar to sumoylated forms ",
    "ncbi_link": "smc5: 854123"
  },
  {
    "caption": " (B) Left, same as in (A), but using wild-type and two independent clones of smc5-7KE; right, same as in (A), but using wild-type, smc5-7KE and smc5-7KR mutant cells ",
    "ncbi_link": "smc5: 854123"
  },
  {
    "caption": " (C) Quantification of Smc5 sumoylated species in pull downs from the indicated smc5-KE mutants, relative to wild-type controls from at least three independent experiments. Boxes, 25-75% data range; whiskers, total data range; black bar, median; grey cross, mean. ****P < 0.0001; ***P<0.001; **P < 0.01; *P<0.05. 1-way ANOVA, n = number of samples analyzed ",
    "ncbi_link": "smc5: 854123"
  },
  {
    "caption": " (D) Co-immunoprecipitation analysis of the Smc5-Nse2 interactions. NSE2-6HA cells were transformed with centromeric plasmids expressing the indicated SMC5 alleles, and protein extracts from exponentially growing cells subjected to anti-HA immunoprecipitation. A strain with no HA tag was used as control ",
    "ncbi_link": "NSE2: 856695
SMC5: 854123"
  },
  {
    "caption": " (E) Same as in (D), but using SMC6-6HA cells ",
    "ncbi_link": "SMC6: 851099"
  },
  {
    "caption": "A, Seedlings  of WT, abs3-1D, FD11-55, and arf2-20 before and after 6 d C-deprivation. B, Seedlings  of WT, abs3-1D, FD18-70, and pif5-10 before and after 6 d C-deprivation.",
    "ncbi_link": "abs3: 829035
arf2: 836321
pif5: 825075"
  },
  {
    "caption": "C and D, RT-qPCR  analysis of ABS3  expression levels in 7-d-old seedlings  of the same genotypes as shown in A (C) and B (D). Fold changes were calculated with respect to the expression level in the WT. two-tailed t test, ****, p<0.0001, n.s., not significant. data are means ± standard deviation (s.d.) of 3 biological replicates.",
    "ncbi_link": "ABS3: 829035"
  },
  {
    "caption": "G and H, RT-qPCR analysis of ORE1  and SGR1  expression levels in genotypes shown in A (G) and B (H) before and after 4 d C-deprivation. Fold changes were calculated with respect to the expression level in the WT before C-deprivation. data are means ± standard deviation (s.d.) of 3 biological replicates.",
    "ncbi_link": "ORE1: 833957
SGR1: 824589"
  },
  {
    "caption": "C, Heatmap of log2FC values of 2,587 ABS3-regulated genes (abs3-1D vs. WT) under C-deprivation  in indicated comparisons.",
    "ncbi_link": "ABS3: 829035
abs3: 829035"
  },
  {
    "caption": "F, Heatmap of log2FC values of 1,326 ARF2, PIF5, and C-deprivation co-regulated genes in indicated comparisons. C-deprivation: abs3-1D 4 d C-deprivation  vs. abs3-1D 0 d C-deprivation; ARF2: abs3-1D vs. arf2-20 abs3-1D after 4 d C-deprivation; PIF5: abs3-1D vs. abs3-1D pif5-10 after 4 d  C-deprivation. Enlarged were expression  changes of senescence genes identified in DAVID GO analysis",
    "ncbi_link": "abs3: 829035
ARF2: 836321
arf2: 836321
PIF5: 825075
pif5: 825075"
  },
  {
    "caption": "D,  Co-immunoprecipitation  of ARF2-HA  with PIF5-GFP  in vivo. ARF2-HA  was coexpressed with PIF5-GFP  or GFP  alone in protoplasts. Proteins co-immunoprecipitated  by GFP-Trap beads were immunoblotted  with anti-GFP  and anti-HA  antibodies.",
    "ncbi_link": "GFP: 
HA: 
ARF2: 836321
PIF5: 825075"
  },
  {
    "caption": "A, Seedlings  of WT, pARF2:ARF2-GFP  OEs in the WT background, pif4-2 pif5-10, and pARF2:ARF2-GFP  OEs in the pif4-2 pif5-10 background before and after 6 d C-deprivation.",
    "ncbi_link": "GFP: 
ARF2: 836321
pif4: 818903
pif5: 825075"
  },
  {
    "caption": "B,  RT-qPCR analysis of ARF2   expression levels in 7-d-old seedlings   of the same genotypes as shown in A. Fold changes were calculated with respect to the expression level in the WT. data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "ARF2: 836321"
  },
  {
    "caption": "D, Seedlings  of WT, pPIF5:PIF5-GFP  OEs in the WT background, arf2-20, and pPIF5:PIF5-GFP  OEs in the arf2-20 background before and after 6 d C-deprivation.",
    "ncbi_link": "GFP: 
arf2: 836321
PIF5: 825075"
  },
  {
    "caption": "E,  RT-qPCR analysis of PIF5  expression levels in 7-d-old seedlings  of the same genotypes as shown in D. Fold changes were calculated with respect to the expression level in the WT. data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "PIF5: 825075"
  },
  {
    "caption": "G, Seedlings  of WT, arf2-20, pif5-10, and arf2-20 pif5-10 before and after 12 d C-deprivation.",
    "ncbi_link": "arf2: 836321
pif5: 825075"
  },
  {
    "caption": "I, Seedlings of WT, abs3-1D, arf2-20 abs3-1D, pif5-10 abs3-1D, and arf2-20 pif5-10 abs3-1D before and after 8 d C-deprivation.",
    "ncbi_link": "abs3: 829035
arf2: 836321
pif5: 825075"
  },
  {
    "caption": "C, ChIP-qPCR  analysis of ARF2-GFP binding  to the promoters of ORE1  and SGR1  in the WT and pif4-2 pif5-10 backgrounds. In C fold enrichments were calculated with respect to the input. PP2A  served as a non-binding  control. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "ORE1: 833957
pif4: 818903
pif5: 825075
PP2A: 843333
SGR1: 824589"
  },
  {
    "caption": "D, RT-qPCR analysis of ORE1  and SGR1  expression levels in seedlings  of WT, pARF2:ARF2-GFP  OEs in the WT background, pif4-2 pif5-10, and pARF2:ARF2-GFP  OEs in the pif4-2 pif5-10 background before and after 4 d C-deprivation. Fold changes were calculated with respect to the expression level in the WT before C-deprivation. In D data are means ± s.d. of 3 biological replicates. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "GFP: 
ARF2: 836321
ORE1: 833957
pif4: 818903
pif5: 825075
SGR1: 824589"
  },
  {
    "caption": "E, ChIP-qPCR  analysis of PIF5-GFP binding  to the promoters of ORE1  and SGR1  in the WT and arf2-20 backgrounds. In fold enrichments were calculated with respect to the input. PP2A  served as a non-binding  control. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "arf2: 836321
ORE1: 833957
PP2A: 843333
SGR1: 824589"
  },
  {
    "caption": "F, RT-qPCR  analysis of ORE1  and SGR1  expression levels in seedlings  of WT, pPIF5:PIF5-GFP  OEs in the WT background, arf2-20, and pPIF5:PIF5-GFP  OEs in the arf2-20 background before and after 4 d C-deprivation. Fold changes were calculated as in D. In F, data are means ± s.d. of 3 biological replicates. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "GFP: 
arf2: 836321
ORE1: 833957
PIF5: 825075
SGR1: 824589"
  },
  {
    "caption": "G, Hypocotyl  elongation in seedlings  of WT, pPIF5:PIF5-GFP  OEs in the WT background, arf2-20, and pPIF5:PIF5-GFP  OEs in the arf2-20 background. Seedlings  were grown under continuous light for one week.",
    "ncbi_link": "GFP: 
arf2: 836321
PIF5: 825075"
  },
  {
    "caption": "H, RT-qPCR  analysis of PIL1  and YUC8  expression levels in seedlings  shown in G. Fold changes were calculated with respect to the expression level in the WT. Color legends in H are the same as in F. In H, data are means ± s.d. of 3 biological replicates. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "PIL1: 819311
YUC8: 828993"
  },
  {
    "caption": "J, ChIP-qPCR  analysis of PIF5 binding  to the promoters of PIL1  and YUC8  in the WT and arf2-20 backgrounds. In J, fold enrichments were calculated with respect to the input. PP2A  served as a non-binding  control. Data are means ± s.d. of 3 technical replicates. two-tailed t test, n.s., not significant, ****, p<0.0001. The experiment has been independently repeated with similar results.",
    "ncbi_link": "arf2: 836321
PIL1: 819311
PP2A: 843333
YUC8: 828993"
  },
  {
    "caption": "A, RT-qPCR analysis of ARF2  expression levels in 7-d-old seedlings  of WT, pARF2:ARF2-GFP  OEs in the WT background, mateq, and pARF2:ARF2-GFP  OEs in the mateq  background. Fold changes were calculated with respect to the expression level in the WT. B, RT-qPCR analysis of PIF5  expression levels in 7-d-old seedlings  of WT, pPIF5:PIF5-GFP  OEs in the WT background, mateq, and pPIF5:PIF5-GFP  OEs in the mateq  background. Fold changes were calculated as in A. In A, B, data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "GFP: 
ARF2: 836321
PIF5: 825075"
  },
  {
    "caption": "G and H, RT-qPCR analysis of ORE1  and SGR1  expression levels in genotypes shown in A (G) and B (H) before and after 4 d C-deprivation. Fold changes were calculated with respect to the expression level in the WT before  C-deprivation. Color legends in G are the same as in A. Color legends in are the same as in B. data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "ORE1: 833957
SGR1: 824589"
  },
  {
    "caption": "I,  RT-qPCR  analysis of PIL1  and YUC8  expression levels in 7-d-old seedlings  of the same genotypes as shown in B. Fold changes were calculated as in A. Color legends in I are the same as in B. data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "PIL1: 819311
YUC8: 828993"
  },
  {
    "caption": "B, ChIP-qPCR  analysis of ARF2-GFP binding  to the promoters of ABS3. Fold enrichments were calculated with respect to the input. PP2A  served as a non-binding control. Data are means ± s.d. of 4 technical replicates. The experiment has been independently repeated 3 times with similar results.",
    "ncbi_link": "ABS3: 829035
PP2A: 843333"
  },
  {
    "caption": "C, pABS3:GFP  or pABS3∆S2:GFP was expressed in WT mesophyll protoplasts with or without p35S:ARF2-HA. p35S:mCherry  was co-transfected and served as a transfection control. Protoplasts  were examined with fluorescence microscopy. Experiments were independently repeated 3 times with similar results. Bars, 100 μm. D, Dot plots of GFP  relative fluorescence intensity in protoplasts  expressing WT and mutant forms of pABS3:GFP  with or without p35S:ARF2-HA. Data are median with interquartile range, n is indicated in parentheses, two-tailed Mann-Whitney test, n.s., not significant, ****, p<0.0001.",
    "ncbi_link": "mCherry: 
GFP: 
HA: 
ABS3: 829035
ARF2: 836321"
  },
  {
    "caption": "E, RT-qPCR  analysis of ABS3  expression levels in 7-d-old seedlings  of WT, pARF2:ARF2-GFP  OEs in the WT background, pif4-2 pif5-10, and pARF2:ARF2-GFP  OEs in the pif4-2 pif5-10 background. Fold changes were calculated with respect to the expression level in the WT. Data are means ± s.d. of 3 biological replicates.",
    "ncbi_link": "GFP: 
ABS3: 829035
ARF2: 836321
pif4: 818903
pif5: 825075"
  },
  {
    "caption": "A In-vitro cell survival assay of HGSOC cell lines upon stable RAD51 overexpression. Mean with standard deviation is shown of at least three biological replicates per point. Extra-sum-of-squares F test.",
    "ncbi_link": "RAD51: 5888"
  },
  {
    "caption": "B In-vitro colony forming assays comparing RAD51-overexpressing and control HGSOC cell line, Caov-3, after treatment with increasing doses of carboplatin. Mean and SD of four biological replicates (left) a representative experiment (right). P-value for a comparison between cell lines for each drug treatment condition is indicated above the bars. T-test.",
    "ncbi_link": "RAD51: 5888"
  },
  {
    "caption": "Whole cell extracts of High Five insect cells individually expressing FLAG-SHLD3, Strep-RIF1, and 6xHis-REV7 through baculovirus infection were combined and subjected to FLAG immunoprecipitation or streptactin pulldown and immunoblotted for REV7 or the Strep or FLAG epitopes. Results are representative of three biologically independent experiments. IB: immunoblot, FL: full-length. For SHLD3, N and C correspond to residues 1-125 and 126-250, respectively.",
    "ncbi_link": "FLAG: 
His: 
Strep: 
REV7: 10459
RIF1: 55183
SHLD3: 112441434"
  },
  {
    "caption": "Representative micrographs of the LacR/LacO assay using mCherry-LacR-RIF1N as bait to evaluate chromatin recruitment of eGFP-tagged SHLD3 variants. SHLD3: residues 2-250. SHLD3N: residues 2-125. SHLD3C: residues 126-250. RIF1N: residues 1-967.",
    "ncbi_link": "mCherry: 
SHLD3: 
RIF1: 55183
SHLD3: 112441434"
  },
  {
    "caption": "Quantification of LacR/LacO assay measuring chromatin recruitment of eGFP-tagged SHLD3 variants to LacO arrays by mCherry-LacR-RIF1N. GFP intensities are presented as a ratio between the average fluorescence intensity within the mCherry-labeled LacR focus and the average nuclear intensity. Bars represent means (n = 138, 126, 129, 137 for eGFP, eGFP-SHLD3, eGFP-SHLD3N, eGFP-SHLD3C from 3 biologically independent experiments). Analysis was performed by Kruskal-Wallis test followed by Dunn's multiple comparisons against empty vector control or full-length eGFP-SHLD3. ****: P < 0.0001. ns: P > 0.05.",
    "ncbi_link": "eGFP: 
mCherry: 
SHLD3: 112441434"
  },
  {
    "caption": "Representative micrographs of the LacR-FokI assay to evaluate DNA damage recruitment of eGFP-tagged SHLD3 variants after induction of LacR-FokI expression.",
    "ncbi_link": "eGFP: 
FokI: 
SHLD3: 112441434"
  },
  {
    "caption": "Quantification of LacR-FokI assay evaluating recruitment of eGFP-tagged SHLD3 variants to FokI-induced DSBs at LacO arrays. GFP intensities are presented as a ratio between the average fluorescence intensity within the mCherry-labeled LacR-FokI focus and the average nuclear intensity. Bars represent mean (n = 143, 147, 147, 141 for eGFP, eGFP-SHLD3, eGFP-SHLD3N, eGFP-SHLD3C from 3 biologically independent experiments). Analysis was performed by Kruskal-Wallis test followed by Dunn's multiple comparisons against empty vector control or full-length eGFP-SHLD3. ****: P < 0.0001. ns: P > 0.05.",
    "ncbi_link": "eGFP: 
FokI: 
mCherry: 
SHLD3: 112441434"
  },
  {
    "caption": "Whole cell extracts of High Five insect cells individually expressing the wild-type (WT) or indicated alanine substitution FLAG-SHLD3C (residues 126-250) variants and Strep-RIF1N (residues 1-980) through baculovirus infection were combined and subjected to FLAG immunoprecipitation or streptactin pulldown and immunoblotted for the Strep or FLAG epitopes. The results are representative of two biologically independent experiments. IB: immunoblot. IP: immunoprecipitation.",
    "ncbi_link": "FLAG: 
Strep: 
RIF1: 55183
SHLD3: 112441434"
  },
  {
    "caption": "Quantification of LacR/LacO assay measuring recruitment of eGFP-SHLD3C wild-type (WT) or alanine substitution variants to LacO arrays in U2OS 2-6-3 cells by mCherry-LacR-RIF1N. GFP intensities are presented as a ratio between the average fluorescence intensity within the mCherry-labeled LacR-RIF1N focus and the average nuclear intensity. Bars represent means (n = 134, 125, 120, 130, 104, 129, 117 for EV, WT, S131A, W132A, R166A, N201A, D216A from 3 biologically independent experiments). EV: empty vector. Analysis was performed by Kruskal-Wallis test followed by Dunn's multiple comparisons against empty vector and WT controls. ****: P < 0.0001. ***: P = 0.0004. **: P = 0.002. *: P = 0.02. ns: P > 0.05.",
    "ncbi_link": "eGFP: 
mCherry: 
RIF1: 55183
SHLD3: 112441434"
  },
  {
    "caption": "Quantification of LacR-FokI assay measuring recruitment of eGFP-SHLD3C wild-type (WT) or alanine substitution variants to sites of DNA double-strand breaks induced by mCherry-LacR-FokI in U2OS 2-6-3 cells. GFP intensities are presented as a ratio between the average fluorescence intensity within the mCherry-labeled LacR-FokI focus and the average nuclear intensity. Bars represent means (n = 103, 136, 159, 151, 139, 145, 140 for EV, WT, S131A, W132A, R166A, N201A, D216A from 3 biologically independent experiments). Analysis was performed by Kruskal-Wallis test followed by Dunn's multiple comparisons against empty vector and WT controls. ****: P < 0.0001. ns: P > 0.05.",
    "ncbi_link": "eGFP: 
FokI: 
mCherry: 
SHLD3: 112441434"
  },
  {
    "caption": "Representative micrographs of immunofluorescence experiments (from 3 biologically independent experiments) analyzing localization of SHLD3 to 53BP1 bodies in RPE SHLD3-KO cells. 3xFLAG-SHLD3-complemented RPE SHLD3-KO cells were treated with 200 nM aphidicolin (Aphi) for 24 h and processed for immunofluorescence microscopy using antibodies against 53BP1, FLAG, and cyclin A. 53BP1 bodies are defined as distinct foci visible in cyclin A-negative cells. Quantification of FLAG and 53BP1 colocalization from A performed in CellProfiler. Pearson's correlation coefficients (PCC) were calculated for pixels within each cyclin A-negative, 53BP1 body-positive nucleus between the 53BP1 and FLAG channels. Each point represents the PCC value of an individual nucleus. Bars represent means. (n = 120, 130 for EV, SHLD3 from three biologically independent experiments). Analysis was performed using two-tailed Mann-Whitney test. ****: P < 0.0001.",
    "ncbi_link": "FLAG: 
SHLD3: 112441434"
  },
  {
    "caption": "Representative micrographs of immunofluorescence experiments analyzing localization of FLAG-SHLD3 alanine substitution variants stably expressed in RPE SHLD3-KO cells by lentivirus transduction. Cells were treated with 200 nM Aphi for 24 hours and processed for immunofluorescence microscopy using antibodies raised against 53BP1, FLAG, and cyclin A. 53BP1 bodies are defined as distinct foci visible in cyclin A-negative cells.",
    "ncbi_link": "FLAG: 
SHLD3: 112441434"
  },
  {
    "caption": "Quantification of the percentage of cells containing the indicated number of 53BP1 bodies in RPE WT and SHLD3-KO cells with or without 24-hour 200 nM Aphi treatment. Bars represent means ± s.d. (n = 3 biologically independent experiments with ≥ 30 nuclei imaged each).",
    "ncbi_link": "SHLD3: 112441434"
  },
  {
    "caption": "Left: Representation of the region of the RIF1 N-terminal HEAT repeats that is predicted to bind the SHLD3 eIF4E-like domain. Residues 1-173 are highlighted. Right: Quantification of LacR/LacO assay measuring eGFP-SHLD3 recruitment to LacO arrays in U2OS 2-6-3 cells by the indicated truncated mCherry-LacR-RIF1N variants. GFP intensities are presented as a ratio between the average fluorescence intensity within the mCherry-labeled LacR-RIF1N focus and the average nuclear intensity. Bars represent means (n = 148, 123, 122 for EV, 1-567, 174-567 from 3 biologically independent experiments). Analysis was performed using Mann-Whitney two-tailed test. ****: P < 0.001.",
    "ncbi_link": "GFP: 
mCherry: 
RIF1: 55183"
  },
  {
    "caption": "Whole cell extracts of High Five insect cells individually expressing the FLAG-SHLD3C (residues 126-250) and the indicated alanine substitution Strep-RIF1 (residues 1-980) variants through baculovirus infection were combined and subjected to FLAG immunoprecipitation or streptactin pulldown and immunoblotted for the Strep or FLAG epitopes. The results are representative of two biologically independent experiments. IB: immunoblot. IP: immunoprecipitation.",
    "ncbi_link": "FLAG: 
RIF1: 55183
SHLD3: 112441434"
  },
  {
    "caption": "Representative micrographs of UV laser microirradiation experiments measuring DNA damage recruitment of REV7 in U2OS 2-6-3 cells with endogenously mutated RIF1. DNA damage was induced in U2OS 2-6-3 cells through irradiation in the form of linear stripes and analyzed by immunofluorescence microscopy with RIF1 and REV7 antibodies. Quantification of UV laser microirradiation immunofluorescence experiment measuring DNA damage recruitment of REV7 in U2OS 2-6-3 cells with endogenously mutated RIF1. REV7 immunofluorescence intensities are presented as a ratio between the average fluorescence intensity within the RIF1-labeled irradiation stripe and the average nuclear intensity. Only nuclei containing RIF1 stripes are quantified. Bars represent means (n = 206, 215 for RIF1WT, RIF1D28N from 2 biologically independent experiments). Analysis was performed using Welch's t-test. ****: P < 0.0001.",
    "ncbi_link": "RIF1: 55183"
  },
  {
    "caption": "Quantification of class switch recombination in stimulated CH12F3 Shld3-/- cells stably expressing the indicated FLAG-SHLD3 variants through lentiviral transduction. Bars represent means ± s.d., n = 3 biologically independent experiments. Analysis was performed using one-way ANOVA followed by Dunnett's multiple comparisons test against Shld3-/- cells complemented with wild-type SHLD3. **: P < 0.01, *: P < 0.05, ns: P > 0.05.",
    "ncbi_link": "FLAG: 
Shld3: 113002583
SHLD3: 112441434"
  },
  {
    "caption": "Competitive growth assay of RPE BRCA1-KO SHLD3-KO cells complemented with 3xFLAG-SHLD3 variants. Growth of the indicated eGFP-expressing cells were compared to mCherry-expressing RPE BRCA1-KO SHLD3-KO cells transduced with empty vector after mixing 1:1 in 24-well plates. Plates were imaged 1, 5, 9, and 13 days after plating. Dotted black lines represent an eGFP:mCherry ratio of 1. Points represent means ± s.d. (n = 3 biologically independent experiments). Analysis was performed using a one sample t-test against a hypothetical eGFP:mCherry ratio value of 1 for the day 13 time point. **: P < 0.01, ns: P > 0.05.",
    "ncbi_link": "eGFP: 
FLAG: 
mCherry: 
BRCA1: 672
SHLD3: 112441434"
  },
  {
    "caption": "D Recombinant ALFY (aa 2981-3526) was incubated with GST‐Atg8 proteins conjugated to glutathione Sepharose. The pulled‐down complexes were subjected to SDS-PAGE and anti‐ALFY and anti‐GST immunoblotting. 5% of the recombinant ALFY protein used was loaded as input. Data are representative of three independent experiments.",
    "ncbi_link": "ALFY: 23001"
  },
  {
    "caption": "B 35S−labelled in vitro−translated GFP−ALFY (aa 2981-3526) wild−type and different LIR mutants were incubated with GST−GABARAP or −LC3C and binding evaluated by ARG. 10 and 2% of the in vitro−translated proteins used were loaded to illustrate binding affinity. CBB staining shows equal amounts of GST proteins used. Data are representative of three independent experiments.",
    "ncbi_link": "ALFY: 23001"
  },
  {
    "caption": "C MBP, MBP−ALFY (aa 3255-3526) or the ALFY−LIR mutant (F3346A) conjugated to amylose resins was incubated in the absence or presence of purified GABARAP. The pulled−down complexes were subjected to SDS-PAGE and visualized by CBB staining. Data are representative of three independent experiments.",
    "ncbi_link": "ALFY: 23001"
  },
  {
    "caption": "D GFP−LC3B and GFP−LC3B (Q26K/H27Y/H57D) were immunoprecipitated with GFP−TRAP® from total cell lysate of stably transfected HeLa FlpIn cells, followed by SDS-PAGE and immunoblotting with the indicated antibodies. Data are representative of three independent experiments.",
    "ncbi_link": "TRAP: 
LC3B: 81631"
  },
  {
    "caption": "E MBP‐ALFY3255-3526 conjugated to amylose resin was incubated with GST or the indicated GABARAP mutants. The pulled‐down complexes were subjected to SDS-PAGE and visualized by immunoblotting with anti‐MBP and anti‐GABARAP antibodies. Data are representative of three independent experiments.",
    "ncbi_link": "GABARAP: 11337"
  },
  {
    "caption": "F MBP−tagged ALFY3255-3526 and p62168-391 or their corresponding LIR mutants (F3346A and W340A, respectively) were conjugated to amylose resin and incubated with purified GST, GABARAP, GABARAP mutant (K24Q/Y25H/D54H), LC3B or LC3B mutant (Q26K/H27Y/H57D). The bound proteins were visualized by immunoblotting with anti−GABARAP, anti−LC3 and anti−MBP antibodies. Data are representative of three independent experiments.",
    "ncbi_link": "GABARAP: 11337
LC3B: 81631
p62: 8878"
  },
  {
    "caption": "B GFP−tagged full−length ALFY wild−type or LC3−interacting region (LIR)−mutant was expressed into Alfy−deficient MEFs using an adenovirus system. At 48 h after infection, the MEFs were cultured in normal media or EBSS for 1.5 h before staining with anti−LC3B or anti−GABARAP antibodies. Scale bars 10 μm.",
    "ncbi_link": "LC3: 67443///66734
ALFY: 72145
Alfy: 72145"
  },
  {
    "caption": "C HeLa cells were treated with control or siRNA targeting GABARAP, GABARAPL1 and GABARAPL2. 72 h after transfection cells were immunostained with anti−LC3B, anti−ALFY and anti−p62 antibodies. Scale bars, 10 μm.",
    "ncbi_link": "GABARAP: 11337
GABARAPL1: 23710
GABARAPL2: 11345"
  },
  {
    "caption": "B. Flow cytometry for Bu-1a expression in wild type cells with (GAA)n tracts of different length knocked into the BU-1A locus (in blue). DT40 cells are heterozygous and carry one BU-1A and one BU-1B allele. All experiments introducing repeats into BU-1A are carried out in cells in which the +3.5 G4 has been deleted from both A and B alleles, to avoid transvection between the allele Black outline: positive control (wild type cells); red outline: negative control (cells carrying a genetic disruption of BU-1)",
    "ncbi_link": "BU-1: 396098
BU-1A: 396098
BU-1B: 396098"
  },
  {
    "caption": "C, D. Bu-1a fluctuation analysis of wildtype and primpol cells in which the endogenous +3.5 G4 has been deleted (ΔG4) or with (GAA)10 and (GAA)20 sequence orientated such that it is replicated as the leading (C) or lagging (D) strand template for a fork entering from the 3' end of the locus as shown in panel (A). At least two independent fluctuation analyses were performed. Circles represent the percentage of Bu-1a loss variants in at least 24 individual clones from these experiments, with mean ± SD reported. ****p < 0.0001, * p ≤ 0.05, ns = not significant; one-way ANOVA.",
    "ncbi_link": "Bu-1a: 396098
primpol: 422549"
  },
  {
    "caption": "Human PrimPol, or mutants, tagged with YFP were expressed in primpol cells harbouring (GAA)10 sequence in the BU-1A locus. Bu-1a and YFP double positive cells were sorted and expanded for 2 weeks, and then analysed for Bu-1a expression variants. For each complementation, at least two independently derived clones were subjected to fluctuation analysis. As previously observe expression of hPrimPol[AxA] and hPrimPol[ZfKO] is deleterious and unstable. Cells expressing these mutations and remaining YFP-positive at the end of the expansion period will have been through fewer divisions the other lines in this analysis. Pooled results from at least three independent fluctuation analyses are represented with mean ±SD indicated with red bar and whiskers. Statistical significance: **** p < 0.0001, *** p<0.001, * p ≤ 0.05, ns = not significant; Kruskal-Wallis test",
    "ncbi_link": "YFP: 
BU-1A: 396098
Bu-1a: 396098
hPrimPol: 201973
PrimPol: 201973
primpol: 422549"
  },
  {
    "caption": "A. DRIP-qPCR analysis reveals accumulation of R-loops across the BU-1 locus in primpol cells. The DRIP signal was calculated as enrichment over RNase H-treated samples and was normalised to -0.5 kb amplicon. The mean and SD for three biological replicates is presented. An unpaired t-test was used to compare differences between matched amplicons in primpol BU-1A(GAA)10 and the other cell lines indicated. **** p ≤ 0.0001, ns = not significant",
    "ncbi_link": "BU-1: 396098
BU-1A: 396098
primpol: 422549"
  },
  {
    "caption": "B. DNA:RNA hybrids in primpol BU-1A(GAA)10:GgRNase H and primpol BU-1A(GAA)10:hPrimPol. An unpaired t-test on three biological replicates was used to compare differences to primpol BU-1A(GAA)10 for each matched amplicon. The bar represent the mean and whiskers the SD. *** p ≤ 0.001, ** p ≤ 0.01, ns = not significant",
    "ncbi_link": "BU-1A: 396098
hPrimPol: 201973
primpol: 422549
GgRNase H: 395848"
  },
  {
    "caption": "C. Overexpression of chicken RNase H1 prevents (GAA)10 induced BU-1A epigenetic instability in primpol cells. Fluctuation analysis was performed on three primpol BU-1A (GAA)10 clones. One-way ANOVA was used to calculate the significance of differences in BU-1 instability between primpol BU-1A ΔG4 and other cell lines. **** p ≤ 0.0001, ns = not significant",
    "ncbi_link": "BU-1: 396098
BU-1A: 396098
primpol: 422549
RNase H1: 395848"
  },
  {
    "caption": "E. R-loop stabilisation induces epigenetic instability of BU-1. Bu-1a fluctuation analysis of wild type cells expressing HBD-mCherry. The scatter plots pool results from at least two different clones with matched HBD-expression. Mean ± SD reported. **** p ≤ 0.0001, *** p ≤ 0.001, ns = not significant; one-way ANOVA.",
    "ncbi_link": "BU-1: 396098
Bu-1a: 396098"
  },
  {
    "caption": "B. Bu-1a fluctuation analysis of two independently derived primpol BU-1A(GAA)10: Gg RNase H1-YFP-geminin degron clones. Since the expression of the RNase H1-YFP-geminin degron construct is not stable (unlike the RNase H1-YFP construct without the degron), Bu-1a expression was assessed separately in the YFP +ve and YFP -ve cells within each clone. Statistical differences calculated the Kruskal-Wallis test. For all panels, at least 36 individual clones were analysed; mean ± SD reported. **** p ≤ 0.0001, *** p ≤ 0.001, ns = not significant",
    "ncbi_link": "Bu-1a: 396098
BU-1A: 396098
primpol: 422549
RNase H1: 395848"
  },
  {
    "caption": "C. DRIP-qPCR for R-loops around the engineered +3.5 (GAA)10 repeat in BU-1 in different phases of the cell cycle. The location of the qPCR amplicons is indicated in the map at the top of the panel. The BU-1 DRIP signal was normalised to -0.5 kb amplicon in G1-arrested cells (t = 0 h) Black: wild type; red: primpol. Error bars = SD. **** p ≤ 0.0001, *** p ≤ 0.001, ** p ≤ 0.01, * p ≤ 0.05",
    "ncbi_link": "BU-1: 396098
primpol: 422549"
  },
  {
    "caption": "E. Validation of analysis of nascent DNA:RNA hybrid formation in BU-1 locus. Enrichment of 4SU labelled RNA moiety of DNA:RNA hybrids was calculated relative to input in three independent asynchronous wild type (black) or primpol (red) cells, with or without exogenous RNase H treatment. Error bars = SD. ** p ≤ 0.01, * p ≤ 0.05, ns = not significant; unpaired t-test",
    "ncbi_link": "BU-1: 396098
primpol: 422549"
  },
  {
    "caption": "G. Newly synthesised R-loops in BU-1 during S phase in wild type (black) and primpol (red). Error bars represent 1SD of three biological repeats of the experiment. *** p ≤ 0.001, * p ≤ 0.05; unpaired t-test",
    "ncbi_link": "BU-1: 396098
primpol: 422549"
  },
  {
    "caption": "A. Representative normalised DRIP-seq data in two genes COL22A1, spanning over 200 kb, and MYC. The locations of H-DNA and G4 motifs are shown below the gene map. Wild type in blue; primpol in red. The corresponding RNAse H-treated samples are dashed. See Methods for further details of graphic generation. Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "COL22A1: 420315
MYC: 420332
primpol: 422549
RNAse H: 395848"
  },
  {
    "caption": "C. DRIP peak heights in wild type and primpol DT40 normalised to Drosophila S2 spike-in. n (wild type) = 41445; n (primpol) = 48648. D. Correlation of normalised DRIP peak heights in the overlapping peaks between wild type and primpol. Blue line = 1:1 correlation; red line = linear regression through data. Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 422549"
  },
  {
    "caption": "E. Correlation between H-DNA forming sequences and all genes (white bar), and genes with DRIP peaks in wild type (blue) and primpol cells (red). F. Normalised DRIP peak heights in the genes identified as associating with H-DNA. Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 422549"
  },
  {
    "caption": "G. Correlation between G4 motifs ([G3-5N1-7]4) and all genes (white bar), and genes with DRIP peaks in wild type (blue) and primpol cells (red). H. Normalised DRIP peak heights in the genes identified as associating with G4 motifs ([G3-5N1-7]4). Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 422549"
  },
  {
    "caption": "A. Representative normalised RNA DIP-seq data in the SKI locus. Wild type in blue; primpol in red. The locations of H-DNA and G4 motifs are shown below the gene map. The corresponding RNAse H-treated samples are dashed. Since so little material was recovered following RNase H treatment, all samples were pooled prior to library generation. Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 201973
RNAse H: 246243
RNase H: 246243
SKI: 6497"
  },
  {
    "caption": "C. RNA DIP-seq peak heights in wild type and primpol BOBSC cells normalised to a DT40 spike-in. n (wild type) = 32740; n (primpol) = 33721. D. Correlation of normalised RNA DIP-seq peak heights in the overlapping peaks between wild type and primpol. Blue line = 1:1 correlation; red line = linear regression through data. Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 201973"
  },
  {
    "caption": "E. Correlation between H-DNA forming sequences and all genes (white bar), and genes with DRIP peaks in wild type (blue) and primpol cells (red). Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 201973"
  },
  {
    "caption": "F. Correlation between G4 motifs ([G3-5N1-7]4) and all genes (white bar), and genes with DRIP peaks in wild type (blue) and primpol cells (red). Data information: P values calculated with Mann-Whitney U test. In violin plots, bar = median; box = interquartile range (IQR); whiskers = upper and lower inner fences (1st / 3rd quartile + 1.5*IQR).",
    "ncbi_link": "primpol: 201973"
  },
  {
    "caption": "Western blot images of Trf1lox/lox MEFS with or without overexpression of eGFP-Trf1 WT or mutant alleles followed by Cre recombinase transduction.",
    "ncbi_link": "eGFP: 
Cre recombinase: 2777477
Trf1: 21749"
  },
  {
    "caption": "Quantification of eGFP-TRF1 inhibition in Trf1Δ/Δ MEFs transduced with eGFP-Trf1 WT or mutant alleles as indicated. Data are representative of n=15 biological replicates",
    "ncbi_link": "eGFP: 
Trf1: 21749"
  },
  {
    "caption": "Growth curves of Trf1Δ/Δ MEFs transduced with eGFP-Trf1 WT or mutant alleles as indicated. Data are representative of n=5 biological replicates",
    "ncbi_link": "eGFP: 
Trf1: 21749"
  },
  {
    "caption": "Western blot images of Trf1lox/lox MEFS with or without overexpression of eGFP-Trf1 WT or mutant alleles followed by Cre recombinase transduction. Quantification of eGFP-TRF1 inhibition in Trf1Δ/Δ MEFs transduced with eGFP-Trf1 WT or mutant alleles as indicated. Data are representative of n=5 biological replicates",
    "ncbi_link": "eGFP: 
Cre recombinase: 2777477
Trf1: 21749"
  },
  {
    "caption": "Western blot images of p53-/- MEFS with or without overexpression of eGFP-Trf1 WT or mutant alleles followed treatment with ERKi. Data are representative of n=2 biological replicates",
    "ncbi_link": "eGFP: 
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Representative images (above) and percentage (bottom) of Telomeric and 53BP1 colocalizing foci (TIFs) per cells of p53-/- MEFS with or without overexpression of eGFP-Trf1 WT and the indicated mutants upon treatment with the ERKi. White arrowheads: colocalization of telomeric and 53BP1. Scale bars, 10μm.",
    "ncbi_link": "eGFP: 
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Western blot image (above) and quantification (bottom) of TRF1 protein levels upon genetic depletion of ERK1/2 in p53-/- MEF line. Data are representative of n=3 independent experiments.",
    "ncbi_link": "ERK1: 26417
p53: 22059"
  },
  {
    "caption": "Representative images (above) and quantification (bottom) of TRF1 telomeric foci in ERK1/2 RNA interfered p53-/- MEFs. Scale bars, 5μm. Data are representative of n=2 independent experiments.",
    "ncbi_link": "ERK1: 26417
p53: 22059"
  },
  {
    "caption": "Western blot image of eGFP-tagged and endogenous TRF1 protein levels upon genetic depletion of ERK1/2 in p53-/- MEF line.",
    "ncbi_link": "ERK1: 26417
p53: 22059"
  },
  {
    "caption": "Representative images (above) and percentage (bottom) of telomeric and 53BP1 colocalizing foci (TIFs) per cell in p53-/- MEF with or without overexpression of eGFP-Trf1 WT and indicated mutants upon genetic depletion of ERK1/2. White arrowheads: colocalization of telomeric and 53BP1.Scale bars, 10μm.",
    "ncbi_link": "eGFP: 
ERK1: 26417
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Knockdown of HER3 in BT474 cells. Control and HER3-targeted short hairpin sequences were transduced in BT474 cells and HER3, pHER3 and pAKT levels analyzed by Western. Levels of pHER3 were analyzed by a specific anti-pHER3 antibody.",
    "ncbi_link": "HER3: 2065"
  },
  {
    "caption": "Effect of HER3 knockdown on the antiproliferative action of EV20/MMAF analyzed by cell counting after 5 days of treatment with the ADC.",
    "ncbi_link": "HER3: 2065"
  },
  {
    "caption": "Western blot analysis of TEX11 in the testes of 3-month-old mice with different Tex11 gene dosages. ACTB serves as a loading control.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "Histological analysis of testes from adult wild-type, Tex11 KI/KO, and Tex11−/Y males. RS, round spermatids; ES, elongating spermatids; Pa, pachytene spermatocytes. Scale bar, 50 μm.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "The Tex11 knockin allele rescues chromosomal synapsis defects in Tex11−/Y spermatocytes in 3-month-old males. Chromosomal synapsis defects were assessed by SYCP1 and SYCP2 immunostaining of spread nuclei from 100 pachytene spermatocytes per male; for each genotype, three males were analyzed. Abbreviations for Tex11 genotypes: −/Y, Tex11 knockout (Yang et al, 2008); KI;−/Y, Tex11 knockin and knockout; +/Y, wild type; KI;+/Y, Tex11 knockin plus wild-type Tex11.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "Reduced testis weight in juvenile but not adult Tex11 KI; −/Y males. The time frames of the first wave and adult waves of spermatogenesis are indicated.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "Increased chromosomal asynapsis in spermatocytes and reduced levels of TEX11 protein in the testes of 25-day-old Tex11 KI/KO males. Chromosomal synapsis defects were assessed by SYCP1 and SYCP2 immunostaining of spread nuclei from 100 pachytene spermatocytes per male; for each genotype, three males were analyzed.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "Pachytene spermatocytes from 25-day-old Tex11 KI/KO males contain significantly fewer MLH1 foci compared to wild-type spermatocytes. Values are shown as average ± standard deviation. Error bar is standard deviation.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "The number of MLH1 foci in pachytene spermatocytes from 3-month-old males positively correlates with increasing Tex11 gene dosage.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "Quantification of MLH1 foci in pachytene oocytes from the ovaries of Tex11−/−, Tex11+/−, and wild-type embryonic day-17.5 (E17.5) fetuses reveals a positive correlation of Tex11 gene dosage and the number of MLH1 foci.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "B-D Body weight (B), testisweight (C) in Tex11 KI(V749A)/KO males.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "B-D Significantly reduced sperm count (per pair of epididymides) in Tex11 KI(V749A)/KO males (D).",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "F Dramatically increased chromosomal asynapsis in spermatocytes from Tex11 KI(V749A)/KO males. 100 pachytene spermatocytes per mouse were examined by surface spread analysis.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "B. A549 cells infected with ZIKV (MOI=3) for 6 hrs were transfected with 2 μg poly(I:C) for 12 hrs after which levels of ifn-",
    "ncbi_link": "ifn-: 3456"
  },
  {
    "caption": "C. A549 cells were infected with ZIKV (MOI=5) for 16 hrs and then transfected with an IFIT1 promoter-driven firefly luciferase plasmid (pGL3B/561) and a constitutively active renilla luciferase construct (pRL-TK), as well as 1 μg of poly(I:C). Eight hours later cell lysates were harvested and subjected to luciferase assay. Values are expressed as mean of two independent experiments, N=2",
    "ncbi_link": "firefly: 
renilla: 
IFIT1: 3434"
  },
  {
    "caption": "D. HEK293T cells were transfected with plasmids encoding each of the 10 ZIKV proteins. Sixteen hours later they were transfected with an IFIT1 promoter-driven firefly luciferase plasmid (pGL3B/561) and a constitutively active renilla luciferase construct (pRL-TK), as well as 1 μg of poly(I:C). Eight hours later cell lysates were harvested and subjected to luciferase assay. C = capsid; E = envelope. Values are expressed as mean ± standard error. *P<0.05, **P<0.01 (Student's t-test), N=4",
    "ncbi_link": "firefly: 
renilla: 
IFIT1: 3434"
  },
  {
    "caption": "E. A549 cells were infected with ZIKV (MOI=5) for 16 hrs and then transfected with the indicated promoter-driven firefly luciferase plasmids and a constitutively active renilla luciferase construct (pRL-TK), as well as 1 μg of poly(I:C). Eight hours later cell lysates were harvested and subjected to luciferase assay. Values are expressed as mean of two independent experiments, N=2",
    "ncbi_link": "firefly: 
renilla: "
  },
  {
    "caption": "F. HEK293T cells were transfected with plasmids encoding individual ZIKV proteins, the indicated promoter-driven firefly luciferase plasmids and a constitutively active renilla luciferase construct (pRL-TK), as well as 0.4 μg of poly(I:C). Twenty-four hours later cell lysates were harvested and subjected to luciferase assay. C = capsid; E = envelope. Values are expressed as mean ± standard error. *P<0.05, **P<0.01 (Student's t-test); N=3",
    "ncbi_link": "firefly: 
renilla: "
  },
  {
    "caption": "B. A549 cells were infected with ZIKV (MOI=3) for 6 hrs prior to addition of IFN-α (100 U/mL), IFN-λ (200 ng/mL) or IFN-γ (10 U/mL) for 12 hrs. Total RNA was isolated and levels of ifit1 RNAs were determined by qRT-PCR. Values are expressed as mean ± standard error. *P<0.05, **P<0.01 (Student's t-test); N=3",
    "ncbi_link": "ifit1: 3434"
  },
  {
    "caption": "C. A549 cells were infected with ZIKV (MOI=5) for 6 hrs and then transfected with ISRE- or GAS- promoter-driven firefly luciferase together with a constitutively active renilla luciferase construct. Sixteen hours later, cells were treated with IFN-α (100 U/ml) or IFN-α (10 U/ml) for 2 hrs. Cells lysates were harvested and relative luciferase activity from ISRE- and GAS-promoters were determined. Values are expressed as mean ± standard error. *P<0.05 (Student's t-test); N=3",
    "ncbi_link": "firefly: 
renilla: "
  },
  {
    "caption": "D. HEK293T cells were transfected with ZIKV protein expression constructs together with an ISRE promoter-driven firefly luciferase plasmid (pGL3B/561) and a constitutively active renilla luciferase construct (pRL-TK). After 24 hrs they were treated with IFN-α (100 U/mL) for 10 hrs. Cell lysates were then harvested and subjected to luciferase assays. C = capsid; E = envelope. Values are expressed as mean ± standard error. *P<0.05 (Student's t-test); N=3",
    "ncbi_link": "firefly: 
renilla: "
  },
  {
    "caption": "E. STAT2 levels in MEFs were decreased by transfection with siRNAs for 48 hrs after which the cells were infected with ZIKV (MOI=5) for another 48 hrs. The ZIKV replication was measured by qRT-PCR.",
    "ncbi_link": "STAT2: 20847"
  },
  {
    "caption": "A. A549 cells were transfected with control plasmid pcDNA 3.1 or plasmids encoding FLAG-tagged WT or mutant NS5 proteins. At 48 hrs post-transfection cells were treated with IFN-α (100 U/mL) for 2 hrs and then processed for indirect immunofluorescence. Images were acquired on a spinning disk confocal microscope with a 40X objective. NS5 positive cells are indicated by dashed white circles. Representative panels are shown. The experiment was repeated three times.B. Quantification of nuclearSTAT2 was performed using Volocity image analyses software. A minimum of 20 cells were counted for each sample. N.D.= not detected. Values are expressed as mean ± standard error. *P<0.05, **P<0.01 (Student's t-test); N=3",
    "ncbi_link": "NS5: 7751225"
  },
  {
    "caption": "C. A549 cells were transfected with plasmids encoding FLAG-tagged ZIKVNS5 or FLAG alone for 24 hrs and then treated with epoxomicin (400 nM) for 24 hrs. Cells were harvested and process for immunoprecipitation (IP) using a mouse anti-FLAG or anti-myc antibody followed by SDS-PAGE and Immunoblotting. Representative panels are shown. The experiment was repeated three times.",
    "ncbi_link": "NS5: 7751225"
  },
  {
    "caption": "D. A549 cells were transfected with plasmids encoding FLAG-tagged WT, mutant NS5 proteins or FLAG alone for 48 hrs. Cells were harvested and process for immunoprecipitation (IP) using rabbit anti-STAT2 followed by SDS-PAGE and immunoblotting. Arrows indicate co-immunoprecipitated WT NS5 and NS5 mutants that are in a complex with STAT2. Representative panels are shown. The experiment was repeated two times.",
    "ncbi_link": "NS5: 7751225"
  },
  {
    "caption": "Immunofluorescence image of R26Fucci2a x Dermo1Cre back skin at P2 where mVenus-hGem (green) expressing cells are in S/G2/M phase and mCherry-hCdt1 (red) positive cells are arrested in G1 phase. Percentage of labelled cells in S/G2/M cell cycle phase in the upper and lower dermis at P0 (n=3 biological replicates) and P2 (n=4 biological replicates).",
    "ncbi_link": "Fucci2a: 
Cre: 2777477
Dermo1: 13345"
  },
  {
    "caption": "In vivo lineage tracing of upper (Blimp1Cre) and lower (Dlk1CreER) dermal fibroblasts during wound healing. Immunofluorescence image of Blimp1Cre x Confetti (upper panels) and Dlk1CreER x Confetti (lower panel) back skin inside and outside the wound bed at 10 days post wounding. Colours show YFP (green), RFP (red) and CFP (blue) with bright field image overlaid. (G) Clone size quantification of Blimp1Cre labelled fibroblasts inside and outside the wound bed at 10 days post wounding (n= 400 clones of 4 biological replicates). (H) Clone size quantification of Blimp1Cre labelled fibroblasts inside and outside the wound bed at 10 days post wounding (n=300 clones of 2 biological replicates).",
    "ncbi_link": "Cre: 2777477
CreER: 2777477
Dlk1: 13386
Blimp1: 12142"
  },
  {
    "caption": "(B-C) Western blot analysis (B) and densitometric quantification (C) of OTUD1 in aortas of control and Ang II-induced mice. β-actin was used as the loading control (n=5 biological replicates). (D) mRNA levels of OTUD1 in aortas of control and Ang II-induced mice were determined by RT-qPCR. The values were normalized to Rn18s (n=5 biological replicates).",
    "ncbi_link": "OTUD1: 71198
Rn18s: 19791"
  },
  {
    "caption": "(G-H) mRNA levels of Cdh5, Vim, Twist1, Snai1 (G), Tgfb1 and Col1a1 (H) in aortic tissues of the mice were examined by real-time qPCR assay. The values were normalized to Rn18s (n=5 biological replicates).",
    "ncbi_link": "Cdh5: 12562
Col1a1: 12842
Rn18s: 19791
Snai1: 20613
Tgfb1: 21803
Twist1: 22160
Vim: 22352"
  },
  {
    "caption": "(B) HUVECs transfected with si-OTUD1 or NC were challenged with 1 μM Ang II for 24 h. Western blot analysis of VE-cadherin, Vimentin, α-SMA, Twist and Snail were performed. GAPDH was used as the loading control.",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": "(E) HUVECs transfected with Flag-OTUD1 or EV were challenged with 1 μM Ang II for 24 h. Western blot analysis of VE-cadherin, Vimentin, α-SMA, Twist and Snail were performed. GAPDH was used as the loading control.",
    "ncbi_link": "Flag: 
OTUD1: 220213"
  },
  {
    "caption": "(C) Co-immunoprecipitation of OTUD1 and SMAD2 or SMAD3 in HUVECs transfected with Flag-OTUD1. Exogenous Flag-OTUD1 was immunoprecipitated by anti-Flag antibody. IgG, immunoglobulin G.",
    "ncbi_link": "Flag: 
OTUD1: 220213"
  },
  {
    "caption": "(G) Immunoprecipitation of SMAD3 in 293T cells co-transfected with GFP-SMAD3, HA-Ub and Flag-OTUD1 and then challenged with 10 μM MG132 for 6 h. Ubiquitinated SMAD3 was detected by immunoblotting using anti-HA antibody. (H) Immunoprecipitation of SMAD3 in 293T cells co-transfected with GFP-SMAD3, HA-Ub, and Flag-OTUD1 or Flag-OTUD1(C320S), and then challenged with 10 μM MG132 for 6 h. Ubiquitinated SMAD3 was detected by immunoblotting using anti-HA antibody. (I) Immunoprecipitation of SMAD3 in 293T cells co-transfected with GFP-SMAD3, Flag-OTUD1, and HA-Ub, HA-Ub-K48 (K48 only), or HA-Ub-K63 (K63 only), respectively, and then challenged with 10 μM MG132 for 6 h. Ubiquitinated SMAD3 was detected by immunoblotting using anti-HA antibody.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
OTUD1: 220213
SMAD3: 4088
Ub: 7316///7314"
  },
  {
    "caption": "(A-B) 293T cells were transfected with various amount of Flag-OTUD1. Western blot analysis (A) and densitometric quantification (B) of SMAD3. GAPDH was used as the loading control (n=3 biological replicates).",
    "ncbi_link": "Flag: 
OTUD1: 220213"
  },
  {
    "caption": "(G) Co-immunoprecipitation of SMAD3 and SMAD4 in 293T cells co-transfected with GFP-SMAD3, HA-Ub, and HA-Ub-K63 (K63 only), respectively, and then challenged with 10 μM MG132 for 6 h. Exogenous SMAD3 was immunoprecipitated by anti-GFP antibody.",
    "ncbi_link": "GFP: 
HA: 
SMAD3: 4088
Ub: 7316///7314"
  },
  {
    "caption": "(H) Co-immunoprecipitation of SMAD3 and SMAD4 in 293T cells co-transfected with GFP-SMAD3 and Flag-OTUD1 and then challenged with 10 μM MG132 for 6 h. Exogenous SMAD3 was immunoprecipitated by anti-GFP antibody. IgG, immunoglobulin G.",
    "ncbi_link": "Flag: 
GFP: 
OTUD1: 220213
SMAD3: 4088"
  },
  {
    "caption": "A. Representative pseudo colour images of sypHy    fluorescence in WT and BsnGT hippocampal neurons at rest, upon stimulation with 40 and 900 APs at 20Hz (in the presence of bafilomycin A1) and upon application of NH4Cl to visualise SVs  that were refractory to electrical stimulation. B. Average traces of the normalised fluorescence change (ΔF/F0) of sypHy    in WT (black) and  BsnGT (red) neurons  as described in A. Intensities were normalized to the peak of NH4Cl response. C. Quantifications of mean RRP   fraction in WT and BsnGT. D. Frequency distribution histograms of the response amplitudes of 1050 individual synaptic  puncta (from 6 independent experiments) to stimulation with 40 AP. The distribution is shifted to lower values in BsnGT. E. Quantifications of mean TRP   fraction in WT and BsnGT. F. Frequency distribution histograms of synaptic  response amplitudes in BsnGT and WT neurons  stimulated with 900 AP. Note the shift in distribution between genotypes. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers, and + indicates mean. In the frequency distribution histograms (D and F) black lines depict superimposed Gaussian fits for each group. The sample size n (in parentheses) corresponds to the number of analysed imaging experiments (B, C, E) In D and F, the data of 1050 synapses per genotype were processed. Data is obtained from 6 (A-F) independent culture preparations. Significance was assessed with Student's t-test; *** p < 0.001. Scale bar is 2 µm in A",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "G, Representative images of Syt1Ab  uptake (magenta) driven by endogenous network activity in  hippocampal neurons (18 DIV) from WT and BsnGT mice. VGLUT1  (green) marks  excitatory presynapses  (upper panels) and VGAT   the inhibitory  ones (lower panels). H. Quantification of normalized IF  of Syt1Ab  uptake in excitatory  (red boxes) and inhibitory  (pink boxes) synapses  on experiments in G. I. Quantification of fraction of active (Syt1Ab-labelled) excitatory  and inhibitory synapses on experiments illustrated in G. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers, and + indicates mean. The dashed lines in H depict IF  in WT that were used for normalization. The sample size n (in parentheses) corresponds to the number of analysed images (G, Data is obtained from independent culture preparations. Significance was assessed with Student's t-test; *** p < 0.001. Scale bar is 5 µm in G",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A, B. Representative pseudo colour images (A) and average traces (B) of sypHy  fluorescence plotted for WT and BsnGT neurons  treated with a CDK5  inhibitor roscovitine  (rosc, 100µM, gray and pink trace) or vehicle (black and red trace) for 30 minutes before stimulation with 40 and 900 APs in the presence of  bafilomycin A. C, D. Plots show mean values of RRP  (C) and TRP  (D) fraction for both genotypes before and after treatment. E. Roscovitine  treatment has a significantly higher effect on RRP  and TRP  in BsnGT neurons compared to WT. Data information: n corresponding to the number of imaging experiments done on 4 independent cell preparations is given in brackets for each analysis. In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers, and + indicates mean. Significance was assessed by two-way ANOVA with Tukey´s multiple comparison test (C, D) and by Student's t-test (E) *p≤0.05, **p < 0.01, ***p< 0.001. Scale bar is 2µm.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A. Representative immunoblot  with antibody against CDK5-dependent pSer551 of Syn1  (pSer551Syn1) and total Syn1  and total protein stain  used as loading control for quantification of Syn1  on P2 fractions prepared from hippocampal  tissue lysates of WT and BsnGT mice. B, C. Quantification of pSer551Syn1 / Syn1  ratio (in B) and total Syn1  (in C) abundance on blots  from A. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers and + indicates mean. The sample size n (in brackets) corresponds to the number of independently processed animals in B and C For statistics, student's t-test in B and C were used, *p≤0.05, **p < 0.01, ***p< 0.001.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "E. Representative images of 19 DIV cultured hippocampal neurons from WT and BsnGT immunostained  for pSer551Syn1  and total Syn1. F. Quantification of IF  intensity of pSer551Syn1 in synapses  from WT,  BsnGT, and WT cells treated with roscovitine. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers and + indicates mean. The sample size n (in brackets) corresponds to the number of independent images (E, quantified from two (F) independent cultures per condition. For statistics, one-way ANOVA with Sidak´s multiple comparisons test in F were used, *p≤0.05, **p < 0.01, ***p< 0.001. Scale bar is 5 µm in",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "G. Representative images of 21 DIV hippocampal WT and BsnGT neurons  at baseline activity, upon network activity silencing (TTX, 1 µM, 72 h) or in conditions of increased activity (BIC, 30 µM, 48 h) H. Quantification of experiment in G. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers and + indicates mean. The sample size n (in brackets) corresponds to the number of independent images , G) quantified from four (H) independent cultures per condition. For statistics two-way ANOVA with Tukey´s multiple comparisons test in H were used, *p≤0.05, **p < 0.01, ***p< 0.001. Scale bar is 5 µm in G.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A, B. Representative pseudo colour images (A) and average traces (B) of sypHy  fluorescence plotted from WT and  BsnGT hippocampal neurons treated with calcineurin  inhibitor FK506. Data information: Scale bar is 2 µm.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "C, D. Quantification of the RRP  and TRP  fractions in WT and  BsnGT neurons  from experiment in A, B. Data information: In all plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers, and + indicates mean. The sample size is given in brackets for each quantification and reflect the number of analysed imaging experiments done on 3 independently prepared cultures per genotype Statistical significance was assessed using two-way ANOVA with Tukey´s multiple comparison test for C and D significance is depicted as follows: *p≤0.05, **p < 0.01, ***p< 0.001.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "E. Representative Western blot  on P2 fractions prepared from hippocampal  tissue of WT and BsnGT mice  probed with antibodies against SNAP25 phosphorylated  onThr138 and total SNAP25. F. Quantification of blot  in E shows lower pThr138SNAP25 to total SNAP25 IF  ratio in BsnGT compared to WT. Data information: In all plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers, and + indicates mean. The sample size is given in brackets for each quantification and reflect the number of animals per genotype used for WB  in F Statistical significance was assessed using Student's t-test in F, significance is depicted as follows: *p≤0.05, **p < 0.01, ***p< 0.001.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A, B. Representative pseudo colour images (A) and average traces (B) of sypHy  fluorescence plotted for WT and  BsnGT neurons  without treatment (black and red) and upon treatment with adenylyl cyclase activator forskolin  (gray and pink) or PKA  inhibitor H89  (light grey and orange). Data information: The scale bar is 2 µm in A",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "E. Representative immunoblot  with antibody against pSer9Syn1 and total Syn1  and total protein stain  of hippocampal  P2 fraction from WT and BsnGT mice  prepared in the presence of KN 93 to isolate PKA-dependent regulation of pSer9Syn1. F, G. Quantification of pSer9Syn1/Syn1  ratio (in F) and Syn1  (in G) on blots  from E. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers and + indicates mean. The sample size is given in brackets and corresponds to the number of analysed independent imaging experiments samples prepared from individual animals in F and G, The statistical significance was assessed in F and G using Student's t-test as is depicted in graphs as *p≤0.05, **p < 0.01, ***p< 0.001.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "H. Representative images of  hippocampal neurons from WT and  BsnGT mice  labelled with antibodies against pSer9Syn1 and total Syn1. Neurons  were pre-treated (4 µM, 1hr) with KN93 to isolate PKA-dependent phosphorylation  and then treated in addition with forskolin  or H89  before fixation. I. Quantification of staining  in H. Data information: In the plots, the interquartile range and median are depicted as boxes, minimal and maximal values as whiskers and + indicates mean. The sample size is given in brackets and corresponds to the independent visual fields obtained from 2 independent culture preparations in I. The statistical significance was assessed in I using two-way ANOVA with Tukey´s multiple comparison test as *p≤0.05, **p < 0.01, ***p< 0.001. The scale bar is 5 µm in H.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A, B. Representative pseudo colour images (A) and average traces (B) of sypHy  fluorescence plotted for untreated WT and BsnGT neurons  (black and red) and cultures treated with of 6-Bnz-cAMPS (50 µM, 1 hour; gray and pink) and rolipram  (1 µM, 30 min, light grey and orange). Data information: Scale bar is 2µm.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "I. Representative immunoblot  with antibody against CDK5-dependent pSer145PDE4B and total PDE4B  on hippocampal  tissue from WT and BsnGT animals.",
    "ncbi_link": "Bsn: 12217"
  },
  {
    "caption": "A. Immunoblotting of c-MYC and ATF4 in melanoma cells treated with NT-siRNA (-) or siASNS (#1 or #2) for 72 hr.",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Reverse transcription with quantitative PCR (RT-qPCR) of the indicated transcripts in melanoma cells 36 hr after treatment with siASNS (#1 or #2) (B)",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "C. Reverse transcription with quantitative PCR (RT-qPCR) of the indicated transcripts in melanoma cells 36 hr after treatment with siASNS, siATF4, or both (C).",
    "ncbi_link": "ASNS: 440
ATF4: 468"
  },
  {
    "caption": "D. Immunoblotting of ATF4 and ASNS in melanoma cells 72 hr after treatment with siASNS, siATF4, or both.",
    "ncbi_link": "ASNS: 440
ATF4: 468"
  },
  {
    "caption": "E. Proliferation of melanoma cells over indicated times after treatment with siASNS, siATF4, or both.",
    "ncbi_link": "ASNS: 440
ATF4: 468"
  },
  {
    "caption": "F. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS (#1 or #2).",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Immunoblotting of c-MYC in melanoma cells treated for 72 hr with siASNS, L-Asn, or both (G)",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "A. Immunoblotting of c-MYC in A375 cells treated with NT-siRNA or siASNS for 24 hr followed by cycloheximide treatment for indicated timepoints (left). Plot showing relative protein levels of c-MYC (y-axis) as a function of time lapsed (x-axis) in the left panel (right).",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with NT-siRNA (-) or siASNS (#1 or #2) (B and C)",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with siASNS, PLX-4032, or both (D).",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "F. A375 cells were treated with siASNS, SCH772984, or both for 72 hr followed by immunoblotting of phosphorylated and total GSK3-β.",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "G. A375 cells were treated with siASNS, HA-GSK3-β (S9A), or both for 72 hr followed by immunoblotting of indicated proteins.",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "H. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS, HA-GSK3-β (S9A), or both.",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "A. Immunoblotting of indicated proteins in melanoma cells treated with siASNS, sicMYC (#1 or #2), or a combination of siASNS and sicMYC (#1 or #2) for 72 hr.",
    "ncbi_link": "ASNS: 440
cMYC: 4609"
  },
  {
    "caption": "B. RT-qPCR analysis of indicated transcripts in melanoma cells 36 hr after treatment with siASNS, sicMYC, or both.",
    "ncbi_link": "ASNS: 440
cMYC: 4609"
  },
  {
    "caption": "C. Immunoblotting of indicated proteins in melanoma cells 72 hr after treatment with siASNS, sicMYC, PLX-4032, or a combination of siASNS and sicMYC, or siASNS and PLX-4032.",
    "ncbi_link": "ASNS: 440
cMYC: 4609"
  },
  {
    "caption": "D. Immunoblotting of indicated proteins in A375 cells 72 hr after treatment with siASNS, HA-GSK3-β (S9A), or both.",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "E. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, HA-GSK3-β (S9A), or both.",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "Proliferation of melanoma cells over indicated times after treatment with siASNS, sicMYC, or both (G),",
    "ncbi_link": "ASNS: 440
cMYC: 4609"
  },
  {
    "caption": "Proliferation of melanoma cells over indicated times after treatment with siASNS, HA-GSK3-β (S9A), or both (H).",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "A. Immunoblotting of indicated proteins in A375 cells 72 hr after treatment with siASNS, siSLC1A5, siSLC7A5, or a combination of siASNS and siSLC1A5, or siASNS and siSLC7A5.",
    "ncbi_link": "ASNS: 440
SLC1A5: 6510
SLC7A5: 8140"
  },
  {
    "caption": "B. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, siSLC7A5, or both.",
    "ncbi_link": "ASNS: 440
SLC7A5: 8140"
  },
  {
    "caption": "C. Proliferation of melanoma cells over indicated times after treatment with siASNS, siSLC7A5, or both.",
    "ncbi_link": "ASNS: 440
SLC7A5: 8140"
  },
  {
    "caption": "D. GC-MS-based estimation of intracellular amino acid levels in A375 cells treated with siASNS, siATF4, or both (top left); siASNS, sicMYC, or both (top right); siASNS, siSLC1A5, or both (bottom left); or siASNS, siSLC7A5, or both (bottom right). The fold change is relative to NT-siRNA-treated A375 cells.",
    "ncbi_link": "ASNS: 440
ATF4: 468
cMYC: 4609
SLC1A5: 6510
SLC7A5: 8140"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after , treatment with siASNS, sicMYC, or both",
    "ncbi_link": "ASNS: 440
cMYC: 4609"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after indicated treatment with , siASNS, siSLC7A5, or both (G)",
    "ncbi_link": "ASNS: 440
SLC7A5: 8140"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after indicated treatment with siASNS, BCH, or both (H)",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after indicated treatment with siASNS, HA-GSK3-β (S9A), or both (I)",
    "ncbi_link": "HA: 
ASNS: 440
GSK3-β: 2932"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after indicated treatment with , siASNS or indicated combinations (J)",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "Immunoblotting of indicated proteins in A375 cells 72 hr after indicated treatment with siASNS, siSLC3A2, or both (K).",
    "ncbi_link": "ASNS: 440
SLC3A2: 6520"
  },
  {
    "caption": "L. RT-qPCR analysis of indicated transcripts in melanoma cells after 36 hr treatment with siASNS, siSLC3A2, or both.",
    "ncbi_link": "ASNS: 440
SLC3A2: 6520"
  },
  {
    "caption": "M. Proliferation of melanoma cells over indicated times after treatment with siASNS, siSLC3A2, or both.",
    "ncbi_link": "ASNS: 440
SLC3A2: 6520"
  },
  {
    "caption": "E: Immunofluorescent detection and quantification of total Nanog and Esrrb protein in E14Tg2a ESCs overexpressing Nanog (left) or Esrrb (right) cultured for three days in GMEMβ/FCS/LIF. Parental E14Tg2as are shown as a reference. The red lines indicate the negative thresholds defined by staining ESCs differentiatied for 3 days in the absence of LIF and presence of retinoic acid.",
    "ncbi_link": "Esrrb: 26380
Nanog: 71950"
  },
  {
    "caption": "G: Histograms showing expression levels of Esrrb-GFP and Nanog-mCherry from the respective targeted endogenous alleles in SSEA1+ NER ESCs overexpressing Nanog (left) or Esrrb (right) cultured for three days in GMEMβ/FCS/LIF. Parental NER ESCs are shown as a reference, and wild-type E14Tg2a set the negative thresholds.",
    "ncbi_link": "Esrrb: 26380
Nanog: 71950"
  },
  {
    "caption": "H: Comparative flow cytometric analysis of Esrrb-2a-tdTomato and Nanog:GFP expression in undifferentiated SSEA-1+ TNG E-2a-tdT or Nanog-null ES∆N E-2a-tdT ESCs cultured for three days in GMEMβ/FCS/LIF. Data are shown as dot plots (top) and histogram (bottom).",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": ": Sorted SSEA-1+ and Esrrb-GFPhigh/Nanog-mCherryhigh NER ESCs were replated in GMEMβ/FCS/LIF and SSEA-1+ cells were analysed daily for Esrrb-GFP and Nanog-mCherry expression. Wild-type E14Tg2a set the negative thresholds.",
    "ncbi_link": "Esrrb: 26380
Nanog: 71950"
  },
  {
    "caption": "C: Quantitative Esrrb mRNA expression analysis of populations sorted Error bars: standard deviation of gene expression values measured in four independent experiments.",
    "ncbi_link": "Esrrb: 26380"
  },
  {
    "caption": "A: Percentage of methylated CpG dinucleotides profiled across the Esrrb and Nanog enhancer and the Nanog promoter in sorted SSEA-1+ / EsrrbHi, EsrrbMed or EsrrbNeg E-GFPd1 ESCs and TNG E-2a-tdT EpiSC. CpG methylation was assessed by measuring protection from digestion of the HpaII, AciI, Hin6I or TaqI restriction sites (indicated by vertical lines in the gene structure maps derived from the mouse reference genome (mm9) and expressed relative to the TSS in ESCs Values represent total CpG methylation levels (5mC + 5hmC). Error bars: standard deviation of the measures in four independent experiments.",
    "ncbi_link": "AciI: 
Hin6I: 
HpaII: 
TaqI: 
Esrrb: 26380
Nanog: 71950"
  },
  {
    "caption": "B: Methylated CpG dinucleotides across the Esrrb enhancer were assessed SSEA-1+ / EsrrbHi E-GFPd1 ESCs were sorted and placed back in culture overnight before resorting and methylation analysis relative to Esrrb- E-GFPd1 ESCs. Error bars: standard deviation of the measures in three independent experiments.",
    "ncbi_link": "Esrrb: 26380"
  },
  {
    "caption": "D: Quantitative ChIP-PCR analysis of OCT4, NANOG and ESRRB binding and histone modifications at the Esrrb and Nanog enhancers and the Nanog promoter in the sorted populations Error bars: standard deviation of the measures in two (NANOG, ESRRB, H3K27ac) or three (OCT4, H3K4me3, H3K4me1) independent ChIP experiments, each performed on pooled chromatin from at least three independently sorted samples. The diagrams at the bottom show the approximate position of the regions analysed for transcription factor binding or histone modifications (in color or black), along with the relative control genomic locations (grey).",
    "ncbi_link": "Esrrb: 26380
Nanog: 71950"
  },
  {
    "caption": "H, I: Binding profiles of OCT4 and NANOG in the proximity of two genes representative of (H) Class I (Tet2) or (I) Class II (Sall1) in EsrrbHi, EsrrbMed or EsrrbNeg E-GFPd1 ESCs. The relative occupancies of NANOG and OCT4 at Tet2 or Sall1 (positions highlighted by hatched boxes) alongside expression levels of Tet2 and Sall1 mRNAs in EsrrbHi (EH), EsrrbMed (EM) or EsrrbNeg (EN) GFPd1 ESCs and EpiSC (Epi) is shown at the bottom. Oct4 binding data from EpiSC",
    "ncbi_link": "Sall1: 58198
Tet2: 214133"
  },
  {
    "caption": ": Average binding profile of ESRRB, KLF4, NANOG, OCT4 and SOX2 to Class I (green), Class II (orange) or all Nanog and Oct4 bound (grey dashed line) elements in ESCs. Read counts per base pair were normalised by library size and by subtracting the background (IgG) signal.",
    "ncbi_link": "Nanog: 71950
Oct4: 18999"
  },
  {
    "caption": "(E) Representative images (Left) of smFISH in DRG section, tSNE plot of 10x Genomics (Middle), and quantitative result (Right) showed that C530044C16Rik was co-localized with Gal-Cre; Ai9 tdTomato neurons (n = 7), but not with Sst-Cre neurons (n = 6). (F) Representative smFISH images (Left), tSNE plot of 10x Genomics (Middle), and quantitative result (Right) showed that CLAP was co-localized with Sst-Cre; Ai9 tdTomato neurons (n = 6), but not with Gal-Cre neurons (n = 29). (G) Representative smFISH images (Left), tSNE plot of 10x Genomics (Middle), and quantitative result (Right) showed that Gm11549 was co-localized with Slc17a8-Cre; Ai9 tdTomato neurons (n = 5), but not with Mrgprd-Cre neurons (n = 6). (H) Representative smFISH images (Left), tSNE plot of 10x Genomics (Middle), and quantitative result (Right) showed that 2310002F09Rik was co-localized with Slc17a8-Cre; Ai9 tdTomato neurons (n = 6), but not with Slc17a8-Cre neurons (n = 6).",
    "ncbi_link": "tdTomato: 
2310002F09Rik: 100504720
CLAP: 12042
C530044C16Rik: 319981
Cre: 2777477
Gal: 855828
Mrgprd: 211578
Slc17a8: 216227
Gm11549: 100503068
Sst: 20604"
  },
  {
    "caption": "(I-K) Representative images (Right) of double smFISH showed that 2310002F09Rik was rarely co-localized with C530044C16Rik (I), CLAP (J) and Gm11549 (K). Scale bar, 10 µm.",
    "ncbi_link": "2310002F09Rik: 100504720
CLAP: 12042
C530044C16Rik: 319981
Gm11549: 100503068"
  },
  {
    "caption": "(D) Representative smFISH images in DRG sections and quantitative results showed that 2310002F09Rik and Gm14273 were more enriched in the nucleus, whereas CLAP and Gm11549 were mainly distributed in the cytoplasm. DAPI served as a nuclear marker. Scale bar, 10 μm.",
    "ncbi_link": "2310002F09Rik: 100504720
CLAP: 12042
Gm14273: 102639473
Gm11549: 100503068"
  },
  {
    "caption": "(B) Sequence conservation analysis of lincRNA CLAP and upstream mRNA Pirt in 9 different species including mouse, human, chimpanzee, rhesus monkey, rat, cow, dog, chicken and zebrafish, which were visualized with the VISTA browser. CDS, coding sequence. UTR, untranslated region.",
    "ncbi_link": "CLAP: 12042
Pirt: 193003"
  },
  {
    "caption": "(D) qPCR showed that CLAP was highly expressed in the DRG and other visceral organs such as small intestine, stomach and lung. The results are presented as mean ± SEM (n = 3). (E) qPCR showed that the expression of CLAP was gradually increased from E13.5 to adult DRGs. The results are presented as mean ± SEM (n = 3).",
    "ncbi_link": "CLAP: 12042"
  },
  {
    "caption": "(F) Representative bright-field and fluorescent images showing the Sst-cre; Ai9 neurons for calcium imaging following siCLAP transfection. Scale bar, 10 μm.",
    "ncbi_link": "CLAP: 12042
cre: 2777477
Sst: 20604"
  },
  {
    "caption": "(G) qPCR showed that the expression of CLAP was decreased by siRNA treatment in cultured Sst-Cre; Ai9 DRG neurons. The results are presented as mean ± SEM (n = 3). ** P < 0.01 versus siNC.",
    "ncbi_link": "CLAP: 12042
Cre: 2777477
Sst: 20604"
  },
  {
    "caption": "The percentage of Sst-Cre; Ai9 neurons evoked by histamine (I) was decreased by knockdown of CLAP, whereas the percentage of these neurons affected by 5-HT (J), chloroquine (K), capsaicin (L) were not changed. The results are presented as mean ± SEM (n = 4). ** P < 0.01 versus siNC.",
    "ncbi_link": "CLAP: 12042
Cre: 2777477
Sst: 20604"
  },
  {
    "caption": "(B) qPCR showed that the CLAP level was significantly decreased by siCLAP in the DRG following intrathecal injection. The results are presented as mean ± SEM (siNC = 12, siCLAP = 15). *** P < 0.001 versus siNC.",
    "ncbi_link": "CLAP: 12042"
  },
  {
    "caption": "(C-E) Knockdown of CLAP reduced itch scratching evoked by histamine (C), but not 5-HT (D) and chloroquine (E). The results are presented as mean ± SEM (For histamine and 5-HT, siNC = 12，siCLAP = 15; for chloroquine, siNC = 5，siCLAP = 8 ). ** P < 0.01 versus siNC.",
    "ncbi_link": "CLAP: 12042"
  },
  {
    "caption": "(D) The expression changes of C2-specific and itch-related genes upon CLAP knockdown by RNA-seq. Each dot represents an RNA-seq sample, and results are presented as mean ± SEM (n = 3). * P < 0.05, ** P < 0.01 and *** P < 0.001 versus siNC.",
    "ncbi_link": "CLAP: 12042"
  },
  {
    "caption": "(F) qPCR showed that downregulated CLAP and C2-specific genes including Sst, Plcb3 and Cysltr2 by siCLAP was fully rescued by overexpression of CLAPR in L4/5 DRGs of mice. The results are presented as mean ± SEM (siNC, n = 10; siCLAP, n = 6; siCLAP + CLAPR, n = 12). * P < 0.01 versus siNC and # P < 0.05, ## P < 0.01 versus the indicated treatment.",
    "ncbi_link": "CLAP: 12042
Cysltr2: 70086
Plcb3: 18797
Sst: 20604"
  },
  {
    "caption": "(I) qPCR showed that downregulated Plcb3 by siCLAP was fully rescued by knockdown of MSI2 in L4/5 DRGs of mice. The results are presented as mean ± SEM (siNC, n = 8; siCLAP, n = 6; siCLAP + siMSI2, n = 5). * P < 0.05, *** P < 0.001 versus siNC and ## P < 0.01 versus the indicated treatment.",
    "ncbi_link": "CLAP: 12042
MSI2: 76626
Plcb3: 18797"
  },
  {
    "caption": "A. Wild-type (WT), rbd2Δ or sre1Δ yeast (200 cells) containing either empty vector (EV) or a plasmid expressing sre1N (Sre1amino acids 1-440) were grown on rich medium in the presence or absence of cobalt chloride (CoCl2).",
    "ncbi_link": "rbd2: 2539469
sre1: 2540730"
  },
  {
    "caption": "B. Western blot was probed with anti-Sre1 IgG of phosphatase-treated, whole cell lysates from WT and the indicated mutants grown for the indicated time in the absence of oxygen. Dsc5 serves as a loading control and was detected by chemiluminescence. P and N denote Sre1 precursor and cleaved nuclear forms, respectively.",
    "ncbi_link": "Sre1: 2540730"
  },
  {
    "caption": "C. Indicated yeast strains expressing rbd2 or chromosomal Flag-tagged rbd2, rbd2-S130A or rbd2-H182A were analyzed for Sre1 cleavage. Western blot was performed using anti-Sre1 or anti-FlagIgG of phosphatase-treated, whole cell lysates from cells grown for 3 hr in the presence or absence of oxygen.",
    "ncbi_link": "rbd2: 2539469
Sre1: 2540730"
  },
  {
    "caption": "D. Indicated yeast strains expressing rbd2 or chromosomal Flag-tagged rbd2, rbd2-S130A or rbd2-H182A were analyzed for Sre2 cleavage by western blot probed with anti-Sre2 serum or anti-FlagIgG of phosphatase-treated, whole cell lysates from cells grown in the presence of oxygen.",
    "ncbi_link": "rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "E. Sre1 cleavage assay was performed as in (C). G128V, A127D and A186T mutant strains were obtained from our previous mutagenesis screening (Stewart et al, 2012). Dsc5 serves as a loading control.",
    "ncbi_link": "Sre1: 2540730"
  },
  {
    "caption": "G. A model substrate of Sre2 containing amino acids 423-793 (Sre2MS) with an N-terminal 3xFlag epitope tag was expressed on a plasmid under the control of a CaMV promoter in sre2Δ, dsc1Δsre2Δ or rbd2Δsre2Δ yeast strains. Whole cell lysates from indicated yeast strains were analyzed by western blot with anti-Flag antibody. Three independent isolates (A-C) are shown for each strain. Empty vector (EV) transformation serves as a negative control.",
    "ncbi_link": "dsc1: 2541251
rbd2: 2539469
sre2: 2541044"
  },
  {
    "caption": "A. Wild-type (WT) and the indicated mutant strains were grown for 3 hr at the non-permissive temperature (36°C) to inactivate Mts3. Phosphatase-treated cell lysates were analyzed by western blot with anti-Sre2 serum and imaged using chemiluminescence. P and N denote Sre2 precursor and cleaved nuclear forms, respectively.",
    "ncbi_link": "Mts3: 2540025
Sre2: 2541044"
  },
  {
    "caption": "B. WT, rbd2Δ and sre2Δ cells were treated with bortezomib (Bz) for 3 hr, and phosphatase-treated, whole cell lysates were analyzed by western blot with anti-Sre2 serum.",
    "ncbi_link": "rbd2: 2539469
sre2: 2541044"
  },
  {
    "caption": "C. WT, dsc1Δ and rbd2Δ cells carrying either empty vector (EV) or a plasmid expressing 3xFlag-Sre2MS (MS) were treated with bortezomib (Bz) for 3 hr. Whole cell lysates were analyzed by western blot with anti-Flag antibody.",
    "ncbi_link": "dsc1: 2541251
rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "E. Catalytically dead Dsc1 E3 ligase (dsc1-C634A) mutant and other indicated yeast strains were analyzed by western blot probed with anti-Sre2 serum and imaged using chemiluminescence.",
    "ncbi_link": "Dsc1: 2541251
dsc1: 2541251"
  },
  {
    "caption": "A. HumanHEK293T cells were transfected with plasmids expressing different 3xHA-tagged rhomboid proteases: S. pomberbd2, S. pomberbd2 recoded for human expression, humanRHBDL2, D. melanogaster Rho1, and P. falciparumROM4. Whole cell lysates were analyzed by western blot to detect the HA-tagged rhomboid [asterisks indicate loading control bands detected with antibody ab179726 (abcam)].",
    "ncbi_link": "rbd2: 2539469"
  },
  {
    "caption": "B. HumanHEK293T cells were transfected with plasmids expressing the indicated rhomboid substrates and either recoded S. pombe rbd2, D. melanogaster Rho1, or P. falciparumROM4. Conditioned media and cell lysates were analyzed by western blot. P and C denote precursor and cleaved products, respectively.",
    "ncbi_link": "Rho1: 36775
ROM4: 812885
rbd2: 2539469"
  },
  {
    "caption": "D. HumanHEK293T cells were transfected with plasmids expressing the indicated GFP-TatA-Flag substrates and either wild-type or mutant recoded S. pomberbd2. Whole cell lysates were analyzed by western blot.",
    "ncbi_link": "TatA: 
rbd2: 2539469"
  },
  {
    "caption": "F. HumanHEK293T cells were transfected with plasmids expressing the GFP-TatA (A8L)-Flag and recoded S. pomberbd2. C-terminal cleavage products were purified using anti-Flag antibodies and purified protein was analyzed by mass spectrometry.",
    "ncbi_link": "TatA: 
rbd2: 2539469"
  },
  {
    "caption": "B. Whole cell lysates from WT, rbd2Δ and dsc1Δ cells carrying a plasmid expressing 3xFlag-Sre2MS WT or indicated mutants were analyzed by western blot with anti-Flag antibody. P and N denote Sre2MS precursor and cleaved forms, respectively.",
    "ncbi_link": "dsc1: 2541251
rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "D-E. Whole cell lysates from WT, rbd2Δ and dsc1Δ cells carrying a plasmid expressing 3xFlag-Sre2MS WT or indicated mutants were analyzed by western blot with anti-Flag antibody. P and N denote Sre2MS precursor and cleaved forms, respectively. Asterisks indicate non-specific, loading control bands, which were used to normalize the intensities of P and N in Figure 5F. Two independent isolates, A and B, are shown for each strain.",
    "ncbi_link": "dsc1: 2541251
rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "G. The average ratio of N to P level for different Sre2MS mutants in wild-type cells (Appendix Fig S2) was plotted. Cleavage was scored as normal if the ratio was >2.",
    "ncbi_link": "Sre2: 2541044"
  },
  {
    "caption": "H. For Sre2MS mutants showing defects in cleavage, the average fold-increase in P level in dsc1Δ cells compared to WT cells from two isolates (Appendix Fig S2) was plotted. Mutants were grouped into three phenotypic classes (intermediate, dsc1Δ, and rbd2∆) according to observed precursor accumulation. Precursor accumulation was defined as dsc1Δ if <1.5 (orange), rbd2Δ if >3 (pink), and intermediate if in between (blue).",
    "ncbi_link": "dsc1: 2541251
rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "B. Recombinant proteins GST-fused Rbd2 C-terminus (Rbd2200-251), Dsc5 UBX (Dsc5323-425), Dsc2 UBA (Dsc2298-372), and GST-HA-V5 control were bound to GST magnetic beads and incubated with S. pombe cytosol fraction from wild-type cells. Equivalent amounts of unbound and bound fractions were probed for anti-Cdc48, anti-ubiquitin and anti-GSTIgG.",
    "ncbi_link": "Dsc2: 2542884"
  },
  {
    "caption": "C. GSTpulldown assay was performed as in (B) using truncated forms of Rbd2 C-terminus; Rbd2200-251, Rbd2200-225, Rbd2225-251 and Rbd2200-240. Unbound (1x) and bound (5x) fractions were analyzed by western blotting",
    "ncbi_link": "Rbd2: 2539469"
  },
  {
    "caption": "A. Detergent-solubilized yeast extracts from cells containing chromosomal Flag-tagged rbd2 or rbd2-G246R in rbd2Δ background were prepared, and proteins associated with Rbd2-Flag were immunopurified using anti-Flag magnetic beads. Equal amount of total (lanes 1-3) along with 25x bound fractions (lanes 4-6) were analyzed by western blot with anti-Cdc48 serum and anti-FlagIgG.",
    "ncbi_link": "rbd2: 2539469"
  },
  {
    "caption": "C. Biotin-phenol labeling was performed for 1 min with H2O2 treatment as described in Materials and Methods. WT cells or rbd2Δ cells carrying rbd2-Flag-APEX2 (rbd2-F-AX) or rbd2-G246R-Flag-APEX2 (G246R-F-AX) plasmid were lysed after biotin-labeling reaction, and proteins were denatured by heating the cells in lysis buffer containing 1%SDS. Biotinylated proteins were then enriched using streptavidin magnetic beads. Lysates and 50x-enriched eluates were analyzed by western blot with IRDye 800CW Streptavidin, anti-Cdc48 serum, or anti-FlagIgG.",
    "ncbi_link": "APEX2: 606508
rbd2: 2539469"
  },
  {
    "caption": "A. Yeast strains (200 cells) containing chromosomal Flag-tagged rbd2, rbd2-G244R, rbd2-G246R or rbd2-S130A in rbd2Δ background and sre1Δ yeast were grown on rich medium in the absence or presence of cobalt chloride (CoCl2).",
    "ncbi_link": "rbd2: 2539469
sre1: 2540730"
  },
  {
    "caption": "B. Western blot of phosphatase-treated, whole cell lysates from strains in (A) grown for 3 hr in the presence or absence of oxygen was probed with anti-Sre1 or anti-Flag IgG. P and N denote Sre1 precursor and cleaved nuclear forms, respectively.",
    "ncbi_link": "Sre1: 2540730"
  },
  {
    "caption": "C. Sre2 cleavage was assayed by western blot using anti-Sre2 serum or anti-Flag IgG of phosphatase-treated, whole cell lysates from the indicated strains. N denotes Sre2 cleaved nuclear form.",
    "ncbi_link": "Sre2: 2541044"
  },
  {
    "caption": "D. Whole cell lysates from indicated yeast strains carrying a plasmid expressing 3xFlag-Sre2MS were analyzed by western blot with anti-Flag antibody. Two independent isolates, A and B, are shown for each strain. Asterisk denotes non-specific band.",
    "ncbi_link": "Sre2: 2541044"
  },
  {
    "caption": "F. Yeast strains containing Flag-tagged rbd2-SHP, rbd2-SHP*, rbd2-G246R-SHP, and rbd2-G246R-SHP* were generated in rbd2Δ background by chromosomal integration of the rbd2 fusion proteins depicted in (E). Indicated yeast strains were then assayed for Sre1 cleavage as in (B).",
    "ncbi_link": "rbd2: 2539469"
  },
  {
    "caption": "H. Wild-type, sre2Δ or strains containing chromosomal Flag-tagged rbd2, rbd2-G246R or rbd2-S130S in rbd2Δ background (lane 7-12) were treated with bortezomib (Bz) for 2 hr, and phosphatase-treated, whole cell lysates were analyzed by western blot with anti-Sre2 serum or anti-Flag IgG.",
    "ncbi_link": "rbd2: 2539469
sre2: 2541044"
  },
  {
    "caption": "A. Western blot of phosphatase-treated whole cell lysates from yeast strains carrying rbd2-Flag-APEX2 (rbd2-F), rbd2-G246R-Flag-APEX2 (G246R) or rbd2-S130A-Flag-APEX2 (S130A) plasmid in rbd2Δ background and sre1Δ yeast was probed with anti-Sre1 or anti-Flag IgG. P and N denote Sre1 precursor and cleaved nuclear forms, respectively.",
    "ncbi_link": "APEX2: 606508
rbd2: 2539469
sre1: 2540730
Sre1: 2540730"
  },
  {
    "caption": "B. Indicated yeast strains (200 cells) containing chromosomal Flag-tagged rbd2, rbd2-G246R or rbd2-S130A in rbd2Δ background (lane 3-5) or yeast strains (200 cells) carrying rbd2-Flag-APEX2, rbd2-G246R-Flag-APEX2 or rbd2-S130A-Flag-APEX2 plasmid in rbd2Δ background (lane 6-8) were grown on rich medium in the absence or presence of cobalt chloride (CoCl2).",
    "ncbi_link": "APEX2: 606508
rbd2: 2539469"
  },
  {
    "caption": "C. Comparison of Rbd2 protein levels from overexpression system to endogenous expression. Western blot of whole cell lysates from yeast strains containing chromosomal Flag-tagged rbd2, rbd2-G246R or rbd2-S130A in rbd2Δ background and yeast strains carrying rbd2-Flag-APEX2, rbd2-G246R-Flag-APEX2 or rbd2-S130A-Flag-APEX2 plasmid in rbd2Δ background was probed with anti-FlagIgG. For quantification, the intensity of Flag band in each lane was normalized to the non-specific band (asterisk).",
    "ncbi_link": "APEX2: 606508
rbd2: 2539469"
  },
  {
    "caption": "D. rbd2Δ cells expressing indicated plasmids of GFP-Anp1 or GFP-Sre2MS together with rbd2-Flag-APEX2, rbd2-S130A-Flag-APEX2 or rbd2-S130A/G246R-Flag-APEX2 were treated with Bz at a concentration of 1 mM for 2 hr prior to biotin-labeling reaction. After labeling termination, cells were lysed and denatured as described in Materials and Methods. Biotinylated proteins were then enriched using streptavidin magnetic beads. Lysates (1x input) and 100x-enriched eluates were analyzed by western blot with IRDye 800CW Streptavidin, anti-Flag IgG, anti-Cdc48 serum, and anti-GFP IgG. Intensity of GFP band in enriched sample was normalized to that in the corresponding input sample, then normalized to the Flag intensity in enriched sample. Relative intensities of biotinylated GFP level are shown in bar graph. Error bars denote standard deviation from three biological replicates.",
    "ncbi_link": "Anp1: 2539685
APEX2: 606508
rbd2: 2539469
Sre2: 2541044"
  },
  {
    "caption": "(A) Graph showing the relative expression of Drosha in FAPs after Drosha down-regulation by siRNA (n=4, biological replicates). Values correspond to the average ± SEM. Star (*) indicates statistical analysis by t-test relative to FAPs TSA treated and transfected with scramble (Scr); **p<0.01.",
    "ncbi_link": "Drosha: 14000"
  },
  {
    "caption": "(B) Representative images of myogenic differentiation of MuSCs assessed by immunostaining for MyHC (green). MuSCs were cultured alone (-) or in transwell co-culture with FAPs isolated from mdx mice treated either with vehicle (+FAPs CTR) or TSA (0.6 mg/kg/day for 15 days by i.p.) (+FAPs TSA), and transfected with scramble (Scr siRNA) or Drosha siRNA (Drosha siRNA) prior to co-culture with MuSCs. Scale bar = 50 μm. (C) Graph showing the fusion index of MuSCs in the conditions described in (B) (n=4, biological replicates). Values correspond to the average ± SEM. Star (*) indicates statistical analysis by Tukey test relative to MuSCs alone (-); *p<0.05, ****p<0.0001. Hash (#) indicates statistical analysis by Tukey test relative to MuSCs in co-culture with FAPs CTR transfected with scramble (Scr); ##p < 0.01. Cross (†) means Tukey analysis compared to MuSCs in co-culture with FAPs TSA transfected with scramble (Scr): ††††p < 0,0001. § represents statistical analysis by 2way Anova test. §§§p < 0,001.",
    "ncbi_link": "Drosha: 14000"
  },
  {
    "caption": "(E) Representative images of miR-206-3p (violet) immunohistochemistry in vastus medialis bioptic samples of Control and DMD patients at different ages: 1 year (n=2), 4 years (n=3) and 9 years old (n=2). (F) Graph representing miR-206-3p violet area quantification relative to (E). ",
    "ncbi_link": "miR-206-3p: 406989"
  },
  {
    "caption": "(A) Representative images of Sca-1 (green), Laminin (white), DAPI (blue) immunofluorescence, and miR-206-3p (violet) immunohistochemistry on 10 uM sequencial cryosections of Tibialis Anterior (TA) of young mdx mice (CTR) and after TSA treatment (TSA) (0.6 mg/kg/day for 15 days by i.p.) (n=6). Scale bar = 25 μm. (B) Graph showing the quantifications of miR-206-3p violet area relative to conditions indicated in (A). Star (*) indicates t-test analysis **p<0.01. Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "miR-206-3p: 387202"
  },
  {
    "caption": "(C) Graph representing the miR-206-3p relative expression in EVs isolated from muscle interstitium of tibialis anterior from wild type mice (CTR), mdx young and old mice (control -CTR- and TSA treated) (n=4). Star (*) indicates Tukey analysis compared to wild type mice (CTR), ****p < 0.0001; hash (#) indicates Tukey analysis compared to mdx young CTR, #### p<0.0001. § represents statistical analysis by Anova test. §§§§ p<0,0001.",
    "ncbi_link": "miR-206-3p: 387202"
  },
  {
    "caption": "(D) Representative images of CD90 (green), Dapi (blue) and miR-206-3p (violet) immunohistochemistry in brachial biceps bioptic samples of DMD patient before (CTR) and after Givinostat treatment (GIV). Scale bar = 50 μm. (E) Graph showing the quantifications of miR-206-3p violet area measured as pixel^2/field relative to the experimental points indicated in (D) (n=18, biological replicates). Star (*) indicates t-test analysis. **p<0.01. Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "miR-206-3p: 406989"
  },
  {
    "caption": "(F) Graph showing the relative expression of miR-206-3p in EVs isolated from a human population of muscle resident cells enriched in FAPs (ehFAPs) isolated from biopsies of two DMD patients (DMD-1 and DMD-2) before (CTR) and after (GIV) Givinostat treatment, Two technical replicates are shown.",
    "ncbi_link": "miR-206-3p: 406989"
  },
  {
    "caption": "(C) Graph showing the relative expression of miR-206-3p in MuSCs isolated as described in (A and B) and in MuSCs from muscles injected with PKH67-labeled EVs isolated from FAPs of 1.5 month old mdx mice exposed to TSA, and then transfected or not with Drosha siRNA (siRNA Drosha) (n=4). Star (*) means significance relative to MuSCs that not uptake PKH67-labled EVs, **p < 0.01. Hash (#) means significance compared to MuSCs that uptake EVs-FAPs TSA, ##p < 0.01. § indicates Anova analysis, §§p<0,01.",
    "ncbi_link": "Drosha: 14000
miR-206-3p: 387202"
  },
  {
    "caption": "(D) Graph showing the expression levels of miR-206-3p and miR-145-5p in FAPs treated or not with TSA after antagomiR treatment (n=3, biological replicates). Star (*) indicates statistical analysis by t-test relative to FAPs -; *p<0.05, **p<0.01",
    "ncbi_link": "miR-145-5p: 387163
miR-206-3p: 387202"
  },
  {
    "caption": "(E) Graph showing the expression levels of miR-206-3p and miR-145-5p in FAPs-derived EVs treated or not with TSA after antagomiR treatment (n=3, biological replicates). Star (*) indicates statistical analysis by t-test relative to FAPs -; *p<0.05.",
    "ncbi_link": "miR-145-5p: 387163
miR-206-3p: 387202"
  },
  {
    "caption": "Stainings and relative measurements on Tibialis Anterior muscle transversal sections of 1.5 months old mdx mice treated daily for 21 days with intra-peritoneal injection of vehicle (CTR) or TSA, or once a week with intramuscular injections (Tibialis Anterior) of EVs derived from FAPs (EVs-FAPs) exposed or not to TSA in vivo (EVs-FAPs CTR -, EVs-FAPs TSA -) EVs derived from FAPs control transfected with the antagomiR-206 (EVs-FAPs CTR A-206) and of EVs-FAPs TSA transfected with antagomiR-206 and antagomiR-145 (EVs-FAPs TSA A-206, EVs-FAPs TSA A-145). EVs were injected every seven days and sacrificed after 21 days of treatment (n=5 for CTR, TSA EVs-FAPs CTR and EVs-FAPs TSA while for AntagomiRs n=3, biological replicates). (F) Representative images of immunofluorescence for embryonic myosin heavy chain (eMyHC-red) and laminin (Lam-cyan) stainings. Scale bar = 50 μm. (G) Graph showing the quantification of cross-sectional area (CSA). (H) Graph showing the quantification of muscle regeneration (eMyHC). Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "miR-145: 387163
miR-206: 387202"
  },
  {
    "caption": "Stainings and relative measurements on Tibialis Anterior muscle transversal sections of 1.5 months old mdx mice treated daily for 21 days with intra-peritoneal injection of vehicle (CTR) or TSA, or once a week with intramuscular injections (Tibialis Anterior) of EVs derived from FAPs (EVs-FAPs) exposed or not to TSA in vivo (EVs-FAPs CTR -, EVs-FAPs TSA -) EVs derived from FAPs control transfected with the antagomiR-206 (EVs-FAPs CTR A-206) and of EVs-FAPs TSA transfected with antagomiR-206 and antagomiR-145 (EVs-FAPs TSA A-206, EVs-FAPs TSA A-145). EVs were injected every seven days and sacrificed after 21 days of treatment (n=5 for CTR, TSA EVs-FAPs CTR and EVs-FAPs TSA while for AntagomiRs n=3, biological replicates). (I) Representative images of Masson's Trichrome staining. Scale bar = 50 μm. (J) Graph showing the quantifications of muscle fiber area fraction (MFAF). (K) Graph showing the quantifications of fibrotic area. Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "miR-145: 387163
miR-206: 387202"
  },
  {
    "caption": "Stainings and relative measurements on Tibialis Anterior muscle transversal sections of 1.5 months old mdx mice treated daily for 21 days with intra-peritoneal injection of vehicle (CTR) or TSA, or once a week with intramuscular injections (Tibialis Anterior) of EVs derived from FAPs (EVs-FAPs) exposed or not to TSA in vivo (EVs-FAPs CTR -, EVs-FAPs TSA -) EVs derived from FAPs control transfected with the antagomiR-206 (EVs-FAPs CTR A-206) and of EVs-FAPs TSA transfected with antagomiR-206 and antagomiR-145 (EVs-FAPs TSA A-206, EVs-FAPs TSA A-145). EVs were injected every seven days and sacrificed after 21 days of treatment (n=5 for CTR, TSA EVs-FAPs CTR and EVs-FAPs TSA while for AntagomiRs n=3, biological replicates). (L) Representative images of myeloperoxidase staining (MPO-red). Scale bar = 50 μm. (M) Graph showing the quantifications of inflammation (MPO). Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "miR-145: 387163
miR-206: 387202"
  },
  {
    "caption": "A) Representative images of myogenic differentiation of MuSCs assessed by immunostaining for MyHC (green). Nuclei were counterstained with DAPI (blue). MuSCs were cultured alone (-) or with EVs (EVs FAPs) isolated from FAPs in vivo exposed or not to TSA (CTR and TSA) and transfected or not with Antagomir-206 (- and A-206). (n=7 for all samples, but antagomir's samples n=3, biological replicates). Scale bar =50 μm. (B) Graph showing the fusion index of MuSCs in the condition described in (A). Star (*) indicates statistical analysis by Tukey test relative to MuSCs cultured alone (-), *p < 0.05, ****p>0,0001; hash (#) means significance compared to EVs-FAPs CTR -, ###p<0,001; and (†) means significance to EV-FAPs TSA -, †††† p<0,0001. § indicates significance by Anova test; §§§§ p>0,0001.",
    "ncbi_link": "mir-206: 387202"
  },
  {
    "caption": "(C) Graph relative to Notch3 expression in MuSCs isolated from 1.5 month old mdx mice treated either with vehicle (CTR) or TSA (TSA), and in EVs derived from FAPs (EVs-FAPs) isolated from 1.5 month old mdx mice treated either with vehicle (CTR) or TSA (TSA) (n=3). Star (*) indicates statistical analysis by Tukey test relative to mdx vehicle treated mdx mice (CTR); *p<0,05;. hash (#) means significance compared to EVs-FAPs CTR, ##p<0,01. § indicates significance by Anova test; §§ p>0,01.",
    "ncbi_link": "Notch3: 18131"
  },
  {
    "caption": "(D) Graph relative to Notch1 expression in MuSCs isolated from 1.5 month old mdx mice treated either with vehicle (CTR) or TSA (TSA), and in EVs derived from FAPs (EVs-FAPs) isolated from 1.5 month old mdx mice treated either with vehicle (CTR) or TSA (TSA) n=3. Star (*) indicates statistical analysis by Tukey test relative to mdx vehicle treated mdx mice (CTR); *p<0,05;. hash (#) means significance compared to EVs-FAPs CTR; *p < 0.05. § indicates significance by Anova test; §§ p>0,01.",
    "ncbi_link": "Notch1: 18128"
  },
  {
    "caption": "(F) From left to right: representative images of myofibers cultured for 24 hours alone (-) or with conditioned media of FAPs that were previously exposed or not to TSA and GW4869 (MEDIA-FAPs) or extracellular vesicles (EVs-FAPs) collected from FAPs exposed or not to TSA in vivo (CTR and TSA) and transfected with antagomiR-206 (TSA A-206). Myofibers have been stained for EdU(Cyan), immunofluorescence with Pax7 (green), MyoD (red). Nuclei were counterstained with DAPI (blue). (n=3). Scale bar = 25 μm. (G) Graph showing the average of nuclei positive for Pax7 (green), MyoD (red) in the conditions indicated in (F). Star (*) indicates statistical analysis by Tukey test relative to myofibers cultured alone (-), (n=3, biological replicates). *p<0,05, **p< 0.01; ***p<0,001; ***p<0,0001; hash (#) means significance compared to MEDIA FAPs CTR, #p<0,05; (†) means significance to EV-FAPs CTR, † p<0,05; while ¶ means significance compare to EVs-FAPs TSA, ¶¶¶¶ p<0,0001. § means significance by Anova test; §§ p < 0.01.",
    "ncbi_link": "miR-206: 387202"
  },
  {
    "caption": "The expression of Il1b was measured in whole brain using quantitative PCR 1 hour, 2 hours and 6 hours after I.P. challenge (n=6 mice per group). Data are expressed as mean ± STDEV and were tested by two-way ANOVA with Bonferroni's post-test; *P<0.05, **P<0.01, ***P<0.001. Symbols above bars are versus PBS at the relevant time-point.",
    "ncbi_link": "Il1b: 16176"
  },
  {
    "caption": "WT (E-G) and Nlrp3-/- (H-J) mixed glia were primed with MPSIIIA GAG or LPS. ATP (5 mM), cholesterol crystals (1 mg/ml) or amyloid-β fibrils (Aβ1-40 4.3 μM and Aβ1-42 5 μM) were added 4 hours post-priming stimulus, and the secretion of IL-1β into the media measured via ELISA after a further 20 hours (n=3 independent experiments each with 3 inter-experimental replicates). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; *P<0.05, ***P<0.001",
    "ncbi_link": "Nlrp3: 216799"
  },
  {
    "caption": "The biological activity of LV-mediated IL-1Ra was assessed in vitro. RAW264.7 macrophages were transduced with LV.IL1RN or LV.GFP vectors at a MOI of 10. After 72 hours cells were stimulated with recombinant hIL-1β and the expression of TNF-α assessed after a further 48 hours. (n=3 independent experiments each with 3 inter-experimental replicates). Data are expressed as mean ± STDEV and were tested by two-way ANOVA with Bonferroni's post-test; *P<0.05, **P<0.01, ***P<0.001. Symbols above bars are versus NTC within a treatment group.",
    "ncbi_link": "GFP: 
IL-1Ra: 3557
IL1RN: 3557"
  },
  {
    "caption": "Human IL-1Ra expression was quantified in the plasma of mice at 6 months of age (4 months post-transplant) (n=10 mice per group). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; WT vs. LV.IL1RN P<0.0001; MPSIIIA vs. LV.IL1RN P<0.0001. Symbols above bars are versus WT.",
    "ncbi_link": "IL1RN: 3557"
  },
  {
    "caption": "Quantification of human IL-1Ra levels in the brain of transplanted MPSIIIA mice (n=10 mice per group). Data are expressed as mean ± STDEV and were tested by one-way ANOVA with Tukey's post-test; WT vs. LV.IL1RN P<0.0001; MPSIIIA vs. LV.IL1RN P<0.0001. Symbols above bars are versus WT.",
    "ncbi_link": "IL1RN: 3557"
  },
  {
    "caption": "Representative sections from 6-month old MPSIIIA and LV.IL1RN transplanted MPSIIIA mice. Sections show the CA3 region of the hippocampus. Cells expressing high levels of human IL-1Ra are indicated with black arrows. 40x, scale bar, 50 μm (n=4 mice per group).",
    "ncbi_link": "IL1RN: 3557"
  },
  {
    "caption": "(B) Immunoblot  of WT, cGAS  KO, and MAVS  KO THP1 cells Data information: Panel (B) is representative of two independent biological experiments.",
    "ncbi_link": "cGAS: 115004
MAVS: 57506"
  },
  {
    "caption": "(D)  RT-qPCR analysis of VZV ORF63  (immediate early (IE) gene), ORF54  (early (E) gene), and ORF40  (late (L) gene) transcripts in cells infected as in (C). Graphs show expression relative to GAPDH. Data information: Panel (D) show pooled data from three repeats, where each data point represents an independent biological experiment (n=3 ± SEM). Statistical analysis in panels (D), was paired t-tests hpi: hours post infection",
    "ncbi_link": "GAPDH: 
ORF40: 1487708
ORF54: 1487723
ORF63: 1487711"
  },
  {
    "caption": "(E) RT-qPCR analysis of IFNB1, IFI44, and IFIT1  expression in cells infected as in (C). Graphs show expression relative to GAPDH. Data information: Panel (E) show pooled data from three repeats, where each data point represents an independent biological experiment (n=3 ± SEM). Statistical analysis in panel (E) paired ratio t-tests. hpi: hours post infection",
    "ncbi_link": "GAPDH: 2597
IFI44: 10561
IFIT1: 3434
IFNB1: 3456"
  },
  {
    "caption": "(F) Activity of  Lucia luciferase (secreted under an IRF3-dependent promotor) was determined in supernatants of cells infected as in (C) by  QUANTI-Luc assay. Data information: Panel , (F), show pooled data from four repeats, where each data point represents an independent biological experiment (n=4 ± SEM). Statistical analysis in panels (F), was paired t-tests hpi: hours post infection, WT: wild type, KO: knockout.",
    "ncbi_link": "Lucia luciferase: 
IRF3: 3661"
  },
  {
    "caption": "(A) HEK293T  cells were transfected with pRL-TK, p125-F-Luc, expression plasmids for human cGAS  and human STING, as well as expression plasmids for individual ORFs. The next day luciferase activity  was determined. For each ORF a z-value was calculated and ORFs sorted by descending values. (B) The experiment shown in panel (A) was repeated three times and for each ORF in each experiment a rank was determined according to z-value (highest z-value = rank 1). Ranks are displayed as a heatmap. The first row shows results displayed in panel (A). Data information: Panel (A) is representative of three independent biological experiments, where each data point represents a technical replicate (mean ± SD). The three independent experiments are summarised in panel (B), where the data from (A) forms the first row.",
    "ncbi_link": "F-Luc: 
cGAS: 115004
STING: 340061
TK: 24271467"
  },
  {
    "caption": "(C) HEK293T  cells were transfected as in (A,B) with expression constructs for VZV ORF9  or empty vector. In parallel, reporter expression was stimulated by co-transfection of the RIG-I-CARD plasmid instead of hcGAS  and hSTING. Data information Panel (C) is representing two independent biological experiments, where each data point represents a technical replicate (mean ± SD).",
    "ncbi_link": "cGAS: 115004
RIG-I: 23586
ORF9: 1487674
STING: 340061"
  },
  {
    "caption": "(D) Western blot  analysis of PMA-differentiated THP1 monocytes  stably transduced with either V5-tagged VZV ORF9  or GFP  using the indicated antibodies. Data information: Panels (D) are representing two independent biological experiments. In (E) each data point represents a technical replicate.",
    "ncbi_link": "GFP: 
V5: 
ORF9: 1487674"
  },
  {
    "caption": "(E) THP1 monocytes  stably transduced with either VZV ORF9  or GFP were PMA-differentiated and transfected with indicated doses of dsDNA. Expression of IFNB1  and IFNL1  was assessed by RT-qPCR. Graphs show expression relative to GAPDH. Data information: Panels (E) are representing two independent biological experiments. In (E) each data point represents a technical replicate.",
    "ncbi_link": "GFP: 
GAPDH: 2597
IFNB1: 3456
IFNL1: 282618
ORF9: 1487674"
  },
  {
    "caption": "(F) THP1 monocytes  stably transduced with either VZV ORF9  or GFP  were treated with the STING  agonist diABZi  (0.005 μM). Expression of IFNB1, IFIT1  and IFI44  was assessed by RT-qPCR. Graphs show expression relative to GAPDH. Data information: Panel (F) shows pooled data from three and two repeats, respectively, where each data point represents an independent biological experiment (horizontal bars show means). Statistical analysis in (F) were paired t-tests.",
    "ncbi_link": "GFP: 
GAPDH: 2597
IFI44: 10561
IFIT1: 3434
IFNB1: 3456
ORF9: 1487674"
  },
  {
    "caption": "(I) PMA-differentiated THP1  cells were co-cultured with VZV-ORF9ecDHFR-infected MeWo  cells for 1h in the presence of TMP, washed, and incubated for another 24h in the presence of TMP. Cells were then washed extensively and fresh medium was added that was supplemented or not with TMP. Expression levels of IFNB1, IFIT1, and IFI44  were measured by  RT-qPCR after a further 24h incubation. Graphs show expression relative to GAPDH. Mean fold changes are indicated. Data information: Panel (I) shows pooled data from three repeats, where each data point represents an independent biological experiment. Statistical analysis in (I) were paired t-tests.",
    "ncbi_link": "DHFR: 944790
GAPDH: 2597
IFI44: 10561
IFIT1: 3434
IFNB1: 3456
ORF9: 1487674"
  },
  {
    "caption": "(B) THP1 monocytes  stably transduced with either VZV FLAG-ORF9  or FLAG-GFP  were PMA-differentiated overnight. The next day, cells were lysed and ectopically expressed proteins were immunoprecipitated  using α-FLAG  antibody. Input, unbound and IP  fractions were subjected to immunoblotting  using the indicated antibodies. Data information: Panels (B), are representative of three independent experiments.",
    "ncbi_link": "FLAG: 
GFP: 
ORF9: 1487674"
  },
  {
    "caption": "(C) HaCaT  cells and PMA-differentiated THP1  cells were infected with WT VZV  or VZVORF9-V5 through co-culture with infected MeWo  cells for 48 hours. Cells were lysed and ORF9  was immunoprecipitated  using α-V5 antibody. Input and IP  fractions were subjected to immunoblotting  using the indicated antibodies. Data information: Panel (C) is representative of two (HaCaT) and three (THP1) independent experiments.",
    "ncbi_link": "V5: 
ORF9: 1487674"
  },
  {
    "caption": "(D) HEK293T  cells were seeded onto glass coverslips and were transfected with human cGAS-V5, FLAG-ORF9, or both together. The next day, cells were fixed, permeabilised and stained  using α-V5-FITC, rabbit-α-FLAG, and goat-α-rabbit-AF647  antibodies, and DAPI. Mounted coverslips were imaged using  confocal microscopy. Scale bars: 15 µm. Data information: Panels (D), are representative of three independent experiments.",
    "ncbi_link": "FLAG: 
V5: 
cGAS: 115004
ORF9: 1487674"
  },
  {
    "caption": "(B) HEK293T  cells were transfected with expression plasmids for human cGAS   and ORF9  truncation mutants. The next day cells were lysed and ORF9  proteins were immunoprecipitated  using α-FLAG  antibody. IP  fractions were subjected to immunoblotting  using the indicated antibodies. Data information: Results shown in panels (B) are representative of two independent experiments.",
    "ncbi_link": "ORF9: 1487674"
  },
  {
    "caption": "(E) HEK293T  cells were transfected with expression plasmids for FLAG-GFP  or FLAG-ORF9. The next day cells were lysed, and the lysate was spiked with biotinylated VACV70mer dsDNA. DNA  was precipitated using streptavidin  beads and fractions were subjected to immunoblotting  using the indicated antibodies. Data information: Results shown are representative of two independent experiments.",
    "ncbi_link": "FLAG: 
GFP: 
ORF9: 1487674"
  },
  {
    "caption": "(C) HEK293T  cells were transfected with expression plasmids for FLAG-GFP  or FLAG-ORF9  as indicated. The next day cells were lysed, and the lysate was spiked with biotinylated VACV70mer dsDNA. DNA  was precipitated using streptavidin  beads and proteins were analysed by immunoblotting  using the indicated antibodies. Data information: Data shown in panels (C) are representative of two independent experiments.",
    "ncbi_link": "FLAG: 
GFP: 
ORF9: 1487674"
  },
  {
    "caption": "(D) HEK293T  cells were transfected with expression plasmids for human cGAS  and FLAG-GFP  or FLAG-ORF9. The next day cells were lysed, and proteins were immunoprecipitated  using α-FLAG  antibody and analysed by immunoblotting  using the indicated antibodies. Data information: Data shown in panels (D) are representative of two independent experiments.",
    "ncbi_link": "FLAG: 
GFP: 
ORF9: 1487674"
  },
  {
    "caption": "(E) THP1  cells stably transduced with GFP, ORF9, or ORF9-DM were transfected with the indicated amounts of E.coli dsDNA. The next day, IFNB1  expression was assessed by RT-qPCR. Data information: Panel (E) shows pooled data from two repeats, where each data point represents an independent biological experiment (n=2 +/- range).",
    "ncbi_link": "GFP: 
IFNB1: 3456
ORF9: 1487674"
  },
  {
    "caption": "(D) ATG5 and ATG7 mRNA levels in indicated tissues (n=4)",
    "ncbi_link": "ATG5: 11793
ATG7: 74244"
  },
  {
    "caption": "(J) Adβ3 mRNA in eWAT from 10‐mo‐old RD‐fed Con and KO mice (n=4), and in (K) inguinal (ingWAT) from 4‐mo‐oldcold‐challenged RD‐fed Con and KO mice (n=3).",
    "ncbi_link": "Adβ3: 11556"
  },
  {
    "caption": "(A,B) Tmem26 and tbx1 mRNA levels in epididymal eWAT, and (C,D) ingWAT from Atg7Flox/Floxmice (4 months (mo)) injected in BAT with empty (Con AdV) or Cre‐expressing (Cre AdV) adenoviruses and cold‐exposed or not (basal) for 75 min (n=4-5).",
    "ncbi_link": "Cre: 
Atg7: 74244
tbx1: 21380
Tmem26: 327766"
  },
  {
    "caption": "(E,F) hematoxylin and eosin (HE)‐stained ingWAT section from Atg7Flox/Flox mice (4 months (mo)) injected in BAT with empty (Con AdV) or Cre‐expressing (Cre AdV) adenoviruses and cold‐exposed or not (basal) for 75 min (n=4-5).",
    "ncbi_link": "Cre: 
Atg7: 74244"
  },
  {
    "caption": "(H) Expression of MuRF‐1 and Atrogin‐1 in GA and TA from 10‐mo‐old Con and KO mice (n=4)",
    "ncbi_link": "Atrogin‐1: 67731
MuRF‐1: 433766"
  },
  {
    "caption": "(K) mRNA for IRS1, (L) IRS2 in epididymal white adipose tissue (eWAT) and GA from 10‐mo‐old Con and KO mice (n=6).",
    "ncbi_link": "IRS1: 16367
IRS2: 16368"
  },
  {
    "caption": "Fold enrichment of γH2AX at telomere repeats by real-time PCR. Graph represents fold enrichment of γH2AX at telomeric repeats between IgG control, 3 and 30 month old whole mouse hearts. Data are mean ± SEM of n=3 mice per age group.",
    "ncbi_link": "γH2AX: 15270"
  },
  {
    "caption": "% of telomere FISH signal loss in 30 months old wild-type mice and late generation Terc-/- mice (6 months old) in comparison to 4 months old wild-type mice. Data are from n=3 mice. >100 CMs were analysed per mouse.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Representative images of rat neonatal CMs 4 days following transfection with a FLAG-tagged TRF1-FokI-D450A (top row) or TRF1-FokI (middle and bottom row) fusion protein (cell treatments the same for all subsequent panels in Figure) (red - telo-FISH; green - γH2A.X). Images are z-projections of 0.1µm stacks taken with 100X objective. White arrows indicate co-localisation between telomeres and γH2A.X, with co-localising foci amplified in the right panels (taken from single z-planes where co-localisation was found). Scale bar represents 3.5μm. Scale bar in magnified images showing individual co-localisation 500nm.",
    "ncbi_link": "FLAG: 
FokI: 
TRF1: "
  },
  {
    "caption": "% of γH2A.X foci co-localising with telomeres (B) in FLAG-tagged TRF1-FokI-D450A- and TRF1-FokI-expressing CMs. Data are mean ± SEM of n=4 independent experiments. >50 cells were analysed per condition. Statistical analysis was performed by two-tailed t-test ***P<0.001.",
    "ncbi_link": "FLAG: 
FokI: 
TRF1: "
  },
  {
    "caption": "mean number of Telomere-associated Foci (TAF) (C) in FLAG-tagged TRF1-FokI-D450A- and TRF1-FokI-expressing CMs. Data are mean ± SEM of n=4 independent experiments. >50 cells were analysed per condition. Statistical analysis was performed by two-tailed t-test ***P<0.001.",
    "ncbi_link": "FLAG: 
FokI: 
TRF1: "
  },
  {
    "caption": "Mean % of FLAG-labelled CMs positive for SA-β-Gal activity. Data are mean ± SEM of n=3 independent experiments. >100 cells were quantified per condition. Statistical analysis performed using two tailed t test; **P<0.01.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "Expression of p21 mRNA (as a function of β-actin and Gapdh) by real-time PCR in TRF1-FokI-D450A and TRF1-FokI expressing CMs. Data are mean ± SEM of n=6 independent experiments. Statistical analysis performed using two tailed t test; ***P<0.001.",
    "ncbi_link": "FokI: 
Gapdh: 
TRF1: 
β-actin: 
p21: 114851"
  },
  {
    "caption": "Mean± SEM cell surface area (μm2) of FLAG-labelled CMs expressing TRF1-FokI-D450A and TRF1-FokI. Statistical analysis performed using two tailed t test; ***P<0.001. Scale bar represents 50μm.",
    "ncbi_link": "FLAG: 
FokI: 
TRF1: "
  },
  {
    "caption": "(Above) RNA-sequencing of purified CMs from 4 mice per age group reveal age-dependent increased expression of 3 secreted proteins Edn3, Tgfb2, and Gdf15; the colour intensity represents column Z-score, where red indicates highly and blue lowly expressed. (Below) mRNA expression of Edn3, Tgfb2, and Gdf15 was independently validated by RT-PCR in young and old isolated adult CMs. Data are mean ±S.E.M of n=8 mice per group.",
    "ncbi_link": "Edn3: 13616
Gdf15: 23886
Tgfb2: 21808"
  },
  {
    "caption": "Real-time PCR gene expression analysis of MAO-A, MnSOD and catalase in isolated mouse CMs from young (3 months) and old (20 months) mice.",
    "ncbi_link": "catalase: 12359
MAO-A: 17161
MnSOD: 20656"
  },
  {
    "caption": "Mean % of TAF-positive nuclei (left graphs) or mean % of TAF (right graphs) in wild-type (control) compared to MAO-A transgenic mice with or without drinking water supplemented with 1.5g/kg/day NAC from the age of 4 to 24 weeks Data are mean ±S.E.M of n=3-4 per group. >100 CMs were quantified per age group.",
    "ncbi_link": "MAO-A: 29253"
  },
  {
    "caption": "Mean % of TAF-positive nuclei (left graphs) or mean % of TAF (right graphs) in MnSOD+/+ vs MnSOD-/+, Data are mean ±S.E.M of n=3-4 per group. >100 CMs were quantified per age group.",
    "ncbi_link": "MnSOD: 20656"
  },
  {
    "caption": "Mean % of TAF-positive nuclei (left graphs) or mean % of TAF (right graphs) in Catalase+/+ vs. Catalase-/-, Data are mean ±S.E.M of n=3-4 per group. >100 CMs were quantified per age group.",
    "ncbi_link": "Catalase: 12359"
  },
  {
    "caption": "Mean % of TAF-positive nuclei (left graphs) or mean % of TAF (right graphs) in WT vs. POLG double mutant mice. Data are mean ±S.E.M of n=3-4 per group. >100 CMs were quantified per age group.",
    "ncbi_link": "POLG: 18975"
  },
  {
    "caption": "Comparison between the % of p16- or eGFP-positive CMs by RNA-in situ hybridization per plane in INK-ATTAC mice (28-29 month old) treated with vehicle or AP20187. Data are mean ± SEM of n=5 per age group. 100 CMs were analysed per mouse.",
    "ncbi_link": "eGFP: 
p16: 12578"
  },
  {
    "caption": "BACE1 or APP was immunoprecipitated from mouse brains and blotted with E4-PHA lectin (lower) or anti-BACE1 or APP antibodies (upper). hAPP indicates the APP23 transgenic mouse model for AD.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "APP metabolites from 3-month-old mouse brain membrane (A) or soluble (B) fractions were immunoblotted. The signal intensity was quantified (n = 4-5). All graphs show means ± SEM (*P < 0.05; Student's t-test for (A) βCTF and (B) sAPPα, and Mann-Whitney U-test for the others. P = 0.386 for APP, P = 0.602 for αCTF, P = 0.045 for βCTF, P = 0.218 for sAPPα, P = 0.022 for sAPPβ).",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "Amounts of Aβ40 or Aβ42 in the TBS-soluble or Gu-HCl-extractable fraction from (A) 3-month-old or (B) 12-month-old hAPP/Mgat3+/+, hAPP/Mgat3+/−, or hAPP/Mgat3−/− brains (n = 5). P = 0.015 for TBS Aβ40, P = 0.034 for TBS Aβ42, P = 0.001 and 0.012 for Gn-HCl Aβ40, P = 0.024 for Gn-HCl Aβ42 in (A), P = 0.040 for Gn-HCl Aβ40, P = 0.047 for Gn-HCl Aβ42 in (B).",
    "ncbi_link": "APP: 351
Mgat3: 17309"
  },
  {
    "caption": "Amounts of Aβ40 or Aβ42 in the TBS-soluble or Gu-HCl-extractable fraction from 3- to 4-month-old Mgat3+/+ or Mgat3−/− brains (n = 7-8). An outlier value was rejected by the Smirnov-Grubbs' test (P < 0.05). P = 0.045 for Gn-HCl Aβ40.",
    "ncbi_link": "Mgat3: 17309"
  },
  {
    "caption": "The Y-maze test was performed using 12-month-old male Mgat3+/+, Mgat3−/−, hAPP/Mgat3+/+, or hAPP/Mgat3−/− mice (n = 8-10). **P = 0.004 for Mgat3+/+ versus hAPP/Mgat3+/+, *P = 0.022 for hAPP/Mgat3+/+ versus hAPP/Mgat3−/−.",
    "ncbi_link": "APP: 351
Mgat3: 17309"
  },
  {
    "caption": "Immunostaining of 12-month-old mouse cerebral cortex for BACE1 and APP. A typical image in the vicinity of plaque-forming area is shown for hAPP/Mgat3+/+ brain. The area of co-localization was quantified using random images of cerebral cortex (n = 10). *P = 0.015.",
    "ncbi_link": "APP: 351
Mgat3: 17309"
  },
  {
    "caption": "MEFs were transfected with control siRNA or GGA3-siRNA and then immunoblotted for BACE1, GGA3, or GAPDH (loading control) (n = 6).",
    "ncbi_link": "GGA3: 260302"
  },
  {
    "caption": "Membrane fractions from 3-week-old Mgat3+/+, Mgat3−/−, and Bace1−/− mice were immunoblotted for CHL1 (upper), contactin-2 (middle), or syntaxin 6 (lower) (n = 4-5). The graphs show means ± SEM (**P < 0.01; two-way ANOVA with post hoc Tukey-Kramer test, P = 0.006 for Mgat3+/+ versus Bace1−/−, P = 0.008 for Mgat3−/− versus Bace1−/− in CHL1/syn6, P = 0.001 for Mgat3+/+ versus Bace1−/−, P = 0.002 for Mgat3−/− versus Bace1−/− in Contactin-2/syn6).",
    "ncbi_link": "Bace1: 23821
Mgat3: 17309"
  },
  {
    "caption": "B mRNA expression of adipogenesis-related factors of SVF cells isolated from iWAT of male mice. D mRNA expression of PPARγ, C/EBPα and FABP4 expression of 3T3-L1 cells treated with curcumin.",
    "ncbi_link": "C/EBPα: 12606
FABP4: 11770
PPARγ: 19016"
  },
  {
    "caption": "K Oil Red O staining of Vector or OE-ALKBH5 transfected 3T3-L1 cells. Differentiation was induced with curcumin up to day 8.",
    "ncbi_link": "ALKBH5: 268420"
  },
  {
    "caption": "E Oil Red O staining of control, ALKBH5-depleted and ALKBH5+TRAF4 depleted cells after induced for 8 days.",
    "ncbi_link": "ALKBH5: 268420
TRAF4: 22032"
  },
  {
    "caption": "Western blot analysis of YTHDF1, ALKBH5 and TRAF4 in control, ALKBH5-depleted and ALKBH5 + YTHDF1 depleted cells and quantification of protein levels normalized to β-actin expression.",
    "ncbi_link": "ALKBH5: 268420
YTHDF1: 228994"
  },
  {
    "caption": "L Oil Red O staining of control, ALKBH5-depleted and ALKBH5+YTHDF1 depleted cells on day 8 of differentiation.",
    "ncbi_link": "ALKBH5: 268420
YTHDF1: 228994"
  },
  {
    "caption": "M qPCR analysis of PPARγ, C/EBPα and FABP4 expression in cell β-Actin was used as an internal control.",
    "ncbi_link": "β-Actin: 
C/EBPα: 12606
FABP4: 11770
PPARγ: 19016"
  },
  {
    "caption": "C, D Western blot analysis of PPARγ protein levels in control and TRAF4 overexpressing cells in the absence or presence of MG132 or 3MA and quantification of protein levels normalized to β-actin expression.",
    "ncbi_link": "TRAF4: 22032"
  },
  {
    "caption": "E Ubiquitination of endogenous PPARγ in control and TRAF4 overexpressing cells were differentiated by treatment with DMI. Cells were treated with MG132 for 6 h.",
    "ncbi_link": "TRAF4: 22032"
  },
  {
    "caption": "B Results of immunoblotting  with immunoprecipitates  (IP) or whole-cell lysates from cells transfected with Bcl-2  and TMEM175  or its mutants TMEM175-V145A, TMEM175-R377V, as indicated. C Statistics of the relative TMEM175  protein levels normalized to GAPDH  in vector, TMEM175, TMEM175-V145A or TMEM175-R377V overexpressing HEK293T  cells. Data information: The data are presented as the mean ± SEM. Statistical significance was calculated with two-sided student's t-tests (C and is indicated with NS for not significant (P > 0.05), ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "ncbi_link": "Bcl-2: 596
TMEM175: 84286"
  },
  {
    "caption": "K (Upper) schematic diagram showing the strategy of TMEM175-KO in HEK293T  cells. 92 bp in exon 4 and intron 4 were removed from the tmem175  locus. (Lower) TMEM175  levels in the WT or TMEM175  KO cells were detected by Western-blotting.",
    "ncbi_link": "tmem175: 84286
TMEM175: 84286"
  },
  {
    "caption": "L CM-H2DCFDA (green) indicating cellular ROS  levels of WT or TMEM175  KO HEK293T  cells pre-treatment with vehicle or 10 μM HA14-1 for 20 min. Scale bars = 10 μm. M Statistics of CM-H2DCFDA  fluorescence intensity of (L). The n values represent the cell numbers counted within the same experiment. Data information: The data are presented as the mean ± SEM. Statistical significance was calculated with two-sided student's t-tests M) and is indicated with NS for not significant (P > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. In panel M, n value means the number of technical replicates.",
    "ncbi_link": "TMEM175: 84286"
  },
  {
    "caption": "F Fluorescence of G3BP1  excited with 488 nm in control (upper) and TMEM175-overexpressing (lower) cells. Scale bars = 10 μm. G Statistics of the numbers of puncta per cell (left) and the percentage of cells with puncta in (F). We counted 547 cells in Vector group from 37 different fields of view and 332 cells in TMEM175  group from 76 different fields of view. n value represents the number of different fields of view randomly selected in the same imaging experiment. Data information: The data are presented as the mean ± SEM. Statistical significance was calculated with two-sided student's t-test, and is indicated with ** for p < 0.01, and *** for p < 0.001. In panels G n value means the number of technical replicates.",
    "ncbi_link": "TMEM175: 84286"
  },
  {
    "caption": "H Co-localization  of mitochondrial  indicator TOM20-mCherry  and lysosomal  indicator  LysoTracker in WT (upper row) or TMEM175  KO (lower row) HEK293T  cells. Co-localization  of mitochondrion  and lysosome  is observed as a yellow colour in the merged image (marked by white arrows). Scale bars = 10 μm. I The number of merged puncta per cell in (H). We counted 139 cells in WT group from 38 different fields of view and 148 cells in TMEM175  KO group from 42 different fields of view. n value represents the number of different fields of view randomly selected in the same imaging experiment. Data information: The data are presented as the mean ± SEM. Statistical significance was calculated with two-sided student's t-test, and is indicated with ** for p < 0.01, and *** for p < 0.001. In panels I, n value means the number of technical replicates.",
    "ncbi_link": "TMEM175: 84286"
  },
  {
    "caption": "D TMEM175  mRNA levels in the midbrains  of WT or TMEM175  KO mice  were detected by RT-qPCR using SYBR  Green PCR Master Mix. Data information: The data are presented as the mean ± SEM. Statistical significance was analyzed with two-sided student's t-tests, and is indicated with NS for not significant (p > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "ncbi_link": "TMEM175: 72392"
  },
  {
    "caption": "E The knockout of TMEM175  in mouse  was verified by Western blot of brain  tissues.",
    "ncbi_link": "TMEM175: 72392"
  },
  {
    "caption": "F Representative TMEM175  basal lysosomal  currents recorded in macrophages  of WT or TMEM175-KO mice. Ψ is lysosomal membrane potential  (defined as Vcytosol - Vlumen). The currents were elicited with ramp voltage protocols (-100 to +100 mV in 1 s, Vh = 0 mV). G Statistics of the current amplitudes of (F). Data information: The data are presented as the mean ± SEM. Statistical significance was analyzed with two-sided student's t-tests, and is indicated with NS for not significant (p > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "ncbi_link": "TMEM175: 72392"
  },
  {
    "caption": "L Immunoblots of the TH  levels post-MPTP  treatment in WT and TMEM175  KO mouse midbrains. M Quantification of the relative TH  levels normalized to GAPDH  post-MPTP. Data information: The data are presented as the mean ± SEM. Statistical significance was analyzed with two-sided student's t-tests, and is indicated with NS for not significant (p > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "ncbi_link": "TMEM175: 72392"
  },
  {
    "caption": "N TH immunofluorescent labeling on substantia nigra slices of WT or TMEM175-KO mice  post-MPTP  treatment. Scale bars = 100 μm. O Statistics of the TH-positive neurons  in (N). Data information: The data are presented as the mean ± SEM. Statistical significance was analyzed with two-sided student's t-tests, and is indicated with NS for not significant (p > 0.05), * for p < 0.05, ** for p < 0.01, and *** for p < 0.001. n value means the number of biological replicates made for each data point.",
    "ncbi_link": "TMEM175: 72392"
  },
  {
    "caption": "D. ARPE-19 cells were transfected with 50 pmol of non-targeting siRNA (siNT) or 50 pmol of siRNA targeting ATG13 or ULK1. 48 hours post knockdown, cells were treated with 1 mM DFP for an additional 48 hours. Cell lysates were subject to immunoblotting with the indicated antibodies. Quantification is shown on the right.",
    "ncbi_link": "ATG13: 9776
ULK1: 8408"
  },
  {
    "caption": "A. Representative immunoblots of the indicated proteins in lysates of WT or HIF1α KO U2OS cells, treated with 1mM DFP for 48 hours.",
    "ncbi_link": "HIF1α: 3091"
  },
  {
    "caption": "B. Representative confocal images of WT or HIF1α KO U2OS cells stably expressing the pexo-QC reporter and treated with 1 mM DFP for 48 hours (left panel) and flow cytometry analysis of the mCherry/GFP ratio (right panel).",
    "ncbi_link": "HIF1α: 3091"
  },
  {
    "caption": "C. Representative immunoblots (left panel) and quantification (right panel) of the indicated proteins in lysates of WT or two NIX KO ARPE-19 clones (Cl), treated with 1 mM DFP for the indicated time (h, hours).",
    "ncbi_link": "NIX: 665"
  },
  {
    "caption": "D-E. Representative confocal images of WT or NIX KO ARPE-19 cells stably expressing the mito-QC reporter (D) or the pexo-QC reporter (E) treated with 1 mM DFP for 48 hours (left panel) and flow cytometry analysis of the mCherry/GFP ratio (right panel).",
    "ncbi_link": "NIX: 665"
  },
  {
    "caption": "F. Representative immunoblots (left panel) and quantification (right panel) of the indicated proteins. NIX KO ARPE-19 cells (Cl 31) stably expressing a pBabe empty vector (∅) or a pBabe NIX vector, were treated with 1 mM DFP for 48 hours prior lysis. Two biological replicates are shown in the immunoblot.",
    "ncbi_link": "NIX: 665"
  },
  {
    "caption": "A-B. Representative confocal images of untreated (CTRL) and DFP-treated ARPE-19 cells (1mM, 48 hours), stably expressing GFP-WT NIX (green) and stained with anti-catalase antibody (A, red) or anti-PMP70 antibody (B, red). At right, quantification of Pearson correlation coefficients between NIX and the peroxisomal markers catalase and PMP70, with or without DFP treatment for 48 hours. Peroxisomes enriched for GFP-NIX or having minimal signal for GFP-NIX are depicted with white arrowheads or white arrows, respectively.",
    "ncbi_link": "GFP: 
NIX: 665"
  },
  {
    "caption": "C. Representative confocal images of ARPE-19 cells stably expressing GFP-WT NIX, GFP-NIXΔTM or GFP-NIX TM only (green), treated with DFP (1mM) for 48 hours and immunostained with anti-catalase antibody (red). At right, quantification of Pearson correlation coefficients between the green and the red signal.",
    "ncbi_link": "GFP: 
NIX: 665"
  },
  {
    "caption": "B. Representative immunoblots of the indicated proteins in lysates of WT or HA-Parkin(PRKN)- ARPE-19 cells treated as in A.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "B. Representative immunoblots of the indicated proteins in lysates of NIX KO ARPE-19 cells (Cl 31) stably expressing a pBabe Flag vector (∅), a pBabe Flag-NIX vector (NIX), a pBabe Flag-NIX W36A\L39A vector (W36A\L39A) or a pBabe Flag-NIX S34E\S35E vector (S34E\S35E), and treated with 1 mM DFP for 48 hours prior lysis.",
    "ncbi_link": "Flag: 
NIX: 665"
  },
  {
    "caption": "A. Representative confocal images of optical section from WT and NIX KO mouse retina immunostained with peroxisomal markers (PMP70 and catalase) or a lysosomal marker LAMP1. Nuclei are coloured in white (DAPI). RPE, retinal pigment epithelium; ONL, outer nuclear layer; OPL, outer plexiform layer; INL; inner nuclear layer; IPL, inner plexiform layer; RGC, retinal ganglion cells. B. Quantification of signal area in the ONL and INL from images as A. Each data point represents a single mouse (n=3-4 per group).",
    "ncbi_link": "NIX: 12177"
  },
  {
    "caption": "(C) Asynchronous exponentially growing cells were treated with 0.2M HU (+HU), then HU was removed from the medium (-HU). SDS-PAGE of total protein extracts taken at the indicated times were used to detect the kinetic of Rad53 phosphorylation upshift (Rad53-P=**). Red and green asterisk indicate the time where mec1-S1991 phosphomutants show altered Rad53 recovery. A 5-fold dilution series of cells from exponential SC cultures of the indicated strains were spotted on SC +/- the indicated dose of HU.",
    "ncbi_link": "mec1: 852433"
  },
  {
    "caption": "Analysis of replication fork progression at the single-molecule level by DNA combing. (C) Representative images of DNA fibers. Green: ssDNA, red: BrdU. Scale bar corresponds to 20 kb. (D) Graph depict the distribution of BrdU track length. WT 90 min (n=427) and 180 min (n=483), mec1-S1991A 90 min (n=309) and 180 min (n=477).",
    "ncbi_link": "mec1: 852433"
  },
  {
    "caption": "(A) tRNA level measured by RT-qPCR in asynchronous (async.) culture and after 90 min on HU in the indicated strains. Expression is normalized to ACT1. The repression is expressed as a ratio of HU treated/asynchronous cells in percent.",
    "ncbi_link": "ACT1: "
  },
  {
    "caption": "(A) Preparations of chromatin-bound proteins were prepared in triplicate and subjected to SDS-PAGE and immunoblotting with the indicated antibodies in a strain that either does or does not express Rpb3-TAP Quantification of chromatin-bound Rpb1-S2P and Rpb1-S5P is shown on the right. Mcm2 is used as a loading control.",
    "ncbi_link": "TAP: 
Rpb3: 854791"
  },
  {
    "caption": "(F,G) A 10-fold dilution series of cells from exponential SC cultures of the indicated strains were spotted on SC +/- 200mM of HU. A high level of HU was used to be able to demonstrate robust suppression of the mec1-S1991A phenotype. (G) Histogram presents quantification of 2 independent HU sensitivity assays with mean and individual data point values indicated for each yeast dilution.",
    "ncbi_link": "mec1: 852433"
  },
  {
    "caption": "(B) Amongst the Mec1-S1991-dependent phosphopeptides on HU, factors involved in transcription are highlighted.",
    "ncbi_link": "Mec1: 852433"
  },
  {
    "caption": "(E) Position relative to the nuclear envelope (Zone 1 of the lacO-tagged GAL1-GAL10 locus in the indicated strains grown either 12h on glucose, or 90 min galactose or galactose + 0.2M HU. The third panel shows the relative retention at the nuclear periphery (Zone 1) on galactose + HU. The number of cells is >300 for each condition.",
    "ncbi_link": "lacO: 
GAL1: 852308
GAL10: 852307"
  },
  {
    "caption": "A S. cerevisiae wt or hsp42Δ cells expressing mCherry‐VHL (red) and GFP‐luciferase‐DM‐NLS (green) were grown at 30°C and shifted to 37°C for 90 min. MG132 was added prior to temperature upshift. Changes in protein localizations were recorded. DNA was stained by DAPI (blue).",
    "ncbi_link": "luciferase: 
hsp42: 851751"
  },
  {
    "caption": "B S. cerevisiae wt cells or hsp42Δ cells expressing GFP‐VHL (green) were treated as in (A). Nuclear membranes were visualized by Nsp1immunofluorescence microscopy labeling (red).",
    "ncbi_link": "hsp42: 851751"
  },
  {
    "caption": "C S. cerevisiae wt cells or hsp42Δ cells expressing mCherry‐VHL (red) and GFP‐Nup49 (green) were treated as in (A). Three‐dimensional reconstructions of respective cells are given.",
    "ncbi_link": "hsp42: 851751"
  },
  {
    "caption": "A-D Cryo‐sections of (A) S. cerevisiae wt cells expressing GFP‐luciferase‐DM‐NLS, (B) hsp42Δ cells expressing GFP‐VHL. Sections were immunogold‐labeled with GFP‐specific antibodies. Gold particles are marked (black arrows). Electron‐dense regions represent protein aggregates (A). Locations of cytosol (C), nuclear envelope (NE, orange arrows), and nucleus (N) are given. Scale bars, 200 nm.E, F Average numbers of gold particles associated with nuclear and cytosolic protein aggregates or distributed throughout the cytosol or nucleus were determined.",
    "ncbi_link": "luciferase: 
hsp42: 851751"
  },
  {
    "caption": "A-D Cryo‐sections of S. cerevisiae (C, D) wt or hsp42Δ cells expressing Hsp104‐GFP. Sections were immunogold‐labeled with GFP‐specific antibodies. Gold particles are marked (black arrows). Electron‐dense regions represent protein aggregates (A). Locations of cytosol (C), nuclear envelope (NE, orange arrows), and nucleus (N) are given. Scale bars, 200 nm.E, F Average numbers of gold particles associated with nuclear and cytosolicprotein aggregates or distributed throughout the cytosol or nucleus were determined.",
    "ncbi_link": "hsp42: 851751"
  },
  {
    "caption": "B tGnd1‐GFP is stabilized in ubr1Δ san1Δ cells. S. cerevisiae wt and ubr1Δ san1Δ mutant cells expressing tGnd1‐GFP were grown at 30°C. Cycloheximide was added, and protein levels were determined at the indicated time points by Western blot using GFP‐specific antibodies. Zwf1 levels are given as a loading control.",
    "ncbi_link": "san1: 851721
ubr1: 853096"
  },
  {
    "caption": "C Ubiquitination status of tGnd1‐GFP expressed in S. cerevisiae wt and ubr1Δ san1Δ cells was determined by GFPpull‐down and Western blot analysis using ubiquitin‐specific antibodies. Levels of isolated tGnd1‐GFP after GFPpull‐down were determined by Western blot using GFP‐specific antibodies and are given as a control.",
    "ncbi_link": "san1: 851721
ubr1: 853096"
  },
  {
    "caption": "D S. cerevisisae wt, ubr1Δ san1Δ, and ubr1Δ san1Δ btn2Δ cells expressing tGnd1‐GFP (green) were grown at 30°C. DNA and nuclear envelopes were visualized by coexpressing Htb1‐mCherry or Nic96‐mCherry, respectively (red). The fraction of cells showing specific tGnd1‐GFP foci numbers per cell was determined. INQ formation in cells containing tGnd1‐GFP foci was determined (% cells with INQ) based on close vicinity of tGnd1‐GFP foci to Htb1‐mCherry or localization inside Nic96‐mCherry signals, yielding comparable results. Scale bars, 2 μm.",
    "ncbi_link": "btn2: 853043
san1: 851721
ubr1: 853096"
  },
  {
    "caption": "A, B S. cerevisiae hsp42Δ and hsp42Δ nup42Δ cells expressing mCherry‐VHL (red) were grown at 30°C and shifted to 37°C in the presence of MG132. Changes in protein localization were monitored. Scale bars, 2 μm. The total number of mCherry‐VHL foci per cell was determined.",
    "ncbi_link": "hsp42: 851751
nup42: 851774"
  },
  {
    "caption": "S. cerevisiae hsp42Δ and hsp42Δ tet‐off sis1 cells expressing GFP‐VHL were grown for 20 h in the absence (−Dox) or presence (+Dox) of doxycycline at 30°C and shifted for 90 min to 37°C in the presence of MG132. Changes in protein localization were monitored. DNA was stained by DAPI (blue). The total number of GFP‐VHL foci per cell and frequencies (%) of INQ formation were determined. Scale bars, 2 μm.",
    "ncbi_link": "hsp42: 851751"
  },
  {
    "caption": "B S. cerevisiae wt, hsp42Δ, sti1Δ, and hsp42Δ sti1Δ cells expressing GFP‐VHL were grown at 30°C and shifted to 37°C in the presence of MG132. Changes in protein localization were monitored. The total number of GFP‐VHL foci per cell and frequencies (%) of INQ formation were determined. Scale bars, 2 μm.",
    "ncbi_link": "hsp42: 851751
sti1: 854192"
  },
  {
    "caption": "A, B S. cerevisiae wt, hsp42Δ, btn2Δ, and hsp42Δ btn2Δ cells expressing GFP‐VHL (green, A) or GFP‐luciferase‐DM‐NLS (green, B) were grown at 30°C and shifted to 37°C for 90 min in the presence of MG132, and protein localizations were recorded. DNA was stained by DAPI (blue), and the nuclear envelope was stained by Nsp1immunofluorescence microscopy (red). Solubilities of GFP‐VHL and GFP‐luciferase‐DM‐NLS were determined after stress application by Western blot using GFP‐specific antibodies. Solubility of actin was determined as a control. T, total fraction; S, soluble fraction; P, pellet fraction. Scale bars, 2 μm.",
    "ncbi_link": "luciferase: 
btn2: 853043
hsp42: 851751"
  },
  {
    "caption": "C S. cerevisiae wt, hsp42Δ, btn2Δ, and hsp42Δ btn2Δ cells expressing mCherry‐VHL were heat‐shocked to 38°C. Upon return to 30°C, protein synthesis was stopped by cycloheximide (CHX) addition and degradation of mCherry‐VHL was monitored by Western blot analysis. The stability of GFP‐luciferase‐DM‐NLS expressed in S. cerevisiae wt and btn2Δ cells was determined accordingly. Ccs1 or Zwf1 levels are given as loading controls.",
    "ncbi_link": "luciferase: 
btn2: 853043
hsp42: 851751"
  },
  {
    "caption": "D S. cerevisiae hsp42Δ btn2Δ cells expressing either GFP or LuciDM‐GFP and Htb1‐mCherry were grown at 30°C and heat‐shocked to 37°C for 30 min. Line intensity plots of luciferase‐DM‐GFP and Htb1‐mCherry before and after heat shock are given. The ratio of nuclear and cytosolic luciferase‐DM‐GFP fluorescence intensity was determined at 30°C and 37°C (n > 25). Scale bars, 2 μm.",
    "ncbi_link": "luciferase: 
btn2: 853043
hsp42: 851751"
  },
  {
    "caption": "C S. cerevisiae btn2Δ hsp42Δ Hsp42‐NLS cells expressing GFP‐VHL (green) were grown at 30°C and heat‐shocked to 37°C for 30 min in the presence of MG132. Changes in protein localizations were recorded. DNA was stained by DAPI (blue). The total number of GFP‐VHL foci per cell and frequencies (%) of INQ formation were determined. Scale bars, 2 μm.",
    "ncbi_link": "btn2: 853043
hsp42: 851751
Hsp42: 851751"
  },
  {
    "caption": "D S. cerevisiaebtn2Δ hsp42Δ Hsp42‐NLS cells expressing mCherry‐VHL (red) were treated as described in (C). The nuclear membrane was visualized by Nsp1 immunofluorescence (green) and colocalization of mCherry‐VHL foci with Hsp42 was probed by Hsp42 (green) immunofluorescence microscopy. DNA was stained with DAPI (blue). Scale bars, 2 μm.",
    "ncbi_link": "btn2: 853043
hsp42: 851751
Hsp42: 851751"
  },
  {
    "caption": "B, C S. cerevisiae wt and btn2Δ cells expressing Hos2‐GFP (green, B) or GFP‐VHL (green, C) were grown at 30°C and treated with MMS. Changes in protein localizations were recorded at the indicated time points. DNA was stained by DAPI (blue). The total number of GFP‐VHL foci per cell and frequencies (%) of INQ formation were determined.",
    "ncbi_link": "btn2: 853043"
  },
  {
    "caption": "C. Cells were treated with BMP2 for 1 h. D. Cells were stimulated with increasing (doubling) doses of BMP4/7 (0.625-20 ng/mL) for 1 h.  Data information: In all cases, whole cell extracts were Western blotted  using the indicated antibodies. Representative experiments are shown. The levels   of pSMAD1/5 relative to  Actin were determined and are expressed as a fold change relative to the parental HEK293T  untreated sample or normalized to the 20 ng/mL ligand  dose  in parental  HEK293T cells Act, Activin A; Par, parental  HEK293T  cells,  KO1, ACVR1 KO clone 1.",
    "ncbi_link": "ACVR1: 90"
  },
  {
    "caption": "D. Parental HEK293T, S2/3 dKO1 and HOM1 cells were treated with Activin A  for the indicated times. Data information: ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. The p-values are from two-way ANOVA with Dunnett's post-hoc test. In D quantifications are from a representative experiment and are the intensities of  pSMAD1/5 normalized to Actin, expressed as fold change relative to untreated cells for each clone. In all panels, Western blots of whole cell lysates were probed with the antibodies indicated.",
    "ncbi_link": "S2: 4087"
  },
  {
    "caption": "A. Parental HEK293T, ACVR2A KO, ACVR2B KO, ACVR2A/B dKO, HOM1, HOM1 ACVR2A  KO, HOM1 ACVR2B KO, HOM1 ACVR2A/B dKO cells were treated with Activin A  or BMP2 for 1 h. Data information: In all panels, Western blots of whole cell lysates were probed with the antibodies indicated. Representative experiments are shown. Par, parental HEK293T  cells.",
    "ncbi_link": "ACVR2A: 92
ACVR2B: 93"
  },
  {
    "caption": "C. NIH-3T3 cells were either  untransfected or  transfected  with either FLAG-SMAD1 or  GFP-SMAD3 together with Opto-ACVR1B*. Post  transfection, cells were either kept in the  dark or exposed to blue light for 1 h, in the presence or absence of 50 µM SB-505124 or 1 µM LDN-193189. Data information: In all panels, Western blots of whole cell lysates were probed with antibodies against pSMAD1/5 (that detected both endogenous and pFLAG-SMAD1), SMAD1 (which detects both endogenous and FLAG-SMAD1), HA (which detects the Opto-receptors), pSMAD3 (which detects pGFP-SMAD3), SMAD3 (which detects GFP-SMAD3) and either Tubulin  or Actin as the loading controls. Lane numbers are given below each blot for clarity. ",
    "ncbi_link": "ACVR1B: 11479"
  },
  {
    "caption": "I. Average brightness of His-Activin A-Atto647N in  ICR-B169 and  HSJD-DIPG-007 cells alone or with pre-incubation with 1.5 µg/mL of rhACVR2A Fc and 15 µg/mL of rhACVR2B Fc. Source data is in Fig. EV4B-F. Means ± SEM are plotted. Each point represents one analyzed image, collected from 2-4 biological replicates. Data information: In H and I the p values are from one-way ANOVA with Tukey's post hoc correction. *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001.",
    "ncbi_link": "ACVR2A: 92
ACVR2B: 93"
  },
  {
    "caption": "CL levels after PTPIP51 depletion and reconstitution were monitored. A doxycycline-induced shRNA expression system was used to deplete the PTPIP51 protein in HeLa cells. Left, western blot analysis of HeLa cells in which PTPIP51 was depleted and restored. β-ACTIN was used as the loading control. Right, the mitochondrial CL level (nmol/mg) according to PTPIP51 expression. To reconstitute PTPIP51, the full-length PTPIP51 gene was transiently expressed. The data are presented as the mean ± SD of technical triplicate experiments from one representative experiment (n = 3), and p-values calculated using Student's t-test are shown.",
    "ncbi_link": "PTPIP51: 55177"
  },
  {
    "caption": "Quantification of CL in mitochondria using lipidomic analysis after PTPIP51 depletion and reconstitution. Color codes for each sample were presented in the lower right subpanel. Experiments were technically repeated three times, and the results are represented as the means ± SD of technical replicates (n = 3). *p < 0.05; **p < 0.01 (Student's t-test). Quality control (QC) samples, which were pooled identical aliquots of the mitochondria samples, were measured four times throughout the run for data reproducibility. Upper right, western blot analysis of HeLa cells in which PTPIP51 WT or ∆FFAT mutant were depleted and restored. β-Actin was used as a loading control.",
    "ncbi_link": "PTPIP51: 55177"
  },
  {
    "caption": "B Analysis of the methylation status at nephrin gene promoter in podocytes cultured in normal, high glucose or high mannitol at the indicated time points. U, unmethylated-specific primers; M, methylated-specific primers.",
    "ncbi_link": "nephrin: 54631"
  },
  {
    "caption": "D Effect of pargyline hydrochloride on high glucose-mediated DNA methylation at nephrin gene promoter. Genomic DNA samples from the treated podocytes were analyzed for methylation status of nephrin gene promoter by methylation-specific PCR.",
    "ncbi_link": "nephrin: 54631"
  },
  {
    "caption": "A Effect of KDM6A knockdown on the expression of nephrin and WT-1 in immortalized mouse podocytes cultured under high glucose conditions. Western blot analyses were performed using protein lysates of podocytes that were transfected with scrambled siRNAs or KDM6A-specific siRNAs, and cultured in high glucose (HG) or high mannitol (Mann) for 48 hours. *P < 0.05 versus normal controls, #P < 0.05 versus control siRNA with HG incubation (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "B Effect of KDM6A overexpression on expression levels of nephrin and WT-1. Immortalized podocytes were transfected with the KDM6A expression plasmid or the empty vector control for 48 hours, and the expression levels of KDM6A, nephrin and WT-1 in these transfected podoytes were analyzed by immunoblotting. *P < 0.05 versus vector controls (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "C Changes in H3K27me3 levels in podocytes after treatment with high glucose, the combination of high glucose and KDM6A knockdown, or KDM6A overexpression for 48 hours. *P < 0.05 versus normal controls, #P < 0.05 versus control siRNA with HG incubation (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "D Changes in DNA methylation at nephrin gene promoter by high glucose, by the combination of high glucose plus KDM6A knockdown, or by KDM6A overexpression in immortalized podocytes. U, unmethylated-specific primers; M, methylated-specific primers. Experiments were repeated three times and a representative gel from one experiment is shown.",
    "ncbi_link": "KDM6A: 22289
nephrin: 54631"
  },
  {
    "caption": "F Changes in DNA methylation at nephrin gene promoter by GSK-J4 (40 μM) in immortalized podocytes. U, unmethylated-specific primers; M, methylated-specific primers.",
    "ncbi_link": "nephrin: 54631"
  },
  {
    "caption": "Relative mRNA levels of KDM6A, nephrin and WT-1, normalized to β-actin, expressed in kidney glomeruli of normal and diabetic mice at 4, 8 and 12 weeks after diabetic induction. *Significant differences (P < 0.05) compared with normal controls (Wilcoxon two-sample test; n =8 each).",
    "ncbi_link": "β-actin: 
KDM6A: 22289
nephrin: 54631
WT-1: 22431"
  },
  {
    "caption": "A Quantitative RT-PCR evaluation of KDM6A mRNA expression in kidney glomeruli isolated from wild-type and KDM6A-knockout (KO) mice. *P < 0.05, significant difference versus wild-type controls (Wilcoxon two-sample test; n = 8).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "B Western blot analysis of KDM6A expression in glomeruli and podocytes isolated from wild-type and KDM6A-KO mice. Presented experiments were performed at least three times independently.",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "C Changes in body weights and levels of blood glucose in wild-type or KDM6A-KO mice with or without STZ treatment. No significant differences in body weights or blood glucose levels between wild-type and KDM6A-KO mice with diabetes were observed during the 8-week experimental period (Wilcoxon two-sample test; n = 8).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "D Levels of urinary protein excretion, weights of kidney and levels of HbA1c in wild-type and KDM6A-KO mice with or without STZ treatment (at 8 weeks after the onset of diabetes). The mean relative kidney weight (%) shown in the study is determined as the percent of kidneys out of total body weight, and the HbA1c level is defined as the ratio of HbA1c to the total hemoglobin (% HbA1c; DCCT unit). *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 8).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "E Immunofluorescence images of kidney sections stained with KDM6A and nephrin in wild-type (WT-NC), KDM6A-KO (KO-NC), STZ-treated wild-type (WT-DM), or STZ-treated KDM6A-KO (KO-DM) mice. Scale bars, 20 μm. *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "F Immunofluorescence images of kidney sections stained with KDM6A and H3K27me3 in wild-type (WT-NC), KDM6A-KO (KO-NC), STZ-treated wild-type (WT-DM), or STZ-treated KDM6A-KO (KO-DM) mice. Scale bars, 20 μm. *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "I Effect of high glucose on the expression of podocyte-related markers in primary cultured podocytes isolated from wild-type or KDM6A-KO mice. The primary podocytes isolated from wild-type or KDM6A-KO mice were cultured in normal or high glucose (30 mM) for 48 hours. Protein lysates from the cultured podocytes were subjected to Western blot analysis with the indicated antibodies. *P < 0.05 versus wild-type podocytes in normal glucose, #P < 0.05 versus wild-type podocytes in high glucose (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "A Screening of the potential KDM6A-regulated transcriptional factors involved in repression of nephrin expression. After transduction with a control lentiviral vector or a lentiviral vector expressing KDM6A into primary podocytes for 48 hours, intracellular RNAs were isolated and used for RNA sequencing (RNA-Seq) analysis. The transcript expression patterns of 86 selected transcriptional factors from three independent RNA-Seq experiments are presented in a heat map. Notably, among these 86 selected genes, KLF10 is the most upregulated gene.",
    "ncbi_link": "KDM6A: 22289
KLF10: 21847"
  },
  {
    "caption": "B Validation of increased KDM6A and KLF10 expression in primary podocytes that were infected with an empty lentiviral vector or KDM6A-expressing lentiviral vector for 48 hours. *P < 0.05 versus the empty vector control (Wilcoxon two-sample test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "D Effect of KLF10 knockdown on high glucose-mediated reduction of nephrin in primary podocytes. As noted, knockdown of KLF10 prevented downregulation of nephrin and upregulation of KDM6A in high glucose-treated podocytes. *P < 0.05 versus normal controls, #P < 0.05 versus control siRNA with HG incubation (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "F Immunofluorescence images of KLF10 and nephrin in renal sections of wild-type or KDM6A-KO mice with or without STZ treatment. Scale bars, 20 μm. *P < 0.05 versus the untreated wild-type group, #P < 0.05 versus the STZ-treated wild-type group (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "H Western blot analysis of KDM6A, KLF10 and nephrin expression in primary podocytes isolated from wild-type or KDM6A-KO mice with or without STZ treatment. *P < 0.05 versus the untreated wild-type group, #P < 0.05 versus the STZ-treated wild-type group (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KDM6A: 22289"
  },
  {
    "caption": "ChIP analysis of KLF10, acetyl-Histone H4 (H4-Ac), Dnmt1 and Dnmt3 binding to nephrin gene promoter. ChIP assays were carried out using cross-linked chromatin from primary podocytes that were cultured in normal or high glucose conditions. *P < 0.05, significant difference versus the normal control group (Wilcoxon two-sample test; n = 3).",
    "ncbi_link": "nephrin: 54631"
  },
  {
    "caption": "J Modulation of podocyte-specific marker expression in primary podocytes by KLF10 overexpression. Ectopic overexpression of KLF10 in primary podocytes significantly repressed various podocyte-specific markers, but conversely increased KDM6A expression. *P < 0.05 versus the empty vector control (Wilcoxon two-sample test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "A Quantitative RT-PCR evaluation of KLF10 mRNA expression in kidney samples of wild-type and KLF10-knockout (KO) mice. **P < 0.0001, significant difference versus wild-type controls (Wilcoxon two-sample test; n = 8).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "B Western blot analysis of KLF10 expression in kidney samples of wild-type or KLF10-KO mice treated with or without STZ at 8 weeks after the onset of diabetes.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "C Changes in body weight and blood glucose levels in wild-type or KLF10-KO mice with or without STZ treatment. No significant differences in body weights or blood glucose levels between diabetic wild-type mice and diabetic KLF10-KO mice were detected (Wilcoxon two-sample test; n = 8).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "D Levels of urinary protein excretion, weights of kidney and levels of HbA1c in wild-type or KLF10-KO mice with or without STZ treatment. The mean relative kidney weight (%) shown in the study is determined as the percent of kidneys out of total body weight, and the HbA1c level is defined as the ratio of HbA1c to the total hemoglobin (% HbA1c; DCCT unit). *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 8).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "E Immunofluorescence images of kidney sections stained with KLF10 and nephrin in wild-type or KLF10-KO mice untreated or treated with STZ. Scale bars, 20 μm. *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "F Immunofluorescence images of kidney sections stained with KLF10 and KDM6A in wild-type or KLF10-KO mice untreated or treated with STZ. Scale bars, 20 μm. *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "G Immunofluorescence staining of F-actin and KLF10 in primary podocytes isolated from the wild-type or KLF10-KO mice untreated or treated with STZ. Presented experiments were performed at least three times independently. Scale bars, 20 μm.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "H Immunofluorescence staining of F-actin and KDM6A in primary podocytes isolated from the wild-type or KLF10-KO mice untreated or treated with STZ. Presented experiments were performed at least three times independently. Scale bars, 20 μm.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "I Western blot analysis of KLF10, KDM6A, nephrin and WT-1 expression in primary podocytes isolated from the wild-type or KLF10-KO mice that were untreated or treated with STZ. *P < 0.05 versus untreated wild-type controls, #P < 0.05 versus STZ-treated wild-type mice (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "J Western blot analysis of KLF10, KDM6A, nephrin and WT-1 expressed in podocytes treated with TGF-β1 or the combination of TGF-β1 and KLF10 knockdown. *P < 0.05 versus normal controls, #P < 0.05 versus control siRNA with TGF-β1 treatment (Parametric ANOVA and a Bonferroni post hoc test; n = 3).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "C Levels of KDM6A and KLF10, nephrin mRNAs in urine exosomes of diabetic nephropathy patients and non-diabetic controls. Relative mRNA levels in human urinary exosomes were normalized to 18S rRNA. Horizontal lines are medians. *P < 0.05, **P < 0.01, and ***P < 0.001 by Wilcoxon two-sample test (n = 12 for each group).",
    "ncbi_link": "18S rRNA: 
KDM6A: 7403
KLF10: 7071
nephrin: 4868"
  },
  {
    "caption": "(C) HelaWT, HeLaHexaKO, HeLaLC3TKO, HeLaGABATKO stably expressing HT-LC3B were starved with EBSS for 90min or 6h. Cell were incubated with ± HaloTag ligand fluorescently labeled with TMR. In-gel fluoresce (TMR) and Western blots (anti-HaloTag antibody) of freed HaloTagTMR were imaged and band intensity quantified. (D) Quantification of in-gel fluorescence band intensity and Western blot with anti-Halo antibody.",
    "ncbi_link": "GABA: 11337
LC3: 81631///440738///84557"
  },
  {
    "caption": "(C) SolVit complementation/rescue analysis (quantification) of acceptor HeLaLC3TKO-HT-LC3B PNS with donor PNS from HeLaWT, HeLaLC3TKO or HelaGABATKO cells ±ATP, 1 h, 37˚C. (D) SolVit complementation/rescue analysis (quantification) of acceptor HeLaGABATKO-HT-LC3B PNS with donor PNS from HeLaWT, HeLaLC3TKO and HelaGABATKO cells ±ATP, 1 h, 37˚C.",
    "ncbi_link": "GABA: 11337
LC3: 440738///81631///84557"
  },
  {
    "caption": "(G) Co-IP analyses in HEK293T cells expressing FLAG-VPS37AFL, FLAG-VPS37AdeltaN (1-90), VPS37AdeltaN(1-20) and FLAG-Nter-EGFP and co-transfected with GFP-GABA. 5% of input was loaded. (H) Co-IP analyses in HEK293T cells expressing FLAG-VPS37AFL, FLAG-VPS37AdeltaN (1-90), VPS37AdeltaN(1-20) and FLAG-Nter-EGFP and co-transfected with GFP-LC3A. 5% of input was loaded.",
    "ncbi_link": "EGFP: 
FLAG: 
GFP: 
GABA: 11337
LC3A: 84557
VPS37A: 137492"
  },
  {
    "caption": "(I) Complementation of VPS37A KO with VPS37A constructs that have or lack mATG8-binding region. Quantification of MIL+ puncta in Huh7WT HT-LC3B (circles) and Huh7VPS37AKO HT-LC3B cells (squares), transfected with empty FLAG, full length VPS37A (FLAG-VPS37AFL) or mutant VPS37A (FLAG-VPS37AdeltaN(1-20)). Data information: Statistical significance was determined by one-way ANOVA followed by Tukey's multiple comparison test. All values are means ± SD, n = 3 biologically independent replicates, each HCM experiment: 1,000 valid primary objects/well, 6 wells/sample. (J) HCM images, examples corresponding to Fig 5I, scale bar, 10 μm.",
    "ncbi_link": "FLAG: 
VPS37A: 137492"
  },
  {
    "caption": "(B) MPL-MIL HCM assay in Huh7WT and Huh7VPS37AKO stably expressing HT-LC3B. Quantification: (B i) membrane-permeant HT ligand (MPL) staining of LC3B-II sequestered within sealed membranes. (B ii) MIL staining of membrane-bound HT-LC3B-II accessible to the cytosol and (B iii) MIL/MPL puncta ratio.",
    "ncbi_link": "VPS37A: 137492"
  },
  {
    "caption": "(F-H) MPL-MIL HCM assay in Huh7WT (control or CHMP2A siRNA-treated cells; immunoblot in F) stably expressing HT-LC3B during CCCP-induced mitophagy in ± BafA1 (100 nM). (G) Quantification: (G i) MPL+ sealed membranes; (G ii) MIL+ unsealed membranes; (G iii) MIL/MPL puncta ratio. (H) HCM images corresponding to panel G.",
    "ncbi_link": "CHMP2A: 27243"
  },
  {
    "caption": "(C) Quantification of MIL+ puncta (unsealed/ligand-accessible LC3B+ membranes) in Huh7WT (circles) or Huh7VPS37AKO (squares) cells stably expressing HT-LC3B. Cells were transfected with empty FLAG vector, FLAG-VPS37A full length (VPS37AFL), FLAG-VPS37AdeltaN(1-90), or FLAG-VPS37AdeltaN(1-20) constructs. CCCP, 6 h treatment. (D) HCM images of Huh7VPS37AKO HT-LC3B with VPS37A constructs (VPS37AFull, FLAG-VPS37AdeltaN(1-90), FLAG-VPS37AdeltaN(1-20) and FLAG-VPS37ANter-GFP). FLAG-Tag VPS37A constructs, expression detected as red; and MIL+ puncta, pseudo color green. Data information: Statistical significance was determined by one-way ANOVA followed by Tukey's multiple comparison test. All values are mean ± SD, n = 3 biologically independent experiments, each HCM experiment: 1,000 valid primary objects/cells per well, 6 wells/sample, Scale bar, 10μm. ",
    "ncbi_link": "FLAG: 
GFP: 
VPS37A: 137492"
  },
  {
    "caption": "Preadipocytes  bearing the shRNA targeting  Pgc1α were induced differentiation with or without 1mM  asparagine. Protein expression was analyzed on day 6. n=3 biological replicates.",
    "ncbi_link": "Pgc1α: 19017"
  },
  {
    "caption": "Brown preadipocytes were infected by lentiviral shRNAs against  Asns. Cells were differentiated in culture media with or without 1mM asparagine. Western blot  was performed on day 6.",
    "ncbi_link": "Asns: 27053"
  },
  {
    "caption": "Brown preadipocytes were knocked down Raptor following standard induction to mature adipocytes with or without asparagine supplementation. Protein expression analysis was performed on day 6.",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "(A) A431 WT and SKO cells -/+ GFP-fused WT or A212P-seipin were delipidated, treated with OA for 1 h, fixed and stained with LD540. Maximum intensity projections of deconvolved confocal z-stacks. Dashed lines indicate cell boundaries. (B) Analysis of LD areas of cells treated as in (A) and imaged with widefield microscopy. Bars: % of LDs/cell in indicated size category, mean ± SEM, n=57-61 cells/genotype, 2 experiments, p**< 0.005 (unpaired T-test).",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(C) SKO + WT- or A212P-seipin-GFP cells were stained for calreticulin. Maximum intensity projections of deconvolved confocal z-stacks.",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(D) SKO + WT- or A212P-seipin-GFP cells were grown in standard growth medium, fixed and stained with anti-GFP antibodies. Widefield and STORM images.",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(E) SKO + WT-seipin-GFP cells were delipidated and treated with OA for 1h, fixed and stained with LipidTox Red. Single focal plane of a 3D-SIM z-stack. (F) Analysis of (E), bars: % of LDs/cell with the indicated number of WT-seipin-GFP punctae associated, mean ± SEM, n=12 cells (693 LDs), 2 experiments, p**< 0.005 (Tukey multiple comparisons test).",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(G) SKO + WT- or A212P-seipin-GFP cells were delipidated, incubated with OA for 30 min, and immunolabelled for TEM with anti-GFP antibodies. Black arrowheads: immuno-gold, orange arrowheads: ER-LD junctions. See also Appendix Fig S3. (H) Analysis of (G), bars: relative labeling index in different cellular compartments, n=3456-4512 immuno-gold clusters. Distribution of both WT- and A212P-GFP-seipin immunolabel is non-random (chi square test, **p<0.005), but there is significant enrichment of WT- but not A212P-seipin-GFP at ER-LD contacts relative to the ER (binomial test, **p<0.005). See also Appendix Table S1 and S2.",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(I) WT and SKO cells stably expressing HSP47-APEX were delipidated, treated with OA for 1 h and processed for SB-EM. 3D models of LDs and surrounding ER and mitochondria profiles shown on top of a block face image from SB-EM dataset. Insets are representative cross sections from modeled area highlighting the ER-LD association. Red= LD, Yellow= ER, Green=mitochondria. (J) Analysis of LDs from (I). Black lines indicate median, boxes third quartiles, n= 98-227 LDs. (K) Analysis of LDs displaying no ER contacts from (I). Bars: mean % of LDs in ROIs not in proximity to the ER, ± SEM, n= 11-16 ROIs/genotype, **p<0.005 (unpaired T-test).",
    "ncbi_link": "HSP47: 871"
  },
  {
    "caption": "(A) A431 WT cells with seipin tagged at its chromosomal locus with sfGFP and stably expressing ER marker plasmid (BFP-KDEL) were delipidated and treated with OA for 20 h, fixed and stained with LipidTox Red. Single confocal plane of an airyscan z-stack.",
    "ncbi_link": "seipin: 26580"
  },
  {
    "caption": "(A) Two control and BSCL2fibroblast cell lines were delipidated and treated with OA for 1 h, fixed and stained with LD540. Maximum intensity projections of deconvolved confocal z-stacks.",
    "ncbi_link": "BSCL2: 26580"
  },
  {
    "caption": "(B) Control and BSCL2fibroblasts were incubated with OA for 75-90 min, LDs were stained with LD540 and cells imaged live with widefield microscopy. Insets show overlay of two subsequent frames (400 ms apart). (C) Analysis of (B). Bars = 1 - [Pearson's colocalization coefficient between subsequent frames/ROI], ± SEM, n=120-140 ROIs (60-70 cells), 2 experiments, **p<0.005 (Mann Whitney test).",
    "ncbi_link": "BSCL2: 26580"
  },
  {
    "caption": "(D) Control and BSCL2fibroblasts were transfected with ER marker plasmid (sfGFP-ER-3) for 24 h and treated with OA for 10-60 min. LipidTox Deep Red or LD540 was used to label LDs and cells were imaged live by airyscan microscopy. Examples of LDs with high mobility are shown, blue arrowheads indicate a LD moving along the ER, orange arrowheads indicate LDs moving independent of the ER. (E) Analysis of ER associated movement of LDs from live airyscan microscopy as in (D). Bars: % of LDs/ROI displaying indicated mode of movement, mean ± SEM, n= 50-42 ROIs (218-374 LDs), 2 experiments, **p<0.005 (Mann Whitney test).",
    "ncbi_link": "BSLC2: 26580"
  },
  {
    "caption": "(F) Control and BSCL2fibroblasts were treated with OA for 1 h, fixed and stained with anti-ACSL3 antibodies and LD540. Representative sections of peripheral ER areas, maximum intensity projections of deconvolved confocal z-stacks. (G) Analysis of (F), with insets illustrating assigned categories of ACSL3 LD association. Insets are the same as in Fig 4F. Bars: % of LDs/ROI showing the category indicated, mean ± SEM, n= 11-10 peripheral ROIs from 11-10 cells/group (1200-2019 LDs), 2 experiments, **p<0.005 (unpaired T-test).",
    "ncbi_link": "BSCL2: 26580"
  },
  {
    "caption": "C Hsf1(1-408) with a deleted TAD is dissociated from HSE-DNA by Hsc70, DnaJB1 and ATP with similar rates as Hsf1wt. Fluorescence polarization assays containing Alexa Fluor® 488-HSE-DNA bound Hsf1(1-408) trimers and the indicated components.",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "A The rate of Hsc70/DnaJB1-mediated dissociation of HSE-DNA bound Hsf1 depends on the number of HR-B proximal Hsc70 binding sites in the Hsf1 trimer. Hsf1wt (wt) and Hsf1∆(202-213) (∆) monomers were mixed in the indicated ratios and heat shocked at 42°C for 10 min to form mixtures of different homo- and heterotrimers as indicated with the cartoons (the red line and the arrow head indicate the Hsc70 binding site). Numbers indicate the relative fraction of the different species.",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "B Moving the Hsc70 binding site away from the trimerization domain reduces the rate of Hsc70/DnaJB1-mediated dissociation of HSE-DNA-bound Hsf1. Hsf1_t10/20/30, region 202-213 moved by 10, 20, or 30 residues towards the C-terminus.",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "C Anti-FLAG antibodies are not able to dissociate HSE-DNA-bound Hsf1. Red lines in the cartoon indicate the Hsc70 binding site; blue lines and arrow head indicate the inserted FLAG epitope DYKDDDDK. Hsf1_i201/211/221, FLAG-epitope inserted after residue 201, 211 or 221. Anti-FLAG antibodies were split in halfmers by incubation with 2 mM DTT",
    "ncbi_link": "FLAG: 
Hsf1: 3297"
  },
  {
    "caption": "Anti-FLAG antibody halfmers bound to FLAG-epitope containing Hsf1 variants. Hsf1wt and FLAG-insertion variants were analyzed by blue-native gel electrophoresis in the absence or presence of DTT-treated anti-FLAG antibodies as indicated and Hsf1 detected by immunoblotting; t-bound, FLAG antibody-bound Hsf1 trimers; m-bound, FLAG antibody bound Hsf1 monomer.",
    "ncbi_link": "FLAG: 
Hsf1: 3297"
  },
  {
    "caption": "F Trimer-to-monomer ratio of freshly purified Hsf1wt and Hsf1-I190S,I194S in the absence of heat shock, determined by gel filtration and BN-Gel",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "G Rate of Hsc70/DnaJB1-mediated dissociation of HSE-DNA bound Hsf1wt and Hsf1-I190S,I194S",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "A Schematics of the used system. MEFs, in which HSF1 on chromosome 8 was deleted, were stably transfected with mTag-BFP expressed under the control of the HSPA6 promoter and subsequently transiently transfected with plasmids that expressed HSF1wt or mutant variants in an artificial operon with hrGFP, which is translated from an IRES element. B Exemplary flow cytometry data plotting BFP fluorescence versus GFP fluorescence, indicating the gates used for analysis. Numbers indicate the fraction (%) of cells (forward scatter singlets) in each gate. Color indicates the cell density from dark blue (low) to red (high).",
    "ncbi_link": "BFP: 
GFP: 
mTag: 
HSF1: 15499
HSF1: 3297
HSPA6: 3310"
  },
  {
    "caption": "C-H Geometric mean of BFP (C, E) and GFP fluorescence (D, F, H) of cells grown at 37°C (non-stress, NS) or incubated for 1 h at 43°C with a recovery period of 3 h at 37°C (heat shocked, HS) in the GFPhigh (C, D), GFPlow (E, F), and GFPlow-BFPhigh (H) gates. (G) Geometric mean of BFP fluorescence weighted by the relative number of cells in the GFPlow-BFPhigh gate (fluorescence * fraction forward scatter singlets). Note that the GFPlow gate also comprises the GFPlow-BFPhigh gate. Hsf1-202SSS, Hsf1-I202S,L203S,V205S; Hsf1-209SSS, Hsf1-I209S,L211S,L213S; Hsf1-427SSSS, Hsf1-M427S,L429S,L432S,L436S; Hsf1-465SSS, Hsf1-L465S,V466S,Y468S; Hsf1-473SSSS, Hsf1-L473S,F474S,L475S,L476S",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "A Schematics of the used system. HeLa cells were stably transfected with mTag-BFP expressed under the control of the HSPA6 promoter and subsequently transiently transfected with plasmids that expressed HSF1wt or mutant variants in an artificial operon with hrGFP, which is translated from an IRES element. Exemplary flow cytometry data plotting BFP fluorescence versus GFP fluorescence, indicating the gates used for analysis. Numbers indicate the fraction (%) of cells (forward scatter singlets) in each gate. Color indicates the cell density from dark blue (low) to red (high). NS, cells grown at 37°C; HS, cells heat shocked at 43°C for 1 h with a recovery period of 3 h at 37°C.",
    "ncbi_link": "BFP: 
GFP: 
mTag: 
HSF1: 3297
HSPA6: 3310"
  },
  {
    "caption": "C-H Geometric mean of BFP (C, E) and GFP fluorescence (D, F, H) in the GFPhigh (C, D), GFPlow (E, F), and GFPlow-BFPhigh43 (H) gates. Of note, the number of data points show the number of experiments in which a significant number of cells was found in this gate and missing bars indicate that cells did not fall within this gate in more than two out of four experiments. (G) Geometric mean of BFP fluorescence weighted by the relative number of cells in the GFPlow-BFPhigh43 gate (fluorescence * fraction forward scatter singlets). Note that the GFPlow gate also comprises the GFPlow-BFPhigh37 and that the GFPlow-BFPhigh37 gate also comprises the GFPlow-BFPhigh43 gate. Hsf1-202SSS, Hsf1-I202S,L203S,V205S; Hsf1-209SSS, Hsf1-I209S,L211S,L213S; Hsf1-427SSSS, Hsf1-M427S,L429S,L432S,L436S; Hsf1-465SSS, Hsf1-L465S,V466S,Y468S; Hsf1-473SSSS, Hsf1-L473S,F474S,L475S,L476S",
    "ncbi_link": "Hsf1: 3297"
  },
  {
    "caption": "Figure 4. Decrease of nucleoid number without mtDNA depletion in HeLa cells overexpressing the CHCHD10S59L and CHCHD10P34S alleles. A. Transfections were performed with empty vector (EV) or vectors encoding wild-type CHCHD10-FLAG (WT), CHCHD10-FLAG (S59L) or CHCHD10-FLAG (P34S) mutants. Mitochondria were stained with Mitotracker. Cells overexpressing wild-type and mutant CHCHD10 were labeled with FLAG antibodies. Nucleoids were visualized with an antiserum against DNA. Image analysis was performed by confocal microscopy. Scale bar: 10 µm.",
    "ncbi_link": "CHCHD10: 400916"
  },
  {
    "caption": "Figure 7. CHCHD10 mutant fibroblasts are less sensitive to apoptotic cell death compared to control fibroblasts. A. Control (C1, C2) and patient (P1, P2) fibroblasts were treated with 1 μM of staurosporine (STS) for 16 h. Cell death was determined by flow cytometry using Annexin V/DAPI staining. Three independent experiments were performed per condition with two points analyzed per experiment. Differences between the control and patient fibroblasts were analyzed by Student's t-test (two-sided): significant (*: p=0.0116) or extremely significant (***: p=0.0001).",
    "ncbi_link": "CHCHD10: 400916"
  },
  {
    "caption": "Figure 8. Overexpression of the CHCHD10 mutant alleles in HeLa cells leads to inhibition of apoptotic cell death. Transfections were performed with empty vector (EV) or vectors encoding either wild-type CHCHD10-FLAG (WT) or mutant CHCHD10-FLAG (P34S and S59L). A. Western blot on HeLa cells extracts using antibodies against FLAG or Hsp90.",
    "ncbi_link": "CHCHD10: 400916"
  },
  {
    "caption": "B-D. HeLa cells transiently expressing the WT or mutated forms of CHCHD10-FLAG (P34S or S59L) were treated with 1 μM Actinomycine D (ActD) for 4, 6 or 8 h with measurement of Annexin V/DAPI staining (B), DEVD-ase activity (C) from three independent experiments. Differences between the mutated and non mutated alleles were analyzed by Student's t-test (two-sided): significant (*:0.05>p>0.01) or very significant (**:0.01>p>0.001). P34S versus WT: **: p=0.0055 (4h), *: p=0.0103 (8h). S59L versus WT: *: p=0.0304 (4h), *: p=0.0129 (8h).",
    "ncbi_link": "CHCHD10: 400916"
  },
  {
    "caption": " H) Epifluorescence microscopy images of the prApe1-GFP/Atg19-mCherry/ypt7Δ, prApe1-GFP/Atg19Δ/ypt7Δ S. cerevisiae cells that were used to analyze the fluorescence intensity of all prApe1-GFP spots. BF represents bright-field images. ",
    "ncbi_link": "ypt7: 855012"
  },
  {
    "caption": " I) Bar plot showing the ratio between the GFP intensity of prApe1 spots in prApe1-GFP/Atg19-mCherry/ypt7Δ versus prApe1-GFP/Atg19Δ/ypt7Δ S. cerevisiae cells. The intensity of Ape1-GFP was normalized over the average fluorescence intensity of Nuf2-GFP measured in kinetochores as performed in [36]. Data information: a total of 54 prApe1-GFP spots and 80 Nuf2-GFP spots were analyzed in prApe1-GFP/Atg19Δ/ypt7Δ cells, whereas 52 prApe1-GFP spots and 98 Nuf2-GFP spots were analyzed in prApe1-GFP/Atg19-mCherry/ypt7Δ control cells. Error bars indicate standard error of the mean (SEM). *P = 0.03 (Z test). ",
    "ncbi_link": "Atg19: 854072
ypt7: 855012"
  },
  {
    "caption": " Figure 4: Quantification of the Ape1, Ams1, Atg19 protein abundances in living cells. (A) Epifluorescence microscopy images of the prApe1-GFP/Atg19-mCherry/ypt7Δ, Ams1-GFP/Atg19-mCherry/ypt7Δ, Atg19-GFP/Ape1-mCherry/ypt7Δ S. cerevisiae cells that were used to quantify the fluorescence intensity of GFP spots. Only co-localizing GFP and RFP spots were considered. BF represents bright-field images. (B) Bar plot showing the number of molecules of prApe1, Ams1 and Atg19 found in Cvt vesicles in living cells. Data information: data are representative of two independent experiments in which a total of 217 prApe1-GFP, 181 Ams1-GFP and 233 Atg19-GFP spots were analyzed. Error bars indicate standard deviation (SD). ***P < 0.001; *P = 0.0176 (Z test). ",
    "ncbi_link": "Ams1: 852721
Ape1: 853758
Atg19: 854072
ypt7: 855012"
  },
  {
    "caption": " (A) Fluorescence microscopy image of a resin section of prApe1-GFP/Atg19-mCherry/ypt7Δ cells, merge of green (prApe1-GFP) and red (Atg19-mcherry) channels. Tetraspeck beads are detected in the blue channel. (B) Electron tomography slice of the boxed area in (A). The outer and inner dashed green circles of 160 and 60 nm radius represent estimated 50% and 90% localization accuracy, respectively. Insets show close-up views of a double (top) and single (bottom) membrane. Corresponding tomogram Movie EV2. (C) Plot of the x and y dimensions of the Cvt vesicles obtained from localization correlation. The average dimensions give rise to spheroids with an average ellipticity of 11 % (shown in dark grey). Both prApe1-GFP and prApe1-GFP/Atg19-mCherry datasets were included. The cases representing autophagosomes were excluded. ",
    "ncbi_link": "ypt7: 855012"
  },
  {
    "caption": "(e) The heatmap shows the expression of genes most strongly associated with SSTR2 expression within the pericytes (left color bar indicates significant correlation or anti-correlation).",
    "ncbi_link": "SSTR2: 6752"
  },
  {
    "caption": "(i) The bar graph shows the genes most strongly correlated with SSTR2 belonging to the GO category "transcription regulators". The dotted line marks a correlation coefficient of zero.",
    "ncbi_link": "SSTR2: 6752"
  },
  {
    "caption": "(c) Relative expression level of CRTAC1 across human organs.",
    "ncbi_link": "CRTAC1: 55118"
  },
  {
    "caption": "(d) The box plots illustrate differences in mRNA detection for CRTAC1 in alveolar epithelial cells from fibrosis patients compared to control samples across the three indicated patient cohorts (Chicago cohort: ILD n = 9, controls n = 8; Nashville cohort: ILD n = 20, controls n = 10; Munich cohort: ILD n = 3, controls n = 11).",
    "ncbi_link": "CRTAC1: 55118"
  },
  {
    "caption": "(e) Relative gene expression levels of CRTAC1 in GSE47460. Dots represent average expression in the tissue of individual patients. The line represents the mean, error bars show SD. CRTAC1 is significantly downregulated in ILD but not COPD patients",
    "ncbi_link": "CRTAC1: 55118"
  },
  {
    "caption": "(f) For each single cell cohort, the gene-gene correlations with CRTAC1 within the SFTPC+ AT-2 cells were calculated. The indicated genes were selected based on their common direction of correlation across cohorts.",
    "ncbi_link": "CRTAC1: 55118"
  },
  {
    "caption": "(h) The bar graph shows the gene categories most strongly correlated with CRTAC1 belonging to the GO category of "transcription regulators". The dotted line marks a correlation coefficient of zero.",
    "ncbi_link": "CRTAC1: 55118"
  },
  {
    "caption": "Figure 1. Identification of non-canonical p53 binding sites in human subtelomeres. (A and B) ChIP-seq tracks for p53 in camptothecin (CPT) treated or untreated HCT116 cells were aligned with RNAPII, CTCF, RAD21, and SMC1 for human chromosome18q (A) or 13q (B) subtelomeres. Position relative to the centromeric end of the terminal TTAGGG repeat tract are indicated in bp at the top. Subtelomeric DNA paralogy segment tracks, internal telomere-like sequence tracks (red CCCTAA), and annotated RefSeq gene tracks are indicated above the ChIP-seq tracks. (C) Alignment of human subtelomeric elements containing non-canonical p53 recognition sequences. The position of the RepeatMasker-defined LTR10c element is shown; also note the (TG)n microsatellite repeat adjacent to the p53 binding site. (D) Schematic organization of non-canonical p53 binding sites found in human subtelomeres.",
    "ncbi_link": "RNAPII: 
CTCF: 10664
RAD21: 5885
SMC1: 8243
p53: 7157"
  },
  {
    "caption": "Stress-induced p53 binding at human subtelomeres. (A) Western blot of HCT116 p53-/- and p53+/+ cells treated with DMSO (D) or 50 µM etoposide (E) for 24 hrs. Cell lysates were assayed for total p53, phospho-Ser15 p53 (p-p53), γH2AX, or GAPDH.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(B) ChIP-qPCR was assayed in HCT116 p53-/- or p53 +/+ cells treated with DMSO or etoposide as in panel A, and assayed by ChIP with antibodies to p53 (Ab6) or control IgG, followed by qPCR for p53 binding site in subtelomere 18q (top panel) or 13q (lower panel).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) HCT116 p53-/- and p53+/+ cells were cultured in DMEM with 10% FBS or Hank's buffered saline solution (HBSS) lacking FBS and then assayed by ChIP with either IgG control (grey) or two different p53-specific antibodies Ab6 (red) or FL(black). ChIP was assayed by qPCR with primers proximal to p53 binding sites at 18q, 13q, or p21 promoter.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": ". (D) Doxycyclin (Dox)-inducible p53 H1299 cells were treated without (-) or with (+) Dox in media containing 10% serum or in serum free HBSS, and then subject to ChIP assay with control IgG or p53-specific Ab6 antibody. ChIP DNA was assayed by qPCR using primers specific for p53 binding site at p21 (top panel), p53-negative control IGX1A (middle panel), or p21 positive control (lower panel). Error bars represent SD, and * indicates p value < .05. p-values were determined by Student t-test.",
    "ncbi_link": "IGX1A: 
p53: 7157"
  },
  {
    "caption": ". Transcriptional activity of subtelomeric p53-response elements. (A) Luciferase test constructs containing either empty test vector (top), p53-response elements from 18q subtelomere (middle) or MDM2 promoter (lower) were assayed in HCT p53-/- cells transfected with two independent preparations of empty vector or p53 WT expression vector.",
    "ncbi_link": "MDM2: 4193
p53: 7157"
  },
  {
    "caption": "(B) RT-qPCR measure of p21 (top panel) or PARD6G (lower panel) in HCT116 p53-/- or p53+/+ cells after treatment with DMSO or 50 µM etoposide.",
    "ncbi_link": "p21: 1026
PARD6G: 84552
p53: 7157"
  },
  {
    "caption": "(D) RT-qPCR analysis of TERRA transcripts from 18q using two independent primer sets pr1 (top panel) or pr2 (lower panel) from HCT116 p53+/+ cells cultured with serum (grey bars) or in HBSS lacking serum (black bars). Error bars represent SD and * indicates p value <.05 using student t-test comparing treated and untreated samples.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": ". p53-dependent cell viability and telomere protection in response to DNA damage. (A) Western blot of total p53, γH2AX, and GAPDH in HCT116 p53-/- or p53+/+ cells treated with 1 µM or 50 µM etoposide for 24 hrs.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "s. (B) Cell cycle analysis of HCT116 p53-/- or p53+/+ cells untreated or treated with 50 µM etoposide for 24 hrs. Cell cycle was determined by FACS analysis of propidium iodide stained cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) Cell clonal survival assay for HCT116 p53-/- or p53+/+ cells treated with DMSO or 1, 1.5 or 2 µM etoposide for 24 hr prior to replating.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "E) TIF assay for HCT116 p53+/+ or p53-/- cells treated with 1 µM etoposide for 3 hrs. Telomere DNA FISH with TelC probe (red), γH2AX (green), Dapi (blue).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) Quantification of TIF assay for % cells with > 4 TIFs per cell for p53+/+ (black) or p53-/- (red) cell.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "G) Telomere length assay showing p53-/- or p53+/+ cells treated with either DMS0, 1 or 50 µM etoposide. Ethidium bromide (EtBr) stained agarose gels (left panel), Southern blot hybridized with Tel C probe (middle panel) or with α Satellite DNA promote (right panel). Quantification of telomereDNA signal relative to invariant bands in α Sat. Error bars represent SD and * indicates p values <.05 determined by student t-test (TLA), or chi-square (TIF assay).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(H) Two-dimensional agarose gel analysis of telomeric DNA from HCT p53+/+ or or p53-/- treated with 50 µM etoposide for 24 hrs. Ethidium gel (top) and Southern blot probed with TelG probe (lower panel). Single stranded telomere DNA (red arrow) and recombination/ replication-associated structures (blue arrow) are indicated.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Figure 5. p53-dependent histone modification changes in response to DNA damage stress. HCT116p53-/- (left panels) or p53 +/+ (right panels) were treated with DMSO (black) or 50 µM etoposide (red) for 24 hrs and assayed by ChIP-qPCR at various locations relative to the TTAGGG repeats across the chromosome18qsubtelomere (panel A) or 13qsubtelomere (panel B) or for control regions (p21 promoter, GKN1/2, PARKIN) as indicated below. ChIP-qPCR for p53, H3K9Ac, H3K27Ac, γH2AX, or IgG control were quantified as % input. Error bars indicates SD and * indicates p value<.05 using student t-test comparing ChIP values in p53+/+ relative to p53-/- cells for specific primer pairs.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) Dot blot analysis of telomere repeat or Alu repeat DNA from p53+/+ or p53-/- HCT116 cells treated with DMSO or etoposide (ETP) (as described in panel A), that were subject to ChIP with antibodies to IgG, p53, γH2AX, TRF2, or TRF1. Quantitation of three independent ChIP-assays for TRF1 and TRF2 is shown in the panel to the right. (",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) HCT116 p53+/+ or p53-/- cells treated with 50 µM etoposide were assayed by Western blot with antibodies for p53, γH2AX, H3K9Ac, panH3, and GAPDH at times 0, 8, 16, or 24 hr post-treatment.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "C-D) RT-qPCR analysis for cells treated as shown in panel A. (C) RT-PCR for the p21 (top), or PARD6G mRNA (lower). (D) RT-PCR for primer pairs spanning subtelomere18q as indicated below. Lower panel shows the No-RT control for 18qsubtelomere primers. RT-qPCR was quantified as relative to Actin with error bars indicating SD and * indicating p value <.05 using student t-test comparing etoposide (24 hr) relative to untreated for specific primer pairs.",
    "ncbi_link": "Actin: 
p21: 1026
PARD6G: 84552"
  },
  {
    "caption": "(B) Western blot analysis of CRISPR deleted cell lines 18q WT and 18q Δp53 treated with DMSO (D) or 50 µM etoposide (E) for 24 hr. Blots were probed with pan-p53, phospho-p53, γH2AX, or GAPDH (as loading control)",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C-E) RT-qPCR for p21 (C), PARDG6 (D), or 18q subtelomeric RNA (E) in 18q WT or18q Δp53 treated with DMSO (black) or 50 μM etoposide (red) for 24 hr. (F) ChIP-qPCR assay for γH2AX at 18q subtelomere in 18q WT or 18q Δp53 treated as in panels B-E.",
    "ncbi_link": "p21: 1026
PARDG6: 84552
p53: 7157"
  },
  {
    "caption": "B NPCs differentiated into neurons by overexpressing Ngn2 (one representative experiment is shown). Two weeks after the infection differentiated NPC were positive for neuronal markers βIII-tubulin (Tuj1), Map2, NeuN and humannuclei (hNu) and synaptic markers, the voltage-gated Na+ channels (PanNav) and the vesicular glutamate transporter 1 (VGlut1).",
    "ncbi_link": "Ngn2: 63973"
  },
  {
    "caption": "B Representative images of ultrastructural analysis of fixed neurons examined with electron microscope. PANK2 panel represents PKAN neuronal cells overexpressing PANK2 protein. Scale bar 500nm. Mitochondrial size was measured at level of the larger diameter along the perpendicular axis for all the mitochondria in >30 field (200 mitochondria in total) for each sample (one-way ANOVA).",
    "ncbi_link": "PANK2: 80025"
  },
  {
    "caption": "A Representative images of neurons stained with the neuron specific anti-NCAM antibody, ROS sensible fluorescent probe DCF, and the nuclei dye Hoechst. Scale bar 20 μm. Plots of the DCF fluorescence signal from NCAM positive controls- and PKAN humanneurons, infected or not with Ngn2-PANK2-LV. Data presented as means + SEM of at least three independent experiments (One-way ANOVA).",
    "ncbi_link": "Ngn2: 63973"
  },
  {
    "caption": "mRNA and protein expression of CiTLR5a-HA   (D),  CiTLR5b-HA   (D), CiTLR5a-GFP  (E), and  CiTLR5b-GFP  (E) plasmids in FHM  cells were examined by  qRT-PCR (upper panel) with EF1α  gene as an internal control and by immunoblotting  (IB) (lower panel) with β-tubulin as a reference (n = 4). Data information: All data are presented as mean ± SD. The two-tailed Mann-Whitney U-test was used for (D) and (E). n represents biological replicates. ***P < 0.001.",
    "ncbi_link": "HA: 
TLR5a: 
TLR5b: 
EF1α: 120485211"
  },
  {
    "caption": "Lysates of FHM   cells overexpressing CiTLR5a   were respectively incubated with FlaA, FlaB, FlaC, at pH  5.0 or pH  7.4 for 1 h at 4 °C, mixed with HA  Ab-coupled beads or streptavidin agarose  beads for 2 h at 4 °C, then analyzed by immunoblotting  (IB) with anti-HA  or anti-His  antibodies.",
    "ncbi_link": "TLR5a: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing CiTLR5b  were respectively incubated with FlaA, FlaB, FlaC, at pH  5.0 or pH  7.4 for 1 h at 4 °C, mixed with HA  Ab-coupled beads or streptavidin agarose  beads for 2 h at 4 °C, then analyzed by immunoblotting  (IB) with anti-HA  or anti-His  antibodies.",
    "ncbi_link": "TLR5b: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing CiTLR5a and CiTLR5b were respectively incubated with biotin-poly(I:C), biotin-ssRNA  (1 μg/mL) at pH  5.0 or pH  7.4 for 1 h at 4 °C, mixed with HA  Ab-coupled beads for 2 h at 4 °C, then analyzed by immunoblotting  (IB) with anti-HA  antibodies.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "N, O CiUNC93B1-Myc  and CiTLR5a-HA  (M) or CiTLR5b-HA  (N) were transfected into FHM  cells. Co-IP and immunoblotting  were conducted to test the interactions  between CiUNC93B1-Myc  and CiTLR5a-HA  or CiTLR5b-HA.",
    "ncbi_link": "HA: 
Myc: 
TLR5a: 
TLR5b: 
UNC93B1: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing  CiTLR5a  and CiTLR5b   (including region deletants) were incubated with biotin-poly(I:C). Vector was used as a control. Pull-down  and immunoblotting  (IB) were performed.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "H-K Lysates of FHM  cells overexpressing  CiTLR5a  and CiTLR5b  site mutants were incubated with biotin-poly(I:C). Vector and wild type were used as controls. Pull-down and immunoblotting  were carried out (H, J). (I, K) Relative band intensity ratios of (H) and (J) were analyzed by ImageJ, respectively (n = 3). Data information: All data are presented as mean ± SD. The two-tailed Mann-Whitney U-test was used for (I), and (K). n represents biological replicates. *P < 0.05, **P < 0.01.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing CiTLR5a   or CiTLR5b  were respectively treated with Endo H  and analyzed by immunoblotting  (IB) with anti-HA  antibody.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing CiTLR5a or CiTLR5b  mutants were respectively incubated with biotin-poly(I:C) (I) Vector and wild type were used as controls. Pull-down and immunoblotting  assays were conducted (I, (J, Relative band intensity ratios of (I) were analyzed by ImageJ (n = 3). Data information: All data are presented as mean ± SD. The two-tailed Mann-Whitney U-test was used for (J), n represents biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing CiTLR5a or CiTLR5b  mutants were respectively incubated with FlaC  (K). Vector and wild type were used as controls. Pull-down and immunoblotting  assays were conducted K). L) Relative band intensity ratios of (K) were analyzed by ImageJ (n = 3). Data information: All data are presented as mean ± SD. The two-tailed Mann-Whitney U-test was used for (L). n represents biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001.",
    "ncbi_link": "TLR5a: 
TLR5b: "
  },
  {
    "caption": "Lysates of FHM  cells overexpressing LoTLR5 (A),  DrTLR5a (B), DrTLR5b  (B),  IpTLR5-1  (C),  IpTLR5-2 (C), IpTLR5S (C),  OmTLR5M (D), OmTLR5S (D), were respectively incubated with FlaC-His  (1 μg/mL) at pH  5.0 or pH  7.4. Complexes were pulled down  by Anti-GFP  antibody coupling beads and analyzed by immunoblotting  (IB) with anti-His  antibody.",
    "ncbi_link": "TLR5-2: 108275971
TLR5-1: 108275978
TLR5S: 100304981
TLR5: 102693268
TLR5S: 100135812
TLR5a: 403138
TLR5b: 403139
TLR5M: 100137014"
  },
  {
    "caption": "Lysates of FHM  cells overexpressing HsTLR5 (E) were respectively incubated with FlaC-His  (1 μg/mL) at pH 5.0 or pH  7.4. Complexes were  pulled down  by Anti-GFP  antibody coupling beads and analyzed by immunoblotting  (IB) with anti-His  antibody.",
    "ncbi_link": "TLR5: 7100"
  },
  {
    "caption": "Lysates of FHM  cells overexpressing LoTLR5 (F), DrTLR5a (G),  DrTLR5b (G),  IpTLR5-1 (H),  IpTLR5-2 (H), IpTLR5S (H), were respectively incubated with biotin-poly(I:C) (1 μg/mL) at pH  5.0 or pH 7.4. Complexes were pulled down by streptavidin  beads and analyzed via immunoblotting with anti-GFP  antibody.",
    "ncbi_link": "TLR5-2: 108275971
TLR5-1: 108275978
TLR5S: 100304981
TLR5: 102693268
TLR5a: 403138
TLR5b: 403139"
  },
  {
    "caption": "Lysates of FHM cells overexpressing OmTLR5M  (I), OmTLR5S (I), and HsTLR5 (J) were respectively incubated with biotin-poly(I:C) (1 μg/mL) at pH  5.0 or pH  7.4. Complexes were pulled down by streptavidin  beads and analyzed via immunoblotting  with anti-GFP  antibody.",
    "ncbi_link": "TLR5: 7100
TLR5S: 100135812
TLR5M: 100137014"
  },
  {
    "caption": "Lysates of FHM  cells overexpressing  DrTLR5a and DrTLR5b mutants were incubated with biotin-poly(I:C) and analyzed by immunoblotting  (N), and relative band intensity ratios were analyzed by ImageJ (O) (n = 3). Vector and wild type (WT) were used as controls. Data information: All data are presented as mean ± SD. The two-tailed Mann-Whitney U-test was used for (O). n represents biological replicates. *P < 0.05, **P < 0.01.",
    "ncbi_link": "TLR5a: 403138
TLR5b: 403139"
  },
  {
    "caption": "Representative femur sections from 8-day-old wild-type and Dnmt2−/− mice. The staining of perivascular cells (GLS, green) is strongly reduced in Dnmt2−/− bone marrow. Nuclei are counterstained with DAPI. Scale bar: 100 μm.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Quantitative analysis of capillary numbers. GLS-positive capillaries were counted in wild-type (wt) and Dnmt2−/− (D2-) mice, in three independent high-power fields (HPF) per mouse (n = 7).",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Representative FACS plots of wild-type and Dnmt2−/− BM stained for Lin− Sca1+ and cKit+ cells.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Quantification of bone marrow LSK cells in wild-type (three independent experiments, each with pooled BM samples from 4 to 6 mice) and Dnmt2−/−bone marrow (three independent experiments, each with pooled BM samples of 5-9 mice).",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Restoration of the LSK cell population in adult Dnmt2−/− mice. Frequencies of LSK cells were normalized to the frequencies of LSK cells from the bone marrow of wild-type littermates at the indicated age (2-3 independent experiments, each with pooled bone marrow samples from 3 to 9 mice).",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Increased LSK CD34− and reduced LSK CD34+cell populations in 8-day- and 1-year-old Dnmt2−/− mice compared to wild-type (two independent experiments, each with pooled bone marrow samples from 3-9 mice).",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "qPCR analysis of Dnmt2 mRNA expression in haematopoietic tissues, normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
Dnmt2: 13434"
  },
  {
    "caption": "Proliferation analysis of primary bone marrow suspension cells. Primary bone marrow suspension cells isolated from the femurs of 8-day-old mice were grown together with the attached stromal cells. Dnmt2−/− population doubling levels of three biological replicates, each plated three times, were calculated relative to wild-type culture.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Reduced replating abilities of primary Dnmt2−/−bone marrow cells in a myeloid colony formation assay. For primary (1°) colony formation, 1.25 × 104 total bone marrow cells were plated in semisolid medium allowing myeloid differentiation. For secondary (2°) colony formation, cells were harvested and 0.1% of primary colonies were replated into semisolid medium. Results are from two independent experiments analyzing 9 wild-type and 13 Dnmt2−/−mice in total.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Reduced secondary CFU-preB colony formation of Dnmt2−/− cells. Numbers of CFU-preB-cell colonies are indicated per 5 × 104 wild-type or Dnmt2−/− total bone marrow cells. 10% of primary colonies were replated into secondary CFU-preB assays.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Stable engraftment (upper panel) and multi-lineage reconstitution (lower panel) of wild-type and Dnmt2−/− bone marrow transplants. CD11b: macrophages; Ly6G: granulocytes; CD45R: B cells; CD3: T cells.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Dnmt2 expression after 3 days of mesenchymal cell differentiation.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Alizarin Red staining, indicating enhanced osteoblast differentiation of primary stromal cells from Dnmt2−/− mice. Scale bar: 50 μm. Quantification was performed with three biological replicates.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "qPCR analysis of the osteoblast markers Osterix and Osteocalcin.",
    "ncbi_link": "Osteocalcin: 12096
Osterix: 170574"
  },
  {
    "caption": "Oil Red O/hematoxylin staining, showing reduced adipocyte differentiation of primary stromal cells from Dnmt2−/− mice. Scale bar: 50 μm. Quantification was performed with three biological replicates.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "qPCR analysis of the adipocyte markers CEBp alpha and Glut4.",
    "ncbi_link": "CEBp alpha: 12606
Glut4: 20528"
  },
  {
    "caption": "Representative Northern blot showing tRNA(Gly) and tRNA(Asp) fragmentation in bone marrow from 8-day-old and adult mice. tRNA(Ser) was included as a Dnmt2 non-substrate tRNA, and 5S rRNA was included as a loading control.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "tRNA fragment coverage for the Dnmt2 substrates tRNA(Gly) and tRNA(Asp), and the non-substrate tRNA(Ser) in bone marrow, as determined by deep sequencing. Wild-type coverage is represented in red, and Dnmt2−/− coverage is indicated in blue. The plots illustrate the specific increase of 5′-halves from tRNA-Gly and 3′-halves from tRNA-Asp fragments in Dnmt2 mutants.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Analysis of protein synthesis by dynamic SILAC. The top 10% of proteins that are translated slower in Dnmt2−/− versus wild-type cells are indicated in orange. The top 10% of proteins that are translated faster in Dnmt2−/− versus wild-type cells are shown in blue. A change of >  twofold is indicated by the black lines.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Dimethyl-labeling analysis of 8-day-old mouse bone marrow tissue. Proteins that were down-regulated (< twofold change) in Dnmt2-deficient cells are indicated in red, and up-regulated proteins (> twofold change) are shown in green. Nestin and periostin are marked with arrows.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Correlation between protein and mRNA expression for differentially expressed proteins. Proteins that were down-regulated (< twofold change) in Dnmt2-deficient cells are indicated in red, and up-regulated proteins (> twofold change) are shown in green. The Pearson correlation coefficient is −0.03.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Representative staining of nestin and periostin in femur sections from 8-day-old wild-type and Dnmt2−/− mice. The anti-periostin staining is comparable in the periosteum of wild-type and Dnmt2−/− mice, but is reduced in the bone marrow cells (compare the highlighted areas). Scale bar: 100 μm. Nuclei are counterstained with DAPI (blue).",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "Quantitative differences in the length of the nestin-positive trabecular zone (upper panel) between wild-type (30 measurements, three mice) and Dnmt2−/− (21 measurements, two mice) and in bone periostin-positive marrow areas (lower panel) between wild-type (26 measurements, three mice) and Dnmt2−/− (45 measurements, three mice) in femur sections from 8-day-old mice. Data are presented as mean ± SD.",
    "ncbi_link": "Dnmt2: 13434"
  },
  {
    "caption": "(E) Immunoblot (IB) analysis of expression of IFT74, IFT81, RabL2B and α-tubulin in control (sgSafe) or IFT74 KO RPE cells stably expressing either empty vector, FLAG-IFT74, or FLAG-IFT74 T438R. Representative images from three experimental replicates are shown. The cells were grown to confluence (without serum starvation), lysed and analyzed by Immunoblot. Molecular weights (kDa) estimated from a protein marker are indicated. Red asterisk: endogenous IFT74; black asterisks: FLAG tagged IFT74.",
    "ncbi_link": "FLAG: 
IFT74: 80173"
  },
  {
    "caption": "(G-I) Box plots showing centrosomal signal intensity of FLAG (G), IFT81 (H), or RabL2 (I) in the cells described in (D) serum starved for 24 hours. The relative fluorescence signal intensity compared with the average of the control (IFT74 KO + FLAG-IFT74 WT for (G) and sgSafe + empty for (H) and (I)) are shown. Data are combined from three experimental replicates. Statistics obtained through nested one-way ANOVA with Šídák's multiple comparison test. (G) The number of mother centrioles analyzed in each sample per replicate are: 78, 77, 78 (sgSafe + empty); 102, 95, 101 (IFT74 KO + empty); 54, 77, 85 (IFT74 KO + FLAG-IFT74 WT); 49, 83, 99 (IFT74 KO + FLAG-IFT74 T438R), (H) The number of mother centrioles analyzed in each sample per replicate are: 93, 137, 138 (sgSafe + empty); 109, 133, 193 (IFT74 KO + empty); 62, 146, 131 (IFT74 KO + FLAG-IFT74 WT); 41, 143, 133 (IFT74 KO + FLAG-IFT74 T438R), (I) The number of mother centrioles analyzed in each sample per replicate are: 64, 101, 106 (sgSafe + empty); 84, 105, 129 (IFT74 KO + empty); 52, 96, 121 (IFT74 KO + FLAG-IFT74 WT); 73, 92, 102 (IFT74 KO + FLAG-IFT74 T438R).",
    "ncbi_link": "FLAG: 
IFT74: 80173"
  },
  {
    "caption": "(K) Box plots showing the quantification of number of IFT88 particles per cilium in the experiment described in (J). Data are combined from three experimental replicates: The number of cilia analyzed in each sample per replicate are: 20, 20, 18 (sgSafe + empty); 20, 20, 18 (IFT74 KO + WT); 20, 20, 19 (IFT74 KO + FLAG-IFT74 WT). The number of IFT particles in individual cells in each experiment are available from Figures S7A, D, and G. Statistics obtained through nested one-way ANOVA with Tukey's multiple comparison test.",
    "ncbi_link": "FLAG: 
IFT74: 80173"
  },
  {
    "caption": "Time-lapse fluorescence microscopy recordings showing localization and dynamics of the sfGFPTssM fusion protein in the parental (WT) and TssJ mutated strains (TssJ D97K). Individual images were taken every 60 seconds. The corresponding time of each micrograph is indicated in the lower right part of the image. Stable foci in the WT strain and less stable foci in the TssJ D97K strain are respectively indicated by white and blue arrowheads. Scale bars, 1 µm.",
    "ncbi_link": "TssJ: "
  },
  {
    "caption": "Fluorescence microscopy recordings showing sfGFPTssM foci in the parental (WT) and TssM mutated strains (TssM Q779C/N780C, TssM ∆777-783). TssM foci containing cells are indicated by arrowheads. Microscopy analyses were performed independently three times, each in technical triplicate, and a representative experiment is shown. Scale bars, 1 µm.",
    "ncbi_link": "TssM: "
  },
  {
    "caption": "Fluorescence microscopy recordings showing TssBsfGFP sheath in the parental (WT) and TssM mutated strains (TssM Q779C/N780C, TssM ∆777-783). Fluorescent sheath containing cells are indicated by arrowheads. Microscopy analyses were performed independently three times, each in technical triplicate, and a representative experiment is shown. Scale bars, 1 µm.",
    "ncbi_link": "TssM: "
  },
  {
    "caption": "(A) RT-qPCR quantification of relative miR-21-3p and miR-21-5p levels in mouse brain, heart, kidney and epidermis. N=4 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "miR-21-3p: 102466637///387140///102465212
miR-21-5p: 102465212///102466637///387140"
  },
  {
    "caption": "(B) Fluorescent miR-21-3p in situ hybridization (pink) in dorsal skin of acutely irradiated (Ac-UV) and non-irradiated (no UV) Ppard +/+ and -/- mice. E: epidermis; D: dermis; HF: hair follicle. Magnification bar: 100m",
    "ncbi_link": "miR-21-3p: 102466637///387140///102465212
Ppard: 19015"
  },
  {
    "caption": "(C) RT-qPCR quantification of relative pri-miR-21 and miR-21-3p levels in the epidermis (left and middle), and of relative miR-21-3p in the dermis (right) of acutely irradiated (Ac-UV; +) and non-irradiated (-) Ppard +/+ and -/- mice. Pri-miR-21: Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.022; miR-21-3p: Ppard +/+ no UV vs Ppard +/+ Ac-UV P = 0.017, Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.008. N=3-4 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "miR-21: 102465212///102466637///387140
miR-21-3p: 102465212///102466637///387140
Ppard: 19015"
  },
  {
    "caption": "(D) RT-qPCR quantification of relative miR-21-3p levels in total skin of chronically irradiated (Chr-UV; +) and non-irradiated (-) Ppard +/+ and -/- mice. miR-21-3p: Ppard +/+ no UV vs Ppard +/+ Chr-UV P = 0.008, Ppard +/+ Chr-UV vs Ppard -/- Chr-UV P = 0.002, ns: non significant. N=4 animals per groups, one representative experiment is shown out of two independent replicates.",
    "ncbi_link": "miR-21-3p: 102465212///102466637///387140
Ppard: 19015"
  },
  {
    "caption": "(E) RT-qPCR quantification of relative miR-21-3p level in the epidermis of Ppard +/+ and -/-mice, acutely irradiated (Ac-UV; +) or non-irradiated (-), treated with the PPAR/ antagonist GSK0660 (+) or vehicle (-), as indicated. miR-21-3p: Ppard +/+ no UV vs Ppard +/+ Ac-UV P = 0.005, Ppard +/+ Ac-UV vs Ppard +/+ Ac-UV/GSK0660 P = 0.04, N=5 (Ppard +/+) to 3 (Ppard -/-) animals per group. One representative experiment is shown out of two independent replicates",
    "ncbi_link": "miR-21-3p: 102465212///102466637///387140
Ppard: 19015"
  },
  {
    "caption": "(F) RT-qPCR quantification of relative miR-21-3p levels in HaCat cells treated with the PPAR/ agonists GW501516, GW0742 (+) or vehicle (-) as indicated. miR-21-3p: Veh vs GW501516 P = 4E-04, Veh vs GW0742 P = 2E-04. N=2-3 biological replicates, one representative experiment is shown out of two independent replicates.",
    "ncbi_link": "miR-21-3p: 406991
miR-21-3p: 406991///387140"
  },
  {
    "caption": "(A) RT-qPCR quantification of relative pri-miR-21 level in HaCaT human keratinocytes treated with the PPAR/ agonist GW0742 (+) or vehicle (-), with (+) or without (-) cycloheximide (Cyclo) as indicated. Pri-miR-21: Veh vs GW0742 P = 0.009. N=3 biological replicates, one representative experiment is shown out of two independent replicates.",
    "ncbi_link": "miR-21: 406991"
  },
  {
    "caption": "(B) RT-qPCR quantification of relative pri-miR-21, pre-miR-21, miR-21-5p and miR-21-3p levels in HaCaT cells treated for 24h with 2 or 5ng/ml of recombinant human TGFβ-1 (+) or vehicle (-) as indicated. Pri-miR-21: Veh vs TGF-1 5ng/ml P = 0.029; Pre-miR-21: Veh vs TGF-1 5ng/ml P = 0.001; miR-21-5p: Veh vs TGF-1 5ng/ml P = 0.002; miR-21-3p: Veh vs TGF-1 5ng/ml P = 1.7E-05. N=3 biological replicates, one representative experiment is shown out of two independent replicates .",
    "ncbi_link": "miR-21: 406991
miR-21-3p: 406991
miR-21-5p: 387140///102465212///102466637///406991"
  },
  {
    "caption": "(C) RT-qPCR quantification of pri-miR-21, pre-miR-21, miR-21-5p and miR-21-3p levels in HaCat cells treated for 24h with the PPAR/ agonist GW0742 (+), TGFβ receptor inhibitor SB431542 (+), or vehicle (-) as indicated. Pri-miR-21: GW0742 vs SB431542 P = 0.004, GW0742 vs GW0742/SB431542 P = 0.015; Pre-miR-21: Veh vs GW0742 P = 0.022, GW0742 vs SB431542 P = 0.036, GW0742 vs GW0742/SB431542 P = 0.024; miR-21-5p: GW0742 vs SB431542 P = 0.034, GW0742 vs GW0742/SB431542 P = 0.024; miR-21-3p: Veh vs GW0742 P = 0.036, GW0742 vs SB431542 P = 0.011, GW0742 vs GW0742/SB431542 P = 0.008. N=3 biological replicates, one representative experiment is shown out of two independent replicates.",
    "ncbi_link": "miR-21: 406991
miR-21-3p: 406991
miR-21-5p: 387140///102465212///102466637///406991"
  },
  {
    "caption": "(D) RT-qPCR quantification of relative Tgfb1 level in the epidermis of acutely irradiated (Ac-UV) and non-irradiated Ppard +/+ and -/- mice. Tgfb1: Ppard +/+ no UV vs Ac-UV P= 0.034, Ppard +/+ Ac-UV vs Ppard Ac-UV P= 0.030. N=2-3 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "Ppard: 19015
Tgfb1: 21803"
  },
  {
    "caption": "(E) RT-qPCR quantification of relative miR-21-5p and miR-21-3p levels in the skin of Ppard +/+ mice treated with the TGFβ receptor inhibitor SB431542 (+) or vehicle (-), with (+) or without (-) acute UV exposure (Ac-UV). miR-21-5p: no UV vs Ac-UV P = 0.038, Ac UV vs Ac UV/SB431542 P = 0.028; miR-21-3p: no UV vs Ac-UV P = 0.017; Ac-UV vs Ac-UV/SB431542 P = 0.035. N=3 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "miR-21-3p: 102466637///387140///102465212
miR-21-5p: 102466637///387140///102465212
Ppard: 19015"
  },
  {
    "caption": "(A) RT-qPCR quantification of relative SMAD7 expression level in the epidermis of acutely irradiated (Ac-UV; +) ex vivo biopsies of human normal skin. SMAD7: no UV vs Ac-UV P = 0.032. N=4 biological replicates, one representative experiment is shown out of three independent experiments performed with the skin of three different donors.",
    "ncbi_link": "SMAD7: 4092"
  },
  {
    "caption": "(B) Left panel: wild-type (WT SMAD7 3'UTR) and mutated (MUT SMAD7 3'UTR; *: mutated nucleotides) miR-21-3p binding sequences in the humanSMAD7 3'UTR. Right panel: Luciferase reporter assay with wild-type (WT SMAD7 3'UTR) or mutated (MUT SMAD7 3'UTR) SMAD7 3'UTR in HEK293 cells overexpressing miR-21-3p (miR-21-3p mimic) or a scrambled sequence (Control).",
    "ncbi_link": "Luciferase: 
miR-21-3p: 406991
SMAD7: 4092"
  },
  {
    "caption": "(C) Left panel: normalized expression data of SMAD7 mRNA obtained from genomic microarray analysis of human HaCaT cells treated with a miR-21-3p mimic (miR-21-3p mimic) or a scrambled sequence (control). N=3 biological replicates. Middle panel: western blot quantification of SMAD7 protein level (normalized to GAPDH protein level) in human HaCaT cells treated with a miR-21-3p mimic (miR-21-3p mimic) or a scrambled sequence (control). SMAD7: control vs miR-21-3p mimic P = 0.031. N=3 biological replicates, Right panel: western blot of SMAD7 and GAPDH proteins in human HaCaT cells treated with a miR-21-3p mimic (miR-21-3p mimic) or a scrambled sequence (control), N=3 biological replicates; one representative experiment is shown out of two independent replicates.",
    "ncbi_link": "miR-21-3p: 406991
SMAD7: 4092"
  },
  {
    "caption": "(D) Western blot of Smad7 from epidermis of acutely irradiated (Ac-UV; +) Ppard +/+ and -/- mice. Loading control: GAPDH.",
    "ncbi_link": "Ppard: 19015"
  },
  {
    "caption": "(E) RT-qPCR quantification of relative TGFB1, SERPINE1, p21, RUNX and SNAI2 levels in human HaCaT cells treated with a miR-21-3p mimic (miR-21-3p mimic) or a scrambled sequence (control) with (+) or without (-) treatment with 2ng/ml recombinant TGFβ-1. SERPINE1: TGF-1 2ng/ml control vs miR-21-3p mimic P = 0.004; p21: TGF-1 2ng/ml control vs miR-21-3p mimic P =0.03; RUNX: TGF-1 2ng/ml control vs miR-21-3p mimic P = 0.04. N=3 biological replicates.",
    "ncbi_link": "p21: 1026
miR-21-3p: 406991
RUNX: 864///860///861
SERPINE1: 5054
SNAI2: 6591
TGFB1: 7040"
  },
  {
    "caption": "(C) RT-qPCR analysis of IL6, IL1B, IL1RAP, PTGS2, CCL5, CXCL10 and CASP14 levels in HaCat cells transfected with a miR-21-3p mimic or a scrambled sequence (control). IL6: control vs miR-21-3p mimic P = 0.05; IL1B: control vs miR-21-3p mimic P = 0.005; IL1RAP: control vs miR-21-3p mimic P = 0.008; PTGS2: control vs miR-21-3p mimic P = 0.050; CCL5: control vs miR-21-3p mimic P = 0.001; CXCL10: control vs miR-21-3p mimic P = 0.012; CASP14: control vs miR-21-3p mimic P = 9E-05. N=3 biological replicates, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "CASP14: 23581
CCL5: 6352
CXCL10: 3627
IL1B: 3553
IL1RAP: 3556
IL6: 3569
miR-21-3p: 406991
PTGS2: 5743"
  },
  {
    "caption": "(A) RT-qPCR quantification of Il6, Il1b, Ptgs2 and Ccl5 levels in the epidermis of acutely irradiated (Ac-UV; +) and non-irradiated (-) Ppard +/+ and -/- mice. Il6: Ppard +/+ no UV vs Ac-UV P = 7E-04, Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.008; Il1b: Ppard +/+ no UV vs Ac-UV P = 0.010, Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.016, Ppard -/- no UV vs Ac-UV P = 0.015; Ptgs2: Ppard +/+ no UV vs Ac-UV P = 0.028, Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.028, Ppard -/- no UV vs Ac-UV P = 8E-04; Ccl5: Ppard +/+ no UV vs Ac-UV P = 0.002, Ppard +/+ Ac-UV vs Ppard -/- Ac-UV P = 0.014, Ppard -/- no UV vs Ac-UV P = 0.010; ns: non significant. N=4 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "Ccl5: 20304
Il1b: 16176
Il6: 16193
Ppard: 19015
Ptgs2: 19225"
  },
  {
    "caption": "(B) Left panel: Immunostaining for infiltrating F4/80-positive macrophages in acutely irradiated (Ac-UV) and non-irradiated (no UV) Ppard +/+ and -/- miceskin sections. Magnification bar: 200m. Right panel: RT-qPCR quantification of relative levels of the macrophage marker Emr1 mRNA in total skin of acutely irradiated (Ac-UV; +) and non-irradiated (-) Ppard +/+ and -/- mice. Emr: Ppard +/+ no UV vs Ac UV P = 0.034; Ppard +/+ Ac UV vs Ppard -/- Ac UV P = 0.033. N=4 animals per group, one representative experiment is shown out of three independent replicates.",
    "ncbi_link": "Emr1: 13733
Ppard: 19015"
  },
  {
    "caption": "(C) RT-qPCR quantification of relative levels of Il6, Il1b, Ptgs2 and Tnfa in mouseepidermis acutely irradiated (Ac-UV; +) and non-irradiated (-), treated with miR-21-3p inhibitor (+) or mismatched control (-) as indicated.",
    "ncbi_link": "Il1b: 16176
Il6: 16193
miR-21-3p: 102465212///102466637///387140
Ptgs2: 19225
Tnfa: 21926"
  },
  {
    "caption": "(A) RT-qPCR quantification of relative levels of pri-miR-21, pre-miR-21, miR-21-5p and miR-21-3p levels in healthy human skin and human squamous cell carcinomas (SCC). pri-miR-21 Healthy skin vs SCC P = 0.043; pre-miR-21 Healthy skin vs SCC P = 3E-05; miR-21-5p Healthy skin vs SCC P = 7E-05; miR-21-3p Healthy skin vs SCC P = 1.4E-06. ≥ 5 independent biopsies per condition.",
    "ncbi_link": "miR-21: 406991///102465212///102466637///387140
miR-21-3p: 406991///102465212///102466637///387140
miR-21-5p: 406991///102465212///102466637///387140"
  },
  {
    "caption": "(B) RT-qPCR quantification of relative levels of pri-miR-21, pre-miR-21, miR-21-5p and miR-21-3p levels in healthy human skin and humanpsoriasis lesions. pri-miR-21 Healthy skin vs Psoriasis P = 0.034; miR-21-5p Healthy skin vs Psoriasis P = 0.034; miR-21-3p Healthy skin vs Psoriasis P = 0.036; ns: non significant, ≥ 4 independent biopsies per condition.",
    "ncbi_link": "miR-21: 406991
miR-21-3p: 406991///102465212///102466637///387140
miR-21-5p: 406991///102465212///102466637///387140"
  },
  {
    "caption": "(C) RT-qPCR quantification of relative levels of IL6, IL1B, PTGS2 and TNFA levels in epidermis of abdominal healthy humanskin biopsies exposed to acute UV ex vivo, with or without topical treatment with miR-21-3p inhibitor (+) or mismatched control (-) as indicated. ns: not significant. IL6: no UV vs Ac-UV P = 0.036, Ac-UV vs Ac-UV/miR-21-3p inhibitor P = 0.019; IL1B: no UV vs Ac-UV P = 0.002, Ac-UV vs Ac-UV/miR-21-3p inhibitor P = 0.023; PTGS2: no UV vs Ac-UV P = 0.008, Ac-UV vs Ac-UV/miR-21-3p inhibitor P = 0.022; TNFA: no UV vs Ac-UV P = 0.032, ns = non significant. ≥ 7 replicates, a pool of three independent experiments performed with the skin of three different donors is shown.",
    "ncbi_link": "IL1B: 3553
IL6: 3569
miR-21-3p: 406991///102465212///102466637///387140
PTGS2: 5743
TNFA: 7124"
  },
  {
    "caption": "Western blot analysis showing increased RNF8 protein level in HeLa cells after siRNA-mediated p97 depletion under physiological conditions and after IR (10 Gy).   Graph represents the quantifications of (A) (***P<0.001; unpaired t-test, n=3, mean +SEM).   ",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "Western blot analysis showing increased RNF8 protein level in HEK293 cells after doxycycline-induced mild expression of the p97EQ variant under physiological conditions and after IR (10 Gy).   Graph represents the quantifications of (E) (**P<0.01, ****P<0.0001; unpaired t-test, n=4, mean +SEM).   ",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "Western blot analysis of CHX chase kinetics showing reduced RNF8 degradation rate in HEK293 cells after siRNA-mediated p97 depletion.   Graph represents the quantifications of (H) (***P<0.001, ****P<0.0001; two-way ANOVA, n=3, mean +SEM) and Western blot for efficacy of siRNA depletion of p97 (right).   ",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "Western blot analysis of Flag-RNF8 denaturing-IP in HEK293 cells showing K48-linked hyper-ubiquitination of RNF8 after siRNA-mediated p97 depletion.",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "Western blot analysis of Strep-p97 Co-IP in HEK293 cells showing increased RNF8 interaction with p97EQ variant as compared to p97WT under physiological conditions and after IR (10 Gy).   Graph represents the quantifications of (K) (*P<0.05; unpaired t-test, n=2, mean +SEM).   ",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "Western blot analysis of Flag-RNF8 denaturing-IP in HEK293 cells showing the ubiquitination pattern of RNF8-WT and RNF8-RING* variant, under siRNA-mediated luciferase (siLuc) or p97-depleted conditions (sip97).",
    "ncbi_link": "Luc: 
luciferase: 
RNF8: 9025
p97: 7415"
  },
  {
    "caption": "Western blot analysis of CHX chase kinetics in U2OS cells, comparing the degradation rate of Flag-RNF8-WT and Flag-RNF8-RING*. Endogenous RNF8 was depleted by shRNF8 targeting only endogenous RNF8.   Graph represents the quantifications of (E) (ns P>0.05, ****P<0.0001; two-way ANOVA, n=3, mean +SEM).   ",
    "ncbi_link": "Flag: 
RNF8: 9025"
  },
  {
    "caption": "Western blot analysis of Flag-ATX3 WT or Flag-ATX3 VBM* Co-IP in HEK293 cells showing interaction of ATX3 with p97, RNF8 and p97 core co-factors Npl4-Ufd1. (* represents unspecific bands).",
    "ncbi_link": "ATX3: 
Flag: 
ATX3: 4287"
  },
  {
    "caption": "Western blot analysis of Strep-p97EQ Co-IP in HEK293 cells, in presence or absence (CRISPR knockout; ∆ATX3) of ATX3, showing increased interaction of RNF8 with p97 in absence of ATX3, under physiological conditions and after IR (10 Gy).   Graph represents quantifications of (F) (*P<0.05, **P<0.01; unpaired t-test, n=3, mean +SEM).   ",
    "ncbi_link": "Strep: 
ATX3: 4287
p97: 7415"
  },
  {
    "caption": "Western blot analysis of CHX chase kinetics in HeLa cells showing accelerated endogenous RNF8 degradation in the soluble fraction (Cytosol and Nucleosol) of ∆ATX3 cell extract. Arrow represents the main RNF8 band and asterisks represents unspecific bands.   Graphs represent the quantifications of (A). RNF8 level at starting point (0h) was shown without equalisation (left). In order to nullify the difference in RNF8 level at starting point (0h), we equalised RNF8 level to 100% and then compared the degradation rate (right). (**P<0.01, ***P<0.001, ****P<0.0001; two-way ANOVA, n=2, mean +SEM).   ",
    "ncbi_link": "ATX3: 4287"
  },
  {
    "caption": "Western blot analysis of CHX chase showing the kinetics of endogenous RNF8 degradation in the soluble fraction (Cytosol and Nucleosol) of ATX3 knockdown HeLa cells. The degradation was completely blocked after simultaneous inhibition of proteasome (MG132, 10µM).",
    "ncbi_link": "ATX3: 4287"
  },
  {
    "caption": "Western blot analysis of Flag-RNF8 denaturing-IP in HEK293 cells showing RNF8 hyper-ubiquitination in siRNA-mediated p97 or ATX3-depleted conditions.",
    "ncbi_link": "Flag: 
ATX3: 4287
RNF8: 9025
p97: 7415"
  },
  {
    "caption": "Western blot analysis of Flag-RNF8 denaturing-IP in HeLa cells showing RNF8 hyper-ubiquitination in ∆ATX3 condition. RNF8 hyper-ubiquitination was suppressed by reintroduction of GFP-ATX3-WT but not with GFP-ATX3-C14A or GFP-ATX3-UIM*.",
    "ncbi_link": "Flag: 
GFP: 
ATX3: 4287
RNF8: 9025"
  },
  {
    "caption": "Western blot analysis of CHX chase showing accelerated degradation of RNF8 in soluble fraction (cytoplasm+nucleoplasm) of HeLa cells, expressing DOX-inducible GFP-ATX3-C14A variant as compared to GFP-ATX3-WT. Endogenous ATX3 was depleted with siRNA targeting 3'UTR region of ATXN3.   Graph represents the quantifications of (A). In order to nullify the difference in RNF8 level at starting point (0h), we equalised RNF8 level to 100% and then compared the degradation rate. RNF8 level at starting point (0h) was also shown without equalisation. (*P<0.05, **P<0.01; two-way ANOVA, n=2, mean +SEM).   ",
    "ncbi_link": "GFP: 
ATX3: 4287
ATXN3: 4287"
  },
  {
    "caption": "Western blot analysis of CHX chase showing accelerated degradation of RNF8 in soluble fraction (cytoplasm + nucleoplasm) of HeLa cells, expressing DOX-inducible ATX3-UIM* variant as compared to ATX3-WT. Endogenous ATX3 was depleted with siRNA ATX3_3'UTR.   Graph represents the quantifications of (C). In order to nullify the difference in RNF8 level at starting point (0h), we equalised RNF8 level to 100% and then compared the degradation rate. RNF8 level at starting point (0h) was also shown without equalisation. (ns P>0.05, *P<0.05, **P<0.01, ****P<0.0001; two-way ANOVA, n=2, mean +SEM).   ",
    "ncbi_link": "ATX3: 4287"
  },
  {
    "caption": "Western blot analysis showing endogenous RNF8 protein level in soluble fraction (Cytosol and Nucleosol) of HeLa cells under indicated conditions. RNF8 level was significantly reduced after siRNA mediated ATX3 depletion and then was significantly rescued by DOX-inducible expression of GFP-ATX3-WT but not with GFP-ATX3-VBM.   Graphs represent the quantifications of (E). (ns P>0.05, * P<0.05, **P<0.01; unpaired t-test, n=3, mean +SEM).   ",
    "ncbi_link": "GFP: 
ATX3: 4287"
  },
  {
    "caption": "Colony forming assay (CFA) showing the IR sensitivity of HeLa cells under siRNA-mediated p97 or ATX3-depleted conditions. (n=3, mean ±SD).   CFA showing the IR sensitivity of HeLa-WT cells compared to HeLa∆ATX3 cells. (n=3, mean ±SD).   ",
    "ncbi_link": "ATX3: 4287
p97: 7415"
  },
  {
    "caption": "CFA showing the rescue of cell survival in IR treated, ATX3-depleted (siRNA), HeLa cells, after DOX-inducible expression of ATX3-WT but not with ATX3-C14A or ATX3-UIM* variant. (ns P>0.05, **P<0.01, ****P<0.0001; two-way ANOVA, n=3, mean ±SD).   CFA showing the rescue of cell survival in IR treated, ATX3-depleted (siRNA), HeLa cells, after DOX-inducible expression of ATX3-WT but not with ATX3-VBM variant. (ns P>0.05, *P<0.05, ***P<0.001, ****P<0.0001; two-way ANOVA, n=3, mean ±SD).   ",
    "ncbi_link": "ATX3: 4287"
  },
  {
    "caption": "Representative IF micrographs in U2OS cells showing IRIF formation of GFP-RNF8-WT, 53BP1 and γH2AX (first panel) and GFP-RNF8-∆RING, 53BP1 and γH2AX (second panel) under indicated siRNA-depleted or p97-inhibited (CB5083) conditions. (Scale bar; 10µm).   Quantification of (F) for GFP-RNF8-WT. Graph represents the percentage of cells with increased GFP-RNF8-WT foci (white bars) or percentage of cells with >5 53BP1 foci (grey bars). (***P<0.001, ****P<0.0001; two-way ANOVA, n=2, mean +SEM, at least 100 nuclei per condition and experiment).   Quantification of (F) for GFP-RNF8-∆RING. Graph represents the percentage of cells with increased GFP-RNF8-∆RING foci (white bars) or percentage of cells with >5 53BP1 foci (grey bars). (ns P>0.05, *P<0.01, **P<0.01, ****P<0.0001; two-way ANOVA, n=2, mean +SEM, at least 100 nuclei per condition and experiment).   ",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "CFA showing the IR sensitivity of 53BP1-proficient and deficient MCF7 cells under indicated siRNA-depleted conditions. Data was collected from two individual experiments with triplicates. (ns P>0.05; two-way ANOVA, n=2, mean ±SEM).",
    "ncbi_link": "53BP1: "
  },
  {
    "caption": "CFA showing the IR sensitivity of BRCA2-proficient and deficient DLD1 cells under indicated siRNA-depleted conditions. Data was collected from two individual experiments with triplicates. (**P<0.01, ***P<0.001; two-way ANOVA, n=2, mean ±SEM).",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "CFA showing the rescue of cell survival in IR treated, ATX3-depleted (siRNA), HeLa cells, after co-depletion (siRNA) of RNF8. (ns P>0.05, *P<0.05, ****P<0.0001; two-way ANOVA, n=3, mean ±SEM).",
    "ncbi_link": "ATX3: 4287
RNF8: 9025"
  },
  {
    "caption": "A, B. A fraction of OTULIN is localized at mitochondria where it suppresses M1-linked ubiquitination. HEK293T cells were transfected with control or OTULIN siRNA. Cells were harvested 72 h (A) or 48 h (B) after transfection or 15 min after TNF treatment (25 ng/ml). Mitochondria were isolated by differential centrifugation and purified by ultracentrifugation using an OptiPrepTM density gradient. 38% (A) or 20% (B) of the mitochondrial fractions and 2% (A, B) of whole cell lysates were analyzed by immunoblotting using the antibodies indicated. For the detection of M1-linked ubiquitin chains, either the 1E3 (A) or the 1F11/3F5/Y102L (B) antibody was used.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "D. TNF-induced mitochondrial M1-ubiquitination does not occur in HOIP-deficient cells. Wildtype (WT) and HOIP-KO HAP cells were treated with TNF (25 ng/ml, 15 min) and analyzed as described in A.",
    "ncbi_link": "HOIP: 268749"
  },
  {
    "caption": "A, B. PINK1 is stabilized by TNF treatment. HEK293T cells were treated with TNF (25 ng/ml, 15 min) or CCCP (10 µM, 90 min) before harvesting or incubated with OTULIN-specific siRNA for 48 h (A). Purified mitochondrial fractions were analyzed by immunoblotting using the indicated antibodies. Quantification of PINK1-specific signals normalized to TIM23 is shown in the right panel. Data represent the mean values with standard deviations of 4 independent experiments. *p < 0.05. A two-tailed non-parametric Mann-Whitney U-test was used to analyze statistical significance. In (A), *unprocessed PINK1; **processed PINK1.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "D. Catalytically active HOIP ubiquitinates overexpressed PINK1. HEK293T cells were transfected with the plasmids indicated. After 24 h, the cells were harvested under denaturing conditions and PINK1 was immunoprecipitated via the V5 tag followed by immunoblotting against ubiquitin.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "E. Recombinant HOIP ubiquitinates PINK1 in vitro. V5-tagged-PINK1 immunoprecipitated from transiently transfected HEK293T cells via the V5 tag was incubated with recombinant mouse Ube1, UBE2L3, C-terminal HOIP and ubiquitin for in vitro ubiquitination. The samples were then analyzed by immunoblotting using V5 antibodies.",
    "ncbi_link": "V5: 
PINK1: 65018"
  },
  {
    "caption": "F. Endogenous PINK1 is modified with M1 ubiquitin chains after TNF treatment. HEK293T cells were treated with TNF (25 ng/ml, 15 min), then endogenous PINK1 was immunoprecipitated from mitochondrial fractions. Cells mildly overexpressing PINK1-V5 were also included (lanes 4, 5, 8), to make sure that the immunoreactive bands seen for endogenous PINK1 indeed correspond to PINK1. As a control for the presence of M1-linked ubiquitin chains, immunoprecipitated PINK1 was treated with recombinant OTULIN. As controls for the specificity of the immunoprecipitation, beads only (lanes 6 - 8) and beads plus IgG (lane 9) were included. The samples were analyzed by immunoblotting using antibodies against PINK1, M1-ubiquitin, and phosphorylated ubiquitin. For immunoprecipitation of overexpressed PINK1, only 50% of cells were used in comparison to the immunoprecipitation of endogenous PINK1.",
    "ncbi_link": "V5: 
OTULIN: 90268
PINK1: 65018"
  },
  {
    "caption": "A. PINK1 antagonizes OTULIN activity in cells. HEK293T cells expressing HOIP and HOIL-1L, were transfected with PINK1, WT OTULIN or the inactive OTULIN mutant W96A, as indicated. The cells were lysed 24 h later under denaturing conditions, and lysates were subjected to affinity purification using the Strep-tagged UBAN domain of NEMO to enrich proteins modified with M1-linked ubiquitin. Proteins affinity-purified by Strep-Tactin beads were immunoblotted against ubiquitin.",
    "ncbi_link": "OTULIN: 90268
PINK1: 65018"
  },
  {
    "caption": "B. Catalytically active PINK1 increases p-S65-ubiquitin at mitochondria. HEK293T cells were transfected with wildtype PINK1 or kinase-dead (K/D) PINK1. 48 h after transfection, the cells were treated with TNF (25 ng/ml, 15 min) and lysed. Purified mitochondrial fractions were analyzed by immunoblotting using antibodies against p-S65-ubiquitin, PINK1, and VDAC (loading control).",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "C. The TNF-induced increase in p-S65-ubiquitin is abolished in PINK1-deficient cells. HEK293T cells were transfected with control or PINK1-specific siRNA and treated with TNF (25 ng/ml, 15 min) or CCCP (10 µM, 90 min) 48 h after transfection. The whole cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "D. TNF-induced M1 ubiquitination is reduced in PINK1-deficient cells. WT and PINK1-KO MEFs were treated with TNF (25 ng/ml, 15 min) and then harvested. Purified mitochondrial fractions were subjected to affinity purification using the Strep-tagged UBAN domain, as described in A, followed by immunoblotting using M1-ubiquitin-specifc antibodies, Strep-Tactin conjugated to horse radish peroxidase (to control the UBAN pulldown efficiency), and TIM23 (input control). Quantification of the M1-ubiquitin-positive signal intensities is shown in the lower panel. Data represent the mean values with standard deviations of 3 independent experiments; n.s. not significant, ***p < 0.001. A two-way ANOVA test was used to analyze statistical significance.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "E. The fast anti-apoptotic effect of TNF is not affected by the NF-κΒ inhibitor IκΒα. SH-SY5Y cells were transiently transfected with the NF-κΒ super-repressor IᴋBα-2S or luciferase as a control. 24 h later, the cells were treated with STS (5 µM, 2 h) with or without a 15 min pretreatment with TNF (25 ng/ml). Cells were fixed and stained by antibodies against active caspase-3. Signal intensities were quantified by immunocytochemistry and fluorescence microscopy. Expression of IᴋBα-2S was tested by immunoblotting using antibodies against the HA tag. Data represent the standard deviation of three independent experiments; at least 300 cells were counted per experiment. *p < 0.05, **p < 0.01. Student's t-test, two-tailed, n=3.",
    "ncbi_link": "luciferase: 
IᴋBα: 4792
IκΒα: 4792"
  },
  {
    "caption": "F. The protective effect of TNF is dependent on HOIP expression. HeLa cells were transiently transfected with control or HOIP siRNA. 48 h after transfection, cells were treated with STS (1 μM, 1 h) with or without a 15 min TNF pretreatment (25 ng/ml) and then harvested. The cytosolic fractions were analyzed by immunoblotting using cytochrome c antibodies. HOIP silencing efficiency was analyzed in whole cell lysates using antibodies against HOIP. GAPDH and actin were immunoblotted as input controls.",
    "ncbi_link": "HOIP: 55072"
  },
  {
    "caption": "G. The protective effect of TNF is dependent on PINK1 expression. HeLa cells were transiently transfected with control or PINK1 siRNA and treated as described in F. The cytosolic fractions were analyzed by immunoblotting using cytochrome c and PINK1 antibodies. GAPDH was immunoblotted as input control.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "A. Nuclear translocation of p65 is impaired in cells silenced for PINK1 expression. SH-SY5Y cells were transfected with control or PINK1-specific siRNAs. For rescue experiments, cells were co-transfected with wildtype PINK1, PINK1Δ77, or kinase-dead PINK1-K/D. Two days after transfection the cells were treated with TNF (25 ng/ml, 25 min), fixed and stained with p65 antibodies. The fraction of cells showing nuclear translocation of p65 was determined for each condition. Data represent the mean ± SEM of 3 independent experiments. The experiment was performed in triplicates and more than 300 cells were quantified per experiment and condition.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "B. PINK1 phosphorylates ubiquitinated NEMO. HEK293T cells were co-transfected with V5-tagged wildtype PINK1 or kinase-dead PINK1-K/D and HA-tagged NEMO. One day after transfection the cells were lysed and subjected to immunoprecipitation using antibodies against HA. Precipitated proteins were then detected by immunoblotting using p-S65-ubiquitin antibodies. The input was immunoblotted for NEMO, PINK1, p-S65-ubiquitin, and GAPDH.",
    "ncbi_link": "HA: 
V5: 
NEMO: 8517
PINK1: 65018"
  },
  {
    "caption": "C. Linear ubiquitination of NEMO is reduced in PINK1-deficient cells. HEK293T cells were co-transfected with HA-NEMO and control or PINK1-specific siRNAs. 48 h after transfection the cells were lysed and subjected to immunoprecipitation using antibodies against HA. Precipitated proteins were then detected by immunoblotting using M1-ubiquitin antibodies. The input was immunoblotted for NEMO and actin. PINK1 silencing efficiency was determined by real-time RT-PCR. Bars represent mean± SD with three technical replicates.",
    "ncbi_link": "HA: 
NEMO: 8517
PINK1: 65018"
  },
  {
    "caption": "B. Nuclear p65 translocation upon TNF treatment is reduced cells silenced for Miro1/2 expression. HeLa cells were transfected with control or Miro1 and Miro2 siRNAs. 48 h later, cells were treated with TNF (25 ng/ml, 15 min), fixed and stained using antibodies against p65 and tubulin and DAPI. Images were segmented in a cytoplasmic and nuclear compartment and the fluorescence signal intensity ratio of p65 was measured using CellProfiler 4.2.1. Quantification is based on 3 biological replicates. Kruskal-Wallis test followed by Dunn's multiple comparison test, n=79-157, *p < 0.05.",
    "ncbi_link": "Miro1: 55288
Miro2: 89941"
  },
  {
    "caption": "H, I, J. TNF increases mitochondria-nucleus contact sites in a HOIP-dependent manner. Representative immunofluorescence images (H, I) and quantification (J) of mitochondria-nucleus contact sites in control or HOIP-silenced (HOIP siRNA) HeLa cells transfected with the SPLICSNU-MT probe treated with 25 ng/ml TNF or PBS for 15 minutes. Mitochondria and nuclei were stained as described in E and F.",
    "ncbi_link": "HOIP: 55072"
  },
  {
    "caption": "Separase interacts with γH2AX in DSB-containing G2 but not G1 cells. Transgenic Hek293 cells treated with Dox to induce expression of Myc-separase-WT and with OHT to induce nuclear accumulation of ER-AsiSI and infliction of DSBs were synchronized in G1- or G2-phase and analysed by IP-Western",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Separase interacts with γH2AX in DSB-containing G2 but not G1 cells. Transgenic Hek293 cells treated with Dox to induce expression of Myc-separase-WT and with OHT to induce nuclear accumulation of ER-AsiSI and infliction of DSBs were synchronized in G1- or G2-phase and analysed b IFM for γH2AX- and Myc-separase-positive foc The quantification of the IFM in (E) shows averages (bars) of 3 independent experiments (dots) counting ≥ 100 cells each",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Separase is required for proper HDR but dispensable for NHEJ. U2OS DR-GFP (HDR reporter) and U2OS EJ5-GFP (NHEJ reporter) cells were separase-depleted by RNAi (SEP-1) or control-treated with GL2 siRNA, transfected to express HA-tagged ER-I-SceI, and then supplemented with OHT in G2-phase to induce nuclear accumulation of the homing endonuclease. Ethanol-supplemented samples served as negative controls. Two days later, cells were subjected to immunoblotting (A",
    "ncbi_link": "SEP-1: 9700
separase: 9700"
  },
  {
    "caption": "Separase is required for proper HDR but dispensable for NHEJ. U2OS DR-GFP (HDR reporter) and U2OS EJ5-GFP (NHEJ reporter) cells were separase-depleted by RNAi (SEP-1) or control-treated with GL2 siRNA, transfected to express HA-tagged ER-I-SceI, and then supplemented with OHT in G2-phase to induce nuclear accumulation of the homing endonuclease. Ethanol-supplemented samples served as negative controls. Two days later, cells were subjected t flow cytometry to quantify the percentage of GFP positive cells (B The GFP quantification in (B) displays averages (bars) of 3 independent experiments (dots)",
    "ncbi_link": "SEP-1: 9700
separase: 9700"
  },
  {
    "caption": "Separase is required for proper HDR but dispensable for NHEJ. U2OS DR-GFP (HDR reporter) and U2OS EJ5-GFP (NHEJ reporter) cells were separase-depleted by RNAi (SEP-1) or control-treated with GL2 siRNA, transfected to express HA-tagged ER-I-SceI, and then supplemented with OHT in G2-phase to induce nuclear accumulation of the homing endonuclease. Ethanol-supplemented samples served as negative controls Two days later PI-stained cellular DNA (C)",
    "ncbi_link": "SEP-1: 9700
separase: 9700"
  },
  {
    "caption": "Co-depletion of Wapl and separase has a synergistic effect on HDR. U2OS DR-GFP cells were transfected with the indicated siRNAs, treated as in (A+B) and analysed by GFP-flow cytometry (D Shown in (D) are averages (bars) of 2-3 independent experiments (dots)",
    "ncbi_link": "separase: 9700
Wapl: 23063"
  },
  {
    "caption": "Co-depletio of Wapl and separase has a synergistic effect on HDR. U2OS DR-GFP cells were transfected with the indicated siRNAs, treated as in (A+B) and analysed b immunoblotting (E)",
    "ncbi_link": "separase: 9700
Wapl: 23063"
  },
  {
    "caption": "(A) Transgenic Hek293 cells constitutively expressing a separase sensor (cartoon below) and inducibly expressing Myc-separase were transiently transfected to express Flag-AsiSI-ER, Dox- and/or OHT-treated in G2-phase and analysed by (IP-)Western",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Ser1660 is phosphorylated in response to DNA damage and required for the interaction of separase with γH2AX. Hek293 cells were arrested in G2 phase by sequential thymidine- and RO-3306 treatment, DRB- (+) or mock treated (-), and then analysed as indicated Myc-separase-WT or -S1660A expressing cells were subjected to (IP-)Western using, amongst others, a pan-specific antibody against phosphorylated serine (A, pan-pS",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Ser1660 is phosphorylated in response to DNA damage and required for the interaction of separase with γH2AX. Hek293 cells were arrested in G2 phase by sequential thymidine- and RO-3306 treatment, DRB- (+) or mock treated (-), and then analysed as indicated Myc-separase-WT or -S1660A expressing cells were subjected to (IP-)Western using, amongst other a separase antibody specific for phosphorylated Ser1660 (B, pS1660)",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Ser1660 is phosphorylated in response to DNA damage and required for the interaction of separase with γH2AX. Hek293 cells were arrested in G2 phase by sequential thymidine- and RO-3306 treatment, DRB- (+) or mock treated (-), and then analysed as indicated (C) DNA damage-induced Ser1660 phosphorylation of endogenous separase is largely blocked by ATM inhibition. G2-enriched Hek293 cells were treated with KU-55933 (0.3 μM) and/or DRB and analyzed by (IP-)Western 12 h thereafter using the indicated antibodies",
    "ncbi_link": "ATM: 472"
  },
  {
    "caption": " (D) Preventing NES phosphorylation spoils nuclear localization of separase in response to DSBs. HeLaK cells expressing N-terminally NLS-eGFP-tagged separase variants were treated with DRB or carrier solvent (− DRB) for 4 h and then subjected to IFM using anti-γH2AX and anti-Nup153 to visualize sites of DNA damage and nuclear pore complexes, respectively. Transgenic separase was detected based on the eGFP autofluorescence. Note that due to their relatively high nuclear concentration co-localization of separase-WT and -S1660D with γH2AX-foci is not discernable. Scale bar = 5 μm ",
    "ncbi_link": "separase: "
  },
  {
    "caption": " (F) Arg-methylation of RG-repeats mediates recruitment of separase to DSB-containing chromatin. Myc-separase-WT or -KG expressing cells were treated with DRB as indicated and analysed by (IP-)Western and Coomassie staining ",
    "ncbi_link": "separase: "
  },
  {
    "caption": "(A) Persistence of γH2AX- and MDC1-positive foci in absence of NES-phosphorylation or RG-methylation of separase. Transfected Hek293T cells were siRNA- and Dox-treated to deplete endogenous separase and induce expression of the indicated, siRNA resistant Myc-tagged separase variants, respectively. Then, they were constitutively (− washout) or transiently exposed to DRB (+ washout) and finally quantitatively assessed by IFM for γH2AX- and MDC1-positive foci. Shown are averages (bars) of 3 independent experiments (dots) counting ≥ 100 cells each. Scale bar = 5 μm",
    "ncbi_link": "separase: 
separase: 9700"
  },
  {
    "caption": " (C) Recruitment of separase-WT and -S1660D but not separase-superNES, -S1660A, and -KG to DSBs. Cells from (A) were treated as indicated and analysed by IFM for co-localization of Myc-separase with γH2AX-foci. Scale bar = 5 μm ",
    "ncbi_link": "separase: "
  },
  {
    "caption": " (D) Interaction of separase-WT and -S1660D but not separase-superNES, -S1660A, and -KG with γH2AX. Cells from (A) were subjected to (IP-)Western analysis as indicated. Lanes that illustrate cellular levels of cyclin A2 and γH2AX after DRB-washout and those that analyse interaction of Myc-separase variants with γH2AX in presence of DRB are labeled by red arrows and blue arrow heads, respectively",
    "ncbi_link": "separase: "
  },
  {
    "caption": "Lys-1034 is a major target of DSB-induced sumoylation of separase. Hek293T cells expressin Myc-separase-WT or -K1034R (D) were DRB- or mock-treated and subjected t Myc-I Input samples and eluates were immunoblotted using the indicated antibodies",
    "ncbi_link": "separase: "
  },
  {
    "caption": " (F) Cells expressing the indicated separase variants were DRB- or mock-treated and then lysed. Lysates and chromatin pelleted therefrom were assessed by immunoblotting and Coomassie staining, as indicated. Note that the lanes shown in the upper panels, although not directly juxtaposed, nevertheless originate from the same gel ",
    "ncbi_link": "separase: "
  },
  {
    "caption": "(A, B) SEPARASE+/+ and SEPARASE+/- MEFs were constitutively (− washout) or transiently exposed to DRB (+ washout) and then analysed by IF for cells with γH2AX- and 53BP1-positive foci. Shown are averages (bars) of 3 independent experiments (dots) counting ≥ 100 cells each. Scale bar = 5 μm. (C) Cell lysates from one experiment in (A) were analysed by immunoblotting using the indicated antibodies ",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": "SEPARASE+/+ and SEPARASE+/- MEFs were treated with DRB (+) or carrier solvent (−) for the indicated times and then analysed by immunoblotting of total cell lysates (D",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": "SEPARASE+/+ and SEPARASE+/- MEFs were treated with DRB (+) or carrier solvent (−) for the indicated times and then analysed b IPs using anti-Rad21 or unspecific IgG (E). The lower right two lanes show in vitro-expressed mouse Rad21 treated with hyperactive (SA) separase or a protease-dead (PD) variant",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": "(A) Transformation susceptibility of primary MEFs. SEPARASE+/+ versus SEPARASE+/- MEFs were infected to express E1A and hRasV12 and then subjected to a colony formation assay. Shown are representative images (left) and the graphical representation of the number of transformed foci (right) from two independent experiments (bars = standard deviations)",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": " (B) Two-stage DMBA (initiation) plus TPA (promotion) skin carcinogenesis. The number and size of skin papillomas are plotted against time for each genotype: SEPARASE+/+ (n=8) versus SEPARASE+/- (n= 11) ",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": " (C) Representative hematoxylin- and eosin-stained sections from SEPARASE+/- biopsies. (i) glandular hyperplasia; (ii) benign papilloma; (iii) squamous cell carcinoma. Scale bars are 200 µm in (i) and 500 µm in (ii) and (iii). (D) Quantitative histological assessment of the DMBA-TPA skin cancerogenesis assay. Given are numbers of total, and corresponding percentage in brackets ",
    "ncbi_link": "SEPARASE: 105988"
  },
  {
    "caption": "A) Murine small intestines immunostained for the proliferation marker Ki67, apoptosis marker cleaved caspase 3 (Cas3), or YAP from 4 control (Yapfl/fl Tazfl/fl) and 4 YAP/TAZ double conditional knockout (Villin-CreERt Yapfl/fl Tazfl/fl) animals treated with tamoxifen. Tissues were harvested and analyzed at day 7 after first tamoxifen injection. Loss of YAP/TAZ leads to a moderate increase in apoptosis (Cas3+) in crypt base stem cells, quantified on the right, but no overall effect on the morphology of the small intestine. Arrows point to apoptotic cells. B) Murine large intestines immunostained for proliferation marker Ki67, apoptosis marker cleaved caspase 3 (Cas3), or YAP from control (Yapfl/fl Tazfl/fl) and YAP/TAZ double conditional knockout (Villin-CreERt Yapfl/fl Tazfl/fl) animals treated with tamoxifen. Tissues were harvested and analyzed at day 7 after first tamoxifen injection. Loss of YAP/TAZ leads to an increased number of apoptotic (Cas3+) cells within the transverse folds of the ascending colon.",
    "ncbi_link": "Cre: 2777477
ER: 2099
Taz: 66826
TAZ: 66826
Villin: 22349
Yap: 22601
YAP: 22601"
  },
  {
    "caption": "C) Murine small intestines immunostained for YAP or cleaved caspase 3 (Cas3) from control (Villin-CreERt) and YAP/TAZ double conditional knockout (Villin-CreERt Yapfl/fl Tazfl/fl) animals treated with tamoxifen. Tissues were harvested and analyzed at day 7 after first tamoxifen injection. Loss of YAP/TAZ leads to a mild increase in apoptosis (Cas3+) in crypt base stem cells, but no overall effect on the morphology of the small intestine. Arrows point to stem cells (YAP nuclear staining), while arrows point to apoptotic cells (Cas3 staining). N > 10 animals per genotype. D) Murine large intestines immunostained for YAP or cleaved caspase 3 (Cas3 ) from control (Villin-CreERt) and YAP/TAZ double conditional knockout (Villin-CreERt Yapfl/fl Tazfl/fl) animals treated with tamoxifen. Tissues were harvested and analyzed at day 7 after first tamoxifen injection. Loss of YAP/TAZ leads to increased apopotosis (Cas3+) and severe morphological defects in the transverse folds of the ascending colon, but does not affect morphology of the remaining colon regions. Quantitatively, 75% of n = 4 animals showed this severe phenotype.",
    "ncbi_link": "Cre: 2777477
ER: 2099
TAZ: 66826
Taz: 66826
Villin: 22349
YAP: 22601
Yap: 22601"
  },
  {
    "caption": "A) Murine small (top) and large (bottom) intestines isolated from control (Cre negative) Lats1flox/flox Lats2flox/flox animals and Villin-CreERt Lats1flox/flox Lats2flox/flox animals treated with tamoxifen to induce homozygous deletion of Lats1/2 (dKO). Immunostaining for YAP and Ki67 shows a gradient of YAP expression along the crypt-villus axis in controls, with nuclear YAP and Ki67 positive cells restricted to the crypt base (representative images from n=5 mice). Tamoxifen treated (3 days i.p.) Villin-CreERt Lats1flox/flox Lats2flox/flox double homozygous mouse intestines show an enlarged crypt compartment after 7 days with strongly nuclear YAP immunostaining in all epithelial cells and an expanded proliferative zone marked by Ki67 positive cells. Note the gradient of YAP expression levels is maintained along the crypt-villus axis (representative images from n=5 mice for each genotype). (Right) Immunostaining for the Paneth cell marker Lyz reveals loss of this marker from the crypt base. (Bottom right) Q-PCR analysis of Wnt pathway target genes reveals that Lats1/2 dKO causes a mild reduction in Lgr5 expression, with complete loss of Olfm4.",
    "ncbi_link": "Cre: 2777477
ER: 2099
Lats1: 16798
Lats2: 50523
Lgr5: 14160
Olfm4: 380924
Villin: 22349"
  },
  {
    "caption": "B) Axin2 mRNA expression was measured by RNAscope (red) and found to be increased in both intensity and uniformity of staining along the crypt-villus axis in Lats1/2 dKO after 3 days post i.p. injection (dpi) with tamoxifen to induce the homozygous deletion of Lats1 and Lats2. At 7dpi, Axin2 mRNA levels remain uniform along the crypt-villus axis in Lats1/2 dKO animals, although their total level has declined compared to 3dpi.",
    "ncbi_link": "Axin2: 12006
Lats1: 16798
Lats2: 50523"
  },
  {
    "caption": "D) Q-PCR analysis of YAP-TEAD and their target genes Ctgf and Cyr61 reveals that Lats1/2 dKO causes a strong induction of Ctgf and Cyr61 expression, as expected, as well as a strong induction of the common Wnt and YAP target gene CyclinD1.",
    "ncbi_link": "Cyr61: 16007
Ctgf: 14219
CyclinD1: 12443
Lats1: 16798"
  },
  {
    "caption": "B) RNAscope in situ hybridisation analysis of TEAD1/2/4 mRNA expression from control (Cre negative) Lats1flox/flox Lats2flox/flox animals and Villin-CreERt Lats1flox/flox Lats2flox/flox animals treated with tamoxifen to induce homozygous deletion of Lats1/2 (dKO). Tamoxifen treated (3 days i.p.) Villin-CreERt Lats1flox/flox Lats2flox/flox double homozygous mouse intestines show elevated expression of TEAD1 and TEAD4 in both the small intestine (top) and colon (bottom). Tissues were harvested and analyzed at day 7 after first tamoxifen injection. (n=5 animals for each genotype)",
    "ncbi_link": "Cre: 2777477
ER: 2099
Lats1: 16798
Lats2: 50523
TEAD1: 21676
TEAD4: 21679
Villin: 22349"
  },
  {
    "caption": "C) Q-PCR analysis reveals a progressive increase in the YAP-TEAD target gene Ctgf in Lats1/2 dKO intestines at 3-days and 7-days post i.p. injection with tamoxifen, as well as similarly increased TEAD1 and TEAD4 expression, confirming that TEAD1 and TEAD4 are YAP-responsive genes. Notably, Axin2 and TEAD2 exhibit a mild but progressive decline over 3 to 7 days after Lats1/2 deletion, consistent with Axin2 being a known Wnt-specific target gene, and with Wnt signalling remaining active in Lats1/2 dKO intestines.",
    "ncbi_link": "Axin2: 12006
Ctgf: 14219
Lats1: 16798
TEAD1: 21676
TEAD2: 21677
TEAD4: 21679"
  },
  {
    "caption": "A) RNAscope in situ hybridisation analysis of TEAD1/2/4 mRNA expression from control (wild-type) and ApcMin mutant tumours from the small intestine (top) and colon (bottom). All three genes were strongly induced within the ApcMin mutant tumours, with TEAD2 being most strongly induced in colon ApcMin tumours (n=3 animals with multiple tumours within the small and large intestines).",
    "ncbi_link": "Apc: 11789
TEAD1: 21676
TEAD2: 21677"
  },
  {
    "caption": "C) Wnt activation in Apc5 homozygous mutant organoids drives a drastic shift in organoid morphology from budding structures to cystic spheres and increases the YAP protein level. Scale bar is 250µm. n > 10 organoids in each experiment. Quantification of YAP protein levels from crypt and villus regions of control organoids as well as from the regions bounded by rectangles in Apc5 organoids are shown on the right, with statistical significance in an unpaired 2-tailed t-test.",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "A) Src family kinase inhibition via Dasatinib treatment in control organoids enforces YAP cytoplasmic localisation after 4h of treatment in organoids cultured for 3d. n > 10 organoids in each experiment. B) Quantification of the percentage of nuclear YAP cells per control crypt bud as shown in panel (A), error bars show 1 SD (**** p <0.0001). n > 10 organoids per condition (top). Quantification of the nuclear/cytoplasmic ratio of YAP per cell in Apc5 mutant organoids as shown in panel (C). n > 10 organoids per condition (bottom). Statistical analysis was performed with an unpaired student's t-test. C ",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "C) Src family kinase inhibition via Dasatinib or eCF506 treatment in Apc5 organoids causes relocalisation of YAP to the cytoplasm. n > 10 organoids in each experiment. Q-PCR analysis of the YAP-TEAD target gene Ctgf reveals a strong inhibition of mRNA expression upon treatment with eCF506 (relative expression, error bars = 1 SD). Statistical analysis was performed with an unpaired student's t-test.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "B) Control VillinCreERt mouse small intestine immunostained for YAP shows a gradient of expression with mostly cytoplasmic localisation. Irradiation with 14Gy of X-rays drives strong nuclear localisation of YAP along the entire crypt-villus axis. Deletion of Src within VillinCreERt Srcflox/flox intestines prevents YAP nuclear localisation and normal regeneration after 14Gy irradiation. Arrows point to villar cells with nuclear YAP localisation. Lower panels show high-mag views of a different example than those shown in upper panels.",
    "ncbi_link": "Cre: 2777477
ER: 2099
Src: 20779
Villin: 22349"
  },
  {
    "caption": "A) Control and irradiated murine small intestines analysed with RNAscope in situ hybridisation for Myc mRNA (black arrows point to mRNA granules in the control) and by immunostaining for Sox9 protein reveals an expansion in the expression domain of both genes. Nuclear localisation of beta-catenin is readily detectable after irradiation. n = 3 samples per condition, quantification shown in the insets, error bars = 1 SD. Statistical analysis was performed with an unpaired student's t-test. Similar results were obtained at 3dpi and 5dpi.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "B) Q-PCR analysis of YAP, TEADs and their target genes Ctgf and Cyr61 over a 4 days post irradiation time course at 12Gy. Note the strong upregulation of TEAD4, Ctgf, and Cyr61. In contrast, Axin2, TEAD2 and Sox9 mRNA expression levels are only moderately altered, confirming that Wnt signalling remains active upon irradiation-induced YAP-TEAD activation. n = 4 biological replicates per time point. Statistical analysis was performed with unpaired t-test compared to the control 0Gy condition, * p<0.05, ** p<0.01, ***p<0.001.",
    "ncbi_link": "Axin2: 12006
Cyr61: 16007
Ctgf: 14219
Sox9: 20682
TEAD2: 21677
TEAD4: 21679
YAP: 22601"
  },
  {
    "caption": "D) Q-PCR analysis of Wnt and YAP target gene expression in intestinal crypts isolated at 1 day after 12Gy irradiation. Note the inhibition of Axin2, Sox9, YAP, Ctgf, Cyr61, and TEAD family expression upon treatment with Porcupine inhibitor LGK974. The mild reduction of Sox9 mRNA expression by LGK974 at 1 day after irradiation (1dpi) becomes more pronounced at 3 days after irradiation (3dpi). n = 4 biological replicates per condition, statistical analysis was performed with Student's 2-tailed t-test, error bars = 1 SD, * p<0.05, ** p<0.01, ***p<0.001.",
    "ncbi_link": "Axin2: 12006
Cyr61: 16007
Ctgf: 14219
Sox9: 20682
YAP: 22601"
  },
  {
    "caption": "(e; HA-GluN2Bct-CTMm; P = 0.785 compared to control (white bar); F(4,35) = 0.432, 8 independent experiments from 8 separate cell cultures and transfections). Levels of cDAPK1 or wtDAPK1 cotransfected with pcDNA3.0 vector (0:1, white bar) represent the control values, arbitrarily set as 1. *P 0.05, **P 0.01, ***P 0.001, compared with the control; n.s., not significant. Bars represent relative means ± s.e.m. Full-length blots are presented in Supplementary Figure 9. Membranes reprobed for β-actin were used as loading controls. One-way ANOVA with Fisher least significant difference test.",
    "ncbi_link": "GluN2B: "
  },
  {
    "caption": "(b) Design and production of TAT-GluN2Bct-CTM and TAT-GluN2Bct peptides (left) using an E. coli expression system. Coomassie blue staining after SDS-PAGE assessed their purity (right); left lane, size marker.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(c) Bath application of TAT-GluN2Bct-CTM (200 μM; n = 9), but not TAT-GluN2Bct (200 μM; n = 6), knocked down activated DAPK1, and this was prevented by NH4Cl (20 mM; n = 5; one-way ANOVA; P 0.001, F(5,36) = 10.891) and dose- (d, doses in μM; n = 4; P 0.001; F(6,21) = 18.14) and time-dependent (e; P 0.001; F(8,44) = 12.074). (f) A single pretreatment of TAT-GluN2Bct-CTM (sing; 200 μM, 60 min before and during the 30-min NMDA stimulation) produced a transient reduction of DAPK1, returning to baseline within 7 h (n = 4; P = 0.888), and an additional dose of the peptide after NMDA washout resulted in a persistent decrease in DAPK1 up to 7 h (mult; n = 4; ΔΔP = 0.002). One-way ANOVA; P 0.001, F(4,15) = 10.389.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(g) Synthetic peptides TAT-GluN2B and TAT-GluN2BCTM.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(h) TAT-GluN2BCTM (25 μM; n = 5; P = 0.001), but not control TAT-GluN2B (25 μM; n = 4; P = 0.223), decreased native DAPK1, and this was prevented by NH4Cl (20 mM; n = 5; P = 0.302). One-way ANOVA, P 0.001, F(5,24) = 13.591. Relative levels of DAPK1 were normalized to those in the saline control group and compared to the saline control (white bar; *P 0.05, **P 0.01 and ***P 0.001) or NMDA-treated group (gray bar; ΔP 0.05, ΔΔP 0.01 and ΔΔΔP 0.001). Membranes reprobed for β-actin were used as a loading control. Bars represent relative means ± s.e.m. Sample sizes represent number of individual experiments. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(a) Top, the synthetic cell-penetrating α-synuclein targeting peptide TAT-βsynCTM and its control TAT-βsyn. Middle, immunoblots demonstrate that TAT-βsynCTM (25 μM; n = 5), but not the CTM-lacking control peptide TAT-βsyn (25 μM; n = 5), specifically decreased the targeted endogenous α-synuclein (one-way ANOVA, Tukey post hoc, P 0.001, F(3,16) = 12.435), without affecting the level of unrelated control protein PSD-95 at 4 h (bottom), and this reduction was prevented in the presence of NH4Cl (20 mM; n = 5). Sample sizes represent individual experiments from at least 3 separate primary cultures. (",
    "ncbi_link": "TAT: 
βsyn: "
  },
  {
    "caption": "(b) Bath application of 100 μM TAT-GluN2Bct-CTM (36.54 ± 7.1% of control; n = 8; P = 0.001), but not TAT-GluN2Bct (89.13 ± 10.78%; n = 7; P = 0.311), 60 min before and during H2O2 treatment (300 μM; 30 min) knocked down DAPK1 at 2 h after washout, and this effect was rescued by NH4Cl (20 mM; n = 8; **P = 0.003 to control; P = 0.106 to H2O2-treated). One-way ANOVA, F(4,34) = 11.628, P 0.001. Bars represent DAPK1 levels relative to saline control group. β-actin was used as a loading control.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(c) LDH assay revealed that H2O2 treatment (300 μM; 30 min) resulted in a significant increase in neuronal death 12 h after treatment (n = 8; 2.50 ± 0.12; P 0.001 to control), which was rescued by breaking down H2O2 with catalase (100 U in 10 μl phosphate-buffered saline; n = 4; 1.17 ± 0.02; P = 0.001 to H2O2 group). H2O2-induced neurotoxicity was significantly reduced by TAT-GluN2Bct-CTM (50 μM; applied 60 min before and maintained throughout the experiments; n = 9; 1.56 ± 0.08; P = 0.001 to H2O2 group), but not by TAT-GluN2Bct (50 μM; n = 9; 2.63 ± 0.10; P = 0.105 to H2O2 group) or the NMDAR antagonist APV (1 μM; n = 4; 2.16 ± 0.14; P = 0.169 to H2O2 group). NH4Cl abolished the neuroprotective effect of TAT-GluN2Bct-CTM (n = 4; 2.39 ± 0.27; P = 0.538 compared to H2O2 group). One-way ANOVA, P 0.001, F(6,41) = 26.842. ***,ΔΔΔP 0.001; bars represent relative mean values ± s.e.m. normalized to the saline control (white bar, arbitrarily set as 1). n represents individual experiments from at least 3 separate primary cultures. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "TAT: "
  },
  {
    "caption": "(d) Immunoblots demonstrated specific DAPK1 knockdown in the infarct (Ipsi) but not contralateral (Contra) side following application of TAT-GluN2BCTM (10 mg per kilogram, i.v.; n = 3; t(4) = 14.459, P 0.001) but not TAT-GluN2B (10 mg per kilogram, i.v.; n = 3; t(4) = 0.739, P = 0.501). β-actin was used as a loading control; two-tailed Student's t-test ***P 0.001; n.s., not significant.",
    "ncbi_link": "GluN2B: 
TAT: "
  },
  {
    "caption": "(e) HE (left) and immunohistochemical DAPK1 (right) staining of adjacent brain sections. Compared with those in saline (top) and TAT-GluN2B-treated (middle) controls, TAT-GluN2BCTM treatment (bottom) selectively reduced infarct area (left) and DAPK1 levels (right) ipsilaterally. Black outlining delineates infarct areas as visualized with HE staining.",
    "ncbi_link": "GluN2B: 
TAT: "
  },
  {
    "caption": "(f) Left, brain sections stained with Fluorojade B in rats injected with saline (n = 6), TAT-GluN2B (n = 5) or TAT-GluN2BCTM (n = 5) after treatment as shown in a. Right, quantification of cellular damage by counting the number of Fluorojade B-positive cells in each 640 × 640 pixel image at 10× magnification. TAT-GluN2BCTM (10 mg per kilogram) displayed more prominent neuroprotection in the cortex (P 0.001) and striatum (P 0.001) as compared to TAT-GluN2B (10 mg per kilogram). Cortex: H(2) = 41.235; P 0.001; striatum: H(2) = 38.808; P 0.001. Kruskal-Wallis ANOVA on ranks with Dunn's post hoc; bars represent relative means ± s.e.m., ***,ΔΔΔP 0.001. n values represent tissue from 3 animals collected from at least 2 litters. Scale bars 1 mm in b,c,e, 20 μm in f. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "GluN2B: 
TAT: "
  },
  {
    "caption": "Relative expression  and co-localization  of IL6  mRNA and  IL-6  Signaling Scoring in integrated skin  cells by blended UMAPs.",
    "ncbi_link": "IL6: 16193
IL-6: 16193"
  },
  {
    "caption": "Quantification by real-time qPCR analysis of Il6  mRNA in the skin  of naïve and irradiated  (15Gy) WT mice  at indicated times, (n=3-6). Data information: Data represent mean ± SD (B, *P<0.05, **P<0.01, **P<0.01, ****P<0.001 by one-way ANOVA with Dunnet's multiple comparisons test (B), five independent experiments.",
    "ncbi_link": "Il6: 16193"
  },
  {
    "caption": "Quantification of ventral hair loss area 21 days post-IR   (15Gy) in WT and IL-6-/- mice, (n=11). Photographic images showing hair  loss  (area demarked by yellow dashed line) 21 days post-IR   (15 Gy) in wild type (WT) and IL-6-/- mice. Data information: Data represent mean ± SD C, *P<0.05, **P<0.01, **P<0.01, ****P<0.001 by , two-tailed Mann-Whitney test (C, ; five independent experiments.",
    "ncbi_link": "IL-6: 16193"
  },
  {
    "caption": "Histochemical  (H&E) and immunostaining  (red) showing skin morphology, and T cell  (CD3+) and neutrophil  (Ly6b+) infiltration in WT or IL-6-/- mice  before (naïve), and 14 days (H&E, Ly6b+), or 21 days (CD3+) post-IR. Infiltrating CD3+ T cells  (yellow arrows) within degenerating hair follicles (HF; dashed lines) are indicated. Scale bars, 100 μm. Quantification of epidermal  thickness at 14 days post-IR  (n = 5-8). Kinetics  of neutrophil  (Ly6b+) (n = 3-9) and  T cell (CD3+) (n = 3) infiltration. Data information: Data represent mean ± SD F, mean ± SD (G). *P<0.05, **P<0.01, **P<0.01, ****P<0.001 by two-tailed Mann-Whitney test F, or two-way ANOVA with Bonferroni's posthoc multiple comparisons test (G); five independent experiments.",
    "ncbi_link": "IL-6: 16193"
  },
  {
    "caption": "Quantification by  real-time qPCR analysis of Tnfa, Ccl3, and Ifng  mRNAs in whole skin  of WT and IL-6-/- mice  at indicated times  post-IR  (15Gy), (n = 5-7). Data information: Data represent mean ± SD H) *P<0.05, **P<0.01, **P<0.01, ****P<0.001 by , two-tailed Mann-Whitney test H), five independent experiments.",
    "ncbi_link": "Ccl3: 20302
Ifng: 15978
IL-6: 16193
Tnfa: 21926"
  },
  {
    "caption": "Western blot analysis shows phosphorylated STAT3  (p-Stat3), Akt  (p-Akt)), Erk1  and Erk2  (p-Erk1/2)), and β-Actin in the skin  of WT, IL-6-/-, and IL-1R-/- mice at indicated times  (days) post-IR  (15Gy).",
    "ncbi_link": "IL-1R: 16177
IL-6: 16193"
  },
  {
    "caption": "UMAP plots depicting relative expression   and localization  of Il1a  and Il1b  mRNAs in irradiated  and naïve skin-derived cell clusters.",
    "ncbi_link": "Il1a: 16175
Il1b: 16176"
  },
  {
    "caption": "Photographic images showing hair  loss 14 days post-IR   (15 Gy) in WT and IL-1R-/- mice. Quantification of ventral hair loss area 14 days post-IR   (15Gy) in WT and IL-1R-/- mice, (n = 4). Data information: Data represent mean ± SD. *P<0.05, by two-tailed Mann-Whitney test (C) five independent experiments.",
    "ncbi_link": "IL-1R: 16177"
  },
  {
    "caption": "UMAP plots depicting relative expression   and localization  of Ccr6  and Ccl20  mRNAs in irradiated  and naïve skin-derived cell clusters. Quantification by real-time qPCR analysis of Ccr6  and Ccl20  mRNAs in whole skin  of naïve and irradiated  (15Gy) WT and IL-6-/- mice  at indicated times  post-IR, (n=5-7). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by Mann-Whitney test Two independent experiments.",
    "ncbi_link": "Ccl20: 20297
Ccr6: 12458
IL-6: 16193"
  },
  {
    "caption": "Photographic images showing the development of radiodermatitis  and alopecia in irradiated  (15 Gy) WT and CCR6-/- mice at indicated times  post-IR. Escalating radiodermatitis, which manifests on day 7-10 as serous exudates  on the chin  and neck, is visible in both strains and progresses in WT mice  to alopecia  by day 14 post-IR  but resolves spontaneously in the CCR6-/- mice. Quantification (lower right) of the area of hair  loss at 14 days post-IR, (n = 6). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by Mann-Whitney test Two independent experiments.",
    "ncbi_link": "CCR6: 12458"
  },
  {
    "caption": "Histochemical staining  (H&E) and immunostaining  (red) show morphology  and infiltration of neutrophils  (Ly6b+) and T cells (CD3+) (red arrows) to the skin  and to the hair follicle (HF) (dashed lines) in WT or CCR6-/- mice  14 days post-IR. Scale bars, 50 μm (black) and 25 μm (red). Quantification of epidermal  thickness, neutrophils  (Ly6b+), total T cell  (CD3+) infiltration to the skin, and (F) CD3+ cells infiltration to the  hair follicle in (D), (n = 5-6). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by two-tailed Student's t test (E-Ly6b, by Mann-Whitney test Two independent experiments.",
    "ncbi_link": "CCR6: 12458"
  },
  {
    "caption": "Quantification by real-time qPCR analysis of Il6, Il17a, Ccl20, and Ccl3  mRNAs in the skin  of naïve WT and irradiated  (15Gy) WT and CCR6-/- mice  at 14 days post-IR, (n = 3-5). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by Mann-Whitney test Two independent experiments.",
    "ncbi_link": "Ccl20: 20297
Ccl3: 20302
CCR6: 12458
Il17a: 16171
Il6: 16193"
  },
  {
    "caption": "Quantification by  real-time qPCR analysis of Il6, Il17a, II22, Ccl3, Ccr6, and Ccl20  mRNAs in whole skin  of naïve and irradiated  (15Gy) control (PBS) and CSA  treated WT mice  at 14 days post-IR, (n = 5). Data information: Data represent mean ± SD. *P < 0.05, **P < 0.01 by two-tailed Mann-Whitney test; two independent experiments.",
    "ncbi_link": "Ccl20: 20297
Ccl3: 20302
Ccr6: 12458
Il17a: 16171
II22: 50929
Il6: 16193"
  },
  {
    "caption": "The shRNA targeting TAZ, but not YAP, knocked down the expression of the smaller protein (asterisk).",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "Exogenous TAZ/YAP was not processed proteolytically to cTAZ. RKO cells were transfected with the indicated plasmids expressing C-terminal HA-tagged TAZ or YAP.",
    "ncbi_link": "HA: 
TAZ: 
YAP: "
  },
  {
    "caption": "RKO, but not HEK293A cells, expressed both full-length TAZ and cTAZ transcripts. RT PCR primers targeting different regions",
    "ncbi_link": "cTAZ: 
TAZ: 6901"
  },
  {
    "caption": "Knock out of cTAZ in RKO cells using CRISPR/Cas9 technology. Monoclones (#3 and #14) were selected.",
    "ncbi_link": "CRISPR: 
cTAZ: 
Cas9: 901176"
  },
  {
    "caption": "Cluster analysis of RNA expression of WT, cTAZ-/-, and cTAZ-/- /GFP-cTAZ put-back RKO cells. Genes down- and up-regulated more than 2 folds (P < 0.05) in cTAZ KO cells were included in cluster analysis. Green and red indicate down- and up-regulated genes respectively.",
    "ncbi_link": "cTAZ: 
GFP: "
  },
  {
    "caption": "cTAZ suppressed expression of ISGs. RNA levels of selected ISGs in WT, cTAZ-/-, cTAZ-/-/GFP-cTAZ RKO cells were quantified by qPCR. Error bars indicate SD, n =3. **P<0.01; ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
GFP: "
  },
  {
    "caption": "cTAZ repressed 5×ISRE-luciferase activity induced by IFN-α. HEK293A cells were transfected with 5×ISRE-luciferase reporter along with the indicated plasmids, treated with or without IFN-α (50 ng/ml) for 12 hours. The expression of ectopic genes was determined by IB. Error bars indicate SD, n =3. ***P<0.001; one-way ANOVA test was used for statistical analysis.",
    "ncbi_link": "cTAZ: 
luciferase: "
  },
  {
    "caption": "Knockout of cTAZ promoted ISGs expression in the presence of IFN-α. WT and cTAZ-/- RKO cells were treated with or without of IFN-α (50 ng/ml) for indicated time, the expression of selected genes was quantified by qPCR. WT or cTAZ-/- group was normalized by basal level, respectively. Error bars indicate SD, n =3. *P<0.05; **P<0.01; Student's t-test.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "cTAZ attenuated heterodimerization between STAT1 and STAT2 induced by IFN-α. Following transfection, cells were treated with or without IFN-α (50 ng/ml) for 1 hour and subjected to IP assays using Flag antibody.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "Depletion of cTAZ enhanced the interaction between STAT1 and STAT2. RKO cell lines (WT and #14) were treated with IFN-α as in (B). IP assays were performed using STAT1 antibody.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "cTAZ attenuated interaction between STAT1 and importin α5 (Im-α5). Following transfection, HEK293A cells were stimulated using IFN-α IP assays were performed using Flag antibody.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "Deletion of cTAZ promoted nuclear accumulation of STAT1 upon IFN-α stimulation. RKO (WT and cTAZ-/-) cells treated with or without IFN-α (50 ng/ml) for 1 hour, fixed, and subjected to IF using STAT1 antibody (green). DNA was labeled by DAPI (blue). Scale bar, 50 μm. Quantification was performed using ImageJ software (right). N>C: nuclear; N=C: nuclear plus cytoplasmic; N<C: cytoplasmic localization.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "Deletion of cTAZ promoted nuclear accumulation of STAT1 upon IFN-α stimulation. Cells were treated and subjected to subcellular fractionation.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "cTAZ defective in STAT1-binding failed to block nuclear translocation of STAT1. HEK293A stably overexpressing STAT1 were transfected with the indicated plasmids, treated with or without IFN-α (50 ng/ml) for 1 hour, fixed, and subjected to IF Scale bar, 25 μm.",
    "ncbi_link": "cTAZ: 
STAT1: "
  },
  {
    "caption": "cTAZ repressed the antiviral activity of ectopic STAT1/2. HEK293A were transfected with indicated plasmids, infected with gVSV (MOI = 0.01) for 12 hours, fixed, and subjected to microscopy (Left). Viral infection and replication were marked by green fluorescence. Scale bar, 100 μm. (Right) Quantification of GFP positive cells. About 300 cells (from 3 different fields) were analyzed. Error bars indicate SD. **P<0.01; ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
GFP: 
STAT1: "
  },
  {
    "caption": "cTAZ effectively repressed antiviral activity of IFN-α. Transfection and infection were performed Top: GFP intensity of cell lysates was measured by a fluorometer. Bottom: viral GFP and ectopic cTAZ protein levels were detected by IB.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "Depletion of cTAZ repressed viral replication. RKO cell lines (WT and two independent cTAZ -/- clones) were infected with gVSV (MOI = 0.1) for 12 hours. Scale bar, 100 μm. The ratio of GFP positive cells were calculated About 300 cells (from 3 different fields) were analyzed. Error bars indicate SD. ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
GFP: "
  },
  {
    "caption": "Depletion of cTAZ repressed viral replication. Cells were treated GFP intensity of cell lysates was measured. Error bars indicate SD, n = 3. **P<0.01; ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
GFP: "
  },
  {
    "caption": "Depletion of cTAZ repressed viral replication. Cells were treated the viral genomic RNA was quantified by qPCR (normalized to human GAPDH). Error bars indicate SD, n = 3. ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
GAPDH: 2597"
  },
  {
    "caption": "cTAZ deficiency enhanced ISGs expression. Cells were treated the expression of IFIH1 and DDX58 were assessed by qPCR. Error bars indicate SD, n = 3. *P<0.05; **P<0.01; ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
DDX58: 23586
IFIH1: 64135"
  },
  {
    "caption": "Overexpression of cTAZ promotes virus infection. DOX-inducible cTAZ-overexpressing RKO cell lines were pre-treated with DOX for 48 hours (1 μg/ml). gVSV infection and GFP Fluorescence intensity quantification were performed Error bars indicate SD, n = 3. **P<0.01; ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "Overexpression of cTAZ repressed ISGs expression. Cells were treated the expression of IFIH1 and DDX58 were assessed by qPCR. Error bars indicate SD, n = 3. *P<0.05; **P<0.01; Student's t-test.",
    "ncbi_link": "cTAZ: 
DDX58: 23586
IFIH1: 64135"
  },
  {
    "caption": "IFN-α induced mRNA level of cTAZ. RKO cells were treated with different doses of IFN-α for 8 hours. RNA levels were measured by qPCR. Error bars indicate SD, n = 3. ***P<0.001; two-way ANOVA test was used for statistical analysis.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "STAT1/2 synergistically activated a cTAZ promoter. HEK293A cells were transfected with cTAZ reporter with or without STAT proteins. Promoter activity was determined using luciferase assay, and protein expression was determined by IB. Error bars indicate SD, n = 3. ***P<0.001; Student's t-test.",
    "ncbi_link": "cTAZ: 
luciferase: 
STAT1: "
  },
  {
    "caption": "STAT1/2 binding sites on cTAZ promoter. HEK293A were transfected with cTAZ promoters (wild type or mutants). Luciferase activity and responses to STAT1/2 expression were measured. Error bars indicate SD, n = 3. **P<0.01; Student's t-test.",
    "ncbi_link": "cTAZ: "
  },
  {
    "caption": "STAT1 occupied cTAZ promoter in an IFN-α-sensitive manner. RKO cells were treated with or without IFN-α (50 ng/ml) for 1 hour and subjected to ChIP assays. cTAZ PCR primers were designed to target STAT1/2 binding site. ISG15 promoter was included as a positive control.",
    "ncbi_link": "cTAZ: 
ISG15: 9636"
  },
  {
    "caption": "(B) DraI digestion of PCR products from the multiple organs of the four fetuses (Upper). NC, negative control with no genomic DNA loaded. Mut, MITFL247S/L247S genomic DNA loaded. WT, LW genomic DNA loaded. Multiple organs of the four fetuses were examined for KIT expression by agarose gel electrophoresis (Bottom). Mut, MITFL247S/L247S genomic DNA loaded. WT, LW genomic DNA loaded",
    "ncbi_link": "KIT: 396810
MITF: 414902"
  },
  {
    "caption": "(A) Representative microscopic appearances of the retina and RPE cells (arrowhead) of a chimeric, a WT and a Mut fetus at the same gestational age by H&E staining. WT, Bama WT fetus. Mut, Bama MITFL247S/L247S fetus. NW-2, the chimeric fetus. Scale bars, 100 μm",
    "ncbi_link": "MITF: 414902"
  },
  {
    "caption": "(B) Representative immunofluorescence images showed the expression of multiple RPE markers Pax6, MITF and Bestrophin in the chimeric fetuses. Blue, Hochst3342. WT, Bama WT fetus as positive control. NW-2, the chimeric fetus. MITFL247S/L247S fetus as negative control. Scale bars, 50 μm",
    "ncbi_link": "MITF: 414902"
  },
  {
    "caption": "(B) Digestion of the MITF PCR products in multiple organs of the full-term chimeric pig. NC, negative control with no genomic DNA loaded. Mut, MITFL247S/L247S genomic DNA loaded. WT, Bama GFP-labeled genomic DNA loaded. In the chimera piglet, GFP-specific primers were used to further confirm the chimeric contribution to multiple organs in the piglet. GAPDH was used to confirm the DNA quality of all the samples. NC, negative control with no genomic DNA loaded. Mut, Bama MITFL247S/L247S genomic DNA loaded. WT, Bama GFP-labeled genomic DNA loaded",
    "ncbi_link": "MITF: 414902"
  },
  {
    "caption": "(D) Representative immunofluorescence images showed the expression of a corneal epithelial cell marker (K12) in GFP-labeled cells. WT, Bama WT piglet. Mut, Bama MITFL247S/L247S piglet. CH, chimeric piglet. Scale bars, 50 μm",
    "ncbi_link": "MITF: 414902"
  },
  {
    "caption": "(B) Detection of WASH gene targeting. The floxed WASH gene by gene targeting was analysed by Southern blotting (left panel) and PCR (middle panel). The genotypes of the offspring were analysed by PCR (right panel).",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(C) WASH deficiency is embryonic lethal. E11.5 of WASH deficiency showed a shrinked decidua.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(D) Histology analysis of E7.5 WASH+/+ and WASH−/−embryos. Scale bar, 100 μm.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(E) WASH‐deficient embryos do not undergo apoptosis. TUNEL assay was performed for apoptosis detection. PI, propidium iodide. FITC, fluoresceinisothiocyanate. Scale bar, 100 μm.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(F) E7.5embryos of WASH−/−mice present extensive autophagy. Ultrastructure of isolated E7.5embryos was stained with antibody against LC3 and visualized by immuno‐electron microscopy. Black arrowhead indicates autophagosome. *, Cellular reference. Scale bar, 500 nm (upper panel). WASH+/+ or WASH−/−embryos were isolated, and LC3 conversion and p62 level were analysed by immunoblotting (lower panel). Bands were quantified and analysed by Image J and shown as means±s.d. ***P0.001. Above experiments were repeated for three independent times with similar results.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(A) WASH deficiency enhances autophagy induction. WASH+/+ or WASH−/− MEFs were treated with EBSS for the indicated times in the presence or absence of 20 nM bafilomycin A1 (BafA1), and harvested for immunoblotting. Ratios of LC3‐II/β‐actin were calculated and shown at the right panel.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(B) WASH knockout accelerates LC3 conversion by confocal microscopy. Endogenous LC3 puncta were visualized by staining with antibody against LC3 (left panel), and calculated as shown in the right panel. Nuclei were stained with DAPI. Scale bar, 10 μm.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(C) Poly‐ubiquitinated proteins are reduced in WASH−/− MEFs. WASH+/+ and WASH−/− MEFs were starved in EBSS for 2 h treated with or without 20 nM BafA1 or 10 μM MG132. Cells were harvested for immunoblotting with anti‐poly‐ubiquitin antibody (Enzo, clone FK1) that only recognizes poly‐ubiquitinated ubiquitin chains.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(D) Autophagosome‐like structures in WASH+/+ and WASH−/− MEFs were visualized after starvation for 1 h by immuno‐electron microscopy with antibody against LC3 (left panel). Black arrowhead indicates autophagosome. Scale bar, 500 nm. *, Cellular reference. Fifty cells were quantified from three independent experiments (right panel). Data were shown as means±s.d. *P0.05 and **P0.01. Experiments were repeated for three independent times with similar results.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(A) WASH colocalizes with GFP‐LC3 upon starvation. HeLa cells stably expressing GFP‐LC3 were stained with anti‐WASH antibody after treatment with EBSS or culture medium (CM) for 1 h.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) WASH deficiency enhances the interaction of Vps34 with Beclin 1. WASH+/+ and WASH−/− MEFs were treated with EBSS at 37°C for 1 h and immunoprecipitated for Beclin 1. IP, immunoprecipitation. Ratio of Vps34/Beclin 1 was calculated by the Image J software and shown in the right panel.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(B) WASH KO MEFs were treated with or without EBSS at 37°C for EBSS followed by kinase assays. Cells were lysed and incubated with anti‐Beclin 1 antibody to precipitate the autophagy‐related Vps34. Immunoprecipitates were separated into two equal parts, one for kinase assays and the other for input detection. RLU, relative light unit.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(C) WASH deficiency enhances Vps34 activity. WASH+/+ and WASH−/− MEFs stably expressing GFP‐WIPI1 were stimulated with or without EBSS for 1 h followed by confocal microscopy (left panel). GFP‐WIPI1 dots were calculated and shown in the right panel. Scale bar, 10 μm.",
    "ncbi_link": "WASH: 68767
WIPI1: 52639"
  },
  {
    "caption": "(D) WASH‐silenced HeLa cells were treated with or without EBSS at 37°C for 1 h, and detected as above.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "(E) WASH attenuates the interaction of Beclin 1 with Vps34. MEFs stably expressing vector or Flag-WASH were starved with EBSS for 1 h, followed by immunoprecipitation with anti‐Beclin 1 antibody. Ratio of Vps34/Beclin 1 was shown in the right panel.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(F) WASH overexpression reduces Vps34 activity. MEFs stably expressing GFP‐WIPI1 were transfected with vector or Flag-WASH and then starved with EBSS for 1 h, followed by visualization with confocal microscopy (upper panel). GFP‐WIPI1 dots were calculated and shown in the lower panel. Scale bar, 10 μm. Data are shown as means±s.d. **P0.01 and ***P0.001. Experiments were repeated for three independent times with similar results.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "WASH: 68767
WIPI1: 52639"
  },
  {
    "caption": "(A) The interaction of WASH with Beclin 1 was validated by yeast two‐hybrid assays. Yeast strain AH109 was co‐transfected with Gal4 DNA‐binding domain (BD) fused WASH and Gal4 activating domain (AD) fused Beclin 1. p53 and large T antigen or a known WASH interactor Bloc1s2 was introduced as positive controls.",
    "ncbi_link": "Gal4: 855828
WASH: 100287171"
  },
  {
    "caption": "(B, C) WASH co‐immunoprecipitates Beclin 1 in mammalian cells. Flag‐tagged Beclin 1 and Myc‐tagged WASH were co‐transfected into HEK293T cells and immunoprecipitations were performed at 24 h post transfection. IP, immunoprecipitation.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(E) The indicated Flag‐tagged Beclin 1 constructs encoding different regions of Beclin 1 were co‐transfected with full‐length HA‐tagged WASH (HA-WASH) into HEK293T cells followed by immunoprecipitation.",
    "ncbi_link": "Beclin 1: 56208"
  },
  {
    "caption": "(C) Lysine 437 mutation to arginine (K437R) abrogates ubiquitination of Beclin 1. Different constructs of Flag‐tagged Beclin 1 mutants were co‐transfected with HA‐tagged ubiquitin (HA-Ub) into HEK293T cells.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(D) Beclin 1 (WT) or K437R‐Beclin 1 (K437R) mutant was stably expressed in Beclin 1‐silenced HeLa cells. Beclin 1‐knockdown HeLa cells were infected with lentivirus encoding 3XFlag‐tagged WT Beclin 1 (WT) or K437R‐Beclin 1 (K437R).",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(E) K437R‐Beclin 1 mutant abrogates the enhanced interaction of Beclin 1 with Vps34 during autophagy. HeLa cells expressing 3XFlag-Beclin 1 or 3XFlag-K437R‐Beclin 1 were treated with EBSS for 1 h, and harvested for immunoprecipitation.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(F) Vps34 kinase activity is impaired by K437R‐Beclin 1 mutant. HeLa cells were transfected with the indicated vectors for 24 h and immunoprecipitated with anti‐HA antibody followed by a Vps34 kinase assay. Immunoprecipitates were separated into two equal parts, one for kinase assays and the other for input detection.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(G) K437R‐Beclin 1 reduces the activation of Vps34. Beclin 1‐silenced HeLa cells stably expressing GFP‐HeLa were rescued with WT‐ or K437R‐Beclin 1, followed by stimulation with 1 h for 1 h. GFP‐WIPI1 dots were visualized by confocal microscopy.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(H) K437R‐Beclin 1 mutant fails to induce autophagy after starvation. Beclin 1‐knockdown HeLa cells expressing WT or K437R mutant of Beclin 1 (K437R) were starved with EBSS for the indicated times.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(I) K437R‐Beclin 1 mutant suppresses autophagosome formation. Beclin 1‐knockdown HeLa cells expressing WT‐Beclin 1 or K437R‐Beclin 1 were infected with lentivirus encoding GFP‐LC3, and stimulated with EBSS for 1 h in the presence or absence of 20 nM BafA1. GFP‐LC3 dots were visualized by confocal microscopy. Scale bar, 10 μm. Data are shown as means±s.d. **P0.01 and ***P0.001. All the above experiments were repeated for at least three times with similar results.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(A) WASH overexpression suppresses the ubiquitination of Beclin 1. HEK293T cells were transfected with the indicated vectors for 24 h followed by an Ni‐NTA‐based pull‐down assay and immunoblotted with anti‐poly‐ubiquitin (anti‐poly‐Ub) (left panel), and anti‐K63‐specific ubiquitin (anti‐K63‐Ub) (middle panel) antibodies. The same blot was stripped and probed with anti‐K48‐specific ubiquitin (anti‐K48‐Ub) antibody (right panel).",
    "ncbi_link": "Beclin 1: 8678
WASH: 100287171"
  },
  {
    "caption": "(B) WASH overexpression hinders K63‐linked ubiquitination of Beclin 1. HeLa cells stably expressing vector or Flag-WASH were treated with CM or EBSS with or without BafA1 for 1 h and then stained with antibodies against endogenous Beclin 1 and K63‐linked polyubiquitin (K63‐Ub). The colocalization rate (Pearson's correlation coefficient) between Beclin 1 and K63‐Ub was calculated and shown in the right panel.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "(C) WASH overexpression inhibits LC3 lipidation. HeLa cells stably expressing vector or Flag-WASH were treated with CM or EBSS with or without BafA1 for 1 h and then stained with antibody against endogenous LC3. LC3 dots were calculated and shown in the right panel.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "(D) WASH deficiency increases K63‐linked ubiquitination of Beclin 1. WASH+/+ and WASH−/− MEFs were treated with EBSS at 37°C for 1 h and lysed for immunoprecipitation (IP) with anti‐Beclin 1 antibody and probed with antibody against K63‐linked poly‐ubiquitin.",
    "ncbi_link": "WASH: 68767"
  },
  {
    "caption": "(E) WASH overexpression inhibits Vps34 activity. HeLa cells were transfected with the indicated vectors and subjected to immunoprecipitation with anti‐Beclin 1 antibody for Vps34 kinase activity assay. Immunoprecipitates were separated into two equal parts, one for kinase assay and the other for input detection. RLU, relative light unit.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "(G) Ambra1 knockdown declines Beclin 1 ubiquitination. HeLa cells with Ambra1 knockdown were treated with EBSS for 1 h, followed by immunoprecipitated with anti‐Beclin 1 antibody. Immunoprecipitates were dissociated with 1% SDS and re‐immunoprecipitated with anti‐Beclin 1 antibody, followed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Ambra1: 55626"
  },
  {
    "caption": "(H) Ambra1 overexpression increases Beclin 1 ubiquitination. HeLa cells with Ambra1 overexpression were treated as above.",
    "ncbi_link": "Ambra1: 55626"
  },
  {
    "caption": "(J, K) WASH and Ambra1 competitively bind to Beclin 1. HeLa cells with vector or WASH overexpression were starved for 1 h and lysed for immunoprecipitation with anti‐Beclin 1 antibody (J). Recombinant Ambra1 and WASH proteins were incubated with GST-Beclin 1, followed by GST pull‐down assays (K). Scale bar, 10 μm. Data are shown as means±s.d. **P0.01 and ***P0.001. Data were repeated for at least three times with similar results.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "D. Mdm12 binds NBD-PE. Wild-type and monomeric (I5P mutant) Mdm12 were incubated with NBD-PE and separated from free NBD-PE in native PAGE. Coomassie staining (left) and fluorescent (right) detection indicates that Mdm12 directly interacts with NBD-PEin vitro.E. Quantitative data showing binding affinities for NBD-PE by Mdm12. The binding affinities of Mdm12 (monomer/dimer shown in Native PAGE and I5P mutant) for NBD-PE was measured with a NBD-PE concentration-dependent manner. All experiments were carried out three times and the means ± SD are given.",
    "ncbi_link": "Mdm12: 854153"
  },
  {
    "caption": "F. Mdm12 mutants (L256W, I262W, and L256W/I262W double mutant) were incubated with NBD-PE, and subjected to native PAGE. Because wild-type Mdm12 separates as both monomer and dimer on native PAGE, the purely monomeric form (I5P) of Mdm12 was used as the wild type for clarity. The graph in the right indicates the quantities measured in the experiments. The bar shows the relative amounts of the band ratio (fluorescence/Coomassie). Values represent the means and SD from three independent experiments.",
    "ncbi_link": "Mdm12: 854153"
  },
  {
    "caption": "A. Overall structure (left) and electron density (right) of Mdm12 in the asymmetric unit. Four molecules (two Mdm12 dimers) are organized with 2-fold rotation symmetry. The 2-fold axes are indicated with a black dotted line.B. Overall structure (left) and electron density (right) of ΔMdm12 in the asymmetric unit. Six ΔMdm12 molecules (three Mdm12 dimers) are arranged with 2-fold rotation symmetry as shown above.",
    "ncbi_link": "Mdm12: 854153"
  },
  {
    "caption": "(C) 293T cells were transfected with empty vector (EV), a vector encoding FLAG-tagged full length CYLD (wt), or constructs encoding FLAG-tagged CYLD fragments 1-581 (F1) lacking the C-terminus, or 581-956 (F2) lacking the N-terminus, as indicated, followed by FLAG-IP. The blot was probed with antibodies recognizing SPATA2, FLAG and tubulin. Endogenous SPATA2 was co-immunoprecipitated to comparable levels by CYLD and the C-terminal CYLD protein fragment, containing the USP domain.",
    "ncbi_link": "CYLD: 1540"
  },
  {
    "caption": "(D) CYLD-/- MEF were infected with retrovirus encoding FLAG-CYLD as indicated and CYLD was purified by FLAG-IP. The blot was probed with antibodies recognizing CYLD, SPATA2 and actin.",
    "ncbi_link": "CYLD: 1540"
  },
  {
    "caption": "(E) 293T cells were transfected with empty vector (EV), a vector encoding FLAG-tagged full length SPATA2 or a construct encoding the FLAG-tagged N-terminal part of SPATA2 (NT), as indicated, followed by FLAG-IP. The blot was probed with antibodies recognizing CYLD, SPATA2 and tubulin. M, marker lane.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "(A) 293T cells were transfected with a vector encoding V5-tagged full length SPATA2, along with empty vector (EV) a vector encoding FLAG-tagged HOIP wild-type (wt) or a vector encoding a FLAG-tagged PUB domain mutant of HOIP (N102A). After FLAG-IP, the blot was probed with antibodies recognizing HOIP, CYLD, V5 and actin.",
    "ncbi_link": "HOIP: 55072"
  },
  {
    "caption": "(B) 293T cells were transfected with empty vector or a vector encoding FLAG-tagged HOIP along with either V5-tagged SPATA2 (wt) or a V5-tagged PIM mutant (PIMmut) of SPATA2. After V5-IP, the blot was probed with antibodies recognizing FLAG, CYLD, V5 and tubulin.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "(D) 293T cells were transfected with empty vector, FLAG-SPATA2 or FLAG-HOIP. After FLAG-IP, the blot was probed with antibodies recognizing OTULIN, CYLD, FLAG and actin.",
    "ncbi_link": "HOIP: 55072
SPATA2: 9825"
  },
  {
    "caption": "(E) 293T cells were transfected with empty vector, V5-tagged SPATA2 (wt) or a V5-tagged PUB domain mutant PUBmut of SPATA2. After V5-IP, the blot was probed with antibodies recognizing CYLD, FLAG, V5 and tubulin.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "(A) A549 cells were infected to express a CRISPR/Cas9 system targeting luciferase (as control, indicated wt) or the spata2 gene (ko). Mixed cell cultures were treated with FLAG-huTNF (2µg/ml) for the indicated time. The purified TNF-RSC was sequentially probed with antibodies recognizing SPATA2, CYLD, HOIP, SHARPIN, TRADD, TNF and tubulin as indicated.",
    "ncbi_link": "luciferase: 
spata2: 9825"
  },
  {
    "caption": "(B) MEF were infected to express a CRISPR/Cas9 system targeting luciferase (wt) or the spata2 gene (ko). Single clones were generated, which were treated with FLAG-TNF (2µg/ml) for the indicated time. The purified TNF-RSC was sequentially probed with antibodies recognizing M1-linked ubiquitin, CYLD, RIPK1, and tubulin as indicated.",
    "ncbi_link": "luciferase: 
spata2: 263876"
  },
  {
    "caption": "FLAG-tagged CYLD or catalytically inactive FLAG-CYLD (C598A), respectively, were stably expressed in CYLD-/-MEF, followed by infection with control retrovirus, or retrovirus encoding SPATA2, and purified by FLAG-IP. Purified CYLD or the inactive mutant were added to recombinant di-ubiquitin for 0, 20 or 40 min at 37°C as indicated. After electrophoresis, the gel was cut and the lower part was silver stained to visualize mono-and di-ubiquitin, while the upper part was transferred to a membrane and probed for FLAG and V5. In (A), the experiment was done with M1-linked di-ubiquitin substrate, in (B) K63-linked di-ubiquitin substrate was subjected to the assay, and in (C) K48-linked di-ubiquitin substrate was analyzed.",
    "ncbi_link": "CYLD: 1540
SPATA2: 263876"
  },
  {
    "caption": "(A) MEF expressing CRISPR/Cas9 targeting luciferase (wt) or single clones generated from MEF expressing CRISPR/Cas9 targeting the spata2 gene (ko) were treated with mTNF (10 ng/ml) as indicated. The blots were probed with antibodies recognizing P-IkBαIkBα, P-p38, p38, P-JNK, JNK, P-p65, p65 and tubulin.",
    "ncbi_link": "luciferase: 
spata2: 263876"
  },
  {
    "caption": "(B) 15P-1 Sertoli cells expressing CRISPR/Cas9 targeting luciferase (as control) or single clones generated from 15P-1 Sertoli cells expressing CRISPR/Cas9 targeting the spata2 gene were treated with mTNF (10 ng/ml) as indicated. The blots were probed with antibodies recognizing P-IkBα, IkBα, P-p38, p38, P-JNK, JNK, P-p65, p65 and tubulin.",
    "ncbi_link": "luciferase: 
spata2: 263876"
  },
  {
    "caption": "(C) TAK1-/-MEF were infected to express a CRISPR/Cas9 system targeting luciferase or the spata2 gene, from which single clones were generated. The cells were treated with mTNF (10 ng/ml) or mTNF along with Necrostatin-1 (Nec-1) for 1-3 h as indicated. The blot was sequentially probed with antibodies recognizing PARP, cleaved caspase-3 and tubulin.",
    "ncbi_link": "luciferase: 
TAK1: 26409
spata2: 263876"
  },
  {
    "caption": "Top: Violin plots showing the expression level of CAMK2N1 and CAMK2N2 in three groups. Bottom: Scatter plot showing the correlations of foldchanges according to the expression of genes encoding CaMK family proteins between CTRL GINs and sMDD GINs and between sMDD with Trzd GINs and sMDD GINs. A linear regression line is added to the plot based on these two variables. sMDD+Trzd vs. sMDD, n=14 genes; CTRL vs. sMDD, n=14 genes.",
    "ncbi_link": "CAMK2N1: 55450
CAMK2N2: 94032"
  },
  {
    "caption": "(A) Immunofluorescence microscopy for POMC (green) and Cre (red; n=4), (B) POMC (green) and Atg7 (red; n=4) and (C) POMC (green) and p62 (red; n=6) in MBH sections from Con and Atg7F/F‐POMC‐Cre (KO) mice",
    "ncbi_link": "Cre: 
Atg7: 74244
POMC: 18976"
  },
  {
    "caption": "(D) TUNEL‐positivity (green; n=4) and (E) number of POMC‐positive neurons (red) in MBH sections from Con and KO mice (n=6). Values are mean±s.e.m. P values are as compared with diet‐ and age‐matched controls. *P0.05, ***P0.001. Nuclei are blue (DAPI). Scale inset: 10 μm. White arrows indicate Atg7, Cre, p62 or POMC signal. Yellow arrows indicate merged signal. Con, control; DAPI, 4′‐6‐diamidino‐2‐phenylindole; KO, knockout; MBH, mediobasal hypothalamic; NS, not statistically significant; POMC, proopiomelanocortin; TUNEL, TdT‐mediated dUTP nick end labelling.",
    "ncbi_link": "Cre: 
Atg7: 74244
POMC: 18976"
  },
  {
    "caption": "(I) Immunofluorescence microscopy for POMC (green) and α‐MSH (red), and (J) α‐MSH (green) in MBH from Con and KO mice on RD (n=5). Values are mean±s.e.m. P values are as compared with diet‐ and age‐matched controls. *P0.05, **P0.01, ***P0.001. Nuclei are blue (DAPI). Scale inset: 10 μm. Yellow arrows indicate merged signal. ACTH, adrenocorticotrophic hormone; Con, control; DAPI, 4′‐6‐diamidino‐2‐phenylindole; eWAT, epididymal fat; HDF, high‐fat diet; KO, knockout; MBH, mediobasal hypothalamic; mo, month; MSH, melanocyte‐stimulating hormone; NPY, neuropeptide Y; POMC, proopiomelanocortin; RD, regular chow; wt, weight.",
    "ncbi_link": "POMC: 18976
proopiomelanocortin: 18976"
  },
  {
    "caption": "(H) Immunoblot for oxidized proteins in eWAT from RD‐fed Con and KO mice (n=3). (I) FACS analysis for M1 and M2 macrophage proportions in adipose stromal vascular fractions from fed Con and KO mice on RD (n=3). Values are mean±s.e.m. P values are as compared with diet‐ and age‐matched controls. *P0.05, **P0.01, ***P0.001. Con, control; eWAT, epididymal fat; FACS, fluorescence‐activated cell sorting; HDF, high‐fat diet; Iso, isoproterenol; KO, knockout; POMC, proopiomelanocortin; RD, regular chow; Stv, fasted.",
    "ncbi_link": "POMC: 18976
proopiomelanocortin: 18976"
  },
  {
    "caption": "(L) Insulin tolerance tests and (M) body weights of 1‐mo‐old Con and KO mice on RD (n=3-5). Values are mean±s.e.m. P values are as compared with diet‐ and age‐matched controls. *P0.05, **P0.01, ***P0.001. Con, control; HDF, high‐fat diet; HOMA, homeostasis model of insulin resistance; KO, knockout; mo, month; POMC, proopiomelanocortin; RD, regular chow; Stv, fasted.",
    "ncbi_link": "POMC: 18976
proopiomelanocortin: 18976"
  },
  {
    "caption": "(B) Volcano plot showing differentially expressed genes between WT (WT1 and WT2) and patient  (V.1 (F1), V.5 (F1)) primary dermal fibroblasts. The vertical axis (y-axis) shows the -log10 P-value, whereas the horizontal axis (x-axis) displays the log2 fold change value. The red dots represent the upregulated transcripts; the blue dots represent the downregulated transcripts. A total of 172 genes were found significantly dysregulated. TAPT1, a gene located in the IBD region, appeared among the most significantly downregulated genes in the patients.",
    "ncbi_link": "TAPT1: 202018"
  },
  {
    "caption": "(B) qPCR results using specific primers for TAPT1  and TAPT1-AS1  in 3 WT (WT1, WT2 , V.2 (F1)) and 3 affected (V.1 (F1), V.5 (F1), IV.1 (F2)) primary fibroblasts. TAPT1  mRNA is significantly reduced in all patients  compared to WTs, whereas TAPT1-AS1  transcript levels are unaffected. Fold change relative to V.2 (F1) is plotted as mean ± SD. Asterisks indicate conventional statistical significance (Student t-test; n.s. p-value > 0.05, **** p-value < 0.0001).",
    "ncbi_link": "TAPT1: 202018
TAPT1-AS1: 202020"
  },
  {
    "caption": "(D) qPCR  analysis of TAPT1  expression in 3 WT (WT1, WT2, WT3) and 3 affected (V.1 (F1), V.5 (F1), IV.1 (F2)) primary fibroblasts  treated with cycloheximide  (CHX). CHX  was used to block nonsense mediated decay (NMD). Our results showed a time dependent increase in the level of TAPT1  transcripts in all 3 patient cells while TAPT1  RNA level remained constant in the WT cells. For each graph, fold change relative to non-treated condition is plotted as mean ± SD. Asterisks indicate conventional statistical significance (Student t-test; n.s. p-value > 0.05, **** p-value < 0.0001).",
    "ncbi_link": "TAPT1: 202018"
  },
  {
    "caption": "(B) qPCR  validation test for 3 top dysregulated genes (RARRES2, ZIC1, and ZIC4) detected by  RNA-seq. The analysis was performed on RNA samples independent from those sent for RNA-seq for 2 WTs (WT1 and WT2) and 2 patients  (V.5 (F1) and IV.1 (F2)). Fold change relative to WT1 is plotted as mean ± SD of three technical replicates. Asterisks indicate statistical significance (Student t-test; *** p-value < 0.001, **** p-value < 0.0001).",
    "ncbi_link": "RARRES2: 5919
ZIC1: 7545
ZIC4: 84107"
  },
  {
    "caption": "(b) We transfected MEFs stably expressing mCherry-EGFP-LC3 with BFP-tagged AR25Q or AR125Q. Cells were imaged after 24 h, and yellow puncta (autophagosomes) and red puncta (autolysosomes) in AR-expressing (blue) cells were counted. Autophagosomes: n = 3 independent experiments, F = 20.65; autolysosomes: n = 3 independent experiments, F = 4.49. One-way ANOVA with post hoc Tukey test. *P 0.05, **P 0.01, ***P 0.001. n = 33 cells per genotype.",
    "ncbi_link": "AR: 367
AR125Q: 367
AR25Q: 367"
  },
  {
    "caption": "(a,b) Electron micrographs of motor neuron perinuclear regions from age-matched non-transgenic (Nt), YAC AR20 and YAC AR100 transgenic mice before disease onset (a, 6 months of age) and after prominent neuromuscular and molecular pathology is apparent (b, 14 months of age). (a) At 6 months of age, occasional autophagosomes (yellow arrowheads) are noted in Nt, YAC AR20 and YAC AR100 at roughly equivalent frequency. Autolysosomes (red arrowheads) are much more common and are present in higher numbers in YAC AR20 and YAC AR100 motor neurons. (b) At 14 months of age, when YAC AR100 mice display signs of motor neuronopathy and molecular pathology, we observed many YAC AR100 motor neuron micrographs with frequent autophagosomes (yellow arrowheads). Despite this increase in autophagosomes, autolysosomes were fewer in number at this age in YAC AR100 motor neurons, such that autophagosome numbers approached autolysosome numbers in YAC AR100 motor neurons. This was never the case for Nt motor neurons or YAC AR20 motor neurons. Main panels are at original magnification 2,200× and insets are at original magnification 3,700×.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(a) Mean number of autophagosomes per motor neuron field in electron micrographs from non-transgenic (Nt), YAC AR20 and YAC AR100 transgenic mice at 6 and 14 months of age, ± s.e.m. 6 months: n = 3 independent experiments, F = 0.63, one-way ANOVA with post hoc Tukey test. P = 0.534. 14 months: n = 3 independent experiments, F = 4.32, one-way ANOVA with post hoc Tukey test. *P 0.05. (b) Mean number of autolysosomes per motor neuron field in electron micrographs from Nt, YAC AR20 and YAC AR100 transgenic mice at 6 and 14 months of age, ± s.e.m. 6 months: n = 3 independent experiments, F = 4.18, one-way ANOVA with post hoc Tukey test. *P 0.05. 14 months: n = 3 independent experiments, F = 4.56, one-way ANOVA with post hoc Tukey test. *P 0.05. (c) Mean autophagy index, dividing number of autolysosome by number of autophagosomes for each motor neuron field, ± s.e.m. At 6 months, YAC AR100 motor neurons displayed a markedly increased autophagy index; n = 3 independent experiments, F = 129.81, one-way ANOVA with post hoc Tukey test. **P 0.01. However, once YAC AR100 mice develop disease pathology at 14 months, the autophagy index for YAC AR100 motor neurons is significantly decreased; n = 3 independent experiments, F = 82.82, one-way ANOVA with post hoc Tukey test. **P 0.01. Individual P values and degrees of freedom are available in the Supplementary Methods Checklist.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(a) HEK293 cells were transfected with TFEB and AR25Q or AR125Q, as indicated. Immunoprecipitation (IP) was performed with anti-TFEB antibody, followed by immunoblotting (IB) for TFEB and AR. Untransfected HEK293 cells served as a negative control, and no AR was observed with IgG antibody only (not shown).",
    "ncbi_link": "AR: 367
AR125Q: 367
AR25Q: 367
TFEB: 7942"
  },
  {
    "caption": "(b) We transfected MN-1 cells with the 4X-CLEAR luciferase reporter and treated cells with sucrose to induce TFEB activation. Untreated: n = 3 independent experiments, F = 3.48, one-way ANOVA with post hoc Tukey test. **P 0.01. Sucrose treatment: n = 3 independent experiments, **P 0.01, t-test, WT t(10) = 8.133; ***P 0.001, t-test, AR 24Q t(10) = 6.11; P not significant (n.s.), AR 65Q t(10) = 0.644. Sucrose-treated MN-1 AR24Q cells displayed significantly higher 4X-CLEAR luciferase activity: n = 3 independent experiments, F = 2.49, one-way ANOVA with post hoc Tukey test. ***P 0.001. All ratios were normalized to untreated MN-1 WT cells, whose value was set to 1.",
    "ncbi_link": "luciferase: 
AR: 367"
  },
  {
    "caption": "(c) We exposed MN-1 cells to ammonium chloride, an inhibitor of lysosomal activity, to determine the capacity for TFEB induction. RT-PCR analysis revealed lack of TFEB target gene induction in MN-1 AR65Q cells for four gene targets: Lamp1 (lysosomal-associated membrane protein 1), F = 37.51; Atp6v1h (vesicular ATPase V1 subunit H), F = 57.26; Mcoln1 (mucolipin 1), F = 251.0; and Gla (galactosidase-α), F = 75.51; n = 3 independent experiments, *P 0.05, **P 0.01, ANOVA with post hoc Tukey test. For Lamp1 and Mcoln1, MN-1 AR24Q cells yielded significantly higher expression. Differences in the expression of TFEB target genes at baseline were negligible.",
    "ncbi_link": "AR: 367
Atp6v1h: 108664
Gla: 11605
Lamp1: 16783
Mcoln1: 94178
TFEB: 21425"
  },
  {
    "caption": "(d) We measured expression levels of TFEB target genes in E13 motor neurons derived from non-transgenic (Nt), YAC AR20 and YAC AR100 mice by RT-PCR analysis: Ctsf (cathepsin F), F = 4.63; Mcoln1, F = 6.64; Atp6v1h, F = 5.6; and Gla, F = 5.65; n = 3 independent experiments, *P 0.05, ANOVA with post hoc Tukey test. Data are presented as mean ± s.e.m. Individual P values and degrees of freedom are available in the Supplementary Methods Checklist.",
    "ncbi_link": "AR: 367
Atp6v1h: 108664
Ctsf: 56464
Gla: 11605
Mcoln1: 94178
TFEB: 21425"
  },
  {
    "caption": "(a) We transfected MN-1 cells with the 4X-CLEAR luciferase reporter and with BFP-tagged TFEB or BFP empty vector, and then measured luciferase activity. Marked induction of luciferase activity occurred with BFP-TFEB; n = 3 independent experiments, ***P 0.001, t-test, WT t(4) = 48.79; ***P 0.001, t-test, AR 24Q t(4) = 22.91; ***P 0.001, t-test, AR 65Q t(4) = 14.02. Results for each line were normalized to the BFP-empty luciferase activity.",
    "ncbi_link": "AR: 367
TFEB: 21425"
  },
  {
    "caption": "(b) We transfected MN-1 AR65Q cells with the 4X-CLEAR luciferase reporter and with BFP-TFEB or BFP empty vector and subjected the MN-1 AR65Q cells to conditions that promote TFEB activation, as shown. MN-1 WT cells were also transfected with the 4X-CLEAR luciferase reporter and BFP empty vector and subjected to the identical treatments for control purposes. Results are shown normalized to untreated MN-1 WT cells expressing BFP-empty. Untreated, F = 182.7; starvation, F = 63.64; NH4Cl, F = 291.9; Rapamycin, F = 3128; ANOVA with post hoc Tukey test. **P 0.01, ***P 0.001.",
    "ncbi_link": "luciferase: 
AR: 367
TFEB: 21425"
  },
  {
    "caption": "(c) We transfected MN-1 AR65Q cells with the mCherry-EGFP-LC3 construct and with either BFP-empty or BFP-TFEB. Autophagic vesicles forming in BFP-expressing cells were then detected as red, green or yellow puncta, as shown. Scale bar, 20 μm. (d) Left, quantification of autophagic vesicle type. Note marked reduction in autophagosomes in MN-1 AR65Q cells expressing BFP-TFEB; n = 3 independent experiments, F = 16.596, ANOVA with post hoc Tukey test. **P 0.01, ***P 0.001. Right, calculation of the autophagy index; n = 3 independent experiments, F = 24.43, ANOVA with post hoc Tukey test. **P 0.01. Data are presented as mean ± s.e.m. Individual P values and degrees of freedom are available in the Supplementary Methods Checklist.",
    "ncbi_link": "AR: 367
TFEB: 21425"
  },
  {
    "caption": "(b) HEK293 cells were transfected with TFEB and influenza hemagglutinin (HA)-tagged full-length AR25 (FL) or a C-terminal AR mutant (m1, m2, m3, m4). Immunoprecipitation (IP) was performed with anti-TFEB antibody, followed by immunoblotting (IB) for TFEB and AR. Untransfected HEK293 cells served as a negative control, and no AR was observed with IgG antibody only (not shown).",
    "ncbi_link": "AR: 367
TFEB: 7942"
  },
  {
    "caption": "(c) HEK293 cells were transfected with TFEB and HA-tagged N-terminal AR mutant containing a 19Q or 112Q tract (NT19Q, NT112Q). Immunoprecipitation was performed as in b. with anti-TFEB antibody, followed by immunoblotting (IB) for TFEB and AR. Untransfected HEK293 cells served as a negative control, and no AR was observed with IgG antibody only (not shown).",
    "ncbi_link": "AR: 367
TFEB: 7942"
  },
  {
    "caption": "(f) We transfected MN-1 WT cells with the 4X-CLEAR luciferase reporter and either BFP-empty or AR25Q-BFP, under standard culture conditions (control), ammonium chloride treatment or rapamycin treatment. Control, t(3) = 15.73; NH4Cl, t(4) = 4.108; rapamycin. t(4) = 4.58; t-test. **P 0.01.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(g) We transfected MN-1 AR24Q cells with either scrambled shRNA control vector or AR shRNA vector and measured 4X-CLEAR luciferase reporter activity under baseline conditions (control) or after rapamycin. Control, t(4) = 0.51; rapamycin, t(4) = 7.15; t-test. **P 0.01.",
    "ncbi_link": "AR: 11835
AR: 367///11835"
  },
  {
    "caption": "(h) RT-PCR analysis of MN-1 AR24Q cells transfected with scrambled shRNA control or AR shRNA vector: Gla, t(4) = 4.77; Atp6v1h, t(4) = 3.75; Mcoln1, t(4) = 13.74; Ctsd (cathepsin D), t(4) = 7.91; and Lamp1, t(4) = 6.46; n = 3 independent experiments, *P 0.05, **P 0.01, t-test. Data are presented as mean ± s.e.m. Individual P values and degrees of freedom are available in the Supplementary Methods Checklist.",
    "ncbi_link": "AR: 367
AR: 11835
Atp6v1h: 108664
Ctsd: 13033
Gla: 11605
Lamp1: 16783
Mcoln1: 94178"
  },
  {
    "caption": "(e) We isolated RNAs from SBMA and control NPC lines (three different NPC lines per human subject) and then measured the expression levels of TFEB target genes including CYCS (cytochrome c), t(4) = 2.844; MCOLN1, t(4) = 3.246; GLA, t(4) = 3.174; ACADM (acyl-CoA dehydrogenase), t(4) = 4.405; COX6A1 (cytochrome oxidase 6A1), t(4) = 5.584; and the TFEB gene itself, t(4) = 0.593. Significant expression reductions were noted in SBMA NPC lines for all tested TFEB target genes. *P 0.05, **P 0.01. Data in d,e are presented as mean ± s.e.m. Individual P values and degrees of freedom are available in the Supplementary Methods Checklist.",
    "ncbi_link": "ACADM: 34
COX6A1: 1337
CYCS: 54205
GLA: 2717
MCOLN1: 57192
TFEB: 7942"
  },
  {
    "caption": "(a) Control and SBMA NPC lines were maintained in the presence or absence of the AR ligand dihydrotestosterone (DHT) and then harvested for immunoblotting analysis after TFEB antibody immunoprecipitation (IP). Immunoblotting (IB) for AR confirmed expression of AR in control (Ctrl) and SBMA NPCs, and immunoblotting for TFEB confirmed the interaction of AR with TFEB in both control and SBMA NPCs.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(b) We transfected SBMA NPC lines (three different NPC lines per patient) with either the BFP-empty vector or BFP-TFEB expression construct, treated the NPCs with JC-1 dye and counted the percentage of cells with depolarized mitochondria. Results are presented as Tukey box plots with boxes corresponding to first and third quartiles from the median and whiskers corresponding to 1.5 quartiles from the median; n = 3 independent experiments, *P 0.05, t-test, t(6) = 3.217.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(c) Representative images from transfection of SBMANPCs with the mCherry-EGFP-LC3 vector and either BFP-empty vector or BFP-TFEB expression construct. BFP-empty vector-expressing SBMANPCs display a preponderance of yellow puncta (autophagosomes), while BFP-TFEB-expressing SBMANPCs exhibit a shift toward almost entirely red puncta (autolysosomes), consistent with rescue of the autophagic flux defect. Scale bars, 20 μm. (d) We transfected SBMANPC lines (three different NPC lines per patient) with the mCherry-EGFP-LC3 vector and either BFP-empty vector or BFP-TFEB expression construct, counted the number of autophagosomes and autolysosomes in BFP-expressing NPCs and determined the number of autophagic vesicles per cell. TFEB overexpression markedly reduced autophagosome formation in SBMANPCs. ***P 0.001; t-test, t(30) = 4.373. Data in d are presented as mean ± s.e.m. Individual P values are available in the Supplementary Methods Checklist.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Flow cytometric analysis of γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse and line the median. *p < 0.05, **p < 0.01, ***p < 0.001 using Mann-Whitney test. Numbers of γδT17 cells in the LN (A) and skin (B) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 8; 4 experiments, IMQ: n = 11-12; 4 experiments.",
    "ncbi_link": "CRE: 2777477
Cre: 2777477
RORγ: 19885
STAT3: 20848"
  },
  {
    "caption": "Flow cytometric analysis of γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). In graphs, each symbol represents a mouse and line the median. Numbers of γδT17 cells in the LN and skin (staining as in Fig EV1) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 6; 3 experiments, IMQ: n = 11; 4 experiments.",
    "ncbi_link": "STAT4: 20849"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-17A (A) or IL-17F (D) and IFNγ production in γδ T cells before (steady-state) and after IMQ-induced psoriasis. Numbers in gate indicate % positive cells; numbers outside the gate indicate mean fluorescence intensity of IL-17A or IL-17F. (B, E) Frequency of IL-17A+ (B) and IL-17F+ (E) γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (C, F) Quantification of mean fluorescence intensity (MFI) of IL-17A (C) and IL-17F (F) staining in γδ T cells after IMQ-induced psoriasis (each color represents a different experiment).",
    "ncbi_link": "CRE: 2777477
Cre: 2777477
RORγ: 19885
STAT3: 20848"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-22 and IL-17A production in γδ T cells (A) and frequency of IL-22+ γδ T cells (B) before (steady-state) and after (IMQ) IMQ-induced psoriasis. Steady-state: n = 6; 3 experiments, IMQ: n = 8-9; 3 experiments.",
    "ncbi_link": "CRE: 2777477
Cre: 2777477
RORγ: 19885
STAT3: 20848"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in RORγtCRE-STAT3F/F (Cre+) and littermate control mice (Cre−). In graphs, each symbol represents a mouse or experiment and line the median. Representative dot plots showing IL-22 and IL-17A production in γδ T cells (C) and frequency of IL-22+ γδ T cells (D) following culture without (−) or with 40ng/ml recombinant IL-23 (n = 9-10, 3 experiments).",
    "ncbi_link": "CRE: 2777477
Cre: 2777477
RORγ: 19885
STAT3: 20848"
  },
  {
    "caption": "Frequency of IL-22+ γδ T cells following culture with IL-1β, IL-23 or nothing. Each symbol represents one experiment. Open circles = Cre+ (each color represents a different culture condition).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). (A, ) Frequency of IL-17A+ (A) γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (B) Frequency of IL-17F+ γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis. (C) Quantification of mean fluorescence intensity (MFI) of IL-17A staining in γδ T cells after IMQ-induced psoriasis (D) Quantification of mean fluorescence intensity (MFI) of IL-17F staining in γδ T cells after IMQ-induced psoriasis.",
    "ncbi_link": "STAT4: 20849"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). Frequency of IL-22+ γδ T cells before (steady-state) and after (IMQ) IMQ-induced psoriasis.",
    "ncbi_link": "STAT4: 20849"
  },
  {
    "caption": "Flow cytometric analysis of lymph node γδ T cells in STAT4−/− (−/−) and littermate control mice (+/−). Frequency of IL-22+ γδ T cells following culture without (−) or with 40ng/ml recombinant IL-23",
    "ncbi_link": "STAT4: 20849"
  },
  {
    "caption": "(C) Representative western blots showing ADCK3, SQR, TST, ETHE1 and SUOX in two control (EV) and six ADCK3-depleted clones (ADCK3 RNAi). (D) Quantification of proteins levels in ADCK3-depleted clones (ADCK3 RNAi) relative to controls (EV).",
    "ncbi_link": "ADCK3: 56997"
  },
  {
    "caption": "(L) Immunoblotting of DR5 confirming generation of knock out (DR5-KO) cell lines.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(M) Cell viability analysis of DR5-KO and DR5-WT cells (n=3).",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(N) DR5-KO and WT cells were treated with TNFα and indicated DR5 agonist followed by flow cytometry using PD-L1 specific antibodies.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(O) TNBC WT and DR5-KO (MDA-MB-436) cells were treated with either DR5 agonist or TNFα as indicated. Lysates were analyzed for PD-L1, S5a and DR5. GAPDH is loading control.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(P) OVCAR-3 and MDA-MB-436 (WT and DR5-KO) cells were treated with KMTR2 followed by ubiquitin and S5a immunoblotting from total lysates. GAPDH is loading control.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(F) ApoEVs isolated from DR5 sensitive tumor cells grown in Met-HPG+ media were added on to DR5-KO cells (growing in regular media). After 48 hrs flow cytometry analysis was carried out with HPG catalyzing dye. HPG incorporation from flow cytometry data confirms ApoEVs transfer from cells growing in Met-HPG+ (DR5-WT) to DR5-KO cells.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(G) ApoEVs isolated from DR5-WT OVCAR-3 cells (KMTR2 treated) were added on to DR5-KO (MDA-MB-231) cells for indicated times (24-96 hrs) to analyze PD-L1 transfer kinetics from ApoEVs",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "after addition of MDA-MB-436 derived ApoEVs (treated with combination of KMTR2+lexatumumab DR5 agonists or IgG1) on to DR5-KO MDA-MB-231 cells, total lysates were immunoblotted for PD-L1 after 24 hrs. KMTR2+lexatumumab (n=3), IgG1 (n=2).",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "(I) Left: PD-L1 surface histogram shows direct antibody treatment on DR5-KO cells. Right: PD-L1 surface histogram from DR5-KO cells after treatment (24 hrs) with ApoEVs isolated from DR5 sensitive cells after either Lexa or KMTR2 treatment.",
    "ncbi_link": "DR5: 8795"
  },
  {
    "caption": "a. Cells were transfected with the TMEM55B-myc-DDK plasmid for 24 h and then treated with 40 μM acrolein for 2 h. Cell lysates were immunoprecipitated with flag magnetic beads and immunoblotted with the indicated antibodies.",
    "ncbi_link": "myc: 
TMEM55B: 90809"
  },
  {
    "caption": "SH-SY5Y cells transfected with indicated siRNAs for 48 h were treated with 40 μM acrolein for 2 h. Cell lysates were subjected to Phos-tag PAGE and immunoblotted with anti-JIP4 antibody (f, left). CaMK2G knockdown efficiency was confirmed by qRT-PCR.; ***p <0.001, n=3 technical replicates. Values are mean ± SD. At least three experiments were replicated (f, right).",
    "ncbi_link": "CaMK2G: 818"
  },
  {
    "caption": "c. GFP or GFP-ALG2 transfected TRPML1-mCherry stably expressing cells were treated with acrolein for 2 h. Cell lysates were immunoprecipitated with anti-RFP magnetic beads and immunoblotted with the indicated antibodies.",
    "ncbi_link": "GFP: 
mCherry: 
ALG2: 85365
TRPML1: 57192"
  },
  {
    "caption": "f. SH-SY5Y cells transfected with GFP or GFP-ALG2 for 24 h were treated with acrolein for 2 h and then spatial proximity of JIP4 and GFP was detected by a PLA using JIP4 and GFP antibodies.",
    "ncbi_link": "GFP: 
ALG2: 85365"
  },
  {
    "caption": "Parental and JIP4 KO SH-SY5Y cells were treated with 40 µM acrolein with or without 100 nM bafilomycin A1 for 2 h (a). Cell lysates were immunoblotted with the indicated antibodies. Autophagic flux was determined as the LC3-II production rate calculated as the level of LC3-II with bafilomycin A1 treatment.",
    "ncbi_link": "JIP4: 9043"
  },
  {
    "caption": "f. (left) SH-SY5Y cells were transfected with TMEM55B siRNAs for 48 h and then treated with 40 µM acrolein and 500 µM H2O2 or cultured in starvation medium for 2 h. Cells were fixed and stained with anti-γ-tubulin (green) and anti-LAMP2 (red) antibodies. Nuclei were stained with DAPI (blue). Scale bar, 20 μm. (right) Clustered relative to whole lysosomes were quantified as lysosomal clustering value. ***",
    "ncbi_link": "TMEM55B: 90809"
  },
  {
    "caption": "b. Parental and JIP4 KO SH-SY5Y cells were treated with various concentrations of acrolein for 24 h. Cytotoxicity was measured by an LDH assay. c. SH-SY5Y cells were transfected with TRPML1 siRNAs for 48 h and then treated with various concentrations of acrolein for 24 h. Cytotoxicity was measured by an LDH assay.",
    "ncbi_link": "TRPML1: 57192
JIP4: 9043"
  },
  {
    "caption": "A. Analysis of cytokine expression by CD4T cells isolated from the spleen. Data are representative FACS plots, gated on VD-TCRβ+CD4+CD44+cells (upper row) with mean frequencies among CD4T cells per group ± SEM, and (lower row) with mean frequencies per group.Cells (A-D) were isolated at day 9 after immunization and restimulated in the presence of MOG for 6 h. Data consist of n=5 WT PBS, n=4 WT PTx, n=4 IL-1R1-/- PBS, n=4 IL-1R1-/- PTx, MOG/CFA immunized mice. *p < 0.05, **p < 0.01, ***p < 0.001, N.S. - not significant; two-tailed unpaired t-test. Experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "B. Frequencies and total numbers (mean +SEM) of MOG-specific Th17 cells isolated from the dLN.Cells (A-D) were isolated at day 9 after immunization and restimulated in the presence of MOG for 6 h. Data consist of n=5 WT PBS, n=4 WT PTx, n=4 IL-1R1-/- PBS, n=4 IL-1R1-/- PTx, MOG/CFA immunized mice. *p < 0.05, **p < 0.01, ***p < 0.001, N.S. - not significant; two-tailed unpaired t-test. Experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "C-D. Frequencies and total numbers (mean +SEM) of MOG-specific GM-CSF+ Th17 cells isolated from the spleen (C) and dLN (D).Cells (A-D) were isolated at day 9 after immunization and restimulated in the presence of MOG for 6 h. Data consist of n=5 WT PBS, n=4 WT PTx, n=4 IL-1R1-/- PBS, n=4 IL-1R1-/- PTx, MOG/CFA immunized mice. *p < 0.05, **p < 0.01, ***p < 0.001, N.S. - not significant; two-tailed unpaired t-test. Experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "A-C. (A) Mean, (B) maximal EAE clinical scores and (C) area under the curve (AUC) of mice immunized with MOG/CFA/PTx. Data shown as (A) mean (+SEM), (B, C) individual plots with mean and are combined from at least four independent experiments and consist of n=41 WT, n=24 IL-1R1ΔT, n=18 IL-1R1-/-mice. *p < 0.05, ***p < 0.001; two-tailed unpaired t-test. Black (*) signs in (A) represent statistical analysis of IL-1R1ΔT vs WT and blue (*) of IL-1R1ΔT vs IL-1R1-/- groups.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "L-N. Analysis of CCR6 expression by CD4 T cells isolated from the dLN and CNS of EAE diseased mice. Data (L) are representative FACS histogram overlays of (black) control, (blue) IL-1R1ΔTcells, gated on CD3+CD4+IL-17A+cells; and of (black filled) control, (blue filled) IL-1R1ΔTcells, gated on CD3+CD4+IL-17A-cells. (M) Mean fluorescent intensity (mean +SEM) of CCR6 staining by CD4 T cells, shown in (L). (N) Mean fluorescent intensity (mean +SEM) of CCR6 staining by GM-CSF+ and GM-CSF-Th17 cells isolated from CNS, shown in (L).",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "D-G. Analysis of cytokine expression by cells isolated from WT (black), IL-1R1ΔT (blue) and IL-1R1-/- (red) mice and cultured with or without IL-23. Data (D) are representative FACS plots, gated on VD-TCRβ+cells with mean frequencies per group.Cells (A-G) were isolated from dLN and the spleen of MOG/CFA immunized mice, cultured under indicated conditions for four days and restimulated with MOG for 6 h prior to analysis. Data consist of n=4 of each genotype.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "D-G. Analysis of cytokine expression by cells isolated from WT (black), IL-1R1ΔT (blue) and IL-1R1-/- (red) mice and cultured with or without IL-23. Data (D) are representative FACS plots, gated on VD-TCRβ+cells with mean frequencies per group. Quantification (mean +SEM) of (E) MOG-specific Th17 cells, (F) GM-CSF+Th17 cells and (G) GM-CSF+IFNγ+Th17 cells.Cells (A-G) were isolated from dLN and the spleen of MOG/CFA immunized mice, cultured under indicated conditions for four days and restimulated with MOG for 6 h prior to analysis. Data consist of n=4 of each genotype.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "H-I. (H) Mean EAE clinical scores (+SEM) of Rag1-/- mice which received 1 x 105 IL-17A+cells of indicated genotypes and (I) total cell numbers (mean +SEM) of infiltrates isolated from CNS and used for further analysis.Data (H-L) consist of Rag1-/-mice which received WT (n=6), IL-1R1ΔT (n=3) and IL-1R1-/- (n=4) cells polarized in the presence of IL-23 prior to transfer. All experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177
Rag1: 19373"
  },
  {
    "caption": "H-I. Rag1-/- mice which received 1 x 105 IL-17A+cells of indicated genotypes and (I) total cell numbers (mean +SEM) of infiltrates isolated from CNS and used for further analysis.Data (H-L) consist of Rag1-/-mice which received WT (n=6), IL-1R1ΔT (n=3) and IL-1R1-/- (n=4) cells polarized in the presence of IL-23 prior to transfer. All experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177
Rag1: 19373"
  },
  {
    "caption": "J-L. Analysis of cytokine expression by CD4 T cells isolated from CNS of mice shown in (H) and restimulated with MOG for 6 h. (C) Data are representative FACS plots, gated on VD-TCRβ+cells (upper row) with mean frequencies ± SEM.Data (H-L) consist of Rag1-/-mice which received WT (n=6), IL-1R1ΔT (n=3) and IL-1R1-/- (n=4) cells polarized in the presence of IL-23 prior to transfer. All experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177
Rag1: 19373"
  },
  {
    "caption": "J-L. Analysis of cytokine expression by CD4T cells isolated from CNS of mice shown in (H) and restimulated with MOG for 6 h. (C) Data are representative FACS plots, gated on VD-TCRβ+cells (upper row) with mean frequencies ± SEM.Data (H-L) consist of Rag1-/-mice which received WT (n=6), IL-1R1ΔT (n=3) and IL-1R1-/- (n=4) cells polarized in the presence of IL-23 prior to transfer. All experiments were performed at least twice with similar results.",
    "ncbi_link": "IL-1R1: 16177
Rag1: 19373"
  },
  {
    "caption": "A. Mean EAE clinical scores (+SEM).Data consist of (A) n=10 WT, n=4 IL-1R1-/- PBS, n = 4 WT, n=4 IL-1R1ΔT and n=5 IL-1R1-/- PC61 treated mice.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "D. Analysis of IL-1R1 expression by Th17 cells isolated from CNS of EAE diseased mice, shown in (B). Data are representative FACS histogram overlays of cells isolated from (grey) wild type mice treated with PBS, (black) wild type, (blue) IL-1R1ΔT and (red) IL-1R1-/-mice treated with PC61, gated on VD-TCRβ+CD4+IL-17A+cells.",
    "ncbi_link": "IL-1R1: 16177"
  },
  {
    "caption": "A Pulldown and Western blot analysis validated the interaction between the viral protein ORF3a and its interactors, VPS11 and CLCC1, and the binding of S protein to SPCS2. HEK293T cells with SFB-tagged bait expression were collected and lysed. Cell lysates were subjected to pulldown assay using S-protein beads. Western blot analysis was conducted with the indicated antibodies. Cells transfected with vector or construct encoding control genes were included as controls in these experiments.",
    "ncbi_link": "SFB: "
  },
  {
    "caption": "B Immunostaining analysis of protein localization. U2OS cells were transfected with construct encoding ORF3a. Cells were fixed and stained with the indicated antibodies. The green signal is CLCC1 or lysosome marker LAMP1, the red signal is flag (for SFB-ORF3a), and the blue signal indicates DAPI/nuclei. Scale bar: 10 µm.",
    "ncbi_link": "ORF3a: 43740569"
  },
  {
    "caption": "B Comparison of SARS-CoV-2 virus-host interaction to the genetic screening with CRISPR technique. Two different MOIs (MOI 0.01 and MOI 0.3) were used in these screens and we compared our results with both of these datasets. Blue dots are the identified genes from the genetic screening. Orange dots are the highlighted overlapped genes between our virus-host interaction study and the results from the genetic screening. Top five overlapped genes are indicated.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "B Pulldown and Western blot validation of the interaction between N protein and G3BP1/G3BP2. Cells transfected with vector or construct encoding GFP or N protein from different human coronaviruses were compared in these experiments.",
    "ncbi_link": "N protein: 43740575"
  },
  {
    "caption": "C,D Effect of SARS-CoV-2 N protein on stress granule formation. A549 (C) and MCF10A (D) cells were transfected with pinducer20-N protein of SARS-CoV-2. All the cells are treated with sodium arsenite but with or without Dox to induce N protein expression. Cells were fixed and stained with the indicated antibodies. The green signal is G3BP1, the red signal is HA (for N protein), and the blue signal indicates DAPI/nuclei. Scale bar: 10 µm.",
    "ncbi_link": "N protein: 43740575"
  },
  {
    "caption": " (B) Cytoplasmic TDP-43 immunostaining is elevated not only in poly-GA transduced neurons, but also in the non-transduced receiver cells. White and red arrows indicate cells with cytoplasmic TDP-43 in GFP positive and negative cells, respectively. ",
    "ncbi_link": "GFP: 
poly-GA: 203228"
  },
  {
    "caption": " (C) Automated quantification of cells with cytoplasmic TDP-43 in GFP or GA175-GFP transduced (donor), non-transduced (receiver) neurons. Cells with and without GFP signal were counted separately (indicated by +/­­−). Two groups (GFP negative donor, GFP positive receiver) were excluded due to very high GFP transduction rate and very low GFP transmission rate. n=4 biological replicates. In total 283 donor GFP, 273 donor GA175-GFP, 284 receiver GFP and 266 receiver GA175-GFP cells were analyzed. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. *** denotes p<0.001. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " Co-culture model in HeLa cells transfected with iRFP or GA175-iRFP in the donor compartment and TDP-43ΔNLS-GFP in donor and receiver compartment. Immunofluorescence staining of TDP-43∆NLS aggregate number per cell ",
    "ncbi_link": "GFP: 
iRFP: 
GA: 203228
TDP-43: 23435"
  },
  {
    "caption": " Co-culture model in HeLa cells transfected with iRFP or GA175-iRFP in the donor compartment and TDP-43ΔNLS-GFP in donor and receiver compartment. automatic quantification of TDP-43∆NLS aggregate number per cell In (E) n=3 biological replicates with 368 donor iRFP, 251 donor GA175-iRFP, 430 receiver iRFP and 328 GA175-iRFP cells were analyzed. Cells with and without GFP signal were analyzed separately (indicated by +/­­−). White and red arrows indicate cells with cytoplasmic TDP-43 in GFP positive and negative cells, respectively. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
iRFP: 
GA: 203228
TDP-43: 23435"
  },
  {
    "caption": " (F) in addition to filter trap assay of SDS-insoluble TDP-43ΔNLS-GFP aggregates compared in iRFP or GA175-iRFP transfected cells. ",
    "ncbi_link": "iRFP: 
GA: 203228"
  },
  {
    "caption": " (G) GFP mRNA expression levels were measured by qPCR. RNA levels were normalized to GAPDH, β-actin and β2-microglobulin mRNA. Bar-graphs of mean ± SD. Unpaired two-tailed t-test with Welch's correction. * denotes p<0.05, and ** denotes p<0.01. ",
    "ncbi_link": "GFP: 
β-actin: 60
β2-microglobulin: 567
GAPDH: 2597"
  },
  {
    "caption": " (A) Confocal imaging showed anti-GA antibody treatment reduces poly-GA aggregates and TDP-43 mislocalization in hippocampal neurons. White and red arrows show cells with cytoplasmic TDP-43 in GFP-positive and -negative cells, respectively. Scale bar denotes 30 µm. ",
    "ncbi_link": "poly-GA: 203228"
  },
  {
    "caption": " (B) Automated quantification of cells with cytoplasmic TDP-43 in GFP or GA175-GFP transduced (donor), non-transduced (receiver) neurons. Four groups were excluded due to very high GFP transduction rate (GFP-negative donor) and very low GFP transmission rate (GFP-positive receiver with IgG and anti-GA) and complete prevention of GA-RFP transmission of anti-GA immunodepletion (GA-GFP receiver with anti-GA). n=3 biological replicates. In total 280 donor GFP, 284 receiver GFP with IgG, 317 receiver GFP with anti-GA, 277 donor GA175-GFP, 294 receiver GA175-GFP with IgG, 311 receiver GA175-GFP with anti-GA cells were analyzed. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. *** denotes p<0.001. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228"
  },
  {
    "caption": " (D) Poly-GA levels in conditioned media before and after immunodepletion with control IgG and anti-GA antibody were determined by immunoassay. n=3 biological replicates. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ** denotes p<0.01, and *** denotes p<0.001. ",
    "ncbi_link": "Poly-GA: 203228"
  },
  {
    "caption": " Double immunofluorescence of the proteasome subunit PSMC4 and poly-GA inclusions in spinal cord of GA149-CFP transgenic mouse Scale bar denotes 20 µm. ",
    "ncbi_link": "CFP: 
GA: 203228"
  },
  {
    "caption": " Double immunofluorescence of the proteasome subunit PSMC4 and poly-GA inclusions in cortex of C9orf72 patients compared to controls. Scale bar denotes 20 µm. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": " Co-culture model of HeLa cells transfected with iRFP or GA175-iRFP in the donor compartment and an UbG76V-GFP proteostasis reporter in donor and receiver compartment (48 h). (C) Separate analysis of both compartments by immunoblot and (D) immunoblot quantification. For quantitative analysis of immunoblots UbG76V-GFP was normalized to calnexin. n=3 biological replicates. Scatter plot with mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. Red dashed line indicates the control's expression level. * denotes p<0.05, *** denotes p<0.001. ",
    "ncbi_link": "GFP: 
iRFP: 
GA: 203228"
  },
  {
    "caption": " (E) GFP mRNA expression levels were measured by qPCR. RNA levels were normalized to GAPDH, β-actin and β2-microglobulin mRNA. Bar-graphs of mean ± SD. n=3 biological replicates. Unpaired two-tailed t-test with Welch's correction. ",
    "ncbi_link": "GFP: 
β-actin: 60
β2-microglobulin: 567
GAPDH: 2597"
  },
  {
    "caption": " (F,G) Flow cytometry analysis of a UbG76V-GFP reporter cell line incubated 48h with conditioned media from RFP or GA175-RFP transfected cells upon immunodepletion of poly-GA or control depletion using unspecific IgG. n=3 biological replicates. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. * denotes p<0.05. (G) Comparisons of the corresponding histograms for compensated RFP and UbG76V-GFP fluorescence from one representative experiment that shows specific transmission of GA175-RFP associated with accumulation of UbG76V-GFP in cells incubated with GA175-RFP conditioned media. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
poly-GA: 203228"
  },
  {
    "caption": " Primary hippocampal neurons were transduced with GFP or GA175-GFP after 4 days in vitro, incubated for 7 days (DIV 4+7), and treated with vehicle (DMSO), MG132 (10µM) or rolipram (30 µM) for 16h. (A) Immunofluorescence reveals enhanced cytoplasmic TDP-43 levels in neurons with poly-GA aggregates or treated with MG132. Arrows mark punctate TDP-43 staining. Rolipram treatment reduced cytoplasmic TDP-43 in GA175-GFP neurons. Scale bar denotes 20 µm. (B) Automated quantification of cells with cytoplasmic TDP-43 in GFP or GA175-GFP transduced neurons. n=4 biological replicates. In total 462 GFP and 371 GA175-GFP cells treated with vehicle, and 386 GFP and 529 GA175-GFP cells treated with MG132, 513 GFP and 434 GA175-GFP cells treated with rolipram were analyzed. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " Primary hippocampal neurons were transduced with GFP or GA175-GFP after 4 days in vitro, incubated for 7 days (DIV 4+7), and treated with vehicle (DMSO), MG132 (10µM) or rolipram (30 µM) for 16h. (C) Immunoblot to show effects of MG132 and rolipram on GA175-GFP and GFP expression. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " Primary hippocampal neurons were transduced with GFP or GA175-GFP after 4 days in vitro, incubated for 7 days (DIV 4+7), and treated with vehicle (DMSO), MG132 (10µM) or rolipram (30 µM) for 16h. Filter trap assay with quantification of SDS-insoluble aggregated GA175-GFP. n=5 biological replicates. Scatter plot with mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " (F,G) HeLa cells were co-transfected with RFP-TDP-CTF and GFP or GA175-GFP for 2 days. For the final 16h, cells were treated with rolipram (30 µM) or MG132 (10 µM). Filter trap assay of SDS-insoluble TDP-CTF aggregates quantified by densitometry. n=4 biological replicates. Scatter dot plot, mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": " (H,I) HeLa cells were co-transfected with TDP-43ΔNLS-GFP and iRFP or GA175-iRFP for 2 days. For the final 16h, cells were treated with either vehicle or rolipram (30 µM). Filter trap assay of SDS-insoluble TDP-43ΔNLS-GFP aggregates quantified by densitometry. n=3 biological replicates. Scatter dot plot, mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
iRFP: 
GA: 203228
TDP-43: 23435"
  },
  {
    "caption": " Hela cells were co-transfected with an RFP-based TDP-NLS reporter and GFP or GA175-GFP. 24 h after transfection, cells were treated with rolipram (30 µM) for 16h. In the immunofluorescence GFP is not shown because diffuse GFP expression would hide the cytoplasmic RFP-reporter. White arrows indicate cells with cytoplasmic TDP-43. (B) Automated quantification of cells with cytoplasmic TDP-NLS reporter in GFP and GA175-GFP positive cells. n=4 biological replicates. In total 345 GFP and 386 GA175-GFP cells treated with vehicle, 371 GFP and 404 GA175-GFP cells treated with rolipram were analyzed. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": " Hela cells were co-transfected with an RFP-based TDP-NLS reporter and GFP or GA175-GFP. 24 h after transfection, cells were treated with rolipram (30 µM) for 16h. (C) RFP-NLSTDPWT mRNA expression levels were measured by qPCR. n=3 biological replicates. Bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": " Hela cells were co-transfected with the RFP-based TDP-NLS reporter, GFP or GA175-GFP, as well as PSMD11 or empty vector. Image analysis as in (A). n=4 biological replicates. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. 354 GFP and 330 GA175-GFP cells with vector, 367 GFP and 369 GA175-GFP cells with PSMD11 in total were analyzed. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
PSMD11: 5717"
  },
  {
    "caption": " Hela cells were co-transfected with the RFP-based TDP-NLS reporter, GFP or GA175-GFP, as well as PSMD11 or empty vector. F) RFP-NLSTDPWT mRNA expression levels were measured by qPCR. n=3 biological replicates. Bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "GFP: 
RFP: 
GA: 203228
PSMD11: 5717
TDP: 23435"
  },
  {
    "caption": " Immunofluorescence of Hela cells transfected with GFP or GA175-GFP showing reduced poly-GA aggregation upon rolipram treatment (30 µM, 16 h). (H) Automated quantification of poly-GA aggregate number per cell. n=3 biological replicates. In total 223 cells treated with vehicle and 286 cells treated with rolipram were analyzed. Scatter plot with bar-graphs of mean ± SD. Unpaired two-tailed t-test with Welch's correction. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " (I) GA-GFP mRNA expression levels were measured by qPCR. n=3 biological replicates. Bar-graphs of mean ± SD. Unpaired two-tailed t-test with Welch's correction. ",
    "ncbi_link": "GFP: 
GA: 203228"
  },
  {
    "caption": " (B) Immunoblot of HeLa cells transfected with RFP-based TDP-NLS wild-type (WT) or mutants (K84A, K84R, K95A, K95R). ",
    "ncbi_link": "RFP: 
TDP: 23435"
  },
  {
    "caption": " (C HeLa cells were co-transfected with the indicated TDP-NLS reporters as well as GFP or GA175-GFP, and treated with MG132 (10µM) or vehicle for 16h. ",
    "ncbi_link": "GFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": " (D) Automated quantification of RFP-NLS reporters in GFP positive cells. Note that K84A and K84R block overall import, while K95A and K95R allow import but are resistant to inhibition by poly-GA. n=4 biological replicates. The total number of cells analyzed per group was (from left to right): 667, 581, 789, 783, 809, 708, 628, 721, 938, 557, 857, 861, 886, 699,789, 539, 636, 577, 638 and 870. Scatter plot with bar-graphs of mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. *** denotes p<0.001. Scale bar denotes 20 µm. ",
    "ncbi_link": "GFP: 
RFP: 
poly-GA: 203228"
  },
  {
    "caption": " (E,F) HeLa cells were co-transfected with the indicated GFP-TDP NLS reporters and iRFP or GA175-iRFP. Cell lysates were immunoprecipitated with anti-GFP and immunoblotted with indicated antibodies to detect co-immunoprecipitation of the TDP-43 NLS with importin-α5/KPNA1 nuclear import receptor. (F) Quantification of KPNA1 levels normalized to total GFP-NLSTDP reporter levels in anti-GFP immunoprecipitates. n=3 biological replicates. Scatter plot with mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. *** denotes p<0.001. See also Figure EV4. Red dashed line indicates the control's expression level. ",
    "ncbi_link": "GFP: 
iRFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": " HeLa cells were co-transfected with wildtype or K95A GFP-TDP NLS, HA-ubiquitin and iRFP or GA175-iRFP. 24h after transfection, cells were treated with rolipram (30 µM), MG132 (10 µM) or DMSO (vehicle) for 16h. Lysates were immunoprecipitated with Protein G beads coupled with anti-GFP antibody. (A) Immunoblotting of input (left panels) and anti-GFP immunoprecipitates (right panels) to show GFP-reporter levels and poly-ubiquitination. (B) Quantification of HA-ubiquitin levels normalized to total GFP- NLSTDP reporter levels in anti-GFP immunoprecipitates. n=3 biological replicates. Scatter plot, mean ± SD. One-way ANOVA with Tukey's multiple comparisons test. * denotes p<0.05, and *** denotes p<0.001. Red dashed line indicates the control's expression level. ",
    "ncbi_link": "GFP: 
HA: 
iRFP: 
GA: 203228
TDP: 23435"
  },
  {
    "caption": "B WB  showing depletion of PERK  in Perk  KO astrocytes  and neurons.",
    "ncbi_link": "Perk: 13666"
  },
  {
    "caption": "D-I eIF2α phosphorylation  in WT and Perk  KO astrocytes  (N=3) and neurons  (N=6) ± 20-24 hours of TM-induced ER  stress. Representative WB  (D, G), quantification of absolute phosphorylated eIF2α  level (p-eIF2α/eIF2α) (E, H) and the ER  stress-induced p-eIf2α  response (F, I). Data information: (E, H, Data are normalised to untreated WT. (F, I Data are related to untreated cells of the same genotype. Baseline level (without ER  stress) is depicted by a dashed line. Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: ** P<0.01, *** P<0.001, **** P<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (E, H, Students t-test (F, I)",
    "ncbi_link": "Perk: 13666"
  },
  {
    "caption": "J-O Protein synthesis in WT and Perk  KO astrocytes  (N=5) and neurons  (N=5) ± 20-24 hours of TM-induced ER  stress. Representative images obtained by high-content microscopy  showing puromycinilated proteins detected by immunofluorescence  (J, M), quantification of puromycin  intensity as measure for de novo protein synthesis (K, N) and the ER  stress-induced protein synthesis response (L, O). Astrocytic soma  (GFAP, white), dendrites  (MAP2, white), nuclei  ((Δ)Cre, red), de novo synthesized proteins (Puromycin, green). Scale bar: 25 μm. Data information: K, N) Data are normalised to untreated WT. , L, O) Data are related to untreated cells of the same genotype. Baseline level (without ER  stress) is depicted by a dashed line. Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: ** P<0.01, *** P<0.001, **** P<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test K , N); Nested t-test (L, O).",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "A-F ATF4 expression   in WT and Perk  KO astrocytes  (N=3) and neurons  (N=9) ± 20-24 hours of TM-induced ER  stress. (A, D) Representative confocal  images of ATF4 immunofluorescence. Astrocytic soma  (GFAP, cyan), dendrites  (MAP2, cyan), nuclei  ((Δ)Cre, green), ATF4  (magenta). Scale bar: 10 μm. (B, E) Quantification of absolute nuclear ATF4  intensity. Data are normalised to untreated WT. (C, F) Quantification of the ER  stress-induced ATF4 response. Data are related to untreated cells of the same genotype. Baseline level (without ER  stress) is depicted by a dashed line. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant p-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (B, E); Nested t-test (C, F).",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "G-J (G, I) Venn diagram showing the number of significantly upregulated ATF4  target genes in WT (grey and blue) and Perk  KO (green and blue) astrocytes  (G, N=3) and neurons  (I, N=3) upon 20-24 hours of TM-induced ER  stress determined by mRNA-seq. Percentage: fraction of upregulated ATF4  target genes in WT cells that are also upregulated in Perk  KO cells. (H, N=3; J, N=3) Log2 fold change of ATF4  target genes that are significantly upregulated in both WT and Perk  KO cells (blue in Venn diagram). Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant p-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant.",
    "ncbi_link": "Perk: 13666"
  },
  {
    "caption": "Protein synthesis and ATF4 expression  in mouse  (A-F) astrocytes  (A-C and neurons  (D-F ± 20-24 hours of TM-induced ER  stress ± PERK-i (Pi). (A, D, Representative images obtained by  high-content microscopy. Astrocytic soma  (GFAP dendrites  (MAP2, white), nuclei  (ΔCre, red), de novo synthesized proteins (Puromycin, green), ATF4  (magenta). Scale bar: 25 μm. (B, N=5; E, N=5; Quantification of puromycin  intensity as measure for de novo protein synthesis. (C, N=5; F, N=7; Quantification of absolute nuclear ATF4  intensity. Data information: Data are normalised to untreated WT and presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *** p<0.001, **** p<0.0001. Statistical analysis: Two-way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Protein synthesis and ATF4 expression  in human  (G-L) astrocytes  G-I, ) and neurons  J-L) ± 20-24 hours of TM-induced ER  stress ± PERK-i (Pi). G, J) Representative images obtained by high-content microscopy. Astrocytic soma Phalloidin, white), dendrites  (MAP2, white), nuclei  (ΔCre, red), de novo synthesized proteins (Puromycin, green), ATF4  (magenta). Scale bar: 25 μm. ; H, N=3; K, N=3) Quantification of puromycin  intensity as measure for de novo protein synthesis. I, N=4; L, N=3) Quantification of absolute nuclear ATF4  intensity. Data information: Data are normalised to untreated WT and presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *** p<0.001, **** p<0.0001. Statistical analysis: Two-way ANOVA with Tukey's post hoc test.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "D-G ROS  accumulation in WT and Perk KO neurons (N=3) and astrocytes  (N=3) ± 20-24 hours of TM-induced ER  stress. (D, F) Representative images obtained by high-content microscopy. Dendrites   (MAP2, white), astrocytic soma  (Phalloidin, white), nuclei ((Δ)Cre, red), ROS  (CellROX  green, green). Scale bar: 25 μm. (E, G) Quantification of CellROX  green intensity. Data information: (E, G, Data are normalised to untreated WT. Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (E, G,",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "H mRNA expression of Eif2ak1  (HRI) in HRI  KD neurons  determined by RT-qPCR, normalised to WT transduced with shRNA control (represented by a dashed line) (N=3). Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis One sample t-test with a hypothetical value of 100 (H",
    "ncbi_link": "Eif2ak1: 15467
HRI: 15467"
  },
  {
    "caption": "I Quantification of the increase in nuclear ATF4  intensity in WT neurons  ± HRI  KD ± 20 hours of sodium arsenite  (Ars) treatment (N=3). J The remaining ATF4  response (%) upon HRI  KD, related to ATF4  response of WT transduced with shRNA control (100%, represented by a dashed line) (N=3). Calculated from data in (I): [[(KD_Ars+-KD_Ars-)/KD_Ars-]/[(WT_Ars+-WT_Ars-)/WT_Ars-]]*100. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test I, One sample t-test with a hypothetical value of 100 J)",
    "ncbi_link": "HRI: 15467"
  },
  {
    "caption": "K-M eIF2α phosphorylation in HRI  KD WT and Perk  KO neurons (N=3) ± 20-24 hours of TM-induced ER  stress. Representative WB  (K), quantification of the ER  stress-induced p-eIf2α  response (L) and absolute phosphorylated eIF2α  level (p-eIF2α/eIF2α) (M). Data information: M, Data are normalised to untreated WT. (L, Data are related to untreated cells of the same genotype and normalised to WT without HRI  KD. Baseline level (without ER stress) is depicted by a dashed line. Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test L, Students t-test (M)",
    "ncbi_link": "HRI: 15467
Perk: 13666"
  },
  {
    "caption": "N-S Protein synthesis (N=3) and ATF4 expression  (N=4) in HRI  KD WT and Perk  KO neurons  ± 20-24 hours of TM-induced ER  stress. Representative images obtained by (N) confocal  and (Q)  high-content microscopy. Dendrites  (MAP2, white/cyan), nuclei  ((Δ)Cre, green/red), de novo synthesized proteins (Puromycin, green), ATF4  (magenta). Scale bar: 25 μm. Quantification of the ER  stress-induced protein synthesis  response (O) and puromycin intensity as measure for de novo protein synthesis (P). Quantification of the ER  stress-induced ATF4  response (R) and absolute nuclear ATF4  intensity (S). Data information: P, S) Data are normalised to untreated WT. O, R) Data are related to untreated cells of the same genotype and normalised to WT without HRI  KD. Baseline level (without ER  stress) is depicted by a dashed line. Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test O, R); Nested t-test (P, S).",
    "ncbi_link": "Cre: 2777477
HRI: 15467
Perk: 13666"
  },
  {
    "caption": "A-F Protein synthesis (A-C, N=3) and ATF4 expression  (D-F, N=5) in WT and Perk  KO neurons  overexpressing eIF2αWT or phospho-deficient eIF2αS51A ± 20-24 hours of TM-induced ER  stress. Representative images obtained by (A) confocal  and (D)  high-content microscopy. Dendrites  (MAP2, white/cyan), nuclei  ((Δ)Cre, red), de novo synthesized proteins (Puromycin, green), ATF4  (magenta). Scale bar: 25 μm. Quantification of the ER  stress-induced protein synthesis (B) and ATF4  response (E). Data are normalised to WT eIF2αWT. Quantification showing the percentage change in the ER  stress-induced protein synthesis (C) and ATF4  (F) response induced by eIF2αS51A compared to eIF2αWT. (C) Calculated from data in (B): [(eIF2αS51A-eIF2αWT)/eIF2αWT] *100. (F) Calculated from data in (E): [(eIF2αS51A-eIF2αWT)/eIF2αWT]*-100. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *** p<0.001, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (B, E, Nested t-test (C, F).",
    "ncbi_link": "Cre: 2777477
eIF2α: 83939
Perk: 13666"
  },
  {
    "caption": "Expression   of p-eIF2α  sensitive (5'ATF4-uORFWT) and p-eIf2α   insensitive (5'ATF4-uORFMut) EYFP translational reporters in WT and Perk  KO neurons  ± 20-24 hours of TM-induced ER  stress (N=3). (I, K) Representative confocal  images. Dendrites  (MAP2, cyan), nuclei  ((Δ)Cre, red), endogenous ATF4  (magenta), ATF4  reporter (green). Scale bar: 10 μm. (J, L) Quantification of EYFP  intensity, normalised to untreated WT. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *** p<0.001, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test J, L)",
    "ncbi_link": "EYFP: 
ATF4: 468
Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "A-F  Protein synthesis and ATF4 expression  in ISRIB-treated WT and Perk  KO neurons  ± 20-24 hours of TM-induced ER  stress (N=4). (A, D) Representative images obtained by high-content microscopy. Dendrites  (MAP2, white), nuclei ((Δ)Cre, red), de novo synthesized proteins (Puromycin, green), ATF4  (magenta). Scale bar: 25 μm. Quantification of the ER  stress-induced protein synthesis (B) and ATF4  (E) response. Data are normalised to WT without ISRIB. Baseline level (without ER  stress) is depicted by dashed line. Quantification showing the percentage change in the ER  stress-induced protein synthesis (C) and ATF4  (F) response induced by ISRIB. (C) Calculated from data in (B): [(ISRIB+-ISRIB-)/ISRIB-]*100. (F) Calculated from data in (E): [(ISRIB+-ISRIB-)/ISRIB-]*-100. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, *** p<0.001, **** p<0.0001 and ns: not significant. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (B, E); Nested t-test (C, F)",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "A Differentially expressed genes (DEGs) involved in oxidative stress related processes comparing TM-treated Perk  KO and WT neurons. Blue arrow: Ang.",
    "ncbi_link": "Ang: 11727
Perk: 13666"
  },
  {
    "caption": "B, C Ang  mRNA level in WT and Perk  KO neurons  and astrocytes  ± 20-24 hours of TM-induced ER  stress, determined by mRNA-seq (N=3). FPMK: Fragments Per Kilobase of transcript per Million. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Statistical analysis: Two-way ANOVA with Tukey's post hoc test (B, C,",
    "ncbi_link": "Ang: 11727
Perk: 13666"
  },
  {
    "caption": "F, G tRNA  unfolding in WT and Perk  KO neurons  ± 20-24 hours of TM-induced ER  stress (N=4). (F) Representative images obtained by  high-content microscopy   of 1-methyladenosine (m1A) immunofluorescence  to determine tRNA  unfolding. Dendrites  (MAP2, white), nuclei  ((Δ)Cre, red), unfolded tRNA  (m1A, green). Scale bar: 25 μm. (G) Quantification of m1A  intensity, normalised to untreated WT. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Statistical analysis: Two-way ANOVA with Tukey's post hoc test G,",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "H-M Abundance of small RNAs in WT and Perk  KO astrocytes  (N=3) and neurons  (N=6) ± 20-24 hours of TM-induced ER  stress, determined by high-resolution automated electrophoresis  (H, K) Representative gel image. Electropherogram  (I, L) and zoom (J, M) showing quantified fluorescence units (FU) of  small RNAs, size ranges of  tRNAs and tsncRNAs  are indicated. Shown is the mean of the biological replicates.",
    "ncbi_link": "Perk: 13666"
  },
  {
    "caption": "N-R Protein synthesis  and ATF4 expression  in WT and Perk  KO neurons  ± 20-24 hours of TM-induced ER  stress in the presence or absence of ANG-I (N=3). (N) Representative images obtained by  high-content microscopy. Dendrites  (MAP2, white), nuclei  ((Δ)Cre, red), de novo synthesis of proteins (Puromycin, green). Scale bar: 25 μm. Quantification of the ER  stress-induced protein synthesis (O) and ATF4  response (Q). Data are normalised to WT without ANG-i. Baseline level (without ER  stress) is depicted by dashed line. Quantification showing the percentage change in the ER  stress-induced protein synthesis (P) and ATF4  response (R) induced by ANG-i. (P) Calculated from data in (O): [(ANG-i+-ANG-i-)/ANG-i-]*100. (R) Calculated from data in (Q): [(ANG-i+-ANG-i-)/ANG-i-]*-100. Data information: Data are presented as mean ± SEM. N: Biological replicate. Relevant P-values are indicated: *p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Statistical analysis: Two-way ANOVA with Tukey's post hoc test O, Q); Nested t-test (P, R).",
    "ncbi_link": "Cre: 2777477
Perk: 13666"
  },
  {
    "caption": "A  PHIP-1 interaction  with GPB-1 by  yeast two-hybrid assay. The reporter strain PJ69-4A was co-transformed with expression vectors encoding GAL4  DBD-PHIP-1(H45A) and GAL4  AD-GPB-1, as indicated. Yeast  strains carrying the indicated plasmids were cultured on a selective plate lacking histidine  and containing 5 mM 5-aminotriazole for 4 days.",
    "ncbi_link": "GAL4: 855828
GPB-1: 174803
PHIP-1: 185336"
  },
  {
    "caption": "A His-phosphorylation  of GPB-1 in animals. The  phip-1(km96) mutant animals carrying the 3XFLAG::gpb-1 or 3XFLAG::gpb-1(H266F) knock-in allele were lysed. The lysates were treated with or without heating  (95°C) and immunoblotted  (IB) with anti-3-pHis and anti-FLAG  antibodies.",
    "ncbi_link": "FLAG: 
gpb-1: 174803
phip-1: 185336"
  },
  {
    "caption": "B  NDK-1 phosphorylates GPB-1 in vitro. COS-7 cells were co-transfected with HA-GPB-1 or HA-GPB-1(H266F) and T7-GPC-2, and cell lysates were immunoprecipitated  (IP) with anti-HA  antibodies. Immunopurified GPB-1 was subjected to the in vitro  kinase assay with recombinant GST-NDK-1. Phosphorylated GPB-1  was detected by immunoblotting  (IB) with anti-3-pHis antibodies.",
    "ncbi_link": "HA: 
T7: 
GPB-1: 174803
GPC-2: 172396"
  },
  {
    "caption": "C PHIP-1 dephosphorylates GPB-1 in vitro. COS-7 cells were co-transfected with HA-GPB-1 and T7-GPC-2, and cell lysates were immunoprecipitated  (IP) with anti-HA  antibodies. The immunopurified HA-GPB-1 was first subjected to the in vitro  kinase assay  with recombinant GST-NDK-1. Phosphorylated GPB-1 was then equally aliquoted and subjected to the in vitro phosphatase assay  with recombinant GST-PHIP-1 or its variants. Phosphorylated GPB-1 was detected by immunoblotting  (IB) with anti-3-pHis antibodies.",
    "ncbi_link": "HA: 
GPB-1: 174803
GPC-2: 172396"
  },
  {
    "caption": "A  PHIP-1 interaction  with   UNC-51  by yeast two-hybrid assay. The reporter strain PJ69-4A was co-transformed with expression vectors encoding GAL4  DBD-PHIP-1(H45A) and GAL4  AD-UNC-51(274-856), as indicated. Yeast  strains carrying the indicated plasmids were cultured on a selective plate lacking histidine  and containing 5 mM 5-aminotriazole for 4 days.",
    "ncbi_link": "GAL4: 855828
PHIP-1: 185336
UNC-51: 180311"
  },
  {
    "caption": "C UNC-51 phosphorylates PHIP-1 at Ser-112. COS-7  cells were co-transfected with Flag-PHIP-1 (WT or mutants) and GFP-UNC-51 [WT or ∆AIKAI (KD)], and cell lysates were analyzed using Phos-tag  SDS-PAGE. Total lysates were immunoblotted  (IB) with antibodies, as indicated. Filled and open arrowheads indicate unmodified and phosphorylated PHIP-1, respectively. Asterisk indicates non-specific band.",
    "ncbi_link": "Flag: 
GFP: 
PHIP-1: 185336
UNC-51: 180311"
  },
  {
    "caption": "C) Representative cases show the first and fourth generation xenograft H&E staining (left) and EBER-1 ISH staining (right).",
    "ncbi_link": "EBER-1: "
  },
  {
    "caption": "Expression of stemness markers (Sox2, Klf4, Bmi1, Oct4) and drug resistance genes (ABCG2, Mrp1) evaluated by real-time PCR (G) in SNU719 and SNU-4th cells.",
    "ncbi_link": "Mrp1: 4363
ABCG2: 9429
Bmi1: 648
Klf4: 9314
Oct4: 5460
Sox2: 6657"
  },
  {
    "caption": "I) Real-time PCR analysis of the expression of EMT-associated markers (E-cad, vimentin) and transcription factors (Twist1, Snail, Slug, Zeb1) in SNU719 and SNU-4th cells.",
    "ncbi_link": "E-cad: 999
Snail: 6615
Slug: 6591
Twist1: 7291
vimentin: 7431
Zeb1: 6935"
  },
  {
    "caption": "(B) Real-time PCR analysis of the expression of circLMP2A in SNU-4th, SNU719 and YCCEL1 cells.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(C) The existence of circLMP2A was validated by RT-PCR (up) and real-time PCR (down) in SNU-4th, SNU719 and YCCEL1 cells treated with or without RNase R digestion. GAPDH was used as a negative control.",
    "ncbi_link": "circLMP2A: 
GAPDH: "
  },
  {
    "caption": "(D) Real-time PCR analysis of circLMP2A and LMP2A expression after treatment with actinomycin D at the indicated time points in SNU-4th cells.",
    "ncbi_link": "circLMP2A: 
LMP2A: 3783751"
  },
  {
    "caption": "(E) Real-time PCR analysis of circLMP2A and LMP2A expression in either the cytoplasm or nucleus in SNU-4th cells. GAPDH and U6 were used as controls in cytoplasm and nucleus, respectively.",
    "ncbi_link": "circLMP2A: 
GAPDH: 
U6: 
LMP2A: 3783751"
  },
  {
    "caption": "(F) RNA ISH for circLMP2A. U6 and 18S are mainly localized in the nucleus and cytoplasm, respectively, and were used as controls.",
    "ncbi_link": "18S: 
circLMP2A: 
U6: "
  },
  {
    "caption": "(G) Kaplan-Meier survival curve analysis showing the correlation between circLMP2A expression and OS. n= 69, P < 0.001, log-rank test. (H) Kaplan-Meier survival curve analysis showing the correlation between circLMP2A expression and progression-free survival (PFS). n = 69, P < 0.001, log-rank test. ",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(A) Real-time PCR analysis of the interfering efficacy and linear LMP2A mRNA levels after transfection of three circLMP2A shRNAs.",
    "ncbi_link": "circLMP2A: 
LMP2A: 3783751"
  },
  {
    "caption": "(B) Tumour sphere culture analysis of the tumour sphere formation in SNU-4th cells transfected with sh-circLMP2A-2, sh-circLMP2A-3 or sh-control. The central horizontal lines represent the median, top and bottom positions of the box represent upper and lower quartiles, and error bars represent the mean ± SD. The average number and maximal diameter of spheres were calculated under a microscope in five randomly chosen fields in each independent experiment, n=3 biological replicates. Scale bars =100µm.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "EMT-related markers, stemness markers and drug resistance genes were evaluated by real-time PCR (C) in SNU-4th cells transfected with sh-circLMP2A-2, sh-circLMP2A-3 or sh-control.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "EMT-related markers, stemness markers and drug resistance genes were evaluated by WB (D) in SNU-4th cells transfected with sh-circLMP2A-2, sh-circLMP2A-3 or sh-control.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(E-F) Transwell assay (E) and colony formation assay (F) analysis of the migratory and invasive capability and colony-forming ability in SNU-4th cells transfected with sh-circLMP2A-2, sh-circLMP2A-3 or sh-control. Scale bars =100µm.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(G-H) Flow cytometric analysis of the rate of SP cells (G) and apoptosis (H) in SNU-4th cells transfected with sh-circLMP2A-2, sh-circLMP2A-3 or sh-control.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "Subcutaneously established tumour xenografts in NOD/SCID mice. Tumour volume (I) of the xenografts were remarkably inhibited by down-regulation of circLMP2A. Six mice per group.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "Subcutaneously established tumour xenografts in NOD/SCID mice. tumour weight (J) of the xenografts were remarkably inhibited by down-regulation of circLMP2A. Six mice per group.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(A) Real-time PCR confirmed the over-expression of circLMP2A in SNU719 and YCCEL1 cells after transfection.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(B) Over-expression of circLMP2A induced the formation of tumour spheres in SNU719 and YCCEL1 cells. The central horizontal lines represent the median, top and bottom positions of the box represent upper and lower quartiles, and error bars represent the mean ± SD. The average number and maximal diameter of spheres were calculated under a microscope in five randomly chosen fields in each independent experiment, n=3 biological replicates. Scale bars =100µm.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "EMT-related markers, stemness markers and drug resistance genes were assessed by real-time PCR (C) in SNU719 and YCCEL1 cells transfected with circLMP2A or vector.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "EMT-related markers, stemness markers and drug resistance genes were assessed by WB (D) in SNU719 and YCCEL1 cells transfected with circLMP2A or vector.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(E-F) Flow cytometric analysis of the rate of SP cells (E) and apoptosis (F) in SNU719 and YCCEL1 cells transfected with circLMP2A or vector.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(G-H) Transwell assay (G) and colony formation assay (H) analysis of the migratory and invasive capability and colony-forming ability in SNU719 and YCCEL1 cells transfected with circLMP2A or vector. Scale bars =100µm.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "Subcutaneously established tumour xenografts in NOD/SCID mice. Tumour volume (I) of the xenografts were significantly increased by over-expression of circLMP2A. Six mice per group.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "Subcutaneously established tumour xenografts in NOD/SCID mice. tumour weight (J) of the xenografts were significantly increased by over-expression of circLMP2A. Six mice per group.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(C-E) Real-time PCR analysis of 7 miRNA expression in SNU-4th cells transfected with sh-circLMP2A-2 or sh-control (C), and SNU719 (D) and YCCEL1 cells (E) transfected with circLMP2A or vector.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(F-H) circ LMP2Ain specific probe and detected by real-time PCR (F) and RT-PCR (H). The relative levels of 5 miRNA candidates were detected by real-time PCR (G) and RT-PCR (H). GAPDH was used as a negative control.",
    "ncbi_link": "circLMP2A: 
GAPDH: "
  },
  {
    "caption": "(I) RNA ISH showing the co-localization between circLMP2A and miR-3908 in SNU-4th cells. circLMP2A probes were labelled with Cy3, and miR-3908 probes were labelled with FITC. Nuclei were stained with DAPI.",
    "ncbi_link": "circLMP2A: 
miR-3908: 100500909"
  },
  {
    "caption": "(K) Dual luciferase reporter assay for luciferase activity of the indicated plasmids (circLMP2A Wt, circLMP2A mut1, circLMP2A mut2, circLMP2Amut3 luciferase reporter) in HEK-293T cells transfected with mimic-NC or miR-3908.",
    "ncbi_link": "circLMP2A: 
miR-3908: 100500909"
  },
  {
    "caption": "(H) Pearson correlation analysis of the correlation between the expression of circLMP2A and miR-3908. n = 69, P = 0.039, Pearson's correlation coefficient analysis.",
    "ncbi_link": "circLMP2A: 
miR-3908: 100500909"
  },
  {
    "caption": "(I) Kaplan-Meier survival curves analysis of the correlation between miR-3908 expression and OS. n = 69, P = 0.049, log-rank test.",
    "ncbi_link": "miR-3908: 100500909"
  },
  {
    "caption": "(B) Dual luciferase reporter assay for the luciferase activity of the indicated plasmids (TRIM59-Wt and TRIM59-Mut luciferase reporter) in HEK-293T cells transfected with mimic-NC or miR-3908.",
    "ncbi_link": "miR-3908: 100500909
TRIM59: 286827"
  },
  {
    "caption": "(C) Real-time PCR analysis of the mRNA level of TRIM59 in SNU719 and SNU-4th cells.",
    "ncbi_link": "TRIM59: 286827"
  },
  {
    "caption": "(D-F) Real-time PCR analysis of the expression of TRIM59 in SNU-4th (D), SNU719 (E) and YCCEL1 cells (F) transfected with the above different mimics.",
    "ncbi_link": "TRIM59: 286827"
  },
  {
    "caption": "(J) Immunohistochemical staining showing that over-expression of circLMP2A could lead to increased expression of TRIM59 and ERG but decreased expression of p53.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "(L)Immunohistochemical staining showing that high expression of circLMP2A in EBVaGC tissues resulted in significant increases in CD44+ CD24- cells and significant decreases in p53+ cells.",
    "ncbi_link": "circLMP2A: "
  },
  {
    "caption": "A. Size of adult (9-14 week) CEP250+/+ and CEP250-/- mice. B. Body weight of CEP250+/+ and CEP250-/- mice (9-14 week). CEP250+/+ n=5 mice, CEP250-/- n=5 mice. Data information: In (B , data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test). In (B whiskers represent the range of the data, with bottom and top represent min and max value of the dataset respectively.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "C. Brains from adult CEP250+/+ and CEP250-/- mice (9-14 week). Scale bars: 1000 µm. D. Brain weight of 9-14-week-old mice. CEP250+/+ n=5 mice, CEP250-/- n=5 mice. Data information: In data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test). In whiskers represent the range of the data, with bottom and top represent min and max value of the dataset respectively.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "F. Adult testis (9-14 week) of CEP250+/+ and CEP250-/- mice. Scale bars: 1000 µm. G. Adult testis (9-14 week) weight of CEP250+/+ and CEP250-/- mice. CEP250+/+ n=10 mice, CEP250-/- n=10 mice. Data information: In data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test). In G) whiskers represent the range of the data, with bottom and top represent min and max value of the dataset respectively.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "K. Bright-field image of live epididymal sperm from CEP250+/+ and CEP250-/- mice (9-14 week). Scale bars: 10 µm. Arrow heads highlight the sperm heads. L. Quantification of (K), sperm number per mouse. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. Data information: In data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "N. Immunofluorescence for GATA4 (green) with DAPI staining (blue) of 10 µm testis cryo-sections from adult CEP250+/+ and CEP250-/- mice (9-14 week). Scale bars: 100 µm. Dashed lines highlight the STs. O. Quantification of (N), CEP250+/+ n=3 mice, CEP250-/- n=3 mice. 50 STs were analyzed for each mouse. See Appendix Fig S2 for ST number per section and ST diameter. Data information: In O), data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "D. Immunofluorescence for MVH (green) with DAPI staining (blue) of 10 µm testis cryo-sections from neonatal mice (P5, P10 and P14) CEP250+/+ and CEP250-/-. Scale bars: 20 µm.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "E. Quantification of CEP250+/+ n=3 mice, CEP250-/- n=3 mice. Data information: E), data are presented as mean ± SEM. n.s., not significant, **P < 0.01, ****P < 0.0001 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "F. Quantification of C-CASP3 positive cells normalized to total cell number per seminiferous tubule (ST). Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice. 30 STs were analyzed for each mouse. Data information: In (F data are presented as mean ± SEM. n.s., not significant, ***P < 0.005 , ****P < 0.0001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "G. C-CASP3 (green) and MVH (magenta) staining with DAPI (blue) of 10 µm testis cryo-sections from neonatal mice (P5, P10 and P14) CEP250+/+ and CEP250-/-, scale bars: 20 µm. H. Quantification of (G). Percentage of C-CASP3 and MVH double positive cells in relation to total C-CASP3 positive cells per ST from P5, P10 and P14 mice. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice. 30 STs were analyzed for each mouse. I. Quantification of (G). Percentage of C-CASP3 and MVH double positive cells in relation to total MVH positive cells (germ cells) per ST from P5, P10 and P14 mice. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice. 30 STs were analyzed for each mouse. Data information In H, I), data are presented as mean ± SEM. n.s., not significant, ***P < 0.005 , ****P < 0.0001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "A. Immunofluorescence staining for PLZF (red) with DAPI staining (blue) of 10 µm cryo-sections of testes from CEP250+/+ and CEP250-/- mice at P5, P10 and P14. Scale bars: 20 μm.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "B. Quantification of PLZF+ cells per seminiferous (ST) section of CEP250+/+ and CEP250-/-, testes at P5, P10 and P14. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ (P5) n=3 mice, CEP250-/- (P5) n=3 mice, 50 STs were analyzed for each mouse; CEP250+/+ (P10) n=3 mice, CEP250-/- (P10) n=3 mice, at least 30 STs were analyzed for each mouse; CEP250+/+ (P14) n=3 mice, CEP250-/- (P14) n=3 mice, at least 50 ST were analyzed for each mouse. Data information: In (B data are presented as mean ± SEM. n.s., not significant, *P<0.05, ***P < 0.005, ****P < 0.0001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "C. Immunofluorescence staining for SCP1 (green), PLZF (red) and DAPI (blue) of 10 µm cryo-sections of testes from CEP250+/+ and CEP250-/- mice at P2, P3, P5 and P7. Arrowheads highlight PLZF- SCP1+ (green) cells, which represent differentiated spermatogonia. Scale bars: 20 μm.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "Quantification of The number of PLZF+ SCP1-, PLZF+ SCP1+, PLZF- SCP1+ cells normalized to total cell number per ST section in CEP250+/+ and CEP250-/- testes at P2, P3 respectively. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice, at least 40 STs were analyzed for each mouse. Data information: data are presented as mean ± SEM. n.s., not significant, *P<0.05, ***P < 0.005, ****P < 0.0001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "Quantification of The number of PLZF+ SCP1-, PLZF+ SCP1+, PLZF- SCP1+ cells normalized to total cell number per ST section in CEP250+/+ and CEP250-/- testes at , P5 and P7 respectively. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice, at least 40 STs were analyzed for each mouse. Data information: data are presented as mean ± SEM. n.s., not significant, *P<0.05, ***P < 0.005, ****P < 0.0001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "B. Representative images of mouse seminiferous tubule (ST) sections stained for PLZF (red), SCP1 (green) and DAPI (blue) at P4, P6 and P7. Scale bars: 20 μm. Arrowheads highlight PLZF- SCP1+ (green) cells localize to the middle of the ST lumen, which represent differentiated spermatogonia that translocated to the middle of the ST lumen. C. Quantification of (B). Shown is the number of PLZF- SCP1+ cells which translocated inwards the seminiferous tubule lumen per seminiferous tubule section, as normalized to the total cell number per ST section. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice, at least 30 STs were analyzed for each mouse. D. Quantification of (B). Shown is the total number of SCP1+ cells which translocated inwards the seminiferous tubule lumen per ST section, as normalized to the total cell number per seminiferous tubule section. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice, at least 30 STs were analyzed for each mouse. E. Quantification of (B). Shown is the number of PLZF+ SCP1+ cells which translocated inwards the seminiferous tubule lumen per seminiferous tubule section, as normalized to the total cell number per seminiferous tubule section. Dots (colors reflect STs from different mice) represent value per ST, CEP250+/+ n=3 mice, CEP250-/- n=3 mice, at least 30 STs were analyzed for each mouse. Data information: In (C-E), data are presented as mean ± SEM. n.s., not significant, *P<0.05, **P < 0.01, ***P < 0.005 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "A. Representative images of P4 mouse seminiferous tubule (ST) 10 µm cryo-sections stained for PLZF (red), γ-Tubulin (green), PH3 (magenta) and DAPI (blue). Arrowheads highlight the centrosomes. Dashed yellow line highlights the basement membrane. Semi-transparent white line, which bisects both spindle poles was used to determine spindle angle Ø orientation in relation to the basement membrane. Anaphase cells were analyzed. Scale bars: 5 µm. B. Representative images of P5 mouse seminiferous tubule 10 µm cryo-sections stained for PLZF (red), γ-Tubulin (green), PH3 (magenta) and DAPI (blue). Arrowheads highlight the centrosomes. Dashed yellow line highlights the basement membrane. Semi-transparent white line, which bisects both spindle poles was used to determine spindle angle Ø orientation in relation to the basement membrane. Anaphase cells were analyzed. Scale bars: 5 µm. (C Quantitation of spindle angle of anaphase GSCs in P4 ST sections (from A). Spindle angle relative to basement membrane for CEP250+/+ and CEP250-/-). In (C), dots (colors reflect different mice) represent spindle angle of each GSC. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 10 cells were analyzed for each mouse. (D Quantitation of spindle angle of anaphase GSCs in P5 ST sections (from B). for P5. In (D), dots (colors reflect different mice) represent spindle angle of each GSC. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 10 cells were analyzed in each mouse.",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "E) Quantitation of spindle angle of anaphase GSCs in P4 ST sections Spindle angle relative to basement membrane for CEP250+/+ and CEP250-/-). In (E), the three dots represent averaged spindle angle per mouse. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 10 cells were analyzed for each mouse. F) Quantitation of spindle angle of anaphase GSCs in P5 ST sections for P5. In (F), the three dots represent averaged spindle angle per mouse. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 10 cells were analyzed in each mouse. Data information: In (E, F), data are presented as mean ± SEM. n.s., not significant, *P<0.05, ***P < 0.005 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "B. Representative images of P5 mouse ST. 10 µm cryo-sections stained for PLZF (red), E-cadherin (green) and DAPI (blue) showing GSCs in interphase. Scale bars: 5 μm. C. Quantification of (B). Percentage of GSCs displaying different polarity status are indicated. CEP250+/+ n=5 mice, CEP250-/- n=4 mice. At least 100 cells were analyzed in each mouse and the average was calculated for each mouse. Data information: In white arrowheads highlight basement membrane; yellow arrowhead highlights cortical enrichment of E-cadherin towards the basement membrane. In (C data are presented as mean ± SEM. n.s., not significant, *P<0.05, **P < 0.01, ***P < 0.005 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "D. Representative images of P5 mouse ST. 10 µm cryo-sections stained for PLZF (red), E-cadherin (green) and PH3 (magenta) showing GSCs in prophase. PH3 staining marks the mitotic chromatin. Scale bars: 5 μm. E. Quantification of (D). Percentage of GSCs displaying different polarity status are indicated. CEP250+/+ n=5 mice, CEP250-/- n=4 mice. At least 10 cells were analyzed in each mouse and the average was calculated for each mouse. Data information: In white arrowheads highlight basement membrane; yellow arrowhead highlights cortical enrichment of E-cadherin towards the basement membrane. In data are presented as mean ± SEM. n.s., not significant, *P<0.05, **P < 0.01, ***P < 0.005 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "F. Representative images of P5 mouse ST 10 µm cryo-sections stained for PLZF (red), E-cadherin (green) and PH3 (magenta) showing GSCs in prometaphase. PH3 staining marks the mitotic chromosome condensation. Scale bars: 5 μm. G. Quantification of (F), percentage of GSCs displaying different polarity status are indicated. CEP250+/+ n=5 mice, CEP250-/- n=4 mice. At least 30 cells were analyzed in each mouse and the average was calculated for each mouse. Data information: In F, white arrowheads highlight basement membrane; yellow arrowhead highlights cortical enrichment of E-cadherin towards the basement membrane. In G), data are presented as mean ± SEM. n.s., not significant, *P<0.05, **P < 0.01, ***P < 0.005 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "B. Quantification of Centrosome distance in GSCs in prophase at P5. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 50 cells were analyzed in each mouse (color of dot indicates mouse). Dashed line indicates 4 μm as the threshold of well separated centrosomes. Data information: In (B), data are presented as mean ± SEM. ****P < 0.001 (the Mann-Whitney test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "E. Quantification of Percentage of prometaphase GSCs which preferentially position their mother centrosome close to the basement membrane in CEP250+/+ and CEP250-/- testis at P5. CEP250+/+ n=3 mice, CEP250-/- n=3 mice. At least 50 cells were analyzed in each mouse and the average was calculated for each mouse. Data information: In (E), data are presented as mean ± SEM. ****P < 0.001 (the unpaired Student's t-test).",
    "ncbi_link": "CEP250: 16328"
  },
  {
    "caption": "(A) BMDMs from WT (Pml+/+) and Pml-/- mice were pre-treated with zVAD (20 μM), Nec-1 (40 μM) or GSK872 (10 μM), as indicated, for 30 min followed by co-treatment with AT-406 (1 μM). Cell viability was evaluated by ATP release after 18 h. Data show mean ± SD of four biological replicates. (B) WT and Pml-/- BMDM were treated with TNF (100 ng/ml), zVAD (20 μM) and Nec-1 (40 μM) or GSK872 (10 μM), as indicated, for 16 h. Cell viability was determined by ATP release. Data show mean ± SD of three biological replicates. ",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(D) WT and Pml-/- immortalized MEFs were treated with TNF (100 ng/ml), zVAD (20 μM), Nec-1 (40 μM), and GSK872 (10 μM), as indicated, for 8 h. Cell viability was determined by ATP assay. Data show mean ± SD of three biological replicates. (E) WT and Pml-/- immortalized MEFs were treated with TNF (100 ng/ml),IKK inhibitor BMS-345541 (10 mM) and Nec-1, as indicated, for 6 h and then cell death was assayed. Data show mean ± SD of five biological replicates, except the Nec-1-containing experiment (n=2). ",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(A, B) Pml+/+ and Pml-/- BMDMs were treated with zVAD + AT406 (zA) (A) or TNF + zVAD (Tz) (B), as in Fig. 1, for the indicated times. Contents of RIPK1, p-RIPK1[S166], RIPK3, p-RIPK3, MLKL, and p-MLKL in cell lysates was analysed by immunoblots. Bottom panels, quantitation of p-RIPK1[S166] from three biological replicates using normalized intensity of p-RIPK1[S166] in WT cells at 4 h as 1. Data show mean ± SD.",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(A) Pml+/+ and Pml-/- BMDMs were treated with zVAD for 30 min, followed by AT-406 (zA) treatment at the indicated time-points, before preparing total cell lysates (TCL). TCL were immunoprecipitated with anti-FADD and the amounts of p-RIPK1[S166], RIPK1 and caspase-8 in the precipitates and TCL were analysed. (B) Pml+/+ and Pml-/- BMDMs were treated with zVAD + AT406 (zA) as in (A), and TCL were then harvested. TCL were immunoprecipitated with anti-caspase-8, and the contents of p-RIPK1[S166] and RIPK1 in the precipitates and TCL was analysed. ",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(A, B) WT (Pml+/+) and Pml-/- mice (n = 12 in each group) were injected with mouse TNF (1.5 μg/g body weight), and rectal body temperature (A) and survival (B) were determined at the indicated time-points. #, the temperature of only six mice was measured at the indicated time-points. Mean ± S.E.M is shown. *P < 0.05 as determined by two-way ANOVA (A), or by Log-rank (Mantel-Cox) test (B).",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(A) Pml+/+ and Pml-/- BMDMs were treated with TNF (100 ng/ml) + zVAD (20 μM) for the indicated timeframes. The contents of p-IKKα/β, IKKα/β, IκBα, p-MK2 and MK2 was analysed by immunoblotting. (B) Pml+/+and Pml-/- BMDMs were treated with TNF (100 ng/ml) + zVAD (20 μM) for the indicated times, and levels of p-RIPK1[S321], RIPK1, p-JNK, JNK, p-ERK, ERK, p-p38, and p38 at the indicated time points were then determined. ",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(C, D, E, F) WT (Pml+/+) and Pml-/- mice were treated with DMSO or Nec-1s (6 μg/g) or MK2 inhibitor PF-3644022 (75 μg/mouse) by intraperitoneal injection 15 min before and 60 min after intravenous TNF (1.5 μg/g body weight) injection. Body temperature (C, E) and survival (D, F) were monitored. Experiments C-F were conducted concurrently. Mean ± S.E.M is shown (C, E).",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(A, B) WT and Mk2-/- BMDMs were treated with TNF (100 ng/ml) + zVAD (20 μM) (A) or with zVAD (20 μM) + AT-406 (1 μM) (B), and then the contents of p-RIPK1[S321], RIPK1, p-p38, p38 was determined at the indicated time-points.",
    "ncbi_link": "Mk2: 17164"
  },
  {
    "caption": "(C) WT, Pml-/-, Mk2-/- and Pml-/-Mk2 -/- BMDMs were treated with zVAD (20 μM), AT-406 (1 μM), Nec-1 (40 μM) and GSK872 (10 μM), as indicated, for 18 h. Cell viability was determined by ATP release. Data show mean ± SD of three biological replicates. *P < 0.05 for multiple t-tests according to the Holm-Sidak method. (D) WT, Pml-/-, Mk2-/- and Pml-/-Mk2 -/- BMDMs were treated with TNF (100 ng/ml), zVAD (20 μM), Nec-1 (40 μM) and GSK872 (10 μM), as indicated, for 16 h. Cell viability was determined by ATP release. Data show mean ± SD of three biological replicates. *P < 0.05 for multiple t-tests according to the Holm-Sidak method. ",
    "ncbi_link": "Mk2: 17164
Pml: 18854"
  },
  {
    "caption": "(F) WT, Pml-/-, Mk2-/- and Pml-/-Mk2 -/- mice were injected i.v. with TNF (1.5 mg/kg), and survival was monitored for 24 h. Data represent a combination of two independent experiments (n=10). *P < 0.05 for Log-rank (Mantel-Cox) test.",
    "ncbi_link": "Mk2: 17164
Pml: 18854"
  },
  {
    "caption": "(D) WT and Pml-/- BMDMs were treated with TNF (100 ng/ml) + zVAD (20 μM) for the indicated times. p38 MAPK was immunoprecipitated, and its association with MK2 was then analysed.",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(B) Expression level of GFP-p62 in HeLa cells stably expressing GFP-p62 (S-GFP-p62) compared with the level of endogenous p62 in the parent HeLa cells.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(D) Bodies containing either endogenous p62 or transiently or stably transfected GFP-p62 all contain polyubiquitin. HeLa cells were fixed and stained with p62 and polyubiquitin (clone FK1) mAbs directly coupled with AlexaFluor555 (red) and AlexaFluor488 (green), respectively. Cells expressing GFP-p62 were only stained for polyubiquitin (red). Bars, 20 μm.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(B) S-GFP-p62 cells were transiently transfected with the indicated myc-tagged p62 constructs, fixed, and stained for the myc tag. Bars, 20 μm.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(A) Localization of bodies containing endogenous p62 or transiently expressed GFP-p62 relative to EEA1-positive early endosomes. Endogenous p62 were stained green using p62 antibodies directly labeled with AlexaFluor488, and EEA1 was stained red with EEA1 mAbs directly labeled with AlexaFluor555. Alternatively, transiently expressed GFP-p62 was expressed in HeLa cells, and EEA1 was stained red with EEA1 mAb (bottom). The boxed area is shown to the right at a higher magnification.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(B) The levels of p62 and LC3-II change with autophagic activity. HeLa or S-GFP-p62 cells were either left untreated or rapamycin (10 μg/ml) or bafilomycin A1 (Baf. A1; 10 μg/ml) was added for 18 h. Immunoblots were sequentially probed using LC3, p62, and actin antibodies.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(C and D) The amount of p62 located to cytoplasmic bodies increases upon inhibition of autophagy. HeLa cells or S-GFP-p62 HeLa cells were left untreated or bafilomycin A1 was added for 18 h, the cells were fixed, and p62 was either stained red using a p62 mAb (C) or imaged directly (D). Nuclei were visualized using the Draq5 DNA stain. The settings for imaging were identical for the treated cells and the untreated control.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(A) HeLa cells transiently transfected with GFP-LC3 alone or cotransfected with siRNA against p62, HA-p62, or HA-p62 D69A were either left in normal medium or starved for amino acids for 1 h. The cells were fixed, and p62 was stained using a p62 mAb. More than 200 randomly selected cells for each condition were scored for the cytoplasmic pattern of GFP-LC3 as either diffuse or punctuate. The frequency of GFP-LC3-positive cells with punctuate localization are indicated to the right.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(B) Endogenous p62 as well as coexpressed myc-tagged wild-type p62 or a UBA deletion mutant of p62 coimmunoprecipitated with GFP-LC3 from HeLa cell extracts. GFP or GFP-LC3 was immunoprecipitated from total cellular extracts after cotransfecting the indicated constructs. The cell cultures were either left untreated or starved for amino acids for 1 h as indicated. Copurified endogenous or ectopically expressed myc-tagged p62 constructs were detected using the p62 mAb. Bars, 20 μm.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(A) HeLa cells transiently expressing a Flag-tagged NH2-terminal fragment (amino acids 1-171) of huntingtin containing a 68-polyglutamine expansion, Flag-N-HttQ68. After 48 h, the cells were fixed, and Flag-N-HttQ68 was stained green using a Flag mAb. Endogenous p62 was stained red using the p62 pAb.",
    "ncbi_link": "Htt: 3064"
  },
  {
    "caption": "(C and D) The p62 shell surrounding GFP-N-HttQ68 was detected independently of the use of antibodies. (C) GFP-N-HttQ68 and DsRed-tagged p62 were cotransfected into HeLa cells, and images of live cells were obtained after 48 h of expression. The left panel shows one confocal plane of a representative GFP-N-HttQ68 and DsRed-p62 double-positive structure, and the right panel shows the Z-stack of planes with side views of the aggregate at the side and at the top. N, nucleus. (A-C) Nuclei were detected using Draq5. (D) GFP-N-HttQ68 and tdTomato-tagged p62 were cotransfected into HeLa cells, and images of live cells were obtained after 24 h of expression.",
    "ncbi_link": "Htt: 3064"
  },
  {
    "caption": "(B) The effect of coexpressing either a p62 antisense construct or a deletion construct of p62 lacking the UBA domain on N-HttQ68-induced cell death in HeLa and SHSY-5Y neuroblastoma cells.",
    "ncbi_link": "Htt: 3064
p62: 8878"
  },
  {
    "caption": "(E) Control or iRapKO MEFs were treated with or without 2 μM 4-Hydroxytamoxifen (4-OHT) for 4 days to induce Raptor knockout. Treated cells were deprived of serum for 2 hr, followed by insulin (100 nM) stimulation for 10 min, and samples were analysed by Western blot.",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "(F) SIN1 WT was expressed in SIN1 KO MEFs, and cells were selected by FACS. Cell lines were deprived of serum for 2 hr, followed by insulin (100 nM) stimulation for 10 min, and samples were analysed by Western blot.",
    "ncbi_link": "SIN1: 227743"
  },
  {
    "caption": "The active fragment of mTOR was incubated with Flag-RagC WT purified from HEK-293E cells. The kinase reaction was performed in the presence or absence of mTOR inhibitor Torin or Rapamycin. Samples were analysed by Western blot for pRagC S21",
    "ncbi_link": "Flag: 
RagC: 64121"
  },
  {
    "caption": " (A) The HA-RagC HeLa Flp-In T-Rex stable cell lines were created (See methods for details) and the expression of RagC WT or mutants was induced by addition of tetracycline overnight. Cells were deprived of serum for 2 hr followed by insulin (100nM) stimulation for 20 min. Lysates were analyzed by Western blot for levels of the specified proteins and the phosphorylation state of S6K1. Graphs indicate the mean ± S.E.M. of quantitative analyses of the western blots after normalization for total protein (* p<0.05, # no significant difference, two tailed Student's t test, n=3). (B) Expression of RagC WT, 3A or 3E was induced by addition of tetracycline overnight. Cells were serum starved for 2 hr followed by insulin (100nM) stimulation for 20 min. Lysates were analyzed by Western blot for the levels of the specified proteins and the phosphorylation state of S6K1. Graphs indicate the mean ± S.E.M. of quantitative analyses of the western blots after normalization for total protein (* p<0.05, # no significant difference, two tailed Student's t test, n=3) ",
    "ncbi_link": "HA: 
RagC: 64121"
  },
  {
    "caption": " (C) Expression of RagC WT and 3A was induced by addition of tetracycline overnight. Cells were serum starved for 2 hr followed by insulin (100nM) stimulation for indicated time. Left: Lysates were analyzed by Western blot for the levels of the specified proteins and the phosphorylation state of S6K1. Right: Graph shows mean ± S.E.M. of quantitative analyses of the Western blots after normalization for total protein, n=3 ",
    "ncbi_link": "RagC: "
  },
  {
    "caption": " (D) HEK-293E cells stably expressing RagC WT, 3A or 3E were deprived of total amino acids for 1hr followed by addition of amino acids for 10 min. Lysates were analyzed by Western blot for the levels of the specified proteins and the phosphorylation state of S6K1. Graphs indicate the mean ± S.E.M. of quantitative analyses of the western blots after normalization for total protein (* p<0.05, ** p<0.01, two tailed Student's t test, n=3) ",
    "ncbi_link": "RagC: "
  },
  {
    "caption": " (A) Expression of RagC WT, 3A, or 3E was induced by overnight addition of tetracycline in HeLa cells followed by cell size analysis using a particle size counter (Horizontal lines, box limits and whiskers represent the median, the 25th percentile ot the 75th percentile and the minimum to the maximum respectively. * p<0.05, # no significant difference, One-way ANOVA with Bonferroni multiple comparisons, n=4) ",
    "ncbi_link": "RagC: "
  },
  {
    "caption": " (B) Phospho-RagC positively regulates wing compartment size in Drosophila. Over-expression (OE) of dRagC WT, 3A, or 3E in wing posterior compartment using en-Gal4 driver and the posterior compartment sizes were measured in each genotype ((Horizontal lines, box limits and whiskers represent the median, the 25th percentile ot the 75th percentile and the minimum to the maximum respectively. ** p<0.01, *** p<0.001, **** p<0.0001, One-way ANOVA with Bonferroni multiple comparisons, n ≥ 63 flies per condition) ",
    "ncbi_link": "en: 
Gal4: 
RagC: 35793"
  },
  {
    "caption": " (C) Empty vector (EV), RagC WT, 3A or 3E were transiently expressed in stable RagC knockdown HEK-293E cells followed by cell size analysis using a particle size counter (Horizontal lines, box limits and whiskers represent the median, the 25th percentile ot the 75th percentile and the minimum to the maximum respectively. * p<0.05, ** p<0.01, **** p<0.0001, # no significant difference, One-way ANOVA with Bonferroni multiple comparisons, n=2 for C2 and n=4 for other conditions) ",
    "ncbi_link": "RagC: "
  },
  {
    "caption": " (D) Empty vector (EV), HA-RagC WT, 3A or 3E were expressed in HEK-293E cells followed 48 hr later by incubation with DMEM in the presence or absence of serum for 4 hr. Lysates were analyzed by Western blot for phosphorylation of ULK1 and total ULK1",
    "ncbi_link": "HA: 
RagC: "
  },
  {
    "caption": " (E) Empty vector (EV), HA-RagC WT, 3A or 3E were expressed in HEK-293E cells followed 48 hr later by incubation with DMEM in the presence or absence of serum for 4 hr. Chloroquine (100μM) was added to media 30 min prior to harvest. Lysates were analyzed by Western blot for levels of LC3-II and 14-3-3.Graphs show mean ± S.E.M. of quantitative analyses of LC3-II blotting after normalization for 14-3-3. * p<0.05, two tailed Student's t test, n=4 ",
    "ncbi_link": "HA: 
RagC: "
  },
  {
    "caption": " (F) GFP-LC3 was co-expressed with empty vector, RagC WT, 3A or 3E in HEK-293E cells followed 48 hr later by serum deprivation for 4 hr. Chloroquine (100μM) was added to media 30 min prior to harvest. LC3 and RagC were monitored by confocal fluorescence microscopy. Scale bar, 10 µm ",
    "ncbi_link": "GFP: 
RagC: 
LC3: 440738///81631///84557"
  },
  {
    "caption": " (A) Empty vector (EV), HA-RagC WT, 3A or 3E were transiently expressed in HEK-293E cells. RagC and lysosome maker, Lamp1, were monitored by confocal fluorescence microscopy. Scale bar, 10 μm ",
    "ncbi_link": "HA: 
RagC: "
  },
  {
    "caption": " (B) Empty vector (EV), HA-RagC WT or 3A were transiently expressed with scramble or RagC & RagD shRNA in HEK-293E cells. mTOR and HA-RagC were monitored by confocal fluorescence microscopy. Scale bar, 10 µm ",
    "ncbi_link": "HA: 
RagC: "
  },
  {
    "caption": " (C) Empty vector (EV), Flag-RagC WT, 3A or 3E were transiently expressed with HA-RagA in HEK-293E cells. Total cell lysates and amounts of mTOR, Raptor and HA-RagA in the Flag-RagC immunoprecipitates were analyzed by Western blot. Graphs show mean ± S.E.M. of quantitative analyses of Western blots (* p<0.05, two tailed Student's t test, n ≥ 3) ",
    "ncbi_link": "Flag: 
HA: 
RagA: 
RagC: "
  },
  {
    "caption": " (D) Expression of HA-RagC WT, 3A, or 3E was induced by overnight addition of tetracycline in HeLa cells. Total cell lysates (TCL) and amount of mTOR in the Raptor immunoprecipitates were analyzed by Western blot. Graphs show mean ± S.E.M. of quantitative analyses of Western blots (*** p<0.001, Student's t test, n=3)",
    "ncbi_link": "HA: 
RagC: "
  },
  {
    "caption": " (A) Relative mRNA levels of FX in CD45+ leukocytes in the peripheral blood of E0771 (abbreviated to E) or LLC tumour-bearing mice. The mean sizes of E0771 and LLC tumours were 9.8 mm and 9.5 mm, respectively. Shown are averages (N = 8 mice/group) with SEM and one-way ANOVA ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (B) Relative mRNA levels of FX in CD45+ leukocytes in various organs such as lung (Lu), Liver (Li), spleen (Sp), bone marrow (BM) and lymph node (Lymph) derived from no tumour-bearing or E0771-bearing mice. "Tumour" stands for mRNA levels of FX in E0771 tumours. Shown are averages (N = 6: organs from no tumour-bearing mice, N = 6: organs from E0771-bearing mice) with SEM and one-way ANOVA",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (E) Quantifications of fibrinogen deposition areas in TCM-stimulating wild-type mouse lungs after injection of Vtn+ HepELs. Vtn+ cells were isolated from E0771-bearing wild-type or FX-/-mouse liver by using anti-Vtn beads (1 x 106 cells /mouse). Shown are averages (N=5/ group, 3 fields/ sample) with SEM. Welch\"s t-test ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (F) Separation of Vtn+/ CD45+ HepELs from tumour-bearing FX+/- and FX-/- mouse livers by a cell sorter (Moflo Astrios). Sorted Vtn+CD45+HepELs cells obtained from a littermate (3 animals each) were pooled, and 8 x 103 Vtn+CD45+HepELs cells were i.v. injected into a tumour-bearing mouse. Right graph shows fibrinogen depositions in the lung. Shown are averages (N = 3/ group, 9 fields/ sample) with SEM. 1-way ANOVA",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (A) Representative immunostaining of fibrinogen depositions in tumour-bearing mouse lungs received an injection of rhodamine-labelled B220+CD11c+NK1.1+HepELs derived from tumour-bearing- FX+/− or FX−/− mice (scale bar, 20 μm) ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (B) Immunohistochemical quantifications of fibrinogen depositions in tumour-bearing mouse lung after an injection of B220+CD11c+NK1.1+cells derived from tumour-bearing- FX+/− or FX−/− mouse liver. Sorted B220+CD11c+NK1.1+cells were prepared from three mice per each genotype, and were i.v. injected. Shown are averages (N = 6/group, 4 sections/mouse) with SEM and Welch"s t-test ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (B) Relative mRNA levels of FX, Vtn and TSP1 in liver B220+CD11c+NK1.1+cells stimulated with LiCM or LuCM. Shown are averages (N = 6/group) with SEM and one-way ANOVA ",
    "ncbi_link": "FX: 14058
TSP1: 21825
Vtn: 22370"
  },
  {
    "caption": " (C) Relative mRNA levels of FX in liver B220+CD11c+NK1.1+cells stimulated with various factors. Shown are averages (N = 4) with SEM and one-way ANOVA ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (B) Tumour cell homing in the lungs pre-treated with LiCM-primed B220+CD11c+NK1.1+cells from tumour-bearing WT or FX−/− mouse liver. Representative photos of homing of rhodamine-labelled tumour cells (upper, scale bar, 20 μm). Number of homing tumour cells are shown (lower). Shown are averages (N = 60 sections, 5/group, all field count/section, 12 sections/sample) with SEM and Welch"s t-test ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": " (C) Tumour cell homing in the lungs pre-treated with activated FX-overexpressed B220+CD11c+NK1.1+cells (FX-OE-HepELs) from tumour-bearing lungs. Number of homing tumour cells after an injection of lung HepELs or FX-OE-HepELs are shown. Shown here are averages (N = 24 sections, 4/group, all field count/section, 6 sections/sample) SEM and one-way ANOVA ",
    "ncbi_link": "FX: 14058"
  },
  {
    "caption": "B. Scatter plot illustrates individual  mouse TSPO-PET values derived from a whole brain volume of interest. 8-15 female  mice per group at an average age of 11.1 ± 1.6 months (Grn-/- (n = 8), Trem2-/- (n = 9), Double-/- (n = 10), WT (n= 15)). Data represent mean ± SD. For statistical analysis one-way ANOVA with Tukey post hoc test was used. Statistical significance was set at *, p < 0.05; **, p < 0.01; ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "B. Volcano plot presentation of the differently expressed transcripts in  FCRLS- and CD11b-positive  Grn-/- (n=6) in comparison to WT (n=6) microglia isolated from 6-month-old male  mice. 35 out of 65 analyzed genes are significantly changed more than 20%, with 22 genes upregulated (purple) and 13 genes downregulated (blue). Data information: For statistical analysis the unpaired, two-tailed student`s t-test was performed Statistical significance was set at **, p < 0.01; ***, p < 0.001; ****, p < 0.000; ns, not significant.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "A. Western blot  of  PGRN in whole-cell lysates of WT and  GRN-/- hiMGL. Actin was used as loading control. B. Western blot of TREM2 in whole-cell lysates of WT and GRN-/- hiMGL. Mature (mTREM) and immature  TREM2  (imTREM2) are indicated.  Actin was used as loading control.",
    "ncbi_link": "GRN: 2896"
  },
  {
    "caption": "E. ELISA-mediated quantification of sTREM2 in conditioned media of GRN-/- hiMGL upon treatment with Ab1 and Ab2 (20 μg/ml, 40 μg/ml) (n = 3, biological replicates). An isotype antibody (10 μg/ml) was used as a negative control. F.  AlphaLISA-mediated quantification of p-Syk  levels in  GRN-/- hiMGL upon treatment with Ab1 and Ab2 (5 μg/ml, 10 μg/ml) with  liposomes (1 mg/ml) for 5 min. (n = 8, biological replicates). Data represent mean ± SEM. For statistical analysis in E and F one-way ANOVA with Dunnett`s post hoc test, was used to compare untreated, Ab1, and Ab2 (20 µg/ml and 40µg/ml) conditions to the isotype treated condition.",
    "ncbi_link": "GRN: 2896"
  },
  {
    "caption": "H. Uptake assay for fluorescent  myelin. GRN-/- hiMGL phagocytose significantly more myelin  as compare to WT  hiMGL. This is reversed upon treatment with TREM2 antagonistic antibodies Ab1 and Ab2 (n=4, biological replicates).",
    "ncbi_link": "GRN: 2896"
  },
  {
    "caption": "E. Transcript levels of DAM gene transcripts significantly altered in GRN-/- hiMGL, treated with  Ab1  or Ab2 in comparison to isotype treatment from the data set in A, normalized to the mean of the WT hiMGL samples (n=4, biological replicates). Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Dunnett`s post hoc test was used to compare  Ab1 and Ab2  (20 µg/ml and 40µg/ml) conditions to the isotype treated condition, Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001, *****, p < 0.00001, and ns, not significant.",
    "ncbi_link": "GRN: 2896"
  },
  {
    "caption": "A.  Western blot of CatD in total brain lysates from 14-month-old female WT, Grn-/-, Trem2-/-, and Double-/- mice. CatD maturation variants are indicated (sc: single chain; hc: heavy chain; n=3). B., C. Quantification of CatD variants in A normalized to WT (n=3 per genotype). Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Tukey's post hoc test of  Grn-/-, Trem2-/- and Double-/- was used. Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001, and ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "D., E. Catalytic activity of CatD in  brain lysates from female 6-month-old (n=4 per genotype) (D) or 14-month-old (n=3 per genotype) (E)  Grn-/-,  Trem2-/-, Double-/- mice normalized to WT. Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Tukey's post hoc test of Grn-/-, Trem2-/- and  Double-/- was used. Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001, and ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "F. Immunohistochemical analysis of  lipofuscin (green) in coronal  brain  sections. Representative images of thalamus  are shown. Scalebars = 50 μm. G. Quantification of lipofuscin autofluorescence. Five images per mouse were taken, means were normalized to WT samples (n=3 per genotype, female). Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Tukey's post hoc test of Grn-/-, Trem2-/- and Double-/- was used. Statistical significance was set at *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001, and ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "A-D. Volcano plot presentation of lipids and metabolites  upregulated (purple) or downregulated (blue) in total brain homogenates from 6-month-old male Grn-/- (A, n=5), Trem2-/- (B, n=5), Double-/- (C, n=5)  mice  in comparison to WT (n=4), and Double-/- in comparison to Grn-/- mice (D). Counts for each sample were normalized to the mean value of WT followed by a log2 transformation (n=4-5 per genotype). Analyte values were adjusted with an FDR <10% to exclude type I errors in null hypothesis testing. Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Tukey`s post hoc test of Grn-/-, Trem2-/- and Double-/- was used. Statistical significance was set at ***, p < 0.001; ****, p < 0.0001, and ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "E-G. Abundance of BMP species and  glucosylsphingosine (GlcSph) in total brain of 6-month-old  Grn-/-, Trem2-/-, Double-/- and WT mice  (n=4-5 per genotype). H. Glucocerebrosidase (GCase) activity in whole  brain lysates from 6-month-old male Grn-/-, Trem2-/-, Double-/- and WT mice. The linear increase of fluorescence signal was measured and then normalized to WT mice (n=3-6 per genotype). Data information: Data represent mean ± SEM. For statistical analysis one-way ANOVA with Tukey`s post hoc test of Grn-/-, Trem2-/- and Double-/- was used. Statistical significance was set at ***, p < 0.001; ****, p < 0.0001, and ns, not significant.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "F. Morphological analysis of cortical microglia. Representative maximum intensity projections of confocal z-stack images showing IBA1+ microglial cells of female WT, Grn-/-, Trem2-/- and Double-/- mice (scalebar = 50 µm). Arrows point to individual microglia, which are shown as three-dimensional reconstruction, scalebar = 10 µm.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "A. Immunoassay-based quantification of  neurofilament-light chain (NfL) protein levels in CSF  of 6-month-old Grn-/- (n=4), Trem2-/-(n=4), Double-/- (n=4) and WT (n=5) male mice. B. Immunoassay-based quantification of NfL  levels in CSF of 14-month-old Grn-/-, Trem2-/-, Double-/- and WT female mice (n=3 per genotype). Data information: Data in A, B represent mean ± SEM. For statistical analysis in A-B two-way ANOVA with Dunnett`s post hoc test was used the unpaired",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "D. Transcript levels of all significantly changed genes in Double-/- vs. Grn-/- brain  mRNA of 6-month-old and 14-month-old mice  analyzed in C. Grin3b was under detection limit in the 14-month-old cohort. Transcript  expression is normalized to the mean of the WT cohort. Data in D represent mean ± SEM. in D two-tailed student`s t-test was performed.",
    "ncbi_link": "Grin3b: 170483
Grn: 14824"
  },
  {
    "caption": "F. Bar graph illustrates individual FDG-PET  values derived from a whole  brain volume of interest. Data represent mean ± SD. 8-15 female  mice  per group at an average age of 10.7 ± 1.5 months (Grn-/- n = 8, Trem2-/- n = 10, Double-/- n = 10, WT n = 15) were used. Data in F two-tailed student`s t-test was performed.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "(D) Expression levels (normalised DEseq2 counts) of selected differentially expressed genes between XGFP- and XGFP+ PGCLCs  during the differentiation time course. Genes with FDR < 0.001 were considered significantly differentially expressed. Points indicate expression  of individual biological replicates.",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(H) Alkaline phosphatase staining  for ESCs, XGFP+ PGCLCs  and XGFP- PGCLCs  grown for 7 days in 2i/LIF medium on immortalised  mouse embryonic fibroblasts. (I) Barplot indicating the absolute numbers of Alkaline Phosphatase (AP) positive colonies in each cell type after 7 days of culture in 2i/LIF medium on immortalised  mouse embryonic fibroblasts. Y-axis is in square root scale (sqrt) for better plot visualisation. Each white dot represents one technical replicate.",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(H) Immunofluorescence  images of SYCP3  (red), DAZL  (yellow) and DAPI  at agg11 of IVDi tissue maturation from XGFP- PGCLCs. IVDi = in vitro differentiation. White squares indicate the positions of the magnified section shown below. Top panel scale bar = 100 μm. Middle panel scale bar = 10 μm. Bottom panel scale bar = 50 μm. (I) Quantification of SYCP3+ cells (oocytes  in cyst and  primary follicles) in IVDi tissues at agg11. Each dot represents one IVDi tissue performed in 3 biological replicates.",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(A) Schematic representation of the m220 stromal feeders expansion culture to compare the meiotic  capacity of XGFP- and XGFP+ PGCLCs. Meiosis  is induced via addition of Retinoic Acid (RA) and Bone Morphogenetic Protein 2  (BMP2). c0 = starting day of culture, c9 = culture day 9 and last day of culture. (B) Representative images for the expression  of XGFP  (green) and SYCP3  (red) in germ cells at c5, c7 and c9 from XGFP+ and XGFP- PGCLCs. All cells with SYCP3  signal irrespective of localization  pattern or intensity were scored as SYCP3+ cells. Cells were counterstained  with DAPI  (grey). Scale bars = 10 μm. (C) Number of SYCP3+ cells per m220 culture day originating from XGFP+ and XGFP- PGCLCs. Each white dot represents a biological replicate (n = 3). P-values shown are from a two-sided Mann-Whitney U test. n.s. = not significant. (D) Percentage of XGFP+ cells among SYCP3+ cells at the indicated m220 culture day, originating from XGFP+ or XGFP- PGCLCs. Green bars show constitutive GFP expression in XGFP+ PGCLC-derived cells, while striped bars signify XGFP reactivation  in XGFP- cells. Each white dot represents a biological replicate (n = 3).",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(E) Representative images showing stages of meiotic prophase I  from culture day 9 (c9)  germ cells  from XGFP+ and XGFP- PGCLCs. c9 germ cells were spread and immunostained  for SYCP3  (red), and γH2AX  (grey). Scale bars = 10 µm. (F) Quantification of meiotic progression  in culture day (c9) expanded germ cells derived from XGFP+ and XGFP- PGCLCs. The graphs show the percentages of the meiotic  stage for SYCP3+ cells. Lepto, leptotene; Zygo, zygotene; Pachy, pachytene; Diplo, diplotene. Numbers indicate detected cells per meiotic  stage and original XGFP   status.",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(G) Representative tile scan merged images of XGFP  (green) and Xtomato  (red) in  germ cells at c7 from XGFP+ and XGFP- PGCLCs. Cells were counterstained  with DAPI  (grey). Scale Bar = 1 mm. The white squares contain a magnified image of the region depicted by the white dotted squares (Scale Bar = 1 µm). (H) Density ridge plot showing size of cellular aggregates in (G) measured using the XTomato  signal. X-Axis shows area in µm2 scaled as log2. Dashed line represents the mean. XFGP- mean = 1320 µm2, XGFP+ mean = 5514 µm2. XGFP- n = 297 aggregates, XGFP+ n = 373 aggregates. P-value from two-sample unpaired Wilcoxon-Mann-Whitney test with R defaults.",
    "ncbi_link": "XGFP: "
  },
  {
    "caption": "(C) Flag-tagged Raptor was transfected with HA-tagged ArfGAP1 or HA-tagged RFP1 in wildtype (WT) or RagA/B knockout (KO) HEK293A cells for 24 hours. Cell lysates were immunoprecipitated (IP) with anti-Flag beads. IP or WCL samples were probed for HA-tagged ArfGAP1 or HA-tagged RFP1, Flag-tagged Raptor, RagA, RagB, and Vinculin the loading control.",
    "ncbi_link": "Flag: 
HA: 
ArfGAP1: 55738
RFP1: 80135
Raptor: 57521
RagA: 10670"
  },
  {
    "caption": "(G) RagA/B KO HEK293A cells were transfected with HA-tagged ArfGAP1, HA-tagged ArfGAP2, or HA-tagged RFP1 (control) for 72 hours. Cell lysates were immunoprecipitated (IP) with anti-HA beads. IP or WCL samples were probed for HA and mTORC1 components mTOR, Raptor and mLST8. Vinculin was probed as a control.",
    "ncbi_link": "HA: 
ArfGAP1: 55738
ArfGAP2: 84364
RFP1: 80135"
  },
  {
    "caption": "(D) ArfGAP1 was stably knocked down in HEK293A cells using shRNAs against ArfGAP1 (shArfGAP1) or GFP (shGFP) control. Cells were cultured under normal condition (NC; lanes 1 and 7), or starved of amino acids for 1 hour (-AA 1h; lanes 2 and 8), followed by either maintaining in amino acid starvation media (-AA; lanes 3 and 9), or addition of 1 mM of Leu (+Leu; lanes 4 and 10), Gln (+Gln; lanes 5 and 11), or Asn (+Asn; lanes 6 and 12) for 2 hours. mTORC1 activity was analyzed similar to (B). Protein levels of ArfGAP1 were confirmed by immunoblotting. S6K1 and Actin were probed as controls.",
    "ncbi_link": "GFP: 
ArfGAP1: 55738"
  },
  {
    "caption": "(E) RagA/B KO HEK293A cells were co-transfected with HA-tagged ArfGAP1, HA-tagged ArfGAP2, or HA-tagged RFP1 (control) with Myc-tagged S6K1. Cells were starved of amino acids (-AA) for 2 hours and then 4mM of Gln or Asn were added for 2 hours. mTORC1 was analyzed similar to (B). IP or WCL samples were probed for HA, Myc, and phosphorylated S6K1 at Thr 389. Actin serve as a loading control.",
    "ncbi_link": "HA: 
ArfGAP1: 55738
ArfGAP2: 84364
RFP1: 80135"
  },
  {
    "caption": "(B) Fluorescence Lifetime Imaging Microscopy (FLIM) and Förster resonance energy transfer (FRET) analysis were performed in wildtype (WT, left) or RagA/B KO (middle) HAP1 cells expressing mCherry-tagged ArfGAP1 and endogenously GFP-tagged Raptor. Cells either had amino acids (+AA) or were starved of amino acids (-AA). At least 20 cells were analyzed in each group. Box plots shows the percentage of pixels with ≥ 30% FRET efficiency of co-transfected cells. RFP1 was expressed and analyzed as a negative control. The whiskers of the boxplot represent the minimum and maximum values, while the box covers the data between 25th and 75th percentiles with a line in the middle plotted at the median. Right- Expression level of RagA/B was confirmed Western blot analysis. Actin was used as a control.",
    "ncbi_link": "GFP: 
mCherry: 
ArfGAP1: 55738
RFP1: 80135
Raptor: 57521
RagA: 10670"
  },
  {
    "caption": "(A) Mouse embryonic fibroblast (MEF) cells were transfected with HA-tagged ArfGAP1. Immunofluorescence staining was assessed for HA-tagged ArfGAP1 (blue), mTOR (green), and LAMP2 (red, lysosomal marker). Left- A representative example of the immunofluorescence staining (scale bar, 10 μm). The top left image shows the staining of HA-tagged ArfGAP1, with a white outline highlighting the region that is positive for HA-tagged ArfGAP1. This outline was overlaid with the mTOR channel (top right) and the LAMP2 channel (bottom left). The mTOR and LAMP2 channels were then merged and processed using the Squassh segmentation algorithm (Rizk et al., 2014; bottom right). The co-localization of mTOR and LAMP2 was analyzed for the region within the outline (HA-ArfGAP1 positive) and the region outside of the outline (HA-ArfGAP1-negative), respectively. Right- In each microscopy field, the image was processed as described above, and the co-localization between mTOR and LAMP2 was quantified and normalized by LAMP2 positive puncta using the Squassh algorithm (Rizk et al., 2014). The quantification was performed for the subgroups of cells that are positively or negatively stained for HA-tagged ArfGAP1, respectively, and compared using Student's t-test. Columns represent Mean ± SEM (N = 3).",
    "ncbi_link": "HA: 
ArfGAP1: 55738"
  },
  {
    "caption": "(D) MIA Paca-2 cells stably expressing FLAG-tagged or HA-tagged TMEM192 cells were cultured under normal condition (NC) or starved of amino acids (-AA), and then stimulated with 2 mM glutamine and asparagine (+Gln/Asn) for 2 hours. HA-tagged TMEM192 was immunoprecipitated (IP) with HA beads and IP and whole cell lysates (WCL) were probed for ArfGAP1, HA, RagA, or p18 (LAMTOR1). Flag, pS6K1 (mTORC1 activity), S6K1, and Vinculin were probed for as controls.",
    "ncbi_link": "FLAG: 
HA: 
TMEM192: 201931"
  },
  {
    "caption": "(D) Top - Input of GST, GST-tagged ArfGAP1, and GST-tagged ArfGAP1 L207D/V279D that was us in the in vitro binding assays. Bottom - Flag-tagged mTOR, Flag-tagged Raptor, and Flag-tagged mLST8 were overexpressed in HEK293A cells. Cell lysates were immunoprecipitated (IP) with anti-Flag beads and incubated with either GST (control), GST-tagged ArfGAP1, or GST-ArfGAP1 L207D/V279D. IP or WCL samples were probed for Flag or GST.",
    "ncbi_link": "Flag: 
mLST8: 64223
mTOR: 2475
Raptor: 57521"
  },
  {
    "caption": "(A) TCGA cohort of pancreatic cancer patients were divided into two groups according to the median level of ARFGAP1 mRNA expression. Overall survival and disease-free survival were compared between these two groups, as shown in Kaplan-Meier curves. Median survivals (in months), log-rank P values, and hazard ratios (HR) with 95% confidence intervals are indicated.",
    "ncbi_link": "ARFGAP1: 55738"
  },
  {
    "caption": "(D) MIA Paca-2 cells stably expressing short hairpin RNAs (shRNAs) against ArfGAP1 or GFP (control) were plated and treated with mTOR inhibitor Torin 1 (250 nM) or vehicle control for 48 hours prior to cell counting. Columns represent Mean ± SEM (N = 6). Student's t-test shGFP Vehicle vs. shGFP Torin 1 (P = 2.83 E-07), shGFP Vehicle vs. shArfGAP1 Vehicle (*P = 0.025), shGFP Torin 1 vs, shArfGAP1 Torin 1 (P = 0.139), and shArfGAP1 Vehicle vs. shArfGAP1 Torin 1 (P = 1.22 E-07). "ns" stands for "not significant".",
    "ncbi_link": "GFP: 
ArfGAP1: 55738"
  },
  {
    "caption": "RT-qPCR quantifying NF-κB downstream target gene expression in ArCK and euploid control (Ctrl) cells. n=6 biological replicates; mean± SEM. IL-1b, *p= 0.029; IL-6, *p= 0.032; IL-8, **p= 0.008; unpaired t-test.",
    "ncbi_link": "IL-8: 3576
IL-1b: 3553
IL-6: 3569"
  },
  {
    "caption": "ArCK or euploid proliferating control cells were treated with either DMSO or the NF-κB inhibitor BMS-345541 (5 μM) for 48 hours before assessing NK cell-mediated cytotoxicity. The drug was washed out during the NK  cell co-culture assay. n=3 biological replicates; mean± SEM. ArCK vs  ArCK NF-κB inhibitor, p< 0.0001; KS test. (H, I) The effect of inactivating both  RELA and  RELB on  NK cell-mediated cytotoxicity  in 7-day doxorubicin (H) and nutlin3-treated (I) cells. n2 biological replicates; Doxo-c1 vs.  Doxo RELA RELB-c1, p = 0.02. Nutlin-c1 vs.  Nutlin RELA RELB-c1, p = 0.44, n.s.; KS test. ",
    "ncbi_link": "RELA: 5970
RELB: 5971"
  },
  {
    "caption": "(a) Aversive associative memory performance 3 min after training (STM) was markedly reduced in 3-d-old Atg7−/− flies (Atg7d14/Atg7d77) compared with Atg7−/+ flies (Atg7d14/CG5335d30) and wild-type flies (Atg7+/+) (n = 8-11 independent experiments, F = 25.82, one-way ANOVA with Bonferroni correction). The CG5335d30 line harbors an Atg7+ chromosome related to Atg7d14 and Atg7d77 that serves as a genetic background control.",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(b) Olfactory learning was disrupted in 3-d-old female flies homozygous for Atg8a hypomorph (Atg8a−/− or Atg8aEP362/Atg8aEP362) (n = 8-9 independent experiments, F = 22.8, one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(c) STM is severely impaired in 20-d-old Atg7−/− (Atg7d14/Atg7d77) flies and 20-d-old Atg7−/+ heterozygous (Atg7d14/CG5335d30) when compared to age-matched wild-type flies (n = 8-9 independent experiments, F = 18.02, one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "Atg7: 37141"
  },
  {
    "caption": "(d) Similarly, STM was markedly decreased in 20-d-old Atg8a−/− (Atg8aEP362/Atg8aEP362) mutant female flies compared with control flies (Atg8a+/+) without any effect by spermidine feeding (n = 8-9 independent experiments, F = 68.43, one-way ANOVA with Bonferroni correction). *P 0.05, **P 0.01, ***P 0.001; ns indicates not significant, P > 0.05. Data are presented as mean ± s.e.m. The aversive olfactory avoidance and shock reactivity of different mutant are shown in Supplementary Table 5.",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(a) Aversive associative memory performance in 3 min after training (STM) in 3-d-old female flies with pan-neuronal expression of UAS-Odc-1 (n = 7 independent experiments, F = 0.04, one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "Odc-1: 35766"
  },
  {
    "caption": "(b) Aversive associative memory performance in 3 h after training (ITM), ARM and ASM of 3-d-old appl-driven UAS-Odc-1 female flies compared with control flies (n = 7 independent experiments; F = 1.95 for ITM, F = 0.10 for ARM, F = 1.05 for ASM; one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "appl: 31002
Odc-1: 35766"
  },
  {
    "caption": "(c) Pan-neuronal expression of the UAS-Odc-1 in a wild-type background suppressed AMI in 30-d-old female flies (n = 7 independent experiments, F = 21.35, one-way-ANOVA with Bonferroni correction).",
    "ncbi_link": "Odc-1: 35766"
  },
  {
    "caption": "(d) ITM, ARM and ASM of 30-d-old female flies with pan-neuronal expression of UAS-Odc-1 compared with their genetic controls (n = 7-8 independent experiments; F = 17.49 for ITM, F = 1.58 for ARM, F = 24.61 for ASM; one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "Odc-1: 35766"
  },
  {
    "caption": "(e) Expressing Odc-1 in just the mushroom body was sufficient to protect from STM decline in 30-d-old flies (n = 9-12 independent experiments, F = 9.25, one-way ANOVA with Bonferroni correction).",
    "ncbi_link": "Odc-1: 35766"
  },
  {
    "caption": "(f) ITM, ARM and ASM of 30-d-old flies expressing mushroom body-specific Odc-1 compared with their genetic controls (n = 8-9 independent experiments; F = 11.73 for ITM, F = 0.50 for ARM, F = 16.6 for ASM; one-way ANOVA with Bonferroni correction). **P 0.01, ***P 0.001; ns indicates not significant, P > 0.05. Data are presented as mean ± s.e.m.",
    "ncbi_link": "Odc-1: 35766"
  },
  {
    "caption": "YFP-hMAD2-constructs were generated Whole cell lysates of transfected HEK-293 cells were used for GST pull-down experiments. One-way ANOVA with Dunnett's multiple posthoc comparison; ***p < 0.001, ns - not significant; error bars represent SD of 3 independent biological replicates (n = 3).",
    "ncbi_link": "YFP: 
MAD2: 4085"
  },
  {
    "caption": "HEK-293 cells stably expressing YFP-hSERT were transfected with indicated siRNAs (\"C\" - ctrl siRNA; \"M\" - MAD2 siRNA) and subjected to co-immunoprecipitation. All signals were normalized to YFP-SERT. Results were compared using unpaired two-tailed t-tests; ***p < 0.001, ****p < 0.0001, ns - not significant; calculated p-values are indicated; error bars represent SD of 7 (BubR1), 8 (β2-adaptin), 5 (p31comet) and 8 (HSP70) independent biological replicates.",
    "ncbi_link": "YFP: 
MAD2: 4085
SERT: 6532"
  },
  {
    "caption": "A Radioactive substrate uptake was conducted KM and Vmax were determined by fitting the data to the equation of a rectangular hyperbola. Representative curves are shown. Error bars represent SEM. For comparison of Vmax paired two-tailed t-test was conducted; **p < 0.01, ns - not significant; exact p-value is indicated. Data are derived from 6 independent biological replicates. Lysates were prepared from an aliquot of the cells, which were used for the uptake assay, and subjected to immunoblotting to verify MAD2 knockdown. Immunodetection of α-tubulin was used as a loading control.",
    "ncbi_link": "MAD2: 4085"
  },
  {
    "caption": "B Cell surface biotinylation using HEK-293 cells stably expressing YFP-hSERT was performed Whole cell lysates and streptavidin-conjugated fractions (i.e., surface protein) were subjected to immunoblotting.",
    "ncbi_link": "YFP: 
SERT: 6532"
  },
  {
    "caption": "C - D HEK-293 cells stably expressing YFP-hSERT were transfected with the indicated siRNAs, imaged and analyzed Representative maximum intensity projections of Z-stacks are shown. Scale bars represent 50 and 20 µm in full size images and zoomed areas, respectively. Intracellular SERT-signal was measured using ImageJ software. The dot plot in panel D shows values (presented as Log10 to account for the large variation in the signal) from individual cells (Ctrl siRNA n = 112 cells; MAD2 siRNA n = 116 cells) deriving from 3 independent biological replicates, the median and the interquartile range. The statistically significant difference was assessed by an unpaired two-tailed t-test, the p-value is indicated.",
    "ncbi_link": "YFP: 
MAD2: 4085
SERT: 6532"
  },
  {
    "caption": "E - H HEK-293 cells stably expressing YFP-hSERT were transfected with the indicated siRNA, subsequently co-transfected with plasmids encoding mCherry-Rab5 (panel E) or mCherry-Rab7A (panel G) Manders' overlap coefficients for the fraction of mCherry overlapping YFP were calculated for multiple individual images using ImageJ/JACoP. Number of analyzed images: mCh-Rab5/ctrl-siRNA = 38; mCh-Rab5/MAD2-siRNA = 33 (Panel F); mCh-Rab7A/ctrl-siRNA = 13; mCh-Rab7A/Mad2-siRNA = 14 (panel H). Statistically significant differences were assessed by unpaired two-tailed t-test, the p-values were below 0.0001. Error bars represent SD of 3 independent biological replicates (n = 3). Scale bars represent 50 and 20 µm in full size images and zoomed areas, respectively.",
    "ncbi_link": "mCh: 
YFP: 
MAD2: 4085
Mad2: 4085
Rab5: 5869
Rab7A: 7879
SERT: 6532"
  },
  {
    "caption": "E Primary rat dorsal raphe neurons were cultured After 14 days, cells were infected with lentiviral particles encoding either scramble-shRNA or shRNA directed against MAD2. Five days after infection, cells were fixed in acetone/methanol (1:1) and subjected to immunofluorescence with the indicated primary and secondary antibodies. Confocal images were captured on a Nikon A1 laser scanning confocal microscope at either 20× (Fig. 5 E, left panel) or 60× (Fig. 5 E, right panel) magnification, representative images are shown. Due to imaging conditions the optical section thickness is increased at 20× compared to 60× magnification. Calibration bars in images showing rMAD2 represent arbitrary fluorescence units. Scale bars represent 50 and 10 µm for 20× and 60× magnification, respectively.",
    "ncbi_link": "MAD2: 297176"
  },
  {
    "caption": "F Surface and intracellular SERT-signal from scramble- and MAD2-shRNA infected neurons (n = 40 and n = 30, respectively) was quantified within regions of interest (ROIs) using ImageJ software and the resulting ratios compared using an unpaired two-tailed t-test, the p-value was below 0.0001 (n = 4 biological replicates). Error bars represent SD. The right part provides 4 additional representative images of both: scramble-shRNA and MAD2-shRNA expressing serotonergic neurons (SERT: orange, nuclei: blue). Scale bars represent 30 µm.",
    "ncbi_link": "MAD2: 297176"
  },
  {
    "caption": "(G) The response of mitochondrial matrix-localized (left panel) and cytosolic (right panel) roGFP2-Tsa2ΔCR probes expressed in BY4742 wild-type and Δtsa1Δtsa2 cells, to the addition of exogenous H2O2 at the indicated concentrations. Cells were grown to exponential phase in SGal (-Leu) medium. The lighter colored curves are controls, showing the probe response upon the addition of water.",
    "ncbi_link": "tsa1: 854980
tsa2: 852064"
  },
  {
    "caption": "(H) The response of mitochondrial matrix-localized (left panel) and cytosolic (right panel) roGFP2-Tsa2ΔCR probes, expressed in wild-type and Δtsa1Δtsa2 cells, to the addition of 10 µM antimycin A. Cells were grown to exponential phase in SGal (-Leu) medium. The lighter colored curves are controls showing the probe responses upon addition of 0.1% (v/v) ethanol.",
    "ncbi_link": "tsa1: 854980
tsa2: 852064"
  },
  {
    "caption": "(I) The response of a mitochondrial matrix-localized roGFP2-Tsa2ΔCR probe, expressed in wild-type and Δpor1 cells, to boli at exogenous H2O2 at the indicated concentrations. Cells were grown to exponential phase in SGal (-Leu) medium. Lighter colored curves are controls showing the probe response upon the addition of water.",
    "ncbi_link": "por1: 855669"
  },
  {
    "caption": "(J) The response of a mitochondrial matrix-localized roGFP2-Tsa2ΔCR probe, expressed in wild-type and Δpor1 cells to the addition of 10 µM antimycin A. Cells were grown to exponential phase in SGal (-Leu) medium. Lighter colored curves are controls showing the probe response upon the addition of 0.1% (v/v) ethanol.",
    "ncbi_link": "por1: 855669"
  },
  {
    "caption": "(A) The response of a mitochondrial matrix-localized roGFP2-Tsa2ΔCR probe, expressed in wild-type and Δprx1, to the addition of exogenous H2O2 at the indicated concentrations. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase. Lighter colored curves are controls showing the probe response to the addition of water.",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(B,C) The response of a cytosolic roGFP2-Tsa2ΔCR probe, expressed in wild-type, Δtrx3 and Δprx1 cells, to the addition of 0.1 mM (B) or 1 mM (C) exogenous H2O2. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase.",
    "ncbi_link": "prx1: 852215
trx3: 850444"
  },
  {
    "caption": "(D) The response of a cytosolic roGFP2-Tsa2ΔCR probe, in Δtrx3 cells transformed with a Trx3 plasmid and Δprx1 cells transformed with a Prx1 plasmid, to the addition of 0.1 mM exogenous H2O2. Cells were grown in SGal medium lacking the appropriate amino acids for plasmid selection and harvested at early exponential phase. The light grey curve in both panels represents the wild-type control, treated with the same concentration of exogenous H2O2.",
    "ncbi_link": "prx1: 852215
Prx1: 852215
trx3: 850444
Trx3: 850444"
  },
  {
    "caption": "(E) The profile of mRNA expression of the yeast redox or redox-related enzymes in Δprx1+empty vector cells, compared to Δprx1+Prx1-WT cells, both grown to an early exponential phase in SGal (-Ura) medium (n = 3 biological replicates, with cells obtained from 3 independent cultures).",
    "ncbi_link": "prx1: 852215
Prx1: 852215"
  },
  {
    "caption": "(F) The response of a cytosolic roGFP2-Tsa2ΔCR probe, in Δprx1 cells or Δctt1Δprx1 cells transformed with either an empty plasmid or a Prx1-WT plasmid to the addition of 0.1 mM exogenous H2O2. Cells were grown in SGal medium lacking the appropriate amino acids for selection and harvested in early exponential phase",
    "ncbi_link": "ctt1: 852979
prx1: 852215
Prx1: 852215"
  },
  {
    "caption": "(A) The response of a mitochondrial matrix-localized Grx1-roGFP2 sensor expressed in wild-type, Δtsa1Δtsa2, Δpor1, Δtrr2, Δtrx3 or Δprx1 cells to a bolus of exogenous H2O2 at the indicated concentrations. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase.",
    "ncbi_link": "por1: 855669
prx1: 852215
trr2: 856506
trx3: 850444
tsa1: 854980
tsa2: 852064"
  },
  {
    "caption": "(B) Left panel: The response of a mitochondrial matrix-localized Grx1-roGFP2 sensor expressed in wild-type, Δtrr2, Δtrx3 or Δprx1 cells to a bolus of 2.5 mM H2O2. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase. Right panel: Scheme depicting Prx1 and its peroxidatic cysteine at position 91.",
    "ncbi_link": "prx1: 852215
trr2: 856506
trx3: 850444"
  },
  {
    "caption": "(C) The response of a mitochondrial matrix-localized roGFP2-Tsa2ΔCR probe to exogenous 2.5 mM H2O2. The probe was expressed in wild-type cells transformed with an empty vector or in ∆prx1 cells transformed with either an empty vector, a vector encoding wild-type Prx1 or a vector encoding Prx1-C91A, grown in SGal (-Leu, -Ura). (D) The response to of a mitochondrial matrix-localized Grx1-roGFP2 sensor expressed in either wild-type cells transformed with an empty vector or in ∆prx1 cells transformed with either an empty vector, a Prx1-WT or a Prx1-C91A plasmid to exogenous H2O2 at a concentration of 2.5 mM. Cells were grown to SGal (-Leu, -Ura) medium and harvested at early exponential phase.",
    "ncbi_link": "prx1: 852215
Prx1: 852215"
  },
  {
    "caption": "(B) 'Acute stress-washout' assay. Δprx1 cells containing a Prx1-WT plasmid and expressing a mitochondrial matrix-localized Grx1-roGFP2 probe were grown to exponential phase in SGal (-Leu, -Ura) medium harvested and treated with either 0, 1, 5, 10, 25 or 50 mM H2O2 for 10 mins. After removal of H2O2 and resuspension in fresh buffer the response of a mitochondrial matrix-localized Grx1-roGFP2 probe to the addition of 1 mM H2O2 was measured. The middle panel is an enlargement of the left panel. The graph in the right panel shows the steady state Grx1-roGFP2 oxidation following H2O2 pre-treatment as well as the maximum Grx1-roGFP2 oxidation in response to the subsequent second H2O2 treatment.",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "'Acute stress-washout' assay. Δprx1 cells expressing a mitochondrial matrix-localized Grx1-roGFP2 probe were grown to exponential phase in SGal (-Leu, -Ura) medium harvested and treated with either 0, 1, 5, 10, 25 or 50 mM H2O2 for 10 mins. (C) The same experiment as in (B) performed with Δprx1 cells transformed with a Prx1-C91A plasmid.",
    "ncbi_link": "prx1: 852215
Prx1: 852215"
  },
  {
    "caption": "(D) ∆prx1 cells transformed with a vector encoding wild-type Prx1, a vector encoding the matrix-targeted D-aminooxidase (su9-DAO) and expressing a mitochondrial matrix-localized Grx1-roGFP2 were grown to exponential phase in SGal (-Leu, -Ura, -His) and then pre-treated with 0.15 M D-alanine for 0, 0.5, 1.5 hours. Afterwards, the cells were washed and the response of Grx1-roGFP2 to the addition of 1 mM H2O2 was measured.",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(E) Left panel: the response of mitochondrial matrix-localized roGFP2-Prx1 and roGFP2 probes expressed in wild-type cells to exogenous H2O2 at the indicated concentrations. Cells were grown in SGal (-Leu) medium and harvested at early exponential phase. Right panel: model illustrating that hyperoxidation of the Prx1 moiety in the roGFP2-Prx1 sensor leads to a roGFP2-like behavior.",
    "ncbi_link": "Prx1: 852215"
  },
  {
    "caption": "(H) Redox shift assays of Prx1. Δprx1 cells transformed with a plasmid encoding wild-type Prx1 were grown to early exponential phase in SGal (-Ura) medium. Cells were subsequently treated with the indicated concentrations of H2O2 for 10 mins. Exposure to H2O2 oxidizes the single cysteine of Prx1 to a state that cannot be reduced with TCEP.",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(C) Maleimide-based gel-shift assay to assess Prx1 cysteine redox state. Wild-type cells transformed with an empty plasmid or ∆prx1 cells with either an empty plasmid or a plasmid encoding wild-type Prx1, the hyperoxidation-resistant Prx1-P233stop or the inactive Prx1-C91A variants, were grown to exponential phase in SGal (-Ura) medium. Cells were subsequently treated with the indicated concentrations of H2O2 for 10 mins and then directly treated with the alkylating agent mmPEG24.",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(D) The response of a mitochondrial matrix-localized Grx1-roGFP2 probe, expressed in Δprx1 cells containing a plasmid encoding either wild-type Prx1, Prx1-P233stop or Prx1C91A to the addition of 1 mM exogenous H2O2. Cells had been pre-treated with either 10 mM H2O2 or with water as a control. For these experiments, cells were grown in SGal (-Leu, -Ura) medium and harvested at early exponential phase. OxD refers to the degree of sensor oxidation. Error bars represent the standard deviation (n = 3 biological replicates, with cells obtained from 3 independent cultures for every strain and probe combinations. For each biological replicate three technical replicates were performed).",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(E) Hydrogen peroxide 'acute stress' assay. Δprx1 cells co-transformed with empty vector or with a vector encoding either wild-type Prx1, the P233stop or the C91A variants were grown in SD (-Ura) and treated with the indicated concentrations of H2O2 for 30 mins. Afterwards, the cells were diluted and a fixed volume plated on YPD plates. The number of viable colonies was counted after 2 days growth at 30°C, here represented as a percentage relative to the 0 mM treatment. Error bars represent standard deviation (n = 5-8 biological replicates, with cells taken from independent cultures for each individual biological replicate).",
    "ncbi_link": "prx1: 852215"
  },
  {
    "caption": "(A) Hydrogen peroxide 'acute stress' assay. Δprx1 cells co-transformed with an empty plasmid or a plasmid encoding Prx1, Tsa1, PRDX3, PRDX5, PRDX6, PfAOP or PfAOP-L109M were grown in SD medium lacking the appropriate amino acids for plasmid selection and pre-treated with 0, 1, 5, 10, 25 mM H2O2 for 30 mins. Afterwards, the cells were diluted and a fixed volume was plated on YPD plates. The number of viable colonies was counted after 2 days of growth at 30°C, here represented as a percentage relative to the 0 mM pre-treatment. Error bars represent standard deviation (n = 3-8 biological replicates, with cells taken from independent cultures for each individual biological replicate). Significance was assessed with a Student's 2-tailed, unpaired, t-test. *p < 0.05; **p < 0.01; ***p < 0.001.",
    "ncbi_link": "AOP: 
PRDX3: 10935
PRDX5: 25824
PRDX6: 9588
prx1: 852215
Prx1: 852215
Tsa1: 854980"
  },
  {
    "caption": "(A) The response of a mitochondrial matrix-localized Grx1-roGFP2 probe to 1 mM H2O2. in BY4742 wild-type cells with an empty vector, in Δglr1 cells transformed either with an empty vector or a vector encoding wild-type Glr1 or the cytosolic form of Glr1, where the MTS-encoding region was removed, or in Δglr1Δprx1 cells transformed either with an empty vector or a vector encoding the cytosolic form of Glr1. Cells were grown to exponential phase in SGal (-Leu, -Ura) medium. Error bars represent the standard deviation (n = 3 biological replicates, with cells obtained from 3 independent cultures for every strain and probe combinations. For each biological replicate three technical replicates were performed).",
    "ncbi_link": "glr1: 856014
prx1: 852215"
  },
  {
    "caption": "(B) Growth curve of wild-type, Δprx1, Δglr1 and Δglr1Δprx1 cells in SD medium complemented with all amino acids (n = 3 biological replicates). Significance for the difference in the time the cultures reach 50% of their maximal OD600 was assessed with the t-test. Error bars (as ribbon) represent the standard deviation (n = 4 biological replicates, with cells taken from independent cultures for each individual biological replicate).",
    "ncbi_link": "glr1: 856014
prx1: 852215"
  },
  {
    "caption": "(C) H2O2 'acute stress' assay. Wild-type, Δprx1, Δglr1 and Δglr1Δprx1 cells pre-grown in SGal medium complemented with all amino acids to early exponential phase. Cells were treated with H2O2 at the indicated concentrations for 30 mins. Subsequently cells were diluted, and a fixed volume plated on YPD plates. The number of viable colonies was counted after 2 days growth at 30°C, here represented as a percentage relative to the 0 mM pre-treatment. Error bars represent standard deviation (n = 3 biological replicates, with cells taken from independent cultures for each individual biological replicate). An inset with a different scale on the y-axis is presented for the 1 and 5 mM concentration to allow better interpretation.",
    "ncbi_link": "glr1: 856014
prx1: 852215"
  },
  {
    "caption": "(D) H2O2 'acute stress' assay. Δprx1Δglr1 cells co-transformed with an empty plasmid or with a plasmid encoding either wild-type Prx1, the P233stop or the C91A variants were grown in SGal (-Ura) medium to early exponential phase. Cells were treated with the indicated amounts of H2O2 for 30 mins. Subsequently, the cells were diluted, and a fixed volume plated on YPD plates. The number of viable colonies was counted after 2 days growth at 30°C, here represented as a percentage relative to the 0 mM treatment. Error bars represent standard deviation (n = 3 biological replicates, with cells taken from independent cultures for each individual biological replicate).",
    "ncbi_link": "glr1: 856014
prx1: 852215"
  },
  {
    "caption": " G. Immunoblot validation of Upf1-TAP interactions with HA tagged Nmd4 and Ebs1. Control strains did not express Upf1-TAP",
    "ncbi_link": "Upf1: 855104"
  },
  {
    "caption": " H. Immunoblot validation of Upf1-TAP interaction with Pat1-HA, Lsm1-HA and Edc3-HA. The purification was performed with a mix of three strains, expressing Upf1-TAP or not (control) ",
    "ncbi_link": "Upf1: 855104"
  },
  {
    "caption": " B-D. Results of purifications using Upf1-FL (B), Upf1-CH (C as bait with the x-axis showing the average enrichment value (log2 scale) for Upf1-decapping and Upf1-23 components",
    "ncbi_link": "Upf1: 855104"
  },
  {
    "caption": " E. Comparison of the enrichment of Upf1, Nmd4 and Ebs1 in the purification of the Upf1 fragments. The Upf1 C-terminal region (854-971) affected the association with Nmd4 or Ebs1 (Student t-test with a one-sided alternative hypothesis). We compared the enrichment of each of Ebs1 and Nmd4 between purifications of Upf1 fragments having this region (Upf1-FL and Upf1-HD-Cter, 6 experiments) and purifications of Upf1 fragments lacking the extension (Upf1-CH-HD and Upf1-HD, 4 experiments). The C-terminal region had no effect on Nmd4 enrichment (p-value ≈ 0.98), whereas there was significantly less associated Ebs1 on this small region (p-value ≈ 0.0013) ",
    "ncbi_link": "Upf1: 855104"
  },
  {
    "caption": " F. Western blot of input and eluates of Upf1 domains purification in a Nmd4-HA strain. The band with the # might corresponds to a dimer of Upf1-CH, bands marked with a star correspond to residual signal with the anti-HA antibodies (Nmd4). Fragments in the eluate have a smaller size because the protein A part of the tag was removed by digestion with the TEV protease. G6PDH served as a loading control in the input samples",
    "ncbi_link": "Upf1: 855104"
  },
  {
    "caption": " A. Average enrichment of Upf1-23 and Upf1-decapping components in purified Upf1-TAP in the presence (black bars) and absence (blue bars) of NMD4. Pink and dark blue vertical lines highlight proteins of the Upf1-23 and Upf1-decapping complexes respectively. White dots correspond to individual enrichment values obtained in replicate experiments, 6 for Upf1-TAP and 3 for the nmd4Δ condition. Error bars correspond to SD ",
    "ncbi_link": "nmd4: 851077
NMD4: 851077"
  },
  {
    "caption": " B. Average enrichment of Upf1-decapping components in Nmd4-TAP in the presence (black bars) and absence (blue bars) of UPF1. White dots correspond to individual enrichment values obtained in replicate experiments, 4 for Nmd4-TAP and 2 for the upf1Δ condition. Error bars correspond to SD ",
    "ncbi_link": "UPF1: 855104
upf1: 855104"
  },
  {
    "caption": "B. Scatter plot of the mean fold change of transcripts in nmd4∆ RNAseq experiment against transcript mean fold change in ebs1∆ (Pearson correlation, r = 0.66, p-value < 2.10-16). Black dots correspond to NMD substrate examples for which individual traces are shown in Fig. EV3. Dashed lines represent boundaries of five bins of equal numbers of transcripts (2046 transcripts or notable features per bin), with bin 5 containing the transcripts that were most increased in the mutant condition compared with wild type",
    "ncbi_link": "ebs1: 851787
nmd4: 851077"
  },
  {
    "caption": "C. Percentage of transcripts affected by UPF1 deletion (increase by at least 1.4 fold) among nmd4∆ bins, as defined in B. Differences between percentages of upf1∆ affected transcripts in bin 4 and 5 and bin 3 and 4 were significant (binomial test, p<10-24). D. Same as in C, for ebs1∆. Differences between distribution of transcripts in bin n and bin n+1 were significant (binomial test, p<10-9)",
    "ncbi_link": "ebs1: 851787
UPF1: 855104
upf1: 855104
nmd4: 851077"
  },
  {
    "caption": "E. NMD efficiency of WT, upf1∆ or double mutant strains complemented with Upf1-FL, Upf1-HD-Cter or an empty plasmid. The NMD efficiency for each strain is based on reverse-transcription followed by quantitative PCR for RPL28 pre-mRNA. A wild-type strain has 100% NMD efficiency and a upf1∆ strain has 0% NMD efficiency, by definition. Each value is an average of replicate experiments, 3 for the WT condition, 5 for upf1Δ, 3 for ufp1Δ/upf2Δ, upf1Δ/ufp3Δ and upf1Δ/ebs1Δ and 4 for the upf1Δ/nmd4Δ condition. Error bars represent SD. Dots represent values obtained in the various replicate experiments",
    "ncbi_link": "ebs1: 851787
ufp1: 855104
Upf1: 855104
upf1: 855104
upf2: 856476
nmd4: 851077
RPL28: 852775
ufp3: 852963"
  },
  {
    "caption": "G. Changes in the steady-state level of the reporter encoded HA-tagged protein in upf1Δ, nmd4Δ, ebs1Δ and the nmd4Δ/ebs1Δ strains were estimated by immunoblot from three independent experiments, with one example shown",
    "ncbi_link": "ebs1: 851787
upf1: 855104
nmd4: 851077"
  },
  {
    "caption": "H. RNA decay in a wild-type and nmd4Δ/ebs1Δ strains was tested by reverse-transcription quantitative PCR specific to the 5" end of the reporter RNA at different times after transcription shut-off. The quantifications represent mean RNA amounts and standard deviation of the average (three independent experim",
    "ncbi_link": "ebs1: 851787
nmd4: 851077"
  },
  {
    "caption": " A-B. Comparison between average enrichment values for Upf1-decapping and Upf1-23 components, Lsm proteins and CK subunits in Upf1 -TAP purified samples in the presence (grey bars) or absence (blue bars) of UPF2 (AError bars represent SD. White dots represent enrichment values for individual replicates, 6 for Upf1-TAP, 3 for the upf2Δ an conditions",
    "ncbi_link": "UPF2: 856476
upf2: 856476"
  },
  {
    "caption": " A-B. Comparison between average enrichment values for Upf1-decapping and Upf1-23 components, Lsm proteins and CK subunits in Upf1-TAP purified samples in the presence (grey bars) or absence (blue bars) o UPF3 (B). Error bars represent SD. White dots represent enrichment values for individual replicates, 6 for Upf1-TAP, 3 for th upf3Δ conditions",
    "ncbi_link": "UPF3: 852963
upf3: 852963"
  },
  {
    "caption": " C-D. Evaluation of the effects of UPF2 deletion on Upf3-TAP levels (C in total extracts, in comparison with a loading control (G6PDH) was done by immunoblot",
    "ncbi_link": "UPF2: 856476"
  },
  {
    "caption": " C-D. Evaluation of the effect of UPF3 deletion on Upf2-TAP levels (D) in total extracts, in comparison with a loading control (G6PDH) was done by immunoblot",
    "ncbi_link": "UPF3: 852963"
  },
  {
    "caption": " E. Comparison between average enrichment values for Upf1-decapping and Upf1-23 components, Lsm proteins and CK subunits in Upf2-TAP purified samples in the presence (grey bars, 6 experiments) or absence (blue bars, 2 experiments) of UPF1. Error bars represent SD. The levels of expression of Upf2-TAP and Upf3-TAP proteins have been verified in this condition (Appendix Fig. S2)",
    "ncbi_link": "UPF1: 855104"
  },
  {
    "caption": " A. Unspliced RPL28, an NMD substrate, was enriched in Nmd4-TAP purification in comparison with a control untagged strain, as measured by reverse transcription followed by quantitative PCR. Bars correspond to the mean of pre-RPL28 enrichment for 3 independent experiments, as compared with RIM1, a non-NMD mRNA. Error bars correspond to SD. The indicated p-value was computed using the Welch t-test, single-sided comparison ",
    "ncbi_link": "RIM1: 
Nmd4: 851077
RPL28: 852775"
  },
  {
    "caption": " B-D. Distribution of Nmd4-TAP, Nog1 (marker of free 60S subunits) and Rps8 (marker of 40S, 80S and polysome fractions) in wild type (B), upf1∆ (C) and upf2∆ (D) strains, tested by immunoblot. Fractions 1, 2, 3 are light fractions, fractions 4, 5 and 6 correspond respectively to ribosomal 40S, 60S and 80S positions, fractions 7 to 12 correspond to polysomes. The percent of total signal for Nmd4-TAP in three independent replicates along with standard deviation of the values are indicated for each fraction",
    "ncbi_link": "upf1: 855104
upf2: 856476"
  },
  {
    "caption": " E. Quantified relative changes in Nmd4-TAP average levels in light and monosome/polysome fractions in upf1∆ and upf2∆ strains (100% correspond to levels in the wild type strain). Indicated p-values correspond to the Welch t-test, single-sided comparison of 4 replicate experiments (individual values are indicated as dots). Error bars correspond to SD ",
    "ncbi_link": "upf1: 855104
upf2: 856476"
  },
  {
    "caption": "A. Infection by a L. pneumophila strain overexpressing MvcA but not the inactive mutant MvcAC83A interferes with UBE2N modification. Raw264.7 cells were infected with the indicated bacterial strains at an MOI of 5 for 2 h. Saponin soluble proteins resolved by SDS-PAGE were probed with a UBE2N-specific antibody (top panel). The delivery of MavC and MvcA into infected cells was probed with antibodies specific to each of these two proteins. Note that MavC but not MvcA is detectable in cells infected with wild type bacteria (middle panels labeled as "translocation"). Tubulin was probed as a loading control. Protein levels of MavC and MvcA associated with the bacteria were similarly probed in the saponin insoluble fraction (lower panels labeled as "expression"). The bacterial metabolism enzyme isocitrate dehydrogenase (ICDH) was probed as a loading control. Note that endogenous MvcA was not detectable in bacteria grown in bacteriological medium (the middle panel of the lower portion).",
    "ncbi_link": "MavC: 19833713
MvcA: 19833714"
  },
  {
    "caption": "B. Coexpression of MvcA with MavC causes accumulation of unmodified UBE2N in mammalian cells. HEK293T cells were transfected with combinations of empty vector and plasmid directing the expression of MavC or MvcA. 16 h after transfection, modification of endogenous UBE2N was detected by immunoblotting (upper level). The canonical ubiquitin deamidase CifYpt from Yersinia pseudotuberculosis (Ypt), which cannot modify UBE2N, was included as a control. Note that coexpression of MvcA led to accumulation of unmodified UBE2N (4th lane) in samples that expressed MavC. The expression of MavC MvcA and Cif was detected using a Flag-specific antibody (lower panel). Tubulin was probed as a loading control (lower panel).",
    "ncbi_link": "MavC: 19833713
MvcA: 19833714"
  },
  {
    "caption": "A. Overexpression of MavC but not the inactive mutant MavCC74A in the ∆mavC∆mvcA mutant background causes IκBα accumulation in infected cells. U937 cells infected with the indicated bacterial strains at an MOI of 5 were probed for IκBα. Tubulin was probed as a loading control.",
    "ncbi_link": "mavC: 19833713
MavC: 19833713
mvcA: 19833714"
  },
  {
    "caption": "B. Prolonged UBE2N modification by MavC restricts bacterial vacuole maturation. HEK293 cells transfected to express the FcγII receptor and 4xFlag-MavC or the C74A mutant were challenged at an MOI of 1 with opsonized L. pneumophila that expresses GFP for 12 h. The vacuole was scored and categorized by the number of bacteria it contained. Data (mean +/- SE) shown were from three independent experiments, each with at least 300 vacuoles counted. *, p<0.05; **, p<0.01; n.s., not significant.",
    "ncbi_link": "FcγII receptor: 
Flag: 
GFP: 
MavC: 19833713"
  },
  {
    "caption": "C. Overexpression of MavC but not MavCC74A affects intracellular growth of the ∆mavC∆mvcA mutant of L. pneumophila. Raw264.7 cells were infected with the indicated bacterial strains and intracellular bacteria were determined at the indicated time points. Each strain was examined in triplicate and the values shown were mean +/- SE. Similar results were obtained in two independent experiments. *, p<0.1; **, p<0.01; ***, p<0.001(t-test by comparing p(MavC) with p(MavCC74A)).",
    "ncbi_link": "MavC: 19833713
mavC: 19833713
mvcA: 19833714"
  },
  {
    "caption": "D. MvcA is required for reversal of UBE2N modification during L. pneumophila infection. U937 cells infected with wild type or the ∆mvcA mutant were withdrawn at the indicated time points. Samples resolved by SDS-PAGE were probed for UBE2N, translocated MavC and MvcA. Tubulin was probed as a loading control. Note that in samples infected with the ∆mvcA strain, the level of UBE2N-Ub decreased at slower rates.",
    "ncbi_link": "mvcA: 19833714
MvcA: 19833714"
  },
  {
    "caption": "F. MvcA restores the nuclear translocation of p65 inhibited by MavC during L. pneumophila infection. Raw264.7 cells were infected with the indicated L. pneumophila strains for 2 h at an MOI of 1. Fixed cells were immunostained with antibodies specific for p65 and the bacterium, respectively. Host nuclei were labeled with Hoechst. Representative images of cells in each sample category were shown (upper panels); nuclear localization of p65 was determined by scoring at least 300 infected cells (lower panel). Results shown were from three independent experiments done in triplicate and the values shown were mean +/- SE; t-test.",
    "ncbi_link": "MvcA: 19833714"
  },
  {
    "caption": "G. Overexpression of MvcA but not its inactive mutant MvcAC83A promotes IκBα degradation during L. pneumophila infection. U937 cells were infected with the indicated bacterial strains at an MOI of 5. Lysates of cells infected for the indicated time were probed for IκBα. Tubulin was probed as a loading control. IκBα levels for cells infected with the strains ∆mvA(pMvcA) and ∆mvA(pMvcAC83A) at the indicated time points were evaluated by measuring the band intensity from three independent experiments (lower panel), the values shown were mean +/- SE; t-test.",
    "ncbi_link": "mvA: 19833714
MvcA: 19833714"
  },
  {
    "caption": "(f) Enrichment of acetylated proteins after SIRT1 inhibition in HeLa cells. Western blot analysis of SUMO2K11Ac after treatment of cells with the SIRT1 inhibitior NAM (10 mM) for 5h and subsequent enrichment for acetylated proteins via acetyl-lysine immunoprecipitation. As a control cells were either treated with control siRNA or siSUMO2/3. The samples were analyzed by immunoblotting with α-SUMO2/3 and α-SUMO2K11Ac antibodies. The α-SUMO2/3Ac and α-SUMO2K11Ac reactive species migrating at ~200 kDa are marked with an asterisk.",
    "ncbi_link": "SUMO2: 6613"
  },
  {
    "caption": "(c) The degradation of the PML reactive band (~ 120 kDa) was determined by immunoblotting. HeLa cells were either mock transfected or transfected with siRNA directed against SUMO1/2/3. The expression of RGS-His-tagged SUMO2WT or SUMO2K11Q was induced by DOX for 12 h. Prior to lysis, cells were treated with 1 μM As2O3 for 6 h. Western blot analysis for wild-type SUMO2 and SUMO2K11Q were blotted with α-RGS-His. Immunoblotting with α-Tubulin served as a loading control. Immunoblots for knockdown controls (SUMO1 and SUMO2/3) can be found",
    "ncbi_link": "His: 
SUMO1: 7341
SUMO2: 6613"
  },
  {
    "caption": "(c) Bar graph, comparing the identified SUMO-SUMO2 linkages of control and heat shock samples for SUMO2WT (gray) and SUMO2K11Q (purple). The relative abundance (y-axis) of the indicated SUMO-SUMO2 linkage sites (x-axis) are shown. The measured intensity for K11 in the SUMO2WT under control conditions was set to 100% and the relative abundance for the individual residues was calculated in relation to this value. One of two independent replicates is shown.",
    "ncbi_link": "SUMO2: 6613"
  },
  {
    "caption": "Representative flow cytometry data showing surface phenotypes of DCs sorted from spleens of wild type (WT) or Nlrc3-/- mice and treated with LPS (100 ng/ml) for 48 hours.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "WT and Nlrc3-/- mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized WT (n= 10) and Nlrc3-/- mice (n= 10).",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "Representative flow cytometry data showing intracellular production of IFN-γ and IL-17A by CD4+ T cells from the spinal cord and brain of WT or Nlrc3-/- mice 26 d after EAE induction after restimulation with MOG(35-55) peptide. Pooled data are presented in the right panel.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "Representative flow cytometry data showing surface phenotypes of DCs from spleens of WT or Nlrc3-/- mice 26 d after EAE induction.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "Expression of Nlrc3, Il12, Il6, Il23 and Il27 mRNA in DCs sorted from WT and Nlrc3-/- mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "ncbi_link": "Gapdh: 
Il12: 16160///16159
Il23: 83430
Il27: 246779
Il6: 16193
Nlrc3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized DC(WT) (n= 5) and DC(NLRC3-KO) mice (n= 5).",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Representative flow cytometry data showing intracellular production of IFN-γ and IL-17A by CD4+ T cells in the spinal cord and brain from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction after restimulation with MOG(35-55) peptide.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Recall response to MOG(35-55) by splenocytes isolated from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Expression of Il12, Il6, Il23 and Il27 mRNA in DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "ncbi_link": "Gapdh: 
Il12: 16159///16160
Il23: 83430
Il27: 246779
Il6: 16193
NLRC3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. CFSE proliferation assay of naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(WT) and DC(NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. cytokine secretion of naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs sorted from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DCs were sorted from spleens of WT or Nlrc3-/- mice. Purified DCs were treated with LPS (100 ng/ml) for specified time. DC lysates were probed for phosphorylated p65 (p-p65), total p65, p-AKT, AKT, p-p38, p38, p-ERK, ERK, p-JNK, JNK and GAPDH.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "DCs were sorted from spleens of WT or Nlrc3-/- mice. Purified DCs were treated for 48 hours with LPS (100 ng/ml) in the presence or absence of the p38 inhibitor SB203580 (10 μM or indicated concentrations). Concentrations of IL-12, IL-6, IL-23 and IL-27 in supernatants were detected by ELISA.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "DCs were sorted from spleens of WT or Nlrc3-/- mice. Purified DCs were treated for 48 hours with LPS (100 ng/ml) in the presence or absence of the p38 inhibitor SB203580 (10 μM or indicated concentrations). Cytokines in culture supernatants among naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs. NC: negative control.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "DCs were sorted from spleens of WT or Nlrc3-/- mice. Purified DCs were treated for 48 hours with LPS (100 ng/ml) in the presence or absence of the p38 inhibitor SB203580 (10 μM or indicated concentrations). CFSE proliferation assay (D) among naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs. NC: negative control.",
    "ncbi_link": "Nlrc3: 268857"
  },
  {
    "caption": "Activity phosphorylation of p38 were detected in DCs in the spleens from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction. Pooled data are presented in the right panel.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Mean clinical scores of EAE in immunized DC(WT) (n= 5) and DC(NLRC3-KO) mice (n= 5).",
    "ncbi_link": "p38: 26416
NLRC3: 268857"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Frequencies of CD4+ T cells that express IFN-γ and IL-17A in the spinal cord and brain from DC(WT) and DC(NLRC3-KO) mice 26 d after EAE induction after restimulation with MOG(35-55) peptide. Pooled data are presented in the right panel.",
    "ncbi_link": "p38: 26416
NLRC3: 268857"
  },
  {
    "caption": "DC(p38-KO) and DC(p38+NLRC3-KO) mice were immunized with MOG(35-55) peptide in CFA adjuvant and pertussis toxin to induce EAE. Expression of Il12, Il6 and Il23 mRNA in DCs sorted from spleens of DC(WT), DC(NLRC3-KO), DC(p38-KO) and DC(p38+NLRC3-KO) mice 26 d after EAE induction, presented relative to that of Gapdh.",
    "ncbi_link": "Gapdh: 
Il12: 16160///16159
Il23: 83430
Il6: 16193
p38: 26416
NLRC3: 268857"
  },
  {
    "caption": "DC(Ctrl) and DC(NLRC3-OE) were stimulated with LPS (100 ng/ml) for specified time. DC lysates were probed for p-p38, p38, NLRC3 and GAPDH. Densitometry quantification of band intensity were presented in the right panel.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(Ctrl) and DC(NLRC3-OE) were stimulated with LPS (100 ng/ml) for specified time. Enzyme-linked immunosorbent assay of cytokines in culture supernatants of DCs treated with LPS for 48 hours.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(Ctrl) and DC(NLRC3-OE) were stimulated with LPS (100 ng/ml) for specified time. Cytokines in culture supernatants among naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs treated with LPS for 48 hours.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "DC(Ctrl) and DC(NLRC3-OE) were stimulated with LPS (100 ng/ml) for specified time. CFSE proliferation assay (D) among naive 2D2 CD4+ T cells stimulated with MOG(35-55) plus DCs treated with LPS for 48 hours.",
    "ncbi_link": "NLRC3: 268857"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. Mean clinical scores of EAE (n= 5 mice per group ). Arrows indicate DC vaccine administration.",
    "ncbi_link": "GFP: 
NLRC3: 268857"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. Recall proliferative to MOG (35-55) in splenocytes taken from DCs-treated mice 26 days after EAE induction.",
    "ncbi_link": "GFP: 
NLRC3: 268857"
  },
  {
    "caption": "EAE was induced by immunization of naive B6 mice with MOG (35-55), and the mice were randomly divided into five groups. BMDCs transduced with either lentiviral vector encoding GFP and NLRC3 (LV-NLRC3) or only GFP (LV-Ctrl) were administered i.v. 4 times, once every 4 days, starting at day 10 after EAE induction. cytokine response (D) to MOG (35-55) in splenocytes taken from DCs-treated mice 26 days after EAE induction.",
    "ncbi_link": "GFP: 
NLRC3: 268857"
  },
  {
    "caption": "(A) Wild‐type (YW5‐1B), apg10‐1 mutant (MT91‐4‐2) and Δapg10 (TFD10‐L1) cells were incubated in SD(−N) medium containing 1 mM PMSF at 30°C. After incubation for 6 h, cells were observed under light microscopy (Nomarski images).",
    "ncbi_link": "apg10: 850684"
  },
  {
    "caption": "(B) Wild‐type (closed circles),apg10‐1 mutant (closed triangles) and Δapg10 (open circles) cells were grown to 1 OD600/ml in YPD and then transferred to SD(−N) medium. After incubation at 30°C for the times indicated, their viability was determined by phloxine B staining ( Tsukada and Ohsumi, 1993).",
    "ncbi_link": "apg10: 850684"
  },
  {
    "caption": "(C) Cell lysates from wild‐type cells with empty vector pRS316 (lane 1) or HAAPG12 (lane 2), and also apg10‐1 (lane 3) and Δapg10 cells with HAAPG12 (lane 4) were subjected to Western blotting analysis with anti‐HA antibody (16B12).",
    "ncbi_link": "pRS316: 
apg10: 850684
APG12: 852518"
  },
  {
    "caption": "(A) Two‐hybrid assay for interactions of Apg10p with Apg5p, Apg7p and Apg12p. Yeast cells (PJ69‐4A) harboring the indicated plasmids were streaked out on plates with medium lacking adenine to assay for interaction‐dependent activation of the ADE2 gene.",
    "ncbi_link": "ADE2: 854295"
  },
  {
    "caption": "(B) Total lysates from Δapg5 cells with HAAPG10 and/or MycAPG12 on 2μ plasmid were immunoprecipitated with anti‐HA (mAb 16B12) or anti‐Myc (mAb 9E10) antibody. Precipitates were analyzed by Western blotting using anti‐HA or anti‐Myc antibody. Apg12p adduct of Apg10p is indicated by ● and an unidentified complex of 67 kDa by ●●. The positions of cross‐reacting IgG heavy chain (H) and light chain (L) are indicated by arrowheads.",
    "ncbi_link": "APG10: 850684
APG12: 852518
apg5: 855954"
  },
  {
    "caption": "Effects of the deletion of APG5 or APG7 on Apg12p-Apg10p thioester formation. Coimmunoprecipitation was performed with wild‐type (KA311B), Δapg5 (YNM122) or Δapg7 (YTS12) cells harboring HAAPG10 and MycAPG12 on 2μ plasmids. The resulting precipitates were analyzed by Western blotting. The DTT‐resistant Apg12p-Apg5p conjugate is indicated by ●.",
    "ncbi_link": "APG10: 850684
APG12: 852518
APG5: 855954
apg5: 855954
APG7: 856576
apg7: 856576"
  },
  {
    "caption": "(A) Cell lysates from Δapg10 cells (TFD10‐L1) harboring HAAPG12 and each mutant form of HAAPG10 on CEN plasmids were subjected to Western blotting analysis with anti‐HA antibody (mAb 16B12).",
    "ncbi_link": "apg10: 850684
APG10: 850684
APG12: 852518"
  },
  {
    "caption": "(B) Cell extracts from the wild‐type cells (KA311B) harboring MycAPG12 and mutated HAAPG10 were subjected to immunoprecipitation and the resulting precipitates were analyzed by Western blotting with the rabbit anti‐HA antibody.",
    "ncbi_link": "APG10: 850684
APG12: 852518"
  },
  {
    "caption": "(A) Autophagic activities were measured by an ALP assay ( Noda and Ohsumi, 1998). YTS3 cells (Δapg10PHO8::pho8Δ60) harboring each mutant APG10 on CEN plasmids were grown to 1 OD600/ml in SC medium lacking tryptophan and then transferred to SD(−N) medium. Lysates from the cells after incubation for 0 and 4 h were used for assay. Error bars indicate the SD of three independent experiments.",
    "ncbi_link": "apg10: 850684
APG10: 850684
PHO8: 852092"
  },
  {
    "caption": "(B) Cell lysates from Δapg10 cells (TFD10‐L1) harboring empty vector, pRS316 (lane 1), wild‐type HAAPG10 (lane 2), HAAPG10C26S (lane 3), HAAPG10C133S (lane 4) or HAAPG10C137S (lane 5) on CEN plasmids were subjected to Western blotting analysis with anti‐API antiserum.",
    "ncbi_link": "pRS316: 
apg10: 850684
APG10: 850684"
  },
  {
    "caption": "D. Viability of primary human PMNs during a 2-hour ex vivo infection with the indicated S. aureus strains using the CytoTox-One Homogenous Membrane Integrity Assay to measure lactate dehydrogenase (LDH) release. Bars indicate Mean ± SEM, with n = 3. Statistical significance is indicated as follows: MOI of 100: **p = 0.0026 for p- vs LukABmut1 and ***p = 0.0003 for p- vs LukABmut2; MOI of 50: ****p <0.0001 for p- vs LukABmut1 and ****p <0.0001 for p- vs LukABmut2; MOI of 25: ***p = 0.0007 for p- vs LukABmut1 and ****p < 0.0001 for p- vs LukABmut2 using two-way ANOVA with Tukey's post hoc test correction for multiple comparisons.",
    "ncbi_link": "LukA: "
  },
  {
    "caption": "A. Depleting TRAPPC9, but not TRAPPC8, increased lipid droplet size in HEK293T cells. The efficiency of siRNA depletion of TRAPPC8 and TRAPPC9 in Hela cells is shown by immunoblotting in the top left panel.",
    "ncbi_link": "TRAPPC8: 22878
TRAPPC9: 83696"
  },
  {
    "caption": "A. Depleting TRAPPC9, but not TRAPPC8, increased lipid droplet size in HEK293T cells. Representative fluorescence images show the status of lipid droplets in these siRNA treated cells after oleic acid incubation. Bar =10 μm.",
    "ncbi_link": "TRAPPC8: 22878
TRAPPC9: 83696"
  },
  {
    "caption": "B. After loading with oleic acid, human skin fibroblasts containing a R475* mutation in TRAPPC9 accumulated lipid droplets of greater sizes than skin fibroblasts similarly isolated from a TRAPPC9 wildtype human individual. Bar = 10 μm.",
    "ncbi_link": "TRAPPC9: 83696"
  },
  {
    "caption": "Control siRNA depletion (siCtrl) was conducted with siRNA oligoes specific to a firefly luciferase sequence; siCOPB = depletion of γ-COP; siRab18 = depletion of Rab18. C9C10KO = HEK293T cells with TRAPPC9 and TRAPPC10 genes deleted. N= 3, Error bars = S.D.",
    "ncbi_link": "firefly luciferase: 
β-COP: 1315///9276
COPB: 9276///1315
Rab18: 22931
TRAPPC10: 7109
TRAPPC9: 83696"
  },
  {
    "caption": "A. Myc-TRAPPC9 directly interacted with FLAG-γ-COP. The presence of FLAG-γ-COP in immunoprecipitations of Myc-TRAPPC9 and Myc-TRAPPC10 from cell lysates of the indicated genetic backgrounds was investigated by immunoblotting.",
    "ncbi_link": "TRAPPC10: 7109
TRAPPC9: 83696"
  },
  {
    "caption": "E. Co-immunoprecipitation between TRAPPII and HA-Rab18 in control (siFFL) and γ-COP (si-γ-COP) siRNA depleted cells. TRAPPII was precipitated with transfected Myc-TRAPPC10 and the presence of HA-Rab18 was determined by immunoblotting.",
    "ncbi_link": "γ-COP: 26958///22820"
  },
  {
    "caption": "F. Co-immunoprecipitation between FLAG-γ-COP and TRAPPII in control (siFFL) and Rab18 (si-Rab18) siRNA depleted cells. TRAPPII was precipitated with Myc-TRAPPC10 and the presence of FLAG-γ-COP was determined by immunoblotting. The molecular weight of endogenous Rab18 overlaps with IgG light chain, and therefore, the amount of endogenous Rab18 precipitated with TRAPPII cannot be determined in this experiment.",
    "ncbi_link": "Rab18: 22931"
  },
  {
    "caption": "A. Huh-7 cells were depleted with control siRNA specific to firefly luciferase sequence (top panels) or with siRNA specific to γ-COP (bottom panels). Endogenous Rab18 (red) and LD (green) were stained and visualized. Bar = 10 μm.",
    "ncbi_link": "firefly luciferase: 
γ-COP: 26958///22820"
  },
  {
    "caption": "A Macroscopic seedling phenotype of 12-day-old b16b18CRISPR, quadriCRISPR F33#1/#6, pentaCRISPR and amiR-2572, compared to WT (Col-0).",
    "ncbi_link": "amiR-2572: 
CRISPR: "
  },
  {
    "caption": "E Macroscopic seedling phenotype of 12-day-old quadriCRISPR B64 compared to WT (Col-0) and amiR-2572. Scale bars = 1 cm. F, G Boxplots showing the quantification of primary root length (F) and LR density (G) in seedlings depicted in E. n = 12 (Col-0), 13 (quadriCRISPR B64), 11 (amiR-2572). D",
    "ncbi_link": "amiR-2572: 
CRISPR: "
  },
  {
    "caption": "C Confocal images of root tips in 5-day-old Col-0, amiR-2572 and syn-tasi-1522A#1 seedlings. LRC cells were indicated by white asterisks. The distal LRC cells were indicated by white arrows",
    "ncbi_link": "amiR-2572: 
syn-tasi-1522A: "
  },
  {
    "caption": "G Macroview stereo microscopic view of DR5:VENUS expression in root tips of 3-day-old WT, amiR-2572 and syn-tasi-1522A#1 seedlings, red arrows indicate DR5 stripes in the lateral root cap.",
    "ncbi_link": "amiR-2572: 
syn-tasi-1522A: "
  },
  {
    "caption": "C IAA export assay. Export of [3H]-IAA, assayed in parallel from tobacco mesophyll protoplasts expressing ABCB1, ABCB15-22 and ABCB17P980G against vector control. mean ± SE; n = 26 (vector control), 44 (ABCB1), 5 (ABCB15), 4 (ABCB16), 9 (ABCB17), 5 (ABCB18), 9 (ABCB22) and 8 (ABCB17P980G),transport experiments generated from independent tobacco transfections.",
    "ncbi_link": "ABCB1: 818265
ABCB15: 822463
ABCB16: 822465
ABCB17: 822467
ABCB18: 822468
ABCB22: 822471"
  },
  {
    "caption": "B Analysis of DR5::VENUS expression in the root elongation zone of 4-day-old pWOX5:XVE>>YUC1-2A-TAA1, in Control and amiR-2572 treated with β-estradiol (5 µM) for 0, 7.5 and 9h. Images are composed of several tiles generated in a single snap with automatic assembly, PI in gray. The zoomed images of the yellow squares are presented below each root showing the accumulation of the DR5::VENUS signal in the elongation zone.",
    "ncbi_link": "amiR-2572: 
XVE: 820259
TAA1: 843393
WOX5: 820297
YUC1: 829389"
  },
  {
    "caption": "A Fluorescence of YFP-ABCB17 in the root meristem and leaf in 3-day-old F1 crosses with WT, syn-tasi-1522A#1 and amiR-2572, propidium iodide (PI) in magenta. Red arrows highlight the position of the epidermis . Scale bars = 50 µm. B Schematic representation of root geometry with the indication of regions of interest for YFP-ABCB17 signal quantification. Red (Stele), and black (epidermis/LRC). C, D Quantification of YFP-ABCB17 fluorescence intensity in the stele (C) and epidermis/LRC (D) of A, measured at regions of interest corresponding t",
    "ncbi_link": "amiR-2572: 
syn-tasi-1522A: "
  },
  {
    "caption": "G,H Quantification of the oscillation period (G) and amplitude (H) of DR5::LUC in 3-day-old WT and syn-tasi-1522A#1, n= 27 (WT) and 23 (syn-tasi-1522A#1).",
    "ncbi_link": "syn-tasi-1522A: "
  },
  {
    "caption": "B. Western blot of oocyte lysate (left) and biotinylation-purified surface (right) samples showing the expression of PC1 and PC2 in Xenopus oocytes and enhanced surface trafficking of the PC1/PC2 complex compared to either protein expressed separately. Anti-PC1 C-terminus antibody [29] recognized both full-length (asterisk) and GPS-cleaved CTF (open circle) of PC1. A higher-glycosylated 130 kDa PC2 (star) band was only seen when PC1 is coexpressed.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "C. Co-IP followed by western blot showing the association between PC1 and PC2 that were expressed in Xenopus oocytes. IP was done with an anti-FLAG antibody. Bands of full-length (asterisk) and GPS-cleaved CTF (open circle) of PC1 are indicated. Both 120 and 130 kDa bands of PC2 were seen in the IPed product.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "D. Representative current-voltage relationship (I-V) curves (left) and a scatter plot and bar graph (right) showing coexpression of WT PC1 and PC2 produced no current in TEVC recording. The current of the GOF PC2_F604P is included as a control. Currents at +60 mV are shown in the bar graph. Each point represents the recorded current from one oocyte. Oocyte numbers for scatter plot and bar graph are indicated in parentheses. Data are presented as mean ± SD (***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "B. Representative I-V curves (left) and a scatter plot and bar graph (right) showing that the PC2_AA is a GOF mutant and gave rise to a larger current than PC2_F604P. Scatter plot and bar graph shows the average current sizes at +60 mV. The cations included in the bath solution, 100 mM Na+ and 2 mM Ca2+ in this case, are indicated by the thick-lined boxes here and in all the following figures. Oocyte numbers for bar graph are indicated in parentheses. Data are presented as mean ± SD in bar graph (***P < 0.001, Student's t-test).",
    "ncbi_link": "PC2: 5311"
  },
  {
    "caption": "C. Representative currents of PC2_F604P and PC2_AA mutants in the divalent ion-free bath solution, which contains 100 mM Na+.",
    "ncbi_link": "PC2: 5311"
  },
  {
    "caption": "D. Representative currents of indicated WT and mutants of PC2 in a bath solution containing 70 mM Ca2+.",
    "ncbi_link": "PC2: 5311"
  },
  {
    "caption": "E. Calcium-activated chloride channel (CaCC) blocker MONNA (10 μM) or niflumic acid (NFA) (1 mM) partially blocked the current recorded from the PC2_AA-injected oocytes in the 70 mM Ca2+ bath solution.",
    "ncbi_link": "PC2: 5311"
  },
  {
    "caption": "A, B. Representative I-V curves (left) and scatter plot and bar graphs (right) showing the currents from oocytes expressing PC2_AA alone, PC1 with PC2_AA, and PC1 with WT PC2, in bath solutions containing 100 mM Na+ (A), and 100 mM Na+ and 2 mM Ca2+ (B). Scatter plot and bar graphs show currents at +80 mV and -80 (or -70) mV. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD in bar graph (n.s.: not significant, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "C. Representative I-V curves of PC1/PC2_AA recorded in a bath solution containing 100 mM Na+ and 2 mM Ca2+ solution in the absence or presence of 10 μM MONNA.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "D. Representative I-V curves (left) and scatter plot and bar graphs (right) showing the currents from oocytes expressing PC2_AA alone, PC1 with PC2_AA, and PC1 with WT PC2, in bath solutions containing 70 mM Ca2+. Scatter plot and bar graphs show currents at +80 mV and -70 mV. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD in bar graph (***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "E. Representative I-V curves of PC1/PC2_AA recorded in a bath solution containing 70 mM Ca2+ solution in the absence or presence of 10 μM MONNA.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "F. Representative currents of PC2_AA (left) and PC1/PC2_AA (right) in solutions containing the indicated Ca2+ concentrations. All solutions contain 20 μM of MONNA to block CaCC current. Corresponding concentrations of NMDG+ were added to compensate the osmolarity. See Fig EV2 for currents of the full voltage scale and the details of solutions used.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "G. Scatter plot and bar graph showing the higher radiolabeled 45Ca uptake rate of oocytes expressing the PC1/PC2_AA complex channel compared to that of oocytes expressing PC1 alone or PC2 alone. For oocytes injected with PC2 alone, five times more concentrated PC2 RNA was injected to increase its surface expression. The purple dashed line indicates the background 45Ca uptake set by the measurement with the water-injected oocytes. Data were averaged from three independent experiments. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD in bar graph (***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves (left) and scatter plot and bar graphs (right) showing the comparison between the currents of full-length PC1/PC2_AA with that of PC1-CTF/PC2_AA in bath solutions containing 100 mM Na+ (B), Currents at both +80 mV and -80 (or -70) mV are displayed in the scatter plot and bar graphs. Oocyte numbers are indicated in parentheses.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves (left) and scatter plot and bar graphs (right) showing the comparison between the currents of full-length PC1/PC2_AA with that of PC1-CTF/PC2_AA in bath solutions containing 100 mM Na+ and 2 mM Ca2+ (C) Currents at both +80 mV and -80 (or -70) mV are displayed in the scatter plot and bar graphs. Oocyte numbers are indicated in parentheses.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves (left) and scatter plot and bar graphs (right) showing the comparison between the currents of full-length PC1/PC2_AA with that of PC1-CTF/PC2_AA in bath solutions containing 70 mM Ca2+ (D). Currents at both +80 mV and -80 (or -70) mV are displayed in the scatter plot and bar graphs. Oocyte numbers are indicated in parentheses.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "E. Scatter plot and bar graph showing that the current of PC1-CTF/PC2_AA is completely abolished when WT PC2 was used, or after introducing R4090W mutation in the putative pore region of PC1-CTF. Inserted are western blot images showing the expression of the corresponding proteins. Top: anti-PC1. Bottom: anti-PC2. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD in bar graph (***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves of oocytes injected with the indicated RNAs in a bath solution containing 100 mM Na+ and 2 mM Ca2+ (F), showing PC1-TLD/PC2_AA gave rise to current with similar properties as full-length PC1/PC2_AA channel.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves of oocytes injected with the indicated RNAs in a bath solution containing 100 mM Na+ (G), , showing PC1-TLD/PC2_AA gave rise to current with similar properties as full-length PC1/PC2_AA channel.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative I-V curves of oocytes injected with the indicated RNAs in a bath solution containing 70 mM Ca2+ (H), showing PC1-TLD/PC2_AA gave rise to current with similar properties as full-length PC1/PC2_AA channel.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "I. Co-IP followed by western blot showing the association between PC2_AA and the indicated full-length or fragments of PC1. Bands of full-length (asterisk), GPS-cleaved CTF or expressed CTF fragment (open circle), and TLD (star) of PC1 are indicated.",
    "ncbi_link": "PC1: 18763"
  },
  {
    "caption": "J. Surface biotinylation followed by western blot showing the expression of the complexes formed between PC2_AA and full-length PC1, PC1-CTF, or PC1-TLD at the oocyte surface. Besides the blots shown in the figure, surface samples were also blotted with an anti-PC1 N-terminus antibody, and the cleaved NTF fragment was found associated to the plasma membrane in the full-length sample (shown in Appendix Fig S4). Bands of full-length (asterisk), GPS-cleaved CTF or expressed CTF fragment (open circle), and TLD (star) of PC1 are indicated.",
    "ncbi_link": "PC1: 18763"
  },
  {
    "caption": "A. Representative I-V curves of the PC2_AA and PC1-CTF/PC2_AA channels in divalent ion-free bath solutions containing 100 mM of indicated ions, showing the differences in reversal potential.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "B. Bar graphs showing the markedly different reversal potentials of PC2_AA channel and the PC1-CTF/PC2_AA channel in bath solutions containing 100 mM of the indicated ions. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD (n.s.: not significant, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Bar graphs showing the reversal potentials of PC1-CTF/PC2_AA and the indicated mutants tested in bath solutions containing 100 mM of the indicated ions. Two PC1 and two PC2 mutations caused dramatic changes in the reversal potential for almost all tested ions (B), indicating that these amino acids are essential for ion permeability. Statistical significance between reversal potentials of all pore mutants and that of the PC1-CTF/PC2_AA channel are indicated. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD (n.s.: not significant, **P < 0.01, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Bar graphs showing the reversal potentials of PC1-CTF/PC2_AA and the indicated mutants tested in bath solutions containing 100 mM of the indicated ions. Another two PC1 mutations and one PC2 mutation only led to relatively small changes of reversal potential for some ions but not others (C), indicating a less important role of these amino acids in ion permeability. Statistical significance between reversal potentials of all pore mutants and that of the PC1-CTF/PC2_AA channel are indicated. Oocyte numbers are indicated in parentheses. Data are presented as mean ± SD (n.s.: not significant, **P < 0.01, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Bar graphs showing the permeability ratios of the indicated ions to that of Na+ (Px: PNa) (D) Pore mutations in both PC1 and PC2 lead to significant changes in the permeability ratios in most of the cases.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Bar graphs showing the permeability ratios of the indicated ions to that of NMDG+ (Px: PNMDG) (E). Pore mutations in both PC1 and PC2 lead to significant changes in the permeability ratios in most of the cases.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative currents and a scatter plot and bar graph showing the currents of the full-length WT and mutant PC1s associated with PC2_AA in bath solutions containing 100 mM Na+ and 2 mM Ca2+ (B) Currents were normalized to the average current of PC1/PC2_AA recorded from the same batch of oocytes. Oocyte numbers in scatter plot and bar graph are indicated in parentheses. Data are presented as mean ± SD in bar graph (n.s.: not significant, **P < 0.01, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "Representative currents and a scatter plot and bar graph showing the currents of the full-length WT and mutant PC1s associated with PC2_AA in bath solutions containing 100 mM Na+ and 70 mM Ca2+ (C). Currents were normalized to the average current of PC1/PC2_AA recorded from the same batch of oocytes. Oocyte numbers in scatter plot and bar graph are indicated in parentheses. Data are presented as mean ± SD in bar graph (n.s.: not significant, **P < 0.01, ***P < 0.001, Student's t-test).",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "D. Surface biotinylation followed by western blot showing the surface expression of the PC1_T3041V/PC2_AA complex, but not the PC1_L3040H/PC2_AA complex, in Xenopus oocytes. PC2_AA is completely absent from the surface sample when PC1_L3040H was coexpressed, indicating that, in our experimental condition, almost all PC2_AA were in the complex with PC1_L3040H and trapped in the process of cell surface trafficking. Bands of full-length (asterisk) and GPS-cleaved CTF (open circle) of PC1, and 130 kDa PC2 (star) are indicated.",
    "ncbi_link": "PC1: 18763
PC2: 5311"
  },
  {
    "caption": "qRT-PCR analysis of Foxp1-4 in murine ECs freshly isolated from P11 mesentery (n = 6 mice, individual data points shown). Data are presented as mean relative expression (normalized to Gapdh) ± SD. Transcript levels for each transcript are presented relative to levels in LECs. P, Student's t-test. nd, not detected.",
    "ncbi_link": "Foxp1: 108655"
  },
  {
    "caption": "Whole-mount immunofluorescence of P7 mesenteries, showing efficient FOXP2 depletion in Foxp2flox/-;Tie2-Cre vessels. Dotted line indicates vessel width. Quantification of mesenteric collecting lymphatic vessel width in P7 Foxp2flox/-;Tie2-Cre and littermate controls (n = vessels [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
Foxp2: 114142
Tie2: 21687"
  },
  {
    "caption": "Lymphatic valves in P7 mesenteric vessels of control and Foxp2flox/-;Tie2-Cre mice. A spectrum of defects in the mutants ranging from shortened integrin-α9+FN-EIIIA+ valve leaflets (middle panels) to a complete loss of leaflets (right panels) are shown. Quantification of the proportion of valves with integrin-α9+ leaflets (G), and leaflet length (H) in P7 Foxp2flox/-;Tie2-Cre and littermate controls (n = valves [mice], as indicated). Leaflet length = 0 corresponds to valves with no leaflets.",
    "ncbi_link": "Cre: 2777477
FN-EIIIA: 319448
Foxp2: 114142
integrin-α9: 104099
Tie2: 21687"
  },
  {
    "caption": "Whole-mount immunofluorescence (A) and quantification of NRP2 staining intensity (B) in P6 mesenteric lymphatic vessels of Foxp2flox/-;Tie2-Cre and littermate control mice (n = vessels [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
Foxp2: 114142
Tie2: 21687"
  },
  {
    "caption": "RNAscope-based whole-mount in situ hybridization (C) and quantification of Efnb2 transcript levels (D) in P7 mesenteric lymphatic vessels of Foxp2flox/-;Tie2-Cre and littermate control mice (n = vessels [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
Efnb2: 13642
Foxp2: 114142
Tie2: 21687"
  },
  {
    "caption": "Whole-mount immunofluorescence of P6 mesenteries, showing valve defects in the mutant vessels. Quantification of lymphatic valve numbers (C), valve leaflet length (D) and vessel width (E) in Foxp2flox/flox;Prox1-CreERT2 and littermate control mice (n = vessels (C, E) or valves (D) [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
ER: 2099
Foxp2: 114142"
  },
  {
    "caption": "qRT-PCR analysis of FOXP2, FOXC2 and GJA4 expression in control (siCTRL) and FOXP2 or FOXC2 siRNA-treated HDLECs (n = 6 (FOXP2, FOXC2) or n = 3 (GJA4) independent experiments).",
    "ncbi_link": "FOXC2: 2303
FOXP2: 93986
GJA4: 2701"
  },
  {
    "caption": "Top panels: whole-mount immunofluorescence of E18 Foxc2flox/flox;Prox1-CreERT2 and littermate control mesenteries, showing downregulation of FOXP2 in Foxc2 deficient vessels. Bottom panels: extraction of nuclear FOXP2 staining (grey) using IMARIS surface mask generated based on PROX1 staining (green). Unmasked FOXP2 staining is shown in magenta. Quantification of FOXP2 levels in mesenteric lymphatic vessels of Foxc2flox/flox;Prox1-CreERT2 and control littermates based on nuclear FOXP2 signals as in (B) (n = vessels [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
ER: 2099
Foxc2: 14234
Prox1: 19130"
  },
  {
    "caption": "Whole-mount immunofluorescence of P8 mesenteric lymphatic vessels of Foxp2flox/-;Tie2-Cre and littermate control mice showing loss of organized FOXC2high valve regions but unaltered expression of FOXC2 in Foxp2 deficient vessels. Whole-mount immunofluorescence of lymphatic valves in P7 mesenteries of control and Foxp2flox/-;Tie2-Cre mice showing NFATc1 subcellular localization. Note predominantly nuclear localization of NFATc1 in control valves (left panels), but cytoplasmic localization (middle panels, 3 out of 5 mice) or downregulation of NFATc1 (right panels, 2 out of 5 mice) in the mutant valves. Quantification of protein localization in NFATc1+ lymphatic valves from (D) (n = valves [mice], as indicated).",
    "ncbi_link": "Cre: 2777477
Foxp2: 114142
Tie2: 21687"
  },
  {
    "caption": "Demonstration of translational readthrough of AGO1 using luciferase-based reporter assay. Plasmid containing in-frame AGO1-TGA (or GCA)-ISR-FLuc were transfected in HEK293 cells and translational readthrough was detected as FLuc activity normalized to the activity of co-transfected renilla luciferase (RLuc). FLuc mRNA levels determined by RT-PCR are shown below. ***, P = 0.0001.",
    "ncbi_link": "FLuc: 
luciferase: 
RLuc: 
AGO1: 26523"
  },
  {
    "caption": "Significance of the identity of the canonical stop codon in AGO1 translational readthrough. AGO1-ISR-FLuc constructs containing TGA or TAA or TAG were transfected in HEK293 cells and translational readthrough was quantified as described above. FLuc mRNA levels determined by RT-PCR are shown below. ***, P = 0.0002; **, P = 0.0004.",
    "ncbi_link": "FLuc: 
AGO1: 26523"
  },
  {
    "caption": "First 57 nucleotides of ISR are sufficient to drive AGO1 translational readthrough. AGO1-TGA-FLuc constructs with different lengths of ISR (all in-frame with AGO1 and FLuc) were in vitro transcribed and in vitro translated using rabbit reticulocyte lysate. FLuc activity reflects readthrough activity. **, P = 0.012; *, P = 0.017.",
    "ncbi_link": "FLuc: 
AGO1: 26523"
  },
  {
    "caption": "Demonstration of translational readthrough of AGO1 using fluorescence-based reporter assay. Plasmid containing in-frame AGO1-TGA (or GCA)-ISR-GFP were transfected in HEK293 cells and translational readthrough was detected as fluorescence. Scale bar, 50 um. The bar graph shows mean fluorescence intensities in cells transfected with indicated constructs. Fluorescence intensity was measured by flowcytometry. ***, P = 0.007.",
    "ncbi_link": "GFP: 
AGO1: 26523"
  },
  {
    "caption": "Expression of Ago1x in HEK293 cells transfected with three AGO1-specific siRNAs (1,2,3). qRT-PCR analysis of AGO1 transcript expression in these cells is shown below.",
    "ncbi_link": "AGO1: 26523"
  },
  {
    "caption": "Presence of ribosome footprint in the Inter stop codon region of AGO1 transcript in U2-OS cells. Ribosome profiling data was taken from NCBI's sequence read archive (SRA Accession no. SRR1257257) and ribosome footprints on AGO1 transcript were analyzed as described in Methods section. Zoomed area near the inter-stop codon region is shown in the inset. Position of canonical stop codon and the downstream in-frame stop codon are shown. Detection of Ago1x by Western blot in U2-OS cells is shown (right).",
    "ncbi_link": "AGO1: 26523"
  },
  {
    "caption": "Effect of let-7a overexpression on translational readthrough of AGO1. HeLa cells were stably transfected with pri-let-7a overexpression construct. Ago1x expression was determined by Western blot. Densitometric analysis of three independent experiments is shown as a bar diagram (mean ± S.E.). *, P = 0.007.",
    "ncbi_link": "let-7a: 406882///406883///406881"
  },
  {
    "caption": "let-7a inhibitor reduces the AGO1 readthrough efficiency. HeLa cells were transfected with let-7a inhibitor or control inhibitor along with AGO1-TGA (or GCA)-ISR-FLuc construct. Readthrough was quantified by measuring FLuc activity, which was normalized to co-transfected renilla luciferase activity. FLuc mRNA expression in HeLa cells treated with miRNA inhibitors is shown (Right). *, P = 0.027.",
    "ncbi_link": "FLuc: 
AGO1: 26523"
  },
  {
    "caption": "AGO1 ISR with mutated let-7a binding site shows reduced translational readthrough activity. Assay was done as described above in HeLa cells. Mutated sequence is shown (top). ***, P = 0.008.",
    "ncbi_link": "AGO1: 26523"
  },
  {
    "caption": "AGO1 ISR with displaced let-7a binding site (AGO1-TGA-disISR-FLuc) shows reduced translational readthrough activity. let-7a binding site was moved 18 nucleotides downstream of the stop codon. Readthrough assay was done as described above in HeLa cells. ***, P < 0.0001.",
    "ncbi_link": "FLuc: 
AGO1: 26523"
  },
  {
    "caption": "AGO1 ISR can drive translational readthrough in a heterologous context of RHOA. AGO1 coding sequence in AGO1-TGA-ISR-FLuc construct was replaced by RHOA coding sequence (582 nucleotides) and the readthrough assay was done as described above in HeLa cells. 3′UTRRho, 159 nucleotides in the proximal 3′UTR of RHOA (NM_001664); ISRAgo1, Inter-stop codon region of AGO1. ***, P < 0.0001.",
    "ncbi_link": "FLuc: 
AGO1: 26523
Ago1: 26523
RHOA: 387
Rho: 387"
  },
  {
    "caption": "AGO1 ISR can drive translational readthrough in a heterologous context of renilla luciferase (RLuc). AGO1 coding sequence in AGO1-TGA-ISR-FLuc construct was replaced by RLuc coding sequence and the readthrough assay was done as described above in HeLa cells (left) and in vitro using rabbit reticulocyte lysate system (right). **, P = 0.006; ***, P = 0.0001.",
    "ncbi_link": "RLuc: 
FLuc: 
luciferase: 
AGO1: 26523"
  },
  {
    "caption": "Tethering of N-peptide-tagged Ago1 or Ago1x can induce readthrough of AGO1. Two BoxB elements were cloned downstream of the AGO1 and upstream of the in-frame FLuc as shown in the schematic. This construct was transfected in HeLa cells expressing N-peptide-tagged or FLAG-tagged Ago proteins as indicated. Readthrough was measured as described above. *, P = 0.035 (with Welch correction); **, P = 0.016.",
    "ncbi_link": "BoxB: 
FLuc: 
AGO1: 26523"
  },
  {
    "caption": "RT-PCR results showing PTEN and MYC mRNAs co-immunoprecipitated with Ago1 or Ago1x in HeLa cells.",
    "ncbi_link": "MYC: 4609
PTEN: 5728"
  },
  {
    "caption": "Expression of RLuc protein in HeLa cells expressing N-HA-tagged or untagged Ago proteins as indicated. Densitometric analysis of three independent experiments is shown as bar graph (mean ± S.E.). RT-PCR analysis for RLuc mRNA level is shown (bottom). **, P = 0.001.",
    "ncbi_link": "RLuc: "
  },
  {
    "caption": "Activity of RLuc relative to co-transfected FLuc in HeLa cells expressing N-HA-tagged Ago2 (N-HA-Ago2) or N-HA-tagged chimeric Ago2 appended with the ISR region of Ago1x (N-HA-Ago2-ISRAgo1) as indicated. Bar graph (mean ± S.E.) is a representative of three independent experiments done in triplicates. Expression of HA-tagged Ago proteins was confirmed by Western blot (bottom). ***, P < 0.0001; **, P = 0.0004.",
    "ncbi_link": "HA: 
Ago1: 26523
Ago1x: 26523
Ago2: 27161"
  },
  {
    "caption": "Ribopuromycylation assay showing global translation profile of HeLa cells overexpressing FLAG-HA-Ago1 or FLAG-HA-Ago1x. Densitometric analysis of four independent experiments is shown as bar graph (mean ± S.E.). Puromycin densities were normalized to ponceau S stain densities. *, P < 0.029 (Mann-Whitney test).",
    "ncbi_link": "FLAG: 
HA: 
Ago1: 26523
Ago1x: 26523"
  },
  {
    "caption": "[35S]-methionine autoradiogram showing global translation profile of HeLa cells overexpressing FLAG-HA-Ago1 or FLAG-HA-Ago1x. Densitometric analysis of three independent experiments is shown as bar graph (mean ± S.E.). Autoradiogram densities were normalized to Coomassie stain densities. *, P < 0.029 (Mann-Whitney test).",
    "ncbi_link": "FLAG: 
HA: 
Ago1: 26523
Ago1x: 26523"
  },
  {
    "caption": "(A) Blood ammonia in 8-9-week-old C57BL/6J wild-type (WT) mice (n=8) and Becn1F121A mice with constitutive activation of autophagy (n=8) at baseline and 30 min after i.p. injection of NH4Cl (10 mmol/kg). **p<0.01 (Unpaired t-test). ns: not statistically significant difference.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(A) Survival curves of AslNeo/Neo mice and age-matched wild-type (WT) controls treated with TB-1 (15 mg/kg, i.p., every 48 hours starting at day 10 of age) or vehicle. WT + Vehicle n=8; WT + TB-1 n=8; AslNeo/Neo + Vehicle n=20; AslNeo/Neo + TB-1 n=16. *p<0.05 (Log-rank Mantel-Cox test). Data information: All values are shown as averages ± S.E.M. ns: not statistically significant difference.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(B) Isotopic enrichment of 15N-labeled urea in blood, 20 min after i.p. injection of 15NH4Cl tracer (4 mmol/kg) in AslNeo/Neo mice treated with TB-1 (n=15) or vehicle (n=9). *p<0.05 (Unpaired t-test). Data information: All values are shown as averages ± S.E.M. ns: not statistically significant difference.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(C) Representative Western blotting bands of LC3, p62 and NBR1 in livers of AslNeo/Neo mice treated with TB-1 or vehicle. GAPDH and β-actin were used as loading controls. (D) Densitometric quantifications. AslNeo/Neo + Vehicle n=5; AslNeo/Neo + TB-1 n=9. **p<0.01, *p<0.05 (Unpaired t-test). Data information: All values are shown as averages ± S.E.M. ns: not statistically significant difference.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(E) Argininosuccinate in dried blood spots (DBS) of WT and AslNeo/Neo mice injected with TB-1 or vehicle (n=4-14 mice/group). ***p<0.001, *p<0.05 (One-way ANOVA). Data information: All values are shown as averages ± S.E.M. ns: not statistically significant difference.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(F) Isotopic enrichment of 15N-labeled argininosuccinate in livers of AslNeo/Neo mice treated with TB-1 (n=11) or vehicle (n=5). *p<0.05 (Unpaired t-test). Data information: All values are shown as averages ± S.E.M. ns: not statistically significant difference.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(A) Hematoxylin and eosin (H&E, upper panels) and periodic acid Schiff (PAS, lower panels) staining of liver samples harvested from wild-type (WT) and AslNeo/Neo mice treated with TB-1 or vehicle. Scale bars: 500 µm.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(C) Quantification of hepatic glycogen in vehicle (n=6)- and TB-1-treated AslNeo/Neo mice (n=12) compared to WT (n=5) controls. **p<0.01, *p<0.05 (One-way ANOVA). Data information: All values are shown as averages ± S.E.M.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(D) Representative Western blotting bands and densitometric quantification of PYGL in livers of WT and AslNeo/Neo mice treated with either with TB-1 or vehicle (n=4 mice/group). *p<0.05 (One-way ANOVA). GAPDH was used as loading control. Data information: All values are shown as averages ± S.E.M.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(E) Representative electron microscopy images of liver samples harvested from WT and AslNeo/Neo mice treated with TB-1 or vehicle. Scale bar: 900 nm.",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "(A) Representative electron microscopy images of liver samples harvested from wild-type (WT) and AslNeo/Neo mice treated with TB-1 or vehicle. False color on the images indicates glycogen within the nuclei. Scale bar: 1 μm. (B) Quantification of nuclei containing glycogen (approx. 180 nuclei were analyzed in total per condition, n=3 mice/group). ",
    "ncbi_link": "Asl: 109900"
  },
  {
    "caption": "Representative still images of control, Rod depleted cells and Rod depleted cells supplemented with RNAi resistant Venus-Rod treated with nocodazole and time in minutes indicated. Scale bar, 5 μm.",
    "ncbi_link": "Venus: 
Rod: 9735"
  },
  {
    "caption": "Immunofluorescence analysis of ZW10 and Mad1 upon depletion of Rod. Scale bar, 5 μm.",
    "ncbi_link": "Rod: 9735"
  },
  {
    "caption": "Quantification of kinetochore intensities of the indicated proteins in control or Rod depleted cells with the signal normalized to CREST levels and Bub1 pSpT normalized to Bub1. Bar indicates mean and standard error of mean is shown by line. At least 200 kinetochores from 10 cells were analyzed and representative result from at least 2 independent experiments is shown.",
    "ncbi_link": "Rod: 9735"
  },
  {
    "caption": "Time from NEBD to mitotic exit in control depleted, Rod depleted, Bub1 depleted and Rod and Bub1 co-depleted HeLa, U2OS and RPE1 cells. Cells were treated with nocodazole.",
    "ncbi_link": "Bub1: 699
Rod: 9735"
  },
  {
    "caption": "Representative still images of unperturbed mitosis for parental cells, Rod C cells and Rod CR cells with time in minutes indicated. CFP-Histone 3 was used here as the chromosome marker. Scale bar, 5 μm.",
    "ncbi_link": "Rod: 9735"
  },
  {
    "caption": "Estimated protein levels of Bub1 in the indicated conditions relative to parental cell lines. In Bub1 CR we only detected one peptide from three purifications. Standard deviation indicated.",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "Representative still images of unperturbed mitosis for parental cells, Bub1 C cells and Bub1 CR cells with time in minutes indicated. CFP-Histone 3 was used as the chromosome marker. Scale bar, 5 μm.",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "Localization of Venus-tagged Mad1 in parental HeLa cells, Bub1 CR cells and Rod CR cells in the presence of nocodazole. Scale bar, 5 μm.",
    "ncbi_link": "Bub1: 699
Rod: 9735"
  },
  {
    "caption": "A HeLa cell line stably expressing Mad1-BirA was depleted of Rod and synchronized in mitosis using thymidine and nocodazole. Biotin was added to media where indicated and biotinylated proteins were purified and analyzed by western blot with the indicated antibodies. Representative of 2 independent experiments.",
    "ncbi_link": "Rod: 9735"
  },
  {
    "caption": "Cells depleted of Rod using RNAi and transfected with the indicated Bub1 constructs. (D) Representative immunofluorescence images of cells stained for YFP and Mad1 in each condition. Scale bar, 5 μm.",
    "ncbi_link": "Bub1: 699
Rod: 9735"
  },
  {
    "caption": "Cells depleted of Rod using RNAi and transfected with the indicated Bub1 constructs. Mad1 kinetochore levels were measured and normalized to Bub1 (YFP) level. Bar indicates mean and standard error of mean is shown by line. At least 200 kinetochores from 10 cells were analyzed and representative result from at least 2 independent experiments is shown.",
    "ncbi_link": "Bub1: 699
Rod: 9735"
  },
  {
    "caption": "Bub1 CR cells complemented with the indicated Bub1 constructs and time from NEBD to exit in nocodazole measured by time-lapse microscopy. Mean (red line) and standard error of mean (black bar) indicated.",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "Kinetochore levels of Mad1 in Bub1 CR cells complemented with the indicated YFP tagged Bub1 constructs. Mad1 levels are normalized to YFP signal. Bar indicates mean and standard error of mean is shown by line. At least 200 kinetochores from 10 cells were analyzed and representative result from at least 2 independent experiments shown.",
    "ncbi_link": "YFP: 
Bub1: 699"
  },
  {
    "caption": "Still images of unperturbed mitosis of HeLa cells transfected with Venus-Bub1 4xCD1. CFP-Histone 3 was used as the chromosome marker (the middle panel) and Venus-Bub1 4xCD1 was shown in the bottom panel. Scale bar, 5 μm.",
    "ncbi_link": "Venus: 
Bub1: 699"
  },
  {
    "caption": "HeLa cells transfected with the indicated Bub1 constructs and time from NEBD to exit determined during an unperturbed mitosis. The time from NEBD to exit was analyzed in each condition. Mean (red line) and standard error of mean (black bar) indicated. (Mann Whitney test, ns: non-significant). A representative result from at least 3 independent experiments is shown.",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "Localization of Venus-Rod during unperturbed mitosis in control depleted or Bub1 depleted cells.",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "HeLa cells were depleted of Bub1 using RNAi and complemented with indicated Venus-Bub1 constructs. Immunofluorescence images were shown for Bub1 and ZW10 localization. Quantification of Bub1 and ZW10 kinetochore levels normalized to CREST in the indicated conditions.",
    "ncbi_link": "Venus: 
Bub1: 699"
  },
  {
    "caption": "HeLa cells were depleted of Bub1 using RNAi Immunofluorescence images were shown for Bub1 and ZW10 localization. Quantification of Bub1 and ZW10 kinetochore levels normalized to CREST in the indicated conditions. with the indicated Bub1 fusion proteins",
    "ncbi_link": "Bub1: 699"
  },
  {
    "caption": "(A) Cell proliferation for PC3 cells transfected with siSCR or siCLU monitored in real time for 60h with SP Dynamic Xcelligence system (Voltage 2.5 K). Error bars represent mean ± SEM, n=4. Slopes compared by ANCOVA test, p<0.0001.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(B) Left panel: Cell cycle profile of PC3 cells transfected with siSCR or siCLU. Right panel: Percentage quantification of variation in G1, S and G2/M phases. Error bars represent mean ± SEM, n=3, **p<0.01 by paired Student's t-test. (G2/M population p= 0.0058; G1 p=0.008.). Inset: Western blot with CLU antibody in PC3 cells after CLU silencing. Vinculin was used as loading control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(C) Left panel: RNA-Microarray analysis comparing PC3 cells transfected with siCLU versus siSCR and Kinexus phosphokinome microarray analysis comparing LNCaP-transfected with siCLU versus siSCR. Target genes expression is shown as fold change relative to siSCR, p ≤0.05 by an unpaired t-test for all the genes listed. Central panel: Venn diagram to graphically illustrate the overlap of mRNA and proteins involved in the regulation of mitosis in both transcriptome and phosphokinome analysis. The comparison of these 2 experiments shows modification of 4 mitosis regulators. Right panel: Western blot validating the expression levels of target proteins.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(A) Real-time PCR for CLU and Cdc25C in three different prostate cancer cell lines. Target genes expression was calculated relative to GAPDH and normalized to siSCR. Error bars represent mean ± SD, n=3.",
    "ncbi_link": "GAPDH: 
Cdc25C: 995
CLU: 1191"
  },
  {
    "caption": "(B) Western blot for CLU and Cdc25C after siSCR or si CLU transfection in the same prostate cancer cell lines as in A. Vinculin was used as loading control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(C) Western blot for CLU and Cdc25C in PC3 cells after transfection with siSCR or siCLU followed by transfection with CLU or empty expression plasmid for additional 48h. Vinculin was used as loading control",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(B) Western blot with the correspondent quantification of protein levels (left) and real time PCR (right) from untreated LNCaP xenografts harvested at endpoint. The negative correlation between CLU-RNA and Cdc25C-RNA ΔΔCT values was calculated using a spearman test (rho=-0.86; p=0.0107).",
    "ncbi_link": "Cdc25C: 995
CLU: 1191"
  },
  {
    "caption": "(C) Duolink proximity ligation assay between Cdc25C and CLU in PC3 cells. Confocal microscopy was used to detect the interaction (red dots). DNA was counterstained with DAPI (blue). PC3 cells transfected with siCLU were used as a negative control. Scale bar represent 10 µm.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(A) Left panel: Western blot for CLU, Cdc25C, Cdc25C-T48, Cdc25C S216 and Cdc25C S198 in PC-3 cells after siSCR or siCLU transfection, synchronization and nocodazole release at indicated time points. Vinculin was used as loading control. Right panel: Immunofluorescence microscopy for Cdc25C-T48 in PC3 cells after siSCR or siCLU transfection. DNA was counterstained with (DAPI) (blue). Scale bar represents 10 µm.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(B) Western blot for CLU, Cdc25C-T48, Cdk1 and PP2A in PC3 cells after siSCR or siCLU transfection and after synchronization followed by treatment with or without okadaic acid (OA) (100 nM) for 12 hours. Proteins were extracted 15 min after nocodazole release. Vinculin was used as loading control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(D) PP2A phosphatase activity measurement in PC3 cells after siSCR or siCLU transfection, synchronization and nocodazole release at indicated time points. Error bar represent mean ± SEM, n=3, ** p<0.01 (p=0.0025) by ANOVA followed by Bonferroni's post hoc comparisons. Cells treated with no peptide were used as a negative control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(A) Western blot for CLU, Cdk1 Y15, Cdk1 and Wee1 in PC-3 cells after siSCR or siCLU transfection followed by synchronization and nocodazole release at indicated time points. Vinculin was used as loading control",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(B) Wee1 expression level was evaluated in PC3 cells after CLU silencing by real-time PCR. Error bar represent mean ± SEM, n=3, *** p<0.001 (p=0.0001) by unpaired t-test followed by Welch's correction.",
    "ncbi_link": "CLU: 1191
Wee1: 7465"
  },
  {
    "caption": "(C) FACS analysis showing percentage of the PC3 cells positive for phosphohistone H3 after transfection with siSCR or siCLU in presence and absence of Wee1 inhibitor, MK-1775. Error bar represent mean ± SEM, n=3, ****p<0.0001 by Mann-Whitney",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(D) Western blot for CLU, Wee1, Cdk1 Y15, Cdk1 and Cyclin B1 in PC3 cells after transfection with siSCR or siCLU followed by synchronization and treatment with or without MK-1775, a specific Wee1 inhibitor, for 12 hours. Cells were harvested at different time points after nocodazole release. Vinculin was used as loading control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(A) Cabazitaxel IC50 calculation using WST1 assay in PC3 cells after transfection with siSCR or siCLU (left), and SCR or OGX-011 (right) followed by 72h of cabazitaxel treatment. Percentage of surviving cells was calculated relative to control. Error bar represent mean ± SEM, n=3. Inset: Western blot was performed to verify CLU knockdown in cells.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(B) Western blot for CLU, Cdc25C, Cdc25C-T48, Cdk1, Cdk1-Y15 and Wee1 in IGRCaP-1 and PC3 parental (WT) or cabazitaxel-resistant (R-caba) cells as well as for PC3-R-caba cells transfected with siSCR or siCLU. Vinculin was used as loading control.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "(D) Cell survival measured using WST1 in PC3 resistant cells after transfection with siSCR or siCLU followed by treatment with cabazitaxel (10 nM; C10), MK-1775 (10 nM; MK10) or both for 72 hours. .Error bar represent the mean ± SEM, n=3, *** p<0.001 by one way ANOVA followed by Bonferroni's post hoc correction.",
    "ncbi_link": "CLU: 1191"
  },
  {
    "caption": "A. Ovaries from control heterozygous Rpp3018.2 flies (left), homozygous Rpp3018.2 or transheterozygous Rpp3018.2/Rpp30PE flies (middle) and homozygous Rpp3018.2 carrying a copy of ubiRpp30GFP transgene (right). Scale bar, 100µm.",
    "ncbi_link": "GFP: 
Rpp30: 44392"
  },
  {
    "caption": "E. Rpp30-dependent early oogenesis arrest is restored by expression of Rpp30GFP transgene in two different genetic backgrounds: Left. Homozygous Rpp3018.2 ovariole expressing ubiquitous ubiRpp30GFP (st, stage). Right. Transheterozygous Rpp3018.2/Rpp30PE ovarioles overexpressing germline specific nanosGal4,UASRpp30GFP. Note follicular somatic cells with no Rpp30GFP expression (arrowhead). Magnifications show nuclear Rpp30 localization, Rpp30 perinuclear foci (arrows), and Orb (a specific oocyte marker). Scale bar, 10µm.",
    "ncbi_link": "Gal4,UAS: 
Rpp30: 44392"
  },
  {
    "caption": "F. flp/FRT clones mutant for Rpp3018.2specifically in the germline (star) and/or the follicular cells (arrows) are detected by the absence of GFP. Magnifications show mutant oocytes with Orb mislocalization next to the karyosome (dotted circle) instead of being localized to the posterior, as seen in stage 3 (st.3) wild-type clones. Scale bar, 10µm.",
    "ncbi_link": "Rpp30: 44392"
  },
  {
    "caption": "Figure 2. Rpp30 is required for pre-tRNA processing.Whole fly RNA extracts were used to study tRNA processing by Northern Blot. Top box : the three different probes used are depicted : 5' and 3' probes (red and green, respectively) can detect full pre-tRNAs and tRNAs intermediates, but will not detect mature tRNAs. An Internal Probe (IP, blue) corresponding to the anti-codon region was used to detect all non-mature and mature tRNAs. The genotypes used in this experiment are numbered at the bottom (1-6). Northern Blot panels: tRNA-his 5' probe (top), tRNA-his 3' probe (middle) and tRNA-his IP (bottom). U6 probe was used as loading control.",
    "ncbi_link": "U6: 
Rpp30: 44392"
  },
  {
    "caption": "A. Rpp3018.2 homozygous early oogenesis arrest is partially rescued by p53 mutation. Scale bar,100μm.",
    "ncbi_link": "p53: 2768677
Rpp30: 44392"
  },
  {
    "caption": "B. Early oogenesis arrest found in Rpp3018.2 homozygous ovaries is rescued by chk2 mutation (Rpp3018.2 , mnkp6 and Rpp3018.2/ Rpp30PE, mnkp6). Scale bar, 100μm. Star: example of one rescued stage 9 egg chamber. Arrow: example of non-rescued egg chambers.",
    "ncbi_link": "chk2: 35288
Rpp30: 44392"
  },
  {
    "caption": "C. Germline clones mutant for Rpp3018.2 were immunostained for PCNA (red). DAPI is in blue. Magnifications: PCNA signal in a control or mutant nurse cell. Scale bar, 10μm.",
    "ncbi_link": "Rpp30: 44392"
  },
  {
    "caption": "D. Germline clones mutant for Rpp3018.2 were immunostained for Brf (pol-III) (red). DAPI is in blue. A Z-projection of Brf staining is shown. The arrow points Brf aggregates in a mutant chamber. Scale bar, 10μm.",
    "ncbi_link": "Rpp30: 44392"
  },
  {
    "caption": "E. Early oogenesis arrest found in Rpp3018.2 homozygous ovaries is partially rescued by claspin mutation (Rpp3018.2; claspinEP/TM3). Scale bar, 100μm.",
    "ncbi_link": "claspin: 326205
Rpp30: 44392"
  },
  {
    "caption": "G. Top panel. Early oogenesis arrest found in Rpp30182./PEtransheterozygous ovaries is rescued by sqd-S-HAoverexpression. Scale bars: 100µm. Low panel. Rpp3018.2/PE ; sqd-S-HA/sqd-S-HA ovaries were dissected and stained for Orb (green), HA (squid, red) and DAPI (blue). Scale bar, 10µm.",
    "ncbi_link": "Rpp30: 44392
sqd: 41666"
  },
  {
    "caption": ". D. Nuage specific markers (Aub, Ago3 and Mael) are shown in stage 3 wild-type and germline mutant clones for Rpp3018.2. Scale bar, 10µm.",
    "ncbi_link": "Rpp30: 44392"
  },
  {
    "caption": "E-H. Double mutant ovaries for Rpp30 and chk2 (Rpp3018.2, mnkp6) rescued the specific and general piRNA populations, nuage morphology and the characteristic ping-pong signal. Scale bar, 10µm.",
    "ncbi_link": "chk2: 35288
Rpp30: 44392"
  },
  {
    "caption": "D. Testes from control heterozygous, transheterozygous Rpp3018.2/Rpp30PE or aubHN/QC42 were fixed and stained for Stellate crystal formation. Z-projections are shown.",
    "ncbi_link": "aub: 34524
Rpp30: 44392"
  },
  {
    "caption": "  Quantification of mRNAs in ASPC-1 cells untreated or treated with OMP 80 µg/ml, 5-FU 5 µg/ml or the combination of both was performed at different time points throughout 24 hours, and the means of three replicates are shown for every time point. The stars indicate significant differences after 24 hours compared to control. The pro-apoptotic bad-mRNA was upregulated after 5-FU- and 5-FU+OMP-treatment. The antiapoptotic bcl-2 mRNA was downregulated by 5-FU and bcl-XL by 5-FU+OMP. OMP led to downregulation of bad and survivin and to upregulation of the mdr-1mRNA.  ",
    "ncbi_link": "mdr-1: 5243
bad: 572
bcl-2: 596
bcl-XL: 598
survivin: 332"
  },
  {
    "caption": "  mRNA quantification in MiaPaCa-2 cells untreated or treated with OMP 80 µg/ml, 5-FU 5 µg/ml or the combination of both was performed at different time points throughout 24 hours, and the means of three replicates are shown for every time point. While the mdr-1 mRNA is not signicantly changed, the vATPase mRNA is upregulated in the 5-FU+OMP group after 24 hours compared to control.  ",
    "ncbi_link": "vATPase: 
mdr-1: 5243"
  },
  {
    "caption": "E Levels of LMs and PGE2 released by macrophages in presence of CVF, CLys and CSN Additionally, macrophages were lysed and gene expression of PTGS2, PTGES, ALOX5, ALOX15 and MaR1 quantified by RT-PCR.",
    "ncbi_link": "ALOX15: 246
ALOX5: 240
PTGES: 9536
PTGS2: 5743
MaR1: 388015"
  },
  {
    "caption": "(E) ASS1 expression from the MILE study. The dotted line revers for average of Healthy Bone Marrow. Data information: For statistical analysis, an ordinary one-way ANOVA with Dunnett's correction for multiple comparisons was performed a Kruskal-Wallis test was performed on E with **** referring to P<.0001 in E.",
    "ncbi_link": "ASS1: 445"
  },
  {
    "caption": "(B) Immunogold electron micrograph of GFP  or ORF6-GFP  expressed HeLa  cells. Blue arrows mark ORF6-GFP  dots are enriched on the surface of LDs. Green arrows mark GFP  dots are distributed in the cytoplasm. Scale bar represents 500 nm.",
    "ncbi_link": "GFP: 
ORF6: 43740572"
  },
  {
    "caption": "(C, D and E) HeLa  cells stable expressing ORF6-Flag  were treated with or without 200 μM OA  for 12 h, then fixed and stained  with anti-Flag  (red). Initial LDs  were labeled with GFP-GPAT4152-208 (green), mature LDs  were labeled with BODIPY-493/503 (green) or GFP-Plin2  (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(B) Analysis of the homodimerization  of ORF6  by cross-linking with DSS. HEK293T  cells expressing ORF6-Flag  were treated with 0, 0.1, 0.2 and 0.3 mM DSS  for 30 min. Cell lysates were analyzed via WB.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(D) The indicated Flag  tagged ORF6  or its mutants were co-expressed in HEK293T  cells with HA  tagged ORF6. Protein interactions   were analyzed by immunoprecipitation  with anti-Flag  beads and immunoblotting  analysis.",
    "ncbi_link": "Flag: 
HA: 
ORF6: 43740572"
  },
  {
    "caption": "(F) HEK293T  cells were transfected with ORF6-Flag  or ΔNTD-Flag  or ΔAH1-Flag  or ΔAH2-Flag  and were treated with 0.1 mM DSS  for 30 min. Cell lysates were analyzed via WB.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(G) HeLa  cells were transfected with ORF6-Flag  or indicated mutants and were treated with 200 μM OA  for 12 h, and then fixed and stained  with anti-Flag  (red). LDs  were labeled with BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(A) HeLa  cells were transfected with vector or ORF6-Flag  for 24 h, and then treated with 200 μM OA  for indicated times. Cells were fixed and stained  with anti-Flag  (green). LDs  were labeled with LipidTox Deep Red  (red). The nuclei  were stained  with DAPI. Cells were imaged by  confocal microscopy. Scale bar represents 10 μm. White ROIs indicate cells expressing ORF6  and yellow ROIs indicate the cells without ORF6 expression.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(D) HeLa  cells stable expressing vector or ORF6-Flag  were treated or untreated with 50 μM ATGL  inhibitor (ATGLi) for 24 h, and then were fixed and stained  with anti-Flag  (red). LDs  were labeled with  BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm. (E) Mean number of LDs  in each cell in (D) was counted from 25 cells of three independent experiments. Two-tailed Unpaired Student's t-test, ***p < 0.001, ****p < 0.0001. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(H) HeLa  cells stable expressing vector or ORF6-Flag  were treated or untreated with 50 μM ATGL  inhibitor, along with DMSO  or 1 μM DGAT1  inhibitor (DGAT1i) or/and 2 μM DGAT2  inhibitor (DGAT2i) for 24 h. LDs  were labeled with BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm. (I) Mean number of LDs in each cell in (H) was counted from 35 cells of three independent experiments. Two-tailed Unpaired Student's t-test, ***p < 0.001, ****p < 0.0001, ns means no significance. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(A) Subcellular fractions were isolated from GFP  or ORF6-GFP  over-expressed cells. Calnexin  represent the ER, Plin2  represent LDs, Rab11  represent endosomes, VDAC  represent mitochondria, and Tubulin  represents cytoplasm, respectively.",
    "ncbi_link": "GFP: 
ORF6: 43740572"
  },
  {
    "caption": "(E) ORF6-Flag  or the mutants were co-expressed with mCheey-RAMP4. Cells were treated with 200 μM OA  for 12 h, and then fixed and stained  with anti-Flag  (red). The ER  was visualized with mCheey-RAMP4  (red). LDs  were labeled with LipidTOX Deep Red (white). Cells were imaged by confocal microscopy. Scale bar represents 10 μm.",
    "ncbi_link": "Flag: 
mCheey: 
ORF6: 43740572
RAMP4: 27230"
  },
  {
    "caption": "(J) HeLa  cells stable expressing ORF6-Flag  were transfected with si-BAP31  and/or si-USE1  for 24 h, and were further treated with 50 μM ATGL  inhibitor for 24h. Cells were fixed and stained  with anti-Flag  (red). LDs  were labeled with BODIPY-493/503 (green). The nuclei  were stained  with DAPI. Cells were imaged by  confocal microscopy. Scale bar represents 10 μm. (K) Mean number of LDs  in each cell in (J) was counted from 25 cells of three independent experiments. Two-tailed Unpaired Student's t-test, *p < 0.05, **p < 0.01. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
BAP31: 10134
ORF6: 43740572
USE1: 55850"
  },
  {
    "caption": "(L)  SARS-CoV-2-infected  Vero-E6  cells were transfected with control, or si-BAP31  and/or si-USE1  for 48 h. Cell lysates were analyzed via WB. Supernatants were determined by  plaque assays. Virus titer values represent mean ± SD for three independent replicates. Two-tailed Unpaired Student's t-test, ****p < 0.0001, ns means no significance. Error bars represent the mean ± SD.",
    "ncbi_link": "BAP31: 103232989
USE1: 103234122"
  },
  {
    "caption": "(A) HeLa  cells were transfected with vector or ORF6-Flag  for 12 h and treated with 200 μM OA  for another 12 h, the medium was removed and replaced with fresh complete culture containing 1 μM DGAT1  inhibitor and 2 μM DGAT2  inhibitor for 24 h. Meanwhile, 50 μM ATGL  inhibitor or 100 μM Chloroquine  (CQ) was added and allowed to incubate for 24 h or 4 h to block lipolysis  or lipophagy, respectively. Cells were fixed and stained  with anti-Flag  (red). LDs  were labeled with BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm. White ROIs indicate cells expressing ORF6  and yellow ROIs indicate the cells without ORF6 expression.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(C) HEK293T  cells were transfected with ORF6-Flag. Protein interactions  were detected by immunoprecipitation  with anti-Flag  beads and immunoblotting  analysis with ATGL, HSL, and CGI58 antibodies.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(H and I) The effect of ORF6-Flag  or the ΔNTD mutant on the interactions  of Flag-ATGL  with GFP-Plin2  or GFP-UBXD8  was analyzed by immunoprecipitation.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(K and L)  Vero-E6  cells were transfected with Flag-ATGL  and GFP-Plin2  or GFP-UBXD8  for 24 h and infected or non-infected with SARS-CoV-2 for 24 h. Protein interactions  were analyzed by immunoprecipitation  with anti-GFP beads and immunoblotting  analysis.",
    "ncbi_link": "ATGL: 
Flag: 
GFP: 
UBXD8: 23197
Plin2: 123"
  },
  {
    "caption": "(C) Representative transmission electron micrograph  of ORF6-Flag  stable expressing or vector HeLa  cells upon OA  treatment. Red arrows mark the contact sites between LDs  and mitochondria. M, mitochondria. LD,  lipid droplets. Scale bar represents 1 μm. (D) The number of mitochondria-LD  contacts per cell was counted from 20 cells. The number of mitochondrial  engaged in mitochondrial-LD  contact per LD  in (C) was counted from 20 LDs. Two independent experiments. Two-tailed Unpaired Student's t-test, ****p < 0.0001. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(H) Cos7  cells expressing ORF6-Flag  and vector were treated with 200 μM OA  for 12 h, and then were fixed and stained  with anti-Flag  (white) and anti-Tom20  (red). Tom20  represents mitochondria  marker. LDs  were labeled with BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(L) Seahorse FAO assays  to examine the oxidation of endogenous FAs  in vector, or ORF6-Flag  or ORF64Q-Flag  over-expressed HeLa  cells. Three biological replicates were performed with similar results. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
ORF6: 43740572"
  },
  {
    "caption": "(N) Vero-E6 cells stable expressing GFP  or GFP-Plin5  or GFP-Plin5Δ443-463 were infected with SARS-CoV-2 for 24 h. Cell viability was analyzed. Cell lysates were analyzed via WB. Supernatants were determined by plaque assays. Virus titer  values represent mean ± SD for three independent replicates. Two-tailed Unpaired Student's t-test, **p < 0.01, ns means no significance. Error bars represent the mean ± SD.",
    "ncbi_link": "GFP: 
Plin5: 440503"
  },
  {
    "caption": "(C) HeLa  cells were transfected with negative, or si-MTX1, or si-MTX2, or si-SAMM50  for 24 h and further transfected with ORF6-GFP  24 h. Subcellular fractions were isolated from cells. VDAC1  and ATP5A1  represent mitochondria  markers, Tubulin  represents cytosolic  marker.",
    "ncbi_link": "GFP: 
MTX1: 4580
MTX2: 10651
ORF6: 43740572
SAMM50: 25813"
  },
  {
    "caption": "(D) HeLa  cells were transfected with negative or si-MTX1  and si-MTX2 for 24 h and further transfected with ORF6-GFP  24 h. Subcellular fractions were isolated from cells. VDAC1  and ATP5A1  represent mitochondria  markers, Tubulin  represents cytosolic  marker.",
    "ncbi_link": "GFP: 
MTX1: 4580
MTX2: 10651
ORF6: 43740572"
  },
  {
    "caption": "(F) Cos7  cells expressing ORF6-Flag  were transfected with negative or si-MTX1/si-MTX2/si-SAMM50  (Triple KD) for 36 h and treated with 200 μM OA  for another 12 h. Cells were fixed and stained  with anti-Flag  (white) and anti-Tom20  (red). Tom20  represents mitochondria  marker. LDs  were labeled with BODIPY-493/503 (green). Cells were imaged by confocal microscopy. Scale bar represents 10 μm. (G) Quantification of average number of LD-mitochondria  contacts per LD  from (F). 25 cells (Negative), 50 cells (Triple KD) from three independent experiments were calculated. Two-tailed Unpaired Student's t-test, ****p < 0.0001. Error bars represent the mean ± SD.",
    "ncbi_link": "Flag: 
MTX1: 4580
MTX2: 10651
ORF6: 43740572
SAMM50: 25813"
  },
  {
    "caption": "HeLa cells overexpressing the HA-tagged MICU1 WT, MICU1 S124D or MICU1 S124A mutants were stained for HA or HSP60 (mitochondrial marker). Merged images are indicated (merge). Scale bar 10 μm",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Representative images of the 2mt-GCaMP6m 474/410 ratio of ShMICU1 HeLa stable cells expressing an empty vector (ctrl) or the MICU1 WT, MICU1 SD, and MICU1 SA. Scale bar 10 μm",
    "ncbi_link": "MICU1: 10367
MICU1: 216001"
  },
  {
    "caption": "Resting mitochondrial calcium levels, evaluated through ratiometric imaging of the mitochondrial targeted GCaMP6m, in ShRNA control (plko) or ShRNA MICU1 HeLa stable clone cells transfected with the indicated constructs (n=5 independent experiments; 55-67cells)",
    "ncbi_link": "plko: 
MICU1: 10367"
  },
  {
    "caption": "Representative kinetics (E) and analysis (F) of aequorin-based [Ca2+]m measurements in ShRNA MICU1 HeLa stable clone cells transfected with the indicated constructs and challenged with 20 μM 2,5-di-tert-butylhydroquinone (TBHQ) in the absence of extracellular Ca2+ (n=3 independent experiments)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Representative kinetics (G) and analysis (H) of aequorin-based [Ca2+]m measurements in intact ShRNA MICU1 HeLa stable clone cells transfected with the indicated constructs and challenged with 10 μM cyclopiazonic acid (CPA) in the presence of 100 μM EGTA (n=3 independent experiments)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Resting mitochondrial calcium levels, evaluated through ratiometric imaging of the mitochondrial-targeted GCaMP6m, in MICU1-KO cells generated using the CRISPR/Cas9 technique and transfected with the indicated constructs (n=3 independent experiments; 30-56 cells)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Representative kinetics (K) and analysis (L) of aequorin-based [Ca2+]m measurements in intact MICU1-KO cells generated using the CRISPR/Cas9 technique, transfected with the indicated constructs and challenged with 20 μM TBHQ in the absence of extracellular Ca2+ (n=3 independent experiments.)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Representative kinetics (M) and analysis (N) of aequorin-based [Ca2+]m measurements in intact MICU1-KO cells generated using the CRISPR/Cas9 technique, transfected with the indicated constructs and challenged with 10 μM CPA in the presence of 100 μM EGTA (n=3 independent experiments).",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Hek293T cells were transfected with the GFP-tagged wild-type (WT) MICU1 and then treated with 1 μM rapamycin (Rapa.) alone for 4 h or in combination with the Akt inhibitor triciribine (10 μM). GFP-MICU1 immunocomplexes were precipitated with a GFP antibody and analyzed with PAS (phospho-Akt substrate) and phosphorylated (S473) Akt (p-Akt) antibodies by western blotting",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Hek293T cells were transfected with either the GFP-tagged wild-type (WT) MICU1 or MICU1 S124A-GFP mutant. MICU1-GFP immunocomplexes were precipitated with a GFP antibody and analyzed with PAS (phospho-Akt substrate) antibody by western blotting.",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Mitochondrial preparations of both Hek293T (left) and HeLa (right) cells transiently transfected with an HA-tagged constitutively active Akt T308D/S473D (Akt D/D) construct were analyzed by western blotting. GAPDH: cytosolic marker; TIM23: mitochondrial marker",
    "ncbi_link": "Akt: 11651"
  },
  {
    "caption": "Resting mitochondrial calcium levels in the control (ctrl) and Akt D/D-expressing HeLa cells evaluated by ratiometric imaging of the mitochondrial-targeted GCaMP6m (n=4 independent experiments; 44-49 cells)",
    "ncbi_link": "Akt: 11651"
  },
  {
    "caption": "Schematic model of the HA-tagged constitutively active Akt form targeted to the mitochondrial intermembrane space (mt-Akt D/D). Both the expression and the mitochondrial localization of the chimera were assessed by immunofluorescence. TOM20 was used as a mitochondrial marker. Merged images are indicated (merge). Scale bar 10 μm",
    "ncbi_link": "Akt: 11651"
  },
  {
    "caption": "Resting mitochondrial calcium levels in control (ctrl) and mitochondrial-targeted Akt D/D (mt-Akt D/D)-expressing HeLa cells, evaluated through ratiometric imaging of the mitochondrial-targeted GCaMP6m (n=4 independent experiments; 43-47 cells)",
    "ncbi_link": "Akt: 11651"
  },
  {
    "caption": "Resting mitochondrial calcium levels in ShRNA MICU1 HeLa stable cells transfected with the indicated constructs and evaluated through ratiometric imaging of the mitochondrial targeted GCaMP6m (n=3 independent experiments; 38-50 cells)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Representative kinetics (H) and analysis (I) of aequorin-based [Ca2+]m measurements in permeabilized ShRNA MICU1 HeLa stable cells transfected with the indicated constructs and challenged with 400 nM buffered [Ca2+] (n=3 independent experiments).",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Western blot analysis of ShRNA MICU1 HeLa stable cells transfected with the indicated constructs. pre-MICU1: precursor form of MICU1; m-MICU1: mature form of MICU1",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Western blot analysis of ShRNA MICU1 HeLa stable cells transfected with the indicated constructs. Where indicated, the cells were treated with 5 μM MG132 for 4 h. pre: precursor; int: intermediate; m: mature form",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Western blot analysis of the supernatant (S) and insoluble pellet (P) fractions of ShRNA MICU1 HeLa cell mitochondria transfected with the indicated constructs, following carbonate extraction at pH 10. The established integral membrane protein TIM23 and the soluble protein cytochrome c (Cyt. c) were analyzed as markers. The cells were treated with 5 μM MG132 for 4 h before fractionation",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Western blot analysis of the supernatant (S) and insoluble pellet (P) fractions of ShRNA MICU1 HeLa cell mitochondria transfected with MICU1 WT-HA or MICU1 SD-HA, together with MCU-flag and EMRE constructs, following carbonate extraction at pH 7.4, pH 10.5, pH 11.5 or pH 12.5. The cells were treated with 5 μM MG132 for 4 h before fractionation",
    "ncbi_link": "MCU: 215999
MICU1: 10367
MICU1: 216001
EMRE: 69029"
  },
  {
    "caption": "ShRNA MICU1 HeLa stable cells were transfected with the indicated constructs. Cells were incubated with 50 μg/ml cycloheximide (CHX) for the indicated times, collected and subjected to western blotting analysis as indicated. In the graph, the amount of HA (MICU1), both WT and mutants, is represented relative to the amount at time 0. (n=3 independent experiments)",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "ShRNA MICU1 HeLa stable cells were transfected with the indicated constructs. Cells were harvested, and total protein was extracted and subjected to western blotting analysis with the indicated antibodies. Immunoblotting was performed under reducing (with the presence of DTT) or non-reducing (non-red) conditions (without DTT). Cells were treated with 5 μM MG132 for 4 h before lysis",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Resting mitochondrial calcium levels, evaluated through ratiometric imaging of the mitochondrial targeted GCaMP6m, in ShRNA MICU1 HeLa stable clone cells transfected with the indicated constructs (n=3 independent experiments; 46-54 cells).",
    "ncbi_link": "MICU1: 10367"
  },
  {
    "caption": "Western blot analysis of endogenous MICU1 levels in HeLa cells upon silencing of IMMP1L and/or IMMP2L. int: intermediate; m: mature form",
    "ncbi_link": "IMMP1L: 196294
IMMP2L: 83943"
  },
  {
    "caption": "Western blot analysis of HeLa cells transfected with the indicated constructs and silenced with IMMP1L and/or IMMP2L. int: intermediate; m: mature form. Cells were treated with 5 μM MG132 for 4 h before lysis",
    "ncbi_link": "IMMP1L: 196294
IMMP2L: 83943"
  },
  {
    "caption": "Western blot analysis of the supernatant (S) and insoluble pellet (P) fractions of control or IMMP1L-silenced HeLa cell mitochondria following carbonate extraction at pH 10. The established integral membrane protein TIM23 and the soluble protein cytochrome c (Cyt. c) were analyzed as markers",
    "ncbi_link": "IMMP1L: 196294"
  },
  {
    "caption": "Western blot analysis of the supernatant (S) and insoluble pellet (P) fractions of control or IMMP1L-silenced HeLa cell mitochondria transfected with HA-tagged MICU1 WT following carbonate extraction at pH 10. The established integral membrane protein TIM23 and the soluble protein cytochrome c (Cyt. c) were analyzed as markers. pre: precursor; int: intermediate; m: mature form. Cells were treated with 5 μM MG132 for 4 h before lysis",
    "ncbi_link": "IMMP1L: 196294
MICU1: 216001"
  },
  {
    "caption": "Control or IMMP1L-silenced HeLa cells were transfected with HA-tagged MICU1 WT. Cells were incubated with 50 μg/ml cycloheximide (CHX) for the indicated times, collected and subjected to western blotting analysis as indicated. In the graph, the amount of HA (MICU1) is represented relative to the amount at time 0. (n=3 independent experiments)",
    "ncbi_link": "IMMP1L: 196294
MICU1: 216001"
  },
  {
    "caption": "Representative kinetics (F) and analysis (G) of aequorin-based [Ca2+]m measurements in control or IMMP1L-silenced HeLa cells challenged with 10 μM cyclopiazonic acid (CPA) in the presence of 100 μM EGTA (n=3 independent experiments)",
    "ncbi_link": "IMMP1L: 196294"
  },
  {
    "caption": "Resting mitochondrial calcium levels, evaluated through ratiometric imaging of the mitochondrial targeted GCaMP6m, in control or IMMP1L-silenced HeLa cells (n=3 independent experiments; 37-55 cells).",
    "ncbi_link": "IMMP1L: 196294"
  },
  {
    "caption": "Lung cancer cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with a GFP antibody and analyzed with a PAS (phospho-Akt substrate) antibody by western blotting",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Melanoma cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with a GFP antibody and analyzed with PAS (phospho-Akt substrate) antibody by western blotting",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Glioblastoma cells were transfected with the GFP-tagged WT MICU1. MICU1-GFP immunocomplexes were precipitated with GFP antibody and analyzed with PAS (phospho-Akt substrate) antibody by western blotting",
    "ncbi_link": "MICU1: 216001"
  },
  {
    "caption": "Representative images (J) and analysis (K) of MitoSOX-based ROS measurements in ShRNA MICU1 HeLa stable cells stably expressing either MICU1 S124D (SD) or MICU1 S124A (SA) (n=3 independent experiments). Scale bar 10 μm. f.a.u.: fluorescence arbitrary unit",
    "ncbi_link": "MICU1: 10367
MICU1: 216001"
  },
  {
    "caption": "ShRNA MICU1 HeLa stable cells stably expressing either MICU1 S124D (SD) or MICU1 S124A (SA) were treated with 500 μM H2O2 alone or in combination with the ROS scavenger Tempol and analyzed by western blotting as indicated. l. e.: long exposure.",
    "ncbi_link": "MICU1: 10367
MICU1: 216001"
  },
  {
    "caption": "(g) Fold change in the  expression  of HBE1 or HBG1-2  transcripts ± SEM normalized to  KLF1 in CFUs obtained from HE  cells treated with UK5099 (10 µM) or  DCA (3 mM) relative to non-treated cells (n=3 biological replicates, paired t-test). Data information: ns, not significant, *p<0.05, **p<0.01, ***p<0.001",
    "ncbi_link": "HBE1: 3046
HBG1: 3047
KLF1: 10661"
  },
  {
    "caption": "(d)  HE  cells were transduced with shScrambled (shScr) or shLSD1 with or without UK5099 (10 µM) the day after the sort  and day 3  CD43+/GPA+ cell frequencies ± SEM relative to shScr are presented (n=3 biological replicates 1-2 technical replicates each, one-way ANOVA test). Data information: ns, not significant, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "(n) Dot plots showing gene expression  levels of NOTCH1, JAG1 and HES1 detected by  scRNAseq and based on percent expressed (size of the dots) and average level of  expression (color intensity).",
    "ncbi_link": "HES1: 3280
JAG1: 182
NOTCH1: 4851"
  },
  {
    "caption": "A. Evaluation of siRNA-mediated depletion. U2OS cells were treated with control, Plk4 or hSAS-6 siRNA and immunoblotting was performed with the indicated antibodies. Asterisk indicates non-specific bands. The positions of molecular weight markers (kDa) are shown on the right.",
    "ncbi_link": "Plk4: 10733
SAS-6: 163786"
  },
  {
    "caption": "C, D, E. Quantification of the dispersion of satellite components upon depletion of Plk4 but not hSAS-6 knockdown. The results of PCM1 (C), hMsd1/SSX2IP (D) or BBS4 (E) are shown. Data represent the mean + SD (>200 cells, n=3). Statistical analysis was performed using two-tailed unpaired student's t-tests. **p<0.01, n.s. (not significant).",
    "ncbi_link": "Plk4: 10733
SAS-6: 163786"
  },
  {
    "caption": "F, G. U2OS cells were arrested in G1 and treated with control or Plk4 siRNA, followed by immunofluorescence microscopy by using indicated antibodies. Enlarged images (marked by arrowheads) are shown on the right. Quantification of PCM1 distribution is shown in G. >200 cells were counted and classified into two categories: normal (around and away from the centrosome) or dispersed. Data represent the mean + SD (n=3). Statistical analysis was performed using two-tailed unpaired student's t-tests. **p<0.01. Scale bar, 1 μm (F, right), 10 μm (F).",
    "ncbi_link": "Plk4: 10733"
  },
  {
    "caption": "H, I. siRNA-treated U2OS cells were transfected with empty vectors (EV) or plasmids containing Plk4 or siRNA-resistant Plk4-myc WT* or KD* and immunostained with the indicated antibodies. Cell peripheries are marked with solid lines, in which cells with yellow lines are successfully transfected (positive in myc signals), while those with white lines represent non-transfected cells. Quantification of PCM1 distribution is shown in I. Data represent the mean + SD (>200 cells, n=3). Statistical analysis was performed using two-tailed unpaired student's t-tests. ****p<0.0001, **p<0.01, n.s. (not significant). Scale bar, 5 μm (H).",
    "ncbi_link": "Plk4: 10733"
  },
  {
    "caption": "A, B. Either empty vector plasmids (EV) or those producing EGFP-PCM1 (A) or myc-Plk4 (B) were transfected into U2OS cells. Immunoprecipitation (IP) was performed with anti-GFP (A) or anti-myc antibodies (B), followed by immunoblotting with the indicated antibodies. DIC, the dynein intermediate chain.",
    "ncbi_link": "PCM1: 5108
Plk4: 10733"
  },
  {
    "caption": "C. Bacterially expressed and purified His-PCM1 (a.a. 1-1128) was incubated with MBP alone or MBP-Plk4 (WT or KD) in vitro, and pulled down by magnetic beads coupled with an anti-MBP antibody, followed by staining with Coomassie Blue (left) or immunoblotting with an anti-His antibody (right). Asterisks show non-specific bands. The mobility difference between Plk4-WT and Plk4-KD was reported previously [43, 48]. We reproducibly observed the upward mobility shift of His-PCM1 upon binding to MBP-Plk4-WT, but not Plk4-KD.",
    "ncbi_link": "Plk4: 10733"
  },
  {
    "caption": "E. Total cell extracts were prepared from U2OS cells treated with PCM1 siRNA and transfected with RNAi-resistant EGFP-PCM1-WT*. Cells were cultured asynchronously (As) or arrested in G1, G2 or M phase, followed by immunoprecipitation with an anti-GFP antibodies. Pulled down samples were immunoblotted with the indicated antibodies.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "A, B, C, D. siRNA-treated U2OS cells (PCM1 for A and B; Plk4 for C and D) were transfected with plasmids producing various EGFP-PCM1 constructs (WT*, S372A*, S372D* or S372E*), fixed and stained with the indicated antibodies (arrowheads point to the centrosome) (A and C). Quantification data are shown in B and D. >200 cells were counted and classified into three categories: normal (around and away from the centrosome), aggregated or dispersed. Data represent the mean + SD (n=3). Statistical analysis was performed using two-tailed unpaired student's t-tests. ***p<0.001, **p<0.01, *p<0.05, n.s. (not significant). Note that the percentage of cells displaying \"dispersed\" is analysed. Scale bars, 5 μm (A and C).",
    "ncbi_link": "PCM1: 5108
Plk4: 10733"
  },
  {
    "caption": "E. PCM1 siRNA-treated U2OS cells were transfected with two types of plasmids (EGFP- and mCherry-tagged) that produce PCM1-WT* and PCM1-S372A*. Immunoprecipitation and subsequent immunoblotting were performed with the indicated antibodies. Quantification data is shown on the right. Statistical analysis was performed using two-tailed unpaired student's t-tests. *p<0.05, **p<0.01, n.s. not significant.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "F. U2OS cells were treated with PCM1 siRNA and transfected with empty vectors (EV) or EGFP plasmids that produce PCM1-WT* or PCM1-S372A*. Immunoprecipitation was performed with an anti-GFP antibody, followed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "A. Immunofluorescence microscopy was performed using the indicated antibodies in hTERT-RPE-1 cells treated with control, PCM1 or Plk4 siRNA. Regions around the basal body (insets) are enlarged on the right hand side. Scale bars, 5 μm (left) and 1 μm (right).B. Quantification. At least 150 cells were counted (n=3). Statistical analysis was performed using two-tailed unpaired student's t-tests. ***p<0.001, ****p<0.0001.",
    "ncbi_link": "PCM1: 5108
Plk4: 10733"
  },
  {
    "caption": "C. hTERT-RPE-1 cells treated with PCM1 siRNA were transfected by an empty vector (EV) or plasmids producing PCM1-WT*, -S327A* or -S372E*, and immunofluorescence microscopy performed. Enlarged images of the regions around the basal body are shown in insets. Scale bars, 5 μm and 1 μm (inset).",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "B. Representative 2D projection of confocal  images showing caspase  activation at the dissection  time point  (red channel) and in the recent past (green channel, arrows) within putative escort somatic cells via DBS-S-QF  sensor; TUNEL staining  indicates apoptosis  (grey, arrowhead); DAPI  labels the nuclei  in the entire Figure. Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection. Genotype: Actin DBS-S-QF, UAS-mCD8-GFP, QUAS-tomato-HA/+; ;QUAS-Gal4  /+ (BL83123). C. Representative 2D projection of confocal  images showing escort  and follicular somatic cells permanently labelled with DBS-S-QF sensor (green channel, arrows); the arrowhead indicates the presence of  germline cells  positive for TUNEL staining  (red, arrowhead). Notice the lack of TUNEL  signal and therefore apoptosis  in somatic cells  permanently labelled with  DBS-S-QF sensor (green). Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection. Genotype: Actin DBS-S-QF, UAS-mCD8-GFP, QUAS-tomato-HA/+; QUAS-flippase  (BL30126)/+; Actin5C  FRT-stop-FRT lacZ-nls/+ (BL6355) Data information: Scale bars represents 10 µm in the entire Figure.",
    "ncbi_link": "Actin: 
Actin5C: 
flippase: 
GFP: 
HA: 
lacZ: 
tomato: 
CD8: 12525
Gal4: 855828"
  },
  {
    "caption": "D. Graph showing the percentage of germaria  permanently labelled  with DBS-S-QF overtime at 25 °C (N=4 biological replicates; n=520 and n=536 germaria  were inspected at 7 and 14 days post adult eclosion, respectively) and 29 °C (N=7, n=799 at 7 days and n=588 at 14 days). A two-way ANOVA and Tukey's multiple comparison tests were used to determine statistical significance (n.s = not significant; **** p<0.0001). Genotype: Actin DBS-S-QF, UAS-mCD8-GFP, QUAS-tomato-HA/+; QUAS-flippase  (BL30126)/+; Actin5C  FRT-stop-FRT lacZ-nls/+ (BL6355). Data information: The box plots show the median, first quartile, and third quartile of datasets. The whiskers illustrate the range between the maximum and minimum values of datasets.",
    "ncbi_link": "Actin: 
Actin5C: 
flippase: 
GFP: 
HA: 
lacZ: 
tomato: 
CD8: 12525"
  },
  {
    "caption": "A-B. Representative 2D projection of confocal  images showing the expression  of the cell identity Castor  in follicular cells  control with Dronc expression  (A: 109-30-Gal4  (BL7023)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/+) and without Dronc  (B: 109-30-Gal4  (BL7023)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/ UAS-flippase (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-QF). Notice the reduction in the number of Castor-expressing cells in the FCD  and the reduction in size of this region in B. Nuclei  are labelled with DAPI  (blue); Castor  (green) and FasIII  (grey) label the follicular cells; UAS-Histone-RFP  labels the nuclei  of Gal4-expressing cells (red). Data information: Scale bars represents 10 µm. Experimental flies  were kept after eclosion from the pupae for 14 days at 29°C prior to dissection (applicable to all panels).",
    "ncbi_link": "flippase: 
GFP: 
Histone: 
RFP: 
Dronc: 39173
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "C. Quantification of total number of follicular cells  (left) and Castor-expressing cells (right) within the FCD  (FasIII  positive region) in either heterozygous or homozygous Dronc  mutant conditions: Genotypes: CTRL= 109-30-Gal4  (BL7023)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/+; Dronc -/- = 109-30-Gal4  (BL7023)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/ UAS-flippase  (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-QF.CTRL=ptc-Gal4  (BL2017)/+; UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/+. Dronc  -/- = ptc-Gal4  (BL2017)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/ UAS-flippase  (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-QF. N=2; the n number for each column in order of appearance n=16, n=14, n=20, n=17, n=19, n=18. Statistical significance was determined by using an unpaired parametric Welch's t-test (****p≤0.001). The median and quartiles are indicated in the violin plots. Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels).",
    "ncbi_link": "flippase: 
GFP: 
Histone: 
RFP: 
Dronc: 39173
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "E. Percentage of germaria  showing TUNEL staining  in different cell types of the germarium  (somatic cells  and germline cells) upon altering Dronc  expression in all of the  escort cells  and follicular stem cells. N=3 biological replicates; the n number of inspected germaria  per condition is indicated close to the genotype. The genotypes in the graph are: White triangle (n=378 germaria) = ptc-Gal4  (BL2017)/+; +/+. Yellow circle (n=381) = ptc-Gal4  (BL2017)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/ +. Red square (n=196) = ptc-Gal4  (BL2017)/+; DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/ UAS-flippase  (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-suntag-HA. Blue circle (n=184)= ptc-Gal4  (BL2017)/UAS-Dronc  (BL56198); DroncKO UAS-Histone-RFP  (BL56555) Tub-G80ts (BL7019)/+. An ordinary one-way ANOVA and Holm-Sidak's multiple comparison test was used to determine statistical significance (n.s = not significant; ** p≤0.01; *** p≤0.001; ****p≤0.0001). The graph shows the mean and standard deviations. Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels).",
    "ncbi_link": "flippase: 
GFP: 
HA: 
Histone: 
RFP: 
suntag: 
Dronc: 39173
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "A. Quantification of total number of follicular cells in germaria  with  follicular stem cells expressing normal levels of Dronc  (DroncKO/+), without Dronc  expression (DroncKO/DroncKO- Suntag-HA-Cherry), and expressing a catalytically inactive form of Dronc  (DroncKO/DroncKO- FL-CAEA-Suntag-HA-Cherry ). The genotypes are as follows: 109-30-Gal4  (BL7023)/+ (n=13). 109-30-Gal4  (BL7023)/+; DroncKO Tub-G80ts (BL7019) / UAS-flippase  (BL8209) DroncKO-FRT  Dronc-GFP-Apex  FRT-Suntag-HA-Cherry    (n=15). 109-30-Gal4  (BL7023)/+;  DroncKO Tub-G80ts (BL7019) / UAS-flippase  (BL8209) DroncKO-FRT Dronc-GFP-Apex  FRT-Dronc  FL-CAEA-Suntag-HA-Cherry  (n=14). A one-way ANOVA and Dunnett's multiple comparison post-test was used to determine statistical significance (***p≤0.001; ****p≤0.0001). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). All the experimental data shown have been obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of germline cells wrapped by follicular cells.",
    "ncbi_link": "Cherry: 
flippase: 
GFP: 
HA: 
Suntag: 
Dronc: 39173
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "D. Quantification of total number of  follicular cells  within the FasIII  cellular domain in the following genotypes: 109-30-Gal4/+; Tub-G80ts (BL7019)/+ (n=16). 109-30-Gal4  (BL7023)/UAS-DriceRNAi UAS-DecayRNAi (a gift from Pascal Meier); UAS-DammRNAi, UAS-Dcp1RNAi (a gift from Pascal Meier) (n=15). 109-30-Gal4  (BL7023)/+; Tub-G80ts (BL7019)/ UAS-Dcp1RNAi (BL28909) (n=25) 109-30-Gal4  (BL7023)/+; Tub-G80ts (BL7019)/ UAS-DriceRNAi (BL32403) (n=16) 109-30-Gal4  (BL7023)/UAS-Dark-sh; Tub-G80ts (BL7019)/+ (a gift from M. Miura) (n=18). 109-30-Gal4  (BL7023)/UAS-microRNA-RHG; Tub-G80ts (BL7019)/+ (a gift from Iswar Hariharan) (n=10). A one-way ANOVA and Dunnett's multiple comparison post-test was used to determine statistical significance (***p≤0.001; ****p≤0.0001). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). All the experimental data shown have been obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria containing one single group of  germline cells wrapped by follicular cells.",
    "ncbi_link": "Damm: 36266
Dark: 36914
Dcp1: 37790
Decay: 42008
Drice: 43514
Gal4: 855828
RHG: 37038
Tub: 40554"
  },
  {
    "caption": "A-B. Representative 2D projections of confocal  images showing the expression  of  Ci-155 (blue and grey channels), ptc-GFP  (green and grey; ptc-GFP  is a bona-fide transcriptional read out of Hh-pathway and weak hypomorph allele and Castor  (red and grey) in germaria  with either normal (A) or deficient Dronc expression  (B). Genotypes: 109-30-Gal4  (BL7023)/ptc-GFPCB02030 (a gift from Isabel Guerrero) (A) and 109-30-Gal4  (BL7023)/ptc-GFPCB02030; DroncKOTub-G80ts (BL7019)/ UAS-flippase DroncKO-FRT-Dronc-GFP-APEX-FRT-QF. Data information: Scale bars represents 10 µm in the entire figure. Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels).",
    "ncbi_link": "flippase: 
GFP: 
Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "D. Western blot showing  Caspase-9 expression (upper lane) and actin  (bottom lane, loading control) in either control or Caspase-9 deficient  OVCAR-3 cells (24h and 72h post-transfection of an shRNA against Caspase-9). Notice the strong downregulation of Caspase-9 72h after siRNA treatment.",
    "ncbi_link": "Caspase-9: 842"
  },
  {
    "caption": "H. Quantification of total number of follicular cells (left) or Castor-expressing cells (right) within the FasIII  cellular domain in the following genotypes from left to right: Dronc  -/- = CTRL= 109-30-Gal4  (BL7023)/; DroncKOTub-G80ts (BL7019)/ UAS-flippase  (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-QF (n=16). CTRL= 109-30-Gal4  (BL7023)/UAS-smoAct  (BL44621); DroncKOTub-G80ts (BL7019)/+ (n=11). Dronc  -/- = 109-30-Gal4  (BL7023)/UAS-smoAct (BL44621); DroncKOTub-G80ts (BL7019)/ UAS-flippase  (BL8209) DroncKO-FRT-Dronc-GFP-APEX-FRT-QF (n=8). CTRL= 109-30-Gal4  (BL7023)/UAS-Ci  (BL28984); DroncKOTub-G80ts (BL7019)/+. (n=7). Dronc  -/- = 109-30-Gal4  (BL7023)/UAS- UAS-Ci (BL28984); DroncKOTub-G80ts (BL7019)/ UAS-flippase  (BL8209)  DroncKO-FRT-Dronc-GFP-APEX-FRT-QF (n=21). A Kruskal-Wallis test and Dunn's multiple comparison post-test were used to determine statistical significance (n.s.= not significant; ****p≤0.0001;). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). Unless otherwise indicated, all experimental data presented were obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of  germline cells wrapped by follicular cells.",
    "ncbi_link": "flippase: 
GFP: 
Ci: 43767
Dronc: 39173
Gal4: 855828
smo: 33196
Tub: 40554"
  },
  {
    "caption": "J. Quantification of total number of follicular cells (left) or Castor-expressing cells (right) within the FasIII  cellular domain in the following genotypes from left to right: Dronc  +/+ = ptc-Gal4  (BL2017)/+; Tub-G80ts (BL7019) (n=19). Dronc  +/- = ptc-Gal4  (BL2017)/+; DroncKOTub-G80ts (BL7019)/+ (n=23). Dronc  +/- UAS-Dronc  = ptc-Gal4  (BL2017)/+; DroncKOTub-G80ts (BL7019)/UAS-Dronc  (BL56198) (n=14). A one-way ordinary ANOVA and Welch's correction were used to establish statistical significance (n.s.= not significant; ****p≤0.0001). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). Unless otherwise indicated, all experimental data presented were obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of germline cells wrapped by follicular cells.",
    "ncbi_link": "Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "B. Relative number of Ptc-positive puncta per germaria  of the following genotypes, from left to right: DroncKO Tub-G80ts /+ (n=10). ptc-Gal4  /+; Tub-G80ts/+ (n=9). ptc-Gal4  /+; DroncKO Tub-G80ts /+ (n=10). A Kruskal-Wallis test and Dunn's multiple comparison post-test were used to determine statistical significance (***p≤0.001 Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). All the experimental data shown have been obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of germline cells wrapped by follicular cells.",
    "ncbi_link": "Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "C. Western blot  showing Ptc  (upper lane) and actin  (bottom lane, loading control) expression in ovaries  of the genotypes shown in A. Notice the Ptc  accumulation in double heterozygous germaria (ptc-Gal4  /+; DroncKO Tub-G80ts /+).",
    "ncbi_link": "Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "E. Pearson colocalization  index between Ptc  and Atg8  in germaria  of the following genotypes: ptc-Gal4  (BL2017)/ UAS-GFP-mCherry-Atg8  (BL37749) (n=12). ptc-Gal4  (BL2017)/UAS-GFP-mCherry-Atg8  (BL37749); DroncKOTub-G80ts (BL7019)/+ (n=18). An unpaired parametric Welch's t-test was used to establish the statistical significance (** p≤0.01). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). All the experimental data shown have been obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of germline cells wrapped by follicular cells.",
    "ncbi_link": "Atg8: 
GFP: 
mCherry: 
Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "B. Total number of Atg8+ autophagosomes  in germaria  of the following genotypes ptc-Gal4  (BL2017)/ UAS-GFP-mCherry-Atg8  (BL37749) (n=21). ptc-Gal4  (BL2017)/ UAS-GFP-mCherry-Atg8  (BL37749); DroncKOTub-G80ts (BL7019)/+ (n=28). An unpaired parametric Welch's t-test was used to establish the statistical significance (* p≤0.05). Data information: Experimental flies  were kept after eclosion from the pupae  for 14 days at 29°C prior to dissection (applicable to all panels). All the experimental data shown have been obtained from N ≥ 2 biological replicates. The median and quartiles are indicated in the violin plots. All the quantifications were made in germaria  containing one single group of germline cells wrapped by follicular cells.",
    "ncbi_link": "Atg8: 
GFP: 
mCherry: 
Dronc: 39173
Gal4: 855828
ptc: 35851
Tub: 40554"
  },
  {
    "caption": "H. Western blot showing the expression levels of the autophagy marker p62  (upper lane), Caspase-9 (middle lane) and Actin  (bottom lane, loading control) in either scrambled or Caspase-9  deficient  OVCAR-3 cells; the protein levels of the different read outs were measured at 72h after siRNA treatment in cells grown during the last 4 h before sample processing in our standard cell culture conditions, in cell culture media containing EtOH  (0.2%), and in cell culture media containing EtOH  (0.2%) +  bafilomycin A1  (400nM).",
    "ncbi_link": "Caspase-9: 842"
  },
  {
    "caption": "E. Liposomes were treated with Dln1M5 or Dln1 of different concentrations at a fixed pH value of 5.5.",
    "ncbi_link": "Dln1: 503710"
  },
  {
    "caption": "C&D. Transmission electron microscope micrograph of dispersed ring-like structures of Dln1M5 or Dln1D135A oligomers on lipid monolayer. The inset represents a few 2D class averages showing the octamer pattern from some individual rings.",
    "ncbi_link": "Dln1: 503710"
  },
  {
    "caption": "C&D. Transmission electron microscope micrograph of dispersed ring-like structures of Dln1M5 or Dln1D135A oligomers on lipid monolayer. The inset represents a few 2D class averages showing the octamer pattern from some individual rings.",
    "ncbi_link": "Dln1: 503710"
  },
  {
    "caption": "(A-D) Primary cultures from D. melanogaster embryos expressing GFP-Atg8a under the control of Dmef2-Gal4, stained with Phalloidin (actin) in red. Inset are magnifications of areas denoted by dotted line. (A) In untreated control cultures, GFP-Atg8a localizes throughout the muscle cytoplasm and nuclei. (B) Addition of rapamycin (Rap) for 12 hrs results in the formation of small GFP-Atg8a labeled punctae. (C) Addition of chloroquine (CQ) for 12 hrs results in the accumulation of large GFP-Atg8a labeled vesicles that localize around the nucleus and between the myofibers. (D) Addition of both CQ and Rap for 12hrs, triggers the formation of greater numbers of enlarged vesicles in the muscles than either drug alone. (E) Knockdown of the core autophagy gene, Atg1, prevents the formation of GFP-Atg8a vesicles in CQ+Rap treated cultures. (F) Quantification of the mean ratio of GFP-Atg8a punctae area to total muscle area per well (n = 4). Error bars indicate SEM with **p<.01; ***p<.001.",
    "ncbi_link": "Gal4: 
Atg1: 39454
Dmef2: 36032"
  },
  {
    "caption": "(A-D) Primary cultures from D. melanogaster embryos expressing GFP-Atg8a under the control of Dmef2-Gal4, stained with Phalloidin (actin) in red. Inset are magnifications of areas denoted by dotted line. (A) In untreated control cultures, GFP-Atg8a localizes throughout the musclecytoplasm and nuclei. (B) Addition of rapamycin (Rap) for 12 hrs results in the formation of small GFP-Atg8a labeled punctae. (C) Addition of chloroquine (CQ) for 12 hrs results in the accumulation of large GFP-Atg8a labeled vesicles that localize around the nucleus and between the myofibers. (D) Addition of both CQ and Rap for 12hrs, triggers the formation of greater numbers of enlarged vesicles in the musclesthan either drug alone. (E) Knockdown of the core autophagy gene, Atg1, prevents the formation of GFP-Atg8a vesicles in CQ+Rap treated cultures. (F) Quantification of the mean ratio of GFP-Atg8a punctae area to total muscle area per well (n = 4). Error bars indicate SEM with **p<.01; ***p<.001.",
    "ncbi_link": "Gal4: 
Atg1: 39454
Dmef2: 36032"
  },
  {
    "caption": "(E) Control white RNAi muscles starved and treated with CQ accumulate GFP-Atg8a punctae, but very few colocalize with ubiquitin (Ubi). (F) Knockdown of Rpn1 in starved + CQ muscle strongly inhibits the formation of GFP-Atg8a punctae. The remainder colocalize with ubiquitin. (G) Quantification of the mean GFP-Atg8a punctae area and Mander's overlap coefficient for GFP-Atg8a and Ubi for genotypes shown in E and F. Error bars indicate SEM for n = 8 ventral longitudinal muscles from individual animals, with p-values for Rpn1 RNAi relative to white RNAi control (***p<.001).",
    "ncbi_link": "Rpn1: 40174
white: 31271"
  },
  {
    "caption": "(H, I) Autophagosome number is reduced, but autophagic flux is not significantly altered in starved Rpn1 vs. white RNAi muscles expressing GFP-mCherry-Atg8. (J) Flux measurement is shown on the right as the ratio of mCherry punctae to GFP-mCherry (n = 6). SEM is indicated.",
    "ncbi_link": "Rpn1: 40174
white: 31271"
  },
  {
    "caption": "(K) Anti-Atg8a Western blot of third instar muscle lysate from Dmef2-Gal4; UAS-RNAi animals. In fed white RNAi control, endogenous Atg8a appears as a single band (Atg8a-I). 6 hrs starvation induces lipid modification of Atg8a and the appearance of a second band (Atg8a-II). Knockdown of Atg1 or Rpn1 inhibits Atg8a modification, indicating reduced autophagy levels.",
    "ncbi_link": "Gal4: 
Atg1: 39454
Dmef2: 36032
Rpn1: 40174
white: 31271"
  },
  {
    "caption": "(A-D) Inhibition of the proteasome by overexpression of a temperature sensitive proteasome mutant (DTS). Dmef2-Gal4, UAS-GFP-Atg8a control and UAS-DTS; Dmef2-Gal4, UAS-GFP-Atg8a and animals were shifted to the restrictive temperature then starved and CQ treated 6 hrs prior to dissection. 18 hrs post-shift (PS), both control (A) and DTS muscles (B) accumulate GFP-Atg8a punctae, but the latter also accumulate ubiquitin (Ubi) aggregates. 48 hrs PS, control muscles (C) maintain strong autophagy induction, but DTS mutant muscles (D) have reduced GFP-Atg8a punctae accumulation, similar to the Rpn1 knockdown phenotype. (E) Quantification of the mean GFP-Atg8a punctae and Mander's overlap coefficient for GFP-Atg8a and Ubi for genotypes shown in A-D (SEM is indicated for n = 8 ventral longitudinal muscles from individual animals with p-values of DTS relative to control). Dark green = Dmef2-Gal4, UAS-GFP-Atg8a; Light green = UAS-DTS; Dmef2-Gal4, UAS-GFP-Atg8a.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(F) Western blot analysis of endogenous Atg8a from third instar muscle lysate. 6 hrs starvation induces lipidated Atg8a-II in Dmef2-Gal4 control at both 18 hrs and 48 hrs PS, but not in DTS at 48 hrs PS.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(A-C) Time course of effect of temperature shift on aggregates, autophagosomes, and larval locomotion in UAS-DTS; Dmef2-Gal4, UAS-GFP-Atg8a animals starved 6 hrs prior to analysis. (A) The number of ubiquitin aggregates peaks at 18-24 hrs PS, and decreases significantly from 18 to 48 hrs PS (n = 10 and p-values shown relative to 18 hrs PS). (B) The number of GFP-Atg8a punctae peaks at 12-24 hrs PS and decreases significantly from 18 to 48 hrs PS (n = 10 and p-values shown relative to 18 hrs PS). (C) Larval locomotion, measured as the time to crawl 3cm, gradually and significantly worsens from 18 to 48 hrs PS (n = 6 and p-values shown relative to 0 hrs PS.",
    "ncbi_link": "Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(D-E) tyramine (Tyr) treatment reduces GFP-Atg8a punctae in larval muscle. UAS-DTS; Dmef2-Gal4, UAS-GFP-Atg8a animals were placed on 100mg/ml Tyr (D) or control food (E), shifted to restrictive temperature for 18hrs, and starved 6 hrs prior to dissection.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(F-H) Effect of Tyr treatment on aggregates, autophagosomes, and larval locomotion in UAS-DTS; Dmef2-Gal4, UAS-GFP-Atg8a and Dmef2-Gal4, UAS-GFP-Atg8a animals, shifted to restrictive temperature for 18hrs, and starved 6 hrs prior to dissection. Aggregate (F) and GFP-Atg8a punctae (G) numbers in muscles are significantly reduced with 100 mg/ml Tyr treatment in DTS but not control animals 18 hrs post-shift (PS). (H) 100 mg/ml Tyr treatment significantly worsens larval locomotion in both control and DTS animals 18 hrs PS. n = 12 and p-values shown relative to non-Tyr treated animals. For all measurements, SEM is shown with *p<.05; **p<.01; ***p<.001.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(I) Western blot analysis of endogenous Atg8a from third instar muscle lysate 18 hrs PS. 6 hrs starvation induces lipidated Atg8a-II in Dmef2-G4 control with or without 100 mg/ml Tyr. After 6hrs starvation, Atg8a-II levels are reduced in DTS + 100 mg/ml Tyr relative to untreated DTS.",
    "ncbi_link": "Dmef2: 36032
DTS: 39855"
  },
  {
    "caption": "(D-H)Dmef2-Gal4 drives expression of UAS-GFP-Atg8a in animals starved on low nutrient food for 6 hrs + 2.5 mg/ml CQ for 6 hrs. RNAi knockdown of CG41099 (E), CG7112 (F), CG31935 (G), and Rab3-GAP (H), blocks the formation of GFP-Atg8a labeled autophagosomes compared to knockdown of white (D).",
    "ncbi_link": "Gal4: 
CG31935: 33338
CG41099: 3355072
CG7112: 38945
Dmef2: 36032
Rab3-GAP: 34626
white: 31271"
  },
  {
    "caption": "(I-M) Dmef2-Gal4 drives expression of UAS-myc-Atg8a in animals starved on low nutrient food for 6 hrs + 2.5 mg/ml CQ for 6 hrs. The effect of the RAB3GAPs is not via Rab3 or Rab5 function, as a Rab3 null mutation (J), expression of a constitutive active form of Rab3 (Q80L) (K) or Rab5 (Q88L) (L) has no effect on muscle autophagy compared to control (I). Expression of a constitutive active form of Rab39 (Q69L) (M) reduces myc-Atg8a labeled vesicles. (N) Quantification of autophagy phenotypes from panels D-M. SEM is indicated, with n = 8 ventral longitudinal muscles from individual animals and **p<.01; ***p<.001.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
Rab3: 36127
RAB3GAP: 34626
Rab39: 31684
Rab5: 33418"
  },
  {
    "caption": "(O) Atg8a and Rab3-GAP colocalize to autophagosomes. Dmef2-Gal4 drives expression of UAS-myc-Atg8a and UAS-CFP-Rab3-GAP in animals starved and treated with CQ for 6 hrs. In all panels green = GFP-Atg8a and red = myc-Atg8a, and blue = CFP-Rab3Gap2.",
    "ncbi_link": "Gal4: 
Dmef2: 36032
Rab3-GAP: 34626"
  },
  {
    "caption": "(P) Anti-Atg8a Western blot of third instar muscle lysate from Dmef2-Gal4 driving the RNAi or overexpression constructs shown in D-N. Total levels of endogenous Atg8a are variable, but only knockdown of CG41099, CG7112, CG31935, Rab3-GAP, or overexpression of Rab39 (Q69L) block induction of lipidated Atg8a-II following 6 hrs starvation.",
    "ncbi_link": "Gal4: 
CG31935: 33338
CG41099: 3355072
CG7112: 38945
Dmef2: 36032
Rab3-GAP: 34626
Rab39: 31684"
  },
  {
    "caption": "(A) Primary cultured muscles with control lacZ RNAi, treated for 12 hrs with Rap+CQ. Note the formation of large GFP-Atg8a vesicles throughout the muscles. (B) GFP-Atg8a vesicles are reduced in primary cultured muscles with GlyS RNAi, treated for 12 hrs with Rap+CQ. Knockdown of Pfk (C) or CG9485 (D) causes increased accumulation of GFP-Atg8a vesicles in primary cultured muscles treated for 12 hrs with Rap+CQ. (E) Quantification for A-D of the mean ratio of GFP-Atg8a punctae area to total muscle area per well (n = 4). SEM is indicated with *p<.05; **p<.01.",
    "ncbi_link": "CG9485: 37435
GlyS: 41823
Pfk: 36060"
  },
  {
    "caption": "(F) Control white RNAi muscles accumulate large autophagosomes at 1 mg/ml CQ. (G) RNAi knockdown of CG9485 increases autophagosome accumulation in the muscle. (H) RNAi knockdown of AGBE reduces autophagic vesicle accumulation in the muscle. (I) Quantification of the GFP-Atg8a punctae area in muscles from white, CG9485, and AGBE knockdowns.n = 6 larval muscles with SEM indicated and *p<.05.",
    "ncbi_link": "AGBE: 326264
CG9485: 37435
white: 31271"
  },
  {
    "caption": "(J) Western blot analysis of endogenous Atg8a from third instar muscle lysate. Dmef2-Gal4 driven knockdown of AGBE but not CG9485 inhibits Atg8a lipidation, indicating reduced autophagy levels.",
    "ncbi_link": "Gal4: 
AGBE: 326264
CG9485: 37435
Dmef2: 36032"
  },
  {
    "caption": "RFP+ (G1 phase), GFP+ (G2 phase), and GFP+/RFP+ (S phase)   RPE-FUCCI cells were sorted by flow cytometry, RNA was extracted and analyzed using qRT-PCR (n=3). Expression is normalized to GAPDH  mRNA. Bars show mean ± SD.",
    "ncbi_link": "GFP: 
RFP: 
GAPDH: 2597"
  },
  {
    "caption": "RPE cells transfected with control or FAM110A siRNA were fixed with 4 % PFA, probed with  rabbit polyclonal antibody against  FAM110A and mouse monoclonal to  γ-tubulin, and were analyzed by confocal microscopy. Shown is maximal projection of representative mitotic (upper panel) and interphase (lower panel) cells. Scale bars indicate 10 μm.",
    "ncbi_link": "FAM110A: 83541"
  },
  {
    "caption": "Quantification of the  mitotic index in three experiments from (A) and in  RPE cells transfected with siRNAs to FAM110B and CSPP1 that were analyzed in parallel. Shown is median ±SD (n=3). Statistical significance was determined by ANOVA (* p<0.05, ** p<0.005).",
    "ncbi_link": "CSPP1: 79848
FAM110B: 90362"
  },
  {
    "caption": "RPE  cells transfected with control or FAM110A  siRNA were grown for 48 h and treated with MG132 30 min prior fixation to trap mitotic cells in metaphase. Impaired  chromosomal alignment and multipolar spindles were scored and representative  images are shown. Scale bars indicate 20 μm, arrowheads point to misaligned chromosomes. More than 30  metaphases were evaluated per condition (n=3). Bars indicate median ±SD. Statistical significance was determined by two-tailed t-test, (*** p<0.001, * p<0.05).   Quantification of lagging chromosomes  in anaphase  cells from (E). More than 30 anaphases were evaluated per condition (n=3). Representative images of abnormal anaphase are shown, scale bars indicate 20 μm, arrowheads point to incorrectly segregating chromosomes. Statistical significance was determined by two-tailed t-test. Bars indicate median ±SD (*** p<0.001).   ",
    "ncbi_link": "FAM110A: 83541"
  },
  {
    "caption": "Cell extracts from asynchronously growing or mitotic  RPE-EGFP or RPE-EGFP-FAM110A cells were incubated with  GFP Trap  and bound proteins were analyzed by immunoblotting. Antibody against pS10H3 was used as a marker of mitosis.",
    "ncbi_link": "EGFP: 
FAM110A: 83541"
  },
  {
    "caption": "RPE cells or RPE cells stably expressing indicated EGFP-FAM110A variants were transfected with control (siNC), FAM110A  or CSNK1D siRNA and grown for 48 h. Alternatively, cells were incubated with PF670462  for the last 12 h. Cells were treated with MG132 for 30 min prior fixation. Impaired chromosomal alignment was scored in >30 metaphase cells per condition. Error bars indicate median ±SD. Statistical significance was determined by ANOVA (n=3) (**** p<0.0001, *** p<0.001).",
    "ncbi_link": "EGFP: 
CSNK1D: 1453
FAM110A: 83541"
  },
  {
    "caption": "Representative immunoblot analysis of samples from (D). Full arrow indicates migration of the EGFP-FAM110A-WT, empty arrow of endogenous FAM110A.",
    "ncbi_link": "EGFP: 
FAM110A: 83541"
  },
  {
    "caption": "RPE1 were transfected with control siRNA or CSNK1D  siRNA or were treated with PF670462  prior fixation. Cells were probed with rabbit polyclonal to FAM110A  and mouse monoclonal to γ-Tubulin. Representative  images are shown, scale bars indicate 10 μm.   Quantification of (A). Plotted is median FAM110A intensity at  spindle poles positive for  γ-tubulin ± SD. Each dot represents a single  spindle pole. Statistical significance was determined by ANOVA (n=3) (**** p<0.0001).   ",
    "ncbi_link": "CSNK1D: 1453"
  },
  {
    "caption": "Cells expressing the wild-type or mutant EGFP-FAM110A were fixed and stained for γ-tubulin and α-tubulin and analyzed by  confocal microscopy (z-stack 0.16 µm). Representative images of maximal projections of the metaphase cells are shown, scale bars indicate 10 μm. Merged images show signal of DAPI,  γ-tubulin and  EGFP. Insets show a single Z plane at the spindle pole.",
    "ncbi_link": "EGFP: 
FAM110A: 83541"
  },
  {
    "caption": "A, RT-qPCR (n = 3-12 biological replicates) analyses of CGN  expression in different mouse  organs at P21.",
    "ncbi_link": "CGN: 70737"
  },
  {
    "caption": "B. MDCK  cells expressing WT or mutant CGN  were immunolabeled  with CGN  or Flag  antibodies.",
    "ncbi_link": "CGN: 57530"
  },
  {
    "caption": "D. RT-qPCR  of CGN  expression in transfected MDCK  cells (n = 3 biological replicates). Data information: Data are presented as mean ± SEM; unpaired Student's t-test was used in (D). ns, not significant, P > 0.05.",
    "ncbi_link": "CGN: 57530"
  },
  {
    "caption": "A-C. DPOAE  thresholds (A), ABR  thresholds (B) and ABR  P1 amplitudes  (C) of the 2-month old control (Cgnfl/fl) and Cgn-cKO (Cgnfl/fl;Pou4f3creER/+) mice. Control mice  (circle), n = 16 mice  (female  = 8, male  = 8); Cgn-cKO mice  (square), n = 19 mice  (female  = 11, male  = 8). Data information: Data are presented as mean ± SEM; two-way ANOVA was used * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001.",
    "ncbi_link": "Cgn: 70737
cre: 2777477
ER: 13983
Pou4f3: 18998"
  },
  {
    "caption": "D-I. Growth curves of ABR  P1 amplitudes  at different cochlear  frequencies (5.6 - 32 kHz) of the 2-month old control and Cgn-cKO mice. Control mice  (circle), n = 16 mice  (female  = 8, male  = 8); Cgn-cKO mice  (square), n = 19 mice  (female  = 11, male  = 8). Data information: Data are presented as mean ± SEM; two-way ANOVA was used * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001.",
    "ncbi_link": "Cgn: 70737"
  },
  {
    "caption": "J. Whole mount immunofluorescence    of the organ of Corti   from 2-month old control and Cgn-cKO mice. Phalloidin  (F-actin, magenta); Myosin7a  (hair cells, green). White arrows label the lost OHCs.",
    "ncbi_link": "Cgn: 70737"
  },
  {
    "caption": "C. Whole mount immunofluorescence  of CGN expression  in organ of Corti   from P21 CgndelG mouse.",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "D-I. DPOAE  thresholds (D, E), ABR  thresholds (F, G), and ABR P1 amplitudes at 32 kHz (H, I) of 2-month old (D, F, H) or 6-month old (E, G, I)  CgndelG mice. Control Cgn+/+ mice  (circle), n = 3 mice  (2-month, female  = 1, male  = 2) or 15 mice  (6-month, female  = 4, male  = 11); CgndelG/+ mice  (triangle), n = 8 mice  (2-month, female  = 4, male  = 4) or 20 mice  (6-month, female  = 9, male = 11); CgndelG/delG mice  (square), n = 7 mice  (2-month, female  = 4, male  = 3) or 16 mice  (6-month, female  = 6, male  = 10). Cgn+/+ vs CgndelG/delG, * (red); Cgn+/+ vs CgndelG/+, * (green). Data information: Data are presented as mean ± SEM; two-way ANOVA was used * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001.",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "J. Whole mount immunofluorescence  of the organ of Corti  from 7-month old CgndelG mice. White arrows indicate lost OHCs  by F-actin  labeling (Phalloidin).",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "K. Percentage of OHC  loss in 7-month old CgndelG mice  (n = 3-8 biological replicates from 3 cochleae). Data information: Data are presented as mean ± SEM; two-way ANOVA was used * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001.",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "F. Percentage of OHC  loss in noise exposed CgndelG mice  (n = 5-9 cochleae). Data information: Data are presented as mean ± SEM; one-way ANOVA was used in (F). ** P < 0.01, *** P < 0.001 and **** P < 0.0001.",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "Whole mount immunofluorescence   with LMO7  antibody on 2-month old CgndelG mice  at 32 kHz cochlear  region",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "Whole mount immunofluorescence  with Spectrin β II  antibody on 2-month old CgndelG mice  at 32 kHz cochlear  region",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "A. Low-magnification SEM  images of hair bundles   from 2-month old Cgn+/+ and CgndelG/delG mice. B. High-magnification SEM  images of IHC hair bundles  from 2-month old Cgn+/+ and CgndelG/delG mice. C. High-magnification SEM  images of OHC hair bundles   from 2-month old Cgn+/+ and CgndelG/delG mice. Shown are hair bundles of the second-row OHCs  (OHC2).",
    "ncbi_link": "Cgn: 57530"
  },
  {
    "caption": "(B) Total lysates from  HEK293T transfected with Flag-OFD1  were  IP with anti-myosin VI antibodies (1295 and 1296) and an unrelated rabbit antibody (anti-GST, as control). IB was performed with anti-Flag and anti-myosin VI  antibodies. (C) Total lysates from  HEK293T transfected with Flag-OFD1 or Flag (as control) were  IP with anti-Flag antibody-conjugated beads. IB  was performed with anti-Flag and anti-myosin VI  antibodies.",
    "ncbi_link": "Flag: 
OFD1: 8481"
  },
  {
    "caption": "(D) Selected sections deriving from  TEM  analysis of A549 wild-type versus myosin VI  KO cells. The cells were immunogold-labelled with anti-myosin VI antibody. The centrioles in the images are indicated with white dashed circles. Scale bar, 200 nm. Top: representation of the estimated  localisation of myosin VI at the  centrioles.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(F)  GST pulldown assay using myosin VI tail (835-1295) construct (or GST alone as control) and lysates from HEK293T cells transfected with the indicated Flag-OFD1 constructs (or Flag alone, as control). IB was performed with anti-Flag antibody. Ponceau staining  as indicated.",
    "ncbi_link": "Flag: 
OFD1: 8481"
  },
  {
    "caption": "D) Quantification of OFD1 intensity at the mother  or  daughter   centrioles. Results are expressed as fold change with respect to mock average intensity. Bars represent mean ± SD. Mother centrioles: Mock, n=148 cells; MyoVI KD, n=199 cells, from four independent experiments.  Daughter centrioles: Mock, n=101 cells; MyoVI  KD, n=148 cells, from three independent experiments. **** P<0,0001 by Mann-Whitney test.",
    "ncbi_link": "MyoVI: 4646"
  },
  {
    "caption": "(F-G)  IF analysis of Cep164 signal. hTERT-RPE1 cells were transfected with siRNA against myosin VI and/or OFD1. Four days after transfection, cells were treated with nocodazole (1 hour, 6 μg/ml) and immunostained with anti-OFD1, anti-centrin1 and anti-Cep164  antibodies. (F) Representative images. Scale bar, 1 μm. (G) Quantification of Cep164 intensity at the  mother   centrioles. Results are expressed as fold change with respect to mock average intensity. Bars represent mean ±SD. Mock, n=147 cells; OFD1 KD, n=146 cells; MyoVI  KD, n=150 cells;  MyoVI + OFD1 KD, n=151 cells, from four independent experiments. ** P<0,005; **** P<0,0001 by Kruskal-Wallis test.",
    "ncbi_link": "myosin VI: 4646
MyoVI: 4646
OFD1: 8481"
  },
  {
    "caption": "(A)  Growth  curve of hTERT-RPE1 cells transfected with myosin VI  siRNA. A representative plot of three independent experiments is shown. (B)  Growth curve of BJ-hTERT  cells transfected with myosin VI  siRNA. A representative plot of two independent experiments is shown.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(G) Representative bright field  images of cells treated with the indicated  p53 and  myosin VI siRNAs. Scale bar, 200 μm.",
    "ncbi_link": "myosin VI: 4646
p53: 7157"
  },
  {
    "caption": "(A)  Super-resolution  analysis  of OFD1 localisation at the  centrioles. hTERT-RPE1 cells were transfected with siRNA against  myosin VI, immunostained with anti-OFD1 and anti-acetylated tubulin antibodies and visualised using structured illumination microscopy (SIM). Representative images are shown, scale bar, 500 nm. A scheme of the estimated  localisation of OFD1 in the two conditions is depicted on the right side.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "(C)  dSTORM super-resolution analysis of the distal appendage markers  FBF1 and  ODF2 in control and  myosin VI-depleted cells. To emphasise the symmetry of the structures, the signals from all nine   appendages   were averaged (bottom). Representative images are shown; scale bar, 200 nm.",
    "ncbi_link": "myosin VI: 4646"
  },
  {
    "caption": "FRAP  analysis of centriole-associated  GFP-OFD1.  hTERT-RPE  cells stably expressing GFP-OFD1 and centrin1-dTomato were transfected with siRNA against  myosin VI. After four days, cells were treated with nocodazole (1 hour, 6 μg/ml) and subjected to live-cell imaging. (E) A representative graph of one out of three experiments. For each  time point, the fraction of recovery of GFP-OFD1 is shown. Results are expressed as means with 95% confidence interval. n=12 cells (Mock), n=13 cells (MyoVI KD). (F) Quantification of the half-time  of fluorescence recovery (t1/2,) and of the mobile fraction of GFP-OFD1. Results are expressed as mean ±SD. n=41 cells (Mock), n=31 cells (MyoVI  KD), from three independent experiments. ns, not significant; *** P<0,0005 by Unpaired T-test.",
    "ncbi_link": "dTomato: 
GFP: 
centrin1: 1068
myosin VI: 4646
MyoVI: 4646
OFD1: 8481"
  },
  {
    "caption": "(B)  IF analysis of PCM1 signal. hTERT-RPE1  cells were transfected with siRNA against  myosin VI  and immunostained  with anti-PCM1 and anti-Cep135 antibodies. Upper panel, representative images, scale bar, 2 μm. Lower panel, quantification of PCM1  intensity. Results are expressed as fold change with respect to mock average intensity. Bars represent mean ±SD. Mock, n=96 cell; MyoVI KD, n=98cells, from two independent experiments. **** P<0,0001 by Mann-Whitney test. (C)  IF analysis of  PCM1 signal. hTERT-RPE1 cells were treated with Nutlin-3 for 24 hours and immunostained  with anti-PCM1 and anti-Cep135 antibodies. Panels as in B. Mock, n=96 cells; Nutlin-3, n=100 cells, from two independent experiments. **** P<0,0001 by Mann-Whitney test. (D)  IF  analysis of PCM1 signal. hTERT-RPE1 p53 KO cells were transfected with siRNA against  myosin VI and immunostained with anti-PCM1 and anti-Cep164  antibodies. Panels as in B. Quantification of PCM1 intensity refers to a 3 μm circle around the mother centriole, identified with anti-Cep164 staining. Mock, n=128 cells; MyoVI KD, n=114 cells from three independent experiments. ns, not significant by Mann-Whitney test.",
    "ncbi_link": "myosin VI: 4646
MyoVI: 4646
p53: 7157"
  },
  {
    "caption": "(B)  IF  analysis of  OFD1 signal at the centriolar satellites  upon   serum starvation. hTERT-RPE1 p53  KO cells were transfected with siRNA against myosin VI. After four days, cells were fixed (growing) or  serum starved for 24 hours (SS). Cells were immunostained  with anti-OFD1  and anti-PCM1 antibodies. The intensity of OFD1  signal in the area covered by PCM1  was quantified and normalised against the intensity of PCM1 staining in the same area. Left, representative images, scale bar, 2 μm. Right, results are expressed as fold change with respect to mock average intensity. Bars represent mean ±SD. Mock_growing, n=150 cells; Mock_SS, n=149 cells; MyoVI  KD_growing, n=149 cells;  MyoVI  KD_SS, n=150 cells, from three independent experiments. ns, not significant; * P<0,05; **** P<0,0001 by Kruskal-Wallis test.",
    "ncbi_link": "myosin VI: 4646
MyoVI: 4646
p53: 7157"
  },
  {
    "caption": "(C) IB  analysis of OFD1 after  serum starvation in control and myosin VI-depleted cells.  hTERT-RPE1 p53 KO cells were transfected with siRNA against myosin VI. After four days, cells were  serum starved   for 24 hours (SS). Lysates were analysed by IB  with anti-OFD1, anti-myosin VI, anti-p62, and anti-LC3 antibodies. Anti-GAPDH was used as loading control. The amount of  OFD1 protein was normalised against  GAPDH signal and is expressed as percentage of OFD1  levels in cells grown in  serum-starved  conditions compared to cells grown in media containing  serum. Bars represent mean ±SD. n=5 independent experiments. * P<0,05 by Kruskal-Wallis test.",
    "ncbi_link": "myosin VI: 4646
p53: 7157"
  },
  {
    "caption": "(D) IF analysis of primary cilium  upon  serum starvation. hTERT-RPE1 p53  KO cells were transfected with siRNA against  myosin VI. After four days, cells were fixed (growing) or serum starved    for 24 hours (SS). Cells were immunostained with anti-acetylated tubulin (to identify the  cilia), anti-Cep135 (to identify the centrioles) and  DAPI. Left, representative images, scale bar, 2 μm. Right, results are expressed as fold change with respect to mock average intensity. Bars represent mean ±SD. n=3 independent experiments. 100-200 cells/condition were counted for each experiment. ***P < 0.001 by two-way ANOVA test.",
    "ncbi_link": "myosin VI: 4646
p53: 7157"
  },
  {
    "caption": "B, C MCF-7  cells expressing GFP-INPP4B  or GFP-vector were cultured in growth media or EBSS  for the indicated times, then lysed and immunblotted  with LC3B   antibodies and GAPDH  antibodies as a loading control (B). Data represent the relative LC3B-II levels normalized to GAPDH, and expressed relative to growth media-treated GFP-vector cells which were assigned an arbitrary value of 1 (n=3 experiments) (C). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA with Tukey post hoc test in C,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "D, E MCF-7  cells expressing NT, INPP4B  #1 or INPP4B  #2 shRNA were cultured in  growth media  or EBSS  for the indicated times, then lysed and immunblotted  with LC3B  antibodies and GAPDH  antibodies as a loading control (D). Data represent the relative  LC3B-II levels normalized to GAPDH, and expressed relative to  growth media-treated NT shRNA cells which were assigned an arbitrary value of 1 (n=3 experiments) (E). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA in E.",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "F, G MCF-7  cells expressing GFP-INPP4B  or GFP-vector were cultured in growth media or EBSS  for 4 hours, then fixed and immunostained  with p62  antibodies, and co-stained  with DAPI  and phalloidin  (F). Data represent the number of p62+ puncta relative to cell area (µm2) (n=3 experiments, >50 cells/experiment) (G). Data information: Data is presented as mean ± SD. The insets at the lower right of each image are higher power regions of the boxed areas. Scale bar is 10 µm in F p values determined by one-way ANOVA with Tukey post hoc test in G,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "H, I MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 100 nM bafilomycin A1  or DMSO  as a vehicle control for 4 hours, then lysed and immunblotted  with LC3B  antibodies and GAPDH  antibodies as a loading control (H). Data represent the relative  LC3B-II  levels normalized to GAPDH, and expressed relative to DMSO-treated GFP-vector cells which were assigned an arbitrary value of 1 (I) (n=3 experiments). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA with Tukey post hoc test in , I,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "J, K MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 100 nM bafilomycin A1 or DMSO  as a vehicle control for 4 hours, then fixed and immunostained  with p62  antibodies, and co-stained with DAPI  and phalloidin  (J). Data represent the number of p62+ puncta relative to cell area (µm2) (n=3 experiments, >50 cells/experiment) (K). Data information: Data is presented as mean ± SD. The insets at the lower right of each image are higher power regions of the boxed areas. Scale bar is 10 µm in J. p values determined by one-way ANOVA with Tukey post hoc test in K,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "L, M MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 2 µM BYL719  or DMSO  as a vehicle control for the indicated times. Cells were lysed and immunblotted  with LC3B, pAKTS473, AKT(pan), pS6KT389 or S6K  antibodies and GAPDH  antibodies as a loading control (L). Data represent the relative LC3B-II levels normalized to GAPDH, and expressed relative to DMSO-treated GFP-vector cells which were assigned an arbitrary value of 1 (n=3 experiments) (M). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA with Tukey post hoc test in M,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "N, O MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 1 µM or 10 µM SAR405  or DMSO  as a vehicle control for 4 hours. Cells were lysed and immunblotted  with LC3B  antibodies and GAPDH antibodies as a loading control (N). Data represent the relative LC3B-II levels normalized to GAPDH, and expressed relative to DMSO-treated GFP-vector cells which were assigned an arbitrary value of 1 (n=3 experiments) (O). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA with Tukey post hoc test in O,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "A, B MCF-7 cells expressing NT, INPP4B  #1 or INPP4B  #2 shRNA were fixed and immunostained  with recombinant GST-2xFYVE and LAMP2  antibodies, and  co-stained  with DAPI  (A). Data represent the proportion of 2xFYVE+ lysosomes  (n=3 experiments, >40 cells/experiment) (B). Arrows indicate  co-localization  between 2xFYVE and LAMP2. Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in A, p values determined by one-way ANOVA with Tukey post hoc test in B",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "D, E MCF-7  cells co-expressing GFP-INPP4B  or GFP-vector, and Hrs  or NT shRNA, were fixed and immunostained  with recombinant GST-2xFYVE and LAMP2  antibodies, and co-stained  with DAPI  (D). Data represent the proportion of 2xFYVE+ lysosomes  (n=3 experiments, >30 cells/experiment) (E). Arrows indicate  co-localization  between 2xFYVE and LAMP2. Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in D, p values determined by one-way ANOVA with Tukey post hoc test in",
    "ncbi_link": "GFP: 
INPP4B: 8821
Hrs: 6430"
  },
  {
    "caption": "F, G  MCF-7 cells co-expressing GFP-INPP4B  or GFP-vector, and Hrs  or NT shRNA, were fixed and immunostained  with recombinant GST-2xFYVE   and CD63  antibodies, and co-stained  with DAPI  (F). Data represent the proportion of 2xFYVE+ late endosomes (n=3 experiments, >30 cells/experiment) (G). Arrows indicate co-localization between 2xFYVE and LAMP2. Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in F. p values determined by one-way ANOVA with Tukey post hoc test in G,",
    "ncbi_link": "GFP: 
INPP4B: 8821
Hrs: 6430"
  },
  {
    "caption": "H, I MCF-7 cells co-expressing GFP-INPP4B  or GFP-vector, and Hrs  or NT shRNA, were lysed and immunoblotted  with LC3B  antibodies, and GAPDH  antibodies as a loading control (H). Data represent the relative LC3B-II levels normalized to GAPDH, and expressed relative to GFP-vector;NT shRNA cells which were assigned an arbitrary value of 1 (n=3 experiments) (I). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA in I.",
    "ncbi_link": "GFP: 
INPP4B: 8821
Hrs: 6430"
  },
  {
    "caption": "A, B MCF-7  cells expressing GFP-INPP4B  or GFP-vector were fixed and immunostained  with LAMP1  or LAMP2  antibodies, and co-stained with DAPI  and phalloidin  (A). Data represent the number of LAMP1+ or LAMP2+ puncta relative to cell area (µm2) (n=3 experiments, >50 cells/experiment) (B). Data information: Data is presented as mean ± SD. Scale bar is 10 µm in A, p values determined by two-tailed unpaired t test in B,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "C, D Snapshots of  Magic Red cathepsin B   substrate and Hoechst 33342  captured in live MCF-7 cells expressing GFP-INPP4B  or GFP-vector (C). Data represent the number of  Magic Red cathepsin B+ puncta per cell (n=3 experiments, >50 cells/experiment) (D). Data information: Data is presented as mean ± SD. Scale bar is 10 µm in C, p values determined by two-tailed unpaired t test in D,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "E, F MCF-7 cells expressing NT or INPP4B  #1 shRNA were cultured in growth media  or EBSS  for the indicated times, then fixed and immunostained  with LAMP1  antibodies and co-stained  with DAPI  and phalloidin  (E). Data represent the number of LAMP1+ puncta relative to cell area (µm2) (n=3 experiments, >30 cells per experiment) (F). Data information: Data is presented as mean ± SD. Scale bar is 10 µm in p values determined by one-way ANOVA with Tukey post hoc test in F",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "G, H  MCF-7  cells expressing GFP-INPP4B  or GFP-vector were transfected with NT, PIK3CA  #1 or PIK3CA  #2 siRNA. After 24 hours, cells were fixed and immunostained  with LAMP1  antibodies, and co-stained with DAPI  and phalloidin  (G). Data represent the number of LAMP1+ puncta relative to cell area (µm2) (n=3 experiments, >40 cells per experiment) (H). Data information: Data is presented as mean ± SD. Scale bar is 10 µm in G. p values determined by one-way ANOVA in H.",
    "ncbi_link": "GFP: 
INPP4B: 8821
PIK3CA: 5290"
  },
  {
    "caption": "A, B Snapshots of LAMP1-GFP, Magic Red cathepsin B  substrate and  Hoechst 33342 captured in live HeLa  cells transfected with INPP4B  or NT siRNA (A). Data represent the number of LAMP1+/Magic Red Cathepsin B+ and LAMP1+/Magic Red Cathepsin B− lysosomes   (terminal storage lysosomes) per cell (n=3 experiments, >50 cells/experiment) (B).Yellow arrows indicate LAMP1+/MR Cathepsin B+ lysosomes, and white arrows indicate terminal storage lysosomes. Data information: Data is presented as mean ± SD. The insets at the lower right of each image are higher power regions of the boxed areas. Scale bar is 10 µm in A, p values determined by two-way ANOVA with Holm-Sidak post-hoc test in B",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "C Timelapse  snapshots of LAMP1-mCherry  signals from MCF-7 cells expressing GFP-INPP4B  or GFP-vector captured by  spinning disk microscopy. Maximum intensity projections of 3 z-planes taken 0.27 µm apart are shown. Arrows indicate lysosome  reformation. Data information: The insets at the lower right of each image are higher power regions of the boxed areas. Scale bar is 10 µm in C.",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "E Data represent the number of LAMP1+ reformation events per cell per minute (n=12 GFP-vector cells, n=15 GFP-INPP4B  cells). Data information: Data is presented as mean ± SD. p values determined by two-tailed unpaired t test in E.",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "A, B  MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 5 µM YM201636  for 2 hours. Cells were fixed and immunostained  with recombinant GST-2xFYVE and LAMP2  antibodies, and co-stained with DAPI  (A). Data represent the proportion of 2xFYVE+ lysosomes  (n=3 experiments, >30 cells/experiment) (B). Arrows show co-localization between 2xFYVE and LAMP2. Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in A p values determined by one-way ANOVA in B",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "D-F  MCF-7  cells expressing GFP-INPP4B  or GFP-vector were treated with 5 µM YM201636  or DMSO  as a vehicle control for 2 hours, then YM201636  was washed out for 1, 2 or 4 hours. Cells were fixed and immunostained  with LAMP1  antibodies, and co-stained  with DAPI  and phalloidin  (D). Data represent the number of LAMP1+ puncta relative to cell area (µm2) (E), and the lysosome  fold change relative to the YM201636-treated condition for each cell line (F) (n=3 experiments, >30 cells per experiment). Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in D. p values determined by one-way ANOVA in E, or by two-tailed unpaired t test of the area under the curve in F.",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "G, H MCF-7 cells expressing GFP-INPP4B  or GFP-vector were treated with 1, 2 or 5 µM YM201636  or DMSO  as a vehicle control for 4 hours. Cells were lysed and immunoblotted  with LC3B  antibodies, and GAPDH  antibodies as a loading control (G). Data represent the relative LC3B-II levels normalized to GAPDH, and expressed relative to DMSO-treated GFP-vector cells which were assigned an arbitrary value of 1 (n=3 experiments) (H). Data information: Data is presented as mean ± SD. p values determined by one-way ANOVA in H,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "A, B MCF-7  cells expressing GFP-INPP4B  or GFP-vector were transfected with NT, SNX1  or SNX2  siRNA. After 24 hours, cells were fixed and immunostained  with LAMP2  antibodies, and  co-stained with DAPI  and phalloidin  (A). Data represent the number of LAMP2+ puncta relative to cell area (µm2) (n=3 experiments, >40 cells per experiment) (B). Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in A, p values determined by one-way ANOVA in with Tukey post hoc test in B",
    "ncbi_link": "GFP: 
INPP4B: 8821
SNX1: 6642
SNX2: 6643"
  },
  {
    "caption": "D, E MCF-7  cells expressing GFP-INPP4B  or GFP-vector were treated with 5 µM YM201636  for 2 hours, then YM201636  was washed out for 1 hour. Cells were fixed and immunostained  with SNX2  and LAMP1  antibodies, and co-stained with DAPI  (D). Data represent the proportion of SNX2+ LAMP2  puncta (n=3 experiments, >40 cells/experiment) (E). Arrows show  co-localization between SNX2  and LAMP2. Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in D, p values determined by one-way ANOVA in with Tukey post hoc test in E,",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "F HeLa  cells were transfected with GFP-SNX2. After 24 hours, cells were treated with 5 µM YM201636  for 2 hours, then YM201636  was washed out for 1 hour. Cells were fixed and subjected to  immuno-electron microscopy  analysis using GFP  (10 nm) antibodies. Arrows show GFP-SNX2 localization  to lysosome. Data information: Scale bar is 100 nm in F.",
    "ncbi_link": "GFP: 
SNX2: 67804"
  },
  {
    "caption": "G HeLa  cells were transfected with GFP-PIKfyve. After 24 hours, cells were were treated with 5 µM YM201636  for 2 hours, then YM201636  was washed out for 1 hour. Cells were fixed and immunostained  with SNX2, GFP  and LAMP2  antibodies, and imaged using super resolution microscopy. Arrows show  co-localization  between GFP-PIKfyve, SNX2  and LAMP2. Data information: The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in",
    "ncbi_link": "GFP: 
PIKfyve: 200576"
  },
  {
    "caption": "H  MCF-7 cells expressing LAMP1-mCherry   were transfected with NT or SNX2  siRNA. After 24 hours, cells were imaged by spinning disk microscopy for 20 minutes. Representative timelapse  snapshots of LAMP1-mCherry  from a maximum projection of 3 z-planes taken 0.27 µm apart are shown. Arrow indicates lysosome fission. I Data represent the number of LAMP1+ reformation events per cell per minute (n=21 NT siRNA cells, n=27 SNX2  siRNA cells). Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in H, p values determined by two-tailed unpaired t test in I.",
    "ncbi_link": "mCherry: 
LAMP1: 25328
SNX2: 6643"
  },
  {
    "caption": "A, B HeLa   cells transfected with INPP4B  or NT siRNA were treated for 1 hour with 5 µg/mL puromycin. Cells were fixed and immunostained  with ubiquitin  antibodies, and co-stained  with DAPI  and phalloidin (A). Data represent the percentage of cells with ubiquitinated  protein aggregates (n=3 experiments, >200 cells/experiment) (B). Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in A p values determined by one-way ANOVA in with Tukey post hoc test in B",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "E, F MCF-7  cells expressing GFP-INPP4B  or GFP-vector were treated for 4 hours with 10 µg/mL puromycin, 5 µm MG132  and either 5 µM YM201636  or DMSO  as a vehicle control. Cells were fixed and immunostained  with ubiquitin  antibodies, and co-stained with DAPI  and phalloidin  (E). Data represent the percentage of cells with ubiquitinated  protein aggregates (n=3 experiments, >200 cells/experiment) (F). Data information: Data is presented as mean ± SD. The insets at the lower right or bottom of each image are higher power regions of the boxed areas. Scale bar is 10 µm in E. p values determined by one-way ANOVA in with Tukey post hoc test in",
    "ncbi_link": "GFP: 
INPP4B: 8821"
  },
  {
    "caption": "G HeLa  cells transfected with INPP4B  or NT siRNA were treated with 10 µg/mL puromycin  for 2-6 hours, then cell viability was assessed using CellTiter-Glo® assays. Data represent the relative  cell viability normalized to untreated NT siRNA cells (n=3 experiments). Data information: p values determined by two-tailed unpaired t test of the area under the curve in G",
    "ncbi_link": "INPP4B: 8821"
  },
  {
    "caption": "a, Wild-type (WT) and Park2-/- BMDMs were infected with mCherry-expressing M. tuberculosis (Mtb) for 4 h and immunostained using anti-parkin antibodies.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "d, U937 human macrophages expressing a scrambled shRNA (Control) or one of two different shRNAs targeting PARK2 (shRNA no. 1, shRNA no. 2) were infected with mCherry-expressing M. tuberculosis for 12 h and immunostained for polyubiquitin.",
    "ncbi_link": "PARK2: 5071"
  },
  {
    "caption": "d, U937 human macrophages expressing a scrambled shRNA (Control) or one of two different shRNAs targeting PARK2 (shRNA no. 1, shRNA no. 2) were infected with mCherry-expressing M. tuberculosis for 12 h and immunostained for polyubiquitin. e, Quantification of ubiquitin positive M. tuberculosis from d, results are means ± s.e.m. of three independent experiments (**P  0.005, Student's t-test). f, The parkin and actin expression in cells from e was determined by western blotting.",
    "ncbi_link": "PARK2: 5071"
  },
  {
    "caption": "g, Park2−/− BMDMs were transduced with lentivirus expressing BFP (−), wild-type parkin, or two separate mutant parkin alleles (T240R, P437L). Cells were infected with M. tuberculosis for 4 h and ubiquitin and M. tuberculosis co-localization was quantified and expressed relative to control BMDMs. Results are means ± s.e.m. of three independent experiments (**P  0.005, paired Student's t-test). h, The parkin and actin expression in cells from g was determined by western blotting.",
    "ncbi_link": "Park2: 50873
parkin: 50873"
  },
  {
    "caption": "g, RAW264.7 macrophages transduced with lentivirus expressing green fluorescent protein (GFP) or parkin were infected with M. tuberculosis and c.f.u. were determined after 16 h. Results were normalized to GFP-expressing cells (n = 3 per group, **P < 0.0076).",
    "ncbi_link": "parkin: 50873"
  },
  {
    "caption": "h, U937 human macrophages expressing either scrambled or PARK2 shRNAs were infected with M. tuberculosis for 36 h and c.f.u were determined. Results were normalized to t = 0 (N = 3 per group, *P< 0.02). All errors, s.e.m.",
    "ncbi_link": "PARK2: 5071"
  },
  {
    "caption": "a, WT and Park2-/- mice were infected with wild-type M. tuberculosis by aerosol and lung bacterial burdens were determined by plating (means ± s.d., n = 5 per group, *P < 0.02 by Student's t-test).",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "c, Survival of M. tuberculosis-infected wild-type and Park2-/- mice (n = 10, **P < 0.001 by log-rank test).",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "a, Wild-type and two independent parkin-deficient D. melanogaster lines (parkc00062, parkf01950) were infected with L. monocytogenes by anterior abdomen injection. Atg8 processing was monitored in whole-fly protein lysates by western blotting.",
    "ncbi_link": "parkin: 40336"
  },
  {
    "caption": "Single plane confocal fluorescent microscopy images of 5-day-old animals harboring GFP-tagged endogenous HSP-110 (HSP-110::GFP). Muscle cells are outlined. M: muscle, H: hypodermis. In animals that co-express hairpin constructs targeting hsp-110 in muscle cells (HSP-110;HPI and HSP-110;HPII), GFP fluorescence is strongly reduced in muscle cells in comparison to control animals, indicating HSP-110::GFP depletion specifically in muscle cells. Scale bar: 10 µm.",
    "ncbi_link": "GFP: 
hsp-110: 176195"
  },
  {
    "caption": "Experimental set-up: Age-synchronized 4-day-old animals were subjected to heat stress for 3 h at 33°C (+HS) then returned to 20°C or left at 20°C (-HS), respectively. Arrows indicate imaging time points. The -HS controls were imaged at the same time point as the +HS animals after 24h at 20°C. Maximum intensity projections of fluorescent microscopy z-stacks of animals expressing the indicated transgenes. HS-induced FLUCSM::GFP foci are cleared after a recovery for 24h at 20°C in the WT background, but persist in the presence of the hsp-110 hairpin construct. Scale bar: 20 µm. C Quantification of FLUCSM::GFP foci disaggregation. % disaggregation is calculated as 100 - ratio of FLUCSM::GFP foci area relative to total muscle area at the +HS 24h time point to the +HS 2h time point. Data are displayed as mean ± SEM (in %) (N = 3). Statistical analysis was done using one-way ANOVA with Dunnett's adjustment for multiple comparisons. ** p ≤ 0.01. Data information: All strains harbor the sid-1(pk3321) allele. ",
    "ncbi_link": "hsp-110: 176195
sid-1: 178900"
  },
  {
    "caption": "A Maximum intensity projections of fluorescent microscopy z-stacks of 5-day-old nematodes expressing the indicated transgenes are shown. White dashed lines outline the borders of muscle cells. Scale bar: 10 µm. The co-expression of HPI and HPII reduces the amount of α-Syn::YFP inclusions. B Quantification of α-Syn::YFP foci in 3- to 6-day-old animals. Product of mean foci fluorescence and foci area relative to muscle area is displayed (relFluoFoci). Data are shown as mean ± SEM (in %) (N = 3). Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. ** = p ≤ 0.01, *** p ≤ 0.001. ",
    "ncbi_link": "α-Syn: 6622"
  },
  {
    "caption": "D Maximum intensity projections of fluorescent microscopy z-stacks of 6-day-old animals expressing the indicated transgenes. Scale bar: 100 µm. The co-expression of HPI and HPII reduces the amount of Q35::YFP inclusions.",
    "ncbi_link": "Q35: "
  },
  {
    "caption": "E Quantification of Q35::YFP foci in WT and hsp-110 hairpin background. Shown is the mean ± SEM (N = 3). Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. * p ≤ 0.05, ** p ≤ 0.01.",
    "ncbi_link": "hsp-110: 176195"
  },
  {
    "caption": "G Maximum intensity projections of fluorescent microscopy z-stacks of of 5-day-old nematodes expressing the indicated transgenes. White dashed lines outline the borders of muscle cells. Scale bar: 10 µm. M: muscle, H: hypodermis. Signal outside of muscle cells reveals spreading of α-Syn. H Quantification of animals showing α-Syn transmission at indicated ages. Displayed is the mean ± SEM (in %) (N = 4). Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. *** p ≤ 0.001. ",
    "ncbi_link": "α-Syn: 6622"
  },
  {
    "caption": "A Maximum intensity projections of confocal microscopy z-stacks of 5-day-old animals expressing the indicated transgenes. White dashed lines outline the borders of muscle cells. Scale bar: 10 µm. The expression of the yeast SSE1N575Y E575A mutant cannot reverse the reduction of α-Syn::YFP foci in the hsp-110 hairpin expressing animals.",
    "ncbi_link": "hsp-110: 176195
SSE1: 855998"
  },
  {
    "caption": "B Quantification of motility as a measure for transgene toxicity. Displayed is the mean ± SEM (N = 3) amount of body bends/30s of animals expressing the indicated transgenes. Statistical analysis was done using two-way ANOVA and with Dunnett's multiple comparison test. n.s. = not significant, ** p ≤ 0.01, *** p ≤ 0.001. The presence of the yeast SSE1N575Y E575A mutant was not able to suppress the rescue of α-Syn::YFP toxicity in hsp-110 hairpin expressing animals.",
    "ncbi_link": "hsp-110: 176195
SSE1: 855998"
  },
  {
    "caption": "E Experimental set-up: Age-synchronized 4-day-old animals were subjected to heat stress for 3 h at 33°C (+HS) then returned to 20°C or left at 20°C (-HS), respectively. Arrows indicate imaging time points. The -HS controls were imaged at the same time point as the +HS animals after 24h at 20°C. Maximum intensity projections of fluorescent microscopy z-stacks of animals expressing the indicated transgenes. Scale bar: 20 µm. The impaired clearance of HS-induced FLUCSM::GFP foci in the hsp-110 hairpin expressing cells is rescued by co-expression of WT but not by the HSP-70 binding deficient SSE1N575Y E575A mutant.",
    "ncbi_link": "hsp-110: 176195
SSE1: 855998"
  },
  {
    "caption": "F Quantification of FLUCSM::GFP foci disaggregation. % disaggregation is calculated as 100 - ratio of FLUCSM::GFP foci area relative to total muscle area at the +HS 24h time point to the +HS 2h time point. Data are displayed as mean ± SEM (in %) (N = 3). Statistical analysis was done using one-way ANOVA with Dunnett's multiple comparison test. n.s. = not significant, ** p ≤ 0.01. All strains harbor the sid-1(pk3321) allele. ",
    "ncbi_link": "sid-1: 178900"
  },
  {
    "caption": "A Maximum intensity projections of confocal z-stacks of 4-day-old animals expressing the indicated transgenes or harboring the indicated temperature-sensitive (ts) mutations. Muscle cells were stained with anti-myosin (green) and Alexa Flour 647-phalloidin (purple). Scale bar: 5 µm. Myosin misfolding reflects the exposure of the ts mutant phenotype of myosin(ts) [unc-54(e1301)] at the permissive temperate of 15°C by co-expression of the hsp-110 hairpins.",
    "ncbi_link": "hsp-110: 176195"
  },
  {
    "caption": "B Quantification of motility as a measure for toxicity. Displayed is the mean ± SEM (N = 4) of body bends/30s of animals expressing the indicated transgenes or harboring the indicated mutations. Statistical analysis was done using one-way ANOVA with Dunnett's multiple comparison test. *** p ≤ 0.001. Co-expression of the hsp-110 hairpins exposed the ts mutant phenotype at the permissive temperate of 15°C, resulting in a significant increase in movement defects. All strains contain the sid-1(pk3321) allele.",
    "ncbi_link": "hsp-110: 176195
sid-1: 178900"
  },
  {
    "caption": "C Quantification of motility as a measure for transgene toxicity. Displayed is the mean ± SEM (N = 4) amount of body bends/30s of animals expressing the indicated transgenes or harboring the indicated mutations. Statistical analysis was done using two-way ANOVA with Tukey's multiple comparison test. * p ≤ 0.05. Expression of the hsp-110 hairpins caused movement defects with increasing age.",
    "ncbi_link": "hsp-110: 176195"
  },
  {
    "caption": "D Maximum intensity projections of confocal z-stacks of 12-day-old animals expressing the indicated transgenes. Scale bar: 10 µm. FLUCSM forms foci with increasing age, which is markedly accelerated upon hsp-110 KD.",
    "ncbi_link": "hsp-110: 176195"
  },
  {
    "caption": "F Quantification of motility as a measure for transgene toxicity. Displayed is the mean ± SEM (N = 3) amount of body bends/30s of animals expressing the indicated transgenes or harboring the indicated mutations. Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. n.s. = not significant, *** p ≤ 0.001. Expression of the hsp-110 hairpins caused movement defects with increasing age. The beneficial effects of HSP-110 KD on amyloid toxicity is masked in older animals.",
    "ncbi_link": "hsp-110: 176195
HSP-110: 176195"
  },
  {
    "caption": "G Quantification of motility as a measure for transgene toxicity. Displayed is the mean ± SEM (N = 3) amount of body bends/30s of animals expressing the indicated transgenes or harboring the indicated mutations. Statistical analysis was done using two-way ANOVA with Dunnett's multiple comparison test. n.s. = not significant, , ** p ≤ 0.01, *** p ≤ 0.001. Expression of the hsp-110 hairpins caused movement defects with increasing age. The beneficial effects of HSP-110 KD on amyloid toxicity is masked in older animals. Data information: All strains harbor the sid-1(pk3321) allele. ",
    "ncbi_link": "hsp-110: 176195
HSP-110: 176195
sid-1: 178900"
  },
  {
    "caption": "C Representative electron micrographs of VAP double knockout HeLa cells that were either left untreated or incubated with 250 µM LLOMe for 5 min or 10 min before chemical fixation. Cells were incubated with 15 nm gold nanoparticles conjugated to bovine serum albumin for 4 h to visualize lysosomes. After 4 h, gold nanoparticles were washed off and cells were incubated overnight before treatment with LLOMe and processing samples for electron microscopy (same as in A). Quantification of electron micrographs showing no increase in membrane contact sites between ER and lysosomes following 250 µM LLOMe treatment for 5 or 10 minutes in VAP double knockout cells. Error bars denote +/- SD from n=3 independent experiments, >40 lysosomes were quantified per experiment for each condition.",
    "ncbi_link": "VAP: 9217///9218"
  },
  {
    "caption": "B HeLa cells were transfected with control siRNA or siRNA targeting PI4K2A or PI4K2B for 48 h and transiently transfected with the 2xSidM-eGFP probe to monitor PtdIns4P recruitment after LLOMe-treatment by live-cell imaging. Representative movie stills show the dynamics of 2xSidM-eGFP recruitment in control, PI4K2A and PI4K2B depleted cells. The graph represents the quantification of 2xSidM-eGFP foci per cell after LLOMe-treatment. Error bars denote +/- SEM from n=3 independent live-cell imaging experiments, >25 cells were analyzed per experiment for each condition.",
    "ncbi_link": "PI4K2A: 55361
PI4K2B: 55300"
  },
  {
    "caption": "C CRISPR-Cas9 mediated knockout of PI4K2A abolishes recruitment of the 2xSidM-eGFP probe (PtdIns4P) to damaged lysosomes. Two different clones (clone 2 and clone 3) were tested. The graph represents the quantification of 2xSidM-eGFP foci per cell after LLOMe-treatment. Error bars denote +/- SD from n=2 independent live-cell imaging experiments, >20 cells were analyzed per experiment for each condition.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
PI4K2A: 55361"
  },
  {
    "caption": "D Representative movie stills from live fluorescence microscopy showing reduced eGFP-ORP1L recruitment in PI4K2A knockout cells compared to wild type HeLa cells upon treatment with 250 µM LLOMe. The graph represents the quantification of eGFP-ORP1L foci per cell after LLOMe treatment. Error bars denote +/- SEM from n=4 independent live-cell imaging experiments, >80 cells were analyzed per experiment for each condition.",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "Representative movie stills from live-cell imaging experiments monitoring Lysotracker recovery after induced lysosomal damage using 250 µM LLOMe. Cells were pre-treated with 75 nM Lysotracker Deep Red for 30 min before addition of LLOMe. The graph represents the quantification of bright Lysotracker positive foci per cell. While the decrease in the number of Lysotracker spots is quickly recovering in HeLa cells, there is a severe impairment in lysosomal repair in HeLa-PI4K2A-KO cells.",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "A HeLa cells were co-transfected with siRNAs targeting ESCRT proteins TSG101 and ALIX (siTSG101+siALIX) or with non-targeting siRNA control (siControl), and incubated for 24 h before transfection with the PtdIns4P binding probe 2xSidM-eGFP. 24 h post-transfection lysosomes were damaged with 250 µM LLOMe and PtdIns4P recruitment to damaged lysosomes was monitored using the 2xSidM-eGFP probe in live-cell imaging experiments. The graph shows quantification of 2xSidM-eGFP foci per cell in cells co-depleted of TSG101+ALIX and control (siControl) cells.",
    "ncbi_link": "ALIX: 10015
TSG101: 7251"
  },
  {
    "caption": "D HeLa cells expressing an eGFP-tagged ORP1L mutant incapable of binding to VAP (mFFAT) show no accumulation of the cholesterol reporter mCherry-D4 upon lysosomal damage induced with 250 µM LLOMe when compared to wildtype (wt) eGFP-ORP1L. The quantification graph shows D4-mCherry foci per cell. Error bars denote +/- SEM from n=4 independent live-cell imaging experiments, >50 cells were analyzed per experiment for each condition.",
    "ncbi_link": "eGFP: 
ORP1L: 114876
VAP: 9217///9218"
  },
  {
    "caption": "D Knock down efficiency of siRNA depletion of OSBP in HeLa cells as detected by Western blot. β-actin used as a loading control.",
    "ncbi_link": "OSBP: 5007"
  },
  {
    "caption": "Conditioned medium was collected from pericytes 48 h after adenoviral transduction. Western blotting verified the secretion of Sema3CΔ13 (81 kDa) and Sema3Cp60 (60 kDa) isoforms.",
    "ncbi_link": "Sema3C: 10512"
  },
  {
    "caption": "HUVECs were suspended in conditioned medium with VEGF (25 ng/ml) and plated on Matrigel. Branch points of the capillary-like network were counted after 18 h. n = 4 independent experiments; scale bar, 200 μm. Control vs. Sema3C, *P = 0.0375 and control vs. Sema3CΔ13, *P = 0.0162.",
    "ncbi_link": "Sema3C: 10512"
  },
  {
    "caption": "HUVEC spheroids in collagen were treated with conditioned medium with or without VEGF (25 ng/ml). After 24 h, the cumulative sprout length per spheroid was quantified. Data are representative of three independent experiments with ten spheroids per group. Scale bar, 100 μm. Control vs. Sema3C (− VEGF), *P = 0.0276; control vs. Sema3CΔ13 (− VEGF), *P = 0.0443; control vs. Sema3C (+ VEGF), *P = 0.028 and control vs. Sema3CΔ13 (+ VEGF), *P = 0.032.",
    "ncbi_link": "Sema3C: 10512"
  },
  {
    "caption": "Microvessels within the plugs stained against human-specific CD34. Cell nuclei were stained with DAPI. Scale bar, 100 μm.The area of CD34-positive microvessels was quantified and normalized to the total area of plug. Results represent the means ± s.e.m of 5 plugs (control) and 7 plugs (Sema3C), *P = 0.018.",
    "ncbi_link": "Sema3C: 10512"
  },
  {
    "caption": "Vessel coverage was assessed by αSMA staining. Scale bar, 100 μm.Vessel coverage was quantified as the ratio of endothelial cell-associated mural cells to total amount of vessels (n = 5 (control) and n = 7 (Sema3C)).Vessel perfusion was evaluated by i.v. injection of FITC-lectin (0.15 mg) 30 min before mice were sacrificed. The data show the percentage of perfused vessels in the plug and normalized to total vessel area (n = 5 (control) and n = 7 (Sema3C)).",
    "ncbi_link": "Sema3C: 10512"
  },
  {
    "caption": "HUVECs were transfected with siRNA against PlexinD1 or control NS (non-silence) siRNA. qPCR analyses and Western blotting were performed after 48 h (n = 3; paired Student's t-test, NS siRNA vs. PlexinD1 siRNA, ***P = 0.0004). Cell lysates were subjected to SDS-PAGE and probed with anti-PlexinD1.",
    "ncbi_link": "PlexinD1: 23129"
  },
  {
    "caption": "HUVECs were transfected with siRNA against PlexinD1 and plated on gelatin-coated coverslips. Confluent monolayers were treated with Sema3C-, Sema3Cp60- or control-conditioned medium for 30 min. Cells were fixed and stained with Alexa-Fluor 488-conjugated phalloidin to visualize F-actin. Arrows indicate Sema3C-induced cell membrane ruffling. Scale bar, 20 μm. Cell repellence was quantified as the number of cells with membrane ruffling normalized to the number of nuclei (n = 5; mean ± s.e.m., paired Student's t-test, **P = 0.001).",
    "ncbi_link": "PlexinD1: 23129"
  },
  {
    "caption": "Silencing of Nrp-1 by lentiviral particles expressing shRNA. After culturing 72 h in selection medium, RNA was harvested for qPCR analysis. NS shRNA vs. Nrp-1 shRNA: #1, *P = 0.017 and #2, *P = 0.02; n = 3; mean ± s.e.m. Cell lysates were subjected to SDS-PAGE and probed with anti-Nrp-1.",
    "ncbi_link": "Nrp-1: 8829"
  },
  {
    "caption": "Depletion of Nrp-1 abolished the response to Sema3C. Sema3Cp60 had no effect on HUVEC adhesion. Arrows indicate membrane ruffling. Scale bar, 20 μm. Cell repellence was quantified as the number of cells with membrane ruffling normalized to the number of nuclei (n = 5; mean ± s.e.m.; paired Student's t-test, ***P = 0.0003).",
    "ncbi_link": "Nrp-1: 8829"
  },
  {
    "caption": "RNA scope analyses showed Sema3C and PlexinD1 expression in pre-retinal tufts (OIR model, P19). The retinae were subsequently stained against collagen IV. Sema3CmRNA was detected in peri-endothelial cells. Scale bar: 20 μm.",
    "ncbi_link": "PlexinD1: 67784
Sema3C: 20348"
  },
  {
    "caption": "H. Subcellular localizations of zRbm14b resembled those of zRbm14a. Zebrafish embryos were microinjected with 400 pg of GFP-Rbm14b mRNA per egg at the 1-cell stage and fixed at 4 hpf.",
    "ncbi_link": "GFP: 
Rbm14b: 402858"
  },
  {
    "caption": "Phenotypes of zRbm14 morphants. Totally 8 ng of ctrl-MO, 14-tMOs, or 14-MOs were co-injected with 100 pg of in-vitro transcribed GFP mRNA (as a tracer) into 1-cell embryos to generate control, maternal zRbm14, and zygotic zRbm14 morphants, respectively. Representative embryos, imaged under a dissecting microscope, are shown in (A)",
    "ncbi_link": "GFP: 
Rbm14: 402858///323721"
  },
  {
    "caption": "Phenotypes of zRbm14 morphants. Totally 8 ng of ctrl-MO, 14-tMOs, or 14-MOs were co-injected with 100 pg of in-vitro transcribed GFP mRNA (as a tracer) into 1-cell embryos to generate control, maternal zRbm14, and zygotic zRbm14 morphants, respectively. phenotyping results in (B). Total numbers of embryos analyzed are listed over histograms. Sample dots are included for quantification results with no error bars.",
    "ncbi_link": "GFP: 
Rbm14: 402858///323721"
  },
  {
    "caption": "Maternal zRbm14 morphants displayed reduced cell proliferation in MZT. Embryos stained with Hoechst 33342 and Pyronin Y to mark the nucleus and the cytoplasm, respectively, were imaged from the animal pole to cover a 10-μm z-depth with a confocal microscope (C). Maximum intensity-projected images (C)",
    "ncbi_link": "Rbm14: 402858///323721"
  },
  {
    "caption": "Maternal zRbm14 morphants displayed reduced cell proliferation in MZT. 30 embryos in each condition were used to quantify cell number (D), cell size (E), and nuclear size (F). Each sample dot represents the average value from each embryo.",
    "ncbi_link": "Rbm14: 323721///402858"
  },
  {
    "caption": "C. Cumulative distribution showing fold changes (FCs) in transcript abundance in control morphants (blue curves) and maternal zRbm14 morphants (red curves) between the indicated stages. Transcript abundances were averaged from two independent experiments.",
    "ncbi_link": "Rbm14: 323721///402858"
  },
  {
    "caption": "E. Cumulative distribution showing FCs of transcript abundance of the indicated clusters between control and maternal zRbm14 morphants.",
    "ncbi_link": "Rbm14: 402858///323721"
  },
  {
    "caption": "F. Relative transcript levels of three typical maternal genes. FCs were calculated relatively to the levels in 2.5-hpf ctrl-MO embryos. org, oogenesis-related; trip10a, thyroid hormone receptor interactor 10a; dnajc5ga, DnaJ (Hsp40) homolog, subfamily C, member 5 gamma a.",
    "ncbi_link": "DnaJ (Hsp40) homolog: 322863
dnajc5ga: 322863
member 5 gamma a: 322863
subfamily C: 322863
oogenesis-related: 100001110
org: 100001110
thyroid hormone receptor interactor 10a: 492762
trip10a: 492762"
  },
  {
    "caption": "G. Whole-mount in situ RNA hybridization of org, trip10a, and dnajc5ga. A representative embryo is shown for each group of at least 26 embryos.",
    "ncbi_link": "dnajc5ga: 322863
org: 100001110
trip10a: 492762"
  },
  {
    "caption": "Depletion of zRbm14 resulted in accumulation of poly(A)-containing maternal mRNAs. Total RNAs purified from the indicated zebrafish embryos were subjected to poly(A) length assays. One set of representative PCR results for org and trip10a (B) As the PCR products of the poly(A)-transcripts mainly emerged as a single band, only intensities of this major band were measured.",
    "ncbi_link": "org: 100001110
Rbm14: 402858///323721
trip10a: 492762"
  },
  {
    "caption": "Depletion of zRbm14 resulted in accumulation of poly(A)-containing maternal mRNAs. Total RNAs purified from the indicated zebrafish embryos were subjected to poly(A) length assays. quantification results from three independent experiments (C) are presented. As the PCR products of the poly(A)-transcripts mainly emerged as a single band, only intensities of this major band were measured.",
    "ncbi_link": "Rbm14: 402858///323721"
  },
  {
    "caption": "D. zParn associated with zRbm14b. GFP-zRbm14b was co-expressed respectively with the indicated RFP fusion proteins in HEK293T cells. Co-immunoprecipitations (co-IP) were performed using anti-GFP beads. Luciferase (Luc)-RFP served as a negative control.",
    "ncbi_link": "Luc: 
Luciferase: 
RFP: "
  },
  {
    "caption": "J. zRbm14b and zParn efficiently co-phase separated in deadenylation experiments. The addition of SDS disrupted the condensates to terminate the deadenylation reaction.",
    "ncbi_link": "Parn: 791461
Rbm14b: 402858"
  },
  {
    "caption": "Co-phase separation with zRbm14b markedly enhanced the deadenylation activity of zParn. RNAs extracted from the indicated samples were subjected to immuno-northern blotting using an antibody against m6A (K). were quantified from five sets of independent results.",
    "ncbi_link": "Parn: 791461
Rbm14b: 402858"
  },
  {
    "caption": "Co-phase separation with zRbm14b markedly enhanced the deadenylation activity of zParn. Relatively proportions of Cap-10m6A-A0 in total RNAs (L) were quantified from five sets of independent results.",
    "ncbi_link": "Parn: 791461
Rbm14b: 402858"
  },
  {
    "caption": "D. Relative transcript levels of Rbm14 in the indicated E4.5 blastocysts based on RNA deep Sequencing results, normalized to those of Gapdh. Six blastocysts were considered as Rbm14-/- embryos because they contained only trace amount of Rbm14 transcript reminiscent of maternal mRNA.",
    "ncbi_link": "Gapdh: 14433
Rbm14: 56275"
  },
  {
    "caption": "Severe down-regulation of Gata6 and Nanog in Rbm14-depleted mouse blastocysts. Representative immunofluorescent images (H) were from single option sections. DAPI stained nuclear DNA. As Gata6, Nanog, and Rbm14 localize to the nucleus in blastocysts",
    "ncbi_link": "Rbm14: 56275"
  },
  {
    "caption": "Severe down-regulation of Gata6 and Nanog in Rbm14-depleted mouse blastocysts. As Gata6, Nanog, and Rbm14 localize to the nucleus in blastocysts, their relative intensity in a cell (I) was quantified as their nuclear immunofluorescent intensity normalized with fluorescent intensity of the nuclear DNA. Five brightest cells were quantified for each embryo.",
    "ncbi_link": "Rbm14: 56275"
  },
  {
    "caption": "CSF PGRN levels do not differ among MC participants carrying a PSEN1, PSEN2 or APP mutation.",
    "ncbi_link": "APP: 351
PSEN1: 5663
PSEN2: 5664"
  },
  {
    "caption": "(A) Serum levels of miR-483-3p/-5p in IPAH patients (n = 139) and HC (n = 95) measured by qPCR. The data are fold change normalized to the averaged level of HC. Data information: Values are expressed as median ± interquartile range. Statistical test: Mann Whitney U test (A)",
    "ncbi_link": "-5p: 619552
miR-483-3p: 619552"
  },
  {
    "caption": "(B) ROC curve with sensitivity and specificity of serum levels of miR-483-3p/-5p for differentiating IPAH patients from HCs at diagnosis (IPAH, n = 139; HC, n = 95). Data information: Values are expressed as median ± interquartile range.",
    "ncbi_link": "-5p: 619552
miR-483-3p: 619552"
  },
  {
    "caption": "(C) Levels of miR-483-3p/-5p associated with PAH risk in 3 groups. IPAH patients were divided into a low risk group (Low) and an intermediate plus high risk group (Inter&high) according to the World Symposium on Pulmonary Hypertension 2018 [14]. Data information: Values are expressed as median ± interquartile range. Statistical test: Kruskal-Wallis U test (C).",
    "ncbi_link": "-5p: 619552
miR-483-3p: 619552"
  },
  {
    "caption": "(D) Levels of miR-483-3p were inversely correlated with serum levels of ET-1 (IPAH, n = 118; HC, n = 95) and IL-6 (IPAH, n = 112; HC, n = 93). Data information: Values are expressed as median ± interquartile range.",
    "ncbi_link": "miR-483-3p: 619552"
  },
  {
    "caption": "(A) CD144-enriched EVs were isolated from serum of IPAH patients (n = 37) and HCs (n = 34). The levels of miR-483-3p/-5p were measured by qPCR. Data information: Values are expressed as median ± interquartile range. Statistical test: Mann Whitney U test.",
    "ncbi_link": "-5p: 619552
miR-483-3p: 619552"
  },
  {
    "caption": "PAECs were transfected with miR-483-3p/-5p mimic or scramble RNA for 36 hr before RNA isolation and then analyzed by RNA-seq. Data are results from two biological repeats. (C) Heat map comparison of log2 fold changes of the indicated genes. Data information: Values are expressed as median ± interquartile range. Statistical test: Mann Whitney U test.",
    "ncbi_link": "-5p: 619552
miR-483-3p: 619552"
  },
  {
    "caption": "PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of miR-483-3p/-5p measured by qPCR Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "-5p: 
miR-483-3p: 
pre-miR-483: 619552"
  },
  {
    "caption": "PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 mRNA were measured by qPCR Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "CTGF: 1490
β-catenin: 1499
ET-1: 1906
IL-1β: 3553
pre-miR-483: 619552
TGF-β: 7040
TGFBR2: 7048"
  },
  {
    "caption": "PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 protein were measured by Western blot Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "pre-miR-483: 619552"
  },
  {
    "caption": "(E) Bovine aortic ECs were transfected with a luciferase reporter fused with the 3'UTR of TGF-β (Luc-TGF-β WT), TGFBR2 (Luc-TGFBR2 WT), IL-1β (Luc-IL-1β WT) or ET-1 (Luc-ET-1 WT) or a binding site mutation (Luc-TGF-β Mut, Luc-TGFBR2 Mut, Luc-IL-1β Mut, ET-1-Mut), then infected with Lenti-pre-miR-483 for additional 36 hr. Luciferase activity was measured. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "Luc: 
luciferase: 
ET-1: 1906
IL-1β: 3553
pre-miR-483: 619552
TGF-β: 7040
TGFBR2: 7048"
  },
  {
    "caption": "PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 36 hr. The Ago1- or Ago2-associated miRNAs and mRNAs were enriched by immunoprecipitation with anti-Ago1 or anti-Ago2. Levels of miR-483-3p/-5p mRNA were detected by qPCR and normalized to those of Ago1 or Ago2 protein. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "-5p: 
miR-483-3p: 
pre-miR-483: 619552"
  },
  {
    "caption": "PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 36 hr. The Ago1- or Ago2-associated miRNAs and mRNAs were enriched by immunoprecipitation with anti-Ago1 or anti-Ago2. Levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 mRNA were detected by qPCR and normalized to those of Ago1 or Ago2 protein. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups",
    "ncbi_link": "CTGF: 1490
β-catenin: 1499
ET-1: 1906
IL-1β: 3553
pre-miR-483: 619552
TGF-β: 7040
TGFBR2: 7048"
  },
  {
    "caption": "(A) Lung ECs were isolated from EC- miR-483 transgenic rats (Tg) and their wild-type littermates (WT), n = 3 in each group. MiR-483-3p/-5p levels were measured by qPCR. Data information: Values are expressed as mean ± SEM.",
    "ncbi_link": "-5p: 100314198
miR-483: 100314198
MiR-483-3p: 100314198"
  },
  {
    "caption": "(B) Serum from WT and Tg rats (n = 6) were collected. MiR-483-3p and -5p associated with CD144 were enriched by immunoprecipitation with anti-CD144. Levels of miR-483-3p/-5p were measured by qPCR. Data information: Values are expressed as mean ± SEM. ",
    "ncbi_link": "-5p: 100314198
MiR-483-3p: 100314198
miR-483-3p: 100314198"
  },
  {
    "caption": "Lung ECs isolated from miR-483-Tg rat and WT littermates were exposed to normoxia or hypoxia (0.2% O2) for 24 hr. Proliferation of ECs were measured by flow cytometry Data information: Values are expressed as mean ± SEM. Data are representative of three independent experiments Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "Lung ECs isolated from miR-483-Tg rat and WT littermates were exposed to normoxia or hypoxia (0.2% O2) for 24 hr. migration of ECs were measured by wound healing assay Data information: Values are expressed as mean ± SEM. Data are representative of three independent experiments Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "Tg and WT rats were injected with saline or MCT. Expression levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 mRNA and protein in lung tissues were measured by qPCR and Western blot, respectively (E). Data information: Values are expressed as mean ± SEM.",
    "ncbi_link": "CTGF: 29576
β-catenin: 84353
ET-1: 24323
IL-1β: 24494
TGF-β: 59086
TGFBR2: 81810"
  },
  {
    "caption": "Tg and WT rats were injected with saline or MCT. Levels of miR-483-3p/-5p in serum and lung tissues were measured by qPCR (F). Data information: Values are expressed as mean ± SEM.",
    "ncbi_link": "-5p: 100314198
miR-483-3p: 100314198"
  },
  {
    "caption": "EC-miR-483-Tg and WT rats were injected with saline or MCT. Analysis of mPAP for the indicated groups (7 rats per group) Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups).",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "EC-miR-483-Tg and WT rats were injected with saline or MCT. Analysis of RV hypertrophy [RV/(LV+S)] for the indicated groups (7 rats per group) Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups).",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "EC-miR-483-Tg rats and WT littermates were injected with SU5416 and then exposed to hypoxia for 3 weeks and had reoxygenation for 2 weeks or injected with DMSO and exposed to normoxia for 5 weeks. Analysis of mPAP (E) for the indicated groups. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups).",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "EC-miR-483-Tg rats and WT littermates were injected with SU5416 and then exposed to hypoxia for 3 weeks and had reoxygenation for 2 weeks or injected with DMSO and exposed to normoxia for 5 weeks. Analysis of RV hypertrophy [RV/(LV+S)] (F) for the indicated groups. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups).",
    "ncbi_link": "miR-483: 100314198"
  },
  {
    "caption": "qPCR analysis of miR-483-3p/-5p in serum from PH (MCT-treated) rats. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "ncbi_link": "-5p: 
miR-483-3p: "
  },
  {
    "caption": "qPCR analysis of miR-483-3p/-5p in lung tissue from PH (MCT-treated) rats. Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "ncbi_link": "-5p: 
miR-483-3p: "
  },
  {
    "caption": "(D) Protein and mRNA levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 measured by Western blot and qPCR, respectively (n = 3×3, samples were pooled from three animals for each assay, and 3 independent experiments [a total of 9 animals] were performed). Data information: Values are expressed as mean ± SEM. Statistical test: t-test (*P < 0.05 vs. respective controls or between the indicated groups",
    "ncbi_link": "CTGF: 29576
β-catenin: 84353
ET-1: 24323
IL-1β: 24494
TGF-β: 59086
TGFBR2: 81810"
  },
  {
    "caption": "(A) U2OS  (left panel), RPE1-hTERT (middle panel), and  HeLa  cells (right panel) were monitored for their sensitivity to the radiomimetic drug NCS using the SRB assay. For each cell line, the following conditions were used: U2OS cells were transfected with a nontargeting siRNA (siCtrl) or an siRNA targeting human POGZ  (siPOGZ-1 or -2); RPE1-hTERT cells were transduced a control shRNA (shCtrl) or a shRNA directed against  human POGZ (shPOGZ-1 or -2); HeLa cells expressing a non-targeting sgRNA (sgCtrl) or a sgRNA targeting human POGZ and sub-cloned (POGZ∆-1 or -2). Cells were pulsed with NCS at the indicated concentrations for 1 hour, replenished with fresh medium and incubated for 4 days before being processed for SRB assays. Data are represented as a bar graph showing the relative mean ± SEM, each replicate being representing as a round symbol (3 biological replicates). Significance was determined by two-way ANOVA followed by a Bonferroni's test. *P<0.01.",
    "ncbi_link": "POGZ: 23126"
  },
  {
    "caption": "(D) U2OS (left panel) and HeLa (right panel) cells containing the DR-GFP reporter construct were transfected with the indicated siRNA. 24h post-transfection. Cells were transfected with the I-SceI  expression plasmid or an empty vector (EV), and the GFP+ population was analyzed 48h post-plasmid transfection. The percentage of  GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition provided with  I-SceI  (siCtrl, I-SceI). Data are represented as the mean ± SEM, each replicate being representing as a round symbol (n=3 biological replicates). Significance was determined by one-way ANOVA followed by a Dunnett's test. *P≤0.0001.",
    "ncbi_link": "I-SceI: 854590"
  },
  {
    "caption": "(F) Quantification of γ-H2AX  foci in  HeLa  cells where POGZ has been targeted by  CRISPR  technology (POGZ∆-1 or -2) and in control HeLa  cells (sgCtrl). Cells were exposed to 1 Gy before being pulsed with  Edu for 1hr and were recovered at the indicated time points. Cells were fixed, stained, and imaged via confocal microscopy. Data are the total number of γ-H2AX foci in EdU+ cells and represented as a bar graph showing the mean ± SD (n = 3 biological replicates, with at least 100 cells analyzed for each  time point). Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.05, **P<0.0005. (G) Representative images used for quantification in (F). Scale bar = 5 μm. ",
    "ncbi_link": "CRISPR: 
POGZ: 23126"
  },
  {
    "caption": "(A) U2OS stably expressing mCherry-LacR-FokI were transfected with the indicated siRNA. 24h post-transfection, DNA damage was induced using Shield1 and 4-OHT. Immunofluorescence  against the indicated DNA repair proteins was subsequently performed to monitor their accumulation at sites of DNA damage by confocal microscopy. Data are represented as a box-and-whisker (10-90 percentile) where the fluorescent signal at the mCherry focus was normalized to nuclear  background. At least 100 cells per condition were counted (n=3 biological replicates). Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.05, **P<0.005, **P≤0.0005.",
    "ncbi_link": "FokI: 
LacR: 
mCherry: "
  },
  {
    "caption": "(B)  U2OS  (left panel), RPE1-hTERT (middle panel), and HeLa cells (right panel) were monitored for their capacity to form IR-induced BRCA1 foci. For each cell line, the following conditions were used: U2OS cells were transfected with a nontargeting siRNA (siCtrl) or an siRNA targeting human POGZ (siPOGZ-1 or -2); RPE1-hTERT  cells were transduced a control shRNA (shCtrl) or a shRNA directed against  human POGZ (shPOGZ-1 or -2); HeLa cells were expressing a non-targeting sgRNA (sgCtrl) or a sgRNA targeting human POGZ and sub-cloned (POGZ∆-1 or -2). Cells were exposed to 1 Gy before being pulsed with  Edu for 1hr and were recovered 1h post-exposure to IR. Cells were fixed, stained, and imaged via confocal microscopy. Data are the total number of ΒRCA1 foci in EdU+ cells and represented as a bar graph showing the mean ± SD (n = 3 biological replicates, with at least 100 cells analyzed for each time point). Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.005, **P<0.001.",
    "ncbi_link": "POGZ: 23126"
  },
  {
    "caption": "(E) U2OS stably expressing  mCherry-LacR-FokI were transduced with the indicated shRNA and subsequently transfected with the indicated siRNA. 24h post-transfection, DNA damage was induced using Shield-1 and  4-OHT. Immunofluorescence against BRCA1 was subsequently performed to monitor its accumulation at sites of DNA damage by confocal microscopy. Data are represented as a box-and-whisker (10-90 percentile) where the fluorescent signal at the mCherry focus was normalized to nuclear  background. At least 50 cells per condition were counted. Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.0001.",
    "ncbi_link": "FokI: 
LacR: 
mCherry: "
  },
  {
    "caption": "(G)  U2OS stably expressing mCherry-LacR-FokI were transduced with the indicated siRNA. 24h post-transfection, DNA damage was induced using Shield-1  and 4-OHT. Immunofluorescence  against the indicated  HP1 isoform was subsequently performed to monitor its respective accumulation at sites of DNA damage by  confocal microscopy. Data are represented as a box-and-whisker (10-90 percentile) where the fluorescent signal at the mCherry focus was normalized to nuclear  background. At least 75 cells per condition were counted. Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.005, **P<0.0001.",
    "ncbi_link": "FokI: 
LacR: 
mCherry: "
  },
  {
    "caption": "(C)  HeLa cells transfected with the indicated construct were monitored for their capacity to form  IR-induced BRCA1 foci. HeLa cells where POGZ has been targeted by  CRISPR technology (POGZ∆-1) and in control HeLa cells (sgCtrl) were transfected by an empty Flag vector (EV) or a sgRNA-resistant FLAG-tagged POGZ  cDNA construct corresponding to indicated rescue mutant (full-length, FL; POGZ801-848, HPZ). Cells were exposed to 1 Gy before being pulsed with  Edu for 1hr and were recovered 1h post-exposure to  IR. Cells were fixed, stained, and imaged via confocal microscopy. Data are the total number of ΒRCA1 foci in EdU+ cells and represented as a bar graph showing the mean ± SD (n = 3 biological replicates, with at least 100 cells analyzed for each time point). Significance was determined by two-way ANOVA followed by a Dunnett's test. *P<0.05, **P<0.0001. (D) Representative images used for quantification in (C). Scale bar = 5 μm. ",
    "ncbi_link": "CRISPR: 
Flag: 
FLAG: 
POGZ: 23126"
  },
  {
    "caption": "Observed genotypic distribution  of offspring of heterozygous Pogz+/∆ crosses at specified embryonic day. Each litter is considered a biological replicate. Data are represented as a bar graph showing the mean ± SEM (n for each embryonic day is specified). (D)",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "(E) The body mass of male wild-type (WT) or Pogz+/∆ mice was monitored weekly for 4 weeks post-weaning. Data are represented as a bar graph showing the mean ± SEM and each mouse  is represented by a round dot (WT) or a square (Pogz+/∆ ). At least 4 mice per genotype was monitored. Significance was determined by two-way ANOVA followed by a Sidak's test. *P<0.05.",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "(H) Quantification of the  distance travelled (left panel) and the average speed (right panel) of each mouse (n=6 mice per genotype) in the open field. Data are represented as a bar graph showing the mean ± SEM and each mouse is represented by a a round dot (WT) or a square (Pogz+/∆ ). Significance was determined by unpaired two-tailed t-test. *P<0.005.",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "(L) Plasma was isolated from  cardiac punctures of wild-type (WT) or Pogz+/∆ mice (8 weeks) and assessed for circulating levels of specified immunoglobulin isotypes. Each mouse is represented by a round dot (WT) or a square (Pogz+/∆ ) (n=6 mice per genotype). Significance was determined by two-way ANOVA followed by a Bonferroni's test. *P<0.005.",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "(A) Wild-type (WT) and Pogz+/∆ mice were subjected to a lethal dose of ionizing radiation (8.5 Gy) before recovering in sterile conditions and being assessed for their sensitivity to  IR. Data are represented as a Kaplan-Meier survival curve of each genotype ((n=6 mice per genotype). Significance was determined by log-rank (Mantel-Cox) test. *P<0.005.",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "(D) MEFs  were monitored for their sensitivity to the radiomimetic drug phleomycin using the SRB assay. Immortalized MEFS obtained from the indicated genotype were treated with increasing concentrations of phleomycin for 1hr, replenished with fresh medium and incubated for 4 days before being processed for SRB assays. Data are represented as a bar graph showing the relative mean ± SEM, each replicate being representing as a round dot (WT) or a square (Pogz+/∆ ). Significance was determined by two-way ANOVA followed by a Bonferroni's test. *P<0.005, **P<0.0005.",
    "ncbi_link": "Pogz: 229584"
  },
  {
    "caption": "Tfeb expression in the vasculature (mice n=10). (A) Representative images of retinal vessels (p5) (A) (scale bar: 50 µm) of Tfeb-EGFP mice stained with anti-iB4 (A) and anti-GFP",
    "ncbi_link": "EGFP: 
Tfeb: 21425"
  },
  {
    "caption": "Tfeb expression in the vasculature (mice n=10). Representative images of glomerular, arterial (scale bars: 10 µm) and interstitial vessels (scale bar: 50 µm) of kidney (p17) of Tfeb-EGFP mice stained with anti-CD31 (B) and anti-GFP",
    "ncbi_link": "EGFP: 
Tfeb: 21425"
  },
  {
    "caption": "Alterations in the embryonic vasculature in TfebEC-/- mice at E10.5 (mice n=25). Representative images of whole-mount embryos and yolk sacs (i, ii) (scale bars: 0.5 mm). Vessels of the head (iii), ocular (iv) and intrasomitic regions (v) were stained with anti-endomucin Ab (scale bars: 100 µm).",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Alteration of retinal vascular maturation in TfebiEC-/- at p5. Representative images of whole mounts of retina and immunostaining of vascular front and vascular plexus with an anti-iB4 Ab (scale bars: 50 µm). Bar graphs indicate the percent of vascular area versus total area of the retina, the percent of vascular density, the number of branches per field, vessel diameter, the number of filopodia per field and the length of filopodia (mice n=10, mean±SEM; ***p< 0.0001 versus control mice by Student's t-test).",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Alteration of the glomerular ultrastructure in TfebiEC-/- mice at p17 (mice n=5). Representative transmission electron micrographs of renal tissue. Magnification: i) x6000, ii) x20000), iii-iv) x10000, v-vi) x25000; scale bars: 1µm). Asterisks indicate the accumulation of extracellular matrix in mesangium; white and black triangles indicate the fusion of podocyte foot processes and the lack of endothelial fenestrae, respectively.",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Reduced EC proliferation in the retina (p5) of in TfebiEC-/- mice. Representative images of vessels of the vascular front and vascular plexus in the retina of control and TfebiEC-/- mice stained with anti-iB4 and Ki-67 antibodies (scale bars: 50 µm). Bar graph indicates the percentage of EC Ki-67+ nuclei versus total nuclei co-localized with iB4+ vessels",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Reduced EC proliferation in the kidney (p17) of in TfebiEC-/- mice. (B) Representative images of vessels of the kidney in control and TfebiEC-/- mice stained with anti-CD31 and Ki-67 antibodies (scale bars: 50 µm). Bar graph indicates the percent of EC Ki-67+ nuclei versus total nuclei co-localized with CD31+ vessels (mice n=6, mean±SEM; **p<0.001 versus control mice by Student's t-test). Podocin staining is shown to glomerular localization.",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "TFEB silencing reduced EC proliferation. Representative graph of scr-shRNA and sh-TFEB ECs treated for 24 hours with FCS (20%) or VEGF-A (30 ng/ml). (C) DNA incorporation of EdU was detected by flow cytometry. The percentage of proliferating cells is indicated (n=4, mean±SEM; ***p<0.0001 versus scr-shRNA ECs by Student's t-test).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "TFEB silencing reduced EC proliferation. Representative graph of scr-shRNA and sh-TFEB ECs treated for 24 hours with FCS (20%) or VEGF-A (30 ng/ml). DNA content was determined by propidium iodide staining and assessed by fluorescences-activated cell sorter analysis (representative experiment out of 4 with similar results).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "TFEB silencing reduced human EC morphogenesis. Representative images of tube-like-structure of scr-shRNA and sh-TFEB human ECs stained with phalloidin-555. Bar graph indicates the percentage of phalloidin+ area in sh-TFEB and scr-shRNA ECs (scale bars: 0.25 mm; n=6, mean±SEM; ***p<0.0001 versus scr-shRNA by Student's t-test).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Heatmap showing unsupervised hierarchical clustering of human differentially expressed genes between human scr-shRNA and sh-TFEB ECs. Red: up-regulated genes; green: down-regulated genes.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "qPCR Data are expressed as relative fold-change compared with the expression in scr-shRNA cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: "
  },
  {
    "caption": "immunoblots showing the differentially expressed cell cycle related genes between scr-shRNA and sh-TFEB ECs. Immunoblots of total lysates from scr-shRNA and sh-TFEB ECs probed with specific Abs. The bar graph shows the densitometric analysis expressed as the ratio between the cell cycle genes and α-tubulin",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Modulation of cell cycle genes expression in the lung ECs derived from control and TfebiEC-/- mice. Data are expressed as relative fold-change compared with the expression in ECs of control mice after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
Tfeb: 21425"
  },
  {
    "caption": "Analysis of TFEB binding and modulation of the CDK4 promoter in human ECs. ChIP was performed using digested chromatin from control ECs and TFEBS142A ECs incubated with IgG (indicated in the bar graph as "+IgG") or with Ab anti-TFEB (indicated in the bar graph as "+Ab anti-TFEB"), followed by qPCR for CDK4. Bar graph shows the percent enrichment (n=3, mean±SD).",
    "ncbi_link": "CDK4: 1019
TFEB: 7942"
  },
  {
    "caption": "Analysis of TFEB binding and modulation of the CDK4 promoter in human ECs. Analysis of TFEB modulation of CDK4 promoter in human ECs. Bar graph shows the relative luciferase activity % evaluated in control and TFEBS142A human ECs after transfection of CDK4 full promoter and CDK4 promoter deleted of TFEB binding site",
    "ncbi_link": "CDK4: 1019
TFEB: 7942"
  },
  {
    "caption": "Modulation of Rb protein in sh-TFEB ECs. Immunoblots of total lysates from scr-shRNA and sh-TFEB ECs probed with phospho-Rb and total Rb Abs. The bar graph shows the densitometric analysis of the immunoblotting expressed as % of sh-TFEB vs scr-shRNA and the ratio between phospho-Rb and total Rb in the different conditions",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Increase of Vegfr2 expression in the vasculature of TfebEC-/- mice. Representative immunostaining images of TfebEC-/- embryonic vessels (E10.5) stained with anti-endomucin and anti-Vegfr2 Abs (scale bars: 50 µm). Bar graph indicates the Vegfr2 mean intensity only in endomucin+ vessel areas (embryos n=6, mean±SEM; ***p< 0.0001 versus control embryos by Student's t-test).",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Increase of Vegfr2 expression in the vasculature of TfebiEC-/- mice. Representative immunostaining images (i) and detail (ii) of the vascular front and vascular plexus of the retina (p5) of control and TfebiEC-/- mice with anti-iB4 and anti-Vegfr2 Abs (scale bars: 50 µm). Bar graph indicates the Vegfr2 mean intensity only in iB4+ vessel areas",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Increase of Vegfr2 expression in the vasculature of TfebiEC-/- mice. Representative immunostaining images of the glomerulus (p17) of control and TfebiEC-/- mice with anti-podocin, anti-CD31 and anti-Vegfr2 Abs (scale bars: 50 µm). Bar graphs indicate the Vegfr2 mean intensity in CD31+ vessel areas",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB. qPCR of VEGFR2 in lung ECs obtained from control and TfebiEC-/- mice (D) Data are expressed as relative fold-change compared with the expression in control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
VEGFR2: 16542
TFEB: 21425
Tfeb: 21425"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB. qPCR of VEGFR2 in lung ECs obtained from control and in human sh-TFEB Data are expressed as relative fold-change compared with the expression in control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
VEGFR2: 3791
TFEB: 7942"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB. Immunoblots of total lysates from scr-shRNA and sh-TFEB ECs probed with anti-VEGFR2 and α-tubulin Abs. The bar graph shows the densitometric analysis expressed as the ratio between VEGFR2 and α-tubulin",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Analysis of TFEB binding to the VEGFR2 promoter in human ECs. ChIP was performed using digested chromatin from human control ECs and TFEBS142A ECs incubated with IgG (indicated in the bar graph as "+IgG") or with Ab anti-TFEB (indicated in the bar graph as "+Ab anti-TFEB"), followed by qPCR for VEGFR2.",
    "ncbi_link": "VEGFR2: 3791
TFEB: 7942"
  },
  {
    "caption": "Silenced TFEB alters the localization of VEGFR2. FACS analysis of surface VEGFR2 expression on human scr-shRNA and sh-TFEB ECs. Bar graph shows the ratio between total and PM VEGFR2",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Silenced TFEB alters the localization of VEGFR2. Representative TIRF and epifluorescence images of human scr-shRNA and sh-TFEB ECs after staining with anti-VEGFR2 Ab (scale bars: 10 µm). Bar graphs show the ratio of VEGFR2 analyzed in epifluorescence and TIRF mode analyzed by TIRF",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Silenced TFEB alters the localization and the phosphorylation state of VEGFR2 and its signal transduction. Representative immunoblot of PM biotinylated portion and total cell lysates of scr-shRNA and sh-TFEB ECs after VEGF-A stimulation (30 ng/ml). Blots of total or PM cell lysates were probed with anti-VEGFR2. Blots of total cell lysates were probed with anti-p-Y1175-VEGFR2, anti-PLCγ, p-PLCγ, anti-ERK-1/2, anti-pERK1/2, anti-p-Src, anti-Src, anti CD31 and α-tubulin Abs. The bar graphs (i,ii) show densitometric analysis of stimulated versus unstimulated scr-shRNA and sh-TFEB ECs expressed as: (i) % of VEGFR2 on PM fraction (n=3, mean±SEM; ANOVA p<0.02; **p<0.001 versus scr-shRNA by Bonferroni post-test), (ii) % of VEGFR2 total",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Regulaton of autophagy and lysosome pathway by TFEB silencing. qPCR showing the differentially expressed autophagy and lysosome related genes between human scr-shRNA and sh-TFEB ECs. Data are expressed as relative fold-change compared with the expression in control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
TFEB: 7942"
  },
  {
    "caption": "Regulaton of autophagy and lysosome pathway by TFEB silencing. immunoblots showing the differentially expressed autophagy and lysosome related genes between human scr-shRNA and sh-TFEB ECs. Immunoblots of total lysates from human scr-shRNA and sh-TFEB ECs probed with anti-ULK-1, anti-ATG9, anti-LC3-I/II, anti-LAMP-1 and α-tubulin Abs. The bar graph shows the densitometric analysis expressed as the ratio between scr-shRNA and sh-TFEB ECs",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "TFEB silencing inhibits VEGFR2 internalization. Bar graphs of VEGFR2 internalization expressed as the percent of internalized VEGFR2 versus PM VEGFR2 after VEGF-A stimulation",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Analysis of TFEB binding and modulation of the MYO1C promoter in human ECs. ChIP was performed using digested chromatin from control ECs and TFEBS142A ECs incubated with IgG (indicated in the bar graph as "+IgG") or with Ab anti-TFEB (indicated in the bar graph as "+Ab anti-TFEB"), followed by qPCR for MYO1C. Bar graph shows the percent enrichment (n=3, mean±SD).",
    "ncbi_link": "MYO1C: 4641
TFEB: 7942"
  },
  {
    "caption": "Analysis of TFEB binding and modulation of the MYO1C promoter in human ECs. qPCR of MYO1C expression in scr-shRNA, sh-TFEB, sh-MYO1C and sh-TFEB+sh-MYO1C ECs. Data are expressed as relative fold change compared with the expression in scr-shRNA ECs after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
MYO1C: 4641
TFEB: 7942"
  },
  {
    "caption": "MYO1C silencing reverses the effect of TFEB silencing on the up-regulation of PM VEGFR2. Analyses were performed on human ECs carrying appropriate scr-shRNA or sh-TFEB in the presence or absence of sh-MYO1C. Representative western blot of MYOC1, total and PM biotinylated VEGFR2 (representative experiment out of 4 with similar results).",
    "ncbi_link": "MYO1C: 4641
TFEB: 7942"
  },
  {
    "caption": "Representative immunostaining images of the vascular plexus of the retina (p5) (E) and glomerulus (p17)(F) of control and TfebiEC-/- mice with anti-CD31 and anti-MYO1C Abs (scale bars: 50 µm). Bar graphs indicate the Myo1C mean intensity only in vessel areas CD31+",
    "ncbi_link": "Tfeb: 21425"
  },
  {
    "caption": "Representative TIRF and epifluorescence images of VEGFR2 in scr-shRNA, sh-TFEB, sh-MYO1C and sh-TFEB+sh-MYO1C human ECs (scale bars: 10 µm). Bar graph shows the ratio between PM and total VEGFR2",
    "ncbi_link": "MYO1C: 4641
TFEB: 7942"
  },
  {
    "caption": "Analysis of TFEB binding to DLEU2 and SMC4 promoters in human ECs. ChIP was performed using digested chromatin from control ECs and TFEBS142A ECs incubated with IgG (indicated in the bar graph as "+IgG") or with Ab anti-TFEB (indicated in the bar graph as "+Ab anti-TFEB"), followed by qPCR for DLEU2 and SMC4.",
    "ncbi_link": "DLEU2: 8847
SMC4: 10051
TFEB: 7942"
  },
  {
    "caption": "DLEU2 expression is regulated by TFEB. qPCR of DLEU2 in human scr-shRNA, sh-TFEB or control and TFEBS142A ECs (left panel) and lung ECs obtained from control and TfebiEC-/- mice (right panel). Data are expressed as relative fold-change compared with the expression in scr-shRNA and control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
DLEU2: 8847
TFEB: 7942
Tfeb: 21425"
  },
  {
    "caption": "Human miR-15a-5p and miR-16-5p are regulated by TFEB. qPCR of miR-15a-5p (left panel) and miR-16-5p (right panel) in sh-TFEB or TFEBS142A ECs. Data are expressed as relative fold-change compared with the expression in scr-shRNA and control cells after normalization to the housekeeping gene RNU44",
    "ncbi_link": "RNU44: 
miR-15a-5p: 8847
miR-16-5p: 406950
TFEB: 7942"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB through a miR-dependent mechanism. qPCR of VEGFR2 in human scr-shRNA and sh-TFEB ECs and in control treated with a specific miR-control, miR-15a-5p and miR-16-5p mimics Data are expressed as relative fold-change compared with the expression in control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
miR-15a-5p: 8847
VEGFR2: 3791
miR-16-5p: 406950
TFEB: 7942"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB through a miR-dependent mechanism. VEGFR2 in human scr-shRNA and sh-TFEB ECs and in control treated with a specific miR-control, miR-15a-5p and miR-16-5p mimics Representative western blot of VEGFR2 expression under the same experimental conditions previously reported. The bar graph shows the densitometric analysis expressed as the ratio between VEGFR2 and α-tubulin",
    "ncbi_link": "miR-15a-5p: 8847
miR-16-5p: 406950
TFEB: 7942"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB through a miR-dependent mechanism. qPCR of VEGFR2 in control and TFEBS142A ECs treated with a specific miR-control, miR-15a-5p and miR-16-5p inhibitors. Data are expressed as relative fold-change compared with the expression in control cells after normalization to the housekeeping gene TBP",
    "ncbi_link": "TBP: 
miR-15a-5p: 8847
VEGFR2: 3791
miR-16-5p: 406950
TFEB: 7942"
  },
  {
    "caption": "VEGFR2 expression is regulated by TFEB through a miR-dependent mechanism. VEGFR2 in control and TFEBS142A ECs treated with a specific miR-control, miR-15a-5p and miR-16-5p inhibitors. Representative western blot of VEGFR2 expression under the same experimental conditions previously reported. The bar graph shows the densitometric analysis expressed as the ratio between VEGFR2 and α-tubulin",
    "ncbi_link": "miR-15a-5p: 8847
miR-16-5p: 406950
TFEB: 7942"
  },
  {
    "caption": "B-D. Mice were analyzed by Kaplan-Meier survival plot (B), the percentage of body weight (C), and the clinical scores (D) of WT and GPx8-/- mice with colitis induced by 4% DSS for 6 days (n = 10 per group). Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "Gut microbiome was shaped by Gpx8 deficiency under standard housing conditions. Bray Curtis dissimilarity of fecal microbiota were measured by bacterial 16S RNA sequencing (n = 5 per group) and are presented by a heat map, (I), and principal coordinates analysis, (J).",
    "ncbi_link": "Gpx8: 69590"
  },
  {
    "caption": "Gut microbiome was shaped by Gpx8 deficiency under standard housing conditions. (K) α-diversity indicated bacteria species in each mouse depicted by richness (total operational taxonomic units, OTUs), the Chao1 richness estimator (Chao1), and the abundance-based coverage estimator (ACE) metrics. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "Gpx8: 69590"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). (C) The percentage of body weight. (D) The clinical scores of mice. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (E) Statistical analysis of colon length. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (F) Images and semiquantitative scoring of hematoxylin and eosin staining colon sections. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (G) Colon sections stained with anti-F4/80. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "After undergoing macrophage depletion, C57BL/6 mice received macrophages derived from WT (WT BMDMs) or GPx8-/- mice (GPx8-/- BMDMs) were under DSS-induced colitis (n = 6-9 per group). D) Colon samples from BMDMs transplanted mice were collected on day 7 under colitis model. (H) Production of IL-1β, IL-6 and IL-18 in colon tissue lysates. Data information: Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's one‐tailed t‐test). ",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "A. Canonical NLRP3 inflammasome activation was not altered by GPx8 deficiency. BMDMs were primed for 6 h with 0.5 μg/ml LPS and then transfected with LPS (TF LPS) for 8 h, stimulated with ATP (5 mM) for 3 h, MSU (150 μg/mL) for 8 h, or nigericin (5 μM) for 3 h. Activation of inflammasome was demonstrated by secreted IL-1β. Data information: data are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats. P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "B. GPx8 deficiency enhanced noncanonical inflammasome activation. Activation of the noncanonical inflammasome by different amounts of cytoplasmic LPS was verified by IL-1β (left panel) and LDH release (right panel). Data information: data are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats. P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "C. Upregulation of noncanonical inflammasome activation by GPx8 deficiency occurred independently of TLRs. BMDMs were primed for 6 h with 1 μg/ml poly(I:C) and then transfected with LPS for 8 h. Data information: data are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats. P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "Over-activation of noncanonical inflammasome induced by GPx8 deficiency in BMDMs can be rescued by ectopically-expressing human GPx8 (hGPx8). (D) Activation of noncanonical inflammasome in BMDMs with empty vector (EV) or hGPx8 was verified by IL-1β (left panel) and LDH release (right panel). Data information: data are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats. P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590
GPx8: 493869
hGPx8: 493869"
  },
  {
    "caption": "Over-activation of noncanonical inflammasome induced by GPx8 deficiency in BMDMs can be rescued by ectopically-expressing human GPx8 (hGPx8). (E) Expression of hGPx8 mRNA in BMDMs was confirmed by quantitative reverse transcriptase PCR. Data information: data are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats.",
    "ncbi_link": "GPx8: 69590
GPx8: 493869
hGPx8: 493869"
  },
  {
    "caption": "F. GPx8 deficiency enhanced caspase-11 cleavage and activation. Levels of processed caspase-1 and -11 in the supernatants (Sup) and full-length caspase-1, -11 and GAPDH in the cell lysates (Cell ext) were determined by immunoblotting. Fold changes of protein expression were normalized with internal controls and are indicated below the blots.",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "G. RNA expression of caspase-11 was not altered by GPx8 deficiency. Caspase-11 RNA expression of BMDMs isolated from GPx8-/- mice was measured after LPS priming. Data information: ata are representative of at least 3 independent experiments and presented as the mean ± SD, n=4-5, technical repeats.",
    "ncbi_link": "caspase-11: 12363
Caspase-11: 12363
GPx8: 69590"
  },
  {
    "caption": "H. GPx8 deficiency enhanced noncanonical inflammasome activation and pyroptosis in vivo. Colon samples from 5 WT or GPx8-/- mice treated with DSS for 5 days were collected on day 7. Levels of full-length and processed caspase-1, -11 and gasdermin D (GSDMD) in tissue lysates were individually analyzed by immunoblots.",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "GPx8-/- mice were more susceptible than WT mice to endotoxic shock by activation of the noncanonical inflammasome. (I) Survival of mice primed with ultra pure LPS (E. coli O55:B5, 400 μg/kg) and re-challenged 6 h later with LPS (40 mg/kg) (n = 8 per group).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "GPx8-/- mice were more susceptible than WT mice to endotoxic shock by activation of the noncanonical inflammasome. (J) Survival of mice primed with poly(I:C) (LMW 1 mg/kg) and re-challenged 6 h later with LPS (10 mg/kg) (n = 9 per group).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "GPx8-/- mice were more susceptible than WT mice to endotoxic shock by activation of the noncanonical inflammasome. (K) IL-1β production levels in mice sera were measured 2 h after being primed with poly(I:C) (LMW 1 mg/kg) and re-challenged 6 h later with LPS (1 mg/kg) (n = 8-9 per group). In (K), data are presented as the mean ± SEM. NS, no significance. P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 69590"
  },
  {
    "caption": "A. Interaction of GPx8 with human caspase-4 (Casp4) or mouse caspase-11 (Casp11) was confirmed by co-IP assays. 293T cells were co-transfected with vectors expressing FLAG tagged Casp4 or Casp11, in addition to GPx8 expressing vectors. Cell lysate containing Casp4- or Casp11-FLAG proteins was immunoprecipitated by anti-FLAG Ab and subsequently analyzed by Western blots using anti-GPx8 and anti-FLAG Ab (left panel). GPx8 and its interacting proteins were precipitated by anti-GPx8 Ab and analyzed by the indicated Abs (right panel).",
    "ncbi_link": "FLAG: 
GPx8: 
Casp11: 12363
Casp4: 837"
  },
  {
    "caption": "C. Interaction between GPx8 and caspase-4 in THP-1 cells in the presence or absence of priming LPS was demonstrated by the in situ proximity ligation assay (PLA) (red dots, labeled by arrowheads). GPx8-Myc stably expressing THP-1 were used to detect the interaction between GPx8-Myc and endogenous caspase-4. Untreated cells (Ctrl) or cells primed with LPS (primed LPS) were incubated with anti-Myc and anti-caspase-4 Abs, according to the manufacturer's instructions, and the nucleus was stained with DAPI (blue). Results were quantified by counting at least 5 different fields with an average of 300 cells. Reactions without primary Abs were used as the control for the PLA assay (PLA Ctrl). Data information: All data are representative of at least 3 independent experiments. *P < 0.05; **P < 0.01; *** P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 
Myc: "
  },
  {
    "caption": "293T cells were co-transfected with vectors expressing FLAG tagged caspase-4 (WT or C258S) in addition to GPx8 expressing vectors. Cell lysate was immunoprecipitated by anti-FLAG Ab and subsequently analyzed by Western blots using anti-GPx8 or anti-FLAG Ab. (D) Complexes of GPx8 and caspase-4 were demonstrated by co-IP assays. Cysteine-dependent covalent interactions of GPx8 and caspase-4 (C258S) were analyzed under non-reducing and reducing conditions. Disulfide-linked complexes of Gpx8 and caspase-4 are indicated.",
    "ncbi_link": "FLAG: 
GPx8: 
caspase-4: 12363"
  },
  {
    "caption": "293T cells were co-transfected with vectors expressing FLAG tagged caspase-4 (WT or C258S) in addition to GPx8 expressing vectors. Cell lysate was immunoprecipitated by anti-FLAG Ab and subsequently analyzed by Western blots using anti-GPx8 or anti-FLAG Ab. (E) Interactions of GPx8 and caspase-4 in response to H2O2 treatment were demonstrated by co-IP assays of lysates prepared from 293T cells treated with H2O2 (200 μM).",
    "ncbi_link": "FLAG: 
GPx8: 
caspase-4: 12363"
  },
  {
    "caption": "293T cells were co-transfected with vectors expressing FLAG tagged caspase-4 (WT or C258S) in addition to GPx8 expressing vectors. Cell lysate was immunoprecipitated by anti-FLAG Ab and subsequently analyzed by Western blots using anti-GPx8 or anti-FLAG Ab. (F) C79S, C108S, and C2S2 mutants of GPx8 abolished most of the binding to caspase-4 by co-IP assays.",
    "ncbi_link": "FLAG: 
GPx8: 
caspase-4: 12363"
  },
  {
    "caption": "C79 of GPx8 was essential for its inhibitory effect on noncanonical inflammasome activation. THP-1 cells stably expressing empty vector (EV), WT, or mutant GPx8 proteins were confirmed by immunoblotting (G).",
    "ncbi_link": "GPx8: "
  },
  {
    "caption": "C79 of GPx8 was essential for its inhibitory effect on noncanonical inflammasome activation. (H and I) Cells were treated with 12-O-tetradecanoylphorbol 13-actate (PMA) (0.1 μM) and differentiated for 3 days then primed and transfected with LPS. Activation of the noncanonical inflammasome by different amounts of cytoplasmic LPS was verified by IL-1β (H) and LDH release (I). Data information: All data are representative of at least 3 independent experiments. In H and I, data are presented as the mean ± SD, n=4, technical repeats. *P < 0.05; **P < 0.01; *** P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: "
  },
  {
    "caption": "A. Casp4C118S mutant partially abolished the covalent disulfide-link with GPx8. Interacting GPx8 were co-immunoprecipitated with FLAG-tagged caspase-4 (WT, C118S, C329S mutants) and analyzed under reducing (+DTT) or non-reducing (-DTT) conditions. Disulfide-linked complexes of GPx8 and caspase-4 are indicated. Fold change of complexes was normalized with internal controls and indicated below blots.",
    "ncbi_link": "FLAG: 
Casp4: 12363
caspase-4: 12363"
  },
  {
    "caption": "C118 of caspase-4 was required for the GPx8-mediated inhibitory effect. THP-1 cells stably expressing empty vector (EV), FLAG-tagged caspase-4 (WT, C258S, C118S mutants), or GPx8 (WT and C79S mutants) were confirmed by immunoblotting (B). Data information: All data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "FLAG: 
GPx8: 
caspase-4: 12363"
  },
  {
    "caption": "C118 of caspase-4 was required for the GPx8-mediated inhibitory effect. (C-D) Casp4C118S completely abolished the inhibition of noncanonical inflammasome signaling in response to intracellular LPS. THP-1 cells were differentiated, primed, and transfected with LPS. Activation of the noncanonical inflammasome by different quantities of cytoplasmic LPS is confirmed by the production of IL-1β (C) and LDH (D). In C and D, data are presented as the mean ± SD, n=4, technical repeats. ***P < 0.001 (Student's two‐tailed t‐test).",
    "ncbi_link": "GPx8: 
Casp4: 12363
caspase-4: 12363"
  },
  {
    "caption": "(b) PC12 cells transfected with either 60Q or 60Q-HSC70bm. The presence of two HSC70bm motifs in 60Q-HSC70bm reduced the number of inclusions as compared to 60Q (scale bar, 20 μm). (c) Quantification of the PC12 cells with inclusions 24 h after transfection with either 60Q or 60Q-HSC70bm. 10 mM 3-methyladenine (3-MA), 10 μM pepstatin A and 10 μM leupeptin were added to inhibit macroautophagy, the proteases, cathepsins D and E, and cathepsin A, respectively. Bars in c represent relative mean values ± s.e.m. from four independent experiments, with levels of aggregation observed for 60Q normalized to a value of 1. Quantifications were performed by ArrayScan.",
    "ncbi_link": "HSC70bm: 6622"
  },
  {
    "caption": "(b) Confocal images of the 150Q Neuro2a cells transfected with R, RH, RS, RHS, RQ and RHQ. Molecules containing QBP1 co-localized with the tNHTT-150Q-EGFP inclusions (bar, 5 μm). Cells with inclusions were chosen to illustrate the co-localization of QBP1-containing molecules with tNHTT-150Q-EGFP.",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(c) The expression of RQ and RHQ in 150Q Neuro2a cells decreased the accumulation of insoluble tNHTT-150Q-EGFP on the gel top. Note the shift of tNHTT-150Q-EGFP from an insoluble to a soluble form when RQ was co-expressed. The levels of tNHTT-16Q-EGFP were not affected. Full-length western blots are presented in Supplementary Figure 13.",
    "ncbi_link": "150Q: 3064
HTT: 3064"
  },
  {
    "caption": "(d) RHQ reduced the levels of aggregated and soluble forms of tNHTT-150Q-EGFP by 81.8% and 33.6%, respectively. WB, western blot. (e) Quantification of tNHTT-16Q-EGFP protein levels.",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(a,b) Constructs identical to those described in Figure 2a, but lacking mRFP (representations of S, HS, Q, HQ are shown in Supplementary Fig. 3a) were co-transfected with tNHTT-16Q-EGFP (a) and tNHTT-150Q-EGFP (b) constructs into Neuro2a cells (bar, 4 μm).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(c) Dot blot analysis of the lumenal fraction of purified lysosomes from Neuro2a cells co-transfected with tNHTT-60Q-EGFP and R, RS, RHS, RQ or RHQ. PNS, post-nuclear supernatant.",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(d) Quantification of HTT translocation into lysosomes. Levels of HTT detected by EM48 (anti-huntingtin antibody) were normalized to levels of β-tubulin (in PNS) and levels of cathepsin D (in lysosomes).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(e) Compound images generated by ArrayScan illustrating inclusion formation in 150Q Neuro2a cells transfected with R, RS, RHS, RQ and RHQ and shRNA specific for HSC70 and/or Lamp2a. (blue, Hoechst 33258; green, tNHTT-150Q-EGFP; red, tested molecule).",
    "ncbi_link": "HSC70: 15481"
  },
  {
    "caption": "(f) RNAi of HSC70, Lamp2a or both alleviated the inhibitory effect of RHQ on the formation of inclusions containing tNHTT-150Q-EGFP inclusions.",
    "ncbi_link": "HSC70: 15481
Lamp2a: 16784"
  },
  {
    "caption": "(g) Western blot analysis of soluble polyQ protein in 150Q Neuro2a cells transfected with tested constructs and shRNA for HSC70 and/or Lamp2a. Full-length western blots are presented in Supplementary Figure 13.",
    "ncbi_link": "HSC70: 15481
Lamp2a: 16784"
  },
  {
    "caption": "(h) Silencing of HSC70, Lamp2a or both alleviated the inhibitory effect of RHQ on levels of soluble tNHTT-150Q-EGFP. Bars in d and f represent mean values ± s.e.m. from three independent experiments. Bars in h represent relative mean values ± s.e.m. from three independent experiments. For h, values for the R construct were arbitrarily set to 1.",
    "ncbi_link": "HSC70: 15481
Lamp2a: 16784"
  },
  {
    "caption": "(c) Western blot analysis of HTT aggregation (gel top, EM48 antibody), soluble HTT (1C2 antibody), and higher molecular polyQ complexes by agarose gel electrophoresis for resolving aggregates (AGERA). Full-length western blots are presented in Supplementary Figure 13. (d) Quantification of the gel top-detected aggregation (*, P = 0.093; **, P = 0.0027; ***, P = 0.0045). (e) Quantification of soluble HTT-polyQ (*, P = 0.034; **, P = 0.00003; ***, P = 0.0001).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(B) Representative live-cell fluorescent images of HeLa cells co-transfected with EGFP-TECPR1 and LAMP1-mCherry and treated with 1 mM LLOMe for the indicated time. Scale bar = 10 µM.",
    "ncbi_link": "EGFP: 
mCherry: 
LAMP1: 3916
TECPR1: 25851"
  },
  {
    "caption": "(D) Representative live-cell fluorescent images of HeLa cells co-transfected with EGFP-TECPR1 and LAMP1-mCherry and treated as indicated. Scale bars = 10 µM. (E) Quantification of the fold change in EGFP-TECPR1 lysosomal fluorescence from D. Grey points represent individual cells from three independent experiments. Red points represent the means of individual experiments (n > 25 cells per experiment). Bars represent the mean ± SD from the three experiments. Significance was determined from biological replicates using a one-way ANOVA with Tukey's multiple comparisons tests. ** p = <0.005, **** p < 0.0001, ns = not significant.",
    "ncbi_link": "EGFP: 
mCherry: 
LAMP1: 3916
TECPR1: 25851"
  },
  {
    "caption": "(B) Representative live-cell fluorescent images of HeLa cells co-transfected with the indicated EGFP-TECPR1 deletion mutant and LAMP1-mCherry before and after treatment with 1 mM LLOMe. Scale bars = 10 µM. To the right is the corresponding quantification of the fold change in EGFP-TECPR1 lysosomal fluorescence intensity after a 15-minute treatment with vehicle or 1 mM LLOMe. Grey points represent individual cells from three independent experiments.",
    "ncbi_link": "EGFP: 
mCherry: 
LAMP1: 3916
TECPR1: 25851"
  },
  {
    "caption": "(A,B) Representative live-cell fluorescent images of HeLa cells co-transfected with EGFP-TECPR1 and mCherry-Gal3 and treated with 1 mM LLOMe for the indicated time. Arrowheads in B indicate the appearance of TECPR1 (green arrow) and Gal3 (magenta arrow). Scale bars = 10 µM for A and 1 µM for B. (C) Quantification of TECPR1 and Gal3 recruitment to damaged lysosomes. Data are presented as mean ± SD from 5 independent experiments (each experiment represents a single cell with at least 3 individual lysosomes quantified).",
    "ncbi_link": "EGFP: 
mCherry: 
Gal3: 8484
TECPR1: 25851"
  },
  {
    "caption": "(D) Representative confocal image of a HeLa cell transfected with EGFP-TECPR1, treated with LLOMe for 5 minutes, and immunostained for CHMP2A and LAMP1. Scale bars = 10 µm for whole image and 1 µm for insets. Fluorescence intensity profiles of the indicated channels across the dotted lines are shown in the lower subpanel. (E) Representative confocal images of a HeLa cells transfected with EGFP-TECPR1 and TagBFP-TMEM192 (a lysosomal/late endosomal protein), treated with 1 mM LLOMe for the indicated time, and immunostained for ALIX and Gal3. Scale bars = 10 µm.",
    "ncbi_link": "EGFP: 
TECPR1: 25851"
  },
  {
    "caption": "(A) Western blot analysis of LC3 lipidation status in wild type (WT), FIP200 KO and ATG16L1 KO HeLa cells treated with the indicated concentrations of LLOMe for 30 minutes.",
    "ncbi_link": "ATG16L1: 55054
FIP200: 9821"
  },
  {
    "caption": "(B) Quantification of LC3-II levels in HEK, HeLa and MEF WT and ATG16L1-deficient cell lines treated with and without 1 mM LLOMe for 30 minutes. Bars show mean ± SD from three biologically independent experiments represented as data points. Significance was determined from biological replicates using a Student's t tests. *p = 0.0177, ** p = 0.0082, *** p = 0.0001.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(C) Western blot analysis of LC3 lipidation status in WT, ATG7 KO and ATG16L1 KO HeLa cells (top) and WT, ATG5-/- and ATG16L1Δ/Δ MEFs (bottom) treated with the indicated concentration of LLOMe for 30 minutes.",
    "ncbi_link": "ATG16L1: 55054
ATG16L1: 77040
ATG5: 11793
ATG7: 10533"
  },
  {
    "caption": "(F) Western blot analysis of lyso-IP samples collected from HeLa ATG16KO cells treated with or without 1 mM LLOMe for 30 minutes. Bars show mean ± SD from three biologically independent experiments represented as data points.",
    "ncbi_link": "ATG16: 55054"
  },
  {
    "caption": "(G) Representative live-cell fluorescent images of HeLa cells co-transfected with TagBFP-TMEM192, EGFP-ATG5 and mCherry-TECPR1, before and after a 15-minute treatment with 1 mM LLOMe. Scale bars = 10 µm for whole images and 2 µm for zoom. To the right is the corresponding quantification of the fold change in ATG5/TECPR1 lysosomal fluorescence intensity after a 15-minute treatment with vehicle or 1 mM LLOMe. Grey points represent individual cells from three independent experiments. Green/magenta points represent the means of individual experiments (n > 25 cells per experiment).",
    "ncbi_link": "EGFP: 
mCherry: 
TagBFP: 
ATG5: 9474
TECPR1: 25851
TMEM192: 201931"
  },
  {
    "caption": "(H) Western blot analysis of LC3 lipidation status in HEK TECPR1/ATG16L1 KO cells treated with 1 mMLLOMe for 30 minutes. To the right is the corresponding quantification of LC3-II protein levels. Bars show mean ± SD from three or four biologically independent experiments which are represented as data points.",
    "ncbi_link": "ATG16L1: 55054
TECPR1: 25851"
  },
  {
    "caption": "(A) Subjective assessment of hair depigmentation (score 0-5, with 0 = completely black and 5 = completely white) at 2 doses of either CNP520 or the BACE-1/-2 inhibitor NB-360 (mean ± SEM, n=8/group), statistical comparisons were made for every scoring day, versus vehicle using Kruskal-Wallis with Dunn's post-hoc test.",
    "ncbi_link": "BACE-1: 23821"
  },
  {
    "caption": "(A) Mouse forebrain Aβ40 levels in homozygous male and female APOE4-TR mice with and without CNP520 treatment, 4 hours after dosing, shown are mean ± SEM, n = 6/group.",
    "ncbi_link": "APOE4: 348"
  },
  {
    "caption": "(B) Distribution of APOE4 genotypes in the Phase IIa study, vs their baseline Aβ42/40 ratios. The dashed line at Aβ42/40 ratio of 0.09 represents a cutoff, which separates a normal ratio from an abnormally low ratio.",
    "ncbi_link": "APOE4: 348"
  },
  {
    "caption": "(C) Comparison of CSF Aβ40 reduction in APOE4 non-carriers and APOE4 carriers.",
    "ncbi_link": "APOE4: 348"
  },
  {
    "caption": "(F) Change of Aβ42/40 ratio for all participants with Aβ42/40 ≤ 0.09 at baseline; bars represent mean ± SD. Full circles: APOE4 carrier, open circles: APOE4 non-carrier.",
    "ncbi_link": "APOE4: 348"
  },
  {
    "caption": "Immunofluorescence staining of RANKL during in vitro adipogenesis of BMSCs from AdipoqCre; ranklfl/fl mice (Rankl-/-) and ranklfl/fl mice (Rankl+/+). Scale bar=50 μm.",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
rankl: 21943
Rankl: 21943"
  },
  {
    "caption": "Micro-CT and statistical analyses of BMD, BV/TV, Tb.N and Tb.Sp in trabecular bone from AdipoqCre; ranklfl/fl (Rankl-/-) and ranklfl/fl (Rankl+/+) mice at 4 weeks, 8 weeks and 16 weeks (n=5 independent biological replicates). Scale bar=1 mm. Data were compared using an unpaired t-test (** indicates P < 0.01), error bars are standard deviations.",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
rankl: 21943
Rankl: 21943"
  },
  {
    "caption": "Representative images of TRAP staining of femur from AdipoqCre; ranklfl/fl (Rankl-/-) and ranklfl/fl (Rankl+/+) mice at 8 weeks. Scale bar=200 μm. Panel a1 and a4 indicate trabecular bone, a2 and a5 stand for growth plate, a3 and a6 denote cortical bone.",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
rankl: 21943
Rankl: 21943"
  },
  {
    "caption": "Immunofluorescence staining of osteocalcin from 8-week-old mice (n=6 mice in Rankl-/- group and 4 mice in Rankl+/+ group). Scale bar=50 μm. TB: trabecular bone. Statistical analyses of Ocn+ cells (n=6 independent microscopic vision fields from random mice samples). Data were compared using an unpaired t‐test (** indicates P < 0.01), error bars are standard deviations.",
    "ncbi_link": "Ocn: 12095
Rankl: 21943"
  },
  {
    "caption": "Calcein staining of trabecular bone at 8 weeks. Scale bar=50 μm. TB: trabecular bone. Images are representative of 6 independent biological replicates in Rankl-/- and 5 replicates in Rankl+/+ group. Mineral apposition rate (MAR) of trabecular bone at 8 weeks.(n=6 mice in Rankl-/- group and 5 mice in Rankl+/+ group). Data were compared using an unpaired t‐test ( ** indicates P < 0.01), error bars are standard deviations.",
    "ncbi_link": "Rankl: 21943"
  },
  {
    "caption": "Serum CTX-1, OCN and bone marrow RANKL levels from Rankl-/- and Rankl+/+ mice at 4 weeks (n=5 and 5), 8 weeks (n=5 and 6) and 16 weeks (n=5 and 5). Data were compared using an unpaired t‐test (* indicates P < 0.05, ** indicates P < 0.01), error bars are standard deviations..",
    "ncbi_link": "Rankl: 21943"
  },
  {
    "caption": "Micro-CT analyses of sham and OVX model of AdipoqCre; ranklfl/fl (Rankl-/-) and ranklfl/fl (Rankl+/+) mice (n=5 independent biological replicates). Scale bar=1 mm. Data were compared using an unpaired t‐test (** indicates P < 0.01), error bars are standard deviations.",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
rankl: 21943
Rankl: 21943"
  },
  {
    "caption": "Three-dimensional CT analyses of BMD, BV/TV, Tb.N, and Tb.Sp in trabecular bone from Vehicle (n=5 independent biological replicates) and ROS (n=6 independent biological replicates) model of AdipoqCre; ranklfl/fl (Rankl-/-) and ranklfl/fl (Rankl+/+) mice. Scale bar=1 mm. Data were compared using an unpaired t‐test (** indicates P < 0.01), error bars are standard deviations.  ",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
rankl: 21943
Rankl: 21943"
  },
  {
    "caption": "D. Analysis of spore viability by yeast tetrad dissection. Diploid strains heterozygous for alleles of Nse6 (wt, 86-C, 177-C and 179-C) were sporulated. Isolated  spores were grown on YPD plates. Viable clones were tested for the marker cassette conferring resistance to G418 (marked by circles in green colours). Dead spores were marked by circles in red colours.",
    "ncbi_link": "Nse6: 856760"
  },
  {
    "caption": "C. Kaplan-Meier Survival plot showing low survival of chd7 mutants after 12 dpf (N=5).",
    "ncbi_link": "chd7: 569471"
  },
  {
    "caption": "E. Acetylated tubulin staining  in 28 hpf controls (left) and mutants (right) showing severely affected outbranching of the trigeminal nerve (Vth cranial nerve). Notably, chd7-/- display reduced branching of the Vth cranial nerve (arrows) and axonal arborisation in the tectal  area. Graphs showing quantitative analyses of percentage (n=5) and mean total length  of peripheral projections (n=6) per zebrafish in controls and mutants (***p<0.001; **p<0.005, Student's t-test).",
    "ncbi_link": "chd7: 569471"
  },
  {
    "caption": "C-H Total number of GABAergic neurons  (GFP+ cells) in (C, D) the optic tectum (OT) and cerebellum (CB) regions of 5 dpf wild-type and chd7 mutant fish (n=16; ****p<0.0001; Student's unpaired t-test), (E, F) the hypothalamus (hyp) region (n=10; *p=0.0182; Student's t-test) and (G, H) the telencephalon (tel) (n=7; *p=0.0347; Student's t-test).",
    "ncbi_link": "chd7: 569471"
  },
  {
    "caption": "A. qPCR analysis of PAQR3 expression in a CHD7-mutation positive patient compared to parental controls set (N=4; ****p<0.0001; Student's t-test). Fold change was calculated according to the 2(−ΔΔCt) method, using HPRT1 and RPS1  as housekeeping genes for normalization. All data were expressed as mean fold change ± SD across replicates, relative to control parents set to 1 (dotted line), N is the number of experimental repeats.",
    "ncbi_link": "RPS1: 
CHD7: 55636
HPRT1: 3251
PAQR3: 152559"
  },
  {
    "caption": "C. ChIP-qPCR assays in LCLs showing decreased occupation of CHD7 on the PAQR3 proximal promoter in a CHD7-mutation positive patient (N=3) compared to parental controls (N=6); *p< 0.05; Student's t-test, All data were expressed as mean fold change ± SD, N is the number of experimental repeats.",
    "ncbi_link": "CHD7: 55636
PAQR3: 152559"
  },
  {
    "caption": "C-D. Overexpression of paqr3b mRNA improve the number  of GABAergic neurons in 3dpf chd7  mutant fish (n=7 for chd7-/- and n=11 for chd7-/- + paqr3b  mRNA; ****p<0.0001; **p<0.05; One-way ANOVA). Of note, the rescue experiment was performed at 3 dpf  given the transient nature of mRNA.",
    "ncbi_link": "chd7: 569471
paqr3b: 560764"
  },
  {
    "caption": "B. Lifespan analyses of chd-7(gk290) mutants (n=339; red) compared to WT (n=444; black). Log-rank test was performed for statistical analyses. ***p < 0.001.",
    "ncbi_link": "chd-7: 172079"
  },
  {
    "caption": "D-F. Example pictures of the GABAergic nervous system cell bodies, commissures, axonal gaps and axonal breaks larger than 50 µm per worm in chd-7(gk290) mutants expressing unc-47p::mCherry.",
    "ncbi_link": "chd-7: 172079"
  },
  {
    "caption": "O. Representative images  of GABAergic neurons and total number of GABAergic neurons (GFP+ cells) in the optic tectum  (OT) and cerebellum (CB) regions of wild-type, chd7 mutant and ephedrine-treated fish (n=9; ****p<0.0001; One-way ANOVA). Treatment with ephedrine ameliorated the number of GABAergic neurons.",
    "ncbi_link": "chd7: 569471"
  },
  {
    "caption": "(A) The hair coats of Sirt7−/− and Sirt7+/+ mice were clipped on P60 in the mid second telogen phase. Images were captured at P60, P120 and P150.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(B) The postnatal day when the hair coat recovered by 25%, 50%, 75% and 100% in shaved Sirt7−/− and Sirt7+/+ mice. n = 6 mice/genotype. Box-and-whisker plots: mid-line, median; box, 25th and 75th percentiles; whiskers, minimum and maximum.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(C) H&E staining of the skin in unshaved Sirt7−/− and Sirt7+/+ mice on P90 and P130.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(D) Representative immunofluorescence images showing Ki67 and p-cadherin (Pcad, labeling HG cells) expression in Sirt7−/− and Sirt7+/+ HFs on P74 and P90. The HF boundary and dermal papilla (DP) is denoted by the dotted and dashed lines, respectively.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(F) Telogen duration in Sirt7−/− and Sirt7+/+ mice. n = 6 mice per genotype. Box-and-whisker plots: mid-line, median; box, 25th and 75th percentiles; whiskers, minimum and maximum.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(G) The hair coats of Sirt7-TG and WT mice were clipped on P45 and images were captured on P56 and P90.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(H) The postnatal day when the hair coat recovered by 25%, 50%, 75% and 100% in shaved Sirt7-TG and WT mice. n = 6 mice per genotype. Box-and-whisker plots: mid-line, median; box, 25th and 75th percentiles; whiskers, minimum and maximum.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(I) Representative immunofluorescence images showing Ki67 and Pcad expression in Sirt7-TG and WT HFs at P60 and P65. The HF boundary and DP is noted by the dotted and dashed lines, respectively.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(K) H&E staining of skin tissues in unshaved Sirt7-TG and WT mice on P65.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(L) Telogen duration in Sirt7-TG and WT mice. n = 6 mice per genotype. Box-and-whisker plots: mid-line, median; box, 25th and 75th percentiles; whiskers, minimum and maximum.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(C) The hair coats of Sirt7f/f and Sirt7f/f;K15-Cre mice were clipped at P60 and images were captured on P60, P125 and P150.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Sirt7: 209011"
  },
  {
    "caption": "(D) The postnatal day of hair coat recovery by 25%, 50% 75% and 100% in shaved Sirt7f/f and Sirt7f/f;K15-Cre mice. n = 6 mice per genotype. Box-and-whisker plots: mid-line, median; box, 25th and 75th percentiles; whiskers, minimum and maximum.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Sirt7: 209011"
  },
  {
    "caption": "(E) H&E staining of the skin in Sirt7f/f and Sirt7f/f;K15-Cre mice at P100.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Sirt7: 209011"
  },
  {
    "caption": "(F) Representative immunofluorescence images showing Ki67/Pcad expression (upper) and Cd34/Ki67 expression (lower) in Sirt7fl/fl and Sirt7f/f;K15-Cre HFs on P56, P74 and P85. The white dashed line indicates bulge of hair follicle.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Sirt7: 209011"
  },
  {
    "caption": "(A) Representative colonies formed by Sirt7+/+, Sirt7-/- and Sirt7-TG bulge SCs that were purified from telogen-phase HFs and allowed to grow for 2 weeks. (B-C) Quantifications of colony number and size in (A); n = 3 mice per genotype. ",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "Immunoblot analysis of the indicated proteins in HFSC colonies from Sirt7+/+, Sirt7-/- and Sirt7-TG mice (D)",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "proteins in HFSC colonies from Sirt7+/+, Sirt7-/- and Sirt7-TG mice Nfatc1 protein levels were quantified using Image J Plus 6.0 (E, n = 3 mice for each group).",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(F) Immunoblot analysis of the NFATc1 expression level in human keratinocyte HaCaT cells treated with SIRT7 siRNAs.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "(G) Immunoblot analysis of the NFATc1 expression in the presence of ectopic SIRT7 expression in HaCaT cells.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "(H) NFATc1 luciferase activity was monitored in HEK293T cells after the indicated treatments (n=3). The relative luciferase activity was determined by dual luciferase reporter assay.",
    "ncbi_link": "NFATc1: 4772"
  },
  {
    "caption": "(I-J) IHC analyses of Nfatc1 expression in hair follicles of Sirt7f/f, Sirt7f/f ;K15-Cre and Sirt7-TG mice at the indicted time points. The black dashed line indicates the bulge (Bu) of hair follicle.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Sirt7: 209011"
  },
  {
    "caption": "(K-L) qPCR analysis of Nfatc1-targeted genes in HFSCs colonies cultured from Sirt7+/+, Sirt7-/-and Sirt7-TG mice, n=3 for each genotypes.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(A) Representative immunoblots showing NFATc1 degradation in HEK293T cells stably overexpressing NFATc1 in the presence of cycloheximide (CHX), with or without SIRT7 overexpression. (B) Quantification of NFATc1 levels in (A) from 3 independent experiments. ",
    "ncbi_link": "NFATc1: 4772
SIRT7: 51547"
  },
  {
    "caption": "(C) Immunoblots of Nfatc1 protein levels in Sirt7+/+ and Sirt7-/- keratinocytes. (D) Quantification of Nfatc1 levels in (C) from 3 independent experiments. ",
    "ncbi_link": "Sirt7: 51547"
  },
  {
    "caption": "(E-F) Immunoblots (E) and related quantitative data (F, n=3) showing NFATc1 protein levels in HEK293T cells overexpressing wildtype HA-SIRT7 or a SIRT7 enzyme-dead mutant (H187Y).",
    "ncbi_link": "HA: 
SIRT7: 51547"
  },
  {
    "caption": "(G-H) Immunoblots (G) and quantitative data (H, n=3) showing NFATc1 levels in HEK293T cells transfected with NFATc1-CA, with or without ectopic SIRT7, treated with MG132.",
    "ncbi_link": "NFATc1: 4772
SIRT7: 51547"
  },
  {
    "caption": "Immunoblots showing the interaction (by co-immunoprecipitation) between ectopic NFATc1/PA28γ in HEK293T cells (K) (L) after manipulating SIRT7 levels.",
    "ncbi_link": "NFATc1: 4772
PA28γ: 10197
SIRT7: 51547"
  },
  {
    "caption": "Immunoblots showing the interaction (by co-immunoprecipitation) between endogenous NFATc1/PA28γ in HaCaT cells (L) after manipulating SIRT7 levels.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "(M-N) Immunoblot (M) and quantitative data (N, n=3) analysis of NFATc1 levels upon overexpression of HA-SIRT7 with or without PA28γ oligo siRNAs treatment.",
    "ncbi_link": "HA: 
PA28γ: 10197
SIRT7: 51547"
  },
  {
    "caption": "(O) Co-immunoprecipitation between NFATc1 and PA28γ in HEK293T cells cotransfected with WT HA-SIRT7 or an enzyme-dead mutant (H187Y).",
    "ncbi_link": "HA: 
SIRT7: 51547"
  },
  {
    "caption": "(A) IHC staining of Nfatc1 expression in HFs on P84 in Sirt7+/+ and Sirt7-/- mice with or without Cyclosporin A (CsA) treatment. The black dashed line indicates bulge (Bu) of hair follicle. (B) Quantitative analysis of Nfatc1 levels in (A, n=10 hair follicles) using ImageJ plus 6.0. ",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(C) Immunofluorescent staining of Ki67 and Pcad at P84 in Sirt7+/+ and Sirt7-/- HFs with or without CsA treatment.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(E) Images were captured of the hair coats of Sirt7+/+ and Sirt7-/- mice at 15 months. The yellow dashed lines indicate hair thinning or hair loss.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(F) Immunofluorescence and IHC staining of Nfatc1 and Sirt7 in HFs of 15-month-old Sirt7+/+ and Sirt7-/- mice. The white/black dashed line indicates bulge (Bu) of hair follicle.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(H) Images captured of the skin in the plucked regions (blue dotted lines) of WT (3 months), aged WT (20 months) and aged Sirt7-TG mice (20 months), 14 days after depilation. Pigmentation of the skin indicates hair regrowth. n = 3 mice per genotype.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(I) Hair re-growth scores were analyzed for young WT, old WT and old Sirt7-TG mice in (H), n=3 mice for each group.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(J) The hair coat recovery score (described in methods) after the back hair of old WT and old Sirt7-TG mice was shaved. n = 3 mice per genotype.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "(K) Images captured of the hair coats of WT and Sirt7-TG mice at 28 months-of-age. The yellow dashed lines indicate the hair thinning or hair loss regions.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "C. qPCR analysis of SATB2 mRNA expression in GSCs and matched non-stem tumor cells (NSTCs) (n=5).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "F. qPCR analysis of SATB2 mRNA expression in GSCs and neural progenitor cells (NPCs) (n=3).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "A. Immunoblot analysis of SATB2 expression in GSCs transduced with lentiviral-mediated non-targeting shRNA (shNT) or SATB2 shRNA (shSATB2).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "B. Cell viability of GSCs transduced with shNT or shSATB2 (n=5).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "C. EdU incorporation assay of GSCs transduced with shNT or shSATB2. Scale bar: 50 μm. D. Quantification of (C) showing the percentage of EdU+ cells (n=5). ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "E. Tumorsphere images of GSCs transduced with shNTor shSATB2. Scale bar: 100 μm. Quantification of the diameter of tumorspheres formed by GSCs expressing shNT or shSATB2 (F: n=9; G: n=5).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "G. Quantification of the number of tumorspheres formed by GSCs expressing shNT or shSATB2 (F: n=9; G: n=5).",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "H. In vitro limiting dilution analysis of the tumorsphere formations of GSCs expressing shNT or shSATB2. Silencing SATB2 attenuated the self-renewal capacity of GSCs.",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " A. Bioluminescent images of the GBM xenografts derived from the luciferase-labeled T3359 GSCs expressing NT or SATB2 shRNA. Representative images on day 21 posttransplantation are shown (n=5 mice per group). Silencing SATB2 significantly delayed GBM growth . B. Quantification of the bioluminescence of xenografts derived from the luciferase-labeled T3359 GSCs expressing shNT or shSATB2 on day 21 posttransplantation (n=5 mice per group).",
    "ncbi_link": "luciferase: 
SATB2: 23314"
  },
  {
    "caption": " C. Kaplan-Meier survival curves of mice intracranially implanted with T3359 GSCs expressing shNT or shSATB2 (shNT: n=7 mice; shSATB2-1 or shSATB2-2: n=5 mice). Median survival: shNT, 28 days; shSATB2-1, 48 days; shSATB2-2, 45 Days. Animals bearing GSC-derived xenografts expressing SATB2 shRNA survived longer than the control animals. ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " D. Immunofluorescence of SATB2 (Green) in xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=5 tumors per group). Scale bar: 40 μm. E. Quantification of SATB2 intensity in xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=5 tumors per group). ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " F. Immunofluorescence of Ki67 (Green) in tumor xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=5 tumors per group). Scale bar: 40 μm. G. Quantification of Ki67 positive cells in xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=5 tumors per group). ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " H. Immunofluorescence of SOX2 (Red) in xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=4 tumors per group). Scale bar: 40 μm. I. Quantification of SOX2 positive cells in xenografts derived from T3359 GSCs expressing shNT or shSATB2 (n=4 tumors per group). ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " A. Heatmap analysis of differentially expressed genes between SATB2 silencing H2S GSCs (shSATB2) and control H2S GSCs (shNT). Differentially expressed genes had a 1.8-fold or greater expression difference. Among differentially expressed genes, 160 are upregulated and 185 are downregulated. ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "C. qPCR analysis of FOXM1 and SATB2 mRNA expression in GSCs transduced with shNT or shSATB2 (n=3).",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": "D. Immunoblot analysis of FOXM1 and SATB2 expression in GSCs transduced with shNT or shSATB2.",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": "E. Immunoblot analysis of FOXM1 and SATB2 expression in tumor xenografts-derived from T3359 GSCs expressing shNT or shSATB2.",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " F. Heatmap analysis of FOXM1 downstream targets between SATB2 silencing H2S GSCs (shSATB2) and control H2S GSCs (shNT) from microarray analysis. Differentially expressed genes had a 1.5-fold or greater expression difference. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " G. qPCR analysis of FOXM1 downstream targets in H2S GSCs transduced with shNT or shSATB2 (n=3). ",
    "ncbi_link": "SATB2: 23314"
  },
  {
    "caption": " A. Immunoblot analysis of FOXM1 and SATB2 expression in T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " B. Cell viability assay of T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (n=5). Ectopic expression of FOXM1 restored the cell proliferation impaired by SATB2 silencing. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " C. Tumorsphere number of T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (n=5). Ectopic expression of FOXM1 restored the tumorsphere formation of GSCs impaired by SATB2 silencing. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " In vivo bioluminescent images of the tumor xenografts derived from luciferase-labeled T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=5 mice; shNT+FOXM1: n=4 mice; shSATB2: n=5 mice; shSATB2+ FOXM1: n=5 mice). Representative images on day 21 posttransplantation are shown. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly restored GBM tumor growth. ",
    "ncbi_link": "luciferase: 
FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " E. In vivo bioluminescent images or quantification of the tumor xenografts derived from luciferase-labeled T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=5 mice; shNT+FOXM1: n=4 mice; shSATB2: n=5 mice; shSATB2+ FOXM1: n=5 mice). Representative images on day 21 posttransplantation are shown. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly restored GBM tumor growth. ",
    "ncbi_link": "luciferase: 
FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " F. Kaplan-Meier survival curves of mice intracranially implanted with T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=8 mice; shNT+FOXM1: n=7 mice; shSATB2: n=6 mice; shSATB2+ FOXM1: n=8 mice). Median survival: shNT, 30 days; shNT+FOXM1, 28 days; shSATB2, 50.5 Days; shSATB2+FOXM1, 34 days. Ectopic expression of FOXM1 in GSCs expressing shSATB2 markedly attenuated the increased survival of mice bearing the GSC-derived GBMs. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " G. Immunofluorescence of Ki67 (Green) in xenografts derived from T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=6 tumors; shNT+FOXM1: n=5 tumors; shSATB2: n=6 tumors; shSATB2+ FOXM1: n=6 tumors). Scale bar: 40 μm. H. Quantification of Ki67 positive cells in xenografts derived from T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=6 tumors; shNT+FOXM1: n=5 tumors; shSATB2: n=6 tumors; shSATB2+ FOXM1: n=6 tumors). ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " I. Immunofluorescence of SOX2 (Red) in xenografts derived from T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=6 tumors; shNT+FOXM1: n=5 tumors; shSATB2: n=6 tumors; shSATB2+ FOXM1: n=6 tumors). Scale bar: 40 μm. J. Quantification of SOX2 positive cells in xenografts derived from T3359 GSCs transduced with FOXM1 or vector control in combination with shNT or shSATB2 (shNT: n=6 tumors; shNT+FOXM1: n=5 tumors; shSATB2: n=6 tumors; shSATB2+ FOXM1: n=6 tumors). ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " B. ChIP assays with the SATB2 antibody or IgG using GSCs, NSTCs and NPCs. PCR primers amplified a fragment flanking the MAR of FOXM1 gene locus. Note that abundant SATB2 binds to the MAR of FOXM1 gene locus in GSCs. ",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": " C. qPCR analysis of ChIP assays with the SATB2 antibody or IgG using GSCs transduced with shNT or shSATB2 (n=3). PCR primers amplified a fragment flanking the MAR of FOXM1 gene locus. Silencing SATB2 decreased its binding amount to the MAR of FOXM1 gene locus. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " E. qPCR analysis of ChIP assays with the CBP antibody or IgG using GSCs transduced with shNT or shSATB2 (n=3). PCR primers amplified a fragment flanking the MAR of FOXM1 gene locus. Silencing SATB2 reduced the binding of CBP to the MAR of FOXM1 gene locus. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " F. qPCR analysis of ChIP assays with the indicated antibody (AcH3K18, AcH3K27, AcH4) using T3359 GSCs transduced with shNT or shSATB2 (n=3). PCR primers amplified a fragment flanking the MAR of FOXM1 gene locus. Silencing SATB2 reduced acetylation of H3K18, H3K27 and H4 levels on the MAR of FOXM1 locus. ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " G. qPCR analysis of FOXM1 mRNA expression in T3359 GSCs transduced with shSATB2 or shCBP or both (n=3). ",
    "ncbi_link": "CBP: 1387
FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": " H. Immunoblot analysis of FOXM1 expression in T3359 GSCs transduced with shSATB2 or shCBP or both. ",
    "ncbi_link": "CBP: 1387
SATB2: 23314"
  },
  {
    "caption": " C. qPCR analysis of SATB2, FOXM1 and FOXM1 downstream targets in T3359 GSCs treated with indicated doses of C646 or the vehicle control for 24 hours (n=3). ",
    "ncbi_link": "FOXM1: 2305
SATB2: 23314"
  },
  {
    "caption": "E. Bioluminescent imaging of tumor growth in mice bearing xenografts derived from the luciferase-labeled T3359 GSCs treated with C646 or the vehicle control at indicated days after GSC transplantation (n=5 mice per group). F. Quantification of tumor growth from (E) (n=5 mice per group).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "Co-IP from 293T cells 48 h after transfection. RhoJ-PlexinD1 binding was disrupted by deleting the RBD or ECD of PlexinD1 and by 30-min stimulation with Sema3E. Arrows indicate PD1 Full (upper, 250 kDa) and PD1△RBD (lower, 1.7 kDa smaller than PD1 Full).",
    "ncbi_link": "PlexinD1: 67784"
  },
  {
    "caption": "Immunoblots in siRNA-transfected HUVECs. Note the early and transient activation of PLCγ, Erk1/2, and Akt, but not p38 MAPK, in RhoJ-knockdown ECs.",
    "ncbi_link": "RhoJ: 57381"
  },
  {
    "caption": "Quantification of the kinetics of EC migration. Values of forward and reverse migration for RhojWT/WT are normalized to 1. n = 33 vessel branches per group.",
    "ncbi_link": "Rhoj: 80837"
  },
  {
    "caption": "Quantification of vessel elongation (left graph). n = 33 vessel branches per group. Scatter plot shows relationship between "vessel elongation" and "reverse migration" in RhojGFP/GFP aortic rings as evaluated by a Pearson correlation coefficient.",
    "ncbi_link": "Rhoj: 80837"
  },
  {
    "caption": "Labeling for YFP/GFP (green), CD31 (red), and ETS transcription factor ERG (blue) in retinal vascular fronts of P5 CAG-MerCreMer:R26R-EYFPflox/WT and CAG-MerCreMer:Rhojfloxflox mice after intraperitoneal (i.p.) injections of 10 µg of 4-hydroxytamoxifen (4OHT) at P1. Scale bar, 50 µm.   Relative contribution of YFP/GFP-positive ECs to the tip positions. n = 16 per group. Values for CAG-MerCreMer:R26R-EYPflox/WT are normalized to 1.   ",
    "ncbi_link": "ETS: 
Rhoj: 80837"
  },
  {
    "caption": "Labeling for GFP (green) and CD31 (red) in retina of P4 RhojGFP/GFP mouse. Scale bar, 200 µm (left); 20 µm (right).",
    "ncbi_link": "Rhoj: 80837"
  },
  {
    "caption": "Labeling for EdU (green), ERG (red), and CD31 (gray) in retinas of P4 RhojWT/WT and RhojGFP/GFP mice 2 h after i.p. EdU injections. Scale bar, 20 µm. The graph shows EC proliferation index in retinal capillaries behind the angiogenic fronts. n = 12 per group.",
    "ncbi_link": "GFP: 
Rhoj: 80837"
  },
  {
    "caption": "Labeling for CD31 in retinas of P4 and P7 RhojWT/WT and RhojGFP/GFP mice. Scale bars, 500 µm.",
    "ncbi_link": "GFP: 
Rhoj: 80837"
  },
  {
    "caption": "Morphometric analyses of retinal vessels in RhojWT/WT (P4, n = 18; P7, n = 8) and RhojGFP/GFP (P4, n = 16; P7, n = 11) mice.",
    "ncbi_link": "GFP: 
Rhoj: 80837"
  },
  {
    "caption": "Labeling for CD31 in retinas of P4 Rhojflox/flox and Pdgfb-iCreERT2:Rhojflox/flox (RhojiΔEC) mice after single i.p. injection of 100 µg of 4OHT at P1. Scale bar, 500 µm.",
    "ncbi_link": "iCreERT2: 
Pdgfb: 18591
Rhoj: 80837"
  },
  {
    "caption": "Morphometric analyses of retinal vessels in P4 Rhojflox/flox (n = 7) and Rhoji∆EC (n = 6) mice.",
    "ncbi_link": "Rhoj: 80837"
  },
  {
    "caption": "Labeling for GFP (green) and CD31 (red) in retina of P18 OIR-RhojGFP/WT mouse. Scale bar, 200 µ",
    "ncbi_link": "GFP: 
Rhoj: 80837"
  },
  {
    "caption": "Labeling for CD31 in retinas of P18 OIR-Rhojflox/flox and OIR-Rhoji∆EC mice after daily i.p. injection of 200 µg of 4OHT from P12. Scale bar, 500 µm. Quantification of areas of neovascular tufts in P18 OIR-Rhojflox/flox and OIR-Rhoji∆EC mice. n = 6 per group.",
    "ncbi_link": "Rhoj: 80837"
  },
  {
    "caption": "(B-C) HEK293 cells were transfected with empty vector or plasmids encoding HA tagged KDF1 and/or GST-tagged IKKα. Immunoprecipitation (α-HA or α-GST) was carried out to determine their interaction. Immunoprecipitates (IP) and whole cell lysate (WCL) were immunoblotted (IB) with different antibodies as indicated.",
    "ncbi_link": "GST: 
HA: 
IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(E) HEK293 cells were transfected to co-express HA-tagged KDF1 with GST-tagged IKKα or its kinase dead (KD) mutant. IP and WCL were blotted with different antibodies as indicated.",
    "ncbi_link": "GST: 
HA: 
IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(F) HEK293 cells were transfected to co-express HA-tagged KDF1 with GST-tagged IKKα or its different truncation mutants (EV Fig. 1B). IP and WCL were blotted with different antibodies as indicated. Arrow denotes antibody heavy chain.",
    "ncbi_link": "GST: 
HA: 
IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(G) HEK293 cells were transfected to co-express GST-tagged IKKα with HA-tagged KDF1 or its different truncation mutants (EV Fig. 1C). IP and WCL were blotted with different antibodies as indicated.",
    "ncbi_link": "GST: 
HA: 
IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(A) H/E staining of E18.5 skin sections from WT, IKKα KO, and KDF1 KO mice. Dotted lines denote dermal-epidermal boundaries. Epi: epidermis, Der: dermis. Scale bar=50 μm. (B) E18.5 skin sections from WT, IKKα KO, and KDF1 KO mice were immunostained with different antibodies as indicated (Krt14: Keratin 14, Krt10: Keratin 10, Lor: Loricrin, β4: β4-integrin, CD104). Dotted lines denote dermal-epidermal boundaries. Epi: epidermis, Der: dermis. Scale bar=100 μm. ",
    "ncbi_link": "IKKα: 12675
KDF1: 69073"
  },
  {
    "caption": "A) Immunoblots of WCL from IKKα KO cells with rescued expression of HA-tagged IKKα or its mutant using different antibodies as indicated.",
    "ncbi_link": "HA: 
IKKα: 12675"
  },
  {
    "caption": "B) Immunoblots of WCL from KDF1 KO cells with rescued expression of KDF1 or its mutant using different antibodies as indicated. Expression f exogenous KDF1 was induced by doxycycline (DOX) at different concentration.",
    "ncbi_link": "KDF1: 69073"
  },
  {
    "caption": "E) Sections of regenerated skin developed from engrafted IKKα KO, KDF1 KO, and their rescued cells were immunostained with different antibodies as indicated. Dotted lines denote dermal-epidermal boundaries. Epi: epidermis, Der: dermis. Scale bar=50 μm.",
    "ncbi_link": "IKKα: 12675
KDF1: 69073"
  },
  {
    "caption": "(A) WCL from WT and KDF1 KO cells before and after calcium shift were immunoblotted with different antibodies as indicated. Lo: low calcium; Hi: high calcium.",
    "ncbi_link": "KDF1: 69073"
  },
  {
    "caption": "(B-C) WT and KDF1 KO keratinocyte were treated with 20nM cycloheximide (CHX). WCL was collected at 0, 30, 60, 90, 120 min post CHX treatment and subjected to immunoblotting with IKKα antibody (B). Band intensity is determined by densitometry and the amount of IKKα is calculated and quantified (C). Statistical analysis is conducted using 2-way ANOVA. N=3 (biological replicates). *, p<0.05. Error bar represents S.D. (standard deviation).",
    "ncbi_link": "KDF1: 69073"
  },
  {
    "caption": "(D-E) WT and KDF1 KO keratinocyte (right panels) or cells transfected with plasmid encoding exogenous IKKα (left panels) were treated with MG132 at 10µM for 6 hours, then were subjected to immunoprecipitation using anti-ubiquitin (Ub) antibody. IP and WCL were analyzed by immunoblots with α-IKKα antibody (D). Overall intensity of all ubiquitinated IKKα bands was determined by densitometry. Ratio of ubiquitinated IKKα was quantified and presented as bar graphs (E). Statistical analysis is conducted using unpaired Student's t-test. Error bar represents S.D. (standard deviation). N=3 (biological replicates). *, p<0.05. Kd: kilodalton for molecular weight markers.",
    "ncbi_link": "IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(F) IKKα protein level in KDF1 KO keratinocyte expressing WT KDF1 or KDF1 mutant, under both low and high calcium conditions, was examined and quantified by western blotting",
    "ncbi_link": "KDF1: 69073"
  },
  {
    "caption": "(G) PiggyBac transposon was used to ectopically express HA-tagged IKKα in KDF1 deficient cells. WCL were collected and analyzed by immunoblots with different antibodies as indicated.",
    "ncbi_link": "HA: 
IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "(H) Overexpression of IKKα in KDF1 KO keratinocyte can restore normal skin stratification. Skin sections from grafted tissue were immunostained with different antibodies as indicated. Dotted lines denote dermal-epidermal boundaries. Epi: epidermis, Der: dermis. Scale bars = 50 µm.",
    "ncbi_link": "IKKα: 1147
KDF1: 69073"
  },
  {
    "caption": "A) HEK293 cells were transfected to co-express KDF1 with USP7. IP and WCL were blotted with different antibodies as indicated.",
    "ncbi_link": "KDF1: 69073
USP7: 252870"
  },
  {
    "caption": "C) WCL from WT and USP7 CRISPR KO cells were subjected to immunoblotting with different antibodies as indicated.",
    "ncbi_link": "CRISPR: 
USP7: 252870"
  },
  {
    "caption": "D) IKKα protein level in WT and USP7 KO keratinocyte were examined by immunoblotting before and after calcium shift.",
    "ncbi_link": "USP7: 252870"
  },
  {
    "caption": "E) WT and USP7 KO keratinocyte were treated with MG132 at 10μM for 6 hours, then subjected to immunoprecipitation using anti-ubiquitin antibody. Precipitated product was analyzed by immunoblotting with IKKα antibody. Band intensity was determined by densitometry and shown as bar graphs. Statistical analysis is conducted using unpaired Student's t-test. Error bar represents S.D. (standard deviation). N=3 (biological replicates). **, p<0.01. Kd: kilodalton for molecular weight markers.",
    "ncbi_link": "USP7: 252870"
  },
  {
    "caption": "F-G) Immunoblot of Krt10 and Loricrin (Lor) with WT and USP7 KO cells before and after calcium shift (F). Star denotes an unspecific band in α-Loricrin blots. Band intensity was determined by densitometry and shown as bar graphs",
    "ncbi_link": "USP7: 252870"
  },
  {
    "caption": "H) Sections of engrafted skin developed from USP7 KO or control WT cells were immunostained with different antibodies as indicated. Dotted lines denote dermal-epidermal boundaries. Epi: epidermis, Der: dermis. Scale bar=100μm.",
    "ncbi_link": "USP7: 252870"
  },
  {
    "caption": "(A) Clone P15 induces HA-LC3 lipidation. 293T cells were transfected with P15 plus plasmids expressing HA-LC3A and/or the apoptotic inhibitor p35 (as shown), and lysed for western blotting against the indicated molecules (anti‐HA for HA-LC3A). The figure shows that expression of P15 induces HA-LC3A conversion to a lower molecular weight form indicative of protein lipidation. This activity remains unchanged by p35.",
    "ncbi_link": "P15: 
LC3A: 84557"
  },
  {
    "caption": "(B) P15 induces GFP-LC3 translocation to a vesiculated pattern. 293T cells were transfected with the indicated plasmids mixed with vectors expressing GFP-LC3A and p35. The known autophagic inducer bNIP3L constituted a positive control. Representative confocal microscopy pictures are shown.",
    "ncbi_link": "P15: 
bNIP3L: 665
LC3A: 84557"
  },
  {
    "caption": "(C) TMEM59 induces HA-LC3 lipidation in different cell lines lacking the SV40 large T−antigen plasmid amplification system. Cells were transfected with the shown plasmids, vectors expressing HA-LC3A (left) or HA-LC3B (right) and GST (as transfection control), and lysed for western blotting against the indicated molecules.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
large T−antigen: 1489531
TMEM59: 9528"
  },
  {
    "caption": "(D) TMEM59 induces GFP-LC3 activation. 293 cells were transfected with the indicated plasmids and GFP-LC3A (top) or GFP-LC3B (bottom). Representative confocal microscopy pictures are shown.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(A) TMEM59 ID is required for HA-LC3 lipidation. 293 cells were transfected with full‐length TMEM59 (FL) or a deleted version lacking the ID (ΔID, Δ263-323), HA-LC3A (left) or HA-LC3B (right) and GST. Cells were lysed for western blotting against the shown molecules.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(B) The ID is necessary for GFP-LC3 activation. 293 cells were transfected with the indicated TMEM59 constructs and GFP-LC3A or GFP-LC3B (as indicated). Representative confocal pictures are shown.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(D) TMEM59 ID (amino acids 263-323) suffices for HA-LC3A lipidation. 293 cells were transfected with the indicated CD16:7 chimera (Control: empty chimera) and vectors encoding HA-LC3A and GST, subjected to aggregation with the shown amounts of anti‐CD16 antibody and lysed for western blotting. The right panel shows control WBs demonstrating equal loading (ACTIN), transfection (GST) and chimera expression (CD16) in unaggregated samples, as all experimental points per chimera derive from a single transfection.",
    "ncbi_link": "CD16: 2215///2214
TMEM59: 9528"
  },
  {
    "caption": "(E) Comparable surface levels of CD16:7 constructs. Transfected 293 cells were processed for anti‐CD16 flow cytometry. The graph displays percentages of positive cells (left axis) and means of fluorescence of positive cells (MF, right axis) obtained from triplicates. Data are expressed as means ±s.d. of the triplicates.",
    "ncbi_link": "CD16: 2215///2214"
  },
  {
    "caption": "(G) The ID suffices for GFP-LC3 activation. 293 cells were transfected with the indicated chimeras and GFP-LC3A or GFP-LC3B, aggregated and mounted. Representative confocal microscopy pictures are shown. Activated GFP-LC3 appears as a collapsed mass of indiscernible vacuoles.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631"
  },
  {
    "caption": "(A, B) Ability of serial C‐terminal deletions of TMEM59 to activate LC3. 293 cells were transfected with the indicated TMEM59 C‐terminal deletions, HA-LC3A (A) or HA-LC3B (B) and GST, and lysed for western blotting against the indicated molecules.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(C) Amino acids 263-281 retain the full potential of TMEM59 ID to promote HA-LC3 conversion. 293 cells were transfected with the shown CD16:7 chimeras, HA-LC3A or HA-LC3B (as indicated) and GST, and subjected to anti‐CD16 aggregation before lysing them for western blotting. The lower panels show control WBs (unaggregated samples).",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "D Amino acids 263-281 suffice for GFP-LC3 activation and retain the full potential of TMEM59 ID to promote GFP-LC3 activation. 293 cells were transfected with the indicated CD16:7 chimeras and GFP-LC3A or GFP-LC3B (as indicated), and subjected to anti‐CD16 aggregation before fixing them for microscopy. The graph shows percentages of transfected cells exhibiting redistributed GFP-LC3. Quantification and data expression were done as in Figure 2H.",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(E) Amino acids 282-323 of TMEM59 lack LC3 activation potential. 293 cells were transfected with the shown chimeras, HA-LC3A or HA-LC3B and GST, and processed for western blotting against the indicated molecules. Control WBs of unaggregated samples are shown in the lower panels.",
    "ncbi_link": "LC3A: 84557
LC3B: 81631
TMEM59: 9528"
  },
  {
    "caption": "(F) Surface expression levels of CD16:7 chimeras. Procedures and data expression were as in Figure 2E. The figure shows that the functional differences observed between CD16:7 chimeras (C-E) are not caused by differential surface expression.",
    "ncbi_link": "CD16: 2215///2214"
  },
  {
    "caption": "(A) Endocytic vesicles containing aggregated CD16:7-263-281 become labelled with GFP-LC3. JAR cells were transfected with vectors expressing the indicated CD16:7 chimeras and GFP-LC3A, and subjected to anti‐CD16 aggregation for 8 h before staining for the endocytosed chimera (red). Representative confocal pictures are shown. The inset highlights a vesicle where the peripheral GFP-LC3 staining is particularly distinguishable. The right panel displays control WBs showing that chimera aggregation for 8 h activates HA-LC3A conversion in JAR cells.",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557"
  },
  {
    "caption": "(C) Immunoelectron microscopy assay showing that endocytosed CD16:7-263-281 localizes to LC3−labelled, single−membrane vesicles. JAR cells were transfected with the CD16:7-263-281 chimera and a construct expressing human IgG1 fused to LC3A. Cells were subjected to anti−CD16 aggregation for 8 h and processed for immunoelectron microscopy. Thick gold signal (18 nm): aggregated, endocytosed chimera; thin gold signal (12 nm): IgG1-LC3. Arrows indicate single membrane (black) or IgG1-LC3A (white). Scale bar: 400 nm.",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557"
  },
  {
    "caption": "(D) Lysosomal inhibition increases HA-LC3II levels promoted by CD16:7-263-281. 293 cells were transfected with the indicated chimera and HA-LC3A, and subjected to anti−CD16 aggregation in the absence or presence of bafilomycin (200 nM, added 4 h post aggregation) before lysing them for western blotting against the indicated molecules.",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557"
  },
  {
    "caption": "(E) Aggregation of CD16:7-263-281 promotes its own degradation. 293 cells were transfected with the indicated constructs, aggregated and lysed for western blotting. Shown are overexposed anti‐CD16 WBs.",
    "ncbi_link": "CD16: 2215///2214"
  },
  {
    "caption": "(F) Degradation of CD16:7-263-281 is inhibited by ATG5 depletion. 293 cells were transfected with the indicated siRNAs and subsequently with the shown CD16:7 constructs, aggregated and lysed for anti‐CD16 western blotting (left panel). The right panel displays control WBs showing ATG5 depletion.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "ATG5: 9474
CD16: 2215///2214"
  },
  {
    "caption": "(A) Identification of critical amino acids for HA-LC3 conversion. 293 cells were transfected with the indicated CD16:7-263-281 mutants and HA-LC3A, subjected to anti‐CD16 aggregation and lysed for western blotting against the indicated molecules. Asterisks mark mutations with reduced activity. Shown is one representative experiment of six repetitions.",
    "ncbi_link": "CD16: 2215///2214
LC3A: 84557"
  },
  {
    "caption": "(D) Simultaneous mutation of the four essential amino acids to alanine blocks HA-LC3 conversion induced by CD16:7-263-281. 293 cells were transfected with the indicated chimeras (4M, quadruple mutant) and HA-LC3A, aggregated and lysed for western blotting.",
    "ncbi_link": "CD16: 2215///2214
LC3: 440738///81631///84557"
  },
  {
    "caption": "(E) Simultaneous mutation of the four essential amino acids blocks GFP-LC3 activation and colocalization with the endocytosed chimera. JAR cells were transfected with the indicated CD16:7-263-281 constructs and GFP-LC3A, aggregated and stained for the endocytosed chimera (red). Representative confocal microscopy images are shown.",
    "ncbi_link": "CD16: 2215///2214
LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) Apposition events between GFP-ATG16L1 and endocytosed CD16:7-263-281. JAR cells were transfected with CD16:7-263-281 and GFP-ATG16L1 or GFP-BECLIN (as indicated), aggregated for 4 h and stained for the endocytosed chimera (red). Representative confocal microscopy pictures are shown. Two different examples are provided for GFP-ATG16L1.",
    "ncbi_link": "ATG16L1: 55054
CD16: 2215///2214"
  },
  {
    "caption": "(B-D) 293T cells were transfected with the indicated constructs, lysed and subjected to GST immunoprecipitation using agarose beads coupled to glutathione (IP, immunoprecipitation; TL, total lysate). Shown are WBs against the indicated molecules. (B) AU-ATG16L1 co‐precipitates with wild‐type (WT) TMEM59-GST but not with a mutated version where the four essential amino acids were mutated to alanine (TMEM59-4M-GST). (C) Full‐length TMEM59 and TMEM59-Δ282 co‐precipitate with GST-ATG16L1, whereas the respective 4M versions do not. (D) AU-ATG16L1 co‐precipitates with a fusion protein between GST and the minimal active peptide of TMEM59 (GST-263-281), but not with a 4M version (GST-263-281-4M) or a GST fusion protein with the inactive portion of TMEM59-ID (GST-282-323).",
    "ncbi_link": "ATG16L1: 55054
TMEM59: 9528"
  },
  {
    "caption": "(E) HA-ATG16L1 expressed in bacteria co−precipitates with a GST-263-281 recombinant protein purified from bacterial cultures, but not with a 4M version of the same construct or GST-282-323. The indicated GST partners were expressed in bacteria and purified using agarose beads coupled to glutathione. The loaded beads were then used for HA-ATG16L1 pull−down from crude bacterial lysates. Shown are WBs against the indicated molecules (PD, pull−down). A Coomasie staining of a protein gel with the purified GST fusion proteins is shown. The right panel compares the amount of HA-ATG16L1 pulled down by GST-263-281 with the signal provided by direct anti−HA immunoprecipitation. This result shows that about 20-25% of the available HA-ATG16L1 protein is precipitated by GST-263-281. Asterisks indicate irrelevant bands in B and D.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(A-F) 293T cells were transfected with the indicated constructs, lysed and subjected to GST immunoprecipitation with agarose beads coupled to glutathione. Shown are WBs against the indicated molecules. (A) A deleted version of ATG16L1 lacking the WD domain (HA-ATG16L1-ΔWD) does not co‐precipitate with TMEM59-GST. (B) TMEM59 does not co‐precipitate with ATG16L1-ΔWD fused to GST. (C) The WD domain of ATG16L1 (HA-ATG16L1-WD) suffices to co‐precipitate with TMEM59-GST. (D) TMEM59 co‐precipitates with ATG16L1-WD fused to GST. (E) HA-ATG16L1-WD does not bind a 4M version of TMEM59-GST. (F) TMEM59-4M does not co‐precipitate with the ATG16L1-WD fused to GST.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "ATG16L1: 55054
TMEM59: 9528"
  },
  {
    "caption": "(C, D, E, G, H) 293T cells were transfected with the indicated constructs, lysed and subjected to GST immunoprecipitation with agarose beads coupled to glutathione. Shown are WBs against the indicated molecules. (C) The N‐terminal CARD of NOD2 (NOD2-CARD1-HA), but not the CARD of NOD1 (NOD1-CARD-HA), co‐precipitates with GST-ATG16L1. (D) The ID of TLR2 (HA-TLR2-ID) co‐precipitates with GST-ATG16L1. (E) Mutated versions (MUT) of NOD2-CARD1-HA and HA-TLR2-ID (as shown) do not co‐precipitate with GST-ATG16L1. (F) Amino‐acid sequences of T3JAM and DEDD2 including the motif. Residues identified by the Prosite algorithm are highlighted. (G) Wild‐type (WT) versions of HA-T3JAM and HA-DEDD2 (as indicated) co‐precipitate with GST-ATG16L1. (H) Mutated versions (MUT) of HA-T3JAM and HA-DEDD2 do not co‐precipitate with GST-ATG16L1. Asterisks indicate irrelevant bands in C, D and G.Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "ATG16L1: 55054
DEDD2: 162989
NOD1: 10392
NOD2: 64127
TLR2: 7097
T3JAM: 80342"
  },
  {
    "caption": "(A) Depletion of TMEM59 inhibits LC3II generation by SA at early infection times. HeLa cells were transfected with the indicated siRNAs and, 48 h later, infected with the bacteria (SA) for the shown times before lysing them for western blotting against the indicated molecules. The right panel shows successful TMEM59 depletion (rabbit anti‐TMEM59 immunoprecipitation plus chicken anti‐TMEM59 WB).",
    "ncbi_link": "TMEM59: 9528"
  },
  {
    "caption": "(A) The right panel shows successful TMEM59 depletion (rabbit anti‐TMEM59immunoprecipitation plus chicken anti‐TMEM59WB).",
    "ncbi_link": "TMEM59: 9528"
  },
  {
    "caption": "(E) Depletion of TMEM59 reduces recovery of SA from infected cells. HeLa cells were transfected with the indicated siRNAs, infected with SA 96 h later (5 h, moi=0.1) and lysed for CFU evaluation. The experiment was carried out three independent times. The graph displays average CFU counts obtained for the 10−1 dilution of the relevant extracts, ±s.d. of the three data sets. Asterisks indicate significant differences (P<0.01, paired Student's t‐test).",
    "ncbi_link": "TMEM59: 9528"
  },
  {
    "caption": "(E) Depletion of TMEM59 reduces recovery of SA from infected cells. HeLa cells were transfected with the indicated siRNAs, infected with SA 96 h later (5 h, moi=0.1) and lysed for CFU evaluation. The experiment was carried out three independent times. The right panel shows successful TMEM59 depletion (anti‐TMEM59 immunoprecipitation plus anti‐TMEM59 WB).Source data for this figure is available on the online supplementary information page.",
    "ncbi_link": "TMEM59: 9528"
  },
  {
    "caption": "A Double-plotted representative actograms of the indicated genotypes. Flies are monitored in LD for 4 days and then DD for 7 days. Dicer2 (dcr2) is co-expressed to enhance the effects of RNAi. White boxes indicate the light phase and black boxes indicate the dark phase. Gray shades indicate DD. G4, GAL4; U, UAS.",
    "ncbi_link": "dcr2: 36993
Dicer2: 36993
G4: 855828
GAL4: 855828"
  },
  {
    "caption": "B-D The period of DD locomotor rhythms of flies with Nipped-A knocked down and controls. Data information: (B-H) Error bars represent standard error of the mean (SEM). Digits on the bars are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using One-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###P<0.001, * compared with the GAL4 controls; # compared with the UAS controls. White bar indicates UAS or GAL4 controls. Gray bar indicates flies with Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483"
  },
  {
    "caption": "E, F Using temperature-sensitive GAL80 system to control Nipped-A RNAi expression. (E) The period of DD locomotor rhythms of flies raised at 18ºC and tested at 29ºC. (F) The period of DD locomotor rhythms of flies raised at 29ºC and tested at 18ºC. Data information: (B-H) Error bars represent standard error of the mean (SEM). Digits on the bars are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using One-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###P<0.001, * compared with the GAL4 controls; # compared with the UAS controls. White bar indicates UAS or GAL4 controls. Gray bar indicates flies with Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
GAL80: 854954
Nipped-A: 35483"
  },
  {
    "caption": "G, H The period of DD locomotor rhythms of flies treated with RU486 to activate the pdfG4-geneswitch (pdf-GS) driver (G) or vehicle control (H). Data information: (B-H) Error bars represent standard error of the mean (SEM). Digits on the bars are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using One-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###P<0.001, * compared with the GAL4 controls; # compared with the UAS controls. White bar indicates UAS or GAL4 controls. Gray bar indicates flies with Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
pdf: 43193"
  },
  {
    "caption": "A Plots of relative mRNA abundance vs circadian time (CT) for clock genes determined by qRT-PCR in whole head extracts of Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1/+) and control (timG4/+;Udcr2/+) collected on DD1 (tim/cry, n=5; Pdp1ε/per/clk/cyc, n=3; vri, n=6). For each time series, the value of the lowest time point was set to 1.",
    "ncbi_link": "clk: 38872
cry: 42305
cyc: 40162
dcr2: 36993
G4: 855828
Nipped-A: 35483
Pdp1ε: 45588
per: 31251
tim: 33571
vri: 33759"
  },
  {
    "caption": "B Western blots of proteins from whole head extracts of Nipped-A RNAi and control flies collected on DD1 and probed with TIM, PDP1ε and PER antibodies. C Quantification of TIM (n=5), PDP1ε (n=3) and PER (n=3) protein levels of blots in (B). TIM, PDP1ε and PER protein levels were normalized to that of HSP70. For each time series, the value of the control at the peak time point was set to 1. ",
    "ncbi_link": "Nipped-A: 35483"
  },
  {
    "caption": "D Brains from Udcr2/+;cryG4-16/+ and Udcr2/+;cryG4-16/UNipped-ARNAi flies collected at CT0, 4, 8, 12, 16, 20 on DD1 were immunostained with TIM (green) , PDP1ε (red), PER (green) and PDF (red or green) antisera. The scale bar represents 10µm. E Quantification of TIM, PDP1ε and PER protein levels in the s-LNvs of images in (D) (TIM: CT8: Udcr2/+;cryG4-16/+, n=89; Udcr2/+;cryG4-16/UNipped-ARNAi, n=58; CT20: Udcr2/+;cryG4-16/+, n=130; Udcr2/+;cryG4-16/UNipped-ARNAi, n=80; PDP1ε: CT4: Udcr2/+;cryG4-16/+, n=46; Udcr2/+;cryG4-16/UNipped- RNAi, n=26; CT16: Udcr2/+;cryG4-16/+, n=65; Udcr2/+;cryG4-16/UNipped-ARNAi, n=41; PER: CT0: Udcr2/+;cryG4-16/+, n=90; Udcr2/+;cryG4-16/UNipped-ARNAi, n=58; CT12: Udcr2/+;cryG4-16/+, n=86; Udcr2/+;cryG4-16/UNipped-ARNAi, n=64). ",
    "ncbi_link": "cry: 42305
dcr2: 36993
G4: 855828
Nipped-A: 35483"
  },
  {
    "caption": "A, B The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing tim (A) or carrying heterozygous tim01 mutation (B). Ptim is a tim cDNA construct driven by tim promoter. Data information: Error bars represent SEM. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the over-expression or mutant flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated core clock gene. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated core clock gene and Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
tim: 33571"
  },
  {
    "caption": "C, D The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing Pdp1ε (C) or carrying heterozygous Pdp1ε3135 mutation (D). Data information: Error bars represent SEM. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the over-expression or mutant flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated core clock gene. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated core clock gene and Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
Pdp1ε: 45588"
  },
  {
    "caption": "E, F The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing per (E) or carrying perL mutation (F). Data information: Error bars represent SEM. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the over-expression or mutant flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated core clock gene. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated core clock gene and Nipped-A knocked down. G4, GAL4; U, UAS.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
per: 31251"
  },
  {
    "caption": "A Plots of relative mRNA abundance of Nipped-A in whole head extracts of w1118 flies in LD and DD1 determined by qRT-PCR (n=3).",
    "ncbi_link": "Nipped-A: 35483"
  },
  {
    "caption": "B Left panel: Western blots of proteins from whole heads of w1118 and Nipped-A RNAi flies collected during LD or DD1 and probed with NIPPED-A antibody. Right panel: quantification of NIPPED-A protein levels of blots in the left panel (LD, n=3; DD1, n=5).",
    "ncbi_link": "Nipped-A: 35483"
  },
  {
    "caption": "C Chromatin immunoprecipitation (ChIP) assays to detect NIPPED-A binding at E-box, transcription start site (TSS) and gene body of tim, Pdp1ε and per using w1118 flies (n=3). Data information: Error bars represent SEM. Two-way ANOVA, significant effect between NIPPED-A and IgG were found for tim E-box (P<0.001), Pdp1ε E-box (P<0.001), per E-box (P<0.001), tim TSS (P<0.001), Pdp1ε TSS (P<0.001), per TSS (P<0.001), tim gene body (P<0.001), Pdp1ε gene body and per gene body (P<0.001). Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. G4, GAL4; U, UAS.",
    "ncbi_link": "GAL4: 855828
Pdp1ε: 45588
per: 31251
tim: 33571"
  },
  {
    "caption": "A Plots of relative pre-mRNA abundance of tim (n=5) and Pdp1ε (n=3) determined by qRT-PCR in the whole head extracts of Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1) and control (timG4/+;Udcr2/+) flies during DD1.",
    "ncbi_link": "dcr2: 36993
G4: 855828
Nipped-A: 35483
Pdp1ε: 45588
tim: 33571"
  },
  {
    "caption": "B ChIP assays to detect ub-H2B binding at E-box, TSS and gene body of tim, Pdp1ε, per and clk in Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1) and control (timG4/+;Udcr2/+) (n≥3). Data information: Student's t-test, *P < 0.05. Two-way ANOVA, significant effect between ub-H2B and IgG were found for all genomic regions tested (P<0.001). Significant effect of genotypes were found for tim E-box (P<0.05), Pdp1ε E-box (P<0.01), tim TSS (P<0.01) and Pdp1ε TSS (P<0.001).",
    "ncbi_link": "clk: 38872
dcr2: 36993
G4: 855828
Nipped-A: 35483
Pdp1ε: 45588
per: 31251
tim: 33571"
  },
  {
    "caption": "A, B The period (A) and power (B) of DD locomotor rhythms of flies with not knocked down and controls. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the not overexpression flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated not. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated not and Nipped-A knocked down.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
not: 40030"
  },
  {
    "caption": "C Plots of relative mRNA abundance vs CT for clock genes determined by qRT-PCR in whole head extracts of not RNAi (timG4/+;Udcr2/UnotRNAi) and control (timG4/+;Udcr2/+) collected on DD1 (n=5).",
    "ncbi_link": "dcr2: 36993
G4: 855828
not: 40030
tim: 33571"
  },
  {
    "caption": "D ChIP assays to detect ub-H2B binding at E-box, TSS and gene body of tim and Pdp1ε in not RNAi (timG4/+;Udcr2/UnotRNAi) and control (timG4/+;Udcr2/+) (n=3). Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. Statistical difference is measured using two-way ANOVA, P<0.001, significant effect of genotypes were found for tim E-box (P<0.01), Pdp1ε E-box (P<0.05), tim TSS (P<0.05) and Pdp1ε TSS (P<0.001) and tim gene body (P<0.01). G4, GAL4; U, UAS.",
    "ncbi_link": "dcr2: 36993
G4: 855828
GAL4: 855828
not: 40030
Pdp1ε: 45588
tim: 33571"
  },
  {
    "caption": "E, F The period of DD locomotor rhythm of flies when knocking down Nipped-A and over-expressing not. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the not overexpression flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated not. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated not and Nipped-A knocked down.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
not: 40030"
  },
  {
    "caption": "G The period of DD locomotor rhythm of flies co-expressing Nipped-A RNAi and not RNAi. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the not overexpression flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated not. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated not and Nipped-A knocked down.",
    "ncbi_link": "G4: 855828
GAL4: 855828
Nipped-A: 35483
not: 40030"
  },
  {
    "caption": "A Number of differentially up- and down-regulated genes (DEG) in RNAi-ASCO1 seedlings as compared to wild type (WT) according to the RNA-seq data (FDR < 0.01, |log2FC| >= 0.75). B Fraction of DEG found in each transcript class as defined in the Araport11 gene annotation. AS stands for antisense.",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": " D Representative picture of 14-day-old plants grown 9 days in liquid 1/2MS supplemented with 1 µM flg22. The scale bar representing 0.6cm is included in the picture. E Lateral root density of WT and two independent RNAi-ASCO lines 9 days after transfer in 1/2MS supplemented with 0.1 µM or 1 µM flg22. ",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": " F Representative picture of root apical meristems after cell wall staining, in response to flg22. TZ: Transition Zone; QC: Quiescent Center. G Root apical meristem size of WT and RNAi-ASCO1 (eg distance from QC to TZ in µm). ",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": "B Number of genes containing at least one differential RNA processing event (as defined by RNAprof p.adj < 0.001) in CDS, introns, 5'UTR and 3'UTR between RNAi-ASCO1 and WT. Up and Down fractions correspond to increase or decrease, respectively, of RNA-seq coverage in RNAi-ASCO1 for each specified gene feature.",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": " B Scatter plot showing the respective gene expression fold change in RNAi-ASCO and 35S:ASCO lines as compared to WT. Genes showing significant changes in RNAi-ASCO and 35S:ASCO are highlighted as yellow and blue dots, respectively. ",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": " C Scatter plots showing the respective Percent Spliced In difference (dPSI) in RNAi-ASCO and 35S:ASCO lines as compared to WT. Genes showing significant changes in RNAi-ASCO, 35S:ASCO or in both lines are highlighted as red, green or blue dot, respectively. Gray dots represent all AS events. ",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": " Analyses of RT-PCR products of SR34 transcripts on 8% acrylamide gel. Quantification of the ratio of SR34 isoforms detected in the gel in (B) RNAs were extracted from WT and RNAi-ASCO1 14-day-old plants. The asterisk (*) indicates a significant difference as determined by Student's T test (p < 0.05, n = 3 biological replicates). Error bars show mean +/- standard deviation. ",
    "ncbi_link": "ASCO: 6240510
SR34: 839262"
  },
  {
    "caption": " Analyses of RT-PCR products of NUDT7 transcripts on 8% acrylamide gel. Quantification of the ratio of NUDT7 isoforms detected in the gel in (E) respectively. RNAs were extracted from WT and RNAi-ASCO1 14-day-old plants. The asterisk (*) indicates a significant difference as determined by Student's T test (p < 0.05, n = 3 biological replicates). Error bars show mean +/- standard deviation. ",
    "ncbi_link": "ASCO: 6240510
NUDT7: 826884"
  },
  {
    "caption": " A Analysis of ASCO enrichment by ChIRP using two sets of independent biotinylated probes ODD and EVEN compared to negative control with probes designed against the LacZ RNA. The fold enrichment was calculated between ODD or EVEN samples against LacZ. These samples were used for protein precipitation and Mass Spectrometry analyses (ChIRP-MS), from which PRP8a was identified as a potential ASCO partner. ",
    "ncbi_link": "LacZ: 
ASCO: 6240510"
  },
  {
    "caption": " B Validation of PRP8a-ASCO interaction by PRP8a-RIP. U5 RNA was used as a positive control. Data information: In , the results are expressed as a percentage of the Input for PRP8a RIP followed by RT-qPCR ",
    "ncbi_link": "ASCO: 6240510
U5: 836235"
  },
  {
    "caption": " A ASCO transcript levels in WT and prp8-7 mutants. ",
    "ncbi_link": "ASCO: 6240510
prp8: 844347"
  },
  {
    "caption": "prp8-7 leaky mutant displays similar AS events as observed in RNAi-ASCO. Quantification of SR34 isoforms splicing index by RT-qPCR.",
    "ncbi_link": "ASCO: 6240510
SR34: 839262
prp8: 844347"
  },
  {
    "caption": " C prp8-7 leaky mutant displays similar AS events as observed in RNAi-ASCO. Quantification of ESP isoforms splicing index by RT-qPCR. ",
    "ncbi_link": "ASCO: 6240510
ESP: 841842
prp8: 844347"
  },
  {
    "caption": " D ASCO transcript levels in smd1b mutant. In A and D RNAs were extracted from WT, prp8-7 and smd1b 14-day-old plants. ",
    "ncbi_link": "ASCO: 6240510
smd1b: 828163
prp8: 844347"
  },
  {
    "caption": " E SmD1b can bind ASCO in vivo. U6 RNA was used as a positive control and a housekeeping gene (HKG2, AT4G26410) RNA as a negative control. ",
    "ncbi_link": "ASCO: 6240510
AT4G26410: 828747
U6: 835191
HKG2: 833552"
  },
  {
    "caption": " F SmD1b recognizes in vivo the RNAs of 4 genes regulated by ASCO. In E and F the results were expressed as % INPUT in SmD1b-GFP RIP and IgG RIP used as a negative control. ",
    "ncbi_link": "ASCO: 6240510"
  },
  {
    "caption": "smd1b mutant displays similar AS events as observed in RNAi-ASCO. Quantification of SR34 isoforms splicing index by RT-qPCR.",
    "ncbi_link": "ASCO: 6240510
smd1b: 828163
SR34: 839262"
  },
  {
    "caption": " H smd1b mutant displays similar AS events as observed in RNAi-ASCO. Quantification of ESP isoforms splicing index by RT-qPCR. ",
    "ncbi_link": "ASCO: 6240510
smd1b: 828163
ESP: 841842"
  },
  {
    "caption": "E. The endouc and ela3l (negative control) mRNAs were separately microinjected into zebrafish embryos from huORFZ at a one-cell stage. Upper panels: observation of GFP signal expressed in huORFZ embryos at 72 hpf. Lower panels: magnification of pictures corresponding to the upper panels.",
    "ncbi_link": "ela3l: 554107
endouc: 562040"
  },
  {
    "caption": "D, E. The cleavage activity of Endouc was studied using materials presented at each lane. EndoucK242A: Endouc mutant; Extract: incubated in cell extracts; and Buf: reaction buffer. RNA probe without adding reaction buffer served as a negative control. The predicted cleavage sites (U) were mutated to generate mutant huORFchop transcript (unlabelled huORF-mt) and labelled by biotin (biotin-huORF-mt). Unlabelled competitor RNA was added in reactions at five times higher than that of the biotinylated probe.",
    "ncbi_link": "Endouc: 562040"
  },
  {
    "caption": "A. HEK 293T cells were transfected with pCS2 vector (black), pCS2-Endouc (red), and pCS2-EndoucK242A (green) for 24 hr and subjected to either DMSO (control) or thapsigargin (TH; stress) treatment for 1 hr. The lysates of transfected cells were applied to polysome profile analysis (PPA). The sucrose gradient from top to bottom was shown from left to right, respectively. The sedimentation of 40S, 60S, 80S, and polysomes was indicated. Lysate from control, Endouc-expressing, and EndoucK242A-expressing cells were applied to PPA. The resulting fractions were TCA-precipitated, analysed by SDS-PAGE, and subjected to Western blot using antibodies against Flag and S6.",
    "ncbi_link": "Endouc: 562040"
  },
  {
    "caption": "B. The luc activity of Fluc (solid column) versus Rluc (blank column) in HEK 293T cells transfected with bicistronic mRNAs shown in Figures A was presented as an increase in fold over that obtained from control group of RF which was normalized as 1. These data suggested that the change of Fluc/Rluc ratio shown in Figures A was entirely dependent on the change of Fluc activity. The data were averaged from three independent experiments and presented as mean ± S.D. (n = 3). Student's t test was used to determine significant differences between each group (**: P<0.005).",
    "ncbi_link": "Fluc: 
luc: "
  },
  {
    "caption": "D. The luc activity of Fluc (solid column) versus Rluc (blank column) in HEK 293T cells transfected with bicistronic mRNAs shown in Figures C was presented as an increase in fold over that obtained from control group of hpRF which was normalized as 1. These data suggested that the change of Fluc/Rluc ratio shown in Figures C was entirely dependent on the change of Fluc activity. The data were averaged from three independent experiments and presented as mean ± S.D. (n = 3). Student's t test was used to determine significant differences between each group (***: P <0.001).",
    "ncbi_link": "Fluc: 
luc: "
  },
  {
    "caption": "A-F. Schematic representation of capped (m7G-capped) and A-capped (non-functional capped) monocistronic mRNAs with poly(A)-tail-encoded firefly luciferase (Fluc) and fused upstream with (A) c-myc IRES, (B) no insertion, (C) non-specific 105-nt luc RNA (Non105), (D) huORFchop-1-105-nt, (E) huORFchop-69-105-nt, and (F) huORFchop-81-105-nt as shown above each bar graph. The RNA transfection assay of each transcript equipped with m7G-capped or A-capped monocistronic mRNA in HEK 293T cells was compared. To normalize the luc activities of capped and A-capped Fluc transcripts, the m7G-capped Renilla luc (Rluc) mRNA was used as an internal control. The luc activity of cells transfected with Cap-monocistronic mRNA in each graph was set as 100%.",
    "ncbi_link": "Fluc: 
luc: 
luciferase: 
chop: 561924
c-myc: 4609"
  },
  {
    "caption": "GFP expression under Pdgfrb-promoter in mice is present in mesangial cells of glomeruli and interstitial cells of cortex and medulla, but not in tubular cells. Nuclei are stained with DAPI (blue). Scale bar = 50 µm",
    "ncbi_link": "Pdgfrb: 18596"
  },
  {
    "caption": "Tissue clearing with Scale and 3D reconstruction of Pdgfrb-GFP reporter mice in a healthy and fibrotic kidney (UUO day 5) shows the expansion of Pdgfrb expressing cells in fibrosis.",
    "ncbi_link": "GFP: 
Pdgfrb: "
  },
  {
    "caption": "Representative Ki67 immunofluorescence staining (green) in wt and Foxd1Cre::Pdgfrb+/J mice, showing increased proliferation in the transgenic mice. Glomeruli are outlined with circles, arrowheads point to Ki67 positive interstitial cells. Nuclei are stained with DAPI (blue). Scale bar = 50 µm.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Quantification of proliferating Ki67-positive cells specifically in glomeruli (C), interstitium (D) and tubules (E) in Foxd1Cre::Pdgfrb+/J mice (black bars) and wt mice (white bars) of 6, 14, 25 and 35 weeks of age. Foxd1Cre::Pdgfrb+/J mice exhibited increased proliferation of glomerular and interstitial cells, whereas tubular epithelial cell proliferation was not altered. Data in C, D and E are shown as means ± SD of n = 3 animals per group.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "FoxD1-reporter mice (Foxd1::tdTomato) confirmed the expansion of mesenchymal cells in 14 weeks old Foxd1Cre::Pdgfrb+/J mice both in glomeruli and interstitium. Circles outline glomeruli. Scale bar = 50 µm. Quantification of FoxD1-Tomato positive cells in the cortical interstitium in 14 weeks old Foxd1Cre::Pdgfrb+/J and wt mice confirmed the significantly increased expansion of mesenchymal cells by 42% in Foxd1Cre::Pdgfrb+/J mice. Cells were counted in six viewfields at 40x magnification. Bar graphs show means ± SD of n = 3 mice per group.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
FoxD1: 15229
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Isolated primary fibroblasts and mesangial cells from Foxd1Cre::Pdgfrb+/J mice have higher proliferation rates assessed by bromodeoxyuridine (BrdU) incorporation assay compared to cells from wt mice. Bar graphs show means ± SD, n = 4 per group, *: p≤0.05 compared to wt of same time point.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "PAS staining of glomeruli of 25 weeks old wt and of 6 and 35 weeks old Foxd1Cre::Pdgfrb+/J mice shows pathological changes of the glomeruli in Foxd1Cre::Pdgfrb+/J mice. Glomerular tuft size of Foxd1Cre::Pdgfrb+/J mice was significantly increased compared to wt mice during the time course.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Immunhistological staining of collagen I and its histomorphometric quantification (F) shows that collagen I deposits in an increasing manner in Foxd1Cre::Pdgfrb+/J mice during the time course.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Histological stainings and its histomorphometric quantification (B) of kidney cortex for α-SMA of wt (25 weeks) and Foxd1Cre::Pdgfrb+/J mice of an age of 6 and 35 weeks show expansion of myofibroblasts in the interstitium of the transgenic mice.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "The tubular stress marker Lipocalin-2 (LCN2) is not expressed in early time points but increases in time course in late stages when fibrosis is more prominent and mRNA level",
    "ncbi_link": "LCN2: 16819
Lipocalin-2: 16819"
  },
  {
    "caption": "Creatinine clearance was measured in mice of an age of 10, 14, 25 and 35 weeks and decreased continuously in Foxd1Cre::Pdgfrb+/J mice, with a predicted complete loss of renal function 62 weeks in transgenic mice using linear regression analyses as described previously (Steiger et al, 2018). 10 weeks n = 5 wt and n = 4 Foxd1Cre::Pdgfrb+/J, 14 weeks n = 2 per group, 25 weeks n = 8 wt and n = 8 Foxd1Cre::Pdgfrb+/J, 35 weeks n = 3 per group ",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "The blood urea nitrogen (BUN) concentrations were higher in Foxd1Cre::Pdgfrb+/J mice compared to wt mice, apart from 25 weeks old group. Bar graphs show means ± SD, 10 weeks n = 7 wt and n = 5 Foxd1Cre::Pdgfrb+/J, 14 weeks n = 3 per group, 25 weeks n = 11 wt and n = 12 Foxd1Cre::Pdgfrb+/J, 35 weeks n = 3 per group",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Erythrocyte numbers in Foxd1Cre::Pdgfrb+/J mice continuously. Horizontal lines are means ± SD of n = 3 per group. *: p≤0.05 compared to same wt of same time point.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "hematocrit in Foxd1Cre::Pdgfrb+/J mice continuously. Horizontal lines are means ± SD of n = 3 per group. *: p≤0.05 compared to same wt of same time point.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "hemoglobin content (C) decrease in Foxd1Cre::Pdgfrb+/J mice continuously. Horizontal lines are means ± SD of n = 3 per group. *: p≤0.05 compared to same wt of same time point.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "RNA in-situ hybridization (RNAScope) of Epo (green) and Pdgfrb (purple) in renal kidney cortex of 35 week old mice shows that EPO-producing cells co-express Pdgfrb. Foxd1Cre::Pdgfrb+/J mice have less EPO-producing cells (arrows) than wt mice.",
    "ncbi_link": "Cre: 2777477
Epo: 13856
EPO: 13856
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "After induction of anemia by blood taking, the erythrocyte numbers recovered after one week in wt mice, whereas Foxd1Cre::Pdgfrb+/J mice were not able to recover their erythrocytes numbers at all. Data are means ± SD of n = 5 per group.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Five days after the induction of unilateral ureteral obstruction (UUO), a model of obstructive nephropathy and interstitial fibrosis, we assessed fibrosis (collagen I, α-SMA) and inflammation (F4/80), the classical read-out parameters in this model. Compared to wt mice with UUO, Foxd1Cre::Pdgfrb+/J mice developed significantly stronger fibrosis and inflammation (A). Representative pictures of the histological stainings are shown in (B). Scale bar = 50 µm All data in A and B show means ±SD, wt n = 4, Foxd1Cre::Pdgfrb+/J n = 3. *: p≤0.05 compared to wt",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Angiotensin II infusion via an osmotic pump induced hypertension similarly in wt and Foxd1Cre::Pdgfrb+/J mice (C).",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "In this model of hypertensive injury, the kidney function and even the histopathology was largely unaffected in wt mice, whereas the Foxd1Cre::Pdgfrb+/J mice showed a significantly increased BUN values and prominent glomerulopathy after 28 days compared to the starting values (day 0), to wt animals after 28 days and to age-matched Foxd1Cre::Pdgfrb+/J mice without Angiotensin II infusion (D).",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Consistently the creatinine clearance per g bodyweight decreased in the hypertensive Foxd1Cre::Pdgfrb+/J mice (E).",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "PAS staining showed more prominent mesangial expansion and intratubular protein casts indicative of proteinuria only in hypertensive Foxd1Cre::Pdgfrb+/J mice.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Hypertension did not induce mesangial expansion and activation in wt mice, but led to a significant increase in hypertensive Foxd1Cre::Pdgfrb+/J mice as visualized by α-SMA staining. (H) Histomorphometric analysis of α-SMA positive percentage of the glomerular tuft area.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Histomorphometric quantifications showed a significant reduction of α-SMA abundance in the glomerular tufts of imatinib treated Foxd1Cre::Pdgfrb+/J mice.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Glomerular cellularity evaluated by counting the total number of cells per glomerular tuft, normalized to the area, were significantly reduced in imatinib treated Foxd1Cre::Pdgfrb+/J mice compared to control mice.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Histomorphometric quantifications of collagen I showed no effect of imatinib treatment on mesangial sclerosis in the glomeruli (K), whereas reduced interstitial fibrosis in imatinib treated Foxd1Cre::Pdgfrb+/J mice compared to controls was found (L).",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Hemoglobin serum levels were significantly improved in imatinib treated mice.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Representative pictures of the histological stainings of α-SMA (left) and collagen I (middle: glomeruli, right: cortical interstitium). Scale bar = 50 µm",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "22 weeks old Foxd1Cre::Pdgfrb+/J mice were treated with imatinib (daily gavage, 50mg/kg bodyweight for 21 days; Foxd1Cre::Pdgfrb+/J + imatinib) and were compared to control Foxd1Cre::Pdgfrb+/J mice receiving vehicle (water; Foxd1Cre::Pdgfrb+/J + water). Aged-matched wt mice are indicated as dashed lines. Total PDGFR-β protein levels were decreased in Foxd1Cre::Pdgfrb+/J mice after imatinib treatment, as shown using western blot (O) and its densitometric evaluation (P).",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Gene expression arrays were performed in 6 week old Foxd1Cre::Pdgfrb+/J mice compared to wt mice. Listed are genes with log2 fold changes higher or lower than 0.6. Out of these 46 genes, 17 are IFN-regulated genes, 5 are involved in autophagy and 5 in matrix remodeling and fibrosis. Same genes were analysed in microdissected glomeruli (G) and tubulointerstitium (T) of patients with diabetic (DN, G: n=14, T: n=18), hypertensive (HT, G: n=15, T: n=21) nephropathy and living donors (LD, G: n=42, T: n=42) as controls, revealing a similar expression profile.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Heatmap depicting pathway activities in Foxd1Cre::Pdgfrb+/J mice and human CKD patients according to PROGENy.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "Based on the gene array datasets transcription factor activities were estimated by using DoRothEA. Depicted are the most regulated ones regulated both in Foxd1Cre::Pdgfrb+/J mice and in human CKD patients.",
    "ncbi_link": "Cre: 2777477
Foxd1: 15229
Pdgfrb: 18596"
  },
  {
    "caption": "(a) Miz1ΔPOZNes mice move slowly and lack motor coordination. The panel shows the average speed of movement and time on a rotarod (maximum: 300 s) maintained at constant speed of control and age-matched Miz1ΔPOZNes mice. The average age of mice tested was 16 months. P-values were calculated using an unpaired two-tailed Student's t-test (the number of animals tested is shown below each graph).",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(b) Defect of cerebellar growth in Miz1ΔPOZNes mice. The panels show sagittal sections of brains of control and Miz1ΔPOZNes mice at the indicated age. Dotted lines show the circumference of the cerebellum. For each mouse, the cerebellar surface area was determined; numbers show the ratio between control and Miz1ΔPOZNes mice. The number of mice analysed for each genotype is indicated on the right. Scale bar, 1 mm.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(c,d) Histology of the cerebellum. Sections of the cerebellum of 11-month-old control (c) and Miz1ΔPOZNes (d, please note different scale) mice were stained with antibodies directed against calbindin, a marker for PCs, and glial fibrillary acid protein (GFAP), a marker for Bergman glial cells. Boxes indicate the area of a detail picture in the overviews. GFAP staining is shown for adjacent section (arrowheads: regions of missing PCs). Scale bar, 500 μm (upper panels) and 100 μm (lower panels).",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(e) Enhanced apoptosis in the granular layer of cerebella in Miz1ΔPOZNes mice. The upper panel shows representative TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining of cerebella of age-matched control and Miz1ΔPOZNes mice. The lower panel shows a quantification of staining observed in four control and five Miz1ΔPOZNes mice. Error bars show s.e.m. P-value was calculated using an unpaired two-tailed Student's t-test.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(a) ISH documenting the expression of Miz1 mRNA in PCs of the cerebellum in wild-type mice. Left panel shows ISH, right panel shows haematoxylin and eosin staining. Scale bar, 50 μm. (b) IHC documenting the presence of Miz1 in the nuclei of PCs. The panel on the left shows staining with α Miz1 (H190) antibody, staining on the right is a control staining lacking primary antibody. Scale bar, 50 μm.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(b) Miz1 binds predominantly to core promoters. The panel shows a histogram of the percentage of promoters with the indicated distances between the peak of the Miz1-binding site and the next TSS. Of all the peaks, 140/261 (54%) are located in core promoters (±1.5 kb).",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(c) Miz1 binding is conserved across different cell types and species. The plot shows a Venn diagram documenting the overlap in Miz1-bound promoters between murine NPCs and human MDA-MB231 cells (a mammary epithelial tumour cell line). The P-value was calculated using a hypergeometric test. Note that different α-Miz1 antibodies (H190 and G18) were used for the analysis of mouse and human Miz1-binding sites.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(e) Electrophoretic mobility shift assay documenting binding of Miz1 to the conserved sequence element ('Miz1-binding motif'). Nuclear extracts from control HeLa cells ('Mock') or cells ectopically expressing Miz1 were incubated with radioactive oligonucleotides spanning the Miz1-binding motif of the Ambra1 and Vps28 promoters. Where indicated, binding reactions included a 25-fold excess of non-labelled oligonucleotides ('Competitor'), the indicated mutants thereof or of an oligonucleotide containing an E-box sequence from the Ubap2 promoter. Supershift assays were performed using α-Miz1 (H190, G18 and C19), α-Myc (N262) or control antibodies. *Non-specific band. The sequences of the oligonucleotides used are shown above the panel; mutated nucleotides are shown in bold.",
    "ncbi_link": "Ambra1: 55626
Ubap2: 55833
Vps28: 51160"
  },
  {
    "caption": "(a) Miz1 activates the Rorc and Ambra1 promoters, and the POZ domain is required for activation. HEK293 cells were transiently transfected with plasmids containing promoter sequences of Ambra1 or Rorc in front of luciferase and with expression vectors encoding Miz1 or MizΔPOZ. Empty vectors were used as control. Values were normalized with CMV-βGal. Error bars are s.d. of biological triplicates.",
    "ncbi_link": "luciferase: 
βGal: 
Ambra1: 55626
Rorc: 6097
Miz1: 7709"
  },
  {
    "caption": "(b) Direct target genes of Miz1 are downregulated in cerebella of Miz1ΔPOZNes mice. Microarray analysis was performed from cerebella of mice at the indicated ages. The panels show box plots (line: median, box: 50% of data points, whisker: 1.5 interquantile range, outliers are not shown) of relative gene expression (plotted as log2-fold change) of the 140 Miz1 direct target genes comparing control and Miz1ΔPOZNes mice. The P-value was calculated using a Mann-Whitney-Wilcoxon test. Microarrays were performed as technical duplicates from RNA pooled from two animals for each genotype.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(d) qRT-PCR documenting the expression of selected Miz1 target genes in cerebella of control and of Miz1ΔPOZNes mice at the indicated ages. Data represent the mean of two independent biological experiments each with three technical replicates. Error bars are s.e.m.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(a,b) Immunostaining using an α-ubiquitin antibody of (a) PCs and (b) the molecular layer of Miz1ΔPOZNes and age-matched control mice (dotted area: higher magnification). Arrowheads designate ubiquitin-positive structures. Scale bar, (a) 25 μm; (b) 50 μm.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(c) Immunofluorescence staining using an α-p62 and an α-ubiquitin antibody of the white matter of cerebella from Miz1ΔPOZNes and age-matched control mice. Nuclei were counterstained with DAPI (4',6-diamidino-2-phenylindole) and overviews of the cerebella clarifying the selected areas are shown. Scale bar, 25 μm.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(a,b) Immunostaining using an α-ubiquitin antibody of (a) PCs and (b) the molecular layer of Miz1ΔPOZNes and age-matched control mice (dotted area: higher magnification). Arrowheads designate ubiquitin-positive structures. Scale bar, (a) 25 μm; (b) 50 μm. (c) Immunofluorescence staining using an α-p62 and an α-ubiquitin antibody of the white matter of cerebella from Miz1ΔPOZNes and age-matched control mice. Nuclei were counterstained with DAPI (4',6-diamidino-2-phenylindole) and overviews of the cerebella clarifying the selected areas are shown. Scale bar, 25 μm. (d) Quantification of a, b and c. Error bars represent s.e.m. derived from the indicated numbers of animals. P-values were calculated using an unpaired two-tailed Student's t-test.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(e) Immunoblots of Triton X-100 soluble ('TX100') and insoluble ('1% SDS') fractions of cerebella obtained from control and Miz1ΔPOZNes mice of the indicated ages. Blots were probed with antibodies recognizing either mono- or polyubiquitinated proteins. Staining of the membrane with amido black was used as loading control.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(f) Transmission electron microscopy documenting the accumulation of large multilamellar bodies in PC bodies ('PC') and Purkinje dendrites ('D') of Miz1ΔPOZNes mice (N, nucleus). Such structures were not observed in age-matched control mice (as quantified in Supplementary Fig. S7b). Mean age of mice for all electron microscopy pictures is 13 monthsfor Miz1ΔPOZNes and 12.5 months for control mice. Morphologically similar structures accumulate in neurons of mice deficient in late steps of autophagy. Scale bars, 2, 0.2, 0.5 and 1 μm, respectively.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(a) Genomic PCR documenting recombination of the floxed Miz1 alleles in Cre-ER-positive and -negative MEFs. 4-OHT was added to the media for 4 days.",
    "ncbi_link": "Cre: 
ER: 13982
Miz1: 22642"
  },
  {
    "caption": "(b) qRT-PCR assays of Miz1 target genes in Miz1flox/floxCre-ER− and Miz1flox/floxCre-ER+ MEFs. The experiment was performed independently from four embryos with identical results. Error bars depict s.d. of technical triplicates from one experiment.",
    "ncbi_link": "Cre: 
ER: 13982
Miz1: 22642"
  },
  {
    "caption": "(d) qRT-PCR assays of Miz1 target genes in control and Miz1ΔPOZ MEFs after incubation in DMEM or in EBSS. Error bars depict s.d. of technical triplicates from one experiment.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(e) qRT-PCR assays documenting expression of the indicated Miz1 target genes in control and Miz1ΔPOZ neurospheres; assays were performed at passage three. s.e.m. values are derived from six biological replicates, each with technical triplicates.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(f) Recombination of Miz1flox/floxCre-ER+ neurospheres was tested by genomic PCR. 4-OHT was added to the media for 3 days.",
    "ncbi_link": "Cre: 
ER: 13982
Miz1: 22642"
  },
  {
    "caption": "(g) Immunoblots using an α-Lc3 antibody detecting Lc3-I and Lc3-II. 4-OHT-treated and non-treated Miz1flox/floxCre-ER+ neurospheres were incubated with leupeptin and ammonium chloride (lys PI) for 30 min. The expression of α-tubulin was used as loading control.",
    "ncbi_link": "Cre: 
ER: 13982
Miz1: 22642"
  },
  {
    "caption": "(h) Fluorescent microscopy of SHEP cells stably infected with lentiviruses expressing Lc3-GFP and Lamp1-RFP (to mark lysosomes). Vps28 was depleted with siRNAs and a non-targeting pool (siNTP) was used as a control. Note the accumulation of Lc3 in vesicles that do not overlap with lysosomes upon depletion of Vps28. Scale bar, 25 μm.",
    "ncbi_link": "Lamp1: 3916
Lc3: 440738///81631///84557
Vps28: 51160"
  },
  {
    "caption": "Real-time PCR analysis of cxcr4 transcript expression levels in HeLa (negative control) and in MM cell lines MM.1S and OPM-2. Shown is the mean relative expression ± SEM (n = 3 independent experiments). Values are normalized to the expression of ubiquitin (Ub). The asterisk indicates statistically significant differences (HeLa vs MM.1S: P < 0.001; HeLa vs OPM-2: P < 0.0001; Student's t-test).",
    "ncbi_link": "ubiquitin: 
cxcr4: 7852"
  },
  {
    "caption": "b, MEFs were generated from day 12.5embryos of Atg16l1 mutant mice, and western blot analysis was used to detect the a and b isoforms of ATG16L1 from whole-cell lysates",
    "ncbi_link": "Atg16l1: 77040"
  },
  {
    "caption": "c, d, Atg5-/- and ATG16L1HM MEFs were grown in the presence of the chemical inducer of autophagy rapamycin (Rap, 50 µg ml-1) and cyclohexamide (CHX, 5 µg ml-1) for 0, 4, 8 and 12 h. Cell lysates were analysed by western blot for loss of P62 expression (c). P62 levels were quantified by densitometry normalized to actin (n = 3; d). *P 0.04; **P 0.008; ***P = 0.0003",
    "ncbi_link": "ATG16L1: 77040
Atg5: 11793"
  },
  {
    "caption": "g, Detection of ATG16L1, LC3 and P62 by western blot of ileal lysates from ATG16L1HM mice. ATG16L1 can be detected in both mutant lines on longer exposures. h, i, Quantification of ATG16L1 (h) and P62 (i) normalized to actin detected in ileal lysates (n = 3). P values were calculated using two-tailed Student's t-test. Error bars, s.e.m.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "a, b, Whole-mount images taken immediately above the ileal mucosal surface from WT (a) and ATG16L1HM (b) littermate mice stained with Helix pomatia lectin that labels mucus (green) and antisera directed against lysozyme (red). Images are representative of 3 WT and 3 ATG16L1HM mice.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "c, d, Ileal sections from WT (c) and ATG16L1HM (d) mice were stained with PAS/alcian blue to detect Paneth granules by light microscopy (dashed line denotes the crypt unit and arrowheads indicate Paneth cells). Images are representative of 7 WT, 7 ATG16L1HM1 and 5 ATG16L1HM2 mice; more than 100 crypts were analysed for each",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "e, f, Representative images of indirect immunofluorescence of sections stained for lysozyme (red) in WT (e) and ATG16L1HM (f) mouse ileal crypts.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "h, i, Number of Paneth cells from ATG16L1HM (h) and Atg5flox/floxvillin-Cre (i) mice displaying each pattern of lysozyme expression (n = 6,660 cells from 5 ATG16L1HM mice and 5,634 cells from 5 WT mice; n = 1,756 cells from 2 Atg5flox/floxvillin-Cre mice and 1,649 from 2 Atg5flox/flox mice). Scale bars: a, b, 200 µm; c-f, 10 µm. *P 0.05, **P 0.01, ***P 0.001. P values were calculated using two-tailed Student's t-test. Error bars, s.e.m.",
    "ncbi_link": "ATG16L1: 77040
Atg5: 11793"
  },
  {
    "caption": "a-d, Electron micrograph of littermate WT (a, c) and ATG16L1HM (b, d) Paneth cells (for a, b, dashed lines denote individual cells, asterisk indicates normal progenitor cell; for c, d, blue stars indicate normal mitochondria in WT Paneth cells and ATG16L1HM progenitor cells, red diamonds indicate degenerating mitochondria, the dashed box shows normal Golgi compartments, and yellow asterisks indicate granules; n = 3 mice per genotype). e, Mitochondrial integrity was quantified on the basis of the percentage of the visible mitochondrial section displaying intact cisternae (n = 49 WT and 71 ATG16L1HM cells).",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "g, Chart of selected genes for which mRNA is enriched in either ATG16L1-deficient Paneth cells (baseline is WT Paneth cells) or ATG16L1-deficient thymocytes (baseline is WT thymocytes). Only haemoglobin is in common in these two sets of analyses. NS, not significant. Scale bars: a, b, 10 µm; c, d, 500 nm.",
    "ncbi_link": "ATG16L1: 77040"
  },
  {
    "caption": "a, b, Haematoxylin-and-eosin-stained sections of uninvolved areas from ileo-colic resections from patients with Crohn's disease homozygous for the safe (a) or risk (b) allele of ATG16L1 (blue dashed line denotes crypt unit).",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(A-B) Representative MA currents recorded in whole cell patch clamp experiments at -60 mV in HEK293 cells transiently transfected with Piezo2 +GABAB1+ GABAB2 + GFP (for visualization) in response to repetitive mechanical stimulation with a blunt glass probe displaced 2-5.6 µm in 0.4 μm increments every 15 s before (black) and after (red) exposure to 25 µM baclofen. Not every trace is shown for clarity.",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "(C) Quantification of normalized MA currents of HEK293 cells transfected with Piezo2+GABAB1+ GABAB2 + GFP [C, n=13, *P<0.05, **P<0.01, before (black) and after (red) baclofen treatment, Repeated measures ANOVA with student's t-test no corrections]. Data are shown as mean ± SEM.",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "(D) Quantification of MA current inactivation rate (Tau) in HEK293 cells transfected with Piezo2+GABAB1+ GABAB2 + GFP before (gray) and after (red) baclofen application (n=13, NS, not significant; Paired t-test). Data are shown as mean ± SEM and scatter plots.",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA currents of HEK293 cells transfected Piezo2 + GFP (E, n=7) before (black) and after (red) application of 25 µM baclofen. Data are shown as mean ± SEM.",
    "ncbi_link": "GFP: 
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA currents of HEK293 cells transfected Piezo2+GABAB1+ GABAB2 + βARKct-mCherry (F, n=8) before (black) and after (red) application of 25 µM baclofen. Data are shown as mean ± SEM.",
    "ncbi_link": "mCherry: 
GABAB1: 2550
GABAB2: 9568
βARKct: 25238
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA Piezo2 currents in HEK293 cells transiently transfected with Piezo2+D2RS-YFP (A, n=13) before (black) and after (red) application of quinpirole 200 nM. *P<0.05, Repeated measures ANOVA with student's t-test no corrections. Data are shown as mean ± SEM.",
    "ncbi_link": "YFP: 
D2R: 1813
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA Piezo2 currents in HEK293 cells transfected with Piezo2 and GFP (B, n=5) before (black) and after (red) application of quinpirole 200 nM. *P<0.05, Repeated measures ANOVA with student's t-test no corrections. Data are shown as mean ± SEM.",
    "ncbi_link": "GFP: 
Piezo2: 667742"
  },
  {
    "caption": "(C) Quantification of Piezo2 current inactivation rate (Tau) in HEK cells transfected with Piezo2+D2RS-YFP. Data are shown as mean ± SEM and scatter plots (n=13)",
    "ncbi_link": "YFP: 
D2R: 1813
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA Piezo2 currents in HEK293 cells transiently transfected with Piezo2+ GABAB1+ GABAB2 + GFP (A, n=12)",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA Piezo2 currents in HEK293 cells transiently transfected with Piezo2+ GABAB1+ GABAB2 + GFP (A, n=12), treated with the PI3K inhibitor Wortmannin 50 nM (B, n=10) Cells were treated with wortmannin 30 min before the experiments, and were present throughout the measurements.",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "Quantification of normalized MA Piezo2 currents in HEK293 cells transiently transfected with Piezo2+ GABAB1+ GABAB2 + GFP (A, n=12), treated with the MAPK inhibitor U0126 10 µM (C, n=7). Cells were treated with U0126 for 30 min before the experiments, and were present throughout the measurements.",
    "ncbi_link": "GFP: 
GABAB1: 2550
GABAB2: 9568
Piezo2: 667742"
  },
  {
    "caption": "CD4 T cells were pre-treated with cycloheximide  (2 μg/ml) for 2 h, then treated with cGAMP  (20 μg/ml) and αCD3/CD28 (3/28) for 4 h, then analyzed by  quantitative PCR for IFNB1  and OASL  expression. Data are depicted as mean + SEM of 3 independent donors (for cGAMP  and αCD3/CD28 treated cells without CHX  only 2 data points were obtained). Statistics were determined by a two-way ANOVA on log-transformed data using Šidák correction for multiple testing: ***p < 0.001; **p < 0.01; *p < 0.05; ns, not significant.",
    "ncbi_link": "IFNB1: 3456
OASL: 8638"
  },
  {
    "caption": "CRISPR/Cas9  targeted CD4 T cells  for the indicated genes were treated with the indicated stimuli for 48 h. Human IFNβ  levels were analyzed by ELISA. Data are depicted as mean + SEM of 3 independent donors. Statistics indicate significance by two-way ANOVA with Dunnett correction for multiple testing: ****p < 0.0001; ns, not significant.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935"
  },
  {
    "caption": "CRISPR/Cas9  targeted CD4 T cells for indicated genes were treated with the indicated stimuli for 48 h and analyzed by flow cytometry. Each panel shows propidium iodide  and  Annexin V  intensity for one representative donor out of three. Digits indicate the percentage of the parental population (single events without subcellular debris).",
    "ncbi_link": "CRISPR: 
Cas9: 69900935"
  },
  {
    "caption": "(A) α-Synuclein, CSPα, VAMP2 and SNAP-25 were immunoblotted in total brain homogenates and/or synaptosomal fractions of 1.5 month-old WT (CSPα+/+/α-syn+/+), CSPα-/-, CSPα+/-, α-syn-/-, α-syn+/- and CSPα+/-/α-syn+/-. Synapsin-1 was also blotted as a control. Quantitation of WB in synaptosomal samples was shown.",
    "ncbi_link": "CSPα: 13002
α-syn: 20617"
  },
  {
    "caption": "(D) Extracellular recordings (fEPSPs) in hippocampal brain slices from 1.5 months-old WT (CSPα+/+/α-syn+/+) and CSPα+/-/α-syn+/- mice. The left panel shows representative fEPSP traces. Summary graphs show the fEPSPs slope as a function of either the applied stimulus intensity or the prevolley amplitude. Data are the average of the values from 5 slices (from 4 mice) in the WT group and 5 slices (from 4 mice) in the CSPα+/-/α-syn+/-. *p<0.05, repeated measure ANOVA.",
    "ncbi_link": "CSPα: 13002
α-syn: 20617"
  },
  {
    "caption": "(A) Anti-myc immunostaining in different brain regions derived from 10-months-old MPS-IIIA mice intraventricularly injected with AAV2/9 vectors encoding CSPα under Synapsin-1 promoter (MPS-IIIA-myc-CSPα experimental group). As a control immunostaining was performed in brain sections from 10-months-old MPS-IIIA mice injected with empty AAV2/9 vectors (MPS-IIIA-empty experimental groups). To evaluate co-localization between exogenous CSPα and presynaptic compartment brain sections were also co-stained with anti-myc and anti-synapsin1 antibodies (confocal images are also shown).",
    "ncbi_link": "Synapsin-1: 20964"
  },
  {
    "caption": "(B) Anti-myc WB in synaptosomal fractions derived from MPS-IIIA-myc-CSPα mice. As a control WB was performed in samples from 10-months-old WT and MPS-IIIA mice injected with empty AAV2/9 vectors (WT-empty and MPS-IIIA-empty experimental groups). Synaptosomal fractions were also blotted with anti-CSPα.",
    "ncbi_link": "CSPα: 13002"
  },
  {
    "caption": "(A) EM analysis of cortical and hippocampal synapsis derived from the three experimental groups of mice. Synaptic vesicles number per synapse was quantified from ~40 different images (taken from 5 mice for each group), normalized by the length of synaptic cleft and expressed as % of WT. The synaptic density was measured from 20 different images (taken from 5 mice for each group) as the number of synapses/area(#/500μm2) and expressed as % of WT. Arrows indicate the synaptic cleft while asterisks indicate abnormal vacuoles. Values are means ± s.e.m. *P<0.05, Student's t-test: Either MPS-IIIA-empty or MPS-IIIA-myc-CSPα vs WT-empty. Scale bar: 0.2 µm",
    "ncbi_link": "CSPα: 13002"
  },
  {
    "caption": "(B) Extracellular recordings (fEPSPs) in hippocampal brain slices from WT-empty (n=8), MPS-IIIA-empty (n=5) and MPS-IIIA-myc-CSPα mice (n=5). The upper panel shows representative fEPSP traces. Summary graph shows the fEPSPs slope as a function of the applied stimulus intensity. Data are means ± s.e.m.; *P < 0.05 (WT-empty vs MPS-IIIA-empty), #P < 0.05 (MPS-IIIA-myc-CSPα vs. MPS-IIIA-empty), Kruskal-Wallis ANOVA followed by Dunn's test.",
    "ncbi_link": "CSPα: 13002"
  },
  {
    "caption": "(C) Mean distance travelled, maximal speed, immobility time and line crossing during 10 min testing in the open field, divided into 5 minute intervals in WT-empty, MPS-IIIA-empty and MPS-IIIA-myc-CSPα female mice (n=9, n=9, n=7 respectively). Distance, percentage open entries and open time in the elevated plus maze and latency to fall off the wire (*body weight) in the wire hanging test in WT-empty, MPS-IIIA-empty and MPS-IIIA-myc-CSPα male mice (n=10, n=8, n=9 respectively). Values are means ± s.e.m; *P < 0.05 (MPS-IIIA-empty vs. WT-empty), #P < 0.05 (MPS-IIIA-myc-CSPα vs. MPS-IIIA-empty), two-way ANOVA for repeated measures for open field measures and t-test for the plus maze and the wire hanging followed by Duncan post-hoc test. Animals' average age was 28±2 weeks.",
    "ncbi_link": "CSPα: 13002"
  },
  {
    "caption": "(E) Kaplan-Meier survival analysis in WT-empty (n=13), MPS-IIIA-empty (n=13) and MPS-IIIA-myc-CSPα (n=13) male mice. The Kaplan-Meier survival curve was analyzed with the Chi-square test. A P value <0.05 was considered to be statistically significant. P= 0.00003 (MPS-IIIA-empty vs WT-empty), P= 0.000776 (MPS-IIIA-myc-CSPα vs MPS-IIIA-empty).",
    "ncbi_link": "CSPα: 13002"
  },
  {
    "caption": "(B-C) Immunofluorescent (IF) staining of Pax7 and YY1 was performed on cryosections of myotome or limb bud from Ctrl or YY1cKO mice to confirm the ablation of YY1 in Pax7 expressing progenitors. Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(D) Representative images of Ctrl, Heterozygous (Het) and YY1cKO newborn (P0) mice or embryos at E18.5 day.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(E) Excised lungs from P0 Ctrl or YY1cKO pups were placed in a beaker for sinking test. The lung from YY1cKO pup sank whereas Ctrl floated.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(F) P0 lungs were stained with Hematoxylin and Eosin (H&E) and representative images are shown. Scale bar = 100 µm. (G) Representative images of diaphragms (Dps) isolated from P0 Ctrl or YY1cKO littermates.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(K) Representative images of H&E staining of hind limb muscles isolated from Ctrl or YY1cKO embryos at E18.5 day. Scale bar = 400 µm (left) or 50 µm (right).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(B) SCs were FACS sorted 3 days after the last TM injection and cultured for 1.5 days; RT-qPCR detection of YY1 mRNA shows the ablation in YY1iKO cells.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(C) IF staining for Pax7 and YY1 on freshly isolated FISCs or (D) single myofibers from EDL muscles or (E) cryosections from TA muscles showing the deletion of YY1 protein from YY1iKO cells. Scale bar =100 µm in (C) or 50 µm in (D-E).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(F) Representative FACS plots. About 100,000 cells from 2-month-old Ctrl and YY1iKO mice were sorted by FACS 3 weeks post-TM injection. The percentage of SCs was shown. (n=3 mice, each).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(I) Left: representative images of TA muscles isolated from Ctrl or YY1iKO mice 60 days post-CTX injury. Right: Masson's Trichrome staining of the above muscles to visualize the degree of fibrosis. Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(K) Representative FACS plots showing the percentage of SCs sorted from TA muscles 3 days after CTX injury of Ctrl and YY1iKO mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(N) IF staining for Pax7 and Laminin on TA muscles 4 weeks after CTX injury of Ctrl or YY1iKO mice. Quantifications of the numbers of Pax7+ SCs per 100 fibers are shown on the right (n=3 mice, each). Scale bar = 100 μm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(P) H&E staining was performed on TA muscles of Ctrl or YY1iKO mice 7 day after second CTX injury. Scale bar = 400 μm (left) or 100 μm (right).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(S) IF staining for eMyHC and Laminin on TA muscles 7 days after the second CTX injury of Ctrl or YY1iKO mice. Quantifications of the number of eMyHC+ fibers per area are shown on the right (n=3 mice, each). Scale bar = 100 μm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(B) SCs were FACS sorted 4 months after the last TM injection; RT-qPCR detection of YY1 mRNA shows the ablation in YY1dKO cells.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(C) Representative images of Ctrl or YY1dKO mice 4 months after the TM administration.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(D) Representative images of limb muscles (Tibialis anterior, TA; Gastrocnemius, Gas; Quadruple, Quad) from Ctrl or YY1dKO mice. (E) Quantifications of muscle weight from three pairs of littermate mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(F) Representative images of Dp muscles isolated from Ctrl or YY1dKO mice 4 months after the TM injection.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(G) H&E or (H) MyHC staining was performed on TA or Dp muscles from Ctrl or YY1dKO mice. Quantifications of the numbers of MyHC+ fibers per area of TA or Dp muscles are shown on the right (n=3 mice, each). Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(I) Collagen1 or (J) Masson's Trichrome staining was performed on TA or Dp muscles from Ctrl or YY1dKO mice. Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(K) The distribution of fiber size measured by CSA in TA muscles from 3 pairs of 6-month-old Ctrl and YY1dKO mice was calculated (n=3 mice, each).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(L) Representative FACS plots showing the percentage of SCs sorted from 6-month-old Ctrl and YY1dKO mice (n=3 mice, each).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(M) IF staining for Pax7 and Laminin on TA muscles of Ctrl or YY1dKO mice. Quantifications of the numbers of Pax7+ SCs per 100 fibers are shown on the right (n=3 mice, each).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "EDL muscles from Ctrl or YY1dKO mice were subjected to measurement of maximal isometric tetanic force. Left: Representative trace images of normalized tetanic force. (Right): quantification of the force by normalizing with cross-sectional area (CSA). (n = 3 mice, each). Error bars represent s.d.'s of the mean. Student's t-test (two-sided): *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "SOL muscles from Ctrl or YY1dKO mice were subjected to measurement of maximal isometric tetanic force. Left: Representative trace images of normalized tetanic force. (Right): quantification of the force by normalizing with cross-sectional area (CSA). (n = 3 mice, each). Error bars represent s.d.'s of the mean. Student's t-test (two-sided): *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(A) FACS-isolated SCs from Pax7-nGFP mice were cultured for the designated time (0, 24, 48 or 72 hrs). YY1 expression was quantified by RT-qPCR. 18S was used as the normalization control.",
    "ncbi_link": "18S: 
YY1: 22632"
  },
  {
    "caption": "(C) An equal number of FACS-isolated SCs from Ctrl or YY1iKO mice were cultured for 48 hrs and EdU labelled for 8 hrs, followed by immunostaining for Pax7 (green) and EdU (red). Quantifications of the percentage of EdU+ cells are shown on the right (n=3 mice, each). Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(H) An equal number of FACS-isolated SCs from Ctrl or YY1iKO mice were cultured for 24hrs and EdU labeled for 12 hrs, followed by immunostaining for Pax7 (green) and EdU (red) was performed. Quantifications of the percentage of EdU+ cells are shown on the right (n=3 mice, each). Scale bar = 100 µm.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(K) FACS-isolated SCs from YY1iKO mice were infected with YY1 expressing or control viruses, followed by immunostaining for Pax7 (green) and MyoD (red) 36 hrs post-transfection. Scale bar = 100 µm. Quantifications of the numbers of each population, Pax7+MyoD-, Pax7-MyoD+, or Pax7+MyoD+, are shown on the right (n=3 mice, each).",
    "ncbi_link": "YY1: 
YY1: 22632"
  },
  {
    "caption": "(A) RNA-seq was performed with RNAs extracted from ASCs (FACS purified and cultured for 36hrs) of YY1iKO or Ctrl mice; scatter plot shows differentially expressed genes with a fold change >=2 (red dots) in YY1iKO vs Ctrl.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(C) Genomic snapshots showing the examples of mitochondrial genes (Uqcr11, Mrp11, Apo5o and Nme4) up-regulated in YY1iKO vs Ctrl cells.",
    "ncbi_link": "Apo5o: 
Mrp11: 66419
Nme4: 56520
Uqcr11: 66594
YY1: 22632"
  },
  {
    "caption": "(D) GSEA analysis shows oxidative phosphorylation gene set is enriched in YY1iKO vs Ctrl cells (p-value < 0.0001).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(E) RT-qPCR validation of the expression of the selected up-regulated mitochondrial genes in YY1iKO vs Ctrl.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(F) Protein levels of the respiratory chain complexes I-V components in YY1iKO vs Ctrl ASCs were detected using a mitoprofile antibody cocktail. β-actin was used as the loading control.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(G) RNA-seq was performed using RNAs from freshly isolated SCs (FISCs); scatter plot shows differentially expressed genes with a fold change >=2 (red dots) in YY1iKO vs Ctrl.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(I) Genomic snapshots show the selected mitochondrial genes (Cox8b, Nme4, Slc25a29, Nnt) up-regulated in YY1iKO vs Ctrl FISCs.",
    "ncbi_link": "Cox8b: 12869
Nme4: 56520
Nnt: 18115
Slc25a29: 214663
YY1: 22632"
  },
  {
    "caption": "(J) ChIPseq was performed using chromatins from WT ASCs and the genomic distribution of 2031 YY1 binding peaks is shown.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(N) Genomic snapshots of two of the above identified mitochondrial genes (Tomm40I and Ndufa13) that are bound by YY1 in their TSS (ChIPseq tracks) and up-regulated by YY1 deletion (RNAseq tracks).",
    "ncbi_link": "Ndufa13: 67184
Tomm40I: 641376
YY1: 22632"
  },
  {
    "caption": "(O) ChIP-qPCR validation of YY1 binding on some mitochondrial genes. Negative control (NC) represents a genomic region on Chromosome 11 with no YY1 binding peak identified. Enrichment fold was calculated as the amount of amplified DNA from YY1 binding sites normalized to values obtained from IgG control.",
    "ncbi_link": "IgG: 
YY1: 22632"
  },
  {
    "caption": "ChIP-qPCR was performed to show the enrichment of Ezh2 (P) binding on selected mitochondrial genes.",
    "ncbi_link": "Ezh2: 14056"
  },
  {
    "caption": "ChIP-qPCR was performed to show the enrichment of Suz12 (Q) binding on selected mitochondrial genes.",
    "ncbi_link": "Suz12: 52615"
  },
  {
    "caption": "(S) A construct to express wild type YY1(WT), or two mutants lacking DNA binding activity, YY1(1-394) and YY1(S365D) were transfected into YY1iKO cells; the expression of mitochondrial gene was measured. Error bars represent s.d.'s of the mean. Student's t-test (two-sided): N.S = non-significant, *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(D) Ctrl and YY1iKO ASCs were stained with 60 ug/mL 2-NBDG for 45 mins and the fluorescence intensity (MFI) of 2-NBDG was measured by flow cytometry (n=3 mice, each).",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "An equal number of Ctrl and YY1iKO cells were cultured for 36h; basal extracellular acidification rate (ECAR) level were measured and normalized with cell numbers. N=3 mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "An equal number of Ctrl and YY1iKO cells were cultured for 36h Lactate concentration (F) were measured and normalized with cell numbers. N=3 mice. by",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "An equal number of Ctrl and YY1iKO cells were cultured for 36h ATP production (G) were measured and normalized with cell numbers. N=3 mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(H) Genomic snapshots depict RNAseq profiles of the selected glycolytic genes (Hk2, Glut1, Ldha, Pdk1, Eno1) down-regulated in YY1iKO vs Ctrl ASCs.",
    "ncbi_link": "Eno1: 13806
Hk2: 15277
Ldha: 16828
Pdk1: 228026
Glut1: 20525
YY1: 22632"
  },
  {
    "caption": "(I) Expression of the selected glycolytic genes was quantified by RT-qPCR. Hsp90ab1 was used as the normalization control.",
    "ncbi_link": "Hsp90ab1: 15516"
  },
  {
    "caption": "(J) Re-expression of YY1 by transfecting YY1iKO ASCs with a YY1 WT expressing plasmid led to up-regulation of glycolytic genes including Glut1, Pfkl, Gapdh, Eno1, Pgam1, Pkm. Hsp90ab1 was used as the normalization control.",
    "ncbi_link": "YY1: 
Eno1: 13806
Gapdh: 14433
Hsp90ab1: 15516
Pfkl: 18641
Pgam1: 18648
Pkm: 18746
Glut1: 20525
YY1: 22632"
  },
  {
    "caption": "(K) FACS-isolated SCs from Pax7-nGFP mice were transfected with Hif1α or control siRNAs and EdU labeled for 5 hrs. The percentage of MyoD+EdU+ cells over the total number of MyoD+ cells was quantified. Scale bar = 100 µm. N=3 mice.",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "(L) The expression of glycolytic genes and cell cycle related genes was detected by RT-qPCR in the above transfected cells. β-actin was used as the normalization control.",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "(M) Hif1α protein level was detected by Western blotting in YY1iKO vs Ctrl ASCs. β-actin was used as the loading control.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(N) Left: Image of flow cytometric analysis of Hif1α protein or IgG control in YY1iKO vs Ctrl ASCs. Right: Relative mean fluorescence intensity (MFI) of Hif1α protein is shown. N=3 mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(O) YY1iKO ASCs were transfected with empty YY1 WT viruses; the relative expression level of Hif1a protein was detected by the above described flow cytometric analysis N=3 mice. Error bars represent s.d.'s of the mean. Student's t-test (two-sided): N.S = non-significant, *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "YY1: 
YY1: 22632"
  },
  {
    "caption": "(A-B) Ctrl or YY1iKO ASCs were treated with CHX (Cycloheximide) for 90 mins and Hif1α protein was measured by flow cytometry. The numbers indicate the degradation rate after CHX treatment. N=3 mice. (C) The relative degradation rate was calculated by the ratio of degradation rate in YY1iKO (11.14% ± 1.71%) vs Ctrl (5.08% ± 0.796%). N=3 mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(F) ASCs from YY1iKO mice were infected with pRlenti-Hif1α (P402A/P564A) (Hif1α-DM) viruses to overexpress a non-degradable Hif1α protein or GFP-expressing viruses. ASCs from Ctrl mice were also infected with the GFP viruses. 36 hrs after infection, the expression of target glycolytic genes was detected by RT-qPCR. Hsp90ab1 was used as the normalization control.",
    "ncbi_link": "Hif1α: 3091
Hsp90ab1: 15516
YY1: 22632"
  },
  {
    "caption": "(G) SCs were isolated from Ctrl or YY1iKO mice and infected with the above viruses. EdU labeling was then performed for 5.5 hrs. The percentage of MyoD+EdU+ cells over the total number of MyoD+ cells was quantified. Scale bar = 100 µm. N=3 mice.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "Heat maps indicating gene expression levels (Log2[FPKM]) of pentose cycle enzymes (H) in YY1iKO vs Ctrl.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "Heat maps indicating gene expression levels (Log2[FPKM]) of amino acid transporter (I) in YY1iKO vs Ctrl.",
    "ncbi_link": "YY1: 22632"
  },
  {
    "caption": "(J) YY1(WT) or YY1(S365D) mutant was expressed in YY1iKO ASCs and EdU labeled for 6 hrs. (K) Similarly, YY1 (WT) or YY1 (1-394) mutant was expressed and EdU labeled for 6hrs. A GFP expressing plasmid was used the negative control. The percentage of Pax7+/EdU+ cells over the total number of Pax7+ cells was quantified. Error bars represent s.d.'s of the mean. Student's t-test (two-sided): N.S = non-significant, *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "YY1: 
YY1: 22632"
  },
  {
    "caption": "H Coimmunoprecipitation and immunoblot analyses of extracts of 293T cells transfected with various combinations of plasmids encoding FLAG-tagged WTAP, and HA-tagged K48-linked, K63-linked or wild-type ubiquitin and treated with DMSO or PR171 (10 μM).",
    "ncbi_link": "HA: "
  },
  {
    "caption": "C qRT-PCR analyses to detect the mRNA abundances of IFNB1, RANTES, DDX58, and ISG15 in WT and WTAP-/- 293T cells followed by treatments with intracellular poly(I:C), poly(dA:dT), or VSV-eGFP.",
    "ncbi_link": "eGFP: 
RANTES: 6352
DDX58: 23586
IFNB1: 3456
ISG15: 9636
WTAP: 9589"
  },
  {
    "caption": "I, J Immunoblot analyses to detect the protein expression of ISGs in shCtrl and shWTAP A549 cells that were stimulated with poly(I:C)-LMW (I) or poly(dA:dT) (J) at different time points with the indicated antibodies.",
    "ncbi_link": "WTAP: 9589"
  },
  {
    "caption": "A, B Immunoblot analyses of total and phosphorylated (p-) TBK1 and IRF3 in A549 cells transfected with Ctrl or WTAP-specific siRNA, followed by stimulation with poly (I:C) (A) or poly (dA:dT) (B) at different time points.",
    "ncbi_link": "WTAP: 9589"
  },
  {
    "caption": "E, F Immunoblot analyses of total and phosphorylated (p-) STAT1 in shCtrl and shWTAP A549 cells, followed by stimulation with IFN-α (E) or -β (F) at different time points.",
    "ncbi_link": "WTAP: "
  },
  {
    "caption": "A, B Immunoblot analyses to detect the protein expression of critical adaptors in the IFN-I and Jak-STAT signaling pathway in A549 cells after transfection with Ctrl or WTAP-specific siRNAs for 48 hrs.",
    "ncbi_link": "WTAP: 9589"
  },
  {
    "caption": "F, G Abundance of IRF3 (F) and IFNAR1 (G) transcripts (detection site-1 and -2) among mRNA immunoprecipitated with anti-m6A antibody from shCtrl and shWTAP A549 cells. n = 3 independent biological replicates, and error bars represent standard deviations.",
    "ncbi_link": "IFNAR1: 3454
IRF3: 3661
WTAP: 9589"
  },
  {
    "caption": "(H) Representative  Iba1+ immunohistochemistry  in the choroid plexus of SPF, GF,  ABX-treated, ASF, recolonized ASF, sDMDMm2, TLR2,3,4,7,9-deficient, SCFA-treated GF mice or FFAR2-deficient  mice. Scale bar = 50 µm. (I-O) Quantification of stromal CPMΦ. Each symbol represents one mouse. Three to four sections per  mouse  were examined. Means ± s.e.m. are indicated. Significant differences were evaluated by unpaired t-test or one-way ANOVA followed by Tukey's post-hoc comparison test and marked with asterisks (*P < 0.05, **P < 0.01, ***P < 0.001). Data are representative of at least two independent experiments. ",
    "ncbi_link": "FFAR2: 233079
TLR2: 24088"
  },
  {
    "caption": "(H) Representative  Iba1+ immunohistochemistry in the perivascular space of SPF,  GF, ABX-treated, ASF, recolonized ASF, sDMDMm2, TLR2,3,4,7,9-deficient, SCFA-treated GF mice or FFAR2-deficient mice. Arrows indicate Iba1+ perivascular macrophages. Scale bar = 50 µm. (I-O) Quantification thereof. Each symbol represents one  mouse. Three to four sections per mouse were examined. Means ± s.e.m. are indicated. No significant differences were determined by unpaired t-test or one-way ANOVA followed by Tukey's post-hoc comparison test. Data are representative of at least two independent experiments. ",
    "ncbi_link": "FFAR2: 233079
TLR2: 24088"
  },
  {
    "caption": "(H) Representative Iba1+ immunohistochemistry in the leptomeninges of SPF, GF, ABX-treated, ASF, recolonized ASF, sDMDMm2, TLR2,3,4,7,9-deficient, SCFA-treated GF mice or FFAR2-deficient mice. Arrows indicate Iba1+ meningeal macrophages. Scale bar = 50 μm. (I-O) Quantification thereof. Each symbol represents one  mouse. Three to four sections per mouse were examined. Means ± s.e.m. are indicated. No significant differences were determined by unpaired t-test or one-way ANOVA followed by Tukey's post-hoc comparison test. Data are representative of at least two independent experiments. ",
    "ncbi_link": "FFAR2: 233079
TLR2: 24088"
  },
  {
    "caption": " . A representative example of a 7 days (7d) old adult female posterior midgut at low (A) and high magnification (B, Region 4-Region 5) showing the initiator caspase reporter DBS-S-QF (Red, immunostaining anti-HA). Flies were reared under experimental regime that protects the intestinal epithelial integrity (intestine reared in Oxford Medium and flies transferred every two days into vials with fresh food, see Figure EV1) at 25 Co. The image on the left was acquired at low magnification with the 10x objective, while the right panel was acquired using the 40x. The left and right images in all examples correspond to independent intestines of the same genotype and treatment. Genotype: y1 w1118 UAS-mCD8::GFP.L QUAS-mtdTomato-3xHA Act-DBS-S-QF (BL83131) ",
    "ncbi_link": "DBS-S-QF: 
GFP: 
HA: 
tdTomato: 
w1118: 
Act: 31521
CD8: 12525"
  },
  {
    "caption": "B. A representative example of a 7 d intestine reared at 29 Co in experimental conditions that protect the epithelial integrity and labelled with ReDDM cell-lineage tool. esg (green cytoplasmic signal) labels intestinal progenitor cells, whilst Histone-RFP (red nuclear signal) acts as a semi-permanent marker that allows the visualization of differentiated cells. Note the extensive overlap between the two markers and the absence of differentiated cells only showing the Histone-RFP labelling, as an indication of negligible epithelial turnover. The image on the left was acquired at low magnification with the 10x objective, while the right panel was acquired using the 40x. White dotted line outlines the gut using DAPI staining (not shown) as a reference. Genotype: w1118; esg-Gal4 UAS-CD8-GFP (Irene Miguel Aliaga)/ Cyo; UAS-Histone-RFP (BL7019) TubG80ts (BL7019 C. Quantification of intestinal cell subpopulations labelled with ReDDM system at high magnification (GFP and Histone-RFP) and different time points post ReDDM activation (3- and 7-days) in experimental conditions that protect the epithelial integrity; note that none of the cell populations in the gut (GFP (n.s. no significant , P = 0.5267) or Histone-RFP (n.s. , P =0.2752) significantly increase in number overtime (Quantifications were made using N ≥ 2 biological replicates, total number of guts analysed at 3 days n =34 and at 7 days n=45; Mann-Whitney, C). Error bars represent Standard Error of the Mean. Genotype: w1118; esg-Gal4 UAS-CD8-GFP (Irene Miguel Aliaga)/ Cyo; UAS-Histone-RFP (BL7019) TubG80ts (BL7019)",
    "ncbi_link": "Gal4: 
GFP: 
TubG80ts: 
w1118: 
CD8: 5740521"
  },
  {
    "caption": " D. A representative example of an adult female posterior midgut at low (A) and high magnification (B, Region 4-Region 5) showing the initiator caspase reporter DBS-S-QF (Red, immunostaining anti-HA) after 16 hours of paraquat treatment in Oxford food at 25 Co; note the expansion of the labelling with DBS-S-QF to large intestinal cells (ECs) (compare D with A). The image on the left was acquired at low magnification with the 10x objective, while the right panel was acquired using the 40x. White dotted line outlines the gut using DAPI staining as a reference. Genotype: y1 w1118 UAS-mCD8::GFP.L QUAS-mtdTomato-3xHA Act-DBS-S-QF (BL83131) ",
    "ncbi_link": "DBS-S-QF: 
GFP: 
HA: 
tdTomato: 
w1118: 
Act: 31521
CD8: 12525"
  },
  {
    "caption": " E. ReDDM lineage-tracing in an adult intestine reared in Oxford Medium and paraquat (20 mM) during 16 hours at 29 Co; note the abundance of Histone-RFP cells without GFP signal, as an indication of epithelial damage and subsequent differentiation of progenitor cells. The image on the left was acquired at low magnification with the 10x objective, while the right panel was acquired using the 40x. Genotype: w1118; esg-Gal4 UAS-CD8-GFP (Irene Miguel Aliaga)/ Cyo; UAS-Histone-RFP (BL7019) TubG80ts (BL7019) F. Quantification of ReDDM labelling at high magnification after paraquat treatment; note the statistically significant increase (**; P = 0.0099) of Histone-RFP expressing cells without GFP signal (Quantifications were made using N ≥ 2 biological replicates; Unpaired two-tailed t test, 3d n = 9, 7d n =7). Error bars represent Standard Error of the Mean. Genotype: w1118; esg-Gal4 UAS-CD8-GFP (Irene Miguel Aliaga)/ Cyo; UAS-Histone-RFP (BL7019) TubG80ts (BL7019) ",
    "ncbi_link": "Gal4: 
GFP: 
TubG80ts: 
w1118: 
CD8: 5740521"
  },
  {
    "caption": " H. Representative example of an intestine 7d old expressing two copies of the effector caspase inhibitor P35 under the regulation of esg-gal4 (green immunostaining with antibody against P35) at 29 Co. Genotype: w1118; esg-Gal4 UAS-CD8-GFP / UAS-P35 (BL5072); UAS-P35 (BL5073)/+ I. ReDDM lineage-tracing system in a Drosophila intestine expressing two copies of the effector caspase inhibitor P35 under the regulation of esg-Gal4 and experimental conditions that protect the epithelial integrity at 29 Co. Genotype: w1118; esg-Gal4 UAS-CD8-GFP/ UAS-P35 (BL5072); UAS-Histone-RFP TubG80ts / UAS-P35 (BL5073) J. ReDDM quantification corresponding to the intestines described in (I); no significant increase in either esg (n.s. , P = 0.1352) or Histone-RFP (n.s. , P = 0.9801) cell number is observed (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed t test, 3d n = 12, 7d n = 11). Error bars represent Standard Error of the Mean. DAPI (blue) labels the nuclei in panels A, D and H. Genotype: w1118; esg-Gal4 UAS-CD8-GFP/ UAS-P35 (BL5072); UAS-Histone-RFP TubG80ts / UAS-P35 (BL5073) ",
    "ncbi_link": "Gal4: 
gal4: 
GFP: 
TubG80ts: 
w1118: 
CD8: 5740521"
  },
  {
    "caption": "A. ReDDM activation in Dronc heterozygous (+/-) intestine 7 days after temperature shift at 29 Co; esg expression (green) labels the intestinal progenitor cells, Histone-RFP (red) is a semi-permanent marker retained in differentiated cells and Pdm-1 (grey) labels differentiated ECs. The red arrows indicates the enlarged areas depicted in the insets in the entire figure. DAPI labels the DNA In the entire Figure (blue). All of the experiments in the entire figure have been made under experimental conditions that protect the epithelial integrity (intestine reared in Oxford Medium and flies transferred every two days into vials with fresh food).",
    "ncbi_link": "Dronc: 39173"
  },
  {
    "caption": "B. ReDDM activation in a Drosophila intestine in which all of the progenitor cells are fully mutant for Dronc (see full genotype in methods); note the increased cell size of esg-expressing cells (GFP+, green), the co-expression of Histone-RFP (red) and the EC marker Pdm-1 (gray), and the coexpression of Pdm-1 and GFP in enlarged cells (compare panels and detailed insets from A with B). The image is a representative example of a Drosophila adult gut 7 days after temperature shift at 29 Co. Genotype: w1118; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry",
    "ncbi_link": "w1118: 
APEX: 
Cherry: 
Gal4: 
GFP: 
HA: 
TubG80ts: 
Dronc: 39173
CD8: 5740521"
  },
  {
    "caption": "C. Relative number of esg-expressing cells normalised to DAPI; notice that the relative percentage of esg-labelled cells is significantly higher in Dronc fully mutant conditions (-/-) at 3 days (***; P = 0.0007) and 7d (****; p <0.0001) post temperature shift at 29 Co (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed t-test, +/- n=32, -/- n=25).",
    "ncbi_link": "Dronc: 39173"
  },
  {
    "caption": " D. Average cell size of esg-expressing cells (μm²); note the increased cell size of Dronc fully mutant progenitor cells (-/-) at 3d (**; P = 0.0014) and 7d (***, P = 0.0007) post temperature shift at 29 Co (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed parametric t-test, 3d +/- n = 19, 3d -/- n = 28, 7d +/- n = 29, 7d -/- n = 28). ",
    "ncbi_link": "Dronc: 39173"
  },
  {
    "caption": "E. Relative number of esg-negative cells expressing Histone-RFP normalised to DAPI; notice that the number of Histone-RFP cells without esg expression is significantly higher in Dronc fully mutant (-/-) conditions at 7d (*; P = 0.0046) (Quantifications were made using N biological replicates ≥ 2; Mann-Whitney test, +/- n = 24, -/- n = 20.",
    "ncbi_link": "Dronc: 39173"
  },
  {
    "caption": " . A 7d intestine Dronc heterozygous (+/-) intestine in which intestinal stem cells express GFP under the regulation of Dl-Gal4. All of the experiments described in the figure were performed in Oxford medium following an experimental regime that protects the epithelial integrity (flies transferred every two days into vials with fresh food). DAPI (blue) labels the DNA in the entire Figure. Genotype: w1118; ;delta-Gal4 UAS-GFP TubG80ts UAS-Histone-RFP DroncKO/+ (recombinant chromosome made for this study; the parental line delta-Gal4 UAS-GFP TubG80ts UAS-Histone-RFP was obtained from Maria Dominguez) B. A 7d intestine in which the Intestinal Stem Cells have become Dronc homozygous mutant (-/-) upon expressing UAS-Flp under the regulation of Dl-Gal4. Dl-expressing cells are labelled with UASGFP (green); there are no morphological differences between A and B. Genotype: w1118; ;delta-Gal4 UAS-GFP TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry C. Relative number of GFP+ Delta-expressing cells normalised to DAPI; there is no significant increase in intestinal stem cell number between heterozygous and homozygous Dronc mutant conditions (ns; P = 0.9231) (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed t test, +/- n = 22, -/- n = 13). Error bars represent Standard Deviation of the Mean. Genotypes: +/- :w1118; ;delta-Gal4 UAS-GFP TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry -/- : w1118; ;delta-Gal4 UAS-GFP TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry D. Average Delta cell size (μm²); notice that the cell size does not change between heterozygous and homozygous Dronc mutant ISCs (ns; P = 0.9694) (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed t test, +/- n = 42, -/- n = 21). Error bars represent Standard Deviation of the mean. Genotypes:",
    "ncbi_link": "Flippase: 
Flp: 
APEX: 
Cherry: 
Gal4: 
GFP: 
HA: 
RFP: 
TubG80ts: 
w1118: 
Dronc: 39173"
  },
  {
    "caption": ". A 7d intestine Dronc heterozygous (+/-) intestine in which intestinal stem cells express GFP under the regulation of Su(H)-Gal4. Genotype: w1118; Su(H)-Gal4 UAS-GFP; TubG80ts UAS-Histone-RFP DroncKO/+ A 7d intestine in which the Enteroblasts have become Dronc homozygous mutant (-/-) upon expressing UAS-Flp under the regulation of Su(H)-Gal4. Su(H)-Gal4-expressing cells are labelled with UASGFP (green) and UAS-Histone-RFP; note the increase in cell size when compared to E and the absence of Histone-RFP cells without GFP signal. Genotype: w1118; Su(H)-Gal4 UAS-GFP; TubG80ts UAS-Histone-RFP DroncKO/ UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry Relative number of Su(H)-Gal4-expressing cells normalised to DAPI; there is no significant increase in intestinal stem cell number between heterozygous and homozygous Dronc mutant conditions (n.s. ; P = 0.5099) (Quantifications were made using N ≥ 2 biological replicates; Mann-Whitney test, +/- n = 30, -/- n = 29). Error bars represent Standard Deviation of the mean. Genotypes: +/- : w1118; Su(H)-Gal4 UAS-GFP; TubG80ts UAS-Histone-RFP DroncKO/+ -/- : w1118; Su(H)-Gal4 UAS-GFP; TubG80ts UAS-Histone-RFP DroncKO/ UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry H. Average Su(H) cell size (μm²), there is a significant increase in Su(H) Dronc null cells (-/-) when compared to the heterozygous control condition (**; P = 0.0064) (Quantifications were made using N ≥ 2 biological replicates; Mann-Whitney test, +/- n = 49, -/- n = 33). Error bars represent Standard Deviation of the mean. Genotypes: ",
    "ncbi_link": "Flippase: 
w1118: 
APEX: 
Cherry: 
Flp: 
Gal4: 
GFP: 
HA: 
TubG80: 
TubG80t: 
Dronc: 39173"
  },
  {
    "caption": "A. Representative ReDDM labeling of a Drosophila Dronc heterozygous (+/-) intestine overexpressing an RNAi against Notch for 3 days; note the lack of fully differentiated Histone-RFP cells as EC (red) without esg expression (green, GFP). DAPI staining labels cell nuclei in panels All of the experiments described in the figure were performed in Oxford medium following an experimental regime that protects the epithelial integrity. Genotype: w1118 UAS-Notch-RNAi (Joaquin Navascués); esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / + B. Representative ReDDM labelling of a Drosophila Dronc mutant homozygous (-/-) intestine overexpressing an RNAi against Notch for 3 post temperature shift at 29 oC; note the lack of differentiated Histone-RFP cells as EC (red) without esg expression (green, GFP), as well as the increase of GFP-positive cells (compare A to B). Genotype: w1118 UAS-Notch-RNAi (Joaquin Navascués); esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry C. Quantification of the number of Histone-RFP cells normalised to DAPI (proxy of progenitor cell proliferation obtained from the experiments shown in A and B panels); note the statically significant increase in Histone-RFP positive cells in Dronc homozygous mutant intestines compared to controls (**; P =0.0080) (Quantifications were made using N ≥ 2 biological replicates; unpaired two-tailed t test, +/- n = 8, -/- n = 15). Error bars represent Standard Deviation of the mean. Genotypes: +/-: w1118 UAS-Notch-RNAi; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / + -/-: w1118 UAS-Notch-RNAi (Joaquin Navascués); esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry ",
    "ncbi_link": "Cherry: 
Flippase: 
TubG80ts: 
w1118: 
APEX: 
GFP: 
HA: 
Dronc: 39173
Notch: 31293
CD8: 5740521"
  },
  {
    "caption": " D. Drosophila Dronc heterozygous intestine overexpressing the Notch intracellular domain for 7 days post temperature shift at 29 oC; intestinal esg-positive progenitor cells (green (GFP) and red (Histone-RFP). Genotype: w1118; esg-Gal4 UAS-CD8-GFP / UAS-Notchintra (Joaquin Navascués); TubG80ts UAS-Histone-RFP DroncKO / + E. Drosophila Dronc homozygous intestine overexpressing the Notch intracellular domain for 7d post temperature shift at 29 oC; notice that the Dronc deficiency accelerates the elimination of intestinal progenitor cells induced by Notch overactivation (compare D and E). The white arrows indicate the position of insets 500μm from the posterior region. Note the complete loss of esg labelled cells in this region. Genotype: w1118; esg-Gal4 UAS-CD8-GFP / UAS-Notchintra; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry F. Relative number of esg-positive cells to DAPI in either heterozygous or homozygous Dronc mutant esg cells overexpressing Notch-Intra; note the significant reduction of esg-expressing cells (****; P < 0.0001) (Quantifications were made using N ≥ 2 biological replicates; Mann-Whitney test, +/- n = 17, -/- n = 17). Error bars represent Standard Deviation of the mean. Genotypes: +/-: w1118; esg-Gal4 UAS-CD8-GFP / UAS-Notchintra ; TubG80ts UAS-Histone-RFP DroncKO / + -/-: w1118; esg-Gal4 UAS-CD8 -GFP / UAS-Notchintra; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry",
    "ncbi_link": "Flippase: 
TubG80ts: 
w1118: 
APEX: 
Cherry: 
GFP: 
HA: 
Dronc: 39173
Notch: 31293
CD8: 5740521"
  },
  {
    "caption": "G. Representative image of a Drosophila Dronc heterozygous intestines 7 days after transfer to 29 oC. esg expression in green (GFP) labels all intestinal progenitors cells, whilst Su(H)-lacZ (red) distinguishes a subpopulation of EBs within the esg-expressing cells. Genotype: w1118, Su(H)GBE-LacZ; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / +",
    "ncbi_link": "w1118: 
GFP: 
TubG80ts: 
Dronc: 39173
CD8: 5740521"
  },
  {
    "caption": "H. Representative image of a Drosophila Dronc KO intestine 7 days after transfer to 29 oC. Note, the transcription of Su(H) in large cells GFP (-), suggestive of an aberrant upregulation of Notch-signalling within fully differentiated ECs. Genotype: w1118, Su(H)GBE-LacZ; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry",
    "ncbi_link": "Flippase: 
w1118: 
APEX: 
Cherry: 
GFP: 
HA: 
TubG80ts: 
Dronc: 39173
CD8: 5740521"
  },
  {
    "caption": "I. Representative image of a 7d Drosophila Dronc heterozygous intestines following a 16hr treatment with paraquat. Note the absence of large Su(H) positive, GFP (-) cells compared to (H). The white arrows indicate the enlarged area depicted in the insets. Genotypes: +/-: w1118, Su(H)GBE-LacZ; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / + -/-: w1118, Su(H)GBE-LacZ ; esg-Gal4 UAS-CD8-GFP / + ; TubG80ts UAS-Histone-RFP DroncKO / UAS-Flippase (BL8209) FRT Dronc-GFP-APEX FRT suntag-HA-Cherry",
    "ncbi_link": "Flippase: 
w1118: 
APEX: 
Cherry: 
GFP: 
HA: 
TubG80ts: 
Dronc: 39173
CD8: 5740521"
  },
  {
    "caption": "B. Growth comparisons of selected kinases with the kinase‑dead mutant match. 24h growth curves (OD595) from liquid culture of yeast strains (W303) expressing human kinase in the presence or absence of 3.2% (v/v) DMSO. Upper panel: BUB1: BUB1 wild type, BUB1-KD: BUB1(K821M); upper middle panel: NEK6: NEK6 wild type, NEK6-KD: NEK6(K74M&K75M); lower middle panel: PKCα-ac: PKCα(A25E), PKCα-KD: PKCα(K368R); lower panel: Control with empty plasmid. Error bars represent SD from three biological replicates.",
    "ncbi_link": "BUB1: 699
NEK6: 10783
PKCα: 5578"
  },
  {
    "caption": "C. Y2H interaction experiment with human AAR2 (FL) as bait and PRP8 (aa1755-2335) as prey. Growth on selective media is abolished when AAR2 carries a S284E phospho-mimicry amino acid substitution. Mutation of second candidate phospho-site, AAR2(T356), does not influence the AAR2-PRP8 protein interaction.",
    "ncbi_link": "AAR2: 25980"
  },
  {
    "caption": "D. Interaction of AAR2 and PRP8 in human cells. HA‑tagged PRP8 (aa1755-2335) was co-expressed in HEK293 cells with either wildtype AAR2, AAR2(S284A) or AAR2(S284E) mutant versions. Immunoprecipitation of PRP8 led to a co-precipitation of wild typeAAR2 and phospho-null AAR2(S284A). In contrast, the phospho-mimicry AAR2(S284E) version did not bind PRP8.",
    "ncbi_link": "AAR2: 25980"
  },
  {
    "caption": "E. Results of the phospho-Y2H screen to identify kinases modulating the interaction of AAR2 and PRP8. Growth on selective media (SD5), of strains carrying AAR2 bait and PRP8 prey plasmids is reduced through co-expression of either SGK2 or CK2α1(CSNK2A1). Growth reduction is visible in a 1:10 dilution series on selective agar (SD5) in comparison to the control media (SD3). Ctrl: non-related kinases.",
    "ncbi_link": "CK2α1: 1457
CSNK2A1: 1457
SGK2: 10110"
  },
  {
    "caption": "F. Interaction of AAR2 and PRP8 in human cells in the presences of SGK and CK2α1 kinases. Experiment as in D. Co-expression of wild type SGK2 and CK2α1 reduces the amount of AAR2 co-immunoprecipitated with RPR8.",
    "ncbi_link": "AAR2: 25980
CK2α1: 1457
SGK: 10110
SGK2: 10110"
  },
  {
    "caption": "B. Results of the phospho-Y2H screen to identify kinases modulating the interaction of the ERα with 14‑3‑3β. The interaction of ERα (prey) with 14‑3‑3β (bait) is promoted by the co-expression of wildtype kinases of PAK5, CDK17, BUB1 and NEK6, visible by the yeast growth on selective media in comparison to the control (three biological replicas are shown). The coexpression of the kinase‑dead mutants of PAK5 and CDK17 also promoted the interaction of ERα and 14‑3‑3β. In contrast the kinase‑dead mutant versions of BUB1(K821M) and NEK6(K74M&K75M) did not promote the Y2H interaction.",
    "ncbi_link": "BUB1: 699
CDK17: 5128
NEK6: 10783
PAK5: 57144"
  },
  {
    "caption": "D. Interaction of ERα and 14‑3‑3β in a GST pull-down assay. GST‑tagged 14‑3‑3β was expressed in E. coli and immobilized on beads. PA‑tagged ERα was co-expressed with either wildtype PAK5 or NEK6, the kinase‑dead (KD) version or without a kinase in HEK293 cells. Immobilized 14‑3‑3β was used to pull PA‑tagged ERα from the HEK lysates. Co-precipitation of ERα was successful in the presence of wild kinases, but not in their absence or with kinase‑dead mutant versions.",
    "ncbi_link": "NEK6: 10783
PAK5: 57144"
  },
  {
    "caption": "E. Effect of NEK6 co-expression on ERα gene activation. Relative luciferase activity of ERα in the presence and absence of 1 nM E2 (17β-estradiol) was measured. A dose‑dependent reduction (ng plasmid transfected) in E2-Erα‑dependent luciferase expression was observed in HEK293T, MCF-7 and US-OS cancer cell lines. This effect was not observed with the NEK6(K74M&K75M) kinase‑dead version. Graphs represent ≥ 5 biological replicates, each derived from averaging 6 technical replicates. Error bars indicate SD across the biological replicates.",
    "ncbi_link": "luciferase: 
ERα: 2099
Erα: 2099
NEK6: 10783"
  },
  {
    "caption": "B-J: Representative immunofluorescences of the cell types composing the WT and Mecp2 null cultures differentiated from NPCs. Antibodies against Tuj1, Gfap and Olig2 were used to recognize neurons, astrocytes and oligodendrocytes. In D, G and J the percentage of cells positive (mean ± SEM) for each marker was counted over the total of DAPI positive cells (100%). No difference between genotypes was highlighted (Two-way ANOVA); the variation through time resulted significant for the levels of Tuj1 and Gfap (Two-way ANOVA: F(1,16)=9.542, p-value<0.05 and F(1,10)=68.95, p-value<0.0001 respectively). Sample size: n ≥3 wells obtained from two independent preparations; for each well 10 random fields were acquired. Scale bars: 30 µm.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "P: Scatter plots describing the transcriptional levels of selected differentially expressed genes in WT and Mecp2 null cultures differentiated from NPCs and analysed at DIV3 and DIV14. For each gene Two-way ANOVA and Šidák multiple comparison test were used to assess difference between genotypes at the two selected time points (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Values are represented as mean ± SEM. Sample size: ≥5 samples obtained from two independent preparations.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Bar graphs represent the expression values (mean ± SEM) of 27 genes, selected for their downregulation in null samples at DIV 14 (p-value <0,07; see Appendix Figure S2), after CX546 administration in the two different time windows (early in G and late in H). One-way ANOVA followed by Dunnett's multiple comparison test was used to compare the expression of each gene between Mecp2 null early and late treated samples and their corresponding untreated controls (set to 1, red dotted line). *: p-value<0.05; **: p-value<0.01, ***: p-value<0.001, ****: p-value<0.0001. Sample size: n≥8 wells deriving from two independent preparations. Each point is representative of a single well.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "I,J: In I One-way ANOVA was used to compare the expression of 9 neuronal genes between Mecp2 null primary neurons (set to 100), null neurons treated with CX546 from DIV1 to DIV4 and null neurons treated with CX546 and Nifedipine from DIV1 to DIV4. * refers to differences between Mecp2 null untreated neurons and Mecp2 null neurons treated with CX546 (*: p-value<0.05; **: p-value<0.01; ***: p-value<0.001); # refers to differences between Mecp2 null neurons treated with CX546 and null neurons treated with both CX546 and Nifedipine (#: p-value<0.05; ##: p-value<0.01). Panel J shows the ratio between the expression level of Kcc2 and Nkcc1 (expressed as 2-∆ct). Box plot shows the median (central band), the lower and upper quartiles (boxes) and the max and min values (whiskers) from at least 3 wells obtained from four different embryos. One-way ANOVA was used to compare the effects of the different treatments on null neurons compared to the untreated ones. **: p-value<0.01. Sample size: n≥3 wells from four different embryos.",
    "ncbi_link": "Mecp2: 17257
Nkcc1: 20496
Kcc2: 57138"
  },
  {
    "caption": "B: Kaplan Mayer test shows an improved lifespan of Mecp2 null CX546 treated animals compared to Mecp2 null control animals. Sample size: wt=11, ko=16, ko treated with CX546=11. Gehan-Breslow-Wilcoxon test was used to compare the two groups. **: p-value<0.01.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "(A, B) qRT-PCR analysis of IL6 expression upon indicated stimulations in presence or absence of NOD1 (A) or NOD2 (B). HeLa inducible NOD1 cells (A) or NOD2 cells (B) were induced in absence or presence of doxycycline overnight and afterwards stimulated with various stimuli for 4 h.",
    "ncbi_link": "IL6: 3569
NOD1: 10392
NOD2: 64127"
  },
  {
    "caption": "(C) qRT-PCR analysis of Cxcl2 expression upon indicated stimulations in WT, Nod1/2 KO and Rip2 KO bone marrow derived macrophages (BMDMs).",
    "ncbi_link": "Cxcl2: 2920
Nod1: 10392
Rip2: 8767"
  },
  {
    "caption": "(H) qRT-PCR analysis of Cxcl2 expression in WT, Sphk1 KO or Sphk2 KO BMDMs upon indicated stimulations for 4 h.",
    "ncbi_link": "Cxcl2: 20310
Sphk1: 20698
Sphk2: 56632"
  },
  {
    "caption": "(D) Western blot analysis of MAPKs and NF-κB activation upon S1P stimulation. HeLa NOD1 or NOD2 cells were treated with cytosolic S1P (20 µM), iE-DAP (20 µM) or MDP (20 µM) for indicated times.",
    "ncbi_link": "NOD1: 10392
NOD2: 64127"
  },
  {
    "caption": "Multiplex analysis of CXCL2 (I), CCL5 (J) and IL16 (K) production in supernatants of WT, Nod1/2 and Rip2 KO BMDMs upon S1P (10 µM) or MDP (10 µM) stimulations together with digitonin (2.5 µg/ml) for 20 h.",
    "ncbi_link": "Nod1: 10392
Rip2: 8767"
  },
  {
    "caption": "(A, B) Immunoprecipitation with various lipid-coated beads using HeLa NOD1-GFP (A) and NOD2-GFP cells (B). Cell lysates of HeLa NOD1 or HeLa NOD2 cells were incubated with lipid-coated beads at room temperature for 2 h.",
    "ncbi_link": "GFP: 
NOD1: 10392
NOD2: 64127"
  },
  {
    "caption": "(F) ELISA analysis of IL8 in supernatants of HEK293T NOD1/2 KO cells transfected with indicated NOD1 or NOD2 mutants. After 24 h transfection, cells were stimulated with S1P (20 µM), iE-DAP (20 µM) or MDP (20 µM) together with digitonin for 20 h.",
    "ncbi_link": "NOD1: 10392
NOD2: 64127"
  },
  {
    "caption": "E, Kaplan-Meier  plot depicting metastasis   onset after tumor removal in mice  injected orthotopically with SUM159PT  WT (n = 10), KO (KOd: n = 5; KOs: n = 5) or KO-NNMT  (KOd-NNMT: n= 5; KOs-NNMT: n= 5) cells. *P < 0.05; Log-rank test.",
    "ncbi_link": "NNMT: 4837"
  },
  {
    "caption": "F, Bar graph quantification (left panel) and representative bioluminescence images (right panel) of metastases  at day 75 after cancer cell injection of  MDA-MB-231 KO1- RFP  or KO1- NNMT  cells and post-primary tumor removal. n = 7 to 10 animals per group. *P < 0.05; Mann-Whitney U-test. All data are means ± SD. G, Bar graph quantification (left panel) and representative bioluminescence images (right panel) of metastases  at day 34 after injection of MDA-MB-231 KO1- RFP  or KO1- NNMT  cells into the tail veins of mice. n = 10 animals per group. ***P < 0.001; Mann-Whitney U-test. All data are means ± SD.",
    "ncbi_link": "RFP: 
NNMT: 4837"
  },
  {
    "caption": "D, Dot plots depicting the overlap of H3K9me3 ChIP-sequencing  and mRNA-sequencing data. In the y axis: differential H3K9me3 enrichment at the gene promoter in NNMT  KO compared to WT cells. In the x axis: differential mRNA expression  of NNMT  KO compared to WT cells. n = 3 experimental replicates. Cut-off: adjusted P < 0.05. Bold dots highlight collagen genes and PRDM5.",
    "ncbi_link": "NNMT: 4837
PRDM5: 11107"
  },
  {
    "caption": "F, Bar graph representing average PRDM5  mRNA expression  in  SUM159PT KOs, KOd, and WT cells. n = 3 experimental replicates with 2 technical replicates each. ****P < 0.0001; Mann-Whitney U-test. All data are means ± SD.",
    "ncbi_link": "PRDM5: 11107"
  },
  {
    "caption": "G, H, Bar graphs representing average collagen gene mRNA expression  upon overexpression (OE) of PRDM5  in SUM159PT  KOd and KOs cells. n = 3 to 5 experimental replicates with 2 technical replicates each. *P < 0.05, **P < 0.01, n.s., not significant; Kruskal-Wallis test. All data are means ± SD.",
    "ncbi_link": "PRDM5: 11107"
  },
  {
    "caption": "E, Bar graphs representing average PRDM5  and collagen gene mRNA expression  upon 5- aza  treatment in SUM159PT  WT, Kos, and KOd cells. n = 3 experimental replicates with 2 technical replicates each. *P < 0.05, n.s., not significant; Kruskal-Wallis test. Data are means ± SEM.",
    "ncbi_link": "PRDM5: 11107"
  },
  {
    "caption": "A, Bar graph quantification (left panel) and representative bioluminescence images (right panel) of metastases  at day 27 after injection of  MDA-MB-231 cells into the  tail veins  of mice  bearing short hairpin sh NT (non-targeting), sh1 or sh2 targeting PRDM5. Mice  were fed with doxycycline  food to sustain shRNA expression during the whole experiment. n = 7 to 8 animals per group. **P < 0.01; One-way ANOVA. All data are means ± SD.",
    "ncbi_link": "PRDM5: 70779"
  },
  {
    "caption": "B, Box plots depicting bioluminescence quantification (left panel) and representative images (right panel) of metastases  at day 42 and day 62 after intravenous injection of  MDA-MB-231 KO1_RFP, KO1_NNMT1 and KO1_COL1A1 (COL1A1  over-expression) cells. n = 4 to 8 animals per group. **P < 0.01, ***P < 0.001; Day 42: One-way ANOVA, Day 62: Student t-test. Boxes define the upper and lower quartiles; central band indicate the median; whiskers define max to min values.",
    "ncbi_link": "RFP: 
COL1A1: 1277
NNMT1: 4837"
  },
  {
    "caption": "C Genetically recovered flies of Ir25a2 and Ir76b1 driven by their own GAL4 or Gr64f-GAL4 with the wild-type cDNA transgene. +/- indicate the presence or absence of the transgene, respectively, n = 10-15.",
    "ncbi_link": "GAL4: 855828
Gr64f: 117477
Ir25a: 33683
Ir76b: 40198"
  },
  {
    "caption": "D Genetically recovered flies of Gr5a, Gr61a, Gr64b, Gr64c, and Gr64e mutants driven by their own GAL4 or Gr64f-GAL4. +/- indicate the presence or absence of the transgene, respectively, n = 10-21.",
    "ncbi_link": "GAL4: 855828
Gr5a: 44873
Gr61a: 38098
Gr64b: 117480
Gr64c: 117479
Gr64e: 3771916
Gr64f: 117477"
  },
  {
    "caption": "D Behavioral rescue of Gr5a∆5, Gr61a1, Gr64bLEXA, Gr64cLEXA, and Gr64eLEXA deficits in the vitamin C attraction via the expression of the respective UAS transgenes under the control of their specific GAL4s or Gr64f-GAL4, n = 6-8.",
    "ncbi_link": "GAL4s: 855828
GAL4: 855828
Gr5a: 44873
Gr61a: 38098
Gr64b: 117480
Gr64c: 117479
Gr64e: 3771916
Gr64f: 117477"
  },
  {
    "caption": "Death rate plotted versus growth rate on a semi-log scale for experiments in 'osmo-balanced' medium. Colors indicate carbon limitation (C, 'blue', acetate and glycerol), anabolic limitation (A, 'green', 3µM IPTG), ribosome limitation (R, 'yellow', 4µM Chloramphenicol), rich medium (L, 'red', LB), LacZ overexpression (O, 'grey', 10ng/ml cTc), stationary phase (S, 'white') and the glucose reference condition ('black'), as defined in Fig. 1A. The data shows weak anti-correlation with growth rate; solid black line is an exponential fit to the data (R2 = 0.34). Dashed lines are the exponential fits to the CARLOS data in Fig. 1A.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "H NF2 and WWC2 interact with LATS1 as indicated by BioID labeling. HEK293A cells stably expressing BirA-NF2, WWC2, MOB1A, or SAV1 were labeled with biotin overnight, and endogenous kinases were immunoprecipitated and subjected to immunoblotting using Streptavidin-HRP. No biotinylation of MAP4K4 was detected.",
    "ncbi_link": "BirA: 948469
MOB1A: 55233
NF2: 4771
SAV1: 60485
WWC2: 80014"
  },
  {
    "caption": "B-D NF2 is required for the activation of LATS1/2 by RAP2A. WT and NF2 KO HEK293A cells were transfected with or without HA-RAP2A. Immunoprecipitated LATS1 (B), MAP4K4 (C) or MST1(D) was then subjected to in vitro kinase assays.",
    "ncbi_link": "HA: 
NF2: 4771
RAP2A: 5911"
  },
  {
    "caption": "E, F NF2 is required for the activation of LATS1/2 by MAP4K kinases. MST1/2 dKO or MST1/2;NF2 3KO cells were transfected with siRNAs against STRIP1/2. Immunoprecipitated MAP4K4 (E) or LATS1 (F) was then subjected to in vitro kinase assays.",
    "ncbi_link": "MST1: 4485
NF2: 4771
STRIP1: 85369"
  },
  {
    "caption": "B Concurrent deletion of Nf2 and Wwc1/2 at developmental stage driven by Alb-Cre results in liver dysfunction and perinatal death. Gross liver images, H&E, IHC, and IF images of 3-day-old livers from WT and Nf2;Wwc1/2 compound KO mice were shown. Scale bars: 1 cm (gross liver image), 50 μm (H&E and IHC), 20 μm (IF).",
    "ncbi_link": "Alb: 11657
Cre: 2777477
Nf2: 18016
Wwc1: 211652"
  },
  {
    "caption": "E, F Activities of Hippo pathway kinases in Nf2;Wwc1/2 deficient livers. LATS1, MST2, and MAP4K4 were immunoprecipitated from control or Nf2F/F;Wwc1F/F;Wwc2F/F (Ad-Cre) mouse livers (4 each), and kinase assays were performed (E) and quantified (F). Four biological replicates were shown in F, error bars indicate SEM.",
    "ncbi_link": "Ad: 104253
Cre: 2777477
Nf2: 18016
Wwc1: 211652
Wwc2: 52357"
  },
  {
    "caption": "Phenotypes of 1-week-old livers with HPO1 and/or HPO2 gene deletions. liver/body weight ratio (B) of WT, Nf2-/-, Sav1-/-, Wwc1-/-;Wwc2-/-, Mst1-/-;Mst2Δ/Δ and compound KO mice. Scale bar in A: 1cm. Each data point in B stands for one mouse, data shown are mean + SEM.",
    "ncbi_link": "Mst1: 15235
Nf2: 18016
Sav1: 64010
Mst2: 56274
Wwc1: 211652
Wwc2: 52357"
  },
  {
    "caption": "C HPO1 and HPO2 inactivation results in rapid iCCA. H&E and CK19 staining for Nf2-/- (8-month-old), Nf2-/-;Sav1-/- (1-week-old) and Nf2-/-;Wwc1-/-;Wwc2+/- (1-week-old) livers. Nf2-/- liver displayed bile duct hyperplasia at 8 months, while Nf2-/-;Sav1-/- and Nf2-/-;Wwc1-/-;Wwc2+/- livers at 1 week exhibited massive expansion of cholangiocytes with enlarged nuclei, irregular shape, and invasive behaviors. Nf2-/-;Sav1-/- also exhibited cholestasis, as indicated by asterisk. Scale bar: 20 μm (H&E and IHC).",
    "ncbi_link": "Nf2: 18016
Sav1: 64010
Wwc1: 211652
Wwc2: 52357"
  },
  {
    "caption": "A Measurement of urinary albumin/creatinine by ELISA (albumin-to-creatinine ratio: day 14: Phb2fl/fl 0.09 ± 0.03 mg/mg, n = 4, versus Phb2pko 0.37 ± 0.21 mg/mg, n = 4, P = 0.2350; day 21: Phb2fl/fl 0.65 ± 0.16 mg/mg, n = 4, versus Phb2pko 193.10 ± 26.81 mg/mg, n = 4, ***P = 0.003; day 28: Phb2fl/fl 0.57 ± 0.07 mg/mg, n = 4, versus Phb2pko 470.40 ± 131.30 mg/mg, n = 4, *P = 0.0117).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "B Appearance of Phb2fl/fl and Phb2pko mice at day 28.",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "C Analysis of body weight from postnatal day 14 until day 32 (P-values for Phb2fl/fl or Phb2het versus Phb2pko: *P = 0.0372 at day 27, *P = 0.0311 at day 28, *P = 0.0157 at day 29, **P = 0.008 at day 30, **P = 0.0013 at day 31, **P = 0.0035 at day 32, n = 3 for Phb2fl/fl and n = 4 for Phb2het and Phb2pko).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "D Measurement of serum creatinine levels of mice in their fifth week of life (Phb2fl/fl/het 14.74 ± 3.75 μmol/l versus Phb2pko 74.73 ± 2.20 μmol/l, n = 3 for both groups; ***P = 0.0002).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "E Measurement of serum urea levels of mice in their fifth week of life (Phb2fl/fl/het 44.00 ± 7.02 mg/dl versus Phb2pko 493.70 ± 45.34 mg/dl, n = 3 for both groups; ***P = 0.006).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "F Kaplan-Meier survival curve (n = 5 for Phb2fl/fl/het and n = 6 for Phb2pko).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "Phb2pko mice develop glomerulosclerosisA PAS staining of kidney sections (scale bar: 20 μm).B Immunohistochemistry for podocin on kidney sections (scale bar: 20 μm).C Analysis of podocyte foot processes in electron micrographs (scale bar: 0.7 μm). FP, podocyte foot processes; GBM, glomerular basement membrane; EC, endothelial cells.D Analysis of mitochondrial morphology in electron micrographs (arrows; scale bar: 0.3 μm).E High-power view of mitochondria in electron micrographs (scale bar: 0.1 μm).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "A PAS staining of tPod-Phb2pko and control mice 2.5 weeks after the end of tamoxifen treatment (scale bar: 20 μm).B Immunohistochemistry for podocin on kidney sections of tPod-Phb2pko and control mice 2.5 weeks after the end of tamoxifen treatment (scale bar: 20 μm).",
    "ncbi_link": "Pod: 170484
Phb2: 12034"
  },
  {
    "caption": "C Coomassie stain of urinary samples of tPod-Phb2pko and control mice.",
    "ncbi_link": "Pod: 170484
Phb2: 12034"
  },
  {
    "caption": "A Kaplan-Meier survival curve showed that an additional knockout of the insulin receptor (Insr) prolonged survival of Phb2pko mice (n = 7 for Phb2pko/Insrpko, n = 4 for Phb2pko/Insrhet, and n = 6 for Phb2pko).",
    "ncbi_link": "Insr: 16337
Phb2: 12034"
  },
  {
    "caption": "B Kaplan-Meier survival curve revealed that the survival time of Phb2pko mice is not changed by an additional Igf1r deficiency (n = 6 for Phb2pko/Igf1rpko, n = 4 for Phb2pko/Igf1rhet, and n = 6 for Phb2pko).",
    "ncbi_link": "Igf1r: 16001
Phb2: 12034"
  },
  {
    "caption": "C Statistical analysis comparing all genotypes with Phb2pko mice.",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "D Kaplan-Meier survival curve revealed prolonged survival of Phb2pko/Insrpko/Igf1rpko and Phb2pko/Insrpko/Igf1rhet mice (n = 19 for Phb2pko/Insrpko/Igf1rpko, n = 9 for Phb2pko/Insrhet/Igf1rpko, n = 11 for Phb2pko/Insrpko/Igf1rhet, n = 9 for Phb2pko/Insrhet/Igf1rhet, and n = 6 for Phb2pko).E Statistical analysis comparing all genotypes with Phb2pko mice.",
    "ncbi_link": "Igf1r: 16001
Insr: 16337
Phb2: 12034"
  },
  {
    "caption": "A Serum creatinine and urea levels in the fifth week of life (left graph: Phb2pko 74.73 ± 2.20 μmol/l versus Phb2pko/Insrpko/Igf1rpko 37.36 ± 8.83 μmol/l, n = 3 for Phb2pko and n = 4 for Phb2pko/Insrpko/Igf1rpko, *P = 0.0169; right graph: Phb2pko 493.70 ± 45.34 mg/dl versus Phb2pko/Insrpko/Igf1rpko 272.80 ± 49.29 mg/dl, n = 3 for Phb2pko and n = 4 for Phb2pko/Insrpko/Igf1rpko, *P = 0.0247).",
    "ncbi_link": "Igf1r: 16001
Insr: 16337
Phb2: 12034"
  },
  {
    "caption": "B Abundance of deleted Phb2 gene in isolated glomeruli of Phb2fl/fl, Phb2het, Phb2pko and Phb2pko/Insrpko/Igf1rpko mice compared to the floxed Phb2 gene (left graph; quantified by qPCR: n = 3 for all groups, P = 0.83 for Phb2pko/Insrpko/Igf1rpko versus Phb2pko) and compared to a reference gene (right graph; quantified by qPCR: n = 3 for all groups, P = 0.58 for Phb2pko/Insrpko/Igf1rpko versus Phb2pko).",
    "ncbi_link": "Igf1r: 16001
Insr: 16337
Phb2: 12034"
  },
  {
    "caption": "A Immunofluorescence staining of mPhb2 shRNA and control podocytes with a Tom20 antibody revealed a disturbed mitochondrial network in Phb2-deficient podocytes (scale bar: 10 μm).B Quantification of tubular and fragmented mitochondrial morphology mPhb2 shRNA versus control podocytes seen in (A) (mitochondrial network of n = 100 individual cells of mPhb2 shRNA podocytes and n = 108 individual cells of scrambled shRNA podocytes was assessed).C Morphometric image analysis revealed an increased ratio of mitochondrial count versus mitochondrial area in Phb2-deficient podocytes compared to control podocytes (n = 75 cell patches for scrambled shRNA, n = 58 cell patches for mPhb2 shRNA).D Morphometric image analysis showed a decrease in branch numbers in Phb2-deficient podocytes compared to control podocytes (n = 75 cell patches for scrambled shRNA, n = 58 cell patches for mPhb2 shRNA).E Morphometric image analysis detected a decrease in mitochondrial size in Phb2-deficient podocytes compared to control podocytes (n = 75 cell patches for scrambled shRNA, n = 58 cell patches for mPhb2 shRNA).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "F Measurements of mitochondrial respiration with complex II substrates (succinate and glycerol-3-phosphate) did not show significant differences between Phb2-deficient and control podocytes (n = 6).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "G Quantification of mtDNA as a measure for mitochondrial mass showed similar levels of mtDNA in Phb2-deficient podocytes compared to control podocytes (n = 3).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "H FACS analysis of MitoTracker- and MitoSOX-stained Phb2-deficient podocytes and control podocytes.I Quantification of mean fluorescence intensity of MitoTracker and MitoSOX by FACS analysis revealed the same mitochondrial mass and the same ROS levels in Phb2-deficient podocytes compared to control podocytes (n = 3, P = 0.7782 for MitoTracker, P = 0.1088 for MitoSOX).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "A Phb2-deficient mouse podocytes showed higher levels of phosphorylated S6 ribosomal protein than control podocytes, which could be blocked by treatment with rapamycin (n = 5, bars represent mean ± SEM, Student's t-test, **P = 0.0036). pS6RP, phosphorylated S6 ribosomal protein; S6RP, S6 ribosomal protein.",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "B Immunohistochemistry for phosphorylated S6 ribosomal protein (pS6RP) on kidney sections revealed increased levels of pS6RP in glomeruli of Phb2pko compared to Phb2fl/fl mice (arrows point to cells showing a signal for pS6RP; scale bar: 20 μm).",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "C Kaplan-Meier survival curve revealed that treatment of Phb2pko mice with rapamycin prolonged survival for several days compared to vehicle-treated Phb2pko mice (n = 11 for Phb2fl/fl + rapamycin, n = 15 for Phb2pko + vehicle, n = 16 for Phb2pko + rapamycin).D Statistical analysis comparing rapamycin-treated Phb2pko mice with vehicle-treated Phb2pko mice.",
    "ncbi_link": "Phb2: 12034"
  },
  {
    "caption": "WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the left rear footpad with 103 PFU of CHIKV. (E) Viral tissue burdens were analyzed at 1 day post inoculation (dpi) by FFA. Mean ± SEM.",
    "ncbi_link": "MARCO: 17167"
  },
  {
    "caption": "WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the left rear footpad with 103 PFU of ONNV (F) Tissues and serum were collected at 1 dpi and analyzed by plaque assay.",
    "ncbi_link": "MARCO: 17167"
  },
  {
    "caption": "WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the left rear footpad with 103 PFU of RRV (G). Tissues and serum were collected at 1 dpi and analyzed by plaque assay.",
    "ncbi_link": "MARCO: 17167"
  },
  {
    "caption": "(B) WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the left rear footpad with 108 particles of WT CHIKV or CHIKV E2 K200R. Viral genomes in the dLN and serum at 2 hpi were quantified by RT-qPCR. Mean ± SD. Data are pooled from two experiments, n=10. Two-way ANOVA with Bonferroni's multiple comparisons test; ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "E2: 
MARCO: 17167"
  },
  {
    "caption": "(C) WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the left rear footpad with 108 particles of RRV. Viral genomes in the dLN and serum were quantified by RT-qPCR. Mean ± SD. Data are pooled from two experiments, n=8-9. Mann-Whitney test; ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "MARCO: 17167"
  },
  {
    "caption": "WT or MARCO-/- C57BL/6 mice were inoculated s.c. in the rear feet with 5*104 PFU of CHIKV-E2-mCherry and the popliteal dLNs were collected at 2 hpi. (A) Frozen dLN sections were stained for Lyve-1+ LECs (white), MARCO (green), B220 (blue) and mCherry+ CHIKV particles (red). Scale bars: 200 μm. ",
    "ncbi_link": "MARCO: 17167"
  },
  {
    "caption": "B, C Kinetic change of mRNA expression  of Top1, Btbd1, Tdp1, and Srsf1  in microglia  following LPS/IFNγ  stimulation (n = 6, technical replicates). Data information: Data are presented as the mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001; Statistical analyses were performed using two-way ANOVA with Dunnett's Multiple Comparison test for (B and C),",
    "ncbi_link": "Btbd1: 83962
Srsf1: 110809
Tdp1: 104884
Top1: 21969"
  },
  {
    "caption": "O Microglia  were sorted from LPS  challenged mice  (i.p) after 4 h or naive mice, and the mRNA expression  of TOP1  was graphed (n = 5 or 6 biological samples). Data information: Data are presented as the mean ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001 Statistical analyses were performed using the student's unpaired two-tailed t-test.",
    "ncbi_link": "TOP1: 21969"
  },
  {
    "caption": "B. Fold repression of Renilla expression (compared to reporter plasmid transfection alone) versus the amount of transfected siRNA duplex, wild-type HsAGO2-siRNA complex, or HsAGO2+At-loop-siRNA complex. The 2-8 target (left panel) indicates miRNA-like targeting. The 2-19 target (right panel) indicates siRNA-like targeting. Dotted line indicates the normalized expression level of the positive control (no repression). Graphed data in B represent the individual and the ratio of mean values of n=3 independent biological trials, respectively. Error bars indicate s.e.m. ANOVA with Dunnett's posthoc test P values: ** = 0.0062, * = 0.0363. No data points were excluded from the analyses.",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "B. Prey specificity graph for BioID interactome of TRUB2 protein. Prey specificity was calculated as the relative enrichment of interaction of individual preys and TRUB2, compared to their interaction with 138 other baits (42 mitochondrial baits, 96 baits from other cellular compartments).",
    "ncbi_link": "TRUB2: 26995"
  },
  {
    "caption": "D, E. Pulse-labeling mitochondrial translation experiment of the 13 mitochondria-encoded polypeptides (seven subunits of complex I [ND], three subunits of complex IV [COX], two subunits of complex V [ATP] and one subunit of complex III [cyt b]) in control and siRNA treated cells. (E) Detail of a mitochondrial pulse-labeling experiment showing a severe decrease in the translation of ATP6 and ATP8 in TRUB2 depleted cells.",
    "ncbi_link": "TRUB2: 26995"
  },
  {
    "caption": "A, B. Identification of mitochondrial ribosomal proteins and pseudouridine synthase interacting proteins by sucrose gradient centrifugation in control cells (A) Individual fractions were separated by SDS-PAGE and immunoblotted with the indicated antibodies. The migration of the mt-SSU (28S), the mt-LSU (39S) and the mitochondrial monosome (55S) are shown.",
    "ncbi_link": "28S: 100008589///106632264///106632265///106632266///106632267"
  },
  {
    "caption": "A, B. Identification of mitochondrial ribosomal proteins and pseudouridine synthase interacting proteins by sucrose gradient centrifugation in cells treated with siRNA (B). Individual fractions were separated by SDS-PAGE and immunoblotted with the indicated antibodies. The migration of the mt-SSU (28S), the mt-LSU (39S) and the mitochondrial monosome (55S) are shown.",
    "ncbi_link": "28S: 100008589///106632264///106632265///106632266///106632267"
  },
  {
    "caption": "C. Quantification of the levels of the mt-SSU (28S), the mt-LSU (39S) and the mitochondrial monosome (55S) normalized to the SDHA levels. The graph represents the relative abundance of individual subunits in cells treated with specified siRNA versus controls. The bars represent the mean ± SEM.",
    "ncbi_link": "28S: 100008589///106632264///106632265///106632266///106632267"
  },
  {
    "caption": "(A, B) Representative Western blot (A) and quantification (B) of p62 associated with mitochondria from spinal cords. Protein levels are normalized by subunit ATPβ of mitochondria (Complex V). Mitochondrial p62 levels are increased at 120 days (symptomatic stage) in SOD1-G93A spinal cord relative to Non Tg and wild type SOD1 (wtSOD1). Results are expressed as mean ± SEM relative to Non Tg at 30 days; n=8 mice (4 males and 4 females). At 120 days, **p= 0.0018 (Non Tg vs. SOD1-G93A) and **p= 0.0011 (SOD1-G93A vs. wtSOD1) by paired one-way ANOVA with Tukey's correction. No other statistically significant differences were found (paired Friedman's test with Dunn's correction at 30 days and paired one-way ANOVA with Tukey's correction at 60 and 90 days).",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(C, D) Representative Western blot (C) and quantification (D) of Tim23 in homogenates from spinal cords using β-actin as normalizer. Results are expressed as mean ± SEM and relative to Non Tg at 30 days; n=6 mice (3 males and 3 females). ***p= 0.0002 (Non Tg vs. SOD1-G93A at 120 days) by paired one-way ANOVA with Tukey's correction. No other statistically significant differences were found (paired Friedman's test with Dunn's correction at 30 days and paired one-way ANOVA with Tukey's correction at 60 and 90 days). Tim23 is decreased in SOD1-G93A spinal cord relative to Non Tg at 120 days.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(E, F) Western blot (E) and quantification (F) of COXI in homogenates from spinal cords. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and relative to Non Tg at 30 days; n=6 mice (3 males and 3 females). *p= 0.017 (Non Tg vs. SOD1-G93A at 120 days) by paired Friedman's test with Dunn's correction. No other statistically significant differences were found (paired Friedman's test with Dunn's correction at 30 and 60 days and paired one-way ANOVA with Tukey's correction at 90 days). COX1 is decreased in SOD1-G93A spinal cord relative to Non Tg at 120 days.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "G) qPCR (fold change) of PGC1α mRNA normalized by β-actin mRNA. Results are expressed as mean ± SEM and fold change of Non Tg at 30 days; n= 6 (3 males and 3 females) for 30 and 120 days, n= 4 (2 males and 2 females) for 60 days and n= 5 (3 males and 2 females) for 90 days. *p= 0.035 at 90 days and ***p= 0.0007 at 120 days. Paired Student's t test (for 60, 90 and 120 days) and paired Wilcoxon's test (for 30 days) were used for comparisons.",
    "ncbi_link": "β-actin: 11461
PGC1α: 19017"
  },
  {
    "caption": "A) Representative images of mt-Keima expressing spinal cord sections of SOD1-G93A and Non Tg mice at 90 days. Mt-Keima fluorescence with excitation at 458nm is pseudocolored in green and at 543nm is pseudocolored in red. Emissions were recorded sequentially at 600-650nm. Scale bar, 150 µm.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "B) Representative images of mt-Keima expressing motor neurons in the ventral horn of SOD1-G93A and Non Tg mice at 90 days, imaged and pseudocolored Scale bar, 20 µm.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "C) Quantification of the rate of mitophagy in motor neurons expressed as the percentage of area with high ratio (543/458nm) signal normalized by the total mitochondria area. Data were collected from mice at 60 days (n= 3, 1 male and 2 females), 90 days (n= 4, 2 males and 2 females), and 120 days (n= 4, 2 males and 2 females). Number of neurons imaged: 60 days, n= 77 Non Tg and 87 SOD1-G93A; 90 days, n= 118 Non Tg and 173 SOD1-G93A; 120 days, n= 110 Non Tg and 130 SOD1-G93A. Comparisons within pairs showed that mitophagy is increased in SOD1-G93A spinal cords at 60 and 90 days compared to Non Tg. Results are expressed as mean ± SEM. For 60 days, **p= 0.0022; for 90 days, ***p= 0.0001; for 120 days, p= 0.094, all by unpaired Mann-Whitney test. Comparisons along time showed that mitophagy increases over time in both genotypes. For Non Tg, by unpaired Kruskal-Wallis's test with Dunn's correction, **p= 0.0046 and ***p= 0.0001. For SOD1-G93A, by unpaired Kruskal-Wallis's test with Dunn's correction, **p=0.0077 and *** p= 0.0001.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "Representative Western blot (A) of Parkin levels in spinal cord homogenates. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and relative to Non Tg control at 30 days; n= 8 (4 males and 4 females). Parkin levels are decreased in SOD1-G93A at 90 and 120 days compared to Non Tg.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "quantification (B) of Parkin levels in spinal cord homogenates. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and relative to Non Tg control at 30 days; n= 8 (4 males and 4 females). Paired Wilcoxon's test at 90 days, **p= 0.0078; paired Student's t test at 120 days, **p= 0.0054. Paired Wilcoxon's test for 30 and 60 days showed no statistically significant differences. Parkin levels are decreased in SOD1-G93A at 90 and 120 days compared to Non Tg.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "C) qPCR (fold change) of Parkin mRNA normalized by β-actin mRNA. Results are expressed as mean ± SEM and fold change relative to Non Tg at 30 days of age; n= 6 (3 males and 3 females) for 30 and 120 days, n= 4 (2 males and 2 females) for 60 days and n= 5 (3 males and 2 females) for 90 days. No statistically significant differences were found by paired Student's t test (90 days) and Wilcoxon's test (30, 60 and 120 days).",
    "ncbi_link": "β-actin: 11461
Parkin: 50873"
  },
  {
    "caption": "D, E) Representative Western blot (D) and quantification (E) of Parkin levels in spinal cord mitochondria at 120 days. Protein levels are normalized by Complex V. Parkin is reduced in spinal cord mitochondria of SOD1-G93A mice at 120 days. Results are expressed as mean ± SEM and shown as percent of Non Tg; n=8 (4 males and 4 females); **p= 0.0078, by Wilcoxon's t test.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "C) Quantification of SOD1 at 130 days indicates that Parkin knockout does not affect the levels of transgenic mutant human SOD1 expressed in SOD1-G93A spinal cord. Results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females); no statistically significant differences relative to SOD1 expression were found between G93A and PKO/G93A, p= 0.214, by paired Student's t test. Differences between Non Tg and G93A (by paired Friedman's test with Dunn's correction), *p= 0.020 and PKO and PKO/G93A (by paired one-way ANOVA with Tukey's correction), ***p= 0.0001.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "A) Kaplan-Meier survival analysis (Log-Rank test with Holm-Sidak's correction for multiple comparisons). Mean age of death (± SEM) for G93A was 169.3 ± 2.5 days and for PKO/G93A was 185.6 ± 2.2 days, indicating that Parkin knockout prolongs lifespan of SOD1-G93A mice; n=19 for Non Tg (9 males and 10 females), n= 20 for PKO (10 males and 10 females), n= 18 for G93A (8 males and 10 females) and n= 19 for PKO/G93A (9 males and 10 females); p= 0.0000285.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "B) Body weight changes over time, relative to body weight at 45 days that is set at 100% for each mouse. Parkin knockout delays body weight loss in SOD1-G93A mice. Results are expressed as mean ± SEM; n=19 for Non Tg (9 males and 10 females), n=20 for PKO (10 males and 10 females), n=18 for G93A (8 males and 10 females) and n=19 for PKO/G93A (9 males and 10 females); *p= 0.017 (at 150 days), *p= 0.004 (at 164 days), *p= 0.002 (at 171 days) and **p= 0.001 (at 178 days), by two-way ANOVA with repeated measures and with Holm-Sidak's correction for multiple comparisons.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "C) Clasping score changes over time. Parkin knockout does not affect clasping onset in SOD1-G93A mice. An intermediate score of 2.5 is indicated by the dotted line. Results are expressed as mean ± SEM; n=19 for Non Tg (9 males and 10 females), n=20 for PKO (10 males and 10 females), n=18 for G93A (8 males and 10 females) and n=19 for PKO/G93A (9 males and 10 females).",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "E) Quantification of the percentage of innervated NMJs at 130 days indicates that Parkin knockout decreases denervation in SOD1-G93A mice. Results are expressed as mean ± SEM and were collected from n= 6 mice per group (3 males and 3 females); n of images evaluated = 49 for Non Tg (with 483 NMJs counted), 46 for PKO (396 NMJs counted), 47 for G93A (413 NMJs assessed) and 38 for PKO/G93A (325 NMJs counted); ***p= 0.0001, by unpaired Mann-Whitney test.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "F) Representative images of lumbar spinal cord sections at 130 days immunostained with ChAT. Scale bar, 200 µm. G) Quantification of ChAT-positive MN in the spinal cord ventral horn (dotted areas) at 130 days shows that Parkin knockout decreases MN loss in the spinal cord of SOD1-G93A mice. Results are expressed as mean ± SEM; n = 10 mice per group in Non Tg, PKO and G93A (5 males and 5 females) and n= 9 for PKO/G93A (4 males and 5 females); *p=0.031, by unpaired Student's t test. H ",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "H) Representative images of lumbar spinal cords sections immunostained for GFAP at 130 days. Scale bar, 200 µm. I) Quantification of the average GFAP staining intensity at 130 days indicates that Parkin knockout decreases spinal cord astrogliosis in SOD1-G93Amice. Results are expressed as mean ± SEM; n = 10 mice per group (5 males and 5 females); *p= 0.033, by paired Student's t test.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "C) qPCR (fold change) of PGC1α mRNA normalized by β-actin mRNA at 130 days of age. Results are expressed as mean ± SEM and as fold change of the Non Tg; n= 8 (4 males and 4 females). No statistically significant differences were found between G93A and PKO/G93A (p= 0.250 by paired Wilcoxon's test); *p= 0.035 paired Friedman's test with Dunn's correction (Non Tg vs. G93A). No other statistically significant differences were found. D) qPCR (fold change) of PGC1α mRNA normalized by β-actin mRNA at end stage. Results are expressed as mean ± SEM and as fold change of the Non Tg; n= 8 (4 males and 4 females). No statistically significant differences were found between G93A and PKO/G93A (p= 0.613 by paired Student's t test). **p= 0.0058 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A comparison) and ***p<0.0001 by paired one-way ANOVA with Tukey's correction (for PKO vs. PKO/G93A comparison). Parkin knockout improves PGC1α expression at 130 days (C) but the effect is lost at end stage (D). E ",
    "ncbi_link": "β-actin: 11461
PGC1α: 19017
Parkin: 50873"
  },
  {
    "caption": "E, F) Representative Western blots (E) and quantification (F) of PARIS at disease end stage. Protein levels are normalized by β-actin and results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females). No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.99). PARIS levels are unchanged in SOD1-G93A mice relative to Non Tg at disease end stage.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "A, B) Western blots (A) and quantification (B) of Miro1 in spinal cord homogenates at disease end stage. β-actin is used as loading reference. Results are expressed as mean ± SEM and as percent of Non Tg; n = 8 (4 males and 4 females) mice per group; *p= 0.011 by paired Student's t test (for comparison G93A vs. PKO/G93A) and **p= 0.003 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A). Parkin knockout increases the levels of Miro1 in SOD1-G93A mice at disease end stage.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "C, D) Western blots (C) and quantification (D) of Mfn2 in spinal cord homogenates at disease end stage. Protein levels are normalized by β-actin. Results are expressed as mean ± SEM and as percent of Non Tg; n= 8 (4 males and 4 females) mice per group; No statistically significant differences were found between G93A and PKO/G93A (p=0.078 by paired Wilcoxon's test); ***p= 0.0007 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A) and *p= 0.037 by paired Friedman's test with Dunn's correction (for PKO vs. PKO/G93A). Parkin knockout increases the levels of Mfn2 in SOD1-G93A mice at disease end stage.",
    "ncbi_link": "Parkin: 50873
SOD1: 6647"
  },
  {
    "caption": "E) Western blots of spinal cord mitochondria at disease end stage, probed for lysine 48 (left panel) and lysine 63 (right panel) ubiquitin chains. Citrate synthase is used as loading control. Asterisks indicate ubiquitinated proteins with different abundance in SOD1-G93A samples.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "F, G) Representative Western blot (F) and quantification (G) of LC3 II in spinal cord mitochondria at end stage. Protein levels are normalized by Complex V. LC3 II is increased in both G93A and PKO/G93A mitochondria and Parkin knockout does not affect LC3 II levels. Results are expressed as mean ± SEM and as percent of Non Tg; n = 8 (4 males and 4 females) mice per group; No statistically significant differences were found between G93A and PKO/G93A (p=0.504 by paired Student's t test). *p= 0.035 by paired Friedman's test with Dunn's correction (for Non Tg vs. G93A) and **p= 0.0014 by paired one-way ANOVA with Tukey's correction (for PKO vs. PKO/G93A)",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "I) Quantification of March5 at disease end stage. Results are expressed as mean ± SEM and percent of Non Tg; n= 8 (4 males and 4 females) mice per group. No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.742). Protein levels are normalized by Complex V. March5 levels are unaffected by Parkin knockout.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "J) Quantification of Mul1 at disease end stage. Results are expressed as mean ± SEM and percent of Non Tg; n= 8 (4 males and 4 females) mice per group. No statistically significant differences were found between G93A and PKO/G93A by paired Wilcoxon's test (p= 0.94). Protein levels are normalized by Complex V. Mul1 levels are unaffected by Parkin knockout.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "GPS reporter cells expressing peptide libraries ending with a random (X) or Gly (G) residue were treated with dominant-negative (DN) cullins and analyzed. Data are presented as mean ± standard deviation from nine replicates. GPS reporter cells carrying indicated libraries were treated with shRNAs against various BC-box proteins and analyzed. VHL and FEM1C serve as unrelated BC-box protein controls. Data are presented as mean ± standard deviation from nine replicates.",
    "ncbi_link": "FEM1C: 56929
VHL: 7428"
  },
  {
    "caption": "(G) Confocal images of U2OS cells expressing MTSGLUL-GFP proteins with or without a C-terminal diGly degron. MitoTracker staining shows mitochondria. Scale bar = 20 µm. (H) Confocal images of U2OS cells expressing MTSGLUL-GFP-diGly degron fusion proteins co-stained with MitoTracker, and with or without DNCul2 treatment. Scale bar = 20 µm.",
    "ncbi_link": "Cul2: 8453"
  },
  {
    "caption": "Fractionation and Western blot analysis of wild-type and Flag-tagged PDP2 (top), and wild-type and MTS-deleted (∆MTS) MRPL28 (bottom). Flag-PDP2 and ∆MTS MRPL28 were mislocalized. W, C, and M denote whole cell lysates, cytosol fraction and mitochondrial fraction, respectively. Tubulin and VDAC serve as fractionation quality controls.",
    "ncbi_link": "Flag: 
MRPL28: 10573
PDP2: 57546"
  },
  {
    "caption": "Fractionation analysis of wild-type HA-MIC19 in U2OS cells treated with IMP-1088 and with or without inhibition of ZYG11B or KLHDC2. The normalized relative abundance of cytosolic HA-MIC19/tubulin is indicated under each lane in red.",
    "ncbi_link": "ZYG11B: 79699"
  },
  {
    "caption": "GST pull-down assay using cells expressing GST or GST-tagged wild-type or mutant KLHDC2 and HA-tagged SDE2, FAU or TUG.",
    "ncbi_link": "KLHDC2: 23588"
  },
  {
    "caption": "B. Rapamycin suppresses TLR3-stimulated IFNβ mRNA production in cultured macrophages: RAW264.7 macrophages were treated as above but stimulated -/+poly (I:C) [30 μg/ml] for 3 hr. q-RT-PCR measured IFNβ gene expression. Results represent the mean +/- SD of triplicate samples from one experiment. *p=.03 relative to no Poly(I:C) by paired t-test (one-tailed); **p=.04 relative to +Poly (I:C) by paired t-test (one-tailed).",
    "ncbi_link": "IFNβ: 15977"
  },
  {
    "caption": "Western blot for phosphorylated and total ERK in HEK293 cells transfected with native and ΔA781_N783 (left) or P824R (right) CSF-1R and treated with CSF-1 (D, E) or IL-34 (F, G) for 10 minutes. Horizontal line indicates untreated cells, with increasing concentrations 10, 50 and 100 ng/ml. Corresponding densitometry displays the ratio of phospho-ERK to total ERK, normalised to the ratio of the untreated control for the native receptor (**** p < 0.0001, *** p < 0.0005, ** p < 0.01, * p < 0.05, one-way ANOVA with Sidak's post-test for multiple comparison, n = 3 biological replicates, , error bars indicate SEM).",
    "ncbi_link": "CSF-1R: 1436"
  },
  {
    "caption": "Western blot for CSF-1R in HEK293 cells transfected with native and ΔA781_N783 (top) or P824R (bottom) CSF-1R and treated with rapamycin. Horizontal line indicates untreated cells, with concentrations 0.1, 0.5, 1, 5, 10μM. Corresponding densitometry (below) displays the fold change of CSF-1R relative to the untreated control for each transfection (**** p < 0.0001, one-way ANOVA with Sidak's post-test for multiple comparison to untreated, n = 3 biological replicates, error bars indicate SEM). Western blot for CSF-1R in HEK293 cells transfected with native and ΔA781_N783 (top) or P824R (bottom) CSF-1R and treated with 3-methyladenosine. Horizontal line indicates untreated cells, with increasing concentrations 0.1, 0.2, 0.5, 1mM. Corresponding densitometry (below) displays the fold change of CSF-1R relative to the untreated control for each transfection (**** p < 0.0001, * p = 0.0114, one-way ANOVA with Sidak's post-test for multiple comparison to untreated, n = 3 biological replicates, error bars indicate SEM). Western blot for CSF-1R and Actin in HEK293 cells transfected with native and ΔA781_N783 (top) or P824R (bottom) CSF-1R and treated with MG132 or PLX3397. Horizontal line indicates untreated cells, 20μM PLX3397, with increasing concentrations 0.1, 0.5, 0.1, 5μM. Corresponding densitometry (below) displays the fold change of CSF-1R relative to the untreated control for each transfection (*** p = 0.0002, ** p = 0.002, one-way ANOVA with Sidak's post-test for multiple comparison to untreated, n = 3 biological replicates, error bars indicate SEM).",
    "ncbi_link": "CSF-1R: 1436"
  },
  {
    "caption": "Immunocytochemistry of microglia isolated from Csf-1rflx/wt;Cx3cr1-Cre- and Csf-1rflx/wt;Cx3cr1-Cre+ P0 mouse pup brains. Microglia were stimulated with LPS and exposed to fluorescent opsonised latex beads for 1 hour before fixation and quantification of bead+ cells via microscopy. Cells were stained using MitoTracker(red). Arrowheads (white) indicate bead+ cells. Quantification of mouse microglial phagocytic activity expressed as percentage bead+ cells (n = 4 assays, error bars indicate SEM).",
    "ncbi_link": "Cre: 2777477
Csf-1r: 12978
Cx3cr1: 13051"
  },
  {
    "caption": "L) Immunocytochemistry of macrophages differentiated in vitro from Csf-1rflx/wt;Cx3cr1-Cre- and Csf-1rflx/wt;Cx3cr1-Cre+ mouse bone marrow. Macrophages were stimulated with LPS and exposed to fluorescent opsonised latex beads for 1 hour before fixation and quantification of bead+ cells via microscopy. Cells were stained using MitoTracker (red) and DAPI (blue). Arrowheads (white) indicate bead+ cells. M) Quantification of mouse macrophage phagocytic activity expressed as percentage bead+ cells. (* p = 0.024, Student's t-test with Welch's correction, n = 4 assays, error bars indicate SEM).",
    "ncbi_link": "Cre: 2777477
Csf-1r: 12978
Cx3cr1: 13051"
  },
  {
    "caption": "A) Immunohistochemistry of Csf-1rflx/wt;Cx3cr1-Cre- (top) and Csf-1rflx/wt;Cx3cr1-Cre+ (bottom) mice unilaterally injected with Aβ1-42 in the hippocampus and stained for IB4 (green), F4/80 (white) and Aβ (red). Scale bars indicate 50 μm. B) Quantification of F4/80 and IB4 immunopositivity following intrahippocampal injection of Aβ1-42. Quantification of immunopositivity in both injected and uninjected hippocampi of Csf-1rflx/wt;Cx3cr1-Cre- and Csf-1rflx/wt;Cx3cr1-Cre+ mice. (Two-way ANOVA with Sidak's test for multiple comparisons. Asterisks (*) indicate comparison to immunopositivity values of the uninjected hippocampus, obliques (#) indicate comparison between Csf-1rflx/wt;Cx3cr1-Cre- and Csf-1rflx/wt;Cx3cr1-Cre+ mice, ## or ** p < 0.003, #### or **** p < 0.0001, n = 5 mice per group,error bars indicate SEM).",
    "ncbi_link": "Cre: 2777477
Csf-1r: 12978
Cx3cr1: 13051"
  },
  {
    "caption": "C) Immunohistochemistry of Csf-1rflx/wt;Tie2-Cre- (top) and Csf-1rflx/wt;Tie2-Cre+ mice (ottom) mice unilaterally injected with Aβ1-42 in the hippocampus and stained for IB4 (green), F4/80 (white) and Aβ (red). D) Quantification of F4/80 and IB4 immunopositivity following intrahippocampal injection of Aβ1-42. Quantification of immunopositivity in both injected and uninjected hippocampi of Csf-1rflx/wt;Tie2-Cre- and Csf-1rflx/wt;Tie2-Cre+ mice. (n = 5 mice per group. Two-way ANOVA with Sidak's test for multiple comparisons. Asterisks (*) indicate comparison to immunopositivity values of the uninjected hippocampus, *p < 0.01, *** p < 0.0005, error bars indicate SEM)).",
    "ncbi_link": "Cre: 2777477
Csf-1r: 12978
Tie2: 21687"
  },
  {
    "caption": "qPCR of wild type (blue) or Csf-1r+/- (red) endothelial cells treated with control, Csf-1r+/+ MCM or Csf-1r+/- MCM. Statistical analyses of inter-genotype changes. (**** p < 0.0001, ** p < 0.005, Scatter plots represent technical replicates of n = 2 independent primary cell isolations and microglia conditionings, Two-way ANOVA with multiple comparisons and Sidak post-test, error bars indicate SEM)).",
    "ncbi_link": "Csf-1r: 12978"
  },
  {
    "caption": "IHC of ALSP patient post mortem tissue for amyloid-β (green) and CLD5 (red), (B) human IgG (green) and PDGFRβ (red), (C) GFAP (green) and CLD5 (red). ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "ncbi_link": "CSF-1R: 1436"
  },
  {
    "caption": "(D) Iba1 (green) and GFAP (red), (E) amyloid-β (green) and CD68 (red), (f) CD163 (green) and CLD5 (red), imaging of an ALSP patient with the ΔA781_N783 CSF-1R variant. ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "ncbi_link": "CSF-1R: 1436"
  },
  {
    "caption": "(G) Fibrinogen (green) and CLD5 (red) and (H) FLAIR imaging of an ALSP patient with the ΔA781_N783 CSF-1R variant. ΔA781_N783 and P824R indicate the CSF-1R variant present.",
    "ncbi_link": "CSF-1R: 1436"
  },
  {
    "caption": "RIP-qPCR for the indicated RNA (AsGFP or NORAD) in cells transfected with the AcGFP bearing NucLibB in the 3' UTR, with RIP performed with the indicated antibody and RNA levels determined by qRT-PCR. N=5. Error bars - s.e.m.",
    "ncbi_link": "AcGFP: 
AsGFP: 
NORAD: 647979"
  },
  {
    "caption": "(B) Screen shots from the UCSC genome browser showing signal profiles of p53 mRNA immunoprecipitated by anti-EZH2 antibody in LNCaP and C4-2 cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) C4-2 cells were subjected to UV-RIP assay. RT-qPCR measurement of p53 mRNA immunoprecipitated by IgG or anti-EZH2 antibody. Data shown as means ± SD (n=3). Statistical significance was determined by two-tailed Student's t-test. ** P<0.01.",
    "ncbi_link": "IgG: 
p53: 7157"
  },
  {
    "caption": "(E) Top, RT-qPCR analysis of p53 mRNA in C4-2 cell lysate pulled down by GST or GST-EZH2 recombinant proteins EZ1-EZ4. Bottom, western blotting analysis of GST or GST-EZH2 proteins used for GST pull-down assay. Asterisks indicate the protein bands at expected molecular weight. Data shown as means ± SD (n=3). Statistical significance was determined by two-tailed Student's t-test.** P<0.01.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) C4-2 cells were transfected with Myc-tagged EZH2-WT or EZH2-∆336-554 for 24 h and cells were harvested for RIP with IgG or anti-Myc tag antibody. Transfected proteins and pull-down p53 mRNAs were analyzed by western blot and RT-qPCR, respectively. Data shown are means ± SD (n=3). * P<0.01. ERK2, a loading control.",
    "ncbi_link": "EZH2: 2146
p53: 7157"
  },
  {
    "caption": "(G) GST pull-down assay using in vitro transcribed different fragments of p53 mRNA and indicated GST proteins followed by RT-qPCR analysis of pull-down p53 mRNA. FL, full length; ORF, open reading frame; UTR, untranslated region.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(H, I) RNA EMSA evaluation of EZh2 binding of p53 mRNA. GST-EZH2 recombinant proteins (EZ1 to EZ4) were incubated with biotin-labeled in vitro transcribed p53 5'UTR (biotin-labeled probe) in the presence or absence of 100-fold unlabeled p53 5'UTR (unlabeled probe), followed by PAGE and immune blotting with HPR-conjugated streptavidin.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) Biotin pull down assay by incubating biotin-labelled different fragments of p53 mRNA and HOTAIR (positive control) with C4-2 cell lysate followed by western blot with EZH2 antibody.",
    "ncbi_link": "HOTAIR: 100124700
p53: 7157"
  },
  {
    "caption": "(B) Biotin pull down assay as in (A) using unmutated and various internally deleted mutants of 5'UTR of p53 mRNA. Top, diagram of different p53 5'UTR deletion mutants.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) Upper, the linear map of the pRF bicistronic report plasmid. The SV40 promoter (purple box) was used to drive firefly luciferase (Fluc) and Renilla luciferase (Rluc) gene transcription. Different p53 5'UTR fragments were inserted between the Fluc and Rluc genes. Lower, at 24 h after transfection, cells were lysed and luciferase activities were measured using a dual-luciferase kit and the ratio of Fluc/Rluc was calculated. Data shown as means±SD (n=3). Statistical significance was determined by two-tailed Student's t-test. * P<0.01.",
    "ncbi_link": "Fluc: 
luciferase: 
Rluc: 
p53: 7157"
  },
  {
    "caption": "(D) EZH2 knockdown C4-2 cells were transfected with the bicistronic reporter vector in combination with empty vector, Myc-tagged EZH2 WT or deletion mutants followed by western blot analysis with indicated antibodies (bottom) and luciferase assay (top). Data shown as means±SD (n=3). * P<0.01.",
    "ncbi_link": "EZH2: "
  },
  {
    "caption": "(E) C4-2 and U2OS cell lines were transfected with non-specific control (siC) or two independent EZH2-specific siRNAs and harvested for western blot analysis with indicated antibodies. ERK2 and β-TUBULIN, loading controls.",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": "(F) U2OS cells were transfected with control (siC) or EZH2-specific siRNAs and treated with 200 nM of CPT followed by western blot analysis for indicated proteins.",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": "(G) C4-2 cells were transfected with control (siC) or EZH2-specific siRNAs and plasmids for empty vector, EZH2 WT or deletion mutants followed by western blot analysis for indicated proteins.",
    "ncbi_link": "EZH2: 
EZH2: 2146"
  },
  {
    "caption": "(C) Co-IP of endogenous EZH2 with eIF4G2 or PABP1 from C4-2 cell lysate pre-treated with RNaseA in 37oC for 30 min. The effectiveness of RNaseA treatment was monitored by RT-PCR analysis of the presence of GAPDH mRNA.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(D) C4-2 cells were transfected control (siC) or EZH2-specific siRNA and lysed for polysome fractionation. RNA was extracted from even-number fractions followed by RT-qPCR analysis for p53 and GAPDH mRNA. The β-ACTIN mRNA was used as an internal control. Data shown as means±SD (n=3). Statistical significance was determined by two-tailed Student's t-test. * P<0.01; NS, no significance.",
    "ncbi_link": "β-ACTIN: 
EZH2: 2146
GAPDH: 2597
p53: 7157"
  },
  {
    "caption": "(E) C4-2 cells were transfected with control (siC) or EZH2-specific siRNAs in combination with empty vector, EZH2 WT or different deletion mutants followed by polysome fractionation and RT-qPCR. β-ACTIN mRNA was used as an internal control. Data shown as means±SD (n=3). * P<0.01.",
    "ncbi_link": "EZH2: 
β-ACTIN: 
EZH2: 2146"
  },
  {
    "caption": "(A) IHC analysis of Pten, Ezh2 and p53 proteins in prostatic tissues of 4-month-old mice with different genotypes: Ptenpc-/- (n=11); Ezh2pc-/- (n=8); Ptenpc-/-;Ezh2pc-/- (n=10) and 'wild-type' littermate controls (n=10). Scale bars, 50",
    "ncbi_link": "Ezh2: 14056
Pten: 19211"
  },
  {
    "caption": "(C) Analysis of correlation of Ezh2 and p53 protein levels determined by IHC in Pten knockout (Ptenpc-/-) mice (n=11).",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "(D) RT-qPCR analysis of p53 mRNA expression in four different genotypes of mice as described Statistical significance was determined by two-tailed Student's t-test. * P<0.01.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(E) RT-qPCR analysis of mRNA expression of p53 downstream target gene Bax in four different genotypes of mice as indicated. Statistical significance was determined by two-tailed Student's t-test. * P< 0.01.",
    "ncbi_link": "Bax: 12028
p53: 22059"
  },
  {
    "caption": "(A) Correlation analysis of EZH2 and p53 mRNA expression measured by RT-qPCR in primary and metastatic prostate cancer specimens of a cohort of patients from University of Washington.",
    "ncbi_link": "EZH2: 2146
p53: 7157"
  },
  {
    "caption": "(A, B) VCaP cells stably expressing control (sh-control) or p53-specific shRNA were infected with lentivirus for empty vector (EV) or deletion mutants of EZH2. Cell growth in 2D (A) and 3D (B) conditions were determined by MTS assay and measurement of clone size, respectively. Statistical significance was determined by two-tailed Student's t-test. * P < 0.05, *** P < 0.001.",
    "ncbi_link": "EZH2: 
p53: 7157"
  },
  {
    "caption": "(B) Kaplan-Meier plots showing the association of EZH2 overexpression with biochemical recurrence of prostate cancer in patients from the TCGA cohort. Tumors were separated into two groups according to EZH2 expression levels (high or low) and three groups based on the mutation status of p53 (WT, loss or mutated).",
    "ncbi_link": "EZH2: 2146
p53: 7157"
  },
  {
    "caption": "VCaP and C4-2 cells were treated with GSK-126, DZNep (5 µM for VCaP and 10 µM for C4-2), and EZH2 ASO, followed by western blots with indicated antibodies (C) Data shown as means±SD (n=6). Statistical significance was determined by two-tailed Student's t-test. *** P < 0.001.",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": "VCaP and C4-2 cells were treated with GSK-126, DZNep (5 µM for VCaP and 10 µM for C4-2), and EZH2 ASO, followed by MTT assay (D). Data shown as means±SD (n=6). Statistical significance was determined by two-tailed Student's t-test. *** P < 0.001.",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": "(E, F) Effect of Ezh2 ASOs on growth of murine prostate cancer allografts. Mice (n=10) bearing the Ptenpc-/-;Trp53pc-/- (E) and Ptenpc-/-;Trp53pc-/R172H allografts (F) were treated with control ASOs (50 mg kg-1) or Ezh2 ASOs at different doses (25 mg kg-1 and 50 mg kg-1). Tumor growth was measured twice a week for 3 weeks and the data are shown in the bottom panels. Each allograft was isolated by the end of ASO treatment and photographed (top panels). Data shown as means±SD (n=10). Statistical significance was determined by two-tailed Student's t-test. *** P < 0.001.",
    "ncbi_link": "Ezh2: 14056
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "(E) Age‑associated changes in YBX1 levels in human BMSCs from 30 males (left panel) and 30 females (right panel).",
    "ncbi_link": "YBX1: 4904"
  },
  {
    "caption": "(F and G) Representative images of Alizarin Red staining (F) and quantification of calcification (G) by detecting the amount of Alizarin Red extracted from the matrix in BMSCs transfected with adenovirus driven control and Ybx1 shRNA at 21 days of osteogenic induction.",
    "ncbi_link": "Ybx1: 22608"
  },
  {
    "caption": "(L-M) Relative mRNA levels of osteogenic differentiation related genes (L), adipogenic differentiation and senescence related genes (M) between BMSCs transfected with adenovirus driven control and Ybx1 shRNA.",
    "ncbi_link": "Ybx1: 22608"
  },
  {
    "caption": "(B-F) Representative μCT images, Scale bar: 1mm. (B) and quantitative μCT analysis of trabecular bone microarchitecture (C-F) in distal femora from 3- and 12-month-old male Ybx1Prx1-CKO mice and Ybx1flox/flox mice (BV/TV, bone volume per tissue volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation).",
    "ncbi_link": "Prx1: 19153
Ybx1: 22608"
  },
  {
    "caption": "(E-F) Representative μCT images, Scale bar: 1mm. (E) and quantitative μCT analysis of trabecular bone microarchitecture (F) in distal femora from 24-month-old mice with rAAV8-GFP-Ybx1 or rAAV8-GFP transfection (BV/TV, bone volume per tissue volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation).",
    "ncbi_link": "GFP: 
Ybx1: 22608"
  },
  {
    "caption": "(C) Semi-quantitative PCR showing the different isoforms of Fn1, Nrp2, Sp7, and Sirt2 from BMSCs of Ybx1Prx1-CKO mice and Ybx1flox/flox mice.",
    "ncbi_link": "Fn1: 14268
Nrp2: 18187
Prx1: 19153
Sirt2: 64383
Sp7: 170574
Ybx1: 22608"
  },
  {
    "caption": "(D-G) Representative images of Alizarin Red staining (D and F) and quantification of calcification by detecting the amount of Alizarin Red extracted from the matrix (E and G) in BMSCs transfected with different isoforms of Sp7 or different isoforms of Spp1.",
    "ncbi_link": "Sp7: 170574
Spp1: 20750"
  },
  {
    "caption": "(H-I) Representative images (H) and quantification of Oil Red O staining (I) in BMSCs transfected with different isoforms of Spp1 with 10 days of adipogenic induction.",
    "ncbi_link": "Spp1: 20750"
  },
  {
    "caption": "(J-K) Representative images of β-Gal staining (J) and quantification (K) of β-Gal positive cells in BMSCs transfected with different isoforms of Sirt2.",
    "ncbi_link": "Sirt2: 64383"
  },
  {
    "caption": "(L-T) BMSCs were isolated from Ybx1Prx1-CKO mice and Ybx1flox/flox mice, among them, the BMSCs from Ybx1flox/flox mice were transfected with the blank control, BMSCs from Ybx1Prx1-CKO mice were transfected with the blank control or different isoforms of the target genes. (L-P) Representative images of Alizarin Red staining (L and O) and quantification of calcification by detecting the amount of Alizarin Red extracted from the matrix (M and P). (Q-R) Representative images (Q) and quantification of Oil Red O staining (R) in BMSCs after 10 days of adipogenic induction. (S-T) Representative images of β-Gal staining (S) and quantification (T) of β-Gal positive cells among BMSCs.",
    "ncbi_link": "Prx1: 19153
Ybx1: 22608"
  },
  {
    "caption": "(K) Co-IP of His-FBXO33 with HA-YBX1 and a series of mutant HA-YBX1 proteins following transfection into BMSCs.",
    "ncbi_link": "HA: 
YBX1: 22608"
  },
  {
    "caption": "(N) Semi-quantitative PCR showed the isoforms of Fn1, Nrp2 and Sirt2 in cultured BMSCs isolated from 2-month-old or 24-month-old mice then treated with or without sciadopitysin.",
    "ncbi_link": "Fn1: 14268
Nrp2: 18187
Sirt2: 64383"
  },
  {
    "caption": "F Whole-mount visualization of mitochondria  in injured hypoglossal motor axon at 5 days after injury. G Immunostaining  of injured hypoglossal nerves for GFP  and cytochrome c (Cytc) at 5 days after injury. H Number of mitochondria  in injured axons  of Atf3:BAC2 Tg and Rpt3  CKO mice  at 5 days after injury  (n= 5 mice  per group). I Total number of GFP-positive injured motor neurons  in Atf3:BAC2 Tg and Rpt3  CKO mice  at 5 days after injury  (n= 4 mice  per group). J Number of GFP-positive mitochondria  in soma  at 5 days after injury. Data are shown as the mean ± s.e.m. (n= 3 mice). Data information: Data are shown as the mean ± s.e.m., ** P = 0.0005 in (H), no significant difference (P = 0.8915) in (I) and * P = 0.0068 in (J), determined by unpaired t-test. Dashed lines reveal hypoglossal nucleus  in axon  in (F and G). Scale bars, 5 μm in (F) and 2.5 μm in (G).",
    "ncbi_link": "Atf3: 11910
Rpt3: 23996"
  },
  {
    "caption": "C Thionine-stained motor neurons  of Atf3:BAC2 Tg and Rpt3  CKO mice at 7, 14 and 17 days after hypoglossal nerve axotomy. Arrows indicate the loss of  motor neurons. D The graph showing the percentage of surviving motor neurons  on the injured  side compared with that on the control side. Data are shown as the mean ± s.e.m. (** P = 0.0002, *** P < 0.0001, determined by unpaired t-test, n = 5 mice  per group at each  time point). Data information: Dashed lines outline hypoglossal nucleus in XII, hypoglossal nucleus; cc, central canal. Scale bars, 150 μm in C)",
    "ncbi_link": "Atf3: 11910
Rpt3: 23996"
  },
  {
    "caption": "C Hypoglossal motor neurons of Atf3:BAC2 Tg and Rpt3  CKO mice  before and at 5 days (5d) and 28 days (28d) after injury, immunostained  by AnkG  and GFP. Arrows indicate the AIS stained  by AnkG. Scale bars, 20 μm. D Quantification of the number of the AIS  in control (Cont) and injured  (Inj) hypoglossal motor neurons of Atf3:BAC2 and Rpt3  CKO mice. Data are expressed as mean ± s.e.m. * P = 0.043, ** P = 0.0162, *** P = 0.008, **** P < 0.0001, determined by one-way ANOVA followed by Tukey post hoc analysis, n.d., not detected, n = 5 mice  for each group. E Quantification of the AIS  length in control (Cont) and injured  (Inj) hypoglossal motor neurons of Atf3:BAC2 and Rpt3  CKO mice. Data are expressed as mean ± s.e.m. * P = 0.0087, ** P = 0.0024, *** P = 0.0007, determined by one-way ANOVA followed by Tukey post hoc analysis, n.d., not detected, n = 5 mice  for each group.",
    "ncbi_link": "Atf3: 11910
Rpt3: 23996"
  },
  {
    "caption": "B  Ubiquitination assay of AnkG  protein. The lysates of COS-7  cells expressing the indicated truncated AnkG tagged with GST and HA-Ubiquitin  were  pulled down with glutathione Sepharose  beads, followed by western blotting with anti-HA  and anti-GST  antibodies.",
    "ncbi_link": "HA: 
Ubiquitin: 7314"
  },
  {
    "caption": "C The localization  of AnkG  and GFP-labeled mitochondria  in the AIS  of uninjured MN  of Thy1-Mito  Tg mice  and injured motor neurons of Atf3:BAC2 Tg and Rpt3  CKO mice. D Graphs show the GFP  and AnkG  fluorescent intensity scans corresponding to (C) over a 20 μm line running from the soma  to the axon. E Graph represents the percentage (%) of GFP  intensity in the AIS, compared with that in the AIS  of Thy1-Mito mouse  (n = 5 mice  per group). Data information: For (E, data are shown as the mean ± s.e.m., ** P = 0.0003, *** P < 0.0001 in (E determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. In closed arrowheads denote the presence of the AIS, while open arrowheads show disappeared AIS. Scale bars, 5 μm in C,",
    "ncbi_link": "Atf3: 11910
Rpt3: 23996
Thy1: 21838"
  },
  {
    "caption": "I Altered localization  of the GFP-labeled mitochondria  in the AIS  of injured motor neurons  of AnkG  shRNA AAV-infected Rpt3  CKO mice  at 5 days after injury. J Fluorescent intensity scans of GFP  and AnkG  corresponding to (I). K Graph represents the percentage (%) of GFP  intensity in the AIS, compared with that in the AIS  of Atf3:BAC2 Tg mouse  treated with AnkG  shRNA (n = 5 mice  per group). Data information: For data are shown as the mean ± s.e.m. , ** P = 0.0064 in (K) determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. In I), closed arrowheads denote the presence of the AIS, while open arrowheads show disappeared AIS. Scale bars, 5 μm in I)",
    "ncbi_link": "AnkG: 11735
Atf3: 11910
Rpt3: 23996"
  },
  {
    "caption": "L Thionine-stained hypoglossal motor neurons of Rpt3  CKO mice  at 10 days after injury. Rpt3  CKO mice  are infected by AnkG  shRNA or scramble shRNA AAVs. Dashed lines outline hypoglossal nucleus. XII, hypoglossal nucleus; cc,  central canal. M The percentage of surviving motor neurons on the injured  side compared with that on the control side in Rpt3  CKO mice  after infection of AnkG  shRNA or scramble shRNA AAVs  (n= 4 mice  per group). Data information: For M), data are shown as the mean ± s.e.m. , * P = 0.0405, ** P = 0.003 in (M), determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. Scale bars, 100 μm in (L).",
    "ncbi_link": "AnkG: 11735
Rpt3: 23996"
  },
  {
    "caption": "B Whole-mount visualization  of GFP- or CFP-labeled mitochondria  (mtGFP or mtCFP) in sciatic nerve. Dashed lines indicate the boundary of axon. Scale bar, 5 μm. C Representative kymographs  showing the behavior of mtCFP in uninjured sciatic nerves  of Thy1-Mito  Tg and mtGFP in injured   sciatic nerves  of Atf3;BAC2 and Rpt3  CKO mice.",
    "ncbi_link": "Atf3: 11910
Rpt3: 23996
Thy1: 21838"
  },
  {
    "caption": "C Immunostaining  of spinal cord in Atf3:BAC Tg and Atf3;SOD1 mice  at P70. The boxed regions are magnified in lower panels. Arrows indicate GFP- and ATF3- positive motor neurons (MNs). Dashed lines outline the edge of the  gray matter in  spinal cord. D The percentage (%) of GFP-positive MNs  (black bar) in ChAT-positive MNs  of Atf3:BAC and Atf3;SOD1 mice  at P70 (n = 5 mice  per each group). E The percentage (%) of ATF3, MMP-9  or osteopontin  (OPN)-positive MNs  (black bar) in GFP-positive MNs  of Atf3;SOD1 mice  at P65-70 (n = 5-7 mice  per group). Data information: For (D, E, data are shown as the mean ± s.e.m., Scale bars , 50 μm in (C; upper panel), 20 μm in (C; lower)",
    "ncbi_link": "Atf3: 11910
SOD1: 6647"
  },
  {
    "caption": "F Immunostaining  of AnkG  in ChAT-positive spinal MN  of Atf3:BAC and SOD1  and in GFP-positive spinal MN  of Atf3;SOD1 mouse  at P70. G Quantification of the AIS  length (n = 5 mice  per group). Data information: For G, data are shown as the mean ± s.e.m., no significant difference in (G) determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. Scale bars, 10 μm in (F",
    "ncbi_link": "Atf3: 11910
SOD1: 6647"
  },
  {
    "caption": "H The localization  of AnkG  and GFP-labeled mitochondria  in uninjured spinal MN  of Thy1-Mito  (without ATF3  induction), traumatically sciatic nerve-injured MN  of Atf3:BAC (with ATF3  induction) and pathologically damaged MN  of Atf3;SOD1 mice  (with ATF3  induction). Closed arrowheads denote the presence of the AIS, while open arrowheads show disappeared AIS. I Fluorescent intensity scan of GFP  and AnkG  in corresponding to (H). J The percentage (%) of GFP  intensity in the AIS, compared with that in the AIS  of uninjured MNs  in Thy1-Mito mice  (n = 5 mice  per group). Data information: For data are shown as the mean ± s.e.m. , ** P = 0.0008, *** P = 0.0007 in (J), ** determined by one-way ANOVA followed by Tukey post-hoc test, n.d., not detected. Scale bars, 5 μm in (H).",
    "ncbi_link": "ATF3: 11910
Atf3: 11910
SOD1: 6647
Thy1: 21838"
  },
  {
    "caption": "A, B Quantification of mitotic (A) and meiotic (B) cells in the distal germline in wild-type animals fed bacteria transformed with either empty vector (con) or vector-expressing dsRNA against frh-1 (frh-1) or isp-1 (isp-1) Data information: Data are presented as mean ± SE (A) N=3 at least 5 worms per replicate and condition, (B) N=3 at least 10 worms for conditio * P < 0.05 and **** P < 0.0001 vs con (One-way ANOVA Tukey\"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Quantification of apoptotic corpse in the meiotic compartment of CED-1::GF relative to the total number of meiotic cells, fed bacteria transformed with either empty-vector (con) or vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated with gamma radiation 125 Gy (A Data information: Data are presented as mean ± SEM. For each panel at least N=3 and 10 worms for replicate and condition. * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ## <0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey\"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Quantification of apoptotic corpse in the meiotic compartment of CED-1::GF relative to the total number of meiotic cells, fed bacteria transformed with either empty-vector (con) or vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated wit ), UVC 400J/m2 (B Data information: Data are presented as mean ± SEM. For each panel at least N=3 and 10 worms for replicate and condition. * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ## <0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey\"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Quantification of apoptotic corpse in the meiotic compartment o wild-type strain relative to the total number of meiotic cells, fed bacteria transformed with either empty-vector (con) or vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated wit different doses of UVB (C Data information: Data are presented as mean ± SEM. For each panel at least N=3 and 10 worms for replicate and condition. * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ## <0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey\"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Quantification of apoptotic corpse in the meiotic compartment of CED-1::GF relative to the total number of meiotic cells, fed bacteria transformed with either empty-vector (con) or vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated wit 100µM cisplatin Data information: Data are presented as mean ± SEM. For each panel at least N=3 and 10 worms for replicate and condition. * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ## <0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey\"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Time course quantification of apoptotic corpses relative to the total number of meitic cells from wild-type animals fed bacteria transformed with either vector expressing dsRNA against gfp (con) or frh-1 (A and left untreated or exposed to 1200 J/m2 UVB. Apoptotic cells were counted 12, 24 and 36 hours after exposure Data information: Data are presented as mean ± SEM, N= * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparisons",
    "ncbi_link": "gfp: 
frh-1: 174002"
  },
  {
    "caption": "Time course quantification of apoptotic corpses relative to the total number of meitic cells from wild-type animals fed bacteria transformed with either vector expressing dsRNA against gfp (con) o isp-1 (B), and left untreated or exposed to 1200 J/m2 UVB. Apoptotic cells were counted 12, 24 and 36 hours after exposure Data information: Data are presented as mean ± SEM, N= * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOV Tukey"s multiple comparisons",
    "ncbi_link": "gfp: 
isp-1: 177609"
  },
  {
    "caption": "Real Time PCR gene expression analysis of egl- genes, performed in wild-type animals fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated with gamma radiatio Data information: Data are presented a mean ± SE N= * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparisons",
    "ncbi_link": "egl-: 179943
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Real Time PCR gene expression analysis of egl- genes, performed in wild-type animals fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated wit UV Data information: Data are presented as mean ± SE N= * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparisons",
    "ncbi_link": "egl-: 179943
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Real Time PCR gene expression analysis o ced-1 genes, performed in wild-type animals fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1 and left untreated or treated with gamma radiatio Data information: Data are presented as mean ± SE N= * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparisons",
    "ncbi_link": "ced-1: 191625
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Real Time PCR gene expression analysis o ced-1 genes, performed in wild-type animals fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1 and left untreated or treate with UV Data information: Data are presented as mean ± SE N= F). * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001 vs untreated; # p < 0.05 and ## p < 0.01 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s mu comparisons test",
    "ncbi_link": "ced-1: 191625
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Representative fluorescence pictures and quantification (below the fluorescence pictures) of dissected adult gonads relative to the number of mitotic cells from wild-type animals fed bacteria transformed with either vector expressing dsRNA against gfp (con) or frh-1 and stained with DAPI (blue) and either anti-PARP-1 (red) (A Scale bar: 20µ (A Data information: Data are presented as mean ± SD. For each panel N=2, 8-10 worms per replicate and condition",
    "ncbi_link": "frh-1: 174002"
  },
  {
    "caption": "Representative fluorescence pictures and quantification (below the fluorescence pictures) of dissected adult gonads relative to the number of mitotic cells from wild-type animals fed bacteria transformed with either vector expressing dsRNA against gfp (con) or frh-1 and stained with DAPI (blue and eithe anti-RPA-1 (green) and anti-RAD-51 (red) antibodies and treated with gamma radiation (125 Gy) (B) (untreated animals displayed no staining of RPA-1 and RAD-51, not shown) 15µm (B Data information: Data are presented as mean ± SD. For each panel N=2, 8-10 worms per replicate and condition",
    "ncbi_link": "frh-1: 174002"
  },
  {
    "caption": "A, B Quantification to the number of mitotic cells of dissected gonads from wild-type animals stained with either anti-phosphohistone H3 (PH3) (A), anti-CDK-1 (CDK-1) (B) transformed with either empty vector (con) or vector-expressing dsRNA against frh-1 (frh-1) or isp-1 (isp-1) and treated with gamma radiation 125 Gy. Quantification is expressed as fold changes of positive stained cells treated over the positive untreated cells Data information: Data are presented as mean ± SD (A, B N=2 (A, B * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. One-way ANOVA Tukey"s multiple comparisons test",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Fertilit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, and left untreated or treated with gamma radiatio at the indicated doses Data information: Data are presented a mean ± SE N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified 2-wa 2-way ANOVA Tukey"s multiple compa (C-H)",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "fecundit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, and left untreated or treated wit UV at the indicated doses Data information: Data are presented a mean ± SE ), N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified , B), 2-way ANOVA Tukey"s multiple compa",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Fertilit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, and left untreated or treated wit Hydroxyure at the indicated doses Data information: Data are presented a mean ± SE N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified , B), 2-way ANOVA Tukey"s multiple comparisons",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "fecundit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, and left untreated or treated with gamma radiatio at the indicated doses Data information: Data are presented a mean ± SE N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified , B), 2-way ANOVA Tukey"s multiple compa",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "fecundit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, and left untreated or treated wit UV at the indicated doses Data information: Data are presente as mean ± SE ), N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified , B), 2-way ANOVA Tukey"s multiple compa",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "fecundit quantification of wild-type strain fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1, an left untreated or treated wit Hydroxyure at the indicated doses Data information: Data are presente as mean ± SE N= * P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 vs untreated; # P < 0.05, ### P < 0.001, ## P < 0.01, ### P < 0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified , B), 2-way ANOVA Tukey"s multiple compa",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "A Quantification of BRD-1 protein and representative western blot from wild-type worms fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1 Bar graphs are mean ± SEM Data information: Data are presented as mean ± SD N= 8-1 worms per replicate and condition, * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; ### P<0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified",
    "ncbi_link": "frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "B Quantification of mitotic nuclei in single gonad arm of wild-type (WT), brc-1(tm1145) and brd-1(gk297) strains fed as in (A) Data information: Data are presented as mean ± SD N= ), 8-1 worms per replicate and condition, * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; ### P<0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified",
    "ncbi_link": "brc-1: 175499
brd-1: 175959"
  },
  {
    "caption": "Quantification of apoptotic corpse in wild-type (WT), brc-1(tm1145) and brd-1(gk297) strains fed as in (A) and left untreated (C Bar graphs are mean ± SEM. Data information Data are presented a mean ± SEM N= 8-10 worms per replicate and condition, * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; ### P<0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparison",
    "ncbi_link": "brc-1: 175499
brd-1: 175959"
  },
  {
    "caption": "Quantification of apoptotic corpse in wild-type (WT), brc-1(tm1145) and brd-1(gk297) strains fed as in (A) an treated with ionizing radiation 125 Gy (IR) (D). Bar graphs are mean ± SEM. Data information: Data are presented a mean ± SEM N= 8-10 worms per replicate and condition, * P < 0.05, *** P < 0.001 and **** P < 0.0001 vs untreated; ### P<0.001 and #### P < 0.0001 vs con. Not significant if nothing is specified. 2-way ANOVA Tukey"s multiple comparison",
    "ncbi_link": "brc-1: 175499
brd-1: 175959"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type (WT) and, ced-9(n1653ts strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1",
    "ncbi_link": "ced-9: 3565776
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type (WT) an ), brc-1(tm1145) (B strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1",
    "ncbi_link": "brc-1: 175499
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type (WT) an brd-1(gk297) (C strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1",
    "ncbi_link": "brd-1: 175959
frh-1: 174002
isp-1: 177609"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type (WT) an glp-1(e2141) (D strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1",
    "ncbi_link": "frh-1: 174002
glp-1: 176286
isp-1: 177609"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type (WT) an glp4(bn2) (E), strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against frh-1 or isp-1",
    "ncbi_link": "frh-1: 174002
glp4: 173224
isp-1: 177609"
  },
  {
    "caption": "Kaplan-Meier survival curves of wild-type animals fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against isp-1 (F and left untreated or treated with 600, 1200 or 2400 J/m2 UVB",
    "ncbi_link": "isp-1: 177609"
  },
  {
    "caption": "A Kaplan-Meier survival curves of wild-type (WT) and, rrf-1(pk1417), ppw-1(pk2505) strains fed bacteria transformed with either empty-vector (con) or with vector expressing dsRNA against isp-1",
    "ncbi_link": "isp-1: 177609
ppw-1: 172013
rrf-1: 172523"
  },
  {
    "caption": "B Quantification of apoptotic corpses in wild-type (WT) and, rrf-1(pk1417), ppw-1(pk2505) strains fed as (A) and left untreated or treated with 600 J/m2 UVB. Data information: Data are presented as mean ± SEM, N=3, 9-10 worms per replicate and condition ** P < 0.01 vs con; ## P < 0.01 vs WT; ooo P < 0.00 and oooo P < 0.0001 vs untreated . Not significant if nothing is specified. 2-way ANOVA Tukey's multiple comparisons test. C ",
    "ncbi_link": "ppw-1: 172013
rrf-1: 172523"
  },
  {
    "caption": "D. Top: representative Western blots assessing mTOR phosphorylation at S2448 and p70S6K phosphorylation at T389 in PFC of adult 5-HT6-/- mice are illustrated. Bottom: data represent the ratios of immunoreactive signals of the anti phospho-mTOR (S2448) or anti phospho-p70S6K (T389) antibodies to the immunoreactive signal of the anti-β-actin antibody and are expressed in % of values in vehicle-injected 5-HT6-/- mice. They are the means ± S.E.M. of results obtained in four mice per group. n.s. p > 0.05, one-way ANOVA followed by Newman-Keuls test.",
    "ncbi_link": "5-HT6: 15565"
  },
  {
    "caption": "E. Top: schemas illustrating the behavioral tasks in 5-HT6-/- mice. Bottom: the plots represent the discrimination index for the novel object recognition test (discrimination index: 0.30 ± 0.05, N=10 and 0.31 ± 0.03, N=11, for THC+Vehicle and Vehicle+Vehicle conditions, respectively, p > 0.05), the 3-chamber social preference test (sociability index: 0.49 ± 0.04, N=10 and 0.48 ± 0.07, N=11 for THC+Vehicle and Vehicle+Vehicle conditions, respectively, p > 0.05) and the social discrimination test (discrimination index: 0.15 ± 0.06, N=8 and 0.21 ± 0.06, N=8 for THC+Vehicle and Vehicle+Vehicle conditions, respectively, p > 0.05), measured in each condition. One-way ANOVA followed by Bonferroni test (error bars correspond to the mean ± SEM, the dotted line corresponds to a discrimination index equal to zero).",
    "ncbi_link": "5-HT6: 15565"
  },
  {
    "caption": "(B) Flat-mounted retinas from OIR S1pr1f/stop/f and S1pr1 ECTG pups at P17. Blood vessels are stained with isolectin (left) and pathological neovascular tuft area are highlighted in yellow. Avascular area, total and average neovascular tuft areas are quantified (right)",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(C) Flat-mounted retinas from OIR S1pr1f/f and S1pr1 ECKO pups, at P17. Blood vessels are stained with isolectin and neovascular tufts are highlighted in yellow. Avascular area, total and average neovascular tuft areas are quantified.",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(D) Cross sections from OIR S1pr1f/stop/f, S1pr1 ECTG and S1pr1 ECKO P17 pups. Blood vessels are stained with isolectin (red) and nuclei with Hoechst (blue).",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(A) Retinal flat mounts from OIR S1pr1f/stop/f or S1pr1 ECTG or ECKO P17 pups. High-magnification view of neovascular tufts stained for VE-cadherin (green) and Claudin-5 (red). Junctional levels of VE-cadherin and Claudin-5 were quantified as described, for a minimum of 5 animals per genotype.",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(B) Retinal flat mounts from OIR S1pr1f/stop/f or S1pr1 ECTG or ECKO P17 pups. Sites of vascular leakage were assessed by staining for fibrinogen (red), blood vessels are delineated by isolectin (green). Extravascular fibrinogen was quantified as described for a minimum of 5 animals per genotype.",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(D) Flat-mounted retinas from OIR S1pr1f/f and S1pr1 ECKO pups at P21 stained with isolectin. Avascular area, total and average neovascular tuft areas are quantified. A minimum of 7 pups were analyzed per group.",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(A) Flat-mounted retinas from OIR Apom+/- and Apom-/- pups at P17, stained with isolectin. Avascular area, total and average neovascular tuft areas are quantified. (n= 10 pups /group)",
    "ncbi_link": "Apom: 55938"
  },
  {
    "caption": "(B) Flat-mounted retinas from OIR WT and ApomTG pups at P17, stained with isolectin. Avascular area, total and average neovascular tuft areas are quantified. (n= 7 pups /group)",
    "ncbi_link": "Apom: 55937"
  },
  {
    "caption": "(D) Flat-mounted retinas from ApoM-Fc-S1P-treated, OIR S1pr1f/stop/f or S1pr1 ECTG pups at P17, stained with isolectin. Avascular area, total and average neovascular tuft areas are quantified. (n= 6 pups /group)",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(b, c) Immunoblots of recruitment reactions performed as described in (a), with the indicated proteins omitted. In (c), a mid reaction wash in high salt (0.5 M NaCl) buffer (HSW) was included following DDK phosphorylation as indicated.",
    "ncbi_link": "DDK: 851545"
  },
  {
    "caption": "(d) Recruitment reaction performed as in (a), using wild type (wt) or a Cdc45-binding mutant (3E1) of Sld3.",
    "ncbi_link": "Sld3: 852765"
  },
  {
    "caption": "(f) Wild type or mutant FLAG-Sld3 was added to an S-phase protein extract and tested for interaction with Cdc45. Immunoprecipitated proteins were analysed by immunoblot.",
    "ncbi_link": "Sld3: 852765"
  },
  {
    "caption": "(e) Reaction performed as in (a), except Sld3/7 was incubated with Rad53 before addition to reactions. ATP was omitted from this pre-incubation as indicated.",
    "ncbi_link": "Rad53: 855950"
  },
  {
    "caption": "(f) Sld3 recruitment reaction performed as in (a). Sld7 was omitted from this experiment.",
    "ncbi_link": "Sld3: 852765"
  },
  {
    "caption": "(c) Sld3/7 recruitment reaction conducted as in Fig. 2a.",
    "ncbi_link": "Sld3: 852765"
  },
  {
    "caption": "(e) Representative tetrads from dissection of SLD3+/sld3-6E heterozygotes.",
    "ncbi_link": "SLD3: 852765
sld3: 852765"
  },
  {
    "caption": "(b, c, D) Immunoblot of reactions performed as described in (a). In (B), either reconstituted Sld3/7 complex (lanes 6 and 7) or Sld3 alone (lanes 8 and 9) was coupled to beads. In (C), MCM was treated with Lambda Phosphatase after dissociation from DNA (lanes 3 and 7).",
    "ncbi_link": "Sld3: 852765"
  },
  {
    "caption": "(F) Reaction conducted as in (a), using wild type (wt) or the indicated S/T-A substitution mutant versions of Mcm4 and Mcm6. Positions of mutations in Mcm6 are summarised in Fig. EV5c.",
    "ncbi_link": "Mcm4: 856130
Mcm6: 852673"
  },
  {
    "caption": "(b) Replication reaction performed as in Fig. 1g. Experiments in (a) and (b) used MCM containing wild type (wt) or the indicated S/T-A substitution mutant versions of Mcm4 and Mcm6.",
    "ncbi_link": "Mcm4: 856130
Mcm6: 852673"
  },
  {
    "caption": "(d) Representative tetrads from diploids heterozygous for mcm4-25A and mcm6ΔN+11A.",
    "ncbi_link": "mcm4: 856130
mcm6: 852673"
  },
  {
    "caption": "(d) Replication reaction performed as in Fig. 1g. Experiments in (a)-(d) used MCM containing wild type (wt) or S/T-D substitution mutants of Mcm4 and Mcm6 as indicated. In (d), MCM loading was equalised across samples by using 5-fold more mutant than wild type MCM protein, as is shown in Fig. EV6c.",
    "ncbi_link": "Mcm4: 856130
Mcm6: 852673"
  },
  {
    "caption": "E. Osmotic stress does not reduce YAP target gene expression. HEK293A cells were treated with 0.2 M sorbitol for 4 hr. mRNA levels of CTGF and CYR61 were measured by quantitative RT-PCR and normalized to GAPDH control. Data are presented as mean ± SEM. n.s means p > 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "GAPDH: 
CTGF: 1490
CYR61: 3491"
  },
  {
    "caption": "G. Osmotic stress does not increase the interaction between YAP and 14-3-3. HEK293A cells were transiently transfected with Flag-YAP and Myc-14-3-3, then treated with 0.2 M sorbitol for the indicated time points. Myc-14-3-3 was immunoprecipitated and the co-precipitated Flag-YAP was detected.",
    "ncbi_link": "14-3-3: "
  },
  {
    "caption": "B. Osmotic stress induces TAZ nuclear translocation. YAP knockout (KO) HEK293A cells were serum starved for 1 hr followed by 0.2 M sorbitol treatment for 1 hr. TAZ localization was determined by immunofluorescence staining with the YAP/TAZ antibody (red). Scale bar: 20 μm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "D. Osmotic stress induces YAP target gene expression. Wild type (WT) or YAP/TAZ double knockout (Y/T KO) HEK293A cells were serum starved for 1 hr and treated with 0.2 M sorbitol for 4 hr. mRNA levels of CTGF and CYR61 were measured by quantitative RT-PCR and normalized to GAPDH control. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "GAPDH: 
CTGF: 1490
CYR61: 3491
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "E. Osmotic stress decreases YAP and 14-3-3 interaction. HEK293A cells were transiently transfected with Flag-YAP and Myc-14-3-3, and were serum starved for 16 hr. Cells were then treated with 0.2 M sorbitol for the indicated time points. Myc-14-3-3 was immunoprecipitated and the associated Flag-YAP was detected by Western. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "14-3-3: "
  },
  {
    "caption": "B. NLK knockout blocks osmotic stress-induced YAP nuclear localization. HEK293A cells were transiently transfected with CRISPR/Cas9 to knockout NLK. Wild type (WT) cells and the NLK KO cell pool were treated with 0.2 M sorbitol for 1 hr in the absence of serum. YAP/TAZ subcellular localization was determined by immunofluorescence staining. Scale bar: 20 μm.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "C. NLK induces YAP nuclear translocation. HEK293A cells were co-transfected with Flag-YAP together with vector control, Myc-NLK-WT (wild type NLK), or NLK-KN (kinase negative mutant). Cells were serum starved for 6 hr, and YAP localization and NLK expression were determined by Flag (green) and Myc (red) antibodies, respectively. Scale bar: 20 μm.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "D. NLK induces YAP phosphorylation. HA-YAP was co-transfected with NLK-WT or NLK-KN in HEK293A cells. The phos-tag gel showed NLK-WT but not NLK-KN caused a significant mobility shift of YAP.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "E. NLK phosphorylates YAP in vitro. NLK-WT and NLK-KN were immunoprecipitated from HEK293A cells and an in vitro kinase assay was performed using recombinant GST-YAP as a substrate in the presence of ATP-γ-S. Total phosphorylation of YAP was detected by immunoblotting with thiophosphate ester antibody, which identifies the alkylated thiophosphorylation on YAP.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "A. NLK induces YAP Ser 128 phosphorylation. Flag-YAP WT or S128A mutant was co-transfected with or without Myc-NLK. Phosphorylation was determined by Western blot using YAP S128 phosphospecific antibody.",
    "ncbi_link": "NLK: 51701
YAP: 10413"
  },
  {
    "caption": "B. NLK phosphorylates YAP Ser 128 in vitro. NLK-WT or NLK-KN was transfected into HEK293A cells and immunoprecipitated. An in vitro NLK kinase assay was performed using recombinant GST-YAP as a substrate. Phosphorylation of YAP Ser 128 was determined by immunoblotting with phospho-YAP (S128) antibody.",
    "ncbi_link": "NLK: 51701
YAP: 10413"
  },
  {
    "caption": "D. NLK deficiency reduces YAP S128 phosphorylation. Two CRISPR/CAS9 gRNA plasmids targeting different sites of NLK were transfected into HEK293A. WT cells and two pools of NLK CRISPR/CAS9 transfected cells were treated with 0.2 M sorbitol for the indicated time points. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 4).",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "E. The S128D phosphomimetic mutant abolishes YAP interaction with 14-3-3. Flag-YAP WT and mutant constructs were co-transfected with Myc-14-3-3 into HEK293A cells. Cells were serum starved for 16 hrs. 14-3-3 was immunoprecipitated with Myc antibody and the associated YAP was detected with Flag antibody.",
    "ncbi_link": "14-3-3: 
YAP: 10413"
  },
  {
    "caption": "F. YAP Ser 128 phosphorylation is required for disruption of YAP-14-3-3 interaction by osmotic stress. Flag-YAP WT or Flag-YAP S128A constructs were co-transfected with Myc-14-3-3 into HEK293A cells. Cells were serum starved for 16 hrs, and treated with 0.2 M sorbitol for the indicated time points or refreshed with serum containing medium for 1 hr. Refreshing medium served as a control to disrupt YAP and 14-3-3 binding.14-3-3 was immunoprecipitated with Myc antibody, and the associated YAP was detected with Flag antibody. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "14-3-3: 
YAP: 10413"
  },
  {
    "caption": "A. NLK does not induce nuclear translocation of the S128A mutant YAP. HEK293A cells were co-transfected with Myc-NLK and Flag-YAP WT or S128A mutant. Cells were serum starved for 6 hr, and YAP localization and NLK expression were determined by Flag (green) and Myc (red) antibodies, respectively. Scale bar: 20 μm.",
    "ncbi_link": "NLK: 51701
YAP: 10413"
  },
  {
    "caption": "B. YAP Ser 128 phosphorylation is required for osmotic stress-induced YAP nuclear localization. HEK293A YAP KO cells reconstituted with Flag-YAP WT, YAP S128D, or YAP S128A mutant were treated with 0.2 M sorbitol for 1 hr. YAP subcellular localization was determined by Flag immunofluorescence staining (green). Scale bar: 20 μm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "A. YAP S128D reconstituted cells show growth advantage under hyperosmotic conditions. YAP/TAZ dKO HEK293A cells with stable expression of YAP WT, S128A, and S128D were cultured in the absence (left panel) or presence of 0.2M sorbitol (right panel) for the indicated amount of time. Cell numbers were counted and normalized to day 0. Data are presented as mean ± SEM, n = 3.",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "B. YAP S128D reconstituted cells have lower cell death in a hyperosmotic environment. Cell cycle analyses of YAP/TAZ dKO HEK293A cells with stable expression of YAP WT, S128A, and S128D after 0.2 M sorbitol treatment were determined using flow cytometry. Propidium iodine (PI) was used for DNA staining (Fig EV5). Quantification of sub-G1 cells is shown. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "C. YAP S128D reconstituted cells show reduced apoptosis under hyperosmotic conditions. Annexin V analyses of YAP/TAZ dKO HEK293A cells with stable expression of YAP WT, S128A, and S128D after 0.2 M sorbitol treatment were determined using flow cytometry. PE-Annexin V and 7-AAD stained for phospholipid phosphatidylserine (PS) and DNA, respectively. Data are presented as mean ± SEM. *p < 0.05 (two tailed student's t-test, n = 3).",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "B Wildtype (Ocrl+/y) and Ocrl-/- MEF cells were grown in  complete media or 5 h  serum starvation, then immunostained with indicated antibodies. Dashed lines in images outline cell boundaries. Scale bar, 10 μm.",
    "ncbi_link": "Ocrl: 320634"
  },
  {
    "caption": "I Snap  images of WT (Ocrl+/y), OCRL knockout (Ocrl-/-) and  IOB MEFs transfected  with lysosome-GFP. After transfection, WT, OCRL knockout and IOB MEFs were left in serum starvation  for 8 h. Scale bar, 5 μm. J Quantitative analyses of tubulated lysosomes in the experiments shown in H. n = 3 per group in which 10 cells were counted per condition per experiment. D Data information: data are presented as mean ± SEM. * ≤ 0.05, ** ≤ 0.01, ***≤ 0.001, ****P ≤ 0.0001, n.s., not significant, calculated by two-tailed Student's t-test.",
    "ncbi_link": "Ocrl: 320634
OCRL: 320634"
  },
  {
    "caption": "A Immunoblot analysis of endogenous p-mTOR (Ser2448), total mTOR, p-p70 S6K (Thr389) and total p70 S6K in NHF, Lowe 1676 and Lowe 3265 cells grown in complete media or 5 h serum starvation. p-p70 S6K (Thr389) over total p70 S6K ratios normalized to NHF cells, three independent experiments. B Immunoblot analysis of endogenous p-mTOR (Ser2448), total mTOR , p-p70 S6K (Thr389) and total p70 S6K in WT (Ocrl+/y) and IOB MEFs grown in complete medium or 5 h serum starvation. p-p70 S6K (Thr389) over total p70 S6K ratios normalized to NHF  cells, three independent experiments. C Data information: data are presented as mean ± SEM. * ≤ 0.05, ** ≤ 0.01, ***≤ 0.001, ****P ≤ 0.0001, n.s., not significant, calculated by two-tailed Student's t-test unless otherwise stated.",
    "ncbi_link": "Ocrl: 320634"
  },
  {
    "caption": "C WT (Ocrl+/y), OCRL knockout (Ocrl-/-) and IOB MEFs derived from the corresponding mice were  costained with anti-α-tubulin and anti- γ-tubulin antibodies.  Nuclei were stained with DAPI (blue). Scale bar, 10 μm. D Quantitative analyses of focused microtubule arrays  numbers at  γ-tubulin (microtubule organizing center MTOC) measured in the experiments shown in C. n = 3 per group in which 30 cells were counted per condition per experiment. E Data information: data are presented as mean ± SEM. * ≤ 0.05, ** ≤ 0.01, calculated by two-way ANOVA, multiple comparisons.",
    "ncbi_link": "Ocrl: 320634
OCRL: 320634"
  },
  {
    "caption": "H Representative  images of the co-localization of OCRL-WT, GFP-OCRL-△RhoGAP and GFP-OCRL-△ASH+RhoGAP with γ-tubulin. Insets, enlargements of the outlined areas. Scale bars, 10 μm. I Quantitative analysis of cells with and without centrosomal OCRL (centrosomal GFP signal) in the experiments shown in A. n = 3 per group in which 10 cells were counted per condition per experiment. Means ±SEM, ****P < 0.0001, n.s., not significant, calculated by two-way ANOVA, multiple comparisons. ",
    "ncbi_link": "OCRL: 4952"
  },
  {
    "caption": "A RPE-1 cells transfected with nontargeting control siRNA or OCRL siRNA, were left for 48 h, then subjected to IF microscopy to visualize PI(4,5)P2 (green), γ-tubulin (red) and nuclei  (blue, DAPI staining). Scale bar, 10 μm. B Quantitative analyses of centrosomal PI(4,5)P2 fluorescence intensity in the experiments shown in A. n = 3 per group in which 50 cells were counted per condition per experiment. C Data information: data are presented as mean ± SEM. n.s., not significant, calculated by calculated by two-tailed Student's t-test.",
    "ncbi_link": "OCRL: 4952"
  },
  {
    "caption": "A SSX2IP interacts with  OCRL. Plasmids carrying GFP-OCRL-WT, GFP-OCRL-△RhoGAP and GFP-OCRL-△ASH+RhoGAP  were transfected into RPE-1  cells. Immunoprecipitation was performed with GFP-Trap, followed by blotting with the indicated antibodies.",
    "ncbi_link": "GFP: 
RhoGAP: 392
ASH: 2885
OCRL: 4952"
  },
  {
    "caption": "D NHF, Lowe 1676 and  Lowe 3265 cells were transfected with wildtype GFP-SSX2IP  or GFP-PACT-SSX2IP for 48 h, then immunostained with anti-β-tubulin (red) antibody. Nuclei (blue) were  stained with DAPI. The centrosomal microtubule nucleation in  GFP-PACT-SSX2IP transfected cells was indicated by white arrowhead. Scale bar, 5 μm.",
    "ncbi_link": "GFP: 
PACT: 
SSX2IP: 117178"
  },
  {
    "caption": "F Western blot analysis of GFP, endogenous phospho-mTOR, total  mTOR, in NHF and Lowe 1676 cells. NHF and Lowe 1676  cells were left untransfected, transfected with GFP-SSX2IP-WT or GFP-PACT-SSX2IP, then immunoblotted with indicated antibodies.",
    "ncbi_link": "GFP: 
PACT: 
SSX2IP: 117178"
  },
  {
    "caption": "(b) Immunofluorescence for LC3 and Atg16 in normal rat kidney (NRK) cells expressing GFP-Cx43 maintained in the presence or absence of serum for 4 h. Single channels are shown in reverse black and white, and magnification of single and merged images are shown in colour. Arrows: co-localization of Atg16/Cx43 (yellow) or Atg16/Cx43/LC3 (white). Quantification is shown in Supplementary Fig. 1c.",
    "ncbi_link": "Cx43: 24392"
  },
  {
    "caption": "(e) Immunofluorescence for LC3 and Atg16 in NRK cells expressing GFP-Cx43 but knocked down for Eps15. Single channels are shown in reverse black and white, and merged images in colour. Inset shows higher magnification. Bottom: Quantification of co-localization between Atg16 and Cx43 (n = 3 wells, 4 independent experiments, >20 cells per experiment). Values are mean + s.e.m. * P 0.05.",
    "ncbi_link": "Eps15: 313474
Cx43: 24392"
  },
  {
    "caption": "(h) Immunoblot for the indicated proteins of immunoprecipitates (IP) of endogenous Cx43 from untreated WT MEFs, on incubation with 3-methyladenine (3MA) or in MEFs from Atg5-null mice (Atg5−/−).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(i) Immunoblot for Flag and Cx43 of immunoprecipitates (IP) of endogenous Cx43 in WT MEFs transfected with the indicated Flag-tagged constructs of truncated Atg16.",
    "ncbi_link": "Atg16: 73683///77040"
  },
  {
    "caption": "(a) Immunostaining for LC3 and GABARAP in MOBs from WT or Cx43-null mice (Cx43−/−) grown in serum-supplemented media. Reverse black and white channels (top) and colour images (bottom). Right: Average number of LC3 and GABARAP puncta per cell (n = 3 wells, 3 independent experiments, >50 cells per experiment).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(b) Electron micrographs of WT and Cx43−/− MOBs grown in serum-supplemented media. Yellow arrows: autophagic vacuoles. Insets: autophagic vacuoles (AV) at higher magnification. Right: Percentage of cytoplasm area occupied by AV (top) and number of AV per area (bottom; n = 3 mice, >10 micrographs per mice).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(e) Electron micrographs of livers from WT and Cx43+/− mice. Arrows indicate AV. Right: Percentage of cytosolic area occupied by AVs (n = 3 mice, >10 micrographs per mice).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(f) Immunofluorescence for LC3 in Cx43−/− MOBs expressing GFP-tagged full-length Cx43. Single channels (inverted black and white) and merged channels (colour). Asterisks: transfected (green) and untransfected (red) cells. (g) LC3-positive puncta per cell in the indicated cells (n = 3 wells, 3 independent experiments, >50 cells per experiment). All values are mean + s.e.m. and differences from WT were significant for *P 0.01. Nuclei are highlighted with DAPI. Scale bars: 5 μm in fluorescence images; 1 μm and 0.1 μm in top panels and insets of b and e. Uncropped images of blots are shown in Supplementary Fig. 9.",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(a) Immunoblot for LC3 in MOBs from WT or Cx43-null mice (Cx43−/−) treated with vehicle or with 18α glycyrrhetinic acid (18α GA). Glyceraldehyde-3-dehydrogenae (GPD) is shown as the loading control. Levels of LC3-II (left) and LC3-II flux (right; n = 3 independent experiments).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(c) Immunofluorescence for LC3 in WT or Cx43−/− MOBs treated with the indicated kinase inhibitors for 2 h. Insets: Higher magnification images in inverted black and white. (d) Endogenous LC3 puncta in the same cells shown in c (n = 3 wells, 3 independent experiments, >50 cells per experiment). *, differences from WT; §, differences from untreated.",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(e) LC3 puncta in Cx43−/− MOBs transfected with constructs coding for different forms of Cx43 (full length, CT, ΔCT258 or ΔCT245) tagged as indicated in the scheme. Left: Representative images. Merged fields (left) and LC3 channel in reverse black and white (right) are shown (images of GFP-Cx43 are shown in Fig. 2f). Right: Quantification of the average number of LC3 puncta per cell (n = 3 wells, 3 independent experiments, >50 cells per experiment).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(f,g) Immunoblot for the indicated proteins of the immunoprecipitates (IP) of Atg16 from MEFs transfected with GFP-tagged full-length (FL-) Cx43 or Flag-tagged C terminus (CT-) Cx43 (f) or ΔCT258-Cx43 (g) I: input; FT: flow through. GAPDH and GFP alone were used as negative controls for immunoprecipitation and Atg5 as the positive control. All values are mean + s.e.m. Differences from the control were significant for (*, §)P 0.01 and (**, §§)P 0.001. Scale bars: 5 μm. Uncropped images of blots are shown in Supplementary Fig. 9.",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(d) Fluorescence images of WT or Cx43−/− MOBs transfected with mCherry-GFP-LC3 and incubated or not with tamoxifen or lindane. Bottom: Quantification of autophagolysosomes (n = 3 wells, 3 independent experiments, >50 cells per experiment).",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(g,h) Immunostaining for Atg16 in Cx43 knocked down (KD) (g) or knocked out (−/−) (h) cells. Right: quantification of the average of cytosolic Atg16 positive puncta per cell (n = 3 wells, 3 independent experiments, >50 cells per experiment).",
    "ncbi_link": "Cx43: 24392"
  },
  {
    "caption": "(c) Immunoblot of Cx43 IP in MEFs from WT or Atg5−/− mice grown in serum-supplemented media.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(d) Immunoblot of Cx43 IP in WT or Atg16 knockdown (KD) MEFs maintained in the presence/absence of serum for 4 h.",
    "ncbi_link": "Atg16: 73683///77040"
  },
  {
    "caption": "(g) Immunoblot of Atg14 IP in WT or Atg5−/− MEFs maintained in the presence of serum.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(h) Immunoblot in total homogenates and PM purified from WT or Cx43−/− MOBs.",
    "ncbi_link": "Cx43: 14609"
  },
  {
    "caption": "(i) Immunofluorescence for e-cadherin and Vps34 in NRK cells WT or knocked down (KD) for Cx43. Single channel and merge (left) and z-stack surface reconstruction and higher magnification of the outlined region (right).",
    "ncbi_link": "Cx43: 24392"
  },
  {
    "caption": "(d) Co-staining for Atg9 and e-cadherin in control NRK cells and those knocked down for Cx43. Single and merged channels at higher magnification areas are shown.",
    "ncbi_link": "Cx43: 24392"
  },
  {
    "caption": "(e) Immunofluorescence for endogenous Atg9 and Cx43 in control NRK cells and those knocked down for Eps15.",
    "ncbi_link": "Eps15: 313474"
  },
  {
    "caption": "(f,g) Immunofluorescence for endogenous Cx43 (green) in control NRK cells or those knocked down for Atg14 (f) maintained in the presence or absence of serum.",
    "ncbi_link": "Atg14: 305831"
  },
  {
    "caption": "(f,g) Immunofluorescence for endogenous Cx43 (green) in control NRK cells or those knocked down for Atg9 (g) maintained in the presence or absence of serum. E-cadherin staining (red) is shown to highlight PM in g and h.",
    "ncbi_link": "Atg9: 499973///363254"
  },
  {
    "caption": "(h) Immunofluorescence of endogenous Cx43 in control NRK cells or those knocked down for Atg14, treated (or not) with tamoxifen or lindane (left). E-cadherin staining (red) is shown to highlight PM in g and h. Full fields are shown in Supplementary Fig. 6h. Quantification of intracytoplasmic Cx43-positives vesicles (right; n = 3 wells, 3 independent experiments, >30 cells per experiment). Values are mean + s.e.m and significant for *P 0.01 and **P 0.001 using analysis of variance + Bonferroni test. Scale bars: 5 μm. Uncropped images of blots are shown in Supplementary Fig. 9.",
    "ncbi_link": "Atg14: 305831"
  },
  {
    "caption": "A. Total cell lysates from wild type (WT) and HAT1  knockout (KO) Clone 1 HepG2 cells were analyzed for the levels of Ksucc and Kac  by   Western blot analysis (left). The expression levels of  HAT1, Histone H3 (H3), and beta-actin (β-actin) were measured by Western blot analysis in the cells (right).",
    "ncbi_link": "HAT1: 8520"
  },
  {
    "caption": "A. The levels of histone H3K122 succinylation, histone H3K122 acetylation, histone H3K27 acetylation, histone H3, HAT1, and β-actin were examined by Western blot analysis in HepG2, HAT1 knockout (KO) Clone 1 HepG2 cells, and in HAT1 KO cells reconstituted with either HAT1 or mutant HAT1 (T188A).",
    "ncbi_link": "HAT1: 8520"
  },
  {
    "caption": "D. The effect of HAT1 on histone H3K122 succinylation and histone H3K122 acetylation at the indicated gene promoters was determined by ChIP assays with anti-H3K122 succinylation antibody and anti-H3K122 acetylation antibody, and followed by quantitative PCR with primers of the promoter regions of CREBBP, BPTF and RPTOR  in WT HepG2 cells, HAT1  KO HepG2  cells and HAT1 KO HepG2  cells reconstituted with either wildtype HAT1 or mutant HAT1 (T188A). N = 3 biological replicates. Data were presented as mean ± SD. Student's t-test, ***P < 0.001; ns, no significance.",
    "ncbi_link": "BPTF: 2186
CREBBP: 1387
HAT1: 8520
RPTOR: 57521"
  },
  {
    "caption": "B. Bar graphs depicting the relative ratio of succinylation in HAT1 KO versus WT of the 7 key enzymes in the glycolysis pathway depicted in (A). N = 3 biological replicates. Data were presented as mean ± SD.",
    "ncbi_link": "HAT1: 8520"
  },
  {
    "caption": "F. The decrease of glucose  and increase of lactate in the culture medium and the relative amounts of  2-PG and 3-PG were analyzed by ELISA  assays in HepG2 cells depleted endogenous PGAM1 and reconstituted expression of PGAM1 or PGAM1  mutant (K99R). N = 3 biological replicates. Data are presented as mean ± SD. Student's t-test, **P < 0.01.",
    "ncbi_link": "PGAM1: 5223"
  },
  {
    "caption": "B. The effect of  HAT1-mediated succinylation on cancer  cell  proliferation  was measured by  MTS assays in the indicated cells. N = 3 biological replicates. Data are presented as mean ± SD. Student's t-test, **P < 0.01. C. The effect of PGAM1 succinylation on cancer cell proliferation was measured by MTS assays in the indicated cells. N = 3 biological replicates. Data are presented as mean ± SD. Student's t-test, **P < 0.01. ",
    "ncbi_link": "HAT1: 8520
PGAM1: 5223"
  },
  {
    "caption": "HepG2 cells,  HAT1 KO  HepG2 cells, and HAT1 KO HepG2 cells reconstituted with either wild type HAT1 or mutant HAT1 (T188A) were subcutaneously injected into athymic nude mice Tumor volumes and average tumor weight were calculated. N = 6 biological replicates. Scale bar = 10 mm. In the boxplots, boxes extend from the 25th to 75th percentiles (inter‐quartile range (IQR)), central band represents the median, whiskers indicate the lowest and highest data within 1.5 × IQR from the lower and upper quartiles, respectively. Student's t-test, ***P < 0.001",
    "ncbi_link": "HAT1: 8520"
  },
  {
    "caption": "B Expression of PDI variants in zebrafish. Zebrafish embryos at 1-2 cell stage were injected with sense mRNA coding for the indicated PDIs (PDIA1WT, PDIA1D292N and PDIA1R300H: 200 pg/embryo; ERp57WT, ERp57D217N and ERp57Q481K: 80 pg/embryo). Protein expression was confirmed by Western blot analysis using anti-V5 antibody in total embryo extracts at 24 h post-fertilization (hpf). Actin was used as a loading control. In the left panel 80 µg protein and in the right panel 120 µg protein extract were used.",
    "ncbi_link": "PDIA1: 5034
ERp57: 2923"
  },
  {
    "caption": "C and D, Motoneuron defects induced in zebrafish embryos after expression of the indicated ALS-linked PDI mutants and wild-type controls (PDIA1WT and PDIA1R300H: 80 pg mRNA/embryo; ERp57WT, ERp57D217N, ERp57D217N and ERp57Q481K: 30 pgtba mRNA/embryo). The most frequent global phenotypes induced by PDI injection are shown in lateral views of embryos at 24 hpf (left column). Black arrows indicate the presence of curly tail and/or shorter axis phenotypes (see details in Appendix Table S1). Axon motoneuron morphology was visualized using confocal microscopy in lateral views of the trunk region in transgenic Tg(Huc:Kaede) zebrafish at 36 hpf (middle and right columns). Images in the right column correspond to magnification views of the rectangular regions depicted in left and middle columns. Asterisks and arrows point to examples of increased axonal branching and reduced axonal length, respectively.",
    "ncbi_link": "PDIA1: 5034
ERp57: 2923"
  },
  {
    "caption": "C and D, Motoneuron defects induced in zebrafishembryos after expression of the indicated ALS-linked PDI mutants and wild-type controls (PDIA1WT and PDIA1R300H: 80 pg mRNA/embryo; ERp57WT, ERp57D217N, ERp57D217N and ERp57Q481K: 30 pgtba mRNA/embryo). The most frequent global phenotypes induced by PDI injection are shown in lateral views of embryos at 24 hpf (left column). Black arrows indicate the presence of curly tail and/or shorter axis phenotypes (see details in Appendix Table S1). Axonmotoneuronmorphology was visualized using confocalmicroscopy in lateral views of the trunk region in transgenic Tg(Huc:Kaede) zebrafish at 36 hpf (middle and right columns). Images in the right column correspond to magnification views of the rectangular regions depicted in left and middle columns. Asterisks and arrows point to examples of increased axonal branching and reduced axonal length, respectively.",
    "ncbi_link": "PDIA1: 5034
ERp57: 2923"
  },
  {
    "caption": "E and F Quantification of motoneuron axon length and axon branching in 36hpf Tg(Huc:Kaede) embryos injected with the indicated PDIA1 (D) and ERp57 (E) mutants.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "E and F Quantification of motoneuron axon length and axon branching in 36hpf Tg(Huc:Kaede) embryos injected with the indicated PDIA1 (D) and ERp57 (E) mutants.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "A NSC34cells were transiently transfected with expression vectors for V5-tagged wild-type and mutant PDIs. After 48 h, overexpressed PDI variants was assessed under reducing conditions in an 8% SDS-PAGE. An antibody detecting total PDIA1 (endogenous mousePDIA1 and exogenous humanV5-tagged PDIA1) (first panel). A second antibody detects only humanPDIA1, therefore only V5-tagged PDIA1 appears (second panel). A mouse and human specific antibody was used to detect total ERp57 (third panel). Anti-V5 was used to detect the exogenous PDI variants. Anti-β-actin was used as a loading control.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "E Human motoneurons were differentiated from the human embryonic stem cell (ESC) HuESC 3 Hb9::GFP line. Differentiated neurons were transduced with lentivirus expressing GFP alone or together with PDIs-expressing plasmids. Transduced cells were cultured for another 10 days. To identify motoneurons after lentiviral transduction, immunocytochemistry analyses were performed. Quantification of neurite outgrowth in the different experimental conditions of GFP and HB9 positive neurons were obtained. Neurite number and assessment of the length of each neurite was performed in a similar manner as for primary rat motoneurons (see methods). Four independent experiments were performed.",
    "ncbi_link": "Hb9: 3110"
  },
  {
    "caption": "F NSC34 cell lines stably knocked down for PDIA1 or ERp57 were differentiated for 24 h in Neurobasal medium containing B27 supplement to induce cell differentiation. The percentage of cells with neurites was quantified in the three independent experiments. A minimum of 100 cells per experiment was analyzed.Statistical analyses were performed using one-way ANOVA and Bonferroni´s post hoc tests. Mean ± SEM with only statistically significant p values are shown: *, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001.",
    "ncbi_link": "PDIA1: 18453
ERp57: 14827"
  },
  {
    "caption": "A PDI mutants form abnormal disulfide-dependent protein complexes. NSC34 cells were transiently transfected with expression vectors for V5-tagged wild-type and mutant PDIA1. After 48 h, differential disulfide-dependent interactions/aggregations of overexpressed PDI variants was assessed under reducing (+DTT) and non-reducing (-DTT) conditions in an 8% SDS-PAGE. Anti-V5 was used for detection in Western blot.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "B Analysis of the PDIA1 structure to model the effects of the R300H mutation. The close association between Arg300 located to the b' domain of PDIA1 with Trp396 located to the a' domain adjacent to the active site motif CGHC (designated as AS in yellow) is shown in comparison to the mutated version of PDIA1R300H highlighting the same residues. A potential stabilization of the interaction between the b' and a' domain is shown that may be caused by the interaction of the imidazole rings of mutated His300 with Trp396.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "C ALS-linked PDIA1 variants were generated as recombinant proteins and then analyzed by circular dichroism (CD). Averages for CD spectroscopic scans of PDIA1WT and mutants are shown.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "D Averages for CD spectroscopic thermal denaturation of recombinant PDIA1WT and mutants.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "E Representative electrophoresis analysis of Proteinase K-treated recombinant PDIA1 variants. Mass spectrometric analysis of Proteinase K digested samples from total sample and from in gel trypsin digested protein samples (arrows indicate band 1 and band 2) indicated differences in the removal of the x-linker region. Bottom panel: Ratios of band 1 to band 2 were quantified in 4 independent experiments.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "F Representative fluorescence spectra of recombinant PDIA1b'xWT fragments and the equivalent ALS-linked mutants (n=6). Ratios from the two peak areas and change compared to PDIA1 b'xWT. Both mutants analyzed show a significant shift in peak position compared to wild-type, but in opposite directions, suggesting that PDIA1D292N shifts equilibrium towards the capped version (x region over the binding pocket) and the PDIA1R300H mutant towards the uncapped version (Nguyen et al, 2008).",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "G The activity of recombinant PDIA1 was measured in vitro using a BPTI refolding assay following by mass spectrometry analysis. The percentages of different BPTI species was calculated (6H, fully reduced; 1S, one disulfide bond; 2S, two disulfide bonds; 3S, three disulfide bonds) at time point 2.5 min in four independent experiments.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "I HEK293T cells were transfected with expression vectors for V5-tagged wild-type and mutant PDIA1, as well as empty vector. After 48 h, V5-tagged proteins were immunoprecipitated and eluted with V5 peptide. The interaction with endogenous ERO1Lα was analyzed by western blot. The inputs and elutions are shown as control. Right panel: Quantification of the degree of interaction is presented.",
    "ncbi_link": "PDIA1: 5034"
  },
  {
    "caption": "A PDI mutants form abnormal disulfide-dependent protein complexes. NSC34 cells were transiently transfected with expression vectors for V5-tagged wild-type and mutant ERp57. After 48 h, differential disulfide-dependent interactions/aggregations of overexpressed PDI variants was assessed under reducing (+DTT) and non-reducing (-DTT) conditions in an 8% SDS-PAGE. Anti-V5 was used for detection in Western blot.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "B ALS-linked ERp57 variants were generated as recombinant proteins and then analyzed by circular dichroism (CD). Averages for CD spectroscopic scans of recombinant ERp57WT and mutants are shown.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "C A thermal denaturation curve of ERp57WT and mutants was performed.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "D Representative electrophoresis of Proteinase K treated ERp57 recombinant proteins.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "E Surface Plasmon Resonance was performed to monitor the affinity of recombinant ERp57 for recombinant CRT P-domain. KD values are expressed as percentage of ERp57WT. Values are derived from four independent experiments. For absolute KD values please see Appendix Table S2.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "FHEK293T NSC34 were transfected with expression vectors for V5-tagged wild-type and mutant ERp57, as well as empty vector. After 48 h, V5-tagged proteins were immunoprecipitated and eluted with V5 peptide. The interaction with endogenous calnexin (CNX) and calreticulin (CRT) was analyzed by Western blot. The inputs and elutions are shown. Right panel: Quantification of the degree of interaction is presented.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "G The gain of an N-glycosylation site of ERp57D217N was predicted after the analysis of the protein sequence since the change of Asp217 to an Asn creates the NXT/S consensus sequence. Neuro2a cells were transfected with expression vectors for V5-tagged wild-type and mutant ERp57, as well as empty vector and treated with 1 µg/ml tunicamycin (Tm) for 20 h to inhibit N-glycosylation. Alternatively, protein extracts were digested with PNGase F and the possible removal of the N-glycosylation was analyzed by Western blot using anti-V5 antibody.",
    "ncbi_link": "ERp57: 2923"
  },
  {
    "caption": "A ERp57flox/flox mice were crossed with Nestin Cre transgenic mice to generate nervous system specific ERp57 deficient animals. The levels of ERp57 protein in the spinal cord were monitored by Western blot. ERp57WT (n=4), ERp57Nes+/- (n=5) and ERp57Nes-/- (n=4) mice. HSP90 levels were determined as a loading control. Right panel: Quantification of ERp57 levels was performed relative to Hsp90 levels.",
    "ncbi_link": "Cre: 
Nestin: 
ERp57: 14827"
  },
  {
    "caption": "B Body weight measurements were performed for indicated time points in ERp57WT (n=50), ERp57Nes+/- (n=32) and ERp57Nes-/- (n=19) mice.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "C Rotarod performance was performed ERp57WT (n=20), ERp57Nes+/- (n=15) and ERp57Nes-/- (n=8) mice.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "D Hanging test performance was assessed in ERp57WT (n=41), ERp57Nes+/- (n=32) and ERp57Nes-/- (n=12) mice.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "E Kaplan-Meier survival curve for ERp57Nes-/- mice (N = 19) that prematurely died or had to be sacrificed because of health reasons between the ages 22 and 73 days. Mean survival of this subgroup of animals was 57 days. ERp57WT (n=50) and ERp57Nes+/- (n=32) mice are shown as a reference.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "F Histological analysis of NeuN and GFAP staining was performed in spinal cord tissue from ERp57WT and ERp57Nes-/- mice in three animals per group using indirect immunofluorescence. The nucleus was stained with Hoechst. Representative images from one mouse per group are shown. Scale bar: 50 μm.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "G Stereological analysis of the spinal cord from ERp57WT (n = 4), ERp57Nes+/- (n = 4) and ERp57Nes-/- (n = 4) mice. Alternate series of sections from the spinal cord of the mice were either stained for Nissl (top row images) or processed for immunohistochemistry for the cholinergic cell marker Choline Acetyl Transferase (ChAT, bottom row images). The nucleoli of the motoneurons, as stained in the Nissl series, were counted inside the motoneurons pools previously defined using the adjacent ChAT series (contours not shown). Cell densities of the three genotypes are shown on the right plots. No significant differences were found between the genotypes. Scale bar represents 200 μm and 50 μm on large and inset images, respectively.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "H Representative images of the spinal cord myelination of ERp57WT and ERp57Nes-/- mice.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "A Representative EMG recordings of ERp57WT (n=16), ERp57Nes-/+ (n=12) and ERp57Nes-/- (n=5) mice is presented. The presence of positive sharp waves (PSW) in ERp57Nes+/- and ERp57Nes-/- mice indicated muscle denervation.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "B Analysis of NMJ and muscle morphologies were performed from ERp57WT (n=5), ERp57Nes+/- (n=5) and ERp57Nes-/- (n=4). Quantifications of endplate width, measuring the most ventral region of the diaphragms every 134 µm considering both sides of the innervation profile. Twenty to forty measurements per diaphragm were obtained per animal.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "C Whole-mounted diaphragms from ERp57WT and ERp57Nes-/- mice were co-stained with anti-neurofilament (red) and α-BTX to reveal the postsynaptic densities (green). 3D reconstructions (lower panel) of higher magnification. ERp57WT NMJs are fully innervated pretzel-like, whereas ERp57Nes-/- NMJs display less complex postsynaptic densities and an incomplete or aberrantly distributed innervation pattern (Movies EV4-7).",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "A The levels of ERp57 protein in the muscle were monitored by Western blot. ERp57WT (n = 4), ERp57Nes+/- (n = 5) and ERp57Nes-/- (n = 4) mice. HSP90 was determined as loading control.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "B Tibialis anterior muscles from ERp57WT (n = 5), ERp57Nes+/- (n = 5), and ERp57Nes-/- (n = 4) mice were dissected and cryosectioned (20 µm) for the analysis of several parameters of muscle physiology. Upper panel: hyaluronic acid (HA) staining was performed to assess the gross morphology of the muscle. Middle panel: Bismarck brown staining to monitor skeletal muscles fibrosis. Lower panel: Cryosections were then double stained with wheat germ agglutinin (WGA) to visualize plasmamembrane and nuclei. The absence of central nuclei in all genotypes suggests that ERp57 deficiency does not affect degeneration/regeneration cycles. Images are representative of each genotype and where acquired in the same anatomical region of the TA muscles.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "C Tibialis anterior cryosections (20 µm) from ERp57WT, ERp57Nes+/-, and ERp57Nes-/- mice were stained for NADH-TR activity to identify oxidative myofibers (upper panel). Representative micrographs of transversal cryosections show variable proportions of light, intermediate and dark positive staining in the different genotypes: (middle panel) NADH-TR positive (slow-twitch) and negative (fast-twitch) myofibers were quantified as percentage of total for every genotype (lower panel) The mean diameter of slow- and fast-twitch muscle fibers was evaluated at the light microscope using the ImageJ software. Data represent the average ± SEM of >300 fibers per animal.Scale bars represent 50 m in B and C.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "A The levels of synaptic proteins SV2, NMDAR2A, PSD95 and Synaptophysin in the cortex were monitored by Western blot. ERp57WT (n = 4), ERp57Nes+/- (n = 5) and ERp57Nes-/- (n = 4) mice. HSP90 and β-Actin were determined as loading controls.",
    "ncbi_link": "ERp57: 14827"
  },
  {
    "caption": "In  MM.1S  cells treated with mycolactone  and/or BZ  at the indicated concentrations, or vehicle as control for 6 h: (D) CHOP  and GADD34 mRNA levels were quantified by  qPCR Data information: Shown mRNA data are Mean fold changes (2-∆∆CT) ± SD, relative to untreated controls (cumulative data of at least 2 independent experiments with technical duplicates or triplicates), pairwise compared by nested one-Way ANOVA with Tukey's multiple comparison test, exact p-values indicated.  Thapsigargin (Tg, 2 µM, 6 h), Tunicamycin (Tu, 2 µM, 6 h) were used as positive controls.",
    "ncbi_link": "CHOP: 1649
GADD34: 23645"
  },
  {
    "caption": "In MM.1S  cells treated with mycolactone and/or BZ  at the indicated concentrations, or vehicle as control for 6 h: (F) Total RNA was isolated and used as a template for RT-PCR of XBP-1 (upper panel) which was then digested with  Pst1  and separated on a 2% agarose gel (lower panel) with molecular weight markers (bp) indicated on the left; spliced XBP1 (sXBP1) mRNA levels were also quantified by qPCR  and normalized to total (spliced + unspliced) XBP1 mRNA levels, (G) BiP  mRNA level were quantified by  qPCR. Data information: Shown mRNA data are Mean fold changes (2-∆∆CT) ± SD, relative to untreated controls (cumulative data of at least 2 independent experiments with technical duplicates or triplicates), pairwise compared by nested one-Way ANOVA with Tukey's multiple comparison test, exact p-values indicated. Thapsigargin (Tg, 2 µM, 6 h), Tunicamycin (Tu, 2 µM, 6 h) were used as positive controls. shown data are representative of 2 independent experiments with similar results.",
    "ncbi_link": "BiP: 3309
XBP-1: 7494
XBP1: 7494"
  },
  {
    "caption": "E ATF4, CHOP, sXBP1 and BiP  mRNA levels were quantified by qPCR in MM.1s BzR cells treated as in (C). sXBP1 mRNA levels were normalized to total (spliced + unspliced) XBP1 mRNA level. Data are Mean RNA fold changes (2-∆∆CT) ± SD, relative to untreated controls. N = 5 (cumulative data of 2 independent experiments with technical duplicates and triplicates), pairwise compared by nested one-Way ANOVA with Tukey's multiple comparison test, exact p-values indicated. Thapsigargin (Tg, 2 µM, 6h) was used as a positive control.",
    "ncbi_link": "ATF4: 468
CHOP: 1649
BiP: 3309
XBP1: 7494"
  },
  {
    "caption": "C  v-abl pro-B cells were treated with  mycolactone and/or BZ  at the indicated concentrations for 6 h. CHOP mRNA levels were quantified by  qPCR. Data are Mean RNA fold changes (2-∆∆CT) ± SD relative to untreated controls. N = 6 (cumulative data of 3 independent experiments with technical duplicates), pairwise compared by nested one-Way ANOVA with Tukey's multiple comparison test, exact p-values indicated. Data information: Thapsigargin (Tg, 2 µM, 6h) was used as a positive control.",
    "ncbi_link": "CHOP: 13198
v-abl: 1491873"
  },
  {
    "caption": "D v-abl pro-B cells were treated for 6 h with mycolactone and/or  BZ  at the indicated concentrations. ATF4 protein levels were assessed in cell lysates by Western blot (top panel) and quantified relative to GADPH levels (lower panel). Data information: Data shown are representative of experiments performed with two independent v-abl cell clones, with similar results. Thapsigargin (Tg, 2 µM, 6h) was used as a positive control.",
    "ncbi_link": "v-abl: 1491873"
  },
  {
    "caption": "D, Scoring of the PI3Kα activation transcriptomic signature was used to cluster patients with high, medium (both groups were combined, high+medium: red) and low (black) scoring levels in the primary tumours of confirmed PDAC patients from PAAD (TCGA) or PACA-AU (BH corrected p-values). The survival curves of each cluster were then plotted, and the statistical significance was calculated using the logrank test.",
    "ncbi_link": "PI3Kα: 18706"
  },
  {
    "caption": "A, Representative images of PI3K activation (as shown by positive pAkt substrate staining) on the primary tumours of PDAC patients, with values of quantification of cfDNA and mutated KRAS allele frequency.",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "N, Tail vein injection experiment in C57/B6 mice of murine syngeneic pancreatic cancer cells (Kras mutated A338, Kras mutated and half PI3Kα inactive, A260; n>8 in each group), quantification of micro- and macro-metastasis at final time point.",
    "ncbi_link": "Kras: 16653
PI3Kα: 18706"
  },
  {
    "caption": "A: Morphology on phase contrast microscopy for parental fibroblast lines (upper panel) and iPSCs (lower panel) from control Detroit 551, WS5A and CP2A POLG patients (scale bars, 50 µm).",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "C: RT-qPCR quantification of gene expression for LIN28A, NANOG, and POU5F1 for all iPSCs from control Detroit 551, WS5A and CP2A POLG patients (n=7, technical replicates per line for ESCs; n=4, technical replicates per clone for control, WS5A and CP2A iPSCs). The gene expression of the individual clones is assessed with fold change using the comparative ΔΔCt method by normalizing iPSCs to ESC1.",
    "ncbi_link": "LIN28A: 79727
NANOG: 79923
POLG: 5428
POU5F1: 5460"
  },
  {
    "caption": "I: Relative mtDNA copy number in Detroit 551, WS5A and CP2A iPSCs by RT-qPCR analysis using ND1 and APP (n=5, technical replicates per clone for control; n=5, technical replicates per clone for WS5A and CP2A). Values are presented as Log2 of the ratio between the expression values of ND1 in relation to APP.",
    "ncbi_link": "APP: 351
ND1: 4535"
  },
  {
    "caption": "A: Quantification of gene expression for NSC markers PAX6, NESTIN and SOX2 for all NSCs from RT-qPCR analysis. The expression of the neural stem cell markers is assessed with fold change using the comparative ΔΔCt method by normalizing NSCs to iPSCs (n=3, technical replicates per ESC line or iPSC clone).",
    "ncbi_link": "NESTIN: 10763
PAX6: 5080
SOX2: 6657"
  },
  {
    "caption": "D: Sequencing chromatogram showing the homozygous c.2243G>C variation in POLG in WS5A iPSC-derived NSCs and the heterozygous c.1399G>A and c.2243G>C variation in POLG in CP2A iPSC-derived NSCs.",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "C: Relative mtDNA copy number analyzed by RT-qPCR using primers and fluorogenic probes for regions of ND1 and nuclear gene APP in all NSCs (n=4, technical replicates per clone for control; n=5, technical replicates per clone for WS5A; n=7, technical replicates per clone for CP2A).",
    "ncbi_link": "APP: 351
ND1: 4535"
  },
  {
    "caption": "F: Relative mtDNA copy number analyzed by RT-qPCR for regions of ND1 and nuclear gene APP in fibroblasts (n=3, technical replicates for control; n=4, technical replicates for WS5A and CP2A).",
    "ncbi_link": "APP: 351
ND1: 4535"
  },
  {
    "caption": "J: Flow cytometric measurement of specific TFAM level (total TFAM/TOMM20) in iPSC-derived DA neurons from Detroit 551 control, WS5A and CP2A POLG patients (n=8, technical replicates per clone for control; n=5, technical replicates per clone for WS5A; n=4, technical replicates per clone for CP2A).",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "K: Relative mtDNA copy number analyzed by RT-qPCR for regions of ND1 and nuclear gene APP in all iPSC-derived DA neurons (n=3, technical replicates per clone).",
    "ncbi_link": "APP: 351
ND1: 4535"
  },
  {
    "caption": "A: Complex I immunohistochemistry in the occipital cortex of a neurologically healthy control (a) and two patients with POLG-disease (b and c) (Scale bar, 20 µm). Patients have numerous complex-I negative neurons (examples marked by arrows). (d) mtDNA relative quantification in microdissected neurons from the occipital cortex of patients with POLG diseases (n=5) and neurologically healthy controls (n=5). Each point represents the mean value of three technical replicates from a pooled sample of 10 neurons. For the purposes of comparison, a control sample has been arbitrarily set to one. The medians of the two groups are compared by Mann-Whitney U test. Data are presented as mean (horizontal bars) ± SEM (vertical bars).",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "(B) WT MEFs or Atg5 (−/−) MEFs from two separate clones were starved for 2 h before treatment with DCFDA and visualization or fluorometric analysis.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A) Upper panel: CHO cells stably transfected with GFP‐GATE‐16 were preincubated in the presence or absence of 10 mM NAC or 1000 μ/ml catalase for 10 min before starvation for 2 h in the presence or absence of these drugs, or grown in a control medium containing the drugs for 2 h. The cells were then fixed, permeabilized and stained with anti‐GFP monoclonal antibodies. Representative images are shown. Lower panel: HEK 293 cells were transfected with GFP‐GATE‐16. At 24 h post‐transfection, the cells were treated with NAC or catalase and starved as explained above, lysed in Ripa buffer and 100 ‐g of each lysate was separated on 10% SDS-PAGE and subsequently analyzed with anti‐GFP antibodies to detect the transfected GATE‐16 and anti‐tubulin antibodies as control. The data were quantified using NIH image program and are depicted as the percentage of lipidated protein from the total GATE‐16. (*) indicates non‐lipidated and (**) indicates lipidated GFP‐GATE‐16.",
    "ncbi_link": "GATE‐16: 11345"
  },
  {
    "caption": "(A) CHO cells (for mammalian Atg8s) or cells of S. cerevisiae (for ScAtg8) were incubated in starvation medium (EBSS or SD‐N, respectively) for different time periods as indicated before isolation of RNA by the Tri‐reagent as explained in Materials and methods. For each gene, data obtained from non‐starved cells were set to an arbitrary value of 1, and results from the corresponding starved cells were normalized accordingly. Results represent the means±s.d. of three separate experiments.",
    "ncbi_link": "ScAtg8: 852200
Atg8: 23710///11345"
  },
  {
    "caption": "(C) CHO cells were grown in a control medium in the presence or absence of 1 mM H2O2 for 1 h, or starved for 3 or 13 h. Lysates (10 μg) obtained in Ripa buffer were incubated with recombinant His6‐GATE‐16‐HA (0.3 μg) in 50 KT reaction buffer (25 mM Tris, pH 7.4, 50 mM KCl) at 30°C for 45 min, in the presence or absence of 1 mM DTT. The reaction was stopped by addition of sample buffer and boiling, after which the samples were resolved on 15% SDS-PAGE and subsequently analyzed by Western blot, using anti‐His monoclonal antibodies. The experiment was repeated six times; a representative blot is shown.",
    "ncbi_link": "GATE‐16: 11345"
  },
  {
    "caption": "(D) Left panel: HeLa cells transfected with Myc‐GATE‐16‐HA or with an empty vector as control were labeled with [35S]methionine for 10 min and lysed immediately or chased for 1 h before lysis in Ripa buffer. Lysates were immunoprecipitated using anti‐Myc antibodies and the immunoprecipitates were resolved on 15% SDS-PAGE. Middle panel: HeLa cells transfected with Myc‐GATE‐16‐HA were kept in control medium or starved for 30 min or 13 h in EBSS before labeling with [35S]methionine for 10 min, immediate lysis, analysis by SDS-PAGE and quantification (right panel) using NIH image program. Values are presented as the average percentage of unprimed form out of the total GATE‐16. (*) in all sections of this figure indicates non‐cleaved His6‐GATE‐16‐HA or Myc‐GATE‐16‐HA and (**) indicates cleaved His6‐GATE‐16 or Myc‐GATE‐16.",
    "ncbi_link": "GATE‐16: 11345"
  },
  {
    "caption": "(A) Cleavage activity was tested by incubation of recombinant His6‐HsAtg4A (0.1 μg) and His6‐GATE‐16‐HA (0.3 μg) in 50 KT reaction buffer at 30°C for 45 min in the presence of indicated concentrations of DTT followed by Western blot analysis, using anti‐His monoclonal antibodies. The resulting bands from three separate experiments were quantified with a densitometer using the Bio‐Rad Multi‐Analyst program and are presented as the average percentage of cleaved form out of the total GATE‐16. (*) indicates non‐cleaved His6‐GATE‐16‐HA and (**) indicates cleaved His6‐GATE‐16.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(B) His6‐HsAtg4A was incubated in the presence of 200 μM DTT at 4°C for 10 min. Reduced His6‐HsAtg4A (0.1 μg) was then incubated in 50 KT (to obtain 15 μM DTT) with the indicated concentrations of H2O2 at 25°C for 5 min, after which recombinant His6‐GATE‐16‐HA (0.3 μg) was added and incubation proceeded at 30°C for 45 min. Reaction mixtures from three separate experiments were analyzed and are presented as explained in (A).",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(C) His6‐HsAtg4A (0.1 μg) was incubated with recombinant His6‐GATE‐16‐HA (0.3 μg) after the following procedures: no treatment (lane 1); pretreatment with 200 μM DTT at 25°C for 5 min (lane 2); treatment with 200 μM DTT followed by treatment with 1 mM H2O2 at 25°C for 5 min (lane 3); and treatment with 200 μM DTT followed by treatment with 1 mM H2O2 for 5 min and then 2 mM DTT (lane 4). Reaction mixtures were analyzed by Western blot using anti‐His monoclonal antibodies.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(A) Recombinant His6‐HsAtg4AWT, His6‐HsAtg4AC77A or His6‐HsAtg4AC81S (0.1 μg) was incubated with His6‐GATE‐16‐HA (0.3 μg) in 50 KT reaction buffer at 30°C for 45 min in the presence or absence of 1 mM DTT. Reaction mixtures were analyzed by Western blot using anti‐His monoclonal antibodies. (*) indicates non‐cleaved His6‐GATE‐16‐HA and (**) indicates cleaved His6‐GATE‐16.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(B) His6‐HsAtg4AC81S (0.1 μg) was incubated with recombinant His6‐GATE‐16‐HA (0.3 μg) following the same procedure as detailed in Figure 5C. Reaction mixtures were analyzed and are presented as explained in (A).",
    "ncbi_link": "GATE‐16: 11345"
  },
  {
    "caption": "(A) CHO cells stably expressing GFP‐GATE‐16 were transiently transfected with HsAtg4AWT‐Myc‐His6 or HsAtg4AC81S‐Myc‐His6. At 24 h post‐transfection, cells were starved for 2.5 h after which they were fixed, permeabilized and incubated with anti‐Myc monoclonal antibodies. Upper panel: typical images of cells transfected with the above constructs, as visualized using a confocal microscope; representative autophagosomes are indicated by arrows. Lower panel: quantification of the average number of autophagosomes per cell in the different transfectants. Images of the fixed cells were visualized using a Nikon eclipse TE300 fluorescent microscope and used for quantification of the number of autophagosomes per cell. The results presented are the means±s.d. of a total of 100 cells from three separate experiments. (*) indicates significance at P0.001.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(B) Left panel: HEK 293 cells were cotransfected with GFP‐GATE‐16 and each of the Atg4A constructs mentioned in (A). At 40 h post‐transfection, the cells were starved for 2.5 h, lysed in Ripa buffer and 100 μg of each lysate was loaded to 10% SDS-PAGE and subsequently analyzed with anti‐GFP antibodies to detect the transfected GATE‐16, anti‐Myc antibodies to detect the transfected HsAtg4A and anti‐tubulin antibodies as control. (*) indicates non‐lipidated GFP‐GATE‐16 and (**) indicates lipidated GFP‐GATE‐16. Right panel: results from three separate experiments, as detailed in the left panel, were analyzed using NIH image program and quantified as follows: the amount of lipidated GFP‐GATE‐16 out of the total of GFP‐GATE‐16 was calculated for each mutant in each experiment. The value obtained for HsAtg4AWT in each experiment was set to 100% and the relative lipidation in cells transfected with the mutant was calculated accordingly.",
    "ncbi_link": "Atg4A: 115201
GATE‐16: 11345"
  },
  {
    "caption": "(A) HeLa cells were transiently transfected with GFP-HsAtg4BWT or GFP‐HsAtg4BC78S. At 24 h post‐transfection, cells were starved for 2.5 h in the presence of 4 mM H2O2 after which they were fixed, permeabilized and incubated with anti‐LC3 polyclonal antibodies. Cells were visualized (upper panel) and quantified (lower panel) as explained in Figure 8. Representative autophagosomes are indicated in the upper panel by arrows. The results presented in the lower panel are the means±s.d. of a total of 100 cells from three separate experiments. (*) indicates significance at P0.001.",
    "ncbi_link": "Atg4B: 23192"
  },
  {
    "caption": "(e,f) Rotenone increased delivery of MitoTracker Green-stained mitochondria (mt) to LysoTracker Red (LTR)-stained lysosomes, inhibited by siRNA knockdown of ATG7 or LC3 in SH-SY5Y cells. Ctrl, control. Right: RNAi knockdown.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(e,f) Treatment with 6-OHDA and CCCP increased surface exposure of CL probed with annexin V in SH-SY5Y (e, 120 μM) and parkin-expressing HeLa cells (f, 20 μM), respectively. Mean ± s.d. of n = 3 independent experiments for c-f (see Supplementary Table S4 for statistics source data); *P0.05 versus vehicle control.",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "(a-e) SH-SY5Y cells expressing control (Ctrl) or scramblase-3 siRNA #508 (PLS3 siRNA) for 72 h were stained with MitoTracker Green FM, a transmembrane potential-independent dye, and treated with rotenone (Rot; 1 μM). Veh, vehicle. (a) Anionic phospholipids exposed to the outer surface of isolated mitochondria were quantified by flow cytometry for Alexa 647-annexin V binding.",
    "ncbi_link": "PLS3: 57048
scramblase-3: 57048"
  },
  {
    "caption": "(a-e) SH-SY5Y cells expressing control (Ctrl) or scramblase-3 siRNA #508 (PLS3 siRNA) for 72 h were stained with MitoTracker Green FM, a transmembrane potential-independent dye, and treated with rotenone (Rot; 1 μM). Veh, vehicle. (b-d) PLS3 knockdown had no effect on rotenone-induced autophagy (b), but decreased mitophagy in SH-SY5Y cells treated with rotenone (c; 1 μM) or 6-OHDA (d; 120 μM).",
    "ncbi_link": "PLS3: 57048
scramblase-3: 57048"
  },
  {
    "caption": "(a-e) SH-SY5Y cells expressing control (Ctrl) or scramblase-3 siRNA #508 (PLS3 siRNA) for 72 h were stained with MitoTracker Green FM, a transmembrane potential-independent dye, and treated with rotenone (Rot; 1 μM). Veh, vehicle. (d,e) The effects of PLS3 siRNA were recapitulated using a second siRNA #433 (d, Supplementary Fig. S3b,g), and reversed by transfection with an RNAi-resistant mouse PLS3 vector (e). Inset: PLS3 overexpression.",
    "ncbi_link": "PLS3: 57048
PLS3: 70310
scramblase-3: 57048"
  },
  {
    "caption": "(f-i) Primary neurons transfected for 72 h with CLS siRNA or scrambled control siRNA were treated with rotenone (250 nM) and analysed for autophagy (Supplementary Fig. S1b) or mitophagy by either co-localization analysis (f)",
    "ncbi_link": "CLS: 366196"
  },
  {
    "caption": "(f-i) Primary neurons transfected for 72 h with CLS siRNA or scrambled control siRNA were treated with rotenone (250 nM) and analysed for autophagy (Supplementary Fig. S1b) or mitophagy by either co-localization analysis (f), or with mitochondrial protein immunoblotting (g) and densitometry (h,i and Supplementary Fig. S4c). Knockdown efficiencies are shown in Supplementary Figs S3 and S4. Mean ± s.d. of n = 4 independent experiments for b,c, and n = 3 independent experiments for a,d-f,h-i (see Supplementary Table S4 for statistics source data); *P0.05 versus vehicle; †P0.05 versus toxin-treated control siRNA; **P0.05 versus Rot/PLS3 siRNA. See Supplementary Fig. S7 for uncropped blots.",
    "ncbi_link": "CLS: 366196"
  },
  {
    "caption": "(d) Cell lysates from stable PINK1-Flag-expressing SH-SY5Y cells were treated with 6-OHDA (120 μM), rotenone (1 μM) or FCCP (2 μM), and analysed by Flag immunoblot for PINK1-Flag levels.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(e) SH-SY5Y cells transfected with HA-parkin were treated with the indicated toxins, immunolabelled for HA (green) and mitochondrial p60 antigen (red) and analysed for HA-parkin redistribution to mitochondria. FCCP elicited translocation of parkin to mitochondria (arrows), which was not seen with the other mitophagy stimuli.",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "(f-j) The arrowhead in e shows the position of the N-terminal truncation used to create GFP-LC3 deletion mutants, which were analysed for GFP-LC3 puncta formation (f,g,i) and participation in mitophagy (h,j) in response to the indicated stimuli. Rot, rotenone; Veh, vehicle.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "B. The predicted PUB domain in the N-terminus of SPATA2 interacts with CYLD, but not with LUBAC or other TNF-RSC components. GFP-SPATA2 and the indicated deletion mutants were purified from A549 cells that were stimulated with TNF-α for 15 minutes, and the enriched proteins were quantified using SILAC-based MS.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "C. Validation of SPATA2 N-terminus interaction with CYLD. GFP-SPATA2 and the indicated deletion mutants were purified from A549 cells as described in Figure 5A, and association of CYLD was analyzed by immunoblotting. The lower panels show controls.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "D. The USP domain of CYLD interacts with SPATA2. STREP-FLAG-CYLD and the indicated deletion mutants were purified from A549 cells using Step-Tactin sepharose and blotted with SPATA2 antibody. The lower panels show controls.",
    "ncbi_link": "CYLD: 1540"
  },
  {
    "caption": "E. The C-terminus of SPATA2 interacts with HOIP. A549 cells were transiently transfected with GFP-tagged SPATA2, SPATA2 D200 and SPATA2 200*, and SPATA2 and the mutants were immunoprecipitated using GFP-trap beads. The immunoprecipitates were immunoblotted with HOIP, CYLD and GFP (HOIP) antibodies. The lower panels show input control, and the * shows unspecific band.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "B. Effect of SPATA2 knockdown on association of proteins with TNF-RSC. The list shows SILAC ratios of TNF-RSC-associated proteins in control cells and SPATA2 knockdown cells. The proteins that showed reduced association with the TNF-RSC after SPATA2 knockdown are highlighted red.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "C. Validation of SPATA2-dependent association of CYLD with the TNF-RSC. The TNF-RSC was purified under the indicated conditions and association of SPATA2, CYLD, RIPK1 and HOIP with the TNF-RSC was analyzed by immunoblotting. The input controls show expression of the analyzed proteins in cell lysates. The asterisk denotes unspecific bands.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "A. SPATA2 regulates TNF-a-induced NF-κB activation. HEK293T cells were transfected with the SPATA2 siRNA (SMARTpool or with to individual siRNA) or a non-targeting control siRNA, and NF-kB activation was monitored with luciferase-based NF-kB reporter assays. Error bars specify the standard error of the mean (SEM) of three independent experiments. p** < 0.05 (two-tailed, unpaired Student´s t-test).",
    "ncbi_link": "luciferase: 
NF-kB: 
NF-κB: 
SPATA2: 9825"
  },
  {
    "caption": "B. Knockdown of SPATA2 enhances expression of the NF-κB target genes. HEK293T cells were transfected with SPATA2 siRNA or a non-targeting control siRNA and the expression of the indicated mRNAs was measured in cells stimulated with TNF-a for 0, 3 and 6 hours with qPCR.",
    "ncbi_link": "SPATA2: 9825"
  },
  {
    "caption": "C. SPATA2 is involved in TNF-α-induced necroptosis. SPATA2 was knocked down in L929 cells using RNAi, and cells were pretreated with DMSO, Z-VAD, or Z-VAD+NEC1 for 1 hour followed by treatment with TNF-α for 2.5 hours. Cell viability was assessed with propidium iodide staining and flow cytometry. Knockdown of SPATA2 mRNA was verified using real time PCR. p** < 0.05 (two-tailed, unpaired Student´s t-test).",
    "ncbi_link": "SPATA2: 263876"
  },
  {
    "caption": "D. Knockdown of SPATA2 reduces phosphorylation of MLKL in TNF-α-induced necroptosis. TNF-α-dependent necroptosis was induced in L929 as described in Figure 6C. Phosphorylation of MLKL was analyzed using S358 phospho-specific antibody.",
    "ncbi_link": "SPATA2: 263876"
  },
  {
    "caption": "(A) OCR of wt and gas-1 mutant nematodes (normalized to nematode size as given by the COPAS Biosort (Time of Flight -TOF)). One representative curve shown (mean ± SEM; n=3) ****p value< 0.0001; Kruskal-Wallis Test, Dunn's post hoc correction.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "Representative curves show the lifespan of wt and gas-1(fc21) nematodes compared to (B) age-1 and age-1; gas-1 mutants animals. Average median lifespans ± SEM from all replicates indicated beneath representative curves.",
    "ncbi_link": "age-1: 174762
fc21: 181646
gas-1: 181646"
  },
  {
    "caption": "Representative curves show the lifespan of wt and gas-1(fc21) nematodes compared to (C) daf-16 and daf-16; age-1; gas-1 mutant animals. Average median lifespans ± SEM from all replicates indicated beneath representative curves.",
    "ncbi_link": "age-1: 174762
daf-16: 172981
fc21: 181646
gas-1: 181646"
  },
  {
    "caption": "(D) Volcano plot of differentially phosphorylated proteins in gas-1(fc21) mutants compared to wt. Cutoffs: 20% FDR and |log2(foldchange)| >0.345 (in red).",
    "ncbi_link": "fc21: 181646
gas-1: 181646"
  },
  {
    "caption": "(F) Lifespan analysis of mev-1(kn1) nematodes compared to wt, age-1(hx546) and age-1(hx546); mev-1(kn1) animals. (G)",
    "ncbi_link": "age-1: 174762
hx546: 174762
kn1: 260040
mev-1: 260040"
  },
  {
    "caption": "(G) ATP measurements in wt, age-1, gas-1 and age-1; gas-1 mutant nematodes (normalized to wt), n=4. Error bars: Mean ± SEM, *p value <0.05, ***p value =0.001, Kruskal-Wallis Test, Dunn's post hoc correction.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(H) OCR of gas-1 and age-1; gas-1 mutant nematodes (normalized to TOF). Left panel: One representative curve (Mean ± SEM). Right panel: Basal respiration in wt, gas-1 and age-1; gas-1 animals, pooled from 3 biological replicates, ****p value <0.0001, ns= non-significant, Kruskal-Wallis Test, Dunn's post hoc correction.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(K) Representative lifespan of age-1; gas-1 nematodes fed with empty vector (EV) and fzo-1 RNAi bacteria. Average median lifespans ± SEM from all replicates indicated beneath representative curves. For all panels: wt= wild type, a= age-1, g= gas-1, a; g= age-1; gas-1.",
    "ncbi_link": "age-1: 174762
fzo-1: 173990
gas-1: 181646"
  },
  {
    "caption": "(A) Left panel: Venn Diagram of the number of genes significantly dysregulated in age-1; gas-1 versus wt (green) and gas-1 versus wt (red). Right panel: Scatter-plots of the expression of genes significantly downregulated (left) or upregulated (right) in gas-1 and age-1; gas-1 mutants compared to wt. In black: expression levels of genes that are significantly up- or down-regulated in gas-1 mutants compared to wt. In red: expression levels of the same genes in age-1; gas-1 mutants compared to wt.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(D) Volcano plot of TMT/iTRAQ-based quantitative proteomic analysis. In red, proteins significantly dysregulated in age-1; gas-1 compared to gas-1 (FDR< 20%; |log2 (fold change)| >0.47). Dashed lines indicate cutoffs. Proteins involved in carbohydrate (green) and lipid (blue) metabolism are labeled.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(H) Left panel: Glucose quantification in wt, gas-1 and age-1; gas-1 nematode lysates with NMR, n=7, ns= non-significant, Mann Whitney U test. Right panel: Quantification of total carbohydrates in the indicated strains with phenol-sulfuric assay. Error bars: mean ± SEM, 2 biological replicates (5 technical replicates each), normalized to wt and number of animals used. **p value < 0.01, ns= non-significant, Mann-Whitney U test.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(C) Immunoblot analysis of phospho-AAK-2 in wt, age-1, gas-1 and age-1; gas-1 mutant nematodes (actin loading control). Numbers correspond to band densitometries across 3 biological replicates.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(D) Representative lifespan of age-1; gas-1 double mutant and age-1; aak-2; gas-1 triple mutant nematodes with average median lifespans ± SEM from all replicates indicated beneath representative curves.",
    "ncbi_link": "aak-2: 181727
age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "(E) Lifespan assay of gas-1 mutant animals compared to gas-1; AAK-2 overexpressing (O/E) nematodes and their wt counterparts. Inset: immunoblot analysis of phospho-AAK-2 in gas-1 (g) and gas-1; AAK-2 O/E (g; a O/E) animals (actin loading control), showing the overexpressed protein (lower band) and the endogenous one (upper band).",
    "ncbi_link": "AAK-2: 181727
gas-1: 181646"
  },
  {
    "caption": "(F) Left panel: Immunoblot analysis of phospho-KIN-1 substrates in young adult nematodes. Numbers correspond to band densitometries across 2 biological replicates. Right panel: immunoblot analysis of phospho-KIN-1 substrates in age-1; gas-1 animals grown on bacteria carrying an empty vector (EV) or expressing kin-1 RNAi. Two different kin-1 RNAi clones (g1, b5) were used in this experiment. Numbers correspond to band densitometries of the presented immunoblot. Dashed rectangles: band corresponding to downregulated KIN-1 phospho-substrate.",
    "ncbi_link": "age-1: 174762
gas-1: 181646
kin-1: 3565407"
  },
  {
    "caption": "(G) Representative lifespan assay of wt and age-1; gas-1 nematodes fed with empty vector (EV) and kin-1 RNAi bacteria with average median lifespans ± SEM from all replicates indicated beneath representative curves.",
    "ncbi_link": "age-1: 174762
gas-1: 181646
kin-1: 3565407"
  },
  {
    "caption": "ATP measurements in: (H) age-1(hx546); gas-1(fc21) (a; g) and age-1(hx546); aak-2(ok524); gas-1(fc21) (a; aa; g) mutant nematodes;",
    "ncbi_link": "aak-2: 181727
ok524: 181727
age-1: 174762
hx546: 174762
fc21: 181646
gas-1: 181646"
  },
  {
    "caption": "ATP measurements in: (I) age-1; gas-1 (EV) (a; g (EV)) and age-1; gas-1; kin-1 (RNAi) (a; g; kin-1(RNAi)). Error bars: Mean ± SEM, n=4, *p value <0.05, Mann Whitney U test.",
    "ncbi_link": "age-1: 174762
gas-1: 181646
kin-1: 3565407"
  },
  {
    "caption": "(J) Left panel: curves represent FRAP in age-1; gas-1 animals grown on RNAi from larval L1 (or from egg for fzo-1 RNAi) to L4 stage. Each point: mean recovery of bleached regions (2-5 regions per animal, 10-20 animals per condition) ± SEM. Right panel: Maximum (total) recovery per condition are shown, ± SEM. *p value< 0.05, **p value< 0.01, ****p value< 0.0001, Kruskal-Wallis test, Dunn's post-hoc correction.",
    "ncbi_link": "age-1: 174762
fzo-1: 173990
gas-1: 181646"
  },
  {
    "caption": "A) Volcano plot of lipidomic profiling in gas-1 versus age-1; gas-1 mutants. Red stars: significantly altered lipids in age-1; gas-1 versus gas-1 (5% FDR; n=5).",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "B) NMR-1D targeted metabolic profiling in age-1; gas-1 mutants (normalized to gas-1). Dashed lines indicate fold change cutoff (|log2(fold change)| <1.23). Red bars: not significant, Light blue bars: FDR<10%, |log2(fold change)| <1.23, Dark blue bars: FDR <10%, |log2(fold change)| >1.23. Error bar: mean + SEM, n=7.",
    "ncbi_link": "age-1: 174762
gas-1: 181646"
  },
  {
    "caption": "D) Left panel: qRT-PCR of xdh-1 (normalized to wt). Error bars: Mean ± SEM, n=6. ****p value< 0.0001, *p value< 0.05, ns= non-significant, Kruskal-Wallis with Dunn's post hoc test. Right: xanthine oxidase activity levels normalized to animal number. Error bars: mean ± SEM, n=2, ns= non-significant, Mann Whitney U test.",
    "ncbi_link": "xdh-1: 178381"
  },
  {
    "caption": "F) Immunoblot analysis of phospho-Akt (S473), pan Akt, phospho-PRAS40 (T246) and total PRAS40 in WT and NDUFA9 KO HAP1 cells treated with 0.2% DMSO (-) or AMP (2 μM), ENPF (2 μM) and PTX (36 μM) (+) for 24 h (actin loading control).",
    "ncbi_link": "NDUFA9: 4704"
  },
  {
    "caption": "(G) Immunoblot analysis of phospho-PKA substrates in WT and NDUFA9 KO HAP1 cells treated as indicated (actin loading control). For all immunoblot panels: numbers correspond to band densitometries across 2-3 biological replicates.",
    "ncbi_link": "NDUFA9: 4704"
  },
  {
    "caption": "(B) Locomotory activity of 10-day-old gas-1 mutant nematodes treated with vehicle (DMSO) or methylxanthines. Values represent arbitrary units from 3 biological replicates with 4 technical replicates each, 35 worms per technical replicate. Error bars: mean ± SEM, **p value< 0.01, ***p value< 0.001, one-way ANOVA, Dunnett's post-hoc correction.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(C) Effect of methylxanthines on the survival of gas-1 mutants. Average median lifespans ± SEM from all replicates indicated beneath representative curves.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(D) Pharyngeal pumps/minute in young adult gas-1 mutant nematodes treated with vehicle or methylxanthines. Error bars: mean ± SEM, n=18. ****p value< 0.0001, one-way ANOVA, Dunnett's post-hoc correction.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(E-F) Immunoblot analysis of (E) KIN-1 phospho-substrates in young adult gas-1 mutant nematodes treated with vehicle (DMSO) or methylxanthines (actin loading control).",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(E-F) Immunoblot analysis of (F) phospho-AAK-2 in young adult gas-1 mutant nematodes treated with vehicle (DMSO) or methylxanthines (actin loading control).",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(G) Left panel: FRAP in vehicle or PTX-treated gas-1 animals. Each point: mean recovery of 14 bleached regions (2 regions per animal, 7 animals per condition) ± SEM. Right panel: maximum (total) recovery per condition ± SEM. **p value< 0.01 unpaired t test. For all immunoblot panels: numbers correspond to band densitometries across biological replicates and for all lifespan curves: the legend shows Mean median lifespan ± SEM across all biological replicates.",
    "ncbi_link": "gas-1: 181646"
  },
  {
    "caption": "(A) Imaging of FoxO3‐mediated modification of the mitochondrial network in soleus muscle of living mice. Adult soleus muscles were transfected with pDsRed2‐Mito and either c.a.FoxO3 or mock vector (control). Two weeks later, muscles were exposed and observed in situ using two‐photon microscopy. At least five animals per condition were studied.",
    "ncbi_link": "FoxO3: 56484"
  },
  {
    "caption": "(B) Overexpression of c.a.FoxO3 induces mitochondrial changes and removal through autophagy. Muscle fibres were transfected by electroporation with YFP‐LC3, pDsRed2‐Mito and either c.a.FoxO3 or mock vector. Two weeks later, fluorescent fibres were analysed for mitochondrial distribution by confocal microscopy. A higher magnification of the square is depicted on the right panels. White arrows point autophagosomes engulfing the mitochondria.",
    "ncbi_link": "FoxO3: 56484"
  },
  {
    "caption": "(C) Overexpression of c.a.FoxO3 induces reduction in myofibre size and decrease in SDH staining. Left image: immunostaining for FoxO3 shows atrophic fibres, which over‐expressed FoxO3 (red) and are labelled by asterisks. Nuclei are stained by Hoechst (blue). Right image: histochemistry for succinate dehydrogenase (SDH) on serial section. Note that fibres positive for FoxO3 are negative for SDH staining (asterisks).",
    "ncbi_link": "FoxO3: 56484"
  },
  {
    "caption": "(D) Electron micrograph of a control and c.a.FoxO3‐expressing fibres. Muscles were processed with standard fixation‐embedding procedure. Black and white arrows indicate subsarcolemmal and intermyofibrillar mitochondria, respectively. Note that subsarcolemmal mitochondria are reduced in FoxO3 overexpressing fibres, whereas intermyofibrillar mitochondria are smaller and paler than control ones. Red arrowheads show a vesicle containing mitochondria. The image is representative of the FoxO3‐transfected fibres.",
    "ncbi_link": "FoxO3: 56484"
  },
  {
    "caption": "(A) RNAi‐mediated knockdown of Fis1 showed by western blot assay. MEF cells were transfected with vectors expressing four different Fis shRNAs. For in vivo experiments Fis (4) was used. Efficiency of protein knockdown is indicated in Supplementary Table S2.",
    "ncbi_link": "Fis1: 66437"
  },
  {
    "caption": "(B) Blockade of Fis1 and of Bnip3 by RNAi reduces muscle loss during fasting. Adult skeletal muscles were transfected with specific shRNAs for mouse Fis1 (oligo 4) and mouse Bnip3 or co‐transfected and 8 days later mice were starved for 48 h. Cross‐sectional area (CSA) of transfected fibres, identified by GFP, was measured as described earlier (*P0.01) n=450.",
    "ncbi_link": "Bnip3: 12176
Fis1: 66437"
  },
  {
    "caption": "(C) RNAi of Fis1 and Bnip3 significantly prevents MuRF‐1 and atrogin‐1 promoters activation during starvation. TA muscles were transfected with either 5 kb of the MuRF‐1 promoter (left panel) or 3.5 kb of atrogin‐1 promoter (right panel) with or without shRNAs vectors against Fis and Bnip3. In fasting experiments, after 7 days from transfection mice were starved for 24 h. A renilla‐luciferase construct (pRL‐TK) was co‐transfected to normalized for transfection efficiency. The activation of MuRF‐1 and atrogin‐1 promoters was determined by firefly activity and normalize for the renilla. Each condition represents the average of at least three independent experiments±s.e.m. (*P0.05).",
    "ncbi_link": "firefly: 
renilla: 
Bnip3: 12176
atrogin‐1: 67731
Fis1: 66437
MuRF‐1: 433766"
  },
  {
    "caption": "(D) Muscle atrophy induced by FoxO3 is reduced by d.n.DRP1. Adult skeletal muscles were transfected with HA‐tagged c.a.FoxO3 with or without d.n.DRP1 and examined after 2 weeks. CSA of transfected fibres, identified by anti‐HA immunofluorescence, was measured as described earlier (*P0.001) n=400.",
    "ncbi_link": "DRP1: 74006
FoxO3: 56484"
  },
  {
    "caption": "(E) Blockade of the fission machinery by d.n.DRP1 or Bnip3 inhibition by RNAi reduces FoxO3‐mediated autophagosome formation. Animals were transfected with YFP‐LC3, c.a.FoxO3 in presence or absence of d.n.DRP1 or shRNAs against Bnip3. Twelve days later, muscles were collected and analysed for fluorescent vesicles formation (*P0.001) n=450.",
    "ncbi_link": "Bnip3: 12176
DRP1: 74006
FoxO3: 56484"
  },
  {
    "caption": "(F) FoxO3‐dependent activation of MuRF‐1 and atrogin‐1 is significantly reduced by inhibition of the fission machinery. MuRF‐1 promoter (left panel) or atrogin‐1 promoter (right panel) was co‐transfected into adult TA muscle with or without c.a.FoxO3 and in the presence or absence of d.n.DRP1. A renilla‐luciferase vector was co‐transfected to normalize for transfection efficiency. Eight days later, firefly and renilla‐luciferase activity was determined. Each condition represents the average of at least three independent experiments±s.e.m. (*P0.05).",
    "ncbi_link": "firefly: 
renilla: 
DRP1: 74006
atrogin‐1: 67731
FoxO3: 56484
MuRF‐1: 433766"
  },
  {
    "caption": "Overexpression of DRP1/Fis1 and Bnip3 proteins induces changes in the mitochondrial network in vivo. In vivo imaging of the mitochondrial network was performed in muscles expressing Bnip3, an atrophy‐related gene under FoxO3 control, and DRP1/Fis1 proteins. Adult muscles were transfected with plasmids encoding mitochondrially targeted yellow fluorescent protein (mtM13‐YFP) and either mock vector, Bnip3, HA‐DRP1, Fis1 or DRP1/Fis1. Seven days later (for Bnip3) or 12 days later (for DRP1 and Fis1), muscles were observed in vivo with confocal microscopy. TMRM was injected into the muscles to monitor mitochondria, which retain membrane potential. Muscles transfected with mtM13‐YFP and mock vector showed the orderly pattern of intermyofibrillar and subsarcolemmal mitochondria (upper panel‐IMF). Scale bar: 20 μm.",
    "ncbi_link": "Bnip3: 12176
DRP1: 74006
Fis1: 66437
FoxO3: 56484"
  },
  {
    "caption": "(A) Adult TA muscles were transfected with either DRP1, Fis1, DRP1 and Fis1 or mock vector. Muscles were collected 12 or 21 days after transfection and cross‐sectional area of transfected fibres, identified by immunofluorescence, was measured as described earlier (*P0.001) n=400.",
    "ncbi_link": "DRP1: 74006
Fis1: 66437"
  },
  {
    "caption": "(B) Bnip3 or Bnip3 l expression for 7 days causes a 20% reduction of the cross‐sectional area. TA muscles were transfected with Bnip3, Bnip3l or mock vector. Cross‐sectional area of transfected fibres, identified by immunofluorescence, was analysed (*P0.001) n=500.",
    "ncbi_link": "Bnip3: 12176
Bnip3 l: 12177
Bnip3l: 12177"
  },
  {
    "caption": "(C) Quantification of LC3‐positive autophagic vesicles in adult muscles co‐tranfected with YFP‐LC3 and DRP1, Fis1 or DRP1/Fis1 expression plasmids or mock vector.",
    "ncbi_link": "DRP1: 74006
Fis1: 66437"
  },
  {
    "caption": "(D) Mutations in BH3 domain of Bnip3 (Bnip3BH3mut) do not affect BNIP3‐mediated autophagy. Adult muscles were co‐transfected with YFP‐LC3 and Bnip3 or Bnip3BH3mut expression plasmids and LC3‐positive vesicles were quantified.",
    "ncbi_link": "Bnip3: 12176
LC3: 67443///66734"
  },
  {
    "caption": "(E) Bnip3‐mediated atrophy is not modified by mutating the BH3 domain (Bnip3BH3mut). Adult TA muscles were transfected with Bnip3 or Bnip3BH3mut expression plasmids and cross‐sectional area was quantified 7 days later and plotted as % of controls (*P0.001) n=440.",
    "ncbi_link": "Bnip3: 12176"
  },
  {
    "caption": "(A)In vivo imaging of the mitochondrial network was performed in muscles expressing Fis1K148R. Adult muscles were transfected with plasmids encoding mitochondrially targeted yellow fluorescent protein (mtM13‐YFP) and Fis1K148R. Twelve days later muscles were observed in vivo with confocal microscopy. TMRM was injected into the muscles to monitor mitochondria, which retain membrane potential. Mitochondrial network was greatly altered but mitochondrial membrane potential was conserved.",
    "ncbi_link": "Fis1: 66437"
  },
  {
    "caption": "(C) hFisK148R‐transfected muscles were collected 12 and 21 days after transfection. Cross‐sectional area of transfected fibres, identified by anti‐myc immunofluorescence, was quantified (n=550).",
    "ncbi_link": "Fis: 51024"
  },
  {
    "caption": "(D) Fis1‐dependent activation of MuRF‐1. MuRF‐1 promoter was co‐transfected into adult TA muscle with or without Fis1 or Fis1K148R. A renilla‐luciferase vector was co‐transfected to normalize for transfection efficiency. Eight days later, firefly and renilla‐luciferase activity was determined. Each condition represents the average of at least five independent experiments±s.e.m. (*P0.05).",
    "ncbi_link": "firefly: 
renilla: 
Fis1: 66437
MuRF‐1: 433766"
  },
  {
    "caption": "(A) Left panel: mitochondrial fission activates AMPK. HEK293 cells were transfected with a mock vector (control), Bnip3, DRP1, Fis1 or co‐transfected with DRP1 and Fis1. Cells were collected 24 h later and lysates were analysed by immunoblotting. Right panel: immunoblotting analysis shows AMPK phosphorylation in EDL and soleus muscles during muscle atrophy. P‐AMPK/AMPK ratio analysed by densitometric analysis is indicated below the panels. (B-E) Inhibition of AMPK blocks Bnip3‐ and DRP1/Fis1‐mediated atrophy.",
    "ncbi_link": "Bnip3: 664
DRP1: 10059
Fis1: 51024"
  },
  {
    "caption": "(B) Adult TA muscles were transfected with Bnip3 together with d.n.AMPK or mock vector and cross‐sectional area was measured (*P0.001) n=480.",
    "ncbi_link": "Bnip3: 12176
AMPK: 108079///105787"
  },
  {
    "caption": "(C) Adult TA muscles were transfected with DRP1 and Fis1 together with d.n.AMPK or mock vector. Twelve days later muscles were collected and cross‐sectional area was quantified (*P0.001) n=400.",
    "ncbi_link": "DRP1: 74006
Fis1: 66437
AMPK: 108079///105787"
  },
  {
    "caption": "(D, E) RNAi‐mediated knockdown of AMPK α 1 and α 2 inhibits Bnip3‐ and DRP1/Fis1‐dependent atrophy. Mouse TA muscles were co‐transfected with Bnip3 or DRP1 and Fis1 and pSuper vectors expressing shRNAs against lacZ (control) or AMPK. Twelve days later, TA muscles were collected and the cross‐sectional area was quantified (*P0.001) n=450.",
    "ncbi_link": "Bnip3: 12176
DRP1: 74006
Fis1: 66437
AMPK α 1: 105787
AMPK: 108079///105787"
  },
  {
    "caption": "(C) FoxO3 binding to atrogin‐1 and MuRF‐1 promoters, as determined by ChIP, is induced by AICAR treatment.",
    "ncbi_link": "atrogin‐1: 67731
MuRF‐1: 433766"
  },
  {
    "caption": "(D) RNAi‐mediated knockdown of FoxO3 inhibits DRP1/Fis1‐dependent atrophy. Mouse TA muscles were co‐transfected with DRP1 and Fis1 and pSuper vectors expressing shRNAs against either lacZ (control) or FoxO3. Twelve days later, muscles were collected and the cross‐sectional area was quantified (*P0.001) n=450.",
    "ncbi_link": "DRP1: 74006
Fis1: 66437
FoxO3: 56484"
  },
  {
    "caption": "A-H LM2-4luctumor cells were implanted intravenously into SCIDmice, generating predominantly lung-specific metastases in one experiment (n = 5-6; A-D) and predominantly lymphatic-specific metastases in another experiment (n = 12; E-H). (C and G) Photographs of typical metastases in the lungs and caudal lymphatics, respectively. Kaplan-Meier survival analysis showed that Vasculotide (VT) significantly delayed mortality due to lungmetastases (A) but not lymphaticmetastases (E). Quantitative analysis of in vivo bioluminescent images taken at 24DPI (B) showed that concurrent VT treatment effectively reversed the sunitinib (SU)-induced acceleration of lungmetastases (D). With regard to lymphaticmetastases (F, H), SU treatment did not accelerate their progression. Geometric means ± 95%CI are depicted in (D and H); P values were derived by one-way ANOVA (D) and Kruskal-Wallis test (H). The same trends were reproduced in confirmatory experiments summarized in Supplementary Fig S5.",
    "ncbi_link": "luc: "
  },
  {
    "caption": "A-D An experiment where HT29luc tumor cells were implanted intravenously into YFP-SCID mice. (A) Kaplan-Meier survival analysis. (B) Quantification of total metastatic burden in the liver and lymphatics, at 35 days post-implantation (DPI), from whole-body bioluminescent imaging (C). (D) Photograph of typical liver metastases.",
    "ncbi_link": "luc: "
  },
  {
    "caption": "E-G An experiment where SN12luc tumor cells were implanted intravenously into YFP-SCID mice. (E) Kaplan-Meier survival analysis. (F) Quantification of total metastatic burden at 50DPI, mostly within the lungs, from whole-body bioluminescent imaging (G).",
    "ncbi_link": "luc: "
  },
  {
    "caption": "A, B In modified Boyden chamber experiments, confluent dermal HMVECs were stimulated with tumor cell-conditioned media (TC-CM)-that is, media conditioned by either LM2-4luc, SN12luc, or HT29luc tumor cells-and treated with 20 ng/mL Vasculotide vs. 400 ng/mL Ang1 (positive control) vs. PBS (negative control). Meta-analyses of treatment effects on dextran permeability (A) and tumor cell migration (B), where each datapoint represents the mean of an independent experiment, averaged over 2-3 biological replicates (inserts) per treatment group and normalized internally within that same experiment. Statistical significance of overall Ang1 or VT treatment effects was determined by paired t-tests, n = 11 (A) or 6 (B) experimental replicates.C Representative fluorescent images (10×) of 'extravasated' CMTPX-labeled TCs (red) fixed on membrane undersides.",
    "ncbi_link": "luc: "
  },
  {
    "caption": "D LM2-4luc produced the highest levels of VEGF and IL-8, but lower levels of IL-6, compared to other TC types; ***P < 0.001 and *P < 0.05 (unpaired t-tests).",
    "ncbi_link": "luc: "
  },
  {
    "caption": "A-C Vasculotide (VT) did not alter the growth kinetics of orthotopic LM2-4luc tumors; n = 8 mice per group. Sunitinib (SU) treatment significantly lowered primary tumor burden as measured by volume (B: one-way ANOVA, P < 0.01) or bioluminescent activity (C: one-way ANOVA, P < 0.001).",
    "ncbi_link": "luc: "
  },
  {
    "caption": "G Human LM2-4luc cells can be identified on histological sections of mouse lung tissue by IHC staining of human vimentin, a cytoskeletal protein. Size distribution analysis show VT monotherapy reducing the occurence of bigger metastatic nodules.",
    "ncbi_link": "luc: "
  },
  {
    "caption": "A. Plx1 and PP2A-B56 competes for Apc1-loop500. MBP-fused Apc1-loop500 WT or its derivatives (∆11, deletion of 11 residues including the B56-binding motif) was incubated with the 35S-labelled Flag-B56γ in anaphase extracts supplemented with non-degradable cyclin B at 23˚C for 1 h, and further incubated with indicated amounts of WT Plx1-PBD or Plx1-PBD Pincer mutant (Pin) for 15 min. The bound proteins were recovered by amylose beads, separated by SDS-PAGE and detected by autoradiography or Coomassie brilliant blue (CBB) staining.",
    "ncbi_link": "Plx1: 380481"
  },
  {
    "caption": "(B) HEK293T cells were transfected with SFB control, SFB-tagged PR130 and SFB-B56δ, and the cell lysates were pulled down using streptavidin beads and the interaction of endogenous PPM1G was detected by western blot (WB).",
    "ncbi_link": "PR130: 5523
B56δ: 5528"
  },
  {
    "caption": "(D) HEK293T cells were transfected with SFB control, SFB- PPP2CA, SFB-PPP2CB, SFB-PPP2R1A, SFB-PPP2R1B and SFB- B56δ, and the lysates were pulled down using streptavidin beads and the interaction of endogenous PPM1G was detected by western blot using PPM1G antibody.",
    "ncbi_link": "PPP2CA: 5515
PPP2CB: 5516
PPP2R1A: 5518
PPP2R1B: 5519
B56δ: 5528"
  },
  {
    "caption": "(E) Cell lysates from HEK293T cells expressing SFB vector, SFB-B56α, SFB-B56β, SFB-B56γ, SFB-B56δ and SFB-B56ε were pulled down and interaction with PPM1G was detected by western blotting using PPM1G antibody.",
    "ncbi_link": "B56α: 5525
B56β: 5526
B56γ: 5527
B56δ: 5528
B56ε: 5529"
  },
  {
    "caption": "(G) Cells expressing B56δ full length (FL), Δ91-102, L183A and H282A mutants were pulled down with streptavidin beads and interaction with PPM1G was detected by western blotting.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(H) Various mutants of B56δ were transfected along with myc-PPP2R1A and pulled down using streptavidin beads and interaction with myc-PPP2R1A was detected by immunoblotting.",
    "ncbi_link": "myc: 
PPP2R1A: 5518
B56δ: 5528"
  },
  {
    "caption": "(A) MCF7 and MDA-MB-231 cells transfected with MYC-B56δ were fixed and imaged using a confocal microscope after staining with antibodies against MYC tag and PPM1G to determine PPM1G localization. Representative images from three independent experiments are shown, Scale bars 5 µm. (B) Quantification of cytoplasmic to nuclear (Cyto/Nuc) ratio of PPM1G intensity per each cell was plotted (n=35 for MCF-7 cells; n=25 for MDA-MB-231 cells). Error bars indicate SD. ***p < 0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "MYC: 
B56δ: 5528"
  },
  {
    "caption": "(C) Western blot showing expression levels of SFB tagged B56δ along with endogenous B56δ using in dicated antibodies.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(D) Cells expressing either vector or SFB-B56δ were fractionated into nuclear and cytoplasmic fractions and levels of indicated proteins were determined using western blotting. Tubulin and Histone H3 were used to mark cytoplasmic and nuclear fractions respectively.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(E) Cells treated with control or B56δ shRNA were fractionated into cytoplasmic and nuclear fractions and levels of indicated proteins were determined using immunoblotting. Tubulin and Histone H3 were used to mark cytoplasmic and nuclear fractions respectively.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(F) Localization of PPM1G in cells expressing either empty vector (control), full length B56δ (FL) or various indicated mutants was determined by confocal imaging after staining with Flag and Myc antibodies. Representative images from two independent experiments are shown, Scale bars 10 µm. (G) Cytoplasmic to nuclear (Cyto/Nuc) ratio of PPM1G intensity per each cell expressing either vector, B56δ full length (FL) or mutant versions was quantified and plotted (n=10). Error bars represents SD. ***p < 0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(B) SFB-PPM1G was transfected in both Control shRNA and B56δ shRNA cells and pulled down using streptavidin beads. Interaction with α-catenin was determined by western blotting.",
    "ncbi_link": "PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(C) In vitro phosphorylated MBP-tagged α-Catenin was incubated with equal amounts of bacterially purified recombinant wild type and catalytically inactive mutant (D496A) of PPM1G and the amount of released phosphate was assayed colorimetrically using the malachite green reagent (A620 nm). Data represents mean absorbance from three independent experiments. Error bars indicate SD, **p<0.01 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "PPM1G: 5496"
  },
  {
    "caption": "(E) MDA-MB-231 breast cancer cells were transfected with vector, wild type PPM1G or catalytically inactive PPM1G D496A (D/A) mutant. Levels of phosphorylated α-catenin were detected by using phospho-specific antibodies.",
    "ncbi_link": "PPM1G: 5496"
  },
  {
    "caption": "(F) Cells treated with control shRNA and PPM1G specific shRNAs were lysed and blotted against specific antibodies.",
    "ncbi_link": "PPM1G: 5496"
  },
  {
    "caption": "(G) Cells transfected with vector, SFB-PR130 and SFB-B56δ and levels of pS641 α-catenin was detected using western blotting.",
    "ncbi_link": "PR130: 5523
B56δ: 5528"
  },
  {
    "caption": "(H) 293T Cells transfected with either empty vector, full length B56δ or indicated mutants were lysed and the levels of phosphorylated α-catenin was determined using pS641 α-catenin specific antibody.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(I) Cells treated with control shRNA and B56δ specific shRNAs were lysed and the levels of phosphorylated α-catenin was determined using pS641 α-catenin specific antibody.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "Cells were transduced with shRNAs as indicated and the effect of (J) B56δ expression on α-Catenin phosphorylation was assessed.",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": ", K) Cells were transduced with shRNAs as indicated and the effect of PPM1G expression on α-Catenin phosphorylation was assessed.",
    "ncbi_link": "PPM1G: 5496"
  },
  {
    "caption": "(L) SFB-PPM1G and SFB-PPM1G ΔNLS were transfected in both control shRNA and B56δ shRNA transduced cells. Lysates were pulled down using streptavidin beads and interaction with α-catenin was detected by western blotting using α-catenin antibody.",
    "ncbi_link": "PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(M) Control shRNA and B56δ shRNA cells were transfected with vector, MYC-PPM1G and MYC-PPM1G ΔNLS in indicated combination and pS641 α-catenin levels were determined using western blotting.",
    "ncbi_link": "MYC: 
PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(C) Control, PPM1G and B56δ shRNA transduced cells were transfected with SFB-α-catenin. Cell lysates were pulled down using streptavidin beads and interaction with β-catenin was determined by western blotting.",
    "ncbi_link": "α-catenin: 1495
PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(D) F-Actin in control and PPM1G depleted cells was stained using rhodamine labelled Phalloidin and the cytoskeleton arrangement was detected by using confocal microscope. Scale bars, 20 μm.",
    "ncbi_link": "PPM1G: 5496"
  },
  {
    "caption": "E) Localization of α-catenin and β-catenin in control shRNA cells or B56δ depleted cells with or without expression of SFB-PPM1G and SFB-PPM1G ΔNLS was detected by imaging with confocal microscope after staining with specific antibodies. Representative images are shown, Scale bars, 10 μm. (F) Quantification of plasma membrane (PM) to cytoplasmic ratio of α-catenin intensity per each cell from figure 4F was plotted (n=30 cells). Error bars indicate SD. ***p < 0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(A, B) MDA-MB-231 cells were transfected with vector control, PPM1G wild type, catalytically inactive PPM1G D496A mutant or α-Catenin and transwell migration assay was performed. Phase contrast microscopic images (A) were taken after staining the migrated cells with crystal violet and (B) Quantification data for migrated cells per field (derived from average of 3 different fields) from three independent experiments is shown. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "α-Catenin: 1495
PPM1G: 5496"
  },
  {
    "caption": "(C, D) MCF-7 cells were transfected with SFB-vector, SFB-B56δ or indicated mutants and transwell migration assay was performed. Phase contrast microscopic images (C) were taken after staining the migrated cells with crystal violet and (D) Quantification data for migrated cells per field (derived from average of 3 different fields) from three independent experiments is shown. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "B56δ: 5528"
  },
  {
    "caption": "(E, F) SFB-B56δ was expressed in control shRNA and PPM1G shRNA transduced MCF7 cells. Representative images from transwell migration assay (E) are shown and (F) quantified data for migrated cells per field from three independent experiments was plotted. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(G, H) SFB-PPM1G was expressed in control shRNA and B56δ shRNA transduced MCF7 cells. Representative images from transwell migration assay (G) are shown and (H) quantified data for migrated cells per field from three independent experiments was plotted. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(I, J) Control shRNA and B56δ shRNA transduced MCF7 cells were transfected with MYC-PPM1G and MYC-PPM1G ΔNLS. Representative images from transwell migration assay (I) performed with these cells are shown and (J) quantified data for migrated cells from three independent experiments per field was plotted. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "MYC: 
PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "(K, L) SFB-tagged α-catenin S641A and S641D mutants were expressed in PPM1G shRNA and B56δ shRNA transduced MCF7 cells as shown. Representative images from transwell migration assay (K) performed with these cells are shown and (L) quantified data for migrated cells per field from three independent experiments was plotted. Error bars indicate standard deviation (n=3), ***p<0.001 (one-way ANOVA, post hoc test: Bonferroni's multiple comparison test).",
    "ncbi_link": "α-catenin: 1495
PPM1G: 5496
B56δ: 5528"
  },
  {
    "caption": "A Actin expression levels shown by western blotting for strains expressing S. cerevisiae's actin protein from various coding sequences, with tubulin (Tub1p) as a loading control. B Quantification of actin expression levels, showing a decrease when more silent mutations are present. Data are presented as mean +/- SD (n = 4 for Sc, n = 8 for ScNI; n = 12 for Sc[Ca], Sc[Sp] and Sc[At]; 2 biological replicates with n/2 technical replicates each). *P<0.05 (Brown-Forsythe and Welch ANOVA tests, with Dunnett's T3 multiple comparisons tests).",
    "ncbi_link": "actin: 850504"
  },
  {
    "caption": "F In vivo actin network deviation indexes, defined to evaluate the patch-cable balance compared to S. cerevisiae haploid cells (value is 0 in S. cerevisiae's cells, 1 when cells contain only actin patches and -1 when cells contain only cables). Data are presented as mean +/- SD (n = 30 for all conditions). ***P<0.001 (Brown-Forsythe and Welch ANOVA tests, with Dunnett's T3 multiple comparisons tests).",
    "ncbi_link": "actin: 850504"
  },
  {
    "caption": "E Phalloidin staining of F-actin organization. Images are maximum intensity projections of 3D stacks and contrasts were adapted due to the fact that phalloidin labeling had a very different efficiency depending on the actin ortholog expressed. Micrographs of Sc and Sc_NI cells are reproduced from Fig 2E. Scale bar: 3 µm.",
    "ncbi_link": "actin: 850504"
  },
  {
    "caption": "I Effect of CK-666 (75 µM) on the organization of the actin cytoskeleton. Cells were stained with phalloidin after 30 min incubation with CK-666. Images are maximum intensity projections of 3D stacks. Scale bar: 3 µm J Quantification of actin patch resistance to CK-666 treatment. Bar graphs represent the percentage of cells with a given number of visible actin patches after CK-666 treatment. (n = 41 for ScNI, 55 for N2, 31 for Ca, 41 for Op, 55 for Hs).",
    "ncbi_link": "actin: 850504"
  },
  {
    "caption": "The intestine-specific RNAi against irx-1 reduces the Smurf phenotype at day 8 of adulthood. Mean ± SD. Scale bar: 100 μm. Unpaired t-test, two-tailed. More than 30 worms analysed in each of the three biological replicates.",
    "ncbi_link": "irx-1: 172789"
  },
  {
    "caption": ", C The intestine-specific RNAi against irx-1 reduces the Smurf phenotype at day 8 of adulthood. Mean ± SD. Scale bar: 100 μm. Unpaired t-test, two-tailed. More than 30 worms analysed in each of the three biological replicates.",
    "ncbi_link": "irx-1: 172789"
  },
  {
    "caption": "B, C The BWM-specific RNAi against myrf-2 improves sarcomere in the worms at day 8 of adulthood. Arrowheads and arrows respectively denote the gaps of myofilaments and the disorganised myofilaments with GFP aggregations. Scale Bar: 10 μm. Mean ± SD. Unpaired t-test, two-tailed. n>=50.",
    "ncbi_link": "GFP: 
myrf-2: 181229"
  },
  {
    "caption": "D, E Suppressing myrf-2 in BWM increases worms' motility at day 5 of adulthood. The tracks were from worms' movement in 30 sec (D). The speed of worm movement was measured by the ratio of track length versus body length (E). Mean ± SD. n>=120. Unpaired t-test, two-tailed.",
    "ncbi_link": "myrf-2: 181229"
  },
  {
    "caption": "Analysis of these Mtw1 mutants in vivo using the anchor-away technique. Mtw1-FRB strains containing RPL13-FKBP12 for cytoplasmic anchoring and additionally harboring the indicated rescue alleles were plated in serial dilution on YEPD or YEPD + Rapamycin plates incubated at 30 °C.",
    "ncbi_link": "Mtw1: 851197"
  },
  {
    "caption": "Tetrad analysis of Mtw1-wt or mutants. Surviving spores in which the Mtw1-wt or mutant rescue construct was the only source of Mtw1 are indicated in pink circles.",
    "ncbi_link": "Mtw1: 851197"
  },
  {
    "caption": "Western blotting confirming the expression of Mtw1-6x-Flag wt or mutant proteins in the Mtw1-FRB strain background.",
    "ncbi_link": "Mtw1: 851197"
  },
  {
    "caption": "Analysis of Ame1 N-terminal deletion and swap mutant using the anchor-away technique. Ame1-FRB strains containing RPL13-FKBP12 for ribosome anchoring and additionally harboring the indicated rescue alleles were plated in serial dilution on YEPD or YEPD + Rapamycin plates incubated at 30 °C.",
    "ncbi_link": "Ame1: 852512"
  },
  {
    "caption": "Tetrad dissection of strains where one endogenous copy of Ame1 was replaced with the indicated construct.",
    "ncbi_link": "Ame1: 852512"
  },
  {
    "caption": "Analysis of Mif2 N-terminal and swap mutant using the anchor-away technique as for (B). Phenotypes of the indicated Mif2 constructs were observed in an otherwise wild-type or ctf19∆ background.",
    "ncbi_link": "ctf19: 856089
Mif2: 853773"
  },
  {
    "caption": "Western blotting showing 6xFlag tagged Mif2 expression levels of strains from (G).",
    "ncbi_link": "Mif2: 853773"
  },
  {
    "caption": "Western blotting of elution fractions from an SEC experiment of Mif2-wt or Mif2Ame1-N swap in the absence (upper panel) or presence (lower panel) of Mtw1c.",
    "ncbi_link": "Mif2: 853773"
  },
  {
    "caption": "Analytical SEC chromatograms and corresponding Coomassie stained SDS-PAGE gels of Mif2-wt or Mif2-∆sigAT and MN alone and in combination at 10 µM concentration. All combinations were incubated for 1 h at 4°C prior to the run. MN (blue), Mif2 (red), combination (green). Note that the same MN elution profile and SDS-PAGE (upper panel) is displayed in both sets to improve clarity. Dashed boxes highlighting corresponding fractions were included to improve comparability.",
    "ncbi_link": "Mif2: 853773"
  },
  {
    "caption": "Phenotypic analysis of Mif2 mutants using a galactose inducible overexpression system. Strains harboring the indicated Mif2 expression constructs on pESC plasmids were plated in serial dilution on doHIS-Glucose or doHIS-Raffinose/Galactose plates and incubated at 30 °C.",
    "ncbi_link": "Mif2: 853773"
  },
  {
    "caption": "Serial dilution assay of chromosomally integrated Mif2 variants under the control of the pGAL promoter. Strains were plated on YEP-Glucose and YEP-Raffinose/Galactose plates.",
    "ncbi_link": "GAL: 852308
Mif2: 853773"
  },
  {
    "caption": "Microscopic analysis of kinetochores in Mif2 overexpressing cells visualizing Mtw1-GFP and Spc42-mCherry. Images of representative large budded cells after 16h in Galactose are shown. One kinetochore cluster is enlarged in the white box for each strain. Scale bar represents 5 µm. Brightfield images show the morphology of the corresponding yeast cell. Only large budded cells were included in the analysis. Quantification of (D) in which large budded cells were classified according to their Mtw1-GFP signal into the four indicated groups. A total of 100 cells was quantified for every strain. Mean values of the three indicated groups were calculated and plotted in a bar chart. Error bars indicate the SEM of 2 independent experiments.",
    "ncbi_link": "GFP: 
mCherry: 
Mif2: 853773
Mtw1: 851197
Spc42: 853824"
  },
  {
    "caption": "Phenotypic analysis of Mif2-∆sigAT mutant using the same galactose inducible overexpression system as in (A). Strains harboring the indicated Mif2 expression constructs on pESC plasmids were plated in serial dilution on doHIS-Glucose or doHIS-Raffinose/Galactose plates and incubated at 30 °C.",
    "ncbi_link": "Mif2: 853773"
  },
  {
    "caption": "(C) The E141A mutation abolishes the ADP-ribosylation of H2AX. Empty vector (EV), wild type (WT) or the E141A mutant (E141A) of H2AX was expressed in U2OS H2AX knockout cells that were treated with H2O2. ADP-ribosylated proteins were IPed with anti-ADPR antibody. ADP-ribosylated H2AX was examined by Western blotting using anti-H2AX antibody.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(E) PARP1, but not PARP2, mediates the ADP-ribosylation on H2AX. Wild type (WT) cells, PARP1-null cells or PARP2-null cells were treated with H2O2.",
    "ncbi_link": "PARP1: 142
PARP2: 10038"
  },
  {
    "caption": "(A) U2OS cells (WT) and U2OS H2AX knockout cells reconstituted with empty vector (H2AX KO+EV), wild type H2AX (H2AX KO+WT), or the E141A mutant H2AX (E141A) were treated with H2O2 or MMS. Cell viability was measured after 24 hours using MTT assay. Values are mean ± SD of three assays.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(B) U2OS cells (WT) and U2OS H2AX knockout cells reconstituted with empty vector (H2AX KO+EV), wild type H2AX (H2AX KO+WT), or the E141A mutant (E141A) H2AX were treated with H2O2 (2 mM in PBS, 5 minutes) or MMS (1 mM in medium, 30 minutes), subsequently; the cells were cultured in fresh DMEM medium for 2 weeks. The numbers of colony formation were counted. Values are mean ± SD of three assays.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(C) Damaged bases repair are suppressed in U2OS cells expressing the E141A mutant (E141A). U2OS cells (WT) and U2OS H2AX knockout cells reconstituted with wild type H2AX (H2AX KO+WT), or the E141A mutant H2AX (E141A) were treated with H2O2 (2 mM in PBS, 5 minutes) or MMS (1 mM in medium, 30 minutes) and harvested at the indicated recovery time points. Then FPG-modified comet assay was performed. NT: no treatment. Representative comet tails were shown. The olive tail moments (OTM) were summarized from at least 50 cells in each experiment. Values are mean ± SD of three assays.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(D) DNA replication in U2OS cells expressing the E141A mutant (E141A) is suppressed. Cells were treated with H2O2 (2 mM in PBS, 5 minutes), MMS (1 mM in medium, 30 minutes) or mock (PBS, 30 minutes), followed by BrdU incorporation (30 μM in medium, 30 minutes). Representative images show BrdU-positive cells in cells expressing WT H2AX or E141A following genotoxic stress. Nuclei were stained with DAPI (blue). The bottom panel histogram shows the percentage of BrdU incorporation in each sample, Values are mean ± SD of three assays.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(A) ADP-ribosylation mediates the recruitment of Neil3. GFP-Neil3 was expressed in U2OS cells, and cells were treated with olaparib (1 µM, 1 hour) or mock (0.1 % DMSO in medium, 1 hour). Following laser microirradiation treatment, the recruitment of Neil3 was examined with live-cell imaging at the indicated time points (left panel). The laser stripe is indicated with yellow arrowheads. The relocation kinetics is shown in the right panel. Data represents mean ± SD from three biologically independent experiments (right panel). At least 20 cells were included in each experiment.",
    "ncbi_link": "GFP: 
Neil3: 55247"
  },
  {
    "caption": "(B) The GRFs of Neil3 alone is sufficient to be recruited to the sites of DNA damage. Truncated mutants of Neil3 were generated and fused with a GFP tag. Following laser microirradiation treatment, the recruitment of truncated mutants Neil3 were examined with live-cell imaging at the indicated time points (left panel). The laser stripe is indicated with yellow arrowheads. The relocation kinetics is shown in the right panel. Data represents mean ± SD from three biologically independent experiments (right panel). At least 20 cells were included in each experiment.",
    "ncbi_link": "Neil3: 55247"
  },
  {
    "caption": "(C) PARP inhibitor treatment (olaparib: 1 µM, 1 hour) or lack of PARP1 suppresses the relocation of the GRFs of Neil3 to the DNA lesions. The laser stripe is indicated with yellow arrowheads. The relocation kinetics is shown in the right panel. Data represents mean ± SD from three biologically independent experiments (right panel). At least 20 cells were included in each experiment.",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "(B) Tandem co-immunoprecipitation and Western blotting assays demonstrate that Neil3 interacts with ADP-ribosylated H2AX but not the E141A mutant H2AX.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(E,F) The relocation kinetic of full-length Neil3 or the GRFs of Neil3 to DNA lesions was analyzed. GFP-tagged full length Neil3 or the GRFs of Neil3 was expressed in the indicated cells, and relocation kinetics was monitored in a time course following laser microirradiation (left panel). The laser stripe is indicated with yellow arrowheads. The relocation kinetics is shown in the right panel. Data represent mean ± SD from three biologically independent experiments (right panel). At least 20 cells were included in each experiment.",
    "ncbi_link": "GFP: 
Neil3: 55247"
  },
  {
    "caption": "(G,H) The recruitment of full-length Neil3 or the GRFs of Neil3 to the KR-induced oxidative lesions is mediated by H2AX ADP-ribosylation (left panel). Scale bars, 2 μm. The foci were indicated with white arrowheads. Scale bars, 0.5 μm. Right panel: the percentage of Neil3 or GRFs Neil3 foci co-localized with KR was quantified. Mean value with SD is from 20 cells.",
    "ncbi_link": "H2AX: 3014
Neil3: 55247"
  },
  {
    "caption": "(B) The effect of H2AX E141 ADP-ribosylation on γH2AX following oxidative stress. γH2AX or H2AX was detected using Western blotting and immunostaining assays. The intensity of γH2AX levels were examined by Western blotting normalized by β-actin and averaged. Values are mean ± SD of three assays. P-values were calculated using Student's t-test. **P < 0.01 (left panel). The number of γH2AX foci examined in immunostaining assay was counted by Image J software and graphed by GraphPad Prism 8.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(C) The intensity of γH2AX is increased in cell expressing the E141A mutant following KillerRed-induced oxidative DNA lesions (left panel). Scale bar, 2 μm. The foci were indicated with white arrowheads. Scale bar, 0.5 μm. Right panel: the relative intensity of γH2AX at the site of tetR (intensity of γH2AX at the site of tetR/intensity of γH2AX area away from tetR) was quantified. Mean value with SD is the relative intensity of γH2AX in 20 cells.",
    "ncbi_link": "H2AX: 3014"
  },
  {
    "caption": "(E) The recruitment of Neil3/MDC1 chimera but not wild type Neil3 to the KR-induced oxidative lesions in cells expressing the E141A mutant (left panel). Neil3/MDC1 chimera: replaced the GRFs of Neil3 with the tandem BRCT domains of MDC1. Scale bar, 2 μm. The foci were indicated with white arrowheads. Right panel: The percentage of detected protein foci co-localized with KR was quantified. Mean value with SD is from 20 cells.",
    "ncbi_link": "MDC1: 9656
Neil3: 55247"
  },
  {
    "caption": "(F) AP sites were measured in cells expressing the E141A mutant or the Neil3/MDC1 chimera, according to the standard curve. Values are mean ± SD of three assays.",
    "ncbi_link": "MDC1: 9656
Neil3: 55247"
  },
  {
    "caption": "(G) DNA replication of U2OS cells expression with individual wild type (WT), the H2AX KO + WT, the E141A mutant (E141A) or the Neil3/MDC1 Chimera (Chimera) were analyzed by BrdU incorporation following treatment with H2O2, MMS or mock (PBS). Represented images are shown in the left panel. The graph shows percentages of BrdU-positive cells expressing WT, E141A or Chimera (right panel).",
    "ncbi_link": "H2AX: 3014
MDC1: 9656
Neil3: 55247"
  },
  {
    "caption": "A, B. The recruitment of the mCherry fused p62 derived sensor AS3_p62 to the autophagosomes positive for overexpressed EGFP-LC3B (A) or endogenous LC3B (B) visualized by immunofluorescence upon autophagy induction for 3h by KU + Baf treatment.",
    "ncbi_link": "LC3B: 81631"
  },
  {
    "caption": "C. Recruitment of AS3_p62 in Atg5+/+ or Atg5-/- MEFs to endogenous Lc3b.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "D. FACS based mitophagy flux analysis performed in HeLa cell line stably expressing HA-Parkin, mt-mKeima, and a GFP fusion of the indicated sensor. Cells were treated with OAQ (oligomycin, antimycin, Q-VD) for indicated times and analyzed by FACS for lysosomal-positive mt-mKeima (561nm). The average of three independent experiments is presented. Representative FACS data from experiments (GFP control and AS3_67) are shown in the lower panels. Error bars indicate standard deviation. Significance calculation: 2-way anova of one-way anova. n.s.= not significant. *** indicates p-value of 0.0001.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "TF's target genes and GAPDH mRNA levels were analyzed by real-time qPCR. Results are expressed as relative mRNA expression levels.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "TEAD activity was analyzed in HeLa cells co-transfected with a renilla plasmid as a luciferase reporter plasmid controlled by the TEAD-responsive promoter, and with a renilla plasmid as a gene reporter; HeLa cells were cultured on 1 and 50 kPa (n = 3, t-test ***p<0.01) or treated with blebbistatin and blebbistatin + AP (n = 6; t-test *p<0.5).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "Quantifications of YAP activity (nucleo-cytoplasmic ratio) and p-Jun Ser63 nuclear intensity in cells depleted or not for SUN1 and SUN2.",
    "ncbi_link": "SUN1: 23353
SUN2: 25777"
  },
  {
    "caption": "Representative cells stained for p-Jun Ser63 (magenta) and for DNA (cyan) in Ctrl, Blebb and Blebb + AP conditions for cells depleted or not for lamin-A/C. Scale bar = 10 µm. Corresponding quantification of p-Jun Ser63 nuclear intensity.",
    "ncbi_link": "lamin-A/C: 4000"
  },
  {
    "caption": "in situ myeloid  specific MYDGF  overexpression in bone marrow was performed on CKO mice  aged 9 months. Micro-CT  analysis and histomorphometric analysis of distal  femora  were performed after 3 months intervention. H Representative images of H&E in distal femora, scale bar, 100 µm. I Quantification of number for  osteoblasts  in distal femora  (n=6). J Representative images of TRAP staining  in distal  femora, scale bar, 50µm K Quantification of number for osteoclasts in distal femora (n=6). L Representative images of calcein double-labeling, scale bar, 50μm. M Quantification of bone formation rate per  bone surface (BFR/BS) (n=6). Data information: Results are shown as mean ±SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t test).",
    "ncbi_link": "MYDGF: 28106"
  },
  {
    "caption": "Bone  defects models were conducted on young (3-month-old) and aged (18-month-old) mice, AAV-GFP or AAV-MYDGF  intra-marrow injection once 2 weeks before bone defects surgery on young and aged mice, and the defects area was analyzed after 2 weeks (n=10, there were 10 mice in each group, and 5 mice in each group were selected for detection at the end of the experiment). C, D Quantitative micro-CT  analysis of BMD (C) and BV/TV (D) of the regenerated bone in calvarial  defects (n=5). Data information: Results are shown as mean ± SEM, *P<0.05, **P<0.01, ***P<0.001 (Student's t test).",
    "ncbi_link": "GFP: 
MYDGF: 28106"
  },
  {
    "caption": "Bone  defects models were conducted on young (3-month-old) and aged (18-month-old)  mice, AAV-GFP or AAV-MYDGF intra-marrow injection once 2 weeks before bone  defects surgery on young and aged mice, and the defects area was analyzed after 2 weeks (n=10, there were 10 mice in each group, and 5 mice in each group were selected for detection at the end of the experiment). I, J Quantitative micro-CT  analysis of BMD (I) and BV/TV (J) of the regenerated  bone in calvarial  defects (n=5). Data information: Results are shown as mean ± SEM, *P<0.05, **P<0.01, ***P<0.001 (Student's t test).",
    "ncbi_link": "GFP: 
MYDGF: 28106"
  },
  {
    "caption": "OVX mice and 18-month-old male mice  serve as the model of  osteoporosis, AAV-MYDGF or AAV-GFP were injected into bone marrow cavity every 3 weeks for 12 weeks (n=10, there were 10 mice in each group, and 6 mice in each group were selected for detection at the end of the experiment). Micro-CT  reconstruction, H&E staining of trabecular bone from distal femurs in Sham +GFP, OVX  +GFP and OVX + MYDGF groups (n=6). Representative images of micro-CT reconstruction, scale bar, 2mm (A). Representative images of H&E staining in distal  femora, scale bar, 500μm for upper panel,100μm for lower panel (D).",
    "ncbi_link": "GFP: 
MYDGF: 28106"
  },
  {
    "caption": "OVX mice and 18-month-old male mice  serve as the model of osteoporosis, AAV-MYDGF or AAV-GFP  were injected into bone marrow cavity every 3 weeks for 12 weeks (n=10, there were 10 mice in each group, and 6 mice in each group were selected for detection at the end of the experiment). H&E staining  of  trabecular bone from distal femurs  in aged mice with AAV-GFP or AAV-MYDGF  (n=6). Representative images of H&E staining in distal femora, scale bar, 500μm for upper panel,100μm for lower panel (J).",
    "ncbi_link": "GFP: 
MYDGF: 28106"
  },
  {
    "caption": "A  qRT-PCR analysis for Nfatc1,  Ctsk, c-Fos, Mmp9  and Acp5 mRNA expression in BMMs cultured in osteoclastogenesis induction medium for 48 hours. Data information: Results are shown as mean ± SEM. *P＜0.05, **P＜0.01, ***P＜0.001 (Student's t test).",
    "ncbi_link": "Acp5: 11433
Ctsk: 13038
c-Fos: 14281
Mmp9: 17395
Nfatc1: 18018"
  },
  {
    "caption": "M BMMs were treated with control, RANKL or MG132 for osteoclastogenesis, then with or without rMYDGF for 24 hours. IgG, P65 and histone antibodies were used to  ChIP and RT-PCR was performed to determine Nfatc1 promoters. Data information: Results are shown as mean ± SEM. *P＜0.05, **P＜0.01, ***P＜0.001 (Student's t test).",
    "ncbi_link": "Nfatc1: 18018"
  },
  {
    "caption": "H The mRNA levels of Runx2 in BMSCs cultured in osteogenesis medium induction for 48 hours with indicated interventions. I, J Quantitative analysis of ALP  activity (I) and calcium mineralization (J) in BMSCs cultured in osteogenesis medium induction for 48 hours with indicated intervention. Data information: Results are shown as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001(Student's t test).",
    "ncbi_link": "Runx2: 12393"
  },
  {
    "caption": "(A and B) Immunoblot of 9-mo-old quadricepsmuscle lysates from control (cont) or VCP-WT, -RH9, or -RH12 mutant transgenic lines with p62 (A) or LC3 (B) antibodies. Note the increase in p62 and LC3II isoforms in mutant animals. Densitometric quantification is from more than six 9-mo-old animals/group. LC3 and p62 levels are normalized to loading control. Error bars represent the standard error from six independent experiments. **, P < 0.001. AU, arbitrary unit.",
    "ncbi_link": "VCP: 269523"
  },
  {
    "caption": "(C) p62 immunostaining of tibialis anterior (TA) or quadriceps (Quad) muscle from 9-mo-old control, VCP-WT, or one of two VCP-RH transgenic lines (RH9 or RH12). Note accumulations of p62 in the middle of myofibers or along subsarcolemmal regions.",
    "ncbi_link": "VCP: 269523"
  },
  {
    "caption": "(D) Histochemistry and immunohistochemistry of quadriceps muscle from VCP-RH-expressing transgenic mice. Hematoxylin and eosin (H&E) staining of a 15-mo-old animal with an RV, p62 immunostaining of an RV from a 12-mo-old animal, LC3 immunostaining of an RV, and subsarcolemmal accumulations of LC3 from a 12-mo-old animal. The bracket highlights one LC3-positive myofiber. A single muscle fiber is outlined in white. (C and D) Arrows denote vacuoles or accumulations of p62 or LC3. Bars, 30 µm.",
    "ncbi_link": "VCP: 269523"
  },
  {
    "caption": "(A) Lysates from scrambled siRNA or VCP-targeted siRNA-treated U20S cells immunoblotted with antibodies to VCP, LC3, p62, or α-tubulin. Densitometric analysis is graphically represented from four independent experiments. LC3 and p62 levels are normalized to loading control.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(B) Fluorescent microscopy images of siRNA scrambled control (Scr) or VCP-targeted siRNA KD cells expressing GFP-LC3. Basal numbers of GFP-LC3 puncta/cell were counted.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(C) Lysates from control or myc-tagged VCP-WT, ATPase-inactive VCP-EQ, or one of two IBMPFD mutants, VCP-RH or -AE, expressed for 16 h from stably transfected tetracycline-inducible U20S cells and immunoblotted with antibodies to myc, LC3, p62, or α-tubulin. Densitometric analysis is graphically represented from four independent experiments. LC3 and p62 levels are normalized to loading control. Note the increase in LC3II and p62 in VCP siRNA KD and mutant-expressing cells.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(D) Fluorescent microscopy images of tetracycline-inducible U20S cells expressing GFP-LC3 treated with and without Baf for 4 h (DMSO control [left] or Baf+ [right]). Cells are control U20S cells and VCP-WT, -RH, -AE, and -EQ. (E) The number of GFP-LC3 puncta/cell was counted for control U20S and VCP-WT, -EQ, -RH, and -AE with and without Baf for 4 h (DMSO or Baf). Note the increase in basal GFP-LC3 puncta in mutant-expressing cells. (A-C and E) Error bars represent the standard error from four independent experiments. *, P < 0.01; and **, P < 0.001. Bars, 25 µm.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(A) Epifluorescent images for GFP and mRFP in U20S or VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells transfected with mRFP-GFP-LC3 (tfLC3) and treated with rapamycin for 2 h to induce autolysosome formation. (B) siRNA control (Scr) or VCP-KD- or Baf-treated control U20S cells transfected with tfLC3 and treated with rapamycin for 2 h to induce autolysosome formation. (A and B) Open arrows denote autophagosomes (both GFP and mRFP fluorescence), whereas closed arrows highlight autolysosomes (mRFP only fluorescence). (C) The graph represents Pearson's coefficient of GFP and mRFP colocalization from 10 independent fields of cells in two different experiments. Error bars represent the standard error from 20 fields in two independent experiments. *, P < 0.001.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(D) Lysates from U20S or tetracycline-inducible VCP-WT, -RH, or -AE cells treated with vehicle or Baf for 4 h and immunoblotted for LC3 and α-tubulin. Note that Baf treatment does not increase the LC3II levels in IBMPFD mutant (RH and AE)-expressing cells. Bars, 15 µm.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(A) Lysates from siRNA-treated U20S cells (scramble control [Scr] or VCP siRNA KD) after autophagic induction via nutrient deprivation for 0, 2, or 4 h and immunoblotting for LC3 and α-tubulin. LC3II degrades over time in control but not in KD cells. One of two experiments is shown.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(B) Lysates from U20S or tetracycline-inducible VCP-WT, -EQ, -RH, or -AE cells after autophagic induction via nutrient deprivation for 0, 2, 4, or 6 h and immunoblotting for LC3 and α-tubulin. LC3II degrades in control and VCP-WT but degrades less efficiently in mutant (EQ, RH, or AE)-expressing cells. (C) Graphical representation of densitometric evaluation of LC3II and α-tubulin at each time point from three independent experiments.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(A) Epifluorescent images for GFP-LC3 (LC3) and LTR of VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells transfected with GFP-LC3 and treated with rapamycin for 2 h to induce autolysosome formation. Open arrows highlight autolysosomes (GFP and LTR colocalized), and closed arrows show autophagosomes (GFP only). (B) Pearson's coefficient of GFP and LTR colocalization from 10 independent fields of cells in two different experiments.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(C) Epifluorescent images for GFP-LC3 and endogenous Lamp1 immunohistochemistry of U20S, VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells or U20S cells cotreated with Baf transfected with GFP-LC3 and treated with rapamycin for 2 h to induce autolysosome formation. Arrows highlight autolysosomes (GFP and Lamp1 colocalized). (A and C) The boxed regions in the merge field are enlarged in the adjacent panels. (D) Pearson's coefficient of GFP and Lamp1 colocalization from 10 independent fields of cells in two different experiments. (B and D) Error bars represent the standard error from 20 fields in two independent experiments. *, P < 0.001.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(E) Electron microscopy of tetracycline-inducible control or VCP-WT-, VCP-RH-, or VCP-AE-expressing U20S cells induced for 16 h and then treated with rapamycin for 2 h. Note the accumulation of autophagic structures in the mutant-expressing cell lines. Arrows denote autophagic structures.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(A) Immunofluorescence images of quadriceps muscle using p62 and Lamp1 or -2 antibodies. Quadriceps section from a 9-mo-oldVCP-WT mouse, age-matched VCP-RH transgenic, 12-mo-oldVCP-RH transgenic, and IBMPFD patientmuscle biopsy are shown. Open arrows highlight p62 and Lamp1/2 colocalization, and closed arrows show regions of only p62immunofluorescence. Single myofibers containing RVs are outlined in the merge panels.",
    "ncbi_link": "VCP: 7415
VCP: 269523"
  },
  {
    "caption": "(B and C) Transmission electron microscopy of tibialis anterior muscle from one of two independent lines (B shows RH12, and C shows RH9 lines) of 12-mo-old VCP-RH-expressing transgenic mice. Note the large vacuolated structures that are perinuclear or subsarcolemmal. Bars: (A) 30 µm; (B and C) 500 nm.",
    "ncbi_link": "VCP: 269523"
  },
  {
    "caption": "(A) Representative images using in vivo bioluminescence of control or IBMPFD mutant RH-expressing mice (RH12) 2 d after electroporation (baseline) or after 24 h of nutrient deprivation (starvation) of polyQ80 (Q80)- or polyQ19-luciferase (Q19) in the right and left tibialis anterior, respectively. The ratio of polyQ80-luciferase/polyQ19-luciferase is indicated below each image set. Values are in ×104 photons per second per square centimeter per steradian. (B) Box and whisker plot of the change (Δ) in the ratio of polyQ80-luciferase/polyQ19-luciferase activity in the left and right tibialis anterior muscle of control, VCP-WT, or one of two VCP-RH (RH12 or RH9) transgenic mouse lines after 24 h of starvation. The graph is representative of three animals per group. The p-value for RH12 was 0.05 and 0.06 when compared with control animals or VCP-WT transgenic. The p-value for RH9 was 0.03 when compared with either control or VCP-WT transgenic. The p-value was 0.01 and 0.02 when combined RH12 and RH9 animals were compared with control or VCP-WT groups, respectively. There was no statistical difference between control or VCP-WT groups.",
    "ncbi_link": "luciferase: 
VCP: 269523"
  },
  {
    "caption": "(A) Quantitation of mCherry-TDP-43 distribution (nuclear only or cytoplasmic) in control U20S, VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells, or control U20S cells treated with 10 µM Baf or 50 µM chloroquine (Chlq) for 4 h from 10 different fields from two independent experiments. Error bars represent the standard error from 20 fields in two independent experiments. *, P < 0.02 when compared with VCP-WT-expressing cells. (B) Epifluorescent images for mCherry-TDP-43 (red) and DAPI (blue) in control U20S, VCP-WT-, VCP-RH-, or VCP-AE-expressing cells, or control U20S cells treated with Baf or chloroquine for 4 h. Arrows denote cytosolic TDP-43 and perinuclear TDP-43 inclusions.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(C, top) Immunoblot for TDP-43, lamin A/C, and actin from nuclear or cytosolic lysate fractions of mCherry-TDP-43-transfected VCP-WT-, VCP-RH-, VCP-AE-, or VCP-EQ-expressing cells. Note the increase in cytosolic TDP-43 from IBMPFD mutant- and EQ-expressing cells. (bottom) Immunoblot for TDP-43, lamin A/C, and actin from nuclear or cytosolic lysate fractions of untreated U20S cells transfected with mCherry-TDP-43 or similarly transfected cells treated with 30 µg/ml (cq1) or 120 µg/ml (cq2) chloroquine diphosphate or 200 ng/ml Baf. Data are representative of three independent experiments. Bar, 15 µm.",
    "ncbi_link": "VCP: 269523
VCP: 7415"
  },
  {
    "caption": "(A) TDP-43 immunostaining of quadriceps skeletal muscle from 15-mo-old control (Cont) or VCP-WT, -RH9, or -RH12 transgenic mice. A single myofiber is outlined in white.",
    "ncbi_link": "VCP: 269523"
  },
  {
    "caption": "D. Analyses of Hog1 phosphorylation by immunoblotting with anti-phospho-p38 (Hog1-P) and anti-Hog1 (total Hog1) antibodies. Yeast strain KT219 was transformed with the indicated STE11 mutant gene carried by a single-copy plasmid that is expressed from the STE11 promoter: vec, vector; WT, wild-type; DDD, S281D/S285D/T286D. Cells were incubated with (+) or without (-) 1 M NaCl for 5 min.",
    "ncbi_link": "STE11: 851076"
  },
  {
    "caption": "D. Phos-tag band-shift analyses of Hog1 phosphorylation. The yeast strain KT234 carrying the single-copy expression plasmid YCplac22I'-Pbs2 S514D/T518D was stimulated with the indicated concentrations of NaCl for 5 min.",
    "ncbi_link": "Pbs2: 853313"
  },
  {
    "caption": "E. Comparison of the NaCl dose-responses of Hog1 activation by constitutively-active Ste11-Q301P and constitutively-active Pbs2-DD. Phos-tag band-shift assays were independently repeated three times, and the average values were plotted. Data information: (E) Error bars are SEM (n=3).",
    "ncbi_link": "Pbs2: 853313
Ste11: 851076"
  },
  {
    "caption": "C. Immunoblot analyses of Hog1 phosphorylation. The yeast strain KT235 was transformed with pRS416-FLAG-Hog1 (WT) or its indicated deletion derivatives. FLAG-Hog1 was immunoprecipitated (IP), and immunoblotted (IB) with anti-phospho-p38 (for Hog1-P; upper panel) or anti-FLAG (for total FLAG-Hog1; lower panel)",
    "ncbi_link": "FLAG: 
Hog1: 850803"
  },
  {
    "caption": "D-G. Phos-tag band-shift assay of Hog1 phosphorylation. Yeast strain (D-E) KT235 or (F-G) KT290 carrying the single-copy expression plasmid YCplac22I'-Pbs2 S514D/T518D was transformed with either pRS416-Hog1 (WT) or its indicated mutant derivatives, and was treated with the indicated concentrations of NaCl for 5 min. (D) and (F) show typical results, and (E) and (G) summarizes the averages of three independent experiments. Data information: (E, G Error bars are SEM (n=3).",
    "ncbi_link": "Hog1: 850803
Pbs2: 853313"
  },
  {
    "caption": "H. Phos-tag band-shift assay of Hog1 phosphorylation. The yeast strain FP4 was transformed with the single-copy expression plasmid pRS416-Hog1 (WT) or pRS416-Hog1-ΔL16, and was treated with the indicated concentrations of NaCl for 5 min. The averages of three independent experiments are shown. Data information: Error bars are SEM (n=3).",
    "ncbi_link": "Hog1: 850803"
  },
  {
    "caption": "A. Phos-tag band-shift analyses of osmostress-induced Hog1 phosphorylation. The yeast strain FP4 (hog1Δ) was transformed with the single-copy expression plasmid pRS416-Hog1-ΔL16, and was stimulated with the indicated concentrations of NaCl for 5 min. B. Averages of three independent experiments from A were plotted. Results for Hog1-WT (from Fig 1I) are included for comparison. Data information: Representative results from three independent experiments. Error bars are SEM (n=3).",
    "ncbi_link": "hog1: 850803
Hog1: 850803"
  },
  {
    "caption": "C-D. the yeast strain KT259 (ste11Δ hog1Δ) was used. Data information: Representative results from three independent experiments. Error bars are SEM (n=3).",
    "ncbi_link": "hog1: 850803
ste11: 851076"
  },
  {
    "caption": "E-F. the yeast strain KY523 (ssk2/22Δ hog1Δ) was used. Data information: Representative results from three independent experiments. Error bars are SEM (n=3).",
    "ncbi_link": "hog1: 850803
ssk2: 855765"
  },
  {
    "caption": "Detection of Pbs2 phosphorylation at S514 The yeast strains KT003 (pbs2Δ), KT005 (ste11Δ pbs2Δ), TM280 (ssk2/22Δ pbs2Δ) and KT043 (ste11Δ ssk2/22Δ pbs2Δ) were transformed with YCplac22I'-Pbs2-HA, and were treated with the indicated concentrations of NaCl for 5 min. Pbs2-HA was immunoprecipitated from cell extract, and phosphorylated Pbs2 was analyzed by (A) Phos-tag band-shift assay In (A), the positions of Pbs2-HA phosphorylated (S514-P) and unphosphorylated (S514-OH) at S514 are indicated.",
    "ncbi_link": "HA: 
pbs2: 853313
Pbs2: 853313
ssk2: 855765
ste11: 851076"
  },
  {
    "caption": "Detection of Pbs2 phosphorylation at T518. The yeast strains KT003 (pbs2Δ), KT005 (ste11Δ pbs2Δ), TM280 (ssk2/22Δ pbs2Δ) and KT043 (ste11Δ ssk2/22Δ pbs2Δ) were transformed with YCplac22I'-Pbs2-HA, and were treated with the indicated concentrations of NaCl for 5 min. Pbs2-HA was immunoprecipitated from cell extract, and phosphorylated Pbs2 was analyzed by (B) anti-phospho-T518 immunoblotting.",
    "ncbi_link": "HA: 
pbs2: 853313
Pbs2: 853313
ssk2: 855765
ste11: 851076"
  },
  {
    "caption": "C-F. NaCl dose-response analyses of Pbs2 phosphorylation. (C-D) KT005 (ste11Δ pbs2Δ) and (E-F) TM280 (ssk2/22Δ pbs2Δ) were transformed with YCplac22I'-Pbs2-HA, and were treated with the indicated concentrations of NaCl for 5 min. (C and E) S514 phosphorylation was analyzed using the Phos-tag band-shift assay. PC; Positive Control. (D and F) T518 phosphorylation was analyzed using anti-phospho-T518 immunoblotting. G-H. Average values of three independent experiments from (C-D) and (E-F), respectively, were plotted. AU, arbitrary unit. Data information: (C-F) Representative results from three independent experiments. (G-H) Error bars are SEM (n=3).",
    "ncbi_link": "HA: 
pbs2: 853313
Pbs2: 853313
ssk2: 855765
ste11: 851076"
  },
  {
    "caption": "I. Detection of di-phosphorylated Pbs2. KT005 (ste11Δ pbs2Δ) transformed with YCplac22I'-Pbs2-HA was treated with the indicated concentrations of NaCl for 5 min. Pbs2-HA was immunoprecipitated from cell extracts, and subjected to Phos-tag SDS-PAGE. Blots of these gels were probed with (upper panel) anti-phospho-T518 or (lower panel) anti-HA. J. Same as in (I), except that the yeast strain KT003 (pbs2Δ) was used. ",
    "ncbi_link": "HA: 
pbs2: 853313
Pbs2: 853313
ste11: 851076"
  },
  {
    "caption": "B. Phos-tag band-shift analyses of osmostress-induced Hog1 phosphorylation. KT005 (ste11Δ pbs2Δ) was transformed with YCplac22I'-Pbs2 -HA (WT) or its indicated mutant derivatives. Cells were stimulated with (+) or without (-) 0.6 M NaCl for 5 min.",
    "ncbi_link": "HA: 
pbs2: 853313
Pbs2: 853313
ste11: 851076"
  },
  {
    "caption": "C-F. Phos-tag band-shift analyses of Hog1 phosphorylation. KT291 (ste11Δ pbs2Δ hog1Δ) was transformed with (C and D) pRS416-Hog1 or (E and F) pRS416-Hog1-ΔL16, together with (C and E) YCplac22I'-Pbs2-S514A-HA or (D and F) YCplac22I'-Pbs2-T518A-HA. Cells were stimulated with the indicated concentrations of NaCl for 5 min. G-H. Average values of three independent experiments from (C and E) and (D and F), respectively, are plotted. Data information: (C-F) Representative results from three independent experiments. (G-H) Error bars are SEM (n=3).",
    "ncbi_link": "HA: 
hog1: 850803
Hog1: 850803
pbs2: 853313
Pbs2: 853313
ste11: 851076"
  },
  {
    "caption": "A Phos-tag band-shift assay of Hog1 phosphorylation. KT235 (ΔS/O/H/M ssk2/22Δ hog1Δ STE11-Q301P) was transformed with pRS416-Hog1 (WT) or its indicated mutant derivatives. Cell extracts were prepared from fresh cultures without applying osmostress. For each HOG1 mutant plasmid, three independent cultures were assayed. Data information: Error bars are SEM (n=3).",
    "ncbi_link": "HOG1: 850803
hog1: 850803
Hog1: 850803
ssk2: 855765
STE11: 851076"
  },
  {
    "caption": "B. the yeast strains KT260 (ssk2/22Δ ste11Δ hog1Δ), KT235 (ΔS/O/H/M ssk2/22Δ hog1Δ STE11-Q301P), and KT248 (ΔS/O/H/M ssk2/22Δ hog1Δ pbs2Δ) carrying YCplac22I'-Pbs2-DD, were used. Data information: Error bars are SEM (n=3).",
    "ncbi_link": "hog1: 850803
pbs2: 853313
Pbs2: 853313
ssk2: 855765
ste11: 851076
STE11: 851076"
  },
  {
    "caption": "C. KT250 (ΔS/O/H/M ssk2/22Δ hog1Δ STE11-WT) and KT235 (ΔS/O/H/M ssk2/22Δ hog1Δ STE11-Q301P) were transformed with pRS416-Hog1 (WT) or pRS416-Hog1-N149H D162G (N149H D162G) together with pRS414-8xCRE-lacZ. Expression of the Hog1 reporter gene 8xCRE-lacZ in the absence of osmostress was assayed. Data information: (C) Error bars are SEM (n=4).",
    "ncbi_link": "lacZ: 
CRE: 2777477
hog1: 850803
Hog1: 850803
ssk2: 855765
STE11: 851076"
  },
  {
    "caption": "D. KT248 (ΔS/O/H/M ssk2/22Δ hog1Δ pbs2Δ) was transformed with pRS416-Hog1 (WT) or its indicated mutant derivatives together with pRS414-8xCRE-lacZ. Expression of the Hog1 reporter gene 8xCRE-lacZ in the absence of osmostress was assayed. Data information: Error bars are SEM (n=3).",
    "ncbi_link": "lacZ: 
CRE: 2777477
hog1: 850803
Hog1: 850803
pbs2: 853313
ssk2: 855765"
  },
  {
    "caption": "E-F. Phos-tag band-shift assay of Hog1 phosphorylation. Yeast strains of the indicated genotypes (shown below the graph) were transformed with pRS416-Hog1 (WT) or its indicated mutant derivatives (shown inside the graph). Strain used: (E) FP4, KT259, KT260, KT292, and KY523; and (F) KY523, KT293, KT294, and KT295. N/H, N149H; D/G, D162G. Data information: Error bars are SEM (n=3).",
    "ncbi_link": "Hog1: 850803"
  },
  {
    "caption": "A. KT299 (MATa hkr1Δ msb2Δ ssk2/22Δ) was exposed to the indicated concentrations of α-factor for 15 min in the absence of osmostress. Phosphorylation of Fus3 and Kss1 was detected by immunoblotting.",
    "ncbi_link": "hkr1: 852030
msb2: 852897
ssk2: 855765"
  },
  {
    "caption": "B. KT299 (MATa ssk2/22Δ hkr1Δ msb2Δ) was exposed to the indicated concentrations of α-factor for 15 min in the presence or absence of 0.8 M NaCl, and Hog1 phosphorylation was determined using the Phos-tag band-shift assay. Data information: (B) Representative results from three independent experiments.",
    "ncbi_link": "hkr1: 852030
msb2: 852897
ssk2: 855765"
  },
  {
    "caption": "D. HM06-1 (MATa ΔS/O/H/M ssk2/22Δ) was exposed to the indicated concentrations (log scale) of α-factor for 15 min in the presence or absence of 1.0 M NaCl, and Hog1 phosphorylation was determined using the Phos-tag band-shift assay. Average values of three or more independent experiments were plotted. Data information: Error bars are SEM: (D), n=3 or more",
    "ncbi_link": "ssk2: 855765"
  },
  {
    "caption": "E. KT306 (MATa hkr1Δ msb2Δ ssk2/22Δ hog1Δ) was transformed with pRS416-Hog1 (WT) or pRS416-Hog1-N149H D162G (N/H D/G), and was exposed to 10 μM α-factor for the indicated time in the absence of osmostress, and Hog1 phosphorylation was determined using the Phos-tag band-shift assay. Average of three independent experiments are plotted. Data information: Error bars are SEM (E) n=3.",
    "ncbi_link": "hkr1: 852030
hog1: 850803
Hog1: 850803
msb2: 852897
ssk2: 855765"
  },
  {
    "caption": "G. Typical FRET (YFP/CFP ratio) images showing p38 activation. HeLa cells carrying the p38 reporter PerKy-p38 (Tomida et al., 2015) were stably transfected with an expression vector for the indicated p38α mutant proteins. FRET analysis was performed as described in Materials and Methods. H. Distribution of p38 activity in individual cells from sets (a) - (d) in (G). Data information: (G) Scale bars: 20 μm. (H) Statistics, Student's two-tailed t-test.",
    "ncbi_link": "p38α: "
  },
  {
    "caption": "A. An example of the time-course experiments for the osmostress-induced Hog1 phosphorylation. The yeast strain KY603-3 (ΔS/O/H/M ssk2/22Δ STE11-Q301P) was stimulated with 1.0 M NaCl for the indicated times, and the percentage of phosphorylated Hog1 (Hog1-P) was determined using a Phos-tag band-shift assay.",
    "ncbi_link": "ssk2: 855765
STE11: 851076"
  },
  {
    "caption": "Compilations of the time-courses of osmostress-induced Hog1 activation in (B) KY603-3 (ΔS/O/H/M ssk2/22Δ STE11-Q301P), For clarity, time-course curves are shown in two panels for lower and higher ranges of NaCl concentrations. Data information: For each data point, n=1 or more.",
    "ncbi_link": "ssk2: 855765
STE11: 851076"
  },
  {
    "caption": "Compilations of the time-courses of osmostress-induced Hog1 activation in (C) TM257 (ssk2/22Δ), and (D) TM142 (wild-type). For clarity, time-course curves are shown in two panels for lower and higher ranges of NaCl concentrations. The color chart below (D) indicates the concentrations of NaCl used. Data information: For each data point, n=1 or more.",
    "ncbi_link": "ssk2: 855765"
  },
  {
    "caption": "E. Effects of Hog1 kinase activity and osmostress-induced glycerol accumulation on the time-courses of Hog1 activation. Cells were stimulated with 0.4 M NaCl (left panel) or 1.6 M NaCl (right panel) for the indicated times, and the percentage of phosphorylated Hog1 was determined using Phos-tag band-shift assay. Strains used were: TM142 (WT), KT254 (gpd1Δ gpd2Δ stl1Δ), and TM232 (hog1Δ) carrying pRS416-HOG1-K52S K53N. K/S K/N, K52S K53N; gpd1/2, gpd1Δ gpd2Δ. Data information: (E) Error bars are SEM (n=3 or more).",
    "ncbi_link": "gpd1: 851539
gpd2: 854095
hog1: 850803
HOG1: 850803
stl1: 852149"
  },
  {
    "caption": "A Control animals (+/w; UAS-ralIR/+), n= 20, and those with salivary gland-specific knockdown of ral (fkh-GAL4/w; UAS-ralIR/+), n=20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.B Quantification of data from (A). Data are represented as means. Statistical significance was determined using a Chi-square test.C Control animals (+/w; UAS-ralS25N/+), n= 20, and those with salivary gland-specific expression of dominant-negative Ral (fkh-GAL4/w; UAS-ralS25N/+), n= 20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.D Quantification of data from (C). Data are represented as means. Statistical significance was determined using a Chi-square test.E Control animals (ral35d/+), n= 25, and ral hypomorph mutants (ral35d/Y), n= 23, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.F Quantification of data from (E). Data are represented as means. Statistical significance was determined using a Chi-square test.",
    "ncbi_link": "fkh: 43383
GAL4: 855828
ral: 31332
Ral: 31332"
  },
  {
    "caption": "G Control animals (+/w; UAS-rglIR/+), n= 19, and those with salivary gland-specific knockdown of rgl (fkh-GAL4/w; UAS-rglIR/+), n=20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.H Quantification of data from (G). Data are represented as means. Statistical significance was determined using a Chi-square test.",
    "ncbi_link": "fkh: 43383
GAL4: 855828
rgl: 44115"
  },
  {
    "caption": "A ral hypomorph mutants (ral35d/Y;; UAS-p35/+), n= 20, animals with salivary gland-specific expression of p35 (ral35d/+;; UAS-p35/fkh-GAL4), n= 21, and ral hypomorph mutants with salivary gland-specific expression of p35 (ral35d/Y;; UAS-p35/fkh-GAL4), n= 20, were analyzed by histology for the presence of salivary gland material (red dotted circles) 24 hours after puparium formation.B Quantification of data from (A). Data are represented as means. Statistical significance was determined using a Chi-square test comparing the percentages of gland fragments.",
    "ncbi_link": "p35: 
fkh: 43383
GAL4: 855828
ral: 31332"
  },
  {
    "caption": "C Salivary glands dissected from 0 hour after puparium formation control animals (+/w; UAS-ralIR/+) and those with salivary gland-specific knockdown of ral (fkh-GAL4/w; UAS-ralIR/+) and stained with cleaved Caspase-3 antibody (green) and DAPI (blue). Scale bars represent 20µm.D Salivary glands dissected from 13 hour after puparium formation control animals (+/w; UAS-ralIR/+) and those with salivary gland-specific knockdown of ral (fkh-GAL4/w; UAS-ralIR/+) and stained with cleaved Caspase-3 antibody (green) and DAPI (blue). Scale bars represent 20µm.E Quantification of data from (C and D). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "fkh: 43383
GAL4: 855828
ral: 31332"
  },
  {
    "caption": "A ral hypomorph mutants (ral35d/Y;; UAS-Atg6IR/+), n= 27, animals with salivary gland-specific expression of Atg6IR (ral35d/+;; UAS-Atg6IR/fkh-GAL4), n= 20, and ral hypomorph mutants with salivary gland-specific expression of Atg6IR (ral35d/Y;; UAS-Atg6IR/fkh-GAL4), n= 24, were analyzed by histology for the presence of salivary gland material (red dotted circles) 24 hours after puparium formation.B Quantification of data from (A). Data are represented as means. Statistical significance was determined using a Chi-square test.",
    "ncbi_link": "Atg6: 42850
fkh: 43383
GAL4: 855828
ral: 31332"
  },
  {
    "caption": "C Salivary glands dissected from 14 hours after puparium formation animals expressing mCherry-Atg8a in all cells, and ralIR specifically in GFP-marked clone cells (yw, hsflp/w; pmCherry-Atg8a/UAS-ralIR; act< FRT, cd2, FRT> GAL4, UAS-GFP/+) analyzed for mCherry-Atg8a puncta. GFP-marked clone ralIR-expressing cells contain a yellow asterisk. Scale bars represent 20µm.D Quantification of data from (C). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.E Salivary glands dissected from 14 hours after puparium formation animals that have ral loss of function (ralPG89) specifically in non-RFP cells, and that express GFP-Atg8a in all cells (yw, hs-Flp, FRT19A, Ubi-RFP/ ralPG89,FRT19A; pGFP-Atg8a) analyzed for GFP-Atg8a puncta. ralPG89 mutant cells are marked with a yellow asterisk. Scale bars represent 20µm.F Quantification of data from (E). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.G Salivary glands dissected from 14 hours after puparium formation animals that have ral loss of function (ralPG89) specifically in non-RFP cells (yw, hs-Flp, FRT19A, Ubi-RFP/ ralPG89,FRT19A) and are stained for Ref(2)p (green) and DAPI (blue). ralPG89 mutant cells are marked with a yellow asterisk. Scale bars represent 20µm.H Quantification of data from (G). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "Ubi: 
GAL4: 855828
ral: 31332"
  },
  {
    "caption": "I Fat bodies dissected from 4 hour starved animals that have ral loss of function (ralPG89) specifically in non-RFP cells, and that express GFP-Atg8a in all cells (yw, hs-Flp, FRT19A, Ubi-RFP/ ralPG89,FRT19A; pGFP-Atg8a) analyzed for GFP-Atg8a puncta. ralPG89 mutant cells are marked with a yellow asterisk. Scale bars represent 20µm.J Quantification of data from (I). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "Ubi: 
ral: 31332"
  },
  {
    "caption": "A, C, E, G, I Fat bodies dissected from 4 hour starved animals expressing mCherry-Atg8a in all cells, and (A) sec5IR, (C) sec15IR, (E) sec3IR, (G) sec8IR, (I) exo84IR specifically in GFP-marked clone cells (yw, hsflp/w; pmCherry-Atg8a/+; act< FRT, cd2, FRT> GAL4, UAS-GFP/+) analyzed for mCherry-Atg8a puncta. Scale bars represent 20µm.B, D, F, H, J Quantification of data from (A, C, E, G, I). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "exo84: 43163
GAL4: 855828
sec15: 42499
sec3: 39940
sec5: 33563
sec8: 40712"
  },
  {
    "caption": "A Salivary glands dissected from 14 hours after puparium formation (top left) control (fkh-GAL4/+; pmCherry-Atg8a/+), and those with salivary gland-specific knockdown of (middle left) sec5 (fkh-GAL4/w; pmCherry-Atg8a/+; UAS-sec5IR/+), (bottom left) sec15 (fkh-GAL4/w; pmCherry-Atg8a/+; UAS-sec15IR/+), (top right) sec3 (fkh-GAL4/w; pmCherry-Atg8a/UAS-sec3IR), (middle right) sec8 (fkh-GAL4/w; pmCherry-Atg8a/UAS-sec8IR), (bottom right) exo84 (fkh-GAL4/w; pmCherry-Atg8a/UAS-exo84IR) analyzed for mCherry-Atg8a puncta. Scale bars represent 20µm.B Quantification of data from (A). Data are represented as means ± SEM; n≥ 10. Statistical significance was determined using a Student's t test (** p< 0.001, *** p< 0.0001).",
    "ncbi_link": "exo84: 43163
fkh: 43383
GAL4: 855828
sec15: 42499
sec3: 39940
sec5: 33563
sec8: 40712"
  },
  {
    "caption": "A Control animals (+/w; UAS-sec5IR/+), n= 19, and those with salivary gland-specific knockdown of sec5 (fkh-GAL4/w; UAS-sec5IR/+), n=20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.B Quantification of data from (A). Data are represented as means. Statistical significance was determined using a Chi-square test.C Control animals (+/w; UAS-sec15IR/+), n= 20, and those with salivary gland-specific expression sec15 (fkh-GAL4/w; UAS-sec15IR/+), n= 20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.D Quantification of data from (C). Data are represented as means. Statistical significance was determined using a Chi-square test.E Control animals (+/w; UAS-sec3IR/+), n= 20, and those with salivary gland-specific expression sec3 (fkh-GAL4/w; UAS-sec3IR/+), n= 20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.F Quantification of data from (E). Data are represented as means. Statistical significance was determined using a Chi-square test.G Control animals (+/w; UAS-sec8IR/+), n= 20, and those with salivary gland-specific knockdown of sec8 (fkh-GAL4/w; UAS-sec8IR/+), n=19, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.H Quantification of data from (G). Data are represented as means. Statistical significance was determined using a Chi-square test.I Control animals (+/w; UAS-exo84IR/+), n= 19, and those with salivary gland-specific knockdown of exo84 (fkh-GAL4/w; UAS-exo84IR/+), n=20, were analyzed by histology for the presence of salivary gland material (red dotted circle) 24 hours after puparium formation.J Quantification of data from (I). Data are represented as means. Statistical significance was determined using a Chi-square test.",
    "ncbi_link": "exo84: 43163
fkh: 43383
GAL4: 855828
sec15: 42499
sec3: 39940
sec5: 33563
sec8: 40712"
  },
  {
    "caption": "A Salivary glands dissected from late 3rd instar larvae (Gbe Su(H)-lac-Z/w-;+;Fkh-GAL4/+) show less notch activity (left) compared to glands from 14 hours after puparium formation (APF) animals (middle). Down-regulation of ral in salivary glands from 14 hours APF animals (Gbe Su(H)-lac-Z/w-;UAS-ralIR/+;Fkh-GAL4/+) reduces the levels of notch activity (right). Scale bar represents 20µm.B Quantification of data from (A). Data are represented as means ± SEM; n≥ 4. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "Su(H): 43161
Fkh: 43383
GAL4: 855828
Gbe: 37038
ral: 31332"
  },
  {
    "caption": "C Salivary glands dissected from 14 hours after puparium formation animals expressing mCherry-Atg8a in all cells, and notchIR specifically in GFP-marked clone cells (yw, hsflp/w,UAS-notchIR; pmCherry-Atg8a/+; act< FRT, cd2, FRT> GAL4, UAS-GFP/+) analyzed for mCherry-Atg8a puncta. Scale bar represents 20µm.D Quantification of data from (C). Data are represented as means ± SEM; n> 10. Statistical significance was determined using a Student's t test.",
    "ncbi_link": "GAL4: 855828
notch: 31293"
  },
  {
    "caption": "A. U6A cells expressing wild-type or T387A STAT2 were treated with IFN-β (100 IU/ml). Cells were harvested after 4 h and total RNAs were analyzed by real-time PCR. Values are the means ± SD from three independent experiments.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "B. U6A cells expressing wild-type, T387A, or T387D STAT2 were treated with IFN-β (100 IU/ml). Cells were harvested after 4 h and total RNAs were analyzed by real-time PCR. Values are the means ± SD from three independent experiments.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "C, D. U6A cells expressing wild-type or T387A STAT2 were treated with IFN-β for 0, 4, 8, or 24 h. Total RNAs were analyzed by using an Illumina HumanHT-12 v4 Expression BeadChip array. The average signal for each probe was used to determine expression levels. Genes with average signals below 25 and detection P values greater than 0.01 in the untreated or treated cells were excluded from the analysis. Inductions of less than 2-fold were not scored. The Venn diagram shows the numbers of genes induced by 1.2 fold or more in U6A cells expressing T387A STAT2, relative to untreated control cells. The numbers in the table are fold changes calculated from the ratios T387A STAT2 treated / untreated and wild-type STAT2 treated / untreated.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "A. HME cells expressing wild-type, T387A, or T387D STAT2 were seeded in 96-well plates at 8000 cells/well. The cells were exposed to vesicular stomatitis virus (VSV) for 2 h, with or without pre-treatment with IFN-β (100 IU/ml). After 20 h, the amounts of the VSV-M and STAT2 proteins were analyzed by the Western method.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "B, C. HME cells expressing wild-type, T387A, or T387D STAT2 were seeded in 96-well plates at 8000 cells/well. On the second day, the cells were treated with IFN-β (10 IU/ml) for 2 h. The cells were then exposed to different multiplicities of infection of VSV for 2 h, followed by fresh media containing 10 IU/ml of IFN-β. The cells were analyzed by staining with crystal violet (B) after 48 h.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "B, C. HME cells expressing wild-type, T387A, or T387D STAT2 were seeded in 96-well plates at 8000 cells/well. On the second day, the cells were treated with IFN-β (10 IU/ml) for 2 h. The cells were then exposed to different multiplicities of infection of VSV for 2 h, followed by fresh media containing 10 IU/ml of IFN-β. The cells were analyzed by the MTT assay (C) after 48 h.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "D. U6A cells expressing wild-type, T387A, or T387D STAT2 were placed into 96 well plates (2000 cells/well) and the cells were treated with IFN-β (1000 IU/ml) for 96 h. Cell survival was analyzed by the MTT assay. Each experiment was carried out two independent times, with results similar to the representative examples that are shown.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "A. U6A cells expressing wild-type or T387A STAT2 were treated with IFN-β (100 IU/ml) for 30 min or were untreated. The cells were washed with PBS and the media was replaced with fresh media containing staurosporine (500 nM). Whole-cell lysates were harvested and analyzed by the Western method;",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "B. U6A cells expressing wild-type or T387A STAT2 were treated with IFN-β (100 IU/ml) for 4 h or were untreated. Whole-cell lysates were used for immunoprecipitations of IRF9 and Flag-STAT2.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "C. U2A cells expressing wild-type or T387A STAT2 were treated with IFN-β (100 IU/ml) for 4 h or were untreated. Whole-cell lysates were used for immunoprecipitation of Flag-STAT2.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "D. U3A cells expressing wild-type or T387A STAT2 were treated with IFN-β (100 IU/ml) for 4 h or were untreated. Whole-cell lysates were used for immunoprecipitation of Flag-tagged STAT2.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "E. EMSAs using an ISRE probe. Extracts from U6A cells expressing wild-type or T387A STAT2 treated with IFN-β for 1 h were analyzed. The position of ISGF3 is labeled.",
    "ncbi_link": "STAT2: 6773"
  },
  {
    "caption": "(C) Relative expression of the stemness factors SOX2 and OCT4 and the EMT markers SNAIL, Vimentin and TWIST in MCF-7/CD44+ cells. The fold change was calculated using GAPDH as an internal control using the 2-ΔΔCT method comparing stem or non-stem cells versus the total cell line. The box and whiskers graph shows the range, median and quartile interval values from 3 independent experiments.",
    "ncbi_link": "GAPDH: 
OCT4: 5460
SNAIL: 6615
SOX2: 6657
TWIST: 7291
Vimentin: 7431"
  },
  {
    "caption": "(D) miR-10b overexpression affecting stemness and EMT factors. Relative quantification of miR-10b (relative to RNU6B), HOXD10 and RHOC (relative to GAPDH) was performed in MCF-7/CD44+ fractions compared to non-enriched cells. Box plots show the range, median and quartile interval values from 3 independent experiments. A two-tailed Student's t test was used to compare the two groups (p < 0.05). SEM, standard error of the mean; TLDA, TaqMan Low Density Arrays; and EMT, epithelial-mesenchymal transition.",
    "ncbi_link": "GAPDH: 
RNU6B: 
HOXD10: 3236
miR-10b: 406903
RHOC: 389"
  },
  {
    "caption": "(E) Relative expression of stemness factors SOX2 and OCT4 and EMT markers SNAIL and Vimentin in MDA-MB-231/EpCAM+ cells. The fold change was calculated using GAPDH as an internal control using the 2-ΔΔCT method comparing stem or non-stem cells versus the total cells. The box and whiskers graph shows the range, median and quartile interval values from 3 independent experiments.",
    "ncbi_link": "GAPDH: 
OCT4: 5460
SNAIL: 6615
SOX2: 6657
Vimentin: 7431"
  },
  {
    "caption": "(A) Upper panel, left: MCF-7/CD44+ cells were transfected with anti-miR-10b or a scrambled control, and qRT-PCR was performed. Upper panel, right: An aliquot of these cells was subjected to mammosphere-forming assays. The graph shows the mean ± SEM of the number of formed mammospheres per 4000 seeded cells in 3 independent experiments. Lower panel, left: Expression of miR-10b relative to RNU6B in MCF-7 cells stably transfected with a plasmid containing the miR-10b gene versus an empty vector. Results are the mean ± SEM values from 3 independent experiments. Lower panel, right: miR-10b-overexpressing MCF-7 cells analyzed by serial mammosphere assays. The mean ± SEM of the number of formed mammospheres per 4000 seeded cells in 3 independent experiments was plotted on each bar.",
    "ncbi_link": "RNU6B: 
miR-10b: 406903"
  },
  {
    "caption": "(B) Upper panel: Mammosphere formation was performed by seeding 20,000 MDA-MB-231/EpCAM+ cells, and after 3 weeks, the cells were disaggregated, counted, and reseeded. Stable miR-10b-overexpressing cells from 3 independent clones were tested in 3 passages, and cell number was plotted as the mean ± SEM.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "(C) In vivo limiting dilution assays. miR-10-OE or control cells were subcutaneously injected in the backs of mice at 3 doses (1,000, 10,000 and 50,000 cells for MCF-7 and 5000, 10 000 and 20 000 for SKBR-3). Mice were sacrificed after eight weeks, and tumor burden was analyzed using the ELDA software. Plots are depicted in Fig EV2. The tables show the number of mice with tumors versus the total number of mice injected. Below the tables, the estimated frequency (freq) of stem cells for each group and p is shown. Stem cell frequency for MCF-7 cells was 1 in 34252 (range 94888-12364) in miR-10b-OE cells versus 1 in 238965 (Range 1817801-31414) in miR-scr cells. Stem cell frequency for SKBR3 cells was 1 in 5013 (Range 11135-2257) in miR-10b-OE cells versus 1 in 18778 (Range 45397-7767) in miR-scr cells.",
    "ncbi_link": "miR-10: 406902///406903
miR-10b: 406903"
  },
  {
    "caption": "(D) Stemness and EMT marker mRNA levels following miR-10b modulation. miR-10b, OCT4/3, SNAIL and Vimentin expression was quantified in breast cancer cell lines using transient transfection of miR-10b versus a miR-Scr vector (left) or anti-miR-10b versus anti-miR-ctl (right). Log-scale plots show the mean and SEM for the relative expression of each gene from triplicate independent transient transfections, each performed three times. A Mann-Whitney U test was used to compare expression between groups. SOX2, OCT4 and Vimentin were significantly modulated by up- or down-regulation of miR-10b (p=0.0043, p=0.0054 and p=0.000908, respectively). SEM, standard error of the mean.",
    "ncbi_link": "miR-10b: 406903
OCT4: 5460
OCT4/3: 5460
SNAIL: 6615
SOX2: 6657
Vimentin: 7431"
  },
  {
    "caption": "(B) MCF-7, SKBR-3 and T47-D breast cancer cells were transfected with gain- or loss-of-function constructs/shRNAs and their respective controls (a miR-10b-OE plasmid or anti-miR-10b). MREs of the validated target HOXD10 and of the putative targets PTEN and PIK3CA were cloned into pMIR-Report, and dual luciferase reporter assays were performed. A mutated control miR-10b (MRE MUT PTEN) was also included. Bars show the mean ± SEM from 6 independent transfections.",
    "ncbi_link": "HOXD10: 3236
miR-10b: 406903
PIK3CA: 5290
PTEN: 5728"
  },
  {
    "caption": "(C) PTEN and PIK3CA expression after miR-10b modulation. Left panel shows miR-10b, PTEN and PIK3CA expression by qRT-PCR in MCF-7 cells with ectopic miR-10b expression. Right panel shows miR-10b, PTEN and PIK3CA expression by qRT-PCR in MDA-MB-231 cells after antagomiR-10b transfection. Data are from three independent transient transfections performed by triplicate.",
    "ncbi_link": "miR-10b: 406903
PIK3CA: 5290
PTEN: 5728"
  },
  {
    "caption": "(D) To further confirm PTEN targeting, we performed gain- or loss-of-function experiments in breast cancer cell lines (MCF-7, MCF-7/CD44+, SKBR-3 and T47D) by overexpressing miR-10b or inhibiting it with a miR-10b-OE plasmid or anti-miR-10b shRNAs. PTEN and miR-10b levels were measured by qRT-PCR. The log2-fold change of PTEN (left panel) and PIK3CA (right panel) mRNA levels obtained through the 2-ΔΔCT method were plotted against their respective miR-10b expression levels. Correlation analysis was performed [PTEN (r=-0.80), PI3KCA (r=0.43)]. A two-tailed Student's t test was used to compare the two groups (*p < 0.05). SEM, standard error of the mean.",
    "ncbi_link": "miR-10b: 406903
PIK3CA: 5290
PTEN: 5728"
  },
  {
    "caption": "(E) PTEN protein modulation by miR-10b. Upper panel: PTEN protein levels in SKBR-3, and MCF-7 cells were analyzed by Western blot. GAPDH was used as a loading control with cells cultured as in (B). Lower panel: Densitometric analysis of Western blot assays performed with three biological replicates.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "(F) PTEN immunohistochemistry analysis of MCF-7-miR-10b-OE or control MCF-7-miR-Scr-OE tumorxenografts.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "(G) miR-10b overexpression does not increase mammosphere formation in PTEN-depleted cells. MCF-7-miR-Scr-OE cells (left panels) and MCF-7-miR-10b-OE (right panels) were transfected with a Dicer-substrate RNA directed toward PTEN, and after 24 h, quantitative RT-PCR assays for PTEN, SOX2, OCT4, SNAIL and Vimentin were performed. Additionally, the same cells were analyzed for mammosphere formation. The graph shows the mean and standard error of the relative increase of each marker or number of mammospheres in PTEN-depleted cells (black bars) and in cells transfected with a scrambled control (white bars) in three independent biological experiments performed by triplicate.",
    "ncbi_link": "Dicer: 23405
miR-10b: 406903
OCT4: 5460
PTEN: 5728
SNAIL: 6615
SOX2: 6657
Vimentin: 7431"
  },
  {
    "caption": "(H) T47-D cells were transfected with antagomiR-10b, a dsi-RNA for PTEN or both and mammospheres produced as described in material and methods. Bars show mean and SEM from three independent experiments. * p=0.003 by Student´s T test, after ANOVA showing statistical differences in groups.",
    "ncbi_link": "dsi: 23405
miR-10b: 406903
PTEN: 5728"
  },
  {
    "caption": "(I) PTEN overexpression compensates for miR-10b overexpression. Left panel: MDA-468 cells were transfected with a plasmid overexpressing wild-type PTEN or a version containing a mutated MRE in its 3'-UTR, with or without a plasmid containing miR10b and PTEN mRNA expression was measured by end-point RT-PCR. Middle panel: Relative expression of stemness factor SNAIL. The plots show the relative expression from biological triplicate analyses (mean and SE shown). Right panel: Relative expression of stemness factor SOX2. The plots show the relative expression from biological triplicate analyses (mean and SE shown).",
    "ncbi_link": "miR-10b: 406903
miR10b: 406903
PTEN: 5728
SNAIL: 6615
SOX2: 6657"
  },
  {
    "caption": "(B) Upper panel. Cultures were serum-starved for 18 h and then stimulated with insulin or exposed to the PI3K pathway inhibitors Wortmannin or LY294002. PTEN, PI3KCA, GSK3 and phospho-AKT Ser-473 protein levels were analyzed by Western blot. GAPDH was used as a loading control. AKT kinase activity was analyzed in these cells by immunoprecipitating phosphorylated AKT proteins with a p-AKT-Ser-473 antibody and using chimeric GSK-3 as a substrate. A two-tailed Student's t test was used to compare the two groups (p<0.05). SEM, standard error of the mean. Lower panel. SKBR3 cells were transiently transfected with a plasmid containing an open reading frame of PTEN, miR-10b or both and phospho-AKT, AKT or tubulin levels analyzed by Western Blot assays. Control is empty vector-transfected cells.",
    "ncbi_link": "miR-10b: 406903
PTEN: 5728"
  },
  {
    "caption": "(C) Clonogenic ability of miR-10b-depleted CD44+ MCF-7 cells after PI3K pathway inhibition. Cultures were serum-starved for 18 h and then stimulated with insulin or exposed to the PI3K pathway inhibitors wortmannin or LY294002. Cells transfected with anti-miR-10b or a scrambled control (anti-miR-ctl) were seeded in soft agar at clonal density and exposed to insulin or PIK3CA inhibitors. After 3 weeks, colonies were quantified. Bars show the mean ± SEM for 3 independent experiments.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "(D) miR-10b overexpression does not induce additional changes in cell colony numbers in response to insulin or PI3K inactivation. MCF-7 stable miR-Scr-OE or miR-10b-OE cells were seeded in soft agar at clonal density and exposed to insulin or PIK3CA inhibitors. After 3 weeks, colonies were quantified. Bars show the mean ± SEM for 3 independent experiments.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "HIF-1α ChIP-seq signal in the HIF-2α KO cells was plotted against that in the wild-type cells for all canonical HIF-1 binding sites in either cell type",
    "ncbi_link": "HIF-2α: 2034"
  },
  {
    "caption": "HIF-2α ChIP-seq signal in the HIF-1α KO cells was plotted against that in the wild-type cells for all canonical HIF-2 binding sites in either cell type. No significant increase (Wilcoxon rank sum test) in binding of either isoform was observed following deletion of the other",
    "ncbi_link": "HIF-1α: 3091"
  },
  {
    "caption": "Box-and-whisker plots showing: (D) The effect of HIF-2α inactivation on HIF-1α ChIP-seq signal at sites that specifically bound HIF-2α, but not HIF-1α in wild-type cells showing a slight, but significant (p = 4 x 10-5, Wilcoxon signed rank test) decrease rather than increase (compare red boxes) consistent with the reduction in HIF-1α protein observed in panel A",
    "ncbi_link": "HIF-2α: 2034"
  },
  {
    "caption": "The effect of HIF-1α inactivation on HIF-2α ChIP-seq signal (compare blue boxes) at sites that specifically bound HIF-1α, but not HIF-2α in wild-type cells showing no significant effect (p = 0.5, Wilcoxon signed rank test)",
    "ncbi_link": "HIF-1α: 3091"
  },
  {
    "caption": "The effect, at sites that bind both isoforms in wild-type cells, of (F) HIF-2α inactivation on HIF-1α binding intensity showing a similar small but significant reduction rather than increase (p = 2 x 10-16, Wilcoxon Signed rank test) as abov",
    "ncbi_link": "HIF-2α: 2034"
  },
  {
    "caption": "The effect, at sites that bind both isoforms in wild-type cells, o HIF-1α inactivation on HIF-2α binding intensity showing no significant effect (p = 0.4, Wilcoxon signed rank test)",
    "ncbi_link": "HIF-1α: 3091"
  },
  {
    "caption": "Parental and TGF-β isogenic cell lines were treated with 50nM volasertib for 72 hours. Cells were then harvested, and lysates were immunoblotted for cleaved PARP and γH2AX proteins were subsequently quantitated and normalized with β-actin (B).",
    "ncbi_link": "TGF-β: 7040"
  },
  {
    "caption": "Calu6, H157, and H1355 TPR-Met-expressing or vector control (pBABE)-expressing cells were treated as indicated for 24 hours and apoptosis was measured using the Apo-BrdU assay.",
    "ncbi_link": "Met: 4233
TPR: 7175"
  },
  {
    "caption": "Parental and TPR-Met-expressing cell lines were treated with the indicated drugs for 24 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins. β-actin was used as a loading control.",
    "ncbi_link": "Met: 4233
TPR: 7175"
  },
  {
    "caption": "Parental and TPR-Met-expressing cell lines were treated as indicated for 24 hours and allowed to grow in drug-free medium for 15-20 days to form colonies, which were counted using ImageJ. Data are means ± standard error of the mean from three independent experiments. Significant differences using two-way analysis of variance with Bonferroni or Benjamini-Hochberg correction for multiple comparisons are indicated.",
    "ncbi_link": "Met: 4233
TPR: 7175"
  },
  {
    "caption": "Mesenchymal NSCLC cell lines with the noted MET alterations were incubated with 50nM volasertib for four hours and subjected to immunoblotting with the indicated antibodies. *p < 0.05. **p < 0.01.",
    "ncbi_link": "MET: 4233"
  },
  {
    "caption": "Basal protein and mRNA expression in parental and VAR cells for the indicated proteins was measured using immunoblotting (upper) and reverse-transcriptase PCR (lower), with GAPDH expression used for normalization.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Epithelial and mesenchymal NSCLC cell lines after Plk1 silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "ncbi_link": "Plk1: 5347"
  },
  {
    "caption": "Calu6 and H1792 mesenchymal NSCLC cell lines after VIM silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "ncbi_link": "VIM: 7431"
  },
  {
    "caption": "Calu6 (mesenchymal) and H1975 (epithelial) NSCLC cell lines after Plk1 and INTB1 silencing with siRNA for 48 hours. Cells were then harvested, and lysates were immunoblotted for the indicated proteins.",
    "ncbi_link": "INTB1: 3688
Plk1: 5347"
  },
  {
    "caption": "A, B, and C. Immunostaining of Tom20 (mitochondria) in cells positive for β3-tubulin in DIV6 Ifnb+/+ and Ifnb-/- CNs with or without rIFN-β for 24 h. A. Projection of 3D image of Tom20. Scale bars equal 20 microns. B. Quantification of total mitochondrial mass per neuron. C. Mean individual mitochondria volume in Ifnb+/+ and Ifnb-/- CNs. ",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "D, E, F, and G. 3D electron microscopy of thalamus in 12-month-old Ifnb+/+ and Ifnb-/- mice. D. Volume rendering of mitochondria (left panel) and corresponding mitochondria in 2D electron microscopy image (right panel) in cell bodies. Each individual mitochondrion is colored differently. Scale bars equal 2 microns. Voxel size equals 0.00878908x0.00878908x0.03 microns for the Ifnb+/+ neuron and 0.00439453x0.00438453x0.04 microns for Ifnb-/-. Nuclei are in grey and marked with 'N.' E. Reconstituted axonal mitochondria. Images extracted from Movies EV1 and 2. F. Size of individual mitochondria in cell bodies and non-myelinated and myelinated axons. N>30; error bars are SD. G. Number of branches per mitochondrion. N>30; error bars are SD. ",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "D-E. Respiration of isolated mitochondria from Ifnb+/+ and Ifnb-/- whole brains. OCR measurements under Complex 1 substrates (pyruvate/malate) were obtained at baseline (B) and on addition of ADP, oligomycin, FCCP and rotenone/antimycin A to capture S3, S4o, S3u, and nonmitochondrial respiration. N=3-4 mice per group; bar graphs show mean + SE.",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "K. Immunofluorescence of 8OHdG in CN cultures. Neurons were labeled with Nissl. Scale bars equal 50 microns. L. Quantification of 8OHdG by ELISA in brain tissues in young (aged 1.5-3 months) and old (aged 6-12 months) Ifnb+/+ and Ifnb-/- mice. ",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "M. Immunoblot for optineurin in 6-week-old midbrains of Ifnb+/+ and Ifnb-/- mice. N. Immunoblot for optineurin in DIV6 Ifnb+/+ and Ifnb-/- CNs with or without 30 U/mL rIFN-β.",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "I. MFN2 and OPA1 immunoblots and quantification in Ifnb+/+ and Ifnb-/- CN cultures and quantification. Vinculin was used as a loading control. Error bars are SEM from 3 independent experiments.",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "J. Optineurin and Tom20 immunofluorescence in Ifnb+/+ and Ifnb-/- MEFs transfected with Drp1 or phosphomimetic Drp1.",
    "ncbi_link": "Drp1: 74006
Ifnb: 15977"
  },
  {
    "caption": "E. Volume rendering from 3D TEM images of Ifnb+/+ and Ifnb-/- thalami. Mitochondria are blue, the ER is yellow, and nuclei are grey. Mitochondria undergoing fission are cyan and indicated with a white arrow. 2D pictures are shown in Fig 2.",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "H. Projections of 3D images from immunostaining of Drp1 (blue), Hsp60 (mitochondria, green), INF2 (yellow), and calnexin (ER, magenta) in Ifnb-/- MEFs with or without rIFN-β treatment for 6 h. Scale bar equal 2 microns. Arrows indicate fission foci. I. Quantifications of triple-positive MT-DR+Drp1+Cnx+ in MEFs. Images are shown in Fig EV3. ",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "D. Projections of 3D images from immunostaining for phospho-S622 Drp1 (yellow), Hsp60 (mitochondria, green), and calnexin (ER, magenta) in N2A cells depleted of STAT5 A and B (δStat5) or IFN-β (δIfnb) or with nontargeting control (NTC). Cells with or without rIFN-β treatment for 6 h. Scale bar equals 5 microns. Arrows indicate triple-positive foci. E. Quantification of D. ",
    "ncbi_link": "δIfnb: 15977
STAT5 A: 20850"
  },
  {
    "caption": "M. Optineurin immunostaining in Ifnb+/+ and Ifnb-/- MEFs overexpressing PGAM5 and quantification. Empty vector was used as control. Additional controls are shown in Fig EV5L. Error bars are SD from N=30 cells.",
    "ncbi_link": "Ifnb: 15977
PGAM5: 72542"
  },
  {
    "caption": "B) Immunoblot of NDC80 levels following depletion of the Ndc80 complex by RNAi.",
    "ncbi_link": "Ndc80: 10403"
  },
  {
    "caption": "B. Representative immunoblot of transfected missense ROS1 TKD mutations in transfected HEK-293A lysates.",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "C. Densitometry analysis of immunoblots (N = 3, biological replicates) as represented in (B). Fold-change in relative ROS1 phosphorylation is calculated by first calculating the ratio of phospho-ROS1 to total ROS1 protein for each variant and then normalizing to ROS1WT. One-way ANOVA and Sidak's test were used to control for multiple comparisons in C Error bars in figure represent mean ± SEM.",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "D. Representative immunoblot of ROS1 D2113 position substitutions (E, G, Y, and Q as indicated) in HEK-293A cells. E. Densitometry of immunoblots (N = 3, biological replicates) as represented in (D). pROS1- phospho-ROS1, tROS1- total-ROS1. One-way ANOVA and Sidak's test were used to control for multiple comparisons in E. Error bars in figure represent mean ± SEM.",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "A. Immunoblot analysis of phospho-ROS1 and total ROS1 protein expression of NIH-3T3 cells stably transduced with empty vector (EV) or indicated ROS1 TKD mutants",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "C. Soft-agar assay of NIH-3T3 ROS1D2113N compared with NIH-3T3 SLC-ROS1 fusion cells (positive control) or ROS1K1980E (kinase-dead, negative control). +/- lorlatinib treated samples were compared for significance using two-way RM ANOVA (matching across rows, N = 3, biological replicates) with Šídák's multiple comparisons test (P values are indicated in figure)",
    "ncbi_link": "SLC: 
ROS1: 6098"
  },
  {
    "caption": "D. Immunoblot analysis of phospho-ROS1 and total ROS1 protein expression in MCF10A cells stably transduced with indicated ROS1 variants",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "Cell proliferation data showing effects of treatment with DMSO (Vehicle), crizotinib (250nM), lorlatinib (250 nM), and NVL-520 (250 nM) in MCF10A ROS1 wildtype (WT) (G), D2113N (H), D2113G (I) and SLC34A2-ROS1 (SLC-ROS1) (J) as indicated. Ordinary One-way ANOVA with Dunnett's multiple comparisons test was used to determine significant differences. N = 6 wells, biological replicates (H-I). Error bars in figure represent mean ± SEM.",
    "ncbi_link": "SLC: 
SLC34A2: 
ROS1: 6098"
  },
  {
    "caption": "A-B. Volcano plots of statistical discoveries from IMAC-enriched (A) and phospho-tyrosine-enriched (B) phosphoproteomic spectral counts comparing ROS1D2113N data to ROS1WT. Select phosphosites linked to indicated cellular functions are annotated within the graph. Unpaired t tests of log2 transformed counts from ROS1WT and ROS1D2113N cells were conducted using Graphpad Prism with variance assumption of individual variance for each role (N=3, biological replicates). Multiple Comparison tests used False Discovery Rate (FDR) with two-stage step-up (Benjamini, Krieger, and Yekutieli) with desired FDR of 5%. X axis features log2-transformed ratio of normalized intensities of ROS1D2113N relative to ROS1WT while y axis features corresponding log10(q) values.",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "A. Immunoblotting was performed on cell lysates generated via transient transfection of the following plasmids: pCX4 ROS1 wildtype (WT), ROS1D2113G (D2113G), ROS1D2113N (D2113N) and the ROS1 fusions, CD74-ROS1, EZR-ROS1 and SLC34A2-ROS1 (SLC-ROS1). The targets interrogated are indicated in the labels on the left side of the image panels and the catalog numbers as well as dilution for antibodies are reported in Methods. B. Immunoblot densitometry graphs to quantitatively compare activation of ROS1, SHP2, ERK1/2 and STAT3 (N = 2, biological replicates). Fusions are listed only by fusion partner: CD74-ROS1 (CD74), EZR-ROS1 (EZR), SLC34A2-ROS1 (SLC).",
    "ncbi_link": "EZR: 
SLC: 
SLC34A2: 
CD74: 972
ROS1: 6098"
  },
  {
    "caption": "C. Immunoblotting was performed on cell lysates generated from stable HEK293A ROS1D2113N, HEK293A CD74-ROS1 and NIH ROS1D2113N and NIH3T3 CD74-ROS1 after treatment with ROS1 TKI. HEK293A stable cell lines were treated with DMSO, 100 nM entrectinib and 100 nM lorlatinib, and NIH3T3 stable cell lines were treated with 25 nM and 100 nM lorlatinib. The targets interrogated are indicated in the labels on the left side of the image panels in HEK293 images and on the right side of image panels in NIH3T3 images. D. Immunoblot densitometry graphs to quantitatively compare extent of inhibition ROS1, SHP2, ERK1/2 and STAT3 and AKT1 phosphorylation from two independent replicate experiments. Pixel density of phosphorylated protein signal was divded by total protein signal, and this ratio was internally normalized to DMSO (Vehicle) treated cell ratio. Note that only the 100 nM lorlatinib condition that was common to the HEK293A and NIH3T3 experiments is depicted in graphs.",
    "ncbi_link": "CD74: 972
ROS1: 6098"
  },
  {
    "caption": "B. Kaplan-Meier survival curve of mice described in (A). Comparison of survival curves using Log-rank (Mantel-Cox) test was used to compare difference between EV (N = 5) and D2113N (N = 5), and EV and SLC34A2-ROS1 (N = 4); significance is indicated as P values within graph.",
    "ncbi_link": "SLC34A2: 
ROS1: 6098"
  },
  {
    "caption": "G. Immunoblot analysis of the phosphorylated (p) and total (t) proteins from NIH-3T3 ROS1D2113N P1 cell lysates prepared from cells treated with vehicle (DMSO) or 10, 100, or 500 nM of crizotinib, entrectinib, or lorlatinib for 4 hours.",
    "ncbi_link": "ROS1: 6098"
  },
  {
    "caption": "LMS (red) and HMS (black) gene expression quantification in Epi cells by random-primed RT-qPCR relative to RPL11 and represented as log2 fold change to CTR. Each dot corresponds to an independent replicate, bars represent Mean ± Standard Deviation values.",
    "ncbi_link": "RPL11: 6135"
  },
  {
    "caption": "Metagene profiling within the 10 kb window around TSS of H3K27ac, LSD1 and H3K4me2 over IgG in Epi cells expressing none (CTR) or different HOTAIR variants (HOT, HOTΔP and HOTΔL). bp stands for base pairs.",
    "ncbi_link": "HOT: 100124700
HOTAIR: 100124700"
  },
  {
    "caption": "Metagene profiling of H3K27ac, LSD1 and H3K4me2 over IgG within the 5 kb window of enhancers in Epi cells expressing none (CTR) or different HOTAIR variants (HOT, HOTΔP and HOTΔL). bp stands for base pairs.",
    "ncbi_link": "HOT: 100124700
HOTAIR: 100124700"
  },
  {
    "caption": "B) Western blot detection of DOT1L  and TUBULIN  (TUB) in whole testicular  protein extracts from CTL and Dot1l-KO (KO) adult mice.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "D) Western blot  detection of DOT1L  and H3K79me2 in Dot1l-KO (KO) and CTL germ cells. Normalization was performed by detecting the membrane with anti-TUBULIN  (TUB). SC  = primary spermatocytes, RS = round spermatids.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "B) Histology  of Dot1l-KO and CTL testes  (periodic acid-Schiff staining). Scale bars indicate 200µm.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "D) Results from the  tests  of fertility (natural mating) of Dot1l-KO and CTL males  (7 males  in each group mated for ~3 months with wild-type females). Schematic diagrams representing the number of litters  and the litter  size from progeny of Dot1l-KO or CTL males  (mean ± SEM).The p-value obtained with a Student t-test is indicated on each graph.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "C) Scatter plots (mean values following angular transformation ± SEM) of the percentage of motile and progressively motile spermatozoa  in Dot1l-KO and CTL adult mice  (N= 12 biological replicates for CTL and 10 biological replicates for Dot1l-KO) obtained following CASA  (computer-assisted sperm analysis). ***p-value <0.0005 (Mann Whitney test performed after angular transformation of the percentages).",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "F) Western blot  detection of  transition protein 2  (TNP2) in spermatozoa  from Dot1l-KO and CTL males. The same quantity of material was loaded in each well (i.e. extracts from 2 million spermatozoa).",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "G) Coomassie-stained  protamine extracts from CTL and Dot1l-KO spermatozoa  following acid urea gel electrophoresis  (same gel, two different intensities). The same quantity of material has been loaded in each well (i.e. extracts from 1.4 million spermatozoa). Protamine 1  and 2 bands (PRM1  and PRM2, respectively) are detected at the bottom of the gel. The rectangle highlights the bands that are likely immature forms of Protamine 2 (i.e. non-cleaved precursor forms). The right panel shows a western blot detection using anti-PRM2  antibody which confirms that one of the high molecular weight band only observed in Dot1l-KO spermatozoa  is an immature form of  Protamine 2 (Pre-PRM2). The corresponding Coomassie-stained gel is also shown.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "H) Quantification of histones TH2B  and H3  (N= 11 and 10 biological replicates for CTL and KO, respectively), of TNP2  (N= 8 biological replicates for CTL and for KO) and of PRM1/PRM2  ratio (N= 3 biological replicates for CTL and for KO) in Dot1l-KO and CTL spermatozoa, related to Fig 3E-G. The data shown are normalized to control mean values (± SEM). *p-value <0.05, ***p-value <0.0005 (unpaired t-tests). A.U. = arbitrary units.",
    "ncbi_link": "Dot1l: 208266"
  },
  {
    "caption": "C Representative renal H&E images (left) with quantitative pathological scores (right) of WT (n = 8) and Ehmt2Ksp mice (n = 7) at day three after renal I/R injury (I/R 3D).",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "G, H Representative immunoblots (G) and quantitative results (H) of p-Rip3 and p-Mlkl of WT (n = 3) and Ehmt2Ksp mice (n = 3) under I/R 3D injury.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "I Representative Sirius Red staining (left) with quantitative results (right) on the kidney sections of WT (n = 7) and Ehmt2Ksp (n = 4) mice at day seven after renal I/R injury (I/R 7D).",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "K Representative TUNEL staining (left) with quantitative results (right) of WT (n = 8) and Ehmt2Ksp mice (n = 4) under I/R 7D injury.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "qPCR validation (C) of indicated genes related to fatty acid metabolism of WT+NI (n = 6), Ehmt2Ksp+NI (n = 6), WT+I/R 3D (n = 6) and Ehmt2Ksp+I/R 3D (n = 6) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "qPCR validation (E) of indicated genes related to fatty acid beta-oxidation of WT+NI (n = 6), Ehmt2Ksp+NI (n = 6), WT+I/R 3D (n = 6) and Ehmt2Ksp+I/R 3D (n = 6) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "H Representative immunoblots (left) with quantitative results (right) of Ces1 level in the kidneys of WT (n = 3) and Ehmt2Ksp (n = 3) mice at I/R 3D.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "C mRNA levels of Kim1 and Ngal of PBS+NI (n = 6), A366+NI (n = 5), PBS+I/R 3D (n = 6) and A366+I/R 3D (n = 5) groups.",
    "ncbi_link": "Kim1: 171283
Ngal: 16819"
  },
  {
    "caption": "Representative images (M) with quantitative results of lipid droplet areas (N) and percentage of different lipid droplet size (O), in labeled-PA treated mPTECs isolated from WT and Ehmt2Ksp mice at one hour after treatment. The results were obtained from three biological replicates; a total of 20 cells were imaged in each group for quantification of lipid droplet area (N, O)",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "Q-S Seahorse studies (Q) with quantitative results of basal (R) and maximal (S) respiration in PA-treated mPTECs isolated from WT and Ehmt2Ksp mice. OCR, oxygen consumption rate; n = 4 cultures.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "E Representative Oil Red O staining with quantification of WT+Veh (n = 5), WT+WWL (n = 4), Ehmt2Ksp+Veh (n = 4) and Ehmt2Ksp+WWL (n = 4) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "F mRNA levels of fatty acid oxidation related genes of WT+Veh (n = 5), WT+WWL (n = 4), Ehmt2Ksp+Veh (n = 4) and Ehmt2Ksp+WWL (n = 4) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "G Representative Cpt1a immunostaining with quantitative analysis in the kidneys of WT+Veh (n = 5), WT+WWL (n = 4), Ehmt2Ksp+Veh (n = 4) and Ehmt2Ksp+WWL (n = 4) groups. Scale bar = 50 μm. IOD, integral optical density.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "Representative immunostaining for CD3 and F4/80 (K) of WT+Veh (n = 5), WT+WWL (n = 4), Ehmt2Ksp+Veh (n = 4) and Ehmt2Ksp+WWL (n = 4) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "Representative CD3 and F4/80 quantitative results (L) of WT+Veh (n = 5), WT+WWL (n = 4), Ehmt2Ksp+Veh (n = 4) and Ehmt2Ksp+WWL (n = 4) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "M Representative immunoblots (left) with quantitative results (right) of p-Mlkl for WT+Veh (n = 3), WT+WWL (n = 3), Ehmt2Ksp+Veh (n = 3) and Ehmt2Ksp+WWL (n = 3) groups.",
    "ncbi_link": "Ehmt2: 110147"
  },
  {
    "caption": "B mRNA levels of Kim1 and Ngal of indicated groups.",
    "ncbi_link": "Kim1: 171283
Ngal: 16819"
  },
  {
    "caption": "D. Validation of selected CRISPR screening hits by targeted gene inactivation. Genes are plotted on the x-axis from lowest FDR value (IFIT1) to highest FDR value (CD163L1) as determined by MAGeCK analysis of the genome-wide screen. All samples were normalized to non-targeting controls ("Non-Targ") for graphing. Graphs represent the mean with error bars representing standard deviation. One-way ANOVA with Dunnett's test comparing each group to the non-targeting control was performed on non-normalized data, n=3 biological replicates.",
    "ncbi_link": "CRISPR: 
CD163L1: 283316
IFIT1: 3434"
  },
  {
    "caption": "D. Heat maps of FPKM (Left) and log2FC (Right) values (from RNA-Seq) of IFN-induced CRISPR screening hits at 6 and 24 h post IFN-treatment. Heatmap intensity represents the mean of 3 independent biological replicates.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "E. Western Blots from lysates of U-2 OS cells treated with IFNβ (20 U/mL) for 6 and 24 h. Antibodies were used to probe for IFN-induced CRISPR screening hits.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "A. Effects of CRISPR-based gene inactivation of IRF9, STAT1, and STAT2 or ZC3HAV1, IFIT3, and IFIT1 on VEEV infection (MOI of 10 for 5 h) in U-2 OS cells with IFNβ pretreatment (20 U/mL for 24 h). B. Effects of CRISPR-based gene inactivation of IRF9, STAT1, and STAT2 or ZC3HAV1, IFIT3, and IFIT1 on VEEV infection (MOI of 10 for 4.5 h) in Huh7.5 cells with (+ symbols) and without (- symbols) IFNβ pretreatment (100 U/mL for 24 h). Data information: data are presented as mean +/- standard deviation. n=3 independent biological replicates, one-way ANOVA with Dunnett's test. ns p > 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.",
    "ncbi_link": "CRISPR: 
IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZC3HAV1: 56829"
  },
  {
    "caption": "D. Dose response curve of IFNβ pretreatment (Left, 2-fold dilutions from 200 U/mL to 1.6 U/mL for 24 h) or IFNλ pretreatment (Right, 2-fold dilutions from 500 ng/mL to 3.9 ng/mL for 24 h) demonstrating inhibition of VEEV infection (MOI of 5 for 5 h) in control (circles), IRF9/STAT1/STAT2-targeted (squares), or ZAP/IFIT3/IFIT1-targeted (triangles) U-2 OS cells. Graphs represent the mean of normalized and transformed (from %Infection to %Inhibition) data for 3 biological replicates with error bars representing standard deviation.",
    "ncbi_link": "IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "A. U-2 OS control, IRF9/STAT1/STAT2-targeted, and ZAP/IFIT3/IFIT1-targeted cells were infected with GFP-expressing ONNV virus (left) or ZIKV (right) after IFNβ pretreatment (20 U/mL). Data information: In data are presented as mean +/- standard deviation. n=3 independent biological replicates, one-way ANOVA with Dunnett's test. ns p > 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.",
    "ncbi_link": "IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "B. Huh7.5 control, IRF9/STAT1/STAT2-targeted, and ZAP/IFIT3/IFIT1-targeted cells were infected with GFP-expressing Sindbis virus (AR86 strain, left) or vesicular stomatitis virus (right) after IFNβ pretreatment (100 U/mL). The percentage of infected (GFP+) cells was quantified by flow cytometry. Data information: In data are presented as mean +/- standard deviation. n=3 independent biological replicates, one-way ANOVA with Dunnett's test. ns p > 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.",
    "ncbi_link": "IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "A. Heatmaps showing the ratio of infected cells at 6, 9, and 12 h of infection with VEEV-GFP. U-2 OS control, IRF9/STAT1/STAT2-targeted, or ZAP/IFIT3/IFIT1-targeted cells were treated with or without IFNβ (20 U/mL for 24 h) and infected with an MOI of 0.5 (left), 1 (middle), or 5 (right) of VEEV-GFP. Infection was quantified by flow cytometry. Heatmap intensity represents the mean of 3 independent biological replicates.",
    "ncbi_link": "IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "B. (Top) Quantification of VEEV production (12 h post-infection, MOI of 2, titered in BHK-21J cells) by plaque assay of control (far left: without IFN-pretreatment), IRF9/STAT1/STAT2-targeted, or ZAP/IFIT3/IFIT1-targeted cells after IFNβ pretreatment (IFNβ 20 U/mL for 24 h). (Bottom) Western blot shows IFN-mediated induction and CRISPR-based targeting of IRF9, STAT1, STAT2, ZAP, IFIT3, and IFIT1. Red asterisks denote long (**) and short (*) isoform of ZAP. Data information: data are presented as mean +/- standard deviation. n=3 independent biological replicates, one-way ANOVA with Dunnett's test on log transformed data. ns p > 0.05, ***p < 0.001, and ****p < 0.0001.",
    "ncbi_link": "CRISPR: 
IFIT1: 3434
IFIT3: 3437
IRF9: 10379
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "C. (Top) Quantification of VEEV production (12 h post-infection, MOI of 2, titered in BHK-21J cells) by plaque assay in control (far left: without IFN-pretreatment), IRF9/STAT1/STAT2-targeted, ZAP/IFIT3/IFIT1-targeted, or ZAP/IFIT3/IFIT1-targeted cells that were subsequently CRISPR targeted with a guide targeting BST2, RSAD2, ISG20, or IFITM3  after IFNβ pretreatment (IFNβ 20 U/mL for 24 h). (Bottom) Western blot shows IFN-mediated induction and CRISPR-based targeting of BST2, RSAD2, ISG20, and IFITM3. Black squares denote non-specific bands. Data information data are presented as mean +/- standard deviation. n=3 independent biological replicates, one-way ANOVA with Dunnett's test on log transformed data. ns p > 0.05, ***p < 0.001, and ****p < 0.0001.",
    "ncbi_link": "CRISPR: 
BST2: 684
IFIT1: 3434
IFIT3: 3437
IFITM3: 66141
IRF9: 10379
ISG20: 3669
RSAD2: 91543
STAT1: 6772
STAT2: 6773
ZAP: 56829"
  },
  {
    "caption": "Growth phenotypes of the wild-type (WT, Col-0), bri1-null mutant, and two independent ubp12i/ubp13 double mutant lines grown on 1/2MS medium supplemented with 10 μM DEX (DEX medium) for 10 days and transferred to DEX medium containing 1 μM BL or mock solution (0.1% [v/v] EtOH) for additionally 8 days. Scale bars: 10 mm.",
    "ncbi_link": "bri1: 830095
ubp12: 830548
ubp13: 820364"
  },
  {
    "caption": "Phenotype of the WT and ubp12i/ubp13 double mutant grown on DEX medium in the presence of increasing concentrations of BL in the light for 6 days. Scale bars: 10 mm.   Hypocotyl length relative to the mock control of seedlings (B). Experiments were done in triplicate (n >15 seedlings for each line).  ",
    "ncbi_link": "ubp12: 830548
ubp13: 820364"
  },
  {
    "caption": "Western blot analysis of BRI1 protein amount in ubp12i/ubp13 plants with the α-BRI1 antibody. Total proteins were isolated from 18-day-old plants grown on 1/2MS medium supplemented with 10 μM DEX (+) or not (-).   Western blot analysis of BRI1 protein level in concanamycin A (ConcA)-treated plants. Eighteen-day-old plants were grown on DEX medium and exposed to 1 μM ConcA for 4 h before total protein isolation.  ",
    "ncbi_link": "ubp12: 830548
ubp13: 820364"
  },
  {
    "caption": "Growth phenotype comparison of BRI1-mCit/bri1/ubp12i/ubp13 and BRI125KR-mCit/bri1/ubp12i/ubp13. The indicated transgenic lines were grown on DEX medium for 18 days. Scale bars: 10 mm.",
    "ncbi_link": "mCit: 
BRI1: 830095
bri1: 830095
ubp12: 830548
ubp13: 820364"
  },
  {
    "caption": "Western blot analysis monitoring the BRI1 protein accumulation in BRI125KR-mCit/bri1/ubp12i/ubp13 plants with the α-BRI1 antibody. Total proteins were isolated from the roots of the lines indicated (A). PEPC was used as a loading control.",
    "ncbi_link": "mCit: 
BRI1: 830095
bri1: 830095
ubp12: 830548
ubp13: 820364"
  },
  {
    "caption": "A-D Analysis of the BRI1 vacuolar targeting on Arabidopsis seedlings expressing BRI1 (A) or BRI125KR (C) tagged with mCitrine (mCit) in either bri1/UBP12/UBP13 or bri1/ubp12i/ubp13 background. Six-day-old seedlings were grown on DEX medium, and kept in the dark for 2 h in the presence of 50 μM CHX before imaging. Confocal images of epidermal cells from root meristem are shown. Scale bars: 10 μm. Measurements of the relative PM/intracellular BRI1-mCit fluorescence intensity. For each line, at least 55 and 25 cells from over 25 and 15 seedlings were measured in (B) and (D), respectively.",
    "ncbi_link": "mCit: 
mCitrine: 
bri1: 830095
UBP12: 830548
ubp12: 830548
UBP13: 820364
ubp13: 820364"
  },
  {
    "caption": "A-C. CHO  cells expressing   PD-L1 alone (A) or co-expressing CD80  (B) or CD86   (C) were stained  with CD80  Ig,  PD-1 Ig, CTLA-4 Ig or anti-PD-L1  Ab clones MIH1, MIH3, 29E.2A3) at 1µg/ml for 30 min at 37°C. Representative FACS  plots show staining  plotted against total PD-L1 mCherry  levels.",
    "ncbi_link": "PD-L1: 919
CD80: 941
CD86: 942"
  },
  {
    "caption": "A. Transendocytosis  assays were carried out overnight using CHO  donor cells (CD80GFP alone or CD80GFP with PD-L1mCherry co-expression) incubated with  CTLA-4 recipient cells at a ratio of 1:1. Recipient cells either lacked CTLA-4 (No CTLA-4) or expressed  CTLA-4. FACS  plots show  CD80GFP ligand loss from donor cells highlighted in blue quadrants in the presence of CTLA-4+ recipients.",
    "ncbi_link": "GFP: 
mCherry: 
PD-L1: 919
CD80: 941
CTLA-4: 1493"
  },
  {
    "caption": "C-F. Transendocytosis  assays were performed at a ratio of 2 donor:1  CTLA-4 recipient for the times  indicated. (C), Representative FACS  plots showing CD80GFP levels and (D) full kinetic  analysis of CD80  or CD86  downregulation on donor cells quantified as a percentage relative to no  CTLA-4  control (mean ± SEM, 3 independent experiments, ns - not significant: two-way ANOVA with Tukey's multiple comparisons test). (E) Representative FACS  plots showing PD-L1mCherry level at time points indicated. (F) Full kinetic  analysis of PD-L1mCherry level on donor cells (mean ± SEM, 3 independent experiments).",
    "ncbi_link": "CTLA-4: 1493"
  },
  {
    "caption": "D. Levels of CD86GFP and PD-L1mCherry remaining on donor cells over a 24h transendocytosis  period with CTLA-4 WT or Del36 plotted relative to no  CTLA-4 control (mean ± SEM, 6 independent experiments). ****P≤0.0001, RM one-way ANOVA.",
    "ncbi_link": "CTLA-4: 1493"
  },
  {
    "caption": "A-B. APC-labelled PD-1 Ig (0.75µg/ml) was used to detect PD-L1 in DG-75 cells co-expressing CD80GFP  (A) or CD86GFP (B). Staining  was carried out following transendocytosis  using Jurkat  cells expressing no CTLA-4, CTLA-4 WT or CTLA-4  Del36 (at a ratio of 1:1) for the indicated durations. (A) shows representative FACS  plots of CD80GFP  vs.  PD-1 Ig at the time points indicated, with full kinetic  data plotted below (mean ± SEM, 3 independent experiments, ***P≤0.001, ****P≤0.0001: two-way ANOVA with Tukey's multiple comparisons test). (B) As for (A) except using CD86-PD-L1  expressing cells.",
    "ncbi_link": "CTLA-4: 1493"
  },
  {
    "caption": "A. Staining  of free PD-L1  with APC-conjugated PD-1 Ig in DG-75 cells expressing only PD-L1mCherry, using cell lines with increasing ratios of CD80GFP:  PD-L1mCherry compared to CD80GFP only. FACS  plots are representative of 4 independent experiments.",
    "ncbi_link": "GFP: 
mCherry: 
PD-L1: 919
CD80: 941"
  },
  {
    "caption": "A. DG-75 B cells expressing CD80GFP  or  CD86GFP (green) and PD-L1mCherry (red) were incubated with Jurkat  cells (nuclei  shown in grey) expressing CTLA-4  WT or mutant  CTLA-4 Del36 for the indicated durations and analysed by  confocal microscopy. 2 hours prior to assay endpoint, APC-labelled  PD-1  Ig (0.75µg/ml) was added. CD80/CD86  and PD-L1 co-localisation  at the immune synapse is shown in yellow with PD-1 Ig binding  shown in purple. Scale bar, 10µm.",
    "ncbi_link": "CTLA-4: 1493"
  },
  {
    "caption": "B.  Flow cytometry plots of CD80GFP levels on DG-75 B-cells (gated on CTFR+ cells) at 24h with graphical representation of the MFI in each condition (RH graph). The Jreg  cells used, and the anti-PD-1 status is indicated above the plot. C. Flow cytometry  plots of CD28  levels indicating contact between the CD80+ APC  and the PD-1+ CD28+ responder Jurkat T-cells, following CD80 transendocytosis. Graphical representation of the CD28  MFI in each condition is shown on the right. D.  Flow cytometry of CD69  levels on responder Jurkat T-cells and graphical representation of CD69  MFI in each condition. E. Flow cytometry  of CD69  levels on  CD28KO (PD-1+) responder Jurkat T-cells and graphical representation of the CD69+ cells MFI in each condition. Cartoons on the left of B-E illustrate the cell type analysed. Data information: Data is representative of 3 independent experiments showing mean ± SEM. *P≤0.05, **P≤0.01, ns - not significant: two-way ANOVA with Tukey's multiple comparisons test.",
    "ncbi_link": "CD28: 940"
  },
  {
    "caption": "B. Titration  of Abatacept staining  (left hand panel) and EC50  values of Abatacept  (right hand panel) for CD80  only or PD-L1/CD80  co-expressing  DG-75. Data information: Data is representative of 3 independent experiments showing mean ± SEM. *P≤0.05, **P≤0.01, ns - not significant: paired t-test (B)",
    "ncbi_link": "PD-L1: 919
CD80: 941"
  },
  {
    "caption": "A. Total lipids were extracted from PfCDPK7-KO or 3D7 parasites and separated by HPTLC. After quantification by GC-MS content relative to total fatty acids was determined. Relative abundance of individual  phospholipids  was quantified. Disruption of  PfCDPK7  caused a significant decrease in  PC (mean± SEM, n=3; biological replicates, ***p<0.001, t-test).",
    "ncbi_link": "PfCDPK7: "
  },
  {
    "caption": "E. 3D7 or PfCDPK7-KO parasites were cultured in the presence or absence of 200 μM choline in culture medium. After 3 days,  parasitemia was determined by counting parasites on thin blood  smears (mean± SEM, n=6; biological replicates, *p< 0.05, ***p<0.001, ANOVA).",
    "ncbi_link": "PfCDPK7: "
  },
  {
    "caption": "A-B. 3D7 (A) or parasites overexpressing EK-GFP  (B) were used to prepare protein lysates followed by  immunoprecipitation  using anti-PfCDPK7 or anti-GFP  antibody, respectively. Subsequently, protein lysate or indicated IP  were subjected to Western blotting using anti-PMT (A), anti-GFP (B). PMT was found to  co-IP with PfCDPK7 (A, lane 2) and EK-GFP  with PfCDPK7 (B, lane 3).",
    "ncbi_link": "GFP: 
EK: 810500"
  },
  {
    "caption": "C. 3D7 and PfCDPK7-KO parasites at schizont stage (~40 h) were used for  Western blotting using anti-PMT antisera. Actin served as a loading control. Right panel: Densitometry was performed for bands corresponding to PMT in Western blots and the measurements were normalized to  Actin. Fold change in  PMT  was determined with respect to  3D7 (mean± SEM, n=4; biological replicates, **p<0.01, t-test).",
    "ncbi_link": "PfCDPK7: "
  },
  {
    "caption": "A. Parasites overexpressing  EK-GFP or its S37A mutant were synchronized and parasitemia was determined at the end of first (48 h.p.i) and second cycle (96 h.p.i). Fold change in  parasitemia of EK_S37A parasites with respect to WT EK overexpressing parasites was compared, which was significantly reduced (mean± SEM, n=3; biological replicates, *p<0.05, ANOVA).",
    "ncbi_link": "GFP: 
EK: 810500"
  },
  {
    "caption": "C. IFA was performed on parasites expressing WT  EK-GFP  or its S37A mutant 6-12h post-invasion to detect (i) RAP1, which is transferred to  PV post invasion, and (ii) MSP1 which is located at the  PVM. Parasite expressing WT  EK-GFP exhibited typical round ring like shape. In contrast, several parasites expressing the S37A mutant exhibited irregular morphology  with much smaller vacuolar space and in some parasites RAP1  was found outside the  PV (Scale bar-1 μm).",
    "ncbi_link": "GFP: 
EK: 810500"
  },
  {
    "caption": "E. Parasites EK-GFP  or its S37A mutant were synchronized and parasites were allowed to mature to schizonts/segmentors. The graph shows average number of merozoites per schizont  from three biological replicates. Each replicate represents an average of merozoites from 30-40 schizonts. (mean± SEM, n=3; biological replicates, *p<0.05, t-test).",
    "ncbi_link": "GFP: 
EK: 810500"
  },
  {
    "caption": "C-D. UCT943  and MMV048 treated 3D7 (C) or EK-GFP overexpressing parasites (D) were subjected to Western blotting using anti-PMT (C) and anti-GFP (D) antibodies (left panels). Right Panels:  densitometry  was performed for bands corresponding to  PMT (C) or EK-GFP (D), which were normalized with respect to Actin. Fold change in PMT or  EK was determined with respect to DMSO treated parasites (Mean± SEM, n=4; biological replicates, *p<0.05, ***p<0.001, ANOVA).",
    "ncbi_link": "GFP: 
EK: 810500"
  },
  {
    "caption": "D. Trophozoite stage infected erythrocytes were incubated with FM4-64 and DAPI  to assess lipid uptake by 3D7  or PfCDPK7-KO parasites. Subsequently, FM4-64  associated fluorescence was visualized by live microscopy (top panel) and also analyzed by FACS  and % change in FM4-64 uptake in KO parasites was determined (bottom panel) (mean± SEM, n=3; biological replicates, *p<0.05, t-test; Scale bar-1 μm).",
    "ncbi_link": "PfCDPK7: "
  },
  {
    "caption": "Apoptosis levels in cultured control (Cnt) and Atg12cKO HSCs and GMPs (n = 3). Results are expressed as percent caspase activation compared to +cytokines Cnt HSCs (100%).",
    "ncbi_link": "Atg12: 67526"
  },
  {
    "caption": "Absolute number of HSCs in fed and starved Cnt and Atg12cKO mice (n = 4-8 mice per group). Results are expressed as percent of HSCs in fed mice. Data are means ± s.d. Hatching indicates starved conditions. *P ≤ 0.05, **P ≤ 0.01.",
    "ncbi_link": "Atg12: 67526"
  },
  {
    "caption": "b, c, qRT-PCR analyses of pro-autophagic genes in WT (b) and FoxO3a−/− (c) HSCs (n = 3). Results are expressed as log2 fold expression compared to WT GMPs (b) or FoxO3a+/+ HSCs (c) (set to 0).",
    "ncbi_link": "FoxO3a: 56484"
  },
  {
    "caption": "Autophagy flux in cultured FoxO3a−/−::Gfp-Lc3 HSCs (n = 3). Results are expressed as percent GFP-LC3 MFI in -BafA vs. +BafA conditions, and normalized to FoxO3a+/+−::Gfp-Lc3 HSCs. Data are means ± s.d. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.",
    "ncbi_link": "FoxO3a: 56484"
  },
  {
    "caption": "B Expression (cells) and secretion  (media) of VgrG1 from  V. parahaemolyticus RIMD 2210633 derivative POR1  (Vpara; T6SS1+) and its T6SS1- mutant (Vpara/∆hcp1), and from  V. natriegens  (Vnat) carrying the indicated plasmids. Samples were treated (+) or not (-) with 20 µM phenamil  to activate surface sensing in media containing 3% NaCl at 30 °C for 5 h. Loading control (LC) is shown for total protein lysates. Arrows denote bands corresponding to VgrG1. Asterisks denote non-specific bands detected in  Vnat samples.",
    "ncbi_link": "hcp1: 1188694"
  },
  {
    "caption": "C  Expression (cells) and secretion  (media) of  VgrG1  from V. natriegens containing an arabinose-inducible vp1407 in the  chromosomal dns  locus (VnatReg) and harboring an empty plasmid (pEmpty) or plasmids containing VpT6SS1 that lacks vp1407 (pT6SS1Ind) or both vp1407  and hcp1 (pT6SS1Ind/∆hcp1;  T6SS-). Samples were grown in media containing 3% NaCl and either supplemented (+) or not (-) with 0.1%  arabinose  (Ara) at 30 °C. Loading control (LC) is shown for total protein lysates.",
    "ncbi_link": "vp1407: 
hcp1: 1188694"
  },
  {
    "caption": "Viability counts of  V. natriegens  (cyan), V. vulnificus (purple), A. jandaei ∆tssB (brown),  E. coli  (green), and S. enterica (gray) prey before (0 h) and after (4 h) co-incubation with VnatReg attackers (yellow) harboring the indicated plasmids, on media containing 3% NaCl  at 28 °C. The left panels show prey survival when competing alone (single prey) against the attacker at a 4:1 (attacker:prey) ratio; the right panels show the results of a competition experiment in which all prey were mixed together with the attacker at a 10:1:1:1:1:1 (attacker:prey) ratio. Data are shown as the mean ± SD, n = 3 technical replicates. Statistical significance between samples at the 4 h  timepoint  by an unpaired, two-tailed Student's t-test is denoted above and is color coded to match the relevant samples. A significant difference was considered as P < 0.05.",
    "ncbi_link": "tssB: 60611154"
  },
  {
    "caption": "A-D (A, B, D) Viability counts of  V. parahaemolyticus RIMD 2210633 ∆hcp1 (A),  V. alginolyticus 12G01 ∆hcp1/∆hcp2 (B), and V. natriegens  (D) prey bacteria before (0 h) and after (4 h) co-incubation with VnatReg attackers harboring the indicated plasmids, on media containing 3% NaCl and 0.1% arabinose at 28 °C. Data are shown as the mean ± SD, n = 3 technical replicates. Statistical significance between samples at the 4 h  timepoint by an unpaired, two-tailed Student's t-test is denoted above. A significant difference was considered as P < 0.05. ( C) Illustration summarizing the competitions shown in (A, B). Effector and immunity modules expressed by VnatReg carrying pT6SSEffectorless (yellow) are colored to match the bacterium from which they were derived.",
    "ncbi_link": "hcp1: 
hcp2: 
hcp1: 1188694"
  },
  {
    "caption": "C) Representative immunoblots of brain extracts of wild-type, Ttll1-/- and Ttll7-/- mice. Polyglutamylation  of α-tubulin, detected with polyE and GT335, is specifically lost in Ttll1-/- brain. By contrast, β-tubulin glutamylation, which is specifically detected with β‑monoE, is absent from brains  of Ttll7-/- mice. D) Representative  immunoblots of extracts of wild-type, Ttll1‑/- and Ttll7-/- primary  hippocampal   neurons at DIV4. As in  brain (C), α-tubulin polyglutamylation  is specifically lost in Ttll1-/- neurons, while β-tubulin glutamylation lacks in Ttll7-/- neurons. E ",
    "ncbi_link": "Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "F,G)  Immunocytochemistry of DIV4 primary hippocampal neurons from wild type, Ttll1-/- and Ttll7‑/- mice.  Microtubules in Ttll1-/- cells have reduced levels of polyE signal, indicative of lower α-tubulin polyglutamylation (F), Ttll7‑/- neurons are specifically reduced in  β‑monoE reactivity, indicating the lack of β‑tubulin glutamylation (G).",
    "ncbi_link": "Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "A) Representative histology images of cerebella from 3-months-old mice stained with anti-calbindin antibody, which specifically labels Purkinje cells (Sequier et al, 1988). Note the presence of an intact Purkinje-cell layer in cerebella of wild-type, Ttll1-/-, Ttll7-/- and Ccp1-/-Ttll1-/- mice, in contrast to the complete absence of these cells in Ccp1-/- and Ccp1-/-Ttll7-/- mice.",
    "ncbi_link": "Ccp1: 67269
Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "B) Histology  of 25-day old  mice  with partial degeneration of Purkinje Cells. Note that both, Ccp1-/- and  Ccp1-/-Ttll7-/- brains, show highly similar pattern of partial Purkinje-cell loss (red arrow heads: gaps in the Purkinje-cell layer, indicating degenerated Purkinje cells; orange arrow heads: swellings of Purkinje-cell axons, indicative of ongoing degeneration).",
    "ncbi_link": "Ccp1: 67269
Ttll7: 70892"
  },
  {
    "caption": "C) Representative  immunoblots of cerebellum extracts of wild-type, Ccp1-/-, Ttll7-/-, Ccp1-/-Ttll7-/-, Ttll1-/- and Ccp1-/-Ttll1-/- mice. Loss of CCP1 leads to  hyperglutamylation  of α- and β-tubulin as revealed with polyE and  GT335  antibodies. Concomitant deletion of TTLL7 lead to a loss of glutamylation from  β-tubulin (β‑monoE, GT335), while hyperglutamylation  of α-tubulin persists (polyE, GT335). Concomitant loss of CCP1 and TTLL1 eliminates hyperglutamylation from both, α- and β-tubulin (polyE, GT335), while β-tubulin glutamylation is unaltered (β-monoE).",
    "ncbi_link": "Ccp1: 67269
CCP1: 67269
Ttll1: 319953
TTLL1: 319953
Ttll7: 70892
TTLL7: 70892"
  },
  {
    "caption": "Semi-thin cross sections of   femoral quadriceps nerves stained with  alkaline methylene blue. Note the smaller size of Ccp1-/- and Ccp1-/-Ttll7-/- nerves (A).",
    "ncbi_link": "Ccp1: 67269
Ttll7: 70892"
  },
  {
    "caption": "Semi-thin cross sections of  femoral quadriceps nerves stained with  alkaline methylene blue. These sections were quantified for (B) number of myelinated axons, (C) nerve  area, (D) nerve perimeter (Fig. EV2) of  femoral quadriceps nerves from wild-type, Ccp1-/-, Ttll7-/-, Ccp1-/-Ttll7-/-, Ttll1-/- and Ccp1-/-Ttll1-/- mice. Scatter dot plots in which each point represents one nerve of an individual mouse are shown. The black lines indicate means ±SEM. Significance was tested with one-way ANOVA and Holm-Šídák's multiple comparisons test. Note that all three parameters are decreased for Ccp1-/- and Ccp1-/-Ttll7‑/- mice, while Ccp1-/-Ttll1-/- mice showed no difference to the Ttll1-/- control.",
    "ncbi_link": "Ccp1: 67269
Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "E,F) Representative electron microscopy images of cross sections of  femoral quadriceps nerves. (E) Nerves from Ttll1-/- and Ccp1-/-Ttll1-/- mice show no abnormalities of myelinated axons  (green asterisks), indicating that loss of TTLL1  prevents axonal  degeneration caused by the absence of CCP1. (F) Ccp1-/- and Ccp1-/-Ttll7-/- mice both show the presence of foamy macrophages  (magenta arrowheads), which are signs for myelin phagocytosis during  axon  degeneration. This indicates that loss of  TTLL7 cannot prevent the  CCP1-induced degeneration of femoral quadriceps nerves.",
    "ncbi_link": "Ccp1: 67269
CCP1: 67269
Ttll1: 319953
TTLL1: 319953
Ttll7: 70892
TTLL7: 70892"
  },
  {
    "caption": "A) Representative  images of DIV4 primary  hippocampal neurons from wild type, Ttll1-/- and  Ttll7-/- mice Cells were incubated with MitoTracker® (black dots) and mitochondria movements were recorded in the longest neurite  (orange lines).",
    "ncbi_link": "Ttll1: 319953
Ttll7: 70892"
  },
  {
    "caption": "A Gene targeting strategy. Left: max genomic locus, targeting construct and max targeted locus. In vitro Flipase (Flip) deletion of the selectable markers lacZ and neo results in a max targeted locus with exons 4 and 5 (coding for bHLHLZip domain) flanked by two loxP sites (fl, flox allele). Arrows represent PCR primers used for genotyping MaxF9 and MaxF10. Right: genomic PCR analysis of tail DNA from F1 mice. PCR products of max wt (430 bp) and max flox (526 bp) alleles. M, 1kb ladder.",
    "ncbi_link": "neo: 
lacZ: 945006
max: 17187
Max: 17187"
  },
  {
    "caption": "Flow cytometry analyses of B cell populations (GFP+) in Bone Marrow (BM) and spleen. Single-cell suspensions were prepared from BM or spleen of MaxKO-mb1, MycKO-mb1, DKO-mb1 or heterozygous HET-mb1 control mice, stained with antibodies against the indicated markers, and analyzed by flow cytometry. For BM analysis, cells were isolated from femora and tibiae. Pro-B cells (Ly-6c-CD49b-B220+IgM-CD43+), pre-B cells (Ly-6c-CD49b-B220+IgM-CD43-), immature B cells (Ly-6c-CD49b-B220loIgM+CD43-), and mature B cells (Ly-6c-CD49b-B220hiIgM+CD43-) To identify KO cells (GFP+) all the plots show gated GFP+ B lymphocytes.",
    "ncbi_link": "mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "Flow cytometry analyses of B cell populations (GFP+) in Bone Marrow (BM) Single-cell suspensions were prepared from BM of MaxKO-mb1, MycKO-mb1, DKO-mb1 or heterozygous HET-mb1 control mice, stained with antibodies against the indicated markers, and analyzed by flow cytometry. For BM analysis, cells were isolated from femora and tibiae. Pro-B cells (Ly-6c-CD49b-B220+IgM-CD43+), pre-B cells (Ly-6c-CD49b-B220+IgM-CD43-)",
    "ncbi_link": "mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "Flow cytometry analyses of B cell populations (GFP+) in spleen. Single-cell suspensions were prepared from spleen of MaxKO-mb1, MycKO-mb1, DKO-mb1 or heterozygous HET-mb1 control mice, stained with antibodies against the indicated markers, and analyzed by flow cytometry. spleen follicular B cells (B220+CD23+CD21int), marginal zone B cells (B220+CD23-CD21hi) and immature (newly formed/transitional stage 1) B cells (B220+CD23-CD21lo). To identify KO cells (GFP+) all the plots show gated GFP+ B lymphocytes.",
    "ncbi_link": "mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "F, G, H Absolute numbers of B lymphocytes in Bone Marrow (F, G) and spleen (F, H) from MaxKO-mb1 (n=6), MycKO-mb-1 (n=3), DKO-mb1 (n=5) and control HET-mb1 (n=4) mice. Columns represent mean values and error bars standard deviations. *p<0.05, **p<0.01, ***p<0.001. The different B cell populations were identified by flow cytometry Experiment representative of at least three independent experiments.",
    "ncbi_link": "mb-1: 14999
mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "I Cell cycle analysis by flow cytometry of sorted GFP+ pre- and pro-B (B220+IgM-), immature (B220loIgM+) and mature (B220hiIgM+) bone marrow B cells from MaxKO-mb1, MycKO-mb1, DKO-mb1 and HET-mb1 control mice. Mice (n=5) were injected (i.p.) with 200 µg of EdU and analyzed 4 h later. Single-cell suspensions were prepared, stained and sorted. Sorted cells were subsequently stained with propidium iodide for DNA content. Experiment representative of at least three independent experiments. Dotted line is shown for EdU MFI comparison.",
    "ncbi_link": "mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "J Percentage of annexin-V+GFP+ cells in the BM of MaxKO-mb1(n=5), MycKO-mb1(n=3), DKO-mb1 (n=3) and control (n=4) mice. Pro-B, pre-B, immature and mature B lymphocyte subpopulations were identified by flow cytometry as indicated in E. *p<0.05, ***p<0.001. Experiment representative of at least three independent experiments.",
    "ncbi_link": "mb1: 14999
Max: 17187
Myc: 17869"
  },
  {
    "caption": "Flow cytometry analysis and absolute numbers of B220loCD138+ (plasmablasts) (A, B) from HET-cd19 (n=6), MaxKO-cd19 (n=8), MycKO-cd19 (n=4), and DKO-cd19 (n=5) mice. Spleen B220+GFP+ B lymphocytes were sorted and activated in vitro with LPS plus IL-4 for 72 h. Cells were stained with monoclonal antibodies against the indicated markers and analyzed by flow cytometry. *p<0.05, **p<0.01. Columns represent mean values and error bars standard deviations. Experiment representative of at least three independent experiments.",
    "ncbi_link": "GFP: 
cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "Flow cytometry analysis and absolute numbers of B220+IgG1+ switched B cells (C, D) from HET-cd19 (n=6), MaxKO-cd19 (n=8), MycKO-cd19 (n=4), and DKO-cd19 (n=5) mice. Spleen B220+GFP+ B lymphocytes were sorted and activated in vitro with LPS plus IL-4 for 72 h. Cells were stained with monoclonal antibodies against the indicated markers and analyzed by flow cytometry. *p<0.05, **p<0.01. Columns represent mean values and error bars standard deviations. Experiment representative of at least three independent experiments.",
    "ncbi_link": "cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "I Analysis of germinal center (GC) formation in the spleen of MaxKO-cd19, Myc-KO-cd19, DKO-cd19 and heterozygous control mice immunized with TNP-KLH. Representative images of frozen spleen sections stained with IgM (grey/blue), PNA (GC marker; red), and GFP (Max-, c-Myc- or c-Myc/Max-deficient B cells; green). Scale bar, 80µm.",
    "ncbi_link": "cd19: 12478
Max: 17187
c-Myc: 17869
Myc: 17869"
  },
  {
    "caption": "J Upper, Number of GCs per mouse in spleen sections of immunized MaxKO-cd19 (n=3 mice, n=186 follicles analyzed), MycKO-cd19 (n=3 mice, n=178 follicles analyzed), DKO-cd19 (n=3 mice, n=191 follicles analyzed) and heterozygous control mice (n=3 mice, n=203 follicles analyzed). Lower, Frequencies of GC (PNA+) GFP+ (deleted cells) or GFP- (non-deleted cells) in immunized MaxKO-cd19 (n=13 GCs), MycKO-cd19 (n=21 GCs), DKO-cd19 (n=27 GCs) and heterozygous control (n=62 GCs) mice. Analysis was performed at 13 days post-immunization. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "A Number of cell divisions in activated mature B lymphocytes. Sorted B220+GFP+ spleen cells from HET-cd19 (n=5), MaxKO-cd19 (n=5), MycKO-cd19 (n=3), and DKO-cd19 (n=3) mice were stained with a cell tracer, activated in vitro with LPS plus IL-4 for 72 h and analyzed by flow cytometry. Experiment representative of at least three independent experiments B Cell counts from the cultures C Photographs of B cell cultures Scale bar, 500 µm. 4× magnification. D Forward scatter (FSC) histograms of activated B lymphocytes An arbitrary dashed line is shown for comparison.",
    "ncbi_link": "cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "Cell cycle analysis of sorted B220+GFP+ B lymphocytes activated in vitro. Cells were activated and EdU was added 4 h before harvesting. Cells were stained with propidium iodide to measure DNA content. Experiment representative of at least three independent experiments. An arbitrary dashed line shows the difference of EdU MFI. S phase mean fluorescence intensity (MFI): 7871 HET, 6512 MaxKO, 5860 MycKO, 6420 DKO",
    "ncbi_link": "Max: 17187
Myc: 17869"
  },
  {
    "caption": "A Bar plot showing the number of DEGs (adj. p-value <0.01, FC +1.5 in red, 1.5 < FC >-1.5 in white, FC< -1.5 in blue). Sorted B220+GFP+ spleen B cells from MaxKO-cd19, MycKO-cd19, DKO-cd19 and control HET-cd19 mice were activated with LPS plus IL-4 for 72 h and analyzed. Two samples for each condition were used.",
    "ncbi_link": "cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "D Venn diagrams of up- (left) and down-regulated genes (right) for all three conditions (+/-1.5-FC and p<0.01). Heatmaps of genes only deregulated in MaxKO-cd19, MycKO-cd19, or DKO-cd19 mice are shown.",
    "ncbi_link": "cd19: 12478
Max: 17187
Myc: 17869"
  },
  {
    "caption": "C qPCR analysis of up- and down-regulated genes Pooled RNA was prepared from sorted B220+GFP+ spleen B cells of MaxKO-cd19 (n=4), MycKO-cd19 (n=4), or DKO-cd19 (n=4) and control HET-cd19 (n=4) mice activated Genes were randomly selected and qPCR was performed using specific primers for cd72, med13l, card11, ssh2, cdc7, mrpl12, rpl39, and cysc. max and c-myc were included as controls and actin was used for normalization.",
    "ncbi_link": "actin: 11461
card11: 108723
cd19: 12478
cd72: 12517
cdc7: 12545
cysc: 13063
Max: 17187
max: 17187
med13l: 76199
mrpl12: 56282
c-myc: 17869
Myc: 17869
rpl39: 67248
ssh2: 237860"
  },
  {
    "caption": "Immunoblots of acyl-biotin exchange purifications from Hela cells transiently transfected with WT Golga7b or a palmitoylation-deficient mutant form of the protein with cysteines replaced with alanine residues. The hydroxylamine sensitivity of the Golga7b signal in the + HA condition of the WT pull-down and not in either the - HA condition or the + HA condition of the mutant shows that Golga7b is a palmitoylated protein.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Immunoblots of acyl-biotin exchange purifications from Hela cells treated with either DHHC5 siRNA or control non-targeting siRNA.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "Immunoblots showing rescue of Golga7b palmitoylation in DHHC5 depleted cells after transfection of WT DHHC5 but not by the DHHC5 catalytic mutant.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "A significant reduction in the Golga7b signal is observed in the + HA condition of the pull-down when DHHC5 is depleted with siRNA. The graph displays mean +/- s.e.m. N=4, *=p<0.05, paired t-test.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "Tagged constructs with palmitoylation site mutations in DHHC5 and Golga7b were expressed in in HeLa cells depleted of endogenous DHHC5. Confocal images of HeLa cells co-expressing WT Golga7b (1st column) and DHHC5 (2nd column), with a merged image (3rd column). Confocal images of HeLa cells co-expressing palmitoylation deficient mutant Golga7b (1st column) and DHHC5 (2nd column), with a merged image (3rd column). Confocal images of HeLa cells co-expressing WT Golga7b (1st column) and the catalytic mutant DHHS5 (2nd column), with a merged image (3rd column). Confocal images of HeLa cells co-expressing palmitoylation deficient mutant Golga7b (1st column) and DHHS5 (2nd column), with a merged image (3rd column). Confocal images of HeLa cells co-expressing WT Golga7b (1st column) and DHHC5 C-terminal palmitoylation deficient mutant (2nd column), with a merged image (3rd column). Confocal images of HeLa cells co-expressing palmitoylation deficient mutant Golga7b (1st column) and DHHC5 C-terminal palmitoylation deficient mutant (2nd column), with a merged image (3rd column). Quantification of the plasma membrane signal of DHHC5 in each of the images (A-F), the graph displays mean +/- s.e.m. ****=p<0.001, n.s. = not significant, unpaired t-test. N=35, DHHC5 + WT Golga7b. N=41, DHHC5 + mutant Golga7b. N=35, DHHS5 + WT Golga7b. N=31, DHHS5 + Golga7b mutant. N=29, C-terminal mutant + WT Golga7b. N=30, C-terminal mutant + mutant Golga7b. Co expression of palmitoylation-deficient mutant Golga7b significantly reduces DHHC5 as well as DHHCS5 signal at the plasma membrane. The majority of the DHHC5 C-terminal palmitoylation-deficient mutant is localised to the plasma membrane in a Golga7b independent manner. All N numbers refer to the number of cells imaged and quantified, all experiments repeated 4 times. Data information: All images show ectopic protein expression only. All scale bars 10µm.",
    "ncbi_link": "Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "Confocal images of endogenous DHHC5 in HeLa cells expressing FLAG-tagged WT Golga7b. Confocal images of endogenous DHHC5 in HeLa cells expressing FLAG-tagged mutant Golga7b.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Confocal images of endogenous Golga7b and DHHC5 in HeLa cells treated with negative control non-targeting siRNA. Confocal images of endogenous Golga7b and DHHC5 in HeLa cell treated with Golga7b siRNA.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Quantification of plasma membrane signal of endogenous DHHC5 when co-expressed with WT or mutant Golga7b or without any transfected Golga7b. ****=P<0.001, t-test, endogenous + WT Golga7b n=37, endogenous + mutant Golga7b n=23, endogenous n=42. Expression of the palmitoylation deficient mutant Golga7b causes endogenous DHHC5 to be internalised in the cell, while WT Golga7b stabilises DHHC5 at the plasma membrane.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Quantification of the plasma membrane signal of DHHC5 in (C and D), ****=p<0.001 t-test, control siRNA n=23, Golga7b siRNA n=23.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "FLAG-DHHC5 immunoprecipitations were performed using lysates from Hela cells co-expressing either wild-type (WT) or palmitoylation deficient mutant (m) Golga7b. The interaction of DHHC5 with its substrate Flot2 was measured by immunoblotting and is significantly reduced in the presence of palmitoylation deficient mutant Golga7b, quantification normalised to input, *=p<0.05, ratio paired t-test, n=3.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Validation of novel DHHC5 interactors by co-IP: immunoblots of Dsg2from Hela cells co-expressing DHHC5 and either Wild-type (WT) or mutant (m) Golga7b and quantification normalised to input, *=p<0.05, ratio paired t-test, n=3. Co-IP immunoblots of clathrin heavy chain from Hela cells co-expressing DHHC5 and either wild-type (WT) or mutant (m) Golga7b and quantification normalised to input, *=p<0.05, ratio paired t-test, n=3. Co-IP immunoblots of ZO-1 protein from Hela cells co-expressing DHHC5 and either wild-type (WT) or mutant (m) Golga7b and quantification normalised to input, **=p<0.01 ratio paired t-test, n=3.",
    "ncbi_link": "Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "30 minute DMSO treatment of HeLa cells co-expressing WT DHHC5 (FLAG tagged) and mutant Golga7b (HA tagged). 30 minute Dynasore treatment (25µM) of HeLa cells co-expressing WT DHHC5 (FLAG tagged) and mutant Golga7b (HA tagged).",
    "ncbi_link": "FLAG: 
HA: 
Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "Non-targeting control siRNA treatment (10nM) of HeLa cells expressing mutant Golga7b (HA tagged). Images are detecting endogenous DHHC5 and the HA tagged Golga7b AP2µ siRNA treatment (10nM) of HeLa cells that were subsequently transfected with mutant Golga7b (HA tagged). Images are detecting endogenous DHHC5 and the HA tagged Golga7b.",
    "ncbi_link": "HA: 
AP2µ: 1173
Golga7b: 401647"
  },
  {
    "caption": "Biotin endocytosis assays of HeLa cells with endogenous DHHC5, over-expression of DHHC5 alone, co-expression of DHHC5 and WT Golga7b, co-expression of DHHC5 and mutant Golga7b or expression of the DHHC5 C-terminal mutant. Biotinylated cell surface proteins endocytosed within 15 minutes were purified using streptavidin resin and blots probed with an antibody to DHHC5. The lack of signal in the pull-down of the DHHC5 C-terminal mutant or when DHHC5 and WT Golga7b are co-expressed indicates that DHHC5 is stabilised at the plasma membrane in these conditions. The robust signal in the pull-down of endocytosed proteins from cells co-expressing DHHC5 and mutant Golga7b shows a high rate of endocytosis of DHHC5 in this condition. N=3, *=p<0.05, paired t test\"",
    "ncbi_link": "Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "ABE purifications from HeLa cells treated with 10nM non-targeting siRNA (nt siRNA) or DHHC5 siRNA were immunoblotted for Dsg2. Loss of the band in the +HA pull-down in the DHHC5 siRNA condition shows that Dsg2 palmitoylation is dependent on DHHC5.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "Confocal images of DHHC5 and Dsg2 in nt siRNA treated A431 cells three hours after calcium was reintroduced to the media in calcium switch experiments. Confocal images of DHHC5 and Dsg2 in DHHC5 depleted A431 cells three hours after calcium was reintroduced to the media in calcium switch experiments.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "Confocal images of DHHC5, Dsg2 and Golga7b in Golga7b depleted A431 cells three hours after calcium was reintroduced to the media in calcium switch experiments. See Appendix Figure S6 for quantification of data in panels B-D.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Immunoblots and quantification of Dsg2 pulled-down in cell surface biotinylation assays in nt siRNA, DHHC5 siRNA or Golga7b siRNA treated conditions. Quantification of the intensity of the DSG2 signal in the pulldown is normalised to input. A significant reduction of cell surface Dsg2 occurs when DHHC5 or Golga7b are depleted by siRNA. *=",
    "ncbi_link": "Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "10x brightfield images of A431 cells treated with non-targeting siRNA at time 0 (left) and after 48 hours (right) of 5 ng/ml EGF treatment. 10x brightfield images of A431 cells treated with DHHC5 siRNA at time 0 (left) and after 48 hours (right) of 5ng/ml EGF treatment. Quantification of cell scattering of A431 cells, showing a significant increase in cell scatter after 48 hours of DHHC5 knockdown and therefore a decrease in cell adhesion was observed.",
    "ncbi_link": "DHHC5: 25921"
  },
  {
    "caption": "10x brightfield images of A431 cells treated with non-targeting siRNA at time 0 (left) and after 48 hours (right) of 5ng/ml EGF treatment. 10x brightfield images of A431 cells treated with Golga7b siRNA at time 0 (left) and after 48 hours (right) of 5ng/ml EGF treatment. Quantification of cell scattering of A431 cells, showing a significant increase in cell scatter after 48 hours of Golga7b knockdown and therefore a decrease in cell adhesion, was observed.",
    "ncbi_link": "Golga7b: 401647"
  },
  {
    "caption": "Plot showing the resistance of A431 cells from a trans-epithelial electrical resistance assay treated with either DHHC5 siRNA, Golga7b siRNA or non-targeting siRNA. A significant reduction in TEER demonstrates a decrease in cell adhesion after both DHHC5 and Golga7b depletion.",
    "ncbi_link": "Golga7b: 401647
DHHC5: 25921"
  },
  {
    "caption": "(c) 2,3,5-triphenyltetrazolium chloride-stained brain sections showing the infarct area in WT and H3R−/− mice receiving saline, the H3R antagonists A331440, clobenpropit (CLOB) and thioperamide, (THIO; 5 mg kg−1, i.p., immediately at reperfusion and 6 h later), and the H3R agonist immepip (IMME, 1 μg, i.c.v., at reperfusion) after I/R (1 h MCAO followed by 24 h reperfusion; scale bar, 5 mm).",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(b,d) H3R was inhibited by thioperamide, and cleaved caspase-3 protein expression is shown by western blot in WT and H3R−/−mice after tMCAO (b) (n=6-7 per condition; **P0.01, ***P0.001 with analysis of variances (ANOVAs) followed by Bonferroni/Dunn post hoc test)",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(b,d) H3R was inhibited by thioperamide, and cleaved caspase-3 protein expression is shown by western blot in WT and H3R−/−mice in cultured neurons subjected to OGD/R (d) (n=8 per condition; *P0.05, ***P0.001 with ANOVAs followed by the Bonferroni/Dunn post hoc test). Data are presented as mean±s.e.m. Full-size blots are shown in Supplementary Fig. 10.",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(a) 2,3,5-Triphenyltetrazolium chloride (TTC)-stained brain sections from WT and HDC−/− mice showing the infarct area in those receiving saline, the H3R antagonist thioperamide (THIO), the H1R antagonist pyrilamine (PYRI; 10 mg kg−1, i.p., at reperfusion), the H2R antagonist cimetidine (CIME; 10 mg kg−1, i.p., at reperfusion) and α-FMH (50 mg kg−1, i.p., 2 h before ischemia) after 24 h reperfusion (n=6 per condition; scale bar, 5 mm).",
    "ncbi_link": "HDC: 15186"
  },
  {
    "caption": "(b) Representative western blots showing the phosphorylation of Akt/GSK-3β/mTOR/P70S6K signaling in H3R−/− mice after OGD/R injury. The digits below represent the semiquantified optidensity of the bands, the control bands were defined as 1.00.",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(a) Representative immunohistochemical staining of LC3 (green) along with NeuN staining (red) in WT and H3R−/− mice (scale bar, 25 μm).",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(b,c) When thioperamide was administered in vivo, LC3 expression was assessed by western blot after I/R in WT mice (b) (*P0.05, ***P0.001; n=6 mice per condition, with analysis of variances (ANOVAs) followed by the Bonferroni/Dunn post hoc test), and in H3R−/− mice (c) (***P0.001 versus H3R−/− sham group; n=5-6 mice per condition, with ANOVAs followed by the Bonferroni/Dunn post hoc test.) Data are presented as mean±s.e.m. Full-size blots are shown in Supplementary Fig. 12.",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(b) TTC-stained sections showing the infarct area after administration of 3-MA (100 nmol, i.c.v., at reperfusion) in WT and H3R−/− mice (scale bar, 5 mm), and (c) bar graph showing infarct volume (n=6-8 mice per condition; *P0.05, ***P0.001, with analysis of variances (ANOVAs) followed by the Bonferroni/Dunn post hoc test).",
    "ncbi_link": "H3R: 99296"
  },
  {
    "caption": "(d) TTC-stained sections (scale bar, 5 mm) and bar graph showing the infarct area after administration of thioperamide in Atg5+/−mice (n=4-6 mice per condition).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) In cultured neurons, viability was tested by MTT after siRNA for Atg7 and OGD/R (n=7 per condition; ***P0.001, with ANOVAs followed by the Bonferroni/Dunn post hoc test).",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(g) Viability was tested by MTT assay on Atg5+/+and Atg5−/− MEFs after thioperamide administration after OGD/R (n=7 per condition; **P0.01, ***P0.001, with ANOVAs followed by the Bonferroni/Dunn post hoc test). Data are presented as mean±s.e.m.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(e) Western blots showing the effect of siRNA for CLIC4 on phosphorylation of Akt/GSK-3β/mTOR/P70S6K signalling and LC3 expression in OGD/R. Full-size blots are shown in Supplementary Fig. 14.",
    "ncbi_link": "CLIC4: 29876"
  },
  {
    "caption": "(f) Representative western blots and bar graph showing the expression of LC3-I and LC3-II on steady-state autophagy and autophagic flux under OGD/R when CLIC4 was knocked down (data are presented as mean±s.e.m.; n=6; *P0.05, **P0.01; , with ANOVAs followed by the Bonferroni/Dunn post hoc test). Full-size blots are shown in Supplementary Fig. 14.",
    "ncbi_link": "CLIC4: 29876"
  },
  {
    "caption": "(g) Cell viability was assessed by MTT assay after siRNA for CLIC4 under OGD/R (data are presented as mean±s.e.m.; n=8 per condition; ***P0.001, with ANOVAs followed by the Bonferroni/Dunn post hoc test).",
    "ncbi_link": "CLIC4: 29876"
  },
  {
    "caption": "Fate of Purkinje cells in mice with Purkinje-cell-specific knockout of Ccp1. Ccp1flox/flox L7-cre mice show a massive but incomplete degeneration of Purkinje cells (calbindin-stained; red) at 4 months, while all Purkinje cells are degenerated at 18 months. Scale bar: 500 µm.",
    "ncbi_link": "Ccp1: 67269
cre: 2777477
L7: 18545"
  },
  {
    "caption": "Fate of Purkinje cells in mice with combinatorial knockout alleles. Knockout of Ccp1 (pcd-mouse; Ccp1-/-) results in a complete degeneration of Purkinje cells (calbindin-stained; red), while the additional knockout of Ttll1 selectively in the Purkinje cells (L7-cre) protects the entire Purkinje cell layer from degeneration up to 18 months. Scale bar: 500 µm.",
    "ncbi_link": "Ccp1: 67269
cre: 2777477
L7: 18545
Ttll1: 319953"
  },
  {
    "caption": "Nissl staining of the Purkinje cell layer of the brains from various knockout mice shown in (C) confirms the absence of Purkinje cells in Ccp1-/-, and the presence of a wild-type-like Purkinje-cell density in Ccp1-/- Ttll1flox/flox L7-cre mice. Scale bar: 20 µm. Purkinje cell layer (PC) and granule cell layer (GC) are indicated.",
    "ncbi_link": "Ccp1: 67269
cre: 2777477
L7: 18545
Ttll1: 319953"
  },
  {
    "caption": "Immunoblot of tissue extracts from cerebella of Ttll1-/- and wild type mice, probed with the polyE, anti-∆2-tubulin and 12G10 antibodies. Increasing amounts of extracts were loaded for detection of polyglutamylated proteins with polyE.",
    "ncbi_link": "Ttll1: 319953"
  },
  {
    "caption": "Analyses of tubulin polyglutamylation (antibody: polyE) in extracts of different brain regions of wild type, Ccp1-/-, Ccp6-/- and Ccp1-/-Ccp6-/- mice with immunoblot. In 3-weeks old mice, hyperglutamylation is observed in cerebral cortex, cerebellum and hippocampus of Ccp1-/- and Ccp1-/-Ccp6-/- mice. In 2- and 5-month-old mice, hyperglutamylation is restricted to the cerebellum in Ccp1-/- mice, however it persists in all three brain regions of the Ccp1-/-Ccp6-/- mice (complete analysis in Fig. EV1; α- and β-tubulin bands indicated).",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Nissl-stained frontal sections of wild type, Ccp1-/-, Ccp6-/- and Ccp1-/-Ccp6-/- mice at 1 and 5 months, showing age-dependent thinning (arrow heads) of the cortex in Ccp1-/-Ccp6-/- mice (complete analysis in Appendix Fig. S2A).",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Quantification of the thickness of motor and somatosensory cortex of 1- and 5-month-old mice shown in Appendix Fig. S2. The single values shown in Appendix Fig. S2B were averaged, and values from each genotype-specific group were tested against the average values of the remaining three genotypes (Appendix Fig. S2C). Only the cortical thickness of 5-month-old Ccp1-/-Ccp6-/- mice is significantly decreased (mean ±SEM; Mann-Whitney t-test).",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Immunohistochemistry of brain sections with anti-MAP2 antibody for visualization of neurons (layer V) and apical dendritic (layer IV) and with anti-GFAP for reactive astrocytes (layer V). The complete analysis is shown in Fig. EV2A, EV3A. Scale bars: 50 µm. Quantifications of number of MAP2-positive neurons in layer V, and of number of apical dendrites in layer IV (Fig. EV2B) reveal reduced neuron number in layer V, and reduced dendritic density in layer IV of 5-month-old Ccp1-/-Ccp6-/- mice. Quantification of the number of reactive astrocytes in layer V (Fig. EV3B) shows a significant increase over wild type in Ccp1-/- and in Ccp6-/- mice, however a much stronger increase is seen in Ccp1-/-Ccp6-/- mice. Complete analyses are shown in Fig. EV2C, EV3C (mean ±SEM; student's t-test).",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Immunohistochemistry of brain sections stained with SMI-32 antibody (a representative section of one brain per genotype group is shown, complete analysis in Appendix Fig. S3). Neuronal SMI-32 labelling indicates increased axonal damage in the cortex of Ccp1-/-Ccp6-/- mice at 5 months. Scale bar: 100 µm.",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Representative electron microscopy images of sections of wild type and Ccp1-/-Ccp6-/- cerebral cortices with myelinated axons. In Ccp1-/-Ccp6-/- sections, several myelinated axons show signs of degeneration, such as accumulation of cellular organelles and cytoplasmic densification (arrows), or axonal lysis (stars). Note that only some axons in the observed sections displayed these phenotypes Ccp1-/-Ccp6-/-, while such figures were never observed in wild type cortices. Scale bar: 1 µm.",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Fate of Purkinje cells in 1-month-old wild type, spastin-/-, Ccp1-/- and Ccp1-/-spastin-/- mice visualized with anti-calbindin antibody. Ccp1-/- and Ccp1-/-spastin-/- mice show almost complete loss of the Purkinje-cell layer. Scale bar: 500 µm.",
    "ncbi_link": "Ccp1: 67269
spastin: 50850"
  },
  {
    "caption": "Nissl staining shows the complete loss of Purkinje cells in Ccp1-/- and Ccp1-/-spastin-/- mice. Scale bar: 20 µm. Purkinje cell layer (PC) and granule cell layer (GC) are indicated.",
    "ncbi_link": "Ccp1: 67269
spastin: 50850"
  },
  {
    "caption": "Calbindin staining of sections showing axons of Purkinje cells as in (A). While wild type and spastin-/- show normal axons, Ccp1-/- and Ccp1-/-spastin-/- mice show axonal swellings (arrow heads) in the remaining Purkinje cells. Scale bars: 20 µm.",
    "ncbi_link": "Ccp1: 67269
spastin: 50850"
  },
  {
    "caption": "Immunoblot of cell extracts from Ccp1flox/floxCcp6flox/flox hippocampal neurons without, or after transduction with lentivirus expressing either GFP or GFP-2A-cre after 4 days in culture. Note the specific increase of polyglutamylation (polyE) in neurons transduced with GFP-2A-cre lentivirus.",
    "ncbi_link": "GFP: 
Ccp6: 78933
Ccp1: 67269
cre: 2777477"
  },
  {
    "caption": "All kymographs of one representative set of experiments. Mitochondria movements (Movie S1) were plotted in kymographs and analyzed as described in (A). Scale bars: 60 sec, 20 µm. Analyses of (D) run length and (E) speed distribution, represented as scatter dot plots with each point representing a single run extracted from the kymographs shown in (C). Each group represents the pool of measurement of multiple neurons made in the experiment. The black line indicates the median of the distribution with whiskers at interquartile range. Numerical value of the medians is indicated below each plot. (F) Overall motility of mitochondria represented as fraction of time mitochondria spent in movement relative to the total number of mitochondria during the recording time of 60 s. Values (below plots) from one set of experiment (C) show a decrease of about 50% in Ccp1-/-Ccp6-/- conditions, while (G) mitochondria density is unaltered. (H-K) Statistical analyses of mitochondria transport parameters of experiments shown in (D-G; Fig. EV4A-D). Each bar represents the mean (±SEM) of medians of single experiments for run length (H) and speed (I) distributions, and average (±SEM) mitochondria motility (J) and density (K) of all seven experimental sets. Values of fold change between control and Ccp1-/-Ccp6-/- conditions are indicated below the graphs. Green bars are for anterograde, and red for retrograde transport events. Significance was tested using unpaired t-test. Average run length (H) as well as speed (I) showed no significant differences in these two parameters between control and Ccp1-/-Ccp6-/- conditions. (J) The average of overall motility reveals an about 50% decrease in overall mitochondria motility, while mitochondria density (K) is unaltered between control and Ccp1-/-Ccp6-/- conditions.",
    "ncbi_link": "Ccp6: 78933
Ccp1: 67269"
  },
  {
    "caption": "Parental HCT116 cells expressing a stable tetracycline-inducible shRNA against IMPDH2 (IM2iKD) and either a stable inducible non-targeting (NT) shRNA (IM2iKD-shNT) or an shRNA targeting IMPDH1 (IM2iKD - shIM1), were grown for 7 days in the absence or presence of doxycycline (2 µg/mL) (- dox or + dox, respectively). mRNAs of IMPDH1 and IMPDH2 were quantified by real-time qPCR in 2 independent experiments carried out in triplicate and normalized to β-actin mRNA (C). Data information: data are presented as relative to control. *p<0.05, **p<0.01, ***p<0.001 by two tail T-Student's test.",
    "ncbi_link": "β-actin: 60
IM1: 3614
IMPDH1: 3614
IM2: 3615
IMPDH2: 3615"
  },
  {
    "caption": "Parental HCT116 cells expressing a stable tetracycline-inducible shRNA against IMPDH2 (IM2iKD) and either a stable inducible non-targeting (NT) shRNA (IM2iKD-shNT) or an shRNA targeting IMPDH1 (IM2iKD - shIM1), were grown for 7 days in the absence or presence of doxycycline (2 µg/mL) (- dox or + dox, respectively). Whole cell extracts were analyzed on Western blots with the indicated antibodies. GAPDH was used as a loading control. Quantification of band intensity of p53 and p21 is shown. Mean ± SD is representative of four independent experiments. (right panel) (D). Data information: data are presented as relative to control. *p<0.05, **p<0.01, ***p<0.001 by two tail T-Student's test.",
    "ncbi_link": "IM1: 3614
IMPDH1: 3614
IM2: 3615
IMPDH2: 3615"
  },
  {
    "caption": "A, HCT116 cells were transfected with either a NT or a siRNA against RPL11 for 24 hrs and treated with the vehicle alone (-) or the indicated concentration of MPA for 24 hrs. The levels of p53 and p21 were analyzed on Western blots. GAPDH was used as a loading control. Quantification of band intensity of p53 and p21 of four independent experiments is shown (right panel). Data information: All data are presented as Mean ± SD, relative to control. *p<0.05, **p<0.01, ***p<0.001, by two tail T-Student's test.",
    "ncbi_link": "RPL11: 6135"
  },
  {
    "caption": "C, HCT116 cells were transfected with either a NT siRNA or a siRNA against RPL11 for 24 hrs and were pretreated for 30 mins in the absence (-) or the presence (+) of the combination of 10 µM of the ATR inhibitor VE-821 (ATRi) and 10 µM the ATM inhibitor KU-55933 (ATMi), followed by addition of the vehicle alone (-) or MPA 10 µM for additional 24 hrs. The levels of p53 were analyzed on Western blots. GAPDH was used as a loading control. Quantification of band intensity of p53 of at least two independent experiments is shown (right panel). Data information: All data are presented as Mean ± SD, relative to control. *p<0.05, **p<0.01, ***p<0.001, by two tail T-Student's test.",
    "ncbi_link": "RPL11: 6135"
  },
  {
    "caption": "A, HCT116 cells were treated with either vehicle alone (-), 1 µM MPA, 10 µM MPA or 5 nM ActD for 24 hrs and mRNA levels of p21 were quantified by real-time qPCR in 2 independent experiments carried out in triplicate and normalized to 28S rRNA. Data information: , data are presented as mean ± SD, relative to control. *p<0.05, **p<0.01, ***p<0.001, by two tail T-Student's test.",
    "ncbi_link": "28S rRNA: 
p21: 1026"
  },
  {
    "caption": "B, Autoradiogram (upper panel) and Ethidium Bromide (EtBr)-stained agarose gel (lower panel) of 18S and 28S rRNA from HCT116 cells treated as indicated in the Methods section.",
    "ncbi_link": "18S: 
28S rRNA: "
  },
  {
    "caption": "C, Autoradiogram (upper panel) and EtBr-stained TBE-urea polyacrylamide gel (lower panel) of 5S, 5.8S rRNA and tRNAs in lysates",
    "ncbi_link": "5.8S rRNA: 
5S: "
  },
  {
    "caption": "HCT116 cells were treated for 24 hrs. Cell lysates were collected, subjected to ultracentrifugation, spiked with firefly luciferase mRNA and immunoprecipitated with anti-HDM2 rabbit antibody (IP HDM2) or the IgG control (IgG). D, Levels of HDM2, RPL5, RPL11, and the IP negative control mTOR in the whole cell extract (WCE), the post-ribosomal lysates (INPUT, left panel) and in the HDM2 immunoprecipitated fraction (right panel) were analyzed on Western blots. The results are representative of two independent experiments. Quantification of band intensity of HDM2, RPL5 and RPL11 of at least two independent experiments is shown (lower right panel).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "HCT116 cells were treated for 24 hrs. Cell lysates were collected, subjected to ultracentrifugation, spiked with firefly luciferase mRNA and immunoprecipitated with anti-HDM2 rabbit antibody (IP HDM2) or the IgG control (IgG). E, the Levels of immunoprecipitated 5S rRNA were determined by real time qPCR and normalized to the firefly luciferase mRNA. Data are normalized and presented as relative to untreated cells immunoprecipitated with anti-HDM2. The results are representative of three independent experiments carried out in triplicates. Data information: data are presented as mean ± SD, relative to control. *p<0.05, **p<0.01, ***p<0.001, by two tail T-Student's test.",
    "ncbi_link": "5S rRNA: 
luciferase: "
  },
  {
    "caption": "B, HCT116 p21-/- isogenic cell lines were transfected for 24 hrs with an empty plasmid (EV) or a plasmid encoding a p21wt cDNA (p21-OE), then cells were serum-deprived for 16 hrs before the re-addition of serum for additional 24 hrs in absence or presence of 10 µM MPA. Cells were subjected to p21 immunolabeling, propidium iodide staining and FACS analysis. The results are representative of two independent experiments.",
    "ncbi_link": "p21: 1026"
  },
  {
    "caption": "B, HCT116 cells transfected with a NT siRNA or a siRNA against RPL11 for 24 hrs were treated with 10 µM MPA for additional 72 hrs. The levels of γ-H2AX were analyzed on Western blots. GAPDH was used as a loading control.",
    "ncbi_link": "RPL11: 6135"
  },
  {
    "caption": "A stable inducible HEK-293T cell line expressing myc-PP2AC  (panel A were treated with DMSO, 20 μM  DT-061 or 2 μM iHAP1  for 2 hours and myc-PP2AC affinity purified, respectively. The binding  of the indicated proteins was analysed by  Western blotting A) representative of 3 independent experiments",
    "ncbi_link": "myc: 
PP2AC: 5516///5515"
  },
  {
    "caption": "A stable inducible  HEK-293T cell line expressing myc-PP2AC  (panel B) were treated with DMSO, 20 μM DT-061 or 2 μM iHAP1  for 2 hours and myc-PP2AC  by quantitative mass spectrometry (B). B) analysis of a biological triplicate.",
    "ncbi_link": "myc: 
PP2AC: 5516///5515"
  },
  {
    "caption": "a stable inducible HeLa  cell line expressing myc- PP2R1A  (C) were treated with DMSO, 20 μM  DT-061 or 2 μM iHAP1 for 2 hours and myc-PP2R1A affinity purified, respectively. The binding  of the indicated proteins was analysed by Western blotting C) representative of 2 technical repeats",
    "ncbi_link": "myc: 
PP2R1A: 5518"
  },
  {
    "caption": "E) Doxycyclin-inducible CRISPR-Cas9 HeLa  cell lines allow for depletion of specific B56 subunits. Growth assays in the presence of the indicated concentrations of  DT-061  or iHAP1  measured after 12 days of treatment. Mean and SD of three independent experiments are shown.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935"
  },
  {
    "caption": "A) Schematic of the experimental setup and results of CRISPR  screen. Genes were ranked based on their normZ score. The top hits which were further analysed are highlighted.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "B) Validation of CRISPR  screen results using RNAi depletion followed by SRB growth assay. Cells were treated with DMSO  (Ctr) or DT-061  5.5 µM or iHAP1  0.5 µM. C) Incucyte growth assay after RNAi depletion of indicated proteins alone or in combination with DMSO  or 5.5 μM  DT-061  or 0.5 μM iHAP1  treatment. Data information: B-C) Mean and SD of three independent experiments is shown.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "F RT-qPCR of several mechanosensitive proteins (TGFB1, NFKB1, EGR1, and RUNX2) and of four mechanoreceptors (ITGB1, ITGB3, ITGAV and ITGA2) in PC and surrounding soft tissue at E60 and after culturing for two days with (3 kPa) or without extra mechanical stress (0 kPa). n = 3 for each group. Data represent the means ± SEM. One-way ANOVA (Newman-Keuls test for post-hoc comparisons between two groups), *P < .05, **P < .01, ***P < .001; NS, not significant. =",
    "ncbi_link": "EGR1: 100520726
ITGA2: 397483
ITGAV: 397285
ITGB1: 397019
ITGB3: 397063
NFKB1: 751869
RUNX2: 100737965
TGFB1: 397078"
  },
  {
    "caption": "A-C H&E staining of miniature pig canine frontal sections from embryonic day 60 (E60 group) (A) and after the mandible slices were infected with RUNX2 overexpression lentiviral vector with a Myc tag (overexpression group) (B) or overexpression control lentiviral vector with a Myc tag (O-control group) (C); (A'-C') are magnifications of boxed regions in the corresponding figure panels. Data information: Data represent the means ± SEM. n = 3 for all experiments. Scale bars = 50 µm",
    "ncbi_link": "Myc: 
RUNX2: 100737965"
  },
  {
    "caption": "L, M IF staining of RUNX2 expression after infecting mandible slices with scrambled shRNA lentiviral vector (knockdown control, K-control) (L) or RUNX2 shRNA lentiviral vector (knockdown) (M); (L'-M') are magnifications of boxed regions in the corresponding figure panels. Data information: Data represent the means ± SEM. n = 3 for all experiments. Scale bars = 50 µm (other panels).",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "O, P FISH of β-catenin in mandible slices infected with RUNX2 shRNA lentivirus (knockdown) or scrambled shRNA lentivirus (scramsh) via RNAscope. Data information: Scale bars = 50 µm.",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "A, B IF of Lef1 in mandible slices at embryonic day 60 (E60) infected with RUNX2 overexpression lentiviral vector (overexpression) or overexpression control lentiviral vector (O-control). (A'-B') are magnifications of boxed regions in the corresponding figure panels. Dashed lines mark the epithelium of PC. C Relative IF expression levels of Lef1 in epithelium (Epi.) and mesenchyme (Mes.) of the overexpression and O-control groups. Data information: Data represent the means ± SEM. Scale bars = 100 µm. n = 3 for all experiments. Unpaired t-tests for C , **P < .01, ***P < .001; NS. not significant.",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "G Western blots of Lef1, non-phospho-β-catenin, and RUNX2 after DFCs were infected with control lentiviral vector or RUNX2 overexpression lentiviral vector. (G') Relative expression levels between control vector and RUNX2 overexpression groups. Data information: Data represent the means ± SEM. Unpaired t-tests , *P < .05, **P < .01, ***P < .001; NS. not significant.",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "H Western blots of Lef1, non-phospho-β-catenin, and RUNX2 after DFCs were infected with scrambled shRNA (scramsh) or RUNX2 knockdown shRNA (knockdown) lentiviral vectors. (H') Relative expression levels between scramsh and knockdown groups.",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "I Western blots of nuclear non-phospho-β-catenin and Lamin B in DFCs of RUNX2 overexpression (O), control vector (V), RUNX2 knockdown (K), scramsh (S), compressed force (F; 1.0 g/cm2), and control (C; 0 g/cm2) groups. Sample were loaded in a gradient (7.5, 15, 30, and 60 μg) showing a linear relationship for each group.",
    "ncbi_link": "RUNX2: 100737965"
  },
  {
    "caption": "A) To detect CHN-1 and UFD-2, indicated lysates of young adult worms were subjected to immunoblotting with anti-CHN-1 and anti-UFD-2 antibodies. Tubulin served as a loading control. Right, quantification of the CHN-1 signals normalized to tubulin levels and plotted as N2 (wild-type; black), ufd-2(tm1380) (cyan), and UFD-2P951A (magenta). Plotted data are the mean of three biological replicates.",
    "ncbi_link": "CHN-1: 172303
ufd-2: 174295"
  },
  {
    "caption": "B) CHN-1 protein levels were determined in the indicated lysates of young adult worms treated with a proteasome inhibitor (MG-132, 10µM) and DUB inhibitor (NEM, 100mM). Tubulin served as a loading control. Right, quantification of the CHN-1 signals normalized to tubulin levels plotted as control (black), or MG-132 treated (magenta) in N2 (wild-type) and ufd-2(tm1380). Plotted data are the mean of three biological replicates.",
    "ncbi_link": "ufd-2: 174295"
  },
  {
    "caption": "C) Protein level of endogenous AHCY-1 in N2 (wild-type), chn-1(by155), CHN-1 OE, and ufd-2(tm1380) young adult worms treated with the proteasome inhibitor (MG-132, 10 µM) and DUB inhibitor (NEM, 100 mM). Protein samples were resolved via SDS-PAGE and immunoblotted with anti-AHCY-1 antibodies. Tubulin served as a loading control. Right, quantification of the modified AHCY-1 signals plotted as Ub-modified AHCY-1 species normalized to unmodified endogenous AHCY-1 signal and plotted for N2 (wild-type; black), chn-1(by155) (magenta), CHN-1 OE (yellow), and ufd-2(tm1380) (cyan). Plotted data are the mean of three biological replicates.",
    "ncbi_link": "chn-1: 172303
CHN-1: 172303
ufd-2: 174295"
  },
  {
    "caption": "D) Representative images of GFP::AHCY-1 fluorescence in chn-1(by155), ufd-2(tm1380), and CHN-1 OE background. Scale bar = 200µm. Below, quantification of the AHCY-1 GFP signal plotted as fluorescence intensity for GFP::AHCY-1 expressing worms (control; black), chn-1(by155) (magenta), ufd-2(tm1380) (cyan) or CHN-1 OE (yellow). Plotted data are the mean of three biological replicates.",
    "ncbi_link": "chn-1: 172303
CHN-1: 172303
ufd-2: 174295"
  },
  {
    "caption": "A Representative image of tumor-bearing mice and tumors after subcutaneous injection of Hepa1-6 hepatoma cells into WT and Tet2-/- (KO) mice.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "B Mean tumor volumes in WT and Tet2-/- mice (n=6).",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "A, B Immunohistochemistry analysis of CD8a, CD4 (A), PCNA, and Foxp3 (B) in tumors from WT and Tet2-/- (KO) mice subcutaneously injected with Hepa1-6 hepatoma cells. Corresponding bar charts display positive staining, quantified using Image Pro Plus 6.0 software (n=3). Pictures were captured at 400X magnification. Scale bar = 50 μm.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "A Percentages of MDSCs (CD11b+Gr1+) gated from the CD45+ cell population in peripheral blood and spleen [n=11, tumor-free (-) WT and Tet2-/-（KO） mice; n=12, tumor-bearing (+) WT and KO mice, peripheral blood; n=10, tumor-free (-) WT and KO mice; n=13, tumor-bearing (+) WT and KO mice, spleen]. B Percentages of G-MDSCs (CD11b+Ly6G+) gated from the CD45+ cell population in peripheral blood and spleen [n=14, tumor-free (-) WT and KO mice; n=15, tumor-bearing (+) WT and KO mice, peripheral blood; n=15, tumor-free (-) WT and KO mice; n=15, tumor-bearing (+) WT and KO mice, spleen]. C Percentages of M-MDSCs (CD11b+Ly6C+) gated from the CD45+ cell population in peripheral blood and spleen [n=5, tumor-free (-) WT and KO mice; n=6, tumor-bearing (+) WT and KO mice, peripheral blood; n=6, tumor-free (-) WT and KO mice; n=6, tumor-bearing (+) WT and KO mice, spleen]. ",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "E Percentages of CD8+ T cells gated from the CD45+ cell population in peripheral blood and spleen [n=11, tumor-free (-) WT and KO mice; n=5, tumor-bearing (+) WT and Tet2-/- KO mice, peripheral blood; n=16, tumor-free (-) WT and KO mice; n=12, tumor-bearing (+) WT and KO mice, spleen]. F Percentages of CD4+ T cells gated from the CD45+ cell population in peripheral blood and spleen [n=8, tumor-free (-) WT and KO mice; n=5, tumor-bearing (+) WT and KO mice, peripheral blood; n=16, tumor-free (-) WT and KO mice; n=11, tumor-bearing (+) WT and KO mice, spleen]. ",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "A Sorting efficiency of G-MDSCs (CD11b+Ly6G+) from spleens of tumor-bearing Tet2-/- （KO） and WT mice.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "C G-MDSCs purified from spleen of tumor-bearing WT or Tet2-/- mice were co-cultured with CD8+ T cells at the indicated cellular ratios for T cell activation assays, quantified by CFSE-labeling and dye dilution for 3 days in vitro. Representative histograms show CFSE signals in the in vitro T cell activation assays. D Quantification of CD8+ T cell proliferation in panel C. Each point represents a co-culture experiment (n=3). ns, not significant. Graphs show mean ± SEM and statistical analysis by Student's t-test. ",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "B Representative flow cytometry plots of splenic G-MDSCs measured in tumor-free untreated Tet2-/- (KO) and WT mice and after anti-Ly6g or PBS injections into tumor-bearing mice. Flow cytometric analysis of T cells in Tet2-/- mice and littermate control mice (WT) with or without anti-Ly6g treatment after tumor challenge.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "E Percentages of CD8+ T cells from the spleens of tumor-bearing mice with or without anti-mouse Ly6g treatment [n=17, PBS (-) injected tumor-bearing WT and KO mice; n=6, anti-Ly6g (+) antibody injected tumor-bearing WT and KO mice]. F Percentages of CD4+ T cells from the spleens of tumor-bearing mice with or without anti-mouse Ly6g treatment [n=16, PBS (-) injected tumor-bearing WT and KO mice; n=6, anti-Ly6g (+) antibody injected tumor-bearing WT and KO mice Flow cytometric analysis of T cells in Tet2-/- mice and littermate control mice (WT) with or without anti-Ly6g treatment after tumor challenge.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "A Gene set enrichment analysis of the IL-6/JAK/STAT signaling pathway in G-MDSCs from tumor-bearing Tet2-/- (KO) versus WT mice (n=2). p-value was calculated by permutation.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "E, F Percentages of CD11b+ Ly6G+ G-MDSCs gated from total cells in (E) spleen and (F) peripheral blood from tumor-bearing mice treated with PBS or anti-mouse IL-6 antibody [n=5, PBS (-) injected tumor-bearing WT and KO mice; n=4, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, spleen; n=4, PBS (-) injected tumor-bearing WT and KO mice; n=4, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, peripheral blood]. G, H Percentages of CD8+ T cells gated from total cells in (G) spleen and (H) peripheral blood from tumor-bearing mice treated with PBS or anti-mouse IL-6 [n=5, PBS (-) injected tumor-bearing WT and KO mice; n=5, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, spleen; n=5, PBS (-) injected tumor-bearing WT and KO mice; n=5, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, peripheral blood]. I, J Percentages of CD4+ T cells gated from total cells in (I) spleen and (J) peripheral blood from tumor-bearing mice treated with PBS or anti-mouse IL-6 [n=5, PBS (-) injected tumor-bearing WT and KO mice; n=5, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, spleen; n=4, PBS (-) injected tumor-bearing WT and KO mice; n=5, anti-IL-6 antibody (+) injected tumor-bearing WT and KO mice, peripheral blood]. Flow cytometric analysis of G-MDSCs and T cells in Tet2-/- mice and littermate control mice (WT) with or without anti-IL-6 treatment after tumor challenge.",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "A. Western blot analysis of the IFT22RNAi+GFP::IFT22S19N cell line probed with the anti-IFT22 antibody (bottom) and with an anti-paraflagellar rod (PFR) as loading control (top).",
    "ncbi_link": "GFP: 
IFT22: 3664573"
  },
  {
    "caption": "C. Kymographs showing the movement of the GFP::IFT22S19N in the presence (left) or the absence (right) of the IFT22 endogenous protein. Note the improved signal-to-noise ratio in the absence of endogenous IFT22. P and D mark the proximal and distal ends of the flagellum, respectively. Scale bars are 5 seconds (time, vertical) and 5 µm (length, horizontal)",
    "ncbi_link": "IFT22: 3664573"
  },
  {
    "caption": "A. Western blot analysis of the IFT22RNAi+GFP::IFT22A86R cell line probed with the anti-IFT22 antibody (bottom) and with an anti-BiP as loading control (top).",
    "ncbi_link": "GFP: 
IFT22: 3664573"
  },
  {
    "caption": "B. IFA with the indicated cell lines using the mAb25 (marker for the axoneme, central panels) and an anti-IFT172 antibody (marker for IFT, bottom panels). The top panels show the phase contrast images merged with DAPI (cyan) that stains nuclear and mitochondrial DNA. The arrowheads indicate the presence of short flagella stained with the Mab25 antibody in the IFT22RNAi cells. Scale bars correspond to 5 µm.",
    "ncbi_link": "IFT22: 3664573"
  },
  {
    "caption": "C. Sections of IFT22RNAi+GFP::IFT22rescue (top panels) or IFT22RNAi+GFP::IFT22A86R cells (bottom panels) were analysed by transmission electron microscopy. Sections through the flagellar pocket, the transition zone and the flagellum are shown. Scale bars are 500 nm (flagellar pocket sections) or 200 nm (transition zone and flagellum sections). The white arrow indicates an endocytic vesicle budding off the flagellar pocket whereas the black one points at an IFT train. (Axo = axoneme, TZ = transition zone, BB = basal body)",
    "ncbi_link": "GFP: 
IFT22: 3664573"
  },
  {
    "caption": "A. Hematoxylin and eosin staining of 5-micron thick testis sections of adult control, Plk1 cHet, and Plk1 cKO mice. Stars indicate examples of spermatocytes with condensed chromosomes. B. Percent testis to body weight ratios from control (n = 8), Plk1 cHet (n = 4), and Plk1 cKO (n = 7) adult mice.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "C. TUNEL staining of paraffin embedded testis sections of adult control, Plk1 cHet, and Plk1 cKO mice. D. The number of TUNEL positive cells per seminiferous tubule cross-section was quantified in control Plk1 cHet, and Plk1 cKO mice. Two technical replicates were performed per genotype, and 100 seminiferous tubule cross sections were analyzed per replicate.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "E. Hematoxylin and eosin staining of 5-micron thick testis sections of adult control, Aurka cHet, and Aurka cKO mice. Stars indicate examples of spermatocytes with condensed chromosomes. F. Percent testis to body weight ratios from control (n = 5), Aurka cHet (n = 3), and Aurka cKO (n = 5) adult mice.",
    "ncbi_link": "Aurka: 20878"
  },
  {
    "caption": "G. TUNEL staining of paraffin embedded testis sections of adult control, Aurka cHet, and Aurka cKO mice. H. The number of TUNEL positive cells per seminiferous tubule cross-section was quantified in control Aurka cHet, and Aurka cKO mice. Two technical replicates were performed per genotype, and 100 seminiferous tubule cross sections were analyzed per replicate.",
    "ncbi_link": "Aurka: 20878"
  },
  {
    "caption": "I. Representative images of spermatocytes containing monopolar, bipolar, and multipolar spindles immunolabeled against alpha-tubulin (red), centromere (green), and stained with DAPI. J. Spindle pole number per primary spermatocyte was quantified for control, Aurka cKO, Plk1 cHet, and Plk1 cKO. n = 3 experimental replicates with > 40 metaphase I spermatocytes analyzed per genotype in each experiment.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "B. The percent of centrioles containing CEP164 distal appendages was quantified from three biological replicates (n = 30 total cells) in control, Aurka cKO, Plk1 cHet, and Plk1 cKO spermatocytes at the pachytene-stage of meiotic prophase and metaphase I.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "C. Quantification of gamma-tubulin positive centrosomes per metaphase I spermatocyte. Immunolabeling was performed on three biological replicates, with ≥20 spermatocytes quantified per replicate. The total number of cells quantified for control, Aurka cKO, Plk1 cHet, and Plk1 cKO mice were 137, 169, 198, and 198, respectively.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "D. Spermatocytes were immunolabeled against gamma-tubulin (green), alpha-tubulin (red), and stained with DAPI (blue). Plk1 and Aurka cKO spermatocytes arrest at a prometaphase stage. Scale bars = 5 μm.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "Western blots of gamma-tubulin from protein extracts obtained from 19dpp and 22dpp control, Aurka cKO, and Plk1 cKO spermatocytes (E). Total protein stained with 2,2,2-Trichloroethanol (TCE) display protein loading.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "Western blots of gamma-tubulin from Protein extracts from control and Plk1 cHet spermatocytes at 16, 19 and 22 dpp (F). Total protein stained with 2,2,2-Trichloroethanol (TCE) display protein loading.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "B. Quantification of TACC3 positive centrosomes per metaphase I spermatocyte. Immunolabeling was performed on three biological replicates, with ≥20 spermatocytes quantified per replicate. The total number of cells quantified for control, Aurka cKO, Plk1 cHet, and Plk1 cKO mice were 97, 103, 96, and 105, respectively.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "Western blots of TACC3 from protein extracts obtained from 19dpp and 22dpp control, Aurka cKO, and Plk1 cKO spermatocytes (D). Total protein stained with 2,2,2-Trichloroethanol (TCE) display protein loading.",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "Western blots of TACC3 from Protein extracts from control and Plk1 cHet spermatocytes at 16, 19 and 22 dpp (C). Total protein stained with 2,2,2-Trichloroethanol (TCE) display protein loading.",
    "ncbi_link": "Plk1: 18817"
  },
  {
    "caption": "E, F. Spermatocytes were immunolabeled against beta-catenin (green), SYCP3 (red), PCNT (magenta), and stained with DAPI (blue). Middle columns emphasize beta-catenin signal in diplonema and diakinesis spermatocytes. Scale bars = 5 μm. G. Quantification of beta-catenin positive centrosomes per spermatocyte at diakinesis. Immunolabeling was performed on three biological replicates, with ≥20 spermatocytes quantified per replicate. The total number of cells quantified for control, Aurka cKO, Plk1 cHet, and Plk1 cKO mice were 89, 106, 122, and 93, respectively. ",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "C. Centrosome (PCNT) separation was assessed in Aurka; Plk1 dKO spermatocytes. Three biological replicates were analyzed with > 30 metaphase I spermatocytes assessed per replicate using the four centrosome separation classifications",
    "ncbi_link": "Aurka: 20878
Plk1: 18817"
  },
  {
    "caption": "A BreastMark microarray platform; Kaplan-Meier curves of overall survival (OS), demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+ breast cancer. A log rank test was used to calculate P=2.8 e-07 (n= 934, number of events= 216).",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "C BreastMark microarray platform; correlation of ESRP1 expression with overall survival in tamoxifen-treated patients. A log rank test was used to calculate P=1.218, e-06 (n= 210, number of events= 49).",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "D BreastMark microarray platform; correlation of ESRP1 expression with overall survival in chemotherapy-treated patients. A log rank test was used to calculate the P=0.28 (n= 129, number of events= 21)",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "E The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER+ breast cancer, demonstrating that high expression of ESRP1 (red line) is associated with poor prognosis in ER+. A log rank test was used to calculate P=0.00011 (n= 656, number of events= 62).",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "F The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) RNA-seq dataset; Kaplan-Meier curves of overall survival (OS) in ER- breast cancer. Red-high ESRP1 expression; Black-low ESRP1 expression. A log rank test was used to calculate P=0.19 (n=100, number of events=17).",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "A RT-qPCR confirmed the stable knockdown of ESRP1 expression in endocrine-resistant cells using a shRNA lentiviral system (Mission TRC human shRNA constructs-Sigma); 2-control (LCC2 cells transduced with pLKO.1 control vector) and 2C1 and 2C3 (LCC2 cells transduced with pLKO.1 shRNA ESRP1). Clones were selected for expression verification (clone 1 and clone 3); 9-control (LCC9 cells transduced with pLKO.1 control vector), 9C2 and 9C3 (LCC9 cells transduced with pLKO.1 shRNA ESRP1. Clones were selected for expression verification (clone 2 and clone 3). * represents P <0.05; statistically significant. Data (mean ± SD) were calculated using two-way ANOVA based on three independent biological replicates.",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "E Impact of ESRP1 knockdown on in vivo tumor growth. Five million cells (2-control, 2C3, 9-control and 9C2) were implanted into mammary fat pads of athymic mice (five mice per group) in the presence of supplemental estrogen. Tumors were measured weekly using calipers for external measurements. Tumor volume was calculated as L x W2/2, where L is length and W is width (note the different scale for tumor volumes). Data (mean ± SD) were calculated using two-way ANOVA (n= 5 mice per group).",
    "ncbi_link": "ESRP1: 207920"
  },
  {
    "caption": "C-D Protein expression of key EMT-TFs in ESRP1 knockdown cells (2C3 and 9C2) compared to endocrine resistant control cell lines (2-control and 9-control) using Western blotting analysis.",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "E Protein expression of key EMT-TFs in ESRP1 knockdown cells (T-47D-kESRP1) and ESRP1-overexpressing MCF-7 cells compared to their control counterparts (T-47D-control and MCF-7-control, respectively).",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "A Doughnut chart for RNA-seq analysis showing the differentially regulated alternative splicing events (ASEs) and their corresponding genes in ESRP1 knockdown cells compared to control cells; SE: skipped exon, RI: retained intron, MXE: mutually exclusive exons, A5SS: alternative 5' splice site, and A3SS: alternative 3' splice site). The \"percent spliced in\" (PSI or ψ) value was estimated. Differences in inclusion levels (∆ψ) between samples and their significance were calculated (P<0.05 and IΔψI>0.1). Circle 1: all ASEs; Circle 2: all genes corresponding to all ASEs; Circle 3: significant ASEs; Circle 4: significant genes corresponding to significantly altered ASEs; Circle 5: significant ASEs with ESRP1 motifs; Circle 6: significant genes corresponding to significantly altered ASEs with ESRP1 motifs. ESRP-binding motifs were obtained from Dittmar et al.31[] and analyzed based on the following assumption: the presence of the motif in the downstream region of an exon results in inclusion of the exon, while upstream or intraexonic location leads to exclusion of the exon. ",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "B Radar plot showing that the EMT gene signature was not altered at the gene level in the ESRP1 knockdown model (LCC2 set). C Radar plot showing that the EMT gene signature was altered at the ASEs level (SE) in the ESRP1 knockdown model (LCC2 set). ",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "D Radar plot showing that the EMT gene signature was not altered at the gene level in the ESRP1 knockdown model (LCC9 set). E Radar plots showing that the EMT gene signature was altered at the ASEs level (SE) in the ESRP1 knockdown model (LCC9 set). ",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "C Validation of the protein levels of FASN, SCD1 and PHGDH protein levels in ESRP1 knockdown versus control resistant cell lines using Western blot analysis. GAPDH was used as the loading control. The data are representative of three individual biological replicates.",
    "ncbi_link": "ESRP1: 54845"
  },
  {
    "caption": "A Representative images of E18.5 coronal cortical sections from Kcc2lox/lox embryos electroporated in utero at E14.5 with plasmids encoding EGFP, EGFP+Cre (Cre) or EGFP+Cre+KCC2FL (Cre+KCC2FL). DAPI staining (blue) marks cell nuclei. UCP, upper cortical plate; LCP, lower cortical plate; Sp, subplate; IZ, intermediate zone. Scale bar: 50 µm. B Quantification of the number of EGFP+ neurons/ROI from embryos electroporated with constructs in (A). Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, **P < 0.01. Data are presented as mean ± S.E.M., n (EGFP) = 8 embryos; n (Cre) = 8 embryos; n (Cre+KCC2FL) = 13 embryos. ",
    "ncbi_link": "Cre: 
EGFP: 
Kcc2: 57138
KCC2: 57138"
  },
  {
    "caption": "C Representative image of cleaved Caspase 3 (Cas-3, upper panel) and TUNEL (lower panel) staining in coronal sections from Kcc2lox/lox cortex at E16.5 electroporated with EGFP or EGFP+Cre are shown. Arrowheads point to neurons expressing Cas-3 (upper panel) and TUNEL (lower panel). DAPI staining (blue) marks cell nuclei. CP, cortical plate; VZ, ventricular zone; SVZ, subventricular zone; Sp, subplate; IZ, intermediate zone. Large scale bar: 50 µm, small scale bar: 20 µm. D Quantification of the percentage of EGFP+ neurons expressing apoptotic markers at E16.5 from embryos electroporated with EGFP ± Cre. Statistical significance was determined using Mann-Whitney U test (Cas-3); and two-tailed t test (TUNEL), ***P < 0.001. Data are presented as mean ± S.E.M., n (-Cre) = 6 embryos; n (+Cre) = 6 embryos. E The number of EGFP+Cre neurons as a percentage of neurons expressing EGFP alone. Statistical significance was determined using a two-tailed Student's t test. Data are presented as mean ± S.E.M., n = 6 embryos. ",
    "ncbi_link": "Cre: 
EGFP: 
Kcc2: 57138"
  },
  {
    "caption": "A Top: Representative images of E18.5 coronal cortical brain sections from Kcc2lox/lox embryos electroporated in utero at E14.5 together with plasmid constructs encoding Cre, a fluorescent marker (EGFP or mRFP, both pseudo-colored in green) and one of the following constructs: KCC2ΔNTD, KCC2CTD, KCC2R952H, or cofilinS3A. DAPI staining (blue) marks cell nuclei. UCP, upper cortical plate; LCP, lower cortical plate; Sp, subplate; IZ, intermediate zone. Scale bar: 50 µm. Bottom: schematic representation of the KCC2 constructs. B Quantification of the number of transfected neurons/ROI from embryos electroporated with constructs in (A). The mean number of transfected neurons from embryos electroporated with Cre+KCC2FL taken from Fig 1B shown as dotted line. Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, **P < 0.01 to Cre+KCC2FL. Data are presented as mean ± S.E.M., n (KCC2ΔNTD) = 7 embryos; n (Cre+KCC2CTD) = 9 embryos; n (Cre+KCC2R952H) = 9 embryos; n (Cre+cofilinS3A) = 8 embryos. ",
    "ncbi_link": "Cre: 
cofilin: 12631
Kcc2: 57138
KCC2: 57138"
  },
  {
    "caption": "A Representative image of E18.5 coronal cortical sections stained for layer V marker Ctip2 (red) from Kcc2lox/lox embryos electroporated in utero at E14.5 with plasmid constructs encoding EGFP or EGFP+Cre (Cre). Upper boundary of layer V indicted with dotted line. EGFP signal is shown as green pseudocolor. DAPI staining (blue) marks cell nuclei. Sp, subplate; IZ, intermediate zone. Scale bar = 50 µm. B Number of EGFP+Cre neurons migrating above (II-IV) and below (V-VI/IZ-SVZ) the upper border of layer V normalized to respective data from embryos electroporated with EGFP alone. Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, ***P < 0.001 to EGFP. Data are presented as mean ± S.E.M., n (EGFP +Cre) = 8 embryos; n (EGFP) = 8 embryos.",
    "ncbi_link": "Cre: 
EGFP: 
Kcc2: 57138"
  },
  {
    "caption": "C Representative image of E18.5 coronal brain sections stained for layer V marker Ctip2 (red) from Kcc2lox/lox embryos electroporated in utero at E14.5 with plasmid constructs encoding mRFP or mRFP+Cre (Cre). Upper boundary of layer V indicted with dotted line. Sp, subplate; IZ, intermediate zone. Scale bar = 50 µm. mRFP signal is shown as green pseudocolor. DAPI staining (blue) marks cell nuclei. D Number of mRFP+Cre neurons migrating above (II-IV) and below (V-VI/IZ-SVZ) the upper border of layer V normalized to respective data from embryos electroporated with mRFP alone. Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, ***P < 0.001 to mRFP. Data are presented as mean ± S.E.M., n (mRFP+Cre) = 5 embryos; n (mRFP) = 5 embryos. ",
    "ncbi_link": "Cre: 
mRFP: 
Kcc2: 57138"
  },
  {
    "caption": "E Representative image of E18.5 coronal cortical sections stained for layer V marker Ctip2 (red) from Kcc2lox/lox embryos co-electroporated in utero at E14.5 with plasmids encoding a fluorescent marker (green) together and Cre+KCC2FL, Cre+KCC2CTD, or Cre+KCC2R952H. DAPI staining (blue) marks cell nuclei. Upper boundary of layer V indicted with dotted line. Sp, subplate; IZ, intermediate zone. Scale bar = 50 µm. F Number of transfected neurons migrating above (II-IV, left) and below (V-VI/IZ-SVZ, right) the upper border of layer V in embryos electroporated with constructs in (E) normalized to respective data from embryos electroporated with Cre. Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, *P < 0.05, **P < 0.01, ***P < 0.001 to Cre. Data are presented as mean ± S.E.M., n (Cre+KCC2FL) = 13 embryos; n (Cre+KCC2CTD) = 9 embryos; n (Cre+KCC2R952H) = 9 embryos. ",
    "ncbi_link": "Cre: 
Kcc2: 57138
KCC2: 57138"
  },
  {
    "caption": "A, B, C The layer thickness and neuronal number within each layer was assessed using layer-specific markers in Kcc2-/-and Kcc2+/+ embryos at E18.5. Cux1 was used to label layers II-IV (A), Ctip2 to label layer V (B), and Tbr1 to label layer VI (C). Dashed white lines in the representative images in (A-C) indicate upper and lower layer boundaries. Sp, subplate. Statistical significance was determined using Kruskal-Wallis test with Dunn's post hoc (neuronal numbers) and one-way ANOVA with Holm-Sidak's post hoc (layer thickness). Data are presented as mean ± S.E.M., n = 11 embryos for both genotypes. Scale bar = 50 µm.",
    "ncbi_link": "Kcc2: 57138"
  },
  {
    "caption": "D Representative image of E18.5 coronal cortical sections stained for layer V marker Ctip2 (red) in Kcc2-/- and Kcc2+/+ embryos electroporated in utero at E14.5 with a plasmid encoding EGFP (green). DAPI staining (blue) marks cell nuclei. Upper boundary of layer V indicted with dotted line. Sp, subplate; IZ, intermediate zone. Scale bar = 50 µm. E Neurons from the brain sections in (D) were quantified and the total number of EGFP+ neurons in the Kcc2-/- sections is presented as a percentage of pooled Kcc2+/+ and Kcc2+/- values. Statistical significance was determined using one-tailed Student's t test, *P < 0.05. Data are presented as mean ± S.E.M., n (Kcc2+/+ + Kcc2+/-) = 14 embryos; n (Kcc2-/-) = 9 embryos. F Number of EGFP+ neurons in Kcc2-/- embryos migrating above (II-IV) and below (V-VI/IZ-SVZ) the upper border of layer V normalized to respective pooled data from Kcc2+/+ and Kcc2+/- embryos. Statistical significance was determined using one-way ANOVA with Holm-Sidak's post hoc test, **P < 0.01 to Kcc2+/+ + Kcc2+/-. Data are presented as mean ± S.E.M., n (Kcc2+/+ + Kcc2+/-) = 14 embryos; n (Kcc2-/-) = 9 embryos. ",
    "ncbi_link": "Kcc2: 57138"
  },
  {
    "caption": "D) In the 6 months old p32cKO heart, p62 and multi-ubiquitin staining patterns were co-localized. Scale bar, 5 µm. E) In the 6 months old p32cKO heart, the staining patterns of p62 and the mitochondrial marker protein, pyruvate dehydrogenase (PDH), were co-localized. Scale bar, 5 µm.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(F) Western blot analysis of ubiquitinated proteins using an anti-multi-ubiquitin antibody in the 6 months old WT and p32cKO heart (n = 4 mice per group). Error bars are presented as mean ± SD. Student's t-test was performed on WT vs p32cKO, ***p < 0.005.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(B) Autofluorescence showing lipofuscin localization around the nucleus in the 6 months old p32cKO heart. Tissues were excited at a wavelength of 540 (upper panel) or 470 (lower panel) and emission spectra were collected with a confocal microscope at wavelengths (band path) of 580-630 nm (upper panel) or 510-560 nm (lower panel). Enlarged view of the white squares is shown right. Scale bars, 20 µm. The quantification of the ratio of autofluorescence of DAPI staining is presented in the plot in the right panel as mean ± SEM (three months old mice, n = 11; 6 months old mice, n = 9-14, 9 months old mice, n = 9-15, 12 months old mice, n = 11-21). Statistical significance was assessed by Student's t-test, ***p < 0.005.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(D) Western blot analysis of Lamp2 in the 6 months old WT and p32cKO hearts. Quantification is shown in the lower panel (n = 4 mice per group). GAPDH was used as an internal control. Error bars are presented as mean ± SD. Student's t-test was performed on WT vs p32cKO, ***p < 0.005.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(A) LC-MS/MS metabolomic analysis of NAD+, NADH, NADP+, nicotinamide and NAAD in the 6 months old WT and p32cKO hearts. NAD+ and NADP+ showed significantly different levels between WT and p32cKO hearts (n = 12). Error bars are presented as mean ± SD. Student's t-test was performed on WT vs p32cKO, **p < 0.001, ***p < 0.0002.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(B) Real-time PCR analysis of RNA expression of NAD-synthesizing enzymes in the 6 months old WT and p32cKO hearts. Error bars are presented as mean ± SD. Student's t-test was performed on WT mice vs p32cKO mice (n = 6), ***p < 0.005, *p < 0.05. The right panel shows the NAD synthesis pathway and mRNA expression levels are indicated by red arrows. NAM: nicotinamide, NA: nicotinic acid, QA: quinolic acid, NMN: nicotinamide mononucleotide.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(G) Nmnat3 mRNA expression in 3T3-L1 cells after 1 mM CAP treatment for 72 h. The HIF1α inhibitor (20 or 50 µM) was added 2 h before the CAP treatment. Error bars are presented as mean ± SD of three independent experiments. Student's t-test was performed on WT cells vs WT cells treated CAP and (or) HIF1α inhibitor,**p < 0.01, *p < 0.05.",
    "ncbi_link": "HIF1α: 15251
Nmnat3: 74080"
  },
  {
    "caption": "(I) Nmnat3 mRNA expression in 3T3-L1 cells after 150 µM CoCl2 treatment for 72 h (n = 3). Error bars are presented as mean ± SD of three independent experiments. Statistical significance was assessed by Student's t-test, **p < 0.01.",
    "ncbi_link": "Nmnat3: 74080"
  },
  {
    "caption": "(A) Lysosomal acidification is impaired in p32KO MEFs. Representative images of WT and p32KO MEFs, stained with dextran-Oregon Green (488) and dextran-TMRM. Scale bar, 5 µm. Addition of 1 mM NMN for 48 h to p32KO MEFs rescued lysosomal acidification, and 1 mM CAP treatment of WT MEFs for 48 h decreased lysosomal acidification. Dextran-Oregon Green is quenched under acidic pH, and thus an increased green:red ratio denotes impaired lysosomal acidification. The average ± SEM of the green:red ratio in at least 30 cells in two independent experiments is presented in the plot (normalized to WT green/red = 1). Statistical significance was assessed by Student's t-test, *p < 0.05, ***p < 0.001.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "(E) Nmnat3(v1) overexpression in p32KO MEFs rescued lysosomal function. LysoTracker Red-stained p32KO MEFs were quantified by flow cytometry. Error bars are presented as mean ± SEM of 4 independent experiments. Statistical significance was assessed by Student's t-test, ***p < 0.001.",
    "ncbi_link": "p32: 12261"
  },
  {
    "caption": "A t-SNE map of combined  scRNA-seq profiles of total cells isolated from pathologically normal preneoplastic tissue from BRCA1 mutation carriers (BRCA1; n=4) and non-BRCA premenopausal  women (n=8) with no family history of breast cancer. Cell colors represent individual samples. B Same t-SNE map as in (A) but colored by cluster (cluster resolution 0.12). C Epithelial clusters were identified by EPCAM expression  and the  non-epithelial cells  were re-clustered to reveal  immune and  stromal cell populations (cluster resolution 0.08). Lineage identity was determined by hierarchical clustering according to top marker genes",
    "ncbi_link": "BRCA: 672
BRCA1: 672
EPCAM: 4072"
  },
  {
    "caption": "D t-SNE plot showing the combined single-cell transcriptomes of total tissue cells from  BRCA1 preneoplastic tissue and TNBCs  (n=4 for each), colored according to individual patients (B1 = preneoplastic BRCA1+/- tissue; TN-B1= BRCA1-associated TNBCs). E Same t-SNE map as (D) but colored by cluster (cluster resolution 0.15). F Expression  of epithelial  markers indicated on the combined t-SNE plot as in (D, E) for BRCA1  preneoplastic and BRCA1-associated tumor cells. G Epithelial  clusters were identified by EPCAM expression  and  non-epithelial cells  are indicated by the dotted line. H Same t-SNE map as in (D, E) but colored according to cancerous state: preneoplastic tissue (blue) and BRCA1-associated TNBCs (yellow). I Box plots of signature expression  scores for the 13 cell clusters in (D, E) according to human breast epithelial  and stromal  gene signatures. Cluster 1 corresponds to tumor cells, while clusters 6, 9 and 10 represent adjacent normal LP, basal  and ML cells, respectively. Box plots show quartiles, minimum and maximum.",
    "ncbi_link": "BRCA1: 672
EPCAM: 4072"
  },
  {
    "caption": "A Reclustered EPCAM-negative cells (excluding clusters 1, 6, 9 and 10 revealed immune/stromal cells in the microenvironment, identified using lineage markers. B Combined t-SNE plot as in (A) of the single-cell transcriptomes of immune  and stromal cells from preneoplastic tissue of BRCA1  mutation carriers (blue; preneo) and BRCA1-associated TNBCs (yellow; tumor). C t-SNE plots showing expression  profiles of cardinal markers of immune  and stromal cells. D Bar plots showing the percentage of cells expressing typical immune cell (including Treg) genes for clusters in (A) by preneoplastic vs tumor. E Left panel, same t-SNE map as in (A) but separated into cells from preneoplastic (blue) and tumor specimens (yellow). Endothelial cell (endo), fibroblast cell (fibro) and pericytes (peri) clusters are marked. Right panel, proportion of clusters as in (A) according to tissue type. F Relative cluster sizes as in (E) but by individual patient.",
    "ncbi_link": "BRCA1: 672
EPCAM: 4072"
  },
  {
    "caption": "H Heat map of top differentially expressed genes in the major immune/stromal cell  clusters, identified in (A).  BRCA1+/- preneoplastic cells, blue; BRCA1-associated tumor cells, yellow.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "A-C t-SNE plots of combined scRNA-seq  profiles of total cells from 8 TNBC  tumors, 6 HER2+ tumors and 13 ER+ tumors respectively. Integration and cluster sizes for the same cells Cells colored by cluster (top left panels), EPCAM expression  (top right), cancer subtype marker (bottom left) or MKI67 expression  (bottom right). Dotted lines delineate epithelial cells  (top panels) and cycling epithelial cells (bottom panels). Normal epithelial  subsets (normal) are also demarcated by dotted lines in the upper-right panels of B and C. D InferCNV plots to map inferred copy number variation (CNV) for the combined tumor scRNA-seq expression  data for the epithelial  clusters indicated in panels A-C. scRNA-seq data from normal  breast epithelial cells  (N-1105-epi) served as a reference for normalization. Each row represents a gene and each column cells from a cluster in a single tumor. The tumor clusters are color-coded as in A-C. Amplifications (red) and deletions (blue) are inferred from the  gene expression. Tumor cells were distinguished from normal (N) cells by abundance of CNV.",
    "ncbi_link": "EPCAM: 4072
MKI67: 4288"
  },
  {
    "caption": "H Combined t-SNE transcriptome profiles  of two distinct  ER+ tumors isolated from the same breast of a patient: ER-0029-7C (blue) and ER-0029-9C (yellow). The corresponding t-SNE cell clusters are shown in the middle panel and expression  of EPCAM  is shown in the right-hand panel.",
    "ncbi_link": "EPCAM: 4072"
  },
  {
    "caption": "(A) NPM1 expression in CD34+Lin- cells from myelodysplastic syndrome (MDS) patients compared to healthy volunteers (n = 29).",
    "ncbi_link": "NPM1: 4869"
  },
  {
    "caption": "(C) Representative distribution of Tubulin and CDC42 in Ctrl, 4-months old Npm1 cKO and 2-years old WT HSCs determined by IF. Scale bars, 5 μm.",
    "ncbi_link": "Npm1: 18148"
  },
  {
    "caption": "(F ) HSCs of Ctrl, 4-months old Npm1 cKO and 2-years old WT mice were sorted and stained for TOM20. Representative images (top) and quantification of mitochondrial volume and number (bottom) in single cells (n = 58 cells in Ctrl, n = 70 cells in cKO and n = 23 cells in Old, from 3 mice per group), identified by volume rendering of TOM20. Scale bars, 2 μm.",
    "ncbi_link": "Npm1: 18148"
  },
  {
    "caption": "(J) Representative images (top) and quantification of mitochondrial volume and number (bottom), identified by volume rendering of TOM20, in MDS-L cells transfected with siNPM1 or control (siCTRL) (n = 58 cells per group, from 3 transfected MDS-L cultures). Scale bars, 2 μm.",
    "ncbi_link": "NPM1: 4869"
  },
  {
    "caption": "(F) Representative peripheral blood (PB) smears. Insets show the differentiated granulocytes (a, b) in control mice, and anisocytosis (c), dysplastic myeloid cells (d-g) in Npm1 cKO mice (Npm1F/FVav1Cre+). Npm1 cKO mice show dysplastic erythroid cells (polychromatophilic, blue arrowhead; schistocyte, blue-outlined arrowhead; tear drop, Howell-Jolly bodies, black arrowhead; black-outlined arrowhead), dysplastic monocytes (black arrow), and dysplastic neutrophils (d-f). Scale bars, 10 μm.",
    "ncbi_link": "Cre: 2777477
Npm1: 18148
Vav1: 22324"
  },
  {
    "caption": "(C) Npm1 and p53 protein levels in KSL cells of Ctrl (Npm1F/FVav1Cre-), and cKO (Npm1F/FVav1Cre+) mice.",
    "ncbi_link": "Cre: 2777477
Npm1: 18148
Vav1: 22324"
  },
  {
    "caption": "Relative TSC1 and TSC2 mRNA expression levels determined by qRT-PCR for high MYC (-Tet) versus low MYC (+Tet) P493-6 cells treated for 24 h with tetracycline (mean ± st.dev., n=3 technical replicates) *p< 0.05; **p< 0.01; statistical relevance was determined by unpaired t-test (two-tailed).",
    "ncbi_link": "MYC: 4609
TSC1: 7248
TSC2: 7249"
  },
  {
    "caption": "qRT-PCR analysis of TSC1 mRNA levels upon MYC suppression for 24h-72h (+Tet). Immunoblots for 24h and 48h (+Tet) show S6K and phosphorylation (P-) of S6K as downstream mTORC1 target, and β-actin loading control. For 72 h (+Tet) the immunoblots show expression of MYC and phosphorylation (P-) of downstream mTORC1 targets S6K and S6, and α-tubulin as loading control.",
    "ncbi_link": "MYC: 4609
TSC1: 7248"
  },
  {
    "caption": "Upper immunoblot shows the reduction in TSC1 levels upon expression of two different TSC1-specific sh-RNAs compared to scrambled control sh-RNA in P493-6 cells. Other blots show the expression levels of TSC2, S6K/P-S6K, S6/P-S6 and α-tubulin for loading control.",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Left graph shows the multiplication rate of P493-6 (-Tet) cells expressing either a scrambled control sh-RNA or a TSC1-specific sh-RNA determined by viable cell counting 3 days after seeding of equal number of viable cells (determined by Trypan blue exclusion; mean ± st.dev., n=3 biological replicates). Right graph shows percentage of apoptotic P493-6 (-Tet) cells expressing scrambled control shRNA or a TSC1-specific sh-RNA determined by FACS analysis of AnnexinV/7AAD stained cells (mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Rapamycin treatment recovers survival of TSC1 knockdown in P493-6 cells. Relative viable cell number counts of P493-6 (-Tet) cells expressing scrambled control shRNA or TSC1-specific sh-RNA 14 days after seeding equal number of viable cells (Trypan blue exclusion), in the presence of 30pM rapamycin where indicated (mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "TSC1 knockdown is synthetic lethal with MYC deregulation. U2OS-MYC-ER cells expressing either scrambled control sh-RNA or TSC1-specific sh-RNA were treated with hydroxytamoxifen to induce MYC and rapamycin (100 nM) where indicated. Percentage of apoptotic cells was determined with Annexin/7AAD staining 4 days after MYC induction (mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Survival rate of different BL cell lines upon TSC1 knockdown. Graphs show numbers of viable cells expressing either a scrambled control sh-RNA or a TSC1-specific sh-RNA 3 days after seeding of equal number of viable cells (determined by trypan blue exclusion; mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Immunoblots of control- or TSC1-shRNA expressing BL2 or DG75 cells treated with different concentrations of Rapamycin to either completely inhibit mTORC1 activity (10nM) or titrate the activity to control levels (30 pM), and survival rate of these cells over 7 days (mean ± st.dev., n=3 biological replicates); (Bl2 cells were selected for stable knockdown with Puromycin, DG75 cells without selection).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Ramos cells expressing either a TSC1-specific or a control shRNA were inoculated into NOD/SCID mice and tumor volume was measured regularly. The immunoblot shows the level of knockdown of TSC1 (sh-TSC1b) compared to control (sh-contr), and levels of TSC2 and phosphorylated mTORC1 target proteins before inoculation. Tumor growth curves show mean ± SEM (n=8/group). Pictures of xenotransplanted human Ramos lymphoma tumors 35 days after inoculation. The top panels show tumors derived from Ramos cells stably expressing control sh-RNA (sh-contr); the lower panels show tumors derived from Ramos cells stably expressing TSC1-specific sh-RNA (sh-TSC1b).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "TSC1 knockdown increases respiration in an mTORC1 and MYC dependent manner. Rate of basal oxygen consumption in P493-6 (-Tet) cells expressing scrambled control sh-RNA or TSC-specific sh-RNA, treated with 20 nM rapamycin for 12 h, or tetracycline to repress MYC for 48 h where indicated",
    "ncbi_link": "MYC: 4609
TSC: 7248
TSC1: 7248"
  },
  {
    "caption": "TSC1 knockdown increases respiration in an mTORC1 and MYC dependent manner. Rate of basal oxygen consumption in response to 10 μM of the chemical uncoupler DNP to determine maximal respiration or 10 μM of the ATP synthase inhibitor oligomycin where indicated (B) (mean ± st. dev., n=6 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Ratio of mitochondrial to genomic DNA determined by qRT-PCR in P493-6 (-Tet) cells expressing either scrambled control sh-RNA or a TSC1-specific sh-RNA, and treated with 20 nM rapamycin for 12 h where indicated (mean ± st.dev., n=3 technical replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "expression of cytochrome C (CYCS) or ATP5G1 mRNAs (D) determined by qRT-PCR in P493-6 (-Tet) cells expressing either scrambled control sh-RNA or a TSC1-specific sh-RNA, and treated with 20 nM rapamycin for 12 h where indicated (mean ± st.dev., n=3 technical replicates).",
    "ncbi_link": "ATP5G1: 516
CYCS: 54205
cytochrome C: 54205
TSC1: 7248"
  },
  {
    "caption": "TSC1 knockdown results in elevated ROS levels in a MYC and mTORC1 dependent manner. FACS analysis of DCF-DA stained P493-6 (-Tet) cells expressing scrambled control sh-RNA or a TSC1-specific sh-RNA to evaluate ROS production and treated with 20 nM rapamycin for 12 h and tetracycline for 48 h where indicated (mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "TSC1 knockdown results in increased phosphorylation of SAPK/JNK. Immunoblot of SAPK/JNK Thr183/Tyr185-phosphorylation in P493-6 (-Tet) cells expressing scrambled control sh-RNA or a TSC1-specific sh-RNA. α-tubulin expression serves as loading control.",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Antioxidant treatment rescues cells from death caused by TSC1 knockdown. Relative viable cell number counts of P493-6 (-Tet) cells expressing scrambled control shRNA or TSC1-specific sh-RNA 3 days after seeding equal number of viable cells (Trypan blue exclusion), in the presence of 10 μM of the antioxidant BHA where indicated (mean ± st.dev., n=3 biological replicates).",
    "ncbi_link": "TSC1: 7248"
  },
  {
    "caption": "Accumulation of EU-labeled (Click-It, Invitrogen) TSC1-mRNA over 3 h in high MYC (-Tet) versus low MYC (+Tet) P493-6 cells (mean ± st. dev., n=3 technical replicates).",
    "ncbi_link": "MYC: 4609
TSC1: 7248"
  },
  {
    "caption": "Drawing of the TSC1 promoter and luciferase-reporter constructs with the predicted E-box (CACGTG, pos. -317/-322) indicated. Relative luciferase units (RLU) of co-transfection experiments using the indicated TSC1-promoter-reporters with MYC normalized to empty pcDNA3 expression vector in HeLa cells (mean ± st. dev., n=3). Immunoblot shows MYC overexpression and α-tubulin as loading control.",
    "ncbi_link": "MYC: 4609
TSC1: 7248"
  },
  {
    "caption": "TSC1 mRNA turnover determined by pulse and chase (Click-It, Invitrogen) over 8 h in P493-6 cells, either treated with tetracycline to repress MYC or left untreated (mean ± st.dev., n=3 technical replicates).",
    "ncbi_link": "MYC: 4609
TSC1: 7248"
  },
  {
    "caption": "miR-15a expression determined by qRT-PCR in P493-6 cells treated with tetracycline for 3 days (+Tet) to suppress MYC expression or in untreated (-Tet) cells (mean ± st. dev., n=3 technical replicates).",
    "ncbi_link": "miR-15a: 406948
MYC: 4609"
  },
  {
    "caption": "Immunoblots showing expression levels of TSC1, S6K/P-S6K and α-tubulin in P493-6 and HEK293T cells overexpressing miR-15a or a control miRNA. At the right miR-15a overexpression was determined by qRT-PCR in P493-6 and HEK293T cells (mean ± st. dev., n=3 technical replicates).",
    "ncbi_link": "miR-15a: "
  },
  {
    "caption": "Immunoblot showing TSC1 expression, S6K/P-S6K and α‑tubulin in MCF-7 cells transfected with LNA modified anti-sense miR-15a oligos or control LNAs. At the right, successful miR-15a knockdown determined by qRT-PCR in MCF-7 cells is shown (mean ± st. dev., n=3 technical replicates).",
    "ncbi_link": "miR-15a: "
  },
  {
    "caption": "Relative luciferase activities (RLU) derived from reporter constructs containing TSC1-3´UTR wild type sequences or with mutated miR-15a seed sequence binding site on co-transfection with miR-15a in MCF-7 cells (mean ± st. dev., n=3 biological replicates). The drawing at the left shows the TSC1-3'UTR with the position of the miR-15a/16-1 seed sequence and used mutation indicated.",
    "ncbi_link": "miR-15a: 
TSC1: 7248"
  },
  {
    "caption": "Rate of oxygen consumption in P493-6 (-Tet) cells ectopically expressing miR-15a or control-miRNA vector, under basal conditions and in response to 10 μM DNP or 10 μM oligomycin where indicated (mean ± st. dev., n=8 biological replicates).",
    "ncbi_link": "miR-15a: "
  },
  {
    "caption": "Impaired wound closure in αSMA-TK mice. (A) IHC for αSMA+ cells in wound tissue sections at day 6 post-wounding. Representative images are shown. Scale bar, 50 µm. Black boxes denote zoomed regions displayed in bottom panels. (B) Quantification of αSMA+ cells at day 6 post-wounding. WT, N=6; TK, N=5 biological replicates. Two-tailed non-parametric Mann-Whitney test performed.",
    "ncbi_link": "αSMA: 11475
TK: 24271467"
  },
  {
    "caption": "(F) Expression levels of ACTA2 in normal and diabetic human wound tissue. RNA-seq reads are derived from (Davis et al., 2020, Data ref: Davis et al, 2020). Normal, N=3; diabetic, N=4 biological replicates. Data are presented as a box and whisker plot of min to max values. Unpaired t-test performed.",
    "ncbi_link": "ACTA2: 59"
  },
  {
    "caption": "(J-O) Impaired granulation tissue formation and angiogenesis in αSMA-TK mice. (J) Representative H&E images of wound tissue sections at day 17 post-wounding. Granulation areas are marked by black lines, triangles (open: incomplete closure, filled: closed wounds) denote the epithelial tongues. Epi, epidermis; derm, dermis regions denoted. Scale bar: 200 μm. (K) Granulation tissue thickness measured on digital images and normalized to the average values in the WT control (set to 100%). NA (not assessed) reflects the lack of granulation in αSMA-TK mice. WT, N=5; TK, N=4 biological replicates. (L) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (M) Quantification of CD31+ cells per visual field normalized to WT mice. WT, N=3; TK, N=5 biological replicates. (N) IHC for hypoxyprobe (brown) on wound tissue sections at day 17 post-wounding. Black boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (O) Quantification of hypoxyprobe area per visual field normalized to WT mice. WT, N=5; TK, N=6 biological replicates.",
    "ncbi_link": "αSMA: 11475
TK: 24271467"
  },
  {
    "caption": "(D) Representative FACS plots of digested skin from bone marrow (BM) transplanted αSMA-RFP mice 17 days post-wounding. (E) FACS quantification of αSMA-RFP+ cells in wounds of BM transplanted mice. αSMA-RFP with αSMA-RFP BM, N=2; WT with αSMA -RFP BM, N=3; αSMA-RFP with WT BM, N=4 biological replicates. One-way ANOVA with Tukey's multiple comparison test performed comparing WT with αSMA-RFP BM and αSMA-RFP with WT BM to αSMA-RFP with αSMA-RFP BM. (",
    "ncbi_link": "RFP: 
αSMA: 11475"
  },
  {
    "caption": "(L) Representative H&E images of wound tissue sections at day 17 post-wounding. Granulation areas are marked by black lines. Scale bar, 200 μm. (M) Granulation tissue thickness measured on digital images and normalized to the average values in the WT control. WT, N=3; FAP-TK, N=3; WT, N=17, FSP1-TK, N=9 biological replicates. (N) Immunofluorescent staining for CD31 (red) and nuclei on wound tissue sections at day 17 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (O) Quantification of CD31+ cells per visual field normalized to WT mice. WT, N=4; FAP-TK, N=4; WT, N=3; FSP1-TK, N=3 biological replicates. (P) IHC for hypoxyprobe (brown) on wound tissue sections at day 17 post-wounding. Black boxes denote zoomed regions depicted in right panels. Scale bar, 100 μm. (Q) Quantification of hypoxyprobe area per visual field normalized to WT mice. WT, N=3; FAP-TK, N=3; WT, N=3; FSP1-TK, N=4 biological replicates. (R) W",
    "ncbi_link": "FSP1: 71361
FAP: 14089
TK: 24271467"
  },
  {
    "caption": "(C) Enrichment plot of genes in αSMA C1 (left panel). Violin plots for genes enriched in αSMA C1 (right panels). (D) Enrichment plot of genes in αSMA C2 (left panel). Violin plots for genes enriched in αSMA C2 (right panels). (E) Enrichment plot of genes in αSMA C3 (left panel). Violin plots of enriched genes in the αSMA C3 cluster (right panels). Raw scRNA-seq data are derived from (Haensel et al., 2020, Data ref: Haensel et al 2020). Da",
    "ncbi_link": "αSMA: 11475"
  },
  {
    "caption": "(A) IHC for collagen I on wound tissue sections at day 17 post-wounding (brown stain). Black boxes denote zoomed regions depicted in bottom panels. Scale bar: 50 μm. (B) Quantification of collagen I positive area normalized to the average area in WT controls. WT, N=5; TK, N=5 biological replicates. (C) Polarized light images of picrosirius red stained wound tissues at day 17 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in bottom panels. Scale bar, 50 µm. (D) Quantification of collagen fiber (picrosirius red) percent area normalized to the average area in WT controls. WT, N=3; TK, N=3 biological replicates. (E-",
    "ncbi_link": "TK: 24271467"
  },
  {
    "caption": "(E-H) Reduced collagen deposition in Col1α1cKO wounds. (E) IHC for collagen I on wound tissue sections at day 14 post-wounding (brown stain). Black boxes denote zoomed regions depicted in bottom panels. Scale bar: 25 μm. (F) Quantification of collagen I positive area normalized to the average area in WT controls. WT, N=7; Col1α1cKO, N=4 biological replicates. (G) Polarized light images of picrosirius red stained wound tissues at day 14 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in bottom panels. Scale bar, 50 µm. (H) Quantification of collagen fiber percent area and fiber width normalized to the average area and width, respectively, in WT controls. WT, N=4; Col1α1cKO, N=5 biological replicates.",
    "ncbi_link": "Col1α1: 12842"
  },
  {
    "caption": "(J-M) Reepithelization and vascularization in WT and Col1α1cKO mice. (J) Representative images of keratin 5 (Krt5, red) stained wounds at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 500 µm. (K) Quantification of epidermal thickness. WT, N=6; Col1α1cKO, N=5 biological replicates. (L) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 20 μm. (M) Quantification of CD31+ area per visual field normalized to WT mice. WT, N=6; Col1α1cKO, N=5 biological replicates.",
    "ncbi_link": "Col1α1: 12842"
  },
  {
    "caption": "(F-K) Reepithelization, granulation tissue formation, and vascularization in WT and Itgb1cKO mice. (F) Representative images of keratin 5 (Krt5, red) stained wounds at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 500 µm. (G) Quantification of epidermal thickness. WT, N=4; Itgb1cKO, N=6 biological replicates. (H) Immunofluorescent staining for CD31 (red) and nuclei (blue) on wound tissue sections at day 14 post-wounding. White boxes denote zoomed regions depicted in right panels. Scale bar, 20 μm. (I) Quantification of CD31+ area per visual field normalized to WT mice. WT, N=6; Itgb1cKO, N=6 biological replicates. (J) Polarized light images of picrosirius red stained wound tissues at day 14 post-wounding. Red: collagen fibers. White boxes denote zoomed regions depicted in right panels. Scale bar, 50 µm. (K) Quantification of collagen fiber percent area normalized to the average area in WT controls. WT, N=6; Itgb1cKO, N=6 biological replicates. (L) Quantification of collagen fiber width normalized to the average width in WT controls. WT, N=6; Itgb1cKO, N=6 biological replicates. D",
    "ncbi_link": "Itgb1: 16412"
  },
  {
    "caption": "(D) Growth rate  in rich medium (LB) under different levels of overexpression of a gratuitous  protein from a T5-lac   promoter; overexpression burden is controlled by IPTG  concentration Data information: Error bars in D, show standard deviation from 6, 12, and 18 biological replicates, respectively; day-to-day reproducibility of growth rate  measurements is high",
    "ncbi_link": "lac: "
  },
  {
    "caption": "(B) Growth rate as a function of TMP  concentration for different paths through IPTG-TMP  concentration space Constant FolA   is shown in black and inverted FolA   regulation in red. Wild-type  dose-response curve  (blue line; is shown for comparison. (C) Steepness of the  dose response curve  (quantified as dose-sensitivity n) for the three cases in B. Inset: Normalized FolA expression  level as a function of TMP  concentration for the three cases in B; WT (blue) colors as in the bar chart and in B. Data information: Error bars in B show standard deviation of the measured growth rates  used for interpolating the values shown; the entire experiment was replicated once Error bars in C show standard deviation of parameter estimates from Hill function fit.",
    "ncbi_link": "FolA: 944790"
  },
  {
    "caption": "(D) Quantification of EGFP-LC3 puncta in MCF7-EGFP-LC3 cells 56 h after transfection with the indicated siRNAs. When indicated, cells were exposed to 100 nM rapamycin for the last 3 h. RPTOR (raptor) and BECN1 (beclin1) siRNAs served as positive and negative controls, respectively.",
    "ncbi_link": "BECN1: 8678
RPTOR: 57521"
  },
  {
    "caption": "(E) Autophagic flux was measured as the ratio between luciferase activities in MCF7-RLuc-LC3WT and MCF7-RLuc-LC3G120A cells transfected with the indicated siRNAs 56 h earlier and left untreated or treated with 100 nM rapamycin for the last 3 h. Error bars are SDs for a representative (n = 5) triplicate experiment with a minimum of 4 × 10 randomly chosen areas/sample analyzed (D) or three independent experiments (F). *, P < 0.05; **, P < 0.01; ***, P < 0.001, as compared with similarly treated control siRNA-transfected samples.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) Representative immunoblots of the indicated proteins from whole-cell lysates of MCF7-EGFP-LC3 cells stably infected with control or CIP2Ar (siRNA-resistant CIP2A)-encoding lentivirus, transfected with the indicated siRNAs for 53 h, and treated with 100 nM rapamycin (Rapa) for 0-20 min.",
    "ncbi_link": "CIP2A: 57650
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) MCF7-EGFP-LC3 cells stably infected with control or CIP2Ar-encoding lentivirus were transfected with indicated siRNAs for 48 h and analyzed for EGFP-LC3 puncta formation.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(D) MCF7-EGFP-LC3 cells transfected with control (−) and CIP2A siRNAs together with an empty vector (−) or MYC-S62A cDNA as indicated were analyzed 56 h later for EGFP-LC3 puncta (left) and expression of indicated proteins (right).",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(E) Representative immunoblots (left) of indicated proteins from whole-cell lysates of MCF7 cells treated with the control (C), RPTOR (RP), or CIP2A (CIP) siRNAs for 56 h and densitometric quantification of three independent experiments (right). Error bars show SDs for three independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001, compared with Student's t test as indicated (C and D) or with control siRNA-transfected samples (E). Black lines indicate that intervening lanes have been spliced out.",
    "ncbi_link": "CIP2A: 57650
RPTOR: 57521"
  },
  {
    "caption": "(A, top left) Quantification of EGFP-LC3 puncta in MCF7-EGFP-LC3 cells infected with control or CIP2A lentiviral shRNAs. Representative immunofluorescence images (right) and immunoblots (bottom) are shown. (B) Mean cell diameters of MCF7-EGFP-LC3 cells infected as in A were measured with a cytometer (NucleoCounter NC-3000; Chemometec AS) equipped with Via1-Cassettes (Chemometec AS).",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(E) Light microscopy pictures of MCF10A cells at passage 8 after infection with control or CIP2A-encoding lentivirus.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(A and B) In vitro translated full-length CIP2A was incubated with purified human PP2A complex and HA-Raptor (A) or HA-S6K1 (B) purified from transiently transfected MCF7 cells. Protein complexes were immunoprecipitated with anti-HA antibody and analyzed by immunoblotting as indicated. Nonspecific IgG served as a control. Note that human reticulocyte (RC) lysate used for in vitro translation of CIP2A contained detectable amounts of PP2Ac.",
    "ncbi_link": "CIP2A: 57650
S6K1: 6198
Raptor: 57521"
  },
  {
    "caption": "(D) Endogenous raptor protein complexes immunoprecipitated from MCF7 cells stably infected with control (Ctr) or CIP2A shRNA lentiviruses (Fig. 3 A) and starved for amino acids for 20 min when indicated were analyzed by immunoblotting and PP2A activity assay. Immunoblots of corresponding cell lysates are shown on the right.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(E) Raptor protein complexes immunoprecipitated from MCF7 cells treated with control (C) or PPP2R1A (R1A) siRNAs for 56 h were analyzed by immunoblotting with the indicated antibodies. Immunoblots of corresponding cell lysates are shown on the left.",
    "ncbi_link": "PPP2R1A: 5518"
  },
  {
    "caption": "(F) HA-S6K1 protein complexes immunoprecipitated from MCF7 cells stably infected with control or CIP2A shRNA lentiviruses (Fig. 3 A), transiently transfected with HA-RPS6K1 cDNA and starved for amino acids for 20 min when indicated, were analyzed by immunoblotting. Immunoblots of corresponding cell lysates are shown on the right.",
    "ncbi_link": "CIP2A: 57650
RPS6K1: 6198"
  },
  {
    "caption": "(G) Enzymatic activity of a purified PP2A holoenzyme incubated with human reticulocyte lysate with or without in vitro translated full-length CIP2A. Error bars are SDs for four (D) independent experiments or a representative triplicate experiment (C and G).",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(B) qPCR analysis of CIP2A and MYC mRNA levels in MCF7 cells treated as in A. AA-starv, amino acid starvation; a.u., arbitrary unit. Error bars show SDs for three independent experiments.",
    "ncbi_link": "CIP2A: 57650
MYC: 4609"
  },
  {
    "caption": "(C) Representative immunoblots of the indicated proteins from whole-cell lysates of MCF7 cells treated with ULK1 or SQSTM1 siRNAs for 54 h before the exposure to fresh medium (0) or amino acid starvation (−AA) for 12 h. Ctr, control.",
    "ncbi_link": "SQSTM1: 8878
ULK1: 8408"
  },
  {
    "caption": "(F) Representative immunoblots of an endogenous CIP2A protein complex immunoprecipitated from lysates of MCF7 cells left untreated or treated for 4 h with 100 nM rapamycin (Rapa) and 2 nM ConA as indicated. Mouse IgG served as a negative control.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(G) MCF7 cells were treated with 100 nM rapamycin, 2 nM ConA, and 2 µM MG132 for 24 h as indicated. Endogenous CIP2A was immunoprecipitated (IP) in stringent conditions (no coimmunoprecipitation of p62) and analyzed by immunoblotting using antibodies against CIP2A, monoubiquitin, and polyubiquitin. Short (<100 kD), medium (>150 kD), and long (100-130 kD) exposures are shown.",
    "ncbi_link": "CIP2A: 57650"
  },
  {
    "caption": "(J) Lysates from MCF7 cells transfected with the CIP2A-FLAG construct (Junttila et al., 2007) and the indicated ubiquitin-HA constructs were subjected to anti-FLAG immunopurification in denaturing conditions with 0.1% SDS followed by immunoblotting with the indicated antibodies. Black lines indicate that intervening lanes have been spliced out. Ub, ubiquitin; WT, wild type.",
    "ncbi_link": "ubiquitin: 6232///7314///7311///7316"
  },
  {
    "caption": "(B) Fraction of unlabeled nucleosides, nucleic bases and PPP intermediates as a function of starvation time, in wild‐type and autophagy deficient (atg7 deletion) yeast. The x axis represents minutes after carbon starvation, and the y axis represents fraction of unlabeled metabolites (mean±range of N=2 biological replicates).",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(C) Ratio of metabolite levels in atg7 strain versus wild‐type strain in carbon starvation.",
    "ncbi_link": "atg7: 856576"
  },
  {
    "caption": "(D) Ratio of metabolite levels in bcy1 strain and snf1 strain versus wild‐type strain in carbon starvation.",
    "ncbi_link": "bcy1: 854778
snf1: 852088"
  },
  {
    "caption": "(A) Ratio of metabolite levels in sdt1 and phm8 strains versus wild‐type strain in carbon starvation. All reported values are log2 transformed ratios; data are mean of duplicate samples at each time point.",
    "ncbi_link": "phm8: 856759
sdt1: 852648"
  },
  {
    "caption": "(B) Summary of transcripts data of PHM8, SDT1 and other enzymes in the pathway (Gasch et al, 2000; Bradley et al, 2009; Klosinska et al, 2011). All values are log2 transformed fold changes.",
    "ncbi_link": "PHM8: 856759
SDT1: 852648"
  },
  {
    "caption": "(C) Screening of Phm8's phosphatase activity against 90 phosphorylated compounds. Phosphatase activity was measured in the presence of 0.5 mM substrate and 5 mM Mg2+ (pH=7.0, 30°C). Compounds with specific activity higher than 0.1 μmol/mg/min are shown. The x axis represents specific phosphatase activity (μmol of phosphate produced per minute per mg of enzyme, mean±range of N=2 replicates).",
    "ncbi_link": "Phm8: 856759"
  },
  {
    "caption": "(D) Top table: absolute intracellular concentration of nucleotide monophosphates in carbon starvation. Bottom plots: Phosphatase activity of Phm8 and Sdt1 as a function of CMP concentration. The x axis represents CMP concentration and the y axis represents specific phosphatase activity (μmol of phosphate produced per minute per mg of enzyme, mean±range of N=2 replicates).",
    "ncbi_link": "Phm8: 856759
Sdt1: 852648"
  },
  {
    "caption": "Confirmation that Pnp1 is the physiological purine nucleoside phosphorylase, Urh1 is the pyrimidine hydrolase, and Prm15 (Pgm3) is the phosphoribomutase. Ratio of metabolite levels in pnp1/urh1, pnp1, urh1 and prm15 (pgm3) strains versus wild‐type strain during carbon starvation. Data are shown in heat map format, with each line reflecting the dynamics of the ratio of the metabolite levels in a particular strain versus wild‐type strain. All reported values are log2 transformed ratios; data are mean of duplicate samples at each time point.",
    "ncbi_link": "pnp1: 850906
pgm3: 855321
prm15: 855321
urh1: 852009"
  },
  {
    "caption": "(B‐E) DHAP, SBP and S7P levels in wild type, tkl1/tkl2 (B), tal1/nqm1 (C) and pfk1 (E) strains upon carbon starvation, and wild‐type strain upon abruptly switching from glucose to no carbon (WT) versus to dihydroxyacetone (WT+DHA) as the sole carbon source (D). The x axis represents hours after carbon starvation, and the logarithmic y axis represents absolute intracellular concentration (mean±range of N=2 biological replicates).",
    "ncbi_link": "nqm1: 852934
pfk1: 853155
tal1: 851068
tkl1: 856188
tkl2: 852414"
  },
  {
    "caption": "(A) Level of hallmark metabolites and energy charge in wild type, phm8 and pnp1/urh1 strains in starvation. The x axis represents hours after starvation, and the logarithmic y axis represents energy charge ([ATP]+0.5[ADP]/([ATP]+[ADP]+[AMP]) or absolute intracellular concentration (mean±range of N=2 biological replicates).",
    "ncbi_link": "phm8: 856759
pnp1: 850906
urh1: 852009"
  },
  {
    "caption": "(B and C) Growth and viability of wild type, phm8 and pnp1/urh1 strains in starvation.",
    "ncbi_link": "phm8: 856759
pnp1: 850906
urh1: 852009"
  },
  {
    "caption": "(D) Growth of wild type, phm8 and pnp1/urh1 strains in the switch from glucose to glycerol+ethanol. The x axis represents hours after starvation and the logarithmic y axis represents optical density (A600) in (B and D) and percentage of live cells calculated by dividing the number of colonies formed after starvation by the number of colonies formed before starvation in (C) (mean±range of N=2 biological replicates).",
    "ncbi_link": "phm8: 856759
pnp1: 850906
urh1: 852009"
  },
  {
    "caption": "(C and D) DHAP, S7P, G6P, and glutathione levels and NADPH/NADP+ ratio in wild type, phm8 and pnp1/urh1 strains in the experiment shown in (A) The x axis represents minutes after oxidative stress, and the y axis represents absolute intracellular concentration or ratio of intracellular concentration (mean±range of N=2 biological replicates).",
    "ncbi_link": "phm8: 856759
pnp1: 850906
urh1: 852009"
  },
  {
    "caption": "(E) Viability of wild type, phm8 and pnp1/urh1 strains in oxidative stress. The y axis represents percentage of survived cells calculated by dividing the number of colonies formed after oxidative stress by the number of colonies formed under the same starvation condition but without H2O2 treatment (mean±range of N=2 biological replicates).",
    "ncbi_link": "phm8: 856759
pnp1: 850906
urh1: 852009"
  },
  {
    "caption": "Two-class comparison of genetic dependencies from a publically available genome-scale CRISPR-Cas9 screen of HNSCC (12 cell line) versus SQCLC (10 cell lines) identified a subset of differentially expressed proteins that were also differential dependencies in these tumor types. The x-axis represents the effect size of the mean difference of dependency scores in HNSCC compared to SQCLC cell lines. Positive effect size indicates a greater mean dependency in HNSCC; negative effect size indicates a greater mean dependency in SQCLC. The y-axis represents the statistical significance of differential enrichment calculated as -log10(p-value) from a two-sided t-test. The p-values used for this plot are uncorrected for multiple hypothesis testing. Highlighted in green are genetic dependencies that were also identified as differentially expressed proteins in our study.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "Using CRISPR/Cas9, MyD88 knock-out (KO) and AAVS1KO (control) pDCs  were generated. MyD88 protein levels in KO and control pDCs were analyzed by western blotting",
    "ncbi_link": "CRISPR: 
AAVS1: 17
Cas9: 69900935
MyD88: 4615"
  },
  {
    "caption": "C-D: MyD88KO and control pDCs were either mock treated (mock) or exposed to  SARS-CoV-2  (SARS-2, 1 MOI), supernatants were collected at indicated time points  and analyzed for type I IFNα (C) and CXCL10 (D). Done with n=4 Data information: Bars represent mean values and equal symbols represent equal donors. Statistical significance was determined using Mann-Whitney one-tailed T test in (C) as MyD88-KO data had no variance and values of 0. For (D) a Mann-Whitney two-tailed T test was used for comparison between conditions of mock and MyD88 KO donors.",
    "ncbi_link": "MyD88: 4615"
  },
  {
    "caption": "E-F: Type I  IFNα production was then determined in cell culture supernatant from SARS-CoV-2  exposed TRIFKO or TRIG+MyD88KO (E) and RIG-IKO or RIG-I+MyD88KO (F)  pDCs. Done with n=2",
    "ncbi_link": "RIG-I: 23586
MyD88: 4615
TRIF: 148022
TRIG: 148022"
  },
  {
    "caption": "(C) TNFemARE/ARE mice  show significantly elevated serum  levels of TNF  (wild-type n=5, TNFemARE/+ n=5, TNFemARE/ARE n=5). Data information: data are represented as Mean +/- SEM, n=biological replicates. one-way ANOVA test was used with Tukey's multiple comparisons test, ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(D) Histologic  H&E sections of ileum  and hind paw indicate severe ileitis  and arthritis  in 20-30 w/o SPF TNFemARE/ARE mice  (Scale bars upper panel: 100 μm, scale bars lower panel: 500 μm).",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(H) Ileal flow cytometry  data of 25 w/o TNFemARE mice  show a highly activated innate immune system (n=5/genotype). Data information: data are represented as Mean +/- SEM, n=biological replicates. one-way ANOVA test was used with Tukey's multiple comparisons test, ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(D) Quantitative real-time PCR  reveals increased expression of the tnf  gene in the ileum  in homozygous SPF  and GF mice  (SPF  wild-type n=10, SPF TNFemARE/+ n=10, SPF TNFemARE/ARE n=13; GF  wild-type n=3, GF TNFemARE/+ n=4, GF TNFemARE/ARE n=4). Data information: data are represented as Mean +/- SEM, n=biological replicates, two-way ANOVA test used with Tukey's multiple comparisons test, ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "ncbi_link": "tnf: 21926
TNF: 21926"
  },
  {
    "caption": "(F) Comparing SPF  versus GF  H&E sections of the ileum  shows complete rescue of gut inflammation  under axenic conditions in 20-30 w/o TNFemARE/ARE mice  (Scale bars: 100 μm).",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(C) 20-30 w/o SPF TNFemARE/ARE mice  clearly suffer from inflammation  in the synovio-entheseal complex, which is not rescued in age-matched GF mice. (Scale bars: 200 μm)",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(F) <em>μ</em>CT images of tails  of wild-type versus SPF  and GF TNFemARE/ARE mouse  display fusion of  sacral vertebrae in homozygous SPF  and GF mice, as indicated by yellow arrows.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(B) Gait analysis  of TNFemARE mice  reveals distinct moving patterns of SPF  and GF TNFemARE/ARE mice. Homozygous mice  tend to have smaller footprints, place their feet  with lower mean intensity and generally have a smaller stride length. (SPF  wild-type n=12, SPF TNFemARE/+ n=12, SPF TNFemARE/ARE n=12; GF  wild-type n=8, GF TNFemARE/+ n=20, GF TNFemARE/ARE n=12) Data information: For panel (B), boxplots represent the 25- and 75- percentile with median values as central band, whiskers span min to max value range, n=biological replicates with every datapoint representing 1 paw, two-way ANOVA test used with Tukey's multiple comparisons test, ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(C) H&E sections of the  calcaneo-cuboid joint of 5-15 w/o A20myel-KO mice  indicate immune cell  infiltrates in the synovium  and the fat pad and severe bone marrow edema. (Scale bars: 100 μm)",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(E) Histologic  images of  hind paws of old (44 w/o) GF wild-type (left) versus A20myel-KO (right) mice. The morphology  of the paw  is completely lost in the transgenic mouse  due to severe inflammation. (Scale bars: 200 μm)",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(F) Splenomegaly  in GF A20myel-KO mice  of 15 w/o indicates  systemic inflammation in this mouse  model (wild-type n=7, A20myel-KO n=8). Data information: For panels F), data are represented as Mean +/- SEM, n=biological replicates. For graph (F), two-tailed unpaired t-test was used. ns= p-value > 0.05, * = p-value ≤ 0.05, ** = p-value ≤ 0.01, *** = p-value ≤ 0.001, **** = p-value ≤ 0.0001.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "B, In-vivo ubiquitylation  analyses of LIN28B  in HEK293T  cells in which OTUD6B  was silenced by siRNA. Cells were transfected with the indicated siRNAs and overexpression constructs, then treated with MG132  for 3 hrs. Lysis and IP  was done under denaturing conditions followed by WB  analysis. Data information: For B, exemplary blot  of two independent experiments.",
    "ncbi_link": "OTUD6B: 51633"
  },
  {
    "caption": "C, In-vivo ubiquitylation  assay of LIN28B  in OTUD6B   and a catalytically inactive variant of OTUD6B  (OTUD6B-C158A) overexpressing cells. HEK293T  cells were transfected with indicated combinations of FLAG-LIN28B, HA-Ubiquitin, OTUD6B, OTUD6B-C158A and EV control and treated with MG132  for 3 hrs 24 hrs later. Denatured WCE were subjected to FLAG-IP. WCE and IP  were analyzed by immunoblotting  including a K48-specific ubiquitin  antibody. Exemplary blots  from three independent experiments are shown.",
    "ncbi_link": "FLAG: 
HA: 
LIN28B: 389421
OTUD6B: 51633
Ubiquitin: 7316"
  },
  {
    "caption": "E, Immunoblot  analysis of an in-vitro deubiquitylation assay  using GST-purified OTUD6B  from bacteria and FLAG-purified ubiquitylated LIN28B  from HEK293T. FLAG-IP  was performed under denaturing conditions from HEK293T  WCEs expressing FLAG-LIN28B  and HA-Ubiquitin. Purified FLAG-LIN28B  was eluted from the beads and incubated with GST  or GST-OTUD6B  proteins followed by immunoblot  analysis. Data information: For E: exemplary blot  of two independent experiments.",
    "ncbi_link": "FLAG: 
HA: 
LIN28B: 389421
Ubiquitin: 7316"
  },
  {
    "caption": "A, Co-IP of FLAG-OTUD6B  with endogenous LIN28B  from  MM1.S  cells synchronized in G1/S  and 12 hrs post release.  MM1.S cells stably expressing FLAG-OTUD6B  or FLAG-EV were synchronized at G1/S  and harvested at the indicated  time points after release. IPs  were preformed and analyzed together with WCE by immunoblotting. Data information: All blots  are representations of three independent experiments.",
    "ncbi_link": "FLAG: 
OTUD6B: 51633"
  },
  {
    "caption": "D, Immunoblot  analysis of LIN28B  protein  half-life in  G1/S-synchronized (upper panel) and asynchronous (lower panel) A549  cells upon OTUD6B  depletion. Cells transfected with the respective siRNAs were synchronized  in G1/S-phase or not and treated with cycloheximide  (CHX) as indicated. Data information: All blots  are representations of three independent experiments.",
    "ncbi_link": "OTUD6B: 51633"
  },
  {
    "caption": "A, Correlation between MYC   and OTUD6B  expression in MM patient  samples at diagnosis. mRNA expression in primary CD138+ MM  cells was quantified by  real-time qPCR  (n = 89 patients). Data are fit by linear regression (black line); Pearson r, Pearson correlation coefficient; P < 0.0001; by linear regression and Pearson correlation.",
    "ncbi_link": "MYC: 4609
OTUD6B: 51633"
  },
  {
    "caption": "Male C57BL/6 Nr4a2  cKO or wildtype littermate C57BL/6 mice  were immunised twice with NP-KLH   emulsified in alum. After 2 weeks, 7 μm spleen  sections were stained  with Red:Alexa-Fluor-594-CD4  and Green: FITC-B220   (D) or FITC-GL7    (E). Scale bar represent 100 nm.",
    "ncbi_link": "Nr4a2: 18227"
  },
  {
    "caption": "Male C57BL/6 Nr4a2  cKO or wildtype littermate C57BL/6 mice  were immunised twice with NP-KLH emulsified in alum. Serum  was assessed for level of IgG  antibodies binding NP-31 and NP-4 (F).",
    "ncbi_link": "Nr4a2: 18227"
  },
  {
    "caption": "(B) BAX/BAK-deficient HeLa cells reconstituted with BAX and where indicated HA-Parkin were treated with antimycin A and oligomycin (AO) for 2 h and then 1 µM of each of the BH3 mimetics ABT-737 and S63485 for 6 h. Cell death was assessed at the indicated times by LDH assay. Data is mean +/- SD of four independent experiments.",
    "ncbi_link": "HA: 
BAK: 578
BAX: 581
Parkin: 5071"
  },
  {
    "caption": "(C) BAX/BAK-deficient HeLa cells ectopically expressing BAX and Parkin were treated with antimycin A and oligomycin (AO, 3 h), MG132 (20 µM, 3.5 h) and BH3 mimetics (1 µM of each of ABT-737 and S63485, 1 h). Cytosol and membrane fractions were immunoblotted as indicated. Graph shows densitometric analysis of non-ubiquitinated membrane proteins (top, relative to untreated control) or cytochrome c release (bottom; cytosol/cytosol+membrane, relative to untreated controls) from three independent experiments. Error bars represent mean +/- SD.",
    "ncbi_link": "BAK: 578
BAX: 581
Parkin: 5071"
  },
  {
    "caption": "(D) BAX/BAK-deficient HeLa cells ectopically expressing BAX were treated and analysed",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "(E) UBA pull-down of ubiquitinated proteins following antimycin A and oligomycin (AO) treatment of BAX/BAK-deficient HeLa cells ectopically expressing HA-Parkin and BAX for 3 h. Representative immunoblot from two independent experiments.",
    "ncbi_link": "HA: 
BAK: 578
BAX: 581
Parkin: 5071"
  },
  {
    "caption": "(A) Subcellular fractionation of cytosol and membrane fractions of HeLa cells expressing HA-Parkin following 2 h of antimycin A and oligomycin (AO) treatment.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(E) Whole cell lysates of HA-Parkin and BAK variant-expressing HeLa cells following 3 h antimycin A and oligomycin (AO) treatment with 30 min pre-treatment with MG132 (20 µM), representative immunoblots from three independent experiments.",
    "ncbi_link": "HA: 
BAK: 578
Parkin: 5071"
  },
  {
    "caption": "(A) HeLaParkin cells were treated with CCCP (10 μM), antimycin A and oligomycin (AO) for 2h or GTPP (10 μM) for 6h. Immunoblots are representative of three independent experiments. Graph shows densitometric analysis of non-ubiquitinated proteins relative to untreated control from three independent experiments. Error bars represent mean +/-",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(B) SH-SY5Y neuroblastoma cells expressing Cas9 together with a sgRNA targeting PRKN (sgPRKN) or a non-targeting control (sgCon) were assessed for Parkin expression by immunoblotting of cytosolic fractions.",
    "ncbi_link": "Cas9: 
PRKN: 5071"
  },
  {
    "caption": "SH-SY5Y cells generated in (B) were treated with antimycin A and oligomycin (AO) for 3 h prior to cell lysis and immunoblotting. Mono and di-ubiquitinated BAK in Parkin-expressing cells following AO are indicated (asterisk). Data is representative of three independent experiments.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(D) Domain architecture of human Parkin with positions of selected PD-associated mutations. Ubl, ubiquitin-like; IBR, in-between-RING HeLa cells expressing wild-type Parkin or the indicated PD-associated Parkin mutants were treated with antimycin A and oligomycin (AO) for 2h. Immunoblots are representative of three independent experiments. Graph shows densitometric analysis of non-ubiquitinated proteins in AO-treated samples relative to untreated control from three independent experiments. Error bars represent mean +/- SD. All Parkin constructs were N-terminally FLAG-tagged except R104W.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(A) BN-PAGE and SDS-PAGE of HeLa+HA-Parkin cells treated with 1 µM of each of ABT-737 and S63485 for 3 h (BH3), antimycin A and oligomycin (AO) for 2 h or a combination of the two. Experiment was performed in the presence of 10 µM QVD.oph and immunoblots are representative of three independent experiments.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(B) UBA enrichment of ubiquitinated proteins from HeLa+HA-Parkin cells, BAX-/- BAK-/- (DKO) HeLa cells or wild-type (WT) HeLa cells expressing HA-Parkin in response to 1 µM of each of ABT-737 and S63485 for 3 h (BH3) in the presence of QVD.oph (10 μM). Representative of three independent experiments.",
    "ncbi_link": "HA: 
BAK: 578
BAX: 581
Parkin: 5071"
  },
  {
    "caption": "(C) HeLa cells expressing HA-Parkin and Cas9 were transduced with sgRNA targeting PINK1 or a non-targeting sgRNA control, treated with AO (2 h) to stabilise PINK1 expression and immunoblotted for PINK1.",
    "ncbi_link": "Cas9: 
HA: 
PINK1: 65018
Parkin: 5071"
  },
  {
    "caption": "(D) Parkin activity induced by apoptotic mitochondrial damage is PINK1-dependent. UBA enrichment of ubiquitinated proteins from HeLa cells generated in response to 1 µM of each of ABT-737 and S63485 for 3 h (BH3) in the presence of Q-VD.oph (10 μM). *, ubiquitinated protein. Representative of two independent experiments.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(A) Immunoblot of whole cell lysates of MEFs stably expressing ΔCys variants of BAK.",
    "ncbi_link": "BAK: 12018"
  },
  {
    "caption": "(C) Parkin-mediated ubiquitination limits BAK activation. HeLa+HA-Parkin cells were treated with antimycin A and oligomycin (AO) for 2 h prior to induction of apoptosis with 1 µM of each of the BH3 mimetics ABT-737 and S63485 (BH3 mim) for 1 h. Intracellular flow cytometry was performed using the conformation-specific anti-BAK antibody G317-2. Representative histograms are shown and the fold increase in mean fluorescence intensity (MFI) is plotted from three independent experiments with error bars showing SD. Data are normalised to untreated control.",
    "ncbi_link": "HA: 
Parkin: 5071"
  },
  {
    "caption": "(D) Parkin-mediated ubiquitination limits BAK apoptotic activity. BAK-/-BAX-/- HeLa cells expressing Parkin and BAK were treated with AO (2 h) prior to isolation of mitochondria and treatment with recombinant cBID and analysis of cytochrome c release. Immunoblots are representative of three independent experiments. Graph shows densitometric analysis of three independent experiments or cytochrome c in the supernatant fraction. Error bars represent mean +/- SD.",
    "ncbi_link": "BAK: 578
BAX: 581
Parkin: 5071"
  },
  {
    "caption": "(E) Parkin activity limits cytochrome c release. HeLa cells or HeLa cells expressing Parkin were treated and analysed Immunoblots are representative of three independent experiments. Ubiquitinated BAK indicated (arrow). Graph shows densitometric analysis of three independent experiments showing cytochrome c release (supernatant/supernatant+membrane) relative to 100 nM cBID as 100% release. Error bars represent mean +/- SD.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(F) 5-day-old Col-0Cas9 WT and CRISPR glv seedlings were treated with 100 nM flg22  or co-treated with 1 μM GLV2  for 7 days before measuring fresh weight. Shown is the mean of relative fresh  weight  compared to the MS medium control -/+ SD, n=30-32 biological replicates from 2 pooled experiments (one-way ANOVA, Tukey post-hoc test, a-b p<0.001).",
    "ncbi_link": "CRISPR: 
glv: 831428///6240491///814909///820386///6241076///822736///814929
Cas9: 69900935"
  },
  {
    "caption": "(G) Ethylene production was measured in Col-0Cas9 WT and CRISPR glv  3.5 h after elicitation with 500 nM  flg22  or co-treatment with 1 µM GLV2. Ethylene production was normalized to the average of WT responses to flg22  set as 1. Shown is the mean of n=11-12 biological replicates from 3 pooled experiments -/+ SD (one-way ANOVA, Tukey post-hoc test, a-b p<0.01).",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
glv: 814929///822736///6241076///820386///814909///6240491///831428"
  },
  {
    "caption": "(H) Mean cfu of  Pto DC3000 COR- 4 days after spray inoculation of Col-0Cas9 WT and CRISPR glv; n=12 biological replicates from 3 pooled experiments-/+ SD (Students T-Test, *p<0.05).",
    "ncbi_link": "CRISPR: 
glv: 831428///6240491///814909///820386///6241076///822736///814929
Cas9: 69900935"
  },
  {
    "caption": "(D) PR1 expression  was measured in 10-day-old WT  seedlings treated for 24 h with 100 nM flg22, 1 μM GLV2  or co-treatment. Expression  was normalized to the UBQ house-keeping gene. Shown is the mean of n=4. Symbol colors represent different biological replicates",
    "ncbi_link": "UBQ: 830705
PR1: 815949"
  },
  {
    "caption": "(E)  Ethylene  production was measured in WT and rgi5x and  rgi5x pRGI3::RGI3  #2 and #3 3.5 h after elicitation with 500 nM flg22. Ethylene  production was normalized to the average of WT responses to  flg22  set as 1. Shown is the mean of n=8 biological replicates from 2 pooled experiments -/+ SD (one-way ANOVA, Dunnett post-hoc test, a-b p<0.05).",
    "ncbi_link": "rgi5: 840310
RGI3: 828760"
  },
  {
    "caption": "(C) 5-day-old seedlings of WT, rgi5x and rgi5x pRGI3::RGI3 #2 and #3 were treated with 10 nM  flg22 or co-treated with 1 μM GLV2 for 7 days before measuring fresh weight. Shown is the mean of relative  fresh weight compared to the  MS  medium control -/+ SD, n=32 biological replicates pooled from 4 experiments (Students T-test, **p<0.01).",
    "ncbi_link": "rgi5: 840310
RGI3: 828760"
  },
  {
    "caption": "(B) Quantitative real-time PCR   of FLS2 transcripts from 12-day-old seedlings treated with mock or 1 μM GLV2 for the indicated  time, n=3 biological replicates.  UBQ was used as a house keeping gene. Students T-test revealed no statistical difference for each of the different  timepoints. Data information: Similar results were obtained in 3 independent experiments.",
    "ncbi_link": "UBQ: 830705
FLS2: 834676"
  },
  {
    "caption": "B Yeast two-hybrid analysis for interaction between the above-shown Rabaptin5 segments (Rbpt5#, fused to LexA on the bait plasmid) and residues 257-444 of FIP200 (FIP, fused to the Gal4 activation domain on the prey plasmid) to drive HIS3 expression. Three different clones each were replica-plated on medium with His or without His, but containing 3-amino-1,2,4-triazole (3AT; an inhibitor of His synthesis to increase stringency) and grown in the absence of Trp and leucine as a control. As negative controls, empty bait or prey plasmids were used. The asterisk indicates a clone invalidated by recombination.",
    "ncbi_link": "Gal4: 855828
HIS3: 854377
LexA: 948544
Rabaptin5: 9135
FIP200: 9821"
  },
  {
    "caption": "D FIP200 was immunoprecipitated (IP) from lysates of HeLa or HEK293A cells and probed for FIP200, Rabaptin5 (Rbpt5), and EEA1 (early endosome antigen 1) by immunoblotting. Input lysate (10%) was immunoblotted blotted parallel. As a negative control, the immunoprecipitation was performed using an anti-GAPDH antibody. E-H Lysates of HeLa cells transiently transfected with full-length FIP200-mCherry (FIP200-mCh) or a deletion mutant lacking the segment interacting with Rabaptin5 (∆280-440) were immuprecipitated with anti-mCherry (IP FIP200-mCh) or, as a control, with anti-FLAG antibodies (IP FLAG). Immunoprecipitates and input lysates (10%) were immunoblotted for mCherry and Rabaptin5 (E), ATG13 (F), or ULK1 (G). Co-immunoprecipitation of Rabaptin5, ATG13, and ULK1 with FIP200∆280-440 (FIP∆) was quantified in comparison to that with wild-type FIP200 (H; signals normalized to that of the immunoprecipitated protein;",
    "ncbi_link": "mCh: 
mCherry: 
Rabaptin5: 9135
FIP200: 9821"
  },
  {
    "caption": "HEK+Rbpt5 cells, untransfected or 24 h after transfection with mCherry-galectin3 (mCh-Gal3), mRuby3-galectin8 (mRuby-Gal8), mCherry-FIP200, or -ATG16L1 were analyzed upon chloroquine treatment by immunofluorescence microscopy for Rabaptin5 and mCherry-galectin3 or mRuby3-galectin8 (C), ubiquitin (Ub; D), p62 (E), mCherry-FIP200 (F), WIPI2 (G), mCherry-ATG16L1 (H), or LC3B (I). Scale bar, 10 µm. In the enlarged insets, arrowheads point out chloroquine-induced enlarged, ring-like early endosomes. Rabaptin5-positive enlarged endosomes positive for mCherry-galectin3 (Gal3) or mRuby3-galectin8 (Gal8) were quantified (C'; mean ± S.D.",
    "ncbi_link": "mCh: 
mCherry: 
mRuby: 
mRuby3: 
ATG16L1: 55054
Gal3: 3958
galectin3: 3958
Gal8: 3964
galectin8: 3964
Rbpt5: 9135
FIP200: 9821"
  },
  {
    "caption": "J, K HEK+Rbpt5 cells, untransfected or 24 h after transfection with mCherry-ATG16L1, were treated with 60 µM chloroquine for 0, 15 and 30 min and stained for Rabaptin5 and either WIPI2 or mCherry-ATG16L1. Manders' colocalization coefficients were determined, M1 showing the fraction of Rabaptin5-positive structures also positive for WIPI2 (J) or mCherry-ATG16L1 (K), and M2 showing the respective inverse (mean ± S.D. of three independent experiments;",
    "ncbi_link": "mCherry: 
ATG16L1: 55054
Rbpt5: 9135"
  },
  {
    "caption": "A HEK293A cells were transfected with nontargeting siRNA (siCtr) or siRNAs silencing Rabaptin5 (siRbpt5) or FIP200 (siFIP200) for 72 h and treated without (-) or with 60 µM chloroquine (+CQ) or 250 nM Torin1 for 150 min. Scale bar, 10 µm. Below, the efficiency of Rabaptin5 and FIP200 knockdown was assayed by immunoblotting using tubulin (Tub) as a loading control. B WIPI2 or LC3B puncta per cell were quantified for each condition (mean ± S.D. of three independent experiments; ANOVA: *P<0.05, **P<0.01). C",
    "ncbi_link": "Rabaptin5: 9135
Rbpt5: 9135
FIP200: 9821"
  },
  {
    "caption": "C HEK293A cells were transfected with siCtr or siRbpt5 as in A and incubated without or with 280 µM LLOMe for 150 min to induce lysophagy. Cells were fixed and immunostained for endogenous WIPI2 and LC3B. Scale bar, 10 µm. D WIPI2 or LC3B puncta per cell were quantified (mean ± S.D. of three independent experiments).",
    "ncbi_link": "Rbpt5: 9135"
  },
  {
    "caption": "A HEK293A cells were transfected with nontargeting siRNA (siCtr) or siRNAs silencing ATG13 (siATG13) for 72 h, treated without (-) or with 60 µM chloroquine (+CQ) for 150 minutes, and fixed and immunostained for endogenous WIPI2 and LC3B. Scale bar, 10 µm. Efficiency of ATG13 knockdown was assayed by immunoblotting below on the right using GAPDH as loading controls. B WIPI2 of LC3B puncta per cell were quantified for each condition (mean ± S.D. of three independent experiments; ANOVA: **P<0.01). C",
    "ncbi_link": "ATG13: 9776"
  },
  {
    "caption": "HEK293A cells were transfected with nontargeting siRNA (siCtr) or siRNAs silencing ULK1 (siULK1), ULK2 (siULK2), or both (siULK1+2) for 72 h, treated without (-) or with 60 µM chloroquine (+CQ) for 150 minutes, and fixed and immunostained for endogenous WIPI2 and LC3B. Scale bar, 10 µm. Efficiency of ULK1 knockdown was assayed by immunoblotting The efficiency of ULK2 knockdown was assayed by quantitative RT-PCR and the result is shown in panel C D WIPI2 of LC3B puncta per cell were quantified for each condition (mean ± S.D. of three independent experiments",
    "ncbi_link": "ULK1: 8408
ULK2: 9706"
  },
  {
    "caption": "B Co-immunoprecipitation was performed as in panel A using parental HEK293A cells and CRISPR/Cas9 knockout cells lacking FIP200 (FIP-KO). Anti-HA antibodies were used as a control (IP HA). On the right, HEK293A and FIP200 knockout cells were immunoblotted for FIP200 and as a loading control of tubulin (Tub). Signals were quantified and the ratios of mCherry-ATG16L1/Rabaptin5 normalized to that of HEK293A cells without chloroquine treatment",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
FIP: 9821
FIP200: 9821"
  },
  {
    "caption": "Lysates of HEK293A or HeLa cells transiently transfected with full-length mCherry-ATG16L1 (wt) or a mutant lacking the WD domain (∆WD; residues 1-319 of ATG16L1, precisely deleting only the WD40 repeats residues 320-607) were immunoprecipitated with anti-Rabaptin5 or anti-FLAG antibodies, and immunoblotted for Rabaptin5 and mCherry-ATG16L1 , or immunoprecipitated with anti-FIP200 or anti-HA antibodies Co-immunoprecipitation of ATG16L1∆WD with Rabaptin5 (C) was reduced to 6.6±2.1% and 3.4±2.1% in HEK293A and HeLa cells, respectively, relative to that of full-length ATG16L1 (signals normalized to the immunoprecipitated protein; mean ± S.D. deviation of three independent experiments each).",
    "ncbi_link": "mCherry: 
ATG16L1: 55054"
  },
  {
    "caption": "F Lysates of HeLa cells transiently transfected with myc-tagged wild-type Rabaptin5 (wt) or triple-alanine mutant (AAA) were immunoprecipitated with anti-myc (IP myc) or anti-FLAG antibodies (IP FLAG), and immunoblotted for myc and ATG16L1. Co-immunoprecipitation of ATG16L1 with Rabaptin5-AAA triple mutant was reduced to 1.5±1.2% relative to that with wild-type Rabaptin5 (signals normalized to that of the immunoprecipitated protein; mean ± S.D. of three independent experiments).",
    "ncbi_link": "myc: 
Rabaptin5: 9135"
  },
  {
    "caption": "A By immunoblot analysis, the levels of Rabaptin5 and as a loading control of tubulin (Tub) were assessed in wild-type HEK293A cells, HEK+Rbpt5 cells stably overexpressing Rabaptin5, and Rabaptin5-knockout cells without (Rbpt5-KO) or with stable re-expression of wild-type (Rbpt5-KO+wt) or AAA-mutant Rabaptin5 (Rbpt5-KO+AAA). B The same stable HEK293A-derived cell lines were treated without (-CQ) or with 60 µM chloroquine for 150 min (+CQ) and analyzed by immunofluorescence microscopy for WIPI2 or LC3B. Scale bar, 10 µm. C",
    "ncbi_link": "Rabaptin5: 9135
Rbpt5: 9135"
  },
  {
    "caption": "F, G HEK+Rbpt5 cells and Rabaptin5-knockout cells stably re-expressing wild-type (Rbpt5-KO+wt) or AAA-mutant Rabaptin5 (Rbpt5-KO+AAA) were transfected with mCherry-ATG16L1, treated with 60 µM chloroquine (CQ) for 0, 15 and 30 min, and analyzed by immunofluorescence microscopy for Rabaptin5, mCherry-ATG16L1, and WIPI2. Manders' colocalization coefficients were determined, M1 showing the fraction of Rabaptin5-positive structures also positive for mCherry-ATG16L1 (F) or WIPI2 (G) and M2 showing the inverse (mean ± S.D. of three independent experiments",
    "ncbi_link": "mCherry: 
ATG16L1: 55054
Rabaptin5: 9135
Rbpt5: 9135"
  },
  {
    "caption": "H Wild-type HEK293A cells, HEK+Rbpt5 cells, Rabaptin5-knockout cells without (Rbpt5-KO) or with stable re-expression of wild-type (Rbpt5-KO+wt) or AAA-mutant Rabaptin5 (Rbpt5-KO+AAA) were stained with lysotracker and with DAPI for nuclei. Scale bar, 10 µm. I The number of lysosomes (lysotracker-positive structures) per cell was quantified from cells as in panel C (mean ± S.D. of three independent experiments). Images for at least 15 cells per sample were quantified. The value for HEK+Rbpt5 cells is an underestimate, because the density of puncta makes them difficult to distinguish as separate structures.",
    "ncbi_link": "Rabaptin5: 9135
Rbpt5: 9135"
  },
  {
    "caption": "A HeLa cells were transfected with nontargeting siRNA (siCtr) or siRNAs silencing Rabaptin5 (siRbpt5) or FIP200 (siFIP200) for 72 h. The cells were infected with Salmonella by centrifugation at 500×g for 5min at 37°C and incubation for 10 min at 37°C, washed three times, and incubated in fresh culture medium containing gentamicin to prevent growth of extracellular bacteria for 0, 1, 3, or 6 h before lysis of the host cells and plating of the bacteria on LB agar plates at various dilutions to determine the number of live bacteria at the different time points, shown as a percentage of internalized cells after infection (mean ± S.D. of three independent experiments). The fractions of internalized bacteria alive 1 h after infection are shown separately in the middle (mean ± S.D. of three independent experiments; ANOVA: *P<0.05). On the right, the fraction of infected cells was determined for HeLa cells transfected with siRNAs and infected as above with Salmonella expressing GFP, washed, and immediately fixed for fluorescence microscopy and stained with anti-transferrin receptor and anti-LC3B as cellular markers. Z-stacks for >5'000cells/sample were acquired and analyzed in Fiji to determine the fraction of infected cells (mean ± S.D. of three independent experiments). The average number of bacteria per infected cell was identical (2.16, 2.11, and 2.12 bacteria per cell transfected with siCtr, siRbpt5, and siFIP200, respectively).",
    "ncbi_link": "Rabaptin5: 9135
Rbpt5: 9135
FIP200: 9821"
  },
  {
    "caption": "B Wild-type HEK293A, HEK+Rbpt5, Rbpt5-KO, Rbpt5-KO+wt, Rbpt5-KO+AAA, and FIP200-KO cells were infected with Salmonella and treated and analyzed as in panels A (mean ± S.D. of three independent experiments; ANOVA: *P<0.05, ****P<0.0001).",
    "ncbi_link": "Rbpt5: 9135
FIP200: 9821"
  },
  {
    "caption": "C Wild-type HEK293A, HEK+Rbpt5, Rbpt5-KO, Rbpt5-KO+AAA, and FIP200-KO cells were infected with Salmonella expressing GFP as in panel B, incubated in fresh culture medium containing gentamicin for 0, 5, 15, 30, and 60 min, fixed with methanol and immunostained for transferrin receptor (TfR) as a marker of early endosomes and for LC3B as a marker of autophagy. Salmonella were classified according to their association with a TfR- and/or LC3B-positive compartment - as illustrated on the top left (scale bar, 2 µm) - during the first hour after infection. In the absence of Rabaptin5, LC3-positive SCVs with early endosomal characteristics (containing TfR) were strongly reduced. (Mean ± S.D. of three independent experiments, analyzing >50 bacteria for each time point.)",
    "ncbi_link": "Rabaptin5: 9135
Rbpt5: 9135
FIP200: 9821"
  },
  {
    "caption": "(D-F) Quantification of the Rango-3 E gradients (top panels) and average cellular Rango-3 E (bottom) in involving untreated oocytes (controls) or oocytes injected with RanT24N mRNA, importin β(71-876) protein or treated with 20 µM IPZ. Data for each panel are from at least 2 separate experiments. Means ± SDs, t-test, oocyte numbers indicated in brackets.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(A) Quantification of chromosomal cargo gradients (top) and average Rango-3 E in oocytes injected with increasing concentrations of Ran mutant mRNA concentrations. Data from oocytes imaged side-by-side within one experiment. Means ± SDs, one-side ANOVA, Tukey's test. Numbers of analyzed oocytes are indicated in the brackets in the top panel and are identical for both panels.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(D) Quantification of the Rango-3 E gradients (top panels) and average cellular Rango-3 E (bottom) oocytes that were treated side-by-side by the injection of mRNA for Rango-3, alongside with buffer (controls) or 2000ng/µl mRNA for RanT24N or RanT24N, T42A. Means ± SDs, one-side ANOVA, Tukey's test, oocyte numbers indicated in brackets.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(D-F) Quantification of the RBP-3 gradients (top panels) and average cellular RBP-3 E (bottom) in separate experiments involving untreated oocytes (controls) or oocytes injected with RanT24N mRNA, importin β(71-876) protein or treated with 20µM IPZ. Means ± SDs, t-test, oocyte numbers indicated in brackets.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(A) Dose-dependent effects of IPZ on MI spindle assembly are shown by maximum z-projection images from confocal time-lapse imaging of oocytes obtained from transgenic histone H2B-EGFP mice stained with SiR-tubulin. Dashed circles indicate oocyte edges; scale bars, 10 µm.",
    "ncbi_link": "EGFP: 
histone H2B: "
  },
  {
    "caption": "(E) MI spindle formation in oocytes expressing CDK5RAP2-EGFP, histone H2B-mCherry and stained with SiR-tubulin matured in the presence of 15 µM IPZ. Representative still images of maximum z-projections are shown. Time in hh:mm is relative to GVBD. Scale bar, 10 µm.",
    "ncbi_link": "EGFP: 
histone H2B: 
mCherry: 
CDK5RAP2: 214444"
  },
  {
    "caption": "(H) Oocytes expressing CDK5RAP2-EGFP, histone H2B-mCherry and stained with SiR-tubulin were treated with 15 µM IPZ after being cultured for 5h in control media. Maximum intensity z-projections from confocal live-cell imaging are shown. Time in hh:mm is relative to GVBD, DMSO or 15 uM IPZ was added at time 5:00. Scale bars, 10 µm.",
    "ncbi_link": "EGFP: 
histone H2B: 
mCherry: 
CDK5RAP2: 214444"
  },
  {
    "caption": "(A) The rescue of the effects of 15 µM IPZ on MI spindles was examined in mouse oocytes expressing histone H2B-mCherry from microinjected mRNA, co-stained with SiR-tubulin and noninjected or injected with mRNAs coding for RanQ69L or hTPX2. Maximum intensity z-stack projections from confocal live-cell movies 30 min after GVBD, at metaphase I and anaphase I. Time in hh: mm is relative to GVBD. Scale bars, 10 µm.",
    "ncbi_link": "histone H2B: 
mCherry: 
Ran: 5901
hTPX2: 22974"
  },
  {
    "caption": "(A) The effects of RanT24N, T42A, and RanT24N on MI spindle assembly observed in maximum z-projection images from confocal time-lapse imaging of oocytes expressing CDK5RAP2-EGFP, histone H2B-mCherry and stained with SiR-tubulin. Time in hh:mm is relative to GVBD. Scale bar, 10 µm. (B, C) Live-cell imaging of oocytes as in (A) was used to quantify the effects of Ran mutant. Means ± SDs., Mann-Whitney test, oocyte numbers are indicated in brackets. ",
    "ncbi_link": "EGFP: 
histone H2B: 
mCherry: 
CDK5RAP2: 214444
Ran: 5901"
  },
  {
    "caption": "(D) MT intensity at MTOCs at the time of GVBD quantified from SiR-tubulin signal that was normalized to mean cytoplasmic SiR-tubulin signal. Mean of MT intensity on MTOCs was arbitrarily centered to 1 in the control group. Means ± SDs, Kruskal-Wallis, and Dunn's tests. 25 control oocytes with 264 MTOCs in total, 10 RanT24N-expression oocytes with 70 MTOCs in total and 19 RanT24N, T42A-expressing oocytes with 96 MTOCs in total were analyzed.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(F) Frequency and severity of MI spindle phenotypes in the oocytes expressing RanT24N or RanT24N, T42A. Oocyte numbers are shown in brackets.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(I) Detection of MTs and pericentrin-containing MTOCs by IF in control and RanT24N, T42A - expressing oocytes. Arrow indicates unaligned chromosome. (J) Quantification of chromosomal spread area in oocytes depicted in (I), Means ± SDs, Mann-Whitney test, oocyte numbers indicated in brackets. ",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(A). Maximum intensity z-stack projections of confocal IF images (DNA stain, indirect IF for tubulin and TPX2) in untreated oocytes (control), oocytes expressing RanT24N or injected with importin β(71-876). The representative of at least 5 experiments is shown.",
    "ncbi_link": "Ran: 5901"
  },
  {
    "caption": "(E) Western blot analysis with representative blot including NLRP3, caspase 1, IL-1β and actin levels in heart and liver tissues from wild-type and Zmpste24-/- mice.",
    "ncbi_link": "Zmpste24: 230709"
  },
  {
    "caption": "(F) NLRP3 and Caspase 1 transcript expression levels were determined in heart and liver tissues by real-time quantitative RT-PCR. n=5 for Zmpste24+/+ and n=5 for Zmpste24-/- groups respectively. ***P < 0.001, **P < 0.005, wild-type vs Zmpste24-/- mice. Data are showed means ± SD, n = 4 mice per group.",
    "ncbi_link": "Caspase 1: 12362
NLRP3: 216799
Zmpste24: 230709"
  },
  {
    "caption": "(F) Kaplan-Meier graph showing a significant increase in the maximum lifespan in WT mice compared with Zmpste24-/- mice. N=7 per group.",
    "ncbi_link": "Zmpste24: 230709"
  },
  {
    "caption": "(H) Analysis of serum concentrations of IL-1β measured by ELISA. N=6 per group. Data are shown as means ± SD. ***P < 0.001, wild-type vs Zmpste24-/- mice; aaaP < 0.001; vehicle vs MCC950.",
    "ncbi_link": "Zmpste24: 230709"
  },
  {
    "caption": "Top, average colon  length of WT and QSOX1  KO mice  following indicated treatments. For untreated mice, colon  lengths were calculated for 3 WT and 3 KO. For treated mice, lengths were calculated from 5 mice  except for the DSS-treated WT, for which 3 mice  were analyzed. Error bars are standard deviation. Statistical analysis was performed using Tukey multiple comparison of means (** p<0.01). Administration of QSOX1  inhibitory antibody MAb316.1 (αQSOX1), did not enhance the sensitivity of WT colons  to DSS  (p>0.4 for MAb316.1-treated WT vs. WT control antibody (IgG)-treated; p>0.5 for MAb316.1-treated WT vs. WT without antibody treatment). Bottom, representative images of colons following DSS  treatment. Scale bar is 1 cm.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "Representative TEM  micrographs of about a hundred collected from 3 mice  of each genotype show large and well-packed goblet cell granules   in WT and QSOX1  KO colons. Scale bar is 5 µm.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "Alcian blue and PAS staining  of reduced guanidine-insoluble mucins  from WT and QSOX1  KO mice, separated on a 6% polyacrylamide  gel. Data information: each lane corresponds to a sample from one mouse.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "Muc5b  fluorescent immunoblot  of WT and QSOX1  KO lung  lavage samples separated on agarose  gels. Data information: each lane corresponds to a sample from one mouse.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "Western blot  analysis of blood Vwf  from WT and QSOX1  KO mice  separated on agarose  gels. Data information: each lane corresponds to a sample from one mouse.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "QSOX1 immunofluorescence  (green) in control (siControl) and QSOX1  knockdown (siQSOX1) MDA-MB-231  cells. Blue is DAPI staining  of nuclei. Scale bar is 20 µm. Data information: The results described in are representative of 3 experiments that were performed.",
    "ncbi_link": "QSOX1: 5768"
  },
  {
    "caption": "Western blot  analysis of the MUC2  N-terminal region and indicated cysteine mutants in supernatants of transfected cell cultures. No differences in disulfide-mediated dimerization  were observed for any MUC2  variant between siC (siControl) and siQ (siQSOX1). Data information: The results described in G are representative of 3 experiments that were performed.",
    "ncbi_link": "MUC2: 4583
QSOX1: 5768"
  },
  {
    "caption": "Western blot analysis of colon epithelial cell  lysates from WT and QSOX1  KO mice. Lysates were treated with   PEG-mal  2  kDa or NEM  as indicated above each blot  and probed using antibodies to St6gal1. As for panel A but using antibodies to St3gal1. As for panel A but using antibodies to B3galt5. Data information: For the experiments in panels A-C, equal amounts of total protein were applied to each gel lane, and no reducing agent was added. Experiments were repeated 3 times with fresh new lysates, and representative blots  are shown.",
    "ncbi_link": "QSOX1: 104009"
  },
  {
    "caption": "E WT and C2βD1212A/D1212A mice were subjected to  thromboembolic stroke model. Representatives T2-weighted MRI of coronal section taken 24 hours after the onset of in situ clot formation by α-thrombin were shown. Graph quantification of infarct volume measurements. Data represent mean ± SEM (n=23-25 mice  per group; **p<0.01, Unpaired t-test).",
    "ncbi_link": "C2β: 240752"
  },
  {
    "caption": "WT and C2βD1212A/D1212A mice were subjected to tMCAO followed by 24h of reperfusion. (B) Protein expression of TNFα, IL-1β and IL-6. Data represent mean ± SEM (n=4 mice per group; *p=0.05; Mann-Whitney test). Data represent mean ± SEM (n=5-7 mice per group; **p<0.01; Mann-Whitney test).",
    "ncbi_link": "C2β: 240752"
  },
  {
    "caption": "A Gene expression of TNFα (n=8-10 mice for WT and n=6 mice  for  C2βD1212A/D1212A), IL-1β (n=8 mice for WT and n=10-12  mice for C2βD1212A/D1212A), IL-6 (n=8 mice for WT and n=10-12 mice for C2βD1212A/D1212A) and VCAM-1  (n=8-10 mice for WT and n=10 mice for C2βD1212A/D1212A) after 1 hour of ischemia without reperfusion (right panel). Gene expression of IL-6 (n=10-12 mice for WT and n=8 mice for C2βD1212A/D1212A) and  VCAM-1 (n=12 mice for WT and n=10mice for C2βD1212A/D1212A) after 1 hour of ischemia followed by 4 hours of reperfusion (bottom, left panel) on WT and C2βD1212A/D1212A mice. The mRNA levels are given as the fold increase normalized to PGK1  relative to the healthy contralateral hemisphere of WT mice. Data represent mean ± SEM (***p<0.001, **p<0.01, *p<0.05, Mann-Whitney test or unpaired t-test, as accordance).",
    "ncbi_link": "IL-1β: 16176
IL-6: 16193
PGK1: 18655
C2β: 240752
TNFα: 21926
VCAM-1: 22329"
  },
  {
    "caption": "Representative photographs of coronal brain sections and graph quantification of  infarct volume (dashed white line) measurements in bone marrow  (BM) chimeric mice 24 hours after tMCAO. WT>WT: transplantation  of WT BM into WT hosts; C2βD1212A>WT: transplantation  of C2βD1212A/D1212A BM into WT hosts;  C2βD1212A>C2βD1212A: transplantation of C2βD1212A/D1212A BM into C2βD1212A/D1212A hosts; WT> C2βD1212A transplantation of WT BM into kinase-dead hosts. Data represent mean ± SEM; n=13-16 mice per group; *p<0.05 **p<0.01; ***p<0.001 vs WT>WT, Mann-Whitney test or unpaired t-test, as accordance.",
    "ncbi_link": "C2β: 240752"
  },
  {
    "caption": "B Analysis of APPL1, EEA1, LAMP1 and Rab11a staining in sh-Control and sh-PI3KC2β hCMEC/D3 cells. White dotted lines delineate cells; Scale bar, 10µm; nuclei are shown in blue (DAPI).",
    "ncbi_link": "PI3KC2β: 5287"
  },
  {
    "caption": "(A) Representative VE-cadherin staining and graph quantification of fluorescence intensity normalized to total number of cells per field (DAPI  labelling) in sh-Control and sh-PI3KC2β hCMEC/D3 in resting condition and after 24 hours activation with 25 ng/ml of TNFα. Control normalized to 100%. Scale bar, 15 µm. Data represent mean ± SEM of cell fields randomly selected (dots n=14-19). Data are collected from 4-5 independent experiments; ***p<0.001, unpaired t-test.",
    "ncbi_link": "PI3KC2β: 5287"
  },
  {
    "caption": "A Representative  images of PI3P and PI(3,4)P2 labeling and quantification using mCherry-FYVEHRS and GFP-PH(TAPP1) probes respectively in sh-Control or sh-PI3KC2β hCMEC/D3. Scale bar, 10 µm. Nuclei are shown in blue (DAPI). Staining intensity was quantified by ImageJ  software and normalized to total  number of cells (DAPI labelling) per field. Data represent mean ± SEM of cell fields randomly selected for PI3P (dots n=21) and for PI(3,4)P2 (dots n=14-16). Data were collected from at least 5 independent experiments; ***p<0.001, unpaired t-test with Welch's correction.",
    "ncbi_link": "PI3KC2β: 5287"
  },
  {
    "caption": "C Graph quantification of APPL1-, EEA1- and Rab11- endosomes colocalized with mCitrin-VE-cadherin in sh-Control and sh-PI3KC2β hCMEC/D3 cells. Data are shown as percentage of total count  endosomes per cell. Data are expressed as mean ± SEM (n=33-35 cells for APPL1 and EEA1 endosomes and n=16-18 cells for Rab11 endosomes; 3 independent experiments); **p<0.001, Mann-Whitney test or unpaired t-test, as accordance.",
    "ncbi_link": "PI3KC2β: 5287"
  },
  {
    "caption": "D Representative confocal microscopic images of VE-cadherin immunostaining in sh-Control cells, sh-PI3KC2β cells or sh-PI3KC2β cells transduced with Rab11S25N (Rab11-DN). Graph quantification of VE-cadherin; control normalized to 100%. Scale bar, 10 µm. Data represent mean ± SEM of cell fields randomly selected (dots n=6-9). Data are collected from at least 3 independent experiments; **p<0.01 Mann-Whitney test.",
    "ncbi_link": "PI3KC2β: 5287
Rab11: 8766
Rab11S25N: 8766"
  },
  {
    "caption": "(C) Temporal analysis of antigen-specific CD8+ T cell responses. Peripheral blood was obtained on days 4, 7, 14, 21, 42 and 88 post-immunisation with WT (triangles; n=3-9), CSPSIINFEKL (orange squares; n=4-8) or UIS4SIINFEKL (blue circles; n=4-10) sporozoites, or no parasites (diamonds; n=2-5) and stained for Kb-SIINFEKL+ CD11ahi CD8+ T cells. Line graph shows mean values (±SEM) from representative experiments. (*, p<0.05; **, p<0.01; ***, p<0.001; Welch's t-test comparing CSPSIINFEKL and UIS4SIINFEKL). See Appendix Table S1 for the number of mice used per timepoint and per group. See Appendix Table S4 for exact p-values.",
    "ncbi_link": "CSP: 55148143
UIS4: 55148315"
  },
  {
    "caption": "(D-H) C57BL/6 mice (n=4 per group), which received 2x106 CFSE-labelled OT-I splenocytes, were immunised with 10,000 γ-radiation attenuated WT, CSPSIINFEKL or UIS4SIINFEKL sporozoites intravenously. 5 days later, mice were sacrificed, spleens harvested and splenocytes assessed for (D) CFSE dilution of CD8+ T cells, (E) CFSE dilution of antigen experienced Kb-SIINFEKL+ CD11ahi CD8+ T cells and stained ex vivo (F-H) for effector CD8+ T cell surface markers. Shown are flow cytometry plots of Kb-SIINFEKL co-staining with markers of effector phenotypes: (F) CD11ahi, (G) CD62Llo and (H) CD49dhi.",
    "ncbi_link": "CSP: 55148143
UIS4: 55148315"
  },
  {
    "caption": "(B- C57BL/6 mice received 10,000 γ-radiation attenuated WT, CSPSIINFEKL or UIS4SIINFEKL sporozoites, either intravenously (n=6-8 mice per group) or (E- intradermally (n=4 mice per group). Additional control mice did not receive sporozoites (n=6-8 intravenously, n=4 intradermally). Spleens and livers were harvested either at day 14 (n=5 livers and n=6 spleens for intravenous immunisation) or day 42 (n=8 for intravenous immunisation), and IFN-γ-secreting lymphocytes following restimulation ex vivo with SIINFEKL peptide were quantified. Flow cytometry plots show representative percentages of CD8+ T cells co-stained with IFN-γ and CD11a (B, E).",
    "ncbi_link": "CSP: 55148143
UIS4: 55148315"
  },
  {
    "caption": "(D) Protective efficacy as measured by quantitative real-time PCR. Groups of mice were vaccinated as described and challenged 19 days later with 10,000 WT (n=7 non-vaccinated, n=9 vaccinated), CSPSIINFEKL (n=6 non-vaccinated, n=4 vaccinated) or UIS4SIINFEKL sporozoites (n=3 non-vaccinated, n=11 vaccinated). 42 hours later livers were removed, and parasite load was assessed by qPCR. Plots show the relative parasite load of mice in each condition (**, p<0.01; Mann-Whitney U test). See Appendix Table S4 for exact p-values. Data information: Data are representative of two experiments performed with scatter plots showing mean values (±SEM).",
    "ncbi_link": "CSP: 55148143
UIS4: 55148315"
  },
  {
    "caption": "(A) Quantification of the amount of LC3‐II protein in mouse Rab‐knockdown cells. Representative blots are shown in supplementary Fig S1C online. Error bars represent the means and s.e.m. of three independent experiments.",
    "ncbi_link": "Rab: 15463"
  },
  {
    "caption": "(B) Quantification of the amount of p62 protein in candidates Rab‐knockdown cells. Representative blots are shown in supplementary Fig S1D online. Error bars represent the means and s.e.m. of three independent experiments.",
    "ncbi_link": "Rab: 15463"
  },
  {
    "caption": "(C,D) Control and Rab12‐knockdown MEFs were cultured under N or S conditions, fixed and then immunostained with the antibodies indicated. Representative images are shown in supplementary Fig S2 online. The mean numbers of LC3‐positive (C) or Atg16L1‐positive (D) dots per cell are shown. Error bars represent the means and s.e.m. of representative data (n≥80) from three independent experiments.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(E) MEFs that had been transfected with the control siRNA or Rab12 siRNA were cultured as in (C,D), and their lysates were analysed by immunoblotting with the antibodies indicated.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(G) Control and Rab12‐knockdown MEFs were cultured under N or S conditions in the absence or presence of 100 μM bafilomycin A1 for 1 h. Cell lysates were analysed by immunoblotting with the antibodies indicated, and the intensity of the LC3‐II band was quantified. The normalized amount (arbitrary units) of LC3‐II in lanes 1, 2, 3, 4, 5 and 6 is 1.0, 2.3, 4.3, 0.9, 1.6 and 3.8, respectively.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(H) MEFs transiently expressing mStr‐Rab12 were cultured under starved conditions and immunostained with the antibodies indicated. Scale bar, 20 μm. MEFs, mouse embryonic fibroblasts; N, nutrient‐rich; S, starved; siRNA, short interfering RNA. *P0.05; **P0.01; ***P0.005.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(A) Control and Rab12‐knockdown MEFs were cultured under nutrient‐rich or starved conditions, fixed and then immunostained with the antibodies indicated. Scale bar, 20 μm.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(B) Control and Rab12‐knockdown MEFs were cultured as in (A), and their lysates were analysed by immunoblotting with the antibodies indicated.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(C) Lysates of MEFs that had been transfected with control or Rab12 siRNA were analysed by immunoblotting with the antibodies indicated.",
    "ncbi_link": "Rab12: 19328"
  },
  {
    "caption": "(A) MEFs transiently co‐expressing Myc‐PAT4 and mStr‐Rab12 were immunostained with anti‐Myc antibody.",
    "ncbi_link": "Rab12: 19328
PAT4: 234967"
  },
  {
    "caption": "(B) MEFs transiently expressing Myc‐PAT4 were immunostained with the antibodies indicated. Scale bars, 20 μm.",
    "ncbi_link": "PAT4: 234967"
  },
  {
    "caption": "(C) Total cell lysates and surface biotinylated proteins from MEFs stably expressing HA‐PAT4 were analysed by immunoblotting with the antibodies indicated.",
    "ncbi_link": "PAT4: 234967"
  },
  {
    "caption": "(D) Lysates of MEFs stably expressing HA‐PAT4 that had been transfected with control or Rab12 siRNAs were analysed by immunoblotting with the antibodies indicated.",
    "ncbi_link": "Rab12: 19328
PAT4: 234967"
  },
  {
    "caption": "(F) PAT4 mRNA levels from MEFs transfected with control or Rab12 siRNA as revealed by reverse‐transcription PCR analyses. Gapdh was used as an internal control.",
    "ncbi_link": "Rab12: 19328
PAT4: 234967"
  },
  {
    "caption": "(G) Total cell lysates and surface biotinylated proteins from MEFs stably expressing HA‐PAT4 that had been transfected with control or Rab12 siRNA were analysed by immunoblotting with the antibodies indicated. Note that the amounts of plasma‐membrane‐localized PAT4 protein and TfR protein were higher in Rab12‐knockdown MEFs, whereas the total amounts of EGFR protein and plasma membrane‐localized EGFR protein in these cells were slightly lower, but the mechanisms responsible for these changes are unknown. GAPDH, glyceraldehyde‐3‐phosphate dehydrogenase; MEFs, mouse embryonic fibroblasts; PAT4, proton‐coupled amino‐acid transporter 4; siRNA, short interfering RNA.",
    "ncbi_link": "Rab12: 19328
PAT4: 234967"
  },
  {
    "caption": "B. ERK71 mutants have elevated triacylglycerol (TAG) levels (N=4 replicates of ≥10 larvae/ replicate for each genotype). C. Fat body specific depletion of ERK7 by RNAi (BDSC 56939) leads to increased TAG levels (N=4 replicates of 10 larvae/replicate for each genotype). ",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D. Representative immunofluorescent images of lipid droplet (LipidTOX) and nuclear (DAPI) staining in control and ERK71 mutant fat bodies of third instar larvae. Scale bar: 50 µm. E. ERK71 mutant fat body cells contain more lipid droplets than control cells (N=30 cells for each genotype). ",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "F. After fed [13C]glucose, the ERK71 mutant fat bodies display elevated [13C]TAG/PE and unlabeled TAG/PE molar ratios (measured by mass spectrometry-based lipidomics, N=3 replicates of 15 fat bodies/replicate, TAG=triacylglycerol, PE=phosphatidylethanolamine)",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "G. ERK7 overexpression in the fat body results in reduced TAG levels, while kinase-dead (K54R) and activation loop phosphorylation-deficient (T190A/Y192F) mutants of ERK7 do not influence the TAG storage (N=4 replicates of ≥10 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "H- ERK7 expressing, GFP-marked, fat body clone (H, marked by yellow dotted line; scale bar: 50 µm) visualized by LipidTOX staining (N=11 for control and 4 for ERK7 overexpression).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "ERK7 expressing, fat body clone contains less (I) and smaller (J) lipid droplets than control cells (N=11 for control and 4 for ERK7 overexpression).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "K. qRT-PCR based expression analysis of ERK7 from fat bodies of w1118 larvae upon 6 h starvation. Expression of RP49 was used for normalization (N=3 replicates of 10 fat bodies/replicate for each genotype).",
    "ncbi_link": "RP49: 
ERK7: 31877"
  },
  {
    "caption": "A. Fatty acid composition of total lipids in CG>control and CG>ERK7 larvae, measured by gas chromatography (N=3 replicates of 15 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "C. Amount of glucose-derived [13C]-labeled carbons incorporated into the TAG pool of control and CG>ERK7 fat bodies (N=3 replicates of 15 fat bodies/replicate for each genotype and diet).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D. Ectopic ERK7 expression in the fat body results in elevated hemolymph glucose levels (N=3 replicates of 15 larvae/replicate for each genotype). E. Circulating glucose levels are decreased in ERK71 mutants (N=4 replicates of 15 larvae/replicate for each genotype). ",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "A. Four-way plot (t-statistics) presenting the ERK7-dependent fasting-responsive genes (adj.p.val < 0.05). Dark blue indicates significant in both comparisons; dark turquoise, significant in one comparison; light turquoise, not significant.",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "E, F. Expression analysis of Seipin, Agpat3, ATPCL, fabp, Lip4 and CG34448 by qRT-PCR. RP49 was used for normalization (N=3 replicates of ≥10 larvae/replicate for each genotype).",
    "ncbi_link": "RP49: 
Agpat3: 39820
ATPCL: 36760
CG34448: 5740554
fabp: 3772232
Lip4: 34450
Seipin: 31245"
  },
  {
    "caption": "A. Weight of control and ERK71 mutant larvae at 72h after egg deposition (AED) (N=4 replicates of 12 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "B. Pupariation kinetics of control and ERK71 mutants (N=4 replicates of 30 larvae/replicate for each genotype). p<0.0001, analyzed by Log-rank test.",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "C. ERK71 mutants fail to suppress growth upon 24 h of starvation (N≥4 replicates of 15 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D. ERK71 mutant larvae (N=4 replicates of 24 larvae/replicate for each genotype, p<0.01 analyzed by Log-rank test) are sensitive to nutrient deprivation.",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "Fat body specific knockdown of ERK7 by RNAi (BDSC 56939) leads to a moderately accelerated pupariation rate (E, p<0.001 analyzed by Log-rank test, N=8 replicates of 30 larvae/replicate for each genotype)",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "F. Fat body specific knockdown of ERK7 by RNAi (BDSC 56939) leads to an increase in larval weight at 72h AED (F, N=5 replicates of 15 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "G. A representative image showing that fat body-specific overexpression of ERK7 by the CG-GAL4 driver (CG>ERK7) impairs larval growth. Scale bar: 0.5 mm.",
    "ncbi_link": "ERK7: 31877
GAL4: 855828"
  },
  {
    "caption": "H. Ectopic expression of ERK7 leads to delayed pupariation (p<0.0001, analyzed by Log-rank test), while kinase-dead (K54R) and activation loop phosphorylation-deficient (T190A/Y192F) mutants of ERK7 do not influence pupariation rate (N=4 replicates of 30 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "I. In contrast to ERK7 wt, kinase-dead (K54R) and activation loop phosphorylation-deficient (T190A/Y192F) mutants of ERK7 do not influence the pupal volume (N=4 replicates of 10 pupae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "A. Representative immunofluorescent images of control and ERK71 mutant fat bodies with DAPI staining to visualize nucleus. Scale bar: 30 µm. B, C. ERK71 mutant fat bodies display increased nuclear area (B, N>160 cells, obtained from 5 independent fat bodies) and increased nucleolar/nuclear area ratio (C, N>80 cells for nucleolus/nucleus ratio, obtained from 5 independent fat bodies), when compared to control fat bodies.",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D-F. ERK7 expressing fat body clones (D, marked by GFP, scale bar: 20 µm) display reduced nuclear area (E) and reduced nucleolar/nuclear area ratio (F), when compared to control cells. Nuclei were visualized by DAPI staining, nucleoli were visualized by anti-Fibrillarin antibodies (N=10).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "G, H. Expression analysis of Pol I (G) and Pol III (H) target RNAs by qRT-PCR. Expression of CDK7 was used for normalization (N=3 replicates of 10 fat bodies/replicate for each genotype).",
    "ncbi_link": "CDK7: 31441
Pol III: 39941
Pol I: 36617"
  },
  {
    "caption": "B. Representative immunofluorescent images of PWP1 localization in fat bodies of ERK71 mutant and control third instar larvae. Scale bar: 20 µm. C. PWP1 localization displays increased nucleolar/nuclear ratio in ERK71 mutant fat bodies compared to control (N=20 cells from 5 independent fat bodies per genotype). ",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D. Representative immunofluorescent images of PWP1 localization in fat bodies of third instar larvae. ERK7 overexpression (GFP marked clones) alters the subcellular localization of PWP1. Scale bar: 30 µm. E. PWP1 localization displays reduced nuclear/cytoplasmic ratio in ERK7 overexpressing clones, compared to control cells (N=10 cells from at least 8 different fat bodies per genotype). ",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "F. Fat body specific depletion of PWP1 by RNAi leads to decreased TAG levels (N=4 replicates of ≥10 larvae/replicate for each genotype).",
    "ncbi_link": "PWP1: 36150"
  },
  {
    "caption": "G. Representative immunofluorescent images of fat bodies in a genetic epistasis experiment using ERK7 and PWP1 fat body (CG-GAL4) knockdown with LipidTOX staining and DAPI to visualize lipid droplets and nucleus, respectively. Scale bar: 50 µm. H, I. Fat body specific knockdown of PWP1 suppresses increased lipid droplet number (H; N>30 cells per genotype) and increased nuclear area (I; N>45 cells per genotype) caused by ERK7 knockdown (BDSC 56939). ",
    "ncbi_link": "ERK7: 31877
GAL4: 855828
PWP1: 36150"
  },
  {
    "caption": "A, B. Expression of sugarbabe is downregulated in fat bodies upon knockdown of PWP1 (A) and ectopic expression of ERK7 (B) (N=3 replicates of 10 fat bodies/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877
PWP1: 36150
sugarbabe: 36424"
  },
  {
    "caption": "C. ERK71 mutants fail to maximally downregulate sugarbabe expression upon fasting (N=4 replicates of 10 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877
sugarbabe: 36424"
  },
  {
    "caption": "D. Representative immunofluorescent images of fat bodies in a genetic epistasis experiment using ERK71 and sug mutants (sug17Δ/Df(2R)Exel7123) with LipidTOX and DAPI staining to visualize lipid droplets and nucleus, respectively. Scale bar: 50 µm. E. sug mutant (sug17Δ/Df(2R)Exel7123) suppresses increased lipid droplet number observed in ERK71 mutants (N>20). ",
    "ncbi_link": "ERK7: 31877
sug: 36424"
  },
  {
    "caption": "F. Ectopic sugarbabe expression in the fat body partially rescues TAG levels in the CG>ERK7 larvae (N=4 replicates of ≥10 larvae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877
sugarbabe: 36424"
  },
  {
    "caption": "G. sug mutant (sug17Δ/Df(2R)Exel7123) suppresses increased nuclear size phenotype of ERK71 mutant fat body cells (N ≥25 cells per genotype).",
    "ncbi_link": "ERK7: 31877
sug: 36424"
  },
  {
    "caption": "Ectopic Sugarbabe expression in the fat body partially restores the pupariation rate (H) (p<0.001 for the rescue, analyzed by Log-rank test, N=4 replicates of 30 larvae/replicate for each genotype) of CG>ERK7 larvae",
    "ncbi_link": "ERK7: 31877
Sugarbabe: 36424"
  },
  {
    "caption": "I. Ectopic Sugarbabe expression in the fat body partially restores the pupal volume of CG>ERK7 larvae (I) (N=4 replicates of 10 pupae/replicate for each genotype).",
    "ncbi_link": "ERK7: 31877
Sugarbabe: 36424"
  },
  {
    "caption": "J. Addition of 20% sucrose improves the growth rate and survival of CG>ERK7 larvae. Pupariation kinetics of CG>ERK7 larvae on 20% yeast or 20% yeast + 20% sucrose diet (p<0.0001 for the rescue, analyzed by Log-rank test, N=4 replicates of 30 larvae/replicate for each genotype and diet).",
    "ncbi_link": "ERK7: 31877"
  },
  {
    "caption": "D. Table showing the type of movement found for wild-type, mutant 2, mutant 5, and mutant 13 in a modified single-molecule assay with and without ATP. Classification of type of movement is based on two repetitions of different dynein preparations.",
    "ncbi_link": "dynein: 853928"
  },
  {
    "caption": "E. Microtubule stimulated ATPase activity of wild-type (grey), mutant 2 (red), mutant 5 (orange), and mutant 13 (purple). F. Bar plot of basal ATPase activity of wild-type (grey), mutant 2 (red), mutant 5 (orange), and mutant 13 (purple). Data information: Error bars show standard deviation of three repetitions of different dynein preparations.",
    "ncbi_link": "dynein: 853928"
  },
  {
    "caption": "E and F, Naïve WT CD4+CD62Lhi T cells were cultured under Th17  polarizing conditions. On day 3, cells were transfected with control or siRNA targeting Batf, rested overnight, used for total RNA isolation to assess gene expression (E), or restimulated with anti-CD3  for 24 h to measure cytokine production by ELISA  (F). Data information: , mean ± s.e.m. of 3-5 independent experiments (*p<0.05; two-sided t-test or one-way ANOVA followed by Tukey's test). RQ, relative quantification.",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "Naïve CD4+CD62Lhi T cells  from IL-17a  reporter mice  (Il17aeGFP) were cultured under Th17    polarizing conditions. On day 5,  eGFP+/IL-17a+ cells were sorted and cultured for two additional rounds in the presence of anti-CD3  alone (TCR(R3)) or Th17   polarizing cytokines (Th17(R3)) (G) Data information: Data are representative of 3-5 independent experiments",
    "ncbi_link": "eGFP: 
IL-17a: 16171
Il17a: 16171"
  },
  {
    "caption": "WT and Batf  KO mice  were orally infected by gavage with 2x109 cfu/ml of Citrobacter rodentium (Cr) expressing GFP  quantification of the signal (O) at the indicated time points. Data information: mean ± s.e.m. of n=5-6 mice  (O) (*p<0.05; two-sided t-test or one-way ANOVA followed by Tukey's test).",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "WT and Batf  KO mice were orally infected by gavage with 2x109 cfu/ml of Citrobacter rodentium  (Cr) expressing GFP Cr  infected WT and Batf  KO were sacrificed on day 4 and day 10. Cells were isolated from the colon, re-stimulated with PMA  and ionomycin, and stained  intracellularly for  flow cytometric analysis of cytokine production  and Foxp3 expression  presented as density plots (P). Data are gated on viable CD4+TCRβ+. Data information: Data are representative of two independent experiments",
    "ncbi_link": "GFP: 
Batf: 53314"
  },
  {
    "caption": "Naïve WT and Batf  KO CD4+CD62Lhi T cells  were cultured under Th17  polarizing conditions for 5 days. ChIP-seq for transcription factor (Batf) and histone modifications (H3K4me3, H3K27me3, and H3K27ac) was performed using day 5 WT and Batf  KO Th17  cells (A Data information: Data are representative of two independent experiments with similar results (A,",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "J, Naïve WT-2BiT and Batf  KO-2BiT CD4+CD62Lhi T cells  were cultured under Th17  polarizing conditions. IL-2-Thy1.1 production comparing WT-2BiT and Batf  KO-2BiT cells was measured by  flow cytometry at the indicated  time points and frequencies of positive cells determined. Data information: Data are representative of or mean ± s.e.m. of 3-5 independent experiments (*p<0.05; two-sided t-test).",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "ChIP-seq  for Stat3  and Stat5  was performed after 1 h of IL-6 and IL-2 stimulation, respectively, using WT and Batf  KO cells that were cultured under Th17  polarizing conditions for 5 days. Histograms show Batf, Stat3, and Stat5 binding  occupied around ±1 kb of peak centers of co-bound Stat3-Stat5  sites that were annotated near Th1, Th17, or Treg-specific genes (C). Data information: Data are mean ± s.e.m. representative of two independent experiments with similar results (c (*p<0.05; two-sided t-test).",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "D, ChIP-seq  for Stat3  and Stat5  was performed after 1 h of IL-6 and  IL-2 stimulation, respectively, using WT and Batf  KO cells that were cultured under Th17  polarizing conditions for 5 days. Tracks show Batf, Stat5, and Stat3 ChIP-seq data compared between WT and Batf  KO Th17  in the indicated gene loci (WT, grey; Batf  KO, red). Red arrows indicate differential Stat5 binding  comparing WT and Batf  KO cells (D). Data information: Data are mean ± s.e.m. representative of two independent experiments with similar results d), or (*p<0.05; two-sided t-test).",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "B, Naïve WT and Batf  KO CD4+CD62Lhi T cells were cultured under Th17  polarizing conditions for 5 days. The kinetics of Ets1  and Runx1 gene expression was assessed by RT-PCR  in the indicated time points (data normalized to naïve WT cells). Data information: Data are mean ± s.e.m. of 3 independent experiments (B) (*p<0.05; two-sided t-test). RQ, relative quantification.",
    "ncbi_link": "Batf: 53314
Ets1: 23871
Runx1: 12394"
  },
  {
    "caption": "Tracks show Ets1  and Runx1 ChIP-seq data from WT and Batf  KO Th17-polarized cells at the indicated gene loci (D; WT, grey; Batf  KO, red). Arrows indicate differential Ets1  and Runx1 binding  with (red) or without (blue) the presence of Batf binding  comparing WT and Batf  KO cells. Ets1  (E) or Runx1  (F) peaks from WT Th1, Treg, or both (Th1-Treg) were integrated with enriched Ets1  or Runx1  peaks in Batf  KO compared to WT Th17  cells (Fig. 4C) to separate peaks into unique and overlapping clusters.",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "Naïve WT and Batf  KO CD4+CD62Lhi T cells cultured under Th17-polarizing conditions were treated with or without 1 uM Stat5  inhibitor. On day 5, cells were harvested and used for RNA extraction to assess  gene expression (A; data were normalized to WT DMSO; Foxp3, unstimulated; Il17a  and Ifng, 6 h 2 ug/ml anti-CD3  restimulation) Data information: Data are mean ± s.e.m. of 4 independent experiments. (*p<0.05; two-sided t-test or one-way ANOVA followed by Tukey's test). a.u., arbitrary unit.",
    "ncbi_link": "Batf: 53314
Foxp3: 20371
Ifng: 15978
Il17a: 16171"
  },
  {
    "caption": "Naïve WT and Batf  KO CD4+CD62Lhi T cells cultured under Th17-polarizing conditions were treated with or without 1 uM Stat5  inhibitor. restimulated with 2 ug/ml anti-CD3  for 24 h to assess  cytokine production  by ELISA (B). Data information: Data are mean ± s.e.m. of 4 independent experiments. (*p<0.05; two-sided t-test or one-way ANOVA followed by Tukey's test). a.u., arbitrary unit.",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "Naïve WT and Batf  KO CD4+CD62Lhi T cells cultured under Th17-polarizing conditions were treated with or without 1 uM Stat5  inhibitor. WT and Batf  KO Th17-polarized cells were collected on day 5 of culture and used to performed ChIP using antibodies to Stat5, Batf, Ets1, Runx1, Stat3  and p300  (C). Data information: Data are mean ± s.e.m. of 4 independent experiments. (*p<0.05; two-sided t-test or one-way ANOVA followed by Tukey's test). a.u., arbitrary unit.",
    "ncbi_link": "Batf: 53314"
  },
  {
    "caption": "Naïve CD4+CD62Lhi T cells from  IL-17a reporter mice  (Il17aeGFP) were cultured under Th17  polarizing conditions. On day 5,  eGFP+/IL-17a+ cells were sorted (Th17(R1)) and cultured for two additional rounds in the presence of anti-CD3  alone (TCR(R3)) or Th17  polarizing cytokines (Th17(R3)). Ets1,Runx1, and Stat5 binding  at the indicated genomic regions by ChIP-qPCR  (C). Data information: Data are mean ± s.e.m. of 3 independent experiments. (*p<0.05; **p<0.01; one-way ANOVA followed by Tukey's test). ",
    "ncbi_link": "eGFP: 
IL-17a: 16171
Il17a: 16171"
  },
  {
    "caption": "Detection of NRPB2WT-FLAG, NRPB2P979S-FLAG and NRPB2Y732F-FLAG protein by western blotting in NRPB2WT-FLAG Col-0, NRPB2P979S-FLAG Col-0 and NRPB2Y732F-FLAG Col-0 plants. Untagged NRPB2 (Col-0) was used as a negative control. Histone H3 was used as an internal control and total protein level detected by stain-free blot was used as a loading control. Quantification was done by normalizing to the loading control and anti-H3 blot based on 3 independent replicates.",
    "ncbi_link": "FLAG: 
NRPB2: 828259"
  },
  {
    "caption": "Transmission rate of nrpb2-2 allele in nrpb2-2 +/- line (n=197) and nrpb2- +/- lines combined with homozygous NRPB2P979S-FLAG +/+ (n=280), NRPB2Y732F-FLAG +/+ (n=240) and NRPB2WT-FLAG +/+ (n=210), respectively. Fisher´s exact test was used as a statistic test, three asterisks denote p<0.001 between samples and n.s. stands for not significant.",
    "ncbi_link": "FLAG: 
nrpb2: 828259
NRPB2: 828259"
  },
  {
    "caption": "Image of homozygous mutant nrpb2-2 fully complemented by NRPB2WT-FLAG (top, NRPB2WT +/+ nrpb2-2 -/-) and partially complemented by NRPB2Y732F-FLAG (bottom, NRPB2WT +/+ nrpb2-2 -/-). Plants were grown for 4 weeks in soil. Scale bars represent 1 cm.",
    "ncbi_link": "FLAG: 
NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Schematic drawing of the experimental design to investigate RNAPII transcription speed in vivo. In brief, Arabidopsis seedlings of NRPB2WT-FLAG Col-0 and NRPB2Y732F-FLAG Col-0 were grown on MS media for 12 days and then were transferred to MS liquid media for 2 days. Flagellin peptides (flagellin 22) were added into media and treated samples were collected in a 0 minute (no treatment), 2 minutes and 4 minutes time course. The nascent RNA was isolated and used for reverse transcription and qPCR analyses to reveal RNAPII accumulation at different region in genes. See Methods for technical details.",
    "ncbi_link": "FLAG: 
NRPB2: 828259"
  },
  {
    "caption": "Nascent RNA profile of AT5G41750. Nascent RNA RT-qPCR assay measuring RNAPII signal at 3 positions (dark red bars: probe 1, 2 and 3) on the gene upon flagellin 22 treatment in a 0 minute, 2 minutes, 3 minutes and 4 minutes time course. Nascent RNA signal values were normalized to reference gene ACT2. Error bars represent SEM from 3 independent replicates. The statistical significance of differences between NRPB2Y732F and NRPB2WT at the same time point were assessed by the two-sided Student's t-test. n.s. denotes not significant; * denotes p<0.05 and ** denotes p<0.01. Scale bar (black) represent 0.5 kb.",
    "ncbi_link": "ACT2: 
AT5G41750: 834178
NRPB2: 828259"
  },
  {
    "caption": "Nascent RNA profile of AT4G19520. Nascent RNA RT-qPCR assay measuring RNAPII signal at 3 positions (dark red bars: probe 1, 2 and 3) on the gene upon flagellin 22 treatment in a 0 minute, 2 minutes, 3 minutes and 4 minutes time course. Nascent RNA signal values were normalized to reference gene ACT2. Error bars represent SEM from 3 independent replicates. The statistical significance of differences between NRPB2Y732F and NRPB2WT at the same time point were assessed by a two-sided Student's t-test. n.s. denotes not significant; * denotes p<0.05 and ** denotes p<0.01. Scale bar (black) represents 0.5 kb.",
    "ncbi_link": "ACT2: 
AT4G19520: 827694
NRPB2: 828259"
  },
  {
    "caption": "plaNET-seq signal of RNAPII in the promoter proximal region of AT1G70600 in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Arrows indicate the RNAPII signal at the region of promoter-proximal stalling.",
    "ncbi_link": "AT1G70600: 843397
NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Metagene profile of plaNET-seq mean signal of RNAPII in a 1 Kb window centered at the +1 nucleosome in Arabidopsis genes (n=25474) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). The significance of differences of plaNET-seq signal in the region from -25 bins to +25 bins around +1 nucleosome between NRPB2WT and NRPB2Y732F were assessed by a two-sided Mann-Whitney U-test, p=5.20e-10.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "RNAPII stalling index calculated for all the genes with plaNET-Seq FPKM ≥ 10 in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red) (n=6596). Medians of the stalling index are 1.891 and 1.222 for NRPB2WT and NRPB2Y732F, respectively. *** denotes p-value <0.001 by Wilcoxon signed-rank test. The solid horizontal lines and box limits represent medians, lower and upper quartiles of data values in each group. The upper and lower whiskers extend to the largest or smallest value, respectively, no further than 1.5 * IQR from the relevant quartile.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Metagene profile of plaNET-seq mean signal over whole genes (length from 0.5 Kb to 5 Kb, scaled to 500 bins, n=27042) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red).",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Metagene profile of plaNET-seq mean signal of RNAPII in exons (length from 50 bp to 300 bp, scaled to 100 bins, n=73925) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Pink dashed line rectangle illustrates the amplitude of differences between the minimum and the maximum of RNAPII signal across the exons. A two-sided Mann-Whitney U-test was used to assess the plaNET-seq signal of NRPB2WT (blue) and NRPB2Y732F (red) in exons, p<1e-16. Metagene profile of plaNET-seq mean signal of RNAPII in introns (50 bp to 300 bp, scaled to 100 bins, n=102260) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). A two-sided Mann-Whitney U-test was used to assess the plaNET-seq signal of NRPB2WT (blue) and NRPB2Y732F (red) in introns, p<1e-16.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Bar charts showing the fractions of 3' and 5' splicing intermediate reads from plaNET-seq in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red).",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Genome browser snapshots illustrating enhanced intron splicing in NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F, red) compared to NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT ,blue). Scale bars denote 0.5 Kb.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "The fraction of RNA-seq intronic reads calculated for all genes (n=24912) in NRPB2WT +/+ nrpb2-2 -/- and NRPB2Y732F +/+ nrpb2-2 -/-. Two-sided Mann-Whitney U test: **** denotes p-value<2.2e-16. The solid horizontal lines and box limits represent medians, lower and upper quartiles of data values in each group. The upper and lower whiskers extend to the largest or smallest value, respectively, no further than 1.5 * IQR from the relevant quartile.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Differentially expressed (DE) exons and introns in NRPB2Y732F +/+ nrpb2-2 -/- compared to NRPB2WT +/+ nrpb2-2 -/- based on RNA-seq results. Numbers of DE exons and introns were shown in plot. Quantification (log fold change of FPKM from RNA-seq) of differentially expressed (DE) exons and non-DE exons in NRPB2Y732F +/+ nrpb2-2 -/- compared to NRPB2WT +/+ nrpb2-2 -/-. ** denotes p-value <0.01 by Wilcoxon signed-rank test. The solid horizontal lines and box limits represent medians, lower and upper quartiles of data values in each group. The upper and lower whiskers extend to the largest or smallest value, respectively, no further than 1.5 * IQR from the relevant quartile.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Genome browser snapshots illustrating enhanced exon skipping in NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F, red) compared to NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT ,blue). Scale bars denote 0.5 Kb. Quantification (log fold change of FPKM from RNA-seq) of differentially expressed (DE) introns and non-DE exons in NRPB2Y732F +/+ nrpb2-2 -/- compared to NRPB2WT +/+ nrpb2-2 -/-. **** denotes p-value <0.0001 by Wilcoxon signed-rank test. The solid horizontal lines and box limits represent medians, lower and upper quartiles of data values in each group. The upper and lower whiskers extend to the largest or smallest value, respectively, no further than 1.5 * IQR from the relevant quartile.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "plaNET-seq signal of RNAPII at 3' end of AT2G21410 in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Arrows indicate the RNAPII signal peaks at PAS stalling region.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259
AT2G21410: 816680"
  },
  {
    "caption": "Metagene profile of plaNET-seq mean signal of RNAPII in a 1 kb window centered at PAS (n=24448) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). The significance of differences of plaNET-seq signal in the region from PAS to +100 bins between NRPB2WT and NRPB2Y732F were assessed by Two-sided Mann-Whitney U-test, p = 1.53e-06.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Histogram of transcriptional read-through length (nt) from PAS of protein-coding gene (plaNET-seq FPKM>5, n=9316) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red).",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Box plot shows the RNAPII transcriptional read-through length from PAS of protein-coding genes (plaNET-seq FPKM>5 n=9316) called based on statistic model (see Methods) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Median of read-through length in NRPB2WT and NRPB2Y732F mutant are 534 nt and 649 nt. Two-sided Mann-Whitney U-test: *** denotes p = 9.9e-62. The solid horizontal lines and box limits represent medians, lower and upper quartiles of data values in each group. The upper and lower whiskers extend to the largest or smallest value, respectively, no further than 1.5 * IQR from the relevant quartile.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "Metagene plot of RNAPII signal by plaNET-seq anchored at both PAS of upstream genes and TSS of downstream genes for tandemly oriented genes (n=5753) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Red arrow denotes the direction of transcriptional read-through. Pink dashed line rectangle indicates the region corresponding to the second half of PAS-TSS gaps along 5' to 3' direction. Metagene plot of RNAPII signal by plaNET-seq anchored at PASs of both upstream genes and downstream genes for gene pairs located in \"tail to tail\" orientation (n=1384) in NRPB2WT +/+ nrpb2-2 -/- (NRPB2WT, blue) and NRPB2Y732F +/+ nrpb2-2 -/- (NRPB2Y732F ,red). Red arrows denote the directions of transcriptional read-through from both PASs. Pink dashed line rectangles indicate the region corresponding to the second half of PAS-TSS gaps along 5' to 3' direction.",
    "ncbi_link": "NRPB2: 828259
nrpb2: 828259"
  },
  {
    "caption": "B. MASTL  was ablated in MDA-MB-231  cells using the isgMASTL system. 72 h after Dox, cells were starved  of glucose  in the media in presence of 10% dFBS for 1 h (-) and then  re-stimulated with 25 mM of glucose  for 10 min before recovery (+). Whole-cell lysates were blotted  with the indicated antibodies. * in indicates unspecific band. β-Actin  was used as a loading control.",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "C. MASTL  was depleted in MDA-MB-231 cells using shRNAs against MASTL  (+) or scrambled shRNAs (−) as control. Cells were starved  from glucose  for 2 h and re-stimulated  with 5 mM glucose  for 15 min and 1 h. Total extracts were recovered and tested for the indicated antibodies. β-Actin was used as a loading control. D. Quantification of phospho-AKT  T308 levels in glucose deprivation  or glucose stimulation  (15 min) conditions in MDA-MB-231 control cells and MASTL-depleted cells either using shRNA or the inducible sgRNA. Bars displays mean data + SEM from three independent experiments. Significance determined by Student's t-test comparing feedback activation in MASTL-depleted cells versus control cells (ns, not significant; *P<0.05).",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "E. Immunoblot  analysis with the indicated antibodies in BT-549  cells upon glucose deprivation  and 15 min glucose stimulation. MASTL  knockdown was performed by infection with a shRNA for MASTL  (+) or a Scramble shRNA (−) as a control.  β-Actin was used as a loading control. Bar chart displays mean data + SEM from 3 experiments. Significance determined by Student's t-test comparing feedback activation in MASTL-depleted cells versus control cells (ns, not significant). F. Immunoblot  analysis with the indicated antibodies in MCF-7 cells upon glucose deprivation  and glucose stimulation  for 15 min. MASTL  knockdown was performed by infection with a shRNA for MASTL  (+) or a Scramble shRNA (−) as a control. Bar chart displays mean data + SEM from 3 experiments. Significance determined by Student's t-test comparing feedback activation in MASTL-depleted cells versus control cells (ns, not significant; *P<0.05).",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "A. Time course  experiment at the indicated  time points  after 100 nM insulin  stimulation in 6 h serum-starved  control and MASTL  knockout MDA-MB-231 cells using the isgMASTL system. The plot shows the quantification of phospho-AKT  T308 after 30 min of insulin stimulation. Plots displays mean data + SEM from 5 independent experiments. *P<0.05, Student's t-test.",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "B. TSC2  was knocked down in control or MASTL-null MDA-MB-231 cells using specific (+) or Scrambled (−) shRNAs. Cells were starved for glucose  for 1 h. The plot shows the quantification of phospho-AKT  T308. Data are mean + SEM from 3 independent experiments. ns, not significant; *P<0.05, 1-way ANOVA.",
    "ncbi_link": "MASTL: 84930
TSC2: 7249"
  },
  {
    "caption": "C. MDA-MB-231  control (−) or MASTL  null (+) cells were treated with 100 nM rapamycin  or vehicle as control. Cells were starved  for glucose  for 1 h and  re-stimulated  with glucose  for 15 min; rapamycin  was added 15 min before glucose stimulation. The plot shows the quantification of phospho-AKT  T308. Data are mean + SEM from 3 independent experiments. ns, not significant; *P<0.05, 1-way ANOVA.",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "E. GLUT4 staining  (magenta) in skeletal muscle sections. Vinculin  (membrane) and DAPI  (DNA) staining  is shown in yellow and cyan, respectively. Scale bars, 50 µm. Mice  were fasted  overnight for 16 h, and  re-fed  for 2 h before sample collection. Quantification of the mean intensity [relative units x103; n=3 Mastl(+/+) and 3 Mastl(∆/∆)] is shown. Data points reflect the mean + SEM; *P<0.05; ***P <0.001; unpaired Student's t-test.",
    "ncbi_link": "Mastl: 67121"
  },
  {
    "caption": "G. Immunoblot  with the indicated antibodies in liver  tissues from Mastl(+/+) (n=6) and Mastl(Δ/Δ) (n=7) mice. Mice  were fasted overnight for 16 h, injected intraperitoneally with glucose  (2 g/kg body), and sacrificed 30 min later for sample collection. Quantification of the relative fold change signal of phospho-AKT  T308 (normalized to total AKT  level). n=6 Mastl(+/+) and 7 Mastl(Δ/Δ) mice. Charts reflect the mean + SEM; *P<0.05; unpaired Student's t-test.",
    "ncbi_link": "Mastl: 67121"
  },
  {
    "caption": "A. Co-depletion of ENSA and ARPP19  proteins in the MDA-MB-231 cell line using specific siRNAs or control siRNAs against luciferase  (Luc). 72 h after transfection cells were starved  for glucose  for 1 h and re-stimulated  with glucose  for 15 min. Total cell extracts were collected and analyzed for the indicated antibodies.",
    "ncbi_link": "Luc: 
luciferase: 
ARPP19: 10776
ENSA: 2029"
  },
  {
    "caption": "B. isgMASTL  cells were previously infected with lentiviral  supernatants expressing FLAG- and HA-tagged versions of ENSA  and ARPP19  phospho-mimetic mutants (S67D and S62D) or GFP  as a control. Cells were treated with Dox  to induce MASTL CRISPR/Cas9-dependent knock-out, and 72 h later cells were treated as specified in A. The plot displays mean + SEM from 3 independent experiments. Significance determined by Student's t-test comparing ENSA/ARPP19  overexpression versus control cells (ns, not significant; *P<0.05).",
    "ncbi_link": "CRISPR: 
FLAG: 
GFP: 
HA: 
ARPP19: 10776
Cas9: 69900935
ENSA: 2029
MASTL: 84930"
  },
  {
    "caption": "C. Control (Dox  −) and MASTL  knockout (Dox  +) cells were treated with 5 µM fostriecin, 50 nM  okadaic acid (OA) or vehicle (Veh) 10 min before insulin  stimulation for 30 min. Total lysates were analyzed for the indicated antibodies and P-T308-AKT  signal was quantified. β-Actin was used as a loading control. The plot represents mean + SEM from 3 independent experiments, except for fostriecin  treatment in which only data from two experiments were obtained and no error bars are shown. *P<0.05; Student's t-test.",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "A. MDA-MB-231 cells were co-transduced with specific siRNAs against the PPP2R2A  (B55α) and PPP2R2D  (B55δ) transcripts (B55αδ) or against luciferase  (Luc) as a control. Asynchronous cells were collected and blotted  for the indicated antibodies. The histograms represent the quantifications of the specified phospho-residues. Plots show mean + SEM from 3 independent experiments. *P<0.05, Student's t-test.",
    "ncbi_link": "Luc: 
luciferase: 
PPP2R2A: 5520
B55α: 5520
PPP2R2D: 55844
B55δ: 55844"
  },
  {
    "caption": "B. Immunodetection  of the indicated antigens in control (−) and MASTL  knockout (+) cells starved  from glucose  and re-stimulated with glucose  for 15 min.",
    "ncbi_link": "MASTL: 84930"
  },
  {
    "caption": "C. siRNA-mediated genetic depletion of B55alpha  and delta subunits (B55αδ) in control (Dox  −) and MASTL-null (Dox  +) cells. The phosphorylation  status of the different proteins was scored in conditions of glucose  re-addition. n=3 independent experiments. The plot shows mean + SEM from 3 independent experiments. *P<0.05, 1-way ANOVA.",
    "ncbi_link": "MASTL: 84930
B55alpha: 5520
B55α: 5520"
  },
  {
    "caption": "D. Immunoblot  with the indicated antibodies in  skeletal muscle (gastrocnemius) extracts. Mice  were fasted overnight for 16 h, injected intraperitoneally with glucose  (2 g/kg body), and sacrificed 30 min later for sample collection. Quantification of the relative fold change signal of total IRS1, and phospho-S6K1  T389 (normalized to total S6K1  level; n=6 Mastl(+/+) and 7 Mastl(∆/∆)). vinculin  were used as a loading control. Data are mean + SEM; *P<0.05, unpaired Student's t-test.",
    "ncbi_link": "Mastl: 67121"
  },
  {
    "caption": "B. Cas9-expressing control (−) cells or cells with CRIPSR/Cas9-mediated TSC2  knockout (sgTSC2) were treated with rapamycin  (Rap), Torin1  (Tor), or vehicle as control (V). MASTL-knockdown cells (shMASTL) were used as an additional control of the specificity of the antibody. Inhibitors were added 15 min before glucose  re-stimulation for additional 15 min and total cell lysates were harvested for immunoblot. The plot shows the quantification of phospho-MASTL  T194 as mean from 2 independent experiments.",
    "ncbi_link": "CRIPSR: 
Cas9: 69900935
MASTL: 84930
TSC2: 7249"
  },
  {
    "caption": "G. isgMASTL MDA-MB-231 cells were transduced with the indicated Mastl  mutants or GFP  alone as a control, and treated with doxycycline  (Dox) to induce Mastl  deletion. Cells were collected after glucose  stimulation, and total lysates blotted  for the indicated antibodies.",
    "ncbi_link": "GFP: 
MASTL: 84930
Mastl: 67121"
  },
  {
    "caption": "(G) GTT or ITT in 17-week-old wild-type or JFKTG mice fed on HFD. Error bars represent mean ± SEM (n = 6, *p < 0.05, paired two-tailed Student's t-test).",
    "ncbi_link": "JFK: 54455"
  },
  {
    "caption": "(H) H&E and Oil Red O staining of liver sections from wild-type or JFKTG mice fed on ND or HFD. Scale bar, 100 μm.",
    "ncbi_link": "JFK: 54455"
  },
  {
    "caption": "(D) The body weight of male wild-type or JfkKO mice fed on HFD. Error bars represent mean ± SEM (n = 6, *p < 0.05, paired two-tailed Student's t-test).",
    "ncbi_link": "Jfk: 54455"
  },
  {
    "caption": "(G) H&E and Oil Red O staining of liver sections from wild-type or JfkKO mice fed on HFD. Scale bar, 100 μm.",
    "ncbi_link": "Jfk: 54455"
  },
  {
    "caption": "(H) Wild-type or JfkKO mice were fed with HFD for 11 weeks prior to injection of adenovirally-delivered vector or JFK via tail vein. Seven days after injection, total proteins prepared from liver tissues were subjected to western blotting analysis for the expression of Jfk or measurement for hepatic TG and NEFA content. Error bars represent mean ± SEM (n = 6, *p < 0.05, one-way ANOVA with Tukey's HSD test). H&E and Oil Red O staining of liver sections are shown. Scale bar, 100 μm.",
    "ncbi_link": "Jfk: 54455
JFK: 54455"
  },
  {
    "caption": "(A) HepG2 cells were stably transfected with vector or FLAG-JFK. Cellular extracts were immunopurified with anti-FLAG immunoaffinity resin and eluted with FLAG peptides. The eluates were resolved on SDS-PAGE and silver-stained. The proteins bands were retrieved and analyzed by mass spectrometry.",
    "ncbi_link": "FLAG: 
JFK: 54455"
  },
  {
    "caption": "(E) HepG2 cells were transfected with FLAG-JFK and treated with 50 μg/ml CHX for the indicated times in the presence or absence of MG132 for western blotting analysis. Quantitation was done by densitometry and expressed as signals of ING5/β-actin.",
    "ncbi_link": "FLAG: 
JFK: 54455"
  },
  {
    "caption": "(C) HepG2 cells were treated with control siRNAs or siRNAs against JFK or/and ING5, or transfected with vector, JFK, or/and ING5. Cellular extracts were prepared for western blotting analysis with the indicated antibodies.",
    "ncbi_link": "JFK: 54455
ING5: 84289"
  },
  {
    "caption": "(D) HepG2 cells were transfected with vector or JFK, AMPKα1, or/and ING5, or treated with control siRNAs or siRNAs against JFK, AMPKα1, or/and ING5, Cellular extracts were prepared for AMPK activity assays by ELISA. Error bars represent mean ± SD for triplicate experiments (*p < 0.05, paired two-tailed Student's t-test).",
    "ncbi_link": "JFK: 54455
ING5: 84289
AMPKα1: 5562"
  },
  {
    "caption": "(D) The measurement of AMPK activity and the rate of fatty acid β-oxidation of wild-type or JfkKO mice. Cellular extracts prepared from MEFs or liver tissues were subjected to AMPK activity assays by ELISA. Mitochondria were isolated from MEFs or liver tissues, and the rate of fatty acid β-oxidation was quantified by spectrophotometric detection for ferricyanide-trapped reduced products. Error bars represent mean ± SEM (n = 6, *p < 0.05, paired two-tailed Student's t-test).",
    "ncbi_link": "Jfk: 54455"
  },
  {
    "caption": "Wild-type or JfkKO mice were fed with HFD for 11 weeks prior to injection of adenovirally-delivered vector control, shIng5, or shAmpkα1 via tail vein. Seven days after injection, cellular extracts prepared from liver tissues were subjected to western blotting analysis or measurement for hepatic TG and NEFA content (E). Asterisk (*) represents significant comparison to wild-type mice, octothorpe (#) represents significant comparison to JfkKO mice. Error bars represent mean ± SEM (n = 6, *p < 0.05, #p < 0.05, one-way ANOVA with Tukey's HSD test).",
    "ncbi_link": "Jfk: 54455
Ing5: 66262
Ampkα1: 105787"
  },
  {
    "caption": "B. Characteristics of 96 patients with an EGFR-activating mutation who were treated with EGFR-TKI. Each column corresponds to one patient. Data include general characteristics (stage at diagnosis, age, sex, tobacco usage, position of EGFR mutation, TKI type), progression-free survival (PFS; lower graph) and intensity of RHOB staining as determined by immunohistochemistry (null: 0, weak: +, moderate: ++ and high: +++).",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "C. Representative scans of patients with low or high RHOB-expressing lung tumors, before and after erlotinib treatment. Red arrows indicate lung tumors.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "D. Progression-free survival of erlotinib-treated patients with EGFR-mutated lung tumors, according to RHOB expression, assessed by immunohistochemistry (low RHOB group = negative + weak staining; high RHOB group = moderate + high staining).",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "G. RHOB immunostaining score evolution in EGFR-mutated lung tumors before treatment and after EGFR-TKI relapse.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "A. Representative H&E staining of whole lungs from EGFRL858R/Rhob-/-, EGFRL858R/Rhob+/- and EGFRL858R/Rhob+/+ mice treated or not with erlotinib (12.5 mg/kg/day) for four days. Scale bar: 5 mm. B. Quantification of the tumor/lung ratio. n=7 for each group except for EGFRL858R/Rhob+/- placebo (n=6).",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "C. Representative Ki67 immunostaining of EGFRL858R/Rhob-/-, EGFRL858R/Rhob+/- and EGFRL858R/Rhob+/+ mice treated or not with erlotinib (12.5 mg/kg/day) for four days (scale bar: 50 µm), and the corresponding quantification (D). Three independent zones/mice lung were used for quantification. n=21 (7 mice) for each group except for EGFRL858R/Rhob+/- placebo (n=18; 6 mice).",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "E. Immunostaining of cleaved caspase-3 in lung tumors from EGFRL858R/Rhob+/+ or EGFRL858R/Rhob-/- mice treated for 24 h with erlotinib at 12.5 mg/kg. Scale bar: 50 µm. (**: p<0.001 vs. placebo; ***: p<0.0001 vs. placebo).",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "HCC4006 cells were (A) transfected with two siRNA against RHOB (siB1, siB2) then treated with increasing doses of erlotinib. The surviving cell fraction was determined by an MTS assay after 72 h and compared to untreated cells.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "HCC4006 cells were (A) transfected with two siRNA against RHOB (siB1, siB2). RHOB overexpression was monitored by western blotting. (***: p<0.0001 vs. control cells). Data are representative of at least three independent experiments.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "HCC4006 cells were (B) transduced with control (AdCont) or RHOB-overexpressing adenoviruses (AdRHOB) then treated with increasing doses of erlotinib. The surviving cell fraction was determined by an MTS assay after 72 h and compared to untreated cells.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "HCC4006 cells were (B) transduced with control (AdCont) or RHOB-overexpressing adenoviruses (AdRHOB). RHOB overexpression was monitored by western blotting. (***: p<0.0001 vs. control cells). Data are representative of at least three independent experiments.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "Erlotinib IC50 values were quantified in RHOB-overexpressing or RHOB-depleted (D) HCC827 cells, (E) HCC2935 cells and (F) H3255 cells, as determined by an MTS assay after 72 h treatment. RHOB overexpression or inhibition was monitored by western blotting for each condition.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "G. HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing adenoviruses (AdRHOB) at an increasing multiplicity of infection (MOI), then erlotinib IC50 values were determined after 72 h by an MTS assay and a correlation analysis was performed.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "G. HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing adenoviruses (AdRHOB) at an increasing multiplicity of infection (MOI). RHOB overexpression was monitored by western blotting. (***: p<0.0001 vs. control cells). Data are representative of at least three independent experiments.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "A. HCC4006, HCC827, HCC2935 and H3255 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for four hours with erlotinib at concentrations corresponding to the respective IC50 values determined for each control cell line. The phosphorylation status of AKT, ERK1/2 and EGFR was assessed by western blotting and normalized according to total protein levels. RHOB overexpression was also monitored by western blotting.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "B. Representative immunostaining of phospho-AKT (Ser473), phospho ERK1/2 and their total protein amounts in lung tumors from EGFRL858R/Rhob-/- or EGFRL858R/Rhob+/+ mice treated or not with erlotinib (12.5 mg/kg/day) for four days. The remaining hyperplastic areas were selected in erlotinib-treated mice to efficiently characterize the effect of erlotinib on ERK and AKT pathways in both Rhob genotypes. Scale bar: 100 µm.",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "C. HCC4006 cells were transfected with a plasmid coding for a constitutively active AKT mutant (AKTmyr, myristoylated) or an empty vector (ø), and treated for 72 h with increasing concentrations of erlotinib. The surviving cell fraction was determined by an MTS assay. Data are representative of at least three independent experiments.",
    "ncbi_link": "AKT: 10000///208///207"
  },
  {
    "caption": "C. HCC4006 cells were transfected with a plasmid coding for a constitutively active AKT mutant (AKTmyr, myristoylated) or an empty vector (ø), and treated for 72 h with increasing concentrations of erlotinib. AKT overexpression and phosphorylation at Ser473 were assessed by western blotting. Data are representative of at least three independent experiments.",
    "ncbi_link": "AKT: 10000///208///207"
  },
  {
    "caption": "A. HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for four hours with erlotinib (100 nM), G594 (100 nM), or a combination of both drugs. The phosphorylation status of GSK3β (Ser9), ERK1/2 and EGFR (Tyr1173) was assessed by western blotting and normalized according to the total protein levels. RHOB overexpression was also monitored by western blotting.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "B. HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for 72 h with erlotinib alone (black and red curves) or in combination with the AKT inhibitor G594 at 100 nM (green and blue curves). The surviving cell fraction was determined by an MTS assay.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "C. HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing adenoviruses (AdRHOB) and treated for 72 h with increasing concentrations of erlotinib in the absence or presence of increasing doses of G594. The surviving cell fraction was determined by an MTS assay, and erlotinib IC50 values were determined for each condition. (**: p<0.001 vs. AdCont cells; ***: p<0.0001 vs. AdCont cells). HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for 48 h with erlotinib (100 nM), G594 (100 nM), or a combination of both drugs.",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for 48 h with erlotinib (100 nM), G594 (100 nM), or a combination of both drugs. Apoptosis was then determined by quantification of the subG1 cell population (D).",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "HCC4006 cells were transduced with control (AdCont) or RHOB-overexpressing (AdRHOB) adenoviruses and treated for 48 h with erlotinib (100 nM), G594 (100 nM), or a combination of both drugs. Apoptosis was then determined by detection of cleaved PARP and caspase-3 (E).",
    "ncbi_link": "RHOB: 388"
  },
  {
    "caption": "A. Representative H&E staining of lung tumors from EGFRL858R/Rhob-/-, EGFRL858R/Rhob+/- and EGFRL858R/Rhob+/+ mice treated or not during four days with erlotinib (12.5 mg/kg/day), with the AKT inhibitor G594 (25 mg/kg/day), or in combination with both drugs. Scale bar: 500 µm. B. Quantification of the tumor/lung ratio of mice treated or not with the individual drugs or with a combination of both.",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "C. Representative Ki67 immunostaining of lung tumors from EGFRL858R/Rhob-/-, EGFRL858R/Rhob+/- and EGFRL858R/Rhob+/+ mice treated or not with erlotinib alone (12.5 mg/kg/day) or in combination with the AKT inhibitor G594 (25 mg/kg/day) for four days (scale bar: 50 µm), and the corresponding quantification (D).",
    "ncbi_link": "EGFR: 13649
Rhob: 11852"
  },
  {
    "caption": "(B) Full-length or truncated versions of ATG16L1 were subjected to an in vitro ULK1 kinase assay. ULK1 and ATG16L1 inputs were examined by western blot and target phosphorylation by autoradiography. Data information: Unless otherwise indicated experiments were performed three times.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(D) Full-length or mutated HA-ATG16L1 was purified from mammalian cells and subjected to an in vitro ULK1 kinase assay. Inputs were analysed by WB and target phosphorylation by AR. Data information: Unless otherwise indicated experiments were performed three times.",
    "ncbi_link": "HA: 
ATG16L1: 55054"
  },
  {
    "caption": "(E) HEK293A cells were transfected with wild-type or phospho-dead ATG16L1 in the presence of wild-type or kinase-dead ULK1. Phosphorylation of ATG16L1 (S278 or S287) and inputs were examined by WB. Data information: Unless otherwise indicated experiments were performed three times.",
    "ncbi_link": "ATG16L1: 55054
ULK1: 8408"
  },
  {
    "caption": "(A) Wild-type, ULK1/2 double knockout (dKO), or IKKα KO mouse embryonic fibroblasts (MEFs) were incubated with either complete medium, amino acid-deficient DMEM, or HBSS for 1 hour. Samples were immunoblotted using the indicated antibodies. Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "IKKα: 12675
ULK1: 22241"
  },
  {
    "caption": "(B) Wild-type, ULK1/2 dKO, or IKKα KO MEFs were infected with log phase Salmonella for 2 hours; bacteria-containing media was then removed and cells were incubated with gentamycin (50 µg/mL)-containing DMEM for 2 hours. Samples were immunoblotted using the indicated antibodies. Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "IKKα: 12675
ULK1: 22241"
  },
  {
    "caption": "(C) Wild-type, ULK1/2 dKO, or IKKα KO MEFs cells were infected with Salmonella for 1 hours. Autophagic capture of Salmonella was analyzed by immunostaining for LPS and LC3B. Representative images are shown (scale bars, 10 μm and 3 μm). Quantification was generated from 8 fields of view from a representative experiment. The experiments were repeated twice. Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "IKKα: 12675
ULK1: 22241"
  },
  {
    "caption": "(D) Wild-type, ULK1/2 dKO and IKKα KO MEFs were infected with Salmonella for 1 hour. Xenophagy rates were examined through Colony Forming Unit (CFU) assays. Quantification of infection rates by immunofluorescence is demonstrated in the right panel. Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "IKKα: 12675
ULK1: 22241"
  },
  {
    "caption": "(A) HEK293A cells were transfected with either flag-tagged WT ATG16L1 or T300A ATG16L1. ULK1 was co-transfected in increasing amounts where indicated. Cleavage of ATG16L1 was analyzed by WB of whole cell lysates. Levels of ATG16L1 cleavage were quantified from 3 biological repeats (right panel). Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "flag: 
ATG16L1: 55054
ULK1: 8408"
  },
  {
    "caption": "(B) HEK293A cells were transfected with either tagged wild-type, T300A, or S278/T300A ATG16L1 in the presence or absence of ULK1. Cleavage of ATG16L1 was analyzed by WB. Levels of ATG16L1 cleavage were measured from 3 biological repeats (right panel). Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "ATG16L1: 55054
ULK1: 8408"
  },
  {
    "caption": "(E) ATG16L1 knock-out HEK293A cells transfected with the indicated HA GST ATG16L1 plasmids were infected with Salmonella for 1 hour. Xenophagy rates were examined through CFU assays. Quantification of infection rates by immunofluorescence is demonstrated in the right panel. Data information: Unless otherwise indicated experiments were performed three times. Data are represented as mean ± standard deviation and p values were determined by Student's T-Test.",
    "ncbi_link": "GST: 
HA: 
ATG16L1: 55054"
  },
  {
    "caption": "(B) Wild-type and ULK1/2 dKO were infected with Salmonella for 25 minutes. Immunofluorescence was performed using antibodies against LPS and ATG16L1. Representative immunofluorescent images are shown on the left panel (scale bars, 10 μm and 2 μm). Quantification of ATG16L1-positive bacteria from 7 fields of view from a representative experiment is shown in the right panel. Data information: Unless otherwise indicated experiments were performed twice. Data are represented as mean and p values were determined by Student's T-Test.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "(C) ATG16L1 knock-out HCT116 transfected with the indicated GST HA ATG16L1 were infected with Salmonella for 1 hour. Bacteria were stained using anti-LPS antibodies to analyze localization in addition to ATG16L1. Representative immunofluorescent images of ATG16L1 and LPS are shown (scale bars, 5μm and 1 μm). Quantification of ATG16L1 localizing to bacteria from 7 fields of view from a representative experiment is shown in the lower panel. Data information: Unless otherwise indicated experiments were performed twice. Data are represented as mean and p values were determined by Student's T-Test.",
    "ncbi_link": "GST: 
HA: 
ATG16L1: 55054"
  },
  {
    "caption": "(D) ATG16L1 knock-out HCT116 transfected with the indicated GST HA ATG16L1 were infected with Salmonella for 1 hour. Bacteria were stained using anti-LPS antibodies to analyze localization in addition to the autophagy marker LC3B. Representative immunofluorescent images of LC3B and LPS are shown (scale bars, 5μm and 1 μm). Quantification of bacteria undergoing autophagic clearance from 7 fields of view from a representative experiment is shown in the lower panel. Data information: Unless otherwise indicated experiments were performed twice. Data are represented as mean and p values were determined by Student's T-Test.",
    "ncbi_link": "GST: 
HA: 
ATG16L1: 55054"
  },
  {
    "caption": "(A) Autophagic markers from mixed midbrain gba+/+, gba+/−, and gba−/− cultures were analyzed via western blotting using antibodies as indicated.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(B) Autophagic flux was analyzed in gba+/+ and gba−/− midbrain neurons. Neurons were treated with 100 nM bafilomycin A1 and 1 μM rapamycin and flux assayed by comparing LC3I and LC3II levels via western blotting. β-actin was used as a loading control.(C) Densitometry analyzes of autophagy of (B) expressed as a ratio of LC3II/LC3I. Error bars, ± SEM. *p < 0.05.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(G) Proteasomal activity (chymotrypsin activity) was measured using the Proteasome Glo assay where activity is proportional to the released luciferase. RFU, relative luciferase units. Data represent the mean ± SEM (n = 3, each experiment contained triplicates for each genotype). *p < 0.05.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(A) Levels of soluble and insoluble α-synuclein from midbrain of P1 gba+/+ and gba−/− mice. TX-100 soluble and insoluble (SDS/Urea) factions were isolated and analyzed via western blotting with α-synuclein antibodies. β-actin was used as a loading control.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(B) Sagittal brain stem sections from gba+/+, gba+/−, and gba−/− mice were stained with α-synuclein antibodies. Scale bar, 1,000 μm.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(A) Neurons and astrocytes from gba+/+, gba+/−, and gba−/− mice were stained with TMRM. The mean florescence intensity in mitochondria was analyzed via confocal microscopy (n = 3, >32 cells analyzed/experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(B) Neurons from gba+/+ and gba−/− bathed in TMRM containing recording solution and fluorescence intensity analyzed via confocal microscopy. After 1 min, 1 μM oligomycin was added followed by 1 μM FCCP (n = 5, three cells analyzed/experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(C) Neurons from gba+/+ and gba−/− incubated with 5 mM methyl pyruvate 5 min prior to imaging. Cells bathed in 25 nM TMRM and 5 mM methyl pyruvate containing recording solution and fluorescence intensity analyzed via confocal microscopy. After 90 s, 1 μM oligomycin was added, followed by 1 μM FCCP (n = 3, three cells analyzed/experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(D) As in (C), except cells were bathed in 10 mM methyl succinate, (n = 3, four cells/experiment). All data in this figure represent the mean ± SEM, *p < 0.05. Neurons from gba+/+ and gba−/− incubated with 5 mM methyl pyruvate 5 min prior to imaging. Cells bathed in 25 nM TMRM and 5 mM methyl pyruvate containing recording solution and fluorescence intensity analyzed via confocal microscopy. After 90 s, 1 μM oligomycin was added, followed by 1 μM FCCP (n = 3, three cells analyzed/experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(A) Oxygen consumption rates of gba+/+, gba+/−, and gba−/− mixed midbrain cultures. Basal oxygen consumption was measured over 3 min. The maximal (uncoupled) rate was measured via the addition of FCCP and the nonmitochondrial oxygen consumption analyzed via the addition of antimycin A (n = 3, three runs/experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(B) Complex I-NADH: Ubiquinone reductase activity from gba+/+, gba+/−, and gba−/− brains expressed as a ratio to citrate synthase (n = 3).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(C) Complex II-III: Succinate dehydeogenase, cytochome c reductase activity from gba+/+, gba+/−, and gba−/− brains expressed as a ratio to citrate synthase (n = 3).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(D) Complex IV activity from gba+/+, gba+/−, and gba−/− brains expressed as a ratio to citrate synthase (n = 3).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(F) gba+/+and gba−/− cells treated with 3 nM decylTPP and MitoQ10 for 48 hr were subjected to immunoblotting using the indicted antibodies. All data in this figure represent the mean ± SEM, *p < 0.05.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(C) Levels of morphology proteins from gba+/+, gba+/−, and gba−/− isolated mitochondria were analyzed via immunoblotting with the indicated antibodies.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(D) Midbrain gba+/+, gba+/−, and gba−/− astrocytes expressing GFP-DRP1K38A were immunostained for cytochrome c and mitochondrial morphologies analyzed; concurrently cells were stained with TMRM and fluorescence intensity analyzed via confocal microscopy. Scale bar, 20 μm (n = 3, >15 cells/experiment). All data in this figure represent the mean ± SEM.",
    "ncbi_link": "DRP1: 74006
gba: 14466"
  },
  {
    "caption": "(B) Midbrain gba+/+ and gba−/− neurons and astrocytes were transfected with YFP-Parkin. Half the transfected cells were treated for 1 hr with 10 μM FCCP and all bathed in TMRM containing recording solution and imaged using confocal microscopy. Scale bar, 20 μm.(C) TMRM fluorescence intensity of cells from (B) was analyzed via confocal microscopy. Data represent the mean ± SEM, (n = 3, >4 cells analyzed per experiment).",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "(D) Mitochondria within midbrain neurons were uncoupled by the addition of 10 μM FCCP for 1 and 6 hr. PINK1 expression analyzed via immunoblotting on isolated mitochondria from gba+/+ and gba−/− neurons. Mitochondrial CI subunit NDUFS4 was used as a loading control.",
    "ncbi_link": "gba: 14466"
  },
  {
    "caption": "C), the percentage of  pups gathered in the nest location is significantly reduced in Shank2-/- mice. Mann-Whitney test, ***P<0.001. Data information: All data are presented as mean ± SEM.",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "(H) Shank2+/+ and Shank2-/- mice displayed a significant preference for the novel object versus the familiar one in the test session, two-way mixed ANOVA, effect of object: ***P<0.001, effect of genotype: P=0.167, object x genotype interaction: P=0.667, Shank2+/+ n = 9, Shank2-/- n = 9. Data information: All graphs are presented as mean ± SEM, NS: not significant.",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "(J) Left panel: Electron micrographs of the  posterior pituitary gland  from Shank2+/+ and Shank2-/- mice in lower (left panel) and higher magnification. Scale bar (500 nm). Right diagram: No significant difference was detected in the number of vesicles in the  posterior pituitary gland between Shank2+/+ and Shank2-/- mice, Mann-Whitney test, P=0.507, Shank2+/+ n = 3, Shank2-/- n = 3. (K-M) Additionally, Shank2-/- mice display no significant difference in: (K) Estradiol-, Mann-Whitney test, P=0.475, Shank2+/+ n = 6, Shank2-/- n = 7, (L) Progesterone, unpaired, two-tailed Student's t-test, P=0.570, Shank2+/+ n = 5, Shank2-/- n = 5 or (M) Prolactin- plasma concentrations, unpaired, two-tailed Student's t-test, P=0.980; Shank2+/+ n = 3, Shank2-/- n = 3. Data information: All data are presented as mean ± SEM, NS: not significant. E, endothelium; CL, capillary lumen; M,  mitochondria; NG, neurosecretory granule; AE, axonal endings, HYP, Hypothalamus; PIT, Pituitary gland.",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "(A-G)  qRT-PCR  analysis of mRNA expression levels  of hormonal genes and hormonal receptors normalized to house-keeping gene HMBS of 9-10 week old naive and postnatal day 1 Shank2+/+ and Shank2-/- mice: (A) Oxytocin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.335. (B) Vasopressin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.945. (C) Prolactin gene expression did not differ between Shank2+/+ and Shank2-/- mice, one-way ANOVA, P=0.202. Additionally, no significant difference was evident in (D) oxytocin receptor, one-way ANOVA, P=0.675, (E) prolactin receptor, one-way ANOVA, P=0.912, (F) vasopressin receptor, one-way ANOVA, P=0.418 and (G) estrogen receptor alpha expression, one-way ANOVA, P=0.890 in comparison to Shank2+/+ mice. All data are presented as mean ± SEM, NS: not significant. Pituitary gland, (n=3 pituitary glands pooled per value, n=3 hypothalamus (Oxytocin, Vasopressin, Oxytocin receptor, Vasopressin receptor, estrogen alpha) n=2-3 hypothalamus  (Prolactin receptor)).  HYP, hypothalamus; PIT, pituitary gland.",
    "ncbi_link": "Vasopressin: 11998
vasopressin receptor: 12000///26361///54140
Vasopressin receptor: 12000///26361///54140
estrogen alpha: 13982
estrogen receptor alpha: 13982
HMBS: 15288
Oxytocin: 18429
oxytocin receptor: 18430
Oxytocin receptor: 18430
Prolactin: 19109
prolactin receptor: 19116
Prolactin receptor: 19116
Shank2: 210274"
  },
  {
    "caption": "(E-H) Repeated pup exposure does not induce major components of social attachment behavior  in Shank2-/- females: (E) pup grooming, unpaired, two-tailed Student's t-test, ***P<0.001 (F) crouching, Mann-Whitney test, ***P<0.001 and (G) nest building, Mann-Whitney test, ***P<0.001, (H) maternal interaction, unpaired, two-tailed Student's t-test, ***P<0.001 (trial 5), Shank2+/+ n = 9, Shank2-/- n = 9. Data information: All data are presented as mean ± SEM, NS: not significant.",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "(L) Levels of synaptic proteins in the crude synaptosomes fraction (P2) from the  hypothalamus of Shank2+/+ and Shank2-/- mice. Shank2+/+ n = 5 (black bars), Shank2-/- n = 5 (blue bars). Unpaired, two-tailed Student's t-test.",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "(D-G) DREADD activation by CNO injection selectively rescues major components of social attachment behavior in Shank2-/- mice: (D) grooming, two-way ANOVA, effect of genotype: *P=0.018, effect of treatment: **P=0.002, genotype x treatment interaction: ***P=0.001. (E) Crouching, two-way ANOVA, effect of genotype: P=0.091, effect of treatment: P=0.869, genotype x treatment interaction: P=0.663, (F) nest building, two-way ANOVA, effect of genotype: P=0.415, effect of treatment: P=0.341 genotype x treatment interaction: P=0.093, (G) Maternal interaction, two-way ANOVA, effect of genotype: *P=0.034, effect of treatment: P=0.149, genotype x treatment interaction: *P=0.045. Shank2+/+ vehicle injected n = 6, Shank2-/- vehicle injected n = 6, Shank2+/+ CNO injected n = 6, Shank2-/- CNO injected n = 7. Data information: All data are presented as mean ± SEM, NS: not significant. ",
    "ncbi_link": "Shank2: 210274"
  },
  {
    "caption": "a, Phase partitioning of Apg8. Wild-type and Δapg4Δapg8 cells producing Apg8FG and Δapg7 cells were subjected to phase partitioning (see Methods).",
    "ncbi_link": "apg4: 855498
apg7: 856576
apg8: 852200"
  },
  {
    "caption": "d, Thioester formation between Apg8 and Apg7. Cell extracts of Δapg7Δapg8 cells expressing Apg7-Myc and/or HA-Apg8 from 2µ plasmids were immunoprecipitated with anti-HA antibody, and immunoblotted (IB) with anti-Myc and anti-HA antibody. DTT-, no DTT; DTT+, 100 mM DTT; asterisk, Apg8-Apg7 conjugate.",
    "ncbi_link": "apg7: 856576
apg8: 852200"
  },
  {
    "caption": "b, Interaction between Apg8 and Apg7. Δapg7Δapg8 cells were transformed with APG7-Myc and/or APG8 on 2µ plasmids. Cell lysates were immunoprecipitated with anti-Myc antibody, and immunoblotted with anti-Myc or anti-Apg8 antibody. Apg8 co-immunoprecipitated with Apg7-Myc.",
    "ncbi_link": "apg7: 856576
APG7: 856576
apg8: 852200
APG8: 852200"
  },
  {
    "caption": "c, Effect of Apg8 C-terminal processing on the Apg8-Apg7 interaction. Δapg4 cells co-expressing Apg7-Myc and HA-Apg8 (FGR, FG and F) from 2µ plasmids. FGR, wild-type Apg8; FG, Apg8 lacking C-terminal arginine; F, Apg8 lacking C-terminal glycine and arginine. Cell lysates were immunoprecipitated with anti-HA antibody, and immunoblotted with anti-HA and anti-Myc antibody.",
    "ncbi_link": "apg4: 855498
Apg7: 856576
Apg8: 852200"
  },
  {
    "caption": "b, Interaction between Apg8 and Apg3. Lysates of Δapg3 cells expressing APG3 and/or Myc-APG8 from 2µ plasmids were immunoprecipitated with anti-Apg3 antibody, and immunoblotted with anti-Apg3 and anti-Myc antibody.",
    "ncbi_link": "apg3: 855741
APG8: 852200"
  },
  {
    "caption": "c, Effect of mutated Cys 234 in Apg3 on the interaction between Apg8 and Apg3. Lysates of Δapg3 cells expressing Myc-APG8 and either wild-type (wt) APG3 or mutant APG3 (C234S and C234A) from 2µ plasmids were immunoprecipitated with anti-Myc antibody, and immunoblotted with anti-Myc and anti-Apg3 antibodies.",
    "ncbi_link": "Apg3: 855741
apg3: 855741"
  },
  {
    "caption": "d, Thioester formation between Apg8 and Apg3. Δapg3, Δapg7 and Δapg10 cells were transformed with both Myc-APG8 and Apg3, or only Apg3, on 2µ plasmids. Cell extracts were immunoprecipitated with anti-Myc antibody, and subjected to immunoblot (IB) using anti-Myc and anti-Apg3 antibody. DTT-, no DTT; DTT+, 100 mM DTT; asterisk, Apg8-Apg3 conjugate; diamond, possible Myc-Apg8 dimer.",
    "ncbi_link": "apg10: 850684
apg3: 855741
Apg3: 855741
apg7: 856576
APG8: 852200"
  },
  {
    "caption": "a, Apg7 and Apg3 are necessary for attachment of Apg8 to PE. Δapg cell lysates were subjected to SDS-PAGE containing 6 M urea, and immunoblotted with anti-Apg8 antibody.",
    "ncbi_link": "Apg3: 855741
Apg7: 856576"
  },
  {
    "caption": "b, Autophagic activity in apg3 mutants. Wild-type, Δapg3 and apg3C243A cells were grown in rich medium (open bar) and subjected to nitrogen starvation for 4 h (filled bar). The autophagic activity of each cell was assessed by measuring the alkaline phosphatase activity. The apg3C243A mutant showed defective autophagy.",
    "ncbi_link": "apg3: 855741"
  },
  {
    "caption": "C)  ykt6ts pho8∆60 cells containing an empty plasmid, 3HA-Ykt6 or 3HA-tagged Ykt6 mutant variants as indicated were analyzed as in A).",
    "ncbi_link": "3HA: 
ykt6: 853638
Ykt6: 853638"
  },
  {
    "caption": "D) ykt6ts pho8∆60 cells containing an empty plasmid, 3HA-Ykt6, or ADH1 promoter driven 3HA-Ykt6 wild type or 3HA-tagged Ykt6 mutant variants as indicated were grown and Pho8∆60 activity was monitored as described in A).",
    "ncbi_link": "3HA: 
ADH1: 854068
ykt6: 853638
Ykt6: 853638"
  },
  {
    "caption": "A)  ykt6ts  cells containing centromeric plasmids as indicated were grown at permissive temperature (23 ºC), shifted to the restrictive temperature at 37 ºC for 1 hour before starvation for 1 hour at 37 ºC. Cells were lysed and the total extract (T) separated into a cytoplasmic (S) and a 100'000x g membrane pellet (P) fraction. Fractions were analyzed by anti-HA, anti-Tom70 and anti-Pgk1 Western blotting. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "ykt6: 853638"
  },
  {
    "caption": "B) vam3∆ or   ykt6ts vam3∆ cells containing the indicated centromeric plasmids were grown at permissive temperature (23 ºC), shifted to the restrictive temperature at 37 °C for 1 hour followed by 1 hour starvation in SD-N at 37 ºC. After cell lysis, samples were subjected to proteinase K (ProtK) and Triton X-100 (TX100) treatment as indicated and analyzed by anti-Ape1 Western blotting. Ape1*: proteinase K-resistant fragment of Ape1. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "vam3: 854273
ykt6: 853638"
  },
  {
    "caption": "C) Trichloroacetic acid extracts were prepared from  ykt6ts cells containing an empty plasmid, 3HA-Ykt6  wild type, or 3HA-tagged Ykt6 mutant variants. Cells were grown at the permissive temperature (23 ºC) to late exponential phase in selective medium, shifted to the restrictive temperature (37 °C) for 1 h preincubation and continued to grow at the restrictive temperature for another 4 hours before harvesting. Samples were analyzed by anti-CPY and anti-Pgk1 Western blotting. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "3HA: 
ykt6: 853638
Ykt6: 853638"
  },
  {
    "caption": "D) Exponentially growing ykt6ts cells at permissive temperature (23 ºC) containing centromeric plasmids as indicated were shifted to the restrictive temperature (37 ºC) for 1 hour before starvation for 4 hours in SD-N. Trichloroacetic acid  extracts were prepared. Lipidation of Atg8 was analyzed on a 15 % SDS-PAGE containing 6 M urea by anti-Atg8 and anti-Pgk1 Western blotting. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "ykt6: 853638"
  },
  {
    "caption": "A and B) GFP-Atg8 atg1∆, GFP-Atg8 atg1∆ vam3∆, GFP-Atg8 wild type, GFP-Atg8 vam3∆, GFP-Atg8 ykt6ts  or GFP-Atg8 ykt6ts vam3∆ cell containing centromeric plasmids as indicated were grown at permissive temperature (23 ºC), shifted to the restrictive temperature at 37 ºC for 2 hours before starvation for 1 hour at 37 ºC in SD-N. Representative microscopy images  are shown in A). GFP-Atg8 puncta per cell were quantified from 3 biological replicates (n≥100 cells) and the mean was plotted in B). Error bars are SD. Scale bar: 5 µm.",
    "ncbi_link": "GFP: 
atg1: 852695
Atg8: 852200
vam3: 854273
ykt6: 853638"
  },
  {
    "caption": "Autophagosomes were prepared from GFP-Atg8 vam3∆ pep4∆ or GFP-Atg8 ykt6ts vam3∆ pep4∆ cells containing centromeric plasmids as indicated. Cells were starved for 16 hours at the permissive temperature (23 °C) to allow formation of mature, closed autophagosomes and shifted for 1 hour to the restrictive temperature before harvesting. Vacuoles were isolated from Vph1-4xmCherry atg15∆ pep4∆ cells grown under rich conditions at 30 °C. Fusion reactions were incubated at the restrictive temperature (30 °C) for 2 hours. Representative  images are shown in C).",
    "ncbi_link": "GFP: 
mCherry: 
atg15: 850432
Atg8: 852200
pep4: 855949
vam3: 854273
ykt6: 853638"
  },
  {
    "caption": "Autophagosomes were prepared from GFP-Atg8 vam3∆ pep4∆ or GFP-Atg8 ykt6ts vam3∆ pep4∆ cells containing centromeric plasmids as indicated. Cells were starved for 16 hours at the permissive temperature (23 °C) to allow formation of mature, closed autophagosomes and shifted for 1 hour to the restrictive temperature before harvesting. Vacuoles were isolated from Vph1-4xmCherry atg15∆ pep4∆ cells grown under rich conditions at 30 °C. Fusion reactions were incubated at the restrictive temperature (30 °C) for 2 hours. The graph in D) shows the mean from at least three independent biological experiments. Error bars represent the standard deviation.",
    "ncbi_link": "GFP: 
mCherry: 
atg15: 850432
Atg8: 852200
pep4: 855949
vam3: 854273
ykt6: 853638"
  },
  {
    "caption": "The indicated strains were grown to late exponential phase at permissive temperature (23 ºC), shifted to the restrictive temperature at 37 °C for 1 hour followed by starvation in SD-N for 1 hour at 37 ºC. 3HA-Ykt6  and its mutant variants expressed from a centromeric plasmid were immunoprecipitated  (IP) and analyzed by anti-HA Western blotting. Co-precipitating proteins were analyzed by anti-Vam3 and anti-Vti1 Western blotting. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "3HA: 
Ykt6: 853638"
  },
  {
    "caption": "a) COS-7 cells expressing EGFP-tagged wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin exon 1 (green) for 48 h stained for endogenous mTOR (red) show mTOR in mutant aggregates.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(b) Double-labeling immunohistochemistry of huntingtin (EM48; green) and mTOR (red) in brain tissue of mice expressing mutant huntingtin.",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(d) Western blot of lysates from stable inducible PC12 cells 48 h after expression of wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin showing mTOR in the stacking gel (mTOR insoluble) in cells expressing mutant huntingtin.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(e) High-molecular-mass aggregates of mTOR in both PC12 (i) and COS-7 (ii) cells expressing mutant (Gln74; Q74) huntingtin. Blots of cell lysates from PC12 cells were probed with antibodies to phosphorylated mTOR (Ser2448; p-mTOR; iii) and to GFP (iv); both showed insoluble material in the stack.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(f) Cell lysates from stable inducible PC12 cells and transiently transfected COS-7 cells expressing wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin for 48 h were immunoprecipitated using antibody to GFP and immunoblotted with antibody to mTOR. Uninduced PC12 cells with mutant huntingtin (UI) and untransfected COS-7 cells (UT) were controls.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(g) Brain lysates from mice expressing mutant huntingtin (Tg) or control (Cont) littermates were immunoprecipitated with antibody to mTOR and immunodetected with an antibody recognizing the polyglutamine tract (IC2). Htt, huntingtin",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(a) Reduced levels of soluble mTOR (as a function of tubulin) in stable inducible PC12 cells expressing mutant (Gln74; Q74) huntingtin compared with those expressing wild-type (Gln23; Q23) huntingtin (four independent experiments; P 0.0001; unpaired t-test).",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(b) Reduced levels of soluble mTOR in brain lysates from mice expressing mutant huntingtin (M1, M2; n = 9) compared with age-matched wild-type littermates (C1, C2; n = 9; P 0.001, unpaired t-test).",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(c) COS-7 cells transiently transfected with wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin (green) labeled for endogenous 4E-BP1 (red).",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(e) Western blot of cell lysates from stable inducible PC12 cells transfected with wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin shows that cells expressing mutant huntingtin had 31% (± 4.3% s.e.) less phosphorylated S6K1 (top) relative to total S6K1 (bottom) than cells expressing wild-type huntingtin. (f) Similarly, cells expressing mutant (Gln74; Q74) huntingtin had 30% (± 4.5% s.d.) less phosphorylated 4E-BP1 (top) relative to total 4E-BP1 (bottom) than cells expressing wild-type (Gln23; Q23) huntingtin. Expression of wild-type and mutant huntingtin was induced for 48 h (e,f). (g) Cells expressing mutant (Gln74; Q74) huntingtin also had lower levels of phosphorylated forms of transiently transfected FLAG-tagged 4E-BP1 than cells expressing wild-type (Gln23; Q23) huntingtin. The multiple bands in 4E-BP1 (f,g) are due to its different phosphorylated species.",
    "ncbi_link": "4E-BP1: 1978
huntingtin: 3064"
  },
  {
    "caption": "(a) COS-7 cells expressing wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin (green) were labeled for S6 phosphorylated at Ser235 and Ser236 (red). Percentages of cells expressing wild-type or mutant huntingtin that did (+agg) or did not (−agg) contain aggregates were scored for negative staining for phosphorylated S6 (p-S6).",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(b) Brain sections from control (WT) and mice expressing mutant huntingtin (HD) were stained for phosphorylated S6 (red) and with antibody to huntingtin (EM48; green).",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(c,d) Impaired mTOR-dependent TOP translation in cells expressing mutant huntingtin. (c) PC12 cells expressing wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin were transfected with luciferase constructs containing 5′ untranslated sequence with (+) or without (−) a TOP sequence along with β-gal. Each bar represents the difference between the luciferase activities in the presence versus the absence of rapamycin. Data shown are from one representative experiment (of three) done in sextuplicate (error bars represent s.e.; raw data are given in Supplementary Fig. 4 online). (d) COS-7 cells were cotransfected with wild-type or mutant huntingtin, a nontypical TOP or control luciferase vector and β-gal. The experiment was done and analyzed as in c (raw data are given in Supplementary Fig. 4 online) (e-g) Relevance of mTOR sequestration to other polyglutamine expansion diseases",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(g) Staining for phosphorylated S6 (red) in COS-7 cells transiently transfected with mutant (ataxin Q92; green) or wild-type (ataxin Q2) ataxin-1 constructs. Results were significant and similar to those in a. Arrows in a, b, e and g show cells containing aggregates.",
    "ncbi_link": "ataxin: 6310
ataxin-1: 6310"
  },
  {
    "caption": "(a) LC3-II levels, which closely correlate with autophagic activity, were higher in mutant lines (expressing Gln74 huntingtin; Q74; lanes 3 and 4) than in wild-type lines (expressing Gln23 huntingtin; Q23; lanes 1 and 2). Actin was used as a loading control. Data are shown for two independent clonal lines expressing mutant or wild-type huntingtin. Quantification of the band intensity is shown in the right panel.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(b) Immunofluorescence analysis of COS-7 cells expressing wild-type (Gln23; Q23) or mutant (Gln74; Q74) huntingtin with antibody to LC3 showed more autophagic vacuoles in cells expressing mutant huntingtin that had aggregates (arrow). COS-7 cells without the primary antibody (negative) and COS-7 cells without any treatment (untreated) stained for LC3 are also shown. The numbers of EGFP-positive cells expressing wild-type or mutant huntingtin with (+agg) and without (−agg) aggregates that had higher numbers of autophagic vacuoles (>15-20 vesicles per cell) is shown in the graph. COS-7 cells grown in starvation medium (starvation) or treated with rapamycin (Rap) for 4 h to induce autophagy had more autophagic vacuoles (arrows).",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "(a) Activation of mTOR activity with rheb increases aggregation and toxicity of mutant (Gln74; Q74) huntingtin. COS-7 cells were cotransfected with a mammalian expression vector encoding rheb (or empty vector control) and mutant huntingtin for 48 h at a 3:1 mass ratio (rheb or empty vector to huntingtin) to ensure that almost all cells expressing huntingtin also expressed rheb. The percentages of EGFP-positive cells with aggregates or apoptotic nuclear morphology (as described previously) were markedly higher when rheb was overexpressed. Control cells express mutant huntingtin (green) without rheb. The middle panels show images captured at the same comparatively low gain to distinguish aggregates from soluble EGFP. The left panels show the same fields at a similar higher gain to indicate the total number of EGFP-positive cells (this shows that the effect seen in the middle panels is not due to loss of cells). Nuclear staining with DAPI (blue) is shown in the right panels. ***P 0.0001. Error bars represent s.e. for a representative triplicate experiment.",
    "ncbi_link": "huntingtin: 3064
rheb: 6009"
  },
  {
    "caption": "(b,c) Treatment with rapamycin rescues huntingtin-induced degeneration in flies 2 d after eclosion. Photographs of ommatidia of flies expressing mutant (Gln120; Q120) huntingtin treated with DMSO or rapamycin from the larval stage into adulthood. More rhabdomeres are visible in the ommatidia of flies treated with rapamycin. This effect is significant (P 0.0001; Mann-Whitney U test). At 2 d after eclosion, there is no reduction in the number of visible rhabdomeres in wild-type untreated flies (data not shown).",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "Open bars, mice treated with a placebo; filled bars, mice treated with CCI-779. (a-c) Behavioral tests in mice expressing mutant huntingtin after treatment at 16 weeks (CCI-779, n = 14; placebo, n = 14), 18 weeks (CCI-779, n = 10; placebo, n = 9), 20 weeks (CCI-779, n = 9; placebo, n = 7) and 22 weeks (CCI-779, n = 5; placebo, n = 6) of age. Scores are explained in Methods. Data for all time points are given in Supplementary Figure 13 online. (a) Tremors. Overall effect from all treated time points: P = 0.0006, odds ratio (OR) = 0.21, 95% confidence interval (95% c.i.) = 0.098-0.45. 16 weeks, P = 0.01; 18 weeks, P = 0.08; 20 weeks, P = 0.14; 22 weeks, P = 0.07. (b) Wire maneuver. Overall effect from all treated time points: P = 0.02, OR = 0.51, 95% c.i. = 0.29-0.92. 16 weeks, P = 0.29; 18 weeks, P = 0.40; 20 weeks, P = 0.003; 22 weeks, P = 0.008. (c) Grip strength. Overall effect from all treated time points: P 0.0001 OR = 12.73, 95% c.i. = 4.35-37.2. 16 weeks, P = 0.1827; 18 weeks, P = 0.0412; 20 weeks, P = 0.0021; 22 weeks, P = 0.0285.",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(d) Accelerating rotarod tests in mice expressing mutant huntingtin after treatment at 4 weeks, (CCI-779, n = 16; placebo, n = 17), 14 weeks (CCI-779, n = 11; placebo, n = 10), 16 weeks (CCI-779, n = 14; placebo, n = 14) and 18 weeks (CCI-779, n = 10; placebo, n = 9) of age. Overall effect from all treated time points: P = 0.035. 4 weeks, P = 0.227; 14 weeks, P = 0.012; 16 weeks, P = 0.0025; 18 weeks, P = 0.057. CCI-779 had no discernable effects on the performance of nontransgenic mice on any of these behavioral tests (data not shown). There was no difference in the male:female ratios of the groups treated with placebo or with CCI-779.",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(a) Weights of mice expressing mutant huntingtin (Tg) and nontransgenic (NT) littermates treated with CCI-779 or with a placebo. (b) Brain weights of mice expressing mutant huntingtin treated with CCI-779 (black bars) or with a placebo (white bars) and nontransgenic untreated littermates (gray bars) at 8 weeks (CCI-779, n = 3; placebo, n = 3; nontransgenic, n = 7; CCI-779 versus placebo, P = 0.023), 12 weeks (CCI-779, n = 2; placebo, n = 3; nontransgenic, n = 5; CCI-779 versus placebo, P = 0.90) and 16 weeks (CCI-779, n = 2; placebo, n = 3; nontransgenic, n = 2; CCI-779 versus placebo, P = 0.22) of age. (c) Ratio of brain weight to body weight of mice expressing mutant huntingtin treated with CCI-779 (black bars) or with a placebo (white bars) and nontransgenic untreated littermates (gray bars) at 8 weeks (CCI-779, n = 3; placebo, n = 3; nontransgenic, n = 7; CCI-779 versus placebo, P = 0.06), 12 weeks (CCI-779, n = 2; placebo, n = 3; nontransgenic, n = 5; CCI-779 versus placebo, P = 0.38) and 16 weeks (CCI-779, n = 2; placebo, n = 3; nontransgenic, n = 2; CCI-779 versus placebo, P = 0.56) of age.",
    "ncbi_link": "huntingtin: 15194"
  },
  {
    "caption": "(a) CCI-779 reduces aggregate load in mice expressing mutant huntingtin. Peroxidase immunohistochemistry of brains of mice expressing mutant huntingtin at 16 weeks of age. Mice treated with CCI-779 had fewer aggregates per unit area in the striatum than mice treated with a placebo. Overall cell staining in the tissues of mice treated with CCI-779 was weaker than in those treated with a placebo and in nontransgenic untreated littermates (data not shown). Aggregates, when visible, were smaller in mice treated with CCI-779 than in those treated with a placebo, as apparent in the higher magnification images of single cells with aggregate (bottom panels). Six coronal sections per mouse were analyzed; these corresponded to the bregma ± 1 mm. We counted aggregates in five different high-power fields (60× objective) per slide on each side of the brain, sampling fields from the dorsal to the ventral part of the striatum just underneath the external capsule. The striata of mice treated with CCI-779 had 70% fewer aggregates than the striata of mice treated with a placebo (P = 0.0001, two-tailed t-test).",
    "ncbi_link": "huntingtin: 3064
huntingtin: 15194"
  },
  {
    "caption": "A-E: HeLa/Ctrl (A), HeLa/STARD3 (B), HeLa/STARD3 S209A (C), HeLa/STARD3 S209D/P210A (D) and HeLa/STARD3 Conv-FFAT (E) cells were labeled with anti-STARD3 antibodies (magenta), anti-Lamp1 antibodies (green) and with the fluorescent cholesterol probe filipin (Cyan Hot). Nuclei are shown in gray (TO-PRO-3). Higher magnifications images (2x) of the area outlined in white are shown on the right. The filipin, STARD3 and Lamp1 merged image is labeled Overlay. Scale bars: 10 µm. Inset scale bars: 5 µm.",
    "ncbi_link": "STARD3: 10948"
  },
  {
    "caption": "F: Pearson's correlation coefficients between STARD3 and Lamp1 staining in HeLa/STARD3 cells. Each dot represents a single cell (34 cells from 4 independent experiments). Mean and error bars (SD) are shown. Note that STARD3 and Lamp1 signals are highly correlated.",
    "ncbi_link": "STARD3: 10948"
  },
  {
    "caption": "G: Relative fluorescence intensity of intracellular filipin signals in endosomes of HeLa/Ctrl, HeLa/STARD3, HeLa/STARD3 S209A, HeLa/STARD3 S209D/P210A and HeLa/STARD3 Conv-FFAT cells. Data are displayed as a Superplot (Lord et al, 2020) showing the relative filipin fluorescence intensity in endosomes of individual cells (small circles) from 6 independent experiments (mean of each experiment shown as a large circle). Independent experiments are color-coded. Means and error bars (SD) are shown as black bars. Kruskal-Wallis with Dunn's multiple comparison test (*P < 0.05; **P < 0.01; n=6 independent experiments).",
    "ncbi_link": "STARD3: 10948"
  },
  {
    "caption": "G-I: GFP-MOSPD2-expressing cells (green) were left untransfected (G) or transfected with Flag-STARD3 (H) and Flag-STARD3 S209A (I), and labelled using anti-Flag (magenta) antibodies. The subpanels on the right are higher magnification (3.5×) images of the area outlined in white. The Overlay panel shows merged green and magenta images. The Coloc panel displays a colocalization mask on which pixels where the green and the magenta channels co-localize are shown in white. Scale bars: 10 µm.",
    "ncbi_link": "Flag: 
STARD3: 10948"
  },
  {
    "caption": "B.  Western blot  analysis of hnRNP R in three independent HNRNPR  wildtype (+/+), heterozygous (+/-) and homozygous (-/-) HeLa  cell lines.",
    "ncbi_link": "HNRNPR: 10236"
  },
  {
    "caption": "E. RNA FISH  with a Cy3-labeled  oligo-dT   probe. DAPI  was used for nuclear staining. Scale bar: 10 µm. F. Quantification of mean fluorescence intensity of the Cy3  oligo-dT signal in (E). Data are mean with SD; ****P ≤ 0.0001; Mann-Whitney test (n = 129 cells for HNRNPR+/+ and n = 176 cells for HNRNPR-/-).",
    "ncbi_link": "HNRNPR: 10236"
  },
  {
    "caption": "I. Quantification of 7SK  RNA in subcellular fractions by qPCR. Data are mean with SD; **P ≤ 0.01, n.s. not significant; two-way ANOVA with Sidak's multiple comparisons test (n = 3 biological replicates).",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "J. Quantification of 7SK  RNA co-immunoprecipitating with  hnRNP A1 from subcellular fractions. Data are mean with SD; *P ≤ 0.05, n.s. not significant; two-way ANOVA with Sidak's multiple comparisons test (n = 3 biological replicates).",
    "ncbi_link": "7SK: 125050"
  },
  {
    "caption": "A, B. Western blot  analysis of Ser2-phosphorylated  and total RNA pol II levels in HNRNPR+/+ (A) and -/- (B) cells treated with DMSO  or CHX  for the indicated durations. GAPDH  and α-Tubulin served as loading control.",
    "ncbi_link": "HNRNPR: 10236"
  },
  {
    "caption": "G. Western blot  analysis of  Cyclin T1 levels in HNRNPR+/+ and -/- cells treated with DMSO  or MG132. α-Tubulin served as loading control. H. Quantification of relative expression levels of  Cyclin T1 in (G). Data are mean with SD; ***P ≤ 0.001, ****P ≤ 0.0001, n.s. not significant; two-way ANOVA with Sidak's multiple comparisons test (n = 3 biological replicates).",
    "ncbi_link": "HNRNPR: 10236"
  },
  {
    "caption": "I Multidimensional cancer genomics data analysis results showing cross-cancer YAP gene alteration. The histogram showed the frequencies of YAP gene mutation, deletion, and amplification across cancers. Data were extracted from TCGA database and analyzed using cBioPortal online analyzing tools. The results indicate that the highest alteration frequency of YAP gene occurs in cervical cancer.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "A, C, E Western blot analysis showing levels of YAP and phosphorylated YAP in ME180 cell lines [ME180-MXIV (control), ME180-YAP, and ME180-YAPS127A cells] (A); HT3 cell lines [HT3-MXIV (control), HT3-YAP, and HT3-YAPS127A cells] (C); and Ect1 cell lines [Ect1-MXIV (control), Ect1-YAP, and Ect1-YAPS127A cells] (E). β-Actin was used as a protein loading control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "B, D, F Growth curves of YAP-overexpressed ME180 cell lines [ME180-MXIV (control), ME180-YAP, and ME180-YAPS127A cells] (B); HT3 cell lines [HT3-MXIV (control), HT3-YAP, and HT3-YAPS127A cells] (D); and Ect1 cell lines [Ect1-MXIV (control), Ect1-YAP, and Ect1-YAPS127A cells] (F). Each point represents the mean ± SEM (n = 4). ***P < 0.0001, ME180-MXIV vs. ME180-YAP cells and ME180-MXIV vs. ME180-YAPS127A cells on day 8. ***P < 0.0001, HT3-MXIV vs. HT3-YAP cells and HT3-MXIV vs. HT3-YAPS127A cells on day 8. ***P < 0.0001, Ect1-MXIV vs. Ect1-Ect1-YAPS127A cells on day 4. *P < 0.0074, Ect1-MXIV vs. Ect1-YAP cells on day 4.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "G Western blot showing YAP levels in non-targeting control siRNA (siCtrl)- and YAP siRNA (siYAP)-transfected HT3 cells.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "H Proliferation of HT3 cells treated with control (siCtrl) or YAP siRNA (siYAP). Each point represents the mean ± SEM (n = 5). ***P < 0.001 compared with siCtrl (siCtrl vs. siYAP, P = 0.0002).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "A Representative images showing colonies formed by Ect1-MXIV, Ect1-YAP, and Ect1-YAPS127A cells after growth in soft agar for 9 days. Scale bar: 500 μm.B Quantitative data showing colony formation in Ect1-MXIV, Ect1-YAP, and Ect1-YAPS127A cells. Each bar represents mean ± SEM of five independent experiments. Bars with different letters are significantly different from each other (Ect1-MXIV vs. Ect1-YAP, P = 0.0003; Ect1-MXIV vs. Ect1-YAPS127A, P = 0.0002).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "C, E Representative images showing the anchorage-independent growth of YAP-expressing HT3 (C) and ME180 (E) cervical cancer cell lines. Anchorage-independent cell growth was determined by the soft agar colony formation assay. Scale bar: 500 μm.D, F Fluorescence-based quantitative analysis showing the differences of anchorage-independent growth in HT3-MXIV, HT3-YAP, and HT3-YAPS127A (D) and ME180-MXIV, ME180-YAP, and ME180-YAPS127A cells (F). The anchorage-independent cell growth was determined using a CytoSelect 96-Well Cell Transformation Assay kit, and data are presented as relative fluorescent units (RFU). Each bar represents mean ± SEM of four independent experiments. Bars with different letters are significantly different from each other (HT3-MXIV vs. HT3-YAP, P = 0.0002; HT3-MXIV vs. HT3-YAPS127A, P < 0.0001; ME-MXIV vs. ME-YAP, P = 0.0011; ME-MXIV vs. ME-YAPS127A, P = 0.0013).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "A, B Representative images of tumorxenografts of ME180-MXIV (MX, right flank), ME180-YAP (A) (YAP, left flank), and ME180-YAPS127A (B) (YAPS127A, left flank) cells implanted in athymic nude mice. Red lines indicate the edge of tumors.C The growth curve of humantumorxenografts derived from control (ME-MX) and YAP-overexpressing ME180cervical cancer cell lines (ME-YAP, ME-YAPS127A) implanted in the athymic nude mice. Each point represents mean ± SEM of six tumors (control n = 10).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "D Representative images showing the relative size of tumors from control and YAP-overexpressing ME180 cervical cancer cells.E The average weight of tumor xenografts from the control and YAP-overexpressing ME180 cell lines. Data were analyzed for significance using one-way ANOVA in GraphPad Prism 5 with Tukey's post hoc tests. Each bar represents the mean ± SEM (n = 10 for control, n = 6 for YAP and YAPS127A groups). Bars with different letters are significantly different from each other (MXIV vs. YAP, P = 0.0008; MXIV vs. YAPS127A, P < 0.0001).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "F Western blot analysis of YAP protein levels in the tumor xenografts derived from ME180-MXIV, ME180-YAP, and ME180-YAPS127A cells.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "G Expression of Ki67 in the tumor xenografts of ME180-MXIV, ME180-YAP, and ME180-YAPS127A cells implanted in athymic nude mice. Ki67 was visualized using an Alexa-488 (green)-conjugated secondary antibody. Actin was visualized using an Alexa-594 (red)-conjugated secondary antibody. Nuclei were stained with DAPI. Scale bar: 20 μm. Note the significant increase in the Ki67-positive cells in the ME180-YAP and ME180-YAPS127A tumor xenografts.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "H Western blot analysis showing YAP protein levels in ME180 cells transfected with lentiviral empty vector (shCtrl) or lentivirus-based YAP shRNAs (shYAP#1 or shYAP#2).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "I Representative images showing tumor xenografts derived from ME180-shCtrl cells (left flank) and ME180-shYAP#1 cells (right flank) (n = 6).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "J Representative images showing the relative size of tumors derived from ME180 cervical cancer cells transfected with control shRNA (left, shCtrl) or YAP shRNA#1 (right, shYAP#1) (n = 6).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "RT-PCR results showing that YAP stimulates the mRNA expressions of EGFR, AREG, and TGF-α in ME180 cervical cancer cell. Data were analyzed for significance using one-way ANOVA in GraphPad Prism 5 with Tukey's post hoc tests. Each bar represents mean ± SEM (n = 4). Bars with different letters are significantly different from each other (YAP mRNA: MXIV vs. YAP, P = 0.0003; MXIV vs. YAPS127A, P = 0.0001; EGFR mRNA: MXIV vs. YAP, P = 0.0066; MXIV vs. YAPS127A, P = 0.0003; TGF-α mRNA: MXIV vs. YAP, P = 0.0235; MXIV vs. YAPS127A, P = 0.0040; AREG mRNA: MXIV vs. YAP, P = 0.0002; MXIV vs. YAPS127A, P < 0.0001).",
    "ncbi_link": "AREG: 374
EGFR: 1956
TGF-α: 7039
YAP: 10413"
  },
  {
    "caption": "Real-time PCR determines the action of TGF-α and YAP levels on the mRNA expression of AREG. Each bar represents the mean ± SEM (n = 5). Bars with different letters are significantly different from each other (Ctrl vs. TGF-α, P < 0.0001; MXIV vs. YAP, P < 0.0001; MXIV vs. YAPS127A, P < 0.0001).",
    "ncbi_link": "AREG: 374
YAP: 10413"
  },
  {
    "caption": "Real-time PCR analysis showing that knockdown of YAP with YAP siRNA (siYAP) significantly suppressed TGF-α-induced (FBS 10%, TGF-α: 10 ng/ml for 48 h) AREG expression in ME180 cells. siCTRL, a non-targeting siRNA, was used as a negative control. Each bar represents the mean ± SEM (n = 5). Bars with different letters are significantly different from each other (siCTRL vs. siCTRL+TGF-α, P < 0.0001; siYAP+CTRL vs. siYAP+TGF-α, P < 0.0001; siCTRL+TGF-α vs. siYAP+TGF-α, P = 0.0067).",
    "ncbi_link": "AREG: 374
YAP: 10413"
  },
  {
    "caption": "Proliferation of ME180 cells (FBS 1%) treated with control (siCTRL) or YAP (siYAP) prior to treatment with control medium or TGF-α (10 ng/ml) for 108 h. Each bar represents the mean ± SEM (n = 4). Bars with different letters are significantly different from each other (siCtrl vs. siCTRL+TGF-α, P = 0.0058; siYAP+CTRL vs. siYAP+TGF-α, P = 0.1840; siCTRL+TGF-α vs. siYAP+TGF-α, P = 0.0013).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Quantitative data of the wound-healing assay showing the migration of ME180 cells that were treated with control (siCTRL) or YAP siRNA (siYAP) prior to treatment with or without TGF-α for 12 h. Each bar in bar graphs represents the mean ± SEM (n = 4). Bars with different letters are significantly different from each other (siCtrl vs. siCTRL+TGF-α, P < 0.0001; siYAP+CTRL vs. siYAP+TGF-α, P < 0.0001; siCTRL+TGF-α vs. siYAP+TGF-α, P = 0.0041).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Real-time PCR showing that treatment of ME180 cells with AREG for 24 h significantly increased AREG mRNA expression. Each bar represents mean ± SEM (n = 9). Bars with different letters are significantly different from each other (P < 0.0001).",
    "ncbi_link": "AREG: 374"
  },
  {
    "caption": "Real-time PCR showing that knockdown of YAP in ME180 cells with YAP siRNA (siYAP) significantly suppressed AREG-induced AREG mRNA expression. siCTRL (non-target siRNA) was used as a siRNA control. Each bar represents mean ± SEM (n = 4). Bars with different letters are significantly different from each other (siCTRL vs. siCTRL+AREG, P < 0.0001; siYAP+CTRL vs. siYAP+AREG, P < 0.0001; siCTRL+AREG vs. siYAP+AREG, P = 0.0037).",
    "ncbi_link": "AREG: 374
YAP: 10413"
  },
  {
    "caption": "Representative images showing the morphology of spheroids derived from ME180-siCtrl and ME180-siLATS1/2 cells growing in a 3D hanging-drop culture system for 10 days. Scale bar: 1.0 mm.",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "Quantitative data showing changes in the volume of spheroids derived from ME180-siCTRL and ME180-siLATS1/2 cells growing in a 3D hanging-drop culture system. Each bar represents mean ± SEM (n = 5). Bars with different letters are significantly different from each other (P = 0.0004).",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "Soft agar assay showing the effect of AG1478 and VTPF on colony formation in ME180-MXIV, ME180-YAP and ME180-YAPS127A cells. Scale bar: 500 μm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "AREG mRNA levels in HT3 cells incubated for 48 h with or without recombinant HPV E6. Each bar represents mean ± SEM (n = 5). Bars with different letters are significantly different from each other (P = 0.0042).",
    "ncbi_link": "AREG: 374"
  },
  {
    "caption": "Western blotting analysis showing the effect of HPV16E6 (400 nM, 48 h) on YAP protein levels in HT3 cells transfected with non-targeting control siRNA (siCtrl) or YAP siRNA (siYAP).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Effect of YAP on HPV16 E6 stimulation of HT3 cell proliferation. siCtrl: non-targeting control siRNA; siYAP: YAP siRNA; E6: 400 nM recombinant HPV16 E6, 48 h. Each bar represents mean ± SEM (n = 4). Bars with the same letters are not significantly different from each other (siCtrl vs. siCtrl+E6, P = 0.0232; siCtrl+E6 vs. siYAP+E6, P = 0.0011).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Knockdown of endogenous E6 in HeLa cells with HPV18 E6 siRNA (siE6) reduced YAP protein in HeLa cells, while knockdown of YAP with YAP siRNA (siYAP) in these cells had no effect on the mRNA level of HPV18 E6. siCtrl: non-targeting control siRNA.",
    "ncbi_link": "E6: 1489088
YAP: 10413"
  },
  {
    "caption": "Knockdown of endogenous HPV18 E6 in HeLa cells with HPV18 E6-specific siRNA (siE6) significantly suppressed mRNA expression of AREG. Each bar represents mean ± SEM (n = 4). Bars with different letters are significantly different from each other (siCtrl vs. siHPV18E6, P = 0.0181; siCtrl vs. siYAP, P = 0.0005).",
    "ncbi_link": "AREG: 374
E6: 1489088
YAP: 10413"
  },
  {
    "caption": "Knockdown of endogenous HPV18 E6 in HeLa cells with HPV18 E6-specific siRNA (siE6) significantly suppressed cell growth (n = 9, siCtrl vs. siHPV18E6, P = 0.0002; siCtrl vs. siYAP, P = 0.0004).",
    "ncbi_link": "E6: 1489088
YAP: 10413"
  },
  {
    "caption": "Concentrations of AREG in the culture medium of HeLa cells transfected with non-targeting control siRNA (siCTRL) or HPV18 E6 siRNA (siHPV18E6). Each bar represents mean ± SEM (n = 6). Bars with different letters are significantly different from each other (P = 0.0461).",
    "ncbi_link": "E6: 1489088"
  },
  {
    "caption": "Effect of YAP mRNA levels in HT3 cells treated with or without E6 (400 nM) for 60 min in McCoy's 5A with 1% serum. Data were normalized with 18S mRNA. Bars with same letters are not significantly different from each other (P > 0.05). n = 4, P = 0.9407.",
    "ncbi_link": "18S: 
YAP: 10413"
  },
  {
    "caption": "YAP mRNA levels in HT3 cells treated with or without E6 (400 nM) for 48 h in McCoy's 5A with 1% serum. mRNA levels were measured with real-time PCR. Data were normalized with 18S mRNA. Each bar represents mean ± SEM (n = 5). Bars with same letters are not significantly different from each other (P > 0.05) (P = 0.3233).",
    "ncbi_link": "18S: 
YAP: 10413"
  },
  {
    "caption": "Western blot results showing that knockdown of endogenous E6 in HeLa cells with HPV18E6 siRNA (siE6) reduced YAP protein levels, but increased SOCS6 protein levels.",
    "ncbi_link": "E6: 1489088"
  },
  {
    "caption": "Western blot analysis showing that knockdown of SOCS6 in HT3 cells with SOCS6 siRNA (siSOCS#1 and siSOCS6#2) increased total YAP protein, enhanced phosphorylation of YAP protein at serine 127, but suppressed phosphorylation of YAP at serine 397.",
    "ncbi_link": "SOCS6: 9306"
  },
  {
    "caption": "A-F Representative images showing expression of YAP (in red) in wild-type mousecervical tissues (n = 5) (A), HPV16E6-induced (C) and HPV16E6/E7-induced (E) mousecervicaltumor tissue (n = 4 each). Scale bars for (A), (C), and (E): 100 μm. High-resolution images showing the expression and cellular location of YAP in normal cervical tissues (B), HPV16E6-induced (D) and HPV16E6/E7-induced (F) mousecervicaltumor tissue. Scale bars for (B), (D), and (F): 25 μm.",
    "ncbi_link": "E6: 1489078
E7: 1489079"
  },
  {
    "caption": "D The Drd1 mRNA level in the spinal cord after DCP or vehicle treatment. * P < 0.05. Student's t-test. n = 8 mice/group.",
    "ncbi_link": "Drd1: 13488"
  },
  {
    "caption": "F-H Representative images show non-overlap of tdTomato with EGFP in the SDH of Drd1-tdTomato;Drd2-EGFP mice. Scale bar, 100 μm.",
    "ncbi_link": "EGFP: 
tdTomato: 
Drd1: 13488
Drd2: 13489"
  },
  {
    "caption": "N Co-localization of tdTomato fluorescence with vGluT2-probe. Scale bar, 50 μm. O FISH double-staining of Drd1-probe with vGluT2-probe. White arrows and arrowheads show double-labeled neurons and vGluT2 single-labeled neurons, respectively. Scale bar, 10 μm. P Staining of PAX2 in Drd1-tdTomato mice. Scale bar, 50 μm. Q Fluorescence of tdTomato and EGFP in the SDH of Drd1-tdTomato;Gad67-EGFP mice. Scale bar, 50 μm.",
    "ncbi_link": "EGFP: 
tdTomato: 
Drd1: 13488
Gad67: 14415
vGluT2: 140919"
  },
  {
    "caption": "D Single-cell RT-PCR shows the expression of Drd1, Grp, NeuN, and Gapdh mRNA in tdTomato+ neurons. N, negative control. * indicate Drd1+Grp+ neurons.",
    "ncbi_link": "tdTomato: 
Drd1: 13488
Gapdh: 14433
Grp: 225642
NeuN: 52897"
  },
  {
    "caption": "I Effect of DNQX, RC-3095, or vehicle on the spontaneous scratching of mice with spinal DRD1+ neurons expressing mCherry or hM3Dq and activated by CNO. ** P < 0.01, *** P < 0.001. One-way ANOVA followed by Bonferroni's test. n = 8 mice/group. Data information: Bars represent mean values. Error bars indicate the SEM.",
    "ncbi_link": "mCherry: 
M3Dq: 1131"
  },
  {
    "caption": "J Effect of DNQX, RC-3095, or vehicle on the scratching behaviors of mice with spinal DRD1+ neurons expressing mCherry or hM3Dq and activated by CNO in C48/80 model (left) or CQ model (right). * P < 0.05, ** P < 0.01, *** P < 0.001. One-way ANOVA followed by Bonferroni's test. n = 6 mice/group. Data information: Bars represent mean values. Error bars indicate the SEM.",
    "ncbi_link": "mCherry: 
M3Dq: 1131"
  },
  {
    "caption": "A-D Wild type (WT), single (Ltk-/- and Alk-/-) and double (DKO) knockout embryos were injected with BrdU on day E14.5 and fixed cortices analyzed at E17.5, P2 and P7. A-C Coronal sections of BrdU labeled WT and mutant cortices at the indicated ages. Dotted lines mark the upper and lower cortical limits determined for each section. The location of the cortical plate (CP), intermediate zone (IZ), subventricular/ventricular zone (SVZ/VZ) in E17.5 and P2 mice and Layers I-VI in P7 WT mice are indicated. Scale bars are 50 µm. B, D Quantitation in E17.5 (B) or P2 and P7 (D) cortices of BrdU-positive cells in the indicated bins (marked on left of images) is plotted. Data are presented as the mean ± SEM from 3 (DKO, Ltk-/-) or 2 (WT, Alk-/-) independent biological experiments (B) or 3 (DKO and WT) independent biological experiments (D). Statistical significance: ****p<0.0001, ***p<0.001, ** p<0.005, *p<0.05 by Student's t-test.",
    "ncbi_link": "Alk: 11682
Ltk: 17005"
  },
  {
    "caption": "C Representative images of dissociated WT and DKO cortical neurons, electroporated with plasmids encoding EGFP alone or together with HA-tagged LTK-WT. Cells were fixed 38 h after plating and then stained for Tau-1 (axons, red) and MAP2 (dendrites, green). Arrowheads mark axons. Scale bars are 20 µm. Quantitation of the percent of neurons with multiple, single and no axons in EGFP positive neurons is plotted. Data are presented as percent of neurons with multiple, single and no axons and are plotted as the mean ± SEM of 150 of neurons per condition from 3 independent biological experiments. Statistical significance: ****p<0.0001, **p<0.01, *p<0.05 by one-way ANOVA, Dunnett's test.",
    "ncbi_link": "EGFP: 
HA: 
LTK: 4058"
  },
  {
    "caption": "E Golgi stains of adult cortices in wild-type, single (Ltk-/- and Alk-/-) and double (DKO) knockout mice show severe defects in neuronal projections and the callosal tract. Representative coronal sections of cortical layers I-V in WT and DKO mice (left), Layers IV-V in WT, single and double knockout cortices (center) and higher magnification images of WT and DKO neurites (right). Examples of disrupted directional growth and extension of projections in pyramidal neurons in knockout mice are marked (red arrowheads).",
    "ncbi_link": "Alk: 11682
Ltk: 17005"
  },
  {
    "caption": "Representative images of cortical neurons fixed at 38 h and stained with Tau-1 (axons, red) and MAP2 (dendrites, green) are shown. Arrowheads mark axons. C, D Treatment of cortical neurons from WT or KO mice with PI3 kinase inhibitors reverses polarity defects caused by loss of Ltk/Alk. Dissociated E16 cortical neurons were treated with LY294002 (10 µM; C), BKM120 (1 µM; D) or DMSO control, 4 h after plating. : In quantitation of the percent of neurons with multiple, single or no axons is plotted as the mean ± SEM of n=150 neurons per condition from , C-WT) or 4 (C-DKO independent biological experiments. Statistical significance: ****",
    "ncbi_link": "Alk: 11682
Ltk: 17005"
  },
  {
    "caption": "F Inhibition of Igf-1r blocks neuronal migration in vivo. Pregnant E14 WT or DKO mice were injected (i.p) with BrdU and 24 h later were injected with PPP or saline as control. Brains from P2 pups were subjected to staining with anti-BrdU antibody. Quantitation in P2 cortices of BrdU-positive cells in the indicated bins (marked on left) is plotted. The location of the cortical plate (CP), intermediate zone (IZ), subventricular/ventricular zone (SVZ/VZ) in P2 mice and are indicated. Scale bars are 50 µm. Data in (F) are presented as the mean ± SEM from 3 (DKO) and 2 (WT) independent biological experiments. Statistical significance: ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05 by one-way ANOVA, Dunnett's test by Student's t-test (F), where WT vs WT+PPP or DKO vs DKO+PPP were compared.",
    "ncbi_link": "Igf-1r: 16001"
  },
  {
    "caption": "(E) In C. elegans, all conserved ciliary cluster genes with available mutants as well as genes of particular interest for which mutants were generated in the course of this study were screened using the dye-fill assay to test for cilium structural integrity. 12 amphid neurons in the head and 4 phasmid neurons in the tail, both featuring non-motile sensory cilia, stain with the lipophilic dye DiI. Failure to take up dye is an indicator of ciliary structural defects. IFT mutants such as osm-5(p813) tend to display dye-fill null phenotypes, while other ciliary mutants present weaker phenotypes. Phenotypes were scored using a scale from 0 (no dye-fill phenotype) to 4 (null).",
    "ncbi_link": "osm-5: 180585"
  },
  {
    "caption": "(B) Schematic and confocal microscopy images of scolopidia in chordotonal organ of the fly. Each scolopidium contains two cilia with their ends embedded in a cap cell. Scolopidium outline, cilia and ciliary dilation can be visualized by DIC. Immunofluorescence micrographs with Sas-4 and NompC antibodies used to mark basal bodies and ciliary tips, respectively. DIC images of flies depleted of candidate genes by RNAi reveal relatively few defects on par with IFT genes such as IFT140, with the exception of misplaced dilations for Cep135 and CFAP97D1 (arrows). Missing cilia (asterisks) as with SAS4 or IFT52 are not observed. NompC/Sas-4 staining reveals more subtle phenotypes, including mislocalized NompC signal (with CFAP97D1, Cep135, Elmod, Mapk15 and Tex9, arrowheads) and apparent ciliary structural defects (Cep104 and Cables1, arrows). At least 3 animals examined per condition.",
    "ncbi_link": "Elmod: 34633
Cep135: 39647
Cep104: 35241
CFAP97D1: 43171
Tex9: 37928
Cables1: 36513
Mapk15: 31877
IFT52: 33917
IFT140: 33230
SAS4: 40859"
  },
  {
    "caption": "(E) Mature sperm can be dissected from the seminal vesicle and motility analyzed using high speed video capture in dark field microscopy. Sinusoidal motion can be seen in wild type. In RNAi depletions of certain known motility genes (here IQUB and GAS8), this motion is reduced or even absent. Arrowheads mark position of individual bends in sequential frames. At least 3 movies made from different animals per condition.",
    "ncbi_link": "IQUB: 42629
GAS8: 31321"
  },
  {
    "caption": "(A, RNAi-mediated depletion/deletion of CABLES1, CCDC6, CEP104 in Drosophila chordotonal neurons (A) results in defects in ciliary ultrastructure similar to CEP135. In neurons, there is a loss of 9-fold symmetry towards the ciliary tips with displaced doublet microtubules (arrowheads) and axonemes frequently fail to reach the cap cell (asterisks). At least 3 animals examined per condition and tissue.",
    "ncbi_link": "CEP135: 39647
CEP104: 35241
CABLES1: 36513
CCDC6: 39903"
  },
  {
    "caption": "B) RNAi-mediated depletion/deletion of CABLES1, CCDC6, CEP104 and TEX9 in Drosophila sperm (B) results in defects in ciliary ultrastructure similar to CEP135. In sperm, there is a loss of the inner pair of microtubules (asterisks), a phenotype hitherto only associated with CEP135. At least 3 animals examined per condition and tissue.",
    "ncbi_link": "CEP135: 39647
CEP104: 35241
TEX9: 37928
CABLES1: 36513
CCDC6: 39903"
  },
  {
    "caption": "(E Localization interdependencies between CEP135, CEP104 and the novel components TEX9, CCDC6 and CABLES1 in spermatogenesis. CEP135 is required for the localization of TEX9, CCDC6 and CEP104 to mature basal bodies (E) n>6 basal body pairs per condition. Asterisks indicate statistically significant differences to the respective control (t-test, **P < 0.01,***P<0.001).",
    "ncbi_link": "CEP135: 39647"
  },
  {
    "caption": "F) Localization interdependencies between CEP135, CEP104 and the novel components TEX9, CCDC6 and CABLES1 in spermatogenesis. while CEP135 localization is independent of TEX9, CCDC6 and CABLES1 at all stages of spermatogenesis (F). Asterisks indicate statistically significant differences to the respective control (t-test, **P < 0.01,***P<0.001).",
    "ncbi_link": "TEX9: 37928
CABLES1: 36513
CCDC6: 39903"
  },
  {
    "caption": "(B). RNAi-mediated depletion/deletion of Drosophila CFAP97D1 and CFAP299 results in defects in ciliary ultrastructure in chordotonal neurons, including broken axonemes (asterisk) and perturbed 9-fold symmetry (arrowheads). At least 3 animals examined per condition.",
    "ncbi_link": "CFAP97D1: 43171
CFAP299: 41619"
  },
  {
    "caption": "(D) RNAi-mediated depletion/deletion of CFAP299 results in failure of membrane deposition around the developing sperm axoneme (arrowheads). At least 3 animals examined per condition.",
    "ncbi_link": "CFAP299: 41619"
  },
  {
    "caption": "(A, B) Full gene deletions of mapk-15 and elmd-1 in C. elegans result in both shortened cilia and shortened dendrites, combining the signature phenotypes of IFT and transition zone mutants (here kap-1;osm-3 and ccep-290;nphp-4 double mutants, respectively). Representative images of phasmid (tail) neurons expressing OSM-6:GFP (A) and quantitation of cilium and dendrite lengths (B) in control and mutant animals as indicated. n >20 animals for all conditions. Asterisks indicate statistically significant difference to wild-type (cilium lengths, t-test, ***P < 0.001, dendrite lengths, Wilcoxon Mann-Whitney test, ***P < 0.001). mapk-15;elmd-1 double mutants do not display phenotypes stronger than either single mutant (t-test and Wilcoxon Mann-Whitney test as above, not significant).",
    "ncbi_link": "ccep-290: 3565260
elmd-1: 175439
kap-1: 176041
mapk-15: 175857
nphp-4: 179620
osm-3: 177141"
  },
  {
    "caption": "mapk-15 and elmd-1 mutants display defects in ciliary ultrastructure. (C) Cross-sectional views through the amphid channel reveal defects in cilium extension in both mutants, with fewer cilia protruding into the channel (asterisks). (D) Quantitation of cilium extension defects at the level of the proximal and distal amphid channel.",
    "ncbi_link": "elmd-1: 175439
mapk-15: 175857"
  },
  {
    "caption": "mapk-15 and elmd-1 mutants display defects in ciliary ultrastructure. (E) Higher magnification views of individual cilia reveal defects (indicated by arrowheads) at the level of the proximal segment of the axoneme (fewer than 9 doublet microtubules), transition zone (disorganization of the central cylinder and overall architecture) and ciliary base (membrane blebs). Percentages reported in figure based on examination of 4 mapk-15 and 7 elmd-1 mutant animals.",
    "ncbi_link": "elmd-1: 175439
mapk-15: 175857"
  },
  {
    "caption": "Localization interdependencies between MAPK-15 and ELMD-1. (G) Loss of ELMD-1 results in a hyperaccumulation of MAPK-15 at the C. elegans ciliary base, while loss of MAPK-15 impairs localization of ELMD-1 Percentages reported in figure based on examination of >30 animals for each condition.",
    "ncbi_link": "ELMD-1: 175439
MAPK-15: 175857"
  },
  {
    "caption": "(E) Phenotypic characterization of organotypic models made with HaCaT WT or GALNT1/2/3 KO keratinocytes. IHC of tissue sections stained for differentiation marker keratin 10 (upper panel) or proliferation marker Ki67 (lower panel). Scale bar - 50 μm. Red arrows - flattened cells; red asterisks - K10-negative region in suprabasal/granular layers; purple asterisks - pyknotic nuclei; green asterisks - increase in Ki67 positive cells.",
    "ncbi_link": "GALNT1: 2589"
  },
  {
    "caption": "(F) Quantification of epidermal thickness of skin organotypic models. Epidermal thickness was measured in 5 distinct images (4 positions/image) of 4 clones of GALNT isoform KO or WT (4 different tissues) and is presented as averages +SD. Due to high ZFN KO phenotypic inter-clonal variation and to exclude off target effects, 5 clones of ZFN and 3 clones of CRISPR KO (each targeted by a different gRNA) were used for GALNT3 KO. ANOVA followed by Dunnet's multiple comparison test was used to compare mean epidermal thicknesses of different KOs to WT. * p ≤ 0.05; **** p ≤ 0.0001.",
    "ncbi_link": "CRISPR: 
GALNT3: 2591"
  },
  {
    "caption": "(G) Quantification of keratin 10-negative area in skin organotypic tissue sections. Keratin 10-negative area was measured in 5 distinct images of 4 clones of GALNT isoform KO or WT (4 different tissues) and is presented as averages +SD. Due to high ZFN KO phenotypic inter-clonal variation and to exclude off target effects, 5 clones of ZFN and 3 clones of CRISPR KO (each targeted by a different gRNA) were used for GALNT3 KO. ANOVA followed by Dunnet's multiple comparison test was used to compare mean areas of different KOs to WT. **** p ≤ 0.0001.",
    "ncbi_link": "CRISPR: 
GALNT3: 2591"
  },
  {
    "caption": "(A) Numbers of quantified O-glycopeptides identified with ETD fragmentation with either dimethyl labeling or TMT labeling approach in COSMC KO or WT background, respectively. (B) Numbers of differentially glycosylated peptides in the two approaches, using select filters on quantification values. ",
    "ncbi_link": "COSMC: 29071"
  },
  {
    "caption": "GalNAc-T1 affects the organization and function of the endomembrane system. HaCaT WT and GALNT1 KO cells were stained for intracellular trafficking markers (scale bar - 10 μm). (A) Clathrin; (B) Rab5; (C) Rab11.",
    "ncbi_link": "GalNAc-T1: 2589
GALNT1: 2589"
  },
  {
    "caption": "GalNAc-T1 affects the organization and function of the endomembrane system. (D) Steady state intracellular pH measurement in in HaCaT WT and GALNT1 KO cells. Data is presented as average ± SD of 2 independent experiments. ANOVA followed by Dunnet's multiple comparison test",
    "ncbi_link": "GALNT1: 2589
GalNAc-T1: 2589"
  },
  {
    "caption": "(E) GalNAc-T2 is important for cell to matrix adhesion. HaCaT WT and GALNT2 KO cells were used in a cell to matrix adhesion assay using plates coated with different ECM components. Data is presented as average + SD of 3 independent experiments and is normalized to WT. ANOVA followed by Dunnet's multiple comparison test was used to compare mean relative adhesion of 2 different clones of GALNT2 KOs to WT. * p ≤ 0.05; ** p ≤ 0.01.",
    "ncbi_link": "GALNT2: 2590
GalNAc-T2: 2590"
  },
  {
    "caption": "(F) Western blot for GalNAc-T2 specific target and hemidesmosome component COL17A1.",
    "ncbi_link": "GalNAc-T2: 2590"
  },
  {
    "caption": "(I) GalNAc-T2 may affect tight junction formation and integrity. Upper panel, TEM of WT and GALNT2 KO organotypic tissue sections, where tight junctions are marked with asterisks. Lower panel, IF staining of WT and GALNT2 KO for tight junction marker occludin (scale bar - 50 μm). Inserts depict 3x zoomed in partial images (scale bar - 50 μm).",
    "ncbi_link": "GALNT2: 2590
GalNAc-T2: 2590"
  },
  {
    "caption": "(J) Expression of cyclin A (green) in HaCaT WT and GALNT3 KO organotypic tissue, visualized by IF (scale bar - 20 μm).",
    "ncbi_link": "GALNT3: 2591"
  },
  {
    "caption": "(L-N) Co-culture of HaCaT WT or GALNT3 KO keratinocytes with N/TERT1 keratinocytes induces cellular differentiation. Cells co-cultured on coverslips were stained for cleaved Notch 1 intracellular domain (L), cytokeratin 10 (M), or GalNAc-T3 (N; inserts depict 2x zoomed in partial images (scale bar - 20 μm)). Green - relevant staining, red - N/TERT1 cells (labeled with CMTMTR), blue - DAPI, scale bar - 20 μm. Boundaries between HaCaT and N/TERT-1 cells in the green panel of (L) are marked with a dashed line.",
    "ncbi_link": "GALNT3: 2591"
  },
  {
    "caption": "Knockdown efficiency of two shRNAs against GPR56 (shGPR56weak and shGPR56strong) versus shLuc as negative control measured on protein level by flow cytometry in CD34+ CB  cells. Shown are representative FACS plots (left) and the percentage of GPR56+ cells of transduced GFP+ cells on day 5 (right panel). Biological N=4, unpaired t-test, bars and error bars represent mean and standard deviation. *** p<0.0005, ** p<0.005, * p<0.05.",
    "ncbi_link": "Luc: 
GPR56: 9289"
  },
  {
    "caption": "Integrative Genome Viewer (IGV) snapshot showing  ATAC-seq peaks along and upstream of the  VWF  gene in GPR56high vs. low samples (top, average peak size of 10 GPR56high (turquoise) and 15 GPR56low samples (violet)), RNA-seq  reads of the same location in  AML samples with high (n=9) versus low (n=11)  GPR56 expression (two middle tracks), and RNA-seq reads of shLuc  versus GPR56 knockdown CD34+ cells (3 bottom tracks, one of two replicates shown for each condition). Track height was group-scaled. Dashed vertical lines indicate  binding sites for the annotated TFs. TFBS: transcription factor  binding site derived from the HOCOMOCO v10 database; TSS: transcription start site. TFs in blue  bind to differentially accessible chromatin  regions.",
    "ncbi_link": "Luc: 
GPR56: 9289
VWF: 7450"
  },
  {
    "caption": "Volcano plot of differential transcription factor (TF) motif accessibility (activity) in  GPR56high (turquoise) vs GPR56low (violet) samples and their corresponding adjusted p-values determined with diffTF. Highlighted are TFs whose RNA expression was also positively or negatively affected by GPR56  KD in the RNA-seq dataset.",
    "ncbi_link": "GPR56: 9289"
  },
  {
    "caption": "Violin plots showing geometric mean (horizontal line) and individual values (circles) of the engraftment  levels of different hematopoietic cell  types in the bone marrow  of NSG mice 20 weeks after transplantation of CB CD34+ cells following overnight-infection with shGPR56strong (turqouise) and shGPR56weak (gray) versus shLuc control (violet). Shown are percentages of indicated populations, which are also co-positive for  human CD45 and GFP, relative to all harvested  bone marrow cells. HSPC: CD34+SSClowCD33-CD19-, B precursor: CD34+CD19+CD33-, myeloid progenitor (myelo. prog.): CD34+CD33+CD19-, mature B cells: CD19+CD34-,  mature myeloid cells: CD33+CD19-CD34-. Multiple unpaired t-tests of log-transformed values, p-values were Benjamini and Hochberg corrected (padj), * padj<0.05, ** padj<0.005, *** padj<0.0005.",
    "ncbi_link": "Luc: 
GPR56: 9289"
  },
  {
    "caption": "Adhesion of control and GPR56 KD K562  cells on   fibronectin-functionalized substrates. Left: Overlay of phase contrast and microinterferometry images of control (above) and GPR56 KD cells (below). The area of tight adhesion extracted by microinterferometry is highlighted in turquoise and violet, respectively. Right: Comparison of adhesion areas extracted by microinterferometry, reduction of adhesion area by factor 1.9 in GPR56 KD cells (p = 1.0 x 10-10, two-sided Mann-Whitney test, box plots showing medians, quartiles, and outliers according to the Tukey method). Technical replicates Ncontrol = 71, Technical replicates NKD = 104, scale bar 10 µm.",
    "ncbi_link": "GPR56: 9289"
  },
  {
    "caption": "  β-catenin protein expression in K562  cells infected with shGPR56strong or shLuc negative control in presence and absence of Wnt3a (representative  Western Blot (above) and quantification after normalization to  GAPDH (below). Shown is fold-change compared to shLuc in control media, bars and error bars represent mean and standard deviation of three biological replicates, unpaired t-test).  ",
    "ncbi_link": "Luc: 
GPR56: 9289"
  },
  {
    "caption": "Left: Representative  immunofluorescence (IF) images showing  primary  cilium formation in  RPE  cells upon starvation after infection with shLuc (above) or shGPR56strong (below). The  non-motile primary cilium  is visualized using antibodies against γ-tubulin, which stains the basal body, and the ciliary membrane marker ARL13B. DAPI indicates the  nucleus. Images on the right show selected cells at 3 x magnification. Brightness was increased in all images to enhance visibility of cilia. Right: Percentage of RPE-1  cells with primary cilium in shLuc vs. shGPR56strong RPE-1 cells at different time points after the start of serum starvation. Unpaired t-test, bars and error bars represent mean and stdev of three biological replicate wells. **** p<0.0001, *** p<0.0005, ** p<0.005, * p<0.05.",
    "ncbi_link": "Luc: 
GPR56: 9289"
  },
  {
    "caption": "B, GFP and Trnp1 immunostaining with DAPI labelling in E14 cortical cells transfected for 24 h with plasmids (indicated by arrows) expressing the different truncated/mutant forms of Trnp1 and GFP showing Trnp1 localization.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "C, WB of cytoplasmic and nuclear enriched fractions of P19 cells transfected with the different truncated/mutant forms of Trnp1 for 24h. Hist1 and actin serve as loading controls for nuclear and cytoplasmic fractions, respectively. The values under the anti-Trnp1 blots indicate the percentage of the signal relative to the control set to 100% after normalization by α-actin (Image J quantification). The values under the anti-actin and anti-Hist1 blots indicate the percentage of the signal considering that nuclear and cytoplasmic fractions together is 100%.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "E, Co-IP with anti-FLAG magnetic beads and WB with anti-Trnp1 antibodies showing that FLAGTrnp1 interacts with the GFP-fusion and the ∆1-16Trnp1 proteins but not with other truncated Trnp1 proteins indicating IDRs are crucial for Trnp1 homo-oligomerization. Samples were collected 24h after transfection of P19 cells with plasmids expressing the indicated proteins depicted in the panel.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "H, Histogram depicting the percent of proliferating (Ki67+) cells transfected for 24 h with plasmids expressing control (GFP) or Trnp1-IRES-GFP and its different mutant/truncated forms-IRES-GFP in dissociated E14 cortical cells. Biological replicates: GFP=21; Trnp1=15; FLAGTrnp1=10; mutCC=5; ∆1-16=7; ∆1-1-56, ∆1-97, ∆1-140=3, ∆95-223=5 and ∆140-223=4.",
    "ncbi_link": "FLAG: 
GFP: 
Trnp1: 69539"
  },
  {
    "caption": "E-G, Bar and dot plots of the proportion of proliferating (Ki67+) cells (E), the number of NSCs (Pax6+) (F) and the proportion of proliferating (BrdU+) TAPs (Tbr2+)(G) as in A-C showing a significant increase in proliferating NSCs upon Trnp1 IUE compared to control or ∆1-16Trnp1 proteins (E- F) and a significant decrease in proliferating TAPs upon Trnp1 IUE and increase upon ∆1-16Trnp1 IUE compared to control (G) at E15, 2 days after IUE.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "B-C, Volcano plot showing the mean difference of the protein iBAQ between FLAGTrnp1 (B) and FLAG∆1-16Trnp1 (C) interacting proteins versus control plotted against the p-value. Proteins used to experimentally confirm the MS results are indicated with squares and the protein name in (B).",
    "ncbi_link": "FLAG: 
Trnp1: 69539"
  },
  {
    "caption": "(E) in the nucleus of P19 cells transfected with plasmids expressing Trnp1-IRES-GFP or GFP in control cells FACS sorted and fixed 24 h after transfection. Scale bars, 2 µm (D) and 1 µm (C and E).",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "F, WB of lysates from P19 cells transfeted for 24h with plasmids expressing GFP only or Trnp1-IRES-GFP with antibodies indicated.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "B-C, Analysis of the number (B) and the total area (C) of the GFP-Fbl1 foci in P19 cells expressing the constructs indicated for a period of 360 minutes. Band width represents SEM and grey areas represent time points with significant differences between the control and the Trnp1 expressing conditions. The ∆1-16Trnp1 expression does not show any statistical difference compared to the control condition.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "E, Volcano Plot illustrating the length of M-phase from condensation to de-condensation of chromosomes in minutes. Each dot represents an individual cell from 3 different biological replicates. GFP=61 cells, Trnp1=62 cells and ∆1-16Trnp1: 40 cells.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "G, Bar and dot plots depicting the proportion of GFP+ NSCs (Pax6+) in mitosis (pHH3+) showing a significant decrease 24h after Trnp1 compared to control IUE. N= 4 brains from 2-3 different litters.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "D-F Violin plots depicting the nuclear size (D) nucleoli number (E) and nucleoli size (F) from cells electroporated as in A-C with the constructs and the areas indicated on the x-axis. Note that in Trnp1, but not ∆1-16Trnp1, overexpression is sufficient to significantly increase nucleolar size in the non-VZ (where most cells lack endogenous Trnp1). N=10 cells per region from 6 different control and Trnp1-IRES-GFP electroporated embryos and N=15 per region from 3-4 different ∆1-16Trnp1-IRES-GFP electroporated embryos from at least 4 litters.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "I-K Violin plots depicting the nuclear size (D) nucleoli number (E) and nucleoli size (F) from cells electroporated as in G-H with the constructs and the areas indicated on the x-axis. Note that Trnp1 knockdown significantly decreases nucleolar size in the VZ (where most cells express endogenous Trnp1). N=10 cells per region from 7 embryos per condition from at least 4 litters.",
    "ncbi_link": "Trnp1: 69539"
  },
  {
    "caption": "D-E, Violin plots depicting the number (D) and size (E) of condensed chromatin spots from cells electroporated as in A-C. Note that Trnp1 overexpression is sufficient to significantly increase the size of condensed chromatin spots, while the ∆1-16Trnp1 acts as a dominant negative reducing the number and size of heterochromatin spots. N=10 cells per region from 5 embryos for GFP and Trnp1 and 8-15 cells from 4 embryos for ∆1-16Trnp1 of at least 4 litters. Each dot represents a cell.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "G-H Translation assay using OPP-click reaction in P19 cells transfected for 24 hours with GFP, Trnp1-IRES-GFP or ∆1-16Trnp1-IRES-GFP plasmids and analyzed by immunofluorescence (G) or FACs sorting (H) . Graph in (G) is representative from three different biological replicates. Each dot represents a cell. Control=102; Trnp1=126; ∆1-16Trnp1=97. Graph in (H) shows analysis of 2,000 transfected cells from 1 representative experiment with 2 biological replicates for control and 3 biological replicates for Trnp1 and ∆1-16Trnp1 conditons. The same FACs sorting experiment was repeated two more times. The dotted vertical line shows the mean of the OPP click signal for each condition.",
    "ncbi_link": "GFP: 
Trnp1: 69539"
  },
  {
    "caption": "I, Bar and dot plots depicting rRNA transcription for the 18S, 28S, 45S and 47S measured by qPCR in P19 cells transfected for 24h with plasmids expressing Trnp1-IRES-GFP or ∆1-16Trnp1-IRES-GFP compared to control cells expressing GFP . Each dot represents a biological replicate. N=4 for each condition.",
    "ncbi_link": "47S: 
GFP: 
18S: 19791
28S: 236598
45S: 100861531
Trnp1: 69539"
  },
  {
    "caption": "A: mRNA analysis of expression of endothelial (Tie2, CD31, Cdh5), epithelial (Cdh1), and early hematopoietic (Scl, CD41) marker genes in the indicated sorted cell populations. Error bars represent standard deviation (SD), n=3. Student's t-test. *p<0.05.",
    "ncbi_link": "Cdh1: 12550
Cdh5: 12562
CD41: 16399
CD31: 18613
Scl: 21349
Tie2: 21687"
  },
  {
    "caption": "B: Confirmation of the purity of sorted populations by qRT-PCR: c-Kit is highly expressed only in the c-Kit+ (D20LSK and D20LK) populations, and Sca1 is highly expressed only in the in Sca1+ (D20LSK and D20LS) populations. Error bars represent standard deviation (SD), n=3. Student's t-test. *p<0.05.",
    "ncbi_link": "Sca1: 20238
c-Kit: 16590"
  },
  {
    "caption": "C: qRT-PCR analysis of Gata1, Gata2, Lyz2, and Scl expression in the sorted cell populations on day 20. Error bars represent standard deviation (SD), n=3. Student's t-test. *p<0.05.",
    "ncbi_link": "Gata1: 14460
Gata2: 14461
Lyz2: 17105
Scl: 21349"
  },
  {
    "caption": "E: Heat map showing depletion of shRNAs targeting Cdc and Cdk genes in all day 20 samples.",
    "ncbi_link": "Cdc: 
Cdk: "
  },
  {
    "caption": "A: The E14tg2a ESCs were transduced with lentiviral shRNAs targeting genes Esrra, S100a8, or Hcfc2 and induced to form EBs. The day 6 EB cells were analyzed by flow cytometry to measure the Mesoderm-Endothelium cells (Flk1+/Cxcr4-) and Endoderm cells (Cxcr4+/Flk1-). The percentages of Mesoderm-Endothelium cells (Flk1+/Cxcr4-) were decreased on day 6 with shRNA knockdown of Group XII genes Esrra, S100a8, and Hcfc2 compared to control as quantified by flow cytometric analysis.B: Knockdown of Esrra, S100a8, and Hcfc2 showed that the ratios of percentage of Mesoderm-Endothelium population vs Endoderm population were decreased as measured by Flk1+/Cxcr4- vs. Flk1-/Cxcr4+ on day 6. The data were generated based on the quantification of flow cytometry analyses. Error bars represent standard deviation (SD), n=2. Student's t-test, *p<0.05.",
    "ncbi_link": "Esrra: 26379
Hcfc2: 67933
S100a8: 20201"
  },
  {
    "caption": "C: The E14tg2a ESCs were transduced with lentiviral shRNAs targeting genes Atp5g3, Bub1b, Eci1, or Dis3l and induced to form EBs. The day 6 EB cells were analyzed by flow cytometry to measure the Mesoderm-Endothelium cells (Flk1+/Cxcr4-) and Endoderm cells (Cxcr4+/Flk1-). Flow cytometric analysis showed that Endoderm cells (Cxcr4+/Flk1-) were deceased while Mesoderm-Endothelium cells (Flk1+/Cxcr4-) were slightly increased in the cells with shRNA knockdown of Group XI genes Atp5g3, Bub1b, Eci1, and Dis3l compared to control.D: Knockdown of Atp5g3, Bub1b, Eci1, or Dis3l led to increase of Mesoderm-Endothelium/Endoderm population ratio as quantified based on the flow cytometry data. Error bars represent standard deviation (SD), n=3. Student's t-test, *p<0.05.",
    "ncbi_link": "Atp5g3: 228033
Bub1b: 12236
Dis3l: 213550
Eci1: 13177"
  },
  {
    "caption": "E: The E14tg2a ESCs were transduced with lentiviral shRNAs targeting genes Wbp5, Rbm26, Gdpd4, and Nrxn1 and differentiated towards HSPCs. The differentiated cells on day 20 were analyzed by flow cytometry. Silencing of group IV genes including Wbp5, Rbm26, Gdpd4, and Nrxn1 decreased overall LK, LS, and LSK population on day 20.F: Quantification of LK+LSK+LS cell fractions with Wbp5, Rbm26, Gdpd4, and Nrxn1 silencing based on flow cytometric analyses. Error bars represent standard deviation (SD), n=2. Student's t-test, *p<0.05.",
    "ncbi_link": "Gdpd4: 233537
Nrxn1: 18189
Rbm26: 74213
Wbp5: 22381"
  },
  {
    "caption": "G: The E14tg2a ESCs were transduced with lentiviral shRNAs targeting genes Ap2a1, Mettl22, Lrsam1, or Hal and differentiated towards HSPCs. The differentiated cells on day 20 were analyzed by flow cytometry. Flow cytometric analysis showed notable reduction of LSK population on day 20 with Group X genes Ap2a1, Mettl22, Lrsam1, or Hal knockdown.H: Quantification of flow cytometric analyses showed knockdown of Ap2a1, Mettl22, Lrsam1, and Hal significantly impaired generation of LSK population on day 20 in vitro compared to control. Error bars represent standard deviation (SD), n=3. Student's t-test, *p<0.05.",
    "ncbi_link": "Ap2a1: 11771
Hal: 15109
Lrsam1: 227738
Mettl22: 239706"
  },
  {
    "caption": "D: Validation of the involvement of Group X target genes Lrsam1, Ap2a1, Mettl22, and Hal in zebrafish hematopoiesis by MO-mediated knockdown. Whole-mount in situ hybridization of Runx1 and c-Myb expression is shown at 26 hpf and 30hpf, respectively. Prdm16 knockdown serves as a positive control. Note that nonspecific staining for Runx1 and c-Myb was largely unaffected by targeted MO knockdown, whereas HSC markers Runx1 and c-Myb staining were notably reduced in discrete cells in the ventral region of the dorsal aorta (arrows). Scale bar = 100 µm.",
    "ncbi_link": "Ap2a1: 558153
Hal: 100004331
Lrsam1: 562066
Mettl22: 796066
c-Myb: 30519
Prdm16: 559174
Runx1: 58126"
  },
  {
    "caption": "A: Representative flow cytometric analysis showed that CD34+cells were significantly decreased at 5dpi with knockdown of AP2A1, METTL22, LRSAM1, or HAL. The human cord blood CD34+cells were transduced with pLKO-shRNAs targeting human AP2A1, METTL22, LRSAM1, or HAL and cultured for 5 days. Then, the flow cytometric analysis was performed to examine the percentage of CD34+cells in culture.B: Quantification of CD34+cells at 5dpi with knockdown of AP2A1, METTL22, LRSAM1, and HALshowed significant decrease of CD34+ cells compared to control. Error bars represent standard deviation (SD) from duplicates, *p<0.05.",
    "ncbi_link": "AP2A1: 160
HAL: 3034
LRSAM1: 90678
METTL22: 79091"
  },
  {
    "caption": "C: Flow cytometric analysis showed CD34+/CD90+cells were strikingly decreased at 5dpi with knockdown of AP2A1, METTL22, LRSAM1, and HAL.D: Quantification of CD34+CD90+cells at 5dpi with knockdown of AP2A1, METTL22, LRSAM1, and HALshowed significant decrease of CD34+CD90+cells compared to control. Error bars represent standard deviation (SD) from duplicates, *p<0.05.",
    "ncbi_link": "AP2A1: 160
HAL: 3034
LRSAM1: 90678
METTL22: 79091"
  },
  {
    "caption": "B-F Jejunal spheroids were cultured in differentiation medium containing 0-1,000 nM dmPGE2 or Iloprost. (E) Quantification of the average expression ± s.e.m. of Cldn4mRNA relative to the 0 nM treatment group (n = 3 independent experiments).",
    "ncbi_link": "Cldn4: 12740"
  },
  {
    "caption": "A Quantification of the average expression ± s.e.m. of Ptger1, Ptger2, Ptger3, Ptger4, and Ptgir mRNAs in whole-thickness lung, ileum or colon tissues or in jejunal spheroids cultured in stem cell (Stem), WAE (dmPGE2) or enterocyte (EP4i) medium (n = 3 independent experiments). Data are presented as fold change compared to lung tissue. n.d., not detected.",
    "ncbi_link": "Ptger1: 19216
Ptger2: 19217
Ptger3: 19218
Ptger4: 19219
Ptgir: 19222"
  },
  {
    "caption": "B-D Jejunal spheroids were cultured in differentiation medium with DMSO only or with 1 µM dmPGE2 and pharmacological inhibitors of EP1 (EP1i, SC 51322), EP2 (EP2i, PF 04418948), EP3 (EP3i, L-798,106) or EP4 (EP4i, L-161,982) at a concentration of 10 µM or an equivalent volume of DMSO vehicle. **p<0.01, ***p<0.001, ****p<0.0001 compared to the DMSO only group by one-way ANOVA and Dunnett's post-test. (D) Quantification of the average expression ± s.e.m. of Cldn4 mRNA relative to stem cellspheroids (n = 3 independent experiments).",
    "ncbi_link": "Cldn4: 12740"
  },
  {
    "caption": "E, F Tat-Cre mediated recombination of Ptger4flox/flox (fl/fl) jejunal spheroids to generate Ptger4flox/Δ (fl/Δ) and Ptger4Δ/Δ (Δ/Δ) spheroid lines. (E) Schematic and representative PCR genotyping results. M, marker lane. bp, base pairs. (F) Quantification of the average expression ± s.e.m. of Ptger4 mRNA in spheroids cultured in stem cell media relative to fl/fl genotype (n = 3 independent experiments). **p<0.01, ****p<0.0001 by 2-way ANOVA and Dunnett's multiple comparisons post-test with the EP4i-treated fl/fl group set as the control.",
    "ncbi_link": "Ptger4: 19219"
  },
  {
    "caption": "G-I Ptger4flox/flox, Ptger4flox/Δ and Ptger4Δ/Δ spheroids were cultured in differentiation medium with 1 µM dmPGE2 or 10 µM EP4i. *p<0.05, **p<0.01, ****p<0.0001 by 1-way ANOVA and Tukey's post-test. (G) Representative bright-field images. Scale bars, 200 µm. (H) Quantification of average spheroid area ± s.e.m. (n = 4 images per group from two independent experiments) relative to EP4i-treated Ptger4flox/flox spheroids.",
    "ncbi_link": "Ptger4: 19219"
  },
  {
    "caption": "G-I Ptger4flox/flox, Ptger4flox/Δ and Ptger4Δ/Δ spheroids were cultured in differentiation medium with 1 µM dmPGE2 or 10 µM EP4i. *p<0.05, **p<0.01, ****p<0.0001 by 1-way ANOVA and Tukey's post-test. (I) average expression ± s.e.m. of Cldn4 mRNA (n = 3 independent experiments) relative to EP4i-treated Ptger4flox/flox spheroids.",
    "ncbi_link": "Cldn4: 12740
Ptger4: 19219"
  },
  {
    "caption": "J-L Humanileal spheroids were cultured in differentiation medium with 1 µM dmPGE2 or 10 µM EP4i. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 by 1-way ANOVA and Tukey's post-test. (L) the average expression ± s.e.m. of CLDN4 mRNA (n = 3 independent donor lines) relative to stem spheroids.",
    "ncbi_link": "CLDN4: 1364"
  },
  {
    "caption": "G Graph of the fold change in background-subtracted luminescence ± s.e.m. (relative to 0 hr measurement) of Cdc25A-CBRLuc spheroids (n = 3 independent experiments with 4 technical replicates). ****p<0.0001 for dmPGE2- and EP4i-treated spheroids compared to stem cells by repeated measures 2-way ANOVA (variable = treatment). p<0.001 at the 16 hr, 20 hr and 24 hr time points by Dunnett's post-test comparing dmPGE2-treated and EP4i-treated spheroids to the stem cell control.",
    "ncbi_link": "Cdc25A: 12530"
  },
  {
    "caption": "H Quantification of the average expression ± s.e.m. of Lgr5 and Mki67 mRNAs in jejunal spheroids cultured in stem cell (Stem) or in differentiation medium with the indicated supplements relative to the stem cell group (n = 3 independent experiments). **p<0.01, ****p<0.0001 by one-way ANOVA and Dunnett's post-test. n.d., not detected.",
    "ncbi_link": "Lgr5: 14160
Mki67: 17345"
  },
  {
    "caption": "E, F Jejunal spheroids were cultured as in Figure 2B-D. Quantification of the average expression ± s.e.m. of Dpcr1 (E) and Cd55b mRNAs relative to DMSO group (n = 3 independent experiments). *p<0.05, ****p<0.0001 by one-way ANOVA and Dunnett's post-test.",
    "ncbi_link": "Cd55b: 13137
Dpcr1: 268949"
  },
  {
    "caption": "B, C Jejunal spheroids were cultured as indicated. (B) Quantification of the average expression ± s.e.m. of Fabp1, Ace2, and Maoa mRNAs (n = 3 independent experiments). *p<0.05, **p<0.01 by one-way ANOVA and Tukey's post-test.",
    "ncbi_link": "Ace2: 70008
Fabp1: 14080
Maoa: 17161"
  },
  {
    "caption": "A-D Quantification of the average expression ± s.e.m. of Dpcr1 and Cd55b mRNAs (A, C, E) or Fabp1 and Ace2 mRNAs (B, D, F) in jejunal spheroids cultured in differentiation medium containing EP4i or dmPGE2. (A, B) Gene expression analyzed 2, 6, 12 or 24 hours after the start of treatment (n = 3 independent experiments). ***p<0.001, ****p<0.0001 comparing the two treatment groups and †p<0.05, †††p<0.001, ††††p<0.0001 compared to the 2 hr time point of the same medium by 2-way ANOVA and Sidak's multiple comparisons test. (C, D) Gene expression was analyzed after culturing spheroids in EP4i (E) or dmPGE2 (P) for the first 12 hours followed by wash out and re-feeding with EP4i or dmPGE2 for the second 12 hours as shown (n = 3 independent experiments). *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001 by one-way ANOVA and Dunnett's post-test.",
    "ncbi_link": "Ace2: 70008
Cd55b: 13137
Dpcr1: 268949
Fabp1: 14080"
  },
  {
    "caption": "E, F Gene expression was analyzed in Ptger4flox/flox, Ptger4flox/Δ and Ptger4Δ/Δspheroids and expressed as fold change relative to EP4i-treated Ptger4flox/flox (n = 3 independent experiments). *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 by two-way ANOVA and Tukey's post-test comparing the genotypes within a treatment group. †††p<0.001, ††††p<0.0001 by two-way ANOVA and Sidak's post-test comparing the effects of the treatments within a genotype.",
    "ncbi_link": "Ptger4: 19219"
  },
  {
    "caption": "A, B Jejunal spheroids were cultured in differentiation medium containing 10 µM of Forskolin or an equivalent volume of DMSO. (B) Quantification of the average expression ± s.e.m. of Cldn4 mRNA relative to the DMSO treatment group (n = 3 independent experiments). *p<0.05 compared to DMSO group by unpaired t test.",
    "ncbi_link": "Cldn4: 12740"
  },
  {
    "caption": "E, F Spheroids were cultured in enterocyte medium with the indicated concentrations of CHIR 99021. Quantification of the average expression ± s.e.m. of Cldn4 (E) and Fabp1 (F) mRNAs shown as fold change relative to 0 µM group (n = 3 independent experiments). **p<0.01, ****p<0.0001 as determined by one-way ANOVA and Dunnett's post-test.",
    "ncbi_link": "Cldn4: 12740
Fabp1: 14080"
  },
  {
    "caption": "G Representative images of Ptger4Δ/Δspheroids cultured in differentiation medium with DMSO or 10 µM CHIR 99021 and stained for β-catenin (green) and F-actin (red). Nuclei are visualized with bisbenzimide (blue). Scale bars, 20 µm.",
    "ncbi_link": "Ptger4: 19219"
  },
  {
    "caption": "I, J Spheroids were cultured in enterocyte media, WAE media or WAE media containing 100 pM C59. Quantification of the average expression ± s.e.m. of Cldn4 (I) and Fabp1 (J) mRNAs shown as fold change relative to EP4i group (n = 3 independent experiments). ***p<0.001, ****p<0.0001 as determined by one-way ANOVA and Tukey's post-test.",
    "ncbi_link": "Cldn4: 12740
Fabp1: 14080"
  },
  {
    "caption": "K Quantification of the average expression ± s.e.m. of Axin2 mRNA in spheroids cultured in stem cell or in differentiation medium with the indicated supplements relative to stem (n = 3 independent experiments). ****p<0.0001 compared to stem cell group as determined by one-way ANOVA and Dunnett's post-test.",
    "ncbi_link": "Axin2: 12006"
  },
  {
    "caption": "A Representative whole-mount images of wounds from Ptger4flox/flox (Ptger4fl/fl) and Villin-Cre Ptger4flox/flox (VilCrePtger4fl/fl) mice four days post-biopsy injury. Scale bars, 750 µm. Wounds are outlined with a black dashed line. Asterisk indicates fibrin clot.B, C Quantification of percent healing (1 - [Day 4 wound area/original wound area] x 100) (B) and fibrin clot areas (C) ± s.e.m. (n = 7-8 mice per genotype with 3-4 wounds each, three independent experiments). *p=0.0270, **p=0.0057 by two-tailed unpaired t-test.",
    "ncbi_link": "Cre: 
Ptger4: 19219
Villin: 22349"
  },
  {
    "caption": "Fig. 4. Spironolactone antagonizes ERBB4 phosphorylation both in in vitro and in vivo.(D) Spironolactone reduces phospho-Erbb4 levels in Nrg1-tg mice. Mice were treated with spironolactone for 21 days and sacrificed for western blot analysis. Lysates were probed with indicated antibodies.",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice.(B) Nrg1-tg mice travelled longer distances in the open field arena (effect of genotype F (1,44) =10.53; p=0.0022; 2-way ANOVA). Bonferroni post-hoc analysis revealed a significant genotype-dependent difference between vehicle-treated groups (p=0.0044) but not in spironolactone-treated groups (p=0.3783). Genotype differences were abolished upon spironolactone treatment.",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice.(C) When vehicle treated animal were analyzed in 1 min intervals, transgenic mice showed an increased activity throughout the entire test (effect of genotype F (1,22) =9.27; p=0.0060; 2-way ANOVA), most prominent in intervals 2, 7, and 8 (p=0.0427, p=0.0385 and p=0.000036, respectively, Bonferroni post-hoc test).",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice.(D) There was no significant difference between the genotypes when treated with spironolactone (effect of genotype F (1,22) =2.19; p=0.1535; 2-way ANOVA). However, the interaction of genotype and treatment was significant (F (9,198) =1.94; p=0.0481; 2-way ANOVA).",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice.(E) Nrg1-tg mice treated with spironolactone spent more time in the light compartment during the light-dark test (interaction gene × treatment F (1,41) =4.90; p=0.0324; 2-way ANOVA, and p=0.0219, Bonferroni post-test).",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice. (F) In the Y-maze test, transgenic mice performed less alterations (effect of genotype F (1,44) =11.50; p=0.0015; 2-way ANOVA). The Bonferroni test confirmed this phenotype in vehicle-treated groups (p=0.0011), but not in spironolactone-treated animals (p=0.5950). Spironolactone treatment had a significant effect on the number of alterations (F (1,44) =4.12; p=0.0484; 2-way ANOVA).",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Fig. 5. Chronic spironolactone treatment ameliorates deficits of behavioral endophenotypes in Nrg1-tg mice.(G) Spironolactone treatment significantly enhanced PPI in Nrg1-tg mice (effect of treatment F (1,21) =5.07; p=0.0325; 2-way repeated measures ANOVA). Data are shown as mean, error bars represent SEM. *, p<0.05, **, p<0.01 and ***, p<0.001, Bonferroni test following 2-way ANOVA; Spiro, spironolactone; Veh, vehicle. n=12 per genotype and treatment with an exception of (E) (Nrg1-tg vehicle, n=11; Nrg1-tg Spiro, n=10; wt vehicle, n=12; wt Spiro, n=12) and (G) (Nrg1-tg vehicle, n=11; Nrg1-tg Spiro, n=12; wt vehicle, n=12; wt Spiro, n=12).",
    "ncbi_link": "Nrg1: 211323"
  },
  {
    "caption": "Gata6-WT and Gata6-KOmye peritoneal macrophages (pMɸ) were unstimulated (-) or stimulated with TLR2L Pam3CSK4 (500 ng.ml-1), TLR3L Poly I:C (1 µg.ml-1), TLR4L purified LPS (100 ng.ml-1), TLR5L Flagellin (100 ng.ml-1), TLR7 and 8L R848 (1 µg.ml-1) or TLR9L CpG ODN1826 (5 µM). Culture supernatants were collected 24 h after the start of stimulation and IL-1β and TNF ELISA were performed. n=5, two-way ANOVA analysis with Tukeys multiple comparison post-test.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β (C) and TNF (D) ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated for 24 h with the indicated LPS concentrations. n=3, two-way ANOVA analysis with Sidak's multiple comparison post-test.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β (E) and TNF (F) ELISA from Gata6-WT and Gata6-KOmye pMɸ stimulated with LPS (100 ng.ml-1) for the indicated times. n=3, two-way ANOVA analysis with Sidak's multiple comparison post-test.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated for 18 h with 100 ng.ml-1 LPS or recombinant IL-1 receptor antagonist (rIL-1ra), n=4 to 5, two-way ANOVA analysis with Tukey's multiple comparison post-test.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated for 18 h with 100 ng.ml-1 LPS or 100 ng.ml-1 recombinant TNF (recTNF), n=4 to 5, two-way ANOVA analysis with Tukey's multiple comparison post-test.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Normalised expression of Tlr and Cd14 genes following microarray analysis performed on unstimulated cell-sorted Gata6-WT and Gata6-KOmye pMɸ. Data are shown as mean +/- SEM from three biological replicates. Statistical significance was determined using empirical Bayesian statistic corrected for false discovery rate by the Benjamin-Hochberg procedure. n.d = non detectable.",
    "ncbi_link": "Cd14: 12475
Gata6: 14465"
  },
  {
    "caption": "Mean fluorescence intensity (MFI) of extracellular TLR2, TLR4 and CD14 expression on naïve Gata6-WT and Gata6-KOmye pMɸ. n = 4 to 7 individual mice per group.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Il1b and Tnf mRNA relative expression of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h and 6 h respectively. Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465
Il1b: 16176
Tnf: 21926"
  },
  {
    "caption": "IL-1β Western blot protein analysis (D) of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h and 6 h respectively. Data shown are representative of at least 3 independent experiments. Western blot was performed on whole cell lysates.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Representative dot plot, percentage and mean fluorescence intensity (MFI) analysis of pro-IL-1β+ Gata6-WT and Gata6-KOmye pMФ flow cytometry analysis 3 h after stimulation with 100 ng.ml-1 LPS. n = at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Nlrp3 mRNA relative expression of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h. Data shown are pooled from 3 independent experiments.",
    "ncbi_link": "Gata6: 14465
Nlrp3: 216799"
  },
  {
    "caption": "Western blot protein analysis of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 6 h. Data shown are representative of at least 3 independent experiments. Western blot was performed on whole cell lysates.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of supernatants collected from Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS and either vehicle control (Vh, DMSO) or 10 µM MCC950 for 24 h (n=5). Data shown in (H) are pooled from 5 independent replicates.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Western blot protein analysis (I) of supernatants collected from Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS and either vehicle control (Vh, DMSO) or 10 µM MCC950 for 24 h (n=5).",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Caspase1 (Casp1) mRNA relative expression of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h and 6 h respectively. Data shown are pooled from 3 independent experiments.",
    "ncbi_link": "Casp1: 12362
Caspase1: 12362
Gata6: 14465"
  },
  {
    "caption": "Western blot protein analysis (K) of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h and 6 h respectively. Data shown are pooled from 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS and either vehicle control (Vh, DMSO) or Ac-YVAD-cmk for 24 h. Data shown are pooled of 5 independent replicates.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of Gata6-WT and Gata6-KOmye pMɸ stimulated with 100 ng.ml-1 LPS for 3 h, followed by a 30 min pulse with either vehicle control (Vh), 5 mM ATP or 20 µM Nigericin. Data shown are pooled of 5 independent replicates.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Representative picture of confocal immunofluorescence analysis of Gata6-WT and Gata6-KOmye pMФ stimulated with 100 ng.ml-1 LPS for 3 h, followed by a 30 min pulse with 5 mM ATP. The white arrows show ASC specks. Scale bar = 10 µm.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA analysis of supernatants of Gata6-WT and Gata6-KOmye pMɸ in monoculture or co-cultured (ratio 1:1) and stimulated for 24 h with 100 ng.ml-1 LPS. Data shown are pooled from 3 independent experiments. One-way ANOVA statistical analysis with Tukey's multiple comparison test was performed.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA analysis of supernatants of Gata6-WT and Gata6-KOmye pMɸ co-cultured in the same well (co-culture) or using Transwell system (ratio 1:1) and stimulated for 24 h with 100 ng.ml-1 LPS. Data shown are pooled from 3 independent experiments. One-way ANOVA statistical analysis with Tukey's multiple comparison test was performed.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Microarray analysis of Ptgis, Tbxas1, Ptges2 and Ptgs1 expression from Gata6-WT and Gata6-KOmye pMɸ isolated from naïve mice. Data is shown as mean +/- SEM from three biological replicates. Statistical significance was determined using empirical Bayesian statistic corrected for false discovery rate by the Benjamin-Hochberg procedure.",
    "ncbi_link": "Gata6: 14465
Ptges2: 96979
Ptgis: 19223
Ptgs1: 19224
Tbxas1: 21391"
  },
  {
    "caption": "Western blot analysis of Ptgis protein level of unstimulated pMФ from Gata6-WT and Gata6-KOmye mice.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Mass spectrometry analysis of 6-keto-PGF1α, TXB2 and PGE2 content of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated for 3 h with 100 ng.ml-1 LPS. n = 6. Two-way ANOVA statistical analysis with Tukey's multiple comparison post-test was performed.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-10 ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS. Data shown are representative of at least 5 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-10 (B) and IL-1β (C) ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, beraprost (1 and 10 µM), cicaprost (1 and 10 µM), Iloprost (1 or 10 nM) or vehicle control (Vh, DMSO). Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-10 (D) and IL-1β (E) ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 µM beraprost, 10 µM PGE2, 10 µM U46619, 100 µM picotamide or vehicle control (Vh, methyl acetate). Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 ng.ml-1 IL-10, 10 µM beraprost or vehicle control (Vh). Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 µM beraprost, 5 µg.ml-1 αIL-10R or isotype antibody. Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β (H) and IL-10 (I) ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 µM MCC950, 5 µg.ml-1 αIL-10R or isotype antibody All stimulations were performed for 16 h. Data shown are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 10 ng.ml-1 IL-10 and 5 mM ATP. Data shown are a pool of 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Flow cytometry analysis of Mitotracker (MT) Green and Red integration in Gata6-WT and Gata6-KOmye naïve pMɸ (gated on F4/80hi/+ Tim4+) in vivo, 30 min after intraperitoneal injection (i.p.) of 1 µM of Mitotracker Green and Red. Data shown are representative of 3 to 5 independent mice of each genotype and are expressed as mean +/- SEM. Student's t test analysis was performed.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Flow cytometry analysis of Mitotracker green and red staining in Gata6-WT and Gata6-KOmye pMɸ (gated on F4/80hi/+ Tim4+) unstimulated (-) or after LPS (100 ng.ml-1), IL-10 (10 ng.ml-1), αIL-10R (5 µg.ml-1) or isotype (5 µg.ml-1) stimulation for 16 h in vitro. Data shown are pooled from 3 independent experiments and normalized to WT unstimulated.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Flow cytometry analysis of MitoSOX staining in Gata6-WT and Gata6-KOmye pMɸ (gated on F4/80hi/+ Tim4+) unstimulated (-) or after LPS (100 ng.ml-1), IL-10 (10 ng.ml-1) and αIL-10R (5 µg.ml-1) stimulation for 16 h in vitro. Data shown are pooled from 2 independent experiments and normalized to WT unstimulated.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "IL-1β ELISA of supernatants of Gata6-WT and Gata6-KOmye pMɸ unstimulated (-) or stimulated with 100 ng.ml-1 LPS, 500 µM MitoTempo, 10 mM NAC, 0.5 µM MitoQ for 16 h. Data are representative of at least 3 experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "mRNA expression analysis of Il1b, Nlrp3 and Caspase1 (Casp1) of Gata6-WT and Gata6-KOmye pMФ stimulated for 3 h with 100 ng.ml-1 LPS, 10 µM beraprost, 10 ng.ml-1 IL-10, 5 µg.ml-1 αIL-10R or 5 µg.ml-1 isotype. Data are representative of at least 3 independent experiments.",
    "ncbi_link": "Casp1: 12362
Caspase1: 12362
Gata6: 14465
Il1b: 16176
Nlrp3: 216799"
  },
  {
    "caption": "Western blot analysis (left) and quantification (right) of Gata6-WT and Gata6-KOmye pMФ stimulated for 6 h with 100 ng.ml-1 LPS, 10 µM beraprost, 10 ng.ml-1 IL-10 or 5 µg.ml-1 αIL-10R. Data are representative of 3 independent experiments.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Caspase1 activity analysis of Gata6-WT and Gata6-KOmye pMФ stimulated for 16 h with 100 ng.ml-1 LPS, 10 µM beraprost, 10 ng.ml-1 IL-10, 5 µg.ml-1 αIL-10R or 5 µg.ml-1 isotype. n = 5 to 8 individual mice.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Mean fluorescence intensity (MFI) of pro-IL-1β of Gata6-WT and Gata6-KOmye pMФ stimulated for 3 h with 100 ng.ml-1 LPS, 10 µM beraprost, 10 ng.ml-1 IL-10, 5 µg.ml-1 αIL-10R or 5 µg.ml-1 isotype for 16 h or freshly isolated. n = 6 to 13 individual mice. Data were log transformed before performing statistical analysis.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "mRNA expression analysis of Il10 and Tnf of Gata6-WT and Gata6-KOmye pMФ stimulated for 3 h with 100 ng.ml-1 LPS, 10 µM beraprost, 10 ng.ml-1 IL-10 or 5 µg.ml-1 αIL-10R. Data are representative of at least 3 independent experiments.",
    "ncbi_link": "Gata6: 14465
Il10: 16153
Tnf: 21926"
  },
  {
    "caption": "D, Dnmt3a/b-KO did not affect NPC proliferation. Depicted are data points for every sample with genotype means ± standard errors of the mean (SEM). E, Reduced percentage of dead cells (Annexin V/propidium iodide (PI) double-positive) in KO cultures at 46 h after start of differentiation. Depicted are data points for every sample with genotype means ± SEM. ",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "H, Dnmt3a/b-dependent loss of DNA methylation at neuronal gene candidates was associated with reduced transcription in neurons. Depicted are mean CpG methylation levels at specified genomic regions as determined by RRBS (left) and expression fold changes in KO versus WT neurons as determined by qRT-PCR (right; n = 4 cultures per genotype; p-values from Mann-Whitney test; depicted are data points for every sample with genotype means ± SEM).",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "A, No difference in numbers of Ki67-positive, proliferating cells was observed between the subgranular zone (SGZ) of Dnmt3a/b-WT and Dnmt3a/b-KO mice one week after tamoxifen administration. Depicted are data points for every animal with genotype means ± SEM. B, Bright field image of Ki67-positive cells stained using diaminobenzidine method. Scale bar: 100 µm. ",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "C, KO of Dnmt3a/b did not affect numbers of new-born neurons in the dentate gyrus. Mice were administered with tamoxifen and analyzed 5 weeks after the first injection. BrdU was injected 3.5 weeks before analysis. Depicted are data points for every animal with genotype means ± SEM. D, Fluorescence image of BrdU/NeuN-positive new-born neurons. Scale bar: 25 µm. ",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "A-B, Quantification of adult-born (BrdU-positive) cells in the dentage gyrus (DG) of Dnmt3a/b-KO and WT mice after five weeks or three months of environmental enrichment (ENR) or standard housing (STD). BrdU was injected 4.5 weeks before analysis. Depicted p-values correspond to genotype effects from two-way ANOVA. Influences of ENR were significant with p < 0.01. Depicted are data points for every animal with group means ± SEM.",
    "ncbi_link": "Dnmt3a: 13435"
  },
  {
    "caption": "A Agarose gel image illustrating PCR amplicons of ltaS (LBA0447), slpB, and slpX deletions in NCK2187.",
    "ncbi_link": "ltaS: 
slpB: 3252692
slpX: 3253051"
  },
  {
    "caption": "B SDS-PAGE gel of 5 M LiCl‐purified S‐layer fractions from the parental strains, NCK56 and NCK1909, NCK2030 (LTA+, SlpA+, SlpB−, SlpX−), and NCK2187 (LTA−, SlpA+, SlpB−, SlpX−).",
    "ncbi_link": "LTA: 
SlpA: 3252774
SlpB: 3252692
SlpX: 3253051"
  },
  {
    "caption": "A B6 Rag1−/−mice were injected with 106CD4+CD45RBhiT cells and then orally gavaged with NCK56 (red), NCK2187 (green), or SlpA (blue), 1 and 3 days after transfer, and subsequently once a week for four consecutive weeks, or left untreated (magenta). A group of mice was co‐transferred with CD4+CD25+T cells as a positive control for protection (Tregs; gray). Colitis severity was determined in part by weight loss, diarrhea scores, and FOB. See Supplementary Tables S1, S2 and S3 for statistical analyses results.",
    "ncbi_link": "Rag1: 19373
SlpA: 3252774"
  },
  {
    "caption": "Colitis was induced in B6 Rag1−/−mice as described in Fig .A, B Colonic expression of tight junction‐associated genes Cldn3 and Ocln, determined by RT-PCR relative to 18S rRNA (A), were used as measures of epithelial barrier integrity. Sham adoptive transferred B6 Rag1−/−mice (white bars) were used as baseline controls in some cases. n = 5 mice/group. Data represent three individual experiments and are shown as mean ± SEM. *P 0.05, **P 0.01. Black asterisks compare NCK2187 to PBS‐treated adoptively transferred mice, and red asterisks to NCK56‐treated mice.",
    "ncbi_link": "18S: 
Cldn3: 12739
Ocln: 18260
Rag1: 19373"
  },
  {
    "caption": "Colitis was induced in B6 Rag1−/−mice as described in Fig .A, B Passive transepithelial absorption of FITC‐dextran (B), was used as measures of epithelial barrier integrity. Sham adoptive transferred B6 Rag1−/−mice (white bars) were used as baseline controls in some cases. n = 5 mice/group. Data represent three individual experiments and are shown as mean ± SEM. *P 0.05, **P 0.01. Black asterisks compare NCK2187 to PBS‐treated adoptively transferred mice, and red asterisks to NCK56‐treated mice.",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "C Binding of SlpA to SIGNR3, but not SIGNR1 expressed by CHO‐S cells. Gray tinted line = untransfected CHO‐S cells; blue = untransfected CHO‐S cells + labeled SlpA; green = SIGNR1‐transfected CHO‐S cells + labeled SlpA; red = SIGNR3‐transfected CHO‐S cells + labeled SlpA. Binding assays in CHO‐S cells were performed three individual times.",
    "ncbi_link": "SIGNR1: 170786
SIGNR3: 170779"
  },
  {
    "caption": "E Binding of SlpA to DC‐SIGN expressed by CHO‐S cells. Gray tinted line = untransfected CHO‐S cells; blue = untransfected CHO‐S cells + labeled SlpA; red = DC‐SIGN‐transfected CHO‐S cells + labeled SlpA. Binding assays in CHO‐S cells were performed three individual times.",
    "ncbi_link": "DC‐SIGN: 30835"
  },
  {
    "caption": "F, G IL‐1β production by colonic DCs of naïve WT B6 GF or B6 Signr3−/− (KO) mice treated with NCK56 (blue) or NCK2187 (green) four times, or left untreated (black), as determined by flow cytometry. n = 5 mice/group. Data represent four individual experiments and are shown as mean ± SEM. *P 0.05. Black asterisks compare NCK2187 to untreated (PBS) mice, and red asterisks to NCK56‐treated mice.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "WT B6 or B6 Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −3 and −1, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times and monitored for disease progression.A Colitis severity was determined in part by weight loss. n = 5 mice/group.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "WT B6 or B6 Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −3 and −1, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times and monitored for disease progression.B, C Colitis scores based on histopathology and gross morphology of the colons were also used as measures of disease. Scale bar = 50 μm. n = 5 mice/group. Empty bars = WT; lined bars = KO; white bars = untreated; purple bars = DSS; red bars = DSS + NCK56; green bars = DSS + NCK2187; blue bars = DSS + SlpA.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "WT B6 or B6 Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −3 and −1, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times and monitored for disease progression.D Colonoscopies were performed in the different groups with a Multi‐Purpose Rigid™ Telescope attached to a TELE PACK X on day 10.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "WT B6 or B6 Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −3 and −1, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times and monitored for disease progression.E Mean relative colonic expression of tight junction‐associated genes in WT mice. n = 5 mice/group.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "WT B6 or B6 Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −3 and −1, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times and monitored for disease progression.F Fecalalbumin levels in WT mice as a measure of intestinal permeability. n = 5 mice/group.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "Signr3+/+ (WT) or Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −1 and −3, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times, and immunity was analyzed by flow cytometry at day 10.A Representative plots indicate the frequency of neutrophils in the colons of untreated or DSS‐treated WT (left) and KO mice (right). Empty bars = WT; lined bars = KO; white bars = untreated; purple bars = DSS; red bars = DSS + NCK56; green bars = DSS + NCK2187; blue bars = DSS + SlpA.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "Signr3+/+ (WT) or Signr3−/− (KO) mice were orally gavaged with NCK56, NCK2187, or SlpA on days −1 and −3, and 3% DSS was given in the drinking water. Mice were gavaged with bacteria or purified SlpA every other day for an additional three times, and immunity was analyzed by flow cytometry at day 10.B, C Colonic DCs and macrophages (MΦs) were analyzed by flow cytometry for the production of IL‐1β (B), and colonic FoxP3+ Tregs were evaluated for co‐expression of RORγt+ (C). n = 5 mice/group. Gray tinted line = isotype control; black = untreated; purple = DSS; red = DSS + NCK56; green = DSS + NCK2187; blue = DSS + SlpA.",
    "ncbi_link": "Signr3: 170779"
  },
  {
    "caption": "(G, H) Jacob shRNA knockdown prevents Aβ-induced CREB shutoff. (G) Representative confocal images of hippocampal neurons transfected with Jacob-shRNA or scrambled (scr) shRNA control (both expressing GFP) and treated with oligomeric preparations of Aβ1-42 or Aβ3(pE)-42. (H) Neurons transfected with a Jacob knockdown construct did not display reduction of pCREB immunofluorescence intensity after treatment with Aβ1-42 or Aβ3(pE)-42. Bar plot of mean nuclear pCREB intensity normalized to untreated control. Scale bar: 10 µm. N=29-39 nuclei from 2 independent experiments.",
    "ncbi_link": "GFP: 
Jacob: 56876"
  },
  {
    "caption": "(P) Double transgenic TBA2.1 Jacob/Nsmf knockout (TBA2.1, -/-) mice display significantly lower neuronal loss compared to TBA2.1 mice. The number of NeuN positive cells was normalized to WT group. N=36-47 CA1 images analyzed from 10-12 animals per genotype. Dotted line marks value of the normalized control group -100%. (Q) Jacob knockout rescues decrease in the BdnfIV gene transcription. Bar plot of mean BdnfIV transcript levels in hippocampal homogenates normalized to β-actin as reference transcript. N=5-10 hippocampi.",
    "ncbi_link": "β-actin: 11461
BdnfIV: 12064
Nsmf: 56876
Jacob: 56876"
  },
  {
    "caption": "(C) The C-terminus (CREB-166-341-tagRFP) but not the N-terminus (CREB-1-165-tagRFP) of CREB closely associates with Jacob-GFP in FRET saturation experiments. (D) Both the N- (Jacob-1-228-GFP) and the C-terminus (Jacob-262-532-GFP) of Jacob are in close proximity to CREB-tagRFP, however, the Jacob-1-228-GFP association with CREB is significantly stronger. FRET efficiency is presented in arbitrary units from 5-6 independent experiments.",
    "ncbi_link": "GFP: 
RFP: 
CREB: 1385
Jacob: 56876"
  },
  {
    "caption": "(M) Co-immunoprecipitation experiments to map the binding region of Jacob to the LIM1 domain of LMO4 revealed the association with Jacob-179-246-GFP, but not with Jacob-45-172-GFP (CREB-binding region).",
    "ncbi_link": "GFP: 
Jacob: 56876"
  },
  {
    "caption": "A Jacob-LMO4-binding mutant expressed in the nucleus does not induce CREB shutoff. Representative confocal images of hippocampal neurons transfected with ΔMyr-Jacob-GFP (Jacob targeted to the nucleus) or ΔMyr-Jacob-L175A-V176A-GFP. Scale bar: 10 µm. Lookup table indicates the pixel intensities from 0 to 255. (R, T) The mean of nuclear (T) CREB immunoreactivity in Jacob-expressing neurons was normalized to non-transfected controls. N =23-33 neuronal nuclei from two independent cell cultures.",
    "ncbi_link": "GFP: 
Jacob: 56876"
  },
  {
    "caption": "(B, C) FRET saturation experiments with (B) LMO4-GFP and CREB-1-165-tagRFP or (C) CREB-166-341-tagRFP and CREB-GFP and LIM1-1-80-tagRFP or LIM2-81-165-tagRFP revealed an association between the LIM1 domain of LMO4 and the C-terminus of CREB. N=8 independent experiments.",
    "ncbi_link": "RFP: 
CREB: 1385"
  },
  {
    "caption": "(H-K) Knockdown of LMO4 reduces nuclear pCREB immunoreactivity. (H, J) Representative confocal images of hippocampal neurons transfected with LMO4 shRNA construct or scrambled control (both expressing GFP under CMV promoter as a transfection control). Scale bar: 10µm. Dot plots representing the mean of nuclear (I) pCREB or (K) CREB staining intensity normalized to scrambled control. N=30-37 nuclei analyzed from at least 3 independent cell cultures.",
    "ncbi_link": "GFP: 
LMO4: 16911"
  },
  {
    "caption": "(B) Mapping of the mCherry-PP1γ interaction region within the Jacob sequence revealed binding of a C-terminal fragment (Jacob-310-250-GFP) as well as the N-terminal part (Jacob-173-246-GFP) where the region between 213-246 aa is sufficient for immunoprecipitation. The pink boxes in the schematic indicate binding regions.",
    "ncbi_link": "GFP: 
Jacob: 56876"
  },
  {
    "caption": "Treatment of hippocampal primary neurons expressing phosphodeficient Jacob in the nucleus with OA rescues Jacob-induced CREB shutoff. Confocal images of pCREB immunostaining in DIV15 neurons overexpressing ΔMyr-Jacob-S180A-GFP with and without OA treatment. Scale bar: 20 μm. Lookup table indicates the pixel intensities from 0 to 255. N=14-17 nuclei analyzed from two independent cell cultures.",
    "ncbi_link": "GFP: 
Jacob: 56876"
  },
  {
    "caption": "(K) Treatment with staurosporine decreases Jacob phosphorylation level (S180), but increases its association with LMO4-tagRFP. Immunoblot of HEK293T cells extracts transfected with LMO4-tagRFP and ΔMyr-Jacob-GFP or GFP alone. (L) Treatment with staurosporine decreases the association of Jacob with CREB. Immunoblot of HEK293T cells extract transfected with CREB-tagRFP and ΔMyr-Jacob-GFP or GFP as a control. (",
    "ncbi_link": "GFP: 
RFP: 
CREB: 1385
LMO4: 16911
Jacob: 56876"
  },
  {
    "caption": "A. Glucose transporter1 (Glut1) immunohistochemistry on sections of 5 weeks growth glioma in ROSAmT/mG::Pdgfb-iCre mouse (50 µm depth stack). Hypoxic tumor cells upregulate Glut1.",
    "ncbi_link": "ROSA: 
Pdgfb: 18591"
  },
  {
    "caption": "B. Still image of two-photon live imaging on 2 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse demonstrating tip cell filopodia extension indicative of sprouting. See Supplementary movie 1.",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "C. Representative images of two-photon live imaging of the same glioma area of the same mouse on 2 and 5 weeks growth glioma (BFP positive) implanted in ROSAmT/mG::Pdgfb-iCre mouse (350µm depth stack). Note differences in network complexity and vessel diameter.",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "F. Two-photon live imaging of vessel perfusion using FITC-dextran IV injection in ROSAmT/mG mice (300µm depth stack).",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "A. F4/80 immunohistochemistry on a section of 5 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse (50µm depth stack).",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "B. Two-photon live imaging of LifeAct-GFP bone marrow transplantation in 5 weeks implanted glioma in ROSAmT/mG mice (100µm depth stack).B lower panels: 280µm;",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "A. MHCII and MRC1 immunohistochemistry on a section of 3-5 weeks growth glioma implanted in ROSAmT/mG::Pdgfb-iCre mouse. M1 macrophages, preferentially located in hypoxic area, are abundant at 3 weeks and their number decreases at 5 weeks. M2 macrophages, preferentially located around blood vessels, are present at a low level at 3 weeks and their number increases at 5 weeks.Scale bars: A: 200µm;",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "E. MRC1 immunohistochemistry on 3 weeks growth glioma in ROSAmTmG::Pdgfb-iCre mouse following MHCII-FITC labeled IV injection at 6 or 24h (5µm depth stack). Note the segregation of MRC1 and MHCII cell labeling at 6 hours and the overlapping of these two markers at 24 hours (n=5 mice per group). Statistical analysis: E. t-test. Error bars: E: 50µm.",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "A. Glut1 immunohistochemistry on sections of 4 weeks growth glioma in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Anti-CSF1 antibody treatment induces a two-fold decrease in vessel caliber compared to control antibody (n=6 mice per group) (50µm depth stack). Statistical analysis: A.F. t-test; Error bars: A-C-F: meanSD; Scale bars: A-B-E: 150µm.",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "B. Glut1 and MRC1 immunohistochemistry on 4 weeks growth glioma in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Anti-CSF1 antibody induces a decrease in macrophage recruitment in the tumor microenvironment associated with an improved blood brain barrier functionality assessed by a better Glut1 blood vessel coverage compared to control antibody treated mice (50µm depth stack). Scale bars: A-B-E: 150µm.",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "E. Two-photon live imaging of vessel perfusion in 4 weeks implanted glioma growth using FITC-dextran IV injection in ROSAmT/mG mice treated with anti-CSF1 or control antibodies. Scale bars: A-B-E: 150µm.",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "A. MRC1 immunohistochemistry on sections of 3 weeks growth glioma in ROSAmT/mG mice treated with recombinant CSF1 or carrier. Recombinant CSF1 treatment induces blood vessel enlargement in early tumors (50µm depth stack).",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "A. qPCR analysis of CCR7, IL12, CCL19, CXCL10, MRC1, TGFβ, CD209 and VEGF on RNA samples from MHCII or MRC1 tumor extracted macrophages (n=5 isolation per group).Statistical analysis: A. G. Mann-Whitney u-test. Error bars: A-D-E-F: meanSD",
    "ncbi_link": "CD209: 
IL12: 
TGFβ: 
CCL19: 24047
CCR7: 12775
CXCL10: 15945
MRC1: 17533
VEGF: 22339"
  },
  {
    "caption": "B. sFlt1 binding assay on 5 weeks growth glioma section implanted in ROSAmT/mG::Pdgfb-iCre mouse. At late stage tumor growth, M2 macrophages surrounding blood vessels present very high amount of VEGF (binding sFlt1) to the neighboring endothelial cells (5µm depth stack).",
    "ncbi_link": "ROSA: 14910
Pdgfb: 18591"
  },
  {
    "caption": "C. F4/80 immunohistochemistry and sFlt1 binding on sections of 4 weeks growth glioma in Vegfafl/fl::LysMCre+ or Vegfafl/fl ::LysMCre- mice (50µm depth stack).",
    "ncbi_link": "LysM: 
LysM: 217779///75099///70082///80289
Vegfa: 22339"
  },
  {
    "caption": "D. Quantification of F4/80 positive macrophages. VEGF depletion in myeloid cells does not alter macrophages recruitment (n=7 mice per group). Statistical analysis: D.E.F. t-test; Error bars: A-D-E-F: meanSD;",
    "ncbi_link": "VEGF: 22339"
  },
  {
    "caption": "E. Quantification of F4/80 positive macrophages binding sFlt1. VEGF depletion is effective in 61% of the macrophages invading the tumor (n=7 mice per group). Statistical analysis: D.E.F. t-test; Error bars: A-D-E-F: meanSD;",
    "ncbi_link": "VEGF: 22339"
  },
  {
    "caption": "F. Vessel diameter quantification. Myeloid cell derived VEGF depletion induces blood vessel "normalization" compared to control (n=7 mice per group). Statistical analysis: D.E.F. t-test; Error bars: A-D-E-F: meanSD;",
    "ncbi_link": "VEGF: 22339"
  },
  {
    "caption": "G. Tumor volume quantification in 4 weeks growth glioma in Vegfafl/fl::LysMCre+or Vegfafl/fl::LysMCre- mice (n=7 mice per group). Statistical analysis: G. Mann-Whitney u-test. Error bars: G: median interquartile. Scale bars: 100µm.",
    "ncbi_link": "LysM: 217779///75099///70082///80289
Vegfa: 22339"
  },
  {
    "caption": "A-L Wild type cultured in C- (A), cho2opi3 cultured in C+ (B ), coS#4 (C-D), coS#3 (E-G), and coS#2 (I-K) cultured in C- were analyzed by  electron microscopy. In addition, coS#3 (H) and coS#2 (L) are shown after culture in C+ for 3 generations. The arrow heads (F, I, J) point to protrusions in the  nuclear envelope. CW, cell wall; ER, endoplasmic reticulum; PM, plasma membrane; M, mitochondria; N, nucleus; V, vacuole; *,  lipid  droplet. Scale bars correspond to 200 nm (A, B, D, F, G) or 500 nm (C, E, H, I, J, K, L).",
    "ncbi_link": "cho2: 853061
opi3: 853536"
  },
  {
    "caption": "Membrane lipid and TAG content, and ergosterolester content (EE, inset) per OD600 unit of the yeast  strains indicated after culture to mid-log phase  in SD with or without 1 mM  choline (C); * p < 0.05, ** p < 0.01, unpaired two-tailed t-test of the indicated bar compared to the C+ condition. Data information: All data were obtained by mass spectrometry and are presented as mean ±SD (n=3 biological replicates); * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, unpaired two-tailed t-test of the indicated bar compared to the  cho2opi3 parent unless indicated otherwise.",
    "ncbi_link": "cho2: 853061
opi3: 853536"
  },
  {
    "caption": "Generation of suppressors of choline auxotrophy of  cho2opi3, cho2opi3lro1, and cho2opi3lro1 pLRO1 on choline-free medium as indicated at 30 oC for 7 d.",
    "ncbi_link": "cho2: 853061
lro1: 855742
LRO1: 855742
opi3: 853536"
  },
  {
    "caption": "Growth (30 oC for 6 d) and phospholipid composition of co acc1N/H lro1  pLRO1  cultured in SD C- ura-, containing glucose/galactose mixtures (2%, w/v) as carbon source with the percentage of galactose indicated. Phospholipid composition analyzed by TLC is presented as mean percentage of total phospholipid of 3 biological replicates with the individual values indicated.",
    "ncbi_link": "acc1: 855750
lro1: 855742
LRO1: 855742"
  },
  {
    "caption": "ACC1 transcript levels after switching the strains indicated from SD C+I+ to the medium indicated at OD600 0.02 or 0.2 (co diploid in C-), and culture for 24 h at 30 oC. Data were normalized to ACT1  and expressed as means of 3 biological replicates relative to the corresponding strain cultured in C+I+, with the individual values indicated.",
    "ncbi_link": "ACC1: 855750
ACT1: 850504"
  },
  {
    "caption": "(F-G) EM  analysis of cho2opi3 cells that after preculture in SD C+, were transferred to OD600 0.05 and subsequently cultured to  mid-log phase  in SD C+ (F) or SD C- (G) both containing 0.05 μg/mL SorA. CW, cell wall; ER, endoplasmic reticulum; M, mitochondria; N, nucleus; V, vacuole; *, lipid droplet. Scale bars correspond to 500 nm.",
    "ncbi_link": "cho2: 853061
opi3: 853536"
  },
  {
    "caption": "POX1  transcript levels after switching the strains indicated from SD C+I+ to the medium indicated at OD600 0.02 or 0.2 (co diploid in C-), and culture for 24 h at 30 oC. Data were normalized to ACT1  and expressed as means of 3 biological replicates relative to the corresponding strain cultured in C+I+, with the individual values indicated.",
    "ncbi_link": "ACT1: 850504
POX1: 852667"
  },
  {
    "caption": "Growth  of co S(2n-1) in the absence of choline is lost when GPT2 or DGA1  is overexpressed, and restored by SorA. Plasmids pHEYg-1-DGA1, pHEYg-1-GPT2 and the empty vector control (pEV) were transformed into the strains indicated. After preculture in SD C+, ten-fold serial dilutions were spotted on SD C+/- with or without 0.1 μg/mL  SorA  and incubated at 30 oC for 3 d.",
    "ncbi_link": "DGA1: 854419
GPT2: 853941"
  },
  {
    "caption": "Intensity encoded GP-images of the indicated C-Laurdan-stained yeast strains cultured with or without choline, accompanied by the corresponding intensity weighted GP-histogram fitted to a single Gaussian function (light blue line), and transmission image. White arrows point to  plasma membranes exhibiting higher lipid packing than internal, organellar membranes; blue horizontal arrows indicate highly packed lipid  material in co S(2n-1). To deplete the cho2opi3 parent of PC, cells were transferred to SD C- at OD600 0.1, and cultured into mid-log phase. White scale bars correspond to 10 µm; red scale bars in transmission images correspond to 5 µm.",
    "ncbi_link": "cho2: 853061
opi3: 853536"
  },
  {
    "caption": "C. Representative image of Syt antibody uptake at axons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector or VAPA/B shRNAs. Yellow and grey arrowheads mark presynaptic boutons with and without internalized Syt, respectively. Zooms represent typical boutons. Scale bars: 5 µm (full size) and 2 µm (zoom).",
    "ncbi_link": "VAPA: 58857"
  },
  {
    "caption": "D. Quantifications of fluorescence intensity of internalized endogenous Syt (B, C) at single presynaptic boutons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector or VAPA/B shRNAs. N=2, n=288-541 boutons. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "VAPA: 58857"
  },
  {
    "caption": "J. Representative image of Syt antibody uptake at axons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector, SCRN1 shRNA or SCRN1 shRNA with GFP-SCRN1. Yellow and grey arrowheads mark presynaptic boutons with and without internalized Syt, respectively. Zooms represent typical boutons. Scale bars: 5 µm (full size) and 2 µm (zoom).",
    "ncbi_link": "SCRN1: 502776"
  },
  {
    "caption": "K. Quantifications of fluorescence intensity of internalized endogenous Syt (B, C) at single presynaptic boutons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector, SCRN1 shRNA alone or SCRN1 shRNA with GFP-SCRN1. N=2, n=201-300 boutons. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "SCRN1: 502776"
  },
  {
    "caption": "B. Live hippocampal neurons (DIV17-18) co-expressing TagRFP-ER with GFP, GFP-SCRN1, GFP-SCRN1-F402A, SCRN1 shRNA or VAPA/B shRNAs. Scale bars: 5 µm (full size) and 2 µm (zoom).",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "C. Time-lapse of TagRFP-ER dynamics in hippocampal neurons (DIV16-18) co-expressing GFP, GFP-SCRN1, GFP-SCRN1-F402A, SCRN1 shRNA or VAPA/B shRNAs. Intact ER structures (dark arrowheads), intact and dynamic ER structures (light arrowheads) and impaired an non-dynamic ER structures (arrows) are indicated. Scale bars: 5 µm (full size) and 2 µm (zoom).",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "E. ER nanostructures visualized with GFP-Sec61β in axons of hippocampal neurons (DIV18) immunostained for α-Tubulin and co-expressed with pSuper empty vector, SCRN1 shRNA or VAPA/B shRNAs, and subjected to expansion microscopy. Scale bars: 2 µm (full size) and 500 nm (zoom).",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "I. Average normalized fluorescent TagRFP-ER recovery after photo-bleaching in hippocampal neurons (DIV18) co-expressing pSuper empty vector, SCRN1 shRNA, VAPA/B shRNAs. N=4, n=6-12 neurons. J. Normalized fluorescent TagRFP-ER recovery after photo-bleaching at T=60 sec in hippocampal neurons (DIV18) co-expressing pSuper empty vector, SCRN1 shRNA, VAPA/B shRNAs. N=4, n=6-12 neurons. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "A. Representative image of Syt antibody uptake at axons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector, SCRN1 shRNA or SCRN1 shRNA with GFP-SCRN1-F402A. Yellow and grey arrowheads mark presynaptic boutons with and without internalized Syt, respectively. Zooms represent typical boutons. Scale bars: 5 µm (full size) and 2 µm (zoom). B. Quantifications of fluorescence intensity of internalized endogenous Syt at individual presynaptic boutons of hippocampal neurons (DIV18) co-expressing RFP and pSuper empty vector, SCRN1 shRNA or SCRN1 shRNA with GFP-SCRN1-F402A. N=2, n=201-300 boutons. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "SCRN1: 502776"
  },
  {
    "caption": "D. Time-lapses of cytosolic GCaMP6f upon electric field stimulation (50 APs, 20 Hz) in axons of hippocampal neurons (DIV21) co-expressing pSuper control, SCRN1 shRNA or VAPA/B shRNAs. Arrowheads mark presynaptic boutons. Scale bar: 5 µm.",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "E. Average normalized response of GCaMP6f fluorescent intensity at presynaptic boutons upon stimulation (50 APs, 20 Hz) in hippocampal neurons (DIV21) co-expressing pSuper empty vector, SCRN1 shRNA or VAPA/B shRNAs. N=5-6, n=15-27. F. Average normalized peak response of GCaMP6f at presynaptic boutons upon stimulation (50 APs, 20 Hz) in hippocampal neurons (DIV21) co-expressing pSuper empty vector, SCRN1 shRNA or VAPA/B shRNAs. N=5-6, n=15-27. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "SCRN1: 502776
VAPA: 58857"
  },
  {
    "caption": "G. Representative time-lapse of cytosolic GCaMP6f before (F0) and after (Fmax) ionomycin treatment at axons of hippocampal neurons (DIV18) co-expressed with mRFP and pSuper empty vector or VAPA/B shRNAs. Arrowheads mark presynaptic boutons. Scale bar: 5 µm.",
    "ncbi_link": "VAPA: 58857"
  },
  {
    "caption": "H. Basal GCaMP6f fluorescence (F) normalized to the maximum GCaMP6f fluorescence (Fmax) after ionomycin treatment at presynaptic boutons of hippocampal neurons (DIV18) co-expressing mRFP with pSuper empty vector or VAPA/B shRNAs. N=2, n=47-50. I. Average basal GCaMP6f fluorescence (F0) normalized to the max GCaMP6f fluorescence intensity (Fmax) after ionomycin treatment at presynaptic boutons of hippocampal neurons (DIV18) co-expressing mRFP with pSuper empty vector or VAPA/B shRNAs. N=2, n=47-50. Data information: Data represent Mean ± SEM; NS: not significant; *P < 0.05; **P < 0.01; ***P < 0.001, by Mann-Whitney U test.",
    "ncbi_link": "VAPA: 58857"
  },
  {
    "caption": "(A) HeLa cells expressing GFP‐tagged UBQLN1 or UBQLN2 (or GFP for controls) were transferred to starvation medium (PBS) for the indicated time. Where specified, only serum was removed from the culture medium. Viability of transfected cells was assessed by PI staining and analysed by flow cytometry. The graph represents the mean of three experiments±s.e.",
    "ncbi_link": "UBQLN1: 29979
UBQLN2: 29978"
  },
  {
    "caption": "(B) HeLa cells were depleted of UBQLN1 or UBQLN2 by siRNA transfection; depletion was verified by Western blot. Cells were starved for increasing periods of time, and their viability was analysed as in (A). The graph represents the mean of three experiments±s.e; *P0.05 between control and UBQLN2‐KD at 6 h (paired Student's t‐test). GAPDH, glyceraldehyde‐3‐phosphate dehydrogenase; GFP, green fluorescent protein; KD, knockdown; PI, propidium iodide; siRNA, short interfering RNA; UBQLN, ubiquilin.",
    "ncbi_link": "UBQLN1: 29979
UBQLN2: 29978"
  },
  {
    "caption": "(A) HeLa cells were transfected with siRNAs for autophagy-related gene ATG5 (siATG5) or with a non-silencing siRNA (siC). Depletion of ATG5, which decreased the levels of the ATG5-ATG12 covalent complex, was confirmed by Western blot. Loading control: transferrin receptor (TfR).",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(B) Control or ATG5‐KD cells transfected with UBQLN1 were starved, and the cell viability was assessed as in Fig 1; the graph represents the mean of three experiments±s.e.",
    "ncbi_link": "ATG5: 9474
UBQLN1: 29979"
  },
  {
    "caption": "(C) HeLa cells were stably transfected with control (shC) or ATG7 (shATG7) shRNA; depletion was verified by Western blot (loading control: GAPDH).",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(D) Control or ATG7‐KD cells transfected with UBQLN1 were starved for 3 or 6 h and assessed for their viability. The graph represents the mean of three experiments±s.e. GAPDH, glyceraldehyde‐3‐phosphate dehydrogenase; KD, knockdown; Pl, propidium iodide; shRNA, short hairpin RNA; siRNA, short interfering RNA; UBQLN, ubiquilin.",
    "ncbi_link": "ATG7: 10533
UBQLN1: 29979"
  },
  {
    "caption": "(C) Control cells (untransfected, right panel) or cells overexpressing Myc‐UBQLN2 and GFP‐LC3 (left panel) were transferred into starvation medium for 2 h. Localization of Myc‐UBQLN2 and GFP‐LC3 was analysed by immunoelectron microscopy using Myc (arrow) and GFP (arrowhead) antibodies coupled to 10 and 15 nm gold particles, respectively. Double‐membrane vacuoles (autophagosomes) in transfected cells (left panel) show increased staining by both antibodies compared with autophagosomes in untransfected cells (right panel). Scale bar, 0.5 μm. BAF A, bafilomycin A1; GFP, green fluorescent protein; UBQLN, ubiquilin.",
    "ncbi_link": "LC3: 440738///81631///84557
UBQLN2: 29978"
  },
  {
    "caption": "(C) Starvation‐induced cell death was assessed in cells expressing UBQLN1 or UBQLN1ΔUBA. The graph represents the mean of three experiments±s.e., with *P⩽0.05 (P=0.0017 by one‐way ANOVA test, comparing control, UBQLN1 and UBQLN1ΔUBA). No difference was found between control and UBQLN1ΔUBA at any time point. ANOVA, analysis of variance; GFP, green fluorescent protein; Pl, propidium iodide; UBA, ubiquitin‐associated; UBQLN, ubiquilin.",
    "ncbi_link": "UBQLN1: 29979"
  },
  {
    "caption": "(A) Autophagosome subcellular localization during starvation was analysed by microscopy in UBQLN‐ or autophagy‐related gene ATG5‐KD cells expressing GFP‐tagged microtubule associated protein 1 light chain 3 (GFP‐LC3).",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "B) Crystal structure of the Ago2-miRNA-target RNA ternary complex. Target RNA is colored blue. D) Close-up view of the Ago2-miRNA-target complex shows helix-7 docks into the minor groove of the guide:target duplex, directly contacting base pairs at positions g6 and g7.",
    "ncbi_link": "target RNA: 
Target RNA: "
  },
  {
    "caption": "Figure 2. Helix-7 is not required for target recognition. A) Plot of g2-g8 target RNA bound (0.1 nM) versus Ago2-miR122 concentration for wild type (WT), helix-7 double point mutant (MI-AA), and Ηhelix-7 Ago2. Average values from at least three independent experiments ± standard deviation (SD) are plotted. Top panel shows target RNA paired to seed region of the guide RNA (miRNA-122).",
    "ncbi_link": "target RNA: 
miR122: 406906"
  },
  {
    "caption": "B) Dissociation of a 32P-labeled target RNA (0.1 nM) from the Ago2-miR122 complex (1 nM) was monitored in the presence of unlabeled target RNA (100 nM). Fraction of the target RNA bound to Ago2-miR122 is plotted as a function of time for WT and Ηhelix-7 Ago2. Average values from at least three independent experiments ± SD were fit to single exponential decays.",
    "ncbi_link": "target RNA: 
miR122: 406906"
  },
  {
    "caption": "Figure 4. Helix-7 discourages non-Watson Crick pairing at g6 and g7. A-C) Plots of target RNA (0.1 nM) bound to Ago2 versus Ago2-miR122 (wild type and Ηhelix-7) concentration for targets with an increasing number of G:U wobble pairs in the seed 3' end. D) Plot of target RNA (0.1 nM) bound to Ago2 versus Ago2-miR122 concentration for a target with mismatches at positions g6-g8. For A-E, average values from at least three independent experiments ± SD are plotted.",
    "ncbi_link": "target RNA: 
miR122: 406906"
  },
  {
    "caption": "E) Bar plots of the Kd of wild type (left) Ηhelix-7 (right) Ago2-miR122 for indicated target RNAs. For A-E, average values from at least three independent experiments ± SD are plotted.",
    "ncbi_link": "target RNAs: 
miR122: 406906"
  },
  {
    "caption": "Figure 5. ΗHelix-7 Ago2 is sensitive to inhibition by off-target RNAs. A) Ago2-miRNA122 (1 nM) was incubated with a 32P-labeled, seed-matched target RNA (0.1 nM) in the presence of increasing concentrations of unlabeled a competitor RNA (top panel). Fraction target RNA bound to Ago2 is plotted as a function of off-target competitor RNA concentration. B) Fraction of target RNA bound to Ago2 in the presence of increasing concentrations of unlabeled total cellular RNA. For A-B, average values from at least three independent experiments ± SD are plotted.",
    "ncbi_link": "target RNA: 
target RNAs: 
miRNA122: 406906"
  },
  {
    "caption": "Figure 6. Helix-7 mutants display reduced target-binding rates. A) Ago2-miR122 complexes were mixed with a 32P-labeled seed matched target RNA; bound and free RNAs were then separated using a filter-binding apparatus at various times. Representative time course for target RNA (0.1 nM) binding to wild type, MI-AA, and Δhelix-7 Ago2 (1 nM). Average values from at least three independent experiments ± SD are plotted.",
    "ncbi_link": "target RNA: 
miR122: 406906"
  },
  {
    "caption": "B) Observed binding rates (kon, obs) plotted as a function of Ago2-miR122 concentration. Average values ± SD are plotted.",
    "ncbi_link": "miR122: 406906"
  },
  {
    "caption": "C) Arrival time distribution of single Ago2-miRNA complexes binding immobilized targets in a microfluidic chamber. The value is the average of three independent measurements.",
    "ncbi_link": "miRNA: "
  },
  {
    "caption": "Figure 7. Structure of a helix-7 Ago2 mutant. A) Superposition of wild type (white) and MI-AA (gray) Ago2. Helix-7 colored yellow; ordered region of the guide RNAs colored in red.",
    "ncbi_link": "guide RNAs: "
  },
  {
    "caption": "X-ray analysis of 6-months-old H2-c-fosLTR/Egfrwa/+ and H2-c-fosLTR/Egfrwa/wa littermates. Scale bars: 1cm",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "PET summation images (0-90 min) in horizontal (upper panel) and coronal view (lower panel) depicting [11C]Erlotinib distribution in one H2-c-fosLTR/Egfrwt mouse (M125). Anatomical structures are labelled with arrows (T, tumor; L, liver; H, heart; B, brain). Scale bars: 1cm Concentration-time curves of [11C]Erlotinib in bone tumors in right scapula of three H2-c-fosLTR/Egfrwt mice measured with PET. Broken line indicates threshold for in vitro effect of Erlotinib (1 µM)",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "X-ray analysis of 7-months-old H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob littermates. Scale bars: 1cm",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "µPET/CT analysis of 7-months-old H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob littermates Standardized uptake values (SUV) of the µPET-tracer Na[18F]F in the pelvic osteosarcoma of 4- and 7-months-old H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice. n=6 wt, 4 ∆Ob for 4 month time-point, n=6 wt, 3 ∆Ob for 7 month time-point",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "PCNA and cleaved Caspase 3 IHC staining and quantification shown as % positive cells (for PCNA) and as positive cells per mm² (for cleaved Caspase 3) in OS from H2-c-fosLTR/Egfrwt (n=6) and H2-c-fosLTR/Egfr∆Ob (n=5) mice. Scale bars: 100µm",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "Egfr, Ccnd1, c-fos and transgenic c-fos (c-fostg) mRNA expression levels in tumors of H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice normalized to Tbp. n=17 wt, 14 ∆Ob (Egfr, Ccnd1), n=16 wt, 13 ∆Ob (c-fos), n=16 wt, 14 ∆Ob (c-fostg",
    "ncbi_link": "Ccnd1: 12443
Egfr: 13649
c-fos: 14281
Tbp: 21374"
  },
  {
    "caption": "IHC staining and quantification showing pRSK2 (n=4), pCREB (n=7 wt, 6∆Ob) and c-Fos (n=5) positive cells (%) in OS from H2-c-fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob littermates. Scale bars: 100µm",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "Western Blot analysis of primary OS cells isolated from H2‑c‑fosLTR/Egfrwt and H2-c-fosLTR/Egfr∆Ob mice",
    "ncbi_link": "Egfr: 13649
c-fos: 14281
c‑fos: 14281"
  },
  {
    "caption": "c-fos and transgenic c-fos (c fostg) mRNA expression levels in primary H2-c-fosLTR OS cells after 4x in vitro passages, cultured under standard conditions (n=3 independent cell lines)",
    "ncbi_link": "c fos: 14281
c-fos: 14281"
  },
  {
    "caption": "Western Blot analysis of H2-c-fosLTR/Egfrwt OS cells treated for 24h with Erlotinib",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "c-fos and c-fostg mRNA expression levels in H2-c-fosLTR/Egfrwt OS cells treated for 24h with Erlotinib (10µM) or DMSO as control (n=4 independent cell lines)",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "Western Blot analysis of starved H2-c-fosLTR/Egfrwt OS cells, pre-treated with DMSO (1:1000), Afatinib (5µM), GSK2233470 (10µM), Rapamycin (10nM) or U0126 (10µM) for 30 minutes and stimulated with EGF (50ng/ml) as indicated",
    "ncbi_link": "Egfr: 13649
c-fos: 14281"
  },
  {
    "caption": "Western Blot analysis of primary OS cells isolated from a p53f/f Rb1f/f Osx-Cre mouse after 24h Erlotinib treatment",
    "ncbi_link": "Cre: 2777477
Rb1: 19645
Osx: 170574
p53: 22059"
  },
  {
    "caption": "c-fos mRNA expression levels in p53f/f Rb1f/f Osx-Cre OS cells treated for 24h with Erlotinib (10µM) (n=3)",
    "ncbi_link": "Cre: 2777477
c-fos: 14281
Rb1: 19645
Osx: 170574
p53: 22059"
  },
  {
    "caption": "Western Blot analysis of starved p53f/f Rb1f/f Osx-Cre OS cells, pre-treated with DMSO (1:1000) or Afatinib (5µM) for 30 minutes and stimulated with EGF (50ng/ml) as indicated",
    "ncbi_link": "Cre: 2777477
Rb1: 19645
Osx: 170574
p53: 22059"
  },
  {
    "caption": "X-ray analysis of 6-months-old H2-c-fosLTR and H2-c-fosLTR/ColAREG littermates. Scale bars: 1cm",
    "ncbi_link": "AREG: 11839
Col: 12842
c-fos: 14281"
  },
  {
    "caption": "Bone tumor number per mouse at 5-6 months of age (n=22 wt, 13 ColAREG)",
    "ncbi_link": "AREG: 11839
Col: 12842"
  },
  {
    "caption": "Quantification of tumor size in tibiae at 5-6 months of age (n=22 wt, 13 ColAREG)",
    "ncbi_link": "AREG: 11839
Col: 12842"
  },
  {
    "caption": "Alkaline Phosphatase (ALP) levels in the serum at endpoint (age = 5-6 months; n=29 wt, 19 ColAREG)",
    "ncbi_link": "AREG: 11839
Col: 12842"
  },
  {
    "caption": "c-fos mRNA expression levels in osteosarcomas of H2-c-fosLTR (n=11) and H2-c-fosLTR/ColAREG mice (n=14)",
    "ncbi_link": "AREG: 11839
Col: 12842
c-fos: 14281"
  },
  {
    "caption": "Western Blot analysis of bone tumor protein lysates from H2-c-fosLTR and H2-c-fosLTR/ColAREG mice",
    "ncbi_link": "AREG: 11839
Col: 12842
c-fos: 14281"
  },
  {
    "caption": "(A, B) Actively dividing cells labelled by BrdU and Ki67 are reduced in the SGZ of DSCR1 mutants compared to that of wild type mice. Brain sections were prepared 1 day after BrdU injection. The white box area is magnified in the lower panels: DAPI (blue), Ki67 (green), and BrdU (red). Arrow heads indicate BrdU and Ki-67 double positive cells in the SGZ.",
    "ncbi_link": "DSCR1: 54720"
  },
  {
    "caption": "(A) miR-124 expression is altered in DSCR1 mutants. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 animals for each condition, *P< 0.01.",
    "ncbi_link": "DSCR1: 54720"
  },
  {
    "caption": "(B) Promoter activity of miR-124 in Neuro2 A cells with DSCR1 reduction or overexpression. Firefly luciferase reporter under the control of miR-124 promoter is measured. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 for each condition, *P< 0.05, **P< 0.01.",
    "ncbi_link": "luciferase: 
miR-124: 70441///268755
DSCR1: 54720"
  },
  {
    "caption": "(C) Bisulfite sequencing analyses of the miR-124 promoter. Each CpG site is indicated, and the methylation status of two different regions are shown. Open and filled circles represent unmethylated and methylated CpG sites, respectively. The percentage of methylated CpGs among total number of CpGs is also shown.",
    "ncbi_link": "miR-124: 70441///268755"
  },
  {
    "caption": "(D) Neuro2A cells containing DSCR1shRNA show increased activity of miR-124 promoter measured. The miR-124 promoter was inserted in front of the luciferase reporter. Site-directed mutation of two methylation sites (31 and 58) in the promoter shows the luciferase activity similar to that of DSCR1 reduction. Values are shown as mean ± SEM, and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 for each condition, *P< 0.05.",
    "ncbi_link": "luciferase: 
miR-124: 70441///268755
DSCR1: 54720"
  },
  {
    "caption": "(E) Overexpression of DSCR1 reduced the luciferase activity, while removing all methylation sites in the miR-124 promoter increases it. Values are shown as mean ± SEM, and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 for each condition, *P< 0.05.",
    "ncbi_link": "miR-124: 70441///268755
DSCR1: 54720"
  },
  {
    "caption": "(A) DSCR1 binds to TET1 introns. The binding affinity of DSCR1 to the intron 8 of TET1 decreased with increased dosage of U1 snRNA and U2 snRNA.",
    "ncbi_link": "TET1: 52463"
  },
  {
    "caption": "(B) DSCR1 missing RNA recognition motif (△RRM) does not bind to the TET1 intron 8.",
    "ncbi_link": "DSCR1: 54720
TET1: 52463"
  },
  {
    "caption": "(C, D) Schematic diagram of the luciferase reporter separated by TET1 intron 8 and 9 or GAPDH intron 3 and 4. DSCR1 reduction increases the activity of this luciferase construct, while DSCR1 overexpression decreases its activity. In contrast, altering DSCR1 levels did not affect luciferase activity of the construct containing GAPDH introns. Values are shown as mean ± SEM, and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 for each condition, *P< 0.05, **P< 0.01. ***P< 0.001.",
    "ncbi_link": "luciferase: 
GAPDH: 14433
DSCR1: 54720
TET1: 52463"
  },
  {
    "caption": "(E) TET1 protein expression in the dentate gyrus region of hippocampus of DSCR1 mutants. TET1 is increased in DSCR1 knockout, while it is decreased in DSCR1 transgenic mice. Values are shown as mean ± SEM, and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 3 animal for each condition, *P< 0.05, **P< 0.01.",
    "ncbi_link": "DSCR1: 54720"
  },
  {
    "caption": "(A) Genotype of Ts65Dn/DSCR1+/- mouse was confirmed by detecting markers for Ts65Dn and DSCR1 KO",
    "ncbi_link": "DSCR1: 54720
Ts65Dn: 21101"
  },
  {
    "caption": "(B) Expression of the DSCR1 mRNA in Ts65Dn mouse was increased about 2.5 folds compared to that of wild type. However, Ts65Dn/DSCR1+/- mouse showed normal level of DSCR1 mRNA transcript. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N=3 for each condition, *P< 0.05.",
    "ncbi_link": "DSCR1: 54720
Ts65Dn: 21101"
  },
  {
    "caption": "As expected, the levels of TET1 are decreased in Ts65Dn mouse, however Ts65Dn/DSCR1+/- mouse restores the TET1 mRNA expression. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. ß-actin was used for normalization. N = 3 (Diploid), 3 (Ts65Dn), 4 (Ts65Dn/DSCR1+/-) mice, *P< 0.05, **P< 0.01.",
    "ncbi_link": "ß-actin: 11461
DSCR1: 54720
Ts65Dn: 21101
TET1: 52463"
  },
  {
    "caption": "As expected, the levels of miR-124 are decreased in Ts65Dn mouse, however Ts65Dn/DSCR1+/- mouse restores the miR-124 expression. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. ß-actin was used for normalization. N = 3 (Diploid), 3 (Ts65Dn), 4 (Ts65Dn/DSCR1+/-) mice, *P< 0.05, **P< 0.01.",
    "ncbi_link": "ß-actin: 11461
miR-124: 70441///268755
DSCR1: 54720
Ts65Dn: 21101"
  },
  {
    "caption": "(E, F) The number proliferating progenitor neurons identified by BrdU and Ki-67 double staining is restored in the SGZ of Ts65Dn/DSCR1+/- mouse compared to that of Ts65Dn mouse. The white box area is magnified in the lower panels: DAPI (blue), Ki67 (green), and BrdU (red). Arrow heads indicate BrdU and Ki-67 double positive cells in the SGZ. Scale bars: 100 μm in the large image and 10 μm in magnified image. Each hippocampal section was 40 μm in thickness, and total 6 hippocampi were used for analysis. Values are shown as mean ± SEM and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 6 (control), 5 (Ts65Dn), 3 (Ts65Dn/DSCR1+/-) animals, *P< 0.05.",
    "ncbi_link": "DSCR1: 54720
Ts65Dn: 21101"
  },
  {
    "caption": "(G-J) Ts65Dn has learning and memory defects, but Ts65Dn/DSCR1+/- mouse clearly rescues learning and memory defects to control levels. Values are shown as mean ± SEM, and tested for statistical significance by one-way ANOVA followed by Bonferroni post hoc test. N = 8 (control), 5 (Ts65Dn), 10 (Ts65Dn/DSCR1+/-) animals, *P< 0.001 (G, H). *P< 0.05 (I), **P< 0.01 (I). (J) Open-field analysis shows no defects in movement of tested animals. Values are shown as mean ± SEM, N = 6 (control), 5 (Ts65Dn), 3 (Ts65Dn/DSCR1+/-) animals.",
    "ncbi_link": "DSCR1: 54720
Ts65Dn: 21101"
  },
  {
    "caption": "Binding of recombinant (r)CEACAM1 (CC1)-HIS (10 μg/mL) to (A) a panel of Gram-positive bacteria, namely Enterococcus faecalis, Enterococcus faecium, Group A Streptococcus (GAS), Group B Streptococcus (GBS), Group C Streptococcus (GCS), Group G Streptococcus (GGS), Streptococcus pneumoniae, Staphylococcus aureus, (B) an expanded collection of GBS isolates, with serotype and carriage of bac gene shown. rCC1 binding to live bacteria was quantified by a secondary anti-His-FITC monoclonal antibody (mAb). Mean and standard deviation (SD) values are reported for n = 3 independent experiments. In (B), GBS strains from left to right are A909, BS39, 515, BS22, H36B, BS29, 18RS21, BM110, COH1, SBL3066, NCTC10/84, SB35, SB10, SB20, BS26.",
    "ncbi_link": "bac: "
  },
  {
    "caption": "Adhesion of WT, ∆bac and ∆bac + pLZ.bac complemented A909 strains to human CC1- or CC5-expressing CHO transfectants, or empty vector control cells. Mean and SD from n = 5 independent replicates is displayed.",
    "ncbi_link": "bac: 
CC1: 634
CC5: 1048"
  },
  {
    "caption": "Binding of rCC1-N to dynabeads (DB) coated with β-IgI3 wild type (WT) or mutants. Mutation of β-IgI3 residues 42, 46 and 53 lead to significant changes in CC1-N binding capacity.",
    "ncbi_link": "β-IgI3: "
  },
  {
    "caption": "D The mRNA expression level of METTL3 in sorafenib-sensitive (n=3) and sorafenib-resistant (n=3) human liver tumors. Data information: In all relevant panels, ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "E Expression of METTL3 was significantly down-regulated in advanced stage of liver cancer from TCGA.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "F METTL3 RNA levels between naïve HepG-2 cells (n=3) and sorafenib-resistant HepG-2 cells (n=10). Data information: In all relevant panels, ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "A-B Clonogenic survival of METTL3-knockdown (A) and METTL3-overexpression (B) in normal liver cell line WRL68 cells for 7 days in normoxia condition (21% O2) and quantification of clusters in A-1 and B-1, respectively. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "C-D The IC50 of METTL3-knockdown SMMC-7721 cells (C) and Bel-7402 cells (D) after treated with sorafenib for 24h under hypoxia condition (1%O2). Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "E Overexpression of wild type METTL3 or catalytic mutant METTL3 in sorafenib-resistant HepG-2 cells.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "F The global RNA m6A level in sorafenib-resistant HepG-2 cells with wild type METTL3-overexpression or catalytic mutant METTL3-overexpression by dot-blotting assay.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "G-I Rescue of shRNA-resistant wild type METTL3 but not catalytic mutant METTL3 sensitized METTL3-knockdown SMMC-7721 cells (G), Bel-7402 cells (H) and sorafenib-resistant HepG-2 cells (I) to sorafenib treatment. The IC50 of the cells was measured after treated with sorafenib for 24h under hypoxia condition (1%O2). Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "J Cell survival assay of sorafenib-resistant HepG-2 cells with wild type METTL3 overexpression or catalytic mutant METTL3 overexpression after treated with sorafenib for 24h under hypoxia condition (1%O2). Scale bar, 1mm.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "K Capillary-like structures in HUVECs treated with the tumor-conditioned medium (TCM) from control HCCs and METTL3-knockdown HCCs cultured under hypoxic conditions for 48 h. Quantification of the number of tubes with image J in K-1. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "L-M The relative mRNA expression levels of angiogenesis genes were detected in SMMC-7721 cells (L) and Bel-7402 cells (M) with METTL3-knockdown by RT-PCR assay. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "N The protein levels of VEGF-A in METTL3-knockdown HCCs. O The protein levels of PDGF-B in METTL3-knockdown HCCs. ",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "A Electron micrographs of METTL3-knockdown SMMC-7721 cells under hypoxia for 48 h.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "Protein levels of LC3 I/II in METTL3-knockdown SMMC-7721 (B), Bel-7402 (C) cells under hypoxia condition for 48h.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "F-H Overexpression of shRNA-resistant wild type METTL3 but not catalytic mutant METTL3 rescue autophagy phenotype in METTL3-knockdown SMMC-7721 cells (F), Bel-7402 cells (G) and sorafenib-resistant HepG2 cells (H) by representative immunostaining images of LC3 under hypoxia condition for 48h. Scale bar, 200μm. Quantification of the numbers of GFP-LC3 puncta/cell by Imaris in F-1, G-1 and H-1, respectively. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "I-K Protein levels of LC3 I/II in METTL3-knockdown SMMC-7721 cells (I), Bel-7402 cells (J) and HepG-2 cells (K) treated with or without 3-MA under hypoxia condition for 24h.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "A Gene Set Enrichment Analysis (GSEA) output images of cellular response to stress pathways displaying a correlation of differentially regulated genes in METTL3-knockdown HepG2, SMMC-7721 and Bel-7402 cells with the C5. biological process symbol set. (p < 0.001).",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "C Protein level of FOXO3 in METTL3-knockdown HCCs under hypoxia for 48h.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "D Half-life of FOXO3 mRNA in Bel-7402 cells and correspondent METTL3-knockdown Bel-7402 cells treated with actinomycin D.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "E Half-life of FOXO3 protein in Bel-7402 cells and correspondent METTL3-knockdown Bel-7402 cells treated with cycloheximide. Quantification of the protein optical density by Image J in E-1.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "F Analysis of FOXO3 mRNA in non-ribosome portion (<40S), 40S, 60S, 80S and polysome for the METTL3-knockdown Bel-7402 cells compare to control cells under hypoxia for 48h. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "G Knockdown of YTHDF1 and YTHDF2 in Bel-7402 cells by lentiviral shRNAs.",
    "ncbi_link": "YTHDF1: 54915
YTHDF2: 51441"
  },
  {
    "caption": "H Knockdown of YTHDF1 but not YTHDF2 abolished the increase of FOXO3 protein level in METTL3-overexpressing Bel-7402 cells. Quantification of the protein optical density by Image J in H-1 and H-2. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "METTL3: 56339
YTHDF1: 54915
YTHDF2: 51441"
  },
  {
    "caption": "I RNA level of FOXO3 in YTHDF1-knockdown Bel-7402 cells by RT-PCR. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
YTHDF1: 54915"
  },
  {
    "caption": "J The m6A-IP sequencing under hypoxia proved the m6A modification participated in regulation of FOXO3. The YTHDF1 binding site locates at the 3'UTR of FOXO3.",
    "ncbi_link": "FOXO3: 2309
YTHDF1: 54915"
  },
  {
    "caption": "L Relative luciferase activity of the wild-type and mutant form of FOXO3 3'UTR reporter vectors in Bel-7402 cells with various levels of METTL3 and YTHDF1. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339
YTHDF1: 54915"
  },
  {
    "caption": "M Knockdown of METTL3 reduced the m6A methylation in FOXO3 mRNA by the m6A MeRIP analysis. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "N Knockdown of METTL3 reduced the m6A methylation in FOXO3 mRNA by the YTHDF1-RIP analysis. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339
YTHDF1: 54915"
  },
  {
    "caption": "O Correlation analysis of the RNA expression levels of METTL3 and FOXO3 in liver tumor cohort (Kim-90) by Pearson.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "P Correlation analysis of the RNA expression levels of YTHDF1 and FOXO3 in liver tumor cohort (Kim-90) by Pearson.",
    "ncbi_link": "FOXO3: 2309
YTHDF1: 54915"
  },
  {
    "caption": "A Validation of biomarker genes related to autophagy in FOXO3-knockdown Bel-7402 cells by RT-PCR. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309"
  },
  {
    "caption": "C Protein levels of LC3 I/II in FOXO3-knockdown SMMC-7721 cells.",
    "ncbi_link": "FOXO3: 2309"
  },
  {
    "caption": "D Overexpression of FOXO3 in sorafenib-resistant HepG-2 cells by Western blot.",
    "ncbi_link": "FOXO3: 2309"
  },
  {
    "caption": "E Protein levels of LC3 I/II in METTL3-knockdown & FOXO3-overexpression SMMC-7721 cells under hypoxia for 48 h.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "F Electron micrographs of METTL3-knockdown SMMC7721 cells and METTL3-knockdown & FOXO3-overexpression SMMC7721 cells under hypoxia for 48 h. G Representative Immunostaining images of LC3 in METTL3-knockdown SMMC7721 cells and METTL3-knockdown & FOXO3-overexpression SMMC7721 cells under hypoxia for 48 h. Scale bar, 200μm. The quantification of the numbers of GFP-LC3 puncta/cell by Imaris in G-1. H Representative Immunostaining images of LC3 in naïve HepG-2 cells and sorafenib-resistant HepG-2 cells under hypoxia for 48 h. Scale bar, 200μm. The quantification of the numbers of GFP-LC3 puncta/cell by Imaris in H-1. I The IC50 of METTL3-knockdown SMMC7721 cells with overexpressing FOXO3 after treated with sorafenib for 24h under hypoxia condition. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "J The IC50 of naïve HepG-2 cells and sorafenib-resistant HepG-2 cells with overexpressing FOXO3 after treated with sorafenib for 24h under hypoxia condition. Data information: In all relevant panels, *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001; Two-tailed t-test. Data are presented as mean ± SD and are representative of 3 independent experiments.",
    "ncbi_link": "FOXO3: 2309"
  },
  {
    "caption": "K Cell survival assay of METTL3-knockdown SMMC7721 cells with overexpressing FOXO3 after treated with sorafenib for 24h under hypoxia condition.",
    "ncbi_link": "FOXO3: 2309
METTL3: 56339"
  },
  {
    "caption": "L Cell survival assay of naïve HepG-2 cells and sorafenib-resistant HepG-2 cells with overexpressing FOXO3 after treated with sorafenib for 24h under hypoxia condition.",
    "ncbi_link": "FOXO3: 2309"
  },
  {
    "caption": "A Depletion of METTL3 in Hepa1-6 cells by CRISPR-Cas9 knockout enhanced sorafenib-resistance in vivo.",
    "ncbi_link": "Cas9: 
CRISPR: 
METTL3: 56335"
  },
  {
    "caption": "D Knockdown of METTL3 slightly increased liver tumor growth treated with sorafenib in orthotopic xenograft mouse model. Stable METTL3-knockdown Bel-7402 cells and control cells were injected into the liver of each NOD/SCID mouse. 3 weeks after injection, livers were separated for pathological analysis. Red circle indicates tumors in the livers.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "F Overexpression of FOXO3 rescued sorafenib-resistance mediated by METTL3-knockdown in xenograft liver tumors. Representative xenograft tumors at endpoint, containing 6 groups.",
    "ncbi_link": "FOXO3: 56484
METTL3: 56335"
  },
  {
    "caption": "I Knockdown of METTL3 by siRNA in PDX#1 and PDX#2 tissues were confirmed by Western blot.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "(A-B) Immunofluorescence (IF) analysis of IκBα in sections from murine small intestine of 2 month-old WT (A) and Lgr5-GFP reporter mice (B). Scale bars, 50μm.",
    "ncbi_link": "GFP: 
Lgr5: 14160"
  },
  {
    "caption": "IF analysis of P-IκBα in the intestine of 2 month-old Lgr5-GFP reporter mice (D), and quantification of P-IκBα positivity inside the Lgr5-GFP population. A minimum of 30 crypts was counted in 3 Lgr5-GFP mice. Scale bars in D, 50 μm.",
    "ncbi_link": "GFP: 
Lgr5: 14160"
  },
  {
    "caption": "(A) Representative images of P4 and P6 mice of the indicated IκBα genotypes.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "D-G (D) Immunohistochemical (IHC), IF ­and Alcian Blue staining with quantification of P6 IκBα WT and KO intestines (D), 2 month-old IκBβ;IκBε KO (E) and 2 month-old IκBαNES mice (F and G). A minimum of 50 crypts/villus was counted per genotype (3 mice). Data information: bars represent mean values ± standard error of the mean (s.e.m); p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, ***p-value<0.0005, * p-value<0.05, n.s. no significant. Scale bars in D, E, F and G, 50 μm.",
    "ncbi_link": "IκBα: 18035
IκBβ: 18036
IκBε: 18037"
  },
  {
    "caption": "(B) IF analysis of EphB2 in P6 WT and IκBα KO intestine. Data information: Scale bars , 25 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(F) Table indicating the top 15 up-regulated genes in the IκBα KO EphB2-high signature including 11 genes in the fetal ISC signature (in orange).",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(I) qPCR analysis of the indicated genes in purified Lgr5+ cells from the different IκBα backgrounds. 4 WT and 1 KO mice were analyzed with at least three technical replicates. Bars represent mean values ± standard error of the mean (s.e.m). p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, **p-value<0.005, *p-value<0.05, n.s. no significant.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(A) IF analysis of c-Rel and RelA/p65 in P6 WT and IκBα KO intestines. Scale bars in 25 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(B) Number of peaks from p65 ChIP-sequencing analysis associated with the different genomic localizations was obtained merging two biological replicates per condition (n=2 P6 WT and n=2 P6 IκBα KO intestinal crypt cells). Data from individual experiments have been deposited at GSE131187.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "IF analysis of active Notch1 (ICN1) (C) in the indicated IκBα backgrounds at P6 intestines. Scale bars in 25 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "IF analysis of β-catenin (D) in the indicated IκBα backgrounds at P6 intestines. Scale bars 25 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(F) Table indicating the methylation-related genes (PRC2 members and KDM6 demethylase) differentially express between IκBα WT and KO EphB2-high sorted cells (RNA-seq).",
    "ncbi_link": "PRC2: 103551
KDM6: 216850///22289
IκBα: 18035"
  },
  {
    "caption": "(J) Representation of IκBα (n=4) and H3K27me3 (n=2) distribution (from ChIP-sequencing) and expression levels (from RNA-sequencing) in the genomic region of Litaf.",
    "ncbi_link": "Litaf: 56722"
  },
  {
    "caption": "(A) Representative stereoscopic image of P6 WT and IκBα KO-derived intestinal organoids. Scale bars in A, 100 μm",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(B) IHC analysis with the indicated antibodies and Alcian Blue staining of WT and IκBα KO-derived organoids. Scale bars in B 50 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(C) qPCR analysis of the indicated ISC genes in WT and IκBα KO-derived organoids. Data information: 3 technical replicates of a minimum of two organoids per genotype were analyzed Bars represent mean values ± standard error of the mean (s.e.m). p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, **p-value<0.005, * p-value<0.05.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(E) qPCR analysis of the indicated fetal genes in WT and IκBα KO-derived organoids. Data information: 3 technical replicates of a minimum of two organoids per genotype were analyzed Bars represent mean values ± standard error of the mean (s.e.m). p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, **p-value<0.005, * p-value<0.05.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(F) Western blot analysis of control and IκBα-deleted organoids using CRISPR-Cas9 technology.",
    "ncbi_link": "CRISPR: 
Cas9: 901176
IκBα: 18035"
  },
  {
    "caption": "(G) Representative stereoscopic image of WT and IκBα-deleted organoids. Scale bars in G, 50 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "A) Representative stereoscopic images and Western blot analysis of IκBα KO organoids infected with the indicated sh-RNA for NF-κB elements. Data information Scale bars in A, 100 μm,",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(B) qPCR analysis of the indicated ISC and differentiation genes in the different sh-RNA treated organoids. The canonical NF-κB target gene Cxcl10 is shown as positive control of the experiment. Data information 3 technical replicates of a minimum of two organoids per condition were analyzed. Bars represent mean values ± standard error of the mean (s.e.m); p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, ***p-value<0.0005, **p-value<0.005, * p-value<0.05, n.s. no significant.",
    "ncbi_link": "Cxcl10: 15945"
  },
  {
    "caption": "(C) Representative stereoscopic images of IκBα KO organoids untreated or treated with the PRC2 inhibitor EPZ-6438. Data information Scale bars in 50 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(D-E) qPCR analysis of the indicated adult and fetal ISC genes (D) and elements of the Notch and IFN pathway (E) (differentially expressed in IκBα KO organoids) in IκBα KO organoids untreated or treated with the PRC2 inhibitor EPZ-6438. Data information: 3 technical replicates of a minimum of two organoids per condition were analyzed. Bars represent mean values ± standard error of the mean (s.e.m); p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, ***p-value<0.0005, **p-value<0.005, * p-value<0.05, n.s. no significant.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(F) Representative stereoscopic images of IκBα KO organoids treated with dexamethasone as IFN inhibitor and DAPT as Notch inhibitor. Data information Scale bars in F, 50 μm.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(G) qPCR analysis of IκBα KO organoids untreated or treated with dexamethasone and DAPT. Data information: 3 technical replicates of a minimum of two organoids per condition were analyzed. Bars represent mean values ± standard error of the mean (s.e.m); p values were derived from an unpaired t-test, two-tailed, ****p-value<0.0001, ***p-value<0.0005, **p-value<0.005, * p-value<0.05, n.s. no significant.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(D) qPCR analysis of the indicated genes in WT and IκBα KO organoids treated with TNFα and collected at the indicated time-points. 3 technical replicates of organoids from each genotype were analyzed.",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "(E-F) Representative images of the colonic tissue from 2 months-old DSS-treated WT and IκBα KO mice are shown. Alcian Blue staining was used to identify the mucus-secreting goblet cells in the colonic glands and Ki67 as proliferation marker. Nuclear counterstain is Fast Red. The table shows number of ulcerations present in the intestines of mice analysed (3 WT, 2 IκBα KO). Data information: Scale bars in E and F, 100 μm",
    "ncbi_link": "IκBα: 18035"
  },
  {
    "caption": "C Genomic PCR analysis indicating the existence of MpFGMYB in both male [Y] and female [X] genomes of M. polymorpha. Two biological replicates were analyzed. Constitutively expressed MpEF1α was used as a control.",
    "ncbi_link": "MpEF1α: 
MpFGMYB: "
  },
  {
    "caption": "D Real-time RT-PCR analyses indicating preferential accumulation of MpFGMYB transcripts in female sexual organs and the sporophytes. MpEF1α was used for normalization. Measurements of six biological replicates for thalli and sporophyte, and three biological replicates for gametangiophore are plotted. Bars represent mean ± SD. Symbols above the bars indicate grouping by p <0.05 in a Tukey-Kramer test.",
    "ncbi_link": "MpEF1α: 
MpFGMYB: "
  },
  {
    "caption": "F MpFGMYB-Citrine fusion proteins expressed using the 5′- and 3′-flanking sequences rescued the Mpfgmybge-1 mutant and accumulated in the nuclei of the egg and the ventral canal cell (VCC) Scale bar, 10 µm. Magenta, chlorophyll autofluorescence; green, Citrine fluorescence.",
    "ncbi_link": "Mpfgmyb: "
  },
  {
    "caption": "B Diagnosis of genetic sex using Y- and X-chromosome-linked rbm27 and rhf73 markers, respectively. Two biological replicates were analyzed for each genotype.",
    "ncbi_link": "rbm27: 
rhf73: "
  },
  {
    "caption": "A-C DAPI-staining visualization of sperm formation in wild-type male (A), Mpfgmyb [X] (B), and Mpfgmyb [Y] (C) plants. Note that background DAPI staining visualizes flagella (arrows) in addition to nuclei (arrowheads). (B′) is an enlarged image of the boxed region in (B), visualizing an incompletely condensed nucleus. Scale bars, 5 µm.",
    "ncbi_link": "Mpfgmyb: "
  },
  {
    "caption": "D RT-PCR analysis indicating acquisition of male-like autosomal gene expression patterns in Mpfgmyb [X] antheridiophores. Two independent Mpfgmyb [X] mutant alleles were analyzed.",
    "ncbi_link": "Mpfgmyb: "
  },
  {
    "caption": "E, F TEM analyses visualizing the abnormal arrangement of axonemal microtubules in Mpfgmyb [X] sperm (F), as compared with those of wild-type males (E). Scale bars, 100 nm.",
    "ncbi_link": "Mpfgmyb: "
  },
  {
    "caption": "A RNA-seq analysis showing male-specific accumulation of lncRNAs derived from the MpFGMYB 3′ region. Diagrams illustrate wild-type and mutant MpFGMYB/SUF loci. Folded lines with a ∆ symbol indicate a deletion.",
    "ncbi_link": "MpFGMYB: 
SUF: "
  },
  {
    "caption": "B RT-PCR analysis of wild-type and genetically male suf mutants revealed loss of SUF expression and gain of MpFGMYB expression after induction of reproductive growth by far-red irradiation. Two independent suf mutant alleles were analyzed. The SUF primer pair used here flanked an intron and the duplicated bands of SUF likely represent spliced and unspliced forms.",
    "ncbi_link": "suf: 
SUF: 
MpFGMYB: "
  },
  {
    "caption": "A gametangiophore of MpEF1pro:SUF/suf-30ge [Y], indicating the inability of transgenic SUF overexpression in rescuing the feminization phenotype of sufge [Y]. Scale bar, 2mm.",
    "ncbi_link": "MpEF1: 
SUF: 
suf: 
suf-30: "
  },
  {
    "caption": "B Real-time RT-PCR analyses confirming SUF transcript accumulation in SUF-overexpressing lines. Constitutively expressed MpEF1α was used as control. Measurements of six biological replicates for WT [Y], and three biological replicates for each SUF-overexpressing line are plotted. Data information: bars represent mean ± SD. Asterisks indicate significant differences from WT [Y] (B) (p <0.05, two-tailed Student's t-test).",
    "ncbi_link": "SUF: 
MpEF1α: "
  },
  {
    "caption": "D Real-time RT-PCR measurement of MpFGMYB transcript levels. Three biological replicates are analyzed for each line. Data information bars represent mean ± SD. Asterisks indicate significant differences from WT [X] (D) (p <0.05, two-tailed Student's t-test).",
    "ncbi_link": "MpFGMYB: "
  },
  {
    "caption": "E-H Gametangiophores (E, G) and gametangia (F, H) of gMpFGMYB-S [Y] (E, F) and gMpFGMYB-L [Y] (G, H). Scale bars, 1 mm (E, G), 50 μm (F), 100 μm (H).",
    "ncbi_link": "gMpFGMYB-L: 
gMpFGMYB-S: "
  },
  {
    "caption": "(a) Hippocampal tissues obtained from Nrf2 (−/−) (6 months old, one male and two female) or wild-type (WT) (11 months old, two male and one female) mice were immunoblotted with a Nrf2 antibody, 12E8, PHF1, a monoclonal to total tau (Tau5) or a polyclonal to total tau (Tau) antibody. The asterisk to the left of the Nrf2 blot designates the position at which a nonspecific band migrated. The relative molecular masses (kDa) are indicated to the left of each blot. (b) Bar graphs represent the relative optical density of phosphorylated or total tau in the hippocampal tissues. n=6 (These data are based on the mouse hippocampi immunoblotted in Supplementary Fig. 1). Data shown are mean±s.e. and were analysed using Student's t-test. (**P0.01; ***P0.001)",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "Brain cortical tissue obtained from Nrf2 (−/−) (6 months old, one male and two female) or wild-type (11 months old, two male and one female) mice were separated into sarkosyl-soluble (SS) and insoluble (SI) fractions as described in the Methods. The level of total tau was analysed by immunoblotting using a monoclonal antibody to total tau (Tau5). The relative molecular masses (kDa) are indicated to the left of each blot. Bar graph represents the relative optical density of sarkosyl-insoluble tau normalized with that of sarkosyl-soluble tau. n=3. Data shown are mean±s.e. and were analysed using Student's t-test. (*P0.05).",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "Mouse brains were obtained from wild-type (11 months old, one male; 5 months old, one female; 12 months old, two female) and Nrf2 (−/−) (10 months old, two male and two female) mice. (a)Mouse brain tissues were homogenized in the lysis buffer, and 10 μg of lysates was incubated with 2 μg of GST-tau protein at 37°C for 30 min in the presence or absence of 1 mM ATP. The levels of tau phosphorylated at Ser262/Ser356 and Ser396/Ser404 were analysed by immunoblotting using a 12E8 and PHF1 antibodies, respectively. GST-tau was detected with a monoclonal GST antibody (GST-tau; Supplementary Fig. 4). Bar graph of the relative optical density of phosphorylated tau normalized to actin. Data shown are mean±s.e. of duplicated independent experiments and were analysed using Student's t-test.",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "Mouse brains were obtained from wild-type (11 months old, one male; 5 months old, one female; 12 months old, two female) and Nrf2 (−/−) (10 months old, two male and two female) mice. (b) Mouse brain tissues were homogenized in the phosphatase storage buffer, and phosphatase activity in the lysates was quantified using the serine/threonine phosphatase assay system (Promega) by measuring the dephosphorylation of a phosphopeptide, RRA(pT)VA in the presence or absence of okadaic acid (OA, 20 nM). PP2A activity was defined as the activity inhibited by the addition of OA to the phosphatase reaction mixture. n=4. Data shown are mean±s.e. of three independent experiments and were analysed using Student's t-test.",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "(c) HEK293-TN cells were co-transfected with the plasmid expressing tau together either with siRNA of beclin-1 or scramble RNA as a control, which was kept for 48 h.",
    "ncbi_link": "beclin-1: 8678"
  },
  {
    "caption": "(b) In hippocampal tissues from Nrf2 (−/−) (5 months old, one male; 11 months old, one female; 5 months old, one female; 12 months old, three female) or wild-type (10 months old, four male and two female) mice, the relative mRNA level of each gene compared with that of wild-type mice. n=6.",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "(c) The levels of p62/SQSTM1, Keap1, mouse NDP52 (mNDP52) and Hsp70 in Nrf2 (−/−) or wild-type mice were examined by immunoblotting. The asterisk on the Nrf2 panel indicates a nonspecific band.",
    "ncbi_link": "Nrf2: 18024
Nrf2: Q60795///18024"
  },
  {
    "caption": "(d,e: upper panel) Primary cortical neurons (DIV 5) (d) and SH-SY5Y cells (e) were treated with SFN for 24 h, and the expression levels of rat and human NDP52 (rNDP52 and hNDP52) examined by immunoblotting using anti-NDP52 antibody. The relative molecular masses (kDa) are indicated to the left of each blot. (d,e: low panel) Primary cortical neurons (DIV 5) (d) and SH-SY5Y cells (e) transiently transfected with the pGL4.14/human NDP52 promoter (2,173 bp) luciferase reporter plasmid were treated with SFN for 24 h, and assayed for the luciferase activity.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(b) CN1.4 cortical cells and SH-SY5Y cells were transiently transfected with the reporter plasmids with the human NDP52 promoter (2,317 bp or deleted mutants), and luciferase activity was assayed 24 h after transfection.",
    "ncbi_link": "luciferase: 
NDP52: 10241"
  },
  {
    "caption": "(c) SH-SY5Y cells were co-transfected with the reporter plasmids with human NDP52 promoter (wild or deleted mutants) along with either the mock plasmid (pcDNA3.1) or the plasmid expressing Nrf2, and the luciferase activity was assayed 24 h after transfection. (d) SH-SY5Y cells were transiently co-transfected with the reporter plasmids with human NDP52 promoter or its mutant plasmid in which the putative ARE sequence was site-directly mutated (X), together with the mock plasmid (pcDNA3.1) or the plasmid expressing human Nrf2. The luciferase activity was assayed after 24 h. The induced luciferase activity with co-expression with Nrf2 was not observed in a mutant NDP52 promoter in which all three ARE sites (−2,057, −1,023 and −94) were site-directly mutated, indicating these three sites of five ARE cis-acting elements are functional. Data shown are mean±s.d. of three independent experiments and were analysed using Student's t-test. (*P0.05; **P0.01; ***P0.001).",
    "ncbi_link": "luciferase: 
NDP52: 10241
Nrf2: 4780"
  },
  {
    "caption": "(a) Primary cortical neurons were transduced with lentivirus expressing sh-RNA for Nrf2 or rat NDP52 (rNDP52), or a scrambled sh-RNA at DIV 1, and were maintained until DIV 6. The levels of tau phosphorylated at Ser262/Ser356 and Ser396/Ser404 were analysed by immunoblotting using 12E8- and PHF1-specific antibodies, respectively. Total tau was detected with a polyclonal tau-specific antibody (Tau). The relative molecular masses (kDa) are indicated to the left of each blot. (b) Bar graph of the relative optical density of phosphorylated tau normalized to actin. Data shown are mean±s.e. of three independent experiments and were analysed using Student's t-test. (*P0.05; ***P0.001)",
    "ncbi_link": "NDP52: 303479
Nrf2: 83619"
  },
  {
    "caption": "(c,d) Primary cortical neurons were transduced with a control lentivirus (FIGB) or with one expressing humanNDP52 (hNDP52) at DIV 1. To induce autophagy, trehalose (150 mM) was added at DIV 5 and the neurons incubated for 24 h (DIV 6). Primary cortical neurons were fixed with 4% paraformaldehyde, and stained with the 12E8 or PHF1 antibodies. Scale bar, 20 μm. The optical density of tau phosphorylated at Ser262/Ser356 (12E8). (e) and Ser396/Ser404 (PHF1) (f) in the soma of ~30 neurons randomly chosen was analysed with the ImageJ program. Data were analysed using Student's t-test (***P0.001).",
    "ncbi_link": "FIGB: 
hNDP52: 10241"
  },
  {
    "caption": "(b) Naive cortical cells were co-transfected with the plasmids expressing HA-hNDP52 or HA-tagged domain-deleted mutants of human NDP52 together with GFP-tau. Twenty-four hours later, cell lysates were prepared and transfected tau was immunoprecipitated and blots probed for both the HA-hNDP52 constructs and GFP-tau. Homogenates (input) used for co-immunoprecipitation were analysed by immunoblotting using anti-HA or a polyclonal tau-specific antibody (Tau).",
    "ncbi_link": "hNDP52: 10241
tau: 17762"
  },
  {
    "caption": "(d,e) CN1.4 cortical cells were transfected with the mock or HA-mNDP52 plasmid (d) or with mNDP52 siRNA or scramble RNA as a control (e). The cells transfected with siRNA or scramble RNA were treated with SFN (10 μM) for 24 h. The levels of tau phosphorylated at Ser262/Ser356 and Ser396/Ser404 were analysed by immunoblotting using 12E8 and PHF1 antibodies, respectively. Total tau was detected with a polyclonal tau-specific antibody (Tau). The relative molecular masses (kDa) are indicated to the left of each blot.",
    "ncbi_link": "mNDP52: 76815"
  },
  {
    "caption": "A-F (A-C) Exercise performance on a treadmill apparatus using an intense exercise (incremental speed paradigm) that relies solely on anaerobic metabolism. (D-F) Exercise performance on a treadmill apparatus using a moderate exercise (constant sub-maximal speed) that relies on the recruitment of aerobic metabolism and that is representative of endurance exercise. (A, D) Kaplan-Meier curves representing values corresponding to the percentage of mice still running at a given time point. (B, E) Median values of the time that mice ran are represented in the min to max graphical representation; 15.5 min for wild-type (WT) and 14.33 min for SOD1G86R in (B); 59.33 min for WT and 65.43 min for SOD1G86R in (E). (C, F) Mean distance run ± SEM by WT and SOD1G86R mice in (C) and by WT and SOD1G86R mice in (F).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Grip test was performed to measure mousemuscle strength at different time points during disease progression. Graph represents the mean of percentage from initial force measured at 11 weeks ± SEM. At 13 weeks, *P = 0.03; at 14 weeks, P = 0.06; at 15 weeks, *P = 0.04 (n = 8 for WT and SOD1G86R, respectively, at 11-15 weeks, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Electromyography (EMG) recordings were performed weekly during disease development, starting from 9 weeks of age. Spontaneous electrical activity was considered as positive EMG only for peak-to-peak amplitudes > 50 μV. Left: The percentage of mice presenting with positive EMG in each age group are represented. Right: Representative examples of negative (EMG−) and positive (EMG+) electromyography profiles (n = 10 for WT and SOD1G86R, respectively, at 9-13 weeks and n = 8 and 7 for WT and SOD1G86R, respectively, at 15 weeks).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of denervation markers AChR (subunits α and γ) and MuSK were evaluated by qPCR at the indicated ages (65 and 105 days) in tibialis anterior (upper panels) and soleus (lower panels) of WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from age-matched WT (n > 5). ***P-values versus WT: < 0.0001 for AChRα, AChRγ, and MuSK in tibialis anterior; and **P-values versus WT: 0.001 for AChRα, and ***P-values versus WT: 0.0007 for AChRγ, 0.0002 for MuSK in soleus (n=7 and 8 for WT and SOD1G86R, respectively, at 65 days; n = 5 and 6 for WT and SOD1G86R, respectively, at 105 days; two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "AChRα: 11435
AChRγ: 11449
MuSK: 18198
SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of muscle atrophy markers MuRF1 and Atg-1 were measured by qPCR at the indicated ages (65 and 105 days) in tibialis anterior (upper panels) and soleus (lower panels). Graphs represent mean fold change ± SEM from age-matched WT. ***P-values versus WT: < 0.0001 for MuRF1 and Atg-1 in tibialis anterior; and **P-values versus WT: 0.007 for MuRF1 and P = 0.006 for Atg-1 in soleus (n = 7 and 8 for WT and SOD1G86R, respectively, at 65 days, n = 5 and 6 for WT and SOD1G86R, respectively, at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "SOD1: 20655
MuRF1: 433766
Atg-1: 22241"
  },
  {
    "caption": "Enzymatic activity of phosphofructokinase in whole tibialis anterior muscle cytosolic homogenates is expressed as mean fold change ± SEM from age-matched WT at 65 days of age *P = 0.016 (WT n = 6, SOD1G86Rn = 7) and 105 days of age ***P < 0.0001 (n = 5/genotype), two-way ANOVA followed by Fisher's LSD post hoc test. Data shown are representative of two independent experiments having similar results.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Left: Representative microphotographs of PAS staining from WT and SOD1G86R tibialis anterior cross-sections at 65 and 105 days of age showing glycogen-negative (light pink) and glycogen-positive (dark pink) fibers. Scale bar: 200 μm. Right: Quantification of glycogen-negative (−) and glycogen-positive (+) fibers at 65 and 105 days of age. For (−) fibers: **P-values versus WT: 0.0026 at 65 days and 0.0074 at 105 days, for (+) fibers: ##P-values versus WT: 0.0025 at 65 days and 0.0073 at 105 days (n = 5/genotype at 65 days and n = 4/genotype at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of Pdk4 and Pdk2 evaluated by qPCR at the indicated ages in tibialis anterior of WT and SOD1G86R mice. Graphs represent mean fold change ± from age-matched WT. Pdk4: **P-values versus WT: 0.014 at 65 days and 0.018 at 105 days; Pdk2: ***P-value versus WT < 0.0001 at 105 days. n = 7 and 8 for WT and SOD1G86R, respectively, at 65 days; n = 5/genotype at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test.",
    "ncbi_link": "Pdk2: 18604
Pdk4: 27273
SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of genes involved in lipid handling evaluated by qPCR at the indicated ages in tibialis anterior of WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from age-matched WT. P-values versus WT: Lpl **P = 0.0009, Cd36 *P = 0.051, Acsf2 ***P < 0.0001 at 65 days, **P = 0.0059 at 105 days and Cpt-1β **P = 0.01 at 65 days and *P = 0.02 at 105 days (n = 6 and 7 for WT and SOD1G86R, respectively, at 65 days; n = 10 and 8 for WT and SOD1G86R, respectively, at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "Acsf2: 264895
Cd36: 12491
Cpt-1β: 12895
Lpl: 16956
SOD1: 20655"
  },
  {
    "caption": "Relative levels of (left) ATP and (right) NADH and NAD+ measured in total tibialis anterior homogenates of WT and SOD1G86R mice. Left: Graphs represent mean fold change ± SEM in ATP from age-matched WT. **P = 0.002 (n = 9 and 12 for WT and SOD1G86R, respectively, at 65 days; n = 10/genotype at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test). Right: The amounts of NADH and NAD+ relative to protein content in whole tibialis anterior homogenates are represented as mean ± SEM. *P = 0.027 and **P = 0.001 (n = 5, Student's t-test).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "A-D Relative mRNA levels of (A) Pparß/δ, (B) Foxo1, (C) citrate synthase, and (D) Pgc-1α were evaluated by qPCR at the indicated ages in tibialis anterior of WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from age-matched WT. P-values versus WT: Pparβ/δ **P = 0.0016 at 65 days; Foxo1 ***P = 0.0001 at 105 days, citrate synthase ***P < 0.0001 at 105 days, Pgc-1α *P = 0.0104 at 105 days (n = 7 and 8 for WT and SOD1G86R, respectively, at 65 days; n = 5/genotype at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "citrate synthase: 12974
Foxo1: 56458
Pparß/δ: 19015
Pparβ/δ: 19015
Pgc-1α: 10891
SOD1: 20655"
  },
  {
    "caption": "F Relative mRNA levels of ERRα, Mfn2, and Nrf1 were evaluated by qPCR at the indicated ages in tibialis anterior of WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from age-matched WT. P-values versus WT: ERRα ***P < 0.0001, Mfn2 **P = 0.002 and Nrf1 **P = 0.009 (n = 6-7 and 7-8 for WT and SOD1G86R, respectively, at 65 days; n = 5 and 6 for WT and SOD1G86R, respectively, at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "ERRα: 26379
Mfn2: 170731
Nrf1: 18181
SOD1: 20655"
  },
  {
    "caption": "Mitochondrial DNA (mtDNA) was quantified using qPCR. Relative mtDNA levels are expressed as the ratio between mitochondrial-encoded gene Cox1 and the nuclear-encoded gene cyclophilin A. Graphs represent mean fold change ± SEM from age-matched WT for tibialis anterior (left panel) and soleus (right panel) of WT and SOD1G86R mice. ***P < 0.0001 (n = 5 and 4 for WT and SOD1G86R, respectively, at 65 days; n = 6/genotype at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "Cox1: 
cyclophilin A: 
SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of Gpx1 were measured by qPCR at the indicated ages in tibialis anterior (left panel) and soleus (right panel) of WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from age-matched WT. ***P < 0.0001 (n = 7 and 8 for WT and SOD1G86R, respectively, at 65 days; n = 9 and 8 for WT and SOD1G86R, respectively, at 105 days, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "Gpx1: 14775
SOD1: 20655"
  },
  {
    "caption": "A-I Relative mRNA levels of (A) Pdk4, (B) Pparβ/δ, (C) Foxo1, (D) Pfk1, (E) Acsf2, (F) citrate synthase, (G) PGC-1α, (H) Mfn2, and (I) Gpx1 were evaluated by qPCR in tibialis anterior of control (CT) or DCA-treated (DCA) WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from CT WT group. P-values versus WT: Pdk4 ***P = 0.002 and ##P = 0.0039, Pparβ/δ #P = 0.0178, Foxo1 **P = 0.0033 and ##P = 0.0038, Pfk1 ***P = 0.0002 and ##P = 0.0080, Acsf2 *P = 0.0437, citrate synthase ###P = 0.0004, Pgc-1α **P = 0.0084 and ###P = 0.0009, Mfn2 *P = 0.0272, $P = 0.0145 and ###P = 0.0002 and Gpx1 ***P < 0.0001 and ###P < 0.0001 (n = 9/genotype in CT groups, n = 9 and 8 for WT and SOD1G86R, respectively, in DCA group, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "Acsf2: 264895
citrate synthase: 12974
Foxo1: 56458
Gpx1: 14775
Mfn2: 170731
Pdk4: 27273
Pfk1: 18642
Pparβ/δ: 19015
PGC-1α: 10891
Pgc-1α: 10891
SOD1: 20655"
  },
  {
    "caption": "Grip strength is represented as mean of percent from T0 for each experimental group ± SEM. ##P = 0.0045 and ***P = 0.0003 (n = 9/genotype in CT groups, n = 9 and 8 for WT and SOD1G86R, respectively, in DCA group, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "Relative mRNA levels of muscular atrophy markers Murf1 and Atg-1 were measured by qPCR in tibialis anterior of control (CT) or DCA-treated (DCA) WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from CT WT group. **P = 0.0079 and ***P = 0.0018 (n = 9/genotype in CT groups, n = 9 and 8 for WT and SOD1G86R, respectively, in DCA group, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "SOD1: 20655
Murf1: 433766
Atg-1: 22241"
  },
  {
    "caption": "Relative mRNA levels of denervation markers AChRα, AChRγ, and MuSK were measured by qPCR in tibialis anterior of control (CT) or DCA-treated (DCA) WT and SOD1G86R mice. Graphs represent mean fold change ± SEM from CT WT group. **P = 0.015 for AChRα, #P = 0.028 and **P = 0.074 for AChRγ, #P = 0.042 and **P = 0.0029 for MuSK (n = 9/genotype in CT groups, n = 9 and 8 for WT and SOD1G86R, respectively, in DCA group, two-way ANOVA followed by Fisher's LSD post hoc test).",
    "ncbi_link": "AChRα: 11435
AChRγ: 11449
MuSK: 18198
SOD1: 20655"
  },
  {
    "caption": "Relative mRNA expression of PGC1α and PLIN5 in GAS muscles of WT and DKO mice (n=3 for PGC1α analysis; n=5 for PLIN5 analysis).",
    "ncbi_link": "PLIN5: 66968
PGC1α: 19017"
  },
  {
    "caption": "Relative mRNA expression of PGC1α and PLIN5 in C2C12 cells transfected with miR-183 and miR-96 agomirs (Ago-183/96) or antagomirs (Ant-183/96) (n=3).",
    "ncbi_link": "Ago-183: 
agomirs: 
Ant-183: 
antagomirs: 
miR-183: 387178
miR-96: 723886
PLIN5: 66968
PGC1α: 19017"
  },
  {
    "caption": "Mitochondrial respiration profile of C2C12 cells transfected with Ago-183/96 (J) or Ant-183/96 (K). Cellular oxygen consumption rate (OCR) was measured in real time and corresponding basal and maximal respiration were analyzed by overall OCR (n=3 or 4 per group).",
    "ncbi_link": "Ago-183: 
Ant-183: "
  },
  {
    "caption": "Western blot analysis of FoxO1, PDK4, p-PDHA1 and PDHA1 in GAS muscles of WT and DKO mice. Western blot analysis of FoxO1, PDK4, p-PDHA1 and PDHA1 in C2C12 cells transfected with Ago-183/96 (left) or Ant-183/96 (right).",
    "ncbi_link": "Ago-183: 
Ant-183: "
  },
  {
    "caption": "Western blot analysis of HSL and ATGL in GAS muscles of WT and DKO mice. Western blot analysis of HSL and ATGL in C2C12 cells transfected with Ago-183/96 (left) or Ant-183/96 (right).",
    "ncbi_link": "Ago-183: 
Ant-183: "
  },
  {
    "caption": "LD area per cell was quantified at the indicated time points to measure LD turnover in C2C12 myocytes transfected with agomiR-183/96 (N) or antagomir-183/96 (P) stained with Nile red (n=5). Representative immunofluorescence images of lipid droplets in C2C12 cells transfected with agomiR-183/96 (O) or antagomir-183/96 (Q). Scale bars: 5 μm.",
    "ncbi_link": "agomiR-183: 
antagomir-183: "
  },
  {
    "caption": "Relative expression of miR-183 and miR-96 in C2C12 myocytes transfected with miR-183 or miR-96 agomir (left) (n=3). Relative mRNA expression of FoxO1 and PDK4 in C2C12 cells treated with Ago-183 or Ago-96 (right) (n=3). Western blot analysis of FoxO1 and PDK4 in C2C12 cells treated with Ago-183 or Ago-96. Relative expression of miR-183 and miR-96 in C2C12 myocytes transfected with miR-183 or miR-96 antagomir (left) (n=3). Relative mRNA expression of FoxO1 and PDK4 in C2C12 cells treated with Ant-183 or Ant-96 (right) (n=3). Western blot analysis of FoxO1 and PDK4 in C2C12 cells treated with Ant-183 or Ant-96.",
    "ncbi_link": "Ago-183: 
Ago-96: 
agomir: 
Ant-183: 
Ant-96: 
antagomir: 
FoxO1: 56458
miR-183: 387178
miR-96: 723886
PDK4: 27273"
  },
  {
    "caption": "Relative mRNA expression (I, left) and western blot analysis (J, top) of ATGL in C2C12 cells transfected with agomir for miR-183 (Ago-183) or miR-96 (Ago-96). Relative mRNA expression (I, right) and western blot analysis (J, bottom) of ATGL in C2C12 cells transfected with antagomir for miR-183 (Ant-183) or miR-96 (Ant-96). (n=5 per group for RT-PCR analysis)",
    "ncbi_link": "Ago-183: 
Ago-96: 
agomir: 
Ant-183: 
Ant-96: 
antagomir: 
miR-183: 387178
miR-96: 723886
ATGL: 66853"
  },
  {
    "caption": "Relative mRNA expression of ATGL, PGC1α, PLIN5, and HSL in C2C12 cells transfected with ATGL (n=5).",
    "ncbi_link": "HSL: 16890
PLIN5: 66968
ATGL: 66853
PGC1α: 19017"
  },
  {
    "caption": "Relative mRNA expression of PGC1α, PLIN5, and HSL in C2C12 cells transfected with Ant-183/96 and siRNA of PPARδ (siPPARδ).",
    "ncbi_link": "Ant-183: 
HSL: 16890
PLIN5: 66968
PPARδ: 19015
PGC1α: 19017"
  },
  {
    "caption": "Relative mRNA expression of ATGL, HSL, and PLIN5 in GAS and SOL muscles of C57 BL/6 mice (n=3). Western blot analysis of ATGL, HSL, and PLIN5 in GAS and SOL muscles of C57 BL/6 mice.",
    "ncbi_link": "HSL: 16890
PLIN5: 66968
ATGL: 66853"
  },
  {
    "caption": "Relative mRNA expression of ATGL, HSL, and PLIN5 in GAS muscles of C57 BL/6 mice fed with HFD for 2 months (n=5). Western blot analysis of ATGL, HSL, and PLIN5 in GAS muscles of C57 BL/6 mice fed with HFD for 2 months.",
    "ncbi_link": "HSL: 16890
PLIN5: 66968
ATGL: 66853"
  },
  {
    "caption": "(A) Overexpression of RNF26 promoted polyubiquitination of MITA. The 293 cells (5×106) were transfected with Flag-MITA (5 µg) and HA-Ub (1 µg) together with a control or RNF26 expression plasmid (0.5, 1, 2 µg). Twenty-four hours after transfection, cells were subjected to immunoprecipitation (IP) under denatured conditions with anti-Flag and the immunoprecipitates were analyzed by immunoblots with anti-HA (upper panel) or anti-Flag (lower panel). The whole cell lysates were analyzed by immunoblots with anti-HA (upper panel), anti-Flag (middle panel) and anti-RNF26 (bottom panel). Ub, ubiquitin.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(B) RNF26-mediated polyubiquitination of MITA depends on the enzymatic activity of RNF26. The 293 cells (5×106) were transfected with Flag-MITA (5 µg) and HA-Ub (1 µg) together with RNF26 or its mutants (1 µg each). IP under denatured conditions and ubiquitination assay was performed as described in (A).",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(D) RNF26 but not its enzymatic inactive mutants targeted MITA for polyubiquitination in vitro. MITA, RNF26 and its mutants were obtained by in vitro transcription and translation. Biotin-Ub, E1, UbcH5 and MITA were incubated with RNF26 or its mutants, followed by ubiquitination and immunoblot analysis as described in (C). All experiments were repeated for at least three times with similar results.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(A) RNF26 mediated polyubiquitination of MITA at K150. The 293 cells (5×106) were transfected with HA-Ub (1 µg) and RNF26 (1 µg) together with Flag-MITA or the indicated mutants (5 µg each). Twenty-four hours after transfection, cells were subjected IP under denatured conditions with anti-Flag and immunoprecipitates were analyzed by immunoblots with anti-HA (upper panel) or anti-Flag (lower panel). The whole cell lysates were analyzed by immunoblots with anti-Flag or anti-RNF26 as indicated.",
    "ncbi_link": "RNF26: 79102
MITA: 340061"
  },
  {
    "caption": "B) RNF26 targeted MITA for polyubiquitination at K150 in vitro. RNF26, MITA and its mutants were obtained by in vitro transcription and translation. Biotin-Ub, E1, UbcH5 and RNF26 were incubated with MITA or its mutants. The ubiquitination of MITA was examined by immunoblot analysis with HRP-streptavidin (top panel). The inputs of RNF26 and MITA were analyzed by immunoblots with anti-MITA and anti-RNF26 (bottom panels). All experiments were repeated for at least three times with similar results.",
    "ncbi_link": "MITA: 340061"
  },
  {
    "caption": "(A and B) RNF26 targeted MITA for K11-linked polyubiquitination. The 293 cells (5×106) were transfected with Flag-MITA (5 µg) and RNF26 (1 µg) together with HA-Ub or its mutants (1 µg each). Twenty-four hours after transfection, cells were subjected for IP under denatured conditions with limited amount of anti-Flag (0.5 µg) so that equal amount of Flag-MITA is pulled down. The immunoprecipitates were analyzed by immunoblots with anti-HA (upper panel) or anti-Flag (lower panel). The whole cell lysates were analyzed by immunoblots with anti-Flag or anti-RNF26 as indicated. Ub-AKR, all lysine residues of ubiquitin were mutated to arginine.",
    "ncbi_link": "RNF26: 79102
MITA: 340061
Ub: 7316///7314///6233///7311"
  },
  {
    "caption": "(C) Effects of RNF26-RNAi plasmids on the expression of RNF26. In the upper panels, the 293 cells (1×106) were transfected with the expression plasmids for RNF26-Flag (0.5 µg) and HA-β-actin (0.1 µg) together with the indicated RNAi plasmids (1 µg each). Twenty-four hours after transfection, whole cell lysates were analyzed by immunoblots with anti-Flag or anti-HA. In the lower panels, 293 cells were transduced with a control or RNF26-RNAi by retrovirus mediated gene transfer. Cells (1×106) were lysed and whole cell lysates were analyzed by immunoblots with anti-RNF26 or anti-β-actin.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(D) Immunoblot analysis of Flag-tagged ubiquitin expression in THP-1 cells stably transfected with Flag-Ub-K11O plasmid. Whole cell lysates of THP-1-Flag-Ub-K11O-RNF26-RNAi and control cells (1×106) were analyzed by immunoblots with antibodies against the indicated proteins. RNF26-RNAi #1 was used here and in the following experiments if not noted.",
    "ncbi_link": "RNF26: 79102
Ub: 7316///7314///7311///6233"
  },
  {
    "caption": "(E and F) Effects of RNF26 knockdown on virus-induced K11-linked polyubiquitination of endogenous MITA. In (E), THP-1-Flag-Ub-K11O-RNF26-RNAi or control cells (2×107) were infected with SeV or HSV-1 for the indicated time points or left uninfected followed by IP under denatured conditions with anti-MITA. The immunoprecipitates were analyzed by immunoblots with anti-Flag (upper panels) or anti-MITA (lower panels). The whole cell lysates were analyzed by immunoblots with antibodies against the indicated cellular or viral proteins. In (F), 293-HA-Ub-K11O cells (2×107) were transfected with a control or RNF26-RNAi plasmid (10 µg each). Twelve hours after transfection, puromycin (1 µg/mL) was added into the culture medium. The cells were selected for twenty-four hours and infected with SeV or left uninfected for the indicated time points followed by IP under denatured conditions and immunoblot analysis as in (E). All experiments were repeated for at least three times with similar results.",
    "ncbi_link": "RNF26: 79102
Ub: 7316///7314///7311///6233"
  },
  {
    "caption": "A) Effects of RNF26 knockdown on virus-induced polyubiquitination of endogenous MITA. The THP-1-RNF26-RNAi or control cells (2×107) were infected with SeV or HSV-1 for the indicated time points or left uninfected. Cell lysates were subjected to IP under denatured conditions with anti-MITA and the immunoprecipitates were analyzed by immunoblots with anti-Ub(K48) (upper panel), anti-Ub(K63) (middle panel) or anti-MITA (lower panel). The whole cell lysates were analyzed by immunoblots with antibodies against the indicated proteins.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(B) Effects of RNF5 knockdown on virus-induced K11-linked polyubiquitination of endogenous MITA. The 293-HA-Ub-K11O cells (2×107) were transfected with the indicated RNAi plasmid (10 µg each). Twelve hours after transfection, the cells were selected with puromycin (1 µg/mL) for twenty-four hours and infected with SeV for the indicated time points or left uninfected. Cell lysates were subjected to IP under denatured conditions with anti-MITA and the immunoprecipitates were analyzed by immunoblots with anti-HA (upper panel) or anti-MITA (lower panel). The whole cell lysates were analyzed by immunoblots with antibodies against the indicated antibodies.",
    "ncbi_link": "RNF5: 6048"
  },
  {
    "caption": "(C) RNF26 and RNF5 competed with each other on MITA polyubiquitination. The 293 cells (5×106) were transfected with MITA (5 µg), Flag-Ub-K48O and HA-Ub-K11O (1 µg each) together with indicated amount of RNF26 and RNF5. Twenty-four hours after transfection, cell lysates were subjected to IP under denatured conditions with anti-MITA and the immunoprecipitates were analyzed by immunoblots with anti-Flag (upper panel), anti-HA (middle panel) or anti-MITA (lower panel). The whole cell lysates were analyzed by immunoblots with antibodies against the indicated proteins.",
    "ncbi_link": "RNF26: 79102
RNF5: 6048
MITA: 340061
Ub: 7316///7314///7311///6233"
  },
  {
    "caption": "(D) Effects of RNF26 knockdown on virus-triggered MITA degradation. The THP-1-RNF26-RNAi or control cells (1×106) were infected with SeV or HSV-1 for the indicated time points or left uninfected. Cells were lysed and whole cell lysates were analyzed by immunoblots with antibodies against the indicated proteins (upper immunoblots). The relative protein levels of MITA in reference to β-actin were analyzed by Quantity One program and data shown are mean ± S.D. of three independent experiments (lower histographs).",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(A) Effects of RNF26 knockdown on SeV-triggered activation of the IFN-β promoter. The 293 cells (2×105) were transfected with the IFN-β promoter reporter (0.1 µg) and the indicated RNAi plasmid (0.5 µg each). Thirty hours after transfection, cells were infected with SeV for 12 hours or left uninfected before reporter assays were performed.",
    "ncbi_link": "IFN-β: 3456
RNF26: 79102"
  },
  {
    "caption": "(B and C) Effects of RNF26 knockdown on virus-triggered induction of IFN-β in THP-1 cells. The THP-1-RNF26-RNAi or control cells (1×106) were infected with SeV or HSV-1 for the indicated time points or left uninfected followed by quantitative real-time PCR (B)",
    "ncbi_link": "IFN-β: 3456
RNF26: 79102"
  },
  {
    "caption": "(B and C) Effects of RNF26 knockdown on virus-triggered induction of IFN-β in THP-1 cells. The THP-1-RNF26-RNAi or control cells (1×106) were infected with SeV or HSV-1 for the indicated time points or left uninfected followed by quantitative real-time PCR (B) or ELISA analysis (C",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(D) Effects of RNF26 knockdown on virus-triggered induction of IFNB1 gene in THP-1 cells. The THP-1-RNF26-RNAi or control cells (1×106) were infected with VSV, EMCV or ECTV for the indicated time points or left uninfected before quantitative real-time PCR analysis was performed as in (B).",
    "ncbi_link": "IFNB1: 3456
RNF26: 79102"
  },
  {
    "caption": "(E and F) Effects of RNF26 knockdown on virus-triggered induction of TNFα in THP-1 cells. The THP-1-RNF26-RNAi or control cells (1×106) were infected with SeV or HSV-1 for the indicated time points or left uninfected followed by quantitative real-time PCR (E) and ELISA analysis (F).",
    "ncbi_link": "RNF26: 79102
TNFα: 7124"
  },
  {
    "caption": "(G) Effects of RNF26 knockdown on virus-triggered phosphorylation of TBK1, IRF3 and IκBα. The THP-1-RNF26-RNAi or control cells (1×106) were infected with SeV or HSV-1 for the indicated time points or left uninfected, whole cell lysates were analyzed by immunoblots with anti-p-TBK1, anti-TBK1, anti-p-IRF3, anti-IRF3, anti-p-IκBα, anti-IκBα, anti-RNF26 or anti-β-actin as indicated. All experiments were repeated for at least three times with similar results. The bar graphs show mean ± S.D. (n = 3) of a representative experiment performed in triplicate.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "A) Effects of RNF26 knockdown on IRF3 level. In the left panel, whole cell lysates of THP-1-RNF26-RNAi or control cells (1×106) were analyzed by immunoblots with the indicated antibodies. In the right panel, cells (1×106) were subjected to quantitative real-time PCR analysis.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "B) Effects of RNF26 on IRF3 stability. The 293 cells (1×106) were transfected with HA-IRF3 (0.5 µg) and HA-β-actin (0.1 µg) together with RNF26 or its mutant (0.3 µg each). Twenty-four hours later, whole cell lysates were analyzed by immunoblots with anti-HA or anti-RNF26.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "(C) Effects of RNF26 and its mutant on SeV-triggered activation of the IFN-β promoter. The 293 cells (2×105) were transfected with the IFN-β promoter reporter (0.1 µg) and RNF26 or its mutant (0.1 µg each). Twenty hours after transfection, cells were infected with SeV for 12 hours or left uninfected before reporter assays were performed.",
    "ncbi_link": "IFN-β: 3456
RNF26: 79102"
  },
  {
    "caption": "(D) Effects of RNF26 on IRF3 ubiquitination. The 293 cells (5×106) were transfected with Flag-IRF3 (5 µg) and RNF26 (1 µg) together with HA-Ub or its mutants (1 µg each). Eighteen hours after transfection, 3-MA (500 ng/mL) was added into culture medium for 4 hours to protect IRF3 from autophagosomal degradation during the experiment. The cell lysates were subjected to IP under denatured conditions with anti-Flag and the immunoprecipitates were analyzed by immunoblots with anti-HA (upper panels) or anti-Flag (lower panels). The whole cell lysates were analyzed by immunoblots with anti-Flag or anti-RNF26 as indicated.",
    "ncbi_link": "IRF3: Q14653///3661
RNF26: Q9BY78///79102
Ub: 7316///7314///7311///6233"
  },
  {
    "caption": "(E) Effects of inhibitors on RNF26-mediated destabilization of IRF3. The 293 cells (1×106) were transfected with the indicated plasmids as described in (B). Eighteen hours after transfection, 3-MA (500 ng/mL), NH4Cl (25 mM) or MG132 (100 µM) was added into culture medium for four hours. Whole cell lysates were analyzed by immunoblots with anti-HA or anti-RNF26.",
    "ncbi_link": "IRF3: 3661
RNF26: 79102"
  },
  {
    "caption": "(F) Effects of ATG12 knockdown on RNF26-mediated destabilization of IRF3. The 293-ATG12-RNAi or control cells (1×106) were transfected with the indicated plasmids. Twenty-four hours later, whole cell lysates were analyzed by immunoblots with anti-HA, anti-RNF26 or anti-ATG12 as indicated. All experiments were repeated for at least three times with similar results. The bar graphs show mean ± S.D. (n = 3) of a representative experiment performed in triplicate.",
    "ncbi_link": "ATG12: 9140
IRF3: 3661
RNF26: 79102"
  },
  {
    "caption": "C57BL/6, SHP-KO, and FGF15-KO or littermate mice  were fasted  overnight and then   re-fed  for 6 (A-C) Levels of the indicated proteins detected by IB  in (A) liver  and intestinal  extracts from C57BL/6 mice  and in intestinal  extracts from (B) C57BL/6 or SHP-KO mice or (C) FGF15-KO mice or littermates. Band quantitation was done using Image J, and the LC3 II/I ratio and p62/actin and lamp1/actin  ratios are shown at the right. (A-C) The mean and standard deviation (SD) are plotted. Statistical significance was determined by (A) two-tailed Student's t-tests or (B, C) two-way ANOVA with the Tukey post-test. P-values are indicated (n=3 mice).",
    "ncbi_link": "FGF15: 14170
SHP: 23957"
  },
  {
    "caption": "C57BL/6, SHP-KO, and FGF15-KO or littermate mice  as indicated were fasted   for 12 h and then, re-fed   for 6 h. levels of the indicated proteins in intestinal  extracts from (B) C57BL/6 and SHP-KO mice  or (D) FGF15-KO mice and littermates with quantitation of the bands at right. , (B, D) n=3 mice. The mean and SD are plotted. Statistical significance was determined by two-way ANOVA with the Tukey post-test P-values are indicated",
    "ncbi_link": "FGF15: 14170
SHP: 23957"
  },
  {
    "caption": "(G) HT29 cells were transfected with GFP-LC3  and with SHP  siRNA or SHP  expression plasmids and incubated in serum-free medium containing 200 μM  oleic acid for 6 h followed by treatment with 50 ng/ml FGF19  for 6 h The control group (Veh) was treated with vehicle for FGF19, control plasmid DNA, and scrambled siRNA. The FGF19  groups were treated with control DNA or SHP  expression plasmid or SHP  siRNA or control scrambled siRNA as indicated. Cells were imaged by confocal microscopy (Zeiss, LSM700). GFP-LC3  puncta were counted and the number of puncta/cell is shown at right (n = 20). Scale bar, 10 μm. G, The mean and SD are plotted. Statistical significance was determined by (G) one-way ANOVA with the Tukey post-test. P-values are indicated",
    "ncbi_link": "GFP: 
LC3: 67443///66734
SHP: 8431"
  },
  {
    "caption": "(I) HT29  cells were transfected with Lamp1  siRNA or scrambled siRNA and 48 h later were treated with 50 ng/ml FGF19  for the indicated times. ApoB48  and actin  levels were determined by IB  (n=2 culture plates).",
    "ncbi_link": "Lamp1: 3916"
  },
  {
    "caption": "(A) HT29  cells were transfected with GFP-LC3  and with Atg7  siRNA or control scrambled RNA (siCtl) and incubated in serum-free medium containing 200 μM oleic acid  for 6 h followed by treatment with 50 ng/ml FGF19  for 6 h The control group (Veh) was treated with vehicle for FGF19 and control siRNA. The FGF19  groups were treated with Atg7  siRNA or scrambled siRNA as indicated. Cells were imaged by  confocal microscopy (Zeiss, LSM700). GFP-LC3  puncta were counted and the number of puncta/cell is shown at right (n = 20). Scale bar, 20 μm. The mean and SD are plotted. Statistical significance was determined by one-way ANOVA with the Tukey post-test. P-values are indicated.",
    "ncbi_link": "GFP: 
Atg7: 10533
LC3: 67443///66734"
  },
  {
    "caption": "(B) HT29  cells were transfected with Atg7 siRNA or control scrambled siRNA and 48 h later were treated with 50 ng/ml FGF19  for 12 h. LC3  and actin   levels in cell extracts determined by IB  (n=3 culture plates).",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "D) HT29  cells were transfected with Atg7  siRNA or control scrambled siRNA (siCtl) for 48 h and then treated with  oleic acid for 6 h followed by treatment with 50 ng/ml FGF19  for 12 h. (D) ApoB48  and actin  levels in cell extracts determined by IB. Bands were quantified and the LC3-II/LC3-I ratio is shown at the right (n=3 culture plates). The mean and SD are plotted. Statistical significance was determined by one-way ANOVA with the Tukey post-test. P-values are indicated.",
    "ncbi_link": "Atg7: 10533"
  },
  {
    "caption": "(F, G) Protein levels detected by IB  of ULK1  and ATGL  in intestinal  extracts from (F) C57BL/6 and SHP-KO mice  or (G) FGF15-KO mice or littermates re-fed for 6 h after fasting   overnight (n=3 mice).",
    "ncbi_link": "FGF15: 14170
SHP: 23957"
  },
  {
    "caption": "(A) HT29  cells were transfected with GFP-LC3  and with Tfeb  siRNA or Tfeb  expression plasmids and incubated in serum-free medium containing 200 μM oleic acid for 6 h followed by treatment with 50 ng/ml FGF19  for 6 h The control group (Veh) was treated with vehicle for FGF19  and transfected with control plasmid DNA and scrambled siRNA. The FGF19  groups were treated with control DNA or TFEB  expression plasmid or with Tfeb  siRNA or scrambled siRNA as indicated. Cells were imaged by  confocal microscopy (Zeiss, LSM700). GFP-LC3  puncta were counted and the number of puncta/cell is shown at right (n = 20 cells). Scale bar, 10 μm. (A, The mean and SD are plotted. Statistical significance was determined by (A) one-way ANOVA with the Tukey post-test, P-values are indicated.",
    "ncbi_link": "GFP: 
LC3: 67443///66734
Tfeb: 7942
TFEB: 7942"
  },
  {
    "caption": "(B) HT29  cells were transfected with siRNA for Tfeb  (siTFEB) or control scrambled siRNA (siCtl), followed 48 h later by treatment with FGF19  or vehicle with or without 100 nM  bafilomycin A1  (BAF) for 12 h. Levels of the indicated proteins determined by IB.  LC3 II/I and p62/actin  ratios are shown at the right (n=3-4 culture plates). B, The mean and SD are plotted. Statistical significance was determined by (B) two-way ANOVA with the Tukey post-test, P-values are indicated.",
    "ncbi_link": "Tfeb: 7942
TFEB: 7942"
  },
  {
    "caption": "(C) HT29  cells were transfected with siRNA for TFEB  (siTFEB) or control RNA (siCtl), followed 48 h later by treatment with FGF19  or vehicle for 12 h. Protein levels detected by IB  of ULK1  and ATGL  (n=3 culture plates).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(E) HT29  cells were transfected with siRNA for Tfeb  (siTFEB) or scrambled siRNA (siCtl), followed 48 h later by treatment with FGF19  or vehicle for 12 h. ApoB48  and actin  levels in cell extracts determined by IB  (n=3 culture plates).",
    "ncbi_link": "Tfeb: 7942
TFEB: 7942"
  },
  {
    "caption": "B) FGF15-KO mice  or littermates (B) were  re-fed  for 6 h after fasting   overnight. the indicated proteins were detected by IB  (n=2 mice). TBLN  indicates tubulin.",
    "ncbi_link": "FGF15: 14170"
  },
  {
    "caption": "FGF15-KO mice  or littermates were fasted  overnight and re-fed  for the indicated times. (C) The nuclear  fraction was isolated and the nuclear  levels of TFEB, SHP, and LAMIN  were determined by IB.",
    "ncbi_link": "FGF15: 14170"
  },
  {
    "caption": "FGF15-KO mice  or littermates were fasted  overnight and  re-fed  for the indicated times. (D) Levels of LC3, p62, and actin in cell extracts were determined by IB.",
    "ncbi_link": "FGF15: 14170"
  },
  {
    "caption": "(F) FGF15-KO mice  or littermates were re-fed  for 0, 2, or 3 h after fasting  overnight. The indicated proteins in intestinal  extracts were detected by IB  (n=2 mice).",
    "ncbi_link": "FGF15: 14170"
  },
  {
    "caption": "(G) HT29  cells were transfected with expression plasmids for flag-tagged TFEB  or its mutants as indicated and 24 h later, cells were treated with FGF19 (50 ng/ml) for 12 h. ∆CT indicates the TFEB  mutant with a C-terminal deletion of 15 amino acids. The indicated proteins were detected by IB (n=3 culture plates).",
    "ncbi_link": "flag: 
TFEB: 7942"
  },
  {
    "caption": "A  Hormone-inducible  nuclear  import assay, representative still images of GCR2-EGFP2-TDP-43 Wt, 12D and 12A before and during import triggered by addition of dexamethasone. Images were live  recorded by spinning disc confocal microscopy. Bar, 20 µm. B Quantification of the  hormone-inducible  nuclear import  measured during a total  time course  of 50 min. Values represent the mean fluorescence intensity of GCR2-EGFP2-TDP-43 in the  cytoplasm for three independent replicates ± SEM (≥ 42 cells per condition).",
    "ncbi_link": "EGFP: 
GCR: 2908
TDP-43: 23435"
  },
  {
    "caption": "C Phosphomimetic 12D  TDP-43 is competent in autoregulating  TDP-43 expression. SDS-PAGE followed by TDP-43 Western blot showing downregulation of endogenous TDP-43 through autoregulation (60) after 48 h expression of Wt, 12D and 12A variants in  HeLa cells. TDP-43 was detected using rabbit anti-TDP-43 C-term antibody (Proteintech), Histone H3 (rabbit anti-Histone H3 antibody, Abcam) was visualized as a loading control. * denotes an unspecific band.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "E Splicing  analysis by RT-PCR  of known TDP-43 splice targets (SKAR  exon 3 and  Bim  exon 3) in HeLa  cells. Silencing of endogenous TDP-43 by siRNA leads to altered splice isoforms of SKAR  and Bim  (second vs. first lane). These  splicing alterations can be rescued by re-expression of TDP-43 Wt, but also 12D or 12A variants, demonstrating that phosphomimetic TDP-43 is fully competent in regulation  splicing  of these  TDP-43  splice targets. ",
    "ncbi_link": "Bim: 10018
SKAR: 84271
TDP-43: 23435"
  },
  {
    "caption": "F SG  recruitment of different  TDP-43-NLSmut variants in intact HeLa  cells in the absence of endogenous TDP-43. After TDP-43 silencing and expression of NLSmut Wt, 12D and 12A variants, SGs were induced by H2O2 treatment and  SG recruitment of TDP-43 was monitored by TDP-43 and G3BP1 immunostaining. For clarity, signals were converted to grey values in the individual channels (upper two rows). In the merge (lower row), nuclei  were stained in DAPI (turquoise), TDP-43 (green) and G3BP1 (red). Bar, 40 µm.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "H Recruitment of TDP-43 into arsenite-induced nuclear bodies (NBs) in HeLa cells. After TDP-43 silencing and expression myc-TDP-43 Wt, 12D and 12A, NBs were induced by sodium arsenite treatment and NB  recruitment of  TDP-43 was monitored by TDP-43 immunostaining. Bar, 20 µm.",
    "ncbi_link": "myc: 
TDP-43: 23435"
  },
  {
    "caption": "J Intensity profiles (right) of  TDP-43 Wt, 12D and 12A variants (green) along white lines (left). Bar, 10 µm.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "A Biochemical fractionation into  RIPA-soluble (S) and RIPA-insoluble (I) fractions to analyze solubility of the different myc-TDP-43 variants (Wt, 12D and 12A) expressed in HeLa  cells for 48 h.  TDP-43 was detected by TDP-43 Western blot (upper blot, rabbit anti-TDP-43 C-term, Proteintech) and Myc Western blot (lower blot, mouse anti-Myc 9E10). B Quantification of myc-TDP-43 variants (Wt, 12D and 12A) in (S) versus (I) fractions extracted from TDP-43 Western blots  of 4 independent replicates ± SD, plotted as S/(S+I). *p < 0.0332 by one way ANOVA with Dunnett´s multiple comparison test to Wt.",
    "ncbi_link": "myc: 
TDP-43: 23435"
  },
  {
    "caption": "D Primary  hippocampal neurons expressing  EGFP-TDP-43 Wt, 12D or 12A with additional NLS mutation. Bar, 80 µm. Right: Zoomed images of white squares (TDP-43   signal). Bar, 10 µm.",
    "ncbi_link": "EGFP: 
TDP-43: 23435"
  },
  {
    "caption": "E SG recruitment of  EGFP-TDP-43 NLS mutant variants (Wt, 12D, 12A) in primary hippocampal neurons. SG formation was induced by 1h heat shock at 42°C.  SGs  and TDP-43 were monitored by G3BP1 antibody staining and EGFP fluorescence, respectively. For clarity, signals were converted to grey values in the individual channels (first two columns). In the merge (third column), EGFP-TDP-43  shown in green, G3BP1 in red and nuclei (DAPI staining) in turquoise. Bar, 20 µm.",
    "ncbi_link": "EGFP: 
TDP-43: 23435"
  },
  {
    "caption": "A. Expression  levels of various GPI-APs in different clones of PIGG-KO HEK293 cells. Fluorescence intensities of NT5E  in PIGG-KO clones #4, #10, #17, #19 and wild type cells are 575, 910, 696, 530 and 1548 while those of EphrinA5 in clones #4, #17, #19 and wild type cells are 1431, 2080, 1868 and 3336, respectively. Data information: Each FACS  analysis was performed at least three times.",
    "ncbi_link": "PIGG: 54872"
  },
  {
    "caption": "B. Expression  levels of GPI-APs in PIGG-KO clone #19 cells stably transfected with PIGG  cDNA compared to levels in empty vector transfected cells. Fluorescence intensities  of NT5E  in PIGG  cDNA and in vector transfected cells are 1332 and 886, respectively. Data information: Each FACS  analysis was performed at least three times.",
    "ncbi_link": "PIGG: 54872"
  },
  {
    "caption": "A. Expression  levels of different GPI-APs in PIGG-KO HEK293  cells transiently co-transfected with PIGG  cDNA or empty vector. Vertical bars represent % of levels of GPI-APs expression in non-rescued PIGG-KO cells relative to those in PIGG  cDNA rescued PIGG-KO cells. Analysis was repeated 3 to 6 times and SD bars were shown.",
    "ncbi_link": "PIGG: 54872"
  },
  {
    "caption": "B. HA  tagged NTNG2  and FLAG tagged DAF  were transiently co-transfected together with PIGG  cDNA or empty vector to PIGG-KO cells and were analyzed by FACS. Fluorescence intensity levels of NTNG2  in PIGG-KO cells and in PIGG  rescued cells are 639 and 3426, while those of DAF  in PIGG-KO cells and in PIGG  rescued cells are 562 and 599, respectively. Each FACS  analysis was performed at least three times.",
    "ncbi_link": "FLAG: 
HA: 
DAF: 1604
NTNG2: 84628
PIGG: 54872"
  },
  {
    "caption": "A-C. PTEN  mRNA levels in LCM normal ovarian  surface epithelium   versus high-grade serous ovarian cancer  (HGSOC) epithelium  or normal  ovarian  stroma   versus ovarian cancer-associated stroma. Datasets; (A) GSE40595, (B) GSE38666, (C) Epithelium  only, GSE14407. Sample size (n) and p-values, (Mann-Whitney) annotated, whiskers Min-Max, line at median.",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "F. Overall survival (% patients, months) of OC patients. Highest quartile (Q4) versus combination of quartiles 1-3 (Q1+2+3), PTEN  mRNA (TCGA, OV). Median survival  (40 and 44 months), sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated. G.  Overall survival  (% patients, months) of OC patients. Highest quartile (Q4) versus combination of quartiles 1-3 (Q1+2+3), PTEN  protein. Reverse Phase Protein Array Data, TCGA OV. Median survival  (46 and 57 months), sample size (n) and p-value, Log-rank test (Mantel-Cox).",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "H. Differential abundance (x, Log Ratio between conditions; y, -Log10 q-values) of Reverse Phase Protein Array data (TCGA, OV) in patient  grouped by PTEN  mRNA, High (Q4) vs Low (Q1). Significant, blue (-Log10 q-values >1.3); AKT  signalling pathway, labelled. I. Differential abundance (x, Log Ratio between conditions; y, -Log10 q-values) of proteins in PTEN  High (Q4) vs PTEN  Low (Q1) protein samples. Reverse Phase Protein Array Data, TCGA OV. Significantly altered components in AKT  signalling pathway labelled (-Log10 q-value> 1.3).",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "A. Confocal  images (single slice) of Trp53-/- or Trp53-/-;Pten-/- (1.15) spheroids  expressing mNeonGreen-tagged (mNG) biosensors for PI(4,5)P2  (PH-PLCδ1) or PIP3  (CYTH32G/GRP1). Magnified images from boxed regions, max projection of 8 (PH-PLCδ1) or 3 (CYTH32G/GRP1) z-slices, pseudocoloured in FIRE LUT. Arrowheads: red, cell-cell contact; yellow, nucleus; green, protrusion tip. Scale bar, 7μm. Representative of 8 (Trp53-/-) or 10 (Trp53-/-;Pten-/-) spheroids  imaged across n=2 independent experiments (PH-PLCδ1) and 22 (Trp53-/-) or 23 (Trp53-/-;Pten-/-) spheroids  imaged across n=4 independent experiments (CYTH32G/GRP1). B. Intensity profiles for PH-PLCδ1  and PH-CYTH3  from spheroids  shown in (A). Protrusions measured are annotated on images in upper panels, yellow lines. Arrowheads: red, protrusion tips.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "D. Western blotting  and quantitation for S6RP  pS235/236, S6RP, GAPDH  (sample integrity control) in Trp53-/-;Pten-/- 1.15 spheroids treated with DMSO  or inhibitors annotated in (B) for 2 days. Representative of n=3 independent lysate preparations. Data, mean ± SD of pS235/236:total S6RP  ratio, normalised to DMSO. P-values, unpaired, 2-tailed t tests, as annotated.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "Quantitation of ID8 Trp53-/-;Pten-/- spheroids  treated with PI3K isoform specific inhibitors: A66  (PI3Kα), AZD8186  (PI3Kβ), AS605240  (PI3Kγ) or CAL-101 (PI3Kδ), 6hr time  intervals over 72 hrs. (I) Frequency of Spherical  and Hyper-protrusive phenotypes. Heatmap (grayscale) - phenotype proportion (z-score) in control. Heatmap (blue-red) - log2 fold change from control. P-values, bubble size (Cochran-Mantel-Haenszel test with Bonferroni adjustment). Black dot, homogenous effect across independent experiments (Breslow-Day test, Bonferroni adjustment, non-significant). N=2 independent experiments, 3-5 technical replicates/experiment.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "K. Confocal  image of Trp53-/-;Pten-/- (1.15) spheroids stained  for PI3Kβ  (green),  F-actin (magenta) and Hoechst  (grey). Magnified images from boxed regions, pseudocoloured in inverted grayscale (F-actin) or FIRE LUT (PI3Kβ). Yellow or white/black arrowheads, enrichment of F-actin  or PI3Kβ  at protrusion tips  respectively. Scale bar, 5μm. Representative of n=5 spheroids.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "A-B. Quantitation of ID8 Trp53-/-;Pten-/- 1.15 spheroids  expressing shScramble, shArf5 or shArf6, 6hr time  intervals over 72 hrs. (A) Heatmap (viridis) - area presented as mean of Z-score values, normalised to control (shScramble). (B) Frequency of Spherical  and Hyper-protrusive phenotypes. Heatmap (grayscale) - phenotype proportion (z-score) in control. Heatmap (blue-red) - log2 fold change from control. P-values, bubble size (Cochran-Mantel-Haenszel test with Bonferroni adjustment). Black dot, homogenous effect across independent experiments (Breslow-Day test, Bonferroni adjustment, non-significant). N=3 independent experiments, 4-5 technical replicates/experiment. C. Representative phase contrast images of spheroids  described in (A-B). Outlines pseudocoloured for classification (Spherical, green; Hyper-protrusive, blue). Magnified individual spheroids  from boxed regions at indicated timepoints. Arrowheads, protrusions  into ECM. Scale bars, 400μm or 17μm, as indicated.",
    "ncbi_link": "Arf5: 11844
Arf6: 11845
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "Representative confocal  images and intensity profiles of ID8 Trp53-/- and Trp53-/-;Pten-/- 1.15 cells expressing mNeonGreen  (mNG)-tagged ARF6    (green) and F-actin (magenta) at the invasive front of wounded monolayers Scale bar, 5μm. Tips  for which ARF6-mNG  and F-Actin intensity profiles were measured are annotated, ECM  to body, yellow arrow.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "Representative confocal  images and intensity profiles of ID8 Trp53-/- and Trp53-/-;Pten-/- 1.15 cells expressing mNeonGreen  (mNG)-tagged ARF6  (green) and  F-actin (magenta) in spheroids  (max. projection ~ 10 Z-slices) Scale bar, 5μm. Tips  for which ARF6-mNG  and F-Actin intensity profiles were measured are annotated, ECM  to body, yellow arrow.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "Heatmap, (J) ARF6 interactors  across genotypes. White to blue colour or blue to red, ARF6 interaction  score, Log2Fold Student's t-test Difference in LFQ intensity compared to control ID8 Trp53-/-;Pten-/- 1.15 TurboID  alone. Interactors, sorted, descending order of mean interaction. N=4 independent lysate preparations from each sub-line.",
    "ncbi_link": "TurboID: 
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "C. Western blot, β1-integrin  (ITGB1), pS473-AKT, AKT, ARF6  from deconvolved ITGB1  sgRNA-expressing cells. VCL, loading control for ITGB1, sample integrity control for other blots. Representative blots  of n=3 independent lysate preparations. D. Quantitation of (C). Data, mean ± SD for pS473-AKT:total AKT  band intensity ratio, total AKT  or ARF6  intensity, normalised to control (sgNT ID8 Trp53-/-;Pten-/- clone 1.15) cells. P-values, unpaired, two-tailed t-test.",
    "ncbi_link": "ITGB1: 16412
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "E-F. Frequency of Spherical  and Hyper-protrusive phenotypes in ID8 Trp53-/-;Pten-/- 1.15spheroids upon CRISPR-mediated KO of (E) Itgβ1  or (F) Agap1, 6hr time  intervals over 72 hrs. Heatmap (grayscale) - phenotype proportion (z-score) in control (sgNT). Heatmap (blue-red) - log2 fold change from control. P-values, bubble size (Cochran-Mantel-Haenszel test with Bonferroni adjustment). Black dot, homogenous effect across independent experiments (Breslow-Day test, Bonferroni adjustment, non-significant). N=3 independent experiments, 1-5 technical replicates/experiment.",
    "ncbi_link": "CRISPR: 
Agap1: 347722
Itgβ1: 16412
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "H. Representative confocal  images of Trp53-/- and Trp53-/-;Pten-/- clone 1.15 spheroids  expressing sgNT, sgAgap1  (sg3) or sgItgb1 (sg4), stained  for  collagen IV  (grayscale) and F-Actin (magenta). Boxed areas, basement membrane region in higher magnification. Arrowheads, Collagen IV labelling that is: well-defined, green; fragmented, yellow; absent, navy. Scale bar, 53μm. I. Quantitation of (H). Collagen IV basement membrane staining  as Defined, Fragmented, or Absent in spheroids  set up across n=3 independent experiments, 1 technical replicate/experiment, 5-9 fields imaged per technical replicate, 365 spheroids  scored in total. Data, mean ± SD of % of spheroids  in each phenotype for independent experiments, with circles representing technical replicates. Unpaired t-test, p values annotated.",
    "ncbi_link": "Agap1: 347722
Itgb1: 16412
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "C. Western blots of ID8 Trp53-/-;Pten-/- 1.15 cells expressing either sgNT or sgAgap1 (sg3) and either mNeonGreen  (mNG) or CRISPR-resistant mNG-Agap1_S or -L isoforms. Blotted  for ARF6, pS473-AKT, AKT, mNG, and VCL. VCL  is loading control for AKT, pS473-AKT  and ARF6  and sample integrity control for others. n=3 independent lysate preparations. D. Quantitation of (C). Data, mean ± SD for ARF6  and pS473/AKT  band intensity ratio, normalised to sgNT. P-values, unpaired two-tailed t-test, annotated when significant.",
    "ncbi_link": "CRISPR: 
mNeonGreen: 
mNG: 
Agap1: 347722
Agap1: 116987
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "E-F. Quantitation of ID8 Trp53-/-;Pten-/- 1.15 spheroids  treated with sgNT or AGAP1-targeting sg3 and expressing either mNG  or mNG-fusion with either isoform of AGAP1, 6 hr time  intervals over 72 hrs. (E) Heatmap (viridis) - area presented as mean of Z-score values, normalised to control (sgNT). (F) Frequency of Spherical  and Hyper-protrusive  phenotypes. Heatmap (grayscale) - phenotype proportion (z-score) in control. Heatmap (blue-red) - log2 fold change from control. P-values, bubble size (Cochran-Mantel-Haenszel test with Bonferroni adjustment). Black dot, homogenous effect across independent experiments (Breslow-Day test, Bonferroni adjustment, non-significant). N=3 independent experiments, 5-6 technical replicates/experiment.",
    "ncbi_link": "mNG: 
AGAP1: 347722
AGAP1: 116987
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "ARF6  and AGAP1   mRNA levels in LCM normal ovarian surface epithelium versus HGSOC epithelium  or normal ovarian stroma   versus OC-associated stroma. Specific datasets, sample size (n) and p-values (Mann-Whitney) annotated, whiskers Min-Max, line at median.",
    "ncbi_link": "AGAP1: 116987
ARF6: 382"
  },
  {
    "caption": "K-O. Overall survival (% patients, months; TCGA OV  dataset), of patients  grouped by low (M1) versus high (M2) levels, based on a median split, of (K) ARF6  mRNA, (L) AGAP1  mRNA, (M) AGAP1  Exon 14 percentage spliced in ratio (PSI), (N) combination of ARF6  and AGAP1  mRNA, or (O) combination of ARF6  mRNA and AGAP1  Ex14 PSI. Median survival, sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated.",
    "ncbi_link": "AGAP1: 116987
ARF6: 382"
  },
  {
    "caption": "A-B. Immunofluorescence  and confocal  imaging of Trp53-/-;Pten-/- 1.15 spheroids stained  for α5-integrin  or β1-integrin (grey or FIRE LUT), Hoechst  (blue) and F-actin (magenta). Magnified images from boxed regions shown. Arrowheads, labelling at protrusion tips. Scale bars, 5 μm. Representative of n=3 spheroids imaged. (B) Intensity profiles for integrins (grey) and  F-actin (magenta) from spheroids  in (A). Tip  measured is annotated, ECM  to body, yellow arrow, tip, white arrowhead.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "C-D. Immunofluorescence  and confocal  imaging of Trp53-/-;Pten-/- 1.15 spheroids stained  for pFAK (Y379) or pSRC Family Kinases (SFK  pY416) (grey or FIRE LUT), Hoechst  (blue) and F-actin (magenta). Magnified images from boxed regions shown. Arrowheads, positive staining. Scale bars, 5 μm. Representative of n=5 spheroids  imaged. (D) Intensity profiles for active FAK  and Src  (grey) and F-actin (magenta) from spheroids  in (C). Tip  measured is annotated, ECM  to body, yellow arrow, tip, white arrowhead.",
    "ncbi_link": "Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "E-H. Representative capture ELISA  graphs (E,G) and associated quantitation (F,H) for recycling of internalized cargoes between Trp53-/- versus Trp53-/-;Pten-/- cells or Trp53-/-;Pten-/- cells expressing shScramble versus shArf6 for active β1-integrin. Graphs shown are representative of n=2 (E) or n=3 (G) independent replicates. Data, mean (black square) ± SD for repeated experiments (large circles), 1-3 technical replicates/experiment/timepoint  (small circles), two-tailed t-test, p-values are annotated.",
    "ncbi_link": "Arf6: 11845
Pten: 19211
Trp53: 22059"
  },
  {
    "caption": "I-K. Overall survival  (% patients, months; TCGA OV  dataset) of patients  grouped into combined expression based on median mRNA split. (I) Low (red line, M1) or high (blue line, M2) expression for all mRNA, control, remaining patients  (green line), (J), same as (I), but CYTH2  Ex9 PSI, rather than total CYTH2. (K), as for (I), but PTEN  protein levels split by quantiles (red and blue, Q1+Q2,Q3, low PTEN, green Q4, high PTEN). Median survival, sample size (n) and p-value, Log-rank test (Mantel-Cox) annotated.",
    "ncbi_link": "CYTH2: 9266"
  },
  {
    "caption": "CY, but not bendamustine treatment, led to suppression of CBP, TIP60, MORF, and MSL1 in H1650 cells. Cells were treated with DMSO, bendamustine (350 μM), CY (15 μM), or SAHA (10 μM) for 6 h, and mRNA was extracted for qPCR analysis. Data represent mean ± SEM from three independent experiments, and statistical significance was determined by unpaired two-tailed t-test. ***P < 0.01.",
    "ncbi_link": "CBP: 1387
TIP60: 10524
MORF: 23522
MSL1: 339287"
  },
  {
    "caption": "ShRNA-mediated suppression of CBP, TIP60, MORF, and MSL1 at mRNA level. Data represent mean ± SEM from three independent experiments, and statistical significance was determined by unpaired two-tailed t-test. *P < 0.1, **P < 0.05, ***P < 0.01.",
    "ncbi_link": "CBP: 1387
TIP60: 10524
MORF: 23522
MSL1: 339287"
  },
  {
    "caption": "Suppression of CBP, TIP60, MORF, and MSL1 sensitized cells to bendamustine. Y-axis represents relative resistance calculated from results of GFP competition assays, and statistical significance was determined by unpaired two-tailed t-test. Data represent mean ± SEM from two independent experiments. **P < 0.05, ***P < 0.01.",
    "ncbi_link": "CBP: 1387
TIP60: 10524
MORF: 23522
MSL1: 339287"
  },
  {
    "caption": "B CY exhibited enhanced activity against BCR-ABL Arf−/− murine ALL cells in vitro.",
    "ncbi_link": "ABL: 11352///11350
BCR: 110279
Arf: 12578"
  },
  {
    "caption": "C, D CY showed superior antitumor activity compared with bendamustine, SAHA, and other chemotherapeutic drugs in mice transplanted with BCR-ABL ALL cells. P-values of CY versus other drugs: NT (P = 5.02E-06) (C), SAHA (P = 4.45E-06), Bend (P = 5.18E-06), NT (P = 1.20E-05) (D), VCR (P = 1.13E-05), Dox (P = 8.08E-06), AraC (P = 7.62E-06), and CTX (P = 1.13E-05). Survival statistical analysis was done with the Mantel-Cox (log-rank) test of GraphPad Prism.",
    "ncbi_link": "ABL: 11352///11350
BCR: 110279"
  },
  {
    "caption": "E Therapeutic effects of CY (weekly dose) and targeted drugs PP242 (daily dose) and dasatinib (daily dose) in mice transplanted with BCR-ABL ALL cells. P-values of CY versus other drugs: NT (P = 3.94E-05), PP242 (P = 1.20E-05), and dasatinib (P = 0.99). Survival statistical analysis was done with the Mantel-Cox (log-rank) test of GraphPad Prism.",
    "ncbi_link": "ABL: 11352///11350
BCR: 110279"
  },
  {
    "caption": "Toxicity of CY190602 in patients harboring deletion of chromosome 17p (including p53 locus) compared to patients without del17p. Viability of samples was normalized to background apoptosis for individual patient samples. For all experiments, cell viability was determined after 72 h of drug treatment. Data represent mean ± SD.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Immunoblot analysis showed HEK293 transfected for 48 hours with expression vectors for TCHP, and FLAG-TCHP at N- and C- terminal. total lysates were immunoprecipitated with anti-FLAG antibodies, and blots were probed sequentially with anti-PCM1, anti-FLAG, and anti-ACTIN antibodies. IgG light chains are indicated with Red Ponceau staining. The input totals were analyzed by parallel immunoblotting as a control for the level of expression.",
    "ncbi_link": "FLAG: 
TCHP: 84260"
  },
  {
    "caption": "Immunoblot analysis showed HEK293 transfected for 48 hours with expression vectors for TCHP-FLAG C-terminal or constructs with deletions of the coiled-coil domain 1 (TCHP ∆1) and 2 (TCHP ∆2), as indicated in the scheme. total lysates were immunoprecipitated with anti-FLAG antibodies, and blots were probed sequentially with anti-PCM1, anti-FLAG, and anti-ACTIN antibodies. IgG light chains are indicated with Red Ponceau staining. The input totals were analyzed by parallel immunoblotting as a control for the level of expression.",
    "ncbi_link": "FLAG: 
TCHP: 84260"
  },
  {
    "caption": "Co-localization of TCHP-V5 and centriolar satellite proteins. HUVECs were transduced with TCHP-V5 lentivirus and stained for anti-PCM1, anti-CEP290, anti-CEP72 and anti-V5 antibodies. Scale bars, 25 µm and 5 µm in the inset. Right panel: the two-channel intensity correlation of pixels corresponding to regions identified with TCHP-V5 and satellite markers (n=90 cells; Pearson colocalization coefficient).",
    "ncbi_link": "V5: 
TCHP: 84260"
  },
  {
    "caption": "TCHP knock-down or control cells were stained for anti-PCM1 antibody. Panel below: quantification (n=50 cells; unpaired t-test; **p=0.004 vs control). Scale bars, 50 µm and 5 µm in the inset.",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Control or TCHP knock-down HUVECs were subjected to cycloheximide (CHX) and MG132 treatments for the indicated number of hours before immunoblotting. PCM1 levels were analysed in the insoluble fraction. Laminin has been used as a loading control. Below panel: Quantification of PCM1 degradation. (one-way ANOVA; *p=0.0180 vs control time 0).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Control or TCHP knock-down HUVECs were subjected to cycloheximide (CHX) and MG132 treatments for the indicated number of hours before immunoblotting. Condition as in (A), Western blot for anti-GABARAP and anti-ACTIN antibodies. Below panel: Quantification of GABARAP degradation. (one-way ANOVA; *p =0.0215 vs control time 0).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Control or TCHP overexpressing HUVECs were subjected to CHX treatment for the indicated number of hours prior to immunoblotting. Western blot was probed for anti-PCM1 and anti-V5 antibodies. Laminin has been used as a loading control.",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Control or TCHP overexpressing HUVECs were subjected to CHX treatment for the indicated number of hours prior to immunoblotting. Western blot was probed for anti-V5, anti-GABARAP and anti-ACTIN antibodies. Below panels: Quantification of C (one-way ANOVA; **p<0.0001 vs control time 0; ##p=0.0003 vs control CHX) and D (one-way ANOVA; **p<0.0001 vs control time 0; ##p=0.0056 vs control CHX).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Immunofluorescent staining for LC3 and p62 in TCHP knock-down and control cells. Scale bars, 25μm. Lower panel: quantification. (n=90 cells, unpaired t-test; LC3: **p<0.0001 vs control; p62: **p<0.0001 vs control).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Western blot of p62 and LC3 during under normal culture condition or starved condition (HBSS) or the presence of BafA1 (2 hours) in TCHP knock-down or control cells. Lower panels: p62 quantification. (one-way ANOVA; **p=0.0003 vs control, ##p=0.0093 vs shTCHP); LC3 quantification. (one-way ANOVA; **p=0.0008 vs control, ##p=0.0011 vs shTCHP).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "HUVECs were transduced with the tandem mCherry-EGFP-LC3 and with shRNA TCHP or control vectors. Left panels: Representative picture of mCherrry-EGFP-LC3 reporters. Scale bars, 25μm. Right panel: Quantification of the number of mCherry-only (red bars, autolysosomes) or double-positive (mCherry+/EGFP+; yellow bars, autophagosomes). (n=80 cells, one-way ANOVA; *p=0.0447 vs control; ##p=0.0007 vs shTCHP).",
    "ncbi_link": "EGFP: 
mCherry: 
LC3: 84557
TCHP: 84260"
  },
  {
    "caption": "Ratiometric flow cytometric analysis of mCherrry-EGFP-LC3 reporters as in C. (one-way ANOVA; *p=0.0247 vs control; ##p=0.0088 vs shTCHP).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Quantification of long-lived protein degradation assay in TCHP knock-down and control cells by flow cytometry (one-way ANOVA; **p=0.0018 vs control, ##p<0.0001 vs shTCHP).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "HUVECs were transduced with TCHP-V5 and control vectors. Western blot for anti-V5 and anti-p62 antibody during under normal culture condition or HBSS or BafA1 or Torin-1 treatment. Lower panel: quantification. (one-way ANOVA; **p=0.0044; #p=0.0117 vs TCHP-V5).",
    "ncbi_link": "V5: 
TCHP: 84260"
  },
  {
    "caption": "The postnuclear fraction (PNS) from TCHP knock-down and control HUVECs in the presence or absence of BafA1 was separated into (low-speed pellet) LSP and (high-speed pellet) HSP fractions and then analysed by immunoblots using anti p62, LC3 and GABARAP antibodies. The sub-fractions were treated with proteinase K (Prot. K) with or without Triton X- 100 (TX-100). Quantification of the Western blot: the p62, LC3 and GABARAP levels relative to respective GAPDH were quantified using densitometry analysis and normalized to the value of non-treated samples.",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Representative TEM images of autophagosomes in control and TCHP knock-down HUVECs in the complete medium after 3h incubation with BafA1 (Scale bars, 600nm): i, quantification of mean autophagic vesicles (AVs) and autophagosome (APs) area and ii, distribution of the cross-section areas of the analysed vesicles expressed in percentage. (n=7 cells; >100 vesicles per sample; AVs: unpaired t-test; **p<0.0001 vs control; APs: unpaired t-test **p<0.0001 vs control).",
    "ncbi_link": "TCHP: 84260"
  },
  {
    "caption": "Left panels: Representative single-channel and merged images of HUVECs expressing GFP-LC3 and immunostained for STX17. Scale bars, 25 µm and 2 µm in the inset. Right panels: Quantification of LC3/STX17 positive cells in the presence or absence of BafA1 (one-way ANOVA; **p=0.0060 vs control; #p=0.0136 vs control BafA1) and quantification LC3/STX17 positive puncta per cells (n=50 cells; one-way ANOVA; **p<0.0001 vs shTCHP BafA1).",
    "ncbi_link": "GFP: 
LC3: 84557
TCHP: 84260"
  },
  {
    "caption": "Expression of TCHP, p62, IL-1β, IL-8, and IL-6 in ECs from vessels wall from patients with CAD (n=8 patients per group, unpaired t-test; TCHP **p <0.0001; p62 **p = 0.0007; IL-1β **p <0.0001; IL-8 **p <0.0001; and IL-6 **p <0.0001 vs. Healthy subject).",
    "ncbi_link": "IL-8: 3576
IL-1β: 3553
IL-6: 3569
p62: 8878
TCHP: 84260"
  },
  {
    "caption": "Expression of IL-6, IL-8 and IL-1β (n=3 patients per group; one-way ANOVA; IL-6: *p = 0.0135 vs healthy DMSO; #p = 0.0180 vs patients DMSO; IL-8: *p = 0.0139 vs healthy DMSO; ##p = 0.0024 vs patients DMSO; IL-1β: *p = 0.0104 vs healthy DMSO; ##p = 0.0069 vs patients DMSO).",
    "ncbi_link": "IL-8: 3576
IL-1β: 3553
IL-6: 3569"
  },
  {
    "caption": "Left panels: representative images of the heart of wild-type and Tchp knock-out mice stained for CD31 (green) and p62 (magenta). Scale bars, 100µm, and 50µm for the inset. Right panels: Quantification of the percentage of cardiac area (n=4 mice per group; unpaired t-test; **p=0.083 vs wild-type) or vessels positive for p62 (n=4 mice per group; unpaired t-test; **p=0.058 vs wild-type) and vessel density (n=4 mice per group; unpaired t-test; **p=0.0097 vs wild-type).",
    "ncbi_link": "Tchp: 77832"
  },
  {
    "caption": " F qPCR analysis of Efnb2, Cdh5 and Kdr expression (normalized to Actb) in aged human endocrine glands compared to young glands. Data information: (n=4), P-values, and two-tailed unpaired t-tests for all the above panels. ns: not significant; *: P < 0.05; **: P < 0.01; ****: P < 0.0001. Human samples from donors at ages below 20 years and over 70 years were chosen for young and aged group sets, respectively. ",
    "ncbi_link": "Actb: 60
Cdh5: 1003
Efnb2: 1948
Kdr: 3791"
  },
  {
    "caption": " E Representative 3D images of pancreas from adult Vegfr2i∆EC mutant and control mice with Insulin, CD31 and Emcn immunostainings. F Combo plot (left) with quantification of CD31+ Emcnhi vessel density in Vegfr2i∆EC and control pancreatic islet. Right combo plot with insulin estimation in pancreas by ELISA assay. Nuclei: DAPI or TO-PRO-3 as indicated. Is: pancreatic islet. f.u: fluorescence unit.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": " G Representative 3D images in the upper panel show CXCR4, Ki67 and VE-Cadherin in islets from Vegfr2i∆EC mutant and control mice. 3D images (lower panel) show Vegfr2i∆EC mutant and control islets immunolabeled with Insulin and VE-Cadherin. H Combo plot (top) shows the percentage of CXCR4+ β-cells per islet in Vegfr2i∆EC mutant and control pancreatic islet. Combo plot (middle) shows the quantification of Ki67+ β-cells normalized to the number of β-cells. Combo plot (bottom) shows the percentage of Insulin+ β-cells per islet. Nuclei: DAPI or TO-PRO-3 as indicated. Is: pancreatic islet. f.u: fluorescence unit.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": " I Graph shows qPCR analysis of Pdgfa, Pdgfb, Igf1, Igf2, Cxcl12, Hgf and Kitl expression (normalized to Actb) in purified CD31+ Emcnhi ECs compared to CD31+ Emcnlo ECs. ",
    "ncbi_link": "Actb: 
Cxcl12: 20315
Hgf: 15234
Igf1: 16000
Igf2: 16002
Kitl: 17311
Pdgfa: 18590
Pdgfb: 18591"
  },
  {
    "caption": " K Bar graphs show qPCR analysis of Dll4, Emcn, Kdr, Flt4, Sele, Mmp9, Plxnd1, Robo4, Unc5b, Cdh5, Cldn5, Gja1, Gja4, Icam1, Icam2, Jam3, Ntn1, Ntn2, Ocln, Pecam1, Tjp1, Tjp2, Tjp3 and Vcam1 expression (normalized to Actb) in purified CD31+ Emcnhi ECs compared to CD31+ Emcnlo ECs from murine pancreas. ",
    "ncbi_link": "Actb: 
Cdh5: 1003
Cldn5: 12741
Dll4: 54485
Emcn: 59308
Flt4: 14257
Gja1: 14609
Gja4: 14612
Icam1: 15894
Icam2: 15896
Jam3: 83964
Kdr: 3791
Mmp9: 17395
Ntn2: 102467474
Ntn1: 18208
Ocln: 18260
Pecam1: 18613
Plxnd1: 67784
Robo4: 74144
Sele: 20339
Tjp1: 21872
Tjp2: 21873
Tjp3: 27375
Unc5b: 107449
Vcam1: 22329"
  },
  {
    "caption": " L Graph shows qPCR analysis of Gja1 expression (normalized to Actb) in purified CD31+ Emcnhi ECs from juvenile, adult and aged murine pancreas. ",
    "ncbi_link": "Actb: 
Gja1: 14609"
  },
  {
    "caption": " A Representative tile scan 3D images with α-SMA, Isolectin, FABP4 and Emcn in the pancreas from 17-weeks-old Gja1i∆EC mutant and control mice. Insets show higher magnifications of regions. B Box whiskers, and scatter plot (left) shows the quantification of CD31+ Emcnhi vessel density in Gja1i∆EC mutant and control pancreatic islets. (n=7), P-value, and two-tailed unpaired t-test. Combo plot (right) shows the quantification of P-Histone H3+ EC numbers per islet (f.u) counted on thick murine pancreatic sections. (n=5), P-value, and two-tailed unpaired t-test. C 3D images show CD31 and Emcn immunostaining in the Gja1i∆EC mutant and control pancreas. The scale bars are 50 µm. D Combined violin, scatter and sample distribution plot shows the quantification of β-cell mass (%) in pancreatic islets from Gja1i∆EC and control mice. Data represent mean ± s.d. (n=140 islets from 7 pancreas), P-value, and two-tailed unpaired t-test. E Representative 3D images with immunostaining of α-SMA, Insulin and VE-Cadherin in the pancreatic islets from Gja1i∆EC and control mice. The scale bars are 50 µm. F Combo plot (left) shows insulin measurement in lysate of pancreas by ELISA. Combo plot (right) shows the percentage of Insulin+ β-cells per islet in Gja1i∆EC mutant and control mice. (n=5), P-values, and two-tailed unpaired t-tests. Data information: The dashed lines in panel A represent the outlines of pancreas. The dashed lines in panel C, E, G, H and I represent the outlines of pancreatic islets. Two-tailed Student's t-test were performed for the statistical analysis. **: P < 0.01; ****: P < 0.0001. Nuclei: DAPI Is: pancreatic islet. f.u: fluorescence unit. The line on the right side of the combo plots represent the sample distribution. Scale bars are 200 µm for tile scan images of longitudinal thick sections across the entire glands, and 50 µm for the higher magnification insets images.",
    "ncbi_link": "Gja1: 14609"
  },
  {
    "caption": " G Representative 3D images of ESM-1 and Caveolin-1 in pancreatic islets from Gja1i∆EC and control mice. Insets (* and #) show higher magnifications with surface rendering for ESM-1 and Caveolin-1 immunostaining. Combo plot with the quantification of ESM-1+ cell numbers per islet (f.u). (n=5), P-value, and two-tailed unpaired t-test. The scale bars for the 3D images are 50 µm, and 5 µm for the higher magnifications with single-cell resolution images. The dashed lines in panel C, E, G, H and I represent the outlines of pancreatic islets. Two-tailed Student's t-test were performed for the statistical analysis. **: P < 0.01; ****: P < 0.0001. Nuclei: TO-PRO-3 as indicated. Is: pancreatic islet. f.u: fluorescence unit. ",
    "ncbi_link": "Gja1: 14609"
  },
  {
    "caption": " H 3D images with CXCR4 and Emcn immunostaining in Gja1i∆EC and control pancreas. The scale bars are 50 µm. I Representative 3D images show CXCR4, Ki67 and VE-Cadherin immunostaining in Gja1i∆EC and control pancreas. The scale bars are 50 µm. J Combo plots show the percentage of CXCR4+ β-cells per islet and Ki67+ β-cells normalized to the total number of β-cells per islet in Gja1i∆EC mutant versus the littermate control mice. (n=5), P-values, and two-tailed unpaired t-tests. K Box whiskers, and scatter plot shows the quantification of CD31+ Emcnhi vessel density in aged Gja1i∆EC mutant and control pancreatic islets. Data represent mean±s.d. (n=4), P-value, and two-tailed unpaired t-test. Combo plot (below) shows the quantification of β-cells on thick murine pancreatic sections. Data represent mean±s.d. (n=4), P-value, and two-tailed unpaired t-test. Data information: The dashed lines in panel C, E, G, H and I represent the outlines of pancreatic islets. Two-tailed Student's t-test were performed for the statistical analysis. **: P < 0.01; ****: P < 0.0001. Nuclei: TO-PRO-3",
    "ncbi_link": "Gja1: 14609"
  },
  {
    "caption": "(B) Identification of the endogenous SUMO-sites in IRF2BP1 (left panel) and IRF2BP2 (right panel). HeLa cells were transfected with HA-tagged wildtype (WT) or mutant (KR) proteins, endogenous SUMO-IPs were performed and the HA-signal was analyzed by immunoblotting. Mutation of the C-terminal SUMO-site abolished SUMOylation of IRF2BP1 and IRF2BP2 in HeLa cells.",
    "ncbi_link": "HA: 
IRF2BP1: 26145
IRF2BP2: 359948"
  },
  {
    "caption": "(E) Stable HeLa cells expressing pIRES-empty vector, IRF2BP1 WT or IRF2BP1 K579R were treated with siRNA against endogenous IRF2BP1 or non-targeting (nt) siRNA. Exogenous siRNA-resistant IRF2BP1 was expressed at low levels similar to endogenous IRF2BP1. * refers to an unspecific band.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(F) Wt and mutant IRF2BP1 localizes in the nucleus. After knockdown of endogenous IRF2BP1, stable IRF2BP1 (WT or K579R) cell lines were immunostained for IRF2BP1. Exogenous IRF2BP1 variants show a similar nuclear localization. Scale bar = 10 µm.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(G) IRF2BP1 wt and mutant associate with chromatin to a similar extent. HeLa cells were lysed in 0.075 % NP40 (Input). After centrifugation, the nuclei were incubated and vortexed with a nuclear extract (NE) buffer containing 170 mM NaCl. The eluates were collected and the procedure was repeated using a NE buffer with higher salt concentrations, first 290 mM, then 420 mM. Wildtype IRF2BP1, the SUMO-deficient K579R mutant and the SUMOylated wildtype form (*) all behave similarly.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(A) Stable IRF2BP1 cell lines (knocked-down for endogenous IRF2BP1) were used to perform a microarray experiment under serum starvation and upon treatment with EGF for 1 hour. A subset of 38 EGF-dependent genes are differentially regulated in IRF2BP1 wildtype cells compared to IRF2BP1 K579R cell lines (at least 1.5-fold). Among them are DUSP1 (arrow), ATF3, Fos and Egr2. Each microarray was performed in triplicates, the bars show log2 values of the fold changes for wt cells (black bars) and for KR cells (grey bars).",
    "ncbi_link": "ATF3: 467
DUSP1: 1843
Egr2: 1959
Fos: 2353
IRF2BP1: 26145"
  },
  {
    "caption": "(B) Chromatin IP reveals association of human IRF2BP1 with the proximal DUSP1 promoter in HeLa cells. Gene architecture of human DUSP1. The primers at -243/-67 ("-67"), -473/-224 ("-224") and -1170/-961 ("-916") relative to the TSS were used for ChIP experiments. IRF2BP1 and IRF2BP2 bind to the promoter region of DUSP1 between nucleotides -243 and -67.",
    "ncbi_link": "DUSP1: 1843"
  },
  {
    "caption": "(C) ChIP/qPCR experiments reveal preferential IRF2BP1 binding to the promoter region of DUSP1 between -243 and -67. Data show mean (bar) and individual data points from 2 biological replicates.",
    "ncbi_link": "DUSP1: 1843"
  },
  {
    "caption": "(D) IRF2BP1 wildtype and the K579R mutant both bind the DUSP1 promoter in the absence or presence of EGF. Stable cell lines expressing IRF2BP1 wildtype or K579R were knocked-down for endogenous IRF2BP1, followed by IRF2BP1 ChIP and DUSP1 qPCR of its promoter region -243 and -67. Data show means +/- SEM from 3 biological replicates.",
    "ncbi_link": "DUSP1: 1843
IRF2BP1: 26145"
  },
  {
    "caption": "(E) Q-PCR data after EGF treatment in IR2BP1 wildtype and K579R cell lines after knockdown of the endogenous IRF2BP1. Data show means +/- SEM from 3 biological replicates.",
    "ncbi_link": "IR2BP1: 26145
IRF2BP1: 26145"
  },
  {
    "caption": "(F) IRF2BP1 wildtype and V578A cell lines after knockdown of the endogenous IRF2BP1 were analysed for DUSP1 transcription after EGF treatment by q-PCR (left panel), data show means +/− SEM from 5 biological replicates (left panel), and IRF2BP1 protein levels. As expected, IRF2BP1 V578A is not SUMOylated (right panel). * refers to an unspecific band.",
    "ncbi_link": "DUSP1: 1843
IRF2BP1: 26145"
  },
  {
    "caption": "(G) Q-PCR data for immediate early genes after EGF treatment in the IR2BP1 wildtype and V578A cell lines after knockdown of the endogenous IRF2BP1. Data show means +/− SEM from 4 biological replicates.",
    "ncbi_link": "IR2BP1: 26145
IRF2BP1: 26145"
  },
  {
    "caption": "(A) Immunoblotting of HeLa lysates at indicated times after EGF treatment reveals enhanced DUSP1 and ATF3 expression upon knockdown of IRF2BP1. Uba2 and beta-actin serve as independent loading controls.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(C) Wound healing assay: HeLa cells were incubated with nt or IRF2BP1 siRNA for 2 days, grown to 90% confluency and analysed for wound closure with or without addition of 100 ng/ml EGF. Data show means of the relative wound density +/- SEM from 4 biological replicates.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(D) Proliferation assay: HeLa cells upon knockdown of IRF2BP1 and IRF2BP1 were analysed for cell density over 6 days in growth medium. One representative biological experiment is shown with means +/-SEM from 5 technical replicates.",
    "ncbi_link": "IRF2BP1: 26145"
  },
  {
    "caption": "(E) IRF2BP1, IRF2BP2, IRF2BP1+IRF2BP2 were knocked-down in HeLa cells for 72 hours and gene expression data were recorded by microarray analysis; non-targeting siRNAs were used as a control. IRF2BP1 and IRF2BP2 have distinct and overlapping functions. Experiments were done in triplicates.",
    "ncbi_link": "IRF2BP1: 26145
IRF2BP2: 359948"
  },
  {
    "caption": "(G) Validation of two candidate genes: IRF2BP1 and IRF2BP2 were knocked down for 72 hours in HeLa cells, and cell lysates were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "IRF2BP1: 26145
IRF2BP2: 359948"
  },
  {
    "caption": "(H) FACS-based analysis of EGFR surface expression: IRF2BP1 and IRF2BP2 were knocked down for 48 hours in HeLa cells, cells were serum starved for 16 hours, stained with fluorescent anti-EGFR antibodies and analyzed by flow cytometry. Shown are means of 3 independent experiments +/-SEM.",
    "ncbi_link": "IRF2BP1: 26145
IRF2BP2: 359948"
  },
  {
    "caption": "(I) Scatter plot of expression levels obtained in D. mel. S2 cells by our Luciferase assay pipeline vs mNeonGreen reporter expression in living D. mel. embryos, revealing a high correlation (Pearson coefficient 0.91) between the two datasets. Error bars represent standard deviations of 3-4 biological replicate measurements.",
    "ncbi_link": "mNeonGreen: "
  },
  {
    "caption": "(B-C) Comparison of normalized expression levels between wild-type configuration and motif knockouts for two types of core promoters (developmental: CG8157 (B); constitutive: RpL5 (C)). Upper panels: schematic depiction of the wild-type motif compositions (TTGTT motif in RpL5 is ignored due to its strong overlap with R-INR). Two-sample t-test: ns, not significant, *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001. The middle hinge represents the median. The Interquartile range the difference between the 75th and 25th percentiles. 3-4 biological replicate measurements.",
    "ncbi_link": "CG8157: 36700
RpL5: 3355124"
  },
  {
    "caption": "(A) Intracellular endogenous Aβ42 (green), Ankyrin-G (AnkG; magenta) and GFP (blue) in siBin1- , siCD2AP- and siControl-treated primary cortical neurons (neurons) expressing GFP immunolabelled at 9 DIV with anti-Aβ42 (clone 12F4) and anti-AnkG, analysed by spinning-disk confocal microscopy. The white rectangles indicate the dendrites (Dd) and axons (Ax) magnified below showing Aβ42 in axons and dendrites outlined based on AnkG (magenta) and GFP (blue), respectively. Scale bars, 10 µm.(B) Aβ42 line profiles in dendrites (Dd) of siControl (grey line), siBin1 (blue line) and siCD2AP (red line) neurons shown in (c).(C) Aβ42 line profiles in axons (Ax) of siControl (grey line), siBin1 (blue line) and siCD2AP (red line) neurons shown in (c).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "(D) Quantification of Aβ42 (12F4) intensity in cell body (CB), dendrite (Dd) and axon (Ax) (n=5, NCB=44-53, NDd=90-120, NAx=60-74; ****PCB<0.0001 siBin1 vs. siControl, ***PCB<0.001 siCD2AP vs. siControl, ****PDd<0.0001 siBin1 vs. siControl, ****PDd<0.0001 siCD2AP vs. siControl, ****PAx<0.0001 siBin1 vs. siControl, t-test, mean ± SEM).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "(E) Quantification of extracellular endogenous Aβ40, Aβ42 and of Aβ42/Aβ40 ratio by ELISA analysis of conditioned media of 9 DIV siBin1, siCD2AP or siControl neurons (n=6; *PAβ40=0.0270 siBin1 vs. siControl, *PAβ42/40=0.0378 siBin1 vs. siControl, *PAβ42/40=0.0463 siCD2AP vs. siControl, t-test, mean ± SEM).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "(F) Endogenous APP and APP-CTFs levels by western blot with anti-APP antibody (Y188) of siBin1-, siCD2AP- or siControl-treated neurons at 9 DIV.(G) Quantification of APP and APP-CTFs levels normalized to APP (n=4; *PAPP=0.0355 siBin1 vs. siControl, ***PAPPCTFs/APP<0.001 siBin1 vs. siControl, ****PAPPCTFs/APP<0.0001 siCD2AP vs. siControl, t-test, mean ± SEM).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "N2a cells treated with siBin1, siCD2AP or siControl.(B) Endocytosed APP detected after a 10 min pulse with 22C11 and APP-RFP (insets), analysed by epifluorescence microscopy. Scale bars, 10 µm.(C) The amount of endocytosed APP fluorescence at 10 min was quantified and normalized to APP-RFP fluorescence (n=3, NsiControl=56, NsiBin1=70, NsiCD2AP =42; mean ± SEM).(D) Non-degraded APP detected after 10 min pulse and 60 min chase with 22C11 and APP-RFP (insets), analysed by epifluorescence microscopy. Cells are outlined in white. Scale bars, 10 µm.(E) APP degradation was assessed by the decrease in the amount of endocytosed APP fluorescence at 60 min relative to time 0 (10 min pulse) in siControl cells normalized to APP-RFP fluorescence (n60min=3, NsiControl=68, NsiBin1=43, NsiCD2AP=64; ****PAPP60min<0.0001, t-test, mean ± SEM).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "N2a cells treated with siBin1, siCD2AP or siControl.(G) Endocytosed BACE1 detected upon 5 min pulse with M1 and BACE1-GFP (insets), analysed by epifluorescence microscopy. Scale bars, 10 µm.(H) The amount of endocytosed BACE1 per cell was quantified as percentage of siControl normalized to BACE1-GFP (n=3, NsiControl=86, NsiBin1=72, NsiCD2AP=113; mean ± SEM).(I) Recycled BACE1 detected at the plasma membrane of non-permeabilized cells with M1, upon a 10 min pulse, acid stripping and 20 min chase, and BACE1-GFP (insets), analysed by epifluorescence microscopy. Scale bars, 10 µm.(J) The amount of recycled BACE1 was quantified as in (h) (n=3, NsiControl=94, NsiBin1=58, NsiCD2AP=109; ****P<0.0001 siBin1 vs. siControl, t-test, mean ± SEM).(K) Non-recycled BACE1 detected in acid-stripped permeabilized cells pulse-chased as in (i) with M1 and BACE1-GFP (insets), analysed by epifluorescence microscopy. Scale bars, 10 µm.(L) The amount of non-recycled BACE1 was quantified as in (h) (n=3, NsiControl=61, NsiBin1=51; ****P<0.0001 siBin1 vs. siControl, t-test; n=2, NsiCD2AP=37; mean ± SEM).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "(A - D) APP endocytic trafficking followed in neurons expressing APP-RFP treated with siCD2AP or siControl using a pulse-chase assay with 22C11, analysed by epifluorescence microscopy.(A) Endocytosed APP detected with 22C11 (10 min pulse; top panels) and APP-RFP (bottom panels). Arrowheads identify axons (Ax) and dendrites (Dd) magnified on the right. Scale bars, 10 µm.(B) The amount of endocytosed APP (10 min) in cell body, dendrites and axons normalized to APP-RFP expression in the cell body quantified as percentage of siControl (n=3, NsiControl=19, NsiCD2AP=20; mean ± SEM).(C) Endocytosed APP detected with 22C11 (10 min pulse, 60 min chase; top panels) and APP-RFP (bottom panels). Arrowheads identify axons (Ax) and dendrites (Dd) magnified on the right. Scale bars, 10 µm.(D) The amount of endocytosed APP (60 min chase) was quantified as in (b) (n=3, NsiControl=23, NsiCD2AP=19; **PCB=0.001 siCD2AP vs. siControl, ***PDd=0.0004 siCD2AP vs. siControl, t-test; #P=0.0347 Dendrite vs. Cell body, ###P=0.0008 Dendrite vs. Axon, 1-way ANOVA with Tukey's multiple comparisons test; mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(E) Degradation of surface biotinylated APP (biotin APP) (time 0) chased for 20 and 60 min in neurons treated with siCD2AP, siBin1 or siControl. Biotin APP and total APP were detected with anti-APP (Y188) by western blot.(F) Quantification of biotinylated APP normalized to levels at time 0 (n=3-4, *P60min=0.0198, t-test; replicates and mean).",
    "ncbi_link": "Bin1: 30948
CD2AP: 12488"
  },
  {
    "caption": "(A - D) BACE1 endocytic trafficking followed in siBin1- and siControl-treated neurons expressing BACE1-GFP N-terminally tagged with FLAG using a pulse/chase assay with M1, an anti-FLAG antibody, analysed by epifluorescence microscopy.(A) Endocytosed BACE1 detected with M1 (15 min pulse; top panels) and BACE1-GFP (bottom panels). Arrowheads identify axons (Ax) and dendrites (Dd) magnified on the right. Scale bars, 10 µm.(B) The amount of endocytosed BACE1 per cell body, dendrite and axons was normalized to BACE1-GFP expression in the cell body and quantified as percentage of siControl (n=3, NsiControl=17, NsiBin1=19, mean ± SEM).(C) Recycled BACE1 detected with M1 (15 min pulse, acid stripping and 20 min chase; top panels) at the plasma membrane of non-permeabilized neurons and BACE1-GFP (bottom panels). Arrowheads identify axons (Ax) and dendrites (Dd) magnified on the right. Scale bars, 10 µm.(D) The amount of recycled BACE1 analysed as in (b) (n=4, NsiControl=31, NsiBin1=38, ***PCB=0.0002 and ****PAx<0.0001 siBin1 vs. siControl, t-test; ##P=0.0014 Axon vs. Dendrite, 1-way ANOVA with Tukey multiple comparisons test; mean ± SEM).",
    "ncbi_link": "Bin1: 30948"
  },
  {
    "caption": "(A) Endocytosed APP (green) detected with 22C11 (10 min pulse and 60 min chase) in EEA1-positive early endosomes (magenta) in dendrites of siCD2AP- and siControl-treated neurons expressing APP-RFP, analysed by spinning-disk confocal microscopy. Scale bar, 10 µm. The white squares indicate an EEA1-positive endosome magnified on the right. Scale bar, 1 µm.(B) Quantification of colocalisation between endocytosed APP and EEA1 in dendrites (n=3, NsiControl=26 NsiCD2AP=18; ****P<0.0001, t-test; mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(C) Non-recycled BACE1 (green) detected with M1 (15 min pulse, acid stripping and 20 min chase) in Rab5-positive early endosomes (magenta) in axons of siControl- and siBin1-treated neurons expressing Rab5-mCherry and BACE1-GFP, analysed by spinning-disk confocal microscopy. Scale bar, 10 µm. White squares indicate a Rab5-positive endosome magnified on the right. Scale bar, 1 µm.(D) Quantification of colocalisation between non-recycled BACE1 and Rab5 in axons (n=3, NsiControl=19, NsiBin1=24; ****P<0.0001, t-test; mean ± SEM).",
    "ncbi_link": "Bin1: 30948"
  },
  {
    "caption": "(E) APP (magenta) and BACE1 (green) colocalisation in dendrites of siCD2AP- and siControl-treated neurons expressing APP-RFP and BACE1-GFP upon DAPT treatment, recorded by time-lapse spinning-disk confocal microscopy for 120 sec (1 fps) (see supplementary movie 1). APP and BACE1 in dendrites at 0 sec are shown and during 120 sec in kymographs (bottom panels). Dotted white lines in kymographs highlight APP vesicles positive for BACE1. Scale bar, 10 µm.(F) Quantification of the colocalisation between APP and BACE1 in dendrites (n=3, NsiControl=18, NsiCD2AP=21; ****P<0.0001, t-test; mean ± SEM)",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(G) APP (magenta) and BACE1 (green) colocalisation in axons of siBin1- and siControl-treated neurons expressing APP-RFP and BACE1-GFP upon DAPT treatment, recorded by time-lapse spinning-disk confocal microscopy for 120 sec (1 fps) (see supplementary movie 2). APP and BACE1 in axons at 0 sec are shown and during 120 sec in kymographs (bottom panels). Dotted white lines in kymographs highlight APP vesicles positive for BACE1. Scale bar, 10 µm.(H) Quantification of the colocalisation between APP and BACE1 in axons (n=4, NsiControl =17, NsiBin1=27; ****P<0.0001, t-test; mean ± SEM).",
    "ncbi_link": "Bin1: 30948"
  },
  {
    "caption": "(A) BACE1 carriers in axons of siBin1- or siControl-treated neurons expressing BACE1-GFP, analysed by epifluorescence microscopy. Scale bar, 10 µm. White rectangles indicate a BACE1-positive carrier magnified on the right. Scale bar, 1 µm.(B) Quantification of the percentage of siBin1- or siControl-treated neurons displaying extended BACE1 carriers (as shown in (a)); (n=3, NsiControl=67 cells, NsiBin1=68 cells; *P=0.0199, t-test, mean ± SEM).(C) Quantification of circularity of individual BACE1 carriers in axons and in dendrites of siBin1- or siControl-treated neurons. The percentage of BACE1 tubules (defined by circularity < 0.5; n=2, NAx=116 and NDd=134 of siControl carriers, NAx=71 and NDd=134 of siBin1 carriers; *P=0.0105 siBin1-axons compared to siControl-axons, t-test, mean ± SEM).(D) Quantification of average size (μm2) of individual BACE1 carriers in axons and in dendrites of siBin1- or siControl-treated neurons (n=2, NAx=116 and NDd=134 siControl, NAx=71 and NDd=134 siBin1; **P=0.0019, Mann-Whitney test, mean ± SEM).",
    "ncbi_link": "Bin1: 30948"
  },
  {
    "caption": "(E and F) BACE1 (green) exit in tubular carriers from Rab5-positive early endosomes (magenta) in axons of siBin1- (f) and siControl- (e) treated neurons expressing BACE1-GFP and Rab5-mCherry using time-lapse spinning-disk confocal microscopy (4 fps) (see EV movie 3). BACE1 and Rab5 are shown in axons at 0 sec and 4.75 sec. Scale bars, 10 µm. White rectangles indicate the region used in kymographs shown on the right. Arrows and kymographs (covering 3 or 4.75 sec) of merged BACE1 and Rab5 or BACE1 alone indicate in (E) a BACE1 punctum that exits in a tubular carrier from a Rab5-positive early endosome (asterisk) and in (F) a BACE1 tubule that emanates from a Rab5-positive early endosome. Scale bars, 1 µm",
    "ncbi_link": "Bin1: 30948"
  },
  {
    "caption": "(A) APP detected with anti-APP (Y188, green) at early endosomes (anti-EEA1, magenta) in dendrites of siCD2AP- and siControl-treated neurons with or without DAPT treatment, analysed by spinning-disk confocal microscopy. Scale bar, 10 µm. White squares are magnified on the right panels. Scale bar, 1 µm.(B) Quantification of colocalisation between APP and EEA1-positive dendritic endosomes (n=3, NsiControl DMSO=15, NsiControl DAPT=14; NsiCD2AP DMSO=21, NsiCD2AP DAPT=22; ****P<0.0001 siCD2AP DMSO vs. siControl DMSO, ####P<0.0001 siCD2AP DAPT vs. siCD2AP DMSO, t-test, mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(C) APP (green) distribution within enlarged Rab5QL-GFP endosomes (magenta) in dendrites of siCD2AP- or siControl-treated neurons expressing APP-RFP and Rab5QL-GFP upon DAPT treatment, analysed by spinning-disk confocal microscopy. Scale bar, 10 µm. White squares indicate a Rab5QL-positive endosome magnified on the right. Scale bar, 1 µm.(D) Qualitative analysis of APP distribution between the lumen and the membrane of Rab5QL-endosomes (n=4, NsiControl=45 (774 endosomes), NsiCD2AP=52 (888 endosomes); *P=0.0368 siCD2AP vs. siControl, t-test, mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(E - F) APP (green) distribution within enlarged Rab5QL-GFP endosomes (magenta) in cell bodies of siCD2AP- (f) or siControl- (e) treated neurons expressing APP-RFP, upon DAPT treatment, analysed by spinning-disk confocal microscopy. APP (green) and Rab5QL (magenta) line intensity profiles along the endosome (see inset line) are shown on the right. Scale bars, 1 µm.(G) Quantification of the amount of APP fluorescence at the limiting endosomal membrane normalized to total APP fluorescence per endosome (n=3, NsiControl=32 endosomes (11 cells), NsiCD2AP=39 endosomes (15 cells); ****P<0.0001, t-test, mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(H) APP detected with anti-APP (Y188, green) at early endosomes (anti-EEA1, magenta) in dendrites of siCD2AP- and siControl-treated neurons upon DAPT treatment, analysed by super-resolution dSTORM imaging. Scale bars, 200 nm.",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "(I) Qualitative analysis of super-resolved APP distribution between the lumen and the membrane of EEA1-positive endosomes of siCD2AP- or siControl-treated neurons upon DAPT treatment (n=3, NsiControl=35, NsiCD2AP=57, **P=0.0012, Mann-Whitney test, mean ± SEM).",
    "ncbi_link": "CD2AP: 12488"
  },
  {
    "caption": "B In vitro deubiquitination of Ub chains synthesized by HOIP- and LUBEL-RBR-C. Ub chains produced by RBR-C (Human or Drosophila) with UbcH7, UbcD10 or Effete were incubated with a linear linkage-specific DUB, OTULIN (WT or catalytically dead C129A (C/A) mutant) or a Lys-linkage-specific DUB, vOTU. The DUB-treated samples were subjected to Coomassie staining or immunoblotting using anti-Ub antibody.",
    "ncbi_link": "vOTU: 31789
OTULIN: 90268"
  },
  {
    "caption": "C Thioester formation assay using Atto647-labelled Ub. Ubiquitination assay using LUBEL-RBR-C WT (left panel) or C2704A (right panel): lanes 1/2 Atto-Ub + E1, lanes 3/4 + ATP, lanes 5/6 + E2, lanes 7/8 + E3, and lanes 9/10 + Ub-His6. In the presence of N-terminally tagged Atto-Ub and C-terminally tagged Ub-His6, only Ub2 product can be synthesized and longer chain formation is restricted. Samples are run without or with DTT in odd or even numbered lanes, respectively. The gels monitor the Atto-labelled Ub.",
    "ncbi_link": "LUBEL: 33950"
  },
  {
    "caption": "E Linear Ub chain formation by full-length LUBEL transient expression in insect cells. Full-length Myc-LUBEL was transiently expressed in Drosophila Schneider 2 (S2) cells, and Myc-HOIP alone or with HA-HOIL-1L in HEK293T cells. Total cell lysates (TCL) of control and transfected samples were incubated with immobilized GST-Linear-Tandem Ub binding entity (Linear-TUBE) containing three tandem repeats of ABIN-1-UBAN. Pulldown samples were blotted with anti-linear Ub antibody, while TCL were blotted with anti-Myc antibody for exogenous LUBEL and HOIP, anti-HA antibody for HOIL-1L, and anti-Tubulin antibody for loading. Input of GST proteins was analyzed by Ponceau S staining. * : nonspecific band.",
    "ncbi_link": "LUBEL: 33950
HOIL-1L: 10616
HOIP: 55072
ABIN-1: 10318"
  },
  {
    "caption": "A Endogenous linear Ub chains enriched in total protein extracts (input, lane 1) from adult w1118 (w-) flies by GST-Linear-TUBE (lane 3). The enriched samples were further treated with recombinant DUBs, vOTU (lane 4) or OTULIN (lane 5). Ub chains were visualized by immunoblotting using anti-linear Ub antibody or anti-Ub antibody. Loading of GST proteins was analyzed by Ponceau S staining.",
    "ncbi_link": "vOTU: 31789
OTULIN: 90268"
  },
  {
    "caption": "B Endogenous linear Ub chains in total cell lysate (TCL) of S2 cells expressing human Flag-OTULIN WT or catalytically inactive C129A mutant. TCLs enriched with GST-Linear-TUBE were examined by immunoblotting using anti-linear Ub antibody. Expression of OTULIN was analyzed by anti-Flag antibody and loading of TCL was detected by anti-Tubulin antibody. Input of GST proteins was analyzed by Ponceau S staining. * : nonspecific band.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "C In vitro deubiquitination assay of dCYLD. dCYLD was incubated with all eight linkage types of Ub2 chains. dCYLD catalytically dead C284S mutant was incubated with K 63- or linear Ub2 chains. All the proteins in the reactions were resolved on Coomassie-stained SDS-PAGE gel. * : nonspecific band.",
    "ncbi_link": "dCYLD: 34380"
  },
  {
    "caption": "D Stabilization of linear Ub chains by dCYLD C284S mutant transient expression in S2 cells. Myc-tagged dCYLD WT and C284S were transfected in S2 cells and linear Ub chains were enriched with GST-Linear-TUBE and immunoblotted by anti-linear Ub or anti-Ub antibodies. Input of GST proteins was visualized by Ponceau S staining. Expression of Myc-dCYLD was examined by anti-Myc antibody, and anti-Tubulin antibody was used for the loading control of TCL.",
    "ncbi_link": "dCYLD: 34380"
  },
  {
    "caption": "E Linear Ub chains in dCYLD mutant flies. Endogenous levels of linear Ub chains in dCYLD mutant flies were compared with a control w- fly strain by performing GST-Linear-TUBE pulldown. Enriched linear Ub chains were immunoblotted with anti-linear Ub antibody. Input of GST proteins was visualized by Ponceau S staining. Tubulin was used for the loading control of the input.",
    "ncbi_link": "dCYLD: 34380"
  },
  {
    "caption": "B Linear Ub chains in w- and LUBEL mutant fly lysates. w-, CC/SS and delR2 flies were analyzed for the level of endogenous linear Ub chains by enriching the linear ubiquitin chains by GST-Linear-TUBE. Pulldown samples were immunoblotted by anti-linear Ub antibody, while GST-proteins were analyzed by Ponceau S staining. Anti-Tubulin antibody was used for the loading control of the input. * : nonspecific band.",
    "ncbi_link": "LUBEL: 33950"
  },
  {
    "caption": "C The lifespans of female w- and catalytically dead LUBEL mutant flies (two clones of CC/SS, indicated as #1 and #2, and delR2). Survival of three independent cohorts with approximately 80 flies each was monitored over time. Median survival time (days): w- = 78, CC/SS #1 = 68, CC/SS #2 = 65, and delR2 = 71. Total sample sizes are as follow; w- = 215, CC/SS #1 = 242, CC/SS #2 = 233, delR2 = 273. Log-rank (Mantel-cox) test between fly lines: w- and CC/SS #1 > 0.0001, w- and CC/SS #2 > 0.0001, w- and delR2 > 0.0001, CC/SS #1 and CC/SS #2 = 0.0007, CC/SS #1 and delR2 = not significant, CC/SS #2 and delR2 = not significant.",
    "ncbi_link": "LUBEL: 33950"
  },
  {
    "caption": "D Histological analysis of muscle in LUBEL mutant flies. Hematoxylin and eosin (H&E) (top panels) and actin immunofluorescent staining (Actin-IF) (bottom panels) of thorax muscles from young (Day 3) or aged (Day 60) w- or CC/SS female flies. Scale bars: 50 μm.",
    "ncbi_link": "LUBEL: 33950"
  },
  {
    "caption": "B Survival of catalytically dead LUBEL mutant flies upon heat shock. Young adult flies (15 males and 15 females) were incubated in a 36 °C water bath and immobilized flies were counted over the time indicated. Median survival time (hours): w- = 9.25, CC/SS #1 = 5.5, CC/SS #2 = 5, delR2 = 5.75, CC/SS #1/+ = 8.5, CC/SS #2/+ = 10, delR2/+ = 8. p-values calculated by Gehan-Breslow-Wilcoxon test between fly lines: w- and CC/SS #1, CC/SS#2, or delR2 > 0.0001, w- and CC/SS #1/+ = 0.0134, w- and CC/SS #2/+ = ns, w- and delR2/+ = 0.0002, CC/SS #1 and CC/SS #1/+ > 0.0001, CC/SS #2 and CC/SS #2/+ > 0.0001, delR2 and delR2/+ > 0.0001. Representative data are shown from six independent experiments.",
    "ncbi_link": "LUBEL: 33950"
  },
  {
    "caption": "C Survival of whole body or muscle-specific LUBEL knockdown flies upon heat shock. shRNA-based knockdown (KD) of LUBEL were driven by Tub-Gal4 or Mef2-Gal4 flies. Control fly lines (Tub-Gal4/+ and Mef2-Gal4/+) were used to compare with the KD flies. 15 males and 15 females per each line were used in this assay. Median survival time (hours): Tub-Gal4/+ = 7, Tub-Gal4>LUBEL = 3.5, Mef2-Gal4/+ = 7.5, Mef2-Gal4>LUBEL= 7. p-values calculated by Gehan-Breslow-Wilcoxon test: Tub-Gal4 <0.0001 (****), Mef2-Gal4 = 0.0029 (**). Representative data are shown from three independent experiments.",
    "ncbi_link": "Tub: 
LUBEL: 33950
Gal4: 855828
Mef2: 36032"
  },
  {
    "caption": "D Heat-induced mRNA expression of HSP70. w-, CC/SS #2 and delR2 flies were heat treated for 60 min and recovered for 1 hour, and mRNA HSP70 was quantified by qPCR. Rp49 was used as a reference and w- untreated sample was used as calibrator to calculate the expression ratio. Data are presented as meanSD (*<0.01, ***<0.001, ****<0.0001). Representative data are shown from three independent experiments.",
    "ncbi_link": "HSP70: 
Rp49: "
  },
  {
    "caption": "TRIP6 promotes YAP activity by inhibiting LATS1/2 (A) Full length (WT), the amino-terminal half (1-277), or the carboxy-terminal half (278-476) of TRIP6 were tested for binding to LATS2 by immunoprecipitation. FLAG-TRIP6 variants were co-expressed with LATS2-GFP in HEK293 cells, anti-FLAG or control (IgG) antibodies were used to isolate immune complexes. Immune complexes and lysates were probed by western blotting for LATS2-GFP and FLAG-TRIP6. Schematic diagram depicts TRIP6 domains (NES: Nuclear Export Signal; LIM: LIM domain; PDZ: PDZ domain binding motif).",
    "ncbi_link": "LATS2: 26524
TRIP6: 7205"
  },
  {
    "caption": "The regions marked in green depict TRIP6 binding sites on LATS2 (D) Lysates from HEK293A cells transfected with control or FLAG-TRIP6 plasmid were analyzed by western blotting using the indicated antibodies (quantification is shown in (F)).",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(E) Lysates from control (WT) or CRISPR generated TRIP6 null (TRIP6-KO) HEK293A cells were analyzed by western blotting using the indicated antibodies (quantification shown in (G)).",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(H) GFP-MST2 was expressed with or without FLAG-TRIP6 in HEK293 cells and the levels of MST2, MST2 activating phosphorylation (pMST2-T180), and FLAG-TRIP6 were measured by western blotting with the indicated antibodies. (Mean ± SD; n=3; n.s.≥0.05, T-test).",
    "ncbi_link": "MST2: 
TRIP6: "
  },
  {
    "caption": "(I) TRIP6 was overexpressed in HEK293A cells and the levels of TRIP6, and YAP target gene expression was analyzed using RT-qPCR. (Mean ± SD; n=3; *P≤0.05, **P≤0.01, ****P≤0.0001, T-test).",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(J) The levels of YAP target gene expression was analyzed using RT-qPCR in control (WT) and TRIP6-KO HEK293A cells. (Mean ± SD; n=3; ***P≤0.001, T-test)",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(K) Control (WT) and TRIP6-KO HEK293A cells were stained for YAP and TRIP6. Merged image shows YAP (green), TRIP6 (red), and DNA (blue). Quantification of at least 100 cells is shown (Mean ± SD; n=3; ****P≤0.0001, Fisher's test). Scale bar=20µm.",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(A) LATS2-GFP and Myc-MOB1A were overexpressed in HEK293 cells with or without co-overexpression of full length FLAG-TRIP6 and FLAG-TRIP6 1-277. Myc-MOB1A was immunoprecipitated using anti-Myc antibodies and immune complexes were assayed for Myc-MOB1A and LATS2-GFP levels. Levels of FLAG-TRIP6, FLAG-TRIP6 1-277, Myc-MOB1A, and LATS2-GFP in the lysate are also shown. The levels of LATS2-GFP in immune complexes relative to the level of Myc-MOB1A are shown in the graph (Mean ± SD; n=3; **P≤0.01, T-test)",
    "ncbi_link": "LATS2: 26524
MOB1A: 55233
TRIP6: 7205"
  },
  {
    "caption": "(A) MCF10A cells were infected with lentivirus carrying control shRNA (shEGFP), or a mix of two different shRNA against TRIP6 (shTRIP6-1 and shTRIP6-4) and were stained for TRIP6 and LATS1. Merged images show LATS1 (green), TRIP6 (red) and DNA (blue) (quantification of LATS1 localization at cell-cell junctions is shown in Figure EV3D). Scale bar=20µm.",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(B) LATS1 and LATS2 were knocked down using siLATS1 and siLATS2 SMARTPools in MCF10A cells. MCF10A control cells were treated with control siRNA (siControl) against fire fly luciferase. Cells were stained for TRIP6 and LATS1 as in (A) (quantification of TRIP6 localization at cell-cell junctions is shown in Figure EV3E). Scale bar=20µm.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524"
  },
  {
    "caption": "(G) MCF10A cells infected with lentivirus carrying control shRNA (shEGFP), or a mix of two different shRNA against TRIP6 (shTRIP6-1 and shTRIP6-4), were grown at high density on PDMS membranes and were stretched or not (only stretched cells shown) at 17% elongation for 2 hours, fixed while under tension, and were stained for TRIP6 and LATS1 as in (A). Scale bar=20µm.",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(H) Cells were treated as in (G) and YAP target gene (CTGF and Cyr61) and TRIP6 expression were analyzed using RT-qPCR. (Mean ± SD; n=3; *P≤0.05, **P≤0.01, T-test).",
    "ncbi_link": "CTGF: 1490
Cyr61: 3491"
  },
  {
    "caption": "(I) TRIP6 expression levels in (H) in control (shEGFP) and TRIP6 (shTRIP6) knockdown cells just prior to stretch were analyzed using RT-qPCR. (Mean ± SD; n=3; *P≤0.05, T-test).",
    "ncbi_link": "TRIP6: 7205"
  },
  {
    "caption": "(D) Vinculin was knocked down using two different siRNAs or control siRNA in MCF10A cells and the cell lysates were probed by western blotting for phospho-LATS1 (T1079 and S909), phospho-YAP (S127), LATS1, YAP, vinculin, and tubulin antibodies and the relative levels quantified (Mean ± SD; n=3; **P≤0.01, T-test).",
    "ncbi_link": "Vinculin: 7414"
  },
  {
    "caption": "(E) Vinculin was knocked down as described in (D) and cells were stained for YAP and vinculin. Merged image shows YAP (green), vinculin (red), and DNA (blue). Quantification of at least 100 cells is shown (Mean ± SD; n=3; ***P≤0.001, Fisher's test). Scale bar=20µm.",
    "ncbi_link": "Vinculin: 7414"
  },
  {
    "caption": "(F) Vinculin was knocked down as described in (D) and the levels of vinculin and YAP target gene expression was analyzed using RT-qPCR (Mean ± SD; n=3; ***P≤0.001, ****P≤0.0001, T-test).",
    "ncbi_link": "Vinculin: 7414
vinculin: 7414"
  },
  {
    "caption": "(G) Vinculin was knocked down in MCF10A cells as described in (D), grown at high density on PDMS membranes and cells were stretched (or not) at 17% elongation for 2 hours and the levels of vinculin and YAP target gene expression was analyzed using RT-qPCR (Mean ± SD; n=3; ***P≤0.001, ****P≤0.0001, T-test).",
    "ncbi_link": "Vinculin: 7414
vinculin: 7414"
  },
  {
    "caption": "(A) Vinculin was knocked down as described (Figure 5D) in MCF10A cells and cells were stained for LATS1 and TRIP6. Merged images show LATS1 (green), TRIP6 (red) and DNA (blue). Scale bar=20µm.",
    "ncbi_link": "Vinculin: 7414"
  },
  {
    "caption": "(B) Vinculin was knocked down as described (Figure 5D) and TRIP6 immune complexes and lysates were probed by western blotting for LATS1, TRIP6, and vinculin and the relative levels quantified (Mean ± SD; n=3; **P≤0.01, T-test).",
    "ncbi_link": "Vinculin: 7414"
  },
  {
    "caption": "(H) Vinculin was knocked down as described (Figure 5D) in MCF10A cells grown at high density on PDMS membranes. The membranes were stretched at 17% elongation for 2 hours and fixed while under tension and stained for TRIP6. Merged images show TRIP6 (red) and DNA (blue). Scale bar=20µm.",
    "ncbi_link": "Vinculin: 7414"
  },
  {
    "caption": "A, Reconstruction of the mouse brain following anterograde labeling with AAV-GFP in the ACC (I); representative coronal images showing site of injection and axonal distribution pattern in the dorsal striatum (II) and central lateral nucleus of the thalamus (III, IV). Images in aI-aIV were taken from the Allen Mouse Brain Connectivity Atlas",
    "ncbi_link": "GFP: "
  },
  {
    "caption": ", Representative in-situ hybridization images of Gal in the ILM taken from the Allen Mouse Brain Atlas representative coronal images showing the expression of Gal neurons in Gal-Cre::FLEX-YFP female mice (bottom right and left).",
    "ncbi_link": "YFP: 
Cre: 2777477
Gal: 14419"
  },
  {
    "caption": "G, Graph plots showing the fraction of c-Fos expressing Gal-positive (Galc-Fos+) and Gal-negative neurons (DAPIc-Fos+) in the CL, PCN, and CM after pup retrieval test (G, top) or object exposure (G, bottom). Data were analyzed using 2-way ANOVA and expressed as mean ± s.e.m.; n=3; *p < 0.05.",
    "ncbi_link": "Fos: 14281"
  },
  {
    "caption": "B,C, Quantification of pup retrieval latencies following ACC chemogenetic activation with hM3D (n=6) (B) or chemogenetic inhibition using hM4D (n=7) (C) compared to control groups in virgin females (n=8). Data were analyzed using 2-way ANOVA with repeated measures and are displayed as mean ± s.e.m* p< 0.05, ** p< 0.01. D, Same as (C) but for mothers (n=7)",
    "ncbi_link": "hM3D: 1131
hM4D: 1132"
  },
  {
    "caption": "G, Representative images of the CL, immunolabeled for c-Fos, following hM3D-mediated neuronal activation of the ACC. Scale bars 200 µm, 20× magnification.",
    "ncbi_link": "hM3D: 1131"
  },
  {
    "caption": "H, Spearman correlation between the hM3D-mediated activation of the ACC (as measured in (F, top)) and the CL region.",
    "ncbi_link": "hM3D: 1131"
  },
  {
    "caption": "C, Quantification of pup retrieval latencies in virgin females following CLGal+ chemogenetic activation with hM3D compared to GFP-expressing control group (n=7). Data were analyzed using 2-way ANOVA with repeated measures and are presented as mean ± s.e.m; * p < 0.05.",
    "ncbi_link": "GFP: 
hM3D: 1131
Gal: 14419"
  },
  {
    "caption": "DFL does not affect the cytokine-inducing activities of disulfide HMGB1 (ds-HMGB1). Mouse Bone Marrow Derived Macrophages were activated or not for 3 h with 3 µg/ml ds-HMGB1 (~100 nM) or 10 ng/ml LPS, in the presence of the indicated concentrations of DFL. The data points represent n=3 biological replicates, with avg ± sd, in one representative experiment (of 2 performed in different days). The levels of TNFα mRNA are not significantly different in the presence of increasing concentrations of DFL (one-way ANOVA plus post tests).",
    "ncbi_link": "TNFα: 21926"
  },
  {
    "caption": "A - L HeLa cells stably expressing FLAG-tagged UNC13D (F-UNC13D) (A and B), UNC13D stable knock-down (KD) (C, E, G, I and K) or knock out (KO) ( D, F, H, J and L) HeLa cells, and their control cells were infected with VACV (A, C and D), HSV (E and F), or SeV (K and L), or they were transfected with plasmid DNA (pDNA) (1 μg/mL) (B, G-J) for the indicated time, before immunoblotting with anti-Flag, -UNC13D, -p-TBK1, -p-IRF3, -STING, -p-P65, -p-IκB-α, -actin or -tubulin antibody.",
    "ncbi_link": "FLAG: 
pDNA: 
plasmid DNA: 
UNC13D: 201294"
  },
  {
    "caption": "UNC13D stable knock-down (KD) HeLa cells and their control cells were transfected with plasmid DNA (1 μg/mL) for the indicated time. UNC13D, IFN-β and IL6 mRNA levels were measured by qPCR (M-O).",
    "ncbi_link": "plasmid DNA: 
IFN-β: 3456
IL6: 3569
UNC13D: 201294"
  },
  {
    "caption": "UNC13D stable knock-down (KD) HeLa cells and their control cells were transfected with plasmid DNA (1 μg/mL) infected with SeV (Q) for the indicated time. The secretion of IFN-β was measured by bioassay (P and Q).",
    "ncbi_link": "plasmid DNA: 
UNC13D: 201294"
  },
  {
    "caption": "R, S UNC13D knock-out (KO) HeLa cells and their control cells were infected with GFP-HSV for 18 h or 24 h. GFP expression was visualized (left) and the green fluorescence intensity was determined by ImageJ.",
    "ncbi_link": "GFP: 
UNC13D: 201294"
  },
  {
    "caption": "B - E HeLa cells stably expressing FLAG-tagged UNC13D (F-UNC13D) (B), UNC13D stable knock-down (KD) (D) or knock-out (KO) (C and E) HeLa cells, and their control cells were stimulated with cGAMP (100 nM) for 30 min (B and C) or for the indicated time (D and E) before immunoblotting with anti-Flag, -UNC13D, -p-TBK1, -p-IRF3, -STING, -GAPDH, -actin or -tubulin antibody.",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "F- H HEK293T cells were transfected with the indicated plasmids (5 μg each) for 24 h (F and G). UNC13D knock-out (KO) and control HeLa cells were stimulated with cGAMP (100 nM) for 30 min (H). Whole cell lysates (WCL) were examined, and cell lysates were immunoprecipitated (IP) with anti-HA antibodies (F and G), IgG and anti-STING antibodies (H), followed by immunoblotting (IB) with anti-HA, -Flag antibody or the indicated antibodies.",
    "ncbi_link": "UNC13D: 201294"
  },
  {
    "caption": "UNC13D knock-out (KO) HeLa cells and HeLa cells stably expressing FLAG-tagged UNC13D (F-UNC13D) and control HeLa cells were treated with cGAMP (100 nM) for 30 min or SeV for 12 h. Confocal microscopy was used to determine the localization of endogenous STING (red), ERGIC marker ERGIC-53 (green) and nuclei (blue).",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "UNC13D knock-out (KO) HeLa cells and HeLa cells stably expressing FLAG-tagged UNC13D (F-UNC13D) and control HeLa cells were treated with cGAMP (100 nM) for 30 min or SeV for 12 h. The co-localization of STING and ERGIC was analyzed using ImageJ (J).",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "K, L UNC13D stable knock-down (KD) HeLa cells and control HeLa cells were treated with cGAMP (100 nM) for 30 min or SeV for 12 h. The aggregation of endogenous STING (red) was examined via confocal microscopy (K). Scale bar: 25 μm. The red fluorescence intensity was determined by ImageJ (L).",
    "ncbi_link": "UNC13D: 201294"
  },
  {
    "caption": "A UNC13D knock-out HeLa cells stably expressing FLAG-tagged UNC13D were stimulated with cGAMP (100 nM) or left unstimulated for the indicated time. Whole cell lysates (WCL) were examined, and cell lysates were immunoprecipitated (IP) with IgG and anti-Flag antibodies, followed by immunoblotting (IB) with the indicated antibodies.",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "UNC13D knock-out HeLa cells stably expressing FLAG-tagged UNC13D were pretreated with BFA (20 μM) or left untreated for 2 h, followed by stimulation with cGAMP (100 nM) (or left unstimulated) for 30 min. Whole cell lysates (WCL) were examined, and cell lysates were immunoprecipitated (IP) with IgG and anti-Flag antibodies, followed by immunoblotting (IB) with the indicated antibodies (E).",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "F HEK293T cells were transfected for 24h with IFN-β-luciferase reporter plasmid, pRL-TK and the indicated expression plasmids, followed by dual-luciferase reporter assays. The expression of plasmids was examined by western blotting with anti-Flag, -HA or -tubulin antibody.",
    "ncbi_link": "luciferase: 
IFN-β: 3456"
  },
  {
    "caption": "H Wild-type HeLa cells were pretreated with BFA (20 μM) or left untreated for 2 h before stimulation with plasmid DNA (1 μg/ml) for 18h or cGAMP (100 nM) for 30 min (or left unstimulated). Cell lysates were separated by native (top) or SDS (bottom) PAGE and analyzed by immunoblotting (IB) with anti-p-TBK1, -p-IRF3, -STING or -tubulin antibody.",
    "ncbi_link": "plasmid DNA: "
  },
  {
    "caption": "UNC13D stable knock-down (KD) HeLa cells and control cells were transfected with plasmid DNA (pDNA) (1 μg/mL) for the indicated time. Cell lysates were separated by native (top) or SDS (bottom) PAGE and analyzed by immunoblotting (IB) with anti-UNC13D, -p-TBK1, -p-IRF3, -STING or -tubulin antibody.",
    "ncbi_link": "pDNA: 
plasmid DNA: 
UNC13D: 201294"
  },
  {
    "caption": "UNC13D knock-out (KO) (J) HeLa cells and control cells were transfected with plasmid DNA (pDNA) (1 μg/mL) for the indicated time. Cell lysates were separated by native (top) or SDS (bottom) PAGE and analyzed by immunoblotting (IB) with anti-UNC13D, -p-TBK1, -p-IRF3, -STING or -tubulin antibody.",
    "ncbi_link": "pDNA: 
plasmid DNA: 
UNC13D: 201294"
  },
  {
    "caption": "K, L HEK293T cells were transfected with HA-tagged UNC13D, VN/VC-STING or vector for 24 h, followed by stimulation with cGAMP (100 nM) (or left unstimulated) for 30 min. Nucleus marker DAPI (blue), VN/VC-STING (green) and HA-UNC13D (red) were examined via confocal microscopy (K). The green fluorescence intensity was determined by ImageJ (L). n = 5 biological replicates.",
    "ncbi_link": "HA: 
STING: 340061
UNC13D: 201294"
  },
  {
    "caption": "D UNC13D knock-out (KO) HeLa cells, UNC13D knock-out HeLa cells stably expressing FLAG-tagged wild-type UNC13D (UNC13D RE) and FHL3 mutation (FHL3 mut), and control cells were stimulated with cGAMP (100 nM) (or left unstimulated) for 30 min. Cell lysates were separated by native (top) or SDS (bottom) PAGE and analyzed by immunoblotting (IB) with anti-UNC13D, -Flag, -p-IRF3, -STING or -tubulin antibody.",
    "ncbi_link": "FLAG: 
UNC13D: 201294"
  },
  {
    "caption": "A-C Viability counts of the indicated V. parahaemolyticus (A-B) or E. coli (C) prey strains before (0 h) and after (4 h) co-incubation with the indicated V. parahaemolyticus attackers on media containing 3% NaCl at 30°C. In A and B, media also contain 0.1% arabinose to induce expression from plasmids. In A, prey strains contain either an empty plasmid (pEmpty) or a plasmid for arabinose-inducible expression of VP1389 (pVP1389). In B and C, prey strains contain an empty plasmid that provides a selection marker, and the attackers are derivatives of a ∆hns mutant (parental). In B, the attackers contain an empty plasmid, or plasmids for the arabinose-inducible expression of VP1388 (pVP1388) or VP1390 (pVP1390). Data are shown as the mean ± SD, n = 3 technical replicates. Statistical significance between samples at the 4 h timepoint by an unpaired, two-tailed Student's t-test is denoted above. A significant difference was considered as P < 0.05. DL, assay detection limit. ∆hcp1 was used as a T6SS1- control strain. The experiment was performed at least three times with similar results; results of a representative experiment are shown.",
    "ncbi_link": "hns: 1188638
VP1388: 1188895
VP1389: 1188896
VP1390: 1188897
hcp1: 1188900"
  },
  {
    "caption": "B VP1388 and VgrG1 co-precipitate with VP1390. Immunoprecipitation using α-FLAG antibodies from V. parahaemolyticus ∆hns/∆hcp1/∆vp1390 derivatives harboring plasmids for the arabinose-inducible expression of FLAG-tagged sfGFP or VP1390. Cells were grown in MLB media supplemented with chloramphenicol to maintain the plasmids, and 0.1% arabinose. Endogenous VP1388 and VgrG1 were detected using α-VP1388 and α-VgrG1 antibodies, respectively.",
    "ncbi_link": "hns: 1188638
vp1390: 1188897
VP1390: 1188897
hcp1: 1188900"
  },
  {
    "caption": "C Expression (cells) and secretion (media) of VP1388, VP1390, and VgrG1 from the indicated V. parahaemolyticus ∆hns-derived strains harboring an empty plasmid (pEmpty) or plasmids for the arabinose-inducible expression of VP1388 (pVP1388) or VP1390 (pVP1390). Samples were grown in media containing 3% NaCl and supplemented with 0.1% arabinose at 30°C. RNA polymerase β (RNAp) was used as a non-secreted protein loading control. Arrows denote the bands at the expected size of VP1388 or VP1390, as indicated in the appropriate panels.",
    "ncbi_link": "hns: 1188638
VP1388: 1188895
VP1390: 1188897"
  },
  {
    "caption": "B VP1389 interacts with VP1390. Co-immunoprecipitation of FLAG-tagged VP1390 or BC3020 using Myc-tagged VP1389 when co-expressed in V. parahaemolyticus Δvp1389 (input). Precipitated proteins (output) were detected by immunobotting using α-Myc and α-FLAG antibodies. Source data are available online for this figure.",
    "ncbi_link": "BC3020: 
FLAG: 
Myc: 
vp1389: 1188896
VP1389: 1188896
VP1390: 1188897"
  },
  {
    "caption": "C VP1390 induces cell lysis in E. coli. Time-lapse microscopy of E. coli cells expressing periplasm-targeted sfGFP, VP1388, or VP1390 (perisfGFP, periVP1388, and periVP1390, respectively) from an arabinose-inducible vector, grown on LB agarose pads supplemented with kanamycin (to maintain the plasmid), 0.2% arabinose (to induce expression), and propidium iodide (PI; pink). Merging of the phase contrast and PI channels are shown. Scale bar = 2 µm.",
    "ncbi_link": "sfGFP: 
VP1388: 1188895
VP1390: 1188897"
  },
  {
    "caption": "Time-lapse microscopy of competition between V. parahaemolyticus ∆hns (T6SS+/VP1390+), ∆hns/∆hcp1 (T6SS-/VP1390+), or ∆hns/∆vp1390 (T6SS+/VP1390-) attackers and V. parahaemolyticus ∆vp1389 prey that express GFP. Attacker and prey were mixed (2:1 ratio) and spotted on LB agarose pads supplemented with propidium iodide (PI; pink). Merging of the phase contrast, GFP (green), and PI (pink) channels, as well as the PI channel alone are shown. Scale bar = 5 µm. The experiment was performed three times with similar results; results of a representative experiment are shown.",
    "ncbi_link": "hns: 1188638
vp1389: 1188896
vp1390: 1188897
VP1390: 1188897
hcp1: 1188900"
  },
  {
    "caption": "D) Lysate from HEK 293 cells expressing a GFP-tagged copy of either wild-type (WT) or F147/149/229/231L (F4L) TDP-43 was added to a mixture of recombinant WT or F4L TDP-43 (5.3 μM, 10% Cy3-labeled protein) and A(GU)6 (22.8 μM), A(CA)18 (7.6 μM), A(GU)18 (7.6 μM), or no RNA control at 250 mM NaCl. Droplets were imaged by brightfield and fluorescence microscopy. Representative images for 3 biological replicates using 2 protein preparations. Scale bars, 10 μm. E) LLPS measured by turbidity in the same experimental conditions as panel D. Mean and SD of 4 biological replicates using 2 recombinant protein preparations. Analyzed by one-way ANOVA (F(7,24)=69.30, P<0.0001). Sidak's multiple comparisons test was used to compare selected groups. *P<0.05, ****P<0.0001. ",
    "ncbi_link": "GFP: 
TDP-43: "
  },
  {
    "caption": "B. Quantification of the MCAK/Uba2  signal ratio normalised to each non-targeting control of 4 independent experiments. Error bars indicate standard deviation, asterisks the p-value of a two-tailed unpaired Student's t-test comparing each Fbxw5-directed siRNA sample with the according non-targeting control (*P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "Fbxw5: 54461"
  },
  {
    "caption": "C. RPE-1  cells were transfected with the indicated siRNAs (72 hours total time), split on coverslips 24 hours later and serum-starved for the last 24 hours. Cells were fixed in methanol  and analysed via  immunofluorescence  using the indicated antibodies together with Hoechst staining. Left: Maximum intensity projections (same for all following microscopy images) of representative images. Arrows indicate ODF2  signal. Scale bar = 5 µm. Note: Middle panel shows an example image of siFw5-3. Right: Quantification of  MCAK signals  co-localising with ODF2. Long black line shows mean intensity and error bars indicate standard error of the mean of 3 independent experiments covering in total more than 280 cells. Asterisks indicate p-value of a Mann Whitney test comparing each sample set with the non-targeting control (**P < 0.01, ***P < 0.001).",
    "ncbi_link": "Fw5: 54461"
  },
  {
    "caption": "A. Fluorescence-based pulse-chase experiment using a monoclonal RPE-1 cell line expressing mNG-MCAK under a doxycycline-inducible promoter. Cells were transfected with the indicated siRNAs (siFw5-1&3 together) and split 24 hours later on Ibidi 8 Well Glass Bottom µ-slides while simultaneously inducing mNG-MCAK expression with 6 ng/ml doxycycline (pulse). 24 hours later, doxycycline was washed out and cells were released into serum-free medium. Cells that have just finished or were about to finish mitosis (distinguishable for example by the midbody signal of mNG-MCAK (arrow heads)) were selected and imaged over 24 hours, taking an image every 20 min (chase). Left: representative images of selected time points. Scale bar = 10 µm. Arrows indicate centrosomal mNG-MCAK signals, arrowheads  mNG-MCAK  signals at the midbody. Right: Quantification of centrosomal mNG-MCAK  signals. Error bars show standard error of the mean of 3 independent experiments with 25 cells in total. P-value of a two-tailed unpaired Students t-test comparing signal intensity of Fbxw5  knockdown over non-targeting control was mostly below 0.01 for time points 0 to 8 hours and below 0.05 for  time points 9h to 20h. Dark and light blue lines indicate the time points at which  mNG-MCAK  signals are reduced by 50% compared to time point  0 for siNT and siFbxw5  samples, respectively.",
    "ncbi_link": "Fbxw5: 54461
Fw5: 54461"
  },
  {
    "caption": "C. RPE-1 cells were treated with the indicated siRNA for 48 hours followed by serum-starvation for another 24 hours. Cells were then fixed in methanol and subjected to  IF  using the indicated antibodies together with  Hoechst staining. Left: Representative images. Note: Left panel shows an example image of siFw5-1. Scale bar = 10 µm. Right: Quantification of ciliated cells. Error bars show standard deviation of 4 independent experiments covering more than 200 cells and asterisks indicate p-value of a two-tailed unpaired Student's t-test (*P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "Fw5: 54461"
  },
  {
    "caption": "(e,f) ELISA for IL-1β (e) and IL-18 (f) in supernatants. Resting or LPS-primed BMMs generated from wild-type (WT), Nlrp3−/−, Pycard−/− or Nlrc4−/− mice were stimulated with PA-BSA.",
    "ncbi_link": "Nlrc4: 268973
Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(g) IL-1β ELISA of supernatants from LPS-primed BMMs stimulated with PA-BSA in the absence or presence of the pan-caspase inhibitor zVAD or caspase-1 inhibitor zYVAD.",
    "ncbi_link": "caspase-1: 12362"
  },
  {
    "caption": "(h) ELISA for IL-1β in supernatants. Resting or LPS-primed BMMs generated from WT or Casp1-/- mice were stimulated with PA-BSA, BSA control, ATP or nigericin.",
    "ncbi_link": "Casp1: 12362"
  },
  {
    "caption": "(i) ELISA for TNF in supernatants. Resting or LPS-primed BMMs generated from WT, Nlrp3-/-, Pycard-/- or Casp1-/- mice were stimulated with PA-BSA as indicated. Values are expressed as mean ± s.d., and the results are representative of three independent experiments.",
    "ncbi_link": "Casp1: 12362
Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "Immunoblotting for procaspase-1 and activated caspase-1 (p10), pro-IL-1β and cleaved IL-1β (p17) in supernatants (Sup) and cell lysates (Lys) from resting or LPS-primed BMMs generated from WT, Nlrp3−/−, Pycard−/− (a) or Nlrc4−/− (b) mice stimulated with PA-BSA (0.2 or 0.5 mM) as indicated at top. Data are representative of two independent experiments.",
    "ncbi_link": "Nlrc4: 268973
Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(f) Transfection of BMMs with empty vector (EV) or constitutively active (CA) AMPK-α1 subunit. N, non-transfected. Efficiency was determined 16 h later by flow cytometric analysis of GFP expression in macrophages cotransfected with CA AMPK-α1 and pmaxGFP. Values are percentages of GFP-positive cells in the ranges indicated by the bars. (g) ELISA for IL-1β in supernatants of cells transfected as in f and stimulated with PA-BSA (0.5 mM) for 24 h. In each of a, b and f, one of two independent experiments is shown. In each of c-e and g, the results are representative of three independent experiments. Values are expressed as mean ± s.d. *P 0.05 versus controls.",
    "ncbi_link": "AMPK-α1: 105787"
  },
  {
    "caption": "(d-f) Akt Ser473 phosphorylation measured by flow cytometry (d,e) or immunoblotting (f). FL83B cells (d,e) or WT primary hepatocytes (f) were pretreated with conditioned medium (CM) generated from WT, Pycard−/− (d), Nlrp3−/− or Casp1−/− (e) macrophages for 24 h, then stimulated with insulin. Control medium was obtained from wild-type BMM cultures without stimulation.",
    "ncbi_link": "Pycard: 66824"
  },
  {
    "caption": "(d-f) Akt Ser473 phosphorylation measured by flow cytometry (d,e) or immunoblotting (f). FL83B cells (d,e) or WT primary hepatocytes (f) were pretreated with conditioned medium (CM) generated from WT, Pycard−/− (d), Nlrp3−/− or Casp1−/− (e) macrophages for 24 h, then stimulated with insulin. Control medium was obtained from wild-type BMM cultures without stimulation",
    "ncbi_link": "Casp1: 12362
Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(g) Akt serine 473 phosphorylation measured by flow cytometry. FL83B cells were pretreated with WT or Pycard−/− CM in the absence or presence of the IL-1 receptor antagonist anakinra (1 μg/ml) for 24 h, then stimulated with insulin.",
    "ncbi_link": "Pycard: 66824"
  },
  {
    "caption": "(b) ITT in WT mice on regular diet (RD) or HFD for 12 weeks, or Il1b-/- mice on HFD for 12 weeks.",
    "ncbi_link": "Il1b: 16176"
  },
  {
    "caption": "(c,d) ITT (c) and serum IL-1β (d, left) and TNF (d, right) determined by ELISA, 2 h after IL-1β injection. Recombinant mouse IL-1β was administered to WT and Tnfa−/− mice (n = 5 for each group). One of two independent experiments is shown (mean ± s.d.). *P 0.05 versus controls.",
    "ncbi_link": "Tnfa: 21926"
  },
  {
    "caption": "(a) Blood glucose and insulin levels measured in WT (n = 6), Nlrp3−/− (n = 5) or Pycard−/− (n = 6) mice under fasting or refed conditions after 12 weeks of HFD.",
    "ncbi_link": "Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(b-e) Glucose tolerance test (GTT) (b,d) and insulin tolerance test (ITT) (c,e) performed for WT, Nlrp3−/− (b,c) and Pycard−/− (d,e) mice on HFD for 12 weeks.",
    "ncbi_link": "Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(g,h) Insulin-stimulated phosphorylation of IRβ, IRS1 and Akt (Ser473) in liver tissues of individual WT and Pycard−/− mice (g), and p-Akt (Ser473) in liver, white adipose (WAT) and muscle tissues of individual WT and Nlrp3−/− mice (h) on HFD for 12 weeks, after insulin (2 IU/kg) infusion. Graphs at right of blots show the quantitation of each molecule. pY, phosphotyrosine.",
    "ncbi_link": "Nlrp3: 216799
Pycard: 66824"
  },
  {
    "caption": "(i,j) Expression of Tnfa and Mcp1 mRNA relative to Actb in liver tissues of Nlrp3−/− mice (i) and Pycard−/− mice (j) on regular diet (RD) or HFD for 12 weeks. One of two independent experiments is shown (mean ± s.d.). *P 0.05 versus controls.",
    "ncbi_link": "Actb: 
Mcp1: 20296
Nlrp3: 216799
Pycard: 66824
Tnfa: 21926"
  },
  {
    "caption": "(E-G) Effect of EPI  on CIII-deficient (BCS1L) cells stable-expressing  ATPIF1WT or  ATPIF1H49K. (E) CV ATP  hydrolytic capacity measured by the acidification rate  and normalized maximal respiration. Maximal respiration was determined using the OCR  channel (Max OCR  on SR). Effect of EPI  is shown as % of control cells, untreated with EPI. Cells were treated for 24hrs with 50nM EPI  (n≥4). (F) mtATP content measured as fluorescence intensity per mitochondria  area and shown as % of control untreated (n=5). Mitochondrial  area was quantified using MTG staining. Cells were treated for 30min. (G) Total cellular ATP  content shown as % of untreated cells. Cells were treated for 24hrs (n≥4). In all cases, data represent average ± SEM. For each biological replicate, technical replicates were averaged. Two-way ANOVA followed by Šídák's multiple comparisons test shows statistical differences depicted by p-value.",
    "ncbi_link": "ATPIF1: 11983
BCS1L: 617"
  },
  {
    "caption": "B Venn diagrams showing overlap between genes up-regulated (1.5 fold) in abo1Δ mutants with genes up-regulated under the indicated condition, along with the significance of the overlaps (based on hypergeometric distribution).",
    "ncbi_link": "abo1: 2543084"
  },
  {
    "caption": "B Nucleosome position frequency values for the coding regions of 4013 S. pombe genes were k-means clustered (k = 9) using the abo1Δ data from biorep 1 (low MNase) and displayed with positive values coloured yellow and other values coloured blue (left-hand panel). The cluster order was then used to display the equivalent wild type frequency values in the right-hand panel.",
    "ncbi_link": "abo1: 2543084"
  },
  {
    "caption": "C Level of histone gene mRNAs was determined by qRT-PCR. Data are the mean of four independent biological repeats and error bars are ±SEM. Two-tailed unpaired t-tests showed no significant differences (P > 0.05) between wild type and abo1Δ cells.",
    "ncbi_link": "abo1: 2543084"
  },
  {
    "caption": "C RNA purified from wild type, abo1Δ and spt16-18 cells was analysed by northern blotting using a probe to the 3′ end of spbc19c7.11 (top panel). RNA (5 µg) used for northern blotting was analysed on an ethidium bromide stained 1% TAE agarose gel (bottom panel). Data are representative of two independent biological repeats.",
    "ncbi_link": "abo1: 2543084
spbc19c7.11: 2540750
spt16: 2541355"
  },
  {
    "caption": "D RNA purified from wild type, and abo1Δ cells was analysed by strand specific RT-PCR. RNA from hip1Δ cells was analysed as a control. One primer, complementary to either the forward or reverse transcripts, was included during the reverse transcription step the second primer was then added during PCR amplification. Control reactions omitting the reverse transcription step (-RT) were included to demonstrate the absence of contaminating genomic DNA. Data are representative of two independent biological repeats.",
    "ncbi_link": "hip1: 2540219
abo1: 2543084"
  },
  {
    "caption": "F ChIP analysis of histone H3 levels at act1+ was determined by qPCR. Data are the mean of three independent biological repeats and error bars represent ±SEM. P-value was calculated using a two-tailed unpaired t-test.",
    "ncbi_link": "act1: 2540051"
  },
  {
    "caption": "A The position of ura4+ reporter alleles in centromere 1 is shown in the top panel. Strains containing the imr::ura4+ allele were grown to log phase in YE5S medium, subjected to 5-fold serial dilutions and spotted onto YE5S agar or YE5S agar supplemented with 5-FOA (1 mg/ml). Data are representative of three independent biological repeats.",
    "ncbi_link": "ura4: 2538768"
  },
  {
    "caption": "B Strains carrying the otr::ura4+ were analysed as described for A.",
    "ncbi_link": "ura4: 2538768"
  },
  {
    "caption": "D RNA was purified from the indicated strains and subjected to qRT-PCR for the subtelomeric gene, tlh1+. Data is the mean of three biological repeats and error bars indicate ± SEM. P-value was calculated using a two-tailed unpaired Student's t-test.",
    "ncbi_link": "tlh1: 2541932"
  },
  {
    "caption": "E The position of insertion of ade6+ reporter allele in the silent mat locus is shown in the top panel. Log phase cells containing the mat3-M::ade6+ allele were subjected to five-fold serial dilution and spotted onto YE5S agar plates lacking adenine (Low Ade) were incubated for 4 days at 30°C. Data are representative of at least three independent biological repeats. Note, microarray analysis indicates that deletion of abo1+ does not influence the expression of ade6+ (or ura4+) when these genes are present at their normal genomic loci.",
    "ncbi_link": "mat3: 
ade6: 2538734
abo1: 2543084
ura4: 2538768"
  },
  {
    "caption": "A ChIP analysis was performed on wild type (untagged) and abo1-GFP cells and the resulting DNA analysed by qPCR for centromeric (dh, dg and imr) repeat sequences. Data are the mean of four independent biological repeats and error bars represent ±SEM. P-values calculated using a two-tailed unpaired t-test indicates that all loci are significantly enriched (P < 0.05) relative the untagged control.",
    "ncbi_link": "abo1: 2543084"
  },
  {
    "caption": "B The indicated strains expressing GFP-Swi6 were subjected to ChIP analysis. The level of centromeric (dg) repeat sequences relative to the euchromatic control locus, adh1+ was determined by qPCR and scaled to a clr4Δ (- H3 K9me control) mutant. Data are the mean of two independent ChIP experiments and error bars represent the range of the data.",
    "ncbi_link": "adh1: 2538902
clr4: 2540825"
  },
  {
    "caption": "D. ChIP analysis of Abo1-GFP at centromeric (dh and imr) repeat sequences regions in wild type and pob3Δ cells. Data are the mean of three independent experiments and error bars represent ±SEM. P-values, calculated using a two-tailed unpaired t-test, indicated no significant difference (P > 0.05) for wild type and pob3Δ cells.",
    "ncbi_link": "pob3: 2541088"
  },
  {
    "caption": "F ChIP analysis of Abo1-GFP over the dh and imr regions in wild type and swi6Δ cells. Data are the mean of three independent experiments and error bars represent ±SEM. P-values, calculated using a two-tailed unpaired t-test, indicated no significant differences (P > 0.05) for wild type and swi6Δ cells.",
    "ncbi_link": "swi6: 2541633"
  },
  {
    "caption": "A RNA was extracted from mid log phase cells and Tf2 mRNA levels were determined by qRT-PCR, normalised to act1+ mRNA and scaled relative to the wild type level. Data are the mean of three independent biological repeats and error bars represent ±SEM.",
    "ncbi_link": "Tf2: 
act1: 2540051"
  },
  {
    "caption": "B Mid log phase cells with the indicated integrated lacZ reporter were subjected to quantitative β-galactosidase assays. Data are the mean of three independent biological repeats and error bars represent ±SEM.C As for B",
    "ncbi_link": "lacZ: "
  },
  {
    "caption": "D ChIP DNA samples from wild type (untagged) and abo1-GFP cells were analysed by qPCR for Tf2 LTR. Data are the mean of four independent biological repeats and error bars represent ±SEM.",
    "ncbi_link": "Tf2: 
abo1: 2543084"
  },
  {
    "caption": "E Normalised cumulative nucleosome (150 ± 30 bp) position frequency profiles for Tf2 LTR retrotransposons aligned at the ATG plotted from low MNase (biorep1) and high MNase (biorep 2) datasets.P-values were calculated using a two-tailed unpaired t-test.",
    "ncbi_link": "Tf2: "
  },
  {
    "caption": "Subcellular localization of dLap1mGFP and dTormGFP-E177Q in the wild-type (w-) or dLap1+/∆11 fat body of 3rd instar fly larvae, when expressed as UAS transgenes. ",
    "ncbi_link": "dLap1: 36670"
  },
  {
    "caption": "GFP, Phalloidin and LipidTOX detect the expression of dTormGFP chimeras (green), cell boundaries (red), and LD (red), respectively, in dTorKO fat body cells.",
    "ncbi_link": "mGFP: 
dTor: 31399"
  },
  {
    "caption": "Bars show the fraction (mean ± SEM) of membrane GL and GPL lipids with each fatty acyl chain characteristic. n = 3 MS analyses of 4DO fat body samples for each genotype. MUFA, mono-unsaturated; PUFA, poly-unsaturated. ‡ indicate a significant difference between w- and dTorKO expressing Luciferase RNAi, * indicate a significant difference compared to dTorKO expressing Luciferase RNAi. Two-way ANOVA, Dunnett's multiple comparison test. ‡ p < 0.05 and * p < 0.05.",
    "ncbi_link": "Luciferase: 
dTor: 31399"
  },
  {
    "caption": "Control and dTorKO 5DO fat body cells expressing UAS GFP fusion proteins with the Cg-Gal4 driver, and labeled with anti-Calnexin (red) and a neutral lipid dye (LipidTOX, magenta). Note that dTorKO cells are smaller. White arrowhead indicates NE enrichment of LipinmGFP.",
    "ncbi_link": "Gal4: 
GFP: 
dTor: 31399"
  },
  {
    "caption": "Lipin1mGFP localization in HEK293T cells transfected with a plasmid that co-expresses CTDNEP1myc-WT or -CD (red) and NEP1R1V5 (magenta). (G') Upper: enlargement of panel G, white arrow highlights NE enrichment. Lower: plot showing the intensity of Lipin1mGFP signal (mean ± SD, n = 5 cells) along a 3 µm profile that transects the NE at 0 µm.",
    "ncbi_link": "myc: 
CTDNEP1: 23399"
  },
  {
    "caption": "Control (w-) and dTorKO fat body nuclei labeled with anti-LaminDm0, Megator/Tpr, mAb414, or expressing UAS Nup107GFP or UAS Nup358GFP with the Cg-Gal4 driver.",
    "ncbi_link": "Gal4: 
dTor: 31399"
  },
  {
    "caption": "mAb414 labeling of 5DO dTorKO fat body cells expressing the dTor cDNA, Luciferase RNAi, or RNAi against Nep1r1, Ctdnep1, or Lipin. Nuc, nucleus. The percentage of fat body cells with NE-localized mAb414. ** and **** indicate that Lipin, Ctdnep1, and Nep1r1 RNAi significantly increased the number of dTorKO cells with NE-specific mAb414 labeling compared to the Luciferase RNAi (Luc). Chi-square test followed by individual post hoc Chi-square tests. ** p < 0.01 and **** p < 0.0001. NE ultrastructure in 5DO dTorKO cells. Red arrows, nuclear pores; yellow arrows, abnormal INM herniations. Nuc, nucleus; Cyto, cytosol.",
    "ncbi_link": "Luciferase: 
Luc: 
Nep1r1: 3355167
Ctdnep1: 33107
Lipin: 35790
dTor: 31399"
  },
  {
    "caption": "The percentage that Lipin, Ctdnep1, and Nep1r1 RNAi normalize the abundance of membrane GL and GPL classes in the dTorKO fat body. 0% "normal" reflects lipid abundance in dTorKO expressing Luciferase RNAi, while 100% "normal" reflects lipid abundance in w- expressing Luciferase RNAi. Percentage normalization was separately calculated for PI, PA, DAG, PC, PE and PS (for dTorKO expressing Lipin, Ctdnep1, and Nep1r1 RNAi). Points show the mean of all lipid class normalization per sample, bars show mean ± SEM for the group.",
    "ncbi_link": "Luciferase: 
Nep1r1: 3355167
Ctdnep1: 33107
Lipin: 35790
dTor: 31399"
  },
  {
    "caption": "NE ultrastructure of 5DO fat body cells overexpressing UAS transgenes, or from dLap1-/- animals. Yellow dotted lines highlight NE regions with subtly abnormal membrane architecture. Red arrows indicate nuclear pores. R1, region 1; R2, region2; Nuc, nucleus; Cyto, cytosol",
    "ncbi_link": "dLap1: 36670"
  },
  {
    "caption": "Data from FIB-SEM imaging of fat body nuclei expressing Sec61b (control), or CTDNEP1mGFP. (J - L) 3D reconstructions, (M) distance between the INM and ONM at NPC in wild-type cells versus CTDNEP1mGFP-induced structures. Kolmogorov-Smirnov non-parametric T-Test. **** p < 0.0001",
    "ncbi_link": "mGFP: 
CTDNEP1: 23399
Sec61b: 66212"
  },
  {
    "caption": "mAb414 localization in 5DO fat body cells expressing the indicated UAS transgenes or from a dLap1-/- animal. *** and **** indicate significant difference compared to control mGFPSec61b expressing cells. Chi-square test followed by individual post hoc Chi-square tests. *** p < 0.001 and **** p < 0.0001.",
    "ncbi_link": "mGFP: 
dLap1: 36670
Sec61b: 66212"
  },
  {
    "caption": "NE ultrastructure of 5DO fat body cells from a (I) control animal, (J) homozygous Nup35BG01311 and (K) homozygous Nup35MB02683 animals. Nuc, nucleus; Cyto, cytosol.",
    "ncbi_link": "Nup35: 32851"
  },
  {
    "caption": "D. In vitro competition assay of the 3 MCC cell lines MKL-2, PeTa, and WaGa transduced with either shLSD1.1, shLSD1.2, shRenilla (negative control), or shRPS15 (positive control). Individual graphs are displayed in Fig EV1E.",
    "ncbi_link": "Renilla: 
LSD1: 23028
RPS15: 6209"
  },
  {
    "caption": "F. Violin plot depicting the LSD1 dependency score in MCC compared to cancer types from 23 tissues, ordered according to mean dependency score. Red horizontal line depicts the median. Data obtained from DepMap RNAi screen. Blood, hematopoietic and lymphoid tissue; U. aerodigestive, upper aerodigestive tract; A. ganglia, autonomic ganglia; CNS, central nervous system.",
    "ncbi_link": "LSD1: 23028"
  },
  {
    "caption": "E. Violin plot depicting the HMG20B dependency in MCC compared to cancer types from 23 tissues, ordered according to mean. Red horizontal line depicts the median. Data obtained from DepMap RNAi screen. Blood, hematopoietic and lymphoid tissue; U. aerodigestive, upper aerodigestive tract; A. ganglia, autonomic ganglia; CNS, central nervous system.",
    "ncbi_link": "HMG20B: 10362"
  },
  {
    "caption": "K. Bar graph of HMG20B rescue experiment in PeTa cells transduced with either a shRNA targeting HMG20B (shHMG20B) or negative control (shRenilla) and with an overexpression construct expressing either of the HMG20B mutant that cannot be targeted by the shRNA. Cell survival is depicted at day 8 after transduction and normalized to shRenilla. EV, empty vector control, WT, wild-type; ΔALPHA, alpha-helices deletion; ΔCC, coiled-coil domain deletion; ΔHMG, HMG box deletion.",
    "ncbi_link": "Renilla: 
HMG20B: 10362"
  },
  {
    "caption": "B. RT-qPCR quantification of neuronal genes at the different time points and conditions depicted in Fig 7A. Data are relative to the housekeeping gene HPRT1 and normalized to the respective DMSO control. n = 4 technical replicates. Bar graphs represent mean ± SD.",
    "ncbi_link": "HPRT1: "
  },
  {
    "caption": "(F) IRE1+/+ and IRE1-/- BMDMs were treated with PA (500 µM) for 6 hours and protein lysates were analyzed by western blotting using specific antibodies against pIRE1S742, IRE1, p70S6KT389, p70S6K, pS6S235/236, S6, p4E-BP1S65, 4E-BP1 and β-actin. Western blot quantifications are shown next to the figure (n=3 biological replicates, a representative blot is shown).",
    "ncbi_link": "IRE1: 78943"
  },
  {
    "caption": "IRE1-/- and IRE1+/+ BMDMs were treated with PA (500 µM) or vehicle for 6 hours prior to RNA isolation for miRNA analysis using a micro-array platform. (B) RNA lysates from the same experiment were analyzed by qRT-PCR for miR-2137 expression.",
    "ncbi_link": "IRE1: 78943
miR-2137: 100316779"
  },
  {
    "caption": "IRE1-/- and IRE1+/+ BMDMs were treated with PA (500 µM) or vehicle for 6 hours prior to RNA isolation for miRNA analysis using a micro-array platform. (C) Protein lysates were analyzed by western blotting using specific antibodies for pIRE1S742, IRE1 and β-actin (n=3 biological replicates).",
    "ncbi_link": "IRE1: 78943"
  },
  {
    "caption": "IRE1-/- and IRE1+/+ BMDMs were treated with PA (500 µM) or vehicle for 6 hours prior to RNA isolation for miRNA analysis using a micro-array platform. (D) RNA lysates were analyzed by qRT-PCR for sXBP1 expression (n=3 biological replicates).",
    "ncbi_link": "IRE1: 78943
XBP1: 22433"
  },
  {
    "caption": "IRE1-/- and IRE1+/+ BMDMs were treated with PA (500 µM) or vehicle for 6 hours prior to RNA isolation for miRNA analysis using a micro-array platform. (E-F) RNA lysates from the same experiment were analyzed by qRT-PCR for (E) BLOC1S1 and (F) SCARA3 expression (n=3 biological replicates).",
    "ncbi_link": "BLOC1S1: 14533
IRE1: 78943
SCARA3: 219151"
  },
  {
    "caption": "(A-B) BMDMs were treated with PA, steric acid (SA), palmitoleic acid (PAO) or oleic acid (OA) (500 µM) for 16 hours. RNA lysates were analyzed by qRT-PCR for the expression of (A) miR-2137 and (B) sXBP1 (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779
XBP1: 22433"
  },
  {
    "caption": "(C, D) (C) C57BL/6 (WT) and (D) Apoe-/- mice were fed with chow or WD for 16 weeks followed by peritoneal macrophage isolation. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (WT; n=4-4 mice per group, Apoe-/-; n=5-5 mice per group).",
    "ncbi_link": "Apoe: 11816
miR-2137: 100316779"
  },
  {
    "caption": "(E-F) Apoe-/- mice were fed with chow or WD for 12 weeks and injected with 4µ8c (10 mg/kg/day) or vehicle (DMSO) in the final 6 weeks of the diet (n=5-7 mice per group): (E) RNA lysates from bone marrow were analyzed by qRT-PCR for miR-2137 expression (n=5-7 mice per group). (F) Total RNA isolated from the aortic root plaques was analyzed by qRT-PCR for miR-2137 expression (n=5-7 mice per group).",
    "ncbi_link": "Apoe: 11816
miR-2137: 100316779"
  },
  {
    "caption": "(A) BMDMs were transfected with scrambled (Scr) or IRE1-specific siRNA (40 nM) and treated with palmitate (PA, 500 µM) or vehicle for 6 and 9 hours (hr). RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates).",
    "ncbi_link": "IRE1: 78943
miR-2137: 100316779"
  },
  {
    "caption": "(B) BMDMs were treated with PA (500 µM) and 4µ8c (100 µM) or vehicle for 9 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates). (C) BMDM cells were treated with tunicamycin (Tun; 5 µg/ml) and 4µ8c (100 µM) or vehicle (DMSO) for 9 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates). ",
    "ncbi_link": "miR-2137: 100316779"
  },
  {
    "caption": "(D) IRE1-/- MEFs were transfected with vector (control), WT-IRE1 or K907A-IRE1 (RNase dead mutant) plasmids for 24 hours, followed by PA (500 µM) treatment for 9 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates).",
    "ncbi_link": "IRE1: 78943
miR-2137: 100316779"
  },
  {
    "caption": "(E) BMDMs were transfected with scrambled or XBP-1 specific siRNA (70 nM) for 24 hours, followed by treatment with PA (500 µM) for 16 hours. RNA lysates were analyzed by qRT-PCR for miR-2137 expression (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779
XBP-1: 22433"
  },
  {
    "caption": "(F) XBP1-/- MEFs were transfected with empty vector or sXBP1 plasmid for 24 hours, followed by PA (500 µM) treatment for 9 hours. RNA lysates were analyzed for miR-2137 expression by qRT-PCR (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779
XBP1: 22433"
  },
  {
    "caption": "(G) IRE1 cleavage assay performed using synthetic pre-miR-2137 (50 nM) as substrate with active, recombinant IRE1 (100 ng) at 37℃ for 2 hours, followed by sample separation in Urea-PAGE and detection with SYBR gold staining. M indicates micro RNA marker.",
    "ncbi_link": "miR-2137: 100316779"
  },
  {
    "caption": "(H-I) BMDMs isolated from WT (C57BL6) and DICER-/- mice were treated with PA (500 µM) for 12 hours. RNA lysates were analyzed by qRT-PCR for (H) miR-2137 and (I) sXBP1 expression (n=3 biological replicates).",
    "ncbi_link": "DICER: 192119
miR-2137: 100316779
XBP1: 22433"
  },
  {
    "caption": "(B) HEK293 cells were co-transfected with an INPPL1 3` UTR-luciferase plasmid and scrambled miRNA mimic (40 nM), miR-2137 mimic (40 nM) or miR-205 mimic (40 nM) for 24 hours. Protein lysates were analyzed for luciferase activity and normalized to secreted embryonic alkaline phosphatase (SEAP) reporter activity (n=3 biological replicates).",
    "ncbi_link": "alkaline phosphatase: 
luciferase: 
INPPL1: 16332
miR-205: 406988
miR-2137: 100316779"
  },
  {
    "caption": "(C) BMDMs were transfected with scrambled miRNA mimic (40 nM), miR-2137 mimic (40 nM) and miR-205 mimic (40 nM) for 48 hours and protein lysates were analyzed by western blotting using specific antibodies for INPPL1 and β-actin. Protein quantifications are displayed in graph next to the blots (n=3 biological replicates).",
    "ncbi_link": "miR-205: 406988
miR-2137: 100316779"
  },
  {
    "caption": "(D) BMDMs were transfected with negative control antagomir (200 nM) or miR-2137 antagomir (200 nM) for 24 hours, followed by PA (500 µM) treatment for 9 hours. Protein lysates were analyzed by western blotting using specific antibodies for INPPL1 and β-actin. Protein quantifications shown in the graph next to blots (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779"
  },
  {
    "caption": "(A-C) BMDMs were transfected with scrambled miRNA mimic (40 nM), miR-2137 mimic (40 nM) or miR-205 mimic (40 nM) for 24 hours and cells were processed for lipidomics analysis as described in materials and methods section. The ratio of lipids from this analysis is shown for (A) PI(3,4,5)P3 to PIP2.; (B) PI(3,4,5)P3 to PI; (C) PI(3,4,5)P3 to PIP. Data from LC/MS/MS using a Waters Xevo TQ-S MS/MS in MRM mode represent mean values ± SEM of peak areas normalized to internal standards as described in Methods. (n=3 biological replicates)",
    "ncbi_link": "miR-205: 406988
miR-2137: 100316779"
  },
  {
    "caption": "BMDMs were transfected with (D) scrambled miRNA mimic (40 nM) or miR-2137 mimic (40 nM) for 48 hours and protein lysates were analyzed by western blotting using specific antibodies against INPPL1, pAKTS473, AKT, p70S6KT389, p70S6K, pS6S235/236, S6, p4E-BP1S65, 4E-BP1, pmTORS2448, mTOR and β-actin. Protein quantifications are shown next to the western blots (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779"
  },
  {
    "caption": "BMDMs were transfected (E) with control antagomir (200 nM) or miR-2137 antagomir for 24 hours and protein lysates were analyzed by western blotting using specific antibodies against INPPL1, pAKTS473, AKT, p70S6KT389, p70S6K, pS6S235/236, S6, p4E-BP1S65, 4E-BP1, pmTORS2448, mTOR and β-actin. Protein quantifications are shown next to the western blots (n=3 biological replicates).",
    "ncbi_link": "miR-2137: 100316779"
  },
  {
    "caption": "The presence of GFP-PSF-1 on mitotic chromatin (indicated by white arrows) was monitored by spinning disk confocal microscopy (see Materials and Methods), in GFP-psf-1 mCherry-Histone H2B worms that were fed on bacteria containing a single plasmid expressing the indicated RNAi treatments ('Control' = empty vector). NEB = nuclear envelope breakdown. The scalebars correspond to 5 µm.",
    "ncbi_link": "mCherry: 
Histone H2B: 175029
psf-1: 187885"
  },
  {
    "caption": "Similar experiment comparing the impact of RNAi inactivation of lrr-1, tim-1 and tipn-1 upon CMG-MCM-7 ubiquitylation and the association of CUL-2LRR-1 with the worm replisome. Asterisks indicate non-specific bands in the immunoblots.",
    "ncbi_link": "lrr-1: 173869
tim-1: 176652
tipn-1: 171803"
  },
  {
    "caption": "Analogous experiment to that in (A), but with worms fed on the indicated proportions of bacteria expressing ubxn-3 RNAi, in combination with 20% bacteria expressing tim-1 RNAi specific for tim-1, plus the required remainder of bacteria containing empty vector (to make a total of 100%).",
    "ncbi_link": "tim-1: 176652
ubxn-3: 173407"
  },
  {
    "caption": "Correlation between IKBKE mRNA levels (log2 ratio) and immune signature (Yoshihara et al, 2013) in the METABRIC transcriptomic dataset from 1981 breast cancer patients (Curtis et al, 2012). Pearson's correlation rho coefficient and significance of difference from slope = 0 (p) are shown. IKBKE gene copy number and mRNA levels (log2 ratio) from the METABRIC transcriptomic dataset (see D) are plotted. Estimated +1 copy number values are shown by the dotted vertical line. No significant correlation by Pearson's correlation rho coefficient and significance of difference from slope = 0 (p) was detected.",
    "ncbi_link": "IKBKE: 9641"
  },
  {
    "caption": "IKBKE gene (encoding for IKKε) was deleted in MCF10A cells via CRISPR-Cas9 technology. 3 knockout clones were combined for each cell line. IKKε CRISPR-Cas9 knockout MCF10A cells form less colonies when grown in soft agar with macrophage-conditioned medium for 5 weeks compared to CRISPR-Cas9 control (nontargeting crRNA) cells. Colonies ≥ 50 μm were counted. Error bars represent mean ± SEM from 3 independent experiments (n=3 per condition). Media from two macrophage donors were combined in 1:1 ratio in each experiment. Macrophage donors are indicated as M1A - M1 activated, M2A - M2 activated macrophages.",
    "ncbi_link": "IKBKE: 9641"
  },
  {
    "caption": "IKBKE gene (encoding for IKKε) was deleted in MCF10A cells via CRISPR-Cas9 technology. 3 knockout clones were combined for each cell line. 16-days old MCF10A spheroids grown in matrigel/collagen mix were stimulated for 24h with either macrophage-conditioned or control medium. IKKε CRISPR-Cas9 knockout MCF10A cells are less invasive compared CRISPR Control (nontargeting crRNA) cells. Error bars represent mean ± SEM from 3 independent experiments (n=3 per condition). Media from two macrophage donors were combined in 1:1 ratio in each experiment. Macrophage donors are indicated as M1A - M1 activated, M2A - M2 activated macrophages.",
    "ncbi_link": "IKBKE: 9641"
  },
  {
    "caption": "Correlation of mRNA levels of the SBP enzyme genes PSAT1 (E), PHGDH (F), PSPH (G) with the immune signature (Yoshihara et al, 2013) in the METABRIC transcriptomic dataset from 1981 breast cancer patient (Curtis et al, 2012).",
    "ncbi_link": "PHGDH: 26227
PSAT1: 29968
PSPH: 5723"
  },
  {
    "caption": "PHGDH gene was deleted in MCF10A cells via CRISPR-Cas9 technology. 3 knockout clones were combined for each cell line. PHGDH CRISPR-Cas9 knockout MCF10A cells form less colonies when grown in soft agar with macrophage-conditioned medium for 5 weeks compared to CRISPR-Cas9 control (nontargeting crRNA) cells. Colonies ≥ 50 μm were counted. Error bars represent mean ± SEM from 3 independent experiments (n=3 per condition). Media from two macrophage donors were combined in 1:1 ratio in each experiment. Macrophage donors are indicated as , M1A - M1 activated, M2A - M2 activated macrophages.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "PHGDH gene was deleted in MCF10A cells via CRISPR-Cas9 technology. 3 knockout clones were combined for each cell line. 16-days old MCF10A spheroids grown in matrigel/collagen mix were stimulated for 24h with either macrophage-conditioned or control medium. PHGDH CRISPR-Cas9 knockout MCF10A cells are less invasive compared CRISPR Control (nontargeting crRNA) cells. Error bars represent mean ± SEM from 3 independent experiments (n=3 per condition). Media from two macrophage donors were combined in 1:1 ratio in each experiment. Macrophage donors are indicated as M1A - M1 activated, M2A - M2 activated macrophages.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Wild-type mice on HFD gain more weight compared to ND mice. *p < 0.05 by one-tailed students t-test.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Average adipocytes size (major diameter) in mammary fat pads is larger in HFD mice compared to ND mice based on the analysis of at least 100 adipocytes per mice on H&E stained sections. *p < 0.05 by two-tailed students t-test.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). The number of F4/80+ macrophages in mammary fat pads is increased in HFD mice compared to ND mice. The average of F4/80+ macrophages in at least 10 fields of view per mouse is shown. *p < 0.05 by two-tailed students t-test.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Mice were administered amlexanox (17 mM) or vehicle control daily by oral gavage (Reilly et al, 2013). A control group (wild-type mice) was also included to confirm the efficacy of the diet and to control for possible unpredicted interactions of the MMTV-PyMT gene. PyMT-MMTV+/- mice on HFD gain more weight compared to ND mice. *p < 0.05 by one-tailed students t-test. Amlexanox does not affect weight gain either in mice on F) ND or G) HFD.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "A-J)Ten per group female C57Bl/6 mice heterozygous for the PyMT-MMTV started high fat diet (HFD) when 6-7 weeks old (prior of mammary tumour development) together with control mice on normal diet (ND; n=10). Mice were administered amlexanox (17 mM) or vehicle control daily by oral gavage (Reilly et al, 2013). A control group (wild-type mice) was also included to confirm the efficacy of the diet and to control for possible unpredicted interactions of the MMTV-PyMT gene. Mammary tumours are developing earlier in PyMT-MMTV+/- mice on HFD compared to ND mice. Amlexanox does not affect tumour development in PyMT-MMTV+/- mice on ND, but delays tumour formation in J) HFD mice.",
    "ncbi_link": "PyMT: "
  },
  {
    "caption": "B RIPK1 is dispensable for apoptosis  induction by LBW242  and VCR. LOUCY  cells were transfected with a non-targeting siRNA (neg-siRNA) or a RIPK1-specific siRNA. 6h post transfection, cells were treated with the indicated drugs and apoptosis  was measured 40h thereafter. Mean ± SD of 3 independent experiments is shown; *** p<0.001 by unpaired Student's t-test. Knockdown (KD) was verified by Western blot at the time of apoptosis  measurement and KD efficiency calculated compared to the control. One representative immunoblot  out of 3 biological replicates is shown.",
    "ncbi_link": "RIPK1: 8737"
  },
  {
    "caption": "D KD of NEMO  does not affect the SM-mediated sensitization to chemotherapy-induced apoptosis. Experiment was performed as described in B, except that an siRNA targeting NEMO  was used. Mean ± SD of 3 independent experiments is shown; * p<0.05 by unpaired Student's t-test.",
    "ncbi_link": "NEMO: 8517"
  },
  {
    "caption": "F KD of RelB does not inhibit apoptosis. Experiment was performed as described in B, except that an siRNA targeting RelB was used. Mean ± SD of 3 independent experiments is shown; differences are not significant, by unpaired Student's t-test.",
    "ncbi_link": "RelB: 5971"
  },
  {
    "caption": "A Expression  of XIAP  mRNA in samples obtained from BM  of healthy individuals (Ctrl, n=10) or patients  with AML  (n=517) or ALL  (n=306). Data are expressed as median, 25th and 75th percentile, whiskers indicate min/max; ** p<0.01; **** p<0.0001 by Games-Howell post-hoc test.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "Parental and XIAP  over-expressing  NALM-6 cells (C) were treated with VCR apoptosis  (Annexin-V  / PI) was measured at the indicated  time points (C) by  flow cytometry. Mean ± SEM of 3 independent experiments is shown; **** p ≤0.0001 by unpaired Student's t-test. XIAP   protein level was analyzed in parental and XIAP-overexpressing NALM-6 cells by protein immunoassay (Simple Western); Actin  was used as loading control. One representative immunoassay out of 3 independent experiments is shown.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "D Parental and XIAP  over-expressing REH  cells (D) were treated with VCR  or LBW242; apoptosis  (Annexin-V / PI) was measured after 72h (D) by  flow cytometry. Mean ± SEM of 3 independent experiments is shown; **** p ≤0.0001 by unpaired Student's t-test. XIAP  protein level was analyzed by protein immunoassay (Simple Western); Actin  was used as loading control. One representative immunoassay out of 3 independent experiments is shown.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "B shRNA expression control. Equal expression levels of  ds-RED in the sh-CTRL/mTagBFP and sh-XIAP/eGFP  subpopulation indicates identical expression levels of control and XIAP  shRNA. One representative histogram out of 3 independent experiments is shown.",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "C Expression of IAP. Western blot analysis of XIAP  in NALM-6 cells expressing sh-CTRL/mTagBFP or sh-XIAP/eGFP  under the SFFV  promoter; GAPDH  was used as loading control. One representative immunoblot  out of 3 independent experiments is shown.",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "D  Western blot analysis of NALM-6  cells with moderate (69%, EF1α  promoter) or strong (92%, SFFV   promoter) KD of XIAP; GAPDH  was used as loading control. The XIAP  KD levels (% KD) were quantified relative to sh-CTRL. One representative immunoblot  out of 3 independent experiments is shown.",
    "ncbi_link": "EF1α: 1915
XIAP: 331"
  },
  {
    "caption": "F Moderate knockdown of XIAP  sensitizes towards chemotherapy. NALM-6 cells expressing sh-CTRL/mTagBFP or sh-XIAP/eGFP were mixed at a 1:1 ratio and injected into groups of mice. 4 days after injection, mice  were either treated with PBS  (n=4), or with Vincristin  (VCR, n=8), 0.3mg/kg i.v. once a week for 3 consecutive weeks. 7 days after last treatment, mice  were sacrificed, and relative proportion of sh-CTRL and sh-XIAP  subpopulations re-isolated from the BM  was quantified by flow cytometry. Data are depicted as mean ± SEM of all mice analyzed with **** p ≤0.0001 by unpaired Student's t-test with Welch's correction.",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "G Strong knockdown of XIAP  impairs  NALM-6 growth in vivo. NALM-6  cells expressing sh-CTRL/mTagBFP or sh-XIAP/eGFP were mixed at a 1:1 ratio and injected into groups of mice  (n=8). 38 or 46 days after injection, mice  were sacrificed, and relative proportion of sh-CTRL and sh-XIAP subpopulations re-isolated from the BM was quantified by flow cytometry. Data are depicted as mean ± SEM of all mice analyzed with **** p ≤0.0001 by unpaired Student's t-test.",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "H PARP  cleavage in NALM-6 cells with strong XIAP  inhibition. NALM-6 cells were lentivirally  transduces with sh-CTRL or sh-XIAP  (SFFV). 4 days later, cells were lysed and relative cleavage level of PARP  (%) was analyzed by protein immunoassay (Simple Western). Mean ± SD of 3 independent experiments is shown; ** p <0.01 by unpaired Student's t-test.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "I XIAP  reconstitution in NALM-6 cells. NALM-6 cells were transduced with shCTRL, shXIAP.1 alone or shXIAP.1 together with the XIAP  overexpression vector. At day 0, transduced cells were mixed in a 1:1 ratio with parental (untransduced) NALM-6  cells. Distribution of the fluorochrome marker was used as a readout to determine growth  variations of the respective subpopulation over time. Mean ± SD of 3 independent experiments is shown; ** p <0.01 by unpaired Student's t-test.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "XIAP  plays an essential role for  ALL-265 growing in mice. Experimental scheme and stability of XIAP  knockdown over passaging. ALL-265 PDX cells produced as described in A were mixed at a 1:1 ratio and injected into mice  (P1, n=4). At clinical signs of illness, cells were isolated and re-injected into next recipient mice  (P2, n=4). XIAP  expression levels of P1 and P2 PDX cells expressing sh-CTRL/mTagBFP or sh-XIAP/eGFP  were analyzed by Western blot  at the end of each passage; GAPDH  was used as loading control (B).",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "XIAP  plays an essential role for ALL-265 growing in mice.  ALL-265 PDX cells produced as described in A were mixed at a 1:1 ratio and injected into mice  (P1, n=4). At clinical signs of illness, cells were isolated and re-injected into next recipient mice  (P2, n=4). Relative proportion of ALL-265 GEPDX cells expressing sh-CTRL/mTagBFP or sh-XIAP/eGFP  re-isolated from the BM  at the end of each passage was quantified by  flow cytometry  (C). Data are depicted as mean ± SEM of all mice  analyzed (n=4, each passage) with **** p<0.0001 by unpaired Student's t-test.",
    "ncbi_link": "eGFP: 
mTagBFP: 
XIAP: 331"
  },
  {
    "caption": "D Dose-response  relationship between strength of XIAP  knockdown and growth  disadvantage;  ALL-265 PDX cells of a representative mouse  were analyzed separately for dsRED/shRNA high and low expressing cells.",
    "ncbi_link": "dsRED: 
XIAP: 331"
  },
  {
    "caption": "One-week-old mosquitoes  were thoracically  infected with DENV2-Asian I  (A), DENV2-Asian American (B), DENV3-I mutants, respectively. A. aegypti mosquitoes  were infected intrathoracically with 10 p.f.u. of DENV. The DENV  viral loads were assessed at 3 days postinfection via  qRT-PCR and were normalized against  A. aegypti actin. Data information: one dot represents one mosquito, and the horizontal lines represent the median of the results. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "actin: 5572986"
  },
  {
    "caption": "One-week-old mosquitoes  were thoracically  infected with DENV4-I  (D) mutants, respectively. A. aegypti mosquitoes  were infected intrathoracically with 10 p.f.u. of DENV. The DENV viral loads  were assessed at 3 days postinfection via qRT-PCR  and were normalized against  A. aegypti actin. Data information: one dot represents one mosquito, and the horizontal lines represent the median of the results. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "actin: 5572986"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia  detection from Day 1 to Day 7. The  viral loads from AG6 mice  infected with DENV2-Asian I  (E), were measured by qRT-PCR and were normalized against mouse GAPDH. Data information: n = 6 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia   detection from Day 1 to Day 7. The  viral loads from AG6 mice  infected with DENV2-Asian American (F), DENV3-I (G) were measured by  qRT-PCR  and were normalized against mouse GAPDH. Data information: , n = 6 biological replicates. In (F), n = 5 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "Four-week-old AG6 mice  were infected with DENV (2,500 p.f.u.) by footpad  inoculation. Blood  samples were collected for DENV viremia   detection from Day 1 to Day 7. The viral loads from AG6 mice  infected with DENV4-I  (H) were measured by qRT-PCR  and were normalized against mouse GAPDH. Data information: n = 6 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the Mann-Whitney test The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "I, J Infection  of DENV2-Asian I  mutants on  hu-moDC  (I) and  hu-moMØ  (J). The cells were infected with 0.01 MOI of the indicated viruses. The infected cells were detected at 48 h postinfection by  qRT-PCR, and DENV viral loads were normalized against human GAPDH. Data information: n = 6 biological replicates. data are presented as mean ± SEM. The data were analyzed statistically using the unpaired t-test (I, J). The P value represents a comparison between the mutants and corresponding WT within genotypes. *p < 0.05, **p < 0.01, ***p < 0.001, n.s., not significant (p > 0.05).",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "B The 293T  cells were transfected with a pcDNA3.1 recombinant plasmid with a human DC-SIGN gene. The cells transfected by an empty pcDNA3.1 plasmid served as negative controls. Thirty-six hours after transfection, the cells were infected with DENV2  (0.01 MOI). The DENV2 viral loads were assessed at 48 h postinfection via qRT-PCR and were normalized against human GAPDH. Data information: In (B), n = 6 biological replicates. In (B, the data are presented as means ± SEM and were analyzed statistically using an unpaired t-test. The P value represents a comparison between the mutants and the 16681 WT strain. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, n.s., not significant (p > 0.05). ",
    "ncbi_link": "DC-SIGN: 30835
GAPDH: 2597"
  },
  {
    "caption": "A RNF123 suppresses the SeV- and EMCV-induced but not the cGAS and STING-mediated activation of the IFN-βpromoter. HEK293T cells (3×105) were transfected with the IFN-β reporter plasmid (100 ng), the pRL-TK Renilla luciferase plasmid (100 ng), the expression plasmid for cGAS (50 ng) and STING (50 ng) or empty vector (100 ng), and 0, 20, 50, or 100 ng (wedges) of RNF123 for 12 h, and then were infected with SeV or EMCV or left uninfected. Luciferase assays were performed after 18 h and results are presented relative to the luciferase activity in control cells.",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
IFN-β: 3456
cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "B RNF123 inhibits the SeV-, but not the cGAS and STING-induced activation of the NF-κB promoter. HEK293T cells (3×105) were transfected with the NF-κB reporter plasmid (100 ng), the pRL-TK Renilla luciferase plasmid (100 ng), the expression plasmids for cGAS (50 ng) and STING (50 ng), or empty vector (100 ng), and 0, 20, 50 or 100 ng (wedges) of RNF123 for 12 h, and were then infected for 24 h with SeV or left uninfected, followed by analysis as described in A.",
    "ncbi_link": "Renilla luciferase: 
cGAS: 115004
NF-κB: 4791///4790
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "C, D RNF123 inhibits the SeV-induced, but not the cGAS and STING-mediated RANTES and IFN-β transcription. The transfection and treatment were as in A. Total RNA was isolated and RT-PCR (C) was performed using the indicated primers.",
    "ncbi_link": "RANTES: 6352
IFN-β: 3456
cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "C, D RNF123 inhibits the SeV-induced, but not the cGAS and STING-mediated RANTES and IFN-β transcription. The transfection and treatment were as in A. Total RNA was isolated and Q-PCR (D) was performed using the indicated primers.",
    "ncbi_link": "IFN-β: 3456
cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "E RNF123 inhibits the SeV-induced, but not the cGAS and STING-mediated IFN-β secretion. The transfection and treatment were as in A. Bioassays for type I interferon in the supernatants of HEK293T cells were performed and the results are presented relative to untreated control cells.",
    "ncbi_link": "cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "F Overexpression of RNF123 enhances NDV-eGFP replication. HEK293T cells (1×105) were transfected with the expression plasmids for Flag-RNF123 or empty vector (2 µg). At 24 h after transfection, cells were infected with NDV-eGFP. At 30 h after infection, viral replication was determined by GFP expression visualized by fluorescence microscopy and analyzed by western blot.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "G RNF123 enhances EMCV replication. HeLa cells (1×105) were transfected with the expression plasmids for Flag-RNF123 or empty vector (2 µg). At 24 h after transfection, cells were infected with EMCV or given DMEM with no virus. At 18 h after infection, viral replication was determined by VP1 expression, which was analyzed by western blot.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "A HEK293T cells with stable knockdown of RNF123 were generated using shRNA. Western blot was performed with anti-RNF123, anti-VISA (as a control), and anti-GAPDH antibodies after infection with five lentiviruses encoding a shRNA control (GFPsh) and four shRNAs targeting RNF123 (RNF123 sh #1, #2, #3, and #4) in HEK293T cells.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "B, C Knockdown of RNF123 facilitated the activation of IFN-β and NF-κB promoters induced by SeV and EMCV but not by cGAS and STING. Stable HEK293T cells with GFPsh or RNF123 shRNAs (2×105) were transfected with the indicated reporter plasmid (100 ng), pRL-TK Renilla luciferase plasmid (100 ng), cGAS (50 ng), and STING (50 ng), or empty vector (100 ng). At 12 h after transfection, they were infected for 12 h with SeV or EMCV or left uninfected, followed by analysis as described in the legend of Fig 1A.",
    "ncbi_link": "Renilla luciferase: 
IFN-β: 3456
cGAS: 115004
NF-κB: 4791///4790
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "D, E Knockdown of RNF123 enhances the IFN-β and RANTES transcription induced by SeV and EMCV, but not that by cGAS and the STING. HEK293T cells were transfected with cGAS (1 μg) and STING (1 μg) or empty vector for 12 h, and then infected with SeV or EMCV for 12 h or left uninfected. Total RNA was isolated and RT-PCR (D) were performed using the indicated primers.",
    "ncbi_link": "RANTES: 6352
IFN-β: 3456
cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "D, E Knockdown of RNF123 enhances the IFN-β and RANTES transcription induced by SeV and EMCV, but not that by cGAS and the STING. HEK293T cells were transfected with cGAS (1 μg) and STING (1 μg) or empty vector for 12 h, and then infected with SeV or EMCV for 12 h or left uninfected. Total RNA was isolated and Q-PCR (E) were performed using the indicated primers.",
    "ncbi_link": "IFN-β: 3456
cGAS: 115004
RNF123: 63891
STING: 340061"
  },
  {
    "caption": "F, G Time-course of potentiation of SeV-induced IFN-β transcription (F) by knockdown of RNF123. HEK293T cells were infected with SeV for 6, 12, 18, or 24 h, total RNA was isolated, and RT-PCR was performed using the indicated primers (F).",
    "ncbi_link": "IFN-β: 3456
RNF123: 63891"
  },
  {
    "caption": "F, G Time-course of potentiation of SeV-induced IFN-β secretion (G) by knockdown of RNF123. HEK293T cells were infected with SeV for 6, 12, 18, or 24 h, total RNA was isolated. Bioassays of type-I interferon in the supernatants of HEK293T cells were performed, and the results are presented relative to untreated control cells (G).",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "H HeLa cells with stable knockdown of RNF123 were generated by shRNA. Western blot was performed as described in Fig 2A.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "I, J Knockdown of RNF123 enhances SeV- and EMCV- induced IFN-β expression in HeLa cells. HeLa cells were infected with SeV or EMCV for 12 h, total RNA was isolated, and RT-PCR (I) was performed using the indicated primers.",
    "ncbi_link": "IFN-β: 3456
RNF123: 63891"
  },
  {
    "caption": "I, J Knockdown of RNF123 enhances SeV- and EMCV- induced IFN-β expression in HeLa cells. HeLa cells were infected with SeV or EMCV for 12 h, total RNA was isolated, and Q-PCR (J) was performed using the indicated primers.",
    "ncbi_link": "IFN-β: 3456
RNF123: 63891"
  },
  {
    "caption": "K Knockdown of RNF123 suppresses NDV-eGFP replication. HEK293T cells (2×105) were infected with NDV-eGFP. At 30 h after infection, viral replication was determined by GFP expression visualized by fluorescence microscopy and analyzed by western blot with GFP antibody.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "L Knockdown of RNF123 inhibits EMCV replication. HeLa cells (2×105) were infected with EMCV for 0, 12, or 18 h.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "A, B RNF123 inhibits the activation of the IFN-β (A) promoters induced by the overexpression of RIG-I, RIG-I CARD, MDA5 CARD, and VISA, but has no effect on the TBK1- and IRF3-5D-induced activation of the IFN-β promoter (A) . HEK293T cells (2×105) were transfected with the indicated plasmids (100 ng), IFN-β promoter luciferase plasmid (100 ng), and pRL-TK Renilla luciferase plasmid (100 ng), together with an empty vector and RNF123 construct (100 ng). Luciferase assays were performed 24 h after transfection.",
    "ncbi_link": "Renilla luciferase: 
RIG-I: 23586
MDA5: 64135
IFN-β: 3456
IRF3: 3661
VISA: 57506
RNF123: 63891
TBK1: 29110"
  },
  {
    "caption": "A, B RNF123 inhibits the activation of the NF-κB (B) promoters induced by the overexpression of RIG-I, RIG-I CARD, MDA5 CARD, and VISA, but has no effect on the TAB2- and IKKβ-induced activation of the NF-κB promoter (B). HEK293T cells (2×105) were transfected with the indicated plasmids (100 ng), NF-κB promoter luciferase plasmid (100 ng), and pRL-TK Renilla luciferase plasmid (100 ng), together with an empty vector and RNF123 construct (100 ng). Luciferase assays were performed 24 h after transfection.",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
RIG-I: 23586
MDA5: 64135
IKKβ: 3551
NF-κB: 4791///4790
RNF123: 63891
TAB2: 23118"
  },
  {
    "caption": "C Knockdown of RNF123 potentiates the activation of the IFN-β promoter induced by RIG-I, RIG-I CARD, MDA5, and MDA5 CARD, but not that by VISA, TBK1, and cGAS/STING. 293T-GFPsh, shRNF123 #1, #3, and #4 stable cell pools (2×105) were transfected with the indicated plasmids. Luciferase assays were performed 24 h after transfection.",
    "ncbi_link": "RIG-I: 23586
MDA5: 64135
IFN-β: 3456
VISA: 57506
cGAS: 115004
RNF123: 63891
TBK1: 29110
STING: 340061"
  },
  {
    "caption": "D RNF123 interacted with RIG-I and MDA5, but not VISA, TBK1, and cGAS. HEK293T cells (1×106) were transfected with Flag-RNF123 (F-RNF123) together with HA-RIG-I, HA-MDA5, HA-VISA, HA-TBK1, or HA-cGAS plasmids (8 μg each). Cell lysates were immunoprecipitated (IP) with anti-HA (αHA). The immunoprecipitates were analyzed by western blotting (immunoblotting [IB]) with anti-Flag (αF) or anti-HA antibody (αHA). Whole-cell lysates (WCL) were analyzed by western blotting with anti-HA and anti-Flag antibodies to determine the expression levels of transfected plasmids.",
    "ncbi_link": "RIG-I: 23586
MDA5: 64135
VISA: 57506
cGAS: 115004
TBK1: 29110"
  },
  {
    "caption": "B The SPRY and coiled-coil domains are both indispensable for inhibiting IFN-β promoter activation. HEK293T cells (3×105) were transfected with the IFN-β reporter plasmid (100 ng), the pRL-TK Renilla luciferase plasmid (100 ng), the expression plasmid for RNF123 and its mutants (100 ng), and the empty vector or RIG-I CARD/MDA5 CARD (100 ng). Reporter assays were performed 24 h after transfection.",
    "ncbi_link": "Renilla luciferase: 
RIG-I: 23586
MDA5: 64135
IFN-β: 3456
RNF123: 63891"
  },
  {
    "caption": "C The SPRY domain and two coiled-coil domains of RNF123 are both required for interaction with RIG-I CARD. HEK293T cells (1×106) were transfected with HA-RIG-I CARD together with F-RNF123 or its mutants (8 μg each). Cell lysates were immunoprecipitated (IP) with anti-Flag (α-F). The immunoprecipitates were analyzed by western blotting (immunoblotting [IB]) with anti-HA (α-HA) or anti-Flag (α-F). Whole-cell lysates (WCL) were analyzed by western blotting with anti-HA and anti-Flag antibodies.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "D KPC2 has no effect on the activation of the IFN-β reporter induced by RIG-I CARD and MDA5 CARD. HEK293T cells (3×105) were transfected with the IFN-β reporter plasmid (100 ng), the pRL-TK Renilla luciferase plasmid (100 ng), and the indicated expression plasmids. Reporter assays were performed 24 h after transfection.",
    "ncbi_link": "Renilla luciferase: 
RIG-I: 23586
MDA5: 64135
IFN-β: 3456
KPC2: 10422"
  },
  {
    "caption": "E Effect of shKPC2 plasmids on endogenous KPC2. RT-PCR was performed with the indicated primers after HEK293T cells were infected with six lentiviruses encoding an shRNA control (GFPsh) and five shRNAs targeting kpc2 (Kpc2 #1-#5).",
    "ncbi_link": "KPC2: 10422
kpc2: 10422
Kpc2: 10422"
  },
  {
    "caption": "F KPC2 is not required for the inhibitory action of RNF123. HEK293T cells (2×105) with GFPsh or KPC2 sh (#1, #2, or #4) were transfected with the IFN-β reporter plasmid (100 ng) and the pRL-TK Renilla luciferase plasmid (100 ng) with the empty vector or RNF123 (100 ng). Twenty-four hours after transfection, cells were infected with SeV or left uninfected. Reporter assays were performed 18 h after infection.",
    "ncbi_link": "Renilla luciferase: 
IFN-β: 3456
RNF123: 63891
KPC2: 10422"
  },
  {
    "caption": "G Knockdown of KPC2 had no effect on SeV-induced IFN-β expression. HEK293T cells with GFPsh or KPC2 sh #4 were infected with SeV for the indicated times, total RNA was isolated, and RT-PCR experiments were performed.",
    "ncbi_link": "IFN-β: 3456
KPC2: 10422"
  },
  {
    "caption": "A, B RNF123 interacts with RIG-I/MDA5 CARD. HEK293T cells (1×106) were transfected with expression plasmids for Flag-RNF123 together with HA-RIG-I or its truncations (8 μg each). Co-immunoprecipitation and whole-cell lysates were analyzed as described in the legend of Fig. 3D.",
    "ncbi_link": "RIG-I: 23586
MDA5: 64135"
  },
  {
    "caption": "C, D RNF123 competes with VISA for RIG-I/MDA5 CARD binding. HEK293T cells (1×106) were transfected with expression plasmids for HA-RIG-I CARD/MDA5 CARD alone or together with Flag-VISA or with Flag-VISA and Flag-RNF123 (8 μg each). Co-immunoprecipitation and whole-cell lysates were analyzed as described in Fig. 3D.",
    "ncbi_link": "RIG-I: 23586
MDA5: 64135
VISA: 57506
RNF123: 63891"
  },
  {
    "caption": "E RNF123 does not compete with REUL for RIG-I CARD binding. The methods of transfection and co-immunoprecipitation were as described in Fig. 5C,D.",
    "ncbi_link": "RNF123: 63891
REUL: 84282"
  },
  {
    "caption": "F Knockdown of RNF123 facilitates the endogenous interaction between RIG-I and VISA in 293T cells. 293T cells stably infected with SeV were treated for the indicated times. Cell lysates were immunoprecipitated with anti-VISA antibody. The immunoprecipitates and lysates were analyzed by western blotting with the indicated antibody.",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "G Knockdown of RNF123 facilitates the endogenous interaction between MDA5 and VISA in HeLa cells. HeLa cells were stably infected with EMCV for the indicated times. Co-immunoprecipitation and whole-cell lysates were analyzed as described in (F).",
    "ncbi_link": "RNF123: 63891"
  },
  {
    "caption": "C) 8 weeks old C57BL/6N male mice were fasted (food removed at ZT 12) or re-fed (fasted from ZT4 to ZT12 for synchronization; food re-introduced at ZT 12). Tissue samples were collected at ZT 12, 15, 18 and 21 (n=4). Liver lysates analyzed by immunoblotting using anti-Prox1 and anti-P_S6K(Thr389) antibodies; β actin was detected as an input control. The quantification of SUMOylated Prox1 (%) and total Prox1 protein expression as well as Prox1 mRNA levels analyzed by qPCR are shown. qPCR data is presented as relative fold change normalized to the housekeeping gene TBP. Data information: Every dot represents one individual mouse. Data: mean ±SEM. Significance was determined by one-way ANOVA with Dunnett´s multiple comparison test relative to samples collected at ZT 12. *** P≤0.001.",
    "ncbi_link": "Prox1: 19130
TBP: 21374"
  },
  {
    "caption": "B) HepG2 cells overexpressing HA-tagged mouse wild-type Prox1 (wt), Prox1 K556R mutant or Prox1 E558A mutant. Cell lysates analyzed by immunoblotting using anti-HA antibodies; tubulin was detected as an input control.",
    "ncbi_link": "HA: 
Prox1: 19130"
  },
  {
    "caption": "B) 8 weeks old Prox1K556R K.I. (f/f) male mice were injected with a control AAV (Ctrl_AAV), with an AAV to overexpress Cre recombinase (Cre_AAV) or with phosphate-buffered saline (PBS) (n=4). Liver tissue samples were collected 3 weeks later from mice fed ad libitum. Liver lysates were analyzed by immunoblotting using anti-Prox1 and anti-Cre antibodies; Vcp was detected as an input control. The quantification of SUMOylated Prox1 and total Prox1 protein expression as well as Prox1 mRNA levels analyzed by qPCR are shown. qPCR data presented as relative fold change normalized to the housekeeping gene TBP. Data information: (B) Every dot represents one individual mouse. Data: mean ±SEM. Significance was determined by one-way ANOVA with Tukey´s multiple comparison test between groups. *** P≤0.001, **** P≤0.0001.",
    "ncbi_link": "Cre: 2777477
Prox1: 19130
TBP: 21374"
  },
  {
    "caption": "A) 8 weeks old Prox1K556R K.I. (f/f) male mice were injected with a control AAV (Ctrl_AAV) or with an AAV to overexpress Cre recombinase (Cre_AAV) and placed on a high-fat (45%) high-fructose (20% w/v) diet for 18 weeks. Liver samples were collected between ZT 16 and 17 in the fasted (8 h) and re-fed (fasted 8 h and re-fed 4-5 h) states (n=7-8). Liver lysates were analyzed by immunoblotting using anti-Prox1 and anti-Cre antibodies; β actin was detected as an input control. The quantification of SUMOylated Prox1 and total Prox1 protein expression are shown. Data information Every dot represents one individual mouse. Data: mean ±SEM. Significance was determined by two-way ANOVA with Sidak´s multiple comparison test between different groups and conditions. * P≤0.05, ** P≤0.01, **** P≤0.0001.",
    "ncbi_link": "Cre: 2777477
Prox1: 19130"
  },
  {
    "caption": "C) Heatmap displaying the expression of enriched genes involved in phase I, II and III of bile acid detoxification and bile acid synthesis in the liver of obese mice expressing the Prox1 K556R mutant (Cre_AAV) in comparison to obese mice expressing wild-type Prox1 (Ctrl_AAV) in the fasted state (n=4). The occupation scores according to a published Chip- sequencing analysis on Prox1 Cyp7a1 was used as a reference gene.",
    "ncbi_link": "Cre: 2777477
Cyp7a1: 13122
Prox1: 19130"
  },
  {
    "caption": "D) Prox1/LRH-1 co-immunoprecipitation in HEK293A cells overexpressing HA-tagged Prox1 wild-type (wt) or K556R mutant (KR) and Myc-tagged LRH-1.",
    "ncbi_link": "HA: 
Myc: 
LRH-1: 26424
Prox1: 19130"
  },
  {
    "caption": "C The parental population and the NFR resistant clones were analyzed for eEF2K mRNA expression by real-time PCR relative to β-actin (mean and s.e.m. from 3 independent batches of cells are shown). P values were calculated using 1way ANOVA analysis of variance followed by Dunnett's multiple comparison tests. *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001.",
    "ncbi_link": "β-actin: 
eEF2K: 29904"
  },
  {
    "caption": "B eEF2K WT and KO MEF treated for 6h with indicated concentration of NFR, 200 nM rapamycin (Rapa.), 1h starvation (Starv.) or 1 mM of the AMPK activator AICAR, were analyzed by immunoblot with antibodies directed against total or phosphorylated eEF2 (Thr56).",
    "ncbi_link": "eEF2K: 13631"
  },
  {
    "caption": "B eEF2K WT and KO MEF treated for 6h with indicated concentration of NFR, Rapamycin (Rapa), AICAR or starved for indicated time in PBS (Starv.), were analyzed by immunoblot using indicated antibodies. Tubulin is used as loading control.",
    "ncbi_link": "eEF2K: 13631"
  },
  {
    "caption": "D NFR-mediated eEF2 phosphorylation is not affected in AMPKα1α2 dKO. AMPKα1α2 WT and dKO MEF treated for 6h with indicated concentration of NFR, Rapamycin (Rapa), AICAR or starved for 1h in PBS (Starv.), were analyzed by immuoblot with indicated antibodies. * anti-total AMPKα antibody give an unspecific band with a slightly higher molecular weight in dKO cells. Tubulin is used as loading control. Each panel is representative of at least 3 independent experiments.",
    "ncbi_link": "AMPKα1: 105787"
  },
  {
    "caption": "A-B EEF2K contributes to the decreased translation observed with NFR without impacting translation in presence of TM. A. Quantification of newly synthesized proteins at 0, 2, 4 and 6h after 20 μM NFR (left panels) or 10 μg/ml TM (right panels) treatment in MEF eEF2K +/+ and eEF2K-/-. Treated cells were labeled for 15 minutes with 35S-methionine and visualized by SDS PAGE and subsequent autoradiography. Autoradiographies from four different experiments (see also source data) were quantified and results show percentage of translation compared to untreated cells. The mean and s.e.m of four independent metabolic labeling experiments are shown. *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001 obtained using 2way ANOVA analysis of variance (in red) followed by Bonferroni posttest (in black). B. eEF2K+/+, eEF2K-/-, eIF2αWT and eIF2αS51A MEFs were treated for 6h with indicated doses of NFR, 200 nM rapamycin, or 10 μg/ml TM, or for 30 min with 10 μg/ml CHX. 35S-methionine incorporation was measured by liquid scintillation counting. Data are shown as the percentage of translation compared to untreated cells. *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001 obtained using 2way ANOVA analysis of variance followed by Bonferroni posttest.",
    "ncbi_link": "eEF2K: 13631
EEF2K: 13631
eIF2α: 13665"
  },
  {
    "caption": "C Representative polysome profiles of eEF2K WT and KO MEF treated 6h with NFR or TM. Area under curve for Sub-polysomes (S) and Polysomes (P) used to calculate the P/S ratio were indicated (see also raw data provided). Bar graph represents ratio normalized to untreated cells. OD254 nm is optical density at 254 nm. Data showed mean ±s.e.m. of P/S ratio calculated from 3 independent experiments. P values were calculated using 1way ANOVA analysis of variance followed by Bonferroni posttest; *P value ≤ 0.05, ** P value ≤ 0.01.",
    "ncbi_link": "eEF2K: 13631"
  },
  {
    "caption": "D The ribosome half-transit time in MEFs eEF2K+/+ and eEF2K-/- was determined as described in Materials and Methods. Incorporation of 35S-Methionine into total protein within the PMS and PRS was obtained by linear regression analysis. Presented graphs are representative of two (CHX 1 μg/ml for 30 min and Starvation 30 min in PBS in eEF2K+/+ cells) to four (NFR 20μM for 6h in eEF2K+/+ and eEF2K-/- cells) independent experiments. Indicated values represent the x displacement measurement (in time) between the PMS line at 300sec and the PRS line (see also raw data provided). Histogram represents mean and s.e.m. of the ribosome half transit time from four independent experiments. P values were calculated using two tails unpaired Student's T-tests; *P value ≤ 0.05.",
    "ncbi_link": "eEF2K: 13631"
  },
  {
    "caption": "A MEF eEF2K WT, KO or KO reconstituted with human eEF2K (Flag-eEF2K) were analyzed for cell growth at indicated times. Fold change (means ± s.e.m of triplicate) of the cell number just before treatment are shown. Histogram shows percentage of growth inhibition after 72h of 10 μM NFR. P values are 1way ANOVA with Bonferroni posttest calculated from 3 independent experiments. *** P value ≤ 0.001.",
    "ncbi_link": "eEF2K: 29904
eEF2K: 13631"
  },
  {
    "caption": "B-F Dose response curves for cell viability after 48h NFR measured using MTS assay. Curves and bar graph for EC50 are mean ± s.e.m. of 3 independent experiments performed in triplicate. For curves, p values are 2way ANOVA analysis of variance. For bar graph, p values are two tails unpaired Student's T-tests (B, E), or 1way ANOVA with Bonferroni (C) or Dunnett's multiple comparison posttests (D and F). *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001. (B,C) eEF2K -/- MEFs show a decrease susceptibly to NFR compared to eEF2K +/+ controls (B) whereas eEF2K reconstitution restores NFR sensitivity (C).",
    "ncbi_link": "eEF2K: 29904
eEF2K: 13631"
  },
  {
    "caption": "B-F Dose response curves for cell viability after 48h NFR measured using MTS assay. Curves and bar graph for EC50 are mean ± s.e.m. of 3 independent experiments performed in triplicate. For curves, p values are 2way ANOVA analysis of variance. For bar graph, p values are two tails unpaired Student's T-tests (B, E), or 1way ANOVA with Bonferroni (C) or Dunnett's multiple comparison posttests (D and F). *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001. (D-F), HeLa (D), A549 (E) and MCF7 (F) clones with CRISPR-Cas9 generated eEF2K deficiency (CrEEF2K) show a decrease susceptibly to NFR compare to control cells (CrLuci).",
    "ncbi_link": "EEF2K: 29904
eEF2K: 29904"
  },
  {
    "caption": "A Tumor volumes of eEF2K -/- and eEF2K +/+ RasV12 engraft implanted subcutaneously in AGR129mice. Treatment with NFR or vehicle was initiated 6 days post-implantation. Data are mean of tumor volume ± s.e.m. (n = 8 per group). P values were calculated using 2way ANOVA followed by Bonferroni posttest comparing WT tumor with vehicle or NFR treatment and KO tumors with vehicle or NFR treatment; *P value ≤ 0.05, ** P value ≤ 0.01, *** P value ≤ 0.001. Experiment is representative of 2 performed in same conditions.",
    "ncbi_link": "eEF2K: 13631
Ras: 15461"
  },
  {
    "caption": "B Usp27x binds a mutant of Bim incapable of binding to anti-apoptotic Bcl-2-proteins. 293FT cells transfected with constructs encoding 3xFLAG-Usp27x and 3xHA-tagged BimEL (see A, 2µg each) or 3xHA-tagged BimEL∆∆(a mutant with two mutations in the BH3-domain, incapable of binding antiapoptotic Bcl-2proteins [50]) were immunoprecipitated from whole cell extracts using anti-HA-resin. Bim and Usp27x were detected with anti-HA- and anti-FLAG-antibodies as indicated; antiapoptotic proteins: Mcl-1, Bcl-XL, Bcl-2. The caspase-inhibitor Q-VD-OPh (QVD) was added to the cultures described in A and B to inhibit Bim-induced apoptosis. Western blots are representative of n=3 independent experiments.",
    "ncbi_link": "Bim: 12125
Usp27x: Q8CEG8///54651
Usp27x: 54651"
  },
  {
    "caption": "C Usp27x interacts with endogenous BimEL independently of its catalytic activity293FT cells either carrying 3xFlag-Usp27x (293FT-TetR-3xFlag-usp27x) or the catalytic inactive mutant 3xFlag-Usp27xC87A under the control of the Tet-repressor were treated for 24h with dox to induce expression of Usp27x or Usp27xC87A. In all conditions PMA (to induce Bim-ubiquitination, 16.2 nM), and Q-VD-OPh (to inhibit apoptosis, 10 µM, see Fig. 3) were added at the time of Usp27x-induction. MG132 (to prevent Bim-degradation, 40 µM) was added in all conditions 4h prior to cell lysis. 3xFlag tagged Usp27x or Usp27xC87A was immunoprecipitated from whole cell lysates using anti-Flag resin. Interaction with BimEL or β-TrCP was detected by Western blotting using anti-Bim or anti-β-TrCP antibodies. Western blots are representative of n≥3 independent experiments.",
    "ncbi_link": "TetR: 6276071
usp27x: 54651
Usp27x: 54651"
  },
  {
    "caption": "D Usp27x expression does not inhibit interaction of BimEL to β-TrCP293FT-TetR-3xFlag-Usp27x cells were transfected with pMIG-3xHA-BimEL in the presence of both PMA and QVD. At the same time dox (to induce 3xFlag-Usp27x) was added as indicated and 20h later cells were treated with MG132 [40µM] for additional 4h.Cells were lysed and 3xHA-BimEL was immunoprecipitated as described above. As a control HA-matrix was used without lysate to rule out any unspecific signal that might come from the immobilized anti HA-antibody (beads). Western blots show representative of n=2 independent experiments.",
    "ncbi_link": "Bim: 12125
TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "E Binding of Usp27x to BimEL can be blocked by the MEK-inhibitor UO126293FT-TetR-3xFlag-Usp27x cells (see C) were treated for 24h with dox to induce expression of Usp27x. In all conditions PMA [16.2 nM], and Q-VD-OPh [10 µM] were added at the time of Usp27x-induction. As a control, cells were pretreated with UO126 [10µM] for 30 minutes to block the PMA stimulated ERK pathway before the addition of dox plus PMA plus QVD. 3xFlag tagged Usp27x was immuno-precipitated from whole cell lysates using anti-Flag resin. Interaction with BimEL was detected by Western blotting using anti-Bim antibodies. As a control Flag-matrix (beads) was used alongside the IP under same conditions but without addition of protein lysates. Western blots are representative of n=4 independent experiments (see also Appendix Fig. S2B).",
    "ncbi_link": "TetR: 6276071
Usp27x: Q8CEG8///54651"
  },
  {
    "caption": "F Binding of Usp27xto BimEL does not require β-TrCP293FT-TetR-3xFlag-Usp27x cells were transfected with control siRNA (siCo3) or siRNA specific for β-TrCP. 48h later cells were stimulated with PMA plus dox plus QVD for additional 24h. After cell lysis, Flag-Usp27x was immuno-precipitated using anti-Flag-matrix, and BimEL and β-TrCP bound to Usp27x were identified by Western blotting. Blots are representative of n=2 independent experiments.",
    "ncbi_link": "β-TrCP: 8945
TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "G Usp27x binds specifically to BimEL293FT-TetR-3xFlag-Usp27x cells or 293FT-3xFlag-Usp27x cells with a specific deletion of the BimELprotein were treated with dox, PMA and QVD as in C. Cells were lysed, and lysates were subjected to anti-Flagimmunoprecipitation. 3xFlag-Usp27x was detected using anti-FLAG antibodies. Blots are representative of n=3 independent experiments.",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "A Usp27x inhibits the PMA-induced degradation of BimEL in 293FT cells. 293FT-TetR-3xFlagUsp27x or TetR-3xFlag-Usp27xC87A cells were treated with dox to induce 3xFlag-Usp27x or Usp27xC87A, or with PMA [16.2 nM] (to induce BimEL degradation), or with the combination of dox, PMA and QVD [10µM] (to inhibit apoptosis) as indicated for 24 h (left) or 48 h (right). Cell lysates were analysed by Western blotting. The blots are representative of n=4 similar experiments. See also Appendix Fig. S5B. * Probably modified form of wild-type 3xFlag-Usp27x (such as dimer, ubiquitinated Usp27x or a stable complex of Usp27x with another interacting partner); this form is only seen if high expression levels of catalytically active Usp27x are reached (see Appendix Fig. S5A where Usp27x was transfected into 293FT cells) or if wt Usp27x is enriched during immunoprecipitation.** Probably degradation product of 3xFlag-Usp27x. These forms of Usp27x were not seen in every experiment.",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "B 293FT-TetR-3xFlagUsp27x or TetR-3xFlag-Usp27xC87A cells treated as in A were analysed using conditions of higher resolution. A band very likely corresponding to phosphorylated BimEL is detectable. Similar results were obtained in n=2 separate experiments.",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "C Usp27x stabilizes expression of p-BimEL (Ser69) in Bim-degrading conditions without reducing β-TrCP levels293FT-TetR-3xFlagUsp27x were treated with dox, PMA [16.2 nM], UO126 [10µM] or QVD [10µM] as indicated for 24h, and levels of phosphorylated BimEL at serine69 were analysed by Western blotting using a phospho-Bim (Ser69) specific antibody. Scans are from the same membrane and exposure times. Similar results were obtained in n=2 separate experiments.",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "D UO126 reduces phosphorylation-associated shift of BimEL293FT-TetR-3xFlagUsp27x were treated for 24h with the indicated drug combinations and Bim was detected by Western blotting. UO126 was added 30 minutes prior other stimulation. Similar results were obtained in n=3 separate experiments (see Appendix Fig. S5D).",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "E Usp27x-expression reduces ubiquitination of Bim293FT-TetR-3xFlagUsp27x cells were transfected with a vector coding for 6His-ubiquitin (left) or GFP (right). After 24h cells were treated with PMA and QVD, and 3xFlag-Usp27x was induced by dox at the same time. After additional 20h cells were treated for 4h with MG132 (40 µM) to block proteasomal degradation of ubiquitinated proteins. Cells were lysed under denaturing conditions and His-ubiquitin-labelled proteins or proteins from only GFP expressing cells were purified by Ni2+-NTAaffinity chromatography. Ubiquitinated Bim (Bim-Ubn) was detected by Western blot using anti-Bim antibodies (left). Similar results were obtained in n=3 separate experiments (another experiment including a Coomassie stain is shown in Appendix Fig. S3E). *Indicates non-His-ubiquitinated BimEL that was bound unspecifically to the Ni2+-agarose beads",
    "ncbi_link": "TetR: 6276071
ubiquitin: 7311///6233///7316///7314
Usp27x: 54651"
  },
  {
    "caption": "A 293FT-TetR-3xFlag-Usp27x or 3xFlag-Usp27xC87A, a polyclonal derivative where the Bim-locus had been targeted by CRISPR/Cas9- and four single clones obtained by serial dilution from the polyclonal line were treated as indicated (PMA [16.2 nM], QVD [10 µM]). Apoptosis was measured after 24 h of treatment by staining for active caspase-3, followed by flow cytometric analysis. Data (means/SEM) are from n=14 (3xFlag-Usp27x line and 3xFlag-Usp27xBim2KO polyclonal line), n=5 (3xFlag-Usp27xC87A, and 3xFlag-Usp27xBim2KO clone #14), n=7 (3xFlag-Usp27xBim2KO clone #11) or n=4 (3xFlag-Usp27xBim2KO clone #4 and #7) separate experiments. P-values (t-test) for statistically significant differences are shown.",
    "ncbi_link": "Cas9: 
CRISPR: 
Bim: 10018
TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "B The same cells as in A (except Usp27xC87A mutant) were treated as in A and stained for active Bax. Data (means/SEM) are from n=8 (3xFlag-Usp27x line and 3xFlag-Usp27xBim2KO polyclonal line), n=5 (3xFlag-Usp27xBim2KO clone #11 and #14) or n=4 (3xFlag-Usp27xBim2KO clone #4 and #7) separate experiments. P-values (t-test) for statistically significant differences are shown. Expression levels of Bim, β-TrCP and Flag-Usp27x of the different cell lines are shown in Appendix Fig. S5E.",
    "ncbi_link": "Bim: 10018
Usp27x: 54651"
  },
  {
    "caption": "A Lines based on the human melanoma cell line 1205Lu (BRAF-V600E-positive) were made to carry GFP-Usp27x, GFP-Usp27xC87A or GFP-Usp22 under the control of a doxycycline (dox)-inducible promoter. GFP-Usp27x, GFP-Usp27xC87A or GFP-Usp22 were induced with dox for 24 or 48h. Levels of Bim were determined by Western blotting. The two left panels are from the same membrane and exposure times. Similar results were obtained in n=4 separate experiments (left) and n=3 experiments (right). See also Appendix Fig. S6A where 3xFlag-Usp22 is also shown to be unable to increase Bim levels.",
    "ncbi_link": "BRAF: 673
Usp22: 216825
Usp27x: 54651"
  },
  {
    "caption": "B A cell line derived from the BRAF-V600E-positive human melanoma line WM1158 was generated to carry inducible GFP-Usp27x. GFP-Usp27x was induced, and Bim was detected as in A. Similar results were obtained in n=3 separate experiments.",
    "ncbi_link": "BRAF: 673
Usp27x: 54651"
  },
  {
    "caption": "C Derivatives of the NSCLC cell line HCC827 (expressing constitutively active EGFR) were generated that only express the TetR-repressor or carrying in addition either GFP-Usp27x or GFP-Usp27xC87A. Cells were treated with dox for 72h. Bim was detected by Western blotting. Similar results were obtained in n=2 separate experiments. GFP-Usp27x, GFP-Usp27xC87A, or GFP-Usp22 expression (A-C) was detected using an antibody against GFP.",
    "ncbi_link": "EGFR: 1956
TetR: 6276071
Usp27x: Q8CEG8///54651"
  },
  {
    "caption": "D Caco2 cells carrying a dox inducible HA-BRAF-V600E [37] (left two lanes) or the same cells stably expressing 3xFlag-Usp27x were treated with dox for 48h to induce expression of HA-BRAF-V600E. Bim was detected by Western blotting. The amount of BimEL was quantified from the shown immunoblot using the expression levels of the uninduced control cells set to 100% (normalized to the tubulin signal for each condition). Similar results were obtained in n=3 separate experiments with varying induction times. See also Appendix Fig. S6D.",
    "ncbi_link": "BRAF: 673
Usp27x: 54651"
  },
  {
    "caption": "A Loss of endogenous Usp27x enhances destabilization of BimEL in response to BRAF-V600ECaco2 cells carrying inducible HA-BRAF-V600E were transfected with control siRNA (siCo3) or siRNA directed against Usp27x (combination of three siRNAs targeting Usp27xmRNA) for 24h prior to BRAF-V600E expression with dox for 2h (left) or 4h (right). BimEL was detected by Western blotting. Similar results were also observed in n=2 more experiments after 3h induction (not shown, see Appendix Fig. S6E for siRNA efficacy).",
    "ncbi_link": "BRAF: 673
Usp27x: 389856"
  },
  {
    "caption": "B 293FT cells deficient for Usp27x show enhanced destabilization of BimEL in response to PMA293FT wt cells or 293FT-Usp27xKO (clone 2/10, generated using CRISPR-Cas-9) were treated with PMA [16.2 nM] for 16h or 24h to induce BimEL degradation. Western blots show protein levels of n=3 independently performed experiments (similar results were obtained in one more experiment, not shown). See Appendix Fig. S6G for verification of the Usp27xKO cell line by DNA sequence analysis.",
    "ncbi_link": "Cas-9: 
CRISPR: 
Usp27x: 389856"
  },
  {
    "caption": "A 293FT-TetR-3xFlagUsp27x cells were treated with PMA [16.2 nM] plus QVD [10 µM] and 3xFlag-Usp27x was induced by dox at the same time for 24h followed by addition of cycloheximide (CHX). Cells were harvested at the indicated time points, and levels of BimEL were determined by Western blotting. Similar results were obtained in n=3 separate experiments. Cut membranes shown were from one membrane with same exposure time. For each condition BimEL-levels were quantified and normalized to the tubulin-signal. Percent BimEL gives the expression relative to the starting point.",
    "ncbi_link": "TetR: 6276071
Usp27x: 54651"
  },
  {
    "caption": "B 1205Lu melanoma cells carrying dox-inducible GFP-Usp27x were treated with dox for 24h. Cycloheximide (CHX, 1µg/ml) was then added. Cells were harvested at the indicated time points, and levels of BimEL were determined by Western blotting. GFP-Usp27x was detected with anti-GFP-antibodies. Similar results were obtained in n=3 separate experiments. A second experiment is shown in the right panel also including 1205Lu melanoma carrying dox-inducible GFP-Usp27xC87A mutant. For each condition BimEL-levels were quantified and normalized to the tubulin-signal. Percent BimEL gives the expression relative to the starting point set to 100%. The starting point for the non-Usp27x/C87A inducing cells (-dox) is shown in lane 1 for experiment one and two (-dox, - CHX). Cut membranes shown were from one membrane with same exposure time. Same results were obtained for WM1158 melanoma cells (data not shown).",
    "ncbi_link": "Usp27x: 54651"
  },
  {
    "caption": "C HCC827 cells were induced to express GFP-Usp27x with dox as indicated. 24h later cycloheximide (CHX, 1µg/ml) was added for the indicated time. BimEL was detected after the indicated times of treatment by Western blotting. For each condition BimEL-levels were quantified and normalized to the tubulin-signal. Percent BimEL gives the expression relative to the starting point. Similar results were obtained in n=2 separate experiments. Cut membranes shown were from one membrane with same exposure time.",
    "ncbi_link": "Usp27x: 54651"
  },
  {
    "caption": "A 1205Lu melanoma cells carrying dox-inducible GFP, GFP-Usp27x or GFP-Usp27xC87A were treated with doxycycline (dox) as indicated. After 48 hUO126 (10µM) was added for another 48 h. Apoptosis was measured by staining for active caspase-3, followed by flow cytometric analysis. Data (means/SEM) are from n=3 (GFP) or from n≥6 separate experiments (GFP-Usp27x and GFP-Usp27xC87A). P-values (t-test) for statistically significant differences are shown. N.s., p>0.05. The addition of QVD inhibited cells from active Caspase-3 positive staining (not shown). A stain for active Bax is shown in Appendix Fig. S7B.",
    "ncbi_link": "Usp27x: 54651"
  },
  {
    "caption": "B HCC827 NSCLC cells carrying dox-inducible GFP-Usp27xC87A, GFP-Usp27x, or two separate lines established from these GFP-Usp27x-cells where the Bim-locus had been targeted for deletion using CRISPR/Cas9 (Bim-KO), were treated with combinations of dox and the EGFR-inhibitor gefitinib as indicated. Apoptosis was measured after 72h of treatment by staining for active caspase-3, followed by flow cytometric analysis. Data (means/SEM) are from n=≥15 (maternal GFP-Usp27x line) or from n≥5 (for Bim1KO) or from n≥6 (for Bim2KO), or n=4 (for GFP-Usp27xC87A) separate experiments. P-values (t-test) for statistically significant differences are shown. Again, the addition of QVD inhibited cells from active Caspase-3 positive staining (not shown). The inset shows Bim-knock-out-efficiency (n=2).",
    "ncbi_link": "Cas9: 
CRISPR: 
Bim: 10018
EGFR: 1956
Usp27x: 54651"
  },
  {
    "caption": "Figure 8 Loss of Usp27xreduces gefitinib-induced apoptosis in HCC827 NSCLCHCC827 NSCLC cells and two separate polyclonal lines established from these cells where the Usp27x-locus had been targeted for deletion using CRISPR/Cas9 with two different guide RNA against Usp27x (Usp27xKO-1 and Usp27xKO-4), were treated with gefitinib [10µM] for 48h. Apoptosis was measured by staining for active caspase-3 (A) or by staining for activated Bax (antibody: 6A7 clone) followed by flow cytometric analysis. Data shown in A, B (means/SEM) are from n=4 separate experiments. P-values (t-test) for statistically significant differences are shown.",
    "ncbi_link": "Cas9: 
CRISPR: 
Usp27x: 389856"
  },
  {
    "caption": "D. Representative images of the intestine  of Casp8WT and Casp8ECko mice, with mild and severe hemorrhages  at a late disease stage.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "E-F. Representative images of H&E staining  (E) and quantification of intestinal pathology  (F) of the small intestine at an early disease stage in  Casp8WT and Casp8ECko mice  (enteropathy score; n= 6 WT, 6 ECko; two tailed unpaired Student's t-test). Scale bars: 100µm; insets 50µm. Data information: Data shown as mean ± SEM. **P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "G-H. Quantification of intestinal pathology (enteropathy score, G; n= 8 WT, 7 ECko; two tailed unpaired Student's t-test) and hemorrhages  into the mucosa (H; n= 4 WT, 5  ECko; two tailed unpaired Student's t-test) at a late disease stage in Casp8WT and Casp8ECko mice. Data information: Data shown as mean ± SEM. **P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "I. Overview of H&E stained  swiss roll preparations of Casp8WT and Casp8ECko mice. Scale bars: 2mm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "J. Representative images of H&E staining  of the small intestine of  Casp8WT (j') and  Casp8ECko mice  with mild (j'') and more severely (j''') affected areas at a late disease stage (white arrows point to hemorrhages, asterisk points to   focal erosion of the epithelium). Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "A-B. QPCR analysis of genes associated to immune and bacterial response (A), vessel  permeability and EC activation (B) in small intestine  lysates at a late disease timepoint in Casp8WT and  Casp8ECko mice (n= 4 WT, 3-4 ECko, biological replicates, multiple t-test with Holm-Sidak method). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Graphs revealing that significantly upregulated cytokines in the proteome  profiler in Casp8ECko mice  are associated to the complement cascade (C) (n= 4 WT, 4 ECko, multiple t-test with Holm- Sidak method). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Graphs revealing that significantly upregulated cytokines in the proteome  profiler in Casp8ECko mice  are associated to the mucosal  healing (D) (n= 4 WT, 4 ECko, multiple t-test with Holm- Sidak method). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Representative images (E; area between dotted lines shows crypts) of Ki67 staining  in small intestine at an early disease stage in  Casp8WT and  Casp8ECko mice  (n= 5 WT, 6  ECko Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "quantification (F) of Ki67 staining  in  small intestine at an early disease stage in Casp8WT and Casp8ECko mice  (n= 5 WT, 6 ECko two tailed unpaired Student's t-test). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "G. QPCR  analysis of the proliferation  markers Ki67  and  c-myc in ileal lysates from late disease stage  Casp8WT and Casp8ECko mice  (n= 4 WT, 3-4ECko, two-way ANOVA with Sidak method). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001.",
    "ncbi_link": "Casp8: 12370
Ki67: 17345
c-myc: 17869"
  },
  {
    "caption": "H. Representative images of E-Cadherin staining, showing intact epithelial    barrier integrity in Casp8ECko mice  in healthy areas (h'), and disrupted barrier integrity in intestinal  lesions (h'') at late disease stages compared to Casp8WT mice  (n= 4 WT, 4 ECko). Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "I. Representative pictures of CD45  and NIMPR14  staining  at late disease stages (n= 5 WT, 5 ECko), showing accumulation of CD45+ and  NIMPR14+ cells (black arrowheads) in Casp8ECko intestine  at sites of impaired epithelial  barrier integrity and tissue necrosis   (red asterisks). Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "J. Representative images of CD4, F4/80  and MPO stainings in  small intestines at a late disease stage showing accumulation of these cells at the crypt  base in Casp8ECko mice  (arrowheads) (n= 4 WT, 4  ECko). Scale bars: 50µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "A. Representative pictures showing Peyer´s Patches in Casp8WT mice, and different severities of hemorrhage  formation in Casp8ECko mice  at an early disease stage. Scale bars: 1mm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Quantification of lymphatic vessel density (B) in Peyer's Patches in Casp8WT and Casp8ECko mice  at an early disease stage (n = 9 WT, 7-10 ECko  Peyer's Patches  are pooled from 4-6 mice  per genotype; one-way ANOVA with tukey's multiple comparison). Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "representative pictures of CD31  (pan EC) and  Lyve1 (lymphatic) staining (C) in Peyer's Patches  in Casp8WT and Casp8ECko mice  at an early disease stage (n = 9 WT, 7-10  ECko Peyer's Patches are pooled from 4-6 mice  per genotype Scale bars: 200µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "D-F. Representative images (D) and quantifications (E, F) of stainings   for CD31, Lyve1  and DAPI (nuclei) in  small intestinal wholemounts at an early disease stage (blue arrowheads point to defective lacteals, white arrowheads indicate edema) in Casp8ECko mice  (E; n= 7 WT, 6 ECko. F; n= 7 WT, 10 ECko; two tailed unpaired Student's t-test). Scale bars: 100µm. Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "G. Representative images of small intestine  sections of mice  injected with a 70kDa fluorescently labeled dextran  and stained  for CD31  at an early disease stage. White arrowheads point to extravasated dextran  in Casp8ECko mice  (n= 5 WT, 5 ECko). Scale bars: 50µm. H. Quantification of extravasated dextran  in small intestine  and brain  lysates in Casp8WT and  Casp8ECko mice  at an early disease stage (n= 4 WT, 4-5 ECko; two-way ANOVA with tukey's multiple comparison). RFU: relative fluorescent units. Data information: Data shown as mean ± SEM. * P <0.05, ** P <0.01, *** P <0.001, **** P <0.0001, ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "I. Representative images of CD31  and VE-Cadherin staining  in intestinal  wholemounts at an early disease stage (n= 5 WT, 5 ECko) in  Casp8WT and  Casp8ECko mice  (red arrowheads point to  VE-Cadherin  'empty' vessel patches). Scale bars: 25µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "A-B. Representative images (A) and quantification (B) of CD31, TUNEL and DAPI staining in small intestine sections of Casp8WT and Casp8ECko mice  at an early disease stage (red dotted lines: epithelium; white dotted lines: endothelium) in (n= 5 WT, 5  ECko, multiple t-tests with Holm-Sidak method). Scale bars: 100µm. Data information: All data is shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "D-E. Graphs showing survival  and relative weight  of Casp8WT/MLKLko and  Casp8ECko/MLKLko mice  upon tamoxifen  treatment. (D; n= 5-8 WT/ MLKLko, 5-8 ECko/MLKLko; Log-Rank test, E; n= 7 WT, 8  ECko; two tailed unpaired Student's t-test).",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "F. Representative pictures of intestines  of Casp8WT/MLKLko and Casp8ECko/MLKLko mice  at 30 days after tamoxifen  treatment (n= 8 WT, 8 ECko).",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "G. Representative images of stainings  for CD31, Lyve1  and DAPI  in  small intestinal wholemounts from Casp8WT/MLKLko and Casp8ECko/MLKLko mice  at 30 days after tamoxifen  treatment. Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "H-K. Quantification of vessel area (H, I) and lacteal  length (J, K) at two different timepoints  after tamoxifen  treatment in Casp8WT/MLKLko and Casp8ECko/MLKLko mice  (n= 4-6 WT/MLKLko, 5  ECko/MLKLko; two tailed unpaired Student's t-test). Data information: All data is shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "L. Graph showing quantification of extravasated  70kDa Dextran  from small intestine  tissue of Casp8WT/MLKLko and Casp8ECko/MLKLko mice  at 30 days after tamoxifen  treatment (n= 7 WT/MLKLko, 6 ECko/MLKLko; two tailed unpaired Student's t-test). Data information: All data is shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "M-N. Representative pictures (M) and quantification (N) of lymphatic vessel density in  Peyer's Patches of  Casp8WT/MLKLko and Casp8ECko/MLKLko mice  at 140 days after tamoxifen  treatment (n = 8 WT, 7 ECko Peyer's Patches are pooled from 4 mice  per genotype; two-tailed unpaired students t-test). Scale bars: 200µm. Data information: All data is shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "O. Representative pictures of H&E stainings  of  small intestine  tissue of Casp8WT/MLKLko and Casp8ECko/MLKLko mice  (n= 4-6 WT, 4-5  ECko). Scale bars: 100µm. P-Q. Quantification of intestinal pathology  in Casp8WT/MLKLko and Casp8ECko/MLKLko mice  at two different timepoints  after tamoxifen  treatment (enteropathy score; n=4-6 WT/MLKLko, 5 ECko/MLKLko; two tailed unpaired Student's t-test). Data information: All data is shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "A. Representative pictures of TUNEL staining together with CD31  and  Lyve-1  in  Peyer's Patches  of Casp8WT and Casp8ECko mice. TUNEL+ LECs, but not  BECs could already be seen in non-hemorrhagic Peyer's Patches  (a'), and further accumulated in hemorrhagic Peyer's Patches (a''). White dotted areas outline location of the lymphatic plexus. White arrowheads point to TUNEL+ LECs  (note that necroptotic LECs only weakly express Lyve-1). Scale bars: 50µm, insets: 10µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "C. Survival (n= 5 WT, 6 BECko; Log-Rank test) of Casp8WT and Casp8ECko mice  upon tamoxifen  treatment.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "D. Representative pictures of intestines  of Casp8WT and Casp8BECko mice.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Representative pictures of H&E staining of small intestine  of Casp8WT and Casp8BECko mice (E),  enteropathy score (F; n= 5 WT, 6 ECko, two tailed unpaired Student's t-test) Scale bars: 100µm, insets: 50µm. Data information: Data shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Representative images of stainings  for CD31, Lyve1  and DAPI  in small intestinal  wholemounts (H) and quantification of vessel density (I) in  Casp8BECko compared to Casp8WT mice (I; n= 5 WT, 6 BECko; two tailed unpaired Student's t-test, Scale bars: 100µm. Data information: Data shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "quantification of lacteal  length (J) in  Casp8BECko compared to Casp8WT mice  ; n= 5 WT, 5 BECko; two tailed unpaired Student's t-test with Welch's correction). Data information: Data shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "K-L. Representative pictures (K) and quantification (L) of lymphatic vessel density  Peyer's Patches in  Casp8WT and Casp8BECko mice  (n = 10 WT, 11 BECko Peyer's Patches  from 5-6 mice per genotype; two tailed unpaired Student's t-test). Scale bars: 200µm. Data information: Data shown as mean ± SEM. ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "B. Survival  graph after intravenous TNF-α injection of Casp8WT vs. Casp8ECko mice  within the first 24h (n=11 WT, 11 ECko; Log-Rank test).",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "C. Representative images of the small intestines 24h after  TNF-α injection in Casp8WT and Casp8ECko mice  (blue arrowheads point to Peyer's Patches).",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "D-E. Representative pictures of Peyer's Patches (D) and quantification of lymphatic vessel density (E) in Casp8WT, Casp8ECko and Casp8ECko/MLKLko mice  injected with TNF-α (n=7 WT, 5 ECko, 15 ECko/MLKLko. Peyer's Patches  are pooled from 3-5 mice  per genotype). Scale bars: 200µm. Data information: All data is shown as mean ± SEM. * P<0.05, *** P <0.001, **** P <0.0001; ns: not significant.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "F. Representative pictures of TUNEL staining  together with CD31  and Lyve-1 in  Peyer's Patches of Casp8WT, Casp8ECko and Casp8ECko/MLKLko mice injected with TNF-α. TUNEL+ LECs, but not BECs  could already be seen in Casp8ECko, but neither in Casp8WT nor in Casp8ECko/MLKLko mice. White dotted areas outline location of the lymphatic plexus. Yellow arrowheads point to TUNEL+ECs). Scale bars: 50µm.",
    "ncbi_link": "Casp8: 12370
MLKL: 74568"
  },
  {
    "caption": "H. Survival  graph of Casp8WT and Casp8ECko mice  after Enbrel® treatment (n=7 WT, 5  ECko +  IgG, 8 ECko + Enbrel; Log-Rank test).",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Representative images of small intestines (I) of  Casp8ECko mice  after Enbrel® treatment Scale bars: 100µm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "Representative images of H&E staining  (J) with histopathological scoring (K) of Casp8WT and Casp8ECko mice   after Enbrel® treatment (n=6 WT, 4 ECko +  IgG; 8  ECko + Enbrel (from which 3 mice  were diseased, 5 mice  healthy); one-way ANOVA with tukey's multiple comparison). Scale bars: 100µm. Data information: All data is shown as mean ± SEM. * P<0.05, *** P <0.001, **** P <0.0001; ns: not significant.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "analysis of the most prominent bacterial phyla (B; n= 4 Control, 6-8 Antibiotics; multiple t-tests with Holm-Sidak method) by qPCR analysis, In B, the cycle number of 16S rDNA expression  compared to the total number of cycles is shown. Data information: Data shown as mean ± SEM. ** P <0.01, *** P <0.001, **** P <0.0001; ns: not significant. Scale bars: 100μm.",
    "ncbi_link": "16S rDNA: "
  },
  {
    "caption": "E. Representative images of the gut  of  Casp8WT and Casp8ECko mice  with antibiotic  treatment 30 days after tamoxifen.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "F-H. Representative images of H&E staining  (F), quantification of intestinal pathology  (G) and mucosal hemorrhages  (H) in  Casp8WT and Casp8ECko mice treated with antibiotics  compared to untreated Casp8ECko mice (G; n= 6 WT, 4 ECko+ antibiotics, 5  ECko; one-way ANOVA with tukey's multiple comparison, H; n= 6 WT, 4 ECko+ antibiotics, 4 ECko; one-way ANOVA with tukey's multiple comparison). Data information: Data shown as mean ± SEM. ** P <0.01, *** P <0.001, **** P <0.0001; ns: not significant. Scale bars: 100μm.",
    "ncbi_link": "Casp8: 12370"
  },
  {
    "caption": "A summary bar graph showing the quantitative real-time PCR data for TMEM16A, TMEM16B, and BEST1 with cDNA samples prepared from the mHb and hippocampus of adult mouse brains (N=3, n=3 each, unpaired Student t-test, data are presented as mean values ± s.e.m.).",
    "ncbi_link": "TMEM16A: 101772
TMEM16B: 243634
BEST1: 24115"
  },
  {
    "caption": "RNAscope ISH showed an apparent expression of TMEM16A mRNA co-localized with ChAT and Tac1 signals in the mHb compared to the ones in lHb. Enlarged images showed that signals of TMEM16A and Tac1 in the dorsal mHb or ChAT in the ventral mHb reside together at the single cell level.",
    "ncbi_link": "TMEM16A: 101772
ChAT: 12647
Tac1: 21333"
  },
  {
    "caption": "Immunohistochemical staining of 40-µm coronal brain sections with an anti-TMEM16A antibody. The TMEM16A signals in the mHb of TMEM16A cKO mice were compared to the ones of littermate controls. TMEM16A colocalized with the cholinergic marker ChAT in the mHb. The specific deletion of TMEM16A in the mHb is evident.",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Representative traces demonstrating the spontaneous activity of the mHb neurons in a cell-attached mode from TMEM16A cKO mice compared to the one from littermate controls. D. A summary bar graph showing the frequencies of spontaneous firing of the mHb neurons in TMEM16A cKO (4 mice) and littermate controls (The numbers inside each bar indicate the numbers of recorded cells from 4 mice each, paired Student t-test, data are presented as mean values ± s.e.m.).",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Representative averaged traces of sAPs of the mHb neurons with the pipette solution (40 mM Cl- and 0.5 mM EGTA) from TMEM16A cKO mice and littermate controls.",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Summary bar graphs showing the frequency, half-width, and AHP slope of the sAPs of mHb neurons from TMEM16A cKO mice and littermate controls (The numbers inside each bar indicate the numbers of recorded cells, unpaired Student t-test, data are presented as mean values ± s.e.m.).",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Immunohistochemical images of the IPN region from control and TMEM16A cKO mice. The c-Fos signal was greatly reduced in TMEM16A cKO mice. Scale bar = 200 μm.",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "A summary bar graph showing reduced c-Fos expression in the IPN in TMEM16A cKO mice. (NCTL=7 (n=42), NcKO=6 (n=36), unpaired Student t-test, data are presented as mean values ± s.e.m.).",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Representative traces of sEPSCs of neurons in the medial part of the IPN showing a reduced frequency in TMEM16A cKO mice compared to that of littermate controls.",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Summary bar graphs of the frequency and amplitude of the sEPSCs of IPN neurons in TMEM16A cKO (cKO) mice and littermate controls (CTL). Data are presented as mean values ± s.e.m. (paired Student t-test). The numbers inside each bar indicate the numbers of recorded cells.",
    "ncbi_link": "TMEM16A: 101772"
  },
  {
    "caption": "Representative traces showing that the spontaneous firing of mHb neurons from ChAT(+)-cre::hM4D(Gi) mice were reduced when CNO (10 μM) was applied in the ACSF.",
    "ncbi_link": "hM4: 1132
cre: 2777477"
  },
  {
    "caption": "A summary bar graph showing the reduction of normalized frequencies of spontaneous firing of the mHb neurons transfected with AAV-hM4Di-mCherry before and during CNO treatment (The numbers inside each bar indicate the numbers of recorded cells).",
    "ncbi_link": "mCherry: 
hM4: 1132"
  },
  {
    "caption": "In the EPM task, the time spent in the open arms of CNO-treated ChAT(+)-cre::hM4D(Gi) mice was significantly decreased compared to that of the PBS-treated controls (CTL). (nCTL=6, ncKO=9, unpaired Student t-test). E. In the LDB task, the time spent in the light zone by CNO-treated ChAT(+)-cre::hM4D(Gi) mice was significantly decreased compared to that spent by the PBS-treated control mice. (nCTL=6, ncKO=9, unpaired Student t-test). F. In the PA task, the entry latency of CNO-treated mice was significantly decreased compared to that of the CTL group. (nCTL=6, ncKO=9, unpaired Student t-test). G. Nestlet shredding behaviors of the CNO-treated ChAT(+)-cre::hM4D(Gi) mice were also decreased. (nCTL=6, ncKO=9, unpaired Student t-test;).",
    "ncbi_link": "ChAT: 12647
hM4: 1132
cre: 2777477"
  },
  {
    "caption": "In the 3-chamber test, the subject mouse of the PBS-treated mice and the CNO-treated mice explored freely the three test chambers. The time spent in each chamber during two sessions was measured. The CNO-treated ChAT(+)-cre::hM4D(Gi) mice exhibited a decreased interest for a stranger mouse (S1) against objects (O) compared to the PBS-treated group (left two panels) (nCTL=6, ncKO=9, unpaired Student t-test). I. When CNO-treated ChAT(+)-cre::hM4D(Gi) mice were exposed to a new stranger mouse (S2) against the familiar S1 mouse, they also showed a decreased interest for the S2 mouse compared to the PBS-treated control group (right two panels). The preference index showed decreased sociability of the CNO-treated group in both sessions (nCTL=6, ncKO=9, unpaired Student t-test;).",
    "ncbi_link": "ChAT: 12647
hM4: 1132
cre: 2777477"
  },
  {
    "caption": "MCF7, MCF7/ADR and MCF7/IR, MDA-MB-231 and MDA-MB-231/ADR cells were harvested and mRNA levels of BRD7 were determined by real-time PCR (n=3). Values are mean ± SEM and Error bars indicate SEM.",
    "ncbi_link": "BRD7: 29117"
  },
  {
    "caption": "Silver staining of the BRD7 complex separated by SDS-PAGE. HEK293T cells stably expressing SFB-tagged BRD7 were used for tandem affinity purification (TAP) of protein complexes. BRD7-interacting proteins, including PARP1 and PIK3R2, are indicated.",
    "ncbi_link": "BRD7: 29117"
  },
  {
    "caption": "HEK293T cells transiently transfected with Flag-PARP1 and Myc-BRD7 for 24 h were lysed with RIPA buffer. Followed by immunoprecipitation (IP) using antibodies to Myc (C) conjugated to agarose followed by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "Flag: 
Myc: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HEK293T cells transiently transfected with Flag-PARP1 and Myc-BRD7 for 24 h were lysed with RIPA buffer. Followed by immunoprecipitation (IP) using antibodies to Flag (D) conjugated to agarose followed by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "Flag: 
Myc: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa and 293T cells transfected with Myc-BRD7 plasmid for 24 h were lysed with RIPA buffer. Lysates were then immunoprecipitated using anti-Myc agarose and immunoblotted using the indicated antibodies. Ribosylation levels of exogenous BRD7 were detected using anti-PAR antibody (n=3).",
    "ncbi_link": "Myc: 
BRD7: 29117"
  },
  {
    "caption": "HeLa cells transfected with Myc-BRD7 plasmid. After 24 hours, cells were treated with either CPT (1 μM) or ADR (5 μM) combined with MG132 (10 μM) for indicated times. Cellular lysates were immunoprecipitated using anti-Myc agarose and immunoblotted using the indicated antibodies (n=3).",
    "ncbi_link": "Myc: 
BRD7: 29117"
  },
  {
    "caption": "HeLa PARP1 wild-type and PARP1 knockout cells were transfected with Myc-BRD7 for 24 h, lysates were subjected to immunoprecipitation using anti-Myc agarose and analysed by Western blot (n=3).",
    "ncbi_link": "Myc: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa were transfected with BRD7 wild-type and various BRD7 mutant plasmids for 24 h, lysed with RIPA, followed by anti-Myc IP and Western blot with indicated antibody (n=3).",
    "ncbi_link": "BRD7: 29117"
  },
  {
    "caption": "HeLa cells were transfected with Flag-PARP1 and Myc-BRD7 for 24 h, then treated with MG132 (10 μM) for additional 4 h, and proteins were detected by Western blot with indicated antibodies (n=3).",
    "ncbi_link": "Flag: 
Myc: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa cells were transfected with either scrambled or PARP1 siRNAs for 48 h, protein levels were detected by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "Expression of BRD7, p21 and PARP1 measured in PARP1 wild-type and knockout HeLa cells using PARP1 sgRNA by Western blot (n=3).",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "Wild-type and PARP1 knockout HeLa cells were incubated with 10 μg/ml cycloheximide (CHX) for the indicated times. Lysates were harvested and analysed by Western blot. Quantification of BRD7 protein are shown in F (n=3) and results represent mean ± SEM. Error bars indicate SEM. Relative amounts normalized to the BRD7 protein level at 0 h of Control or sgPARP1 cells, respectively.",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "PARP1 wild-type and knockout HeLa cells were transfected with HA-ubiquitin for 24 h, and MG132 (10 μM) was added for an additional 4 h, cells were lysed with RIPA buffer; followed by anti-BRD7 IP and analysed by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "HA: 
PARP1: 142"
  },
  {
    "caption": "SFB-BRD7 stably overexpressing HeLa cells transfected with scramble or PARP1 siRNA for 24 h were transfected with vector or HA-ubiquitin (Lys48 or Lys63 only) for 24 h, and MG132 (10 μM) was added for an additional 4 h, lysed with RIPA, subjected to IP using S tag beads followed by Western blot (n=3).",
    "ncbi_link": "HA: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa cells were co-transfected either wild-type or BRD7 mutant with Flag-PARP1 for 24 h and analysed by Western blot (n=3).",
    "ncbi_link": "Flag: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa cells were co-transfected with either wild-type or BRD7 mutant plus HA-ubiquitin for 24 h, and MG132 (10 μM) was added for an additional 4 h and lysed with RIPA buffer, followed by anti-Myc agarose IP and analysed by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "HA: 
BRD7: 29117"
  },
  {
    "caption": "HeLa and MDA-MB-231 cells were transfected with either scrambled or RNF146 siRNAs (48 h). Protein levels were detected by Western blot. PTEN, which is a known RNF146-interacting protein, was included as a positive control (n=3).",
    "ncbi_link": "RNF146: 81847"
  },
  {
    "caption": "HeLa cells were transfected with either scrambled or RNF146 siRNAs for 48 h, followed by incubation with 10 μg/ml cycloheximide (CHX) for the indicated periods of time. Lysates were harvested and analysed by Western blot (n=3). Quantification of BRD7 protein levels from B, n=3. Error bars indicate SEM. Relative amounts normalized to the BRD7 protein level at 0 h.",
    "ncbi_link": "RNF146: 81847"
  },
  {
    "caption": "Control and RNF146 stably overexpressing HeLa cells were transfected with Myc-BRD7-WT for 24 h, followed by incubation with 10 μg/ml cycloheximide (CHX) for indicated periods of time. Lysates were subjected to Western blot analysis (n=3). Quantification of BRD7 protein levels from D, n=3. Error bars indicate SEM. Relative amounts normalized to the BRD7 protein level at 0 h.",
    "ncbi_link": "Myc: 
BRD7: 29117
RNF146: 81847"
  },
  {
    "caption": "HeLa cells transfected with either RNF146 or control siRNA for 24 h followed by transfection of HA-ubiquitin for another 24 h; MG132 (10 μM) was added for 4 h and lysed with RIPA, followed by anti-BRD7 IP and analysed by Western blot with the indicated antibodies (n=3).",
    "ncbi_link": "HA: 
RNF146: 81847"
  },
  {
    "caption": "HeLa cells stably expressing RNF146 were transfected with HA-ubiquitin for 24 h; MG132 (10 μM) was added for an additional 4 h, followed by anti-BRD7 IP and Western blot (n=3).",
    "ncbi_link": "HA: 
RNF146: 81847"
  },
  {
    "caption": "HeLa cells with wild-type or PARP1 knockout were transfected with Myc-BRD7-WT for 24 h, their lysates were subjected to IP using anti-Myc agarose and analysed by Western blot with indicated antibodies (n=3).",
    "ncbi_link": "Myc: 
BRD7: 29117
PARP1: 142"
  },
  {
    "caption": "HeLa cells stably expressing Flag-RNF146 were transfected with either Myc-BRD7-WT or Myc-BRD7-mutant for 24 h, lysates were subjected to IP using anti-Flag agarose and analysed by Western blot with indicated antibodies (n=3).",
    "ncbi_link": "Flag: 
Myc: 
BRD7: 29117
RNF146: 81847"
  },
  {
    "caption": "MDA-MB-231 cells were transfected twice with BRD7 siRNAs, and these cells were subjected to CCK8 assay after treatment with Olaparib (10 μM) combined with either ADR (0.5 μM) or VP16 (10 μM) for 72 h (n=3). Results represent mean ± SEM of three experiments and Error bars indicate SEM. N.S., not significant; **P < 0.01, Student's t test.",
    "ncbi_link": "BRD7: 29117"
  },
  {
    "caption": "Resistance of BRD7-depleted cells to Olaparib was reversed by the expression of wild-type BRD7 but not mutant BRD7. shRNA-resistant BRD7 wild-type and BRD7 mutant plasmids were transduced into BRD7-depleted MDA-MB-231 cells, and cell viability was determined as indicated above (n=3). Results represent mean ± SEM of three experiments and Error bars indicate SEM. N.S., not significant; **P < 0.01, Student's t test.",
    "ncbi_link": "BRD7: 29117"
  },
  {
    "caption": "A -C. Drug-resistant ABL1-T315I rescues dasatinib- and imatinib-induced cytotoxicity. Western blot analysis of (A) transient and (B) tetracycline-inducible overexpression of ABL1-T315I in H1915 cells treated with dasatinib or imatinib.",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "C. CFA with dasatinib or imatinib for H1915 cells with or without tetracycline-inducible expression of ABL1-T315I. Error bars represent mean ±S.E.M., n=9, *P<0.001 by two-tailed unpaired Student's t-test (control, DMSO vs dasatinib P=4.3×10-12 vs imatinib P=6×10-6; dasatinib, control vs tetracycline, P=9×10-7; imatinib, control vs tetracycline P=9.7×10-5).",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "D-F. Knockdown of mutated ABL1 reduces viability of lung cancer cells. Top, western blot analysis of ABL1 knockdown in (D) Beas-2B, (E) H1915 and (F) H2110 cells upon transfection with three ABL1 siRNAs, negative control (scrambled) and CyclophilinB positive control. Bottom, MTT assay showing viability of (D) Beas-2B, (E) H1915 and (F) H2110 cells in response to ABL1 knockdown. Error bars represent mean ±S.E.M, n=9, *P<0.005, **P<0.001 by two-tailed unpaired Student's t-test (Beas-2B, scrambled vs siABL1-3 P=0.002; H1915, scrambled vs siABL1-1 P=0.004, vs siABL1-2 P=0.001, vs siABL1-3 P=0.002; H2110 scrambled vs siABL1-1 P=5×10-6, vs siABL1-2 P=2×10-5, vs siABL1-3 P=4.2×10-6).",
    "ncbi_link": "ABL1: 25
CyclophilinB: 5479"
  },
  {
    "caption": "A-C. Average tumor volumes of xenografts derived from H1915 (A), H650 (B) and (C) H1915 cell line with doxycycline inducible ABL1 gate-keeper mutation (H1915-ABL1T315I) in mice treated with either vehicle or imatinib (100mg/kg). Error bars represent ±S.D., n=6-10 mice per group, *P=0.0016 by Mann-Whitney U test.",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "A and C. Root mean square deviation (RMSD) analysis of the movement of (A) αC-helix and (C) DFG motif in the active and inactive conformation of ABL1 kinase with R351W mutation (orange) compared to the wild type (WT) kinase (black). B and D. Time-lapse images show movement within the αC-helix (B) and DFG motif (D) of the inactive structure of the WT (black outline) and R351W (orange outline) constructs.",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "E. left, western blot analysis of transient overexpression of wild type ABL1 (WT) and ABL1-R351W, compared to empty vector control (EV) in HEK293T cells. Right, quantification of p-CRKL signal based on densitometry analysis of blots from 6 independent experiments. Error bars represent ±S.D., n=6, *P=0.0004 by two-tailed unpaired Student's t-test.",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "F. Overexpression of mutant ABL1 constructs with mutations identified in selected primary lung tumors (Ding et al, 2008) in H157 cells. Values indicate quantified band intensity for p-CRKL, relative to α-tubulin and HA-tagged ABL1.",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "A. Immunofluorescence imaging of endogenous ABL1 in the panel of NSCLC cell lines; scale bars=20 μm. B and C Quantification of nuclear versus cytoplasmic localization of (B) endogenous ABL1 in NSCLC cell lines and (C) tetracycline-inducible expression of ABL1-WT, ABL1-R351W and ABL1-G340L in Beas-2B cells. Error bars represent ±S.D., n=6-10 images, *P<0.005 by two-tailed unpaired Student's t-test (Beas-2B vs H1915 P=6.6×10-5, vs H2110 P=0.0001; WT vs R351W P=0.003, vs G340L P=0.002).",
    "ncbi_link": "ABL1: 25"
  },
  {
    "caption": "(F) Single tube qPCR experiments showing the down-regulation of the synaptic genes NLGN3, SLC6A, TRIM9, SYT1, SYNGR1, and SNAP91 in ALSC9orf72 MN (Welch's t-test). n=3 independent cultures for each hiPSC line. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228
NLGN3: 54413
SLC6A: 6538
SNAP91: 9892
SYNGR1: 9145
SYT1: 6857
TRIM9: 114088"
  },
  {
    "caption": "(G-H) Time course analysis of nuclear pCREBS133 levels and MN survival  in  ALSC9orf72 and Healthy cultures (two-way ANOVA). n=3 independent cultures for each hiPSC line (for each time point). Scale bar: 25 µm. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(A) Both K+  channel blockers exert a neuroprotective effect in ALSC9orf72 cultures by increasing the neurite length of mutant MN (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with each hiPSC line. Scale bar: 50 µm Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(C) Apamin  and XE991 decrease the size of aberrant aggresomes, confirming enhanced autophagy  degradation (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with the ALSC9orf72 I line. Scale bar: 5 Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(E) The load of aggregated SQSTM1/p62 is also reduced by the treatments in ALSC9orf72 cultures (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments for each cell line. Scale bar: 20 µm. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(F) Treatment with the   K+ channel blockers reduces the number of GGGGCC toxic RNA foci in ALSC9orf72 MN. n=3 independent treatments with each hiPSC line (one-way ANOVA followed by Dunnett's multiple comparison test). Scale bar: 5 µm. Dashed line represents the cell soma. Data information: *p<0.05; **p<0.01; ***p<0.001. Error bars represent SEM. Arrow indicates the structure displayed at higher magnification. Exact p-values are reported in Appendix Table S1. ",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(E)  Apamin and XE991 increase the  levels  of pCREBS133 in all the  ALSC9orf72 lines (one-way ANOVA followed by Dunnett's multiple comparison test). n=3 independent treatments with each hiPSC line. Scale bar: 10 µm. Data information: *p<0.05; **p<0.01. Error bars represent SEM. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(F) ALSC9orf72 MN showed an increased number  of  Homer1b/c+  synaptic contacts after treatment with the K+ channel blockers, which in contrast had no significant effect on Healthy MN. n=3 independent treatments with each hiPSC line (two-way ANOVA). Scale bar: 5 µm Data information: *p<0.05; **p<0.01. Error bars represent SEM. Exact p-values are reported in Appendix Table S1.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "PMO   was administered intravenously into adult mdx mice  at 25 or 50 mg/kg/week for 3 weeks with dietary supplementation of glycine  for 3 consecutive days per week prior to PMO   administration. (B) Immunohistochemistry  for dystrophin expression  in body-wide muscles  from mdx mice  treated with PMO  in saline  (PMO-S), PMO-G(IV) or PMO-G (D)(scale bar=100μm).PMO-G (IV) refers to intravenous injection of PMO   in combination with intravenous injection of 5% glycine  every other day for 3 weeks. PMO-G (D) represents intravenous injection of PMO   supplemented with 1% glycine  orally.",
    "ncbi_link": "mdx: 13405"
  },
  {
    "caption": "PMO   was administered intravenously into adult mdx mice  at 25 or 50 mg/kg/week for 3 weeks with dietary supplementation of glycine  for 3 consecutive days per week prior to PMO   administration. (C) Western blot  for dystrophin  expression in body-wide muscles from mdx mice  treated with PMO-G (IV), PMO-G (D) or PMO-S. 0.5µg, 2.5 µg, 5µg, 10µg and 15µg total protein from C57BL/6 and 50 µg of muscle samples from untreated and treated mdx mice  were loaded. α-actinin was used as the loading control. TA-tibialis anterior, Q-quadriceps, G-gastrocnemius, T-triceps, D-diaphragm  and A-abdominal muscle. (D) Quantitative analysis of dystrophin  expression in body-wide muscles from mdx mice  treated with PMO-G (i.v., n=4), PMO-G (D25 and D50, n=3) and PMO-S (n=3) (*P<0.05,**P<0.001; One way-ANOVA post hoc Student-Newman-Keuls test). Data information: Error bars indicate s.e.m. Data shown are representative of biological replicates as specified.",
    "ncbi_link": "mdx: 13405"
  },
  {
    "caption": "Nurr1 (N) and Foxa2 (F) synergistically downregulate SGK1 expression in cultured glia. (A) Up- and downregulated genes in the microarray data for the cultured glia transduced with N+F (vs. mock-transduced control). Sgk1 is marked with an arrow in the top downregulated genes.",
    "ncbi_link": "Foxa2: 15376
Nurr1: 18227
Sgk1: 20393
SGK1: 20393"
  },
  {
    "caption": " Effect of N and F on SGK1 expression in glial cells shown in the microarray (B), RNA-seq (C), Data in (B and C) represent values of fold change (FC) or read count (RC) with color intensities. n=3. One-way ANOVA. Data are represented as mean ± SEM. Significantly different at p= 0.0493*, 0.0092**, 0.0009***. ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " Effect of N and F on SGK1 expression in glial cells shown in the RT-PCR analyses. One-way ANOVA. Data are represented as mean ± SEM. Significantly different at p= 0.0493*, 0.0092**, 0.0009***. ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " N+F-mediated downregulation of NFκB signaling (phosphorylation of p65, p-p65, G) were alleviated by forced SGK1 expression in the VM-glial cultures. ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " H) N+F-mediated downregulation of pro-inflammatory cytokine expression (IL-1β, TNFα, H) were alleviated by forced SGK1 expression in the VM-glial cultures. ",
    "ncbi_link": "IL-1β: 16176
SGK1: 20393
TNFα: 117167"
  },
  {
    "caption": " Glial pro-inflammatory cytokine expression regulated by SGK1 inhibition ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " Glial pro-inflammatory cytokine expression regulated by SGK1 inhibition (J-M) and overexpression (N). ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " mRNA expression of the NLRP3-inflammasome components Nlrp3, Pycard (Asc), and Caspase1. Decreased expression of the components shown in the RNA-seq Data are expressed as mean ± SEM. Significantly different at p=0.0018*, 0.0405**, 0.0039***, 0.0002#, 0.0033##, 0.0099###, 0.0001####, 0.0056+, 0.0398++, 0.0067+++ ",
    "ncbi_link": "Caspase1: 12362
Nlrp3: 216799
Asc: 66824
Pycard: 66824"
  },
  {
    "caption": " B, mRNA expression of the NLRP3-inflammasome components Nlrp3, Pycard (Asc), and Caspase1. Decreased expression of the components shown in the q-PCR analyses in other independent VM-glial cultures treated with the inhibitor (GSK-650394) and sh-Sgk1 and si-Sgk1 (vs. DMSO, sh-control, and si-control, respectively) (B). n=3; Student's t-test. Data are expressed as mean ± SEM. Significantly different at p=0.0018*, 0.0405**, 0.0039***, 0.0002#, 0.0033##, 0.0099###, 0.0001####, 0.0056+, 0.0398++, 0.0067+++ in graph B. ",
    "ncbi_link": "Caspase1: 12362
Nlrp3: 216799
Asc: 66824
Pycard: 66824
Sgk1: 20393"
  },
  {
    "caption": " Expression of CGAS-STING pathway genes in the RNA-seq data. The graph represents log2 RC ratios of [GSK-650394-treated/DMSO-treated control]. ",
    "ncbi_link": "CGAS: 214763
STING: 72512"
  },
  {
    "caption": " H, Expression of Ifnb mRNA, a final product of the CGAS-STING pathway, determined by real-time PCR analyses. Data are represented as mean ± SEM. n=3; student's t-test. Significantly different at p=0.0459#, 0.0305* in graph H. ",
    "ncbi_link": "CGAS: 214763
Ifnb: 15977
STING: 72512"
  },
  {
    "caption": " Ppargc1a (PGC1α) mRNA expression upregulated in VM-glia treated with the SGK1 inhibitors in the RNA-seq data Data are represented as mean ± SEM. n=3; Student's t-test. Significantly different at p=0.0011#, 0.0499* in graph B. ",
    "ncbi_link": "PGC1α: 19017
Ppargc1a: 19017"
  },
  {
    "caption": " B, Ppargc1a (PGC1α) mRNA expression upregulated in VM-glia treated with the SGK1 inhibitors in the q-PCR analysis Data are represented as mean ± SEM. n=3; Student's t-test. Significantly different at p=0.0011#, 0.0499* in graph B. ",
    "ncbi_link": "PGC1α: 19017
Ppargc1a: 19017"
  },
  {
    "caption": " VM-glial cultures were transduced with sh-Sgk1 (or sh-cont) lentivirus. Medium was condition in sh-Sgk1-glia (or sh-cont-glia), and the conditioned medium (CM) treatment effects on neuronal SNCA aggregation were assessed by WB ",
    "ncbi_link": "Sgk1: 20393"
  },
  {
    "caption": " VM-glial cultures were transduced with sh-Sgk1 (or sh-cont) lentivirus. Medium was condition in sh-Sgk1-glia (or sh-cont-glia), and the conditioned medium (CM) treatment effects on neuronal SNCA aggregation and p-129-SNCA immunocytochemical analyses. Data are represented as mean ± SEM. n=3. Significantly different at p=0.00003*, 0.0003**, 0.0012***, 0.00004****, 0.0321# in graph G and p=0.0052* in graph H. ",
    "ncbi_link": "Sgk1: 20393"
  },
  {
    "caption": " Glia derived from mouse VM were transduced with sh-Sgk1 (B) or SGK1 (CMV-Sgk1, C), and co-cultured with VM-derived mDA neurons. Seven days after co-culture, cells were exposed to H2O2 (500µM, 3hr) or not (-), and then mDA neuron viability (TH+ cell counts) and neurite degeneration (TH+ fiber lengths) were estimated. Data are represented as mean ± SEM; n=4 culture coverslips. Student's t-test. Significantly different at p=0.033*, 0.0412**, 7.44E-23#,1.39E-23## in graph B and p=0.0489*, 0.0366**, 0.0078## in graph C. ",
    "ncbi_link": "Sgk1: 20393
SGK1: 20393"
  },
  {
    "caption": " Glial neurotrophic functions potentiated by SGK1 downregulation were mediated in a paracrine manner. VM-glia transduced with sh-Sgk1 (or sh-cont as a control) were challenged with H2O2+LPS for 3hr or not. Glial conditioned medium (GCM) was prepared in each glial culture condition and administered to mDA neurons primarily cultured from mouse VM (E) Cell viability of the neuronal cells was estimated using CCK8 assays and TuJ1+ cell counts. Data are represented as mean ± SEM. n=3 cultures; One-way ANOVA. Significantly different at p=0.0002*, 3.29E-08**, 0.0003***, 3.66E-06#, 0.0029## (TuJ1+ cell counting), 0.0127+, 5.98E-06++, 0.0002+++, 0.0005&, 0.0078&& (CCK8 assays) in graph E. ",
    "ncbi_link": "SGK1: 20393
Sgk1: 20393"
  },
  {
    "caption": " A and B, Efficiency of AAV9-mediated gene delivery. AA9 viruses expressing the reporter GFP gene were stereotaxically injected into the SN of mice, and GFP expression in astrocytes, microglia, and neuronal cells was quantified. Data are represented as mean ± SEM. n=3 mice (>5 randomly selected microscopic fields per animal were counted). Significantly different at p=0.006*, 5.1E-09#, 5.36E-09+ in graph B. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " SGK1 knockdown effect in vivo by treatment with shSgk1-AAV9. Total SGK1 mRNA levels were estimated in the midbrain SN of the PD mice injected with shSgk1(shControl as control) AAV9 using real time-PCR (D).",
    "ncbi_link": "SGK1: 20393
Sgk1: 20393"
  },
  {
    "caption": " Cell type-specific SGK1 knockdown was estimated by counting SGK1-immuonoreactivity in neuron (MAP2+), astrocyte (GFAP+), and microglia (Iba1+) populations (E). ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " Histologic assessment of p129-SNCA immunoreactivity ( I,J), TH+ mDA neuron counts (I,K), neurite lengths (L), and cell body sizes (M) in the SN Significantly different at p=0.0001* in graph J, p=2.35E-25#, 1.09E-16##, 4.36E-08* in graph K and p=1.5E-40#, 1.08E-24##, 2.32E-07* in graph L and p=9.07E-20#, 2.59E-16##, 0.05* in graph M and p=4.62E-22#, 5.11E-12##, 3.49E-06* (TH), n= 7 sh-SGK1-AAV9-treated PD mice, 7 sh-cont-AAV9-treated PD mice, and 8 SNCA-untreated mice. Data are represented as mean ± SEM. One-way ANOVA. Scale bar, 100µm. ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": " Histologic assessment of TH+ and DA transporter (DAT) fiber intensities in the striatum n= 7 sh-SGK1-AAV9-treated PD mice, 7 sh-cont-AAV9-treated PD mice, and 8 SNCA-untreated mice. Data are represented as mean ± SEM. One-way ANOVA. Scale bar, 100µm. ",
    "ncbi_link": "SGK1: 20393"
  },
  {
    "caption": "(E and F) HepG2 cells infected with lentivirus expressing p53 sgRNA or control sgRNA were treated with ethanol-d6 (5 mM) or ethanol-1-13C (5 mM) for 0.5 h. Relative acetate m+3 and acetate m+1 levels (E-F, top panels) were examined. Protein levels of p53 and ALDH2 (E-F, bottom panels) were analyzed by western blot.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(H-J) HepG2 cells infected with lentivirus expressing p53 sgRNA or control sgRNA were treated with doxorubicin (2 ng/mL) (H) nutlin3α (10 μM) (I) or cyanamide (1 mM) (J) for 24 h. Relative enzymatic activity of ALDH2 was examined (top panel). Protein expression was determined by western blot analysis (bottom panel).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(P-R) p53+/+ and p53-/- mice were injected intraperitoneally with ethanol-d6 (2 g/kg) for 0.5 h. Relative acetate m+3 levels in mouse liver tissues (P) and mouse serum (Q), and relative hepatic acetyl-CoA (R) were examined.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(S) Mouse hepatocyte isolated from p53+/+ and p53-/- mice and lysates were treated with or without cyanamide (1mM). Relative acetyl-CoA level (top panel) and protein expression (bottom panel) were measured. (T) CCC-HEL-1 cells transfected with control siRNA or p53 siRNA were treated with or without cyanamide (1mM). Relative acetyl-CoA level (top panel) and protein expression (bottom panel) were analyzed.",
    "ncbi_link": "p53: 7157
p53: 22059"
  },
  {
    "caption": "(U-X) HepG2 cells infected with lentivirus expressing p53 sgRNA or control sgRNA were transfected with control siRNA or ALDH2 siRNA and were treated with ethanol-d6 (5 mM) (U) or ethanol-1-13C (5 mM) (X) for 0.5 h. (U) Relative acetate m+3 and acetyl-CoA m+3 levels are shown. (X) Relative acetate m+1 and acetyl-CoA m+3 levels were examined. Protein levels of p53 and ALDH2 were analyzed by western blot (V- W).",
    "ncbi_link": "ALDH2: 217
p53: 7157"
  },
  {
    "caption": "(C) Lysates from mice liver tissues (WT, p53-/- and ALDH2-/-) were immunoprecipitated using p53 or ALDH2 antibody, and bound proteins were analyzed by western blot.",
    "ncbi_link": "ALDH2: 11669
p53: 22059"
  },
  {
    "caption": "(G) HepG2 cells were infected with lentivirus expressing ALDH2 sgRNA or control sgRNA and overexpressed hygromycin-resistant ALDH2 mut312-323 in ALDH2-knockout cell lines. The cells were then transfected with control siRNA or p53 siRNA for 48 h and treated with ethanol (5 mM) for 0.5 h and relative ALDH2 enzymatic activities were examined. Protein expression was analyzed by western blot.",
    "ncbi_link": "ALDH2: 217
p53: 7157"
  },
  {
    "caption": "(H) Lysates from 293T cells transfected with HA-ALDH2, Flag-ALDH2 and increasing amounts of GST-p53 or vector control (-) as indicated were immunoprecipitated using anti-Flag M2 affinity gels, and bound proteins were analyzed by western blot.",
    "ncbi_link": "ALDH2: 
Flag: 
GST: 
HA: 
ALDH2: 217
p53: 7157"
  },
  {
    "caption": "(I) HepG2 cells infected with lentivirus expressing ALDH2 sgRNA or control sgRNA were treated with ethanol (5 mM) for 0.5 h and cell lysates were treated with disuccinimidyl suberate (DSS) or DMSO for 0.5 h and protein levels of p53 and ALDH2 were examined.",
    "ncbi_link": "ALDH2: 217"
  },
  {
    "caption": "(A-B) HepG2 cells infected with lentivirus expressing p53 sgRNA or control sgRNA under glucose or pyruvate deprivation and cell lysates were used to measure ALDH2 activities (A, B, top panels) and examine p53 and ALDH2 proteins (A, B, bottom panels).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(F) HepG2 cells were infected with lentivirus expressing ALDH2 sgRNA or control sgRNA and overexpressed hygromycin-resistant ALDH2-N186A, E285A, C319A in ALDH2-knockout cell lines. Cells were digested and cell lysates were incubated with the indicated doses of pyruvate for 1 hour on ice and 0.5 hour at room temperature, followed by pronase digestion. ALDH2 proteins were analyzed by western blot. Relative ALDH2/Actin ratios are shown.",
    "ncbi_link": "ALDH2: 217"
  },
  {
    "caption": "(H-J) HepG2 cells were infected with lentivirus expressing ALDH2 sgRNA or control sgRNA and overexpressed hygromycin-resistant ALDH2 N186A in ALDH2-knockout cell lines. The cells were treated with pyruvate (1 mM) for 24 h. Relative ALDH2 activity (H, top panel), acetate (I) and acetyl-CoA (J) were measured. The expression of p53 and ALDH2 were analyzed by western blot (H, bottom panel).",
    "ncbi_link": "ALDH2: 217"
  },
  {
    "caption": "Relative mRNA levels of IL-6, were analyzed. were examined. Data in are from n=5 mice per group.",
    "ncbi_link": "IL-6: 16193"
  },
  {
    "caption": "Relative mRNA levels of , IL-1β, TNF-α, Cxcl1, Cxcl2, Col1a1 were analyzed. Data in are from n=5 mice per group.",
    "ncbi_link": "Col1a1: 12842
Cxcl1: 14825
Cxcl2: 20310
IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "(M-O) WT, p53−/−, ALDH2−/− and p53−/−ALDH2−/− C57BL/6N male mice were injected intraperitoneally with ethanol-d6 (2 g/kg) for 0.5 h as shown in Figure 1N. Relative acetate and acetate m+3 levels in mouse liver tissues (M) and mouse serum (N) were examined. (O) Relative acetyl-CoA and acetyl-CoA m+3 levels in mouse liver tissues were measured.",
    "ncbi_link": "ALDH2: 11669
p53: 22059"
  },
  {
    "caption": "(C-D) p53+/+ and p53-/- mice were injected intraperitoneally with ethanol-d6 (2 g/kg) for 1 h. Chromatin fractions of liver tissues were subjected to ChIP-seq assay using H3K9ac antibody (left panel), H3K27ac antibody (right panel). Heat map of H3K9ac/H3K27ac binding signal (rows) from -1 kb to +1 kb surrounding the centre of H3K9ac/H3K27ac-binding sites for ChIP-seq tags (C). Heatmap of H3K9ac/H3K27ac binding signal (rows) from -1 kb to +1 kb surrounding the centre of H3K9ac/H3K27ac-binding sites for ChIP-seq tags of fatty acid metabolism related genes (D). For ChIP-seq analysis , there were no technical replicates for anti-H3K9ac or anti-H3K27ac.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(F) ChIP assays with H3K9ac antibody and H3K27ac antibody or IgG in WT and p53−/− mice injected intraperitoneally with ethanol-d6 (2 g/kg) or saline for 1 h. Bound SCD1 response elements (RE) were analyzed by qRT-PCR. Data in F are from n=3 biological independent samples.",
    "ncbi_link": "SCD1: 20249
p53: 22059"
  },
  {
    "caption": "WT, p53−/−, ALDH2−/− and p53−/−ALDH2−/− C57BL/6N male mice were fed control diet and ethanol diet as shown in Fig.4A. Relative mRNA level of SCD1 (G, top panel) was analyzed. Protein levels of p53, ALDH2, SCD1, Histone H3 and Ac-H3, caspase 3, cleaved caspase 3, p21 (G, bottom panel) in mice liver tissues were examined. Data in G are from n=5 technical replicates from one of three independent experiments with similar results.",
    "ncbi_link": "ALDH2: 11669
SCD1: 20249
p53: 22059"
  },
  {
    "caption": "WT and p53−/− mice were injected with adenovirus expressing SCD1 shRNA or control shRNA via tail vein. After 7 days, WT and p53−/− mice were treated as described in the methods to establish a mouse model of chronic-binge ethanol consumption. (C) Protein levels of p53 and SCD1 were examined by western blot. level were examined.",
    "ncbi_link": "SCD1: 20249
p53: 22059"
  },
  {
    "caption": "WT and p53−/− mice were injected with adenovirus expressing SCD1 shRNA or control shRNA via tail vein. After 7 days, WT and p53−/− mice were treated as described in the methods to establish a mouse model of chronic-binge ethanol consumption. Relative hepatic triglyceride level(D), relative serum ALT (E, left panel) and AST (E, right panel) level were examined.",
    "ncbi_link": "SCD1: 20249
p53: 22059"
  },
  {
    "caption": "WT, ALDH2−/− and p53-/-ALDH2−/− mice were injected with adeno-associated virus expressing AAV-GFP or AAV-SCD1 via tail vein. After 7 days, WT, ALDH2−/− and p53-/-ALDH2−/− mice were treated as described in the methods to establish a mouse model of chronic-binge ethanol consumption. (H) Protein levels of p53 and SCD1 are shown.",
    "ncbi_link": "GFP: 
ALDH2: 11669
SCD1: 20249
p53: 22059"
  },
  {
    "caption": "WT, ALDH2−/− and p53-/-ALDH2−/− mice were injected with adeno-associated virus expressing AAV-GFP or AAV-SCD1 via tail vein. After 7 days, WT, ALDH2−/− and p53-/-ALDH2−/− mice were treated as described in the methods to establish a mouse model of chronic-binge ethanol consumption. Relative hepatic triglyceride level (I), relative serum ALT (J, left panel) and AST (J, right panel) were examined.",
    "ncbi_link": "GFP: 
ALDH2: 11669
SCD1: 20249
p53: 22059"
  },
  {
    "caption": "b, Shift in phase durations of RPE cells overexpressing Myc. boxplots representing the distributions of phase durations in untreated cells are underlaid for comparison. *, P < 1 × 10-5; **, P < 1 × 10-10; ***, P < 1 × 10-20, 2-sided Kolmogorov-Smirnov test. Number of cells: Myc, n = 116",
    "ncbi_link": "Myc: 4609"
  },
  {
    "caption": "c, Pairwise correlation between cell cycle phase durations of RPE cells overexpressing Myc. Number of cells: Myc, n = 116",
    "ncbi_link": "Myc: 4609"
  },
  {
    "caption": "j, Shifts in phase durations for RPE cells overexpressing cyclin D. A boxplot representing the distributions of durations in untreated cells is underlaid for comparison. *, P < 1 × 10-5, 2-sided Kolmogorov-Smirnov test. (n = 113 cells).",
    "ncbi_link": "cyclin D: 595"
  },
  {
    "caption": "k, Pairwise correlation between cell cycle phase durations upon overexpression of cyclin D. P indicates P-value.",
    "ncbi_link": "cyclin D: 595"
  },
  {
    "caption": "Representative images of LINC00115 expression in clinical GBM tumors and adjacent tissue using RNAscope analysis. Images are representative of two independent experiments. Scale bars: 50 μm.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "Kaplan-Meier analysis of patients with high versus low LINC00115-expressing GBM tumors from B. Median survival (in months): low, 13.9; high, 8.1. Black bars, censored data. Data information: , *, p < 0.05, by log-rank test.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "Expression levels of LINC00115 are higher in LGG (low grade gliomas) versus normal brain tissues and GBM versus LGG. Expression data of LINC00115 were downloaded from the REMBRANDT dataset. Data are presented as mean ± SEM. **, p < 0.01, ***, p < 0.001, by two-tailed t test.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "E to G. Kaplan-Meier analysis of patients with high versus low LINC00115-expressing Grade III and GBM tumors from the REMBRANDT (E) or the TCGA (G) 26[], and GBM from GSE83300 50[] (F) datasets. Median survival (in months) in E: low, 20.2; high, 15.9; in F: low, 19.4; high, 13.0; in G: low, 33.2; high, 25.4. Black bars, censored data. Data information: , *, p < 0.05, by log-rank test.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "qRT-PCR analysis of LINC00115 knockdown using two different shRNAs, shL115-1 and shL115-2 in 1123 and 528 GSCs. Data information: data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, **, p < 0.01, by One-way ANOVA",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "Effects of LINC00115 knockdown on GSC proliferation (B) data are representative of three independent experiments. Error bars, ± SD. *, by two-tailed t-test in B.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "C. Effects of LINC00115 knockdown on neuro-like sphere formation (C). Data information: data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, **, p < 0.01, by One-way ANOVA in",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "H. Immunofluorescence (IF) analysis of Nestin expression in 1123 GSC control and LINC00115 knockdown xenograft tumors from F. Images are representative of two independent experiments. Scale bars: 50 μm.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "B and C. MS2-RIP followed by qRT-PCR analysis of endogenous microRNAs association with LINC00115. 12XMS2 empty vector, LINC00115-12XMS2, or LINC00115-mut- 12XMS2 with Flag-tagged MS2 were co-transfected into 1123 GSCs. Data information data are representative of three independent experiments. Error bars, ± SD. , ***, p < 0.001, by two-tailed t-test.",
    "ncbi_link": "Flag: 
MS2: 
LINC00115: 79854"
  },
  {
    "caption": "E. RNA pull-down and qRT-PCR assays of LINC00115 binding with miR-200s. GSC1123 cell lysates were incubated with biotin-labeled LINC00115. Data information data are representative of three independent experiments. Error bars, ± SD. p < 0.05, **, p < 0.01, by One-way ANOVA.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "F. Luciferase activity analysis of 1123 GSCs co-transfected with miR-200s and luciferase reporters containing LINC00115 WT, mutant, or empty vector (EV). Data information: data are representative of three independent experiments. Error bars, ± SD. p < 0.05, **, p < 0.01, by One-way ANOVA.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "A and B. Correlation of expression between LINC00115 and ZEB1 from TCGA GBM RNA-Seq dataset (A) and REMBRANDT GBM array dataset (B). ***, p < 0.001, by two-tailed t-test.",
    "ncbi_link": "LINC00115: 79854
ZEB1: 6935"
  },
  {
    "caption": "C. LINC00115 knockdown reduced ZEB1 mRNA expression in 1123 and 528 GSCs. Data information: , data are representative of three independent experiments. Error bars, ± SD. **, p < 0.01, by One-way ANOVA",
    "ncbi_link": "LINC00115: 79854
ZEB1: 6935"
  },
  {
    "caption": "D. Effects of LINC00115 knockdown on ZEB1, vimentin, and E-cadherin protein expression. Data information: data are representative of three independent experiments. Error bars, ± SD. **,",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "E. Effects of re-expression of shRNA-resistant LINC00115 WT (L115-WT), miR-200 binding mutant (L115-mut) with or without miR-200b on ZEB1 signaling activation. Data information data are representative of three independent experiments. Error bars, ± SD.",
    "ncbi_link": "LINC00115: 79854
miR-200: 406984
miR-200b: 406984"
  },
  {
    "caption": "F. Neuro-like sphere formation assay of effects of re-expression of shRNA-resistant LINC00115 WT and mutant with or without miR-200b. Data information: data are representative of three independent experiments. Error bars, ± SD. **, p < 0.01, by two-tailed t-test in F.",
    "ncbi_link": "LINC00115: 79854
miR-200b: 406984"
  },
  {
    "caption": "H and I. GSEA of EMT signature genes using ranked gene expression changes in TGF-β1-treated 1123/shLINC00115 GSCs versus the control (H) or in 1123 GSCs with ectopic expression of LINC00115 or an empty vector (EV) (I). NES, normalized enrichment score.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "LINC00115 knockdown reduced ZNF596 mRNA expression. Data information: In data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, by One-way ANOVA",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "LINC00115 knockdown reduced ZNF596 protein (D) expression. Data information: data are representative of three independent experiments. Error bars, ± SD.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "E. Effects of exogenous ZNF596 expression on LINC00115 knockdown-inhibited ZNF596 protein expression. Data information: data are representative of three independent experiments. Error bars, ± SD.",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "F. ZNF596 overexpression had no effect on LINC00115 expression. Data information data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, by One-way ANOVA",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "G. Expression of exogenous ZNF596 rescued LINC00115 knockdown-inhibited cell proliferation. Data information: data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05 , by two-tailed t-test in G.",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "H. Representative H&E staining images of mouse brain sections with 1123/shC and 1123/shL115 GSC tumor xenografts with empty vector (EV) or ectopic ZNF596 expression. Images represent results of five mice per group of two independent experiments. Scale bars: 1 mm. I. Quantification of tumor size in H. ",
    "ncbi_link": "ZNF596: 169270"
  },
  {
    "caption": "J and K. Correlation of expression between LINC00115 and ZEB1 from TCGA GBM RNA-Seq dataset (J) and REMBRANDT GBM array dataset (K). **, p < 0.01, by two-tailed t-test.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "Expression of shRNA-resistant LINC00115 WT but not mutant or empty vector (EV) rescued LINC00115 shRNA-inhibited ZNF596 mRNA (A) expression in 1123 GSCs.",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "Expression of shRNA-resistant LINC00115 WT but not mutant or empty vector (EV) rescued LINC00115 shRNA-inhibited ZNF596 protein (B) expression in 1123 GSCs.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "D. MS2-RIP followed by qRT-PCR for endogenous microRNAs association with ZNF596. 12XMS2 empty vector, ZNF596-5'-UTR-WT-12XMS2, or ZNF596-5'-UTR-mut -12XMS2 with Flag-tagged MS2 were co-transfected into 1123 GSCs.",
    "ncbi_link": "Flag: 
MS2: 
ZNF596: 169270"
  },
  {
    "caption": "F. Luciferase activity in 1123 GSCs co-transfected with miR-200s and luciferase reporters containing ZNF596 5'-UTR WT, mutant, or empty vector (EV).",
    "ncbi_link": "ZNF596: 169270"
  },
  {
    "caption": "GSEA of EZH2-targeted signature genes using ranked gene expression changes in 1123 GSCs with ZNF596 sgRNA or a control sgRNA. NES, normalized enrichment score.",
    "ncbi_link": "EZH2: 2146
ZNF596: 169270"
  },
  {
    "caption": "qRT-PCR analysis of effect of ZNF596 knockout on EZH2 expression. Data information: data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, **, p < 0.01, ***, p < 0.001, by One-way ANOVA",
    "ncbi_link": "EZH2: 2146
ZNF596: 169270"
  },
  {
    "caption": "ZNF596 knockout impaired EZH2 expression, its downstream H3K27me3, and STAT3 phosphorylation in 1123 and 528 GSCs. Data information , data are representative of three independent experiments. Error bars, ± SD.",
    "ncbi_link": "ZNF596: 169270"
  },
  {
    "caption": "LINC00115 regulated ZNF596/EZH2/STAT3 signaling. 1123 and 528 GSCs were treated with or without EZH2 inhibitor GSK343 (3 μM) for 6 Data information: data are representative of three independent experiments. Error bars, ± SD.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "LINC00115 and ZNF596 regulate EZH2 promoter activity. Data information: data are representative of three independent experiments. Error bars, ± SD. , by two-tailed t-test",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "ChIP-qPCR analysis of ZNF596 binding with the EZH2 promoter. Data information: data are representative of three independent experiments. Error bars, ± SD. *, p < 0.05, **, p < 0.01, ***, p < 0.001, by One-way ANOVA",
    "ncbi_link": "EZH2: 2146
ZNF596: 169270"
  },
  {
    "caption": "EZH2 inhibitor GSK343 impaired ZNF596 overexpression-reversed and LINC00115 knockdown-inhibited neuro-like sphere formation. 1123 and 528 GSCs with an inducible ZNF596 shRNA were treated with or without Dox (2 μg/ml) and/or EZH2 inhibitor GSK343 (1 μM) for 7 days. Data information: data are representative of three independent experiments. Error bars, ± SD. by two-tailed t-test",
    "ncbi_link": "LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "Representative images of RNAscope for LINC00115 and IHC for ZEB1 and ZNF596 expression in two GBM specimens, Sample #1 (positive) and Sample #2 (negative). Scale bar, 50 μm. Images are representative of two independent experiments.",
    "ncbi_link": "LINC00115: 79854"
  },
  {
    "caption": "Correlation of detected expression between ZEB1 or ZNF596, and LINC00115 from a separate cohort of a total of 75 paraffin-embedded clinical GBM samples. Statistical analysis was performed by Chi-square test.",
    "ncbi_link": "ZEB1: 
LINC00115: 79854
ZNF596: 169270"
  },
  {
    "caption": "Kaplan-Meier survival analysis of patients with GBM tumors expressing high or low levels of LINC00115 with high or low levels of ZEB1 or ZNF596 expression. Median survival (in months): LINC00115hi/ZEB1hi, 5.4; LINC00115lo/ZEB1lo, 27.9; LINC00115hi/ZNF596hi, 4.2; LINC00115lo/ZNF596lo, 23.8. Statistical analysis was performed by log-rank test.",
    "ncbi_link": "LINC00115: 79854
ZEB1: 6935
ZNF596: 169270"
  },
  {
    "caption": "(C) Heatmaps showing changes in expression of key myogenic (MYOD, MYOGENIN), perivascular (PDGFRB, NG2, CD146, ALPL) and NOTCH target (HEY1, HES1) genes upon treatment with DLL4 & PDGF-BB in mMuSC-derived myoblasts (left), human myoblasts (middle) and hiMPs (right). Clustering was performed by genes/probes with Pearson correlation. Colour scale based on z-scores: red regions indicate high expression whilst blue regions indicate low expression. Dendrograms indicate the similarity of clusters as well as the orders in which clusters were assembled.",
    "ncbi_link": "ALPL: 11647
NG2: 121021
HES1: 15205
HEY1: 15213
CD146: 84004
MYOD: 17927
MYOGENIN: 17928
PDGFRB: 18596"
  },
  {
    "caption": "B, CSF-1 mRNA expression was measured in MC38 and KPC cells exposed to 10Gy IR compared with mock irradiated cells. Cells were harvested at 24, 48 and 72 hours after irradiation and RNA expression was analysed by RT-qPCR. Data are presented as mean ± SEM and analysed by Kruskal-Wallis test with Dunn's multiple comparison (n=3).",
    "ncbi_link": "CSF-1: 12977"
  },
  {
    "caption": "HEp-2 cells remained untreated or were incubated with 20 µg/ml of whole cell extract of Y. pseudotuberculosis expressing full-length CNF1, CNFY or the N- or C-terminally deleted toxin variants at 37°C for 4 h. The cells were thoroughly washed, pelleted, lysed and the toxin variants bound to the cells were identified by western blotting using an anti-Flag antibody.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "Left upper and right panel: HEp-2 cells re­mained untreated or were incubated with 20 µg/ml of whole cell extract of Y. pseudotuberculosis expressing full-length CNFY or the N- or C-terminally deleted toxin variants for 4 h. Cells were lysed and the de­amidation of RhoA was analyzed by the shift of the modified Rho GTPase band in SDS PAGE gels; left lower panel: HEp-2 cells were lysed and the cell extracts were incubated with full-length CNFY or the N-ter­minally deleted toxin variants for 4 h. The de­amidation of RhoA in the cell extracts was analyzed by the mobility shift of the modified Rho GTPase on SDS PAGE after detection with anti-RhoA antibodies.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "HEp-2 cells were incubated with 20 µg/ml of whole cell extract of Y. pseudotuberculosis expressing full-length CNFY or the N- or C-terminally deleted toxin variants for 24 h. The cell nuclei were strained with DAPI (blue) and the actin cytoskeleton was stained using FITC-phalloidin (green). The formation of large, multinuclear cells was ob­served by fluorescence micro­­scopy and the formation of thick actin stress fibers and membrane actin folding were only observed with CNFY-treated cells. The white scale bar is 40 µm. Cells incubated with extracts of YP147 (ΔcnfY) harboring the empty expression vector were used as negative controls.",
    "ncbi_link": "cnfY: 
CNFY: "
  },
  {
    "caption": "HEp-2 cells were incubated with 20 µg/ml of whole cell extract of Y. pseudotuberculosis expressing full-length CNFY, N- or C-terminal deletion variants fused to GFP (green) for 90 or 180 min. Cells were fixed and processed for fluorescence microscopy. The red fluorescent signal represents late endosomes (CellLight Late Endosomes-RFP (Rab7a)). Nuclei were stained with DAPI (blue). A merged image of the different channels is shown, and smaller images are magnified views of boxed areas. White scale bar is 10 µm.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "Nitrocefin (2 mM) was added to the supernatant from 25°C overnight Yersinia cultures expressing the indicated CNFY derivatives to determine β-lactamase activity by measuring changes in absorbance at 390 nm (yellow) and 486 nm (red). The data represent the mean ± SD of three independent experiments, carried out in triplicates.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "The viability of Y. pseudotuberculosis YPIII expressing the indicated CNFY derivatives was assessed in equalized bacterial cultures using the BacTiter-Glo Microbial Cell Viability Assay kit (Promega). The data represent the mean ± SD of three independent experiments, carried out in triplicates.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "Comparative analysis of RhoA activation in HEp-2 cell lysate by CNFY and the recombinant D4-5 protein. Purified CNFY or the D4-5 fragment (1 µM) was added to extracts of HEp-2 cells and incubated for 10, 20, 30 or 60 min. De­amidation of RhoA was analyzed by the shift of the modified Rho GTPase band in SDS PAGE gels after detection with anti-RhoA antibodies.",
    "ncbi_link": "CNFY: "
  },
  {
    "caption": "(J) IgM-BCR immunoprecipitation to investigate recruitment of endophilin A2 to activated BCRs. Anti-endophilin A2 blots detect overexpressed endophilin A2-GFP in streptavidin immunoprecipitates and total supernatants from anti-IgM-biotin-stimulated Ramos and DG75  cells. Representative experiment and quantification from 3 independent pulldowns in WT, BLNK- or GRB2-knockout (KO)  DG75 cells.  Pulldown  intensity is calculated as a percentage of total endophilin A2 protein and normalized to WT in each experiment. Data show mean and SEM; p values calculated using one-way ANOVA.",
    "ncbi_link": "GFP: 
BLNK: 29760
GRB2: 2885
endophilin A2: 6455"
  },
  {
    "caption": "(C) Surface levels of MHCII, BAFFR, CD40  and LPAM1 in Sh3gl1-/- and WT littermates. N = 4-5 mice. P, statistical significance from unpaired t tests. Data show mean ± SEM.",
    "ncbi_link": "Sh3gl1: 20405"
  },
  {
    "caption": "(A) Soluble anti-IgM internalization in CRISPR-targeted follicular B cells. N = 11- 12  mice. Data show mean ± SEM. P, statistical significance from two-way ANOVA. (B) Soluble anti-IgD internalization. N = 3  mice. Data show mean ± SEM. P, statistical significance from two-way ANOVA. (C) Soluble anti-IgG internalization in GC B cells from  SRBC-immunized mice. N = 4 mice. Data show mean ± SEM. P, statistical significance from two-way ANOVA. ",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(C-D) Isolated naïve B cells from CRISPR-targeted chimeras after 3-day culture in stated cytokines. (C)  mCherry percentage in targeted primary cell cultures. N = 15  mice. *p<0.05, **p<0.01, ****p<0.0001 using two-way ANOVA. (D) AnnexinV  surface stain in targeted cells. N = 3-4 mice. Data information: All data show means ± SEM.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(G) Oxygen consumption rate (OCR) in CRISPR-targeted Ramos cells. N = 2 independent infections. P, two-way ANOVA of basal and maximum OCR. (H)  OCR in  B cells isolated from Sh3gl1-/- and WT littermates. N = 9 mice. P, two-way ANOVA of basal and maximum OCR. ",
    "ncbi_link": "CRISPR: 
Sh3gl1: 20405"
  },
  {
    "caption": "Cell cultures with full RPMI media supplemented with 50 μg/ml  FeSO4 or 5 μM hemin chloride. (J) SH3GL1-targeted Ramos cells. N = 4 independent infections. P, statistical significance from two-way ANOVA from both treatments versus RPMI. (K) Control sgRNA-targeted Ramos cells.",
    "ncbi_link": "SH3GL1: 6455"
  },
  {
    "caption": "(O) TfR internalization assay in Ramos cells using biotinylated  anti-CD71. 4 independent CRISPR infections in 2 experiments. P, significance calculated using two-way ANOVA and indicated in corresponding color.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(P,Q) Mouse transferrin internalization in B cells  from SRBC-immunized WT and Sh3gl1-/- littermates. N = 7 mice per genotype in 2 experiments. P, statistical significance analyzed using two-way ANOVA. (P) Naïve B cells. (Q) GC B cells.",
    "ncbi_link": "Sh3gl1: 20405"
  },
  {
    "caption": "AGS cells were infected with H. pylori P1 wild‑type or isogenic ∆HP0857 (mutated in the gmhA gene) strains. Total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "gmhA: 56917658"
  },
  {
    "caption": "Parental AGS, ALPK1‑KO and TIFA‑KO cells were infected with H. pylori for the times shown. Total cell lysates were analyzed by immunoblotting using the indicated antibodies. CagA demonstrated a similar infection rate of the different cells. Asterisk denotes an unspecific band and the arrow indicates the band corresponding to phosphorylated p100.",
    "ncbi_link": "ALPK1: 80216
TIFA: 92610"
  },
  {
    "caption": "Total RNA was isolated from ALPK1‑KO cells and analyzed using quantitative RT‑PCR for the ALPK1 transcript. Data shown depict the average of triplicate determinations normalized to the RPL13A housekeeping gene. Error bars denote RQ ± RQmin/RQmax.",
    "ncbi_link": "ALPK1: 80216
RPL13A: 23521"
  },
  {
    "caption": "TIFA-KO cells were transfected with His‑tagged recombinant TIFA protein 24 h prior to H. pylori infection. Co‑IP with an anti‑His antibody was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies. Asterisk denotes an unspecific band and the arrow indicates the TRAF2 band.",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "AGS and ALPK1-KO cells were infected with H. pylori for the times shown. Co‑IP with an anti‑TRAF6 antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "ALPK1: 80216"
  },
  {
    "caption": "AGS and TIFA-KO cells were infected with H. pylori for the times shown. Co‑IP with an anti‑TRAF6 antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "AGS and TIFA-KO cells were treated with 30 ng/ml IL-1β for the times shown. Co‑IP with an anti‑TRAF6 antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "TIFA-KO cells were transfected with His‑tagged recombinant TIFA protein 24 h prior to H. pylori infection or treatment with 30 ng/ml LTα1β2. Co‑IP with an anti‑His antibody was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "AGS and ALPK1-KO cells were infected with H. pylori for the times shown. Co‑IP with an anti‑TIFA antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "ALPK1: 80216"
  },
  {
    "caption": "AGS and TIFA-KO cells were infected with H. pylori for the times shown. Co‑IP with an anti‑TRAF2 antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "AGS cells were transfected with siRNA against cIAP1. Co‑IP with an anti‑TIFA antibody or isotype‑matched antibody (IgG) was performed. Eluates and total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "cIAP1: 329"
  },
  {
    "caption": "TIFA-KO cells were transfected with empty vector plasmid (pCMV6), wild‑type human (phTIFA), phosphorylation‑defective mutant (pT9A) or TRAF6 binding‑defective mutant (pE178A) FLAG‑tagged TIFA plasmids. Total cell lysates were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "TIFA: 92610
TRAF6: 7189"
  },
  {
    "caption": "TIFA-KO cells were transfected with empty vector plasmid (pCMV6), wild‑type human (phTIFA), phosphorylation‑defective mutant (pT9A) or TRAF6 binding‑defective mutant (pE178A) FLAG‑tagged TIFA plasmids. Total cell lysates were separated by native gel electrophoresis under non-reducing conditions.",
    "ncbi_link": "TIFA: 92610
TRAF6: 7189"
  },
  {
    "caption": "In TIFA‑KO cells transiently expressing TIFA‑tdTomato, co-localization of TRAF6 (A), TRAF2 (B), cIAP1 (C) and TRAF3 (D) with TIFA-tdTomato, which formed TIFAsomes upon infection with H. pylori P1 wild‑type strain, were detected by immunofluorescence staining. The nuclei were counterstained with DAPI. Scale bar = 10 µm. TIFA‑KO cells transiently expressing TIFA‑tdTomato were infected with H. pylori P1 strain mutated in the gmhA gene (∆HP0857). Scale bar = 10 µm.",
    "ncbi_link": "gmhA: 56917658
TIFA: 92610"
  },
  {
    "caption": "Colonic organoids grown from Lgr5-EGFP-IRES-CreERT2 mice were treated with an AhR agonist (10 nM TCDD) or antagonist (10 µM CH223191) for 3 d. (A) Induced Cyp1a1 mRNA expression in response to different treatments (n=3 per group).",
    "ncbi_link": "EGFP: 
Cre: 2777477
Cyp1a1: 13076
ER: 2099
Lgr5: 14160"
  },
  {
    "caption": "Colonic organoids grown from Lgr5-EGFP-IRES-CreERT2 mice were treated with an AhR agonist (10 nM TCDD) or antagonist (10 µM CH223191) for 3 d. (B) Assessment of GFP+ stem cell percentages (n=3 replicates per treatment). Bars with different letters are significantly different (p<0.05).",
    "ncbi_link": "EGFP: 
Cre: 2777477
ER: 2099
Lgr5: 14160"
  },
  {
    "caption": "(D) Flow cytometry analysis of GFP+Tomato+ and Tomato+ cells in the large intestine of AhR wild type (Lgr5-GFPCreERT2 X Tomatof/f, GT) and AhR knock out (AhRf/f X Lgr5-GFPCreERT2 X Tomatof/f, HGT) mice. Top left panel shows representative cells from WT negative control animal (no GFP or Tomato expression). Top right panel shows Tomato only control (CDX2P-CreERT2 X Tomatof/f). Middle panels represent DMSO or TCDD treatment in AhR WT mice, respectively. Mice were gavaged every other day, 4 times total, with vehicle or TCDD (25 µg/kg bw) and terminated 1 d later. Bottom left panel is from a representative AhR WT mouse and bottom right panel is from a representative AhR KO mouse.",
    "ncbi_link": "GFP: 
Tomato: 
AhR: 11622
CDX2: 1045
Cre: 2777477
ER: 2099
Lgr5: 14160"
  },
  {
    "caption": "(E) Induced Cyp1a1 mRNA expression in stem cells after oral gavage with TCDD (n=4).",
    "ncbi_link": "Cyp1a1: 13076"
  },
  {
    "caption": "Flow cytometry analysis of GFP+Tomato+ and Tomato+ cells in the large intestine of AhR wild type and AhR knock out mice. (G) Quantitative analysis of the percentage of Lgr5+ stem cells in (D), n=7-10 mice per group.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(A) Representative flow cytometry gating and fluorescence microscopy images of sorted GFPhigh stem cells and GFPlow progenitor cells from Lgr5-EGFP-IRES-CreERT2 mice.",
    "ncbi_link": "EGFP: 
Cre: 2777477
ER: 2099
Lgr5: 14160"
  },
  {
    "caption": "(B) Representative brightfield images of organoids generated from GFPhigh stem cells isolated from tamoxifen treated AhR WT mice (Lgr5-GFPCreERT2 X CDX2P-CreERT2 [GC]) and KO mice (AhRf/f X Lgr5-GFPCreERT2 X CDX2P-CreERT2 [HGC]), treated with DMSO (control) or TCDD for 5 d. Data are from ≥4 mice, scale bar 200 µm.",
    "ncbi_link": "GFP: 
AhR: 11622
CDX2: 1045
Cre: 2777477
ER: 2099
Lgr5: 14160"
  },
  {
    "caption": "(C, D) The organoid forming efficiency (C) and diameter (D) from sorted GFPhigh stem cells in AhR WT or KO mice treated for 5 d with DMSO or TCDD (10 nM). n=4-5 mice per group in (C). Each dot represents an individual organoid and grey line indicates mean in (D). Bars with different letters are significantly different (p<0.05).",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(H, I) (H) Lgr5 expression in organoids and (I) sorted stem cells in the absence or presence of TCDD treatment (n≥3 independent samples per group).",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "(C) Heatmap comparison of the top 25 upstream regulators between AhR KO (KO/WT) and TCDD (TCDD/vehicle in WT mice) treated cells.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(A) FoxM1, Plk1, and Cdc25B mRNA expression in stem and progenitor cells with and without AhR, n=4 mice per group.",
    "ncbi_link": "AhR: 11622
Cdc25B: 12531
FoxM1: 14235
Plk1: 18817"
  },
  {
    "caption": "(B) FoxM1, Plk1, and Cdc25B mRNA expression in WT stem and progenitor cells with and without TCDD, n=3-4 mice per group.",
    "ncbi_link": "Cdc25B: 12531
FoxM1: 14235
Plk1: 18817"
  },
  {
    "caption": "Chromatin immunoprecipitation (ChIP) analysis of AhR and FoxM1 promoter interaction using WT colonic organoids treated with DMSO or TCDD, n=3 or 4 per group. A DNA fragment amplified in a gene desert on mouse chromosome 6 was used as a negative control.",
    "ncbi_link": "FoxM1: 14235"
  },
  {
    "caption": "Chromatin immunoprecipitation (ChIP) analysis of AhR and FoxM1 promoter interaction using WT and KO crypts (E) treated with DMSO or TCDD, n=3 or 4 per group.",
    "ncbi_link": "FoxM1: 14235"
  },
  {
    "caption": "(G Expression of FoxM1 and PLK1 at mRNA level, , n>=3 independent organoids per treatment.",
    "ncbi_link": "FoxM1: 14235
PLK1: 18817"
  },
  {
    "caption": "(L) Organoid expression of Lgr5 in response to FDI-6. Lgr5 expression level was dramatically suppressed by FDI-6 in a dose-dependent manner, n>=3 per treatment.",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "(A and B) Proliferating Lgr5+ stem cells marked by EdU in the distal colon from AhR WT (GT) and KO (HGT) mice. Arrowhead and star symbols denote proliferating stem cells (GFP+EdU+) and static stem cells (GFP+EdU-), respectively, during a 2 h EdU pulse, n=3 per treatment.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(C) Total number of EdU+ cells per crypt in the distal colon of AhR WT and KO (HGT) mice, n=3 mice per treatment. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(D&E) Crypt cell proliferative zone analysis in AhR WT and KO (HGT) mice, presented as the distance from the crypt base to the highest EdU+ cell divided by total crypt length. Red lines between crosses show the measurement of distance. Each symbol represents one crypt, n=3 mice per treatment, scale bar 20 µm. Grey line represents mean.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(F& AhR KO promoted cell proliferation 5 d post DSS treatment. AhR WT (AhRf/f [H], n=4) and AhR KO (AhRf/f X Villin-Cre [HV], n=4) mice were used.",
    "ncbi_link": "AhR: 11622
Cre: 2777477
Villin: 22349"
  },
  {
    "caption": "G) AhR KO promoted cell proliferation 5 d post DSS treatment. Data represent mean ± SEM, quantified as the ratio of the EdU+ area relative to the DAPI+ area using KeyenceTM software.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(H) Increased cell proliferation (EdU+ cells) observed in AhR KO vs WT organoids derived from HGC and GC mice, respectively (n=6 from 3 mice per group).",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(I) Effect of AhR KO on cell cycle S and G2-M phases (n=3 mice per group).",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(B) Representative colon images from AhR WT and AhR KO mice following AOM/DSS treatment. Scale bar, 9 mm.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(C) H&E staining of representative colon tumor sections from AhR WT and KO mice, scale bar 200 μm.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(E, F) (E) Adenoma and (F) adenocarcinoma multiplicity in AhR WT and KO mice.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(G) Tumor volume in AhR KO and WT mice. Grey line indicates mean.",
    "ncbi_link": "AhR: 11622"
  },
  {
    "caption": "(H) FoxM1 mRNA expression in normal (uninvolved) crypts adjacent to colonic tumors. Images were quantified and expressed as FoxM1 positive area per crypt (n=5 mice per group). Scale 200 µm. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "ncbi_link": "FoxM1: 14235"
  },
  {
    "caption": "(I) FoxM1 mRNA expression in colon tumors. FoxM1 mRNA ISH area was averaged per tumor on each slide (n=5 mice per group). Scale 200 µm. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "ncbi_link": "FoxM1: 14235"
  },
  {
    "caption": "(A-B) mRNA expression of human colonic stem cell markers LGR5 and OLFM4, n=5 or 6 independent human samples. Paired student t-test.",
    "ncbi_link": "LGR5: 8549
OLFM4: 10562"
  },
  {
    "caption": "(C) Representative images of LGR5 ISH in human organoids treated with DMSO or TCDD. Scale bar 50 µm.",
    "ncbi_link": "LGR5: 8549"
  },
  {
    "caption": "(I) Determination of luciferase reporter activity of human FoxM1 in SW48 and Caco2 cell lines treated with DMSO or TCDD. n=3-4 per group.",
    "ncbi_link": "FoxM1: 2305"
  },
  {
    "caption": "(J) FOXM1 and CYP1A1 mRNA expression in different AhR WT and CRISPR KO clones treated with TCDD for 1 d. C56 and C61 designate different human subjects.",
    "ncbi_link": "AhR: 196
CYP1A1: 1543
FOXM1: 2305"
  },
  {
    "caption": "(K) Validation of CRISPR KO clones was assessed by PCR amplification using primers flanking the targeted AhR exon. Subsequent sequencing revealed indels at the expected locations.",
    "ncbi_link": "AhR: 196"
  },
  {
    "caption": "(L) The association of FoxM1 and AhR mRNA expression in human normal colon biopsies (n=304). AhR low (n=152) is defined as below its median expression; AhR high (n=152) is defined as above its median expression. Dashed line indicates median and dotted lines indicate 25th/75th quartiles.",
    "ncbi_link": "AhR: 196
FoxM1: 2305"
  },
  {
    "caption": "(M) Correlation between FoxM1 and Cyp1b1 mRNA expression in human normal colon biopsies (n=303) analyzed by Spearman rank correlation.",
    "ncbi_link": "Cyp1b1: 1545
FoxM1: 2305"
  },
  {
    "caption": "(a) Ultrastructural evidence of autophagy induced by depletion of p53 with a specific siRNA or pharmacological inhibition of p53 with PFT-α in HCT116 cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(b) Autophagy induced by PFT-α, p53 knockdown, or p53 knockout in HCT116 cells. The number of autophagosomes and autolysosomes was determined for at least 50 cells in 3 independent experiments (mean ± s.e.m.; *P 0.05). Culture in nutrient-free (NF) conditions was used as a positive control.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(c) Effect of p53 on the maturation of LC3. Immunoblots are shown for wild-type (WT) or p53−/− HCT116 (n = 3).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(d) GFP-LC3 puncta induced by PFT-α, p53 knockdown or knockout. WT and p53−/− HCT116 cells were transfected with control or p53-specific siRNAs, re-transfected with a GFP-LC3 plasmid, cultured in complete medium for 24 h and kept for 6 h in the presence or absence of 30 μM PFT-α. The percentage of cells showing accumulation of GFP-LC3 in puncta (GFP-LC3vac) is reported (mean ± s.d., n = 3; *P 0.05).",
    "ncbi_link": "LC3: 440738///81631///84557
p53: 7157"
  },
  {
    "caption": "(e) GFP-LC3 puncta in p53−/− MEF, compared with WT MEF transfected with GFP-LC3 (mean ± s.d., n = 3; *P 0.05).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(f) GFP-LC3 dots in tissues from p53+/+ or p53−/− mice expressing a GFP-LC3 transgene (mean ± s.d.; *P 0.05), without or after 24 h of starvation. The number of GFP-LC3 dots per area was determined for a minimum of 4 fields (at ×400 magnification for 4 slides per animal, 3 animals per condition).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(g) TEM pictures of p53−/− and p53+/− mouse livers. p53−/− hepatocytes carry approximately 3 autophagosomes, p53+/− controls approximately 1 per cell.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(h) Modulation of DsRed::LGG-1 levels by the p53 orthologue CEP-1 in C. elegans. Representative pictures are shown for WT animals and for nematodes carrying a cep-1 deletion allele (gk138). The count of puncta per cell was 6.9 ± 3.3 for WT, 52.2 ± 9.4 for cep-1 (gk138) embryos (mean ± s.e.m. for 20 individuals, 5 cells per embryo). The quantification of DsRed::LGG-1 puncta is shown for the indicated genetic backgrounds and conditions (dots represent pixel intensity for individual embryos).",
    "ncbi_link": "cep-1: 172616
CEP-1: 172616"
  },
  {
    "caption": "(a) PFT-α or p53 siRNA-induced GFP-LC3 puncta in WT HCT116 cells transfected with siRNAs to deplete the essential autophagy gene products Atg5, Atg10, Atg12, Beclin 1 or hVps34. Culture in nutrient-free (NF) conditions was used as a control of autophagy induction.",
    "ncbi_link": "Atg10: 83734
Atg12: 9140
Atg5: 9474
Beclin 1: 8678
hVps34: 5289
p53: 7157"
  },
  {
    "caption": "(b) PFT-α or p53 siRNA-mediated GFP-LC3 puncta in MEFs transfected with siRNAs specific for mouse Atg5 or Beclin 1.",
    "ncbi_link": "Atg5: 11793
Beclin 1: 56208
p53: 22059"
  },
  {
    "caption": "(c) Requirement of Beclin 1 expression for autophagy induction by p53 depletion in MCF7 cells. MCF7 cells stably transfected with a tetracycline-repressible Beclin 1 construct were maintained in conditions that prevent or allow Beclin 1 expression, transfected with GFP-LC3 and subjected to p53 knockdown before quantification of GFP-LC3 puncta. Data in a-c are mean ± s.d. of 3 independent experiments.",
    "ncbi_link": "Beclin 1: 8678
p53: 7157"
  },
  {
    "caption": "(a) Immunoblot detection of the phosphorylation status of AMPKα, ACCα, TSC2 and p70S6K in HCT116 cells. Hypophosphorylation of p70S6K and hyperphosphorylation of AMPKα, ACCα and TSC2 was detected in p53−/− HCT116, compared with WT HCT116 cells after culture in complete medium (n = 5).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(b) Quantification of GFP-LC3vac cells in WT and p53−/− HCT116 cells transfected with siRNAs specific for the catalytic α1 and α2 subunits of AMPK (mean ± s.d. of 3 independent experiments; *P 0.05). The inset in b demonstrates the efficiency of siRNA-mediated downregulation of AMPKα1 and AMPKα2 , as assessed by immunoblot analysis (n = 3). Note that the antibody recognizes both AMPKα1 and AMPKα2.",
    "ncbi_link": "AMPKα1: 5562
AMPKα2: 5563
p53: 7157"
  },
  {
    "caption": "(c) Immunoblot detection of ACCα phosphorylation in WT and p53−/− HCT116 cells subjected to knockdown of AMPKα1 and AMPKα2 (n = 5); Co, control.",
    "ncbi_link": "AMPKα1: 5562
AMPKα2: 5563
p53: 7157"
  },
  {
    "caption": "(d) Quantification of GFP-LC3vac cells (means ± s.d., n = 3 separate experiments) in WT HCT116 and p53−/− HCT116 treated with PFT-α and/or rapamycin.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(a) Cytosolic ATP levels in WT and p53−/− HCT116 cells in the absence of glucose. Measurements were performed on luciferase-expressing HCT116, after perfusion of the cells with medium first containing then missing glucose.",
    "ncbi_link": "luciferase: 
p53: 7157"
  },
  {
    "caption": "(b) Effect of methylpyruvate (MetPyr) on ATP levels in WT p53−/− HCT116 cells depleted of glucose. ATP levels were measured as in a, in the presence of glucose and 15 min after its withdrawal or replacement by MetPyr.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(c) Effect of autophagy on the ATP levels of WT and p53−/− HCT116 cells depleted of glucose. Cells were transfected with siRNAs specific for Beclin 1 and AMPKα, or they were treated with rapamycin for 6 h, followed by measurement of ATP levels as in a, before or after glucose withdrawal (means ± s.d. of triplicates, 3 independent experiments).",
    "ncbi_link": "Beclin 1: 8678
AMPKα: 5563///5562
p53: 7157"
  },
  {
    "caption": "(d) Metabolic stress-induced cell death is attenuated in the absence of p53. HCT116 cells were transfected with control, Atg5-, Atg10-, or AMPKα-specific siRNAs and were subjected 48 h later to metabolic stress (cultured for 48 h in nutrient-free, hypoxic conditions) and stained with DiOC6(3) and PI. The black and white portions of the columns refer to the DiOC6(3)low PI− (dying) and DiOC6(3)low PI+(dead) population, respectively.",
    "ncbi_link": "Atg10: 83734
Atg5: 9474
AMPKα: 5563///5562
p53: 7157"
  },
  {
    "caption": "(e) Metabolic stress-induced decrease of clonogenic survival was attenuated in the absence of p53. HCT116 cells subjected to metabolic stress as in d were monitored for clonogenic survival.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(f) Expression of Beclin 1 in MCF7 cells restores the survival advantage conferred by p53 depletion. MCF7 cells that carry a tetracycline-repressible Beclin 1 expression construct were cultured to avoid Beclin 1 expression or to induce it, transfected with a control siRNA or a p53-specific siRNA, subjected to metabolic stress, and finally stained with DiOC6(3)/PI.",
    "ncbi_link": "Beclin 1: 8678
p53: 7157"
  },
  {
    "caption": "(g) Effect of p53 and autophagy on the survival of metabolically stressed MEFs. WT MEFs were transfected with the indicated siRNAs and then subjected to metabolic stress before performing clonogenic assays. Results in d-g are mean ± s.d. of 3 separate experiments (*P 0.05); Co, control.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(c-e) Effect of p53 mutants on autophagy in p53−/− HCT116 cells.Representative micrographs of cells transfected with plasmids expressing WT, nuclear and cytoplasmic p53 are shown in d",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(c-e) Effect of p53 mutants on autophagy in p53−/− HCT116 cells. Quantification of GFP-LC3 puncta of p53−/− HCT116 cells transiently transfected with p53 mutants is shown in e (mean ± s.d., n = 3 experiments, *P 0.05)",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(f) Detection of the phosphorylation status of AMPKα, ACCα, TSC2 and p70S6K in p53−/− HCT116 cells transiently expressing WT or mutant p53 (n = 5).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(d) eIF2α phosphorylation in WT or p53−/− HCT116 cells treated with PFT-α (n = 5).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(e, f) WT HCT116 cells (e, f) or p53−/− HCT116 cells (f) were transfected with GFP-LC3, plus a control siRNA or the indicated combination of IRE1α- and/or p53-specific siRNA, and treated with PFT-α, thapsigargin, tunicamycin or brefeldin A.",
    "ncbi_link": "IRE1α: 2081
p53: 7157"
  },
  {
    "caption": "(g) GFP-LC3-transfected WT or ire1α−/− MEF were treated with PFT-α. Columns in e-g show means ± s.d. of 3 independent experiments (*P 0.05).",
    "ncbi_link": "ire1α: 78943"
  },
  {
    "caption": "(c) WT HCT116 cells transfected with control or HDM2-targeted siRNAs were cultured in the presence or absence of MG132 for 3 h, followed by the treatment with autophagy inducers for 6 h (Tp, thapsigargin; other abbreviations as in b). The abundance of p53 and HDM2 was determined by immunoblotting analysis and the percentage of cells showing accumulation of GFP-LC3 in vacuoles (GFP-LC3vac) was determined.",
    "ncbi_link": "HDM2: 4193"
  },
  {
    "caption": "(e) Effect of MG132 and HDM2 siRNA on autophagy of WT and p53−/− HCT116 cells.",
    "ncbi_link": "HDM2: 4193
p53: 7157"
  },
  {
    "caption": "(f) Failure of HDM2 inhibitors to prevent autophagy induced by the absence of p53. Nutlin-3 and RITA were added to p53−/− HCT116 cells, followed by quantification of GFP-LC3 puncta.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(g) Effect of WT and ubiquitination-resistant p53 on autophagy. p53−/− HCT116 cells were transfected with GFP-LC3 alone or in combination with different concentrations of pcDNA3.1, WT p53 or p53 lacking the ubiquitination site at amino acids 13-19 (p53ΔI), then treated with rapamycin, tunicamycin or thapsigargin. Thereafter, p53 expression and GFP-LC3 puncta were quantified.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(h) Depletion of Atg5 or Beclin 1 does not prevent p53 degradation triggered by rapamycin or ER stressors. In WT HCT116 cells transfected with siRNA targeting Atg5 or Beclin 1, p53 levels were determined by immunoblot analysis after 6 h of treatment with rapamycin, tunicamycin or thapsigargin.",
    "ncbi_link": "Atg5: 9474
Beclin 1: 8678"
  },
  {
    "caption": "C TIMM50S levels in primary and immortalized skin fibroblast from control (C1-4) and mutant TIMM50 (Pt). SDHA and ETHE1 are shown as loading controls.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "D qPCR quantification of TIMM50 transcript levels in control and TIMM50 mutant fibroblasts. Data are shown as mean ± SD, n = 4.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "A Western-blot of whole cell extracts for different components of the protein import machinery in control and TIMM50 mutant fibroblasts grown in either glucose or galactose containing medium.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "B Western-blot of whole cell extracts for different components of the protein import machinery in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in either glucose or galactose containing medium.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "D TMRM live staining of control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in either glucose or galactose containing medium. Scale bar corresponds to 10 μm.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "A In organello import of the precursors of TFAM and AAC1 into isolated mitochondria from control and TIMM50 mutant fibroblasts in the absence or presence of the uncoupler FCCP. The radiolabeled precursors were incubated with isolated mitochondria for the indicated times followed by trypsin treatment only in the case of AAC1. Coomassie Blue (CB) staining was used as loading control and the radiolabeled protein (TNT) as reference for quantification. The position of the precursor (empty arrowheads) and the mature protein (filled arrowhead) are also shown. Western blot for TIMM50 is shown as cell line control. B Quantification of TFAM and AAC1 import from control and TIMM50 mutant fibroblasts expressed as fraction of the input radiolabeled precursor converted into mature protein and normalized to Coomassie Blue signal. Data are shown as mean ± SD, n = 3 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001 grouping both controls together. ",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "C In organello import of the precursors of TFAM and AAC1 into isolated mitochondria from control and TIMM50 mutant fibroblasts transduced with the empty vector (EV) or with wild-type TIMM50 in the absence or presence of the uncoupler FCCP The position of the precursor (empty arrowheads) and the mature protein (filled arrowhead) are also shown. D Quantification of TFAM and AAC1 import from control and TIMM50 mutant fibroblasts transduced with the empty vector (EV) or with wild-type TIMM50 expressed as fraction of the input radiolabeled precursor converted into mature protein and normalized to Coomassie Blue signal. Data are shown as mean ± SD, n = 3 biological replicates; ∗p < 0.05. ",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "Western blot for representatives of all five respiratory complexes in control and TIMM50 mutant fibroblasts grown in glucose or galactose. Two biological replicates are shown for each cell line and condition. Significant changes in protein levels in TIMM50 mutant fibroblasts compared to controls have been boxed in red.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "B Western blot for representatives of all five respiratory complexes in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Two biological replicates were obtained for each cell line and condition. Significant changes in protein levels in TIMM50 mutant fibroblasts complemented with TIMM50 compared to EV have been boxed in red.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "Oxygen consumption measurements in control and TIMM50 mutant fibroblasts grown in glucose or galactose. Values of basal and maximal respiration along with ATP-production dependent, proton leak respiration and spare capacity are shown. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001 grouping both controls together.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "D Oxygen consumption measurements in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Values of basal and maximal respiration along with ATP-production dependent, proton leak respiration and spare capacity are shown. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "A ROS production as measured by intracellular oxidation of the cell-permeant probe DCF-DA in control and TIMM50 mutant fibroblasts grown in glucose or galactose. Measurements were made in untreated cells and after treatment with 250μM hydrogen peroxide for 30 min. Data are shown as mean ± SD, n = 3 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001 grouping both controls together.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "B Steady state levels of ROS related proteins SOD2 and ACO2 in control and TIMM50 mutant fibroblasts growing in either glucose or galactose were assessed by Western blot using GAPDH as internal control. C Quantification of the steady state levels of SOD2 and ACO2 in control and TIMM50 mutant fibroblasts growing in either glucose or galactose. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01 grouping both controls together.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "D Steady state levels of mitophagy related proteins VDAC1, p62 and LC3-II in control and TIMM50 mutant fibroblasts growing in either glucose or galactose were assessed by Western blot using GAPDH as internal control. E Quantification of the steady state levels of VDAC1, p62 and LC3-II in control and TIMM50 mutant fibroblasts growing in either glucose or galactose. Data are shown as mean ± SD, n = 4 biological replicates; ∗∗p < 0.01, ∗*∗p < 0.001 grouping both controls together.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "A Cell size in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Data are shown as mean ± SD, n = 5 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "B Growth curves of control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Cell growth was monitored continuously by the Incucyte live cell imager (Essen Bioscience). One of the three independent experiments carried out is presented. Data are shown as mean of three technical replicates ± SD.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "C Plot of Annexin V intensity against propidium iodine signal in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Cells in the late stage of apoptosis are boxed in the top right corner.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "D Quantification of the number of late apoptotic cells in control and TIMM50 mutant fibroblasts, transduced with the empty vector (EV) or with wild-type TIMM50 grown in glucose or galactose. Data are shown as mean ± SD, n = 5 or 4 biological replicates in the case of transduced cells; ∗*∗p < 0.001.",
    "ncbi_link": "TIMM50: 92609"
  },
  {
    "caption": "A Western-blot of whole cell extracts for TIMM50 and GAPDH in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts grown in either glucose or galactose containing medium.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "B Mitochondrial membrane potential in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts grown in glucose or galactose using JC-1 staining in untreated or FCCP treated conditions. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "C Western blot for representatives of all five respiratory complexes in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts grown in glucose or galactose. GAPDH is from the same blot as panel A. Quantification based on two biological replicates for RNASEH1 and ISCU mutant fibroblasts Significant changes in protein levels in RNASEH1 and ISCU mutant fibroblasts compared to controls have been boxed in red.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "D Oxygen consumption measurements in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts grown in glucose or galactose. Values of basal and maximal respiration along with ATP-production dependent, proton leak respiration and spare capacity are shown. Data are shown as mean ± SD, n = 4 biological replicates; ∗p < 0.05, ∗∗p < 0.01, ∗*∗p < 0.001.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "E Steady state levels of ROS related proteins SOD2 and ACO2 and mitophagy related proteins VDAC1, p62 and LC3 in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts growing in either glucose or galactose were assessed by Western blot using GAPDH as internal control. GAPDH is from the same blot as panel A.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "F Quantification of the number of late apoptotic cells in control and TIMM50, RNASEH1 and ISCU mutant fibroblasts grown in glucose or galactose. Data are shown as mean ± SD, n = 4 or more biological replicates; ∗*∗p < 0.001.",
    "ncbi_link": "ISCU: 23479
RNASEH1: 246243
TIMM50: 92609"
  },
  {
    "caption": "A The mRNA value of AKT2 was analyzed in the GEO Profiles from the  liver explant of  Hepatitis B virus (HBV)-associated acute liver failure (ALF) patients (GDS4387/225471_s_at), and from bronchial epithelial cells  with pandemic and seasonal H1N1 influenza virus infections in vitro (GDS4855/203808_at). normal, n=10; HBV, n=17; control, n=3; influenza A, n=9. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using unpaired t-test Error bars mean ± SD",
    "ncbi_link": "AKT2: 208"
  },
  {
    "caption": "C The  qRT-PCR  analysis of Akt2  mRNA in PEMs  stimulated with  lipo-poly(I:C) (1 μg/mL), lipo-poly(A:T) (1 μg/mL),  lipo-ISD  (3 μg/mL) or HSV-1 (MOI, 1) for 6 hours. n=3, respectively. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using one-way ANOVA test Data are from three independent biological replicates Error bars mean ± SEM).",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "D The mRNA of Akt2  (red line) and Ifnb1 (black line) were analyzed by qRT-PC  in the mock and VSV  (MOI, 1) or LM (MOI, 1)-stimulated PEMs  or BMDMs at the indicated  time. Mock and VSV, n=4; mock and  LM, n≥3.",
    "ncbi_link": "Akt2: 11652
Ifnb1: 15977"
  },
  {
    "caption": "G-H PEMs  were pretreated with DMSO or AKT2  inhibitor CCT128930  (10 μM) (G) for 2 hours, or knocked down of  Akt2 with siAkt2-1 (20 nM) for 48 hours (H), then the mRNA level of Ifnb1  was measured by  qRT-PCR after lipo-poly(I:C),  lipo-poly(A:T), lipo-ISD, VSV, or HSV-1  stimulation for another 6 hours. n=3, respectively. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using two-way ANOVA test Data are from three independent biological replicates Error bars mean ± SEM).",
    "ncbi_link": "Akt2: 11652
Ifnb1: 15977"
  },
  {
    "caption": "A-B qRT-PCR detection for the mRNA  expression  of Ifnb1 (A), Ifna4, Cxcl10  and Ccl5 (B) in WT (n=3) and Akt2  KO (n=3)  PEMs stimulated with lipo-poly(I:C), VSV,  lipo-poly(A:T), lipo-ISD or HSV-1 for 6 hours. C The  expression  of Ifnb1 mRNA level by  qRT-PCR  in WT (n=3) and Akt2 KO (n=3)  PEMs treated with poly(I:C) (10 μg/mL) for 6 hours (left panel) or LPS  (1 μg/mL) for 2 hours (right panel). Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using two-way ANOVA test Data are from three independent experiments Error bars mean ± SEM",
    "ncbi_link": "Akt2: 11652
Ccl5: 20304
Cxcl10: 15945
Ifna4: 15967
Ifnb1: 15977"
  },
  {
    "caption": "H  Zebrafish larvae were overexpressed the indicated protein for 48 hours and challenged with VSV for another 6 hours, then the mRNA levels of  ifn1 in zebrafish larvae were measured by qRT-PCR (left panel). Every dot represents three  zebrafish embryos. Horizontal square bracket shows the statistical analysis of the comparison with 'PBS mock', the rest shows the comparison with 'PBS VSV'. PBS mock, n=5;  PBS VSV, n=13; AKT2 VSV, n=7; AKT2-T309A/S474A  VSV, n=9. H&E staining (middle panel) and survival rates (Kaplan-Meier curve) (right panel) were collected from  zebrafish larvae after  VSV micro-injection for 18 hours or longer. The arrows indicated the  VSV-infected eye  and  skeletal muscle in  zebrafish larvae. Bars, 100 μm. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using a one-way ANOVA test or log-rank (Mantel-Cox) test Data are from three independent biological replicates Error bars mean ± SD).",
    "ncbi_link": "AKT2: 378972
ifn1: 360134"
  },
  {
    "caption": "D WT and  Akt2  KO  PEMs were infected with or without VSV for 6 hours. Then, cell lysates of WT or  Akt2 KO  PEMs were prepared for immunoprecipitation  using anti-AKT2  antibody, followed by  immunoblotting  using anti-IRF3 antibody (left panel). Alternatively, cell lysates were prepared for immunoprecipitation  using anti-IRF3 antibody, followed by immunoblotting using anti-AKT2  antibody (right panel) to detect the endogenous interaction between AKT2 and IRF3. Data information: * Data are representative of two or three independent biological replicates",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "G Immunofluorescent  microscopic imaging for (left panel) and statistics analysis (right panel) for IRF3 nuclear translocation in WT and Akt2 KO PEMs at 6 hour post-VSV  infection. IRF3 (red), Nuclei  (Hoechst, green). The white arrows indicate the nuclei  with IRF3 translocation. Mock, n=2; VSV, n=3. Bar, 20 μm. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using two-way ANOVA test Data are representative of two or three independent biological replicates Error bars mean ± SEM).",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "H Immunoassay of  IRF3, AKT2, LaminB1  and GAPDH  in the  nuclear and cytoplasmic fractions from the WT and Akt2  KO PEMs after VSV treatment for 6 hours.  Tubulin  and  LaminB1 were used as cytoplasmic  and nucleic protein loading control respectively. Data information: * Data are representative of two or three independent biological replicates",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "D  Immunofluorescence microscopy (top panel) of  AKT2-,  Flag-IRF3- or  Flag-IRF3-T207A-overexpressed  MEF cells after  poly(A:T) stimulation for 6 hours. Flag (IRF3, red) and Hoechst (nuclei, blue). Immunoassay  of nuclear-cytoplasm extractions (bottom panel) from  HEK293T-IRF3 KO cells with overexpression of the indicated plasmids for 24 hours followed by  VSV  infection for 6 hours.  GAPDH  and  SP1  were used as cytoplasmic  and nucleic protein loading control respectively. Bar, 20 μm. Data information: * Data are representative of three independent experiments",
    "ncbi_link": "Flag: 
AKT2: 208
IRF3: 3661"
  },
  {
    "caption": "G qRT-PCR analysis of the  VSV  copies in overexpressed zebrafish embryos with the VSV  challenge at 18 hours later. Every dot represents three zebrafish embryos. Horizontal vertical square bracket shows the statistical analysis of comparison with 'PBS  mock', the rest shows the comparison with 'PBS VSV'. PBS mock, n=15; PBS VSV, n=9; IRF3 VSV, n=16; IRF3-T207A VSV, n=11; AKT2 VSV, n=14; AKT2-T309A/S474A VSV, n=9; IRF3 + AKT2 VSV, n=9; IRF3 + AKT2-T309A/S474A VSV, n=13; IRF3-T207A + AKT2 VSV, n=10. Data information: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and ns, not significant (P > 0.05); using a one-way ANOVA test Data are representative of three independent experiments Error bars mean ± SD).",
    "ncbi_link": "AKT2: 378972
IRF3: 564854"
  },
  {
    "caption": "B  Survival  rates of WT and Akt2 KO  mice after lethal dose injection of VSV  during 120 hours (1 × 107 PFU/g, i.v.). Data information: *P < 0.05, **P < 0.01; using a log-rank (Mantel-Cox) test Data are representative of three independent experiments respectively",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "E WT and  Akt2  KO mice were injected with VSV  for 24 hours (1 × 106 PFU/g, i.v.). Representative images of the  VSV infected cells (GFP) were collected by fluorescence microscope (left panel) and the VSV  copies (WT, n=6; Akt2 KO n=7) were measured by qRT-PCR (right panel) in the liver of mice. Bar, 100 μm. Data information: *P < 0.05, **P < 0.01; using a unpaired t-test Data are representative of three independent experiments respectively in which the different groups of mice were sacrificed and quantified for indicated experimental purposes Error bars mean ± SD).",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "Bone marrow cells  from WT and Akt2 KO mice  (CD45.2) were adoptively transferred to lethally irradiated CD45.1 mice  and infected with VSV. representative images were analyzed Data information: * Data are representative of three independent experiments respectively",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "immunoblot  analysis of  IRF3,  LaminB1 and GAPDH in the PIC  nuclear  and cytoplasmic fractions (C) from WT and Akt2 KO mice  treated with TMPD  for 2 weeks. GAPDH and LaminB1 were used as cytoplasmic and  nucleic protein loading control respectively. Data information: * Data are representative of three independent experiments",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "H&E-staining  (E left panel) and immunofluorescence of IgG  deposits (E right panel) in the kidney  sections were collected from WT and Akt2  KO bone marrow-reconstituted  CD45.1 mice Bar, 50 μm. Data information: * Data are representative of three independent experiments",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "J. qRT-PCR analysis of the relative mRNA  expression levels of AKT2 (left panel) and IFNA  (middle panel) or  IFNβ1 (right panel) in CD14  positive monocytes isolated from SLE patients  (n=9) or healthy donors (n=9). Data information: *P < 0.05, **P < 0.01 and ****P < 0.0001; using unpaired t-test or correlation analyses Data are pooled from different individuals Error bars mean ± SD).",
    "ncbi_link": "AKT2: 208
IFNA: 3439///3443///3451///3452///3447///3446///3441///3448///3444///3445
IFNβ1: 3456"
  },
  {
    "caption": "The protein levels of CD14  and CD301  in CD301- macrophages  and CD301+ macrophages  examined by western blot (n=3 technical replicates for each group). Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "ncbi_link": "CD301: 10462"
  },
  {
    "caption": "The protein levels of Fibronectin, Collagen 1, α-SMA  and CTGF  expression in primary human endometrial stromal cells (hESCs) treated by the supernatants of CD301- and CD301+ macrophages  for 48h, respectively examined by  western blot (n=3 technical replicates for each group). Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "ncbi_link": "CD301: 10462"
  },
  {
    "caption": "The protein levels of GAS6  and CCL8 expression  in sorted human endometrial CD301- and CD301+ macrophages  (n=3 technical replicates for each group). Data are presented as mean ± SEM. Two-tailed Student's t-test. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "ncbi_link": "CD301: 10462"
  },
  {
    "caption": "Western blot  analysis of α-SMA  and Collagen 1  in hESCs  treated with Bemcentinib  (1μM) for 1 hour, followed by GAS6  (50ng/mL) for 72h (n=3 technical replicates for each group). Western blot  analysis of α-SMA and Collagen 1 in hESCs  treated with the supernatants of CD301- and CD301+ macrophages  and GAS6  neutralizing antibody (2.5μg/mL) for 72h (n=3 technical replicates for each group). Data are presented as mean ± SEM. One-way ANOVA with Tukey's post hoc analysis. *, P<0.05; **, P<0.01; ***, P<0.001. NS, not significant.",
    "ncbi_link": "CD301: 10462"
  },
  {
    "caption": "qRT-PCR analysis of ACTA2  and COL1A1  expression in hESCs  treated with GAS6  (50ng/mL) or JSH23  (10μM) for 72h (n=3 biological replicates for each group). Data are presented as mean ± SEM. One-way ANOVA with Tukey's post hoc analysis. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277"
  },
  {
    "caption": "qRT-PCR analysis of Acta2  and Col1a1  expression in the uterus  of Sham, IUA  and IUA+DT mice  (n=5 mice  for each group). Data are presented as mean ± SEM. One-way ANOVA with Tukey's post hoc analysis. *, P<0.05; **, P<0.01; ***, P<0.001.",
    "ncbi_link": "Acta2: 11475
Col1a1: 12842"
  },
  {
    "caption": "qRT-PCR analysis of Acta2  and Col1a1  expression in the uterus  of IUA+PBS  and IUA+BEM mice  (n=5 mice  for each group). Data are presented as mean ± SEM. (B, Two-tailed Student's t-test.",
    "ncbi_link": "Acta2: 11475
Col1a1: 12842"
  },
  {
    "caption": "SARS-CoV-2.For weigh loss record, hACE2 mice (n=7) and WT mice (n=3) were experimentally challenged intranasally with SARS-CoV-2, and the ACE2-Mock mice (n=3) were used as control. And then the weight loss was recorded over 14 days (a, ANOVA, ***p<0.001).",
    "ncbi_link": "ACE2: 59272
hACE2: 59272"
  },
  {
    "caption": "To screen virus replication, 12 mice were infected in each group, and 3 mice per group were sacrificed and their major organs harvested for viral load and virus titer at 1 dpi, 3 dpi, 5 dpi and 7 dpi respectively. The distribution of SARS-CoV-2 in the primary organs of ACE2-HB-01 mice was detected by qRT-PCR (b).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "the virus isolated from lungs of ACE2-HB-01 mice at 3 dpi was observed by electron microscope (d).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "mice.a. Gross pathology and histopathology of lungs from WT-HB-01 mice (3 dpi), ACE2-Mock mice (3 dpi) and ACE2-HB-01 mice (3 dpi and 5 dpi). Postmortem examinations showed focal dark red lesions (red arrow) throughout the dorsal of the right middle lobe of the lung at 3dpi. The lesions progressed into multifocally scattered-dark reddish purple areas and palpable nodules (red arrow) throughout the right lobe of the lung at 5 dpi. Histopathological observation indicated that moderate interstitial pneumonia with thickened alveolar septa (black arrows) and infiltration of lymphocytes (red arrows). The swollen and degenerative alveolar macrophages (green arrows) are scattered within the alveolar cavities at 3dpi and 5 dpi.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " Immunofluorescence analysis of viral antigens in lungs of SARS-CoV-2-infected hACE2 mice.Co-localization of SARS-CoV-2 S protein and hACE2 receptor in hACE2 mouse lungs, the sections were incubated with anti-SARS-CoV-2 S protein antibody, anti-human ACE2 antibody, and DAPI. The lung sections of ACE2-Mock mice (a-d). The lung sections of ACE2-HB-01 mice (e-h). The white arrows showed the viral S protein (f) and hACE2 (g), respectively, the yellow arrow showed the merge of viral S protein and hACE2 (h). White bar=25 µm. ",
    "ncbi_link": "ACE2: 59272
hACE2: 59272"
  },
  {
    "caption": "(A) Relative values (RV) of p62 mRNA level in frontal lobe of SIVE versus SIV and uninfected (UN) monkeys, n = 7 for SIVE, n = 12 for SIV and n = 9 for UN, P<0.05.",
    "ncbi_link": "p62: 712783"
  },
  {
    "caption": "B) RV of p62 mRNA level in frontal cortex of HAD versus non neurological diseased subjects (NNDS), n = 8 for HAD and n = 10 for NNDS, P<0.0001.",
    "ncbi_link": "p62: 51164"
  },
  {
    "caption": "A Representative pictures of embryos at 18.5 days postcoitum (E18.5) and hematoxylin and eosin staining of whole-mount embryo sections from PR-SET7loxp/Alfp-Cre (PR-SET7ΔHepE) mice and control littermates (WT).",
    "ncbi_link": "Alfp: 
Cre: 
PR-SET7: 67956"
  },
  {
    "caption": "D qPCR analysis of Albumin,Afp and HNF4 mRNA levels. Bars represent mean values of mRNA levels normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA and SEM from samples of four individual mice. *P-value < 0.01.",
    "ncbi_link": "GAPDH: 
Afp: 11576
Albumin: 11657
HNF4: 15378"
  },
  {
    "caption": "A Macroscopic appearance of livers in 120-day-old (P120) wild-type (WT) and PR-SET7loxp/Alb-Cre (KO) mice. Note, small adenomatous foci in KO livers.",
    "ncbi_link": "Alb: 
Cre: 
PR-SET7: 67956"
  },
  {
    "caption": "B Representative hematoxylin and eosin staining of liver sections from P120 wild-type (WT) and PR-SET7loxp/Alb-Cre (PR-SET7ΔHepA) mice. Arrows show three areas containing morphologically different hepatocytes. Right panels: zoom-in to Area-A-'normal zone', to Area-B-'necrotic zone' and to Area-C-'regenerative zone'.",
    "ncbi_link": "Alb: 
Cre: 
PR-SET7: 67956"
  },
  {
    "caption": "C Immunohistological staining of liver sections from P120 PR-SET7ΔHepA mice and control littermates (WT) with HNF4 antibody.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "D TUNEL staining of liver sections from P120 PR-SET7ΔHepA mice and control littermates (WT). Note that cells containing enlarged nuclei (white arrows) are TUNEL negative.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "A Electronmicroscopic images of cells containing enlarged nuclei in P120 PR-SET7ΔHepA livers and normal hepatocytes in control littermates (WT). White arrows indicate: (Nuc) nuclei; (ER) endoplasmic reticulum; (Mit) mitochondrium; (PM) plasma membrane; (a) swollen mitochondria; (b) swollen endoplasmic reticulum; (c) disorganized endoplasmic reticulum; (d) disrupted plasma membrane; and (e) disorganized pieces of endoplasmic reticulum encircling mitochondria to form autophagosomes.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "B Immunohistological staining of liver sections from P120 PR-SET7ΔHepA mice and control littermates (WT) with H4K20Me1 and H4K20Me3 antibodies. Normal (Area-A), Necrotic (Area-B) and Regenerative (Area-C) hepatocyte-containing areas are indicated. Arrows show the loss of H4K20Me1 signal from the large necrotic nuclei.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "C-F Partial (2/3rd) hepatectomy was performed in 45-day-old PR-SET7ΔHepA mice and control littermates (WT). Two weeks later, at postnatal day 60 (P60) liver sections were stained with hematoxylin and eosin (C) or γH2AX (D) or H4K20Me1 (E) or HNF4 and F4/80 (F) antibodies.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "A, B Immunohistological staining of liver sections from P120 PR-SET7ΔHepA mice and control littermates (WT) with Ki67, albumin (Alb) and A6 or HNF4 antibodies as indicated. Arrows depict the different areas in the sections as indicated above (Fig.1B). Asterisks (*) indicate Ki67+ hepatocytes. Small arrows (>) indicate Ki67+ non-hepatic cells. Note the lack of co-staining of cells with HNF4 and A6 antibodies.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "C Immunohistological staining of liver sections from P120 PR-SET7ΔHepA mice and control littermates (WT) with FGF7 and A6 antibodies.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "D Relative mRNA levels of FGF7. Bars represent mean FGF7 mRNA levels normalized to GAPDH mRNA and SEM from samples of 5 individual 45 days or 120-day-old mice. The data are presented as fold over values obtained with wild-type P45 samples. *P-value < 0.01.",
    "ncbi_link": "GAPDH: 
FGF7: 14178"
  },
  {
    "caption": "A Analysis of reactive oxygen species (ROS) accumulation in frozen liver sections from 120-day-old (P120) and 240-day-old (P240) PR-SET7ΔHepA mice and control littermates (WT).",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "D Macroscopic appearance of livers in P240 PR-SET7ΔHepA mice and control littermates (WT).",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "F Representative hematoxylin and eosin staining of liver sections from P240 PR-SET7ΔHepA mice and control littermates (WT). Two different magnifications are shown.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "G Relative mRNA levels of selected oncofetal genes. Bars represent mean Afp, H19, GPC-3 and CTGF mRNA levels normalized to GAPDH mRNA and SEM from samples of 5 individual 240-day-old mice. The data are presented as fold over values obtained with wild-type samples. *P-value < 0.01.",
    "ncbi_link": "GAPDH: 
Afp: 11576
CTGF: 14219
GPC-3: 14734
H19: 14955"
  },
  {
    "caption": "A, B Immunohistological staining of liver sections from P240 PR-SET7ΔHepA mice and control littermates (WT) with Afp and HNF4 (A) or Ki-67 and albumin (Alb) (B) antibodies.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "C-E Double staining of liver sections with A6 and HNF4 (C) or Sox9 and Alb (D) or CD133 and HNF4 (E) antibodies. Right panels show larger magnifications of stainings performed in PR-SET7ΔHepA liver sections.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "A P240 PR-SET7ΔHepA liver sections were double-stained with A6 and Sox9 (upper panel) or CD133 and Sox9 (lower panel). Pie charts at the right represent average percentages of cells stained positively with the indicated markers after counting DAPI-stained cells in 5 high-power fields (HPF) in liver sections of 3 different mice.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "B Cell duplication rate of primary hepatocytes from P240 PR-SET7ΔHepA livers in culture.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "C Pictures of representative subcutaneous xenograft tumors dissected from immunodeficient mice 20 days after injection with primary hepatocytes from P240 PR-SET7ΔHepA livers or Hepa 1-6 cells. Right panel shows average tumor volumes (n = 3) dissected at the indicated time points following injection.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "D, E Hematoxylin and eosin and immunohistological staining with A6, HNF4, Sox9 and CD133 antibodies of tumor sections from xenografts dissected 20 or 30 days after injection with primary hepatocytes from P240 PR-SET7ΔHepA livers.",
    "ncbi_link": "PR-SET7: 67956"
  },
  {
    "caption": "A CD81 knockout of 293T cells. The knockout cell line was generated by CRISPR-Cas9. The immunoblots using CD81 antibody and actin antibody were conducted on the same film.",
    "ncbi_link": "Cas9: 
CD81: 975"
  },
  {
    "caption": "B CD81 facilitates CD19 maturation. CD81 and CD19 (300 ng DNA) were transfected into the CD81-knockout 293T cells. Anti-FLAG immunoblot was performed for CD19 with a C-FLAG tag. The deglycosylation was performed by digesting the cell lysate with PNGase F or Endo H, following the manufacturers' instructions. The deglycosylation pattern of CD19 species (p: precursor, m and m': two mature forms) differs because the glycosylation content of these species is different",
    "ncbi_link": "CD19: 930
CD81: 975"
  },
  {
    "caption": "E EC1 mutants of CD81 interfere with the accurate glycosylation of CD19. Chol: mutations at the cholesterol-binding site of CD81. CD81 constructs and CD19 (300 ng DNA) were co-transfected into the CD81-knockout 293T cells. Top, Anti-FLAG immunoblot was performed for CD19 with a C-FLAG tag. In presence of wildtype CD81 (wt), most CD19 is in the properly glycosylated mature form (m), and the overglycosylated m' form is not observed. With the EC1 mutants (A4 in particular), however, m' emerges and m shifts to high MW, indicating an alteration in the CD19 glycosylation. The level of intracellular p form is low with the wildtype CD81 or with the mutants. Bottom, Control experiment showing similar expression level of wild-type CD81 and CD81 mutants. Anti-V5 immunoblotting was conducted for the CD81 constructs with a C-V5 tag, and anti-actin immunoblotting was conducted on the same film.",
    "ncbi_link": "CD19: 930
CD81: 975"
  },
  {
    "caption": "A Migration of naïve Cd53-/- cultured primary pre-B cells to 100 ng/mL CXCL12 compared to WT littermate controls (n = 5 mice per group) over three independent experiments. Bars and error bars represent mean ± standard error of the mean. **p < 0.01 by two-way ANOVA.",
    "ncbi_link": "Cd53: 963"
  },
  {
    "caption": "B Migration of Cd53-/- pre-B cells transduced with empty, control, or mutant constructs in response to CXCL12 gradient, 3 days after transduction (n = 2-5 mice per group) over two independent experiments. Bars and error bars represent mean ± standard error of the mean. **p < 0.01 and ***p < 0.001 by two-way ANOVA.",
    "ncbi_link": "Cd53: 963"
  },
  {
    "caption": "A) Confocal microscopy time-series images of the increase in cytosolic Smac-GFP (magenta) in relation to the detection of RA-BAX/GB-DRP1 complexes (green) during apoptosis induction in MEF DRP1 KO cells. Scale bar 10 μm. Images are representative for n=3 independent experiments.",
    "ncbi_link": "DRP1: 74006"
  },
  {
    "caption": "B) Representative confocal microscopy images of U2OS BAX/BAK DKO cells of the interactions between RA-BAX variants and GB-DRP1, shown as green signal, 3 h after apoptosis induction. Mitochondria labeled with mito-BFP in magenta. Scale bar 10 μm.",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "C-E) Quantification of the interaction of DRP1 with variants of BAX based on the % cells with detectable RA-BAX/GB-DRP1 fluorescence signal (interacting cells) normalized to the number of mito-BFP positive cells. Box plots represent the interquartile (box), median (line) and SD (whiskers) of n=3 independent experiments (with n=100 cells each). Levels of significance were determined by paired two-tailed Student´s t-test (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001) compared to BAX wild type (WT).",
    "ncbi_link": "BAX: 581"
  },
  {
    "caption": "G) Representative confocal microscopy images of U2OS BAX/BAK DKO cells of the interactions between RA-BAX and GB-DRP1 variants, shown as green signal, 3 h after apoptosis induction. Mitochondria labeled with mito-BFP in magenta. Scale bar 10 μm.",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "H) Quantification of the interaction of DRP1 variants with BAX based on the % cells with detectable RA-BAX/GB-DRP1 fluorescence signal (interacting cells) normalized to the number of mito-BFP positive cells. Box plots represent the interquartile (box), median (line) and SD (whiskers) of n=3 independent experiments (with n=100 cells each). Significance was tested using paired two-tailed Student´s t-test (n.s. p > 0.05) compared to DRP1 WT.",
    "ncbi_link": "DRP1: 10059"
  },
  {
    "caption": "C) Forced dimerization of BAX and DRP1 in healthy cells induces their translocation to mitochondria and foci formation. Confocal microscopy images of U2OS BAX/BAK DKO cells transfected with FKBP-mCherry-DRP1 (red) and FRB-EGFP-BAX (green) and stained with MitoTracker Deep Red FM (cyan) were acquired before (0 min) and after induction of BAX/DRP1 dimerization (5-60 min). From top to down, the individual rows correspond to fluorescence signal of BAX and DRP1 and the merge of both together with the MitoTracker signal, respectively. Scale bar 20 µm.",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "E) Induced dimerization of BAX and DRP1 causes mitochondrial depolarization. U2OS BAX/BAK DKO cells were transfected as described in C) and stained with the mitochondrial membrane potential-sensitive dye MitoSpy NIR (cyan). Confocal microscopy images were acquired before (0 min) and after induced dimerization of BAX and DRP1 (10 min). Scale Bar 20 µm. F) Quantification of mitochondrial depolarization normalized to the number of transfected cells before (Ctrl) and after induced dimerization of BAX and DRP1 (Dim). Significance was tested using paired two-tailed Student´s t-test (* p < 0.05) compared to non-induced control. G",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "G-K) Induced dimerization of DRP1 with itself (G), BAX with itself (H), BAX with TOM20 (I) in U2OS BAX/BAK DKO cells, or BAX with DRP1 in HCT OctaKO cells (J,K), transected with FKBP- and FRB-mCherry DRP1 (G, red), FKBP- and FRB-EGFP-BAX (H, green), TOM20-mCherry-FKBP (red) and FRB-EGFP-BAX (green, I), respectively. Mitochondria were stained using MitoTracker Deep Red FM or MitoSpy NIR (cyan) as indicated. Scale bar 20 µm (G-I) and 10 µm (J,K ). All images are representative of n=3 independent experiments.",
    "ncbi_link": "BAK: 578
BAX: 581"
  },
  {
    "caption": "Effects of CRHR1 overexpression on the (C) neurosphere formation",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "Effects of CRHR1 overexpression on the (D) SOX2 expression (n = 3 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "E CRHR1 knockdown efficiency of shRNAs used in this study (n = 4 biological replicates).",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "Effects of CRHR1 knockdown on the (F) neurosphere formation,",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "Effects of CRHR1 knockdown on the (G) SOX2 expression n = 3 biological replicates for each experiment except for (G, n = 5 biological replicates).",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "Effects of CRHR1 knockdown on the (H) neurosphere morphology, n = 3 biological replicates for each experiment except for (G, n = 5 biological replicates).",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "Effects of CRHR1 knockdown on the (I) βIII-tubulin expression. n = 3 biological replicates for each experiment except for (G, n = 5 biological replicates).",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "J, K Immunostaining using anti-GFP (green) together with (J) anti-βIII-tubulin (clone TuJ1; red) (n = 5 biological replicates) or (K) anti-GFAP (red) antibodies (n = 3 biological replicates) after in vitro differentiation of E14.5 neural progenitor cells transduced with a lentiviral vector expressing shCRHR1.",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "A Embryonic brains that were intraventricularly electroporated CRHR1-expressing plasmids at E13.5 were harvested at E15.5 and immunostained using an anti-GFP (green) and SOX2 (red) antibodies. B Quantification of the cell fraction in each laminar layer in (A) (n = 3 biological replicates). C Percentage of SOX2+ cells among GFP+ cells in (A) (n = 4 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "D Embryonic brains were electroporated with shCRHR1 plasmids with or without shCRHR1-resistant CRHR1 expression vectors at E14.5, and samples were harvested at E17.5 for anti-GFP immunolabeling. GFP+ cell localization was quantified (bottom panel) (n = 5 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "E, F Brains electroporated with CRHR1 expression vectors at E13.5 were harvested at E15.5 and co-immunostained using anti-GFP (green) together with (E) anti-TBR2 (red) or (F) anti-CTIP2 (red) antibodies. n = 3 biological replicates.",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "G E14.5 Embryonic brains that were electroporated with CRHR1-expression vectors at E13.5 were pulse labeled with EdU and harvested at E15.5. Samples were then visualized for GFP (green), EdU (blue) and Ki67 (red) (n = 4 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "Analysis of the effects of CRHR1 knockdown on neural stemness- and cell-fate-regulating transcription factors in neural progenitor cells by (A) qPCR at 2 days post-transduction.",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "Analysis of the effects of CRHR1 knockdown on neural stemness- and cell-fate-regulating transcription factors in neural progenitor cells by (B) Western blotting (n = 3 biological replicates) at 2 days post-transduction.",
    "ncbi_link": "CRHR1: 12921"
  },
  {
    "caption": "The effects of CRHR1 overexpression on REST expression in neural progenitor cells analyzed by qPCR",
    "ncbi_link": "CRHR1: 1394
REST: 19712"
  },
  {
    "caption": "The effects of CRHR1 overexpression on REST expression in neural progenitor cells analyzed by (B) Western blotting (n = 6 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "E Double-immunolabeling of E15.5 brain sections electroporated in utero with CRHR1-expressing plasmid with or without shREST vectors at E13.5 using anti-GFP (green) and SOX2 (red) antibodies.",
    "ncbi_link": "CRHR1: 1394
REST: 5978"
  },
  {
    "caption": "H Embryonic brains were electroporated with shCRHR1 plasmids with or without REST expression vectors at E14.5, and brain samples were harvested at E17.5 for anti-GFP immunolabeling. I Quantification of GFP+ cell localization in (H)",
    "ncbi_link": "CRHR1: 1394
REST: 5978"
  },
  {
    "caption": "A, B Western blot analysis of E14.5 neural progenitor cells transduced with a lentiviral vector expressing (A) CRHR1 or (B) shCRHR1 using an anti-CREB and anti-phospho-CREB (pCREB) (S133) antibodies. n = 5 biological replicates.",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "C E14.5 neural progenitor cells were transduced with CRHR1-containing lentiviral vectors. At 2 days post-transduction, cells were treated with 10 µM H89 (PKA inhibitor) or 1 µM KN93 (CaM kinase inhibitor) for 8 h and harvested for Western blot analysis for CREB (top panel). Band intensities were quantified (bottom panel) (n = 3 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "D Double-immunolabeling of E15.5 brain sections electroporated in utero with CRHR1-expressing plasmid at E13.5 using anti-GFP (green) and pCREB (S133) (red) as primary antibodies. Immunostaining was quantified (right panel) (n = 5 biological replicates). White inset boxes were magnified and shown in the panels D' and D''.",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "E Double-immunolabeling of E15.5 brain sections electroporated in utero with CRHR1-expressing plasmid with or without a vector expressing CREB S133A, a dominant negative mutant form of CREB, at E13.5 using anti-GFP (green) and SOX2 (red) antibodies.",
    "ncbi_link": "CREB: 12912
CRHR1: 1394"
  },
  {
    "caption": "H Embryonic brains were electroporated with shCRHR1 plasmids with or without CREB expression vectors at E14.5, and then brain samples were harvested at E17.5 for anti-GFP immunolabeling. I Quantification of GFP+ cell localization in (L) (n ≥ 4 biological replicates).",
    "ncbi_link": "CREB: 12912
CRHR1: 1394"
  },
  {
    "caption": "(A) qPCR of E14.5 neural progenitor cells transduced with CREB-expressing lentiviral vectors, measuring REST mRNA",
    "ncbi_link": "CREB: 12912
REST: 19712"
  },
  {
    "caption": "(B) Western blot analyses (n = 3 biological replicates) of E14.5 neural progenitor cells transduced with CREB-expressing lentiviral vectors, measuring REST protein levels, respectively.",
    "ncbi_link": "CREB: 12912"
  },
  {
    "caption": "Dose-dependent inhibition of endogenous REST expression by a CREB inhibitor, 666-15. E14.5 neural progenitor cells were treated with the indicated concentrations of 666-15 for 48 h and subjected to (C) qPCR",
    "ncbi_link": "REST: 19712"
  },
  {
    "caption": "Inhibition of CRHR1-induced REST expression by 666-15. E14.5 neural progenitor cells transduced with a lentiviral vector expressing CRHR1 were treated with 20 nM of 666-15, and after 48 h, cells were lysed and subjected to (E) qPCR",
    "ncbi_link": "CRHR1: 1394
REST: 19712"
  },
  {
    "caption": "Inhibition of CRHR1-induced REST expression by 666-15. E14.5 neural progenitor cells transduced with a lentiviral vector expressing CRHR1 were treated with 20 nM of 666-15, and after 48 h, cells were lysed and subjected to (F) Western blot analyses (n = 4 biological replicates).",
    "ncbi_link": "CRHR1: 1394"
  },
  {
    "caption": "H Luciferase activity was measured using E14.5 neural progenitor cells transfected with CREB expression vectors and pGL3-Basic luciferase plasmids harboring the wild-type or mutated REST promoter at 2 days post-transfection (n = 3 biological replicates).",
    "ncbi_link": "luciferase: 
CREB: 12912
REST: 19712"
  },
  {
    "caption": "I A representative gel image of ChIP analysis showing association of CREB proteins with regions of the REST promoter by PCR amplification of putative CRE sequences in the REST promoter (n = 3 biological replicates).",
    "ncbi_link": "CRE: 2777477
REST: 19712"
  },
  {
    "caption": "J Immunolabeling of E15.5 brain sections electroporated in utero with CREB-expressing plasmids with or without shREST vectors at E13.5 using anti-GFP antibody. GFP+ cell localization was quantified (right panel) (n ≥ 5 biological replicates). The upper and lower dashed lines indicate the boundaries between the CP and IZ, and IZ and VZ/SVZ, respectively.",
    "ncbi_link": "CREB: 12912
REST: 5978"
  },
  {
    "caption": "A. Ncl and Pus7 mRNA levels (normalized to TBP) at different time points after LPS stimulation in c-mycwt/wt and c-myc∆/∆ cells. Data are presented as mean ± SD; n = 3.",
    "ncbi_link": "c-myc: 17869
Ncl: 17975
Pus7: 78697
TBP: 21374"
  },
  {
    "caption": "B. To quantify RNA synthesis, we exposed our cultures to a brief pulse of ethyl-uridine (EU) and measured its incorporation into RNA by light microscopy. The scatter plots show the nuclear Area as detected in the 2D plane (x axis, in pixels) versus the EU signal (y axis, as arbitrary units, AU) for each single cell identified by DAPI staining in c-mycwt/wt and c-myc∆/∆ populations at the indicated time points after LPS treatment. One representative experiment out of 5 is shown.",
    "ncbi_link": "c-myc: 17869"
  },
  {
    "caption": "C. Variation of each expressed mRNA at 4h of LPS treatment (log2FC, relative to time 0) for c-mycwt/wt (x-axis) and c-myc∆/∆ cells (y-axis), as measured by RNA-seq. Regulatory groups 1-6 and Grey Zone (GZ) are as defined in the text.",
    "ncbi_link": "c-myc: 17869"
  },
  {
    "caption": "E. Variations (log2FC) in mature and precursor RNAs (as measured by RNA-seq) and in the modeled rates (RNA synthesis, processing and degradation) for Myc dependent and independent genes. The grey scale represents the starting level for each parameter in unstimulated cells.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "B, C. Distribution of Myc at promoters (B) and distal sited (C) in LPS-treated B-cells (0, 2, 4 8h) and in B-cells in vivo, in either control c-mycwt/wt (C), pre-tumoral Eµ-myc mice (P) or tumors (T) 4[]. Each row represents a promoter-associated Myc peak within a 6 kb genomic interval (centered on the midpoint of the peak). The heatmap includes every annotated promoter in chromosome 1 (as representative of the whole genome) that was called as Myc-associated by ChIP-seq in at least one sample. For the same intervals, we also show the distribution of H3K4me1, H3K4me3, and H3K27ac in the in vivo control sample, and gene annotations (exons in red, introns in pink; + sense, - antisense strand).",
    "ncbi_link": "myc: 17869
c-myc: 17869"
  },
  {
    "caption": "B, C. Boxplots reporting LPS-induced changes (Log2FC) for each of the four RNAPII kinetic rates in c-mycwt/wt (wt) and c-myc∆/∆ cells for Myc-dependent (B) and Myc-independent (C) induced and repressed genes. p-values obtained with two-sample Wilcoxon tests for the comparison between c-mycwt/wt and c-myc∆/∆ cells are reported. The RNAPII ChIP-seq time-course was performed on two biological replicates (each on pools of cells from > 10 mice), and reads were merged after sequencing.",
    "ncbi_link": "c-myc: 17869"
  },
  {
    "caption": "F. Boxplots reporting LPS-induced changes (Log2FC) for each of the four RNAPII kinetic rates in c-mycwt/wt (wt) and c-myc∆/∆ cells for genes of clusters 1 and 9. p-values obtained with two-sample Wilcoxon tests for the comparison between c-mycwt/wt and c-myc∆/∆ cells are reported.",
    "ncbi_link": "c-myc: 17869"
  },
  {
    "caption": "G. Changes in Myc share in LPS treated versus untreated cells for the different clusters of panel d. p-values obtained with two-sample Wilcoxon tests for the comparison between c-mycwt/wt and c-myc∆/∆ cells are reported.",
    "ncbi_link": "c-myc: 17869"
  },
  {
    "caption": "G-K Co-immunostaining of NB-3 (green), PDGFR-β (red), and GFAP (blue) on serial sagittal sections from the same NB-3+/+spinal cord 14 days post-injury. (G1-K1) High-magnification images of boxed areas in (G-K), respectively.L Co-immunostaining of NB-3 (green), PDGFR-β (red), and GFAP (blue) on sagittal sections from the NB-3−/− spinal cord 14 days post-injury. (L1) High-magnification image of the boxed area in (L). The arrows indicate the lesion sites.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "M-Q Co-immunostaining of NB-3 (green), Fibronectin (red), and GFAP (blue) on serial sagittal sections from the same NB-3+/+spinal cord 14 days post-injury. (M1-Q1) High-magnification images of boxed areas in (M-Q), respectively.R Co-immunostaining of NB-3 (green), Fibronectin (red), and GFAP (blue) on sagittal sections from the NB-3−/− spinal cord 14 days post-injury. (R1) High-magnification image of the boxed area in (R). The arrows in (G-R) indicate the lesion sites.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "B-K Representative images of serial sagittal sections showing the main BDA-labeled corticospinal axons in NB-3+/+ (B-D) and NB-3−/− (E-G) mice 14 weeks after complete spinal transection. (H-J) High-magnification images of the areas in (E-G) (single asterisks), respectively. (K) High-magnification image of the area in (E) (double asterisk). The arrows indicate the lesion sites; the white dashed lines indicate the regenerative corticospinal axons extending into the distal spinal cord; the single asterisks in (E-G) indicate the lesion epicenters; the double asterisk in (E) indicates the axons extending from the caudal lesion border. Scale bars, 400 µm (B-G) and 100 µm (H-K).L Quantification of the intensity index of BDA-labeled axons at certain distances from the lesion border in (B-G). Data are represented as mean ± SEM. *p < 0.05, and **p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 25 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "A Time course of the change in BMS scores in NB-3+/+ and NB-3−/−mice as measured with the BMS rating scale after spinal cord complete transection. *p < 0.05; two-way ANOVA followed by Bonferroni's post-test. n= 25 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C Electrophysiology transmission across the spinal lesion site. In each group of NB-3+/+ and NB-3−/−mice, the electrophysiological responses in the caudal spinal cord were recorded in the condition of sham-operated or 12 weeks post-injury. The latencies and amplitudes of responses were analyzed and quantified in each group. n.s., not significant, *p < 0.05, and **p < 0.01; two-way ANOVA followed by Bonferroni's post-test. n= 10 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "E Representative images of coronal sections showing synapse formation between the glutamatergic corticospinal terminals and spinal neurons in NB-3+/+ and NB-3−/−mice. Corticospinal axons, neurons, and glutamatergic terminals of corticospinal axons were labeled with BDA (red), Tuj1 (blue) and vGlut1/2 (green), respectively. Each group showed the data from the rostral and caudal spinal cord in the condition of sham-operated or 12 weeks post-injury. Scale bar, 20 μm.F Quantification of the number of glutamatergic corticospinal synapses per neuron in each group. n.s., not significant, **p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 15 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "A, B Western blot analysis (A) and quantification (B) of NB-3 expression in cultured pyramidal neurons infected with lentivirus encoding negative control (LV-nc-GFP) and that encoding NB-3 shRNA (LV-NB-3 shRNA-GFP). NB-3 expression levels were normalized by b-tubulin. ***p < 0.001; one sample t-test. Data were analyzed from 5 independent experiments.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C-E Sagittal sections showing the BDA-labeled corticospinal axons in injured spinal cords following cortical injection of LV-nc-GFP (C) and LV-NB-3 shRNA-GFP (D). High-magnification image (E) of the area in (D) (asterisk).F, J Quantification of the intensity index of BDA-labeled axons at certain distances from the lesion border in (C, D, G, and H). *p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 19 mice per group in (F), and n= 17 mice per group in (J).",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "G-I Sagittal sections showing the corticospinal axons in injured spinal cords following injection of LV-nc-GFP (G) and LV-NB-3 shRNA-GFP (H) into the lesion sites. High-magnification image (I) of the area in (H) (asterisk). The arrows in (C-E and G-H) indicate the lesion sites; the asterisks in (D and H) indicate the lesion epicenters; the white dashed lines in (D and H) indicate the regenerative corticospinal axons extending into the distal spinal cord.F, J Quantification of the intensity index of BDA-labeled axons at certain distances from the lesion border in (C, D, G, and H). *p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 19 mice per group in (F), and n= 17 mice per group in (J).",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C Co-immunoprecipitation of NB-3-Myc with NB-3-HA from co-transfected COS1 cells.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "L-Q NB-3+/+ (L and M) and NB-3−/− (O and P) pyramidal neurons were co-cultured with astrocytes that did not (L and O) or did (M and P) express NB-3, and immunostained for Tuj1, NB-3, and GFAP (L, M, O and P). NB-3+/+ pyramidal neurons (N) and NB-3−/−pyramidal neurons that overexpressed NB-3ΔECD-Myc (Q) were co-cultured with astrocytes that overexpressed NB-3ΔECD-Myc, and immunostained for Tuj1, Myc, and GFAP (N and Q).R The length of neurites on astrocytes relative to total neurite length. n.s., not significant, and *p < 0.05; one-way ANOVA followed by Bonferroni post-test. The neurite lengths of more than 150 pyramidal neurons from 4 independent experiments in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "A Layer V cortex explants from E18.5 NB-3+/+ and NB-3−/−mice were cultured in medium supplemented with either Fc or NB-3-Fc (50 μg/ml).B Quantification of neurite outgrowth in (A). n.s., not significant, **p < 0.01; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from more than 50 layer V cortical explants from 5 independent experiments in each group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C Pyramidal neurons of NB-3+/+ and NB-3−/− mice were cultured in medium supplemented with either Fc or NB-3-Fc (50 μg/ml). The neurons were co-stained for Ctip2, NB-3, and Rhodamine phalloidin. (C1-C4) High-magnification images of the growth cones (white arrowheads) of the neurons in (C), respectively.D Quantification of neurite length in (C), and the percentage of collapsed growth cones in (C). n.s., not significant, *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from more than 300 corticospinal neurons from 6 independent experiments in each group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "A Images of coronal sections of layer Vsensorimotor cortex from NB-3+/+ and NB-3−/−mice after SCI. Corticospinal neurons were retrogradely labeled with Fluorogold (FG), and coronal sections were co-stained with p-mTOR (A) (arrowheads).B Quantification of fluorescence intensity of p-mTOR in FG-labeled corticospinal neurons in (A). *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. The intensities of more than 300 corticospinal neurons from 3 mice in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C Images of coronal sections of layer Vsensorimotor cortex from NB-3+/+ and NB-3−/−mice after SCI. Corticospinal neurons were retrogradely labeled with Fluorogold (FG), and coronal sections were co-stained with p-S6 (S240/244) (C) (arrowheads).D Quantification of fluorescence intensity of p-S6 (S240/244) in FG-labeled corticospinal neurons in (C). *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. The intensities of more than 300 corticospinal neurons from 3 mice in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "E-H Western blot analysis and quantification of the expression of p-Akt/Akt (E and F) and p-S6 (S240/244) (G and H) in sensorimotor cortex from NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from 3 independent experiments each including 3 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "I, K, M, O Expression of Akt (I), p-Akt (K), p-mTOR (M), and p-S6 (S240/244) (O) in NB-3+/+ pyramidal neuron-astrocyte co-cultures. The astrocytes were transfected either with NB-3-Myc or a control vector. The dashed lines outline the astrocytes. The asterisks indicate the NB-3-expressing astrocytes.J, L, N, P Quantification of fluorescence intensity of Akt (J), p-Akt (L), p-mTOR (N), and p-S6 (S240/244) (P), respectively, in pyramidal neurons of the co-cultures in (I, K, M, and O). n.s., not significant, and *p < 0.05; one sample t-test. The intensities of more than 300 pyramidal neurons from 6 independent experiments in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "A Co-immunostaining of CHL1 (blue), NB-3 (green), and BDA (red) in injured spinal cords of NB-3+/+ (A1) and NB-3−/− (A5) mice. (A2-A4 and A6-A8) High-magnification images of boxed areas in (A1 and A5), respectively. Images in (A2 and A6) are presented as single-channel fluorescence images in (A3-A4 and A7-A8), respectively.B Quantification of fluorescence intensity of CHL1 at the spinal lesion sites of NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. n = 11 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C, D Western blot analysis (C) and quantification (D) of CHL1 expression in spinal lesion areas of NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05, **p < 0.01, and ***p < 0.001; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from 3 independent experiments each including 2 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "E Co-immunoprecipitation of NB-3 and CHL1 from spinal cord lesion areas of NB-3+/+ and NB-3−/−mice.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "F Co-immunostaining of CHL1 and NB-3 in FG-labeled corticospinal neurons (arrowheads) of NB-3+/+ and NB-3−/− mice 14 days post-injury (dpi).G Quantification of the fluorescence intensity of CHL1 in (F). *p < 0.05, and **p < 0.01; one-way ANOVA followed by Bonferroni post-test. The intensities of more than 300 corticospinal neurons from 3 mice in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "H, I Western blot analysis (H) and quantification (I) of CHL1 expression in sensorimotor cortices of NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05; one-way ANOVA followed by Bonferroni post-test. Data were analyzed from 3 independent experiments each including 3 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "J CHL1 expression in the somas and axons of NB-3+/+ and NB-3−/− pyramidal neurons when co-culturing with NB-3-expressing astrocytes (dashed lines and asterisks) or astrocytes that didn't express NB-3 (dashed lines). Co-localization of CHL1 and NB-3 in astrocytes overexpressed NB-3 (asterisks). Co-localization of CHL1 and NB-3 in the somas and axons of co-cultured NB-3+/+ pyramidal neurons (arrowheads). Left inset, high-magnification view of the soma (white arrowhead). Right inset, high-magnification view of the axon tip (green arrowhead).K Quantification of fluorescence intensity of CHL1 in (J). *p < 0.05, **p < 0.01, and ***p < 0.001; one-way ANOVA followed by Bonferroni post-test. The intensities of more than 300 astrocytes or pyramidal neurons from 3 independent experiments in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "L-N Sagittal sections showing the corticospinal axons in injured spinal cords following injection of LV-nc-GFP (L) and LV-CHL1 shRNA-GFP (M) into both the sensorimotor cortex and lesion sites. High-magnification image (N) of the area in (M) (asterisk). The arrows indicate the lesion sites; the asterisk indicates the lesion epicenter.O Quantification of intensity index of BDA-labeled axons at certain distances from the lesion border in (L and M). *p < 0.05 and **p < 0.01; two-way ANOVA followed by Fisher's LSD. n= 9 mice in (L), and n= 10 mice in (M).",
    "ncbi_link": "CHL1: 12661"
  },
  {
    "caption": "A Co-immunostaining of PTPσ (blue), NB-3 (green), and BDA (red) at spinal lesion sites of NB-3+/+ (A1) and NB-3−/− (A6) mice. (A2-A5 and A7-A10) High-magnification images of boxed areas in (A1 and A6) showing PTPσ expression at the terminations of BDA-labeled corticospinal axons, respectively. Images in (A2 and A7) are presented as single-channel fluorescence images in (A3-A5 and A8-A10), respectively.B Quantification of fluorescence intensity of PTPσ at BDA-labeled axonal terminations of NB-3+/+ and NB-3−/− mice after SCI. *p < 0.05; one-way ANOVA followed by Bonferroni post-test. n = 12 mice per group.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "C Co-immunostaining of PTPσ and NB-3 in the FG-labeled corticospinal neurons (arrowheads) of NB-3+/+ and NB-3−/− mice 14 days post-injury (dpi). Insets, only the signals from PTPσ and FG in NB-3+/+ corticospinal neurons (red arrowheads) were visualized.D Quantification of fluorescence intensity of PTPσ in (C). *p < 0.05; one-way ANOVA followed by Bonferroni post-test. The intensities of more than 300 corticospinal neurons from 3 mice in each group were quantified.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "G PTPσ expression in NB-3+/+ and NB-3−/− pyramidal neurons when co-culturing with NB-3-expressing astrocytes (dashed lines and asterisks) or astrocytes that didn't express NB-3 (dashed lines). Upper inset, high-magnification view of the soma (white arrowhead). Lower inset, high-magnification view of the axon tip (green arrowhead).H Quantification of fluorescence intensity of PTPσ in (G). n.s., not significant, and *p < 0.05; one-way ANOVA followed by Bonferroni post-test.",
    "ncbi_link": "NB-3: 53870"
  },
  {
    "caption": "I Expression of PTPσ, p-Akt, p-mTOR, and p-S6 (S240/244) in pyramidal neurons that expressed PTPσ shRNA-GFP. A control plasmid expressing GFP was transfected as the negative control (nc).J Quantification of fluorescence intensity of PTPσ, p-Akt, p-mTOR, and p-S6 (S240/244) in (I). *p < 0.05; one sample t-test. The intensities of more than 300 pyramidal neurons from 4 independent experiments in each group in (H) and (J) were quantified, respectively.",
    "ncbi_link": "PTPσ: 19280"
  },
  {
    "caption": "K-M Sagittal sections showing the corticospinal axons in injured spinal cords following injection of LV-nc-GFP (K) and LV-PTPσ shRNA-GFP (L) into the sensorimotor cortex. High-magnification image (M) of the area in (L) (asterisk). The arrows indicate the lesion sites; the asterisk indicates the lesion epicenter.N Quantification of the intensity index of BDA-labeled axons at certain distances from the lesion border in (K and L). *p < 0.01; two-way ANOVA followed by Fisher's LSD. n = 8 mice in (K), and n = 10 mice in (L).",
    "ncbi_link": "PTPσ: 19280"
  },
  {
    "caption": "A-D The morphology of uninjected, FLT3/WT mRNA and FLT3/ITD mRNA injected (150 ng per embryo) embryos on day 2 post fertilization (dpf). Data information: ov: otic vesicles Scale bar = 500 μm.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "E-H Whole mount in situ hybridization (WISH) of notochord-specific marker col9a2 in uninjected, FLT3/WT mRNA and FLT3/ITD mRNA injected embryos on 2 dpf. Data information: ov: otic vesicles; cm: cephalic mesoderm; nc: notochord. Scale bar = 500 μm.",
    "ncbi_link": "col9a2: 321212
FLT3: 2322"
  },
  {
    "caption": "FLT3 signaling was detected by Western blotting in 293FT cells-transfected with FLT3/ITD mRNA (I)",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "FLT3 signaling was detected by Western blotting in zebrafish embryos-injected with FLT3/ITD mRNA (J).",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "K The effect of FLT3 inhibitor quizartinib (Qui) on the dorsalization and axis-duplication phenotype-induced by FLT3/ITD mRNA injection in zebrafish. Data information: the experiments were performed in triplicates and the data are presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test). NS, not significant.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "Quantification of fst expression by RT-qPCR (L) after FLT3/ITD overexpression in zebrafish embryos at 6 hpf. Data information: the experiments were performed in triplicates and the data are presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test). NS, not significant.",
    "ncbi_link": "FLT3: 2322
fst: 100004116"
  },
  {
    "caption": "Quantification of fst expression by Western Blotting (M), after FLT3/ITD overexpression in zebrafish embryos at 6 hpf.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "Quantification of fst expression by WISH (N) after FLT3/ITD overexpression in zebrafish embryos at 6 hpf.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "A-C WISH of fst in FLT3/WT- (A), FLT3/ITD- plasmid DNA injected zebrafish embryos without (B) or with (C) quizartinib treatment (2.5 μM) from 6 to 36 hpf. fst expression was expanded by FLT3/ITD DNA in 86% of embryos (B, arrow, 32/37) which could be effectively blocked by treating with FLT3 inhibitor quizartinib in 83% of embryos (C, 29/35). Data information: Scale bar = 500 μm.",
    "ncbi_link": "FLT3: 2322
fst: 100004116"
  },
  {
    "caption": "Generation and characterization of FLT3/ITD-transgenic zebrafish. GFP expression was detected by florescent microscopy (F-H) and in blood circulation and thymus by WISH (I and J, blue arrow) in WT sibling and Runx1-FLT3/ITD transgenic zebrafish (F1) embryos at 4 dpf. FLT3/ITD-positive zebrafish (F1) were confirmed by PCR genotyping of GFP and FLT3/ITD using genomic DNA from fin clip of WT siblings and Runx1-FLT3/ITD transgenic zebrafish (F1) at two months old. Fish 4, 5 and 6 showed germline transmission of FLT3/ITD transgene (K). Data information: Scale bar = 500 μm.",
    "ncbi_link": "GFP: 
FLT3: 2322
Runx1: 12394"
  },
  {
    "caption": "Kidney marrow (KM) was collected from Runx1-FLT3/ITD transgenic zebrafish (F1) at 18 months old. The morphology and hematopoietic composition of KM from WT siblings (n = 6) and Runx1-FLT3/ITD transgenic (n = 6) zebrafish were examined by Giemsa staining (L) and flow cytometry (abbreviation for panel M: M, Myeloid cells; P, Progenitor cells; L, Lymphoid cells; E, Erythroid cells). Data are presented in box plot. **P<0.01 (Student's t-test).",
    "ncbi_link": "FLT3: 2322
Runx1: 12394"
  },
  {
    "caption": "Kidney marrow (KM) was collected from Runx1-FLT3/ITD transgenic zebrafish (F1) at 18 months old. The morphology and hematopoietic composition of KM from WT siblings (n = 6) and Runx1-FLT3/ITD transgenic (n = 6) zebrafish were examined by flow cytometry Data are presented in box plot. The whiskers, boxes, and central lines in panel N represented the minimum-to-maximum values, 25th-to-75th percentile, and the 50th percentile (median), respectively. **P<0.01 (Student's t-test).",
    "ncbi_link": "FLT3: 2322
Runx1: 12394"
  },
  {
    "caption": "O Expression of fst was detected by RT-qPCR in KM from WT sibling and Runx1-FLT3/ITD transgenic zebrafish at 18 months old. The RT-qPCR experiments were performed in triplicates and data were presented as mean ± SEM. **P<0.01.",
    "ncbi_link": "FLT3: 2322
fst: 100004116
Runx1: 12394"
  },
  {
    "caption": "P Detection of FST expression, p-ERK1/2, and p-CREB in mononuclear cells from normal peripheral blood stem cell (PBSC) and FLT3/ITD AML patients (diagnostic samples with leukemia blasts > 80%) by Western blotting. ^: non-specific staining of p-ATF1 protein due to the conserved motif.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "B-C The direct binding of p-CREB to human FST promoter was detected by ChIP-PCR (B) and ChIP-qPCR (C). c-Fos was used as positive control of p-CREB target gene. Normal IgG was used as negative control of ChIP. Data information the experiments were performed in triplicates, and the data were presented as mean ± SEM. **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "CREB: 1385
c-Fos: 2353
FST: 10468"
  },
  {
    "caption": "D Dual luciferase assay demonstrating the direct binding of pCREB on human FST promoter. pRL-CMV, Renilla luciferase vector; pGL-CRE- and pGL-CRE+, firefly luciferase expression driven by human FST promoter with deleted CRE site (CRE-) or wildtype (CRE+); p-GFPSpark, GFP expressing vector; p-CREBY134F, CREBY134F-GFP expressing vector. Data information: the experiments were performed in triplicates, and the data were presented as mean ± SEM. **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "GFP: 
GFPSpark: 
luciferase: 
CRE: 2777477
CREB: 1385
FST: 10468
FST: 100004116"
  },
  {
    "caption": "E FST expression and FLT3/ITD signaling were detected by Western blotting in Ba/F3-parental (P in short) and Ba/F3-FLT3/ITD (ITD in short) cells.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "F-H Phosphor-flow analysis of p-CREB in Ba/F3-parental, Ba/F3-FLT3/ITD, and Ba/F3-FLT3/ITD cells-treated with FLT3 inhibitor Quizartinib (Qui in short). Isotype antibody were used as control to calculate the mean fluorescence intensity (MFI) ratio (F-G). The transcription and expression of Fst was detected by RT-qPCR after Quizartinib treatment (10 nM) in Ba/F3-FLT3/ITD cells for one day (H). Data information: the experiments were performed in triplicates, and the data were presented as mean ± SEM. **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "FLT3: 2322
Fst: 14313"
  },
  {
    "caption": "I-K The expression of FST and phosphorylation of CREB were detected by Western Blotting (I and K) and phospho-flow analysis (J) in MOLM-13 (I) and Ba/F3-FLT3/ITD (K) cells treated with Quizartinib and BRD7389 for one day, respectively. Data information: the experiments were performed in triplicates, and the data were presented as mean ± SEM. **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "L RSK and FST expression were detected by Western Blotting after p90RSK knockout by CRISPR/Cas9 in MOLM-13 cells.",
    "ncbi_link": "CRISPR: 
p90RSK: 6195
Cas9: 901176"
  },
  {
    "caption": "M The phosphorylation of CREB and FST expression were detected by Western Blotting in Ba/F3-FLT3/ITD cells treated with CREB inhibitor 666-15 for one day. ^: non-specific staining of p-ATF1 protein due to the conserved motif.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "N CREB and FST expression were detected by Western Blotting after CREB knockout by CRISPR/Cas9 in MOLM-13 cells.",
    "ncbi_link": "CRISPR: 
CREB: 1385
Cas9: 901176"
  },
  {
    "caption": "O The growth of Ba/F3-parental (with IL-3), Ba/F3-FLT3/ITD (without IL-3) and Ba/F3-FLT3/ITD (with IL-3) cells was measured after three days treatment of CREB inhibitor 666-15 in vitro. Data information: the experiments were performed in triplicates, and the data were presented as mean ± SEM. **P<0.01, ***P<0.001 (Student's t-test).",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "P The rescue effect of CREB inhibitor 666-15 on FLT3/ITD-induced dorsalization and axis duplication in zebrafish embryos at 1 dpf.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "FST317 and FST344 overexpression resulted in significant increases of FST transcription by RT-qPCR and protein by Western Blot (B) Green, ML-2-GFP; Blue, ML-2-FST317; Red, ML-2-FST344. The RT-qPCR experiments were performed in triplicates (B). Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test). ns: Not significant.",
    "ncbi_link": "GFP: 
FST: 10468"
  },
  {
    "caption": "FST317 and FST344 overexpression promoted ML-2 cell growth in vitro (C). Green, ML-2-GFP; Blue, ML-2-FST317; Red, ML-2-FST344. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test). ns: Not significant.",
    "ncbi_link": "GFP: 
FST: 10468"
  },
  {
    "caption": "D-E The clonogenicity of ML-2 overexpressing GFP, FST317, and FST344 in vitro for 14 days. The CFU experiments were performed in triplicates (E). Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test). ns: Not significant.",
    "ncbi_link": "GFP: 
FST: 10468"
  },
  {
    "caption": "The engraftment of ML-2 (with luciferase gene) overexpressing GFP, FST317, and FST344 was quantified by bioluminescence imaging (F and G) Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test). ns: Not significant.",
    "ncbi_link": "GFP: 
luciferase: 
FST: 10468"
  },
  {
    "caption": "The engraftment of ML-2 (with luciferase gene) overexpressing GFP, FST317, and FST344 and the survival of ML-2-engrafted NSG mice in vivo was recorded (H). Survival curve in panel H was analyzed by Log-rank test. *P<0.05, **P<0.01.",
    "ncbi_link": "GFP: 
luciferase: 
FST: 10468"
  },
  {
    "caption": "RNA-seq of upregulation of RET, IL2RA and CCL5 after FST344 overexpression in ML-2 cells.",
    "ncbi_link": "CCL5: 6352
FST: 10468
IL2RA: 3559
RET: 5979"
  },
  {
    "caption": "RT-qPCR validation of upregulation of RET, IL2RA and CCL5 after FST344 overexpression in ML-2 cells. RT-qPCR experiments were performed in triplicates (J). Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01, ***P<0.001 (Student's t-test). ns: Not significant.",
    "ncbi_link": "CCL5: 6352
FST: 10468
IL2RA: 3559
RET: 5979"
  },
  {
    "caption": "Overall survival analysis of patients from TCGA-AML based on the differential expression of IL2RA",
    "ncbi_link": "IL2RA: 3559"
  },
  {
    "caption": "Overall survival analysis of patients from TCGA-AML based on the differential expression of CCL5.",
    "ncbi_link": "CCL5: 6352"
  },
  {
    "caption": "M Activation of MAPK/ERK pathway in ML-2 by FST344 overexpression were validated by Western Blotting. Scale bar = 1 mm.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "A FST knockdown in MOLM-13 by shRNA effectively reduced FST expression.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The morphology were measured after FST knockdown in vitro. Scale bar = 10 μm.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The apoptosis (C) measured after FST knockdown in vitro. Scale bar = 10 μm. The apoptosis assays (C) were performed in triplicates. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The clonogenicity of MOLM-13 (D and E) were measured after FST knockdown in vitro. Scale bar = 10 μm. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The engraftment of MOLM-13 after FST knockdown was detected by flow cytometry of human CD45 and mouse CD45.1 positive cells in recipient mouse BM aspiration at week 2 post transplantation.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The engraftment of MOLM-13 after FST knockdown was detected by flow cytometry of human CD45 and mouse CD45.1 positive cells in recipient mouse BM aspiration at week 2 post transplantation. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 100004116"
  },
  {
    "caption": "The effect of FST knockdown on the survival of NSG mice-engrafted with MOLM-13. scr: scrambled sequence control (7 mice); sh: short hairpin RNA (8 mice for sh1 and sh2 respectively). The survival curve was analyzed by Log-rank test. **P<0.01.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The morphology of MOLM-13 after FST knockout by CRISPR/Cas9 in vitro. Scale bar = 10 μm.",
    "ncbi_link": "CRISPR: 
FST: 10468
Cas9: 901176"
  },
  {
    "caption": "The clonogenicity of MOLM-13 after FST knockout by CRISPR/Cas9 in vitro. Scale bar = 10 μm. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "CRISPR: 
FST: 10468
Cas9: 901176"
  },
  {
    "caption": "The engraftment of MOLM-13 after FST knockout was detected by flow cytometry of human CD45 and mouse CD45.1 positive cells in recipient mouse BM aspiration at week 2 post transplantation.",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "The engraftment of MOLM-13 after FST knockout was detected by flow cytometry of human CD45 and mouse CD45.1 positive cells in recipient mouse BM aspiration at week 2 post transplantation. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "E The effect of FST knockout on the survival of NSG mice-engrafted with MOLM-13 cells. Cas 9: Cas 9 only (10 mice); sgRNA#3: Cas 9 + sgRNA#3 (10 mice); sgRNA#4: Cas 9 + sgRNA#4 (8 mice). Data information: survival curves were analyzed by Log-rank test. *P<0.05.",
    "ncbi_link": "FST: 10468
Cas 9: 901176"
  },
  {
    "caption": "F The knockdown efficiency of different FST-specific antisense oligoes (ASOs) in MOLM-13 cells was detected by RT-qPCR after three days treatment in vitro. The knockdown and RT-qPCR experiments were performed in triplicates. Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 10468"
  },
  {
    "caption": "Flt3/ITD knock-in mouse were genotyped (A).",
    "ncbi_link": "Flt3: 2322"
  },
  {
    "caption": "The spleen weight (B and C, 4 mice each) were measured in WT siblings and Flt3/ITD-knock-in mice (8 mice each). data were presented in box plot. The whiskers, boxes, and central lines represented the minimum-to-maximum values, 25th-to-75th percentile, and the 50th percentile (median), respectively. **P<0.01 (Student's t-test).",
    "ncbi_link": "Flt3: 2322"
  },
  {
    "caption": "The serum Fst level (D) were measured in WT siblings and Flt3/ITD-knock-in mice (8 mice each). data were presented in box plot. The whiskers, boxes, and central lines represented the minimum-to-maximum values, 25th-to-75th percentile, and the 50th percentile (median), respectively. **P<0.01 (Student's t-test).",
    "ncbi_link": "Flt3: 2322"
  },
  {
    "caption": "After FST knockdown, serum FST level was also measured in MOLM-13-engrafted NSG mice at week 2 post injection (H, 3 mice for each group). Data information: data were presented as mean ± SEM. *P<0.05, **P<0.01 (Student's t-test).",
    "ncbi_link": "FST: 14313"
  },
  {
    "caption": "L Correlation between serum FST levels and leukemia blast percentage from FLT3/ITD-mutated AML at diagnosis. Correlation analysis (Pearson correlation coefficient) was performed by Graphpad Prism 6.",
    "ncbi_link": "FLT3: 2322"
  },
  {
    "caption": "(a) Atg7+/− mice were generated as described in the Methods. PCR was done employing genomic DNA and primers flanking the floxed Atg7 regions. Arrows indicate wild-type Atg7 band in Atg7+/+ mice, increased size of PCR band due to inserted flox sequence in Atg7F/+ mice and decreased size of PCR band due to Cre-mediated deletion in Atg7+/− mice, respectively.",
    "ncbi_link": "Cre: 
Atg7: 74244"
  },
  {
    "caption": "(b) RT-PCR (left) and real-time RT-PCR (right) were performed using total RNA prepared from tissues of Atg7+/− or control Atg7+/+mice, and primers specific for Atg7 or β-actin sequence. Fold changes of the RT-PCR band intensities are shown (left). *P0.05, **P0.01, ***P0.001; Student's t-test, n=3.",
    "ncbi_link": "β-actin: 
Atg7: 74244"
  },
  {
    "caption": "(c) Tissue lysate from fasted 12-week-old Atg7+/− and control Atg7+/+mice was subjected to immunoblot analysis using anti-LC3 or -p62 antibody. Fold changes of the immunoblot band intensities are shown (middle and right). **P0.01, ***P0.001; Student's t-test, n=3.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(d) Cell lysate of Atg7+/+, Atg7+/− and Atg7−/− MEFs was subjected to immunoblot analysis using antibodies specific for LC3 and p62 after rapamycin (Rap) or control solvent (dimethyl sulfoxide, DMSO) treatment for 3 h. Fold changes of the immunoblot band intensities are shown (middle and right). *P0.05, **P0.01, ***P0.001; Student's t-test, n=3.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(e) Sections of the liver and muscle tissues from fasted 12-week-old GFP-LC3+-Atg7+/+ and GFP-LC3+-Atg7+/− mice were subjected to fluorescent microscopy to examine GFP-LC3 puncta (left). The number of GFP-LC3 puncta was counted (right). Scale bars, 10 μm. *P0.05; Student's t-test, n=5.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(f) Tissue lysates were prepared from the liver of fasted Atg7+/+ and Atg7+/− mice 4 h after leupeptin administration, and immunoblotting was done. Fold changes of the immunoblot band intensities are shown (right). *P0.05; Student's t-test, n=3.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(a) Non-fasting blood glucose level was monitored weekly in Atg7+/+, Atg7+/−, Atg7+/+-ob/ob and Atg7+/−-ob/ob mice. ***P0.001; two-way ANOVA.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "(e) Tissue lysates from Atg7+/+-ob/w, Atg7+/−-ob/w, Atg7+/+-ob/ob and Atg7+/−-ob/ob mice were prepared before and 7 min after injection of 5 U kg−1 regular insulin (Ins) into the tail vein, and subjected to immunoblot analysis using antibodies specific for phospho-Akt S473 and total Akt. Numbers below immunoblot bands indicate the fold changes normalized to control bands.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "(d) Immunoblot analysis was performed using anti-phospho-p53 and -p53 antibodies. p21 and β-actin mRNA expression was evaluated by RT-PCR. Numbers below immunoblot bands indicate the fold changes normalized to control bands.",
    "ncbi_link": "β-actin: 
p21: 12575"
  },
  {
    "caption": "(b) Tissues of ob/w and ob/ob mice were subjected to EM, and the number of autophagosomes was counted. ***P0.001; Student's t-test.",
    "ncbi_link": "ob: 16846"
  },
  {
    "caption": "(d) Tissue lysates were prepared from the liver of fed ob/w or ob/ob mice 4 h after leupeptin administration, and immunoblotting was performed. Numbers below immunoblot bands indicate the fold changes normalized to control bands.",
    "ncbi_link": "ob: 16846"
  },
  {
    "caption": "(f) Atg7+/+ and Atg7+/− primary MEFs were loaded with a mixture of the indicated concentrations of PA and OA for 48 h, and TG content was estimated by ORO staining. **P0.01, ***P0.001; two-way ANOVA, n=4.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(b) Total mRNA was extracted from each tissue, and RT-PCR was done using primers specific for Tnfa, Il6, F4/80 or pro-Il1b. The expression of pro-Il1b was determined using SVF fraction of WAT tissue.",
    "ncbi_link": "F4/80: 13733
Il1b: 16176
Il6: 16193
Tnfa: 21926"
  },
  {
    "caption": "(a) Atg7+/− and control Atg7+/+ mice were fed HFD or normal chow diet (NCD), and non-fasting blood glucose levels were monitored. *P0.05, **P0.01; Student's t-test.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(b) Imatinib (25 mg kg−1), trehalose (2 g kg−1) or PBS was injected intraperitoneally into 12-week-old diabetic Atg7+/−-ob/ob mice 3 times a week, and the blood glucose level was monitored. ***P0.001, ###P0.001; two-way ANOVA.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "(c) IPGTT were performed after treatment of Atg7+/−-ob/ob mice with imatinib or trehalose for 8 weeks. #P0.05; ##P or **P0.01; ###P or ***P0.001; Student's t-test.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "(d) ITT were performed after treatment of Atg7+/−-ob/ob mice with imatinib or trehalose for 8 weeks. #P0.05; ##P or **P0.01; ###P or ***P0.001; Student's t-test.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "(e) Regular insulin (Ins) was injected into the tail vein of Atg7+/−-ob/ob mice that were treated with imatinib or PBS for 8 weeks. Seven minutes later, tissue lysates were prepared and subjected to immunoblotting.",
    "ncbi_link": "Atg7: 74244
ob: 16846"
  },
  {
    "caption": "A. Confocal images of mitochondrial morphology in wild-type (WT) and Drp1-/- 293T cells transfected with empty vector (left panel) and Myc-hFis1 (right panel), stained with MitoTracker (red) followed by immunostaining with anti-Myc antibody (green).",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "B. Quantitative analyses of fragmented mitochondria size (mean area (μm2) per mitochondrion) after Myc-hFis1 overexpression in WT and Drp1-/- 293T cells using Image J software (Particle analysis) in three independent experiments. In each cell, only dispersed individual mitochondria were analyzed. The total number of mitochondria (mito) analyzed is indicated for each condition.",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "C. Quantitative analysis of mean mitochondria number per cell in WT and Drp1-/- 293T cells overexpressing Myc-hFis1 using Image J software (Particle analysis) in three independent experiments.",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "E. Percentages of cells with indicated mitochondrial morphologies in WT and Drp1-/- 293T cells transfected with empty vector (control), Myc-hFis1 and either Myc- or GFP-tagged mutants as indicated in three independent experiments.",
    "ncbi_link": "GFP: 
Myc: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "A. Confocal images of mitochondrial morphology in WT 293T cells treated with scrambled siRNA (control) and Dyn2 siRNA as indicated, followed by transfection with empty vector (left panel) and Myc-hFis1 (right three panels) as indicated. Cells were stained with MitoTracker (red) followed by immunostaining with anti-Myc antibody (green).",
    "ncbi_link": "Myc: 
Dyn2: 1785
hFis1: 51024"
  },
  {
    "caption": "C. Percentages of cells with indicated mitochondrial morphologies in WT 293T cells treated with scrambled siRNA and Dyn2 siRNA as indicated, followed by transfection with empty vector or Myc-hFis1 in three independent experiments.",
    "ncbi_link": "Myc: 
Dyn2: 1785
hFis1: 51024"
  },
  {
    "caption": "D. Confocal images of mitochondrial morphology in Drp1-/- 293T cells treated with scrambled siRNA and Dyn2 siRNA as indicated, followed by transfection with empty vector (left panel) and Myc-hFis1 (right three panels). Cells were stained with MitoTracker (red) followed by immunostaining with anti-Myc antibody (green). Representative examples of tubular, fragmented and tubular cluster phenotypes are indicated.",
    "ncbi_link": "Myc: 
Drp1: 10059
Dyn2: 1785
hFis1: 51024"
  },
  {
    "caption": "E. Western blot of Dyn2, Myc-hFis1 and GAPDH in Drp1-/- 293T cells collected from the experiments in (D).",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "F. Percentages of cells with indicated mitochondrial morphologies in Drp1-/- 293T cells treated with scrambled siRNA or Dyn2 siRNA, followed by transfection with empty vector or Myc-hFis1 as indicated in three independent experiments.",
    "ncbi_link": "Myc: 
Drp1: 10059
Dyn2: 1785
hFis1: 51024"
  },
  {
    "caption": "A. Confocal images of mitochondrial morphology in Drp1-/- 293T cells transfected with scrambled siRNA (control) or with hFis1-siRNA and then stained with MitoTracker (red).",
    "ncbi_link": "Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "B. Confocal images of mitochondrial morphology in Drp1-/- 293T cells transfected with either Mfn1-Myc, Mfn2-Myc or OPA1-Myc, stained with MitoTracker (red) followed by immunostaining with anti-Myc antibody (green).",
    "ncbi_link": "Myc: 
Drp1: 10059
Mfn1: 55669
Mfn2: 9927
OPA1: 4976"
  },
  {
    "caption": "C. Percentages (mean ± s.e.m.) of cells with indicated mitochondrial morphologies in Drp1-/- 293T cells transfected with either scrambled siRNA (Ctr), hFis1 siRNA, Mfn1-Myc, Mfn2-Myc or OPA1-Myc in three independent experiments for each condition (n represents the number of cells analyzed).",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024
Mfn1: 55669
Mfn2: 9927
OPA1: 4976"
  },
  {
    "caption": "D. hFis1 interacts with Mfn1, Mfn2 and OPA1 as well as Drp1, but not with Dyn2 at endogenous levels following chemical crosslinking. Wild-type (WT) and Drp1-/- 293T cells were in vivo crosslinked with 1% formaldehyde (FA) and cell lysates were used for co-immunoprecipitation (IP) with Protein G beads bound to rabbit normal IgG (negative control) or rabbit anti-hFis1 antibody as indicated, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "G, H. Interaction of hFis1 with Mfn1/2 and with OPA1 are independent events. WT 293T cells were treated with control, OPA1 (G) or Mfn1 plus Mfn2 (H) siRNA, followed by in vivo crosslinking with 1% FA. Cell lysates were used for co-IP with Protein G beads bound to rabbit normal IgG (negative control) or rabbit anti-hFis1 antibody as indicated, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "Mfn1: 55669
Mfn2: 9927
OPA1: 4976"
  },
  {
    "caption": "I. Interactions between Mfn1/2 and OPA1 occur independent of hFis1. WT 293T cells were treated with control or hFis1 siRNA, followed by in vivo crosslinking with 1% FA. Cell lysates were used for co-IP with Protein G beads bound to mouse normal IgG (negative control) or mouse anti-OPA1 antibody as indicated, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "hFis1: 51024"
  },
  {
    "caption": "J. Interaction between Mfn1 and Mfn2 is not affected by hFis1 overexpression. 293T cells were transfected with empty vector or Myc-hFis1, followed by in vivo crosslinking with 1% FA. Cell lysates were used for co-IP with Protein G beads bound to mouse normal IgG or mouse anti-Mfn1 antibody, followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "Myc: 
hFis1: 51024"
  },
  {
    "caption": "B. Interaction of different hFis1 mutants with Mfns and OPA1. hFis1-/- 293T cells were transfected with the full-length and the truncated hFis1 mutants as indicated, followed by in vivo crosslinking with 1% FA. Cell lysates were used for co-IP with anti-Myc or anti-GFP agarose beads and the immunoprecipitates were analyzed by Western blotting with indicated antibodies.",
    "ncbi_link": "hFis1: 51024"
  },
  {
    "caption": "A, B. Representative confocal images of mitochondrial fusion in WT 293T polykaryons in cultures subjected to the PEG-based fusion assay in the presence or absence of exogenous hFis1. WT 293T cells stably expressing mitoGFP or mitoRFP were co-cultured, subsequently transfected with empty vector (control) or with Myc-hFis1 as indicated and then treated with PEG for cell fusion. Mitochondrial fusion is indicated by co-localization of mitoGFP and mitoRFP (i.e. yellow mitochondria). Left panel: empty vector transfected; right panel: Myc-hFis1transfected. Insets represent magnification of the boxed areas in upper panel (A). Quantitative analysis of the extent of mitochondrial fusion in individual hybrid cells was performed by the Pearson's correlation coefficient (PCC) in three independent experiments for each condition and data summarized in (B).",
    "ncbi_link": "Myc: 
hFis1: 51024"
  },
  {
    "caption": "C, D. Representative confocal images of mitochondrial fusion in WT 293T cells assessed by the mito-PAGFP-based fusion assay in the presence or absence of exogenous hFis1. WT 293T cells co-transfected with mito-PAGFP (0.5 µg), mito-DsRed (0.2 µg), and either empty vector (0.5 µg, the upper panel) or hFis1 (0.5 µg, the lower panel) were photoactivated in a small region of interest (ROI) (white circle, 3 µm diameter) in preactivation images of mitochondria seen by mito-DsRed (red). After photoactivation, sequential Z-stack images with photoactivated GFP (green) and mitochondrial marker (mito-DsRed) were collected at indicated time points using series of Z-sections from the top to the cell bottom with intervals between sections set to 0.5-0.75 μm (C). Mitochondrial fusion was quantified by analyzing changes in fluorescence intensity of photoactivated mito-PAGFP in ROIs at 40 sec, 15, 30, 45 min after photoactivation. The dilution rates (percentage) of the GFP fluorescence intensity at different time points were normalized by the fluorescence intensity at 40 sec after photoactivation (D).",
    "ncbi_link": "DsRed: 
PAGFP: 
hFis1: 51024"
  },
  {
    "caption": "E, F. Representative confocal images of mitochondrial fusion in WT 293T polykaryons in cultures subjected to the PEG-based fusion assay in the presence or absence of endogenous hFis1. Both WT 293T cells stably expressing mitoGFP or mitoRFP were transfected with scrambled siRNA (control siRNA) or hFis1-siRNA as indicated and then co-cultured and fused using PEG treatment. Left panel: control siRNA transfected; right panel: hFis1-siRNA transfected (E). Quantitative analysis of the mitochondrial fusion in individual hybrid cells was performed by the Pearson's correlation coefficient in three independent experiments and data summarized in (F).",
    "ncbi_link": "hFis1: 51024"
  },
  {
    "caption": "G, H. Representative confocal images of mitochondrial fusion in WT 293T cells assessed by the mito-PAGFP-based fusion assay in the presence or absence of endogenous hFis1. Scrambled siRNA or hFis1 siRNA treated cells were co-transfected with mito-PAGFP and mito-DsRed and were subsequently photoactivated (G) as described in (C). Mitochondrial fusion was quantified (H) as described in (D).",
    "ncbi_link": "DsRed: 
PAGFP: 
hFis1: 51024"
  },
  {
    "caption": "A, B. Representative confocal images of mitochondrial fusion in Drp1-/- 293T polykaryons in cultures subjected to the PEG-based fusion assay in the presence or absence of exogenous hFis1. Drp1-/- cells stably expressing mitoGFP or mitoRFP were co-cultured, subsequently transfected with empty vector (control) or Myc-hFis1 as indicated and then stimulated with PEG treatment for cell fusion, followed by immunostaining with anti-Myc antibody (green). Mitochondrial fusion was indicated by co-localization of mitoGFP and mitoRFP (i.e. yellow mitochondria). Left panel: empty vector transfected; right panel: Myc-hFis1 transfected. Insets represent magnification of the boxed areas in upper panel (A). Quantitative analyses for measuring the extent of mitochondrial fusion in individual hybrid cells were performed by the Pearson's correlation coefficient (PCC) in three independent experiments and summarized in (B).",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "C, D. Representative confocal images of mitochondrial fusion in Drp1-/- 293T cells assessed by the mito-PAGFP-based fusion assay in the presence or absence of exogenous hFis1. Drp1-/- cells co-transfected with mito-PAGFP, mito-DsRed, and either empty vector (the upper panel) or hFis1 (the lower panel) were photoactivated in a small region of interest (ROI) (white circle, 3 µm diameter) as indicated in preactivation images of mitochondria seen by mito-DsRed (red). After photoactivation, Z-stack images with photoactivated GFP (green) and mitochondrial marker (mito-DsRed) were collected at times 40 sec, 15, 30, 45 min as indicated (C). Mitochondrial fusion was quantified by analysis of changes in the fluorescence intensity of photoactivated mito-PAGFP in ROIs at 40 sec, 15, 30, 45 min after photoactivation. The dilution rates (percentage) of the GFP fluorescence intensity at different time points were normalized by the fluorescence intensity at 40 sec after photoactivation (D).",
    "ncbi_link": "DsRed: 
PAGFP: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "E, F. Representative confocal images of mitochondrial fusion in Drp1-/- 293T polykaryons in cultures subjected to the PEG-based fusion assay in the presence or absence of endogenous hFis1. Drp1-/- cells stably expressing mitoGFP or mitoRFP were transfected with scrambled siRNA (control siRNA) or with hFis1-siRNA as indicated and then co-cultured and fused by PEG treatment. Left panel: control siRNA transfected; right panel: hFis1-siRNA transfected (E). Quantitative analysis of extent of mitochondrial fusion in individual hybrid cells was performed by the Pearson's correlation coefficient (PCC) in three independent experiments and summarized in (F).",
    "ncbi_link": "Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "G, H. Representative confocal images of mitochondrial fusion in Drp1-/- 293T cells monitored by the mito-PAGFP-based fusion assay in the presence or absence of endogenous hFis1. Scrambled siRNA or hFis1 siRNA treated cells were co-transfected with mito-PAGFP and mito-DsRed and were subsequently photoactivated (G) as described in (C). Mitochondrial fusion was quantified by analysis of changes in the fluorescence intensity of photoactivated mito-PAGFP (H) as described in (D).",
    "ncbi_link": "DsRed: 
PAGFP: 
Drp1: 10059
hFis1: 51024"
  },
  {
    "caption": "A, B. GTP hydrolysis activities of Mfn1, Mfn2, Mfn2K109A and OPA1 in the presence or absence of recombinant GST-hFis1 or GST (negative control) were determined by measuring the concentration of free phosphate (Pi) released from GTP. Myc-tagged Mfn1, Mfn2, Mfn2K109A and OPA1 were transiently expressed separately in 293T cells and immunopurified by anti-Myc agarose beads. GTPase activities of immunopurified Myc-tagged Mfn1, Mfn2, Mfn2K109A and OPA1 were determined after treatment with or without recombinant GST-hFis1 or GST protein (A). The input levels of immunopurified Mfn1-Myc, Mfn2-Myc and OPA1-Myc (left panel) as well as recombinant GST-hFis1 (~42 kDa) and GST (~26 kDa) (right panel) were assessed by immunoblotting with indicated antibodies (B).",
    "ncbi_link": "Myc: 
Mfn1: 55669
Mfn2: 9927
OPA1: 4976"
  },
  {
    "caption": "C, D. GTP hydrolysis activities of Drp1 in the presence or absence of recombinant GST-hFis1 or GST (negative control) were determined as described in (A). Untagged WT Drp1 and Drp1Q34A were transiently expressed in Drp1-/- 293T cells and immunopurified by protein G beads pre-incubated with Drp1 antibody. GTPase activities of immunopurified Drp1 and Drp1Q34A were determined after treatment with or without recombinant hFis1 or GST protein (C). The input levels of immunopurified Drp1 and Drp1Q34A were assessed by immunoblotting with anti-Drp1 antibody (D).",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "E, F. GTP hydrolysis activities of Dyn2 in the presence or absence of recombinant GST-hFis1 or GST (negative control) were determined as described in (A). Endogenous Dyn2 in Drp1-/- 293T cells was immunopurified by protein G beads pre-incubated with anti-Dyn2 antibody. GTPase activity of immunopurified Dyn2 was determined after treatment with or without recombinant GST-hFis1 or GST protein (E). The input levels of immunopurified Dyn2 were assessed by immunoblotting with anti-Dyn2 antibody (F).",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "G. Summary of the effects of pro-fusion GTPases (Mfns and OPA1) on hFis1-induced mitochondrial fragmentation in Drp1-/- cells. Percentages (mean ± s.e.m.) of cells with indicated mitochondrial morphologies in Drp1-/- 293T cells co-expressing Myc-hFis1 and either empty vector, Mfn1-Myc, Mfn2-Myc or OPA1-Myc in three independent experiments. n represents the number of cells analyzed. Corresponding confocal images shown in Fig EV4.",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024
Mfn1: 55669
Mfn2: 9927
OPA1: 4976"
  },
  {
    "caption": "A. Ablation of OPA1 using CRISPR-Cas9 gene editing in Drp1-/- 293T cells was confirmed by Western blotting analysis.",
    "ncbi_link": "CRISPR: 
Drp1: 10059
OPA1: 4976
Cas9: 901176"
  },
  {
    "caption": "B. Confocal images of mitochondrial morphology in Drp1-/- (left panel) and Drp1/OPA1DKO 293T (right panel) cells. (Aggr/frag: aggregation/fragmentation of mitochondria; Bulb/tubular: bulb-like/tubular mitochondria).",
    "ncbi_link": "Drp1: 10059
OPA1: 4976"
  },
  {
    "caption": "C. Confocal images of mitochondrial morphology in Drp1/OPA1DKO 293T cells treated with the indicated siRNAs, combinations of siRNAs or with Myc-hFis1 plasmid (lower three panels) compared to mitochondrial morphology in Drp1-/- 293T cells overexpressing Myc-hFis1 or not (upper panel).",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024
OPA1: 4976"
  },
  {
    "caption": "D. Percentages (mean ± s.e.m.) of cells with indicated mitochondrial morphologies in Drp1-/- 293T cells transfected with empty vector or Myc-hFis1 plasmid, and in Drp1/OPA1DKO 293T cells treated with the indicated siRNA, combinations of siRNA or Myc-hFis1 plasmid. The data were collected from three independent experiments. Total cell numbers (n) used for statistical analysis are indicated for each condition.",
    "ncbi_link": "Myc: 
Drp1: 10059
hFis1: 51024
OPA1: 4976"
  },
  {
    "caption": "E. Knockdown of the indicated proteins by siRNA in Drp1/OPA1DKO 293T cells was confirmed by Western blotting analysis.",
    "ncbi_link": "Drp1: 10059
OPA1: 4976"
  },
  {
    "caption": "(B, Angiogenic capacity of  Oxct1  knockout cells in response to  ketone body treatment was analyzed using a spheroid-based sprouting assay. Spheroids were treated with media containing 30 mM D-β-hydroxybutyrate (βOHB), 30 mM acetoacetate (AcAc) or the respective controls (final concentration of reagents is diluted to approximately 10 %) for 48 hours. The average number of  sprouts per spheroid was quantified. Data are presented as mean ± SD. n=4; *, p<0.05; **, p<0.01; unpaired Student's t-test.",
    "ncbi_link": "Oxct1: 67041"
  },
  {
    "caption": "(a) Expression levels of Tcfeb mRNA in tissues isolated from 24-h-fasted (24 h starved) 6-week-old mice. Values are expressed as fold change relative to Tcfeb expression in mice fed ad libitum (Fed). Bars represent mean ± s.d. for n = 5 mice; *P≤0.05; **P≤0.01; ***P≤0.001.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(b) Representative β-gal staining of liver and kidney frozen sections isolated from fed and 24-h-fasted heterozygous Tcfeb- β-gal mice.",
    "ncbi_link": "β-gal: "
  },
  {
    "caption": "c) Time-course expression analysis of TFEB in wild-type HeLa cells, MEFs and hepatocytes after the addition of starvation media (time 0). Data represent mean ± s.d. for n = 3 independent experiments.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(d) Expression levels of transfected hTFEB-FLAG, Tcfeb- β-gal fusion transcript and endogenous Tcfeb mRNAs in MEFs isolated from control (+/+) and heterozygous Tcfeb- β-gal/+ mice. Data represent mean ± s.d. for n = 3 mice; *P≤0.05.",
    "ncbi_link": "β-gal: 
Tcfeb: 21425
TFEB: 7942"
  },
  {
    "caption": "(e) Time-course expression analysis of TFEB mRNA in control (Ctrl) or TFEB-overexpressing HeLa cells during fasting and re-feeding. Primers specific for the endogenous TFEB were used. Data represent mean ± s.d. for n = 3.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(f) Time-course expression analysis of Tcfeb mRNA in heterozygous Tcfeb- β-gal/+ or control MEFs during fasting and re-feeding. Specific primers for the endogenous Tcfeb were used. Data represent mean ± s.d. for n = 3 mice.",
    "ncbi_link": "β-gal: 
Tcfeb: 21425"
  },
  {
    "caption": "(g) Expression analysis of Tcfeb mRNA in heterozygous Tcfeb- β-gal/+ or control hepatocytes in fed and after 24 h fasting. Data represent mean ± s.d. for n = 3 mice.",
    "ncbi_link": "β-gal: 
Tcfeb: 21425"
  },
  {
    "caption": "(h) ChIP analysis from liver of mice fed ad libitum or 24 h fasted. The CLEAR elements in the first intron of Tcfeb genomic DNA are shown as numbered black rectangles as indicated in Supplementary Table S1. Red rectangles represent exons, and the ATG indicates the first codon (from the mouse Tcfeb isoform b). The histogram shows the amount of immunoprecipitated DNA as detected by quantitative PCR assay. Values were normalized to the input and plotted as relative enrichment over a mock control. Data represent mean ± s.d of 3 independent experiments.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(a) ChIP analysis from liver of mice fed ad libitum (fed) or 24 h-fasted (starved). CLEAR sites in the promoter region of Pgc-1α are indicated by squares. Numbers indicate the distance (bp) of the binding element from the start codon. Bar graphs show the amount of immunoprecipitated DNA as detected by quantitative PCR assay. Values were normalized to the input and plotted as relative enrichment over a mock control. Bar graphs represent mean ± s.d of 3 independent experiments, *P≤0.05; **P≤0.01.",
    "ncbi_link": "Pgc-1α: 19017"
  },
  {
    "caption": "(c) Luciferase activity was measured after transfecting increasing amounts of TFEB-FLAG in combination with Pgc-1α WT or Pgc-1α DEL plasmids. Bar graphs represent mean ± s.d. of n = 3independent experiments, ****P≤0.0001 compared with mock transfected cells.",
    "ncbi_link": "Pgc-1α: 19017
TFEB: 21425"
  },
  {
    "caption": "(d) Luciferase activity was measured in cells stably overexpressing TFEB cultured in normal and starved media. Bar graphs represent mean ± s.d. of n = 3independent experiments **P≤0.01 compared with mock transfected cells.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(e) Quantification of mRNA levels of PGC1α in liver and hepatocytes from control, HDAd-TFEB and Tcfeb-LiKO (liver KO) mice treated as indicated. Bar graphs show mean ± s.d. for n = 4 mice. *P≤0.05; **P≤0.01.",
    "ncbi_link": "PGC1α: 19017
Tcfeb: 21425
TFEB: 7942"
  },
  {
    "caption": "(f) Expression analysis of TFEB target genes in liver of mice with indicated genotypes. Bar graphs show mean ± s.d. for n = 3 mice. *P≤0.05;**P≤0.01; ***P≤0.001.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(g) Expression analysis of PGC1α/PPARα target genes in liver from either fasted or fed mice with indicated genotypes. Bar graphs show mean ± s.d. for n = 4. *P≤0.05; **P≤0.01 compared with the respective controls (fed or fasted).",
    "ncbi_link": "PPARα: 19013
PGC1α: 19017"
  },
  {
    "caption": "(a) Oil red O staining of liver sections isolated from mice with the indicated genotype fed ad libitum and 24 h fasted. Original magnification ×40. (b) Toluidin blue staining of liver sections isolated from fed and 24-h-fasted Tcfeb-LiKO and control mice (Tcfeb flox/flox mice). Arrows indicate lipid droplets. Original magnification ×100.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(d) The oxygen consumption rate (OCR) in primary hepatocytes isolated from control and Tcfeb-LiKO mice was measured with an XF24 analyser (Seahorse) before and after the addition of palmitic acid (0.2 mM) conjugated with BSA. The vertical red line indicates the time at which palmitate was added to cells. Values are mean ± s.d. for 3 independent experiments *P≤0.05.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(e,f) Total FFA (e) and glycerol (f) in the serum isolated from 6-h-fasted Tcfeb-LiKO and control mice. Values are mean ± s.d. (n = 5 mice per group) *P≤0.05 compared with controls.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(g) Total serum ketones in fed and fasted Tcfeb-LiKO and control mice. Bars are mean ± s.d. for n = 10 mice per group. **P≤0.01 compared with fed control mice.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(d) Toluidin blue staining of liver sections isolated from Atg7-LiKO mice injected with HDAd-Ctrl or HDAd-TFEB vector.",
    "ncbi_link": "Atg7: 74244
TFEB: 7942"
  },
  {
    "caption": "(c-i) Serum metabolic profile in HDad-TFEB mice compared with control mice.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(a) Body weight curves of male mice fed with the high-fat diet (HFD; 40% calories from fat) for 10 weeks starting from 5 weeks of age (0 on the x axis). Mice were injected with HDAd-TFEB either 1 week before (early inj), or 4 weeks after, (late inj) being placed on the high-fat diet, as indicated by the arrows. Values are represented as percentages of weight increase. Ctrl, control. (b) Whole-body composition analysis (EchoMRI) of the same mice as in a after 10 weeks of the high-fat diet. In a,b n = 10 mice per group; bars represent mean ± s.d. *P≤0.05;**P≤0.01; ***P≤0.001 compared with control high-fat diet group.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(c-f) Total serum insulin, leptin, triglyceride and cholesterol levels in control and HDAd-TFEB mice kept on the high-fat diet for 10 weeks. Value are mean ± s.d. n = 10 add per group. *P≤0.05; ****P≤0.0001 compared with control. (g-i) Glucose and insulin tolerance tests in control and HDAd-TFEB mice challenged with the high-fat diet for 10 weeks.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(a) hlh-30 quantitative rtPCR showing increased expression of the C. elegans TFEB gene hlh-30 over a time course of starvation in wild-type animals followed by a rapid decrease to the basal level following re-feeding of the animals (mean±s.e.m. of n = 3). *P≤0.05 (t-test, compared with wild-type at t = 0 h).",
    "ncbi_link": "hlh-30: 177157
TFEB: 7942"
  },
  {
    "caption": "(b) hlh-30 3' UTR quantitative rtPCR showing expression of hlh-30 after 12 h starvation in wild-type and hlh-30(tm1978) animals (mean±s.e.m. of n = 3). *P≤0.05 (t-test, compared with wild-type starved).",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(d-g) Representative micrographs of wild-type and hlh-30 animals after 8 h starvation and stained with oil red O.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(h-k) Representative TEMs of wild-type and hlh-30 animals after 24 h starvation. IEC, intestinal epithelial cell; EPI, epidermis; BB, brush border; GON, gonad; BWM, body wall muscles, aj, apical junction; ld, lipid droplet. Scale bar, 2 μm.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(l) Quantitative rtPCR of starvation-induced genes in wild-type and hlh-30 animals after 12 h starvation (means ± s.e.m of n = 3). *P≤0.05; **P≤0.01; ***P≤0.001 (t-test, compared with wild-type starved).",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(m,n) hlh-30 is required for starvation-induced lifespan extension. One representative experiment of 2 independent trials; error bars represent mean±s.e.m. Median survival (MS) (wild-type fed) = 10 d; MS (wild-type starved) = 17 d, P0.0001 versus fed using the Log-rank test; MS (hlh-30 fed) = 7 d; MS (hlh-30 starved) = 9 d, P0.0001 versus fed.",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(o) L1 arrest assay showing survival of wild-type and hlh-30 starved animals relative to non-starved conditions (mean±s.e.m. of n = 3). ***P≤0.001 (t-test, compared with wild-type starved).",
    "ncbi_link": "hlh-30: 177157"
  },
  {
    "caption": "(A) HEK293A cell lines stably expressing GFP, GFP-WIPI1a, and GFP-WIPI2b were incubated in full medium (F) or starvation medium (EBSS) (S) for 2 hr before being used for GFP-TRAP pull-down.",
    "ncbi_link": "WIPI1a: 55062
WIPI2b: 26100"
  },
  {
    "caption": "(C) WT or Atg16L1Δ/Δ MEFs in fed medium or starved for 2 hr in EBSS were fixed and labeled with an anti-WIPI2 antibody. Scale bars, 10 μm.(D) WIPI2 puncta in (C) were counted, and a statistical analysis of WIPI2 puncta was performed using an unpaired Student's t test. ∗p < 0.05. SEM for n = 3.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(E-H) CLEM (correlative light and electron microscopy) of endogenous WIPI2 in Atg16L1Δ/Δ MEFs.(E) Merged phase and confocal section of Atg16L1Δ/Δ cells labeled with anti-WIPI2 antibody. Scale bar, 10 μm.(F) Low-magnification TEM of cell in (E). Scale bar 10μm.(G and H) High magnification of boxed regions in (E) and (F). Top box and bottom box indicate panels (G) and (H), respectively. Arrows indicate open phagophores. M, mitochondria; ER, endoplasmic reticulum. Scale bars, 1 μm (G) and 0.5 μm (H).",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(B) Untransfected (UN) or FLAG-Atg16L1 full-length (FL), 79-623, or 1-265 constructs were expressed in HEK293A cells stably expressing GFP-WIPI2b and immunoprecipitated using GFP-TRAP. Tags were visualized by immunoblotting. I, input; UB, unbound.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(C) GFP, CFP-Atg5, GFP-WIPI1a, and GFP-WIPI2b were transiently expressed in HEK293A cells. GFP-tagged proteins were isolated using GFP-TRAP and incubated with in vitro translated 35S-labeled FLAG-Atg16L1 constructs 1-265, 1-242, 1-230, and 1-207 before washing and analysis by autoradiography. Protein expression was validated by immunoblot (bottom panel).",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(B) Lysates from HEK293A cells transfected with GFP-WIPI2b were mixed with lysates from HEK293A cells transfected with FLAG-Atg16L2, FLAG-Atg16L1, or Flag-Atg16L1 mutants, immunoprecipitated, and analyzed by immunoblotting.(C) Statistical analysis of FLAG-Atg16L1 binding in (B) was performed by Student's t test. SEM for n = 4. ∗p < 0.05.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(D) Cell lysates from HEK293A cells transiently expressing FLAG-Atg16L2, FLAG-Atg16L1, or FLAG-Atg16L1 mutants were subjected to immunoprecipitation using FLAG M2 agarose beads. Protein complexes were analyzed using immunoblotting.(E) Statistical analysis of FIP200 binding in (D) was performed by Student's t test. SEM for n = 3. ∗p < 0.05.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(F) WIPI2 was immunoprecipitated from lysates from WT or FIP200−/− MEFS after treatment with 0.5 mM DSP. Bound Atg16 and Atg12-5 were detected by immunoblotting.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(G) HEK293 cells stably expressing GFP-WIPI2b were and transiently transfected either FLAG-Atg16L1 WT, E226R E230R (ERER), or D237R D239R (DRDR). Bound and input (bottom) were analyzed by immunoblotting.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(A) Lysates from HEK293A cells transiently expressing GFP, GFP-WIPI1a, GFP-WIPI2a, GFP-WIPI2b, or GFP-WIPI2b FTTG mutant were used for GFP-Trap. Endogenous Atg16L1 binding was analyzed by immunoblot.(B) Statistical analysis of (A) was performed by one-way ANOVA with Tukey's posttest. SEM for n = 3. ∗p < 0.05.",
    "ncbi_link": "WIPI2b: 26100"
  },
  {
    "caption": "(D) GFP-Trap from HEK293A cells transiently expressing GFP, GFP-WIPI1a, GFP-WIPI2b, GFP-WIPI2b R108E, GFP-WIPI2b R125E, or GFP-WIPI2b R108E R125E was mixed with in vitro translated 35S-labeled FLAG-Atg16L1 and analyzed by autoradiography.",
    "ncbi_link": "WIPI2b: 26100"
  },
  {
    "caption": "(E) Lysates from HEK293A cells transiently expressing GFP, GFP-WIPI2b, GFP-WIPI2b ΔCT, GFP-WIPI2a, GFP-WIPI1a, or GFP-WIPI1a ΔCT were used for GFP-Trap. Endogenous Atg16L1 binding was analyzed by immunoblot.(F) Statistical analysis of (E) was performed by one-way ANOVA with Tukey's posttest. SEM for n = 2. ∗p < 0.05.",
    "ncbi_link": "WIPI1a: 55062
WIPI2b: 26100"
  },
  {
    "caption": "(G) Lysates from HEK293A cells transiently expressing GFP-WIPI2b WT, GFP-WIPI2b R108E, R125E, or R108E R125E were mixed with lysates from HEK293A cells transiently expressing FLAG-Atg16L1 WT, E226R, E230R, or E226R E230R in all possible permutations. Protein complexes from mixed lysates were immunoprecipitated using GFP-Trap, followed by immunoblot analysis.(H) Statistical analysis of (G) was performed by one-way ANOVA with Tukey's posttest. SEM from n = 3. ∗p < 0.05.",
    "ncbi_link": "Atg16L1: 55054
WIPI2b: 26100"
  },
  {
    "caption": "(I) CLEM analysis of HEK293 cells treated with siRNA to WIPI2 were transfected with GFP-WIPI2b RERE and starved in EBSS. Bright-field image (top), GFP-WIPI2 RERE signal (middle), TEM of selected cell (bottom). Boxed area shown in (J). Scale bars represent 10 μM for bright-field and confocal and 5 μM for TEM.(J) High-magnification TEM of boxed area in (I). Arrows indicate open phagophores in the vicinity of ER and mitochondria (M), which contain GFP-WIPI2b RERE. See also Figures S4 and S5 and Table S1.",
    "ncbi_link": "WIPI2: 26100
WIPI2b: 26100"
  },
  {
    "caption": "(A) GFP, siRNA-resistant GFP-WIPI2b, or GFP-WIPI2b RERE was expressed in HEK293A cells treated for 72 hr with either RISC-free (RF) or WIPI2 siRNA. Cells were left in full medium (F) or starved for 2 hr with EBSS (S) or EBSS with BafA (B) before immunoblot analysis.(B) Statistical analysis of (A). SEM for n = 3. Statistical analysis was performed by one-way ANOVA with Tukey's posttest. ∗p < 0.05.",
    "ncbi_link": "WIPI2b: 26100"
  },
  {
    "caption": "(C) GFP, siRNA-resistant GFP-WIPI2b, GFP-WIPI2b RERE, GFP-WIPI2b FTTG, or GFP-WIPI2b FTTG RERE was expressed in HEK293A cells treated for 72 hr with WIPI2 siRNA. Cells were left in full medium (F) or starved for 2 hr with EBSS (S) or EBSS with BafA (B) before immunoblot analysis.(D) Statistical analysis of (C) was performed by one-way ANOVA with Tukey's posttest. The SEM for LC3 (n = 2) and p62 (n = 4) are shown. ∗p < 0.05.",
    "ncbi_link": "WIPI2: 26100
WIPI2b: 26100"
  },
  {
    "caption": "(E) siRNA-resistant GFP-WIPI2b, GFP-WIPI2b RERE, GFP-WIPI2b FTTG, or GFP-WIPI2b FTTG RERE was expressed in HEK293A cells treated for 72 hr with WIPI2 siRNA. Cells were starved in EBSS for 2 hr without or with BafA, fixed, and labeled, and LC3 was visualized by confocal microscopy. Scale bars, 10 μm.(F) Quantification of WIPI2 puncta per cell from (E). SEM from 10 cells per condition; ∗∗∗p < 0.001 using one-way ANOVA.(G) Statistical analysis of LC3 puncta from (E) with GFP control (not shown in E). SEM for n = 3. Statistical analysis was performed by one-way ANOVA with Dunn's posttest t test. ∗p < 0.05. See also Table S1.",
    "ncbi_link": "WIPI2: 26100
WIPI2b: 26100"
  },
  {
    "caption": "(E) CLEM of MCF7 cells expressing GFP-LC3 and mCherry-WIPI2b CAAX. Bright-field and confocal image merged (left), confocal of expressing cell (middle), low-magnification TEM of cell of interest (right). Boxed area indicates plasma membrane region showing colocalization of GFP-LC3 and mCherry-WIPI2b. Scale bar, 10 μm (n = 3).(F) High-magnification TEM showing plasma membrane region boxed in (E). Magnified insets, in top right, show small vesicular clusters under the plasma membrane detected in mCherry-WIPI2b CAAX, GFP-LC3 expressing cells but not in untransfected cells from a control experiment.",
    "ncbi_link": "WIPI2b: 26100"
  },
  {
    "caption": "(G) HEK293A cells treated with either RISC-free (RF), Atg16L1 siRNA, or FIP200 siRNA for 72 hr before transfection with HA-WIPI2b-CAAX were incubated in full medium (F), EBSS (S), or EBSS with wortmannin (W) for 2 hr before immunoblot analysis. Please note that all WIPI2 constructs are FTTG mutants. See also Figure S6 and Table S1.",
    "ncbi_link": "Atg16L1: 55054
FIP200: 12421"
  },
  {
    "caption": "(A) Atg16L1Δ/Δ MEFs were transiently transfected with either mock, FLAG-tagged Atg16L1 WT, ERER, or DRDR. After 2 hr in EBSS, cells were fixed and labeled with anti-LC3 and anti-FLAG antibodies and visualized by confocal microscopy. Scale bars, 20 μm.(B) Statistical analysis of (A) was performed using one-way ANOVA with Dunn's posttest. ∗p < 0.05. SEM for n = 3.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(C) Atg16L1Δ/Δ MEFs were transiently transfected with either mock, FLAG-tagged Atg16L1 WT, E226R E230R (ERER), or D237R D239R (DRDR) before analysis by immunoblotting.(D) Statistical analysis of (C) was performed by one-way ANOVA with Tukey's post hoc test. SEM for n = 3. ∗p < 0.05.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(E) HEK293A cells were treated with either RISC-free control or WIPI2 siRNA before infection with Salmonella (moi = 100) for 1 hr, labeled with anti-LC3, WIPI2, and p62 antibodies, and followed by confocal analysis. Scale bars, 5 μm.(F) Statistical analysis for (E) was performed using an unpaired Student's t test. ∗p < 0.05. SEM for n = 3.",
    "ncbi_link": "WIPI2: 26100"
  },
  {
    "caption": "(G) Atg16L1Δ/Δ MEFs were transiently transfected with FLAG-Atg16L1 WT, FLAG-Atg16L1 ERER, or FLAG-Atg16L2 DRDR 24 hr before being infected with Salmonella (moi = 25) for 1 hr, labeled with anti-LC3, anti-p62, and anti-FLAG antibodies, and followed by analysis by confocal microscopy. Scale bars, 5 μm.(H) Statistical analysis of (G) was performed by one-way ANOVA with Dunn's post hoc test. SEM for n = 4. ∗p < 0.05. See also Figure S7.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "(B) RAW 264.7 macrophages expressing the lipid biosensor for PI(4,5)P2, PH-Plcδ-RFP (in red), were left uninfected or were infected with live GFP-expressing S. aureus USA300 (in green) for 8 h prior to fixation. The macrophage plasmalemma and extracellular bacteria are indicated by Cy5-conjugated wheat germ agglutinin (WGA, in blue). As a control, to demonstrate displacement of PH-Plcδ-RFP from the macrophage membrane, transfected cells were treated with 10 µM ionomycin in the presence of 1 mM CaCl2 for 20 min prior to fixation. These images are representative of three independent experiments.",
    "ncbi_link": "RFP: 
Plcδ: 24655"
  },
  {
    "caption": "(A) Growth of wild-type S. aureus USA300 or a purK mutant. The data are the mean ± standard deviation of the end point optical density measured at 18 h at 600nm for each strain in RPMI. Additives are indicated on the x axis and were either 5% (v/v) FBS, 50 μM IMP, 10 μM PIK-III and 100 μM Dynasore or an equivalent volume of DMSO. Each symbol represents a biological replicate of S. aureus and the data derive from three independent experiments. Statistical significance was determined by a one-way ANOVA with a Holm-Sidak's multiple comparison test. n.s. indicates not significant, *** indicates p<0.0001.",
    "ncbi_link": "purK: 45574301"
  },
  {
    "caption": "(B) The graph depicts the fold change in bacterial burden for RAW 264.7 macrophages infected with purK S. aureus. Macrophages were left untreated or were exposed to 50 μM IMP or 50 μM IMP after pretreatment with PIK-III and Dynasore which were maintained throughout the infection. The data are the mean ± standard deviation of the burden at 10 h post-infection normalized to the burden at 1.5h post-infection prior to the addition of IMP. Each symbol represents a single biological replicate of S. aureus and derive from three independent experiments. Significance was determined by one-way ANOVA with a Turkeys multiple comparison test. *p<0.05, **p<0.01.",
    "ncbi_link": "purK: 45574301"
  },
  {
    "caption": "(C, D) The ability of purK S. aureus to grow in an IMP-dependent manner within primary bone marrow-derived macrophages is shown. (C) Fluorescence micrographs depicting purK replication analyzed by fluorescence proliferation assay where non-replicating bacteria are both GFP and proliferation dye positive. In contrast, replicating bacteria (white arrows) are only GFP positive. The top row depicts purK infected BMDMs without IMP whereas the bottom row depicts macrophages carrying purK S. aureus in the presence of 50 μM IMP. Images were acquired at 12 h post-infection and are representative of three independent experiments. Scale bars equal 10 μm. (D) The fraction of macrophages containing replicating bacteria was determined for purK infected BMDMs. Each data point represents a biological replicate (n=8) and derived from three independent experiments. The data shown are the mean ± standard deviation where the data were normalized to the no IMP condition. ** indicates p<0.01 as determined by an unpaired two-tailed t-test with a Wilcoxon matched pairs test.",
    "ncbi_link": "purK: 45574301"
  },
  {
    "caption": "A, B, C. Correlations between the levels of single stress indicators and correction of GAA activity  by rhGAA in 6 different PD fibroblasts. ROS production and lipid peroxidation inversely correlate with the  GAA levels attained in cells after incubation with rhGAA for 4 hours. The analysis of correlation was calculated, and the coefficient of Pearson is indicated. D ",
    "ncbi_link": "GAA: 2548"
  },
  {
    "caption": "C. GAA activity in tissues from the Gaa  KO mouse after treatment with rhGAA alone (black bars) (n of mice = 10) and with co-dosing of rhGAA and 2 gr/Kg/day NAC (n of mice  =7, dark grey bars). Data presented as mean ± SD. Values obtained in tissues treated with rhGAA alone for each treatment are taken as 100. A Student's t-test was applied to compare the results in each of the tissues. D. GAA activity in tissues from the Gaa KO  mouse after treatment with rhGAA alone (black bars) (n of mice =4) and with co-dosing of rhGAA and 100 mg/Kg/day IDE (n of mice =6, light grey bars). Data presented as mean ± SD. Values obtained in tissues treated with rhGAA alone for each treatment are taken as 100. A Student's t-test was applied to compare the results in each of the tissues. E ",
    "ncbi_link": "Gaa: 14387
GAA: 2548"
  },
  {
    "caption": "E, F. Western Blot  analyses of  GAA and quantitative analyses of the enzyme in representative tissues from the  Gaa  KO mouse after treatment with rhGAA alone (n of mice =2) or in combination with NAC (n of mice =3) (E) or IDE (n of mice =3) (F). In F Data are presented as mean ± SD.",
    "ncbi_link": "Gaa: 14387
GAA: 2548"
  },
  {
    "caption": "G. Glycogen  assay in tissues from the  Gaa  KO mouse  after treatment with rhGAA alone (n of mice = 3) or in combination with NAC (n of mice  = 3). H. Glycogen  assay in tissues from the Gaa  KO mouse after treatment with rhGAA alone (n of mice =4) or in combination with  IDE  (n of mice = 6). Data information: i data are presented as mean ± SD. Values obtained in tissues treated with rhGAA alone for each treatment are taken as 100. A Student's t-test was applied to compare the results in each tissue.  ",
    "ncbi_link": "Gaa: 14387
GAA: 2548"
  },
  {
    "caption": "(A) Top panel: Scheme illustrating the tetracycline inducible Flp-In 293 system that controls the expression of HA-IKKε or HA-GFP. Bottom panel: Representative western blot showing induced expression of HA-IKKε in Flp-In 293 cells treated with doxycycline (Dox, 50 ng/ml) for 16 hours compared to endogenous IKKε in T47D, MDA-MB-231 and MDA-MB-468 breast cancer cell lines.",
    "ncbi_link": "GFP.: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(B) Heatmap and hierarchical clustering of metabolite concentrations in Flp-In 293 HA-GFP and Flp-In 293 HA-IKKε cells treated with doxycycline (Dox, 50 ng/ml, 16 hours) (n=5 technical replicates).",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(C) Serine production from glucose (serine m+3, 13C6-glucose labelling, left panel) and glutamine (serine m+1, 15N2-glutamine labelling, right panel) in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours) metabolite levels were normalised to the internal standard HEPES.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(E) Contribution of pyruvate and glucose-derived carbon to TCA cyle metabolites in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours). (n=5 technical replicates). metabolite levels were normalised to the internal standard HEPES.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(F) Fractional enrichment of serine, malate and citrate 13C-isotopologues in Flp-In 293 HA-GFP and Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours) (n=5 technical replicates).",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(G) Fractional enrichment of the serine 15-N-isotopologue in Flp-In 293 HA-GFP and Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours). m+1 shows the naturally occurring 13C isotopologue (n=5 technical replicates). metabolite levels were normalised to the internal standard HEPES.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "Representative western blot showing level of IKKε in IKBKE (IKKε)-silenced (A) T47D breast cancer cell lines.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "Representative western blot showing level of IKKε in IKBKE (IKKε)-silenced (B) MDA-MB-468 breast cancer cell lines.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(C-D) Heatmap and hierarchical clustering of metabolite concentrations in (C) IKBKE (IKKε)-silenced T47D cells and (D) IKBKE (IKKε)-silenced MDA-MB-468 cells (n=5 technical replicates). metabolite levels were normalised to the internal standard HEPES.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(E) Glycine production, representative of serine production, from glutamine (glycine m+1, 15N-glutamine labelling) and glucose (glycine m+2, 13C6-glucose labelling), and contribution of pyruvate and glucose-derived carbon to TCA cycle metabolites (citrate m+2, malate m+2, 13C6-glucose labelling) in IKBKE (IKKε)-silenced T47D cells. (n=5 technical replicates). metabolite levels were normalised to the internal standard HEPES.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(F) Serine production from glutamine (serine m+1, 15N-glutamine labelling), and serine and glycine production from glucose (glycine m+2, serine m+3, 13C6-glucose labelling) as well as contribution of pyruvate and glucose-derived carbon to TCA cycle metabolites (malate m+2, 13C6-glucose labelling) in IKBKE (IKKε)-silenced MDA-MB-468 cells.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(A) Basal oxygen consumption in Flp-In 293 HA-IKKε wt, Flp-In 293 HA-IKKε KD-m and Flp-In 293 HA-IKKε UbLD-m cells following treatment with doxycycline (Dox, 16 hours), measured using Oroboros high resolution respirometry. Data are normalised to non-treated control cells.",
    "ncbi_link": "HA: 
IKKε: 9641"
  },
  {
    "caption": "(B) Average TMRM staining intensity in Flp-In 293 HA-IKKε wt, Flp-In 293 HA-IKKε KD-m and Flp-In 293 HA-IKKε UbLD-m expressing cells induced by doxycycline (Dox, 16 hours). Data are normalised to non-treated control cells.",
    "ncbi_link": "HA: 
IKKε: 9641"
  },
  {
    "caption": "(C) Basal mitochondrial oxygen consumption rate (OCR) in a panel of IKBKE (IKKε)-silenced breast cancer cell lines, measured using Seahorse XF96e or XF24 analysis.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(D) OCR in mitochondria isolated from Flp-In 293 HA-GFP or HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours), measured using Oroboros high resolution respirometry.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(F) Representative western blot showing l­evel of IKKε in three independent single cell clones of Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells following treatment with doxycycline (100 ng/ml, 16 hours).",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(G) Relative pyruvate dehydrogenase (PDH) activity in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml, 16 hours).",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(H) Average TMRM staining intensity in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (Dox) and DCA (both for 16 hours). Data are normalised to non-treated Flp-In 293 HA-IKKε cells.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(I) Basal OCR in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml) in combination with dichloroacetate (DCA) for 16 hours, measured using Oroboros high resolution respirometry.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(J) Basal OCR in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (50 ng/ml) in combination with pyruvate deprivation for 16 hours, measured using Oroboros high resolution respirometry.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(A) Representative western blot showing level of ATF4 in ATF4-silenced Flp-In 293 HA-IKKε cells treated with doxycycline (16 hours).",
    "ncbi_link": "HA: 
ATF4: 468
IKKε: 9641"
  },
  {
    "caption": "(B) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (Dox) for 16 hours. Data are expressed as fold changes, relative to levels in non-treated Flp-In 293 HA-GFP cells and normalised to β-Actin (n=4 biological replicates)",
    "ncbi_link": "β-Actin: 
GFP: 
HA: 
IKKε: 9641
PHGDH: 26227
PSAT1: 29968
PSPH: 5723"
  },
  {
    "caption": "(C) Representative western blot showing levels of IKKε, IRF3, phosphorylated IRF3 (S396) and SBP enzymes in Flp-In 293 HA-GFP or Flp-In 293 HA-IKKε cells treated with doxycycline (Dox) for 16 hours.",
    "ncbi_link": "GFP: 
HA: 
IKKε: 9641"
  },
  {
    "caption": "(D) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in ATF4-silenced Flp-In 293 HA-IKKε cells treated with doxycycline (Dox) for 16 hours. Data are expressed as fold changes, relative to levels in a non-silenced, non-treated control, and normalised to β-Actin (n=5 biological replicates).",
    "ncbi_link": "β-Actin: 
HA: 
ATF4: 468
IKKε: 9641
PHGDH: 26227
PSAT1: 29968
PSPH: 5723"
  },
  {
    "caption": "(E) Representative western blot showing levels of IKKε, PHGDH, PSAT1 and PSPH in ATF4-silenced Flp-In 293 HA-IKKε cells treated with doxycycline (Dox) for 16 hours.",
    "ncbi_link": "HA: 
ATF4: 468
IKKε: 9641"
  },
  {
    "caption": "(A) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in a panel of IKBKE (IKKε)-silenced breast cancer cell lines. Data are expressed as fold changes, relative to levels in a non-silenced control of each cell line and normalised to β-Actin (n≥3 biological replicates).",
    "ncbi_link": "β-Actin: 
IKBKE: 9641
IKKε: 9641
PHGDH: 26227
PSAT1: 29968
PSPH: 5723"
  },
  {
    "caption": "(B) Representative western blot showing levels of IKKε and the SBP enzymes in IKBKE (IKKε)-silenced ZR-75-1, T47D, MDA-MB-468 and MCF7 breast cancer cell lines.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(C-E) Levels of the SBP enzymes in a panel of IKBKE (IKKε)-silenced breast cancer cell lines. (C) PHGDH, (D) PSAT1 and (E) PSPH levels in indicated cell lines normalised to Vinculin. Densitometry analysis quantified single sample density as a percentage of total blot density per cell line prior to vinculin normalisation (n≥3 biological replicates).",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(F) qRT-PCR analysis of PHGDH, PSAT1 and PSPH mRNA levels in ATF4-silenced ZR-75-1, T47D and MDA-MB-468 breast cancer cell lines. Data are expressed as fold changes, relative to levels in non-silenced control cells and normalised to β-Actin (n=3 biological replicates).",
    "ncbi_link": "β-Actin: 
ATF4: 468
PHGDH: 26227
PSAT1: 29968
PSPH: 5723"
  },
  {
    "caption": "(G) Representative western blot showing levels of PHGDH, PSAT1 and PSPH in ATF4-silenced ZR-75-1, MDA-MB-468, MDA-MB-231, T47D and HCC1143 breast cancer cell lines.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "(A) Correlation of change in OCR (ΔOCR) in a panel of IKBKE (IKKε)-silenced breast cancer cell lines (from Fig. 3C) and the change in cell confluency (Δconfluency) upon treatment of the panel of cell lines with NCT502 (from Fig. EV5A).",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(B) Correlation of ΔOCR in a panel of IKBKE (IKKε)-silenced breast cancer cell lines (from Fig. 3C) and the Δconfluency upon treatment of the panel of cell lines with 6-Diazo-5-oxo-L-norleucine (DON) (from Fig. EV5C).",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641"
  },
  {
    "caption": "(C) Association between IKBKE (IKKε) and PSAT1 mRNA overexpression evaluated by a chi-squared independence test. The + sign indicates samples with significant (p<0.05) overexpression of IKBKE or PSAT1. Number and percentage of samples, as well as the Chi-square values are shown.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641
PSAT1: 29968"
  },
  {
    "caption": "Expression of IKBKE (IKKε) and the SBP enzymes PSAT1, in the METABRIC dataset. Samples were stratified by Pam50 intrinsic subtypes and ER status. Brown-Forsythe and Welch ANOVA test with unpaired t-test with Welch correction were applied. *p<0.05, **p< 0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "IKBKE: 9641
IKKε: 9641
PSAT1: 29968"
  },
  {
    "caption": "Expression of SBP enzymes PHGDH and PSPH in the METABRIC dataset. The expression of a proliferation related gene set and ATF4 are also shown. Samples were stratified by Pam50 intrinsic subtypes and ER status. Brown-Forsythe and Welch ANOVA test with unpaired t-test with Welch correction were applied. *p<0.05, **p< 0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "ATF4: 468
PHGDH: 26227
PSPH: 5723"
  },
  {
    "caption": "(J) Association between IKBKE (IKKε) and ATF4 mRNA overexpression evaluated by chi-squared independence test. The + sign indicates samples with significant (p<0.05) overexpression of IKBKE or PSAT1. Number and percentage of samples, as well as the Chi-square values are shown.",
    "ncbi_link": "ATF4: 468
IKBKE: 9641
IKKε: 9641
PSAT1: 29968"
  },
  {
    "caption": "(K, L) Correlation of IKBKE (IKKε) and PSAT1 (K) or IKBKE (IKKε) and ATF4 (L) expression in the ER negative sample subset.",
    "ncbi_link": "ATF4: 468
IKBKE: 9641
IKKε: 9641
PSAT1: 29968"
  },
  {
    "caption": "a. Sorted CD4+CD25hiCD127- Tregs were stimulated in the presence of vehicle (white dots) or either SF1670 (first row), SC-79 (second row), 740 Y-P (third row) or AS1842856 (fourth row, black dots) for 3 days and IFNG and TBX21 gene expression was examined every 24 hours. Statistical analysis of n=4 independent experiments performed.",
    "ncbi_link": "IFNG: 3458
TBX21: 30009"
  },
  {
    "caption": "f. IFNG and TBX21 gene expression on Tregs transduced with a Foxo1 or Foxo3 shRNA as compared to the NT-shRNA control, measured at day 6 after 4 hours of stimulation with PMA and ionomycin.",
    "ncbi_link": "Foxo1: 2308
Foxo3: 2309
IFNG: 3458
TBX21: 30009"
  },
  {
    "caption": "g. Percentage of suppression of CFSE-labeled Tresp proliferation co-cultured with Tregs transduced with a non-target (white dots), Foxo1 (left diagram, black dots) or Foxo3 shRNA (right diagram, black dots) at different Treg:Tresp ratios (n=4). *p < 0.05, **p < 0.005, ***p < 0.0005.",
    "ncbi_link": "Foxo1: 2308
Foxo3: 2309"
  },
  {
    "caption": "Sorted Tregs were stimulated with anti-CD3, anti-CD28, IL-2 and shRNA specific for AKT1, AKT2, AKT3, or non-target control and resorted based on GFP expression at day 5. a. IFNG, TBX21, IL10, FOXP3 gene expression after sort at day 5 (n=5).",
    "ncbi_link": "AKT1: 207
AKT2: 208
AKT3: 10000
FOXP3: 50943
IFNG: 3458
IL10: 3586
TBX21: 30009"
  },
  {
    "caption": "Sorted Tregs were stimulated with anti-CD3, anti-CD28, IL-2 and shRNA specific for AKT1, AKT2, AKT3, or non-target control and resorted based on GFP expression at day 5. b. Representative example of staining on resorted Tregs stimulated with PMA and ionomicin for 4 hours at day 5 (n=4).",
    "ncbi_link": "AKT1: 207
AKT2: 208
AKT3: 10000"
  },
  {
    "caption": "Sorted Tregs were stimulated with anti-CD3, anti-CD28, IL-2 and shRNA specific for AKT1, AKT2, AKT3, or non-target control and resorted based on GFP expression at day 5. c. Statistical analysis of the frequency of IFN+Foxp3+ Tregs after AKT silencing (n=4).",
    "ncbi_link": "AKT1: 207
AKT2: 208
AKT3: 10000"
  },
  {
    "caption": "Sorted Tregs were stimulated with anti-CD3, anti-CD28, IL-2 and shRNA specific for AKT1, AKT2, AKT3, or non-target control and resorted based on GFP expression at day 5. d. shRNA transduced cells were co-cultured with CFSE-labeled Tresp and Tresp proliferation was measured after 4 days. e. Statistical analysis of the percentage of suppression by AKT1-, AKT2- and AKT3-silenced Tregs as compared to NT-transduced cells of n=6 experiments performed. *p < 0.05, **p < 0.005, ***p < 0.0005.",
    "ncbi_link": "AKT1: 207
AKT2: 208
AKT3: 10000"
  },
  {
    "caption": "a. Sorted CD4+CD25hiCD127- Tregs were stimulated in the presence of vehicle (white squares) and IL-12 either alone (white circles) or in the presence of LY294002 or MK2206 (black circles) for 3 days and IFNG and TBX21 gene expression was examined every 24 hours. Statistical analysis of n=8 independent experiments performed.",
    "ncbi_link": "IFNG: 3458
TBX21: 30009"
  },
  {
    "caption": "C: Representative images from fluorescence live cell microscopy of Dad1-GFP strains with Duo1WT-6xFlag or  Duo1∆SxIP-6xFlag. Displayed cells are in either metaphase (left) or anaphase (right). Scale bar: 2 μm. D: Quantification of signal intensities of Dad1-GFP at metaphase and anaphase kinetochore clusters of Duo1WT-6xFlag  and Duo1∆SxIP-6xFlag strains. Bars represent the mean +/- standard deviation. Each spot represents the value measured for a single  kinetochore cluster. Values were normalized to the mean value of  metaphase clusters of the Duo1WT-6xFlag strain. A one-way ANOVA test with Sidak's multiple comparisons test was used to calculate p values. n ≥ 76 kinetochore clusters.",
    "ncbi_link": "Flag: 
Duo1: 852819"
  },
  {
    "caption": "F: Analysis of  cell cycle progression  of yeast  strains with different  Duo1 alleles. Accumulation and degradation of Pds1 after release from α factor  arrest was analyzed by western blot (left). An antibody against Pgk1 was used to confirm equal protein amounts in samples. The DNA content of the cell population at indicated  time points after release from  α factor arrest was analyzed by  FACS  (right). Cells in G1 phase and mitosis are characterized by a 1C and 2C   DNA content, respectively. An intermediate DNA content is detected for cells in S phase.",
    "ncbi_link": "Duo1: 852819"
  },
  {
    "caption": "B: Representative images from live cell microscopy of Dam1WT and dam1-19 strains with Dad1-GFP. Displayed cells are in  metaphase (left) or anaphase (right). Scale bar: 2 μm. C: Quantification of Dad1-GFP signal intensities at metaphase and anaphase kinetochore  clusters of  Dam1WT and dam1-19 strains. Bars represent the mean +/- standard deviation. Each spot represents the value measured for a single  kinetochore  cluster. Values were normalized to the mean value of metaphase clusters of the  Dam1WT strain. p-values were obtained by a one-way ANOVA test with Sidak's multiple comparisons test. n ≥ 86 kinetochore clusters.",
    "ncbi_link": "Dam1: 853010
dam1: 853010"
  },
  {
    "caption": "E, F: GST-Bim1185-344 pull down assays. Binding of immobilized GST-Bim1185-344 to Duo1-6xFlag was analyzed in context of (E) selective inhibition of Mps1  (mps1-737) or overexpression of Mps1 from a galactose-inducible promotor (F). For inhibition of Mps1, cells were grown at the restrictive  temperature of 37 °C. Overexpression of Mps1 was achieved by growing cells in medium containing  galactose. GST-Bim1185-344 immobilized on  glutathione sepharose beads were incubated with soluble cells lysates of the respective strains grown under the mentioned conditions. Binding of Duo1 was analyzed by  western blot. Pgk1  indicates equal protein amounts in all samples.",
    "ncbi_link": "Mps1: 851533"
  },
  {
    "caption": "G: Live cell microscopy of a Dad1-GFP strain under conditions of Mps1 overexpression. The localization of Dam1c was visualized by  Dad1-GFP in either an Mps1WT or Mps1 overexpression setup (pGal-Mps1). Ndc80-mRuby2 was used as reference point for the localization of kinetochores. Images show representative metaphase cells from both strains. The area in the white dashed box is shown as magnification in the lower left corner. White arrowheads point at nuclear microtubules  decorated by Dad1-GFP. Please note that brightness and contrast of the  Dad1-GFP image in the lower row were optimized to make the nuclear microtubules  clearly visible. Scale bar: 2 μm.",
    "ncbi_link": "Gal: 855828
Mps1: 851533"
  },
  {
    "caption": "D: Serial dilution assay  of yeast strains with different  Duo1 and Ndc80 alleles in an Ndc80-FRB-GFP background. Ndc80WT or Ndc80∆490-510 integration constructs were integrated at the LEU2 locus and combined with either the Duo1WT or Duo1∆SxIP allele (at DUO1 locus). Cells were spotted on  YEPD medium without and with 1 µg/ml Rapamycin and incubated at the indicated temperatures.",
    "ncbi_link": "GFP: 
Duo1: 852819
DUO1: 852819
LEU2: 850342
Ndc80: 854662"
  },
  {
    "caption": "B:  Serial dilution assay  of  yeast  strains with 6xFlag-tagged  Duo1WT or Duo1∆SxIP and Ask1WT, Ask12A or Ask12D. Cells were grown at the indicated temperatures and images were taken two days (25 °C, 30 °C and 37 °C) or four days (16 °C) after spotting.",
    "ncbi_link": "Flag: 
Ask1: 853814
Duo1: 852819"
  },
  {
    "caption": "A. Assessment of protein levels in different AIFM1 knockout clones. Lysates from different AIFM1 knockout clones and wild type cells were analyzed by reducing SDS-PAGE and immunoblotting. MIA40/CHCHD4 levels are not changed in AIFM1 knockout HEK293 cells.",
    "ncbi_link": "AIFM1: 9131"
  },
  {
    "caption": "D. Assessment of protein levels in HEK293 cells, AIFM1 knockout cells and AIFM1 knockout cells with reintroduced AIFM1-HA (expression of AIFM1-HA induced for one day). Different amounts of lysates from the indicated cells were analyzed by reducing SDS-PAGE and immunoblotting. While levels of MIA40 were largely unchanged, levels of many MIA40/CHCHD4 substrates were diminished in AIFM1 knockout cells. N = 3 biological replicates.",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "F. BN-PAGE analyses of HEK293 cells, AIFM1 knockout cells and AIFM1 knockout cells with reintroduced AIFM1-HA or AIFM1. Complex I was resolved from isolated mitochondria with blue native electrophoresis (BN-PAGE) followed by immunoblotting or in gel determination of the complex I specific activity. Levels of complex I were decreased in AIFM1 knockout cells. N = 3 biological replicates",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "A. In organello import assay with NDUFS5, NDUFB7 and as control the matrix protein SOD2. In vitro translated radioactive proteins were incubated with mitochondria isolated from HEK293 and AIFM1 knockout cells. Non-imported proteins were removed by treatment with Proteinase K. Imported proteins were analyzed by reducing SDS-PAGE and autoradiography. Signals were quantified using ImageQuantTL and the amount of imported protein was plotted. NDUFS5 import is strongly affected by loss of AIFM1. Import of NDUFB7 is less affected and SOD2 import remained unaffected. This is despite the fact that the core domains important for oxidative folding of NDUFS5 an NDUFB7 are very similar.",
    "ncbi_link": "AIFM1: 9131"
  },
  {
    "caption": "B. Oxidation kinetics of endogenous NDUFB7 and NDUFS5. HEK293 cells, AIFM1 knockout cells and AIFM1 knockout cells complemented with AIFM1-HA were analyzed by pulse-chase experiments coupled to redox state determination. To this end, cells were incubated with 35S-Met for 5 min (pulse). After removal of 35S-Met, cells were left in \"cold\" Met for different chase times. Further oxidation was stopped by addition of trichloroacetic acid (TCA). Free thiols but not thiols in disulfide bonds were modified using mmPEG24 and then MIA40/CHCHD4 substrates were enriched by immunoprecipitation (IP), and analyzed by non-reducing SDS-PAGE and autoradiography. Occurrence of oxidized NDUFB7 was slightly delayed in AIFM1 knockout cells. NDUFS5 levels dropped rapidly and only little oxidized NDUFS5 could be observed. N = 4 biological replicates for NDUFB7 and NDUFS5.",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "C. Synthesis of NDUFS5 and NDUFB7 in wild type and AIFM1 knockout cells. Cells were incubated with 35S-Met for 5 min (pulse), and then MIA40/CHCHD4 substrates were enriched by immunoprecipitation (IP), and analyzed by non-reducing SDS-PAGE and autoradiography. NDUFS5 and NDUFB7 are synthesized in equal amounts in wildtype and AIFM1 knockout cells.",
    "ncbi_link": "AIFM1: 9131"
  },
  {
    "caption": "D. Interaction between endogenous MIA40/CHCHD4 and its substrates in wild type and AIFM1 knockout cells. Cells were subjected to native immunoprecipitation (IP) against endogenous MIA40/CHCHD4. Precipitates were analyzed by SDS-PAGE and immunoblotting against the indicated proteins. In AIFM1 knockout cell interaction between MIA40/CHCHD4 and its substrates is strongly affected with the interaction between MIA40/CHCHD4 and NDUFS5 almost completely abolished. This is despite the fact that NDUFS5 and NDUFB7 are synthesized in equal amounts in wildtype and AIFM1 knockout cells, indicating that lowered steady state levels of these proteins are consequence of a lacking interaction with MIA40/CHCHD4 rather than the cause. Quantification using Image lab. Data from 2 experiments were combined and standard deviations are presented. Asterisk indicates background band orange arrow indicates signal of NDUFS5 and NDUFB7 in AIFM1 KO cells, respectively.",
    "ncbi_link": "AIFM1: 9131"
  },
  {
    "caption": "A. Assessment of MIA40/CHCHD4 variant-AIFM1 interaction. The indicated MIA40/CHCHD4-Strep variants were affinity precipitated (AP) under native conditions after stopping thiol-disulfide exchange reactions by NEM incubation. Precipitates were tested for AIFM1, ALR and MIA40/CHCHD4 by reducing SDS-PAGE and immunoblotting. 1% of the total lysate was loaded as input control. M, mock control not expressing MIA40-Strep. Both, wildtype MIA40/CHCHD4 and MTS-MIA40/CHCHD4 but not MIA40/CHCHD4∆1-40 variants coprecipitated AIFM1. All mitochondria-localized variants precipitate ALR indicating redox functionality. Arrowhead indicates endogenous MIA40/CHCHD4.",
    "ncbi_link": "AIFM1: 9131
MIA40: 131474"
  },
  {
    "caption": "C. Emetine-chase experiments to assess the stability of the AIFM1/CHCHD4 complex. AIFM1 knockout cells stably expressing AIFM1-HA (C) were treated for the indicated times with the ribosome inhibitor emetine. Then, cells were lysed under native conditions (triton X-100), and AIFM1-HA (C) were precipitated. Precipitates were analysed by reducing SDS-PAGE and immunoblotting. MIA40/CHCHD4 and AIFM1 interact over a period of at least 6-8 hours AP, affinity precipitation; asterisk, background band.",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "A. Gel filtration analysis to assess the AIFM1-MIA40 complex in HEK293 cells. HEK293 cells, cells lacking AIFM1 (AIFM1 knockout, AIFM1 KO) or AIFM1 knockout cells complemented with AIFM1-HA were lysed under native conditions (triton X-100), and the cleared lysates subjected to gel filtration analysis. Eluted fractions were subjected to TCA precipitation, resuspension in loading buffer containing SDS and DTT, and subsequent immunoblotting against AIFM1 and MIA40. Endogenous AIFM1 and all endogenous MIA40 migrate in a complex with a size larger than 150 kDa (as judged by comparison to protein markers: apoferritin 443 kDa; β-amylase 200 kDa; alcohol dehydrogenase 150 kDa; bovine serum albumin 66 kDa; carbonic anhydrase 29 kDa). Absence of AIFM1 results in migration of MIA40 at the height of monomeric MIA40. This behavior is partially rescued by complementation with AIFM1-HA. B. Gel filtration analysis of a MIA40 variant lacking the first 40 amino acids (∆1-40 MIA40/CHCHD4-Strep), which constitute the AIFM1 interaction motif. Experiment was performed as described in (A). AIFM1 and endogenous MIA40/CHCHD4 migrate in a complex with a size larger than 150 kDa, while N-terminally truncated MIA40/CHCHD4 migrates as monomer. For number of biological replicates and quantifications, see 5C. C. Quantification of 5A,B and Appendix Figure S9. Quantification of the areas representing the region of monomeric MIA40/CHCHD4 and the AIFM1-MIA40/CHCHD4 complex, respectively was performed. Quantifications consistently show that AIFM1 knockout, siRNA-mediated depletion of AIFM1 and overexpression of MIA40/CHCHD4 all resulted in an increase of monomeric MIA40/CHCHD4 indicating that the amounts of available AIFM1 with respect to the amounts of MIA40/CHCHD4 are tightly regulated. The numbers below the bars indicate the numbers of biological replicates performed. Averages and standard deviations are presented.",
    "ncbi_link": "HA: 
AIFM1: 9131
CHCHD4: 131474
MIA40: 131474"
  },
  {
    "caption": "F. Assessing the solubility of MIA40/CHCHD4 in the IMS. Mitochondria were isolated form the indicated cell lines and the outer membrane destroyed by hypoxic swelling. MIA40/CHCHD4 remains bound to these mitoplasts when they were isolated from wildtype cells or AIFM1 knockout cells that had been complemented with AIFM1-HA. It was released from cells lacking AIFM1. This indicates that MIA40/CHCHD4 in wildtype cells is membrane-associated via AIFM1.",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "A. Oxidation kinetics of NDUFB7 and NDUFS5 in the presence of the proteasome inhibitor MG132. HEK293 cells, AIFM1 knockout cells and AIFM1 knockout cells complemented with AIFM1-HA were analysed by pulse-chase experiments coupled to redox state determination. Levels and occurrence of oxidized NDUFB7 was not changed in the presence of MG132. Conversely, NDUFS5 levels were strongly increased. In AIFM1 knockout cells, large amounts of NDUFS5 accumulated in their reduced state indicating impaired oxidation-dependent protein import. The fraction of oxidized protein accumulating is slightly larger than in the absence of MG132. N = 1 biological replicate for NDUFB7 and 2 biological replicates for NDUFS5.",
    "ncbi_link": "HA: 
AIFM1: 9131"
  },
  {
    "caption": "B) Mean fold-changes for each of the 33 proteins that were LRRK2-dependently regulated in both cohorts using a pairwise t-test comparing the four subgroups (HC, NMC, iPD and LRRK2 PD).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "A) Pearson correlation scores and associated p-values [-log10] of all protein intensities with the MoCA total score. Either all PD patients (left), iPD patients (middle) or LRRK2 PD patients (right) were included in the analysis. Significantly correlated proteins with an FDR of 5% after Benjamini-Hochberg correction are highlighted in red.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "B) Pearson correlation scores and associated p-values [-log10] of all protein intensities with the UPDRS-III score. Either all PD patients (left), iPD patients (middle) or LRRK2 PD patients (right) were included. Significantly correlated proteins with an FDR of 5% after Benjamini-Hochberg correction are highlighted in red.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(D, E) The relative levels of endogenous Zwf1 protein with a GFP tag were analyzed by immunoblots in WT, snf1Δ or snf1Δmig1Δ cells (D). Protein extracts were probed with an anti-GFP antibody. Mcm2 was applied as a loading control. Three independent experiments were carried out and the relative fold changes were measured by Image J (E). Error bars represent standard deviations (SD) from three biological repeats. Statistical significance was evaluated based on Student's t-test (*0.01< P-values <0.05; **0.001< P-values <0.01).",
    "ncbi_link": "mig1: 852848
snf1: 852088"
  },
  {
    "caption": "(C) Rad53 phosphorylation in various snf1 alleles in response to HU. The plasmids expressing the indicated snf1 alleles were transformed into snf1Δ. Rad53 phosphorylation was detected as above.",
    "ncbi_link": "snf1: 852088"
  },
  {
    "caption": "(D) The snf1 kinase-defective mutants are sensitive to HU. Yeast spot assays were performed as in Fig 2A. The phospho-mimetic snf1T210D (a constitutive active mutant) was applied as a control for nonphosphrylable snf1T210A.",
    "ncbi_link": "snf1: 852088"
  },
  {
    "caption": "mig1Δ restores Rad53 phosphorylation of the snf1 mutants in the presence of HU. The experiments were done as in Fig 2.",
    "ncbi_link": "mig1: 852848
snf1: 852088"
  },
  {
    "caption": "(E, F) snf1Δ shows less RPA on chromatin, which can be restored by mig1Δ. Cells were collected and fractionated into chromatin-bound (Chromatin) and non-chromatin-bound fractions (non-Chromatin) followed by immunoblotting. Tubulin and Orc2 were applied as controls for non-chromatin and chromatin fractions, respectively. The signals were quantified by Image J and quantifications were shown in (F). Error bars represent SD from three biological repeats. Statistical significance was evaluated based on Student's t-test (*0.01 < P-values < 0.05).",
    "ncbi_link": "mig1: 852848
snf1: 852088"
  },
  {
    "caption": "Phospho-mimetic mig1-2D bypasses the role of SNF1 in HU resistance (C)",
    "ncbi_link": "mig1: 852848
SNF1: 852088"
  },
  {
    "caption": "Phospho-mimetic mig1-2D bypasses the role of SNF1 in RPA recruitment (D). (E) The diagram of the strategy to reinforce the Mig1-Ssn6 interaction via a GFP and GBP pair (left panel). The persistent Mig1-Ssn6 association abolishes the phospho-mimicking effect of mig1-2D (right panel).",
    "ncbi_link": "mig1: 852848
SNF1: 852088"
  },
  {
    "caption": "(D) Phosphorylation of Mig1 T489 S495 completely restores the ZWF1 mRNA levels in snf1Δ. The experiments were done as in Fig 1. Error bars represent SD from three biological repeats. Statistical significance was evaluated based on Student's t-test (*0.01 < P-values < 0.05; **0.001 < P-values < 0.01).",
    "ncbi_link": "Mig1: 852848
snf1: 852088
ZWF1: 855480"
  },
  {
    "caption": "(B) The effects of α-KG on the HU sensitivity of snf1Δ and other checkpoint mutants. Yeast spot assays were performed as in Fig 2A.",
    "ncbi_link": "snf1: 852088"
  },
  {
    "caption": "(D) α-KG restores Rad53 phosphorylation in snf1Δ. CBB indicates coomassie bright blue (CBB) staining of the membrane as the loading control.",
    "ncbi_link": "snf1: 852088"
  },
  {
    "caption": "(E) The effects of α-KG on the HU sensitivity of Rfa1 zinc finger mutants (C486S, C491S, C505S, C508S). Yeast spot assays were performed as in Fig 2A.",
    "ncbi_link": "Rfa1: 851266"
  },
  {
    "caption": "c) Morphological analysis. Jurkat T cells were treated with the indicated drugs or transduced with lentivirus ATG5, ATG5-K130R, Beclin 1 or control constructs for 48 h. Enlarged and multinucleated cells were seen as a consequence of ATG5 or ATG5-K130R lentiviral gene transfer or of etoposide treatment. Increased Beclin 1 levels or rapamycin treatment had no such effect. Representative examples of morphology are shown. Scale bar, 10 μm. Right: statistical analysis of the data. At least 100 cells were counted for each condition. Values are means±s.d. (n=3).",
    "ncbi_link": "ATG5: 9474
Beclin 1: 8678"
  },
  {
    "caption": "(d) Immunoblotting. Enforced expression of ATG5, Beclin 1, or ATG5-K130R following lentiviral gene transfer.",
    "ncbi_link": "ATG5: 9474
Beclin 1: 8678"
  },
  {
    "caption": "(e) Time-lapse microscopy. HeLa H2B-mCherry-α-tubulin-EGFP cells were transduced by lentiviral gene transfer as indicated. Only ATG5-overexpressing cells demonstrated evidence for mitotic catastrophe (see also Supplementary Movies). As with the GFP control, the Beclin 1 construct also included GFP, hence the intensity in green was very high. Scale bar, 10 μm.",
    "ncbi_link": "ATG5: 9474
Beclin 1: 8678"
  },
  {
    "caption": "(a) Cell cycle analysis. After lentivirus gene transfer, Jurkat T cells overexpressing ATG5 or GFP were followed for the indicated times and analysed for DNA content by flow cytometry. Untransduced cells were left untreated or treated with etoposide for comparison. Values are means±s.d. (n=3). Right: representative flow cytometry diagrams for the 48 h time point.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(b) Cell cycle analysis. Jurkat cells were cultured as indicated for 48 h. Only under conditions of ATG5 induction, we observed an accumulation of cells in G2- or M-phase arrest. Results are representative of three independent experiments.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(c) Immunoblotting. Jurkat T cells overexpressing ATG5 or GFP were cultured for the indicated times after transduction and analysed. As controls, cells were treated with etoposide or rapamycin. Although rapamycin, similar to etoposide, induced autophagy, no increase in ATG5 expression and no cell cycle arrest were observed. ATG5 overexpression and etoposide treatment resulted in a similar expression pattern for all proteins investigated. Each immunoblot is representative of at least three independent experiments.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(a) Flow cytometry. Untreated Jurkat T cells, cells treated with etoposide continuously (0.25 μM), or transduced with lentivirus ATG5 or GFP were cultured for 48 h, fixed, permeabilized and exposed to antiphospho-H2AX (Ser139) antibody, then stained with antimouse-APC-conjugated antibody, and analysed using a flow cytometer.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(b) Confocal microscopy. Untreated HeLa cells, cells treated with etoposide continuously (0.25 μM), or transduced with lentivirus ATG5 were cultured for 48 h. Additional DAPI nuclear staining was used. Scale bar, 10 μm. Right: phospho-H2AX was quantified by measuring the mean fluorescence intensity (MFI) in five high-power fields of each condition using IMARIS software. Values are means±s.d.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(a) Immunoblotting. Jurkat T cells overexpressing ATG5 or control cells were cultured in the presence and absence of 3-MA for 48 h. 3-MA blocked the formation of LC3-II and p62 degradation, indicating that it indeed inhibited ATG5-induced autophagy. Results are representative of three independent experiments.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(b) Cell cycle analysis. Normal Jurkat T cells and cells overexpressing ATG5 were cultured for 48 h in the presence and absence of 3-MA. Induction of G2- or M-phase arrest was seen as a consequence of ATG5 overexpression independent of treatment with 3-MA, as normal Jurkat T cells exhibited no G2/M arrest following 3-MA treatment. Representative flow cytometry diagrams are shown (n=3). Moreover, induction of autophagy by Beclin 1 overexpression or starvation failed to produce cell cycle arrest (Supplementary Fig. S4).",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(c) Morphological analysis. Normal Jurkat T cells and cells overexpressing ATG5 were cultured for 48 h in the presence and absence of 3-MA and analysed. Representative examples of morphology are shown (n=3); large multinucleated cells and cells with abnormal nuclei were seen as a consequence of ATG5 overexpression independent of 3-MA. Neither induction of autophagy by Beclin 1 overexpression nor starvation resulted in such abnormal cells (Supplementary Fig. S4). Scale bar, 10 μm. (",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(d) Viability assays. Jurkat T cells either overexpressing ATG5 following lentiviral gene transfer or treated with etoposide were cultured in the presence and absence of the indicated pharmacological inhibitors for the indicated times to block autophagy and caspase activity. All values are means±s.d. (n=3).",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(c) Subcellular fractionation and immunoblotting of the nuclear fraction. Jurkat T cells, either treated with etoposide, or overexpressing ATG5 following lentiviral gene transfer, were cultured in the presence and absence of leptomycin B for 72 h. Leptomycin B increased relative ATG5 and Beclin 1 levels in the nucleus.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(d) Subcellular fractionation and immunoblotting. Jurkat T cells were transduced to express ATG5-ΔNES, ATG5, or GFP. Although increased levels of ATG5 were observed in both cytoplasm and nucleus, ATG5-ΔNES accumulated following lentiviral gene transfer in the cytoplasm only. Full-length immunoblots are provided in Supplementary Fig. S11.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(e) Immunoblotting. ATG5-ΔNES overexpression induced LC3-II formation and p62 degradation, indicating increased autophagic flux.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(f) Cell cycle analysis. Jurkat T cells overexpressing ATG5 or ATG5-ΔNES, as well as control cells were cultured for 48 h. Induction of G2 and M phase arrest was seen as a consequence of ATG5, but not ATG5-ΔNES overexpression. As an additional control, we transduced cells with GFP, which, similar to ATG5-ΔNES-overexpressing cells, failed to exhibit G2- and M-phase arrest. Representative flow cytometry diagrams are shown (n=3).",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(g) Morphological analysis. Non-transduced Jurkat T cells and cells overexpressing ATG5 or ATG5-ΔNES were cultured for 48 h. Large, multinucleated cells were seen as a consequence of ATG5, but not ATG5-ΔNES overexpression. Representative examples are shown (n=3). Scale bar, 10 μm.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(a) Lysates of Jurkat T cells overexpressing ATG5 or treated with etoposide (48-h cultures) were immunoprecipitated with anti-ATG5 or antisurvivin antibodies. A physical interaction between ATG5 and survivin, absent in untreated or GFP-expressing control cells, was detected reciprocally. Full-length immunoblots are provided in Supplementary Fig. S12.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(b) Jurkat T cells overexpressing ATG5-ΔNES exhibited no ATG5/survivin molecular interaction. (c) The ATG5-K130R mutant did show coprecipitation of survivin with ATG5.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(d) Calpain-mediated, truncated ATG5 (tATG5), that is, the N-terminal part of ATG5, failed to bind survivin. The ATG5-K130R mutant was the control.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(e) Confocal microscopy. MDA-MA-231 cells were etoposide treated or transduced as indicated (48-h cultures) and stained. In untreated cells, survivin and ATG5 were in the cytosol with no colocalization. ATG5-transduced cells exhibited ATG5/survivin colocalization in the nucleus. ATG5-ΔNES-transduced cells showed survivin, but not ATG5, in the nuclei of cycling cells. Numerical analysis was performed and Pearson's correlation coefficients are indicated in the images. Scale bar, 10 μm. Right: Statistical analysis (analysis of variance) is presented in which the results of ten representative cells within each group were integrated. Values are means±s.d.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(g) Confocal microscopy. HeLa cells treated with etoposide or transduced as indicated (48-h cultures) were stained with centromere-specific antiserum and anti-Aurora B (top panels) or antisurvivin antibodies (lower panels). In untreated or ATG5-ΔNES transduced cells, both Aurora B and survivin were recruited to prometaphase centromeres and located at the central spindle during anaphase where they no longer colocalized with centromeres. In contrast, etoposide-treated or ATG5-transduced cells recruited much less Aurora B to prometaphase centromeres. Such recruitment, however, was observed during anaphase. Compared with cells in normal mitosis, survivin, although reduced, was recruited to centromeres in prometaphase, but, similar to Aurora B, remained attached to centromeres during anaphase. Such mislocation of Aurora B and survivin was associated with severe chromosome alignment and segregation defects. Colocalization images were prepared using Imaris software. Numerical analysis was performed and correlation coefficients are indicated. Scale bar, 2 μm.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "A, B. Western blot showing the absence of HUWE1 protein in 293T (A) and HeLa (B) cells subjected to CRISPR/Cas9-mediated HUWE1-deletion.",
    "ncbi_link": "Cas9: 
CRISPR: 
HUWE1: 10075"
  },
  {
    "caption": "C, D. HUWE1-knockout 293T (C) and HeLa (D) cells show increased DNA breaks in the absence of exogenous DNA damage treatment. Results from the Alkaline Comet Assay are shown. The \"n\" numbers of comet tails analyzed (pooled from two independent experiments), as well as the mean, are indicated on the graphs. HUWE1-knockout HeLa cells did not show increases breakage in the Neutral Comet assay (Fig EV1B), indicating that the majority of breaks observed in cycling HUWE1-knockout cells are not double strand breaks, but rather single strand breaks and other types of lesions.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "E, F. Increased S-phase arrest in HUWE1-knockout 293T (E) and HeLa (F) cells. Cycling cells were incubated with BrdU and subjected to BrdU/PI bi-dimensional flow cytometry. Representative flow cytometry profiles are presented in Fig EV1D-F. Bars represent the fold increase in the percentage of cells with S-phase DNA content (between 2N and 4N) but negative for BrdU staining. Bars represent the average of three independent experiments, with error bars showing SD. The p-values are 0.0091 (E) and 0.0007 (F).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "G, H. The DNA fiber assay shows reduced replication tract length in HUWE1-knockout 293T (G) and HeLa (H) cells in the absence of exogenous DNA damage treatment. The \"n\" numbers of fibers analyzed (pooled from three independent experiments), as well as the mean +/- SEM, are indicated on the graphs. P-values are 9.8x10-22 (G) and 1.0x10-10 (H).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "A. HUWE1 levels are efficiently downregulated by two different HUWE1 siRNA oligonucleotides in 8988T cells. B. Quantification of HUWE1 expression following siRNA treatment. Band intensity was quantified using ImageJ software and normalized to Tubulin loading control. The average of three experiments is shown. Error bars indicate SD.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "C-E. Cell cycle analyses by flow cytometry using BrdU/PI double staining show increased replication arrest in HUWE1-depleted 8988T cells in the absence of exogenous DNA damage treatment. C. Representative flow cytometry profiles of control and HUWE1-knockdown cells. R1-labeled region indicates mid and late S-phase cells (BrdU-positive, >2N DNA content), while R2-labeled region indicates S-phase arrested cells (BrdU-negative, DNA content between 2N and 4N).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "C-E. Cell cycle analyses by flow cytometry using BrdU/PI double staining show increased replication arrest in HUWE1-depleted 8988T cells in the absence of exogenous DNA damage treatment. C. Representative flow cytometry profiles of control and HUWE1-knockdown cells. R1-labeled region indicates mid and late S-phase cells (BrdU-positive, >2N DNA content), while R2-labeled region indicates S-phase arrested cells (BrdU-negative, DNA content between 2N and 4N). D. Quantification of S-phase cells. Percentage of cells in R1 region is shown. Bars represent the average of three independent experiments. Error bars indicate SD. P-value is 0.0014. E. Quantification of S-phase arrested cells. Bars represent the fold increase in the percentage of cells in R2 region, normalized to siControl-treated cells. The average of three independent experiments is shown. Error bars indicate SD. P-value is 0.0135.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "F. DNA fiber experiment showing reduced replication tract length in HUWE1-depleted HeLa cells in the absence of exogenous DNA damage treatment. The \"n\" numbers of fibers analyzed (pooled from two independent experiments), as well as the mean, are indicated on the graphs.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "G, H. Clonogenic assay showing that HUWE1 knockdown in 8988T cells are sensitive to UV (G), and HU (H). As controls, both cells transfected with non-targeting siRNA (siControl), and non- transfected cells, were used. Note that the siHUWE1#2 oligonucleotide shows a stronger downregulation of HUWE1, and confers increased sensitivity compared to siHUWE1#1. The average of nine experiments is shown. Error bars represent SEM. P-values (representing the statistical difference between the samples at the highest dose treatment) are: 4.55x10-9 (G) and 1.8x10-8 (H).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "I. DNA fiber experiments showing decreased replication tract length following UV-B treatment (30J/m2) in HUWE1-depleted HeLa cells. The \"n\" numbers of fibers analyzed (pooled from three independent experiments), as well as the mean +/- SEM, are indicated on the graphs. P-value is 2.11x10-20.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "A. iPOND experiment showing that HUWE1 localizes to replication forks in 293T cells. Binding to nascent DNA was increased after UV exposure. Because of the difficulties in removing all the crosslinks in high molecular weightproteins, HUWE1 is detected as a high molecular weight smear. A control experiment using the HUWE1-knockout cells (shown in the right side panel) confirmed the specificity of the HUWE1 signal.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "D. As control, endogenous HUWE1 was depleted by siRNA treatment, and extracts were subjected to anti-HUWE1 immunoprecipitation. The HUWE1 blot shows that much less HUWE1 is precipitated by anti-HUWE1 antibodies from HUWE1-knockdown cells than control, as expected. PCNA is co-precipitated by anti-HUWE1 antibodies from control, but not HUWE1-depleted cells, showing that the interaction is specific and not due to unspecific binding of PCNA to anti-HUWE1 antibodies",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "G. Co-immunoprecipitation experiment from control and RAD18-knockout 293T cells, showing that the HUWE1-PCNA interaction is not affected by loss of PCNA ubiquitination. RAD18-knockout cells were obtained by CRISPR/Cas9 technology. The RAD18 and PCNA blots show loss of RAD18, and of PCNA ubiquitination respectively.",
    "ncbi_link": "Cas9: 
CRISPR: 
RAD18: 56852"
  },
  {
    "caption": "J. GST-pulldowns using GST-PCNA or GST-empty as control, and extracts of 293T cells transfected with Myc-HUWE1C-ter, showing interaction of this fragment with recombinant PCNA.",
    "ncbi_link": "PCNA: 5111"
  },
  {
    "caption": "A, B. GST-pulldowns showing that HUWE1 PIP-box mutants do not interact with PCNA. A. Recombinant GST-tagged HUWE1C-ter, either wild-type or PIP-box mutant variants (QVFF and VFF -the indicated residues, critical for the PIP-box, were mutated to A), were purified from bacteria (see Coomassiestaining) and employed for GST-pulldowns using extracts of 293T cells. PCNA co-precipitated with wild-type, but not PIP-box mutants. B. Reciprocal GST-pulldown using recombinant GST-PCNA and extracts of 293T cells overexpressing Myc-HUWE1C-ter. Wild-type, but not the PIP-box mutant (VFF) HUWE1 fragment bound to GST-PCNA.",
    "ncbi_link": "HUWE1: 10075
PCNA: 5111"
  },
  {
    "caption": "C, D. Reciprocal co-immunoprecipitationexperiments showing that PIP-box mutation abolishes PCNA interaction. C. 293T cells were transfected with Myc-HUWE1C-ter variants, and subjected to anti-PCNA (C) or anti-Myc (D) immunoprecipitation. Only wild-type, but not PIP-box mutant (VFF) HUWE1 interacted with PCNA in both experimental setups.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "E. Mutation of the PIP-box in full-length HUWE1 also blocks PCNA interaction. Full-length Myc-tagged HUWE1 (wild-type or PIP-mutant) was transfected in 293T cells. Following Myc-immunoprecipitation, endogenous PCNA was detected in wild-type, but not PIP-box mutant (FF) complexes.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "A. Stable expression of Myc-tagged wild-type, PIP-box mutant, and catalytic inactive HUWE1 variants in HUWE1-knockout 293T cells. The Western blot shows that expression of the Myc-tagged variants stably transfected in the knockout cell lines, is similar to the endogenous HUWE1 expression.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "B. Myc-tag immunoprecipitation using extracts of the corrected cell lines described above. As expected, PCNA co-precipitates with wild-type, but not PIP-box mutant HUWE1 (FF).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "C. iPOND experiment using HUWE1-knockout 293T cells, corrected with wild-type or PIP-mutant HUWE1. The PIP-mutant shows reduced crosslinking to nascent DNA, indicated defective recruitment to replication forks.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "D. Clonogenic assay showing that stable expression of wild-type HUWE1, but not of the PIP box mutant or the catalytic mutant, corrects the HU sensitivity of the HUWE1-knockout 293T cells. Shown is the average of 3 independent experiments -/+SD. If not indicated otherwise, the p-values shown specify the statistical significance relative to 293T (for the 0.5mM HU condition). P-values are: 0.0003 (293T vs HUWE1-/-; 0.157 (293T vs HUWE1-/- +WT); 0.0045 (293T vs HUWE1-/- +FF); 0.0006 (293T vs HUWE1-/- +C4341A; 0.047 (HUWE1-/- +WT vs HUWE1-/- +FF).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "E. The S-phase arrest phenotype is also rescued by wild-type, but not PIP-mutant or catalytic mutant HUWE1. S-phase arrested cells were quantified using the BrdU/PI bi-dimensional flow cytometry assay. Shown is the average of 3 independent experiments -/+SD. The p-values shown specify the statistical significance relative to 293T (0.018, 0.957, 0.015, and 0.024 respectively). A quantification of the same data, showing the percentage of cells arrested in S-phase, is shown in Fig EV3A.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "F. Normal replication tract length, quantified using the DNA fiber assay, is restored by expressing wild-type, but not PIP-mutant HUWE1, in the HUWE1-knockout 293T cells. The \"n\" numbers of fibers analyzed (pooled from three independent experiments), as well as the mean +/- SEM, are indicated on the graphs. If not indicated otherwise, the p-values shown specify the statistical significance relative to 293T. P-values are: 1.47x10-11 (293T vs HUWE-/- samples), 0.094 (293T vs HUWE-/- +WT samples), 1.40x10-7 (293T vs HUWE-/- +FF samples), 1.22x10-7 (HUWE-/- vs HUWE-/- +WT samples), 0.679 (HUWE-/- vs HUWE-/- +FF samples).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "G. Alkaline Comet Assay showing that wild-type, but not the FF mutant can correct the breakage phenotype of HUWE1-knockout 293T cells. The \"n\" numbers of comet tails analyzed (pooled from three independent experiments), as well as the mean +/- SEM, are indicated on the graphs. The p-values indicated are: 4.18x10-43 (293T vs HUWE-/- samples), 6.89x10-41 (HUWE1-/- +WT vs FF samples), and 5.97x10-50 (HUWE1-/- +WT vs C4341A samples).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "A, B. The impact of HUWE1 on H2AX phosphorylation and ubiquitination, under normal conditions (A) or upon induction of replication stress (2mM HU for 18h, or 2h after exposure to 40J/m2 UV). Control or HUWE1-knockout HeLa cells were analyzed.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "C. In vitro ubiquitination assay showing that recombinant HUWE1C-ter can mono-ubiquitinate H2AX.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "D. Wild-type, but not the PIP-mutant can correct the defective H2AX ubiquitination in HUWE1-knockout 293T cells.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": ". E. Chromatin immunoprecipitation showing that H2AX binding to the common fragile site FRA3B is reduced in HUWE1-knockout 8988T cells. Cells were treated with 600nM aphidicolin for 24h. Binding was quantified relative to input material. Shown is the average of 4 experiments -/+ SD. P-value is 4.4x10-6.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "F. Western blots showing that several H2AX ubiquitin ligases participate in H2AX ubiquitination following replication stress. HUWE1, RNF168, and BMI1 were knocked-down in HeLa cells. The efficiency of the knockdown is shown in Fig EV4. Cells were treated with 600nM aphidicolin for 24h, 2mM HU for 24h, or analyzed 2h after exposure to 40J/m2 UV.",
    "ncbi_link": "BMI1: 648
HUWE1: 10075
RNF168: 165918"
  },
  {
    "caption": "H. Chromatin fractionation experiments showing that HUWE1-knockout HeLa cells, treated with 2mM HU for 24h, fail to efficiently recruit BRCA1 and BRCA2 proteins to DNA. In contrast, 53BP1 chromatin association is not induced by HU treatment, and not affected by HUWE1 knockout, and thus can serve as loading control. Shown are blots of whole cell extract (WCE) samples, representing input material, and of chromatin pellet samples.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": " Whole cell lysates from HEK293T cells, with or without stable expression of ATF6α (as indicated) were immunoisolated with mouse anti-V5. RCN1 was transiently transfected into both cell lines in the experiment depicted in panel 3. Immunoisolated material was separated by SDS-PAGE under reducing conditions followed by western blotting to determine the co-isolation of ER proteins with ATF6α. Ig-HC (anti-BiP blot) indicates immunoglobulin heavy chains.",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " Whole cell lysates from HEK293T cells stably expressing ATF6α were either untreated (-) or treated (+) with 5 µM thapsigargin (TG) for 1 h. THBS4 was transiently transfected into cells in the experiment depicted in panel 2. ATF6α was either immunoisolated with anti-V5 (panel 1 and 3) or anti-HA (panel 2). For the experiment in panel 3 the cells were cross-linked prior to immunoisolation. Samples were separated by SDS-PAGE under reducing conditions followed by western blots to determine co-isolation of endogenous PDIR, ERp18 or exogenously expressed THBS4 with ATF6α. HC indicates immunoglobulin heavy chain. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": "HEK293T cells stably expressing ATF6α were either left untransfected (UT) or transfected with substrate-trapping mutants of PDI oxidoreductases. ATF6α was immunoisolated from cell lysates with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions and ATF6α detected by western blotting using rabbit anti-HA. Blots confirm mixed-disulfide complexes between ATF6α and ERp18, ERp57, and PDIR indicated with arrows (lanes 2, 4, 5). M, D and O refer to ATF6α monomer, dimer and oligomer respectively.",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " Whole cell lysates of HEK293T cells expressing an ATF6α mutant containing cysteine to alanine mutations in the lumenal domain (ATF6 DM) were transfected with PDI substrate-trapping mutants. ATF6α was immunoisolated with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions, and ATF6α detected with rabbit anti-HA. ",
    "ncbi_link": "ATF6: 22926
ATF6α: 22926"
  },
  {
    "caption": " HEK293T cells were co-transfected with ATF6α S1P and PDI substrate-trapping mutants and either left untreated (-) or treated (+) for 1 h with 5 µM TG to induce ER stress. ATF6α was immunoisolated from cell lysates with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions and ATF6α detected by western blotting using rabbit anti-HA. Blots indicate that mixed-disulfide complexes between ATF6α and PDI enzymes are regulated by ER stress. M, D and O refer to ATF6α monomer, dimer and oligomer respectively. *indicates positions of the ATF6α-PDI enzymes mixed-disulfide complexes. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " HEK293T cells were co-transfected with ATF6α S1P and PDI substrate-trapping mutants and either left untreated (-) or treated (+) for 1 h with 5 µg/ml tunicamycin to induce ER stress. ATF6α was immunoisolated from cell lysates with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions and ATF6α detected by western blotting using rabbit anti-HA. Blots indicate that mixed-disulfide complexes between ATF6α and PDI enzymes are regulated by ER stress. M, D and O refer to ATF6α monomer, dimer and oligomer respectively. *indicates positions of the ATF6α-PDI enzymes mixed-disulfide complexes. ** indicates hypoglycosylated ATF6α. Data shown are representative of three independent experiments. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " HEK293T cells were co-transfected with ATF6α S1P and PDI substrate-trapping mutants and either left untreated (-) or treated (+) for 1 h with 20 µM MG132 to induce ER stress. ATF6α was immunoisolated from cell lysates with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions and ATF6α detected by western blotting using rabbit anti-HA. Blots indicate that mixed-disulfide complexes between ATF6α and PDI enzymes are regulated by ER stress. M, D and O refer to ATF6α monomer, dimer and oligomer respectively. *indicates positions of the ATF6α-PDI enzymes mixed-disulfide complexes. ** indicates hypoglycosylated ATF6α. Data shown are representative of three independent experiments. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " HEK293T cells were co-transfected with ATF6α S1P and PDI substrate-trapping mutants and either left untreated (-) or treated (+) for 1 h with 5 µM TG to induce ER stress. Samples from (A) were rerun and probed with anti-sera raised against respective PDI enzymes as indicated (D). *indicates positions of the ATF6α-PDI enzymes mixed-disulfide complexes. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " HEK293T cells were co-transfected with the ERp18 substrate-trapping mutant and the indicated ATF6α constructs. Cell were allowed to recover for 24 h post-transfection before being either left untreated (-) or treated (+) for 1 h with 5 µM TG to induce ER stress. ATF6α was immunoisolated from cell lysates with mouse anti-ATF6α, separated by SDS-PAGE under non-reducing conditions and ATF6α detected by western blotting using rabbit anti-HA. The blot confirms that ATF6α C618A forms a stable complex with ERp18 trapping mutant following ER stress. M, D and O refer to ATF6 monomer, dimer and oligomer respectively. *indicates positions of the ATF6-ERp18 mixed-disulfide complexes. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " HEK293T cells were co-transfected with GFP-ATF6α and ERp18 trapping mutant constructs as indicated. GFP-ATF6α complexes were immunoisolated using GFP-trap. Immunoisolated material was separated by SDS-PAGE under non-reducing conditions and silver stained to detect ATF6α disulfide-linked complexes. MS analyses confirmed that protein bands indicated by black arrows are a complex comprising ATF6α and ERp18, whilst bands marked as monomer (M) and oligomer (O) contain ATF6α only. ",
    "ncbi_link": "GFP: 
ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": "CRISPR/Cas9-based knockout of ERp18 in HEK293T cells expressing ATF6α. ERp18 levels in control (WT) and knockout (KO) cells were detected with an antibody to ERp18.",
    "ncbi_link": "Cas9: 
CRISPR: 
ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " qPCR analysis of UPR target genes in the absence of ER stress. Wild type and ERp18 knockout HEK293T cells were untreated prior to isolation of mRNA for qPCR analysis. mRNA levels for Grp78, Grp94, ATF6α, ATF4, XBP1s (spliced form of XBP1) and ERp72 were normalized to GAPDH and then ERp18 KO levels compared to wild type. Error bars represent ± standard deviation for three independent experiments.   qPCR analysis of UPR target genes following ER stress. Wild type and ERp18 knockout HEK293T cells were treated with 1 µM TG for approximately 16 h prior to isolation of mRNA for qPCR analysis. mRNA levels for Grp78, Grp94, ATF6α, ATF4, XBP1s (spliced form of XBP1) and ERp72 were normalized to GAPDH and then ERp18 KO levels compared to wild type controls. Error bars represent ± standard deviation for three independent experiments.   ",
    "ncbi_link": "ATF4: 468
ATF6α: 22926
GAPDH: 2597
Grp94: 7184
Grp78: 3309
ERp72: 9601
ERp18: 51060
XBP1: 7494
XBP1s: 7494"
  },
  {
    "caption": " Levels of BiP protein in wild type or ERp18 KO cells before and after ER stress induction with thapsigargin (TG). Panel 1 compares wild type and ERp18 KO cells as indicated. Panel 2 compares ERp18 KO cells to ERp18 KO cells that have been transfected with ERp18 (RV).   Normalised BiP levels from (D ) were quantified. Error bars represent ± standard deviation for three independent experiments.   ",
    "ncbi_link": "ERp18: 51060"
  },
  {
    "caption": " Levels of ERp72 protein in wild type or ERp18 KO cells before and after ER stress induction with thapsigargin (TG). Panel 1 compares wild type and ERp18 KO cells as indicated. Panel 2 compares ERp18 KO cells to ERp18 KO cells that have been transfected with ERp18 (RV).   Normalised ERp72 levels from (F) were quantified. Error bars represent ± standard deviation for three independent experiments.   ",
    "ncbi_link": "ERp18: 51060"
  },
  {
    "caption": " A, B Wild type and ERp18 KO cells stably expressing ATF6α were treated with 5 µM TG for the indicated times. Cells were then subject to differential centrifugation to obtain membrane (A) and nuclear fractions (B) which were separated by SDS-PAGE under reducing conditions and analysed by western blotting for ATF6α. The positions of full-length ATF6α (ATF6-FL), cleaved membrane-associated ATF6α (ATF6-P) and nuclear translocated S2P cleaved ATF6α (ATF6-N) are as indicated. HDAC2 was used as a nuclear marker. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " (C) ATF6α was immunoisolated from wild type or ERp18 KO cells expressing ATF6α. Samples were separated by SDS-PAGE and ATF6α was detected by western blotting. HC indicates immunoglobulin heavy chains. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " (D, E) Blots of membrane and nuclear fractions respectively from ERp18 KO cells overexpressing ATF6α, either untreated (-) or treated (+) with 30 µM PF429242 (S1P inhibitor) prior to and following induction of ER stress with 10 mM DTT. The positions of ATF6-P, ATF6-M and ATF6-N are as indicated. The unprocessed ER-localised ATF6α (designated ER) and the O-linked glycan modified Golgi-translocated ATF6α (designated G) are indicated. HDAC2 was included as a nuclear marker. The blots in (D, E) confirm that ATF6-P is produced independently of S1P and also the absence of ATF6α processing to ATF6-N in the presence of the S1P inhibitor. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " HEK293T cells stably overexpressing wild type ATF6α or a D564G mutant were treated with 10 mM DTT as indicated to induce ER stress in the presence of the S1P inhibitor. Cell lysates were prepared, separated by SDS-PAGE and then probed with anti-ATF6α. Blot reveals the presence of O-linked glycan modified Golgi-translocated ATF6 (designated G), which is absent for the D564G mutant, confirming a lack of ER to Golgi trafficking. ",
    "ncbi_link": "ATF6α: 22926"
  },
  {
    "caption": " Wild type and ERp18 KO cell lines stably expressing ATF6α D564G were either left untreated (-) or treated (+) with 5 µg/ml brefeldin A for1 h prior to cell lysis. The anti-ATF6α western blot of membrane fractions reveals proteolytic processing by S1P to produce ATF6-M, only in the brefeldin A treated cells. Nuclear fractions confirm the presence of S2P cleavage product, ATF6-N following brefeldin A treatment. Anti-HDAC2 was used as a loading control for the nuclear fraction. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " A-C Wild type cells stably expressing ATF6α (A) or ERp18 KO cells stably expressing ATF6α (B), and ERp18 KO cells stably expressing ATF6α transiently transfected with ERp18 (RV cells) (C), were pre-treated with 30 µM PF429242 (S1P inhibitor) for 1 h prior to induction of ER stress with 10 mM DTT as indicated. ",
    "ncbi_link": "ATF6α: 22926
ERp18: 51060"
  },
  {
    "caption": " D-F Wild type cells transiently expressing ATF6 C467A (D), ATF6 C618A (E), or ATF6 DM (F) were treated as above. Whole cell lysates were separated by SDS-PAGE under reducing conditions and analysed by western blotting for ATF6α. The positions of unprocessed ER-localised ATF6α (ER) and the O-linked glycan modified Golgi-translocated ATF6α (Gol) are indicated as is ATF6-P. ",
    "ncbi_link": "ATF6: 22926"
  },
  {
    "caption": "(B) Western blot analysis of Atxn1 levels in cerebellar granule neurons (CGNs) after knockdown of Zbtb7a  and/or Zbtb7b  (n = 3). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "Zbtb7a: 16969
Zbtb7b: 22724"
  },
  {
    "caption": "(C)  Western blot  analysis of Atxn1 levels in the  cerebella of wild-type (n = 3), Zbtb7a+/- (n = 4), Zbtb7b+/- (n = 3), Zbtb7a+/-;  Zbtb7b+/- (n = 4)  mice. Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "Zbtb7a: 16969
Zbtb7b: 22724"
  },
  {
    "caption": "(D)  Western blot analysis of Atxn1  levels in CGNs after overexpressing Zbtb7a and/or  Zbtb7b (n = 3). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "Zbtb7a: 16969
Zbtb7b: 22724"
  },
  {
    "caption": "(E) Genetic   interaction   of wild-type  human ATXN1(30Q) with either  ZBTB7A or ZBTB7B expressed in the Drosophila eyes. Co-expression of ATXN1(30Q) with ZBTB7A or ZBTB7B severely disrupted the external Drosophila eye structure and increased ATXN1  levels. Scale bar: 100 μm",
    "ncbi_link": "ATXN1: 6310
ZBTB7A: 51341
ZBTB7B: 51043"
  },
  {
    "caption": "(C) Western blot analysis of ATXN1 levels after overexpression of ZBTB7B wild-type (WT), zinc-finger domain mutant (ZFmut) or BTB domain mutants (BTBmut1 and BTBmut2) (n = 3). Data information: Mean ± SD, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "ZBTB7B: 51043"
  },
  {
    "caption": "(D)  qRT-PCR  results of Atxn1 mRNA levels in the cerebella of wild-type (n = 3), Zbtb7b+/- (n = 4), and Zbtb7b-/- mice (n = 4). Data information: Mean ± SD, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "Atxn1: 20238
Zbtb7b: 22724"
  },
  {
    "caption": "(E) MA plot (M: log ratio; A: mean average) of the differentially expressed genes (DEG) analysis from RNA-seq  samples of the cells overexpressing either WT or ZFmut ZBTB7B. Four filters and the number of genes kept after applying each filter are described. Two genes that passed the 4th filter are labeled.",
    "ncbi_link": "ZBTB7B: 51043"
  },
  {
    "caption": "(G) qRT-PCR results of  RSK3 mRNA levels across different CRISPR  knockout cell lines (n = 2). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "CRISPR: 
RSK3: 6196"
  },
  {
    "caption": "(H) Epistatic relationship between ZBTB7B and  RSK3  in terms of ATXN1 regulation. ATXN1 levels were measured after overexpression of ZBTB7B in the RSK3 knockout cell line (sgRSK3) and control cell lines (WT and sgControl) (n = 3). ZBTB7B+RSK3: co-overexpression of both ZBTB7B and RSK3. Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "RSK3: 6196
ZBTB7B: 51043"
  },
  {
    "caption": "(I) qRT-PCR results of RSK3 mRNA levels  after knockdown of ZBTB7B in Daoy  cells (n = 2). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "RSK3: 6196
ZBTB7B: 51043"
  },
  {
    "caption": "(J) qRT-PCR  results of  Rsk3 mRNA levels in the cerebella  of Zbtb7b conditional knockout mice (n = 6). Data information: Mean ± SD, *P<0.05, ***P<0.001, ****P<0.0001, two-tailed t-test.",
    "ncbi_link": "Rsk3: 20112
Zbtb7b: 22724"
  },
  {
    "caption": "(K) Position frequency matrix of ZBTB7B binding DNA sequence and a table of the predicted ZBTB7B binding sites on human RSK3 promoter. Start and End position numbers are described based on TSS. The seventy base pairs upstream  RSK3 promotor includes top two potential binding sites and was used for luciferase assays. Data information: Mean ± SD, *P<0.05, ***P<0.001, ****P<0.0001, two-tailed t-test.",
    "ncbi_link": "RSK3: 6196
ZBTB7B: 51043"
  },
  {
    "caption": "(L) Luciferase assay result of  RSK3  promoter in HEK 293T and HeLa cells transfected with either an empty or ZBTB7B expressing vector (n = 3). Data information: Mean ± SD, *P<0.05, ***P<0.001, ****P<0.0001, two-tailed t-test.",
    "ncbi_link": "RSK3: 6196
ZBTB7B: 51043"
  },
  {
    "caption": "(A) Western blot analysis of ATXN1 after knockdown of RSK3 in Daoy  cells. Bottom left panel: qRT-PCR results of RSK3 mRNA. Bottom right panel: densitometry of the western blot image in the top panel (n = 3 except for shATXN1 where n = 1). Data information: Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "ATXN1: 6310
RSK3: 6196"
  },
  {
    "caption": "(B) Western blot  analysis of ATXN1 after overexpression of RSK3, ZBTB7B, or eGFP in Daoy cells (n = 3). Data information: RSK3 antibody used in is only suitable for detecting overexpressed RSK3 but not for endogenous RSK3. Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "eGFP: 
RSK3: 6196
ZBTB7B: 51043"
  },
  {
    "caption": "(C)  Western blot  analysis of  ATXN1(82Q) after overexpression of either wild-type or inactive RSK3 in Daoy  cells expressing  ATXN1(82Q) (n = 3). Data information: RSK3 antibody used in is only suitable for detecting overexpressed RSK3 but not for endogenous RSK3. Mean ± SD, *P<0.05, **P<0.01, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "ATXN1: 6310
RSK3: 6196"
  },
  {
    "caption": "(A)  Images of  Drosophila eyes expressing  human ATXN1(82Q) with either knockdown or overexpression of the Drosophila RSK3 homolog Sk6II. Scale bar: 100 μm (top) and 20 μm (bottom).",
    "ncbi_link": "ATXN1: 6310
RSK3: 33139
Sk6II: 33139"
  },
  {
    "caption": "(B) Improvement of motor performance by the knockdown of Sk6II  in  Drosophila SCA1 model expressing ATXN1(82Q) in the central nervous system. Mean ± SEM, *P < 0.05, Linear mixed-effect model ANOVA, n = 10/genotype, four times of measurements.",
    "ncbi_link": "ATXN1: 6310
Sk6II: 33139"
  },
  {
    "caption": "(C) A representative  image of a  mouse brain  4 weeks after AAV injection of shRsk3 into 12 weeks old SCA1 mice (Atxn1154Q/2Q) cerebellum. Scale bar: 2 mm.",
    "ncbi_link": "Atxn1: 20238
Rsk3: 20112"
  },
  {
    "caption": "(D)  Western blot analysis of wild-type (2Q) and mutant Atxn1 (154Q) in the cerebella of 16 weeks old SCA1 mice  dissected 4 weeks after the stereotaxic injection of AAV9 harboring shControl (n = 3), shRsk3 (n = 3), or shAtxn1 (n = 2). Mean ± SD, *P<0.05, ***P<0.001 ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "Atxn1: 20238
Rsk3: 20112"
  },
  {
    "caption": "(E) Western blot  analysis of wild-type (2Q) and mutant  Atxn1 (154Q) in the  brainstem  (BS) and  cerebella (CBM) of 8 weeks old Atxn1154Q/2Q (n = 6) and Atxn1154Q/2Q;  Rsk3+/- mice (n = 7). Mean ± SD, *P<0.05, **P<0.01, two-tailed t-test.",
    "ncbi_link": "Atxn1: 20238
Rsk3: 20112"
  },
  {
    "caption": "(F) Rotarod motor performance test result of Atxn1154Q/2Q; Rsk3+/- mice at 11-12 weeks old. Mean ± SEM, *P<0.05, two-way ANOVA, n = 35, 31, 34, 38 for WT, Rsk3+/-, Atxn1154Q/2Q, Atxn1154Q/2Q; Rsk3+/- genotype, respectively.",
    "ncbi_link": "Atxn1: 20238
Rsk3: 20112"
  },
  {
    "caption": "(B) Representative BaseScope assay images of Rsk3 in the whole brain sagittal sections of wild-type (top) and Rsk3-/- mice (bottom) at 5-6 weeks old. The areas within the black squares are magnified in the right panels in each genotype. Scale bar = 2 mm in whole  brain images; 50 μm in the magnified images. Data information:  BS: brainstem, CBM: cerebellum",
    "ncbi_link": "Rsk3: 20112"
  },
  {
    "caption": "(C) Representative  IF images  of Msk1 in the whole brain sagittal  sections of wild-type (top) and Msk1-/- mice  (bottom) at 6 months old. The areas within the white squares are magnified in the right panels in each genotype. Scale bar = 2 mm in whole brain images; 50 μm in the magnified images. Data information: BS: brainstem, CBM: cerebellum",
    "ncbi_link": "Msk1: 73086"
  },
  {
    "caption": "(G) Kaplan-Meier survival  graphs of SCA1 mice with heterozygous knockout of either one or both kinases. The data of Msk1+/-, Rsk3+/-, and Msk1+/-; Rsk3+/- mice overlap those of wild-type mice. *P<0.05, Gehan-Breslow-Wilcoxon test, n = 15, 15, 12, 13, 22, 11, 20, 19 following the order of genotypes in the legend on top of the figure, respectively.",
    "ncbi_link": "Rsk3: 20112
Msk1: 73086"
  },
  {
    "caption": "(C) Purified GST‐tagged NixΔTM was cleaved from the GST moiety by thrombin, purified and used for precipitation by GST fusion proteins. Precipitated proteins were analysed by western blotting (WB) with Nix antibodies. Ponceau S staining was used to visualize GST‐fusion proteins.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "(C) Lysates of COS7 cells transfected with Flag‐wt‐Nix or the indicated mutants were incubated with immobilized GST‐LC3A. The coprecipitated proteins were detected by western blotting (WB) with Flag antibodies. BNIP3, Bcl2/E1B 19kDa‐interacting protein 3‐like protein; Dr, Danio reio; GST, glutathione‐S‐transferase; Hs, Homo sapiens; LIR, LC3‐interacting region; Mm, Mus musculus; wt, wild type; Xl, Xenopus laevis.",
    "ncbi_link": "Nix: 665"
  },
  {
    "caption": "Nix recruits EGFP‐GABARAP‐L1 to stressed mitochondria in reconstituted Nix−/− MEFs. Nix−/− MEFs cotransfected with EGFP‐GABARAP‐L1 and wt‐Nix (A), or Nix‐W35A (B), were incubated with and without mitochondrial poison CCCP for 3 h. Cells were then fixed and analysed for colocalization between EGFP‐GABARAP‐L1 and Nix (stained with Flag antibodies). The final panel in each row shows colocalization between Flag‐Nix‐Cy3 and GABARAP‐L1 using the 'colocalization' highlighter plug‐in for ImageJ software (NIH, Bethesda, MA, USA).",
    "ncbi_link": "Nix: 12177
GABARAP‐L1: 56486"
  },
  {
    "caption": "(A) Flow cytometry of reticulocyte‐enriched blood, cultured in vitro for 3 days, stained with MTR. The blood was taken from mice transplanted with Nix−/− bone marrow and reconstituted with wt‐Nix and Nix‐W35A viruses. Reticulocytes were induced by phenylhydrazine treatment. The viruses also express GFP.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "(B) Mitochondrial clearance in the GFP‐positive fraction of the reticulocyte‐enriched blood, as described in panel (A). Mice were reconstituted with wt‐Nix, LIR‐W35A or empty vector viruses. Data from Nix−/− and Nix+/+ mice are shown for comparison.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "(C) Anti‐Flag, anti‐GFP and anti‐β‐actin western blots of fetal liver cells transduced with Flag‐Nix and Flag‐W35A‐Nix viruses, normalized to total protein. GFP, green fluorescent protein; LIR, LC3‐interacting region; MTR, MitoTracker Red; wt, wild type.",
    "ncbi_link": "Nix: 12177"
  },
  {
    "caption": "a, Etoposide-treated Atg5 -/- MEFs were assessed by EM (left) and by Lamp2immunofluorescence (IF; middle). Right: reverse Lamp2 immunofluorescence image merged with the electron microscopy image. Arrows indicate Lamp2-positive autolysosomes. Magnified photos are provided in Supplementary Fig. 5",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, The size of each autophagic vacuole (AV) (n = 30 cells) in MEFs treated with etoposide. The total number of AVs in 30 cells was 483 in WT cells and 494 in Atg5-/- cells.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, e, Representative macroautophagy in etoposide-treated Atg5-/- MEFs. Conventional (d) and quick freezing and freeze-substitution (e) techniques were used. The autolysosomes (arrows) contain multilamellar bodies (arrowheads).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, c, Punctate GFP-LC3 fluorescence in WT MEFs but not in Atg5-/- MEFs. b, Representative photographs. c, Graphical presentation of the percentages of WT MEFs and Atg5-/- MEFs with punctate GFP-LC3 fluorescence.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, c, Punctate GFP-LC3 fluorescence in WT MEFs but not in Atg5-/- MEFs. b, Representative photographs. c, Graphical presentation of the percentages of WT MEFs and Atg5-/- MEFs with punctate GFP-LC3 fluorescence.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, The same GFP-LC3-transfected Atg5-/- MEFs were assessed by IF and by EM. The magnified photo is the area indicated by the squares. Arrows indicate AVs.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "e, Atg5-/- MEFs were incubated without (NT) or with etoposide and immunostained with an anti-Lamp2 antibody (green). Nuclei were counterstained (red). The percentages of cells with punctate Lamp2 immunostaining are shown (means ± s.d., n = 4).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "f, Microarray analysis of the Atg5-/- MEFs during treatment with etoposide.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "g, h, Induction of Ulk1 in the etoposide-treated Atg5-/- MEFs was assessed by qPCR (g) and by immunoblotting (h).",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "i-l, Atg5-/- MEFs were transfected with the siRNAs related to the Ulk1 complex (i, j) for 24 h and treated with etoposide for 18 h. Induction of macroautophagy was assessed by Lamp2 IF (i, k)",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "i-l, Atg5-/- MEFs were transfected with the siRNAs related to the Ulk1 complex (i, j) for 24 h and treated with etoposide for 18 h. Induction of macroautophagy was assessed by EM (j, l).",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "i-l, Atg5-/- MEFs were transfected with the siRNAs related to the PI(3)K complex (k, l) and a beclin 1 plasmid (k) for 24 h and treated with etoposide for 18 h. Induction of macroautophagy was assessed by Lamp2 IF (i, k).",
    "ncbi_link": "Atg5: 11793
beclin 1: 56208"
  },
  {
    "caption": "i-l, Atg5-/- MEFs were transfected with the siRNAs related to the PI(3)K complex (k, l)for 24 h and treated with etoposide for 18 h. Induction of macroautophagy was assessed by EM (j, l).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "a-d, Electron micrographs of etoposide-treated Atg5-/- MEFs. a, AVs were observed near the Golgi apparatus (G). Inset, the isolation membrane (I) was extended from the Golgi stack. b, Developing autophagosome. rER, rough endoplasmic reticulum. c, d, Isolation membrane fusing with vesicles containing thick membrane (d) and a complete autophagosome (c) is generated.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "e, f, Co-localization of Lamp2 with GFP-M6PR, GFP-Stx7 or GFP-Rab9 in etoposide-treated Atg5-/- MEFs. Arrows indicate co-localized dots. Original magnification, × 200.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "g-i, Atg5-/- MEFs were transfected with the indicated siRNAs for 24 h and treated with etoposide. Induction of macroautophagy was assessed by Lamp2 IF (g) and by EM (h), and the number of isolation membranes was calculated (i). In g, error bars indicate s.d. (n = 4). In h and i, red and blue lines indicate means and s.e.m., respectively; n = 35 cells each.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "j, No effect of silencing of Rab9 (siRab9) on the production of LC3-II in etoposide-treated WT MEFs.",
    "ncbi_link": "Rab9: 56382"
  },
  {
    "caption": "a-e, Typical autophagic structures in the tissues of an Atg5-/- embryo (E14.5): a, midbrain; b-d, liver; c, d, developing autophagosomes; e, heart. Arrows indicate the autophagic vacuoles.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "f, g, k, l, Electron micrographs of wild-type (WT) and Atg5-/- (KO) reticulocytes (f, g) and erythrocytes (k, l). An isolation membrane (asterisk), autophagosomes (arrows) and autolysosomes (arrowheads) are shown. Inset, engulfed mitochondria.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "f, g, k, l, Electron micrographs of wild-type (WT) and Atg5-/- (KO) reticulocytes (f, g) and erythrocytes (k, l). An isolation membrane (asterisk), autophagosomes (arrows) and autolysosomes (arrowheads) are shown. Inset, engulfed mitochondria.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Brains of the 'rescued' mice (Becn1−/−; Becn1EGFP/+) and of control Becn1+/+ littermates were lysed and subjected to immune isolation using an anti-GFP antibody. Proteins bound to anti-GFP antibody were isolated, detected and identified by SDS-PAGE, Coomassie brilliant blue staining and mass spectrometry. Seven bands pulled down by anti-GFP antibody specifically from 'rescued' mice lysate are numbered (this is a copy of image from our previous report with modification).",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(e) The deficiency of Atg14L impairs the protein interaction between Beclin 1 and NRBF2. NIH3T3 cells were transfected with Atg14L or NRBF2 RNAi for 72 h, respectively, and then were lysed and subjected to IP using Beclin 1 antibody. The immunoprecipitants were immunoblotted using the indicated antibodies.",
    "ncbi_link": "Atg14L: 100504663
NRBF2: 641340"
  },
  {
    "caption": "(b) NRBF2 KO MEFs were transfected with CFP, NRBF2-CFP, dMIT-CFP or dCCD-CFP for 48 h. Atg14L-linked Vps34 was pulled down by an anti-Atg14L antibody and subjected to KA. IP products and inputs were immunoblotted using the antibodies indicated. (c) Quantification of IPed Vps34 kinase activity (PI(3)P), Vps34 and Vps15 protein versus IPed Atg14L protein. (Data are shown as mean±s.e.m., P values are indicated on the figures, multiple t-test are followed by Bonferroni correction, n=4 (otherwise indicated, n means number of independent experiments; NS, not significant)).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(d) Overexpression of NRBF2 enhances Atg14L-linked Vps34kinase activity. HEK293T cells were co-transfected with Myc-Vps34-Vps15-His and Flag-Atg14L in the presence of CFP or NRBF2-CFP. Atg14L-linked Vps34 is pulled down by an anti-Flag antibody and subjected to KA (upper panel). IP products and inputs were immunoblotted using the antibodies indicated (upper panel). (e) Quantification of Vps34kinase activity (lower panel) shows the significant difference between two groups. (Data are shown as mean±s.e.m., P value is indicated on the figures, one sample t-test versus hypothetical mean 1, n=5).",
    "ncbi_link": "NRBF2: 29982"
  },
  {
    "caption": "(a) Starvation-induced long-lived protein degradation is impaired after NRBF2 knockdown. Compared with control (con) siRNA, NRBF2 siRNA decreases long-lived protein degradation (proteolysis rate) in NIH3T3 cells under starvation (ST) condition. This difference is diminished when the starved cells are co-treated with wortmannin (WM, 100 nM). (Data are shown as mean±s.e.m., P values are indicated on the figures, one-way analysis of variance with Dunnett as post hoc test, n=4; NS, not significant).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(b) Rapamycin (Rap)-induced autophagy is impaired in the NRBF2 KO cells. The MEFs were treated with (dimethyl sulfoxide) DMSO or 50 μg ml−1 of Rap for 4 h then the cell lysates were immunoprobed with anti-LC3 and anti-p62 antibodies. (c) LC3-II and p62 levels were quantified and normalized with β-actin. Quantification results show that Rap-induced LC3 lipidation (upper) and p62 degradation (lower) were markedly impaired in the NRBF2 KO MEFs. (Data are shown as mean±s.e.m., P values are indicated on the figures, one sample t-test (WT con versus KO con) or unpaired t-test (WT Rap versus KO Rap)). p62 blots quantification, n=6; LC3 blots quantification, n=3).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(h) The NRBF2 KO MEFs were transfected with CFP, NRBF2-CFP, dMIT-CFP or dCCD-CFP for 24 h and then followed by co-immunostaining with GFP and WIPI2 antibodies. (i) The WIPI2 puncta number per cell in GFP-positive cells were counted and quantified. (Data are shown as mean±s.e.m., P values are indicated on the figures, independent samples Kruskal-Wallis test followed by pairwise comparisons, n=30 randomly selected cells, a representative result from two independent repeats). Scale bars, 20 μm, or length indicated on the figure. CM, culture medium.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(a) NRBF2 KO MEFs display impaired autophagosome acidification. WT and NRBF2 KO MEFs are transiently transfected with mCherry-GFP-LC3B. WT MEFs expressing mCherry-GFP-LC3B contain many red-only puncta along with yellow (presence of both red and green) puncta. The number of both red-only puncta and yellow puncta markedly increases after rapamycin (Rap; 50 μg ml−1, 4 h) or starvation (HBSS, 4 h) treatment, suggesting the increased autophagolysosomes and nascent autophagosomes. In contrast, NRBF2 KO MEFs expressing mCherry-GFP-LC3B contain quite fewer red-only puncta and yellow puncta, even after Rap or starvation treatment. (b) The quantification results show that both the numbers of red-only puncta and percentage of red-only puncta (verses total puncta) in KO MEFs were markedly reduced. (Data are shown as mean±s.e.m., P values are indicated on the figures, Mann-Whitney U-test, n=20 randomly selected cells, a representative result from three independent repeats), indicating both the autophagolysome number and autophagosome acidification rate are reduced in KO cells. Scale bars, 20 μm or 10 μm (amplified regions).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(c) Autophagolysome formation is impaired in NRBF2 KO MEFs. WT and NRBF2 KO MEFs were transiently transfected with RFP-LC3 then stained with LAMP2 antibody. The co-localization between RFP-LC3 and LAMP2 are illustrated by line profile. RFP-LC3 puncta recruit much stronger LAMP2 signal in WT MEFs than in NRBF2 KO MEFs (as indicated by white arrows), suggesting the impairment of autophagolysosome formation in KO cells. Scale bars, 20 μm or 10 μm (amplified regions). This is a representative image from three independent experiments.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(d) Overexpression of NRBF2 enhances UVRAG-linked Vps34 kinase activity. HEK293T cells were co-transfected with Myc-Vps34-Vps15-His and FLAG-UVRAG, in the presence of CFP or NRBF2-CFP. UVRAG-linked Vps34 was pulled down by an anti-FLAG antibody and subjected to KA. IP products and inputs are immunoblotted using the antibodies indicated. (e) Quantification of Vps34 kinase activity normalized with immunoprecipitated Vps34 shows the significant difference between two groups. (Data are shown as mean±s.e.m., P value is indicated on the figures, one sample t-test versus hypothetical mean 1, n=5).",
    "ncbi_link": "NRBF2: 29982"
  },
  {
    "caption": "(b) The haematoxylin and eosin (HE) and CD45 staining of 10-month-old WT and NRBF2 KO mice livers. The NRBF2 KO liver shows mild increase of ductular reaction (yellow arrow) and isolated necrosis (red arrows). The necrotic foci were further confirmed by CD45 staining (black arrow). This is a representative image from four mice per genotype. Scale bar, 50 μm. (c) The number of necrotic foci and ductular reaction scores were recorded under bright-field microscope. At least 10 randomly selected fields (10 × ) from each mouse and four mice per genotype were analysed. (Data are shown as mean±s.e.m., P values are indicated on the figures. Ductular reaction scores, unpaired Student's t-test; necrotic foci, Mann-Whitney U-test, n=4 mice each group). BD, bile duct; CV, central vein; PV, portal vein.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(a) WB analysis shows accumulation of p62 in the liver of NRBF2 KO mice. Liver lysates were immunoprobed with antibodies indicated. p62 protein levels are upregulated in the KO mouse liver. (b) The quantification result shows that the p62 level increased more than threefold in the NRBF2 KO miceliver compared with WT miceliver. (Data are shown as mean±s.e.m., P values are indicated on the figures, unpaired Student's t-test; WT, n=5 mice; KO, n=4 mice).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(c) WB analysis shows accumulation of high-molecular weight (HMW) ubiquitin in the liver of NRBF2 KO mice. Insoluble fractions of liver lysates were immunoprobed with an anti-ubiquitin antibody, n=4 mice per genotype.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(d) Atg14L-linked Vps34kinase activity is impaired in the mice of NRBF2 KO mice. Atg14L-linked Vps34 is pulled down by an anti-Atg14L antibody and is subjected to KA. IP products and inputs were immunoblotted using the antibodies indicated. (e) Quantification of IPed Vps34kinase activity versus IPed Atg14L shows the significant difference between WT and NRBF2 KO miceliver. (Data are shown as mean±s.e.m., P values are indicated on the figure, unpaired Student's t-test, n=4 mice each group).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(f) Focal accumulation of p62 in the liver of NRBF2 KO mice. Liver frozen sections (15 μm in thickness) were stained with an anti-p62 antibody. Focal accumulation of p62 is observed in the KO mice liver but not in the WT mice liver. Scale bars, 100 μm or 20 μm (amplified regions). This is a representative image from four mice per genotype.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "WT and NRBF2 KO MEFs were treated with DMSO, 1 μM thapsigargin(TP) or 1 μM tunicamycin (TN) for 24 or 48 h. (a) Then cells were either imaged under phase-contrast microscope or (b) stained with propidium iodide (PI) and subjected to cell death rate analysis by flow cytometry. The representative images of cell morphology after treatments and quantitative analysis of PI-positive cells rate show marked increase of cell death in the NRBF2 KO MEFs compared with WT MEFs. (Data are shown as mean±s.e.m., P values are indicated on the figure, unpaired Student's t-test, n=5). Scale bars, 100 μm; Con, control.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(c) Re-introducing NRBF2 to NRBF2 KO MEFs reverses the vulnerability of cells to ER stress. NRBF2-CFP stably expressing cells were established in the NRBF2 KO background. Cells were treated with DMSO or 1 μM TP for 24 h then stained with PI and subjected to cell death rate analysis by flow cytometry. The cell death rate in CFP-positive (+) population (NRBF2-CFP expression) and negative (−) population (no NRBF2-CFP expression) were recorded and analysed, respectively. (Data are shown as mean±s.e.m., P values are indicated on the figure, unpaired Student's t-test, n=3).",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(d) ER stress inducers trigger caspase-8 and caspase-3 activation in NRBF2 KO MEFs. MEFs were treated with DMSO, 1 μM TP or 1 μM TN for 24 h, and then immunoprobed with indicated antibodies. Marked accumulation of cleaved caspase-8 (C-Cas 8; p43 and p18 units) and cleaved caspase-3 (C-Cas 3) are observed in the NRBF2 KO MEFs but not WT MEFs treated with TP or TN. This is a representative image from three independent experiments.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(e) C-Cas 8 preferentially localizes at p62 aggregation foci. MEFs were treated with DMSO or 1 μM TP for 24 h, and then co-stained with an anti-p62 antibody and an anti-cleaved caspase-8 antibody. The C-Cas 8 fluorescence signals are triggered in NRBF2 KO MEFs treated with TP and preferentially localize at p62 aggregation foci. Scale bars, 20 μm. This is a representative image from three independent experiments.",
    "ncbi_link": "NRBF2: 641340"
  },
  {
    "caption": "(a) NRBF2 is critical for the assembly of Vps34-Vps15 and Atg14L-Beclin 1 complex. Brain lysate from WT and NRBF2 KO mice were subjected to co-IP by Vps34 antibody and Atg14L antibody. The IP products were subjected to in vitro lipid KA and WB analysis using the indicated antibodies. (b,c) Quantification results shows that Vps34-Vps15 and Atg14L-Beclin 1 complex interactions as well as Atg14L-linked Vps34 kinase activity are markedly impaired in NRBF2 KO mice. (Data are shown as mean±s.e.m., P values are indicated on the figures, unpaired Student's t-test, n=4 mice in each group; NS, not significant).",
    "ncbi_link": "Atg14L: 100504663
NRBF2: 641340
Vps34: 225326"
  },
  {
    "caption": "(d) Overexpression of NRBF2 enhances overall Vps34kinase activity. HEK293T cells were co-transfected with Myc-Vps34-Vps15-His and CFP, NRBF2-CFP, dMIT-CFP or dCCD-CFP. Total Vps34 was pulled down by an anti-myc antibody and subjected to KA. IP products and inputs are immunoblotted using the antibodies indicated. (e) Quantification of IPed Vps34kinase activity, Vps15 protein normalized with IPed Vps34 shows that NRBF2-CFP, but not CFP, dMIT-CFP or dCCD-CFP significantly enhance Vps34kinase activity and Vps34-Vps15 interaction. (Data are shown as mean±s.e.m., P values are indicated on the figures. IPed Vps15/IPed Vps34, one sample t-test versus hypothetical mean 1, Bonferroni correction, n=3; IPed Vps34kinase activity/IPed Vps34, multiple t-test followed by Bonferroni correction, n=3).",
    "ncbi_link": "NRBF2: 29982"
  },
  {
    "caption": "(B) Ultrastructure of HCV-infected cells showing perinuclear clustering of damaged mitochondria. Control naïve Huh7 cells (left) and stable cells harboring HCV full-length replicon FLR-JFH1 (right) were examined by electron microscopy. In the zoomed images, typical ultrastructure of mitochondria in naïve cells and ultrastructural abnormalities of mitochondria in HCV replicon cells are shown. Organelle mark: N, nucleus; M and white arrow, mitochondria. Scale bar = 1 µM. Fluorescent images (below) indicate the expression of HCV core protein in HCV replicon cells. Cells were immunostained with anti-HCV core antibody (red). Nuclei were stained with DAPI (blue).",
    "ncbi_link": "JFH1: 951476"
  },
  {
    "caption": "(G) Parkin-mediated ubiquitination of Mfn2 and VDAC1 in HCV-infected cells. The ubiquitinated Mfn2 and VDAC1 proteins were analyzed by immunoprecipitation with anti-Mfn2 and VDAC1 antibodies, respectively, followed by immunoblotting with anti-Ub antibody. The protein expression levels of Parkin were analyzed by immunoblotting with anti-Parkin antibody. HCV infection was verified by immunoblotting with anti-HCV core antibody. β-actin was used as an internal loading control. Normal mouse IgG was used as a negative control for immunoprecipitation (IP). (D and E) P values were calculated by using an unpaired Student's t-test.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(A and B) Quantitative analyses of ATF4, Parkin, and PINK1 gene expression in HCV-infected cells. Huh7 cells infected with HCVcc for 5 days or treated with CCCP (10 or 20 µM) for 24 h were used for analysis of ATF4, Parkin, and PINK1 gene expression. (A) Intracellular mRNA levels of ATF4, Parkin, and PINK1 were analyzed by real-time qRT-PCR. GAPDH was used to normalize changes in Parkin and PINK1 gene expression (mean ± SD; n = 3; *p<0.01, **p<0.05). P values were calculated by using an unpaired Student's t-test.",
    "ncbi_link": "ATF4: 468
GAPDH: 2597
Parkin: 5071
PINK1: 65018"
  },
  {
    "caption": ". (D) Ultrastructure of HCV-infected cells showing the formation of mitophagosome. Control naïve Huh7 cells (uninfected), HCV FLR-JFH1 replicon cells, and Huh7 cells infected with HCVcc (Jc1) were examined by electron microscopy. In the zoomed image, the formation of mitophagosome in HCV-infected cells is shown. Organelle mark: N, nucleus; MF, mitophagosome formation. Scale bar = 0.2 µM (uninfected); 0.1 µM (infected).",
    "ncbi_link": "Jc1: 951475
JFH1: 951476"
  },
  {
    "caption": "(B) Ultrastructure of HCV-infected cells showing the formation of mitophagolysosome. HCV FLR-JFH1 replicon cells were examined by electron microscopy. In the zoomed image, the formation of mitophagolysosome in HCV-infected cells is shown. Organelle marker: ML, mitophagolysosome. Scale bar = 0.1 µM.",
    "ncbi_link": "JFH1: 951476"
  },
  {
    "caption": "A and B) Inhibitory effect of Parkin, PINKI, and ATG5 silencing on HCV replication. Huh7 cells transfected with Non-Targeting (NT) or gene-specific siRNA pools targeting Parkin, PINK1, and ATG5 genes, respectively, were infected with HCVcc. At day 3 post-infection, the levels of HCV RNA (A) and targeted gene mRNA",
    "ncbi_link": "ATG5: 9474
Parkin: 5071
PINK1: 65018
PINKI: 65018"
  },
  {
    "caption": "A (B) were analyzed by real-time qRT-PCR, as described in Materials and Methods (mean ± SD; n = 3; *p<0.01). GAPDH was used to normalize changes in Parkin, PINK1, and ATG5 gene expression.",
    "ncbi_link": "ATG5: 9474
GAPDH: 2597
Parkin: 5071
PINK1: 65018"
  },
  {
    "caption": "(C and D) Rescue of HCV RNA replication by Parkin overexpression. Huh7 cells stably expressing mock vector (M-KD), Non-target-shRNA (NT-KD), and Parkin-shRNA (P-KD), respectively, were infected with HCVcc. P-KD cells were further transfected with two different concentration of the plasmid DNA encoding wild-type Parkin for 2 days before harvest. At 3 days post-infection, intracellular HCV RNA levels were analyzed by real-time qRT-PCR. GAPDH was used to normalize changes in HCV RNA expression (C) (mean ± SD; n = 3; *p<0.01, **p<0.05).",
    "ncbi_link": "GAPDH: 2597
Parkin: 5071"
  },
  {
    "caption": "(D) The expression levels of Parkin and HCV core protein were analyzed by immunoblotting with anti-Parkin and HCV core antibodies. Ectopic expression level of HA-tagged wild-type Parkin was detected by immunoblotting with anti-HA antibody. β-actin was used as an internal loading control. P values were calculated by using an unpaired Student's t-test. The relative intensity of HCV core expression normalized to β-actin was analyzed by ImageJ.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": ". (B) Rescue effect of Parkin knockdown on reduction of mitochondrial complex I enzyme activity caused by HCV infection. NT-KD and P-KD cells infected with HCVcc were harvested on day 3 post-infection and used for analysis of the activity of mitochondrial complex I enzyme (mean ± SD; n = 3; *p<0.05).",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(D) Effect of Parkin silencing on depletion of mitochondrial DNA caused by HCV infection. Huh7 cells transfected with NT or Parkin-specific siRNA pools were infected with HCVcc. At day 3 post-infection, mitochondrial DNA levels of ND-2 and COX-2 were analyzed by real-time qPCR. GAPDH was used to normalize changes in ND-2 and COX-2 gene expression (mean ± SD; n = 3; *p<0.01). (A, B, and D) P values were calculated by using an unpaired Student's t-test.",
    "ncbi_link": "COX-2: 4513
GAPDH: 2597
ND-2: 4536
Parkin: 5071"
  },
  {
    "caption": "A. Intracellular survival of GAS strains 188, 188SLO- (SLO-), and 188NADase- (NADase-). Intracellular CFU were quantified at 2 h, 4 h, 6 h, 8 h, and 24 h, and intracellular survival was calculated as the percent viable CFU compared to 2 h.",
    "ncbi_link": "NADase: 3573139
SLO: 900490"
  },
  {
    "caption": "B. Intracellular survival of GAS strain 188SLO- that was partially complemented from plasmid piSLO (SLO-(piSLO)), strain 188 and 188SLO- that contained the empty complementation vector, 188(pSIV4) and SLO-(pSIV4), respectively.",
    "ncbi_link": "SIV4: 
SLO: 900490"
  },
  {
    "caption": "C. Intracellular survival of GAS strain JRS4, JRS4SLO- (SLO-), and JRS4NADase- (NADase-). Experiments were performed in triplicate and values represent the mean of three independent experiments ± SD. *, P<0.001.",
    "ncbi_link": "NADase: 3573139
SLO: 900490"
  },
  {
    "caption": "A. Confocal microscopy of the association between EGFP-LC3 and GAS strain 188, 188SLO- (SLO-), 188SLS- (SLS-), or 188SLO-SLS- (SLO-SLS-). Immunofluorescent staining distinguished intracellular (Alexa-568, red) from extracellular (Alexa-568 and Alexa-660, red and blue, respectively) GAS. Scale bar = 10 µm. The percent of intracellular GAS that were associated with EGFP-LC3 at 3 h post-infection is shown for each strain.",
    "ncbi_link": "SLS: 3572347
SLO: 900490"
  },
  {
    "caption": "B. Electron microscopy of GAS strains 188, 188SLO-, and 188SLO-SLS- at 3 h post-infection. Arrowheads indicate the presence of double or multiple membranes (188 and 188SLO-) or single membranes (188SLO-SLS-) partially or completely surrounding bacteria. Vacuolar compartments associated with 188 and 188SLO- also contain cytosolic material.",
    "ncbi_link": "SLS: 3572347
SLO: 900490"
  },
  {
    "caption": "C. Intracellular survival of GAS strains 188, 188SLO-, 188SLS-, and 188SLO-SLS-. *, P<0.05.",
    "ncbi_link": "SLS: 3572347
SLO: 900490"
  },
  {
    "caption": "D. Intracellular survival of 188 or 188SLO- in the presence or absence of Beclin1 knockdown.",
    "ncbi_link": "Beclin1: 8678
SLO: 900490"
  },
  {
    "caption": "A. Intracellular survival of GAS strains 188, 188NADase-, and 188NADase(G330D). Deletion of the gene encoding NADase or inactivation of NADase by the amino acid substitution G330D resulted in a 20- to 40-fold reduction in intracellular survival compared to parent strain 188. *, P<0.001.",
    "ncbi_link": "NADase: 3573139"
  },
  {
    "caption": "NADase western blot (B)",
    "ncbi_link": "NADase: 3573139"
  },
  {
    "caption": "and activity measurements (C) of culture supernatants from GAS strains 188, 188NADase-, and 188NADase(G330D).",
    "ncbi_link": "NADase: 3573139"
  },
  {
    "caption": "A. Confocal microscopy demonstrating the association between ubiquitin (green) and intracellular GAS (red) at 30 min post-infection in keratinocytes infected with GAS strain 188, 188SLO-, 188NADase-, or 188SLO(Y255A). Extracellular GAS were stained blue and red for identification as described in Figure 2. Scale bar = 10 µm. The percentage of intracellular GAS that were associated with ubiquitin is indicated for each strain, based on quantification of at least 100 bacteria in three independent experiments.",
    "ncbi_link": "NADase: 3573139
SLO: 900490"
  },
  {
    "caption": "B. Hemolytic activity of culture supernatants of GAS strain 188, 188SLO-, and 188SLO(Y255A). The amino acid substitution Y255A in SLO abrogates the ability of SLO to porate the host cell membrane, demonstrated by the failure of culture supernatants from 188SLO(Y255A) to lyse erythrocytes despite producing wild-type amounts of the variant SLO protein. Inset, corresponding Western blot for SLO in culture supernatants from these strains.",
    "ncbi_link": "SLO: 900490"
  },
  {
    "caption": ". C. NADase activity in cell culture supernatants and in the cytosol of keratinocytes infected with GAS strain 771, 771SLO-, 771SLO(Y255A), or 771NADase-. Intracellular NADase activity due to translocation by extracellular GAS was identical between 771 and 771SLO(Y255A), but reduced in 771SLO-.",
    "ncbi_link": "NADase: 3573139
SLO: 900490"
  },
  {
    "caption": "D. The intracellular survival of 188SLO(Y255A) was significantly lower than that of its parental strain, 188, and similar to that of 188SLO-. *, P<0.01.",
    "ncbi_link": "SLO: 900490"
  },
  {
    "caption": "E. Confocal microscopy demonstrating the association between galectin 8 (green) and intracellular GAS (red) in keratinocytes infected for 30 min with GAS strain 188, 188SLO-, or 188 SLO-SLS-. Extracellular GAS (GAS(out)) were stained blue and red for identification as described in Figure 2. Scale bar = 10 µm. The percentage of intracellular GAS that were associated with galectin 8 is indicated for each strain, based on quantification of at least 100 bacteria in three independent experiments. 188SLO-SLS- was never associated with galectin 8 (0%).",
    "ncbi_link": "SLS: 3572347
SLO: 900490"
  },
  {
    "caption": "SLO and NADase inhibit lysosomal fusion to GAS-containing autophagosomes in oropharyngeal keratinocytes.A. Confocal microscopy of keratinocytes infected with GAS strain 188, 188SLO-, or 188NADase- demonstrating the association of the lysosomal marker LAMP-1 (red) with GAS (blue) contained within EGFP-LC3 (green)-positive compartments at 1 h, 3 h, and 6 h post-infection. Scale bar = 10 µm. B. Quantification of the percent of GAS within EGFP-LC3-positive compartments that are co-localized with LAMP-1 at 1 h, 3 h, and 6 h. Data represent mean values from three independent experiments in which at least 100 intracellular GAS were quantified for each time point in each experiment.",
    "ncbi_link": "NADase: 3573139
SLO: 900490"
  },
  {
    "caption": "(B) Graph showing the number of neurospheres per P100 cell plate at different steps, as indicated. Nr2f1KO neurospheres proliferate for a longer time (up to 30 passages tested), whereas WT cells exhaust around step 9. n ≥ 3 culture wells from n = 2 batches. Data information: data are represented as means ± SEM. 2-way ANOVA (B) (**P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865"
  },
  {
    "caption": "(J-L) E12.5 dorsal brain views (J,J') and representative sections of posterior hemispheres (K,K'), showing a vesicle enlargement in mutant brains (K'). The extension of the ventricular surface was quantified along the A-P axis (L); red color code represents Nr2f1 gradient in WT brains. 12µm-thick sections were collected on series of 10 slides; consecutive measurement levels are 120µm apart from each other. n ≥ 3 brains. Data information: In graphs, data are represented as means ± SEM. 2-way ANOVA (*P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865"
  },
  {
    "caption": "(N-P) GFP (green; expressed under Sox2 promoter) and RFP (red; expressed under Tis21 promoter) IF of E13.5 lateral pallia, 18-hours after IUE. The proportion of single or double positive NPs is shown in pie charts in (P). n = 3 electroporated brains. Data information: Nuclei (blue) were stained with DAPI. 2-way ANOVA (*P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "GFP: 
RFP: 
Tis21: 12227
Sox2: 20674"
  },
  {
    "caption": "(C) Pax6 and Nr2f1 pixel intensity quantification at E12.5 and E14.5 indicating increased Pax6 levels upon Nr2f1 removal. n ≥ 3 brains. Data information: the pixel intensity was quantified in 100µm-width boxes, randomly placed across the lateral pallium. Data are represented as means ± SEM. 2-way ANOVA (*P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865"
  },
  {
    "caption": "(D) Real time RT-PCR quantification of Nr2f1 and Pax6 expression in E12.5 cortices. n ≥ 3 cortices. Data information: Data are represented as means ± SEM. 2-way ANOVA (*P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(E-G'') GFP (green; electroporated cells), Pax6 (red) and Nr2f1 (blue) IF of pCIG2-Nr2f1-IRES-GFP electroporated brains at E13.5 (24-hours after IUE). VZ (F-F'') and CP (G-G'') regions are shown at high magnification. Arrowheads point to GFP+ electroporated cells over-expressing Nr2f1 (blue in F',G'), down-regulating Pax6 (F'') and rapidly migrating out of the VZ (G-G''). Scale bars: 50µm. SVZ: subventricular zone; VZ: ventricular zone.",
    "ncbi_link": "GFP: 
Nr2f1: 13865"
  },
  {
    "caption": "(H) Scatter plot showing Pax6 and Nr2f1 pixel intensity of VZ electroporated progenitors, comparing Nr2f1 overexpressing cells (orange dots) with control pCIG2-GFP electroporated cells (blue dots). Average Nr2f1 and Pax6 pixel intensities of the 2 populations were compared by 2-way ANOVA and resulted significantly different (***= <0.0001). n = 2 electroporated brains. Data information Data are represented as means ± SEM. 2-way ANOVA *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "GFP: 
Nr2f1: 13865"
  },
  {
    "caption": "(I) Real time RT-PCR of cell cycle genes comparing WT (blue line) and KO (orange line) cortices. CyclinD1 and P21 transcripts are down-regulated whereas Dct is up-regulated in mutants. n = 3 cortices. Data information: Data are represented as means ± SEM. 2-way ANOVA *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "CyclinD1: 12443
P21: 12575
Dct: 13190"
  },
  {
    "caption": "(J-L) GFP (green; electroporated cells) and P21 (red) IF of E14.5 cortex electroporated 48 hours earlier with control PX458 plasmid (J) or CRISPR/Cas9-expressing plasmid directed against Nr2f1 sequence (PX458-αNr2f1; K). Percentage of P21/GFP double positive cells (L). Arrowheads in (J,K) point to P21+ cells. n = 2 electroporated brains. Data information , nuclei (blue) were stained with DAPI. Student t-test (L; *P<0.05",
    "ncbi_link": "Cas9: 
CRISPR: 
GFP: 
Nr2f1: 13865"
  },
  {
    "caption": "(A) Real time RT-PCR analysis of Pax6 expression in neurospheres with different genotypes, as indicated. n = 3 cortices. N KO P HET: Nr2f1 KO, Pax6 HET. Data information: Data are represented as means ± SEM. 2-way ANOVA ; *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(B) Representative images of Nr2f1 KO Pax6 HET neurospheres obtained from E15.5 neocortices and cultured in vitro. Scale bars: 50µm.",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(C) Graph showing the number of neurospheres per P100 cell plate, at different steps, as indicated. While Nr2f1 KO neurospheres (orange line) proliferate for a longer time compared to WT ones (blue line), the loss of one Pax6 allele (gray line) almost restores normal proliferation rate and exhaustion time. Complete Pax6 loss is not compatible with stem cell renewal (yellow line). n ≥ 3 culture wells from n = 2 independent batches. Data information: Data are represented as means ± SEM. 2-way ANOVA ; *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(D-E) Paired cell analysis after neurosphere dissociation and 24-hour culture at clonal density. Couples of dividing cells were identified by Map2 (red; N, neurons) and BLBP (green; P, progenitors) IF. Pie charts in (E) show the proportion of P-P (proliferative; D), P-N (asymmetric differentiative; D') or N-N (symmetric differentiative; D'') couples in WT, Nr2f1KO and Nr2f1KO Pax6HET animals. n ≥ 3 samples from n = 2 culture batches. Data information: Nuclei (blue) were stained with DAPI. Data are represented as means ± SEM. 2-way ANOVA ; *P<0.05, **P<0.01, ***P<0.001 Scale bars: 50µm.",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(F-I) Pax6 (green) and Nr2f1 (red) IF in the posterior-most region of E12.5 cortex, showing Pax6 upregulation in Nr2f1 KO animals (G,G') compared to WT (F',F''). Normal Pax6 levels can be restored by loss of one Pax6 allele (Nr2f1 KO, Pax6 HET; H,H'). n ≥ 3 brains. N KO: Nr2f1 KO; P HET: Pax6 HET. Data information: Nuclei (blue) were stained with DAPI. Scale bars: 50µm.",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "Pixel intensity quantification of Nr2f1 (blue) and Pax6 (orange) is shown in (I). n ≥ 3 brains. N KO: Nr2f1 KO; P HET: Pax6 HET. Data information: the pixel intensity or the number of positive cells was quantified in 100µm-width boxes, randomly placed across the LP. Data are represented as means ± SEM. 2-way ANOVA ; *P<0.05, **P<0.01, ***P<0.001).",
    "ncbi_link": "Nr2f1: 13865
Pax6: 18508"
  },
  {
    "caption": "(I-J) NR2F1 (red) and GFP (green) IF in day 40 human brain organoids upon electroporation of the PX458-αNR2F1 plasmid. In (I,I'), GFP+NR2F1- cells (empty arrowheads) and a GFP+NR2F1+ cell (white arrowhead) are shown; quantification in (J). n ≥ 6 organoids from n = 2 batches. Data information: Nuclei (blue stained with DAPI. the pixel intensity or the number of positive cells were quantified in 100µm-width boxes, randomly placed across the cortex/organoid neuroepithelia In graphs, data are represented as means ± SEM. 2-way ANOVA test (*P<0.05, **P<0.01, ***P<0.001). Scale bars: 50µm.",
    "ncbi_link": "GFP: 
NR2F1: 13865"
  },
  {
    "caption": "(K-M) TUJ1 (red; differentiating neurons) and GFP (green) IF 7 days after electroporation of control (K) and PX458-αNr2f1 plasmids (L). Co-expression of GFP with SOX2 or TUJ1 distinguishes neural progenitors (NPs) from neurons (Ns), as quantified in (M). Arrowheads in (K,L) point to TUJ1+ GFP+ cells. n ≥ 6 organoids from n = 2 batches. Data information: Nuclei (blue stained with DAPI. the number of positive cells was normalized over the total number of GFP+ cells. In graphs, data are represented as means ± SEM. 2-way ANOVA test (*P<0.05, **P<0.01, ***P<0.001). Scale bars: 50µm.",
    "ncbi_link": "Nr2f1: 13865"
  },
  {
    "caption": "K. Heat map of PtdIns, PtdInsP and PtdInsP2 levels from 4 different murine brain regions. The colors from green to red indicate the relative contents of lipid isoforms in different brain regions from NPC1I1061T mice relative to wild-type brains; n=3 for both WT and NPC1I1061T animals.",
    "ncbi_link": "NPC1: 4864"
  },
  {
    "caption": "J. Confocal images of control and U18-treated GFP11-SAC1 HEK293 cells (top) and control and NPC1I1061T patient fibroblasts immunolabeled with anti-SAC1 antibody (bottom). Insets show an enlarged view of SAC1 centered on a perinuclear region. K. Quantification analyses of GFP11-SAC1 (top; Control: n=10; U18: n=10) and anti-SAC1 (bottom; Control: n=7; NPC1I1061T: n=8) mean fluorescence intensities in Golgi normalized to the cytoplasm. ",
    "ncbi_link": "NPC1: 4864"
  },
  {
    "caption": "B, Confocal images of wild-type and PI4KIIα-depleted (sgPI4K2A) HEK293-CAS9 cells expressing P4M-YFP, treated with or without U18. Bottom panels show enlarged views of PtdIns4P in a Golgi region. C, Quantitative analyses of P4M-YFP mean fluorescence intensity distributed in Golgi normalized to the cytoplasm under different conditions. Control: n=19; U18: n=13, sgPI4K2A: n=19; sgPI4K2A+U18: n=17; sgDHHC3: n=11; sgDHHC3+U18: n=11. * represents a significant difference (P<0.05) between control and other non-U18 treated groups; # represents a significant difference (P<0.05) between U18-treated and other U18-treated sgRNA groups.",
    "ncbi_link": "CAS9: 
PI4K2A: 55361
PI4KIIα: 55361
DHHC3: 51304"
  },
  {
    "caption": "H. Control or GFP-DHHC3 expressing tsA201 cells fixed and stained for PI4KIIα or PI4KIIIβ. Bottom panels show enlarged views of DHHC3, PI4KIIα, or PI4KIIIβ at Golgi regions. I. Quantification of PI4KIIα (left; control: n=42, DHHC3: n=24), or PI4KIIIβ (right; control: n=39, DHHC3: n=26) intensity relative to cytoplasm. ",
    "ncbi_link": "GFP: 
DHHC3: 51304"
  },
  {
    "caption": "M. Confocal images of control (top row), NPC1I1061T (middle row), and NPC1I1061T treated with sgDHHC3 (bottom row) patient cells expressing P4M, LAMP1 and CAS9. Insets are zoomed regions from LAMP1 positive areas. N. Quantification of P4M changes at endomembranes. Control: n=149, U18: n=251, sgPI4KIIa +U18: n=131, sgDHHC3+U18: n= 271. Each n represents a single enodolysosome.",
    "ncbi_link": "CAS9: 
NPC1: 4864
PI4KIIa: 55361
DHHC3: 51304"
  },
  {
    "caption": "C. Confocal images of control and NPC1I1061T patient fibroblasts immunolabeled for ACBD3. Black and orange squares show expanded views of anti-ACBD3 in Golgi and endomembrane compartments, respectively. D. Analyses of ACBD3 intensity distributed in Golgi (left graph; Control: n=9; NPC1I1061T: n=9) or in endomembranes (right graph; Control: n=1360; NPC1I1061T: n=1645 from 15 cells), normalized to the cytoplasm.",
    "ncbi_link": "NPC1: 4864"
  },
  {
    "caption": "I. Confocal images of control and sgACBD3 HEK293-CAS9 cells expressing P4M-YFP, treated with or without U18. Bottom panels show enlarged views of PtdIns4P in Golgi and in endomembrane compartments. J. Quantitative analyses of P4M-YFP mean fluorescence intensity at Golgi (left graph) or endomembranes (right graph) normalized to the cytoplasm. * represents a significant difference (P<0.05) between control and other non-U18 treated groups; # represents a significant difference (P<0.05) between U18-treated and other U18-treated sgRNA groups. For left graph; Control: n=19; U18: n=13; sgPI4K3B: n=12; sgPI4K3B+U18 : n=11; sgPI4K2A + sgPI4K3B: n=12; sgPI4K2A + sgPI4K3B +U18: n= 12; sgACBD3: n=15; sgACBD3+U18: n=16. For right graph; control: n=149; U18: n=251; sgACBD3: n=138; sgACBD3+U18: n=190. Please note that 'control' and 'U18' datasets in Fig 5J are identical to those in Fig. 4C. Data for all CRISPR experiments were collected on the same days.",
    "ncbi_link": "CAS9: 
PI4K3B: 
ACBD3: 64746
PI4K2A: 55361"
  },
  {
    "caption": "A. Confocal images of control, NPC1I1061T and ACBD3-deleted NPC1I1061T patient fibroblasts expressing P4M-YFP. Black and orange squares show expanded views of PtdIns4P in Golgi and endo/lysosomal compartments respectively.",
    "ncbi_link": "ACBD3: 64746
NPC1: 4864"
  },
  {
    "caption": "C. Confocal images of control, NPC1I1061T and ACBD3-deleted NPC1I1061T patient fibroblasts immunolabeled with mTORC1 antibody. Bottom images show expanded views of mTORC1 immunolabeling in the regions indicated by the dashed squares in the main images. White dashed lines represent the outline of each cell. D. Quantification of mTORC1 mean integrated density normalized bycell area in control, NPC1I1061T and ACBD3-deleted NPC1I1061T patient fibroblasts. Control: n=15; NPC1I1061T: n=14; NPC1I1061T+sgACBD3: n=11.",
    "ncbi_link": "ACBD3: 64746
NPC1: 4864"
  },
  {
    "caption": "A. Confocal images of control and NPC1I1061T patient fibroblasts immunolabeled for Giantin and CI-M6PR. Insets show expanded views of each immunolabeling in the Golgi region (upper insets) or centered on endomembranes (bottom inset, merged signals). Dashed grey and white lines represent the outline of each cell. B. Analysis of the mean area of M6P and Giantin colocalizing puncta (top graph; Control: n=23; NPC1I1061T: n=18) and of their mean fluorescence intensity (bottom graph; Control: n=18; NPC1I1061T: n=18) in control and NPC1I1061T patient fibroblasts. ",
    "ncbi_link": "NPC1: 4864"
  },
  {
    "caption": "C. Confocal images of control and NPC1I1061T patient fibroblasts expressing ARF1-GFP. Insets show enlarged views of ARF1 in the Golgi area. Tubular structures were observed in NPC1I1061T patient fibroblasts as indicated by the black arrows. D. Quantification of ΑRF-1 fluorescence intensity in Golgi normalized to the cytoplasm in control and NPC1I1061T patient fibroblasts. Control: n=10; NPC1I1061T: n=11. ",
    "ncbi_link": "NPC1: 4864"
  },
  {
    "caption": "B COS‐1 cells were treated with ATP8A1 siRNAs for 72 h. Cell lysates were prepared and then immunoblotted with anti‐ATP8A1 antibody. α‐tubulin was used as a loading control.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "C, D COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h. siRNA‐resistant GFP‐ATP8A1 (WT or E191Q) and myc‐CDC50A were transfected 48 h after siRNA transfection. Cells were pulsed with Alexa 594‐Tfn and chased in medium with unlabeled Tfn. During the chase, cells were imaged every 6 min for 54 min. The fluorescence intensity of Alexa 594‐Tfn is shown as percentage of that at 0 min (mean ± SEM, n = 4-6; ***P 0.001; Student's t‐test). See Supplementary Fig S2 for the representative images.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "E, F COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h. Cells were pulsed with Alexa 594‐CTxB for 5 min and chased for 15 or 60 min. Cells were then fixed and stained for GM130. In (E), representative images are shown. In (F), the Pearson's coefficient between CTxB and GM130 after 60‐min chase is shown. Data represent mean ± SD (n > 26 cells from three independent experiments). ***P 0.001; two‐tailed Student's t‐test. Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "A COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h and stained for TfnR. Each image represents the maximum intensity z‐projection of four confocal slices. Intensified images are shown in the bottom row. Red dashed lines and arrowheads indicate nuclei and TfnR puncta, respectively. Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "B COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h and stained for the indicated proteins. Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "C COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h. TfnR‐GFP was transfected 48 h after siRNA transfection. Cells were then imaged with an epifluorescent microscope. Selected stills from Supplementary Movie S1 are shown. The asterisks indicate the tips of the tubules of interest. Scale bars, 5 μm.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "D The effect of increasing levels of 1,2‐dioleoyl‐PS on the ATPase activity of purified ATP8A1 (WT and E191Q)‐CDC50A complex. The Km and Vmax for the WT complex were 59.1 ± 3.5 μM and 38.7 ± 0.8 μmol ATP/min/mg protein, respectively.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "E COS‐1 cells were treated with ATP8A1 siRNA1 for 72 h. siRNA‐resistant ATP8A1 (WT or E191Q), and myc‐CDC50A were transfected 48 h after siRNA transfection. Cells were then fixed and stained for TfnR. The graph shows percentages of cells showing aberrant TfnR‐positive tubules as mean ± SD of three independent experiments. At least 50 cells were counted per experiment.",
    "ncbi_link": "ATP8A1: 10396
CDC50A: 55754"
  },
  {
    "caption": "A COS‐1 cells were treated with EHD1 siRNAs for 72 h. Cell lysates were prepared and then immunoblotted with EHD1 antibody. α‐tubulin was used as a loading control.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "B, C Cells were treated with EHD1 siRNA1 for 72 h. Cells were pulsed with Alexa 488‐Tfn and chased in medium with unlabeled Tfn. During the chase, cells were imaged every 3 min for 57 min. In (B), representative images of Alexa 488‐Tfn in control or EHD1‐depleted cells are shown. In (C), the fluorescence intensity of Alexa 488‐Tfn is shown as percentage of that at 0 min (mean ± SEM, n > 3 cells from three independent experiments). ***P 0.001; two‐tailed Student's t‐test. Scale bars, 10 μm.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "B, C Cells were treated with EHD1 siRNA1 for 72 h. Cells were pulsed with Alexa 488‐Tfn and chased in medium with unlabeled Tfn. During the chase, cells were imaged every 3 min for 57 min. In (B), representative images of Alexa 488‐Tfn in control or EHD1‐depleted cells are shown. In (C), the fluorescence intensity of Alexa 488‐Tfn is shown as percentage of that at 0 min (mean ± SEM, n > 3 cells from three independent experiments). ***P 0.001; two‐tailed Student's t‐test. Scale bars, 10 μm.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "D COS‐1 cells were treated with EHD1 siRNA1 for 72 h. Cells were pulsed with Alexa 594‐CTxB for 5 min and chased for 60 min. Cells were then fixed and stained for GM130. The Pearson's coefficient between CTxB and GM130 is shown (mean ± SD, n > 30 cells from two independent experiments). ***P 0.001; two‐tailed Student's t‐test. See Supplementary Fig S7A for the representative images.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "E COS‐1 cells were treated with EHD1 siRNA1 for 72 h and stained for TfnR. The image represents the maximum intensity z‐projection of four confocal slices. Scale bar, 10 μm.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "G Cells were treated with ATP8A1 siRNA1 for 72 h and stained for EHD1. For the rescue experiments, siRNA‐resistant GFP‐ATP8A1 (WT or E191Q) and myc‐CDC50A were transfected 48 h after siRNA transfection. Asterisks indicate cells with GFP‐ATP8A1 expression. The graph represents percentage of cells with perinuclear localization of EHD1 as mean ± SD of three independent experiments (at least 141 cells were counted for each condition). Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "A The effect of various lipids on the ATPase activity of the purified ATP8A1‐CDC50A complex. The ATPase activity was measured in the presence of 5 mM ATP and 10 mol % of one of the following lipids: 1,2‐dioleoyl‐phosphatidycholine (PC), 1,2‐dioleoyl‐PS, 1,2‐dioleoyl‐PE, 1,2‐dioleoyl‐phosphatidylglycerol (PG), 1,2‐dioleoyl‐phosphatidylinositol (PI), 1,2‐dioleoyl‐phosphatidic acid (PA), sphingomyelin (SM), cholesterol (Chol), or brain polar lipid (BPL) and 90% PC. The activity of the ATP8A1 (E191Q)‐CDC50A in the presence of 1,2‐dioleoyl‐PS was also determined.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "B NBD‐labeled PS or PE transport (flippase) activity of ATP8A1 (WT and E191Q)‐CDC50A complex. The percentage of NBD‐lipid flipped was shown.",
    "ncbi_link": "ATP8A1: 10396"
  },
  {
    "caption": "F-H COS‐1 cells stably expressing GFP‐lact‐C2 were treated with ATP8A1 siRNA1 or EHD1 siRNA1 for 72 h and stained with recombinant 2xPH and anti‐GM130 antibody. The intensities of 2xPH staining and GFP‐lact‐C2 in RE area were measured. The intensity of 2xPH (G) and the ratio of 2xPH to GFP‐lact‐C2 intensities (H) are shown. In (H), data are normalized to that of control cells. Data represent mean ± SD and were analyzed with two‐tailed Student's t‐test (n > 26 cells from three independent experiments). **P 0.01; ***P 0.001; NS, not significant. Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396
EHD1: 10938"
  },
  {
    "caption": "D Cells were treated with ATP8A1 siRNA1 for 72 h. ATP8A2‐1D4 (WT or mutants) and myc‐CDC50A were transfected 48 h after siRNA transfection. The cells were then stained for EHD1 and 1D4‐tag. Scale bars, 10 μm.",
    "ncbi_link": "ATP8A1: 10396
ATP8A2: 51761"
  },
  {
    "caption": "F Cells were treated with ATP8A1 siRNA for 72 h. GFP‐ATP8A2 (WT or mutant) and myc‐CDC50A were transfected 48 h after siRNA transfection. The cells were then stained for TfnR. Data represent mean ± SD of three or four independent experiments. At least 20 cells were counted per experiment.",
    "ncbi_link": "ATP8A1: 10396
ATP8A2: 51761"
  },
  {
    "caption": "G, H Surface biotinylation assay with Atp8a2+/+ or Atp8a2−/− cortical neurons. The ratio of surface to total TfnR was quantified and normalized to Atp8a2+/+. Data represent mean value (2 mice for each genotype).",
    "ncbi_link": "Atp8a2: 50769"
  },
  {
    "caption": "A, miR-203 expression, as determined by qPCR, in five temporal different stages of normal early development: oocyte, 2-cell embryo, morula, compacted morula and blastocyst. RNA was extracted from 30 different embryos and pooled in two independent groups for analysis by qPCR. RNA expression is normalized by a housekeeping miRNA (miR-16) that maintained invariable during early embryogenesis. Data represent the mean of 6 different qPCR measures (red bars). P=0.05 (Student's t-test) comparing 2C/morula versus compacted morula/blastocyst.",
    "ncbi_link": "miR-16: 
miR-203: 387199"
  },
  {
    "caption": "H, Representative images of EBs derived from human iPSCs transiently transfected with either control (left) or miR-203 mimics (right), at different time points during the differentiation process. Scale bars, 500 μm. I, Left panel shows the quantification of EBs size derived from human iPSCs transiently transfected with either control or miR-203 mimics as in panel (H) at different time points during the differentiation process. The percentage of EBs presenting internal large cavities during the indicated time course of differentiation is shown in the right panel. Data are mean ± s.e.m. (n=3 independent experiments). ***P<0.001 (Student´s t-test). ",
    "ncbi_link": "miR-203: 406986"
  },
  {
    "caption": "B, C, Relative Luciferase Units (RLU; normalized to Renilla luciferase and relative to DNA amount) in 293T cells transfected with DNA constructs carrying the wild-type 3´UTRs from the indicated transcripts (B) or the mutated versions of Dnmt3a and Dnmt3b 3´UTRs, downstream of the luciferase reporter (C). Cells were co-transfected with Renilla luciferase as a control of transfection, and a plasmid expressing GFP or miR-203-GFP. Data are represented as mean ± s.d. (n=3 independent experiments).",
    "ncbi_link": "GFP: 
GFP.: 
Luciferase: 
luciferase: 
Dnmt3a: 13435
Dnmt3b: 13436
miR-203: 406986"
  },
  {
    "caption": "E, Representative images of embryoid bodies (EBs) derived from wild-type iPSCs in which the expression of Dnmt3a and Dnmt3b was transiently repressed by siRNAs. Scale bars, 500 μm. Plots show the quantification of the size of EBs and the percentage of EBs with large cavities or beating at different time points during the differentiation process. Data are represented as mean ± s.e.m. (n=3 independent experiments).",
    "ncbi_link": "Dnmt3a: 13435
Dnmt3b: 13436"
  },
  {
    "caption": "F, Expression levels of Dnmt3a or Dnmt3b transcripts after transfection of wild-type iPSCs with specific siRNAs either against Dnmt3a, Dnmt3b or a combination of both (Dnmt3a/b) (as indicated in E). RNA expression was measured 24 hours after the transfection protocols and was normalized by GAPDH mRNA levels. Data are represented as mean ± s.e.m. (n=3 independent experiments).",
    "ncbi_link": "GAPDH: 
Dnmt3a: 13435
Dnmt3b: 13436"
  },
  {
    "caption": "G, Representative images of EBs derived from miiPSCs that were transiently and simultaneously transduced with Dnmt3a and Dnmt3b cDNAs or empty vectors, and simultaneously treated with Dox to induce miR-203 expression. Scale bars, 500 μm. Plots show the quantification of EB size, percentage of EBs with large cavities, and beating EBs at different time points during differentiation. Data are represented as mean ± s.e.m. (n=3 independent experiments).",
    "ncbi_link": "Dnmt3a: 13435
Dnmt3b: 13436
miR-203: 406986"
  },
  {
    "caption": "H, Expression levels of miR-203, Dnmt3a or Dnmt3b transcripts in iPSCs after induction of miR-203 (miiPSCs) and transduced with Dnmt3a and Dnmt3b cDNAs or empty vectors (as indicated in G). RNA expression was measured 24 hours after the transfection protocols and was normalized by a control miRNA (miR-142) or GAPDH mRNA, respectively. Data are represented as mean ± s.e.m. (n=3 independent experiments).",
    "ncbi_link": "GAPDH: 
miR-142: 
Dnmt3a: 13435
Dnmt3b: 13436
miR-203: 406986"
  },
  {
    "caption": "H, The specific differentially methylated regions (DMR) at the Sirt6 locus were analyzed by PCR amplification and sequencing of bisulphite-modified DNA. Ten independent clones were sequenced per condition. The quantification of methylated (filled circles) vs. unmethylated (empty circles) CpGs is shown in the histogram in the indicated conditions.",
    "ncbi_link": "Sirt6: 50721"
  },
  {
    "caption": "B, Representative immunofluorescences showing cardiac Troponin T (cTnT, green) and nuclei (Hoechst, blue) staining of in vitro-generated cardiomyocytes derived from wild-type iPSCs transiently transfected with either control mimics, miR-203 mimics or miR-203 mimics + Dnmt3a/b cDNAs. Pictures were taken at day 15 of differentiation. Scale bars, 68 μm. The cTnT-positive area in these cardiomyocytes is shown in the right histogram. Data are represented as mean ± s.d. (n=2 independent experiments with 6 replicates each).",
    "ncbi_link": "Dnmt3a: 13435
miR-203: 406986"
  },
  {
    "caption": "Western blot showing STN1 knockdown. shLUC (siRNA targeting luciferase) was used as the control.",
    "ncbi_link": "LUC: 
luciferase: 
STN1: 79991"
  },
  {
    "caption": "CST deficiency causes ssDNA accumulation upon fork stalling. HeLa cells with STN1 knockdown were incubated with 10 µM BrdU for 48 h, followed by 2 mM HU treatment for 3 h, and subsequently stained with BrdU antibody under a non-denaturing condition to detect ssDNA. N, the number of cells analyzed in each condition. Relative BrdU fluorescence intensity was quantitated by Image J.",
    "ncbi_link": "STN1: 79991"
  },
  {
    "caption": "DNA fiber analysis of U2OS cells with STN1 knockdown and its RNAi-resistant Flag-STN1 WT re-expression with and without mirin treatment.",
    "ncbi_link": "Flag: 
STN1: 79991"
  },
  {
    "caption": "DNA fiber analysis of BJ cells with STN1 knockdown by two siRNA sequence with and without mirin treatment.",
    "ncbi_link": "STN1: 79991"
  },
  {
    "caption": "DNA fiber analysis of HCT116 cells with STN1 knockdown with and without mirin treatment.",
    "ncbi_link": "STN1: 79991"
  },
  {
    "caption": "DNA fiber analysis of U2OS cells showing that SMARCAL1-mediated fork reversal is needed for nascent-stand degradation observed in CST-deficient cells.",
    "ncbi_link": "SMARCAL1: 50485"
  },
  {
    "caption": "DNA fiber analysis of U2OS cells showing that ZRANB3-mediated fork reversal is needed for nascent-strand degradation observed in CST-deficient cells.",
    "ncbi_link": "ZRANB3: 84083"
  },
  {
    "caption": "SIRF detection of MRE11 at stalled forks in STN1-deficient U2OS cells. Representative SIRF images of MRE11 at normal or stalled replication forks are shown. Scale bars: 10 µm.",
    "ncbi_link": "STN1: 79991"
  },
  {
    "caption": "ssDNA accumulation analysis in STN1-deficient U2OS cells with and without mirin treatment. Representative images of native BrdU staining are shown.",
    "ncbi_link": "STN1: 79991"
  },
  {
    "caption": "Coomassie blue stained SDS-PAGE gel (15%) of purified human CST complex (CTC1 wild- type and ∆700N).",
    "ncbi_link": "CTC1: 80169"
  },
  {
    "caption": "Deletion of the N-terminal 700 aa of CTC1 abolishes CTC1 localization at telomeres. U2OS stably expressing vector (V), WT Myc-CTC1 and Myc-∆700N were treated with or without HU and co-stained with Myc (red) and TRF2 (green) antibodies. Boxed areas are amplified in inserts to indicate CTC1/TRF2 colocalization (yellow).Scale bars: 10 μm. Quantification of percent of cells with >3 CTC1/TRF2 colocalization foci were from three independent experiments. In each experiment, >150 cells from each sample were analyzed.",
    "ncbi_link": "Myc: 
CTC1: 80169"
  },
  {
    "caption": "   ∆700N does not affect CST complex formation. HEK293T cells were co-transfected with Myc- CTC1 or Myc-∆700N, His6-STN1 and HA-TEN1. Co-IP was performed with Myc antibody to pulldown His6- STN1 and HA-TEN1. Full-length Myc-CTC1 was prone to degradation during immunoprecipitation.   ",
    "ncbi_link": "HA: 
His: 
Myc: 
STN1: 79991
CTC1: 80169
TEN1: 100134934"
  },
  {
    "caption": "   ∆700N retains RAD51 interaction. HEK293T cells were co-transfected with Myc-CTC1 or Myc-∆700N, His6- STN1, HA-TEN1 and Flag-RAD51 or vector control (V), and treated with HU (2 mM, 16 h). Co-IP was performed with Flag antibody to pulldown Myc-CTC1.   ",
    "ncbi_link": "Flag: 
HA: 
His: 
Myc: 
STN1: 79991
CTC1: 80169
RAD51: 5888
TEN1: 100134934"
  },
  {
    "caption": "DNA fiber analysis of CTC1 depleted U2OS cells with RNAi-resistant WT or ∆700N re-expression. Mean values in each sample are listed at the top of the graph. N, the number of cells analyzed in each condition, ***",
    "ncbi_link": "CTC1: 80169"
  },
  {
    "caption": "Micronuclei (MN) formation in BRCA2- and STN1-deficient cells. Co-depletion was achieved by transfecting siBRCA2 in U2OS cells expressing shSTN1. Representative DAPI staining images are shown. Arrows point to MN. Scale bars: 20 µm. Average percentages of nuclei containing MN from three independent experiments are presented. In each experiment, >300 nuclei were analyzed per sample.",
    "ncbi_link": "BRCA2: 675
STN1: 79991"
  },
  {
    "caption": "Anaphase bridges (arrows) in BRCA2- and STN1-deficient U2OS cells. Scale bar: 10 µm. Average percentages of anaphase bridges from three independent experiments are presented.",
    "ncbi_link": "BRCA2: 675
STN1: 79991"
  },
  {
    "caption": "   γH2AX induced by BRCA2 knockdown and STN1 knockdown in U2OS cells. Nuclei containing ≥ 5 foci were considered as positive γ-H2AX staining. Results were from three independent knockdown experiments. In each experiment, >80 cells were analyzed per sample.   ",
    "ncbi_link": "BRCA2: 675
STN1: 79991"
  },
  {
    "caption": "Co-depletion of STN1 and BRCA2 significantly impairs DNA replication. Scale bar: 50 µm. Results were from three independent knockdown experiments. In each experiment, >180 nuclei were analyzed per sample.",
    "ncbi_link": "BRCA2: 675
STN1: 79991"
  },
  {
    "caption": "Co-depletion of STN1 and BRCA2 increases chromosome instabilities. U2OS cells with siBRCA2 and/or shSTN1 knockdown were treated with HU (2 mM, 3 h). Representative metaphase images show aberrant chromosomes (red arrows). Boxed areas are amplified and shown at the bottom of images. Scale bars: 20 µm. Two independent knockdown and chromosome spread experiments were performed. N, the number of metaphase spreads analyzed in each sample.",
    "ncbi_link": "BRCA2: 675
STN1: 79991"
  },
  {
    "caption": "RAD51 foci formation in U2OS CTC1 knockdown cells was rescued by RNAi-resistant WT but not by ∆700N. Cells were treated with HU (2 mM, 16 h) and stained with anti-RAD51. Representative images are shown. Scale bars: 10 µm. Scatter plot of RAD51 foci number with and without HU treatment is shown. Mean values in each condition are listed at the top of the graph.",
    "ncbi_link": "CTC1: 80169"
  },
  {
    "caption": "DNA fiber analysis of nascent-strand DNA degradation in U2OS cells with STN1 and RAD51 co-depletion. Three independent treatments were performed and results from one biological replicate are shown. N, the number of DNA fibers analyzed in each sample in one experiment. Western blots showing protein knockdown in DNA fiber assays are included.",
    "ncbi_link": "RAD51: 5888
STN1: 79991"
  },
  {
    "caption": "A. Raw 264.7 macrophage cells were treated with DMSO (0.05%), 1 μM control antisense oligonucleotide (ASO), or Rab10-directed ASO (1 μM), for four days. Immunoblots are representative of three independent experiments, with similar results obtained. B. Calculated reduction of Rab10 (n=3 biologically independent experiments). Each dot in the plot presents one independent experiment. Group are shown. Error bars represent ± SEM. Significance was assessed by one-way ANOVA with Tukey's post hoc test, with **** representing P <0.0001.",
    "ncbi_link": "Rab10: 19325"
  },
  {
    "caption": "A. Raw 264.7 macrophage cells were transfected with FLAG(N-term)-Rab10 and eGFP(C-term)-Akt-PH domain (PI(3,4,5)P3 marker), or eGFP(C-term)-SARA-Fyve domain (PI3P marker), or eGFP(C-term)-PLC-PH domain (PI(4,5)P2 marker), or mkate2(N-term)-2xTAPP1-PH domain (PI(3,4)P2 marker). Representative photomicrographs (from 25 images analyzed for each condition from n=3 biologically independent experiments) are shown from fixed cells immuno-stained for FLAG-tag (Rab10, shown as green) together with eGFP epifluorescence (shown as red). White bounding boxes show \"High Mag\" panels that magnify representative individual vesicles. The colocalization of Rab10 and indicated markers in the bounding boxes were analyzed using Image J as described in the method and shown in the \"CoLoc\" panels. The colocalized pixels are shown in white with the same intensity. Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panels and \"CoLoc\" panels. White arrow heads indicate representative Rab10 vesicles positively colocalized with the indicated marker. B. At least 25 cells across three independent experiments were analyzed for each condition (see Materials and Methods section). % of Rab10 vesicles positive with the indicated marker within each cell was quantified. Each dot represents the mean value from one cell analyzed. Group means are given, with error bars representing ± SEM. ",
    "ncbi_link": "eGFP: 
FLAG: 
mkate2: 
Akt: 11651
PLC: 5333
TAPP1: 59338
Rab10: 10890
SARA: 51128"
  },
  {
    "caption": "C. Raw 264.7 macrophage cells were transfected with FLAG(N-term)-Rab10 and eGFP(C-term)-Akt-PH domain (PI(3,4,5)P3 marker) and treated with wortmannin (1 μM) for one hour. Representative photomicrographs (from 25 cells analyzed for each condition from n=3 biologically independent experiments) are shown from fixed cells immuno-stained for FLAG-tag (Rab10, shown as green) together with eGFP epifluorescence (shown as red). Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panel. D. Percent of cells treated with or without wortmannin harboring Rab10 vesicles was calculated from >30 cells across five independent experiments. Each dot on the plot represents mean values from one experiment. Error bars represent ± SEM and significance was assessed by Mann-Whitney test (owing to non-normal distributions) with ** indicating P<0.01. ",
    "ncbi_link": "eGFP: 
FLAG: 
Akt: 11651
Rab10: 10890"
  },
  {
    "caption": "E. Raw 264.7 cells were co-transfected with eGFP(N-term)-Rab10 and mRuby(N-term)-Rab5 for 48 hours, with live-cell recordings for ~10 minutes. A representative vesicle is shown over the presented time-lapse. Scale bar represents 1 μm. F. Fluorescence intensities of individual vesicles are calculated over time. Dots show mean values calculated from n=8 recorded vesicles from cells from n=3 biologically independent experiments. Error bars show ± SEM. ",
    "ncbi_link": "eGFP: 
mRuby: 
Rab10: 10890
Rab5: 5868"
  },
  {
    "caption": "Raw264.7 cells were transfected with plasmids expressing eGFP(N-term)-WT-Rab10 or Q68L-Rab10 (GTP-locked). 24-hours later, cells were incubated with (A) TRITC-dextran (70 kDa, shown as red signal) Representative photomicrographs are from 25 cells each analyzed for each condition from n=3 biologically independent experiments. White bounding boxes are magnified in \"High Mag\" panels that show individual vesicles. Positive co-localization signal (see Methods) is indicated in bounding boxes labeled as \"CoLoc.\" Colocalized pixels are shown in white. Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panels and \"CoLoc\" panels. White arrow heads indicate Rab10 vesicles colocalized with the indicated marker.",
    "ncbi_link": "eGFP: 
Rab10: 10890"
  },
  {
    "caption": "Raw264.7 cells were transfected with plasmids expressing eGFP(N-term)-WT-Rab10 or Q68L-Rab10 (GTP-locked). 24-hours later, cells were incubated with (B) DQ-ovalbumin, for 30 min before washing and fixation. Representative photomicrographs are from 25 cells each analyzed for each condition from n=3 biologically independent experiments. White bounding boxes are magnified in \"High Mag\" panels that show individual vesicles. Positive co-localization signal (see Methods) is indicated in bounding boxes labeled as \"CoLoc.\" Colocalized pixels are shown in white. Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panels and \"CoLoc\" panels. White arrow heads indicate Rab10 vesicles colocalized with the indicated marker.",
    "ncbi_link": "eGFP: 
Rab10: 10890"
  },
  {
    "caption": "Raw264.7 cells were transfected with plasmids expressing eGFP(N-term)-WT-Rab10 or Q68L-Rab10 (GTP-locked). (C, D) Cells were further stained for (C) EEA1, or (D) Lamp1, which was detected with Cy5 dye (show as red signal). Representative photomicrographs are from 25 cells each analyzed for each condition from n=3 biologically independent experiments. White bounding boxes are magnified in \"High Mag\" panels that show individual vesicles. Positive co-localization signal (see Methods) is indicated in bounding boxes labeled as \"CoLoc.\" Colocalized pixels are shown in white. Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panels and \"CoLoc\" panels. White arrow heads indicate Rab10 vesicles colocalized with the indicated marker.",
    "ncbi_link": "eGFP: 
Rab10: 10890"
  },
  {
    "caption": "A. Raw 264.7 macrophage cells were transfected with Flag(N-term)-Rab10 and eGFP(C-term)-Akt-PH domain(PI(3,4,5)P3 marker), or eGFP(C-term)-SARA-Fyve domain((PI3P marker), or eGFP(C-term)-PLC-PH domain (PI(4,5)P2 marker, epifluorescence, shown in blue) followed by anti-Flag immunofluorescence (shown in green) and pT73-Rab10 antibody (shown in red). To evaluate colocalization of phospho-Rab10 with early endosomes or late endosome/lysosome markers, immunofluorescence detection was performed for endogenous EEA1 or Lamp1 (shown in blue). Raw 264.7 macrophage cells were further fed 0.05 mg mL-1 of 70 kDa TRITC-conjugated dextran (epifluorescence, shown in blue) or 0.05 mg mL-1 BODIPY conjugated ovalbumin for 30min prior to immunofluorescence analysis. Representative images were selected from 25 cells analyzed for each condition from n=3 biologically independent experiments. White bounding boxes are \"High Mag\" panels that show individual vesicles analyzed. Scale bars represent 10 μm and 1 μm for \"High Mag\". Positive colocalization signal (depicted as white) in the \"CoLoc (pRab10/Rab10)' and 'CoLoc (pRab10/Marker)' columns are indicated. White arrow heads highlight vesicles scored as co-positive between pT73-Rab10 and Rab10 or the indicated marker. B. 25 cells across three independent experiments were analyzed for each condition, with each dot representing the mean of the vesicle analysis across individual cells. The group means of %pT73-Rab10 vesicles positive for the indicated marker are given, with error bars showing ± SEM. ",
    "ncbi_link": "eGFP: 
Flag: 
Akt: 11651
PLC: 5333
Rab10: 10890
SARA: 51128"
  },
  {
    "caption": "A. Raw264.7 cells were transfected with Flag(N-term)-LRRK2 and eGFP(N-term)-Rab10 for 24 hours and treated with or without the LRRK2 kinase inhibitor MLi2 (100 nM) for two hours. Representative photomicrographs (from >20 images analyzed for each condition from n=3 biologically independent experiments) are shown from fixed cells with eGFP(N-term)-Rab10 epifluorescence (shown as green signal), and immuno-stained for pT73-Rab10 (shown as red signal) and LRRK2 (shown as blue signal). White bounding boxes are magnified in \"High Mag\" panels that show individual vesicles. Scale bars represent 10 μm or 1 μm in \"Hig Mag\" panels.",
    "ncbi_link": "eGFP: 
Flag: 
LRRK2: 120892
Rab10: 10890"
  },
  {
    "caption": "B. Raw 264.7 macrophage cells transfected with eGFP(N-term)-Rab10 and Flag(N-term)-LRRK2 were sequentially lysed mechanically into buffer to create a 'soluble' protein fraction, and then insoluble material lysed into triton X-100 buffer to create a \"triton x-100\" fraction. The \"soluble\" and triton X-100 buffer solubilized fractions were analyzed using SDS-PAGE (TGX gels), and representative immunoblots from n=3 independent experiments are shown.",
    "ncbi_link": "eGFP: 
Flag: 
LRRK2: 120892
Rab10: 10890"
  },
  {
    "caption": "A,B. Primary mouse bone marrow-derived macrophage cells (BMDM) from adult male WT-LRRK2 mBAC transgenic mice were pre-incubated with FITC-conjugated dextran (70 kDa, green signal) prior to washing, fixing, and immunostaining with total-Rab10 (shown as red signal), or pT73-Rab10 antibody (shown as red signal). Alternatively, cells were co-stained with antibodies to Rab5, Rab7 or Lamp1 (shown as green signal in separate images). Representative photomicrographs (from >30 images analyzed for each condition from n=3 biologically independent experiments) are shown. White bounding boxes are \"High Mag\" panels that show individual vesicles analyzed. Positive colocalization signal (depicted as white) in \"CoLoc\" panels are given with white arrow heads highlighting vesicles scored as co-positive between pT73-Rab10 and the indicated marker. Scale bars are 10 μm, or 1 μm in \"Hig Mag\" panels and \"CoLoc\" panels.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "D. Primary mouse bone marrow-derived macrophage cells (BMDM) from adult male WT-LRRK2 mBAC transgenic mice were treated with 0.001% DMSO or 100 nM MLi2 (i.e., IC90 concentration) for two hours prior to immunostaining with total Rab10 or pT73-Rab10 antibody (shown as red signal), and anti-Rab5 or anti-Rab7antibody (shown as green signal). Representative photomicrographs (from 20 cells analyzed for each condition from n=3 biologically independent experiments) are shown. White bounding boxes are \"High Mag\" panels that show individual vesicles analyzed. Scale bars represent 10 μm and 1 μm for \"High Mag\". Positive colocalization signal (depicted as white) in \"CoLoc\" panels are given with white arrow heads highlighting vesicles scored as co-positive between pT73-Rab10 and the indicated marker.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "F. Raw 264.7 macrophage cells were transfected with eGFP(N-term)-Rab10 for 24 hours and treated with or without the LRRK2 kinase inhibitor MLi2 (100 nM) for two hours. Representative photomicrographs (from 25 images analyzed for each condition across n=3 biologically independent experiments) are shown with eGFP(N-term)-Rab10 epifluorescence (shown as green signal) and pT73-Rab10 (shown as red signal), with EEA1 (shown as blue signal). White bounding boxes are \"High Mag\" panels that show individual vesicles analyzed. Scale bars represent 10 μm and 1 μm for \"High Mag\". Positive colocalization signal (depicted as white) in \"CoLoc\" panels are given with white arrow heads highlighting vesicles scored as co-positive between pT73-Rab10 Rab10 and the indicated marker. G. Calculated percentage of colocalized vesicles, with each dot representing mean vesicle frequency in each cell analyzed. The group mean of % Rab10 vesicles positive with EEA1 were calculated, and error bars represent ± SEM. Significance was assessed by Mann-Whitney test for each marker with *** representing P<0.005. ",
    "ncbi_link": "eGFP: 
Rab10: 10890"
  },
  {
    "caption": "A. Raw264.7 cells were transfected with Flag-Rab10 or control empty vector. The transfected cells were lysed in the presence of 2 mM GTPγS or 2 mM GDP. The Flag-Rab10 complex was immunoprecipitated with Flag-resin followed by extensive washing and elution of complexes with 200 μg mL-1 3xFlag-tide. Eluates were analyzed by SDS-PAGE followed by immuno-blotting with anti-Flag-HRP antibody.",
    "ncbi_link": "Flag: 
Rab10: 10890"
  },
  {
    "caption": "C. Flag(N-term)-Rab10 protein was purified from HEK293-FT cells transfected with Flag(N-term)-Rab10 plasmids and immobilized on Flag-resin in lysis buffer containing 2 mM GTPγS, or 2 mM GDP, as indicated. Beads were mixed with lysates from cells transfected with Myc-mkate2(N-term)-EHBP1L1 to generate Rab10:EHBP1L1 complexes. Total Rab10 on the beads was detected using anti-Flag antibody, and EHBP1L1 immobilized to total Rab10 detected with an anti-Myc antibody. Representative immunoblots from n=3 biologically independent experiments are shown. D. Quantification of relative EHBP1L1 pulled down. Data are from n=3 biologically independent experiments. Error bars represent ± SEM... ",
    "ncbi_link": "Flag: 
mkate2: 
Myc: 
EHBP1L1: 254102
Rab10: 10890"
  },
  {
    "caption": "E. HEK293-FT cells were transfected with Flag(N-term)-Rab10 and Myc(N-term)-LRRK2R1441C to induce Rab10 phosphorylation. Membrane bound Flag(N-term)-Rab10 protein was extracted with Flag-resin to generate 'pRab10 beads,' or extracted from cells treated with MLi2 (100 nM) to generate 'Rab10 beads.' Beads were mixed with lysates from HEK293-FT cells transfected with Myc-mkate2(N-term)-EHBP1L1 to form on-bead Rab10:EHBP1L1 complexes. The total Rab10 and pT73-Rab10 on the beads was detected using anti-Flag antibody and pT73-Rab10 antibody. The EHBP1L1 in the lysates and immobilized on the beads was detected using anti-Myc tag antibody. Representative immunoblots are shown. F. The relative EHBP1L1 pulled down, normalized to total Rab10 protein on-bead, was determined from n=3 biologically independent experiments. Error bars represent ± SEM. Each dot represents one experiment, with significance assessed by one-way ANOVA with **** representing Tukey's post hoc test P<0.0001. ",
    "ncbi_link": "Flag: 
mkate2: 
Myc: 
EHBP1L1: 254102
LRRK2: 120892
Rab10: 10890"
  },
  {
    "caption": "G. Raw 264.7 cells were co-transfected with eGFP(N-term)-Rab10 (epifluorescence shown in green) and Myc-mkate2(N-term)-EHBP1L1 (epifluorescence shown in blue), or Flag(C-term)-RILPL2 (anti-Flag signal shown in blue). Cells were stained for pT73-Rab10 (shown in red). Representative photomicrographs of individual vesicles (from >10 cells analyzed for each condition from n=3 biologically independent experiments) are shown. Scale bar represents 1 μm. H. Pearson's colocalization coefficient for Rab10 and pT73-Rab10, EHBP1L1 and RILPL2 on vesicle bodies and tubular vesicles. Data are from n=20 vesicles with tubular structures positive for pT73-Rab10, and n=12 vesicles with tubular structures positive for EHBP1L1, or RILPL2, calculated from cells from three independent experiments. Each dot represents one vesicle body or tubular structure, with significance assessed by Kruskal-Wallis test followed by Dunn's multiple comparison test with *** representing P<0.0005 and **** P<0.0001. Error bars represent ± SEM.. ",
    "ncbi_link": "eGFP: 
Flag: 
mkate2: 
Myc: 
EHBP1L1: 254102
Rab10: 10890
RILPL2: 196383"
  },
  {
    "caption": "I. Raw264.7 cells were co-transfected with Flag(N-term)-Rab10, Flag(N-term)-LRRK2R1441C, and Myc(N-term)-EHBP1L1, with representative immunoblots shown. J. Relative pT73-Rab10 levels were calculated as fold of cells transfected with Flag(N-term)-Rab10 and Flag(N-term)-LRRK2 only. Data are from n=3 biologically independent experiments. Each dot represents one independent experiment. Significance was assessed by one-way ANOVA with **** representing Tukey's post hoc test P<0.0001.",
    "ncbi_link": "Flag: 
Myc: 
EHBP1L1: 254102
LRRK2: 120892
Rab10: 10890"
  },
  {
    "caption": "K. Raw264.7 cells were co-transfected with eGFP(N-term)-Rab10 (epifluorescence, shown in green) and Myc-mkate2(N-term)-EHBP1L1 or Myc-mkate2 control plasmid (epifluorescence, shown in red). Representative photomicrographs are shown. Bounding boxes highlight vesicles in \"High Mag\" panels. Scale bars represent 10 μm, and 1 μm for \"High Mag\" images. L. % of eGFP(N-term)-Rab10 vesicles positive with pT73-Rab10 were calculated (from 25 cells analyzed for each condition from n=3 biologically independent experiments). Each dot represents the mean frequency observed in one cell. Error bars show ± SEM with significance was assessed by Mann-Whitney test. *** represents P<0.0005. ",
    "ncbi_link": "eGFP: 
mkate2: 
Myc: 
EHBP1L1: 254102
Rab10: 10890"
  },
  {
    "caption": "A-D. Primary mouse bone marrow-derived macrophage cells (BMDM) from adult male WT-mLRRK2 BAC transgenic mice were immunostained with anti-mouse CCR5, or CD11b, or MHC II antibody (shown as green signal) and (A) total Rab10 antibody (red signal), or (B) pT73-Rab10 antibody (red signal) as indicated. Representative photomicrographs (from >20 images analyzed for each condition from n=3 biologically independent experiments) are shown. (C) Photomicrographs showing the different cargo with respect to Rab10 tubular structures. (D) EEA1 (shown as green signal) with total Rab10 or pT73-Rab10 (shown as red signals) as indicated. Bounding boxes in panels A-D are magnified in \"High Mag\" panels that show individual vesicles. Scale bars represent 10 μm and 2 μm for \"High Mag\" images.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "A. Primary mouse bone marrow-derived macrophage cells (BMDM) from adult male WT-mLRRK2 BAC transgenic mice were treated with DMSO, 1 μM Rab10 anti-sense oligonucleotide for 4 days, 100 nM MLi2 for 12 hours, as indicated, before stimulation with 100 nM CCL5 for the indicated time (hours). Representative immunoblots from n=3 biologically independent experiments are shown. B. Relative pSer473-Akt levels were normalized to total Akt and calculated as fold of naïve cells (without CCL5 stimulation). Data shown are group means ± SEM from n=3 biologically independent replicates, with significance assessed by one-way ANOVA with Tukey's post hoc test with treated groups compared to matched control groups, with ** representing P< 0.01. ",
    "ncbi_link": "LRRK2: 66725
Rab10: 19325"
  },
  {
    "caption": "(A) smFISH targeting Bmal1, Cry1 and Nr1d1 in wild-type NIH 3T3 cells at 17h, 29h and 25h after synchronisation with Dex, respectively. Nuclei are stained with DAPI (blue). Each fluorescent dot (white) corresponds to a single transcript. Segmented cell boundaries are delineated in grey. The blue and white channels represent maximum z-projections. Scale bar: 20μm.",
    "ncbi_link": "Bmal1: 11865
Cry1: 12952
Nr1d1: 217166"
  },
  {
    "caption": "(B) Number of Bmal1, Cry1, and Nr1d1 transcripts per cell as a function of time after treatment with Dex. These data combine all smFISH hybridizations from the 4h sampled Nr1d1/Cry1 and Bmal1/Cry1 experiment. Each dot shows the average over one replicate from an independent slide (Methods). The solid lines represent fits using a two-harmonic cosinor model (Equation (1), Methods) for each gene individually.",
    "ncbi_link": "Bmal1: 11865
Cry1: 12952
Nr1d1: 217166"
  },
  {
    "caption": "(D) Distributions of Nr1d1, Cry1 and Bmal1 transcripts at 21h, 29h and 37h after synchronisation with Dex. μ represents the mean of the distribution, CV represent the coefficient of variation (standard deviation / mean), and N is the number of cells at the given time point. Total number of cells analysed for the Nr1d1/Cry1 pair: 21h - 449; 25h - 414; 29h - 521; 33h - 463; 37h - 477; 41h - 429. Total number of cells analysed for the Bmal1/Cry1 pair: 17h - 465; 21h - 490; 25h - 504; 29h - 436; 33h - 407; 37h - 454; 41h - 404.",
    "ncbi_link": "Bmal1: 11865
Cry1: 12952
Nr1d1: 217166"
  },
  {
    "caption": "(B) Top image: Dual-channel smFISH targeting Bmal1 and Cry1 simultaneously, taken at 17h after Dex synchronisation. Blue, nuclei stained with DAPI; green dots, Bmal1 transcripts; red, Cry1 transcripts. Bottom image: Dual-channel smFISH targeting Nr1d1 and Cry1 simultaneously, taken at 25h after Dex synchronisation. Blue, nuclei stained with DAPI; green dots, Nr1d1 transcripts; red, Cry1 transcripts. Scale bar: 20μm.",
    "ncbi_link": "Bmal1: 11865
Cry1: 12952
Nr1d1: 217166"
  },
  {
    "caption": "(C) Bivariate distributions of mRNA counts per cell for dual-channel smFISH targeting either Bmal1 and Cry1 or Nr1d1 and Cry1. Each dot corresponds to a single cell, and the contours represent KDE estimates of the density. Time represents the number of hours after Dex synchronisation, and R represents the Pearson correlation coefficient.",
    "ncbi_link": "Bmal1: 11865
Cry1: 12952
Nr1d1: 217166"
  },
  {
    "caption": "G) Kaplan Meier survival curve for PYCR1 levels in residual cancer in the current proteomics data. Cox univariate p value, risk table and hazard ratio with 95% CI indicated.",
    "ncbi_link": "PYCR1: 5831"
  },
  {
    "caption": "F) Normalized lactate concentration upon PYCR1 KO. Data represents mean ± SE of three biological experiments. Samples are compared using Kruskal Wallis test followed by Dunnett's test for multiple pairwise comparisons. Corrected p values are indicated as follows *p < 0.05. Shapiro Wilk test was used to check data normality and Bartlett test was used to examine homogeneity of variances.",
    "ncbi_link": "PYCR1: 5831"
  },
  {
    "caption": "A) Representative pictures of transwell migration and invasion after PYCR1 knockout. Scale bar :100 μm. B) Bar plot represents mean ± SD of three biological replicates for transwell migration and invasion. Samples were compared using Kruskal Wallis test followed by Dunnett's test for multiple pairwise comparisons. Corrected p-values are reported as follows *** p < 0.001. ",
    "ncbi_link": "PYCR1: 5831"
  },
  {
    "caption": "C) Representative images of colony formation in soft agar upon PYCR1 KO. Scale bar: 100 μm.",
    "ncbi_link": "PYCR1: 5831"
  },
  {
    "caption": "D) Growth measurements of MCF7 wild type and PYCR1 KO cells over 96 hours. Data represents mean ± SE of three biological experiments. Samples were compared using paired Student's t-test.",
    "ncbi_link": "PYCR1: 5831"
  },
  {
    "caption": "I) Tumor volume measurements for 26 days in MCF7 injected NSG mice. CRISPR control and PYCR1 KO tumors with (n=8) and without treatment (n=5) are shown. Data represents mean ± SE. Pax: Paclitaxel, Dox: Doxorubicin. Groups were compared by one way ANOVA followed by Tukey's multiple comparisons test for pairwise group comparisons. Corrected p-values are reported as follows *p < 0.05, ** p < 0.01. Shapiro Wilk test was used to check data normality and Bartlett test was used to examine homogeneity of variances.",
    "ncbi_link": "CRISPR: 
PYCR1: 5831"
  },
  {
    "caption": "J) Bar plot indicates mean ± SE of tumor volume measurements for day 26. CRISPR control and PYCR1 KO tumors with (n=8) and without treatment (n=5) were compared by one way ANOVA followed by Tukey's multiple comparisons test for pairwise group comparisons. Corrected p-values are reported as follows *** p < 0.001. Shapiro Wilk test was used to check data normality and Bartlett test was used to examine homogeneity of variances.",
    "ncbi_link": "CRISPR: 
PYCR1: 5831"
  },
  {
    "caption": "(B) Cells expressing TAP-tagged Atg38 and the indicated HA-tagged proteins were grown in YPD. The extracts were prepared and were immunoprecipitated by IgG-Dynabeads as described in Materials and methods. The whole-cell extract (left, \"input\") and the precipitated proteins (right) were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Atg38: 850908"
  },
  {
    "caption": "(D) Cell extracts were prepared from wild-type and atg14Δ cells expressing Atg38-TAP as well as HA-tagged proteins of complex I components. The IgG Dynabead-precipitated proteins (bottom), together with the whole-cell extracts (top), were immunoblotted with the indicated antibodies.",
    "ncbi_link": "atg14: 852425
Atg38: 850908"
  },
  {
    "caption": "(E) ATG38-2GFP ATG17-2mCherry cells in wild-type and atg14Δ were cultured at 30°C with or without rapamycin. After 180 min, cells were analyzed by fluorescence microscopy. Bar, 5 µm.",
    "ncbi_link": "atg14: 852425"
  },
  {
    "caption": "(A) Cells expressing Pho8Δ60 were grown in YPD and shifted to SD(-N) medium for 3 h at 30°C. Lysates from each group of cells were tested for ALP activity. ALP activity is shown as mean ± SD of three independent experiments with the activity of wild-type cells normalized to 1.",
    "ncbi_link": "Pho8: 852092"
  },
  {
    "caption": "(A) Wild-type and atg38Δ cells expressing the indicated GFP fusion proteins and Ape1-mRFP were cultured at 30°C in the presence of rapamycin. After 60 min, cells were analyzed by fluorescence microscopy. Of the total pool of Ape1-mRFP signal, the percentage of Ape1-mRFP colocalizing with GFP was calculated. This percentage is shown as mean ± SD of two independent experiments, with the number of cells counted indicated at the bottom of the graph. (B) Examples of wild-type and atg38Δ cells expressing either Atg14-3 × GFP or Vps34-3 × GFP in A. Bar, 5 µm.",
    "ncbi_link": "atg38: 850908"
  },
  {
    "caption": "(A) Cell extracts were prepared from wild-type and atg38Δ strains expressing TAP-tagged Atg38 and the indicated HA proteins. The extracts were immunoprecipitated by IgG-Dynabeads. The whole-cell extracts (top, \"input\") and the precipitates (bottom) were analyzed by immunoblotting with the indicated antibodies. Relative binding efficiency was determined as described in Materials and methods. To compare results from multiple experiments, the value for the reference sample (wild-type cells) was normalized to 1.0. Relative binding efficiency is shown as mean ± SD of three independent experiments.",
    "ncbi_link": "atg38: 850908
Atg38: 850908"
  },
  {
    "caption": "(C) Cells expressing Pho8Δ60 were grown in YPD and shifted to SD(-N) medium for 3 h at 30°C. Cell lysates from each group of cells were tested for ALP activity. ALP activity is shown as mean ± SD of three independent experiments with the activity of wild-type cells normalized to 1.",
    "ncbi_link": "Pho8: 852092"
  },
  {
    "caption": "(A) AH109 cells containing the indicated GAL4 activation domain fusions (bait) and GAL4 DNA-binding domain fusions (prey) were selected on SD-Leu-Trp plates at 30°C (−LW, left). The interaction of fusion proteins was examined by plating cells on SD-Leu-Trp-His (−LWH, middle) and SD-Leu-Trp-Ade (−LWA, right) plates at 30°C for 3 d.",
    "ncbi_link": "GAL4: "
  },
  {
    "caption": "(B) Interactions between the indicated fusion proteins were analyzed as in A. AH109 cells containing the indicated GAL4 activation domain fusions (bait) and GAL4 DNA-binding domain fusions (prey) were selected on SD-Leu-Trp plates at 30°C (−LW, left). The interaction of fusion proteins was examined by plating cells on SD-Leu-Trp-His (−LWH, middle) and SD-Leu-Trp-Ade (−LWA, right) plates at 30°C for 3 d.",
    "ncbi_link": "GAL4: "
  },
  {
    "caption": "(C) The TAP-tagged Vps34 protein complex was purified from the vps30Δ atg14Δ vps38Δ cells. The purified proteins were separated on SDS-PAGE and visualized by Coomassie staining. Recombinant GST-Atg38 (WT), GST-Atg381-120 (N), and GST-Atg38121-226 (C) were incubated with Vps15-Vps34-TAP complex bound to IgG-Dynabeads. The eluted proteins were analyzed by immunoblotting.",
    "ncbi_link": "atg14: 852425
Atg38: 850908
vps30: 855983
vps38: 851074"
  },
  {
    "caption": "(A) Interactions between the indicated fusion proteins were analyzed as in Fig. 4 A. AH109cells containing the indicated GAL4 activation domain fusions (bait) and GAL4 DNA-binding domain fusions (prey) were selected on SD-Leu-Trp plates at 30°C (−LW, left). The interaction of fusion proteins was examined by plating cells on SD-Leu-Trp-His (−LWH, middle) and SD-Leu-Trp-Ade (−LWA, right) plates at 30°C for 3 d.",
    "ncbi_link": "GAL4: "
  },
  {
    "caption": "(B) Analysis of Atg38 by gel filtration. Recombinant Atg38 protein was fractionated over a gel filtration column. Each fraction was subjected to SDS-PAGE and visualized by Coomassie staining.",
    "ncbi_link": "Atg38: 850908"
  },
  {
    "caption": "(A) Cell extracts were prepared from atg38Δ strains expressing Atg14-TAP and either Vps34-6HA or Vps15-6HA with Atg381-120 fused with GFP and either GBP or GBP3A. The cell extracts were immunoprecipitated with IgG-Dynabeads. The precipitated proteins, together with the whole-cell extracts, were immunoblotted with the indicated antibodies (left). Relative binding efficiency was determined as described in Fig. 3 A and was shown as mean ± SD of three independent experiments.",
    "ncbi_link": "atg38: 850908"
  },
  {
    "caption": "A CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (-) or stimulated for 2 min with anti-CD3 and anti-CD4 antibodies (+). Equal amounts of cell lysates were subjected to affinity purification on Strep-Tactin-Sepharose beads, followed by elution of proteins with D-biotin. Eluted proteins were analyzed by immunoblot with antibodies specific for CBLB and CBL. Equal amounts of proteins from whole cell lysates (WCL) were also probed for CBLB and CBL. Note that in the case of CBLB two bands are detected and likely corresponded to the presence of two isoforms differing at their N-terminus (http://www.uniprot.org/uniprot/Q3TTA7). Also shown are loading control corresponding to the same immunoblot probed with anti-CD5, and molecular masses (kDa). Data are representative of at least three experiments.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (unstim) or stimulated for 30, 120, 300 or 600 seconds with anti-CD3 and anti-CD4 antibodies. Equal amounts of cell lysates were subjected to affinity purification using Strep-Tactin-Sepharose beads and subjected to MS analysis as described in Material and Methods.A Histogram comparing the normalized CBL protein intensities resulting from AP-MS analysis of CD4+T cells from WT and CBLOSTmice prior to and after the specified stimulation times. For each time point, the distributions of the normalized intensities of the 9 data points (3 biological replicates x 3 technical replicates) corresponding to CD4+ T from wild-type (WT) and CBLOSTmice were compared using the adjusted p-value from a one-way ANOVA test (denoted as p(t)) and the value r(t) corresponding to the enrichment observed in the CBLOST samples as compared to WT samples. Different colors represent distinct biological replicates.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (unstim) or stimulated for 30, 120, 300 or 600 seconds with anti-CD3 and anti-CD4 antibodies. Equal amounts of cell lysates were subjected to affinity purification using Strep-Tactin-Sepharose beads and subjected to MS analysis as described in Material and Methods.B Proteins are classified as CBL interactors according to their position in a volcano plot in which the mean p-valueis plotted against the corresponding mean enrichment for CBL(t)>(t)>OST versus WT samples. The time point shown corresponds to the unstimulated condition (t=0s). Mean was calculated using bootstrap resampling (see Results and Material and Methods). Proteins that displayed an enrichment r(t) greater than 2-fold and a corresponding p-value p(t) lower than a set threshold (see Material and Methods) in more than 90% of the bootstrap iterations were selected as specific partners (indicated in red). Names of four of the most significantly enriched proteins are indicated. Dashed lines represent thresholds on the p-value p*=10-3 and the enrichment r*=2 used to identify specific interactors of CBL.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (unstim) or stimulated for 30, 120, 300 or 600 seconds with anti-CD3 and anti-CD4 antibodies. Equal amounts of cell lysates were subjected to affinity purification using Strep-Tactin-Sepharose beads and subjected to MS analysis as described in Material and Methods.C, D List of specific interacting partners of CBLB (C) and CBL (D) ranked according to their maximum mean enrichment across all time points. Heat maps show, for each time point, the fraction of bootstrap iterations for which the corresponding proteins were detected as specific partners (denoted as \"P(Detection)\"). Red dots indicate the proteins that have been previously reported as CBLB (C) interactors in the BioGRID database. Ubiquitin (UB) is highlighted with a black arrow.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (unstim) or stimulated for 30, 120, 300 or 600 seconds with anti-CD3 and anti-CD4 antibodies. Equal amounts of cell lysates were subjected to affinity purification using Strep-Tactin-Sepharose beads and subjected to MS analysis as described in Material and Methods.C, D List of specific interacting partners of CBLB (C) and CBL (D) ranked according to their maximum mean enrichment across all time points. Heat maps show, for each time point, the fraction of bootstrap iterations for which the corresponding proteins were detected as specific partners (denoted as \"P(Detection)\"). Red dots indicate the proteins that have been previously reported as CBL (D) interactors in the BioGRID database. Ubiquitin (UB) is highlighted with a black arrow.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (unstim) or stimulated for 30, 120, 300 or 600 seconds with anti-CD3 and anti-CD4 antibodies. Equal amounts of cell lysates were subjected to affinity purification using Strep-Tactin-Sepharose beads and subjected to MS analysis as described in Material and Methods.E Histograms showing the numbers of specific interactors binding to the CBL-OST or CBLB-OST proteins prior to and after TCR stimulation for different times and for which P(Detection) >0.9.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "A CD4+T cells from wild-type (WT), CBLOST and CBLBOSTmice were left unstimulated (-) or stimulated for 1 min with anti-CD3 and anti-CD4 antibodies (+). Equal amounts of cell lysates were subjected to affinity purification on Strep-Tactin-Sepharose beads and the resulting protein eluates were analyzed by immunoblotting with anti-ubiquitin (UB), anti-CBLB or anti-CBL antibodies. Also shown are a loading control corresponding to equal amounts of proteins from whole cell lysates (WCL) probed with anti-CD5, and molecular masses (kDa). TCR stimulation resulted in some CBLB degradation and in the detection of a higher molecular weight CBLB form, likely due to its ubiquitylation (marked with an asterisk). In contrast, no degradation of CBL was detectable upon TCR stimulation and its molecular weight remained unchanged. Molecular masses are shown (kDa). Data are representative of at least 2 experiments.",
    "ncbi_link": "CBL: 12402
CBLB: 208650"
  },
  {
    "caption": "C Immunoprecipitation of CBL from cell lysates of CD4+T cells isolated from WT or CBLB-deficient mouse (Cblb-/-) and kept unstimulated (-) or stimulated as in (A). Immunoprecipitates and whole cell lystates (WCLs) were analyzed by immunoblot with antibodies specific for the proteins specified in the left margin. Molecular masses are shown (kDa). Data are representative of at least 2 experiments.",
    "ncbi_link": "Cblb: 208650"
  },
  {
    "caption": "D Immunoprecipitation of CBLB from cell lysates of CD4+T cells isolated from WT or CBL-deficient mouse (Cbl-/-) and kept unstimulated (-) or stimulated as in (A). Immunoprecipitates and whole cell lystates (WCLs) were analyzed by immunoblot with antibodies specific for the proteins specified in the left margin. Molecular masses are shown (kDa). Data are representative of at least 3 experiments.",
    "ncbi_link": "Cbl: 12402"
  },
  {
    "caption": "A, B CD4+T cells from wild-type, Cblb-/- and Cd5-/- mice were stimulated for 1 min with anti-CD3 and anti-CD4 antibodies (+). CBL (A) were immunoprecipitated from equal amounts of protein lysates. Level of ubiquitylation and amount of CD5 associated proteins were evaluated by immunoblot with antibodies specific for the proteins specified in the left margin. Whole cell lystates (WCLs) were also analyzed with the specified antibodies. Molecular masses are shown (kDa). Data are representative of at least 2 experiments.",
    "ncbi_link": "Cblb: 208650
Cd5: 12507"
  },
  {
    "caption": "A, B CD4+T cells from wild-type, Cblb-/- and Cd5-/- mice were stimulated for 1 min with anti-CD3 and anti-CD4 antibodies (+). PI3KR1 (PI3Kp85α) (B) were immunoprecipitated from equal amounts of protein lysates. Level of ubiquitylation and amount of CD5 associated proteins were evaluated by immunoblot with antibodies specific for the proteins specified in the left margin. Whole cell lystates (WCLs) were also analyzed with the specified antibodies. Molecular masses are shown (kDa). Data are representative of at least 2 experiments.",
    "ncbi_link": "Cblb: 208650
Cd5: 12507"
  },
  {
    "caption": "(A) Chromatin features mapped here displayed differences between CLL (patient CLL1) and an NBC donor (H7) as shown for the TCF4 locus, which encodes for a transcription factor from the E protein family. Based on the increased H3K4me1, H3K27ac and ATAC signal, two predicted enhancer loci were marked that became active in CLL. Note that the y-axis for RNA-seq is scaled differently for CLL (8000) and NBCs (100) to visualize that the TCF4 gene was not completely silenced but lowly expressed also in NBCs as evident also from the H3K36me3 mark. Light grey depicts active chromatin region and dark grey the confined enhancer locus coinciding with an open chromatin region.",
    "ncbi_link": "TCF4: 6925"
  },
  {
    "caption": "(D) Exemplary region at the TAF13 promoter showing higher H3K4me3 levels upstream of the TSS with lost ATAC signal (grey bar) as compared to the NBC control.",
    "ncbi_link": "TAF13: 6884"
  },
  {
    "caption": "(E) TF motif analysis of ATAC signal lost at CLL promoters with broadened H3K4me3 regions. An enrichment for the NFY TF motif was detected.",
    "ncbi_link": "ATAC: 6375"
  },
  {
    "caption": "(E) Volcano plot of differential super-enhancers targeting known leukemia and cancer genes. Examples include SE loss at CDKN1A, PI3KC2B and KMT2B (MLL2) and SE gain at FMOD, CREB3L2, CTLA4, TCF4, LEF1 and BCL2. Points represent non-differential SEs (grey), and differential SEs (FDR < 0.01) with fold change greater than 1 (orange).",
    "ncbi_link": "BCL2: 596
CDKN1A: 1026
CREB3L2: 64764
CTLA4: 1493
FMOD: 2331
KMT2B: 9757
MLL2: 8085
LEF1: 51176
PI3KC2B: 5287
TCF4: 6925"
  },
  {
    "caption": "(I) Genome browser view of H3K27ac tracks (in grey) at exemplary genes for NBCs and CLL cells 24 hours after mock and after panobinostat treatment. At genes such as CDKN1A (cell cycle control) and KLF13, reduced H3K27ac signal in CLL was increased upon HDAC inhibition to the level found in NBCs. WNT11 is shown as an example of a de novo gain of an active enhancer due to treatment with panobinostat.",
    "ncbi_link": "CDKN1A: 1026
KLF13: 51621
WNT11: 7481"
  },
  {
    "caption": "(B) H3K27ac (left) and DNA methylation (right) at NFAT binding sites. CLL cells showed both an H3K27ac enrichment and DNA-hypomethylation at NFAT target sites, suggesting a higher activity of TFs from the NFAT family in CLL.",
    "ncbi_link": "NFAT: 4776///4775///10725///4773///4772"
  },
  {
    "caption": "(D) ATAC footprints for E2A, EBF and CTCF motifs from the Homer analysis. The E2A motif footprint (binding site of E protein family TFs like TCF4) displayed an increased binding signal in CLL while sites with the EBF and CTCF motif lost the ATAC signal.",
    "ncbi_link": "CTCF: 10664
EBF: 1879
E2A: 6929
ATAC: 6375"
  },
  {
    "caption": "(E) Expression of the genes nearest to target enhancers with constitutively bound ("stable") CTCF vs. enhancers that lost CTCF in CLL. Loss of CTCF binding correlated with reduced gene expression.",
    "ncbi_link": "CTCF: 10664"
  },
  {
    "caption": "(G) Enhancer-promoter rewiring at the NFKB2 locus. A switch of interactions between the NFKB2 promoter and two different enhancers in CLL (red line) vs. NBCs (grey line) was observed. Based on the CTCF ChIP-seq analysis both intronic enhancers at the NFKB2 and the FBXL15 gene show (nearby) constitutively bound CTCF, even though the targets of the two enhancers are switched.",
    "ncbi_link": "CTCF: 10664
FBXL15: 79176
NFKB2: 4791"
  },
  {
    "caption": "(E) Analysis of regulation of SNX22 by the intronic H464 enhancer shown in panel B. This enhancer lost its ATAC signal at the predicted EBF1 binding site. EBF1 ChIP-seq analysis validated that EBF1 is indeed lost at this site. Although H3K27ac at the locus was only slightly reduced, transcription of SNX22 was largely reduced. These findings are consistent with a mechanism where EBF1 binding drives gene expression of SNX22 by binding to H464.",
    "ncbi_link": "EBF1: 1879
SNX22: 79856
ATAC: 6375"
  },
  {
    "caption": "(G) The protein level of SMIM26  (up) and RNA level of LINC00493  (down) in ccRCC  tissues (T) and their adjacent non-tumoral tissues (N) were detected by IHC staining  and RNA in situ hybridization  (ISH) staining. The right scatter plot shows no significant correlation between SMIM26 protein expression  and LINC00493  RNA expression in ccRCC  tissues (green dots, P=0.94) and adjacent non-tumorous renal  tissues (purple dots, P=0.53). n = 72. Scale bar, 200 μm.",
    "ncbi_link": "LINC00493: 388789"
  },
  {
    "caption": "(F) RIP  assay showing a strong binding  of LINC00493  with PABPC4  in HEK293T  and ACHN  cells.",
    "ncbi_link": "LINC00493: 388789"
  },
  {
    "caption": "(G) RNA levels of SMIM26  were determined by qRT-PCR in PABPC4  knockdown cells. Data are shown as mean ± SEM of three biological replicates. Unpaired two-tailed Student's t-test. n.s, nonsignificant. Bars, SEM.",
    "ncbi_link": "PABPC4: 8761
SMIM26: 388789"
  },
  {
    "caption": "(I) Knocking down PABPC4  could not significantly alter the degradation half-life  of SMIM26  protein. Data are shown as mean ± SEM of three biological replicates.",
    "ncbi_link": "PABPC4: 8761"
  },
  {
    "caption": "(J) RNC  of SMIM26  was detected in HEK293T  and ACHN  cells transfected with anti-PABPC4  siRNAs. Unpaired two-tailed Student's t-test, ***P < 0.001. Data are shown as mean ± SEM of three biological replicates.",
    "ncbi_link": "PABPC4: 8761
SMIM26: 388789"
  },
  {
    "caption": "(F) Western blotting showed that mesenchymal  marker of Vimentin  and Fibronectin  was decreased, and  E-cadherin was increased in SMIM26-overexpressing cells.",
    "ncbi_link": "SMIM26: 388789"
  },
  {
    "caption": "(J) NOD-SCID mice  were transplanted with ACHN-luci  cells with or without overexpression of SMIM26 via tail vein injection, respectively. Bioluminescent was visualized 5 weeks later by using an IVIS 200 Imaging System. Data are shown as mean ± SD of 5 mice  per group. Unpaired two-tailed Student's t-test, ****P < 0.0001. n.s, nonsignificant.",
    "ncbi_link": "luci: 
SMIM26: 388789"
  },
  {
    "caption": "Co-IP  assays were performed to detect the interaction  between SMIM26  and SLC25A11. Lysates from ACHN  cells expressing SMIM26-flag  were  co-immunoprecipitated by anti-flag  antibody (E) SMIM26  and SLC25A11  were detected by western blotting.",
    "ncbi_link": "flag: 
SMIM26: 388789"
  },
  {
    "caption": "(K-L) N-ter domain of SMIM26  fused with GFP-flag interacted  with SLC25A11. The N-ter SMIM26-GFP-flag construct was transfected into HEK293T  cells, co-immunoprecipitation  was performed by using anti-flag  antibody (K) and anti-SLC25A11  antibody (L).",
    "ncbi_link": "flag: 
GFP: 
SMIM26: 388789"
  },
  {
    "caption": "(A-B) Immunoblotting  validation of the p-AKT  at Ser473 expression in ACHN  and  769-P  cells with overexpression (A) or knockdown (B) of SMIM26 compared with their corresponding control.",
    "ncbi_link": "SMIM26: 388789"
  },
  {
    "caption": "(D) Co-IP assays were performed to detect the interaction  between SMIM26  and AGK  in ACHN  and 769-P cells expressing SMIM26-flag. Lysates were co-immunoprecipitated by anti-flag  antibody. (E) Co-IP  assays were performed to detect the interaction  between SMIM26  and AGK  in ACHN  and 769-P cells expressing SMIM26-flag. Lysates were co-immunoprecipitated  by anti-AGK  antibody.",
    "ncbi_link": "flag: 
SMIM26: 388789"
  },
  {
    "caption": "(G) Immunofluorescence  of SMIM26  (purple), AGK  (green) and mitochondrial  (red) in ACHN  cells with or without overexpression of SMIM26. Scale bar, 10 μm. Fluorescence intensity analysis of colocalization  of AGK  and mitochondria  in cells treated with control or SMIM26. ImageJ software was used to analyze the fluorescence colocalization. The red line of statistical analysis centers on the co-location  of AGK  and mitochondria.",
    "ncbi_link": "SMIM26: 388789"
  },
  {
    "caption": "The interaction  of AGK  and SLC25A11  was determined by immunoblotting  in ACHN  and 769-P  cells with control or SMIM26  overexpressing (K)",
    "ncbi_link": "SMIM26: 388789"
  },
  {
    "caption": "The interaction  of AGK  and SLC25A11  was determined by immunoblotting  in ACHN  and 769-P cells with control or SMIM26  knockdown (L).",
    "ncbi_link": "SMIM26: 388789"
  },
  {
    "caption": "A) Left: Representative current traces from wildtype NavMs channels showing the first 0.1 s of 0.5 s activations from -180 mV holding potential recorded with the indicated extracellular cations. Right: Resulting current-voltage profiles profiles, where current magnitudes were normalized to the maximum inward current measured in the sodium condition.B) Left: Representative current traces from mutant channel E178D (as in A). Right: Resulting current-voltage profiles (error ± SEM; n = 6-9 for NavMs; n = 4-8 for E178D).",
    "ncbi_link": "NavMs: "
  },
  {
    "caption": "B Similar to (A), but using HeLa  cells untreated or treated with GCN2  siRNA 48 h before treatment with indicated concentrations of HF  for 5 h. C Similar to (A), but with high HF  concentrations. Data information: Representative results of at least three independent experiments are shown in each panel.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "B Representative immunoblots  of indicated proteins in lysates from HeLa cells after 5 h treatment with indicated concentrations of HF. C Similar to (B), but using HeLa  cells untreated or treated with GCN2  siRNA 48 h before treatment with indicated concentrations of HF. Data information: Representative results of at least three independent experiments are shown in each panel.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "C Newly synthesized proteins in 4KO or 4KO+GCN2 MEF  cells treated with 12.5 or 200 nM HF.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "D Newly synthesized proteins in eIF2αS/S and eIF2αA/A MEF  cells treated with 12.5 or 200 nM HF.",
    "ncbi_link": "eIF2α: 229317"
  },
  {
    "caption": "E Newly synthesized proteins in eIF2αS/S and eIF2αA/A MEF cells treated with indicated concentrations of Tm for 2.5 or 5 h.",
    "ncbi_link": "eIF2α: 229317"
  },
  {
    "caption": "F Newly synthesized proteins in HeLa  cells untreated or treated with GCN2  siRNA 48 h before treatment with indicated concentrations of HF.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "I Newly synthesized proteins in HeLa  cells untreated or treated with GCN2  siRNA 48 h before treatment with indicated concentrations of histidinol (His) or borrelidin  (Bor).",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "A Representative immunofluorescence for  PH3 (green), combined with DAPI staining (white), of E14.5 wildtype (WT) and 11B mouse dorsolateral neocortex  rostrally. B Representative  immunofluorescence for pVim (yellow), combined with DAPI staining (white), of E14.5 WT and 11B mouse dorsolateral neocortex rostrally. Boxes (50 µm x 65 µm) in (B) indicate areas that are shown at higher magnification in (B'). Arrow, pVim+ BP with basal process (mitotic bRG); notched arrowheads, basal process; arrowhead, pVim+ BP without basal process (mitotic bIP). C-E Quantification of PH3+ APs (C), PH3+  BPs (D) and pVim+ bRG (E left) and  bIPs (E right) in a 200 µm-wide field of E14.5 WT (white) and 11B   (black) mouse dorsolateral neocortex rostrally. Note the difference in ordinate scales in (E). F Data information: Images are single optical sections Scale bars, 50 µm 10 µm Data are the mean of 6-19 (WT) and 6-26 (11B) littermate embryos, which were derived from 3-9 separate litters. Error bars indicate SD, two-tailed unpaired Student's t-test, * P < 0.05; ** P < 0.01 P = 0.0269 (D); P = 0.0302 (E, left); P = 0.0139 (E, right)",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "F Representative immunofluorescence for  Pax6 (cyan) and Tbr2 (magenta), combined with DAPI staining (white), of E14.5 WT and 11B mouse dorsolateral neocortex rostrally. Boxes (25 µm x 25 µm) in (F) indicate areas that are shown at higher magnification in (F'). Outlined by dashed white lines, Pax6+ & Tbr2+ BP; outlined by solid white lines, Pax6+ & Tbr2- BP. G-K Quantification of Pax6+ & Tbr2- cells in VZ  (G), Pax6+ & Tbr2+ cells in VZ  (H), Pax6+ & Tbr2- cells in SVZ and IZ (I),  Pax6+ & Tbr2+ cells in SVZ and IZ (J) and  Pax6- & Tbr2+ cells in SVZ and  IZ  (K) in a 200 µm-wide field of E14.5 WT (white) and 11B (black) mouse dorsolateral neocortex rostrally. L Data information:  Images are Z projections of 4 optical sections Scale bars, 50 µm 10 µm Data are the mean of 6-19 (WT) and 6-26 (11B) littermate embryos, which were derived from 3-9 separate litters. Error bars indicate SD, two-tailed unpaired Student's t-test, * P < 0.05; ** P < 0.01 P = 0.0281 (I); P = 0.0088 (J); P = 0.0014 (K)",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "L-N, Sequential  BrdU-EdU labelling.  BrdU was injected into pregnant mice  at E13.5, i.e. 24 hr before sacrifice at E14.5, and EdU was injected into the same pregnant mice 0.5 hr before sacrifice at E14.5. (L) Representative immunofluorescence for BrdU (magenta), combined with  EdU staining (cyan) and DAPI staining (white), of E14.5 WT and 11B mouse dorsolateral neocortex rostrally. (M, N) Quantification of BrdU+ & EdU+ cells (M) and the percentage of BrdU+ cells that are  BrdU+ & EdU+ (N) in VZ  and SVZ  in a 200 µm-wide field of E14.5 WT (white) and 11B (black) mouse dorsolateral neocortex rostrally. Data information: Data are the mean of 6-19 (WT) and 6-26 (11B) littermate embryos, which were derived from 3-9 separate litters. Error bars indicate SD, two-tailed unpaired Student's t-test, * P < 0.05; ** P < 0.01 P = 0.0049 (M, SVZ); P = 0.0323 (N, SVZ).  ",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "H Representative  immunofluorescence for Tbr1 (cyan), Ctip2 (magenta) and Satb2 (green), combined with DAPI staining (white), of E18.5 WT and 11B mouse neocortex at the position where cortical thickness was measured (A, red lines). I Quantification of zone thickness of E18.5 WT (white) and 11B (black) mouse neocortex  at the position where cortical thickness was measured (A, red lines). J Data information:  Images are single optical sections Scale bar, 20 µm Data are the mean of 7 (WT) and 8-12 (11B) littermate embryos, which were derived from 4 separate litters. Error bars indicate SD. Two-way ANOVA, followed by Bonferroni's multiple comparisons test (B-D); two-tailed unpaired Student's t-test P = 0.0287 (I, IZ); P = 0.0039",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "A Dorsal  view of adult wildtype (WT) and 11B mouse brain at P56. Orange lines illustrate the measurements of neocortex width and  length; red lines illustrate the measurements of neocortex area. B, C Quantification of neocortex width, length and area. D Data information: Scale bar, 1 mm Data are the mean of 8 (WT) and 8 (11B) adult littermate mice. Error bars indicate SD, two-tailed unpaired Student's t-test , * P < 0.05, ** P < 0.01, **** P < 0.0001. P < 0.0001 (B,  neocortex width); P < 0.0001 (C)",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "G, H Representative immunofluorescence for Ctip2 (magenta), Satb2 (green) and Brn2 (yellow), combined with DAPI staining (white), of P56 adult WT and 11B mouse neocortex  at the position where cortical thickness was measured (D, red lines). Data information: Images are single optical sections Scale bar, 20 µm",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": "IntelliCage was used to evaluate the memory flexibility of adult 11B mice. Four separate sessions were carried out: (i) 5 WT males together with 5 11B males; (ii) 5 other WT males together with 5 other 11B males; (iii) 5 WT females together with 7 11B females; (iv) 4 other WT females together with 8 other 11B females. Data are the mean of the total 10 males (WT), 10 males  (11B), 9  females (WT) and 15 females  (11B) adult littermate  mice. Data points were obtained at consecutive days, error bars indicate SD. (A, B) Quantification of the discrimination error rate in the first 100 visits during the drinking phase of the acquisition stage of adult wildtype (WT) and 11B mice (male, A; female, B) in the IntelliCage. Overall place learning performance of WT and 11B mice was analysed using two-way ANOVA followed by Fisher's LSD test; all data points during the acquisition phase were included. For males (A), WT vs. 11B, P > 0.05; data over time, **** P < 0.0001; interaction, P > 0.05. For females (B), WT vs. 11B, P > 0.05; data over time, **** P < 0.0001; interaction, P > 0.05. Note that (i) the two male sessions and the two female sessions yielded essentially the same results, and (ii) not shown in panels the two separate male  sessions yielded essentially the same results, and the two separate female  sessions yielded essentially the same results.",
    "ncbi_link": "11B: 89839"
  },
  {
    "caption": " (A RNA sequencing of CD31 and CD34 double-positive retinal endothelial cells from P5 wild-type mice. (A) RNA levels (FPKM; fragments per kilobase million) of marker genes of endothelial cells (green; CD31 (gene name PECAM1), CD34, von Willebrand Factor (vWF), tyrosine-protein kinase receptor Tie2 (TEK), VE-cadherin (CDH5), endoglin (ENG), CD146 (MCAM) and VEGFR2 (KDR)), astrocytes (blue, GFAP), immune cells (red; T-cells (CD3E), B-cells (CD19), all leucocytes (CD45, PTPRC), and monocytes/macrophages (F4/80, EMR1)), Müller glia cells (orange; aquaporin 4 (AQP4)), neurons (yellow; retinal ganglion cells (RNA binding fox-1 homolog 3, RBFOX3), amacrine cells (parvalbumin, PVALB), bipolar cells (PKC-α, PRKCA), horizontal cell (calbindin, CALB1), photoreceptors (rods, CD73 (NT5E); cones, transducing (GNAT1)), and retinal pigment epithelial cells (magenta; retinal pigment epithelium-specific 65 kDa protein (RPE65). ",
    "ncbi_link": "EMR1: 13733
F4/80: 13733
AQP4: 11829
aquaporin 4: 11829
CALB1: 12307
calbindin: 12307
CD19: 12478
CD34: 12490
CD3E: 12501
CDH5: 12562
VE-cadherin: 12562
endoglin: 13805
ENG: 13805
GFAP: 14580
GNAT1: 14685
KDR: 16542
VEGFR2: 16542
CD146: 84004
MCAM: 84004
CD73: 23959
NT5E: 23959
CD31: 18613
PECAM1: 18613
PKC-α: 18750
PRKCA: 18750
CD45: 19264
PTPRC: 19264
parvalbumin: 19293
PVALB: 19293
RBFOX3: 52897
RNA binding fox-1 homolog 3: 52897
retinal pigment epithelium-specific 65 kDa protein: 19892
RPE65: 19892
TEK: 21687
tyrosine-protein kinase receptor Tie2: 21687
von Willebrand Factor: 22371
vWF: 22371"
  },
  {
    "caption": " B) RNA sequencing of CD31 and CD34 double-positive retinal endothelial cells from P5 wild-type mice. (B) RNA levels of VASP (red), EVL (green) and Mena (blue) in the CD31 and CD34 double-positive P5 retinal endothelial cells. Error bars represent SEM; n = 18 animals (36 retinas) from six independent litters; four independent experiments. ***p<0.001, one-way ANOVA with Bonferroni's multi comparison test. ",
    "ncbi_link": "Mena: 13800
EVL: 14026
VASP: 22323"
  },
  {
    "caption": " (A) Wild-type and EVL-/- P5 retinas were digested, labelled with CD31-, CD34- and EVL-specific antibodies and analyzed by flow cytometry. Endothelial cells were defined as CD31/CD34-double positive cells (gate indicated in the left panel) and analyzed for EVL expression (middle panel). Mean fluorescence intensity (MFI) of EVL in wild-type (magenta) and EVL-/- (black) cells is shown in the right panel. WT: n=3, EVL-/-: n=2; two retinas per animal. Error bars represent SEM. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (B-C) EVL protein expression in sparse/migrating wild-type (WT) and EVL-/- mouse brain endothelial cells (MBEC) and mouse lung endothelial cells (MLEC). Actin was used as loading control. Western blots are representative of three independent experiments. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (D) MLEC from wild-type (upper panel) and EVL-/- (lower panel) mice stimulated with 10 ng/ml VEGF were stained for actin (cyan) and EVL (magenta). Asterisks indicate focal adhesions, white arrows indicate filopodia and white arrowheads indicate the leading edge of lamellipodia. Representative images from four independent experiments are shown. Scale bar, 20 µm. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (A) Isolectin B4 stained vasculature in whole mount retinas of wild-type (WT) and global EVL-/- mice on postnatal days 3, 5 and 7 (P3, P5, P7) assessed by confocal microscopy. Scale bars 200 µm. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (B) Analysis of the radial vascular outgrowth relative to retinal radius and normalized to wild-type littermates. (C) Impact of individual and combined VASP/EVL deletion on sprouting angiogenesis in the postnatal mouse retina at P5 (EVL-deficient animals (E-/-), green; VASP-deficient animals (V-/-), red; VASP/EVL-double deficient animals (EV-/-), orange). ",
    "ncbi_link": "EVL: 14026
VASP: 22323"
  },
  {
    "caption": " The retinal vasculature of endothelial cell specific EVL knockout mice (EVLΔEC) and littermate controls (EVLfl/fl) on P5 was analyzed by Isolectin B4 staining. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " Radial outgrowth of the retinal vasculature; in global EVL-/- mice are shown for comparison; 4 - 5 independent experiments. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " CD31 and CD34 double positive endothelial cells were isolated from wild-type or EVL-/- P5 retinas by FACS and analyzed by RNA-sequencing. Two independent experiments; in total 18 retinas from WT mice and 18 retinas from EVL-/- mice from three different litters, each. (A) RNA levels (FPKM) of VASP, EVL and Mena in endothelial cells from wild-type or EVL-/- retinas. Error bars represent SEM. ",
    "ncbi_link": "Mena: 13800
EVL: 14026
VASP: 22323"
  },
  {
    "caption": " (D) Analysis of mRNA levels of Esm1, Ptgs2 (cyclooxygenase 2), serpine 1 and paxillin in EVL-deficient MLEC relative to WT controls set to 100. n = 3-4 independent experiments, error bars represent SEM, one sample t-test, *p<0.05; **p<0.01. ",
    "ncbi_link": "Esm1: 71690
EVL: 14026
cyclooxygenase 2: 19225
Ptgs2: 19225
paxillin: 19303
serpine 1: 18787"
  },
  {
    "caption": " (E) ESM1 protein expression in P5 retinas of wild-type (WT) and global EVL-/- mice. Retinas were fixed and stained with isolectin B4 (IB4, green) to visualize endothelial cells and antibodies directed against the tip cell marker ESM1 (red). Representative images from three independent experiments are shown. Scale bars, 100 µm. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (A) Proliferation of WT and EVL-/- MLEC was assessed by BrdU incorporation. The number of BrdU positive cells (red) was normalized to the total number of cells (white). Eight fields of view per condition and genotype for each of 5 independent WT and EVL-/- cell batches; error bars represent SEM; **p<0.01, ***p<0.001, #p=0.171 non-significant vs. Basal EVL-/-, one-way ANOVA with Bonferroni's multi comparison test; scale bar = 50 µm. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (B) Cumulative length of CD31-positive sprouts from WT and EVL-/- aortic rings embedded in collagen after 5 days without (basal) or with VEGF stimulation (30 ng/ml). 7 WT and 6 EVL-/- adult animals from three different litters, each; 3 aortic rings per animal and condition; error bars represent SEM; **p<0.01; ***p<0.01; #p=0.543 non-significant vs. basal EVL-/-, one-way ANOVA with Bonferroni's multi comparison test; scale bar, 250 µm.",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (C) Sprouting of WT and EVL-/- primary MLEC spheres in the absence (Basal) or presence of VEGF (50 ng/ml); asterisks indicate sprouts; scale bars, 100 µm. (D) Solid bars represent proportion of WT and EVL-/- MLEC spheres forming sprouts in the absence (−) or presence (+) of VEGF. n-numbers are indicated; n.s. non-significant (p=0.557); ***p<0.001, Fisher's exact test. (E) Quantification of MLEC sphere sprout length without or with VEGF. Dots represent individual sprouts. Horizontal lines represent mean, error bars represent SEM. n = 20-30 beads (from three independent experiments). ***p<0.001, n.s. non-significant (p=0.543), one-way ANOVA with Bonferroni's multi comparison test. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (A) VEGFR2 protein levels in wild-type (WT) and EVL-deficient (EVL-/-) endothelial cells. Actin was used as loading control. The lower panel shows quantification of VEGFR2 to actin ratios from five independent cell batches; error bars represent SEM; n.s. non-significant (p=0.388), unpaired Student's t-test. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (B) Antibody feeding assay to monitor VEGFR2 internalization after VEGF stimulation. Left panel: schematic diagram showing the two step staining procedure of surface and internalized VEGFR2 antibodies, which are displayed in yellow and green in the merged confocal images of WT and EVL-/- endothelial cells (middle panel), respectively; scale bar, 10 µm. The bar graphs show quantification of the number of VEGFR2 clusters and the ratio of internalized to total VEGFR2 ratios normalized to wild-type; n = 4-6 independent cell batches, error bars represent SEM; **p<0.01, ***p<0.001, unpaired Student's t-test. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (A) Western blots and quantification of VEGFR2 phosphorylation levels relative to total VEGFR2 levels in WT and EVL-/- endothelial cells under basal and VEGF-stimulated conditions (80 ng/ml); n = 5 independent cell batches, error bars represent SEM; *p<0.05, one-way ANOVA with Bonferroni's multi comparison test. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (B) Western blots and quantification of ERK1/2 phosphorylation levels relative to total ERK levels in WT and EVL-/- endothelial cells under basal and VEGF-stimulated conditions (80 ng/ml); n = 6 independent cell batches, error bars represent SEM; *p<0.05, one-way ANOVA with Bonferroni's multi comparison test. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " (C) ERK1/2 phosphorylation in P5 retinas of wild-type (WT) and global EVL-/- mice. Retinas were fixed and stained with isolectin B4 (IB4, green) to visualize endothelial cells and antibodies directed against phospho-ERK1/2 (red). Representative images from three independent experiments are shown. Scale bars, 100 µm. (D) Analysis of endothelial ERK1/2-phosphorylation normalized to wild-type littermates. Error bars represent SEM; ***p<0.001, unpaired Student's t-test; two different litters. ",
    "ncbi_link": "EVL: 14026"
  },
  {
    "caption": " B. Rif1-∆C594 retains function to control DNA replication. Growth of a cdc7-1 rif1-∆C594 mutant was compared with growth of cdc7-1 RIF1 and cdc7-1 rif1∆ strains at 23ºC (permissive temperature for cdc7-1 allele), 26ºC (mild restrictive temperature) and 30ºC (strict restrictive temperature) ",
    "ncbi_link": "cdc7: 851545
Rif1: 852578
rif1: 852578
RIF1: 852578"
  },
  {
    "caption": " A. Specimen overview of Chromosome VI-left region showing results of ChIP-Seq analysis of Rif1 and Rif1-∆C594 proteins. ChIP sequence reads were normalised against sequence reads from corresponding input samples, and relative enrichment is plotted for Chromosome VI coordinates 1-80,000. Y-axis shows enrichment values (linear scale, range is 0 to 3.5). Values below 1 are shown in grey, and values above 1 (i.e. sequences enriched in ChIP samples) are coloured blue (Rif1) and red (Rif1-∆C594). Plots show ChIP analysis results from cells arrested by α-factor (G1), released from α-factor at 16ºC for 60 min and 90 min, or released from α-factor into 0.2 M HU for 60 min at 23ºC ",
    "ncbi_link": "Chromosome VI: 
Rif1: 852578"
  },
  {
    "caption": " B. Rap1-dependent association of Rif1 with the promoter regions of Rap1-controlled genes. ChIP enrichment around PAU3 (left) and MAM3 (right), both genes whose transcription is controlled by Rap1. Values above 1 (i.e. enriched) shown by overlaid blue and red histograms for Rif1 and Rif1-∆C594, respectively. Values below 1 shown in grey ",
    "ncbi_link": "MAM3: 854094
PAU3: 850468
Rif1: 852578"
  },
  {
    "caption": " A. ChIP-Seq analysis of Rif1 and Rif1-∆C594 proteins shows tRNA gene and origin binding, with widened peaks at early origins ARS606 and ARS607 in HU block. Plots show Chromosome VI genome coordinates 160,000- 210,000. Plot colours here and in following Figures are as in Fig 2B. Widened peaks are not observed in unperturbed S phase samples, or for Rif1-∆C594 ",
    "ncbi_link": "ARS606: 
ARS607: 
Chromosome VI: "
  },
  {
    "caption": " B. Association of Rif1-∆C594 at replication origins is enhanced in HU block. ChIP enrichment of Rif1 and Rif1-∆C594 around early origin ARS1426 (left) and late origin ARS1412 (right) ",
    "ncbi_link": "ARS1412: 
ARS1426: "
  },
  {
    "caption": " C. Differential association of Rif1 and Rif1-∆C594 to centromeres. ChIP enrichment of Rif1 and Rif1-∆C594 around the CEN4 locus ",
    "ncbi_link": "CEN4: "
  },
  {
    "caption": " A. ChIP-qPCR confirmation of Rif1 and Rif1-∆C594 association with replication origins. ChIP was performed using cells arrested in α-factor (open bars) or HU (grey bars), and qPCR analysis performed for early origin ARS1426 (left) and late origin ARS1412 (right). Values shown are 'normalised ChIP efficiencies' obtained by subtracting the value obtained at a control locus (see Materials and Methods). Bars indicate the averages of two biological replicates, with values from each replicate shown by open circles ",
    "ncbi_link": "ARS1412: 
ARS1426: "
  },
  {
    "caption": " C. Replication timing programme is intact in rif1-∆C594 cells. Replication of selected origins at an HU block analysed by BrdU incorporation. Cells were synchronised by α-factor  and released into the medium containing 0.2 M HU and 1.13 mM BrdU. Plots show the percentage of total ARS607, ARS422.5, or ARS1412 DNA pulled down by IP with anti-BrdU, calculated from two biological replicate samples. Bars indicate the average of two biological replicates and open circles the values from each replicate. Insets in ARS422,5 and ARS1412 panels show the same data with Y-axis scales adjusted to 0 - 0.03% ",
    "ncbi_link": "ARS1412: 
ARS422,5: 
ARS422.5: 
ARS607: 
rif1: 852578"
  },
  {
    "caption": "b, Upon rapamycin treatment (300 nM) LC3 conversion and downregulation of H4K16ac are observed in WT MEF cells but not in the autophagy-deficient atg5−/− and atg7−/− MEF cells.",
    "ncbi_link": "atg5: 11793
atg7: 74244"
  },
  {
    "caption": "c, Rapamycin treatment increased the LC3-II/LC3-I ratio and promoted H4K16ac decrease in sirt1−/− and WT MEF cells.",
    "ncbi_link": "sirt1: 93759"
  },
  {
    "caption": "h, Overexpression of Sas2 repressed the downregulation of H4K16ac upon rapamycin treatment.",
    "ncbi_link": "Sas2: 855157"
  },
  {
    "caption": "e, f, Increasing H4K16ac levels by either overexpression of hMOF, inhibition of SIRT1 by siRNA or the chemical inhibitor Ex527 promoted cell death upon rapamycin treatment.",
    "ncbi_link": "hMOF: 84148
SIRT1: 23411"
  },
  {
    "caption": "(C) Brucella replication in  BMMs  expressing either  GFP or GFP-BspF and infected with either wild type (2308), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria, measured as number of bacteria per cell at 24 h pi. Data are means ± SD of n=3 independent experiments. Grey dots represent values from individual cells analyzed (n>300); black dots indicate means of individual experiments. Asterisks indicate statistically significant differences (P<0.05, two-way ANOVA followed by Dunnett's multiple comparisons test) compared to controls.",
    "ncbi_link": "GFP: 
BspF: 3788412
bspF: 3788412"
  },
  {
    "caption": "(A) Quantification of ss-eGFP-FKBPF36M trafficking in HeLa(M)-C1 cells transfected for 24 h with pmCherry (mCherry) or pmCherry-BspF (mCherry-BspF). Rapamycin was added to initiate secretory traffic of ss-eGFP-FKBPF36M and its colocalization with calnexin (ER), ERGIC-53 (ERGIC), GM130  (Golgi), p230  (TGN), or secretory vesicles (SV) was scored over a 60 min time course. Data are means ± SD from n=3 independent experiments. Asterisks indicate statistically significant differences between mCherry- and mCherry-BspF-expressing cells as determined by a two-way ANOVA with Sidak's multiple comparisons test (P<0.05).",
    "ncbi_link": "mCherry: 
BspF: 3788412"
  },
  {
    "caption": "(A) Representative confocal fluorescence micrographs of HeLa  cells transfected for 24 h to produce either  mCherry or mCherry-BspF  (grayscale panels), incubated on ice with AlexaFluor™488-Cholera Toxin subunit B  (CTxB; green) and shifted to 37˚C for 20 min to allow for CTxB retrograde transport to the Golgi apparatus (stained using an anti-GM130 antibody; purple). CTxB accumulation within Golgi  structures appears white in overlays. Scale bars: 10 and 2 µm (insets). (B) Quantification of  CTxB transport to the Golgi apparatus in HeLa  cells producing either mCherry, mCherry-BspF or HA-BspF over a 30 min time course, expressed as percentages of cells in which  CTxB colocalized  with the GM130 Golgi marker, as in (A). Data are means ± SD from n=3 independent experiments, in which 100 cells were analyzed per experiment. Asterisks indicate statistically significant differences compared to mCherry-producing cells as determined by a two-way ANOVA with Tukey's multiple comparisons test (P<0.05). ( ",
    "ncbi_link": "HA: 
mCherry: 
BspF: 3788412"
  },
  {
    "caption": "(D) Quantification of CTxB  transport to the Golgi apparatus in BMMs following siRNA-mediated depletion of either Arf6 (siArf6), Rab8a (siRab8a) or Rab6a/a' (siRab6a/a') after AlexaFluor™488-CTxB binding on ice followed by 30 min incubation at 37˚C. Data are means ± SD from n=3 independent experiments, in which 100 cells were analyzed per experiment. Asterisks indicate a statistically significant difference compared to siNT control cells as determined by a one-way ANOVA with Tukey's multiple comparisons test (P<0.05). (E) Quantification of  CTxB transport to the Golgi apparatus in BMMs that were either mock-infected or infected with wild type (2308), ΔbspF, complemented ∆bspF (ΔbspF::bspF), ∆bspB  or complemented ∆bspB (ΔbspB::bspB) bacteria for 24 h, incubated for 30 min with  AlexaFluor™488-CTxB  on ice for  binding  followed by 30 min incubation at 37˚C. Data are means ± SD from n=3 independent experiments, in which 100 cells were analyzed per experiment. Asterisks indicate a statistically significant difference compared to mock-infected cells as determined by a one-way ANOVA with Tukey's multiple comparisons test (P<0.05). ( ",
    "ncbi_link": "Arf6: 11845
bspB: 3787425
bspF: 3788412
Rab6a: 19346
Rab8a: 17274"
  },
  {
    "caption": "(G-I) Brucella replication in BMMs  treated with non-targeting siRNAs (siNT), or siRNAs against Rab6a/a' (siRab6a/a') (G), Rab8a (siRab8a) (H) or Arf6  (siArf6) (I) and infected with either wild type (2308), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria, measured as number of bacteria per cell at 24 h pi. Data are means ± SD of n=3 independent experiments in which at least 100 cells were analyzed per experiment. Grey dots represent individual cells analyzed; black dots indicate means of individual experiments. Asterisks indicate statistically significant differences (P<0.05, one-way ANOVA followed by Dunnett's multiple comparisons test) between test and control conditions.",
    "ncbi_link": "Arf6: 11845
bspF: 3788412
Rab6a: 19346
Rab8a: 17274"
  },
  {
    "caption": "(E) Bacterial replication in BMMs  transduced to either produce GFP, GFP-ACAP1 or GFP-ACAP1R448Q and infected with either wild type (2308), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria for 24 h. Data are means ± SD of n=3 independent experiments, in which at least 100 cells were analyzed per experiment. Grey dots represent individual cells analyzed (n>300); black dots indicate means of individual experiments. Asterisks indicate statistically significant differences (P<0.05, two-way ANOVA followed by Dunnett's multiple comparisons test) between test and control conditions.",
    "ncbi_link": "GFP: 
ACAP1: 9744
bspF: 3788412"
  },
  {
    "caption": "(D-F) Recruitment of Stx6-positive  vesicles to rBCVs in  BMMs treated with non-targeting siRNAs (siNT), siRNAs against Arf6  (siArf6) (D), Rab8a (siRab8a) (E) or Rab6a/a' (siRab6a/a') (F) and infected for 24 h with either wild type (2308), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria. Data are means ± SD of n=3 independent experiments, in which 200 BCVs were analyzed per experiment. Asterisks indicate statistically significant differences (P<0.05, one-way ANOVA followed by Dunnett's multiple comparisons test) between test and control conditions; ns, not significant.",
    "ncbi_link": "Arf6: 11845
bspF: 3788412
Rab6a: 19346
Rab8a: 17274"
  },
  {
    "caption": "(H) Brucella  replication in BMMs treated with either non-targeting siRNAs (siNT), or siRNAs against Stx6  (siStx6) and infected for 24 h with either wild type (2308), ΔbspF, or complemented ∆bspF (ΔbspF::bspF) bacteria. Data are means ± SD of n=3 independent experiments, in which at least 100 cells were analyzed per experiment. Grey dots represent individual cells analyzed (n>300); black dots indicate means of individual experiments. Asterisks indicate statistically significant differences (P<0.05, one-way ANOVA followed by Dunnett's multiple comparisons test) between test and control conditions.",
    "ncbi_link": "bspF: 3788412
Stx6: 58244"
  },
  {
    "caption": "Microarray analysis was performed following doxycycline-regulated specific AR-V7 depletion (using a tet-plKO backbone) in 22Rv1 PC cells compared to doxycycline-treated shGFP controls. The genes that were significantly regulated by shAR-V7 (in either direction, p value < 0.05) were distributed among the gene modules defined by WGCNA in panel A. Upregulated genes (red) are those in which expression decreased following AR-V7 depletion and conversely downregulated genes (blue) are those that increased following AR-V7 depletion.",
    "ncbi_link": "GFP: 
AR: 367"
  },
  {
    "caption": "Hornberg et al., 2011 gene expression profiling array data was analyzed to determine the expression levels of the seven genes in human CRPC bone metastases, grouped by their relative levels of AR-VS, mainly AR-V7. (High-levels of AR-V7 (top quartile) or lower levels of AR-V7 (quartiles 1-3). Data are plotted as the mean ± s.e.m.. Non-parametric Mann-Whitney test was performed (two-tailed). Note that BUB1B expression was not measured in these microarrays. ** Significant at a p value < 0.05. N (AR-V7 low) = 20; N (AR-V7 high) = 10.",
    "ncbi_link": "BUB1B: 701"
  },
  {
    "caption": "Cell proliferation was examined in the CRPC cell line 22Rv1 following individual depletion of mRNAs for the seven genes or shGFP controls, using shRNA against the coding region for each gene (shRNA #2). Cell number was measured using a non-perturbing nuclear restricted dye and quantified after 72 hours using Incucyte Zoom System. Data shown are mean ± s.e.m. of 8 to 12 replicates normalized to their shGFP control. Kruskal-Wallis test (p value < 0.0001, two-tailed) and Dunn's multiple comparisons test were performed.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Representative images of 22Rv1 stably depleted of BUB1B, or control (shGFP) are shown.",
    "ncbi_link": "GFP: 
BUB1B: 701"
  },
  {
    "caption": "22Rv1 stably depleted of each of the seven genes were transfected with a dual plasmid luciferase reporter system which quantifies AR activity and basal transcription. The assay was conducted in 2% CSS to measure AR ligand-independent transcriptional activity. Data represent two independent experiments performed in triplicate, showing the mean ± s.e.m., and normalized to their shGFP controls. Kruskal-Wallis test (p value < 0.0001, two-tailed) and Dunn's multiple comparisons test were performed. * Significant at a p value < 0.05, ** p value < 0.001.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "The expression of FKBP5 and UBE2C determined by RT-qPCR analysis and normalized to GAPDH mRNA levels was examined in 22Rv1 cells stably expressing shRNA for each of the seven genes. Cells were cultured in 2% CSS. Data represent two independent experiments performed in duplicate or triplicate, showing the mean ± s.e.m., and normalized to their shGFP controls. Kruskal-Wallis test (p value < 0.0001, two-tailed) and Dunn's multiple comparisons test were performed. * Significant at a p value < 0.05, ** p value < 0.001.",
    "ncbi_link": "GAPDH: 
GFP: 
FKBP5: 2289
UBE2C: 11065"
  },
  {
    "caption": "The non-tumorigenic prostate epithelial cell line RWPE1, the AR-null PC cell line PC3, the androgen dependent cell line LNCaP, and the CRPC cell lines C4-2B and 22Rv1 were treated for 72 hours with vehicle (DMSO), DOX (100 ng/mL [184 nM]), N-9 (200 ng/mL [613 nM]), or the combination of DOX (100 ng/mL [184 nM]) and N-9 (200 ng/mL [613 nM]). C4-2B and 22Rv1 cells were kept in 10% CSS media, and the other cell lines in 10% FBS. Cell confluence was monitored using the Incucyte Zoom System. Data represent two independent experiments, with four to six replicates each, showing the mean ± s.e.m., and normalized to vehicle controls (Kruskal-Wallis test, P value <0.0001, two-tailed). *Significant at a p value < 0.05, ** p value < 0.01, *** p value < 0.001.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "Immunoblot analysis of p62 and LC3 I/II in KRIT1 wt and KRIT1-KO endothelial cells. Actin was used as a loading control. Quantification of total LC3 on actin is reported (*P = 0.02712). The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Representative images of p62 dots in KRIT1 wt and KRIT1-KO endothelial cells. Scale bar, 20 μm. Magnifications in insets. Right, quantitative analysis of p62 distribution of dots is reported (four independent experiments; n = 35 cells per group). *P = 0.00542 (dotted); *P = 0.00014 (nuclear).",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of p62 and LC3 I/II in KRIT1-KO and KRIT1-KO re-expressing KRIT1 (KO+KRIT1) MEFs. Left, immunoblot showing KRIT1 levels in KRIT1-KO and KO+KRIT1 cells. Right, immunoblots for p62 and LC3 I/II. Actin was used as a loading marker. Quantification of total LC3 on actin is reported (*P = 0.01248). The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Representative images of p62 dots in KO+KRIT1 (top) and KRIT1-KO cells (bottom). Scale bar, 50 μm. Magnifications in insets. Right, quantitative analysis of the number of p62 dots per cell is shown (four independent experiments; n = 50 cells per group). *P = 7.18e−14.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of hBMECs transiently transfected with control siRNA or KRIT1 siRNA. Left, evaluation of siRNA efficiency with antibody directed against KRIT1. Right, immunoblots for p62 and LC3 I/II. Actin was used as a loading marker. Quantification of total LC3 on actin is reported (*P = 0.03071). The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 889"
  },
  {
    "caption": "Immunoblot analysis of EA.hy926 cells transiently transfected with control siRNA or KRIT1 siRNA. Left, evaluation of siRNA efficiency with antibody directed against KRIT1. Right, immunoblot for p62 and LC3 I/II. Actin was used as a loading marker. Quantification of total LC3 on actin is reported (*P = 0.02527). The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 889"
  },
  {
    "caption": "Immunofluorescence analysis of p62 (green) and ProteoStat Aggresome staining detection reagent (red) in KRIT1 wt and KRIT1-KO lung endothelial cells. The yellow signal in the merged images represents an overlapping spatial relationship between green and red fluorescence. Magnification in insets. Scale bar, 50 μm. The images are representative of four independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunofluorescence analysis of p62 (green) and ProteoStat Aggresome staining detection reagent (red) in KRIT1-KO re-expressing KRIT1 (KO+KRIT1) and KRIT1-KO MEFs. The yellow signal in the merged images represents an overlapping spatial relationship between green and red fluorescence. Magnification in insets. Scale bar, 50 μm. The images are representative of four independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis with antibodies directed against phosphorylated mTOR (Ser 2448), total mTOR, phosphorylated p70 S6 Kinase (Ser 371), total p70 S6 Kinase, phosphorylated 4E-BP1 (Thr 37/46), and total 4E-BP1; actin was used as a loading marker. Where indicated, KRIT1 wt and KRIT1-KO endothelial cells were treated with 100 nM Torin1 for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of total ULK1 and actin in KRIT1 wt and KRIT1-KO endothelial cells. Where indicated, cells were treated with 100 nM Torin1 for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of p62, LC3 I/II, and actin in KRIT1 wt and KRIT1-KO endothelial cells treated with 100 nM Torin1 or 500 nM rapamycin for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis with antibodies directed against phosphorylated mTOR (Ser 2448), total mTOR, phosphorylated p70 S6 Kinase (Ser 371), total p70 S6 Kinase, phosphorylated 4E-BP1 (Thr 37/46), and total 4E-BP1; actin was used as a loading marker. Where indicated, KRIT1-KO re-expressing KRIT1 (KO+KRIT1) and KRIT1-KO MEFs were treated with 100 nM Torin1 for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of phosphorylated ULK1 (Ser 757), total ULK1, and actin in KRIT1 KO+KRIT1, and KRIT1 KO MEFs. Where indicated, cells were treated with 100 nM Torin1 for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of p62, actin, LC3 I/II in KO+KRIT1 and KRIT1-KO cells. Where indicated, cells were treated with 100 nM Torin1 for 4 h or 500 nM rapamycin for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "KRIT1 wt and KRIT1-KO endothelial cells were transiently transfected with mRFP-GFP-LC3. Where indicated, the cells were treated with 100 nM Torin1 for 4 h or 2 μM xestospongin B for 4 h. The differences in the autophagic flux were evaluated by counting the yellow LC3 I/II dots/cell (RFP+GFP+) and red LC3 dots/cell (RFP+GFP−) for each condition. Yellow dots: autophagosomes; red dots: autophagolysosomes. *P = 5.74e−5 (red dots, WT ctrl vs. WT Tor1); *P = 9.62e−5 (red dots, WT ctrl vs. WT xesto); *P = 0.00727 (red dots, WT ctrl vs. KO ctrl); #P = 0.00046 (red dots, KO ctrl vs. KO Tor1). The data are expressed as the mean ± s.e.m.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "KO+KRIT1 and KRIT1-KO MEFs were transiently transfected with the mRFP-GFP-LC3 tandem construct. Where indicated, the cells were treated with 100 nM Torin1 for 4 h or 2 μM xestospongin B for 4 h. The differences in the autophagic flux were evaluated by counting the yellow LC3 I/II dots/cell (RFP+GFP+) and red LC3 dots/cell (RFP+GFP−) for each condition. Yellow dots: autophagosomes; red dots: autophagolysosomes. *P = 0.00023 (red dots, KO+KRIT1 ctrl vs. KO+KRIT1 Tor1); *P = 0.00045 (red dots, KO+KRIT1 ctrl vs. KO+KRIT1 xesto); #P = 3.08e−6 (red dots, KO ctrl vs. KO Tor1); ##P = 6.73e−5 (yellow dots, KO+KRIT1 ctrl vs. KO ctrl). The data are expressed as the mean ± s.e.m. of four independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Cd44, PAI1 (also known as Serpine1), and Id1 mRNA expression levels in KRIT1 wt and KRIT1-KO endothelial cells were assessed by quantitative real-time PCR. Where indicated, KRIT1 wt and KRIT1-KO endothelial cells were treated with 100 nM Torin1 or 500 nM rapamycin for 16h. The data are expressed as the mean ± s.e.m. Cd44: *P = 0.02848 (KO ctrl vs. KO Rapa); *P = 0.02605 (KO ctrl vs. KO Tor1). PAI1: *P = 0.04446 (KO ctrl vs. KO Rapa); *P = 0.03996 (KO ctrl vs. KO Tor1). Id1: *P = 0.00266 (KO ctrl vs. KO Rapa); *P = 0.01554 (KO ctrl vs. KO Tor1). n = 3 independent experiments.",
    "ncbi_link": "Cd44: 12505
Id1: 15901
KRIT1: 79264
PAI1: 18787
Serpine1: 18787"
  },
  {
    "caption": "Immunoblot analysis of CD31/Pecam-1, vascular endothelial cadherin (VE-cadherin), and actin in KRIT1-KO endothelial cells that were treated with 100 nM Torin1 or 500 nM rapamycin for 24 h. The results are representative of three independent experiments.",
    "ncbi_link": "KRIT1: 79264"
  },
  {
    "caption": "Immunoblot analysis of CD31/Pecam-1, vascular endothelial cadherin (VE-cadherin), N-cadherin, alpha-smooth muscle actin (alpha-SMA), and actin in HUVECs transfected with control siRNA or ATG7 siRNA.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "Formation of capillary-like structures measured by tube formation assays. HUVECs were transfected with control siRNA or ATG7 siRNA for 72 h. Representative phase-contrast microscopy (Scale bar, 100 μm) and calcein-fluorescent (Scale bar, 50 μm) images were reported. All data are presented as percentage ± s.e.m from three different experiments performed in duplicate. *P = 1.29e−11.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "Immunoblot analysis of p62, LC3I/II, and rapamycin in CCM3 wt and CCM3-KO rapamycin treated with 100 nM Torin1 or 500 nM rapamycin for 4 h. The results are representative of three independent experiments.",
    "ncbi_link": "CCM3: 56426"
  },
  {
    "caption": "Representative immunostaining of retina sections from wt and a model of inducible and endothelial-specific CCM3-KO (CCM3-ECKO) mice at postnatal day 14. Endothelium was stained with isolectin B4 (ISOB4) (blue). A, artery; V, vein. p62 aggregates can be observed in endothelial cells forming retinal lesions in CCM3-ECKO animals (scale bar: 200 μm). Scale bar of magnifications: 100 μm.",
    "ncbi_link": "CCM3: 56426"
  },
  {
    "caption": "Representative immunostaining of brain sections from wt and a model of inducible and endothelial-specific CCM3-knockout mice (CCM3-ECKO) at postnatal day 9. p62 aggregates can be observed in the proximity of CCM lesions (arrows). Cell nuclei (DAPI) are in blue. Scale bar, 30 μm. Smaller panel shows the magnifications of blood vessels (green). Scale bar, 10 μm.",
    "ncbi_link": "CCM3: 56426"
  },
  {
    "caption": "A) Kinetics of S. Typhimurium replication in Tbk1-/- MEFs stably expressing the indicated TBK1 alleles. Intracellular bacteria were enumerated by their ability to form colonies on agar plates following cell lysis at the indicated time points. Statistical analysis comparing Tbk1-/- MEFs and cells expressing TBK1 alleles. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "B) Replication of S. Typhimurium in Atg5-/- MEFs cells complemented with ATG5 or mock and treated with the TBK1 kinase inhibitor MRT68843 (10 nM) or DMSO. Fold replication was determined by counting bacterial colonies on agar plates at 2 and 8 h post inoculation (p.i.) following cell lysis.",
    "ncbi_link": "Atg5: 11793
ATG5: 11793"
  },
  {
    "caption": "C) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium. Percentage of S. Typhimurium coated with ubiquitin (detected by FK2 antibody) at 1 or 4 h p.i. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Percentage of S. Typhimurium coated with GFP:LC3B (A). Where indicated, Wortmannin (Wort) was added at 100 nM.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Percentage of S. Typhimurium coated with the indicated GFP:WIPI alleles (B). Where indicated, Wortmannin (Wort) was added at 100 nM.",
    "ncbi_link": "Tbk1: 56480
TBK1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Confocal microscopy of MEFs expressing the indicated GFP fusion proteins or immunolabeled for WIPI2 and infected with mCherry expressing S. Typhimurium (C-H).",
    "ncbi_link": "Tbk1: 56480
TBK1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Percentage of S. Typhimurium coated with GFP:DFCP1 (FYVE* denotes a PI(3)P-binding mutant of DFCP1) (D-E). Where indicated, Wortmannin (Wort) was added at 100 nM.",
    "ncbi_link": "Tbk1: 56480
DFCP1: 217695"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Confocal microscopy of MEFs expressing the indicated GFP fusion proteins or immunolabeled for WIPI2 and infected with mCherry expressing S. Typhimurium (C-H).",
    "ncbi_link": "TBK1: 56480
Tbk1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Percentage of S. Typhimurium coated with GFP:ML1N*2, a probe for PI(3,5)P2 (G). Where indicated, Wortmannin (Wort) was added at 100 nM.",
    "ncbi_link": "TBK1: 56480
Tbk1: 56480"
  },
  {
    "caption": "A-H) Analysis of Tbk1-/- MEFs stably expressing the indicated TBK1 alleles and infected with S. Typhimurium at 1 h p.i. Confocal microscopy of MEFs expressing the indicated GFP fusion proteins or immunolabeled for WIPI2 and infected with mCherry expressing S. Typhimurium (C-H).",
    "ncbi_link": "TBK1: 56480
Tbk1: 56480"
  },
  {
    "caption": "A-B) Kinetics of S. Typhimurium replication in MEFs depleted of WIPI1 (A). Intracellular bacteria were enumerated by their ability to form colonies on agar plates. Western blot for GFP:WIPI1 upon the indicated siRNA treatments.",
    "ncbi_link": "WIPI1: 52639"
  },
  {
    "caption": "A-B) Kinetics of S. Typhimurium replication in MEFs depleted of WIPI2 (B). Intracellular bacteria were enumerated by their ability to form colonies on agar plates. quantitative RT-PCR for WIPI2 upon the indicated siRNA treatments.",
    "ncbi_link": "WIPI2: 74781"
  },
  {
    "caption": "A-D) Analysis of Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-adaptor fusion proteins. S. Typhimurium replication kinetics (A,D). Infected cells were lysed at the indicated time points post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical significance to Tbk1-/- MEFs expressing TBK1ΔC is indicated. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "A-D) Analysis of Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-adaptor fusion proteins. (B) Percentage of GFP:WIPI1 positive S. Typhimurium at 1 h p.i. in the indicated complemented MEFs. Mean and s.e.m. of four independent experiments. >200 bacteria counted per coverslip. *p<0.05, ***p<0.001, one-way ANOVA with Dunnett's multiple comparisons test.",
    "ncbi_link": "Tbk1: 56480
TBK1: 56480"
  },
  {
    "caption": "A-D) Analysis of Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-adaptor fusion proteins. S. Typhimurium replication kinetics (A,D). Infected cells were lysed at the indicated time points post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical significance to Tbk1-/- MEFs expressing TBK1ΔC is indicated. Western blot for Flag-tagged TBK1 variants in post nuclearcell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "E) Lumier binding assay. Binding of the indicated luciferase-tagged NDP52 variants to beads coated with GST, GST:galectin-8, or GST:ubiquitin. Coomassie stain of purified GST proteins. Western blot for luciferase-tagged NDP52 alleles in total cell lysates.",
    "ncbi_link": "luciferase: 
NDP52: 76815
galectin-8: 56048"
  },
  {
    "caption": "F) Kinetics of S. Typhimurium replication in Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-NDP52 fusion proteins. Infected cells were lysed at the indicated times post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical comparison with Tbk1-/- MEFs expressing TBK1ΔC is indicated. ***p<0.001, one-way ANOVA with Dunnett's multiple comparisons test. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "NDP52: 76815
Tbk1: 56480"
  },
  {
    "caption": "A-B) Analysis of Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-galectin fusion proteins. S. Typhimurium replication kinetics (A). Infected cells were lysed at the indicated times post inoculation (p.i.). and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical differences to Tbk1-/- MEFs expressing TBK1ΔC are shown. *p<0.05, ***p<0.001, one-way ANOVA with Dunnett's multiple comparisons test. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "A-B) Analysis of Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC-galectin fusion proteins. (B) Percentage of GFP:WIPI1 positive S. Typhimurium at 1 h p.i. in the indicated complemented MEFs. Mean and s.e.m. of three independent experiments. >200 bacteria counted per coverslip. *p<0.05, one-way ANOVA with Dunnett's multiple comparisons test.",
    "ncbi_link": "Tbk1: 56480
TBK1: 56480"
  },
  {
    "caption": "B-D) Kinetics of S. Typhimurium replication in Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC fusion proteins. Infected cells were lysed at the indicated time points post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical differences to Tbk1-/- MEFs expressing TBK1ΔC are shown. *p<0.5, **p<0.01, ***p<0.001 one-way ANOVA with Dunnett's multiple comparisons test. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "B-D) Kinetics of S. Typhimurium replication in Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC fusion proteins. Infected cells were lysed at the indicated time points post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical differences to Tbk1-/- MEFs expressing TBK1ΔC are shown. *p<0.5, **p<0.01, ***p<0.001 one-way ANOVA with Dunnett's multiple comparisons test. Western blot for Flag-tagged TBK1 variants in post nuclearcell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "B-D) Kinetics of S. Typhimurium replication in Tbk1-/- MEFs complemented with the indicated Flag-tagged TBK1ΔC fusion proteins. Infected cells were lysed at the indicated time points post inoculation (p.i.) and bacteria were enumerated by their ability to form colonies on agar plates. Mean and s.d. of triplicate MEF cultures and duplicate colony counts. Data are representative of at least two repeats. Statistical differences to Tbk1-/- MEFs expressing TBK1ΔC are shown. *p<0.5, **p<0.01, ***p<0.001 one-way ANOVA with Dunnett's multiple comparisons test. Western blot for Flag-tagged TBK1 variants in post nuclear cell lysates.",
    "ncbi_link": "Tbk1: 56480"
  },
  {
    "caption": "Transcription (bottom) and translation (top) profiles for yggN, rpoH and greA, computed from the RNA-seq and Ribo-seq data without induction. Positions of the genetic parts and gene are shown below the profiles. (C) Promoter strengths in RNAP/s units and RBS initiation rates in ribosome/s units.",
    "ncbi_link": "greA: 947696
rpoH: 947970
yggN: 947453"
  },
  {
    "caption": "Transcription (bottom) and translation (top) profiles for lacZ. Profiles are shown for cells in the absence and presence of IPTG (1 mM). Position of genetic parts and gene is shown below the profiles. RBS is omitted from the genetic design due to its size. (E) Measured promoter strength in RNAP/s units, RBS initiation rate in ribosomes/s units, and the transcriptional terminator and translation termination efficiency for lacZ. Data shown for cells in the absence and presence of IPTG (1 mM).",
    "ncbi_link": "lacZ: "
  },
  {
    "caption": "Translation profiles for the PK-LacZ construct in cells cultured in the absence (bottom) and presence (top) of IPTG (1 mM). The gene10, middle, and lacZ regions are labelled above the profiles. Shaded region denotes the PK, and dashed lines denote the start codon and stop codons of gene10 and LacZ.",
    "ncbi_link": "lacZ: 
LacZ: "
  },
  {
    "caption": "Fraction of the total RPFs and mRNA reads in each reading frame for the gene10, PK or middle, and lacZ regions schematically shown below and are of the PK-LacZ construct. Data shown separately for cells cultured in the absence and presence of IPTG (1 mM).",
    "ncbi_link": "lacZ: 
LacZ: "
  },
  {
    "caption": "Change in expression of chromosomal genes in E. coli cells following induction of PK-lacZ expression (1 mM IPTG). Each point represents a transcript. Differentially expressed genes (mRNA count: P < 0.001 and absolute log2 fold-change > 1.37; translation efficiency: P < 0.01) are highlighted in color and by an alternative point shape (transcriptional regulation: purple cross; translational regulation: orange open circle).",
    "ncbi_link": "lacZ: "
  },
  {
    "caption": "Translation initiation rates for all E. coli RBSs in cells harboring the LacZ and PK-LacZ constructs in the absence and presence of IPTG (1 mM). Solid line shows the same initiation rate for both conditions. Dotted lines denote linear regressions for the data with no offset.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "Fractions of mRNA reads and RPFs mapping to each synthetic expression construct (LacZ and PK-LacZ) and E. coli transcripts, which are divided into three major categories: ribosomal, metabolic, and other functions. Data shown for cells cultured in the absence and presence of IPTG (1 mM).",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "(A) Quantitative analysis of Rnf114 mRNA by realtime-PCR in various mouse tissues and organs shows that Rnf114 was predominately expressed in oocytes.",
    "ncbi_link": "Rnf114: 81018"
  },
  {
    "caption": "(C) Knockdown efficiency of Rnf114 in the 2-cell stage embryos derived from Rnf114 siRNA #1 or siRNA #2 injected zygotes was verified by realtime-PCR and western blotting. NC indicates negative control injected with non-silencing siRNA. Three independent experiment replicates were performed for realtime-PCR, error bars represent s.e.m.; **:P<0.01, ***:P<0.01 in unpaired two-tailed t-test.",
    "ncbi_link": "Rnf114: 81018"
  },
  {
    "caption": "(D) RNF114 depletion impaired the early embryonic development. Rnf114 siRNA #1 or siRNA #2 injected zygotes were cultured and quantified (siRNA1#, n = 120; siRNA2#, n = 128; three independent experiments); NC indicates negative control (n = 193; six independent experiments). The error bars represent s.d., *:P<0.05, **:P<0.01, ***:P<0.001 in unpaired two-tailed t-test.",
    "ncbi_link": "Rnf114: 81018
RNF114: 81018"
  },
  {
    "caption": "(B, C) Purified wild-type and RING mutated His-RNF114 were stained by Coomassie Blue (B). Purified wild-type and RING mutated His-RNF114 were subjected to ubiquitination assays together with E1, Ubc4, FLAG-Ub, and ATP. The results show that mutant RNF114 lacked ubiquitination activity (C).",
    "ncbi_link": "RNF114: 81018"
  },
  {
    "caption": "(D) Screening for proteins ubiquitinated by RNF114 on a proteome array. Putative substrates of RNF114 were identified on Ubiquitin Ligase Substrate Identification on ProtoArray® Human Protein Microarrays v5.0. Ubiquitination reactions were performed on quintuplicate arrays using the indicated components, the five sub-array are respectively negative controls, E1+E2 (no E3), WT RNF114 (two arrays, duplicate), and mutated RNF114.",
    "ncbi_link": "RNF114: 55905"
  },
  {
    "caption": "(E) A heat map comparing hits between E1+E2, E1+E2+WT RNF114, and E1+E2+mutated RNF114 reactions. Candidate substrates of RNF114 selected for further characterization are indicated in red font; HIP1, indicated by blue font, was considered to be a false positive because it was also detected in the mutated RNF114 reaction. Black font indicates proteins with ubiquitin-binding domains such as UIM, UBA or CUE or proteins without clearly reported functions, which were excluded from further investigation.",
    "ncbi_link": "RNF114: 55905"
  },
  {
    "caption": "(A) RNF114 substrate validation. HEK293 cells were co-transfected with constructs expressing FLAG-tagged substrates, wild-type or mutated His-RNF114 and EGFP, and western blot was performed with anti-FLAG and anti-His antibodies. The results show that the protein levels of CD74, TAB1, OPTN, TNIP1, APPL1, PSAT1, and RALGPS1 were reduced in the presence of wild-type RNF114 compared to co-transfecting with mutant RNF114.",
    "ncbi_link": "RNF114: 55905"
  },
  {
    "caption": "(B) RNF114-dependent in vitro ubiquitination of substrates. Substrate ubiquitination assays were performed with purified RNF114, the reaction products were immunoblotted using anti-His antibody to detect the ubiquitin (upper panel) or anti-FLAG antibody detecting the substrate protein (middle panel), and the lower panel showed the merged signals. The results show that clear polyubiquitin chains were formed in the systems containing recombinant CD74, TAB1, TNIP1, PSAT1 or RALGPS1.",
    "ncbi_link": "RNF114: 55905"
  },
  {
    "caption": "(A) Mouse zygotes were microinjected with sterile ddH2O (control group) or Ralgps1, Cd74, Tnip1, Psat1, or Tab1 mRNA. During 96-100 h culturing, the percentages of embryos at various stages were counted under microscopy. The results show that overexpression of Tab1 impaired the early embryonic development. Three independent experiment replicates were performed, error bars represent s.d.; *:P<0.05, ***:P<0.001 in unpaired two-tailed t-test.",
    "ncbi_link": "Cd74: 16149
Psat1: 107272
Ralgps1: 241308
Tab1: 66513
Tnip1: 57783"
  },
  {
    "caption": "(B) TAB1 reduced with mouse early embryonic development, while abnormally accumulated at 2-cell stage once treated with Rnf114 siRNAs. TAB1 was detected by western blotting with anti-TAB1 antibody. The relative level of TAB1 protein after Rnf114 siRNAs treatment were presented as mean±s.e.m. (*:P<0.05 in unpaired two-tailed t-test, four independent experiment replicates).",
    "ncbi_link": "Rnf114: 81018"
  },
  {
    "caption": "(D) RNF114-dependent TAB1 degradation during early embryo development. (a-c) Representive time lapse embryo images were shown for each treatment. Scale bar = 20um. (a'-c') Quantification of the GFP fluorescent signals for respective treatments in (a-c). n=14, 9 or 12 for the NC, Rnf114 siRNA1# or Rnf114 siRNA2# treatment group respectively. Gray traces: Tab1-GFP fluorescent signals were normalized to the first time point; Black trace: average signal of all embryos for each treatment.",
    "ncbi_link": "Rnf114: 81018
RNF114: 81018"
  },
  {
    "caption": "(E) Tab1 knockdown partly rescued the early embryo development defect observed with Rnf114 knockdown. Both Rnf114 and Tab1 siRNAs were injected into the GV oocytes, then the oocytes matured, and were fertilized by IVF, and the fertilized eggs were transferred into KSOM media, cultured for 48-50 h. The percentages of embryos arrested at 2-cell stage were counted. Three independent experiment replicates were performed, error bars represent s.d.; **:P<0.01 in unpaired two-tailed t-test.",
    "ncbi_link": "Rnf114: 81018
Tab1: 66513"
  },
  {
    "caption": "(D, E) Representive immunofluorescence staining of p65 after knockdown of Rnf114 by Rnf114 siRNA #1 or siRNA #2 or overexpression of Tab1 by Tab1 mRNA injection (shown in D. Scale bar = 25um.), the percentages of two-cell stage embryos with p65 nuclear translocation (shown in E.) were significantly decreased after Rnf114 knockdown or Tab1 overexpression (chi-square test was performed for statistical analysis).",
    "ncbi_link": "Rnf114: 81018
Tab1: 66513"
  },
  {
    "caption": "(F) Western blot analysis at 2-cell stage showed the levels of p-IκBα were downregulated in the Rnf114 siRNA #1, siRNA #2 injected groups.",
    "ncbi_link": "Rnf114: 81018"
  },
  {
    "caption": "(G) Western blot analysis at 2-cell stage showed the levels of p-IκBα were downregulated in the exogenous Tab1 mRNA injected groups, ddH2O was injected as control. Dotted line indicates a cropped lane.",
    "ncbi_link": "Tab1: 66513"
  },
  {
    "caption": "B | hFwe-Lose mRNA expression is more abundant in elderly people. hFwe-Lose mRNA expression was analyzed by RT-qPCR in 86 lung tissue biopsies taken from non-COVID patients with age between 20 and 82 years. Older patients show a significant upregulation of hFwe-Lose expression. A log-Linear regression model demonstrates a positive correlation between age and hFwe-Lose expression (R2= 0.13; slope confidence interval of 95% (CI) = [2.0-12.2]; p-value of the linear regression model < 6⋅10-4).",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "C | hFwe-Lose expression is elevated in lung tissue biopsies from patients with comorbidities. Box plot illustrates an increased expression of hFwe-Lose in lungs of patients with hypertension (HT; n = 129), obesity (n = 45), chronic obstructive pulmonary disease (COPD n = 51), diabetes (n = 48), cardio-vascular disease (CVD; n = 63) versus disease-free control lungs (n = 42). Patient`s age is depicted in color. Two-sided Student's t-test was performed for each comorbidity (compared to disease-free patients), and p-values are presented on the plot. The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "D | hFwe-Lose expression is upregulated in lung tissue of COVID-19 patients. Box plot illustrates an increased expression of hFwe-Lose in lung tissue of patients diagnosed with COVID-19 (n = 11), individuals affected with host comorbidities (n = 216) versus disease-free control lungs (n = 42). Patient's age is depicted in color. Two-sided Student's t-test was performed (compared to disease-free patients), and p-values are presented on the plot. The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "A | hFwe-Lose biomarker expression is more abundant in nasopharyngeal swab probes from older adults. hFwe-Lose expression was analyzed by RT-qPCR in 283 nasopharyngeal swab samples taken from patients with age between 1 and 96 years, taken at the very beginning of the disease (the earliest contact with physician, before the disease progression). The vertical axis represents relative hFwe-Lose expression normalized to the mean of non-hospitalized patients. Colors depict the outcome groups: non-hospitalized (gray, n = 85), hospitalized (blue, n = 177) and deceased (red, n = 21). The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The lines show the fitted curves of an asymptotic model with the same asymptotic value but different rate constants per group (see Materials and Methods). Due to the comparatively low number of deceased patients in the dataset (n = 21), the curve for this group reflects the asymptotic value. Hospitalized and deceased patients show a positive correlation of hFwe-Lose expression and age with a larger rate constant for the hospitalized patients. (R2= 0.65) The p-value (< 0.001) indicates that the blue curve (for hospitalized patients) grows faster with age, compared to the gray curve for non-hospitalized patients).",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "B | hFwe-Lose expression is elevated in nasopharyngeal swab probes from patients with comorbidities. Box plots illustrate an increased relative expression of hFwe-Lose in nasopharyngeal swabs of patients with diabetes (n = 129), COPD (n = 20), obesity (BMI > 30; n = 152), cardiomyopathy ("CM", n = 19), heart failure ("HF", n = 35), hypertension ("HT", n = 121), chronic kidney disease ("CKD", n = 60) versus disease-free patients (n = 96). Two-sided Student's t-tests were performed (compared to disease-free patients), and p-values are presented on the plot. The vertical axis represents relative hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "D | Elevated hFwe-Lose expression in the nasal swab samples associates with patients' condition severity and respective medical treatment. Box plots illustrate an increased expression of hFwe-Lose in nasal swabs of patients, who were hospitalized within 14 days of disease progression (n = 177), admitted to intensive care unit (ICU) (n = 34), underwent intubation (n = 58), had respiratory rate greater than 30 (GT30) (n = 76), had blood oxygenation level (SpO2) less than 94% (n = 147), and who died within 30 days of disease progression (n = 21) versus patients without respective conditions. Pairwise two-sided Student's t-tests were performed (compared to patients without respective conditions), and p-values are presented on the plot. The vertical axis represents hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "E |Elevated hFwe-Lose expression in nasal swab associates with patients' disease outcome. Box plot emphasizes an increased expression of hFwe-Lose in nasal swabs of patients, who were hospitalized within 14 days of disease progression (n = 177), and who died within 30 days of disease progression (n = 21) versus patients without respective conditions. Two-sided Student's t-tests were performed (compared to non-hospitalised patients), and p-values are presented on the plot. The vertical axis represents hFwe-Lose expression normalized to the mean of non-hospitalized patients. The color refers to the COVID-19 disease outcome: gray for not hospitalised, blue for hospitalised and red for deceased patients. The shape of data points reflects the cohorts: circles for the training cohort (n = 203) and triangles for the validation cohort (n = 80). The central band shows the median, the box indicates the interquartile range, the whiskers extend to the most extreme points within the 1.5-fold distance of the interquartile range above and below the box.",
    "ncbi_link": "hFwe-Lose: "
  },
  {
    "caption": "(A-D)  Chip-seq  genome track of ASCL1/NEUROD1, RNAPII, and H3K27Ac on ASCL1, BCL2; INSM1  and MYB (hg19), in untreated (dark blue) and in lurbinectedin treated (green) conditions respectively; to be noticed the location of CGG rich motifs (lower part of each panel) which parallel the presence of lurbinectedin (red).",
    "ncbi_link": "ASCL1: 429
BCL2: 596
INSM1: 3642
MYB: 4602"
  },
  {
    "caption": "(A) LncRNA CRNDE expression level was measured by qRT-PCR  in cancerous  tissues  and adjacent normal tissues obtained from 35 cases of gastric cancer  (GC) patients. Data information: Data are expressed as mean ± SD. Student's t-test **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "(C) LncRNA CRNDE expression level was measured by qRT-PCR in adjacent normal tissue-derived  macrophages (NTMs) and tumor-associated macrophages (TAMs) obtained from 7 cases of GC patients. Data information: Data are expressed as mean ± SD. Student's t-test **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "(C) and (D) Left: representative  electron micrograph of exosomes  isolated from the medium of BMDMs,  BMDM-polarized  M2 macrophages, monocytes and  monocyte-polarized  M2 macrophages are depicted, showing the typical morphology  of exosomes. Upper right: the protein levels of CD63  and CD81  were measured by Western blot. Lower left: Nanoparticle tracking analysis showed that most of the particles had a similar size of 50-150 nm in diameter with a peak at around 100 nm. Lower right: LncRNA CRNDE expression levels in different exosomes. Data information: Scale bar= 100 nm. The results shown are from three biological replicates. Data are expressed as mean ± SD. Student's t-test. **P<0.01 vs. BMDMs or monocytes  or BMDMs-exo or monocytes-exo. ",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "(B)  BMDM-polarized M2 macrophages  were transfected with Cy3-labelled CRNDE and  exosomes were isolated from the medium (Cy3-CRNDE-EXO). Then, MFC  cells were incubated with Cy3-CRNDE-EXO. Left: Confocal microscopy was used to detect the  Cy3-labelled  CRNDE in MFC cells. The  nuclei were  stained  with DAPI. Scale bar= 20 µm. Right: Flow cytometry was performed to quantitate the Cy3-positive cells. **P<0.01 vs. MFC cells incubated with the control  EXO. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. Student's t-test.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "(D) Monocyte-polarized  M2 macrophages were transfected with Cy3-labelled  CRNDE  and  exosomes  were isolated from the medium (Cy3-CRNDE-EXO). Then, SGC7901 cells were incubated with  Cy3-CRNDE-EXO. Confocal microscopy  was used to detect the  Cy3-labelled CRNDE in SGC7901 cells. The  nuclei were stained  with DAPI. Scale bar= 20 µm. Right: Flow cytometry was performed to quantitate the Cy3-positive cells. **P<0.01 vs. SGC7901 cells incubated with the control  EXO. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. Student's t-test.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "(E) SGC7901  cells were incubated with chlorpromazine (CPZ, 50 μM),  genistein (GEN, 200 μM), 5-(n-ethyl-n-isopropyl)-amiloride (EIPA, 100 μM), or methyl-β-cyclodextrin (MβCD, 10 mM), following by the incubation of Cy3-CRNDE-EXO.  Confocal microscopy was used to detect the  Cy3-labelled  CRNDE in SGC7901  cells. The nuclei were stained with  DAPI. Right: Flow cytometry was performed to quantitate the Cy3-positive cells. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "(F) SGC7901 cells were incubated with 0, 25, 50, 100 μM CPZ, following by the incubation of  Cy3-CRNDE-EXO.  Confocal microscopy was used to detect the Cy3-labelled  CRNDE  in SGC7901 cells. The nuclei were  stained with DAPI. Right: Flow cytometry  was performed to quantitate the Cy3-positive cells. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "Exosomes were isolated from the media of  BMDMs  (BMDMs-exo), BMDM-polarized M2 macrophages  (M2-exo), BMDM-polarized  M2 macrophages transfected with si-CRNDE (M2-si-CRNDE-exo), and BMDM-polarized M2 macrophages transfected with the negative control of si-CRNDE (M2-si-control-exo). (A) LncRNA CRNDE expression in indicated exosomes was detected by qRT-PCR. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. : one-way ANOVA. **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "Exosomes were isolated from the media of BMDMs (BMDMs-exo), BMDM-polarized  M2 macrophages (M2-exo), BMDM-polarized M2 macrophages transfected with si-CRNDE (M2-si-CRNDE-exo), and BMDM-polarized M2 macrophages transfected with the negative control of si-CRNDE (M2-si-control-exo). Then, MFC cells were treated with indicated exosomes  and cisplatin (CDDP; 1μg/ml) for 48 h. (C) Representative images of colony formation assay performed on MFC cells.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "Exosomes  were isolated from the medium of monocytes (monocytes-exo), monocyte-polarized M2 macrophages (M2-exo), monocyte-polarized M2 macrophages transfected with si-CRNDE (M2-si-CRNDE-exo), and monocyte-polarized M2 macrophages transfected with si-control (M2-si-control-exo). (E) LncRNA CRNDE expression were measured. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA. **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "Exosomes were isolated from the medium of monocytes (monocytes-exo), monocyte-polarized M2 macrophages  (M2-exo), monocyte-polarized M2 macrophages transfected with si-CRNDE (M2-si-CRNDE-exo), and  monocyte-polarized M2 macrophages transfected with si-control (M2-si-control-exo). Then, SGC7901 cells were treated with indicated exosomes and CDDP (1μg/ml). (G) cell proliferation  were measured.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "3×105 MFC cells were subcutaneously injected into nude mice. Ten days after injection, BMDMs-exo, M2-exo, M2-si-control-exo, or  M2-si-CRNDE-exo (10 µg) was injected into the center of the homograft tumors of mice (n=7 each group), followed by intraperitoneal injection of CDDP (10 mg/kg). Six days after CDDP treatment, all mice were sacrificed and the homograft tumors were collected. (A) Growth curves of MFC  subcutaneous homograft tumors (The homograft tumor sizes were recorded from the day of CDDP  treatment). *P<0.05, **P<0.01 vs. BMDMs-exo; #P<0.05, ##P<0.01 vs. M2-si-control-exo. Data information: Data are expressed as mean ± SD. one-way ANOVA.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "3×105 MFC cells were subcutaneously injected into nude mice. Ten days after injection, BMDMs-exo, M2-exo, M2-si-control-exo, or M2-si-CRNDE-exo (10 µg) was injected into the center of the homograft tumors of  mice  (n=7 each group), followed by intraperitoneal injection of CDDP (10 mg/kg). Six days after CDDP treatment, all mice  were sacrificed and the homograft tumors were collected. (D) LncRNA CRNDE expression in homograft tumors of  mice. **P<0.01. Data information: Data are expressed as mean ± SD. : one-way ANOVA.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "(C) SGC7901 cells were transfected with pcDNA-CRNDE or its negative control (Mock) before MG132 treatment (10 µM, 6 h). The Co-immunoprecipitation (Co-IP) assay was performed to examine the combination of PTEN and NEDD4-1.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "(E) The  expressions of PTEN and  NEDD4-1 were measured in SGC7901 cells transfected with pcDNA-CRNDE or Mock at four time-points after cycloheximide (CHX, 100 μg/mL) treatment. GAPDH  was served as an internal control. Left: Representative bands. Right: Quantitative results. The results shown are from three biological replicates and are expressed as mean ± SD. Student's t-test. *P<0.05, **P<0.01 vs. Mock.",
    "ncbi_link": "CRNDE: "
  },
  {
    "caption": "Normal, si-control-transfected, or si-PTEN-transfected  SGC7901 cells were treated with CDDP (1 µg/ml) and M2-si-control-exo or M2-si-CRNDE-exo. Si-control, the negative control of si-PTEN. (A) The protein levels of  PTEN, phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), p-glycoprotein (p-gp), B-cell lymphoma 2 (Bcl-2) were measured. GAPDH was served as an internal control.",
    "ncbi_link": "CRNDE: 643911
PTEN: 5728"
  },
  {
    "caption": "Normal, si-control-transfected, or si-PTEN-transfected  SGC7901 cells were treated with CDDP  (1 µg/ml) and M2-si-control-exo or M2-si-CRNDE-exo. Si-control, the negative control of si-PTEN. The cell apoptosis in SGC7901  cells. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA. **P<0.01.",
    "ncbi_link": "CRNDE: 643911
PTEN: 5728"
  },
  {
    "caption": "SGC7901  cells were divided into four groups: M2-si-control-exo, M2-si-CRNDE-exo, M2-si-CRNDE-exo +PTEN inhibitor (SF1670; 50 μmol/l), M2-si-control-exo+PTEN inhibitor. All cells were treated with  CDDP. The cell survival rate were measured. Data information: The results shown are from seven biological replicates. Data are expressed as mean ± SD. : one-way ANOVA. **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "SGC7901 cells were divided into four groups: M2-si-control-exo,  M2-si-CRNDE-exo, M2-si-CRNDE-exo +PTEN inhibitor (SF1670; 50 μmol/l), M2-si-control-exo+PTEN inhibitor. All cells were treated with CDDP. The cell apoptosis were measured. Data information: The results shown are from three biological replicates. Data are expressed as mean ± SD. one-way ANOVA. **P<0.01.",
    "ncbi_link": "CRNDE: 643911"
  },
  {
    "caption": "C. As for A, but analysing Col/Ler SNPs/kb around crossovers from wild type, HEI10-OE, recq4a recq4b or HEI10-OE recq4a recq4b (Serra et al, 2018b). All populations were generated from Col×Ler hybrids. Printed beneath are the estimated average numbers of Class I and Class II crossovers per meiosis for each genotype, measured via genotyping-by-sequencing (Serra et al, 2018b; Ziolkowski et al, 2017). To the right are plots showing the significance of SNPs/kb differences between crossover sets, across the windows tested (Bonferroni adjusted t-tests).",
    "ncbi_link": "HEI10: 841784
recq4a: 837636
recq4b: 842384"
  },
  {
    "caption": "A. Histograms of observed crossovers per F2 individual in the indicated wild type and msh2 populations, from Col×Ct, Col×Ler and Col×CLC crosses (blue). The Poisson expectation is plotted in red. Data from HEI10-OE, recq4a recq4b and HEI10-OE recq4a recq4b F2 populations are also shown for comparison (Serra et al, 2018b; Ziolkowski et al, 2017). Mean values are indicated by black dotted lines.",
    "ncbi_link": "HEI10: 841784
msh2: 821383
recq4a: 837636
recq4b: 842384"
  },
  {
    "caption": "B. Crossovers per 200 kb per F2 plotted along the Arabidopsis chromosomes, with mean values shown by horizontal dashed lines. Data are shown for wild type (red) and msh2 (blue) crossovers generated from Col×Ct, Col×Ler and Col×CLC hybrids. SNPs per 200 kb are shaded in colour (blue=Col/Ct, green=Col/Ler, pink=Col/Cvi). The positions of telomeres (TEL) and centromeres (CEN) are labeled. The number of crossovers analysed is printed inset. C. Data as for B, but analyzing crossovers in wild type (red) and msh2 (blue), or SNPs along proportionally scaled chromosome arms orientated from telomeres (TEL) to centromeres (CEN). Crossover data from HEI10-OE, recq4a recq4b and HEI10-OE recq4a recq4b Col×Ler F2 populations are also shown (Serra et al, 2018b; Ziolkowski et al, 2017).",
    "ncbi_link": "HEI10: 
HEI10: 841784
msh2: 821383
recq4a: 837636
recq4b: 842384"
  },
  {
    "caption": "B. SNPs/kb values were calculated in physical windows of increasing size (kb) around crossover midpoints in wild type (red) and msh2 (blue). The same values were calculated for matched randomly chosen positions (grey). Printed above the plot for each window are circles that are coloured green if crossover SNPs/kb values are significantly different to random (P<0.05), or red if not (P>0.05) (Bonferroni adjusted t-tests). The population analysed (Col×Ct, Col×Ler, Col×CLC) and its genome average SNP frequency (SNPs/kb) is printed above the plots and the number of crossover positions analysed is printed inset. Beneath are plots showing the significance of SNPs/kb differences around crossovers between the indicated genotypes.",
    "ncbi_link": "msh2: 821383"
  },
  {
    "caption": "A. Representative DAPI-stained spreads of pachytene, diakinesis, metaphase-I, dyad and tetrad meiotic stages, for wild type and msh2, in Col×Ler or Col×CLC hybrid backgrounds.",
    "ncbi_link": "msh2: 821383"
  },
  {
    "caption": "B. Male meiocytes immunostained for MSH2 (red) and ASY1 (green), and stained for DAPI (blue) in wild type (Col) or msh2.",
    "ncbi_link": "msh2: 821383"
  },
  {
    "caption": "C. 420 crossover frequency (cM) in the HOM-HOM, HET-HET, HET-HOM, HOM-HET genotypes shown in B, in either wild type or msh2. Values for replicate individuals are plotted, in addition to the mean (red).",
    "ncbi_link": "msh2: 821383"
  },
  {
    "caption": "D. As for C, but comparing genotypes in wild type or HEI10-OE backgrounds. Values for replicate individuals are plotted, in addition to the mean (red).",
    "ncbi_link": "HEI10: 841784"
  },
  {
    "caption": "(H) The  bur1-ΔC mutant exhibits a synthetic growth defect with the  vac17Δ mutant. Plasmids were transformed into a bur1Δ or  bur1Δ vac17Δ mutant containing YCp50 [URA3] BUR1. Plasmids tested were pRS415 [LEU2] (mock), pRS415 BUR1, or pRS415 bur1-ΔC. Transformed colonies were cultured in liquid medium and serial dilutions spotted onto SC+5-FOA or SC-Leu-Ura  plates. Plates were incubated at 24 ̊C for 3 days.",
    "ncbi_link": "LEU2: 850342
bur1: 856290
BUR1: 856290
URA3: 856692
vac17: 850296"
  },
  {
    "caption": "(A, B) The  bur1-ΔC  vac17Δ double mutant exhibits a delay in progression  through  G1  phase of the cell cycle. Yeast were grown in  YPD  medium and collected in log phase growth. DNA content was measured using propidium iodide (PI) staining  and assessed by  flow cytometry. p-value determined with a one-way ANOVA and Tukey post hoc test. ** (p-value < 1 x 10-2). Error bars; SD calculated from at least four independent experiments with at least 100 cells counted in each strain/experiment. (C, D) A bur1-267 mutant also exhibits a delay in progression through  G1  phase of the  cell cycle. DNA content was measured using   PI staining and assessed by flow cytometry. p-value determined with a one-way ANOVA and Tukey post hoc test. **** (p-value < 1 x 10-4). Error bars; SD calculated from at least four independent experiments with at least 100 cells counted in each strain/experiment.",
    "ncbi_link": "bur1: 856290
vac17: 850296"
  },
  {
    "caption": "(E, F) The bur1-ΔC  vac17Δ double mutant shows accumulation of Whi5 in the nucleus. WT, vac17Δ, bur1-ΔC, and bur1-ΔC vac17Δ cells, which express Whi5-3xGFP and  Nup188-mCherry from endogenous loci, were incubated at 24 ̊C. Cells were scored for the presence of Whi5-3xGFP in within the nucleus (Nup188-mCherry). Error bars; SD calculated from at least four independent experiments with at least 100 cells counted in each strain/experiment. p-value determined with a one-way ANOVA and Tukey post hoc test. ** (p-value < 1 x 10-2). Error bars; SD calculated from at least four independent experiments with at least 100 cells counted in each strain/experiment. Scale bar, 2 μm.",
    "ncbi_link": "bur1: 856290
vac17: 850296"
  },
  {
    "caption": "(B) The bur1-∆C vac17∆ double mutant cells have the ability to generate a  vacuole de novo, which suggests that the  cell-cycle delay is due to a defect in Bur1-dependent signaling. WT, vac17Δ, bur1-∆C, and bur1-∆C vac17∆ cells which express  Vph1-GFP from its endogenous locus, were  pulse labeled with the  vacuole specific dye FM4-64. WT and bur1-∆C cells have both FM4-64 and Vph1-GFP  signals in both mother and daughter cells. vac17Δ and bur1-∆C vac17∆ cells have both  Vph1-GFP  and  FM4-64 on the vacuole in mother cells, however the daughter cells solely have a Vph1-GFP labeled vacuole, indicating that the vacuole was generated de novo, rather than inherited from the mother vacuole. Arrowheads; new vacuoles in daughter cells. Scale bar, 2 μm.",
    "ncbi_link": "bur1: 856290
Bur1: 856290
vac17: 850296"
  },
  {
    "caption": "(A) In vivo phosphorylation  of Sch9  is reduced in  bur1-∆C vac17∆ cells. WT, bur1-∆C, vac17∆, or  bur1-∆C vac17∆ cells expressing SCH9-HA from the URA3 locus were grown in  YPD. Cell lysates were analyzed by immunoblot  with antibodies directed against  HA (top) and Pgk1 (loading control). (B) In vivo phosphorylation of Sch9 is reduced in bur1-267 cells. WT, vac17∆, bur1-267, or  bur1-267 vac17∆ cells expressing SCH9-HA from the URA3  locus were grown in  YPD. Cell lysates were analyzed by immunoblot with antibodies directed against  HA (top) and Pgk1  (loading control).",
    "ncbi_link": "bur1: 856290
URA3: 856692
vac17: 850296"
  },
  {
    "caption": "(C) bur1-∆C shows high rapamycin sensitivity. WT, tor1∆, bur1-∆C,  tor1∆ bur1-∆C or vac17∆ cells were cultured in liquid YPD medium and serial dilutions were spotted onto YPD plates with 0, 2, 4 or 8 ng/ml of  rapamycin added. Plates were incubated at 24 ̊C for 2 days.",
    "ncbi_link": "bur1: 856290
tor1: 853529
vac17: 850296"
  },
  {
    "caption": "(B) In vitro, Bur1 directly phosphorylates the kinase domain of Sch9 as well as Bur1  itself. pRS425 BUR1-HA and pVT102-Ura BUR2, the essential cyclin for BUR1, were co-expressed in a bur1Δ mutant, immunoprecipitated using anti-HA antibody and protein A  beads, and then incubated with [γ-32P]ATP  and GST, GST-N-Sch9  (1-390) or GST-C-Sch9  (391-824). Proteins were eluted with SDS  sample buffer, separated by  SDS-PAGE, and transferred to  nitrocellulose  membranes. Membranes exposed to x-ray film (top) or stained  with Ponceau S (bottom). Red arrowhead; phosphorylated GST-C-Sch9. Gray arrowhead; auto-phosphorylated Bur1.",
    "ncbi_link": "HA: 
BUR2: 850923
BUR1: 856290
bur1: 856290"
  },
  {
    "caption": "(D)  Sch9-2D3E, but not Sch9-3A-2D3E, partially suppressed the rapamycin sensitivity of tor1∆ cells.  tor1∆ which expresses pRS426 (mock), pRS425 TOR1, pVT102-Ura (mock), pVT102-Ura Sch9, pVT102-Ura Sch9-2D3E, or pVT102-Ura Sch9-3A-2D3E, were cultured in liquid SC-Ura  medium and serial dilutions spotted onto SC-Ura plates with 0 or 8 ng/ml of rapamycin added. Plates were incubated at 24 ̊C for 2-3 days.",
    "ncbi_link": "Sch9: 856612
tor1: 853529
TOR1: 853529"
  },
  {
    "caption": "(E) The  Sch9-2D3E mutant did not suppress the rapamycin sensitivity of bur1-∆C cells. bur1-∆C which expresses pRS426 (mock), pRS426 BUR1, pVT102-Ura (mock), pVT102-Ura SCH9, pVT102-Ura sch9-2D3E, pVT102-Ura sch9-3A-2D3E, pVT102-Ura sch9-3D/E, or pVT102-Ura sch9-3D/E-2D3E were cultured in liquid  SC-Ura medium and serial dilutions spotted onto  SC-Ura plates with 0 or 8 ng/ml of  rapamycin  added. Plates were incubated at 24 ̊C for 3 days.",
    "ncbi_link": "sch9: 856612
Sch9: 856612
SCH9: 856612
bur1: 856290
BUR1: 856290"
  },
  {
    "caption": "(A) Bur1  fused SV40-NLS does not rescue the rapamycin sensitivity of bur1-∆C compared to Bur1 without the NLS. bur1-∆C which expresses pRS416 (mock), pRS416 BUR1, pRS416 BUR1-mNG, pRS416 BUR1-mNG-NLS, pRS416 bur1-∆C, pRS416  bur1-∆C-mNG-NLS or pRS416 bur1-∆N, were cultured in liquid SC-Ura medium and serial dilutions spotted onto SC-Ura plates with 0, 4, 8, or 16 ng/ml of rapamycin added. Plates were incubated at 24 ̊C for 2 days.",
    "ncbi_link": "mNG: 
bur1: 856290
Bur1: 856290
BUR1: 856290"
  },
  {
    "caption": "(B) Adding nuclear-export signal (NES) of PKI to Bur1 and/or deletion of the   importin α-dependent NLS  from  Bur1  resulted in higher sensitivity to rapamycin compared to Bur1  without this NES. bur1-∆C which expresses pRS426 (mock), pRS426 BUR1, pRS426 bur1-∆N, pRS426  BUR1-mNG, pRS426 BUR1-mNG-NES, or pRS426 bur1-∆N-mNG-NES, were cultured in liquid  SC-Ura medium and serial dilutions spotted onto SC-Ura plates with 0, 4, 8, or 16 ng/ml of  rapamycin added. Plates were incubated at 24 ̊C for 2 days.",
    "ncbi_link": "mNG: 
BUR1: 856290
Bur1: 856290
bur1: 856290"
  },
  {
    "caption": "Representative flow cytometric showing the specific depletion efficiency of ATM subsets from eWAT of CD169-DTR ND- (A) or HFD-treated (16 weeks) (B) mice. A representative analysis of three independent experiments is shown.",
    "ncbi_link": "DTR: 15200
CD169: 20612"
  },
  {
    "caption": "eWAT was collected from lean (C) and obese (HFD 16 weeks) (D) WT or CD169-DTR mice after 12 days DT-mediated ATM depletion. Representative pictures of dissected eWAT are shown on the left, the corresponding eWAT weights expressed as mean ± SD of more than 12 samples are shown in the right, with statistical significance calculated using the Student's t-test (**P < 0.01 and ****P < 0.0001). The zoomed-in area shows clear, oily lipid accumulation in the absence of ATMs (lower left part).",
    "ncbi_link": "DTR: 15200
CD169: 20612"
  },
  {
    "caption": "Adipocyte hypertrophy is visible in the absence of ATMs. Representative images of hematoxylin and eosin staining (H&E) (E) and corresponding adipocyte diameters (F) of lean and obese (HFD 16 weeks) eWAT from WT or CD169-DTR mice treated for 7 or 12 days with DT. Scale bar, 50 μm. Each group comprised 3-5 mice. Statistical significance was determined using one-way ANOVA test. **P < 0.01; ****P < 0.0001; ns: no significant difference. The box and whisker plots show the median value and 10-90 percentiles of adipocyte diameters.",
    "ncbi_link": "DTR: 15200
CD169: 20612"
  },
  {
    "caption": "qPCR showing the relative expression of genes for adipogenesis (Pparγ), lipolysis (Lpl), and lipogenesis (Dgat1), plus other lipid receptor/transporters (Cd36, Abca1) or chaperones (Fabp4) in obese (HFD 16 weeks) eWAT of CD169-DTR (red bars) mice and DT-injected WT controls (blue bars) (upper panel) and obese eWAT of anti-CSF1R antibody-injected mice (green bars) mice and isotype control-injected WT controls (white bars) (lower panel). Mice were under DT or anti-CSF1R antibody treatment for 12 days. (n = 5 pooled mice per group, mean ± SD). Statistical significance was determined using an unpaired Student's t-test. *P < 0.05, **P < 0.01, ***P < 0.001, ns: no significant difference.",
    "ncbi_link": "Abca1: 11303
Cd36: 12491
Dgat1: 13350
Fabp4: 11770
DTR: 15200
Lpl: 16956
Pparγ: 19016
CD169: 20612"
  },
  {
    "caption": "Violin plots depicting the expression of representative marker genes for each CD45- cell cluster: ASC1 (Gsn, Pdgfrb, Eln) (red), ASC2 (Pi16, Pdgfra, Cebpd) (yellow), stromal cells (Col1a1, Col1a2, Myl9) (green), VEC1/VEC2 (Pecam-1, Cldn5, Aqp1) (purple and blue), and mesothelial-like cells (MLCs) (Upk3b, Msln, Acta2) (orange).",
    "ncbi_link": "Acta2: 11475
Aqp1: 11826
Cebpd: 12609
Cldn5: 12741
Col1a1: 12842
Col1a2: 12843
Eln: 13717
Gsn: 227753
Msln: 56047
Myl9: 98932
Pdgfra: 18595
Pdgfrb: 18596
Pecam-1: 18613
Pi16: 74116
Upk3b: 100647"
  },
  {
    "caption": "Two representative images of eWAT dissected from Evans blue-injected obese (HFD 16 weeks) WT and CD169-DTR mice treated for 7 days with DT. Evans blue dye was extracted from eWAT using formamide and the absorption of the extract was measured at 620 nm (the absorption values were normalized to the tissue weight in grams). A chart showing the normalized mean optical density ± SD (n = 5-7 mice per group). Statistical significance was determined using an unpaired Student's t-test. ***P < 0.001.",
    "ncbi_link": "DTR: 15200
CD169: 20612"
  },
  {
    "caption": "Mmp12 (H) and Vegfα (F) are highly expressed in MHCIIhi and CD11c+ ATMs purified from obese (HFD 16 weeks) eWAT. qPCR analysis showed the relative expression in all three ATM subsets (n=3), data was expressed as mean ± SD . Statistical significance between the three ATM subpopulations was determined using one-way ANOVA test. *P < 0.05, **P < 0.01. qPCR analysis showing the relative expression of Vegfα in obese (HFD 16 weeks) eWAT of WT (n=3) or CD169-DTR mice (n=5) treated for 7 days with DT, data was expressed as mean ± SD. Statistical significance was determined using an unpaired Student's t-test. ****P < 0.0001.",
    "ncbi_link": "DTR: 15200
CD11c: 16411
Mmp12: 17381
CD169: 20612
Vegfα: 22339"
  },
  {
    "caption": "Elastin staining showing more pronounced ECM accumulation in eWAT of CD169-DTR (HFD 16 weeks) when compared with ECM accumulation in the WT obese (HFD 16 weeks) control (DAPI, blue; elastin, red; CD31, green). The fourth image in each row shows the three channels merged. Scale bar: 50 μm. Picrosirius red-staining depicts excessive collagen deposits in obese (HFD 16 weeks) eWAT of CD169-DTR mice when compared with collagen deposits in WT controls. Scale bar: 250 μm. Upper panels: brightfield microscopy; lower panels: fluorescence microscopy.",
    "ncbi_link": "DTR: 15200
CD169: 20612"
  },
  {
    "caption": "Violin plots showing the pro-inflammatory cytokine profile (Il-6, Tnf-α, and Il-1β) of all 23 cell clusters obtained from obese (HFD 16 weeks) WT and CD169-DTR eWAT. Cluster 0: ASC1; Cluster 1: Stromal cells; Cluster 2: VEC1; Cluster 3: VEC2; Cluster 4: NK1; Cluster 5: MAC/Mono1; Cluster 6: ASC2; Cluster 7: B; Cluster 8: cDC1; Cluster 9: mono-derived cDC; Cluster 10: Th2/ILC2/Treg; Cluster 11: MAC/Mono3; Cluster 12: Th17; Cluster 13: VEC2; Cluster 14: CD8; Cluster 15: MLCs; Cluster 16: CD11b+ DC; Cluster 17: Neutrophils; Cluster 18: cDC2; Cluster 19: cDC; Cluster 20: NKT; Cluster 21: NK2; Cluster 22: Mast cells/Basophils. ASC: adipocyte stem cell; VEC: vascular endothelial cell; MLC: mesothelial-like cell; NK: natural killer; MAC: macrophage; Mono: monocyte; DC: dendritic cell; NKT: natural killer T cells.",
    "ncbi_link": "DTR: 15200
Il-1β: 16176
Il-6: 16193
CD169: 20612
Tnf-α: 21926"
  },
  {
    "caption": "(A) Consecutive in vivo imaging of the same apical dendrites from layer V pyramidal neurons in the somatosensory cortex over 7 weeks reveals formation and elimination of dendritic spines (white and empty arrowheads, respectively) in WT and APP-KO mice. All mice were housed in standard conditions. Scale bar - 10 μm. (B-E) Graphical representations of the relative spine density, spine turnover rate (TOR), elimination and formation over the imaging period. Non-linear regression (F test) has been used for fitting the data points and comparing the difference between groups. N=4 mice per group ** p<0.01.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Consecutive in vivo imaging of the same apical dendrites from layer V pyramidal neurons in the somatosensory cortex over 46 days reveals formation and elimination of dendritic spines (white and empty arrowheads, respectively) in WT and APP-KO mice. Prior to the exposure to environmental enrichment (EE), all mice were housed in standard conditions. Scale bar - 10 μm. (B-C) Graphical representations of the relative spine density and spine elimination over the period of the exposure of mice to EE. Non-linear regression (F test) has been used for fitting the data points. Repeated one-way ANOVA was performed followed by Dunnett test. WT n=5 mice and APP-KO n=6 mice; * p<0.05, ** p<0.01, NS - no significant difference.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Typical confocal images of apical dendrites with spines (z-projections) from layer V pyramidal neurons in the somatosensory cortex of WT and APP-KO mice (top and bottom) housed in standard and enriched environments (left and right). For classification of spine types, 3D reconstructions by Imaris have been applied. Thin, mushroom and stubby spines are encoded in blue, green and red, respectively. Scale bar represents 2 μm. (B-C) Summary plots of thin and mushroom spine fractions in WT and APP-KO mice exposed to standard (SE) and enriched environments (EE). . Two-tailed Student t-test was used and n=6 mice in all experimental groups; * p<0.05, ** p<0.01, NS - no significant difference.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(B, C) High performance liquid chromatography was performed to quantify total D-serine and L-serine contents in mouse brain of two genotypes. APP-KO mice were fed with D-serine over one month. One-way ANOVA was used for analysis followed by Bonferroni's multiple comparisons test and n>6 mice per group; * p<0.05, ** p<0.01 as compared to WT.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Consecutive in vivo imaging of the same apical dendrites from layer V pyramidal neurons in the somatosensory cortex of APP-KO mice housed under standard or enriched environment. Note that both groups of mice received D-serine after the second imaging time point (8 d); white and empty arrowheads point to newly formed and eliminated spines, respectively. Scale bar - 10 μm. (B) Spine TOR prior and during continuous D-serine treatment. (C, D) Summary plots of the fraction of spine elimination and formation in APP-KO mice before and after D-serine treatment (8 d and 46 d, respectively). (E) Relative spine densities in D-serine treated APP-KO mice housed under standard and enriched environments. (F, G) Summary plots of the fraction of thin and mushroom spines in control and D-serine treated APP-KO mice. For illustration purpose, the control data from Figure 2 B and C are presented also here. Non-linear regression (F test) has been used for fitting the data points. Two-tailed Student t-test was used in (C-D, F-G) and repeated one-way ANOVA was performed followed by Dunnett test in (B and E). N=5 mice in each group; * p<0.05, ** p<0.01, NS - no significant difference.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Volcano plot representation of PARL interaction partners. Mitochondria isolated from PARL-/- FITR293Tcells expressing PARL-FLAG were subjected to co-immunoprecipitation (IP). Co-purifying proteins were separated by SDS-PAGE and identified by quantitative MS (n=3)(Dataset EV1).",
    "ncbi_link": "PARL: 55486"
  },
  {
    "caption": "(B) Heat map of Log2 transformed LFQ intensities for three independent experiments. All significant (FDR < 0.05) proteins showing a positive ratio between PARLIP and control in (A) are shown. Grey color shows missing quantitative information. Clustering was performed using the complete method with Euclidean distance.",
    "ncbi_link": "PARL: 55486"
  },
  {
    "caption": "(D) BN-PAGE analysis of mitochondria lacking SLP2, YME1L or PARL. Mitochondria isolated from corresponding MEFs were solubilized using 1.5% (w/v) digitonin at a protein concentration of 2.5 mg/ml. Solubilized proteins were separated by a 3-13% blue native gradient gel and analyzed using SLP2-, YME1L- and PARL-specific antibodies.",
    "ncbi_link": "PARL: 381038
SLP2: 66592
YME1L: 27377"
  },
  {
    "caption": "(B, C) Co-immunoprecipitation of endogenous SLP2 and YME1L with PARL-specific antibodies in mitochondria isolated from wild type MEFs (WT) and MEFs lacking YME1L, SLP2 or PARL. In, input (10%).",
    "ncbi_link": "PARL: 381038
SLP2: 66592
YME1L: 27377"
  },
  {
    "caption": "(B, C) Co-immunoprecipitation of endogenous SLP2 and YME1L with PARL-specific antibodies in mitochondria isolated from wild type MEFs (WT) and MEFs lacking YME1L, SLP2 or PARL. In, input (10%).",
    "ncbi_link": "PARL: 381038
SLP2: 66592"
  },
  {
    "caption": "(D) Assembly of SLP2, PARL and YME1L into a high molecular weight complex. Mitochondria isolated from FITR293T cells (Con) and cells inducibly expressing SLP2-FLAG (FLAG) were solubilized in digitonin and subjected to immunoprecipitation using FLAG-specific antibodies. Native eluates of the precipitate were analyzed by BN-PAGE and immunoblotting using SLP2-, PARL-, YME1L- and PHB2-specific antibodies. In, input (8%); E, eluate (100%).",
    "ncbi_link": "SLP2: 66592"
  },
  {
    "caption": "(E) High resolution BN-PAGE analysis of mitochondria lacking PARL, YME1L or SLP2. Mitochondria isolated from corresponding MEFs were solubilized using 1.5% (w/v) digitonin at a protein concentration of 2.5 mg/ml. Solubilized proteins were separated by a 3-9% gradient gel containing 0-10% glycerol and analyzed using SLP2-specific antibodies.",
    "ncbi_link": "PARL: 381038
SLP2: 66592
YME1L: 27377"
  },
  {
    "caption": "(A) Steady state levels of proteolytic substrates of YME1L. Whole cell extracts of Yme1l-/-, Parl-/-, and Slp2-/- MEFs were analyzed by SDS-PAGE and immunoblotting using the indicated antibodies.",
    "ncbi_link": "Parl: 381038
Slp2: 66592
Yme1l: 27377
YME1L: 27377"
  },
  {
    "caption": "(B) PGAM5 processing depends on proteolytically active PARL. PARL and catalytic inactive PARLS277A harboring C-terminal FLAG-epitopes were expressed under the control of a tetracycline (tet)-inducible promoter in wild type (WT) and PARL-/- FITR293T cells as indicated. Processing of L-PGAM5 to S-PGAM5 was monitored by immunoblotting.",
    "ncbi_link": "PARL: 55486"
  },
  {
    "caption": "(C) Accelerated processing of L-PGAM5 in Slp2-/- cells. Processing of L-PGAM5 was analyzed by immunoblotting in wild type (WT), Yme1l-/-, Parl-/- and Slp2-/-MEFs after inhibition of cytosolic protein synthesis by cycloheximide (CHX). A quantification of L-PGAM5 levels at different time points is shown in the lower panel. Two-way ANOVA analysis (n=3; ****, p<0.0001).",
    "ncbi_link": "Parl: 381038
Slp2: 66592
Yme1l: 27377"
  },
  {
    "caption": "(D) The accelerated processing of L-PGAM5 in Slp2-/- cells is mediated by PARL. PARL was depleted from Slp2-/- cells by RNAi prior to CHX treatment. A quantification of L-PGAM5 levels at different time points is shown. Two-way ANOVA analysis (n=3; **, p<0.01. ****, p<0.0001).",
    "ncbi_link": "PARL: 381038
Slp2: 66592"
  },
  {
    "caption": "(E) PGAM5 associates with the SPY complex harboring proteolytically inactive PARL. Mitochondria isolated from FITR293T cells (WT) or PARL-/- FITR293T cells expressing PARL-FLAG (PARL-WT) or PARLS277A-FLAG (PARL-S277A) were solubilized in digitonin were analyzed by BN-PAGE and immunoblotting using FLAG- and PGAM5-specific antibodies.",
    "ncbi_link": "PARL: 55486"
  },
  {
    "caption": "(A) PARL dependent cleavage of PINK1-HA is reduced in Slp2-/- and Yme1l-/- MEFs. Whole cell extracts of Slp2-/-, Parl-/ -and Yme1l-/- MEFs expressing PINK1-HA were analysed by SDS-PAGE and immunoblotting using the indicated antibodies. Cells were treated with 20 µM MG132 or 20 µM CCCP for 4 h.(B) Quantification of the protein ratio (Log2) PINK1-HA 52 kDa/63 kDa (n=3; *, p<0.05; One-way ANOVA). n.s., not significant. Error bars indicate SEM.",
    "ncbi_link": "Parl: 381038
Slp2: 66592
Yme1l: 27377"
  },
  {
    "caption": "(C) PINK1-HA associates with the SPY complex harboring proteolytically inactive PARL. Mitochondria isolated from FITR293T cells (WT) or PARL-/- FITR293T cells expressing PARL-FLAG (PARL-WT) or PARLS277A-FLAG (PARL-S277A) were solubilized in digitonin and analysed by BN-PAGE and immunoblotting using FLAG-, HA- and SLP2-specific antibodies.",
    "ncbi_link": "PARL: 55486"
  },
  {
    "caption": "(D) PINK1 associates with SLP2. Mitochondria isolated from FITR293T cells (WT) or PARL-/- FITR293T cells, depleted of SLP2 by siRNA as indicated, were solubilized in digitonin and analysed by BN-PAGE and immunoblotting using SLP2- and PINK1-specific antibodies.",
    "ncbi_link": "PARL: 55486
SLP2: 30968"
  },
  {
    "caption": "(A) Processing of L-PGAM5 to S-PGAM5 in depolarized mitochondria of wild type (WT), Slp2-/-, Yme11-/-, and Parl-/- MEFs. PGAM5 processing was monitored by immunoblotting at the indicated time points after inhibition of cytosolic protein synthesis with cycloheximide (CHX). A quantification of L-PGAM5 levels at different time points is shown. L-PGAM5 levels at t=0 was set to 100%. Two-way ANOVA analysis (n=3; *, p<0.05, **, p<0.01. ****, p<0.0001). Arrowheads denote intermediate PGAM5 cleavage products.",
    "ncbi_link": "Parl: 381038
Slp2: 66592
Yme11: 27377"
  },
  {
    "caption": "(B) OMA1-mediated processing of PGAM5 in depolarized Parl-/-mitochondria. Processing of L-PGAM5 to S-PGAM5 in Parl-/ mitochondria was assessed as in (A) in the presence or absence of CCCP (20 µM), which were depleted of OMA1 by siRNA as indicated. The arrowhead denotes an intermediate PGAM5 cleavage product. SCR, scrambled.",
    "ncbi_link": "OMA1: 67013
Parl: 381038"
  },
  {
    "caption": "(C) Impaired PGAM5 processing in depolarized Oma1-/- mitochondria lacking PARL. Processing of L-PGAM5 to S-PGAM5 was examined as in (A) after 2 h in wild type (WT) and Oma1-/- mitochondria in the presence or absence of CCCP (20 µM, 2 h), which were depleted of PARL by siRNA as indicated. * unspecific cross-reaction.",
    "ncbi_link": "Oma1: 67013
PARL: 381038"
  },
  {
    "caption": "(D) OMA1 mediates accelerated processing of L-OPA1 in Slp2-/- MEFs. Processing of OPA1 and PGAM5 was monitored in Slp2-/-, Oma1-/-, and Slp2-/-Oma1-/- cells by immunoblotting after inhibition of cytosolic protein synthesis with cycloheximide (CHX).",
    "ncbi_link": "Oma1: 67013
OMA1: 67013
Slp2: 66592"
  },
  {
    "caption": "(E) OMA1 interacts with SLP2. OMA1-/-FITR293T cells ectopically expressing OMA1-myc were transfected with pcDNA5 (Control) or pcDNA5-SLP2-FLAG (FLAG). Isolated mitochondria were solubilized in digitonin and subjected to immunoprecipitation using FLAG-specific antibodies. Native eluates of the precipitate were analyzed by BN-PAGE and immunoblotting using SLP2-, YME1L-, PARL-, and myc-specific antibodies. In, input (8%); E, eluate (100%). Samples were analyzed by SDS-PAGE in parallel (lower panel).(F) Quantification of immunoprecipitation efficiencies in (E).",
    "ncbi_link": "OMA1: 115209
SLP2: 30968"
  },
  {
    "caption": "A Spleen weights  of RUNX1-RUNX1T1  or I1DN tumor bearing mice  treated with AG636  or vehicle for 4 days. Data information: n = 5-6 mice/group for RUNX1-RUNX1T1  model, n = 4 mice/group for I1DN model; data are presented as mean ± s.d.; P values were calculated using a one-tailed Student's unpaired t-test. *P < 0.05, **P < 0.01.",
    "ncbi_link": "RUNX1: 12394
RUNX1T1: 12395"
  },
  {
    "caption": "B-C Absolute number of  leukemic cells  in the  bone marrow  (B) and spleens (C) of RUNX1-RUNX1T1  or I1DN tumor bearing mice  treated with AG636 or vehicle for 4 days. Data information: n = 5-6 mice/group for RUNX1-RUNX1T1  model, n = 4 mice/group for I1DN model; data are presented as mean ± s.d.; P values were calculated using a one-tailed Student's unpaired t-test. *P < 0.05, **P < 0.01.",
    "ncbi_link": "RUNX1: 12394
RUNX1T1: 12395"
  },
  {
    "caption": "D-E Frequency of  leukemic cells expressing  the immature marker cKit  and mature myeloid  marker CD11b  in the bone marrow and spleens  of RUNX1-RUNX1T1  (D) or I1DN (E) tumor bearing mice  treated with AG636  or vehicle for 4 days (n = 6 mice/group). Data information: n = 5-6 mice/group for RUNX1-RUNX1T1  model, n = 4 mice/group for I1DN model; data are presented as mean ± s.d.; P values were calculated using a one-tailed Student's unpaired t-test. *P < 0.05, **P < 0.01.",
    "ncbi_link": "RUNX1: 12394
RUNX1T1: 12395"
  },
  {
    "caption": "C  RNA sequencing performed on  cKit+CD11b- RUNX1-RUNX1T1  or I1DN cells sorted from mice  treated with AG636  or vehicle for 1 day (n = 3 mice/group). Bar code plots showing enrichment of selected pathways.",
    "ncbi_link": "RUNX1: 12394
RUNX1T1: 12395"
  },
  {
    "caption": "G qPCR showing down-regulation of genes encoding ribosomal  proteins that are putative YY1  targets in Cas9  expressing MN  cells treated with AG636  or DMSO  (left); or transduced with sgRNAs targeting YY1  or control sgRNAs (right) (n = 2 biological replicates). Data information: data in G are presented as mean ± s.e.m.; P values were calculated using a one-tailed Student's unpaired t-test in G; *P < 0.05, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "Cas9: 69900935
YY1: 22632"
  },
  {
    "caption": "H Barcode plots showing downregulation of the Reactome Translation gene set in YY1  knockout pro B cells and human melanoma  cells upon YY1  knockdown",
    "ncbi_link": "YY1: 22632
YY1: 7528"
  },
  {
    "caption": "a, Ultrasonic vocalizations (USV) in isolated miR379-410 ko mouse pups emitted on postnatal day P3, P6, P9 and P12. Left panel: total number of ultrasonic vocalizations (USV) in isolated miR379-410 wt and ko mouse pups emitted on average (P 3, 6, 9 and 12) when isolated from the mother, wt n=13 (male n=9, female n=4), ko n=20 (male n=11, female n=9), t31=2.274, *p=0.0301, unpaired Student's t-test. Right panel: developmental course for total number of USV, wt n=13 (male n=9, female n=4), ko n=20 (male n=11, female n=9), (development: F3,87=25.463, p<0.001; genotype: F1,29=4.979, p=0.03; development x genotype: F3,87=1.403, p= 0.22, rm-ANOVA); P 9: t31=2.096, *p=0.044; unpaired Student`s t-test.",
    "ncbi_link": "miR379-410: 100124453///100124450///723881///723941///102465218///751524///723940///723862///723912///723935///723859///723857///723855///723933///723839///723833///387172///387152///723842///751522///723875///723863///723858"
  },
  {
    "caption": "b, Reciprocal social interaction in juvenile miR379-410 wt- and ko mice pairs (P23). Aberrant time spending in social interaction activity in miR379-410 ko-pairs compared to their control wt littermate pairs. Left panel: wt-pairs male n=13, ko-pairs male n=10, t21=2.433, *p=0.0240, unpaired Student's t-test. Middle panel: wt-pairs female n=15, ko-pairs female n=13, t26=1.873, ns p=0.0723, unpaired Student's t-test. Right panel: pooled data of wt-pairs n=28 (male n=13, female n=15), ko-pairs n=23 (male n=10, female n=13), t49=2.969, **p=0.005; unpaired Student`s t-test.",
    "ncbi_link": "miR379-410: 100124453///100124450///723881///723941///102465218///751524///723940///723862///723912///723935///723859///723857///723855///723933///723839///723833///387172///387152///723842///751522///723875///723863///723858"
  },
  {
    "caption": "A, B Single-molecule FISH (smFISH) on mouse hippocampal neurons. (A) Representative pictures of smFISH on BDNF-treated WT (top) and KO (bottom) mouse hippocampal neurons (DIV6) using a probe directed against the Mirg transcript (green). (Middle) Hoechst (blue). (Right) MAP2 immunostaining (red). Pictures show a zoom-in on the cell body, since the signal detected in WT neurons was restricted to the nuclei (scale bar: 5μm). (B) Representative pictures of smFISH on mouse wild type hippocampal neuron cultures (DIV6; basal) using a probe specific for the Mirg transcript (green). (Middle) Hoechst (blue). (Right) MAP2 immunostaining (red). Top: overview, scale bar: 10μm; bottom: zoom-in, scale bar: 5μm.",
    "ncbi_link": "Mirg: 100040724"
  },
  {
    "caption": "C, D, Patch-clamp electrophysiological recordings in cultured mouse hippocampal neurons (DIV 8-10) isolated from wt or miR379-410 ko animals (n=3 per group). (C) Cumulative distribution (left panel, D=0.25, p<0.0001, KS-test) and mean (right panel, t16=2.736, *p=0.0146, unpaired Student`s t-test) of mEPSC inter-event intervals; wt n=9, ko n=9 cells analyzed. (D) Cumulative distribution (left panel, D=0.34741, p<0.0001, KS-test) and mean (right panel, t18=2.357, *p=0.0299, unpaired Student`s t-test) of mEPSC amplitudes; wt n=10, ko n=10 cells analyzed.",
    "ncbi_link": "miR379-410: 100124453///100124450///723881///723941///102465218///751524///723940///723862///723912///723935///723859///723857///723855///723933///723839///723833///387172///387152///723842///751522///723875///723863///723858"
  },
  {
    "caption": "e, Representative confocal images of CA1 pyramidal neuron apical dendrites from adult Thy1-GFP/miR379-410 wt and Thy1-GFP/miR379-410 ko mouse tissue. Scale bar: 10 µm. f, Spine density in CA1 pyramidal neurons of adult male Thy1-GFP/miR379-410 wt and ko mice; wt n=5, ko n=6 animals. Mean of basal and apical neurons per mouse are shown, t9=3.662, **p=0.0052, unpaired Student`s t-test. g, Spine volume in CA1 pyramidal neurons of adult Thy1-GFP/miR379-410 wt and ko mice; wt n=5, ko n=6 animals. Mean of basal and apical neurons per mouse are shown, t9=2.265, *p=0.0497, unpaired Student`s t-test. ",
    "ncbi_link": "miR379-410: 100124453///100124450///723881///723941///102465218///751524///723940///723862///723912///723935///723859///723857///723855///723933///723839///723833///387172///387152///723842///751522///723875///723863///723858"
  },
  {
    "caption": "b, qPCR validation of predicted direct miR379-410 targets using RNA from hippocampi of juvenile (P 22-24) mice, except of Shank 3 where adult miR-379-410 wt and ko animals were measured. If not indicated, both, male and female samples were used. Cnih2 (wt n=12, ko n=9, t19=2.344, *p=0.0301), Dlgap3 (wt n=12, ko n=9, t19=2.128, *p=0.0467), Prr7 (male wt n=7, ko n=4, t9=2.719, *p=0.0236), Src (wt n=12, ko n=9, t19=2.410, *p=0.0263), Lzts2 (male wt n=7, ko n=4, t9=2.554, *p=0.0310), Mpp2 (male wt n=7, ko n=4, t9=2.369, *p=0.0420), Prr12 (wt n=6, ko n=4, t8=2.375, *p=0.0449), Shank1 (wt n=11, ko n=9, t18=2.310, *p=0.0329), Shb (male wt n=6, ko n=4, t8=3.451, **p=0.0087) and Shank3 (adult male wt n=3, ko n=5, t6=2.538, *p=0.0442); unpaired Student`s t-test. Data are presented as mean ± s.e.m.",
    "ncbi_link": "Cnih2: 12794
Dlgap3: 242667
Lzts2: 226154
miR-379-410: 723858///723842///723863///723875///751522
miR379-410: 100124453///100124450///723881///723941///102465218///751524///723940///723862///723912///723935///723859///723857///723855///723933///723839///723833///387172///387152///723842///723858///723863///723875///751522
Mpp2: 50997
Prr12: 233210
Prr7: 432763
Shank1: 243961
Shank 3: 58234
Shank3: 58234
Shb: 230126
Src: 20779"
  },
  {
    "caption": "c, d, Cnih2, Prr7 and Src are direct miR-379-410 target mRNAs. (C) 3'-UTR luciferase reporter gene assays in cultured rat cortical neurons using the indicated 3'UTR reporter genes (wt or seed mutant) together with miRNA mimics. Cnih2 (n=3 per group; wt: **p=0.0020, mut: p=0.9267; mimic: F1,8=19.92, p=0.0021; utr-construct: F1,8=4.760, p=0.0607; mimic x utr-construct: F1,8=12.99, p=0.0069), Prr7 (n=3 per group; wt: ****p<0.0001, mut: *p=0.0103; wt vs. mut mimic miR329: **p=0.0014; mimic: F1,8=153.1, p<0.0001; utr-construct: F1,8=5.631, p=0.0450; mimic x utr-construct: F1,8=38.54, p=0.0003); Src (n=3 per group; wt: *p=0.0110, mut: p=0.4724; mimic: F1,8=16.99, p=0.0033; utr-construct: F1,8=0.6809, p=0.4332; mimic vs. utr-construct: F1,8=3.920, p=0.0831); two-way ANOVA. (D) Same as in (C), but in the presence of antimiRs (pLNAs) in hippocampal neurons after 48h of PTX stimulation. Cnih2 (n=4 per group; wt: p=0.2688; mut: p=0.8668; wt ctr vs. mut ctr: p=0.6463; anti-miRNA: F1,12=3.629, p=0.0810; utr-construct: F1,12=0.7407, p=0.4063; anti-miRNA x utr-construct: F1,12=0.6679, p=0.4297), Prr7 (n=4 per group; wt: *p=0.0123; mut: p=0.9917; wt ctr vs. mut ctr: *p=0.0152; anti-miRNA: F1,12=6.082, p=0.0297; utr-construct: F1,12=5.271; p=0.0405; anti-miRNA x utr-construct: F1,12=8.212, p=0.0142); Src (n=3 per group; wt: *p=0.0370; mut: p=0.3540; wt ctr vs. mut ctr: p=0.9906; anti-miRNA: F1,12=13.43, p=0.0064; utr-construct: F1,12=0.5672, p=0.4730; anti-miRNA x utr-construct: F1,12=1.362, p=0.2768); two-way ANOVA. Data are presented as mean ± s.d.",
    "ncbi_link": "Cnih2: 12794
miR329: 723842
miR-379-410: 751522///723875///723863///723842///723858
Prr7: 432763
Src: 20779"
  },
  {
    "caption": "C-D Bar charts with individual points showing the mRNA expression levels of CB1 and CB2 measured in the gastrocnemius of the indicated groups of mice.",
    "ncbi_link": "CB1: 12801
CB2: 12802"
  },
  {
    "caption": "A-C Bar charts with individual points showing the mRNA expression levels of Ulk, Pink and Becn1 measured in control and mdx mice treated with rimonabant (0.5 mg kg-1).",
    "ncbi_link": "Becn1: 56208
Pink: 18431
Ulk: 22241"
  },
  {
    "caption": "A-B Bar chart with individual points showing the mRNA expression levels of Il6 and Cox2 in control (vehicle, DMSO) and/or GPR109A-silenced C2C12 myoblasts exposed to LPS (1 μg/ml) in the presence or absence of either MK1903 (1 μM), rosiglitazone (1 μM) or T007 (1 μM).",
    "ncbi_link": "Cox2: 17709
GPR109A: 80885
Il6: 16193"
  },
  {
    "caption": "A-F Bar chart with individual points showing the mRNA expression levels of Cb1, Daglα, Daglβ, Magl, Napepld, and Faah in control (vehicle, DMSO) and/or GPR109A-silenced C2C12 myoblasts exposed to LPS (1 μg/ml) in the presence or absence of either MK1903 (1 μM), rosiglitazone (1 μM) or T007 (1 μM).",
    "ncbi_link": "Cb1: 12801
Daglα: 269060
Daglβ: 231871
Faah: 14073
GPR109A: 80885
Magl: 23945
Napepld: 242864"
  },
  {
    "caption": "C-J Bar chart with individual points showing the expression of selected miRNAs in control and Gpr109A-silenced C2C12 myoblasts exposed to LPS (1 μg/ml) in the presence or absence of either NaB (3 mM), MK1903 (1 μM), rosiglitazone (1 μM). NaB was also tested in the presence or absence of either rosiglitazone (1 μM) or T007 (1 μM).",
    "ncbi_link": "Gpr109A: 80885"
  },
  {
    "caption": "A-E Bar chart showing the mRNA expression levels of IL6, COX2, ULK 1, ATG13 and ATG4 mRNA in primary human myoblasts isolated from one healthy donor (HD) and five DMD donors (D1- D5).",
    "ncbi_link": "ATG13: 9776
ATG4: 23192
COX2: 4513
IL6: 3569
ULK 1: 8408"
  },
  {
    "caption": "(A) Representative micro-CT images and H&E staining of trabecular bone from the femoral metaphysis of 6-week-old male Sp7-Cre;Cdc20f/f and littermate control mice. Scale bar, 500 μm. (B) Histomorphometric analyses of 6-week-old male femurs. (n=6)",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
Sp7: 170574"
  },
  {
    "caption": "(C) Representative micro-CT images and H&E staining of trabecular bone from the femoral metaphysis of 6-week-old female Sp7-Cre;Cdc20f/f and littermate control mice. Scale bar, 500 μm. (D) Histomorphometric analyses of 6-week-old female femurs. (n=6) ",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
Sp7: 170574"
  },
  {
    "caption": "(E) Representative micro-CT images of tibial cortical bone defects in Sp7-Cre;Cdc20f/f and littermate control mice. The green lines show the position of the original defect position. The green circle represents the regenerated bone. Scale bar, 500 μm. (F) Histomorphometric analysis of the regenerated bone in tibial cortical gaps. (n=5) ",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
Sp7: 170574"
  },
  {
    "caption": "(B, C) The ALP staining (B) and ALP quantification (C) of Cdc20f/f and Sp7-Cre;Cdc20f/f BMSCs after 7 days osteogenic differentiation. (n=6)",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
Sp7: 170574"
  },
  {
    "caption": "(E, F) The ALP staining (E) and ALP quantification (F) of NC and CDC20sh hBMSCs after 7 days osteogenic differentiation. (n=5)",
    "ncbi_link": "CDC20: 991"
  },
  {
    "caption": "(H, I) The ALP staining (H) and ALP quantification (I) of Vector and truncated fragments overexpression of CDC20 in CDC20sh hBMSCs after 7 days osteogenic differentiation. (n=5)",
    "ncbi_link": "CDC20: 991"
  },
  {
    "caption": "(E) Western blot analyses of the degradation of nuclear p65 protein after the overexpression of CDC20. The cytoplasmic and nuclear protein of overexpressed Myc-CDC20 and Vector HEK293T cells were extracted after TNF-α treatment for 30 minutes.",
    "ncbi_link": "CDC20: 991"
  },
  {
    "caption": "(G) Western blot analyses of the degradation of p65 protein after the overexpression of Myc-CDC20. hBMSCs were transfected with Vector and Myc-CDC20 plasmids for 36 h, cells were treated with or without 10 μM MG132 for 6 h before collected.",
    "ncbi_link": "Myc: 
CDC20: 991"
  },
  {
    "caption": "(G) Co-immunoprecipitation of purified GST-CDC20 protein with endogenous p65 in HEK293T cells and the construct of GST-CDC20. Whole cell lysates (WCL) were subjected to perform GST pull-down analyses with purified GST-CDC20 and GST as a negative control.",
    "ncbi_link": "GST: 
CDC20: 991"
  },
  {
    "caption": "(C) Western blot analyses of the degradation of p65 protein in NC and APC11si HEK293T cells.",
    "ncbi_link": "APC11: 51529"
  },
  {
    "caption": "(F) Western blot analyses of p65 expression in NC or CDC20sh HEK293T cells after the overexpression of Vector or HA-APC11 plasmids.",
    "ncbi_link": "HA: 
APC11: 51529
CDC20: 991"
  },
  {
    "caption": "(H, I) The ALP staining (H) and ALP quantification (I) of NC and APC11si hBMSCs after 7 days osteogenic differentiation. (n=6)",
    "ncbi_link": "APC11: 51529"
  },
  {
    "caption": "(A) Immunoblot of Flag-p65-linked ubiquitination promoted by Myc-CDC20. HEK293T cells were co-transfected with Flag-p65, HA-Ubiquitin, with or without Myc-CDC20 or Vector plasmids for 36 h. Transfected cells were then treated with 10 μM MG132 for 6 h before collection. (B) Immunoblot of Flag-p65-linked ubiquitination promoted by HA-APC11. HEK293T cells were transfected with Flag-p65, His-Ubiquitin, with or without HA-APC11 or Vector plasmids for 36 h. Transfected cells were then treated with 10 μM MG132 for 6 h before collection. ",
    "ncbi_link": "HA: 
Myc: 
APC11: 51529
CDC20: 991"
  },
  {
    "caption": "(F) Immunoblot of Flag-p65-linked ubiquitination promoted by HA-APC11 in NC and CDC20sh cells. NC or CDC20sh HEK293T cells were co-transfected with Flag-p65, His-Ubiquitin, with or without HA-APC11 and Vector plasmids. Transfected cells were treated with 10 μM MG132 for 6 h before collection.",
    "ncbi_link": "HA: 
APC11: 51529
CDC20: 991"
  },
  {
    "caption": "(A) Representative micro-CT images of trabecular bone from the femoral metaphysis of Cdc20f/f with negative control lentivirus, Sp7-Cre;Cdc20f/f with negative control lentivirus, and Sp7-Cre;Cdc20f/f with p65sh lentivirus. Scale bar, 500 μm. (B) Histomorphometric analyses of Cdc20f/f with negative control lentivirus, Sp7-Cre;Cdc20f/f with negative control lentivirus, and Sp7-Cre;Cdc20f/f with p65sh lentivirus. (n=6) ",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
p65: 19697
Sp7: 170574"
  },
  {
    "caption": "(C, D) The ALP staining (C) and ALP quantification (D) of BMSCs from Cdc20f/f mice and Sp7-Cre;Cdc20f/f mice after 7 days osteogenic differentiation treated with negative control or p65si. (n=5)",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
p65: 19697
Sp7: 170574"
  },
  {
    "caption": "(G) The expression of RUNX2 in BMSCs from Cdc20f/f mice and Sp7-Cre;Cdc20f/f mice after 7 days osteogenic differentiation treated with negative control or p65si by western blot analyses.",
    "ncbi_link": "Cdc20: 107995
Cre: 2777477
p65: 19697
Sp7: 170574"
  },
  {
    "caption": "C Representative immunofluorescence microscopy staining of Msi1 of small intestinal tissue of young mTerc+/+mice. Dashed line outlines a crypt. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm.D Quantification of Msi1 staining intensity of ISPCs at indicated positions in basal crypts of young mTerc+/+mice (n = 150 crypts from three mice). Each dot presents one cell. Red lines: mean values ± SEM. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "G-I mRNA expression of indicated genes relative to GAPDH in LGR5hi‐high, LGR5hi‐low, LGR5lo‐high, and LGR5lo‐low populations (n = 3 mice). Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "A mRNA expression of indicated components of the canonical Wnt/β‐catenin pathway in freshly isolated small intestinal crypts of 12‐ to 16‐month‐old G3 mTerc−/−mice and age‐matched mTerc+/+mice (n = 5 mice per group).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "B Axin2 mRNA expression in LGR5+ cells of 12‐ to 16‐month‐old G3 mTerc−/−mice and mTerc+/+mice (n = 3 mice per group).",
    "ncbi_link": "Axin2: 12006
Terc: 21748"
  },
  {
    "caption": "C mRNA expression of indicated components of the canonical Wnt/β‐catenin pathway and of the p53 target gene p21 in cultured crypts of 2‐month‐old G3 mTerc−/−mice and mTerc+/+mice (n = 3 mice per group).",
    "ncbi_link": "p21: 12575
Terc: 21748
p53: 22059"
  },
  {
    "caption": "A-J Flow cytometry analysis of freshly isolated crypt cells from the small intestine of young (2-3 month) and old (12-16 month) LGR5‐GFPki, mTerc+/+mice and LGR5‐GFPki, G3 mTerc−/−mice (n = 4 mice per group). (A, B, D, E, H, I) Representative FACS plots depicting the analysis of LGR5+ cells. Note the reduction in LGR5+ cells in G3 mTerc−/−mice with the remaining cells showing almost exclusively weak expression of GFP (LGR5lo) and that within the fraction of LGR5hi cells, the cells with high LGR5‐reporter activity (LGR5hi‐high) are preferentially depleted in response to IR. (C, F) Quantification of (C) the number of LGR5+ cells and (F) the number of LGR5hi and LGR5lo cells. (G) Quantification of the percentage of LGR5hi cells and LGR5lo cells within the fraction of LGR5+ cells. (J) Quantification of the survival rate of LGR5hi‐high cells and LGR5hi‐low cells within the fraction of LGR5hi cells comparing old G3 mTerc−/−mice to mTerc+/+mice.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "K-O Immunofluorescence microscopy staining of GFP in basal crypts of 9‐month‐old LGR5‐GFPki, G3 mTerc−/−mice and age‐matched LGR5‐GFPki, mTerc+/+mice (n = 2 mice per group). (K, L) Representative pictures are given. Dashed lines outline the crypts. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm. (M) Quantification of absolute number of GFP+ISPCs at indicated positions at the crypt base per 50 crypts. (N) The histogram depicts the depletion rate (%) of LGR5+ cells in LGR5‐GFPki, G3 mTerc−/−mice compared to age‐matched LGR5‐GFPki, mTerc+/+mice at indicated positions in the basal crypts. (O) Quantification of GFP staining intensity of ISPCs at indicated positions in positively stained basal crypts. Note that the staining intensity of position 4 cells is equal in mTerc+/+mice and G3 mTerc−/−mice and is significantly lower than position 1 and 2 cells of mTerc+/+mice.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A-I Staining of small intestinal tissue sections of 12‐ to 16‐month‐old G3 mTerc−/− mice and age‐matched mTerc+/+ mice (n = 4-5 mice per group). Representative pictures of (A, B) H&E staining, (C, F, I) Quantification of the absolute numbers of ISPCs at the indicated positions in the crypt base per 50 crypts as determined by counting of (C) spindle‐shaped cells in between and adjacent to the Paneth cells. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A-I Staining of small intestinal tissue sections of 12‐ to 16‐month‐old G3 mTerc−/−mice and age‐matched mTerc+/+mice (n = 4-5 mice per group). Representative pictures of (D, E) PCNA staining. Arrowheads and numbers indicate the position of ISPCs in the basal crypts. Scale bars: 20 μm. (C, F, I) Quantification of the absolute numbers of ISPCs at the indicated positions in the crypt base per 50 crypts as determined by counting of cells staining positive for (F) PCNA . Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A-I Staining of small intestinal tissue sections of 12‐ to 16‐month‐old G3 mTerc−/− mice and age‐matched mTerc+/+ mice (n = 4-5 mice per group). Representative pictures of ((G, H) Msi1 staining are given. Arrowheads and numbers indicate the position of ISPCs in the basal crypts. Scale bars: 20 μm. (C, F, I) Quantification of the absolute numbers of ISPCs at the indicated positions in the crypt base per 50 crypts as determined by counting of (I) Msi1. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "J, K Representative pictures of Olfm4 in situ hybridization on small intestinal sections of 9‐month‐old G3 mTerc−/− mice (K) and age‐matched mTerc+/+ (J) mice. Arrowheads point to positive cells. Dashed lines outline the crypts. Note that the remaining ISPCs in G3 mTerc−/− mice were mostly located in position 4 above the Paneth cells. Scale bar: 20 μm.",
    "ncbi_link": "Olfm4: 380924
Terc: 21748"
  },
  {
    "caption": "A-I Three‐month‐old mTerc+/+ mice were exposed to 12 Gy γ‐irradiation. Small intestinal tissue was collected at indicated time points after IR (n = 5 mice per group). (A-F) Representative pictures of PCNA staining. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm. Note the depletion of PCNA+ CBC cells in position 1 and 2 in between the Paneth cells at 3-48 h after IR and the regeneration of these cells at 4-6 days after IR. (G) Quantification of PCNA+ ISPCs at the indicated positions in basal crypts at the indicated time points after IR. Mean values ± SEM are given.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A-I Three‐month‐old mTerc+/+ mice were exposed to 12 Gy γ‐irradiation. Small intestinal tissue was collected at indicated time points after IR (n = 5 mice per group). (H, I) Representative pictures of Olfm4 in situ hybridization. Arrowheads point to positive cells. Dashed lines outline the crypts in irradiated samples. Scale bar: 20 μm. Note the selective survival of ISPCs above the Paneth cells at 24 h after IR.",
    "ncbi_link": "Olfm4: 380924
Terc: 21748"
  },
  {
    "caption": "J-X Three‐month‐old LGR5‐GFPki, mTerc+/+ mice were exposed to 12 Gy γ‐irradiation. Small intestinal tissue was collected at indicated time points after IR. (J-N) Representative pictures of GFP staining at indicated time points after irradiation. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "J-X Three‐month‐old LGR5‐GFPki, mTerc+/+mice were exposed to 12 Gy γ‐irradiation. Small intestinal tissue was collected at indicated time points after IR. (O-X) Flow cytometry analysis of freshly isolated basal crypt cells at the indicated time points after IR (n = 4-10 mice per group). (O) The histogram depicts the number of LGR5+ cells in freshly isolated basal crypts at the indicated time point after IR. (P, Q) Flow cytometry analysis was used to determine the percentage of (P) LGR5hi cells and (Q) LGR5lo cells within the fraction of LGR5+ cells. (R‐W) Representative FACS plots of small intestinal crypt cells of non‐irradiated mice, 24 h after irradiation. Note the reduction in LGR5+ cells in irradiated mice with the remaining cells showing almost exclusively weak expression of GFP (LGR5lo). (X) Quantification of the survival rate of LGR5hi‐high cells and LGR5hi‐low cells within the fraction of LGR5hi cells comparing irradiated mice to non‐irradiated mice. Note the preferential depletion of LGR5hi‐high cells within LGR5hi cell population upon IR. Mean values ± SEM are given. NIR, non‐irradiated; IR, irradiated.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "B, C LGR5hi and LGR5lo cells were freshly isolated from 3‐month‐old LGR5‐GFPki mice 6 h after 12 Gy γ‐irradiation (IR) or from non‐irradiated (NIR) mice (n = 3 mice per group). (B) qPCR analysis of relative mRNA expression of apoptosis‐related genes compared to GAPDH. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "D, E Three‐month‐old mTerc+/+ mice were γ‐irradiated with 12 Gy. Small intestinal tissue was collected at 3 h after IR (n = 3 mice per group). (D) Representative picture of TUNEL staining. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm. (E) Percentage of TUNEL‐positive ISPCs at indicated positions in basal crypts. Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "F-P Two‐month‐old LGR5‐GFPki, p53+/+ mice and LGR5‐GFPki, p53−/− mice were exposed to 12 Gy γ‐irradiation (n = 4 mice per group). Basal crypts were isolated at 24 h after IR. (F-H) Flow cytometry analysis of the survival rate of LGR5+ cells (F), LGR5hi and LGR5lo cells (G), and LGR5hi‐high and LGR5hi‐low cells (H) of irradiated mice (24 h after IR) compared to non‐irradiated mice (NIR). Mean values ± SEM are given. Unpaired two‐tailed Student's t‐test. (I-P) Representative FACS plots of LGR5+ cells in freshly isolated basal crypts from irradiated and non‐irradiated mice of indicated genotypes. Note the stronger rescue of survival rate of LGR5hi‐high than the LGR5hi‐low cells upon p53 deletion. NIR, non‐irradiated; IR, irradiated.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "A-G Two‐month‐old LGR5‐GFPki, mTerc+/+mice were i.v. injected with LRP6 neutralization antibody, and IgG serves as a negative control. Thirty‐six hours after injection, small intestinal tissue was collected for GFPimmunofluorescence microscopy staining. (A-F) Representative pictures are given. Dashed lines outline the crypts. Arrowheads and numbers indicate cell positions in the crypts. Scale bar: 20 μm. (G) Quantification of GFP staining intensity of cells at indicated positions in basal crypts (n = 3 mice per group, fifty positively stained cells were measured per mouse). Note the GFP staining intensity was substantially reduced in anti‐LRP6 antibody‐injected group with intact maintenance of ISPCs at the crypt bottom as shown by DAPI staining.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "H-L Two‐month‐old mTerc+/+ mice were i.v. injected with anti‐LRP6 antibody 12 h before γ‐irradiation. Small intestinal tissue was collected at 24 h after IR (n = 3-4 mice per group). IgG serves as a negative control. (H-K) Representative pictures of PCNA staining of small intestine of non‐irradiated mice (H, I) or 6 Gy‐irradiated mice (J, K). Note the anti‐LRP6 antibody injection did not induce loss of CBC cells at position 1 and 2 in non‐irradiated mice. Arrowheads and numbers indicate ISPC positions in the crypts. Scale bar: 20 μm. (L) Quantification of PCNA+ ISPCs at the indicated positions in basal crypts 24 h after IR with indicated doses or non‐irradiated mice.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "M-R Two‐month‐old LGR5‐GFPki, mTerc+/+ mice were i.v. injected with LRP6 neutralization antibody 12 h before 12 Gy γ‐irradiation. IgG serves as a negative control. Small intestinal tissue was collected at 24 h after IR (n = 4 mice per group). (M-P) Representative FACS plots of indicated treatments. (Q) Flow cytometry analysis of the number of LGR5+ ISPCs of irradiated mice compared to the number in non‐irradiated mice (NIR) set to 100%. (R) Quantification of the number of LGR5+, LGR5hi, and LGR5lo cells of mice with indicated treatment by flow cytometry. Note that the total LGR5+cell frequency was not significantly different between anti‐LRP6 antibody‐injected and control IgG‐injected mice, though the LGR5hi fraction was reduced in the LRP6 antibody‐injected group.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A-C GFPimmunofluorescence microscopy staining of small intestine from 2‐month‐old LGR5‐GFPki, APC+/+ mice and LGR5‐GFPki, APCmin/+mice. (A) Quantification of GFP staining intensity of cells at indicated positions in basal crypts (n = 3 mice per group, 50 positively stained cells were measured per mouse). Note the GFP staining intensity was increased in APCmin/+ mice, particularly in position 4 and 5 cells. (B, C) Representative pictures are given. Dashed lines outline the crypts. Arrowheads and numbers indicate cell positions in the crypts. Scale bar: 20 μm.",
    "ncbi_link": "APC: 11789"
  },
  {
    "caption": "D-F Two‐month‐old APC+/+ mice and APCmin/+ mice were exposed to 6 Gy γ‐irradiation. Small intestinal tissue was collected at 24 h after IR (n = 3 mice per group). (D) Quantification of PCNA+ ISPCs at the indicated positions in basal crypts 24 h after IR. IR, irradiated. (E, F) Representative pictures of PCNA staining are given. Arrowheads and numbers indicate cell positions in the crypts. Scale bar: 20 μm.",
    "ncbi_link": "APC: 11789"
  },
  {
    "caption": "G-K Two‐month‐old LGR5‐GFPki, APC+/+ mice and LGR5‐GFPki, APCmin/+ mice were exposed to 6 Gy γ‐irradiation. Small intestinal tissue was collected at 24 h after IR (n = 4 mice per group). (G) Flow cytometry analysis of the number of LGR5+ ISPCs of irradiated mice compared to the number in non‐irradiated mice (NIR) set to 100%. (H-K) Representative FACS plots of indicated groups are given.",
    "ncbi_link": "APC: 11789"
  },
  {
    "caption": "Representative Southern blots showing DSB repair products in WT, rad59∆, rad52-R70A and rad59∆ rad52-R70A cells. DNA was digested with Bsp1286I  and probed with a MAT-distal sequence (yellow box in panel B).",
    "ncbi_link": "rad52: 854976
rad59: 851500"
  },
  {
    "caption": "Representative Southern blots showing DSB repair products in WT, rad59∆, and rad52-R70A. DNA was digested with XhoI and EcoRI and probed with a Z sequence (yellow box).",
    "ncbi_link": "rad52: 854976
rad59: 851500"
  },
  {
    "caption": "Schematic of mutation analysis during allelic recombination (left). Mutation reporter cassette is inserted within the repair template 16 kb away from strand invasion site. Mutation rate (right) of WT, rad59∆, rad52-R70A was calculated as previously described (Saini et. al., 2013). Data information: χ  Mutation rates are reported as the median value, and statistical comparisons between median mutation rates were performed using the Mann-Whitney U-test.",
    "ncbi_link": "rad52: 854976
rad59: 851500"
  },
  {
    "caption": "(A-C) Representative Southern blots showing DSB repair products (top), percentage of BIR among repair products (bottom left) and viability  (bottom right) of WT and sir2∆ in the H-150 assay (A),  H--150 no-gap assay  (B) or native mating type switching H-1400 assay (C). (mean ± SD; n = 3). Welch's unpaired t-test was used to determine the p-value in panels A-C.",
    "ncbi_link": "BIR: 853551
sir2: 851520"
  },
  {
    "caption": "(A-B) Representative Southern blots showing DSB repair products (top), percentage of BIR among repair products (bottom left) and viability (bottom right) of indicated mutants in the H-150 no-gap assay (A) or H-150 assay (B). (mean ± SD; n ≥3). Welch's unpaired t-test was used to determine the p-value in panels A and B.",
    "ncbi_link": "BIR: 853551"
  },
  {
    "caption": "(I) The MET variants by Sanger sequencing was indicated by red arrow.",
    "ncbi_link": "MET: 4233"
  },
  {
    "caption": "(J) 293T cells were transfected with FLAG-tagged MET/METMut/Vector plasmids, and 48 h post transfection, cells were treated with 10 ng/mL recombinant human HGF for 1 h. Then MET/METMut protein purification and tyrosine kinase assay were conducted. Western Blot pictures representative of n = 3 experiments. METMut means p.Y1234C mutant MET. EGFR means epidermal growth factor receptor and serves as a positive control. NC means negative control.",
    "ncbi_link": "FLAG: 
MET: 4233"
  },
  {
    "caption": "(A) In situ hybridization of E10.5 embryos using Pax3 probe. Pax3 expression (brown signal) was observed in limb bud and demomyotome (DM), respectively. Cells labeled with Pax3 were indicated by red arrow. Scale bars, 200 μm.",
    "ncbi_link": "Pax3: 18505"
  },
  {
    "caption": "(D-G) Cell death mechanisms of C3H BMDMs transfected with miR-342-3p mimic (D), or B6 BMDMs transfected with miR-342-3p inhibitor (F), followed by Mtb infection for 36 hours. Cell viabilities of C3H BMDMs transfected with miR-342-3p mimic (E), or B6 BMDMs transfected with miR-342-3p inhibitor (G), followed by stimulation with Mtb or z-VAD (20 μM) for 24 hours. Data are shown as the mean ± s.e.m. of n = 3 biological replicates.",
    "ncbi_link": "miR-342-3p: 723909"
  },
  {
    "caption": "(A, B) Survival of Mir342+/+C3H mice and their wild-type littermate controls (C3H) (n=10) (A), or Mir342-/-B6 mice and their wild-type littermate controls (B6) (n=10) (B) after aerosol infection with around 400 CFU Mtb. Data are shown as the Kaplan-Meier curves.",
    "ncbi_link": "Mir342: 723909"
  },
  {
    "caption": "(G, H) Secretion of cytokines TNF-α, IL-1, IL-6 and CXCL15 in BMDMs obtained from Mir342+/+C3H and their littermates (C3H) (G), or from Mir342-/-B6 and their littermates (B6) (H) after Mtb stimulation, was detected by ELISA. Data are shown as the mean ± s.e.m. of n = 3 biological replicates.",
    "ncbi_link": "Mir342: 723909"
  },
  {
    "caption": "(C, D) MiR-342-3p mimic or inhibitor was transfected to NIH-3T3 fibroblasts. After 48 hours, cells were collected for qRT-PCR (C, data are shown as the mean ± s.e.m. of n = 3 biological replicates) and western blotting (D, representative blots from n = 3 biological replicates are shown) to detect SOCS6 expression.",
    "ncbi_link": "MiR-342-3p: 723909"
  },
  {
    "caption": "(F-H) C3H BMDMs were transfected with miR-342-3p mimic or SOCS6-overexpressing lentivirus, followed by stimulation with Mtb or z-VAD (20 μM) for 24 hours. Cell death mechanisms (F), cell viabilities (G) and Mtb growth rates (H) were analyzed respectively. Data are shown as the mean ± s.e.m. of n = 3 biological replicates.",
    "ncbi_link": "miR-342-3p: 723909
SOCS6: 54607"
  },
  {
    "caption": "(A, B) Survival of Mir342-/-B6 and Mir342-/-B6 mice supplemented with Socs6 siRNA (n=10) (A), or Mir342+/+C3H and Mir342+/+C3H mice supplemented with SOCS6-overexpressing vector (n=10) (B), after aerosol infection with around 400 CFU Mtb. Data are shown as the Kaplan-Meier curves.",
    "ncbi_link": "Mir342: 723909
Socs6: 54607
SOCS6: 54607"
  },
  {
    "caption": "(C-F) Relative expressions of chemokines CCL5, CXCL10, ICAM1 (C), and Caspase 3, Caspase 7, Caspase 8 (F) in Mtb-stimulated Socs6+/+ or Socs6-/- BMDMs were detected by qRT-PCR. Data are shown as the mean ± s.e.m. of n = 3 biological replicates. Cluster analysis of clinical samples.",
    "ncbi_link": "Caspase 3: 12367
Caspase 7: 12369
Caspase 8: 12370
CCL5: 20304
CXCL10: 15945
ICAM1: 15894
Socs6: 54607"
  },
  {
    "caption": "(C) Socs6-/- BMDMs were transfected with plasmids expressing Myc-RIPK3 or Myc-RIPK3 K51A mutant for 24 hours. Afterwards, transfected cells were stimulated with Mtb for 12 hours, cell lysates were collected and immunoprecipitated using an anti-RIPK1 antibody. The recruitment of Caspase 8, RIPK3, FADD and MLKL was analyzed by immunoblot. The lower panel represents the immunoblot analysis of whole cell lysates. Representative blots from n = 3 biological replicates are shown.",
    "ncbi_link": "Myc: 
RIPK3: 56532
Socs6: 54607"
  },
  {
    "caption": "(D-F) Cell viabilities (D), cell death mechanisms (E), or Mtb growth rates (F) of Mtb-infected Socs6-/- BMDMs that were transfected with plasmids expressing Myc-RIPK3 or Myc-RIPK3 K51A mutant as indicated. Z-VAD treatment concentration was 20 μM and the treatment time was 24 hours. Data are shown as the mean ± s.e.m. of n = 3 biological replicates.",
    "ncbi_link": "Myc: 
RIPK3: 56532
Socs6: 54607"
  },
  {
    "caption": "(E-G) RAW264.7 cells were transfected with plasmids expressing A20 and RIPK3 (E), or A20 and RIPK3 mutants (G) as indicated, cell lysates were collected for immunoprecipitation and immunoblot. Myc-A20 or Flag-RIPK3 purified from transfected HEK-293T cells was incubated with ATP, E1, E2 and ubiquitin as indicated. The in vitro ubiquitination of RIPK3 was analyzed by immunoblot using an anti-Ub antibody (F). Representative blots from n = 3 biological replicates are shown.",
    "ncbi_link": "RIPK3: 56532
A20: 21929"
  },
  {
    "caption": "(A, B) Production of cytokines TNF-α, IL-1, IL-6, CXCL15 (A), or chemokines Ccl5, Cxcl10, Icam1 (B) in the A20-/-Socs6+/+, A20+/+Socs6+/+, A20-/-Socs6-/- and A20+/+Socs6-/- BMDMs after Mtb stimulation. Data are shown as the mean ± s.e.m. of n = 3 biological replicates.",
    "ncbi_link": "Ccl5: 20304
Cxcl10: 15945
Icam1: 15894
Socs6: 54607
A20: 21929"
  },
  {
    "caption": "(A, B) Two-dimensional tryptic mapping of YFP-p27, YFP-p27T198A and a mixture of both (A). Phosphoamino-acid analysis of spots a and b (B). The migration of phosphoserine (S), phosphothreonine (T) and phosphotyrosine (Y) is marked with circles in B. The asterisk indicates the origin of migration.",
    "ncbi_link": "p27: 1027"
  },
  {
    "caption": "(C-E) MCF-7 transfected with YFP-p27 or YFP-p27T198A mutant (C, D) or cotransfected with YFP-p27 and an empty RFP vector in a 5:1 (YFP-p27: RFP) ratio (E) were treated with (+) or without (−) MG132 (10 μM) for 12 h before western blot analysis (C) and fluorescence microscopy (D, E).",
    "ncbi_link": "p27: 1027
p27T198A: 1027"
  },
  {
    "caption": "(C-E) MCF-7 transfected with YFP-p27 or YFP-p27T198A mutant (C, D) or cotransfected with YFP-p27 and an empty RFP vector in a 5:1 (YFP-p27: RFP) ratio (E) were treated with (+) or without (−) MG132 (10 μM) for 12 h before western blot analysis (C) and fluorescence microscopy (D, E).",
    "ncbi_link": "p27: 1027
p27T198A: 1027"
  },
  {
    "caption": "(F) Western blots of protein extracts from MCF-7 transfected with YFP-p27, YFP-p27T198A or YFP-p27T198D mutants following incubation with cycloheximide (CHX) for the indicated times. Uncropped images of the blots are shown in the Supplementary Information, Fig. S5.",
    "ncbi_link": "p27: 1027
p27T198A: 1027"
  },
  {
    "caption": "(a) Crystal violet staining of MCF-7 cell transfected with YFP (C1), YFP-p27, YFP-p27T198A or YFP-p27T198D and selected with G418 for three weeks. Data are presented as mean ± s.d. (n = 3).",
    "ncbi_link": "p27: 1027"
  },
  {
    "caption": "(b) Flow cytometry analysis of MCF-7 cells transfected with YFP (C1) or YFP-p27, YFP-p27T198A and YFP-p27T198D for 48 h. Data are presented as mean ± s.d. (n = 3).",
    "ncbi_link": "p27: 1027"
  },
  {
    "caption": "(c) GFP-LC3 U2OS cells 48 h post-transfection with RFP, RFP-p27, RFP-p27T198A or RFP-p27T198D. Data represent results of three independent experiments, from which a total of ∼200 cells were counted (s.d., 10∼15%). The scale bars represent 50 μm in c.",
    "ncbi_link": "p27: 1027
LC3: 440738///81631///84557"
  },
  {
    "caption": "(c) MCF-7 cells were transfected with vector alone (C1), YFP-p27 (WT), or the siRNA-resistant constructs WT-R and T198A-R 24 h before RNA interference (RNAi). PARP cleavage was determined by western blotting and densitometric scanning. Data represent three independent experiments (mean ± s.d.).",
    "ncbi_link": "p27: 1027"
  },
  {
    "caption": "(e) MCF-7 cells treated with or without LY294002 for 48 h following RNAi. p27 siRNA pool-1, siRNA1, 2 and 3; arrows, membrane blebbing; triangles, apoptotic bodies. The scale bar represents 50 μm.",
    "ncbi_link": "p27: 1027"
  },
  {
    "caption": "(c) Western blots of protein lysates from Hela cells transfected with either pCDNA3 or wild-type LKB1 cultured with or without glucose for 24 h.",
    "ncbi_link": "LKB1: 6794"
  },
  {
    "caption": "(A) FACS analysis of TUNEL positive p27+/+ and p27−/− cells treated with AICAR for 20 h. Data represent mean ± s.d. of three independent experiments.",
    "ncbi_link": "p27: 12576"
  },
  {
    "caption": "(B, C) Electron microscopy of p27+/+ (a, c and e) and p27−/− (b, d and f) MEFs treated with (c and d), or without (a and b) AICAR (1 mM), or without glucose (e and f) for 14 h. Magnified images of the boxed areas were shown on the left (a′, b′, c′, d′, e′ and f′) with arrowheads indicating autophagic vacuoles including autolysosomes (black arrowheads). The scale bars represent 10 μm in a-f and 0.5 μm in a′-f′. N, nucleus. Autophagic vacuoles were counted for three randomly selected cells from each electron microscopy section and data represent mean ± s.d. (C).",
    "ncbi_link": "p27: 12576"
  },
  {
    "caption": "(B, C) Electron microscopy of p27+/+ (a, c and e) and p27−/− (b, d and f) MEFs treated with (c and d), or without (a and b) AICAR (1 mM), or without glucose (e and f) for 14 h. Magnified images of the boxed areas were shown on the left (a′, b′, c′, d′, e′ and f′) with arrowheads indicating autophagic vacuoles including autolysosomes (black arrowheads). The scale bars represent 10 μm in a-f and 0.5 μm in a′-f′. N, nucleus. Autophagic vacuoles were counted for three randomly selected cells from each electron microscopy section and data represent mean ± s.d. (C).",
    "ncbi_link": "p27: 12576"
  },
  {
    "caption": "(E) Validation of the binding specificity for the Hippo WW domain-containing proteins. HEK293T cells were transfected with the indicated SFB-tagged constructs and subjected to the pulldown assay.",
    "ncbi_link": "SFB: "
  },
  {
    "caption": "(F) Validation of the binding specificity for the derived WW domains from the Hippo WW domain-containing proteins. HEK293T cells were transfected with the indicated SFB-tagged constructs and subjected to the pulldown assay.",
    "ncbi_link": "SFB: "
  },
  {
    "caption": "(C-G) Validation of the identified 9-amino acid sequence in determining the Hippo WW domain binding specificity. The requirement of the identified 9-amino acid sequence for AMOT association was respectively examined for TAZ (C), TAZ-WW domain (D), KIBRA (E), YAP (F) and SAV1 (G). HEK293T cells were transfected with the indicated SFB-tagged constructs and subjected to the pulldown assay.",
    "ncbi_link": "SFB: "
  },
  {
    "caption": "(C) The identified 9-amino acid sequence is required for the association between STXBP4 and AMOT. HEK293T cells were transfected with the indicated STXBP4 mutants and subjected to the pulldown assay.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(F) Loss of STXBP4 inhibits YAP phosphorylation and LATS activation. Western blotting was performed with the indicated antibodies.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "Loss of STXBP4 activates YAP. STXBP4 deficiency promotes YAP nuclear translocation (G)",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "Loss of STXBP4 activates YAP. STXBP4 deficiency promotes YAP downstream gene transcription (mean ± s.d., n=3 biological replicates) (H). Scale bar, 20 μm.*** p < 0.001 (Student's t-test).",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(I) WW domain is required for the STXBP4-mediated YAP cytoplasmic translocation. STXBP4 KO cells were transfected with the indicated STXBP4 constructs and immunofluorescent staining was performed. HA-positive cells (arrows) from ~30 different views (~200 cells in total) were randomly selected and quantified for YAP localization. Percentage of HA-positive cells with nuclear YAP enrichment is shown. Scale bar, 20 μm.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(J) Loss of STXBP4 attenuates YAP phosphorylation as induced by actin cytoskeleton inhibition. The indicated cells were subjected to serum starvation (treatment with no-serum medium for 12 hours), glucose starvation (treatment with no-glucose medium for 6 hours) or actin inhibition (treatment with 0.5 μg/mL latrunculin B or 5 μM blebbistatin for 30 min). YAP phosphorylation was detected using phospho-tag gel, where the YAP phosphorylation level was indicated.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(C) STXBP4 promotes the association of α-catenin with AMOT and LATS1. HEK293T cells were transfected with the indicated SFB-tagged constructs and subjected to the pulldown assay.",
    "ncbi_link": "SFB: 
STXBP4: 252983"
  },
  {
    "caption": "(D) Loss of STXBP4 diminishes the association of α-catenin with AMOT, LATS1 and YAP. HEK293A and STXBP4 KO cells were transfected with the SFB-tagged α-catenin construct and subjected to the pulldown assay.",
    "ncbi_link": "SFB: 
α-catenin: 29119///1496///1495
STXBP4: 252983"
  },
  {
    "caption": "(E) STXBP4 induces the co-localization between α-catenin and AMOT as well as LATS1 and YAP. HEK293A cells were transfected with the indicated constructs and immunofluorescence was performed. Scale bar, 20 μm.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "Identification of several STXBP4 missense mutations that disrupt its interaction with α-catenin and AMOT. The identified missense mutations respectively disrupted the STXBP4- α-catenin (G) and STXBP4-AMOT (H) complex formation.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(I) Inhibition of actin cytoskeleton promotes the STXBP4-associated protein complex formation. HEK293A and the STXBP4 KO cells were subjected to immunoprecipitation using pre-immune serum and anti-STXBP4 serum under the indicated treatments.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(J) The missense mutations of STXBP4 (F) diminished the ability of STXBP4 to rescue YAP phosphorylation in the STXBP4 KO cells with low actin cytoskeleton tension. YAP phosphorylation was detected using phospho-tag gel, where the YAP phosphorylation level was indicated.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "STXBP4 is downregulated in human kidney cancer. The mRNA level of STXBP4 is analyzed in the Firebrowse web database (A), where 14,729 tumor sample data generated by TCGA were included. The first quartile, median and third quartile values were indicated as the boxplots. Outliers were plotted as individual points. Error bars indicated the standard deviation above and below the mean of the data.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "STXBP4 is downregulated in human kidney cancer. The expression of STXBP4 was also examined using kidney tissue microarray, where percentage of the indicated tissue samples with downregulated STXBP4 was shown (B). The p value was calculated by using the paired Student's t-test.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(C) Kaplan-Meier curves of overall survival of patients with ccRCC is stratified by STXBP4 expression level. Clinical data of STXBP4 were analyzed in TCGA-KIRC project containing total 611 patient samples. The p value was calculated by using the Log-rank (Mantel-Cox) test.",
    "ncbi_link": "STXBP4: 252983"
  },
  {
    "caption": "(G and H) Both the association with α-catenin and the functional WW domain are required for the STXBP4's tumor suppressive function in 786-O cells. Overexpression of STXBP4, but not the indicated STXBP4 missense mutants, significantly suppressed the 786-O cell xenograft tumor formation. Xenograft tumors are shown in (G), and the tumor weight is quantified in (H) (n = 5 mice, mean ± s.d.). ** p < 0.01 (Student's t-test). Scale bar, 1 cm.",
    "ncbi_link": "α-catenin: 1495///1496///29119
STXBP4: 252983"
  },
  {
    "caption": " A TUNEL assay comparing apoptotic cells in Miwi+/- and Miwi-/- testis during diakinesis. Blue, DAPI; Green, TUNEL labeling. Asterisk indicates TUNEL-positive stained cells in the meiotic metaphase stage. Scale bars, 10 μm. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " B, C Meiotic metaphase I plate in FACS-sorted Miwi heterozygous (B) and knockout (C) spermatocytes. Green: phospho-histone H3; red: α/β-tubulin. Asterisk indicates misaligned chromosome. Scale bars, 10 μm. D Frequency of abnormal arrangement in the meiotic metaphase I plate. White, Miwi heterozygous; Light gray, Miwi knockout. Three mice were used for each genotype, total numbers of counted metaphase I plate in Miwi heterozygous and knockout are 113 and 181, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " E, F Meiotic metaphase II spread preparations of Miwi heterozygous (E) and knockout (F) spermatocytes. Scale bars, 5 μm. G Frequency of meiotic metaphase II (MII) cells with chromosomal abnormalities. Chromosome counts were defined as the number of paired sister chromatids per MII metaphase cell. The frequency was calculated as the number of cells with given pairs of sister chromatids (20, <20, or >20) divided by the total number of cells. Three mice were used for each genotype, total numbers of counted MII cells in Miwi heterozygous and knockout are 204 and 302, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " H, I Meiotic metaphase I spread preparations of Miwi heterozygous (H) and knockout (I) spermatocytes. Scale bars, 5 μm. J Frequency of meiotic metaphase I (MI) cells with chromosomal abnormalities. Chromosome counts were defined as the number of paired homologous chromosomes per MI metaphase cells. The frequency was calculated in the same way as in (G), except for that the number of paired chromosomes was counted instead. Three mice were used for each genotype, total numbers of counted MI cells in Miwi heterozygous and knockout are 265 and 358, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": "K, L Mitotic metaphase spread preparations of Miwi heterozygous (K) and knockout (L) testes. Scale bars, 5 μm. M Frequency of mitotic metaphase cells with chromosomal abnormalities. Chromosome counts were defined as the number of chromosomes per mitotic metaphase cell. Three mice were used for each genotype, total numbers of counted mitotic metaphase cells in Miwi heterozygous and knockout are 52 and 71, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " A Equal amounts of total RNA isolated from Miwi knockout (-/-), heterozygote (+/-) and slicer activity-deficient mutant (-/ADH) spermatocytes, were resolved on a 1% agarose gel. The gel was subjected to northern blot analysis using probes specific for the sense (S) and antisense (As) strands of major (Maj) and minor (Min) satellite RNA transcripts. The blot was re-hybridized with a 28S-complementary probe to demonstrate equal loading (bottom on the left). The relative abundance was quantified using ImageJ software, normalized to the 28S signal from the blot. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " B 100ng of total RNA was isolated from Miwi heterozygous (+/-), knockout (-/-) and slicer activity-deficient mutant (-/ADH) spermatocytes and was subjected to qRT-PCR with primers specific to major satellite RNA, minor satellite RNA, 5S, 5.8S and Gapdh. Data were normalized to 5S rRNA. 5.8S rRNA and Gapdh were used as negative controls.",
    "ncbi_link": "Gapdh: 14433
Miwi: 57746"
  },
  {
    "caption": "Sertoli-spermatogenic cell co-cultures were transfected with vectors ectopically expressing both strands of major satellite RNA (Maj, dark gray bar), both strands of minor satellite RNA (Min, black bar), full-length 18S (18S, light gray bar) or empty vector (Ctrl, white bar). Total RNA isolated from equal numbers of FACS-sorted MIWI-expressing spermatocytes were subjected to qRT-PCR with primers specific to major satellite RNA (C), minor satellite RNA (D), 18S (E)",
    "ncbi_link": "MIWI: 57746"
  },
  {
    "caption": " Sertoli-spermatogenic cell co-cultures were transfected with vectors ectopically expressing both strands of major satellite RNA (Maj, dark gray bar), both strands of minor satellite RNA (Min, black bar), full-length 18S (18S, light gray bar) or empty vector (Ctrl, white bar). Total RNA isolated from equal numbers of FACS-sorted MIWI-expressing spermatocytes were subjected to qRT-PCR with primers specific to 5.8S (F) and Gapdh (G). Data presented were normalized to 5S rRNA. 5.8S rRNA (F) and Gapdh (G) were used as negative controls. ",
    "ncbi_link": "Gapdh: 14433
MIWI: 57746"
  },
  {
    "caption": " I Frequency of mis-arrangement of the meiotic metaphase I plate in Sertoli-spermatogenic cell cocultures using Miwi+/-;Stra8-Cre testes. Spermatocytes transfected with vectors expressing both strands of major satellite RNA (Maj, dark gray), both strands of minor satellite RNA (Min, black), full-length 18S (18S, light gray) or empty vector (Ctrl, white). n=3 cultures for each group. The total numbers of counted meiotic metaphase plate in Ctrl, 18S, Maj and Min were 153, 144, 130 and 141, respectively. ",
    "ncbi_link": "Cre: 2777477
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": " J Combined RNA-DNA FISH analysis of major satellite transcripts and DNA regions in Miwi heterozygote (Miwi+/-) and knockout (Miwi-/-) diakinesis spermatocytes. Sense major satellite RNA transcripts were first detected using an antisense probe (red signal), and then the major satellite DNA region was further detected using a sense probe (green signal). For RNase A treatment, the slides were incubated with (+RNase A) or without (-RNase A) 100 μg/ml RNase A for 1 hour before adding antisense probe. Nuclear DNA was stained by DAPI (blue). Arrows indicate the same pericentric heterochromatin in each channel per cell. Scale bars represent 2 µm. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " A Combined immunofluorescence and DNA FISH analysis of the kinetochore inner plate/centromere formation in Miwi heterozygous (Miwi+/-) and knockout (Miwi-/-) spermatocytes at diakinesis/metaphase I. For slicer activity-deficient mutant spermatocytes (Miwi-/ADH), the images are presented in Fig EV1A. Chromosomes were stained with anti-centromere protein antibody (CREST, purple signal), indicating the kinetochore inner plate/centromere. Major satellite DNA regions were detected using an antisense probe (red signal) which revealed the specific localization of pericentromeres in chromosomes. Nuclear DNA was stained by DAPI (blue). Scale bars represent 2 µm. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " B Left panel: illustration of kinetochore configurations in meiotic metaphase I. The kinetochores of sister chromatids cohere to form a single microtubule-binding interface. The inner-outer kinetochore axis connects the pericentric chromatin to the spindle microtubule. CREST (centromere protein) and BUBR1 (budding uninhibited by benzimidazole-related 1) served as markers for the inner and outer regions of the kinetochore, respectively. A major satellite DNA (Maj sat DNA) probe was used to detect the pericentric chromatin. Right panel: categories of inner kinetochore configurations from A. Right panels: Inner kinetochore configurations in MI were classified as overlapping (two sister kinetochores which overlap by more than their individual radii, also see yellow arrow in A), adjacent (two sister kinetochores which overlap by less than 100% of their individual radii, also see magenta arrow in A) or separated (two sister kinetochores without overlapping, also see light blue arrow in A) kinetochores. The scale bar represents 1 µm. C Population of overlapping, adjacent, and separated inner kinetochores shown in B. The results represent the mean ± SD of three independent experiments. n=3 mice for each genotype. The total numbers of counted cells in Miwi+/-, Miwi-/- and Miwi-/ADH spermatocytes were 88, 118 and 125, respectively. The total numbers of counted sister kinetochore pairs in Miwi+/-, Miwi-/- and Miwi-/ADH spermatocytes were 3,520, 4,720 and 5,000, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": " D Combined immunofluorescence and DNA FISH analysis of kinetochore inner and outer plate formation in Miwi heterozygous (Miwi+/-) and knockout (Miwi-/-) at diakinesis/metaphase I. For slicer activity-deficient mutant spermatocytes (Miwi-/ADH), the images are presented in Fig EV1B. Chromosomes were stained with anti-BUBR1 (green) and anti-centromere-protein (CREST, purple) antibodies to mark the kinetochore outer and inner plate, respectively. In addition, major satellite DNA regions were further detected using an antisense probe (red signal). Nuclear DNA was stained by DAPI (blue). O-O kinetochore pairs: yellow arrow; S-S, magenta arrow; O-S, light blue arrow; and S-O, light green arrow. Scale bars represent 2 µm. E Magnified images of categories of sister kinetochore configurations from D. One arrow indicates overlapping pair. Double arrows indicate split pair. The scale bar represents 1 µm. F Population of the sister kinetochores shown in E. n=3 mice for each genotype. The total numbers of counted cells in Miwi+/-, Miwi-/- and Miwi-/ADH spermatocytes were 93, 89 and 81, respectively. The total numbers of counted sister kinetochore pairs in Miwi+/-, Miwi-/- and Miwi-/ADH spermatocytes were 3,720, 3,560 and 3,240, respectively. ",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": "B RNA pull-down assay using biotinylated major and minor satellite RNA transcripts and whole cell extracts from Miwi heterozygoous (Miwi+/-), knockout (Miwi-/-), slicer activity-deficient mutant (Miwi-/ADH), and Mov10l1 germline knockout (Mov10l1f/-;Stra8-Cre) testes. Mov10l1f/-;Stra8-Cre mice represent a pachytene piRNA-deficient condition. Approximately one repeat of In vitro transcribed major and minor satellite RNAs corresponding to the sequences in A were used as baits. Precipitated proteins were visualized by Western blotting using antibodies against the indicated proteins (MIWI and MILI). The input equals 1/10 to 1/80 of the protein lysate used in the pull-down. Transcripts corresponding to 300 nt and 162 nt of the 18S rRNA sequence served as controls for the antisense (As) and sense (S) sequence of major and minor satellite transcripts, respectively. The blot was re-probed with anti-GAPDH antibody serving as a negative control.",
    "ncbi_link": "Cre: 2777477
Mov10l1: 83456
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": "C In vitro RNA processing assay with nuage-nuclear fraction from testicular lysates of Miwi knockout (-/-), heterozygous (+/-), and slicer activity-deficient (-/ADH) mutants, and 5'-end radioactively labelled RNA targets corresponding to approximately one and two repeats of major and minor satellite sequences (see panel A for details). Transcripts corresponding to 162, 300, and 542 nt of the 18S rRNA sequence served as controls. Arrow indicates the cleavage products of In vitro transcribed sense major satellite RNAs after reactions.",
    "ncbi_link": "Miwi: 57746"
  },
  {
    "caption": "D In vitro RNA processing assay with nuage-nuclear fraction from Mov10l1 heterozygous (Mov10l1f/+;Stra8-Cre) and Mov10l1 germline knockout (Mov10l1f/-;Stra8-Cre) testis lysates, and 5'-end radioactively labelled RNA targets corresponding to approximately one and two repeats of sense and antisense major satellite sequences. Mov10l1f/-;Stra8-Cre mice represent a pachytene piRNA-deficient condition. The arrow indicates the cleavage product of the in vitro transcribed sense major satellite RNA.",
    "ncbi_link": "Cre: 2777477
Mov10l1: 83456
Stra8: 20899"
  },
  {
    "caption": "RNA-immunoprecipitation was performed using anti-MIWI antibody. RNA was extracted from anti-MIWI immunoprecipitates and subjected to Northern blot analysis using probes specific for potential piRNAs (piR major-a and b), as indicated in panel 20% of input RNA from each group was used as the control. The blot was re-hybridized with piR-A and piR-E complementary probes to demonstrate the efficiency of the RNA-IP. A miR-16 complementary probe served as a negative control.",
    "ncbi_link": "piR-A: 
piR-E: 
miR-16: 723949///387134
MIWI: 57746"
  },
  {
    "caption": " A RNA pull-down was performed using in vitro transcribed biotinylated transcripts and whole cell extracts from Miwi+/-, Miwi-/-, Miwi-/ADH, and Mov10l1f/-;Stra8-Cre testes. Mov10l1f/-;Stra8-Cre mice represent a pachytene piRNA-deficient condition. In vitro transcribed RNAs corresponding to approximately one repeat of major and minor satellite sequences were used as baits. Precipitated protein was visualized by Western blotting using anti-Dicer antibody. ",
    "ncbi_link": "Cre: 2777477
Mov10l1: 83456
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": " B Equal amounts of total RNA isolated from spermatocytes of Miwi+/-;Dicerf/+;Stra8-Cre, Miwi-/-;Dicerf/+;Stra8-Cre, Miwi+/-;Dicerf/-;Stra8-Cre and Miwi-/-;Dicerf/-;Stra8-Cre mice, were resolved on a 1% agarose gel. The gel was subjected to Northern blot analysis using probes specific for the sense and antisense sequences of major and minor satellites. The blot was re-hybridized with a 28S rRNA-complementary probe to demonstrate equal loading (bottom on the left). ",
    "ncbi_link": "Cre: 2777477
Dicer: 192119
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": " C in vitro RNA processing assay with nuage-enriched nuclear fraction from Miwi+/-;Dicerf/+;Stra8-Cre, Miwi-/-;Dicerf/+;Stra8-Cre, and Miwi+/-;Dicerf/-;Stra8-Cre mice, and 5'-end radioactively labelled RNA targets corresponding to approximately one and two repeats of sense and antisense major satellite sequences. Arrow indicates the cleavage products of In vitro transcribed sense major satellite RNAs by MIWI-piRNA complex. ",
    "ncbi_link": "Cre: 2777477
Dicer: 192119
MIWI: 57746
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": " D Equal amounts of total RNA isolated from spermatocytes of Miwi+/-;Dicerf/+;Stra8-Cre, Miwi-/-;Dicerf/+;Stra8-Cre, Miwi+/-;Dicerf/-;Stra8-Cre and Miwi-/-;Dicerf/-;Stra8-Cre mice, were digested with RNase III (RNase III) or nuclease S1 (S1), and further resolved on a 1% agarose gel. The gel was subjected to northern blot analysis using probes specific for the sense (S) and antisense (As) strands of major (Maj) and minor (Min) satellite transcripts. The blot was re-hybridized with 18S and 28S-complementary probes to demonstrate equal loading and the same efficiency of RNase III or nuclease S1 digestion. ",
    "ncbi_link": "Cre: 2777477
Dicer: 192119
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": " E Sequential in vitro RNA processing assay using 5'-end radioactively labelled RNA targets corresponding to approximately one repeat of sense and antisense major satellite sequences. The nuage-nuclear fraction from Miwi+/- testes is indicated as N. Total cellular extracts (T) from Miwi+/- testes were subjected to immunodepletion using anti-Dicer antibodies (α-Dicer), with IgG (IgG ) as a negative control. The incubation time (Incub. t) was 0.5 and 1 hour. The arrow indicates the product of MIWI-mediated cleavage of the in vitro transcribed sense major satellite RNA.",
    "ncbi_link": "Miwi: 57746
MIWI: 57746"
  },
  {
    "caption": " A Frequency of overlapping, adjacent, and separated inner kinetochores. Spermatocytes from Miwi+/-;Dicerf/+;Stra8-Cre, Miwi-/-;Dicerf/+;Stra8-Cre, Miwi+/-;Dicerf/-;Stra8-Cre, and Miwi-/-;Dicerf/-;Stra8-Cre mice were used to examine sister kinetochore configuration at meiosis I as shown in Fig 3A and 3B. n=3 mice for each genotype. The total numbers of counted cells in the four types of spermatocytes were 101, 117, 129 and 115, respectively. The total numbers of counted sister kinetochore pairs in the four types of spermatocytes were 4,040, 4,680, 5,160 and 4,600, respectively. B Frequency of the different sister kinetochore configurations. The four types of spermatocytes in A were used to examine sister kinetochore configurations in meiosis I metaphase with O-O, S-S, O-S, or S-O as defined in the text. n=3 mice for each genotype. The total numbers of counted cells in the four types of spermatocytes were 134, 140, 140 and 130, respectively. The total numbers of counted sister kinetochore pairs in the four types of spermatocytes were 5,360, 5,600, 5,600 and 5,200, respectively. ",
    "ncbi_link": "Cre: 2777477
Dicer: 192119
Miwi: 57746
Stra8: 20899"
  },
  {
    "caption": "B) AWA-laser-ablated males were not attracted by the sex pheromone in single-worm chemoattraction assays. Both AWA-defective mutant males (lin-11 and odr-7) and AWA-laser-ablated males failed to reach the sex pheromone within 30 min. Wild-type C. elegans males responded normally to the sex pheromone and wild-type C. elegans hermaphrodites were not attracted by same-sex pheromone. The single-worm chemoattraction assay was performed as described in Materials and Methods. Sample size of males in AWA-laser-ablation experiment: 12; all other experiments: 100 worms.",
    "ncbi_link": "lin-11: 172893
odr-7: 181403"
  },
  {
    "caption": "C) In males from both AWA-specific-rescue odr-3 mutant strain and odr-3 rescued mutant strain, the sex pheromone response was significantly restored in single male worm arrival assays. However, males from the CEM-specific-rescue odr-3 mutant strain failed to reach the sex pheromone within 30 min. In odr-3 and him-5 strain experiments, the sample sizes were 12 and 20 worms, respectively; in all other experiments, 40 worms were used.",
    "ncbi_link": "him-5: 183932
odr-3: 179806"
  },
  {
    "caption": "A) srd-1 mutant males were not attracted to the sex pheromone but were attracted to the positive-control chemoattractants, 1:1000 diacetyl and 10 mg/mL pyrazine. This demonstrated that SRD-1 is required and specific for sex pheromone perception. Data information: For each transgenic strain, 3 independent lines were examined. We assayed 400 males from each strain in the sex pheromone chemoattraction assay. Two biological replicates were combined into a single value. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Means ± SEM (error bars) are shown.",
    "ncbi_link": "srd-1: 191794
SRD-1: 191794"
  },
  {
    "caption": "B) Summary of srd-1 expression pattern. The transcriptional reporter Psrd-1::gfp was detected in both male and hermaphrodite ASI neurons in the head region, and only in male AWA and ADF neurons.",
    "ncbi_link": "gfp: 
srd-1: 191794"
  },
  {
    "caption": "C) SRD-1::GFP fusion construct revealed predominant SRD-1 localization at the cilia of AWAs in C. elegans males. Scale bar = 5 μm.",
    "ncbi_link": "GFP: 
SRD-1: 191794"
  },
  {
    "caption": "D) Examination of srd-1 transcriptional reporter revealed that srd-1 is expressed in AWA neurons in males but not hermaphrodites. A transcriptional reporter for odr-7 indicated the locations of AWAs (arrowheads). Scale bar = 50 μm.",
    "ncbi_link": "srd-1: 191794"
  },
  {
    "caption": "F) AWA-specific rescue of srd-1 restored sex pheromone perception ability in both males and hermaphrodites. Data information: For each transgenic strain, 3 independent lines were examined. We assayed 400 males from each strain in the sex pheromone chemoattraction assay. Two biological replicates were combined into a single value. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Means ± SEM (error bars) are shown.",
    "ncbi_link": "srd-1: 191794"
  },
  {
    "caption": "G) Ectopic expression of srd-1 in AWB neurons elicited a distinct repulsive behavior toward the sex pheromone in both males and hermaphrodites. Data information: For each transgenic strain, 3 independent lines were examined. We assayed 400 males from each strain in the sex pheromone chemoattraction assay. Two biological replicates were combined into a single value. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Means ± SEM (error bars) are shown.",
    "ncbi_link": "srd-1: 191794"
  },
  {
    "caption": "C) Relative fluorescence-intensity change was quantified through calcium imaging. Wild-type males showed receptor excitation by sex pheromones from C. elegans hermaphrodites or C. remanei females. This response was lost in srd-1-mutant-strain males but was restored following AWA-specific rescue of srd-1. Red triangles: time points of sex pheromone addition. Three males were assayed from each strain.",
    "ncbi_link": "srd-1: 191794"
  },
  {
    "caption": "C) Expression level of srd-1 cDNA in srd-1 transgenic lines. srd-1 mutant males were rescued using, separately, wild-type C. elegans and wild-type C. remanei srd-1 cDNAs. Transgenic lines expressing the molecule at a similar level were selected for use in chemoattraction assays. Four independent transgenic lines were selected, and the expression-level data were combined into a single bar. The expression levels were measured using qPCR. Data information: For transgenic-line studies, each bar represents a total of 1200 males from 4 independent transgenic lines; 20 assays were performed for 2 independent transgenic lines and 10 assays were performed for the other 2 independent transgenic lines, and the tests were conducted over 2-4 separate days. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Mean ± SEM (error bars) are shown.  ",
    "ncbi_link": "srd-1: 9810098
srd-1: 191794"
  },
  {
    "caption": "D) srd-1 mutant males rescued with Ce-srd-1 cDNA showed lower responsiveness than those rescued with Cre-srd-1 cDNA, which indicates that sex pheromone perception ability depends primarily on the protein coding region and not the regulatory sequences in the promoter. The sex pheromone perception defect of srd-1 mutants was not rescued in males expressing CT-truncated SRD-1 proteins. The findings show that the CT region is essential for sex pheromone perception. Data information: We assayed 400 males from each wild-type strain in the sex pheromone chemoattraction assay. Two biological replicates were combined into a single value. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Mean ± SEM (error bars) are shown.  ",
    "ncbi_link": "srd-1: 9810098
srd-1: 191794
SRD-1: 191794"
  },
  {
    "caption": "E) srd-1 mutant males rescued by using Ce-srd-1 cDNA together with Cre-srd-1 CT cDNA were more responsive to sex pheromone than those rescued using Cre-srd-1 cDNA with Ce-srd-1 CT cDNA. The results of the CT-swapping experiment demonstrated that sex pheromone perception ability is determined by the CT region and not the rest of the SRD-1 protein. Data information: We assayed 400 males from each wild-type strain in the sex pheromone chemoattraction assay. Two biological replicates were combined into a single value. Significance was determined using one-way ANOVA with Bonferroni correction: ***P<0.001. Mean ± SEM (error bars) are shown.  ",
    "ncbi_link": "srd-1: 9810098
srd-1: 191794
SRD-1: 191794"
  },
  {
    "caption": "Mean ± SEM CB2 mRNA levels in cerebellar extracts of WT and ASM-KO mice (n = 5 mice per group).",
    "ncbi_link": "CB2: 12802
ASM: 100340"
  },
  {
    "caption": "Western blot against CB2 and PSD-95 (used as loading control) and graph showing mean ± SEM CB2 protein levels in cerebellar extracts of WT and ASM-KO mice (n = 6 mice per group).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM CB1 mRNA levels in cerebellar extracts of WT and ASM-KO mice (**P = 0.0013, n = 6 mice per group, Student's t-test).",
    "ncbi_link": "CB1: 12801
ASM: 100340"
  },
  {
    "caption": "Western blot against CB1 and GAPDH (used as loading control) and graph showing mean ± SEM CB1 protein levels in cerebellar extracts of WT and ASM-KO mice (n = 3 mice per group).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence images against CB1 and the following cellular markers: Calbindin for Purkinje cells (E), GFAP for astrocytes (F) and F4/80 for microglia (G) in the cerebellum of WT and ASM-KO mice. DAPI stains cell nuclei. Graphs to the left show mean ± SEM intensity associated to CB1 in the Purkinje cells (shown by white arrows, E), astrocytes (F) and microglia (G) expressed as percentage of the values obtained in WT mice. Graphs to the right show the Mander's coefficient that indicates degree of co-localization between CB1 and the cellular markers for Purkinje cells (E), astrocytes (F) and microglia (G) (E: **PFluorecence intensity = 0.0082, *PMander's Coefficient = 0.0158; F: *PMander's Coefficient = 0.0115); n = 5 mice per group, Student's t-test). Scale bar, 100 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM CB1 mRNA levels in cultured hippocampal neurons from WT and ASM-KO mice (****P < 0.0001, n = 5 independent cultures, Student's t-test).",
    "ncbi_link": "CB1: 12801
ASM: 100340"
  },
  {
    "caption": "Western blot against CB1 and GAPDH (used as loading control). Images belong to the same blot but to non-consecutive lanes as indicated by the boxes. Graph showing mean ± SEM CB1 protein levels in cultured neurons from WT and ASM-KO mice (***P= 0.0009, n = 5 independent cultures, Student's t-test).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence images against CB1 and the lysosomal marker Lamp1 in cultured neurons from WT and ASM-KO mice. TOPRO stains cell nuclei. Graphs show mean ± SEM intensity associated to CB1 in the neuronal processes expressed in arbitrary units (left) or the Mander´s coefficient for the colocalization of CB1 with Lamp1 (right) (****P < 0.0001, n = 3 independent cultures, > 30 neurons per culture, Student's t-test). Scale bar, 10 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence images against CB1 and the lysosomal marker Lamp1 in Purkinje cells of the cerebellum from WT and ASM-KO mice. Graph shows mean ± SEM Mander´s coefficient indicative of the degree of colocalization of CB1 and Lamp1 (*P= 0.0213, n = 4 mice per group, Student's t-test). Scale bar, 5 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Graphs show mean ± SEM SM levels, expressed as percentage of WT values, in extracts containing the same amount of protein of cultured neurons from WT and ASM-KO mice (E)",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM CB1 mRNA levels in cultured neurons from WT mice incubated or not with 40μM SM (**P = 0.0021, n = 5 independent cultures, Student's t-test).",
    "ncbi_link": "CB1: 12801"
  },
  {
    "caption": "Mean ± SEM SM levels in cultured neurons from ASM-KO mice incubated or not with exogenous SMase (*P = 0.0157, n = 3 independent cultures, Student's t-test).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM CB1 mRNA levels in cultured neurons from ASM-KO mice incubated or not with exogenous SMase (**P= 0.0015, n = 5 independent cultures, Student's t-test).",
    "ncbi_link": "CB1: 12801
ASM: 100340"
  },
  {
    "caption": "Western blot against CB1 and GAPDH (used as loading control). Images belong to the same blot but to non-consecutive lanes as indicated by the boxes. Graph showing mean ± SEM CB1 protein levels normalized to GAPDH in extracts from cultured neurons from ASM-KO mice incubated or not with exogenous SMase (n = 5 independent cultures, Student's t-test).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence images against CB1 and the lysosomal marker Lamp1 in cultured neurons from ASM-KO mice incubated or not with exogenous SMase. DAPI stains cell nuclei. Graph shows mean ± SEM Mander´s coefficient for the colocalization of CB1 with Lamp1 (*P = 0.0189, n = 3 independent cultures, > 30 neurons per culture, Student's t-test). Scale bar, 10 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cultured neurons from ASM-KO mice treated with vehicle or with the indicated concentrations of AEA (***P<0.0001, n = 3 independent cultures, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cultured neurons from ASM-KO mice treated with vehicle, the inhibitor of NSM GW, AEA or the combination of GW and AEA (***P <0.0001, n = 3 independent cultures, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cultured neurons from ASM-KO mice treated with vehicle, or with JNJ, PF or URB in the presence or absence of AEA (**PJNJ = 0.0013, *PPF = 0.0143, ***PURB = 0.0002, **PJNJ+AEA = 0.0069, **PPF+AEA = 0.0077, ***PURB+AEA <0.0001, n = 3 independent cultures, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cultured neurons from ASM-KO mice treated with vehicle, with PF or with SR141716 + PF (*PPF = 0.0109, *PSR+PF = 0.0343, n = 3 independent cultures, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescences against the dendritic marker MAP2 of cultured neurons from ASM-KO mice treated with vehicle, AEA, JNJ, PF or URB. Scale bar, 50 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM number of apoptotic cells measured by TUNEL assays in cultured neurons from ASM-KO mice treated with H2O2 (as positive control), vehicle, AEA, JNJ, PF or URB (n = 3 independent cultures).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Weekly mean ± SEM body weight of WT and ASM-KO mice treated or not with PF (***P <0.0001, n = 7 mice per group, statistics reflect the significant difference between the slope of the data in the PF-treated ASM-KO with respect to the other three groups, Linear Regression test).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM time spent on the rod in the 4 trials of the rotarod test by WT and ASM-KO mice after two months of vehicle or PF treatment (*PT3 = 0.0488, *PT4 = 0.361, n = 4 mice per group, two - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM time spent in the new arm of the Y maze test by WT and ASM-KO mice after two months of vehicle or PF treatment (**PWTVeh Vs KO Veh = 0.0024, **PWT PF Vs KO Veh = 0.0016, *PKO PF Vs KO Veh = 0.0391, n = 9 mice per group, two - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM time of immobility in the Tail suspension test of WT and ASM-KO mice after two months of vehicle or PF treatment (*PWTVeh Vs KO Veh = 0.0198, **PWT PF Vs KO Veh = 0.0067, n = 6 mice per group, two - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM time spent in the open arms of the Elevated Plus Maze by WT and ASM-KO mice after two months of vehicle or PF treatment (*PWTVeh Vs KO Veh = 0.0342, n = 7 mice per group, two - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Percentage of survival with respect to weeks of age in WT and ASM-KO mice treated with vehicle or PF (**P = 0.0031, n = 5 mice in WT vehicle, WT PF treated and KO vehicle, 6 mice in KO PF treated, Mantel-Cox)",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM AEA levels in cerebellar extracts from WT and ASM-KO mice after two months of vehicle or PF treatment (**PWT Veh vs KO Veh = 0.0063; ****PWT Veh vs KO PF < 0.0001; ****PWT PF vs KO PF < 0.0001; ****PKO Veh vs KO PF < 0.0001, n = 4 mice per group, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cerebellar extracts from WT and ASM-KO mice after two months of vehicle or PF treatment (***PWTVeh Vs KO Veh <0.0001, *PKO Veh Vs KO PF = 0.0465), n = 4 mice per group, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Western blot against NSM and GAPDH (used as loading control) and graph showing mean ± SEM NSM protein levels in cerebellar extracts from WT and ASM-KO mice after two months of vehicle or PF treatment (n = 3 mice per group, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM CB1 mRNA levels in cerebellar extracts from WT and ASM-KO mice after two months of vehicle or PF treatment (**PWTVeh Vs KO Veh = 0.0026, *PKO Veh Vs KO PF = 0.0345), n = 4 mice per group, one - way ANOVA, Bonferroni post hoc).",
    "ncbi_link": "CB1: 12801
ASM: 100340"
  },
  {
    "caption": "Immunofluorescence against CB1 in Purkinje cells of the cerebellum of WT and ASM-KO mice after two months of vehicle or PF treatment. Graph shows mean ± SEM intensity associated to CB1, expressed as percentage of values in vehicle-treated mice (n = 4 mice per group, > 20 Purkinje cells per mouse",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence against CB1 and Lamp1 in the Purkinje cell layer of the cerebellum of WT and ASM-KO mice after two months of vehicle or PF treatment. Graphs show Mander´s coefficient for the colocalization of CB1 with Lamp1 (left) and mean ± SEM lysosomal size (right) (***PWT Veh vs. KO Veh = 0.0002; **PKO Veh vs. KO PF = 0.0052, n = 4 mice per group, >20 lysosomes per mouse, one - way ANOVA, Bonferroni post hoc). Scale bar, 5 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescence against the Purkinje cell marker Calbindin in the cerebellum of WT and ASM-KO mice after two months of vehicle or PF treatment. Graph shows mean ± SEM number of calbindin positive cells per area (***PWTVeh Vs KO Veh <0.0001, **PKO PF Vs KO Veh = 0.00642), n = 4 mice per group, one - way ANOVA, Bonferroni post hoc). Scale bar, 100 μm. Immunofluorescence against the astrocytic marker GFAP in the cerebellum of WT and ASM-KO mice after two months of vehicle or PF treatment. Graph shows mean ± SEM intensity associated to GFAP in arbitrary units (***PWTVeh Vs KO Veh < 0.0001, **PKO PF Vs KO Veh = 0.0083), n = 4 mice per group, one - way ANOVA, Bonferroni post hoc). Scale bar, 10 μm. Immunofluorescence against the microglia marker Iba1 in the cerebellum of WT and ASM-KO mice after two months of vehicle or PF treatment. Graph shows mean ± SEM number (left) and area (right) of Iba1-positive cells (Left ***PWTVeh Vs KO Veh < 0.0001, **PKO PF Vs KO Veh = 0.0034; Right ***PWTVeh Vs KO Veh < 0.0001, PKO PF Vs KO Veh = 0.00123), n = 4 mice per group, > 20 cells analyzed per mouse, one - way ANOVA, Bonferroni post hoc). Scale bar, 10 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "H&E staining of cerebellum, hippocampus, cortex and liver from WT and ASM-KO mice 48 hours after one single administration of vehicle or the indicated doses of PF. Scale bar, 100 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Mean ± SEM SM levels, expressed as percentage of vehicle values, in cerebellar, hippocampal, cortical and liver extracts from WT and ASM-KO mice 48 hours after one single administration of vehicle or the indicated doses of PF. (*PKOVeh Vs KO 5 = 0.0304, n = 3 mice per group, one - way ANOVA, Bonferroni post hoc)",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Immunofluorescences against the microglia marker Iba1 in the cerebellum, hippocampus, cortex or against the macrophage marker F4/80 in the liver from WT and ASM-KO mice 48 hours after one single administration of vehicle or the indicated doses of PF. Graphs show mean ± SEM number of microglia per area unit in cerebellum, hippocampus and cortex or mean ± SEM area of macrophages in the liver (Hippocampus **PKOVeh Vs KO 5 = 0.0015, Cortex *PKOVeh Vs KO 5 = 0.0364, Liver *PKOVeh Vs KO 5 = 0.0152, n = 6 mice per group, > 20 cells analyzed per mouse, one - way ANOVA, Bonferroni post hoc). Scale bar, 10 μm.",
    "ncbi_link": "ASM: 100340"
  },
  {
    "caption": "Western blot against CB1 and GAPDH (used as loading control) and graph showing mean ± SEM CB1 protein levels in cerebellar extracts from WT and Npc1nmf164 mice (n = 6).",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "Immunofluorescence images against CB1 and Calbindin in the cerebellum of WT and Npc1nmf164 mice. DAPI stains cell nuclei. Graphs show mean ± SEM intensity associated to CB1 in the Purkinje cells (indicated by arrows) expressed in arbitrary units (**P= 0.0085, n = 5 mice per group, Student's t-test). Scale bar, 10 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "Graphs show mean ± SEM SM and cholesterol levels expressed as percentage of the values obtained in the vehicle treated mice in the cerebellum of Npc1nmf164 after 48 hours of a single dose of 5mg/kg PF (n=3 mice)",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": "Immunofluorescence images against the microglia marker F4/80 in the cerebellum of WT and Npc1nmf164 after 48 hours of a single dose of 5mg/kg PF. Graphs show mean ± SEM number (upper) and area (lower) of F4/80 positive cells (upper graph ****P< 0.0001; lower graph ***PWT Veh vs NPC Veh = 0.0008; *PWT Veh vs. NPC PF = 0.0286; ****PWT PF vs. NPC Veh < 0.0001; **PWT PF vs. NPC PF = 0.0022, n = 3 mice per group, > 20 cells analyzed per mouse, one - way ANOVA, Bonferroni post hoc). Scale bar, 10 μm.",
    "ncbi_link": "Npc1: 18145"
  },
  {
    "caption": " C-F) Lollipop plots showing the location, abundance, and impact of SNVs in C) TP53, D) PIK3CA, E) PTEN, and F) ERBB2 on the respective encoded protein. Protein change labels are shown for the most mutated amino acid positions, with residues ordered left to right by mutation frequency within each label. ",
    "ncbi_link": "ERBB2: 2064
PIK3CA: 5290
PTEN: 5728
TP53: 7157"
  },
  {
    "caption": " A-E) Overall survival (OS) of patients with tumors containing mutations in the genes A) TP53, B) PIK3CA, C) ERBB2, and D) PTEN. E) OS by PTEN-MutExp genotype (\"low\" defined as PTEN mutation or PTEN expression in the lower quartile across the cohort, \"normal\" otherwise) stratified by groups receiving no systemic treatment (n=336), endocrine therapy only (Endo only; n=1,579), endocrine and chemotherapy (Endo + Chemo ± any; n=914), as well as HER2 treatment with any other treatment or none (HER2 ± any; n=348). Specific treatments in these groups are detailed in Table EV5. In each Kaplan-Meier plot, wildtype (wt) and normal cases are plotted in blue, mutated (mut) and low cases are plotted in red, the log-rank P value is given, and the hazard ratio (HR) for mutation/low is given with a 95% CI and after uni-variable and multi-variable (MV) Cox regression adjustment. Covariables included in the MV analysis were age at diagnosis, lymph node status, tumor size, and the variables denoted by the following symbols: ¶, ER, PgR, HER2, and NHG; ¤, ER, PgR, and NHG; $, HER2 and NHG. Abbreviations: ER, estrogen receptor; PgR, progesterone receptor; HER2, human epidermal growth factor receptor 2; NHG, Nottingham histological grade. ",
    "ncbi_link": "ERBB2: 2064
PIK3CA: 5290
PTEN: 5728
TP53: 7157"
  },
  {
    "caption": "Live cells DIC images and DAPI nucleoids staining of WT DHFR and I91L+W133V DHFR strains after being grown at 30°C, 37°C, or 42°C (I91L+W133V was grown at 40°C) in M9 medium supplemented with amino acids for 4 hours (see Methods).",
    "ncbi_link": "DHFR: 944790"
  },
  {
    "caption": "Functional complementation of WT DHFR from an arabinose inducible pBAD plasmid rescues filamentation of mutant strains grown at 42°C (for WT, W133V and V75H+I155A strains) or at 40°C (for I91L+W133V and V75H+I91L+I155A) in M9 medium supplemented with amino acids. For the boxplots in panels , F the central band represents the median of the distribution, the box ends represent the 25th and 75th percentile, the whiskers represent the 10th and 90th percentile, while the dots represent the 5th and 95th percentile. Data was usually obtained from 2-3 biological replicates. The number of cells used to derive the boxplot distributions in the different panels range usually between 200 to 450 (please refer to Figure 1 source data for exact number of cells for each dataset). See related Figure EV1B.",
    "ncbi_link": "DHFR: 944790"
  },
  {
    "caption": "(A) recA (B) recN genes measured by quantitative PCR when WT and mutant strains are grown in M9 medium with or without supplementation of amino acids or dTMP. WT and mutant strains were grown for 4 hours of growth in the indicated medium at 37°C, while WT treated with different concentrations of Tmp were grown for 4 hours at 42°C. Brown bars (M9+AA) in the gray shaded area correspond to filamentation conditions and these are associated with pronounced upregulation of all three SOS genes. On the other hand, conditions with loss of filamentation (with dTMP or no supplementation) show much less expression. Error bars represent SD of 2-3 biological replicates (see Methods).",
    "ncbi_link": "recA: 947170
recN: 947105"
  },
  {
    "caption": "Expression of SOS response genes recA, recN and sulA when mutant strains and Tmp treated WT cells are grown in M9 medium supplemented with amino acids (black bars) or in the presence of both amino acids and GMP (gray bars) at 42°C (I91L+W133V was grown at 40°C). Error bars represent SD of 2-3 biological replicates.",
    "ncbi_link": "recA: 947170
recN: 947105
sulA: 947335"
  },
  {
    "caption": "Comparison of growth rates of WT and mutant DHFR strains at 42°C (40°C for I91L+W133V and V75H+I91L+I155A) in minimal medium that is supplemented with amino acids and/or 1mM dTMP. Except for W133V and to a lesser extent for V75H+I155A, the effect of dTMP on growth rates is only modest. Error bars represent SEM of 3 biological replicates.",
    "ncbi_link": "DHFR: 944790"
  },
  {
    "caption": "Steady state levels of different metabolites obtained from metabolomics were used to derive activity curves for (A) Adenylate Kinase (AK) (B) Uridylate Kinase (PyrH) (C) Adenylosuccinate Lyase (PurB) and (D) GAR Transformylase (PurN). AK, PyrH and PurB appear to follow hyperbolic MM kinetics in vivo, while PurN shows Hill-like dependence with cooperativity. In panel (A), the red data points were acquired during growth in amino acid supplemented M9 medium in the absence of external AMP and are derived from WT and various stabilizing and destabilizing point mutations of AK (Adkar et al., 2019) as well as DHFR mutants used in the present study, while black points were derived exclusively from cultures of AK mutants supplemented with 1mM external AMP (Adkar et al., 2019). Data points for all other panels (B-D) are derived from mutant DHFR strains in the present study. Since SAICAR, AICAR, GAR and FGAR levels were undetectable in WT, all data points in (C-D) are relative to those observed in I91L+W133V mutant following 4 hours of growth at 40°C. Data points in all panels represent metabolite levels for individual biological replicates without averaging.",
    "ncbi_link": "AK: 945097
DHFR: 944790"
  },
  {
    "caption": "B Levels of INPP5Eprotein 72 h after transfection of N1E-115 cells with control (siControl) or INPP5E-specific siRNAs (siINPP5E #1 or #2), as determined by immunoblot.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "C N1E-115 cells treated with siControl or siINPP5Es were cultured for 2 h in growth medium with or without 125 nM bafilomycin A1 (Baf.A1), and then analyzed by immunoblot using anti-p62, anti-LC3, and anti-GAPDH antibodies.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "E N1E-115 cells treated with siControl or siINPP5Es were cultured in growth medium. Cells were fixed and stained with anti-LC3 antibodies and analyzed by immunofluorescencemicroscopy. Bar, 10 µm.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "A N1E-115 cells treated with siControl, siINPP5E, or siAtg2a/2b were cultured in growth medium. The post-nuclear fraction (PNS) was separated into LSP, HSP, and HSS fractions, and then analyzed by immunoblots using anti-p62, anti-LC3, and GAPDH antibodies. The subfractions were treated with proteinase K (Pro. K) with or without Triton X-100. Quantitation of protein signal intensities from immunoblots showing LC3-II (left) or p62 (right) levels, following normalization to the control protein GAPDH. **, P < 0.01; *, P < 0.05.",
    "ncbi_link": "Atg2a: 329015
INPP5E: 64436"
  },
  {
    "caption": "B NIE-115 cells stably expressing LAMP1-mCherry treated with siControl or siINPP5Es were cultured for 2 h in growth medium containing 200 nM Torin1 with protease inhibitors (10 µg/ml Pepstatin A and 10 µg/ml E-64-d). Because the treatment of protease inhibitors inhibits lysosomal degradation, LC3puncta persist even ifautophagosomes fuse with lysosomes. Cells were fixed and stained with anti-LC3 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm.C Percentages of colocalization of LC3 dots with LAMP1 dots (mean ± s.d.; n > 20 cells from three independent experiments). **, P < 0.01.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "B N1E-115 cells stably expressing mSt-INPP5E (WT, D477N, ∆CAAX, or 295-644) treated with siControl or siINPP5E were cultured in growth medium with or without 125 nM Baf.A1 for 2 h, and then analyzed by immunoblot using anti-LC3 and anti-GAPDH antibodies. The mSt-INPP5Es used in this study were resistant to mouse siINPP5E because target sequence of the siRNA is different from the human correspondent sequence.C Quantitation of protein signal intensities from immunoblots in B, showing differences in LC3-II levels in the presence and absence of Baf.A1 following normalization to the control proteinGAPDH. Results represent means ± s.d. of three independent experiments. **, P < 0.01; *, P < 0.05.",
    "ncbi_link": "INPP5E: 64436
INPP5E: 56623"
  },
  {
    "caption": "D NIE-115 cells stably expressing mSt-INPP5E (WT, D477N, or ΔCAAX) were cultured in growth medium. Cells were fixed and stained with anti-LAMP1 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. The number showing to the right side indicates the colocalization rate of LAMP1 with mSt-INPP5E. Bar, 10 µm.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "A N1E-115 cells treated with siControl or siINPP5Es were cultured in growth medium with 20 µg/ml DQ-BSA for 12 h and chased for 2 h. Cells were fixed and stained with anti-LAMP1 antibodies and analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm.B Quantitation of signal intensities in A showing colocalization of DQ-BSA with LAMP1 (means ± s.d.; n > 50 cells from three independent experiments). Baf.A1 was used as a control for inhibition of delivery and degradation of DQ-BSA via the endocytic pathway. **, P < 0.01; n.s., non significant.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "C N1E-115 cells treated with siControl, siINPP5Es, or siCHMP5 were stimulated with 100 ng/ml EGF for the indicated time periods, and then analyzed by immunoblot using anti-EGFR and anti-α-tubulin antibodies. Levels of CHMP5 mRNA72 h after transfection of N1E-115 cells with siControl or siCHMP5, as analyzed by RT-PCR.D Quantitation of EGFR degradation ratio in C. Results represent means ± s.d. of three independent experiments. **, P < 0.01.",
    "ncbi_link": "CHMP5: 76959
INPP5E: 64436"
  },
  {
    "caption": "A NIE-115 cells stably expressing mSt-2xML1N or -2xPLCδ1PH were cultured in growth medium with or without 200 nM Torin1. Cells were fixed and stained with anti-LAMP1 or anti-LC3 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm.",
    "ncbi_link": "ML1N: 
PLCδ1: "
  },
  {
    "caption": "B NIE-115 cells stably expressing mSt-2xML1N treated with siControl or siINPP5Es were cultured in growth medium. Cells were fixed and stained with anti-LAMP1 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm.",
    "ncbi_link": "ML1N: 
INPP5E: 64436"
  },
  {
    "caption": "D N1E-115 cells stably expressing GFP-2xML1N treated with siControl or siINPP5E were transiently transfected with mSt-INPP5E (WT, D477N). Quantitation of signal intensities showing GFP-2xML1N colocalizing with LAMP1 (means ± s.d.; n > 20 cells from three independent experiments). **, P < 0.01; *, P < 0.05.",
    "ncbi_link": "ML1N: 
INPP5E: 64436"
  },
  {
    "caption": "E NIE-115 cells stably expressing mCherry-2xFYVE treated with siControl or siINPP5Es were cultured in growth medium. Cells were fixed and stained with anti-LAMP1 antibodies, and then analyzed by immunofluorescence microscopy. Insets show the boxed areas at high magnification. Bar, 10 µm.F Quantitation of signal intensities in E showing mCherry-2xFYVE colocalizing with LAMP1 (means ± s.d.; n > 100 cells from three independent experiments). **, P < 0.01.",
    "ncbi_link": "FYVE: 
INPP5E: 64436"
  },
  {
    "caption": "A N1E-115 cells treated with siControl or siINPP5Es were cultured in growth medium. Cells were fixed and stained with anti-LAMP1 antibodies and Phalloidin, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm. Quantitation of signal intensities showing Phalloidin colocalizing with LAMP1 (means ± s.d.; n > 40 cells from three independent experiments). **, P < 0.01.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "B N1E-115 cells treated with siControl or siINPP5Es were cultured in growth medium. Cells were fixed and stained with anti-phospho-Y421 cortactin and anti-LAMP1 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm. Quantitation of signal intensities showing cortactin (pY421) colocalizing with LAMP1 (means ± s.d.; n > 40 cells from three independent experiments). **, P < 0.01.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "D NIE-115 cells stably expressing LAMP1-mCherry were treated with DMSO or 0.5 µM Lat A in growth medium for 4 h, subsequently cultured with 200 nM Torin1 and protease inhibitors (10 µg/ml Pepstatin A and 10 µg/ml E-64-d) for 2 h (Lat A treatment for total 6h). Cells were fixed and stained with anti-LC3 antibodies, and then analyzed by immunofluorescencemicroscopy. Insets show the boxed areas at high magnification. Bar, 10 µm. Percentages of colocalization of LC3 dots with LAMP1 dots (mean ± s.d.; n > 20 cells from three independent experiments). **, P < 0.01.",
    "ncbi_link": "LAMP1: 16783"
  },
  {
    "caption": "B N1E-115 cells stably expressing the indicated mutants treated with siControl or siINPP5E were cultured in growth medium with or without 125 nM Baf.A1 for 2 h, and analyzed by immunoblot using anti-LC3 and anti-GAPDH antibodies. The mutants were resistant to mouse siINPP5E because target sequence of the siRNA is different from the human correspondent sequence.C Quantitation of protein signal intensities from immunoblots in B showing differences in LC3-II levels in the presence and absence of Baf.A1 following normalization to the control proteinGAPDH. Results represent means ± s.d. of three independent experiments. **, P < 0.01; *, P < 0.05.",
    "ncbi_link": "INPP5E: 64436"
  },
  {
    "caption": "(H). Budding yeast cells expressing fusions of Spt5N and Spt5N-3A to Protein A were grown in parallel with cells expressing the equivalent wild type and mutant versions of fission yeast Spt5N (Sp Spt5N and Sp Spt5N-3A - the latter contained the F146A, E150A and V153A mutations).",
    "ncbi_link": "Spt5: 854999
Spt5: 2541916"
  },
  {
    "caption": "(C) Yeast cells were generated that expressed Protein A-tagged versions of wild type Spt5 (full length or the indicated truncations), or full length Spt5-3A, under the control of the GAL1,10 promoter. Cells were grown in medium containing galactose and the ProteinA-tagged Spt5 proteins were isolated from cell extracts on magnetic beads coated with IgG. Association of the tagged Spt5 proteins with the elongating form of Pol II was monitored by immunoblotting, using antibodies specific to the indicated phosphorylation sites in the C-Terminal Domain repeats of the Rpb1 subunit of Pol II.",
    "ncbi_link": "Protein A: 
GAL1: 852308
Spt5: 854999"
  },
  {
    "caption": "(E) Serial dilutions of control cells or spt5-AID cells, expressing the indicated versions of Spt5 from the GAL1,10 promoter, were grown on the indicated medium.",
    "ncbi_link": "GAL1: 852308
spt5: 854999
Spt5: 854999"
  },
  {
    "caption": "A, B MARS (A) and MARS2 (B) mRNA expression levels were measured by real-time PCR in blood samples with 2 and 3-4 copies. Relative expression levels were normalized to GAPDH levels, and data were quantified relative to the mRNA expression levels of 2 copy samples. Data are presented as the mean ± SEM. *P ≤ 0.05, **P ≤ 0.01. Unpaired Student's t test",
    "ncbi_link": "GAPDH: 2597
MARS: 4141
MARS2: 92935"
  },
  {
    "caption": "L MARS2 mRNA expression in embryonic chorion (C) and maternal deciduae (D) were detected by qPCR (n=6). Data are presented as the mean ± SEM. *P ≤ 0.05, **P ≤ 0.01. Wilcoxon matched pairs test was used",
    "ncbi_link": "MARS2: 92935"
  },
  {
    "caption": "N MARS mRNA levels (n=6) in the brains of foetal rats (F) and their corresponding mothers (M) were determined by qPCR (n=6). Data are presented as the mean ± SEM. *P ≤ 0.05, **P ≤ 0.01. Wilcoxon matched pairs test was used",
    "ncbi_link": "MARS: 299851"
  },
  {
    "caption": "B Cell growth was determined in the absence and presence of 0.5 mM homocysteine or 0.5 mM methionine in the culture media of NE4C cells transfected with pcDNA3.1 vector or pcDNA3.1-Flag-Bcl-2 plasmids (n=3). 5μg plasmids were transfected in each 1×106 cells. The cell index responds to changes in cell number and cell adhesion. Cleaved caspase 3 (c-caspase3) levels were detected to determine apoptosis levels (right). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test.",
    "ncbi_link": "Flag: 
Bcl-2: 12043"
  },
  {
    "caption": "C, D Apoptotic cells were detected by flow cytometry. The apoptotic rates of untreated, MARS (C)-, and MARS2 (D)-over-expressing NE4C cells when cultured in the absence and presence of 20 μM homocysteine were normalized to the untreated NE4C cells (n=4). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, ***P ≤ 0.001.",
    "ncbi_link": "MARS: 4141
MARS2: 212679"
  },
  {
    "caption": "F Apoptotic rates were determined in the absence and presence of 20 μM homocysteine in the culture media of control and MARS/MARS2 knockdown NE4C cells (n=4). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, ***P ≤ 0.001.",
    "ncbi_link": "MARS: 216443
MARS2: 212679"
  },
  {
    "caption": "HTL and ROS (superoxide) levels were compared (n=4) between NE4C cells transfected with the empty vector, MARS (A) plasmids. Data were normalized against that of vector-transfected cells. HTL levels were determined by LC-MS, and ROS levels were determined by DHE staining assay.",
    "ncbi_link": "MARS: 4141"
  },
  {
    "caption": "HTL and ROS (superoxide) levels were compared (n=4) between NE4C cells transfected with the empty vector or MARS2 (B) plasmids. Data were normalized against that of vector-transfected cells. HTL levels were determined by LC-MS, and ROS levels were determined by DHE staining assay.",
    "ncbi_link": "MARS2: 212679"
  },
  {
    "caption": "C MARS was knocked down by small hairpin RNAs in NE4C cells. MARS knockdown efficiencies were confirmed by western blot. HTL and superoxide levels were quantified (n=4) relative to vector-transfected NE4C cells. Cells were cultured in 20 μM Hcy-containing media.",
    "ncbi_link": "MARS: 216443"
  },
  {
    "caption": "D Relative superoxide levels were determined by DHE staining assay and compared (n=4) between NE4C cells with and without MARS knockdown by shRNA. Cells were cultured in 20 μM Hcy-containing media. MARS2 knockdown efficiencies were confirmed by western blot.",
    "ncbi_link": "MARS: 212679
MARS2: 212679"
  },
  {
    "caption": "E NE4C cells with and without MARS knockdown were treated with either Hcy (20 μM) or Met (75 μM), and cellular superoxide levels were detected 6 h after the start of the respective treatment and quantified relative to the untreated NE4C cells (n=4).",
    "ncbi_link": "MARS: 216443"
  },
  {
    "caption": "G Superoxide levels in response to Hcy treatment (20 μM, 4 h) in MARS-expressing and control cells were determined relative to the untreated NE4C cells.",
    "ncbi_link": "MARS: 4141"
  },
  {
    "caption": "I Protein N-Hcy levels in response to MARS knockdown (by shRNA) and over-expression were detected by western blot.",
    "ncbi_link": "MARS: 4141"
  },
  {
    "caption": "J, K Untreated and MARS/MARS2 knockdown NE4C cells were treated with Hcy (20 μM) or HTL (10 μM), and the N-Hcy (J) levels (n=4) in cells were detected 6 h after the start of the respective treatment and quantified relative to untreated NE4C cells. Error bars indicate SEM. Data were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "MARS: 216443
MARS2: 212679"
  },
  {
    "caption": "J, K Untreated and MARS/MARS2 knockdown NE4C cells were treated with Hcy (20 μM) or HTL (10 μM), and superoxide (K) levels (n=4) in cells were detected 6 h after the start of the respective treatment and quantified relative to untreated NE4C cells. Error bars indicate SEM. Data were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "MARS: 216443
MARS2: 212679"
  },
  {
    "caption": "D Upon switching N-Hcy substrate lysine (K) sites to nonmodifiable tryptophan (W), the N-Hcy unmodifiable mutants displayed lower specific activity than the wide-type (WT) SOD. SOD1 (WT, K23W, K122W, K128W, and 3KW) and SOD2 (WT, K44W, K51W, K98W, K106W, K178W, and 5KW) were expressed in HEK293T cells. The catalytic activity of affinity-purified SOD proteins was determined and normalized to protein levels. Wild-type SOD1 and SOD2 activities were set at 100% (n=4). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "SOD1: 6647
SOD2: 6648"
  },
  {
    "caption": "E, F Hcy and HTL treatment in NE4C cells increased N-homocysteinylation of SODs and decreased their activities. Flag-tagged SOD1 and SOD2 were each ectopically expressed in NE4C cells. The cells were transferred to serum-free DMEM with or without 20 μM Hcy (E) or 10 μM HTL (F) 6 h before harvesting. After affinity purification, the specific activities of SOD1 and SOD2 were determined and normalized to SOD1 and SOD2 activity in untreated cells. Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
SOD1: 6647
SOD2: 6648"
  },
  {
    "caption": "G N-Hcy SOD levels were down-regulated in MARS/MARS2 knockdown cells. Flag-tagged SOD1 and SOD2 were each over-expressed in untreated and MARS/MARS2 knockdown NE4C cells. After affinity purification, the N-Hcy levels and relative specific activities of purified SOD1 and SOD2 were determined and quantified relative to the NE4C cells (n=4). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
MARS: 216443
MARS2: 212679
SOD1: 6647
SOD2: 6648"
  },
  {
    "caption": "D Levels of β-catenin in untreated and MARS knockdown NE4C cells were detected (n=3) with the presence or absence of 20 μM Hcy in the culture media. Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "MARS: 216443"
  },
  {
    "caption": "NE4C cells were co-transfected with NRX-Flag and DVL1-Myc plasmids and treated with different concentrations of Hcy (E) The relative amount of DVL1 that coimmunoprecipitated (co-IPed) with NRX-Flag was determined (n=3). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
Myc: 
DVL1: 13542
NRX: 18230"
  },
  {
    "caption": "NE4C cells were co-transfected with NRX-Flag and DVL1-Myc plasmids and treated with different concentrations of HTL (F). The relative amount of DVL1 that coimmunoprecipitated (co-IPed) with NRX-Flag was determined (n=3). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
Myc: 
DVL1: 13542
NRX: 18230"
  },
  {
    "caption": "G NRX-Flag and DVL1-Myc were co-transfected in untreated or MARS knockdown NE4C cells. The relative DVL1 levels that co-IPed with NRX-Flag were determined and quantified (n=3) for treated and control cells cultured with or without 20 μM Hcy. Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
Myc: 
DVL1: 13542
MARS: 216443
NRX: 18230"
  },
  {
    "caption": "Flag-tagged SOD1 and SOD2 were co-over-expressed in NE4C cells cultured in DMEM and supplemented with Hcy or HTL. (H) The levels of β-catenin in cells with and without SOD1/2 expression were determined (n=3). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons.",
    "ncbi_link": "Flag: 
SOD1: 
SOD2: "
  },
  {
    "caption": "Flag-tagged SOD1 and SOD2 were co-over-expressed in NE4C cells cultured in DMEM and supplemented with HTL. (I) Relative levels of DVL1 that co-IPed with NRX-Flag were quantified in SOD-expressing and control cells cultured with or without 10 μM HTL (n=3). Data are presented as the mean ± SEM and were compared using an unpaired Student's t test. nsnot significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. One-way ANOVA with Dunnett's correction was used for multiple comparisons. ",
    "ncbi_link": "Flag: 
SOD1: 6647
SOD2: 6648
SOD: 6648///6647"
  },
  {
    "caption": "(A-B) Primary cilia are enriched at branch points and the greater curvature of the aorta of wild type mice, schematized in (A) and quantified in (B). The color in (A) indicates which side of the aorta is quantified in (B). Numbers indicate the region of the aorta (A) whose proportion of ciliated cells is quantified in (B). Error bars are +/- 1 S.E.M and n=7 mice. (C) Aortic endothelial cilia are ablated in Tek-Cre Ift88C/- mice. Endothelial cells and cilia are labeled by staining for Pecam1 and Arl13b, respectively. Scale bars are 10μm.",
    "ncbi_link": "Cre: 
Ift88: 21821
Tek: 21687"
  },
  {
    "caption": "(B) Loss of EC cilia by Tek-Cre increases atherosclerosis in the aortas of Apoe-/- mice on a high-fat high-cholesterol diet as visualized by Oil Red O (ORO) staining (left panels) whereas loss of cilia genes in blood by Mx1-Cre has no effect (right panels).(C) Cropped views of the boxed areas in (B) showing increased atherosclerosis in mice with Tek-Cre but not Mx1-Cre mediated loss of Ift88 in the aortic arch.(D-G) Scatter plots of the percent ORO-positive area of the thoracic aorta in (D-E) Tek-Cre and (F-G) Mx1-Cre mice, separated by (D, F) females and (E, G) males. Tek-Cre Apoe-/- Ift88C/- mice had a 58.9% (p=0.0135, Student's 2-tailed t-test, n=13 control and n=10 mutant mice) and 67% (p=0.0106, Student's 2-tailed t-test, n=17 control and n=14 mutant) increase in ORO-positive area versus control littermates in females and males, respectively. Mx1-Cre Apoe-/- Ift88C/- mice had no significant difference in ORO-positive area in females (p=0.6643, Student's 2-tailed t-test, n=7 control and mutant mice) or males (p=0.9381, Student's 2-tailed t-test, n=9 control and n=7 mutant mice). Black bars represent the mean and error bars are +/- 1 S.E.M. Aortas depicted in (B-C) are red in the scatter plots.",
    "ncbi_link": "Cre: 
Apoe: 11816
Ift88: 21821
Mx1: 17857
Tek: 21687"
  },
  {
    "caption": "(A) Transcripts for the inflammatory cytokines Il1b, Il6, Tnf1 and Tgfb1, the adhesion molecules Vcam1 and Sele, the lymphocyte marker Nos2 and macrophage marker Cd68, and the NFκB responsive genes Tnfaip3 and Hmox1 were upregulated in aortas from Apoe-/- mice lacking EC cilia by RT-qPCR, while transcripts of the Hh target genes Gli1, Ptc1, and Ptc2 were not. Error bars are +1 S.E.M. n=8 control and n=10 mutant mice of mixed sex. P-values calculated by Student's 2-tailed t-test.",
    "ncbi_link": "Apoe: 11816
Cd68: 12514
Gli1: 14632
Hmox1: 15368
Il1b: 16176
Il6: 16193
Nos2: 18126
Ptc1: 19206
Ptc2: 19207
Sele: 20339
Tgfb1: 21803
Tnf1: 21926
Tnfaip3: 21929
Vcam1: 22329"
  },
  {
    "caption": "Immunoblot  analysis of phosphorylated ERK1/2 (P-ERK1/2), phosphorylated p38  (P-P38), phosphorylated JNK1/2 (P-JNK1/2), phosphorylated p65  subunit of NF-κB (P-P65), total P65, MEKK2, TRAF2, TRAF3, TRAF6, NEDD4L, and actin  in HeLa  cells transfected with Nedd4l siRNA (siNedd4l) or control RNA (siNC) (A) , treated with  IL-17 for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. Densitometry  of MEKK2  was relative to actin. All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 23327"
  },
  {
    "caption": "Immunoblot  analysis of phosphorylated ERK1/2 (P-ERK1/2), phosphorylated p38  (P-P38), phosphorylated JNK1/2 (P-JNK1/2), phosphorylated p65  subunit of NF-κB (P-P65), total P65, MEKK2, TRAF2, TRAF3, TRAF6, NEDD4L, and actin  in Nedd4l+/+ and Nedd4l-/- MEFs  , treated with  IL-17 for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated proteins relative to that of total proteins, respectively. Densitometry  of MEKK2 was relative to actin. All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "Immunoblot  analysis of phosphorylated p38  (P-P38), phosphorylated p65  subunit of NF-κB (P-P65), total P65, MEKK2, NEDD4L, and actin  in Nedd4l+/+ and Nedd4l-/- primary  lung epithelial cells (C), or Nedd4l+/+ and Nedd4l+/- astrocytes (D) , treated with   IL-17  for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. Densitometry  of MEKK2  was relative to actin. All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "(E) Immunoblot  analysis of phosphorylated p65  subunit of NF-κB (P-P65), total P65, phosphorylated p38  (P-P38), total P38, MEKK2, NEDD4L, and actin  in HeLa  cells transfected with Myc-tagged NEDD4L，Myc- tagged NEDD4L-CA(C942A), or Myc- tagged Null plasmids, treated with   IL-17  for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. Densitometry  of MEKK2  was relative to actin. All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Myc: 
NEDD4L: 83814"
  },
  {
    "caption": "(F)Immunoblot  analysis of MEKK2, TRAF2, TRAF6, NEDD4L, and actin  in Nedd4l+/+, Nedd4l+/-, and Nedd4l-/- MEFs. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. Densitometry  of MEKK2  was relative to actin. All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "(G)Immunoblot  analysis of MEKK2  in lysates of Nedd4l+/+ and Nedd4l-/- MEFs  treated with CHX  (50 μg/ ml) for indicated time. (H)The intensity values were measured by Image J software to calculate half-life of MEKK  protein ( n = 3 biological replicates). Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. Densitometry  of MEKK2  was relative to actin. All experiments were performed three times, and representative data are shown. Significant differences were tested using a two-tailed Student's t-test. *P<0.05, **P<0.01. NS, no significance.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "(C)Immunoblot  of HA-tagged MEKK2 co-immunoprecipitated with anti-Myc  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing HA-tagged MEKK2  and Myc-tagged wild-type NEDD4L  or mutant NEDD4L  with C2 (∆C2), WW (∆WW) or HECT (∆HECT) domain deleted. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "HA: 
Myc: 
MEKK2: 10746
NEDD4L: 83814"
  },
  {
    "caption": "(D)Immunoblot  analysis of MEKK2  and NEDD4L  in Nedd4l+/+, and Neddl4- /- treated with DMSO, 20μM MG-132, or 0.2 μM bafilomycin A1 (Baf A1) for 6 h. Densitometry  of MEKK2  was relative to actin. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 83814
Neddl4: 83814"
  },
  {
    "caption": "(F)Immunoblot  analysis of K48-, K63-linked, and total ubiquitination  of MEKK2  following precipitation of MEKK2  with MEKK2-specific antibody from lysates of Nedd4l+/+ and Nedd4l-/- MEFs  treated with  MG-132. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Nedd4l: 83814"
  },
  {
    "caption": "(G)Immunoblot  analysis of total ubiquitination  of Flag-tagged MEKK2 following precipitation of MEKK2  with Flag-tagged specific antibody from lysates of HEK293T  cells co-transfected with plasmids expressing Flag-tagged MEKK2  and Myc-tagged wild-type NEDD4L  or mutant NEDD4L  with C2 (∆C2), WW (∆WW) or HECT (∆HECT) domain deleted. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Flag: 
Myc: 
MEKK2: 10746
NEDD4L: 83814"
  },
  {
    "caption": "(H)Immunoblot  analysis of total ubiquitination  of Flag-tagged MEKK2  following immunoprecipitating MEKK2  with anti-Flag  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing Flag-tagged MEKK2, Myc-tagged NEDD4L, and HA-tagged wild-type or K6O, K11O, K27O, K29O, K33O, K48O, K63O mutant Ub. (I)Immunoblot  analysis of total ubiquitination  of Flag-tagged MEKK2  following immunoprecipitating MEKK2  with anti-Flag  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing Flag-tagged MEKK2, Myc-tagged NEDD4L, and HA-tagged wild-type or K6R, K11R, K27R, K29R, K33R, K48R, K63R mutant Ub. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
MEKK2: 10746
NEDD4L: 83814
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "(J)Immunoblot  analysis of total ubiquitination  of Flag-tagged MEKK2  following immunoprecipitating MEKK2  with anti-Flag  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing Flag-tagged MEKK2, increased dosage of Myc-tagged NEDD4L, and HA-tagged wild-type, K27O, or K63O mutant Ub. Data information: All experiments were performed three times, and representative data are shown.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
MEKK2: 10746
NEDD4L: 83814
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "(A, Immunoblot  analysis of phosphorylated p38  (p-p38), phosphorylated NF-κB p65  (P-P65), MEKK2  and actin  in HeLa  cells (A) transfected with Mekk2  siRNA (siMekk2) or control RNA (siNC) and stimulated with IL-17 (HeLa  cells 50 ng/ml, for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Mekk2: 10746"
  },
  {
    "caption": "B) Immunoblot  analysis of phosphorylated p38  (p-p38), phosphorylated NF-κB p65  (P-P65), MEKK2  and actin  in MEFs (B) transfected with Mekk2  siRNA (siMekk2) or control RNA (siNC) and stimulated with  IL-17 MEFs  100ng/ml) for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Mekk2: 26405"
  },
  {
    "caption": "(C,  Realtime PCR analysis of  Il-6, Cxcl2, and Ccl20  mRNA expression in HeLa  cells (C) transfected with siRNA (siMekk2) or control RNA (siNC) and stimulated with   IL-17 (HeLa  cells 50 ng/ml, for indicated time  (n = 3 technical replicates). Data information: Data are shown as the mean ± s.e.m. of technical replicates. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Ccl20: 6364
Cxcl2: 2920
Il-6: 3569
Mekk2: 10746"
  },
  {
    "caption": "D)  Realtime PCR analysis of  Il-6, Cxcl2, and Ccl20  mRNA expression in MEFs (D) transfected with siRNA (siMekk2) or control RNA (siNC) and stimulated with IL-17 MEFs  100ng/ml) for indicated time  (n = 3 technical replicates). Data information: Data are shown as the mean ± s.e.m. of technical replicates. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Ccl20: 20297
Cxcl2: 20310
Il-6: 16193
Mekk2: 26405"
  },
  {
    "caption": "(E) Immunoblot  analysis of phosphorylated p38, phosphorylated NF-κB p65  (P-P65), NEDD4L, MEKK2  and actin  in HeLa  cells transfected with control RNA (siNC), Nedd4l  siRNA (siNedd4l), Mekk2  siRNA(siMekk2) or Nedd4l  siRNA plus Mekk2  siRNA (siNedd4l+ siMekk2), and stimulated with   IL-17(50 ng/ml) for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Mekk2: 10746
Nedd4l: 23327"
  },
  {
    "caption": "(F) Immunoblot  analysis of phosphorylated p38, phosphorylated NF-κB p65  (p-p65), NEDD4L, MEKK2  and actin  in Nedd4l+/+ and Nedd4l-/-MEFs  transfected with Mekk2  siRNA (siMekk2) or control RNA (siNc), and stimulated with   IL-17 (100 ng/ml) for indicated time. Data information: Numbers between two blots  indicate densitometry  of phosphorylated  proteins relative to that of total proteins, respectively. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Mekk2: 26405
Nedd4l: 83814"
  },
  {
    "caption": "(G, Realtime PCR  analysis of  Il-6, Cxcl2, and Ccl20  mRNA expression in HeLa  cells (G) treated as described in (E) (n = 3 technical replicates). Data information: Data are shown as the mean ± s.e.m. of technical replicates. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Ccl20: 6364
Cxcl2: 2920
Il-6: 3569"
  },
  {
    "caption": "H) Realtime PCR analysis of  Il-6, Cxcl2, and Ccl20  mRNA expression in MEFs (H) treated as described in (F) (n = 3 technical replicates). Data information: Data are shown as the mean ± s.e.m. of technical replicates. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Ccl20: 20297
Cxcl2: 20310
Il-6: 16193"
  },
  {
    "caption": "(B) Realtime PCR  analysis of Il-6, Cxcl2, and Ccl20  mRNA expression in HeLa  cells transfected with HA-tagged MEKK2  S520A or control vector, and stimulated with IL-17 (50 ng/ml) for indicated time  (n = 3 technical replicates). Data information: Data are shown as the mean ± s.e.m. of technical replicates. All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "HA: 
Ccl20: 6364
Cxcl2: 2920
Il-6: 3569
MEKK2: 10746"
  },
  {
    "caption": "(E)Immunoblot  analysis of Ser520 phosphorylation of MEKK2 immunoprecipitated  from HeLa  cells transfected with Tak1-specific (siTak1) or control RNA (siNC), and then stimulated with  IL-17 (50 ng/ml) for indicated time. Data information: All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Tak1: 7182"
  },
  {
    "caption": "(F)Immunoblot  analysis of Myc-tagged NEDD4L co-immunoprecipitated with anti-HA  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing Myc-tagged NEDD4L and HA-tagged wild-type MEKK2 or mutant MEKK2  (S520A). Data information: All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "HA: 
Myc: 
MEKK2: 10746
NEDD4L: 83814"
  },
  {
    "caption": "(G)Immunoblot  analysis of total ubiquitination  of HA-tagged MEKK2  and HA-tagged MEKK2(S520A) following precipitation of MEKK2  with anti-HA  antibody from lysates of HEK293T  cells co-transfected with plasmids expressing HA-tagged MEKK2  or HA-tagged MEKK2(S520A) together with Myc-tagged NEDD4L  and Flag-tagged Ub. Data information: All experiments were performed two times, and representative data are shown.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
MEKK2: 10746
NEDD4L: 83814
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "A and B) Confocal microscopy images showing mitochondrial fragmentation in HBV- and HBx-expressing cells, respectively. Huh7 cells were transiently transfected with HBV (A) or the HBx-flag construct (B). At 2 days post-transfection, cells prestained with MitoTracker (Mito, white) were immunostained with anti-HBsAg (A, green) and anti-flag (B, green) antibodies, respectively. In the zoomed images, typical tubular mitochondria in untransfected cells and fragmented mitochondria in transfected cells are shown.",
    "ncbi_link": "HBx: 944566"
  },
  {
    "caption": "(D-F) Confocal immunofluorescence showing mitochondrial translocation of Drp1 in HBV- and HBx-expressing cells, respectively. Huh7 cells transfected with HBV (D and E) or HBx-flag construct (F) were immunostained with antibodies specific to TOM20 (red), Drp1 (D, green), and phospho-Drp1 (Ser616) (E and F, green), respectively. HBV and HBx gene expression (white) was verified using anti-HBsAg (D and E) and anti-flag (F) antibodies, respectively. In the zoomed images, the yellow color indicates the merge of Drp1 or phospho-Drp1 (Ser616) with mitochondria. (A, B, D, E, and F) Transfected (+) and untransfected (−) cells are marked. Nuclei were stained with DAPI (blue).",
    "ncbi_link": "HBx: 944566"
  },
  {
    "caption": "(D) Mfn2 protein in whole cell lysates extracted from HepAD38 cells transfected with non-targeting (NT) and Parkin (P) siRNA, respectively, for 48 h was immunoprecipitated by anti-Mfn2 antibody, followed by immunoblotting (IB) with anti-ubiquitin (Ub) antibody. Normal mouse IgG was used as a control for immunoprecipitation (IP). The protein expression was analyzed by Western blotting with antibodies specific to Mfn2, Parkin, and β-actin proteins. (",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(E) Intracellular mRNA levels of Parkin, PINK1, and LC3B were analyzed by real-time qRT-PCR. GAPDH was used to normalize changes in Parkin, PINK1, and LC3B gene expression.",
    "ncbi_link": "GAPDH: 2597
LC3B: 81631
Parkin: 5071
PINK1: 65018"
  },
  {
    "caption": "(B) Huh7 cells transiently expressing Mito-mRFP-EGFP were transfected with HBV, HBx-flag, and HBV-ΔX constructs, respectively, for 48 h. Cells were immunostained with antibodies specific to HBsAg and flag (white), respectively. Nuclei were stained with DAPI (blue). Transfected (+) and untransfected (−) cells are marked. In the zoomed images, fluorescence signals indicate the expression of Mito-mRFP-EGFP targeting mitochondria: yellow color, no mitophagy; red color, mitophagy.",
    "ncbi_link": "HBx: 944566"
  },
  {
    "caption": "(A-C) Parkin silencing accelerates HBV-induced mitochondrial apoptotic signaling. HepG2 and HepAD38 cells grown in the absence or presence of tetracycline were transfected with non-targeting (NT) and Parkin siRNA, respectively, for 72 h. Cells were used for Western blot analysis using antibodies specific to the indicated proteins (A), caspase-3/7 activity assay (B), and TUNEL assay (C)",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(B) The DDL transcripts and growth phenotype of ddl-6 and ddl-7. DDL transcripts were detected in fully expanded leaves of four-week-old plants by qRT-PCR (left panel). The expression of DDL in WT Col-0 was set as 1. Plants grown under 12-hr light/12-hr dark condition for 4 weeks are shown (right panel). Bar=1cm.",
    "ncbi_link": "DDL: 821601
ddl: 821601"
  },
  {
    "caption": "(C) ddl-6 and ddl-7 are more susceptible to Pst DC3000 infections. Leaves of four-week-old plants were inoculated with Pst DC3000 at OD600=5x10-4. Bacterial numbers were counted at 0 and 3 dpi. Leaf pictures were taken at 3 dpi.",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(D) The ddl-1 mutant in the Ws background is more susceptible to Pst DC3000 infection.",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(E) ddl-6 is more susceptible to Psminfection. Leaves of four-week-old plants were inoculated with Psmat OD600=5x10-4.",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(F) Increased bacterial growth of Pst DC3000 hrcC in ddl-6. Leaves of four-week-old plants were inoculated with Pst DC3000 hrcC at OD600=5x10-4.",
    "ncbi_link": "ddl: 821601
hrcC: 1183025"
  },
  {
    "caption": "(G) Increased bacterial growth of Psp in ddl-6. Leaves of four-week-old plants were inoculated with Psp at OD600=5x10-4.",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(H) Complementation of DDL in disease resistance. Two independent T3 homozygous lines carrying pDDL::DDL-FLAG (W7 and W18) in the ddl-6 background were assayed for the susceptibility to Pst DC3000.",
    "ncbi_link": "DDL: 821601
ddl: 821601"
  },
  {
    "caption": "(A) flg22-induced callose deposition is reduced in ddl-6 and parp1,2. Leaves of four-week-old plants were inoculated with 0.5 µM flg22 for 20 hr or hrcC at OD600=0.2 for 24 hr and stained with aniline blue. Callose deposits were visualized under UV light and quantified by Image J. The data are shown as mean ± SE (n=12). Bar=100 µm.",
    "ncbi_link": "ddl: 821601
hrcC: 1183025
parp1: 817690"
  },
  {
    "caption": "(B) The hrcC-mediated induction of some late responsive genes is compromised in the ddl-6 and parp1,2 mutants. Fully expanded leaves of four-week-old plants were hand-inoculated with hrcC(OD600=0.5), and collected at 0, 3 and 24 hpi for qRT-PCR. The data are shown as mean ± SE from three independent repeats.",
    "ncbi_link": "ddl: 821601
hrcC: 1183025
parp1: 817690"
  },
  {
    "caption": "(C) Pst DC3000-induced PR1and PR5transcripts are blocked in ddl-6 and parp1,2. Fully expanded leaves of four-week-old plants were inoculated with Pst DC3000 (OD600=0.01), and collected at 0, 8 and 24 hpi for qRT-PCR. The data are shown as mean ± SE from three independent repeats.",
    "ncbi_link": "ddl: 821601
parp1: 817690
PR1: 815949
PR5: 843842"
  },
  {
    "caption": "(D) flg22-induced MAPK activation in Col-0 and ddl-6. Ten-day-old seedlings were treated with 100 nM flg22 and collected at the indicted time points. MAPK activation was analyzed by an immunoblot (IB) with -pERK antibody (top panel), and the protein loading is shown by Ponceau S staining for RuBisCo (RBC) (bottom panel).",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(E) flg22-induced ROS in Col-0 and ddl-6. Leaf discs from four-week-old plants were assayed for ROS production upon 100 nM flg22 treatment over 30 min. The data are show as mean± SE (n=24).",
    "ncbi_link": "ddl: 821601"
  },
  {
    "caption": "(A) PARP2 and DDL association in Arabidopsis protoplasts. PARP2-HA and DDL-FLAG were transiently expressed in Col-0protoplasts, immunoprecipitated with α-FLAG antibody (IP: -FLAG), and immunoblotted with α-HA (IB: α-HA) or α-FLAG antibody (IB: -FLAG) (top two panels). The protein inputs are shown with immunoblotting before immunoprecipitation (bottom two panels). Protoplasts were treated without or with 100 nM flg22 for 30 min.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(B) PARP2 and DDL association in N. benthamiana. PARP2-FLAG and DDL-HA were transiently co-expressed in leaves of N. benthamiana. The samples were collected at 2 dpi for Co-IP assay with 100nM flg22 treatment for 1 hr.",
    "ncbi_link": "PARP2: 828049"
  },
  {
    "caption": "(D) PARP2 and DDL interaction in vitro. GST-PARP2 protein immobilized on glutathione beads was used to pull-downHIS-SUMO-DDL-HA proteins (left panels). A PARylation reaction was performed prior to the pull-down assay (the third lane of left panels). The PARylated PARP2 and DDL were detected with α-PAR antibody (right panels).",
    "ncbi_link": "PARP2: 828049"
  },
  {
    "caption": "(E) In vitro PARylation of DDL by PARP2. Immunoprecipitated DDL-FLAG proteins from Arabidopsis protoplasts were incubated with GST-PARP2 in a PARylation reaction containing Biotin-NAD+. The reactions in lane 4 and 5 contained 1 mM 3-AB or GST-PARG1 respectively. PARylated proteins were detected by streptavidin-HRP antibody (Strep), which recognizes Biotin-labelled PAR.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(A) flg22 stimulates DDL PARylation. DDL-FLAG was transiently expressed in Arabidopsis protoplasts fed with 32P-NAD+. Protoplasts were treated without or with 100 nM flg22 for 30 min. PARylated DDL was immunoprecipitated with α-FLAG affinity beads, separated on 10% SDS-PAGE and visualized by autoradiography. PAR(DDL) indicates PARylated DDL proteins. A representative result from three repeats is shown.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(B-C) DDL PARylation is reduced in parp1, parp2 and parp1,2 mutants. Protoplasts isolated from parp1or parp2 single mutants (B), or parp1,2 double mutants (C) were used for in vivo PARylation assay with 32P-NAD+. Protoplasts were treated with 100 nM flg22 for 30 min. The experiments were repeated twice with similar results.",
    "ncbi_link": "DDL: 821601
parp1: 817690
parp2: 828049"
  },
  {
    "caption": "(A) DDL-N but not DDL-C associates with PARP2. FLAG-tagged DDL-N or DDL-C was co-expressed with PARP2-HA in protoplasts for Co-IP assay. Protoplasts were treated without or with 100 nM flg22 for 30 min.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(B) in vivo PARylation of DDL-N or DDL-C in protoplasts fed with 32P-NAD+. PARylation was visualized with autoradiography.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(C) In vitro PARylation of DDL-N or DDL-C. FLAG-tagged DDL-N or DDL-C was expressed and immunoprecipitated from Arabidopsis protoplasts and subjected to in vitro PARylation by GST-PARP2 with Biotin-NAD+. PARylated proteins were detected by streptavidin-HRP antibody.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(F) DDL12E mutants substantially diminish its PARylation in vivo. In vivo PARylation of DDL12E1 or DDL12E2 was performed using Arabidopsis protoplasts fed with 32P-NAD+.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(G) Reduced association of DDL12E1 with PARP2 in protoplasts. Protoplasts were treated with 100 nm flg22 for 30 min before Co-IP assay.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(A) Phenotype of plants complemented with WT DDL or DDL12E1. Four-week-old plants of two independent transgenic lines of pDDL::DDL-FLAG (W7 and W18) or pDDL::DDL12E1-FLAG(E11 and E15) were photographed. Bar=1cm.",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(A) Phenotype of plants complemented with WT DDL or DDL12E1. Four-week-old plants of two independent transgenic lines of pDDL::DDL-FLAG (W7 and W18) or pDDL::DDL12E1-FLAG(E11 and E15). The expression of transgene was determined by an α-FLAGimmunoblot (bottom).",
    "ncbi_link": "DDL: 821601"
  },
  {
    "caption": "(C) PR1 and PR5 induction in transgenic lines. Leaves of four-week-old plants were inoculated with Pst DC3000 (OD600=0.01), and collected at 0, and 24 hpi for qRT-PCR analysis. The data in B and C are shown as mean ± SD (n=3) from three independent repeats with one-way ANOVA analysis and Tukey test (p<0.05). Different letters indicate significant differences.",
    "ncbi_link": "PR1: 815949
PR5: 843842"
  },
  {
    "caption": "D: U2-OS cells were transfected with non-targeting (mock) or TSG101-targeting siRNAs and irradiated (20 Gy) 90 min. before analysis. Lysates were analyzed by EMSA and results of fold changes in densitometric measurements of the three independent experiments were compared with an ordinary one-way ANOVA (*p < 0.05) in the right panel.",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "A: Nuclear-cytoplasmic fractionation of U2-OS cells. Indicated samples were transfected with siRNAs against TSG101. PARylation was inhibited by olaparib (10 µM, 24 hours before analysis). Cytoplasmic export of p-ATM was induced by etoposide (50 µM, 45 minutes before analysis). Nuclear and cytoplasmic fractions were immunoblotted with the indicated antibodies. The fractionation efficiency was controlled by the respective subcellular marker proteins (PARP1 and LDH-A). PARylation was detected using the Pan ADPr reagent. Note that PARylation is activated by shearing forces during extract preparation (lane 1)",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "B: U2-OS cells were transfected with non-targeting (-) or TSG101-targeting (+) siRNAs and cells were irradiated (+) or not (-) as indicated (20 Gy) 10 min. before analysis. Whole-cell extracts were immunoblotted with the 10H PAR monoclonal antibody.",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "D: U2-OS cells were transfected with non-targeting or VPS28-targeting siRNAs. Whole-cell extracts were immunoblotted with indicated antibodies.",
    "ncbi_link": "VPS28: 51160"
  },
  {
    "caption": "A: Proximity ligation assay (PLA) assay with unstimulated, etoposide (Eto)-treated (50 µM, 10 min. before analysis), or etoposide plus olaparib-(Olap) co-treated (50 µM of etoposide, 10 min. before analysis and 10 µM of olaparib 24 hours before analysis) U2-OS cells. The red dots represent PARP1-TSG101 interaction. The nucleus is stained with DAPI (blue). Scale bar: 10 µm. As negative controls, PLA was performed without primary PARP1 or TSG101 antibodies. As an additional control, PLA was performed in PARP1 depleted cells to show specificity B: Quantification of PLA dots per nuclei in A. Blind counting was performed from 30 replicates three biologically independent experiments. The conditions were compared with an ordinary one-way ANOVA (ns, p > 0.05; *p < 0.05; ***p < 0.001; ****p < 0.0001).",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "C: U2-OS cells were cotransfected with the indicated deletion constructs of mCherry-tagged TSG101 and EGFP-tagged PARP1. Immunoprecipitation of GFP was performed using whole-cell extracts.",
    "ncbi_link": "EGFP: 
mCherry: 
PARP1: 142
TSG101: 7251"
  },
  {
    "caption": "B: Representative images of PARP1-GFP association with laser-microirradiation sites in untreated (mock), olaparib-treated (10 µM, 24 hours before analysis) or siTSG101-transfected U2-OS cells at indicated times post-irradiation. Scale bar: 7.5 µm. The image is representative of nine replicates from three biologically independent experiments. Go to Movies EV1-3 for further illustration.",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "C: Cells were transfected with non-targeting or TSG101-targeting siRNAs. Immunofluorescence staining was performed with the indicated antibodies (red: cleaved caspase 3; green: γH2AX). Nuclei were stained with DAPI (blue). The image is a representative of 3 biologically independent experiments. Scale bar: 30 µm. See Fig EV6D for percentage of γH2AX positive cells as an evidence of IR-treatment. D: Percentage of cleaved caspase 3 was determined by blind counting of approximately 100 cells for each condition from 3 biologically independent experiments. Conditions were compared with an unpaired t-test (*p < 0.05, **p < 0.01).",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "E: γH2AX staining of TSG101-targeting or non-targeting siRNA transfected U2-OS cells reveals puncta-like foci at 2 or 7 days after irradiation.",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "A Immunoblot of endogenous BiP resolved by native-PAGE from lysates of CHO-K1 S21 wild-type (wt) or FICD-/- cells either transiently overexpressing wild-type FICD (high expression level; Hi) or mutant FICDE234G (E/G) or stably expressing recombinant wild-type FICD (low expression level; Lo). The cells in lanes 1-4 were mock transfected. Where indicated cells were exposed to cycloheximide (CHX; 100 µg/mL) for 3 h before lysis. Unmodified ('A') and AMPylated ('B') monomeric and oligomeric (II and III) forms of BiP are indicated. Immunoblots of the same samples resolved by SDS-PAGE report on FICD, total BiP and eIF2α (loading control). Data representative of four independent experiments are shown.",
    "ncbi_link": "FICD: 100760999"
  },
  {
    "caption": "B Wild-type FICD forms homomeric complexes in vivo. Immunoblots of orthogonally-tagged wild-type and Leu258Asp mutant FICD in the input cell lysate and following recovery by pull-down with streptavidin (recognising the AviTag) or anti-FLAG antibody. Proteins were detected with fluorescently-labelled streptavidin (StrepIR800) or FLAG antibody. Data representative of three independent experiments are shown.",
    "ncbi_link": "FICD: 11153"
  },
  {
    "caption": "C Immunoblot of endogenous BiP from transfected CHO-K1 S21 FICD-/- cells (as in A). Note that cells expressing monomeric FICDL258D accumulate AMPylated BiP. Data representative of three independent experiments are shown.",
    "ncbi_link": "FICD: 100760999"
  },
  {
    "caption": "E Comparison of the signal-averaged sedimentation coefficients of wild-type (red) and monomeric mutant FICDL258D (blue), as measured by analytical ultracentrifugation. A fit for monomer-dimer association (solid red line), constrained using the average value for the monomeric protein (dashed line, 2.82 S, Sw,20 = 3.02 S), yielded a Kd of 1.2 nM with a 95% confidence interval between 1.1 to 1.4 nM and a value of 4.08 S for the dimer (Sw,20 = 4.36 S). The fitted data points are from three independent experiments.",
    "ncbi_link": "FICD: 11153"
  },
  {
    "caption": "Quantification of bound GFP-Rad54 (10 nM) signal intensity for Rad51-ssDNA molecules with and without bound mCherry-Rdh54 (10 nM). Error bars represent s.d. of individual ssDNA molecules (N = 21).",
    "ncbi_link": "mCherry: 
Rdh54: 852365"
  },
  {
    "caption": "Quantification of GFP-Rad54 binding in the absence and presence of mCherry-Rdh54. The data was fit by non-linear regression and error bars represent s.d. of individual molecules (N = 43).",
    "ncbi_link": "mCherry: 
Rdh54: 852365"
  },
  {
    "caption": "Quantification of mCherry-Rdh54 binding in the absence or presence of GFP-Rad54. The data was fit by non-linear regression and error bars represent s.d. of individual molecules (N = 43).",
    "ncbi_link": "GFP: 
Rad54: 852713"
  },
  {
    "caption": "Widefield images of Atto565-labeled PSCs (magenta) bound to dsDNA curtains stained with YOYO1 (green). The PSCs were prepared with the indicated combinations of Rad51, Rdh54 and GFP-Rad54.   Number of Atto565-labeled PSC binding events per dsDNA molecule for PCS prepared with Rad54 and Rdh54 only (minus Rad51 ; N = 372), Rad51 plus Rad54 only (N= 117), Rad51 plus Rdh54 only (N = 258), Rad51 plus Rdh54 and Rad54 (N = 303). The error bars represent the s.d. for three independent experiments.  ",
    "ncbi_link": "GFP: 
Rad51: 856831
Rad54: 852713
Rdh54: 852365"
  },
  {
    "caption": "Translocation velocities for tailed duplex PSCs prepared with Rad54 only (lane 1; N = 86), Rad54 plus Rdh54 (lane 2; N = 144), Rad54-K341R plus Rdh54 (lane 3; N = 47), Rad54 plus Rdh54-K318R (lane 4; N = 112), or Rad54-K341R plus Rdh54-K318R (lane 5; N = 64). The error bars represent s.d.   Translocation distances for tailed duplex PSCs prepared with Rad54 only (lane 1; N = 86), Rad54 plus Rdh54 (lane 2; N = 144), Rad54-K341R plus Rdh54 (lane 3; N = 47), Rad54 plus Rdh54-K318R (lane 4; N = 112), or Rad54-K341R plus Rdh54-K318R (lane 5; N = 64). Error bars were generated by bootstrapping.   First passage recognition efficiency for tailed duplex PSCs prepared with Rad54 only (lane 1; N = 145), Rad54 plus Rdh54 (lane 2; N = 115), Rad54-K341R plus Rdh54 (lane 3; N = 45), Rad54 plus Rdh54-K318R (lane 4; N = 39), or Rad54-K341R plus Rdh54-K318R (lane 5; no translocation observed). Error bars (s.d.) were generated from three independent experiments.   ",
    "ncbi_link": "Rad54: 852713
Rdh54: 852365"
  },
  {
    "caption": "PSC binding distributions following 10 min reactions for PSCs prepared with Rad54 plus Rdh54 (N= 181); Rad54 plus Rdh54-K318R (N= 115); Rad54-K341R plus Rdh54 (N = 90); or Rad54-K341R plus Rdh54­-K318R (N = 54), as indicated. Error bars were generated by bootstrapping. The asterisks denote the targeted region of homology on the donor dsDNA molecules.",
    "ncbi_link": "Rad54: 852713
Rdh54: 852365"
  },
  {
    "caption": "Yeast spot growth assays to monitor the ability of Rad54, Rdh54, Rad54NRdh54, and Rdh54NRad54 to complement MMS sensitivity in rad54∆ yeast strains.   Yeast spot growth assays to monitor the ability of Rad54, Rdh54, Rad54NRdh54, and Rdh54NRad54 to complement MMS sensitivity in rdh54∆ yeast strains.   ",
    "ncbi_link": "rad54: 852713
rdh54: 852365"
  },
  {
    "caption": "(B-C) Representative time-lapse images of (B) Tet1-3 triple KD (Tet-TKD), (C) Tet3-KD and control embryos at 3.5 days post fertilization. Scale bar = 100 µm.",
    "ncbi_link": "Tet1: 52463
Tet3: 194388
Tet: 194388///214133///52463"
  },
  {
    "caption": "(D-E) Developmental rates of (D) control (control-MO injected), Tet1-, Tet2- and Tet3-single KD and Tet-TKD embryos and (E) control (control-MO + Tet2 mRNA co-injected), Tet2-KD2 (Tet2 MO2 injected), Tet2-KD2 + GFP mRNA and Tet2-KD2 + Tet2 mRNA embryos until blastocyst stage. Indicated p-values were calculated using log rank (Mantel-Cox) test against (D) control embryos or (E) Tet2-KD2 embryos or as indicated (ns = non-significant, * = p < 0.05, **** = p < 0.0001; numbers of analyzed embryos for each condition are indicated in parenthesis).",
    "ncbi_link": "GFP: 
Tet1: 52463
Tet2: 214133
Tet3: 194388
Tet: 194388///214133///52463"
  },
  {
    "caption": "(A-B) Representative images of (A) 5hmC- and (B) 5mC and 5caC-IF of control (control-MO injected), Tet1+2-DKD and Tet-TKD zygotes at 12 hpf. Paternal and maternal pronuclei are indicated, Pb = polar body; Sp = sperm; Scale bar = 20 μm.",
    "ncbi_link": "Tet1: 52463
Tet: 194388///214133///52463"
  },
  {
    "caption": "(B) MA plots of RNA-seq data from Tet3-KD/control (left) and Tet-TKD/control (right) 2-cell embryos. Significant differentially expressed genes are colored. The amount of up- and downregulated genes is indicated. Differentially expressed genes were determined using DEseq2 (padj<0.05, |log2FC|>0.7).",
    "ncbi_link": "Tet3: 194388
Tet: 194388///214133///52463"
  },
  {
    "caption": "(A) Expression changes of different classes of TEs in Tet3-KD and Tet-TKD. Shown are log2-fold changes of KD embryos compared to control 2-cell embryos of different repetitive elements subdivided in classes of TEs. Indicated p-values were calculated using a paired two-tailed t-test (*** = p < 0.001, **** = p <0.0001, data are represented as medium smoothed violin plots with indicated median and quartiles as dotted lines).",
    "ncbi_link": "Tet: 214133///52463///194388
Tet3: 194388"
  },
  {
    "caption": "(B-C) Expression levels of (B) maternally expressed ERV3-LTRs and (C) 2-cell embryo specific ERV3-LTRs in control, Tet3-KD and Tet-TKD 2-cell embryos (p-values were calculated using DEseq2; * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001, data are represented as mean ± SD, dots represent single embryos).",
    "ncbi_link": "Tet: 214133///52463///194388
Tet3: 194388"
  },
  {
    "caption": "(E) Expression levels of important candidate factors in control, Tet3-KD and Tet-TKD 2-cell embryos, implicated in the generation of 2C-like cells and as important regulators of EGA (p-values were calculated using DEseq2; * = p < 0.05, ** = p < 0.01, **** = p < 0.0001, data are represented as mean ± SD, dots represent single embryos).",
    "ncbi_link": "Tet: 214133///52463///194388
Tet3: 194388"
  },
  {
    "caption": "(A) % CpG methylation of 20 kb tiles in 5% bins in control or Tet-TKD 2-cell embryos. All samples from one condition were merged for this visualization.",
    "ncbi_link": "Tet: 194388///214133///52463"
  },
  {
    "caption": "(H) Developmental rate of embryos derived from control, Tet2-MO2, Tet2-MO2 + Tet2 full-length mRNA (as shown in Fig. 1E) and Tet2-MO2 + Tet2 truncated mRNA (no catalytical domain) injected oocytes. Indicated p-values were calculated using the log rank (Mantel-Cox) test against Tet2-MO2 KD or as indicated (* = p < 0.05, *** = p < 0.001, **** = p < 0.0001, numbers of analyzed embryos for each condition is indicated in parenthesis).",
    "ncbi_link": "Tet2: 214133"
  },
  {
    "caption": "(A) Immunoblot of protein lysates from wild-type, PERK-KO and GCN2-KO MEF cells incubated in the presence of DMSO (Control), Tunicamycin (0.1 µg/ml), or starved in EBSS for 16 h. Data are representative of three independent experiments.",
    "ncbi_link": "PERK: 13666
GCN2: 27103"
  },
  {
    "caption": "(B-D) Wild-type (B), GCN2-KO (C), and PERK-KO (D) MEF cells incubated in the presence of DMSO (Control) or Tunicamycin (0.1 µg/ml) as indicated in (A). Cells were fixed, permeabilized and stained with antibodies against TFE3 (green) and CHOP (red). Scale bar, 10 µm. Data are representative of three independent experiments.(E-F) Quantification of the percentage of MEF cells with nuclear TFE3 upon DMSO (Control), Tunicamycin treatments for 16 h (E), or starvation for 2 h (F) (mean ± SD of three independent experiments, one-way ANOVA analysis versus DMSO treated cells, ns= not significant, ***p < 0.001; n>400 cells per condition).",
    "ncbi_link": "PERK: 13666
GCN2: 27103"
  },
  {
    "caption": "(G) Quantification of phospho-4EBP1 protein levels in wild-type and GCN2-KO MEF cells upon starvation for 2 h (the mean ± SD of the fold increase of the phospho-4EBP1 to total 4EBP1 ratio from three independent experiments, one-way ANOVA analysis versus starvation treated wild-type cells, ***p < 0.001).",
    "ncbi_link": "GCN2: 27103"
  },
  {
    "caption": "(A) ARPE-19 cells infected with either adenovirus expressing TFE3-WT-Myc or TFE3-S321A-Myc for 16h. Cells were fixed, permeabilized and stained with antibodies against Myc. Scale bar, 10 µm. Quantification of the percentage of ARPE-19 cells with nuclear TFE3-Myc (means ± SD of 3 independent experiments, students t-test, ****p < 0.0001; n>400 cells per condition).",
    "ncbi_link": "TFE3: 7030"
  },
  {
    "caption": "(G) Quantification of the percentage of calcineurin depleted ARPE-19 cells with nuclear TFE3 upon Tunicamycin (Tun.) or Starvation (Strv.) treatments for 16 h (mean ± SD of three independent experiments, one-way ANOVA analysis versus siNon-target treated cells within the indicated treatment, ns= not significant, *p < 0.05, **p < 0.01, ***p < 0.001; n>400 cells per condition).",
    "ncbi_link": "calcineurin: "
  },
  {
    "caption": "(H) Immunoblots of protein lysates from ARPE-19 cells depleted of Calcineurin catalytic subunits PPP3CA and PPP3CB. Data are representative of three independent experiments.",
    "ncbi_link": "Calcineurin: 
PPP3CA: 5530
PPP3CB: 5532"
  },
  {
    "caption": "(I) Relative Quantitative Real-Time PCR analysis of PPP3CA and PPP3CB mRNA transcript levels in ARPE-19 cells depleted of Calcineurin catalytic subunits PPP3CA and PPP3CB (mean ± SD of the RNA fold change of indicated gene mRNAs normalized to actin mRNA from three independent experiments, one-way ANOVA analsysis versus the siNon-Target (siNT) treated cells, ***p < 0.001).",
    "ncbi_link": "actin: 
Calcineurin: 
PPP3CA: 5530
PPP3CB: 5532"
  },
  {
    "caption": "(J) Quantification of the percentage of ATF4 depleted ARPE-19 cells with nuclear TFE3 upon Tunicamycin treatment for 16 h (mean ± SD of two independent experiments, one-way ANOVA analysis versus siNon-target treated cells within the indicated treatment***p < 0.001; n>400 cells per condition).",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "(A) Relative Quantitative Real-Time PCR analysis of TFEB and TFE3 mRNA transcript levels in ARPE-19 cells depleted of TFEB and TFE3 (mean ± SD of the RNA fold change of indicated gene mRNAs normalized to actin mRNA from three independent experiments, student's t-test versus siNon-Target (siNT) treated cells, ***p < 0.001).",
    "ncbi_link": "actin: 
TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "(B) Relative Quantitative Real-Time PCR analysis of MCOLN1, ATP6V1C1, HEXA and UVRAG mRNA transcript levels in ARPE-19 cells depleted of TFEB and TFE3 upon incubation with DMSO (Control) or Tunicamycin (5 µg/ml) for 16 h (mean ± SD of the RNA fold change of indicated gene mRNAs normalized to actin mRNA from three independent experiments, one-way ANOVA analysis versus the same treatment condition in the siNon-Target (siNT) treated cells or versus the DMSO condition in siNon-Target (siNT) treated cells, *p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "actin: 
ATP6V1C1: 528
HEXA: 3073
MCOLN1: 57192
TFE3: 7030
TFEB: 7942
UVRAG: 7405"
  },
  {
    "caption": "(A) Immunoblots of protein lysates from ARPE-19 cells infected with either adenovirus expressing Null, TFEB-S211A, or TFE3 upon incubation with DMSO (Control), Tunicamycin (5 µg/ml) or starved in EBSS for 16 h. Data are representative of five independent experiments.(B) Quantification of ATF4, CHOP and GADD34 protein levels in ARPE-19 cells treated as indicated in (A) (mean ± SD of the fold change of the indicated protein to actin ratio from three independent experiments, one-way ANOVA analysis versus the corresponding treatment condition in the adenovirus-Null infected cells, *p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "TFE3: 7030
TFEB: 7942"
  },
  {
    "caption": "(C) Relative Quantitative Real-Time PCR analysis of ATF4, CHOP, GADD34 and MCOLN1 mRNA transcript levels in ARPE-19 cells treated as indicated in (A) (mean ± SD of the RNA fold change of indicated genes normalized to actin mRNA from three independent experiments, one-way ANOVA analysis versus the corresponding treatment condition in the adenovirus-Null infected cells, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "actin: 
ATF4: 468
CHOP: 1649
MCOLN1: 57192
GADD34: 23645"
  },
  {
    "caption": "(A-D) Relative Quantitative Real-Time PCR analysis of ATF4 (A), ASNS (B), CAT1 (C) and xCT (D) mRNA transcript levels in ATF4-depleted ARPE-19 cells infected with either adenovirus expressing Null or TFEB-S211A upon incubation with DMSO (Control), Tunicamycin (5 µg/ml), or starved in EBSS for 16 h (mean ± SD of the RNA fold change of indicated gene mRNAs normalized to actin mRNA from three independent experiments, one-way ANOVA analysis versus the corresponding treatment condition in the adenovirus-Null infected and siRNA Non-Target (siNT) treated cells, *p < 0.05, ***p < 0.001).",
    "ncbi_link": "actin: 
ASNS: 440
ATF4: 468
CAT1: 6541
xCT: 23657
TFEB: 7942"
  },
  {
    "caption": "(E) ChIP-qPCR analysis of the ATF4 promoter and 2000bp upstream of the region of interest (ATF4-Control) from MEF cells that were untreated (control), starved for 2 h, or treated with Tunicamycin (0.1 µg/ml) for 16 h. Amplification regions are indicated by arrows. Chromatin DNA was immunoprecipitated with antibodies for anti-TFE3. Bar graphs show the amount of immunoprecipitated DNA detected by the real-time PCR assay. Values were normalized to the input and plotted as relative enrichment compared to untreated conditions (means ± SD of three independent experiments, students t-test, *p < 0.05, **p < 0.01).",
    "ncbi_link": "ATF4: 11911"
  },
  {
    "caption": "(F) Relative Quantitative Real-Time PCR analysis of SUMF1, DERL1, ATF6, APEX1 and GPX1 mRNA transcript levels in ARPE-19 cells infected with either adenovirus expressing Null or TFEB-S211A (mean ± SD of the RNA fold change of indicated gene mRNAs normalized to actin mRNA from three independent experiments, students t-test, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "actin: 
APEX1: 328
ATF6: 22926
DERL1: 79139
GPX1: 2876
SUMF1: 285362
TFEB: 7942"
  },
  {
    "caption": "(G) Immunoblots of protein lysates from ARPE-19 cells infected with either adenovirus expressing Null or TFEB-S211A. Data are representative of three independent experiments.(H) Quantification of IRE1α and APEX1 protein levels in ARPE-19 cells infected as indicated in (G) (mean ± SD of the fold increase of the indicated protein to actin ratio from three independent experiments, students t-test, ***p < 0.001).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A) Immunoblots of protein lysates from Null- or TFEB/3 knockout-MEF cells incubated in the presence of DMSO (Control) or Tunicamycin (Tun.) (0.1 µg/ml) for the indicated times. Data are representative of three independent experiments.(B) Quantification of ATF4 protein levels in Null- or TFEB/3 knockout-MEF cells treated as indicated in (A) (mean ± SD of the ATF4 to actin protein ratio from three independent experiments, student's t-test versus the corresponding time point in Null-MEF cells, ns= not significant, **p < 0.01).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(C) Cell viability was determined in Null- or TFEB/3 knockout-MEF cells incubated in the presence of DMSO (Control) or Tunicamycin (Tun.) (0.1 µg/ml) for the indicated times (mean ± SD of the percentage of viable cells compared to control from three independent experiments, one-way ANOVA analysis versus the corresponding time point in Null-MEF cells ***p < 0.001).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(D) Chromatin condensation, an indication of cells undergoing apoptosis, was assessed in Null- or TFEB/3 knockout-MEF cells incubated in the presence of DMSO (Control) or Tunicamycin (0.1 µg/ml) for the indicated times. Confocal microscopy images were obtained from fixed cells stained with Hoechst 33342. Scale bar, 20 µm. Data are representative of three independent experiments.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(E) Immunoblots of protein lysates from Null- or TFEB/3 knockout-MEF cells treated as described in (A). Data are representative of three independent experiments.(F-H) Quantification of CHOP (F), PUMA (G) and NOXA (H) protein levels in Null- or TFEB/3 knockout-MEF cells treated as indicated in (E) (mean ± SD of the indicated protein to actin ratio from three independent experiments, student's t-test analysis versus the corresponding time point in Null-MEF cells, ns= not significant, *p < 0.05, **p < 0.01).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(I) adenovirus of protein lysates from ARPE-19 cells infected with either adenovirus expressing Null, TFEB-S211A or TFE3. Data are representative of three independent experiments.(J) Quantification of PUMA protein levels in ARPE-19 cells infected as indicated in (I) (mean ± SD of the fold change of the indicated protein to actin ratio from three independent experiments, one-way ANOVA analysis versus the adenovirus-Null infected cells, *p < 0.05, ***p < 0.001).",
    "ncbi_link": "TFE3: 209446
TFEB: 21425"
  },
  {
    "caption": "(C and D) RNAi of CG34015 in the wing P-compartment significantly reduces the size in both sexes. The images are taken from female wings. Statistical significance was evaluated by Wilcoxon test.",
    "ncbi_link": "CG34015: 3885570"
  },
  {
    "caption": "(E) Genome-wide association of CG34015 expression. Manhattan plot shows a strong association of CG34015 RNA with X chromosome in both sexes. P-values are plotted against ordered SNPs along the genome. eQTLs associated with CG34015 are designated as red dots.",
    "ncbi_link": "CG34015: 3885570"
  },
  {
    "caption": "(F) Zoomed plot around the CG34015 gene region on X chromosome. eQTLs linked to CG34015 are mostly located upstream of the CG34015 gene region. The red arrow indicates the transcriptional direction.",
    "ncbi_link": "CG34015: 3885570"
  },
  {
    "caption": "(G) SNP variation of CG34015-linked eQTLs. SNP states at each eQTL are depicted for each line using different colors (grey dots: reference SNP, blue dots: alternate SNP with a negative effect on RNA level). Lines are ordered from left to right as CG34015 RNA levels increase. Note that the eQTLs are highly linked with each other.",
    "ncbi_link": "CG34015: 3885570"
  },
  {
    "caption": "(H and I) Segregation of CG34015 RNA levels and wing size (absCS) by the variation of an eQTL (X_16344746_SNP). P-values are shown. (J) Association of the eQTL (X_16344746_SNP) with population-wide, wing size variation among 143 DGRP lines. P-value and R2 are shown for each sex.",
    "ncbi_link": "CG34015: 3885570"
  },
  {
    "caption": "a, Survival curves  of wild type (n=27) and Cdc14  DKO (n=51) mice  during the first 6 weeks of life. (***, p<0.001; Log-rank, Mantel-Cox test). b, Representative images of postnatal day 9 Cdc14  DKO and wild-type littermates. c, Weight  of Cdc14  DKO and wild-type littermates during the first 3 weeks of life (n=4 per genotype). Data information: Bars indicate mean ± SEM. p>0.05; **, p<0.01; ***, p<0.001, Student's t-test with Welch's correction.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "d, Representative macroscopic pictures of brain  dorsal view of wild type (WT) and Cdc14  KO mice  at postnatal 0, 5 and 9 days (P0, P5 and P9). Scale bar, 2 mm. The bar plots show the quantification of brain  width, length and area, respectively. Data information: Bars indicate mean ± SEM. , *, p>0.05; **, p<0.01; ***, p<0.001, Student's t-test with Welch's correction. Non-significant data (p>0.05) are not labeled.In data show the individual data, average and SEM from 3 WT and 3 DKO mice.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "e, Representative cresyl violet staining  images of midsagittal sections of  cerebellar vermis  of WT and Cdc14  KO mice  at P0, P5 and P9. Fissures  underdeveloped in mutant samples are labeled with arrowheads. Scale bar, 700 μm. The bar plots show the quantification of the  cerebellar vermis  area, the number of folia  and the average length of the fissures, respectively. Data information: Bars indicate mean ± SEM. p>0.05; **, p<0.01; ***, p<0.001, Student's t-test with Welch's correction. Non-significant data (p>0.05) are not labeled.In data show the individual data, average and SEM from 3 WT and 3 DKO mice.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "g, Representative images of misdigital sections stained  with DAPI  (blue), Calbindin  (green) and GFAP  (red) of cerebellar vermis of wild-type ad Cdc14  DKO mice  at 9 days after birth. Scale bar, 50 μm. Plots show the quantification of Purkinje cell dendritic  length (average distance of 30 random measurements) and the number of cells per 100 μm from 3 different fields from 3 different mice  in each plot. Data information: Bars indicate mean ± SEM. , *, p>0.05; **, p<0.01; ***, p<0.001, Student's t-test with Welch's correction.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "a. Confocal microscopy  analysis of wild-type and Cdc14  DKO embryonic stem cells (ESCs) subjected to neural differentiation. Neuronal  marker TUJ1  (green), glial  marker GFAP  (red) and nuclear  marker DAPI  (blue) are stained  and quantified after 18 days in differentiation  media. Each dot represents the ratio between TUJ  or GFAP  and DAPI  area in an image containing at least 100 cells from 4 independent experiments with two different clones. **** p-value<0.0001. Student's t-test. Scale bar 50 μm.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "c, Confocal microscopy analysis of WT and Cdc14  DKO ESC  subjected to neural differentiation. Neural progenitor marker Nestin  was stained  and quantified after 6 days in differentiation  media. Each dot represents the ratio between Nestin  and DAPI  area in an image containing at least 100 cells. ****, p<0.0001; Students' t-test.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "d, Western blot  analysis of CDC14B-GFP co-immunoprecipitations. HeLa  cells were transfected with UTF1  and GFP  or CDC14B-GFP. Cytoplasmic  and nuclear  soluble proteins were extracted with RIPA, and nucleolar  and chromatin-bound proteins were extracted with  high salt RIPA. Immunoprecipitations  with anti-GFP  antibody were performed. Total protein extracts and immunoprecipitates  were loaded and UTF  (upper panel) and GFP  (lower panel) were blotted.",
    "ncbi_link": "GFP: 
CDC14B: 8555
UTF1: 22286"
  },
  {
    "caption": "e, Immunoprecipitation  of UTF1  upon co-transfection with CDC14B. Total protein was extracted with high-salt RIPA and immunoprecipitations  with anti-UTF1  antibody were performed.",
    "ncbi_link": "CDC14B: 8555"
  },
  {
    "caption": "f, Expression  of active CDC14B, but not a phosphatase-dead (PD) isoform, reduces slow-mobility bands of UTF1. Vinculin  was used as a loading control.",
    "ncbi_link": "CDC14B: 8555"
  },
  {
    "caption": "a,  Quantitative RT-PCR in wild-type (WT) or Cdc14  DKO ESCs  of the indicated transcripts during neural  differentiation. n=3 independent experiments (±S.E.M.); *, p<0.05; **, p<0.01; ***, p<0.001; Student's t-test.",
    "ncbi_link": "Cdc14: 218294///229776"
  },
  {
    "caption": "c,  Confocal microscopy  analysis of UTF1  intensity in WT and Cdc14  DKO ESCs  at time  0 (T0) and after 1 day (T1) in differentiation media. The quantification of UTF1  fluorescence mean intensity (FMI) per cell is shown in the plot to the right. Figures and horizontal bars indicate mean ± S.E.M. (n=1269 WT T0 cells, n=2726 WT T1, n=974 Cdc14  DKO T0, n=1173 Cdc14  DKO T1). **, p<0.01; ****, p<0.0001; Student's t-test with Welch's correction.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "d, Western blot analysis of UTF1  expression in WT and Cdc14  DKO ESCs  at time  0 and after 3 days in differentiation media.",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "e, Western blot  analysis of UTF1  expression in WT and Cdc14  DKO ESCs  in absence or presence of the kinase  inhibitors roscovitine  (R) or trametinib  (T).",
    "ncbi_link": "Cdc14: 229776///218294"
  },
  {
    "caption": "f, Immunoblot  analysis of UTF1  protein stability after transfection of HeLa  cells with UTF1  and GFP  or CDC14B-GFP. Cells were treated with cycloheximide  (CHX) and total proteins were detected at different time points  as indicated. Cyclin B1  and β-catenin  are used as controls.",
    "ncbi_link": "GFP: 
CDC14B: 8555
UTF1: 22286"
  },
  {
    "caption": "g, Western blot  analysis of UTF1  WT or mutants in three (UTF1-3KR) or five (UTF1-5KR) lysines in absence or presence of trametinib  (T) or roscovitine  (R).",
    "ncbi_link": "UTF1: 22286"
  },
  {
    "caption": "h, Immunoblot  of UTF1  mutants in SPOP, SIAH   or SPOP+SIAH   potential binding sites, as well as S48D and S54D phosphorylation sites. Actin  was used as a loading control.",
    "ncbi_link": "UTF1: 22286"
  },
  {
    "caption": "Gene-trap-based genetic screen in haploid human  cells for regulators of p38     kinase activation (p38 Thr180/Tyr182 phosphorylation) in response to hyperosmotic shock (500 mM Sorbitol, 1 h). Per gene (dots), the frequency of gene-trap insertions in the 'high' phospho-p38    population divided by the frequency of insertions in the 'low' population is plotted as mutation index (y-axis) against the total number of insertions assigned to the gene (x-axis). Significant negative and positive regulators are colored in orange and blue, respectively (two-sided Fisher's exact test, false discovery rate-corrected, p≤0.05).",
    "ncbi_link": "p38: 1432"
  },
  {
    "caption": "Human U2OS  cells and cells deleted for ZAK  (∆ZAK) were treated with anisomycin  (1 h) or 500 mM sorbitol  (1 h). Lysates were analyzed by immunoblotting as indicated.",
    "ncbi_link": "ZAK: 51776"
  },
  {
    "caption": "Unique gene-trap insertions (dots) mapped to the genomic ZAK  locus (x-axis) identified in the low (blue) and high (orange) channel of two individual haploid genetic screens for stress-induced p38  activation and Anisomycin(Brockmann et al., 2017)). The total number of identified insertions was similar for each channel within the individual screens. For visual purposes, insertion dots were spread on the y-axis and exons in the ZAK gene body schematic have been scaled up (compared to introns).",
    "ncbi_link": "ZAK: 51776"
  },
  {
    "caption": "U2OS/S-HA-ZAKβ  cells were induced for expression with doxycycline (DOX) and subjected to the indicated drugs and treatments (1 h). Lysates were analyzed by immunoblotting  with the indicated antibodies. Sorb., sorbitol; Ani., anisomycin; Ars., arsenite.",
    "ncbi_link": "HA: 
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  cells stably expressing WT and kinase-dead (KD) versions of S-HA-ZAKβ  were pre-treated with ZAK  inhibitor (ZAKi - 0.5 h) and 500 mM sorbitol  (1 h) as indicated. Whole Cell Extracts (WCE) were analyzed by immunoblotting, and strep-pulldown  material was used in a  kinase assay, separated by SDS-PAGE and analyzed by autoradiography.",
    "ncbi_link": "HA: 
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK cells rescued with S-HA-ZAKβ, were DOX-induced and treated with 500 mM sorbitol  (1 h) as indicated. Lysates were analyzed by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "HA: 
ZAK: 51776
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK cells were transfected with the indicated siRNAs and treated with sorbitol  (500 mM, 1 h) as indicated. Lysates were analyzed by immunoblotting  with the indicated antibodies. T1, TAK1; M2, MEKK2.",
    "ncbi_link": "ZAK: 51776
TAK1: 6885
MEKK2: 79109"
  },
  {
    "caption": "U2OS  cells stably expressing Strep-HA-ZAKβ  or -ZAKα  were treated with sorbitol  (500 mM, 1 h) as indicated. Cells were fixed, immunostained  with HA  antibody and counter-stained  with DAPI. Data information: scale bars, 10 μm.",
    "ncbi_link": "HA: 
ZAKα: 51776
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK cells stably expressing the indicated Strep-HA-tagged ZAKβ  constructs were treated with sorbitol  (500 mM, 5 min). Lysates were analyzed by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "HA: 
ZAK: 51776
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK  cells were embedded in agarose  and subjected to cyclic compression (0.5 h). Lysates were analyzed by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "ZAK: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK  cells stably expressing the indicated Strep-HA-tagged ZAKβ  constructs were embedded in agarose  and subjected to cyclic compression  for 5 or 30 min. Lysates were analyzed as in (B).",
    "ncbi_link": "HA: 
ZAK: 51776
ZAKβ: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK cells were pretreated with ZAK  inhibitor (ZAKi) for 30 min and subjected to equibiaxial  (Equi) or uniaxial  (Uni) cyclic stretch  (0.5 h) as indicated. Lysates were analyzed as in (B).",
    "ncbi_link": "ZAK: 51776"
  },
  {
    "caption": "U2OS  and ∆ZAK  cells were transfected with the indicated siRNAs and subjected to equibiaxial cyclic stretch (5 min) as indicated. Lysates were analyzed as in (B).",
    "ncbi_link": "ZAK: 51776"
  },
  {
    "caption": "Skeletal muscle (tibialis anterior, TA) and liver  from WT and ZAK-/- mice  were lysed and analyzed for ZAK  isoform expression  by immunoblotting. Ponceau staining of the membrane indicates equal loading.",
    "ncbi_link": "ZAK: 26409"
  },
  {
    "caption": "Mouse embryonic fibroblasts (MEF) isolated from WT and ZAK-/- mice  were treated with 500 mM sorbitol  (1 h). Lysates were analyzed by immunoblotting  with the indicated antibodies. *, unspecific band.",
    "ncbi_link": "ZAK: 26409"
  },
  {
    "caption": "16-18-week-old WT and ZAK-/- male mice  (n=3 biological replicates) were subjected to the protocol in (D). TA  lysates were analyzed by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "ZAK: 26409"
  },
  {
    "caption": "C2C12  cells were differentiated into myotubes  for 14 days and transfected with the indicated GFP-ZAKβ   constructs. Cells were fixed and immunostained  with an antibody against α-actinin1. Data information: scale bars, 20 μm.",
    "ncbi_link": "GFP: 
ZAKβ: 51776"
  },
  {
    "caption": "16-18-week-old WT and ZAK-/- male mice  were subjected to the experimental protocol in (I). TA muscle  lysates were analyzed by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "ZAK: 26409"
  },
  {
    "caption": "H&E staining  of soleus muscle cross sections from 8- and 22-week-old WT and ZAK-/- male mice. Arrows indicate the presence of centralized nuclei. Scale bars, 50 μm. Quantification of (A). Values indicate the percentage of fibers  displaying centralized nuclei and error bars represent the standard deviation (n=3 biological replicates). **, p<0.01 and ***, p<0.001 in t-test with Bonferroni-Dunn correction for multiple comparison.",
    "ncbi_link": "ZAK: 26409"
  },
  {
    "caption": "Fluorescent and histological analysis of liver morphology in WT and yap-/- mutant larvae on a lf:CFP background at 5 dpf. The blue colour overlay represents the fluorescent liver tissue. Scale bar: 200μm (bright field, BF) and 50μm (histology, H+E) Quantitative analysis of fluorescent liver area in WT and lf:Yap larvae at 5 dpf. n>30, ****p<0.0001, two-sided Student's t-test; values represent the mean ± standard error of the mean (s.e.m.)",
    "ncbi_link": "yap: 561411
Yap: 561411"
  },
  {
    "caption": "Whole-mount in situ hybridization (WISH) analysis of progenitor marker prox1, hhex, and foxa3 expression in WT and yap-/- mutant embryos at 36 hpf. Arrow and bracket highlight the hepatic bud. Scale bar: 200μm",
    "ncbi_link": "foxa3: 30559
hhex: 30098
prox1: 30679
yap: 561411"
  },
  {
    "caption": "qPCR analysis of hhex and prox1 gene expression in WT and yap-/- mutant embryos at 48 hpf. n>3, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "hhex: 30098
prox1: 30679
yap: 561411"
  },
  {
    "caption": "WISH analysis of prox1, hhex and foxa3 expression in WT, hs:dnYap and hs:Yap transgenic embryos heat shocked at 24 hpf and fixed at 36 hpf. Arrow and bracket highlight the hepatic bud. Scale bar: 200μm",
    "ncbi_link": "foxa3: 30559
hhex: 30098
prox1: 30679
Yap: 561411"
  },
  {
    "caption": "Quantitative analysis of hepatic bud area (prox1 staining) in WT, hs:dnYap and hs:Yap transgenic embryos heat shocked at 24 hpf and fixed at 36 hpf. n>10, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "Yap: 561411"
  },
  {
    "caption": "Fluorescent and histological analysis of liver morphology in dissected WT and yap-/- mutant adults on a lf:CFP background. The blue colour overlay represents the fluorescent liver tissue. Scale bar: 2mm (brightfield, BF) and 50μm (histology, H+E)",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Quantitative determination of body mass in WT and yap-/- adults. n=8, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m Quantitative determination of liver size in WT and yap-/- adults as determined by measuring liver mass as a percentage of body mass. n=12, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "qPCR analysis of the hhex expression in adult liver tissue isolated from WT and yap-/- fish. n>3, **p<0.01, two-sided Student's t-test; values represent the mean ± s.e.m qPCR analysis of the prox1 expression in adult liver tissue isolated from WT and yap-/- mutant fish. n>3, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "hhex: 30098
prox1: 30679
yap: 561411"
  },
  {
    "caption": "Heatmap of RNAseq analysis illustrating statistically significant differential gene expression between WT and yap-/- mutant larvae at 3 dpf. Blue indicates decreased expression, while red demonstrates increased expression",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Heatmap analysis of RNAseq data highlights the reduction of glucose transporters (glut1 and glut2) in yap-/- mutant larvae at 3 dpf",
    "ncbi_link": "glut1: 555778
glut2: 322493
yap: 561411"
  },
  {
    "caption": "qPCR analysis of glut1 and glut2 expression in WT and yap-/- mutant larvae at 3 dpf. n>3, *p<0.05, ***p<0.001, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "glut1: 555778
glut2: 322493
yap: 561411"
  },
  {
    "caption": "qPCR analysis of glut1 and glut2 expression in WT, hs:dnYap and hs:Yap transgenic embryos heat shocked at 24 hpf and isolated at 30 hpf. n>3, *p<0.05, **p<0.01, ****p<0.0001, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "glut1: 555778
glut2: 322493
Yap: 561411"
  },
  {
    "caption": "qPCR analysis of glut1 and glut2 expression in liver tissue dissected from WT, yap-/- mutant and lf:Yap transgenic adults. n>3, *p<0.05, **p<0.01, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "glut1: 555778
glut2: 322493
yap: 561411
Yap: 561411"
  },
  {
    "caption": "Glucose tolerance test in 3-month old WT and yap-/- mutant zebrafish. Blood glucose was measured 0, 30, 60, 120, 180 and 240 min post glucose injection. n>8, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m Glucose tolerance test in 12-month old WT and yap-/- mutant zebrafish. Blood glucose was measured 0, 30, 60, 120, 180 and 240 min post glucose injection. n>8, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Clustergram analysis of polar metabolite abundance from WT and yap-/- mutant larvae at 3 dpf as determined by LC-MS/MS via selected reaction monitoring (SRM) analysis. n=4, p<0.05, two-sided Student's t-test",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Steady state abundance of glycolytic intermediates in WT and yap-/- mutant larvae as determined by SRM analysis. n=4, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, two-sided Student's t-test; values represent the mean ± s.e.m Steady state abundance of nucleotides in WT and yap-/- mutant larvae as determined by SRM analysis. n=4, *p<0.05, ***p<0.001, ****p<0.0001, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Relative isotopic enrichment of 13C in glycolytic intermediates following incubation of WT and yap-/- mutant larvae in [U13C6]-glucose as determined by SRM analysis. n=3, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m Relative isotopic enrichment of 13C in nucleotide precursors following incubation of WT and yap-/- larvae in [U13C6]-glucose as determined by SRM analysis. n=3, *p<0.05, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Effect of nucleoside (NS) cocktail treatment from 1-3 dpf on the incidence of cardiac edema in WT and yap-/- mutant larvae. Each point represents the percentage of affected embryos in each independent clutch. n>7, **p<0.01, two-sided Student's t-test; values represent the mean s.e.m",
    "ncbi_link": "yap: 561411"
  },
  {
    "caption": "Effect of WZB-117 (WZB, 10 μM) treatment from 3-5 dpf in WT and lf:Yap larvae on liver size as determined by fluorescence microscopy at 5 dpf in lf:GFP reporters. Scale bar: 200μm",
    "ncbi_link": "Yap: 561411"
  },
  {
    "caption": "Dot plots showing the correlation between GLUT1 and YAP1 mRNA expression in the cancer cell line encyclopedia (CCLE, 967 lines). Pearson coefficient is 0.46 Dot plots showing the correlation between GLUT1 and AMOTL2 mRNA expression in the cancer cell line encyclopedia (CCLE, 967 lines). Pearson coefficient is 0.45",
    "ncbi_link": "AMOTL2: 51421
GLUT1: 6513
YAP1: 10413"
  },
  {
    "caption": "ChIPseq tracks at the GLUT1 locus highlighting YAP and TEAD enrichment overlaying H3K27Ac marks at an intragenic enhancer element in different contexts (LATS2 mutant MSTO211H cancer cells and HA-YAP5SA overexpressing HuCCT1 liver cancer cells)",
    "ncbi_link": "GLUT1: 6513
YAP: 10413"
  },
  {
    "caption": "Gross morphology of the liver from WT and TetONYap transgenic mice, treated with doxycycline for 10 days. Scale bar: 1 cm",
    "ncbi_link": "Yap: 22601"
  },
  {
    "caption": "Immunohistochemical analysis of GLUT1 expression in liver tissue from WT and TetONYap transgenic mice, treated with doxycycline for 10 days. Scale bar: 50μm",
    "ncbi_link": "Yap: 22601"
  },
  {
    "caption": "FDG PET imaging of coronal views from WT and TetONYap transgenic mice, treated with doxycycline for 10 days. Arrow is pointing to the liver",
    "ncbi_link": "Yap: 22601"
  },
  {
    "caption": "Scintillation analysis of FDG uptake (fraction of injected dose per gram of liver tissue, %ID/g) in dissected liver tissue from WT and TetON Yap transgenic mice, treated with doxycycline for 10 days. n=4, ***p<0.001, two-sided Student's t-test; values represent the mean ± s.e.m",
    "ncbi_link": "Yap: 22601"
  },
  {
    "caption": "A Hypocotyl lengths of wild-type and suc2 seedlings grown under continuous white light at 20 °C for 7 days or at 20 °C for 4 days followed by 3 days at 28 °C. The seedlings were grown on the medium with or without 3% sucrose. Representative seedlings are shown in the upper panel. Different letters above each box indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05; n = 10). Numbers indicate the ratio of hypocotyl lengths (28 °C/20 °C). In the box plots (A-D), the thick lines indicate median values, the lower and upper ends of the boxes represent the 25th and 75th percentiles, and the ends of the whiskers are set at 1.5 times the interquartile range.",
    "ncbi_link": "suc2: 838877"
  },
  {
    "caption": "B Hypocotyl lengths of wild-type and tps1-2;GVG::TPS1 seedlings grown under the same growth conditions Representative seedlings are shown in the upper panel. Different letters above each box indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05; n > 10). Numbers indicate the ratio of hypocotyl lengths (28 °C/20 °C).",
    "ncbi_link": "TPS1: 844194
tps1: 844194"
  },
  {
    "caption": "C Hypocotyl lengths of wild-type and tps1-2;GVG::TPS1 seedlings grown under continuous white light at 20 °C for 4 days followed by 3 days at 28 °C. The seedlings were grown on the medium containing either mock or 20 µM of dexamethasone (DEX). ns, not significant (Student's t-test P ≥ 0.05; n > 10). **P < 0.01 (Student's t-test); n > 10. Number indicates the ratio of hypocotyl lengths (Dex/Mock).",
    "ncbi_link": "tps1: 844194
TPS1: 844194"
  },
  {
    "caption": "D Hypocotyl lengths of wild-type and tps1-2;GVG::TPS1 seedlings grown in the dark at 20 °C for 7 days. Representative seedlings are shown in the left panel. ns, not significant (Student's t-test P ≥ 0.05; n > 10).",
    "ncbi_link": "TPS1: 844194
tps1: 844194"
  },
  {
    "caption": "F-I The qRT-PCR analyses of the transcript levels of YUC8, IAA19, IAA29, and PIF4. Transcript levels of each gene were normalized to those of PP2A and presented as values relative to those of wild-type seedlings at 20 °C. Error bars indicate s.d. (n = 3). Different letters above each bar indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05). Numbers indicate the ratio of transcript levels in seedlings grown at two different temperatures (28 °C/20 °C).",
    "ncbi_link": "IAA19: 820793
IAA29: 829361
PIF4: 818903
PP2A: 843333
YUC8: 828993"
  },
  {
    "caption": "A Western blotting with anti-PIF4 antibody shows that PIF4 protein levels are decreased in the tps1-2;GVG::TPS1 mutants compared to wild-type plants. Seedlings were maintained under 12-h light/12-h dark cycles at 20 °C for 4 days and then transferred under continuous light on the 5th day. The growth temperature was increased to 28 °C or kept at 20°C for 4 hours at ZT 20-24 before harvesting for total protein extraction. Equal loading of samples is shown by Ponceau S staining.",
    "ncbi_link": "TPS1: 844194
tps1: 844194"
  },
  {
    "caption": "B Western blotting showing the levels of PIF4-Myc protein in PIF4-OX and PIF4-OX;tps1-2;GVG::TPS1 seedlings. Total protein was extracted from the seedlings grown under continuous white light at 20 °C for 7 days or at 20 °C for 4 days followed by 3 days at 28 °C. Western blotting was probed using an anti-Myc antibody. Ponceau S staining is shown for equal loading.",
    "ncbi_link": "PIF4: 818903
tps1: 844194
TPS1: 844194"
  },
  {
    "caption": "A, B Hypocotyl lengths of wild-type and KIN10-OX seedlings grown under continuous white light at 20 °C for 7 days or at 20 °C for 4 days followed by 3 days at 28 °C. Representative seedlings are shown in (A). Numbers indicate the ratio of hypocotyl lengths (28 °C/20 °C). Different letters above each box indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05; n > 15). In the box plots, the thick lines indicate median values, the lower and upper ends of the boxes represent the 25th and 75th percentiles, and the ends of the whiskers are set at 1.5 times the interquartile range.",
    "ncbi_link": "KIN10: 821259"
  },
  {
    "caption": "C Transient gene expression assays. The reporter vector containing 35S::Renilla luciferase and IAA19p::Firefly luciferase was co-transfected with 35S::PIF4 and 35S::KIN10 into Arabidopsis mesophyll protoplasts. The activity of Firefly luciferase under the control of IAA19 promoter was normalized to that of Renilla luciferase. Error bars indicate s.d. (n = 4). Different letters above each bar indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05). T, 35S terminator.",
    "ncbi_link": "Firefly luciferase: 
Renilla luciferase: 
IAA19: 820793
KIN10: 821259
PIF4: 818903"
  },
  {
    "caption": "D Co-IP assays showing the interaction between PIF4 and KIN10 in vivo. Protein extracts from protoplasts expressing PIF4-Myc and KIN10-GFP (or GFP) were immunoprecipitated with anti-GFP antibody and analyzed by immunoblotting with anti-GFP or anti-Myc antibody.",
    "ncbi_link": "GFP: 
Myc: 
KIN10: 821259
PIF4: 818903"
  },
  {
    "caption": "KIN10 reduces the stability of PIF4 through 26S proteasome-mediated degradation. Transfected mesophyll protoplasts were pre-treated with or without 20 µM MG132 for 4 hours and then incubated in the presence of 100 µM cycloheximide (CHX) for the indicated time. Total protein was extracted from the protoplasts, and analyzed by immunoblotting with anti-GFP or anti-Myc antibody. Ponceau S staining is shown for equal protein loading. Representative western blots are shown in (B).",
    "ncbi_link": "KIN10: 821259
PIF4: 818903"
  },
  {
    "caption": "KIN10 reduces the stability of PIF4 through 26S proteasome-mediated degradation. Transfected mesophyll protoplasts were pre-treated with or without 20 µM MG132 for 4 hours and then incubated in the presence of 100 µM cycloheximide (CHX) for the indicated time. Total protein was extracted from the protoplasts, and analyzed by immunoblotting with anti-GFP or anti-Myc antibody. Quantification of relative PIF4-Myc levels is shown in (C). PIF4-Myc levels are presented as values relative to those at 0 h. In (C), different letters above each point indicate statistically significant differences (ANOVA and Tukey's HSD; P < 0.05; n = 3). Error bars indicate s.d. (n = 3).",
    "ncbi_link": "KIN10: 821259"
  },
  {
    "caption": "e, Western blotting analysis of PCM1 and OFD1 protein levels in control or PCM1 knockdown (KD) HEK293T cells.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "f, Co-immunoprecipitation of OFD1 with LC3 in control or PCM1 KD HEK293T cells. IP efficiency is calculated as the ratio of immunoprecipitated OFD1/LC3.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "b, Representative confocal images of endogenous OFD1 and acetylated tubulin in Atg5+/+ and Atg5−/− MEFs subjected to 24 hserum starvation. a, b, Data shown represent mean ± s.d. percentage of cells with centriolar satelliteOFD1 for 100 cells per well in triplicate samples. ***P 0.001, two-tailed unpaired student's t-test. Similar results were observed in three independent experiments.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "a, Western blotting analysis of OFD1 protein levels in control or OFD1 knockdown MCF7 (C-19) cells, quantified OFD1 level was normalized with alpha-tubulin.",
    "ncbi_link": "OFD1: 8481"
  },
  {
    "caption": "f, Scanning electron microscope analysis of primary cilia (marked by arrows) formed in C-19 cells subject to 72 h serum starvation and cycling Atg5+/+ MEFs in normal medium for 24 h. Similar results were observed in three independent experiments.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(E-H) Wild-type (E and G) and Atg5−/− (F and H) MEFs were transfected with retroviral vectors encoding GFP-ULK1 and -ULK2. MEFs stably expressing GFP-ULK1 (E and F) and -ULK2 (G and H) were cultured in complete or starvation medium for 120 min. The cells were fixed and examined by fluorescence microscopy. Bars, 20 μm.",
    "ncbi_link": "Atg5: 11793
ULK1: 22241
ULK2: 29869"
  },
  {
    "caption": "(B and C) NIH3T3 cells were transiently transfected with HA-ULK1, HA-ULK2, or their kinase-dead mutants and subjected to immunofluoresence microscopy using monoclonal anti-HA and polyclonal anti-Atg16L1 antibodies for primary staining and Alexa Fluor 488-conjugated goat anti-mouse IgG and Alexa Fluor 568-conjugated goat anti-rabbit IgG antibodies for secondary antibodies. Transfected cells are indicated by arrows. Bars, 20 μm. (D) NIH3T3 cells stably expressing GFP-ULK1K46N and GFP-ULK2K39T were cultured in starvation medium for 120 min. The cells were subjected to immunofluorescence microscopy using anti-Atg16L1 antibody. Bar, 20 μm.",
    "ncbi_link": "ULK1: 22241
ULK2: 29869"
  },
  {
    "caption": "(E) NIH3T3 cells were transfected with the retroviral vectors encoding HA-ULK1K46N or with the corresponding empty retrovirus (mock). They were cultured in complete or starvation medium for 120 min. Cell lysates were then analyzed by immunoblot analysis with the indicated antibodies.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "(A) HEK293T cells were cotransfected with FLAG-FIP200 and HA-ULKs. Cell lysates were subjected to immunoprecipitation (IP) using antibodies against FLAG. The resulting precipitates were examined by immunoblot (IB) analysis with the indicated antibodies. The asterisk indicates nonspecific band.",
    "ncbi_link": "FIP200: 9821"
  },
  {
    "caption": "(B) Lysates of MEFs were immunoprecipitated with anti-ULK1 or anti-FIP200 antibody or preimmune rabbit serum, and the resulting precipitates were subjected to immunoblot analysis with antibodies against ULK1 and FIP200.",
    "ncbi_link": "FIP200: 12421
ULK1: 22241"
  },
  {
    "caption": "(D) HEK293T cells were cotransfected with FLAG-FIP200 and various ULK1 mutants and analyzed as in A using anti-HA and anti-FLAG antibodies.",
    "ncbi_link": "FIP200: 9821"
  },
  {
    "caption": "(E) NIH3T3 cells stably expressing GFP-ULK1 (left) and GFP-ULK1ΔC (right) were cultured in starvation medium for 120 min. Bar, 20 μm.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "(B) NIH3T3 cells stably expressing GFP-FIP200 were cultured in starvation medium for 120 min and then subjected to immunofluorescence microscopy using anti-Atg16L1 antibody and Alexa Fluor 568-conjugated secondary antibody. Bars, 20 μm. More than 90% of GFP-FIP200 dots were positive for Atg16L1.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(A) FIP200+/+, FIP200−/−, Atg5+/+, and Atg5−/− MEFs were cultured in complete or starvation medium for 60 min. In the recovery experiments, starved MEFs were cultured in fresh complete medium for an additional 60 min (replenishment). The cell lysates were subjected to immunoblot analysis with the indicated antibodies.",
    "ncbi_link": "Atg5: 11793
FIP200: 12421"
  },
  {
    "caption": "(B) Wild-type and FIP200−/− MEFs were cultured in the complete or starvation medium for indicated time with or without 100 nM bafilomycin A1. The cell lysates were subjected to immunoblot analysis with anti-LC3 antibody.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(C) Wild-type and FIP200−/− MEFs were transfected with retroviral vectors encoding GFP-Atg5 or GFP-LC3. Resulting cells were cultured in the starvation medium for 120 min. The cells were fixed and examined by fluorescence microscopy. Bar, 20 μm.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(D-G) Wild-type (D and E) and FIP200−/− (F and G) MEFs were cultured in complete (D and F) or starvation (E and G) medium for 120 min and then fixed and subjected to EM analysis. Autophagosome-like structures (open arrowheads), and autolysosomes (closed arrowheads) are indicated. Bar, 1 μm. (H) The ratio of total area of autophagosomes (AP) and autolysosomes (AL) to total cytoplasmic area in D-G was determined by morphometric analysis.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(A) FAK+/− and FAK−/− MEFs were cultured in the complete or starvation medium for the indicated times with or without 100 nM bafilomycin A1. The cell lysates were subjected to immunoblot analysis with the indicated antibodies.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(B) FAK+/− and FAK−/− MEFs stably expressing GFP-LC3 were cultured in complete or starvation medium for 120 min. The cells were fixed and examined by fluorescence microscopy.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(A) Wild-type and FIP200−/− MEFs were treated with 100 ng/ml rapamycin (rapa) or vehicle (DMSO) for 120 min in the presence or absence of 100 nM bafilomycin A1. The cell lysates were subjected to immunoblot analysis with anti-LC3 antibody.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(B) Wild-type and FIP200−/− MEFs stably expressing GFP-Atg5 or GFP-LC3 were cultured in the presence of 100 ng/ml rapamycin for 120 min. The formation of GFP-Atg5 (top) and GFP-LC3 (bottom) puncta was examined by fluorescence microscopy. Bar, 20 μm.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(C) Wild-type and FIP200−/− MEFs were treated with 10 mM lithium chloride for 24 h or 100 μM C2-ceramide for 2 h.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(A) FIP200+/− and FIP200−/− MEFs stably expressing GFP-ULK1 or -ULK2 were cultured in starvation medium for 120 min. The cells were fixed and examined by fluorescence microscopy. Bar, 20 μm.",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(B) FIP200+/+ and FIP200−/− MEFs were cultured in complete medium. The cell lysates were subjected to immunoblot analysis with antibodies against ULK1 or HSP90 (loading control).",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(C) Phosphatase sensitivity of ULK1. FIP200+/+ and FIP200−/− MEFs were cultured in complete medium. ULK1 was immunoprecipitated from cell lysates and treated with λ phosphatase for 30 min at 30°C in the absence or presence of phosphatase inhibitors (1 mM Na2VO4, 50 mM KF, 15 mM Na4P2O7, and 1 mM EGTA).",
    "ncbi_link": "FIP200: 12421"
  },
  {
    "caption": "(D) Change in the expression levels of 17 genes defining anti-cytokine signature; log2 fold change at 24 hours post high SARS-CoV-2 infection from A549-ACE2 cells are shown.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "HEK293 acceptor cells transfected with or without ACE2 and TMPRSS2 were seeded in 384 well plates, pretreated with 7-point gradients of test compounds for 1-2 h, and co-cultured for 4 hours with HEK293 donor cells expressing SARS-CoV-2 spike and GFP, or donor cells expressing GFP only (no spike). Images of GFP-positive objects were acquired on a confocal high-content imager and analyzed for syncytia formation and integrated GFP area (total GFP) as a measure of cytotoxicity, using a CNT algorithm as described in the Materials and Methods. Data are the aggregate of 8 independent biological repeats; where errors are shown they represent SD from matching concentrations in at least three experiments.",
    "ncbi_link": "ACE2: 59272
TMPRSS2: 7113"
  },
  {
    "caption": "(A, B) Overexpression of wildtype full-length human tau (hTau, also termed tau441 or tau40 or tau2N4R) induced significant alterations of 9 transcription factors screened by using Transcription Factors Activation Profiling Plate Array II, in which 96 transcription factors (Appendix Table S1 and S2) were monitored. The empty vector was transfected as a control (Ctrl).",
    "ncbi_link": "hTau: 4137
tau: 4137"
  },
  {
    "caption": "(C-F) Expression of hTau (probed by HT7) increased total and the phosphorylated STAT1 at Tyr701 (pY-STAT1) in cell whole extracts (C, D) and the nuclear fraction (E, F) measured by Western blotting (n=4). Data information: Data were presented as mean ± SD (Mann-Whitney test). *, p<0.05 vs Ctrl.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "(G) The representative immunofluorescent images and quantitative analysis show significantly increased STAT1 signal in the nuclear fraction of HEK293 cells with overexpression of hTau compared with the empty vector control (eGFP) (n=5). Scale bar, 10 μm. Data information: Data were presented as mean ± SD (Mann-Whitney test). , **, p<0.01 vs Ctrl.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "(H) Overexpression of hTau most significantly increased STAT1 monomer and dimer formation in nuclear fraction (Nu) measured by Western blotting.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "(I) Overexpression of hTau increased STAT1 activity in HEK293 cells detected by luciferase assay (n=4). Data information: Data were presented as mean ± SD (Mann-Whitney test). *, p<0.05 , ***, p<0.001 vs Ctrl.",
    "ncbi_link": "hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "(J) Overexpression of hTau increased STAT1-DNA binding activity in HEK293 cells measured by electrophoretic mobility shift assay (EMSA). *, indicates STAT1/DNA complex.",
    "ncbi_link": "hTau: 4137"
  },
  {
    "caption": "(A, B) AAV-hTau-eGFP (AAV-hTau) or the empty vector AAV-eGFP (1.13×1013 v.g./ml) was stereotaxically injected into hippocampal CA3 of 3-month-old C57 mice. After one month, the increased levels of STAT1 and pY-STAT1 in hippocampal total extracts and the nuclear fraction were detected in hTau group by Western blotting (n=6, Mann-Whitney test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "(C, D) The increased STAT1 and pY-STAT1 in hippocampal total extracts and the nuclear fraction of 12-month-old hTau transgenic mice measured by Western blotting (n=4, Mann-Whitney test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "(E, F) The representative images of STAT1 and pY-STAT1 in the brain of AD patients probed by co-immunohistochemical staining and quantitative analysis (hematoxylin stains nuclei, purple; DAB stains the target proteins, brown; n=5-6 slices). Arrowheads indicated typical nuclear staining of STAT1/pY-STAT1. Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "ncbi_link": "eGFP: "
  },
  {
    "caption": "(G) The increased AT8 (pS202/pT205), STAT1 and pY-STAT1 in cortex total extracts of AD patients measured by Western blotting (n=3, Student's t test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "ncbi_link": "eGFP: "
  },
  {
    "caption": "(H) STAT1 mRNA was analyzed by qPCR in AAV-hTau or AAV-eGFP infected hippocampal tissues (n=6, Mann-Whitney test). Data information: Data were presented as mean ± SD. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP, wt or Ctrl.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "AAV-Cre (5×1012 v.g./ml) mixed with AAV-hTau or AAV-eGFP (1.13×1013 v.g./ml) were stereotaxically injected into the hippocampal CA3 of 3-month-old STAT1flox/flox mice. One month later, downregulation of STAT1 was confirmed by immunohistochemical staining.",
    "ncbi_link": "eGFP: 
Cre: 2777477
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "AAV-Cre (5×1012 v.g./ml) mixed with AAV-hTau or AAV-eGFP (1.13×1013 v.g./ml) were stereotaxically injected into the hippocampal CA3 of 3-month-old STAT1flox/flox mice. One month later, downregulation of STAT1 was confirmed by Western blotting",
    "ncbi_link": "eGFP: 
Cre: 2777477
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(C) Downregulation of STAT1 ameliorated hTau-induced spatial learning deficit shown by the decreased escape latency during 5 consecutive days training in Morris water maze (MWM) test (n=9-11 for each group). Data information: Data were presented as mean ± s.e.m. (two-way repeated measures analysis of variance (ANOVA) followed by Bonferroni's post hoc test for C *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP; #, p<0.05, ###, p<0.001 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(D-G) Downregulation of STAT1 ameliorated hTau-induced spatial memory deficit shown by the decreased latency to reach the platform quadrant (D), the increased crossing time in the platform site (E) and time spent in the target quadrant (F) measured at day 6 by removed the platform in MWM test; no motor dysfunction was seen (G) (n=9-11 for each group). Data information: Data were presented as mean ± s.e.m. , one-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test for others). *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP; #, p<0.05, ###, p<0.001 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(H) Downregulation of STAT1 ameliorated hTau-induced contextual memory deficits measured at 24 h during contextual fear conditioning test (n=8 each group). Data information: Data were presented as mean ± s.e.m. *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP; #, p<0.05, ###, p<0.001 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(I-L) One month after the virus infection, paired-pulse ratio (PPR) was recorded in hippocampal CA3 of hTau or STAT1 knockdown mice (I). The IO curve of fEPSP recorded on acute hippocampal slices (J). The slope of fEPSP after HFS recorded on hippocampal slices of hTau or STAT1 knockdown mice (K). LTP magnitude was calculated as the average (normalized to baseline) of the responses recorded 40-60 min after conditioning stimulation. (L). (n=5 slices from 4 mice for each group). Data information: Data were presented as mean ± SD two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test for I-K, one-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test for others). *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP; #, p<0.05, ###, p<0.001 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(M-P) One month after the virus infection, whole cell patch clamp was used to measure the function of NMDA (at +40 mV) and AMPA (at -70 mV) receptors on acute brain slices (400 μm). The insets show representative sample traces of EPSCs in virus infected neurons (M). The reduced NMDA and unchanged AMPA currents with a reduced NMDA/AMPA ratio were seen in hTau infected neurons, while knockdown of STAT1 restored the hTau-induced NMDA currents (N-P). (n=12 neurons from 4 animals for eGFP group; n=11 neurons from 4 animals for hTau group; n=13 neurons from 4 animals for hTau+CRE group). Data information: Data were presented as mean ± SD one-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test for others). *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP; #, p<0.05, ###, p<0.001 vs hTau.",
    "ncbi_link": "eGFP: 
CRE: 2777477
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(A, B) Overexpression of AAV-hTau decreased the protein levels of GluN1, GluN2A and GluN2B detected by Western blotting in the hippocampal CA3 of C57 mice, compared with the AAV-eGFP vector control. (C, D) Simultaneous downregulation of STAT1 by infusing AAV-Cre in hippocampal CA3 of STAT1flox/flox mice abolished the hTau-induced inhibition in expression of NMDARs protein. Data information: Data were presented as mean ± SD (n=4; Mann-Whitney test). *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau.",
    "ncbi_link": "eGFP: 
Cre: 2777477
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(E, F) Overexpression of AAV-hTau or simultaneous downregulation of STAT1 changed the mRNA levels of GluN1, GluN2A and GluN2B detected by qRT-PCR in the hippocampal CA3. Data information: Data were presented as mean ± SD (n=4; Mann-Whitney test). *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau.",
    "ncbi_link": "eGFP: 
GluN1: 14810
GluN2A: 14811
GluN2B: 14812
hTau: 4137
STAT1: 20846"
  },
  {
    "caption": "(A) Overexpression of AAV-hTau increased binding of STAT1 to the promoter regions of GluN1, GluN2A and GluN2B gene in hippocampal CA3 extracts measured by chromatin immunoprecipitation assay (ChIP) (n=3 from three independent experiments). Data information: Data were presented as mean ± SD (two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs Ctrl; ###, p<0.001 vs wildtype reporters.",
    "ncbi_link": "GluN1: 14810
GluN2A: 14811
GluN2B: 14812
hTau: 4137"
  },
  {
    "caption": "(B) Overexpression of hTau or wildtype STAT1 (WT-STAT1) inhibits the transcription activity of NMDARs compared with the empty vector control (Ctrl) measured by luciferase activity assay in HEK293 cells (n=3 from three independent experiments). Data information: Data were presented as mean ± SD (two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs Ctrl; ###, p<0.001 vs wildtype reporters.",
    "ncbi_link": "hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "Diagrams show the predicted GAS promoter element (GASs) for STAT1 in the promoter (-2000-+299bp) of GluN1 (C) The GASs or the mutant (MUT) plasmids were co-transfected respectively with WT-STAT1 or its empty vector (Ctrl) into HEK293 cells for 24 h, and then the luciferase activity was measured (right panels). N=4 for each group. Data information: Data were presented as mean ± SD (two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs Ctrl; ###, p<0.001 vs wildtype reporters.",
    "ncbi_link": "GluN1: 2902
STAT1: 6772"
  },
  {
    "caption": "Diagrams show the predicted GAS promoter element (GASs) for STAT1 in the promoter (-2000-+299bp) of GluN2B (E) The GASs or the mutant (MUT) plasmids were co-transfected respectively with WT-STAT1 or its empty vector (Ctrl) into HEK293 cells for 24 h, and then the luciferase activity was measured (right panels). N=4 for each group. Data information: Data were presented as mean ± SD (two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs Ctrl; ###, p<0.001 vs wildtype reporters.",
    "ncbi_link": "GluN2B: 2904
STAT1: 6772"
  },
  {
    "caption": "Diagrams show the predicted GAS promoter element (GASs) for STAT1 in the promoter (-2000-+299bp) of GluN2A (G, I). The GASs or the mutant (MUT) plasmids were co-transfected respectively with WT-STAT1 or its empty vector (Ctrl) into HEK293 cells for 24 h, and then the luciferase activity was measured (right panels). N=4 for each group. Data information: Data were presented as mean ± SD (two-way analysis of variance (ANOVA) followed by Bonferroni's post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs Ctrl; ###, p<0.001 vs wildtype reporters.",
    "ncbi_link": "GluN2A: 2903
STAT1: 6772"
  },
  {
    "caption": "(A, B) Overexpression of hTau in HEK293 cells for 48 h increased the activity-dependent phosphorylation of JAK2, JNK1 and ERK1 compared with the empty vector control (Ctrl) measured by Western blotting (n=3, student's t test). Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "Pharmacological inhibition of ERK1 (C, D) for 24 h did not significantly affect the hTau-induced STAT1 phosphorylation at pY-STAT1 (Tyr701) in total extracts (C and the nuclear fraction (D measured by Western blotting (n=3). Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "Pharmacological inhibition of JNK1 (E, F) for 24 h did not significantly affect the hTau-induced STAT1 phosphorylation at pY-STAT1 (Tyr701) in total extracts E) and the nuclear fraction F) measured by Western blotting (n=3). The alteration of pS-STAT1 (Ser727) confirms the efficacy of JNK1 inhibitors. Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "Pharmacological inhibition of JAK2 (G, H) abolished hTau-induced STAT1 phosphorylation at Tyr701 in total extracts (G and the nuclear fraction (H (n=3). Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "knockdown JAK2 by siRNA (I, J) abolished hTau-induced STAT1 phosphorylation at Tyr701 in total extracts I) and the nuclear fraction J) (n=3). Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
JAK2: 3717
hTau: 4137"
  },
  {
    "caption": "(K, L) The phosphorylated JAK2 level increased in the hippocampus of 12-month-old hTau transgenic mice (K), and the hippocampus of C57 mice infected with AAV-hTau (1.13×1013 v.g./ml) (L) (n=4, Mann-Whitney test). Data information: Data were presented as mean ± SD, *, p<0.05 vs Ctrl, eGFP or WT.",
    "ncbi_link": "eGFP: 
hTau: 4137"
  },
  {
    "caption": "AAV-eGFP (eGFP) or AAV-hTau-eGFP (hTau) (1.13×1013 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) plus hTau was stereotaxically injected into hippocampal CA3 of 3-month-old C57 mice. After one month, learning and memory were detected by MWM test. (A) The representative fluorescence image confirms expression of AAV-hTau and AAV-Y701F-STAT1. Scale bar, 200 μm, or 100 μm for the enlarged.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "AAV-eGFP (eGFP) or AAV-hTau-eGFP (hTau) (1.13×1013 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) plus hTau was stereotaxically injected into hippocampal CA3 of 3-month-old C57 mice. After one month, learning and memory were detected by MWM test. (B) Overexpression of Y701F-STAT1 mitigated hTau-induced spatial learning deficits shown by the decreased escape latency during water maze training (n=7-10 each group). Data information: Data were presented as mean ± s.e.m (two-way repeated measures analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "AAV-eGFP (eGFP) or AAV-hTau-eGFP (hTau) (1.13×1013 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) plus hTau was stereotaxically injected into hippocampal CA3 of 3-month-old C57 mice. After one month, learning and memory were detected by MWM test. (C-E) Overexpression of Y701F-STAT1 mitigated hTau-induced spatial memory impairment shown by the decreased latency to reach the platform (C), the increased crossing time in the platform site (D) and time spent in the target quadrant (E) measured at day 6 by removed the platform (n=7-10 each group). Data information: Data were presented as mean ± s.e.m , two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "AAV-eGFP (eGFP) or AAV-hTau-eGFP (hTau) (1.13×1013 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) or AAV-Y701F-STAT1 (5×1012 v.g./ml) plus hTau was stereotaxically injected into hippocampal CA3 of 3-month-old C57 mice. After one month, learning and memory were detected by MWM test. (F) Expression of Y701F-STAT1 did not change the swimming speed of the mice in water maze task (n=7-10 each group). Data information: Data were presented as mean ± s.e.m two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "(G-I) Simultaneous expression of Y701F-STAT1 did not induced any further change on basal synaptic transmission (I/O curve) compared with expression of hTau alone, recorded in hippocampal CA3 (G). LTP magnitude was calculated as the average (normalized to baseline) of the responses recorded 40-60 min after conditioning stimulation. (I). (n=5 slices from 4 mice for each group). Data information: Data were presented as mean ± SD , two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "Simultaneous expression of Y701F-STAT1 rescued the hTau-induced suppression of NMDARs protein expression measured by Western blotting in hippocampal CA3 of C57 mice (n=4).",
    "ncbi_link": "hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "Simultaneous expression of Y701F-STAT1 rescued the hTau-induced suppression of NMDARs protein (K) expression measured by Western blotting in hippocampal CA3 of C57 mice (n=4). Data information: Data were presented as mean ± SD two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "Simultaneous expression of Y701F-STAT1 rescued the hTau-induced suppression of NMDARs mRNA expression measured by qRT-PCR in hippocampal CA3 of C57 mice (n=4). Data information: Data were presented as mean ± SD , two-way analysis of variance (ANOVA) followed by Bonferroni' s post hoc test *, p<0.05, **, p<0.01, ***, p<0.001 vs eGFP or hTau; #, p<0.05, ##, p<0.01 vs hTau.",
    "ncbi_link": "eGFP: 
hTau: 4137
STAT1: 6772"
  },
  {
    "caption": "(b) Chromatin immunoprecipitation using α-FLAG antibody was performed to confirm the pull-down of Sα chromatin from the Sα-engineered (FNLDD-Sα-LexA) CH12F3-2A cells. The a, b, and c bars indicate the primers used for ChIP-qPCR as shown in Fig. 1a (n=3; mean + sd; two tailed unpaired Student's t-test).",
    "ncbi_link": "FNLDD: 
LexA: 20466968"
  },
  {
    "caption": "(f) Effect of the siRNA-mediated KD of histone chaperones and chromatin remodelers on IgM to IgA switching in CH12F3-2A cells. Data are presented as the % IgA switching relative to the IgA switching in cells transfected with control siRNA (siCONT) (n=2; mean + sd).",
    "ncbi_link": "IgA: 238447
IgM: 16019"
  },
  {
    "caption": "(a) Top: Scheme of the IgA-switching assay in CH12F3-2A cells. After electroporation of siRNAs, cells were cultured for 24 h, and then stimulated by CIT, cultured for another 24 h, and subjected to FACS analysis. Bottom: Confirmation of the siRNA-mediated KD of SAMHD1 in CH12F3-2A cells.",
    "ncbi_link": "SAMHD1: 56045"
  },
  {
    "caption": "(b) FACS profile of the percentage of CH12F3-2A cells undergoing IgA switching after transfection of the indicated siRNAs into CH12F3-2A cells cultured with (+) or without (-) CIT stimulation for 24 h. The number in the FACS plot represents the percentage of cells expressing IgA on their surface.",
    "ncbi_link": "IgA: 238447"
  },
  {
    "caption": "(c) Summary of the FACS data obtained from three independent experiments. Data are shown as the % IgA switching relative to the IgA switching in cells transfected with control siRNA (siCONT) (n=3; mean + sd; two tailed unpaired Student's t-test).",
    "ncbi_link": "IgA: 238447"
  },
  {
    "caption": "(d) Quantitative RT-PCR analysis of the μGLT, αGLT, Aid, and Samhd1 expression in the indicated samples. The data were normalized to Gapdh, and represents as the mean of the two independent experiments with standard deviations. Statistical significance as determined by two-tailed unpaired Student's t-test is shown. ns = not significant.",
    "ncbi_link": "Gapdh: 
αGLT: 
μGLT: 
Aid: 11628
Samhd1: 56045"
  },
  {
    "caption": "(e) Confirmation of the CRISPR/Cas9 mediated KO of Samhd1 in CH12F3-2A cells. Beta-actin was used as a loading control.",
    "ncbi_link": "Cas9: 
Samhd1: 56045"
  },
  {
    "caption": "(f) CSR time course analysis of WT and Samhd1 KO clones. The data are shown as percentage of IgA expressing cells (n=2; mean ± sd; two tailed unpaired Student's t-test; **, p<0.01).",
    "ncbi_link": "IgA: 238447
Samhd1: 56045"
  },
  {
    "caption": "(g) Proliferation of WT and Samhd1 KO clones after stimulation with CIT (n = 2; mean ± sd; two tailed unpaired Student's t-test; ns = not significant).",
    "ncbi_link": "Samhd1: 56045"
  },
  {
    "caption": "(h) Analysis of the cell proliferation of WT or Samhd1 KO clones of CH12F3-2A. Histograms show the CFSE dye dilution derived from the indicated samples. Aphidicolin (2 μg/mL) was also used as a positive control.",
    "ncbi_link": "Samhd1: 56045"
  },
  {
    "caption": "(i) Schematic representation of the IgG1 or IgG3 switching assay in spleen B cells. Bottom: Western blot analysis of the SAMHD1 expression in spleen B cells derived from WT or Samhd1 KO mice. Tubulin was used as a loading control.",
    "ncbi_link": "IgG1: 16017
IgG3: 380795
Samhd1: 56045"
  },
  {
    "caption": "(j) Bar graphs show the compilation of IgG1 and IgG3 CSR assays from five independent experiments. The data are shown as percentage of IgG1 (left) or IgG3 (right) expressing cells (n=5; mean ± sd; two-tailed unpaired Student's t-test).",
    "ncbi_link": "IgG1: 16017
IgG3: 380795"
  },
  {
    "caption": "(b) Southern blot analysis of PCR-amplified fragments with a Myc-specific probe from two independent experiments. CH12F3-2A cells were transfected with the indicated siRNAs. (c) Frequency of IgH/c-Myc chromosomal translocations derived from two independent experiments (mean ± sd; Fisher's exact test).",
    "ncbi_link": "c-Myc: 
Myc: 
IgH: 111507"
  },
  {
    "caption": "Western blot analysis of the KD of SAMHD1 or TOP1 by the transfection of CH12F3-2A cells by SAMHD1 siRNA or by tetracycline (50 nM) treatment, respectively. Expression of Tubulin is shown as a loading control (e: left). Relative expression of TOP1 and SAMHD1 as determined by densitometric quantification of western blot images in Fig. 3e (e: right).",
    "ncbi_link": "SAMHD1: 56045"
  },
  {
    "caption": "Southern blot analysis of PCR-amplified fragments with a Myc-specific probe from two independent experiments (f). Frequency of IgH/c-Myc chromosomal translocations derived from two independent experiments (mean ± sd; Fisher's exact test) (g).",
    "ncbi_link": "c-Myc: 
Myc: 
IgH: 111507"
  },
  {
    "caption": "(h-j) Analysis of the IgH/c-Myc translocation frequency in WT and Samhd1 KO CH12F3-2A cells. (h) Schematic illustration of the experimental design for the translocation assay. (i) Southern blot analysis of PCR-amplified fragments with a Myc-specific probe from two independent experiments. (j) Frequency of IgH/c-Myc chromosomal translocations derived from two independent experiments (mean ± sd; Fisher's exact test).",
    "ncbi_link": "c-Myc: 
Myc: 
IgH: 111507
Samhd1: 56045"
  },
  {
    "caption": "(k-m) Analysis of the IgH/c-Myc translocation frequency in spleen B cell derived from WT (Samhd1+/+) or Samhd1 KO (Samhd1-/-) mice. (k) Schematic illustration of the experimental design for the translocation assay. (l) Southern blot analysis of PCR-amplified fragments with a Myc-specific probe from two independent experiments. (m) Frequency of IgH/c-Myc chromosomal translocations derived from two independent experiments (mean ± sd; Fisher's exact test).",
    "ncbi_link": "c-Myc: 
Myc: 
IgH: 111507
Samhd1: 56045"
  },
  {
    "caption": "(b) Mutation frequency in the 5′ Sµ region of WT or Samhd1 KO CH12F3-2A cells. Statistical significance as evaluated by Fisher's exact test is shown. ns = not significant.",
    "ncbi_link": "Samhd1: 56045"
  },
  {
    "caption": "(d) LM-PCR analysis of the AID-induced DNA double-strand breaks in the Sµ region of WT or Samhd1 KO CH12F3-2A cells. Wedges indicate a three-fold increase in the DNA amount. Amplification of Gapdh was used as an internal loading control.",
    "ncbi_link": "Gapdh: 
Samhd1: 56045"
  },
  {
    "caption": "(f) Left: Scheme of long-range interactions between Sμ-Sα elements in the IgH locus before and after AID activation. Right: Representative gel picture of the 3C assay detecting the Sμ-Sα interaction in WT or Samhd1 KO CH12F3-2A cells with or without CIT stimulation for 24 h. Gapdh was amplified as a loading control.",
    "ncbi_link": "Gapdh: 
IgH: 111507
Samhd1: 56045"
  },
  {
    "caption": "(a-d) Analysis of Sμ-Sα recombination junctions from WT or CH12F3-2A cells after transfection with control (siCONT) or Ligase 4 (siLIG4) siRNA. The genomic DNA isolated from WT or Samhd1 KO cells from three independent experiments were pooled prior to junction analysis. A total of 62 (siCONT) and 73 (siLIG4) junctions from WT, and 60 (siCONT) and 60 (siLIG4) junctions from Samhd1 KO cells were sequenced and analyzed. Statistical significance as evaluated by Fisher's exact test (b) or two-tailed unpaired Student's t-test (d) or is shown. Schematic representation of the Sμ-Sα junction analysis (a). Summary of the characteristics of Sμ-Sα recombination junctions (b). Sequences at Sμ-Sα recombination junctions with insertions (c). Summary of the average length of insertions at Sμ-Sα recombination junctions (d).",
    "ncbi_link": "LIG4: 319583
Ligase 4: 319583
Samhd1: 56045"
  },
  {
    "caption": "(e-i) Analysis of the CRISPR/Cas9 induced chromosomal translocations between the Rosa26 (Chr6) and H3f3b (Chr 11) genes. The genomic DNA isolated from WT or Samhd1 KO cells from three independent experiments were pooled prior to chromosomal translocation or junction analysis. Schematic representation of the chromosomal translocations (e). Representative images of agarose gels after PCR-amplification of the Rosa26/H3f3b translocation from WT or Samhd1 KO CH12F3-2A cells (f). Relative frequency of Rosa26/H3b3f chromosomal translocations (g). Frequency of junctions containing insertions (h) and average length of insertions (i). Statistical significance as evaluated by two-tailed unpaired Student's t-test (g, i) or Fisher's exact test (h) is shown.",
    "ncbi_link": "Rosa26: 
Cas9: 
H3b3f: 15081
H3f3b: 15081
Samhd1: 56045"
  },
  {
    "caption": "(c) CSR complementation assay in Samhd1 KO cells. Data are shown as the % IgA switching relative to the IgA switching in WT cells transfected with empty vector, and are derived from three independent experiments (mean ± sd; two-tailed unpaired Student's t-test).",
    "ncbi_link": "IgA: 3493
Samhd1: 25939"
  },
  {
    "caption": "(e) Effect of deoxyribonucleoside supplementation individually or in combination on the rate of IgM to IgA switching in CH12F3-2A cells. Data are presented as % IgA switching relative to the IgA switching in cells treated with an equivalent volume of the solvent in which the deoxyribonucleosides were dissolved (n=3; mean ± sd; two-tailed unpaired Student's t-test; ** = p ≤ 0.01; *** = p ≤ 0.001).",
    "ncbi_link": "IgA: 238447
IgM: 16019"
  },
  {
    "caption": "(f) Effect of deoxyribonucleoside supplementation individually or in combination on the frequency of IgH/c-Myc translocations in CH12F3-2A cells (n = 2; mean ± sd; Fisher's exact test; ns = not significant; *** = p ≤ 0.001). The concentration dNTPs used for supplementation either individually or in combination were as follows: 2′-deoxyguanosine (dG), 0.15 mM; 2′-deoxyadenosine (dA), 1.0 mM; 2′-deoxycytidine (dC), 12 mM; and 2′-deoxythymidine (dT), 1.6 mM.",
    "ncbi_link": "c-Myc: 
IgH: 111507"
  },
  {
    "caption": "(b) FACS profile of the percentage of WT and Samhd1 KO CH12F3-2A cells undergoing IgA switching following transfection with the indicated plasmids. The number in the FACS plot represents the percentage of cells expressing IgA on their surface. (c) Summary of the FACS data obtained from two independent experiments. The data are shown as percentage of IgA expressing cells upon CSR induced by blunt (left) or staggered (right) DSBs (n = 2; mean + sd; two-tailed unpaired Student's t-test); ns = not significant.",
    "ncbi_link": "IgA: 238447
Samhd1: 56045"
  },
  {
    "caption": "Analysis of the effect of TdT expression on the frequency of CSR as well as characteristics of Sμ-Sα recombination junctions resulting from the joining of DSBs with blunt ends. (j) Top: Schematic representation of the experimental design to analyze the effect of TdT expression on CSR in WT and Samhd1 KO cells. Bottom: Western blot analysis of the expression of TdT in WT and Samhd1 KO cells. Tubulin was used as a loading control.",
    "ncbi_link": "Samhd1: 56045"
  },
  {
    "caption": "(k) FACS profile of the percentage IgA switching in WT or Samhd1 KO CH12F3-2A cells with or without TdT expression. (l) Summary of the FACS data obtained from two independent experiments (n = 2; mean + sd; two-tailed unpaired Student's t-test; * = p ≤ 0.05).",
    "ncbi_link": "TdT: 21673
IgA: 238447
Samhd1: 56045"
  },
  {
    "caption": "A. Cellular expression and PV incorporation of spike were assessed by Western blotting using an anti-S2 mAb. Lentiviral capsid components were detected using anti-p24/55.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "D. Single  cell morphology assay  of MDA-MB-231  cells cultured in 3D-collagen and analysed for morphology 24 hours after transient knock-down using either a control sequence (NT, non-targeting) or a sequence targeting the RASSF1 locus. RASSF1 knock-down marks a reduction in rounded cells. Data information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.",
    "ncbi_link": "RASSF1: 11186"
  },
  {
    "caption": "C.  Western blot  analysis of proteins in MDA-MB-231 cells transiently transfected with siRNA targeting a control sequence (NT) or targeting RASSF1. GAPDH was used as a loading control.",
    "ncbi_link": "RASSF1: 11186"
  },
  {
    "caption": "D. Immunoprecipitation from MDA-MB-231 transiently transfected with control (pcDNA3) or HA‑RASSF1C plasmid. Pull‑down was performed using a SRC or same species IgG antibody and blotted  with indicated antibodies.",
    "ncbi_link": "HA: 
RASSF1C: 11186"
  },
  {
    "caption": "H. Quantification of rounded  versus elongated cells in single cell morphology assay in 3D‑collagen indicating the degree of mesenchymal-amoeboid transition of MDA-MB-231  cells when RASSF1C  or the described mutants are expressed. I. Representative confocal images show elongated or  rounded  cells per field of view of MDA‑MB-231 cells transfected with DsRed, DsRASSF1C, DsRASSF1C-R197W or DsRASSF1C-R199F, grown in 3D‑collagen and  stained with Phalloidin-568 (red) for  F‑actin and pMLCII/Alexa 633. Scale bars represent 10 μm. ",
    "ncbi_link": "RASSF1C: 11186"
  },
  {
    "caption": "A. Left: Cartoon showing the principle behind the Cre-carrying EVs and how recipient cells switch from DsRed+ to eGFP+ expression upon Cre-mediated excision of the  DsRed  locus. Centre: representative images, and right: quantification of  T47DDsRed cells that converted to  eGFP+ in the bottom wells of a transwell system in the presence of MDA-MB-231CFP;Cre;Control or MDA‑MB‑231CFP;Cre;HA-RASSF1C  seeded in the upper wells. Scale bars represent 100 μm. Data information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, **** p ≤ 0.0001.",
    "ncbi_link": "CFP: 
HA: 
Cre: 2777477
RASSF1C: 11186"
  },
  {
    "caption": "C. Western blot  analysis of EVs isolated from  MDA-MB-231 cells transfected with Control (pcDNA3) or FLAG-RASSF1C with indicated antibodies. Equal amounts of protein were loaded after normalization via microBCA assay.",
    "ncbi_link": "FLAG: 
RASSF1C: 11186"
  },
  {
    "caption": "D. Representative confocal images (upper row) and quantification of fluorescent intensity of  ALDH1 expression in MDA-MB-231  cells expressing RASSF1C (black bar in the graph) or after siRNA treatment against RASSF1  (grey bar). Lower row shows merged images with DAPI  (blue), ALDH1 (green) and RASSF1C (red). Scale bars represent 20 μm. Data Information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.",
    "ncbi_link": "RASSF1: 11186
RASSF1C: 11186"
  },
  {
    "caption": "J. qRT‑PCR expression of NANOG,  OCT4, SOX2 in MCF7 cells 24 h after exposure to 50 ng/μl  EVs derived from MDA‑MB‑231 cells (treated as indicated). Data Information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001. ",
    "ncbi_link": "NANOG: 79923
OCT4: 5460
SOX2: 6657"
  },
  {
    "caption": "B. Left: representative confocal images of mammary tumor formed by the co-injection of T47DDsRed reporter cells with either MDA-MB-231CFP;Cre;Control or MDA-MB-231CFP;Cre;HA-RASSF1C. Scale 200 μm. Right: averaged values for all mice for the percent of the  eGFP+ or CFP+ cells as part of the whole tumor. Data information: All data are from n=3 independent experiments. Data are analyzed by Student T-test and represented as mean ± SEM.* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001.",
    "ncbi_link": "CFP: 
HA: 
Cre: 2777477
RASSF1C: 11186"
  },
  {
    "caption": "B.  Kaplan-Meier  plots of overall  survival of 496 stage I and II breast cancer patients with different levels of promoter/CpG island  methylation of RASSF1A, previously reported to be associated with outcome in breast cancer patients. P values were obtained from a log-rank test.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "C. Left: heatmap depicting methylation  patterns across the RASSF1  gene. In light green, RASSF1-2γ  CpG island is depicted; in dark green, RASSF1-1α CpG island is depicted. Right: Kaplan‑Meyer survival curves  depicting interaction of RASSF1A    and RASSF1C methylation to predict the outcome of early stage breast cancer patients. P values were calculated from a log-rank test. Color legend: yellow, low RASSF1A   and low RASSF1C; green, low RASSF1A  and high RASSF1C; red, high RASSF1A  and low RASSF1C; grey, high RASSF1A and high RASSF1C.",
    "ncbi_link": "RASSF1: 11186
RASSF1A: 11186
RASSF1C: 11186"
  },
  {
    "caption": "Cytokines and innate immune mediators' profile in the brain of mice from different experimental groups: (F) IFN-β1, (G) ISG15, (H) Mx1, detected in one brain hemisphere of mice from different experimental groups. The expression of the genes of interest was normalized to the GAPDH housekeeping gene.",
    "ncbi_link": "GAPDH: 14433
IFN-β1: 15977
ISG15: 100038882
Mx1: 17857"
  },
  {
    "caption": "Cytokines and innate immune mediators' profile in the brain of mice from different experimental groups: , (I) IFN-γ, (J) CXCL10, (K) CCL5, (L) IL-6, (M) TNF-α and (N) IL-1β, detected in one brain hemisphere of mice from different experimental groups. The expression of the genes of interest was normalized to the GAPDH housekeeping gene.",
    "ncbi_link": "CCL5: 20304
CXCL10: 15945
GAPDH: 14433
IFN-γ: 15978
IL-1β: 16176
IL-6: 16193
TNF-α: 21926"
  },
  {
    "caption": "A. Representative FISH images showing RAB13 RNA distribution in MDA-MB-231 cells. Nuclei and cell outlines are shown in blue and green respectively. Arrows points to RAB13 RNA concentrated at protrusive regions. Boxed regions are magnified in the insets.",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "B. Representative immunofluorescence images of RAB13 protein in cells transfected with the indicated siRNAs. Reduction of intensity in RAB13 knockdown cells confirms the specificity of the signal. Arrows point to perinuclear RAB13 protein. Calibration bar shows intensity values. C. Ratios of peripheral/perinuclear intensity calculated from images as shown in A and B. Bars: mean ± s.e.m..Values within each bar represent number of cells observed in 3 independent experiments. ",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "B. FISH images of mouse fibroblasts expressing the β-globin coding sequence followed by the indicated UTRs. β-globin RNA is shown in yellow. Nuclei and cell outlines are shown in blue. Arrows points to β-globin RNA concentrated at protrusive regions. ∆1 and ∆1+2 indicate deletions of the regions shown in (A). Scale bars: 10 μm. C. Distribution of β-globin RNA, or of Ddr2 RNA detected in the same cells, quantified by measuring a Peripheral Distribution Index (PDI). N=35-55 cells observed in 3 independent experiments. Bars: mean ± 95% CI. ****:p<0.0001 by analysis of variance with Dunnett's multiple comparisons test. ",
    "ncbi_link": "Ddr2: 18214
β-globin: 3043"
  },
  {
    "caption": "B. FISH images and corresponding PDI measurements of mouse fibroblast cells treated with the indicated PMOs. Cyb5r3 is an APC-dependent RNA also enriched at protrusions. Arrows: peripheral Rab13 RNA. Arrowheads: perinuclear Rab13 RNA. Boxed regions are magnified in the insets. Note that Rab13 RNA becomes perinuclear in cells treated with PMOs against the GA-rich region. Scale bars: 10 μm. (4 μm in insets). ****: p<0.0001 by analysis of variance with Dunnett's multiple comparisons test. N=40-90 cells observed in 3-6 independent experiments. Bars: mean ± 95% CI.",
    "ncbi_link": "Cyb5r3: 109754
Rab13: 68328"
  },
  {
    "caption": "C. Protrusion (Ps) and cell body (CB) fractions were isolated from cells treated with control-PMO or Rab13-PMO #2. The indicated RNAs were detected through nanoString analysis to calculate Ps/CB enrichment ratios (n=3; bars: mean ± s.e.m.). Note that only the distribution of Rab13 RNA is affected. **: p=0.01 by two-way ANOVA with Bonferroni's multiple comparisons test against the corresponding control. D. Levels of the indicated RNAs were determined using nanoString analysis from control- or Rab13 PMO #2-treated cells. (n=4; bars: mean ± s.e.m.). No significant differences were detected by two-way ANOVA against the corresponding controls. ",
    "ncbi_link": "Rab13: 5872"
  },
  {
    "caption": "A. Schematic showing %GA content and positions along the human RAB13 3'UTR targeted by the indicated PMOs. Red rectangles indicate the location of GA-rich motifs. Graphs present PDI measurements of RAB13 RNA (upper panel) or NET1 RNA (another APC-dependent RNA; bottom panel) detected in MDA-MB-231 cells treated with the indicated PMOs. PDI=1 indicates a diffuse distribution. p-values: **<0.01, ***<0.001, ****<0.0001 by analysis of variance with Dunnett's multiple comparisons test. n.s.: non-significant. N=30-73 cells observed in 3-5 independent experiments. Bars: mean ± s.e.m..",
    "ncbi_link": "NET1: 10276
RAB13: 5872"
  },
  {
    "caption": "B. Representative FISH images of cells treated with the indicated PMOs. Arrows point to peripheral RNA. Arrowheads point to perinuclear RNA. Boxed regions are magnified in the insets. Note that RAB13 RNA becomes perinuclear in cells treated with PMOs against the GA-rich region, while NET1 remains localized at protrusions. Scale bars: 10 μm (4 μm in insets).",
    "ncbi_link": "NET1: 10276
RAB13: 5872"
  },
  {
    "caption": "C. RAB13 protein levels were measured by quantitative Western blot and normalized to total α-Tubulin or GAPDH levels (for representative blot, see Figure 5E). Relative levels in RAB13 PMO-treated compared to control are shown. No significant differences were detected by Kruskal-Wallis test with Dunn's multiple comparisons test. N=3-8. Bars: mean ± SD.",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "A. Transwell migration of MDA-MB-231 cells treated with control PMOs or RAB13 PMOs (191+230). Cells reaching the bottom surface after 4hrs were counted. n=25 fields of view in each of 6 independent experiments. Bars: mean ± s.e.m..",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "B. Cells expressing Cherry-NLS, and treated with the indicated PMOs, were tracked every 5min for 10hrs to derive average migration speed. n=65 cells. Bars: mean ± s.e.m..",
    "ncbi_link": "Cherry-NLS: "
  },
  {
    "caption": "D. Lifeact-GFP-expressing cells were treated with the indicated PMOs and imaged every minute over 1 hr. Sequential image frames, from a control cell, highlight edge retraction (red arrowheads) or protrusion (yellow arrowheads). Corresponding edge velocity is shown, with negative values indicating retraction and positive values indicating extension. Average protrusion and retraction speeds were calculated from n=11-13 cells. Bars: mean ± s.e.m..See also movies EV2 and EV3.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "G. Migration speed of RAB13 knockdown cells re-expressing GFP-RAB13 or GFP-RAB13 with a frameshift (fs) mutation at the beginning of the RAB13 coding region. 28-52 cells were analyzed. Bars: mean ± s.e.m.. Similar results were obtained in two additional independent experiments. Re-expressing cells were identified through GFP fluorescence and cells with similar, low GFP signal were tracked. All cells are expressing cherry-NLS for accurate tracking.",
    "ncbi_link": "cherry-NLS: 
GFP: 
RAB13: 5872
RAB13: 68328"
  },
  {
    "caption": "A. Widefield images of RAB13 immunofluorescence in MDA-MB-231 cells treated with control or RAB13 (191+230) PMOs and ratios of peripheral/perinuclear intensity. Scale bars: 10 μm. n=45-50 cells. Bars: mean ± s.e.m.. Similar results were observed in two additional independent experiments.",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "B. Fluorescence images (projections of confocal slices throughout the cell height) of cells expressing GFP-RAB13 with the indicated UTRs. Note that in both cases the protein assumes indistinguishable distribution. Scale bars: 10 μm.",
    "ncbi_link": "GFP: 
RAB13: 5872"
  },
  {
    "caption": "A. Immunoprecipitation and Western blot analysis to detect proteins bound to GFP-RAB13 expressed from constructs carrying wt or ∆PMO RAB13 3'UTR. GFP-RAB13 (T22N) expresses a nucleotide-free mutant which binds tightly to putative GEFs. RABIF panel is also shown with adjusted contrast to reveal lower binding to wtGFP-RAB13. B. Quantification of RABIF binding to RAB13 from experiments as in (A). n=6. Bars: mean ± s.e.m.. ",
    "ncbi_link": "GFP: 
RAB13: 5872"
  },
  {
    "caption": "C. Active RAB13 pulldown assay from cells with CRISPR knockdown of RABIF using the indicated sgRNAs. n=3. Bars: mean ± s.e.m..",
    "ncbi_link": "CRISPR: 
RABIF: 5877"
  },
  {
    "caption": "F. Representative RABIF-GFP PLA images and quantitations from cells expressing GFP-RAB13(T22N) carrying wt or ∆PMO RAB13 3'UTR. N>70 cells. Bars: mean ± s.e.m.. Arrows indicate PLA signal at the cell periphery. Arrowheads indicate PLA signal within the cell body. Boxed regions are magnified in the insets. Scale bars: 10 μm; 4 μm in insets.",
    "ncbi_link": "GFP: 
RAB13: 5872"
  },
  {
    "caption": "B. Quantification of GFP RNA levels associating with RABIF in immunoprecipitation assays from the indicated cell lines. Note that even though RABIF binds several-fold more to RAB13(T22N) (see Figure 7A, B) it binds similarly to the wild-type and T22N RAB13 RNA, indicating that RABIF binds similarly to nascent RAB13. After translation, it is likely displaced upon GTP-loading of wild type RAB13, while it remains more stably bound to the nucleotide-free (T22N) form. N=6. Bars: mean ± s.e.m.. p-values: *<0.05 by analysis of variance with Dunn's multiple comparisons test.",
    "ncbi_link": "GFP: 
RAB13: 5872"
  },
  {
    "caption": "Analysis of ER architecture and dynamics as a function of RNF26 in U2OS cells ectopically expressing mCherry-KDEL and transfected with either control siRNA (siC) or siRNAs targeting RNF26 (siRNF26-1 or siRNF26-2). B. Time-lapse imaging. Top panels: representative confocal fluorescence images of Cherry-KDEL (white) at the start of time-lapse t=0 (top). Middle panels: time color coded overlays of 60x1s frames, each assigned a different color LUT (white - same ER location across all frames; color - ER movement between frames). Bottom panels: overlays of twice eroded ER sheet masks (magenta) with mCherry-KDEL signal (green). Masks were generated using ImageJ software. Zoom-ins show select PN and PP regions. Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively.",
    "ncbi_link": "mCherry: 
RNF26: 79102"
  },
  {
    "caption": "I. CLIMP63 abundance as a function of RNF26. Top: representative immunoblot of U2OS cells transfected with the indicated siRNAs stained against endogenous CLIMP63 and Vinculin (loading control). Bottom: quantification of CLIMP63 abundance, normalized to Vinculin and expressed relative to control (siC=1.0), n=4 independent experiments. Data information: Graphs report mean or median (red line) of sample values (open circles). Significance was assessed using Student's t-test with error bars reflecting +/- SD)",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "J, K. Effect of RNF26 depletion on basal ER stress using IRE1-mediated XBP1 splicing as a readout. J. Relative abundance of RNF26 transcript normalized to GAPDH; n=3 independent experiments. All transcripts were detected by qPCR. Plots report values relative to control (siC=1.0). K. Quantification of IRE1-dependent XBP1 splicing. XBP-s and XBP1 transcripts isolated from U2OS cells transfected with the indicated siRNAs were detected by qPCR, normalized to GAPDH, and expressed as ratio, n=3 independent experiments. Data information: Graphs report mean or median (red line) of sample values (open circles). Significance was assessed using Student's t-test J and K with error bars reflecting +/- SD) p<0.05; *** p<0.001, ns: not significant.",
    "ncbi_link": "IRE1: 2081
GAPDH: 2597
RNF26: 79102
XBP-s: 7494
XBP1: 7494"
  },
  {
    "caption": "C, D. Proximity biotinylation of endogenous vimentin by 2HA-TurboID-RNF26, catalytically inactive point mutant (I382R), or RING domain truncation mutant (∆RING) in HeLa cells following 30 min incubation with biotin prior to lysis. C. Representative immunoblots of neutravidin precipitates and lysate inputs stained against HA and vimentin. D. Quantifications of vimentin biotinylation by 2HA-TurboID-RNF26 and mutants normalized to auto biotinylated HA-tagged RNF26 species and expressed relative to RNF26 WT, n=6 independent experiments performed in U2OS and HeLa cells. Data information: WCL: whole cell lysate. Graphs in D report mean (red line) and SEM (error bars) of sample values (open circles). Significance was assessed using Student's t-test; * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "HA: 
TurboID: 
RNF26: 79102"
  },
  {
    "caption": "G. Proximity-based biotinylation of endogenous vimentin by 2HA-TurboID-I382R, -∆RING, and -I382R-∆C lacking amino acids 423-433. Immunoblots of neutravidin precipitates and lysate inputs against HA and vimentin are shown and are representative of three independent experiments. Data information: WCL: whole cell lysate.",
    "ncbi_link": "HA: 
TurboID: "
  },
  {
    "caption": "A-E. Analysis of RNF26 sequence determinants with respect to the intracellular distribution of RNF26 and its colocalization with vimentin filaments. A. Representative confocal fluorescence images of U2OS cells ectopically expressing RFP-RNF26 (green) wild-type (WT) or mutants (I382R, ∆RING, ∆C), fixed and immunostained against endogenous vimentin (magenta) and VAP-A (magenta). Indicated single channels and their corresponding color overlays are shown. Zoom-ins highlight PN regions. B. Colocalization (Manders') analysis of RFP-RNF26 and mutants overlap with vimentin. Plot reports n WT=38, n I382R=31, n ΔRING=34, n ΔC=22 cells analysed from three independent experiments. C. Colocalization (Manders') analysis of RFP-RNF26 and mutants with VAP-A. Plot reports n WT=29, n I382R=21, n ΔRING=17, n ΔC=16 cells analysed from three independent experiments. D. Perinuclearity of RFP-RNF26 as a function of its RING domain determinants. Plot reports n WT=72, n I382R=48, n ΔRING=37, n ΔC=28 cells analysed from three independent experiments. E. Intracellular distribution of vimentin as a function of RNF26 (mutant) overexpression. Plot reports n WT59, n I382R=58, n ΔRING=36, n ΔC=32 technical replicates from three independent experiments. Values capped at 10. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm. Statistical analyses were performed using Students' T-test (B, D error bars indicate mean -/+ SD) or Mann-Whitney U test (C, E error bars indicate median and 95% confidence interval); *** p<0.001, ns: not significant.",
    "ncbi_link": "RFP: 
RNF26: 79102"
  },
  {
    "caption": "F, G. Analysis of vimentin cytoskeleton distribution as a function of RNF26. F. Representative confocal fluorescence images of control cells, cells silenced for RNF26 (si#1), or RNF26 KO cells. Zoom-ins highlight PN regions. G. Perinuclearity of vimentin in the presence or absence of RNF26. Plot reports n control=98, n siRNF26=132, n RNF26 KO=41 technical replicates from three independent experiments. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm. Statistical analyses were performed using Students' T-test Mann-Whitney U test error bars indicate median and 95% confidence interval); *** p<0.001, ns: not significant.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "H. Vimentin abundance as a function of RNF26. Top: representative immunoblot of U2OS cells transfected with siRNF26#1 stained against endogenous vimentin and Vinculin (loading control). Bottom: quantification of vimentin abundance, normalized to Vinculin and expressed relative to control (siC=1.0), n=4 independent experiments. Statistical analyses were performed using Students' T-test error bars indicate mean -/+ SD) ; *** p<0.001, ns: not significant.",
    "ncbi_link": "RNF26: 79102"
  },
  {
    "caption": "A-D. Effect of vimentin ablation on intracellular distribution of RNF26. A. Representative confocal images of parental and vimentin knockout (Vim KO) U2OS cells ectopically expressing GFP-RNF26 (green), fixed and immunostained against endogenous VAP-A (magenta). B. Validation of vimentin knockout. Immunoblots against endogenous vimentin and Vinculin (loading control) of a Vim KO clonal cell line and their parental U2OS cells are shown, representative of three independent experiments. Molecular weight markers are as indicated. C. Quantification of GFP-RNF26 signal distribution expressed as perinuclearity ratio. Graph reports n Parental = 73, n Vim KO = 43 technical replicates from three independent experiments. D. Colocalization (Manders') analysis of VAP-A overlapping with GFP-RNF26 (left plot) and vice versa (right plot). Plots report on subset of cells from data set in (B), same as in (C). Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Zoom-ins designate regions encompassing perinuclear and peripheral areas. All scale bars = 10µm. Graphs report mean (red line) of sample values (open circles). Statistical analyses were performed using Students' T-test (D Mann-Whitney U test (C error bars indicate median and 95% confidence interval); * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "E, F. Effect of vimentin or RNF26 ablation on the intracellular distribution of endolysosomes. E. Representative confocal images of parental, RNF26 KO, vimentin KO #1 U2OS cells, vimentin KO#1 cells ectopically complemented with untagged wild type vimentin (Vim KO + Rescue), fixed and immunostained against endogenous LAMP1. F. Quantification of LAMP1 signal distribution expressed as perinuclearity ratio. Graph reports on n Parental = 145, n R26 KO = 64, n Vim KO#1 = 119, n Vim KO#1/Rescue= 32 technical replicates from three independent experiments.Values capped at 6. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Zoom-ins designate regions encompassing perinuclear and peripheral areas. All scale bars = 10µm. Graphs report mean (red line) of sample values (open circles). Mann-Whitney U test F error bars indicate median and 95% confidence interval); * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "R26: 79102
RNF26: 79102
Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "G, H. Effects of vimentin ablation on trafficking of extracellular materials to lysosomes. G. Time-lapse imaging. Representative confocal overlays of parental and vimentin KO#2 U2OS cells, stained with SiR-Lysosome (magenta) to mark late endocytic compartments and incubated with the cell impermeable dye SR101 (green), taken soon after the start (t=5 min) and at the end (t=120 min) of time-lapse are shown. Zoom-ins highlight select PN regions in overlay and single channels. H. Colocalization (Manders') of SiR-Lysosome overlapping SR101 at t=120 minutes following SR101 addition. Graph reports on n Parental = 71, n Vim KO = 69 technical replicates from 3 independent experiments. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Zoom-ins designate regions encompassing perinuclear and peripheral areas. All scale bars = 10µm. Graphs report mean (red line) of sample values (open circles). Statistical analyses were performed using Students' T-test H error bars indicate mean -/+ SD) ; * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "Effect of vimentin ablation on ER organization and dynamics. Analysis of parental versus vimentin KO#1 U2OS cells ectopically expressing mCherry-KDEL. D. Time-lapse imaging. Left panels: representative confocal fluorescence images of Cherry-KDEL (white) at the start of time-lapse t=0 (top). Middle panels: time color coded (TCC) overlays of 60x1s frames. Right panels: overlays of twice eroded ER sheet masks (magenta) with mCherry-KDEL signal (green). Masks were generated using ImageJ software. Zoom-ins show select PN and PP regions. Scale bar = 10µm.",
    "ncbi_link": "mCherry: 
vimentin: 7431"
  },
  {
    "caption": "D, Consequences of RNF26, UBE2J1, and vimentin loss on ERQC formation. D. Representative confocal images of fixed U2OS cells transfected or genetically modified as indicated, treated in the absence (-) or presence (+) of tunicamycin (5ug/mL, O/N), fixed and immunostained against endogenous calnexin (white).",
    "ncbi_link": "RNF26: 79102
UBE2J1: 51465
vimentin: 7431"
  },
  {
    "caption": "F, G. Consequences of RNF26, UBE2J1, and vimentin loss on induction of PERK-mediated UPR signaling by tunicamycin. F. U2OS cells, transfected or genetically modified as indicated, were treated in the absence (-) or presence (+) of tunicamycin (2.5µg/mL, 5hrs). Immunoblots of whole cell lysates against endogenous PERK, phospho-eIF2a, ATF4, HERP1, and Vinculin (loading control) are shown, representative of three independent experiments. G. CHOP transcripts isolated from U2OS cells transfected or genetically modified as indicated and treated in the absence (-) or presence (+) of tunicamycin (2.5ug/mL, O/N) were detected by qPCR and normalized to GAPDH; n siC (-)=4, n siC (+)=4, n siRNF26#1 (+)=3, n siRNF26#2 (+)=4, n PARENTAL (+)=4, n Vim KO (+)=4 independent experiments. Data information: Graphs report mean or median (red line) of sample values (open circles). Statistical analyses were performed using Students' T-test G error bars indicate mean -/+ SEM) p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "CHOP: 1649
PERK: 9451
GAPDH: 2597
RNF26: 79102
UBE2J1: 51465
Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "A, Analysis of localization of RNF26 sequence variants and HERP1 or HERP2 in the ER. A. Representative confocal images of U2OS cells transfected with GFP-RNF26 WT, RFP-RNF26 I382R, GFP-RNF26 ΔRING and HERP1 or GFP-RNF26 WT with HA-HERP2 that were stained for HA and endogenous VAP-A. Indicated single channels and their corresponding color overlays are shown. Zoom-ins highlight PN regions. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm.",
    "ncbi_link": "GFP: 
HA: 
RFP: 
HERP1: 9709
HERP2: 64224
RNF26: 79102"
  },
  {
    "caption": "C. Analysis of determinants for RNF26 complex formation with ERQC proteins HERP1 and HRD1. U2OS cells were transfected with RFP-RNF26 variants (WT, I382R, ΔRING) or EV with either HA-HERP1 or HA-HRD1 before lysis in 1% DMNG detergent, pulldown with RFP-TRAP beads and analysis by SDS-PAGE and WB. Representative images of three independent replicates.",
    "ncbi_link": "HA: 
HRD1: 
RFP: 
HERP1: 9709
RNF26: 79102"
  },
  {
    "caption": "D, E. Analysis of localization of ERQC domains with vimentin. D. Representative confocal images of U2OS cells transfected with HA-HERP1 that were stained for endogenous vimentin. Indicated single channels and their corresponding color overlays are shown. Zoom-ins highlight PN regions where vimentin surrounds HERP1-labeled ERQC domains. E. Line graph analysis of HA-HERP1 (magenta) and vimentin (green) signals from E (bottom zoom image). Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm.",
    "ncbi_link": "HA: 
HERP1: 9709"
  },
  {
    "caption": "F, G. Analysis of HERP1-induced ERQC domain localization as a function of vimentin and RNF26. F. Representative confocal fluorescence images of control cells, RNF26 KO cells, or vimentin KO#2 cells, transfected with HA-HERP1 and immunostained for HA. Zoom-ins highlight PN regions. G. Perinuclearity analysis of HA-HERP1 in the presence or absence of RNF26 or vimentin. Plot reports median (red line) and 95% confidence interval (error bar) of sample values (open circle), n Parental=79, n R26 KO=51, n Vim KO=45 technical replicates from three independent experiments (Mann-Whitney U test; ** p<0.01, *** p<0.001). Graphs report median (red line) and 95% confidence interval (error bars) of sample values (open circles). Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm.",
    "ncbi_link": "HA: 
HERP1: 9709
R26: 79102
RNF26: 79102
Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "C, D. Lysosomal processing of Sec62-HALO-GFP over time in the presence or absence of RNF26 or vimentin. C. Parental, Vim KO#2 or RNF26 KO U2OS cells were transfected with Sec62-HALO-GFP overnight, incubated with 6-chlorohexanol for 15 minutes, washed 3 times with PBS, pulsed with TAMRA HALOtag ligand (200nM) for 1hr, and incubated with 6-chlorohexanol with or without Bafilomycin A1 (100nM) for the indicated times before cell lysis and analysis by SDS-PAGE. Shown is a representative in-gel fluorescence scan with indication of full-length Sec62, protease-resistant HALO fragment and molecular weight markers (MW), as well as a Vinculin blot (loading control) D. Quantification of Sec62 accumulation in LEs from (B). Unprocessed and protease-resistant (lysosomal) band intensities in (B) were calculated with ImageJ and ratios of lysosomal Sec62 versus unprocessed Sec62 were normalized to transfer in parental cells after 10 hours. Error bars show mean +/- SD of n Parental=6, n R26 KO=4, n Vim KO =6 independent experiments. Scale bar = 10µm. Graphs report mean (in D of sample values (open circles). Statistical analyses were performed using Students' T-test (D (paired) ; * p<0.05, ** p<0.01, *** p<0.001).",
    "ncbi_link": "R26: 79102
RNF26: 79102
Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "E, F. Sec62-mediated transfer of ER to lysosomes as a function of RNF26 or vimentin. E. Representative Airyscan images of Parental, RNF26 KO or Vim KO#2 U2OS cells that were transfected with Sec62-HALO-GFP, incubated with 6-chlorohexanol for 15 minutes, washed 3 times with PBS, pulsed with JF646 HALOtag ligand for 1hr, and incubated with 6-chlorohexanol and Bafilomycin A1 for 8hrs before fixation and immunostaining for CD63 to visualize LEs. F. Colocalization (Manders') analysis of CD63 over HALO signals from (D). Plot reports n Parental=106, n R26 KO=69, n Vim KO =68 technical replicates from three independent experiments. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, respectively. Scale bar = 10µm. Graphs report mean (in F) of sample values (open circles). Statistical analyses were performed using Students' T-test F (unpaired) ; * p<0.05, ** p<0.01, *** p<0.001).",
    "ncbi_link": "GFP: 
HALO: 
R26: 79102
RNF26: 79102
Sec62: 7095
Vim: 7431
vimentin: 7431"
  },
  {
    "caption": "G, H. Sec62-mediated transfer of ER to lysosomes as a function of RNF26 overexpression and activity. G. Representative spinning disc live cell images of RNF26 WT and I382R inactive mutant with Sec62. U2OS cells were transfected overnight with Sec62-HALO-GFP and RFP-RNF26 WT or I382R, incubated for 5hrs with JF646 and imaged by spinning disc microscopy. Images show overlay of GFP (green), JF646 (magenta) and RFP signals, zoom-ins of overlay and single channels that show transfer of RNF26 into LEs (WT RNF26). H. Analysis of Sec62 transfer to proteolytic compartments as a function of RNF26 WT or I382R overexpression. Number of GFP-negative/HALO-positive signals was manually counted from cells in (B) and (G). Plot reports n EV=86, n R26 WT=35, n R26 IR =40 technical replicates from three independent experiments. Data information: Cell and nuclear boundaries are demarcated using dashed and continuous lines, median (in H) of sample values (open circles). Mann-Whitney U test (H); * p<0.05, ** p<0.01, *** p<0.001).",
    "ncbi_link": "GFP: 
HALO: 
RFP: 
R26: 79102
RNF26: 79102
Sec62: 7095"
  },
  {
    "caption": "ALP assay. The cells expressing Pho8Δ60p were cultured in SD+CA medium (open bars) and shifted to SD(−N) medium for three hours (filled bars). The ALP activity of the lysates was measured to estimate autophagic activity. Wild-type cells, TN124; Δapg8 mutant harboring vector, TK303; Δapg8 mutant harboring APG8 on a centromeric vector, TK301; Δapg8 mutant harboring 3 × HA-tagged APG8 plasmid, TK307.",
    "ncbi_link": "apg8: 852200
APG8: 852200
Pho8: 852092"
  },
  {
    "caption": "Expression of APG8. A, The lysates prepared from the growing cells were subjected to immunoblotting with the anti-Apg8p antibody. Lane 1, wild-type cells (YW5-1B); lane 2, Δapg8 cells harboring APG8 on a multicopy vector (TK201); lane 3, Δapg8 cells (TK404).",
    "ncbi_link": "apg8: 852200
APG8: 852200"
  },
  {
    "caption": "C, YW5-1B cells were cultured in YEPD medium until 1-2 × 107 cells/ml (0 h) and shifted to SD(−N) medium for 0.5, 1, 2, and 6 h at 30°C, and mRNA was prepared from each culture as described in Materials and Methods. APG8 mRNA and ACT1 mRNA were detected by Northern blotting with each specific probe. Each lane has 4 μg of total mRNA.",
    "ncbi_link": "ACT1: 
APG8: 852200"
  },
  {
    "caption": "Immunofluorescent staining of Δapg8 cells expressing 3 × HA-Apg8p. A, The Δapg8 cells harboring 3 × HA-tagged APG8 plasmid, TK114 cells, were grown until logarithmic phase. The cells were fixed by formaldehyde and were treated with Zymolyase 100T to generate spheroplasts. The spheroplasts were permeabilized by 0.5% Triton X-100, and incubated with the anti-HA antibody, 16B12, followed with the FITC-conjugated anti-mouse IgG. Left, Fluorescence image of 3 × HA-Apg8p; right, Nomarski image of the cells. Arrows show punctate signals that are a little larger than tiny dot signals. Bars, 10 μm. B, Immunofluorescent staining of YW5-1B cells before (0 h) and after (3 h) shift to starvation (negative control). Left, Fluorescence image; right, Nomarski image. Bars, 10 μm. C, The cells were shifted to starvation for 0, 0.5, and 3 h. Upper panels, Fluorescence images of 3 × HA-Apg8p; lower panels, Nomarski images of the cell. Bars, 5 μm.",
    "ncbi_link": "apg8: 852200
APG8: 852200"
  },
  {
    "caption": "Change of Apg8p localization in Δpep4 cells after shift to starvation. The Δapg8Δpep4 cells harboring 3 × HA-tagged APG8 plasmid, TK116 cells, were shifted to starvation for 0, 0.5, 1, 3, and 6 h. Immunofluorescence microscopy was performed as described in Fig. 5. A-E, FITC staining of 3 × HA-Apg8p. F-J, Nomarski images of the cells. Arrows show an autophagic body. Bars, 5 μm.",
    "ncbi_link": "apg8: 852200
APG8: 852200
pep4: 855949"
  },
  {
    "caption": "Immunostaining image of a cell containing autophagic bodies in the vacuole. The Δapg8Δpep4 cells expressing 3 × HA-Apg8p, TK116 cells, were shifted to SD(−N) medium for two hours. Cells were immunolabeled with anti-N mAb, 16B12, followed by 10-nm gold-conjugated goat anti-mouse IgG. AB, vacuole; N, nucleus; V, vacuole.",
    "ncbi_link": "apg8: 852200
pep4: 855949"
  },
  {
    "caption": "Fine morphology of Δypt7 and Δapg8 cells and proteinase-K accession to proAPI in these mutants. A, EM image of Δypt7 cell starved in SD(−N) medium for four hours. Autophagosomes (AP, arrows) were accumulated. B, EM image of the starved Δapg8 cell. C-E, The representatives of the membrane structures detected in the starved Δapg8 cells. C, Autophagosome-like structure indistinguishable from autophagosome. D and E, Aberrant multivesicular structures. N, nucleus; V, vacuole. F, Proteinase K-sensitivity of proAPI. Cell lysates were prepared from Δypt7 and Δapg8 cells starved in SD(−N) medium for 4.5 h. The lysates were treated with 100 μg/ml proteinase K in the presence or absence of Triton X-100. Asterisk shows mature API and digestion product of proAPI by proteinase K.",
    "ncbi_link": "apg8: 852200
ypt7: 855012"
  },
  {
    "caption": "Colorectal tumor outcomes in WT (n=7), IL-33KO (n=4) and ST2KO (n=3) mice at the completion of the AOM/DSS carcinogenesis protocol. (A) Tumor volumes at the endpoint (each dot represents a tumor, mice with no tumor are marked as zero), Skin tumor outcomes in WT (n=7), IL-33KO (n=6) and ST2KO (n=7) mice at the completion of the DMBA/DNFB carcinogenesis protocol. (D) Tumor volumes at the endpoint (each dot represents a tumor, mice with no tumor are marked as zero),",
    "ncbi_link": "IL-33: 77125
ST2: 17083"
  },
  {
    "caption": "H) Quantification of nuclear IL-33+ epidermal and dermal cells in the DNFB- versus acetone-treated WT skin. Dots represent cell counts from three randomly selected high power field (HPF) images per sample (n=5 per group). J) Quantification of nuclear IL-33+ epithelial and stromal cells of colon treated with AOM/DSS versus no treatment. Dots represent cell counts from three randomly selected HPF images per sample (n=4 per group). Data information: Graphs show mean + SD, unpaired t-test. ",
    "ncbi_link": "IL-33: 77125"
  },
  {
    "caption": "(H) ChIP-qPCR assay for Smad6 in the presence of IL-33 full length or cytokine domain using an anti-RUNX2 antibody. After Pam212 cells were transfected with IL-33 full length or cytokine domain for 24 hours, cell lysates were subjected to chromatin-immunoprecipitation with anti-RUNX2 antibody and eluted RUNX2-bound chromatin was used for qPCR with primers against Smad6 promoter region. Anti-IgG ChIP-qPCR results are shown as negative controls (n=4 per group).",
    "ncbi_link": "IL-33: 77125
Smad6: 17130"
  },
  {
    "caption": "(D) Immunoblot of p-SMAD2/3 and SMAD2/3 proteins in response to TGF-β and poly (I:C) treatment. Pam212 cells were treated with poly (I:C) or PBS followed by incubation with and without TGF-β (5nM). Data represent three independent experiments with similar results. (E) Immunoblot of p-SMAD2/3 and SMAD2/3 proteins in response to TGF-β + poly (I:C) after knocking down of IL-33. Pam212 cells were transfected with siIl33 knockdown construct or siRNA control (siCon) for 30 hours followed by incubation with poly (I:C) and TGF-β. Data represent three independent experiments with similar results. (F) Immunoblot of p-SMAD2/3 and SMAD2/3 proteins upon the expression of IL-33 full length or cytokine domain. Pam212 cells were transfected with IL-33 full length or cytokine domain for 24 hours followed by incubation with and without TGF-β. Data represent three independent experiments with similar results. Data information: GAPDH is used as the control housekeeping protein in D-F). Graphs show mean + SD, NS: not significant, unpaired t-test.",
    "ncbi_link": "IL-33: 77125
siIl33: 77125"
  },
  {
    "caption": "(G) Impact of IL-33 knockdown on cell proliferation in response to TGF-β. Pam212 cells were treated with siIl33 or siCon followed by TGF-β treatment (n=7 in each group). (H) Impact of IL-33 knockdown and SB431542 treatment on cell proliferation. Pam212 cells were treated with siIl33 or siCon in combination with SB431542 or DMSO (carrier control, n=7 in each group). ",
    "ncbi_link": "IL-33: 77125
siIl33: 77125"
  },
  {
    "caption": "(I) SMAD signaling proteins levels in WT and K14-IL33tg,ST2KO skin treated with acetone (control) at the completion of the DMBA/TPA carcinogenesis protocol. Tissue lysates prepared from the whole back skin of the animals were subjected to immunoblot with p-SMAD2/3, p-SMAD1/5, SMAD6, SMAD2/3 and SMAD1 antibodies. GAPDH is used as the control housekeeping protein (n=5 in each group).",
    "ncbi_link": "IL33: 77125
K14: 3861
ST2: 17083"
  },
  {
    "caption": "(B) Il33 and Smad6 mRNA levels in caerulein-treated WT pancreas compared with PBS-treated controls at the completion of chronic pancreatitis protocol (n=8 in caerulein and n=9 in PBS group for Il33, n=9 in caerulein and n=10 in PBS group for Smad6, unpaired t-test).",
    "ncbi_link": "Il33: 77125
Smad6: 17130"
  },
  {
    "caption": "(D) Pancreatic tumor-free survival of WT (n=4), IL-33KO (n=5) and ST2KO (n=6) mice at the completion of the DMBA/caerulein carcinogenesis protocol (log-rank test).",
    "ncbi_link": "IL-33: 77125
ST2: 17083"
  },
  {
    "caption": "B Mitochondrial transcript levels measured by qRT-PCR in RKO cells after 96 hours of 1 μM  IMT1 treatment. Data are relative to  DMSO-treated controls and are expressed as mean ± SD of n=4 independent experiments. Ordinary one-way ANOVA was used for comparisons to DMSO-treated controls (RNR1, RNR2,  MT-COX2, MT-ATP6, MT-ND1: ***p<0,0001).",
    "ncbi_link": "MT-ATP6: 4508
MT-COX2: 4513
MT-ND1: 4535
RNR1: 6052
RNR2: 4550"
  },
  {
    "caption": "G Relative mtDNA copy number measured in RKO and  IMT1-resistant cells treated with  IMT1  for 96 hours. Data are expressed as average from n=3 experiments ± SEM. Statistical significance was calculated with one-way ANOVA test.  RKO + IMT1 vs Resistant + IMT1: MT-ND1 **p=0,0035, MT-ATP6 ***p=0,0002, MT-CYTB **p=0,0028.",
    "ncbi_link": "MT-ATP6: 4508
MT-CYTB: 4519
MT-ND1: 4535"
  },
  {
    "caption": "G Viable cells counts of IMT1-resistant RKO cells treated for one-week with either DMSO or IMT1 in presence of controls (control #1, #2) or TFAM (TFAM  #1, TFAM #2) siRNAs. Data are expressed as mean values ± SD of n=5 independent experiments each including six technical intra-plate replicates. Statistical significance was calculated with one-way ANOVA test. Controls + IMT1 vs TFAM #1 + IMT1: p= 0,2148; Controls + IMT1  vs TFAM #2 + IMT1: *p=0,0415.",
    "ncbi_link": "TFAM: 7019"
  },
  {
    "caption": "293T cells were transfected with a plasmid encoding FLAG-Stx17 wild type (WT) or the indicated constructs. At 24 h after transfection, cell lysates were immunoprecipitated (IP) with anti-FLAG M2 beads, and analyzed by IB using antibodies against PGAM5 and FLAG. Five percent of lysates was analyzed as input.",
    "ncbi_link": "FLAG: 
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing FLAG-Stx17 WT or the K254C mutant were fixed and subjected to PLA using antibodies against FLAG and PGAM5. Scale bar, 5 μm. Values are means ± SEM (n = 3). ***P<0.001 as compared with WT (paired Student's t-test).",
    "ncbi_link": "FLAG: 
Stx17: 55014"
  },
  {
    "caption": "MBP or the MBP-Stx17 constructs attached to amylose resin were mixed with GST-PGAM5, and the proteins bound to the resin were separated by SDS-PAGE and blotted onto PVDF membranes. The blots were detected by an anti-GST antibody (upper panels) or stained with Coomassie Brilliant Blue R-250 (lower panels). Ten percent of the proteins used for each experiment was analyzed as input. Asterisks and double asterisk may represent MBP dimers and degradation products.",
    "ncbi_link": "GST: 
MBP: 
PGAM5: 192111
Stx17: 55014"
  },
  {
    "caption": "293T cells were cotransfected with plasmids encoding FLAG-Stx17 WT and the indicated PGAM5-GFP constructs, and analyzed",
    "ncbi_link": "FLAG: 
GFP: 
PGAM5: 192111
Stx17: 55014"
  },
  {
    "caption": "293T cells were cotransfected with plasmids encoding FLAG-Stx17 or Stx18 and the C-terminally GFP-tagged transmembrane domain of PGAM5（amino acids 1-35）constructs, and analyzed",
    "ncbi_link": "FLAG: 
GFP: 
Stx18: 
PGAM5: 192111
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing FLAG-Stx17 wild type (WT) were transfected with a plasmid encoding Su9-GFP (mitochondria) or Sec61β-GFP (ER). At 24 h after transfection, the cells were subjected to PLA using antibodies against FLAG and PGAM5. Scale bar, 5 μm. The bar graph on the right shows the Manders' coefficients for the colocalization of PLA dots and Su9-GFP or Sec61β-GFP. Values are means ± SEM (n = 3). ***P<0.001 (paired Student's t-test).",
    "ncbi_link": "FLAG: 
GFP: 
Sec61β: 
Su9: 
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing FLAG-Stx17 WT were mock-transfected or transfected with siRNA for Mfn1, Mfn2 or PACS-2. At 72 h after transfection, the cells were subjected to PLA using antibodies against FLAG and PGAM5. Scale bar, 5 μm. Values are means ± SEM (n = 3). ***P<0.001 as compared with Mock (paired Student's t-test).",
    "ncbi_link": "FLAG: 
Mfn1: 55669
Mfn2: 9927
PACS-2: 23241
Stx17: 55014"
  },
  {
    "caption": "HeLa cells were mock-transfected or transfected with siRNA for Mfn1, Stx17, Mfn2 or PACS-2. At 72 h after transfection, the cells were subjected to PLA using antibodies against Drp1 and PGAM5. Scale bar, 5 μm. Values are means ± SEM (n = 3). ***P<0.001 as compared with Mock (paired Student's t-test).",
    "ncbi_link": "Mfn1: 55669
Mfn2: 9927
PACS-2: 23241
Stx17: 55014"
  },
  {
    "caption": "HeLa cells with mock treatment (Mock) or depleted of Stx17 (Stx17 KD) were fixed and double immunostained for PGAM5 and Tom20. Scale bar, 5 μm.",
    "ncbi_link": "Stx17: 55014"
  },
  {
    "caption": "293T cells with mock treatment or depleted of Stx17 were incubated with ethanol (Vehicle) or 20 μM CCCP (+CCCP) for 2 h, lysed and then analyzed by IB using the indicated antibodies.",
    "ncbi_link": "Stx17: 55014"
  },
  {
    "caption": "293T cells transiently expressing FLAG-Stx17 wild type (WT) or the K254C mutant were incubated with ethanol (Vehicle) or 20 μM CCCP (+CCCP) for 2 h, lysed, immunoprecipitated with anti-FLAG M2 beads and then analyzed by IB using the indicated antibodies.",
    "ncbi_link": "FLAG: 
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing FLAG-Stx17 WT were incubated with ethanol (Vehicle) or 20 μM CCCP (+CCCP) for 2 h, and subjected to PLA using antibodies against FLAG and PGAM5. Scale bar, 5 μm. Values are means ± SEM (n = 3). ***P<0.001 as compared with Vehicle (paired Student's t-test).",
    "ncbi_link": "FLAG: 
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing GFP-Parkin with mock treatment (Control) or depleted (KD) of Stx17, PGAM5 or Drp1 were incubated for 16 h with ethanol (Vehicle) or 10 μM CCCP (+CCCP), and analyzed by IB using the indicated antibodies.",
    "ncbi_link": "GFP: 
Drp1: 10059
PGAM5: 192111
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing GFP-Parkin with mock treatment (Mock) or depleted of Stx17, PGAM5 or Drp1 were incubated in the absence (Vehicle) or presence of 20 μM CCCP (+CCCP) for 2 h and analyzed by immunofluorescence microscopy. Scale bar, 5 μm. The bar graph on the right shows the Manders' coefficients for the colocalization of GFP-Parkin and Tom20. Values are means ± SEM (n = 3). ***P<0.001 as compared with Mock (paired Student's t-test).",
    "ncbi_link": "GFP: 
Drp1: 10059
PGAM5: 192111
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "PINK1-FLAG and GFP-Parkin stably expressing HeLa cells with mock treatment or depleted of Stx17 or PGAM5 were incubated in the absence (ethanol) or presence of 20 μM CCCP for 2 h and analyzed by IB using the indicated antibodies. F, full-length PINK1; C, cleaved PINK1.",
    "ncbi_link": "FLAG: 
GFP: 
PGAM5: 192111
PINK1: 65018
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "GFP-Parkin stably expressing HeLa cells were mock-transfected (Mock) or transfected with siRNA (KD) for Stx17 or PGAM5. At 48 h after siRNA transfection, the cells were transfected with a plasmid encoding FLAG-DFCP1, incubated for 24 h, treated with 20 μM CCCP for 2 h and then immunostained for FLAG. Scale bars, 5 μm. The bar graph below shows the Manders' coefficients for the colocalization of GFP-Parkin and FLAG-DFCP1. Values are means ± SEM (n = 3). **P<0.01 as compared with Mock (paired Student's t-test).",
    "ncbi_link": "DFCP1: 
FLAG: 
GFP: 
PGAM5: 192111
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "GFP-Parkin stably expressing HeLa cells with mock treatment or depleted of Stx17 or PGAM5 were incubated with 20 μM CCCP for 2 h and immunostained for LC3. Scale bar, 5 μm. The bar graph below shows the Manders' coefficients for the colocalization of GFP-Parkin and LC3. Values are means ± SEM (n = 3). **P<0.01 as compared with Mock (paired Student's t-test).",
    "ncbi_link": "GFP: 
PGAM5: 192111
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "GFP-Parkin stably expressing HeLa cells with mock treatment or depleted of Stx17 or PGAM5 were incubated in the absence (Vehicle) or presence of 20 μM CCCP (+CCCP) for 2 h and analyzed by IB using the indicated antibodies.",
    "ncbi_link": "GFP: 
PGAM5: 192111
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "HeLa cells stably expressing GFP-Parkin with mock treatment (Control) or depleted of FUNDC1 (FUNDC1 KD) were incubated for 16 h with ethanol (Vehicle) or 10 μM CCCP (+CCCP), and analyzed by IB using the indicated antibodies.",
    "ncbi_link": "GFP: 
FUNDC1: 139341
Parkin: 5071"
  },
  {
    "caption": "GFP-Parkin stably expressing HeLa cells with mock treatment (Mock) or depleted of FUNDC1 (FUNDC1 KD) were incubated with 20 μM CCCP for 2 h and immunostained for Tom20. Scale bar, 5 μm.",
    "ncbi_link": "GFP: 
FUNDC1: 139341
Parkin: 5071"
  },
  {
    "caption": "293T cells with mock treatment (Mock) or depleted of Stx17 (Stx17 KD) were incubated in the absence (Vehicle) or presence of 20 μM CCCP (+CCCP) for 2 h, immunoprecipitated with anti-FLAG M2 beads and then analyzed by IB using the indicated antibodies. Three percent of lysates was analyzed as input. During Stx17 knockdown, cells were transfected with a plasmid encoding FLAG-FUNDC1.",
    "ncbi_link": "FLAG: 
FUNDC1: 139341
Stx17: 55014"
  },
  {
    "caption": "GFP-Parkin stably expressing HeLa cells were treated and then subjected to PLA using antibodies against FLAG and PGAM5. During Stx17 knockdown, cells were transfected with a plasmid encoding FLAG-FUNDC1. Scale bar, 5 μm. Values are means ± SEM (n = 3). *P<0.05 and **P<0.01 as compared with Mock (+CCCP) by paired Student's t-test.",
    "ncbi_link": "FLAG: 
GFP: 
FUNDC1: 139341
Parkin: 5071
Stx17: 55014"
  },
  {
    "caption": "A PGAM5 overexpression partially rescues the mitochondrial defects by Stx17 loss. Transmission electron microscope images of the indirect flight muscle in the indicated genotypes (a, Control; b, Stx17-/-; c, Stx17-/- and Stx17 overexpression; d, Stx17-/- and PGAM5 overexpression) of 7-day-old adult flies are shown. The bar graph on the right shows frequency of healthy and abnormal mitochondria presented as percentages (mean ± SEM) using the scoring system : Class 0, normal; Class 1, fuzzy or dilated cristae; Class 2, fragmented cristae and loss of electron density. *p < 0.05, #p < 0.001 vs. the same class of control (Dunnett's test). n = 50-119 mitochondria from three or four independent samples. Genotypes used were: +/y; Act5c-GAL4/+ (a), +/y; Act5c-GAL4/+; Stx17LL06330/Stx17LL06330 (b), +/y; Act5c-GAL4/UAS-FLAG-Stx17; Stx17LL06330/Stx17LL06330 (c), +/y; Act5c-GAL4/UAS-PGAM5; Stx17LL06330/Stx17LL06330 (d). Scale bars, 200 nm.",
    "ncbi_link": "FLAG: 
Act5c: 31521
GAL4: 855828
PGAM5: 31143
Stx17: 38541"
  },
  {
    "caption": "B Simultaneous reduction of Stx17 and PGAM5 results in mitochondrial degeneration. a, Stx17+/-; b, PGAM5-/-; c, Stx17+/-, PGAM5-/-. The bar graph on the right represents the mitochondrial phenotypes classified p < 0.05, **p < 0.01 vs. the same class of Stx17+/- (Dunnett's test). n = 62-195 mitochondria from three independent samples. Scale bars = 1 µm. Genotypes used were: +/y; Act5c-GAL4/+; Stx17LL06330/+ (a), PGAM51/y; Act5c-GAL4/+ (b), PGAM51/y; Act5c-GAL4/UAS-Stx17-FLAG; Stx17LL06330/+ (c).",
    "ncbi_link": "FLAG: 
Act5c: 31521
GAL4: 855828
PGAM5: 31143
Stx17: 38541"
  },
  {
    "caption": "B. Left, representative images of Western blot for ARID1A expression in lysates extracted from the cortex of Arid1afl/+(WT), cHet, and cKO mice using the indicated antibodies. Right, quantification of protein levels normalized to β-actin (n = 3 mice per group).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "C. Left, representative images of Western blot for ARID1A expression in lysates extracted from the hippocampi of Arid1afl/+, cHet, and cKO mice. Right, quantification of protein levels which were normalized to β-actin (n = 4 mice per group).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "D. Immunostaining against ARID1A (red) in the dentate gyrus (DG), cortex, CA1, and CA3 regions of Arid1afl/+and cHet mice.",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "E. cHet mice spent more time reaching the platform during 5-day training in Morris water maze assay compared to the control group mice. Arid1afl/+ (n = 15 mice), cHet (n = 13 mice).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "F. In the probe trial, cHet mice displayed spatial learning disabilities compared with Arid1afl/+ mice. Arid1afl/+ (n = 15 mice), cHet (n = 13 mice).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "G. cHet mice undertook fewer platform crossings than Arid1afl/+ mice in the Morris water maze assay. Arid1afl/+ (n = 15 mice), cHet (n = 13 mice).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "H-J. cHet mice were evaluated using the Barnes maze test. During the training phase, the cHet mice (n = 12 mice) failed to diminish the latency of the first entrance to the hiding box (H), indicating that Arid1a haploinsufficiency results in impaired spatial memory. Probe trials demonstrated that cHet mice also had spatial memory deficits (I), as they visited the target hole less often than the Arid1afl/+ mice (n = 12 mice) (J).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "A. Representative traces of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in CA1 hippocampal acute slices from Arid1afl/+ and cHet mice. B. Quantification of amplitude (B, left) and frequency (B, right) spontaneous miniature excitatory postsynaptic currents (mEPSCs) in Arid1afl/+ and cHet hippocampal CA1 neurons. Arid1afl/+ (17 neurons from n =3 mice) and cHet (15 neurons from n = 4 mice).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "C. Representative recording of the paired-pulse ratio at the 50-ms interpulse interval ms from slices prepared from Arid1afl/+ (n = 4) and cHet (n = 4) mice. D. Paired-pulse facilitation (PPF) studies across different interpulse intervals (20 ms, 40 ms, 50 ms, 100 ms, 200 ms, 300ms, and 500 ms) revealed a significant difference in paired-pulse ratios at 50-ms intervals.",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "E. Summary plots showing the time course of long-term potentiation (LTP) induced by frequency stimulation in the CA1 region from Arid1afl/+or cHet mice. Field excitatory postsynaptic potential (fEPSP) traces before (black) and after (black or red) are shown in the inset above. F. Average amplitude of LTP measured at 55-60 min postinduction (n = 8 slices from 4 mice per group; 10 fEPSP slope (%) values were collected from 1 slice).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "G. Representative Western blot images for the expression of several LTP-related proteins in the Arid1afl/+ and cHet hippocampi. H. Quantification of the expression of each protein normalized to the β-actin level.",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "A. Golgi-stained coronal section in the hippocampal CA1 region of 2-month-old Arid1afl/+ and cHet mice. Scale bar, 100µm. B-D. Partial loss of Arid1a significantly decreased dendritic length (B), dendritic nodes (C), and dendritic ends (D) in cHet neurons. E",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "A. Left, Western blot analysis of H3K27ac in forebrain tissues of Arid1afl/+and cHet mice. Right, relative quantitation of the intensity of H3K27ac normalized to the H3 level (n=3 mice per group).",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "D. Immunofluorescence (IF) staining of H3K27ac(green) and Vgult1(red) in forebrain tissues of Arid1afl/+ and cHet mice, respectively. IF staining was performed on 40-μm thick floating sections. Relative fluorescence intensities of H3K27ac decreased upon the haploinsufficiency of Arid1a in the cortex. Scale Bar, 20μm. Arid1afl/+ (n = 7) and cHet (n = 4) mice.",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "F-H. Morris water maze test of Arid1afl/+ and cHet mice treated with vehicle or acetate. Acquisition task, the latency to find the platform was used to assess learning ability. Latency to the platform was measured during training trials (F). Latency to the platform was measured during probe test (G). (H) Retention task, the times in the target crossings were used to assess memory retention. The times in the target crossings were measured in probe tests, n = 10-15 mice per group.",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "I-K. Barnes maze test of Arid1afl/+ and cHet mice treated with vehicle or acetate. (I) During the training phase, the time to find the target in Arid1afl/+ and cHet mice that were treated with vehicle or acetate for 28 days. (J) In probe test trials, the time of latency to the platform to find the target in Arid1afl/+ and cHet mice treated with vehicle or acetate. (K) In probe trials, the numbers of target crossings of Arid1afl/+ and cHet mice treated with vehicle or acetate (n = 12 mice)",
    "ncbi_link": "Arid1a: 93760"
  },
  {
    "caption": "A. Representative image of vehicle- and acetate-treated neurons derived from WT or ARID1A KO hESCs on day 40 of neural differentiation Scale Bar, 20μm B. Quantification of total neurite length of hESC-derived neurons after treatment with acetate or vehicle. n = at least 34 neurons for each group from 3 independent experiments. C",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "D. Representative images of dendrites (MAP2, green) showing localization of foci of the pre- and postsynaptic protein complexes, synaptophysin (red), and PSD-95 (white) protein in control, acetate treatment of WT and ARID1A KO hESC-derived neurons on day 55 of neural differentiation. Scale Bar, 5μm.",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "(C) day 20±2 cerebral organoids derived from controls, patients and  EML1-heKOs stained  for the  neuronal marker  MAPT and the adherens junction marker  NCAD, counterstained  with  DAPI. Ectopic   neural rosettes and neuronal  heterotopia  are highlighted with dotted yellow lines. (D) Quantification of VZ areas with ectopic neural rosettes (3 batches, 3  organoids analyzed per batch, significance based on Kruskal-Wallis-test, P=0.0001, Dunn's post hoc test for multiple comparisons performed to define statistical differences between genotypes, single data points are presented colored by batch). (E) Quantification of heterotopic, disorganized  or organized cortical areas (3 batches, 3 organoids per batch, significance based on Kruskal-Wallis-test, P=0.0001 for \"organized\" and \"heterotopic\"; no significant difference for \"disorganized\", Dunn's post hoc test performed for multiple comparisons to define statistical differences between genotypes). Data information: * marks statistical significance in relation to Control 1, # in relation to Control 2. P-values: ***/###<0.001. VZ:  ventricular zone; Data in graphs are represented as means ± SD. Scale bars: 50µm.",
    "ncbi_link": "EML1: 2009"
  },
  {
    "caption": "(A) Hybrid   organoids  generated from controls mixed with control-EGFP+ or EML1-heKO-EGFP+ cells (day 20±2). Yellow dotted lines indicate  VZ  areas. (B) Quantification of control-EGFP+ or  EML1-heKO-EGFP+ cells within or at the basal side of VZ  areas (3 batches, 3 organoids  each, significance based on Mann Whitney test, ***P= 0.0001 for \"EGFP+ cells at the  basal side of  VZ  areas\"). Data information: Data in graphs are represented as means ± SD. Scale bars: (A) 50µm",
    "ncbi_link": "EGFP: 
EML1: 2009"
  },
  {
    "caption": "(C) Representative images and scheme of cleavage plan orientation. Upper panel: cells immunostained for pVim (red) and  TPX2 (green), counterstained with DAPI, white dotted line indicates cleavage plane orientation, yellow dotted line VZ-surface. (D) Quantification of horizontal, vertical and  oblique plane of cell divisions in control and  EML1-deficient   organoids   (day 20±2; 3 batches, 3 organoids each). Data information: Scale bars: 5µm",
    "ncbi_link": "EML1: 2009"
  },
  {
    "caption": "(F)  Electron microscopy  of  primary cilia derived from control or EML1-deficient  cortical progenitors  in DMSO-control or following EpothiloneD (EpoD) exposure (blue arrow: basal body, yellow arrow: appendages, red arrow:  ciliary pockets). Data information: Scale bars: 0,5µm.",
    "ncbi_link": "EML1: 2009"
  },
  {
    "caption": "(E) Control and EML1-heKO-derived cerebral organoid stained  for COL1A2  and MEIS2. VZ  areas are encircled, squares indicate areas enlarged in F. (F) Control and EML1-heKO-derived cerebral organoid stained for COL1A2, MEIS2  and MAPT. (G) Representative images showing EGFP-control and EGFP-EML1-heKO hybrid cerebral organoid stained  for EGFP, FAM107A  and NCAD. Yellow dotted lines indicate  morphology of EGFP+ cells (4 independent batches each, 3 organoids  per batch, at least 30 ectopic  rosettes in total). Data information: Scale bars: (E) 50µm; (F) 10µm; (G) 50µm, enlarged 10µm.",
    "ncbi_link": "EGFP: 
EML1: 2009"
  },
  {
    "caption": "(D, E) Immunofluorescence staining for (D) p-VIM and  YAP1  or (E) Pax6 and  YAP1 in control and EML1-heKO-derived  organoids (day 20±2, squares indicate areas enlarged in adjacent part of the panel respectively). (F) Quantification of basally located pVim+ cells with  nuclear YAP1  signal per VZ  area in control and EML1-heKO-derived  organoids (3 batches, 3 organoids  analyzed per batch). (G) Quantification of PAX6+ cells with nuclear YAP1 signal per VZ  area in control and EML1-heKO-derived organoids (3 batches, 3 organoids analyzed per batch). Data information: Data in graphs are represented as means ± SD. Significance based on Kruskal-Wallis-test Dunn's post hoc test for multiple comparisons were performed to define statistical differences between genotypes. P-values: ***<0.001, **<0.01, *<0.05. Scale bars: (D and E) 50µm, enlarged 10µm",
    "ncbi_link": "EML1: 2009"
  },
  {
    "caption": "(H) Immunofluorescence staining for p-Vim  in EML1-heKO and control derived  organoids in DMSO,  Verteporfin  or Fluvastatin treated conditions, counterstained with DAPI. Dotted line indicates VZ  areas. (I) Quantification of p-VIM+ cells located at the basal side  of  VZ  areas in control or EML1-heKO-derived organoids under DMSO, Verteporfin or Fluvastatin treated condition (3 batches, 3 organoids  analyzed per batch). Data information: Data in graphs are represented as means ± SD. Significance based on two-way ANOVA (on log10 normalized data) Tukey post hoc test for multiple comparisons were performed to define statistical differences between genotypes. P-values: ***<0.001, **<0.01, *<0.05. Scale bars: (H) 50µm",
    "ncbi_link": "EML1: 2009"
  },
  {
    "caption": "A The expression  of LINC00839   in CRC  tissues and normal mucosa  tissues in the UALCAN database. B, C, D The expression  of LINC00839  in unpaired CRC  and normal samples in the LnCAR database (GSE37364, GSE71187, and GSE33113). Data information: In A, B, C, D middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "E, F The expression  levels of LINC00839  in tumour tissues and NATs from the CRC  cohort (n = 45). nmCRC denotes CRC patients without metastases, and mCRC denotes CRC patients  with metastases. Data information: In E, F, the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "G Representative ISH staining  of LINC00839  in paraffin-embedded samples of CRC  tumour tissues and NATs. (a) Expression  of LINC00839  in tumour tissues and NATs. Scale bars, 100 μm. (b) Magnification of normal mucosal  area and (c) magnification of the tumour area. Scale bars, 50 μm. (d) Weakly positive staining  of LINC00839  in normal mucosa. Scale bars, 50 μm. (e) Strong positive staining  of LINC00839  in tumours and (f) magnification of the local area. Scale bars, 100 μm.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "I Differential expression  of LINC00839  in nonmetastatic CRC patients  (nmCRC) and metastatic CRC patients  (mCRC). Data information: In I, the data are shown as the mean ± SD and were analysed by Student's t test. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "J Expression  of LINC00839  in CRC patients  with early-stage (stage I  and II) and advanced-stage (stage III  and IV) disease. Data information: In J, middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "C Colony formation assay was performed with LINC00839-overexpressing cells and vector control cells. , the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 biological replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "D Wound-healing assay was performed with LINC00839-overexpressing cells and vector control cells. Scale bars, 100 μm. , the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 biological replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "E Matrigel invasion assay was performed with LINC00839-overexpressing cells. Scale bars, 100 μm. , the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 biological replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "F The CDX model showing the effect of LINC00839  on tumour growth. Representative image of tumours harvested from the mouse  model (upper panel), the quantitative analysis of  tumour weight and tumour volume (medium panel), and representative images and quantification of IHC staining  of Ki-67 in tumours (bottom panel) (n = 6 for each cohort, and the results are presented as the mean ± SD, Student's t test (medium left and low right panel) and ANOVA (medium right). Scale bars, 100 μm (n = 6 biological replicates . Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": ". G The CRC  orthotopic mouse  model revealed the effect of LINC00839  on tumour development. Representative images of primary tumours (yellow arrowheads) and liver metastasis  (blue arrowheads) in the model (upper panel), analysis of tumour volume and the number of mice  with liver metastasis   (medium panel), and H&E staining  of tumours and metastases  (n = 6 for each cohort). Scale bars, 100 μm (n = 6 biological replicates . Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "A An  RNA pull-down assay was performed to identify proteins that bind  to LINC00839  in HCT116  cells.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "B RNA pull-down assay  and WB  showed that biotinylated LINC00839  can bind  to Ruvb1  in HCT116  cells. Dot blot  of RNA-protein interactions indicating equal amounts of RNA used in the assay.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "C RIP  experiments were performed to confirm the binding  of LINC00839  to Ruvb1. IgG was used as a negative control antibody. Primers specific for U6  and GAPDH  were used as negative control primers. Data information: In C, the data are presented as the mean ± SD and were analysed by unpaired t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "GAPDH: 2597
LINC00839: 84856
U6: 26827"
  },
  {
    "caption": "D Different fragments of LINC00839  (solid line) and its antisense sequence (dotted line) were used for the RNA pull-down assay  and the subsequent WB.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "E Full length LINC00839, antisense sequence of LINC00839, and LINC00839  sequence lacking nucleotides 1033-1290 were used for the RNA pull-down assay  and the subsequent WB.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "G The effect of LINC00839  on the expression of Tip60  and Ruvb1  was determined by WB.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "I The interaction  between Ruvb1  and Tip60  in cells overexpressing wild-type LINC00839  and LINC-Δ5 was confirmed by Co-IP.",
    "ncbi_link": "LINC: 84856
LINC00839: 84856"
  },
  {
    "caption": "J The interaction  between Ruvb1 and Tip60  in LINC00839-KD cells and cells expressing LINC-Δ5 was confirmed by Co-IP.",
    "ncbi_link": "LINC: 84856
LINC00839: 84856"
  },
  {
    "caption": "K Acetylase activity assays were performed with LINC00839-overexpressing and LINC00839-knockdown cells. Data information: In the data are presented as the mean ± SD and were analysed by unpaired t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "D, E The ATP  levels and the NAD/NADH   ratio were measured in LINC00839-overexpressing and LINC00839-KD cells (mean ± SD, Student's t test, n = 3 biological replicates). Data information: Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "F Expression of MT-ND5, MT-CYB, MT-CO1, and TFAM  in LINC00839-overexpressing and LINC00839-KD cells as determined by WB.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "G Analysis of NRF1 expression  in CRC  tissues (T) and normal tissues (N) the GEPIA database. Data information: In G, the middle lines represent the median, and the upper and lower lines represent the upper and lower quartiles; the data were analysed by ANOVA. Across experiments, the P values are as follows: ns = not significant, *P < 0.05",
    "ncbi_link": "NRF1: 4899"
  },
  {
    "caption": "H Correlation analysis of LINC00839  and NRF1  mRNA levels in the TCGA and GTEx databases (Pearson).",
    "ncbi_link": "LINC00839: 84856
NRF1: 4899"
  },
  {
    "caption": "I, Expression of NRF1  in LINC00839-overexpressin and LINC00839-KD cells was measured by qPCR  Data information: In I, the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856
NRF1: 4899"
  },
  {
    "caption": "J Expression of NRF1  in LINC00839-overexpressin and LINC00839-KD cells was measured by WB.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "K, L The enrichment of the NRF1  promoter (P1-P10) by H4K5ac and H4K8ac antibodies in LINC00839-overexpressing and control LoVo  cells as determined by CHIP  assay. Normal IgG was used as a negative control. Data information: In K, L, , the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856
NRF1: 4899"
  },
  {
    "caption": "O The enrichment of NRF1  with a probe targeting LINC00839  relative to a NC probe in HCT116  cells, as determined by ChIRP assay. LacZ  served as a negative control (NC). Data information: In O, the data are presented as the mean ± SD and were analysed by Student's t test, n = 3 technical replicates. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LacZ: 945006
LINC00839: 84856
NRF1: 4899"
  },
  {
    "caption": "F ISH staining  of LINC00839  and IHC staining  of NRF1, H4K5ac, and H4K8ac in paraffin-embedded samples of CRC  tumour tissues and NATs. Scale bars, 200 μm.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "G, H, Correlation analysis of the expression  of LINC00839     and NRF1  (G), H4K5ac (H) in CRC patients   (n = 120). Data information: In G, H show the Pearson correlation coefficient results. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "I Correlation analysis of the expression    of LINC00839   and H4K8ac (I) in CRC patients  (n = 120). Data information: In I show the Pearson correlation coefficient results. Across experiments, the P values are as follows: ns = not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.",
    "ncbi_link": "LINC00839: 84856"
  },
  {
    "caption": "(A) μCT analysis of the femurs of 10-week-old male mice upon exposure to low oxygen concentration (14% pO2, n = 5) or ambient air (n = 7), and of 10-week-old Hif1aRank-/-; Hif2aRank-/- male mice upon exposure to low oxygen concentration (14% pO2, n = 6) or ambient air (n = 5) for 10 days (axial view of the metaphyseal region). Scale, 0.5 mm. (B) Histological analysis of the proximal tibias of 10-week-old male mice upon exposure to low oxygen concentration (14% pO2) or ambient air for 10 days, and of 10-week-old Hif1aRank-/-; Hif2aRank-/- male mice upon exposure to low oxygen concentration (14% pO2 ) or ambient air (toluidine blue staining [arrow, osteoclasts]). Scale, 100 μm. (C) Parameters for osteoclasts and osteoblasts during bone morphometric analysis of 10-week-old male mice under low oxygen concentration (n = 3) or ambient air (n = 5), and 10-week-old Hif1aRank-/-; Hif2aRank-/- male under low oxygen concentration (n = 3) or ambient air (n = 5) for 10 days.",
    "ncbi_link": "Hif2a: 13819
Hif1a: 15251"
  },
  {
    "caption": "(A) Protein expression of HIF-1α, HIF-2α, Blimp1, NFATc1, Ctsk and TRAP in control and Hif1aRank-/-; Hif2aRank-/- BMMs stimulated with RANKL and cultured under different conditions of oxygen concentration for 2 days.",
    "ncbi_link": "Hif2a: 13819
Hif1a: 15251"
  },
  {
    "caption": "(B) Effect of physioxia (5% pO2) or physiological hypoxia (2% pO2) on the formation of osteoclast from control and Hif1aRank-/-; Hif2aRank-/- BMMs. TRAP-stained cells (left panel) and the number of TRAP-positive cells with more than three nuclei (right). Scale bar, 100 μm.",
    "ncbi_link": "Hif2a: 13819
Hif1a: 15251"
  },
  {
    "caption": "(C) Expression of osteoclastogenic and canonical HIF-target genes in wild-type control and Hif1aRank-/-; Hif2aRank-/- BMMs under conditions of 5% or 2% oxygen.",
    "ncbi_link": "Hif2a: 13819
Hif1a: 15251"
  },
  {
    "caption": "(A) Representative intravital image of calvarial bone marrow of Rosa26GO-ATeam/+; Tg(Acp5-tdTomato) male mice showing osteoclasts (left, tdTomato fluorescence) and FLIM image for ATP changes (middle and right, fluorescence lifetime of EGFP). The FRET efficiencies of each osteoclast were plotted from the mice upon exposure to low oxygen atmosphere (14% pO2) or ambient air (right, n = 11 from three mice for each SpO2).",
    "ncbi_link": "tdTomato: 
Acp5: 11433
Rosa26: 14910"
  },
  {
    "caption": "(B) Representative intravital image of calvarial bone marrow of Tg(Acp5-tdTomato) male mice showing osteoclasts (left, tdTomato fluorescence) and NAD(P)H autofluorescence lifetime images (middle and right). Average of autofluorescence lifetime of each osteoclast was plotted from the mice upon exposure to low oxygen concentration (14% pO2) or ambient air (right, n = 64 from three mice for each SpO2).",
    "ncbi_link": "tdTomato: 
Acp5: 11433"
  },
  {
    "caption": "(B) μCT analysis of the femurs of 10-week-old control (n = 6), Tet2Rank-/- (n = 5), Tet3Rank-/- (n = 5), Tet2Rank-/-; Tet3aRank+/- (n = 6), Tet2Rank+/-; Tet3aRank-/- (n = 6) and Tet2Rank-/-; Tet3aRank-/- (n = 4) male mice (axial view of the metaphyseal region). (C) Histological analysis of the proximal tibias of 10-week-old control, Tet2Rank-/-, Tet3Rank-/-, Tet2Rank-/-; Tet3aRank+/-, Tet2Rank+/-; Tet3aRank-/- and Tet2Rank-/-; Tet3aRank-/- male mice (TRAP staining [red, osteoclasts]).",
    "ncbi_link": "Tet2: 214133
Tet3: 194388
Tet3a: 194388
Rank: 21934"
  },
  {
    "caption": "(E) Effect of Tet2 and Tet3 double deficiency on osteoclastogenesis. TRAP-stained cells (left panel) and the number of TRAP-positive cells with more than three nuclei (right). (n = 6 (control), n = 10 (Tet2Rank-/-; Tet3aRank+/-), n = 3 (Tet2Rank+/-; Tet3aRank-/-) and n = 4 (Tet2Rank-/-; Tet3aRank-/-) biological replicates",
    "ncbi_link": "Tet2: 214133
Tet3: 194388
Tet3a: 194388
Rank: 21934"
  },
  {
    "caption": "(B) MeDIP-qPCR analysis to validate regions that are hypermethylated in Tet2Rank-/-; Tet3aRank+/- BMMs stimulated with RANKL for 2 days. (C) Gene expression of TET target candidates in BMMs stimulated with RANKL for 2 days.",
    "ncbi_link": "Tet2: 214133
Tet3a: 194388"
  },
  {
    "caption": "(E) Bisulfate sequencing analysis of selected region of the second intron of the Prdm1 gene in control and Tet2Rank-/-; Tet3aRank+/- BMMs stimulated with RANKL for 2 days. (F) Effect of retroviral NFATc1 expression on osteoclastogenesis of control and Tet2Rank-/-; Tet3aRank+/- BMMs stimulated with RANKL for 3 days. TRAP-stained cells (left panel) and the number of TRAP-positive cells with more than three nuclei (right). (G) Bisulfate sequencing analysis of the selected region of the second intron of the Prdm1 gene in BMMs stimulated with RANKL and culture under 5% and 2% oxygen for 3 days. (H) Effect of retroviral NFATc1 expression on osteoclastogenesis of BMMs stimulated with RANKL and culture under 5% and 2% oxygen for 5 days. Control and Tet2Rank-/-; Tet3aRank+/- BMMs stimulated with RANKL for 3 days. TRAP-stained cells (left panel) and the number of TRAP-positive cells with more than three nuclei (right).",
    "ncbi_link": "NFATc1: 18018
Prdm1: 12142
Tet2: 214133
Tet3a: 194388
Rank: 21934"
  },
  {
    "caption": "I Kinetic block of Synaptophysin-pHluorin endocytosis  at hippocampal synapses depleted of VPS34. Hippocampal neurons  depleted of endogenous VPS34 by specific shRNA (shVPS34) or treated with non-targeting control shRNA (shCtrl) and stimulated as in C and analyzed as in D. N =3 independent experiments (≥ 10 images per condition); Two-way ANOVA; Sidak's Multiple Comparison Test. Data information: Data presented as mean ± SEM n.s. not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001;",
    "ncbi_link": "VPS34: 225326"
  },
  {
    "caption": "D Overexpression of dominant-negative Rab5 (Rab5DN), but not constitutively active Rab5 (Rab5CA), rescues the progressive accumulation of Synaptophysin-pHluorin on the surface of VPS34IN1-treated hippocampal neurons stimulated and analyzed as in A-C. N = 3 independent experiments (≥ 10 images per condition); Two-way ANOVA; Tukey's Multiple Comparison Test. Data information: Data presented as mean ± SEM n.s. not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001",
    "ncbi_link": "Rab5: 19345///19344///271457"
  },
  {
    "caption": "F-H Calpain inhibition by  ALLN (100 µM) in F or Calpain 2 knockdown via  lentiviral shRNA (shCAPN2) in H rescue the progressive accumulation of Synaptophysin-pHluorin on the neuronal surface induced by VPS34IN1. Calpain 1 knockdown via lentiviral shRNA (shCAPN1) in G had no impact on VPS34IN1-induced kinetic delay of SV endocytosis. N = 3 independent experiments (≥ 11 images per condition); Two-way ANOVA; Tukey's Multiple Comparison Test. Data information: Data presented as mean ± SEM ; n.s. not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001",
    "ncbi_link": "Calpain 1: 12333
CAPN1: 12333
Calpain 2: 12334
CAPN2: 12334"
  },
  {
    "caption": "PS decarboxylase activity in wild-type (WT, W303) and the indicated mutant strains expressed as (B) the molecular species composition of 13C315N-labeled PS (*PS) and 13C215N-labeled PE (*PE), after 20 min incubation with 13C315N-serine.",
    "ncbi_link": "PS decarboxylase: 855552"
  },
  {
    "caption": "PS decarboxylase activity in a psd1Δpsd2Δdpl1Δ mutant expressing Psd1, Psd1(ER) or Psd1(Mt) expressed as (B) the molecular species composition of *PS and *PE after 20 min incubation with 13C315N-serine",
    "ncbi_link": "dpl1: 851888
psd1: 855552
PS decarboxylase: 855552
Psd1: 855552
psd2: 853080"
  },
  {
    "caption": "PS decarboxylase activity in a psd1Δpsd2Δdpl1Δ mutant expressing Psd1, Psd1(ER) or Psd1(Mt) expressed as ; (C) the corresponding molecular signatures of PSD activity.",
    "ncbi_link": "dpl1: 851888
PS decarboxylase: 855552
psd1: 855552
Psd1: 855552
psd2: 853080"
  },
  {
    "caption": "(B) Acyl chain composition of WT and psd1∆ cells overexpressing SCT1 (pSCT1) vs. empty vector control (pEmpty). Data is presented as mean ± SD (n>10). **** p < 0.0001, multiple t-test.",
    "ncbi_link": "psd1: 855552
SCT1: 852271"
  },
  {
    "caption": "(C) Ratio of the proportions of saturated over unsaturated acyl chains (SFA/UFA) of WT, psd1∆, crd1∆ and psd2∆ overexpressing SCT1 vs. empty vector control. Data is presented as mean ± SD (n≥3). ** p<0.01, **** p < 0.0001, unpaired two-tailed t-test.",
    "ncbi_link": "crd1: 851413
psd1: 855552
psd2: 853080
SCT1: 852271"
  },
  {
    "caption": "(D) OLE1 transcript levels in WT and psd1∆ transformed with pSCT1 vs. pEmpty as determined by RT-qPCR. Data were normalized to endogenous ACT1 mRNA, and to the average of WT pEmpty (n=3).",
    "ncbi_link": "ACT1: 850504
OLE1: 852825
psd1: 855552
SCT1: 852271"
  },
  {
    "caption": "(A) SFA/UFA ratios of WT and indicated mutant strains overexpressing SCT1 (pSCT1) vs. control (pEmpty). Data is presented as mean ± SD (n≥3). * p < 0.05, ** p < 0.01, **** p < 0.0001, n.s. not significant, unpaired two-tailed t-test of the indicated bar compared to WT pSCT1.",
    "ncbi_link": "SCT1: 852271"
  },
  {
    "caption": "(B) Growth of WT and indicated mutant strains overexpressing SCT1 (pSCT1) vs. pEmpty. Serial dilutions (10-1 - 10-4) were spotted on SGal + 0.05% glucose and incubated for 3 days at 30°C.",
    "ncbi_link": "SCT1: 852271"
  },
  {
    "caption": "SFA/UFA-ratio of WT and indicated mutant strains overexpressing SCT1 cultured without (data taken from Fig 5A) and with 1 mM ethanolamine (etn) or 1 mM choline (cho) as indicated. Data is presented as average ± SD (n≥3). * p < 0.05, ** p < 0.01, *** p < 0.001, unpaired t-test of the indicated bar compared to the corresponding condition of WT. Underlying data for this figure can be found in Appendix Table S1.",
    "ncbi_link": "SCT1: 852271"
  },
  {
    "caption": "A Electron microscopy analyses to see autophagic bodies in the vacuoles under both growth and nitrogen starvation conditions. Autophagic bodies typically contain cytosolic ribosomes. pep4∆prb1∆ and pep4∆prb1∆atg2∆ cells were grown in SD to mid‐log phase (OD600 = 1) and transferred to SD(‐N) for 5 h. The cells were examined by transmission electron microscopy as described in . Scale bar, 500 nm.",
    "ncbi_link": "atg2: 855479
pep4: 855949
prb1: 856649"
  },
  {
    "caption": "B-D Time‐dependent changes in nucleoside contents under nitrogen starvation (B), rapamycin treatment (C), and carbon starvation (D) conditions. Wild‐type and atg2Δ cells were grown in SD and transferred to SD(‐N), SD medium with 0.2 μM rapamycin, or SD(‐C) at time 0. At the indicated time points, nucleosides were analyzed by LC/MS as described in . Results are presented as normalized intensities on the basis of peak height of each metabolite in wild‐type cells. All data are means of triplicate samples. The error bars represent the standard deviation.",
    "ncbi_link": "atg2: 855479"
  },
  {
    "caption": "A Time‐dependent changes in nucleoside contents under nitrogen starvation. Nucleosides in wild‐type, atg2Δ, atg7Δ, atg11Δ, atg17Δ, atg19Δ, atg32Δ, nvj1Δ, and pep4prb1Δ cells under nitrogen starvation. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg11: 856162
atg17: 851142
atg19: 854072
atg2: 855479
atg32: 854660
atg7: 856576
nvj1: 856602
pep4: 855949
prb1: 856649"
  },
  {
    "caption": "B Alkaline phosphatase (ALP) assay (Pho8∆60). Wild‐type, atg2∆, atg11Δ, atg17Δ, and atg19Δ cells expressing Pho8∆60 were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, lysates were prepared and subjected to the ALP assay. The bars represent the standard deviation of three independent experiments. *P 0.05; **P 0.005; ***P 0.0005 (paired t‐test, two‐tailed)",
    "ncbi_link": "atg11: 856162
atg17: 851142
atg19: 854072
atg2: 855479"
  },
  {
    "caption": "A-C Wild‐type, atg2Δ, pho8Δ, and rny1Δ cells were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, nucleosides (A) were analyzed by LC/MS as described in . The results are presented as normalized intensities on the basis of the peak height of each metabolite in wild‐type cells. Note that 3′‐NMPs in pho8Δ are presented in a different scale. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg2: 855479
pho8: 852092
rny1: 855980"
  },
  {
    "caption": "A-C Wild‐type, atg2Δ, pho8Δ, and rny1Δ cells were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, 5′‐NMPs (B) were analyzed by LC/MS as described in . The results are presented as normalized intensities on the basis of the peak height of each metabolite in wild‐type cells. Note that 3′‐NMPs in pho8Δ are presented in a different scale. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg2: 855479
pho8: 852092
rny1: 855980"
  },
  {
    "caption": "A-C Wild‐type, atg2Δ, pho8Δ, and rny1Δ cells were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, 3′‐NMPs (C) were analyzed by LC/MS as described in . The results are presented as normalized intensities on the basis of the peak height of each metabolite in wild‐type cells. Note that 3′‐NMPs in pho8Δ are presented in a different scale. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg2: 855479
pho8: 852092
rny1: 855980"
  },
  {
    "caption": "A, B Expression and localization of Rny1 and Pho8. Wild‐type cells and atg2Δ cells expressing Rny1‐GFP or Pho8‐GFP were grown in SD to mid‐log phase and transferred to SD(‐N). After 2 h of starvation, GFP‐tagged proteins were observed by fluorescence microscopy (A). Scale bar, 5 μm.",
    "ncbi_link": "atg2: 855479"
  },
  {
    "caption": "A, B Expression and localization of Rny1 and Pho8. Wild‐type cells and atg2∆ cells expressing Rny1‐GFP or Pho8‐GFP were grown in SD to mid‐log phase and transferred to SD(‐N). After 2 h of starvation, GFP‐tagged proteins were analyzed by Western blot with anti‐GFP antibody (B).",
    "ncbi_link": "atg2: 855479"
  },
  {
    "caption": "C Detection of free RNA. Wild‐type, atg2∆, rny1∆, and rny1∆atg2∆ cells grown in SD (left) or SD(‐N) for 2 h (right) were stained with FM4‐64 and GR Green and observed by fluorescence microscopy. Scale bar, 5 μm.",
    "ncbi_link": "atg2: 855479
rny1: 855980"
  },
  {
    "caption": "A Time‐dependent change in nucleoside levels after nitrogen starvation. Wild‐type, atg2∆, ubp3∆, and bre5∆ cells were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. Metabolites were analyzed by LC/MS as described in . The results are presented as normalized intensities on the basis of the peak height of each metabolite in wild‐type cells. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg2: 855479
bre5: 855787
ubp3: 856895"
  },
  {
    "caption": "B Detection of free RNA within cells. rny1∆, rny1∆atg2∆, rny1∆ubp3∆, and rny1∆bre5∆ cells grown in SD(‐N) for 2 h were stained with FM4‐64 and GR Green and observed by fluorescence microscopy. Scale bar, 5 μm.",
    "ncbi_link": "atg2: 855479
bre5: 855787
rny1: 855980
ubp3: 856895"
  },
  {
    "caption": "B, C Nucleosides (B) and nucleobases (C) within the cells. Wild‐type and atg2∆ were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, the cells were collected; their metabolites were extracted, and the nucleosides and nucleobases were analyzed by LC/MS. The level of each nucleoside and base is presented as its absolute concentration, as described in and Supplementary Methods. All data are means of duplicates except the wild‐type strain at 1 h.",
    "ncbi_link": "atg2: 855479"
  },
  {
    "caption": "Wild‐type and atg1Δ of S. pombe were grown in SD to mid‐log phase and transferred to SD(‐N) at time 0. At the indicated time points, the cells were collected; the metabolites in these cells were extracted and analyzed by LC/MS as described in . The results are presented as normalized intensities on the basis of peak height of each metabolite in wild‐type cells. All data are means of triplicates. The error bars represent the standard deviation.",
    "ncbi_link": "atg1: 2539461"
  },
  {
    "caption": "(A) Tru-Seq RNA sequence analysis of E12.5 midbrain floor-plate (mFP), midbrain roof-plate (mRP), anterior (A, adjacent anterior FP) and posterior (P, adjacent posterior FP). Pbx1 is enriched in the midbrain FP, together with Th and Pitx3. Lower levels of Pbx3 are also expressed in the mFP. Gdf7 and Wnt1 are restricted to the mRP at E12.5.",
    "ncbi_link": "Gdf7: 238057
Pbx1: 18514
Pbx3: 18516
Pitx3: 18742
Th: 21823
Wnt1: 22408"
  },
  {
    "caption": "(B) Pbx1 is expressed in the intermediate zone (IZ) and marginal zones (MZ), but not the ventricular zone (VZ), of the mFP at E12.5, as detected by in situ hybridization.",
    "ncbi_link": "Pbx1: 18514"
  },
  {
    "caption": "(A) To the left, representative immunofluorescence microscopy/confocal images showing that the number of TH+cells is reduced in Pbx1-/- embryos. Deletion of Pbx1 decreases the proportion of NURR1+neuroblasts that become TH+neurons at E12.5, indicating that Pbx1 is required for the proper maturation of NURR1+neuroblasts. To the right, quantification of these experiments.",
    "ncbi_link": "Pbx1: 18514"
  },
  {
    "caption": "(B) Ectopic PBX3 is detected in all rostro-caudal levels of the VM in Pbx1-/- mice at E12.5, indicating a repressive function of PBX1 on Pbx3 expression.",
    "ncbi_link": "Pbx1: 18514"
  },
  {
    "caption": "(C) Representative immunofluorescence microscopy/confocal images and quantification showing that the conditional deletion of Pbx1 and Pbx3 (cKO, Pbx1flox/flox;Pbx3-/-;Th-IRES-Cre-ERT) reduces the number of PITX3+cells in rostral VM levels, but not of NURR1+cells, when compared to double heterozygous at E14.5 (cHET, Pbx1flox/+;Pbx3-/+;Th-IRES-Cre-ERT). White boxes are magnified to the right.",
    "ncbi_link": "Cre: 
ERT: 13983///13982
Pbx1: 18514
Pbx3: 18516
Th: 21823"
  },
  {
    "caption": "(B) Representative immunofluorescence microscopy/confocalimages showing that PBX1-overexpression increases the number of TH+neurons after 8 days of differentiation of hNES cells (AF22 line derived from induced pluripotent stem cells). (C) While the number of cells (Dapi+) in both conditions did not change, the number of TH+cells increased 2.3 fold in PBX1-overexpressing cells.",
    "ncbi_link": "PBX1: 5087"
  },
  {
    "caption": "(D) TH+cells derived from the PBX1-overexpressing hNES cells were also positive for mDAn markers such as LMX1A and PITX3. All scale bars, 40µm. Error bars represent mean ± standard deviation. Biological replicates per condition and p-value (T-test) are indicated in the graphs.",
    "ncbi_link": "PBX1: 5087"
  },
  {
    "caption": "(E) ChIP followed by PCR confirmed that PBX1 binds to genomic regions in close proximity to the TSS of Pitx3 (Pitx3-Gbf1), Onecut2and Nfe2l1 genes. No co-immunoprecipitation was detected for the unrelated gene, Lrp1b (Low Density Lipoprotein Receptor-Related Protein 1B).",
    "ncbi_link": "Gbf1: 107338
Lrp1b: 94217
Nfe2l1: 18023
Onecut2: 225631
Pitx3: 18742"
  },
  {
    "caption": "(F, G) The regulation of Pitx3 and Onecut2 by PBX1 was confirmed in Pbx1-/-;Pbx3+/- mutant embryos at E12.5, compared to wild-type (Pbx1+/+) littermates. (F) Representative immunofluorescence microscopy/confocal images showing that decreased levels of PITX3 and number of PITX3+cells in E12.5 Pbx1-/-;Pbx3+/- embryos. This reduction is more evident in the basal plate (BP) and in the midline (M), as shown at higher magnification (right). (G) Double ONECUT2+TH+cells were detected only in the lateral part of the mFP in E12.5 Pbx1-/-;Pbx3+/- embryos. Selected areas are magnified to the right. A scheme (right) shows the distribution of cells in Pbx1+/+ and Pbx1-/-;Pbx3+/- embryos. All scale bars, 40µm. Error bars represent mean ± standard deviation. Biological replicates (dots) per condition and p-value (T-test) are indicated in each graph.",
    "ncbi_link": "Pbx1: 18514
PBX1: 18514
Pbx3: 18516"
  },
  {
    "caption": "(B) The expression of NFE2L1 in TH+neurons is dramatically reduced in Pbx1-/-;Pbx3+/- compared to Pbx1+/+ embryos at E12.5",
    "ncbi_link": "Pbx1: 18514
Pbx3: 18516"
  },
  {
    "caption": "(C) shRNA lentiviruses against NFE2L1 increased the levels of aCASP3 in H2O2-treated (100µm for 12 hours) TH+neurons derived from hNES cells differentiated for 8 days (percentage). White arrows indicate double TH+aCASP3+neurons.",
    "ncbi_link": "NFE2L1: 4779"
  },
  {
    "caption": "(D) PBX1 overexpression protected TH+neurons derived from hNES cells from the oxidative stress induced by H2O2 (100µm for 12 hours), resulting in reduced levels of aCASP3 in TH+neurons (percentage).",
    "ncbi_link": "PBX1: 5087"
  },
  {
    "caption": "VGLL4 protein levels were reduced in Vgll4 depleted cells. Total cell lysates of Vgll4-knockdown LLC and MB49 cells were analyzed by western blot",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Control or shVgll4 LLC cells were transplanted into C57BL/6 mice, and tumor-growth kinetics was measured at the indicated times. n=12 tumors for each group",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Quantification of tumor weights 21 days after transplantation of control or shVgll4 LLC cells into C57BL/6 mice from (C)",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Control or shVgll4 LLC cells were transplanted into nude mice, and tumor-growth kinetics was measured at the indicated times. n=8 tumors for each group. (F) Quantification of tumor weights 15 days after transplantation of control or shVgll4 LLC cells into nude mice from (E). n=8 tumors for each group. n.s. p>0.05, two-tailed Student"s t-test. The solid line represents the average weight",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Control or shVgll4 MB49 cells were transplanted into C57BL/6 mice, and tumor-growth kinetics was measured at the indicated times. n=9 tumors for each group Quantification of tumor weights 30 days after transplantation of control or shVgll4 MB49 cells into C57BL/6 mice",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Control or shVgll4 MB49 cells were transplanted into nude mice, and tumor-growth kinetics was measured at the indicated times. n=8 tumors for each group Quantification of tumor weights 15 days after transplantation of control or shVgll4 MB49 cells into nude mice from (I). n=8 tumors for each group",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Immunofluorescent staining of CD3, CD8 and CD45 (red) counterstained with DAPI for DNA (blue) using control or shVgll4 LLC tumors from C57BL/6 mice. Statistical analysis of the percentage of CD3, CD8 and CD45 positive cells in the tumors is shown in the right panel respectively. n=3 tumors for each group",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Quantification of tumor weights 30 days after transplantation of shVgll4 MB49 cells into C57BL/6 mice receiving anti-CD4 alone, anti-CD8 alone, or both anti-CD4 and anti-CD8 blocking antibodies. n=20 tumors for each group",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Relative mRNA levels of immune related genes in Vgll4-knockdown LLC or MB49 cells by qRT-PCR analysis",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Knockdown of Vgll4 in MB49 cells decreased the surface expression of PD-L1 protein on control or shVgll4 MB49 cells measured by flow cytometry analysis with anti-mPD-L1 antibody",
    "ncbi_link": "Vgll4: 232334"
  },
  {
    "caption": "Relative mRNA levels of immune related genes in Vgll4-knockdown A549 cells by qRT-PCR analysis",
    "ncbi_link": "Vgll4: 9686"
  },
  {
    "caption": "Immunoblot analysis revealed the reduced expression of PD-L1 protein in VGLL4 knockdown A549, 16HBE and H358 cells compared with control cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "qRT-PCR analysis revealed a reduction of PD-L1 mRNA levels in VGLL4-knockdown 16HBE and H358 cells by siRNA",
    "ncbi_link": "PD-L1: 29126
VGLL4: 9686"
  },
  {
    "caption": "Flow cytometry analysis of surface PD-L1 levels in control and VGLL4 knockdown A549 cells treated with IFNγ for the indicated times",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Immunoblot analysis revealed the reduced IFNγ-inducible PD-L1 expression in VGLL4 knockdown A549 and 16HBE cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Immunoblot analysis of total cell lysates with the indicated antibodies revealed the attenuated IFNγ-inducible PD-L1 expression in VGLL4 knockout (KO) A549 cells generated by CRISPR/Cas9",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Loss of VGLL4 dampened the activity of PD-L1 promoter reporter in a luciferase assay. A549 cells were transfected with human PD-L1-promoter luciferase plasmid and indicated siRNA, treated with IFNγ for 12 h, and subjected to a luciferase assay",
    "ncbi_link": "luciferase: 
PD-L1: 29126
VGLL4: 9686"
  },
  {
    "caption": "Overexpression of mouse PD-L1 in Vgll4 knockdown LLC cells restored the tumor growth in C57BL/6 mice. Tumor weights of shVgll4 or shVgll4-lenti-mPD-L1 LLC cells were determined 21 days after tumor cell transplantation into C57BL/6 mice (left panel). Expression of mPD-L1 was shown in the right panel by immunoblot analysis with anti-mPD-L1 antibody. n=10 tumors for each group",
    "ncbi_link": "PD-L1: 60533
Vgll4: 232334"
  },
  {
    "caption": "Knockdown of VGLL4 in A549 cells enhances T cell-meditated tumor cell killing. Activated T cells and A549 cells were co-cultured in 24-well plates for 4 days and then surviving tumor cells were visualized by crystal violet staining. Relative fold ratios of surviving cell intensities are shown in right panel",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "The endogenous IRF2BP2 was immunoprecipitated by VGLL4-FLAG proteins in HEK293T cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "TDU-deleted or HF4A VGLL4 mutations interacted with IRF2BP by co-immunoprecipitation analysis in HEK293T cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "TDU-deleted or HF4A VGLL4 mutations interacted wit IRF2BP by co-immunoprecipitation analysis in HEK293T cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Expression of VGLL4-WT or VGLL4-HF4A enhances PD-L1 expression in A549 cells by immunoblot analysis. A549 cells were transfected with indicated plasmids and subjected to immunoblot with indicated antibodies",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "VGLL4-HF4A rescues PD-L1 expression in VGLL4-knockdown A549 cells. A549 cells were transfected with siRNA targeting to the 3"UTR of VGLL4 mRNA and followed by transduction with lenti-VGLL4-HF4A virus. Cell lysates were analyzed by western blot with indicated antib",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Expression of VGLL4-HF4A rescues tumor growth of VGLL4-knockdown LLC cells in C57BL/6 mice. Control, Vgll4 knockdown or Vgll4 knockdown together with VGLL4-HF4A overexpressing LLC cells were transplanted into nude mice or C57BL6 mice. Tumor volumes were measured 15 days for nude mice and 21 days for C57BL/6 mice after tumor cell inoculation",
    "ncbi_link": "VGLL4: 9686
VGLL4: 232334
Vgll4: 232334"
  },
  {
    "caption": "Expression of VGLL4-HF4A attenuates the T cell-meditated tumor cell killing. Activated T cells and A549 cells were co-cultured in 24-well plates for 4 days and Relative fold ratios of surviving cells are shown by measuring the intensities of surviving cells stained with crystal violet",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Immunoblot analysis of A549 cells transfected with VGLL4-FLAG or VGLL4-HF4A plasmids revealed an increased IRF2BP2 protein levels compared with control cells",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Deficiency of VGLL4 reduces IRF2BP2 protein levels. Immunoblot analysis of A549 and LLC cell lysates transfected with siRNA for control and VGLL4",
    "ncbi_link": "VGLL4: 9686
VGLL4: 232334"
  },
  {
    "caption": "The indicated cell lines were transfected with control or VGLL4 siRNA and subjected to immunoblot analysis with the indicated antibodies",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "qRT-PCR analysis of IRF2BP2 mRNA levels in control and siVGLL4 A549 cells",
    "ncbi_link": "IRF2BP2: 359948
VGLL4: 9686"
  },
  {
    "caption": "A549 or 16HBE cells were transfected with control or VGLL4 siRNA and treated with MG132 for the indicated times and subjected to immunoblot analysis with the indicated antibodies. Relative IRF2BP2 expression levels were quantified in the right panel",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Lys48-linked ubiquitylation of IRF2BP2 is strongly inhibited when VGLL4 was overexpressed in HEK293T cells. HEK293T cells were transfected with indicated plasmids, treated with MG132 for 3 h before harvest, and subjected to immunoprecipitation and immunoblot analysis as indicated",
    "ncbi_link": "IRF2BP2: 359948
VGLL4: 9686"
  },
  {
    "caption": "Lys48-linked ubiquitylation of IRF2BP2 is increased in the absence of VGLL4 in HEK293T cells. HEK293T cells were transfected with indicated siRNA and plasmids, and subjected to immunoprecipitation and immunoblot analysis as indicated",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "IRF2 inhibits IRF1 transcriptional activity. A549 cells transfected with human PD-L1 promoter luciferase reporter and indicated plasmids were analyzed using a luciferase assay",
    "ncbi_link": "PD-L1: 29126
IRF2: 3660"
  },
  {
    "caption": "Knockdown IRF2 restores PD-L1 expression in VGLL4-knockdown A549 cells. Gene expression levels were analyzed by qRT-PCR in A549 cells transfected or transduced as indicated",
    "ncbi_link": "PD-L1: 29126
IRF2: 3660
VGLL4: 9686"
  },
  {
    "caption": "Overexpression of IRF1 increases PD-L1 expression in VGLL4-knockdown A549 cells. A549 cells were transfected with VGLL4 siRNA or together with HA-IRF1 plasmid and total cell lysates were analyzed by western blot",
    "ncbi_link": "IRF1: 3659
VGLL4: 9686"
  },
  {
    "caption": "IRF2 is released from PD-L1 promoter upon IFNγ stimulation. IRF2-3×HA knockin A549 cells were stimulated with IFNγ and subjected to ChIP-qPCR analysis in the PD-L1 promoter using control and HA antibodies. Normal mouse IgG was used as control",
    "ncbi_link": "PD-L1: 29126
IRF2: 3660"
  },
  {
    "caption": "Increased association of IRF2 with PD-L1 promoter in IRF2BP2 knockout (KO) A549 cells revealed by ChIP-qPCR analysis. Immunoblot showed the loss of IRF2BP2 in IRF2BP2 KO A549 cells in the lower panel",
    "ncbi_link": "PD-L1: 29126
IRF2BP2: 359948"
  },
  {
    "caption": "Dynamic association of IRF2 with IRF2BP2 during IFNγ stimulation by immunoprecipitation analysis using anti-HA antibody in IRF2-3×HA knockin A549 cells",
    "ncbi_link": "IRF2: 3660"
  },
  {
    "caption": "Loss of IRF2BP2 attenuated IFNγ-inducible PD-L1 protein expression revealed by immunoblot in A549 control and IRF2BP2 knockout cells Quantification of PD-L1 protein level",
    "ncbi_link": "IRF2BP2: 359948"
  },
  {
    "caption": "Loss of IRF2BP2 attenuated IFNγ-inducible PD-L1 mRNA expression revealed by qRT-PCR analysis in A549 control and IRF2BP2 knockout cells",
    "ncbi_link": "PD-L1: 29126
IRF2BP2: 359948"
  },
  {
    "caption": "miR-130a represses VGLL4 and PD-L1 protein levels. A549 cells were transfected with control and miR-130a mimic and subjected to immunoblot analysis",
    "ncbi_link": "miR-130a: 406919"
  },
  {
    "caption": "Inhibition of miR-130a by its sponge enhances IFNγ-inducible PD-L1 expression. A549 cells were transduced with control or miR-130a sponge lentivirus and subjected to immunoblot",
    "ncbi_link": "miR-130a: 406919"
  },
  {
    "caption": "Inhibition of miR-130a by its sponge enhances IFNγ-inducible PD-L1 expression. A549 cells were transduced with control or miR-130a sponge lentivirus and subjected t qRT-PCR analysis",
    "ncbi_link": "PD-L1: 29126
miR-130a: 406919"
  },
  {
    "caption": "Decreased YAP target gene expression by inhibition of miR-130a using its sponge in A549 cells",
    "ncbi_link": "miR-130a: 406919"
  },
  {
    "caption": "YAP5SA expression attenuates IFNγ-inducible PD-L1 expression. A549 cells were transduced with control, YAP-5SA or YAP-S94A lentivirus and treated with IFNγ for the indicated times and subjected to immunoblot analysis",
    "ncbi_link": "YAP: 
YAP: 10413"
  },
  {
    "caption": "qRT-PCR analysis of cell lysates from control, YAP-5SA or YAP-S94A expressing A549 cells treated with IFNγ for the indicated times",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Control or YAP-overexpressing LLC cells were transplanted into nude mice (upper panel) or C57BL/6 (lower panel) mice, and tumor-growth kinetics was measured at the indicated times. Tumor volumes at the end time points were analyzed and shown at the right panel",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "miR-130a regulates IRF1 3′UTR sensor activity. A549 cells were transfected with WT or mutant IRF1 3′UTR sensor plasmids together with miR-130a mimic. Sensor activities were determined by dual luciferase assay",
    "ncbi_link": "IRF1: 3659
miR-130a: 406919"
  },
  {
    "caption": "YAP5SA induces miR-130a expression and represses IRF1 expression. A549 cells were transduced with control or YAP-5SA lentivirus and subjected to qRT-PCR  analysis",
    "ncbi_link": "IRF1: 3659
miR-130a: 406919
YAP: 10413"
  },
  {
    "caption": "Inhibition of miR-130a by its sponge enhances IFNγ-inducible IRF1 expression. A549 cells were transduced with control or miR-130a sponge lentivirus and subjected to qRT-PCR analysis",
    "ncbi_link": "IRF1: 3659
miR-130a: 406919"
  },
  {
    "caption": "Suppression of IFNγ-inducible PD-L1 expression by YAP5SA is compromised in miR-130a KO A549 cells. PD-L1 expression levels were analyzed by qRT-PCR in IFNγ-treated control or miR-130a KO A549 cells pre-transduced with lenti-YAP5SA virus",
    "ncbi_link": "PD-L1: 29126
miR-130a: 406919
YAP: 10413"
  },
  {
    "caption": "Kaplan-Meier survival analysis of patients with high (n=74) or low (n=130) VGLL4 mRNA levels from GSE31210, a lung cancer data set. Survival curves are calculated according to the Kaplan-Meier method",
    "ncbi_link": "VGLL4: 9686"
  },
  {
    "caption": "Representative time-lapse image series of exponentially growing M. smegmatis P2P1recA-GFPwt (C) and P2P1recA-GFPdes (D) reporters. Phase-contrast and green fluorescence are merged. Numbers represent hours. Scale bar, 10 µm. Histograms showing the distributions of single-cell fluorescence (n = 204) averaged over the lifetime of the cell (right panels). Black line indicates fitting of the data with a Lognormal function (C) or with the sum of three Gaussians (D). Insets: P2P1recA-GFPwt population's geometric mean (Gµ) calculated by computing the logarithm of the single-cell fluorescence values, the mean of the logarithms and its antilog, P2P1recA-GFPdes subpopulations' means (µ), and R2 values. The two distributions show that the destabilized GFPdes is more suitable to monitor the dynamics of recA expression and to detect subpopulations, which are masked by using the stable GFPwt variant. E Spearman's correlation between single-cell P2P1recA-GFPdes fluorescence range and VMR of fluorescence over the lifetime of the cell (n = 204). The data shown are from 3 independent experiments. Dashed lines separate different levels of fluorescence dispersion over the lifetimes of single-cells. Colors denote cells belonging to underdispersed (gray), dispersed (dark green), and highly dispersed (light green) subpopulations. F P2P1recA-GFPdes fluorescence range over the lifetime of the cell of subpopulations segregated by fluorescence VMR (40 < n < 112). The data shown are from 3 independent experiments. Black lines indicate means ± SD. Asterisks denote significant difference by Kruskal-Wallis and Dunn's multiple comparison test: ****p < 0.0001. G Single-cell time traces of P2P1recA-GFPdes fluorescence expressed as a percent of generation time of subpopulations segregated by fluorescence VMR. The average fluorescence (solid black lines) and half of the generation time (dashed lines) are indicated. Population statistics (n = 204): 38% (0<VMR≤1); 44% (1<VMR≤10); 18% (VMR>10). The data shown are from 3 independent experiments. H Histogram showing the distribution of the fluorescence peak time expressed as a percent of generation time. Dark green bars indicate moderately pulsing cells (n = 165). Light green bars indicate highly pulsing cells (n = 66). Significance by Mann-Whitney test. The data shown are from 3 independent experiments. Peaks mainly occur between 40% and 70% of the generation time.",
    "ncbi_link": "GFP: 
recA: 4532488"
  },
  {
    "caption": "Spearman's correlation between green (A-D) or yellow (E) fluorescence range and red fluorescence range over the lifetime of the cell (105 < n < 153). The data shown are from 2 independent experiments. On the x-axes P2P1recA-GFPdes (A-D) or a C-term translational reporter of SSBa fused to mCitrinewt (E). On the y-axes, a C-term translational reporter of RecA fused to mCherrywt (A and E), transcriptional reporters of ruvC (B) and radA (C), and mCherrydes expressed from a constitutive control promoter (D). Colors (A-D) indicate subpopulations segregated by VMR of P2P1recA-GFPdes: gray (0<VMR≤1), dark green (1<VMR≤10), and light green (VMR>10). Colors (E) indicate subpopulations segregated by VMR of RecA-mCherrywt: gray (0<VMR≤1), plum (1<VMR≤10), and magenta (VMR>10).",
    "ncbi_link": "GFP: 
mCherry: 
mCitrine: 
SSBa: 4534331
radA: 4535537
recA: 4532488
RecA: 4532488
ruvC: 4533548"
  },
  {
    "caption": "Pearson's correlation between green (F-I) or yellow (J) fluorescence and red fluorescence, measured 3 hours after MMC exposure (203 < n < 314). The data shown are from 2 independent experiments. On the x-axes P2P1recA-GFPdes (F-I) or a C-term translational reporter of SSBa fused to mCitrinewt (J). On the y-axes, a C-term translational reporter of RecA fused to mCherrywt (F and J), transcriptional reporters of ruvC (G) and radA (H), and mCherrydes expressed from a constitutive control promoter (I). Positive correlations between recA and other DNA-damage markers both under normal growth conditions, where spontaneous DNA-damage events occur at the subpopulation level, and in the presence of an alkylating agent that induces double-strand breaks in the entire population, validate recA as a reliable proxy for DNA damage in single cells.",
    "ncbi_link": "GFP: 
mCherry: 
mCitrine: 
SSBa: 4534331
radA: 4535537
recA: 4532488
RecA: 4532488
ruvC: 4533548"
  },
  {
    "caption": "Representative time-lapse image series of the merodiploid recA reporter strain (P2P1recA-GFPdes_RecA-mCherrywt) cultured in fresh (A) or spent (B) flow medium (see Materials and Methods). Fresh 7H9 medium is unlabeled; spent medium (S), ciprofloxacin 1 µg/ml in fresh (CIP) or spent (S-CIP) medium, and SYTOX 0.5 µM (SX) are labeled. Phase-contrast (gray), GFPdes (green), and mCherrywt (magenta) fluorescence are merged. Fluorescence images of each channel are scaled to the brightest frame. Light-green background in the first 4 frames (B) is due to the autofluorescence of spent medium. Cells were imaged at 30-min intervals and numbers represent hours. Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
mCherry: 
recA: 4532488
RecA: 4532488"
  },
  {
    "caption": "Representative GFPdes (G) and mCherrywt (H) fluorescence time-traces for single-cell lineages of cells cultured in fresh medium (EXP) and cells cultured in spent medium (STAT), and having different fates. Vertical bars are color-coded as in C and D.",
    "ncbi_link": "GFP: 
mCherry: "
  },
  {
    "caption": "Single-cell fate as a function of VMR of P2P1recA-GFPdes (I) and RecA-mCherrywt (J) fluorescence prior to CIP exposure. Significance by Chi-square test of independence for cells that die (n = 84) and cells that survive (n = 54). The data shown are from 2 independent experiments. Cells that do not experience DNA damage prior to drug exposure (RecA-non-pulsing cells) survive more than cells that do experience DNA damage (RecA-pulsing cells).",
    "ncbi_link": "GFP: 
mCherry: 
recA: 4532488
RecA: 4532488"
  },
  {
    "caption": "Spearman's correlation between single-cell RecA-mCherrywt fluorescence range and fluorescence VMR over the lifetime of the cell (n = 360). The data shown are from 3 independent experiments. Dashed lines separate different levels of dispersion, and colors denote subpopulations that are underdispersed (gray), dispersed (plum), or highly dispersed (magenta). RecA-mCherrywt fluorescence of subpopulations segregated by fluorescence VMR (58 < n < 159). The data shown are from 3 independent experiments. Black lines indicate means ± SD. Asterisks denote significant difference by Kruskal-Wallis and Dunn's multiple comparison test: ****p < 0.0001.",
    "ncbi_link": "mCherry: 
RecA: 4532488"
  },
  {
    "caption": "Single-cell time traces of RecA-mCherrywt fluorescence expressed as percent of generation time of subpopulations segregated by fluorescence VMR. The average fluorescence (solid black lines) and half of the generation time (dashed lines) are indicated. Population statistics (n = 360): 40% (0<VMR≤1); 44% (1<VMR≤10); 16% (VMR>10). The data shown are from 3 independent experiments.",
    "ncbi_link": "mCherry: 
RecA: 4532488"
  },
  {
    "caption": "Representative time-lapse image series of the dual reporter of RecA and rRNA expression in exponential phase. Pre-CIP growing (PG-S) and arrested (PA-S) survivors and resistant (R) cells are indicated by arrows. CIP exposure (1 µg/ml, 4X-MIC) and SX (0.5 µM) death assay (blue line) are indicated. Phase-contrast (gray), Prrn-GFPdes (green), and RecA-mCherrywt (magenta) fluorescence are merged. Fluorescence images of each channel are scaled to the brightest frame. Cells were imaged at 3-hour intervals and numbers indicate days. Scale bar, 5 µm.",
    "ncbi_link": "GFP: 
mCherry: 
rRNA: 
RecA: 4532488"
  },
  {
    "caption": "Comparison of growth rate (C), cell size averaged over the lifetime of the cell (D), microcolony size (E) before CIP exposure Gray and black lines indicate mean ± SD. The data shown are from 2 independent experiments. Significance by unpaired Mann-Whitney test: ns, not significant; **p = 0.001; ****p < 0.0001. Most survivors had a moderate growth defect before exposure to ciprofloxacin and lower expression of RecA-mCherrywt both before and after drug exposure.",
    "ncbi_link": "mCherry: 
RecA: 4532488"
  },
  {
    "caption": "fluorescence range over the lifetime of the cell before CIP exposure (F), and mean fluorescence during CIP exposure (G) of cells that died (n = 174) and cells that survived (n = 164). Gray and black lines indicate mean ± SD. The data shown are from 2 independent experiments. Significance by unpaired Mann-Whitney test: ns, not significant; **p = 0.001; ****p < 0.0001. Most survivors had a moderate growth defect before exposure to ciprofloxacin and lower expression of RecA-mCherrywt both before and after drug exposure.",
    "ncbi_link": "mCherry: 
RecA: 4532488"
  },
  {
    "caption": "Single-cell fate as a function of VMR of RecA-mCherrywt fluorescence prior to CIP exposure. Significance by Chi-square test of independence: cells that died (n = 174), cells that survived (n = 155), and resistant cells (n = 9). The data shown are from 2 independent experiments. More survivors arise from the subpopulation that does not experience DNA damage before drug exposure.",
    "ncbi_link": "mCherry: 
RecA: 4532488"
  },
  {
    "caption": "I The mRNA level of CD39, ENTPD2 and ENTPD3 in the hippocampus of susceptible mice after CSDS (n = 7, 8 mice. CSDS vs control, CD39 P = 0.0002, ENTPD2 P = 0.0025, Student's t test).",
    "ncbi_link": "CD39: 12495
ENTPD2: 12496
ENTPD3: 215446"
  },
  {
    "caption": "C Expression of CD39 in the hippocampus of mice injected with LV-siCD39 (n = 6 mice/group. LV-siCD39 vs Control, P = 0.0006, Student's t test).",
    "ncbi_link": "CD39: 12495"
  },
  {
    "caption": "D The social avoidance behavior for the stressed mice after knocking down CD39 (n = 15, 15, 14 mice. Interaction F2, 41 = 17.96, P < 0.0001; Target F1, 41 = 3.75e-005, P = 0.9951; Drug F2, 41 = 6.099, P = 0.0048; For Target CSDS - LV-GFP vs Ctrl - LV-GFP, P < 0.0001; CSDS - LV-siCD39 vs CSDS - LV-GFP, P < 0.0001. Two-way ANOVA with Tukey's post-test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "E The immobility time in the TST of mice injected with LV- siCD39 (n = 11, 19, 15 mice. Treatment F 2, 42 = 5.807, P = 0.0059; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0069; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0065. One-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "F The immobility time spent in the FST of mice treatment with LV-siCD39 (n = 12, 19, 15 mice. Treatment F2, 43 = 5.237, P = 0.0092; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0095; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0093. One-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "G The ATPase hyperactivity of mice after knocking down CD39 in the hippocampal (n = 5, 6, 5 mice. Treatment F2, 13 = 8.45, P = 0.0044; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0016; CSDS - LV-CD39 vs CSDS - LV-GFP, P = 0.0166. One-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "H The ATP level of mice after knocking down CD39 in the hippocampal (n = 5 mice/group. Treatment F2, 12 = 6.04, P = 0.0153; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0444; CSDS - LV-CD39 vs CSDS - LV-GFP, P = 0.0051. One-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "F Confocal images of BrdU (blue) and DCX (red) in mice treatment with LV-siCD39 in the DG. Arrows indicate the BrdU+ DCX+ cells. Scale bar: 50 μm.",
    "ncbi_link": "CD39: 12495"
  },
  {
    "caption": "G, H Quantitative of BrdU+ (G) and BrdU+ DCX+ (H) cells in the DG of susceptible mice with LV-siCD39 compared with LV-GFP treatment (n = 3, 6, 6 mice. For BrdU+ Treatment F2, 12 = 15.79, P =0.0004; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.0012; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0003; BrdU+ DCX+ Treatment F2, 12 = 12.79, P = 0.0011; CSDS - LV-GFP vs Ctrl - LV-GFP, P = 0.05; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0003, one-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "B-E Quantification of total (B), stubby (C), mushroom (D) and thin (E) spine density in DG from control and susceptible mice infected with LV-GFP or LV-siCD39 (n = 15 segments from 4 mice/group. For total density: Treatment F2, 42 = 3.12, P = 0.0544; Ctrl - LV-GFP vs CSDS - LV-siCD39, P = 0.0312; CSDS - LV-siCD39 vs CSDS - LV-GFP, P = 0.0425; stubby density: Treatment F2, 42 = 10.93, P=0.0002; P = 0.0026; CSDS - LV-CD39 vs CSDS - LV-GFP, P < 0.0001; mushroom density: Treatment F2, 42 = 0.34, P = 0.7161; thin density: F2, 42 = 1.00, P = 0.3758. One-way ANOVA with Fisher's LSD test).",
    "ncbi_link": "GFP: 
CD39: 12495"
  },
  {
    "caption": "A. qPCR  of TREM1  and genes involved in neutrophil  recruitment demonstrate increased expression  in healing DFUs  compared to nonhealing DFUs  (n = 5 healing   and n= 6 nonhealing). Data presented as mean ± SD. *P < 0.05. **P < 0.01 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "TREM1: 54210"
  },
  {
    "caption": "Induction of UAS constructs and EPs by the ap promoter directed Gal4 expression within the dorsal compartment of the wing imaginal disc: (A) ap-Gal4 control; (B, E, H, J, K) UAS-dS6K; (C, F, I) UAS-S6K1dE/D3E; (D, E, F) DHR3-EP; (G, H, I, K) UAS-DHR3-RNAi and (J) unidirectional DHR3-EP. The bending down of the wing indicates a slight overgrowth of the dorsal compartment, whereas a bending up reveals a slight growth deficit of this compartment.",
    "ncbi_link": "Gal4: 
ap: 35509
DHR3: 36073
S6K1: 6198
dS6K: 38654"
  },
  {
    "caption": "Induction of UAS constructs and DHR3-EP by the eyeless promoter-directed Gal4 expression in the developing eye: (A) eye-Gal4 control; (B, D, E) DHR3-EP; (C, D) UAS-dTsc1 and UAS-dTsc2; (E, F) UAS-dPTEN.",
    "ncbi_link": "Gal4: 
eye: 43812
dTsc2: 40201
DHR3: 36073
dPTEN: 43991
dTsc1: 42862"
  },
  {
    "caption": "(B-G) Adult wings in which the ap-Gal4 induces expression of the following UAS constructs: (B) ap-Gal4 control; (C) UAS-dS6K; (D) UAS-DHR3-RS; (E) both UAS-dS6K and UAS-DHR3-RS; (F) UAS-DHR3-RS in a dS6Kl-1 mutant escaper; (G) UAS-dS6K, UAS-DHR3-RS, and UAS-DHR3-RNAi together.",
    "ncbi_link": "Gal4: 
ap: 35509
DHR3: 36073
dS6K: 38654"
  },
  {
    "caption": "(H) Upper panel, H2B substrate phosphorylation by dS6K from larval protein extracts. Ubiquitous induction of UAS-DHR3 RNAi, using either a daughterless-Gal4 (da>Ri) or an actin-Gal4 (ac>Ri) driver, provoked a drop in dS6K activity, as compared with control drivers alone (da, ac). Middle and lower panels are western blots detecting dS6K and α-tubulin, respectively.",
    "ncbi_link": "actin: 
Gal4: 
daughterless: 34413
DHR3: 36073"
  },
  {
    "caption": "(A-F) Wing imaginal discs stained with: (A, C, D, F) antibody to DHR3, and (B, E) antibody to GFP. (A, B) Overexpression of DHR3-RS and USA-GFP in the posterior compartment was induced using an engrailed-Gal4 driver. (C) and (D) ap-Gal4 drives overexpression of DHR3-RS and DHR3-EP, respectively. (E, F) Flip-out clone (induced 3 days prior to dissection) in a prepupal wing imaginal disc expressing UAS-DHR3-RNAi and UAS-GFP. (E) Decrease in DHR3 staining in a flip-out clone labeled by GFP (F), indicating that DHR3 is expressed in this tissue.",
    "ncbi_link": "Gal4: 
ap: 35509
engrailed: 36240
DHR3: 36073"
  },
  {
    "caption": "(G) Western blot analysis of DHR3 in larval protein extracts from control (Co) and heat shock-induced UAS lines expressing DHR3-RA (RA), DHR3-RB (RB), and DHR3-RS (RS) transcripts, or the DHR3-EPs (E1 and E2).",
    "ncbi_link": "DHR3: 36073"
  },
  {
    "caption": "(H) Western blot of the endogenous DHR3 protein in late third-instar larvae (L3), prepupae (pp), and prepupae expressing an RNAi to DHR3 (RNAipp). In (G, H), the arrows at the left indicate the position of the DBD-containing (high) and DBD-lacking (low) DHR3 proteins.",
    "ncbi_link": "DHR3: 36073"
  },
  {
    "caption": "(A, B) The ap-Gal4 driver induces dS6K in combination with either (A) the DHR3-EP transgene or (B) the EP with the EMS DHR3 mutation",
    "ncbi_link": "Gal4: 
ap: 35509
DHR3: 36073
dS6K: 38654"
  },
  {
    "caption": "(F, G) The eyeless promoter directs the flipase recombinase during eye development. Flipase allows recombination on the right arm of the second chromosome and eventually leads to an adult eye (F) that is homozygous for the wild-type allele of DHR3. (G) Homozygosity for a DHR3K243X mutation results in a decrease in the size of the adult eye. A dotted yellow line surrounding the control eye in (F) has been copied and pasted on the mutant eyes (G); insets are higher magnification images of ommatidia showing misorientation of bristles.",
    "ncbi_link": "eyeless: 43812
DHR3: 36073"
  },
  {
    "caption": "(H) At the scutellum, a y-marked homozygous DHR3K243X mutant bristle (arrow), recognizable by its light color, is smaller than the symmetrical neighboring bristles.",
    "ncbi_link": "DHR3: 36073"
  },
  {
    "caption": "(A) Normalized eye size (mm2) of control (black bar; n = 20), DHR3W284X (grey bar; n = 18) and DHR3K243X (white bar; n = 18) mutants. As compared to control recombined eyes (Co), DHR3W284X and DHR3K243X mutant eyes exhibit a highly significant size reduction (***P<0.001). (B) Ommatidia size of control (black bar), DHR3W284X (grey bar), and DHR3K243X (white bar) mutants. As compared to control recombined eyes (Co), DHR3W284X and DHR3K243X mutant ommatidia exhibit a significant size reduction (**P<0.01).",
    "ncbi_link": "DHR3: 36073"
  },
  {
    "caption": "(C-E) Comparison of y-marked homozygous clonal bristles (black arrows) to their neighboring heterozygous bristles (white arrows) at the wing margin. Note that control clonal bristles are of normal size and orientation (C), whereas those of DHR3W284X (D) and DHR3K243X (E) are reduced in size and are misoriented. (F) Size measurements (µm) of the length of homozygous clones (y−) and their neighboring heterozygous (y+) bristles (n = 51 for each bar). The size reduction of clonal versus neighbor bristles is highly significant for DHR3K243X (***P<0.001) and DHR3W284X (***P<0.001) mutants, but not for the control (Co) bristles (P = 0.028).",
    "ncbi_link": "DHR3: 36073"
  },
  {
    "caption": "MCF10A cells were treated with 5uM RSL3 for times that ranged from 0 to 120 minutes. mRNA was isolated from each time point and PROM2 expression was quantified by qPCR. Shown is an average of three independent experiments with standard deviation (n=3 experiments per time point). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. Exact p‑values are reported in the Appendix Table S1. MCF10A cells were pretreated for 15 minutes with either DMSO or 2uM fer-1, followed by 60 minutes with either DMSO, 5uM RSL3 or RSL3 and fer-1. mRNA was isolated and PROM2 expression was quantified by qPCR. Shown are three independent experiments with standard deviation (n=3 experiments per group). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. Exact p‑values are reported in the Appendix Table S1. MCF10A cells were treated with 25uM 4HNE for times that ranged from 0 to 120 minutes. mRNA was isolated from each time point and PROM2 expression was quantified by qPCR. Shown is an average of three independent experiments with standard deviation (n=3 experiments per time point). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. Exact p‑values are reported in the Appendix Table S1. MCF10A cells were pretreated for 15 minutes with either DMSO or 2uM fer-1, followed by 60 minutes with either EtOH, 25uM 4HNE or RSL3 and fer-1. mRNA was isolated and PROM2 expression was quantified by qPCR. Shown are three independent experiments with standard deviation (n=3 experiments per group). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. n=3 experiments per group. Exact p‑values are reported in the Appendix Table S1.",
    "ncbi_link": "PROM2: 150696"
  },
  {
    "caption": "HSF1 expression was diminished in MCF10A cells for 48 hours using siRNA prior to treatment with either DMSO, EtOH, DMSO, 25uM 4HNE or 5uM RSL3. Isolated protein was assessed by immunoblotting for prominin2, phospho-HSF1 (Ser326), total HSF1, phospho-p38 (Thr180/Tyr182), total p38, and β-actin expression. Shown is one replicate of three independent experiments (n=3).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "MCF10A cells were treated for 60 minutes with either DMSO, 25uM 4HNE, 5uM RSL3, 4HNE and 10uM KRIBB11 or RSL3 and KRIBB11. mRNA was isolated and PROM2 expression was quantified by qPCR. Shown are three independent experiments with standard deviation (n=3 experiments per group). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. Exact p‑values are reported in the Appendix Table S1. MCF10A cells were treated for 60 minutes with either DMSO, 25uM 4HNE, 5uM RSL3, 4HNE and 10uM KRIBB11 or RSL3 and KRIBB11. mRNA was isolated and HSF1 expression was quantified by qPCR. Shown are three independent experiments with standard deviation (n=3 experiments per group). P‑values were obtained by unpaired Student's t‑test with *P<0.05, **p<0.01, ***p<0.005. Exact p‑values are reported in the Appendix Table S1.",
    "ncbi_link": "HSF1: 3297
PROM2: 150696"
  },
  {
    "caption": "A Indicated tail-anchored (TA) proteins were in vitro translated in rabbit reticulocyte lysate (RRL) using RNAs containing a stop codon. Translations were carried out in the presence of 2 μM HisTrx or HisTrx-SGTA (HT-SGTA), followed by incubation with HisPur Cobalt resin Bound proteins were eluted at high imidazole concentration, samples resolved by SDS-PAGE and results visualised by phosphorimaging. Sec61β 3R carries three Arg residues within Sec61β transmembrane domain (TMD) which abolish its hydrophobic character and was used as a negative control for SGTA binding. A schematic representation of a TA-protein is also shown. Open circles indicate TA-proteins selectively bound by HisTrx-SGTA. RAMP4 - stress-associated endoplasmic reticulum protein 1; Syb2 - synaptobrevin 2; Synt5 - syntaxin 5. B As for (A) but total translation products (input) were resolved by SDS-PAGE and results visualised by phosphorimaging. When total products are analysed high amounts of haemoglobin in the RRL distort the migration of Sec61β and its variant. ",
    "ncbi_link": "Sec61β: 10952"
  },
  {
    "caption": "Sec61β wild-type (WT) and the 3R variant tagged at their N-terminus with the FLAG epitope were translated in RRL from RNAs lacking a stop codon. Ribosome-nascent chain complexes (RNCs) were recovered using anti-FLAG affinity resin, beads were washed, bound proteins eluted with 3xFLAG peptide and RNCs isolated by pelleting through a sucrose cushion Samples were resolved by SDS-PAGE and immunoblotted for endogenous rabbit SGTA, FLAG-tagged translation products, proteins of the 40S (Rps3) and 60S (Rpl17) ribosomal subunits or analysed by phosphorimaging (35S). The 3xFLAG peptide eluted material (lanes 4 and 5) corresponds to ~10% of the sedimented RNCs (lanes 7 and 8).",
    "ncbi_link": "FLAG: 
Sec61β: 10952"
  },
  {
    "caption": "C PPL-C99FL variants lacking a stop codon and carrying the indicated Lys to Arg substitutions were in vitro translated in the presence of 2 μM HisTrx-SGTA. Reactions were processed using chicken anti-SGTA antibody for immunoprecipitation of SGTA adducts. D Cross-linking adducts between ribosome-stalled PPL-C99FL lysine mutants and recombinant HisTrx-SGTA shown in panel (C) were quantified, any differences in translation efficiency accounted for and cross-linking efficiency expressed relative to the wild-type (WT) protein. Shown is the mean with standard error of mean for n=3 biological replicates. Statistical significance was calculated using unpaired t test with Welch's correction.",
    "ncbi_link": "PPL: 280901"
  },
  {
    "caption": "A Body weight of male wildtype and Vil-Ogt KO mice at 6 weeks of age (n = 6, P = 0.000015) ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": "B Incidence of rectal prolapse in male wildtype and Vil-Ogt KO mice (WT n = 17, KO n = 9, P < 0.0001) ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " C Representative colonoscopy images of male wildtype and Vil-Ogt KO mice ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " D Body weight of female wildtype and Vil-Ogt KO mice at 9 weeks of age (WT n = 11, heterozygous KO n = 4, homozygous KO n = 5, P < 0.0001) ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " E Incidence of rectal prolapse in female wildtype and Vil-Ogt KO mice (WT n = 9, heterozygous KO n = 8, homozygous KO n = 6, P = 0.0439)",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " F H&E staining of duodenum, jejunum, ileum, colon, and rectum of 10-week-old male wildtype and Vil-Ogt KO mice. Scale bars = 100 μm ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " A Numbers of Paneth cells in the ileum of wildtype and Vil-Ogt KO mice (n = 6, P = 0.0048) ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " C Expression of AMP genes in ileum tissues of wildtype and Vil-Ogt KO mice (n = 6, Pan Defesin P = 0.031, Defa3 P = 0.049, Defa4 P = 0.013, Defa5 P = 0.023, Defa6 P = 0.034, Ang4 P = 0.031) ",
    "ncbi_link": "Pan Defesin: 
Ang4: 219033
Defa3: 13237
Defa4: 13238
Defa5: 13239
Defa6: 13240
Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " D Immunoblotting of LC3 in IEC cells isolated from WT and Vil-Ogt KO mice ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " E Representative images of O-GlcNAc staining in Paneth cells  of male wildtype and Defa6-Ogt KO mice. Stars indicate lysozyme-positive Paneth cells ",
    "ncbi_link": "Defa6: 13240
Ogt: 108155"
  },
  {
    "caption": " F Morphology and numbers of Paneth cells in the ileum of wildtype and Defa6-Ogt KO mice (n = 5, P = 0.024). Arrow indicate Paneth cell. Scale bars = 10 μm ",
    "ncbi_link": "Defa6: 13240
Ogt: 108155"
  },
  {
    "caption": " G Expression of AMP genes in the ileum of wildtype and Defa6-Ogt KO mice (n = 5 Pan Defesin P = 0.0291, Defa3 P = 0.0462) ",
    "ncbi_link": "Pan Defesin: 
Defa3: 13237
Defa6: 13240
Ogt: 108155"
  },
  {
    "caption": " I Expression of inflammatory markers in the ileum of wildtype and Defa6-Ogt KO mice (n = 5) ",
    "ncbi_link": "Defa6: 13240
Ogt: 108155"
  },
  {
    "caption": " J-L Antibiotic-treated wildtype and Defa6-Ogt KO male mice were transplanted with fecal microbiota from Vil-Ogt KO mice and then induced with DSS for colitis. Daily changes in body weight (J) are shown (n = 4-5). (L: P = 0.049",
    "ncbi_link": "Defa6: 13240
Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " J-L Antibiotic-treated wildtype and Defa6-Ogt KO male mice were transplanted with fecal microbiota from Vil-Ogt KO mice and then induced with DSS for colitis. Daily changes i colitis scores (K are shown (n = 4-5). (L: P = 0.049",
    "ncbi_link": "Defa6: 13240
Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " J-L Antibiotic-treated wildtype and Defa6-Ogt KO male mice were transplanted with fecal microbiota from Vil-Ogt KO mice and then induced with DSS for colitis RT-qPCR of inflammatory genes in the ileum (L) are shown (n = 4-5). (L: P = 0.049",
    "ncbi_link": "Defa6: 13240
Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " A Expression of phosphorylated and total STAT3 and NF-κB p65 in the colon of wildtype and Vil-Ogt KO mice ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " B Ileum and colon IECs from 10-week-old wildtype and Vil-Ogt KO mice were isolated for RNA-sequencing analyses. The heatmaps of the sample-to-sample distances are shown ",
    "ncbi_link": "Ogt: 108155
Vil: 22349"
  },
  {
    "caption": " I siRNAs against scrambled sequence or human OGT were transfected in 293T cells and STAT1 levels were determined 48 hours later ",
    "ncbi_link": "OGT: 8473"
  },
  {
    "caption": " J The pGAS-luc Cis-Reporter plasmid was co-transfected with siRNAs in 293T cells for luciferase assay  to determine the transcriptional activity of STAT1 (n = 4, P=0.0003) ",
    "ncbi_link": "luc: 
STAT1: 6772"
  },
  {
    "caption": "RT-qPCR of inflammatory genes in the colon (G) on day 4 of recovery (n = 5). Scale bars = 100 μm. (E: P = 0.0474; G: Tnfa P = 0.0190, Il1b P = 0.0301",
    "ncbi_link": "Il1b: 16176
Tnfa: 21926"
  },
  {
    "caption": "(G) Schematic illustration for the experiments shown in H, I. (H) Representative images of chromosome spreads after re-expression of endogenous CENP-AEA into a CENP-AmRFP-DHFR overexpression background and subsequent removal of the overexpression as illustrated in (G). Antibody against CENP-C was used to score for the presence of the functional centromere. Scale bar, 5µm. (I) Quantification of the indicated events after one CENP-AOFF/ON cycle compared to treatment shown in (G). ",
    "ncbi_link": "mRFP: 
CENP-A: 1058
DHFR: 1719"
  },
  {
    "caption": "(A) Schematic illustration of the CENP-AOFF/ON cycle performed in the experiments shown in B, C. (B) Representative images of de novo CENP-A reloading in CENP-B wild-type (+/+) and CENP-B knock-out (-/-) cells. Cells with centromeric CENP-A are marked with a red dashed contour line while a yellow contour lines mark cell without centromeric CENP-A. Scale bar, 5 µm. (C) Quantification of relative number of RPE-1 cells with centromeric CENP-A in the indicated conditions. Each dot represents one experiment with at least 20 cells per condition. Error bars represent standard error of the mean (SEM) from 3 independent experiments. ",
    "ncbi_link": "CENP-A: 1058
CENP-B: 1059"
  },
  {
    "caption": "(E) Representative images of DLD-1 CENP-B (+/+) or (-/-) cells in late M phase following one CENP-AOFF/ON cycle. EdU staining was used to confirm successful wash-out of Palbociclib and cell progressing through S-phase. Yellow dashed lines contour nucleus of cells in late M phase. Scale bar 5 µm. (F) Quantification of indicated events observed in late M phase cells in the indicated cell lines. Error bars show SEM from 4 independent experiments. ",
    "ncbi_link": "CENP-B: 1059"
  },
  {
    "caption": "(C) Representative IF-FISH images of mitotic spreads in non-treated cell (NT) and following a CENP-AOFF/ON cycle (IAA WO). Chromosomes are contoured by a green (X), magenta (Y) or white (other autosomes) dashed line. The centromeres of chromosome X/Y are highlighted by a green/magenta arrow. Scale bar, 2 µm.",
    "ncbi_link": "CENP-A: 1058"
  },
  {
    "caption": "(D) Quantification of CENP-C (as read-out of CENP-A) presence at the X (green) or Y (magenta) centromere in the indicated cell lines. Each dot represents one experiment. Error bars represent SD from 3 independent experiments. Unpaired t test, **p=0.0042.",
    "ncbi_link": "CENP-A: 1058"
  },
  {
    "caption": "(G) Representative IF-FISH images showing CENP-C localization on the Y chromosome in cell growing under selective pressure (G418) following a CENP-AOFF/ON cycle. Chromosomes are highlighted by a white dashed contour line. CENP-C was found at the native centromere position (top panel, blue), the Y chromosome fused to another chromosome indicated by the increased size of the chromosome and the absence of Chr-Y painting probe staining (second panel, orange) or CENP-C was found on a different location on the Y chromosome and did not overlap with Cen-Y DNA (lower panels, red). Scale bar, 2 µm. (H) Quantification of indicated events depicted in G. Each dot represents one experiment (>20 spreads for experiment). Error bars represent SEM from 3 independent experiments. Unpaired t-test, *p=0.0137 and 0.039. ",
    "ncbi_link": "CENP-A: 1058"
  },
  {
    "caption": "(B) Representative immunofluorescence images showing CENP-C recruitment at the LacO array in the indicated conditions. LacO array is displayed in the insets.",
    "ncbi_link": "LacO: "
  },
  {
    "caption": "(C) Bar plot showing frequency of CENP-C (orange) or CENP-A (green) recruitment to LacO array in the indicated conditions. Each dot represents one independent experiment (>20 cell analyzed for experiment).",
    "ncbi_link": "LacO: "
  },
  {
    "caption": "(D) Quantification of CENP-C (orange) or CENP-A (green) protein levels at the LacO array in the indicated conditions normalized to protein intensities in non-treated conditions at the mCherry-LacI-CENP-B-LacO array using CENP-A or CENP-C antibody. Each dot represents one independent experiment (>20 cell analyzed for experiment). Error bars represent SEM from 3 independent experiments.",
    "ncbi_link": "LacI: 
LacO: 
mCherry: 
CENP-B: 1059"
  },
  {
    "caption": "(E) Representative immunofluorescence images showing CENP-A recruitment to ectopic mCherry-LacI-CENP-B in the indicated conditions. LacO array is shown in the inset.",
    "ncbi_link": "LacI: 
LacO: "
  },
  {
    "caption": "(F) Quantification of the frequency of CENP-C recruitment to LacO arrays by different LacI constructs. Error bars represent SEM from 5 independent experiments.",
    "ncbi_link": "LacI: 
LacO: "
  },
  {
    "caption": "(E) Box plot of CUT&RUN qPCR for CENP-A (green) or CENP-C (orange). Box plot shows median, 25th and 75th percentiles, whiskers show minimum and maximum values. Results from 3 independent experiments including combined data from qPCR reactions using alpha-satellite primers and primers binding at the centromere of chromosome 4. Enrichment is measured relative to the IgG control and normalized to Alu repeats.",
    "ncbi_link": "CENP-A: 1058
CENP-C: 1060"
  },
  {
    "caption": "(E) Bar plot of CUT&RUN qPCR quantification using CENP-A antibody and primers binding at the centromere of chromosome 4. Enrichment is measured relative to the IgG control and normalized to Alu repeats.",
    "ncbi_link": "CENP-A: 1058"
  },
  {
    "caption": "(H) Bar plot of CUT&RUN qPCR results using CENP-C antibody and primers binding at the centromere of chromosome 4. Enrichment is measured relative to the IgG control and normalized to Alu repeats. Each dot represents one independent experiment.",
    "ncbi_link": "CENP-C: 1060"
  },
  {
    "caption": "B Fatty acid composition of B. subtilis WT cells grown in PF medium, and Δbkd grown with MB, IB or depleted for precursor for 90 min (IBPF). For detailed analyses, see Appendix Fig S1B.",
    "ncbi_link": "bkd: 938672///938674///938677///938666"
  },
  {
    "caption": "E Fatty acid composition of E. coli WT and fabA(Ts) cells grown at 30°C and shifted to different temperatures for 120 min. For detailed analyses, see Appendix Fig S2B and C.",
    "ncbi_link": "fabA: 945568"
  },
  {
    "caption": "A DPH anisotropy of B. subtilis WT or Δbkd cells supplemented either with MB, IB or depleted for precursor (IBPF) for the times indicated. High DPH anisotropy indicates low membrane fluidity. B DPH anisotropy of E. coli WT cells grown steady state at 30°C, 37°C or shifted from 30°C to 37°C followed by immediate measurement. In addition, DPH anisotropy of fabA(Ts) cells grown steady state at 30°C or shifted from 30°C to 37°C followed by measurement at the times indicated. D",
    "ncbi_link": "bkd: 938666///938672///938674///938677
fabA: 945568"
  },
  {
    "caption": "A Images of B. subtilis WT and Δbkd cells co-labelled with the membrane potential-sensitive dye DISC3(5) and the membrane permeability indicator Sytox Green. Membrane properties were assessed for Δbkd cells grown in the presence of MB, IB or washed precursor-free (IBPF) for the times indicated. As controls, WT cells were measured in the presence of depolarising antimicrobial peptide gramicidin ABC (gABC) or pore-forming lantibiotic Nisin. For cross-correlation between membrane depolarisation and membrane permeabilisation, see Appendix Fig S3A-C. B Quantification of DISC3(5) fluorescence for cells (n=100-142) depicted in panel A. Median represented by red line. C Images of E. coli WT and fabA(Ts) cells co-labelled with the same indicator dyes as in panel A. Membrane properties were assessed for fabA(Ts) at 30°C and upon transfer to non-permissive 37°C for the times indicated. As controls, WT cells were incubated with the pore-forming antibiotic Polymyxin B (PolyB). For cross-correlation between membrane depolarisation and membrane permeabilisation, see Appendix Fig S3D and E. The integrity of the diffusion barrier function was additionally studied via ONPG permeability in a ΔlacY background (see Fig EV1). D Quantification of DISC3(5) fluorescence for cells (n=76-141) depicted in panel C. Median represented by red line. Dat",
    "ncbi_link": "bkd: 938666///938672///938674///938677
fabA: 945568
lacY: 949083"
  },
  {
    "caption": "A Images of B. subtilis Δbkd cells stained with membrane dye FM 5-95 and expressing GFP fusions of DNA-binding protein HBsu (top), cell division protein FtsZ (middle) or cell elongation protein MreB (bottom). Cells were grown with IB or depleted for precursors for 90 min (IBPF). For further examples and additional time points, see Appendix Fig S4A. B Images of E. coli fabA(Ts) cells stained with FM 5-95 for the outer membrane and with DNA-intercalating dye DAPI (top), or expressing GFP sandwich (SW) fusions to the cell division protein FtsZ (middle) and the cell elongation protein MreB (bottom), respectively. Depicted are cells grown at 30°C or with a temperature shift to 37°C for 120 min. For a more detailed view on the influence of low membrane fluidity on membrane dissociation of RNase E as well as on the cell division machinery, see Figs EV2, EV3, EV4, and S5. For further examples and additional time points, see Appendix Fig S4B. D",
    "ncbi_link": "bkd: 938666///938672///938674///938677
fabA: 945568"
  },
  {
    "caption": "B Images of B. subtilis Δbkd cells grown with IB or without precursor (IBPF). Cells were stained with membrane fluidity-sensitive dye Laurdan and imaged at 460 nm, 520 nm and as the corresponding colour-coded Laurdan GP map. C Images of E. coli fabA(Ts) cells grown at 30°C or shifted to non-permissive 37°C for 120 min. Cells were stained and imaged as described in panel B. For a more pronounced view on domain formation associated with local differences in membrane fluidity, see Appendix Fig S7, showing E. coli fabA(Ts) grown in LB instead of M9 minimal medium with glucose/casamino acids. D Images of B. subtilis Δbkd cells grown and stained with Laurdan (imaged at 460 nm) as in panel B, but additionally expressing WALP23-mCherry. For corresponding fluorescence intensity correlation between images, see Appendix Fig S8A. Co-localisation of membrane dye FM 5-95 and transmembrane peptide WALP23 is shown in Appendix Figs S9 and S8C. E Images of E. coli fabA(Ts) cells grown and stained as in panel C, but additionally expressing WALP23-mScarlet-I. For corresponding fluorescence intensity correlation between images, see Appendix Fig S8B. Dat",
    "ncbi_link": "bkd: 938666///938672///938674///938677
fabA: 945568"
  },
  {
    "caption": "A Time lapse images of E. coli fabA(Ts) cells expressing FOF1 a-mNG. For corresponding controls, see Appendix Fig S10. Cells were grown at 30°C and shifted from 30°C to non-permissive 37°C. See Movie EV2 for full time lapse.",
    "ncbi_link": "fabA: 945568"
  },
  {
    "caption": "E Fatty acid composition of E. coli fabA(Ts) cells (same cell batch as in D) upon growth at 30°C, upon depletion of UFA by incubation at 37°C for 120 min and upon recovery by oleate supplementation for additional 120 min. For detailed analyses, see Appendix Fig S11B-D.",
    "ncbi_link": "fabA: 945568"
  },
  {
    "caption": "A Representative trajectory maps of individual FOF1 a-mNG molecules in E. coli WT and fabA(Ts) cells grown at 30°C and upon shift to non-permissive 37°C for 120 min. See Movie EV3 (WT) and Movie EV4 (fabA(Ts)) for accumulating trajectory maps of FOF1 a-mNG molecules.",
    "ncbi_link": "fabA: 945568"
  },
  {
    "caption": "Callus, de novo shoot, and root formation in wild-type (WT; Col), hag1-6, hag1-7, and 35S::FLAG:HAG1 hag1-7 root explants. Root explants were transferred onto CIM for 1 week (w) and then transferred onto fresh CIM, SIM, or RIM for callus, de novo shoot, or root induction, respectively. Scale bar: 1 cm. Graph on the right shows the percentage of explants with shoots formed as scored at 18 days (d) on SIM. 36 explants of each genotype were used for scoring.",
    "ncbi_link": "FLAG: 
hag1: 824626
HAG1: 824626"
  },
  {
    "caption": "Shoot regeneration assay using Col and hag1-6 root explants on media with different cytokinin (2IP) to auxin (IAA) ratios. Col and hag1-6 root explants derived from 20 seedlings were first incubated on CIM for 2 weeks and then transferred onto 150 mg/ml IAA-containing media supplemented with 0, 500, or 5,000 mg/ml 2IP. Pictures were taken at 27 d after transfer onto each media using representative explants. Scale bar: 2 mm.",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "Root explant-derived calli of Col and hag1-6 at 4 w on CIM (left). Scale bar: 1 mm. 4-w-old calli derived from 30 seedling roots of each genotype were collected to measure callus fresh weight (right).",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "Histochemical GUS staining of CYCB1;1:GUS in Col (left) and CYCB1;1:GUS in hag1-6. Shown are root explants at 4 d on CIM. Scale bar: 1 mm.",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "Statistic chart of differentially expressed genes (DEGs) in Col and hag1-6 roots (R), 4 d CIM-incubated root explants (C), 4 d CIM-incubated + 2 d SIM-incubated root explants (S), and 4 d CIM-incubated + 2 w SIM-incubated root explants (S2W). Green: up-regulated genes, log2 ratio ≥ 1; red: down-regulated genes, log2 ratio ≤ -1; FDR < 0.01.",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "pWOX5::GFP-ER expression in Col (WT) and hag1-6 explants on CIM and SIM. Time points selected for observation are indicated. Cellular outlines were visualized with propidium iodide (PI) staining (red).",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "pSCR::GFP-ER expression in Col (WT) and hag1-6 explants on CIM and SIM. Time points selected for observation are indicated. Cellular outlines were visualized with PI staining (red).",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "pSCR::GFP-ER expression in Col (WT) and hag1-6 root tips at various time points on CIM. Time points selected for observation are indicated. Cellular outlines were visualized with PI staining (red).",
    "ncbi_link": "hag1: 824626"
  },
  {
    "caption": "WOX5 transcript levels in Col and hag1-6 hypocotyl (D) and cotyledon (E) explants at indicated days on CIM.",
    "ncbi_link": "hag1: 824626
WOX5: 820297"
  },
  {
    "caption": "SCR transcript levels in Col and hag1-6 hypocotyl (F) and cotyledon (G) explants at indicated days on CIM.",
    "ncbi_link": "hag1: 824626
SCR: 824589"
  },
  {
    "caption": "H3Ac enrichment at the WOX5 (A), SCR (B), PLT1 (C), and PLT2 (D) loci in Col (upper black diagram) and hag1-6 (lower red diagram) calli (1 w CIM) as determined by ChIP seq. p-value cutoff for peak detection using MACS2 was 5e-2 for WOX5 (A) and 1e-5 for SCR (B), PLT1 (C), and PLT2 (D). ChIP-seq data were visualized using Integrated Genome Browser (IGB; http://bioviz.org/igb/index.html). The X and Y axis represent the genomic position of the corresponding gene and the number of overlapping reads per base pair position, respectively. Schematic representation of each locus is depicted at the bottom. Exons are indicated as boxes whereas intergenic sequences and introns are marked with lines. 5' and 3' UTRs are represented as gray boxes. Transcription start sites are indicated with arrows.",
    "ncbi_link": "hag1: 824626
PLT1: 821632
PLT2: 841542
SCR: 824589
WOX5: 820297"
  },
  {
    "caption": "ChIP-qPCR analysis of H3Ac levels at the WOX5 (E), SCR (F), PLT1 (G), and PLT2 (H) loci in Col and hag1-6. Root (R), 1 w CIM (C), and 1 w CIM + 2 w SIM (S) samples were used for assays.",
    "ncbi_link": "hag1: 824626
PLT1: 821632
PLT2: 841542
SCR: 824589
WOX5: 820297"
  },
  {
    "caption": "Direct targeting of HAG1:HA protein to WOX5 (I), SCR (J), PLT1 (K), and PLT2 (L) chromatin as determined by ChIP-qPCR.",
    "ncbi_link": "PLT1: 821632
PLT2: 841542
SCR: 824589
WOX5: 820297"
  },
  {
    "caption": "Transcript levels of WOX7 (A) and WOX14 (B) in Col and hag1-6 roots (R), 4 d CIM explants (C), 4 d CIM + 2 d SIM explants (S), and 4 d CIM + 2 w SIM explants (S2W). Levels of Col R were set to 1 after normalization with UBQ10.",
    "ncbi_link": "UBQ10: 
hag1: 824626
WOX14: 838660
WOX7: 830462"
  },
  {
    "caption": "De novo shoot regeneration of Col, Nossen (No), wox5-3, wox7-1, wox14-1, and wox5-3 wox7-1 wox14-1 root explants. Col is the WT control for wox5-3 and wox7-1, whereas No is the WT control for wox14-1. The picture was taken at 3 w on SIM using representative explants of each genotype. Scale bar: 1 cm. Percentage of explants with shoots was scored at indicated weeks on SIM (D).",
    "ncbi_link": "wox14: 838660
wox5: 820297
wox7: 830462"
  },
  {
    "caption": "H3Ac enrichment at the WOX14 locus in Col (upper black diagram) or hag1-6 (lower red diagram) calli as determined by ChIP seq. p-value cutoff for peak detection using MACS2 was 1e-5. See Figs 3A-D for schematic.",
    "ncbi_link": "hag1: 824626
WOX14: 838660"
  },
  {
    "caption": "ChIP-qPCR analysis of H3Ac levels at the WOX14 locus of Col and hag1-6. Regions tested are indicated in the schematic in (E). Sample preparation and data presentation were performed as described in Figs 3E-H.",
    "ncbi_link": "hag1: 824626
WOX14: 838660"
  },
  {
    "caption": "Direct targeting of HAG1:HA protein to WOX14 chromatin as determined by ChIP-qPCR.",
    "ncbi_link": "WOX14: 838660"
  },
  {
    "caption": "De novo shoot regeneration using Col and scr mutants; scr-3 (A and B) and scr-6 (A and C). Explants with shoots were scored at indicated days on SIM using Col and scr-3 root explants that had been pre-incubated on CIM for 2 w (B) or Col and scr-6 hypocotyl explants that had been pre-incubated on CIM for 1 w (C). Scale bar: 1 mm.",
    "ncbi_link": "scr: 824589"
  },
  {
    "caption": "De novo shoot regeneration of Col, wox5-3, scr-3, and wox5-3 scr-3. The percentage of root explants with shoots (E) and the number of shoots per root explant (F) were scored at 15 d on SIM. The explants had been pre-incubated on CIM for 2 w before transfer onto SIM. Scale bar: 1 cm.",
    "ncbi_link": "scr: 824589
wox5: 820297"
  },
  {
    "caption": "Transcript levels of PLT1 (G) and PLT2 (H) in Col, wox5-3, scr-3, and wox5-3 scr-3 roots (R), 1 w CIM explants (C), and 1 w CIM + 2 w SIM explants (S2W) as determined by RT-qPCR. Levels of Col R were set to 1 after normalization with UBQ10.",
    "ncbi_link": "UBQ10: 
PLT1: 821632
PLT2: 841542
scr: 824589
wox5: 820297"
  },
  {
    "caption": "Activation of WOX5 by DEX treatment of 35S::GVG-WOX5 in Col and hag1-6. Root explants of 35S::GVG-WOX5 and 35S::GVG-WOX5 hag1-6 were transferred onto the indicated combinations of CIM and SIM supplemented with or without 20 μM DEX. DEX was treated for 3-d-pulse period on CIM or/and SIM (see Materials and Methods for details and Appendix Fig S11A for schematics of the experimental procedure). Morphology of shoots regenerated from 35S::GVG-WOX5 and 35S::GVG-WOX5 hag1-6 root explants (A). Explants with shoots were scored at 3 w after transfer onto SIM with or without DEX (B).",
    "ncbi_link": "GVG: 
hag1: 824626
WOX5: 820297"
  },
  {
    "caption": "Activation of SCR by DEX treatment of UBI::mCHERRY-GR-SCR in Col and hag1-6.",
    "ncbi_link": "mCHERRY: 
UBI: 
hag1: 824626
SCR: 824589"
  },
  {
    "caption": "Activation of WOX5 and SCR by DEX treatment of 35S::GVG-WOX5 UBI::mCHERRY-GR-SCR in Col and hag1-6.",
    "ncbi_link": "GVG: 
mCHERRY: 
hag1: 824626
SCR: 824589
WOX5: 820297"
  },
  {
    "caption": "Comparison of constitutively active rhodopsin mutants M257Y6.40 (left [21]), T94I2.61 (middle) and G90D2.57 (right [16]). All-trans (yellow) and cis retinal isomers (orange), the side of retinal attachment K2967.43 (blue slate), the retinal counterion E1133.28 (blue slate), GαCT peptides (cyan) and the constitutively activating mutations M257Y6.40, T94I2.61, and G90D2.57 (green) are shown as spheres. Palmitoylation at C323H8 and glycosylation at N15NT are shown as sticks. The lower panels compare the M257Y6.40, T94I2.61 and G90D2.57 retinal-binding pockets. All constructs also contain an additional thermostabilizing disulfide bridge, depicted as (c-c), to enhance the stability [18] and crystallizability [19] without changing the rhodopsin activation pathway [20].",
    "ncbi_link": "rhodopsin: 6010"
  },
  {
    "caption": "Kinetic characterization of the rhodopsin dark state. Thermal decay of dark state rhodopsin: A) WT, B) T94I and C) G90D rhodopsin. The spectra are normalized to the OD280 and OD500/OD480 at t=0. D) Absorption maximum plotted as a function of time and fitted to a single exponential decay.",
    "ncbi_link": "rhodopsin: 6010"
  },
  {
    "caption": "Retinal isomerization in the rhodopsin dark state: E) WT, F) T94I and G) G90D rhodopsin, H) The fraction of 11-cis retinal is plotted as a function of time and fitted to a single exponential decay.",
    "ncbi_link": "rhodopsin: 6010"
  },
  {
    "caption": "SB stability in dark state rhodopsin: I) WT, J) T94I and K) G90D rhodopsin. L) OD440 is plotted as a function of time and fitted to a single exponential decay. All decay rates were measured at 55 C.",
    "ncbi_link": "rhodopsin: 6010"
  },
  {
    "caption": "(b,c) Effects of miR-212 and miR-132 precursors and inhibitors (anti) on cardiomyocyte cell size as compared with the effects of scrambled (Scr) controls (n=5-13). Representative images used for quantification of cardiomyocyte cell size are shown in c.",
    "ncbi_link": "miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(d) Effects of various pro-hypertrophic stimuli on miR-212 and miR-132 expression in neonatal cardiomyocytes (n=6-10).",
    "ncbi_link": "miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(e) miR-212 and miR-132 expression levels during pressure-induced left ventricular hypertrophy 3 and 21 days after transaortic constriction (TAC) surgery of mice (n=4).",
    "ncbi_link": "miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(g,h) miR-212 and miR-132 expression (normalized to sno-202 levels) in fractionated cardiomyocytes and cardiac fibroblasts derived from adult mice after 3 and 35 days of TAC. All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005. Scale bar in c represents 50 μm. ACTN2, α-cardiac actinin; Ang II, angiotensin-2; a.u., arbitrary unit; d, day; DAPI, 4′,6-diamidino-2-phenylindole; FC, fold change; NS, no significant difference; P/I, phenylephrine/isoprenaline.",
    "ncbi_link": "sno-202: 
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(b) Expression levels of miR-212 and miR-132 in heart samples of individual wild-type (WT) and miR-212/132 transgenic (TG) mice as assayed by RT-PCR analysis against the mature forms of corresponding microRNAs. Rnu6b was used as housekeeping control.",
    "ncbi_link": "Rnu6b: 
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(c) Survival rate of two different miR-212/132 TG mouse families (TG-Fam23, TG-Fam43) versus WT controls was analysed by Kaplan-Meier survival assay (n=87, 65 and 53 for WT, TG-Fam23 and TG-Fam43, respectively).",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(e,f) Heart-to-body-weight ratios (e) and cardiomyocyte diameter (f) in 8-week-old α-MHC-miR-212/132 transgenic mice compared with their wild-type littermates (n=5-7). Scale bar, 50 μm.",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(g-i) Echocardiography analysis of cardiac dimensions and function for α-MHC-miR-212/132 TG mice and WT controls (n=16-18) (g) end-systolic area, (h) end-diastolic area, (i) fractional shortening. All values in e-i represent mean±s.e.m. *P0.05; **P0.01; ***P0.005. DAPI, 4′,6-diamidino-2-phenylindole; WGA, wheat germ agglutinin (membrane stain).",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(a) Heart-to-body-weight ratios for 12-week-old miR-212/132 null (KO) and wild-type (WT) mice (n=5-6).",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(b) Cardiomyocyte cell size of neonatal miR-212/132 null and WT mice (n=5-6 isolations).",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(c-f) Heart-to-body-weight ratios (c) in Sham-operated WT mice and miR-212/132 null and WT mice3 weeks after TAC surgery (n=4-7). Scale bar, 50 μm.",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(c-f) cardiomyocyte diameter (d), cardiac fibrosis (e) in Sham-operated WT mice and miR-212/132 null and WT mice3 weeks after TAC surgery (n=4-7). Scale bar, 50 μm.",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(c-f) lung wet weight (f) in Sham-operated WT mice and miR-212/132 null and WT mice 3 weeks after TAC surgery (n=4-7). Scale bar, 50 μm.",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(g-i) Echocardiography analysis of cardiac dimensions and function in Sham-operated WT mice and miR-212/132 null and WT mice 3 weeks after TAC (n=4-11). (g) End-diastolic area, (h) end-systolic area and (i) fractional shortening. All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005; #P0.05 compared with WT TAC; ###P0.005 compared with WT TAC; PSR, picrosirius red (collagen stain). DAPI, 4′,6-diamidino-2-phenylindole; WGA, wheat germ agglutinin.",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(a) Luciferase activity levels upon cotransfection of a luciferase construct containing wild-type (WT) or mutated (Mut.) 3′UTR of FoxO3 with scrambled (Scr) control (Ctrl), pre-miR-132 or pre-miR-212 (n=9).",
    "ncbi_link": "luciferase: 
FoxO3: 56484
miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(b,c) Expression levels of FoxO3 on mRNA (b) and protein levels (c) in hearts of WT and α-MHC-miR-212/-132 transgenic (TG) mice. M: Size marker (n=9-13).",
    "ncbi_link": "FoxO3: 56484
miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(d) FoxO3 mRNA levels in neonatal rat cardiomyocytes transfected with Scr Ctrl, anti-miR-212 and anti-miR-132 after phenylephrine (PE, 10 μM) treatment (n=6-9; P-values against Scr+PE).",
    "ncbi_link": "FoxO3: 294515
miR-132: 100314029
miR-212: 100314247"
  },
  {
    "caption": "(e-g) Expression levels of atrogin-1 (e) and Mcip1 (f) and calcineurin phosphatase activity levels (g) in hearts of WT and α-MHC-miR-212/132 TG mice (n=5-9).",
    "ncbi_link": "atrogin-1: 67731
miR-212: 387208
α-MHC: 17888
Mcip1: 54720"
  },
  {
    "caption": "(h) Luciferase activity levels showing the NFAT transcriptional activity in cardiomyocytes transfected with Scr Ctrl, pre-miR-132 or pre-miR-212 (n=5).",
    "ncbi_link": "miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "(i,j) Mcip1.4 (i) and atrogin-1 (j) mRNA levels in WT and miR-212/132 null (KO) mice 3 weeks after transaortic constriction (TAC) or Sham operation (n=5-7 per group). All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005. #P0.05 compared with WT TAC. FC, fold change.",
    "ncbi_link": "atrogin-1: 67731
miR-212: 387208
Mcip1: 54720"
  },
  {
    "caption": "(a) mRNA expression levels of autophagic marker genes in hearts of wild-type (WT) and α-MHC-miR-212/132 transgenic (TG) mice (n=9-10).",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(b,c) Ratio of LC3II to LC3I (b) and p62 protein levels (c) in WT, miR-212/132 null (KO) and α-MHC miR-212/132 TG mice. M: Size marker (n=4-12).",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(d,e) Representative images (d) and quantification (e) of LC3:mCherry puncta (in red) in control and miR-212/132-overexpressing TG H9c2 cells under normal and serum/glucose-deprivation conditions (n=30). Nuclei are stained in blue with Hoechst33342.",
    "ncbi_link": "miR-212: 100314247"
  },
  {
    "caption": "(f,g) Representative electron microscopy images (f) and quantification (g) of autophagic vacuoles in control and miR-212/132-overexpressing TG H9c2 cells under normal and serum/glucose-deprivation conditions (n=20).",
    "ncbi_link": "miR-212: 100314247"
  },
  {
    "caption": "(h,i) Representative FACS plots (h) and quantification (i) of percent increase of autophagic flux in control and miR-212/132-overexpressing TG H9c2 cells under normal and serum/glucose-deprivation conditions (n=3-4 experiments). All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005. Scale bars, 50 μm in d and 2 μm in f. FC, fold change.",
    "ncbi_link": "miR-212: 100314247"
  },
  {
    "caption": "(b) LC3II to LC3I ratios in wild-type (WT) mice fed with normal diet and WT, miR-212/132−/− null and α-MHC miR-212/132 transgenic (TG) mice under starvation for 31 h (n=4).",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(c) Electron microscopy from ultrathin sections of resin-embedded heart biopsies of fed and starved WT, miR-212/132 null (KO) and cardiomyocyte-specific miR-212/132-overexpressing (TG) mice. White spots around the mitochondria (dark grey structures) are autophagic vacuoles. The electron-dense black spots shown with white arrows are autophagosomes. Scale bars, 4 μm.",
    "ncbi_link": "miR-212: 387208"
  },
  {
    "caption": "(d) p-mTOR/mTOR ratios in WT and miR-212/132 TG H9c2 cells 24 h after normal and starvation (serum/glucose-deprived) conditions (n=6).",
    "ncbi_link": "miR-212: 100314247"
  },
  {
    "caption": "(e) p-mTOR/mTOR ratios in hearts of WT and α-MHC miR-212/132 TG mice fed with normal diet or 31 h after starvation (n=4). M, size marker. All values represent mean±s.e.m. **P0.01; ***P0.005; #P=0.11.",
    "ncbi_link": "miR-212: 387208
α-MHC: 17888"
  },
  {
    "caption": "(a-c) Heart-to-body-weight ratios (a), cardiomyocyte diameters (b) and cardiac fibrosis (c) in Sham-operated mice and mice treated with intravenous injection of either scrambled control (Scr) or miR-132 inhibitors (Ant-132) after TAC. These mice were analysed 3 weeks after TAC (n=4-11). PSR, picrosirius red staining.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "(d-f) Echocardiography analysis of cardiac dimensions and function in Sham-operated mice and mice treated with intravenous injection of either control (Scr) or miR-132 inhibitors (Ant-132) after TAC. These mice were analysed 3 weeks after TAC for (d) fractional shortening, (e) end-diastolic area and (f) end-systolic area (n=4-9).",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "(g-i) Cardiac FoxO3 protein levels in mice treated with intravenous injection of either control (Scr) or miR-132 inhibitors (Ant-132) 3 weeks after TAC and treatment (n=4-8). M: size marker. All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005; #P0.05 against TAC-control; ##P0.01 against TAC-control; ###P0.005 against TAC-control. Scale bars, 50 μm. DAPI, 4′,6-diamidino-2-phenylindole; FC, fold change; WGA, wheat germ agglutinin.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "(g-i) calcineurin activity (h) and Mcip1.4 mRNA levels (i) in mice treated with intravenous injection of either control (Scr) or miR-132 inhibitors (Ant-132) 3 weeks after TAC and treatment (n=4-8). M: size marker. All values represent mean±s.e.m. *P0.05; **P0.01; ***P0.005; #P0.05 against TAC-control; ##P0.01 against TAC-control; ###P0.005 against TAC-control. Scale bars, 50 μm. DAPI, 4′,6-diamidino-2-phenylindole; FC, fold change; WGA, wheat germ agglutinin.",
    "ncbi_link": "miR-132: 387150
Mcip1.4: 54720"
  },
  {
    "caption": "B Trans-activation activity assays of CDF4 in Arabidopsis protoplasts. The full-length ORF of CDF4 and its four deletion constructs Dof (gray boxes) represent the DNA-binding domains of CDF4. Negative control was the effector vector without gene inserts. The effector vector used is shown in the left panel. The GAL4 transient expression assays were performed using Arabidopsis protoplasts, shown in the right panel. Deletion of the CDF4 N-terminal domain compromised the transcriptional repression by CDF4 in our assay. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "C Localized expression of CDF4 in a senescing rosette leaf. The ~50% senesced rosette leaf was cut into three parts as indicated by the red lines. The level of CDF4 mRNA was determined in the three sections of the senescing leaf. Base; Middle; Tip. Three independent experiments were conducted. Values are given as mean ± SD, n=3.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "D CDF4 expression level at various developmental stages of rosette leaves. YL, young leaf; NS, fully expanded, non-senescent leaf; ES, early-senescent leaf, with 1/4 leaf area turned yellow; LS, late-senescent leaf, with >50% leaf area turned yellow. Three independent experiments were conducted. Values are given as mean ± SD, n=3.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "E Effect of plant growth hormones (1 mM SA, 1 μM ABA, 10 μM JA and 10 μM 1-aminocyclopropane -1-carboxylic acid (ACC) on CDF4 expression. Three independent experiments were conducted. Values are given as mean ± SD, n=3.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "F Effects of abiotic stress treatments on CDF4 expression. Rosette leaves were treated with salt (100 mM NaCl), drought, H2O2 (2mM) or darkness. Three independent experiments were conducted. Values are given as mean ± SD, n=3.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "G Effects of SA, H2O2, and dark treatment on CDF4 expression in the aba2-1 mutant background. AtACT2 was used as an internal control. Three independent experiments were conducted. Values are given as mean ± SD, n=3.",
    "ncbi_link": "aba2: 841665
ACT2: 821411
CDF4: 817975"
  },
  {
    "caption": "A The age-dependent leaf senescence symptoms in the vector control and 35S::CDF4 lines grown under long-day conditions were shown at 21-days-old. The 35S::CDF4 plants had a small leaf size and extremely early leaf senescent phenotype, while the control vector leaves were fully green. Scale bars indicate 1 cm.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "B The increase in SAG12, SAG13, PR1 and PR5 gene expression levels were investigated in 35S::CDF4 plants. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 in comparison with the vector control by Student's t test.",
    "ncbi_link": "CDF4: 817975
PR1: 815949
PR5: 843842
SAG12: 834629
SAG13: 817484"
  },
  {
    "caption": "C Phenotypes of vector control, pER8::CDF4, pER8::CDF4-RNAi and pER8::amiCDF4 plants, after treatment with 20 µM estradiol for seven days at 18-days-old. Scale bars indicate 1.5 cm.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "E Analysis of the relative chlorophyll concentration in the sixth and seventh rosette leaves from the vector control, pER8::CDF4, pER8::CDF4-RNAi and pER8::amiCDF4 lines shown at various development stages. Four independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "D The leaf senescence phenotypes of detached rosette leaves in vector control, pER8::CDF4, pER8::CDF4 -RNAi and pER8::amiCDF4 lines before and after treatment with 2 mΜ H2O2 in the dark for four days. Scale bars indicate 0.7 cm.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "A Measurement of free ABA levels in the third and fourth rosette leaves from 21-day-old transgenic lines with altered CDF4 expression after estradiol induction for three days (once every day). Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "B, C qPCR analysis of ABA synthesis and signaling-related genes in Col-0 and 35S::CDF4 plants. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t-test.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "D, E Relative expression of NCED2 and NCED3 in 14-day-old CDF4GR transgenic plants treated with 20 μM β-estradiol or mock treatment for 0, 2, or 4 h. The expression of the corresponding genes in mock-treated plants was set to 1.0. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975
NCED2: 827562
NCED3: 820667"
  },
  {
    "caption": "F, G Relative expression level of NCED2 and NCED3 in 14-day-old CDF4GR transgenic plants treated with 20 μM DEX, 100μM CHX, DEX plus 100μM CHX, or mock. The gene expression in mock-treated plants was set to 1.0. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975
NCED2: 827562
NCED3: 820667"
  },
  {
    "caption": "H Schematic diagram indicating the locations of six DOF motif clusters (D1 to D6) in the NCED2 and NCED3 gene promoters. I ChIP-qPCR analysis of the ability of CDF4 to bind to the promoters of NCED2 and NCED3. An anti-HA monoclonal antibody was used for DNA immunoprecipitation from three-week-old pER8::CDF4-HA transgenic plants. Black bars indicate the enrichment fold-changes normalized to that of ACT2. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t-test. Transient dual-luciferase reporter assay. The pGreenII-0800 LUC construct containing the CDF4 promoter and the p62-SK construct with or without the CDF4 coding region and CDF4-VP16 were transiently co-transformed into Col-0 protoplasts. Firefly luciferase (LUC) and Renilla luciferase (REN) activities were measured after culturing the protoplasts under low light conditions for 16 h. The ProNCED2/3:LUC /Pro35S:REN ratio represents the relative activities of NCED2 and NCED3 transcription. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t-test.",
    "ncbi_link": "HA: 
LUC: 
luciferase: 
p62: 
ACT2: 821411
CDF4: 817975
NCED2: 827562
NCED3: 820667"
  },
  {
    "caption": "K Transient dual-luciferase reporter assay. The pGreenII-0800 LUC construct containing the CDF4 promoter and the p62-SK construct with or without the CDF4 coding region and CDF4-VP16 were transiently co-transformed into Col-0 protoplasts. Firefly luciferase (LUC) and Renilla luciferase (REN) activities were measured after culturing the protoplasts under low light conditions for 16 h. The ProNCED2/3:LUC /Pro35S:REN ratio represents the relative activities of NCED2 and NCED3 transcription. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t-test.",
    "ncbi_link": "LUC: 
luciferase: 
p62: 
CDF4: 817975
NCED2: 827562
NCED3: 820667"
  },
  {
    "caption": "A-D Transcript levels were determined by qPCR and normalized to AtACT2. (A, C) Localized NCED2 and NCED3 expression in the wild-type senescing leaf. Half-senesced leaves were split into three parts, as shown in Fig. 1A, C. (B, D) NCED2 and NCED3 expression during leaf senescence in the vector control and CDF4- RNAi-1 plants. Transgenic plant leaves were analyzed from 7 to 56 d (d, days after planting). Four independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t-test.",
    "ncbi_link": "ACT2: 821411
CDF4: 817975
NCED2: 827562
NCED3: 820667"
  },
  {
    "caption": "E Observation of rosette leaf longevity from the 26-day-old vector control, pER8::CDF4, pER8::CDF4 & nced2, pER8::CDF4 & nced3 and pER8::CDF4 & nced2nced3 transgenic plants after 20 μM estradiol induction for two weeks. Phenotype of detached rosette leaves arranged from oldest to youngest. Scale bars indicate 1.5 cm.",
    "ncbi_link": "CDF4: 817975
nced2: 827562
nced3: 820667"
  },
  {
    "caption": "(F) SAG12 expression level in rosette leaves at various development stages. Three independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t-test.",
    "ncbi_link": "SAG12: 834629"
  },
  {
    "caption": "A The senescence phenotype of the vector control, pER8::CDF4 and pER8::CDF4::RNAi detached leaves treated with H2O2 and incubated in the dark for three days. The third leaf in rosettes of 3-week-old plants was detached and incubated in MES buffer (2 mM MES, pH 5.8) treated with 2 mM H2O2 and 20 μM β-estradiol under dark conditions for three days. Picture shows the leaves before and after treatment. Scale bars indicate 1 cm.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "A Measurement of catalase activity in vector control and CDF4RNAi plants. Ten-day-old green seedlings ("Young") and the third and fourth rosette leaves from 36-day-old plants ("Old") were used, respectively. Three independent experiments were conducted. Data are represented as means ± SD, n=3. Student's t test, *p<0.05.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "D ChIP-qPCR analysis of the relative binding of CDF4 to the promoter of CAT2. An anti-HA monoclonal antibody was used for DNA immunoprecipitation from 32-d-old pER8::CDF4-HA transgenic plants. Black columns indicate the enrichment fold-changes normalized to that of ACT2. Three independent experiments were conducted. Data are represented as means ± SD, n=3. Student's t test, *p<0.05.",
    "ncbi_link": "HA: 
ACT2: 821411
CDF4: 817975
CAT2: 829661"
  },
  {
    "caption": "E Transient dual-luciferase reporter assay. The pGreenII-0800 LUC construct containing the CAT2 promoter and the p62-SK construct with or without CDF4 were transiently co-transformed into Col-0 protoplasts. Firefly luciferase (LUC) and Renilla luciferase (REN) activity were measured after culturing the protoplasts under low light conditions for 16 h. six independent experiments were conducted. Values are given as mean ± SD, n=6. *p<0.05 by Student's t test.",
    "ncbi_link": "LUC: 
luciferase: 
p62: 
CDF4: 817975
CAT2: 829661"
  },
  {
    "caption": "A The senescence phenotypes of five-week-old vector control, proSAG12::CDF4 and proSAG12::CDF4 & 35S::CAT2 plants, from old to young. Scale bars indicate 1.5 cm.",
    "ncbi_link": "CDF4: 817975
CAT2: 829661
SAG12: 834629"
  },
  {
    "caption": "B qPCR analysis of the expression of CDF4 and CAT2 in the leaves Four independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t test.",
    "ncbi_link": "CDF4: 817975
CAT2: 829661"
  },
  {
    "caption": "qPCR analysis of the expression of CAT2 in the leaves Four independent experiments were conducted. Values are given as mean ± SD, n=4. *p<0.05 by Student's t test.",
    "ncbi_link": "CAT2: 829661"
  },
  {
    "caption": "(A) Observation of inflorescences of 7-week-old wild-type (WT) Arabidopsis and the CDF4 transgenic plants. The asterisk represents the flower organ attached along the inflorescence. Scale bar indicates 1.5 cm.",
    "ncbi_link": "CDF4: 817975"
  },
  {
    "caption": "Selected abscission-related gene expression levels in (B) WT and proIDA::CDF4 lines by using qPCR analysis. The expression of these selected genes in the wild-type plant is given as 1. The relative expression level represents only the level of expression of the gene relative to the wild type. ACTIN2 was used as the internal control. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "ACTIN2: 821411
CDF4: 817975
IDA: 843208"
  },
  {
    "caption": "Selected abscission-related gene expression levels in (C) WT and proIDA::CDF4RNAi lines by using qPCR analysis. The expression of these selected genes in the wild-type plant is given as 1. The relative expression level represents only the level of expression of the gene relative to the wild type. ACTIN2 was used as the internal control. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "ACTIN2: 821411
CDF4: 817975
IDA: 843208"
  },
  {
    "caption": "E Observation of GUS staining activity in the proPGAZAT::GUS and proPGAZAT::GUS & proIDA::CDF4. Scale bar indicates 0.5 cm.",
    "ncbi_link": "GUS: 
CDF4: 817975
IDA: 843208"
  },
  {
    "caption": "F ChIP-qPCR analysis of the relative binding of CDF4 to the promoter regions of PGAZAT. An anti-HA monoclonal antibody was used for DNA immunoprecipitation from 6-week-old pER8::CDF4-HA transgenic plants after estradiol induction. Black columns indicate the enrichment fold changes normalized to ACT2. Three independent experiments were conducted. Values are given as mean ± SD, n=3. *p<0.05 by Student's t test.",
    "ncbi_link": "HA: 
ACT2: 821411
CDF4: 817975
PGAZAT: 818785"
  },
  {
    "caption": "A. Histograms of spindle angle of GFP-H2B U2OS cells transfected with either GAPDH or Spindly siRNA and filmed on rectangular micropatterns. Cells were filmed 48 hours post-transfection.",
    "ncbi_link": "GAPDH: 2597
Spindly: 54908"
  },
  {
    "caption": "B. Mitotic timing of control-depleted U2OS cells or CLIP-170-depleted cells. CLIP-170-depeleted cells are split in two categories; 'aligned' and 'misaligned', relating to the observed chromosome misalignment phenotype",
    "ncbi_link": "CLIP-170: 6249"
  },
  {
    "caption": "C. The histograms of spindle angles for the two different categories of CLIP-170-depleted U2OS cells (Left graph with alignment defect, right graph without alignment defect).",
    "ncbi_link": "CLIP-170: 6249"
  },
  {
    "caption": "D and E. Mitotic timing and spindle angle histograms of control (GAPDH)-depleted U2OS cells and CENP-E-depleted cells.",
    "ncbi_link": "CENP-E: 1062
GAPDH: 2597"
  },
  {
    "caption": "A. HeLa cell stably expressing GFP-LGN and transiently expressing RFP-H2B was treated with noscapine to induce chromosome misalignments. Cells were imaged every 5 minutes. The time is relative to NEB. The red arrows indicate cortical regions where the chromosomes are in close proximity to the cell boundaries, accompanied by the displacement of LGN from the cortex.",
    "ncbi_link": "LGN: 29899
H2B: 8349"
  },
  {
    "caption": "B. Similar assay as described in supplementary figure 2D was carried out in the presence of a small molecule inhibitor against Aurora-B (ZM447439) in combination with the proteasome inhibitor MG-132 to keep cells arrested in mitosis and in B. with an inhibitor against Plk1 (BI2536). Drugs were added at the same timing as Hoechst, 30 minutes prior to imaging.",
    "ncbi_link": "Plk1: 5347"
  },
  {
    "caption": "A. Immunofluorescence images and quantifications of KT-localized Plk1 in U2OS cells after PBIP1 depletion. Cells were either Mock transfected or with PBIP1 siRNA for 72 hours. Cells were treated with nocodazole for 1 hour and fixed. Cells were stained with the centromere marker ACA, Plk1 and DAPI.",
    "ncbi_link": "PBIP1: 79682"
  },
  {
    "caption": "B. Representative images and histograms showing the effect of chromosome position on cortical LGN enrichment after 72 hours of Mock and PBIP1 depletion.",
    "ncbi_link": "PBIP1: 79682"
  },
  {
    "caption": "C. Live cellimages and histograms of GFP-H2B U2OS cells Mock transfected or with siPBIP1 filmed on rectangular micropatterns in the presence of a CENP-E inhibitor. The spindle angles for both conditions were scored at 32 minutes after NEB.",
    "ncbi_link": "CENP-E: 1062
PBIP1: 79682
H2B: 8349"
  },
  {
    "caption": "E) Barplots showing qRT-PCR gene expression levels (mean +/- S.D.) of PTEN, FNDC3B, and STAM genes in control, 4hr and 24hr actinomycin D treated K562 cells. p-value: two-tailed t-test, (*** p < 0.05). The results represent data from 3 technical replicates from 3 independent biological preparations.",
    "ncbi_link": "FNDC3B: 64778
PTEN: 5728
STAM: 8027"
  },
  {
    "caption": "F) Gene expression analysis by RT-qPCR of CrizR1 cells treated with the indicated concentrations of bemcentinib for 48h. LOX: P=0.03; SNAI2: P =0.02; VIM: P =0.03.",
    "ncbi_link": "LOX: 4015
SNAI2: 6591
VIM: 7431"
  },
  {
    "caption": "D) (Top) Western blot analysis of CrizR1 cells treated with siScrambled or siRNA for CDK7 or CDK9 for 72h. (Bottom) CrizR1 were treated as above, or with DMSO/alvocidib/THZ1 and cells were stained with Annexin V/PI and analysed by flow cytometry for Annexin V+ cells 72h post-transfection (n=2). Annexin siCDK7 P=0.2, siCDK9 P=0.015, alvocidib P=0.0001, THZ1 P =0.004.",
    "ncbi_link": "CDK7: 1022
CDK9: 1025"
  },
  {
    "caption": "E) H3122 parental and CrizR1 cells were treated with DMSO, 200nM alvocidib or 250ng/ml actinomycin D for 6 hours. RNA was extracted and the mRNA levels of the indicated genes were quantified by RT-qPCR. CDK1: DMSO vs H3122 DMSO P=0.002, Actinomycin vs DMSO P=0.0003, Alvocidib vs DMSO P=0.0005; CDK2: DMSO vs H3122 DMSO P =0.0001, Actinomycin vs DMSO P<0.0001, Alvocidib vs DMSO P=0.0005; CDK6: DMSO vs H3122 DMSO P =0.0005, Actinomycin vs DMSO P =0.0004, Alvocidib vs DMSO P =0.0004; CDK9: DMSO vs H3122 DMSO P=0.0003, Actinomycin vs DMSO P =0.0002, Alvocidib vs DMSO P =0.0003; CCNB1: DMSO vs H3122 DMSO P=0.02, Actinomycin vs DMSO P=0.0002, Alvocidib vs DMSO P=0.0003; CCNE1: DMSO vs H3122 DMSO P =0.0004, Actinomycin vs DMSO P =0.0004, Alvocidib vs DMSO",
    "ncbi_link": "CCNB1: 891
CCNE1: 898
CDK1: 983
CDK2: 1017
CDK6: 1021
CDK9: 1025"
  },
  {
    "caption": "F) RT-qPCR analysis of MCL-1 and Survivin expression after treatment of CrizR1 cells with 100nM alvocidib, 25nM dinaciclib and 50 nM THZ1. RNA was extracted after 24h of treatment. MCL-1 alvocidib vs control P=0.0001, dinaciclib vs control P=0.0001, THZ1 vs control P =0.0001; Survivin: alvocidib vs control P =0.01, dinaciclib vs control P=0.01, THZ1 vs control P =0.0001.",
    "ncbi_link": "Survivin: 332
MCL-1: 4170"
  },
  {
    "caption": "G) (Top) Western blot analysis of CrizR1 cells treated with siScrambled or with a pool of 4 different siRNAs targeting Survivin (siBIRC5). (Bottom) Cells were stained with Annexin V/PI and analysed by flow cytometry for Annexin V+ cells 72h post-transfection. Annexin: early apoptosis P =0.0003, late apoptosis P =0.5, alive P <0.0001.",
    "ncbi_link": "Survivin: 332
BIRC5: 332"
  },
  {
    "caption": "H) The CCLE RNA-seq dataset was used and RPKM values were plotted for the Cyclin D1 and Survivn genes, indicating high expression in H3122 cells compared with other LUAD cells.",
    "ncbi_link": "Survivn: 332
Cyclin D1: 595"
  },
  {
    "caption": "D) Gene tracks of RNA polymerase II occupancy at the MCL1, BIRC5 (Survivin), CCND1 and MYC genes.",
    "ncbi_link": "BIRC5: 332
Survivin: 332
CCND1: 595
MCL1: 4170
MYC: 4609"
  },
  {
    "caption": "E) qPCR of MYC and CCND1 upon treatment of CrizR1 cells with Alvocidib or THZ1 for 6h. The graph represents the mean fold change ± SD. MYC: alvocidib vs DMSO P =0.03, THZ1 vs DMSO P <0.0001; CCND1: alvocidib vs DMSO P =0.001, THZ1 vs DMSO P =0.003.",
    "ncbi_link": "CCND1: 595
MYC: 4609"
  },
  {
    "caption": "F) BIM is upregulated upon MYC silencing in CrizR1 cells.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "G) Annexin V assay showing the percentage of apoptotic CrizR1 cells upon MYC downregulation using siRNA. Early apoptosis P =0.002, late apoptosis P=0.04, alive P =0.0008.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "F) qPCR of Survivin (P=0.0009), MCL-1 (P=0.04), MYC (P=0.007) and BIM (P=0.03) in Ste-1 AlectR cells xenografts treated with alvocidib (Control n=6; alvocidib n=4).",
    "ncbi_link": "BIM: 10018
Survivin: 332
MCL-1: 4170
MYC: 4609"
  },
  {
    "caption": "(A) Schematic overview of FMR1, FXR1, FXR2, FMR2 and position of the 8 selected single nucleotide polymorphisms (SNPs). Line represents introns, grey box at the beginning and end of each gene stands for UTR region and red boxes represent exons. Gene structure plots generated using FancyGene (Rambaldi & Ciccarelli, 2009)",
    "ncbi_link": "FMR2: 2334
FMR1: 2332
FXR1: 8087
FXR2: 9513"
  },
  {
    "caption": "(B) Distribution of repeat polymorphism lengths in FMR1 of male GRAS schizophrenia patients and healthy controls. (C) Distribution of repeat polymorphism lengths in FMR2 of male GRAS schizophrenia patients and healthy controls.",
    "ncbi_link": "FMR2: 2334
FMR1: 2332"
  },
  {
    "caption": "(A) FXR1 expression in PBMC of individuals carrying the rs2601 GG (low risk; N=16) versus AA genotype (high risk; N=27).",
    "ncbi_link": "rs2601: 
FXR1: 8087"
  },
  {
    "caption": "(B) PBMC microRNA expression was normalized and data is plotted from all 4 miR-181-5p members (miR-181a, b, c, d-5p).",
    "ncbi_link": "miR-181: RF00076"
  },
  {
    "caption": "(C) Sequence homology of all 4 human mature miR-181 species shown together with sequences in the broader fragile X gene family containing binding sites for the miR-181 family (seed matches identified using Target Scan Human and SFOLD). The red letters specify seed sequences and seed matches, respectively. Chromosome positions for each seed sequence and seed match are denoted (human genome assembly GRCh38/hg38).",
    "ncbi_link": "miR-181: RF00076"
  },
  {
    "caption": "(D) Denoted are ΔΔG values for binding of each of the miR-181 family members to different 3'UTR positions. Positions were identified using Target Scan Human and SFOLD and then processed using PITA algorithm to yield the denoted ΔΔG values. ΔΔG is an energetic score, and the more negative its value, the stronger is the expected binding of the microRNA to the given site",
    "ncbi_link": "miR-181: RF00076"
  },
  {
    "caption": "(A) Ventricular weight to tibia length ratio (VW/TL) of littermate control (LC) or cardiomyocyte-specific NCoR1 knockout (CMNKO) mice. n=10:9:12:7.",
    "ncbi_link": "NCoR1: 20185"
  },
  {
    "caption": "(A) Western blotting analysis of NCoR1 in neonatal rat ventricular myocytes (NRVMs) transfected with siControl or siNCoR1 for 3 days. siControl indicates control siRNA; siNCoR1, NCoR1 siRNA.",
    "ncbi_link": "NCoR1: 54299"
  },
  {
    "caption": "(C) Quantification of the surface area of α-Actinin-positive NRVMs with or without NCoR1 knockdown. A total of 40 NRVMs was randomly chosen from 4 replicate coverslips for each group and used for statistical analysis.",
    "ncbi_link": "NCoR1: 54299"
  },
  {
    "caption": "(D) qRT-PCR analysis of Acta1 and Nppa in NRVMs with or without NCoR1 knockdown. n=4:4.",
    "ncbi_link": "Acta1: 29437
NCoR1: 54299
Nppa: 24602"
  },
  {
    "caption": "(E) Western blotting analysis of NCoR1-flag in NRVMs infected by control lentivirus (Control) or NCoR1-flag lentivirus (NCoR1-OV) for 4 days.",
    "ncbi_link": "flag: 
NCoR1: 54299"
  },
  {
    "caption": "(G) Quantification of the surface area of α-Actinin-positive NRVMs with or without NCoR1 overexpression. A total of 30 NRVMs was randomly chosen from 3 replicate coverslips for each group and used for statistical analysis.",
    "ncbi_link": "NCoR1: 54299"
  },
  {
    "caption": "(H) qRT-PCR analysis of Acta1 and Nppa in NRVMs with or without NCoR1 overexpression. n=4:3. Data represent three independent experiments. Two-way ANOVA followed by Bonferoni post-tests was used for statistical analysis.",
    "ncbi_link": "Acta1: 29437
NCoR1: 54299
Nppa: 24602"
  },
  {
    "caption": "(A) Representative immunofluorescence staining of α-Actinin in NRVMs transfected with siRNA for 48h and then treated with vehicle (H2O) or PE for another 48h. Scale bar: 50μm. siMEF2a indicates MEF2a siRNA.",
    "ncbi_link": "MEF2a: 309957"
  },
  {
    "caption": "(B) Quantification of the surface area of α-Actinin-positive NRVMs with or without knockdown of NCoR1 and/or MEF2a. A total of 15-20 NRVMs was randomly chosen from 3 replicate coverslips for each group and used for statistical analysis.",
    "ncbi_link": "MEF2a: 309957
NCoR1: 54299"
  },
  {
    "caption": "(C) Representative immunofluorescence staining of α-Actinin in NRVMs transfected with siRNA for 48h and then treated with vehicle or PE for another 48h. Scale bar: 50μm. siMEF2d indicates MEF2d siRNA.",
    "ncbi_link": "MEF2d: 81518"
  },
  {
    "caption": "(D) Quantification of the surface area of α-Actinin-positive NRVMs with or without knockdown of NCoR1 and/or MEF2d. A total of 15-19 NRVMs was randomly chosen from 3 replicate coverslips for each group and used for statistical analysis.",
    "ncbi_link": "MEF2d: 81518
NCoR1: 54299"
  },
  {
    "caption": "(E) qRT-PCR analysis of Acta1 and Nppa in NRVMs. n=4. Data represent three independent experiments. Student's t test was used for statistical analysis.",
    "ncbi_link": "Acta1: 29437
Nppa: 24602"
  },
  {
    "caption": "(A) Luciferase assays of Acta1 and Nppa promoters in HEK293FT cells transfected with NCoR1-Flag and/or MEF2a-HA or with empty plasmids. Student's t test was used for statistical analysis",
    "ncbi_link": "Flag: 
HA: 
MEF2a: 17258
NCoR1: 20185"
  },
  {
    "caption": "(B) Co-immunoprecipitation (Co-IP) analysis of NCoR1 and MEF2a in HEK293FT cells transfected with full-length NCoR1-Flag and MEF2a-HA.",
    "ncbi_link": "Flag: 
HA: 
MEF2a: 17258
NCoR1: 20185"
  },
  {
    "caption": "(E) Luciferase assays of Acta1 and Nppa promoters in HEK293FT cells transfected with full-length MEF2a and domain-specific NCoR1. Student's t test was used for statistical analysis",
    "ncbi_link": "MEF2a: 17258
NCoR1: 20185"
  },
  {
    "caption": "(F) Western blotting analysis of NCoR1-flag in NRVMs infected by control lentivirus (Control) or NCoR1 (1939-2453)-flag lentivirus [NCoR1(1939-2453)-OV] for 4 days.",
    "ncbi_link": "flag: 
NCoR1: 20185"
  },
  {
    "caption": "(I) qRT-PCR analysis of Acta1 and Nppa in NRVMs. n=4:4. Data represent three independent experiments. Two-way ANOVA followed by Bonferoni post-tests was used for statistical analysis",
    "ncbi_link": "Acta1: 29437
Nppa: 24602"
  },
  {
    "caption": "(A) ChIP analysis showing enrichment of NCoR1 in MEF2 binding regions on the promoters of Acta1 and Nppa in ventricular samples.",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "(B) ChIP analysis of enrichment of MEF2a on promoters of Acta1 and Nppa in ventricular samples. n=3:3.",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "ChIP analysis of enrichment of HDAC4 (C) on promoters of Acta1 and Nppa in ventricular samples. n=4:4 for (C)",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "ChIP analysis of enrichment of HDAC5 (D) on promoters of Acta1 and Nppa in ventricular samples. n=3:3 for (D",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "ChIP analysis of enrichment of , acetylated-Histone 4 (ac-H4) (E) on promoters of Acta1 and Nppa in ventricular samples. , n=3:3",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "ChIP analysis of enrichment of ac-H3 (F) on promoters of Acta1 and Nppa in ventricular samples. n=3:3",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "(G) ChIP analysis of RNA Polymerase II enrichment on the transcriptional regions of Acta1 and Nppa in ventricular samples. n=3:3.",
    "ncbi_link": "Acta1: 11459
Nppa: 230899"
  },
  {
    "caption": "(A) Western blotting analysis of RIDs of NCoR1 in left ventricular samples from mice infected with AAV9 GFP or AAV9 NCoR1-RIDs (1939-2453)-Flag.",
    "ncbi_link": "Flag: 
GFP: 
NCoR1: 20185"
  },
  {
    "caption": "Adult wings from Dl∆β1-2 flies. No defects are detected in wings from Dl∆β1-2/+ (B), Homozygous Dl∆β1-2/ Dl∆β1-2 have extra vein tissue near L5 and uneven L2 veins (arrowheads; C).",
    "ncbi_link": "Dl: 42313"
  },
  {
    "caption": "Microchaetae are arranged in rows on the thorax of control (yw) flies; these become disordered and more dense in Dl∆β1-2/Dl∆β1-2. White rectangle indicates area scored for E Number of microchaetes per central area (white rectangle in D) in the indicated genotypes.",
    "ncbi_link": "Dl: 42313"
  },
  {
    "caption": "Representative images of adult females wings in combinations of Dl∆β1-2 with loss of function Delta alleles. In combinations with Dlrev10 (A), Dl∆Exon2 (B), or Df(3R)DlFx3 (C), vein thickening is strongly enhanced (right panels) compared to heterozygous mutants alone (left panels). Vertical square brackets indicate the regions used for vein thickness quantification. Quantification of wing-vein thickness in females of the indicated genotypes. Representative images of adult female wings demonstrate that Dl∆β1-2 rescues the wing notching phenotype, caused by a Notch loss of function allele (N55e11). Horizontal square bracket indicates the L5 vein "delta" at the intersection with the wing margin analyzed in EV2E. Quantification of wing notching in females of the indicated genotypes, Dl∆β1-2 rescues notching in a similar manner to Dlrev10.",
    "ncbi_link": "Df: 248315
Dl: 42313
Delta: 42313
delta: 42313
Notch: 31293"
  },
  {
    "caption": "Equatorial region of eye imaginal discs where E(spl)mδ0.5 expression (green) becomes restricted to a single photoreceptor in each cluster (magenta), as detected in control and Dl∆β1-2/+ discs (top panels). In Df(3R)DlFx3 /+ and Dl∆β1-2/Df(3R)DlFx3 discs (bottom panels) E(spl)mδ0.5 expression is reduced (Df(3R)DlFx3 /+) or absent from several clusters (Dl∆β1-2/Df(3R)DlFx3) indicative of reduced Notch signalling. Scale bars correspond to 10 μm.",
    "ncbi_link": "Df: 248315
Dl: 42313
Notch: 31293"
  },
  {
    "caption": "Proportion of photoreceptors clusters that fail to express the E(spl)mδ0.5 reporter in the indicated genotypes. ns, no significant difference, *** P<0.0001 (one-way ANOVA). On the violin plot, dashed line represents the median and the dotted lines show the quartiles.",
    "ncbi_link": "E(spl)mδ: 43150"
  },
  {
    "caption": "Schematic diagram of ATXN8OS (top strand) and ATXN8 (bottom strand). RNA-seq read coverage visualized by Integrative Genomic Viewer across the ATXN8/ATXN8OS locus is depicted.",
    "ncbi_link": "ATXN8: 724066
ATXN8OS: 6315"
  },
  {
    "caption": "B Bar graph showing relative mRNA levels of ATXN8 and ATXN8OS. FPKM values for each transcript are normalized to FPKM value for ATXN8OS. (****; p<0.0001; mean ± SEM; unpaired t test) FPKM= fragments per kilo base of transcript per million mapped reads.",
    "ncbi_link": "ATXN8: 724066
ATXN8OS: 6315"
  },
  {
    "caption": "qRT-PCR showing Eif3f expression levels are increased 2-fold in SCA8 cerebellar white matter compared to SCA8 cerebellar grey matter (n=3, **p<0.01; mean ± SEM; unpaired t test).",
    "ncbi_link": "Eif3f: 66085"
  },
  {
    "caption": "C Dot blot detection of polySer expressionin using α-FLAG antibody showing decrease in RAN polySer but not ATG-polySer when HEK293 cells are co-transfected with eIF3F siRNA. D Quantification of polySer detection (n=5, * p<0.01; n.s. no significance; mean ± SEM; unpaired t test). ",
    "ncbi_link": "eIF3F: 8665"
  },
  {
    "caption": "E Detection of polyAla expression using α-HA antibody showing decrease in RAN polyAla but not ATG-polyAla when HEK293 cells are co-transfected with eIF3F siRNA. F Detection of polyGP expression using α-FLAG antibody showing a decrease in RAN polyGP when HEK293 cells are co-transfected with eIF3F siRNA.. G Quantification of polyAla and polyGP detection (n=5, * p<0.01; n.s. no significance; mean ± SEM; unpaired t test). ",
    "ncbi_link": "eIF3F: 8665"
  },
  {
    "caption": "Percentages of SCGB1A1+SFTPC+ (BALO), SCGB1A1+SFTPC- (bronchiolospheres) and SCGB1A1-SFTPC+ (alveolospheres) organoids per well at day 21 of culture derived from EpCAMhighCD24lowSca-1+ cells isolated from Scgb1a1mCherrySftpcYFP reporter mice (n=4 biological replicates).",
    "ncbi_link": "YFP: 
mCherry: 
Scgb1a1: 22287
Sftpc: 20389"
  },
  {
    "caption": "Representative confocal images of days 8 to 21 of culture showing endogenous SCGB1A1 and SFTPC expression during BALO formation derived from EpCAMhighCD24lowSca-1+SCGB1A1+SFTPC+ cells isolated from Scgb1a1mCherrySftpcYFP reporter mice.",
    "ncbi_link": "mCherry: 
YFP: 
Scgb1a1: 22287
Sftpc: 20389"
  },
  {
    "caption": "Violin plots of selected genes representing airway associated-genes (G) (Itgb4, Trp63, Krt7, and Sox2) and alveoli associated‑genes (H) (Cxcl15, Lyz2, Sftpc, and Hopx). Each violin plot shows the frequency distribution of the mean transcript level (log2).",
    "ncbi_link": "Cxcl15: 20309
Hopx: 74318
Itgb4: 192897
Krt7: 110310
Lyz2: 17105
Sftpc: 20389
Sox2: 20674
Trp63: 22061"
  },
  {
    "caption": "mRNA expression analysis of epithelial cell differentiation markers Sftpc (AEC II), Hopx (AEC I), Foxj1 (ciliated cells), Muc5ac (secretory cells) and p63 (basal cells) in BALO at days 0, 10, and 21 of culture (n=3 biological replicates with pooled cells from 4 cultures per replicate)",
    "ncbi_link": "Foxj1: 15223
Hopx: 74318
Muc5ac: 17833
Sftpc: 20389
p63: 22061"
  },
  {
    "caption": "Representative flow cytometric dot plots and histograms of PDGFRα expression in rMC (EpCAM-CD45-CD31-Sca-1+) isolated from the lung homogenate of PdgfraGFP reporter mice.",
    "ncbi_link": "GFP: 
Pdgfra: 18595"
  },
  {
    "caption": "tSNE plots and violin plots depicting selected genes representing MYO (Pdgfrα, Tagln, Acta2, Eln, and Axin2) (top panels) and LIF associated-genes (Fgf10, Apoe, Serpina3n, Gsn, and Gas6) (bottom panels). Each violin plot shows the frequency distribution of the mean transcript level (log2). C3 (MYO, orange) and C4 (LIF, green) refer to the scRNA-Seq experiment in Fig. 1G.",
    "ncbi_link": "Acta2: 11475
Apoe: 11816
Axin2: 12006
Eln: 13717
Fgf10: 14165
Gas6: 14456
Gsn: 227753
Pdgfrα: 18595
Serpina3n: 20716
Tagln: 21345"
  },
  {
    "caption": "Representative images of E11.5 lung explants after treatment for 48 h with 100 μM Scra or mo142-3p reveals reduced size and branching morphogenesis after miR142-3p knockdown.",
    "ncbi_link": "miR142-3p: 387160"
  },
  {
    "caption": "mRNA levels of epithelial and mesenchymal miR142-3p expression in Scra and mo142-3p-treated organoids 5 days after treatment (n=3-4 biological replicates with pooled cells from 4 cultures per replicate).",
    "ncbi_link": "miR142-3p: 387160"
  },
  {
    "caption": " Relative NP expression in PR8 IAV infected (HA+) or non-infected (HA-) epithelial cells isolated from BALO 48 h pi, FACS-sorted according to EpCAM and HA expression (n=3 biological replicates with pooled cells from 4 cultures per replicate) ",
    "ncbi_link": "NP: 956531"
  },
  {
    "caption": " Representative fluorescence images of a day 21 distal region in BALO generated from mTmG reporter mouse and infected by SC35M-Cre IAV after 0, 10, 14 and 25 h. Arrows indicate cell death. Scale bars represent 25 μm and 10 μm in the insert ",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": " mRNA expression of Ifnb in mock and PR8 IAV-infected BALO at 48 h pi (n=3 biological replicates with pooled cells from 4 cultures per replicate) ",
    "ncbi_link": "Ifnb: 15977"
  },
  {
    "caption": "(a) Cell death was analysed after the activation of death pathways in the presence and absence of enforced Atg5 expression (18 h cultures). Values are means ± s.e.m. of three independent experiments.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(b) The cell death regulated by Atg5 is apoptosis. All data presented are from 5 h cultures. Caspase-3-like activity analysed in HeLa cells (graph). Morphology of Jurkat cells is also shown. The numbers in the lower right corner indicate the percentage of cell death, which was determined in parallel experiments using flow cytometry",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "c) Staurosporine induced redistribution of phosphatidylserine was enhanced in Atg5 overexpressing Jurkat cells and blocked by z-VAD-fmk. Numbers indicate the results of the quantitative analysis (percentage) of each dot blot.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "d) Reduction of drug-induced cell death by silencing of Atg5. Values are means ± s.e.m. of three independent experiments (18 h cultures). The effects of the Atg5 siRNA on Atg5 and GAPDH levels were analysed by immunoblotting. The asterisks indicate P 0.05. n.s., no significant difference.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "a) Spontaneous neutrophil apoptosis. Apoptosis was associated with the appearance of a 24K anti-Atg5-reactive protein. 33K Atg5 disappeared during apoptosis in a time-dependent manner. HeLa cells overexpressing Atg5 served as positive control.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(h) Atg5 is not cleaved in apoptotic HeLa cells (5 h staurosporine treatment) lacking the small subunit of calpain, which was silenced by using specific siRNA.",
    "ncbi_link": "calpain: 824///823"
  },
  {
    "caption": "(i) Calpain resistant Atg5Δ191-196 was unable to sensitize HeLa cells lacking endogeneous Atg5 (due to gene silencing, see Fig. 1c) to staurosporine-induced cell death. Values are means ± s.e.m. of three independent experiments (18 h cultures).",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(a) HeLa cells were transiently transfected with 24K and 33K Atg5 for 24 h and subsequently analysed by Hoechst staining. Values are means ± s.e.m. of three independent experiments. Bax transfection was used as a positive control. (b) Representative images after Hoechst staining demonstrating nuclear fragmentation of HeLa cells that were transfected with 24K Atg5 using lentiviral gene transfer for 24 h. Quantitative analysis of these experiments is shown in a. Control and transfected cells were loaded with Mitotracker orange and subsequently processed for cytochrome c immunostaining. Enforced expression of 24K Atg5 resulted in cytochrome c release into the cytosol and apoptosis (nuclear condensation, cell shrinkage; approximately 80% of the cells).",
    "ncbi_link": "Atg5: 9474
Bax: 581"
  },
  {
    "caption": "(c) Jurkat cells were transfected with 24K and 33K Atg5 using lentiviral gene transfer. Cell death was observed as a consequence of enforced expression of truncated Atg5 within two days. Morphological analysis (Diff-Quik) is also shown and revealed that the type of death was apoptosis (nuclear condensation, cell shrinkage).",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(d) CEM cells that either lacked Bcl-2 or expressed high levels of Bcl-2 received truncated Atg5 or GFP by lentiviral gene transfer. In the absence of Bcl-2, induction of apoptosis as assessed by DNA fragmentation was observed due to enforced expression of truncated Atg5 within two days. Apoptosis was largely blocked in cells expressing high levels of Bcl-2. GFP transfection did not affect viability of the cells in this system.",
    "ncbi_link": "Atg5: 9474
Bcl-2: 596"
  },
  {
    "caption": "(e) Staurosporine-induced Atg5 cleavage (5 h treatment) in CEM cells independent of Bcl-2 expression. Blots were stripped and reprobed with anti-GAPDH antibody.",
    "ncbi_link": "Bcl-2: 596"
  },
  {
    "caption": "(f) Detection of autophagic activity by staining of acidic vesicular organelles (VAOs, red) followed by flow cytometry analysis in genetically modified HeLa cells. That 24K Atg5 did not induce autophagy was confirmed by transmission electron microscopy (data not shown).",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(g) Cell death after 24K Atg5 gene transfer in HeLa cells exhibiting different autophagic activities. Values are means ± s.e.m. of three independent experiments (lentiviral gene transfer for 24 h). The asterisks indicate P 0.05. n.s., no significant difference. The scale bars represent 10 μM.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(d) HeLa cells were transfected with 24K and 33K Atg5 using lentiviral gene transfer for 24 h and analysed for caspase-3 cleavage. GAPDH expression demonstrates equal loading.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "C,D Co-expression via the col-19 promoter of UbG76V-GFP (green) and mRFP (red) in C. elegans hypodermis from a single integrated transgene at L4+48 hours. Wild-type animals are shown. Bar, 50 microns. UbG76V-GFP fluorescence is barely detectable.E,F Co-expression via the sur-5 promoter of UbG76V-GFP (green) and mCherry (red) in C. elegans from two separate integrated transgenes (with focus on the intestine) at L4+48 hours. Wild-type animals are shown. Bar, 50 microns. UbG76V-GFP fluorescence is barely detectable.G,H Co-expression of UbG76V-GFP (green) and mRFP (red) in C. elegans hypodermis at L4+48 hours in dop-1(vs100) mutants. Bar, 50 microns. Abundant, stable UbG76V-GFP fluorescence is observed.I,J Co-expression of UbG76V-GFP (green) and mCherry (red) in C. elegans from the sur-5 promoter at L4+48 hours in dop-1(vs100) mutants. Bar, 50 microns. Abundant, stable UbG76V-GFP fluorescence is observed, particularly in the intestine.",
    "ncbi_link": "dop-1: 180714
sur-5: 180992"
  },
  {
    "caption": "M Quantified fluorescence of UbG76V-GFP normalized to mCherry (both expressed by the sur-5 promoter) in the intestine of animals at L4+48 hours and of then indicated genotypes. ***P<0.001, **P<0.01, *P<0.05, ANOVA with Dunnetts posthoc comparison to the wild-type control. N=20 animals per genotype and timepoint. Error bars indicate SEM.",
    "ncbi_link": "sur-5: 180992"
  },
  {
    "caption": "B Western blot of lysed nematodes at the L4+48 hour stage, probed and annotated as in (A). Animals express UbG76V-GFP protein from the sur-5 promoter. Thirty animals were loaded per lane for each indicated genotype (WT indicates wild type).",
    "ncbi_link": "sur-5: 180992"
  },
  {
    "caption": "A Relative abundance of mRNA for the indicated xenobiotic stress response gene (or UbG76V-GFP or mRFP) detected in wild type versus dop-1 mutants. Values are based on RNA-seq/EdgeR analysis, with the relative levels for each gene normalized to the value observed in the wild-type control. ****P<0.0001, **P<0.01, *P<0.05 FDR from EdgeR analysis using a Benjamini and Hochberg correction.",
    "ncbi_link": "dop-1: 180714
Ub: 175840///176718"
  },
  {
    "caption": "C Survival curves (percentage of live animals assayed each hour after PA14 exposure) for the indicated mutants at 20oC. Plog-rank<0.0001. Median survival time was 90 hours for wildtype (N=304), 72 hours for dop-1(vs100) (N=180), 78 hours for elt-3(gk121) (N=120), 78 hours for pqm-1(ok485) (N=116), 78 hours for nhr-28(gk568) (N=123), and 42 hours for skn-1(tm3411) (N=33). Eight wild-type animals and six dop-1 mutants were censored (the animals crawled up the side of the plate and dessicated). The media contained 50 µg/ml of 5-fluoro-2′-deoxyuridine (FUdR to prevent the growth of egg offspring during the experiment.",
    "ncbi_link": "dop-1: 180714
elt-3: 181503
nhr-28: 181705
pqm-1: 174705
skn-1: 177343"
  },
  {
    "caption": "(D and E) BMDMs from WT mice were treated with LPS (100 ng/ml) or rRv2626c for indicated times (D). BMDMs from WT, TLR2-/-, TLR4-/-, MyD88-/-, TRIF-/-, IRAK1-/-, TRAF6-/-, TBK1-/- mice were treated with 2.5 μg/ml rRv2626c or rVector for 18 h (E). Culture supernatants were harvested, and the levels of TNF-α, IL-6, IL-12p40, and IL-10 were measured by ELISA.",
    "ncbi_link": "IRAK1: 16179
MyD88: 17874
TBK1: 56480
TRIF: 225471
TLR2: 24088
TLR4: 21898
TRAF6: 22034"
  },
  {
    "caption": "(B) 293T cells were co-transfected with Flag-TRAF6 and Myc-Rv2626c and IP with αFlag or αMyc. WCLs were used for IB with αFlag, αMyc or αActin.",
    "ncbi_link": "Flag: 
Myc: 
Rv2626c: 
TRAF6: 22034"
  },
  {
    "caption": "(A) Schematic diagram of the structures of Rv2626c (up). 293T cells were co-transfected with Flag-TRAF6 together with GST-vector or GST-Rv2626c and its mutant constructs, subjected to GST pulldown, followed by IB with αFlag. WCLs were used for IB with αGST, αFlag or αActin (down).",
    "ncbi_link": "Flag: 
GST: 
Rv2626c: 
TRAF6: 22034"
  },
  {
    "caption": "(B) At 12 hr post-transfection with mammalian Myc-Rv2626c constructs together with Flag-TRAF6 and 293T cells treated with several Tat-CBS2 peptide for 12 h (10 µM) for 6h, subjected to IP with αMyc, followed by IB with αFlag. WCLs were used for IB with αMyc, αFlag or αActin.",
    "ncbi_link": "Flag: 
Myc: 
Rv2626c: 
TRAF6: 22034"
  },
  {
    "caption": "(C) Schematic diagram of the structures of TRAF6 (up). 293T cells were co-transfected with Myc-Rv2626c together with GST-vector or GST-TRAF6 and its mutant constructs, subjected to GST pulldown, followed by IB with αMyc. WCLs were used for IB with αGST, αMyc or αActin (down).",
    "ncbi_link": "GST: 
Myc: 
Rv2626c: 
TRAF6: 22034"
  },
  {
    "caption": "(D) 293T cells were co-transfected with Flag-TRAF6, Myc-Rv2626c as indicated doses and HA-ubiquitin (left), HA-K48-linked ubiquitin (middle), HA-K63-linked ubiquitin (right) and then IP with αFlag, followed by IB with αHA. WCLs were used for IB with αFlag , αMyc, or αActin.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Rv2626c: 
ubiquitin: 
TRAF6: 22034"
  },
  {
    "caption": "(E) Myc-Rv2626c-expressing Raw264.7 or THP-1 cells were pretreated with rRv2626c-WT (2.5 μg/ml), rRv2626c-CA (10 ng/ml), rRv2626c-DN (2.5 μg/ml), for 1 h, and stimulated with 100 ng/ml LPS for 30 min, followed by IP with αMyc or αTRAF6, IB with αMyc and ubiquitin. WCLs were used for IB with αMyc, αTRAF6, αHis or αActin.",
    "ncbi_link": "Myc: 
Rv2626c: "
  },
  {
    "caption": "(C) CD86, iNOS, CD163 and Arg1 mRNA levels were determined by real-time PCR.",
    "ncbi_link": "Arg1: 11846
CD163: 93671
CD86: 12524
iNOS: 18126"
  },
  {
    "caption": "Targeted gene delivery into LN229, U87 and SNB19 cells by RGD4C/AAVP-Luc carrying the Luc reporter gene. Cells were seeded in 48 well plates before transduction. Non-targeted/AAVP-Luc was used as negative control for targeted transduction. Results represent the average Relative Luminescence Units (RLU)/1μg protein. Data shown are representative of two experiments, n=3.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Induction of Grp78 promoter activity by TMZ in RGD4C/AAVP-Grp78-Luc cells. LN229, U87 and SNB19 cells stably transduced with RGD4C/AAVP-Grp78-Luc or RGD4C/AAVP-CMV-Luc were grown in the presence of TMZ for the indicated times. Results represent the average RLU/1μg protein. Data shown are representative of two experiments, n=3. Two-way ANOVA with Bonferroni correction (GraphPad Prism 6) was used for data analysis.",
    "ncbi_link": "Luc: 
Grp78: 3309"
  },
  {
    "caption": "TMZ induction of phospho-eIF2α and ATF6-p90 expression. Human glioblastoma cells transduced with RGD4C/AAVP-Grp78 were analyzed by Western blot following treatment with TMZ (100 μM for LN229 and SNB19, 60 μM for U87). GAPDH was used as a control.",
    "ncbi_link": "Grp78: 3309"
  },
  {
    "caption": "RT-PCR analysis of constitutive expression and splicing of XBP1 in glioblastoma cells transduced with RGD4C/AAVP-Grp78, in the presence of TMZ. Sizes of the PCR products were 289 bp for unspliced XBP1 and 263 bp for spliced XBP1, the lower size band is not specific. Time points were selected among those tested in the Western blot in (A), subsequently the image containing 0, 1 and 2 hours was juxtaposed to images of 6, 12 and 24 hours. A white line has been added between the gel pieces that have been juxtaposed.",
    "ncbi_link": "Grp78: 3309
XBP1: 7494"
  },
  {
    "caption": "Tumor cell killing in vitro by the HSVtk/GCV approach. Glioblastoma cells stably transduced with RGD4C/AAVP-Grp78-HSVtk or RGD4C/AAVP-CMV-HSVtk were treated with either GCV (10 μM) or TMZ (100 μM for LN229 and SNB19, 60 μM for U87) or combination of both GCV and TMZ. Cells were stained with MitoSOX and analyzed by FACS at day 4 post-treatment. Data shown are representative of three experiments, n=3. Two-way ANOVA with Tukey's multiple comparison test (GraphPad Prism 6) was used for data analysis.",
    "ncbi_link": "HSVtk: 
Grp78: 3309"
  },
  {
    "caption": "Quantification of the relative homing ability of RGD4C/AAVP-Grp78-HSVtk to brain tumors, brain tissue and pancreas after intravenous administration. The data were normalized both to non-targeted vector and to tissue weight then expressed as relative TU. Data shown are representative of two experiments, n=5. One-way ANOVA with Tukey's multiple comparison test (GraphPad Prism 6) was used for data analysis.",
    "ncbi_link": "HSVtk: 
Grp78: 3309"
  },
  {
    "caption": "In vivo BLI of Luc expression for evaluation of tumor viability and tumor size of representative tumor-bearing mice from all experimental groups before initiation of therapy (day 9 post intracranial cell implantation) and at the end of treatments (day 27 post intracranial cell implantation).",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Targeted transduction of HSJD-GBM-001 and G26 cells, over a time course, by RGD4C/AAVP-Luc. Non-targeted/AAVP-Luc was used as negative control. Results represent RLU/1μg protein of triplicate wells. Data shown are representative of two experiments, n=3. Scale bar, 100 μm.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Treatment of chondrocytes, astrocytes, lung and skin fibroblasts with RGD4C/AAVP-Luc vector, alone or in the presence of TMZ. Non-targeted/AAVP-Luc was used as negative control. Results represent RLU/1μg protein. Data shown are representative of two experiments, n=3. Scale bars, 160 μm for chondrocytes and 80 μm for all other cells.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "E. Q97-GFP was expressed in mia40-3 and corresponding wild type cells for the times indicated. Cells were harvested, washed and survivors were counted after plating on glucose plates. Mean values and standard deviations of three replicates are shown.",
    "ncbi_link": "mia40: 853639"
  },
  {
    "caption": "C. Microscopy images of the indicated strains 12 h after shifting them to galactose. Note that in GAL-Mia40 cells the form and number of aggregates is very different to WT cells. Bar, 5 µm.",
    "ncbi_link": "GAL: 852308
Mia40: 853639"
  },
  {
    "caption": "B. Still frames after different times of growth indicate a uniform fluorescence in Q25-GFP-expressing cells. Q97-GFP expression in wild type leads to many small and scattered aggregates per cell. In GAL-Mia40 cells, Q97-GFP accumulates to much larger intensities but then suddenly collapses into one single aggregate per cell. The arrow depicts aggregate formation. Bars, 4 µm. C. Quantified signal intensities in cells of the indicated mutants. In top and middle graphs, each curve corresponds to a single cell. Averaged signals (mean + SEM) in bottom graph (N=20 for WT, N=17 cells for GAL-Mia40).",
    "ncbi_link": "GAL: 852308
Mia40: 853639"
  },
  {
    "caption": "B. Q97-GFP was expressed for 4.5 h in wild type and GAL-Mia40 cells in two biological replicates each. Cells were lysed with NP-40 before soluble proteins were quantified. Mitochondrial proteins (mito.) and members of the mitochondrial carrier family (carrier) are visualized in a volcano plot. P-values were derived from a moderated t-test. Mitochondrial (mito.) and carrier proteins are indicated by yellow and red dots, respectively. Rnq1 is indicated in blue.",
    "ncbi_link": "GAL: 852308
Mia40: 853639"
  },
  {
    "caption": "C. ∆ura3 cells expressing the Oxa1-Ura3 reporter for the cytosolic accumulation of mitochondrial precursor proteins (Hansen et al., 2018) were transformed with plasmids expressing the proteins TDP-43, the TDP-43Q331K mutant, Q25-GFP, Q97-GFP, α-synuclein, FUS or GFP from a constitutive glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter. Note that the expression of all aggregation-prone proteins (indicated by red arrows) allows cells to grow on uracil-deficient plates indicating the cytosolic accumulation of the Oxa1-Ura3 fusion protein.",
    "ncbi_link": "GFP: 
GPD: 
TDP-43: 
FUS: 2521
α-synuclein: 6622
TDP-43: 23435
glyceraldehyde-3-phosphate dehydrogenase: 853106
ura3: 856692"
  },
  {
    "caption": "E. Wild type cells were transformed with plasmids for the expression of the indicated proteins. Q97-GFPnF is a non-fluorescent version of Q97-GFP. Close proximity of the two split GFP parts results in fluorescence which was visualized by microscopy. Shown are mean values and standard deviations of three replicates. Bar, 5 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B. The open reading frames of the indicated proteins were cloned downstream of a GAL promoter in plasmids and transformed into cells harboring the Q97-GFP expression plasmid. Cells harboring an empty vector (ev) were used for control. Cells were shifted to galactose medium overnight before they were dropped onto glucose or galactose plates. If cells are directly dropped from lactate medium onto galactose plates, only individual cells (indicated by red protein names) escaped the polyQ toxicity (see Fig. EV4C).",
    "ncbi_link": "GAL: 852308"
  },
  {
    "caption": "D. Cells expressing the indicated carrier proteins from GAL promoters were dropped onto galactose plates. Cell growth was quantified by densitometry from one representative plate. OM refers to carrier proteins that were expressed as fusions with an N-terminal outer membrane anchor. See Fig. EV4D, E for scans of the respective plates.",
    "ncbi_link": "GAL: 852308"
  },
  {
    "caption": "B. SH-SY5Y cells co-expressing Q97-GFP with MIA40 (middle row), ∆N-MIA40 (lower row) or a mock-transfected control (upper row) were analyzed by immunocytochemistry and super-resolution microscopy. The magnification shows an enlarged section of the TOM20 staining. TOM20 and TRAP1 serve as markers for the mitochondrial outer membrane and the matrix, respectively. Bars, 20 µm. Magnifications: 40fold of a 63x objective field.",
    "ncbi_link": "MIA40: 131474"
  },
  {
    "caption": "D. SH-SY5Y cells co-expressing Q97-GFP with MIA40 (upper row) or ∆N-MIA40 (lower row) were analyzed by immunocytochemistry and super-resolution microscopy. The magnification shows an enlarged section of the TRAP1 staining used as a marker for the mitochondrial matrix, respectively. Bars, 20 µm. Magnifications: 40fold of a 63x objective field.",
    "ncbi_link": "MIA40: 131474"
  },
  {
    "caption": "C Western blots of the lysates of HEK293T cells, resolved on SDS-PAGE and stained with a pan-arrestin antibody. mt = mock transfected. Bpa: Benzoyl-Phenylalanine. Arrestins were equipped with a 3xHA tag at the C-terminus, which increases their size of about 3 kDa compared to the endogenous proteins (βarr1 47 kDa, βarr2 46 kDa). βarr1 and βarr2 were transfected at 1/3 DNA compared to the corresponding TAG-mutants.",
    "ncbi_link": "βarr1: 281637
βarr2: 281638"
  },
  {
    "caption": "(E) Western blot of whole cells lysates stained with an α-HA antibody. Residues exchanged with BrEtY are indicated in the upper row, mutations at PTH1R are indicated on the left side. The red arrows indicate the two most prominent signals. Red squares indicate signals that vanish upon removal of specific Cys residues in PTH1R.",
    "ncbi_link": "PTH1R: "
  },
  {
    "caption": "A Transcriptome re-analysis of ulp2Δ strains compared with WT (MHY1379) from previous RNA-seq experiments Two-dimensional agglomerative hierarchical clustering shows 2,903 significantly up- or down-regulated genes (P < 0.05) in triplicate RNA samples. Red and blue indicate up and down regulation of genes, respectively, and their intensity represents the relative gene expression changes. B Summery of transcriptome data in (A). White and gray colors indicate up- and down-regulated genes, respectively, in ulp2Δ cells. The pie graph shows the percentages of significantly changed genes, except for 130 ribosomal protein genes (RPs), and are classified by FPKM (Fragments Per Kilobase of Million reads mapped) values in the bar graph. ",
    "ncbi_link": "ribosomal protein: 853701///856776///853565///852105///854715///851611
RPs: 853701///856776///853565///852105///854715///851611
ulp2: 854780"
  },
  {
    "caption": "C qRT-PCR analysis of the highly transcribed PMA1, ADH1 and PYK1 genes in ulp2Δ cells. Expression was measured relative to WT cells and data were normalized to SPT15 expression. Error bars indicate the standard deviations (SDs) from three independent RNA preparations. FPKMs of each gene in WT are shown in the bottom graph.",
    "ncbi_link": "ADH1: 854068
PYK1: 851193
PMA1: 852876
SPT15: 856891
ulp2: 854780"
  },
  {
    "caption": "E ChIP analysis using IgG-Sepharose or anti-Flag-agarose beads in strains expressing TAP-tagged Paf1, Ubc9, or Ulp1 or Flag-tagged Ulp2. An untagged strain (MHY500) was used as a negative control for immunoprecipitation of Ulp2-Flag The qPCR signals of the indicated genes were quantitated and normalized to an internal background control and the input DNA. The primer pairs used are indicated in (D). Quantification presented as fold over background; a value of 1 indicates no signal detected above background signal at a nontranscribed locus, as marked with the horizontal line. Error bars indicate SDs calculated from three independent chromatin preparations. Data information: Asterisks indicate statistically significant differences of Paf1-TAP and Ubc9-TAP with Ulp1-TAP and Ulp2-Flag with No tag in (E) using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "Flag: 
TAP: 
Paf1: 852582
Ubc9: 851495
Ulp1: 856087
Ulp2: 854780"
  },
  {
    "caption": "F Occupancy of Rpb3 and Ulp2 at CUP1 gene was determined by ChIP in a strain expressing Flag-tagged Ulp2 using anti-Rpb3 antibody and anti-Flag agarose beads Mock' indicates use of Protein G beads without added antibody. For CUP1 induction, cells were harvested at the indicated time points after adding CuSO4. "Pro" and "ORF" represent the positions of PCR fragments 1 and 2 from the CUP1 gene Black bar indicates a value of 1, the background signal. Error bars, SD from four independent experiments. Data information: Asterisks indicate significant differences between uninduced and induced cells in (F) using a two-tailed Student's t test (*, P <0.05; **, P <0.01)",
    "ncbi_link": "Flag: 
CUP1: 856450
Ulp2: 854780"
  },
  {
    "caption": "G A percentage graph of association of Ulp2-Flag with genes classified by FPKM RPs and ND indicate ribosomal protein genes and genes not detected genes in our earlier RNA-seq experiments, respectively. The numbers above the graph indicate the total number of yeast genes in each expression category.",
    "ncbi_link": "RPs: 853701///856776///852105///853565///854715///851611
ribosomal protein: 853701///852105///851611///853565///856776///854715"
  },
  {
    "caption": "A Sensitivity of the indicated mutants to 6-AU. All strains carried a URA3 plasmid, pRS316, and were spotted on SD-Ura with or without 6-AU (100 μg/ml); plates were incubated for 2-4 days at 30°C. ULP2 and ulp2(C624A) represent ulp2Δ::HIS3 cells containing either pRS314-ULP2-FLAG or pRS314-ulp2(C624A)-FLAG.",
    "ncbi_link": "FLAG: 
HIS3: 854377
ULP2: 854780
ulp2: 854780
URA3: 856692"
  },
  {
    "caption": "ChIP analyses using anti-Rpb3 (B) antibodies in ulp2Δ cells Error bars indicate the SD from three independent experiments. Data information: Asterisks indicate statistically significant differences determined by pairwise comparisons between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ulp2: 854780"
  },
  {
    "caption": "ChIP analyses using anti-SUMO (C) antibodies in ulp2Δ cells Error bars indicate the SD from three independent experiments. Data information: Asterisks indicate statistically significant differences determined by pairwise comparisons between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ulp2: 854780"
  },
  {
    "caption": "D qRT-PCR analysis of CUP1 mRNA levels in ulp2Δ cells. Data were normalized to ACT1 mRNA levels. CUP1 gene induction was performed Error bars represent the SD from three RNA samples. Data information: Asterisks indicate statistically significant differences determined by pairwise comparisons between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ACT1: 850504
CUP1: 856450
ulp2: 854780"
  },
  {
    "caption": "ChIP assays using anti-Rpb3 antibodies in ulp2Δ cells Pro" denotes the #1 PCR product of PMA1, ADH1 and PYK1 genes , while "ORF" indicates the #3 products of PMA1 and #2 of ADH1 and PYK1; these are used in all ensuing figures except where specified. Error bars indicate the SD from four (E) independent assays. Data information: Asterisks indicate statistically significant differences determined by pairwise comparisons between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01",
    "ncbi_link": "ADH1: 854068
PYK1: 851193
PMA1: 852876
ulp2: 854780"
  },
  {
    "caption": "ChIP assays using anti-SUMO (F) antibodies in ulp2Δ cells ;Pro" denotes the #1 PCR product of PMA1, ADH1 and PYK1 genes while "ORF" indicates the #3 products of PMA1 and #2 of ADH1 and PYK1; these are used in all ensuing figures except where specified. Error bars indicate the SD from three (F) independent assays. Data information: Asterisks indicate statistically significant differences determined by pairwise comparisons between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ADH1: 854068
PYK1: 851193
PMA1: 852876
ulp2: 854780"
  },
  {
    "caption": "A Sensitivity to 6-AU of the indicated cells expressing chromosomally integrated ULP2-Myc derivatives. Assays were performed The schematic diagram below shows full-length Ulp2 with a 9Myc epitope tag and the segments defining the N- and C-terminal domains and the catalytic ULP domain (UD).",
    "ncbi_link": "Myc: 
ULP: 854780
ULP2: 854780
Ulp2: 854780"
  },
  {
    "caption": "C ChIP analysis of Flag-Ulp2 derivatives performed with the same PCR probes W303a cells carrying pRS424-GAL1 plasmids that expressed N-terminally Flag-tagged Ulp2 derivatives-specifically, full-length, NTD (1-403) and CTD (667-1034)-were grown to mid-log phase in SD-Trp medium containing 2% galactose. Error bars indicate the SD from three independent experiments. Data information: Asterisks indicate statistically significant differences compared with WT, full length of Ulp2 (*, P <0.05).",
    "ncbi_link": "Flag: 
GAL1: 852308
Ulp2: 854780"
  },
  {
    "caption": "D Co-IP assay for interaction between Ulp2-Myc derivatives and Flag-H2B in strains transformed with a pRS314 plasmid expressing Flag-tagged H2B. Immunoprecipitated (IP) proteins from anti-Myc agarose beads were analyzed by immunoblotting (IB) using anti-Myc or anti-Flag antibodies. The upper and middle panels show anti-Myc blotting and anti-Flag blotting, respectively. The levels of bound H2B proteins were measured relative to INPUT H2B levels shown in the lower panel.",
    "ncbi_link": "Flag: 
H2B: 851810///852284"
  },
  {
    "caption": "F Quantitation of chromatin association of Ulp2-Myc derivatives in (E). The levels of Ulp2 protein in each fraction were measured by ImageJ and then each signal was divided by the total values for each Ulp2 derivative.",
    "ncbi_link": "Myc: 
Ulp2: 854780"
  },
  {
    "caption": "A Immunoblot analysis of immunoprecipitated Flag-tagged histone H2B with anti-Flag (bottom panel) or anti-SUMO (upper panel) antibodies in WT, ulp2Δ, SUMO-all KR or ulp2Δ SUMO-all KR strains carrying empty vector or pRS426-FLAG-HTB1. One, two or three asterisks represent mono, di and polysumoylated histones, respectively. Note that the apparent diSUMO-H2B species (**) in ulp2Δ SUMO-all KR cells migrates more slowly than H2B linked to a SUMO dimer, suggesting that this species likely represents a low level of H2B with SUMO attached to two different histone lysines (lane 8; also see weaker band in lane 6).",
    "ncbi_link": "FLAG: 
HTB1: 851810
SUMO: 852122
ulp2: 854780"
  },
  {
    "caption": "B Yeast strains of the indicated genotypes and carrying a YCplac33-ULP2 cover plasmid were streaked on SD+5-FOA to evict YCplac33-ULP2; cells were grown at 30°C for 3 days.",
    "ncbi_link": "ULP2: 854780"
  },
  {
    "caption": "C Mutant htb1-K123R ulp2Δ and htb1-K123R ULP2 strains with a pRS316-ULP2 cover plasmid were grown on the indicated plates at 30°C for 2-3 days. Three double mutant isolates were tested in parallel.",
    "ncbi_link": "htb1: 851810
ulp2: 854780
ULP2: 854780"
  },
  {
    "caption": "D Mutant ulp2Δ bre1Δ strains carrying a pRS426-ULP2 (URA3) cover plasmid and the indicated plasmids were grown on SD-Ura and SD+5-FOA at 30°C for 2-3 days.",
    "ncbi_link": "bre1: 851485
ulp2: 854780
ULP2: 854780
URA3: 856692"
  },
  {
    "caption": "E Yeast strains of the indicated genotypes and carrying a YCplac33-ULP2 cover plasmid were streaked on SD+5-FOA to evict YCplac33-ULP2; cells were grown at 30°C for 3 days.",
    "ncbi_link": "ULP2: 854780"
  },
  {
    "caption": "C Chromatin double immunoprecipitation (ChDIP) of Flag-H2B-ub in the indicated strains expressing Flag-H2B. The first ChIP was performed with anti-Flag agarose, and the eluted samples were immunoprecipitated with an antibody against ubiquitin. PCR signals from the indicated genes were normalized to an internal control and the input DNA. The error bars indicate the SD from three independent chromatin samples. Data information: Asterisks indicate statistically significant differences compared with WT in *, P <0.05; **, P <0.01",
    "ncbi_link": "Flag: 
H2B: 852284///851810"
  },
  {
    "caption": "D ChDIP of Flag-H2B-SUMO in the indicated strains expressing both Flag-H2B and HA-SUMO. Chromatin samples were sequentially immunoprecipitated with anti-HA agarose followed by anti-Flag agarose. PCR signals were normalized to the input DNA. The error bars indicate the SD from three independent experiments. Data information: Asterisks indicate statistically significant differences compared with WT *, P <0.05; **, P <0.01",
    "ncbi_link": "Flag: 
HA: 
H2B: 852284///851810
SUMO: 852122"
  },
  {
    "caption": "E ChDIP of Flag-H2B-SUMO in the indicated mutant strains during CUP1 gene induction The CUP1 induction was performed CUP1 OFF and ON indicate uninduced and induced (5 min) conditions, respectively. The error bars represent the SD from three independent ChDIP assays. Data information: Asterisks indicate significant differences between uninduced and induced cells in (E) (*, P <0.05; **, P <0.01).",
    "ncbi_link": "CUP1: 856450"
  },
  {
    "caption": "A The ratio of CTD S2-P relative to Rpb3 at 3' ORF regions was analyzed by ChIP using anti-S2-P and anti-Rpb3 antibodies. The error bars represent the SD from triplicate experiments. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ulp2: 854780"
  },
  {
    "caption": "B A ulp2Δ single mutant and three isolates of ulp2Δ ctk1Δ with YCplac33-ULP2 were grown on SD-Ura or SD+5-FOA plates at 30°C for 2-3 days.",
    "ncbi_link": "ctk1: 853718
ulp2: 854780
ULP2: 854780"
  },
  {
    "caption": "E ChIP analyses of Ctk1-TAP in the indicated strains. The ORF of TFIID-dominated genes indicates position 2 of PCR fragments from the UTH1 and ATP2 genes Error bars represent the SD from triplicate experiments. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "TAP: 
ATP2: 853585
ulp2: 854780
UTH1: 853916"
  },
  {
    "caption": "F Co-IP analysis of Ctk1 and histone H2B interaction. WT and ulp2Δ strains expressing the indicated tagged proteins were precipitated with IgG-Sepharose. IP and INPUT proteins were subjected to immunoblotting with PAP (Ctk1-TAP) and anti-Flag (Flag-H2B) antibodies. Protein signals were quantified relative to PGK and then normalized to the WT value.",
    "ncbi_link": "TAP: 
ulp2: 854780"
  },
  {
    "caption": "G ChDIP of Flag-H2B-SUMO in the indicated strains The "Pro" and "ORF" of UTH1 and ATP2 genes indicate positions 1 and 2 of PCR fragments, respectively The error bars indicate the SD from three independent ChDIPs. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ATP2: 853585
ulp2: 854780
UTH1: 853916"
  },
  {
    "caption": "H Sensitivity to 6-AU of indicated htb1-1 htb2-1 (null alleles for both chromosomal H2B genes) strains carrying pRS314 plasmids that express Flag-H2B or 2SUMO-H2B.",
    "ncbi_link": "Flag: 
htb1-1: 851810
H2B: 851810///852284
htb2-1: 852284
SUMO: 852122"
  },
  {
    "caption": "I, J ChIP analyses of the indicated strains Occupancy of Rpb3 (I) and the ratio of CTD S2-P relative to Rpb3 (J) at 3' ORF regions of the indicated genes were individually analyzed by ChIP Error bars show SD from three independent analyses. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ulp2: 854780"
  },
  {
    "caption": "K ChIP analyses of Ctk1-TAP in the indicated strains. The ORF of TFIID-dominated genes indicates position 2 of PCR fragments from the UTH1 and ATP2 genes Error bars represent the SD from triplicate experiments. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "TAP: 
ATP2: 853585
ulp2: 854780
UTH1: 853916"
  },
  {
    "caption": "L Immunoblot analysis of TAP-tagged Ctk1 proteins in extracts prepared from the strains Anti-PGK blotting shows similar loading.",
    "ncbi_link": "TAP: "
  },
  {
    "caption": "M, N ChIP analyses of the indicated strains Occupancy of Rpb3 (M) and the ratio of CTD S2-P relative to Rpb3 (N) at 3' ORF regions of the indicated genes were individually analyzed by ChIP Error bars show SD from three independent analyses. Data information: Asterisks represent statistically significant differences between WT and ulp2Δ using a two-tailed Student's t test (*, P <0.05; **, P <0.01).",
    "ncbi_link": "ulp2: 854780"
  },
  {
    "caption": "(B) Microarray heat map showing the upregulation in expression of the 11 candidate genes in β cell-ablated versus control islets. Igfbp1a and b were the genes whose expression increased the most after β-cell ablation.",
    "ncbi_link": "Igfbp1a: 317638"
  },
  {
    "caption": "(D-E) Representative images at 6 dpf of Tg(ins:kaede);Tg(ins:CFP-NTR) transgenic larvae that had been injected at the 1-2-cell stage with transposase mRNA (control) or transposase mRNA + bactin:igfbp1a (bactin:igfbp1a), subjected to β-cell ablation by metronidazole (MTZ) during 3-4 dpf, and subsequently allowed to regenerate for 2 days. The GFP+ heart (arrowhead) visualizes successful integration of the construct. Islets are indicated by white arrows. Scale bars: 100 μm. (F) Quantification of β-cell regeneration at 6 dpf in control (n=23), bactin:igfbp1a-overexpressing (n=13), and bactin:igfbp1b-overexpressing (n=8) Tg(ins:kaede);Tg(ins:CFP-NTR) larvae; ***P=0.0002, ns= nonsignificant (P=0.3106).",
    "ncbi_link": "bactin: 57934
igfbp1a: 317638
igfbp1b: 793907
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(G) Immunohistochemistry showing Igfbp1 protein expression in 6 dpf Tg(ins:GFP) following β-cell ablation between 3-4 dpf. Scale bar: 50 μm.",
    "ncbi_link": "ins: 30262"
  },
  {
    "caption": "(H) Both liver-specific (lfabp promoter; n=46) and widespread (bactin promoter; n=18) overexpression of igfbp1a increase β-cell regeneration when compared to control (n=77).",
    "ncbi_link": "bactin: 57934
lfabp: 171481
igfbp1a: 317638"
  },
  {
    "caption": "(I-M) Quantification of β cells with or without β-cell ablation and igfbp1a overexpression by confocal microscopy, which detects even weakly insulin-expressing β cells. Scale bars: 15 μm. See also Figure EV1.",
    "ncbi_link": "igfbp1a: 317638"
  },
  {
    "caption": "(A-C) Igfbp1a promotes β cell regeneration, rather than β cell survival. To trace β cells, we exposed Tg(ins:kaede) larvae to UV light (which causes the existing Kaede protein to switch from emitting green fluorescence to emitting red fluorescence) just before ablating the β cells by MTZ treatment from 3-4 dpf. After regeneration, the newly formed β cells are green, whereas the β cells that survived ablation are yellow (overlap of green and red). (A&B) Representative confocal images at 6 dpf of control and bactin:igfbp1a-overexpressing Tg(ins:kaede);Tg(ins:CFP-NTR) transgenic larvae; arrows indicate surviving (yellow) β cells. Scale bars: 10 μm. (C) Quantification of β cell regeneration (green bars) and β cell survival (yellow bars) per larva at 6 dpf. ***P<0.001: n=20 larvae in the control group; n=27 larvae in the bactin:igfbp1a-overexpressing group.",
    "ncbi_link": "bactin: 57934
Igfbp1a: 317638
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(D-F) Igfbp1a does not promote δ-cell regeneration. We treated control and bactin:igfbp1a-overexpressing Tg(sst:flag-NTR);Tg(sst:dsRed) larvae with MTZ from 3-4 dpf to ablate δ cells, and then allowed them to regenerate until 6 dpf. (D&E) Representative confocal images at 6 dpf of control and bactin:igfbp1a-overexpressing larvae showing comparable number of δ cells after 2 days of regeneration. Scale bars: 15 μm. (F) Quantification of the total number of δ cells per δ-cell ablated larva at 6 dpf compared to the baseline number of δ cells in non-ablated control larvae. P=0.2325. n=13 in the control group, n=7 in the bactin:igfbp1a group.",
    "ncbi_link": "bactin: 57934
Igfbp1a: 317638
igfbp1a: 317638
NTR: 945778
sst: 79186"
  },
  {
    "caption": "(G) Other Igfbps do not promote β-cell regeneration. We injected Tg(ins:kaede);Tg(ins:CFP-NTR) transgenics with either transposase mRNA (control; n=31) or transposase mRNA + one of six different igfbps, igfbp2a (n=25), igfbp2b (n=25), igfbp3 (n=26), igfbp5a (n=17), igfbp6b (n=34), and igfbp7 (n=17), treated them with MTZ from 3-4 dpf to ablate their β cells, and then quantified their β cells after 2 days of regeneration, at 6 dpf; ns=nonsignificant; (igfbp2aP=0.986, igfbp2bP=0.037, igfbp3P=0.979, igfbp5aP=0.999, igfbp6bP=0.997, and igfbp7P=0.999).",
    "ncbi_link": "igfbp2a: 794176
igfbp2b: 798920
igfbp3: 403079
igfbp5a: 795084
igfbp6b: 100301946
igfbp7: 405860
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(H) Tg(pcsk1:GFP) is expressed in regenerating β cells within the islet (arrowheads), but not outside the islet (arrow), at 6 dpf in larvae overexpressing igfbp1a. Scale bar: 15 μm.",
    "ncbi_link": "igfbp1a: 317638"
  },
  {
    "caption": "(I&J) Free-glucose levels during β-cell regeneration in control (bactin:mCherry) and bactin:igfbp1a-overexpressing Tg(ins:kaede);Tg(ins:CFP-NTR) larvae (I), as well as in Tg(ins:kaede);Tg(ins:CFP-NTR) larvae injected in the pericardial sac at 4 dpf with 1 ng of recombinant mouse Igfbp1 (J). We treated larvae with MTZ from 3-4 dpf to ablate their β cells, and monitored their free-glucose levels at 3-7 dpf. Free-glucose levels were significantly lower after genetic igfbp1a overexpression or Igfbp1-protein injection (red lines) than in controls (black lines) at 7 and 6 dpf, respectively. Baseline reference levels of free glucose throughout development are shown for a different set of larvae without β-cell ablation. n=24 larvae (four pools of six larvae) per data point.",
    "ncbi_link": "bactin: 57934
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(A-C) Tg(ins:GFP);Tg(tp1:H2B-mCherry);Tg(ins:Flag-NTR) transgenics, with or without Tg(bactin:igfbp1a), were treated with MTZ from 3-4 dpf to ablate the β cells, and were then allowed to regenerate from 4-6 dpf. Representative confocal images at 6 dpf of control (A) and Tg(bactin:igfbp1a) (B) larvae showing a modest number of ins+ tp1+ co-expressing cells, indicated by arrows, after 2 days of regeneration. Scale bars: 15 μm. (C) Quantification of the total number of β cells (green bars) at 6 dpf, and of β cells expressing Tg(tp1:H2B-mCherry), i.e., of ductal origin (yellow bars). ****P<0.0001, ns= nonsignificant. n=23 larvae in the control group, n=17 larvae in the Tg(bactin:igfbp1a) group.",
    "ncbi_link": "H2B: 
bactin: 57934
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(D-F) Tg(ins:Venus-zGeminin) was examined in control and Tg(bactin:igfbp1a) larvae at 6 dpf, after β-cell ablation 3-4 dpf by using Tg(ins:Flag-NTR). (D-E) Representative confocal images at 6 dpf of control and Tg(bactin:igfbp1a) larvae showing cell cycle activation of β cells in green. Scale bars: 15 μm. (F) Quantification of the total number of β cells with activated cell cycle at 6 dpf, ***P<0.001, n=32 larvae in the control group, n=41 larvae in the Tg(bactin:igfbp1a) group. The number of β cells with activated cell cycle are displayed together with the total number of β cells in experiments with the same setup, ****P<0.0001. n=39 larvae in the control group, n=33 larvae in the Tg(bactin:igfbp1a) group.",
    "ncbi_link": "bactin: 57934
Geminin: 368320
igfbp1a: 317638
NTR: 945778"
  },
  {
    "caption": "(G-I) EdU was used as a marker for cell cycle progression. Tg(ins:H2B-GFP);Tg(ins:Flag-NTR) transgenics, with or without Tg(bactin:igfbp1a), were treated with MTZ from 3-4 dpf to ablate their β cells, and subsequently incubated with EdU during regeneration from 4-6 dpf. (G-H) Representative confocal images at 6 dpf of control and Tg(bactin:igfbp1a) larvae showing β cells in green and the β cells that had incorporated EdU in yellow (green and red overlap; arrowheads). Scale bars: 20 μm. (I) Quantification of the total number of β cells (green bars) at 6 dpf, and of β cells that incorporated EdU (yellow bars) during β-cell regeneration from 4-6 dpf. **P<0.01, ns= nonsignificant. n=16 in both the control and the Tg(bactin:igfbp1a) group.",
    "ncbi_link": "H2B: 
bactin: 57934
igfbp1a: 317638
NTR: 945778"
  },
  {
    "caption": "(J-L) Tg(ins:kaede);Tg(ins:CFP-NTR) transgenics, with or without Tg(bactin:igfbp1a), were injected with a control morpholino or a morpholino that knocked down arx, which is necessary for α-cell differentiation and thus glucagon expression (J-K). Scale bars: 20 μm. (L) Quantification of the total number of regenerating β cells at 4 dpf (after β-cell ablation at 2-3 dpf). ****P<0.0001, *P<0.05, ns=nonsignificant. n=42, 20, 48 and 20, respectively.",
    "ncbi_link": "bactin: 57934
arx: 30657
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(A-E) Control and Tg(bactin:igfbp1a)-overexpressing larvae were treated with MTZ from 3-4 dpf to ablate β cells, and analyzed at 6 dpf, after 2 days of regeneration. (A-B) Representative confocal images of control and Tg(bactin:igfbp1a)-overexpressing Tg(ins:dsRed);Tg(gcg:GFP);Tg(ins:Flag-NTR) larvae. A bihormonal glucagon- and insulin-expressing cell (gcg+;ins+) is indicated by an arrow. Scale bars: 20 μm. (C-D) Representative confocal images of control and Tg(bactin:igfbp1a)-overexpressing Tg(gcg:GFP);Tg(ins:Flag-NTR) larvae stained for Pdx1. Pdx1- and glucagon-expressing cells (pdx1+;gcg+) are indicated by arrows. Scale bars: 20 μm. (E) Quantification of gcg+;ins+ and pdx1+;gcg+ cells in the control and Tg(bactin:igfbp1a) group; P<0.001, P=0.0012; n=18 and 18 in the control groups, n=15 and 10 in the Tg(bactin:igfbp1a) groups, for the gcg+;ins+ and pdx1+;gcg+ quantification, respectively.",
    "ncbi_link": "bactin: 57934
igfbp1a: 317638
NTR: 945778"
  },
  {
    "caption": "(F-I) Lineage-tracing evidence supports α- to β-cell transdifferentiation. (G) Quantification of insulin-expressing cells that originate from α-cells. Control larvae, n=13; bactin:igfbp1a larvae, n=16. P=0.0051.",
    "ncbi_link": "bactin: 57934
igfbp1a: 317638"
  },
  {
    "caption": "(F-I) Lineage-tracing evidence supports α- to β-cell transdifferentiation. (H-I) Representative confocal images at 6 dpf (after 2 days of regeneration) of control and bactin:igfbp1a-overexpressing larvae stained for insulin, glucagon, to-pro, and H2B-GFP. ins+;H2B-GFP+ cells are indicated by the arrowheads, and H' and I' show staining against only insulin and H2B-GFP. Moreover, most insulin+;H2B-GFP+ cells no longer express glucagon. Scale bars: 15 μm.",
    "ncbi_link": "H2B: 
bactin: 57934
igfbp1a: 317638"
  },
  {
    "caption": "(A-H) PPP, an IGF1R inhibitor, promotes β-cell regeneration. Tg(ins:H2B-GFP);Tg(ins:Flag-NTR) larvae were treated with MTZ from 3-4 dpf to ablate the β cells and then treated with EdU and DMSO or with EdU and PPP during regeneration from 4-6 dpf. (A-B) Representative confocal images at 6 dpf of DMSO- and PPP-treated larvae displaying β cells in green and the β cells that had incorporated EdU as yellow overlap (arrowheads). Scale bars: 20 μm. (C) Quantification of the total number of β cells (green bars) at 6 dpf, and β cells that had incorporated EdU (white bars) from 4-6 dpf during β-cell regeneration. P=0.0003, P=0.8607 respectively. (D) Rate of β-cell proliferation, displayed as the percentage of β cells that incorporated EdU. P=0.1194. n=18 larvae for the DMSO-treated group, n=17 larvae for the PPP-treated group. (E-H) To examine whether PPP affected β-cell proliferation during regular development, Tg(ins:H2B-GFP) larvae were treated with EdU and DMSO or PPP from 4-6 dpf. (E-F) Representative confocal images of 6 dpf DMSO- and PPP-treated larvae displaying β cells in green and the β cells that had incorporated EdU as yellow overlap. Scale bars: 20 μm. (G) Quantification of the total number of β cells (green bars) and β cells that had incorporated EdU (white bars) per larva from 4-6 dpf. P=0.9098 and 0.9976, respectively. (H) Rate of β cell proliferation, displayed as the percentage of β cells that incorporated EdU. P=0.7822. n=16 larvae for DMSO-treated group, 18 larvae for PPP-treated group.",
    "ncbi_link": "H2B: 
NTR: 945778"
  },
  {
    "caption": "(I-K) Activation of the Igf pathway reduces β-cell regeneration. Control and bactin:igf2a-overexpressing Tg(ins:H2B-GFP);Tg(ins:Flag-NTR) larvae were treated with MTZ from 3-4 dpf to ablate β cells and subsequently let to regenerate from 4-6 dpf. (I-J) Representative confocal images of 6 dpf control and bactin:igf2a-overexpressing larva displaying β cells in green. Scale bars: 15 μm. (K) Quantification of the total number of β cells per larva at 6 dpf following β cell regeneration from 4-6 dpf. P<0.0001. n=28 larvae for control, n=15 larvae for bactin:igf2a.",
    "ncbi_link": "H2B: 
bactin: 57934
igf2a: 30710
NTR: 945778"
  },
  {
    "caption": "(L-P) No synergistic effect was observed for igfbp1a and PPP. Control and bactin:igfbp1a-overexpressing Tg(ins:H2B-GFP);Tg(ins:Flag-NTR) larvae were treated with MTZ from 3-4 dpf to ablate β cells and subsequently treated with DMSO or PPP during regeneration from 4-6 dpf. (L) Quantification of the total number of β cells per larva. n>10 (n=23, 20, 14, 13). P=0.9546. (M-P) Representative confocal images of 6 dpf control or bactin:igfbp1a overexpressing larvae treated with either DMSO or PPP, displaying β cells after 2 days regeneration. Scale bars: 10 μm. See also Figure EV2 & EV3.",
    "ncbi_link": "H2B: 
bactin: 57934
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(A-B) Representative confocal projections of the whole pancreas (dashed lines) of 35-day-old Tg(ins:H2B-GFP);Tg(ins:Flag-NTR) transgenics, with or without Tg(bactin:igfbp1a), that were subjected to β-cell ablation between day 30-31 and then allowed to regenerate for 4 days. Scale bars represent 100 μm. (C) Body length of control and Tg(bactin:igfbp1a) zebrafish; P<0.0001. (D-H) Quantification of β-cell regeneration was automated with an ImageJ script. (D) Insulin-positive area per zebrafish. (E) Relative insulin-positive area per body length; P<0.01. (F) The percentage of the pancreas area that was insulin-positive was significantly larger in Tg(bactin:igfbp1a) than in controls; P<0.0001. (G) The total number of recorded units of adjacent ins:H2B-GFP+ pixels (units ranging from single β cells to β-cell clusters) did not differ between control and Tg(bactin:igfbp1a) zebrafish. (H) The size of recorded ins:H2B-GFP+ units was on average larger in Tg(bactin:igfbp1a) than in controls; P=0.039. n=26 in the control group, n=27 in the Tg(bactin:igfbp1a) group.",
    "ncbi_link": "H2B: 
bactin: 57934
igfbp1a: 317638
ins: 30262
NTR: 945778"
  },
  {
    "caption": "(A, B) Immunoblot analysis of AGIA-MmPLZF (A) or -MmSALL4 (B) in FLAG-MmCRBN-WT, -MmCRBN-I391V or -MmCRBN-V380E/I391V expressing CRBN-/- HEK293T cells treated with DMSO or thalidomide (Tha) for 16 h. Data information: Data in bar graphs were calculated as relative Mm) PLZF or SALL4 band intensity with Mm) PLZF or SALL4, respectively. The band intensity of DMSO was 100. Error bars denote ± standard deviation (n = 3). P-values were calculated by one-way ANOVA with Tukey's post-hoc test (NS = Not Significant, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001).",
    "ncbi_link": "CRBN: 58799"
  },
  {
    "caption": "(C, D) Immunoblot analysis of AGIA-GgPLZF (C) or -GgSALL4 (D) in FLAG-GgCRBN-WT or -GgCRBN-I390V expressing CRBN-/- HEK293T cells treated with DMSO or thalidomide (Tha) for 16 h. (E, F) Immunoblot analysis of AGIA-Mm PLZF (E) or -MmSALL4 (F) in FLAG-MmCRBN-WT expressing CRBN-/- HEK293T cells treated with indicated concentration of DMSO, thalidomide (Tha) or 5-hydroxythalidomide (5-HT) for 16 h. (G, H) Immunoblot analysis of AGIA-GgPLZF (G) or -GgSALL4 (H) in FLAG-GgCRBN-WT expressing CRBN-/- HEK293T cells treated with indicated concentration of DMSO, thalidomide (Tha) or 5-hydroxythalidomide (5-HT) for 16 h. Data information: Data in bar graphs were calculated as relative (Gg or Mm) PLZF or SALL4 band intensity with (Gg or Mm) PLZF or SALL4, respectively. The band intensity of DMSO was 100. Error bars denote ± standard deviation (n = 3). P-values were calculated by one-way ANOVA with Tukey's post-hoc test (NS = Not Significant, *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001).",
    "ncbi_link": "FLAG: 
CRBN: 416106
CRBN: 58799"
  },
  {
    "caption": "(E) Skeletal patterning of forelimb and hindlimb in E6 chicken embryos infected RCAN virus packaging shControl (n = 10) or shPLZF (n = 9) were analysed by Victoria blue staining. h; humerus, r; radius, u; ulna, fe; femur, fi; fibula, t; tibia. Data in bar graphs were calculated as relative bone length with bone length of shControl as 100. Error bars denote ± standard deviation (forelimb and hindlimb shControl (n = 3), forelimb shPLZF (n = 5) or hindlimb shPLZF (n = 6)). P-values were calculated by one-way ANOVA with Tukey's post-hoc test (**P < 0.01 and ****P < 0.0001).",
    "ncbi_link": "PLZF: 419759"
  },
  {
    "caption": "E3 chicken forelimb bud electroporated with empty pCAGGS or pCAGGS-GgPLZF was treated with HBC or 1 µg/µl (3.9 mM) thalidomide, and the chicken forelimb bud phenotypes were observed in bright field (BF) or fluorescence of enhanced GFP (EGFP). Fgf10/Fgf8 expression was analysed by section by in situ hybridisation. (Q) Quantitative analysis of phenotypes of chicken limb bud Data in bar graphs in (Q) were calculated as relative limb bud length with limb bud length of control embryo as 100. Error bars denote ± standard deviation (n = 3). P-values were calculated by one-way ANOVA with Tukey's post-hoc test (**P < 0.01).",
    "ncbi_link": "PLZF: 419759"
  },
  {
    "caption": "(R) Quantitative analysis of Fgf10/Fgf8 expression Data in bar graphs in (R) were calculated as relative Fgf10/Fgf8 mRNA expressions with Fgf10/Fgf8 mRNA expressions of control embryo as 100. Error bars denote ± standard deviation (n = 3). P-values were calculated by one-way ANOVA with Tukey's post-hoc test (*P < 0.05 and **P < 0.01).",
    "ncbi_link": "Fgf10: 395432
Fgf8: 396313"
  },
  {
    "caption": "(C) PI4KB phosphorylation by PKA alters the affinity for c10orf76. The kinase activity of different variants of PI4KB (15 nM) was measured in the presence of varying amounts of c10orf76 (23 nM-1.5μM) with 100% PI lipid substrate (0.5 mg/L) and 100 μM ATP. The data was normalized to the kinase activity of PI4KB alone Error bars represent standard deviation of independent technical replicates (n=3).",
    "ncbi_link": "PI4KB: 5298"
  },
  {
    "caption": "(D) PI4KB has the same kinase activity when Ser496 is phosphorylated or mutated to alanine. Kinase assay of PI4KB non-phosphorylated, phos-Ser496 or S496A (15 nM) on pure PI lipid vesicles (0.5 mg/L) with 100 μM ATP. The data was normalized to the kinase activity of WT PI4KB. Error bars represent standard deviation of independent technical replicates (n=3).",
    "ncbi_link": "PI4KB: 5298"
  },
  {
    "caption": "(E) Engineered RL494EA PI4KB mutant shows decreased binding to c10orf76. His-pulldown assays of 6xHis-c10orf76 (3 μM) with wild-type or RL494EA PI4KB (1-2 μM).",
    "ncbi_link": "PI4KB: 5298"
  },
  {
    "caption": "(F) RL494EA PI4KB activity is not inhibited by c10orf76. Kinase assays of either wild type or mutant RL494EA PI4KB (40 nM) were carried out with varying concentrations of c10orf76 (3.9 nM-2μM) with 100% PI lipid vesicles (0.5 mg/L) and 100 μM ATP. The data was normalized to the kinase activity of PI4KB alone. Error bars represent standard deviation of independent technical replicates (n=3).",
    "ncbi_link": "PI4KB: 5298"
  },
  {
    "caption": "(G) Wild-type PI4KB and RL494EA PI4KB mutant have the same lipid kinase activity. Kinase assays of either wild-type and mutant PI4KB (10 nM) were carried out with 100% PI lipid vesicles (0.5 mg/L), 100 μM ATP, and PI4KB (300 nM) on Golgi-mimic vesicles (0.5 mg/mL) with 10 μM ATP. The data was normalized to the kinase activity of WT PI4KB. Error bars represent standard deviation of independent technical replicates (n=3).",
    "ncbi_link": "PI4KB: 5298"
  },
  {
    "caption": "(H) FLH409AAA-c10orf76 mutant shows decreased affinity for PI4KB. His-pulldown assays of 6xHis-c10orf76 (1 μM) with wild-type PI4KB (1 μM). Samples washed a total of 4 times.",
    "ncbi_link": "c10orf76: 79591"
  },
  {
    "caption": "(I) Kinase assay shows FLH409AAA c10orf76 inhibition of PI4KB is greatly reduced. Kinase assay of PI4KB (40 nM) and a concentration curve of c10orf76 (3.9 nM-2μM) on pure PI lipid vesicles (0.5 mg/L) with 100 μM ATP. The data was normalized to the kinase activity of PI4KB alone. Error bars represent standard deviation of independent technical replicates (n=3).",
    "ncbi_link": "c10orf76: 79591"
  },
  {
    "caption": "(A) Transfections of HEK293 cells revealed that both wild-type GFP-PI4KB and RL494EA GFP-PI4KB localize to the Golgi.",
    "ncbi_link": "GFP: 
PI4KB: 5298"
  },
  {
    "caption": "(B) WT c10orf76 also localized to the Golgi, however, the PI4KB binding deficient mutant of c10orf76 (FLH409AAA) predominantly localized to the cytosol.",
    "ncbi_link": "c10orf76: 79591"
  },
  {
    "caption": "B) HAP1 cells were fixed and stained with antibodies examining Golgi morphology markers (B). (C) Western blot of GBF1, PI4KB and B-Actin levels in both wild-type and c10orf76 KO HAP1 cells. Data information: Nuclei were stained with DAPI (blue). Scale bars represent 10 μm.",
    "ncbi_link": "c10orf76: 79591"
  },
  {
    "caption": "(A) Viral infection assays determining viral titers by end-point titration at 0 hours and 8 hours in HAP1 wild-type or c10orf76 knockout cells. Left: Coxsackievirus A10 infection. Middle: Poliovirus-1 infection. Right: Coxsackievirus B3 infection. Titre values for c10orf76 knockout cells at 8 hours were statistically evaluated compared to c10orf76 knockout titres at 0 hours and wild-type titres at 8 hours using a one-way ANOVA. **, P<0.01; N.S., P>0.05.",
    "ncbi_link": "c10orf76: 79591"
  },
  {
    "caption": "(B) Viral infection assays determining virus titers by end point titration at 8 hours in HeLa wild-type and PI4KB knockout cells upon transfection of wild-type PI4KB, the complex-disrupting RL494EA PI4KB mutant or the kinase dead D674A PI4KB mutant. Left: Coxsackievirus A10 infection. Middle: Poliovirus-1 infection. Right: Coxsackievirus B3 infection. Values were statistically evaluated compared to the GalT control using a one-way ANOVA. **, P<0.01; *, P<0.05; N.S., P>0.05.",
    "ncbi_link": "GalT: 
PI4KB: 5298"
  },
  {
    "caption": " B) Circulating and resident hemocytes (top and bottom panels, respectively) from Mimic-Lsp1beta-MI05460 WL, which express Lsp1beta tagged with GFP. The immunolabelling was done with anti-GFP (in gray) and the nuclei were marked with DAPI (blue). Full stacks are displayed, the left panels show the overlay of DAPI and GFP, the right panels show the GFP alone. The scale bars represent 10 µm. C) Quantification of the GFP intensity in circulating and resident hemocytes from MiMIC-Lsp1beta-MI05460 larvae. The OregonR value indicates the background level. The number of cells included in the analysis is displayed on the x-axis label and were quantified from two independent preparation, p-values were estimated after variance analysis with bilateral student test for equal variance.",
    "ncbi_link": "GFP.: 
Lsp1beta: 33274"
  },
  {
    "caption": " D) Resident hemocytes located around the oenocytes or along the muscles (top and bottom panels, respectively) from WL srp(hemo)-moesin-RFP, that express moesin tagged with RFP in hemocytes. The immunolabelling was done with anti-RFP (in red), anti-Pendulin (Pen, in gray) and the nuclei were marked with DAPI (blue). Full stacks are displayed, the left panels show the overlay of DAPI, Pen and RFP, the middle panels RFP alone and the right panels Pen alone. Arrow heads in the top panels indicate cells co-expressing RFP and Pen. The scale bars represent 50 µm. ",
    "ncbi_link": "moesin: 
hemo: 12798465
srp: 41944"
  },
  {
    "caption": " E) Weighted dot plot representing the enrichment (Log2 fold change) of the markers in hemocytes originating from the lymph gland (DotGFP-WI) compared to embryonic hemocytes (srpGFP-WI) from WI larva. The lymph gland hemocytes and embryonic hemocytes were traced using the lymph gland driver DotGal4 and the embryonic driver Srp(hemo)Gal4 respectively combined with a lineage tracing construct. The relative expression levels are indicated by the size of the dots and the pvalue of the log2 fold change with the gradient dark blue (not significant) to light blue (p<10-3). The p-value are estimated by bilateral student test and indicated as follow: ns = not-significant (>0.05), \"*\" = p[0.05 - 0.01[, \"**\" = p[0.01-0.001[, \"***\" = p <0.001]. ",
    "ncbi_link": "Dot: 
Gal4: 
GFP: 
hemo: 12798465
srp: 41944
Srp: 41944"
  },
  {
    "caption": "(C) Average delta-F/F signal trace from SON oxytocin neurons with 10 seconds of dim light (5 lux) followed by 30 seconds of bright light (800 lux) in OPN4DTA/DTA; OxtCre/+ mice (red line, n = 4 animals) and OPN4+/+; OxtCre/+ mice (black line, n = 5 animals). The color shade indicates standard deviation.",
    "ncbi_link": "Cre: 2777477
OPN4: 30044
Oxt: 18429"
  },
  {
    "caption": "(B) Light exposure significantly reduces the recognition index in control Opn4Cre/+ mice (n = 8 animals in both the L and D group), similar to WT mice (*p = 0.0499, Mann-Whitney test). Data shown as mean ± SEM. (C-E) There is no significant difference in recognition index between light exposure and dark control groups in OPN4DTA/DTA (C, n = 11 animals in both the L and D group, p = 0.7969), OPN4Cre/+; Brn3bz-DTA/+ (D, n = 9 animals in both the L and D group, p > 0.9999), and OPN4Cre/Cre mice (E, L group n = 9 animals, D group n = 8 animals, p = 0.9551) using the Mann-Whitney test. Data shown as mean ± SEM.",
    "ncbi_link": "Cre: 2777477
Opn4: 30044
OPN4: 30044
Brn3b: 18997"
  },
  {
    "caption": "(I) Average delta-F/F signal trace from pSON GABAergic neurons during the transition from baseline to dim light (5 lux, black line, n = 7 trials) and from baseline to bright light (800 lux, red line, n = 12 trials) in vGATCre/+ mice (n = 5 animals). The color shade indicates standard deviation.",
    "ncbi_link": "Cre: 2777477
vGAT: 22348"
  },
  {
    "caption": "(G) The investigation duration and recognition index of the GFP-control (n = 4 animals) and the TeLC-silencing (n = 6 animals) group. During the second trial, the investigation duration of the TeLC-silencing group was lower than the GFP-control group (* p = 0.0280, Sidak's multiple comparison test). The TeLC-silencing group had a higher recognition index than GFP-control group (* p = 0.0317, Mann-Whitney test). Data shown as mean ± SEM.",
    "ncbi_link": "TeLC: 24255210"
  },
  {
    "caption": "(a) Primary siRNA screening analysis. MDA-MB-231 cells reverse transfected with siRNA pools against MT1-MMP, TKS5, or each human RAB GTPase were plated on fluorescein-labeled-gelatin coated optical microplates. Degradation activity was measured by counting the number of cells degrading gelatin identified as dark black foci (similar results were obtained by measuring the area of degradation/number of cells). The inset shows representative images of degraded Oregon green gelatin (upper panels) and merged images with TRITC-phalloidin (red) and DAPI (blue) in scrambled siRNA (NC), or siRNA against RAB28 or RAB42 transfected cells (lower panel). Data are means ± SEM of 3 independent experiments. Bar, 50 µm.",
    "ncbi_link": "MT1-MMP: 4323
RAB28: 9364
RAB42: 115273
TKS5: 9644"
  },
  {
    "caption": "(c-e) Tertiary siRNA screening. Pooled siRNAs against candidate RAB GTPases identified from the secondary screen or TKS5, used as control, were transfected into MCF10.DCIS.com cells. Cells plated onto fluorescently conjugated gelatin (red) were stimulated with 100 ng/ml HGF overnight in the presence or absence of GM6001, followed by staining with FITC-phalloidin (green) and DAPI (blue) (c). Data are the mean ± SEM (d, error bars; n > 100 cells/experiment in at least 4 independent ones).",
    "ncbi_link": "TKS5: 9644"
  },
  {
    "caption": "(c-e) Tertiary siRNA screening. Pooled siRNAs against candidate RAB GTPases identified from the secondary screen or TKS5, used as control, were transfected into MCF10.DCIS.com cells. Efficacy of targeted gene silencing was verified by qPCR (e). Bar, 50 µm.",
    "ncbi_link": "TKS5: 9644"
  },
  {
    "caption": "(a) Doxycycline-inducible empty vector (EV) or RAB2A-shRNA MDA-MB-231 cells were cultured in the absence (-) or presence (+) of doxycycline for three days, and immunoblotted with anti-RAB2A and anti-actin antibodies. The intensity of RAB2A relative to actin is shown on the bottom. Relative density in uninduced EV cells was set to 1.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(b) Doxycycline-inducible RAB2A-shRNA MDA-MB-231 cells were cultured in the absence (CTR) or presence (shRAB2A) of doxycycline for three days. Invasion of MDA-MB-231 cells through Matrigel-coated transwells toward HGF was assessed after 24 hours. Representative images are shown. Data are the mean ± SD (n=10 field/condition in at least 3 experiments). Bar, 200 µm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(c-e) EV and shRAB2AMDA-MB-231 cells were embedded in Spheroid Formation ECMR in the absence (-) or presence (+) of doxycycline and/or GM6001. After 3 days, the cells were transferred into Invasive MatrixR. Phase contrast light microscopy images of representative spheroids are shown after 9 days (c). Dashed circle indicates the size of spheroids at day 0. Bars, 500 µm. Invasive activity into ECM was expressed as total spheroid area (relative to control cells at day 0) quantified by ImageJ (d). The number of cells at the indicated days was quantified by CyQUANTR Cell Proliferation Assay Kit (e). Data are the mean ± SD (n=3 independent experiments).",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(f-h) Doxycycline-inducible murine RAB2A (mRAB2A)-expression MCF10.DCIS.com cells were transfected with scrambled siRNA or siRNA against human RAB2A (siRAB2A) in the absence (-) or presence (+) of doxycycline. Serum-starved cells were plated onto fluorescently conjugated gelatin (red), stimulated with HGF (100 ng/ml) overnight, and stained with phalloidin (green) and DAPI (blue) (f). Bar, 50 μm. Data are the mean ± SEM (error bars; n > 100 cells/experiment in 4 independent ones) (g). Silencing of endogenous RAB2A protein (lower band) and ectopic RAB2A expression (upper band) was verified by immunoblotting (h). * P < 0.05, **, P < 0.01, ***, P < 0.001, NS, not significant.",
    "ncbi_link": "RAB2A: 5862
RAB2A: 59021"
  },
  {
    "caption": "(a, b) MCF10.DCIS.com cells were transfected with FLAG-empty vector (EV), constitutively active RAB2A-Q65L, or dominant negative RAB2A-S20N mutant. Cells were immunostained with anti-FLAG (red) and RAB7 (a, green) or anti-EEA1 (b) antibodies. Merged images with DAPI (blue) are shown on the right. Enlarged endosomes in the boxed region are highly magnified in the insets. Diameters of RAB7 positive vesicles are also shown. n, number of cells scored for each cell population. The RGB profiler plugin from ImageJ was used to plot colocalization in the lines drawn in the inset images. Bars, 10 μm, (inset 2 μm).",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(c) MDA-MB-231 cells were transfected with EGFP-fused EV, RAB2A-Q65L, or RAB2A-S20N. Cells are immunostained with anti-RAB7 (blue) and anti-MT1-MMP (red) antibodies, and their merged images are shown. Merged images are shown on the right. Enlarged endosomes containing MT1-MMP in the boxed region are highly magnified in the insets. Note that RAB2A-Q65L and RAB7-positive vesicles contain MT1-MMP (arrows). Bars, 10 μm, (inset 2 μm).",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(d-f) MDA-MB-231 cells expressing MT1-MMP-pHluorin transfected with scrambled siRNA (siNC) or siRNA against RAB2A were seeded on type I collagen, and images were acquired for 20 min period by TIRF microscopy. Frequency of MT1-MMP-pHluorin exocytic events was quantified (e). The corresponding time-lapse series are shown in Movie 1, while an entire cell shown in Movie 2. Efficacy of RAB2A gene silencing was verified by qPCR (f). Bars, 2 μm. **, P < 0.01.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(a) Total cellular lysates from HEK293T cells transfected with myc-VPS39 or VPS41 were incubated with GST-empty vector (EV), RAB2A-S20N (SN), or RAB2A-Q65L (QL) proteins bound to glutathione sepharose beads. Immunoblotting was performed with anti-myc antibody. Input lysates are also shown. GST proteins loaded in gels were stained with CBB.",
    "ncbi_link": "RAB2A: 5862
VPS39: 23339
VPS41: 27072"
  },
  {
    "caption": "(b) FLAG-EV or RAB2A were transiently co-transfected with EGFP-VPS39 or VPS41 into HEK293T cells. Immunoprecipitated (IP) fraction from cell lysates with anti-FLAG antibody and total lysates were immunoblotted with the antibodies indicated on the right.",
    "ncbi_link": "RAB2A: 5862
VPS39: 23339
VPS41: 27072"
  },
  {
    "caption": "(c, d) MDA-MB-231 cells were transfected with EGFP-fused empty EV, VPS39, or VPS41. Cells were immunostained with RAB7 (c, red) or anti-MT1-MMP (d) antibodies. Merged images with DAPI (blue) are shown on the right. Enlarged endosomes in the boxed region are highly magnified in the insets. Diameters of RAB7 positive vesicles are also shown. n, number of cells scored for each cell population. Bars, 10 μm, (inset 5 μm).",
    "ncbi_link": "VPS39: 23339
VPS41: 27072"
  },
  {
    "caption": "(e-i) Scrambled siRNA (siNC) or siRNA against RAB2A (siRAB2A), VPS39 (siVPS39), or VPS41 (siVPS41) were transfected into MCF10.DCIS.com cells. Serum-starved cells were then plated onto fluorescent-conjugated gelatin (red), stimulated with HGF (100 ng/ml) overnight, and stained with phalloidin (green) and DAPI (blue). Quantification of gelatin degradation (f) and efficacy of targeted gene silencing verified by qPCR (g-i). Data are the mean ± SEM (error bars; n > 100 cells/experiment in at least 4 independent ones). Bars, 50 µm.",
    "ncbi_link": "RAB2A: 5862
VPS39: 23339
VPS41: 27072"
  },
  {
    "caption": "(m-q) Doxycycline-inducible murine RAB2A-expression MCF10.DCIS.com cells were transfected with siNC, siRAB2A, or siVPS39 in the absence (CTR) or presence (RAB2A) of doxycycline. Their ECM degradation activities were quantified (n). Data are the mean ± SEM (error bars; n > 100 cells/experiment in 3 independent ones). Total cell lysates were immunoblotted by anti-RAB2A and anti-tubulin antibodies (o). Efficacy of targeted gene silencing was verified by qPCR (p-q). Bar, 50 μm. **, P < 0.01, ***, P < 0.001.",
    "ncbi_link": "RAB2A: 59021
RAB2A: 5862
VPS39: 23339"
  },
  {
    "caption": "(a) Doxycycline-inducible RAB2A-shRNA MCF10.DCIS.com cells were incubated on a thick layer of Matrigel for 4 days to allow spheroid formation in the absence (CTR) or presence (shRAB2A) of doxycycline. Cells were stimulated with 5 ng/ml EGF and 20 ng/ml HGF (EGF+HGF) or left starved (STV) for 9 days. Representative phase contrast light microscopy images are shown. Invasive activity of the cells was expressed by circularity (with a value of 1 representing perfect circularity = no invasion) of each acini. Bar, 100 µm.",
    "ncbi_link": "RAB2A: 59021
RAB2A: 5862"
  },
  {
    "caption": "(b-d) MCF10.DCIS.com cells (104 cells) transfected with scrambled siRNA (siNC) or siRNA against RAB2A (siRAB2A) were plated onto 6-well dish. Representative phase contrast light microscopy images (b) and the distribution of cell numbers per cluster of the indicated cell number (c) are shown. Data are means ± SD of 10 fields (n > 60 cells/field) of independent 4 independent experiments. Bars, 100 μm. Efficacy of RAB2A gene silencing was verified by qPCR (d). Bar, 200 µm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(e) Doxycycline-inducible RAB2A-shRNA MCF10.DCIS.com cells were cultured in the absence (CTR) or presence (shRAB2A) of doxycycline for three days, and immunostained with antibodies indicated on the top (green) and DAPI (blue).",
    "ncbi_link": "RAB2A: 59021
RAB2A: 5862"
  },
  {
    "caption": "(f, g) MCF-10AneoT (f) cells were transfected with scrambled siRNA (siNC) or siRNA against RAB2A, and immunostained with antibodies indicated on the top (green) and DAPI (blue). Bars, 10 μm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(f, g) MCF10-CA1a (g) cells were transfected with scrambled siRNA (siNC) or siRNA against RAB2A, and immunostained with antibodies indicated on the top (green) and DAPI (blue). Bars, 10 μm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(h) Total cell lysates from (e), (f), and (g) were immunoblotted by anti-E-cadherin, RAB2A, and anti-actin antibodies. ***, P < 0.001, NS, not significant.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(a, b) Doxycycline-inducible RAB2A-expression MCF10.DCIS.com (a) and MCF10A (b) cells were cultured in the absence (CTR) or presence (RAB2A) of doxycycline, and immunostained with anti-RAB2A (blue), anti-E-cadherin (green), and anti-TGN46 (red) antibodies. Merged images with DAPI (magenta) are shown on the right. Bars, 10 μm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(c) CTR and RAB2AMCF10A cells (104 cells) were plated onto 6-well dish. Representative phase contrast light microscopy images (left) and the distribution of cell numbers per cluster composed of the indicated number of cells are shown. Data are means ± SD of 10 fields (n > 20 cells/field) from 3 independent experiments. Bar, 100 μm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(d) The circularity of CTR and RAB2A MCF10A cells and the percentage of cells with protrusive structure were quantified. Data are means ± SD of ten independent fields (n > 100 cells/field). n, number of cells scored for each cell population.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(e) Total cell lysate from (c) were immunoblotted with antibodies anti-E-cadherin, which recognize either an epitope in the cytoplasmic domain (IC), an epitope in the extracellular domain of mature E-cadherin (SHE78-7), respectively, or anti-RAB2A, and anti-actin. An arrow indicates the unprocessed form of E-cadherin.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(f-h) MCF10A cells were transfected with scrambled siRNA (siNC) or siRNA against Furin, and immunostained with anti-E-cadherin (green) and anti-TGN46 (red) antibodies. Merged images with DAPI (blue) are shown on the right (f). Bar, 20 μm. Total cell lysate were immunoblotted with antibodies indicated on the right (g). Efficacy of Furin silencing was verified by qPCR (h).",
    "ncbi_link": "Furin: 5045"
  },
  {
    "caption": "(i) Representative electron microscopy of Golgi stacks (arrows) of CTR and RAB2A MCF10.DCIS.com cells. Bars, 1 μm.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "(j) CTR and RAB2A MCF10A cells were transfected with Str-KDEL_SBP-EGFP-E-cadherin (green). At the indicated time points after the addition of biotin, cells were fixed, and stained without permeabilization with anti-GFP antibody, followed by Alexa568-conjugated secondary antibody (red). The cell surface and total levels of SBP-EGFP-E-cadherin at 60 min after the addition of biotin were quantified using ImageJ software on non-saturated images, and surface/total ratio was expressed as a surface GFP index (relative to control cells). Bar, 20 µm. ***, P < 0.001.",
    "ncbi_link": "RAB2A: 5862"
  },
  {
    "caption": "Left panel: Representative blots showing protein levels of YAP and phosphorylated YAP (Ser127) in control (si-Ctrl) and YAP knockdown (si-YAP) hOSEs. Protein levels were detected by Western blotting. β-Actin was used as a protein loading control. Right panel: Cell proliferation (cell number) in control (si-Ctrl) and YAP knockdown (si-YAP) hOSE cells.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Left panel: Representative blots showing protein levels of YAP and phosphorylated YAP (Ser127) in control (si-Ctrl), YAP knockdown (si-YAP), TAZ knockdown (si-TAZ) and YAP/TAZ double knockdown (si-YAP/TAZ) hOSE Cells. β-Actin was used as a protein loading control. Right panel: Cell proliferation (cell number) of control (si-Ctrl), YAP knockdown (si-YAP), TAZ knockdown (si-TAZ) and YAP/TAZ double knockdown (si-YAP&si-TAZ) hOSE cells.",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "Representative blots showing protein levels of YAP and phosphorylated YAP (Ser127) in control hOSEs (MXIV) and hOSEs expressing wild type YAP (YAP) or constitutively active YAP (YAPS127A). Cells were collected at passage 4. β-Actin was used as a protein loading control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Growth of hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at passage 4. Each bar represents mean ± SEM of four independent samples. Growth curves of hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at passage 7.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showing the morphologic changes of hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at passage 7. Scale bar: 50 µm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showing expression and location of YAP in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at passage 7. YAP was visualized using an Alexa-488 (Green) conjugated secondary antibody. Nuclei were stained with DAPI. Scale bar: 50 µm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showing SA-β-gal staining in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at passage 7. Scale bar: 50 µm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive cells in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative blots showing expression of key proteins associated with cell cycle arrest in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells analyzed using Western blotting at the 7th passage. β-Actin was used as a protein loading control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showing expression and location of phosphorylated pRB (807/811) in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at the 7th passage. Phosphorylated pRB (807/811) was visualized using an Alexa-488 (Green) conjugated secondary antibody. Nuclei were stained with DAPI (blue).",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative blots showing expression of TP53 and RB1 expression in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells in the presence or absence of HPV E6/E7 oncoproteins at the 7th passage. β-Actin was used as a protein loading control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Growth curves of hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells in the presence of HPV E6/E7 oncoproteins at the 9th passage. Each point represents mean ± SEM of four independent samples.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showing SA-β-gal staining in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells in the presence or absence of HPV E6/E7 oncoproteins at the 7th passage.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive cells in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells in the presence or absence of HPV E6/E7 oncoproteins.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "Representative images showed SA-β-gal staining in cultured primary hOSE cells in the presence or absence of HPV E6/E7 oncoproteins. Cells were collected and stained at the 13th passage. Scale bar: 25 µm. Right graph showing the ratio of SA-β-gal positive cells in P13 hOSE cells transfected with empty vectors (CTRL-P13) or vectors expressing E6/E7 oncoproteins (E6/E7-P13).",
    "ncbi_link": "E6: 25479186
E7: 25479181"
  },
  {
    "caption": "Representative blots showing the expression of YAP and RB1 in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells with or without pRB knockdown. Cells were collected at the 7th passage and protein levels were analyzed using Western blotting. β-Actin was used as a protein loading control.",
    "ncbi_link": "RB: 5925
YAP: 10413"
  },
  {
    "caption": "Growth curves of hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells after RB1 knockdown.",
    "ncbi_link": "RB1: 5925
YAP: 10413"
  },
  {
    "caption": "Representative images showing SA-β-gal staining in the hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells with or without RB1 or TP53 knockdown. Cells were collected at the 7th passage.",
    "ncbi_link": "RB1: 5925
TP53: 7157
YAP: 10413"
  },
  {
    "caption": "Representative gel photographs showing mRNA levels of LATS1 and LATS2 in hOSEs with or without LATS2 knockout. CRISPR/Cas-9 system was used to knock out LATS2 in hOSEs. LATS1/2 mRNA levels were analyzed using qRT-PCR at the fourth, ninth and thirteenth passage.",
    "ncbi_link": "CRISPR: 
Cas-9: 2777477
LATS1: 9113
LATS2: 26524"
  },
  {
    "caption": "Representative images showing the expression and location of YAP in control and LATS2 knockout hOSE cells. Cells were collected at the 4th passage and YAP expression was examined by fluorescent immunohistochemistry. YAP protein was visualized using an Alexa-488 (Green) conjugated secondary antibody. Nuclei were stained with DAPI.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative images showing YAP protein expression in the 13th passage hOSE Cells with or without LATS2 knockout. YAP protein was examined by fluorescent immunohistochemistry and visualized using an Alexa-488 (Green) conjugated secondary antibody. Nuclei were stained with DAPI (blue).",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative images showing morphological change (E) in the 13th passage (P13) hOSE cells with (LATS2 KO) or without (CTRL) LATS2 knockout.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative images showing SA-β-gal staining (F) in the 13th passage (P13) hOSE cells with (LATS2 KO) or without (CTRL) LATS2 knockout. Scale bar: 50 µm.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive cells in the control (CTRL) and LATS2-knockout (LATS2KO) P13 hOSE cells.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative blots showing expression levels of LATS1/2, CCNE1, CCND1 and YAP in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells. Cells were collected at passage four (P4) and Passage seven (P7). Actin was used as internal control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "mRNA levels of LATS1, LATS2 and YAP in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells. Cells were collected at passage seven and protein levels were analyzed using quantitative real-time PCR.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Representative gel photographs showing mRNA levels of LATS1, LATS2, and YAP in the LATS2-knockout hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells examined using semi-quantitative RT-PCR at passage seven.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Representative images showing the morphologic changes and SA-β-gal staining in control and LATS2-knockout hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells.",
    "ncbi_link": "LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive cells in the control and LATS2-knockout hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells at the seventh passage.",
    "ncbi_link": "LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Growth curves of the control and LATS2-knockout hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells.",
    "ncbi_link": "LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Representative images showing cells with ectopic expression of LATS2, which is labelled with GFP (the control is empty vectors).",
    "ncbi_link": "GFP: 
LATS2: 26524"
  },
  {
    "caption": "Relative mRNA levels of LATS1, LATS2, and YAP in the control and LATS2-expressing hOSEs at the 4th passage. Relative mRNA levels were determined with RT-PCR.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "Growth curves of hOSE cells at the 4th passage with or without ectopic expression of LATS2.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative images showing the effects of LATS2 overexpression on the morphology and growth of hOSE cells at the 9th passage.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Growth curves of control and LATS2-overexpressing hOSE cells.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive hOSEs at their 4th passage with or without ectopic expression of LATS2.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Representative images showing the effect of LATS2 on the morphology and β-galactosidase activities in cultured primary hOSE cells at the 9th passage.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "Quantitative data showing the ratio of SA-β-gal positive hOSEs at their 9th passage with or without ectopic expression of LATS2.",
    "ncbi_link": "LATS2: 26524"
  },
  {
    "caption": "mRNA levels of major components of the DREAM complex (E2F4, E2F5, RBBP4, TFDP2) in the control and LATS2-overexpressing hOSEs at the 9th passage. Relative mRNA levels were examined by real-time PCR.",
    "ncbi_link": "E2F4: 1874
E2F5: 1875
LATS2: 26524
RBBP4: 5928
TFDP2: 7029"
  },
  {
    "caption": "Growth curves of the hOSE-shRB1 cells and hOSE-shRB1-LATS2 cells at their 16th passages.",
    "ncbi_link": "LATS2: 26524
RB1: 5925"
  },
  {
    "caption": "Representative images showing cellular morphology and β-galactosidase activities in control and LATS2-overexpressing hOSEs (K). Scale Bar: 50 µm. Right bar graph (L) showing quantitative results of SA-β-gal positive cells in the hOSE-shRB1 cells and hOSE-shRB1-LATS2 cells.",
    "ncbi_link": "LATS2: 26524
RB1: 5925"
  },
  {
    "caption": "Representative images showing colony formation in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells with or without pRB knockdown or LATS2 knockout. hOSEs at the 7th passage were incubated in the growth medium in a soft agar culture system for 9 days before imaging.",
    "ncbi_link": "LATS2: 26524
RB: 5925
YAP: 10413"
  },
  {
    "caption": "Quantitative data showing colony numbers in hOSE-MXIV, hOSE-YAP and hOSE-YAPS127A cells with or without pRB knockdown or LATS2 deletion. hOSE cells at the 7th passage were incubated in the growth medium in a soft agar culture system for 9 days before counting colonies under a microscope.",
    "ncbi_link": "LATS2: 26524
RB: 5925
YAP: 10413"
  },
  {
    "caption": "Representative images showing tumorigenesis (red circle area) of hOSE-YAPS127A cells with or without pRB knockdown or LATS2 deletion. Tumors formed by hOSE-YAPS127A cells with RB1 knockdown or LATS2 deletion are shown in red circle area. Right panel showing representative tumors formed by hOSE-YAPS127A-LATS2KO and hOSE-YAPS127A-shRB1 cells. Please note that no tumor xenografts formed in hOSE-YAPS127A alone group.",
    "ncbi_link": "LATS2: 26524
RB1: 5925
RB: 5925
YAP: 10413"
  },
  {
    "caption": "Representative images showing expression of YAP, Ki67 and LATS2 in hOSE-LATS2KO-YAPS127A cell-derived tumors examined by immunohistochemistry.",
    "ncbi_link": "LATS2: 26524
YAP: 10413"
  },
  {
    "caption": "siRNA depletion of COPI increases autophagy. (A) siRNA depletion of β′-, β-, and α-COPI (top) and Sec23A and B (bottom) in 293/GFP-LC3 cells for 48 h. Decreased protein levels of the corresponding subunits is shown by immunoblots.",
    "ncbi_link": "GFP: 
α-COPI: 1314
COPI: 9276
LC3: 440738///81631///84557
Sec23A: 10484"
  },
  {
    "caption": "(B) Loss of β′-, α-, and β-COP but not subunits of COPII (Sec 23A and B) increase GFP-LC3-II. In A and B, tubulin was the loading control.",
    "ncbi_link": "GFP: 
β-COP: 1315
LC3: 440738///81631///84557
Sec 23A: 10484"
  },
  {
    "caption": "(C) GFP-LC3-positive vesicles were detectable in 293/GFP-LC3 cells after siRNA depletion of β′-, α-, and β-COP but only basal levels of GFP-LC3-positive vesicles are observed in control siRNA-depleted cells.",
    "ncbi_link": "β-COP: 1315
LC3: 440738///81631///84557"
  },
  {
    "caption": "Time course of COPI depletion shows that Golgi disperses before AVs are formed, but Golgi dispersal does not cause AV formation. (A) COPI subunits were depleted in 293/GFP-LC3 cells and analyzed 24, 36, and 48 h after addition of siRNA. Immunoblotting for β′- and α-COP confirms loss of COP subunits.",
    "ncbi_link": "GFP: 
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) After 24 h siRNA treatment, depletion of β′-COP caused morphological changes and a reduction in perinuclear population of GM130. Box indicates enlarged area.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "(D) Rab1a/b was depleted using siRNAs for 48 h. Lysates were probed with anti-Rab1 to confirm depletion.",
    "ncbi_link": "Rab1a: 5861"
  },
  {
    "caption": "(E) β′-COP or Rab1a/b were depleted as in D, and analyzed by indirect immunofluorescence using anti-GM130 and GFP fluorescence. In β′-COP panel, the asterisk indicates cells that did not show an accumulation of GFP-LC3-positive AVs.",
    "ncbi_link": "β′-COP: 9276
Rab1a: 5861"
  },
  {
    "caption": "AV formation after siRNA depletion of COPI requires Atg5 and Atg7. 293/GFP-LC3 cells were incubated with siRNA for β′-, α-COP, or control siRNA alone or combined with siRNA against Atg5 or Atg7 for 48 h, then (A) lysed and analyzed by immunoblot for Atg5, Atg7, GFP-LC3, and tubulin (loading control),",
    "ncbi_link": "Atg5: 9474
Atg7: 10533
α-COP: 1314"
  },
  {
    "caption": "Correlative light-electron microscopy analysis of GFP-LC3 puncta demonstrates they are AVs. (A) Phase, (B) fluorescent, and (C) TEM of the same field of 293/GFP-LC3 cells 48 h after siRNA depletion of α-COP. In B the image was inverted to allow better visualization of the GFP-LC3-positive structures. (D) Higher magnification of cell shown with asterisk in A and C. Top region of cell of interest is enlarged in E to show the two AVs structures indicated by arrows in B. (F and G) Higher magnification of AVs shown by arrows in E.",
    "ncbi_link": "α-COP: 1314"
  },
  {
    "caption": "Ub and p62 accumulate in α- and β′-COP-depleted 293/GFP-LC3 cells. (A) 293/GFP-LC3 cells were treated with control or β′-COP siRNA for 48 h, then fixed and labeled with anti-p62 and anti-ubiquitin antibodies for colocalization with GFP-LC3.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "(C) Cryosections from β′-COP-depleted cells were labeled with anti-Ub antibodies followed by 10-nm protein A-gold. AV, autophagosomes.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "AVs in COPI-depleted cells are not degradative. (A) Long-lived protein degradation was assessed 72 h after transfection with control or β′-COP siRNA in 293/GFP-LC3 cells. Cells were either starved of amino acids for 2 h (St) or incubated in fresh growth medium (Fed) for 2 h. The amount of protein degradation is presented as mean ± SEM.",
    "ncbi_link": "GFP: 
β′-COP: 9276
LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) siControl-treated cells and β′- and α-COP were depleted for 48 h, then incubated with Lysotracker red (50 nM) for 30 min before fixation. Merged image shows very little colocalization of GFP-LC3 AV-positive structures. Asterisk shows cell enlarged in inset",
    "ncbi_link": "α-COP: 1314"
  },
  {
    "caption": "(C) After β′- and α-COP siRNA depletion, Magic Red-RR2 (MR) was used to detect active cathepsin B in cells which were fed or starved (St) for 2 h. The intensity of MR labeling was measured in live cells by flow cytometry.",
    "ncbi_link": "α-COP: 1314"
  },
  {
    "caption": "GFP-LC3 AVs are LAMP2 positive. (A) 293/GFP-LC3 cells were incubated with control or β′- or α-COP siRNA for 48 h, fixed and labeled with anti-LAMP2 antibodies, followed by Alexa 555 anti-mouse antibodies. After COPI depletion many GFP-LC3-positive AVs are positive for LAMP2. Asterisk indicates cell enlarged in inset.",
    "ncbi_link": "α-COP: 1314"
  },
  {
    "caption": "(B) Cryosections of β′-COP-depleted cells labeled with anti-GFP (left) or anti-GFP and anti-LAMP2 (right) followed by protein A-gold as indicated. AV, autophagosomes, M, mitochondria.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "GFP-LC3-positive AVs colocalize TGN46 and early endocytotic markers after COPI depletion. (A) 293/GFP-LC3 cells were incubated with siRNA for β′-COP or control siRNA (Cont) for 48 h, processed for immunofluorescence, and labeled with antibodies for TGN46.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "Transferrin and EGF trafficking is inhibited by COPI depletion. 293/GFP-LC3 cells were treated with β′-COP siRNA or control siRNA. After 48 h cells were incubated with Alexa 555 transferrin (A) for 2 min, (B) 30 min, or (C) 30 min followed by a 30-min chase, then washed and fixed and analyzed by confocal microscopy.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "(D and E) 125I-EGF was added to HeLa cells after 48 h of siRNA depletion of β′-COP, or control siRNA for 10 min. The cells were then washed as described in the Materials and methods, and chased for 30, 60, 120, and 180 min (including 10-min incubation). (D) The amount of 125I-EGF internalized was shown as a percentage of the total 125I-EGF taken up in 10 min.",
    "ncbi_link": "β′-COP: 9276"
  },
  {
    "caption": "(A) Gene expression level of stromal activation markers COL1A1, ACTA2, SPARC, FN1 and FAP in PS-1 cells which were exposed for 72 hrs to CM from control (CM of PS-1 cells ), epithelial (blue) or mesenchymal (red) PDAC cell lines using qPCR. Values were normalized to control and n=6 per group, 3 biological replicates for each cell line. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277
FAP: 2191
FN1: 2335
SPARC: 6678"
  },
  {
    "caption": "(B) Heatmap representation of COL1A1 and ACTA2 relative gene expression levels measured with qPCR in PS-1 cells after treatment using a large cohort of PDAC cell lines and primary cell cultures 67 and 53m. Values were Log2 transformed and normalized to Suit-2 expression. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277"
  },
  {
    "caption": "(D) Gene expression levels of COL1A1 and ACTA2 in PS-1 cells after treatment using qPCR, values were normalized to control. n=3 technical replicates per group. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277"
  },
  {
    "caption": "(F) Relative gene expression levels of COL1A1 and ACTA2 in primary CAFs after treatment using qPCR, values were normalized to control. n=3 technical replicates per group. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277"
  },
  {
    "caption": "(B) Gene expression levels of COL1A1 and ACTA2 in PS-1 cells after treatment using qPCR. Data was normalized against control CM. Statistical significance was tested against unfiltered CM samples. Graph shows n=3 technical replicates of an example experiment that was performed three times. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "ACTA2: 59
COL1A1: 1277"
  },
  {
    "caption": "(E) Gene expression levels of COL1A1 in PS-1 cells after treatment using qPCR. n=3 biological replicates per group. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "COL1A1: 1277"
  },
  {
    "caption": "(B) Gene expression levels of COL1A1 in PS-1 cells after treatment using qPCR. Graph shows n=3 technical replicates of an example experiment that was performed three times. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "COL1A1: 1277"
  },
  {
    "caption": "(C) Brightfield images of PS-1 cells after 72 hrs of treatment with PANC-1 CM of pLKOctrl or shCSF1 (#560-562). Scale bar represents 100 µm.",
    "ncbi_link": "CSF1: 1435"
  },
  {
    "caption": "(D) Correlation graph of CSF1 expression in PANC-1 pLKOctrl or shCSF1 (#560-562) and how these various CM affect COL1A1 expression in PS-1 cells using qPCR, values were normalized for RPLPO expression. n=3 biological replicates for all individual experiments, error bars indicated SD. R2 and P-value were analyzed with linear regression.",
    "ncbi_link": "COL1A1: 1277
CSF1: 1435
RPLPO: 6175"
  },
  {
    "caption": "(E) Brightfield images of PS-1 cells after 72 hrs of treatment with CM of Capan-2 cells with control vector or Capan-2 cells overexpressing CSF1. Scale bar represents 100 µm.",
    "ncbi_link": "CSF1: 1435"
  },
  {
    "caption": "(F) Gene expression level of CSF1 in Capan-2 cells after transduction with control vector or overexpressing CSF1. n=3 technical replicates per group. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "CSF1: 1435"
  },
  {
    "caption": "(G) Gene expression levels of COL1A1 in PS-1 cells after treatment indicated using qPCR. Graph shows n=3 technical replicates of an example experiment that was performed three times. Data information: data are represented as mean±SD, Student's t-test.",
    "ncbi_link": "COL1A1: 1277"
  },
  {
    "caption": " Fitting of time courses (filled circles) of the translation of LepB mRNA constructs of increasing length (Appendix Fig S3) by delay-exponential functions (red lines). ",
    "ncbi_link": "LepB: 947040"
  },
  {
    "caption": " Stopped-flow time courses for translocon insertion of TM1 of EmrD (black) and EmrD(-) (blue) with mRNA constructs of varying chain length (50 to 135 aa).The FRET acceptor (Atto655) was placed at the N-terminus of the nascent peptide, the donor (Atto488) at position 111 (donor-in) of SecY. The results of global fitting are indicated (red lines). ",
    "ncbi_link": "EmrD: 948180"
  },
  {
    "caption": "(A) Schematic showing the tamoxifen  injection paradigm for tdTomato-labelling of all IFE  lineages in tail  and back. Co-expression of markers with the lineage-traced cells at 1-month post-tamoxifen. Dlx1-CrER  is shown as example in tail; Scale bar =50 µm (B) Quantification of images like those in (A) showing % tdTomato+ cells expressing indicated markers. Sox6 (black bar) was not analyzed in K14-Cre/EYFP  lineage. Error bars are SDs. P-values calculated by Student's t-test (mixed effects model) from n=2-3 mice  and 5-6 images per replicate.",
    "ncbi_link": "EYFP: 
tdTomato: 
Cr: 2777477
Cre: 2777477
Dlx1: 13390
ER: 2099
K14: 16664"
  },
  {
    "caption": "(G) Immunofluorescence  images of Sox6 staining  in noUVB (0hr) or UVB-exposed (6hrs- or 24hrs-post) mouse back skin. (H) Boxplot shows % Sox6  expressing  basal cells  quantified from images like those in (G). Central band is the mean value, the top of box indicates 25th percentile while the bottom indicates 75th percentile. Whiskers indicate minimum and maximum values in the data, with dots indicating potential outliers. Linear mixed model statistical test was used with data from 18 images from 3 biological replicates.",
    "ncbi_link": "Sox6: 20679"
  },
  {
    "caption": "A Representative fluorescent images of centrosomes  in RPE1  WT, CEP250  KO and CROCC  KO cells, without and with MT  depolymerization using Nocodazole. PCNT  was used to mark centrosomes  and DNA was stained  with DAPI. The boxes in the right-hand corner show enlargement of the centrosome  signals of the cell in the main panel. White scale bars, 5 μm. Yellow scale bars, 1 μm. B Quantification of cells with separated centrosomes (centrosome  distance > 2 μm) from RPE1  samples (A). N = 50 cells per experiment, n = 3 independent experiments. For WT with Nocodazole, N = 50 cells, n = 2 independent experiments. Bar and error represent mean and SD. Unpaired t-tests. n.s.: not significant p > 0.05, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "CEP250: 11190
CROCC: 9696"
  },
  {
    "caption": "C Representative fluorescent images of centrosomes  in HCT116  WT, CEP250  KO, and CROCC  KO, without and with MT  depolymerization using Nocodazole. γ-tubulin was used to mark centrosomes  and DNA was stained  with DAPI. The boxes in the right-hand corner show enlargements of the centrosome  signals of the cell in the main panel. White scale bars, 10 μm. Yellow scale bars, 2 μm. D Quantification of cells with separated centrosomes  (centrosome  distance > 1 μm) from HCT116  samples (C). N = 50 cells per experiment, n = 3 independent experiments. Bar and error represent mean and SD. Unpaired t-tests. ** p < 0.01, *** p < 0.001, **** p < 0.0001.",
    "ncbi_link": "CEP250: 11190
CROCC: 9696"
  },
  {
    "caption": "A-H (A, C, E, G)  Time-lapse images (4 min interval) of RPE1  WT, CEP250  KO, NIN  KO and CROCC  KO cells expressing  γ-tubulin-mRuby2  (red) as marker for the centrosomes  with and without Nocodazole  treatment. Representative still images (top rows) and kymographs  of centrosomes  (bottom rows) are shown. The DNA was marked with SPY-DNA650 (grey). White scale bars, 5 μm. Yellow scale bars, 2 μm. (B, D, F, H) Intercentrosomal distances (μm) from (A), (C), (E) and (G) were plotted over time  (n = 15 cells).",
    "ncbi_link": "CEP250: 11190
CROCC: 9696
NIN: 51199"
  },
  {
    "caption": "A Indirect immunofluorescence  analysis of Ninein  at the centrosomes  in RPE1  WT, CEP250  KO and CEP128  KO cells. CEP164  marks the mother centriole, γ-tubulin  was used as centrosome  marker. The model panel illustrates the position of the centrioles  and  centriole appendages. Scale bars: 1 μm. B STED super resolution image and model of Ninein  at the centrosome  in RPE1  WT, CEP250  KO and CEP128  KO cells. CEP164, C-Nap1  and GT335   were used to mark the mother centriole, the proximal end of centrioles, and the centriole wall, respectively. The model panel illustrates the position of the centrioles  and appendages  (colours as indicated). For WT and CEP250  KO a blue centriole  model was used for better illustration of the different positions. Scale bars: 1 μm.",
    "ncbi_link": "CEP128: 145508
CEP250: 11190"
  },
  {
    "caption": "E-H (E, G) Fluorescent images of centrosomes  in RPE1 CEP250  KO and CEP128  KO cells with the indicated siRNA depletions, without and with MT  depolymerization using Nocodazole. PCNT  or γ-tubulin was used to mark centrosomes  and DNA was stained  with DAPI. The box in the right-hand corner shows the centrosome  signals of the cell in the main panel. Scale bars in white: 5 μm. Scale bars in yellow: 1 μm. (F, H) Quantification of cells with separated centrosomes (centrosome  distance > 2 μm) for RPE1 CEP250  KO (E) and CEP128  KO (G) samples. N = 50 cells per experiment, n = 3 independent experiments. Bar and error represent mean and SD. Unpaired t-test. n.s.: not significant p > 0.05, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "CEP128: 145508
CEP250: 11190"
  },
  {
    "caption": "C Representative fluorescent images of RPE1 CEP250  KO and CEP250  KO expressing C-Nap1-HA-mNeonGreen  (CEP250  KO + CEP250). The indicated antibodies were used for indirect fluorescent analysis. Scale bars in white: 5 μm; scale bars in yellow: 1 μm. D Quantification of centrosome  separation from (C). N = 50 cells per experiment, n = 3 independent experiments. Bar and error represent mean and SD Unpaired t-test. n.s.: not significant p > 0.05, **** p < 0.0001. E Quantification of the average number (left) and length (right) of MTs  re-nucleated from the centrosomes  in (A) from RPE1  WT and CEP250  KO cells with PLK4   OE. N = 50 cells per experiment, n = 3 independent experiments. Bar and error represent mean and SD Unpaired t-test. ** p < 0.01.",
    "ncbi_link": "C-Nap1: 
HA: 
mNeonGreen: 
CEP250: 11190
PLK4: 10733"
  },
  {
    "caption": "B Fluorescent images of centrosomes  in Dox-inducible Flag-PLK4 RPE1  WT, CEP250  KO, NIN  KO and CROCC  KO cells, with and without Dox  induction. Flag-PLK4  was stained  with Flag  antibodies, PCNT  was used as centrosome  marker and DNA was stained with DAPI. The boxes on top show enlargement of the centrosome  signals of the cell in the main panel. Scale bars in white: 5 μm; scale bars in yellow: 1 μm.",
    "ncbi_link": "Flag: 
CEP250: 11190
CROCC: 9696
NIN: 51199
PLK4: 10733"
  },
  {
    "caption": "D Fluorescent images of centrosomes  in Dox-inducible Flag-PLK4 RPE1  WT, CEP250  KO, NIN  KO and CROCC  KO cells upon 48 h Dox  induction, without and with MT  depolymerization using Nocodazole. DNA was stained  with DAPI. Scale bars: 5 μm. E Quantification of the diameter of amplified centrosomes  from (D) as outlined in (A). A representative dataset from six replicates (three replicates per experiment) is shown. N = 50 cells. Dot represents the diameter of amplified centrosomes  in each cell with amplified centrosomes. The red lines represent the median. Unpaired t-test. n.s.: not significant p > 0.05, * p < 0.05, ** p < 0.01, **** p < 0.0001.",
    "ncbi_link": "Flag: 
CEP250: 11190
CROCC: 9696
NIN: 51199
PLK4: 10733"
  },
  {
    "caption": "A Representative images of live cell imaging  analysis of RPE1  WT, CEP250  KO, WT PLK4  OE and CEP250  KO PLK4  OE cells expressing LaminB1-mNeonGreen  (magenta) and  γ-tubulin-mRuby2  (green) as markers for the NE  and centrosomes, respectively. Yellow arrows indicate first NE fold. White arrows indicate first NE  discontinuation. The inlet boxes show enlargement of first NE  discontinuation. Scale bars: 5 μm.",
    "ncbi_link": "CEP250: 11190
PLK4: 10733"
  },
  {
    "caption": "C Quantification of NEBD  preparation time. WT: n = 54 cells from 6 independent experiments, CEP250  KO: n = 56 cells from 6 independent experiments, WT PLK4  OE: n = 48 cells from 7 independent experiments, CEP250  KO PLK4  OE: n = 47 cells from 8 independent experiments. D Quantification of NEBD  duration. WT: n = 54 cells from 6 independent experiments, CEP250  KO: n = 56 cells from 6 independent experiments, WT PLK4  OE: n = 48 cells from 7 independent experiments, CEP250  KO PLK4  OE: n = 47 cells from 8 independent experiments.",
    "ncbi_link": "CEP250: 11190
PLK4: 10733"
  },
  {
    "caption": "H Representative images from live cell imaging  analysis of WT, CEP250  KO, WT PLK4  OE and CEP250  KO PLK4  OE cells expressing γ-tubulin-mRuby2  (red) as a marker for the centrosomes. The DNA was marked by  SPY-DNA650 dye (cyan). Gray arrows highlight chromosome  segregation errors. Scale bars: 5 μm.",
    "ncbi_link": "CEP250: 11190
PLK4: 10733"
  },
  {
    "caption": "I Fluorescent images of RPE1  WT, CEP250  KO, WT PLK4  OE and CEP250  KO PLK4  OE cells. BUB1  and MAD1  were stained   to analyse the signal distribution or accumulation/persistence. CENP-C was used as centromere  marker, α-tubulin  to visualize the mitotic spindle and DNA was stained  with DAPI. Scale bars: 5 μm.",
    "ncbi_link": "CEP250: 11190
PLK4: 10733"
  },
  {
    "caption": "A Fluorescent image of mitotic spindles in Dox-inducible Flag-PLK4 RPE1  WT, CEP250  KO, NIN  KO and CROCC  KO cells upon 48 h Dox  induction (PLK4   OE). CW069  was used to partially inhibit HSET. DMSO  is solvent control. White scale bars: 5 μm. B Quantification of mitotic cells with  multipolar spindle from (A). N = 50 cells per experiment, n = 3 independent experiments. Bar and error represent mean and SD. Unpaired t-test. * p < 0.05, ** p < 0.01, *** p < 0.001. C Quantification of  multipolar spindle/chromosome  mis-segregation of Dox-inducible Flag-PLK4 RPE1  WT and CEP250  KO cells upon 48 h Dox  induction expressing γ-tubulin-mScarlet-I (red) as markers for the centrosomes with or without CW069  treatment. The DNA was marked with SPY-DNA650 (grey). WT PLK4   OE: nDMSO = 28 cells, nCW069 = 40 cells, CEP250  KO PLK4   OE: nDMSO = 26 cells, nCW069 = 31 cells; from 2 independent live cell experiments. Bar represents mean. Unpaired t-test. * p < 0.05.",
    "ncbi_link": "Flag: 
CEP250: 11190
CROCC: 9696
NIN: 51199
PLK4: 10733"
  },
  {
    "caption": "D Time-lapse  analysis of RPE1  WT PLK4  OE and CEP250  KO PLK4   OE cells expressing γ-tubulin-mScarlet-I (red) as markers for the centrosomes followed by 30 h siHSET. The DNA was marked with SPY-DNA650 (grey). (D) shows representative still images of live cell imaging  analysis. Scale bars: 10 μm. E Quantification of multipolar spindle/chromosome  mis-segregation from (D) in RPE1  WT PLK4   OE and CEP250  KO PLK4   OE with siControl and siHSET for 30 h. WT PLK4   OE: nsiControl = 59 cells, nsiHSET = 59 cells, CEP250  KO PLK4  OE: nsiControl = 45 cells, nsiHSET = 32 cells; from 3 independent experiments. Bar and error represent mean and SD. Unpaired t-test. * p < 0.05, ** p < 0.01.",
    "ncbi_link": "CEP250: 11190
HSET: 3833
PLK4: 10733"
  },
  {
    "caption": "(B) Quantification of free cholesterol levels in total homogenates of APP-DKO cells transiently expressing C99, C83 or AICD peptides, or treated with 5 µM Aβ42 oligomers for 16h. Cholesterol levels of WT cells are shown as a control. Lipid units are represented as molar mass over total moles of lipids analyzed (mol %). Graphs represent fold change over controls. One-way ANOVA (n = 4; * p<0.05).",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Crude membrane fractions from APP-DKO cells expressing C99WT or C99MUT were treated with 0.2% Triton-X-100, loaded onto continuous density sucrose gradients and centrifuged for 16h. Fractions from these gradients were analyzed by western blot to determine the migration of the indicated proteins [two parallel gels (bold vertical line)].",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(A) Representative confocal images of APP-DKO cells expressing GFP-tagged C99WT or C99MUT (in green) and fluorescent markers of mitochondria (MitoDsRed, in red) and ER (Sec61β-BFP, in blue), and treated with DAPT to prevent C99 cleavage. Note the different distribution of C99WT or C99MUT forms. Scale bar = 10 µm. Insets show 5X amplifications of individual (C99 in green, and mitochondria in red) and merged images. Black and white bottom panels represent the areas where C99 and mitochondria signals colocalize. Upon thresholding each channel, a mask for mitochondria was generated and the C99 channel was superimposed on the mitochondria mask, so the positive pixels found in both channels are shown in black.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(C) Representative confocal images of APP-DKO cells expressing GFP-tagged C99WT or C99MUT and ER and mitochondria markers as in (A) (upper panel). Individual zoomed single channels (middle panel) as well as areas of ER-mitochondria colocalization (bottom panel) are shown for each condition. Scale bar = 10 µm.",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(D) Quantification of ER-mitochondria colocalization per cell analyzed. Upon thresholding each channel, a mask for ER was generated and the mitochondria channel was superimposed on the ER mask, so the positive pixels found in both channels were quantified and referenced over the total area of the ER mask. The number of cells analyzed is indicated in white text within each column. Levels of ER-mitochondria colocalization in APP-WT cells are shown for reference as a dashed line. EV, empty vector. One-way ANOVA (n=3 independent experiments and 5-8 images/experiment; * p< 0.05).",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(B) Representative immunoblot to reveal C99 levels in total homogenate (TH) and MAM fractions of APP-DKO cells expressing C99WT or C99MUT before (input) and after cholesterol pull-down. Acsl4 was used as a MAM marker. Streptavidin-HRP was used to detect total biotinylation (biotin conjugated to PhotoClick cholesterol). (C) Quantification of pulled-down C99 levels versus input from the experiment in B. Two-way repeated measures ANOVA (Fraction, mutation) (n=5; * p< 0.05, ** p< 0.01). ",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "qPCR mRNA levels for YAP target genes connective tissue grow factor (CTGF) and Ankyrin Repeat Domain 1 (ANRKD1), (three experimental replicates)",
    "ncbi_link": "Ankyrin Repeat Domain 1: 27063
ANRKD1: 27063
connective tissue grow factor: 1490
CTGF: 1490"
  },
  {
    "caption": "mRNA expression of ANG in colonic tissues from normal controls (n = 25) and UC (n = 27) or CD (n = 46) patients.",
    "ncbi_link": "ANG: 283"
  },
  {
    "caption": "Ang mRNA expression in colonic tissue from 2.5% DSS-treated WT mice at indicated time point (n = 4 mice/time point). DSS: dextran sulfate sodium",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Kaplan-Meier curve of 3.5% DSS-treated Ang-deficient mice (Ang-/-, n = 14) or littermate controls (WT, n = 13).",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Body weight loss of WT and Ang-/- mice with (n = 9) or without (n = 6) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "disease activity index (DAI) of WT and Ang-/- mice with (n = 9) or without (n = 6) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Colon length of colonic section from the WT and Ang-/- mice on day 9 with (n = 9) or without (n = 6) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "serum FITC-Dextran level of colonic section from the WT and Ang-/- mice on day 9 with (n = 9) or without (n = 6) 2.5% DSS treatment. FITC-Dextran: fluorescein isothiocyanate-labeled dextran.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "representative HE staining image, and (H) histopathological score of colonic section from the WT and Ang-/- mice on day 9 with (n = 9) or without (n = 6) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Quantitative mRNA expression of cytokine genes in colonic tissue from the WT and Ang-/- mice on day 0 (n = 3) or day 9 (n = 9) during 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Soluble cytokine level in supernatant of cultured colonic tissue isolated from WT and Ang-/- mice on day 0 (n = 3) or day 9 (n = 7) during 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Body weight loss of WT→WT, Ang-/-→WT and WT→Ang-/- chimera mice with (n = 7) or without (n = 5) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "DAI of WT→WT, Ang-/-→WT and WT→Ang-/- chimera mice with (n = 7) or without (n = 5) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Ang mRNA expression in mouse lymphoid and myeloid cells; data represent two independent experiments (n = 2).",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Body weight loss of Angfl/fl and LyzMcre;Angfl/fl mice with (n = 7) or without (n = 3) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727
cre: 2777477
Lyz: 17105"
  },
  {
    "caption": "DAI of Angfl/fl and LyzMcre;Angfl/fl mice with (n = 7) or without (n = 3) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727
cre: 2777477
Lyz: 17105"
  },
  {
    "caption": "Colon length of colonic section from the Angfl/fl and LyzMcre;Angfl/fl mice on day 8 with (n = 7) or without (n = 3) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727
cre: 2777477
Lyz: 17105"
  },
  {
    "caption": "serum FITC-Dextran level, of colonic section from the Angfl/fl and LyzMcre;Angfl/fl mice on day 8 with (n = 7) or without (n = 3) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727
Lyz: 17105"
  },
  {
    "caption": "representative HE staining image, and (M) histopathological score of colonic section from the Angfl/fl and LyzMcre;Angfl/fl mice on day 8 with (n = 7) or without (n = 3) 2.5% DSS treatment.",
    "ncbi_link": "Ang: 11727
Lyz: 17105"
  },
  {
    "caption": "Quantitative mRNA expression of ANG and PLXNB2 in isolated IECs or colonic laminar propria (cLP) cells from WT mice (n = 9).",
    "ncbi_link": "ANG: 11727
PLXNB2: 140570"
  },
  {
    "caption": "Representative images showing cleaved-caspase 3 staining in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; arrows indicate cleaved-caspase 3 positive cells; two fields per colon section are quantified.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "the number of apoptotic cells in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Cell apoptotic status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Cell apoptotic status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Representative images showing Ki67 staining in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; five representative crypts per colon section are quantified.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "the number of proliferating cells per crypt in colonic section from WT or Ang-/- colitis mice (n = 3) at indicated time point; five representative crypts per colon section are quantified.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Cell-cycle status of IECs from WT or Ang-/- colitis mice (n = 5) on day 4.",
    "ncbi_link": "Ang: 11727"
  },
  {
    "caption": "Representative images showing cleaved-caspase 3 staining in colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3); arrows indicate cleaved-caspase 3 positive cells; two fields per colon section are quantified.",
    "ncbi_link": "Ang: 11727
Cre: 2777477
Lyz: 17105
Plxnb2: 140570"
  },
  {
    "caption": "the number of apoptotic cells in colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3)",
    "ncbi_link": "Ang: 11727
Cre: 2777477
Lyz: 17105
Plxnb2: 140570"
  },
  {
    "caption": "Ki67 staining and (L) the number of proliferating cells per crypt in representative colonic section from Angfl/fl and LyzMCre;Angfl/fl, or AAV-shControl- and AAV-shPlxnb2- treated colitis mice on day 4 (n = 3); five representative crypts per colon section are quantified.",
    "ncbi_link": "Ang: 11727
Cre: 2777477
Lyz: 17105
Plxnb2: 140570"
  },
  {
    "caption": "PLXNB2 expressions in HCT116 (including wild type HCT116 (HCT116WT) and ANG knockout HCT116 (HCT116KO)) and THP-1 as detected by flow cytometry analysis. The upper three dash lines represent the intensity of unstained negative control of these cells, while the solid lines represent the intensity of PLXNB2 antibody staining.",
    "ncbi_link": "ANG: 283"
  },
  {
    "caption": "THP-1-derived ANG translocating into HCT116KO through PLXNB2 in co-cultured system as showed by western blotting. Neamine, a blocker of ANG and PLXNB2 interaction; siCtrl: control siRNA; siPLXNB2-1 and siPLXNB2-2",
    "ncbi_link": "PLXNB2: 23654"
  },
  {
    "caption": "tiRNA and 5'-tiRNAAla production in HCT116KO following different treatments as indicated. ANGR66A, ANG receptor binding site variant; ANGK40I, ANG enzymatic activity null variant; BAY, inhibitor of TNF-α-induced κB kinase (IKK) phosphorylation",
    "ncbi_link": "5'-tiRNAAla: 
tiRNA: "
  },
  {
    "caption": "The effect of 5'-tiRNA knockdown or overexpression on TNF-α-induced apoptosis in ANGWT- or ANGK40I-treated HCT116KO. si5'-tiRNA: tiRNA-targeting siRNA",
    "ncbi_link": "5'-tiRNA: 
tiRNA: "
  },
  {
    "caption": "The interaction between 5'-tiRNA and cytochrome c (Cyt c) in HCT116 cells as detected by RIP.",
    "ncbi_link": "5'-tiRNA: "
  },
  {
    "caption": "Cell viability of HCT116KO following different treatments as indicated. siCtrl: control siRNA; siPLXNB2-1 and siPLXNB2-2: PLXNB2 siRNAs",
    "ncbi_link": "PLXNB2: 23654"
  },
  {
    "caption": "Detection of 47S pre-rRNA transcription level with northern blotting in HCT116KO following different treatments as indicated. siPLXNB2-1 and siPLXNB2-2: PLXNB2 siRNAs",
    "ncbi_link": "47S pre-rRNA: 
PLXNB2: 23654"
  },
  {
    "caption": "tiRNA and 5'-tiRNAAla production in IECs isolated from WT and Ang-/- colitis mice at indicated time point.",
    "ncbi_link": "5'-tiRNAAla: 
tiRNA: 
Ang: 11727"
  },
  {
    "caption": "47S pre-rRNA transcription level in IECs from WT and Ang-/- colitis mice at indicated time point.",
    "ncbi_link": "47S pre-rRNA: 
Ang: 11727"
  },
  {
    "caption": "(A) BECN1 expression of microglia from Becn1+/- and wild type mouse pups in full medium without Bafilomycin A1 (Baf) was quantified by Western blotting. Microglia from Becn1+/- mice show a signifcant reduction of BECN1 (48%) compared to microglia from wild type mice; mean ± SEM, wild type n = 3, Becn1+/- n = 7; two-tailed t-test **: p < 0.01. Blot shows representative amounts of BECN1 after various treatments.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(B) Microglia from newborn Becn1+/- and wild type mouse pups were kept for 2 h either in full medium or HBSS with or without Bafilomycin A1 (Baf). LC3 and ACTIN levels were determined by Western blot. LC3-II was significantly reduced in microglia from Becn1+/- mice after Baf treatment in full medium compared to wild type microglia; mean ± SEM, wild type n = 3, Becn1+/- n = 4; two-tailed t-test *: p < 0.05.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(C) Microglia from newborn Becn1+/- and wild type mouse pups were kept for 2 h either in full medium or HBSS with Bafilomycin A1 (Baf) and stained for endogenous LC3. Exemplary images and the quantification of LC3-positive vesicles/µm2 cell area show reduced presence of LC3-positive vesicles in microglia from Becn1+/- and induction of autophagy by HBSS; mean ± SEM, wild type n = 4, Becn1+/- n = 4, 3-5 fields per view/n and condition and 73-271 cells/n and condition; two-tailed t-test *: p < 0.05; scale bar: 20 µm",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(A, B) Microglia isolated from newborn Becn1+/- and wild type mouse pups were either non treated or treated with a pro-inflammatory stimulus (LPS followed by ATP). As additional controls cells treated only with LPS or ATP were used in (A). The concentration of the pro-inflammatory cytokines IL-1beta (A) and IL-18 (B) in the cell supernatant was determined by ELISA. Reduction of BECN1 significantly enhanced release of both cytokines after stimulation with LPS/ATP; mean ± SEM, wild type n (A/B) = 9/2, wild type LPS n = 3/0, wild type ATP n = 3/0, wild type LPS/ATP n = 9/9, Becn1+/- n = 23/5, Becn1+/- LPS/ATP n = 23/23, two-tailed t-test *: p < 0.05.",
    "ncbi_link": "Becn1: 56208
BECN1: 56208"
  },
  {
    "caption": "(E) Proteins were extracted from brains of wild type, Becn1+/-, APPPS1 and APPPS1 Becn1+/- mice at the indicated ages. IL-1beta was measured by electrochemiluminescence (MesoScale) and compared within the repective age groups. IL-1beta was significantly increased in the TBS and TX fraction; mean ± SEM, wild type: n (per age group) = 2/6/3, Becn1+/-: n = 2/5/2, APPPS1: n = 5/5/6, APPPS1 Becn1+/-: n = 7/9/6; ANOVA with Dunnett´s post hoc test with WT as control group; *: p < 0.05; **: p < 0.01.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(F) Proteins were extracted from brains of APPPS1 and of APPPS1 Becn1+/- mice at the age as indicated. Amyloid beta 1-40 and 1-42 were measured by electrochemiluminescence (MesoScale) and compared within the repective age groups. No difference in the amyloid beta load between the genotypes is apparent; mean ± SEM, APPPS1: n = 5/5/6, APPPS1 Becn1+/-: n = 7/9/6; ANOVA with Dunnett´s post hoc test with APPPS1 as control group, ns.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(A) The expression of NLRP3 protein in non treated and LPS/ATP treated wild type and Becn1+/- microglia was determined by Western blot and normalised to ACTIN. Reduction of BECN1 significantly enhanced expression of NLRP3; mean ± SEM, wild type n = 4, wild type LPS/ATP n = 9, Becn1+/- n = 4, Becn1+/- LPS/ATP n = 23; ANOVA with Tukey´s post hoc test *: p < 0.05.",
    "ncbi_link": "Becn1: 56208
BECN1: 56208"
  },
  {
    "caption": "(B) The expression of Nlrp3 mRNA in non treated and LPS/ATP treated wild type and Becn1+/- microglia was determined by qPCR. No significant differences can be detected between wild type and Becn1+/- microglia; mean ± SEM, wild type: n = 7, Becn1+/- : n = 3; ANOVA with Tukey ´s post hoc test, ns for LPS/ATP treated wild type versus Becn1+/-.",
    "ncbi_link": "Becn1: 56208
Nlrp3: 216799"
  },
  {
    "caption": "(C) LPS/ATP treated and non treated wild type and Becn1+/- microglia were immunolabeled for ASC (red) and imaged by confocal microscopy to investigate the assembly of inflammasomes. In non stimulated cells ASC is distributed diffusely in the cytoplasm (upper panels). However, after stimulation formation of inflammasomes (arrowheads) can be detected in a subpopulation of cells as well as release of inflammasomes after pyroptosis/ejection (arrow). Quantification showed a significantly increased percentage of inflammasomes in or around Becn1+/- microglia; mean ± SEM, wild type LPS/ATP n = 4, Becn1+/- LPS/ATP n = 7; two-tailed t-test *: p < 0.05; scale bar: 50 µm, insert scale bar: 10 µm.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(D) The presence of cleaved CASP1 (p10) protein in the supernatant of LPS/ATP treated wild type and Becn1+/- microglia was determined by Western blot and normalised to ACTIN. Reduction of BECN1 significantly enhanced release of CASP1; mean ± SEM, wild type LPS/ATP n = 8, Becn1+/- LPS/ATP n = 18; two-tailed t-test *: p < 0.05.",
    "ncbi_link": "Becn1: 56208
BECN1: 56208"
  },
  {
    "caption": "(A) LPS/ATP treated and non treated wild type and Becn1+/- microglia were immunolabeled for NLRP3 (green) and LC3 (red) and imaged by confocal microscopy. Stimulation resulted in the appearance of many NLRP3-containing aggregates of different sizes (arrows). In non treated cells, only a few overlapping signals with LC3-stained autophagosomes (arrowheads) are visible. Stimulated microglia however, showed multiple colocalizations of LC3 positive vesicles and NLRP3 aggregates; scale bar: 7.5 µm.",
    "ncbi_link": "Becn1: 56208"
  },
  {
    "caption": "(E) Microglia from Becn1+/- mice were transfected with scrambled siRNA or with siRNA for CALCOCO2. 6 d after transfection cells were stimulated with LPS/ATP. The expression of CALCOCO2 protein was determined by Western blot. Application of CALCOCO2 siRNA resulted in significantly reduced expression of CALCOCO2; mean ± SEM, n = 3; two-tailed t-test *: p < 0.05.",
    "ncbi_link": "Becn1: 56208
CALCOCO2: 76815"
  },
  {
    "caption": "(F) The amount of IL-1beta in the supernatant released from the cells described in (E) was determined by ELISA. Microglia with a CALCOCO2 knockdown released significantly more IL-1beta; mean ± SEM, n = 3; two-tailed t-test *: p < 0.05.",
    "ncbi_link": "CALCOCO2: 76815"
  },
  {
    "caption": "D Representative EM images of pep4Δ and pep4Δdrs2Δ strains. Black squares show a zoom-in in the vacuole. White arrowheads point to Cvt bodies.",
    "ncbi_link": "drs2: 851207
pep4: 855949"
  },
  {
    "caption": "E Representative CLEM images of drs2Δ cells. Ape1-GFP (top) correlates with a membrane-free ribosome exclusion area (middle). Black square (bottom) shows a zoom-in at the position correlating with Ape1-GFP (white arrowhead).",
    "ncbi_link": "drs2: 851207"
  },
  {
    "caption": "Ape1 processing was analyzed by western blot in the indicated strains, and normalized to the processing achieved in cells expressing wild-type Drs2 ± SD, n ≥ 3 biological replicates.",
    "ncbi_link": "Drs2: 851207"
  },
  {
    "caption": "D Ape1 processing was analyzed by western blot in the indicated strains, and normalized to the processing achieved in cells expressing wild-type Drs2 ± SD, n = 3 biological replicates.",
    "ncbi_link": "Drs2: 851207"
  },
  {
    "caption": "A Ape1 processing was analyzed by  western blot  in cells overexpressing N-terminal Drs2  (1-212 aa) and normalized to the processing achieved in cells with an empty vector ± SD, n = 3.",
    "ncbi_link": "Drs2: 851207"
  },
  {
    "caption": "A Histograms representing the mean speed of Atg9 puncta observed in wild-type, drs2Δ and drs2-5A cells. The histograms were fitted to a mixture of Gaussian distributions with two components; the percentage of each population and the means of the fitting curves are indicated on top of the plot.",
    "ncbi_link": "drs2: 851207"
  },
  {
    "caption": "B Representative images (left) and quantification (right) of the co-localization between Atg9-GFP and Ape1-mCherry (upper and middle row, respectively) in cells expressing wild-type Drs2 or drs2-5A. White arrowheads point to Ape1-mCherry clusters co-localizing with Atg9-GFP. C Values were normalized to the measurements in cells expressing wild-type Drs2. Error bars: mean ± SD, n = 3 biological replicates. Asterisks indicate significant difference as determined by a two-tailed Student's t-test (**P<0.01). Scale bar, 5µm.",
    "ncbi_link": "Drs2: 851207
drs2: 851207"
  },
  {
    "caption": "C Representative images (left) and quantification (right) of the PICT assay for the interaction of Trs85-FRB (TRAPPIII) and Atg9-GFP in cells expressing wild-type Drs2 or drs2-5A after adding rapamycin (RAP). RFP-tagged anchor and GFP-tagged prey are shown in the upper and middle row, respectively. Bottom row shows the merged images. White zoom in boxes, 0.9µm. , C Values were normalized to the measurements in cells expressing wild-type Drs2. Error bars: mean ± SD, n = 3 biological replicates. Asterisks indicate significant difference as determined by a two-tailed Student's t-test (**P<0.01). Scale bar, 5µm.",
    "ncbi_link": "Drs2: 851207
drs2: 851207"
  },
  {
    "caption": "Precursor API is trapped in a prevacuolar compartment in vps18 cells. (A) Yeast strain JSR18Δ1 with plasmid pJSR9 (vps18 ts) was grown at the permissive temperature of 26°C. Before labeling, the cells were incubated at either 26° or 38°C for 10 min. Pulse labeling was for 5 min, followed by the indicated chase times.",
    "ncbi_link": "vps18: 850840"
  },
  {
    "caption": "(B) vps18 spheroplasts were shifted to 38°C for 5 min, pulse labeled for 5 min, and then chased for either 0 or 60 min. At each time point the spheroplasts were collected by centrifugation and resuspended in PS0 buffer. The Total (T) fraction either received no treatment, was treated with 50 μg/ml proteinase K, or received proteinase K in the presence of 0.2% Triton X-100. The supernatant (S0) and pellet (P0) fractions were collected after centrifugation at 10,000 g for 5 min.",
    "ncbi_link": "vps18: 850840"
  },
  {
    "caption": "A mutant in the API propeptide causes accumulation of prAPI on a nonvacuolar compartment. (A) Spheroplasts from an ape1Δ strain containing a plasmid bearing P22L API were subjected to differential lysis in PS200 buffer. The Total (T) fraction (after differential lysis) either received no treatment, was treated with 50 μg/ ml proteinase K, or received proteinase K in the presence of 0.2% Triton X-100.",
    "ncbi_link": "ape1: 853758"
  },
  {
    "caption": "(C) ape1Δ cells containing P22L API on a plasmid were pulse labeled for 5 min, harvested by centrifugation, and subjected to a nonradioactive chase in either nitrogen-containing (SMD) or nitrogen starvation (SD-N) medium. Samples were collected at the times indicated and immunoprecipitated with API antiserum. The resulting SDS-PAGE gels were quantified using a Molecular Dynamics STORM phosphorimager.",
    "ncbi_link": "ape1: 853758"
  },
  {
    "caption": "Precursor API is trapped within a vesicle in cvt17 mutants. (A) Precursor API is in a protease-protected compartment in cvt17 mutants. THY32 (cvt17) spheroplasts were subjected to differential lysis and protease treatment in PS200 buffer as in Fig 3",
    "ncbi_link": "cvt17: 850432"
  },
  {
    "caption": "B) Precursor API is not free in the vacuolar lumen in cvt17 mutants. Differential fractionation was continued by resuspending the P200 fraction in PS0 buffer and separating the supernatant (S0) and pellet (P0) fractions by centrifugation at 10,000 g. The S0 and P0 fractions were treated with proteinase K in the presence and absence of Triton X-100 as indicated. All fractions were precipitated with 10% TCA and resolved by SDS PAGE; proteins of interest were detected by Western blotting. The positions of prAPI, mAPI, and mPrA are indicated.",
    "ncbi_link": "cvt17: 850432"
  },
  {
    "caption": "Precursor API is contained within subvacuolar vesicles in cvt17 mutants. (A) Isolated vacuoles (V) from cvt17 cells were lysed in PS0 buffer, loaded on top of an Optiprep step gradient, and centrifuged at 170,000 g for 60 min as described in Materials and Methods. Fractions VV, 0/1.06 interface; LD, 1.06 region; SV, 1.06/1.12 interface; HD, 1.12 region.",
    "ncbi_link": "cvt17: 850432"
  },
  {
    "caption": "Immuno-EM of cvt17 cells. Yeast strains SEY6210 (parental wild type) and THY32 (cvt17) were grown in YPD and prepared for microscopy as described in Materials and Methods. (A) Wild-type cells probed with antibody against mature API. (B) A cvt17 section showing a cytosolic vesicle containing prAPI probed with antibody against the API proregion. (C) A cvt17 section showing subvacuolar vesicles containing API probed with antibody against mature API. N, nucleus; V, vacuole; (arrows) API containing vesicles. Bars, 0.5 μm.",
    "ncbi_link": "cvt17: 850432"
  },
  {
    "caption": "(B). Relative values of the decreased phosphatase activities of different PTP-MEG2 mutants towards pNPP (p-Nitrophenyl phosphate) compared with wild-type PTP-MEG2. Data information: *** P<0.001: PTP-MEG2 mutants compared with the control group. Data were obtained from 3 independent experiments. N.S. means no significant difference. All the data were analyzed using one-way ANOVA, and displayed as the mean ± s.e.m. In the red column indicates that the mutation sites have greater effects on the enzyme activities toward phospho-NSF segement than the pNPP. The green column indicates that the mutation sites only have significant effects on the enzyme activity toward NSF phospho-segement but not pNPP. The white column stands for the mutants that have similar effects on pNPP and NSF phospho-segement.",
    "ncbi_link": "PTP-MEG2: 56294"
  },
  {
    "caption": "(C). Fold-change decreases in the phosphatase activities of different PTP-MEG2 mutants towards the NSF-pY83 phospho-segment compared with wild-type PTP-MEG2. Data information: *** P<0.001: PTP-MEG2 mutants compared with the control group. Data were obtained from 3 independent experiments. N.S. means no significant difference. All the data were analyzed using one-way ANOVA, and displayed as the mean ± s.e.m. In the red column indicates that the mutation sites have greater effects on the enzyme activities toward phospho-NSF segement than the pNPP. The green column indicates that the mutation sites only have significant effects on the enzyme activity toward NSF phospho-segement but not pNPP. The white column stands for the mutants that have similar effects on pNPP and NSF phospho-segement.",
    "ncbi_link": "PTP-MEG2: 56294"
  },
  {
    "caption": "(D). Statistical diagram of the quantal size in Fig. 5A and Appendix Figure S6A-D. The secretion amount of each group was standardized with respect to the control group. Data information: Green color represents the amino acids which are found to modulate foot probability based on structure analysis, and red color means amino acids which does not regulate foot probability. , * indicates PTP-MEG2 mutants overexpression group compared with the WT overexpression group. # indicates the overexpression group compared with the control group. **, P<0.01; *** P<0.001 and #, P<0.05; ##, P<0.01; ### P<0.001. N.S. means no significant difference. Data were from 6 independent experiments. All the data were analyzed using one-way ANOVA and showed as the mean ± s.e.m.",
    "ncbi_link": "PTP-MEG2: 56294"
  },
  {
    "caption": "(C). The GST pull-down assay suggested that PACSIN1, MUNC18-1, VAMP7, SNAP25, DYNAMIN1 and DYNAMIN2 directly interact with PTP-MEG2. PC12 cells were transfected with plasmids of candidate substrates, including SYN1, MUNC18-3, PACSIN1, SCAMP1, MUNC18-1, PPP3CA, STX17, VAMP7, SYT7, SYT11, SNAP25, DYNAMIN1, and DYNAMIN2 stimulated with 100 nM AngII. The tyrosine phosphorylation of these proteins was verified by specific anti-pY antibodies (Appendix Figure S8A-E). The potential substrates of PTP-MEG2 in cell lysates were pulled down with a GST-PTP-MEG2-D470A trapping mutant and then detected by Western blot. White arrow stands for Western blot band consistent with the predicted molecular weight of the potential PTP-MEG2 substrate.",
    "ncbi_link": "PTP-MEG2: 266611"
  },
  {
    "caption": "(D). Interactions of the PTP-MEG2-trapping mutants with the MUNC18-1-Y145 mutants and DYNAMIN2-Y125 mutants. PC12 cells were transfected with FLAG-MUNC18-1-Y145, FLAG-DYNAMIN2-Y125 and different mutations of the FLAG-MUNC18-1-Y145A, Y145H, Y145E or Y145F, FLAG-DYNAMIN2-Y125A, Y125E, Y125F, 24 hours before stimulation with 100 nM AngII, respectively. The cell lysates were then incubated with GST-beads-PTP-MEG2-D470A complex for 2 hours with constant rotation. The potential PTP-MEG2 substrates were pulled down by GST-beads, and their levels were examined by the FLAG antibody with Western blot.",
    "ncbi_link": "FLAG: 
DYNAMIN2: 1785
MUNC18: 6812"
  },
  {
    "caption": "(H). The MUNC18-1-Y145 mutations decreased the interaction between MUNC18-1 and SYNTAXIN1. PC12 cells were transfected with plasmid encoding SYNTAXIN-1. The proteins in cell lysates were pulled down with purified GST-beads-MUNC18-1-Y145 complex and the GST-MUNC18-1-Y145H/E/F, and detected with SYNTAXIN1 antibody. The right histogram shows the quantified protein levels. Data information * indicates MUNC18-1, mutants overexpression group compared with the WT overexpression group. # indicates MUNC18-1, overexpression group compared with the control group. *, P<0.05; **, P<0.01; *** P<0.001 N.S. means no significant difference. Data were from 3 (H) independent experiments. All the data were analyzed using one-way ANOVA, and showed as the mean ± s.e.m.",
    "ncbi_link": "SYNTAXIN-1: 6804
MUNC18: 6812"
  },
  {
    "caption": "(E). Relative phosphatase activities of different PTP-MEG2 mutants towards the MUNC18-1-pY145 phospho-segment compared with wild-type PTP-MEG2. (F). Relative phosphatase activities of different PTP-MEG2 mutants towards the DYNAMIN 2-pY125 phospho-segment compared with wild-type PTP-MEG2.Data information: (E, F) Residues are coloured according to Figure 8B. (E, F), * P<0.05, ** P<0.01, *** P<0.001: PTP-MEG2 mutants compared with the control. N.S. means no significant difference. Data were obtained from 3 independent experiments. **, P<0.01; *** P<0.001 and ## P<0.01; ### P<0.001. N.S. means no significant difference. Data were obtained from 10 cells in each group of 6 independent experiments. . All the data were analyzed using one-way ANOVA and showed as the mean ± s.e.m.",
    "ncbi_link": "PTP-MEG2: 266611"
  },
  {
    "caption": "(B) Representative time-course of 2 mmol/L phosphate on calcification of LmnaG609G/+ VSMCs (up). Calcification was visualized with Alizarin red. Representative microscopic images (10x; scale bar: 100 µm) showing calcification of treated and untreated LmnaG609G/+ VSMCs (down).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(C-F) Measures of calcium in treated living LmnaG609G/+ VSMCs (C), treated fixed LmnaG609G/+ VSMCs (D), untreated living LmnaG609G/+ VSMCs (E), and untreated fixed LmnaG609G/+ VSMCs (F).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(A) Magnesium intake in 34-week-old untreated and treated LmnaG609G/+ mice (n=16).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(B) Plasma magnesium concentration in 34-week-old untreated and treated LmnaG609G/+ mice (n=16).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(C) Calcium content of aortas obtained from 34-week-old wild-type mice and untreated and treated LmnaG609G/+ mice (n=20).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(D) Body masses of 34-week-old untreated and treated LmnaG609G/+ mice.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(E) Kaplan-Meier graph for untreated and treated LmnaG609G/+ mice (n=16).",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(F) Representative photographs of 40-wk-old wild-type, untreated and treated LmnaG609G/+ mice.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "(A) ATP concentration in liver homogenates obtained from 34-week-old wild-type, untreated or treated LmnaG609G/+ mice.",
    "ncbi_link": "Lmna: 16905"
  },
  {
    "caption": "A IMR90 ER:RasV12 primary fibroblasts were cultured in the presence of EtOH  (proliferating) or 100nM 4OHT  (for 6-8days to induce RasV12 expression and oncogene-induced senescence, OIS). mRNA levels of 4OHT  cells, normalised to PUM1  and presented relative to EtOH  control. (n=4 independent experimental repeats). Data information: All graphs show individual data points, mean and error bars represent standard deviation. All data are analysed by 2-tailed, nonpaired Student's t-test (* <0.05, ** <0.01, *** <0.001)",
    "ncbi_link": "ER: 2099
Ras: 3265
PUM1: 9698"
  },
  {
    "caption": "A Fibroblasts  stably expressing GFP-TFEB  were treated 4OHT  to induce senescence (or EtOH  control). Cells were lysed and subject to  Western blotting for antibodies as indicated. B Quantification of A. (n=4 independent experimental repeats) C Quantification of A. (n=3 independent experimental repeats) Data information: All graphs show individual data points, mean and error bars represent standard deviation. B and C: analysed by 2-tailed, unpaired T-Test * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "GFP: 
TFEB: 7942"
  },
  {
    "caption": "D Western blot of GFP immunoprecipitation  of control (EtOH) and senescent (4OHT) cells expressing GFP  or GFP-CDK4  and FLAG-TFEB.",
    "ncbi_link": "FLAG: 
GFP: 
CDK4: 1019
TFEB: 7942"
  },
  {
    "caption": "H Fibroblasts  stably expressing GFP-TFEB  were transduced with p16  shRNA simultaneously with induction of senescence by 4OHT. Cells were lysed and subject to Western blotting. I Quantification of H (n=4 independent experimental repeats). Data information: All graphs show individual data points, mean and error bars represent standard deviation. All other panels analysed by one-way ANOVA with Tukey's multiple comparison test (* <0.05, ** <0.01, *** <0.001)",
    "ncbi_link": "GFP: 
p16: 1029
TFEB: 7942"
  },
  {
    "caption": "J Fibroblasts   were transduced with p16  shRNA simultaneously with induction of senescence by 4OHT. Cells were lysed and subject to Western blotting. K, L Quantification of J (n=3 independent experimental repeats) Data information: All graphs show individual data points, mean and error bars represent standard deviation. All other panels analysed by one-way ANOVA with Tukey's multiple comparison test (* <0.05, ** <0.01, *** <0.001)",
    "ncbi_link": "p16: 1029"
  },
  {
    "caption": "M Fibroblasts  were transduced with p16  shRNA simultaneously with induction of senescence  by 4OHT. Cells were fixed and immunostained  with antibodies against p62  and Lamp2, Scale bar: 20µm.",
    "ncbi_link": "p16: 1029"
  },
  {
    "caption": "O Fibroblasts  were transduced with p16  shRNA simultaneously with induction of senescence  by 4OHT. Cells were incubated with serum-free media overnight which was collected and subject to ELISA  analysis for  IL-6 (n=3 independent experimental repeats) Data information: All graphs show individual data points, mean and error bars represent standard deviation. All other panels analysed by one-way ANOVA with Tukey's multiple comparison test (* <0.05, ** <0.01, *** <0.001)",
    "ncbi_link": "p16: 1029"
  },
  {
    "caption": "(d) Effects of siRNA-mediated knockdown of Atg3 or Atg7 on cell death in the absence or presence of C18PC were determined and compared to effects of transfection with Scr siRNAs (controls) using Trypan blue exclusion assay.",
    "ncbi_link": "Atg3: 64422
Atg7: 10533"
  },
  {
    "caption": "(e) Roles of C18PC in the regulation of lethal autophagy were assessed after treatment of MEFs isolated from wild-type (ATG5+/+) and ATG5−/− knockout mice with C18PC. Control cells were treated with vehicle.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(f) Effects of C18PC on caspase-dependent or caspase-independent cell death were determined in MEFs isolated from Bax−/− Bak−/− or Casp3−/− Casp7−/− mice and from wild-type (Bax+/+ Bak+/+) or Casp3+/− Casp7+/− mice, used as controls. Data shown are an average of at least three experiments ± s.d. (*P 0.05).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Casp3: 12367
Casp7: 12369"
  },
  {
    "caption": "(a) Effects of expression of wild-type (WT) CerS1 and its catalytically inactive V5-tagged mutant (Mut), which cannot generate C18-ceramide, on the formation of LC3B-II were determined by western blotting (+/− tet). Successful induction of wild-type and mutant CerS1 expression was confirmed using anti-V5. β-actin was used as a loading control. Full blots can be found in Supplementary Figure 13.",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(b) Generation of endogenous C18- and C18:1-ceramides in response to wild-type CerS1 and mutant CerS1 induction was measured by LC/MS/MS.",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(c) Effects of wild-type CerS1 and C18-ceramide induction (+ tet) on GFP and LC3B-GFP lipidation were visualized using confocal microscopy and compared to effects of noninduced controls (− tet). Scale bars, 10 μm",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(d) The effects of induction of wild-type CerS1 and C18-ceramide and catalytically inactive mutant CerS1 (+ tet) in the regulation of mitochondrial function were assessed by measuring OCR using the SeaHorse and compared to roles of noninduced controls (− tet).",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(e) Targeting mitochondria with autophagolysosomes in the absence (− tet) or presence (+ tet) of wild-type CerS1 and C18-ceramide was visualized by colocalization of MTG and LTR using confocal microscopy. Scale bars, 10 μm.",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(f) Effects of wild-type and mutant CerS1 (−/+ tet) on ATP generation.",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(g) Effects of wild-type CerS1 (−/+ tet) on ATP generation in the absence (control shRNA) or presence of shRNA-mediated knockdown of LC3B. Data shown are an average of at least three experiments ± s.d. (*P 0.05).",
    "ncbi_link": "CerS1: 10715
LC3B: 81631"
  },
  {
    "caption": "(a) Subcellular localization of ceramide, generated by wild-type CerS1 induction (+ tet), was visualized in mitochondria by colocalization of ceramides and mitochondria with anti-ceramide and anti-Tom20, respectively, using confocal microscopy.",
    "ncbi_link": "CerS1: 10715"
  },
  {
    "caption": "(b,c) Mitochondrial (Mito) targeting of LC3B-II and C18-ceramide, generated by induction of wild-type CerS1 (b), and that of the products of the catalytically inactive mutant CerS1 (+ tet) (c) was visualized by colocalization of ceramide (Cer; green), CFP-LC3B (blue) and MTR using anti-ceramide and confocal microscopy. Noninduced cells (− tet) were used as controls. Scale bars, 10 μm.",
    "ncbi_link": "Mito: 
CerS1: 10715"
  },
  {
    "caption": "(a) Binding of Flag-tagged wild-type LC3B and LC3BI35A, LC3BF52A or LC3BG120A with endogenous C18-ceramide (C18-Cer), generated in response to wild-type CerS1 induction (left) or exogenous C18-Pyr-Cer (right), was measured using LC/MS/MS after pulldown using anti-Flag-conjugated beads. Data shown are an average of at least three experiments ± s.d. (*P 0.05).",
    "ncbi_link": "CerS1: 10715
LC3B: 81631"
  },
  {
    "caption": "(b) Effects of CerS1 and C18-ceramide induction on the lipidation of Flag-tagged wild-type, LC3BI35A, LC3BF52A and LC3BG120A proteins were examined by western blotting. Noninduced cells (− tet) were used as controls. β-actin was used as a loading control. Full blots can be found in Supplementary Figure 13.",
    "ncbi_link": "CerS1: 10715
LC3B: 81631"
  },
  {
    "caption": "(c) Effects of siRNA-mediated knockdown of p62, NIX and Drp1 on OCR in the absence or presence of CerS1 and C18-ceramide induction were measured using the SeaHorse. Data shown are an average of at least three experiments ± s.d. (*P 0.05).",
    "ncbi_link": "NIX: 665
CerS1: 10715
Drp1: 10059
p62: 8878"
  },
  {
    "caption": "(d) Effects of siRNA-mediated knockdown of Drp1 (lower left and right) on the localization of ceramide within mitochondrial membranes were visualized using the colocalization of anti-ceramide (red) and anti-Tom20 (green) under confocal microscopy, in the absence (upper and lower left) or presence (upper and lower right) of CerS1 and C18-ceramide induction (−/+ tet) compared to Scr siRNA-transfected controls (upper left and right). Scale bars, 10 μm in a and d. Enlarged images are shown in boxed areas in d.",
    "ncbi_link": "CerS1: 10715
Drp1: 10059"
  },
  {
    "caption": "(a,b) Roles of shRNA-mediated stable knockdown of endogenous LC3B expression in the regulation of mitochondrial function (a) or UM-SCC-22A xenograft-derived tumor growth (b) in the absence or presence of wild-type CerS1 and C18-ceramide induction (−/+ tet) were determined using the SeaHorse or measurement of tumor volumes in the flanks of SCID mice (n = 6 per group), respectively. Data shown are an average of at least three experiments ± s.d. (*P 0.05).",
    "ncbi_link": "CerS1: 10715
LC3B: 81631"
  },
  {
    "caption": "B. Instability of BU-1 expression in timeless cells. FACS plots of wild type and timeless (clone 1) DT40 cells stained with anti-Bu-1 conjugated with phycoerythrin. Each line represents the Bu-1 expression profile of an individual clonal population. Unstained controls are shown in blue.",
    "ncbi_link": "timeless: 101751192"
  },
  {
    "caption": "C. Fluctuation analysis for Bu-1 loss in wild-type DT40 cells and two independent timeless clones generated by CRISPR-Cas9 targeting (clones 1 and 2; , timeless (clone 1) complemented by expression of human Timeless cDNA and a timeless mutant on a background in which the endogenous +3.5 G4 has been deleted (ΔG4)",
    "ncbi_link": "Bu-1: 
Cas9: 57852564
timeless: 101751192
Timeless: 8914"
  },
  {
    "caption": "D. Fluctuation analysis for Bu-1 loss in DT40 wild-type and tipin cells.",
    "ncbi_link": "Bu-1: 
tipin: 415548"
  },
  {
    "caption": "Fluctuation analysis for the generation of Bu-1 loss variants. Top to bottom: wild type, timeless (clone 1), a timeless mutant (timeless ∆C) generated by CRISPR-Cas9 targeting exon 16 which truncates the protein removing the CTD containing both the DBD and the PARP binding domains. Then, complementation of timeless#1 with human Timeless (hTim), hTim∆816-1208 (lacking both the DBD and PBD), hTim∆816-965 (lacking the DBD) and hTim[1:1000], lacking the PBD. At least two independent fluctuation analyses were performed with 24-36 individual clones each cell line per repeat.",
    "ncbi_link": "Bu-1: 
Cas9: 57852564
timeless: 101751192
Tim: 8914
Timeless: 8914"
  },
  {
    "caption": "B. Fluctuation analysis for Bu-1a loss in wild-type DT40 cells, two independent ddx11 clones generated by CRISPR-Cas9 targeting (clones 1 and 2) and one ddx11 clone generated by conventional homologous recombination gene targeting (clone 3). Each symbol represents the percentage of cells in an individual clone expanded for 2-3 weeks that have lost Bu-1ahigh expression.",
    "ncbi_link": "Bu-1a: 
Cas9: 57852564
ddx11: 418144"
  },
  {
    "caption": "C. Fluctuation analysis for Bu-1a loss variant generation in wild-type cells, ddx11 (clone 1) cells, ddx11 (clone 1) complemented by expression of chicken DDX11 WT cDNA, ddx11 (clone 1) complemented by expression of helicase-dead form of chicken DDX11 (K87A) cDNA, and a ddx11 clone generated in cells in which the endogenous +3.5 G4 has been deleted (ΔG4).",
    "ncbi_link": "Bu-1a: 
ddx11: 418144
DDX11: 1663"
  },
  {
    "caption": "D. Fluctuation analysis for Bu-1 loss in two independent timeless/ddx11 double-mutant clones (#1 and #2), ddx11 expressing DDX11KAK and fancj and fancj/ddx11 double-mutants. Fluctuation analyses for wild type, timeless #1 and ddx11 #1 are shown for comparison.",
    "ncbi_link": "Bu-1: 
fancj: 417642
ddx11: 418144
DDX11: 1663
timeless: 101751192"
  },
  {
    "caption": "A. Growth curves for DT40 wild type, ddx11, timeless and ddx11/timeless cells, with and without 4 μM pyridostatin (PDS). Cells were seeded at 5 x104 cells/ml on day 0 and the viable cells were counted each 24 h for 4 days. Bars represent SD of two independent experiments performed in duplicate. Doubling times (DMSO): WT 13 hours, timeless 18 hours, ddx11 16 hours, ddx11/timeless 24 hours. Doubling times (PDS): WT 13.6 hours, timeless 27 hours, ddx11 25.7 hours, ddx11/timeless 47.5 hours.",
    "ncbi_link": "ddx11: 418144
timeless: 101751192"
  },
  {
    "caption": "B. DDR signalling detected by phosphorylation of histone H2AX (γ-H2AX) by flow cytometry in untreated cells or cells exposed to 4 μM PDS for 3 days. Pale histogram, untreated; dark histogram, treated; black dotted line, positive control cells treated with 0.1 µM cisplatin, also for 3 days. C. Quantification of γ-H2AX in DT40 wild type, ddx11, timeless and ddx11/timeless cells treated with 4 μM PDS for 3 days. The central band represents the median, the box the 25th - 75th centile and whiskers the minimum to maximum range of three independent experiments performed in duplicate. ",
    "ncbi_link": "ddx11: 418144
timeless: 101751192"
  },
  {
    "caption": "A. Correlation of magnitude and direction of change of genes dysregulated (relative to wild type) in timeless vs. ddx11 DT40 cells. rs (Spearman rho) is shown for each correlation.",
    "ncbi_link": "ddx11: 418144
timeless: 101751192"
  },
  {
    "caption": "B. Genes dysregulated in timeless, ddx11 and fancj mutants have a higher density of G4s around their TSS. Cumulative fraction of the genes dysregulated in timeless (red), ddx11 (blue) and fancj (green) containing n (x-axis) G4 motifs within 1.5kb of the TSS compared with all genes (black).",
    "ncbi_link": "fancj: 417642
fancj: 83990
ddx11: 418144
timeless: 101751192"
  },
  {
    "caption": "C. Metagene analysis showing G4 frequency around the TSS of genes dysregulated (up or down) in timeless (left panel), ddx11 (centre panel) and fancj (right panel) compared with all genes (black line). G4 frequency is calculated separately for coding (above the x-axis) and template strands (below the x-axis).",
    "ncbi_link": "fancj: 417642
ddx11: 418144
timeless: 101751192"
  },
  {
    "caption": "(f) BJAB and Jurkat cells expressing control or Atg5 shRNA were treated with Fas ligand (15 ng ml−1) or TRAIL (12.5 ng ml−1) for 24 h (same technical replicate as d). Cells were then re-plated at low density and allowed to recover for 5-6 days, and then assayed for viability (percentage of no ligand control, mean ± s.e.m., n = 3 wells, *P = 0.0089). Atg7 knockdown data were not included for long-term viability owing to the growth suppressive effect of Atg7 knockdown in the absence of drug treatment. Uncropped images of blots are shown in Supplementary Fig. 6.",
    "ncbi_link": "Atg5: 9474"
  },
  {
    "caption": "(e,f) BJAB and Jurkat cells were transduced with control, Atg5, Atg7 or Vps34 shRNA lentiviruses, followed by three days of puromycin selection. Cells were then treated with Fas ligand (1.25 ng ml−1) or TRAIL (1.25 ng ml−1) for 24 h and viability was assessed by MTS (e; percentage of control (no ligand), mean ± s.e.m., n = 3 wells, *P = 1.4×10−6, **P = 2.3×10−5, ***P = 3.9×10−5, §P = 9.2×10−6, §§P = 3.4×10−6, §§§P = 1.7×10−5). Immunoblots demonstrate Atg5, Atg7 and Vps34 knockdown, autophagy inhibition and altered Fap-1 levels. The blots are separated because different exposures were required to detect the proteins in one cell line without overexposing the lanes for the other; the Fap-1 blot is not separated to demonstrate the lack of Fap-1 protein in Type II Jurkat cells (f). Fap-1 blots (b,c,f) were run on separate gels owing to the quantity of protein required for detection (see Methods). Uncropped images of blots are shown in Supplementary Fig. 6.",
    "ncbi_link": "Atg5: 9474
Atg7: 10533
Vps34: 5289"
  },
  {
    "caption": "(a,b) BJAB and Jurkat cells expressing the indicated Fap-1 wild-type (WT) and catalytically inactive (ΔCD) constructs were treated with chloroquine (BJAB, 20 μM; Jurkat, 10 μM) for 16 h followed by Fas ligand (BJAB, 1.5 ng ml−1; Jurkat 15 ng ml−1) for 24 h. Cell viability was determined by MTS (a; percentage of control (no ligand), mean ± s.e.m., n = 3 wells, *P = 2.7×10−4, **P = 2.4×10−5, ***P = 0.0024). Cell lysates were blotted and probed with the indicated antibodies (b).",
    "ncbi_link": "Fap-1: 5783"
  },
  {
    "caption": "c-e) BJAB cells expressing control or Fap-1 shRNAs were treated with 20 μM chloroquine for 16 h followed by Fas ligand (12.5 ng ml−1) or TRAIL (25 ng ml−1) for 24 h; cell viability was then determined by MTS (c; percentage of control (no ligand), mean ± s.e.m., n = 3 wells, *P = 4.8×10−6, **P = 8.1×10−5, ***P = 8.0×10−4, §P = 0.013, NS P>0.05).",
    "ncbi_link": "Fap-1: 5783"
  },
  {
    "caption": "a,b) Cell viability was determined by MTS assay following Fas ligand (4 ng ml−1) treatment in BJAB cells expressing control or p62 lentiviral shRNAs (a; percentage of control (no ligand), mean ± s.e.m., n = 3 wells, *P = 3.2×10−5, **P = 1.8×10−6). Immunoblots confirm p62 depletion and Fap-1 levels (b).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(B) Lineage tracing of the anagen matrix from β-actin-CreER:Confetti, 7 days after induction with either a high dose of tamoxifen (TM) (top) or low dose (bottom) for single cell clonal lineages.",
    "ncbi_link": "Cre: 
ER: 13983///13982"
  },
  {
    "caption": "(D) images (D') for Gata6 inducible knockout (iKO) and wild type (WT) mice over time, showing the loss of Gata6 (red) from the hair follicle. Scale bars: 30 m.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(B-G) Gata6 WT and iKO skin after 3 days after TM induction and 12 hours after BrdU labeling or 5 days after TM induction and 2 days after BrdU labeling stained with markers as indicated in corresponding color.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(A) Hair follicles exhibit immunostaining signal for DNA damage marker H2A.X (red) and apoptosis marker Caspase3 (green) as early as one day after Gata6 iKO induction. Top panel shows a section of UV irradiated epidermis as a positive control for DNA damage. Note that Caspase 3 is not expressed in the H2A.X cells of the epidermis but is found in some iKO hair follicle matrix cells. Right panels show single color images as indicated at top (B) Quantification (average SD) of the percentage of apoptotic cells per matrix as determined by counting of Caspase3+ cells (n=50 follicles from 3 mice per group) (C) Quantification (average SD) of the percentage of DNA damaged cells per matrix as determined by counting of H2A.X+Caspase3- cells (n=50 follicles from 3 mice per group).",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(A) Colony formation of WT and TM induced Gata6 iKO keratinocytes stained with hematoxylin. Primary keratinocytes were isolated from induced iKO newborn mice, plated on feeder cells, and stained with hematoxylin at day 7 after plating (top). Phase contrast images of cells are shown below. Scale bars: 30 m. (B) Quantification of colony formation from (A), average SD from n=3 mice in each genotype.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(C) Western blot of WT and iKO cultured keratinocytes after 0 or 6 hours of tamoxifen induction, blotted with actin and Gata6 antibodies, show a decrease in Gata6 protein levels after 6 hours.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(D) Phase contrast images of WT and Gata6 iKO keratinocytes 3 days after induction with TM (n > 3 per genotype).",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(I-J) FACS cell cycle profiles and quantification show that Gata6 iKO keratinocytes show decreased proliferation and G2-M arrest.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(I-J) FACS cell cycle profiles and quantification show that Gata6 iKO keratinocytes show decreased proliferation and G2-M arrest. (J) Quantification of FACS cell cycle analysis represent average SD (n=3 per genotype). *Unpaired t-test P-values: G1 = 0.03, S = 5x10-4, G2-M = 7x10-4.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(B) qRT-PCR validation of candidate genes selected from RNA-seq analysis using RNA from cultured cells (average SD, n=4). *Unpaired t-test P-values: Edaradd=0.03, Apcdd1=0.005, Gls2=7x10-5, Ppargc1b=3x10-4, Rab17=2x10-5, Foxn1=0.03. Mann-Whitney U test P-values: Edaradd=0.06, Apcdd1=0.03, Gls2=0.03, Ppargc1b=0.03, Rab17=0.03, Foxn1=0.03. (C) Table summarizing selection of candidate genes from (B). Genes were selected based on known function or skin phenotype related to Gata6 iKO phenotype.",
    "ncbi_link": "Apcdd1: 494504
Edaradd: 171211
Foxn1: 15218
Gata6: 14465
Gls2: 216456
Ppargc1b: 170826
Rab17: 19329"
  },
  {
    "caption": "(H) qRT-PCR of selected genes found to be overlapping between Gata6 iKO and Eda transgenic analyzed in Gata6 WT and iKO keratinocytes (average SD, n=4). *Unpaired t-test P-values: Mcm3=0.001, Mcm6=0.02, Mcm10=0.04, Exo1=0.02, Pold1=0.02. Mann-Whitney U test P-values: Mcm3=0.03, Mcm6=0.03, Mcm10=0.03, Exo1=0.03, Pold1=0.06.",
    "ncbi_link": "Eda: 13607
Exo1: 26909
Gata6: 14465
Mcm10: 70024
Mcm3: 17215
Mcm6: 17219
Pold1: 18971"
  },
  {
    "caption": "(B) qRT-PCR confirmation of the change in Edaradd mRNA expression in-vivo from mouse whole skin (average SD, 1d n=3, 2d n=4). *Unpaired t-test P-values: 1d = 0.02, 2d = 0.05. Mann-Whitney U test P-values: 1d=0.06, 2d=0.03.",
    "ncbi_link": "Edaradd: 171211"
  },
  {
    "caption": "(C) ChIP-qPCR for Gata6 at three conserved binding sites within the Edaradd promoter. GAPDH served as a negative control. Binding site 1, 2, and 3 are located 50 bp, 1 kb, and 1.5 kb upstream of the transcription start site, respectively (average SD, n=4). *Unpaired t-test P-values GAPDH=0.4, 1=0.002, 2=0.8, 3=0.2. Mann-Whitney U test P-values: GAPDH=0.3, 1=0.06, 2=0.9, 3=0.2.",
    "ncbi_link": "Edaradd: 171211"
  },
  {
    "caption": "(E-F) Staining for Edaradd and quantification show decrease in Edaradd protein levels in the matrix of Gata6 iKO. *Unpaired t-test P-value = 3.5x10-14. n=100 follicles from 3 mice per genotype.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(G-H) Staining for pNF-B and quantification show decrease of active NF-B in the Gata6 iKO matrix. *Unpaired t-test P-value = 2.2x10-16. n=50 follicles from 3 mice.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(I) Rescue of Gata6 iKO keratinocyte growth by transfection with pGata6 or pEdaradd. Cell plates of keratinocytes are stained with Rhodanile Blue (n=3 cell lines each).",
    "ncbi_link": "Edaradd: 171211
Gata6: 14465"
  },
  {
    "caption": "(J) Quantification of H2A.X in cells stably transfected with pMock, pGata6, or pEdaradd plasmids, followed by induction with TM for 6 hours (average SD, n=4 with > 500 cells counted per condition). *Unpaired t-test P-values = 2x10-4 (iKO pGata6 vs pMock), 2x10-4 (iKO pEdaradd vs pMock).",
    "ncbi_link": "Edaradd: 171211
Gata6: 14465"
  },
  {
    "caption": "(K) qRT-PCR analysis of Mcm10 expression in pMock, pGata6, and pEdaradd WT and iKO expressing cells (average SD, n=4). *Unpaired t-test P-values: 8x10-4 (iKO pGata6 vs pMock), 0.03 (iKO pEdaradd vs pMock). Mann-Whitney U test P-values: 0.03 (iKO pGata6 vs pMock), 0.03 (iKO pEdaradd vs pMock).",
    "ncbi_link": "Edaradd: 171211
Gata6: 14465
Mcm10: 70024"
  },
  {
    "caption": "(a-d) RNAi-mediated knockdown of dUTX inhibits ecdysone-induced apoptotic cell death. SL2 cells were treated with two independent dsRNAs to dUTX or a control gene (GFP) for 48 h and cell death was induced with 10 μM ecdysone for 24 h. (a) The cell viability was assayed by trypan blue staining. Data are mean from three independent experiments, with error bars representing s.e.m. *P0.05 (Student's t-test). (b) Cell count and viability assay using Muse (Millipore, USA). Data are mean from three independent experiments, with error bars representing s.d. *P0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
dUTX: 34377"
  },
  {
    "caption": "(a-d) RNAi-mediated knockdown of dUTX inhibits ecdysone-induced apoptotic cell death. SL2 cells were treated with two independent dsRNAs to dUTX or a control gene (GFP) for 48 h and cell death was induced with 10 µM ecdysone for 24 h. (c) Caspase activity was measured from total cell lysate on DEVD-AMC, represented as fold increase relative to control RNAi. Data are mean from three independent experiments, with error bars representing s.e.m. *P0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
dUTX: 34377"
  },
  {
    "caption": "(a-d) RNAi-mediated knockdown of dUTX inhibits ecdysone-induced apoptotic cell death. SL2 cells were treated with two independent dsRNAs to dUTX or a control gene (GFP) for 48 h and cell death was induced with 10 μM ecdysone for 24 h. (d) The level of knockdown of dUTX was quantificated by qPCR and normalized against ribosomal protein rp49. Relative dUTX expression levels following knockdown using the two independent dsRNA are shown (n=3) with error bars representing s.d. *P0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
rp49: 
dUTX: 34377"
  },
  {
    "caption": "(a,b) dUTX directly interacts with ecdysone receptor (EcR/Usp). (a) GST and GST-dUTX-NR containing the nuclear hormone domain were used in pull-down experiments with 35S-labelled EcR and Usp in the presence of ethanol control (−) or 10 μM ecdysone (+). The GST input proteins are shown in Coomassie Brilliant blue-stained gel, GST is labelled with arrow head and dUTX-NR with an asterisk. The EcR and Usp inputs are shown labelled with arrows.",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(a,b) dUTX directly interacts with ecdysone receptor (EcR/Usp). (b) Immunoprecipitation (IP) of EcR and dUTX in SL2 cells. Cells were transfected with HA-dUTX and the cell lysates were immunoprecipitated using anti-HA or a control IgG isotype antibody. The immunoprecipitates were analysed by western blotting using the anti-EcR and anti-HA antibodies.",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(c) Colocalization of dUTX and EcR on salivary gland polytene chromosomes. Immunostaining of salivary glands polytene chromosome prepared from third instar larvae expressing FLAG-dUTX with dUTX (green) and EcR (red), with Hoechst-stained DNA (blue). Arrows indicate examples of colocalized bands. No signal was detected when immunostaining with secondary antibody only. Scale bar represent 5 μm.",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(a) Histology analysis of paraffin sections at 14 h and 24 h RPF shows intact salivary glands present in dUTX1 compared with control at 24 h RPF. Ovals indicate the position of salivary glands and fragments. Scale bar represent 50 μm. Quantification of the salivary gland phenotypic data was at 24 h RPF.",
    "ncbi_link": "dUTX1: 34377"
  },
  {
    "caption": "(b,c) Caspase staining and activity are reduced in dUTX1 salivary glands at 14 h RPF. (b) Cleaved caspase-3 antibody (green) and Lamin antibody (red) staining are shown in control and dUTX1 salivary glands at 14 h RPF. Scale bar represents 50 μm. (c) Caspase activity was measured from 14 h RPF control and dUTX1 salivary glands using DEVD-AMC as a substrate. Data are mean from three independent experiments each using at least 20 salivary glands from control and dUTX1 for preparing cell extracts. The error bars represent s.e.m. *P-value0.05 (Student's t-test).",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(d) Autophagy puncta examined using mCherry-Atg8a (red) and nuclei stained with Hoechst (blue). Scale bar represents 100 μm. The quantitation of the mCherry-Atg8a puncta as the mean fluorescent pixel intensity per cell (control n=242, dUTX1 n=224), with error bars representing s.e.m. *P-value0.05 (Student's t-test).",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(a) Levels of dark, dronc, drice and rpr transcripts were measured from third instar larvae (L3), 6 h and 14 h RPF salivary glands from control (blue) and dUTX1 (red) by qPCR and expressed relative to the internal control gene rp49.",
    "ncbi_link": "rp49: 
dark: 36914
drice: 43514
dronc: 39173
rpr: 40015
dUTX: 34377"
  },
  {
    "caption": "(b) The transcript levels of Atg genes relative to the internal control gene rp49 in the salivary glands of control (blue) and dUTX1 (red) were analysed by qPCR at L3, 6 h and 14 h RPF. Data in all panels are expressed as means from three independent experiments, with error bars representing s.e.m. *P0.05 (Student's t-test).",
    "ncbi_link": "rp49: 
dUTX: 34377"
  },
  {
    "caption": "(a,b) The occupancy of dUTX on the promoter regions of apoptosis and Atg genes was detected by chromatin immunoprecipitation (ChIP). SL2 cells overexpressing HA-dUTX were chromatin-immunoprecipitated with anti-HA and anti-GFP (IgG control) antibodies following ecdysone treatment. qPCR was used to assess the binding to the promoters of dark, dronc, drice and rpr (a)",
    "ncbi_link": "GFP: 
dark: 36914
drice: 43514
dronc: 39173
rpr: 40015
dUTX: 34377"
  },
  {
    "caption": "(a,b) The occupancy of dUTX on the promoter regions of apoptosis and Atg genes was detected by chromatin immunoprecipitation (ChIP). SL2 cells overexpressing HA-dUTX were chromatin-immunoprecipitated with anti-HA and anti-GFP (IgG control) antibodies following ecdysone treatment. qPCR was used to assess the binding to the promoters of Atg1, Atg2, Atg3, Atg4, Atg5, Atg6, Atg7, Atg8a, Atg9, Atg12 and Atg18 (b), expressed relative to the internal control gene Gapdh. Results are shown as the fold enrichment of % input compared with IgG control.",
    "ncbi_link": "Gapdh: 
GFP: 
Atg1: 39454
Atg12: 39383
Atg18: 38913
Atg2: 38344
Atg3: 40044
Atg4: 33283
Atg5: 31666
Atg6: 42850
Atg7: 37141
Atg8a: 32001
Atg9: 36821
dUTX: 34377"
  },
  {
    "caption": "(c) The abundance of H3K27me3 on the promoters of apoptosis and autophagy genes detected by ChIP. SL2 cells knocked down for dUTX were chromatin-immunoprecipitated with anti-H3K27me3 and anti-GFP (IgG control) antibodies following ecdysone treatment. Results are shown as the fold enrichment of % input compared with RNAi control.",
    "ncbi_link": "GFP: 
dUTX: 34377"
  },
  {
    "caption": "(d) The occupancy of EcR on the promoter regions of dark, dronc and Atg1 by ChIP expressed relative to the internal control gene rp49. Chromatin was immunoprecipitated with anti-EcR-B1 and anti-GFP (IgG control) antibodies from SL2 cell following ecdysone treatment. Results are shown as the fold enrichment of % input compared with IgG control. Data in all panels are expressed as means from three independent experiments, with error bars representing s.e.m. *P0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
rp49: 
dark: 36914
Atg1: 39454
dronc: 39173"
  },
  {
    "caption": "(a) Levels of BR-C and E93 transcripts were measured in salivary glands isolated from third instar larvae (L3), 6 h and 14 h RPF control (blue line) and dUTX1 (red line) using qPCR and expressed relative to the internal control gene rp49.",
    "ncbi_link": "rp49: 
BR-C: 44505
E93: 44936
dUTX: 34377"
  },
  {
    "caption": "(b) The occupancy of dUTX on the promoter regions of BR-C and E93 genes detected by ChIP. SL2 cells overexpressing HA-dUTX were chromatin-immunoprecipitated with anti-HA and anti-GFP (IgG control) antibodies following ecdysone treatment. Results are shown as the fold enrichment of % input compared with IgG control. In the right hand panel abundance of H3K27me3 on the promoters of BR-C and E93 genes as detected by ChIP is shown. SL2 cells knockdown for dUTX (dUTX RNAi) were chromatin-immunoprecipitated with anti-H3K27me3 and rabbit IgG (control) antibodies following ecdysone treatment. Results are shown as the fold enrichment of % input compared with RNAi control. Data in all panels are expressed as means from three independent experiments, with error bars representing s.e.m. *P0.05 (Students t-test).",
    "ncbi_link": "GFP: 
BR-C: 44505
E93: 44936
dUTX: 34377"
  },
  {
    "caption": "(a) Mosaic clones of dUTX1 (hsFLP; ubi-GFP FRT40A/dUTX1 FRT40A) from third instar larval salivary glands with wild-type cells marked by nuclear-localized GFP (green). dUTX1 clones have high levels of H3K27me3 (red) compared with the neighbouring control cells marked by GFP. Scale bar represents 50 μm.",
    "ncbi_link": "GFP: 
ubi: 326237///38456
dUTX: 34377"
  },
  {
    "caption": "(b) Western blot analysis of the level of H3K27me3 in control and dUTX1 larval salivary glands. Alpha-tubulin and H3 serve as loading controls.",
    "ncbi_link": "dUTX: 34377"
  },
  {
    "caption": "(c) Expression of dUTX wild-type (dUTXWT) and dUTX catalytic mutant (dUTXJmj) in the salivary glands (using Sgs3-GAL4 driver) of dUTX1. Histology analysis of paraffin sections at 24 h RPF shows intact salivary glands present in dUTX1 and in dUTX1; dUTXJmj* compared with control and dUTX1; dUTXWT at 24 h RPF. Ovals indicate the position of salivary glands and fragments. Scale bar represent 50 μm. Quantification of the salivary gland phenotypic data at 24 h RPF is shown on the right.",
    "ncbi_link": "GAL4: 
Sgs3: 39288
dUTX: 34377"
  },
  {
    "caption": " Transfection of poly (I:C) induces ACE2 expression.HEK293 cells were cultured in six-well plates and transfected with poly (I:C) as indicated above using Lipofectamine 2000. HEK293 cells were then collected for RNA isolation and RT-qPCR analysis at 9 hrs post-transfection. Results in each panel are representative of three independent experiments. ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " VSV-eGFP infection induces ACE2 expression.HEK293 cells were cultured in six-well plates and infected with VSV-eGFP as indicated above. 6 hrs later, HEK293 cells were collected for RNA isolation and RT-qPCR analysis. Results in each panel are representative of three independent experiments. ",
    "ncbi_link": "eGFP: 
ACE2: 59272"
  },
  {
    "caption": " Overexpression of TBK1 or TRIF induces ACE2 expression.TBK1 is an essential activator of RNA-sensing pathway. HEK293 cells were cultured in 24-well plates. 24 hrs later, plasmids as shown above were transfected into HEK293 cells. 36 hrs after transfection, total RNA was isolation for subsequent RT-qPCR analysis. Results in each panel are representative of three independent experiments. ",
    "ncbi_link": "TBK1: 
TRIF: 
ACE2: 59272"
  },
  {
    "caption": " ACE2 expression is upregulated in the lungs from SARS-CoV MA15 infected C57Bl/6 mouse.Intranasal instillation of 102, 103 PFU of SARS-CoV MA15 in 50 µl of PBS or mock-infected with PBS alone, lungs were harvested 24 hrs later and total RNA was isolated and subjected to microarray analysis. ACE2 expression data was retrieved from Gene Expression Omnibus (GEO) microarray database (NCBI Accession: PRJNA149057; GEO: GSE33266). ",
    "ncbi_link": "ACE2: 70008"
  },
  {
    "caption": " ACE2 expression is upregulated in primary human airway epithelial cells in response to wild type MERS-CoV (icMERS-CoV EMC2012).Human airway epithelial cells were infected with a multiplicity of infection of 5 PFU per cell. Infected samples were collected as indicated above. ACE2 expression data was retrieved from GEO microarray database (NCBI Accession: PRJNA391962; GEO: GSE100504). ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " ACE2 expression is upregulated in human airway epithelial cells in response to rhinovirus infection.Primary epithelial cells from 4 donors were exposed to rhinovirus or medium only (used as control). 24 hrs post-infection, gene expression was assessed using Affymetrix U133 plus 2.0 human GeneChips. ACE2 expression data was retrieved from GEO microarray database (NCBI Accession: PRJNA137767; GEO: GSE27973). ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " ACE2 expression is upregulated in human bronchial epithelial cells (HBECs) after IFNβ and H1N1 influenza stimulation.HBECs were treated with IFNβ (1000U/ml) or wild type H1N1 influenza (A/PR/8/34). Control samples were incubated with fresh medium under the same conditions. HBECs were harvested at indicated time points (0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 18 hours post-treatment). Total RNA was extracted and analyzed using the Affymetrix High Throughput Array. ACE2 expression data was retrieved from GEO microarray database (NCBI Accession: PRJNA121751; GEO: GSE19392). ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": " ACE2 expression is upregulated in human primary keratinocytes exposed to IFNα and IFNγ.Primary keratinocytes from 3 donors were either untreated (control) or exposed to cytokines IFNα, IFNγ. 24 hrs after treatment, total RNA was extracted for subsequent microarray analysis. ACE2 expression data was retrieved from GEO microarray database (NCBI Accession: PRJNA153023; GEO: GSE36287). ",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A and B) RT-qPCR showing the enrichment of cluster C3 subpopulation (CFAP54+) in CCSC1 (A) and CCSC2 (B) spheres treated with the chemotherapeutic agent 5FU or L-OHP. Error bars represent SD of three biological replicates. P-value was calculated based on two-tailed Student's t-test. *, p<0.05; **, p<0.01; ***, p<0.001; ns, no significant.",
    "ncbi_link": "CFAP54: 144535"
  },
  {
    "caption": "(C) Representative RNA-FISH images and quantification showing the level of cluster C3 subpopulation CFAP54+ cell (red) levels in L-OHP treated xenografts. Scale bar, 40 μm. Three biological replicates were analyzed. Data represent the mean ± SD. P-value was calculated based on two-tailed Student's t test. *, p<0.05.",
    "ncbi_link": "CFAP54: 144535"
  },
  {
    "caption": "(E) Fluorescent images and quantification showing AP20187-mediated ablation of cluster C4 (PLAUR+) cells from CCSC spheres carrying PLAUR-iCaspase9-mCherry construct. Scale bar, 40 μm. Three biological replicates were analyzed. Data represent the mean ± SD. P-value was calculated based on two-tailed Student's t test. ***, p<0.001.",
    "ncbi_link": "Caspase9: 
mCherry: 
PLAUR: 5329"
  },
  {
    "caption": "(I) Representative H&E images and quantification (number of mice with invasive tumors) showing the invasive potential of cluster C4 cells (PLAUR+). CCSC sphere cells carrying PLAUR-iCaspase9-mCherry construct were orthotopically injected into the mice. AP20187 was applied to ablate cluster C4 (PLAUR+, red) cells. Red arrows indicate invasive tumor. Scale bars, left, 100 μm; right, 300 μm.",
    "ncbi_link": "Caspase9: 
mCherry: 
PLAUR: 5329"
  },
  {
    "caption": "(C) RT-qPCR analysis of the signature genes of each cluster in CCSC sphere cells with control (EV) or ATF6 knockdown (shATF6-1 and shATF6-2). Error bars represent SD of three biological replicates. P-value was calculated based on Student's t-test. *, p<0.05; **, P<0.01. Diagram without asterisk indicates no statistical difference.",
    "ncbi_link": "ATF6: 22926"
  },
  {
    "caption": "(D) RT-qPCR analysis of signature genes of each cluster in control (EV) or ATF6 knockdown (shATF6-1 and shATF6-2) under the treatment with L-OHP. Error bars represent SD of three biological replicates. P-value was calculated based on Student's t-test. ***, p<0.001. Diagram without asterisk indicates no statistical difference.",
    "ncbi_link": "ATF6: 22926"
  },
  {
    "caption": "(F) Representative RNA-FISH of cluster C3 signature gene, CFAP54 (up) and immunohistochemistry of transcription factor ATF6 (bottom) showing the influence of ATF6 knockdown (shATF6-1 and shATF6-2) on cluster C3 (CFAP54+, red) population in xenografts. The mice were treated with vehicle or L-OHP after 14 days after CCSC sphere cells were implanted. Scale bars, upper, 40 μm; lower, 80 μm.",
    "ncbi_link": "ATF6: 22926
CFAP54: 144535"
  },
  {
    "caption": "(H) RT-qPCR analysis of signature genes of each cell clusters in CCSC sphere cells with control (EV) or FOXQ1 knockdown (shFOXQ1-1 and shFOXQ1-2). Error bars denote the SD between triplicates. P-value was calculated based on Student's t test. *, p<0.05; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "FOXQ1: 94234"
  },
  {
    "caption": "(I) Representative H&E and immunofluorescence images showing the influence of FOXQ1 knockdown (shFOXQ1-1 and shFOXQ1-2) on cluster C4 (PLAUR+, red) population and tumor invasion. CCSC sphere cells carrying control (EV) vector or FOXQ1 shRNAs were orthotopically injected into mice (n=5). Scale bars, left, 300 μm; right, 100 μm. Arrows indicate the location of tumor invasion.",
    "ncbi_link": "FOXQ1: 94234"
  },
  {
    "caption": "(H and I) Representative immunohistochemistry images for ATF6 expression (H) and RNA-FISH for CFAP54 expression (I) in paired CRC tissues collected from CRC patients before chemotherapy or after chemotherapy. Scale bars, left, 200 μm; right, 40 μm. Data represent the mean ± SEM. Three to five technical replicates were analyzed. P-value was calculated based on two-tailed Student's t test. *, p<0.05; **, p<0.01; ***, p<0.001.",
    "ncbi_link": "CFAP54: 144535"
  },
  {
    "caption": " Wild type (WT) and TRIM21 knockout (KO) mice were infected with 10^5 FFU LCMV clone 13 (6 mice per group) and 2 mice were uninfected (UI). Weights were compared over 15 days post infection (pi). ",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": " Wild type (WT) and TRIM21 knockout (KO) mice were infected with 10^5 FFU LCMV clone 13 (6 mice per group) and 2 mice were uninfected (UI). Kaplan-Meier survival were compared over 15 days post infection (pi). ",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": " H) Anti-N mAb KL53 was co-electroporated with recombinant N protein into WT and KO MEFs, and immunoblotting for N was performed after 3 hours. Electroporation of recombinant KL53 expressing the TRIM21 non-binding mutation H433A was unable to mediate N protein degradation. ",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": " Wild type (WT) and TRIM21 knockout (KO) mice were infected with 0.5 x 10^5 FFU LCMV clone 13 (6 mice per group), and either received anti-N mAb KL53 (+) or control (-) intraperitoneally on days 1 and 3pi. Two mice were uninfected (UI). A) Weights were monitored throughout infection, with final day 8 weights of individual mice presented separately. ",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": " Wild type (WT) and TRIM21 knockout (KO) mice were infected with 0.5 x 10^5 FFU LCMV clone 13 (6 mice per group), and either received anti-N mAb KL53 (+) or control (-) intraperitoneally on days 1 and 3pi. Two mice were uninfected (UI). Viral titres in the spleen, liver, lung and kidney of all mice were determined by FFA day 8pi. Each data point represents one mouse, with results from two repeat experiments combined. ",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "B, C Representative Iba1 stainings of retinal flat mounts detecting microglia/macrophages in laser spots 3 days after laser coagulation in C57BL6/J controls (B) and Ifnar1-/- (C) mice. Scale bar: 20 µm.D Quantification of amoeboid-shaped mononuclear phagocytes in laser spots. Values show mean ± SD. (n = 11-12 retinas; unpaired Student's t-test: ***p = 0.0004).E Quantification of immune cell morphology in laser spots using a grid image analysis system. Values show mean ± SD. (n = 42-62 cells; unpaired Student's t-test: ***p < 0.0001).",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "F-K Representative fundus fluorescein angiography images of C57BL6/J (F-H) and Ifnar1-/- (I-K) mice 3, 7 and 14 days after laser-induced damage.L Quantification of vascular leakage by analyzing pixel intensities at 3, 7 and 14 days after laser-induced retinal damage in C57BL6/J controls versus Ifnar1-/- mice. Values show mean ± SD. (n = 14-22 eyes; One-way ANOVA followed by Tukey's post-test: ***p < 0.0001).",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "M-P Representative images of lectin stained choroidal flat mounts 7 and 14 days after laser coagulation in C57BL6/J control mice (M, N) and Ifnar1-/- animals (O, P). Dashed lines indicate CNV areas and the asterisk marks the central optic nerve head. Scale bar: 200 µm.Q Quantification of lectin-stained CNV areas with ImageJ software. Bars show mean ± SD. (n = 4-11 RPE/choroidal flat mounts; One-way ANOVA followed by Tukey's post-test: *p = 0.0281).",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "B-D Representative Iba1 staining results of retinal flat mounts detecting microglia/macrophages in laser spot 3 days after laser coagulation in Cx3cr1CreER (B), Ifnar1fl/fl (C) and Cx3cr1CreER:Ifnar1fl/fl (D) mice. Scale bar: 20 µm.E Quantification of amoeboid-shaped mononuclear phagocytes in laser spots. Values show mean ± SD. (n = 17-29 retinas; unpaired Student's t-test: ***p = 0.0003, **p = 0.0044).F Quantification of immune cell morphology in laser spots using a grid image analysis system. Values show mean ± SD. (n = 44-52 cells; unpaired Student's t-test: ***p < 0.0001).",
    "ncbi_link": "Cre: 
Cx3cr1: 
Cx3cr1: 13051
ER: 13983///13982
Ifnar1: 15975"
  },
  {
    "caption": "G-O Representative fundus fluorescein angiography images of Cx3cr1CreER (G-I), Ifnar1fl/fl (J-L) and Cx3cr1CreER:Ifnar1fl/fl (M-O) mice 3, 7 and 14 days after laser-induced damage.P Quantification of vascular leakage by analyzing pixel intensities at 3, 7 and 14 days after laser-induced retinal damage in Cx3cr1CreER, Ifnar1fl/fl and Cx3cr1CreER:Ifnar1fl/fl mice. Values show mean ± SD. (n = 5-12 eyes; One-way ANOVA followed by Tukey's post-test: **p = 0.0032, *p = 0.0247).",
    "ncbi_link": "Cre: 
Cx3cr1: 13051
ER: 13983///13982
Ifnar1: 15975"
  },
  {
    "caption": "Q-V Representative images of lectin stained choroidal flat mounts 7 and 14 days after laser coagulation in Cx3cr1CreER (Q, R), Ifnar1fl/fl (S, T) and Cx3cr1CreER:Ifnar1fl/fl (U, V) mice. Dashed lines indicate CNV areas and the asterisk marks the central optic nerve head. Scale bar: 200 µm.W Quantification of lectin-stained CNV areas with ImageJ software. Bars show mean ± SD. (n = 4-11 RPE/choroidal flat mounts; One-way ANOVA followed by Tukey's post-test: *p = 0.043, ***p = 0.0007).",
    "ncbi_link": "Cre: 
Cx3cr1: 13051
ER: 13983///13982
Ifnar1: 15975"
  },
  {
    "caption": "(B) Cross-presentation experiments to exclude release of NeoR and re‐uptake as exogenous protein. EBV‐B1.25 cells transfected with the neoR expression plasmid pINCO‐NeoR, were co‐cultured for 24 h with the same number of untransfected EBV‐B1.11 cells, or vice versa. Then, T cells were added and co‐cultured with the cells for additional 24 h. To test for NeoR release by neoR‐transfected EBV‐B1.11 cells, total supernatant (200 μl) of 1×105 EBV‐B1.11 cells was harvested 48 h post transfection by centrifugation, and was used as culture media for 1×105 untransfected EBV‐B1.11 cells. After 48 h, 1×105 20-4/A4 T cells were added and GM‐CSF concentration determined after additional 24 h.",
    "ncbi_link": "neoR: 
NeoR: 
pINCO: "
  },
  {
    "caption": "(A), pINCO‐NeoR transfected EBV‐B1.11 cells (B), and as control pINCO‐Tyrosinase‐transfected EBV‐B1.11 cells (C), were either left untreated or treated with 5 μM lactacystin or 50 μM AAF‐CMK for 20 h. Following fixation with 0.5% paraformaldehyde, cells were incubated with T cells, and 24 h later GM‐CSF release was determined by ELISA.",
    "ncbi_link": "NeoR: 
pINCO: 
Tyrosinase: 7299"
  },
  {
    "caption": "(D) FACS analysis of EBV‐B1.11 cells (open histograms) and EBV‐B1.11 cells stably transfected with the ICP47 gene (shaded histograms). Inhibition of TAP by ICP47 down‐regulates HLA class I but not HLA‐DP expression. An isotype‐matched antibody was used as control (thin‐lined histogram). EBV‐B1.11‐ICP47 cells were transfected with pINCO‐NeoR (E), pINCO‐Tyrosinase (F), or mock transfected (pINCO) and MHC‐restricted presentation monitored with T cells.",
    "ncbi_link": "NeoR: 
pINCO: 
Tyrosinase: 7299
ICP47: 1487353"
  },
  {
    "caption": "(A) RCC1.24‐NeoR incubated with IFN‐γ were either left untreated (w/o) or treated with chloroquine or leupeptin for 24 h to block lysosomal processing. Subsequently cells were fixed with 0.5% paraformaldehyde and tested with 20-4/A4 in a GM‐CSF release assay. EBV‐B1.11 cells transfected with pINCO‐NeoR (B) or pINCO‐Tyrosinase (C) were tested likewise. Both substances abrogated recognition of neoR‐transfected cells, while HLA‐A2‐restricted presentation of the tyrosinase peptide was not affected",
    "ncbi_link": "NeoR: 
neoR: 
pINCO: 
Tyrosinase: 7299"
  },
  {
    "caption": "(A) 293T cells transfected with pINCO‐NeoR were harvested 6 and 96 h post transfection and NeoR localization within various cell fractions determined by Western blot. In addition, supernatant of NeoR‐pINCO transfected 293T cells (96 h post transfection) was included to test for release of NeoR into the culture supernatant. At 6 h post transfection, NeoR protein becomes detectable in the cytoplasm, while at 96 h post transfection a substantial amount of NeoR protein is also localized in the endosomal/lysosomal fraction. For further characterization of the various fractions, blots were stripped and re‐probed with antibodies specific for the cytoplasmic protein LDH, the nuclear protein c‐myc, early endosomes (Rab‐5), late endosomes and lysosomes (Lamp‐1) and mitochondria (cytochrome c), which co‐purify with endosomes/lysosomes.",
    "ncbi_link": "pINCO: "
  },
  {
    "caption": "(B) Endosomal/lysosomal fractions were prepared from pINCO‐NeoR‐transfected cells 96 h post transfection as in (A). To prevent lysosomal degradation of NeoR, half of the cells were treated with leupeptin for the last 48 h. These fractions were separated on a 27% Percoll gradient and eight different fractions collected. Successful separation into fractions with increasing density was verified by Western blot analysis with antibodies directed against Lamp‐1, Rab‐5 and cytochrome c. Inhibition of NeoR degradation by leupeptin causes accumulation of NeoR protein in the late endosomal/lysosomal fractions 7 and 8.",
    "ncbi_link": "pINCO: "
  },
  {
    "caption": "(C) To determine where NeoR gains access to the vacuolar system, 293T cells were transfected with pINCO‐NeoR, treated with leupeptin to prevent NeoR degradation, and the endosomal/lysosomal fractions prepared at various time points post transfection and separated by Percoll gradient centrifugation. Starting at 16 h post transfection, NeoR becomes detectable in the Rab‐5‐positive fraction 5, and then spreads into late endosomal/lysosomal fractions. At 26 h post transfection an almost identical NeoR distribution pattern is observed in cells treated with or without BfA.",
    "ncbi_link": "pINCO: "
  },
  {
    "caption": "(C) Western blot analysis of neoR‐transfected cells. Treatment of cells with 7.5 mM 3‐MA causes a dramatic increase in NeoR protein levels in only 12 h. The ER‐resident protein BiP was used as gel loading control.",
    "ncbi_link": "neoR: "
  },
  {
    "caption": "(E) Western blot analysis of whole cell lysates prepared from neoR‐transfected cells. Inhibition of protein synthesis by cycloheximide treatment leads to a rapid decrease in NeoR protein levels. Simultaneous treatment of cells with 3‐MA prevents NeoR degradation. BiP was again used as a gel loading control.",
    "ncbi_link": "neoR: Q76MW8"
  },
  {
    "caption": "(B) EBV‐B1.11 cells transfected with pINCO‐NeoR (endogenous), or incubated with recombinant NeoR protein (exogenous), were treated with the inhibitors of autophagy, wortmannin and 3‐MA, and HLA‐DP3‐restricted presentation of the NeoR‐derived peptide determined. Inhibition of antigen presentation by leupeptin served as control.",
    "ncbi_link": "pINCO: "
  },
  {
    "caption": "(C) Presentation of the HLA‐A2‐restricted tyrosinase peptide in EBV‐B1.11 cells transfected with pINCO‐Tyrosinase is not affected by these inhibitors of autophagy.",
    "ncbi_link": "pINCO: 
Tyrosinase: 7299"
  },
  {
    "caption": "G Luminescence derived from HEK293T transfected with GA-NLuc reporters WT or mutated and treated for 24 h. Mutational analysis of near-cognate CUG start codon from three biological replicates and four technical replicates, n = 12. Data are mean ± SEM. 2-way ANOVA followed by Dunnett's multiple comparisons test, ****P<0.0001. Concentration used: 1 μM GELD, 10 μM SPL and FSK.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "C Relative  expression level of Sqstm1/p62, Lc3, Tfeb, Hspb8 and  Bag3  mRNAs in  NSC34 cells treated for 24 h. Data are mean ± SEM from three biological replicates. 2-way ANOVA followed by Dunnett's multiple comparisons test, ***P<0.001. Dotted lines represent RNA expression in the DMSO control. Concentration used: 1 μM  GELD, 10 μM ERY, SPL, FSK.",
    "ncbi_link": "Bag3: 29810
Hspb8: 80888
Lc3: 66734
p62: 18412
Sqstm1: 18412
Tfeb: 21425"
  },
  {
    "caption": "F  Luminescence derived from HEK293T transfected with GA-NLuc reporters WT or mutated and treated with H89 for 24 h. Mutational analysis of near-cognate CUG start codon from three biological replicates and four technical replicates, n = 12. Data are mean ± SEM. 2-way ANOVA followed by Dunnett's multiple comparisons test, *P = 0.0130 WT  H89  vs WT DMSO, ****P<0.0001, CUG mutated  H89 vs CUG mutated  DMSO. Concentration used: 2.5 μM H89, ",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "A, B Lysates from HEK293T cells, transfected with RNAi scrambled or RNAi PRKACA (72 h) and 2R or 66R (24 h), immunoblotted  for  PKA-Cα and poly-GA (HA-tag) expression.  α-Tubulin used as loading control. (B) Quantification of  PKA-Cα and poly-GA expression from three biological replicates. Data are mean ± SEM. Two-tailed, unpaired t-test.  PKA-Cα: ns siScr 66R vs siScr 2R, ***P = 0.0002 siPRKACA  66R vs siScr 2R, ***P = 0.0003 siPRKACA 66R vs siScr 66R. poly-GA expression: ****P<0.0001 siScr 66R vs siScr 2R, ****P<0.0001 siPRKACA 66R vs siScr 2R, **P = 0.0062 siPRKACA 66R vs siScr 66R . C, D Lysates from HEK293T  cells, transfected with RNAi scrambled or RNAi PRKACB (72 h) and 2R or 66R (24 h), immunoblotted PKA-Cβ and poly-GA (HA tag) expression. α-Tubulin used as loading control. (D) Quantification of PKA-Cβ  and poly-GA expression from three biological replicates. Data are mean ± SEM. Two-tailed, unpaired t-test. PKA-Cβ: ns siScr 66R vs siScr 2R, **P = 0.0049 siPRKACB 66R vs siScr 2R, **P = 0.0091 siPRKACB  66R vs siScr 66R. poly-GA expression: ****P<0.0001 siScr 66R vs siScr 2R, ****P<0.0001 siPRKACB 66R vs siScr 2R, ***P = 0.0007 siPRKACB 66R vs siScr 66R. E ",
    "ncbi_link": "PRKACA: 5566
PRKACB: 5567"
  },
  {
    "caption": "A, B Representative graphs showing the climbing ability  flies carrying the UAS-(G4C2)x36 construct in  neurons using the  Elav-gal4 promoter upon treatment with H89  10 µM diluted with 0.1 % of DMSO and 5% sucrose in PBS. The wild-type (w1118) line was used as control. (A) Female flies (♀). Data are mean ± SD. 2-way ANOVA followed by Tukey's multiple comparisons, significance is reported for the 6th day of treatment ****P<0.0001 (G4C2)x36 vs (G4C2)x36 + H89. (B) Male flies (♂). Data are mean ± SD. 2-way ANOVA followed by Tukey's multiple comparisons, significance is reported for the 6th day of treatment. ****P<0.0001 (G4C2)x36 vs (G4C2)x36 + H89. Experiments were performed three times, N=15 adult flies were used for each genotype, sex and treatment (N tot=45). C, D Representative graphs showing climbing activity of flies co-expressing the UAS-Pka-RNAi construct (1, v330111) in combination with UAS-(G4C2)x36 in neurons using the Elav-gal4 promoter. The wild-type (w1118) line was used as control. (C) Female flies (♀). Data are mean ± SD. 2-way ANOVA followed by Tukey's multiple comparisons, significance is reported for the 9th day ****P<0.0001 (G4C2)x36 vs Pka-RNAi (1);(G4C2)x36. (D) Male flies (♂). Data are mean ± SD. 2-way ANOVA followed by Tukey's multiple comparisons, significance is reported for the 7th day ****P<0.0001 (G4C2)x36 vs Pka-RNAi (1);(G4C2)x36. Experiments were performed twice with different RNA interfering sequence, N=15 adult flies were used for each genotype and sex (N tot=30). ",
    "ncbi_link": "gal4: 
Elav: 31000
Pka: 34284///43644///39733
Pka: 39733///43644///34284"
  },
  {
    "caption": "F Relative fold changes of C9orf72  variant RNA levels normalised to RPL13A, after 14-day 10 µM H89 treatment vs vehicle treatment (N=1 C9 patient  line, four technical replicates). No significant changes were observed between  H89 and vehicle for any of the isoforms (2-way ANOVA with Šídák's multiple comparisons test, all not significant, P>0.05). Data information: Error bars reported as ± SD. Not significant = P>0.05, *P<0.05, **P<0.01. T ",
    "ncbi_link": "C9orf72: 203228
RPL13A: 23521"
  },
  {
    "caption": "(A) Alcian blue‐stained sections of descending colons from control and Atg5VC mice. The area between the two black dashed lines indicates the crypt base where epithelial progenitors and nascent goblet cells reside. Bars=200 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(B) Quantification of average mucin area/goblet cell in control and Atg5VC mice (n=5-7 mice/group from 3 independent experiments; 100 goblet cells measured/mouse). **P0.01 as determined by the Student's t‐test. This analysis was performed on upper crypt goblet cells (above the upper dashed line in A).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(D) TEM images of upper crypt goblet cells from control and Atg5VC transverse colons. The yellow dashed lines outline the mucin granules in the apex of the cells. Bars=2 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(G, H) Whole‐mount images of the mucosal surface from control and Atg5VC transverse colons. Whole‐mount colonic samples were either stained with Ulex europaeus agglutinin‐1 (UEA) that labelled mucus (G) or analysed by the scanning electron microscopy (H). Yellow arrows indicate the crypt opening orifices. Green arrowheads indicate goblet cells protruding from the surface epithelium of Atg5VC mice (insets in H show higher power image of the latter). Bars=100 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(C, D) Graph of relative expression (as measured by qRT‐PCR) of Atoh1 (C) and Muc2 (D) mRNAs comparing spheroids grown in either 5% CM or 5% CM+ DAPT to spheroids grown in 50% CM (n=4-5 samples/group). Error bars indicate s.e.m. *P0.05; **P0.01 as determined by a two‐tailed Student's t‐test.",
    "ncbi_link": "Atoh1: 11921
Muc2: 17831"
  },
  {
    "caption": "(E, F) Images of colonic epithelial spheroids isolated from control and Atg5VC mice grown in 5% CM+DAPT and stained for Muc2 (green: E) or with the lectin, UEA (red: F). Bars=20 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(H) Relative expression of Muc2 mRNA in differentiated spheroids from control and Atg5VC mice as measured by qRT-PCR (n=4-5 samples/group). No statistically significant differences were found in Muc2 expression as determined by the Student's t‐test.",
    "ncbi_link": "Atg5: 11793
Muc2: 17831"
  },
  {
    "caption": "(I, K) Images of FIP200f/f (I) and Atg14f/f (K) colonic epithelial spheroids treated with recombinant Tat‐Cre and stained with UEA (red).",
    "ncbi_link": "Atg14: 100504663
FIP200: 12421"
  },
  {
    "caption": "(A) Images of colonic sections stained for LC3β (green) from control and Atg5VC mice. The white‐dashed lines indicate the border between the basal surface of the crypt epitheliumand the mesenchyme. White asterisks denote non‐specific plasma cell staining from the mouse monoclonal anti‐LC3β antibody. Bars=50 μm.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(C) Enriched KEGG pathways for Atg5‐deficient epithelial cells obtained from a microarray comparing control and Atg5VC colonic crypt base epithelium. P‐values were determined by modified Fisher's exact test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A) Colonic epithelial monolayers from a wild‐type and p22 mut mouse stained with LC3β (green) and EEA1 (red). Bar=5 μm.",
    "ncbi_link": "p22: 13057"
  },
  {
    "caption": "(D) LC3 immunoblots of either wild‐type or p22 mut epithelial spheroids treated with 100 nM BafA1 as indicated. Representative image is shown from n=3 experiments.",
    "ncbi_link": "p22: 13057"
  },
  {
    "caption": "(G) Colonic epithelial cellspheroids from control and p22 mut mice stained with TRITC‐UEA to label goblet cellmucin. Bars=50 μm.",
    "ncbi_link": "p22: 13057"
  },
  {
    "caption": "(A) Colonic epithelial cell spheroids from p22phox−/−, Atg5VC and wild‐type mice. Wild‐type spheroids were treated with vehicle (control), 10 μM DPI (NADPH oxidase inhibitor) or 100 μM Dynasore. Intracellular ROS in live cells were labelled by 5 μM DCF. Bars=100 μm.",
    "ncbi_link": "Atg5: 11793
p22phox: 13057"
  },
  {
    "caption": "(B) Images of control and Atg5VC colonic epithelial spheroids labelled with TRITC‐UEA (red) after treatment with either vehicle or 300 μM H2O2. Bars=20 μm. (C) Quantification of average mucin area/goblet cell (n=6 samples/group; 150 cells were quantified/sample). ***P0.001, ****P.0001 as determined by ANOVA with Tukey's multiple post‐test comparisons.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(D) Relative expression of Muc2 mRNA in differentiated spheroids from control and Atg5VC mice treated with either vehicle or 300 μM H2O2 as measured by qRT-PCR. No statistically significant differences were found in either group as determined by ANOVA.",
    "ncbi_link": "Atg5: 11793
Muc2: 17831"
  },
  {
    "caption": "(E, G) Images of p22 mut or Dynasore‐treated colonic epithelial spheroids (mucin is labelled with TRITC‐UEA; red) after treatment with either vehicle or 300 μM H2O2. Bars=20 μm. (F, H) Quantification of average mucin area/goblet cell (n=6 sample/group; 30-60 cells were quantified/sample) corresponding to experiments performed using p22 mut (E) and Dynasore‐treated wild‐type spheroids (G)",
    "ncbi_link": "p22: 13057"
  },
  {
    "caption": "Atg5VC and p22 mut spheroids were treated with 300 μM H2O2 plus or minus 100 μM BAPTA‐AM (I) or PMA/ionomycin (J). (I, J) Quantification of average mucin area/goblet cell (n=5 sample/group; 150 cells were quantified/sample). Error bars indicate s.e.m. ****P0.0001 as determined by the Student's t‐test (I) or ANOVA with Tukey's multiple post‐test comparisons (J).",
    "ncbi_link": "Atg5: 11793
p22: 13057"
  },
  {
    "caption": "a) Auto-ubiquitination assays in which the E3 acts as both an E3 and as proxy substrate were performed with GST-HHARIRBR, T7-Triad1ΔAri, GST-ParkinRBR, and Flag-BRCA1/BARD1 and either UbcH5WT or UbcH5L104Q as the E2. Products were visualized by western blotting against indicated tags on E3s. Times given are post-ATP addition.",
    "ncbi_link": "UbcH5: 7323///7322///7321"
  },
  {
    "caption": "b) Overlay of (1H,15N)-HSQC-TROSY spectra of 15N-UbcH5-O-15N-Ub in the absence (black) and presence (red) of 0.5mol equiv. HHARI RING1. A subset of UbcH5 peaks, but not Ub peaks, shift and broaden upon HHARI RING1 binding.",
    "ncbi_link": "HHARI: 25820"
  },
  {
    "caption": "b) Region of 1H-15N-HSQC TROSY spectra containing resonances of the cross-over helix residues S107 and Q106 are overlaid: unconjugated 15N-UbcH7 (blue), 15N-UbcH7-O-Ub (black), and 15N-UbcH7-O-UbI44A (red). Peaks representing S107 and Q106 in the context of UbcH7~Ub-I44A (red) are closer to peaks observed in free UbcH7 (blue) than UbcH7~Ub-WT (black) indicating that I44A of Ub disrupts interactions with the cross-over helix of UbcH7.",
    "ncbi_link": "Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "c) Regions of 1H-15N-HSQC-TROSY spectra of UbcH7-O-15N-Ub in the absence (black) and presence (red) of a RING1 domain from the RBR E3s HHARI (left) or RNF144 (middle) or a canonical RING domain of BRCA1/BARD1 (right). The perturbations on Ub due to binding of HHARI RING1 and RNF144 RING1 are remarkably similar, while binding of the canonical RING domain of BRCA1/BARD1 has no observable effect on the Ub spectrum. Gray boxes mark area expanded in a)",
    "ncbi_link": "HHARI: 25820
BARD1: 580
BRCA1: 672
RNF144: 255488///9781"
  },
  {
    "caption": "b) LEFT. Auto-ubiquitination assays were performed with wild-type HHARIRBR or an active site-dead mutant (C357A- HHARIRBR). Products were visualized by western blotting against GST. The zero time point was taken immediately prior to ATP addition, all other times are post-ATP addition. RIGHT. Identical assays as shown on left were performed with the UBR-hybrid. The active site-dead mutant (C357A) retains substantial auto-ubiquitination activity signifying that UbcH5~Ub is able to transfer Ub directly onto the GST-UBR-hybrid construct, bypassing the RING2 active site Cys.",
    "ncbi_link": "HHARI: 25820"
  },
  {
    "caption": "a) LEFT. E3 auto-ubiquitination assays were performed using various Ub mutants (I44A, R42A, Q49A, Q49E, and V70A) and the RBR E3s HHARIRBR (left) and ParkinRBR (right). Products were visualized by western blotting against HA-Ub. Samples were analyzed 30 minutes after ATP addition.",
    "ncbi_link": "Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "c) UbcH7~Ub conjugates were preformed with either with WT-Ub or I44A-Ub. After the addition of apyrase to quench the charging reaction, UbcH7~UbWT (left) or UbcH7~UbI44A (right) was incubated with ParkinRBR. The disappearance of each UbcH7~Ub species and appearance of auto-ubiquitinated E3 was visualized under non-reducing conditions by western blotting for HA-Ub. Time was recorded post addition of ParkinRBR. E2~Ub conjugated with I44A-Ub does not disappear over the time course of the reaction.",
    "ncbi_link": "Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "d) UbcH7 conjugated with WT-Ub, I44A-Ub, or V70A Ub as indicated was incubated with either H887A-HOIPRBR-LDD (left) or H359A-HHARIRBR (right) mutants that allow trapping of the E3~Ub thioester with WT-Ub (Stieglitz et al, 2013;[29]). While a HOIP~Ub thioester species is observed when UbcH7 was charged with WT-Ub, no detectable transfer occurs with the I44A-Ub conjugate (left). Similarly, V70A-Ub shows reduced formation of the HHARI~Ub thioester (right). In addition to blotting for HA-Ub, the blot on the right was also blotted for GST-HHARI.",
    "ncbi_link": "Ub: 7311///6233///7314///7316"
  },
  {
    "caption": "a) Top panel. Regions of 1H-15N-HSQC TROSY spectra of 15N-HHARI RING2 in the absence (black) and presence of excess Ub (red). Middle panel. Identical spectral region, but in the presence of Ub-V70A (red). Bottom panel. Identical spectral region, but spectra are from a truncated HHARI RING2 construct that lacks N-terminal residues 325-335 (HHARI RING2-ΔL).",
    "ncbi_link": "HHARI: 25820
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "d) Mutations in the Ub binding surface of RING2 decrease activity in E3 auto-ubiquitination assays. Time points (10min) are visualized by western blotting for the GST-tag on HHARI. Relative activity of HHARI WT and mutant forms is clearest when the intensity of the unmodified HHARI band is compared.",
    "ncbi_link": "HHARI: 25820"
  },
  {
    "caption": "e) 1H-15N-HSQC TROSY spectra of 15N-Ub demonstrate binding by WT HHARI RING2, but not by mutant HHARI RING2 constructs that exhibit decreased auto-ubiquitination activity. Overlay of 15N-Ub spectra in the absence (black) and presence of WT-HHARI RING2 (red), W336A-HHARI RING2 (blue), T341N-HHARI RING2 (green), or E352A-HHARI RING2 (purple). HHARI mutations that exhibited reduced binding to Ub also show decreased ubiquitination activity in panel d).",
    "ncbi_link": "HHARI: 25820"
  },
  {
    "caption": "(B) Representative images of immunostaining demonstrate that FKRP-iPSCs express specific pluripotency-associated markers, including NANOG, OCT4, Tra-1-60 and SSEA4. Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(C) FKRP-iPSCs have a normal karyotype. Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(D) In vitro differentiation of FKRP-iPSCs to cells representing ectoderm (β-III Tubulin, Tuj1), mesoderm (SMA, smooth muscle actin) and endoderm (AFP, α-fetoprotein). Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(C) Sequence analysis shows precise biallelic correction of the FKRP mutation in three independently corrected iPSC clones (5D17, 5D23 and 3B17), compared with their parental FKRPA455D-iPSCs. Selection cassette excision sites are identified in the corrected-iPSC lines.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(D) CRISPR/Cas9 corrected-iPSC lines show a normal karyotype.",
    "ncbi_link": "CRISPR: 
Cas9: 901176"
  },
  {
    "caption": "(A and B) Representative images of NSCs derived from FKRP- and corrected-iPSC lines expressing SOX1, SOX2 and nestin. (C and D) Quantification of percentage of SOX1+ (C) and SOX2+ (D) cells in culture. The efficiency of neural induction is more than 99% in FKRP- and corrected-iPSC (5D17, 5D23 and 3B17) lines. Data are mean ± s.d. n = 4 technical replicates. Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(E and F) FKRP- and corrected NSC lines can be further differentiated to cortical neural progenitor cells, expressing PAX6, OTX2 and vimentin. (G-I) Quantification of percentage of PAX6+ (G) and OTX2+ (H) cells in culture. About 91-98% of cells derived from FKRP, 5D17, 5D23 and 3B17 NSC lines express PAX6 (G). About 93-96% of cells derived from FKRP, 5D17, 5D23 and 3B17 NSC lines express OTX2 (H). Of the OTX2+ population, about 60-67% cells are also Ki67+ cycling progenitors (I). Data are mean ± s.d. n = 4 technical replicates. Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(J and K) Glutamatergic projection neurons derived from FKRP and corrected (5D17, 5D23 and 3B17) progenitor cells. The vast majority of neurons contain vGlut1+ punctae in their neurites (labelled by Tuj1). Right panels are enlarged images from the insets of left panels. Data information: Scale bars, 50 μm.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(A) Molecular weight of glycosylated α-dystroglycan (IIH6 epitope) in WT-iPSC derived cortical neurons is similar to that in the mouse brain (~120 kDa) and lower than that in the mouse muscle (~156kDa). IIH6 reactivity was almost not detected in cortical neurons derived from FKRP-iPSCs. Note that the β-Actin antibody does not cross-react with the muscle sample.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(B) Representative immunoblots show that targeted gene correction of FKRP restores IIH6 reactivity in iPSC-derived cortical neurons. Intensities of IIH6 reactivity are normalized to β-Actin expression, indicating mean ± s.d. (n = 3 biological replicates; t-test; ** p<0.01)",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(A) FKRP-NSCs treated with 4BPPNit showed increased IIH6 reactivity, compared with untreated control cells. Note that the augmented IIH6 reactivity by 4BPPNit is much weaker than the that in CRISPR-corrected NSCs. Under the same exposure time, the signal intensity of IIH6 reactivity is saturated in corrected-NSCs. Data information: Intensities of glycosylation are normalized to GAPDH protein expression.",
    "ncbi_link": "CRISPR: 
FKRP: 79147"
  },
  {
    "caption": "(B) Representative immunoblots with the IIH6 antibody using FKRP- and corrected-NSCs treated with 4BPPNit for 24, 48 and 72 h, and DMSO only controls. Data information: Intensities of glycosylation are normalized to GAPDH protein expression. Note that the left and right panels of the immunoblots are not equivalent exposure time.",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(D) Representative immunoblots of laminin-binding analysis using FKRP- and corrected-NSCs treated with 4BPPNit and DMSO only controls. (E) Quantification of laminin-binding activities, compared with DMSO only controls. Data information: Intensities of laminin-binding activity are normalized to GAPDH protein expression. Note that the left and right panels of the immunoblots are not equivalent exposure time. Values indicate mean ± s.d. (n= 3 or 4 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01).",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(F) Representative immunoblots with the AF6868 antibody detecting both α-dystroglycan core protein and β-dystroglycan in FKRP- and corrected-NSCs treated with 4BPPNit and DMSO only controls. (G) Quantification of α-dystroglycan core protein and β-dystroglycan expression, compared with DMSO only controls.Data information: Intensities of protein expression are normalized to GAPDH protein expression. Values indicate mean ± s.d. (n= 3 or 4 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01).",
    "ncbi_link": "FKRP: 79147"
  },
  {
    "caption": "(A) DAG1 gene expression analysis in FKRP- and corrected-NSCs treated with 4BPPNit, compared with DMSO only controls. Data information: Gene expression levels are normalized to ACTB gene expression. Values indicate mean ± s.e.m. (n= 6 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01",
    "ncbi_link": "ACTB: 60
DAG1: 1605
FKRP: 79147"
  },
  {
    "caption": "(B) FKRP gene expression analysis in FKRP- and corrected-NSCs treated with 4BPPNit, compared with DMSO only controls. Data information: Gene expression levels are normalized to ACTB gene expression. Values indicate mean ± s.e.m. (n= 6 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01).",
    "ncbi_link": "ACTB: 60
FKRP: 79147"
  },
  {
    "caption": "(C) LARGE1 gene expression analysis in FKRP- and corrected-NSCs treated with 4BPPNit, compared with DMSO only controls. Data information: Gene expression levels are normalized to ACTB gene expression. Values indicate mean ± s.e.m. (n= 6 biological replicates; One-way ANOVA; NS, not significant; * p<0.05; ** p<0.01). ",
    "ncbi_link": "ACTB: 60
FKRP: 79147
LARGE1: 9215"
  },
  {
    "caption": "(A) The bar graph represents top 10 biological pathways upregulated in gene ontology (GO) based Reactome pathway analysis using a set of genes induced (1.5 fold, p<0.05 (Wald Test), 3 biological replicates) in RNA-seq analysis in IRGM shRNA knockdown HT29 cells compared to control shRNA cells. Heatmaps were generated for sentinel interferon-regulated genes (three biological replicates) using 'ComplexHeatmap' library using 'R' Bioconductor package where the gene expression matrix was transformed into z-score. The heat map was generated from the common genes present in the three GO terms indicated by the three black lines. The numbers on the bars indicate the p-value of that particular GO term.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(D) The qRT-PCR validation of RNA- seq data in control and IRGM KD HT29 cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(E) The bar graph represents the top pathways upregulated in GO-based Reactome pathway analysis using set of genes induced (1.5 fold, p<0.05 (Wald Test), 3 mice each group) in the brain of Irgm1-/- mice compared to Irgm1+/+ wild type mice. Heatmaps were generated for sentinel interferon-regulated genes (three biological replicates) using 'ComplexHeatmap' library using 'R' Bioconductor package where the gene expression matrix was transformed into z-score. The heat map was generated from the common genes present in the three GO terms indicated by the three black lines. The numbers on the bars indicate the p-value of that particular GO term.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(H) The qRT-PCR validation of RNA- seq data in Irgm1+/+ and Irgm1-/- mouse brain.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(A) Heat map of nucleic acid sensor proteins upregulated in IRGM KD HT29 cells and Irgm1-/- mouse brain and BMDMs.",
    "ncbi_link": "IRGM: 345611
Irgm1: 15944"
  },
  {
    "caption": "Western blot analysis to determine levels of nucleic acid sensor proteins with lysates of (B) HT29 control (henceforth IRGM+/+) and single allele CRISPR knockout IRGM cells (henceforth IRGM+/-),",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis to determine levels of nucleic acid sensor proteins with lysates of (C) HT29 cells stably expressing control shRNA or IRGM shRNA,",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis to determine levels of nucleic acid sensor proteins with lysates of (D) Irgm1+/+ and Irgm1-/- mouse brain (n=3 mice).",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(E) Western blot analysis to determine levels of adaptor proteins in control and IRGM+/- HT29 cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(F) SDD-AGE followed by western blot analysis with a mitochondrial fraction from control and IRGM siRNA knockdown THP1 cells. Western blot analysis with cytoplasmic fraction was also performed.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis performed with lysates of (G) control and stable IRGM shRNA knockdown HT29 cells (H) IRGM+/+ and IRGM+/- HT29 cells",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis performed with lysates of (I) Irgm1+/+ and Irgm1-/- mouse brain to determine levels of TBK1 protein.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "Western blot analysis performed with lysates of (J) IRGM+/+ and IRGM+/- HT29 cells",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis performed with lysates of (K-L) Irgm1+/+ and Irgm1-/- mouse brain to determine levels of IRF proteins.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "Western blot analysis performed with lysates of (M) IRGM+/+ and IRGM+/- HT29 cells",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis performed with lysates of (N) Irgm1+/+ and Irgm1-/- mouse brain to determine levels of STAT proteins (n=3 mice).",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "Western blot analysis performed with lysates of (O) IRGM+/+ and IRGM+/- HT29 cells. 2 biological replicates are shown.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "Western blot analysis performed with lysates of (P) Irgm1+/+ and Irgm1-/- mouse brain to determine levels of ISG proteins (n=2 mice).",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(Q) Representative confocal image of immunofluorescence assay performed with IRGM+/+ and IRGM+/- HT29 cells stained with MX1 antibodies. Scale bar, 10 µm.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(F) Western blot analysis with the lysates of HT-29 cells stably transfected with control or Flag-IRGM plasmid and probed with the indicated antibodies.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "(J-K) The qRT-PCR analysis with RNA isolated from (J) control and Flag-IRGM stable HT-29 cells (K) THP-1 cells transiently transfected with control or Flag-IRGM plasmid.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "(O) Western blotting analysis with lysates of control and untreated or Bafilomycin A1 (300 nM; 4 h and 8 h) treated Flag-IRGM expressing HT29 stable cell lines.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "(P) Western blotting analysis with lysates of control and untreated or chloroquine (50 µM; 4 h and 8 h) treated Flag-IRGM expressing HT29 stable cell lines.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "(Q) The qRT-PCR analysis with RNA isolated from untreated or Bafilomycin A1 (300 nM; 4 h, 8 h, and 12 h) treated control or Flag-IRGM expressing HT-29 stable cells as indicated.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "(A) The cell lysates of control or BECLIN1 siRNA transfected THP-1 cells expressing GFP or GFP-IRGM were subjected to immunoblotting with indicated antibodies.",
    "ncbi_link": "GFP: 
BECLIN1: 8678
IRGM: 345611"
  },
  {
    "caption": "(B) The cell lysates of control or ATG5 siRNA transfected THP-1 cells expressing GFP or GFP-IRGM were subjected to immunoblotting with indicated antibodies.",
    "ncbi_link": "GFP: 
ATG5: 9474
IRGM: 345611"
  },
  {
    "caption": "(C-D) qRT-PCR analysis with RNA isolated from control or BECLIN1 siRNA transfected THP-1 cells expressing 3X-Flag epitope or Flag-IRGM as indicated.",
    "ncbi_link": "Flag: 
BECLIN1: 8678
IRGM: 345611"
  },
  {
    "caption": "qRT-PCR analysis with RNA isolated from control or ATG5 siRNA transfected THP-1 cells expressing 3X-Flag epitope or Flag-IRGM as indicated.",
    "ncbi_link": "Flag: 
ATG5: 9474
IRGM: 345611"
  },
  {
    "caption": "qRT-PCR analysis with RNA isolated from control or ATG5 siRNA transfected THP-1 cells expressing 3X-Flag epitope or Flag-IRGM as indicated.",
    "ncbi_link": "Flag: 
ATG5: 9474
IRGM: 345611"
  },
  {
    "caption": "(G-H) qRT-PCR analysis with RNA isolated from control or p62 siRNA or BECLIN1 siRNA transfected HT29 cells expressing 3X-Flag epitope or Flag-IRGM as indicated.",
    "ncbi_link": "Flag: 
BECLIN1: 8678
IRGM: 345611
p62: 8878"
  },
  {
    "caption": "(K-M) Co-IP analysis of the interaction between GFP IRGM with (K) Flag-cGAS, (L) Flag-RIG-I, (M) Flag-TLR3 in control siRNA or p62 siRNA transfected HEK293T cell lysates.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(N) The cell lysates of control or p62 siRNA transfected THP-1 cells expressing GFP or GFP- IRGM (as indicate) were subjected to immunoblotting with indicated antibodies.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(O) The qRT-PCR analysis with RNA isolated from control or p62 transfected THP-1 cells expressing 3X-Flag epitope or Flag-IRGM as indicated.",
    "ncbi_link": "Flag: 
IRGM: 345611
p62: 8878"
  },
  {
    "caption": "(P-R) Co-IP analysis of the interaction between HA-p62 and (P) Flag-RIG-I, (Q) Flag-TLR3, (R) Flag-cGAS in the absence and presence of GFP or GFP-IRGM in HEK293T cell lysates.",
    "ncbi_link": "GFP: 
IRGM: 345611"
  },
  {
    "caption": "(A) Representative confocal images of Irgm1+/+ and Irgm1-/- mouse BMDMs processed for IF analysis with Tom20 antibody. Scale bar, 5 µm. Zoom panels are digital magnifications.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(B) The graph depicts the percentage of cells with swollen/rounded mitochondria in Irgm1+/+ and Irgm1-/- mouse BMDMs.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(C) Representative confocal (STED) images of Irgm1+/+ and Irgm1-/- mouse BMDMs processed for IF analysis with Tom20 and Parkin antibodies. Line profile: Co-localization analysis using line intensity profiles.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(D) Representative confocal (STED) images of Irgm1+/+ and Irgm1-/- mouse BMDMs processed for IF analysis with Tom20 and Pink1 antibodies. Line profile: Co-localization analysis using line intensity profiles.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(E) Representative confocal images of control siRNA and IRGM siRNA transfected THP-1 cells processed for IF analysis with Ubiquitin (green) and TOM20 (red) antibodies. Scale bar, 10 µm.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(F) Western blot analysis of mitochondrial fraction of control siRNA and IRGM siRNA transfected THP-1 cells, probed with indicated antibodies.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(G) Western blot analysis of mitochondrial fraction of Irgm1+/+ and Irgm1-/- mouse BMDM cells, probed with indicated antibodies (n=2 mice).",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(H) Western blot analysis of mitochondrial fraction of Irgm1+/+ and Irgm1-/- mouse BMDM cells untreated or treated with Bafilomycin A1 (300 nM, 3 h), probed with indicated antibodies.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(I) Western blot analysis of mitochondrial fraction of control siRNA and IRGM siRNA transfected THP-1 cells untreated or treated with Bafilomycin A1 (300 nM, 3 h), probed with indicated antibodies.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(J) Seahorse XF Cell Mito stress test for analysis of mitochondrial function in Irgm1+/+ and Irgm1-/- mouse BMDM cells. The experiments were performed using the XF24 extracellular flux analyzer, and the flow chart showed the measurement of oxygen consumption rate (OCR)",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(K) Representative confocal images of control and IRGM siRNA transfected THP-1 cells stained with CMXRos red dye.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(L) Flow cytometry analysis of control siRNA and IRGM siRNA transfected THP-1 cells stained with CMXRos red dye (10 nM, 30 mins). (M) Graph depicts the normalized mean fluorescent intensity of control and IRGM knockdown THP-1 cells stained with CMXRos.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(N) Representative dot plot showing flow cytometry analysis of control and IRGM siRNA knockdown THP-1 cells stained with JC-1 dye (2 µM, 30 mins). At low mitochondrial membrane potential, JC-1 is predominantly a monomer that yields green fluorescence, whereas at mitochondrial membrane potential the dye aggregates producing a red to orange colored emission.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(P) Representative flow cytometry analysis of control and IRGM siRNA transfected THP-1 cells stained with MitoSox red dye (1µM, 20 min). The percentage of control and IRGM knockdown cells with increased red fluorescence (mitochondrial ROS generation) is depicted.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(Q) Representative flow cytometry analysis of control and IRGM siRNA transfected THP-1 cells stained with CellRox-green and CellRox-orange dye (1µM, 30 min).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(A) Representative confocal images of Irgm1+/+ and Irgm1-/- mouse BMDMs processed for IF analysis with Tom20 (red) and dsDNA (green) antibody.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(B) Representative STED microscopy images of control THP-1 cells processed for IF analysis with cGAS (green), dsDNA (red), and Lamin B1 (cyan) antibodies. (C) The graph depicts the percentage of cells with micronuclei in control siRNA and IRGM siRNA knockdown THP-1 cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(D-E) Representative STED microscopy images of Irgm1-/- mouse BMDMs (D) transfected with mCherry-cGAS and immunostained with dsDNA (green) antibody. The white line depicts the periphery of the cells. Scale bar, 3 µm. (E) The graph depicts the percentage of cells with micronuclei in Irgm1+/+ and Irgm1-/- mouse BMDMs.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(F) The qRT-PCR analysis with cytosolic DNA (minus mitochondria) isolated from Irgm1+/+ and Irgm1-/- mouse BMDMs.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(G) The qRT-PCR analysis with cytosolic DNA (minus mitochondria) isolated from control and IRGM siRNA transfected HT-29 cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(H) The qRT-PCR analysis with cytosolic DNA (minus mitochondria) isolated from control or IRGM shRNA or EtBr treated IRGM shRNA HT-29 (Rho0) cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(I) The qRT-PCR analysis with total RNA isolated from control or IRGM shRNA or EtBr treated IRGM shRNA HT-29 (Rho0) cells.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(J) The qRT-PCR analysis with cytosolic DNA (minus mitochondria) isolated from Irgm1+/+ and Irgm1-/- mouse BMDMs transfected with DNase I (15 μg, 6hr).",
    "ncbi_link": "DNase I: 282217
Irgm1: 15944"
  },
  {
    "caption": "(K) The qRT-PCR analysis with RNA isolated from control and IRGM siRNA knockdown THP-1 cells electroporated with DNase I (5 μg, 1hr) as indicated.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(L-M) Representative confocal images of Irgm1+/+ and Irgm1-/- mouse BMDMs processed for IF analysis with (L) dsRNA (green) and Tom20 (red) antibodies. (M) The graph depicts the percentage of Irgm1+/+ and Irgm1-/- mouse BMDMs with dsRNA aggregates.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(N) Representative confocal images of Irgm1-/- mouse BMDMs processed for IF analysis with RIG-I (red) and dsRNA (green) antibodies. Line profile: Co-localization analysis using line intensity profiles.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "Representative confocal images of Irgm1-/- mouse BMDMs processed for IF analysis with (O) Mda5 (red) and dsRNA (green) antibodies Co-localization analysis using line intensity profiles.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "Representative confocal images of Irgm1-/- mouse BMDMs processed for IF analysis with (P) Mda5 (red), dsRNA (green) and Tia1 (blue) antibodies (Scale bar, 3 µm). Line profile: Co-localization analysis using line intensity profiles.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(A) qRT-PCR analysis with total RNA isolated from Irgm1+/+ and Irgm1-/- mouse BMDMs transfected with control siRNA or cGAS siRNA or RIG-I siRNA or cGAS siRNA and RIG-I siRNA as indicated.",
    "ncbi_link": "cGAS: 214763
RIG-I: 230073
Irgm1: 15944"
  },
  {
    "caption": "(B) qRT-PCR analysis with total RNA isolated from HT-29 cells transfected with control siRNA or IRGM siRNA or doubly transfected with IRGM siRNA and cGAS siRNA or IRGM siRNA and RIG-I siRNA or transfected with three siRNAs as indicated.",
    "ncbi_link": "cGAS: 115004
RIG-I: 23586
IRGM: 345611"
  },
  {
    "caption": "(C) qRT-PCR analysis with total RNA isolated from HT-29 cells transfected with control siRNA or IRGM siRNA or doubly transfected with IRGM siRNA and STING siRNA or IRGM siRNA and MAVS siRNA or transfected with all the three siRNAs as indicated.",
    "ncbi_link": "IRGM: 345611
MAVS: 57506
STING: 340061"
  },
  {
    "caption": "(D) qRT-PCR analysis with total RNA isolated from HT-29 cells transfected with control siRNA or IRGM siRNA or doubly transfected with IRGM siRNA and MDA5 siRNA as indicated.",
    "ncbi_link": "MDA5: 64135
IRGM: 345611"
  },
  {
    "caption": "(E) qRT-PCR analysis with total RNA isolated from HT-29 cells transfected with control siRNA or IRGM siRNA or doubly transfected with IRGM siRNA and IRF3 siRNA as indicated.",
    "ncbi_link": "IRF3: 3661
IRGM: 345611"
  },
  {
    "caption": "(F) qRT-PCR analysis with total RNA isolated from HT-29 cells transfected with control siRNA or IRGM siRNA or doubly transfected with IRGM siRNA and STAT1 siRNA or IRGM siRNA and STAT2 siRNA as indicated.",
    "ncbi_link": "IRGM: 345611
STAT1: 6772
STAT2: 6773"
  },
  {
    "caption": "(H) MLL-ENL-expressing  CB cells and MOLM13  cells were transduced with Cas9  together with non-targeting (NT) sgRNA or IMPDH2-targeting sgRNAs (IMPDH2-KO1 and KO2) co-expressing tRFP657. Changes in the frequency of tRFP657+ cells (sgRNA-transduced cells) in cell cultures are shown. Results are normalized to the frequency of tRFP657+ cells at day 4, set to 1.",
    "ncbi_link": "tRFP657: 
Cas9: 69900935
IMPDH2: 3615"
  },
  {
    "caption": "(I) The tRFP657+ cells in (H) were sorted and subjected to  western blotting. The depletion of IMPDH2  protein in MLL-ENL  cells and MOLM13  cells was confirmed by  western blotting.",
    "ncbi_link": "ENL: 4297
MLL: 4297"
  },
  {
    "caption": "(A) Immunoblotting  of the  cord blood cells  and those expressing RUNX1-ETO  or MLL-AF9. The cells were incubated with/without 1 μM MPA  (M) and 100 μM Guanosine  (G) for 24 h.",
    "ncbi_link": "MLL: 4297
AF9: 4300
RUNX1: 861
ETO: 862"
  },
  {
    "caption": "(B) CB-MLL-AF9#2 cells were transduced with a Non-targeting (NT) control and an shRNA targeting p21  (sh-p21). Cells were incubated with/without 1 μM MPA  (M) and 100 μM guanosine  (G) for 24 hours. Total cell lysates were analyzed by western blotting  using the antibodies for p21  and Tubulin.",
    "ncbi_link": "p21: 1026
MLL: 4297
AF9: 4300"
  },
  {
    "caption": "(C) CB-MLL-AF9#2 cells transduced with NT or sh-p21  shRNAs were incubated with MPA  at the indicated concentration for 72 hours. Cell viability assays  were performed using  WST-1 in three technical replicates.",
    "ncbi_link": "p21: 1026"
  },
  {
    "caption": "(D) CB-MLL-AF9#2 cells were transduced by vector control or p53DD (dominant-negative) and were incubated with/without 1 μM MPA  (M) and 100 μM guanosine  (G) for 24 h. Total cell lysates were analyzed by  western blotting  using the antibodies for p53  and Tubulin. Note the elevated levels of endogenous p53  protein (upper arrow) in p53DD (lower arrow)-expressing cells.",
    "ncbi_link": "MLL: 4297
AF9: 4300
p53: 7157"
  },
  {
    "caption": "(F) Mouse bone marrow c-Kit+ cells derived from Trp53-/- mice  were transduced with MLL-AF9-GFP  and were transplanted into mice  to generate p53-deficient (p53-/-) leukemia  cells. GFP+ MLL-AF9 leukemia  cells  were collected from  bone marrows  of vehicle- or  FF-10501-01-treated wild-type and p53-/- leukemic mice. Expression levels of p53  and Tubulin  were assessed by western blotting 24 hours after the treatment.",
    "ncbi_link": "GFP: 
MLL: 214162
AF9: 70122
p53: 22059
Trp53: 22059"
  },
  {
    "caption": "(H) Kaplan-Meier survival curves of p53-/- MLL-AF9 leukemia mice  treated with vehicle or FF-10501-01or  DS-5272 (n = 6 per group). Statistical significance was evaluated by the log-rank test (left). Frequency of GFP+ leukemia  cells in peripheral blood at day 19 (right, n = 6 per group). A two-tailed unpaired t-test was used for the comparison. Data information: All data are shown as mean ± SEM.",
    "ncbi_link": "MLL: 214162
AF9: 70122
p53: 22059"
  },
  {
    "caption": "(B) The TLR-expressing BaκB cells were stimulated with the corresponding TLR ligands (100 ng/mL Pam3CSK4   for TLR2, 100 ng/mL LPS  for TLR4, 10 ng/mL Flagellin      for TLR5, 100 ng/ml R848  for TLR7) with titrating doses of MPA  (1 - 10 μM). GFP  expression was assessed 24 hours after the stimulation.",
    "ncbi_link": "TLR2: 24088
TLR4: 21898
TLR5: 53791
TLR7: 170743"
  },
  {
    "caption": "(C) 293T  cells were transfected with FLAG-tagged TRAF6  and HA-tagged K63-ubiquitin. After 24 hours, these cells were treated with 3 or 10 μM MPA  (M-3 μM or M-10 μM) with/without 100 μM guanosine  (G). IRAK1/4 inhibitor (IRAK1/4 i) was also used as a control. Whole-cell extracts were immunoprecipitated  with anti-FLAG  antibody, and ubiquitinated TRAF6  was detected with anti-HA  antibody.",
    "ncbi_link": "FLAG: 
HA: 
ubiquitin: 
TRAF6: 22034"
  },
  {
    "caption": "(D, Murine bone marrow-derived macrophages (BMDMs) were treated with vehicle, 10 μM MPA  alone (D) N=3 (technical replicates) per group. mRNA levels of TNF-α and  IL-1β were measured by qPCR. Two-tailed unpaired t-tests were used for the comparison in (D). Data information: All data are shown as mean ± SEM.",
    "ncbi_link": "IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "E) Murine bone marrow-derived macrophages (BMDMs) were treated with vehicle, 10 μM MPA  alone or co-treated with vehicle, 10 μM MPA  (M), 100 ng/mL Pam3CSK4  and 100 μM Guanosine  (G) for 4 hours (E), as indicated. N=3 (technical replicates) per group. mRNA levels of TNF-α and IL-1β  were measured by qPCR. Ordinary one-way ANOVA was used for the comparison in (E). Data information: All data are shown as mean ± SEM.",
    "ncbi_link": "IL-1β: 16176
TNF-α: 21926"
  },
  {
    "caption": "(G) MLL-AF9-expressing CB  cells (CB-MLL-AF9#1) were pretreated with 10 μM MPA  for 2 hours and then treated with 1000 ng/mL Pam3CSK4  for 0, 30, 60 Cells were lysed and subjected to SDS-PAGE. Levels of total IκBα, phosphate-p38, total p38  were evaluated by western blotting.",
    "ncbi_link": "MLL: 4297
AF9: 4300"
  },
  {
    "caption": "(E) Example images of brightfield and fluorescently labelled EU (Alexa Fluor 488) of hENT1 and hsvTK cells (PN10567) assayed for global cellular transcription. Scale bars represent 5 µm. (F) Change in EU labelling signal with different lengths of EU incubations, measured by flow cytometry (in PN10597). The mean and standard deviation (SD) of the population medians of at least 200,000 cells in experimental triplicates are shown in black. The dark green line is the OLS linear regression fitted on the mean data between 2 and 12 minutes.",
    "ncbi_link": "ENT1: 2030
TK: 24271467"
  },
  {
    "caption": "(H) Medians of global translation (solid black line) and IQR (shaded area) of cdc25-22 (PN143) cells grown at 30 °C and grouped in length bins of 2 µm. Bins containing more than 30 cells are shown. The solid red lines represent a locally estimated scatterplot smoothing (LOESS) function fitted on the single-cell data.",
    "ncbi_link": "cdc25: 2542632"
  },
  {
    "caption": "(F) Example images of brightfield and EGFP-PCNA fluorescence in CCP∆ EGFP-pcn1 cells (PN6001). The dashed lines in the EGFP-PCNA channel delimit the cell masks generated from the brightfield image. Cells with visible foci in the EGFP-PCNA channel are highlighted in yellow and marked with arrows. Scale bars represent 5 µm.",
    "ncbi_link": "EGFP: 
pcn1: 2540020"
  },
  {
    "caption": "Human brain  slices were infected with HSV-1-GFP  (1˟106 PFU/ml) and  HSV-2-GFP (1˟106 PFU/ml) for 72 h, visualized microscopically",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Human brain  slices were infected with HSV-1-GFP  (1˟106 PFU/ml) and HSV-2-GFP  (1˟106 PFU/ml) for 72 h, and lysed for analysis of GSDME  and vinculin.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(C, SH-SY5Y cells were transfected with CASP2  gRNA-Cas9 RNPs  or AAVS1  gRNA-Cas9 RNPs  and infected with HSV-2. Lysates were isolated 16 h post infection and immunoblotted  for GSDME, CASP2, cleaved caspase 3 (CL-CASP3), cleaved PARP  (CL-PARP) and vinculin  (C).",
    "ncbi_link": "AAVS1: 17
Cas9: 69900935
CASP2: 835"
  },
  {
    "caption": "(H) SH-SY5Y  cells transfected with AAVS1  or CASP2  gRNA-Cas9 RNPs  and infected with HSV-2  for 16 h and examined for morphological  changes by microscopy. Boxes indicate areas highlighted in the zoomed images. Arrows indicate ballooning or syncytial cells.",
    "ncbi_link": "AAVS1: 17
Cas9: 69900935
CASP2: 835"
  },
  {
    "caption": "(B, SH-SY5Y cells transfected with AAVS1  or BID  gRNA-Cas9 RNPs  were infected with HSV-2. Lysates were isolated 16 h post infection and immunoblotted  for GSDME, CL-CASP3  and CL-PARP  (B)",
    "ncbi_link": "AAVS1: 17
BID: 637
Cas9: 69900935"
  },
  {
    "caption": "C) SH-SY5Y cells transfected with AAVS1  or BID  gRNA-Cas9 RNPs  were infected with HSV-2. Lysates were isolated 16 h post infection and assayed for CASP3  activity (C). Data information: All data shown are representative of at least 3 independent experiments. Data are presented as mean ± s.d. in all graphs. ∗∗∗p ≤ 0.001 two-way ANOVA in C",
    "ncbi_link": "AAVS1: 17
BID: 637
Cas9: 69900935"
  },
  {
    "caption": "B) SH-SY5Y cells were infected with HSV-2  (MOI=1) for the indicated time  intervals, and analyzed for mRNA levels of the ER  stress response genes BIP, ATF6  and CHOP  by RT-qPCR (B). Data information: All data shown are representative of at least 3 independent experiments. Data are presented as mean ± s.d. in all graphs. ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001 (Mann-Whitney test, two-tailed in B",
    "ncbi_link": "ATF6: 22926
CHOP: 1649
BIP: 3309"
  },
  {
    "caption": "(L) SH-SY5Y cells transduced with lenti-plasmid BIP  or empty vector control were infected with HSV-2  (MOI=1, 16 h). Lysates were isolated and immunoblotted  for GSDME  and tBID.",
    "ncbi_link": "BIP: 3309"
  },
  {
    "caption": "SH-SY5Y cells were infected with HSV-2 for the indicated time  intervals. Total RNA was analyzed for spliced XBP1  (XBP1s) by  RT-qPCR  Data information: All data shown are representative of at least 3 independent experiments. Data are presented as mean ± s.d. in all graphs. ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001 (Mann-Whitney test, two-tailed in B",
    "ncbi_link": "XBP1: 7494"
  },
  {
    "caption": "(E) SH-SY5Y  cells transfected with AAVS1  or IRE1A  gRNA-Cas9 RNPs  were infected with HSV-2 (MOI=1, 16 h). Lysates  and supernatant  were isolated and immunoblotted  for IRE1α, GSDME, cytochrome c  and HMGB1  release.",
    "ncbi_link": "AAVS1: 17
Cas9: 69900935
IRE1A: 2081"
  },
  {
    "caption": "(B-D) iPSC-derived microglia  cells were treated with the conditioned medium from HSV-2-infected control and GSDME-depleted SH-SY5Y  cells for 8 h. Total RNA was isolated and analyzed for expression of IL6, TNFA, and CXCL10  by RT-qPCR. Data information: All data shown are representative of at least 3 independent experiments. Data are presented as mean ± s.d. in all graphs. ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001 (Two-way ANOVA in B-D",
    "ncbi_link": "CXCL10: 3627
GSDME: 1687
IL6: 3569
TNFA: 7124"
  },
  {
    "caption": "(E-G) Conditioned medium from SH-SY5Y cells with HSV-2  infection (MOI=1, 24 h) was transferred to THP1  cells (WT, STING-/-, MYD88-/-, TRIF-/- and MAVS-/-). Total RNA was isolated 8h later and analyzed for expression of IL6  (E), TNFA  (F), and CXCL10  (G) by  RT-qPCR. Data information: All data shown are representative of at least 3 independent experiments. Data are presented as mean ± s.d. in all graphs. ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001 Wilcoxon matched-pairs test in E-G).",
    "ncbi_link": "CXCL10: 3627
IL6: 3569
MAVS: 57506
MYD88: 4615
STING: 340061
TRIF: 148022
TNFA: 7124"
  },
  {
    "caption": "B. Quantification of PLAs  between BRCA2  and DPP9  in control HeLa  WT cells treated with non-targeting siRNA (siNT) or silenced with the indicated oligos. 300 ng / mL MMC  was added for 24 h. Each dot represents the number of PLA  events in a single cell, from two to seven biological replicates (siNT-MMC  (n = 6), siNT+MMC  (n = 7), siDPP9-MMC  (n = 4), siDPP9+MMC (n = 5), siBRCA2-MMC  (n = 2), siBRCA2+MMC  (n = 3), siFLNA-MMC  (n = 5), siFLNA+MMC  (n = 6), NgtCntrl-MMC  (n = 3), NgtCntrl+MMC  (n = 6)). The number of foci are shown based on their cellular localisation. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (* = p ≤ 0.05, **** = p ≤ 0.0001). C. Representative PLA  images showing close proximity between endogenous DPP9  and endogenous BRCA2  in HeLa WT cells. Exposure of cells to MMC  triggers more PLA  events (white). Phalloidin  (green) stains actin filaments, DAPI  (blue) stains  the nucleus. Scale bar 10 µm. Anti-BRCA2: RRID:AB_2259370, anti-DPP9: RRID:AB_2889071",
    "ncbi_link": "BRCA2: 675
DPP9: 91039
FLNA: 2316"
  },
  {
    "caption": "F.  Co-immunoprecipitation assays showing binding  of BRCA2  and DPP9-SWT. HEK293 DPP9  KO + DPP9WT cells, were treated with 1µg/mL Dox  (24 h) to induce the expression of DPP9-FLAG. DNA damage was induced with 300 nM MMC  treatment for 24h. Control cells do not express DPP9  (- Dox). Bound proteins were eluted with a FLAG  peptide and analysed by Western Blotting (anti-BRCA2: RRID:AB_2259370, anti-DPP9: RRID:AB_731947, anti-FLAG  RRID:AB_262044).",
    "ncbi_link": "FLAG: 
DPP9: 91039"
  },
  {
    "caption": "B.  Pull-down  assay showing direct binding  of purified recombinant DPP9  to a BRCA2  N-terminal1-40 fragment immobilized on HA-beads. The DPP9  inhibitors 1G244  or SLRFLYEG  compete with BRCA21-40HA for interaction  with DPP9. Representative data of three technical replicates is shown. Anti-HA: RRID:AB_2565334, anti-DPP9: RRID:AB_2889071.",
    "ncbi_link": "HA: 
BRCA2: 675"
  },
  {
    "caption": "A-B. Representative  Western Blots  and accompanying graph from more than three biological replicates show that MMC  (300 nM, 24 h) induces a rapid turnover  of endogenous BRCA2  in HeLa  WT cells, which is less pronounced in HeLa  WT cells treated with the proteasome  inhibitor MG132  (100µM), in HeLa DPP9  KD cells and in cells transiently silenced for DPP9  (siDPP9). RAD51  stability is not altered in HeLa DPP9  KD cells. Vinculin  is a loading control for BRCA2, Tubulin  is a loading control for RAD51. Shown images originate from one representative cycloheximide  (CHX) chase assay. The ratios of BRCA2  to Vinculin  and RAD51 to Tubulin  are defined as 100% at time  0 h. Mean ± SEM, data were analysed by a paired two-tailed t-test. (*= p ≤ 0.03). Anti-BRCA2: RRID:AB_2259370, anti-DPP9: RRID:AB_731947, anti-Vinculin: RRID:AB_477629, anti-Tubulin: RRID:AB_628412, anti-RAD51: RRID:AB_1142428.",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "C-D. Representative  Western Blots and graph summarizing results of more than three biological replicates. CHX  chase assays show that the MMC-induced degradation   of BRCA2  is less pronounced in HEK293 DPP9  KO cells as well as in HEK293 DPP9  KO + DPP9-SS729A cells overexpressing an inactive DPP9-S mutant. Expression of DPP9  was induced (+ Dox, 1µg/ml) simultaneously with MMC  (300 nM), 24 h. Cells that were overexpressing the active variant (DPP9-SWT) show similar levels of MMC-induced BRCA2 degradation. RAD51 stability  is not altered by MMC  and is similar in all cell lines. Vinculin  is a loading control for BRCA2, Tubulin  is a loading control for RAD51. Shown images originate from one representative cycloheximide  (CHX) chase assay. The ratios of BRCA2  to Vinculin  are defined as 100% at time  0 h. Mean ± SEM, data were analysed by a paired two-tailed t-test (*= p ≤ 0.03, **= p ≤ 0.002). Antibodies as described in (A-B).",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "F-G. Representative Western Blots  and graphs summarizing CHX  assays from three biological replicates showing that the BRCA2∆MP3-1000 truncation mutant is degraded at a higher rate compared to the untruncated BRCA21-1000. Cells were co-transfected with a GFP  expressing plasmid, as transfection and loading control. Control cells were transfected with GFP  only (U.T). Image originates from one representative experiment. BRCA2-FLAG  signals are related to the transfection and loading control GFP. BRCA2  levels in relation to GFP  were defined as 100 % at time  0 h. Mean ± SEM, data were analysed by a paired two-tailed t-test (*= p ≤ 0.03). Anti-FLAG: RRID:AB_262044, anti-GFP: RRID:AB_641123.",
    "ncbi_link": "GFP: 
BRCA2: 675"
  },
  {
    "caption": "A. Representative immunofluorescence  images of γH2AX  signals (white, RRID:AB_309864) in gki MEF DPP9S729A, showing more γH2AX  in gki MEF DPP9S729A cells following removal of Neocarzinostatin  (NCS), quantification in (B). MEF DPP9S729A and control MEF  cells were treated with 250 ng/mL NCS  for 30 min and allowed to recover for the indicated time-points. γH2AX  signals at time  0, reflect 30 min of NCS  and no recovery time. Nuclei  are shown in blue (DAPI). Scale bar 10 µm. B. Quantification of γH2AX  in gki MEF DPP9S729A and control MEF  cells as described in (A). Signals from more than 1700 cells were quantified per condition per experiment. Mean ± SEM from six biological replicates, each in technical duplicates. Data were analysed by an unpaired two-way ANOVA with Sidak's multiple comparison test (* = p ≤ 0.05, ** = p ≤ 0.01).",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "C. Representative PLA  images of BRCA2-PALB2 PLA  experiments showing more PLA  events (white) in HeLa  cells silenced for DPP9  (siDPP9) with respect to cells treated with non-targeting siRNA (siNT). Phalloidin  (green) stains actin filaments, DAPI  (blue) stains  the nucleus. Scale bar 10 µm. Anti-PALB2: RRID:AB_890607, anti-BRCA2: RRID:AB_2259370.",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "D. Quantification of PLAs  experiments showing more BRCA2-PALB2 PLA events in cells silenced for DPP9  (siDPP9) in comparison to non-targeting controls (siNT). Each dot represents the number of PLA  events in a single cell, from four biological replicates. The technical control samples (NgtCntrl) omitted the BRCA2  antibody. The number of foci is shown based on their cellular localisation. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (**** = p ≤ 0.0001).",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "E. Representative PLA  images of γH2Ax-BRCA2 PLA  experiment showing a reduction in the number of PLA  events (white) between γH2Ax  and BRCA2  in HeLa DPP9  KD cells. Phalloidin  (green) stains actin filaments, DAPI  (blue) stains  the nucleus. Scale bar 10 µm. Anti-γH2Ax: RRID:AB_2118009, anti-BRCA2: RRID:AB_2259370 F. Quantification of PLAs  showing fewer MMC-induced γH2Ax-BRCA2 PLA  events in HeLa DPP9  KD cells, in comparison to HeLa  WT cells. Each dot represents the number of PLA  events in a single cell, from three biological replicates. The technical control samples (NgtCntrl) omitted the γH2Ax  antibody. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (**** = p ≤ 0.0001).",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "A. Representative immunofluorescence  images showing that re-expression of DPP9-SWT leads to an increase in the number of RAD51  foci formed following exposure to MMC  in HEK293 DPP9  KO + DPP9-SWT cells. Expression of DPP9  was induced (+ Dox, 1µg/ml) simultaneously with MMC  (300 nM), 24 h. RAD51  foci are shown in white, nuclei  (DAPI) are shown in blue. Scale bar 10 µm. Anti-RAD51: RRID:AB_1142428. B. Graph showing the number of RAD51  foci following induction of DPP9-SWT expression, compared to uninduced HEK293 DPP9  KO + DPP9WT  cells (-Dox). Induction of HEK293 DPP9  KO + DPP9S729A for expression of DPP9-SS729A did not result in more RAD51  foci. Each dot represents the number of RAD51  foci in a single cell, from three biological replicates. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (**** = p ≤ 0.0001).",
    "ncbi_link": "DPP9: 91039"
  },
  {
    "caption": "Representative images (C, and summarizing graph (D showing the number of RAD51  foci per nucleus  in HeLa  WT cells (C, D) Where stated, cells were treated with control siRNA (siNT) or silenced for BRCA2, and transiently transfected with the BRCA21‑3418 or BRCA23-3418 constructs. Both BRCA2  constructs can rescue the RAD51  foci formation phenotype to the control levels in HeLa  WT cells (C, D). Each dot represents the number of RAD51  foci in a single cell, from three (D) biological replicates. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (**** = p ≤ 0.0001). RAD51  foci are shown in white, nuclei  (DAPI) are shown in blue. Scale bar 10 µm. Anti-RAD51: RRID:AB_1142428; ; anti-BRCA2: RRID:AB_2259370.",
    "ncbi_link": "BRCA2: 675"
  },
  {
    "caption": "Representative images , E) and summarizing graph F) showing the number of RAD51  foci per nucleus  in HeLa DPP9  KD cells (E, F). In HeLa DPP9  KD cells significantly more RAD51  foci were present in cells transfected with BRCA2∆MP3-3418 compared to BRCA2  silenced cells and cells expressing the untruncated BRCA21-3418 (E, F). Each dot represents the number of RAD51  foci in a single cell, from four (F) biological replicates. Data were analysed by a two-way ANOVA, with Tukey's Multiple Comparison test. Shown are Mean ± SEM (**** = p ≤ 0.0001). RAD51  foci are shown in white, nuclei  (DAPI) are shown in blue. Scale bar 10 µm. Anti-RAD51: RRID:AB_1142428; anti-BRCA2: RRID:AB_2259370.",
    "ncbi_link": "BRCA2: 675
DPP9: 91039"
  },
  {
    "caption": "(I) Representative images showing the phospho-AMPK immunolabeling (Pseudo-colored) in low-density cortical neurons on the basal condition and on DHPG treatment for 5 minutes in the presence of scrambled siRNA and in the presence of α-SNAP siRNA. MAP2B immunolabeling was used for identifying neurons and intensity was used for normalization. Scale bar 10μm.",
    "ncbi_link": "α-SNAP: 140673"
  },
  {
    "caption": "(J) Box plot showing the normalized phospho-AMPK intensity distribution across multiple neurons on the basal condition in the presence of scrambled siRNA, on DHPG treatment for 5 minutes in the presence of scrambled siRNA, on the basal condition in the presence of α-SNAP siRNA, on DHPG treatment for 5 minutes in the presence of α-SNAP siRNA. Data points in all groups were normalized to the average of the scrambled siRNA basal group. The box extends from 25th to 75th percentile with the middlemost line representing the median of the dataset. Whiskers range from minimum to maximum data point. *p<0.05, n=29-35 cells per group from 3 independent platings.",
    "ncbi_link": "α-SNAP: 140673"
  },
  {
    "caption": "A Expression patterns of pSEU::SEU-GFP and pWOX5::GFP in the embryos of the indicated genotypes at dermatogen, early globular, and heart stages. White arrows indicate the QC precursor cell, and white dashed lines indicate embryos. Scale bars: 10 µm.",
    "ncbi_link": "GFP: 
SEU: 840981
WOX5: 820297"
  },
  {
    "caption": "B Quantification of pWOX5::GFP GFP fluorescence in wild-type (WT) and seu-3 mutant embryos. Fluorescence intensity at the early globular stage of WT embryos was set to 1. Data Information: In (B) data represent mean ± SD of three independent replicates. n denotes the total number of scored samples. Individual values (black dots) are shown. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
seu: 840981
WOX5: 820297"
  },
  {
    "caption": "C, D Expression pattern of pWOX5::GFP in WT (C) and seu-3 (D) embryos at 5 days after germination (DAG). Scale bars: 20 µm. E Quantification of GFP fluorescence in the QC of pWOX5::GFP transgenic plants, as shown in (C) and (D). Fluorescence intensity was normalized to the WT. Data Information: (E), data represent mean ± SD of three independent replicates. n denotes the total number of scored samples. Individual values (black dots) are shown. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
seu: 840981
WOX5: 820297"
  },
  {
    "caption": "F RT-qPCR analysis of the relative expression levels of WOX5 in WT and seu-3 roots. Total RNA was extracted from 5 mm root tip sections of seedlings at 5 DAG. Data Information: (F) data represent mean ± SD of three independent replicates. n denotes the total number of scored samples. Individual values (black dots) are shown. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "seu: 840981
WOX5: 820297"
  },
  {
    "caption": "L, M Double staining of the QC184 β-glucuronidase (GUS) marker (light blue) and starch granules (dark brown) in WT (L) and seu-3 (M) seedlings at 5 DAG. In white arrows indicate the CSCs. Scale bars: 20 μm.",
    "ncbi_link": "seu: 840981"
  },
  {
    "caption": "N, O Expression pattern of J2341 in WT (N) and seu-3 (O) seedlings at 5 DAG. P, Q Expression pattern of CS9227 in WT (P) and seu-3 (Q) seedlings at 5 DAG. In white arrows indicate the CSCs. Scale bars: 20 μm.",
    "ncbi_link": "seu: 840981"
  },
  {
    "caption": "A-C Expression pattern of pWOX5::GFP in WT (A), scr-3 (B) and plt1-4 plt2-2 (C) at 5 DAG. D Quantification of GFP fluorescence in the QC of pWOX5::GFP transgenic seedlings, as shown in (A-C). GFP signal intensity in each genotype was normalized relative to that in the WT. Data information: In (D) n denotes the total number of scored samples. Individual values (black dots) are shown. Data represent mean ± SD of three independent replicates. In (D) different lowercase letters indicate significant differences by one-way ANOVA followed by Tukey's multiple comparison test (P < 0.01).",
    "ncbi_link": "GFP: 
plt1: 821632
plt2: 841542
scr: 824589
WOX5: 820297"
  },
  {
    "caption": "E RT-qPCR analysis of the relative expression levels of WOX5 in WT, scr-3, and plt1-4 plt2-2 roots. Total RNA was extracted from 5 mm root tip sections of seedlings at 5 DAG. Data information: In (E) , **P < 0.01 (Student's t-test). Scale bars: 20 µm.",
    "ncbi_link": "plt1: 821632
plt2: 841542
scr: 824589
WOX5: 820297"
  },
  {
    "caption": "K Quantification of GFP fluorescence in the QC of pSCR::GFP and pSCR::GFP-SCR transgenic seedlings, as shown GFP signal intensity of each genotype was normalized relative to that of the WT. Data information (K), n denotes the total number of scored samples. Individual values (black dots) are shown. Data represent mean ± SD of three independent replicates. (K), **P < 0.01 (Student's t-test). Scale bars: 20 µm.",
    "ncbi_link": "GFP: 
SCR: 824589"
  },
  {
    "caption": "A Yeast two-hybrid (Y2H) assays showing the interaction between SEU and SCR. The yeast transformants were plated on synthetic defined (SD) media lacking Leu and Trp (SD/-2) or lacking Ade, His, Leu, and Trp (SD/-4) to assess protein-protein interactions. AD, GAL4 activation domain; BD, GAL4 DNA-binding domain.",
    "ncbi_link": "GAL4: 855828"
  },
  {
    "caption": "C Verification of in vivo interactions between SCR and SEU in N. benthamiana leaves via Co-IP assays. SCR-GFP and SEU-myc were transiently coexpressed in N. benthamiana leaves. Protein samples were immunoprecipitated using anti-myc antibody.",
    "ncbi_link": "GFP: 
myc: 
SCR: 824589
SEU: 840981"
  },
  {
    "caption": "D Co-IP assays of SEU with SCR in Arabidopsis. Protein extracts from WT and SCR-GFP roots were isolated at 5 DAG and immunoprecipitated with anti-GFP antibody.",
    "ncbi_link": "GFP: 
SCR: 824589"
  },
  {
    "caption": "F, G SCR and SEU physically bind to the WOX5 promoter, as shown by ChIP-qPCR analysis. Chromatin was isolated from 5 mm root tip sections of seedlings at 5 DAG, sonicated, and immunoprecipitated using anti-GFP antibody. The precipitated DNA was used as a template for qPCR analysis. A, B, and I indicated the PCR amplicons ACT7, control. Data information: In (F), (G) data represent mean ± SD of three independent replicates. **P < 0.01 (Student's t-test).",
    "ncbi_link": "ACT7: 830841
WOX5: 820297"
  },
  {
    "caption": "H Mutation of the SCR gene impairs the recruitment of SEU to the WOX5 promoter, as shown by ChIP-qPCR analysis. Chromatin was extracted from SEU-GFP and SEU-GFP scr-3 seedlings at 5 DAG and precipitated with anti-GFP antibody. ChIP signals were quantified by qPCR as a percentage of total input DNA. Data information: In (H) data represent mean ± SD of three independent replicates. **P < 0.01 (Student's t-test).",
    "ncbi_link": "GFP: 
SCR: 824589
scr: 824589
SEU: 840981
WOX5: 820297"
  },
  {
    "caption": "I SEU stimulated SCR-mediated WOX5 promoter activation in transient expression assays in N. benthamiana leaves. The pWOX5::LUC reporter was cotransformed with the indicated effector constructs. The pWOX5::LUC activity was normalized relative to the internal control (LUC/Renilla luciferase [REN]). The schematic diagram shows the construct used in the transient expression assays. Arrows indicate promoter regions, and boxes indicate coding sequences. Different lowercase letters indicate significant differences by one-way ANOVA followed by Tukey's multiple comparison test (P < 0.01). Data information: In (I) data represent mean ± SD of three independent replicates. **P < 0.01 (Student's t-test).",
    "ncbi_link": "LUC: 
luciferase: 
SCR: 824589
SEU: 840981
WOX5: 820297"
  },
  {
    "caption": "J-M Representative confocal images of the indicated genotypes at 5 DAG. Scale bars: 20 μm. Insets show the QC region in which the solid white lines indicate the QC of WT, and the dashed white lines indicate the QC of seu-3. (Insets scale bars: 5 μm). N Quantification of GFP signal intensity in the QC of WT and seu-3 seedlings expressing pWOX5::SEU-GFP and pWOX5::SCR-GFP. GFP signal intensity in seu-3 seedlings was normalized relative to the WT. Individual values (black dots) are shown. n denotes the total number of scored samples. Data information: In (N), data represent mean ± SD of three independent replicates. **P < 0.01 (Student's t-test).",
    "ncbi_link": "GFP: 
SCR: 824589
seu: 840981
SEU: 840981
WOX5: 820297"
  },
  {
    "caption": "C SDG4 physically bind to the WOX5 promoter, as shown by ChIP-qPCR analysis. ACT7, control. Data information Chromatin was isolated from 5 mm root tip sections of seedlings at 5 DAG, sonicated, and immunoprecipitated using anti-GFP or anti-H3K4me3 antibodies. The precipitated DNA was used as a template for qPCR analysis. In (C) data represent mean ± SD of three independent replicates. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "ACT7: 830841
WOX5: 820297"
  },
  {
    "caption": "D, E ChIP-qPCR analysis indicating that mutations in SDG4 and SEU genes impair H3K4me3 deposition in the WOX5 promoter. ChIP signal was normalized to the WT. Individual values (black dots) are shown. Data information: Chromatin was isolated from 5 mm root tip sections of seedlings at 5 DAG, sonicated, and immunoprecipitated using anti-GFP or anti-H3K4me3 antibodies. The precipitated DNA was used as a template for qPCR analysis. In (D), (E) data represent mean ± SD of three independent replicates. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "SDG4: 829210
SEU: 840981
WOX5: 820297"
  },
  {
    "caption": "F, G Expression pattern of pWOX5::GFP in the indicated genotypes at 5 DAG. Scale bars: 20 µm. H Quantification of GFP fluorescence in the indicated genotypes expressing pWOX5::GFP. GFP signal intensity in the WT was set to 1. n denotes the total number of scored samples. Data information: In (H) data represent mean ± SD of three independent replicates. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
WOX5: 820297"
  },
  {
    "caption": "I RT-qPCR analysis of the relative expression levels of WOX5 in WT and ashr3-1 roots. Total RNA was extracted from 5 mm root tip sections of seedlings at 5 DAG. Individual values (black dots) are shown. Data information: In (I) data represent mean ± SD of three independent replicates. **P < 0.01, *P < 0.05 (Student's t-test).",
    "ncbi_link": "ashr3: 829210
WOX5: 820297"
  },
  {
    "caption": "I SEU associates with SCR and SDG4 in N. benthamiana leaves, as shown by Co-IP assays. SDG4-myc, SCR-HA, and SEU-GFP were coinfiltrated into N. benthamiana leaves. Protein samples were immunoprecipitated with anti-GFP antibody and immunoblotted with anti-myc and anti-HA antibody. N. benthamiana leaves coinfiltrated with SDG4-myc and SCR-HA were used as a negative control.",
    "ncbi_link": "HA: 
myc: 
GFP: 
SCR: 824589
SDG4: 829210
SEU: 840981"
  },
  {
    "caption": "J Co-IP assays of SCR with SEU and SDG4 in Arabidopsis. Proteins extracted from SDG4-myc and SDG4-myc SCR-GFP plants were immunoprecipitated using anti-GFP antibody, and immunoblotted using anti-myc and anti-SEU antibodies.",
    "ncbi_link": "GFP: 
myc: 
SCR: 824589
SDG4: 829210"
  },
  {
    "caption": "D. The morphology of oocytes and embryos from female patients with MOS variants. The day of oocyte retrieval was defined as day 0. Polar bodies were indicated by black arrows. Scale bar=20 µm.",
    "ncbi_link": "MOS: 4342"
  },
  {
    "caption": "B. The immunofluorescence images show the pERK1/2 (red) dynamics in immature (GV, n=5), mature (MII, n=10), and fertilized oocytes from unidentified control patients (n=6), as well as in mature oocytes from patient 1 carrying homozygous MOSAsn95Lys variants. pERK1/2 activation was inhibited after U0126 treatment (n=6). FITC-α-tubulin (Green) and DAPI (blue) were used for co-staining. Scale bar=10 µm.",
    "ncbi_link": "MOS: 4342"
  },
  {
    "caption": "C. Western blot analysis of the MEK1/2 and ERK1/2 activation after transfection of FLAG-tagged wild-type MOS and identified MOS variants in HEK 293 cells.",
    "ncbi_link": "FLAG: 
MOS: 4342"
  },
  {
    "caption": "F. Immunofluorescence of FLAG (green) and pERK1/2 (grey) in oocytes after injection of different MOS variant mRNAs combined with mCherry mRNAs. The signal of mCherry was directly captured after fixation, with DAPI staining for DNA visualization (blue). (n=over 30 oocytes in each group). Scale bar=10 µm.",
    "ncbi_link": "mCherry: 
MOS: 4342"
  },
  {
    "caption": "A. Immunofluorescence of FLAG (red) and F-actin (gray) in oocytes after microinjection of negative control or mouse Mos siRNAs combined with or without wild-type human MOS or MOS variants mRNAs and culture in medium with 2.5 µM milrinone for 24 h, followed by release to maturation (n=15-20 oocytes each group). Scale bar= 10 µm.",
    "ncbi_link": "Mos: 17451
MOS: 4342"
  },
  {
    "caption": "C. The immunofluorescence of F-actin (red) and TPX2 (green) in WT and Erk1/2oo-/- oocytes, using DAPI (blue) co-staining (n=15-20 oocytes for each group). The zoomed images of F-actin are displayed in gray. Scale bar=10 µm. D. The box plot summarizing the relative intensities of F-actin between control and ERK1/2oo-/- oocytes (n=7-10 oocytes for each group).",
    "ncbi_link": "Erk1: 26417
ERK1: 26417"
  },
  {
    "caption": "E. Representative bright field images showing the morphology of oocytes and embryos from wildtype and ERK1/2oo-/- mice. The MII oocyte, zygote, 2-cell and blastocyst embryos were harvested in vivo at 14, 24, 48, and 96 h post-hCG, respectively (n=3 mice for each timepoints in two groups). Scale bar=100 µm. F, G. Bar graphs shows the blastocyst percentage (F) and fragment percentage (G) in wild-type (n=51) and maternal ERK1/2 deletion embryos (n=63).",
    "ncbi_link": "ERK1: 26417"
  },
  {
    "caption": "H. The bar graphs show the expression levels of selected MOS-regulated decay genes (n=2 or 3 biological replicates).",
    "ncbi_link": "MOS: 4342"
  },
  {
    "caption": "H. Heatmap showing the expression level of selected maternal genes, mitochondrial translation genes and mitochondrial respiratory chain genes regulated by MOS mutation or ERK1/2 inactivation.",
    "ncbi_link": "ERK1: 5595
MOS: 4342"
  },
  {
    "caption": "E. Representative images displaying JC-1 monomers (green), aggregates (red) and bright filed images of GV and MII oocytes from wild-type (WT) and Erk1/2oo-/- oocytes (n=3 mice in each group). Erk1/2oo-/- oocytes exhibited big and multiple polar bodies. Scale bar=100 µm.",
    "ncbi_link": "Erk1: 26417"
  },
  {
    "caption": "F. Confocal images of JC-1 monomers (green) and aggregates (red) of GV and MII oocytes from wild-type (WT) and Erk1/2oo-/- oocytes (n=3 mice in each group). Erk1/2oo-/- oocytes exhibited big and multiple polar bodies, indicated by red arrows. Hoechst 33342 (blue) was co-stained to represent nucleus or chromosome. Scale bar=10 µm.",
    "ncbi_link": "Erk1: 26417"
  },
  {
    "caption": "(D) PY79 (WT) and ET19 (∆sigX) cells were infected with SPP1 at either high (phages:bacteria 1:1) or low (1:20) MOI, and OD600nm was followed at 2 min intervals. Shown is a representative experiment out of 6 biological repeats, and the average values and SD of 8 technical repeats.",
    "ncbi_link": "sigX: 938966"
  },
  {
    "caption": "(E) BDR2637 (Pveg-mCherry) (WT, purple) and ET191 (PrrnE-gfp, ∆sigX) (∆sigX, cyan) cells were mixed, infected with low concentrations (10-8 PFU/ml) of SPP1, placed on an agarose pad and plaque formation was followed by time lapse confocal microscopy. Shown are overlay images from mCherry (purple) and GFP (cyan) signals of the bacterial lawn captured at the indicated time points (hrs). The plaque is seen as a hole formed on the bacterial lawn. Scale bar 100 µm. Corresponds to Movie EV4.",
    "ncbi_link": "gfp: 
mCherry: 
rrnE: 8303206
sigX: 938966
veg: 936744"
  },
  {
    "caption": "(D) BDR2637 (Pveg-mCherry) (WT, purple) and ET261 (∆yueB, PsigX-sigX-gfp) (cyan) cells were mixed, infected with SPP1 at 5:1 (phages:bacteria) MOI, placed on an agarose pad and followed by time lapse fluorescence microscopy. Shown are overlay images from mCherry (purple), SigX-GFP (cyan), and phase contrast (grey), captured at the indicated time points post infection. Scale bar 1 μm.",
    "ncbi_link": "gfp: 
mCherry: 
sigX: 938966
veg: 936744
yueB: 936567"
  },
  {
    "caption": "(B) ET29 (Pveg-mCherry, PIPTG-sigX) (purple) cells were grown in the presence of IPTG and mixed with PY79 (WT) cells. The mixture was infected with SPP1-lysin-yfp 5:1 (phages:bacteria) MOI, placed on an IPTG-containing agarose pad, and followed by time lapse fluorescence microscopy. Shown are overlay images of phase contrast (grey), signal from mCherry labeled cells (purple), and signal from Lysin-SPP1-YFP (cyan), captured at the indicated time points post infection (upper panels). Corresponding signal from Lysin-SPP1-YFP (cyan) is shown separately (lower panels). Arrows highlight the delayed infection of ET29 cells. Scale bar 1 μm.",
    "ncbi_link": "mCherry: 
yfp: 
YFP: 
sigX: 938966
veg: 936744"
  },
  {
    "caption": "(E) OF83 (Ppen-lacIΔ11-cfp) (WT) and ET40 (Ppen-lacIΔ11-cfp, PIPTG-sigX) cells, grown in the presence or absence of IPTG, were infected with SPP1-delX110lacO64 at 5:1 (phages:bacteria) MOI. The formation of LacI-CFP foci on phage DNA was monitored 10 min post infection. Non-infected OF83 cells were used for comparison. Shown are overlay images of phase contrast (grey) and signal from LacI-CFP (cyan). Scale bar 1 µm. (F) Quantification of the experiment described in (E). Shown is the percentage of LacI-CFP foci 10 min post infection of OF83 and ET40 cells by SPP1, with average values and SD (n ≥ 850 cells for each population).",
    "ncbi_link": "cfp: 
CFP: 
delX: 
pen: 
lacI: 59687637
LacI: 59687637
sigX: 938966"
  },
  {
    "caption": "(A) ET28 (PIPTG-sigX) and ET42 (∆dltA, PIPTG-sigX) cells, grown in the presence or absence of IPTG, were infected with SPP1 at 1:20 (phages:bacteria) MOI, and OD600nm was followed at 2 min intervals. Shown is a representative experiment out of 6 biological repeats, with the average values and SD of 8 technical repeats.",
    "ncbi_link": "dltA: 937358
sigX: 938966"
  },
  {
    "caption": "(D) PY79 (WT) and ET41 (ΔdltA) cells were infected with SPP1 (10-6 PFU/ml), spred over an MB agar plate, and plaque diameter was monitored after 20 hrs of incubation. Shown is plaque diameter distributions for each strain (n ≥ 40).",
    "ncbi_link": "dltA: 937358"
  },
  {
    "caption": "(F) AR16 (PrrnE-gfp) (WT, cyan) and ET411 (Pveg-mCherry, ∆dltA) (∆dltA, purple) cells were mixed, infected with low concentrations (10-8 PFU/ml) of SPP1, placed on an agarose pad, and plaque formation was followed by time lapse confocal microscopy. Shown are overlay images from GFP (cyan) and mCherry (purple) signals of the bacterial lawn captured at the indicated time points (hrs). The plaque is seen as a hole formed on the bacterial lawn. Scale bar 150 µm.",
    "ncbi_link": "gfp: 
mCherry: 
dltA: 937358
rrnE: 8303206
veg: 936744"
  },
  {
    "caption": "H1975 cells were treated with 50 μg/ml PM2.5 for 90 days, and the expression levels of TMPRSS2 mRNA were determined by real-time RT‒PCR (A) respectively. (A) p values were determined by one-sample t-test.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "H1975 cells were infected with sh-TMPRSS2 (sh-TMPRSS2-1 and sh-TMPRSS2-2) or empty vector (Vector). The stable clones of TMPRSS2 knockdown cells were analyzed and their ability to perform anchorage-independent growth in soft agar (C). The data shown in (C) represent the means ± SDs from three independent experiments. (C) p values were determined by one-sample t-test.",
    "ncbi_link": "TMPRSS2: 50528"
  },
  {
    "caption": "A-C H1299 cells were transfected with TMPRSS2-HA or the empty vector (Vector). After 48 h, the transfected cells were assayed for the expression of TMPRSS2 (A) and for the induction of IL18 by qRT‒PCR (B) and Western blotting (C). The results shown in (A, C are from one of three similar experiments. β-actin was used as the loading control.",
    "ncbi_link": "HA: 
IL18: 3606
TMPRSS2: 7113"
  },
  {
    "caption": "(E) Tadpoles at NF50 were amputated, fixed at the indicated time and then processed for whole mount in situ hybridisation using a probe specific for foxm1. The two last panels show transverse section in the non-regenerating spinal cord (nr) and the regenerate at 3dpa. The red circle highlights the spinal cord and the asterisk the notochord.",
    "ncbi_link": "foxm1: 100492241"
  },
  {
    "caption": "(F) Total RNA was isolated from regenerating tails at indicated time points post amputation, reversed transcribed into cDNA and analysed for foxm1 expression by qPCR, using ef1α as a reference gene. The graph represents the mean +/- SD of three independent experiments. One-way ANOVA with Dunnett's multiple comparisons test was used. * p=0.0149",
    "ncbi_link": "ef1α: 549446
foxm1: 100492241"
  },
  {
    "caption": "(A) NF40 tadpoles with the following genotypes foxm1-/- (mut), foxm1+/- (het) and foxm1+/+ (wt) were amputated and left to regenerate for 7 days. The images show representative tails at 3 and 7 dpa. The white arrowheads indicate the amputation site. (B) Quantification of the rate of regeneration. The ratio of the length of the regenerate to the length that has originally be amputated was compared for the whole tail at 3 and 7 dpa. The graph represents the mean+/-SD of 5 independent experiments from 3 different clutches with at least 5 tadpoles in each experiment. ",
    "ncbi_link": "foxm1: 100492241"
  },
  {
    "caption": "(A) Endogenous FAM134B forms oligomers. FAM134B knockout (KO) or wild type (WT) 293T cells were treated with 1μM of Thapsigargin (Tg) for different time and the cell lysates were prepared and analyzed by Western-blot.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(E, F) Measurement of the intracellular ER-scission activity. U2OS cells transiently expressing EGFP-FAM134B (WT), EGFP-FAM134B (84-233) or EGFP-FAM134B (Δ84-233) at same levels, lysosomal degradation of EGFP-FAM134B was blocked by Bafilomycin A1 (Baf A1) or DMSO. GFP-positive puncta were quantified for each cell in (F). For Each group, at least 30 cells were counted. Scale bars, 10 μm. ***P<0.001, "ns" means no significance, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
FAM134B: 54463"
  },
  {
    "caption": "(G, H) Measurement of the ER-phagy activity. U2OS cells transiently expressing mCherry-EGFP-FAM134B (WT), mCherry-EGFP-FAM134B (84-233) or mCherry-EGFP-FAM134B (Δ84-233) at same levels. ER-phagy is indicated by mCherry-positive but EGFP-negative puncta were quantified for each cell in (H). For mCherry-EGFP-FAM134B (WT), 50 cells were counted (n=50); for mCherry-EGFP-FAM134B (84-233), n=56; for mCherry-EGFP-FAM134B (Δ84-233), n=66. Scale bars, 10 μm. The scale bars in the magnification boxes are 2μm. ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
mCherry: 
FAM134B: 54463"
  },
  {
    "caption": "(I) Lysosomal cleavage of GFP was analyzed by Western blot for the cells co-expressing GFP-SEC61B and FAM134B WT-Flag, FAM134B (84-233)-Flag or FAM134B (Δ84-233)-Flag.",
    "ncbi_link": "Flag: 
GFP: 
FAM134B: 54463
SEC61B: 10952"
  },
  {
    "caption": "(B) Comparison of the self-interaction of FAM134B mono-phosphorylation mutants using co-IP.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(C) Comparison of the self-interaction of FAM134 tri-phosphorylation mutants using co-IP.",
    "ncbi_link": "FAM134: 54463"
  },
  {
    "caption": "(E) Lysosomal cleavage of GFP was analyzed by Western blot for the cells co-expressing GFP-SEC61B and FAM134B (WT)-Flag, FAM134B (SA)-Flag or FAM134B (SD)-Flag.",
    "ncbi_link": "Flag: 
GFP: 
FAM134B: 54463
SEC61B: 10952"
  },
  {
    "caption": "(F, G) Measurement of the intracellular ER-scission activity. FAM134B knockout (KO) U2OS cells was engineered to express EGFP-FAM134B (WT), EGFP-FAM134B (SA) or EGFP-FAM134B (SD) at endogenous levels, lysosomal degradation of EGFP-FAM134B was blocked by Bafilomycin A1 (Baf A1). GFP-positive puncta were quantified for each cell in (G). For control, 25 cells were counted (n=25); For EGFP-FAM134B (WT), n=27; for EGFP-FAM134B (SA), n=29; for EGFP-FAM134B (SD), n=25. Scale bars, 10 μm. ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
FAM134B: 54463"
  },
  {
    "caption": "(H, I) Measurement of the ER-phagy activity. FAM134B knockout (KO) U2OS cells was engineered to express mCherry-EGFP-FAM134B (WT), mCherry-EGFP-FAM134B (S151A) or mCherry-EGFP-FAM134B (S151D) at endogenous levels. Lysosomal mCherry-positive but GFP-negative puncta were quantified for each cell in (I). For mCherry-EGFP-FAM134B (WT), 25 cells were counted (n=25); for mCherry-EGFP-FAM134B (SA), n=23; for mCherry-EGFP-FAM134B (SD), n=21. Scale bars, 10 μm. The scale bars in the magnification boxes are 2 μm. ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
mCherry: 
FAM134B: 54463"
  },
  {
    "caption": "(C) In vitro FAM134B S151 phosphorylation by CAMK2B was detected by Western blot. Recombinant proteins for FAM134BWT and FAM134BS151A were purified from E. coil were incubated with purified CAMK2B by IP in kinase buffer. FAM134B phosphorylation was analyzed by a specific antibody recognizing phos-Serine151 of human FAM134B.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(E) FAM134B S151 phosphorylation in CAMK2B knockdown 293T cells.",
    "ncbi_link": "CAMK2B: 816"
  },
  {
    "caption": "(G, H) Measurement of the ER-phagy activity. U2OS cells transiently expressing mCherry-EGFP-FAM134B (WT) were treated with compounds as indicated. Lysosomal mCherry-positive but GFP-negative puncta were quantified for each cell in (H). For vehicle control, 53 cells were counted (n=53), for Ionomycin, n=56; for EB1089, n=54; for KN-93, n=58. Scale bars, 10 μm. The scale bars in the magnification boxes are 2 μm. ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
mCherry: 
FAM134B: 54463"
  },
  {
    "caption": "(I) FAM134B WT or knockout (KO) U2OS cells were treated with CAMK2 activator Ionomycin (Iono), EB1089 or inhibitor KN93 for 24 hours, Western-blot was performed to analyze the proteins as indicated.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(J) CAMK2B WT or knockdown (KD) U2OS cells were treated with 1 μM Thapsigargin (Tg) to induce ER stress for different time as indicated. Cells were collected and analyzed for proteins as indicated by Western blot.",
    "ncbi_link": "CAMK2B: 816"
  },
  {
    "caption": "(K) GFP-cleavage assay. CAMK2B WT or knockdown (KD) U2OS cells were co-transfected with FAM134B-Flag and GFP-SEC61B, 24 hours post transfection, cells were treated with drugs as indicated and analyzed for GFP-cleavage by Western blot. Note: the levels of Flag-FAM134B, CAMK2B, GFP-SEC61B and Tubulin were analyzed by Western blot using different membranes.",
    "ncbi_link": "Flag: 
GFP: 
CAMK2B: 816
FAM134B: 54463
SEC61B: 10952"
  },
  {
    "caption": "(A) Comparison of the self-interaction of FAM134B WT with mutants as indicated using co-IP. SA-G216R was constructed by simultaneously mutating S149, S151 and S153 to alanine (SA) on the basis of FAM134B-G216R.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(C, D) Measurement of the intracellular ER-scission activity of FAM134B WT, G216R, S151A-G216R and SA-G216R. GFP-tagged FAM134B proteins were expressed in U2OS cells at same levels. The autolyosomal degradation of ER fragments labelled by GFP-FAM134B were blocked by Baf A1 or DMSO. GFP-positive puncta were quantified for each cell in (D). For all of the groups, at least 30 cells were included for quantification; Scale bars, 10 μm. ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "FAM134B: 54463"
  },
  {
    "caption": "(E, F) Measurement of the ER-phagy activity of FAM134BG216R. U2OS cells transiently expressing mCherry-EGFP-FAM134B (WT), mCherry-EGFP-FAM134B (G216R), mCherry-EGFP-FAM134B (S151A-G216R) or mCherry-EGFP-FAM134B (SA-G216R) at same levels. Lysosomal mCherry-positive but GFP-negative puncta were quantified for each cell in (F). For WT, 50 cells were counted (n=50); for G216R, n=55; for S151A-G216R, n=51; for SA-G216R, n=52. Scale bars, 10 μm. The scale bars in the magnification boxes are 2 μm. *P<0.05, ***P<0.001, one-way ANOVA, error bars indicate SEM.",
    "ncbi_link": "EGFP: 
mCherry: 
FAM134B: 54463"
  },
  {
    "caption": "(A,A') Specific expression of FAM134B mRNA (green) in sensory neurons (red) of P4d vGlut2Cre;R26lsl-tdTommouse. Scale bars, 100μm. The white dotted line indicates the dorsal root ganglia (DRG) where sensory neurons are genetically labeled with Tomato. Insets of (a) and (a') are high magnifications of sensory neurons showing the co-localization of FAM134B mRNA and Tomato. Scale bars, 10 μm.",
    "ncbi_link": "tdTom: 
Cre: 2777477
R26: 14910
FAM134B: 54463
vGlut2: 140919"
  },
  {
    "caption": "Cultured sensory neurons from DRGs of E14.5 vGlut2Cre;R26lsl-tdTom embryos were infected with same titers of recombinant lentivirus expressing GFP-FAM134B WT (B), G216R(C), S151A-G216R(D), SA-G216R(E), G216R-ΔLIR (F) respectively. Infected sensory neurons (GFP+/Tom+) are indicated with arrowheads. The nuclei of all cells are shown with DAPI staining. Scale bars, 20 μm.",
    "ncbi_link": "GFP: 
tdTom: 
Cre: 2777477
R26: 14910
FAM134B: 54463
vGlut2: 140919"
  },
  {
    "caption": "Cultured sensory neurons from DRGs of E14.5 vGlut2Cre;R26lsl-tdTom embryos were infected with same titers of recombinant lentivirus expressing G216R supplemented with 5μM KN93 (G) Infected sensory neurons (GFP+/Tom+) are indicated with arrowheads. The nuclei of all cells are shown with DAPI staining. Scale bars, 20 μm.",
    "ncbi_link": "tdTom: 
Cre: 2777477
R26: 14910
vGlut2: 140919"
  },
  {
    "caption": " E-F Western blot analysis of HSP60 and ATP5a, as mitochondrial marker in the indicated knock out MEF cells (with / without the indicated DRP1 variant) after 48h of IU1 treatment. Bar graphs represent mean ± SEM, n= at least 3. Student's t test; ",
    "ncbi_link": "DRP1: 74006"
  },
  {
    "caption": " A-D Wild type MEF (A), Hela (B) and PINK1 KO MEF (C) cells were treated with IU1 (48h, 100 μM) and electron microscope images were evaluated for autophagic vesicle formation. (D) bar graphs represents mean± SEM number of autophagosomes and autolysosome / cell from 3 different set of experiments; at least 40 cells were analysed from each group",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "Electron microscope images of mitochondria from SH-SY5Y e, as indicated in the figure, with / without USP14 inhibition/knock down. Arrow heads in the IU1 treated groups indicate the mitochondrial rupture point. Bar graphs represent mean (± SEM) of percentage ruptured mitochondria from at least 3 different experiments. For cells, total 150-300 mitochondria for the control group and 150-190 mitochondria from the IU1 treated groups were counted",
    "ncbi_link": "USP14: 9097"
  },
  {
    "caption": "Electron microscope images of mitochondria fro MEF WT, MEF PINK1 K as indicated in the figure, with / without USP14 inhibition/knock down. Arrow heads in the IU1 treated groups indicate the mitochondrial rupture point. Bar graphs represent mean (± SEM) of percentage ruptured mitochondria from at least 3 different experiments. For cells, total 150-300 mitochondria for the control group and 150-190 mitochondria from the IU1 treated groups were counted",
    "ncbi_link": "PINK1: 68943
USP14: 59025"
  },
  {
    "caption": "Electron microscope images of mitochondria fro Hela an e, as indicated in the figure, with / without USP14 inhibition/knock down. Arrow heads in the IU1 treated groups indicate the mitochondrial rupture point. Bar graphs represent mean (± SEM) of percentage ruptured mitochondria from at least 3 different experiments. For cells, total 150-300 mitochondria for the control group and 150-190 mitochondria from the IU1 treated groups were counted",
    "ncbi_link": "USP14: 9097"
  },
  {
    "caption": "Electron microscope images of mitochondria fro Drosophila thoracic muscle, as indicated in the figure, with / without USP14 inhibition/knock down. Arrow heads in the IU1 treated groups indicate the mitochondrial rupture point. Bar graphs represent mean (± SEM) of percentage ruptured mitochondria from at least 3 different experiments For flies, more than 200 mitochondria from each group were counted from 5 different experiments",
    "ncbi_link": "USP14: 34387"
  },
  {
    "caption": " D Dopamine content in the fly heads (15 day old) was measured by HPLC and the individual fold change values are represented in the scatter graph. Graphs represent mean± SEM. N= 14, 11 and 11 fly heads for control, PINK1 and PINK1+USP14 KD fly respectively. ANOVA followed by Newman Keuls test ",
    "ncbi_link": "PINK1: 31607
USP14: 34387"
  },
  {
    "caption": " C) Violin plot showing high or low expression levels of MALAT1 in rod photoreceptor clusters. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " D) Distribution of rod photoreceptor populations with high MALAT1 expression (MALAT1-hi) or low MALAT1 expression (MALAT1-lo) in three donor retina samples. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " E) Fluorescent in situ hybridization analysis of human peripheral retina showing heterogeneous levels of MALAT1 expression in the rod photoreceptors located in the outer nuclear layer (ONL). INL: inner nuclear layer; OPL: outer plexiform layer. Scale bar = 20µm. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " D) t-SNE plots showing expression of MALAT1. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " E) Expression pattern of MALAT1 in the rod photoreceptor showing MALAT1-hi (CCA1, CCA10) and MALAT1-lo (CCA0) subpopulations. x-axis depicts normalized transcript levels. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " G) Heatmap of differentially expressed genes between the two MALAT1-hi clusters CCA1 and CCA10. The rows correspond to top 10 genes most selectively upregulated in individual clusters (p< 0.01, Benjamini-Hochberg correction) and the columns show individual cells ordered in CCA1 and CCA10. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " Fluorescent in situ hybridization analysis of the same donor human peripheral retina at different time points post-mortem (7 and 13 hours, Retina 7), showing decreases in MALAT1-hi rod subpopulations in the outer nuclear layer (ONL) at later time point. INL: inner nuclear layer; OPL: outer plexiform layer. Scale bar = 20µm. White arrows indicated MALAT1-hi rod photoreceptors. ",
    "ncbi_link": "MALAT1: 378938"
  },
  {
    "caption": " C) Scatter plots showing expression of OPN1LW/OPN1MW or OPN1SW in individual cone photoreceptors for population C10. The colour depicts expression level for OPN1LW/OPN1MW in individual cells. ",
    "ncbi_link": "OPN1LW: 5956
OPN1MW: 2652
OPN1SW: 611"
  },
  {
    "caption": "E Example images of TIRFM endpoint colocalization imaging. Top panels show CEN DNA (top-left panel, blue circles) or CDEIIIMUT CEN DNA (top-middle panel, blue circles) visualized in lysates that included Cse4CENP‑A-GFP or CEN DNA in lysates that lacked Scm3HJURP (scm3-AID) (top-right panel, blue circles). Middle panels show Cse4CENP‑A-GFP visualized on CEN DNA (middle-left panel) or CDEIIIMUT CEN DNA (center panel) or on CEN DNA in lysates lacking Scm3HJURP (scm3-AID) (middle-right panel) with colocalization shown in relation to blue DNA circles. Bottom panels show overlay of CEN DNA channel (magenta) with Cse4CENP‑A-GFP (green) on CEN DNA (bottom-left panel) or CDEIIIMUT DNA (bottom-middle panel) or on CEN DNA in lysates lacking Scm3HJURP (scm3-AID) (bottom-right panel). Scale bars 3μm. Graph shows quantification of observed colocalization of Cse4 on CEN DNA and on CDEIIIMUT CEN DNA or on CEN DNA in lysates that lacked Scm3HJURP (47 ± 2.9%, 3.5 ± 3.0% and 0.6 ± 0.4% respectively, avg ± s.d. n=4 experiments, each examining ~1,000 DNA molecules from different extracts).",
    "ncbi_link": "HJURP: 851416
Scm3: 851416
scm3: 851416"
  },
  {
    "caption": "B Immunoblot analysis of whole cell extracts from WT, chl4-K13S and okp1-AID cells using indicated antibodies.",
    "ncbi_link": "chl4: 851841
okp1: 853090"
  },
  {
    "caption": "C Example images of TIRFM endpoint colocalization assays. Top panels show visualized Cse4CENP‑A-GFP on CEN DNA in extracts from chl4-K13S (top-left panel) or auxin-treated okp1-AID strains (okp1-AID, top-right panel) with colocalization shown in relation to identified CEN DNA in blue circles. Bottom panels show overlay of CEN DNA channel (magenta) with Cse4CENP‑A-GFP (green), Scale bars 3 μm. D Quantification of Cse4CENP‑A endpoint colocalization with CEN DNA in extracts from WT, chl4-K13S, or okp1-AID genetic backgrounds (19 ± 1.1%, 8 ± 0.7%, 5 ± 0.9%, avg ± s.d. n=4 experiments, each examining ~1,000 DNA molecules from different extracts).",
    "ncbi_link": "chl4: 851841
okp1: 853090"
  },
  {
    "caption": "F Kaplan-Meier analysis of Cse4CENP‑A residence lifetimes on CEN DNA in extracts from WT (blue - median lifetime of 82 s, n=1419 over 3 experiments of ~1000 DNA molecules using different extracts), chl4-K13S (red - median lifetime of 70 s, n=546 over 3 experiments of ~1000 DNA molecules using different extracts) and okp1-AID (purple - median lifetime of 61 s, n=348 over 3 experiments of ~1000 DNA molecules using different extracts) genetic backgrounds. Significant difference (***) between WT extract and chl4-K13S extract residence lifetime plots (two-tailed p-value of 3.4e-5 as determined by log-rank test). No significant difference (n.s.) between chl4-K13S and okp1-AID residence lifetimes in (two-tailed p-value of .40 as determined by log-rank test). 95% confidence intervals indicated (dashed lines), right-censored lifetimes (plus icons) were included and unweighted in survival function estimates.",
    "ncbi_link": "chl4: 851841
okp1: 853090"
  },
  {
    "caption": "B. Rev3l+/+ and Rev3l-/- MEFs were pulse-labelled with EdU for 15min, permeabilized, fixed and stained for EdU  incorporation (green). S phase sub-stages from I to IV were evaluated by visual inspection of the cycling population (>300  EdU+ cells, top panel). Scale bar= 5 μm. Dot plots and pie charts show the relative proportion (percentage of total S) of each sub-stage from I to IV (middle and bottom panel, respectively). Each dot represents the mean of two technical replicates.",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "C. Analysis of the active marks H3K27ac and H3K4me3 and facultative heterochromatin mark H3K27me3 content in early, mid, late and TTR compared to disturbed replicating regions found in Rev3l-/- MEFs. Bar in boxplot represents the median, and red points represents the mean. The limit of the boxes corresponds to the 0.25 to 0.75 quartiles with whiskers extending to the maximum value of 1.5 times the interquartile range. Graphs show data from two biological experiments.",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "D. Relative mRNA levels of four genes involved in development (Hoxb2, 8, 9 and  WT1) were validated through qRT-PCR from  Rev3l+/+ and Rev3l-/- MEFs  samples. The data were normalized to the amount of GAPDH mRNA. Error bars indicate standard error of the mean for three independent experiments. ***, P<0.001 and **, P<0.005 by Student's t-test. E. Relative mRNA levels of genes involved in imprinting (paternal expressed genes: Dlk1and Slc18a4 and maternal expressed genes: Dcn1 and H19) were validated through qRT-PCR from Rev3l+/+ and Rev3l-/- MEFs samples. The data were normalized to the amount of  GAPDH mRNA. Error bars indicate standard error of the mean for three independent experiments. *** P<0.001 by Student's t-test. ",
    "ncbi_link": "Slc18a4: 
Dcn1: 102323///100737///76863///233805///114893
Dlk1: 13386
GAPDH: 14433
H19: 14955
Hoxb2: 103889
Rev3l: 19714
WT1: 22431"
  },
  {
    "caption": "A. Total histones were acid extracted from Rev3l+/+ and Rev3l-/- MEFs. Samples were analyzed by  western-blot  using indicated antibodies specific to histone marks (right panel). An anti-pan H4  or H3 was used as loading control (left panel). Histograms show WT/KO Rev3l  fold change relative to the immunoblot  shown on the top panel (using 1X sample intensity).",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "B. Histone mark levels were examined at selected genes repressed in Rev3l-/- MEFs (Hoxb2, Hoxb8, WT1). Histograms represent enrichment of H3K9me3 and  H3K27me3 at indicated loci assessed by  ChIP-qPCR  in Rev3l+/+ and Rev3l-/- MEFs. Error bars indicate standard error of the mean for three independent experiments.",
    "ncbi_link": "Hoxb2: 103889
Hoxb8: 15416
Rev3l: 19714
WT1: 22431"
  },
  {
    "caption": "C. H3K9me3 and H3K27me3 mark levels were evaluated at selected genes that localized in genomic loci displaying replication timing delay and downregulated in  Rev3l-/- MEFs (FoxG1, GATA6). Histograms represent enrichment of H3K9me3 and H3K27me3 assessed by ChIP-qPCR at indicated loci in Rev3l+/+ and Rev3l-/- MEFs. Error bars indicate standard error of the mean for three independent experiments.",
    "ncbi_link": "FoxG1: 15228
GATA6: 14465
Rev3l: 19714"
  },
  {
    "caption": "G. MEFs cells were transfected with GFP-REV3L761-1029 WT PSVVL or ASAVA mutant and fixed with 4% formaldehyde. The distribution of GFP-REV3L constructs was detected by autofluorescence (green), chromocenters  were visualized by HP1α immunostaining (red) and DNA was  counterstained with DAPI. Scale bar= 10 μm",
    "ncbi_link": "GFP: 
REV3L: 5980"
  },
  {
    "caption": "H. Human 293T cells were transfected with either FH-REV3L700-900, mutant V802D F-H-REV3L700- 900 or empty vector. Forty-eight hours after transfection cell lysates were made and used for immunoprecipitation with HP1 antibody. Western blot  was processed and membranes were immunoblotted with the indicated antibodies.",
    "ncbi_link": "REV3L: 5980"
  },
  {
    "caption": "I. 293T  cells were co-transfected with F-H-REV3L700-900 or empty vector and V5-HP1γ, mutant IY/EE V5-HP1γ  or empty vector. Forty-eight hours after transfection cell lysates were made and used for immunoprecipitation  with α-V5 antibody. After  electrophoresis, samples were  immunoblotted  with anti-HA, anti-HP1γ or anti-α-Tubulin  as indicated.",
    "ncbi_link": "V5: 
HP1γ: 11335
REV3L: 5980"
  },
  {
    "caption": "B. Asynchronous Rev3l+/+ and Rev3l-/- MEFs  were fixed with PFA then subjected to in situ proximity ligation assay  (PLA) using 53BP1  and HP1α antibodies then PLA foci were counted in both cell lines (more than 150 nuclei  for each condition were counted). p-values were calculated by Mann-Whitney test ( ****: p<0.0001). Red lines indicate the mean values. Error bars: SEM. Controls with a single antibody are also shown. Experiments were repeated three times. Representative images are shown. Scale bar= 5 μm.",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "C. Asynchronous Rev3l+/+ and Rev3l-/- MEFs were subjected to PLA  as by using γH2AX  and HP1β antibodies and processed as in (B). p-values were calculated by Mann-Whitney test ( *: p<0.05). Red lines indicate the mean values. Error bars: SEM. Controls with a single antibody are also shown. Three independent experiments were performed.",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "Rev3l+/+ and Rev3l-/- MEFs were incubated with or without 0.23 μM aphidicolin for 24h before metaphase spreading. FISH  was performed using major satellite probe to quantify breaks in pericentromeric regions (F). Representative images of chromosomes showing abnormalities (see arrows) in pericentromeric regions from Rev3l-/- MEFs. Chromosomes were labelled with  DAPI  Error bars indicate standard error of the mean for three independent experiments. Mann-Whitney test (ns: not significant, * p<0.05; *** p< 0.001).",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "A. Asynchronous Rev3l+/+ and Rev3l-/- MEFs were UV-irradiated  at the indicated doses and harvested 6 h or 24 h later. Cell lysates were analyzed by immunoblotting with indicated antibodies. B. Asynchronous Rev3l-/- MEFs  complemented with empty vector (EV) or REV3L were UV-irradiated  at the indicated doses and harvested 6 h or 24 h later. Cell lysates were analyzed by immunoblotting  with indicated antibodies. C ",
    "ncbi_link": "Rev3l: 19714
REV3L: 19714"
  },
  {
    "caption": "Asynchronous Rev3l+/+ and Rev3l-/- MEFs were pulse labelled for 15 min using 10 μM  EdU then UV-irradiated  at 4 J/m2. Cells pre-treated with CSK buffer were fixed and 53BP1, RPA  and RAD51 were detected by immunofluorescence. Representative images in non-irradiated  cells (NI) and quantification of 53BP1  foci in  EdU positive cells at different time points  are shown Scale bar= 10 μm The  number  of cells analyzed is indicated in (n) on each graph. ***p < 0.001 (Kruskal-Wallis test). The presented data are representative of 2 repeats). Bars represent the median ± interquartile range",
    "ncbi_link": "Rev3l: 19714"
  },
  {
    "caption": "F-H. Asynchronous Rev3l-/- MEFs complemented with empty vector (EV) or  REV3L  were processed as in (C). Quantification of 53BP1 foci in  EdU positive cells at different time points is shown (F). Quantification of the intensity of chromatin-bound RPA2 (G) and  RAD51  foci (H) 24 hours after UV-irradiation  was performed. The number of cells analyzed is indicated in (n) on each graph. ***p < 0.001 (Kruskal-Wallis test). The presented data are representative of 2 repeats. Bars represent the median ± interquartile range.",
    "ncbi_link": "Rev3l: 19714
REV3L: 19714"
  },
  {
    "caption": "The violin plot of ACE2 gene expression of all major cell types.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Heatmap of marker genes of 16 cell types identified. The red box highlights the cell type specific expression of ACE2.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "The violin plot of ACE2 gene expression across all cell types.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Volcano plot highlighting proteins significantly enriched (open circles, FDR<0.05) in eNOS-FLAG immunoprecipitates from growth factor-stimulated human endothelial cells; n=3 independent cell batches.",
    "ncbi_link": "FLAG: 
eNOS: 4846"
  },
  {
    "caption": "Nitrite in the cell supernatant of HEK293 cells expressing wild-type (WT), Y657F (YF) or Y657D (YD) eNOS and treated with solvent (Sol) or ionomycin (Io, 1 µmol/L, 15 min); n=6 independent experiments (2-way ANOVA and Bonferroni).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "The FMN/FAD ratio measured in eNOS immunoprecipitates from cells expressing WT, YF or YD eNOS; n=6 independent experiments (1-way ANOVA and Newman-Keuls).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "Pyruvate kinase (PK) activity in FLAG immunoprecipitates from human endothelial cells expressing FLAG-tagged wild-type (WT), Y657F (YF) or Y657D (YD) eNOS; n=6 independent cell batches (1-way ANOVA and Tukey).",
    "ncbi_link": "FLAG: 
eNOS: 4846"
  },
  {
    "caption": "PK activity in eNOS immunoprecipitates from HEK293 cells expressing WT, YF, YD or S633D (SD) eNOS; n=5-9 independent experiments (1-way ANOVA and Bonferroni).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "S-nitrosation of PKM2 in human endothelial cells expressing FLAG-tagged WT or YF eNOS and treated with H2O2 (30 µmol/L) for 15 min; n=8 independent cell batches (Unpaired Student's t test). Dithiothreitol (DTT) was included to demonstrate specificity of the S-NO signal.",
    "ncbi_link": "FLAG: 
eNOS: 4846"
  },
  {
    "caption": "PKM2 S-nitrosation in HEK293 cells expressing YF or YD eNOS and either FLAG-tagged WT PKM2 or a C358S (CS) PKM2 mutant. SNO-FLAG-PKM2 was detected with an anti-FLAG antibody after biotin switch technique; n=4 independent experiments (2-way ANOVA & Bonferroni). DTT treatment was included to demonstrate specificity of the SNO signal.",
    "ncbi_link": "FLAG: 
eNOS: 4846
PKM2: 5315"
  },
  {
    "caption": "PK activity in eNOS immunoprecipitates from HEK293 cells co-expressing YF or YD eNOS and either WT PKM2 or the CS PKM2 mutant; n=6 independent experiments (2-way ANOVA & Bonferroni).",
    "ncbi_link": "eNOS: 4846
PKM2: 5315"
  },
  {
    "caption": "PKM2 enzyme kinetics measured with increasing concentrations of phosphoenolpyruvate (PEP) in eNOS immunoprecipitates from HEK293 cells expressing YF or YD eNOS. The data were fit with the Michaelis-Menten equation to determine Vmax and Km; n=4 independent experiments (2-way ANOVA & Bonferroni).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "Quantification of pentose phosphate pathway (PPP) intermediates; gluconate-6-P (G6P), ribulose-5-P (Rl5P), ribose-5-P (R5P), sedoheptulose-7-P (S7P), fructose-6-P (F6P) and erythrose-4-P (E4P) in human endothelial cells expressing YF or YD eNOS; n=6-8 independent cell batches (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "NADPH/NADP+ and GSH/GSSG ratios in human endothelial cells expressing YF or YD eNOS; n=6-8 independent cell batches (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 4846"
  },
  {
    "caption": "Systolic blood pressure (SBP) in wild-type (WT) and YF-eNOS (YF) mice; n=9 animals per group (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. Phosphorylation of eNOS on Tyr656 in lung lysates from animals treated for 7 days, n=6-7 mice per group (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. Systolic blood pressure (SBP) in WT and YF mice treated for 28 days, n=10 mice per group (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. Acetylcholine (ACh)-induced relaxation of aortic rings from the same animals as in panel B, n=8 mice per group (2-way ANOVA and Bonferroni).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. PKM2 S-nitrosation in lungs from WT and YF mice administered AII for 28 days, n=7-8 mice per group (Unpaired Student's t test). DTT treatment was included to demonstrate specificity of the SNO signal. The blots show non adjacent lanes from the same membranes.",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. NADPH/NADP+ and GSH/GSSG ratios in lungs from WT and YF mice treated with AII for 28 days; n=8-9 mice per group (Unpaired Student's t test).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. 3-Nitrotyrosine (3-NT) levels in lungs from WT and YF mice treated with vehicle (Veh) or AII (AII) for 28 days; n=7-9 mice per group (2-way ANOVA and Bonferroni).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. NADPH/NADP+ and GSH/GSSG ratios in pulmonary endothelial cells from WT and YF mice treated with AII for 30 min; n=8 cell batches (2-way ANOVA and Tukey).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "Wild-type (WT) and YF-eNOS (YF) mice were treated with vehicle (Veh) or angiotensin II (AII, 1.44 mg/kg/day) for up to 28 days. H2O2 levels in pulmonary endothelial cells from WT and YF mice after treatment with AII (1 µmol/L) for 30 min; n=8 cell batches (2-way ANOVA and Tukey).",
    "ncbi_link": "eNOS: 18127"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. Proximity ligation assays showing S-nitrosated PKM2 (yellow) in the RCA and LCA 2 days after ligation. Phalloidin staining (blue) was included to highlight the vessel wall; n=4-5 mice per group (2-way ANOVA and Bonferroni). Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. GSH (green) levels in the RCA and LCA 2 days after ligation. CD31 (red) was included to label endothelial cells. n=4-5 mice per group (2-way ANOVA and Bonferroni). Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. 3-nitrotyrosine (3NT, green) levels in the RCA and LCA 2 days after ligation. CD31 (red) was included to label endothelial cells. n=5 mice per group (2-way ANOVA and Bonferroni). Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. Acetylcholine (ACh)-induced relaxation of the phenylephrine contracted LCA 7 days after ligation, n=7-8 mice per group (2-way ANOVA and Bonferroni). Acetylcholine (ACh)-induced relaxation of the phenylephrine contracted aorta 7 days after ligation, n=7-8 mice per group (2-way ANOVA and Bonferroni).",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- mice were treated with vehicle (Veh) or the PKM2 inhibitor shikonin (SKN, 1.2 mg/kg), subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. GSH (green) levels in the RCA and LCA 3 days after ligation. CD31 (red) was included to label endothelial cells. n=5 mice per group (2-way ANOVA and Bonferroni). Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- mice were treated with vehicle (Veh) or the PKM2 inhibitor shikonin (SKN, 1.2 mg/kg), subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. The right, non-ligated artery (RCA) was used as a control. 3-Nitrotyrosine (3NT, green) levels in the RCA and LCA 3 days after ligation. CD31 (red) was included to label endothelial cells. n=5 mice per group (2-way ANOVA and Bonferroni). Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. ICAM1 and VCAM1 (green) expression in the LCA 2 days after ligation. CD31 (red) was included to label endothelial cells and nuclei are highlighted with DAPI (gray). Comparable images were obtained in 4 additional animals in each group. Scale bars: 50 µm.",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "ApoE-/- (-/-) and ApoEYF (YF) mice were subjected to partial ligation of the left carotid artery (LCA) and given a cholesterol-rich diet. Percentage of neutrophils and monocytes infiltrated into the LCA 7 days after ligation and high cholesterol diet feeding; n=9-10 mice per group (Unpaired Student's t test).",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "Percentage of neutrophils and macrophages infiltrated into the LCA from ApoE-/- mice treated with Veh or SKN (1.2 mg/kg) 7 days after ligation and high cholesterol diet feeding; n=4-6 mice per group (Unpaired Student's t test).",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "Plaque burden in ligated carotid arteries from ApoE-/- (-/-) and ApoEYF (YF) mice fed a high cholesterol diet for 21 days; scale bars: 2 mm. Intimal and medial thickness was determined at four specific locations (proximal, middle 1, middle 2, distal) in cryo-sectioned arteries stained with Oil Red O; scale bars: 200 µm. n=7 mice per group (Unpaired Student's t test).",
    "ncbi_link": "ApoE: 11816"
  },
  {
    "caption": "C. Example of dissected brains (upper panel) and coronal sections (left and right panels) stained with H&E of the indicated genotypes. Note the severe hydrocephaly and ventricular dilation of the lateral ventricle (LV) and third ventricle (TV) in a Gemc1-/- mouse (bottom right panel) compared to a Gemc1+/+ littermate animal (bottom left panel). Periventricular malacia (asterisks) and hippocampal atrophy (arrow) is also evident in the Gemc1-/- sample. Scale bars = 500 µm.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "D. Kaplan Meyer survival curve of a cohort of mice of the indicated genotypes and numbers (n). The study was terminated at 16 months and mice were examined for histology. 97% (31/32) of the Gemc1-/- mice examined to date exhibited hydrocephaly (additional histological examples in Appendix Fig S2).",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "E. RT-QPCR analysis of Gemc1 expression in murine tissues from Gemc1+/+ mice using a Taqman probe. Data is compiled from duplicate samples of 3 male mice per tissue and mean and standard deviation are plotted.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "F. RT-QPCR analysis of Gemc1 in trachea, oviduct and ovary tissue from Gemc1+/+ and Gemc1-/- mice shows that the knockout reduces Gemc1 mRNA to undetectable levels. Mean and standard deviation of duplicate samples from 2 female mice are plotted. Additional examples from other Gemc1-/- tissues are shown in Appendix Fig S1.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "B. Testes from Gemc1-/- mice have strongly reduced cellularity compared to Gemc1+/+ or Gemc1+/- animals, as measured by disaggregation of the tissue and cell counting with a Neubauer Chamber (n=3). Mean and standard deviation are indicated.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "C. Histological analysis of tubules from 6-week-old Gemc1-/- mice revealed thinning of the spermatogenic cell layer and decreased numbers of elongated spermatids. Scale bars = 100 µm (left panels) and 50 µm (right panels).",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "D. Sperm counts from the cauda epididymis of wild type and Gemc1-/- mice revealed no sperm in mice lacking GEMC1 (n=3). Mean and standard deviation are indicated. E. Examples of sperm morphology from spermatocyte spreads from 2 month old mice. Scale bars = 10 µm.",
    "ncbi_link": "GEMC1: 239789
Gemc1: 239789"
  },
  {
    "caption": "F and G. Histological evaluation of the caput epididymis in sagittal (F) and coronal (G) orientation from 2 and 4 month old animals, respectively. Note the absence of luminal spermatozoa in the Gemc1-/- mice compared to wild type. Scale bars = 100 µm (F, left panels) and 50 µm (F, right panels and G).",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "A. Examples of ovaries from Gemc1+/+ (top panels) and Gemc1-/- mice (bottom panels) at 6 weeks of age. Ovaries were smaller in Gemc1-/- mice and contained primarily degenerated antral follicles. A histologically normal antral follicle is indicated in the Gemc1+/+ ovary (top right, black arrow) and degenerated antral follicles with high levels of cell death are indicated in the Gemc1-/- ovaries (bottom right, red arrows). Scale bars = 200 µm (left panels)) and 100 µm (right top panels and right bottom panel respectively). B. Morphological abnormalities in the oviduct of 3-week-old Gemc1-/- mice (right panels) compared to Gemc1+/+ (left panels). A clear lack of cilia (bottom panels) in Gemc1-/- oviducts is observed by H&E staining. Scale bars = 50 µm (top panels).",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "C. Staining of frozen sections of oviduct with antibodies for Ac-tubulin (cilia) and γ-tubulin (basal bodies) reveals normal cilia organization in the wild type oviduct (left) while basal bodies and cilia are not detectable in Gemc1-/- oviducts (right). D. FOXJ1 and E. RFX3 staining that is characteristic of MCCs was clearly evident in Gemc1+/+ oviducts and absent in Gemc1-/- mice. Scale bars = 50 µm (C-E).",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "A. H&E staining of the nasal mucosa of E17.5 embryos of the indicated genotype. Normal respiratory pseudostratified columnar ciliated epithelium is shown in Gemc1+/+ embryos compared to the attenuated, flat columnar to squamous epithelium of Gemc1-/- embryos. Scale bars = 20 µm.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "B. PAS staining (purple) of the nasal mucosa of E18.5 embryos of the indicated genotype. Normal PAS positive goblet cells (inset, red arrows) are interspersed between MCCs (inset, black arrows) with their characteristic goblet or cup-like shape in Gemc1+/+ embryos. The Gemc1-/- mucosa has abundant PAS positive materials that accumulate in the apical borders of almost every columnar epithelial cell (inset, red arrows) and lacks typical goblet cells. Scale bars = 20 µm.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "C. Transmission electron micrographs of cross-sections of adult trachea from Gemc1+/+ animals revealed the presence of secretory cells (SC) and multiciliated cells (MCC). The apical membrane of MCCs accumulated basal bodies (BB) nucleating multiple cilia (C) and microvilli (MV). In the Gemc1-/- airway epithelium, no MCCs are identifiable and only secretory-like cells with MV at the apical surface are detectable. Scale bars = 5µm. Higher magnifications of the boxed regions are shown below, scale bars = 0.5µm.",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "E. Cilia (Ac-tubulin staining) are not detectable in the ependymal cells of 2 month old Gemc1-/- mice (right panel). Choroid plexus (CP) and lateral ventricles (LV) are indicated. Scale bars = 20 µm",
    "ncbi_link": "Gemc1: 239789"
  },
  {
    "caption": "E and F. RT-QPCR analysis of individual genes related to MCC formation in the oviduct (E) and trachea (F) of Gemc1-/- mice compared to wild type littermates, using 18S rRNA as a reference (n=2). Genes examined generally fall into 3 classes: centriole duplication (Cep152, Plk4, Cetn2), Deuterosome mediated centriole expansion (Deup1, Ccdc78, Ccno) and transcription of genes required for MCC differentiation (FoxJ1, Myb, Mcidas).",
    "ncbi_link": "18S: 
Deup1: 234964
Ccdc78: 381077
Ccno: 218630
Cep152: 99100
Cetn2: 26370
FoxJ1: 15223
Gemc1: 239789
Mcidas: 622408
Myb: 17863
Plk4: 20873"
  },
  {
    "caption": "A. GEMC1 interacts with E2F4 and DP1. Western blot of HA or FLAG tagged protein expression in the input lysates are shown in the top panel. FLAGimmunoprecipiation (IP) of GEMC1co-IPs DP1 (α-HA, lane 5) and E2F4 (α- HA, lane 6). The interaction is enhanced upon co-expression of HA tagged E2F4 and DP1 (α-HA, lane 7).",
    "ncbi_link": "E2F4: 1874
GEMC1: 647309
DP1: 7027"
  },
  {
    "caption": "B. GEMC1 interacts with E2F5 but not E2F1. Co-IP of E2F5 (α-HA, lane 3) and E2F5-DP1 (α-HA, lane 6) but not E2F1 or E2F1-DP1 (α-HA, lanes 2 and 5). In the FLAG-IP panels, a short (top) and long (second from top) exposure of the Western are shown.",
    "ncbi_link": "E2F1: 1869
E2F5: 1875
GEMC1: 647309
DP1: 7027"
  },
  {
    "caption": "C. Identification of the domain required for E2F4 interaction. GFP tagged GEMC1 and mutant forms were expressed and IPs were performed against GFP. Wild type GEMC1 (lane 5) or GEMC1 lacking the CC domain (lane 6) pulled down E2F4-DP1. A GEMC1 protein lacking the TIRT domain or GFP alone did not IP E2F4-DP1 (lanes 7, 8).",
    "ncbi_link": "E2F4: 1874
GEMC1: 647309
DP1: 7027"
  },
  {
    "caption": "D. Mutation of the single amino acid analogous that identified in MCIDAS in human RGMC patients (G313D) impairs the interaction with E2F4-DP1 (compare land 5 and 6).",
    "ncbi_link": "MCIDAS: 345643"
  },
  {
    "caption": "E. GEMC1 interacts with Multicilin through its CC domain. Wild type GEMC1 or a mutant lacking the TIRT domain pull down Myc-tagged Multicilin (anti- Myc blot, lanes 4 and 6) while a CC domain mutant does not (anti-Myc blot, lane 5).",
    "ncbi_link": "GEMC1: 647309
Multicilin: 345643"
  },
  {
    "caption": "A. Transient overexpression of GEMC1 leads to increased levels of FOXJ1 and MCIDAS expression (RT-QPCR) in HEK293T cells. Results for MCIDAS are graphed on a smaller scale in the right panel: V = vector and G = GEMC1. The mean and standard deviation of 3 individual experiments in HEK293T cells are graphed. Similar induction of FOXJ1 was observed in U2OS and T98G (Fig EV3).",
    "ncbi_link": "FOXJ1: 2302
GEMC1: 647309
MCIDAS: 345643"
  },
  {
    "caption": "B. Both the CC and the TIRT domain of GEMC1 are required to activate FOXJ1 (RT-QPCR). A corresponding Western blot showing relative expression levels of the mutant GFP tagged GEMC1 variants is shown from HEK293T cells. The mean and standard deviation of 3 individual experiments in HEK293T cells are graphed. Similar results were also observed in U2OS (Fig EV3).",
    "ncbi_link": "FOXJ1: 2302
GEMC1: 647309"
  },
  {
    "caption": "C. Activation of FOXJ1 by GEMC1 is inhibited by the co-expression of Geminin (compare 3rd and 4th lanes). Example Western blot is shown below. Results graphed are the mean and standard deviation of 3 individual experiments in HEK293T cells.",
    "ncbi_link": "GEMC1: 647309
Geminin: 51053"
  },
  {
    "caption": "D. Co-expression of GEMC1 and Multicilin results in similar levels of FOXJ1 expression (measured by RT-QPCR) as Multicilin alone in HEK293T cells. The mean and standard deviation of 4 individual experiments in HEK293T cells are graphed.",
    "ncbi_link": "FOXJ1: 2302
GEMC1: 647309
Multicilin: 345643"
  },
  {
    "caption": "E and F. The activation of FOXJ1 by GEMC1 is partially dependent on Multicilin. HEK293T cells were transfected with a control siRNA (siC) or 2 different siRNAs against MCIDAS (si1 and si2) prior to being transfected with GFP or GFP-GEMC1 expression vectors. Relative MCIDAS (E) and FOXJ1 (F) expression levels were assessed by RT-QPCR. The mean and standard deviation of a representative experiment performed in triplicate is graphed. An additional experiment is presented in Fig EV3.",
    "ncbi_link": "FOXJ1: 2302
GEMC1: 647309
MCIDAS: 345643
Multicilin: 345643"
  },
  {
    "caption": "(A) Motility assay of C.c. ΔpseI cells expressing predicted Leg or Pse synthases (LegI or PseI, in yellow or red, respectively) from Plac on pSRK-Gm. Overnight cultures were spotted on PYE soft (0.3%) agar plates with gentamycin and IPTG (0.5 mM) and incubated for 3 days at 30°C. Only predicted PseI-like synthase coding sequences (CDSs) restore motility of the C.c. ΔpseI cells. Note that the predicted synthases labeled in white do not share similarities with LegI or PseI of C. jejuni. Motility assays are representative of three independent experiments.",
    "ncbi_link": "pseI: 
LegI: 
PseI: "
  },
  {
    "caption": "(B) Immunoblot of cell extracts from cells in (A) probed with antibodies to C. crescentus FljK (FljKCc). The migration of flagellins in ΔpseI cells is shifted towards lower molecular mass suggesting that post-translational modification of flagellin is defective in ΔpseI mutant. Molecular sizes are indicated by the blues lines (in kDa). Bs: Brevundimonas subvibrioides, Bl: Brevundimonas lutea, Bv: Brevundimonas viscosa, Dv: Dermabacter vaginalis, Li: Leptospira interrogans, Tp: Treponema pallidum, Td: Treponema denticola, AbACICU: Acinetobacter baumannii ACICU, AbLUH: Acinetobacter baumannii LUH, AbLAC: Acinetobacter baumannii LAC-4, Lp: Legionella pneumophila, PaY82: Pseudomonas aeruginosa Y82, PaPAPS475: Pseudomonas aeruginosa PAPS475, Sj: Shewanella japonicum, Basu: Bacillus subtilis, Ks: Kurthia sibirica, Cb: Clostridium botulinum, Gk: Geobacillus kaustophilus, Mh: Moorella humiferrea, Myco: Mycobacterium sp. KS0706, HrrPV6: Halorubrum sp. PV6, Ms: Methanobrevibacter smithii. All the genes come from synthetic fragments codon optimized for E. coli (except the synthase CDS from Gk that is codon optimized for C.c.). Empty carets indicate the position of modified (glycosylated) flagellin, whereas filled carets mark unmodified flagellin. Yellow boxes indicate PseI functional orthologs. Immunoblots are representative of at least two independent experiments.",
    "ncbi_link": "pseI: 
PseI: 71695428"
  },
  {
    "caption": "(A) and (B) Motility assays of WT, ΔlegI (A) and ΔflmG (B) B.s. cells. Overnight cultures of WT and mutants harboring the empty pSRK-Gm vector (+Plac) or the corresponding complementing plasmid were spotted on PYE soft agar plates with gentamycin and IPTG (0.5 mM) and incubated for 7 days at 30°C. Motility assays are representative of three independent experiments. The same original picture was used to generate Figs 3B and EV2C.",
    "ncbi_link": "legI: 
flmG: "
  },
  {
    "caption": "(F) Flagellum length measurements determined by TEM of WT and mutants B.s. cells: WT, ΔlegX (ΔBresu_3267), ΔlegB (ΔBresu_3266) expressing legX in trans from Plac on a plasmid, ΔlegH (ΔBresu_0506), ΔlegI (ΔBresu_0507), ΔflmG (ΔBresu_2406) and ΔlegI ΔflmG. Box plots represent the distribution of the flagellum lengths. The cross indicates the average length, the central band indicates the median, the upper and lower sides of the box indicate the upper and lower quartiles, respectively, and the whiskers indicate the minimum and the maximum length measured. Twenty-five independent flagella were measured different cells (biological replicates) for each strain from TEM images.",
    "ncbi_link": "Bresu_0506: 
Bresu_3266: 
Bresu_3267: 
legH: 
legI: 
legX: 
Bresu_0507: 
Bresu_2406: 
flmG: 
legB: 
Plac: "
  },
  {
    "caption": "(A) Motility assays of B.s. ΔlegI cells complemented with LegI-type (yellow) or PseI-type (red) synthases expressed from Plac on pSRK-Gm. Motility assays are representative of three independent experiments.",
    "ncbi_link": "legI: 
LegI: 
PseI: "
  },
  {
    "caption": "(B) Immunoblots probed with antibodies to FljKCc, revealing the cell extracts levels of flagellin in B.s. ΔlegI derivatives shown in (A). The blue lines represent the migration of the molecular size standards (in kDa). Bl: Brevundimonas lutea, Bv: Brevundimonas viscosa, Dv: Dermabacter vaginalis, Li: Leptospira interrogans, Tp: Treponema pallidum, Td: Treponema denticola, AbACICU: Acinetobacter baumannii ACICU, AbLUH: Acinetobacter baumannii LUH, AbLAC: Acinetobacter baumannii LAC-4, Lp: Legionella pneumophila, PaY82: Pseudomonas aeruginosa Y82, PaPAPS475: Pseudomonas aeruginosa PAPS475, Sj: Shewanella japonicum, Basu: Bacillus subtilis, Ks: Kurthia sibirica, Cb: Clostridium botulinum, Gk: Geobacillus kaustophilus, Mh: Moorella humiferrea, Myco: Mycobacterium sp. KS0706, HrrPV6: Halorubrum sp. PV6, Ms: Methanobrevibacter smithii. All the genes come from synthetic fragments codon optimized for E. coli (except the synthase CDS from Gk that is codon optimized for C.c.). Empty carets indicate the position of modified (glycosylated) flagellin, whereas filled carets mark unmodified flagellin. Red boxes indicate LegI functional orthologs. Immunoblots are representative of at least two independent experiments.",
    "ncbi_link": "legI: 
LegI: 66489939"
  },
  {
    "caption": "(A) Motility assays of WT B.s. and ΔBresu_3266 (ΔlegB) cells expressing Bresu_3266 (LegB), Bresu_3267 (LegX) or Bresu_3266-Bresu_3267 (LegB-LegX, Bresu_3266-67) from Plac on plasmid pSRK-Gm. Motility assays are representative of three independent experiments. (D) Motility assay of WT B.s. and ΔBresu_0506 (ΔlegH) cells complemented with a plasmid expressing Bresu_0506 (LegH) from Plac on pSRK-Gm. Motility assays are representative of three independent experiments.",
    "ncbi_link": "Bresu_0506: 
Bresu_3266: 
Bresu_3267: 
legB: 
LegB: 
legH: 
LegH: 
LegX: "
  },
  {
    "caption": "(A) Motility assay of ΔBresu_3267 (ΔlegX) B.s. cells compared to WT B.s. cells harbouring the empty pSRK-Gm vector (+Plac) or a complementing derivative with PtmE/LegX orthologs from C. jejuni (Cj), Tanerella forsythia (Tf) or P. aeruginosa NMI1897 (PaNMI). Motility assays are representative of three independent experiments.",
    "ncbi_link": "legX: 
Bresu_3267: 
LegX: 
PtmE: 905621"
  },
  {
    "caption": "(B) Immunoblots probed with anti-FljKCc antibodies from cell lysates (cells) and supernatants (SN) of WT B.s. and ΔBresu_3267 (ΔlegX) cultures harbouring either the empty pSRK-Gm vector (+Plac) or a complementing plasmid expressing different PtmE/LegX orthologs from C. jejuni (Cj), Tanerella forsythia (Tf) or P. aeruginosa NMI1897 (PaNMI). Molecular size standards are indicated by the blue lines with the corresponding value in kDa. Empty carets indicate the position of modified (glycosylated) flagellin, whereas filled carets mark unmodified flagellin. Immunoblots are representative of two independent experiments.",
    "ncbi_link": "legX: 
Bresu_3267: 
LegX: 
PtmE: 905621"
  },
  {
    "caption": "(B) Anti-FljKCc immunoblot analyses of whole cell lysates (cells) from C. crescentus (C.c.) mutant cultures expressing fljKBssyn (codon optimized for E. coli) and flmGBs from the replicative pMT463 plasmid, in the presence or absence of a compatible integrative plasmid carrying a legBs synthetic operon (pXGFP4-legBs) and in the presence or absence of an additional compatible replicative plasmid carrying Bresu_3267 (pMT375). In the presence of pXGFP4-legBs (integrated at the xylX locus) and pMT375-Bresu_3267, FljKBssyn migration is shifted toward higher molecular mass, indicative of glycosylation. Note that in the C.c. Δfljx6 background, the six flagellin-encoding genes have been deleted and the protein detected by the antibodies only corresponds to FljKBssyn. The legBs synthetic operon (in red) is composed of Bresu_3266, Bresu_0765, Bresu_0506, Bresu_3264, Bresu_0507 (legI) and Bresu_3265. Molecular masses are indicated in kDa by the blue lines. Empty carets indicate the position of modified (glycosylated) flagellin, whereas filled carets mark unmodified flagellin. Asterisk indicates a modification of flagellin by FlmGBs that does not require Pse or Leg. Immunoblots are representative of at least two independent experiments.",
    "ncbi_link": "Bresu_0506: 
Bresu_0507: 
Bresu_3267: 
legI: 
Bresu_0765: 
Bresu_3264: 
Bresu_3265: 
Bresu_3266: 
flj: 
fljK: 
FljK: 
flmG: 
FlmG: "
  },
  {
    "caption": "(C) Anti-FljKCc immunoblot analyses of whole cell lysates from C. crescentus mutant cultures expressing FlmGCc, FlmGBs and FlmGCc-Bschim chimera from the replicative pSRK-Gm plasmid (Plac) in the presence of a compatible integrative plasmid carrying a legBs synthetic operon (pXGFP4-legBs) and in the presence or absence of an additional compatible replicative plasmid carrying Bresu_3267 (pMT375). Molecular masses are indicated in kDa by the blue lines. Empty carets indicate the position of modified (glycosylated) flagellin, whereas filled carets mark unmodified flagellin. Immunoblots are representative of at least two independent experiments.",
    "ncbi_link": "Bresu_3267: 
FlmG: "
  },
  {
    "caption": "(A) Representative Western Blot analysis of the endogenous p150Glued co-immunoprecipitated with EB1 in shCTL or shSTIM1 ECs (left) and its quantification by normalized densitometry (right). Negative control (CTL) was performed incubating cell lysate with protein A- or G-Sepharose and empty mouse IgG. Results are the average ± SD of three independent assays. shCTL value of each biological replicate was normalized on itself and so shSTIM1 experimental value. Results were analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL and shSTIM1 p≤ 0,05 *.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(D) Representative Western Blot analysis of increasing amount of GST-STIM1 (cytoplasmic domain) pulled down by Cap-Gly-CC1-p150Glued-V5-coated beads, in absence or presence of FLAG-EB1 C-terminal. Colors label the protein as in (c). Negative control was performed using equal amount of empty GST protein, together with Cap-Gly-CC1-p150Glued.",
    "ncbi_link": "FLAG: 
GST: 
V5: 
EB1: 22919
STIM1: 6786"
  },
  {
    "caption": "(E) Representative Western Blot analysis of mCherry-p150Glued WT co-immunoprecipitated with GFP-STIM1 WT, NN, ΔCC1-3/WT (ΔCC/WT) or ΔCC1-3/NN (ΔCC/NN) in co-transfected HEK 293T cells. Negative control (CTL) was performed incubating cell lysate from HEK 293T co-transfected with an empty GFP vector together with mCherry-P150Glued WT with pre-cleared protein A or G-Sepharose and the rabbit GFP antibody. Below, its quantification by normalized densitometry. Results are the average ± SD of three independent assays. The value of P150Glued co-immunoprecipitated with GFP-STIM1 WT from each biological replicate was normalized on itself and so those immunoprecipitated with GFP-STIM1 NN, ΔCC/WT or ΔCC/NN. Results were analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for STIM1 WT and NN p> 0.05 not significant (ns), for STIM1 WT and ΔCC/WT p> 0.05 not significant (ns) and for STIM1 WT and ΔCC/NN p≤ 0,05 *.",
    "ncbi_link": "GFP: 
mCherry: 
STIM1: 6786"
  },
  {
    "caption": " (F) Representative Western Blot analysis of GST-STIM1 (cytoplasmic domain) pulled down by Cap-Gly-CC1-p150Glued-V5-coated beads, in presence of FLAG-EB1 C-terminal WT or ΔY. Negative control was performed using equal amount of empty GST protein, together with Cap-Gly-CC1-p150Glued. ",
    "ncbi_link": "FLAG: 
GST: 
EB1: 22919
STIM1: 6786"
  },
  {
    "caption": " (G) Confocal microscopy analysis of wild-type ECs, transiently transfected with GFP-STIM1 WT or, NN or ΔCC1-3/WT (ΔCC/WT) together with mCherry-P150Glued. Scale bar = 10 μm. Right insets are shown to highlight MT-bound p150Glued+ punctae (arrows), colocalized with STIM1. Scale bar = 5 μm. (H) Average number of the mCherry-P150Glued+ punctae in the same cells as in (g). Counts are the average ± SEM of three independent experiments for a total of 150 punctae (30 cells). Results were analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for STIM1 WT and NN p≤ 0,001 *** and for STIM1 WT and ΔCC/WT p> 0.05 not significant (ns). (I) Co-localization analysis of mCherry-P150Glued with GFP-STIM1 WT, NN or ΔCC1-3/WT (ΔCC/WT), transiently co-transfected in ECs, as in (g). Results are the average ± SEM of three independent experiments for a total of 150 punctae (30 cells) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for STIM1 WT and NN p≤ 0,001 *** and for STIM1 WT and ΔCC/WT p> 0.05 not significant (ns). ",
    "ncbi_link": "GFP: 
mCherry: 
P150Glued: 13191
STIM1: 6786"
  },
  {
    "caption": "(A) Confocal microscopy images of ECs silenced with a control siRNA (siCTL) or one targeting STIM1 (siSTIM1) and stained for endogenous LAMP-1 (in green) to visualize LEs and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(B) Distribution of size, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are from three independent experiments for a total of 249 endosomes (15 siCTL cells) and 441 endosomes (13 siSTIM1 cells). In the right inset, the cumulative distribution used for the Kolmogorov-Smirnov test, p≤ 0,001 ***, is shown. The p-value refers to the rejection of the null hypothesis in favor of the alternative hypothesis that siCTL LE distribution has longer tail than siSTIM1 LE one.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(C) Average number, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are the average ± SEM of three independent experiments for a total of 249 late endosomes in 15 siCTL cells (16 ± 2 endosomes per cell) and 441 late endosomes in 13 siSTIM1 cells (34 ± 3 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(D) Distribution of distance to nucleus, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are from three independent experiments for a total of 249 late endosomes in 15 siCTL cells (16 ± 2 endosomes per cell) and 441 late endosomes in 13 siSTIM1 cells (34 ± 3 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(E) Confocal microscopy images of ECs silenced with a control shRNA (shCTL) or one targeting STIM1 (shSTIM1), rescued for GFP expression alone (shCTL/GFP and shSTIM1/GFP) or for GFP- STIM1 WT (shSTIM1/GFP-STIM1 WT), GFP- STIM1 NN (shSTIM1/GFP-STIM1 NN) or GFP- STIM1 AA (shSTIM1/GFP-STIM1 AA) and stained for endogenous LAMP-1 (in red) to visualize LEs and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm.",
    "ncbi_link": "GFP: 
STIM1: 6786"
  },
  {
    "caption": " (F) Upper panel, Distribution of distance to nucleus, normalized on cell size, quantified by image (as in e) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are from of two independent experiments for a total of 436 late endosomes in 13 shCTL/GFP cells (34 ± 6 endosomes per cell), 1452 late endosomes in 12 shSTIM1/GFP cells (121 ± 13 endosomes per cell) and 498 late endosomes in 10 shSTIM1/GFP-STIM1 WT cells (50 ± 5 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 *** (orange) and for shSTIM1/GFP and shSTIM1/GFP-STIM1 WT p≤ 0,001 *** (green). Lower panel, Distribution of distance to nucleus, normalized on cell size, quantified by image (as in e) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are from of two independent experiments for a total of 498 late endosomes in 10 shSTIM1/GFP-STIM1 WT cells (50 ± 5 endosomes per cell), 1057 late endosomes in 11 shSTIM1/GFP-STIM1 NN cells (96 ± 12 endosomes per cell) and 346 late endosomes in 10 shSTIM1/GFP-STIM1 AA cells (35 ± 2 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for shSTIM1/GFP-STIM1 WT and shSTIM1/GFP-STIM1 NN p≤ 0,05 * (orange) and for shSTIM1/GFP-STIM1 NN and shSTIM1/GFP-STIM1 AA p≤ 0,05 * (green). ",
    "ncbi_link": "GFP: 
STIM1: 6786"
  },
  {
    "caption": " (G) Average size, normalized on cell size, quantified by image (as in e) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are the average ± SEM of two independent experiments for a total of 436 late endosomes in 13 shCTL/GFP cells (34 ± 6 endosomes per cell), 1452 late endosomes in 12 shSTIM1/GFP cells (121 ± 13 endosomes per cell), 615 late endosomes in 12 shSTIM1/GFP-STIM1 WT cells (51 ± 5 endosomes per cell), 1278 late endosomes in 12 shSTIM1/GFP-STIM1 NN cells (106 ± 15 endosomes per cell) and 506 late endosomes in 12 shSTIM1/GFP-STIM1 AA cells (42 ± 7 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 ***, for shCTL/GFP and shSTIM1/GFP-STIM1 WT p> 0.05 not significant (ns), for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 NN p≤ 0,001 ***, for shSTIM1/GFP and shSTIM1/GFP-STIM1 NN p≤ 0,001 *** and for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 AA p> 0.05 not significant (ns). ",
    "ncbi_link": "GFP: 
STIM: 6786
STIM1: 6786"
  },
  {
    "caption": " (H) Average number, normalized on cell size, quantified by image (as in e) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of LAMP-1+ endosomes. Results are the average ± SEM of two independent experiments for a total of 436 late endosomes in 13 shCTL/GFP cells (34 ± 6 endosomes per cell), 1452 late endosomes in 12 shSTIM1/GFP cells (121 ± 13 endosomes per cell), 615 late endosomes in 12 shSTIM1/GFP-STIM1 WT cells (51 ± 5 endosomes per cell), 1278 late endosomes in 12 shSTIM1/GFP-STIM1 NN cells (106 ± 15 endosomes per cell) and 506 late endosomes in 12 shSTIM1/GFP-STIM1 AA cells (42 ± 7 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 ***, for shCTL/GFP and shSTIM1/GFP-STIM1 WT p≤ 0,001 ***, for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 NN p≤ 0,05 *, for shSTIM1/GFP and shSTIM1/GFP-STIM1 NN p≤ 0,01 ** and for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 AA p> 0.05 not significant (ns). ",
    "ncbi_link": "GFP: 
STIM: 6786
STIM1: 6786"
  },
  {
    "caption": " (A) Confocal microscopy images of ECs silenced with a control siRNA (siCTL) or one targeting STIM1 (siSTIM1) and stained for endogenous Rab5 (in green) and EEA-1 (in red) to visualize EEs and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": " (B) Average size, normalized on cell size, of EEA-1+ endosomes as in a. Results are the average ± SEM of three independent experiments for a total 4483 early endosomes in 18 siCTL cells (299 ± 33 endosomes per cell) and 2454 early endosomes in 13 siSTIM1 cells (189 ± 17 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": " (C) Average number, normalized on cell size, of EEA-1+ endosomes as in a. Results are the average ± SEM of three independent experiments for a total 4483 early endosomes in 18 siCTL cells (299 ± 33 endosomes per cell) and 2454 early endosomes in 13 siSTIM1 cells (189 ± 17 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,01 **. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": " (D) Distribution of distance to nucleus overtime, normalized on cell size, quantified by image (data correspond to movies EV1 and EV2) segmentation (see Material and Method, Live imaging experiments) of Rab5+ endosomes, appearing for 60 seconds. Results are from three independent experiments for a total of 903 early endosomes in 18 siCTL cells (50 ± 5 endosomes per cell) and 935 early endosomes in 20 siSTIM1 cells (47 ± 9 endosomes per cell). Data are analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,01 **. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": " (A) Confocal microscopy images of ECs silenced with a control shRNA (shCTL) or one targeting STIM1 (shSTIM1), rescued for GFP expression alone (shCTL/GFP and shSTIM1/GFP) or for GFP-STIM1 WT (shSTIM1/GFP-STIM1 WT) or GFP- STIM1 NN (shSTIM1/GFP-STIM1 NN) and stained for endogenous EEA-1 (in red) to visualize EEs and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm. ",
    "ncbi_link": "GFP: 
STIM1: 6786"
  },
  {
    "caption": " (B) Upper panel, Distribution of distance to nucleus, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from two independent experiments for a total of 830 early endosomes in 13 shCTL/GFP cells (64 ± 6 endosomes per cell), 719 early endosomes in 10 shSTIM1/GFP cells (60 ± 6 endosomes per cell) and 820 early endosomes in 12 shSTIM1/GFP-STIM1 WT cells (68 ± 6 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 *** (orange) and for shSTIM1/GFP and shSTIM1/GFP-STIM1 WT p≤ 0,001 *** (green). Lower panel, Distribution of distance to nucleus, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from two independent experiments for a total of 820 early endosomes in 12 shSTIM1/GFP-STIM1 WT cells (68 ± 6 endosomes per cell) and 400 early endosomes in 12 shSTIM1/GFP-STIM1 NN cells (33 ± 7 endosomes per cell) and analyzed a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "GFP: 
STIM1: 6786"
  },
  {
    "caption": " (C) Average size, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are the average ± SEM of two independent experiments for a total 830 early endosomes in 13 shCTL/GFP cells (64 ± 6 endosomes per cell), 719 early endosomes in 10 shSTIM1/GFP cells (60 ± 6 endosomes per cell), 820 early endosomes in 12 shSTIM1/GFP-STIM1 WT cells (68 ± 6 endosomes per cell) and 400 early endosomes in 12 shSTIM1/GFP-STIM1 NN cells (33 ± 7 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,001 ***, for shCTL/GFP and shSTIM1/GFP-STIM1 WT p> 0.05 not significant (ns), for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 NN p≤ 0,001 *** and for shSTIM1/GFP and shSTIM1/GFP-STIM1 NN p≤ 0,05 *. ",
    "ncbi_link": "GFP: 
STIM: 6786
STIM1: 6786"
  },
  {
    "caption": " (D) Average number, normalized on cell size, quantified by image (as in a) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are the average ± SEM of two independent experiments for a total 830 early endosomes in 13 shCTL/GFP cells (64 ± 6 endosomes per cell), 719 early endosomes in 10 shSTIM1/GFP cells (60 ± 6 endosomes per cell), 820 early endosomes in 12 shSTIM1/GFP-STIM1 WT cells (68 ± 6 endosomes per cell) and 400 early endosomes in 12 shSTIM1/GFP-STIM1 NN cells (33 ± 7 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for shCTL/GFP and shSTIM1/GFP p≤ 0,01 **, for shCTL/GFP and shSTIM1/GFP-STIM1 WT p> 0.05 not significant (ns), for shSTIM1/GFP-STIM WT and shSTIM1/GFP-STIM1 NN p≤ 0,001 *** and for shSTIM1/GFP and shSTIM1/GFP-STIM1 NN p≤ 0,001 ***. ",
    "ncbi_link": "GFP: 
STIM: 6786
STIM1: 6786"
  },
  {
    "caption": "(A) mRNA levels of KIFC1, KIFC2 and KIFC3 in ECs. Values are normalized on GAPDH mRNA levels. Results are the average ± SD of three independent experiments and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for KIFC1 and KIFC2 p≤ 0,01 ** and for KIFC1 and KIFC3 p≤ 0,05 *.",
    "ncbi_link": "GAPDH: 2597
KIFC1: 3833
KIFC2: 90990
KIFC3: 3801"
  },
  {
    "caption": "(B) Representative Western Blot analysis of endogenous KIFC1 and STIM1 proteins (both normalized on total tubulin levels) in ECs silenced with a control siRNA (siCTL) or one targeting KIFC1 (siKIFC1) or two control siRNAs (siCTLsiCTL) or two targeting KIFC1 and STIM1 (siKIFC1siSTIM1). Results are the average ± SD of three independent experiments and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for siCTL and siKIFC1, KIFC1 expression p≤ 0,001 ***, STIM1 expression p> 0.05 not significant (ns) and for siCTLsiCTL and siKIFC1siSTIM1, KIFC1 expression p≤ 0,01 **, STIM1 expression p≤ 0,05 *.",
    "ncbi_link": "KIFC1: 3833
STIM1: 6786"
  },
  {
    "caption": " (C) Confocal microscopy images of ECs silenced with a control siRNA (siCTL) or one targeting KIFC1 (siKIFC1) or one targeting STIM1 (siSTIM1) or two targeting both (siKIFC1siSTIM1) and stained for endogenous EEA-1 (in green) and LAMP-1 (in red) to visualize EEs and LEs, respectively, and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm. ",
    "ncbi_link": "KIFC1: 3833
STIM1: 6786"
  },
  {
    "caption": " (D) Distribution of distance to nucleus, normalized on cell size, quantified by image (as in c) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes in siCTL and siKIFC1 ECs. Results are from three independent experiments for a total of 4091 early endosomes in 19 siCTL cells (215 ± 20 endosomes per cell) and 2275 early endosomes in 20 siKIFC1 cells (114 ± 10 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "KIFC1: 3833"
  },
  {
    "caption": " (E) Distribution of distance to nucleus quantified by image (as in c) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from three independent experiments for a total of 4091 early endosomes in 19 siCTL cells (215 ± 20 endosomes per cell), 2275 early endosomes in 20 siKIFC1 cells (114 ± 10 endosomes per cell) and 3257 early endosomes in 18 siKIFC1/siSTIM1 cells (181 ± 14 endosomes per cell). Data are analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for siCTL and siKIFC1 ECs p≤ 0,001 *** (orange) and for siKIFC1 and siSTIM1/siKIFC1 ECs p≤ 0,001 *** (green). On the right-hand side of the plot, colored bands represent the average cell diameter, significantly changing throughout the conditions. Data are analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,01; Bonferroni for siCTL and siKIFC1 ECs p> 0.05 not significant (orange ns) and for siKIFC1 and siSTIM1/siKIFC1 ECs p≤ 0,01 ** (green). ",
    "ncbi_link": "KIFC1: 3833
STIM1: 6786"
  },
  {
    "caption": " (C) Representative Western Blot analysis of endogenous HOOK1 or HOOK3 and total tubulin proteins in ECs, silenced with a control siRNA (siCTL) or one targeting HOOK1 (siHOOK1; on the left) or one targeting HOOK3 (siHOOK3; on the right). ",
    "ncbi_link": "HOOK1: 51361
HOOK3: 84376"
  },
  {
    "caption": " (D) Confocal microscopy images of ECs silenced with a control siRNA (siCTL) or one targeting HOOK1 (siHOOK1) or one targeting HOOK3 (siHOOK3) or two targeting both (siHOOK1siHOOK3) and stained for endogenous EEA-1 (in green) and LAMP-1 (in red) to visualize EEs and LEs, respectively, and DAPI (in blue) to highlight the nucleus. The yellow line is drawn to define cell periphery. Scale bar = 20 μm. On the right, inset panels to highlight respective perinuclear and peripheral area of the cell. Scale bar = 5 μm. ",
    "ncbi_link": "HOOK1: 51361
HOOK3: 84376"
  },
  {
    "caption": " (E) Distribution of distance to nucleus, normalized on cell size, quantified by image (as in d) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from three independent experiments for a total of 1193 early endosomes in 12 siCTL cells (99 ± 9 endosomes per cell) and 1104 early endosomes in 21 siHOOK1 cells (53 ± 4 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "HOOK1: 51361"
  },
  {
    "caption": " (F) Distribution of distance to nucleus, normalized on cell size, quantified by image (as in d) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from three independent experiments for a total of 1193 early endosomes in 12 siCTL cells (99 ± 7 endosomes per cell) and 1282 early endosomes in 22 siHOOK3 cells (58 ± 5 endosomes per cell) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "HOOK3: 84376"
  },
  {
    "caption": " (G) Distribution of distance to nucleus quantified by image (as in d) segmentation (see Material and Method, Confocal microscopy and early/late quantification) of EEA-1+ endosomes. Results are from three independent experiments for a total of 1193 early endosomes in 12 siCTL cells (99 ± 7 endosomes per cell), 1104 EEs in 21 siHOOK1 cells (53 ± 4 endosomes per cell) and 2340 EEs in 19 siHOOK1/siHOOK3 cells (123 ± 11 endosomes per cell) and analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for siCTL and siHOOK1 ECs p≤ 0,001 *** (orange) and for siHOOK1 and siHOOK1/siHOOK3 ECs p≤ 0,001 *** (green). On the right hand side of the plot, colored bands represent the average cell diameter, significantly changing throughout the conditions. Data are analyzed by a parametric two-tailed analysis of variance (ANOVA) with Bonferroni post hoc analysis. ANOVA p≤ 0,001; Bonferroni for siCTL and siHOOK1 ECs p> 0.05 not significant (orange ns) and for siHOOK1 and siHOOK1/siHOOK3 ECs p≤ 0,001 *** (green). ",
    "ncbi_link": "HOOK1: 51361
HOOK3: 84376"
  },
  {
    "caption": " (A) Confocal microscopy images of ECs silenced with a control shRNA (shCTL) or one targeting STIM1 (shSTIM1), to which the pH-sensitive dye pHrodo Green was given and then cells were stained for LAMP-1 (in red) to visualize LEs and DAPI (in blue) to highlight the nucleus. Scale bar = 20 μm. (B) Relative amount of LAMP-1+ LEs positive to the pH-sensitive dye pHrodo (as in a) in shCTL and shSTIM1 ECs. Results are the average ± SEM of three independent experiments for a total of 90 cells (30 cell for experiment) and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,001 ***. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": " (C) Representative Western Blot analysis of endogenous Raptor, total and phospho-Thr389 S6K1 proteins (normalized on total tubulin levels) in ECs silenced with a control shRNA (shCTL) or one targeting STIM1 (siSTIM1). Numbers above each band represent respective N.O.D. average (two biological replicates) quantification. ",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(D) Representative Western Blot analysis of endogenous LC3-I and -II proteins (both normalized on total tubulin levels and represented as ratio LC3-II/LC3-I) in ECs silenced with a control shRNA (shCTL) or one targeting STIM1 (siSTIM1). Results are the average ± SD of three independent experiments and analyzed by a two-tailed heteroscedastic Student's t-test, p≤ 0,01 **.",
    "ncbi_link": "STIM1: 6786"
  },
  {
    "caption": "(A) Confocal microscopy of GFP-TRIM33-overexpressing mESCs  and differentiated cells. Scale bar = 5 µm. (B) Line scans of GFP-TRIM33  and DAPI  fluorescence imaging in each cell context at the position depicted by the white line (from left to right). These line scans were processed by plot profile using image J software. (C) FRAP  assays showing recovery time  of normalized fluorescence signals for GFP-TRIM33  puncta in mESCs. Photobleaching  occurs at t = 5s. Data are the mean ± S.D. of three biological experiments.",
    "ncbi_link": "GFP: 
TRIM33: 51592"
  },
  {
    "caption": "(F) Western blot analysis of TRIM33 interactions  with PML  in lysates of HEK293T cells co-transfected with plasmids encoding Flag-PML  and GFP-TRIM33. GFP-TRIM33  was immunoprecipitated  with anti-GFP  affinity beads and immune complexes were detected using antibodies targeting Flag  and GFP. Protein inputs were detected using antibodies against Flag  and GFP  in the same amount of cell lysates. (n = 3). Data information: All data are from three biological replicates.",
    "ncbi_link": "Flag: 
GFP: 
PML: 5371
TRIM33: 51592"
  },
  {
    "caption": "(H) Lysates from HEK293T  cells co-transfected with plasmids encoding either full length Flag-TRIM33  or the Flag-TRIM33-RBCC domain alone and full-length HA-PML  or the HA-PML-RBCC domain alone immunoprecipitated  with anti-Flag  affinity beads. Protein complexes were detected using antibodies against Flag  and HA. The protein inputs were detected using antibodies against Flag  and HA  in the same amount of cell lysates. (n = 3). Data information: All data are from three biological replicates.",
    "ncbi_link": "Flag: 
HA: 
PML: 5371
TRIM33: 51592"
  },
  {
    "caption": "(A) Representative images of immunofluorescence staining of PML  in WT and Pml  null mESCs. Scale bar = 5 µm.",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(B) Representative  confocal microscopy images of mESCs  overexpressing mCherry-PML  or GFP-PML  (top). Representative confocal microscopy  images of mESCs  overexpressing mCherry-EV or GFP-EV (bottom). Scale bar = 5 µm. (C) FRAP  assays quantifying normalized fluorescence recovery of GFP-PML  signal in mESCs. Photobleaching  occurs at t = 5s. Data are the mean ± S.D. of four biological experiments.",
    "ncbi_link": "GFP: 
mCherry: 
PML: 5371"
  },
  {
    "caption": "K) Representative images of co-localization  assays with GFP-TRIM33  in mESCs Pml  null (K). Scale bar = 5 µm. L) Line scans of GFP-TRIM33 fluorescence imaging in each cell context at the position depicted by the white line (from left to right). These line scans were processed by plot profile using image J software. (M) Column graph of the numbers of GFP-TRIM33  puncta and DAPI  in mESCs.",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(N) Scatter plot of the numbers of GFP-TRIM33  puncta (per cell) in WT and Pml  KO mESCs. (n = 20). (O) Scatter plot of the volume of GFP-TRIM33  puncta (per cell) in WT and Pml  KO mESCs. (n = 20). Data information: In panels (N, O, 20 individual puncta with three biological experiments were analyzed. Significant differences were determined by t-tests. (*p < 0.05, ****p < 0.0001). ",
    "ncbi_link": "Pml: 18854"
  },
  {
    "caption": "(P) Representative images of immunofluorescence staining  of PML  in WT and Trim33  null mESCs. Scale bar = 10 µm. (Q) Scatter plot of the numbers of PML NBs  (per cell) in WT and Trim33  KO mESCs. (n = 20). (R) Scatter plot of the proportion of PML NBs  (per cell) in WT and Trim33  KO mESCs. (n = 20). Data information: In panels Q and R), 20 individual puncta with three biological experiments were analyzed. Significant differences were determined by t-tests. (*p < 0.05, ****p < 0.0001). ",
    "ncbi_link": "Trim33: 94093"
  },
  {
    "caption": "G, H Luciferin  assay of NFAT  activity (G) and Nfatc1  mRNA expression  (H) in J76-NFATRE-luc  and TCR052 cells stimulated with α-human CD3  (OKT3) (1 µgml-1) in the presence of α-human CD28  (1 µgml-1) for 4 h or treated with DSF  (5 µM) for 2 h. The levels of NFAT  activity were normalized with TCR052  cells treated with DMSO  (n = 3). Data information: data are representative of 3 independent experiments, mean ± SD. **P<0.01; ***P<0.001; ****P<0.0001; two-way analysis of variance (ANOVA) in (G, H)].",
    "ncbi_link": "luc: 
Nfatc1: 4772
NFAT: 4772"
  },
  {
    "caption": "I Western blot  analysis of p-CD3ζ, LCK  and p-Zap70  in LCK-deficient cells were infected with the lentivirus  collected from human HEK293T  cells transfected with control plasmid (Control) (1 µg), LCK(WT) (1 µg), or LCK(C20/23S) (1 µg) with psPAX2 (1 µg) and pMD2.G (1 µg) for 48 h followed by treatment with DSF  (5 µM) for 2 h stimulated with α-human CD3  and α-human CD28  for 5 min. Data information: data are representative of I) independent experiments",
    "ncbi_link": "LCK: 3932"
  },
  {
    "caption": "D A heatmap of upregulated genes associated with TCR and T cell activation-related genes in DSF  relative to that in DMSO. One column indicates one sample in each condition (n = 3). Data information: data are representative of 3 independent experiments",
    "ncbi_link": "TCR: 21577///110067///110066///21473"
  },
  {
    "caption": "A. GFP-Snc1-PEM protein accumulates in atg1Δ, atg8Δ, and atg11Δ mutant cells. Lysates were prepared from wild type (WT), ypt1-1 (for comparison), atg1Δ, atg8Δ, and atg11Δ mutant cells transformed with a 2μ plasmid expressing GFP-Snc1-PEM from the TPI promoter. The level of GFP-Snc1-PEM was determined using immunoblot analysis with anti-GFP antibodies. The bands were quantified and increase in the protein level in mutant versus the WT cells is shown under the blot and adjusted to the G6PDH loading control.",
    "ncbi_link": "PEM: 
atg1: 852695
atg11: 856162
atg8: 852200
Snc1: 851203
ypt1-1: 850505"
  },
  {
    "caption": "B. GFP-Snc1-PEM protein accumulates in aberrant ER structures in atg1Δ, atg8Δ, and atg11Δ mutant cells. The ER-marker Sec61 was tagged with mCherry in strains from panel A, and the cells were examined by live-cell microscopy. Shown from left to right: DIC, GFP, mCherry, merge, % cells with intracellular GFP-Snc1-PEM (number of cells with internal GFP-Snc1-PEM / number of cells visualized), and % cells in which intra-cellular Snc1-PEM co-localizes with Sec61.",
    "ncbi_link": "atg1: 852695
atg11: 856162
atg8: 852200"
  },
  {
    "caption": "C. UPR is induced in atg1Δ, atg8Δ, and atg11Δ mutant cells. Cells from panel A were transformed with a second plasmid that expresses β-gal from a UPR promoter. UPR was determined and expressed as % of the WT response.",
    "ncbi_link": "atg1: 852695
atg11: 856162
atg8: 852200"
  },
  {
    "caption": "D-E. Unlike deletion of Atg11, deletion of other known selective Atgs required for the CVT pathway (Atg19), mitophagy (Atg32) and pexophagy (Atg36), does not result in increase of GFP-Snc1-PEM protein level (D",
    "ncbi_link": "Atg11: 856162
Atg19: 854072
Atg32: 854660
Atg36: 853254"
  },
  {
    "caption": "D-E. Unlike deletion of Atg11, deletion of other known selective Atgs required for the CVT pathway (Atg19), mitophagy (Atg32) and pexophagy (Atg36), does not result in increase of GFP-Snc1-PEM protein level (D), intra-cellular accumulation of GFP-Snc1-PEM, (E),",
    "ncbi_link": "Atg11: 856162
Atg19: 854072
Atg32: 854660
Atg36: 853254"
  },
  {
    "caption": "D-E. Unlike deletion of Atg11, deletion of other known selective Atgs required for the CVT pathway (Atg19), mitophagy (Atg32) and pexophagy (Atg36), does not result in increase of GFP-Snc1-PEM protein level (D), intra-cellular accumulation of GFP-Snc1-PEM, (E), and induction of the UPR response (F). Wild type (WT), atg19Δ, atg11Δ, atg32Δ, and atg36Δ mutant cells overexpressing GFP-Snc1-PEM were analyzed as described for panels A-C, respectively. E. Shown from left to right: DIC, GFP, and % cells with intracellular Snc1-PEM structures. +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "Atg11: 856162
atg11: 856162
atg19: 854072
Atg19: 854072
atg32: 854660
Atg32: 854660
atg36: 853254
Atg36: 853254"
  },
  {
    "caption": "A-C. While the level of overexpressed GFP-Snc1-PEM is increased in atg9∆ and atg2∆, but not atg18∆, mutant cells, it does not accumulate in aberrant structures and does not induce UPR. Wild type (WT), atg9∆, atg18∆, and atg2∆ mutant cells overexpressing GFP-Snc1-PEM were analyzed as described for Fig 1A-1C, respectively. The tested phenotypes: the level of GFP-Snc1-PEM protein (A),",
    "ncbi_link": "PEM: 
atg18: 850577
atg2: 855479
atg9: 851406"
  },
  {
    "caption": "A-C. While the level of overexpressed GFP-Snc1-PEM is increased in atg9∆ and atg2∆, but not atg18∆, mutant cells, it does not accumulate in aberrant structures and does not induce UPR. Wild type (WT), atg9∆, atg18∆, and atg2∆ mutant cells overexpressing GFP-Snc1-PEM were analyzed as described for Fig 1A-1C, respectively. The tested phenotypes: the level of GFP-Snc1-PEM protein (A), accumulation of GFP-Snc1-PEM in aberrant structures (B)",
    "ncbi_link": "PEM: 
atg18: 850577
atg2: 855479
atg9: 851406"
  },
  {
    "caption": "A-C. While the level of overexpressed GFP-Snc1-PEM is increased in atg9∆ and atg2∆, but not atg18∆, mutant cells, it does not accumulate in aberrant structures and does not induce UPR. Wild type (WT), atg9∆, atg18∆, and atg2∆ mutant cells overexpressing GFP-Snc1-PEM were analyzed as described for Fig 1A-1C, respectively. The tested phenotypes: the level of GFP-Snc1-PEM protein (A), accumulation of GFP-Snc1-PEM in aberrant structures (B), and induction of the UPR response (C,atg1∆ is shown as a positive control).",
    "ncbi_link": "PEM: 
atg1: 852695
atg18: 850577
atg2: 855479
atg9: 851406"
  },
  {
    "caption": "D-G. Atg9 is epistatic to Atg11 in macro-ER-phagy. ATG9 was deleted in wild type and atg11∆ mutant cells and the effects of overexpression of GFP-Snc1-PEM were determined in the single and double mutants as described in Fig 1 legend. D. Deletion of ATG9 in wild type (WT) or atg11∆ mutant cells results in an increase of GFP-Snc1-PEM protein level similar to the increase in atg11∆ mutant cells.",
    "ncbi_link": "PEM: 
Atg11: 856162
atg11: 856162
Atg9: 851406
ATG9: 851406"
  },
  {
    "caption": "E. Deletion of ATG9 in wild type or atg11∆ mutant cells results in an increase of intracellular GFP-Snc1-PEM fluorescence. However, only ~20% of the atg9∆ single-, and atg9∆ atg11∆ double-mutant cells accumulate GFP-Snc1-PEM in aberrant structures, as compared with ~75% of atg11∆ mutant cells. Shown from top to bottom: DIC, GFP, % cells with aberrant intracellular GFP-Snc1-PEM structures, ratio of GFP-Snc1-PEM fluorescence inside/PM (30 cells were analyzed for each strain).",
    "ncbi_link": "PEM: 
atg11: 856162
ATG9: 851406
atg9: 851406"
  },
  {
    "caption": "F. UPR is induced in atg11∆, but not in atg9∆ single- and atg9∆ atg11∆ double-mutant cells overexpressing GFP-Snc1-PEM.",
    "ncbi_link": "PEM: 
atg11: 856162
atg9: 851406"
  },
  {
    "caption": "G. UPR can be induced in atg9∆ single-, and atg9 atg11∆ double-mutant cells overexpressing GFP-Snc1-PEM by tunicamycin. +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "PEM: 
atg11: 856162
atg9: 851406"
  },
  {
    "caption": "A-C.ATG9 was deleted in ypt1-1, WT and sec12ts mutant cells and the effect of overexpression of GFP-Snc1-PEM was determined in single and double mutant cells. Experiments were performed as described for Fig 1A-1C, respectively. A. Snc1-PEM is increased ~3 fold in atg9∆ and sec12ts as compared to ~20 fold in ypt1-1 mutant cells. Importantly, atg9∆ is epstatic to the ypt1-1, but not to the sec12ts, mutation. Left, immuno-blot analysis, increase of the protein level in mutant versus the WT cells is shown under the blot; right, a bar graph summarizing the quantified data",
    "ncbi_link": "ATG9: 851406
atg9: 851406
sec12ts: 855760
ypt1-1: 850505"
  },
  {
    "caption": ". Whereas deletion of ATG9 in ypt1-1 mutant cells results in three fold lower accumulation of GFP-Snc1-PEM in aberrant structures (85% to 27%), its deletion in sec12ts mutant cells results in two fold increased accumulation (~40% to ~80%). Shown from top to bottom: DIC, GFP, and % cells with intracellular Snc1-PEM structures.",
    "ncbi_link": "ATG9: 851406
sec12ts: 855760
ypt1-1: 850505"
  },
  {
    "caption": "C. Deletion of ATG9 in ypt1-1 mutant cells overexpressing Snc1-PEM results in ~3.5 lower UPR (p-value<0.0005), but a slightly increased UPR in sec12ts mutant cells (p-value = 0.05).",
    "ncbi_link": "ATG9: 851406
sec12ts: 855760
ypt1-1: 850505"
  },
  {
    "caption": "D. Atg9 is present on aberrant ER structures that accumulate in ypt1-1 mutant cells. WT and ypt1-1 mutant cells expressing Atg9-mCherry from the chromosome and GFP-Snc1-PEM from a 2μ plasmid were analyzed by live-cell microscopy. Whereas in WT cells (top), the GFP-Snc1-PEM localizes to the cell membrane and Atg9-mCherry to intracellular puncta, the two proteins co-localize in 100% of the ypt1-1 mutant cells (bottom) that accumulate intracellular GFP-Snc1-PEM structures (~80%). Shown from left to right: DIC, GFP, mCherry, merge, % cells with intracellular Snc1-PEM, and % cells with co-localization (number of cells with observed phenotype / total number of cells analyzed).",
    "ncbi_link": "Atg9: 851406
ypt1-1: 850505"
  },
  {
    "caption": "E. GFP-Snc1-PEM is delivered to the vacuole for degradation in sec12ts mutant cells. Accumulation of GFP-Snc1-PEM in vacuoles of sec12ts mutant cells, with and without deletion of the vacuolar protease Pep4, was determined using the FM4-64 dye, which labels the vacuolar membrane. Deletion of PEP4 in sec12ts mutant cells results in an increase percent of cells in which GFP-Snc1-PEM accumulates inside the vacuole (from 8% to 100%). Shown from left to right: DIC, GFP, FM4-64 (vacuolar membrane), merge, % cells with aberrant GFP-Snc1-PEM structures, % cells with GFP-Snc1-PEM outside vacuole, and % cells with GFP-Snc1-PEM inside the vacuole. +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "PEP4: 855949
Pep4: 855949
sec12ts: 855760"
  },
  {
    "caption": "A. The ypt1-1 mutation is epistatic to vps21∆ in ER-phagy. yDsRed-Snc1-PEM was overexpressed in WT, vps21∆, ypt1-1 and ypt1-1vps21∆ double mutant cells that also expressed the autophagosomal marker yEGFP-Atg8. Cells were analyzed by live-cell microscopy. Shown from left to right: DIC, DsRed, GFP, merge, % cells Atg8 dots, number of Atg8 dots per cell, and % cells in which the Atg8 dots co-localize with Snc1-PEM. About 50% of WT and 85% of vps21∆ mutant cells contain ~1 dot of Atg8 representing the AP. Importantly, in ~70% of the vps21∆ mutant cells Snc1-PEM co-localizes with the APs, as compared to ~4% in WT cells. In contrast, ~90% ypt1-1 and ypt1-1vps21∆ mutant cells contain three APs per cell, and Snc1-PEM does not co-localize with them. Arrows point to co-localization; arrowheads point to either Atg8 dots or GFP-Snc1-PEM that do not co-localize.",
    "ncbi_link": "Atg8: 852200
vps21: 854256
ypt1-1: 850505"
  },
  {
    "caption": "The following effects of overexpression of GFP-Snc1-PEM in WT and ypt1-1 mutant cells, without and with ire1Δ or hac1Δ, were analyzed as described for Fig 1A-1C, respectively: protein level (B), accumulation of GFP-Snc1-PEM in aberrant structures (C), and UPR induction (D). B. Deletion of either Ire1 or Hac1 does not affect the level of Snc1-PEM accumulation in WT or ypt1-1 mutant cells.",
    "ncbi_link": "PEM: 
hac1: 850513
ire1: 856478
ypt1-1: 850505"
  },
  {
    "caption": "C. Deletion of either Ire1 or Hac1 does not affect the percent of WT and ypt1-1 mutant cells that accumulate aberrant intra-cellular Snc1-PEM. Shown from top to bottom: DIC, GFP, and % cells with intracellular Snc1-PEM structures.",
    "ncbi_link": "PEM: 
Hac1: 850513
Ire1: 856478
ypt1-1: 850505"
  },
  {
    "caption": "D. Deletion of either Ire1 or Hac1 obliterate UPR in both WT and ypt1-1 mutant cells. +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "Hac1: 850513
Ire1: 856478
ypt1-1: 850505"
  },
  {
    "caption": "A-C. Overexpressed Snq2-GFP accumulates in the ER and induces UPR in ypt1-1 mutant cells. Snq2-yEGFP was overexpressed in WT and ypt1-1 mutant cells and the following effects were analyzed as described for Fig 1A-1C, respectively: increase in the level of Snq2-yEGFP protein (A)",
    "ncbi_link": "Snq2: 851574
ypt1-1: 850505"
  },
  {
    "caption": "A-C. Overexpressed Snq2-GFP accumulates in the ER and induces UPR in ypt1-1 mutant cells. Snq2-yEGFP was overexpressed in WT and ypt1-1 mutant cells and the following effects were analyzed as described for Fig 1A-1C, respectively: increase in the level of Snq2-yEGFP protein (A), accumulation of Snq2-yEGFP in aberrant ER structures (B),",
    "ncbi_link": "Snq2: 851574
ypt1-1: 850505"
  },
  {
    "caption": "A-C. Overexpressed Snq2-GFP accumulates in the ER and induces UPR in ypt1-1 mutant cells. Snq2-yEGFP was overexpressed in WT and ypt1-1 mutant cells and the following effects were analyzed as described for Fig 1A-1C, respectively: increase in the level of Snq2-yEGFP protein (A), accumulation of Snq2-yEGFP in aberrant ER structures (B), and induction of the UPR response (C, GFP-Snc1-PEM is shown for comparison).",
    "ncbi_link": "PEM: 
Snq2: 851574
ypt1-1: 850505"
  },
  {
    "caption": "D-F. Synergistic effect of co-overexpression of Snq2-GFP with DsRed-Snc1-PEM in atg11∆ mutant cells. WT (left) and atg11∆ mutant cells (right) were transformed with plasmids for overexpression of Snq2, Snc1-PEM or both Snq2 and Snc1-PEM. D. Immunoblot analysis and quantification. Shown from top to bottom: Snq2-yEGFP (using anti-GFP antibodies), Ds-Red-Snc1-PEM (using anti-Snc1 antibodies), G6PDH (loading control), and a bar graph showing fold increase of Snq2-yEGFP (green) and Ds-Red-Snc1-PEM (red) in atg11∆ mutant cells over WT.",
    "ncbi_link": "atg11: 856162
Snc1: 851203
Snq2: 851574"
  },
  {
    "caption": "E. Accumulation of macro-ER-phagy cargos in aberrant intracellular structures using live-cells microscopy. Shown from left to right: DIC, GFP, DsRed and Merge. Shown from top to bottom: Snq2, Snc1-PEM, Snq2+Snc1-PEM, and % cells with co-localization (relevant only for co-overexpression) (% cells with ER-phagy cargo accumulation in aberrant intracellular structures is shown in S5A Fig). F. Fluorescence level of intracellular structures (ratio over PM) in atg11∆ mutant cells. The bar graph shows Snq2-yEGFP (green) and Ds-Red-Snc1-PEM (red) fluorescence (20 cells were analyzed for each strain). When co-overexpressed in atg11∆ mutant cells, the fluorescence level of either protein accumulating in aberrant structures is ~5 fold higher than when overexpressed individually. +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "atg11: 856162
Snc1: 851203
Snq2: 851574"
  },
  {
    "caption": "A. A diagram showing two groups of ER-resident proteins: those that become macro-ER-phagy cargos (in green), and those that do not (in blue or grey). Like overexpressed Snc1-PEM or Snq2, the ER-resident membrane proteins Sec61 (translocon subunit) and Hmg1 (sterol biogenesis) are transported to the vacuole via macro-ER-phagy. In contrast, the ER-to-Golgi exit regulators Sec12 and Sec13 and the ER lumen chaperone Kar2 are not co-transported to the lysosome through macro-ER-phagy. Four or six different strains were used for this analysis: WT (YPT1), pep4∆, and pep4 prb1∆, ypt1-1, ypt1-1pep4∆, and ypt1-1pep4∆ prb1∆. In each strain, one ER-resident protein was tagged at its C-terminus (except for Kar2). (The pep4∆ strains were not used in all experiments because they do not show the full defect). The level of ER-resident proteins was determined by immunoblot analysis in cells that either do not (B-D) or do overexpress GFP-Snc1-PEM (F-H). B-C. Sec61-3xHA (B) and Sec13-3x HA (C) expressing cells (2 independent un-transformed colonies) were tested by immunoblot analysis (using anti-HA antibodies). Shown from top to bottom: strain genotype, HA-tagged protein, G6PDH (loading control), quantification of HA-tagged protein expressed as average fold of WT (p-value = 0.025 for Sec61).",
    "ncbi_link": "pep4: 855949
prb1: 856649
ypt1-1: 850505"
  },
  {
    "caption": "D. Summary of immunoblot analyses of ER-resident proteins level in cells that do not overexpress GFP-Snc1-PEM: WT (PEP4PRB1) vs pep4∆ prb1∆ (left), ypt1-1PEP4PRB1 vs ypt1-1pep4∆ prb1∆ (right). Immunoblots and quantification are shown in Fig 6B-6C and S6A-S6C Fig. In YPT1 cells, the levels of Sec61 and Hmg1 (green) are slightly increased (14 and 38%, respectively) in strains defective in vacuolar proteolysis; the levels of Sec12, Sec13 and Kar2 are not increased (blue and grey). The levels of Sec61 and Hmg1 (green) are increased by 2-2.5 fold in ypt1-1 mutant cells when compared to WT cells, regardless if they are defective in vacuolar proteolysis or not. In contrast, the levels of Sec12, Sec13 and Kar2 are only slightly increased (blue and grey).",
    "ncbi_link": "PEP4: 855949
pep4: 855949
PRB1: 856649
prb1: 856649
YPT1: 850505
ypt1-1: 850505"
  },
  {
    "caption": "E. The level of the ER-resident protein Sec61 is similar whether GFP-Snc1-PEM is overexpressed or not. Wild-type cells were transformed with a 2μ plasmid, either empty or for overexpression of GFP-Snc1-GEM (2 independent transformants). Shown from top to bottom: plasmid, Sec61, G6PDH (loading control), GFP-Snc1-PEM, and quantification of Sec61 expressed as average fold of WT with empty plasmid.",
    "ncbi_link": "Snc1: 851203"
  },
  {
    "caption": "H. Summary of immunoblot analysis of ER-resident proteins level in cells overexpressing GFP-Snc1-PEM: WT (PEP4PRB1) vs pep4∆ prb1∆ (left), ypt1-1PEP4PRB1 vs ypt1-1pep4∆ prb1∆ (right). Immunoblots and quantification are shown in Fig 6F and 6G and S6F-S6H Fig. In YPT1 cells, like Snc1-PEM (black), the levels of Hmg1 and Sec61 (green) are increased >10 fold in strains defective in vacuolar proteolysis. In contrast, the levels of Sec12, Sec13 and Kar2 are not changed (blue and grey). Like Snc1-PEM (black), the protein levels of Hmg1 and Sec61 (green) are increased ~15 fold in ypt1-1 mutant cells when compared to WT cells, regardless if they are defective in vacuolar proteolysis or not. In contrast, the levels of Sec12, Sec13 and Kar2 are only slightly increased (blue and grey). +/- and error bars represent STDEV. Results in this figure represent at least two independent experiments.",
    "ncbi_link": "PEP4: 855949
pep4: 855949
PRB1: 856649
prb1: 856649
YPT1: 850505
ypt1-1: 850505"
  },
  {
    "caption": "A. In cells defective in vacuolar proteolysis (pep4∆ prb1∆), Hmg1 co-localizes with 70% of intra-cellular Snc1-PEM, but Sec13 does not (at least 36 cells were analyzed for each strain). No co-localization was observed for resident ER proteins and overexpressed Snc1-PEM in WT cells (PEP4PRB1). Hmg1 (left) and Sec13 (right) were tagged with mCherry at their C-terminus in PEP4PRB1 (WT) and pepb4∆ prb1∆ mutant cells. Cells were transformed with a 2μ plasmid for overexpression of GFP-Snc1-PEM and analyzed by live-cell microscopy. Shown from top to bottom: DIC, GFP, mCherry, merge (yellow), % cells with intra-cellular Snc1-PEM, and % co-localization of the ER protein with intra-cellular Snc1-PEM.",
    "ncbi_link": "pep4: 855949
PEP4: 855949
prb1: 856649
PRB1: 856649"
  },
  {
    "caption": "B. The ER-resident protein Hmg1 is delivered to the vacuole with GFP-Snc1-PEM. The vacuole of PEP4PRB1 (WT) and pepb4∆ prb1∆ mutant cells expressing Hmg1-mCherry and overexpressing GFP-Snc1-PEM (see Panel A, left) was stained with CMAC-Arg (blue), and the cells were analyzed by live-cell microscopy. In WT cells (top), there is no intracellular Snc1-PEM and the red-labeled ER is distinguished from the blue vacuole. In contrast, in ~75% pep4∆ prb1∆ mutant cells (bottom), which are defective in vacuolar proteolysis, Hmg1 (red) co-localizes with Snc1-PEM (green) in the vacuole (blue). Shown from left to right: DIC, GFP, mCherry, blue, merge (white shows merge of the three colors), % cells with intracellular Snc1-PEM, % cells in which Hmg1 with Snc1-PEM co-localize, and % co-localization of the two proteins with the vacuolar dye (38 cells were analyzed for each strain).",
    "ncbi_link": "PEP4: 855949
pep4: 855949
PRB1: 856649
prb1: 856649"
  },
  {
    "caption": "C. >80% of ypt1-1 mutant cells, regardless if they are PEP4PRB1 or pep4∆ prb1∆, accumulate aberrant GFP-Snc1-PEM structures. Hmg1 co-localizes with >70% of these structures, whereas Sec13 co-localizes with only ~15% of these structures (36-43 cells were analyzed for each strain). The experiment was done as described for Panel A.",
    "ncbi_link": "PEP4: 855949
pep4: 855949
PRB1: 856649
prb1: 856649
ypt1: 850505"
  },
  {
    "caption": "D. Summary of microscopy analysis of ER-resident proteins co-localization with GFP-Snc1-PEM in cells overexpressing GFP-Snc1-PEM: WT (PEP4PRB1) vs pep4Δ prb1Δ (left), and ypt1-1PEP4PRB1 vs ypt1-1pep4Δ prb1Δ (right). Microscopy and quantification are shown in Fig 7A and 7C and S7 Fig. In YPT1 cells, whereas >60% of Hmg1 and Sec61 (green) co-localize with Snc1-PEM in strains defective in vacuolar proteolysis, Sec12, Sec13 and Kar2 are not changed significantly (blue and grey). Hmg1 and Sec61 (green) co-localize with Snc1-PEM in >70% of ypt1-1 and >80% of ypt1-1pep4Δ prb1Δ mutant cells, whereas Sec13 and Kar2 (blue and grey) do so in <15% of the cells. The level of Sec12 co-localization with Snc1-PEM is intermediate, ~38% in ypt1-1 and ypt1-1pep4Δ prb1Δ. Error bars represent STDEV. Results in panels A and B represent at least two independent experiments.",
    "ncbi_link": "PEP4: 855949
pep4: 855949
PRB1: 856649
prb1: 856649
ypt1: 850505
YPT1: 850505"
  },
  {
    "caption": "(C) We modelled serum NfL levels (log-transformed) in SCA3 carriers (n=123) with the predictors age and ATXN3 CAG repeat length, their squares and all possible interactions (for details, see Results and Methods). The highly significant predictors (age, its square, and repeat length, and the intercept, all p<.001, explained variance: R2=0.37) were used to generate the diagram. For a given age, each increase in CAG repeat count was associated with higher NfL concentrations. The steepness of the slopes declined with increasing age. In controls (black, n=125), the relation between NfL level (log-transformed) and age was linear.",
    "ncbi_link": "ATXN3: 4287"
  },
  {
    "caption": "(A) In vitro Methyltransferase activity. Recombinant proteins Nsp10  and Nsp16  wt or Nsp16mut were combined with cap0   RNA and Adenosyl-L-methionine ([methyl-3H] SAM) for 90 min at 37°C. Methylation  of cap0   RNA was quantified using a scintillation counter  (Beckmann).(-) control did not contain any recombinant protein. Results are plotted as mean of triplicate reactions with error bars representing SD. One out of three independent biological repeats is shown. Data information: Statistical analysis was done using a one-way ANOVA followed by Tukey's multiple comparisons test.",
    "ncbi_link": "cap0: "
  },
  {
    "caption": "(A) Calu-3  cells were incubated with the indicated amounts of  type I IFN  24 h prior to infection  with normalized amounts of SARS-CoV-2  wt (WT) or  Nsp16mut at 0.015 RNA copies/cell. Viral load  in the supernatant was quantified at the indicated time points by RT-qPCR  targeting viral polymerase RdRp. Results are plotted as mean of triplicate infections  with error bars representing the SD (biological replicates). One out of three independent experiments is shown (n=3). Three days postinfection,  protein expression of IFIT1  was analyzed by immunoblot  to control for  type I IFN treatment. Membranes  were probed with antibodies targeting IFIT1  and the housekeeping gene HSP90. Data information: Statistical analysis was done using two-way ANOVA followed by Bonferroni's multiple comparisons test. ns = not significant (p>0.05).",
    "ncbi_link": "Nsp16: 43740578
RdRp: 43740578"
  },
  {
    "caption": "(C)  Calu-3 cells lacking MDA5  (MDA5  KO), RIG-I  (RIG-I KO), or control KO cells (Ctrl) were seeded into 96well plates and infected with increasing amounts of SARS-CoV-2 wt (WT) or Nsp16mut in triplicates (biological replicates). Type I IFN release was quantified after 48 h by incubating supernatants with HEK-Blue IFN-α/β reporter cells. SEAP activity in the supernatant of the reporter cells is shown as mean of quadruplicates with error bars representing SD. (D) Calu-3 cells (Ctrl) were seeded into 96 well plates and infected with 10 RNA copies/cell of SARS-CoV-2 wt (WT) or Nsp16mut in the presence of increasing amounts of Remdesivir  (RDV). Type I IFN release was quantified after 48 h by IFN bioassay  on  HEK-Blue IFN-α/β and is depicted as mean of quadruplicates with error bars representing SD. In parallel, infectivity  of SARS-CoV-2  wt and Nsp16 in the presence of increasing amounts of RDV  was determined at the indicated time points by RT-qPCR targeting viral polymerase RdRp   transcripts. Data information: Statistical analysis was performed using two-way ANOVA followed by Bonferroni's multiple comparisons test. ns = not significant (p>0.05).",
    "ncbi_link": "MDA5: 64135
Nsp16: 43740578
RdRp: 43740578
RIG-I: 23586"
  },
  {
    "caption": "(B) Three days after SARS-CoV-2 Nsp16mut infection of A549  cells described in (A), expression of IFIT1  and viral nucleocapsid protein N was analyzed by immunoblot. Membranes  were probed with antibodies targeting IFIT1, SARS-CoV-2 N protein, and the housekeeping gene HSP90.",
    "ncbi_link": "Nsp16: 43740578"
  },
  {
    "caption": "(D) IFIT1  expression levels in Calu-3  Ctrl, IFIT1  KO #1 and #2 lines treated with  type I IFN (24 h; 100 U/ml) were analyzed by immunoblot. Membranes  were probed with antibodies targeting IFIT1  or the housekeeping gene HSP90.",
    "ncbi_link": "IFIT1: 3434"
  },
  {
    "caption": "(H) IFIT1  expression was analyzed in mock treated, SARS-CoV-2 wt (WT) or Nsp16mut infected cells at 48 hpi by immunoblot. Membranes  were probed with antibodies targeting IFIT1  and the housekeeping gene HSP90.",
    "ncbi_link": "Nsp16: 43740578"
  },
  {
    "caption": "I, CheY interacts with FliM∆N and this interaction is sensitive to chemotactic stimuli. Each curve is the mean of two FRET measurements of cells in response to an attractant stimulus (0.1 mM serine; in the case of FliMwt, a single measurement was performed with serine; another measurement of FliMwt with 1mM aspartate produced similar results). FRET ratio is the ratio of mCherry to YPet fluorescence. CheY-mCherry and mCherry concentrations were ~170 µM in the case of FliM∆N and ~15 µM in the case of FliMwt Strains used: EW677 (FliMwt, red), EW659 (negative control of FliM∆N without CheY, purple), EW637 (FliM∆N, blue), and EW636 (FliM∆N ∆cheA, yellow).",
    "ncbi_link": "cheA: 946401
FliM: 946442"
  },
  {
    "caption": "C, The response of tethered fliM∆N ΔcheZ cells (strain EW635), induced for CheY expression from a plasmid (200 µM IPTG), to positive stimuli. Lines and shaded regions are the mean time spent in clockwise rotation ± SEM. The arrow marks the estimated time at which the stimulant arrived to, or left (as indicated), the flow chamber. N is the number of cells. α-Methyl-DL-aspartate (MeAsp) and leucine were used at 1 mM, benzoate (pH 7.0) at 50 mM.",
    "ncbi_link": "cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "The response of tethered fliM∆N ΔcheZ cells (strain EW635), induced for CheY expression from a plasmid (200 µM IPTG) Lines and shaded regions are the mean time spent in clockwise rotation ± SEM. The arrow marks the estimated time at which the stimulant arrived to, or left (as indicated), the flow chamber. N is the number of cells. α-Methyl-DL-aspartate (MeAsp) and leucine were used at 1 mM, benzoate (pH 7.0) at 50 mM. D, negative stimuli.",
    "ncbi_link": "cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "E, Response of tethered fliM∆N ΔcheA cells (strain EW634) to acetate (50 mM, pH 7.0) at different CheY concentrations. Lines and shaded regions are mean ± SEM.",
    "ncbi_link": "cheA: 946401
fliM: 946442"
  },
  {
    "caption": "F, Response of tethered fliM∆N ΔcheZ cells (strain EW635) to acetate.",
    "ncbi_link": "cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "G, Contribution of acetylation and phosphorylation of CheY as well as its D13K mutation to clockwise rotation. The points are the mean clockwise rotation at time segments 0-20 s and 160-180 s. The variants shown are fliM∆N ∆cheZ cells expressing CheY in the absence of presence of acetate (10 mM, pH 7.0) (i.e., CheY~P and CheY~P~Ac; blue and green curves; strain EW635), fliM∆N ∆cheA cells expressing CheY, in the absence of presence of acetate (CheY and CheY~Ac; purple and red, respectively; EW634), and fliM∆N ∆cheA cells expressing CheY(D13K) (burgundy; EW737). Each data point is the average of all experiments at a given CheY concentration, weighted by the sample number of each experiment. The CheY concentrations shown are estimates based on the calibration curves for which a similar CheY expression system was used.",
    "ncbi_link": "cheA: 946401
cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "H, FliMN further activates CheY variants to produce clockwise rotation. The variants shown are fliM∆N ∆cheZ cells expressing FliMN-CheY (i.e., FliMN-CheY~P; blue curve; strain EW697), fliM∆N ∆cheA cells expressing FliMN-CheY, in the absence of presence of acetate (10 mM, pH 7.0) (FliMN-CheY and FliMN-CheY~Ac; purple and red, respectively; EW696), and fliM∆N ∆cheA cells expressing FliMN-CheY(D13K) (burgundy; EW739).",
    "ncbi_link": "cheA: 946401
cheZ: 946392
fliM: 946442"
  },
  {
    "caption": " I, Response of fliM∆N ∆cheA cells expressing FliMN-CheY (strain EW696) to acetate and benzoate (10 mM each; pH 7.0). FliMN-CheY expression was induced with 800 μM IPTG. Lines and shaded regions are the mean time spent in clockwise rotation ± SEM. The black arrow indicates the estimated time point at which the stimulus entered the flow chamber. ",
    "ncbi_link": "cheA: 946401
fliM: 946442"
  },
  {
    "caption": ", Dependence of clockwise rotation on the level of FliMN-CheY~Ac. The red and purple curves are two experimental days in which the clockwise production by fliM∆N ∆cheA cells expressing FliMN-CheY was measured as a function of FliMN-CheY concentration (strain EW696; Concentrations are estimates based on the calibration curves or which a similar CheY expression system was used. ach data point is a mean ± SEM of the data or the second and third experimental days of this strain (in the presence of acetate).",
    "ncbi_link": "cheA: 946401
fliM: 946442"
  },
  {
    "caption": "A, Effects of FliMN-CheY acetylation and phosphorylation on clockwise rotation of tethered cells containing FliM∆N FliN(A93D) motors. Acetate concentration was 10 mM each (pH 7.0). FliMN-CheY and FliMN-CheY~P were produced by using ∆cheA and ∆cheZ backgrounds (strains EW713 and EW714), respectively. Each data point is the average of all measurements at a given FliMN-CheY concentration, weighted by the sample number of each experiment. The concentrations shown are estimates based on the calibration curves for which a similar CheY expression system was used. Concentrations larger than 500 μM were calculated by the linear extrapolation of the calibration curve. B, Distribution of clockwise interval lengths at different average clockwise levels in ∆cheA cells containing FliM∆N FliN(A93D) motors and expressing FliMN-CheY (strain EW713), in the presence of acetate (10 mM, pH 7.0). C, Average clockwise interval length, calculated as the inverse of the rate constants from mono-phasic fits of the distributions in (B).",
    "ncbi_link": "cheA: 946401
cheZ: 946392
FliM: 946442
FliN: 946423"
  },
  {
    "caption": "D, Response of tethered ∆cheZ cells having FliM∆N FliN(A93D) motors to acetate addition and removal (red; strain EW714; FliMN-CheY concentration estimated at ~300 μM). Similar results were obtained with a ∆cheA strain (EW713). Tethered cells having FliM∆N FliNwt motors and containing FliMN-CheY (strain EW696) are shown Acetate concentration was 10 mM (pH 7.0). The data shown are the mean ± SEM. N is the number of cells. Black lines indicate the clockwise-decay rates of FliNwt motors' slow phase and of FliN(A93D) motors following acetate removal.",
    "ncbi_link": "cheA: 946401
cheZ: 946392
FliM: 946442
FliN: 946423"
  },
  {
    "caption": "A, CheY crosslinks with FliM∆N-YPet in vivo. The cytoplasm of fliM∆N-YPet ΔcheZ cells overexpressing CheY (strain EW694) or FliMN-CheY (strain EW697) from a plasmid was crosslinked by glutaraldehyde and resolved by SDS-PAGE. 1, 2, 3 stand for three different experiments that underwent this procedure. The plus sign before ~14 and ~15 stands for +55 kDa of FliM∆N-YPet. Note that gel running suffered from parabolic distortion in band positions. The annotations relate to the lowest positions of the bands. The gel was imaged for FliM∆N-YPet fluorescence. To see the crosslinking products, the intense fluorescence of monomeric FliM∆N-YPet is shown at saturation.",
    "ncbi_link": "YPet: 
cheZ: 946392
FliM: 946442
fliM: 946442"
  },
  {
    "caption": "C, Clockwise rotation of tethered fliM(R94S)∆N ∆cheZ cells and fliM(R94L)∆N ∆cheZ cells expressing FliMN-CheY (strains EW731 and EW733, respectively) in the absence or presence of acetate (10 mM, pH 7.0). FliMN-CheY concentration was estimated to be ~4 mM by extrapolation of the calibration curves for which a similar CheY expression system was used. No clockwise rotation was observed when benzoate substituted for acetate. Each data point is the mean of a separate experiment. Black line is the mean of all experiments.",
    "ncbi_link": "cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "D, Clockwise rotation of tethered fliM(E214W)∆N ΔcheZ cells (strain EW718) at various concentrations of FliMN-CheY. The concentrations shown are estimates based on the calibration curve , for which a similar CheY expression system was used. Each data point is the average of all measurements at similar FliMN-CheY concentrations, weighted by the sample number of each experiment.",
    "ncbi_link": "cheZ: 946392
fliM: 946442"
  },
  {
    "caption": "(C) Equal amounts of WT cells and indicated single or double mutants in serial dilutions were incubated on agar plates at the indicated temperatures. The synthetic growth defects of vps4∆ tul1∆ or vps4∆ ubx3∆ double mutants at 26°C and 37°C were complemented with plasmids encoding VPS4 or TUL1 or UBX3. The dashed boxes indicate the non-complemented double mutants.",
    "ncbi_link": "TUL1: 853832
tul1: 853832
UBX3: 851467
ubx3: 851467
VPS4: 856303
vps4: 856303"
  },
  {
    "caption": "(A) Vacuolar proteolysis-deficient pep4∆ and tul1∆ pep4∆ cells were labeled to saturation with heavy 13C6,15C2-L-lysine and then chased for 3 hours in presence of light L-lysine, following quantitative proteome analysis by LC-MS (two biological replicates). To analyze Dsc complex-dependent protein turnover, the ratio of H/L ratios of tul1∆ pep4∆ over pep4∆ cells of 2511 proteins quantified in both strains was plotted, and proteins with a ratio of H/L ratios >2 were selected. Red squares: regulated proteins with at least one predicted transmembrane (TM) domain; black triangles: regulated proteins without TM domains.",
    "ncbi_link": "pep4: 855949
tul1: 853832"
  },
  {
    "caption": "(B) Epifluorescence and phase contrast microscopy of tul1∆ mutants expressing GFP-Orm2 (green) with Vps4-mCherry (red, endosomes) or with Sec7-mCherry (red, Golgi) or Vps4-eGFP (green) with Sec7-mCherry. Data information: Scale bars = 5 µm.",
    "ncbi_link": "tul1: 853832"
  },
  {
    "caption": "WT cells and the indicated mutants were left untreated (0 min) or were treated with cycloheximide (CHX) to block protein synthesis for 90 min and 180 min at 26°C or at non-permissive temperature (37°C) where indicated. Total cell lysates were analyzed by SDS-PAGE and Western blotting with the indicated antibodies. (C) SEC13 WT and sec13-4 cells were preincubated for 30 minutes at 37°C before CHX was added.",
    "ncbi_link": "SEC13: 850905
sec13: 850905"
  },
  {
    "caption": "(D) Epifluorescence and phase contrast microscopy of living WT cells and cdc48-3 mutants expressing GFP-Orm2 incubated for 5h at the non-permissive temperature (37°C). Data information: Scale bars 5µm.",
    "ncbi_link": "cdc48: 851431"
  },
  {
    "caption": "(E) Epifluorescence and phase contrast microscopy of living tul1∆ and tul1∆ sec13-4 mutants expressing GFP-Orm2 (green) and dsRed-HDEL (red) incubated at 26°C or shifted for 90 minutes to the non-permissive temperature (37°C). Data information: Scale bars 5µm.",
    "ncbi_link": "sec13: 850905
tul1: 853832"
  },
  {
    "caption": "(A) WT (pdr5∆) cells expressing FLAG-Orm2 and Sec61-GFP (integral ER membrane protein) treated with MG-132 were fractionated into insoluble membrane (P100) and soluble cytoplasmic (S100) fractions and analyzed by SDS-PAGE and Western blot with the indicated antibodies.",
    "ncbi_link": "pdr5: 854324"
  },
  {
    "caption": "WT cells, tul1∆ mutants (all in a pdr5∆ strain background) were left untreated or treated with the proteasome inhibitor (MG-132) as indicated and subsequently subjected to subcellular fractionation S100 and P100 fractions were subjected to denaturing FLAG-Orm2 immunoprecipitations (IP). Input and eluted fractions (with FLAG peptide) were analyzed by SDS-PAGE and Western blotting with the indicated antibodies.",
    "ncbi_link": "pdr5: 854324
tul1: 853832"
  },
  {
    "caption": "WT cells and cdc48-3 mutants (all in a pdr5∆ strain background) were left untreated or treated with the proteasome inhibitor (MG-132) as indicated and subsequently subjected to subcellular fractionation S100 and P100 fractions were subjected to denaturing FLAG-Orm2 immunoprecipitations (IP). Input and eluted fractions (with FLAG peptide) were analyzed by SDS-PAGE and Western blotting with the indicated antibodies.",
    "ncbi_link": "cdc48: 851431
pdr5: 854324"
  },
  {
    "caption": "(D) P100 fractions from MG-132-treated WT (pdr5∆) cells expressing FLAG-Orm2 and Sec61-GFP were extracted with Na2CO3 solution at the indicated pH and subsequently fractionated by 100.000 x g centrifugation into soluble (S) and insoluble membrane (M) fractions, subjected to denaturing FLAG-immunoprecipitations and analyzed by Western blotting with the indicated antibodies. The asterisk indicates reactivity of the secondary antibody with IgG heavy chains.",
    "ncbi_link": "pdr5: 854324"
  },
  {
    "caption": "(A) The levels of two major ceramide (Cer) species in lipid extracts from WT (black), tul1Δ (dark gray) or Orm2-K25,33R mutants (light grey) were measured using LC-MS and quantified using spiked non-yeast ceramides as internal standard. Data are normalized to Cer44:0;4 levels of WT cells (set to 1) and presented as mean ±standard deviation from three independent experiments. Pairwise statistical significance was assessed by Student's t-test. p values are given above the respective bars.",
    "ncbi_link": "Orm2: 851064
tul1: 853832"
  },
  {
    "caption": "(B) Autoradiogram of sphingolipid extracts from [3H]serine radiolabelled WT cells and tul1∆ mutants were separated by thin layer chromatography. IPC, Inositolphosphorylceramide; MIPC, mannosylinositolphosphorylceramide; MIP2C, mannosyldiinositolphosphorylceramide. X indicates an unknown lipid species that is insensitive to myriocin treatment.",
    "ncbi_link": "tul1: 853832"
  },
  {
    "caption": "(C) SDS-PAGE and Western blot analysis with the indicated antibodies of input and elution (with FLAG peptide) from native anti-FLAG co-immunoprecipitations from cells expressing FLAG-Orm2-WT or FLAG-Orm2-K25,33R. Control cells expressed untagged Orm2 WT. The asterisks label unspecific cross-reactions of the respective antibodies.",
    "ncbi_link": "FLAG: 
Orm2: 851064"
  },
  {
    "caption": "SDS-PAGE or Phos-tag-PAGE and Western blot analysis with the indicated antibodies of total cell lysates (D) from WT cells expressing FLAG-Orm2 or FLAG-Orm2-K25,33R The asterisks label unspecific cross-reactions of the respective antibodies.",
    "ncbi_link": "FLAG: 
Orm2: 851064"
  },
  {
    "caption": "SDS-PAGE or Phos-tag-PAGE and Western blot analysis with the indicated antibodies of total cell lysates (E) from WT cells and tul1∆ mutants expressing FLAG-Orm2, FLAG-Orm2-3A or FLAG-Orm2-3D with or without Myriocin treatment (1.5 µM) for one hour.",
    "ncbi_link": "FLAG: 
Orm2: 851064
tul1: 853832"
  },
  {
    "caption": "(A) Left panel: In tor1-1 avo3∆1274-1430 cells rapamycin specifically inhibits TORC2 but not TORC1 (Gaubitz et al., 2015). tor1-1 avo3∆1274-1430 cells were treated with cycloheximide (CHX) and rapamycin or vehicle (methanol) for the indicated times. Right panel: WT or Orm2 mutant cells were treated with CHX for the indicated times. The protein levels of FLAG-Orm2 or of the indicated FLAG-Orm2 mutants from total cell lysates were analyzed by SDS-PAGE and Western blotting with the indicated antibodies.",
    "ncbi_link": "Orm2: 851064
tor1: 853529
avo3: 856828"
  },
  {
    "caption": "(C) Denaturing immunoprecipitation (IP) of FLAG-Orm2, FLAG-Orm2-3A and FLAG-Orm2-3D. The control strain expresses untagged Orm2. Input and elutions (with FLAG peptides) were analyzed by SDS-PAGE and Western blot with the indicated antibodies.",
    "ncbi_link": "FLAG: 
Orm2: 851064"
  },
  {
    "caption": "(D) Epifluorescence and phase contrast microscopy of living tul1∆ mutants expressing GFP-Orm2, GFP-Orm2-3A or GFP-Orm2-3D (green) with dsRed-HDEL (red). Arrowheads point to GFP-Orm2 accumulations outside the endoplasmic reticulum (ER). Scale bars = 5 µm.",
    "ncbi_link": "tul1: 853832"
  },
  {
    "caption": "(E) SDS-PAGE and Western blot analysis with the indicated antibodies of input and elution (with FLAG peptide) from native anti-FLAG co-immunoprecipitations from cells expressing FLAG-Orm2-K25,33R, FLAG-Orm2-K25,33R-3A or FLAG-Orm2-K25,33R-3D. The control strain expresses untagged Orm2.",
    "ncbi_link": "FLAG: 
Orm2: 851064"
  },
  {
    "caption": "(F) The levels of the long chain bases (LCB) C18-dihydrosphingosine (C18-DHS) and C18-phytosphingosine (C18-PHS) and of two major ceramide (Cer) species in lipid extracts from WT, tul1∆, Orm2-K25,33R, Orm2-3A and Orm2-3D mutants were measured using LC-MS and quantified using spiked non-yeast LCBs/ceramides as internal standard. Data are normalized to WT levels of the most abundant LCB/ceramide species (set to 1) and presented as mean ±standard deviation from three independent experiments. Pairwise statistical significance was assessed by Student's t-test. p values are given above the respective bars.",
    "ncbi_link": "Orm2: 851064
tul1: 853832"
  },
  {
    "caption": "(C) Bar plots showing mean mRNA levels of vascular cell adhesion molecule-1 (VCAM1), intracellular adhesion molecule-1 (ICAM1), and E-selectin (SELE), measured 4 hrs after stimulation of human ECs with or without TNF-α ± miR-3679-5p. Data are shown as means ± SE (n=3). *P < 0.05 compared to TNF-α (-) mimics (-). † P < 0.05 and ‡ P = 0.203 compared to TNF-α (+) mimics (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "ICAM1: 3383
intracellular adhesion molecule-1: 3383
miR-3679-5p: 100500878
E-selectin: 6401
SELE: 6401
vascular cell adhesion molecule-1: 7412
VCAM1: 7412"
  },
  {
    "caption": "(D) Western blots for VCAM1, ICAM, SELE, and β-actin (ACTB) in lysates from ECs treated with or without TNF-α (4 hrs) ± miR-3679-5p.",
    "ncbi_link": "miR-3679-5p: 100500878"
  },
  {
    "caption": "(E) Representative images (top) and bar plot quantification (bottom) showing the adhesion of calcein-labeled U937 monocytes to ECs treated with or without TNF-α ± miR-3679-5p. Scale bar represents 250 μm. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-) mimics (-). † P < 0.05 compared to TNF-α (+) mimics (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "miR-3679-5p: 100500878"
  },
  {
    "caption": "(F) The scatter plot shows the correlation of RNA immunoprecipitation (RIP)　followed by microarray data from two replicate screens for the identification of miR-3679-5p target genes. Genes up- and down-regulated by miR-3679-5p treatment (|average Log2FC|>1) are indicated in red and blue, respectively.",
    "ncbi_link": "miR-3679-5p: 100500878"
  },
  {
    "caption": "(J and K) Effect of miR-3679-5p mimics (J) or miR-3679-5p inhibitor (K) on luciferase activity in pmirGLO-transfected ECs expressing the 3′ UTR of KDM7A. Data are shown as means ± SE (n=3). *P < 0.05 compared to control. Statistical differences were analyzed by the Student's t test.",
    "ncbi_link": "KDM7A: 80853
miR-3679-5p: 100500878"
  },
  {
    "caption": "(M and N) The effect of miR-3679-5p mimics (M) or miR-3679-5p inhibitor (N) on luciferase activity in pmirGLO-transfected ECs expressing the 3′ UTR of UTX was measured. Data are shown as means ± SE (n=3). *P < 0.05 compared to control. Statistical differences were analyzed by the Student's t test.",
    "ncbi_link": "UTX: 7403
miR-3679-5p: 100500878"
  },
  {
    "caption": "(A) Heat map representation of RNA-seq results. The p65-dependent genes (total 123; defined as genes up-regulated more than 2-fold via TNF-α treatment and down-regulated more than 0.75-fold via BAY 11-7082 treatment) were classified based on the alteration patterns by the siRNA knockdown of KDM7A, UTX, and both, using the algorithm \"HOPACH\".",
    "ncbi_link": "UTX: 7403
KDM7A: 80853"
  },
  {
    "caption": "(C-E) Bar plot showing mean mRNA levels of VCAM1, ICAM1, and SELE measured 4 hrs after stimulation of ECs with or without TNF-α ± (siKDM7A+siUTX). Data are shown as means ± SE (n=3). *P < 0.05 compared to TNF-α (-) siKDM7A+siUTX (-). † P < 0.05 compared to TNF-α (+) siKDM7A+siUTX (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "ICAM1: 3383
UTX: 7403
KDM7A: 80853
SELE: 6401
VCAM1: 7412"
  },
  {
    "caption": "(F) Western blots for VCAM1, ICAM, SELE, and ACTB in lysates from ECs treated with or without TNF-α (4 hrs) ± (siKDM7A+siUTX).",
    "ncbi_link": "UTX: 7403
KDM7A: 80853"
  },
  {
    "caption": "(G) Representative images (top) and bar plot quantification (bottom) showing the adhesion of calcein-labeled U937 monocytes to ECs treated with or without TNF-α ± (siKDM7A+siUTX). Scale bar represents 250 μm. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-) siKDM7A+siUTX (-). † P < 0.05 compared to TNF-α (+) siKDM7A+siUTX (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "UTX: 7403
KDM7A: 80853"
  },
  {
    "caption": "(G and H) Gene tracks of ChIP-seq signals for H3K27Ac, p65, KDM7A, and UTX, and RNA-seq signals around the VCAM1 (G) and SELE (H) loci in TNF-α (-) and TNF-α (+) ECs. ChIP-Seq and RNA-seq signals are visualized by Integrated Genome Viewer (http://software.broadinstitute.org/software/igv/).",
    "ncbi_link": "SELE: 6401
VCAM1: 7412"
  },
  {
    "caption": "(I and J) ChIP-qPCR of p65 (I) and KDM7A (J) at the VCAM1 TSS, normalized to input. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). † P < 0.05 compared to TNF-α (+) siKDM7A (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "KDM7A: 80853
VCAM1: 7412"
  },
  {
    "caption": "(K and L) ChIP-qPCR of p65 (K) and UTX (L) at the SELE TSS, normalized to input. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "SELE: 6401"
  },
  {
    "caption": "(C) Gene tracks of ChIP-seq signals for H3K9me2 and H3K27me3 around the VCAM1 locus in TNF-α (-) and TNF-α (+) ECs.",
    "ncbi_link": "VCAM1: 7412"
  },
  {
    "caption": "(D and E) ChIP-qPCR showing enrichment (percent input) of H3K9me2 (D) and H3K27me3 (E) around the VCAM1 locus. Primer pairs targeting distinct regions are listed on the X axis. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). Statistical differences were analyzed by the Student's t test.",
    "ncbi_link": "VCAM1: 7412"
  },
  {
    "caption": "(F) Gene tracks of ChIP-seq signals for H3K9me2 and H3K27me3 around the SELE locus in TNF-α (-) and TNF-α (+) ECs.",
    "ncbi_link": "SELE: 6401"
  },
  {
    "caption": "(G and H) ChIP-qPCR showing enrichment (percent input) of H3K9me2 (G) and H3K27me3 (H) around the SELE locus. Primer pairs targeting distinct regions are listed on the X axis. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). Statistical differences were analyzed by the Student's t test.",
    "ncbi_link": "SELE: 6401"
  },
  {
    "caption": "(I and J) ChIP-qPCR showing enrichment (percent input) of H3K9me2 and H3K27me3 around the HOXA13 (I) and GATA4 (J) loci. Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). Statistical differences were analyzed by the Student's t test.",
    "ncbi_link": "GATA4: 2626
HOXA13: 3209"
  },
  {
    "caption": "(K and L) ChIP-qPCR showing enrichment (percent input) of H3K9me2 around VCAM1 -11kb (K) and H3K27me3 around SELE -12kb (L). Graphs are representative of three independent experiments. Data are shown as means ± SD. *P < 0.05 compared to TNF-α (-). † P < 0.05 compared to TNF-α (+) siKDM7A (-) or TNF-α (+) siUTX (-). Statistical differences were analyzed by the Tukey-Kramer test.",
    "ncbi_link": "UTX: 7403
KDM7A: 80853
SELE: 6401
VCAM1: 7412"
  },
  {
    "caption": "(G and H) ChIA-PET interactions of active RNA pol II around the VCAM1 (G) and IL8 (H) loci integrated with the ChIP-seq profiles of KDM7A, UTX, and BRD4, and RNA-seq profiles in TNF-α (-) and TNF-α (+) ECs. ChIA-PET interactions were visualized by the WashU Epigenome Browser (http://epigenomegateway.wustl.edu/browser/). Interactions detected by ChIA-PET are depicted with purple lines. Red bars show TNF-α-specific SEs.",
    "ncbi_link": "IL8: 3576
VCAM1: 7412"
  },
  {
    "caption": "(I-K) Gene tracks of ChIP-seq signals for H3K9me2 and H3K27me3 around VCAM1 (I), IL8 (J), and SELE (K) in TNF-α (-) and TNF-α (+) ECs. Red bars show TNF-α-specific SEs.",
    "ncbi_link": "IL8: 3576
SELE: 6401
VCAM1: 7412"
  },
  {
    "caption": "(A-D) BMDMs treated with cytochalasin D were infected with aggregates of different Mtb strains and imaged by time-lapse microscopy at 1-hour intervals for 60 hours. The plots represent the percentage of macrophages that die within the first 12 hours after stable contact with an Mtb aggregate. Each symbol represents the percentage of dead macrophages for a single biological replicate (n ≥ 3 replicates with ≥ 70 cells per replicate). Bars represent means and standard deviations. P-values were calculated using a one-way ANOVA test (A,C,D) or t test (B) comparing each strain to the wild-type reference strain (A-D); ns, P values > 0.05. (A) Macrophages in contact with aggregates of Mtb H37Rv wild-type (WT), ∆RD1 mutant and complemented ∆RD1 mutant (∆RD1::2F9). (B) Macrophages in contact with aggregates of Mtb Erdman wild-type (WT) or PDIM-deficient (fadD26) strains. (C) Macrophages in contact with aggregates of Mtb Erdman wild-type (WT) or mutant strains (espI eccD1, esxA, espA) and the complemented strains (esxA::esxBA, espA::espA). (D) Macrophages in contact with aggregates of Mtb Erdman wild-type (WT) or mutant strains (espB, espA espB) and the espB-complemented strains (espB::espB, espA espB::espB).",
    "ncbi_link": "eccD1: 886207
espA: 885377
espB: 886214
espI: 886206
esxA: 886209
esxB: 886194
fadD26: 887603
PDIM: 887603"
  },
  {
    "caption": "(C) Expression profile of the indicated ion channel analyzed by RT-PCR in the WM266.4 and 451Lu metastatic melanoma cell lines (middle and bottom panels, respectively). Expected amplicons sizes (positive controls in top panel) are in base pairs (bp); TRPV1=120, TRPV2=199, TRPV3=226, TRPV4=190/370, TRPV6=208, TRPC1=201, TRPC6=121, TRPM2=303, TRPM7=226, TRPA1=140, Orai1=161, STIM1=109, STIM2=114).",
    "ncbi_link": "Orai1: 84876
STIM1: 6786
TRPA1: 8989
TRPC1: 7220
TRPC6: 7225
TRPM2: 7226
TRPM7: 54822
TRPV1: 7442
TRPV2: 51393
TRPV3: 162514
TRPV4: 59341
TRPV6: 55503"
  },
  {
    "caption": "(G) TRPV2 protein expression in melanoma cell lines harboring either B-RAF (black) or N-Ras (blue) mutations. β-Actin was used as a loading control.",
    "ncbi_link": "B-RAF: 673
N-Ras: 4893"
  },
  {
    "caption": "(C) TRPV2 overexpression in the non-invasive 501mel cell line (GFP-TRPV2) or downregulation by lentiviral-delivery of TRPV2 specific shRNAs (shRNA V2-1 and V2-2) in the WM266.4 and 451Lu metastatic melanoma cell lines assessed by western-blot. β-actin was used as a loading control.",
    "ncbi_link": "GFP: 
TRPV2: 51393"
  },
  {
    "caption": "(A) Impact of TRPV2 genetic manipulation in 501mel, WM266.4 and 451Lu on serum-induced migration and matrigel invasion. Representative pictures show crystal violet-stained cells that have migrated through 8 µm pore size membranes. Histograms illustrate the average numbers of migrating/invading cells normalized to control (presented as mean ± SEM of n=3 independent experiments). For 501mel the Mann-Whitney test was used for statistical analysis (**P = 0.0022); For WM266.4&451Lu one-way ANOVA followed by Dunnett's multiple comparisons tests was used (**P < 0.01; ***P < 0.001; ****P < 0.0001 ; See appendix Table S2 for exact P values).",
    "ncbi_link": "TRPV2: 51393"
  },
  {
    "caption": "(D) TRPV2-silencing effect on 3D invasion. Representative images were taken every day for 3 days after collagen embedding of spheroids from WM266.4 cells expressing either shRNA ctrl or TRPV2-targeting shRNAs (scale bar=0.5 mm). (E) Quantification of collagen invasion. For each spheroid, the cell-covered area at day 2 was normalized to the starting area of the collagen-embedded spheroids. Histograms represent the invasion relative to control WM266.4 spheroids (shRNA Ctrl) from at least 12 spheroids from three independent experiments (See also appendix Fig S3C). M. ****P <0.0001 and **P = 0.0012 the Kruskal-Wallis test followed by Dunn's multiple comparisons test.",
    "ncbi_link": "TRPV2: 51393"
  },
  {
    "caption": "(B) Comparison of calpain activity in control (GFP) or overexpressing TRPV2 (GFP-TRPV2) 501mel cells, and in control (shRNA Ctrl) or TRPV2-silenced (shRNA V2-1, -2) WM266.4 cells or 451Lu cells. Bar graphs show mean normalized calpain activity ± SEM (n=3 biological replicates). For 501mel the Mann-Whitney test was used for statistical analysis (*P = 0.05); For WM266.4&451Lu one-way ANOVA followed by Dunnett's multiple comparisons tests was used (**P < 0.01; See appendix Table S2 for exact P values).",
    "ncbi_link": "GFP: 
TRPV2: 51393"
  },
  {
    "caption": "(C) Representative immunoblots showing the full-length (230 kDa ; Black Arrows) and the calpain-mediated degradation product (190 kDa ; Grey Arrows) of talin after overexpression or repression of TRPV2, in the corresponding cell lines. Tubulin was used as a loading control.",
    "ncbi_link": "TRPV2: 51393"
  },
  {
    "caption": "A-D Representative bioluminescence imaging (BLI) data of mice injected intravenously with the non-metastatic melanoma cell line 501mel-Luc transfected with either GFP-TRPV2 or GFP control (A-B), or with the invasive 451Lu-Luc melanoma cell line expressing either control shRNA or TRPV2 targeting shRNA (C-D). Tumor growth and metastasis formation were monitored for 64 days (501mel-Luc) or 35 days (451Lu-Luc) after injection. Graphs presented in A and C show in vivo normalized photon flux quantification at the end time point (ns P = 0.0903 (A) and **P = 0.0064 (C), the Mann-Withney test). Graphs presented in B and D show the number of metastatic foci per animal (B) or per lungs (D) counted at necropsy (*P = 0.0397 (B) and ns P = 0.0691 (D), unpaired t-tests). For (D) Representative ex vivo BLI images of lung metastasis are shown",
    "ncbi_link": "GFP: 
Luc: 
TRPV2: 51393"
  },
  {
    "caption": "(A) TRPV2 RNA expression levels (microarray probe: 219282_s_at) measured in normal skin (n=7 biological replicates), nevi (n=9 biological replicates) , primary (n=31 biological replicates) and metastatic (n=73 biological replicates) melanomas (GEO: GSE46517)(Data ref: Kwong LN, 2013). TRPV2 levels are increased in malignant lesions compared to normal skin and nevi. Data is represented as a whisker-box plot with outliers plotted as individual points (Boxes extend from the 25th to 75th percentiles, whiskers from the 10th to 90th percentiles, the horizontal line in each box is plotted at the median; ns P = 0,1383, *P = 0,0488 and **P = 0,0016, the Kruskal-Wallis test). The horizontal dotted line corresponds to TRPV2 median expression in nevi.",
    "ncbi_link": "TRPV2: 51393"
  },
  {
    "caption": "Survival of age- and sex-matched (8-10 week old) Spata2+/+ (WT) and Spata2-/- (KO) mice injected intraperitoneally (i.p.) with LPS (20 mg/kg bodyweight). Data pooled from three independent experiments are shown. Statistical analysis was performed using long-rank test.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "ELISA of serum IL-1β, IL-18, TNFα and IL-6 at 12 h after injection of WT or Spata2-KO mice with 20 mg/kg LPS. Circles and triangles represent individual mice. Horizontal bars indicate mean values. **P < 0.01; ****P < 0.0001. Statistical analysis was performed using unpaired two-tailed Student's t-test.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Immunoblot analysis of the indicated phosphorylated (P) and total proteins in lysates of LPS-stimulated BMDMs derived from WT or Spata2-KO mice. Molecular weights in kDa are indicated to the right.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "qRT-PCR analysis of the indicated mRNAs in untreated or LPS-stimulated WT or Spata2-KO BMDMs. Bars and error bars represent the mean ± S.D. of triplicate experiments. Statistical analysis was performed using unpaired two-tailed Student's t-test.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "ELISA of TNFα and IL-6 in the supernatants from untreated or LPS-stimulated WT or Spata2-KO BMDMs. Bars and error bars represent the mean ± S.D. of triplicate experiments. Statistical analysis was performed using unpaired two-tailed Student's t-test.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "ELISA of IL-1β secretion by WT or Spata2-KO BMDMs that were either untreated (-) or LPS-primed and then treated with the indicated NLRP3 inducers",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "ELISA of IL-1β secretion by WT or Spata2-KO BMDMs that were either untreated (-) or stimulated with the NLRC4 inducer (Salmonella infection) or AIM2 inducer ( Poly(dA:dT) transfection) (B).",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Immunoblot analysis of the mature IL-1β p17 and the active Caspase-1 p20 in cell supernatants (Sup) and the indicated proteins in the cell extracts (Cell ext) of WT or Spata2-KO BMDMs stimulated as in (A).",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "WT and Spata2 CRISPR knock out (KO) iBMDMs stably expressing GFP-ASC were primed with LPS and stimulated with Nigericin for 1 h. GFP-ASC specks were imaged by confocal microscope, and percentage of ASC speck-positive cells was quantified. Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
ASC: 29108
Spata2: 263876"
  },
  {
    "caption": "BMDMs from Spata2+/+ (WT) and Spata2-/- (KO) mice were pretreated with Caspase-1 inhibitor, Z-YVAD-FMK, for 30 min, primed with LPS, and then stimulated with Nigericin for 1 h. ASC specks were assessed by Immunofluorescence with antibody against ASC and imaged by confocal microscope, and percentage of ASC speck-positive cells was quantified. Scale bar, 10 µm.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Immunoblot analysis of ASC in soluble cell lysate and DSS cross-linked insoluble fraction of WT or Spata2-KO BMDMs primed with LPS and stimulated without or with nigericin (Nig) for 1 h. Relative levels of ASC in cross-linked samples from LPS+ Nig treated cells were quantitated and shown below.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Spata2+/+ (WT) and Spata2-/- (KO) mice were injected intraperitoneally (i.p.) with alum (20 mg/kg bodyweight) and sacrificed 6 h latter to collect peritoneal lavages. Absolute numbers of neutrophils recruited to the peritoneum were counted by FACS (G)",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Spata2+/+ (WT) and Spata2-/- (KO) mice were injected intraperitoneally (i.p.) with alum (20 mg/kg bodyweight) and sacrificed 6 h latter to collect peritoneal lavages. levels of IL-1β (H) and IL-6 (I) in the peritoneal fluids were measured by ELISA.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "ELISA of IL-1β secretion by WT or CYLD KO BMDMs that were either untreated (-) or LPS-primed and then treated with the indicated NLRP3 inducers.",
    "ncbi_link": "CYLD: 74256"
  },
  {
    "caption": "Immunoblot analysis of IL-1β and active caspase-1 p20 in cell supernatants (Sup) and the indicated proteins in cell extracts (Cell ext) from WT and CYLD KO BMDMs, stimulated as in (A).",
    "ncbi_link": "CYLD: 74256"
  },
  {
    "caption": "BMDMs from WT and CYLD KO mice were pretreated with Caspase-1 inhibitor, Z-YVAD-FMK, for 30 min, primed with LPS, and then stimulated with Nigericin for 30 min. ASC specks were assessed by Immunofluorescence with antibody against ASC and the percentage of ASC speck-positive cells was quantified.",
    "ncbi_link": "CYLD: 74256"
  },
  {
    "caption": "LDH release from WT and Cyld KO BMDMs primed with LPS and stimulated as indicated.",
    "ncbi_link": "Cyld: 74256"
  },
  {
    "caption": "Immunoblotting analysis of active caspase-1 p20 and IL-1β in cell supernatants (Sup) and the indicated proteins in cell extracts (Cell ext) of WT iBMDMs and Spata2 KO iBMDMs reconstituted with WT Spata2 or a Spata2 mutant (F108A) defective in CYLD binding that were primed with LPS and stimulated with Nigericin for 1 h.",
    "ncbi_link": "Spata2: 263876
Spata2: 9825"
  },
  {
    "caption": "Confocal immunofluorescence analysis of Spata2 centrosome localization in HEK293 cells stably expressing control shRNA or shRNA against Spata2, stained with Spata2 and γ-tubulin antibodies and the nuclear dye DAPI. Scale bar, 10 µm.",
    "ncbi_link": "Spata2: 263876"
  },
  {
    "caption": "Confocal immunofluorescence analysis of Spata2 localization in RAW264.7 cells stably expressing GFP-Spata2, stained with γ-tubulin antibody and DAPI. Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
Spata2: 9825"
  },
  {
    "caption": "Confocal microscopy of HEK293 cells stably expressing GFP-tagged Spata2 or Spata2 mutants (ΔPUB orΔ51-81) that were stained with γ-tubulin antibody and DAPI.",
    "ncbi_link": "GFP: 
Spata2: 9825"
  },
  {
    "caption": "Confocal microscopy of HEK293 cells stably expressing GFP-tagged CYLD along with an empty vector or vectors encoding Flag-tagged Spata2 or Spata2 mutants (ΔPUB orΔ51-81) stained as in (C). Scale bar, 10 µm.",
    "ncbi_link": "Flag: 
GFP: 
CYLD: 1540
Spata2: 9825"
  },
  {
    "caption": "Co-immunoprecipitation analysis of CYLD physical interaction with Spata2 or Spata2 mutants (ΔPUB orΔ51-81) in HEK293 cells transfected with the indicated expression vectors. CYLD and Spata2 proteins were detected by immunoblot using anti-HA and anti-Flag antibodies, respectively.",
    "ncbi_link": "Spata2: 9825"
  },
  {
    "caption": "Immunoblotting analysis of the active caspase-1 p20 in cell supernatants (Sup) and pro-caspase-1 and Flag-Spata2 proteins in cell extracts (Cell ext) from WT iBMDMs and Spata2 KO iBMDMs reconstituted with WT Spata2 or Spata2 mutant defective in centrosome localization (ΔPUB orΔ51-81). Cells were primed with LPS and stimulated with Nigericin for 1 h. Data information: For all Immunoblotting data, molecular weights in kDa are indicated to the left.",
    "ncbi_link": "Spata2: 263876
Spata2: 9825"
  },
  {
    "caption": "WT and Spata2 KO iBMDMs stably expressing an empty vector or a vector encoding Flag-NEK7 were untreated (NT), primed with LPS for 4 h, or primed with LPS for 4 h followed by stimulation with Nigericin for 30 min. Flag-NEK7 was immunoprecipitated and the association of endogenous NLRP3 was assessed by immunoblotting. Relative levels of NLRP3 in immunoprecipitates were normalized to Flag-NEK7 and shown below.",
    "ncbi_link": "Flag: 
NEK7: 140609
Spata2: 263876"
  },
  {
    "caption": "Co-immunoprecipitation analysis of PLK4 interaction with endogenous Spata2 and CYLD in parental HEK293 cells and HEK293 cells stably expressing GFP-PLK4.",
    "ncbi_link": "GFP: 
PLK4: 20873"
  },
  {
    "caption": "iBMDMs stably expressing GFP-PLK4 and parental iBMDMs were unstimulated or stimulated with 0.5 ug/ml LPS for 4h. The PLK4 interaction with endogenous CYLD was analyzed by co-immunoprecipitation with anti-GFP antibody.",
    "ncbi_link": "GFP: 
PLK4: 20873"
  },
  {
    "caption": "Confocal microscopy analysis of ASC specks in iBMDMs stably expressing GFP-ASC, pretreated for 2 days with DMSO and two different PLK4 inhibitors, Centrinone (150 nM) and Centrinone-B(500 nM), primed with LPS for 4 h, and stimulated with Nigericin for 30 min. GFP-ASC specks were imaged and quantified (>500 cells counted). Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
ASC: 29108"
  },
  {
    "caption": "LPS-primed and Nigericin-stimulated iBMDMs stably expressing a control shRNA or 3 different PLK4-specific shRNAs (F).",
    "ncbi_link": "PLK4: 20873"
  },
  {
    "caption": "Immunoblot analysis of active caspase-1 (p20) generation in HEK293 cells that were transfected with inflammasome components (Flag-tagged NLRP3, NEK7, ASC, and Caspase-1) along with EGFP, GFP-tagged PLK4, PLK4 kinase dead mutant (D154A), or PLK1 and stimulated with 10 µM Nigericin for 1h 24h post-transfection.",
    "ncbi_link": "EGFP: 
Flag: 
GFP: 
Caspase-1: 12362
NEK7: 140609
NLRP3: 216799
PLK1: 5347
PLK4: 20873
ASC: 29108"
  },
  {
    "caption": "WT and Spata2 CRISPR knock out (KO) iBMDMs stably expressing GFP-ASC were pretreated with DMSO or PLK4 inhibitor Centrinone at a concentration of 150nM for 2 days, primed with LPS, and stimulated with Nigericin for 1 h. GFP-ASC specks were imaged by confocal microscope, and percentage of ASC speck-positive cells was quantified.",
    "ncbi_link": "GFP: 
ASC: 29108
Spata2: 263876"
  },
  {
    "caption": "Co-immunoprecipitation analysis of NEK7/NLRP3 interaction in iBMDMs stably expressing Flag-NEK7 that were transduced with control or PLK4-specific shRNA. The cells were untreated, primed with LPS, or primed with LPS and stimulated with Nigericin. Flag-NEK7 was immunoprecipitated and the association of endogenous NLRP3 was assessed by immunoblot analysis. Relative levels of NLRP3 in immunoprecipitates were normalized to Flag-NEK7 and shown below.",
    "ncbi_link": "Flag: 
NEK7: 140609
PLK4: 20873"
  },
  {
    "caption": "Co-immunoprecipitation analysis of NEK7/NLRP3 interaction in HEK293 cells transfected with HA-NEK7 and Flag-NLRP3 along with (+) or without (-) GFP-PLK4. The cells were either treated (+) or not treated (-) with the PLK4 inhibitor Centrinone.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
NEK7: 140609
NLRP3: 216799
PLK4: 20873"
  },
  {
    "caption": "iBMDMs stably expressing Flag-tagged NEK7 or NEK7 mutant S204A were treated with LPS. Anti-Flag immunoprecipitates were prepared for immunoblot analysis for the interaction between NEK7 and endogenous NLRP3.",
    "ncbi_link": "Flag: 
NEK7: 140609"
  },
  {
    "caption": "Immunoblot analysis of active caspase-1 (p20) in supernatants (Sup) and the indicated proteins in cell extracts (Cell ext) of iBMDMs stably expressing WT NEK7 or NEK7 mutant (S204A), primed with LPS and stimulated with nigericin.",
    "ncbi_link": "NEK7: 140609"
  },
  {
    "caption": "iBMDMs stably expressing Flag-tagged WT NEK7 or NEK7 mutant S204A were left untreated or stimulated with LPS for indicated time. Anti-Flag immunoprecipitates were prepared for immunoblot analysis for NEK7 phosphorylation at Ser 204 (P-NEK7).",
    "ncbi_link": "Flag: 
NEK7: 140609"
  },
  {
    "caption": "iBMDMs stably expressing Flag-tagged WT NEK7 were left untreated or pretreated with PLK4 inhibitor Centrinone, and stimulated without or with LPS for 4h. Anti-Flag immunoprecipitates were prepared for immunoblot analysis for NEK7 phosphorylation at Ser 204.",
    "ncbi_link": "Flag: 
NEK7: 140609"
  },
  {
    "caption": "iBMDMs stably expressing GFP-tagged PLK4 and parental iBMDMs were left untreated or stimulated with LPS for 4h. Anti-GFP immunoprecipitates were prepared for immunoblot analysis for the interaction between GFP-PLK4 and endogenous NEK7.",
    "ncbi_link": "GFP: 
PLK4: 20873"
  },
  {
    "caption": "WT and Spata2 KO iBMDMs stably expressing Flag-tagged WT NEK7 were left untreated or pretreated with the PLK4 inhibitor Centrinone, and stimulated without or with LPS for 4h. Anti-Flag immunoprecipitates were prepared for immunoblot analysis for NEK7 phosphorylation at Ser 204.",
    "ncbi_link": "Flag: 
NEK7: 140609
Spata2: 263876"
  },
  {
    "caption": "HEK293 cells stably expressing GFP-PLK4Δ24 were transfected with a control siRNA or siRNAs targeting Spata2 or CYLD. GFP-PLK4Δ24 was immunoprecipitated under denaturing conditions and immunoblotted for K63-, K48-linked and linear ubiquitination. Relative levels of PLK4 ubiquitination were normalized to GFP-PLK4 and shown below.",
    "ncbi_link": "GFP: 
CYLD: 1540
PLK4: 20873
Spata2: 9825"
  },
  {
    "caption": "Co-immunoprecipitation analysis of the PLK4-NEK7 interaction in HEK293 cells co-transfected with Flag-NEK7 and HA-PLK4 in the presence (+) or absence (-) of GFP, GFP-Spata2, GFP-CYLD, or GFP-CYLD C601S, a catalytically inactive mutant.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
CYLD: 1540
NEK7: 140609
PLK4: 20873
Spata2: 9825"
  },
  {
    "caption": "TP53INP1-KO (−/−) and WT (+/+) male mice were subjected to a high-fat diet (HFD, 60% fat) or a control diet (CTRL) for 16 weeks. Mice drank tap water or tap water supplemented with NAC (10 mg/ml or 1%).Curves show mice body weight recorded every week. CTRL: P (−/− versus +/+; t = 8w) = 0.047; P (−/− versus +/+; t = 9w) = 0.023. HFD: P (−/− versus +/+; t = 7w) = 0.039; P (−/− versus +/+; t = 8w) = 0.029; P (−/− versus +/+; t = 9w) = 0.021; P (−/− versus +/+; t = 10w) = 0.014; P (−/− versus +/+; t = 11w) = 0.0046; P (−/− versus +/+; t = 12w) = 0.0028; P (−/− versus +/+; t = 13w) = 0.0025; P (−/− versus +/+; t = 14w) = 0.00051; P (−/− versus +/+; t = 15w) = 0.00027; P (−/− versus +/+; t = 16w) = 0.00013.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "C-E Quantitative PCR for Tp53inp1 mRNA levels in tissues and cells from rat (C) and C57BL/6Jmice fed with a normal diet (5% fat; ND) or an high-fat diet (45% fat; HFD) (D, E). Results are expressed as the mean ± SEM and are representative of two independent experiments. n = 2 for ratliver, islets and mousespleen; n = 4 for INS-1E cells; n = 5 for mouseexocrine pancreas; n = 6 for Min6 cells and ND and HFD islets; n = 11 for mouseislets. *P = 0.035 for HFD versus ND.",
    "ncbi_link": "Tp53inp1: 60599"
  },
  {
    "caption": "Immortalized MEFs (MEFi) deficient (−/−) or not (+/+) for TP53INP1 were left untreated (NT) or treated with 3-methyladenine (3-MA, 5 mM) during 4 h.Histograms show mt ROS level measured by flow cytometry upon MitoSox staining. P (−/− versus +/+; NT) = 0.019; P (−/− versus +/+; 3-MA) = 0.025; P (3-MA versus NT; +/+) = 0.031.Histograms show mt mass evaluated by flow cytometry in KO or WT MEFi using MitoTracker staining. P (−/− versus +/+; NT) = 0.012; P (3-MA versus NT; +/+) = 0.036.Histogram shows MitoSox fluorescence normalized with MitoTracker fluorescence. P (−/− versus +/+; NT) = 0.041; P (−/− versus +/+; 3-MA) = 0.030; P (3-MA versus NT; +/+) = 0.045.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "After 4 h recovering in normal media, H2O2 (1 h, 100 μM) or non-treated (NT) MEFi deficient (−/−) or not (+/+) for TP53INP1 were observed by transmission electron microscopy (TEM). N = nucleus; white arrow = mitophagic vacuoles. Scale bar represents 0.5 μm.Mean size of mitochondrion (area), number of mitochondria and mitophagic vacuoles normalized by cytoplasmic surface area were quantified. Size: P (−/− versus +/+; H2O2) = 0.000027; P (H2O2 versus NT; +/+) = 0.0070; P (H2O2 versus NT; −/−) = 0.013. Nb mito.: P (−/− versus +/+; NT) = 0.035; P (−/− versus +/+; H2O2) = 0.016. Nb vacuoles.: P (−/− versus +/+; NT) = 0.047.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "After 4 h recovering in normal media, TCLs from H2O2- (1 h, 100 μM), NAC- (24 h, 10 mM) or non-treated (NT) MEFi deficient (−/−) or not (+/+) for TP53INP1 were analyzed by immunoblotting for PGC-1α, PINK1, PARKIN, BNIP3, BNIP3L/NIX, VDAC1 and β-tubulin.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "HEK293T cells were cotransfected with plasmids encoding TP53INP1α-NTAP or TP53INP1β-NTAP. TP53INP1α- or β-NTAP was precipitated with a streptavidin-containing resin (P), resolved by PAGE and Western blots developed with anti-TP53INP1 (TP53INP1 precipitation control), anti-PINK1, anti-PARKIN, anti-BNIP3 or anti-BNIP3L/NIX antibody. Western blot on TCL (on the right) served as a transfection control.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "Three-month-old TP53INP1-deficient and WT male mice were sacrificed and their livers harvested. Mitochondrial lysates (Mito) were purified from total liver lysates (TCL), and both were analyzed by immunoblotting for TP53INP1, PINK1, PARKIN, VDAC1 and β-tubulin.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "A-D High-resolution respirometry was performed on permeabilized MEFi TP53INP1 deficient (−/−, black bars) or not (+/+, white bars) using glucose (A), lipid-related substrates (C) or complex IV substrate (D). High-resolution respirometry was also performed on intact MEFi (B). For different respiratory state details (routine, 3, leak, and ETS capacity), please refer to the Materials and Methods section. Results are expressed as the mean ± SEM and are representative of three independent experiments. In (A): P (−/− versus +/+; State 3) = 0.0079; P (−/− versus +/+; ETS) = 0.0079; n = 5 in each group. In (B): P (−/− versus +/+; routine) = 0.0159; P (−/− versus +/+; leak) = 0.0159; P (−/− versus +/+; ETS) = 0.0159; n = 5 in each group. In (C): P (−/− versus +/+; State 3) = 0.029; P (−/− versus +/+; ETS) = 0.0079; n = 5 in each group. In (D): P (−/− versus +/+; ETS) = 0.0259; n = 5 in each group. *TP53INP1−/− versus TP53INP1 +/+; 1 character: P < 0.05; 2 characters: P < 0.01.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "MEFi deficient (−/−) or not (+/+) for TP53INP1 were seeded in media containing or not 10 mM NAC. Forty-eight hours later, MEFi were treated or not (NT) with 100 μM hydrogen peroxide (H2O2) during 1 h in serum free media. Cells were left to recover for 4 h in normal media containing or not NAC (10 mM), GW-9662 (PPARγ inhibitor, 10 μM) or PNU-74654 (Wnt/β-catenin pathway inhibitor, 50 μM) before being harvested. Cells were observed by TEM.Number of LD normalized by cytoplasmic surface area is shown in both histograms at the bottom of the figure. Scale bar represents 0.5 μm. Results are expressed as the mean ± SEM and are representative of three independent experiments. *P (−/− versus +/+; NT) = 0.00086; #P (H2O2 versus NT; +/+) = 0.013.",
    "ncbi_link": "TP53INP1: 60599"
  },
  {
    "caption": "Human peripheral blood mononuclear cells (PBMCs) were cultivated for 48h in RPMI containing 80mg/dl glucose (NC) and supplemented with 10mM beta-hydroxybutyrate (BHB). T cell  stimulation was performed through  CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. Human  pan T cell RNA was isolated and cell culture supernatant was sampled. A mRNA expression  of CD4+  cytokines  Il2, IL4,  IL8 and IL22 relative to endogenous controls, n=13/11/10/8 biological replicates. Data information: Data depicted as mean ± SEM (protein data) and box plots with median, twenty-fifth and seventy-fifth percentiles and range (all other). Dots indicating individual values. *p<0.05, **p<0.01, ***p<0.001, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "IL8: 3576
Il2: 3558
IL22: 50616
IL4: 3565"
  },
  {
    "caption": "Human peripheral blood mononuclear cells (PBMCs) were cultivated for 48h in RPMI containing 80mg/dl glucose  (NC) and supplemented with 10mM beta-hydroxybutyrate (BHB). T cell  stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8.  Human pan T cell RNA was isolated and cell culture supernatant was sampled. D mRNA expression of CD8+ cytokines IFNγ,  PRF1,  TNFα, GZMB and CTLA4  in stimulated human T cells relative to internal controls, n=15/14/10/14/9 biological replicates. Data information: Data depicted as mean ± SEM (protein data) and box plots with median, twenty-fifth and seventy-fifth percentiles and range (all other). Dots indicating individual values. *p<0.05, **p<0.01, ***p<0.001, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "CTLA4: 1493
GZMB: 3002
IFNγ: 3458
PRF1: 5551
TNFα: 7124"
  },
  {
    "caption": "Human peripheral blood mononuclear cells  (PBMCs) were cultivated for 48h in RPMI containing 80mg/dl glucose (NC) and supplemented with 10mM beta-hydroxybutyrate (BHB). T cell  stimulation was performed through CD3/CD28 Dynabeads  at a bead:cell ratio of 1:8. Human pan T cell RNA was isolated and cell culture supernatant was sampled. F  Foxp3 mRNA relative to internal control in human PBMCs and quantification of CD4+CD25+Foxp3+ regulatory T cells (Treg) following 5 days of Treg differentiation with a representative  Foxp3  histogram plot (right side), n=7/11 biological replicates. Data information: Data depicted as mean ± SEM (protein data) and box plots with median, twenty-fifth and seventy-fifth percentiles and range (all other). Dots indicating individual values. *p<0.05, **p<0.01, ***p<0.001, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "Foxp3: 50943"
  },
  {
    "caption": "Human peripheral blood mononuclear cells  (PBMCs) were cultivated for 48h in RPMI containing 80mg/dl  glucose  (NC) and supplemented with 10mM beta-hydroxybutyrate (BHB). T cell  stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. Human pan T cell RNA was isolated and cell culture supernatant was sampled. G  IL10 and TGFβ1 mRNA and protein expression of  human Treg cells, n=8/9 (IL10), 5/9 (TGFβ1) biological replicates. Data information: Data depicted as mean ± SEM (protein data) and box plots with median, twenty-fifth and seventy-fifth percentiles and range (all other). Dots indicating individual values. *p<0.05, **p<0.01, ***p<0.001, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate. ",
    "ncbi_link": "IL10: 3586
TGFβ1: 7040"
  },
  {
    "caption": "Healthy volunteers conducted a three week KD with a limited carbohydrate  consumption of <30g per day. Blood was taken and analyzed prior to (T0) and post KD (T1). PBMCs were isolated. T cell  stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. CD4+/CD8+ T cells were separated via magnetic cell labeling. A IL2, IL4, and CTLA4 mRNA expression in stimulated CD4+ T cells, n=17/18/17 individual human subjects. Data information: Data depicted as box plots with median, twenty-fifth and seventy-fifth percentiles and range. Dots indicating individual values. *p<0.05, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "CTLA4: 1493
IL2: 3558
IL4: 3565"
  },
  {
    "caption": "Healthy volunteers conducted a three week KD with a limited carbohydrate consumption of <30g per day. Blood  was taken and analyzed prior to (T0) and post KD (T1). PBMCs were isolated.  T cell  stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. CD4+/CD8+ T cells were separated via magnetic cell labeling. B Tbet and GATA3 mRNA expression in CD4+ T cells, n=7 individual human  subjects. Data information: Data depicted as box plots with median, twenty-fifth and seventy-fifth percentiles and range. Dots indicating individual values. *p<0.05, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "GATA3: 2625
Tbet: 30009"
  },
  {
    "caption": "Healthy volunteers conducted a three week KD with a limited  carbohydrate consumption of <30g per day. Blood  was taken and analyzed prior to (T0) and post KD (T1). PBMCs were isolated. T cell stimulation was performed through CD3/CD28 Dynabeads  at a bead:cell ratio of 1:8. CD4+/CD8+ T cells were separated via magnetic cell labeling. D IL10 mRNA expression and flow cytometric quantification of CD4+CD25+Foxp3+ regulatory T cells (Treg), n=19/9individual human subjects. Data information: Data depicted as box plots with median, twenty-fifth and seventy-fifth percentiles and range. Dots indicating individual values. *p<0.05, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "IL10: 3586"
  },
  {
    "caption": "Healthy volunteers conducted a three week KD with a limited  carbohydrate consumption of <30g per day. Blood was taken and analyzed prior to (T0) and post KD (T1). PBMCs were isolated. T cell  stimulation was performed through CD3/CD28 Dynabeads at a bead:cell ratio of 1:8. CD4+/CD8+ T cells were separated via magnetic cell labeling. E IFNγ GZMB, PRF1 and CTLA4 mRNA expression in CD8+ T cells, n=16/18/17/17 individual human subjects. Data information: Data depicted as box plots with median, twenty-fifth and seventy-fifth percentiles and range. Dots indicating individual values. *p<0.05, paired t-test/ Wilcoxon matched-pairs signed rank test, as appropriate.",
    "ncbi_link": "CTLA4: 1493
GZMB: 3002
IFNγ: 3458
PRF1: 5551"
  },
  {
    "caption": "RT-qPCR analysis of Sall4, Cdh1, Epcam and Esrrb gene expression in MEFs, intermediate cells on d12 treated with DMSO and R406, and R1 (mESCs). n = 3.",
    "ncbi_link": "Cdh1: 12550
Epcam: 17075
Esrrb: 26380
Sall4: 99377"
  },
  {
    "caption": "Immunofluorescence of Sall4 in reprogramming intermediates infected with shNC and shSyk. n = 3. Scale bar, 100 μm.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "Immunofluorescence of Sall4 in WT cells and Ppp3ca knockdown cells on d12. n = 6. Scale bar, 100 μm. RT-qPCR analysis of pluripotent genes expression in cells treated with shNC and shPpp3ca. n = 3.",
    "ncbi_link": "Ppp3ca: 19055"
  },
  {
    "caption": "Immunofluorescence of Sall4 in WT cells and Nfatc1 knockdown cells on d12. n = 3. Scale bar, 100 μm. RT-qPCR analysis of pluripotent genes expression in cells treated with shNC and shNfatc1. n = 3.",
    "ncbi_link": "Nfatc1: 18018"
  },
  {
    "caption": "RT-qPCR analysis of Gldc, Cbs and Tdh expression in R406- and shSyk-treated cells (E) and FK506-, shPpp3ca- and shNfatc1-treated cells (F) on d8. n = 3.",
    "ncbi_link": "Cbs: 12411
Gldc: 104174
Nfatc1: 18018
Ppp3ca: 19055
Syk: 20963
Tdh: 58865"
  },
  {
    "caption": "RT-qPCR analysis of Sall4, Cdh1, Epcam and Esrrb gene expression in DPBS- and HA-treated cells on d12. n = 3. RT-qPCR analysis of Sall4, Cdh1, Epcam and Esrrb gene expression in DPBS- and NAC-treated cells on d12. n = 3.",
    "ncbi_link": "Cdh1: 12550
Epcam: 17075
Esrrb: 26380
Sall4: 99377"
  },
  {
    "caption": "Immunofluorescence of Sall4 in WT cells and Cbs overexpressing cells on d12. n = 4. Scale bar, 100 μm.",
    "ncbi_link": "Cbs: 12411"
  },
  {
    "caption": "(A) RT-qPCR of early passage RMS tumoroid  models shows positivity for at least one gene used in standard-of-care pathology analysis (DES, MYOG, or MYOD1). Conventional RMS  cell lines (RD  and RH30) were used as positive controls, while two  Synovial Sarcoma (SS000DAZ  and SS077) tumoroid  models were used as negative controls. Gene expression was normalized to the expression of a house-keeping gene and human  reference RNA (HREF) via the ΔΔCq method. Each tumoroid  line was measured once with four technical replicates with the error bars representing the standard deviation of said technical replicates.",
    "ncbi_link": "DES: 1674
MYOD1: 4654
MYOG: 4656"
  },
  {
    "caption": "(B)  Western Blot analysis of TP53  wildtype (WT) and knockout (KO) RMS  tumoroid line   RMS012. Histone 3 (H3) served as loading control.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "(C)  Dose-response curve of TP53  WT and KO cells treated with the Chk-1 inhibitor prexasertib. Thin lines with numbers indicate individual biological replicates (n = 3) while thick lines indicate fitted lines over all replicates. The statistical significance of the differences in fitted IC50  values between WT and KO were obtained using a two-sided t-test (p = 0.008).",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "B. Confocal microscopy images of PrimPol and γH2AX (damage control) immunofluorescence staining in control (UVA) or TMP-UVA-laser irradiated (10 µM TMP, 2 h followed by UVA laser irradiation) WT and PRIMPOL KO cells. Nuclear DNA is counterstained with DAPI. UVA laser path is indicated. Scale bar, 10 µm. Histograms (right panel) show the average percentage of PrimPol-positive cells and SD of three assays (n ≥100 cells per TMP-treated conditions in each replicate). Circle dots in each column represent the values of individual replicates. Statistical analysis was conducted with one-way ANOVA followed by Bonferroni post-test. p-values of individual comparisons are indicated.",
    "ncbi_link": "PRIMPOL: 201973"
  },
  {
    "caption": "C. Confocal microscopy images of PrimPol  and γH2AX  (damage control) immunofluorescence staining in control (UVA) or TMP-UVA-treated cells following control or RPA2 downregulation. Nuclear DNA is  counterstained with DAPI. UVA laser path is indicated. Scale bar, 10 µm. Histograms (right panel) show the average PrimPol-positive cells and SD of three assays (n ≥100 cells per TMP-treated conditions in each replicate). Circle dots in each column represent the values of individual replicates. Statistical analysis was conducted with one-way ANOVA followed by Bonferroni post-test. p-values of individual comparisons are indicated.",
    "ncbi_link": "RPA2: 6118"
  },
  {
    "caption": "D. Confocal microscopy images of PrimPol  and γH2AX  (damage control)  immunofluorescence staining in control (UVA) or TMP-UVA-treated PRIMPOL KO cells stably expressing V5-tagged WT or  RPA binding domain mutant (RBDm) PrimPol  versions. Nuclear DNA is  counterstained with DAPI. UVA laser path is indicated. Scale bar, 10 µm. Histograms (right panel) show the average percentage of PrimPol-positive cells and SD of two assays (n ≥100 cells per condition in each replicate). Circle dots in each column represent the values of individual replicates. Statistical analysis was conducted with one-way ANOVA followed by Bonferroni post-test. p-values of individual comparisons are indicated.",
    "ncbi_link": "V5: 
PRIMPOL: 201973
PrimPol: 201973"
  },
  {
    "caption": "E.  Confocal microscopy images  of  PrimPol and γH2AX (damage control) immunofluorescence staining in control (UVA) or TMP-UVA-treated WT and BLM KO cells upon downregulation of TOP3A, RMI1 and RMI2 (siTR) when indicated. Nuclear  DNA is counterstained with DAPI. UVA laser path  is indicated. Scale bar, 10 µm. Histograms (right panel) show the average percentage of PrimPol-positive cells and SD of three assays (n ≥250 cells per condition). Circle dots in each column represent the values of individual replicates. Statistical analysis was conducted with one-way ANOVA followed by Bonferroni post-test.",
    "ncbi_link": "BLM: 641
RMI1: 80010
RMI2: 116028
TOP3A: 7156"
  },
  {
    "caption": "H. Immunoblots showing the levels of BLM, FANCD2 and PrimPol after BLM  or FANCD2 downregulation in WT and PRIMPOL KO cells for experiments in (G). Ponceau-S  is shown as loading control.",
    "ncbi_link": "BLM: 641
FANCD2: 2177
PRIMPOL: 201973"
  },
  {
    "caption": "C. Representative confocal microscopy images  of  EdU staining in WT and PRIMPOL KO cells, 8 h after  UVA (control) or TMP-UVA treatment (2 µM TMP, 2 h followed by 5 s irradiation).  Nuclear DNA is  counterstained with  DAPI. When indicated, V5-PrimPol  was reintroduced into KO cells. Scale bar, 25 µm. Dot plots indicate the distribution of nuclear EdU intensity, and the mean values are indicated by horizontal red lines. Data from the combination of three replicates (n ≥200 cells per condition). Statistical analysis was conducted with Kruskal-Wallis test and Dunns post-test. p-values of individual comparisons are indicated.",
    "ncbi_link": "V5: 
PRIMPOL: 201973
PrimPol: 201973"
  },
  {
    "caption": "A. Confocal microscopy images  of FANCD2 immunofluorescence staining in control (UVA) or TMP-UVA-treated (2 µM TMP, 2 h followed by 5 s irradiation) WT and PRIMPOL KO cells. Nuclear DNA is counterstained  with DAPI. Scale bar, 25 µm.",
    "ncbi_link": "PRIMPOL: 201973"
  },
  {
    "caption": "A. Kaplan-Meier survival curves of WT and PRIMPOL  KO  mice after the administration of a single  dose of MMC (7.5, 10 or 15 mg/kg). Dashed vertical lines represent median  survival values for WT (blue) and KO (orange)  mice. Statistical analysis was conducted with Log-rank (Mantel-Cox) test; p-value for the highest dose of MMC (15 mg/kg) is indicated.",
    "ncbi_link": "PRIMPOL: 408022"
  },
  {
    "caption": "B. Haematoxylin-eosin (H&E) and Ki-67 immunohistochemistry (IHC) stainings of bone marrow  sections derived from WT and PRIMPOL KO mice following the administration of 10 mg/kg  MMC. Control mice (PBS) were sacrificed when MMC-injected mice reached the humane endpoint. Scale bar, 2.5 mm. In each  image, a relevant area is shown at higher magnification (10x).",
    "ncbi_link": "PRIMPOL: 408022"
  },
  {
    "caption": "E. IF detection of FANCD2 foci in WT and  PRIMPOL  KO cells 48 h after TMP-UVA (2 µM TMP, 2 h followed by 5 s irradiation) with or without MCM3 downregulation. Nuclear DNA is counterstained with DAPI. Scale bar, 25 µm.",
    "ncbi_link": "MCM3: 4172
PRIMPOL: 201973"
  },
  {
    "caption": "G. Cell survival assays of WT and PRIMPOL KO cells with or without MCM3 downregulation in the presence of increasing amounts of MMC  or TMP (followed by 90 sec UVA irradiation) for 72 h. The same control curves without MCM3 downregulation are also shown as part of Figure EV6D. Each point in the curve represents the percentage of surviving cells (average and SD of three assays for MMC and two assays for TMP). Statistical analysis was conducted with two-way ANOVA followed by Bonferroni post-test. p-values of comparisons between KO and KO-siMCM3 are indicated.",
    "ncbi_link": "MCM3: 4172
PRIMPOL: 201973"
  },
  {
    "caption": "(a) Pseudocolour-coded images of EPACI-camps FRET from real-time imaging of wild-type MEFs transfected with EPACI-camps. Where indicated, cells were perfused with the starvation solution for the indicated times (in min) or with 25 μM forskolin (FRSK). Scale bar, 20 μm. Colour scale indicates F1/F0 ratio. See also Supplementary Movie S3. (b) Quantitative analysis of CFP/YFP FRET ratio. Experiments were carried out as in a. Where indicated, cells were perfused with the starvation solution or with 25 μM forskolin. Data represent mean ± s.e.m. of 13 independent experiments.",
    "ncbi_link": "EPACI–camps: "
  },
  {
    "caption": "(d) Representative images of the effect of H89 on mitochondrial morphology on starvation. Wild-type and Mfn2−/−MEFs were transfected with mtYFP, and after 24 h confocal micrographs were acquired. Where indicated, cells were starved for 2.5 h and 20 μM H89 was added. Scale bar, 20 μm. (e) Morphometric analysis. Experiments were carried out as in d. Data represent mean ± s.e.m. of five independent experiments (n=100 cells per condition).",
    "ncbi_link": "Mfn2: 170731"
  },
  {
    "caption": "(f) Starvation-induced mitochondrial elongation depends on Ser 637 of DRP1. Representative confocal micrographs of mitochondrial morphology of wild-type MEFs co-transfected with mtRFP and the indicated plasmids. At 24 h after transfection, where indicated cells were starved for 2.5 h and imaged. Where indicated, 20 μM H89 was present during starvation. Scale bar, 20 μm. (g) Morphometric analysis of mitochondrial shape. Experiments were carried out as in f. Data represent mean ± s.e.m. of five independent experiments (n=50 cells per condition).",
    "ncbi_link": "DRP1: 74006"
  },
  {
    "caption": "(h) Representative confocal micrographs of mitochondrial morphology of Drp1−/− MEFs co-transfected with mtRFP and the indicated plasmids. At 24 h after transfection, where indicated cells were starved for 2.5 h and imaged. Where indicated, 20 μM H89 was present during starvation. Scale bar, 20 μm. (i) Morphometric analysis of mitochondrial shape. Experiments were carried out as in h. Data represent mean ± s.e.m. of five independent experiments (n=50 cells per condition).",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": "(d) Mitochondrial ATP measured in situ by mitochondrially targeted luciferase in cells of the indicated genotype starved for the indicated times. Data represent mean ± s.e.m. of five independent experiments and are normalized to the initial value.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(i) Drp1−/− MEFs were transfected with the indicated plasmids and after 24 h starved for 5 h where indicated. Cell death was determined by flow cytometry as the percentage of YFP- and propidium-iodide-positive events. Data represent mean ± s.e.m. of four independent experiments.",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": "Polysome profiles of mouse intestinal crypt treated with or without Wnt3a for 30 min. The right panels show the distributions of Ythdf1 and Actb in polysome fractions. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (3 biological replicates, t-test).",
    "ncbi_link": "Actb: 11461
Ythdf1: 228994"
  },
  {
    "caption": "Immunoblot analysis of SW620 cells with or without APC overexpression. The relative protein level was quantified and shown under each band.",
    "ncbi_link": "APC: 324"
  },
  {
    "caption": "Polysome profiles of SW620 cells with or without APC overexpression. The right panels show the distributions of YTHDF1 and ACTB in polysome fractions. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (3 biological replicates, t-test).",
    "ncbi_link": "ACTB: 60
APC: 324
YTHDF1: 54915"
  },
  {
    "caption": "Dual-Luciferase assay wih a construct bearing the 5'UTR of YTHDF1 in SW620 cells with or without APC overexpression. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (3 biological replicates, t-test).",
    "ncbi_link": "APC: 324
YTHDF1: 54915"
  },
  {
    "caption": "YTHDF1 protein expression in intestinal tissue from 4 pairs of Apc+/+ and Apcmin/+ mice. N, normal tissue. T, tumor tissue. A, tumor adjacent tissue.",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "The representative jejunum from wildtype (Ythdf1CTL) and Ythdf1cKO mice. Left: hematoxylin and eosin staining (H&E); middle: BrdU staining; right: quantification of crypt height and BrdU+ cells. Scale bar, 50 μm. Data are represented as mean ± SEM. (9 biological replicates, t-test).",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "Immunoblot analysis of small intestines from Ythdf1CTL and Ythdf1cKO mice after 12 Gy IR.",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "Small intestines from Ythdf1CTL and Ythdf1cKO mice 72 hr after 12 Gy IR. Left: H&E staining; middle: Ki67 staining; right: quantification of crypt height and Ki67+ cells. Scale bar, 50 μm. Vertical bars indicate the length of the crypts. Data are represented as mean ± SEM. ****p<0. 0001 (9 biological replicates, t-test).",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "RT-qPCR analysis of small intestines from Ythdf1CTL and Ythdf1cKO mice 72 hr after 12 Gy IR. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (5 biological replicates, t-test).",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "Small intestines from 24-week-old Apcmin/+; Ythdf1CTL and Apcmin/+; Ythdf1cKO mice.",
    "ncbi_link": "Apc: 11789
Ythdf1: 228994"
  },
  {
    "caption": "H&E staining of small intestines from 24-week-old Apcmin/+; Ythdf1CTL and Apcmin/+; Ythdf1cKO mice. Scale bar, 1 mm. The black arrows indicate the tumors.",
    "ncbi_link": "Apc: 11789
Ythdf1: 228994"
  },
  {
    "caption": "Tumor number (C) and size distribution (D) from the small intestines of 24-week-old Apcmin/+; Ythdf1CTL and Apcmin/+; Ythdf1cKO mice. Data are shown as mean ± SEM (6 mice for each group). **p<0. 01, ***p<0. 001 (t-test).",
    "ncbi_link": "Apc: 11789
Ythdf1: 228994"
  },
  {
    "caption": "Colons from Ythdf1CTL and Ythdf1cKO mice on day 84 of AOM/DSS induction.",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "H&E staining of colons from Apcmin/+; Ythdf1CTL and Apcmin/+; Ythdf1cKO mice after AOM/DSS induction. Scale bar, 200 μm.",
    "ncbi_link": "Apc: 11789
Ythdf1: 228994"
  },
  {
    "caption": "Colon tumor number (H) and size distribution (I) from Ythdf1CTL and Ythdf1cKO mice on day 84 of induction. Data are shown as mean ± SEM (6 mice for each group). **p<0. 01 (t-test).",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "Fluorescent in situ hybridization for Ythdf1 mRNA in Ythdf1CTL and Ythdf1cKO small intestines. Scale bar, 50 μm.",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "Flowcytometry analysis of YTHDF1 protein expression in GFPhigh/low/neg populations from Lgr5-GFP-IRES-creERT2 mice.",
    "ncbi_link": "GFP: 
cre: 2777477
ERT2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Morphology of organoids from Lgr5-creERT2:Ythdf1fl/fl mice in Wnt3a-conditioned medium without or with 4-OHT induction and infected with lentivirus expressing YTHDF1 or YTHDF1 mutant. Scale bar, 250 μm.",
    "ncbi_link": "cre: 2777477
ERT2: 2099
Lgr5: 14160
Ythdf1: 228994
YTHDF1: 228994"
  },
  {
    "caption": "Scatterplot of mRNA expression and ribosome profiling data from control and YTHDF1 knockdown cells. The upregulated (red) and downregulated (blue) genes in translational efficiency (TE) are highlighted.",
    "ncbi_link": "YTHDF1: 54915"
  },
  {
    "caption": "The relative m6A peak coverage in control cells for transcripts grouped according to TE changes after YTHDF1 knockdown. POI: peak over input. Down, genes significantly downregulated in YTHDF1 knockdown cells (<0.5 fold). Unchanged, genes not significantly changed. Up, genes significantly upregulated (>2 fold). The upper and lower quartiles and the median are shown for each group. Mann-Whitney test. **p<0. 01. ***p<0. 001.",
    "ncbi_link": "YTHDF1: 54915"
  },
  {
    "caption": "Violin plots showing TE change between control and YTHDF1 knockdown cells for not-methylated (non-m6A) and methylated (m6A) transcripts. The upper and lower quartiles and the median are indicated for each group. Mann-Whitney test.",
    "ncbi_link": "YTHDF1: 54915"
  },
  {
    "caption": "Heatmap showing the TE of Wnt signaling components in control and YTHDF1 knockdown cells. The values show the fold change of the indicated color of the heatmap.",
    "ncbi_link": "YTHDF1: 54915"
  },
  {
    "caption": "Immunoblot analysis of HCT116 cells with YTHDF1 knockdown. Two major bands were detected for human TCF7L2 due to alternative splicing.",
    "ncbi_link": "YTHDF1: 54915"
  },
  {
    "caption": "Polysome profiles of HCT116 cells with or without YTHDF1 knockdown. The right panels show the distributions of TCF7L2, and ACTB in polysome fractions. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01 (3 biological replicates, t-test).",
    "ncbi_link": "ACTB: 60
TCF7L2: 6934
YTHDF1: 54915"
  },
  {
    "caption": "Immunoblot analysis of crypts from Ythdf1CTL and Ythdf1cKO mice. Multiple bands were detected for mouse TCF7L2 representing different isoforms.",
    "ncbi_link": "Ythdf1: 228994"
  },
  {
    "caption": "MeRIP-qPCR analysis of m6A levels of TCF7L2 in crypts treated with or without Wnt3a. Data are represented as mean ± SEM. *p<0. 05 (3 biological replicates, t-test).",
    "ncbi_link": "TCF7L2: 21416"
  },
  {
    "caption": "RIP analysis of the interaction of YTHDF1 with TCF7L2 mRNA. The enrichment was measured by qPCR and normalized to input. Data are represented as mean ± SEM. *p<0. 05 (3 biological replicates, t-test).",
    "ncbi_link": "TCF7L2: 21416"
  },
  {
    "caption": "β-catenin/TCF4 reporter activity in YTHDF1 knockdown cells infected with lentivirus expressing TCF7L2. Data are represented as mean ± SEM. *p<0. 05, **p<0. 01, ***p<0.001 (3 biological replicates, t-test).",
    "ncbi_link": "β-catenin: 12387
TCF4: 21413
TCF7L2: 21416
YTHDF1: 228994"
  },
  {
    "caption": "Morphology of organoids from Lgr5-creERT2:Ythdf1fl/fl mice in Wnt3a-conditioned medium without or with 4-OHT induction and infected with lentivirus expressing TCF7L2. Scale bar, 250 μm. Quantification of differentiated versus undifferentiated organoids from (H). Data are represented as mean ± SEM. **p<0. 01, ***p<0. 001 (3 biological replicates, t-test).",
    "ncbi_link": "cre: 2777477
ERT2: 2099
Lgr5: 14160
TCF7L2: 21416
Ythdf1: 228994"
  },
  {
    "caption": "Kaplan-Meier survival plots for Apcmin/+; Lgr5-creERT2:Ythdf1fl/fl mice (8 mice for each group) treated with or without TAM. Log-rank (Mantel Cox) test. **p<0. 01 (t-test).",
    "ncbi_link": "Apc: 11789
cre: 2777477
ERT2: 2099
Lgr5: 14160
Ythdf1: 228994"
  },
  {
    "caption": "B. Detection of sFn14  in conditioned media. HEK293E  cells were transfected with either empty vector or a plasmid encoding human Fn14  that bears an N-terminal HA-tag and a C-terminal double FLAG-tag. Conditioned media  and lysates  of the transfected cells were collected and analyzed by immunoblotting  with the indicated antibodies. Calnexin  served as a loading control. Shown are representative blots  from N=3 experiments.",
    "ncbi_link": "FLAG: 
HA: 
Fn14: 51330"
  },
  {
    "caption": "C. Generation of sFn14 is sensitive to the γ-secretase  inhibitor DAPT. HEK293E  cells were transfected with either Fn14  or C99  (C-terminal fragment of APP), both containing a N-terminal HA-tag and C-terminal double FLAG-tag. One day after transfection, cells were treated with γ-secretase  inhibitor DAPT  (1 μM), broad-spectrum metalloprotease  inhibitor TAPI-1 (50 μM), or the corresponding amount of vehicle DMSO  as indicated. The conditioned media and the lysates  were blotted  with anti-HA  antibody. Shown are representative blots   from N=4 experiments.",
    "ncbi_link": "FLAG: 
HA: 
APP: 351
Fn14: 51330"
  },
  {
    "caption": "E. In vitro γ-secretase cleavage assay. HEK293E  cells were transfected with epitope-tagged Fn14  or C99. Cellular membranes were collected and incubated under indicated conditions for the γ-secretase activity assay. Reactions were terminated and ultracentrifuged. Supernatant (containing  γ-secretase cleavage products) was used for detecting the ICD fragment while the pellet was used to blot  for full length proteins Fn14  or C99. Blotting  is done by anti-Flag  antibody. Shown are representative blots  from N=3 experiments.",
    "ncbi_link": "Fn14: 51330"
  },
  {
    "caption": "F. sFn14  production requires the proteolytic presenilin  subunit of γ-secretase. HEK293  cells stably transfected with APP  carrying the Swedish double mutation (K595N/M596L) and with a CRISPR/CAS9-mediated knockout of  presenilin 1 (PS1  KO) or of both PS1  and PS2  (PS1/2 dKO), were transiently transfected with epitope-tagged Fn14. Conditioned media and lysates  of the transfected cells were blotted  with the indicated antibodies. C83 is a small C-terminal fragment of APP  (containing the C-terminal 83 amino acids), which is also subjected to  γ-secretase  processing. Upon longer exposure, the C99 (generated by BACE1  from APP) is also visible in the PS1/2 dKO condition. Shown are representative blots  from N=4 experiments. G. Quantification of results from panel F. sFn14  levels in the conditioned media quantified and normalized to WT sFn14 signal. Data Information: Panel (G) shows mean ± SEM, along with p-values calculated by ordinary one-way ANOVA test with Tukey's multiple comparison test.",
    "ncbi_link": "CRISPR: 
APP: 351
CAS9: 69900935
presenilin 1: 5663
PS1: 5663
PS2: 5664
Fn14: 51330"
  },
  {
    "caption": "A. MDA-MB-231 cells were transfected with an siRNA pool against human Fn14  or non-targeting control (Ctrl) siRNA. A day after transfection, the cells were treated with  γ-secretase inhibitor DAPT  (1 μM) or vehicle overnight. The lysate was collected and blotted  against Fn14  (C-terminal antibody) or calnexin  as loading control. Shown are representative blots  from N=4 experiments. B. Quantification of blot  in panel A. The control condition where the cells were only treated with vehicle DMSO  and non-targeting siRNA (DMSO  + siCtrl) was used as baseline, and its average normalized to 1. N=4 experiments. Data information: All quantification data is shown as mean ± SEM. The tested conditions were compared against control (DMSO  + siCtrl) condition by ordinary one-way ANOVA and Dunnett's multiple comparison test. The p-values that are above 0.05 have not been included into the panels.",
    "ncbi_link": "Fn14: 51330"
  },
  {
    "caption": ") Animals harboring CRISPR-generated deletion alleles in y48g1c.1 (gg682 or gg683) were treated with dpy-11 RNAi and progeny, grown in the absence of dpy-11 RNAi, were scored for Dpy. Percentage of Dpy animals is shown. N=3, error bar is standard deviation, s.d.",
    "ncbi_link": "CRISPR: 
dpy-11: 179040
Dpy: 179040
y48g1c.1: 171599"
  },
  {
    "caption": "E) Fluorescence micrograph of GFP::ZNFX-1 and PGL-1::TagRFP fluorescence in animals harboring a CRISPR-generated deletion allele (gg682) in y48g1c.1. Scale bar, 5μm.",
    "ncbi_link": "CRISPR: 
y48g1c.1: 171599"
  },
  {
    "caption": "Z-stack confocal images from pachytene germ cells from animals of the indicated genotypes were analysed as described to determine; the size of P or Z granules (panel C); or the number of P or Z granules surrounding a typical nucleus in wild-type and zsp-1(gg682) animals (panel D). Granules from 9 total nuclei from 3 different animals (3 cells per animal) were quantified for these analyses. Black lines indicate mean of all data points in each group. P value, student's t test, two tailed.",
    "ncbi_link": "zsp-1: 171599"
  },
  {
    "caption": "A) Heat map showing recovery of ZNFX-1 fluorescence after photobleaching in Z granules from pachytene stage adult germ cells from wild-type or zsp-1(gg682) mutant animals. Scale bar, 0.5 μm. B) Normalized recovery of fluorescence after photobleaching of GFP::ZNFX-1 in wild-type or zsp-1(-) mutant animals over indicated time points. Bleaching event occurred at 0s. Data are represented as ± s.e.m. of n=13, and n=16 individual granules from wild-type and zsp-1(gg682) animals, respectively. ",
    "ncbi_link": "zsp-1: 171599"
  },
  {
    "caption": "F) oma-1(zu405) is a temperature sensitive (ts) lethal (embryonic arrest at temperatures > 20°C) allele of oma-1 (R. Lin 2003). oma-1 RNAi suppresses oma-1(zu405ts) lethality. Animals were exposed to oma-1 RNAi and the number of embryos that hatched was scored at 20°C. N=3. Error bars are +/- s.d. Animals harboring mutations in genes specifically required for the inheritance of RNAi would respond normally to direct exposure to oma-1 dsRNA but fail to inherit this silencing (Wan et al. 2018). zsp-1 mutants fail to respond immediately to direct exposure to oma-1 dsRNA, indicating that ZSP-1 is not specific to inheritance and, therefore, is generally required for RNAi (see also Fig. EV5B-D).",
    "ncbi_link": "oma-1: 177703
zsp-1: 171599
ZSP-1: 171599"
  },
  {
    "caption": "B. Kaplan-Meier curve represents the survival of BALB/c mice over time. Four BALB/c mice in each experimental group were infected i.v with 104 L. monocytogenes wild-type (EGD-e) or ΔinlK mutant.",
    "ncbi_link": "BALB/c: 
inlK: 985114///985114"
  },
  {
    "caption": "C. The L. monocytogenes EGD-e wild-type strain (WT), the ΔinlK mutant (ΔinlK) and the complemented strain (ΔinlK+pPL2 inlK) 104 CFU were inoculated i.v into BALB/c mice. Animals were euthanized 24 h, 48 h, 72 h or 96 h after infection and organs were recovered, homogenized, and homogenates serially plated on BHI. The number of bacteria able to colonize liver (left panel) and spleen (right panel) is expressed as log10 CFU. Four animals per bacterial strain, per time points and per experiment were used. Statistical analyses were performed on the results of 3 independent experiments using the Student t test. P values of <0.05 were considered statistically different and are labeled here as *.",
    "ncbi_link": "BALB/c: 
inlK: 985114"
  },
  {
    "caption": "B. Detection by immunofluorescence microscopy of InlK over-expressing in L. monocytogenes EGD-e (WT), ΔinlK, WT+pADc-inlK, ΔinlK+pPRT-inlK and the ΔsrtA mutant over-expressing inlK (ΔsrtA+pPRT-inlK) grown in BHI medium using the rabbit polyclonal anti-InlK antibody. InlK was detected at the surface of InlK over-expressing bacteria (WT+pADc-inlK and ΔinlK+pPRT-inlK), whereas it was undetectable at the surface WT bacteria or at the surface of the ΔstrA mutant over-expressing inlK.",
    "ncbi_link": "srtA: 986837
inlK: 985114"
  },
  {
    "caption": "C. Detection of InlK by Western blot on total lysates of L. monocytogenes EGD-e (WT), ΔinlK and ΔinlK+pPRT-inlK grown in BHI using the rabbit polyclonal anti-InlK antibody. Decreased concentrations of recombinant purified InlK were used as a positive control.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "D. Detection of secreted InlK in the supernatant of ΔsrtA mutants over-expressing InlK. Western blotting was carried out on trichloroacetic acid precipitates of ΔsrtA and ΔsrtA+pPRT-inlK culture (OD600 = 1) supernatants using the rabbit polyclonal anti-InlK antibody.",
    "ncbi_link": "srtA: 986837
inlK: 985114"
  },
  {
    "caption": "A. Bacterial pull-down of purified GST-MVP with the L. monocytogenes strains WT+pPRT-empty, ΔinlK+pPRT-empty, ΔinlK+pPRT-inlK and WT+pPRT-inlJ. GST-MVP bound to InlK over-expressing bacteria (ΔinlK+pPRT-inlK) but not to other bacteria. GST-ScarA was used as control of the specificity of the MVP precipitation by InlK over-expressing bacteria.",
    "ncbi_link": "inlJ: 
inlK: 985114"
  },
  {
    "caption": "B. Bacterial pull-down of MVP-GFP from transfected HeLa cell lysates with the L. monocytogenes strains WT+pPRT-empty, ΔinlK+pPRT-empty, ΔinlK+pPRT-inlK and WT+pPRT-inlJ. MVP-GFP bound to InlK over-expressing bacteria (ΔinlK+pPRT-inlK) but not to other bacteria.",
    "ncbi_link": "inlJ: 
inlK: 985114"
  },
  {
    "caption": "D. Detection of MVP recruitment at the surface of InlK over-expressing bacteria. HeLa cells were transfected with MVP-GFP (green), infected with L. monocytogenes EGD-e wild-type (WT), ΔinlK or ΔinlK+pPRT-inlK for 4 h, fixed for fluorescence light microscopy, and stained with anti-Listeria antibodies (red). Inset regions are magnified. The scale bar represents 1 µm.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "A. Detection of MVP recruitment at the surface of intracellular InlK over-expressing bacteria. HeLa cells were transfected with MVP-GFP (red), infected with InlK expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, fixed for fluorescence light microscopy. Intra- (only green) and extracellular (cyan = green+blue) bacteria were differentially stained with anti- Listeria antibody (cf Material and Methods). Inset regions are magnified. Arrows indicate another intracellular bacterium which recruit MVP-GFP. The scale bar represents 1 µm. The right panel represents the quantification of the intracellular bacteria that recruit MVP (mean%±SEM%) shown in the left panel. Statistical analyses were performed on the results of 3 independent experiments using the Student's t test. No significant difference was found between the 4 time points.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "B. Detection of MVP recruitment at the surface of intracytosolic InlK over-expressing bacteria. HeLa cells were transfected with MVP-tomato (red) and YFP-CBD (green), infected with InlK over-expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, fixed for fluorescence light microscopy and stained with phalloidin (blue). MVP positive bacteria were also labeled with YFP-CBD revealing that MVP was recruited by intracytosolic bacteria after the lysis of the internalization vacuole. Inset regions are magnified. The scale bar represents 1 µm.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "C. Kinetics of MVP and actin recruitment at the surface of InlK over-expressing bacteria. HeLa cells were transfected with MVP-tomato (red) and actin-GFP (green), infected with InlK over-expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, and prepared for real-time video microscopy. Image series were collected every 15 min for 2 h. The left part shows an MVP positive bacterium that never recruits actin. The right part shows MVP replacement by actin around the bacterium. No colocalization of MVP-Tomato and actin-GFP was detected. Time is indicated along the Y axis. The entire image sequence can be viewed as Video S1.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "A. Impaired recruitment of p62 to MVP positive Listeria. HeLa cells were transfected with MVP-GFP (green), infected with InlK over-expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, fixed for fluorescence light microscopy, and stained with phalloidin (blue) and anti-p62 antibody (red). Inset regions are magnified. Arrows indicate independent bacteria The scale bar represents 1 µm. The vast majority of MVP-positive bacteria were completely devoid of anti-p62 labeling (95.1±2.0%; mean ± SEM from n = 3 experiments) but 4.9±2.0% (mean ± SEM from n = 3 experiments) were stained at one pole with MVP and at the other pole with p62.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "B. Impaired recruitment of GFP-LC3 on MVP positive Listeria. HeLa cells were transfected with MVP-tomato (red) and GFP-LC3 (green), infected with InlK over-expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, fixed for fluorescence light microscopy, and stained with phalloidin (blue). Inset regions are magnified. The scale bar represents 1 µm. MVP and/or actin positive bacteria were never recognized by GFP-LC3. Arrows point to bacteria at different steps of the infection process: 1) InlK over-expressing bacterium is totally covered by MVP; 2) bacterium is partially labeled with MVP (at the poles) and actin (at the center); 3) bacterium is completely covered by actin; 4) bacterium is enclosed in an GFP-LC3 positive autophagosome.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "C. Kinetics of autophagy escape for MVP positive Listeria. Jeg3 cells were transfected with MVP-tomato (red) and GFP-LC3 (green), infected with InlK over-expressing Listeria (ΔinlK+pPRT-inlK) for 4 h, and prepared for real-time video microscopy. Image series were collected every 5 min for 2 h. Time is indicated along the Y axis. The left panel shows that the GFP-LC3 membranous aggregate detaches from the MVP positive Listeria. The entire image sequence can be viewed as Video S2. The right panel shows that the GFP-LC3 membranous aggregate on MVP positive bacteria does not lead to an autophagosome formation, whereas those bacteria efficiently divided. The entire image sequence can be viewed as Video S3.",
    "ncbi_link": "inlK: 985114"
  },
  {
    "caption": "D. Impaired recruitment of GFP-LC3 and ubiquitin to MVP positive ΔactA Listeria. HeLa cells were transfected with MVP-tomato (red) and GFP-LC3 (green), infected with InlK over-expressing ΔactA (ΔactA+pADc-inlK) for 4 h, fixed for fluorescence light microscopy, and stained with anti-ubiquitin antibody (blue) and DAPI (white). Inset regions are magnified. The scale bar represents 1 µm.",
    "ncbi_link": "actA: 987035
inlK: 985114"
  },
  {
    "caption": "E. LC3 levels in infected RAW 267.4 macrophages. Left panel: RAW 267.4 macrophages were infected with L. monocytogenes EGD (WT), ΔactA or ΔactA+InlK for 6 h. Cell total lysates were immunobloted for LC3 and actin. Western blot is representative from 3 independent experiments. Right panel: Quantification of the relative LC3-II level (mean ± SEM) shown in the left panel. Statistical analyses were performed on the results of 3 independent experiments using the Student's t test. P values of <0.05 were considered statistically different.",
    "ncbi_link": "actA: 987035
InlK: 985114"
  },
  {
    "caption": "A. InlK and ActA expression in Listeria strains used for survival assays. Total lysates of L. monocytogenes EGD-(pADc-GFP), EGD-(pADc-inlK), ΔactA-(pADc-GFP) and ΔactA-(pADc-inlK) grown in BHI were immunoblotted using anti-ActA and anti-InlK antibodies.",
    "ncbi_link": "actA: 987035
inlK: 985114"
  },
  {
    "caption": "B. Intracellular survival of EGD-(pADc-GFP), EGD-(pADc-inlK), ΔactA-(pADc-GFP) and ΔactA-(pADc-inlK) in RAW 267.4 macrophages. Statistical analyses were performed on the results of 3 independent experiments using the Student t test. P values of <0.05 were considered statistically different and are labeled here as *.",
    "ncbi_link": "actA: 987035
inlK: 985114"
  },
  {
    "caption": "C. Intracellular survival of ΔactA-(pADc-GFP) and ΔactA-(pADc-inlK) in MVP-GFP transfected Jeg3 cells. Statistical analyses were performed on the results of 3 independent experiments using the Student's t test. P values of <0.05 were considered statistically different and are labeled here as *.",
    "ncbi_link": "actA: 987035
inlK: 985114
MVP: 9961"
  },
  {
    "caption": "D. Intracellular survival of ΔactA-(pADc-GFP) and ΔactA-(pADc-inlK) in MVP-GFP transfected HeLa cells. Statistical analyses were performed on the results of 3 independent experiments using the Student's t test. P values of <0.05 were considered statistically different and are labeled here as *.",
    "ncbi_link": "actA: 987035
inlK: 985114
MVP: 9961"
  },
  {
    "caption": "E. MVP levels in RAW 267.4 macrophages treated with MVP-siRNA. Western blot is representative from 3 independent experiments.",
    "ncbi_link": "MVP: 9961"
  },
  {
    "caption": "F. Intracellular survival of ΔactA-(pADc-GFP) and ΔactA-(pADc-inlK) in MVP knock-down RAW 267.4 macrophages. Statistical analyses were performed on the results of 3 independent experiments using the Student t test. P values of <0.05 were considered statistically different and are labeled here as *.",
    "ncbi_link": "actA: 987035
inlK: 985114
MVP: 9961"
  },
  {
    "caption": " A. GAR domain deletion or mutation perturbs binding to Kif5a. Co-immunoprecipitation analysis of Kif5a and HA-Dendra2-tagged nucleolin (both overexpressed in HEK-293 cells). IP was performed with HA antibody and probed in Western blot with anti-Kif5a and anti-HA antibodies. Ncl FL - HA -Dendra2- full length nucleolin; Ncl ΔGAR - HA-Dendra2- nucleolin with a GAR domain deletion; Ncl GAR(N) - HA-Dendra2- nucleolin with all 10 arginines in the GAR domain mutated to asparagines; DEN - Dendra2. Note that HA input blots for HA-Dendra2 (Dendra) and the other three constructs are from the same membrane, but shown discontinuously owing to the different migration of these proteins in PAGE. B. Quantification of (A). n = 3 independent biological repeats; means ± SEM; **** p < 0.0001, ANOVA with Tukey's post-test.",
    "ncbi_link": "DEN: 
Dendra: 
Dendra2: 
HA: 
Ncl: 4691
nucleolin: 4691"
  },
  {
    "caption": " G. HEK-293 cells were transfected with plasmids expressing HA-Dendra2- full length nucleolin (Ncl FL), HA-Dendra2-nucleolin with a GAR domain deletion (Ncl ΔGAR) or HA-Dendra2-nucleolin with all 10 arginines in the GAR domain mutated to asparagines (Ncl GAR(N)) and processed as in (F). H. Quantification of (G). Levels of nucleolin in pulldowns were normalized to input levels and expressed as % relative to full-length HA-Dendra2-nucleolin. n = 4 independent biological repeats; means ± SEM; **** p<0.0001, ANOVA with Dunnett's post-test.",
    "ncbi_link": "Dendra2: 
HA: 
Ncl: 4691
nucleolin: 4691"
  },
  {
    "caption": " A. GAR deletion in nucleolin reduces partitioning to nucleoli in adult DRG neurons, transduced with the peripheral neuron specific AAV-PHP.S vector expressing full length HA-Dendra2-nucleolin (Ncl FL) or respective ΔGAR mutant (Ncl ΔGAR) upon seeding and analyzed by epifluorescence microscopy 9-10 days later. Shown are representative Dendra2 fluorescence images collected from the non-activated (green) emission line. Hoechst 33342 (10 µM) was used to outline nuclei. Superimposed phase contrast and Dendra2 fluorescence images are shown on the right. Scale bar - 25 µm. B. Quantification of the nucleolar/nuclear intensity ratios in DRG cells shown in (A). n = 38-54 cells per sample in 3 independent biological repeats; means ± SEM; **** p<0.0001, Mann-Whitney test ",
    "ncbi_link": "Dendra2: 
HA: 
Ncl: 17975
nucleolin: 17975"
  },
  {
    "caption": " C. Time-lapse live imaging of nuclei in DRG neurons transduced with AAV-PHP.S HA-Dendra2-nucleolin (full length and ΔGAR mutant), after a hypotonic challenge with double-distilled water (ddH20). Shown are epifluorescence images (Dendra2 green emission line) taken at indicated times after medium replacement with ddH20. Scale bar - 10 µm. D. Quantification of nucleolar Dendra2 signal in (C) with intensity values immediately before medium replacement set as 100%. n = 17-24 cells per sample in 3 biological repeats; means ± SEM; Two-way ANOVA with Sidák's post-test detected a significant time-dependent reduction of nucleolar signal (p < 0.0001) and no difference between full length and ΔGAR mutant nucleolin (p > 0.05) ",
    "ncbi_link": "Dendra2: 
HA: 
nucleolin: 17975"
  },
  {
    "caption": " B. Western blot analysis of nucleolin in DRG neurons from wildtype (WT) and GAR+/- mice cultured in Boyden chambers. Tuj1 was used as a loading control. The higher nucleolin band in GAR+/- corresponds to WT nucleolin and lower band to nucleolin with a 41 aa deletion (corresponding to about 4 kDa reduction in protein size). C. Quantification of (B), total nucleolin levels (sum of both bands where applicable) were normalized to Tuj1 and expressed as GAR+/- / WT ratios. n = 3 independent biological repeats; means ± SEM; * p < 0.05, 1 sample t-test. ",
    "ncbi_link": "nucleolin: 17975"
  },
  {
    "caption": " A, B. Representative maximum projections of exposure matched confocal images of immunofluorescence for nucleolin and neurofilament (NF) and the neuronal marker Tuj1 in sciatic nerve axons from WT and GAR+/- mice shown in (A). Upper panels show total nucleolin stain. Middle panels show merged image of nucleolin (gray), NF and Tuj1 (magenta), and DAPI (blue). Lower panels show nucleolin overlaps with NF and Tuj1 signals as the "axon only" signal. B shows quantification of nucleolin immunofluorescence with approximately a 50% reduction in nucleolin in the axons of GAR+/- mice in vivo. n = 3 WT, n = 4 GAR+/-; means ± SEM; * p < 0.05, unpaired Student's t-test. Scale bar - 10 µm. ",
    "ncbi_link": "nucleolin: 17975"
  },
  {
    "caption": " C-F. Representative, exposure matched maximum projection confocal images of FISH for Kpnb1 (C) or mTOR (E) mRNA and NF plus Tuj1 immunostaining from sciatic nerve sections from WT (left) or GAR+/- mice. Upper panels for each show total mRNA signal. Middle panels show mRNA (gray) signals merged with NF plus Tuj1 (magenta) and DAPI (blue). Lower panels show mRNA signal that overlap with NF plus Tuj1 signal (labeled \"axon only\" signal). Quantification of axonal Kpnb1 (D) and mTOR (F) mRNA signals compared to the negative control, DapB mRNA, show a significant reduction in these axonal mRNAs in the GAR+/- mice. n = 3 WT, n = 3 GAR+/-; means ± SEM; ** p < 0.01, *** p < 0.001, ****p < 0.0001 unpaired Student's t-test. Scale bar - 10 µm. ",
    "ncbi_link": "DapB: 939024
Kpnb1: 16211
mTOR: 56717"
  },
  {
    "caption": " D. Representative images for FISH analysis of Inpp5f in DRG neurons treated for 48h with 10 µM AS1411 or 10 µM control aptamer, replated and grown for 18h. FISH signal is shown in gray, cell somata (left) and axons (right) are visualized by neurofilament immunostaining (magenta). Scr - scrambled FISH probe served as a negative control. Scale bar - 10 µm. ",
    "ncbi_link": "Inpp5f: 101490"
  },
  {
    "caption": " A, B. Representative exposure-matched FISH/IF images for DRG neurons co-transfected with control vs. nucleolin (Ncl) siRNA plus siRNA-resistant wild type (WT; A) or ∆GAR (B) Ncl cDNAs. Axonal Kpnb1 mRNA is decreased with the Ncl knockdown, and this is not rescued by expression of ∆GAR Ncl mutant (scale bars - 10 µm). ",
    "ncbi_link": "Kpnb1: 16211
Ncl: 17975
nucleolin: 17975"
  },
  {
    "caption": " A. Cultured DRG neurons from wild type (WT) Thy1-YFP mice and Thy1-YFP / GAR+/- mice (YFP signal is shown in green). Cells were imaged every hour for a period of 48 h. Scale bar - 100 μm. B. Quantification of the time-lapse imaging experiment shown in (A). Growth rate of the longest neurite of each cell was calculated from the time point of starting growth. n = 4 independent biological repeats; means ± SEM, **** p < 0.0001, two-way ANOVA. ",
    "ncbi_link": "YFP: 
Thy1: 21838"
  },
  {
    "caption": " C. Fluorescence images of cultured DRG neurons from adult C57BL/6 mice infected with AAV-PHP.s expressing HA-Dendra fused with the wild type nucleolin GAR domain (GAR WT) or with the GAR domain with all 10 arginines substituted with asparagines, GAR(N). Neurons were re-plated 9-10 days after AAV infection. 24h after re-plating cells were fixed and stained with anti-HA (grey) and anti-NFH (magenta) antibodies. Scale bar - 100 μm. D. Quantification of total axonal outgrowth and mean process length in HA-positive cells in (C). Outgrowth measurements were based on NFH staining. n = 6 independent biological repeats; means ± SEM; * p < 0.05, *** p < 0.001 (Student's-test). ",
    "ncbi_link": "Dendra: 
HA: 
nucleolin: 17975"
  },
  {
    "caption": "D Western blot  of Sec63, mCherry and Pgk1 from WT cells (SSY1404), cells harboring the estradiol-inducible system (SSY1405) or ∆opi1  cells (SSY1607), all of which expressed Sec63-mNeon and Rtn1-mCherry. Cells were untreated or treated with 800 nM estradiol  for 6 h. Pgk1 served as a loading control.",
    "ncbi_link": "opi1: 856366"
  },
  {
    "caption": "E Quantification of ER size in estradiol-treated cells harboring the inducible system (SSY1405), untreated ∆opi1  cells (SSY1607) and WT cells (SSY1404) treated with 8 mM DTT for 1 h. Bars represent mean + s.e.m., n = 3 biological replicates. Asterisks indicate statistical significance compared with 0 nM estradiol or ∆opi1 cells, as judged by a two-tailed Student's t-test assuming equal variance. *, P < 0.05; **, P < 0.01; n.s., not significant.",
    "ncbi_link": "opi1: 856366"
  },
  {
    "caption": "C Sec63-mNeon and Rtn1-mCherry images of ∆lnp1  and ∆sey1 cells harboring the inducible system and treated with 800 nM estradiol for 6 h.",
    "ncbi_link": "lnp1: 856599
sey1: 854336"
  },
  {
    "caption": "C Quantification of peripheral  ER  structures in WT and ∆ice2  cells harboring the inducible system (SSY1405, 1603) and treated with 800 nM estradiol for the  times indicated. Bars are the mean percentage of cell cortex  covered by tubules  (purple) or  sheets (green), n = 3 biological replicates. Upper error bars are s.e.m. for the sum of  tubules  and sheets, lower error bars are s.e.m. for sheets. Asterisks indicate statistical significance compared with the corresponding value in WT cells, as judged by a two-tailed Student's t-test assuming equal variance. **, P < 0.01; n.s., not significant.",
    "ncbi_link": "ice2: 854718"
  },
  {
    "caption": "E Quantification of peripheral ER structures in untreated WT, Δice2, Δopi1 and Δice2 Δopi1 cells (SSY1404, 2356, 2595, 2811). Bars are the mean percentage of cell cortex  covered by tubules (purple) or sheets (green), n = 3 biological replicates. Upper error bars are s.e.m. for the sum of tubules  and sheets, lower error bars are s.e.m. for sheets. Asterisks indicate statistical significance compared with the corresponding value in WT cells, as judged by a two-tailed Student's t-test assuming equal variance. **, P < 0.01; n.s., not significant.",
    "ncbi_link": "ice2: 854718
opi1: 856366"
  },
  {
    "caption": "C, D Fluorescence  images of  cortical  sections of WT and Δice2 cells expressing Sec63-mNeon  and  Rtn1-mCherry (SSY1405, 1603) that were untreated (C) or treated with 8 mM DTT for 1 h (D).",
    "ncbi_link": "ice2: 854718"
  },
  {
    "caption": "B Growth assays of untreated WT, Δice2, Δnem1, Δnem1 Δice2, Δspo7, Δspo7 Δice2, Δpah1 and Δpah1 Δice2  cells (SSY1404, 2356, 2482, 2484, 2481, 2483, 2807, 2808). Numbers represent areas under the curves and serve as growth indices. Mean + s.e.m., n = 3 biological replicates. Data for WT and ∆ice2  cells are the same in the left and middle panels.",
    "ncbi_link": "ice2: 854718
nem1: 856393
pah1: 855201
spo7: 851224"
  },
  {
    "caption": "C, D  Lipidomic analysis  of WT, Δice2, Δnem1, Δice2 Δnem1, Δspo7 and Δice2 Δspo7 cells (SSY1404, 2356, 2482, 2484, 2481, 2483). Mean + s.e.m., n = 4 biological replicates. Asterisks indicate statistical significance compared with WT cells, as judged by a two-tailed Student's t-test assuming equal variance. *, P < 0.05; **, P < 0.01. Data for WT and Δice2 cells are the same as in both panels.",
    "ncbi_link": "ice2: 854718
nem1: 856393
spo7: 851224"
  },
  {
    "caption": "E Sec63-mNeon images of untreated WT, Δnem1, Δnem1Δice2, Δspo7 and Δspo7  Δice2 cells (SSY1404, 2482, 2484, 2481, 2483).",
    "ncbi_link": "ice2: 854718
nem1: 856393
spo7: 851224"
  },
  {
    "caption": "D Western blot of  HA from Pah1 dephosphorylation reactions that contained  phosphorylated Pah1-HA  from ∆nem1 mutants (SSY3065) and microsomes  from cells of the indicated genotypes (SSY3053, 3074, 3075, 3095). Phosphorylated Pah1  and dephosphorylated Pah1 resulting from treatment with recombinant  alkaline phosphatase (PPase) are shown for reference.",
    "ncbi_link": "nem1: 856393"
  },
  {
    "caption": "E Western blot  of  HA, Sec61  and Pgk1  from cell lysates and microsomes prepared from WT and ∆ice2 cells expressing Nem1-HA  (SSY3140, 3141). Nem1 is undetectable in cell lysates due to its low abundance.",
    "ncbi_link": "ice2: 854718"
  },
  {
    "caption": "Western blots of  FLAG,  HA  and Dpm1  from cell lysates or anti-FLAG immunoprecipitates  of WT or ∆nem1 cells containing Spo7-FLAG, Nem1-FLAG  or Ice2-HA as indicated (SSY122, 2421, 3183, 3184, 3195, 3196, 3197). The asterisk marks the position of the light chain from the antibody used for  immunoprecipitation. The diamond marks a protein that is non-specifically precipitated by the anti-FLAG antibody.  IP, immunoprecipitate.",
    "ncbi_link": "FLAG: 
HA: 
Ice2: 854718
nem1: 856393
Nem1: 856393
Spo7: 851224"
  },
  {
    "caption": "E Images of cells with endogenously tagged  Ice2-mScarlet  and Spo7-mNeon or Nem1-mNeon (SSY3244, 3245). Arrows indicate foci containg both Ice2 and either Spo7 or Nem1. F Quantification of Spo7 and Nem1 foci in WT and ∆ice2 cells (SSY2916, 3238, 2917, 3239). Mean + s.e.m., n = 3 biological replicates. Asterisks indicate statistical significance compared with the respective WT cells, as judged by a two-tailed Student's t-test assuming equal variance. **, P < 0.01. ",
    "ncbi_link": "ice2: 854718"
  },
  {
    "caption": "A Lipidomic analysis of WT and ∆ice2  cells in which PAH1 was replaced with PAH1-HA or pah1(7A)-HA as indicated (SSY2841, SSY2842, SSY2970). Mean + s.e.m., n = 4 biological replicates. Asterisks indicate statistical significance compared with WT cells, as judged by a two-tailed Student's t-test assuming equal variance. **, P < 0.01.",
    "ncbi_link": "HA: 
ice2: 854718
PAH1: 855201
pah1: 855201"
  },
  {
    "caption": "A Sec63-mNeon images of  mid   and cortical  sections of untreated WT and ∆opi1 cells, overexpressing ICE2  where indicated (SSY1404, 2588, 2595, 2596).",
    "ncbi_link": "ICE2: 854718
opi1: 856366"
  },
  {
    "caption": "D  Growth assays on solid media of WT, ∆hac1, Δice2, and Δhac1 Δice2  cells (SSY1404, 2356, 2805, 2806) in the absence or presence of 0.2 µg/ml tunicamycin. For each series, cells were diluted fivefold from one step to the next.",
    "ncbi_link": "hac1: 850513
ice2: 854718"
  },
  {
    "caption": "Multiple tissue (eye, brain, adrenal gland, submandibular gland, oesophagus, lung, heart, liver, kidney, spleen, pancreas, stomach, duodenum, jejunum, ileum, caecum, colon, spinal cord, dorsal root ganglia, skeletal muscle, testis, epididymis, female gonad, skull) northern blot for CAVII. In the P56 mouse, CAVII is prominently expressed in the central nervous system including brain and spinal cord. Gapdh served as the loading control.",
    "ncbi_link": "CAVII: 12354
Gapdh: 407972"
  },
  {
    "caption": "(C) Developmental profile of CAVII protein expression. Western blot analysis of protein lysates of whole hippocampus shows increasing CAVII levels from P3 to P30. The band of the appropriate size (∼30 kDa) was absent in protein lysates from Car7 KO tissue.beta Actin served as the loading control in C and D.",
    "ncbi_link": "Car7: 12354"
  },
  {
    "caption": "(D) In western blots from protein lysates of cultured cells, CAVII was detected in mixed glial/neuron cultures but not in glia cell cultures. The presence of astrocytes in all cultures was confirmed by detection of GFAP. Actin served as the loading control in C and D.",
    "ncbi_link": "CAVII: 12354"
  },
  {
    "caption": "Original single-cell pHi traces and their time derivatives from P5 and P14 WT and P14 CA VII KO neurons (baseline pHi 7.21, 7.13 and 7.11, respectively). Superfusion with CO2/HCO3−-free HEPES solution (upper horizontal bars) evoked an intracellular alkalinization, which in P14 WT was large and suppressed by 100 μM acetazolamide (AZ, lower horizontal bar), indicating the presence of CA activity (see Supplementary Materials and methods). The possible effect of AZ on extracellular CAs was excluded by adding 10 μM benzolamide (a poorly permeant CA inhibitor). Inset shows an overlay of the BCECF fluorescence signal and Dodt gradient contrast image of CA1 pyramidal neurons in P14 WT (scale bar 10 μm).",
    "ncbi_link": "CA: 12354"
  },
  {
    "caption": "Summary of the results obtained using the cytosolic CA activity detection method shown in A and quantified as the percentage of cells showing cytosolic CA activity. Data from CA II KO and CA II/VII KO neurons were obtained only at >P35. The number of cells tested is indicated for each bar. The animal numbers for WT mice at the different age points was n=3 (P5-8), n=2 (P10-11), n=3 (P14-16), n=2 (P17-18), n=2 (P20-30) and n=2 (>P35); for CAVII KO mice the numbers were n=3 (P5-8), n=2 (P10-11), n=5 (P14-16), n=3 (P17-18), n=4 (P20-30) and n=2 (>P35); and for CA II KO and CA II/CAVII KO mice the number was n=2 (>P35).",
    "ncbi_link": "CA II: 12349
CAVII: 12354
VII: 12354"
  },
  {
    "caption": "Typical single pyramidal neuron pHi responses evoked by withdrawal of CO2/HCO3− (horizontal bar, HEPES) in slices from >P35 WT, CAVII KO and CA II/VII KO mice. The rate of rise and the amplitude of the alkaline shift are identical in WT (P39, baseline pHi 7.01) and CAVII KO neurons (P40, 7.06), whereas alkalinization develops much more slowly in the CA II/VII KO (P46, 7.04)",
    "ncbi_link": "CA II: 12349
CAVII: 12354
VII: 12354"
  },
  {
    "caption": "Excitatory GABAergic response in WT, but not in CAVII KO neurons. Picrotoxin blocked the biphasic response (PiTX 90 μM; n=3/genotype). The mean initial slope of the depolarizing shift was faster in WT than in CAVII KO (13.53±1.27 versus 6.39±0.96 mV/s, P<0.001, Student's t-test). The resting membrane potential of WT and CAVII KO neurons did not differ (−71.0±1.1 versus −72.3±1.4 mV, respectively; n=15 neurons for both genotypes, P=0.47, Student's t-test). *P<0.05, **P<0.01 and ***P<0.001. Error bars denote s.e.m. and n is the number of slices (C) or cells tested (one cell per slice) (A, B and D)",
    "ncbi_link": "CAVII: 12354"
  },
  {
    "caption": "Microinjection of GABA (5 mM for 100 ms, sr/slm border in the presence of CGP55845/TTX, arrowheads) induced a pronounced depolarization in WT neurons (black) that was abolished in the absence of CO2/HCO3− (grey). The depolarization was smaller in CA VII KO (red). Bar diagram illustrates GABAergic mean peak depolarization in P12-16 WT and CAVII KO (13.3±0.5 versus 8.3±0.6 mV, P<0.001, Student's t-test). *P<0.05, **P<0.01 and ***P<0.001. Error bars denote s.e.m. and n is the number of slices (C) or cells tested (one cell per slice) (A, B and D).",
    "ncbi_link": "CA VII: 12354
CAVII: 12354"
  },
  {
    "caption": "In the presence of AP5/CNQX/CGP55845, microinjection of GABA (5 mM, sr/slm border) triggered SR 95531-sensitive field potential spikes in WT slices already upon 8-ms injection, while even 16-ms injection evoked hardly any spikes in CAVII KO (left). Mean number of spikes was plotted against GABA puff duration in P12-16 WT and CAVII KO (P<0.01 and P<0.001, Student's t-test; right). *P<0.05, **P<0.01 and ***P<0.001. Error bars denote s.e.m. and n is the number of slices (C) or cells tested (one cell per slice) (A, B and D)",
    "ncbi_link": "CAVII: 12354"
  },
  {
    "caption": "After P35, depolarizations upon GABA microinjection (arrowheads) in the presence of CGP55845/TTX were indistinguishable in WT (black), CA VII KO (red) and CA II KO (blue) but smaller in CA II/VII KO (green). The depolarization in WT was abolished in the absence of CO2/HCO3− (grey, n=5). Bar diagram summarizes mean peak depolarization for each genotype (right; ANOVA, Bonferroni). *P<0.05, **P<0.01 and ***P<0.001. Error bars denote s.e.m. and n is the number of slices (C) or cells tested (one cell per slice) (A, B and D)",
    "ncbi_link": "CA II: 12349
CA VII: 12354
VII: 12354"
  },
  {
    "caption": "Representative raw traces of epidural EEG recordings during hyperthermia (HT) from a WT and a CA VII KO mouse. Seizures were reliably induced in WT (n=9) but not in CA VII KO (n=7). Error bars denote s.e.m., all P-values are based on Student's t-test (***P<0.001), and animal number is given in bar diagrams. Rectal temperatures are given above the traces.",
    "ncbi_link": "CA VII: 12354
VII: 12354"
  },
  {
    "caption": "Specimen recordings of breath rate from a WT and a CA VII KO mouse. The baseline breath rate (WT 153±11 breaths/min and CA VII KO 157±8 breaths/min) was increased during HT in both genotypes (WT 272±28 breaths/min and CA VII KO 279±12 breaths/min). The bar diagram summarizes the mean increase in breath rate in WT (177±12%) and CA VII KO mice (178±6%, P=0.98).Error bars denote s.e.m., all P-values are based on Student's t-test (***P<0.001), and animal number is given in bar diagrams. Rectal temperatures are given above the traces.",
    "ncbi_link": "CA VII: 12354"
  },
  {
    "caption": "Hyperthermia caused a comparable alkalosis in blood pH in both WT and CA VII KO mice. The blood pH did not differ between the two genotypes under control conditions (P=0.37) or during HT (P=0.44). Error bars denote s.e.m., all P-values are based on Student's t-test (***P<0.001), and animal number is given in bar diagrams. Rectal temperatures are given above the traces.",
    "ncbi_link": "CA VII: 12354"
  },
  {
    "caption": "CA VII expression during human brain development. Line plots show the log2-transformed exon array signal intensity in the neocortex (NCX) and hippocampal formation (HIP) from the early fetal period to late adulthood. The solid line between periods 7 and 8 separates the prenatal from the postnatal period.",
    "ncbi_link": "CA VII: 12354"
  },
  {
    "caption": "CA VII expression during human brain development. Line plots show the log. Line plots show the normalized ratio of absolute copy number of CA VII to Gapdh by droplet digital PCR (ddPCR, right) in the neocortex (NCX) and hippocampus (HIP) from the early fetal period to late adulthood. The solid line between periods 7 and 8 separates the prenatal from the postnatal period.",
    "ncbi_link": "CA VII: 12354
Gapdh: 407972"
  },
  {
    "caption": "(B) Quantification by micro-CT of mean tumor volumes in KP mice derived from 50 randomly-selected tumors at 8, 12, 16, and 20 weeks post-infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 (n = 18 mice, 21 mice, 21 mice, and 20 mice, respectively).",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(C) Quantification by micro-CT of total tumor volume per mouse in KP mice after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 at 8, 12, 16, and 20 weeks post-infection.",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(D) Depictions and quantitation of total tumor burden (total tumor area/total lung area) in KP mice after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 at 21 weeks after infection. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(E) Distribution of histological tumor grades in KP mice after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 (n = 50 tumors each) at 21 weeks after infection. For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(F) Assessment of the mitotic index of tumor cells by phosphorylated-histone H3 (pHH3)-positive nuclei density in KP mice LUAD tumors at 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3 (n = 50 tumors each). For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(G) Nf1 mRNA expression in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1: 18015
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(H) Representative hematoxylin and eosin (H&E) and p-Fak1 immunohistochemical (IHC) staining of LUAD tumor sections 21 weeks after infection with control sgTom (grade 1 depicted), sgNf1.1 (grade 3 depicted), sgNf1.2 (grade 3 depicted), or sgNf1.3 (grade 3 depicted) (n = 50 tumors each). H&E scale bars (low-magnification top row = 100 μm, high-magnification bottom row = 250 μm); p-Fak1 IHC scale bars (low-magnification top row = 250 μm, high-magnification bottom row = 500 μm).",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(I) Quantification of p-Fak1 IHC signals in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015"
  },
  {
    "caption": "(J) Quantification of p-Fak1 IHC signals in sgNf1.3 LUAD tumor sections analyzed by tumor grade. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Nf1.3: 18015"
  },
  {
    "caption": "(K) Quantification of Psat1 mRNA expression in LUAD tumor sections 21 weeks after infection with control sgTom, sgNf1.1, sgNf1.2, or sgNf1.3. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.1: 18015
Nf1.2: 18015
Nf1.3: 18015
Psat1: 107272"
  },
  {
    "caption": "(L) Quantification of Psat1 mRNA expression in sgNf1.3 LUAD tumor sections analyzed by tumor grade. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Nf1.3: 18015
Psat1: 107272"
  },
  {
    "caption": "(A) Western blotting analysis of p53 expression in various p53/TP53-WT cell lines incubated with the DNA-intercalating agent doxorubicin (DOXO, 0.2 µg/ml for 6 hours) to induce p53 stabilization (n = 3 biological replicates).",
    "ncbi_link": "TP53: 7157
p53: 22059"
  },
  {
    "caption": "(B, C) Western blotting analysis confirming NF1 upregulation and p-FAK1 downregulation in (B) DOXO-treated PDKN1 cells and (C) DOXO-treated PDKN2 cells transduced with PGK-NF1 (n = 3 biological replicates).",
    "ncbi_link": "NF1: 4763
PGK: 5230"
  },
  {
    "caption": "(D) Western blotting analysis confirming NF1 downregulation and p-FAK1 upregulation in DOXO-treated SW1573 cells transduced with sgNf1.3 (n = 3 biological replicates).",
    "ncbi_link": "Nf1.3: 4763"
  },
  {
    "caption": "(E, F) Western blotting analysis confirming Nf1 downregulation and p-Fak1 upregulation in (E) DOXO-treated LKR10 and (F) DOXO-treated LKR13 clones transduced with sgNf1.3 (n = 3 biological replicates).",
    "ncbi_link": "Nf1.3: 18015"
  },
  {
    "caption": "(G) FAK1 target gene expression in DOXO-treated PDKN1 cells transduced with PGK-control or PGK-NF1 (n = 3 biological replicates). For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "NF1: 4763
PGK: 5230
FAK1: 5747"
  },
  {
    "caption": "(H, I) Subcutaneous tumor volumes of DOXO-treated PDKN1 and PDKN2 cells transduced with PGK-control or PGK-NF1 (n=18 each).",
    "ncbi_link": "NF1: 4763
PGK: 5230"
  },
  {
    "caption": "(J-L) Subcutaneous tumor volumes of (J) SW1573, (K) LKR10, and (L) LKR13 cells transfected with sgTom or sgNf1.3 (n=18 each).",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "(M) Depictions and quantitation of KrasG12D/+; p53+/+ (K-only) autochthonous tumor burden (total tumor area/total lung area) in pSECC-sgTom (n = 18 mice) or pSECC-sgNf1.3 mice (n = 21 mice). For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Kras: 16653
Nf1.3: 18015
p53: 22059"
  },
  {
    "caption": "(N) Analysis of tumor grades in K-only autochthonous tumors derived from pSECC-sgTom (n = 18 mice) or pSECC-sgNf1.3 mice (n = 21 mice). For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "(O) Quantification of Ki-67-positive nuclei per mm2 in K-only autochthonous tumors derived from pSECC-sgTom (n = 18 mice) or pSECC-sgNf1.3 mice (n = 21 mice). For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "(A) Glucose consumption and lactate excretion in KP and KPΔNF1 clones normalized by cell count (n = 4 biological replicates). For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(B) Glutamine consumption in KP and KPΔNF1 clones normalized by cell count (n = 4 biological replicates). For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(C) Relative viability of KP and KPΔNF1 cells after 72 h of GPNA treatment assayed by cell-titer glo (relative luminescent units) (n = 4 biological replicates).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(D) Cumulative population doublings of KP and KPΔNF1 cells cultured with 2.0 or 0.5 mM glutamine (n = 4 biological replicates).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(E) Two patient-derived KRAS;NF1-mutant LUAD cell lines (PDKN1, PDKN2), as well as the control patient-derived KRAS-mutant/NF1-WT LUAD cell line (PDK), were passaged for 14 population doublings prior to collection. The heatmap displays the most significantly upregulated genes in the PDKN1 and PDKN2 cell lines (relative to the PDK control), with the degree of upregulation depicted by color as indicated in the legend.",
    "ncbi_link": "KRAS: 3845
NF1: 4763"
  },
  {
    "caption": "(H) Western blotting analysis of Psat1 expression in KP and KPΔNF1 cells infected with sgTom or sgPsat1 following selection. GAPDH was used as a loading control.",
    "ncbi_link": "Tom: 
NF1: 18015
Psat1: 107272"
  },
  {
    "caption": "(I) Cumulative population doublings of KP and KPΔNF1 cells after transduction with sgTom- or sgPsat1-containing vectors (n = 4 biological replicates).",
    "ncbi_link": "Tom: 
NF1: 18015
Psat1: 107272"
  },
  {
    "caption": "(J-L) Cumulative population doublings of patient-derived KRAS-mutant LUAD cell lines that are either (J, K) NF1-mutant (PDKN1 and PDKN2) or (L) NF1-WT (PDK) after selection with sgTom- or sgPsat1-containing vectors (n = 4 biological replicates).",
    "ncbi_link": "Tom: 
KRAS: 3845
NF1: 4763
Psat1: 29968"
  },
  {
    "caption": "Relative viability of KP and KPΔNF1 clones after CB-839 treatment (IC50: 18 nM) for 72 h assayed via CellTiter-Glo (relative luminescence units). All data points are relative to vehicle-treated controls (n = 4 biological replicates).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "Relative viability of KP and KPΔNF1 clones after AOA treatment (IC50: 6 µM) for 72 h assayed via CellTiter-Glo (relative luminescence units). All data points are relative to vehicle-treated controls (n = 4 biological replicates).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(D) Cumulative population doublings of KP and KPΔNF1 cells incubated with vehicle, 18 nM CB-839, or 6 µM AOA after 6 d in culture (n = 4 biological replicates). For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "(E) Relative viability of the indicated human KRAS-mutant lung cancer cell lines by trypan blue exclusion assay. Cells were incubated with vehicle, 18 nM CB-839, or 6 µM AOA for 72 h (n = 4 biological replicates). All data points are normalized to vehicle-treated cell lines. For bar charts, data presented as means with error bars representing standard deviations (SDs).",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": "Quantification by micro-CT of mean tumor volumes in (B) CB-839-, or vehicle-treated KP mice derived from 50 randomly-selected tumors at 8, 12, 16, and 20 weeks post-infection with control sgTom or sgNf1.3 (n = 21 mice and 21 mice, respectively). Vehicle-treated KP mice are the same control group for (B)",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "Quantification by micro-CT of mean tumor volumes in (C) AOA-, or vehicle-treated KP mice derived from 50 randomly-selected tumors at 8, 12, 16, and 20 weeks post-infection with control sgTom or sgNf1.3 (n = 21 mice and 21 mice, respectively). Vehicle-treated KP mice are the same control group for (C).",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "Quantification by micro-CT of total tumor volume per mouse in (D) CB-839-, or vehicle-treated KP mice after infection with control sgTom or sgNf1.3 at 8, 12, 16, and 20 weeks post-infection. Vehicle-treated KP mice are the same control group for (D)",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "E) Quantification by micro-CT of total tumor volume per mouse in , (E) AOA-, or vehicle-treated KP mice after infection with control sgTom or sgNf1.3 at 8, 12, 16, and 20 weeks post-infection. Vehicle-treated KP mice are the same control group for (E).",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "(H) Depictions and quantitation of total tumor burden (total tumor area/total lung area) in CB-839-, AOA-, or vehicle-treated KP mice after infection with control sgTom or sgNf1.3 at 20 weeks post-infection. Vehicle-treated KP mice are the same control group in both boxplots. For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "Tom: 
Nf1.3: 18015"
  },
  {
    "caption": "Relative responses of subcutaneous KP and KPΔNF1 tumors treated with vehicle, (B) CB-839, starting from day 12 and measured until day 27 (n = 6 tumors per cell line per treatment) Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": ") Relative responses of subcutaneous KP and KPΔNF1 tumors treated with vehicle, C) AOA starting from day 12 and measured until day 27 (n = 6 tumors per cell line per treatment) Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "Relative responses of subcutaneous KP and KPΔNF1 tumors treated with vehicle, CB-839, or AOA (D) the final masses of these tumors. or boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "Relative responses of orthotopic KP and KPΔNF1 tumors treated with vehicle, (E) CB-839 starting from day 12 and measured until day 27 (n = 24 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "Relative responses of orthotopic KP and KPΔNF1 tumors treated with vehicle, (F) AOA starting from day 12 and measured until day 27 (n = 24 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "ncbi_link": "NF1: 18015"
  },
  {
    "caption": "Relative responses of subcutaneous KP-ix tumors harboring doxycycline (DOX)-inducible gain-of-function (GOF)-Fak1 cDNA treated with vehicle, (G) CB-839, with or without DOX/PIP2 (n = 36 mice per treatment group). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "Fak1: 14083"
  },
  {
    "caption": "Relative responses of subcutaneous KP-ix tumors harboring doxycycline (DOX)-inducible gain-of-function (GOF)-Fak1 cDNA treated with vehicle (H) AOA with or without DOX/PIP2 (n = 36 mice per treatment group). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "Fak1: 14083"
  },
  {
    "caption": "Relative responses of subcutaneous patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (I) CB-839 starting from day 12 and measured until day 30 (n = 6 tumors per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "Relative responses of subcutaneous patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle (J) AOA starting from day 12 and measured until day 30 (n = 6 tumors per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle.",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "Relative responses of orthotopic patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (K) CB-839 starting from day 12 and measured until day 27 (n = 12 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "Relative responses of orthotopic patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (L) AOA starting from day 12 and measured until day 27 (n = 12 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector.",
    "ncbi_link": "NF1: 4763"
  },
  {
    "caption": "(a) Hybridization of DNA from 90 HapMap YRI samples to the Affymetrix SNP 6.0 array reveals a correlated pattern of variation in intensity across six copy-number probes spanning the region upstream of IRGM, suggesting the existence of a common copy-number polymorphism. (Darker shades of red represent reduced hybridization intensity.) Quantitative PCR indicated that the copy-number-variable region was an insertion/deletion (Supplementary Fig. 1).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(d) CD association of typed and imputed polymorphisms in the IRGM region in the NIDDK IBDGC genome scan. Blue trace indicates recombination map. The deletion polymorphism and rs13361189 are indicated by red arrows. rs13361189 (which is in perfect linkage disequilibrium with the deletion, r2 = 1.0) was also the most strongly associated SNP in the combined WTCCC genome scan and replication study.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(a) The exonic SNP rs10065172, which is in strong linkage disequilibrium with the 20-kb insertion/deletion polymorphism upstream of IRGM, can be used to distinguish IRGM transcripts that arise from the deletion haplotype from IRGM transcripts that arise from the reference haplotype. This makes it possible to measure the relative expression of the two haplotypes in heterozygotes by measuring the relative abundance of the two rs10065172 alleles in cDNA. (Yellow and green rectangles indicate transcribed sequence; green rectangles indicate protein-coding sequence.) (b-g) Differential expression of IRGM from the two structural haplotypes in heterozygotes. The relative abundance of the C and T alleles of rs10065172 in cDNA (colored circles) and genomic DNA (black squares) from human tissues and cell lines were measured. Gray squares indicate control measurements for genomic DNA from 48 HapMap YRI individuals, identifying the three reference genotype classes CC, CT and TT. Genomic DNA from all other samples was heterozygous for the C and T alleles (black squares); HeLa genomic DNA (b,c) showed a 2:1 allelic ratio (CCT) reflecting HeLa's triploid 5q karyotypic status. In e, cDNA and genomic DNA from lymphoblastoid cell lines from ten different heterozygous individuals were analyzed: the ten different colors represent the ten individuals; technical replicates from the same cell line are connected by line segments. HeLa, SNU182 and the lymphoblastoid cell lines expressed the C allele of rs10065172 more strongly than the T allele (b-e); HCT116 and primary bronchial cells expressed the T allele much more strongly than the C allele (f,g).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(a) siRNA constructs directed at IRGM reduced endogenous IRGM transcripts by six- to eightfold in HeLa cells. Cells were transfected with control (siControl) or IRGM-targeted (siIRGM1, siIRGM2) siRNA duplexes and assayed 48 h later by quantitative RT-PCR. Error bars, s.d.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(b) IRGM knockdown reduces the efficiency of anti-bacterial autophagy. HeLa cells stably expressing LC3-GFP (a marker for autophagic vesicles) were transfected with control or IRGM-directed siRNA oligos, then infected with S. typhimurium after 48 h. The percentage of bacteria encapsulated in LC3-positive vesicles was determined by microscopy. Reductions in IRGM expression resulted in a significant loss of anti-bacterial autophagy compared to control cells.",
    "ncbi_link": "IRGM: 345611
LC3: 440738///81631///84557"
  },
  {
    "caption": "(c) Microscopic examination reveals a decreased number of autophagically encapsulated bacteria in IRGM knockdown cells. Control siRNA-treated (siControl) and IRGM siRNA-treated (siIRGM1, siIRGM2) cells were infected with S. typhimurium SL1344 and imaged by confocal microscopy. Control cells show numerous bacteria (red in merged image) surrounded by LC3-GFP membranes (green in merged image). Such bacteria-containing autophagosomes (indicated by dashed boxes) were almost completely absent in IRGM-deficient cells. The actin cytoskeleton was visualized using phalloidin (blue in merge). Images are flat projections of confocal z-stacks. Scale bars, 10 μm. (",
    "ncbi_link": "IRGM: 345611
LC3: 440738///81631///84557"
  },
  {
    "caption": "(d) HeLa cells stably expressing LC3-GFP were transfected with increasing amounts of an IRGM expression construct and infected 24 h later with S. typhimurium. The percentage of bacteria found within LC3-positive vesicles increased with increasing amounts of exogenous IRGM. Protein expression levels were confirmed by blotting lysates for Flag-IRGM expression, using an antibody to Flag to detect exogenous IRGM and actin as a loading control (lower panel). Error bars in b and d, s.e.m.",
    "ncbi_link": "IRGM: 345611
LC3: 440738///81631///84557"
  },
  {
    "caption": "HeLa cells stably expressing CHMP4B-eGFP were transfected with siRNAs against: (A) HR 48 h post-transfection cells were used for live-cell imaging experiments. LLOMe was added using perfusion system. A. Depletion of HRS does not alter the dynamics of CHMP4B-eGFP recruitment as compared to siCtrl during treatment with LLOMe Data information: The quantification graphs represent average CHMP4B foci per cell quantified from three independent live-cell imaging experiments per condition. Error bars correspond to 95% confidence intervals. Data from >56 cells per condition were analyzed in each experiment. Right panels show knockdown efficiency of siRNA oligos as detected by Western blot (*, nonspecific immunoreactivity)",
    "ncbi_link": "HR: 6430
HRS: 6430"
  },
  {
    "caption": "HeLa cells stably expressing CHMP4B-eGFP were transfected with siRNAs agains (B) TSG10 48 h post-transfection cells were used for live-cell imaging experiments. LLOMe was added using perfusion system B. Downregulation of TSG101, with two independent siRNAs causes a delay in CHMP4B-eGFP recruitment as compared to siCtrl, indicating an important role of the ESCRT-I complex in recruiting the downstream components Data information: The quantification graphs represent average CHMP4B foci per cell quantified from three independent live-cell imaging experiments per condition. Error bars correspond to 95% confidence intervals. Data from >56 cells per condition were analyzed in each experiment. Right panels show knockdown efficiency of siRNA oligos as detected by Western blot (*, nonspecific immunoreactivity)",
    "ncbi_link": "TSG10: 7251
TSG101: 7251"
  },
  {
    "caption": "HeLa cells stably expressing CHMP4B-eGFP were transfected with siRNAs agains (C) CHMP2 48 h post-transfection cells were used for live-cell imaging experiments. LLOMe was added using perfusion system C. CHMP2A depletion accumulates and stabilizes CHMP4B-eGFP positive foci Data information: The quantification graphs represent average CHMP4B foci per cell quantified from three independent live-cell imaging experiments per condition. Error bars correspond to 95% confidence intervals. Data from >56 cells per condition were analyzed in each experiment. Right panels show knockdown efficiency of siRNA oligos as detected by Western blot (*, nonspecific immunoreactivity)",
    "ncbi_link": "CHMP2: 27243
CHMP2A: 27243"
  },
  {
    "caption": "HeLa cells stably expressing CHMP4B-eGFP were transfected with siRNAs against (D) ALI 48 h post-transfection cells were used for live-cell imaging experiments. LLOMe was added using perfusion system D. siRNA mediated depletion of ALIX shows no significant change on dynamics of CHMP4B recruitment Data information: The quantification graphs represent average CHMP4B foci per cell quantified from three independent live-cell imaging experiments per condition. Error bars correspond to 95% confidence intervals. Data from >56 cells per condition were analyzed in each experiment. Right panels show knockdown efficiency of siRNA oligos as detected by Western blot (*, nonspecific immunoreactivity)",
    "ncbi_link": "ALI: 10015
ALIX: 10015"
  },
  {
    "caption": "HeLa cells stably expressing CHMP4B-eGFP were transfected with siRNAs against (E) both TSG101 and ALIX 48 h post-transfection cells were used for live-cell imaging experiments. LLOMe was added using perfusion system E. Simultaneous depletion of TSG101 and ALIX caused almost no recruitment of CHMP4B upon induction of endolysosomal damage Data information: The quantification graphs represent average CHMP4B foci per cell quantified from three independent live-cell imaging experiments per condition. Error bars correspond to 95% confidence intervals. Data from >56 cells per condition were analyzed in each experiment. Right panels show knockdown efficiency of siRNA oligos as detected by Western blot (*, nonspecific immunoreactivity)",
    "ncbi_link": "ALIX: 10015
TSG101: 7251"
  },
  {
    "caption": "C. Quantification graph showing dynamics of Lysotracker recovery in control (siCtrl) and both TSG101 and ALIX depleted cells. HeLa cells stably expressing CHMP4B-eGFP were co-transfected with siRNAs against TSG101 and ALIX. 48 h post-transfection, cells were pre-treated for 20 min with 75 nM Lysotracker Deep-Red, which was used as a read-out. While the decrease in the number of Lysotracker spots is quickly recovered in siCtrl, simultaneous depletion of ALIX and TSG101 leads to a severe impairment in lysosomal repair. Data from >40 cells per condition from four independent live-cell imaging experiments are shown. Graph is normalized to the area occupied by the cells. Error bars correspond to 95% confidence intervals.",
    "ncbi_link": "ALIX: 10015
TSG101: 7251"
  },
  {
    "caption": "A. HeLa cells were transfected with different siRNAs as indicated. 48 h post-transfection cells were treated with 250 μM LLOMe for 3, 6, 10 hours harvested and stained for Annexin V. Cells were immediately processed for flow cytometry. Already after 3 h of treatment with LLOMe, cells co-transfected with TSG101+ALIX siRNA showed an increase in apoptotic cell death, whereas TSG101 siRNA transfected cells showed elevated Annexin V staining after 6 h of treatment Data information: Graphs show average data from a set of three independent experiments where >10,000 cells per condition were analyzed. Error bars represent SEM. Statistical significance was determined using one-way ANOVA test. p-values are presented where significant. *p-value≤ 0.05, **p-value≤ 0.01 and ***p-value≤ 0.001",
    "ncbi_link": "ALIX: 10015
TSG101: 7251"
  },
  {
    "caption": "A. HeLa cells stably expressing CHMP4B-eGFP were transfected with the mCherry-Galectin3 plasmid. 24 h later, cells were infected with WT Coxiella burnetti. Live-cell imaging started 24 h post-infection and several time points are indicated during the next 24 h of observatio Arrows indicate Coxiella-containing vacuole (DRAQ5 labeling) becoming positive for CHMP4B-eGFP and mCherry-Galectin3. Data information: Scale bars: 50 μm",
    "ncbi_link": "Galectin3: 3958"
  },
  {
    "caption": "B. Bacterial viability and replication assay upon TSG101 KD. HeLa cells were treated with either siCtrl or with two different siTSG101 for 48 h. Then cells were infected with mCherry-Coxiella burnetii for 48 h before lysis and serial dilutions were made to infect Vero cells. 72 h later, infected cells were fixed, DAPI stained and processed for quantitative image analysis. Between 30 and 40 fields representing more than 9,000 cells per condition of three independent experiments were analyzed. Error bars represent SD. Statistical significance was determined using one-way ANOVA test. **p-value≤ 0.01 and ***p-value≤ 0.001.  ",
    "ncbi_link": "TSG101: 7251"
  },
  {
    "caption": "factor.a, Duplicate screens depicting HCoV-229E infection (24 hours post-infection) in Huh7 cells ectopically expressing ISGs.",
    "ncbi_link": "ISGs: "
  },
  {
    "caption": "b, HCoV-229E infection of Huh7 cells expressing LY6E or control vector (Empty). Blue: DAPI, green: HCoV-229E N protein, red: TagRFP encoded in SCRPSY vector.",
    "ncbi_link": "SCRPSY: 
LY6E: 4061"
  },
  {
    "caption": "c-h, Effect of LY6E expression on diverse coronaviruses. Stably transduced cells were infected with HCoV-229E (c), HCoV-OC43 (d), MERS-CoV (e), SARS-CoV (f), SARS-CoV-2 (g), MHV-Gluc (h). Viral replication readouts included: titer determination by plaque assay (c), infectivity by nucleoprotein staining and quantitation by flow cytometry (d), limiting dilution assay (e,f,g), luciferase activity shown as relative light units (RLU) (h,j,l).",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "i, Western blot of WT A549 or two LY6E KO clones (#3, #4).",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "j, HCoV-229E infection of WT or LY6E KO A549.",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "k, Western blot of WT or LY6E KO A549 reconstituted with CRISPR-resistant LY6E (CR LY6E) or control vector (Empty).",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "l, HCoV-229E infection of CR LY6E-reconstituted WT or LY6E KO A549.",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "formation.a-d, VSV pseudoparticles (PP) harboring spike proteins from HCoV-229E (a), MERS-CoV (b), SARS-CoV (c), SARS-CoV-2 (d) were inoculated on LY6E- or empty vector-expressing cells. Virus entry efficiency was quantified by measuring virus-encoded luciferase reporter activity.",
    "ncbi_link": "LY6E: 4061"
  },
  {
    "caption": "e, VSV pseudoparticles expressing VSV G protein on their surface and encoding CoV S protein and GFP (VSV*ΔG(CoV S)) were inoculated with LY6E- or empty vector-expressing Huh7. Syncytia formation was analyzed by immunofluorescence microscopy. Blue: DAPI, green: GFP, red: TagRFP inserted in SCRPSY vector.",
    "ncbi_link": "SCRPSY: 
LY6E: 4061"
  },
  {
    "caption": "h, Cell-cell fusion was measured by co-incubating cells transfected with plasmids encoding CoV S proteins and a split-luciferase construct (DSP1-7) together with CoV permissive LY6E-expressing or control cells transfected with the second fragment of split-luciferase (DSP8-11).",
    "ncbi_link": "luciferase: 
LY6E: 4061"
  },
  {
    "caption": "virus.a-b, Female Ly6efl/fl and Ly6eΔHSC mice were injected with PBS or MHV and monitored for survival (a) and weight loss (b).",
    "ncbi_link": "Ly6e: 17069"
  },
  {
    "caption": "mice.a-e, Transcriptomic analysis from Ly6efl/fl (WT) and Ly6eΔHSC (KO) mice. a-b, Heat maps displaying significant changes (mean RPKM > 0.5; fold change > 2; FDR ≤ 0.05) in liver (a) and spleen (b). Dendrograms are normalized read data (row z-score) clustered with complete linkage method employing Spearman Rank correlation distance measurement.",
    "ncbi_link": "Ly6e: 17069"
  },
  {
    "caption": "(f) Quantification of membrane binding by the indicated mCherry-Atg19 proteins. The experimental set-up is shown in e. The graph is based on three experiments. Shown are the averages and s.d. of these three experiments (N = 3, on the basis of 318 GUVs for Atg19, 171 GUVs for Atg19 W412A, 166 GUVs for Atg19 F376A, F379A, W412A, 188 GUVs for the enhanced GFP (eGFP) control). Scale bars, 5 μm. Abbreviations: 3, Atg3; 5, Atg5; 7, Atg7; 8, Atg8; 12, Atg12; 16, Atg16; 19, Atg19 redundant. Experiments shown in a,b have been conducted twice and the experiment in d three times.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "(d) Quantification of the percentage of GUV-associated eGFP-Ape1-coated beads showing detectable membrane bending. The quantification is based on three independent experiments for the mutant Atg19 versions and 16 independent experiments for wild-type Atg19 and the no-Atg19 control (Atg19, N = 16, total GUVs = 382; Atg19 W412A, N = 3, total GUVs = 55; Atg19 F376A, F379A, N = 3, total 66 GUVs; Atg19 F376A, F379A, W412A, N = 3, total GUVs = 84; Atg19 F376A, F379A, P385A, E386A, W412A, N = 3, total GUVs = 60; Atg19-34, N = 4, total GUVs = 110; no Atg19, N = 16, total GUVs = 382). Shown are the averages and s.d. The experimental set-up is as shown in b; the p-values in c and d were calculated using a two-tailed Student t-test.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "(a) Anti-Ape1 western blot of atg19Δ cells transformed with the indicated expression constructs. The lower Ape1 band indicates prApe1 processing and thus its delivery into the vacuole. Rap., rapamycin; Log.,",
    "ncbi_link": "atg19: 854072"
  },
  {
    "caption": "(b) Representative electron micrographs of ypt7Δ, atg19Δ yeast cells grown under cytoplasm-to-vacuole targetting (Cvt) conditions expressing the indicated proteins labelled with an anti-Myc antibody. The white arrowheads indicate the isolation membrane. The dashed line indicates the circumference of the prApe1 oligomer. Gold particles, 10 nm. Scale bars, 200 nm. See Supplementary Fig. 5 for full images.",
    "ncbi_link": "atg19: 854072
ypt7: 855012"
  },
  {
    "caption": "(c) Quantification of electron micrographs of yeast cells expressing either Myc-Atg19 or Myc-Atg19-Atg34 co-labelled with anti-Myc (10 nm gold) and anti-prApe1 (5 nm gold). See also Supplementary Fig. 5. Three independent experiments; Myc-Atg19, N = 48, Myc-Atg19-34, N = 24.",
    "ncbi_link": "Atg34: 854071"
  },
  {
    "caption": "(d) Anti-Ape1 western blot of atg19Δ cells transformed with the indicated expression constructs. The lower Ape1 band indicates prApe1 processing and thus its delivery into the vacuole. Supplementary Fig. 6 shows the expression of the Myc-tagged proteins and a quantification of the assay.",
    "ncbi_link": "atg19: 854072"
  },
  {
    "caption": "(e) Y2H assay testing for the interaction of Atg11 with Atg19 and the indicated Atg19 mutants.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "(f) Atg19Δ yeast cells expressing the indicated Atg19 proteins and prApe1-RFP (red fluorescent protein) were labelled with the vacuolar membrane dye MDY-64. Scale bars: 2 μM. The experiments in a-d,f have been conducted three times, the experiment in e twice. Images of uncropped western blots and gels can be found in Supplementary Fig. 7.",
    "ncbi_link": "Atg19: 854072"
  },
  {
    "caption": "(D, E) Scatter plot visualization of YFP vs mCherry fluorescence signals in the GCG1 and ORC2 promoter FPR screens. Each data point represents the median signal of a deletion mutant normalized to individual plate median. Highlighted data points represent the mutants of Hda1C (purple), SAGA acetylation module (blue), SAGA deubiquitination module (orange), and cac2∆ (yellow). The regression line is marked in black. The mutants favoring DNC transcription are found above the regression line. The mutants favoring coding transcription are below the regression line. Technical repeat = 1, biological observations = 50,000 individual cells before filtering.",
    "ncbi_link": "cac2: 854869
GCG1: 856910
Hda1C: 855710
ORC2: 852352"
  },
  {
    "caption": "(C) Flow cytometry quantification of mCherry/YFP fluorescence in the mutants with GCG1pr FPR background. The data are normalized to the signal values of the wild type (FPR) strain.",
    "ncbi_link": "mCherry: 
YFP: 
GCG1: 856910"
  },
  {
    "caption": "(D) Endogenous transcript analysis by RT-qPCR in the mutants. The bars represent fold gene expression ratio of coding and divergent transcript normalized to the expression of the reference gene, UBC6.",
    "ncbi_link": "UBC6: 856837"
  },
  {
    "caption": ". (B) NET-seq data at the YPL172C locus. The signal represents NET-seq reads showing nascent transcription at the genomic position of the divergent non-coding strand (black) and the coding strand (grey). The bar graph depicts NET-seq reads as FPKM values for the coding and DNC transcript in the strains ",
    "ncbi_link": "YPL172C: 855931"
  },
  {
    "caption": ". (C) NET-seq data at the YDR261C locus with a novel DNC transcript. Annotations as in (B) ",
    "ncbi_link": "YDR261C: 851848"
  },
  {
    "caption": "(C) A representative image of transcription initiation observed as fluorescence spots in the recorded live-cell movie of wild type strain. The movie output using Python were analyzed and the snapshot was obtained using Image J software. The red and green channel denotes GCG1 and SUT098 transcript initiation, respectively. Images represent maximum intensity projections, and the right and bottom sidebars indicate sideviews in the yz and xz directions, respectively. Scale: 5 µm.",
    "ncbi_link": "GCG1: 856910"
  },
  {
    "caption": "(D, E) Quantification of transcription dynamics by the duration and frequency (time between initiation) of transcription. Bar graphs show the transcription parameters of SUT098 in candidate mutants compared to the wild type strain. The error bars represent SEM calculated by live-cell image analysis of 179, 135, 60 and 129 single-cell biological repeats for WT, hda1∆, hda3∆ and cac2∆ strains, respectively. Statistical significance was calculated by random sampling with replacement method using a bootstrapping algorithm in Python (the asterisk * denotes p-value <0.05).",
    "ncbi_link": "cac2: 854869
hda1: 855710
hda3: 856309"
  },
  {
    "caption": "(A) Flow cytometry data analysis. Bars represent the mCherry/YFP fluorescence ratio of the respective yeast mutants normalized to the signal values of the H3 wild type FPR strain. The error bars show SEM calculated from biological triplicates with three technical repeats. Unpaired two-tailed student's t-test analysis indicates the statistical significance of the mutant compared to the respective wild type. The asterisks *, ** and *** indicate p-values <0.05, <0.01 and <0.001, respectively.",
    "ncbi_link": "mCherry: 
YFP: 
H3: 852295"
  },
  {
    "caption": "Time-lapse images (B) showing colocalization and comigration (white arrows) of Rheb with mitochondria in a retrograde direction along axons during a 148-s recording period. Cortical neurons were transfected with GFP-Rheb and DsRed-Mito at 5-7 DIV and incubated with DMSO or 10 μM CCCP for 24 hr prior to imaging at 10-12 DIV.",
    "ncbi_link": "DsRed: 
GFP: 
Rheb: 6009"
  },
  {
    "caption": "Quantitative analysis showing robust association of Rheb with depolarized mitochondria within axons treated with CCCP. The percentages of mitochondria targeted by Rheb or Rheb-SSVM in the presence or absence of CCCP were quantified, respectively",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "representative images showing robust association of Rheb with depolarized mitochondria within axons treated with CCCP. Rheb-SSVM, a farnesylation deficient mutant of Rheb, fails to be recruited to mitochondria upon dissipating ∆ψm. Mitochondria associated with Rheb were marked by white arrows.",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "F-H Representative dual-channel kymographs (F) and quantitative analysis (G, H) showing that Rheb-mediated mitophagy activation depends on Rheb recruitment to mitochondria through Rheb farnesylation. Note that Rheb, but not Rheb-SSVM, is associated with autophagic vacuoles (AVs) within axons upon ∆ψm dissipation. Rheb-associated AVs move in a predominant retrograde direction along axons. The number of Rheb-associated AVs (Rheb-AVs) with or without CCCP treatment and the relative motilities of AVs and Rheb-AVs in CCCP-treated axons were quantified, respectively",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "Representative dual-channel kymographs showing that Rheb enhances mitophagy in CCCP-treated axons.",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "quantitative analysis showing that Rheb enhances mitophagy in CCCP-treated axons. The numbers of mitochondria (Mito), AVs, and Mito-AVs/mitophagosomes, the percentage of Mito within AVs, were quantified",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "quantitative analysis the percentage of Mito within AVs, and the motilities of AVs and Mito-AVs along axons with and without elevated Rheb expression were quantified",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "D,E Representative images (D) and quantitative analysis (E) showing that mitophagy in axons requires Rheb and Nix, but not Parkin. The number of mitophagosomes indicated by white arrows and the percentage of Mito within AVs in CCCP-treated axons expressing scrambled shRNA, Rheb shRNA, Nix shRNA, or Parkin shRNA were quantified, respectively (E).",
    "ncbi_link": "Nix: 12177
Parkin: 50873
Rheb: 19744"
  },
  {
    "caption": "Quantitative analysis showing that Rheb RNAi augments axonal retention of oxidized mitochondria upon ∆ψm depolarization. The fluorescence of MitoROGFP was emitted at 510 nm and excited at 405 nm or 488 nm, respectively. Mean fluorescence intensity ratios evoked by the two excitation wavelengths at individual mitochondria in the CCCP-treated axons expressing scrambled shRNA or Rheb shRNA were quantified and normalized to those of control neurons transfected with scrambled shRNA (H).",
    "ncbi_link": "Rheb: 19744"
  },
  {
    "caption": "representative images showing that Rheb RNAi augments axonal retention of oxidized mitochondria upon ∆ψm depolarization. The fluorescence of MitoROGFP was emitted at 510 nm and excited at 405 nm or 488 nm, respectively. Ratiometric images were generated from fluorescence excited by 405 nm light relative to that excited by 488 nm light. The ratio has been false colored with the indicated heat map, with high intensity indicative of ROGFP fluorescence in a more oxidative level",
    "ncbi_link": "Rheb: 19744"
  },
  {
    "caption": "Aberrant accumulation of mitophagosomes co-labeled by antibodies against LC3 and cytochrome c (Cyto c) in the hippocampal mossy fibers of mutant hAPP Tg mouse brains. Note that mitophagosomes indicated by white arrows are not readily observed in WT mouse brains",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "Quantitative analysis showing presynaptic retention of mitophagosome-like structures in the hippocampal regions of mutant hAPP mouse brains. Data were quantified from the total number of the imaging fields (n) indicated in parentheses",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "representative TEM images showing presynaptic retention of mitophagosome-like structures in the hippocampal regions of mutant hAPP mouse brains. White arrow-labeled mitophagosomes are not readily detected in WT mouse brains. Black arrows marked amphisomes or degradative autophagic vacuoles (AVd).",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "F,G Mitophagic accumulation at Aβ-enriched synapses in AD mouse brains. Note that the levels of mitophagic/autophagic proteins (red box) along with Aβ (green box) are increased in synaptic fractions isolated from AD mouse brains. Equal amounts (10 μg) of synaptosomal preparations (Syn) and post-nuclear supernatants (PNS) from WT and mutant hAPP mouse brains were sequentially immunoblotted with antibodies against hAPP/Aβ, Rheb, LC3, p62, and Rab7, as well as mitochondrial proteins TOM20 and SOD2 on the same membrane after stripping between each antibody application. The purity of synaptosomal fractions was confirmed by relative enrichment of SYP and less abundance of p115 and GAPDH (F). Relative protein levels in the synaptosomal preparations from mutant hAPP mice were compared to those in WT littermate controls. Data were quantified from five repeats (G).",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "Representative images showing increased mitochondrial association with Rheb in AD axons, relative to that of WT littermate controls. Note that CCCP treatment enhances Rheb localization to mitochondria. The percentages of white arrow-marked mitochondria that were targeted by Rheb in WT and mutant hAPP axons in the absence and presence of CCCP",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "quantitative analysis The percentages of white arrow-marked mitochondria that were targeted by Rheb in WT and mutant hAPP axons in the absence and presence of CCCP were quantified, respectively",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "C- Representative dual-channel kymographs showing defective retrograde transport and mitophagic accumulation within AD axons. mitochondria within AVs in WT or mutant hAPP axons with and without CCCP were quantified",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "quantitative analysis , the numbers of Mito, AVs, and Mito-AVs, and the percentage of mitochondria within AVs in WT or mutant hAPP axons with and without CCCP were quantified, respectively",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "quantitative analysis Relative motility of AVs and Mito-AVs/mitophagosomes in WT or mutant hAPP axons with and without CCCP were quantified",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "F,G Quantitative analysis (F) and representative blots (G) showing that ∆ψm depolarization augments mitophagy activation in cortical neurons cultured from AD mouse brains. Note increased localization of Rheb along with LC3-II and Rab7 to mitochondria in mutant hAPP Tg neurons after CCCP treatment (red box). Data were quantified from three independent repeats. P: post-nuclear supernatants; M: mitochondria-enriched membrane fractions; S: cytosolic supernatants.",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "Quantitative analysis Mean fluorescence intensity ratios evoked by the two excitation wavelengths (405 nm and 488 nm) at individual mitochondria in mutant hAPP axons with and without CCCP treatment were quantified and normalized to those of WT controls",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "representative images showing abnormal accumulation of oxidatively damaged mitochondria in AD axons, which is exacerbated after dissipating ∆ψm. Mean fluorescence intensity ratios evoked by the two excitation wavelengths (405 nm and 488 nm) at individual mitochondria in mutant hAPP axons with and without CCCP treatment were quantified and normalized to those of WT controls",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "A,B Representative images (A) and quantitative analysis (B) showing aberrant accumulation of mitophagosomes labeled by LC3 and Cyto c antibodies in the hippocampal mossy fibers of snapin-cKO mouse brains. Note that white arrow-labeled mitophagosomes are not readily observed in WT mouse brains. The average number of mitophagosomes per section (320 μm × 320 μm) was quantified.",
    "ncbi_link": "snapin: 20615"
  },
  {
    "caption": "Representative blots showing aberrant mitophagic retention at synaptic terminals in snapin-mutant mouse brains. The levels of Rheb along with LC3-II, p62, and Rab7 are significantly elevated in the synaptosomal fractions (Syn) purified from snapin-deficient mouse brains, relative to those of WT littermate controls (red box). Equal amounts (10 μg) of Syn and post-nuclear supernatants (PNS ) from WT and snapin-mutant mouse brains were sequentially immunoblotted with antibodies against Snapin, mitophagic/autophagic proteins, and mitochondrial proteins VDAC and TOM20 on the same membrane after stripping between each antibody application. The purity of synaptosomal fractions was confirmed by relative enrichment of SYP and PSD95 and less abundance of GAPDH.",
    "ncbi_link": "snapin: 20615"
  },
  {
    "caption": "quantitative analysis The levels of Rheb along with LC3-II, p62, and Rab7 are significantly elevated in the synaptosomal fractions (Syn) purified from snapin-deficient mouse brains, relative to those of WT littermate controls WT and snapin-mutant mouse brains were sequentially immunoblotted with antibodies against TOM20 on the same membrane after stripping between each antibody application. The purity of synaptosomal fractions was confirmed by relative enrichment of SYP and PSD95 and less abundance of GAPDH. Data were quantified from five independent repeats.",
    "ncbi_link": "snapin: 20615"
  },
  {
    "caption": "E,F Representative blots (E) and quantitative analysis (F) showing mitophagic accumulation in the brains of snapin conditional KO (cKO) mice by crossing with Thy1-cre Tg mice. Note increased levels of Rheb along with LC3-II, p62, and Rab7 in mitochondrial (Mito) fractions isolated from snapin-deficient mouse brains, relative to those of WT littermate controls (red box). Data were quantified from five independent repeats. PNS: post-nuclear supernatants.",
    "ncbi_link": "cre: 2777477
snapin: 20615
Thy1: 21838"
  },
  {
    "caption": "G,H Representative TEM images (G) and quantitative analysis (H) showing abnormal presynaptic retention of mitophagosome-like structures in the hippocampal regions of snapin-deficient mouse brains. Mitophagosomes, indicated by black arrows, are not readily detected in WT mouse brains. Data were quantified from the total number of the imaging fields (n) indicated in parentheses (H).",
    "ncbi_link": "snapin: 20615"
  },
  {
    "caption": "I,J Representative images (I) and quantitative analysis (J) showing that deletion of snapin in mouse brains induces synaptic damage. Note that the density of presynaptic terminals in the hippocampal mossy fibers revealed by SYP immunostaining is significantly reduced in snapin-mutant mice crossed with CamKII-cre Tg mice at the age of 8 months, relative to that of WT littermate controls.",
    "ncbi_link": "CamKII: 12322
cre: 2777477
snapin: 20615"
  },
  {
    "caption": "Representative dual-channel kymographs (A) and quantitative analysis (B showing that overexpression of Snapin, but not Snapin-L99K, a Snapin mutant deficient in dynein motor binding, reduces mitophagic accumulation within AD axons incubated with CCCP.",
    "ncbi_link": "Snapin: 20615"
  },
  {
    "caption": "Representative quantitative analysis showing that overexpression of Snapin, but not Snapin-L99K, a Snapin mutant deficient in dynein motor binding, enhances retrograde transport of mitophagosomes within AD axons incubated with CCCP.",
    "ncbi_link": "Snapin: 20615"
  },
  {
    "caption": "D Mean fluorescence intensity ratios evoked by 405 nm and 488 nm excitation wavelengths at individual mitochondria in mutant hAPP axons expressing Snapin or Snapin-L99K were quantified and normalized to those of mutant hAPP controls. Note that oxidatively stressed mitochondria are reduced within AD axons expressing Snapin after CCCP treatment.",
    "ncbi_link": "hAPP: 351
Snapin: 20615"
  },
  {
    "caption": "A Representative images showing gene delivery into the hippocampus of AD mice injected with AAV-mCherry or AAV-mCherry-Snapin. mCherry fluorescence indicated by white arrows is present in the soma and processes of transduced neurons in the hippocampal CA3 and dentate gyrus (DG) of mutant hAPP mouse brains. NeuN, a neuronal nuclear marker, indicates neurons.",
    "ncbi_link": "mCherry: 
hAPP: 351
Snapin: 20615"
  },
  {
    "caption": "Attenuation of mitophagic accumulation in the hippocampal mossy fibers of AD mice transduced with AAV-mCherry-Snapin. Note a marked reduction of mitophagosomes (white arrows) in mutant hAPP Tg mouse brains with elevated Snapin expression Cyto c*: color is converted from blue to red for better contrast",
    "ncbi_link": "mCherry: 
hAPP: 351
Snapin: 20615"
  },
  {
    "caption": "Attenuation of mitophagic accumulation in the hippocampal mossy fibers of AD mice transduced with AAV-mCherry-Snapin. Note a marked reduction of mitophagosomes (white arrows) in mutant hAPP Tg mouse brains with elevated Snapin expression",
    "ncbi_link": "mCherry: 
hAPP: 351
Snapin: 20615"
  },
  {
    "caption": "D,E Quantitative analysis (D) and representative images (E) showing increased density of presynaptic terminals in the hippocampal mossy fibers of AD mice infected with AAV-mCherry-Snapin. Blue indicates the signal of DAPI staining. The percentage area of SYP-labeled presynaptic terminals was quantified and normalized to that of control AD mice injected with AAV-mCherry (D). Data information: Data were quantified from a total number of 40-44 imaging slice sections of three pairs of mutant hAPP Tg mice with AAV injection.",
    "ncbi_link": "mCherry: 
hAPP: 351
Snapin: 20615"
  },
  {
    "caption": "mRNA expression by qRT-PCR of Rab5, Rab7a, Rab7b, and Rab9. Significance determined by one-way ANOVA, Tukey post hoc. Each data point represents the mean of triplicate technical replicates from a single mouse, n=3-4 mice in independent experiments. Error bars denote standard deviation.",
    "ncbi_link": "Rab5: 271457
Rab7a: 19349
Rab7b: 226421
Rab9: 56382"
  },
  {
    "caption": "ChIP-PCR on mouse stomach tissue at vehicle and 6 hour HDT. Chromatin probed with ATF3, Histone H3 antibodies, or a Rabbit IgG control. Also included is the 2% chromatin input and water to control for DNA contamination. Rab7b amplicon is from a conserved, putative ATF3-binding site in the first intron. Amplicon from Atf3 is a positive control from a previously characterized ATF3-binding site; negative control is from a site in Rab9a lacking putative ATF3 binding motifs.",
    "ncbi_link": "Atf3: 11910
Rab7b: 226421
Rab9a: 56382"
  },
  {
    "caption": "mRNA expression of ATF3 by qRT-PCR in control, ATF3 knockdown (KD), and ATF3 overexpression (OE) AGS cell lines generated using a PiggybacTM transposon system. Significance by one-way ANOVA, Dunnett post-hoc. Datapoint = mean of technical triplicates in a single mouse. n=3 mice. Error bars denote standard deviation. mRNA expression of RAB7B by qRT-PCR in AGS cell lines from 3A. Statistics and plotting as for panel A.",
    "ncbi_link": "ATF3: 11910
RAB7B: 226421"
  },
  {
    "caption": "Top - Immunofluorescence for RAB7 (red) and DAPI (blue, nuclei) in control, ATF3 knockdown (KD), and ATF3 overexpression (OE) AGS cells. Arrowhead indicates aggregated RAB7 vesicular formation similar to those observed in tissue. Bottom - Immunofluorescence for ATF3 (purple) and Cathepsin D (CTSD, green, lysosomes) in AGS cells. Scale bar, 20µm.",
    "ncbi_link": "ATF3: 11910"
  },
  {
    "caption": "Representative immunofluorescence images of gastric chief cells after vehicle or 24h HDT treatment stained for Pepsinogen C (PGC, red, granules) and MAP1LC3B (green, autophagy marker). Top row is wild-type, bottom row is Atf3−/−. Scale bar, 50μm. Stomach unit base outlined by dashed white line.",
    "ncbi_link": "Atf3: 11910"
  },
  {
    "caption": "Transmission electron micrograph images of zymogenic chief cells (ZCs) after 24h vehicle or HDT treatment in WT (top) and Atf3−/− mice (bottom). Scale bar, 1μm. Arrowheads indicate cell components being degraded. Quantification of degradation events per cell counted from EM images of ZCs after 24h HDT treatment in WT and Atf3−/−mice as shown in panel 3D. Each data point=total granules in a cell in a single TEM section with cells from 2 separate mice plotted together (data point colors indicate cells from a single mouse). Red line indicates mean across all the mice.",
    "ncbi_link": "Atf3: 11910"
  },
  {
    "caption": "Representative immunofluorescence images of gastric units after vehicle or 72h high-dose tamoxifen (HDT) treatment stained for GIF (red, granules), GSII (green, neck cells and SPEM marker), BRDU (white, proliferation) and DAPI (blue, nuclei). Top row is wild-type, bottom row is Atf3−/−. Yellow arrowheads point to areas of base dropout where ZCs have been lost. Scale bar, 50μm. Stomach units outlined by dashed white line.",
    "ncbi_link": "Atf3: 11910"
  },
  {
    "caption": "Representative immunohistochemistry of Cleaved-Caspase 3 in pancreatic acinar cells marking apoptosis in vehicle or 24h cerulein (CER) treatment. Top row is WT, bottom row is Atf3−/−. Scale bar, 50μm. Apoptosis quantified following 24h CER injury by the number of Cleaved-Caspase 3+ cells from a 40x field. Each data point is mean of positive cells in 4-5 40x fields in an individual mouse, n=3 mice per treatment group. Significance by unpaired two-tailed t-test. Error bars denote standard deviation.",
    "ncbi_link": "Atf3: 11910"
  },
  {
    "caption": "Representative immunohistochemistry of BrdU in pancreatic acinar cells marking proliferation in vehicle or 7 days of repeated cerulein injury. Top row is WT, bottom row is Atf3−/−. Scale bar, 50μm. Quantification of proliferation at peak ADM as counted by the number of BrdU+ cells from a 20x field following 7D cerulein treatment. Plotting and statistical analysis as per panel F.",
    "ncbi_link": "Atf3: 11910"
  },
  {
    "caption": "(A) mRNA expressions  of PINK1  in CSCs  and non-CSCs. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(Q) CSCs  transfected with PINK1  shRNA or the control were analysed for  sphere formation  and tumorgenicity. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(S) CSCs   were transfected with PINK1  shRNA or control, and analysed for activated Notch1. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(T) CSCs  with or without transfection of Notch1  ICD were treated with Mdivi-1 (50 μM) and analyzed for sphere formation plus tumorgenicity. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Notch1: 4851"
  },
  {
    "caption": "(E) CSCs  with or without transfection of PINK1  shRNA were analysed for lysosomal mtDNA. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(L) CSCs  transfected with DNase II  expression vector or the control were analyzed for lysosomal DNA  plus MyD88  protein. Mean±SEM from 6 patients. (M) CSCs  transfected with  DNase II shRNA or the control were analyzed for lysosomal DNA  plus MyD88  protein. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "DNase II: 1777"
  },
  {
    "caption": "(D) CSCs  were transfected with 2 different TLR9  shRNAs or the control, and analysed for  sphere formation and tumorgenicity. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "TLR9: 54106"
  },
  {
    "caption": "(E-F) CSCs  transfected with  DNase II expression vector, DNase II shRNA, or the control was analyzed for sphere formation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "DNase II: 1777"
  },
  {
    "caption": "(A) CSCs  transfected with TLR9  shRNA or control were analysed for protein expressions  of activated Notch1  plus HES1. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "TLR9: 54106"
  },
  {
    "caption": "(C) CSCs  transfected with  DNase II  expression vector or control were analyzed for activated Notch1 expression. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "DNase II: 1777"
  },
  {
    "caption": "(F) CSCs  were transfected with 2 different Notch1  shRNAs or control, treated with CpG ODN  (10 μg/ml), and analyzed for sphere formation  plus tumorgenicity. Mean±SEM from 6 experiments. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Notch1: 4851"
  },
  {
    "caption": "(D) CSCs  transfected with Notch1  shRNA or control shRNA were analysed for mitochondrial OCR. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Notch1: 4851"
  },
  {
    "caption": "(F) CSCs  transfected with DNase II expression vector or control were analysed for mitochondrial OCR. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method **p < 0.01, ***p < 0.001.",
    "ncbi_link": "DNase II: 1777"
  },
  {
    "caption": "(C) CSCs  transfected with Notch1  shRNA or control were stimulated with  CpG ODN (10 μg/ml) and analyzed for phosphor-AMPKα. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method , **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "Notch1: 4851"
  },
  {
    "caption": "(G) CSCs  were transfected with 2 different AMPKα  shRNA or the control, stimulated with  CpG ODN (10 μg/ml), and analysed for mitochondrial OCR. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method , **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "AMPKα: 5562///5563"
  },
  {
    "caption": "(A) CSCs  transfected with or without Notch1  ICD were analyzed for AMP/ATP  ratio plus LKB1 phosphorylation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Notch1: 4851"
  },
  {
    "caption": "(D) CSCs  transfected with LKB1  shRNA（right）or the control (left) were treated with CpG ODN (10 μg/ml) and analysed for AMPK phosphorylation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "LKB1: 6794"
  },
  {
    "caption": "(E) CSCs  transfected with TAK1  shRNA or the control were treated with CpG ODN  (10 μg/ml) and analysed for AMPK phosphorylation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "TAK1: 7182"
  },
  {
    "caption": "(F) CSCs  transfected with LAMTOR1  shRNA or the control were treated with CpG ODN (10 μg/ml) and analysed for AMPK phosphorylation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "LAMTOR1: 55004"
  },
  {
    "caption": "(G) CSCs  transfected with AXIN1  shRNA or the control were treated with CpG ODN  (10 μg/ml) and analysed for AMPK phosphorylation. Mean±SEM from 6 patients. Data information: Paired t-test with Bonferroni method, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "AXIN1: 8312"
  },
  {
    "caption": "G. RT-qPCR analyses of FACS-purified CD34+α6+ and CD34-α6+ cells from either 3C cultures or from freshly isolated epidermis show upregulation of HFSC identity in both freshly isolated and 3C-CD34+α6+ cells compared to freshly isolated CD34-α6+ progenitors. 3C- CD34-α6+ cells show intermediated expression (mean ±SEM; n=4; *p ≤ 0.05, ** p ≤ 0.01, Kruskal-Wallis).",
    "ncbi_link": "CD34: 12490"
  },
  {
    "caption": "Labelling scheme and representative DNA fibers from U2OS cells transfected with siLuc or siChk1.",
    "ncbi_link": "Luc: 
Chk1: 1111"
  },
  {
    "caption": "Control (siLuc) and Chk1-depleted (siChk1) U20S cells were labeled with CldU and IdU for 10 and 30 min, respectively. Mean (+SEM) track lengths (top) and CldU/IdU ratios (bottom) are shown. Data come from 6 independent experiments and a total of 579 (siLuc) and 590 (siChk1) fibers were scored.",
    "ncbi_link": "Luc: 
Chk1: 1111"
  },
  {
    "caption": "U2OS cells were labeled with CldU for 10 min, followed by increasing IdU labelling times and subjected to DNA stretching. IdU track length after 10-80 min. Theoretical IdU track lengths are shown in red; the theoretical 10-min points were considered equal to the experimental values obtained for siLuc or siChk1, and the following theoretical points were calculated proportionally. Data were calculated as the mean (+SD) of mean IdU track lengths (B) n=4 for IdU times 20-60 min or n=3 for IdU times 10 and 80 min; for each experiment and condition 60-100 fibers were scored.",
    "ncbi_link": "Luc: 
Chk1: 1111"
  },
  {
    "caption": "DNA combing from HCT116 cells labeled with CldU and IdU for 20 min. The upper left panel shows the labelling scheme. The upper right panel shows representative sister replication forks that emanate from the same origin (ORI=origin of replication); a pair of sister forks is considered asymmetric if their lengths (CldU+IdU) differ in more than 33%. The percentage of asymmetric forks (lower left panel; a Western Blot of Chk1 and Ku80, loading control, performed in parallel to the combing experiments, is shown) and the lengths of each pair of forks (lower right panel; points outside of the dotted lines correspond to asymmetric forks) are shown. Data (siLuc, n=131; siChk1, n=117) come from 2 independent experiments; the numbers indicate the mean (+SD) percentage of asymmetric forks.",
    "ncbi_link": "Luc: 
Chk1: 1111"
  },
  {
    "caption": "Representative images of siChk1-depleted U2OS cells showing nuclear localization of GFP-Polη-WT/S687A/S687D. Numbers indicate percentage of cells showing nuclear GFP-Polη (mean+SD, n=2). Scale bar: 100 μm.",
    "ncbi_link": "GFP: 
Polη: 
Chk1: 1111"
  },
  {
    "caption": "Western Blot of GFP-Polη in U2OS cells, 48/24 h after transfection with siRNA/GFP(-Polη). Actin was used as loading control.",
    "ncbi_link": "GFP: 
Polη: "
  },
  {
    "caption": "IdU track lengths from U2OS cells transfected with GFP (-) or GFP-Polη-WT/S687A/S687D. >180 fibers obtained from 2 independent experiments were measured for each condition.",
    "ncbi_link": "GFP: 
Polη: "
  },
  {
    "caption": "Number of foci per cell after CSK extraction in siLuc and siChk1-depleted U2OS cells transfected with GFP-Polη-WT/S687A/S687D. >150 cells/sample were analyzed in 4 independent experiments. p<0.05 was considered significant.",
    "ncbi_link": "GFP: 
Luc: 
Chk1: 1111
Polη: 353497"
  },
  {
    "caption": "IdU track lengths and percentage of origin firing (mean+SD) from U2OS cells transfected or not with siCDT1. Track lengths from >290 fibers obtained from 3 independent experiments were measured for each condition. To calculate origin frequency >700 DNA fibers from 3 independent experiments were scored.",
    "ncbi_link": "CDT1: 81620"
  },
  {
    "caption": "IdU track lengths and percentage of origin firing (mean+SD) from U2OS cells transfected or not with GFP-Polη. >180 (track length) and >400 (origin frequency) DNA fibers obtained from 2 independent experiments were measured for each condition.",
    "ncbi_link": "GFP: 
Polη: "
  },
  {
    "caption": "DSB accumulation measured by neutral comet assay after 8 h treatment with Chk1i, in the presence of 5 μM NS, siCDC7 or 10 μM roscovitine. 85-170 cells/sample were analyzed in 2 independent experiments. Representative images of data shown in (D). Scale bar: 25 μm.",
    "ncbi_link": "CDC7: 8317"
  },
  {
    "caption": "Sensitivity of U2OS cells to Chk1 inhibition, roscovitine (5 μM) and Polη depletion. Cell number was determined 4 days after a 24 h treatment (5 days in total) with Chk1i±Rosc. Data represent the mean (+SD) of 3 independent experiments.",
    "ncbi_link": "Polη: 353497"
  },
  {
    "caption": "Sensitivity of U2OS cells transduced with shRNA targeting Chk1 (shChk1) or non-targeting shRNA (shScr) and Lenti-GFP-Polη or Lenti-GFP (-). Cell number was determined 7 days after transduction (5 days after maximal downregulation). Data represent the mean (+SD) of 3 independent experiments.",
    "ncbi_link": "GFP: 
Polη: 
Chk1: 1111"
  },
  {
    "caption": "IdU track lengths from U2OS cells. >170 DNA fibers obtained from 2 independent experiments were measured for each condition. For comparison, the data showing that Polη is required for roscovitine-dependent rescue of fork elongation in Chk1-depleted cells (Fig 3B) is shown on the right. The lower panel shows the corresponding Western Blot of Chk1, Polη and CDC45. Actin was used as a loading control.",
    "ncbi_link": "Chk1: 1111
Polη: 353497"
  },
  {
    "caption": "Sensitivity of U2OS cells to Chk1 and CDC45 depletion. Cell number was determined 7 days after transfection (5 days after maximal downregulation). Data represent the mean (+SD) of 2 independent experiments. Representative image of data shown in (E). Scale bar: 100 μm.",
    "ncbi_link": "CDC45: 8318
Chk1: 1111"
  },
  {
    "caption": "Distribution of the plasma membrane reporter PH::GFP in control cells (A-A'') and in cells where dynamin activity had been blocked using a temperature-sensitive allele of dynamin (shibirets In (B), was inactivated at the onset of tube formation (C-D) Distribution of PH::GFP fluorescence intensity in control and shibirets cells. Data from 1-2 minute-interval time lapses was collected in windows of 20 minutes each (except for t=0). (C) Proportion of signal in the apical and in the basal membrane compartment over time in control cells (n=4) and also in cells where dynamin was inactivated (n=5), *p=0.015, Mann-Whitney test. (D) Total fluorescence intensity of PH::GFP over time in controls (n=4) and in cells where dynamin was inactivated (n=5), n.s.: p=0.063, Mann-Whitney test.",
    "ncbi_link": "shibire: 45928"
  },
  {
    "caption": " Distribution of the plasma membrane reporter PH::GFP in cells where dynamin activity had been blocked using a temperature-sensitive allele of dynamin (shibirets in (E) it was inactivated ~15 minutes after the tube had begun to form. ",
    "ncbi_link": "shibire: 45928"
  },
  {
    "caption": " (A-F) TEM tomograms and 3D reconstructions of terminal cells in shibirets embryos. (A) Control. (B-F) Kept at 34ºC for 1 (B, E) or for 2 hours (C, D, F). Boxed regions in (A) and (B) are magnified in (A'') and (B''). (A', B') Reconstructed 3D models. The tube membrane (cyan) is characterized by the electron-dense apical extracellular matrix (aECM). Invaginations with connections that can be traced to the tube membrane are red, invaginations from the basal plasma membrane are green. The basal membrane is light pink. (C-D') shibirets terminal cell after 2 hours at 34ºC. (C') 3D reconstruction, color coding for basal and tube membrane is the same as above. Membrane that is continuous with both the apical and the basal membrane is shown in green, purple and dark blue. (D-D') higher magnification of a region in the same cell at a level where membrane sheets (purple, dark blue) bridge the apical and basal plasma membrane domains. (E-E'') Two focal planes and model of a tomogram from the cell shown in (B) where a basal (pink arrowhead) and an apical invagination (blue) are seen in close proximity (closest distance is marked by cyan and blue arrowheads). (F-F') apical membrane overgrowth regions of the cell shown in (C). The genotype of the embryos was shibirets; btl>KDEL::RFP, Par3::YFP. The cell shown in (C-D) was found and acquired without the CLEM approach. ",
    "ncbi_link": "KDEL: 
Par3: 
btl: 39564
shibire: 45928"
  },
  {
    "caption": "(A-B) Terminal cells expressing the membrane marker CD4::mIFP under btl-gal4 and FGFR::GFP under its own promoter (from the fTRG library). (A) Time lapse imaging of a control cell. Blue arrowheads point to filopodia and basal plasma membrane and red ones point to puncta containing CD4::mIFP and FGFR::GFP. (B) shibirets cell imaged before dynamin inactivation, after 23 and 45 minutes of inactivation, and after 30 minutes of recovery. White arrowheads point to FGFR::GFP accumulation at the apical compartment.",
    "ncbi_link": "gal4: 
btl: 39564
shibire: 45928"
  },
  {
    "caption": "High time resolution imaging of the membrane marker CD4::mIFP expressed under btl-gal4. (A) Example of a large CD4 vesicle (arrowhead) rapidly moving towards the tip of the terminal cell. (B-D) Analysis of 28 CD4 vesicles in five terminal cells.",
    "ncbi_link": "gal4: 
btl: 39564"
  },
  {
    "caption": "(A-F) Terminal cells expressing CD4::mIFP and FYVE::GFP under btl-gal4. The outline of the cells was traced using the CD4::mIFP signal and is shown as a blue dashed line. (A-C) Control cell. (D-F) shibirets cell before 34ºC (D), after 30 minutes at 34ºC (E) and after 30 minutes of recovery (F). Red arrowheads: FYVE::GFP puncta.",
    "ncbi_link": "gal4: 
btl: 39564
shibire: 45928"
  },
  {
    "caption": " (G-H) Number of FYVE::GFP vesicles in 4 control cells (G) and in 6 shibirets cells (H). Box plots represent median, interquartile range (IQR), and IQR*1.5 below and above the IQR. Significance in (H) was assessed using one-way ANOVA with Geisser-Greenhouse correction for paired data and Dunnett's multiple comparisons test. *p=0.0288, ***p=0.0016. ",
    "ncbi_link": "shibire: 45928"
  },
  {
    "caption": "(I) shrbO3/G5 mutant cell expressing CD4::mIFP under btl-gal4. Arrowhead: CD4::mIFP aggregation.",
    "ncbi_link": "gal4: 
btl: 39564
shrb: 35933"
  },
  {
    "caption": "(J-K) Terminal cells over-expressing Shrb::GFP under btl-gal4 together with PH::mCherry (J), or together with Spin::RFP and CD4::mIFP (K). Arrowheads: Shrb::GFP accumulations.",
    "ncbi_link": "gal4: 
GFP: 
btl: 39564
Shrb: 35933"
  },
  {
    "caption": "(L-M) Dorsal trunk cells stained for Serp. In control embryos (L), Serp is seen exclusively in the tracheal lumen. The cells themselves are not visible in these images. In embryos expressing Shrb::GFP under btl-gal4 (M), Serp is also seen inside the cells, usually in association with or surrounded by Shrb::GFP. Boxed regions are magnified in (L'-M') and shown as single confocal planes.",
    "ncbi_link": "gal4: 
GFP: 
btl: 39564
Shrb: 35933"
  },
  {
    "caption": "C. Cathepsin activity  assay in WT and Tpl2[D270A] BMDMs 0.5 h after uptake of  latex beads. BMDMs were stained with the Magic Red cathepsin L substrate (red). Average fluorescence intensity of the cathepsin probe per cell was quantified (n = 40-51 cells). E. pH assay in WT and Tpl2[D270A] BMDMs upon 0.5 h after incubation with  latex beads. BMDMs were stained  with the LysoTracker Red DND-99 dye  (red). Average  fluorescence intensity of the  Lysotracker Red probe per cell was quantified (n = 95-126 cells). Data information: One representative experiment out of three shown. Error bars and shaded areas represent SEM. **** P < 0.0001. Student's unpaired t-test.",
    "ncbi_link": "Tpl2: 26410"
  },
  {
    "caption": "G. Reactive oxygen species assay in WT and Tpl2[D270A] BMDMs upon 0.5 h after incubation with latex beads. BMDMs were stained with the ROS Deep Red dye. Average fluorescence intensity of the ROS Deep Red probe per cell was quantified (n = 80-110 cells) Data information: One representative experiment out of three shown. Error bars and shaded areas represent SEM. **** P < 0.0001. Student's unpaired t-test.",
    "ncbi_link": "Tpl2: 26410"
  },
  {
    "caption": "Experiments were performed using murine BMDMs. (C) Cell extracts from LPS-stimulated Nfkb1[SSAA] and Nfkb1[SSAA]/Tpl2[D270A] BMDMs were immunoblotted  for the indicated antigens.",
    "ncbi_link": "Tpl2: 26410
Nfkb1: 18033"
  },
  {
    "caption": "C. Protein intensities of V-ATPase subunits from phagosomes purified from WT and Tpl2[D270A] BMDMs, (n = 3 biological replicates). Data information: Data were analysed by Student's t-test. Error bars represent SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.",
    "ncbi_link": "Tpl2: 26410"
  },
  {
    "caption": "D. Protein intensities of RAB5 and LAMP-1 from phagosome proteome analysis of WT and Tpl2[D270A] BMDMs (n = 3 biological replicates) (left). Immunoblot of isolated phagosomes from WT and Tpl2[D270A] BMDMs probed for RAB5,  LAMP-1  and vimentin. Phagosomal fractions of two biological replicates were pooled. One representative experiment out of two shown (right) (n = 2). Data information: Data were analysed by Student's t-test. Error bars represent SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. ",
    "ncbi_link": "Tpl2: 26410"
  },
  {
    "caption": "A. TPL-2-dependent phosphoproteome following phagocytosis of latex beads  (0.5 h) was determined by TMT mass spectrometry. Volcano plot representing the significance (-log10 P-values after Welch's t-test) vs. phosphorylation  fold change (Welch difference ratios) between WT and Tpl2[D270A] BMDMs. Five biological replicates were analysed per genotype (n = 5). Three of the most highly and significantly downregulated phospho-sites in Tpl2[D270A]  BMDMs relative to WT, as well as unaltered DMXL1 phospho-sites, are shown.",
    "ncbi_link": "Tpl2: 26410"
  },
  {
    "caption": "U-2 OS cells stably expressing GFP-MDC1 or GFP-53BP1 were treated with 1 Gy of IR and analyzed by live cell microscopy at 15 min intervals. Representative images are provided and kinetics of GFP-MDC1 and GFP-53BP1 foci formation and dissolution are shown as single cell tracks. Bold lines represent averages from n=29 for GFP-MDC1 and n=18 for GFP-53BP1 cells.",
    "ncbi_link": "GFP: 
MDC1: 9656
53BP1: 27223"
  },
  {
    "caption": "GFP-53BP1 cells were treated with 25 ng/ml NCS to induce DNA breaks and imaged at 30 minutes intervals. Examples of GFP-53BP1 fusions (green arrowheads and magnified regions) and fissions (blue arrowheads and magnified regions) are shown.",
    "ncbi_link": "GFP: 
53BP1: 27223"
  },
  {
    "caption": "53BP1-RFP cells, in which the endogenous 53BP1 gene locus had been engineered by CRISPR/Cas9 to express 53BP1-mScarlet from the natural promoter, were treated with NCS (25 ng/ml) and imaged at 30 minutes intervals. Examples of 53BP1 fusions (green arrowheads and magnified regions) and fissions (blue arrowheads and magnified regions) are shown on the left and in higher magnification on the right.",
    "ncbi_link": "CRISPR: 
RFP: 
53BP1: 7158"
  },
  {
    "caption": "GFP-53BP1 cells were left untreated, or treated with APH (0.5 μM) or ATRi (1 μM) to induce replication stress-associated heritable DNA lesions, and cells were imaged at 30 minutes intervals. Examples of 53BP1 fusions (green arrowheads and magnified regions) are shown.",
    "ncbi_link": "GFP: 
53BP1: 27223"
  },
  {
    "caption": "Light-induced optoDroplet formation of Cry2-mCherry-53BP1, Cry2-mCherry-53BP1 W1495A, and Cry2-mCherry-MDC1. Cells were imaged at 15 seconds intervals. Representative images of optoDroplet formation before and 6 minutes after light induction are shown. Quantifications from single-cell QIBC analysis of 2-3 independent experiments are shown with mean (solid line) and standard deviation from the mean (dashed lines) indicated.",
    "ncbi_link": "mCherry: 
Cry2: 839529
MDC1: 9656
53BP1: 7158"
  },
  {
    "caption": "Cry2-mCherry-53BP1 W1495A optoDroplet fusion at 15 seconds time resolution. Fusing optodroplets are highlighted by green arrowheads and in the magnified insets.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "Light-induced optoDroplet formation of the indicated Cry2-mCherry-53BP1 constructs. Cells were imaged at 15 seconds intervals. Representative images and quantifications of optoDroplet formation before and 6 minutes after light induction are shown. Quantifications from single-cell QIBC analysis of 2-3 independent experiments are shown with mean (solid line) and standard deviation from the mean (dashed lines) indicated. Red bars indicate the part of 53BP1 that was expressed as Cry2-mCherry fusion.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "Cry2-mCherry-53BP1 1203-1972 W1495A optoDroplets undergo fusion events upon light induction. Fusing optodroplets are highlighted by green arrowheads and in the magnified insets.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "Concentration-dependent optoDroplet formation exemplified by two neighboring cells that differ in their Cry2-mCherry-53BP1 1203-1972 W1495A expression level. Cells were imaged at 15 seconds intervals. Quantifications of optoDroplet formation in lowly expressing cells (mClow) and highly expressing cells (mChigh) from single-cell QIBC analysis of 3 independent experiments are shown with mean (solid line) and standard deviation from the mean (dashed lines) indicated.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "Cry2-mEGFP-53BP1 1203-1972 W1495A assembles into FokI-induced DNA repair compartments within seconds after light induction. FokI was induced for 1h where indicated before cells were light-activated and imaged at 15 seconds intervals. Red arrowheads mark the FokI-induced lesion with mCherry accumulation.",
    "ncbi_link": "mEGFP: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "Cry2-mCherry-53BP1 1203-1972 W1495A optoDroplets were induced as indicated and fixed 5 minutes later. Endogenous BRCA1 and p53 were co-stained.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "As in (A), comparing Cry2-mCherry-53BP1 constructs with and without the BRCT domains. Quantifications of p53 assembly into 53BP1 optoDroplets from single-cell QIBC analysis of 500-600 cells per condition are shown below with mean (solid line) and standard deviation from the mean (dashed lines) indicated. Red bars indicate the part of 53BP1 that was expressed as Cry2-mCherry fusion.",
    "ncbi_link": "mCherry: 
Cry2: 839529
53BP1: 7158"
  },
  {
    "caption": "qPCR of p21 induction upon DNA damage (10 Gy, 2h) with and without 0.4 M sorbitol. Mean ± standard deviation is indicated.",
    "ncbi_link": "p21: 1026"
  },
  {
    "caption": "A-B HT‑29 cells were transfected with non-silencing control siRNA (sictr) or siRNAs against USP22 (siUSP22) for 48 h at 20 nM. After transfection, cells were treated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα either for 6 h and analyzed by Western blotting (A) or for 18 h, and the percentage of PI-positive cells was assessed by fluorescence-based PI staining (B). Vinculin served as a loading control.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "C HT‑29 CRISPR/Cas9 control (ctr) and USP22 KO cells were analyzed by Western blotting for USP22 expression. GAPDH served as loading control.",
    "ncbi_link": "Cas9: 
CRISPR: 
USP22: 23326"
  },
  {
    "caption": "D HT‑29 control and USP22 KO cells were treated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα after pre-incubation with 30 µM Nec1-s and 20 µM GSK'872 for 1 h and incubated for 18 h before fluorescence-based quantification of PI-positive cells.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "E HT‑29 control and USP22 KO cells, generated with 2 guide RNAs (2g), expressing empty vector (EV) or PAM mutated 3xFLAG-HA-USP22 WT (USP22 PAM), C185S (USP22 PAM C185S) or C185A (USP22 PAM C185A) were analyzed by Western blotting for USP22 expression levels. β-Actin was used as a loading control.",
    "ncbi_link": "FLAG: 
HA: 
USP22: 23326"
  },
  {
    "caption": "F HT-29 control and USP22 KO cells, generated with 2 guide RNAs (2g), expressing empty vector (EV) or PAM mutated 3xFLAG-HA-USP22 WT (USP22 PAM), C185S (USP22 PAM C185S) or C185A (USP22 PAM C185A) were stimulated with 20 µM zVAD.fmk, 0.5 µM BV6, 1 ng/ml TNFα for 18 h. The percentage of PI-positive cells was assessed by fluorescence-based PI staining.",
    "ncbi_link": "FLAG: 
HA: 
USP22: 23326"
  },
  {
    "caption": "A HT‑29 control and USP22 KO cells were stimulated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα for the indicated time points. Detection of indicated proteins was carried out by Western blotting. GAPDH served as a loading control.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "B HT‑29 control and USP22 KO cells were stimulated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα for 4 h. Detection of indicated proteins was carried out by Western blotting. β-Actin served as a loading control.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "C HT‑29 control and USP22 KO cells were incubated with 30 µM Nec1-s or 20 µM Dab for 18 h, as indicated. Cell were stimulated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα for 5 h. 100 μg of each lysate were incubated with 400 U/μl λ-phosphatase for 30 min at 30 °C. Protein expression of RIPK3 was monitored by Western blotting. β-Actin was used as loading control. High molecular weight RIPK3 'smears' were quantified after λ-phosphatase treatment and normalized to total RIPK3 and β-Actin levels.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "A HeLa TRex RIPK3 CRISPR/Cas9 control (ctr) and USP22 KO cells were treated with 1 µg/ml Dox overnight. Protein expression of induced Strep-RIPK3 was analyzed by Western blotting. GAPDH served as loading control. The asterisk marks an unspecific band.",
    "ncbi_link": "Cas9: 
CRISPR: 
USP22: 23326"
  },
  {
    "caption": "B HeLa TRex RIPK3 control and USP22 KO cells were incubated with 1 µg/ml Dox for 18 h before pre-treatment with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα was added and cell death was measured after 4 and 5 h by analysis of PI-positive nuclei.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "C HeLa TRex RIPK3 control and USP22 KO cells were pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 1, 2, 3, 4 and 5 h. Protein expression of phosphorylated RIPK1, total RIPK1, total RIPK3, phosphorylated MLKL, total MLKL and USP22, without (left) or with (right) 1 µg/ml Dox treatment overnight, was monitored by Western blotting. GAPDH was used as a loading control.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "D HT-29 control cells and RIPK3 KO cells re-expressing PAM-mutated Dox-inducible RIPK3 WT were incubated overnight with 1 µg/ml Dox. Cells were pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 2 h, as indicated. Strep-RIPK3 was immunoprecipitated using anti‑Strep-beads and the indicated co-immunoprecipitated proteins were analyzed by Western blotting. β-Actin served as a loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "E USP22 KO HT-29 cells and USP22 KO cells re-expressing PAM-mutated 3xFLAG-HA-USP22 were pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα was added for 2 h, as indicated. 3xFLAG-HA-USP22 was immunoprecipitated using anti-HA-beads and the indicated co-immunoprecipitated proteins were analyzed by Western blotting. β-Actin served as a loading control.",
    "ncbi_link": "FLAG: 
HA: 
USP22: 23326"
  },
  {
    "caption": "A HT-29 control, USP22 KO and USP22 KO cells re-expressing PAM-mutated 3xFLAG-HA-USP22 WT or C185S were stimulated with 20 µM zVAD.fmk, 0.5 µM BV6 and 1 ng/ml TNFα for 4 h. Poly-ubiquitinated proteins were enriched by GST-TUBE pull-down, followed by incubation with the catalytic domain of USP2, as indicated. RIPK3 and USP22 expression and levels of ubiquitinated RIPK3 were monitored using Western blotting with the indicated antibodies. β-Actin served as loading control. Ponceau-staining was used to confirm equal loading of GST-TUBE.",
    "ncbi_link": "FLAG: 
HA: 
USP2: 9099
USP22: 23326"
  },
  {
    "caption": "B HT-29 control and USP22 KO cells were transfected with His-ubiquitin for 24 h, as indicated. Cells were pre‑stimulated with 20 µM zVAD.fmk, 0.5 µM BV6 for 1 h. Following pre-treatment, 1 ng/ml TNFα was added for 4 h. His-ubiquitin was immunoprecipitated using Ni-NTA beads and detection of indicated proteins was performed by Western blotting. β-Actin served as loading control for the input, whereas His-ubiquitin levels served as loading control for immunoprecipitated ubiquitin.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "C HeLa TRex RIPK3 control and USP22 KO cells were incubated with 1 µg/ml Dox and transfected with HA-ubiquitin for 24 h, as indicated. Cells were pre-stimulated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. Following pre-treatment, 10 ng/ml TNFα were added for 3 h. HA-ubiquitin was immunoprecipitated using anti-HA-beads and detection of indicated proteins was performed by Western blotting. β-Actin served as loading control for the input, whereas HA-levels served as loading control for immunoprecipitated ubiquitin.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "B Bar graphs demonstrating the number of up‐, non‐, and downregulated ubiquitination sites in USP22 KO HT-29 cells versus control under TBZ-treatment.",
    "ncbi_link": "USP22: 23326"
  },
  {
    "caption": "D HeLa cells expressing Dox-inducible RIPK3 WT, D160N, K42R, K351, K518R, 2xKR or 3xKR were pre‑incubated with 1 µg/ml Dox, 20 µM Dab, or 10 µM NSA overnight, followed by pre-treatment with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 4 h. Cell death was measured by quantification of PI-positive nuclei.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "E HeLa cells expressing Dox-inducible RIPK3 mutants were treated with 1 µg/ml Dox overnight. Protein levels of inducible RIPK3 expression were analyzed by Western blotting. GAPDH served as loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "A HeLa cells expressing Dox-inducible RIPK3 WT, K518R or 3xKR were treated with 1 µg/ml Dox and/or 10 µM NSA and 20 µM Dab overnight. Protein levels of inducible RIPK3 expression and phosphorylated MLKL were examined by Western blotting. β-Actin was used as a loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "B HeLa cells expressing Dox-inducible RIPK3 WT or 3xKR were treated with 1 µg/ml Dox overnight before pre-treatment with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 1, 2, 3 and 4 h. Protein levels of inducible RIPK3 expression and phosphorylated MLKL were analyzed by Western blotting. β-Actin served as loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "C HeLa cells expressing Dox-inducible RIPK3 WT, 2xKR or 3xKR were treated with 1 µg/ml Dox overnight before pre-treatment with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 2 h. Protein levels of inducible RIPK3 expression were analyzed by Western blotting. β-Actin served as loading control. D HeLa cells expressing Dox-inducible RIPK3 WT, K518R or 3xKR were treated with 1 µg/ml Dox overnight before pre-treatment with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 2 h. Whole cell lysates were generated using RIPA lysis buffer containing 2% SDS. Protein levels of inducible RIPK3 expression were analyzed by Western blotting. β-Actin served as loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "E HeLa cells expressing Dox-inducible RIPK3 WT, D160N, K518R or 3xKR were incubated overnight with 1 µg/ml Dox and pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 1 and 2 h. Strep-RIPK3 was immunoprecipitated by using anti-Strep-beads. Co-immunoprecipitated phosphorylated MLKL and RIPK1, as well as protein expression of indicated proteins were analyzed by Western blotting. β-Actin served as a loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "F HeLa cells expressing Dox-inducible RIPK3 WT, K518R or 3xKR were incubated with 1 µg/ml Dox and transfected with HA-ubiquitin for 24 h, as indicated. Cells were pre-treated with 20 µM zVAD.fmk, 5 µM BV6 for 1 h. After pre-treatment, 10 ng/ml TNFα were added for 2 h. HA-ubiquitin was immunoprecipitated using anti-HA-beads and detection of indicated proteins was performed by Western blotting. β-Actin served as loading control for the input, whereas HA-ubiquitin levels served as loading control for immunoprecipitated ubiquitin.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "A HT‑29 RIPK3 KO cells re-expressing Dox-inducible WT RIPK3 or the indicated RIPK3 mutants were incubated with 1 µg/ml Dox overnight. Cells were treated with 20 µM zVAD.fmk, 5 µM BV6 and 10 ng/ml TNFα for 4 h. Cell death was measured by analysis of PI-positive nuclei.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "B HT‑29 RIPK3 KO cells re-expressing Dox-inducible WT RIPK3 or the indicated RIPK3 mutants were incubated with 1 µg/ml Dox overnight, as indicated. Cells were treated with 20 µM zVAD.fmk, 5 µM BV6 and 10 ng/ml TNFα for 2 h and analyzed by Western blotting for RIPK3 and phosphorylated MLKL expression levels. β-Actin served as a loading control.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "(C) hematoxylin-eosin staining  with scale bar of 50 µm of the back skin   of ILEIind and K5-ILEIind mice  kept on normal or doxycycline  diet and treated with acetone  or TPA  for 5 days (n=2-5; 3 independent experiments).",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(D) mean epidermal  thickness ±SEM of the  back skin  of ILEIind and K5-ILEIind mice  kept on normal or doxycycline  diet and treated with acetone  or TPA  for 5 days (n=2-5; 3 independent experiments). Statistical significance was determined by one-way ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; ***p,0.001).",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(E) Representative images of ILEI immunohistochemistry  on sections of back skin  of ILEIind and K5-ILEIind mice  kept on normal or doxycycline  diet upon 5 days of treatment with acetone  or TPA. Scale bar 50 µm. Inlets show a magnification of the marked regions, scale bar 20 µm.",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(A) Representative images of Ki67 immunohistochemistry  on back skin  sections of K5-ILEIind and ILEIind mice  kept on normal or doxycycline  diet and treated with acetone  or TPA  for 5 days. Scale bar: 100 µm. (B) Percentage of Ki67  positive cells in the epidermis  shown as mean ±SEM and quantified on samples described in panel A (n=1-5; 3 independent experiments). Data information: Statistical significance was determined by one-way ANOVA (B at ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p,0.001).",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(D) Keratin 16 (K16)  western blot  analysis (left) and quantification (right) of proteins extracted from back skin  of ILEIind and K5-ILEIind mice  kept on doxycycline  and treated with acetone  or TPA  for 5 days (n=3). Vinculin  was used as loading control. Data information: Statistical significance was determined by one-way ANOVA at ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p,0.001).",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(G) Mean fold change in mRNA expression  ±SEM of K5  and K10  in primary keratinocytes  described in panel F (n=5-6; 2 independent experiments). Data information: Statistical significance was determined by two-way ANOVA (G) at ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p,0.001).",
    "ncbi_link": "K10: 16661
K5: 110308"
  },
  {
    "caption": "Mean fold change ±SEM in mRNA expression  of Tnfa, Il1α  and Cxcl1  (E) in freshly sorted keratinocytes  enriched for the inter-follicular epithelium (IFE) and hair follicles  (HF) from acetone  and TPA  treated back skin in mice  supplemented with doxycycline  and treated with acetone  or TPA  for 96 hours (n=3 (E), independent experiments). Data information: statistical significance was determined by one-way ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001). If significance levels were different for the pairwise comparisons with combined marking, asterisks, valid only for a subset of the pairs were put into brackets.",
    "ncbi_link": "Cxcl1: 14825
Il1α: 16175
Tnfa: 21926"
  },
  {
    "caption": "(G-I) Mean fold change ±SEM in mRNA expression  of (G) Tnfa, (H) Il1α  and (I) Cxcl1  in  primary keratinocytes treated with acetone  and TPA  and with increasing concentrations (100ng/ml, 250ng/ml, 500ng/ml, 1000ng/ml) of murine  recombinant ILEI  (mILEI) or dimerization-disabled ILEI   (mILEICA) or with empty-vector (empty) for 72 hours (n=3, standing for independent keratinocyte  cultures from three mice). Data information: statistical significance was determined by one-way ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001). If significance levels were different for the pairwise comparisons with combined marking, asterisks, valid only for a subset of the pairs were put into brackets.",
    "ncbi_link": "Cxcl1: 14825
Il1α: 16175
Tnfa: 21926"
  },
  {
    "caption": "(A-C) Representative images of (A) Phospho-STAT3  (Tyr727), (B) Phospho-Erk1/2 and (C) Phospho-Akt immunofluorescence  on thin sections of acetone  and TPA  treated back skin of  ILEIind and K5-ILEIind mice  kept on doxycycline  diet. Scale bar, 50 µm.",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(F) Western blot  analysis of STAT3  (Ser727 and Tyr705), Akt  and Erk1/2 phosphorylation  levels in primary Dox-induced K5-ILEIind keratinocytes  treated with acetone  or TPA  for 4 hours in the presence of the inhibitors STATTIC  (10µM), LY92004  (10µM) and UO126  (10µM). DMSO  was used as vehicle control. Vinculin  was used as loading control. Lanes are from non-continuous parts of the same gel.",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "(B) hematoxylin-eosin staining  with a scale bar of 50 µm and (C) mean epidermal  thickness ±SEM of the back skin  of ILEIfl/fl and ILEI∆Ep mice  treated with acetone  or TPA  for 5 days (n=3-8; 3 independent experiments). Data information: In C statistical significance was determined one-way ANOVA with Tukey multiple comparison test (C marked with asterisks (*p<0.05; **p<0.01; ****p<0.0001). If significance levels were different for the pairwise comparisons with combined marking, asterisks, valid only for a subset of the pairs were put into brackets.",
    "ncbi_link": "ILEI: 27999"
  },
  {
    "caption": "(F-H) (F) Representative images of MPO+ microabscesses   and neutrophils, (G) mean number ±SEM of MPO-positive microabsesses/cm skin  section and (H) mean number of neutrophils  (MPO+ cells)/mm2 epidermal-dermal  area ±SEM on thin sections of acetone  and TPA  treated back skin of ILEIfl/fl and  ILEI∆Ep mice  (n=6-8 (G) and n=2-8 (H); 3 independent experiments). Scale bar, 100 µm. Data information: In G and H, statistical significance was determined one-way ANOVA with Tukey multiple comparison test H) or by Student's t-test (G) and marked with asterisks (*p<0.05; **p<0.01; ****p<0.0001). If significance levels were different for the pairwise comparisons with combined marking, asterisks, valid only for a subset of the pairs were put into brackets.",
    "ncbi_link": "ILEI: 27999"
  },
  {
    "caption": "Mean fold change ±SEM in mRNA expression  of uPA  and uPAR  (D) in freshly sorted keratinocytes  enriched for the interfollicular epithelium from acetone  and TPA  treated back skin, (E) in primary keratinocytes isolated from ILEIind and K5-ILEIind mice, supplemented with doxycycline  and treated with acetone  or TPA  for 96 hours (n=3 (D), n=6 (E 1-2 independent experiments). Data information: In D,E Statistical significance was determined by one-way ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001).",
    "ncbi_link": "ILEI: 27999
K5: 281268
uPA: 18792
uPAR: 18793"
  },
  {
    "caption": "Mean fold change ±SEM in mRNA expression  of uPA  and uPAR  (F) in primary wild type keratinocytes  treated with acetone  and TPA  and with murine  recombinant wild type ILEI  (mILEI) for 8 and 96 hours n=6 F); 1-2 independent experiments). Data information: Statistical significance was determined by one-way ANOVA with Tukey multiple comparison test and marked with asterisks (*p<0.05; **p<0.01; ***p<0.001; ****p<0.0001).",
    "ncbi_link": "uPA: 18792
uPAR: 18793"
  },
  {
    "caption": "(L) ILEI Western blot  analysis of conditioned media harvested from  primary keratinocytes of ILEIind and K5-ILEIind mice  after 48-hours doxycycline  induction and treatment with TPA  and DMSO  or indicated concentrations of UK371804. Loading was normalized to cell count, numbers indicate relative intensities. Lanes are from non-continuous parts of the same gel.",
    "ncbi_link": "ILEI: 27999
K5: 281268"
  },
  {
    "caption": "B-G' Confocal images of the AIY labeled with synaptic vesicle marker GFP::RAB-3 (B-G, green) and active zone marker GFP::SYD-1 (B'-G', pseudo-red) in wild-type (B, B'), cwn-2(ok895) (C, C'), cfz-2(ok1201) (D, D'), pop-1(hu9) (E, E'), and sys-1 RNAi (G, G') animals. H-H' Quantification of the fluorescence intensity of AIY RAB-3 (H) and SYD-1 (H') for the indicated genotypes.",
    "ncbi_link": "cfz-2: 178768
cwn-2: 177870
pop-1: 171849
sys-1: 172859"
  },
  {
    "caption": "I-M' Confocal images of AIY labeled with mCherry::RAB-3 (pseudo-GFP) (I-M), or GFP::RAB-3 (I'-M') of tissue-specific RNAi treatment for control (I-I'), cwn-2(J-J'), cfz-2(K-K'), sys-1(L-L') and pop-1(M-M'). N-N' Quantification of the fluorescence intensity of AIY mCherry::RAB-3 or GFP::RAB-3 for the indicated RNAi treatment.",
    "ncbi_link": "cfz-2: 178768
cwn-2: 177870
pop-1: 171849
sys-1: 172859"
  },
  {
    "caption": "A Quantification of the fluorescence intensity of AIY GFP::RAB-3 in wild-type , egl-3(n589) and aex-5(sa23) mutants.",
    "ncbi_link": "aex-5: 173358
egl-3: 179412"
  },
  {
    "caption": "C Quantification of the fluorescence intensity of AIY GFP::RAB-3 for the indicated RNAi treatment. Candidates are intestinal expressed nlp or flp.",
    "ncbi_link": "flp: 182944"
  },
  {
    "caption": "Confocal images of AIY labeled with GFP::RAB-3 in wild-type (E) with a wild type nlp-40 transgene.",
    "ncbi_link": "nlp-40: 171591"
  },
  {
    "caption": "Confocal images of AIY labeled with nlp-40(tm4085) (F), nlp-40(vj3) (G), nlp-40(tm4085) (H) or nlp-40(vj3) (I) with a wild type nlp-40 transgene. J Quantification of the fluorescence intensity of AIY GFP::RAB-3 for the indicated genotypes. Transgenic data are averaged from at least two independent lines.",
    "ncbi_link": "nlp-40: 171591"
  },
  {
    "caption": "A-C Quantification of the fluorescence intensity of AIY presynaptic marker GFP::RAB-3 (A, B) and nlp-40 mRNA level (C) for the indicated genotypes. The AIY synaptic region was quantified for the synaptic intensity analysis.",
    "ncbi_link": "nlp-40: 171591"
  },
  {
    "caption": "D-I Confocal images of the transcriptional nlp-40 reporter (Pnlp-40::GFP) in wild-type (D), cwn-2(ok895) (E), cfz-2(ok1201) (F), pop-1(hu9) (G), and control or sys-1 RNAi (H and I) animals at adult Day 1 stage. J Quantification of the Pnlp-40::GFP fluorescence intensity for the indicated genotypes.",
    "ncbi_link": "GFP: 
cfz-2: 178768
cwn-2: 177870
nlp-40: 171591
pop-1: 171849
sys-1: 172859"
  },
  {
    "caption": "K-P Confocal images of an intestinal-specific reporter ERM-1::GFP in wild type (K), cwn-2(ok895) (L), cfz-2(ok1201) (M), pop-1(hu9) (N), and control or sys-1 RNAi (O and P) animals at the adult Day1 stage. Q Quantification of the ERM-1::GFP fluorescence intensity for the indicated genotype.",
    "ncbi_link": "cfz-2: 178768
cwn-2: 177870
pop-1: 171849
sys-1: 172859"
  },
  {
    "caption": "A Diagram of aex-2 genomic structure. The boxes and lines represent exons and introns. Black and gray indicate coding sequence and UTRs. The white asterisk marks the location of the R232Q mutation site of sa3 allele. B-K Confocal images of AIY presynaptic site labeled with GFP::RAB-3 in wild type(B), nlp-40(tm4085)(C), aex-2(sa3)(D), nlp-40(tm4085); aex-2(sa3) (E) over-expression NLP-40 in aex-2(sa3) mutants(F) and aex-2(sa3) with a wild-type aex-2 transgene driven by the endogenous promoter (Paex-2) (G), neuron-specific promoter (Prab-3) (H) , AIY-specific promoter (Pttx-3) (I) intestinal-specific promoter (Pges-1) (J) or muscle-specific promoter (Pmyo-3)(K). L-M Quantification of the fluorescence intensity of AIY GFP::RAB-3 for the indicated genotypes. Each dot represents one animal. Data were collected from at least three independent experiments. Transgenic data are averaged from at least two independent lines. tg: Paex-2::aex-2, Pttx-3::aex-2 or Pges-1::aex-2 transgene, +: wild type ; -: mutant or without tg. The AIY synaptic region was quantified for the synaptic intensity analysis.",
    "ncbi_link": "aex-2: 188491
ges-1: 178633
myo-3: 179676
nlp-40: 171591
NLP-40: 171591
rab-3: 173971
ttx-3: 181357"
  },
  {
    "caption": "N-Q' Confocal images of Paex-2::mNeonGreen of whole animal with bright field (N), the head region labeled with Paex-2::mNeonGreen and Pttx-3::mCherry with green channel (O), red channel (P) and the merged channels (Q). (O'-Q') are the cross sections corresponding to the dashed line sites.",
    "ncbi_link": "mCherry: 
mNeonGreen: 
aex-2: 188491
ttx-3: 181357"
  },
  {
    "caption": "A-A' Representative confocal images showing inactive (A) and active(A') state of AIY::GCaMP6s (with mod-1 promoter) colabeled with mCherry (with ttx-3 promoter) (red). Dashed ovals mark the AIY zone 2 region where GCaMP was quantified.",
    "ncbi_link": "mCherry: 
mod-1: 179269
ttx-3: 181357"
  },
  {
    "caption": "B-G Confocal images of Prab-3::GFP::RAB-3 in the nerve region corresponding to the dashed box in (A) of wild type (B), cwn-2(ok895) (C), cfz-2(ok1201) (D), pop-1(hu9) (E), nlp-40(tm4085) (F) and aex-2(sa3) (G) mutants. H-I Quantification of the GFP::RAB-3 intensity in the nerve ring synaptic region for the indicated genotypes. Each dot represents one animal. Data were collected from at least three independent experiments. Transgenic data are averaged from at least two independent lines.",
    "ncbi_link": "aex-2: 188491
cfz-2: 178768
cwn-2: 177870
nlp-40: 171591
pop-1: 171849"
  },
  {
    "caption": "G, Representative confocal images of NPC1, internalized integrin β1 and pFAK localization. Stably NPC1-GFP expressing cells were loaded with 2 μg/mL integrin β1 antibody for 30 min before fixation and  stained with pFAK antibody followed by secondary antibodies. Dashed line indicates the cell edge. H, Quantification of G using Mander's colocalization for the indicated markers. Mean ± SD, n = 5 cells. Cells were treated with 5 % LPDS for 1 day and then without (-) or with (+) 50 μg/ml  LDL for 1h. ",
    "ncbi_link": "GFP: 
NPC1: 4864"
  },
  {
    "caption": "F, Schematic outline for plasma membrane D4H labeling in combination with ORP2 degron system, and representative widefield epifluorescent images of co-plated cells after 4 h of LDL loading. Asterisk indicates ORP2-depleted degron cells. Dashed lines separate ORP2  expressing and depleted cells. G, Quantification of F. Mean ± SD, n = 20 fields of cells pooled from 2 independent experiments. Student's t-test. ",
    "ncbi_link": "ORP2: 9885"
  },
  {
    "caption": "A, Control and degron ORP2 cells were co-plated, and after 1 day incubation in 5 %  LPDS, cells were loaded with  LDL (+LDL) and IAA (+IAA; ORP2 depletion) for the indicated  times. Intracellular cholesterol was labeled with D4H  and imaged by widefield epifluorescence microscopy. Asterisk indicates region of ORP2-depleted cells. CM, complete medium. Dashed lines separate ORP2 expressing and depleted cells. B, Quantification of A. Mean ± SD, n = 15-27 cells pooled from 2 independent experiments. Student's t-test. ",
    "ncbi_link": "ORP2: 9885"
  },
  {
    "caption": "C, E, Control and degron ORP2 cells were co-plated, and after 1 day in 5 % LPDS, treated with 50 μg/ml LDL and IAA for the indicated times. Asterisk indicates an  ORP2-depleted cell. Double labeling of intracellular D4H and  Lamp1 (C) or intracellular D4H  and internalized integrin β1 (E). Images were acquired by confocal microscopy. Red box indicates a peripheral region toward the leading edge in the control cell, and blue box a corresponding region in the ORP2-depleted cell.",
    "ncbi_link": "ORP2: 9885"
  },
  {
    "caption": "B, Cells stably expressing NPC1-mCherry were treated with control or OCRL siRNAs for 2 days, or transfected with GFP-ORP2 or -ORP2-mHHK (PI(4,5)P2 binding-deficient mutant) for 1 day, stained with  PI(4,5)P2 antibody and imaged by confocal microscopy. For FAK  inhibition, GFP-ORP2 transfected cells were treated with 10 μM PF228 for 4 h. Dashed lines indicate cell edges. Arrowheads indicate colocalization of PI(4,5)P2  and NPC1. C, Quantification of B. Values from Ctrl siRNA and Vector control were pooled and are shown as Ctrl siRNA/Vector ctrl. Mean ± SD, n = 20-43 cells pooled from 2 independent experiments. Student's t-test. ",
    "ncbi_link": "GFP: 
mCherry: 
NPC1: 4864
OCRL: 4952
ORP2: 9885"
  },
  {
    "caption": "D, E, Cells stably expressing NPC1-mCherry were transfected with GFP-ORP2 or  GFP-ORP2-mHHK for 1 day and were indicated, treated with 10 μM PF228 for 4 h. For degron  ORP2  cells,  NPC1-mCherry was transiently transfected for 2 days and cells incubated without (-IAA; ORP2 present) or with IAA  (+IAA; ORP2 depleted) for 1 h. Arrowheads indicate tubular NPC1 organelles. Live cell images were acquired by widefield epifluorescence miroscopy and the longest  NPC1 tubule per cell was measured. Mean ± SD, n = 102-122 cells. Students's t-test. Please see also ctrl (MovieEV4) and PF228 treated cell (MovieEV5), both videos 1 min recordings with 1 s frame rate.",
    "ncbi_link": "GFP: 
mCherry: 
NPC1: 4864
ORP2: 9885"
  },
  {
    "caption": "A, B, Control and degron ORP2 cells were co-plated, and after 1 day 5 % LPDS, treated with 50 μg/ml LDL and  IAA (+IAA; ORP2 depletion) for the indicated  times and  immunostained for pFAK to quantify its intensity. For rescue experiments, degron ORP2 cells were plated and transfected with GFP-ORP2 or -ORP2-mHHK or -ORP2-∆ELSK for 6 h. Cells expressing GFP-ORP2 constructs at levels similar to endo-GFP-ORP2  were used for quantifying pFAK intensity. Dashed lines indicate cell outlines. See also Fig EV6C. Asterisk indicates cells depleted of endogenous  ORP2. Images were acquired by confocal microscopy. Mean ± SD, n = 20-23 cells pooled from 2 independent experiments. Student's t-test.",
    "ncbi_link": "GFP: 
ORP2: 9885"
  },
  {
    "caption": "C, Quantification of FAK protein in cytosolic and membrane fractions in degron ORP2 cells with or without IAA. Cells were starved overnight in LPDS and loaded with 50 µg/mL LDL +/- IAA for 2 h. The proportion of FAK signal in the membrane fraction (of total FAK in cytosol+membranes) is presented ± SD. For no IAA n=13 and for  IAA n= 11, 2 independent experiments. Student's t-test.",
    "ncbi_link": "ORP2: 9885"
  },
  {
    "caption": "(B) Schematic of marker-less GFP-tagging at the endogenous locus and representative  live cell  images of Mad1-, Mad2-, and Mad3-GFP   strains (average intensity projections).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(C) Representative images of  single molecule mRNA FISH  (smFISH) staining  of  S. pombe using probes against GFP  (red). DNA was stained  with DAPI  (blue). The gamma-value was adjusted to make the cytoplasm  visible; cell shapes are outlined in blue. (D) Frequency distribution of mRNA numbers per cell determined by smFISH; n = number of cells. Curves show fit to a Poisson distribution.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(E) Frequency distribution of mRNA numbers per cell using FISH  probes against the endogenous genes and using either strains expressing the GFP-tagged gene or the endogenous, untagged gene. Curves show fit to a Poisson distribution. The difference for mad1+ is statistically significant, that for mad2+ is not A lower mRNA number for untagged mad1+ was also observed in an independent strain.",
    "ncbi_link": "GFP: 
mad1: 2540320
mad2: 2540589"
  },
  {
    "caption": "(F) Co-staining  by smFISH  using probes against mad1+ and GFP  either in a strain expressing mad1+-GFP  as a positive control or in a strain expressing wild-type mad1+ and mad2+-GFP. Cytoplasmic mad1+ (green) or GFP  mRNA spots (magenta) were quantified as  co-localizing or not with the respective other. For the mad1+-GFP  strain, 544 cells and a total of 1,641 mad1  spots and 1,839 GFP  spots were analyzed; 48 cells were not considered since they did not contain at least one spot of each type in the cytoplasm. For the mad1+ mad2+-GFP  strain, 571 cells and a total of 1,107 mad1 spots and 1,537 GFP  spots were analyzed; 158 cells were not considered since they did not contain at least one spot of each type in the cytoplasm.",
    "ncbi_link": "GFP: 
mad1: 2540320
mad2: 2540589"
  },
  {
    "caption": "(D) mRNA abundances by qPCR  following metabolic labeling and removal of the labeled pool (two independent experiments). Lines are regression curves from generalized linear mixed model fits, excluding the measurements at t = 0 in order to accommodate for non-instantaneous labeling by 4tU. Act1+ and ecm33+ were used as long and short half-life controls, respectively; qPCR  was performed for the endogenous mRNAs. Half-lives (95 % confidence interval): mad1+ 5.6 min (4.3 - 8.4), mad2+ 7.7 min (6.2 - 10.4), mad3+ 5.2 min (4.3 - 6.9), act1+ 61.8 min (37.2 - 172.3), ecm33+ 5.0 min (4.5 - 5.7).",
    "ncbi_link": "Act1: 2540051
act1: 2540051
ecm33: 3361538
mad1: 2540320
mad2: 2540589
mad3: 2539219"
  },
  {
    "caption": "(A) The mean CSC  value for each S. pombe  gene (CSCg) relative to protein number per cell by mass spectrometry CSC  was determined using the mRNA half-life  data Colored dots highlight proteins of interest. For Mad2    and Bub1, no protein abundance data was available. (B) Cumulative frequency distribution of the CSCg  values for protein-coding  S. pombe  genes. The position of spindle assembly checkpoint genes is highlighted.",
    "ncbi_link": "Bub1: 2538736
Mad2: 2540589"
  },
  {
    "caption": "(D) Scatter plots of  whole cell RNA counts  versus cell length. Solid lines are regression curves from generalized linear mixed model fits (gray: wild type, black: codon-optimized or ste13∆). Dashed lines: 95 % bootstrap confidence bands for the regression curves. Model estimates of the ratio relative to wild-type mRNA are included with bootstrap 95 % confidence interval in brackets. Two to five replicates per genotype.",
    "ncbi_link": "ste13: 2541216"
  },
  {
    "caption": "(E) Time course  of RNA abundances by qPCR  following metabolic labeling and removal of the labeled pool (two independent experiments). Solid lines: regression curves from generalized linear mixed model fits (dark = ste13+, light = ste13∆), excluding t = 0 to accommodate for non-instantaneous labeling by 4tU. Shaded area: 95 % bootstrap confidence band for ste13+; dashed lines: 95 % bootstrap confidence band for ste13∆. Half-life  estimates are included with 95 % bootstrap confidence intervals in brackets.",
    "ncbi_link": "ste13: 2541216"
  },
  {
    "caption": "(A) Immunoblot  of S. pombe protein extracts from cells expressing wild-type (WT) or codon-optimized (co) Mad2-GFP  or Mad3-GFP  probed with antibodies against GFP  and Cdc2  (loading control). Lanes 3-5 are a 1:1 dilution series of the extract from cells expressing the codon-optimized version. (B) Immunoblot  of protein extracts from wild-type (WT) or ste13∆ strains probed with antibodies against Mad2, Mad3, and tubulin  (loading control). A 1:1 dilution series was loaded for quantification. (C) Estimates of the protein concentration relative to wild-type conditions from experiments such as in (A) and (B). Bars are experimental replicates, dots are technical replicates. Two-sided t-tests: p = 0.03 (Mad2-co), 0.004 (Mad3-co), 0.82 (Mad2 ste13∆), 0.15 (Mad3 ste13∆).",
    "ncbi_link": "GFP: 
Mad2: 2540589
Mad3: 2539219
ste13: 2541216"
  },
  {
    "caption": "(D) Whole-cell GFP   concentration from individual live cell fluorescence microscopy  experiments (a.u. = arbitrary units). Boxes show median and interquartile range (IQR); whiskers extend to values no further than 1.5 times the IQR from the first and third quartile, respectively. Codon-optimized concentration significantly higher than wild type for both genes (GLMM). Mad2-GFP: n = 468 and 413; Mad2-co-GFP: n = 206 and 366; Mad3-GFP: n = 224 and 127; Mad3-co-GFP: n = 160, 450 and 212 cells. (E) Representative images from one of the experiments in (D). A single Z-slice is shown. Cells are outlined in gray.",
    "ncbi_link": "GFP: 
Mad2: 2540589
Mad3: 2539219"
  },
  {
    "caption": "(B) Scatter plots of  whole cell mRNA counts versus cell length. Solid lines are regression curves from generalized linear mixed model fits (gray: wild type, black: codon-optimized or ste13∆). Dashed lines: 95 % bootstrap confidence bands for the regression curves. Model estimates of the ratio relative to wild-type mRNA are included with bootstrap 95 % confidence interval in brackets. Two to three replicates per genotype.",
    "ncbi_link": "ste13: 2541216"
  },
  {
    "caption": "(C)  Time course of RNA abundances by qPCR  following metabolic labeling and removal of the labeled pool (two independent experiments). Solid lines: regression curves from generalized linear mixed model fits (dark =  ste13+, light = ste13∆), excluding t = 0 to accommodate for non-instantaneous labeling by 4tU. Shaded area: 95 % bootstrap confidence band for ste13+; dashed lines: 95 % bootstrap confidence band for ste13∆. Half-life estimates are included with 95 % bootstrap confidence intervals in brackets.",
    "ncbi_link": "ste13: 2541216"
  },
  {
    "caption": "(D) Comparison between mean CSC  values for selected genes (CSCg) and  mRNA half-life   measured with or without deletion of ste13+.",
    "ncbi_link": "ste13: 2541216"
  },
  {
    "caption": "(A) Immunoblot  of S. pombe protein extracts from cells expressing wild-type (WT) or codon-optimized (co) Mad1-GFP  probed with antibodies against GFP  and Cdc2  (loading control). Lanes 3-5 are a dilution series of the extract from wild-type cells. (B) Immunoblot  of protein extracts from wild-type (WT) or  ste13∆ strains probed with antibodies against Mad1  and tubulin  (loading control). A 1:1 dilution series was loaded for quantification. (C) Estimates of the protein concentration relative to wild-type conditions from experiments such as in (A) and (B). Bars are experimental replicates, dots are technical replicates. Blue lines indicate the mean of all experiments. Two-sided t-tests: p = 0.005 (Mad1-co, n = 4 experimental replicates); p = 0.16 (Mad1 ste13∆, n = 2).",
    "ncbi_link": "GFP: 
Mad1: 2540320
ste13: 2541216"
  },
  {
    "caption": "(D) Whole-cell GFP  concentration from individual  live cell fluorescence microscopy experiments (a.u. = arbitrary units). Boxplots show median and interquartile range (IQR); whiskers extend to values no further than 1.5 times the IQR from the first and third quartile, respectively. Codon-optimized concentration significantly lower than wild type (generalized linear mixed model). Mad1-GFP: n = 197 and 224; Mad1-co-GFP: n = 80 and 377 cells. (E) Representative images from one of the experiments in (D). An average projection of three Z-slices is shown; cells are outlined in gray.",
    "ncbi_link": "GFP: 
Mad1: 2540320"
  },
  {
    "caption": "(F) Live-cell imaging for time  spent in mitosis. The  alp7+ gene was deleted to increase the likelihood of spindle assembly checkpoint activation. Localization  of Plo1-tdTomato  to  spindle pole bodies  was used to judge entry into and exit from mitosis   Exp1: n = 73 (WT) and 94 cells (co); Exp2: n = 126 (WT) and 152 cells (co). Boxplots show median and interquartile range (IQR); whiskers extend to values no further than 1.5 times the IQR from the first and third quartile, respectively. Measurements for individual cells are shown in addition (gray circles if measurement was exact, red triangles if end of mitosis   was not captured because imaging ended). Difference between WT and co: p = 0.14 (Exp1) and 0.15 (Exp2) by Kolmogorov-Smirnov test.",
    "ncbi_link": "alp7: 2543382"
  },
  {
    "caption": "(A) Top: Immunoprecipitation  (IP) with anti-GFP  or anti-Mad1  from extracts of haploid S. pombe cells expressing both untagged and GFP-tagged Mad1, probed with antibodies against Mad1  and tubulin; in = input (2.5 % of extract for IP), sup = supernatant after IP. Bottom: Comparison between the observed (obs.) and the expected (expect.) ratio between Mad1-GFP   and untagged Mad1   in the IP  given their ratio in the input ; two and one experiment(s), respectively. One more GFP-IP  from the same strain was unquantifiable, because no second band was visible in the IP.",
    "ncbi_link": "GFP: 
Mad1: 2540320"
  },
  {
    "caption": "(C) Top: Anti-GFP immunoprecipitation  (IP) and Strep pull-down (PD) from extracts of diploid cells expressing Mad1-GFP  and Mad1-Strep  from the two endogenous loci; membrane probed with anti-Mad1; in = input (7 % of extract for IP/PD), sup = supernatant after IP/PD. Bottom: as in (A), 2 experiments each. The experiment shown at the top and two more GFP-IPs  from the same strain were unquantifiable, because no second band was visible in the IP.",
    "ncbi_link": "GFP: 
Mad1: 2540320"
  },
  {
    "caption": "(E) Test for mRNA dimerization by  single molecule mRNA FISH; probes against mad1+ and GFP. Top: Schematic of genotypes. Bottom left: Intensity of cytoplasmic mad1+ mRNA spots in the different strains. For the 2 copy strain, a mad1+ spot was classified as mad1+-GFP if it was colocalizing   with a GFP  spot, and as mad1+ otherwise. Colors as indicated in the schematic. Vertical solid line: peak of each density plot; dashed line: theoretical position of a double-intensity peak. Number of spots analyzed: mad1+ (1 copy strain) = 921, mad1+ (2 copy strain) = 637, mad1+-GFP  (2 copy strain) = 982, mad1+-GFP  (1 copy strain) = 1699. Bottom right: Counts of cytoplasmic mad1+ or mad1+-GFP  mRNA from the same experiment with generalized linear mixed model fits as lines. Number of cells: 1 copy strain mad1+ = 478, 2 copy strain = 327, 1 copy strain mad1+-GFP  = 466.",
    "ncbi_link": "GFP: 
mad1: 2540320"
  },
  {
    "caption": "(F) Experiment similar to (E), except that cells expressing both mad1+-GFP  and mad3+-GFP  from the respective endogenous locus were probed with FISH  probes against mad1+ and GFP  mRNA. A GFP  spot was classified as mad1+-GFP  if it was colocalizing  with a mad1+ spot (arrowheads), and as mad3+-GFP  otherwise. The intensity of GFP  spots was quantified. Vertical solid line: peak of each density plot; dashed line: theoretical position of a double-intensity peak. Number of spots analyzed: mad1+-GFP  = 987, mad3+-GFP  = 1299.",
    "ncbi_link": "GFP: 
mad1: 2540320
mad3: 2539219"
  },
  {
    "caption": "Validation of GPRC5A western blot data using siRNA. *Non-specific band of ~60kDa not depleted by GPRC5A siRNA.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Basal & hypoxia-induced GPRC5A protein expression was decreased by HIF-1/2α depletion.",
    "ncbi_link": "2α: 2034
HIF-1: 3091"
  },
  {
    "caption": "Depletion of HIF-1β decreased GPRC5A protein upregulation in hypoxia.",
    "ncbi_link": "HIF-1β: 405"
  },
  {
    "caption": "Hypoxia mimetic DMOG induced HIF-1/2α, CA9 & GPRC5A protein expression. Dual HIF-1/2α depletion reduced GPRC5A induction by DMOG.",
    "ncbi_link": "2α: 2034
HIF-1: 3091"
  },
  {
    "caption": "qRT-PCR demonstrating that GPRC5A mRNA was upregulated by hypoxia. GPRC5A was normalised to HPRT (error bars ± SD).",
    "ncbi_link": "HPRT: 
GPRC5A: 9052"
  },
  {
    "caption": "qRT-PCR demonstrating that HIF-1/2α depletion decreased GPRC5A induction during hypoxia. GPRC5A was normalised to HPRT (error bars ± SD).",
    "ncbi_link": "HPRT: 
2α: 2034
GPRC5A: 9052
HIF-1: 3091"
  },
  {
    "caption": "ChIP/PCR analyses identify HIF-1α a binding to the GPRC5A promoter region containing a putative optimal HRE (error bars ± SD).",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Quantitative RT-PCR analysis of mouse intestinal tissue. Gene expression was normalised to housekeeping gene Tbp. Raw data from three independent experiments (n=3 mice) are shown (error bars ± SEM).",
    "ncbi_link": "Tbp: "
  },
  {
    "caption": "Tg[fli1:eGFP; vhl-/-] & Tg[fli1:eGFP] zebrafish embryos (5 days post-fertilisation) demonstrate excessive angiogenesis & increased expression of HIF target genes (scale bars: 100um).",
    "ncbi_link": "eGFP: 
vhl: 791202"
  },
  {
    "caption": "gprc5ba was induced in vhl mutant zebrafish embryos & fli1:eGFP zebrafish embryos exposed to 5% O2 (vs normoxia) for 24 hours (RT-PCR).",
    "ncbi_link": "eGFP: 
gprc5ba: 
vhl: 791202"
  },
  {
    "caption": "Kaplan-Meier curve following analysis of transcriptomics dataset GSE24551. Event-free survival is significantly reduced in patients with tumours expressing high levels of GPRC5A mRNA.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "GPRC5A depletion markedly increases caspase-3 activation/PARP cleavage during hypoxia.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Three independent siRNA sequences targeting GPRC5A induce caspase-3 activation/PARP cleavage during hypoxia.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "GPRC5A depletion reduces hypoxic cell growth/survival. Crystal violet cell assays show reduced cell growth/survival in GPRC5A depleted cells during hypoxia [n=3].",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Expression of an siRNA-resistant GPRC5A cDNA rescues hypoxic GPRC5A-depleted cells from apoptosis. Upper: doxycycline-induced expression GPRC5Asi1R rescues increases caspase-3/PARP cleavage induced by GPRC5A depletion in hypoxia. Lower: generation of an siRNA1 resistant GPRC5A cDNA by synonymous mutations.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Caspase inhibitor QVD prevents caspase-3 activation/PARP cleavage by GPRC5A depletion in hypoxia.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "GPRC5A depletion in hypoxia induces apoptosis as determined by the violet ratiometric membrane asymmetry probe/dead cell apoptosis assay and flow cytometry",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Hypoxia induced YAP stabilisation via Ser397 dephosphorylated was abrogated in GPRC5A depleted cells.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Hypoxia-induced nuclear localisation of YAP was attenuated in GPRC5A depleted cells.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Hypoxia activated TEAD activity (8x GTIIC-luc reporter) but this was reduced by GPRC5A depletion. A representative triplicate experiment is shown (n=3).",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Hypoxia reduced LATS activity and expression but this was prevented by GPRC5A depletion.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Constitutively active RhoA (G14V) expression restored YAP stabilisation (Ser397 dephosphorylation) by hypoxia in GPRC5A depleted cells.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "YAP knockdown was sufficient to induce caspase-3 activation/PARP cleavage in hypoxia and was not further enhanced by GPRC5A depletion.",
    "ncbi_link": "GPRC5A: 9052
YAP: 10413"
  },
  {
    "caption": "Crystal violet assays show that YAP was required downstream of GPRC5A to promote cell survival. GPRC5A depleted cells were rescued by expression of an siRNA-resistant GPRC5A cDNA (GPRC5Asi1R) but this was prevented by co-depletion of YAP (n=3 independent experiments).",
    "ncbi_link": "GPRC5A: 9052
YAP: 10413"
  },
  {
    "caption": "Expression of an siRNA-resistant GPRC5A rescued the critical phenotypes of GPRC5A depletion. GPRC5Asi1R expression prevented PARP cleavage in hypoxia as well as restoring hypoxia-induced YAP stabilisation (Ser397 dephosphorylation); these phenotypes were reversed by YAP depletion.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "GPRC5A depletion attenuated hypoxia-induced BCL-XL expression.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "Constitutively active YAP (S127A) expression induced BCL-XL expression and prevents caspase-3 activation/PARP cleavage by GPRC5A depletion in hypoxia.",
    "ncbi_link": "GPRC5A: 9052
YAP: 10413"
  },
  {
    "caption": "GPRC5Asi1R expression restored BCL-XL expression and prevents the appearance of cleaved caspase-3 induced by GPRC5A depletion in hypoxia.",
    "ncbi_link": "GPRC5A: 9052"
  },
  {
    "caption": "(C) Gene expression analysis of two NF-κB phases following damage. RNA-Seq analysis (n = 5 biological replicates per group) of U2-OS cells, either untreated or analyzed 1.5 hours or 7 days after irradiation (20 Gy), as indicated. The heatmap shows significantly regulated genes (log2 value > 0.5 and p value < 0.05). Black arrow points to NFKBIA. Significance determined by ANOVA with Bonferroni correction for multiple testing. See also Dataset EV1.",
    "ncbi_link": "NFKBIA: 4792"
  },
  {
    "caption": "(E) In situ hybridization using an anti-sense IκBα/Nfkbia riboprobe on longitudinal skin sections from male and female mice (5-8 weeks of age) treated as in (D) for the time indicated. Representative sections shown from n = 6 mice per condition. Bu, bulge region (dashed lines), HS, hair shaft, IFE, interfollicular epidermis. Scale bar: 50 μm. (F) Quantitation of (E) from n = 6 mice per condition and 3-4 sections per mouse. Bulge regions positive for Nfkbia were counted and presented as percentage of total. One way ANOVA analysis with Tukey multiple comparisons test was performed. SD shown. ** = p < 0.01. ",
    "ncbi_link": "Nfkbia: 4792
IκBα: 4792"
  },
  {
    "caption": "(B) NFKBIA knockdown by dox-inducible shRNA in U2-OS cells. Cells were pre-treated with Dox to induce knockdown. For knockdown efficiency see Fig. S2F. Cells were irradiated (20 Gy) or not, as indicated and described above. NF-κB activity was analyzed by EMSA. ns, non-specific band. A representative gel from n = 3 biological replicates is shown.",
    "ncbi_link": "NFKBIA: 4792"
  },
  {
    "caption": "(E) GSEA was performed comparing the IκBα IEC‐KO gene list (n = 4 villin-Cre x floxed IκBα mice and n = 4 littermate controls (GSE 139251) Mikuda et al, 2020(), with a gene signature based on a list of SASP factors Coppe et al, 2010(). NES: normalized enrichment score. FDR: false discovery rate.",
    "ncbi_link": "Cre: 2777477
IκBα: 18035
villin: 22349"
  },
  {
    "caption": "(F) RT-qPCR analysis of indicated genes was performed using RNA extracted from the duodenum of 5 and 8 weeks old control villin-Cre (n = 6) or villin-Cre x floxed IκBα mice (n = 6) both male and female. Expression is shown as fold change between littermates, paired t-test. SD shown. * p < 0.05 ** = P < 0.01.",
    "ncbi_link": "Cre: 2777477
IκBα: 18035
villin: 22349"
  },
  {
    "caption": "(B) Expression of SASP targets of NF-κB obtained from RNA-seq analysis (Dataset EV1B), was quantitated using RT-qPCR from the shRNA (RELA) stably expressing U2-OS cells. For knockdown efficiency see Appendix Fig S4A. Cells were treated with doxycycline (Dox) to induce knockdown of p65. Heatmap represents targets normalized to the untreated Scrambled control. Expression is shown as log2 change with p values < 0.05. Statistical analysis performed using ANOVA with Bonferroni correction for multiple testing. First-phase and second-phase samples were irradiated (20 Gy) 1.5h and 7 Days prior to harvest, respectively. Analysis based on n = 3 biological replicates.",
    "ncbi_link": "p65: 5970
RELA: 5970"
  },
  {
    "caption": "(C) Cell duplication was measured at time points indicated in U2-OS cells bearing either scrambled control or Dox-inducible shRNA against RELA (n = 3 biological replicates). Treatment with Dox was initiated at two days prior to IR (20 Gy) or after IR. Statistical significance in total duplication number between groups at day 6 was determined by ANOVA with Tukey multiple comparisons test. SD shown. * = P < 0.05, *** = p < 0.001.",
    "ncbi_link": "RELA: 5970"
  },
  {
    "caption": "(B) U2-OS cells treated with dox to deplete endogenous p65, were irradiated (20 Gy) and transfected with plasmids encoding p65, p65-S276A or p65-S468A, as indicated. Nuclear (N) and cytoplasmic (C) lysates were analyzed by SDS-PAGE at day seven post IR. Representative gel from n = 3 biological replicates is shown. PARP1 and αTubulin serve as fractionation and loading controls.",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "(C) ChIP performed with U2-OS cells irradiated (20 Gy) 1.5h or 7 days prior to assay, or left untreated (UT). Normalized relative enrichment of NFKBIA is shown (relative to input and two non-recruiting reference regions). Left panel: p65 antibody. n = 5 biological replicates with 3 technical repeats per biological replicate. Right: Antibody against p65 pSer468. n = 2 biological replicates with three technical repeats per biological replicate. Statistical significance was determined by ANOVA with Tukey multiple comparisons test. SD shown. * = p < 0.05, ** = p < 0.01, *** = p < 0.001",
    "ncbi_link": "NFKBIA: 4792"
  },
  {
    "caption": "(E) U2-OS cells left untreated (ut) or irradiated (20 Gy) 7 days before harvesting, as indicated. Two days prior to harvest cells were transfected with siRNA against GSK3β or scrambled control (Scr). Whole cell lysates were analyzed by SDS-PAGE and western blotting. A representative example from n = 3 experiments is shown.",
    "ncbi_link": "GSK3β: 2932"
  },
  {
    "caption": "(C) U2-OS cells transfected with TRAF6 siRNA or scrambled control siRNA and TRAF6 and IKKβ levels analyzed by western blotting (top panels). NF-κB activity was determined by EMSA in untreated cells (ut) and after IR at indicated time points (lower panel). ns, unspecific band. Representative gels are shown from n = 2 biological replicates.",
    "ncbi_link": "TRAF6: 7189"
  },
  {
    "caption": "(E) U2-OS CRISPR IKBKB knockout and control cell lines were irradiated (20 Gy) and harvested at indicated time points. NF-κB activity was analyzed by EMSA (lower panel). ns indicates an non-specific band. Upper panel, western blot analysis of actin and IKKβ. Representative gels shown from n = 3 replicates.",
    "ncbi_link": "IKBKB: 3551"
  },
  {
    "caption": "(F) Irradiated U2-O2 control and IKBKB knockout cells (as above) were analyzed by RT-qPCR at the time points indicated for expression of NF-κB target genes identified by RNA-Seq (Dataset EV1). Significantly regulated targets, cutoff set at p = 0.05 (as determined by ANOVA with Tukey multiple comparison), are shown.",
    "ncbi_link": "IKBKB: 3551"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNA encoding dkk1 (35/45 pg) protein. Total RNA was isolated from ten control embryos at neurula stage 17 (lane 2) and ten embryos from each dkk1 injected group (lanes 3-4). Various neural AP markers were examined by sqRT-PCR: cement gland and forebrain (xag1, xanf1, otx2), hindbrain (krox20, hoxb3), hindbrain/spinal cord border (hoxb4), and spinal cord (hoxb9, cdx1-2-4, hoxd10). Ef1α serves as a control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "Ef1α: 
xag1: 397989///379354
cdx1: 108710769///397695
dkk1: 22943
krox20: 378520
xanf1: 397950
hoxb3: 373719
hoxb4: 734796
hoxb9: 108700809///100381079
hoxd10: 399032
otx2: 432013///399342"
  },
  {
    "caption": "One-cell stage embryos were injected animally with the zygotic-expressing Nxfz8/pCS2 encoding plasmid (100/200 pg). Total RNA was isolated from ten control embryos at neurula stage 17 (lane 2) and ten embryos from each Nxfz8 injected group (lanes 3-4). Various neural AP markers were examined by sqRT-PCR: cement gland and forebrain (xag1, xanf1, otx2), hindbrain (krox20, hoxb3), hindbrain/spinal cord border (hoxb4), and spinal cord (hoxb9, cdx1-2-4, hoxd10). Ef1α serves as a control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "Ef1α: 
xag1: 379354///397989
cdx1: 397695///108710769
krox20: 378520
Nxfz8: 399367
xanf1: 397950
hoxb3: 373719
hoxb4: 734796
hoxb9: 108700809///100381079
hoxd10: 399032
otx2: 399342///432013"
  },
  {
    "caption": "Embryos from the same experiment as in (A) underwent in situ hybridization. Expression of the hindbrain marker krox20 (upper two panels) was reduced by Dkk1 (45pg) in 83% of the embryos (n=18). Expression of spinal cord markers (hoxb9, cdx4, hox10) was normal, being unchanged in 89% of the embryos (n=18 for each marker). Control embryos, (CE).",
    "ncbi_link": "krox20: 
cdx4: 380412///108700082
Dkk1: 22943
hoxb9: 108700809///100381079
hox10: 108703009///399032"
  },
  {
    "caption": "One-cell stage embryos were injected animally with the Zic1-MO (25/40 ng). Total RNA was isolated from ten control embryos at neurula stage 18 (lane 2) and ten embryos from each Zic1-MO injected group (lanes 3-4). Neural AP markers were examined by sqRT-PCR: forebrain (xanf1, otx2), hindbrain (krox20, hoxb1, hoxb3), spinal cord (hoxb9, cdx1-4) and panneural (soxd). Ef1α is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "Ef1α: 
cdx1: 397695///108710769
krox20: 378520
xanf1: 397950
hoxb1: 100301962///108702519
hoxb3: 373719
hoxb9: 100381079///108700809
otx2: 432013///399342
soxd: 397708
Zic1: 399124"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNA encoding Zic5 dominant-negative (0.5 ng) protein. Total RNA was isolated from five control embryos at neurula stage 18 (lane 1) and five embryos from the injected group (lanes 2). Neural AP markers were examined by sqRT-PCR: hindbrain (krox20) and spinal cord (cdx1-4). Ef1α is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 3).",
    "ncbi_link": "Ef1α: 
cdx1: 397695///108710769
krox20: 378520
Zic5: 108708473///373661"
  },
  {
    "caption": "One-cell stage embryos were injected animally with the Zic1-MO (25 ng). Embryos underwent in situ hybridization. Expression of the panneural sox2 marker was normal, the forebrain marker xanf1 was expanded in 80% of the embryos, the hindbrain representative marker krox20 was reduced in 80% of the embryos and the representative spinal cord marker cdx4 was expanded in 90% of the embryos. N = 23 embryos were per marker.",
    "ncbi_link": "Zic1: 399124"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNAs encoding the noggin (5/20 pg) and/or meis3 (0.5 ng) proteins. AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to neurula stage 17. Total RNA was isolated from seven control embryos (lane 2), and from eighteen ACs from each group (lanes 3-8). Neural AP markers were examined by sqRT-PCR: forebrain (xanf1, otx2), hindbrain (krox20, hoxb1, hoxb3), spinal cord (hoxb9, cdx1-4) and panneural (soxd). Ef1α is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "Ef1α: 
cdx1: 397695///108710769
krox20: 378520
xanf1: 397950
hoxb1: 100301962///108702519
hoxb3: 373719
hoxb9: 100381079///108700809
meis3: 379219///398093
noggin: 108704141///373646
otx2: 399342///432013
soxd: 397708"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNA encoding bmp4 (0.2 ng) protein. Total RNA was isolated from five control embryos at neurula stage 17 (lane 1) and five embryos from the injected group (lanes 2). Neural and mesodermal markers were examined by sqRT-PCR: forebrain (otx2), hindbrain (krox20, hoxb3), spinal cord (hoxb9, hoxc10, cdx4), panneural (nrp1, ncam) and mesodermal (muscle actin - MA). ODC is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "ODC: 
bmp4: 397874///399322
cdx4: 108700082///380412
krox20: 378520
hoxb3: 373719
hoxb9: 100381079///108700809
hoxc10: 399206
MA: 108706299
muscle actin: 108706299
ncam: 397761///397762
nrp1: 397804
otx2: 399342///432013"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNA encoding bmp4 (0.2 ng) protein Embryos underwent in situ hybridization. Expression of the hindbrain marker hoxb3 was reduced/eliminated by bmp4 (0.2 ng) in 68% of the embryos (n=19). Expression of the spinal cord marker cdx4 was slightly increased/normal, in 100% of the embryos (n=19).",
    "ncbi_link": "bmp4: 397874///399322"
  },
  {
    "caption": "One-cell stage embryos were injected animally with increasing concentrations of bmp4 encoding mRNA (5-50 pg). AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to neurula stage 16. Total RNA was isolated from five control embryos (lane 2), and from eighteen ACs from each group (lanes 3-7). Neural, epidermal and mesodermal markers were examined by sqRT-PCR: hindbrain (krox20), spinal cord (hoxb9, hoxc10/d10, cdx1-2-4), epidermal cytokeratin (E13), lateral mesoderm (osr1-2) and dorsal-lateral mesoderm muscle actin (MA). ODC is the control for quantitating the RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "ODC: 
bmp4: 397874///399322
cdx1: 397695///108710769
krox20: 378520
hoxb9: 108700809///100381079
hoxc10: 399206
d10: 399032
cytokeratin (E13): 379143
MA: 108706299
muscle actin: 108706299
osr1: 100313967"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNAs encoding the bmp4 (50/150 pg) and/or meis3 (0.7 ng) proteins. AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to neurula stage 16. Total RNA was isolated from five control embryos (lane 2), and from eighteen ACs from each group (lanes 3-8). Neural and mesodermal markers were examined by sqRT-PCR: hindbrain (krox20), spinal cord (hoxb9, hoxc10, cdx2), and lateral mesoderm (osr1). Ef1α is the control for quantitating the RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "Ef1α: 
bmp4: 397874///399322
cdx2: 735025///397753
krox20: 378520
hoxb9: 108700809///100381079
hoxc10: 399206
meis3: 379219///398093
osr1: 100313967"
  },
  {
    "caption": "One-cell stage embryos were injected animally with increasing concentrations of bmp4 encoding mRNA (75-200 pg). AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to gastrula stage 11-11.5. Total RNA was isolated from five control embryos (lane 2), and from eighteen ACs from each group (lanes 3-6). Marker expression was determined by sqRT-PCR. Xenopus brachyury (xbra) expression was induced by BMP4 in a dose-dependent manner. Marker expression was determined by sqRT-PCR. Neither dorsal (chd, goosecoid-gsc) or ventral-lateral (osr1) mesoderm markers were induced by BMP4. Sox2/3 neural markers are expressed in the ACs and are unchanged by BMP expression. EF1α is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "EF1α: 
bmp4: 397874///399322
BMP4: 397874///399322
BMP: 399322
chd: 733207
goosecoid: 397748///397752
gsc: 397748///397752
osr1: 100313967
Sox2: 398000
Xenopus brachyury: 399275
xbra: 399275"
  },
  {
    "caption": "One-cell stage embryos were injected animally with increasing concentrations of bmp4 encoding mRNA (5-50 pg). AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to neurula stage 16. Total RNA was isolated from five control embryos (lane 2), and from eighteen ACs from each group (lanes 3-6). FGF3-4-8 expression was determined by sqRT-PCR. ODC is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "bmp4: 
ODC: 
FGF3: 108715251///373669"
  },
  {
    "caption": "One-cell stage embryos were injected animally with mRNAs encoding the bmp4 (50 pg) and/or FGF dominant-negative receptor (FGF-DNR, 1.5 ng) proteins. AC explants were removed from control and injected embryos at blastula stage 9, and explants were cultured to neurula stage 16. Total RNA was isolated from five control embryos (lane 2), and from eighteen ACs from each group (lanes 3-6). In addition to fgf3, neural, epidermal and mesodermal markers were examined by sqRT-PCR: hindbrain (krox20, hoxb3), spinal cord (hoxb9, hoxc10, cdx4), lateral mesoderm (osr1), dorsal-lateral mesoderm muscle actin (MA), and epidermal cytokeratin (E13). ODC is the control for quantitating RNA levels. -RT-PCR was performed on total RNA isolated from control embryos (lane 1).",
    "ncbi_link": "bmp4: 
ODC: 
cdx4: 108700082///380412
krox20: 378520
fgf3: 108715251///373669
FGF: 394418
hoxb3: 373719
hoxb9: 100381079///108700809
hoxc10: 399206
cytokeratin (E13): 379143
MA: 108706299
muscle actin: 108706299
osr1: 100313967"
  },
  {
    "caption": "Representative BLI traces showing decreased binding of Nxph1 to the Nrxn1 LNS2SS2- (I401Q) mutant compared to that of wild-type Nrxn1 LNS2SS2-. Replicate numbers are shown in E.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "Representative BLI traces showing increased binding of Nxph1 to Nrxn1 LNS2SS2A+ and Nrxn1 LNS2SS2AB+ compared to that of Nrxn1 LNS2SS2-. Replicate numbers are shown in E.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "Comparison of binding affinities for Nxph1 binding to mouse Nrxn1 LNS2 splice variants and splice-insert containing Nrxn1 LNS2 with the I401Q mutation; error bars represent SEM and replicate numbers are indicated in or above bars. Significance values were calculated using Welch's t-test, *P < 0.05, **P < 0.01, ****P < 0.0001.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "Comparison of binding affinities of Nxph1 for Nrxn1 LNS2SS2- and Nrxn1 LNS2SS2A+ with or without Ca2+ added; replicate numbers are indicated in bars. Error bars represent SEM, and significance values were calculated using Welch's t-test. ns, not significant.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "C. Representative images of calyx synapses from littermate control and Nrxn123 TKO mice. Brainstem sections were labeled with antibodies to vGluT1 (red) and Syt2 (green). Scale bar, 10 μm. D. Summary graphs of the synaptic vGluT1 and Syt2 immunostaining intensity (normalized to control). ",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "E-H. Representative traces of spontaneous EPSCs (sEPSCs)(E), and summary graphs of the sEPSC frequency (F), amplitude (G), and kinetics (H) recorded from littermate control and Nrxn123 TKO mice.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "A. Representative traces of EPSCs evoked by paired stimuli separated by 10 ms and repeated every 20 s, recorded in a standard bath solution containing 2 mM Ca2+. B. Pan-neurexin deletion suppresses synaptic transmission. Summary graphs show the amplitude (left) and charge transfer (right) of the first EPSC recorded in response to the paired stimuli. C. Pan-neurexin deletion more than doubles the paired-pulse ratio (PPR), suggesting a large decrease in release probability. D. Pan-neurexin deletion decelerates the EPSC time course. Summary graphs show the rise time (left) and decay time constants (right) of the first EPSC in response to the paired stimuli. ",
    "ncbi_link": "neurexin: 18191///18190///18189"
  },
  {
    "caption": "E-F. Pan-neurexin deletion does not significantly alter the cumulative EPSC amplitude during a high-frequency stimulus train (100 Hz for 0.5 sec). Left, representative ESPC traces; right, cumulative summary plot of the EPSC amplitudes during the train (dotted lines show linear regression fits for estimating the cumulative EPSC amplitude by back-extrapolation to zero time, which is used to correct for vesicle replenishment during the train).",
    "ncbi_link": "neurexin: 18191///18190///18189"
  },
  {
    "caption": "G. Pan-neurexin deletion does not decrease the readily-releasable pool of vesicles, but lowers the initial release probability during a high-frequency stimulus train. Summary graphs show the cumulative EPSC amplitudes extrapolated to time zero as an estimate of the readily-releasable pool size (left), and the ratio of the first EPSC amplitude divided by the cumulative EPSC amplitudes extrapolated to time zero as an estimate of the initial release probability (right).",
    "ncbi_link": "neurexin: 18191///18190///18189"
  },
  {
    "caption": "F. Summary graph of the relative contribution of P/Q-type Ca2+ channels to the total presynaptic Ca2+ currents, as quantified by the relative reduction in Ca2+ currents evoked by step depolarization to +10 mV, in control and Nrxn123 TKO synapses.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "A. Representative traces of Ca2+-currents and 4-AP insensitive K+-currents evoked by step depolarizations (from −50 mV to +10 mV in 10 mV increments), recorded from the calyx terminals in acute slices from littermate control and Nrxn123 TKO mice at P12-P14. B. Same as (A) but after addition of 200 nM iberiotoxin (IbTx) by perfusion. C. Representative traces of presynaptic BK currents , which are calculated by subtracting currents shown in (B) from currents shown in (A). D. Summary graphs of the capacitance, Ca2+-current density, and BK-current density. ",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "A. Representative images of brainstem cryosections stained by triple immunofluorescence labeling for vGluT1 (green), CaV2.1-type Ca2+-channels (red), and the active zone protein Bassoon (purple). Cryosections were obtained from littermate control and Nrxn123 TKO mice at P12-14. Scale bar, 10 μm.",
    "ncbi_link": "Nrxn1: 18189"
  },
  {
    "caption": "(B, C) Body weight of the WT and L-HRD KO mice at the age of 12 weeks. (n=5 for each group) Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD: 74126"
  },
  {
    "caption": "(D) Body heights and tibia lengths of the WT and L-HRD KO mice. (n=5 for each group) Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD: 74126"
  },
  {
    "caption": "(E) Phosphorylation of STAT5 in WT and HRD1 LKO liver.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(E) Hepatic growth hormone signaling target genes mRNA levels in the WT and L-HRD1 KO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.).",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "Hepatic growth hormone signaling target genes mRNA levels in the WT and L-HRD1 KO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(A) Volcano plot of differential genes between WT and HRD1 LKO livers.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(B) Hepatic Fgf21 mRNA in the WT and L-HRD1 KO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "Fgf21: 56636
HRD1: 74126"
  },
  {
    "caption": "(C) Serum FGF21 protein levels in the WT and L-HRD1 KO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(D) Correlation analysis of the gene expression (Red: Upregulated genes and Blue: Downrelated genes) between HRD1 LKO mice and FGF21 transgenic mice.",
    "ncbi_link": "FGF21: 56636
HRD1: 74126"
  },
  {
    "caption": "(E) Percentage of mated with proven stud males and age at onset of puberty in the female WT and L-HRD KO mice. (n=10 for each group) Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD: 74126"
  },
  {
    "caption": "(F) Examples of ovarian histology from WT and HRD1 LKO mice.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(G) Representative examples of estrus cycles in WT and L-HRD1 KO mice as determined by vaginal cytology.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(I) H&E stain of white adipose tissue WT and HRD1 LKO mice 14 weeks after HFD feeding.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(J) Ucp1 and Dio2 mRNA levels of adipose tissue from (I) (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "Dio2: 13371
Ucp1: 22227"
  },
  {
    "caption": "(B) Volcano plot of differential proteins between WT and HRD1 LKO livers.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(F) Protein levels of IRE1α, NRF1, RXRβ, NOTCH1, SIRT3 and GAPDH in the liver of WT and HRD1 LKO mice under the refed condition. (n=6 for each group).",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "Hepatic CREBH protein levels in the WT and L-HRD1 KO mice. (n=6 for each group).",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "Hepatic CREBH mRNA (B) levels in the WT and L-HRD1 KO mice. (n=6 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.).",
    "ncbi_link": "CREBH: 208677
HRD1: 74126"
  },
  {
    "caption": "(C) Western Blot analysis CREBH protein stability after HRD1 over-expression. Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD1: "
  },
  {
    "caption": "(D) Western Blot analysis of hepatic CREBH and HRD1 protein levels in WT and HRD1 LKO mice. The mice were fasted 16 hours and refed for another 4 hours.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(H) Hepatic CREBH ubiquitination level in the WT and L-HRD1 KO mice",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(J) Primary hepatocytes were isolated from WT and HRD1 LKO mice and Western Blot analysis CREBH protein stability.",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(C, D) Ubiquitination of CREBH and CREBH K294R were measured after co-transfected C-terminal of HRD1.",
    "ncbi_link": "HRD1: 
CREBH: 84699"
  },
  {
    "caption": "(E) Western Blot analysis CREBH or CREBH-K294R protein stability after HRD1 protein over-expression. Data information: The data are representative of three independent experiments (mean ± s.d.",
    "ncbi_link": "CREBH: 84699"
  },
  {
    "caption": "(F) Western Blot analysis of the CREBH WT or K48 only ubiquitination level after HRD1 C-terminal co-expression.",
    "ncbi_link": "HRD1: 
CREBH: 84699"
  },
  {
    "caption": "(H) Western Blot analysis of the CREBH K6, K11, K27, K29 and K33 only ubiquitination level after HRD1 co-expression.",
    "ncbi_link": "HRD1: 
CREBH: 84699"
  },
  {
    "caption": "(I) Western Blot analysis of the CREBH WT, K27R ubiquitination level after HRD1 full-length co-expression.",
    "ncbi_link": "HRD1: 
CREBH: 84699"
  },
  {
    "caption": "(J) Western Blot analysis of the CREBH WT, K27 and K48 only ubiquitination level after HRD1 C-terminal co-expression.",
    "ncbi_link": "HRD1: 
CREBH: 84699"
  },
  {
    "caption": "(C) Hepatic Fgf21 mRNA in the WT and L-HRD1 KO mice 5 weeks after AAV-shCrebh injection. (n=5 for each group).",
    "ncbi_link": "Fgf21: 56636
HRD1: 74126"
  },
  {
    "caption": "(D) Serum FGF21 protein levels in the WT and L-HRD1 KO mice 5 weeks after AAV-shCrebh injection. (n=5 for each group).",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(E) Body height and tibia length of the WT and L-HRD1 KO mice 5 weeks after AAV-shCrebh injection (n=5 for each group).",
    "ncbi_link": "HRD1: 74126"
  },
  {
    "caption": "(F) Hepatic Igf1, Cyp2d9 and Cyp4a12 mRNA in the WT and L-HRD1 KO mice 5 weeks after AAV-shCrebh injection. (n=5 for each group).",
    "ncbi_link": "Cyp2d9: 13105
Cyp4a12: 277753///13118
Igf1: 16000
HRD1: 74126"
  },
  {
    "caption": "(G, H) Percentage of the mated and estrus cycle of the WT and L-HRD KO 5 weeks after AAV-shCrebh injection. Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "HRD: 74126"
  },
  {
    "caption": "(A) Examples of the body sizes of the WT, L-HRD KO and HRD1/FGF21 DKO mice. (B, C) Body weight and body height of the WT, L-HRD KO and HRD1/FGF21 DKO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "FGF21: 56636
HRD: 74126
HRD1: 74126"
  },
  {
    "caption": "(D) Tibia lengths of the WT, L-HRD KO and HRD1/FGF21 DKO mice fed with normal chow diet. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "FGF21: 56636
HRD: 74126
HRD1: 74126"
  },
  {
    "caption": "(E) Hepatic Hsd3b5, Cyp2d9 and Cyp4a12 mRNA in the WT, L-HRD1 KO and HRD1/FGF21 DKO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "Cyp2d9: 13105
Cyp4a12: 277753///13118
FGF21: 56636
Hsd3b5: 15496
HRD1: 74126"
  },
  {
    "caption": "(F) Estrus cycle of L-HRD KO and HRD1/FGF21 DKO mice at the age of 4 months. Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "FGF21: 56636
HRD: 74126
HRD1: 74126"
  },
  {
    "caption": "(G) Percentage of the Activity, feeding and water intake of the WT, L-HRD KO and HRD1/FGF21 DKO mice. (n=5 for each group). Data information: The data are representative of three independent experiments (mean ± s.d.). *: P<0.05. **: P<0.01 by unpaired student's t test.",
    "ncbi_link": "FGF21: 56636
HRD: 74126
HRD1: 74126"
  },
  {
    "caption": "(D,E) Pharmacological inhibition (for example, 3‐methyladenine (3‐MA), 10 mM) or genetic deletion (for example, ATG5−/−) of the autophagy pathway decreases the protein and mRNA expression of UVRAG and increases apoptosis at 12 h in HL60 cells treated with doxorubicin (Doxo) and UV irradiation (n=3, *P0.05). AU, arbitrary units; C‐PARP, cleaved poly‐ADP ribose polymerase; LC3, light chain 3; mRNA, messenger RNA; PI, propidium iodide; UV, ultraviolet; UVRAG, ultraviolet irradiation resistance‐associated gene.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(E) After transfection with UVRAG shRNA or control shRNA for 48 h, ATG5+/+ and ATG5−/− murine embryonic fibroblasts (MEFs) were treated with doxorubicin (1 μg/ml), with or without Z‐VAD‐FMK (20 μM) for 12 h, and then apoptosis was assayed (n=3, *P0.05).",
    "ncbi_link": "ATG5: 11793
UVRAG: 78610"
  },
  {
    "caption": "(F) Nude mice were inoculated with 4 × 106 HL60 tumour cells following transfection of control (shControl) or UVRAG (shUVRAG)‐specific shRNA and treated with doxorubicin (10 mg/kg) beginning at day 7. Tumours were measured twice weekly, and volumes were calculated for 21 days (n=10, *P0.05; shControl+Doxo compared with shUVRAG+Doxo).",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(A) Control shRNA or UVRAG shRNA cells were transfected with BAX plasmid, and apoptosis was assayed (n=3, *P0.05).",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(C) After transfection with UVRAG vector or control vector for 48 h, cells were transected or treated with BAX (1 μg), BAD (1 μg), BID (1 μg), FAS antibody (10 μg/ml) or TRAIL (100 ng/ml) for 24 h, then cell apoptosis was analysed (n=3, *P0.05).",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(D) Knockdown of UVRAG in BAX−/− HCT116 cells restored the sensitivity to UV treatment‐induced apoptosis (n=3, *P0.05). AU, arbitrary units; BAX, BCL2‐associated X protein; shRNA, short‐hairpin RNA; UV, ultraviolet; UVRAG, ultraviolet irradiation resistance associated gene.",
    "ncbi_link": "BAX: 581
UVRAG: 7405"
  },
  {
    "caption": "(D) UVRAG C2 domain deletion terminates BAX binding. HCT116 cells were transfected with Flag‐UVRAG or its mutants (ΔC2, ΔCCD), and then assayed for protein expression levels as indicated by IP or western blot.",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "(E) Apoptosis was assayed in indicated HCT116 cells after treatment with doxorubicin (Doxo, 1 μg/ml), UV irradiation (5 min after 50 mJ/cm2) or transfected with BAX (1 μg) for 24 h. BAX, BCL2‐associated X protein; CCD, coiled‐coil domain; CHAPS, 3‐[(3‐cholamidopropyl)‐dimethylammonio]‐1‐propane sulphonate; GST, glutathione‐S‐transferase; IB, immunoblotting; IgG, immunoglobulin G; IP, immunoprecipitation; RIPA, radioimmunoprecipitation assay; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; UV, ultraviolet; UVRAG, ultraviolet irradiation resistance associated gene.",
    "ncbi_link": "BAX: 581
UVRAG: 7405"
  },
  {
    "caption": " UVRAG inhibits mitochondrial translocation of BAX. After transfection with indicated shRNA or cDNA for 48 h, HL60 cells were treated with doxorubicin (Doxo) and UV irradiation for 12 h, and then BAX in cytosol (Cyt) and mitochondria (Mit) was assayed by western blotting (A-C) and activation of BAX (D-F) was assayed by western blotting after IP using BAX monoclonal antibody (clone 6A7) *P0.05. AU, arbitrary units; BAX, BCL2‐associated X protein; CHAPS, 3‐[(3‐cholamidopropyl)‐dimethylammonio]‐1‐propane sulphonate buffer; Cyt c, cytochrome c; IP, immunoprecipitation; shRNA, short‐hairpin RNA; UV, ultraviolet; UVRAG, ultraviolet irradiation resistance associated gene. ",
    "ncbi_link": "UVRAG: 7405"
  },
  {
    "caption": "Time-lapse of HeLa cells expressing GFP-alpha tubulin and RFP-lifeact treated with control siRNA or siRNA against WASH1 for 48 hours arrested at prometaphase and forced to exit mitosis with Ro3306 addition (t=0). Scale bar = 5µm.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "Quantification of actin around the centrosome in (A), showing the failure to accumulate actin around the centrosome in siWASH. N = 4 experiments. Error bars represent standard deviation.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "Western blots of lysates from cells treated with siRNA control and siRNA against WASH1 probed with WASH1 antibody, showing the reduction in WASH levels following treatment of cells with siRNA against WASH. Scale bar = 5µm and 2µm in zoom.",
    "ncbi_link": "WASH: 100287171
WASH1: 100287171"
  },
  {
    "caption": "Z-projection of HeLa cells expressing GFP-centrin1 treated with control siRNA or siRNA against WASH, arrested at prometaphase or forced to exit mitosis and immunostained with phalloidin. Scale bar-5µm Quantification of actin around the centrosome in (F), showing the failure to accumulated actin around the centrosome during forced exit in cells treated with siRNA against WASH. siControl-STLC= 1 ± 0.0189, n=165, siWASH-STLC=0.9138 ± 0.0298, n=118, siControl-STLC+RO-3306=1.911 ± 0.06221, n=147, siWASH-STLC+RO-3306=1.103 ± 0.0301, n=140. Error bars represent standard deviation. P<0.0001, one-way ANOVA.",
    "ncbi_link": "WASH: 100287171"
  },
  {
    "caption": "G Representative lung sections from WT or IFITM3 KO animals stained for SARS-CoV-2 N protein. Scale bars represent 2 mm for whole lung images. Colored boxes overlaying the whole lung images correspond to the displayed magnified regions and scale bars in these images represent 0.2 mm. Red triangles, infected airways; solid black arrow, non-infected blood vessels; open black arrow, infected blood vessels.",
    "ncbi_link": "IFITM3: 66141"
  },
  {
    "caption": "K18-hACE2 (hACE2) and K18-hACE2/IFITM3 KO mice were infected with 104 TCID SARS-CoV-2 WA1. A Weight loss (data points represent mean and error bars represent SEM, data from two independent experiments [hACE2 n=7, hACE2/IFITM3 KO n=8], skull/crossbones indicates that KO mice did not survive beyond this timepoint, *p < 0.05, ** p < 0.01, ANOVA with Bonferoni's multiple comparison's test).",
    "ncbi_link": "ACE2: 59272
IFITM3: 66141"
  },
  {
    "caption": "K18-hACE2 (hACE2) and K18-hACE2/IFITM3 KO mice were infected with 104 TCID SARS-CoV-2 WA1. C Viral titers in extrapulmonary organs on the indicated days post infection were measured (bars/error bars represent mean ± SD, data points represent distinct biological samples, day 3 data for heart, spleen, and brain are from two independent experiments, day 3 data for liver and kidney and day 5 data are from single experiments, data points at the x axis represent samples below the limit of detection, **p < 0.01, Mann-Whitney test).",
    "ncbi_link": "ACE2: 59272
IFITM3: 66141"
  },
  {
    "caption": "K18-hACE2 (hACE2) and K18-hACE2/IFITM3 KO mice were infected with 104 TCID SARS-CoV-2 WA1. D Representative lung sections from WT mice infected with SARS-CoV-2 MA10 (105 TCID) or K18-hACE2 or K18-hACE2/IFITM3 KO mice infected with SARS-CoV-2 WA1 (104 TCID) stained for SARS-CoV-2 N protein at day 5 post infection. Scale bars represent 2mm.",
    "ncbi_link": "ACE2: 59272
IFITM3: 66141"
  },
  {
    "caption": "WT and IFITM3 KO mice were intranasally infected with 105 TCID50 SARS-CoV-2 MA10 or mock infected with PBS (Non-Infected, NI). A Representative lung images from mice at the indicated times post infection were stained with hematoxylin and eosin. Scale bars represent 2mm for whole lung images and 500um for zoomed images. B Staining quantifications from multiple mice are shown (bars/error bars represent mean ± SD, data points represent distinct biological samples, *p < 0.05, ANOVA with Bonferoni's multiple comparison's test).",
    "ncbi_link": "IFITM3: 66141"
  },
  {
    "caption": "WT and IFITM3 KO mice were intranasally infected with 105 TCID50 SARS-CoV-2 MA10 or mock infected with PBS (Non-Infected, NI). A Representative lung images from mice at the indicated times post infection were stained with anti-CD45. Scale bars represent 2mm for whole lung images and 500um for zoomed images. B Staining quantifications from multiple mice are shown (bars/error bars represent mean ± SD, data points represent distinct biological samples, *p < 0.05, ANOVA with Bonferoni's multiple comparison's test).",
    "ncbi_link": "IFITM3: 66141"
  },
  {
    "caption": "WT and IFITM3 KO mice were intranasally infected with 105 TCID50 SARS-CoV-2 MA10. RNA sequencing analysis was performed on RNA extracted from infected WT and IFITM3 KO lungs on day 2 post infection. D Relative gene expression heat maps for genes from the top two most significant GO Biological Processes as shown in C.",
    "ncbi_link": "IFITM3: 66141"
  },
  {
    "caption": "(D) Top: Schematic of GFP expression reporter system, with the CBASS promoter, capH, and capP genes from E. coli MS115-1 and the CBASS core genes replaced with GFP. Bottom: Western blot showing GFP expression in cells with the wild-type GFP reporter or constructs lacking either capP or capH genes. RNAP: RNA polymerase loading control.",
    "ncbi_link": "capH: 
capP: 
GFP: "
  },
  {
    "caption": "(E) Western blots of the CBASS expression reporter system with FLAG-NucC showing FLAG-NucC expression after infection with phage λ cI- (multiplicity of infection: 10). MPI: minutes post infection. α-RNAP: anti-RNA polymerase loading control. Low RNAP expression at later time points is due to cell death.",
    "ncbi_link": "cI: 3827059"
  },
  {
    "caption": "(E) GFP expression reporter assay showing loss of suppression upon mutation of CapH. RNAP: RNA polymerase loading control.",
    "ncbi_link": "CapH: "
  },
  {
    "caption": "(A) Anti-GFP western blot showing coexpression in E. coli of an MBP-CapH-GFP fusion construct with wild-type or catalytic-dead (E98Q) CapP. Full-length MBP-CapH-GFP is indicated with a yellow arrowhead, and the C-terminal product of CapP cleavage is indicated with a white arrowhead. RNAP: RNA polymerase loading control.",
    "ncbi_link": "CapP: "
  },
  {
    "caption": "(F) GFP reporter assay showing effect of a CapP E98Q catalytic-dead mutant, CapH R83A mutant, or removal of CapH residues 83-107 (capH 1-82) on GFP expression. RNAP: RNA polymerase loading control.",
    "ncbi_link": "CapH: 
CapP: "
  },
  {
    "caption": "(G) CBASS expression reporter system with FLAG-NucC, showing effect of a CapH R83A mutant, or removal of CapH residues 83-107 (capH 1-82) on FLAG-NucC expression. α-RNAP: anti-RNA polymerase loading control.",
    "ncbi_link": "capH: 
CapH: "
  },
  {
    "caption": " A. In vivo genetic complementation of the E. coli MC4100 wild-type (WT) and secB or/and tig knock-out derivatives by either an empty vector or one carrying the secB or tig (encoding TF) genes or derivatives (see "Plasmid" table in Appendix), as indicated. Serial dilutions of a culture (OD600= 0.5) were spotted (12μl) on LB-Ampicillin plates containing or not anhydrotetracycline (AHT; 5 ng/ml) and grown at 16°C or 30°C (as indicated). n= 3-7 biological replicates. ",
    "ncbi_link": "secB: 948123
tig: 945081"
  },
  {
    "caption": "A,B) Relative gene expression analysis of the pro- and anti-apoptotic markers Bax, Bak, Bcl-2, and Bcl-xl in Cal-78 and SW-1353 cells treated with the respective IC50 values of bortezomib for 24 h (n = 10).",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-2: 596
Bcl-xl: 598"
  },
  {
    "caption": "A,B) Relative gene expression analysis of IGF1R, Fas, and the death receptors TRAILR-1 and TRAILR-2 after bortezomib treatment with the respective IC50 concentrations for 48 h. Untreated control cells served as reference value (ratio = 1).",
    "ncbi_link": "Fas: 355
IGF1R: 3480
TRAILR-1: 8797
TRAILR-2: 8795"
  },
  {
    "caption": "A) Relative gene expression and B) western blot analysis of whole cell lysates for the expression of the autophagy markers Atg 5/12 and Beclin in Cal-78 and SW-1353 cells treated with the respective IC50 values of bortezomib for 24 h.",
    "ncbi_link": "Atg 5: 9474
Beclin: 8678"
  },
  {
    "caption": "Cell viability analysis of HeLa  cells stably expressing the sh-NC and sh-GAPDH  were treated with the indicated concentration of ADR  for 48 h. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Left, representative immunofluorescence  images of γH2AX  (C, green) in HeLa  cells transfected with scramble siRNA or si-GAPDH  after 4 Gy IR  exposure and recovered for 4 h. DNA was stained  with DAPI  (blue). Right quantification of γH2AX  foci/cell (n=50). Mann-Whitney U-test. Scale bars, 10 μm. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Left, representative immunofluorescence  images of 53BP1  (D, red) in HeLa  cells transfected with scramble siRNA or si-GAPDH  after 4 Gy IR  exposure and recovered for 4 h. DNA was stained  with DAPI  (blue). Right, quantification of 53BP1  foci/cell (n=50). Mann-Whitney U-test. Scale bars, 10 μm. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot (left) and quantification (right) of γH2AX  in HeLa  cells pre-transfected with scrambled siRNA or si-GAPDH, recovered at indicated points after 4 Gy IR  exposure. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot  (left) and quantification (right) of HR proteins in HeLa  cells transfected with scrambled siRNA and si-GAPDH. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Quantification of RAD51  (left) or γH2AX  (right) foci/cell in HeLa  cells pre-transfected with scrambled siRNA or si-GAPDH, recovered at the indicated  time points after 4 Gy IR  exposure (n=50). Mann-Whitney U-test. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot  (left) and quantification (right) of RAD51  in HeLa  cells with or without GAPDH  knockdown treated with 50 μg/mL CHX  at the indicated time points. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot  (left) and quantification (right) of RAD51  in GAPDH  knockdown HeLa  cells and control cells treated with or without MG132  (10 μM) for 10 h. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot  of cell lysates or anti-RAD51 immunoprecipitates  from HeLa  cells with scramble siRNA or si-GAPDH  transfection treated with MG132  (10 μM) for 2 h.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunoblot  (left) and quantification (right) of Flag-RAD51  in cell lysates from HEK293T  cells transfected with indicated Flag-RAD51  mutations. Endogenous RAD51  and Flag-RAD51  are denoted respectively. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "Flag: 
RAD51: 5888"
  },
  {
    "caption": "Immunoblot  of cell lysates or anti-Flag immunoprecipitates  from HEK293T  cells transfected with indicated Flag-RAD51  mutations and then exposed to 10 μM MG132. Immunoblot  of cell lysates or anti-Flag immunoprecipitates  from HEK293T  cells transfected with HA-Ubiquitin   and indicated Flag-RAD51  mutations and then exposed to 10 μM MG132.",
    "ncbi_link": "Flag: 
HA: 
RAD51: 5888"
  },
  {
    "caption": "Immunoblot  (upper) and quantification (lower) of RAD51  in HEK293T  cells transfected with empty vector, Flag-HDAC1, Flag-HDAC1-S3 (∆306-353), and Flag-HDAC1-H141A. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "Flag: 
HDAC1: 3065"
  },
  {
    "caption": "HeLa  cells were transfected with empty vector, Flag-HDAC1, and Flag-HDAC1-H141A, then subjected to immunoprecipitation  and immunoblots as indicated.",
    "ncbi_link": "Flag: 
HDAC1: 3065"
  },
  {
    "caption": "Left, GAPDH  knockdown HeLa  cells transfected with Flag-HDAC1  were treated with 4 Gy IR, fixed after 4 h, and immunostained  with anti-RAD51  (red). DNA was stained  with DAPI  (blue). The number of RAD51  foci per cell is shown (right, n=50). Mann-Whitney U-test. Scale bars, 5 μm. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "Flag: 
GAPDH: 2597
HDAC1: 3065"
  },
  {
    "caption": "Immunoblot  (upper) and quantification (lower) of γH2AX  in GAPDH  knockdown HeLa  cells transfected with or without Flag-HDAC1  at the different time points after 4 Gy IR  exposure. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "Flag: 
GAPDH: 2597
HDAC1: 3065"
  },
  {
    "caption": "Left, GAPDH  knockdown HeLa  cells transfected with Flag-HDAC1  were treated with 4 Gy IR, fixed after 4 h, and immunostained  with anti- γH2AX  (green). DNA was stained  with DAPI  (blue). The number of γH2AX  foci per cell is shown (right, n=50). Mann-Whitney U-test. Scale bars, 5 μm. Data information: Data represented as mean ± s.d. of at least three independent experiments. P values are from Student's t-tests. *P<0.05; **P<0.01; ***P<0.001; ns: not significant",
    "ncbi_link": "Flag: 
GAPDH: 2597
HDAC1: 3065"
  },
  {
    "caption": "B. Dot blot of tau levels in media from HEK293T cells overexpressing tau and FLAG-DnaJC5 compared to empty vector and tau. Intracellular protein levels are shown by Western blot, DnaJC5 was detected by FLAG antibody. Quantification of extracellular tau levels shown below; data are mean ± SEM, n=8, ***p<0.001.",
    "ncbi_link": "DnaJC5: 79130
tau: 4137"
  },
  {
    "caption": "C. Light/heavy ratio of tau peptides in label-free mass spectroscopy of media from HEK293T cells overexpressing tau or tau and DnaJC5 compared to 100 ng 15N labelled recombinant tau. Light peptides represent endogenous tau peptides. Data are mean ± SEM, n=3 biological repeats, ***p<0.001.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "A. Western blot of endogenous tau levels from M17 neuroblastoma cells overexpressing FLAG-DnaJC5 or empty vector. Media was concentrated prior to analysis. Intracellular DnaJC5 was detected with FLAG antibody. Quantification of extracellular tau levels are mean ± SEM, n=3, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "B. Western blottau levels from concentrated media from ex-vivo organotypic slice cultures of wildtype mice overexpressing GFP-AAV9 or FLAG-DnaJC5-AAV9. DnaJC5 is detected by FLAG antibody. Quantification of extracellular tau levels are mean ± SEM, n=3, **p<0.01 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "C. Western blottau levels from concentrated media from ex-vivo organotypic slice cultures of Cspa+/+ or Cspa-/- mice. DnaJC5 was detected by DnaJC5 antibody (Synaptic Systems). Quantification of extracellular tau levels are mean ± SEM, n=3, **p<0.01 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "Cspa: 13002"
  },
  {
    "caption": "A. FLAG-DnaJC5 overexpression facilitates extracellular release of wildtype (WT), P301L and R406W tau by dot blot in HEK293T cells. Intracellular protein levels are shown by Western blot; DnaJC5 was detected by FLAG antibody. Quantification of extracellular tau levels shown below; data are mean ± SEM, n=3, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130
tau: 4137"
  },
  {
    "caption": "B. Overexpression of FLAG-DnaJC5 induces extracellular release of wildtype (WT) and A53T α-synuclein in HEK293T cells. Extracellular protein levels shown by dot blot (quantification below, mean ±SEM, n=3 ***p<0.001, ** p<0.01 by one-way analysis of variance with Tukey's multiple comparison post-hoc analysis) and intracellular proteins levels were analyzed by Western blot, DnaJC5 was detected by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130
α-synuclein: 6622"
  },
  {
    "caption": "C. DnaJC5 overexpression induces extracellular release of GFP-tagged wildtype (WT), A315T and Q343R TDP-43 in HEK293T cells. Intracellular DnaJC5 was detected by FLAG antibody. Extracellular protein levels are analyzed by dot blot (quantification below, mean ±SEM, n=4) ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130
TDP-43: 23435"
  },
  {
    "caption": "A. Dot blot of tau levels in media of cells overexpressing the phospho-deficient FLAG-DnaJC5 S10A compared to FLAG-DnaJC5 WT. Intracellular levels shown by Western blot, DnaJC5 was detected by FLAG antibody. Quantification of tau levels are mean ± SEM, n=6, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "B. Knockdown of SNAP23 by siRNA inhibits DnaJC5-mediated tau release in HEK293T cells as shown by dot blot. Quantification of extracellular levels are mean ± SEM, n=3, **p<0.01 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis. DnaJC5 was detected by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130
SNAP23: 8773"
  },
  {
    "caption": "C. Knockdown of SNAP23 by siRNA inhibits DnaJC5-mediated α-synuclein release in M17 cells as shown by dot blot. Quantification of extracellular levels are mean ± SEM, n=3, **p<0.01 by one-way ANOVA with a Tukey's post-hoc analysis. DnaJC5 is detected by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130
SNAP23: 8773"
  },
  {
    "caption": "D. Knockdown of SNAP23 by siRNA inhibits DnaJC5-mediated TDP-43 release in M17 cells as shown by dot blot. Quantification of extracellular levels are mean ± SEM, n=3, **p<0.01 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis. DnaJC5 was detected by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130
SNAP23: 8773"
  },
  {
    "caption": "A. Confocal microscopy of tau (red pseudocolor) and Hsp70 (green pseudocolor) colocalization (merged image) levels in wild type primary neurons overexpressing GFP-AAV9 or FLAG-DnaJC5-AAV9. Boxed area are 5X digital zoom on a 60X lens shown below. Scale bars are 20 µm and 5 µm as indicated. Only neurons overexpressing virus were imaged.B. Quantification of tau-Hsp70 co-localization (mean Pearson's coefficient ± SEM, n=18, *p <0.05, one-way analysis of variance with Tukey's multiple comparison post-hoc analysis).",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "D. Western blot of HEK293T intracellular lysates show the DnaJC5/Hsc70/tau complex is disrupted by the addition of increasing amounts of YM-01 (0, 10, 30, 100 µM) in a dose-dependent fashion. DnaJC5 was detected by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "E. The DnaJC5/Hsc70 complex is disrupted when Hsc70 activity is inhibited by a dominant-negative point mutation, E175S. Western blot of immunoprecipitated DnaJC5 from HEK293T cells overexpressing WT or DN E175S Hsc70. DnaJC5 is immunopreicipitated by DnaJC5 antibody (Synaptic Systems). DnaJC5 was detected on Western blot by FLAG antibody.",
    "ncbi_link": "DnaJC5: 79130
Hsc70: 3312"
  },
  {
    "caption": "G. Dot blot of tau levels in media of primary neurons from transgenic overexpressing tau P301L mice treated with YM-01 (10µM). FLAG-DnaJC5 was transduced into neurons using AAV9. Quantification of extracellular tau levels are mean ± SEM, n=6, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis. DnaJC5 was detected on Western blot by FLAG antibody.",
    "ncbi_link": "DnaJC5: 13002"
  },
  {
    "caption": "A. Chemical inhibition of Hsc70 activity in HEK293T cells overexpressing FLAG-DnaJC5 reduces extracellular tau levels as shown by dot blot. Intracellular levels are shown by Western blot, DnaJC5 was detected by FLAG antibody. Quantification of extracellular tau levels is shown as average ± SEM, n=3, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "B. Chemical inhibition of Hsc70 activity in HEK293T cells overexpressing FLAG-DnaJC5 reduces extracellular α-synuclein levels as shown by dot blot. Intracellular levels are shown by Western blotDnaJC5 was detected by FLAG antibody. Quantification of extracellular synuclein levels is shown as average ± SEM, n=3, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "C. Dominant-negative Hsc70 E175S blocks tau release when overexpressed in HEK293T cells as shown by dot blot. Intracellular levels are shown by Western blot. Quantification of extracellular tau levels is shown as average ± SEM, n=4, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "Hsc70: 3312
tau: 4137"
  },
  {
    "caption": "D. Knockdown of Hsc70 reduces extracellular tau release (dot blot) in HEK293T cells overexpressing FLAG-DnaJC5. Intracellular levels are shown by Western blot, DnaJC5 was detected by FLAG antibody. Quantification of extracellular tau levels is shown as average ± SEM, n=3, ***p<0.001 one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130"
  },
  {
    "caption": "E. A mutant tau that does not bind Hsc70 is not released when FLAG-DnaJC5 is overexpressed in HEK293T cells. Dot blot and quantification of extracellular tau levels are shown. Intracellular protein levels are shown with representative Western blot, DnaJC5 was detected by FLAG antibody. Data are mean ± SEM, n=3 p<0.001. one-way analysis of variance with Tukey's multiple comparison post-hoc analysis.",
    "ncbi_link": "DnaJC5: 79130
tau: 4137"
  },
  {
    "caption": "H. Dot blot of increasing FLAG-DnaJC7 levels on FLAG-DnaJC5 overexpression-mediated extracellular tau release in HEK293T cells. Intracellular protein levels are shown with representative Western blot, DnaJ proteins were detected by FLAG antibody. Quantification of extracellular levels are mean ± SEM, n=4.",
    "ncbi_link": "DnaJC5: 79130
DnaJC7: 7266"
  },
  {
    "caption": "(B, Performance in the multi-trail inverted screen test  is impaired in (B) SUR2-STOP1149 (WT n = 9 [3 male; 6 female]; STOP n = 9 [3 male; 6 female]; p = 0.011 according to Mann Whitney U test) Data information: Bars show mean (± SEM) with individual biological replicates shown as circles/squares. * denotes p value < α = 0.05 for all panels.",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "C) Performance in the multi-trail inverted screen test  is impaired in (C) SUR2-STOP475 mice  (WT n = 9 [4 male; 5 female]; STOP n = 15 [5 male; 10 female]; p = 2.9x10-4 according to Mann Whitney U test). Data information: Bars show mean (± SEM) with individual biological replicates shown as circles/squares. * denotes p value < α = 0.05 for all panels.",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(D)Treadmill exercise tolerance is also reduced in SUR2-STOP475 mice  (WT n = 4 [2 male; 2 female]; STOP n = 8 [4 male; 4 female]; p = 0.008 according to Mann Whitney U test). Treadmill workload tolerated was also reduced (WT 18.1 ± 2.2 vs STOP475 9.2 ± 0.9 J; p = 0.008 from Man Whitney U test), mean mouse  body weight  was WT 22.1 ± 0.9 vs STOP475 21.9 ± 0.6 g. Data information: Bars show mean (± SEM) with individual biological replicates shown as circles/squares. * denotes p value < α = 0.05 for all panels.",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(A) Example traces of inside-out patch clamp  recordings of acutely isolated FDB myofibers  of WT (black, top left), SUR2-STOP475 (purple, top right), and skeletal muscle dominant negative (SkM-DN; magenta, bottom left) mice. Patches were voltage clamped at -50 mV and excised at time-points indicated by arrows. ATP  (5 mM) was administered to the cytoplasmic  face of membrane patches as indicated by horizontal bars. Dashed lines denote the zero KATP   current level.",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(D) Distance travelled in  treadmill exercise tolerance tests (all male; WT n = 6; AAA+ n = 8; Myf5-cre  n = 8; SkM-DN n = 7; Dunn's test following Kruskal-Wallis omnibus test p = 0.005 for WT vs SkM-DN, 0.037 for AAA+ vs SkM-DN, and 0.014 for Myf5-cre  vs SkM-DN; * denotes p value < adjusted α = 0.0083). Treadmill workload tolerated was also reduced (WT 23.6 ± 2.3 vs SkMDN 10.1 ± 1.8 J; p = 0.0017 from Dunn's test), mean mouse  body weight  was WT 28.9 ± 1.6, AAA+ 26.6 ± 0.9, Myf5-cre  25.3 ± 0.8, SkMDN 24.2 ± 0.8 g; no significant differences in body weights  were observed, p from Dunn's test following Kruskal-Wallis omnibus test > adjusted α = 0.0083 for all comparisons. Bars show mean (± SEM) with individual mouse performance shown as dots/diamonds/triangles/squares.",
    "ncbi_link": "cre: 2777477
Myf5: 17877"
  },
  {
    "caption": "(A) Left - example HE stained tibialis anterior (TA) muscles from WT and SUR2-STOP475 mice. Black arrows identify peripheral nuclei  and yellow arrows indicate centrally nucleated fibers. Right - quantification of centrally nucleated fibers. Bars show mean (± SEM) with individual biological replicates shown as dots/squares (WT n = 5; STOP n = 4; p = 0.016 according to Mann Whitney U test) (B) Left - example HE stained TA  muscles from control and SkM-DN mice. Black arrows identify peripheral nuclei  and yellow arrows indicate centrally nucleated fibers. Right - quantification of centrally nucleated fibers. Bars show mean (± SEM) with individual biological replicates shown as dots/squares (Control n = 7 [comprising 2 x WT, 3 x Myf5+-cre, and 2 x AAA+ littermate controls]; SkM-DN n = 5; p = 0.002 according to Mann Whitney U test). Data information: * denotes p value < α = 0.05 for all panels. Scale bars show 50 µm in each panel.",
    "ncbi_link": "SUR2: 20928
cre: 2777477
Myf5: 17877"
  },
  {
    "caption": "(A) Example traces showing force  generation in  isometric contractility studies  of isolated EDL  muscle from WT (left, black) and SUR2-STOP475 (right, purple) mice. Muscle was stimulated every 2 s. Scale bars show 20 mN (y-axis) and 2 s (x-axis). (B) Enlarged representations of the 1st (at 0 seconds), 10th (20 s) and 30th (60 s) contractions, identified in concatenated traces in (A) by arrows. Scale bars show 20 mN (y-axis) and 0.4 s (x-axis).",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(A) Survival  of WT and SUR2-STOP475 mice  administered with verapamil  in drinking water (n = 7 [4 male, 3 female] for WT administered 0.9 g/l verapamil; n = 14 [8 male, 6 female] for SUR2-STOP475 administered 0.9 g/l verapamil; n = 6 [3 male, 3 female] for SUR2-STOP475 administered 0.3 g/l verapamil). Verapamil  induced deaths were observed in both male  and female mice  (7 of 8 male  and 4 of 6 female SUR2-STOP475 mice  died within 28 days of 0.9 g/l verapamil). (B) Survival  of WT and SUR2-STOP1149 mice  administered with verapamil  in drinking water (n = 10 [3 male, 7 female] for SUR2-STOP1149 mice  administered 0.9 g/l verapamil).",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(D) Heart  rates calculated from ECG  recordings from WT and SUR2-STOP mice  administered with no verapamil  (0 Verap) or 0.9 g/l verapamil  in drinking water.",
    "ncbi_link": "SUR2: 20928"
  },
  {
    "caption": "(A) Left - Average performance in the  inverted screen test  of mice  homozygous for the ncDHPR   allele alone (ncDHPR) or homozygous for both the ncDHPR and SUR2-STOP475 alleles (STOP475/ncDHPR). Right - Summary of inverted screen test data. Data shown as mean ± SEM (WT n = 9 [4 male; 5 female]; ncDHPR n = 15 [male  6; female  9]; STOP475 n = 15 [5 male; 10 female]; STOP475/ncDHPR n = 12 [4 male; 12 female]; Dunn's test p = 4.0 x 10-4 for WT vs STOP475, 6.9 x 10-4 for WT vs STOP475/ncDHPR, 0.001 for ncDHPR  vs STOP475/ncDHPR verapamil, following Kruskal-Wallis omnibus test). * denotes p value < adjusted α = 0.0083.",
    "ncbi_link": "SUR2: 20928
DHPR: 12292"
  },
  {
    "caption": "(B) Left - Example of HE stained tibialis anterior muscle from STOP475/ncDHPR mouse, black arrow shows  peripheral nuclei   and yellow arrows show central nuclei. Right - Quantification of centrally nucleated fibers, data from WT and SUR2-STOP475 mice  (WT n = 5; STOP475 n = 4; STOP475/ncDHPR n = 8; Dunn's test p = 0.007 for WT vs STOP475 and 0.011 for WT vs STOP475/ncDHPR, following Kruskal-Wallis test, * denotes p value < adjusted α = 0.067). Scale bar shows 50 µm. Bars show mean (± SEM) with individual measurements shown as dots/squares/triangles.",
    "ncbi_link": "SUR2: 20928
DHPR: 12292"
  },
  {
    "caption": "(F) Summary of unstimulated force  (normalised by physiological cross-sectional area) at 60 s for each experiment. Bars show mean ± SEM with individual biological replicates shown as dots/squares/triangles (WT without glibenclamide  n = 6 [3 male; 3 female]; WT with glibenclamide  n = 10 [5 male; 5 female]; ncDHPR  without glibenclamide  n = 6 [3 male; 3 female]; ncDHPR with glibenclamide  n = 6 [3 male; 3 female]; Dunn's test p = 7.0 x 10-4 for WT without glibenclamide  vs WT with glibenclamide  and 0.002 for ncDHPR without glibenclamide  vs ncDHPR with glibenclamide, following Kruskal-Wallis omnibus test; * denotes p value < adjusted α = 0.0083).",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "D The expression of FUNDC1 is induced by 10 ng/ml tetracycline (Tet) in FUNDC1‐inducible HeLa cells. Cells were transfected with HA‐ULK1 or HA‐ULK1 (K46N) for 24 h. Then, the cell lysates were prepared for immunoblotting using indicated antibodies.",
    "ncbi_link": "FUNDC1: 139341
ULK1: 8408"
  },
  {
    "caption": "EULK1+/+ cells were transfected with FUNDC1‐Myc, and ULK1-/- cells were transfected with FUNDC1‐Myc alone, FUNDC1‐Myc and HA‐ULK1, or FUNDC1‐Myc and HA‐ULK1 (K46N). Cells were harvested and lysed for immunoblots24 h after transfection.",
    "ncbi_link": "FUNDC1: 139341
ULK1: 8408"
  },
  {
    "caption": "F Purified GST‐FUNDC1 and GST‐FUNDC1 (S17A) were subjected to an in vitro kinase assay with Myc‐ULK1 immunoprecipitated by anti‐Myc antibody from Myc‐ULK1‐transfected cells about 24 h post‐transfection. Phosphorylated FUNDC1 was detected by anti‐p‐S17‐FUNDC1 antibody. The red asterisks mark the target bands.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "I, J The single mutant which can abolish the ULK1 and FUNDC1 interaction was identified. HeLa cells were co‐transfected with Flag‐ULK1 and the indicated constructs. 24 h after transfection, cells were lysed for immunoprecipitation by anti‐Flag antibody.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "KMEFs were transfected with FUNDC1‐Myc and its mutants after the endogenous FUNDC1 was knocked down by siRNA. 36 h after transfection, cells were harvested in the absence or presence of 50 nM bafilomycin A1 (BAF1) and then lysed for immunoblotting with the indicated antibodies.",
    "ncbi_link": "FUNDC1: 72018"
  },
  {
    "caption": "L MEFs were co‐transfected with FUNDC1‐Myc or its mutants and MitoDsred after the endogenous FUNDC1 was knocked down by siRNA. 24 h post‐transfection, cells were treated with hypoxic (1% O2) conditions for 12 h or FCCP (20 μM) for 6 h before fixed by 4% paraformaldehyde and stained with indicated antibodies. Scale bar, 10 μm.",
    "ncbi_link": "FUNDC1: 72018"
  },
  {
    "caption": "AULK1+/+ and ULK1−/− cells were cultured under hypoxic (1% O2) condition for 12 h or 24 h in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cell lysates were immunoblotted.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "B ULK1+/+ and ULK1−/− cells were treated with FCCP (20 μM) for the indicated times in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cell lysates were immunoblotted.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "C ULK1+/+ and ULK1−/− cells were transfected with FUNDC1−Myc for 24 h and then harvested in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cell lysates were immunoblotted.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "D ULK1−/− cells were transfected with HA‐ULK1 or HA‐ULK1 (K46N), then cultured under hypoxic (1% O2) conditions for 24 h in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cells lysates were immunoblotted.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "EULK1−/− cells were transfected with HA−ULK1 or HA−ULK1 and then treated with FCCP (20 μM) for 24 h. Cells were harvested in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cell lysates were immunoblotted.",
    "ncbi_link": "ULK1: 22241"
  },
  {
    "caption": "F FUNDC1‐knockdown MEFs were transfected with FUNDC1‐Myc or FUNDC1-Myc (S17A) for the indicated times. Cell lysates were used for immunoblotting.",
    "ncbi_link": "FUNDC1: 72018"
  },
  {
    "caption": "G ULK1+/+ cells were transfected with FUNDC1‐Myc, and ULK1−/− cells were transfected with FUNDC1‐Myc or FUNDC1-Myc (S17D). 24 h after transfection, cells were fixed with 4% paraformaldehyde and stained with anti‐Myc (mouse) and anti‐LC3 (rabbit) primary antibodies for immunofluorescence microscopy. Scale bar, 10 μm.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "H ULK1−/− cells were transfected with FUNDC1‐Myc or FUNDC1-Myc (S17D) for 24 h in the absence or presence of 50 nm bafilomycin A1 (BAF1) for an additional 6 h before harvesting. Cell lysates were immunoblotted.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "I ULK1−/− cells were transfected with FUNDC1‐Myc or FUNDC1-Myc (S17D) for 24 h in the absence or presence of 50 nm bafilomycin A1 (BAF1) for an additional 6 h before harvesting. Cell lysates were detected with the citrate synthase activity kit.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "J HeLa cells were transfected with FUNDC1‐Myc, FUNDC1-Myc (S17A), or FUNDC1-Myc (S17D). 24 h after transfection, cell lysates were immunoprecipitated with anti‐LC3 antibody.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "A ULK1+/+ or ULK1−/− cells were cultured under hypoxic (1% O2) or normoxic conditions in the absence or presence of 50 nM bafilomycin A1 (BAF1). ULK1−/− cells were transfected with HA‐ULK1, and ULK1−/− FUNDC1‐KD cells were transfected with HA‐ULK1 and FUNDC1‐Myc, then cultured under hypoxic (1% O2) conditions for 24 h in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cells were harvested and lysed for immunoblotting assays.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "B ULK1+/+ or ULK1−/− cells were treated with or without FCCP (20 μM) in the absence or presence of 50 nM bafilomycin A1 (BAF1). ULK1−/− cells were transfected with HA‐ULK1 and ULK1−/− FUNDC1‐KD cells were transfected with HA‐ULK1 and FUNDC1‐Myc and then treated with FCCP (20 μM) for 24 h in the absence or presence of 50 nM bafilomycin A1 (BAF1). Cells were harvested and lysed for immunoblotting assays.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "C ULK1+/+, ULK1−/− FUNDC1‐KD, or ULK1−/− FUNDC1‐KD cells rescued by introduction of HA‐ULK1 and FUNDC1‐Myc were cultured under hypoxic (1% O2) conditions for 24 h or with FCCP (20 μM) for 24 h. Samples were analyzed by electron microscopy. Scale bar, 2 μm. The yellow asterisks mark mitochondria. The red arrows indicate double‐membraned autophagic structures. The yellow arrow denotes autolysosomes.",
    "ncbi_link": "FUNDC1: 72018
ULK1: 22241"
  },
  {
    "caption": "Immunoblot analyses of TDG and TDG-SUMO in whole cell extracts of mESCs and MEFs. TDG and TDG-SUMO conjugates before (2i, 0 h) and during differentiation of TDG wildtype (TDGwt) and TDG deficient (TDGnull) mESC and MEFs (5 µM all-trans retinoic acid (RA, 24 h, 48 h). Percentages of TDG-SUMO relative to total TDG signal are indicated.",
    "ncbi_link": "TDG: 21665"
  },
  {
    "caption": "Immunoblot analyses of TDG and TDG-SUMO in whole cell extracts of mESCs Chromatin fractionation from mESCs expressing wildtype (ESC-TDGwt) or SUMOylation-deficient TDG (ESC-TDGsnm). Sol, chromatin unbound proteins; Chr1, chromatin associated proteins; Chr2, chromatin bound fraction; Histone H2B, stably chromatin bound marker.",
    "ncbi_link": "TDG: 21665"
  },
  {
    "caption": "Fluorescence microscopy of GFP-TDGwt GFP-TDGpip in mESCs. Scale bar: 100µM. Quantitation of fluorescence signals of GFP-TDGwt and GFP-TDGpip in mESCs. median with interquartile range. >470 cells were analysed of each GFPTDGwt and GFPTDGpip ESCs.",
    "ncbi_link": "TDG: 21665"
  },
  {
    "caption": "Immunoblot analysis of XRCC1 and XRCC1-SUMO in GFP-TDGwt and GFP-TDGpip mESCs.",
    "ncbi_link": "GFP: 
TDG: 21665"
  },
  {
    "caption": "Immunoblot analysis of XRCC1, TDG, TDG-SUMO in TDGwt (wt), TDGsnm (snm) and XRCC1null mESCs (null).",
    "ncbi_link": "TDG: 21665
XRCC1: 22594"
  },
  {
    "caption": "Immunoblot analysis of TDG and TDG-SUMO in TDGwt (wt) and XRCC1null mESCs (null) exposed to H2O2 as indicated.",
    "ncbi_link": "TDG: 21665
XRCC1: 22594"
  },
  {
    "caption": "Bright field captures of TDGwt, TDGcat and TDGsnm mESCs at indicated stages of differentiation. DAPI, Alexa Fluor® 680 phalloidin actin staining at the bottom. Scale bars 25µM, 50µM, 500µM as indicated. Quantification of neural cells with neurites of total differentiating TDGwt, TDGcat and TDGsnm mESCs. n ≥ 5. Means with standard deviation (SD). **: P<0.01. Non parametric, Mann-Whitney test.",
    "ncbi_link": "TDG: 21665"
  },
  {
    "caption": "Relative changes of lineage marker expression between NPCs and undifferentiated mESCs (ESCM LIF, 0 h), quantified with Gapdh as normalizer. n ≥ 3. Means with standard deviation (SD)). *: P<0.05; **: P<0.01 by non parametric Mann-Whitney test.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "Representative images of mESC neuronal differentiation as in Fig 4B. Shown are XRCC1wt and XRCC1null (XRCC1null1, XRCC1null2) mESCs in 2i medium supplemented with LIF (2i LIF) and in ESC medium supplemented with LIF (ESCM LIF), EBs in ESCM LIF and 5µM RA (EB 4d ESCM RA) and dissociated neuron-like cells in B27 (B27). Scale bars 25µM, 50µM, 500µM as indicated. Neurite grids were observed for XRCC1wt; heterogeneous cell populations formed with the XRCC1null (XRCC1null1, null2) clones. Quantification (below) of neural cells with neurites of total differentiating XRCC1wt, XRCC1null mESCs. n = 5. Means with standard deviation (SD). **: P<0.01. Non parametric, Mann-Whitney test.",
    "ncbi_link": "XRCC1: 22594"
  },
  {
    "caption": "Quantification of mRNA expression of pluripotency and ectodermal/neurogenesis marker genes by RT-qPCR. n ≥ 3. Mean values and standard deviations (SD) of EBs relative to their mESC (ESCM LIF, 16h), normalised to Gapdh.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "Dox-induced prolongation of Nanog expression in Nanogtg embryos up to E9.5 results in lack of blood (left) and downregulation of erythropoietic gene expression. The center and right panels show whole-mount in situ hybridization for Hbb-bh1 (in embryos with intact yolk sacs) and for the long non-coding RNA Redrum. Asterisks mark the aorta-gonad-mesonephros region (AGM) and arrows the tailbud. Embryos of the same genotype but not treated with dox were used as controls (-dox). Scale bars, 500 µm.",
    "ncbi_link": "Hbb-bh1: 15132
Nanog: 71950
Redrum: 77433"
  },
  {
    "caption": "Endomucin staining of vessels in control (-dox) or treated (+dox) E9.5 Nanogtg embryos. On the right, higher magnifications of the boxed areas. Scale bar, 500 µm.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Representative FACS plot of the distribution of the CD71 and Ter119 populations in dissected yolk sacs from untreated and dox-treated E9.5 Nanogtg embryos. Quantification of the CD71+ Ter119+ population in controls (-dox, black dots; n=8) and Nanog expressing (+dox, red dots; n=7) E9.5 yolk sacs. Each replicate contained a pool of 5 (-dox) or 8 (+dox) E9.5 Nanogtg embryos. ***P. < 0.0005; Student's t-test. Horizontal line represents mean values and error bars standard deviation (SD).",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Representative FACS plots showing the distribution of cKit and CD41 populations in yolk sacs from untreated controls (-dox) and Nanog expressing (+dox) E9.5 Nanogtg embryos. Quantification of different progenitor populations in yolk sacs from control (-dox, black dots; n=8) and Nanog expressing (+dox, red dots; n=7) E9.5 embryos. Each replicate contained a pool of 5 (-dox) or 8 (+dox) E9.5 Nanogtg embryos. Horizontal line represents mean values and error bars SD.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Differences in the expression levels of Nanog and selected hematopoietic genes in the CD71+ Ter119+ population of control (-dox; n=7) and Nanog-expressing (+dox; n=4) E9.5 embryos. **P < 0.005, ***P < 0.0005; Student's t-test. Horizontal line represents mean values and error bars SD.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Freshly dissected dox-treated Nanogtg E10.5 embryos without (control) and with (chimera) contribution of wt-ESGFP cells (left, brightfield; right, GFP). Arrows mark the presence of blood in chimeric embryos that is absent from controls. Scale bar, 500 µm.",
    "ncbi_link": "GFP: 
Nanog: 71950"
  },
  {
    "caption": "Quantification of colony-forming units generated by wild type (wt) and knockout (Nanog-/-) ES cells after culture of EBs for 5 (D5), 6 (D6), or 7 (D7) days and plating disaggregated cells in different hemogenic-promoting conditions). Panels on the left show representative images of mouse hematopoietic colonies obtained after 12 days of culture in specific media. CFU-GEMM, progenitors giving rise to granulocytes, erythrocytes, monocytes, and megakaryocytes; BFU-E, burst forming units-erythroid; Ery-P, colony forming primitive erythroid; CFU-GM, granulocyte-monocyte precursors; CFU-M, monocyte precursors; CFU-G, granulocyte precursors. No CFU-GEMM are detected at D5 and no BFU-E at D7. For both wt and knockout cells, n=3 each with 3 technical replicates. *P < 0.05, **P < 0.005, ***P < 0.00005; Student's t-test. Horizontal line represents mean values and error bars SD.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "RT-qPCR determination of the relative expression of Brachyury and selected hematopoietic genes in control (wt, right) and knockout (Nanog-/-, left) ES cells (n=3) during 10 days of EB differentiation in hematopoietic-cytokine-enriched medium. Black arrowheads indicate the peak of Brachyury expression and white arrowheads the time of maximum hematopoietic-gene expression.",
    "ncbi_link": "Nanog: 71950
Brachyury: 20997"
  },
  {
    "caption": "Representative FACS plots showing the distribution of CD16/32 and CD34 hematopoietic precursors sorted from the cKit+Sca1-LIN- bone marrow of untreated (-dox) or treated (+dox) adult Nanogtg mice.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Contribution of Nanogtg transplanted bone marrow cells to peripheral blood before (left) and after (right) dox treatment. Percentage of host derived cells (CD45.1+) are shown in black, and of donor derived cells (CD45.1/CD45.2 double +) in red. Individual mice are indicated on the x-axis (n=7).",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Contribution of Nanogtg transplanted cells to LSK, CMP, GMP and MEP populations purified from bone marrow. Percentage of host derived cells (CD45.1+) are show in black, and of donor derived cells (CD45.1/CD45.2 double +) in blue. Individual mice are indicated on the x-axis (n=7).",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Expected and observed number of mesodermal (Flk1+) cells of the E7.0 mouse embryo expressing Nanog and selected mesodermal or hematopoietic gene expression, based on single cell RNA-seq data (Scialdone et al., 2016). Statistical significance was calculated with a hypergeometric test.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "PCA showing the distribution of Flk1+ E7.0 mesoderm cells expressing Nanog (green) or Tal1 (red). The single cell expressing both genes is shown in yellow and indicated by an arrow.",
    "ncbi_link": "Nanog: 71950
Tal1: 21349"
  },
  {
    "caption": "E6.5 Nanogtg embryos after 8 hours ex-utero culture in the presence (+dox) or absence (-dox) of doxycycline. Scale bar, 100 µm.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "RT-qPCR quantification of the relative expression of Nanog, Tal1, and Klf1 in individual untreated embryos (-dox) or treated embryos (+dox) (n=5). **P < 0.005, ***P < 0.0005; Student's t-test. Horizontal line represents mean values and error bars SD.",
    "ncbi_link": "Klf1: 16596
Nanog: 71950
Tal1: 21349"
  },
  {
    "caption": "Whole mount in situ hybridization of Tal1 in E7.5 untreated (-dox) or in utero treated (+dox) Nanogtg embryos. Scale bar, 100 µm.",
    "ncbi_link": "Nanog: 71950
Tal1: 21349"
  },
  {
    "caption": "RT-qPCR determination of relative expression in wild type and CRISPR-deleted embryos (n=5) of Tal1 (wt, n=19; deleted, n=13), Klf1 (wt, n=3; deleted, n=6), Gfi1b (wt, n=10; deleted, n=8), Runx1 (wt, n=13; deleted, n=5) and Stil (wt, n=19; deleted, n=13). **P < 0.005, Student's t-test. Horizontal line represents mean values and error bars SD.",
    "ncbi_link": "CRISPR: 
Gfi1b: 14582
Klf1: 16596
Runx1: 12394
Stil: 20460
Tal1: 21349"
  },
  {
    "caption": "Experimental design for ES to EpiL cell differentiation of Nanogtg cells and two independent clones (Nanogtg;dTal1del#1 and Nanogtg;dTal1del#2) where the binding site for NANOG distal to Tal1 has been deleted (left). On the right, relative expression of Tal1 determined by RT-qPCR for each ES cell line (ESC; n=9 for all three lines) and EpiL cells without (EpiLC; Nanogtg and Nanogtg;dTal1del#1, n=8; Nanogtg;dTal1del#2, n=6) or with dox treatment (EpiLC +dox; n=9 for all three lines). The genotype of the cell lines is indicated below. Values were normalized to Nanogtg ESC. *P < 0.05, **P < 0.01, ns = not significant; ANOVA with Fisher post-test. Horizontal line represents mean values and error bars standard error of the mean (SEM).  ",
    "ncbi_link": "Nanog: 71950
Tal1: 21349"
  },
  {
    "caption": "WB analysis of OTUB1 expression in cultured primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Direct ex vivo WB analysis of OTUB1 expression in astrocytes isolated from adult OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Normal CNS architecture in OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice. Myelination is normal in the brain and spinal cord of an OTUB1fl/fl and a GFAP-Cre OTUB1fl/fl mouse. CV-LFB staining; original magnification ×50; scale bars correspond to 100 µm. All photographs are representative of three mice per group.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Absolute numbers of CD45+ cells in the spinal cord of OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice (n = 5 for both groups, mean + SEM). Absolute numbers of different subpopulations of leukocytes infiltrating the spinal cord of OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were analyzed by flow cytometry (n = 5 for both groups, mean + SEM).",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "In an OTUB1fl/fl and a GFAP-Cre OTUB1fl/fl mouse, OTUB1 is strongly expressed by NeuN+ neurons in the brain and spinal cord. Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-NeuN (FITC). Single NogoA+ oligodendrocytes in the brain and spinal cord (arrows) of an OTUB1fl/fl and a GFAP-Cre OTUB1fl/fl mouse express OTUB1. Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-NogoA (Alexa Fluor 488). GFAP+ astrocytes are of normal morphology and distribution in the brain and spinal cord of a non-immunized OTUB1fl/fl mouse and a GFAP-Cre OTUB1fl/fl mouse. Note that GFAP+ astrocytes of an OTUB1fl/fl mouse do not express OTUB1. GFAP+ astrocytes of a GFAP-Cre OTUB1fl/fl mouse are also OTUB1-negative and represent a negative control for OTUB1 staining. Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-GFAP (FITC).",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Activated GFAP+ astrocytes in the spinal cord upregulate OTUB1 in EAE at maximal disease activity (day 15 p.i.) in an OTUB1fl/fl mouse (arrowheads), but not in a GFAP-Cre OTUB1fl/fl mouse. Note the OTUB1-expressing neuron in an OTUB1fl/fl mouse which is surrounded by GFAP-expressing processes of an activated astrocyte (asterisk). At day 22 p.i., astrocytes have downregulated OTUB1 expression while neurons express OTUB1 in an OTUB1fl/fl mouse (asterisk). Astrocytes in a GFAP-Cre OTUB1fl/fl mouse are OTUB1-negative while neurons express OTUB1 (asterisk). At day 22 p.i., demyelination in a GFAP-Cre OTUB1fl/fl mouse is much more severe and extended as compared to an OTUB1fl/fl mouse. Inflammation persists in the GFAP-Cre OTUB1fl/fl mouse, whereas it has resolved in an OTUB1fl/fl mouse. All photographs are representative of three mice per group; original magnification ×400; scale bars correspond to 50 µm. (A, C) Double immunofluorescence with rabbit anti-OTUB1 (Cy3) and mouse anti-GFAP (FITC). (B, D) CV-LFB staining.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "EAE was induced in GFAP-Cre OTUB1fl/fl mice (n = 29) and OTUB1fl/fl control littermates (n = 29) by MOG35-55 peptide immunization with pertussis toxin. Graph represents data pooled from 4 experiments with 7-8 mice per group and shows the mean clinical scores + SEM. Statistical analysis performed using Mann-Whitney U test; * p < 0.05. EAE was induced in GFAP-Cre OTUB1fl/fl mice (n = 12) and OTUB1fl/fl control littermates (n = 12) by MOG35-55 peptide immunization without pertussis toxin. Graph represents the mean clinical scores + SEM. Statistical analysis performed using Mann-Whitney U test; * p < 0.05.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Percentages of CD4+ and CD8+ T cells infiltrating the spinal cord of OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were analyzed by flow cytometry at day 15 (n = 7 for OTUB1fl/fl group; n = 9 for GFAP-Cre OTUB1fl/fl group) and 22 (n = 4 for OTUB1fl/fl group; n = 5 for GFAP-Cre OTUB1fl/fl group) p.i. Representative dot plots are shown.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Absolute number of infiltrating leukocytes in the spinal cord of OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice at day 15 (n = 7 for OTUB1fl/fl group; n = 9 for GFAP-Cre OTUB1fl/fl group) and 22 (n = 4 for OTUB1fl/fl group; n = 5 for GFAP-Cre OTUB1fl/fl group) p.i. was calculated based on flow cytometry results. Data show mean + SEM.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Infiltrating CD4+ T cells were further analyzed by flow cytometry for their ability to produce GM-CSF, IFN-γ, and IL-17 at day 15 and 22 p.i., respectively. Representative dot plots are shown. Absolute number of infiltrating GM-CSF-, IFN-γ-, and IL-17-producing CD4+ T cells at day 15 (n = 7 for OTUB1fl/fl group; n = 9 for GFAP-Cre OTUB1fl/fl group) and 22 (n = 4 for OTUB1fl/fl group; n = 5 for GFAP-Cre OTUB1fl/fl group) p.i. was calculated based on flow cytometry results (mean + SEM).",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Relative expression of GM-CSF, IFN-γ, IL-17, TNF, IL-6, CXCL1, CXCL10, CXCL11, CCL2 and NOS2 mRNA in the spinal cord of OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice at day 15 and 22 p.i. was determined by quantitative real-time PCR. Data are presented as the relative increase over unimmunized control mice (n = 3 for all groups). Data show mean + SEM.",
    "ncbi_link": "CCL2: 20296
Cre: 2777477
GM-CSF: 12981
CXCL1: 14825
CXCL10: 15945
CXCL11: 56066
GFAP: 14580
IFN-γ: 15978
IL-17: 16171
IL-6: 16193
NOS2: 18126
OTUB1: 107260
TNF: 21926"
  },
  {
    "caption": "Astrocytes were isolated from unimmunized and diseased OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice at day 15 p.i., respectively. Relative expression of CXCL10, CXCL11, CCL2, and NOS2 mRNA was determined by quantitative real-time PCR. Data are presented as relative increase of genes at day 15 p.i. over gene expression of astrocytes from unimmunized control mice (n = 3 for all groups). Data show mean + SEM.",
    "ncbi_link": "CCL2: 20296
Cre: 2777477
CXCL10: 15945
CXCL11: 56066
GFAP: 14580
NOS2: 18126
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes isolated from OTUB1fl/fl (n = 3) and GFAP-Cre OTUB1fl/fl (n = 3) mice were left untreated or stimulated with IFN-γ (10 ng/ml), IL-17 (50 ng/ml), and TNF (10 ng/ml), respectively, for 16 h. mRNA levels of CXCL10, CXCL11, CCL2, and NOS2 were detected by quantitative real-time PCR.",
    "ncbi_link": "CCL2: 20296
Cre: 2777477
CXCL10: 15945
CXCL11: 56066
GFAP: 14580
NOS2: 18126
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were treated with IFN-γ (10 ng/ml) for indicated times and analyzed by western blot with indicated antibodies.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were treated with IFN-γ (10 ng/ml) for indicated times. Cytoplasmic and nuclear extracts were separated and analyzed by WB with indicated antibodies.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Astrocytes were selectively isolated by MACS from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice at days 0 and 15 p.i., respectively. Relative expression of STAT1 mRNA was determined by quantitative real-time PCR. Data show the relative increase of STAT1 mRNA over that of unimmunized control mice (n = 3 for all groups) (mean + SEM).",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260
STAT1: 20846"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl (n = 3) and GFAP-Cre OTUB1fl/fl (n = 3) mice were stimulated with IFN-γ (10 ng/ml) for indicated times. mRNA was isolated and analyzed by quantitative real-time PCR for SOCS1. Data show the relative increase over untreated controls (mean + SEM).",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were left untreated or treated with IFN-γ (10 ng/ml) for 30 min. Proteins were immunoprecipitated with anti-SOCS1 antibody and analyzed by WB for SOCS1, OTUB1, and K48 Ubiquitin.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes from GFAP-Cre OTUB1fl/fl mice were cotransfected with SOCS1-MYC, K48 ubiquitin-HA, and OTUB1-GFP/OTUB1-∆N-GFP/OTUB1-C91S-GFP plasmids. Twenty-four hours after transfection, cells were left untreated or stimulated with IFN-γ (10 ng/ml) for 30 min before lysation. Proteins were immunoprecipitated with anti-MYC antibody and analyzed by WB for MYC, GFP, and HA.",
    "ncbi_link": "GFP: 
HA: 
MYC: 
Cre: 2777477
GFAP: 14580
OTUB1: 107260
SOCS1: 12703
ubiquitin: 22190///22187///22186///78294"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were transfected with SOCS1-MYC plasmids. Twenty-four hours after transfection, cells were treated with cycloheximide (CHX, 100 μg/ml) for indicated times. SOCS1 protein levels were analyzed by WB (upper panel). The lower panel shows the relative protein levels of SOCS1 normalized to Tubulin (n = 3 for both groups).",
    "ncbi_link": "MYC: 
Cre: 2777477
GFAP: 14580
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from GFAP-Cre OTUB1fl/fl mice were transfected with SOCS1-MYC plasmids or cotransfected with SOCS1-MYC + OTUB1-GFP plasmids. Twenty-four hours after transfection, cells were treated with CHX (100 μg/ml) for indicated times. SOCS1 protein levels were analyzed by WB (upper panel). The lower panel shows the relative protein levels of SOCS1 normalized to Tubulin (n = 3 for both groups) (mean + SEM).",
    "ncbi_link": "GFP: 
MYC: 
Cre: 2777477
GFAP: 14580
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from GFAP-Cre OTUB1fl/fl mice were cotransfected with SOCS1-MYC and OTUB1-GFP/OTUB1-∆N-GFP/OTUB1-C91S-GFP plasmids. Twenty-four hours after transfection, cells were treated with CHX (100 μg/ml) for indicated times. SOCS1 protein levels were analyzed by WB (left panel). The right panel shows the relative protein levels of SOCS1 normalized to Tubulin (n = 4 for both groups). Data represent mean + SEM.",
    "ncbi_link": "GFP: 
MYC: 
Cre: 2777477
GFAP: 14580
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were stimulated with IFN-γ (10 ng/ml) for four hours. Thereafter, cells were treated with CHX (100 μg/ml) for indicated times. Whole cell lysates were analyzed by WB with indicated antibodies.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl mice were transfected with SOCS1-MYC plasmids. Five hours later, astrocytes were subsequently transfected with different siRNAs or left untreated. Twenty-four hours after siRNA transfection, protein was isolated and analyzed by WB for SOCS1 expression.",
    "ncbi_link": "MYC: 
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were transfected with nonsense siRNA and SOCS1 siRNA-2. Twenty-four hours after transfection, cells were stimulated with IFN-γ (10 μg/ml) for 16 hours before mRNA isolation. Quantitative real-time PCR was performed to detect mRNA levels of CXCL10, CCL2, and NOS2 (n = 4 for all groups). Data show mean + SEM.",
    "ncbi_link": "CCL2: 20296
Cre: 2777477
CXCL10: 15945
GFAP: 14580
NOS2: 18126
OTUB1: 107260
SOCS1: 12703"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl and GFAP-Cre OTUB1fl/fl mice were treated with IFN-β (10 ng/ml) for indicated times. Whole cell lysates were analyzed by WB with indicated antibodies.",
    "ncbi_link": "Cre: 2777477
GFAP: 14580
OTUB1: 107260"
  },
  {
    "caption": "Primary astrocytes from OTUB1fl/fl (n = 3) and GFAP-Cre OTUB1fl/fl (n = 3) mice were treated with IFN-β (10 ng/ml) for 16 hours. Quantitative real-time PCR was performed to detect OTUB1 (B), CXCL10 (C), CXCL11 (D), CCL2 (E), and NOS2 (F) mRNA levels. Data show mean + SEM.",
    "ncbi_link": "CCL2: 20296
Cre: 2777477
CXCL10: 15945
CXCL11: 56066
GFAP: 14580
NOS2: 18126
OTUB1: 107260"
  },
  {
    "caption": "(E,F) Expression levels of DEGs relevant to response to hypoxia (left) and blood vessel morphogenesis (right). The values were normalized by tubulin family genes",
    "ncbi_link": "tubulin: "
  },
  {
    "caption": "(I) qPCR levels of HIF-1A in PSCs, normalized to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: 
HIF-1A: 3091"
  },
  {
    "caption": "(A) qPCR levels of LOX-L2 in PSCs, normalized to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: 
LOX-L2: 4017"
  },
  {
    "caption": "(C) Expression of LOX family genes obtained from RNA-seq data in control and tamoxifen treated PSCs (n = 3 experimental replicates). Expression value was normalized by tubulin family genes",
    "ncbi_link": "tubulin: "
  },
  {
    "caption": "(D) qPCR levels of LOX family in PSCs, normalized to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: "
  },
  {
    "caption": "(H) qPCR levels of LOX-L2 and HIF-1A in PSCs, normalized to RPLP0 and relative to 1 kPa",
    "ncbi_link": "RPLP0: 
HIF-1A: 3091
LOX-L2: 4017"
  },
  {
    "caption": "(I) qPCR levels of LOX-L2 and HIF-1A in PSCs, normalized to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: 
HIF-1A: 3091
LOX-L2: 4017"
  },
  {
    "caption": "(K) qPCR levels of LOX-L2 in PSCs, normalized to RPLP0 (60S acidic ribosomal protein P0) and relative to control",
    "ncbi_link": "60S acidic ribosomal protein P0: 
RPLP0: 
LOX-L2: 4017"
  },
  {
    "caption": "(A) qPCR levels of collagen in PSCs, normalized to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: 
collagen: 1278///1277"
  },
  {
    "caption": "(F) qPCR levels of MMP-2 in PSCs, normalized to RPLP0 and relative to contro",
    "ncbi_link": "RPLP0: 
MMP-2: 4313"
  },
  {
    "caption": "(K) qPCR levels of MMP-2 in PSCs, normalized to RPLP0 and relative to 1 kPa",
    "ncbi_link": "RPLP0: 
MMP-2: 4313"
  },
  {
    "caption": "(L) qPCR levels of MMP-2 in PSCs, normalized to RPLP0 and relative to control. Histogram bars represent mean±s.e.m.",
    "ncbi_link": "RPLP0: 
MMP-2: 4313"
  },
  {
    "caption": "(A) qPCR levels of fibronectin (FN), fibronectin extracellular domain A (FN-EDA), and fibronectin extracellular domain B (FN-EDB) in PSCs, normalised to RPLP0 and relative to control",
    "ncbi_link": "RPLP0: 
fibronectin: 2335
FN: 2335"
  },
  {
    "caption": "(A) Bcl-xL was cotransfected into HeLa cells with empty vector (IP negative control), Beclin 1-Flag, Beclin 1-Flag/HA-Bim(EL), Beclin 1-Flag/HA-Puma, Beclin 1-Flag/HA-Noxa, or Beclin 1-Flag/Bad. Anti-Flag (M2) was used for immunoprecipitation, and proteins were detected with anti-Bcl-xL, anti-HA, or anti-Bad, anti-Flag (Rabbit).",
    "ncbi_link": "Bcl-xL: 598
Beclin 1: 8678"
  },
  {
    "caption": "(B) HA-Bim (wild-type) was cotransfected into Bax/Bak double-knockout (DKO) mouse embryonic fibroblasts (MEFs) with empty vector (IP negative control) or Beclin 1-Flag. Immunoprecipitations were performed as in (A).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Beclin 1: 56208"
  },
  {
    "caption": "(C) Beclin 1-Flag was cotransfected into Bax/Bak DKO MEFs with empty vector (IP negative control) or HA-Bim (wild-type). Anti-HA was used for immunoprecipitation. ∗, antibody heavy chain.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(E) Bcl-xL was cotransfected into HeLa cells with empty vector (IP negative control), wild-type HA-Bim(EL), or HA-Bim L152E F159E [Bim(EL)EE]. Anti-Bim was used for immunoprecipitation. ∗, antibody light chain.",
    "ncbi_link": "Bcl-xL: 598
Bim: 10018"
  },
  {
    "caption": "(F) HeLa cells were transfected with vector, wild-type HA-Bim, or HA-BimEE. Lysates were probed with the indicated antibodies. HeLa cells treated with staurosporine (STS) for 5 hr were a positive control. Note that wild-type Bim causes apoptosis, which reduces its levels compared to BimEE.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(G) Vector, wild-type Bim(EL), or Bim(EL) L152E F159E (BimEE) was transfected into HeLa cells. Transfection efficiency was >90%. After 20 hr, cell viability was determined by measurement pf ATP levels. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(H) HeLa cells were transfected with vector/GFP (3:1), wild-type HA-Bim/GFP (3:1), or HA-BimEE/GFP (3:1) (to ensure that Bim-transfected cells also contain GFP). After 16 hr, cells were stained with Annexin V-APC and analyzed by FACS. The percentage of APC and GFP double-positive cells/GFP-positive cells are shown. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(I) Bim(EL)/Bcl-xL were cotransfected into HeLa cells with empty vector (IP negative control) or Beclin 1-Flag; Bim(EL)-EE/Bcl-xL were also cotransfected into HeLa cells with Beclin 1-Flag. Anti-Flag (M2) was used for immunoprecipitation. Data are shown as mean ± SD. NS, not significant.",
    "ncbi_link": "Bcl-xL: 598
Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(J) BimEL-EE (EL)/vector (IP negative control), BimEL-EE (EL)/Beclin 1-Flag, BimL-EE (L)/Beclin 1-Flag, and BimS-EE (S)/Beclin 1-Flag were transfected into HeLa cells. Anti-Flag was used for immunoprecipitation. Data are shown as mean ± SD. ∗∗∗p < 0.001; NS, not significant.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(A) Bim−/− and Bim+/+ MEFs were cultured in 6-well dishes. Cells were treated with vehicle or Bafilomycin A1 (Baf) for 4 hr. Blots were probed with the indicated antibodies. LC3-II/tubulin in wild-type control MEFs is set as 1. The relative value of LC3-II/tubulin in Bim-knockout MEFs is shown (n = 5). Data are mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(C) Bim−/− and Bim+/+ MEFs were transfected with GFP-LC3. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(D) HeLa cells were transfected with control plasmid (pMKO)/GFP-LC3 or pMKO-BimshRNA/GFP-LC3 (to ensure that GFP-LC3-positive cells also contain BimshRNA or control plasmid, the ratio of pMKO or pMKO-BimshRNA/GFP-LC3 is 3:1). The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(E) HeLa cells were transfected with control plasmid (pMKO) or pMKO-BimshRNA. Blots were probed with the indicated antibodies. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(F) HeLa cells were transfected with control plasmid (pMKO)/GFP-PX or pMKO-BimshRNA/GFP-PX (3:1). The percentages of cells with GFP-vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(G) DFCP1-GFP cells were transfected with control siRNA or Bim siRNA. The numbers of GFP puncta were assessed. Data are shown as mean ± SD.∗p < 0.05.Images represent DFCP1-GFP vesicles in cells transfected with control siRNA and Bim siRNA. Arrows mark DFCP1-GFP puncta.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(I) Bim(EL)/control siRNA, Bim(EL)/Bim siRNA, Bim(EL)EE/control siRNA, Bim(EL)EE/Bim siRNA, vector/control siRNA, and vector/Bim siRNA were transfected into HeLa cells. Blots were probed with the indicated antibodies. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(J) HeLa cells were transfected with control plasmid or Bim(EL)EE. Blots were probed with the indicated antibodies. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(K) Bax/Bak DKO MEFs were transfected with control plasmid /GFP-LC3, wild-type Bim(EL)/GFP-LC3 (3:1), or Bim (EL) EE/GFP-LC3. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bim: 12125"
  },
  {
    "caption": "(L) Two independent control vector (pcDNA3) or Bim(EL)EE stably expressing HeLa cell clones were transfected with GFP-LC3 respectively. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(M) HeLa cells were transfected with control plasmid/GFP-PX or Bim(EL)EE/GFP-PX (3:1). The percentages of cells with GFP-vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01. Fluorescent microscope images show GFP-PX vesicles.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(A) Lysates from spleen-derived T cells of wild-type (Bim+/+) and Bim-knockout (Bim−/−) mice were immunoblotted and probed with indicated antibodies. Statistics were from three knockout and control mice. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(B) T cells from Bim+/+ and Bim−/− mice were cultured with/without Baf for 4 hr preceding harvest, immunoblotted, and probed with the indicated antibodies.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(C) Spleen-derived T cells from Bim+/+ or Bim−/− mice were stained with rabbit anti-LC3 antibody. Representative confocal images and quantification from triplicates (n = 100-110) are shown. Data are shown as mean ± SD. ∗∗∗p < 0.0001.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(D) Bim+/+ and Bim−/− mouse liver lysates were immunoblotted and probed with the indicated antibodies (n = 3). Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(E) Bim+/+ and Bim−/− mouse liver lysates were immunoblotted and probed with the indicated antibodies (n = 3). Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 12125"
  },
  {
    "caption": "(F) RNA from Bim wild-type or Bim-knockout mouse livers was analyzed by qRT-PCR for p62/beta-actin mRNA. The mean ± SD from three mice per group is shown. NS, not significant.",
    "ncbi_link": "beta-actin: 
Bim: 12125
p62: 18412"
  },
  {
    "caption": "(A) HeLa cells were treated with control siRNA, Bim siRNA + control siRNA, control siRNA + Beclin 1 siRNA, or Bim siRNA + Beclin 1 siRNA. Blots were probed as indicated. Data are shown as mean ± SD. ∗∗p < 0.01.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(B) HeLa cells were treated with control siRNA, Bim siRNA + control siRNA, control siRNA + Beclin 1 siRNA, or Bim siRNA + Beclin 1 siRNA. After 24 hr, cells were transfected with GFP-PX for 24 hr. GFP-PX vesicles were assessed with a confocal microscope. Data are shown as mean ± SD. ∗∗p < 0.01. Arrows label cells with increased number/size of GFP-PX vesicles.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(C) GFP-mRFP-LC3 HeLa cells were treated with control, Bim siRNA, or Bcl-2 siRNA and then analyzed with Cellomics microscope. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bcl-2: 596
Bim: 10018"
  },
  {
    "caption": "(D) GFP-mRFP-LC3 stable HeLa cells were treated with control siRNA, Bim siRNA + control siRNA, control siRNA + Beclin 1 siRNA, or Bim siRNA + Beclin 1 siRNA and then analyzed with Cellomics microscope and matching confocal images are shown. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(A) Bim(EL)EE/empty vector (IP negative control) or Bim(EL)EE/Beclin 1-Flag (in duplicate) were transfected into HeLa cells. After 20 hr, one set of cells with Bim(EL)EE/Beclin 1-Flag were starved in HBSS for 2 hr. Anti-Flag antibody (M2) was used for immunoprecipitation, and blots were probed as indicated. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(B) Panel i: HeLa cells were treated with control siRNA or Bim siRNA. After 48 hr, one set of transfections were starved in HBSS for 2 hr. Blots were probed as indicated. LC3-II/tubulin ratio of siRNA-transfected cells is set as 1 (n = 3). Data are shown as mean ± SD. ∗∗∗p < 0.001; NS, not significant. Panel ii: HeLa cells were treated with control siRNA or Bim siRNA. After 48 hr, one set of transfections were treated with Baf for 2 hr; one set of transfections were starved and treated with Baf for 2 hr. Blots were probed as indicated and analyzed as in (Bi). ∗∗p < 0.01; NS, not significant.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(C) HeLa cells were transfected with control plasmid /GFP-LC3 (3:1), or Bim(EL)EE/GFP-LC3 (3:1). After 20 hr, one set of transfected cells were starved in HBSS for 2 hr and then fixed. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01. NS, not significant.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(D) BimS-Beclin 1 binding is not sensitive to HBSS starvation. BimEL-EE (EL)/vector (IP negative control), BimEL-EE (EL)/Beclin 1-Flag (two replicates), BimL-EE (L)/Beclin 1-Flag (two replicates) or BimS-EE (S)/Beclin 1-Flag (two replicates) were transfected into HeLa cells. After 20 hr, one of EL-Beclin 1-Flag transfections, one of L-Beclin-Flag transfections and one of S-Beclin 1-Flag transfections were subjected to 2 hr HBSS starvation. Anti-Flag (M2) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(E) HBSS starvation increases Bim T116 phosphorylation. Bim(EL)EE or BimEE(EL)-T116A were transfected into HeLa cells. After 20 hr, one set of Bim(EL)EE transfections and one of Bim(EL)EE-T116A were starved for 2 hr in HBSS. Blots were probed with the indicated antibodies.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(F) Bim T116 phosphorylation disables Bim-Beclin 1 interaction. Bim(EL)EE /vector (IP negative control), Bim(EL)EE/Beclin 1-Flag (in duplicate), or Bim(EL)EE-T116E (phospho-mimic, designated as T116E here)/Beclin-Flag (in duplicate) were transfected into HeLa cells. After 20 hr, one set of Bim(EL)EE/Beclin 1-Flag transfections and one of Bim(EL)EE-T116E/Beclin 1-Flag transfections were starved for 2 hr in HBSS (Starv). Anti-Flag (M2) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(G) HeLa cells were transfected with control plasmid /GFP-LC3, Bim(EL)-EE/GFP-LC3 (3:1), or Bim(EL)-EE T116E/GFP-LC3 (3:1). After 20 hr, one set of transfected cells were starved in HBSS for 2 hr and the cells were then fixed. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01; NS, not significant.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(A) Bim-147 does not bind to Beclin 1. Beclin 1-Flag/vector (IP negative control), Beclin 1-Flag/Myc-BimEL-1-147aa (Myc-147), or Beclin 1-Flag/Myc-BimEL-ΔBH3 (Myc-ΔBH3) were transfected into HeLa cells. Anti-Myc (Rabbit) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678"
  },
  {
    "caption": "(B) Bim-147 is competent for LC8 binding. LC8/vector (IP negative control), LC8/Myc-BimEL-1-147aa (Myc-147), or LC8/Myc-BimEL-ΔBH3 (Myc-ΔBH3) were transfected into HeLa cells. Anti-Myc (Rabbit) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
LC8: 8655"
  },
  {
    "caption": "(C) Mutating LC8 binding consensus sites within Bim disrupts the Bim-LC8 interaction. Bim(EL)EE/vector (IP negative control), Bim(EL)EE/Myc-LC8, Bim(EL)EE-S109A, S113A, T114A (AAA)/ Myc-LC8, or Bim(EL)EE-T116E/ Myc-LC8 were transfected into HeLa cells. Anti-Myc (Rabbit) was used for immunoprecipitation. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
LC8: 8655"
  },
  {
    "caption": "(D) Mutating LC8 binding consensus sites within Bim disrupts the Bim-Beclin 1 interaction. Bim(EL)EE/vector (IP negative control), Bim(EL)EE/Beclin 1-Flag, Bim(EL)EE-S109A, S113A, T114A (AAA)/Beclin 1-Flag, or Bim(EL)EE-T116E/Beclin 1-Flag were transfected into HeLa cells. Anti-Flag (M2) was used for immunoprecipitation. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678
LC8: 8655"
  },
  {
    "caption": "(E) Bim-S does not bind to LC8. BimEL-EE (EL)/vector (IP negative control), BimEL-EE (EL)/Myc-LC8, BimL-EE (L)/Myc-LC8, or BimS-EE (S)/Myc-LC8 were transfected into HeLa cells. Anti-Myc (Rabbit) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
LC8: 8655"
  },
  {
    "caption": "(G) LC8 enhances Bim-Beclin 1 interaction in vitro. His-Bim, His-LC8 and GST-Beclin 1 were expressed in BL21(DE3) E. coli and purified. Two micrograms of His-Bim was combined with 2 μg GST without or with 1 μg His-LC8 (as controls); 2 μg His-Bim was combined with 2 μg GST-Beclin 1 without or with 1 μg His-LC8. The mixtures were incubated in buffer A for 3 hr. Glutathione beads were then used to pull down GST or GST-Beclin 1. The pulldown products were detected with anti-Bim and anti-Beclin 1.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678
LC8: 8655"
  },
  {
    "caption": "(H) LC8 siRNA knockdown reduces the Bim-Beclin 1 interaction. Control siRNA or LC8 siRNA were transfected into HeLa cells. After 48 hr, HA-Bim(EL)EE/vector (IP negative control) or HA-Bim(EL)EE/Beclin 1-Flag was transfected into control siRNA transfected HeLa cells; HA-Bim(EL)EE/Beclin 1-Flag was transfected into LC8 siRNA-transfected HeLa cells. Anti-Flag (M2) was used for immunoprecipitation. Note that in the presence of BimEE, endogenous LC8 was pulled down by Beclin 1 when cells were treated with control siRNA. Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678
LC8: 8655"
  },
  {
    "caption": "(A) HeLa cells were transfected with vector (vec) /GFP-LC3, BimEL-EE (EL)/GFP-LC3, BimL-EE (L)/GFP-LC3, BimS-EE (S)/GFP-LC3, or BimEL-EE-AAA (AAA)/GFP-LC3 (3:1). The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗∗p < 0.001; ∗∗p < 0.01; NS, not significant. Note that BimEL-EE-S109A, S113A, T114A is designated as BimEL-EE-AAA.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(B) Bim bridges the Beclin 1-LC8 interaction. Dynein light chain1 (Myc-LC8)/empty vectors (IP negative control), Myc-LC8/Beclin 1-Flag/empty vector, Myc-LC8/Beclin 1-Flag/BimEL-EE (EL), Myc-LC8/Beclin 1-Flag/BimL-EE (L), Myc-LC8/Beclin 1-Flag/BimS-EE (S), and Myc-LC8/Beclin 1-Flag/BimEL-EE-S109A, S113A, T114A (AAA) were transfected into HeLa cells. Anti-Flag (M2) was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678
Dynein light chain1: 8655
LC8: 8655"
  },
  {
    "caption": "(C) Starvation reduces the ability of Bim to bridge the Beclin 1-LC8 interaction. Myc-LC8/empty vectors (IP negative control), Myc-LC8/Beclin 1-Myc/empty vector, or Myc-LC8/Beclin 1-Flag/HA-BimEL-EE (HA-Bim) (two replicates) were transfected into HeLa cells. After 20 hr, one set of cells with Myc-LC8/Beclin 1-Flag/HA-HA-Bim was starved in HBSS for 2 hr. Anti-Flag (M2) antibody was used for immunoprecipitation.",
    "ncbi_link": "Bim: 10018
Beclin 1: 8678
LC8: 8655"
  },
  {
    "caption": "(E) HeLa cells were treated with control siRNA or LC8 siRNA. After 24 hr, cells were split. Vector/GFP-LC3 or Bim(EL)EE/GFP-LC3 (3:1) were transfected into the control siRNA-transfected or LC8 siRNA-transfected cells. The percentages of cells with GFP-LC3 vesicles were assessed. Data are shown as mean ± SD. ∗∗p < 0.01; NS, not significant.",
    "ncbi_link": "Bim: 10018
LC8: 8655"
  },
  {
    "caption": "(F) HeLa cells were treated with control siRNA, Bim siRNA, or LC8 siRNA for 48 hr. Cells were then fixed in 37°C, 4% PFA for 10 min. Cells were stained with Beclin 1 and tubulin antibodies and analyzed by confocal microscopy. White boxes/triangle show areas where Beclin 1 is enriched. Yellow boxes show enlarged areas. Colocalizations were quantified from images in 12-15 cells with Volocity program (Colocalization coefficient Mx). Data are shown as mean ± SD. ∗∗∗p < 0.001.",
    "ncbi_link": "Bim: 10018
LC8: 8655"
  },
  {
    "caption": "L U2OS cells stably expressing CB-GFP or CB-Bub1-K-GFP were treated as in (H). Example images of the immunofluorescence staining are shown.",
    "ncbi_link": "GFP: 
Bub1: 699
CB: 1059"
  },
  {
    "caption": "U2OS cells stably expressing CB-GFP, CB-Bub1-K-GFP or CB-Bub1-K-D946N-GFP were transfected with siRNA, and subjected to immunofluorescence staining with DAPI and the antibodies for H2ApT120 and TOP2A (A). Data information: Scale bars, 10 μm.",
    "ncbi_link": "GFP: 
Bub1: 699
CB: 1059"
  },
  {
    "caption": "U2OS cells stably expressing CB-GFP, CB-Bub1-K-GFP or CB-Bub1-K-D946N-GFP were transfected with siRNA Lysates of nocodazole-arrested mitotic cells were immunoblotted (B). * represents non-specific bands.",
    "ncbi_link": "GFP: 
Bub1: 699
CB: 1059"
  },
  {
    "caption": "B U2OS cells stably expressing CB-GFP, CB-Bub1-K-GFP or CB-Bub1-K-D946N-GFP were subjected to immunofluorescence staining. Example images of anaphase cells are shown. Data information: Scale bars, 10 μm.",
    "ncbi_link": "GFP: 
Bub1: 699
CB: 1059"
  },
  {
    "caption": "C U2OS cells stably expressing CB-GFP, CB-Bub1-K-GFP or CB-Bub1-K-D946N-GFP were subjected to immunofluorescence staining with DAPI, and antibodies for TOP2A and H2ApT120 or H3pS10. Example images of interphase cells are shown. The cells in the top line, which is H3pS10-positive, are in early prophase/late G2. Data information: Scale bars, 10 μm.",
    "ncbi_link": "GFP: 
Bub1: 699
CB: 1059"
  },
  {
    "caption": "D U2OS-LacO cells transiently expressing EGFP-LacI, EGFP-LacI-Bub1-K (WT or D946N) were subjected to immunofluorescence staining. Arrows point to the transgene loci. Data information: Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Bub1: 699"
  },
  {
    "caption": "A, B HeLa cells and the Sgo1-K492A mutant cells were immunostained with the indicated antibodies. Example images are shown (A). The immunofluorescence intensity ratio of centromeric INCENP/ACA was determined on around 250 chromosomes in 10 cells (B). Data information: Means and error bars representing S.D. are shown ; unpaired t-test). Scale bars, 10 μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "C, D HeLa and the Sgo1-K492A cells were exposed to nocodazole for 4 hr. Mitotic cells were cytospun onto coverslips and fixed for immunostaining. Example images are shown (C). The immunofluorescence intensity ratio of centromeric TOP2A/arm TOP2A was determined on around 150 chromosomes in 10 cells (D). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "E, F HeLa and the Sgo1-K492A cells were transfected with siRNA, and immunostained with the indicated antibodies. Example images are shown (E). The immunofluorescence intensity ratio of centromeric Aurora B/ACA was determined on around 250 chromosomes in 10 cells (F). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "G, H HeLa and the Sgo1-K492A cells were transfected with siRNA, and treated with nocodazole for 5 hr. Mitotic cells were cytospun onto coverslips and fixed for immunostaining. Example images are shown (G). The immunofluorescence intensity ratio of centromeric TOP2A/arm TOP2A was determined on around 280 chromosomes in 10 cells (H). Data information: Means and error bars representing S.D. are shown unpaired t-test). Scale bars, 10 μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "HeLa cells transiently expressing EGFP-TOP2A (970-1531) or EGFP-TOP2A (970-1531)-Δ(1015-1032) were treated and immunostained Example images are shown (G). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells transiently expressing EGFP-TOP2A (970-1531) or EGFP-TOP2A (970-1531)-Δ(1015-1032) were treated and immunostained The immunofluorescence intensity ratio of centromeric EGFP-TOP2A/arm EGFP-TOP2A was determined on around 250 chromosomes in 10 cells (H). Data information: Means and error bars representing S.D. are shown unpaired t-test).",
    "ncbi_link": "EGFP: 
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1 and EGFP-TOP2A (970-1531) were subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and GFP. Example images are shown (I). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1 and EGFP-TOP2A (970-1531) were subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and GFP. The relative enrichment of EGFP-TOP2A at the LacO repeats was quantified in 130 cells (J). Data information: Means and error bars representing S.D. are shown unpaired t-test).",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1 and EGFP-TOP2A (970-1531) were subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and GFP. Cell lysates were immunoblotted (K).",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1 and the indicated EGFP-TOP2A proteins were subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and H2ApT120. Example images are shown (B). The relative enrichment of EGFP signal at the LacO repeats was quantified in 30 cells (C). Arrows point to the transgene loci. Data information: Means and error bars representing S.D. are shown ; unpaired t test). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1 and the indicated EGFP-TOP2A proteins Cell lysates were immunoblotted (D).",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS cells stably expressing the indicated CENP-B fusion proteins were transfected with the plasmid encoding TOP2A-Myc-6xHis or TOP2A-ΔChT-Myc-6xHis, and then subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and H2ApT120. Example images are shown (I). Scale bars, 10 μm.",
    "ncbi_link": "His: 
Myc: 
CENP-B: 1059
TOP2A: 7153"
  },
  {
    "caption": "U2OS cells stably expressing the indicated CENP-B fusion proteins were transfected with the plasmid encoding TOP2A-Myc-6xHis or TOP2A-ΔChT-Myc-6xHis, and then subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and H2ApT120. The relative enrichment of anti-Myc staining signal at the centromere region versus that in the nearby nuclear region was quantified on around 200 chromosomes in 10 cells (J). Data information: Means and error bars representing S.D. are shown unpaired t test).",
    "ncbi_link": "His: 
Myc: 
CENP-B: 1059
TOP2A: 7153"
  },
  {
    "caption": "U2OS cells stably expressing the indicated CENP-B fusion proteins were transfected with the plasmid encoding TOP2A-Myc-6xHis or TOP2A-ΔChT-Myc-6xHis, and then subjected to immunofluorescence staining with DAPI and antibodies for the Myc-tag and H2ApT120. Cell lysates were immunoblotted (K).",
    "ncbi_link": "His: 
Myc: 
CENP-B: 1059
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells with or without transient expression of H2B-GFP or EGFP-TOP2A were exposed to nocodazole for 3 hr. Mitotic cells were cytospun onto coverslips and subjected to immunofluorescence staining with DAPI and antibodies for GFP, Sgo1 and ACA. Example images are shown (A). The immunofluorescence intensity ratio of centromeric Sgo1/ACA was determined on 400 chromosomes in 20 cells (B). The means and S.D.s from three independent experiments with the Sgo1/ACA ratio determined on around total 1200 chromosomes in 60 cells are shown (C). Data information: Means and error bars representing S.D. are shown unpaired t test). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
GFP: 
H2B: 8349///440689///100288742///100820735///114483833///767811///337872///10340///100101478///338391///337875
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells with or without transient expression of H2B-GFP or EGFP-TOP2A were exposed to nocodazole for 3 hr. Mitotic cells were cytospun onto coverslips and Lysates of asynchronous cells were immunoblotted (D). * represents non-specific bands.",
    "ncbi_link": "EGFP: 
GFP: 
H2B: 8349///440689///100288742///100820735///114483833///767811///337872///10340///100101478///338391///337875
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1, with or without EGFP-TOP2A (970-1531), were subjected to immunofluorescence staining with DAPI and antibodies for H2ApT120 and Sgo1. Example images are shown (E). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1, with or without EGFP-TOP2A (970-1531), were subjected to immunofluorescence staining with DAPI and antibodies for H2ApT120 and Sgo1. The relative enrichment of EGFP-TOP2A (F) and Sgo1 (G) at the LacO repeats was quantified in 120 cells. Data information: Means and error bars representing S.D. are shown unpaired t test).",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing Myc-LacI-Bub1, with or without EGFP-TOP2A (970-1531) Cell lysates were immunoblotted (H).",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
Myc: 
Bub1: 699
TOP2A: 7153"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing EGFP-LacI-Bub1-K together with VSV-Sgo1 or a control vector were subjected to immunofluorescence staining with DAPI and antibodies for TOP2A and VSV-tag. Example images are shown (I). The relative enrichment of TOP2A (J) and VSV-Sgo1 (K) at the LacO repeats was quantified in 50 cells. Data information: Means and error bars representing S.D. are shown unpaired t test). Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
VSV: 
Bub1: 699
Sgo1: 151648"
  },
  {
    "caption": "U2OS-LacO cells transiently expressing EGFP-LacI-Bub1-K together with VSV-Sgo1 or a control vector Cell lysates were immunoblotted (L). * represents non-specific bands.",
    "ncbi_link": "EGFP: 
LacI: 
LacO: 
VSV: 
Bub1: 699
Sgo1: 151648"
  },
  {
    "caption": "HeLa and the Sgo1-K492A cells transfected with the indicated siRNA were synchronized and treated with BAY 1816032 or DMSO and then immunostained with the indicated antibodies. Example images of anaphase cells are shown (H). The percentage of anaphases with PICH was determined in at least 256 cells in each condition. Means and S.D.s from three independent experiments are shown (I). Example images of prometaphase cells immunostained with the indicated antibodies are shown (J). Data information: Means and error bars representing S.D. are shown unpaired t test). Scale bars, 10 μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "HeLa and the Sgo1-K492A cells transfected with the indicated siRNA were synchronized and treated with BAY 1816032 or DMSO Lysates of nocodazole-arrested mitotic cells were immunoblotted (K).",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "A HeLa cells were transfected with plasmids encoding CB-GFP or CB-TOP2A-GFP. Lysates of asynchronously growing cells were immunoblotted with the indicated antibodies.",
    "ncbi_link": "GFP: 
CB: 1059
TOP2A: 7153"
  },
  {
    "caption": "E, F HeLa cells transiently expressing CB-GFP or CB-TOP2A-GFP were released from single thymidine block, and after 7 hr, BAY 1816032 or DMSO was added for 5 hr. Cells were then fixed and subjected to immunofluorescence staining as in (B). Example images of anaphase cells are shown (E). The percentage of anaphases with PICH was determined in at least 142 cells in each condition. Means and S.D.s from three independent experiments are shown (F). Arrows point to the UFBs. Data information: Means and error bars representing S.D. are shown ; unpaired t test). Scale bars, 10 μm.",
    "ncbi_link": "GFP: 
CB: 1059
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells transfected with siRNA and plasmids encoding EGFP-TOP2A (WT or ΔChT) were synchronized and then subjected to immunofluorescence staining with DAPI, ACA and the antibodies for PICH and GFP. Example images of anaphase cells are shown (G). Arrows point to the UFBs. Scale bars, 10 μm.",
    "ncbi_link": "EGFP: 
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells transfected with siRNA and plasmids encoding EGFP-TOP2A (WT or ΔChT) were synchronized and then subjected to immunofluorescence staining with DAPI, ACA and the antibodies for PICH and GFP. The percentage of anaphases with PICH was determined in at least 174 cells in each condition. Means and S.D.s from three independent experiments are shown (H). Data information: Means and error bars representing S.D. are shown unpaired t test).",
    "ncbi_link": "EGFP: 
TOP2A: 7153"
  },
  {
    "caption": "HeLa cells transfected with siRNA and plasmids encoding EGFP-TOP2A (WT or ΔChT) were synchronized and then Lysates of asynchronous cells were immunoblotted (I).",
    "ncbi_link": "EGFP: 
TOP2A: 7153"
  },
  {
    "caption": "C. The reported mutagenesis data on MCP CCP3 and CCP4 (data from Liszewki et al. (Liszewski et al, 2000)) are consistent with the crystal structure. Shown are two orientations of the surface of MCP CCP3-4 as in the crystal structure of the C3b-MCP complex, highlighting the contact sites with the C3b platform (purple), the MCP mutations identified as critical for C3b binding (red) and those not affecting the interaction (blue). The GB24 antibody epitope is shown as yellow contour on the MCP surface.",
    "ncbi_link": "MCP: 4179"
  },
  {
    "caption": "(A) Mapping of known disease-related mutations on C3b (Table 3). The high-resolution C3b three-dimensional structure is used as structural template, shown as white surface. The regulator contact surfaces (based on C3b-FH (CCP1-4) (Wu et al, 2009) and C3d-FH (CCP19-20) (Kajander et al, 2011; Morgan et al, 2011)) are shown as black contour. All mutations reported in Table 3 are shown in blue on the C3b surface. Disease-related mutants reported to affect regulator binding are shown in red and labeled in the right magnified panel.",
    "ncbi_link": "C3b: 718"
  },
  {
    "caption": "G Volcano plot illustrating proteins significantly under- or over-represented in sg-CTRL and sg-HMGCL PANC-1 spheroids (n=3 independent experiments). Significance was defined by one-tailed Student's t-test. Protein levels with a q-value<0.05 (horizontal axis) and a fold change <-1.5 or >+1.5 (vertical axis) are considered as significantly down or up-regulated in sg-HMGCL PANC-1 spheroids.",
    "ncbi_link": "HMGCL: 3155"
  },
  {
    "caption": "A, B Quantification of volume with representative images (A) and weight (B) of sg-CTRL (n=15 for A and n=9 for B), sg HMGCL #2 (n=19 for A and n=8 for B), #3 (n=7 for A and B) pancreatic tumors. Data are expressed as mean of  tumor volume or weight ± SEM. Significance was defined by Mann-Whitney test. *: p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "HMGCL: 3155"
  },
  {
    "caption": "C Extracellular matrix  quantification following  trichrome  staining in sg-CTRL and sg-HMGCL #2 pancreatic tumors sections (n=8 and 9 mice/group respectively, left panel). Data are expressed as mean of percentage of total tissue area ± SEM. Significance was defined by Mann-Whitney test. **: p<0.01. Representative images of  trichrome staining in sg-CTRL and sg-HMGCL pancreatic tumors. Scale bar: 100 µm (right panel).",
    "ncbi_link": "HMGCL: 3155"
  },
  {
    "caption": "D, E Quantification of  volume (D) and weight (E) of sg-CTRL pancreatic tumors treated with 0.9% NaCl (i.p.) (n=4), and pancreatic tumors from two different clones of sg-HMGCL treated with 0.9% NaCl (i.p.) or βOHB (100mg/kg/bi-weekly, i.p.) (n=10/group). Data are expressed as mean of  tumor volume or  weight ± SEM. Significance was defined by Mann-Whitney test. ns: not significant, **p<0.01.",
    "ncbi_link": "HMGCL: 3155"
  },
  {
    "caption": "H [U-13C]βOHB  tracing into TCA intermediate: citrate in sg-CTRL and sg-HMGCL #2 and #3 PANC-1 cells cultured in indicated glucose concentrations. Data are expressed as mean ± SEM. (n=2 independent experiments). Significance was defined by one-way ANOVA followed by a Bonferroni's multiple comparisons test, only significances between sg-HMGCL #2, #3 PANC-1 cells and sg-CTRL PANC-1 cells under the same culture condition are mentioned. ***p<0.001.",
    "ncbi_link": "HMGCL: 3155"
  },
  {
    "caption": "(c) Shown are the responses of the glucose sensor promoter (PgluA7), a negative control lacking the CRP operator (PgluA7*), and a constitutive promoter (BBa_J23101) to the presence (+) and absence (-) of glucose",
    "ncbi_link": "BBa_J23101: 
PgluA7: 
sensor: "
  },
  {
    "caption": "(d) Shown are the responses of the oxygen sensor promoter (PfnrF8), a negative control lacking the FNR operator (PfnrF8*), and a constitutive promoter (BBa_J23101) to the presence (+) and absence (-) of oxygen",
    "ncbi_link": "BBa_J23101: 
PfnrF8: 
sensor: "
  },
  {
    "caption": "Shown are the schematics and responses for the glucose sensor The response functions (center) are shown for each sensor (black circles) compared to promoter variants where the operators are removed (PgluA7*, PfnrF8*) (open circles) text). Representative cytometry florescence distributions for Figures 1f",
    "ncbi_link": "PfnrF8: 
PgluA7: 
sensor: "
  },
  {
    "caption": "Shown are the schematics and responses for th oxygen sensors Horizontal error bars in the PfnrF8 response reflect one standard deviation of three DO measurements Representative cytometry florescence distributions for Figure 1g",
    "ncbi_link": "PfnrF8: 
sensors: "
  },
  {
    "caption": "Shown are the schematics and responses for th acetate sensors For the acetate sensor, the response of the sensor is shown in unmodified E. coli MG1655 with glnL intact (open diamonds). The dynamics of induction are shown (right graph) where cells are induced at the time indicated by the dashed line (see text). Representative cytometry florescence distributions for Figure 1h are shown i",
    "ncbi_link": "sensor: 
sensors: "
  },
  {
    "caption": "The responses of the glucose sensors during growth in shake flasks are shown",
    "ncbi_link": "sensors: "
  },
  {
    "caption": "The responses of th e, oxygen sensors during growth in shake flasks are shown",
    "ncbi_link": "sensors: "
  },
  {
    "caption": "The responses of th acetate sensors during growth in shake flasks are shown",
    "ncbi_link": "sensors: "
  },
  {
    "caption": "(e) The responses of a 3-input, 2-output circuit are shown. (f) Shown are the circuit (left) and genetic diagram (right) of the circuit corresponding to part e. In the genetic diagram, the dashed line and * indicates a second copy of the PgluA7 promoter that drives rfp expression and is repressed by PhlF via an immediately downstream PhlF operator. (g) The response of the circuit in parts e and f to different combinations of stimuli under the same conditions as Figure 1 (Methods). The (+) and (-) indicate whether the output promoter of each sensor is active under those conditions. Bars where the circuit is predicted to be on are shown in grey and white when predicted to be off",
    "ncbi_link": "PgluA7: 
PhlF: 
sensor: "
  },
  {
    "caption": "(b) Reduction of fluorescence of RFP by the different mechanisms of repression after 18 hours of growth (Methods). The inducers are either 1 mM IPTG (sRNA) or 25 μM DAPG (sgRNA, mf-LON). sgRNA and mf-LON are co-transcribed on a single transcript, processed by ribozymes (Appendix Figure S13). (c) The dynamics of repression by each of the mechanisms is shown. Empty circles are uninduced and black circles are induced (1 mM IPTG or 25 µM DAPG) at the 2-hour time point (dashed line) (Methods)",
    "ncbi_link": "LON: "
  },
  {
    "caption": "(f) The impact on acetate production for a double mutant where poxB is complemented on a BAC (Methods). Note that complementation causes a ~3-fold reduction in acetate compared to WT in part d. N-ter and E170 refer to the location of the SuMMV tag. (g) Reduction of acetate production by the expression of SuMMV from an DAPG-inducible promoter (- no inducer, + 25 µM). The PoxB variant with the degron inserted at position E170 is either carried on a BAC or at its native location in the genome",
    "ncbi_link": "SuMMV: 
poxB: 946132
PoxB: 946132"
  },
  {
    "caption": "(b) The transcription of poxB over time (E. coli MG1655∆glnL), as calculated from RNA-seq data (Methods). The colored bars indicate the times at which the glucose/acetate sensors will be on based on metabolite measurements. It should be noted that these are right-shifted compared to Figure 2 due to slower growth of the tested strains",
    "ncbi_link": "sensors: 
glnL: 948360
poxB: 946132"
  },
  {
    "caption": "(c) The production of acetate is shown over time for E. coli MG1655∆glnL∆pta poxB::E170 (black) as compared to the same strain containing the complete circuit (green). A version of the circuit in which the sgRNA is targeted to rfp (not present in the system) and is tested in MG1655∆glnL∆pta containing an untagged poxB as a control (red). Empty circles connected by the dashed line represent MG1655∆glnL∆pta∆poxB",
    "ncbi_link": "glnL: 948360
poxB: 946132
pta: 946778"
  },
  {
    "caption": "(e) The transcription of pta over time (E. coli MG1655∆glnL), as calculated from RNA-seq data (Methods). The colored bars indicate the times at which the glucose/oxygen sensors will be on based on metabolite measurements",
    "ncbi_link": "sensors: 
glnL: 948360
pta: 946778"
  },
  {
    "caption": "(f) The production of acetate is shown over time for E. coli MG1655∆glnL∆poxB pta::pdt3 as compared to a strain containing the complete circuit (green) tested in same strain. A version of the circuit in which the sgRNA is targeted to rfp (not present in the system) and is tested in MG1655∆glnL∆poxB containing an untagged pta as a control (red) Empty circles connected by the dashed line represent MG1655∆glnL∆pta∆poxB",
    "ncbi_link": "glnL: 948360
poxB: 946132
pta: 946778"
  },
  {
    "caption": "(H, I) Enzymatic activity of FBL is not required for cell proliferation. Colony formation assays were conducted to investigate the role of enzymatic activity in cell proliferation. FBL knockdown HCT116 or A549 cells with ectopic expression of FBL or the catalytically inactive mutant (FBL-E191A/ D236A) were used, with a bar graph showing the relative number of colonies per well (mean ± SD). All cells were allowed to form colonies for 10 days and representative images of colonies in plates stained with Giemsa were displayed. The bar graphs present data as mean ± SD from three independent experiments. The statistical significance was determined using one-way ANOVA. ns denotes no statistical significance, * indicates P < 0.05, *** indicates P < 0.001.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(A, B) Knockdown of FBL results in increased cellular sensitivity to DNA damage treatment. Cell viability analysis was performed on control (shNC) and shFBL-HCT116/shFBL-A549 cells treated with indicated concentrations of 5 μM MMC using CCK-8 assays. Each data point represents the mean ± SD from three replicates. The statistical significance was determined using Student's t-test. ***p < 0.001.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(D-F) Immunofluorescence staining showed the formation of γH2AX and BRCA1 foci in shFBL and shNC HCT116 cells treated with 5 μM MMC or mock treatment. The scale bar represents 10 μm. The (E) and (F) panel displays quantification of the (D) panel: indicating the number of γH2AX or BRCA1 foci per cell (n≥100 cells). Data are shown as the mean ± SD. The statistical significance was determined using one-way ANOVA, with ns indicating no statistical significance, *** indicating P < 0.001.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(B). Co-IP analyses of GFP- tagged FBL and SFB-tagged YBX1 in HCT116 cells using indicated antibodies. HCT116 cells were transfected with vectors encoding GFP-FBL and SFB-YBX1. Cells were lyzed with NETN300 buffer. Cell extracts were examined by IP and western blot with indicated antibodies.",
    "ncbi_link": "GFP: 
FBL: 2091
YBX1: 4904"
  },
  {
    "caption": "(E) The N-terminal GAR domain is essential for the interaction between FBL and YBX1. Upper panel, a schematic representation of wild-type FBL with the GAR domain and methyltransferase domain (MTase). Lower panel, Co-IP analyses of GFP-tagged FBL deletion mutants and SFB-tagged YBX1 in HCT116 cells.",
    "ncbi_link": "GFP: 
FBL: 2091
YBX1: 4904"
  },
  {
    "caption": "(F) The B/A repeat domain of YBX1 is essential for the interaction between YBX1 and FBL. Upper panel, a schematic representation of wild-type YBX1 with the Alanine/proline rich domain, Cold shock domain and B/A repeat domain. Lower panel, co-IP analyses of GFP-tagged YBX1 deletion mutants and SFB-tagged FBL in HCT116 cells.",
    "ncbi_link": "GFP: 
FBL: 2091
YBX1: 4904"
  },
  {
    "caption": "(C) Subcellular localization of YBX1/FBL was confirmed by immunofluorescence staining following MMC (5 μM, overnight) or cisplatin (25 μM, 2 hours) treatment in shFBL and shNC cells. Scale bar, 10 μm.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(E) The distribution of YBX1 proteins in the nuclear and cytoplasmic fractions of control or FBL KD HCT116 cells after 5 μM MMC incubation overnight were determined by western blotting assays. H3 was used as a nuclear control. GAPDH was used as a cytoplasmic control.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(F) The protein contents of YBX1 in the nuclear and cytoplasmic fractions in FBL KD HCT116 cells reconstituted with wild-type FBL or deletion mutants of FBL with 5 μM MMC treatment overnight were detected by western blotting assays with indicated antibodies.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(A) A Volcano plot of differentially expressed gene analysis results for RNA-seq data comparing FBL KD HCT116 cells (n = 3) to control cells (n = 3). The dots for significant upregulated or downregulated genes were colored in red or blue, respectively.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "(E) The mRNA and protein levels of BRCA1 and RAD51 were validated by RT-qPCR and western blot assays using FBL KD HCT116 cells or control cells. Ct values were normalized to GAPDH. The bar graphs present data as mean ± SD from three independent experiments. The statistical significance was determined using Student's t-test. ***P < 0.001.",
    "ncbi_link": "BRCA1: 672
FBL: 2091
RAD51: 5888"
  },
  {
    "caption": "(F) The mRNA and protein levels of BRCA1 were validated by RT-qPCR and Western blotting assays using YBX1-silenced HCT116 cells or control cells. Ct values were normalized to GAPDH. The bar graphs present data as mean ± SD from three independent experiments. The statistical significance was determined using Student's t-test. ***P < 0.001.",
    "ncbi_link": "YBX1: 4904"
  },
  {
    "caption": "(C) HE staining of tumor tissues. Scale bar, 50 µm. (D Representative images of immunohistochemical staining showing BRCA1 and γH2AX expression levels in MMC-treated and untreated xenograft tumors driven by control or FBL KD HCT116 cells. panel displays quantification of the (D) panel: showing BRCA1 and γH2AX expression levels. Scale bar, 25 µm. Graphs represent the mean ± SD (n = 3 mice in each group). The statistical significance was determined using one-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001.",
    "ncbi_link": "FBL: 2091"
  },
  {
    "caption": "The rapZ  mutants were expressed from plasmids under control of the PBAD promoter (induction with arabinose, repression by glucose) and tested for the ability to complement a strain lacking the chromosomal rapZ  gene in (b) Northern blotting experiment detecting GlmZ  (top panel) and 5S rRNA (bottom panel; loading control) to assess the degree of GlmZ  cleavage triggered by the RapZ  variants. Processed GlmZ  is indicated with an asterisk. Strains Z8 (wild-type, lanes 1, 2) and Z28 (∆rapZ, all other lanes were used. Strain Z28 carried plasmid pBAD33 (lanes 3, 4; empty vector control = VC) or derivatives triggering synthesis of the indicated RapZ  variants",
    "ncbi_link": "5S rRNA: 
GlmZ: 2847678
rapZ: 947727
RapZ: 947727"
  },
  {
    "caption": "The rapZ  mutants were expressed from plasmids under control of the PBAD promoter (induction with arabinose, repression by glucose) and tested for the ability to complement a strain lacking the chromosomal rapZ  gene in (c) GlmS  protein (MW = 66.9 kDa) levels in the same cultures as revealed by  SDS-PAGE  of total protein extracts followed by Coomassie blue staining. Strains Z8 (wild-type, lanes 1, 2) and Z28 (∆rapZ, all other lanes were used. Strain Z28 carried plasmid pBAD33 (lanes 3, 4; empty vector control = VC) or derivatives triggering synthesis of the indicated RapZ  variants",
    "ncbi_link": "rapZ: 947727
RapZ: 947727"
  },
  {
    "caption": "The rapZ  mutants were expressed from plasmids under control of the PBAD  promoter (induction with arabinose, repression by glucose) and tested for the ability to complement a strain lacking the chromosomal rapZ  gene in (d)  β-Galactosidase activities produced by the same cultures and replicates (mean values and standard deviations are shown). Cells carry a  glmS'-lacZ  fusion on the chromosome, which requires base-pairing with sRNA GlmZ  for high expression. Strains Z8 (wild-type columns 1, 2) and Z28 all other columns) were used. Strain Z28 carried plasmid pBAD33 columns 3, 4; empty vector control = VC) or derivatives triggering synthesis of the indicated RapZ  variants",
    "ncbi_link": "lacZ: 
GlmZ: 2847678
rapZ: 947727
RapZ: 947727"
  },
  {
    "caption": "(H-I) EHD1 depletion prevents CP110 degradation upon serum starvation. (H) Mock-transfected RPE-1 cells or EHD1 siRNA-transfected RPE-1 cells were grown in media containing serum, or serum starved for 4 h in the absence or presence of MG132, and then lysed, separated by SDS-PAGE and immunoblotted with anti-CP110 antibodies (upper panel) or anti-actin antibodies (loading control; lower panel). Validation of EHD1 depletion is shown in the right panel. (I) Graph displaying densitometric analysis of the intensity of the CP110 bands shown in H normalized to actin (means and p-values are representative of 3 independent experiments). Normal distribution was determined by the Shapiro-Wilk normality test.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "(A-B) PCM1-depletion impedes CP110 ubiquitination upon serum starvation. (A) Mock-transfected RPE-1 cells were maintained in media with serum, and both mock-transfected and PCM1 siRNA-transfected cells were serum starved for 4 h in the presence of MG132 prior to lysis and immunoblotting with anti-CP110 antibodies (second panel from top), or first immunoprecipitated with anti-CP110 antibodies and then immunoblotted with antibodies to detect ubiquitinated CP110 (top panel). Bottom panels depict the efficacy of PCM1 depletion upon PCM1 siRNA-transfection, with actin as a loading control. (B) Graph displaying densitometric analysis of ubiquitinated CP110 levels (from the upper panel of A) normalized to total CP110 immunoprecipitated. Normal distribution was determined by the Shapiro-Wilk normality test.",
    "ncbi_link": "PCM1: 5108"
  },
  {
    "caption": "(D-G) Serum starved mock-transfected RPE-1 cells on cover-slips were fixed and immunostained with antibodies directed against acetylated tubulin and CP110 and display primary cilia generation (marked by acetylated tubulin; D, F and inset in G) and removal of CP110 from the m-centriole (E-G; see arrow marking CP110 only on the daughter centriole). (H-K) Serum starved PCM siRNA-transfected RPE-1 cells on cover-slips were fixed and immunostained with antibodies directed against acetylated tubulin and CP110 and display limited ciliogenesis (H, J and inset in K) and failure to remove CP110 from the m-centriole (I-K; see arrows identifying CP110 on both centrioles).",
    "ncbi_link": "PCM: 5108"
  },
  {
    "caption": "EHD1 regulates the distribution of centriolar satellites to the centrosomal region. Mock-transfected RPE-1 cells on cover-slips were serum starved and immunostained with antibodies against acetylated tubulin and PCM1 and EHD1 siRNA-transfected cells on cover-slips were serum starved and immunostained with antibodies against acetylated tubulin and PCM1 The p-values are calculated for all non-ciliated and ciliated mock-transfected cells compared to all EHD1 siRNA non-ciliated and ciliated cells. Note that as expected, among the EHD1-depleted cells, there are minimal cells that display ciliation.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "(A) Validation of siRNA depletion. RPE-1 cells were mock-transfected or transfected with siRNA oligonucleotides to impair translation of Cullin3, HERC2, or MIB1. 72 h later, the cells were lysed, subjected to SDS-PAGE and immunoblotted. Immunoblotting with anti-actin antibodies was done as a loading control.",
    "ncbi_link": "Cullin3: 8452
HERC2: 8924
MIB1: 57534"
  },
  {
    "caption": "(B) HERC2 or MIB1 depletion impairs CP110 ubiquitination. RPE-1 cells were grown in serum (first lane from left), or with MG132 in the absence of serum for 4 h (second lane from left), transfected with Cullin3 siRNA-oligonucleotides and treated with MG132 in the absence of serum for 4 h (third lane from left), transfected with HERC2 siRNA-oligonucleotides and treated with MG132 in the absence of serum for 4 h (fourth lane from left), or transfected with MIB1 siRNA-oligonucleotides and treated with MG132 in the absence of serum for 4 h (fifth lane from left). Cells were lysed and immunoprecipitated with anti-CP110 antibodies, and the resultant immunoprecipitates were immunoblotted with anti-ubiquitin to identify ubiquitinated CP110 (upper panel). The blot was then stripped and re-immunoblotted with anti-CP110 to reveal the amount of CP110 pulled-down from the lysate (lower panel).",
    "ncbi_link": "Cullin3: 8452
HERC2: 8924
MIB1: 57534"
  },
  {
    "caption": "(B-M) (B-D) Mock-transfected cells, (E-G) MIB1 siRNA-transfected cells, (H-J) HERC2 siRNA-transfected cells, or (K-M) MIB1 and HERC2 siRNA-transfected cells on cover-slips were fixed and immunostained with antibodies against acetylated tubulin (insets; C, F, I, L: merged field; B, E, H, K) and CP110 (insets; D, G, J, M: merged field; B, E, H, K). Bars (B, E, H, K), 10 mm. Bars (C, D, F, G, I, J, L, M), 2 μm.",
    "ncbi_link": "HERC2: 8924
MIB1: 57534"
  },
  {
    "caption": "(A) EHD1 is required for the interaction between HERC2 and CP110. RPE-1 cells were mock-transfected or transfected with EHD1 siRNA oligonucleotides for 72 h. Cells were lysed and immunoprecipitated with anti-CP110 or beads only (control) and separated by SDS-PAGE along with 7% of the lysate (input). After transfer to nitrocellulose, antibodies were used to detect CP110 (lower panel) and HERC2 (upper panel).",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "(G-H) Representative micrographs of RPE-1 cells on cover-slips that were mock-transfected (G) or EHD1 siRNA-transfected (H) and immunostained with antibodies to acetylated tubulin (red) or HERC2 (green). Dashed yellow regions of interest highlight the centrosomal area. Arrows denote the HERC2 signal observed in each micrograph. Bars, 1 μm.",
    "ncbi_link": "EHD1: 10938"
  },
  {
    "caption": "(A-D) RPE-1 cells on coverslips were mock-transfected (A), transfected with CP110 siRNA-oligonucleotides (B) transfected with HERC2 siRNA-oligonucleotides (C), or transfected with both CP110 and HERC2 siRNA-oligonucleotides (D). Cells were fixed and immunostained with acetylated tubulin to detect primary cilia (yellow arrows). Bars, 10 μm. : Graphs show standard deviation and p-values from 3 independent experiments. The micrographs (A-D) are representative ones from the 3 individual biological experiments. More than 50 cells were quantified in each experiment, although fewer ciliated cells were observed and measured under the HERC2 knock-down condition.",
    "ncbi_link": "CP110: 9738
HERC2: 8924"
  },
  {
    "caption": "(E) Immunoblot demonstrating the efficacy of depletion for CP110 (middle panel), HERC2 (top panel), and simultaneous CP110 and HERC2 depletion (middle and top panels). Actin was used as a loading control (bottom panel). : Graphs show standard deviation and p-values from 3 independent experiments. immunoblots (E) are representative ones from the 3 individual biological experiments.",
    "ncbi_link": "CP110: 9738
HERC2: 8924"
  },
  {
    "caption": "A Levels of VEGF-A mRNA in the intestinal tissues from  COVID-19 patients (n=5) or healthy controls (n=5) by RNA-seq. Data information: All data are shown as mean ± SD. For (A), P values are determined by Student's t-test",
    "ncbi_link": "VEGF-A: 7422"
  },
  {
    "caption": "A qRT-PCR analysis of levels of VEGF mRNA in HUVEC treated with Control-Fc or Spike RBD-Fc. For each group, n=3. Data are from 3 independent biological experiments. Data information: All data are shown as mean ± SD. For (A) P values are determined by Paired Student's t-test",
    "ncbi_link": "VEGF: 7422"
  },
  {
    "caption": "Representative grey-scale images of primary rat hippocampal neurons (DIV 10) transfected with GFP and the indicated miRNA mimics. Quantification of the mean number of intersections by Sholl analysis. GFP-only transfected conditions were set to one in each experiment.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Representative grey-scale images of GFP-transfected Cacna1c+/+ (WT) or Cacna1c+/- primary rat hippocampal neurons (DIV 10). Scale bars = 50 μm.   Quantification of the mean number of intersections by Sholl analysis. Data are represented as scattered dot plots with bar, mean±S.D. (n=3 independent experiments; Unpaired two-sample t-Test, **p=0.0096). Fold changes represent changes in dendritic complexity relative to the control condition.  ",
    "ncbi_link": "GFP: 
Cacna1c: 24239"
  },
  {
    "caption": "Representative images of DIV 10 hippocampal neurons co-transfected with control or miR-499-5p mimics and a pMT2-CACNB2 expression plasmid (CACNB2). Scale bars = 50 μm.   Quantification of the mean number of intersections by Sholl analysis. Data are represented as scattered dot plots with bar, mean±S.D. (n=3 independent experiments; Two-way ANOVA: no main effect of the CACNB2 transfection p=0.5027 or the miRNA mimics p=0.0805, main effect of the CACBN2 transfection by miRNA mimics interaction p=0.0213, Tukey's HSD: *p=0.0303). Fold changes represent the changes in dendritic complexity of transfected neurons compared to non-treated control neurons. ns = not significant.  ",
    "ncbi_link": "CACBN2: 116600
CACNB2: 116600
miR-499-5p: 100314091"
  },
  {
    "caption": "A) Representative images of DIV 19 rat hippocampal neurons co-transfected with GFP (green channel) and Cav1.2-HA (red channel), together with either control or miR-499-5p mimics. After 12-13 days of expression, labeling with Anti-HA antibodies was performed in live conditions to identify cell surface Cav1.2 channels. Whole cells: scale bars = 20 μm; cell body and dendrite insets: scale bars= 5 μm. B) Quantification of the area occupied by surface Cav1.2 fluorescence normalized to the total cell area (GFP fluorescence) from non-permeabilized neurons transfected as in A). Data are represented as scattered dot plots with bar, mean±S.D. (n=4 independent experiments; Paired two-sample t-Test *p=0.0318).",
    "ncbi_link": "GFP: 
HA: 
Cav1.2: 24239
miR-499-5p: 100314091"
  },
  {
    "caption": "D) Representative Western blot images of CACNB2 (upper panel) and GAPDH (lower panel) protein expression levels in the hippocampus of WT rats and Cacna1c +/- rats injected with the AAV-Control or AAV-miR-499 hairpin viruses. GAPDH was used as a loading control E) Quantification of CACNB2 Western blots using hippocampal protein lysate from wild type rats injected with either AAV-control or AAV-miR-499. Data are represented as box plot with whiskers and data points (+: mean, line: median; whiskers: minimum and maximum values). (*p=0.0103, Unpaired two-sample t-Test; n=7 rats in the AAV-Control group, n=6 rats in the AAV-miR-499 group). F) Quantification of CACNB2 Western blots using hippocampal protein lysate from Cacna1c +/- rats injected with either AAV-control or AAV-miR-499. Data are represented as box plot with whiskers and data points (+: mean, line: median; whiskers: minimum and maximum values). (**p=0.0044, Unpaired two-sample t-Test; n=8 rats in the AAV-Control group, n=7 rats in the AAV-miR-499 group).",
    "ncbi_link": "Cacna1c: 24239
miR-499: 100314091"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 26, male= 31), BD (female= 26, male= 37), or MDD (female= 18, male=24) subjects. Wilcoxon rank sum test after correction for age and antidepressant treatment (linear model of the form Fold Change ~ Group*Sex + Age + Antidepressant treatment). 2-way ANOVA with correction for sex, age and antidepressant treatment (linear model of the form Fold Change ~ Group*Sex + Age + Antidepressant treatment). Control vs. BD: ****p=8.89e-07; control vs. MDD: n.s. p=0.12674. Data are presented as violin plots with median, quartiles and data points.",
    "ncbi_link": "miR-499-5p: 574501"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 8, male= 10) and SZ (female= 8, male= 15) subjects. 2-way ANOVA, Main effect Sex: p=0.9785; main effect Group: p= 0.0924; main effect Interaction: p= 0.9802. Tukey's HSD: p=0.0924, ns. Data are presented as violin plots with median, quartiles and data points.",
    "ncbi_link": "miR-499-5p: 574501"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control (female= 26, male= 31), BD I (female= 9, male= 9), or BDI II (female= 12, male=16) subjects. 2-way ANOVA, Main effect Sex: p=0.174; main effect Group: ****p=4.07e-09; Interaction Group x Sex: p=0.311. Tukey's HSD: control vs. BDI: ****p=0.0000037. control vs. BDII:p=0.0000002. Data are presented as violin plots with median, quartiles and data points.",
    "ncbi_link": "miR-499-5p: 574501"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of control subjects (female= 26, male= 31), and BD subjects in different mood states (depressive (female= 7, male=11), euthymic (female= 7, male=4), hypomanic (female=2, male=6), manic (female=2, male=1), mixed (female=1, male=1). 2-way ANOVA, main effect Sex: p=0.260; main effect Group: p=1.26e-07; Interaction Group x Sex: p=0.059; Tukey's HSD: control vs. depressive ***p=0.0002621, control vs. euthymic ***p=0.0008533, control vs. hypomanic ****p=0.0000470. Data are presented as violin plots with median, quartiles and data points.",
    "ncbi_link": "miR-499-5p: 574501"
  },
  {
    "caption": "miR-499-5p qPCR analysis of total RNA isolated from PBMCs of healthy control subjects (-CMT, n=17) and healthy subjects with a history of childhood maltreatment (+CMT, n=17). (****p<0.0001, Mann-Whitney U test). CMT: Childhood maltreatment. Data are presented as violin plots with median, quartiles and data points.",
    "ncbi_link": "miR-499-5p: 574501"
  },
  {
    "caption": "Association of miR-499-5p expression and GMV in HC (n=23): miR-499-5p levels were negatively correlated with a GMV cluster comprising parts of the left Wernicke language area (i.e. transverse temporal gyrus, the left parietal operculum and the left superior temporal gyrus) (in blue) at p<.05 cluster-level family wise error-corrected (FWE) for multiple comparisons after an initial threshold of p<.001 uncorrected (k=1090, x/y/z=-42/-30/15, t= 4.7, p=.045).",
    "ncbi_link": "miR-499-5p: 100314091"
  },
  {
    "caption": "(A) p53-dependent dephosphorylation of Ulk1 at Ser637. p53+/+ and p53−/−MEFs were treated with etoposide (10 µM), and the expression of each protein was examined by western blotting. Dead cells (%) indicates the population of apoptotic cells assessed by propidium iodide (PI) staining. α-Tubulin was used as a loading control. A semiquantitative analysis of protein expression is shown in Fig. EV1.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(B, C) PPM1D-dependent dephosphorylation of Ulk1 at Ser637 and the induction of autophagy. PPM1D+/+MEFs and PPM1D−/−MEFs were treated with etoposide (10 µM), and the expression of each protein was examined by western blotting. Dead cells (%) indicates the population of apoptotic cells.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B, C) PPM1D-dependent dephosphorylation of Ulk1 at Ser637 and the induction of autophagy. PPM1D+/+MEFs and PPM1D−/−MEFs were treated with etoposide (10 µM), and the expression of each protein was examined by western blotting. Dead cells (%) indicates the population of apoptotic cells. (C) Semiquantitative analysis of protein expression is shown (n = 3; mean ± SD). *p < 0.05, **p < 0.01, NS: not significant. (D-I) Suppression of etoposide-induced autophagy in PPM1D−/−MEFs.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(D, E) The indicated MEFs were treated with etoposide (10 µM) for 6 hr and then immunostained with an anti-LC3 antibody (green). Representative images are shown in (D). LC3 puncta are observed in etoposide-treated PPM1D+/+MEFs. (E) The proportion of cells with LC3 puncta was calculated (n > 100 cells in each experiment). Data are shown as the mean  ±  SD (n = 3 experiments). *p < 0.05, **p < 0.01.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(F, G) The indicated MEFs were treated with etoposide (10 µM) for 6 hr and then analyzed using electron microscopy. Representative images are shown in (F). Many autophagic vacuoles (arrows) can be seen in etoposide-treated PPM1D+/+cells (upper panel). \"N\" indicates the nucleus. Bar = 2 µm. A representative autophagosome (AP) and autolysosome (AL) are shown in the insets. (G) The number of autophagosomes and autolysosomes in each cell were counted (n > 8 cells). Red lines indicate the mean value. *p < 0.05.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(A, B) Effect of stable expression of PPM1D in PPM1D−/−MEFs. PPM1D−/−MEFs and PPM1D-transfected PPM1D−/−MEFs were treated with etoposide (10 µM), and the expression of each protein was examined by western blotting. (B) Semiquantitative analyses of protein expression in (A) (n = 3; mean ±  SD). *p < 0.05, **p < 0.01, NS: not significant.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(E, F) Effect of the transient overexpression of PPM1D. PPM1D+/+MEFs were transfected with a PPM1D-Flag plasmid in the presence or absence of bafilomycin A1 (10 nM), and the expression of each protein was examined by western blotting. (F) Semiquantitative analyses of protein expression in (E) (n = 3; mean  ±  SD). *p < 0.05, **p < 0.01, NS: not significant.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B) Interaction between endogenous Ulk1 and recombinant PPM1D. Lysates from healthy PPM1D+/+ MEFs were incubated with GST-PPM1D or GST. Binding molecules were then analyzed by western blotting using anti-Ulk1 and anti-GST antibodies. \"Total lysate\" indicates 7% of the lysates that were incubated with GST fusion protein.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(C) In vitro Ulk1 dephosphorylation assay. Immunoprecipitated Ulk1 from PPM1D+/+ MEF lysates was incubated with GST-PPM1D (1 µg) with or without a phosphatase inhibitor cocktail for 1 hr. Then, the extent of Ulk1 dephosphorylation was analyzed by western blotting using anti-phospho-Ulk1637 and anti-phospho-Ulk1757 antibodies. Semiquantitative analyses are shown in Fig. EV2B.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(F-J) The crucial role of Ulk1 dephosphorylation at Ser637 in etoposide-induced autophagy. (F-H) Ulk1/Ulk2 DKO MEFs that were stably transfected with HA-Ulk1 or its mutants, S637D and S637A, were treated with etoposide (10 µM). Then, the cell lysates were collected time-dependently, and the expression of each protein was examined by western blotting. Asterisks in the Ulk1 blots are nonspecific bands. Semiquantitative analyses are shown in Fig. EV2E.",
    "ncbi_link": "Ulk1: 22241
Ulk2: 29869"
  },
  {
    "caption": "(F-J) The crucial role of Ulk1 dephosphorylation at Ser637 in etoposide-induced autophagy. (I, J) The indicated MEFs were treated with or without etoposide (10 µM) for 6 hr, followed by immunostaining with an anti-LC3 antibody. Representative images are shown in (I). LC3 puncta are markedly observed in DKO MEFs transfected with wild-type HA-Ulk1. Puncta were absent and weakly observed in MEFs expressing the mutants S637D and S637A, respectively. (J) The population of cells with LC3 puncta was calculated (n > 100 cells in each experiment). Data are shown as the mean  ±  SD (n = 3 experiments). *p < 0.05, **p < 0.01.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(A-D) Ulk1 puncta formation was induced by etoposide in a PPM1D-dependent manner. The indicated MEFs were treated with etoposide (10 µM) with or without GSK2830371 (20 µM) for the indicated times, followed by immunostaining with an anti-Ulk1 antibody. Representative images are shown in (A). Ulk1 puncta are observed in etoposide-treated PPM1D+/+MEFs. (B-D) The proportion of cells with Ulk1 puncta was calculated (n > 100 cells in each experiment). Data are shown as the mean  ± SD (n = 3 experiments). *p < 0.05, **p < 0.01, NS: not significant.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(E-I) Role of the dephosphorylation of Ulk1 at Ser637 on etoposide-induced Ulk1 puncta formation and Atg13 phosphorylation. Ulk1/Ulk2 DKO MEFs stably transfected with HA-Ulk1 or its mutants, S637D and S637A, were treated with etoposide (10 µM) for the indicated times. (E, F) Cells were immunostained with an anti-Ulk1 antibody (E), and the population of cells with Ulk1 puncta was calculated (n > 100 cells in each experiment) (F). Data are shown as the mean  ±  SD (n = 3 experiments). *p < 0.05, **p < 0.01.",
    "ncbi_link": "Ulk1: 22241
Ulk2: 29869"
  },
  {
    "caption": "(E-I) Role of the dephosphorylation of Ulk1 at Ser637 on etoposide-induced Ulk1 puncta formation and Atg13 phosphorylation. Ulk1/Ulk2 DKO MEFs stably transfected with HA-Ulk1 or its mutants, S637D and S637A, were treated with etoposide (10 µM) for the indicated times. (G-I) Cell lysates were collected in a time-dependent manner, and Atg13 protein levels and its phosphorylation at Ser317 were examined by western blotting. Semiquantitative analyses are shown in Fig. EV3D.",
    "ncbi_link": "Ulk1: 22241
Ulk2: 29869"
  },
  {
    "caption": "(J) EGFP-DFCP1-expressing PPM1D+/+MEFs were treated with etoposide (10 µM) for the indicated times, followed by immunostaining with an anti-Ulk1 antibody. Representative images of EGFP-DFCP1 (green; left), anti-Ulk1 (red; center), and a merged image (right) are shown. The nuclei were stained with Hoechst 33342 in the merged image. A magnified image of the area within the dashed square is also shown. Arrowheads indicate DFCP1 puncta localized close to Ulk1 puncta.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(K, L) The role of Ulk1 dephosphorylation at Ser637 on etoposide-induced DFCP1 puncta formation. Ulk1/Ulk2 DKO MEFs stably transfected with HA-Ulk1 or its mutants, S637D and S637A, were transfected with EGFP-DFCP1 and treated with etoposide (10 µM) for the indicated hours, followed by immunostaining with an anti-HA antibody. Representative merged images of EGFP-DFCP1 (green), anti-HA (red), and Hoechst 33342 (blue) are shown in (K). Arrowheads indicate DFCP1 puncta localized close to Ulk1 puncta. The number of DFCP1 puncta in each cell was calculated and is shown in (L) (n > 8 cells in each experiment). Red lines indicate the mean values. **p < 0.01, NS: not significant.",
    "ncbi_link": "Ulk1: 22241
Ulk2: 29869"
  },
  {
    "caption": "(A) PPM1D-dependent dephosphorylation of Ulk1 at Ser637, induction of autophagy, and degradation of Noxa. PPM1D+/+ and PPM1D−/− primary thymocytes were X-rayirradiated (5 Gy), and 3 hr later, thymocytes were lysed and the expression of each protein was examined by western blotting. α-Tubulin was used as a loading control. Semiquantitative analyses are shown in Fig. EV5B.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B-F) Suppression of X-ray-induced autophagy in PPM1D−/−thymocytes. (B, C) The indicated thymocytes were X-rayirradiated (5 Gy), and 3 hr later, thymocytes were immunostained with an anti-LC3 antibody. Nuclei were stained with Hoechst 33342. Representative images are shown in (B). LC3 puncta can be seen in irradiatedPPM1D+/+thymocytes (arrowheads). In (C), the proportion of cells with LC3 puncta was calculated (n > 100 cells in each experiment). Data are shown as the mean  ± SD (n = 3 experiments). *p < 0.05.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B-F) Suppression of X-ray-induced autophagy in PPM1D−/−thymocytes. (D) The indicated thymocytes were X-ray irradiated (5 Gy), and 3 hr later, thymocytes were subjected to EM analysis. An autophagic vacuole (arrowhead) can be seen in an irradiated PPM1D+/+thymocyte.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B-F) Suppression of X-ray-induced autophagy in PPM1D−/−thymocytes. (E) The indicated thymocytes were X-ray irradiated (5 Gy), and 3 hr later, thymocytes were stained with Cyto-IDTM. Representative flow cytometry data are shown. Quantitative data are shown in Fig. EV5C. Cyto-ID fluorescence in irradiated PPM1D+/+thymocytes was higher than that in the other thymocytes.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(B-F) Suppression of X-ray-induced autophagy in PPM1D−/−thymocytes. (F) Analysis of autophagic flux. The indicated thymocytes were X-rayirradiated (5 Gy) in the presence or absence of chloroquine (120 µM), and the expression of each protein was examined by western blotting. α-Tubulin was included as a loading control. Semiquantitative analyses are shown in Figure EV4D.",
    "ncbi_link": "PPM1D: 53892"
  },
  {
    "caption": "(G-J) Contribution of PPM1D/Ulk1-dependent autophagy to irradiation-induced apoptosis. (G) Thymocytes were X-ray irradiated (5 Gy), and 6 hr later, cell death was determined using the PI assay. Data represent the mean  ± SD (n = 3 independent thymi). *p < 0.05, **p < 0.01, NS: not significant.",
    "ncbi_link": "PPM1D: 53892
Ulk1: 22241"
  },
  {
    "caption": "(G-J) Contribution of PPM1D/Ulk1-dependent autophagy to irradiation-induced apoptosis. (H, I) Thymocytes were X-rayirradiated (5 Gy), and 3 hr later, the expression of each protein was examined by western blotting. α-Tubulin was included as a loading control. (I) Semiquantitative analyses are shown (n = 3; mean  ±  SD). *p < 0.05, **p < 0.01.",
    "ncbi_link": "PPM1D: 53892
Ulk1: 22241"
  },
  {
    "caption": "(G-J) Contribution of PPM1D/Ulk1-dependent autophagy to irradiation-induced apoptosis. (J) Indicated thymocytes were X-ray irradiated (5 Gy), and 3 hr later, caspase3/7 activity was examined using the Caspase-Glo 3/7 assay (Promega) according to the manufacturer's protocol. Data are shown as the mean  ± SD (n = 3 experiments). *p < 0.05, **p < 0.01.",
    "ncbi_link": "PPM1D: 53892
Ulk1: 22241"
  },
  {
    "caption": "(K) The effect of Noxa siRNA on thymocytes. The indicated thymocytes were transfected with the pmaxGFP vector and siRNAs. After 12 hr, cells were X-ray irradiated (5 Gy), and 6 hr or 10 hr later, the population of dead cells among the GFP-positive cells was determined using the PI assay. Data are shown as the mean  ± SD (n = 3 experiments). *p < 0.05, NS: not significant.",
    "ncbi_link": "Noxa: 58801"
  },
  {
    "caption": "A. Up: The schematic diagram of PGCs induced from  chicken ESCs in vitro. Down: Morphological observation of the number of  embryoid bodies  in the in vitro PGCs induction model after LncBMP4overexpression and interference; oeLncBMP4 indicates the overexpression of LncBMP4; shLncBMP4 indicates the interference of LncBMP4; BMP4 induction was regarded as the control. Scale bar: 60 µm (n = 3 independent experiments).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "B. The expression  of reproductive marker genes (Cvh  and C-kit), LncBMP4, and BMP4 were detected by  qRT-PCR after LncBMP4 overexpression and interference, in vitro (Data are shown as mean ± SEM, n = 3 independent experiments, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, one-way ANOVA) .",
    "ncbi_link": "BMP4: 396165
Cvh: 395447
C-kit: 378783"
  },
  {
    "caption": "A. The results of IHC examining using anti-DDX4 antibody shows that the overexpression of LncBMP4 increases the  number  of PGCs in the genital ridge, and interference with LncBMP4 reduces the number of PGCs in the genital ridge. The number  of PGCs was counted through the Segmentation module of Image J software. Scale bars:200 μm (top row),40 μm (bottom row) (Data are shown as mean ± SEM, n = 3 independent experiments, * p < 0.05, ** p < 0.01, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "B. The number of PGCs in the  genital ridge, following the overexpression or interference of LncBMP4, as determined by flow cytometry (Data are shown as mean ± SEM, n = 3 independent experiments, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "D. The expression  of reproductive marker genes (Cvh and C-kit), LncBMP4, and BMP4 were detected by qRT-PCR in the  genital ridge after gga-mir-12211  overexpression and interference in vitro (Data are shown as mean ± SEM, n =3 independent experiments, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165
Cvh: 395447
C-kit: 378783
mir-12211: 114483374"
  },
  {
    "caption": "A. A luciferase  reporting system was used to detect the regulatory effects of gga-mir-12211 on the activity of  BMP4-3'UTR (Data are shown as mean ± SEM, n =3 independent experiments, * p < 0.05, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "luciferase: 
BMP4: 396165
mir-12211: 114483374"
  },
  {
    "caption": "B.  qRT-PCR was used to detect the regulatory effects of gga-mir-12211  on LncBMP4 expression (Data are shown as mean ± SEM, n =3 independent experiments, *** p < 0.001, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165
mir-12211: 114483374"
  },
  {
    "caption": "Enrichment levels of  m6A in LncBMP4 were detected by RIP-qPCR (Data are shown as mean ± SEM, n =3 independent experiments, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "H and I. The effects of m6A modifications of LncBMP4 on the ceRNA system were detected by the luciferase reporting system (Data are shown as mean ± SEM, n =3 independent experiments, * p < 0.05, **** p < 0.0001, one-way ANOVA.).",
    "ncbi_link": "luciferase: 
BMP4: 396165"
  },
  {
    "caption": "A. The influence of  m6A on the stability of LncBMP4 was detected by qRT-PCR (Data are shown as mean ± SEM, n =3 independent experiments, **** p < 0.0001, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "D. The enrichment level of m6A, for LncBMP4 variants with the progressive accumulation of RRACH site mutations, was detected by RIP-qPCR   (Data are shown as mean ± SEM, n =3 independent experiments, * p < 0.05, ** p < 0.01, one-way ANOVA).",
    "ncbi_link": "BMP4: 396165"
  },
  {
    "caption": "E. The ability of LncBMP4, modified with different levels of  m6A, to bind gga-mir-12211 was detected by the  luciferase  reporting system (Data are shown as mean ± SEM, n =3 independent experiments, ** p < 0.01, **** p < 0.0001, one-way ANOVA.).",
    "ncbi_link": "luciferase: 
BMP4: 396165
mir-12211: 114483374"
  },
  {
    "caption": "D and E. Western blot(Up) was used to detect gga-mir-12211 and  m6A affect the ability of LncBMP4  to translate EPC5. Image J software was used for  gray level analysis(Down) (Data are shown as mean ± SEM, n =3 independent experiments, *** p < 0.001,**** p < 0.0001, one-way ANOVA.).",
    "ncbi_link": "BMP4: 396165
mir-12211: 114483374"
  },
  {
    "caption": "(G) Kaplan-Meier survival plots. Differences between the control group (WT) and the FKN group were evaluated by a two-sided log-rank test.",
    "ncbi_link": "FKN: 20312"
  },
  {
    "caption": "(C) Kaplan-Meier survival plots of the indicated groups of mice. Survival differences between the control group (WT + αPD-1) and FKN + αPD-1 were evaluated by a two-sided log-rank test.",
    "ncbi_link": "FKN: 20312"
  },
  {
    "caption": "(D) Kaplan-Meier survival plot of the indicated treatment groups. Survival differences between the control group (WT) and FKN were evaluated by two-sided log-rank test.",
    "ncbi_link": "FKN: 20312"
  },
  {
    "caption": "(G&H) WT or TRIM21 KO L929  cells were infected with MHV-A59 in the presence of electroporated  polyclonal antiserum (G) or anti-N antibody (H) and quantified by  cell area 48h later. Co-electroporation of Protein  A/G with anti-N antibody into WT cells mimics the TRIM21  KO phenotype. Data information: Data was analysed using a Students t-test. Error bars depict the mean +/- SEM. All data represents at least two independent replicates.",
    "ncbi_link": "TRIM21: 20821"
  },
  {
    "caption": "(A&B)  Vero  cells OE ACE2  and TMPRSS2  were infected with SARS-CoV-2 in the presence of IgG or anti-N antibodies added directly into media or electroporated  into cells. Viral replication was then determined by RT-qPCR  (A) or plaque assay (B). Electroporation of anti-N antibodies significantly inhibits SARS-CoV-2 replication (*** = p < 0.0002). Data information: All data represents at least three independent replicates. Error bars depict the mean +/- SEM. Statistical comparisons were performed using a one-way ANOVA.",
    "ncbi_link": "ACE2: 103231639
TMPRSS2: 103219191"
  },
  {
    "caption": "(F&G) 293T ACE2 OE/TRIM21  KO cells reconstituted with EV or TRIM21, electroporated  with IgG or anti-N antibodies, and infected with SARS-CoV-2. Viral replication was then determined by RT-qPCR (F) or plaque assay (G). Electroporation of anti-N antibodies significantly inhibits SARS-CoV-2 replication only in  TRIM21-reconstituted cells (* = p < 0.05). Data information: All data represents at least three independent replicates. Error bars depict the mean +/- SEM. Statistical comparisons were performed using two-way ANOVA.",
    "ncbi_link": "ACE2: 59272
TRIM21: 6737"
  },
  {
    "caption": "(C)  293T  cells OE ACE2 infected with SARS-CoV-2  in the presence of  electroporated  convalescent  sera. There are statistically significant differences in the ability of serum from different individuals to inhibit viral replication intracellularly (** = p< 0.005, * = p< 0.05). (D) 293T ACE2 OE/TRIM21 KOs reconstituted with either empty vector (EV) or TRIM21-expressing vector (TRIM21) infected with SARS-CoV-2 in the presence of electroporated convalescent  sera. Intracellular neutralization of viral replication is only observed in cells reconstituted with TRIM21 (** = p< 0.005). Data information: All data represents at least three independent replicates. Error bars depict the mean +/- SEM. Statistical comparisons were performed using a one-way (C) or two-way (D) ANOVA.",
    "ncbi_link": "ACE2: 59272
TRIM21: 6737"
  },
  {
    "caption": "Immunoblot analysis of p-SMAD2 and total SMAD2 (t-SMAD2) in NMuMG cells with or without Ugcg deficiency and treated with vehicle control or TGF-β for 1 h. Tubulin: loading control.",
    "ncbi_link": "Ugcg: 22234"
  },
  {
    "caption": "Immunoblot analysis of E-cadherin and N-cadherin in Ugcg KO NMuMG or control NMuMG cells treated with vehicle control or TGF-β for 48 h. Tubulin: loading control.",
    "ncbi_link": "Ugcg: 22234"
  },
  {
    "caption": "Lysates from NMuMG control cells (Cas9-expressing cells) and Ugcg KO cells were subjected to sucrose density gradient ultracentrifugation. The expression levels of flotillin-1, β1-integrin, EEA1, and TβRI in the sucrose gradient fractions were analyzed by immunoblotting. Fractions 3, 4, and 5 contained lipid rafts, whereas fractions 10-12 corresponded to the non-lipid raft fractions. Quantification of TβRI percentages in lipid raft and non-lipid raft fractions from Ugcg KO NMuMG and control cells. Isolation of lipid rafts from other cellular components in A549-VIM-RFP cells treated with the UGCG inhibitor eliglustat (2 μM) for 6 days using sucrose density gradient ultracentrifugation and measurement of flotillin-1, β1-integrin, EEA1, and TβRI levels in the sucrose gradient fractions using immunoblot analysis. Fractions 3-6 contained lipid rafts, whereas fractions 10-12 corresponded to the non-lipid raft fractions. Quantification of TβRI percentages in lipid raft and non-lipid raft fractions from A549-VIM-RFP cells treated with eliglustat (2 μM) for 6 days.",
    "ncbi_link": "Cas9: 69900935
Ugcg: 22234"
  },
  {
    "caption": "Ubiquitination of TβRI was detected by immunoprecipitation (IP) of Myc-tagged caTβRI from HA-Ub-transfected HEK293T cells with or without eliglustat (2 μM) treatment for 6 days. All groups were treated with MG132 (5 μM) for 6 h.",
    "ncbi_link": "HA: 
Myc: 
Ub: 
TβRI: 7046"
  },
  {
    "caption": "Immunoblot analysis of p-SMAD2, t-SMAD2, and ST3GAL5 in A549-VIM-RFP cells with siRNA-mediated ST3GAL5 knockdown or transfection of nontargeting siRNA and treated with vehicle control or TGF-β for 1 h. Vinculin: loading control.   Quantification of the p-SMAD2 level in A549-VIM-RFP cells transfected with nontargeting or ST3GAL5 siRNA and treated with TGF-β as shown in (B).  ",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "Expression levels of ST3GAL5, the epithelial marker E-cadherin, and mesenchymal markers, including N-cadherin, vimentin, and SNAIL, in siRNA ST3GAL5-depleted and nontargeting siRNA-transfected A549-VIM-RFP cells treated with vehicle control or TGF-β for 48 h. Vinculin: loading control.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "Immunoblot analysis of p-SMAD2 and t-SMAD2 in A549-VIM-RFP cells transduced with empty vector (pLV-EV) or the ST3GAL5 expression construct and stimulated with vehicle control or TGF-β for 1 h. GAPDH: loading control. Quantification of the p-SMAD2 level in A549-VIM-RFP cells transduced with pLV-EV or the ST3GAL5 overexpression construct and treated with TGF-β, as shown in (F).",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "Immunoblot analysis of the epithelial marker E-cadherin and mesenchymal markers, including N-cadherin, vimentin, and SNAIL, in A549-VIM-RFP cells transduced with the pLV-EV control or ST3GAL5 expression construct and treated with vehicle control or TGF-β for 48 h. GAPDH: loading control.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "HEK293T cells transfected with Myc-tagged caTβRI, (HA-Ub, and nontargeting siRNA or ST3GAL5 siRNA were collected for IP with an anti-Myc antibody and immunoblot analysis. All groups were treated with MG132 (5 μM) for 6 h.",
    "ncbi_link": "HA: 
Myc: 
Ub: 
ST3GAL5: 8869
TβRI: 7046"
  },
  {
    "caption": "Ubiquitination of TβRI was detected by IP of Myc-tagged caTβRI from HA-Ub-transfected HEK293T cells with or without ST3GAL5 overexpression. All groups were treated with MG132 (5 μM) for 6 h.",
    "ncbi_link": "HA: 
Myc: 
Ub: 
ST3GAL5: 8869
TβRI: 7046"
  },
  {
    "caption": "Western blot analysis of TβRI expression in A549-VIM-RFP cells transduced with the pLV-EV control or ST3GAL5 expression construct and treated with CHX for the indicated times. Vinculin: loading control.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "Quantification of TβRI expression in pLV-EV control- and ST3GAL5-expressing A549-VIM-RFP cells. The results were normalized to the t=0 controls.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "In vivo zebrafish extravasation experiments with mCherry-labeled A549 cells with or without ectopic expression of ST3GAL5. Representative images with magnified regions (outlined with dotted squares) of extravasated cells were acquired 4 days after injection by confocal microscopy. The number of extravasated cell clusters was quantified in 30 embryos injected with A549 cells transduced with the pLV-EV control or ST3GAL5 expression construct.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "Box plots of ST3GAL5 gene expression levels in lung cancer tissues and normal tissues in the Bhattacharjee Lung database. The central bands indicate the medium expression values of ST3GAL5, boxes indicate the expression level ranges of ST3GAL5. Data are presented as the means ± SDs from the indicated number of tissues.",
    "ncbi_link": "ST3GAL5: 8869"
  },
  {
    "caption": "D-F, Upper panels, examples for IHCs, co-labelled for otoferlin (magenta) and Vglut3 (green) and position of the line for line scans; maximum projection of few optical sections, scale bars 5µm. Lower panels, for quantification of membrane staining, the fluorescence was normalized to the cellular fluorescence for each fluorophore, then the average of five parallel line scans through the middle of the cells for the sum of both fluorescence values (black line) was used to determine the position of the basal membrane. At the most basal cellular point along this line which exceeds the threshold value of 2 (yellow diamond), the otoferlin-Vglut3 fluorescence difference (blue line) gave the value for relative otoferlinplasma membrane levels (orange diamond). Insets: enlargements of basal regions.G, Otoferlin protein levels were reduced in OtofI515T/I515T IHCs (indicates numbers represent numbers of cells) and OtofPga/Pga IHCs compared to wild-type (Otof+/+) controls (mean±SEM).H, ratio of apical/basal protein levels (above/below nuclear midline depicted as green line in A) indicates an apical shift of otoferlin in OtofPga/Pga IHCs.I, Relative levels of membrane-bound otoferlin at the basal pole of IHCs.K, Absolute amount of otoferlin at the basal IHCplasma membrane, gained by multiplication of relative plasma membrane levels (I) x total cellular otoferlin protein levels (G). Kruskal-Wallis test; *** indicates p<0.001; **, p<0.01; *, p<0.05.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A, ABR thresholds in OtofI515T/I515T (red, n=5) and Otof-/I515T (blue, n=7) mice were elevated compared to Otof+/+ mice (black, n=5) at an age of 3-4 weeks. The grey dotted line indicates the maximum loudspeaker output of 90dB; thresholds exceeding this value were set to 100dB for calculation of the mean ± SEM. At 12kHz, only the threshold increase for Otof-/I515T vs Otof+/+ is significant (Kruskal-Wallis test with Dunn's multiple comparisons test between all 3 groups).B, Grand averages of ABR waveforms ± SEM in response to 80dB click stimulation of the mice analyzed in A: The small wave preceding ABR wave I probably represents the summating potential (SP, hair cell receptor potential), which is intact in Otof mutants. ABR wave I is reduced in amplitude while subsequent peaks are better preserved in OtofI515T/I515T mice (Fig EV1).C, Mean ABR wave I amplitude ± SEM for different stimulus intensities (all differences between genotypes are significant; 2-way ANOVA with Tukey's multiple comparison test).D, At 8 weeks (circles) and 25 weeks (open squares), OtofI515T/I515T mice showed highly elevated ABR thresholds compared to Otof+/+ mice (n=7-8 each; p<0.001 at 12kHz, Mann-Whitney-U-test). Grey dotted line as in A.E, Grand averages of ABR waveforms ± SEM in response to 80dB Click stimulation in mice aged 8 weeks. OtofI515T/I515T (n=8) have drastically reduced ABR amplitudes compared to Otof+/+ mice (n=7). Otof-/- mice have no ABR (green, n=9).F, Mean ABR wave I amplitude ± SEM for different stimulus intensities for 8 week and 25 week old OtofI515T/I515T and Otof+/+ mice (p<0.001, 2-way ANOVA).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A,B, No difference in voltage dependent Ca2+-currents (A) and fractional activation of ICa-channels (B) between OtofI515T/I515T IHCs (n=16) and IHCs of Otof+/+ littermates (n=13).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "D, Upper panel, while for stimuli up to 20ms exocytosis from OtofI515T/I515T (n=13) and Otof+/+ (n=11) IHCs was similar, sustained exocytosis, representing most likely the release of replenished vesicles, was significantly reduced in OtofI515T/I515T IHCs (t-test). Lower panel, Ca2+-current integrals were of similar size.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "E, Flash photolysis of caged Ca2+ elicited a smaller exocytic response in OtofI515T/I515T IHCs.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "F, The kinetics of the fast component from E was comparable between OtofI515T/I515T IHCs and Otof+/+ littermates (b). Open circles represent previously published data on IHCs of hearing wild-type mice (a; Beutner et al, 2001; Pangrsic et al, 2010).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A, Spontaneous rates of SGNs from OtofI515T/I515T (red, n=35) and Otof+/+ littermates (black, n=39) were not significantly different (p=0.83, Kolmogorov-Smirnov test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "B-D, Averaged poststimulus time histograms ±SEM from OtofI515T/I515T mice (n=25-32) and Otof+/+ littermate SGNs (n=13-27) to stimulation with 50ms tone bursts at the characteristic frequency (CF) of each fiber, 30dB above threshold at indicated stimulus rates.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "G, Spike rate increases with rising stimulus intensity were significantly shallower in OtofI515T/I515T SGNs, both for repetitive stimulation with 50ms tone bursts (left, p=0.014, t-test) and for continuous stimulation with amplitude modulated tones (right, p<0.001, Mann-Whitney U test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "H, Phase locking to amplitude modulated tones (assessed as the maximal synchronization index) was typically less precise in OtofI515T/I515T SGNs than in Otof+/+SGNs (p=0.09, Mann-Whitney U test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "I, 100ms masker tone and 15ms probe tones (both at CF, 30dB above threshold) were separated by silent intervals of variable duration. Inter-masker intervals were 500ms for Otof+/+, and 1000ms for OtofI515T/I515T. The ratio of probe and masker onset responses revealed enhanced RRP depletion after stimulation in OtofI515T/I515T (pink; mean ±SEM red) compared to Otof+/+ (grey; mean ±SEM black; for 4ms interval: p=0.001, t-test) and a slowed time course of recovery (x: half time of recovery, taken from normalized recovery functions; p<0.001, Mann-Whitney U test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "K, Mice learned to drink water when continuous noise was present but avoided drinking when the noise was interrupted by silent gaps. 5 OtofI515T/I515T mice (pink, mean ±SEM red) avoided drinking less efficiently than 2 Otof+/+ mice (grey, mean ±SEM black) for shorter gap durations. See also Figs S2/S3.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A, Exemplary ABR traces (Click 100dB) from one OtofI515T/I515T mouse recorded at indicated bullatemperatures during local heating. Note that ABRs never disappeared completely, but wave I amplitude changed reversibly with temperature.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "B,C, ABR wave I amplitudes in OtofI515T/I515T (A, Click 100dB) and Otof+/+ mice (B, Click 80dB) decreased with increasing temperature in the bulla. Each color represents a different experiment, dashed lines are line fits. Open symbols indicate the beginning of the experiments; subsequent recordings are connected by lines. The four indicated data points in B correspond to ABRs in A.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "D, Explanted organ of Corti from an Otof+/+ mouse at P4 after two days in vitro (DIV2) at 37°C immunostained against otoferlin (magenta) and Vglut3 (green). Note the intense immunostaining of otoferlin at the plasma membrane. Scale bar 10 µm.E-J, Explanted organs of Corti from Otof-/- mice at P4 were transfected by GeneGun with otoferlin cDNA and eGFP and immunostained at DIV2.E, Example cell transfected with wild-type mouseotoferlin cDNA.F,G, Representative cells transfected with mouseotoferlin including the 20 amino acids of the RXR motif (see Fig EV4). Cells in G were incubated at 38.5°C for 30 min prior to fixation. The RXR-otoferlin transfected cells show a membrane localization of otoferlin surrounding the Vglut3 immunofluorescence/eGFP fluorescence at the basal pole of the cells (arrows), similar as in controls (A,B).H,J, Both the human RXR motif and the Ile515Thr mutation were introduced in mouse cDNA, and cells were incubated at 37°C (H) or for 30min at 38.5°C (J) before fixation. Here, green fluorescence surrounds the otoferlin immunofluorescence (arrows), suggesting loss of otoferlin from the plasma membrane.K, Quantification of the relative plasma membrane levels of otoferlin (as in Fig 1) revealed normal plasma membrane abundance when the human RXR motif was present, but a strong reduction for otoferlin with RXR and Ile515Thr (individual cells; mean ±SEM; t-test).",
    "ncbi_link": "Otof: 9381
Otof: 9381///83762"
  },
  {
    "caption": "A-E, Capacitance increments recorded from Otof+/+ (black) and OtofI515T/I515T (red) IHCs. Individual cells recorded at indicated temperatures (light circles), mean ±SEM for perforated patch clamp experiments (t-test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "F,G, Summary of the capacitance changes and Ca2+-current integrals for Otof+/+ (F) and OtofI515T/I515T IHCs (G) at the different temperatures illustrates the drastic increase in exocytosis for physiological temperature. *Significant differences compared to RT measurements are indicated with colors of the respective temperature, and between PT and high temperature in violet (t-test).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "H-J, Otoferlin immunofluorescence in Otof+/+ IHCs (upper panel) and OtofI515T/I515T IHCs (middle and lower panels) of explanted organs of Corti at P7-P8 after incubation at indicated temperatures for 24h; maximum projections of z-stacks, inverted images, scale bar 10µm. The same imaging settings have been applied in all experiments, and the same lookup table was applied for the upper and middle panels. Images of lower panels are enhanced compared to middle panels (lookup table covering full data range of only this genotype) to visualize otoferlin distribution.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "H-J, Otoferlin immunofluorescence in Otof+/+ IHCs (upper panel) and OtofI515T/I515T IHCs (middle and lower panels) of explanted organs of Corti at P7-P8 after incubation at indicated temperatures for 24h; maximum projections of z-stacks, inverted images, scale bar 10µm. The same imaging settings have been applied in all experiments, and the same lookup table was applied for the upper and middle panels. Images of lower panels are enhanced compared to middle panels (lookup table covering full data range of only this genotype) to visualize otoferlin distribution.K, Quantification of otoferlin immunofluorescence in Otof+/+ IHCs (black bars, n=98-137 cells, 4-5 experiments) and OtofI515T/I515T IHCs (red bars, n=90-97 cells; Kruskal-Wallis test as in L-N), indicate reduced protein levels with increasing temperature.L, Apical/basal otoferlin protein distribution, revealing a significant apical shift of otoferlin and Vglut3 for OtofI515T/I515T IHCs (red symbols) at 38.5°C compared to Otof+/+ (grey/black symbols).M, Relative levels of membrane bound otoferlin were lowered with increasing temperature.N, Absolute otoferlin membrane immunostaining strongly decreased with temperature.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A-C, Pre-embedding immunogold labelling for EM visualizes otoferlin localization in random ultrathin sections through the basal part of IHCs in Otof+/+ (A) and OtofI515T/I515T (B) but not in Otof-/- (C) mice. IHCs are highlighted in beige. Scale bar 100nm.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "I,J, Some otoferlin labelled structures bear clathrin coats (red arrowheads), suggesting that they originate from bulk endocytosis. Scale bar 100nm.K, Otoferlin labelled vesicles were on average larger in OtofI515T/I515T IHCs (OtofI515T/I515T, n=86 vesicles, 18 images; Otof+/I+, n=82 vesicles, 6 images; Wilcoxon-rank-sum-test, as in L-M).L, Quantification of immunogold clusters at the plasma membrane revealed a strong trend towards reduced levels of otoferlin in OtofI515T/I515T (6 images each).M, Distal from the plasma membrane, immunogold labels were reduced in OtofI515T/I515T IHCs.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "N, Representative electron micrographs of IHCribbon synapses in OtofI515T/I515Tand Otof+/ (conventional embedding without immunogold) after pre-incubation for 10min at the indicated temperature followed by high K+ stimulation or 0 Ca2+ inhibition for 1min 45sec. Scale bars 100nm.",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "F-I, 3D reconstruction of the membrane-proximal pool (top view) and J-M, the ribbon-associated pool of vesicles (front view). Active zone membrane is depicted in blue, presynaptic density in pink, and ribbons in red, scale bars 100nm.N-Q, Cumulative probability distribution of the diameter of round vesicles as well as the longest axis of flattened vesicles in the membrane-proximal pool (N-O) and ribbon-associated pool (P-Q). N-P, one way ANOVA followed by Tukey's test; Q, Kruskal-Wallis test. Round vesicles tested in both the pools appeared larger in OtofI515T/I515T IHC synapses but the long axis of flattened vesicles were comparable for both the genotypes (see also Table EV1).",
    "ncbi_link": "Otof: 83762"
  },
  {
    "caption": "A RT-qPCR reveals that miR-210 was increased in lungs of mice with PH triggered by various conditions: VHL−/− as compared with VHL+/+ mice (N = 4/group), ***P < 0.0001 (first graph); hypoxia + SU5416 (Hyp + SU5416) (N = 6/group) as compared with normoxia + SU5416 (Norm + SU5416) (N = 7/group), **P = 0.0015 (second graph); Il6 transgenic versus littermate control mice (N = 4/group), **P = 0.0097 (third graph); and S. mansoni-infected mice (N = 4) compared with non-infected control mice (N = 5), ***P < 0.0001 (fourth graph).",
    "ncbi_link": "Il6: 16193
miR-210: 387206
VHL: 22346"
  },
  {
    "caption": "B From animal subjects in (A), in situ hybridization (ISH, purple stain) revealed increased miR-210 in < 100-μm pulmonary vessels of mice suffering from PH, *P = 0.0493 for first graph, **P = 0.0015 for second graph, *P = 0.0391 for third graph.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "C Representative ISH stain of miR-210 in < 100 μm pulmonary vessels of mice (bottom micrographs) exposed to Hyp + SU5416 compared with Norm + SU5416 (α-smooth muscle actin stain from serial sections, top row of micrographs).",
    "ncbi_link": "α-smooth muscle actin: 11475
miR-210: 387206"
  },
  {
    "caption": "D Increased miR-210 in < 200-μm remodeled pulmonary vessels of patients suffering from PAH (N = 19, Supplementary Table S1) as compared with non-PAH donor control lung (N = 10). Serial staining with hematoxylin and eosin is displayed in the top row of micrographs; quantification of miRNA ISH, right graph, *P = 0.0167.",
    "ncbi_link": "miR-210: 406992"
  },
  {
    "caption": "E Increased levels of miR-210 in plasma drawn from the pulmonary circulation (pulmonary capillary wedge position, PCWP) of patients with elevated mean pulmonary arterial pressures (mean PAP ≥ 25 mmHg) compared with control subjects (mPAP < 25 mmHg, N = 5/group, demographics in Supplementary Table S2), *P = 0.0357.",
    "ncbi_link": "miR-210: 406992"
  },
  {
    "caption": "F From animals in (C) immunohistochemistry (IHC) revealed that the miR-210 targets ISCU1/2 were reciprocally down-regulated in miR-210-enriched remodeled pulmonary vessels-namely in PH mice exposed to Hyp + SU5416 (F, ***P = 0.0002).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "G From humans in (D), immunohistochemistry (IHC) revealed that the miR-210 targets ISCU1/2 were reciprocally down-regulated in miR-210-enriched remodeled pulmonary vessels-namely in human PAH patients (G, ***P = 0.0008).",
    "ncbi_link": "miR-210: 406992"
  },
  {
    "caption": "H, I miR-210 expression (H) was increased (***P = 0.0003), and ISCU1/2 expression (I) was decreased (***P < 0.0001) in PECAM+pulmonary vascular endothelial cells isolated from PH mice (Hyp + SU5416) as compared with control (Norm + SU5416) (N = 4/group, left bars).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "After lentiviral delivery of GCN4 or GRX2 sensor genes to human PAECs, cellular fluorescence was measured by flow cytometry. Unlike control GCN4 sensors that homodimerized independent of Fe-S levels and induced consistent fluorescence, fluorescence derived from the GRX2 Fe-S-dependent sensors decreased in hypoxia, as displayed in representative flow cytometric plots (left) and by quantification of percentage of positive cells [(cell number in M2 gate)/(total cell number) × 100]. Immunoblotting revealed consistent expression of either GRX2 or GCN4 sensors (FLAG-tagged) in hypoxia (Hyp) compared with normoxia (Norm) (N = 3, ***P < 0.0001 for GRX2; N = 3, NS P = 0.1848 for GCN4).In contrast to consistent fluorescence from control GCN4 sensors, Fe-S-dependent GRX2 sensor fluorescence was decreased by siRNA knockdown of ISCU1/2 (siISCU) as compared with control (siCont) (N = 3, ***P < 0.0001 for GRX2; N = 3, NS P = 0.1790 for GCN4).",
    "ncbi_link": "GCN4: 856709
GRX2: 51022
ISCU1/2: 23479"
  },
  {
    "caption": "GRX2, but not GCN4, sensor fluorescence was decreased after transfection of miR-210 oligonucleotide mimic (miR-210) as compared with control (miRC) (N = 3, ***P = 0.0002 for GRX2; N = 3, NS P = 0.0913 for GCN4). During hypoxic exposure, GRX2, but not GCN4, sensor fluorescence was increased after transfection of an antisense miR-210 inhibitor (AS210) as compared with control (ASC) (N = 3, **P = 0.003 for GRX2; N = 3, NS P = 0.1194 for GCN4).",
    "ncbi_link": "GCN4: 856709
GRX2: 51022
miR-210: 406992"
  },
  {
    "caption": "By electron paramagnetic resonance (EPR) spectroscopy (representative VHL−/− versus control lung), Fe-S cluster signal was decreased (left graph) in VHL−/− mice lung tissue (VHL−/−, N = 3) as compared with WT control lung tissues (WT, N = 5), ***P = 0.0003.",
    "ncbi_link": "VHL: 22346"
  },
  {
    "caption": "B By immunohistochemistry (IHC), ISCU1/2 was unchanged in < 100 μm pulmonary vessels of miR-210−/−mice exposed to Hyp + SU5416 (N = 6) versus Norm + SU5416 (N = 7), NS P = 0.2833.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "C Fe-S-dependent Complex I-specific activity was decreased in WT PH mice as compared with control (N = 7/group, left bars, ***P < 0.0001), but activity was preserved in the lungs of miR-210−/−mice in either condition (N = 8/group, right bars), NS P = 0.3693.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "D IHC demonstrated that pulmonary vascular GLUT1 was increased in WT PH mice (left bars, ***P = 0.0006), but GLUT1 was unchanged in miR-210−/− mice in either condition (right bars, NS P = 0.9967).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "E 3-nitrotyrosine (3-NT) was increased in pulmonary vessels of WT PH mice but was reduced in miR-210−/− mice in either condition (N = 6/group) (***P < 0.0001, NS P = 0.4087).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "F In PH conditions, endothelin-1 was decreased in miR-210−/− lung tissue compared with WT tissue (N = 5/group), **P = 0.007.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "G PCNA was increased in WT PH pulmonary vessels but was decreased in miR-210−/− tissue exposed to either condition (N = 5/group) (**P = 0.0096, *P = 0.0124, *P = 0.0263 for miR-210−/−).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "I Unlike WT mice (black bars) demonstrating increased right ventricular systolic pressure (RVSP) after Hyp + SU5416 (N = 10) versus Norm + SU5416 (N = 11), hemodynamic dysregulation was significantly alleviated in miR-210−/− mice (white bars, N = 11) (***P < 0.0001, *P = 0.0258, **P = 0.0059).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "J Compared with WT controls (N = 9), miR-210−/− mice (N = 8) displayed a blunted increase of the Fulton index (RV/LV + S) under PH versus baseline conditions (expressed as a ratio of RV/LV + S under Hyp + SU5416 versus Norm + SU5416, *P = 0.031).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "K-M Under PH (black bars, N = 8/group) versus baseline conditions (white bars, N = 6/group), pulmonary vascular remodeling was alleviated in miR-210−/− mice, as visualized via histology (L), and confirmed by decreased % arteriolar muscularization (K, **P = 0.001, **P = 0.0045 for miR-210−/−, *P = 0.0158) and decreased vessel wall thickness (M, ***P < 0.0001, **P = 0.0086).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "B, C Intrapharyngeal delivery of miR-210 mimic increased miR-210 in whole lung (***P = 0.0002) (B) and in < 100-μm pulmonary vessels (**P = 0.007) (C).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "D miR-210 mimic also repressed ISCU1/2 levels in those same caliber vessels (N = 6/group), **P = 0.0022.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "E Endothelin-1 was increased in mouse lung tissue after delivery of miR-210 mimic (N = 6/group), *P = 0.0368.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "F-H miR-210 mimic delivery increased RVSP (N = 8/group) (F) and vascular remodeling (α-smooth muscle actin stain, α-SMA), as evidenced by increased percent of muscularized (< 100 μm) pulmonary vessels (G) and increased medial thickening relative to vessel diameter when compared with miR-Control (H) (N = 6/group). **P = 0.0021 for (F), **P = 0.0072 for (G), *P = 0.0335 for (H).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "B-D Intravenous delivery of anti-miR-210 down-regulated miR-210 expression in whole lung tissue (N = 7/group), ***P < 0.0001 (B), the pulmonary vasculature as assessed by in situ staining (N = 7/group), ***P = 0.0003 (C), and PECAM+vascular endothelial cells derived from whole lung tissue (N = 4/group), **P = 0.0013 (D).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "E Correspondingly, anti-miR-210 delivery resulted in preservation of ISCU1/2 expression in < 100-μm pulmonary vessels as compared to anti-miR-Control (N = 5/group), **P = 0.0011.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "F Similarly, ISCU1/2 expression was preserved in PECAM+ endothelial cells derived from mice treated with anti-miR-210 (N = 4/group), **P = 0.0016.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "G Endothelin-1 was decreased in lung tissue from mice treated with anti-miR-210 during Hyp + SU5416 exposure (N = 6/group), *P = 0.0181.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "H As assessed by in situ immunofluorescence, PCNA was decreased in pulmonary vessels (< 100 μm) after anti-miR-210 delivery, **P = 0.001.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "I-K Anti-miR-210 delivery (N = 10/group) ameliorated the elevation of RVSP, **P = 0.0031 (i) and vascular remodeling, as reflected by increased percent of muscularized arterioles (N = 8/group, **P = 0.0091) (J) and increased medial thickness relative to vessel diameter in < 100-μm pulmonary vessels (N = 6/group, **P = 0.0021) (K).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "I-K Anti-miR-210 delivery (N = 10/group) ameliorated the elevation of RVSP, **P = 0.0031 (i) and vascular remodeling, as reflected by increased percent of muscularized arterioles (N = 8/group, **P = 0.0091) (J) and increased medial thickness relative to vessel diameter in < 100-μm pulmonary vessels (N = 6/group, **P = 0.0021) (K).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "M Pharmacologic inhibition of miR-210 (N = 7/group) down-regulated pulmonary expression of miR-210, ***P < 0.0001 (M).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "N Pharmacologic inhibition of miR-210 (N = 7/group) preserved ISCU1/2 expression in < 100-μm pulmonary vessels, **P = 0.0015 (N).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "O-Q In contrast to anti-miR-Control (N = 8), anti-miR-210 ameliorated the elevation of RVSP (N = 10/group, ***P < 0.0001) (O) and lung remodeling (N = 7/group, **P = 0.0022, *P = 0.0167) (P-Q).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "A Following the schema of Fig5A in the presence of hypoxia but the absence of SU5416, intravenous delivery of anti-miR-210 ameliorated the elevation of RVSP compared with anti-miR-Control (N = 6/group, ***P = 0.001).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "C, D Consistent with specific delivery to the vascular endothelium after intravenous administration (Dahlman et al, 2014), 7C1-mediated delivery of anti-miR-210 (N = 6/group) decreased miR-210 expression in PECAM+ pulmonary vascular endothelial cells, **P = 0.0013, (D) but not PECAM-negative pulmonary cells, NS P = 0.3775 (C).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "E Correspondingly, endothelial-specific anti-miR-210 (N = 6/group) increased ISCU1/2 expression in PECAM+ cells even in the presence of chronic hypoxia, ***P = 0.0003.",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "F-I Delivery of anti-miR-210 (N = 5/group) decreased endothelin-1 in hypoxic mouse lung tissue, *P = 0.0198 (F). As a result, in contrast to anti-miR-Control (N = 8), endothelial-specific anti-miR-210 ameliorated the elevation of RVSP (N = 6), **P = 0.0024 (G), and pulmonary vascular remodeling (N = 6/group), **P = 0.0021, *P = 0.0117 (H-I).",
    "ncbi_link": "miR-210: 387206"
  },
  {
    "caption": "B, C Pharmacologic inhibition of ISCU (N = 8/group) did not influence miR-210 expression in the lungs either after Norm + SU5416, NS P = 0.8634 (B) or Hyp + SU5416, NS P = 0.9786 (C).",
    "ncbi_link": "ISCU: 66383
miR-210: 387206"
  },
  {
    "caption": "D As compared with control siRNA (siCont) where ISCU1/2 expression was decreased after exposure to Hyp + SU5416 (white bars), lung delivery of siRNA specific for ISCU1/2 (siISCU) via Staramine-mPEG nanocomplexes (Polach et al, 2012) down-regulated ISCU1/2 in < 100-μm pulmonary vessels in Norm + SU5416 and Hyp + SU5416 (N = 5/group, ***P = 0.0006, **P = 0.0019 for Hyp + SU5416, **P = 0.0029 for siCont).",
    "ncbi_link": "ISCU: 66383
ISCU1/2: 66383"
  },
  {
    "caption": "E By electron paramagnetic resonance (EPR) spectroscopy (representative siCont versus siISCU lung), Fe-S cluster signal was decreased (quantitative graph, right) in siISCU mouselung tissue (N = 4 mice) compared with siCont (N = 5 mice), *P = 0.0143.",
    "ncbi_link": "ISCU: 66383"
  },
  {
    "caption": "F Endothelin-1 was increased in lung tissue after siISCU delivery under normoxic conditions (N = 5/group), **P = 0.0027.",
    "ncbi_link": "ISCU: 66383"
  },
  {
    "caption": "G-I In the absence (left bars) and presence (right bars) of Hyp + SU5416 for 2 weeks, siISCU (black bars) induced elevations in RVSP (***P < 0.0001, **P = 0.0031) (G) and increased pulmonary vascular remodeling in < 100-μm pulmonary vessels (H, I) as compared with siCont (N = 5/group, ***P = 0.0003, *P = 0.0114 for H; ***P = 0.0006, **P = 0.0098 for I).",
    "ncbi_link": "ISCU: 66383"
  },
  {
    "caption": "G-I In the absence (left bars) and presence (right bars) of Hyp + SU5416 for 2 weeks, siISCU (black bars) induced elevations in RVSP (***P < 0.0001, **P = 0.0031) (G) and increased lung remodeling in < 100-μm pulmonary vessels (H, I) as compared with siCont (N = 5/group, ***P = 0.0003, *P = 0.0114 for H; ***P = 0.0006, **P = 0.0098 for I).",
    "ncbi_link": "ISCU: 66383"
  },
  {
    "caption": " (A,B) The blocking of the binding of WT PD-1-mFc (A) or N58A mutated PD-1-mFc (B) to PD-L1 transiently expressed on the surface of 293T cells are analyzed with varied concentrations of camrelizumab. The PD-L1 expressing 293T cells stained with PBS alone is used as negative controls, whereas the cells stained with WT or N58A mutated PD-1-mFc proteins are used as a positive control. The frequency of PD-1-mFc staining positive cells in PD-L1-GFP positive cells is labeled in the upright corner. The reduced frequency of the PD-L1-mFc-staining-positive subpopulation compared with positive control indicates the blockage of the PD-1/PD-L1 interaction. The density of events at a given position in the plot is color-coded, with red representing the highest number of events at that point in the graph, while yellow, green, and blue represent progressively lower event densities. The results presented here are representative of three independent experiments with similar results. ",
    "ncbi_link": "GFP: 
PD-L1: 29126
PD-1: 5133"
  },
  {
    "caption": "(A) UHMK1 levels in tumor tissues (T) and corresponding nontumor tissues (N) from five GC patients were analyzed using Western blotting and qRT-PCR. The relative mRNA expression of UHMK1 was presented as mean ± standard deviation from three replicates. Pairwise, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(B) Immunoblotting and qRT-PCR were used to measure the levels of UHMK1 in GES-1 and GC cell lines. The relative mRNA expression of UHMK1 was presented as mean ± standard deviation from three replicates. Pairwise, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "A) GC cells (SGC7901 and MGC803) were transfected with (A) shUHMK1-#1,-#2, -#3, or control shRNA lentiviral vector, or (B) with a shRNA-resistant expression construct, UHMK1Δ. Western blotting was used to measure the levels of UHMK1. NIH ImageJ software was used to quantify the band intensity. Western blotting assay were conducted for three replicates. SGC7901 cells were transfected with or without shUHMK1-#1 or the shRNA-resistant expression construct UHMK1Δ. CCK-8 assays were conducted. Scale bars=5mm. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "SGC7901 cells were transfected with or without shUHMK1-#1 or the shRNA-resistant expression construct UHMK1 colony formation assays were conducted. Scale bars=5mm. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(D and E) The volumes of subcutaneous gastric tumors derived from SGC7901 cells in NOD/SCID mice were determined at different time points. Tumors and representative bioluminescence images are also shown. UHMK1 silencing in the mouse model was confirmed by western blotting (three biological replicates). Data were presented as mean ± standard deviation from shcontrol and shUHMK1#1 mice (n = 10 mice/group). Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Scale bars=1cm.. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(F, G) UHMK1 silencing (F) and overexpression (G) affected GC cell abdominal metastasis. The quantitative number of metastatic nodules (left panel) in nude mice (n = 10 mice/group). Representative images of abdominal metastases are also shown (right panel). Scale bars=1cm. Data information: **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(B) LC-MS/MS was used to examine the metabolites in SGC7901 cells with or without UHMK1 knockdown. The data are shown in the heatmap.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(C) (upper panel) LC-MS/MS analysis was performed to measure 15N-glutamine-labeled purine synthesis intermediates in BGC823 cells transfected with or without the WT-UHMK1 or UHMK1-K54R constructs. (lower panel) LC-MS/MS was used to analyze metabolites labeled with 13C-glycine in BGC823 cells transfected with or without the WT-UHMK1 or UHMK1-K54R constructs(three biological replicates). Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(D) RNA and DNA with incorporated 14C-glycine in BGC823 cells transfected with or without the WT-UHMK1 or UHMK1-K54R constructs were examined using LC-MS/MS(three biological replicates). Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(E) qRT-PCR assays were used to analyze the effects of WT-UHMK1 or UHMK1-K54R on the genes controlling purine metabolism. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(F) UHMK1 silencing significantly decreased SGC7901 cell proliferation, while ATIC overexpression or purine supplementation markedly reversed this inhibition. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. . Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "ATIC: 471
UHMK1: 127933"
  },
  {
    "caption": "(G) Treatment with the ATIC inhibitor significantly reversed the proliferation of BGC823 cells induced by UHMK1 overexpression. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(A) (Ai) Western blot analysis was used to confirm UHMK1 overexpression and ATF4 knockdown in BGC823 cells. (Aii) Silencing ATF4 significantly decreased the levels of the indicated metabolites in BGC823 cells overexpressing UHMK1(three biological replicates). (Aiii) Silencing ATF4 significantly decreased the levels of RNA and DNA containing U-14C-glycine in BGC823 cells overexpressing UHMK1(three biological replicates). (B) LC-MS/MS was used to examine the metabolites in SGC7901 cells with or without UHMK1 knockdown or ATF4 reintroduction. The data are shown in the heatmap. (C) Silencing ATF4 significantly decreased the levels of the indicated genes in BGC823 cells overexpressing UHMK1. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. (D) (Di) qRT-PCR was used to measure the expression of ATF4 in BGC823 cells overexpressing UHMK1. (Dii) UHMK1 overexpression enhanced the nuclear translocation of ATF4 in BGC823 cells. (Diii) ChIP assays on the ATIC and PPAT promoters were performed in BGC823 cells with the indicated antibody. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "ATF4: 468
ATIC: 471
PPAT: 5471
UHMK1: 127933"
  },
  {
    "caption": "(E) Silencing ATF4 markedly decreased the proliferation of BGC823 cells overexpressing UHMK1. (left panel) The quantitative number of colonies formed in scramble+Flag, scramble+Flag-UHMK1, siATF4+Flag and siATF4+Flag-UHMK1 group. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. (right panel) Representative images of colonies are shown. Scale bars=5mm. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "Flag: 
ATF4: 468
UHMK1: 127933"
  },
  {
    "caption": "(F) Silencing ATF4 markedly decreased the migration of BGC823 cells with UHMK1 overexpression. (left panel) The quantitative number of migrated cells in scramble+Flag, scramble+Flag-UHMK1, siATF4+Flag and siATF4+Flag-UHMK1 group. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. (right panel) Representative images of migrated cells in each group are shown. Scale bars=100μm. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "Flag: 
ATF4: 468
UHMK1: 127933"
  },
  {
    "caption": "(G) Silencing ATF4 markedly decreased the invasion of UHMK1 overexpressing BGC823 cells. (left panel) The quantitative number of invaded cells in scramble+Flag, scramble+Flag-UHMK1, siATF4+Flag and siATF4+Flag-UHMK1 group. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. (right panel) Representative images of invaded cells in each group are shown. Scale bars=100μm. Data information: *P< 0.05, **P< 0.01, ***P< 0.001, # marked no significance.",
    "ncbi_link": "Flag: 
ATF4: 468
UHMK1: 127933"
  },
  {
    "caption": "(E) Silencing UHMK1 in SGC7901 cells via UHMK1-siRNA. NCOA3 phosphorylation at S1062/T1067 was measured with a special Ab that recognizes phosphorylated NCOA3-S1062/T1067.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(A) Knockdown of UHMK1 blocked NCOA3 binding to ATF4. SGC7901 cells were treated as indicated. Co-IP was carried out with mouse immunoglobulin G (IgG) or anti-NCOA3 antibody. Then Western blotting was performed.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(B) BGC823 cells were transfected with Flag-NCOA3 or NCOA3-S1062A/T1067A with or without His-tagged UHMK1. Co-IP was performed using an anti-Flag antibody.",
    "ncbi_link": "Flag: 
His: 
NCOA3: 8202
UHMK1: 127933"
  },
  {
    "caption": "(E) (Ei) ChIP data from BGC823 cells are presented as indicated. (Eii) NCOA3-S1062/T1067 phosphorylation by UHMK1 enhanced the expression of critical genes as indicated (three biological replicates). (F) (Fi and Fii) The effects of WT-NCOA3 and the NCOA3-S1062A/T1067A, and NCOA3-S1062E/T1067E mutants on BGC823 cell proliferation, invasion, and migration (three biological replicates). Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test.Data represent mean ± SD. *P< 0.05, **P< 0.01, ***P< 0.001.",
    "ncbi_link": "NCOA3: 8202
UHMK1: 127933"
  },
  {
    "caption": "(G, H) The effects of WT-NCOA3, and the NCOA3-S1062A/T1067A, and NCOA3-S1062E/T1067E mutants on GC growth and metastasis in the mouse model (n = 10 mice/group). Scale bars=1cm. Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test.Data represent mean ± SD. *P< 0.05, **P< 0.01, ***P< 0.001.",
    "ncbi_link": "NCOA3: 8202"
  },
  {
    "caption": "(A) SGC7901 and MGC803 cells were transfected with ATF4 shRNA or shcontrol. Western blottings and qRT-PCR were used to analyze the expression of UHMK1. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data information: Data represent mean ± SD. **P< 0.01, ***P< 0.001.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "(B) Overexpression of ATF4 enhanced the expression of UHMK1 in BGC823 and HGC27 cells. Data were presented as mean ± standard deviation from three replicates. Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data information: Data represent mean ± SD. **P< 0.01, ***P< 0.001.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "(D) The effect of ATF4 on the activity of the WT-UHMK1 promoter and its mutations, as evaluated by using luciferase reporter assays. Data information: Data represent mean ± SD. **P< 0.01, ***P< 0.001.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(E) ChIP assays were used to examine the binding of ATF4 to the UHMK1 promoter in SGC7901 and MGC803 cells. Input DNA and nonspecific IgG were included as controls.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(F) ATF4 deficiency and overexpression regulated the activity of the UHMK1 promoter in GC cells. Data information: Data represent mean ± SD. **P< 0.01, ***P< 0.001.",
    "ncbi_link": "ATF4: 468
UHMK1: 127933"
  },
  {
    "caption": "(A) qRT-PCR was performed to analyze UHMK1 expression in BGC823 cells infected with or without H. pylori CagA+ strains 7.13 and J166. MOI, multiplicity of infection. Data were presented as mean ± standard deviation from three replicates. Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data represent mean ± SD. *P< 0.05, **P< 0.01,.",
    "ncbi_link": "UHMK1: 127933"
  },
  {
    "caption": "(C) PMSS1, a H. pylori strain, was used to challenge mice orogastrically, with Brucella broth as the control. qRT-PCR was performed to measure UHMK1 (Ci) and PMSS1(Cii) expression in gastric tissues. Data were presented as mean ± standard deviation from three replicates. Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data represent mean ± SD. *P< 0.05, **P< 0.01,.",
    "ncbi_link": "UHMK1: 16589"
  },
  {
    "caption": "(D) Immunoblotting of UHMK1, NCOA3 phosphorylated at S1062/T1067, NCOA3, and ATF4 in the samples (E) An ATF4 luciferase reporter assay was carried out in BGC823 cells with or without H. pylori infection. Data were presented as mean ± standard deviation from three replicates. (F) (Fi) The domain architecture of UHMK1 and the positions of human GC-associated mutations. (Fii and Fiii) IP kinase assay. Briefly, UHMK1 from HEK293 cells expressing WT-UHMK1 or its mutants was immunoprecipitated with anti-HA antibodies. The immunoprecipitated proteins were mixed with a synthetic peptide of the CATS protein (a known substrate of UHMK1) and [32P] ATP. A phosphocellulose paper assay was used to measure kinase activity. The results were normalized to a value of 1.0 for WT-UHMK1(three biological replicates). (G) The effects of human GC-associated UHMK1 mutations on the proliferation and colony formation of GC cells (three biological replicates). (H) The effects of human GC-associated UHMK1 mutations on GC cell invasion and migration (three biological replicates). Data information: Unpaired, two-tailed statistical significance was assessed by Student's t‐test. Data represent mean ± SD. *P< 0.05, **P< 0.01,. ",
    "ncbi_link": "luciferase: 
ATF4: 468
UHMK1: 127933"
  },
  {
    "caption": "(A) Images showing UHMK1, p-NCOA3 (S1062/T1067), and ATIC protein expression in two human GC specimens. Scale bars=100μm. (B) Pearson correlation analysis about of the levels of UHMK1, p-NCOA3 (S1062/T1067) and ATIC proteins in patients with GC (n=120) by IHC. ",
    "ncbi_link": "ATIC: 471
UHMK1: 127933"
  },
  {
    "caption": "F. Relative expression of Lmnb1 and Tubb3 revealed by qRT-PCR from NPCs and differentiating neurons at the indicated days. ***P < 0.001, **P < 0.01, *P < 0.05, one sample t-test (n = 4).",
    "ncbi_link": "Lmnb1: 16906
Tubb3: 22152"
  },
  {
    "caption": "Open field (OF) test. (B) Color-coded distribution of the exploratory path in the open field test. X-Y axes of squares correspond to the OF arena. Old WT mice as well as Lmnb1-cKO mice spend more time in the periphery of the OF arena.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "Open field (OF) test. (C) Total distance traveled during the OF test. No significant difference among groups. F(2, 25) = 2.23, P = 0.13, ANOVA. (D) Velocity of travel during the OF test. F(2, 25) = 1.60, P = 0.22, ANOVA. N.S. (not significant). (E) Fraction of time spent in the periphery. F(2, 25) = 10.71, P = 0.00044, ANOVA followed by Tukey Kramer, ** P < 0.01. (F) Fraction of traveled distance in the periphery, F(2, 25) = 3.84, P = 0.035, ANOVA followed by Tukey Kramer, * P < 0.05 (n: WT = 10, WT-old =7, Lmnb1-cKO = 11 for the OF test).",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "H-J. Novelty suppressed feeding. (H) Total feeding time during the NSF test, P = 0.0068, Kruskal-Wallis test followed by Dunn's test. ** P < 0.01. (n: WT = 6, WT-old =7, Lmnb1-cKO = 6 for novelty suppressed feeding). (I) Food consumption during the NSF test, P = 0.014, Kruskal-Wallis test followed by Dunn's test. * P < 0.05. (J) Total number of feeding instances during NSF test. N.S. (not significant).",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "MA plot of differentially expressed genes between control and Lmnb1-KO NPCs.",
    "ncbi_link": "Lmnb1: 16906"
  },
  {
    "caption": "E. Fraction of direction of gene regulation by LaminB1. Genes were allocated dependent on where LaminB1 interacts with genes. Red bars indicated upregulated genes and blue bars indicate downregulated genes after lamin B1 knockout.",
    "ncbi_link": "lamin B1: 16906
LaminB1: 16906"
  },
  {
    "caption": "Confirmation of Lamin B1 overexpression by qRT-PCR (*P = 0.020, n = 3, one-sample t-test)",
    "ncbi_link": "Lamin B1: 16906"
  },
  {
    "caption": "D, Relative induced expression of differentiation markers upon the withdrawal of FGF2. 0 % indicates the same expression levels with control. Exogenous expression of lamin B1 inhibits the induction of genes related to neural differentiation (Tuj1, *P = 0.023; Prox1, ***P = 0.00012; NeuroD1, ** P = 0.0046; Ascl1, ***P = 0.00064; S100β, ***P = 0.000097; n = 3, one-sample t-test).",
    "ncbi_link": "Ascl1: 17172
lamin B1: 16906
NeuroD1: 18012
Prox1: 19130
S100β: 20203
Tuj1: 22152"
  },
  {
    "caption": "F, Confocal images after exogenous expression of lamin B1 in EGFP+ cells with RV;LaminB1-IRES-GFP (laminB1-OE.) Scale bar = 20 µm.",
    "ncbi_link": "GFP: 
LaminB1: 16906
laminB1: 16906"
  },
  {
    "caption": "G, H, Exogenous expression of laminB1 repressed neuronal differentiation in vivo. An arrowhead indicate DCX+GFP+ cell in control (G, left) and open arrowheads indicate Sox2+GFP+ cells in lamin B1-OE cells. The fraction of EGFP+ DCX+ cells was significantly reduced by lamin B1 overexpression (***P < 0.0002, n = 3), whereas the fractions of EGFP+DCX+Sox2+ cells and the EGFP+Sox2+ were increased (EGFP+DCX+Sox2+, **P = 0.0024; EGFP+ Sox2+, P = 0.058; others, *P = 0.02). Scale bar = 20 µm.",
    "ncbi_link": "lamin B1: 16906
laminB1: 16906"
  },
  {
    "caption": "Mice were subjected to ONC and i.v.-injected with either an anti-VCAM-1 blocking antibody or an isotype control antibody. Eyes were collected after 2 or 3 days for Real-Time PCR analysis, respectively. (B) Expression ratios of Tnf, Il12a and Il1b, compared to Tgfb2, showing that blocking VCAM-1 results in skewing the retina towards a pro-inflammatory milieu after ONC. n = 11-13 per group. Data shown are representative of two independent experiments. Bar graphs throughout the figure show mean ± SE of each group. *, P < 0.05; **, P < 0.01; *** P < 0.001. noninj - noninjured control; ONC - optic nerve crush.",
    "ncbi_link": "Tgfb2: 
Il12a: 16159
Il1b: 16176
Tnf: 21926"
  },
  {
    "caption": "(D) Left: Time course of normalized mCherry signal, as assessed by TIRF microscopy, from GRAMD1 triple knockout (TKO) HeLa cells expressing mCherry-GRAM1b. Cells were pre-incubated with either control imaging buffer (for control) or imaging buffer containing purified ECFP-D4H proteins (3 µM) (for masking accessible PM cholesterol) for 30 min at 37°C and imaged with the same buffer conditions. SMase treatment (100 mU/ml) is indicated. Right: Values of ΔF/F0 corresponding to the end of the experiment as indicated by the arrow [mean ± SEM, n = 32 cells (Control), n = 35 cells (Pre-incubation w/ ECFP-D4H); data are pooled from two independent experiments for each condition; two-tailed unpaired Student's t-test, **P < 0.0001].",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(E) Left: Time course of normalized EGFP signal, as assessed by TIRF microscopy, from GRAMD1 triple knockout (TKO) HeLa cells expressing EGFP-GRAM1b together with either mCherry for control or mCherry-Lact-C2 for PS masking. SMase treatment (100 mU/ml) is indicated. Right: Values of ΔF/F0 corresponding to the end of the experiment as indicated by the arrow [mean ± SEM, n = 53 cells (mCherry), n = 32 cells (mCherry-Lact-C2 OE); data are pooled from four independent experiments for each condition; two-tailed unpaired Student's t-test, **P < 0.0001].",
    "ncbi_link": "Lact: 
mCherry: 
GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(F) Confocal images of live GRAMD1 TKO HeLa cells expressing either wild-type (WT) or mutant versions of EGFP-tagged GRAM domain of GRAMD1b (EGFP-GRAM1b) constructs as indicated. Cells were treated with SMase (100 mU/ml for 1 hour at 37°C) before imaging. Insets show at higher magnification the regions indicated by white dashed boxes. Anionic lipid sensing defective mutants (K161A, R191A, and K161A/R191A), a cholesterol sensing defective mutant (R189W), and a cholesterol/anionic lipid sensing defective mutant (R189W/R191A) are shown. Note the absence of (R189W, R189W/R191A, and K161A/R191A) or significantly reduced (K161A, R191A) PM recruitment of the mutant versions of EGFP-GRAM1b compared to the strong PM recruitment of wild-type EGFP-GRAM1b (WT). Scale bars, 10 µm.",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(G) Quantification of the ratio of PM EGFP-GRAM1b signals to the cytosolic EGFP-GRAM1b signals, as assessed by confocal microscopy and line scan analysis from GRAMD1 TKO HeLa cells expressing either wild-type (WT) or mutant versions of EGFP-GRAM1b with or without SMase treatment (100 mU/ml for 1 hour at 37°C) as shown in (F) and Appendix Fig S1B (mean ± SEM, n = 40 cells for WT, and n = 30 cells for other conditions; data are pooled from four independent experiments for WT and three independent experiments for the rest; two-tailed unpaired Student's t-test, **P < 0.0001. n.s. denotes not significant).",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(H) Left: Time course of normalized EGFP signal, as assessed by TIRF microscopy, from GRAMD1 TKO HeLa cells expressing either wild-type (WT) or mutant versions of EGFP-GRAM1b constructs as indicated. SMase treatment (100 mU/ml) is indicated. Right: Values of ΔF/F0 corresponding to the end of the experiment as indicated by the arrow [mean ± SEM, n = 126 cells (WT), n = 38 cells (K161A), n = 33 cells (R191A), n = 43 cells (K161A/R191A), n = 46 cells (R189W), n = 44 cells (R189W/R191A); data are pooled from six independent experiments for WT and two independent experiments for the rest; Dunnett's multiple comparisons test, **P = 0.0002 (WT vs. K161A) and **P < 0.0001 for the rest].",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(A) Lysates of wild-type (control) and GRAMD1 TKO (TKO) HeLa cells that stably expressed either EGFP or EGFP-GRAMD1b constructs as indicated [wild-type (WT), R189W mutant (R189W), R189W/R191A mutant (RW/RA)] were processed by SDS-PAGE and immunoblotted (IB) with anti-GFP, anti-GRAMD1b, and anti-actin antibodies.",
    "ncbi_link": "EGFP: 
GRAMD1b: 57476
GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(B) Confocal images of live GRAMD1 TKO HeLa cells stably expressing EGFP-GRAMD1b constructs as indicated that were additionally transfected with an accessible PM cholesterol biosensor, mCherry-tagged GRAM domain of GRAMD1b (mCherry-GRAM1b). Cells were treated with SMase (100 mU/ml for 1 hour at 37°C) before imaging. Insets show at higher magnification the regions indicated by white dashed boxes. Note the very weak PM recruitment of mCherry-GRAM1b in cells that stably expressed EGFP-GRAMD1b WT, compared to the strong PM recruitment of mCherry-GRAM1b in cells that stably expressed EGFP-GRAMD1b R189W mutant (R189W) or EGFP-GRAMD1b R189W/R191A mutant (RW/RA). Scale bars, 10 µm.",
    "ncbi_link": "mCherry: 
GRAMD1b: 57476
GRAMD1: 54762///57655///57476"
  },
  {
    "caption": "(C) Quantification of the ratio of PM mCherry-GRAM1b signals to the cytosolic mCherry-GRAM1b signals, as assessed by confocal microscopy and line scan analysis from GRAMD1 TKO HeLa cells expressing mCherry-GRAM1b with SMase treatment (100 mU/ml for 1 hour at 37°C) as shown in (B) and Fig EV3B (mean ± SEM, n = 20 cells for each condition; data are pooled from two independent experiments; Dunnett's multiple comparisons test, **P < 0.0001. n.s. denotes not significant).",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(D) Left: Time course of normalized mCherry signal, as assessed by TIRF microscopy, from GRAMD1 TKO HeLa cells stably expressing either EGFP or EGFP-GRAMD1b constructs as indicated that were additionally transfected with an accessible PM cholesterol biosensor mCherry-GRAM1b. SMase treatment (100 mU/ml) is indicated. Right: Values of ΔF/F0 corresponding to the end of the experiment as indicated by the arrow [mean ± SEM, n = 31 cells (EGFP), n = 28 cells (EGFP-GRAMD1b WT), n = 23 cells (EGFP-GRAMD1b R189W), n = 27 cells [EGFP-GRAMD1b R189W/R191A (RW/RA)]; data are pooled from two independent experiments for each condition; Dunnett's multiple comparisons test, **P < 0.0001 (EGFP vs. WT and WT vs. R189W), **P = 0.0002 (WT vs. RW/RA)].",
    "ncbi_link": "EGFP: 
mCherry: 
GRAMD1: 57655///54762///57476
GRAM1b: 57476
GRAMD1b: 57476"
  },
  {
    "caption": "(E) Wild-type (control) and GRAMD1 TKO (TKO) HeLa cells that stably expressed either EGFP or EGFP-tagged GRAMD1b constructs as indicated [wild-type (WT), R189W mutant (R189W), R189W/R191A mutant (RW/RA)], were cultured in the medium supplemented with 10% lipoprotein-deficient serum (LPDS) and mevastatin (50 µM) for 16 hours and then treated with SMase (100 mU/ml) for 3 hours at 37°C. Top: Lysates of the cells were processed for SDS-PAGE and IB with anti-SREBP-2 and anti-actin antibodies. Arrows indicate precursor (P) and cleaved (C) forms of SREBP-2. Bottom: The response rate was obtained by normalizing the ratio of the band intensity of the cleaved SREBP-2 over the total band intensity of cleaved and precursor forms of SREBP-2 from the cells with SMase treatment by the one from the cells without SMase treatment for each condition. Note that the suppression of SREBP-2 cleavage is attenuated in GRAMD1 TKO HeLa cells compared to wild-type control HeLa cells. Note also the rescue by expression of wild-type EGFP-GRAMD1b (WT) but not by mutant versions of EGFP-GRAMD1b [R189W, R189W/R191A (RW/RA)] [mean ± SEM, n = 4 lysates (independent experiments) for each condition; Dunnett's multiple comparisons test, **P = 0.0035 (Control + EGFP vs. TKO + EGFP), **P < 0.0001 (TKO + EGFP vs. TKO + WT), n.s. denotes not significant].",
    "ncbi_link": "EGFP: 
GRAMD1b: 57476
GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(F) Amphotericin B resistance of SMase-treated wild-type (control) and GRAMD1 TKO (TKO) HeLa cells that stably expressed either EGFP or EGFP-tagged GRAMD1b constructs as indicated [wild-type (WT), R189W mutant (R189W), R189W/R191A mutant (RW/RA)]. Left: Cells that had been pre-treated with SMase (100 mU/ml) for 3 hours at 37°C were treated with indicated concentration of Amphotericin B for 20 min at 37ºC. After overnight recovery in culture media, cell viability was measured by detecting ATP present in each well via luminescence (see Materials and Methods). The same number of cells were seeded in each well before SMase treatment. Note the reduced viability of cells with increasing amount of Amphotericin B. Right: Quantification of cell viability with increasing amount of Amphotericin B. Note the resistance of wild-type control and GRAMD1 TKO cells that stably expressed EGFP-GRAMD1b (WT) compared to GRAMD1 TKO cells or GRAMD1 TKO cells that stably expressed mutant versions of EGFP-GRAMD1b [R189W, R189W/R191A (RW/RA)] (mean ± SEM, n = 3 independent experiments for each condition).",
    "ncbi_link": "EGFP: 
GRAMD1b: 57476
GRAMD1: 54762///57655///57476
GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(B) Quantification of the ratio of PM signals to the cytosolic signals of wild-type EGFP-GRAM1b (WT) and mutant versions of EGFP-GRAM1b (R166L, Q173I, F182I, T184V, F186L, G187L, A188S), as assessed by confocal microscopy and line scan analysis from GRAMD1 TKO HeLa cells, expressing indicated constructs, as shown in (C) and Fig EV4A (mean ± SEM, n = 10 cells for each condition; data are pooled from one experiment; Dunnett's multiple comparisons test, **P < 0.0001).",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(D) Confocal images of live wild-type (control) and GRAMD1 TKO HeLa cells, expressing either wild-type EGFP-GRAM1b (WT) or mutant EGFP-GRAM1b (G187L), with or without SMase treatment (100 mU/ml for 1 hour at 37°C). Insets show at higher magnification the regions indicated by white dashed boxes. Note the recruitment of mutant EGFP-GRAM1b (G187L) to the PM even in wild-type HeLa cells at rest, which was further enhanced by SMase treatment. Scale bars, 10 µm.",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(E) Quantification of the ratio of PM signals to the cytosolic signals of wild-type EGFP-GRAM1b (WT) and mutant EGFP-GRAM1b (G187L), as assessed by confocal microscopy and line scan analysis from GRAMD1 TKO HeLa cells, expressing indicated constructs, with or without SMase treatment (100 mU/ml for 1 hour at 37°C), as shown in (D) (mean ± SEM, n = 10 cells for each condition; data are pooled from one experiment).",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(F) A confocal image of live GRAMD1 TKO HeLa cells expressing mutant EGFP-GRAM1b (G187L). Cells were cultured in the medium supplemented with 10% lipoprotein deficient serum (LPDS) and mevastatin (50 µM) for 16 hours to deplete accessible cholesterol before imaging. An inset shows at higher magnification the region indicated by a white dashed box. Note the absence of PM recruitment (compare to (D)). Scale bars, 10 µm.",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(G) Time course of normalized EGFP signal, as assessed by TIRF microscopy, from GRAMD1 TKO (TKO) HeLa cells expressing either wild-type EGFP-GRAM1b (WT) or mutant EGFP-GRAM1b (G187L) as indicated. Cells were cultured in the medium supplemented with 10% lipoprotein deficient serum (LPDS) and mevastatin (50 µM) for 16 hours before imaging. SMase treatment (100 mU/ml) is indicated. Right: Values of ΔF/F0 corresponding to the end of the experiment as indicated by the arrow [mean ± SEM, n = 36 cells (WT), n = 37 cells (G187L), data are pooled from two independent experiments for each condition; two-tailed unpaired Student's t-test, **P = 0.0003]. Note the rapid PM recruitment of G187L mutant compared to WT.",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(A) Effects of mutation of G187 on the property of the GRAM domain of GRAMD1b (GRAM1b) to sense transient expansion of the accessible pool of PM cholesterol. Indicated EGFP-tagged mutant versions of GRAM1b were expressed in GRAMD1 TKO HeLa cells and imaged under confocal microscopy with or without SMase treatment (100 mU/ml for 1 hour at 37°C) or with SMase treatment followed by 5 min treatment with Methyl-β-cyclodextrin (MCD) (5 mM) to assess their PM recruitment. The mean values (n = 20 cells from two independent experiments for untreated and SMase-treated conditions; n = 10 cells from one experiment for SMase & MCD-treated conditions) of the ratio of PM signals to the cytosolic signals, as assessed by line scan analysis, are presented for each condition as a heatmap. Amino acids are ranked according to Goldman, Engelman and Steitz (GES) hydrophobicity scale with the most hydrophobic amino acid on the top.",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "(D) Confocal images of live GRAMD1 TKO HeLa cells that stably expressed either EGFP control or EGFP-GRAMD1b constructs as indicated. Cells were stained with recombinant mCherry-D4H proteins (10 mg/ml) (accessible PM cholesterol biosensor) for 15 min at room temperature before imaging. Insets show at higher magnification the regions indicated by white dashed boxes. Note that expression of EGFP-GRAMD1b-WT, but not EGFP-GRAMD1b-R189W, reduced binding of mCherry-D4H to the PM, in GRAMD1 TKO HeLa cells. Further reduction in mCherry-D4H binding to the PM was observed in GRAMD1 TKO HeLa cells that stably expressed EGFP-GRAMD1b-G187L compared to GRAMD1 TKO HeLa cells that stably expressed EGFP-GRAMD1b-WT. Scale bars, 10 µm. (E) Values of mCherry-D4H signals at the PM after background subtraction, as assessed by confocal microscopy and line scan analysis of GRAMD1 TKO HeLa cells that stably expressed either EGFP or indicated EGFP-GRAMD1b constructs as shown in (D) [mean ± SEM, n = 30 cells for all the conditions; data are pooled from three independent experiments; Dunnett's multiple comparisons test, **P < 0.0001].",
    "ncbi_link": "GRAMD1: 54762///57476///57655"
  },
  {
    "caption": "Top: Schematic of primer pairs designed to discriminate between wild-type and knock-in alleles. Bottom: Representative genotyping of Ccnd1+/+, Ccnd1+/KI, and Ccnd1KI/KI mice validating specificity of the primer pairs and somatic insertion of the targeting construct.",
    "ncbi_link": "Ccnd1: 595
Ccnd1: 12443"
  },
  {
    "caption": "PCR analysis of transcript b expression in organs harvested from Ccnd1+/+ and Ccnd1KI/KI mice, demonstrating production of transcript b specifically in KI mice. Gapdh serves as a control (NTC, Non-template control).",
    "ncbi_link": "Gapdh: 
Ccnd1: 12443
Ccnd1: 595"
  },
  {
    "caption": "Immunoblot from parallel samples in (C) utilizing antisera specific to the 33 amino acids generated by human CCND1 intron 4. Lamin B serves as a control. Arrow indicates the cyclin D1b band.",
    "ncbi_link": "cyclin D1: 595"
  },
  {
    "caption": "Neonates from 2 independent litters of Ccnd1+/KI × Ccnd1+/KI crosses were sacrificed at birth and genotyped. Mice were organized by genotype and total size measured.Mass of neonates was calculated at birth and average mass quantified (n = at least 4 mice per group).Mice were weighed weekly, and growth is plotted as the average mass of each genotype/week (left: male, right: female, n > 5 per gender and genotype).",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "Mice were held by the tails and analyzed for the leg clasping phenotype. Representative images of Ccnd1+/+ and Ccnd1KI/KI age-matched mice are shown (n > 10 for each group).",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "Top: Individual whole-cell lysates were generated from the eyes of mice of each genotype and analyzed for expression of +/+ cyclin D1 (cyclin D1a) and KI/KI cyclin D1b via immunoblot using antisera specific to each isoform. Bottom: Representative H&E staining of retinal tissue from Ccnd1+/+ and Ccnd1KI/KI mice showing individual layers of the retina. The ganglion cell layer and inner plexiform layer (G + IPL), inner nuclear layer (INL), and outer nuclear layer (ONL) were quantified (right). Images were taken at 400× magnification.",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "Indicated passage-matched MAF lines were grown to 70% confluency and then harvested for RNA and protein extraction. Top: qPCR analysis of cyclin D1 transcript using primer pairs common to both transcript a and transcript b. Bottom: Immunoblot of cyclin D1 levels in Ccnd1+/+ and Ccnd1KI/KMAF lines using an antibody common to both isoforms.",
    "ncbi_link": "Ccnd1: 595
cyclin D1: 595"
  },
  {
    "caption": "Ccnd1+/+ or Ccnd1KI/KI MAF lines were stably transfected with either cyclin D1a (+/+), cyclin D1b (KI/KI) or vector control constructs. After selection with puromycin, individual lines were assessed for the induction of cyclin D1a in the +/+ line and cyclin D1b in KI/KI lines via immunoblot.",
    "ncbi_link": "Ccnd1: 12443
Ccnd1: 595"
  },
  {
    "caption": "Passage-matched Ccnd1+/+ or Ccnd1KI/KI MAF lines were infected with lentivirus containing vector control or h-Ras constructs. Cells were selected with puromycin for 14 days and assayed for β-galactosidase activity. DAPI serves as a control for cell number. Images were taken at 200× magnification with insets taken at 400× magnification.",
    "ncbi_link": "Ccnd1: 595
h-Ras: 15461"
  },
  {
    "caption": "The indicated cell lines were grown in complete media and assayed for h-Ras expression via immunoblot. Lamin B serves as a loading control.",
    "ncbi_link": "h-Ras: 15461"
  },
  {
    "caption": "Ccnd1+/+ and Ccnd1KI/KIMAF lines were arrested in G1, S, and G2/M phases of the cell cycle and expression of cyclin D1 isoforms determined by immunoblot. cyclin A2 and cyclin B1 serve as phase-specific cell cycle controls.",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "Ccnd1+/+ and Ccnd1KI/KI MAF lines were transfected with a validated pool of siRNA directed against the N-terminus of the murine cyclin D1 transcript or control siRNA in full serum. 48 h post-transfection cells were harvested and analyzed for biochemical markers of cell cycle kinetics via immunoblot. GAPDH and Lamin B serve as controls.",
    "ncbi_link": "Ccnd1: 12443
Ccnd1: 595"
  },
  {
    "caption": "Ccnd1+/+ and Ccnd1KI/KI cells were transfected with a pool of siRNA directed against the N-terminus of the murine cyclin D1 transcript or scramble control for 48 h (as in Figure5). Cells were then fixed and stained for markers of double-strand breaks (p-H2AX and 53BP1, 400× objective). Total number of foci for each cell was quantified and represented as the % of cells with > 10 foci/cell (p-H2AX) or % of cells with > 2 foci/cell (53BP1). Error bars represent ± SEM.",
    "ncbi_link": "Ccnd1: 595
cyclin D1: 12443"
  },
  {
    "caption": "Ccnd1+/+ and Ccnd1KI/KIMAF lines were grown in serum-proficient media for 24 h and probed for expression of auto-modified PARP1 via immunoblot. Gapdh and cyclin D1b serve as controls.",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "Indicated MAF lines were treated as in (A) and harvested 48 h post-transfection. Cells were analyzed for total PAR levels via immunoblot. cyclin D1 levels serve as siRNA validation controls.",
    "ncbi_link": "cyclin D1: 12443"
  },
  {
    "caption": "cyclin D1b expression was induced in the prostate cancer cell line LNCaP (previously described (Augello et al, 2014)) and stained for p-H2AX and 53BP1 foci as in (A) via immunofluorescence (400× objective). Total number of foci/cell is reported for LNCaP vector control and cyclin D1b-expressing isogenic pairs in biological triplicate.",
    "ncbi_link": "cyclin D1: 595"
  },
  {
    "caption": "Ccnd1+/+ and Ccnd1KI/KIMAF lines were grown in serum-proficient media for 24 h. Cells were then treated with control DMSO or 2.5 μM of the PARP inhibitor ABT-888. One hour post-treatment, the indicated lines were treated with 5 Gy of radiation. Cells were then allowed to recover for 48 h, after which BrdU was added for 1 h, and then harvested for bivariate flow cytometry. Representative traces for each condition are shown (left) and BrdU incorporation of biological triplicates was quantified (right).",
    "ncbi_link": "Ccnd1: 595"
  },
  {
    "caption": "(B) Comparison of the turbidimetric assay results obtained with mpn142 and mpn142Opt secretion signals. Culture supernatants (n=1) were collected at 0 h, 5 h or 24 h post-inoculation as indicated. WT strain and medium (Hayflick) were added as controls.",
    "ncbi_link": "mpn142: "
  },
  {
    "caption": "(A, B) Mature S. aureus biofilms were allowed to develop for 24 h in polystyrene plates and then treated for the indicated time intervals with cell suspensions, or culture supernatants of the CV2 or the CV2-DispB strains (A) or the WT or the WT-DispB strain (B). Biofilm presence was assessed by crystal violet staining and included a negative staining control (i.e., crystal violet without biofilm). The results are expressed as mean ± s.d. of OD 595 nm absorbance values obtained from three different biological replicates (n=3) and statistically compared by one-sided ANOVA followed by the post-hoc Fisher's PLSD test: *P ≤ 0.05; **P ≤ 0.005; ***P ≤ 0.0005; ****P ≤ 0.00005",
    "ncbi_link": "DispB: "
  },
  {
    "caption": "(C, D) Plots showing results obtained from the in vitro or ex vivo dispersion assays with the indicated strains and from the staining control. Each circle represents the OD 595 nm values obtained for individual catheters (n≥4), whereas mean ± s.d. is represented with lines inside each group. Results from one-sided ANOVA followed by Fisher's PLSD test are shown for treatments statistically different from those based on strains not secreting dispersin B (i.e., the WT or CV2 strains). *P ≤ 0.05; **P ≤ 0.005; ***P ≤ 0.0005.",
    "ncbi_link": "dispersin B: "
  },
  {
    "caption": "B, C) (B) Colocalization of PD-L1 and  GFAP in AD and (C) in control patients (MX-O4 = amyloid deposits, upper picture: bar = 100 µm, lower picture: bar=30 µm). D) Immunohistochemical  detection of PD-L1 in 9-month-old female APP/PS1 mice (bar = 50 µM). E) Immunohistochemical  detection of PD-L1 in 4-month-old female  APP/PS1 mice  (bar = 20 µm). ",
    "ncbi_link": "APP: 11820
PS1: 19164"
  },
  {
    "caption": "A) C6 cells expressing PD-L1-myc treated with the  γ-secretase  inhibitor DAPT for 18 h. PD-L1 was detected using a myc-antibody.",
    "ncbi_link": "myc: 
PD-L1: 60533"
  },
  {
    "caption": "B) Immunoblot of HEK293 cells expressing PD-L1-myc and presenilin 1 (hPS1) or a  presenilin 1 dominant negative mutant (hPS1 D246A).",
    "ncbi_link": "hPS1: 5663
presenilin 1: 5663"
  },
  {
    "caption": "D) 18 h 1 μM PMA  treatment of C6  cells expressing PD-L1-myc. Secretion of PD-L1 in the conditioned medium (CM) was detected using antibody AF1019.",
    "ncbi_link": "myc: 
PD-L1: 60533"
  },
  {
    "caption": "A) Colocalization of PD-1 and CD11b (MX-04=methoxy-XO4, stains amyloid  deposits) in AD by  immunohistochemistry (bar=50 µm). B) Colocalization of PD-1 and Iba1 or PD-1 and  Aβ in a female APP/PS1 mouse at 9 months of age by  immunohistochemistry (bar=20 µm). ",
    "ncbi_link": "APP: 11820
PS1: 19164"
  },
  {
    "caption": "E) ELISA analysis of TNFα secretion by wild type (wt) and PD-1-/- microglia induced by 0.5 µM Aβ1-42 for 6 h in vitro (n=3 biological replicates, one-way ANOVA (DF = 1, F = 8.29, p= 0.021), Tukey's HSD, * p<0.05). Data information: central bands represent median, boxes show interquartile range (IQR) and whiskers define the +/-1.5xIQR.",
    "ncbi_link": "PD-1: 18566"
  },
  {
    "caption": "F-H) Microglia from methoxy-XO4-injected, 8-month-old female, wild type (wt) and APP/PS1 mice  were analyzed (F) for PD-1 (n=5 biological replicates per group, one-way ANOVA (DF = 2, F = 13.99, p=0.0013), Tukey's HSD, ** p<0.01), (G) for CD11b (n=5 biological replicates per group, one- way ANOVA (DF = 2, F = 30.06, p=5.47x10-05), Tukey's HSD, *** p<0.001) and (H) CD45 by flow cytometry (n=5 biological replicates per group, one-way ANOVA (DF = 1, F = 24.96, p=0.00013), Tukey's HSD, *** p<0.001) and normalized to the expression of wild type  mice (represented by dashed lines). Data information: central bands represent median, boxes show interquartile range (IQR) and whiskers define the +/-1.5xIQR.",
    "ncbi_link": "APP: 11820
PS1: 19164"
  },
  {
    "caption": "A, B)  ELISA of the (A) RIPA soluble fraction of female APP/PS1 and APP/PS1 PD-1-/- mice for  Aβx-40 (biological replicates with n=6 for APP/PS1  and n=5 for APP/PS1 PD-1-/-, mean+/-SEM, one-way ANOVA (DF = 1, F = 0.6, p=0.45), Tukey's HSD, ** p<0.01, *** p<0.001) and (B) of the SDS soluble fraction  (biological replicates with n=6 for APP/PS1 and n=5 for APP/PS1 PD-1-/-, mean+/-SEM, one-way ANOVA(DF=1, F= 32.8, p=2x10-5), Tukey's HSD, ** p<0.01, *** p<0.001).",
    "ncbi_link": "APP: 11820
PD-1: 18566
PS1: 19164"
  },
  {
    "caption": "D, E)  Mice were analyzed for (D) percentage of the covered areas (5 sections per  mouse analyzed with the mean representing an individual data point; biological replicates with n=6 for APP/PS1 and n=9 for  APP/PS1 PD-1-/-, mean +/-SEM, one-way ANOVA (DF=1, F=0.905, p=0.90), Tukey's HSD, ** p<0.01, *** p<0.001) and (E) the number of  plaques per mm2 (5 sections per mouse  analyzed with the mean representing an individual data point; biological replicates with n=6 for  APP/PS1 and n=9 for  APP/PS1 PD-1-/-, mean +/-SEM, one-way ANOVA (DF=1, F=4.08, p=0.054), Tukey's HSD, ** p<0.01, *** p<0.001).",
    "ncbi_link": "APP: 11820
PD-1: 18566
PS1: 19164"
  },
  {
    "caption": "G) Time needed to reach the hidden platform (latency in seconds) in the  Morris water maze test (mean +/-SEM of biological replicates with n=12 for wt, n=5 for PD-1-/-, n=7 for APP/PS1, and n=8 for APP/PS1 PD-1-/-, one-way ANOVA (DF=3, F=17.72, p=1x10-9), Tukey's HSD, * p<0.05, *** p<0.001).",
    "ncbi_link": "APP: 11820
PD-1: 18566
PS1: 19164"
  },
  {
    "caption": "A) In vitro phagocytosis of  FAM-Aβ1-42 by wild type or PD-1-/- microglia  for up to 6 h (mean +/-SEM of a technical quadruplicate, Student's t-test, ** p<0.01, *** p<0.001, representative result of an n=2 biological replicate). B) In vitro phagocytosis  of FAM-Aβ1-42 by wild type  microglia cultured in astrocyte-conditioned medium (ACM) from wild type or PD-L1-/- astroglial cultures (mean +/-SEM of a technical quadruplicate, Student's t-test, * p<0.05, *** p<0.001, representative result of an n=2 biological replicate) ",
    "ncbi_link": "PD-L1: 60533
PD-1: 18566"
  },
  {
    "caption": "D) Quantification of microglial in vivo phagocytosis  in female  APP/PS1  and APP/PS1 PD-1-/- mice at 8.5 month of age after intraperitoneal injection of methoxy-XO4 (biological replicates with n=5 for APP/PS1 and n=4 for APP/PS1 PD-1-/- mice, Student's t-test (t = 2.1808, df = 6.9829), * p<0.05). Data information: central bands represent median, boxes show interquartile range (IQR) and whiskers define the +/-1.5xIQR.",
    "ncbi_link": "APP: 11820
PD-1: 18566
PS1: 19164"
  },
  {
    "caption": "E-G) Relative expression of the cell surface marker (E) CD36 (biological replicates with n=5 for APP/PS1 and n=4 for APP/PS1 PD-1-/- mice, ANOVA (DF=1, F= 0.002, p=0.94), Tukey's HSD, * p<0.05, *** p<0.001), (F) CD11b (biological replicates with n=5 for APP/PS1 and n=4 for APP/PS1 PD-1-/- mice) and (G) CD45 on methoxy-XO4+ versus methoxy-XO4- microglia in APP/PS1  and APP/PS1 PD-1-/- mice normalized to methoxy-X04-negative cells from  APP/PS1 mice (biological replicates with n=5 for  APP/PS1 and n=4 for APP/PS1 PD-1-/- mice) Data information: central bands represent median, boxes show interquartile range (IQR) and whiskers define the +/-1.5xIQR.",
    "ncbi_link": "APP: 11820
PD-1: 18566
PS1: 19164"
  },
  {
    "caption": "B) Different expression of inflammasome-related genes (abs(fold change) > 1.5, p < 0.05, Benjamini- Hochberg adjusted) in PD-1-/- vs. wild type microglia. C) Different expression of complement system-related genes (abs(fold change) > 1.5, p < 0.05, Benjamini-Hochberg adjusted) in PD-1-/- vs. wild type microglia. ",
    "ncbi_link": "PD-1: 18566"
  },
  {
    "caption": "(F) Volcano plot showing the expression levels of BRAFi-resistant genes (identified in 501Mel by CRISPR-SAM screen) in 12 human melanoma cell lines. The fold change corresponds to the ratio of expression levels found in resistant and sensitive cell lines. In red: selected genes. EGFR is considered as positive control and SMAD3, BIRC3 and SLC9A5; selected as favorite genes for the next steps. SMAD3, BIRC3, SLC9A5 and AFAP1 are BRAFi-resistance genes and potent tumor-promoting genes (BRAFi for PBV",
    "ncbi_link": "AFAP1: 60312
BIRC3: 330
EGFR: 1956
SLC9A5: 6553
SMAD3: 4088"
  },
  {
    "caption": "(G) SMAD3 depletion (siRNA#1 & #2) decreased cell density and increased BRAFi effect (vemurafenib) on BRAFi-resistant cells (SKMel28R). CTR for non-targeting siRNA. DMSO for dimethylsulfoxide (solvent of vemurafenib; BRAFi). n=3 biologically independent experiments. Each histogram represents the mean + s.d. (H) SMAD3 depletion (siRNA#1 & #2) decreased cell density and increased BRAFi effect (vemurafenib, BRAFi) on BRAFi-resistant cells (Me1402). CTR for non-targeting siRNA. DMSO for dimethylsulfoxide (solvent of vemurafenib). n=3 biologically independent experiments. Each histogram represents the mean + s.d.",
    "ncbi_link": "SMAD3: 4088"
  },
  {
    "caption": "(B) AhR activation by exogenous and endogenous ligands promotes SMAD3 induction. 501Mel cells AhR wild-type or knock-out have been exposed to exogenous and endogenous AhR ligands; TCDD (5nM) or ITE (10µM) or the solvent (DMSO) during 10 days. n=5 biologically independent experiments for AhR WT cells and n=3 for AhR KO cells. Each histogram represents the mean + s.d. (C) AhR activation by exogenous and endogenous AhR ligands promotes TIPARP induction. 501Mel cells have been treated as described in B. n=5 biologically independent experiments for AhR WT cells and n=3 for AhR KO cells. Each histogram represents the mean + s.d.;",
    "ncbi_link": "AhR: 196
SMAD3: 4088
TIPARP: 25976"
  },
  {
    "caption": "(E) Loss of AhR reduces SMAD3 expression levels. SMAD3 expression has been investigated in SKMel28 cells AhR wild-type (WT) or knock-out (KO). SKMel28R, have been obtained from SKMel28S by chronic exposure to non-lethal doses of BRAFi R for BRAFi-resistant SKMel28 cells and S for sensitive.",
    "ncbi_link": "AhR: 196
SMAD3: 4088"
  },
  {
    "caption": "(E) Heatmap depicting mRNA levels of SMAD3-signature in BRAF(V600E) non-treated melanoma patients (dataset from TCGA; SKCM, BRAF(V600E) mutated: n=118). Three pigmentation genes (MITF, MLANA and TYR) have been added to highlight the differentiation states of tumors. ~20% of tumors are considered as dedifferentiated tumors (red box) with a high SMAD3-signature.",
    "ncbi_link": "BRAF: 673
MITF: 4286
MLANA: 2315
SMAD3: 4088
TYR: 7299"
  },
  {
    "caption": "(H) SMAD3 depletion decreases expression of SMAD3-regulated genes. SMAD3 knock-down by siRNA decreased mRNA expression of BRAFi-resistance genes in SKMel28R and Me1402. NRP1 mRNA was not detected in our experimental conditions.",
    "ncbi_link": "NRP1: 8829
SMAD3: 4088"
  },
  {
    "caption": "(a) Relative quantification (RQ) of CG7630 transcript after RNAi with a 120-bp inverted-repeat sequence (act5c-gal4>UAS-CG7630RNAi) compared to control (act5c-gal4>+).",
    "ncbi_link": "act5c: 31521
CG7630: 50266
gal4: 855828"
  },
  {
    "caption": "(b) Relative percentage of egg to adult viability of CG7630 RNAi cross (act5c-gal4/CyO.GFP x UAS-CG7630RNAi) and control cross (act5c-gal4/CyO.GFP x w1118), calculated at three developmental stages (eggs, pupae and adults), (n > 250, Chi-square test 9.920 df(2), **p = 0.007).",
    "ncbi_link": "GFP: 
act5c: 31521
CG7630: 50266
gal4: 855828
CyO: 34350"
  },
  {
    "caption": "(d) Kinetic enzyme activity of individual MRC complexes in CG7630 RNAi and control individuals normalized by citrate synthase (CS) activity.",
    "ncbi_link": "CG7630: 50266"
  },
  {
    "caption": "(e) In gel-activity assays for MRC complexes II and IV in DDM-solubilized mitochondria from RNAi (act5c-gal4>UAS-CG7630RNAi) and control larvae (act5c-gal4>+).",
    "ncbi_link": "act5c: 31521
CG7630: 50266
gal4: 855828"
  },
  {
    "caption": "(f) BN-PAGE, Western blot immunodetection of MRC complexes from CG7630 RNAi (act5c-gal4>UAS-CG7630RNAi) and control (act5c-gal4>+) larvae using antibodies against specific subunits: anti-UQCRC2 (complex III), anti-NDUFS3 (complex I), anti-COX4 (complex IV) and anti-SDHA (complex II).",
    "ncbi_link": "act5c: 31521
CG7630: 50266
gal4: 855828"
  },
  {
    "caption": "(g) Western blot analysis of steady state levels (SDS-PAGE) of MRC subunits COX4 (complex IV), SDHA (complex II) and UQCR-C2 (complex III) in whole lysates from CG7630 RNAi (act5c-gal4>UAS-CG7630RNAi) and control (act5c-gal4>+) larvae.",
    "ncbi_link": "act5c: 31521
CG7630: 50266
gal4: 855828"
  },
  {
    "caption": "(h) Western blot analysis of anti-HA affinity purified samples from S2R+ D. melanogaster cells. EV = samples from cells carrying the empty expression vector. CG7630-HA = samples from cells expressing HA-tagged CG7630. Tot = total mitochondrial-enriched fractions; unb = unbound material; IP:HA = immunoprecipitated material. Samples were probed with antibodies against MRC subunits of complexes I (NDUFS3), II (SDHA), III (UQCR-C2), IV (COX4) and V (ATP5A).",
    "ncbi_link": "HA: 
CG7630: 50266"
  },
  {
    "caption": "(a) Relative quantification (RQ) of CG7630 transcript in wild-type D. melanogaster S2R+ cells treated with a dsRNA targeting CG7630 (CG7630 KD) and a mock control dsRNA (mock).",
    "ncbi_link": "CG7630: 50266"
  },
  {
    "caption": "(b) Relative quantification (RQ) of CG7630 and COX7B transcripts in stable S2R+ cell lines carrying the empty expression vector (EV:GFP;neo), and expression vectors carrying HA-tagged forms of human COX7B (hCOX7B-HA;neo) and CG7630 (CG7630-HA;neo). Cells were treated with a dsRNA targeting CG7630 (striped bars, CG7630 KD) and a mock control dsRNA (solid bars, mock). N/D = not detected.",
    "ncbi_link": "GFP: 
HA: 
CG7630: 50266
COX7B: 1349"
  },
  {
    "caption": "(c) Immunoblot analysis of stable S2R+ cell lines carrying the empty expression vector (EV:GFP;neo), and expression vectors carrying HA-tagged forms of human COX7B (hCOX7B-HA;neo) and CG7630 (CG7630-HA;neo). The CG7630 transcript was knocked-down (KD) in cells by a dsRNA targeting CG7630 and compared with cells treated with a mock control dsRNA (mock). Samples were probed with an antibody anti HA tag and with an antibody against Hsp70 as an endogenous control.",
    "ncbi_link": "GFP: 
HA: 
CG7630: 50266
COX7B: 1349"
  },
  {
    "caption": "(d) Kinetic enzyme activity of COX normalized by citrate synthase activity (CS) in stable S2R+ cell lines carrying the empty expression vector (EV:GFP;neo), and expression vectors carrying HA-tagged forms of human COX7B (hCOX7B-HA;neo) and CG7630 (CG7630-HA;neo). Cells were treated with a dsRNA targeting CG7630 (striped bars, CG7630 KD) and a mock control dsRNA (solid bars, mock).",
    "ncbi_link": "GFP: 
HA: 
CG7630: 50266
COX7B: 1349"
  },
  {
    "caption": "A Ccno mRNA is expressed in the embryonic node at E8 as shown by in situ hybridization. Occasionally, additional expression is observed at the posterior tip of the embryo (asterisk). Double labelling by staining for LacZ expression from the CcnoTA allele (shown in B) and in situ hybridization for Dand5, marking crown cells at the circumference of the node. Ccno expression is restricted to ciliated, ventral pit cells of the node as detailed in the transverse section at the indicated plane.",
    "ncbi_link": "LacZ: 
Ccno: 218630
Dand5: 23863"
  },
  {
    "caption": "C Whole embryo X‐Gal staining of E16 CcnoTA/+ and wild‐type control embryos and indicated section planes of (D-F').",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "D-F' Histological sections of LacZ‐stained CcnoTA/+ embryo at E16 reveal Ccno expression in the epithelium of (D) plexus choroideus and ependyme, (E) snout epithelium, and (F, F') trachea and bronchi. pc, plexus choroideus; se, snout epithelium; tr, trachea; and br, bronchus.",
    "ncbi_link": "LacZ: 
Ccno: 218630"
  },
  {
    "caption": "A Ccno‐deficient mice develop severe hydrocephalus resulting in characteristic head deformation at P21 (arrow).",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "F, F' Scanning electron microscopy (SEM) of P21 adult trachea shows reduced numbers of cilia of Ccno‐deficient MCCs. Remaining cilia are found in the central regions of the cell surface, and cell margins frequently lack the ciliary decoration (arrows).",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "G Transmission electron microscopy (TEM) of wild‐type and CcnoRA/RA MCCs from adult trachea. Ccno‐deficient MCCs show reduced numbers of basal bodies and cilia that correctly docked to the apical cell surface (arrows). Ectopic electron‐dense material is found within the cytoplasm of Ccno‐deficient MCCs (arrowheads).",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "A-H X‐Gal‐staining of (A-C) control and (D-H) CcnoTA/+ embryonic lungs at indicated stages showing onset of Ccno expression from E13 in the proximal trachea and in the main bronchi. Expression is extending to more distal regions, and from E16 staining is also found in bronchioli.I X‐Gal‐staining indicating LacZ expression from the CcnoTA/+ allele in mTEC cultures after 5 days of differentiation‐onset by switching to air-liquid interface (ALI) conditions (ALI d5).",
    "ncbi_link": "LacZ: 
Ccno: 218630"
  },
  {
    "caption": "J Transcript levels of Ccno and indicated genes with known functions for the generation of multiple cilia during mTEC differentiation. mRNA levels from three independent experiments were measured by qRT-PCR and levels of expression set as 1 on day 0 of ALI cultures. Scales for Ccno and Deup1 are indicated on the left, and for Cep152, Cep63 and Ift57 on the right side.",
    "ncbi_link": "Deup1: 234964
Ccno: 218630
Cep152: 99100
Cep63: 28135
Ift57: 73916"
  },
  {
    "caption": "K Relative mRNA expression levels for indicated genes were measured by qRT-PCR in wild‐type and Ccno‐deficient mTEC cultures at indicated days after differentiation‐onset. Relative values were calculated as in (J) relative to day 0 of ALI cultures.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "A-B' SEM of tracheae from (A, A') wild‐type and (B, B') CcnoRA/RA embryos at E17. In comparison to wild‐type MCCs, Ccno‐deficient MCCs almost completely lack formation of multiple cilia and only single, or doublet (arrow) cilia are observed at E17.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "C-E The lack of multiple cilia at E17 stages is reflected by the almost complete absence of acetylated α‐tubulin staining as marker for axonemes in (D) Ccno‐deficient MCCs of E17 embryonic trachea as quantified in (E). FOV, field of view.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "F-I TEM of MCCs from E17 embryonic tracheae shows deuterosomes with forming procentrioles in (F, F', H) Ccno‐proficient and (G, G', I) Ccno‐deficient MCCs. Asterisks in (F, G) indicate microvilli that extend from the apical cell surface. (F', G') Deuterosomes in Ccno‐deficient MCCs are significantly enlarged (identical size bars in F' and G') and show irregular morphology, which is different to the annular shape of wild‐type deuterosomes as seen in (F', H). Procentrioles (arrowheads in F' and I) that are found at deuterosomes of (I) Ccno‐deficient MCCs were recurrently found being shorter and appeared less structured in comparison to (F', H) wild‐type cells.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "J The average length of procentrioles was quantified for wild‐type and Ccno‐deficient MCCs of E17 tracheae (49 procentrioles in n = 3 independent samples for wild‐types and 47 procentrioles in n = 3 independent samples for Ccno‐deficient MCCs).K The diameter of deuterosomes (41 deuterosomes in n = 3 independent samples for wild‐types; 38 deuterosomes in n = 5 independent samples for Ccno‐deficient MCCs) was measured in wild‐type and Ccno‐deficient MCCs of E17 tracheae.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "Double IF analysis of mTEC cultures at early stage of MCC differentiation and centriole amplification (ALI day 3) using antibodies for the deuterosome protein DEUP1 and the early centriole marker SAS‐6. Deuterosome numbers are decreased and deuterosome size enlarged in Ccno‐deficient MCCs as quantified in (C). Deuterosome‐dependent centriole biogenesis is severely reduced in Ccno‐deficient MCCs as shown by reduced staining for the early centriole marker SAS‐6.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "IFstaining for DEUP1 reveals a further size increase of deuterosomes of Ccno‐deficient MCCs at later stages of centriole biogenesis (ALI day 7). Deuterosome number and size were quantified in (C). IF using a Centrin antibody shows globally reduced presence of centrioles at ALI day 7, which stay localized below the level of deuterosomes and fail to dock to the apical cellmembrane in Ccno‐deficient MCCs as seen in z‐projection.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "IFstaining for DEUP1 in (A, B) was analysed by Imaris 7.7.2 software to calculate average deuterosome number of wild‐type (n = 17) and Ccno‐deficient (n = 19) MCCs at ALI day 3, and wild‐type (n = 12) and Ccno‐deficient (n = 14) MCCs at ALI day 7. Deuterosome size was measured using the spot measurement tool in n = 10 MCCs for both genotypes at ALI day 3, and in wild‐type (n = 12) and Ccno‐deficient (n = 14) MCCs at ALI day 7.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "A, B IF analysis of mTEC cultures at ALI day 7 using antibodies against the centriole marker Centrin and CEP164, which marks maturing centrioles. At ALI day 7, centrioles of wild‐type MCCs are decorated with CEP164 and are mostly localized to the apical cellmembrane. The fewer centrioles of Ccno‐deficient MCCs do not colocalize with CEP164 and fail to reach the apical cell surface as seen in z‐projection. Lack of CEP164 indicates immature centrioles in Ccno‐deficient MCCs. (B) Total centriole numbers per MCC were counted in n = 11 MCCs for both genotypes using Imaris 7.7.2 software.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "C, D Double IFstaining using Centrin‐ and CP110‐specific antibodies shows an almost complete absence of CP110 from Centrin‐positive centrioles in the majority of wild‐type MCCs at day 7 of ALI cultures. Most Ccno‐deficient MCCs exhibit pronounced CP110 staining that colocalizes with Centrin as seen in z‐projection. (D) CP110‐positive MCCs were counted in wild‐type and Ccno‐deficient MTEC cultures and the percentages of CP110‐positive MCCs from total MCCs calculated.",
    "ncbi_link": "Ccno: 218630"
  },
  {
    "caption": "(A) BMDMs were infected with L. pneumophila JR32 or the legA9 mutant with MOI of 0.5. CFUs were scored at 1, 24, 48, and 72 h. (B) BMDMs were infected with JR32 or the legA9 mutant harboring empty PL, or legA9+ legA9 pBC‐KS+ PL. (A, B) Data are presented as means ± SD of at least three independent experiments. Asterisks indicate significant differences, (*p < 0.05, **p < 0.01, ***p < 0.001; two‐tailed t‐test).",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "Four female C57BL/6 mice/group received 1 × 106 of JR32 or legA9 mutant bacteria intratracheally. Lungs were homogenized and plated for CFUs counting at (C) 4 or (D) 48 h postinfection. (C, D) Data are shown as mean + SD of n = 4 and are representative as one of two independent experiments. Asterisks indicate significant differences (**p < 0.01 two‐tailed t‐test)",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "(A) Representative images from 6 h infected WT BMDMs with JR32 or legA9 mutant bacteria. Nuclei were stained blue with DAPI and L. pneumophila stained green with L. pneumophila antibody. Lyso−tracker red was used to stain acidified lysosomes. White arrows show L. pneumophila colocalization with lysotracker.",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "(C) Representative images from 6 h infected WT BMDMs with JR32 or legA9 mutant bacteria. LC3 is stained red with LC3 antibody. White arrows show L. pneumophila colocalization with LC3.",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "Induction of autophagy in macrophages restricts legA9 mutant replication, and rescues colocalization with LC3 and fusion with lysosomes. BMDMs were untreated or pretreated with rapamycin (Rap) for 1 h and kept throughout the infection. BMDMs were infected with L. pneumophila JR32 or the leg A9 mutant for (A) 1 or (B) 24 h with an MOI of 0.5. CFUs were scored at these time points.",
    "ncbi_link": "JR32: 
leg A9: 19831968
legA9: 19831968"
  },
  {
    "caption": "(A) BMDMs derived from WT and Atg5−/− mice were infected with L. pneumophila JR32 or legA9 mutant at an MOI of 0.5. Data are shown as mean ± SD of n = 3 and are representative of two independent experiments. Asterisks indicate significant differences (*p < 0.05; two−tailed t−test.",
    "ncbi_link": "JR32: 
Atg5: 11793
legA9: 19831968"
  },
  {
    "caption": "(B) Western blot showing the absence of Atg 5 in the knockout. Data are representative of three independent experiments.",
    "ncbi_link": "Atg 5: 11793"
  },
  {
    "caption": "(A) Representative images from 6 h infected BMDMs with JR32 or legA9 mutant bacteria. Polyubiquitin is stained red. White arrows show L. pneumophila colocalization with polyubiquitin.",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "(A) Representative images from 6 h infected BMDMs with JR32 or legA9 mutant bacteria. P62 is stained red with p62 antibody. White arrows show L. pneumophila colocalization with p62.",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "(C)BMDMs were infected with JR32 or the legA9 mutant for 6 h and the level of p62 protein was quantified in cell lysates by ELISA (performed in triplicate and the SD are too small to detect).",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "BMDMs were nucleofected with scrambled control (sictrl) or siRNA against p62 (sip 62). Twenty‐four hours after nucleofection, murine macrophages were infected with JR32 or legA9 mutant with an MOI of 0.5 for 1 h (D and F) or 24 h (E and G).",
    "ncbi_link": "JR32: 
legA9: 19831968
p62: 18412"
  },
  {
    "caption": "(H) Western blot analysis showing the downregulation of p62 at 24 and 48 h postnucleofection. (A-B and D-H) Data are shown as mean + SD of n = 3 and are representative of three independent experiments. (C) Data are representative of one experiment n = 3. Asterisks indicate significant differences (*p < 0.05, **p < 0.01; two−tailed t−test).",
    "ncbi_link": "p62: 18412"
  },
  {
    "caption": "(A) Caspase−1 KO (casp−1−/−) macrophages were infected with L. pneumophila JR32 or legA9 with an MOI of 0.5 for 1, 24, 48, and 72 h.",
    "ncbi_link": "JR32: 
Caspase−1: 12362
legA9: 19831968"
  },
  {
    "caption": "(B) CFUs were measured at the indicated time points. Levels of IL‐1β were detected in supernatants of WT or casp‐1−/− BMDMs infected with JR32 or the legA9 mutant after 24 h. WT BMDMs were either not treated (NT) or infected with L. pneumophila JR32 or legA9 mutant bacteria for 2 h.",
    "ncbi_link": "JR32: 
casp‐1: 12362
legA9: 19831968"
  },
  {
    "caption": "(A) BMDMs were not infected (NT) or infected with L. pneumophila JR32 or the legA9 mutant at an MOI of 0.5, 1 or 5 for 24 h. Apoptosis was quantified by Photometric enzyme immunoassay analysis of cytoplasmic (apoptosis) histone−associated−DNA fragments (ELISA).",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "(B) BMDMs were either not treated (NT) or treated with L. pneumophila JR32 or the legA9 mutant at an MOI of 0.5 or 5 for 24 h. The fold change in LDH release was measured from the overall population of macrophages. (A-B) Data are shown as mean ± SD of n = 3 and are representative of three independent experiments.",
    "ncbi_link": "JR32: 
legA9: 19831968"
  },
  {
    "caption": "J Comparison of Overall survival (OS) rates for the high-correlation and low-correlation groups, stratified using the EP0_MUC5B (left panel) and EP2_POSTN (right panel) signatures in TCGA. P values are calculated using the log-rank test (N=255).",
    "ncbi_link": "MUC5B: 727897
POSTN: 10631"
  },
  {
    "caption": "G Comparison of Overall survival (OS) rates for the high-correlation and low-correlation groups, stratified using the Macro_C1QC (upper panel), and Mast_CPA3 (lower panel) signatures in TCGA (N=255). P values are calculated using the log-rank test.",
    "ncbi_link": "C1QC: 714
CPA3: 1359"
  },
  {
    "caption": "Sections of K14CreER:H2B-mCherry mice at P4. Scale bar: 100 μm. (Bottom) Quantification of mCherry-positive cells (n=3).. The data from individual mice are connected by lines. Student's t-test. NS, no significance. Whole-mount imaging of K14CreER:R26R-confetti samples at P4. Scale bar: 200 μm. Sections of Lrig1CreER:H2B-mCherry mouse skin at P4. Scale bar: 100 μm. (Bottom) Quantification of mCherry-positive cells (n=3). The data from individual mice are connected by lines. *0.01 test. Whole-mount imaging of Lrig1CreER:R26R-confetti mouse samples at P4. Scale bar: 200 μm. ",
    "ncbi_link": "mCherry: 
Cre: 2777477
ER: 13982
H2B: 319177
K14: 16664
Lrig1: 16206"
  },
  {
    "caption": "H&E (P2, left), ITGA6 (P2, middle) and LOR staining (P4, right) of Col17a1-/- mice (top) and littermate controls (bottom) . The regenerated epidermis is indicated by arrowheads. Scale bar: 200 μm.",
    "ncbi_link": "Col17a1: 12821"
  },
  {
    "caption": "BrdU labeling of Col17a1-/- skin at P2. Scale bar: 100 μm. (Bottom) Quantification of BrdU-positive cells in the epidermis surrounding blisters (n= 3 (control) and 4 (Col17a1-/-) biological replicates). The data are shown as the mean ± SE. Student's t-test. NS, no significance.",
    "ncbi_link": "Col17a1: 12821"
  },
  {
    "caption": "Lineage tracing of K14CreER:R26R-mCherry:Col17a1-/- at P4. Scale bar: 100 μm.",
    "ncbi_link": "mCherry: 
Col17a1: 12821
Cre: 2777477
ER: 13982
K14: 16664"
  },
  {
    "caption": "K10/K14 (low magnification, left) and K14 (high magnification, middle and right) labeling of Col7a1-/- mouse (bottom) and littermate control (top) blistered skin at P2. Scale bar: 30 μm. Quantification of BrdU-positive cells per μm HF length (n=55 HFs from three control and 143 HFs from four Col7a1-/- mice). The data are shown as violin plots. Student's t-test. NS, no significance. Length of the major axis of keratinocytes in the regenerated epidermis (n=244 (control, L), and 132 (Col7a1-/-, L) cells from four mice, respectively) and in the surrounding intact epidermis (basal cells; n=200 (control, NL), 299 (Col7a1-/-, NL), from four mice, respectively). NL: nonlesional area. L: lesional area. The data are shown as violin plots. ****p<0.0001, one-way ANOVA test, followed by Tukey's test. NS, no significance.",
    "ncbi_link": "Col7a1: 12836"
  },
  {
    "caption": "D qRT-PCR  for  mRNA expression of the transcription factors Lef1  and Runx1 in epidermis of ABT-199 treated and control (Ctr) mice at P77 (n=3 biological replicates; mean ± standard error of mean (SEM); ** p<0.01, ns=not significant, two-tailed unpaired Student's t-test).",
    "ncbi_link": "Lef1: 16842
Runx1: 12394"
  },
  {
    "caption": "C qRT-PCR for mRNA expression of the  anoikis-related markers  Bim and  Bmf  in sorted n-B (non-bulge), bBSC (basal BSCs) and sbBSC (suprabasal BSCs) (n=3 biological replicates; mean ± standard error of mean (SEM); * p<0.05, ns=not significant, two-way ANOVA test).",
    "ncbi_link": "Bim: 12125
Bmf: 171543"
  },
  {
    "caption": "C FACS plot and quantification of keratinocytes stained  for  CD34  and Itgα6  in 8 week old control (Ctr) and Bcl-2EOE mice (n=3 biological replicates; mean ± standard deviation (SD); ns=not significant, two-tailed unpaired Student's t-test). suprabasal  (sbBSC, CD34+/Itgα6low), basal  (bBSC, CD34+/Itgα6high) BSCs.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "D  Immunofluorescence staining of  telogen backskin HF for BrdU  incorporation (1 h pulse, green) and DAPI (blue) in 8 week old control (Ctr) and Bcl-2EOE mice. Scale bar, 50 µm.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "A  Histology of P19 catagen backskin HF of control (Ctr) and Bcl-2EOE mice. RS: retracting strand, Scale bar, 50 µm. B Analysis of length and width of retracting strands of control (Ctr) and  Bcl-2EOE mice (n=4; multiple measurements/biological replicate; whiskers: min and max; boxes: median ± first and third quartile; **** p<0.0001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "C Itgα6  and aCas3 Immunofluorescence staining of  catagen tailskin HF of control (Ctr) and Bcl-2EOE mice  (n=4 biological replicates). Dashed lines: retracting strands. Scale bar, 100 µm. D Quantification of aCas3+ cells in the RS of P19 Ctr and Bcl-2EOE mice (n=4 biological replicates; mean ± standard deviation (SD); **** p<0.0001, two-tailed unpaired Student's t-test). HF:  hair follicle. ",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "F,G qRT-PCR for mRNA expression of the quiescence-related markers  Bmp6 (F) and Fgf18 (G) in epidermis of control (Ctr) and Bcl-2EOE mice  (P27), (n=4 biological replicates; mean ± standard error of mean (SEM); * p<0.05, *** p<0.001, two-tailed unpaired Student's t-test).",
    "ncbi_link": "Bcl-2: 12043
Bmp6: 12161
Fgf18: 14172"
  },
  {
    "caption": "B Immunofluorescence staining of  epidermal tail  whole mounts of control (Ctr), K15ΔNLef1 and K15ΔNLef1;Bcl-2EOE mice,  stained for keratin 15 (Krt15, green), activated Caspase 3   (aCas3, red) and DAPI (blue). Note increased number of aCas+ cells in the bulge of K15ΔNLef1 mice (arrows). B: bulge,  HG: secondary hair germ, SG: sebaceous gland. Scale bar, 100µm.",
    "ncbi_link": "Bcl-2: 12043
Lef1: 16842"
  },
  {
    "caption": "D  Immunofluorescence staining of epidermal tail  whole mounts of control (Ctr), K15ΔNLef1 and K15ΔNLef1;Bcl-2EOE mice, stained for keratin 15 (Krt15, green), BrdU (1 h pulse, red) and DAPI (blue). Note increased  number  of BrdU+ cells in the bulge of K15ΔNLef1 mice (arrows). B: bulge, HG: secondary hair germ, SG: sebaceous gland. Scale bar, 100µm",
    "ncbi_link": "Bcl-2: 12043
Lef1: 16842"
  },
  {
    "caption": "B,C Tumour incidence (B) and frequency (C) in Ctr, Bcl-2EOE, K15ΔNLef1 and K15ΔNLef1;Bcl-2EOE mice (n=10 biological replicates; mean ± standard error of mean (SEM)).",
    "ncbi_link": "Bcl-2: 12043
Lef1: 16842"
  },
  {
    "caption": "D  Histology of sebaceous tumours of K15ΔNLef1  and K15ΔNLef1;Bcl-2EOE mice. Scale bar, 100µm.",
    "ncbi_link": "Bcl-2: 12043
Lef1: 16842"
  },
  {
    "caption": "(A) Atg5fl/fl Cre− and Atg5fl/fl Cre+ bone marrow‐derived macrophages (BMMs), pretreated overnight with 100 ng/ml LPS, were stimulated for 1 h with the inflammasome agonist nigericin (20 μM) with (Starvation; EBSS) or without (Full; full medium) autophagic induction. Cell culture supernatants were assayed for murine IL‐1β by ELISA. Data represent mean values±s.d. (n≥3); *P0.05.",
    "ncbi_link": "Cre: 
Atg5: 11793"
  },
  {
    "caption": "(B) LPS‐pretreated Atg5fl/fl Cre− and Atg5fl/fl Cre+ BMMs were stimulated with 20 μM nigericin for 1 h in OptiMEM and the release of active caspase‐1 and IL‐1β was determined by immunoblotting.",
    "ncbi_link": "Cre: 
Atg5: 11793"
  },
  {
    "caption": "(F) BMMs were transfected with scramble (Scr) control siRNA or siRNAs against ASC and NLRP3. After 48 h following transfection, cells were treated overnight with LPS and subjected to nigericin (20 μM) and starvation for 1 h. Data represent mean values±s.d. (n⩾3); *P0.05.",
    "ncbi_link": "NLRP3: 216799
ASC: 66824"
  },
  {
    "caption": "(G) Immunoblot analysis of ASC and NLRP3 knockdowns.",
    "ncbi_link": "NLRP3: 216799
ASC: 66824"
  },
  {
    "caption": "(H) BMMs were transfected with scramble (Scr) control siRNA or siRNAs against ASC and NLRP3. After 48 h following transfection, cells were treated overnight with LPS and subjected to silica (250 μg/ml) and starvation for 1 h. Data represent mean values±s.d. (n⩾3); *P0.05.",
    "ncbi_link": "NLRP3: 216799
ASC: 66824"
  },
  {
    "caption": "(I) Colocalization of IL‐1β with the basal autophagic machinery factor LC3. Fluorescence: LC3 (green, Alexa488); IL‐1β (red, Alexa568). BMMs were from GFP-LC3 knock‐in mice, treated with LPS then prepared for immunofluorescence microscopy using fluorescently labelled antibodies against GFP and IL‐1β.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(D) Colocalization of cathepsin B with the basal autophagic machinery factor LC3 and IL‐1β. Fluorescence; LC3 (green, Alexa488), IL‐1β (red, Alexa568), and cathepsin B (blue, Alexa633). BMMs from GFP-LC3 knock‐in mice were treated with LPS and then analysed for immunofluorescence.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(G) LPS‐pretreated Atg5fl/fl Cre− and Atg5fl/fl Cre+ BMMs were stimulated with 20 μM nigericin for 1 h in OptiMEM and release of cathepsin B was determined by immunoblotting. Figure source data can be found in Supplementary data.",
    "ncbi_link": "Cre: 
Atg5: 11793"
  },
  {
    "caption": "(A) Colocalization of Rab8a with the basal autophagic machinery factor LC3 and IL‐1β. Fluorescence; LC3 (green, Alexa488), IL‐1β (red, Alexa568), Rab8a (blue, Alexa633). BMMs from GFP-LC3 knock‐in mice were pretreated with LPS and analysed by immunofluorescence microscopy. Arrows indicate triple colocalization.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(D) BMMs were transfected with siRNAs against Rab8a or scramble (Scr) control. At 24 h after the first transfection, cells were transfected again with siRNA, treated with LPS and the day after subjected to nigericin in full medium for 1 h, and IL‐1β secretion measured.",
    "ncbi_link": "Rab8a: 17274"
  },
  {
    "caption": "(F) RAW 264.7 macrophages were transfected with GFP‐tagged Rab8a constructs (WT, wild type; S22N, dominant‐negative mutant), treated overnight with LPS and stimulated for 1 h with 20 μM nigericin along with induction of autophagy by starvation. IL‐1β secretion was measured by ELISA. Data represent mean values±s.d. (n≥3); *P0.05. Figure source data can be found in Supplementary data.",
    "ncbi_link": "Rab8a: 17274"
  },
  {
    "caption": "(A) BMM cells were transfected with scramble (Scr) control siRNA or siRNA against GRASP55. After 48 h of transfection, cells were treated with LPS and the day after subjected to 20 μM nigericin in EBSS, and secreted IL‐1β was measured by ELISA. Data represent mean values±s.d. (n⩾3); *P0.05. Inset: Immunoblot analysis of GRASP55 knockdown.",
    "ncbi_link": "GRASP55: 71680"
  },
  {
    "caption": "(A, B) Effect of GRASP55 on autophagy induction by measuring LC3‐II. BMM cells were transfected with GRASP55 siRNAs or scramble (Scr) control. At 72 h post transfection, cells were induced for autophagy, treated or not with Bafilomycin A1 (Baf) to inhibit autophagic degradation and LC3‐II/actin ratios determined by immunoblotting (A) followed by densitometry (B). Data represent mean values±s.d. (n⩾3); *P0.05.",
    "ncbi_link": "GRASP55: 71680"
  },
  {
    "caption": "(C, D) RAW 264.7 was transfected with GRASP55 siRNAs or scramble (Scr) siRNA control. Following 48 h of siRNA treatment, cells were transfected with RFP-GFP-LC3 plasmid (GFP is sensitive to acidification, whereas RFP is not), after 24 h induced for autophagy in EBSS for 1 h and autophagic induction and flux quantified (graph in D) by determining the number of early autophagic organelles (GFP+RFP+ puncta) and autolysosomal organelles (GFP−RFP+ puncta) per cell as illustrated in fluorescent images (yellow arrows, GFP+RFP+; red arrows, GFP−RFP+). Total, yellow+red puncta per cell. Data represent mean values±s.d. (n⩾3); *P0.05. Figure source data can be found in Supplementary data.",
    "ncbi_link": "GRASP55: 71680"
  },
  {
    "caption": "(A) Atg5fl/fl Cre− and Atg5fl/fl Cre+ bone marrow‐derived macrophages (BMMs), pretreated overnight with 100 ng/ml LPS, were stimulated for 1 h with the inflammasome agonist nigericin (20 μM) with (Starvation; EBSS) or without (Full; full medium) autophagic induction. Cell culture supernatants were assayed for murine IL‐1β by ELISA. Data represent mean values±s.d. (n⩾3); *P0.05.",
    "ncbi_link": "Cre: 
Atg5: 11793"
  },
  {
    "caption": "(B) LPS‐pretreated Atg5fl/fl Cre− and Atg5fl/fl Cre+ BMMs were stimulated with 20 μM nigericin for 1 h in OptiMEM and the release of HMGB1 was determined by immunoblotting. Figure source data can be found in Supplementary data.",
    "ncbi_link": "Cre: 
Atg5: 11793"
  },
  {
    "caption": "(a) Lipid phosphatase activity of Paladin, wild-type and phosphatase-dead C/S mutant, towards PI(4,5)P2 and PI(3,4,5)P3 substrates. Positive control; wild-type phosphatase and tensin homolog (PTEN); negative control; lipid phosphatase-dead C124S PTEN. Mean±SEM, Paired t-test, n=3 biological replicates. Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "Paladin: 27143
PTEN: 5728"
  },
  {
    "caption": "(a) Cell surface VEGFR2 levels detected by cell surface biotinylation, using thiol-cleavable sulfo-NHS-SS-biotin, of HDMEC transfected with PALD1 siRNA (#1 and #2) or non-targeting control ("c") siRNA, followed by VEGF-A stimulation (50 ng/ml) for indicated time periods. Total lysates (input) and streptavidin (SA) pull down, immunoblotted for VEGFR2, Paladin, and actin. 'No biotin ctrl', cells not treated with sulfo-NHS-SS-biotin. (b) Quantification of data in (a). VEGFR2 surface levels (data pooled for the indicated time points) normalized to total VEGFR2 levels and compared between control and siRNA treated HDMEC. n=4 for each time point, biological replicates, Mean±SEM. Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "(c) Internalized pool of VEGFR2 after VEGF-A treatment (50 ng/ml) of non-transfected HDMEC ("NT") or HDMEC transfected with PALD1 siRNA (#1 and #2) or non-targeting control siRNA ("c"). Cell surface biotinylation was performed prior to VEGF-A stimulation and at indicated time points, remaining cell surface biotin was stripped and the internalized pool of VEGFR2 was collected by SA pull down. Immunoblotting of the total lysate (input) and SA pull down fraction for VEGFR2, Paladin and actin. (d) Quantification of data in (c). Data were normalized to total VEGFR2 levels in the lysate after subtraction of signals in biotinylated and stripped samples. Mean±SEM, unpaired t-test for indicated time points, normalized to cntrl siRNA sample. n=3 for each time point, biological replicates. Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "(e) Analysis of EEA1 and VEGFR2 vesicles following PALD1 knockdown. Representative images of VEGFR2 (green)/EEA1 (red) double-positive (yellow) vesicles in negative control siRNA, and PALD1 KD#2 siRNA-silenced HDMEC at 0, 2 and 10 min of VEGF-A stimulation (50 ng/ml). DAPI in blue, scale bar: 10 µm. Inset shows only EEA1 channel, scale bar: 10 µm. (f) Quantification of (e), number of EEA1 positive (top) or VEGFR2-EEA1 double-positive vesicles (bottom) per field of view. Mean±SEM, Two-way ANOVA, n=3 biological replicates. Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "(g) HDMEC stained for PI(4,5)P2 (cyan), VE-cadherin (red) and Paladin (yellow in inset) following treatment using negative control or PALD1 (KD#2) siRNA. VEGF-A stimulation for 0, 2 or 10 minutes (50 ng/ml). DAPI in blue. Scale bar: 10 µm (h) Quantification of (g), Total PI(4,5)P2 signal (top) or intracellular PI(4,5)P2 not overlapping with VE-cadherin (bottom). Mean±SEM, two-way ANOVA, n=3 biological replicates. Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "Signalling downstream of VEGF-A/VEGFR2 assessed in HDMEC, untreated (NT, non-transfected), transfected with non-targeting siRNA (c/cntrl), or with two different PALD1-targeting siRNAs (KD#1 and KD#2), and treated with VEGF-A for 0-10 and 0-20 min, respectively. Immunoblotting of cell lysates for phosphorylated (p) VEGFR2 (pY1175), total VEGFR2 Actin served as loading control (a PALD1 knockdown was verified by blotting for Paladin. Quantification of pVEGFR2 (normalized to total VEGFR2) (b) Mean±SEM, two-way ANOVA, n=3 biological replicates. Data information: *p < 0.05, **p < 0.01.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "Signalling downstream of VEGF-A/VEGFR2 assessed in HDMEC, untreated (NT, non-transfected), transfected with non-targeting siRNA (c/cntrl), or with two different PALD1-targeting siRNAs (KD#1 and KD#2), and treated with VEGF-A for 0-10 and 0-20 min, respectively. Immunoblotting of cell lysates for phosphorylated Erk1/2 (pT202 and pY204), and total Erk. Actin served as loading control c). PALD1 knockdown was verified by blotting for Paladin. Quantification of pErk1/2 (normalized to total Erk1/2) (d). Mean±SEM, two-way ANOVA, n=3 biological replicates. Data information: *p < 0.05, **p < 0.01.",
    "ncbi_link": "PALD1: 27143"
  },
  {
    "caption": "(e-f) Immunoblotting on total heart lysates from adult Pald1+/+ and Pald1-/- mice, tail-vein injected with VEGF-A (0.25µg/g body weight) or PBS for the indicated time points, for Paladin, phosphorylated and total levels of VEGFR2, Erk1/2 and β2-microglobulin (β 2-MG, loading control). (f) Quantification of pVEGFR pY1173 normalized to total VEGFR2 (n=3), total VEGFR2 levels normalized to total loading control (n=4), pT202/pY204 Erk1/2 normalized to Erk1/2 (n=5). Mean±SEM, multiple t-test with Holm-Sidak correction (total VEGFR2), two-way ANOVA (others). Data information: *p < 0.05, **p < 0.01.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(a, b) Delayed vascular outgrowth and hyperdense vascular front in isolectinB4-stained P5 retina from Pald1-/- mouse compared with Pald1+/+ (a). Orange arrow indicates radial expansion of the vascular plexus in the Pald1+/+ retina. Scale bar: 1 mm. Quantification of radial expansion (b) as shown in (a) normalized to wild type litter mates. Mean±SEM, unpaired t-test. n=14 litters, 18 wild type and 23 knock-out pups. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(c, d) Increased filopodia number in Pald1-/- mouse retina at vascular front, visualized by isolectinB4 staining (c). Scale bar: 50 μm. Quantification of filopodia per 100 µm at the vascular front (d). Mean±SEM, unpaired t-test. n=3 litters, 7 wild type and 5 knock-out pups. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(g, h) pT202/pY204 Erk1/2 immunostaining (black) in Pald1+/+ and Pald1-/- P5 pups. IsolectinB4 (white) visualizes the entire vasculature. Scale bar: 100 μm. Quantification of pT202/pY204 Erk1/2 area (h) as in the black stippled square in (g) (400 µm from the retina rim), normalized to isolectinB4 area. Mean±SEM, unpaired t-test. n=5 litters, 14 wild type and 10 knock-out retinas per genotype. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(i) Quantitative real-time PCR analysis of P4-P5 retinas from Pald1+/+ and Pald1-/- pups. Ccnd1 transcript levels, normalized to Gapdh. Mean±SEM, unpaired t-test. n=10 Pald1+/+ and 14 Pald1-/- pups. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Ccnd1: 12443
Gapdh: 14433
Pald1: 27355
Pald1: 27143"
  },
  {
    "caption": "(j) Cyclin D1 (black) and isolectinB4 (white) staining of P5 retinas from Pald1+/+ and Pald1-/-pups. Scale bar: 100 µm.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(k) Quantification of number of Cyclin D1 positive nuclei normalized for isolectinB4 area in retinas from Pald1+/+ and Pald1-/ P5 pups. Mean±SEM, unpaired t-test. n=7 Pald1+/+ and 6 Pald1-/- pups. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(l) Quantification of relative radial expansion in vehicle (n=2 litters, 5 Pald1+/+ and 4 Pald1-/- pups) and MEK inhibitor (U0126)-treated pups (n=4 litters, 7 Pald1+/+ and 5 Pald1-/- pups). MEK inhibitor/vehicle was administered twice at 12h interval at P4 and eyes collected at P5. Each dot is one mouse. Mean±SEM, one-way ANOVA, n=4-7. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(m) Quantification of the tip cell number in vehicle- (n=3 litters, 5 Pald1+/+ and 5 Pald1-/- pups) and MEK inhibitor (U0126)-treated pups (n=3 litters, 5 Pald1+/+ and 4 Pald1-/- pups). MEK inhibitor/vehicle administered twice at P5 at 2-h intervals, and eyes collected 2 h after the second injection. Each dot is one mouse. Mean±SEM, one-way ANOVA. Data information: *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "(a) Eyes from Pald1+/LacZ mice collected at P17 from untreated animals or animals with oxygen-induced retinopathy (OIR). Pald1-promoter driven LacZ expression and X-gal staining generated signals in capillaries, veins and arteries in the OIR retina at P17 compared to the normoxia control with predominantly arterial LacZ expression. Scale bar: 1 mm.",
    "ncbi_link": "LacZ: 
Pald1: 27355"
  },
  {
    "caption": "(c) Eyes from adult Pald1LacZ/+ mice collected at 72 h after single-bolus intravitreal injection of 1 μg VEGF-A, and PBS in the contralateral eye, followed by X-gal staining. Arrow indicates Pald1 promoter activity in veins (outlined by dashed line) specifically after VEGF-A treatment. A, artery; V, vein. Scale bar: 100 μm.",
    "ncbi_link": "LacZ: 
Pald1: 27355"
  },
  {
    "caption": "(d-f) Representative images of isolectinB4-stained P17 retinas from OIR-challenged Pald1+/+ and Pald1-/- mice (detailed view in the insets) (d). Scale bar: 1 mm (inset 250 µm). Quantification of neovascular tuft area (e) and avascular area (f). Each dot represents the mean of both retinas per mouse. Mean±SEM, unpaired t-test, n=3 litters, 4 Pald1+/+ and 3 Pald1-/- pups. Data information: *p < 0.05, **p < 0.01.",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "g) Representative images of retina vasculature immunostained for isolectinB4 and pT202/pY204 Erk1/2 (pErk1/2). pErk1/2 staining within the vessels is also visualized using a 16-color heatmap to display staining intensity. Scale bar: 30 µm (inset 10µm). (h) Quantification of pErk1/2 immunostaining as shown in (g) within isolectinB4-positive vessels, as fold-change of pErk1/2 stained area. Each dot represents the mean of both retinas per mouse. Mean±SEM, unpaired t-test, n=3 litters, 5 Pald1+/+ and 5 Pald1-/- pups. Data information: *p < 0.05, **p < 0.01. ",
    "ncbi_link": "Pald1: 27355"
  },
  {
    "caption": "B HEK-293T cells were transfected with Pim1 and each EDC3 domain (Fig. 2A) fused to the C-terminus of the GFP-tagged vector. The individual fragments were immunoprecipitated with GFP-Trap beads and analyzed by Western blotting with the indicated Abs. EDC3 wild type (W), F1, F2, F3, F4 were EDC3 fragments vector fused to GFP. The C1 lane was only transfected with the GFP Flag vector while C2 contained EDC3 wild type fused to GFP and no Pim1 but empty vector control (pcDNA3).",
    "ncbi_link": "EDC3: 80153
Pim1: 5292"
  },
  {
    "caption": "F PC3-LN4 CRISPR-Ctr and Pim1 KO cells were treated with PIMi (PIM447, 3μM), AKTi (GSK690693, 5μM), or the combination for 24 h. Extracts were subjected to Western blotting with the indicated Abs.",
    "ncbi_link": "CRISPR: 
Pim1: 5292"
  },
  {
    "caption": "A, B Western blot of whole-cell (WCL) and P-body (PB) purified from PC3-LN4 cells stably expressing GFP-DCP1a used as a P-body tag. The P-bodies (PB) were isolated with GFP-Trap beads and analyzed by Western blotting with the indicated Abs.",
    "ncbi_link": "GFP: 
DCP1a: 55802"
  },
  {
    "caption": "A PC3-LN4 Naïve and CRISPR/Cas9 genome-edited EDC3 S161A (SA), S161D (Fredriksson et al.), and EDC3 knock-out (KO) cell lines were plated (4000 cells/well in 24 well plates) and imaged every 12 h using phase contrast in the IncuCyte ZOOM platform. The graph shown was generated with IncuCyte Basic Software following 5 days of growth. The experiments were done in triplicates. Values are mean +/- S.E.M. p values<0.05, calculated using unpaired student t-test. Data information: All invasion and migration assays were performed in triplicates and 6 different fields at 10x magnification were counted in 3 separate inserts. The data are presented as the mean +/- S.D. p values<0.05, calculated using unpaired student's t-test.",
    "ncbi_link": "Cas9: 
CRISPR: 
EDC3: 80153"
  },
  {
    "caption": "H Relative mRNA expression of ITGA6, ITGB1, and KLF4 in PC3-LN4 EDC3 KO-C60 cells, containing reexpressed EDC3 WT or EDC3 S161A mutant cDNAs Data information: Real-time PCR data",
    "ncbi_link": "EDC3: 80153
ITGA6: 3655
ITGB1: 3688
KLF4: 9314"
  },
  {
    "caption": "A Two independently derived CRISPR/Cas9 PC3-LN4 EDC3 S161A mutants (EDC3 SA#1, #2) and wild type cells were injected subcutaneously in the flank (5X106) of SCID mice (n=8/group), and tumor growth was monitored until the control group reached 1000 mm3. The subcutaneous tumor volume measurement (mm3) was done as outlined in Materials and Methods. Data are presented as mean ± SEM, (n = 8/group).",
    "ncbi_link": "Cas9: 
CRISPR: 
EDC3: 80153"
  },
  {
    "caption": "Heatmaps of enriched hippocampus phosphotyrosine peptides in hippocampus tissue from CK-p25 animal mice. Colors indicate fold change relative to control animals on a log2-scale. Row colors (left) indicate peptides from predicted cell-type specific proteins. Green = Astrocyte, Orange = Neuron, Blue = Microglia, Purple = Oligodendrocyte.",
    "ncbi_link": "p25: 12569"
  },
  {
    "caption": " Colors indicate fold change relative to control animals on a log2-scale. Row colors (left) indicate peptides from predicted cell-type specific proteins. Green = Astrocyte, Orange = Neuron, Blue = Microglia, Purple = Oligodendrocyte. (E) Heatmap showing enriched hippocampus phosphotyrosine peptides from 6 month old Tau P301S animals. ",
    "ncbi_link": "Tau: 17762"
  },
  {
    "caption": "(A) Immunofluorescence (IF) staining showing Siglec-F and Iba1 localization in hippocampus CA3 region of 3wk induced CK (top) or CK-p25 (bottom) mice. Scale bars = 50 μm. Colors are: Magenta = Iba1, Cyan = Siglec-F. Images are 60x super-resolution max z-stack projections taken from coronal slices. (B-C) Percent area coverage of (B) Iba1 and (C) Iba1-proximal Siglec-F between CK and CK-p25 mice across hippocampal regions. Bars indicate mean ± 95% CI; n = 3-4 animals; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided. ",
    "ncbi_link": "p25: 12569"
  },
  {
    "caption": " (A) Confluency doubling times quantified from BV-2 cells with stable retroviral expression of Siglec-F and related human Siglec constructs. Plots indicating doubling time (normalized to 2xY->F constructs) estimated from Incucyte bright-field images. Cells grown in media alone or + 50 mU sialidase (+SA). Bars indicate mean ± 95% CI; n = 3-12 replicates; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided. Dotted line indicates mean of 2xY->F groups. ",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "(B) Flow cytometry quantification of cell live / dead markers Annexin-V and propidium iodide on BV-2 cells with stable retrovirus expression of Siglec-F constructs. % parent values are shown for early apoptotic (Annexin-V+;PI‑), late apoptotic (Annexin-V+;PI‑), and necrotic (Annexin-V-;PI+) populations. Bars indicate mean ± SD; n = 8 replicates.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": " (C) Confluency doubling times quantified from BV-2 cells with dox-inducible expression of Siglec-F constructs. Plots indicating doubling time (normalized to 2xY->F constructs) estimated from Incucyte bright-field images. Bars indicate mean ± SD; n = 8 replicates; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided. Dotted line indicates mean of 2xY->F group. ",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "(F) Expression levels of C1qa, IL-1β, and β-actin by qPCR analysis in BV-2 cells with inducible Siglec-F expression after 48 hours of treatment with 500 ng/mL doxycycline. Fold Change values are equal to 2ΔΔCq normalized relative to GADPH mRNA levels. Bars indicate mean ± 95% CI; n = 6 replicates; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided. Dotted line indicates mean of 2xY->F group.",
    "ncbi_link": "β-actin: 11461
C1qa: 12259
GADPH: 14433
IL-1β: 16176
Siglec-F: 233186"
  },
  {
    "caption": "(G) Western blot showing pro-IL-1β and β-tubulin in BV-2 cells induced to express Siglec-F at 0 and 48 hours.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "(B-C) Volcano plots showing phosphotyrosine peptides that were (B) increased or (C) decreased after Siglec-F expression. Plots show Siglec-F compared to 2xY->F mutant data integrated across all three runs. Protein names are shown for altered peptides. Labels are only shown for peptides with maximum directional change from each protein. Labels colored according to GO terms: magenta = signal transduction, red = endosome, cyan = cell adhesion, yellow = cytoskeleton, green = metabolism.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": " (D) Heatmap showing phosphosites in CK-p25 which overlapped in their directional change with BV-2 Siglec-F-associated sites. Colors indicate fold change relative to 2xY->F controls. ",
    "ncbi_link": "p25: 12569
Siglec-F: 233186"
  },
  {
    "caption": " Heatmap showing phosphosites from CD33, Siglec-5, and Siglec-8 overexpression that were increased with Siglec expression and shared their directional change with Siglec-F. Siglec-F column indicates average of all untreated Siglec-F replicates. Color scale is same as (D). ",
    "ncbi_link": "CD33: 945
Siglec-5: 8778
Siglec-8: 27181
Siglec-F: 233186"
  },
  {
    "caption": " Heatmap showing phosphosites from CD33, Siglec-5, and Siglec-8 overexpression that were decreased with Siglec expression and shared their directional change with Siglec-F. Siglec-F column indicates average of all untreated Siglec-F replicates. Color scale is same as (D). ",
    "ncbi_link": "CD33: 945
Siglec-5: 8778
Siglec-8: 27181
Siglec-F: 233186"
  },
  {
    "caption": "(G) Western blot quantification of myc, SHP-2, and SHP-1 from myc co-IP eluates. Co-IP lysates were prepared from BV-2 cells stably expressing Siglec-F and optionally treated with 1 μM SHP099.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "(B-C) Flow cytometry quantification of fluorescent monomeric Aβ uptake and Siglec-F expression for (B) Siglec-F and (C) Siglec-F 2xY->F. Siglec-expressing cells were plated with empty vector control cells in the same well alongside fluorescent substrates.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "(G) pHrodo Dextran uptake in BV-2 cells with stable expression of Siglec-F estimated by Incucyte measurements. Bars indicate mean ± 95% CI; n = 6 replicates; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided.",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": " (H) pHrodo dextran uptake in BV-2 cells stably expressing Siglec-F with 0 - 2.5 μM SHP099 treatment. Data is from the same experiment as (G). ",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": " (I) Confluency doubling times for BV-2 cells with stable expression of Siglec-F with 0 - 2.5 μM SHP099 treatment. Data is from the same experiment as (G). Bars indicate mean ± 95% CI; n = 4 replicates; *: p < 5e-2, **: p < 1e-2, ***: p < 1e-3, ****: p < 1e-4; ns: not significant, using unpaired Student's t-test, two-sided. Dotted line indicates mean of untreated 2xY->F group. ",
    "ncbi_link": "Siglec-F: 233186"
  },
  {
    "caption": "A. The expression of EP subtypes in bone marrow myeloid cells and colon tumor myeloid cells. The short black lines indicate individual expressions, the blue and yellow lines indicate the average expression level in each condition. The grey dotted lines represent the overall average between Ptger1 and Ptger3 or Ptger2 and Ptger4.",
    "ncbi_link": "Ptger1: 19216
Ptger2: 19217
Ptger3: 19218
Ptger4: 19219"
  },
  {
    "caption": "Relative expression of selected M1, M2 markers on flow-sorted M1 macrophages (D), M2 macrophages (E) from CT26 tumors. Data are normalized to β-actin expression levels (n = 5).",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "M-CSF induced mouse bone marrow derived macrophages (BMMs) were stimulated with 50 ng/mL mouse recombinant IFN-γ (A) in the absence or presence of PGE2 ± varying concentrations of TP-16 for 12 hr. The mRNA levels of selected M1 markers (Cxcl10 and Tnfa) were measured by q-PCR. Data are normalized to β-actin expression levels (n=3).",
    "ncbi_link": "β-actin: 
Cxcl10: 15945
Tnfa: 21926"
  },
  {
    "caption": "B. M-CSF induced mouse bone marrow derived macrophages (BMMs) were stimulated with 20 ng/mL mouse recombinant IL-4 (B) in the absence or presence of PGE2 ± varying concentrations of TP-16 for 12 hr. The mRNA levels of selected M2 markers (Arg-1 and Ym-1) were measured by q-PCR. Data are normalized to β-actin expression levels (n=3).",
    "ncbi_link": "β-actin: 
Arg-1: 11846
Ym-1: 12655"
  },
  {
    "caption": "D. Bone marrow cells were treated with GM-CSF/IL-6 for 6 days to induce MDSCs and thereafter, with PGE2 ± varying concentrations of TP-16 for 12 hr. The mRNA levels of selected MDSC markers (Arg-1, Ptgs2, Il-4, and Il-10) were measured by qPCR. Data are normalized to β-actin expression levels (n=3).",
    "ncbi_link": "β-actin: 
Arg-1: 11846
Il-10: 16153
Ptgs2: 19225"
  },
  {
    "caption": "D Percentage of GFP+ cells within T cell subpopulations 17 days after CD40LG editing of healthy male donor (HD; n=11) or patient (Pt; n=1) derived CD4+ T cells, measured by FACS analysis. Median ± IQR.",
    "ncbi_link": "CD40LG: 959"
  },
  {
    "caption": "G Percentage of TCRBV families detected by spectratyping. UT, sorted edited (GFP+), sorted non-edited (GFP-) CD4+ T cells derived from male HD (n=1) or patient (Pt; n=1) were analyzed at 17 days after CD40LG editing.",
    "ncbi_link": "CD40LG: 959"
  },
  {
    "caption": "B Percentage of NGFR+ cells or HDR at 17 days after CD40LG editing of male HD bulk edited, sorted NGFR+ or sorted NGFR- CD4+ T cells (n=7 for each group). Median ± IQR.",
    "ncbi_link": "CD40LG: 959"
  },
  {
    "caption": "I Dot plot depicting the ratio between expression of CD40LG edited mRNA (codon-usage optimized, CO) and CD40LG wild-type mRNA (WT) in cells edited with three different donor templates from Fig EV2H. Three independent experiments (n=3 EF1a.GFP, 1 IRES.NGFR, 3 IRES.GFP). Median ± IQR.",
    "ncbi_link": "GFP: 
CD40LG: 959
EF1a: 1915
NGFR: 4804"
  },
  {
    "caption": "J Time course of expression of WT-CD40LG mRNA or CO-CD40LG mRNA, measured as fold change (FC) on IPO8 housekeeping gene and normalized to T0. Sorted edited (+) and sorted unedited (-) CD4+ T cells were analyzed before and 3, 6, 12 hr after Actinomycin D treatment (n=1 for each group).",
    "ncbi_link": "IPO8: 
CD40LG: 959"
  },
  {
    "caption": "D Bar plot showing percentage of EGFR+ T cells at 3 days after treatment with 5 nM or 1 nM of immunotoxin, antibody or toxin, measured by FACS Analysis. Friedman test with Dunn's multiple comparisons. P-values were adjusted with Bonferroni's correction to account for multiple comparisons (**p=0.0052 and **p=0.0024 for immunotoxin vs antibody and **p=0.0010 and **p=0.0024 for immunotoxin vs toxin, referring to EGFRmod1 and EGFRmod2 respectively). Different dose-conditions were used as a unified group for statistical analysis (n=10 for each group). Median ± IQR.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "B Percentage of HDR in HSPC subpopulations at 4 days after CD40LG editing, measured by molecular analysis (ddPCR). Cells were edited with donor template either comprising only the corrective cDNA (NR; n=4), or carrying the selector cassette IRES.NGFR (NGFR; n=5) and sorted according to surface markers: CD34-; CD34+CD133-CD90-; CD34+CD133+CD90-; CD34+CD133+CD90+. CD34+CD133+CD90+/CD90- and CD34+CD133-/CD34- conditions were used as unified groups for statistical analysis. The comparisons between the groups were performed with LME models accounting for the different subpopulations included in the analysis and with random effects defined to account for the same donor. In comparison about CD34+CD133+CD90+/CD90-, the percentages were used in square root scale to meet the assumption of normality of the residuals of the model. For CD34+CD133+CD90+/CD90-, **p= 0.0035, for CD34+CD133-/CD34- p=0.2051. Median ± IQR.",
    "ncbi_link": "CD40LG: 959
NGFR: 4804"
  },
  {
    "caption": "C Population composition in UT or bulk edited HSPC from (B) (n=8 for each group, except UT cells from NGFR group, n=7). Paired Wilcoxon's test, to account for the same donor, with p-values adjusted with Bonferroni's correction to account for multiple testing. Analysis was performed separately for NR and NGFR groups. Mean ± SEM.",
    "ncbi_link": "NGFR: 4804"
  },
  {
    "caption": "F TNP-KLH specific IgG in sera of transplanted mice collected at the times indicated in (A) (n=7 CPA 300, 13 NC for first boost and 4 CPA 300, 9 NC for second boost). Sera from vaccinated WT (n=5) and CD40lg-/- (n=5) mice were used as positive and negative controls, respectively. Two independent experiments. Comparisons of first boost data were performed with an LME model, accounting for multiple experiments, followed by appropriate post-hoc analysis (see Appendix Supplementary Statistical Methods). The reported statistical comparisons refer only to the overall difference among groups (****p<0.0001 in all comparisons). Median ± IQR.",
    "ncbi_link": "CD40lg: 21947"
  },
  {
    "caption": "G Average area of PNA+ foci in splenic sections of experimental mice from (B), calculated as ratio between total PNA+ area and number of PNA+ foci/cells. Kruskal-Wallis test followed by post-hoc analysis with Dunn's test (n=9 CD40LG, 6 WT, 18 NC, 8 CPA300). P-values were adjusted with Bonferroni's correction to account for multiple comparisons (*p=0.0149, **p=0.0065 and ****p<0.0001). Mean ± SEM.",
    "ncbi_link": "CD40LG: 21947"
  },
  {
    "caption": "H Detection of splenic TNP-KLH specific IgM (left) and IgG (right) -secreting cells by ELISPOT assay (n=7 NC, 4 CPA300, 3 WT, 2 CD40LG). Spots were counted by an ELISPOT Reader using a size range of 0.005-1 mm. Median ± IQR.",
    "ncbi_link": "CD40LG: 21947"
  },
  {
    "caption": "E TNP-KLH specific IgG concentration in sera of mice from (B) collected before (day 35; pre) and after (day 49; post) the first boost (n=13 NC, 19 CPA 300, 4 CPA 200, 5 ALS, 6 ANTI-CD4; three independent experiments) and at day 81 (pre) and 89 (post) for the second boost (n=4 NC, 4 CPA 300, 4 CPA 200, 5 ALS, 6 ANTI-CD4). Sera from vaccinated WT (n=5) and Cd40lg-/- (n=5) mice were used as positive and negative controls, respectively. For early challenge data, comparisons were performed with an LME model, accounting for multiple experiments, followed by appropriate post-hoc analysis (see Appendix Supplementary Statistical Methods). The reported statistical comparisons refer only to the overall difference among groups (***p=0.0002 and ****p<0.0001 in all comparisons). CPA200 was not included in the analysis because n=4. WT group, not indicated in the figure, is significantly different from all groups (p<0.0001 in all comparisons). Of note, regarding the comparisons between time-points, the groups CPA 300 and WT show a significant increase between pre and post values (p<0.0001 for both), while all other groups show a significant decrease between pre and post values (p<0.0001 for all except p=0.0022 for ANTI-CD4). Median ± IQR.",
    "ncbi_link": "Cd40lg: 21947"
  },
  {
    "caption": "H TNP-KLH specific IgG concentration in sera of mice from (F) collected before (day 36, pre) and after (day 50, post) the first boost (n=6 NC, 11 CPA 300, 11 CPA 200) and at day 212 (pre) and 219 (post) for the second boost (n=6 NC, 11 CPA 300, 9 CPA 200). Sera from vaccinated WT (n=11) and Cd40lg-/- (n=5) mice were used as positive and negative controls, respectively. Comparisons were performed with an LME model followed by an appropriate post-hoc analysis, separately for each challenge data (Appendix Supplementary Statistical Methods). Reported statistical comparisons refer to the overall difference among groups, for early challenge data (*p=0.0282 and **p=0.0037), while to differences between time-points within each group, for late challenge data (**p=0.0018 and ****p<0.0001 in both comparisons). Of note, in the late challenge data, no significant overall differences were observed among the groups. Median ± IQR.",
    "ncbi_link": "Cd40lg: 959"
  },
  {
    "caption": "E Quantitation of P. murina rRNA in lung homogenate of mice from (A) transplanted with different ratios of WT HSPC cells (n=8 100% WT, 7 25% WT, 7 10% WT, 8 0% WT) and infected with the pathogen. Results are expressed in P.murina/HPRT RNA copies. Kruskal-Wallis test followed by post-hoc analysis with Dunn's test. P-values were adjusted with Bonferroni's correction to account for multiple comparisons. Only the groups 100% WT and 0% WT resulted to be significantly different (**p=0.0028). Median ± IQR.",
    "ncbi_link": "HPRT: "
  },
  {
    "caption": "H Quantitation of P. Murina rRNA in lung homogenate of mice adoptively transferred (n=9 CD40LG + T cells) or not (n=8 CD40LG) with in vivo primed CD4+ T cells in absence of conditioning and infected with the pathogen. Results are expressed in P.Murina/HPRT RNA copies. Mann-Whitney test. ***P-value of the comparison = 0.0003. Median ± IQR.",
    "ncbi_link": "HPRT: 
CD40LG: 21947"
  },
  {
    "caption": "(A) Netrin-1 (NTN1) gene expression profiling from 6 adults control brains using microarray data from the Allen Human Brain Atlas.",
    "ncbi_link": "Netrin-1: 9423
NTN1: 9423"
  },
  {
    "caption": "(B) Reporter gene expression in the midbrain (substantia nigra (SN) and ventral tegmental area (VTA)) of netrin-1+/lacZ+ adult (P60) mice incubated with S-Gal. (Scale bar, 2000 µm). Two coronal sections of the mice midbrain are shown from the more anterior is shown in the upper panel.",
    "ncbi_link": "lacZ: 945006
netrin-1: 18208"
  },
  {
    "caption": "(A) Representative images of dopamine neurons (TH-positive) in the substantia nigra (SN) (left panel) and in the SN and striatum (right panel top, and bottom respectively) by immunofluorescence, six weeks after the intranigral injection of control (CTL) (AAV6-GFP) or Cre (AAV6-GFP Cre) adenovirus vectors in Netrin-1fl/fl mice (left panel: green-GFP, red-TH; right panel: Cy-5-TH) (Scale bar, 1000 μm). Filled arrows indicate SN TH dopamine neurons.",
    "ncbi_link": "GFP: 
Cre: 2777477
Netrin-1: 18208"
  },
  {
    "caption": "(B) Representative images of TH and netrin-1 stainings by immunofluorescence (scale bar, 2000 μm) six weeks after the intranigral injection of CTL adenovirus vector (left panel) or Cre adenovirus vector (right panel), in the midbrain (substantia nigra (SN) and ventral tegmental area (VTA) of Netrin-1fl/fl mice.",
    "ncbi_link": "Cre: 2777477
Netrin-1: 18208"
  },
  {
    "caption": "(C) Quantification of fluorescence intensity of TH-positive neurons, in the substantia nigra (SN) (left), and fibres, in the striatum (right), six weeks after adenovirus vector injection, in Netrin-1fl/fl mice. Bars and error bars represent the mean ± SEM. Statistical significance was determined by an unpaired t-test. *P < 0.05; **P< 0.01. N=3 each group.",
    "ncbi_link": "Netrin-1: 18208"
  },
  {
    "caption": "(D) Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labelling (TUNEL) reactivity in the SN after Cre and control adenovirus vector injection, in Netrin-1fl/fl mice (Scale bar, 50μm). The apoptotic index is expressed as a percentage of TUNEL positive neurons out of the total number of TH-positive neurons. Bars and error bars represent the mean ± SEM. Statistical significance was determined by an unpaired t-test. **P< 0.01. N=3 each group.",
    "ncbi_link": "Cre: 2777477
Netrin-1: 18208"
  },
  {
    "caption": "(F) Immunoblot of SN lysates from netrin-1 wild type (WT) and netrin-1 conditional KO mice (left upper panel). Densitometry band quantification of cleaved receptor over full length receptor ratio (lower right panel). We randomly selected 2 mice from each group for immunoblot analysis. N=3 independent experiments. Bars and error bars represent the mean ± SEM. Statistical significance was determined by an unpaired t-test. *P < 0.05; P**< 0.01.",
    "ncbi_link": "netrin-1: 18208"
  },
  {
    "caption": "(A) Representative images of TH+ dopamine neurons and fibers staining by immunofluorescence, in the SN and the striatum (Str) 6 weeks after CTL (AAV6-GFP); Cre (AAV6-GFP Cre); sh DCC (AAV6-GFP Cre + Sh-DCC) and shUNC5B (AAV6 GFP Cre + Sh-UNC5B) injection into the SN of Netrin-1fl/fl mice. (Scale bar, 2000 µm). (B) Quantification of TH fluorescent intensity in the SN (upper bar graph) and striatum (Str) of Netrin-1fl/fl mice (lower bar graph). Data are shown as mean + SEM. Statistical significance was determined by an unpaired t-test. N = 3 each group. Tukey post hoc analysis after one-way ANOVA *P < 0.05, **P <0.01, N.S., not significant.",
    "ncbi_link": "GFP: 
Cre: 2777477
DCC: 13176
Netrin-1: 18208
UNC5B: 107449"
  },
  {
    "caption": "(C) DCC depletion mitigates netrin-1 depletion-induced apoptosis in Netrin-1fl/fl mice. TH-positive cell loss was assessed by TUNEL assay in the SN. Upper panel, TUNEL (red) and TH (Cy5-white) (Scale bar, 50 µm). Apoptotic index (bar graph, bottom panel) expressed as a percentage of TUNEL positive neurons out of the total number of TH-positive neurons. N = 3 each group. Bars and error bars represent the mean ± SEM. Statistical significance was determined using a one-way ANOVA followed by post hoc Tukey test for multiple group comparison. *P < 0.05; P**< 0.01.",
    "ncbi_link": "DCC: 13176
Netrin-1: 18208
netrin-1: 18208"
  },
  {
    "caption": "(F) TH staining by immunohistochemistry (Scale bar, 2000µm) in the SN (left) and striatum (right) of WT and SNCA Tg mice, 6 days after treatment.",
    "ncbi_link": "SNCA: 6622"
  },
  {
    "caption": "(A) Netrin-1 gene expression profiling by array of substantiae nigrae from PD and non-PD (Control) patients using the GEO dataset GSE7621 that has a total of 25 samples (n=9 control and n=16 PD cases). Unpaired t-test, ***P < 0.0005, Mean ± SD are shown.",
    "ncbi_link": "Netrin-1: 9423"
  },
  {
    "caption": "(D)  EI24  knockout promotes the activation of IRE1, but not  PERK or ATF6. Control (sgGFP) and EI24 knockout (sgEI24) HeLa cells were treated with 4 μM  TM for the indicated  times. Protein expression  was analyzed by immunoblotting.",
    "ncbi_link": "GFP: 
EI24: 9538"
  },
  {
    "caption": "(G) Expression of  Flag-EI24 in EI24 knockout cells inhibits IRE1 activity. Flag-Metap2 served as the control. Cells transfected with the indicated cDNAs were treated with or without 4 μM TM for 2 hr.  Protein expression  was analyzed by  immunoblotting.",
    "ncbi_link": "EI24: 9538"
  },
  {
    "caption": "(B)  EI24 persistently  localizes on the ER regardless of the presence or absence of ER stress. HeLa cells stably expressing  Flag-EI24 were treated with or without 4 μM  tunicamycin  (TM) for 2 hr. Colocalization  of EI24 with ER was analyzed. KDEL-mCherry, ER marker. Scale bar, 10 μm.",
    "ncbi_link": "Flag: 
EI24: 9538"
  },
  {
    "caption": "(D) The C-terminus of EI24 is required for IRE1 binding. HeLa cells transfected with the indicated EI24 mutants were treated as in (B), after which protein-protein interactions  were analyzed by immunoprecipitation (IP). The star represents IgG light chains. (E) The C-terminus of  EI24 binds  to IRE1 in a persistent fashion. HeLa cells transfected with the indicated EI24 domains were treated as in (B). Protein-protein interactions  were analyzed by  IP. The star represents IgG light chains. (",
    "ncbi_link": "EI24: 9538"
  },
  {
    "caption": "(I) EI24  overexpression cannot prevent the activation of the phospho-mimicking (3SE)  IRE1 mutant. Wild-type and IRE1 3SE knock-in HeLa  cells were transfected with empty vector or Flag-EI24. Transfected cells were treated as in (B). Protein expressions were analyzed by immunoblotting.",
    "ncbi_link": "Flag: 
EI24: 9538
IRE1: 2081"
  },
  {
    "caption": "(L) Expression of full-length  EI24 or the △TM34 or △C mutant in EI24  knockout  HeLa  cells for comparison of their functions. HeLa cells transfected with the indicated EI24 mutants were treated as in (B). Protein expressions were analyzed by immunoblotting.",
    "ncbi_link": "EI24: 9538"
  },
  {
    "caption": "(B, C)  EI24 knockout causes resting-state  ER calcium  reduction (B) and cytosolic calcium elevation (C) under ER  stress. Control (sgGFP) and EI24 knockout (sgEI24)  HeLa cells were first perfused in  TM-free buffer, and switched to the buffer containing 4 μM  TM to induce ER stress where indicated. Resting state calcium levels in the  ER (B) and cytosol (C) with or without  TM are displayed in columns. Data information: N = 20 cells for one replicate. Data are mean ± SEM (n = 3 technical replicates). ns, no significant difference; ***P < 0.001; two-tailed Student's t-test.",
    "ncbi_link": "GFP: 
EI24: 9538"
  },
  {
    "caption": "(G) Knockdown of IP3R1 prevents  calcium mobilization  from the  ER to the  cytosol. The measurements were similarly performed as in (E), and were from the same batch of cells. Data information: N = 20 cells for one replicate. Data are mean ± SEM (n = 3 technical replicates). ns, no significant difference; ***P < 0.001; two-tailed Student's t-test.",
    "ncbi_link": "IP3R1: 3708"
  },
  {
    "caption": "(I) Wild-type  EI24, but not the TM34- or C-terminus-deleted mutant, preserves  ER calcium  stores in EI24 knockout cells. The measurements were similarly performed as in (E), and were from the same batch of cells. Data information: N = 20 cells for one replicate. Data are mean ± SEM (n = 3 technical replicates). ns, no significant difference; ***P < 0.001; two-tailed Student's t-test.",
    "ncbi_link": "EI24: 9538"
  },
  {
    "caption": "(B) Knockdown of IP3R1 prevents ER stress-induced apoptosis in EI24 knockout cells. Cells were cultured with or without 4 μM TM for 8 hr. Percentages of early apoptotic cells were measured by  flow cytometry. Data information: N ≈ 10000 cells for one biological replicate. Data are mean ± SEM (n = 3 or 4 biologically independent replicates). ns, no significant difference; ***P < 0.001; two-tailed Student's t-test",
    "ncbi_link": "EI24: 9538
IP3R1: 3708"
  },
  {
    "caption": "(D) Knockdown of  IP3R1 prevents ER stress-induced apoptosis. Cells were treated with 4 μM TM  for the indicated times. Protein expressions were analyzed by  immunoblotting.",
    "ncbi_link": "IP3R1: 3708"
  },
  {
    "caption": "(F-H) Reintroduction of full-length EI24, but not the TM34- or C-terminus-deleted mutant (F, G) or the C-terminus alone (H), inhibited ER stress-induced apoptosis in EI24  knockout cells. Cells treated with or without  TM were analyzed for apoptosis  by  flow cytometry (F, H) or by  immunoblotting (G). Arrows in (H) denote decreased or increased apoptotic levels. Data information: N ≈ 10000 cells for one biological replicate. Data are mean ± SEM (n = 3 or 4 biologically independent replicates). ns, no significant difference; ***P < 0.001; two-tailed Student's t-test for F), one-tailed Student's t-test for (H).",
    "ncbi_link": "EI24: 9538"
  },
  {
    "caption": "(A-B) Levels of miR-122 in Huh7 cells and released EVs either untreated (Fed) or subjected to starvation for metabolites including amino acids for 16h (Starved). miR-122 signals were detected by Northern blotting and position of the 32P-labelled Oligos that served as size markers are shown in the lane (A). U6 snRNA was used as loading control.",
    "ncbi_link": "U6: 
miR-122: 406906"
  },
  {
    "caption": "(A-B) Levels of miR-122 in Huh7 cells and released EVs either untreated (Fed) or subjected to starvation for metabolites including amino acids for 16h (Starved). Cellular CAT-1 levels were measured by qRT-PCR using GAPDH mRNA as control (B). A scheme of experiment is shown in the top panel in B.",
    "ncbi_link": "GAPDH: 
CAT-1: 6541"
  },
  {
    "caption": "(C-D) Cellular and extracellular levels of different miRNAs and EV associated proteins in Fed and Starved Huh7 cells. Relative changes in cellular and extracellular levels (EV associated) of miR-122 and miR-24 in Fed or 8h Starved Huh7 cells were quantified by qRT-PCR and plotted (mean+/- s.e.m., n=3). Levels of individual miRNAs in Fed condition were taken as unit. Fold change (with SD) in the cellular level of all miRNAs and pre-miR-122 measured were shown in the bottom panel (C). Cellular miRNA levels were normalized against U6 snRNA.",
    "ncbi_link": "U6: 
miR-122: 406906
miR-24: 407013///407012"
  },
  {
    "caption": "(E) Effect of GW4869 treatment on cellular miRNA content in Fed and Starved cells. Levels of miRNAs were measured by real-time quantification and normalized against U6 snRNA. Mean data are from three independent experiments. DMSO treatment was used as control for GW4869 treated cells.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "(F) CAT-1 and Aldolase mRNA expression in DMSO or GW4869 treated starved Huh7 cells. qRT-PCR techniques was adopted for quantification using 18S rRNA values for normalization (mean +/- s.e.m., n=3).",
    "ncbi_link": "18S: 
Aldolase: 229///226
CAT-1: 6541"
  },
  {
    "caption": "(G) Effect of siSMPD2 treatment on miR-122 content of EVs from Fed and Starved Huh7 cells. EVs from Fed and Starved Huh7 cells, depleted for SMPD2, were isolated and miR-122 content were measured by qRT-PCR and normalized against protein content of EVs. Fold change in EV associated miR-122 levels upon starvation both for control and siSMPD2 treated cells were shown above the respective bars.",
    "ncbi_link": "miR-122: 406906
SMPD2: 6610"
  },
  {
    "caption": "(H) Effect of siSMPD2 treatment on CAT-1 mRNA content (left panel) and miR-122 levels (right panel) in Huh7 cells. RNAs, from Fed and Starved Huh7 cells, depleted for SMPD2, were isolated and miR-122 and CAT-1 mRNA contents were measured by qRT-PCR. miR-122 contents were normalized against U6 snRNA. GAPDH mRNA was used for normalization of CAT-1 mRNA levels (mean +/- s.e.m., n=3). miR-122 levels for siCon treated cells (Fed and Starved) were considered as units.",
    "ncbi_link": "GAPDH: 
U6: 
miR-122: 406906
CAT-1: 6541
SMPD2: 6610"
  },
  {
    "caption": "(I-J) A schematic representation of the experiment to separate Extracellular Vesicles (EVs) on OptiPrep@ density gradient (left panel). Densities of fractions 1-10 are plotted and a best-fit curve is drawn (right upper panel). CD63 levels in individual fractions of Fed and Starved cells were detected by western blots to confirm the presence of exosomes of Fed and Straved cells (right lower panel). Mean Ct values of miR-122 in RNAs isolated from Exosome enriched (8-9) vs Non-exosomal (1-3) fractions were analyzed and plotted (J) (mean +/- s.e.m., n=3).",
    "ncbi_link": "miR-122: 406906"
  },
  {
    "caption": "(L) Effect of thapsigargain (TG) treatment of Huh7 cells on cellular and EV associated miR-122 level. A schematic representation of the experiment (upper panel). miR-122 levels were measured by qRT-PCR in total cellular RNA and in EVs released by the treated cells. Values were normalized either against U6 snRNA or protein content of EVs (mean+/- s.e.m., n=3) (lower panels) for cellular and EV associated RNA respectively.",
    "ncbi_link": "U6: 
miR-122: 406906"
  },
  {
    "caption": "(A) Relative amount of miRNAs bound to HuR that are immunoprecipitated either from Fed or Starved Huh7 cells. Immunoprecipitated materials were separated into two equal halves to do western blot analysis of HuR and relative quantification of associated miR-122 and miR-21 were done by quantitative RT-PCR (mean +/- s.e.m., n=3). GFP used as negative control to confer the specificity of the anti-HuR3A2 antibody in immunoprecipitating HuR. The miR-122 content in the GFP-antibody immunoprecipitated materials was too low to get detected reliably using the qRT-PCR.",
    "ncbi_link": "miR-122: 406906
miR-21: 406991"
  },
  {
    "caption": "(B-C) Effect of HuR depletion on cellular and EV content of miRNAs in Huh7 cells. Schemes of HuR depletion experiments in Huh7 cells (B). In siHuR treated cells, depletion of HuR was monitored by western blotting (mean+/- s.e.m., n=4)",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(B-C) Effect of HuR depletion on cellular and EV content of miRNAs in Huh7 cells. Relative levels of miRNAs were measured in EVs released from siCon or siHuR treated cells by qRT-PCR. Cellular miRNA contents were normalized against U6 snRNA. Levels of each miRNA in control siRNA (siCon) treated set were taken as unit. (C). CAT-1 and Aldolase mRNA levels of siHuR and siCon treated Fed Huh7 cells were quantified by qRT-PCR and normalized against GAPDH mRNA.",
    "ncbi_link": "GAPDH: 
U6: 
Aldolase: 229///226
HuR: 1994
CAT-1: 6541"
  },
  {
    "caption": "(D) Effect of HuR knockdown on cellular level of different miRNAs in starved Huh7 cells. Relative levels were estimated by real time qPCR, normalized with respect to U6 snRNA and plotted in the left panel. Levels of miR-122 in EVs of starved siHuR and siCon treated Huh7 cells were also measured by RT-PCR and plotted in the right panel (mean+/- s.e.m., n=3).",
    "ncbi_link": "U6: 
HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(E) Level of eIF-2a and its phosphorylated form, estimated by western blot using specific antibodies, in siCon or siHuR treated and starved Huh7 cell extracts. Western blot data of HuR confirm reduction of this protein upon siRNA treatment. CAT-1 and Aldolase mRNA levels were estimated by real time quantification and normalized against GAPDH level. Values of siCon treated samples were taken as unit (mean+/- s.e.m., n=3). In the right panel the relative quantity of phosphorylated eIF-2a measured by densitometry were plotted. Levels of p38 and phosphor-p38 levels in siCon and siHuR treated Starved Huh7 cells were detected by western blot.",
    "ncbi_link": "GAPDH: 
Aldolase: 229///226
HuR: 1994
CAT-1: 6541"
  },
  {
    "caption": "(F) Western blot analysis to detect the level of phosphorylated eIF-2a and eIF-4E-BP1 in lysates of Starved and HuR depleted Huh7 cells either transfected with ant-let-7a or anti-miR-122 oligos. miR-122 inactivation was monitored by measuring cat-1 level by qRT-PCR using GAPDH as control (mean+/- s.e.m., n=3). * denotes the phosphorylated eIF-4E-BP1. b-Actin was used as loading control. Relative levels of phosphorylated eIF-2a were measured by densitometric estimation of three independent measurements.",
    "ncbi_link": "GAPDH: 
HuR: 1994
miR-122: 406906
let-7a: 406881
cat-1: 6541"
  },
  {
    "caption": "(A) Northern blot of miR-122 in Huh7 cells expressing the Control and HA-HuR expression plasmids. The U6 was used for loading control. Position of the 32P-labelled Oligos, blotted to the membrane used for Northern blotting, served as size markers are shown in the M lane.",
    "ncbi_link": "U6: 
HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(B) Schematic representation of experiments done in Huh7 cells expressing HA-HuR (bottom). For control, pCIneo transfected Huh7 cells were used. Relative expression of HuR in transfected cells were analysed by western blot (top). b-actin blots were used as loading controls.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(C) Cellular and EV-associated miRNA levels were measured in Huh7 cells either expressing the pCIneo or HA-HuR expressing vectors by qRT-PCR (mean+/- s.e.m., n=5). Cellular miRNA levels were normalized against U6 snRNA.",
    "ncbi_link": "U6: 
HuR: 1994"
  },
  {
    "caption": "(E) Effect of HA-HuR expression on miRNA levels on EV and non-EV fractions of the culture supernatant collected from control and HA-HuR encoding plasmid transfected Huh7 cells. For isolation of non-EV fraction, supernatant obtained after removal of EVs by ultracentrifugation was used for RNA preparation (left panel) (mean+/- s.e.m., n=3). Effect of HuR expression on CD63, Alix and HuR levels in EVs. Extracts from EVs isolated from control or HA-HuR expressing Huh7 cells were western blotted for respective proteins (right panel).",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(F) Relative miR-122 levels in CD63 positive affinity purified EVs isolated from HA-HuR and pCIneo transfected Huh7 cells were quantified by qRT-PCR (mean+/- s.e.m., n=3). The levels of miR-122 were normalized against CD63 content of EVs.",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(G) Effect of GW4869 on EV associated content of three different miRNAs in HA-HuR expressing Huh7 cells quantified by qRT-PCR (mean+/- s.e.m., n=5). EVs from DMSO treated cells were used as control.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(H) A schematic representation of the experiment done to characterize EVs isolated from Huh7 cells expressing HA-HuR or pCIneo respectively by running OptiPrepTM density gradient (left panel) and western blotting for CD63 (right upper panel). Relative miR-122 levels in fractions 1-2 and 8-9 were compared by qRT-PCR (right lower panel).",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(I) Levels of apoptic cells in HA-HuR expressing Huh7 cells. Western Blot detection of apoptosis marker Cytochrome C was done (top) for EV associated and cellular fractions of HA-HuR and pCIneo (control) expressing Huh 7 cells respectively. Western blot for HA-HuR was done to analyse the expression of HA-HuR in EVs isolated from HA-HuR and pCIneo expressing Huh7 cells. CD63 and β-actin are used as loading control for EV associated fractions and cellular fractions respectively (upper panels). TUNEL assay of HA-HuR and pCIneo expressing and non-transfected Huh 7 cells was performed and representative pictures of HA-HuR and pCIneo expressing cells along with picture of non-transfected but DNase treated (positive control ) cells were compared (lower panels). Scale bar 50 µM.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(B) Change in miR-122 level in starved mouse liver. Endogenous miR-122 (left panel) and CAT-1 mRNA (middle panel) levels in mouse liver starved for 12h were quantified by qRT-PCR. miR-122 levels in the blood serum of corresponding animals were also measured (right panel). The Ct values of miR-122 and CAT-1 mRNA obtained for each individual animal liver and blood serum were plotted (mean+/- s.e.m., n=5).",
    "ncbi_link": "miR-122: 387231
CAT-1: 11987"
  },
  {
    "caption": "(F). Change in miR-122 level upon expression of HA-HuR in mouse liver. Endogenous miR-122 level in HA-HuR expression plasmid injected mouse liver were quantified by RT-PCR and compared against liver RNA samples collected from control (pCIneo injected) group of animals (mean+/- s.e.m., n=5).",
    "ncbi_link": "HuR: 15568
miR-122: 387231"
  },
  {
    "caption": "(G) Endogenous miR-122 target CAT-1 (left panel) and Aldolase (right panel) mRNA levels in HA-HuR or pCIneo (control) injected mouse liver were quantified by RT-PCR (mean+/- s.e.m., n=4).",
    "ncbi_link": "Aldolase: 230163///11674
HuR: 15568
miR-122: 387231
CAT-1: 11987"
  },
  {
    "caption": "(H) miR-122 levels in the blood serum of pCIneo (control) or HA-HuR expression plasmid injected mice were measured. The Ct values of miR-122 and CAT-1 and Aldolase mRNAs obtained for each individual animal liver and blood serum were plotted (mean+/- s.e.m., n=5).",
    "ncbi_link": "Aldolase: 230163///11674
HuR: 15568
miR-122: 387231
CAT-1: 11987"
  },
  {
    "caption": "(A) Time course experiment of HuR binding of miR-122 replaced from Ago2miRNPs. A schematic representation of in vitro miRNA binding assay of HuR (left panel). Equal amounts of recombinant HuR (rHuR), after indicated time of the miRNP interaction on FLAG-beads, were immunoprecipitated and HuR associated miR-122 levels were detected by qRT-PCR (right top panel). Ago2western blot detects its presence in the FLAG beads used in the assay and its absence in HuRimmunoprecipitated materials. HuRwestern blot was used to confirm its presence and quantification of its levels in the immunoprecipitated materials, at different time points (right bottom panel).",
    "ncbi_link": "miR-122: 406906"
  },
  {
    "caption": "(C) Coomassie stained gel picture denotes the purity of the recombinant HuR used in the assay. The same proteins were western blotted for HuR to show the specificity of the antibody used for immunoprecipitation. The recombinant P protein and N protein of Chandipura virus was used as negative control to confirm the specificity of 3A2 anti-HuR antibody.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(D) HuR western blot in middle right panel confirmed the presence of HuR and the truncated version of it in the immunoprecipitated materials. A representative domain picture of HuR and HuRΔIII are shown in the upper panel. Relative levels of HuR bound miR-122 were determined by qRT-PCR (mean+/- s.e.m., n=3) (middle left panel). Amount of miR-122 recovered from the immunoprecipitated materials were normalized against the amount of HuR or HuRΔIII present in the Immunoprecipitated materials. Ago2 western blot confirmed its presence in the FLAG beads used in the assay while Ago2 was not detected in HuR immunoprecipitated materials (bottom panel).",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(E) RNA electrophoretic mobility shift assay done with 32P-labeled synthetic miR-122 and recombinant HuR proteins. Radiolabelled miR-122 (100 fmol) was incubated with increasing concentration of FL-HuR (5-100nM) or HuRΔIII (100 nM) and gel shifting of miR-122 were marked by arrowhead. Position of the free probes is marked by an arrow. In the right panel, 1pmol of unlabelled TNF-alpha AU-rich element encoding synthetic RNA was used to compete with miR-122 binding of full length HuR. Amount of HuR or HuRΔIII used for gel shift assay were premeasured by densitometric estimation of coomassie stained gel bands from SDS page.",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(A) Subcellular distribution of HuR and Ago2 in Huh7 cells. Isotonic lysates of Huh7 cells transfected with HA-HuR expression or pCIneo control vector were analyzed on 3-30% OptiprepTM gradients for separation of organelles and localization of Ago2 and HuR were determined by western blotting analysis. Alix and Calnexin were used as markers of late endosome/MVB and ER respectively. Positions of specific organelle containing fractions were marked above the panels. * denotes the position of the high molecular weight HuR bands detected in the MVB fractions.",
    "ncbi_link": "HuR: 1994"
  },
  {
    "caption": "(C) Changes in relative level of miR-122 in the subcellular ER and MVB associated fractions of OptiprepTM gradients done with the cell lysates from pCIneo or HA-HuR expression vector transfected cells were measured by qRT-PCR (mean+/- s.e.m., n=5).",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(I) Full length and a truncated version of HA-HuR without the hinge region (graphical scheme in upper panel) was used to score the effect of deletion of hinge region on EV associated miR-122 content measured by qRT-PCR (bottom panel). Western blots to check expression of HuR and its truncated variants are also shown.\" * \" denotes the HA-HuR band (left lower panel). Data represented as mean+/- s.e.m., n=3.",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(J) Ubiquitination status of full length and a truncated version of HA-HuR without the hinge region between RRMII and RRMIII in Huh7 cells. HuR (full lenght or truncated version) were immunoprecipitated from cell lysates of Huh7 cells expressing these proteins and the immunoprecipitated materials were western blotted for HA-HuR and ubiquitination. Ubiquinitated HuR bands are marked by arrows. postion of non-ubiquitinated proteins were marked by arrowheads (upper panel). qRT-PCR based estimation of associated miRNA per unit of HA-HuR immunoprecipitated materials were estimated and normalized against respective protein levels quantified by densitometric quantification of western blots (lower panel). Data represented as mean+/- s.e.m., n=3. PCIneo transfected cells were used as control in immunoprecipitation reaction but no amplification of miR-122 were detected for HA immunoprecipitated materials from pCIneo tranfected cells.",
    "ncbi_link": "HuR: 1994
miR-122: 406906"
  },
  {
    "caption": "(A and B) qPCR analysis (n = 3) of BRCA1 mRNA (A) and pre-mRNA levels (B) in different cell cycle phases of HeLa cells.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(C) ChIP analysis (n = 3) of Pol II binding to BRCA1 promoter during G1 and S phases in HeLa cells. (D) ChIP analysis (n = 3) of Pol II-pSer2 binding to BRCA1 3'UTR during G1 and S phases in HeLa cells. Pol II-pSer2, phosphorylation of RNA Pol II CTD Ser2.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "Analysis of BRCA1 WT or 5q isoform RNA levels after the depletion of UPF1(n = 3) (O) or BRCA1 exon5 alternative splicing (n = 3) (AS) during the indicated cell cycle phases (P) by semi-quantitative RT-PCR (sqRT-PCR). Left, bar plot showing the concentration of BRCA1 isoforms in exon5 AS (O) or the ratio of BRCA1 WT isoform in exon5/11 AS (P the above is the representative DNA gel. Right, signal figure showing quantitative analysis of PCR products. RFU, relative fluorescence units. (P) HeLa cells were transfected with UPF1 siRNA, then BRCA1 WT and 5q isoform mRNA levels during the indicated cell cycle phases were analyzed by qPCR (n = 3). siNC, transfected with control siRNA. siUPF1, transfected with UPF1 siRNA.",
    "ncbi_link": "BRCA1: 672
UPF1: 5976"
  },
  {
    "caption": "Analysis of BRCA1 WT or 5q isoform RNA levels after the depletion of UPF1(n = 3) during the indicated cell cycle phases by semi-quantitative RT-PCR (sqRT-PCR). siNC, transfected with control siRNA. siUPF1, transfected with UPF1 siRNA.",
    "ncbi_link": "BRCA1: 672
UPF1: 5976"
  },
  {
    "caption": "(C and D) RNA pull-down assay shows RBM10 binding to BRCA1 exon5 (C) and exon11 (D) RNA in vitro.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(G and H) The BRCA1 protein (G) and mRNA levels (n = 3) (H) in 293T and RBM10-KD cells.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "(N and O) qPCR analysis (n = 3) of BRCA1 WT isoform mRNA level in exon11 AS during the indicated cell phases after depleting RBM10 in HeLa (N) and MCF-7 (O) cells.",
    "ncbi_link": "BRCA1: 672
RBM10: 8241"
  },
  {
    "caption": "(P) Results of western blot analyzing BRCA1 levels in HeLa and RBM10-KD cells in the indicated cell cycle phases.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "(A to D) Analysis of BRCA1 exon5 (A) and exon11 (C) AS by by semi-quantitative RT-PCR (sqRT-PCR) (n = 3), and analysis of BRCA1 exon5 (n = 3) (B) or exon11 (n = 3) (D) AS by minigene splicing reporter system after the depletion of RBM10. Bar plot shows the ratio of BRCA1 WT isoform in exon5/11 AS, the figure above is the representative DNA gel, the right is signal figure showing quantitative analysis of PCR products. RFU, relative fluorescence units.",
    "ncbi_link": "BRCA1: 672
RBM10: 8241"
  },
  {
    "caption": "(F) qPCR (n = 3) analyzing the WT and D11q isoform levels (exon11 AS) after RBM10 overexpression in 293T cells.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "(F) Analysis of BRCA1 exon5 AS by by sqRT-PCR (n = 3) in in G1/S phase of 293T cells treated with CDK2i. In (F) bar plot showing the ratio of BRCA1 WT isoform in exon5 AS, the above is the representative DNA gel. Right, signal figure showing quantitative analysis of PCR products. RFU, relative fluorescence units. Data are presented as mean ± s.d. in all qPCR.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(N) Analysis of BRCA1 exon5 AS by sqRT-PCR (n = 3), 293T cell was transfected with RBM10 S89D variant in G1 phase. In (N), bar plot showing the ratio of BRCA1 WT isoform in exon5 AS, the above is the representative DNA gel. Right, signal figure showing quantitative analysis of PCR products. RFU, relative fluorescence units. Data are presented as mean ± s.d. in all qPCR.",
    "ncbi_link": "BRCA1: 672
RBM10: 8241"
  },
  {
    "caption": "(O to Q) Phosphorylation at S89 of the indicated RBM10 variants (O), WT RBM10 in the indicated cell cycle phases (P), and WT/S89A mutant RBM10 after CDK2i treatment in G1/S phase (Q) were analyzed in 293T cells.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "(D) qPCR revealed the fold change (UPF1 knockdown vs control) of candidate genes in (C) with G1 down-expression depending on NMD (n = 3), the region above the dashed line means that depleting UPF1 increases the mRNA level of the candidate genes . Data are presented as mean ± s.d. in (D) two-sided unpaired t-test is used to determine the differences.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "γH2AX levels in RBM10-KD #4 cells under the treatments as indicated. Representative images were shown in (A). CPT, camptothecin. BLM, bleomycin. IR, ionizing radiation.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "Immunofluorescence analysis of γH2AX in RBM10-KD #4 cells complemented with either RBM10.",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "(H and I) HeLa cells were transfected with RBM10 or/with 53BP1 siRNA. Immunofluorescence analysis of γH2AX after CPT (H) and cisplatin (I) treatment.",
    "ncbi_link": "RBM10: 8241
53BP1: 7158"
  },
  {
    "caption": "Colony formation assay (n = 3) was performed in RBM10-depleted 293T cells treated with ionizing radiation (n = 3) (K)",
    "ncbi_link": "RBM10: 8241"
  },
  {
    "caption": "WB analysis (C) of the indicated genes or proteins in parental or IκBα KO HT29 cells obtained at pre-confluence or 7 days post-confluence. Bars represent mean values ± standard deviation of 3 technical replicates from 3 biological replicates performed.",
    "ncbi_link": "IκBα: 4792"
  },
  {
    "caption": "(H) Ifng protein and Ifng mRNA levels (n = 4/group) were determined by ELISA and quantitative PCR.",
    "ncbi_link": "Ifng: 15978"
  },
  {
    "caption": "(A) m6A dot blot assay using total RNA from NK92-siCTRL or NK92-siFTO cells.",
    "ncbi_link": "FTO: 79068"
  },
  {
    "caption": "(D) Western blotting for the detection of GZMB in NK92-siCTRL and NK92-siFTO cells after treatment with IL-2.",
    "ncbi_link": "FTO: 79068"
  },
  {
    "caption": "(B) Western blotting analysis. NK92-siCTRL or NK92-siFTO cells were incubated with 20 ng/ml IL-2 for 24 hours, washed, and cultured without IL-2 (IL-2 depletion) for the indicated times (n = 3). (C) A western blotting analysis of NK92+MOCK or NK92+FTO cells incubated with 20 ng/ml IL-2 for the indicated times was performed (n = 3). D",
    "ncbi_link": "FTO: 79068"
  },
  {
    "caption": "(C) m6A methylated RNA immunoprecipitation & quantitative PCR (MeRIP-qPCR) analysis using a m6A antibody in NK92-siFTO (upper) or NK92+FTO (lower) cells compared to NK92-siCTRL or NK92+MOCK cells.",
    "ncbi_link": "FTO: 79068"
  },
  {
    "caption": "(D) SOCS3 3'-UTR reporter assay using the AANAT reporter system. Plasmid information for the AANAT reporter system with or without the SOCS3 3'-UTR sequence (upper). Levels of Aanat protein (left) and Aanat mRNA (right) expression in HEK-293T cells co-transfected with plasmid-expressing AANAT reporter containing SOCS3 3'-UTR and siCTRL or siFTO.",
    "ncbi_link": "Aanat: 15
FTO: 79068
SOCS3: 9021"
  },
  {
    "caption": "(B) Relative mRNA expression levels of JAK/STAT target genes, IFNγ (n = 10 biological replicates), GZMB (n = 6 biological replicates) and PRF1 (n = 8 biological replicates) were determined by qPCR in CD56+-siCTRL or CD56+-siFTO cells.",
    "ncbi_link": "FTO: 79068
GZMB: 3002
IFNγ: 3458
PRF1: 5551"
  },
  {
    "caption": "(C) Western blotting of CD56+-siCTRL or CD56+-siFTO cells incubated with 20 ng/ml IL-15 and 20 ng/ml IL-21 for the indicated times was performed. Cells were lysed and analyzed by immunoblotting with antibodies to the indicated phosphorylated (p-) and total proteins (n = 2~3). Data are representative of three times independent experiments with similar results. The protein levels were expressed as the relative band density of the corresponding protein (lower).",
    "ncbi_link": "FTO: 79068
IL-15: 3600
IL-21: 59067"
  },
  {
    "caption": "(E) The images of the ventral bioluminescence (BLI) following the injection of NK92-TRC or NK92-shFTO cells.",
    "ncbi_link": "FTO: 79068"
  },
  {
    "caption": "(G) The survival curves after the injection of K562-Luc cells.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "(a-c) At 12-16 h post-transfection with GFP-LC3, NIH3T3 (a, b), MEF (b) or HCT116 (c) cells containing vector or the FLIP gene were treated with Hank's solution for 2-4 h (a) or with 2 μM rapamycin for 1-3 h (b, c). Subsequently, GFP-LC3 was detected using an inverted fluorescence microscope. Scale bar, 10 μm (a). The number of GFP-LC3-positive dots per cell was counted using a fluorescence microscope. Data are mean ± s.e.m.; n = 200-300 cells; three independent experiments; *P 0.01; **P 0.05) (b, c). At 60 h post-transfection with control siRNA or cFLIP siRNA, MEF cells were transfected with GFP-LC3 (c).",
    "ncbi_link": "FLIP: 
LC3: 
FLIP: 8837
LC3: 84557"
  },
  {
    "caption": "(e, f) NIH3T3 vector and NIH3T3-KSHV-vFLIP cells (e) or TREX-BCBL-Vector and TREX-BCBL-vFLIP cells (f) were treated with Hank's solution or 2 μM rapamycin for 2-4 h, respectively, followed by IB with anti-LC3 and anti-actin antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(g) At 12-16 h post-transfection with GFP-LC3, TREX-BCBL-vector and TREX-BCBL-vFLIP cells were treated with doxycycline for 24 h, followed by incubation with 2 μM rapamycin for an additional 12 h. GFP-LC3 was detected using an inverted fluorescence microscope. Scale bar, 5μm. The number of GFP-LC3-positive dots per cell was counted using a fluorescence microscope. Data are mean ± s.e.m.; n = 200-300 cells; three independent experiments; *P 0.01).",
    "ncbi_link": "LC3: 
vFLIP: "
  },
  {
    "caption": "(a) BCBL cells were used for immunoprecipitation (IP) with mouse IgG or anti-Atg3, followed by immunoblotting (IB) with anti-cFLIP antibody (left panel). NIH3T3-KSHV-vFLIP cells were used for IP with mouse IgG or anti-Flag antibody, followed by IB with anti-Atg3 antibody (right panel).",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(c) Schematic diagram of human Atg3 (top). N, amino terminus; FR, flexible region; C, carboxy terminus. At 48 h post-transfection with GST or GST-Atg3 along with Flag-vFLIP (left) or GST or GST-Atg3 along with GFP-LC3 (right), HEK293T cells were used for GST pulldown, followed by IB with the indicated antibodies.",
    "ncbi_link": "Atg3: 
vFLIP: 
Atg3: Q9NT62///Q9CPX6
LC3: 84557"
  },
  {
    "caption": "(d) Schematic diagram of KSHV vFLIP (top). The black boxes indicate the K-α2 and K-α4 peptides. At 48 h post-transfection with V5-Atg3 and either GST-vFLIP DED1 mutants (middle) or GST-vFLIP DED2 mutants (bottom), HEK293T cells were used for GST pulldown, followed by IB with anti-V5 antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(e) At 48 h post-transfection with GST, GST-Atg3, and either Flag-vFLIP or Flag-vFLIP mAtg3, HEK293T cells were used for GST pulldown, followed by IB with anti-Flag antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(f) At 48 h post-transfection with GST-Atg3 and GFP-LC3 along with increasing amount of Flag-vFLIP, HEK293T cells were used for GST pulldown, followed by IB with anti-GFP or anti-Flag antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(g) NIH3T3 vector and NIH3T3 vFLIP cells were treated with 2 μM rapamycin for 4 h and used for IP with anti-Atg3 antibody, followed by IB with anti-LC3 antibody. Finally, whole-cell lysates (WCLs) were used for IB with the indicated antibodies to show expression (a-g).",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(b) At 12-16 h post-transfection with GFP-LC3, doxycycline-treated TREX-BCBL vector, TREX-BCBL-vFLIP and TREX-BCBL-vFLIP mutant cells were incubated with or without 50 nM rapamycin for 6 days (top) or 2 μM rapamycin for 12 h (bottom). The percentage of cell death (trypan blue staining) and apoptosis level (annexin V staining) of rapamycin-treated cells was quantified as mean ± s.d. of three independent experiments. The number of GFP-LC3-positive dots per cell was counted using a fluorescence microscope. Data are mean ± s.e.m.; n = 200-300 cells; three independent experiments; *P<0.01.",
    "ncbi_link": "vFLIP: 
LC3: 84557"
  },
  {
    "caption": "(c) BCBL1 cells were transfected with control siRNA or Beclin1 siRNA and treated with or without rapamycin for 5 days. The percentage of cell death was determined by trypan blue staining. Data are mean ± s.e.m.; n = 200-300; three independent experiments; *P 0.05.",
    "ncbi_link": "Beclin1: 8678"
  },
  {
    "caption": "(d) TREX-BCBL vector and TREX-BCBL-vFLIP cells were mock-treated or treated with 50 nM rapamycin for the indicated periods of time. The results were quantified as mean ± s.d. of the combined results from three independent experiments; *P 0.001.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(e) HEK293 cells carrying KSHV or KSHVΔvFLIP were treated with 500 nM rapamycin for 6 days. The results were quantified as mean ± s.d. of the combined results from three independent experiments; *P 0.01. Trypan blue staining and a Beckman Coulter Z2 Particle Count and size analyzer (BC Z2 CS analyser) were used to determine cell death and cell growth analysis (b-e).",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(b) At 12-16 h post-transfection with GFP-LC3, TREX-BCBL vector and TREX-BCBL-vFLIP cells were treated with doxycycline for 24 h, followed by incubation with 30 μM of the TAT, K-α2 or K-α4 peptide (top left) or the TAT, C-α2, or C-α4 peptide (bottom left) for an additional 12 h. Subsequently, autophagy was quantified as means ± s.d. of the combined results from three independent experiments (2 μM rapamycin treatment was included as a control). TREX-BCBL vector and TREX-BCBL-vFLIP cells were treated with doxycycline for 24 h, followed by incubation with 0, 30, or 50 μM of the TAT, K-α2, or K-α4 peptide (top right) or the TAT, C-α2, or C-α4 peptide (bottom right) for an additional 12 h. Trypan blue staining was then used to determine cell death (as a percentage). Data are mean ± s.e.m.; n = 200-300; three independent experiments; *P 0.01; **P 0.05.",
    "ncbi_link": "LC3: 
vFLIP: "
  },
  {
    "caption": "(c) At 12-16 h post-transfection with GFP-LC3, TREX-BCBL vector and TREX-BCBL-vFLIP cells were treated with doxycycline for 24 h, followed by incubation with 30 μM of the TAT, K-α2 or K-α4 peptide (top left) or the TAT, C-α2, or C-α4 peptide (bottom left) for an additional 12 h. Subsequently, autophagy was quantified as means ± s.d. of the combined results from three independent experiments (2 μM rapamycin treatment was included as a control). TREX-BCBL vector and TREX-BCBL-vFLIP cells were treated with doxycycline for 24 h, followed by incubation with 0, 30, or 50 μM of the TAT, K-α2, or K-α4 peptide (top right) or the TAT, C-α2, or C-α4 peptide (bottom right) for an additional 12 h and GFP-LC3 puncta were subsequently detected using an inverted fluorescence microscope. Scale bar, 5 μm.",
    "ncbi_link": "vFLIP: 
LC3: 84557"
  },
  {
    "caption": "(e) TREX-BCBL-Vector and TREX-BCBL-vFLIP cells were treated with the K-α2 and the K-α4 (30 μM each) peptide for 12 h, followed by immunoblotting (IB) with anti-LC3 and anti-actin antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(a) At 16 h post-transfection with GST, GST-K-α2 or GST-K-α4 along with Flag-vFLIP (top) or Flag-cFLIPL (bottom), HEK293T cells were used for GST pulldown, followed by immunoblotting (IB) with anti-Flag or anti-FLIP antibody. Whole-cell lysates (WCLs) were used for IB with anti-GST, anti-Flag or anti-FLIP antibody.",
    "ncbi_link": "vFLIP: 
FLIP: 8837
FLIP: 8837///12633"
  },
  {
    "caption": "(b) At 16 h post-transfection with V5-Atg3 and Flag-vFLIP with increasing amounts of GST-K-α2 or GST-K-α4, HEK293T cells were used for GST pulldown, followed by IB with anti-Flag or anti-V5 antibody or for immunoprecipitation (IP) with anti-V5 antibody, followed by IB with anti-Flag antibody. WCLs were used for IB with anti-GST, anti-Flag or anti-V5 antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(c) At 12-16 h post-transfection with GST-Atg3 along with Flag-vFLIP (first), Flag-cFLIPS (second), or HA-LC3 (third) with increasing amounts of the K-α2+K-α4 peptides (top three panels) or C-α2+C-α4 peptides (bottom panel), HEK293T cells were used for GST pulldown, followed by IB with anti-Flag or anti-HA antibodies. WCLs were used for IB with anti-GST and anti-Flag antibody.",
    "ncbi_link": "LC3: 
vFLIP: 
cFLIP: 8837"
  },
  {
    "caption": "(d) At 12-16 h post-transfection with Flag-vFLIP, HA-LC3 and V5-Atg3, HEK293T cells were treated with increasing amounts of the K-α2+K-α4 peptides and used for IP anti-V5 antibody, followed by IB with anti-Flag or anti-HA antibody. WCLs were used for IB with anti-V5, anti-HA and anti-Flag antibody.",
    "ncbi_link": "vFLIP: "
  },
  {
    "caption": "(A-B) Mitochondria isolated from (A) hTim8aKO HEK cells with and without hTim8aFLAG re-expression, or (B) hTim8bKO HEK cells with and without hTim8bFLAG re-expression were compared to mitochondria isolated from control HEK293 cells by SDS-PAGE and immunoblot. Protein expression of the hTim8 protein was induced with tetracycline (Tet) for the indicated time. Representative of n=2 biological replicates.",
    "ncbi_link": "FLAG: 
Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "Affinity enrichment mass spectrometry. Mitochondria isolated from (C) hTim8aKO HEK cells expressing hTim8aFLAG, (D) hTim8bKO HEK cells expressing hTim8bFLAG, (E) hTim8aMUT SH cells expressing hTim8aFLAG, (F) hTim8bKO SH cells expressing hTim8bFLAG were treated with DSP crosslinker prior to immunoprecipitation with anti-FLAG resin. The log2 fold change in mean LFQ intensity is plotted against unpaired Student's t-test p-value (n=3 biological replicates). Curve indicates significantly enriched proteins. FDR<0.01; (C) s0=5.5, (D) s0=4.5, (E) s0=2, (F) s0=5, Functional annotations manually curated and coloured: TIMM family proteins (purple), Complex I subunits and assembly factors (orange), Complex IV subunits and assembly factors (green), MIA import substrates (blue), significantly enriched (black).",
    "ncbi_link": "FLAG: 
Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "Changes in protein abundance of hTim8a and hTim8b interactors in mitochondria isolated from (B) hTim8aKO HEK and hTim8bKO HEK, or (C) hTim8aMUT SH and hTim8bKO SH cells; determined by quantitative mass spectrometry as published in Quadrants are labelled with 8a/8b ↑ or ↓ to indicate the increase or decrease of protein abundances in each knock-out cell line. The log2 fold change in mean LFQ intensity between knock-out and control cells is plotted on each axis. Lines indicate fold change in abundance of ±1.5. n=3 biological replicates for each cell line. Functional annotations manually curated and coloured: TIMM family proteins (purple), Complex I subunits and assembly factors (orange), Complex IV subunits and assembly factors (green), MIA import substrates (blue), significantly altered (black).",
    "ncbi_link": "Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "(B-C) Mitochondria isolated from (B) COX17MUT HEK and (C) COX17KO SH cells were analysed by quantitative mitochondrial proteomics relative to control cells. The log2 fold change in mean LFQ intensity is plotted against unpaired Student's t-test p-value (n=3 biological replicates). Curve indicates significantly altered proteins; FDR<0.05; s0=0.5. Functional annotations manually curated and coloured: Complex I subunits and assembly factors (orange), Complex II subunits and assembly factors (yellow), Complex III subunits and assembly factors (red) Complex IV subunits and assembly factors (green), Complex V subunits and assembly factors (pink), TIMM family proteins (purple), significantly altered (black).",
    "ncbi_link": "COX17: 10063"
  },
  {
    "caption": "(D) Mitochondria isolated from control cells, COX17MUT HEK and COX17KO SH cells were analysed by BN-PAGE and immunoblotting with the indicated antibodies. COX4I1-containing complexes indicated as SC: Respiratory supercomplex, CIII2+CIV: Complex III2-Complex IV complex, CIV2: Complex IV dimer, CIV: mature Complex IV, and S2*: COX4I1-containing S2 subcomplex. Representative of n=2 biological replicates.",
    "ncbi_link": "COX17: 10063"
  },
  {
    "caption": "(F) Intact cells or mitochondria isolated from hTim8bKO HEK and control HEK293 cells were subject to ICP-MS analysis to measure copper (Cu) and iron (Fe) content. Abundance is shown as mean ±S.D for metal content per gram of protein. Significance determined by unpaired Student's t-test (n=3 biological replicates). **, p<0.01; 'ns' indicates not significant, p>0.05.",
    "ncbi_link": "Tim8b: 26521"
  },
  {
    "caption": "(A) hTim8aKO HEK, hTim8bKO HEK and control HEK293 cells were pulsed with [35S]-Met/Cys for 2 h in the presence of anisomycin and chased for the indicated times. Isolated mitochondria were analysed by SDS-PAGE, auto-radiography and immunoblot. n=1 biological replicates.",
    "ncbi_link": "Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "[35S]-COX6C and [35S]-COX7C were incubated with mitochondria isolated from (B) hTim8aMUT SH control SH-SY5Y Import proceeded in the presence or absence of mitochondrial membrane potential (ΔΨ) for the indicated times. Samples were analysed by BN-PAGE and autoradiography. CBB = Coomassie brilliant blue staining. Representative of n=2 biological replicates.",
    "ncbi_link": "Tim8a: 1678"
  },
  {
    "caption": "[35S]-COX6C and [35S]-COX7C were incubated with mitochondria isolated from (C) hTim8bKO HEK and control HEK23 cells. Import proceeded in the presence or absence of mitochondrial membrane potential (ΔΨ) for the indicated times. Samples were analysed by BN-PAGE and autoradiography. CBB = Coomassie brilliant blue staining. Representative of n=2 biological replicates.",
    "ncbi_link": "Tim8b: 26521"
  },
  {
    "caption": "(F) Mitochondria isolated from control, hTim8aMUT SH and hTim8bKO HEK cells were analysed by BN-PAGE and immunoblotting. COX4I1-containing complexes indicated as SC: Respiratory supercomplex, CIII2+CIV: Complex III2-Complex IV complex, CIV2: Complex IV dimer, CIV: mature Complex IV, and S2*: COX4I1-containing S2 subcomplex. Levels of COX4I1 present in subcomplex (*) was quantified as mean ±S.D percentage of COX4I1 present in mature Complex IV (CIV) for each cell line. Significance determined by unpaired Student's t-test (hTim8bKO HEK n=6 biological replicates; hTim8aMUT SH n=4 biological replicates). **, p<0.01.",
    "ncbi_link": "Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "(B-C) Profile plots of iBAQ intensity for Complex IV subunits across the complexome profile of mitochondria isolated from (B) hTim8aMUT SH and control SH-SY5Y cells; and (C) hTim8bKO HEK and control HEK293 cells. Subunits are plotted by Complex IV module and iBAQ intensity relative to the maximum intensity of plotted subunits. Solid line indicates subunits from control cells, dashed line from knock-out cells. Complex IV assemblies are indicated as SC: Respiratory supercomplex, CIII2+CIV: Complex III2-Complex IV complex, CIV: mature Complex IV, and S2*: COX4I1-containing S2 subcomplex. Representative of n=2 biological replicates. Data presented as iBAQ intensity, normalised as in (A) and expressed as a ratio of the maximum iBAQ intensity.",
    "ncbi_link": "Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "(A) Mitochondria isolated from hTim8aMUT SH cells with and without hTim8bFLAG expression compared to mitochondria from control SH-SY5Y cells were analysed by SDS-PAGE and immunoblotting. Amount of protein after 12 h induction (lanes 4 and 10) was quantified as mean ±S.D percentage of control SH-SY5Y mitochondria. Significance determined by unpaired Student's t-test (n=3 biological replicates). *, p<0.05; **, p<0.01; ***, p<0.001; ****,p<0.0001; 'ns' indicates not significant, p>0.05.",
    "ncbi_link": "FLAG: 
Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "(C) Mitochondria isolated from hTim8aMUT SH cells with and without hTim8bFLAG expression compared to mitochondria isolated from control SH-SY5Y cells analysed by BN-PAGE and immunoblotting. COX4I1-containing complexes are indicated as SC: Respiratory supercomplex, CIII2+CIV: Complex III2-Complex IV complex, CIV2: Complex IV dimer, CIV: mature Complex IV, and S2*: COX4I1-containing S2 subcomplex. Amount of COX4I1 present in mature monomeric Complex IV (CIV) was quantified as mean ±S.D percentage of control SH-SY5Y mitochondria. Significance determined by unpaired Student's t-test (n=3 biological replicates). **, p<0.001; ***, p<0.001; 'ns' indicates not significant, p>0.05.",
    "ncbi_link": "FLAG: 
Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "(D) Mitochondria isolated from hTim8bKO HEK cells with and without hTim8aFLAG expression compared to mitochondria isolated from control HEK293 cells by BN-PAGE. hTim8aFLAG expression induced by tetracycline for 8 h. Native protein complexes detected by immunoblot. COX4I1-containing complexes by immunoblot indicated as SC: Respiratory supercomplex, CIII2+CIV: Complex III2-Complex IV complex, CIV2: Complex IV dimer, CIV: mature Complex IV, and S2*: COX4I1-containing S2 subcomplex. Amount of COX4I1 present in mature monomeric Complex IV (CIV) was quantified as mean ±S.D percentage of control HEK293 mitochondria. Significance determined by unpaired Student's t-test (n=3 biological replicates). **, p<0.01; 'ns' indicates not significant, p>0.05.",
    "ncbi_link": "FLAG: 
Tim8a: 1678
Tim8b: 26521"
  },
  {
    "caption": "A Immunofluorescence staining   of KANK1  (red) and  α-tubulin (blue) in Strep-GFP-CEP170B  knock-in HeLa  cells. Lower panels show enlargements of the peripheral (1) and central (2) cortical  regions boxed in the upper panels. Data information: Scale bars, 5 μm.",
    "ncbi_link": "GFP: 
CEP170B: 283638"
  },
  {
    "caption": "C Immunofluorescence staining  of KANK1  in Strep-GFP-CEP170B  knock-in HeLa  cells treated with nocodazole. Lower panels show enlargements of boxed areas in the upper panels. D Immunofluorescence staining  of CEP170B  and α-tubulin in MCF7  cells. Lower panels show enlargements of boxed areas in the upper panels. Data information: Scale bars, 5 μm.",
    "ncbi_link": "GFP: 
CEP170B: 283638"
  },
  {
    "caption": "G Immunofluorescence staining  of KANK1, KANK2, or  liprin-α1  in control Strep-GFP-CEP170B  knock-in HeLa  cell line or indicated knockout (KO) cell lines that were generated based on the parental Strep-GFP-CEP170B  knock-in HeLa  cell line. Data information: Scale bars, 5 μ",
    "ncbi_link": "GFP: 
CEP170B: 283638"
  },
  {
    "caption": "B Streptavidin pull-down assay with extracts of HEK293T  cells expressing Bio-GFP-tagged  liprin-α1 full length (FL) or its indicated fragments, analyzed by Western blotting with indicated antibodies. The Bio-GFP-tagged bait proteins were detected by IRDye® 680RD Streptavidin.",
    "ncbi_link": "GFP: 
liprin-α1: 8500"
  },
  {
    "caption": "D Streptavidin pull down  assay with extracts of HEK293T  cells expressing Bio-GFP-tagged wild-type (WT) liprin-α1 fragment N1 or its NR/AA mutant, analyzed by  Western blotting with indicated antibodies. The Bio-GFP-tagged bait proteins were detected by IRDye® 680RD Streptavidin. E Streptavidin pull down  assay with extracts of HEK293T  cells expressing Bio-GFP-tagged WT liprin-α1 N1 fragment or its NR/AA mutant (bait) together with GFP-CEP170B   (prey), analyzed by Western blotting with GFP  antibody.",
    "ncbi_link": "GFP: 
liprin-α1: 8500"
  },
  {
    "caption": "F Immunofluorescence staining  of  liprin-β1 in liprin-α1  KO HeLa  cells transiently transfected with mCherry-tagged liprin-α1  full length or its NR/AA mutant. G, H Averaged intensity distributions for WT or NR/AA versions of mCherry-liprin-α1 (G) and liprin-β1 (H) for the experiments shown in (F). Distance from the cell edge is shown on the horizontal axis. n = 25-29 cells from three technical replicates. Data represent mean ± SEM. Data information: Scale bars, 5 μm.",
    "ncbi_link": "mCherry: 
liprin-α1: 8500"
  },
  {
    "caption": "J, K Immunofluorescence staining  of α-tubulin  (blue) in  liprin-α1 KO/Strep-GFP-CEP170B  knock-in double-engineered HeLa  cell line transiently transfected with mCherry-tagged liprin-α1 FL (J), fragment N1 (K), or their NR/AA mutant counterparts (J, K). Data information: Scale bars, 5 μm.",
    "ncbi_link": "GFP: 
mCherry: 
CEP170B: 283638
liprin-α1: 8500"
  },
  {
    "caption": "A TIRF microscopy time-lapse images on the left show the accumulation of CEP170B  along the distal segments of MT  lattices in the cortical  region of Strep-GFP-CEP170B  knock-in HeLa  cell line transiently transfected with EB3-TagRFP. Representative kymographs   on the right show an MT  plus end undergoing very short alternating growth and shrinking episodes (corresponding to the one marked as \"1\" in the images; upper right panel) and an MT  plus end undergoing longer depolymerization followed by rescues (corresponding to the one marked as \"2\" in the images; bottom right panel ). Scale bars: horizontal, 2 μm; vertical, 30 s. Data information: Scale bars, 5 μm.",
    "ncbi_link": "GFP: 
RFP: 
CEP170B: 283638
EB3: 22924"
  },
  {
    "caption": "D Immunofluorescence staining  of CAMSAP2  (red) and  α-tubulin (blue) in HeLa  cells transiently transfected with GFP  control or GFP-CEP170B. Lower panels show enlargements of boxed areas. E Quantification of the length of CAMSAP2  stretches for the experiments shown in (D). n = 12 cells from three technical replicates. Data information: Unless otherwise stated, Data represent mean ± SD. *, P<0.05; **, P < 0.01; ***, P < 0.001; two-tailed t test. Scale bars, 5 μm.",
    "ncbi_link": "GFP: 
CEP170B: 283638"
  },
  {
    "caption": "C Immunofluorescence staining  of CAMSAP2  (green) and α-tubulin (red) in control or CEP170B  KO MCF7  monolayer. Left panels: basal plane; middle panels: apical plane; right panels: side view. D Immunofluorescence staining  of α-tubulin (red) in control CAMSAP3-GFP  knock-in  Caco-2 monolayer or CEP170B  KO/CAMSAP3-GFP  knock-in double engineered Caco-2 monolayer. Left panels: basal plane; middle panels: apical plane; right panels: side view. Data information: Scale bars: 5 μm",
    "ncbi_link": "GFP: 
CAMSAP3: 69697
CEP170B: 283638"
  },
  {
    "caption": "G Caco-2  cells were cultured in Matrigel  for 5 days, and subsequently treated with  Cholera toxin  for 12 hours. Phase-contrast images of thus  formed control or CEP170B  KO Caco-2 cysts  were shown. H, I Representative images and quantification of four categories of lumen  formation for experiments shown in (G). n = 100 cysts  from three technical replicates. J Quantification of the diameter of control and CEP170B  KO Caco-2 cysts. n = 30 cysts  from three technical replicates. Data information: Data represents the mean ± SD. ***, P < 0.001; two-tailed t test. Scale bars: 25 μm",
    "ncbi_link": "CEP170B: 283638"
  },
  {
    "caption": "A, TIRF  images of live KIF2A-GFP   or KIF2C-GFP  knock-in HeLa  cells transiently transfected with mCherry-KANK1  (A) Insets show enlargements of boxed areas. Data information: Scale bars: 5 μm.",
    "ncbi_link": "GFP: 
mCherry: 
KANK1: 23189
KIF2A: 3796
KIF2C: 11004"
  },
  {
    "caption": "Treatment of HeLa cells with DFP (1mM for 24 h) decreases levels of CHIP (n=8, biological replicates; ***p<0.001; paired t-test).   Treatment of HeLa cells with DFP (1mM for 24 h) leads to decreased levels of CHIP mRNA (n=3, biological replicates; *p<0.05; unpaired t-test).  ",
    "ncbi_link": "CHIP: 10273"
  },
  {
    "caption": "CHIP knockdown increases levels of SENP3 but not SENP5 in HeLa cells. Nsi or CHIPi (Nsi, non-specific siRNA; CHIPi, CHIP siRNA; concentration, 20 nM) was transfected into HeLa cells for 48 h. Lysate samples were blotted as indicated.   CHIP knockdown prevents the DFP-induced increase in SENP3 levels. Nsi, SENP3i or CHIPi (Nsi, non-specific siRNA; SENP3i, SENP3 siRNA; CHIPi, CHIP siRNA; siRNA concentration, 20nM) was transfected into HeLa cells for 48 h. Two days post-transfection the cells were treated with DFP for a further 24 h.  ",
    "ncbi_link": "SENP3: 26168
CHIP: 10273"
  },
  {
    "caption": "SENP3 knockdown abolishes the DFP-induced increase in LC3-II in HeLa cells. Nsi or SENP3i (I) was transfected into HeLa cells. Two days post-transfection the cells were treated with DFP for a further 24 h. Whole cell lysate samples were blotted as indicated (Nsi, non-specific siRNA; SENP3i, SENP3 siRNA; siRNA concentration, 20nM; DFP, 1mM for 24 h; values normalized to the control value; n=3, biological replicates; ***, p<0.001; N.S., not significant, p>0.05; paired t-test).",
    "ncbi_link": "SENP3: 26168"
  },
  {
    "caption": "Nsi or SENP3i (II) was transfected into HeLa cells with stable expression of mito-Keima grown on 6-well plates. Two days post-transfection the cells were treated with DFP (1mM; 24 h). Cells transfected with Nsi and treated with CQ (50μM; 24 h) in the absence or presence of DFP (1mM; 24 h) were included as a negative control for mitophagy induction. The images show overlaid fluorescence and transmitted light images of unfixed, live cells obtained using an EVOS-fl inverted LED fluorescence microscope (Red: mitophagic puncta; Scale bar, 100 μm). Histogram shows the percentages of mitophagic cells under 6 different conditions (n=3, biological replicates; ****, p<0.0001; Ordinary one-way ANOVA followed by Tukey's multiple comparisons test).",
    "ncbi_link": "SENP3: 26168"
  },
  {
    "caption": "SENP3 knockdown abolishes DFP-induced mitophagic autolysosomes. Nsi or SENP3i (I) together with mito-pHfluorin were transfected into HeLa cells in the absence or presence of DFP (24 h), and were analyzed using the mito-pHfluorin construct 72 h post-transfection (Red: mCherry-A or puncta indicating occurrences of mitophagy marked by white arrows; Green: SEP-A; Yellow: mitochondria labelled by mCherry-SEP-A; Magenta: SENP3; Scale bar, 10 μm; n=28 cells per condition from two individual experiments; **** p<0.0001; unpaired t-test).",
    "ncbi_link": "SENP3: 26168"
  },
  {
    "caption": "Fis1 knockdown abolishes DFP-induced LC3-II. Fis1 siRNA was introduced into HeLa cells for 48 h, and the cells were treated with DFP for further 24 h (Nsi, non-specific siRNA; Fis1i, Fis1 siRNA; siRNA concentration, 20nM; DFP, 1mM). Whole cell lysate samples were blotted as indicated. Values are presented as mean ± SEM and are normalized to the control value (n=3, biological replicates; **, p<0.01; paired t-test).",
    "ncbi_link": "Fis1: 51024"
  },
  {
    "caption": "Fis1 knockout abolishes DFP-induced LC3-II. Fis1+/+ or Fis1-/- cells were treated with DFP for 24 h. Whole cell lysate samples were blotted as indicated. Values are presented as mean ± SEM and are normalized to the control value (n=6, biological replicates; *, p<0.05; paired t-test).",
    "ncbi_link": "Fis1: 51024"
  },
  {
    "caption": "Fis1 knockdown prevents DFP-induced mitophagic autolysosomes. Nsi or Fis1i together with mito-pHfluorin were transfected into HeLa cells in the absence or presence of DFP (24 h), which were analysed using the mito-pHfluorin construct 72 h post-transfection (Red: mCherry-A or puncta indicating occurrences of mitophagy marked by white arrows; Green: SEP-A; Yellow: mitochondria labelled by mCherry-SEP-A; Blue: Fis1; Scale bar, 10 μm; n=25 cells per condition from three individual experiments; *** p<0.001; unpaired-t test).",
    "ncbi_link": "Fis1: 51024"
  },
  {
    "caption": "Flag-Fis1 is deSUMOylated by SENP3. SENP3 knockdown enhances Fis1 SUMOylation. Nsi or SENP3i was transfected into HEK293 cells expressing Flag-Fis1, His-SUMO-2 and Ubc9 for 48 h. His-pulldown and lysate samples were detected by immunoblotting for Flag, SENP3 or β-actin. Values are presented as mean ± SEM (n=3, biological replicates; * p<0.05; paired-t test).",
    "ncbi_link": "Flag: 
His: 
Fis1: 66437
SUMO-2: 59343
SENP3: 26168
Ubc9: 7329"
  },
  {
    "caption": "The SUMOylation status of Fis1 influences its mitochondrial localization. Flag-Fis1 WT, Flag-Fis1 SUMOylation deficient mutant K149R or Flag-Fis1-SUMO-2ΔGG was expressed in HeLa cells for 48 h. Whole cell lysates and cytosolic and mitochondrial fractions were prepared and blotted as indicated (the upper panel). Histograms (the right panel) show normalized levels of Flag-Fis1 WT or Flag-Fis1 K149R mutant associated with the cytosolic or mitochondrial fraction (Value are presented as mean ± SEM and are normalized to the control value; n=7, biological replicates; *, p<0.05; paired t-test).",
    "ncbi_link": "Flag: 
Fis1: 66437
SUMO-2: 59343"
  },
  {
    "caption": "The SUMOylation status of Fis1 may influence its association with the Endoplasmic Reticulum (ER). Flag-Fis1 WT, Flag-Fis1 SUMOylation deficient mutant K149R or Flag-Fis1-SUMO-2ΔGG along with GFP-Cb5 as an ER marker were expressed in HeLa cells for 48 h. Immunocytochemistry was then performed (Green: ER labelled by GFP-Cb5; Blue: different Flag-Fis1 forms; Scale bar, 10 μm)",
    "ncbi_link": "Flag: 
Fis1: 66437
SUMO-2: 59343"
  },
  {
    "caption": "Expressing a SUMOylation-deficient Fis1 mutant reverses the effect of SENP3 knockdown on DFP-induced LC3-II induction. pcDNA3, Flag-Fis1 WT or Flag-Fis1 K149R mutant was transfected into HeLa cells in which SENP3 was depleted using siRNA for 48 h (Nsi, non-specific siRNA; SENP3i, SENP3 siRNA (I); siRNA concentration, 20nM), and the cells were treated with DFP for a further 24 h (DFP, 1mM). Lysate samples were blotted as indicated.",
    "ncbi_link": "Flag: 
Fis1: 66437
SENP3: 26168"
  },
  {
    "caption": "SENP3 depletion does not abolish mitophagic puncta detected in HeLa cells expressing SUMOylation deficient CFP-Fis1 K149R in the presence of DFP. CFP-Fis1 WT or CFP-Fis1 K149R mutant were transfected into HeLa cells in which SENP3 was depleted using siRNA for 48 h, and the cells were treated with DFP for a further 24 h (Red: mCherry-A or puncta indicating occurrences of mitophagy marked by white arrows; Green: SEP-A; Cyan/blue: CFP-Fis1; Magenta, SENP3; Scale bar, 10 μm); Values are presented as mean ± SEM (n=21 cells per condition from two individual experiments; **** p<0.0001; unpaired t-test). Knockdown of SENP3 was further confirmed by immunoblotting (the lower right panel).",
    "ncbi_link": "CFP: 
Fis1: 66437
SENP3: 26168"
  },
  {
    "caption": "A, B: Quantitative RT-PCR results showing relative expression levels of mouse Cnot6 and Cnot6l in oocytes (GV and MII), somatic tissues, ES cells (A) and preimplantation embryos (B). n = 3 biological replicates",
    "ncbi_link": "Cnot6: 104625
Cnot6l: 231464"
  },
  {
    "caption": "C: Cumulative numbers of pups per female showing fertility of WT and Cnot6l-/- female mice. n = 5 females for each genotype",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "D: Representative images results of oocytes collected from oviducts of WT and Cnot6l-/- mice at 16 h after hCG injection. scale bar, 100 μm. Arrows indicate polar body-1 (PB1)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "E: Confocal microscopy results of oocytes collected from oviducts of WT and Cnot6l-/- mice at 16 h after hCG injection. scale bar, 20 μm. Arrows indicate spindle poles",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "F: Rates of PB1 emission and normal spindle formation in oocytes ovulated by WT and Cnot6l-/- female mice. The numbers of analyzed oocytes were indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "G: Quantification of preimplantation embryos derived from WT and Cnot6l-/- females that develop to the indicated stages after hCG administration and mated with adult WT males. The numbers of analyzed embryos are indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "H: Representative images of embryos collected from the oviducts or uteri of WT and Cnot6l-/- female at indicated time points after hCG administration. Scale bar, 100 μm. Data information: Error bars, s.e.m. **P < 0.01; ***P < 0.001 by two-tailed Student"s t test. n.s.: non-signif",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "A: Rates of germinal vesicle breakdown (GVBD) and PB1 emission in oocytes cultured in vitro. Fully-grown GV oocytes were collected from PMSG-primed (44 h) WT and Cnot6l-/- mice. PB1: polar body-1. Error bars, s.e.m. The numbers of analyzed oocytes were indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "B: Representative images of WT, Cnot6l-/- and Btg4-/- oocytes showing PB1 emission at 16 h after culture. Arrows indicate PB1. Scale bar, 100 μm",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "C: Representative images of chromosome spreads made from WT and Cnot6l-/- oocytes after 16 h of in vitro maturation culture. Immunofluorescent staining of topoisomerase II (TOP2) and the centromere antigen CREST were performed to indicate chromosome arms and centromeres, respectively. Numbers of paired sister chromatids are indicated. Scale bar, 5 μm",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "D: Percentage (%) of aneuploidy among in vitro cultured WT and Cnot6l-/- oocytes that have released PB1s. Error bars, s.e.m. *P < 0.05; ***P < 0.001 by two-tailed Student\"s t test. n.s.: non-significant. The numbers of analyzed oocytes were indicate",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "E: Rates of GVBD, PB1 emission, and normal spindle assembly in WT, Cnot6l-/- and Btg4-/- oocytes cultured in vitro. Error bars, s.e.m. ***P < 0.001 by two-tailed Student\"s t test. n.s.: non-significant. The numbers of analyzed oocytes were indicate",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "F: Confocal microscopy results showing spindle assembly in WT, Cnot6l-/- and Btg4-/- oocytes at metaphase I (MI) and metaphase II (MII). Scale bar, 20 μm",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "G: Pericentrin immunofluorescence showing MTOCs in cultured WT, Cnot6l-/- and Btg4-/- oocytes at MI and MII stages. Spindle and DNA were labeled by microtubule nucleation factor (TPX2) and DAPI, respectively. Scale bar, 20 μm",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "A: Live cell imaging results showing in vitro meiotic division of WT and Cnot6l-/- oocytes. Abbreviations: PM, prometaphase; MI, metaphase I; AI, anaphase I; TI, anaphase I-metaphase II transition; MII, metaphase II; PB1: polar body-1. Hours after released from GV arrest were indicated. Scale bar, 20 μm",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "B: Data represent the mean and standard deviations of mCherry-Securin fluorescence intensity in WT and Cnot6l-/- oocytes at each time point. Values from individual oocytes are normalized relative to that at 0 h after released from GV arrest. The numbers of analyzed oocytes were indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "C: SMC3 immunofluorescence showing cohesin on chromosomes of WT and Cnot6l-/- oocytes at 16 h after culture. Centromeres and DNA were labeled by CREST and DAPI, respectively. Scale bar, 5 μm",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "D: BUB3 immunofluorescence on chromosome spreads made from WT and Cnot6l-/- oocytes at 9.5 h after culture. More than 8 oocytes were observed for each genotype with similar results. Scale bar, 5 μm",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "E: PB1 emission rates in WT and Cnot6l-/- oocytes cultured with or without MPS1 inhibitor reversin (5 μm). Reversin is added at 9 hours after culture. Error bars, s.e.m. The numbers of analyzed oocytes were indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "A: Relative mRNA copy number dynamics in WT and Cnot6l-/- samples at the indicated stages. Error bars indicate values of the two biological replicates",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "B: Box plot showing gene expression levels of WT, Cnot6l-/- and Btg4-/- oocytes at the MII stage. Genes were divided into 10 bins according to their expression levels in the WT MII oocytes. The box indicates upper and lower quantiles, the thick line in the box indicate the median, and the whiskers represent 2.5th and 97.5th percentiles. ***P < 0.001 by two-tailed Student\"s t test. n.s.: non-signif",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "C: qRT-PCR results showing the relative expression levels of Cnot6l in oocytes collected from WT and Cnot6l-/- mice (Cnot6l-/-/WT). Error bars, s.e.m. ***P < 0.001 by two-tailed Student\"s t test. n = 3 biological repli",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "D: Scatter plot comparing transcripts between WT and Cnot6l-/- oocytes (at GV, MI and MII stages) and zygotes derived from these oocytes. Transcripts decreased or increased more than five folds in Cnot6l-/- oocyte samples were high-lighted with blue or red, respectively",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "F: Relative mRNA copy number dynamics of the three gene clusters in WT, Cnot6l-/- and Btg4-/- samples",
    "ncbi_link": "Btg4: 56057
Cnot6l: 231464"
  },
  {
    "caption": "Western blot results showing the levels of CPEB1 in WT and Cnot6l-/- oocytes at the indicated time points after meiotic resumption. Total proteins from 50 (A oocytes are loaded in each lane. DDB1 (A is blotted as a loading control. Experiments were performed three times with reproducible results; a representative result is shown",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "Western blot results showing the levels of CPEB1 in WT and Cnot6l-/- oocytes at the indicated time points after meiotic resumption. Total proteins fro 100 (B) oocytes are loaded in each lane α-tubulin (B) is blotted as a loading control. Experiments were performed three times with reproducible results; a representative result is shown",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "Immunofluorescenc of L-homopropargylglycine (HPG) showing the overall translation levels of MI and MII oocytes collected from WT and Cnot6l-/- mice. Scale bar, 20 μm. Error bars, standard deviations (n = 6 oocytes for each genotype). **P < 0.01, ***P < 0.001",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "quantification (D) of L-homopropargylglycine (HPG) showing the overall translation levels of MI and MII oocytes collected from WT and Cnot6l-/- mice. Scale bar, 20 μm. Error bars, standard deviations (n = 6 oocytes for each genotype). **P < 0.01, ***P < 0.001",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "E: Relative mRNA copy numbers of polysome-bound transcripts in WT and Cnot6l-/- oocytes at indicated stages. Error bars indicate values of the replicates",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "F: Scatter plot comparing polysome-bound transcripts between WT and Cnot6l-/- oocytes at GV, MI and MII stages, respectively. Transcripts decreased or increased more than five folds in Cnot6l-/- oocyte samples were high-lighted with blue or red, respectively",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "I: Quantitative RT-PCR results showing the relative levels of indicated transcripts in association with polysomes in WT and Cnot6l-/- oocytes at GV, MI and MII stages. Error bars, standard deviations (n = 3 biologica repeats)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "A: Presence of putative AREs (AUUUA) in transcripts of WT oocyte. Transcripts containing no ARE or transcripts containing 1 or more AREs were subdivided into frequency groups according to the log2 fold change (MII/GV) in WT oocytes",
    "ncbi_link": "ARE: "
  },
  {
    "caption": "B: Presence of putative AREs in oocyte transcripts stabilized by Cnot6l-/- knockout. Transcripts containing no ARE or transcripts containing 1 or more AREs were subdivided into frequency groups according to the log2 fold change (Cnot6l-/-/WT) at MII stage",
    "ncbi_link": "ARE: 
AREs: 
Cnot6l: 231464"
  },
  {
    "caption": "C: Co-IP results showing interaction of ZFP36L2 with CNOT6L and CNOT7. HeLa cells were co-transfected with plasmids expressing HA-ZFP36L2 and FLAG-CNOT6L/7 for 48 h before immunoprecipitation. Experiments were performed three times with reproducible results; a representative result is shown",
    "ncbi_link": "CNOT6L: 231464
ZFP36L2: 12193"
  },
  {
    "caption": "D: RNA immunoprecipitation results showing interaction of CNOT6L with indicated transcripts, with or without the presence of ZFP36L2. HeLa cells were co-transfected with plasmids expressing FLAG-ZFP36L2 and HA-CNOT6L for 48 h before immunoprecipitation using an anti-HA antibody. mRNAs recovered from the immunoprecipitates were subjected to qRT-PCR. Error bars, standard deviations (n = 3 biological repeats). ***P < 0.001 by two-tailed Student"s t",
    "ncbi_link": "CNOT6L: 231464
ZFP36L2: 12193"
  },
  {
    "caption": "fluorescence microscopy results (B) showing the translation activities of the Cnot6l 3\"-UTR (WT and CPE mutated) in GV- (maintained by 2 μM milrinone) or MII- (released from milrinone) arrested oocytes. GFP signal indicated translational activation of Cnot6l 3\"-UTR. An in vitro transcribed and polyadenylated mCherry mRNA was co-microinjected as a positive control. Scale b",
    "ncbi_link": "Cnot6l: 231464
CPE: 12877"
  },
  {
    "caption": "GFP signal indicated translational activation of Cnot6l 3\"-UTR. An in vitro transcribed and polyadenylated mCherry mRNA was co-microinjected as a positive co Relative intensity of GFP signa after normalization by mCherry signal in the same oocyte. Error bars, s.e.m. *P < 0.05; ***P < 0.001 by two-tailed Student\"s t test. n.s.: non-significant. The numbers of analyzed oocytes were indicate",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "fluorescence microscopy results (E) showing the expression of GFP-fused Cnot6l 3"-UTR in GV and MII oocytes with or without U0126 treatment (20 μM). Scale bar, 1",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "e expression of GFP-fused Cnot6l 3\"-UTR in GV and MII oocytes with or without U01 F: Relative intensity of GFP signa after normalization by mCherry signal in the same oocyte The numbers of analyzed oocytes were indicated (n)",
    "ncbi_link": "Cnot6l: 231464"
  },
  {
    "caption": "G: Rates of PB2 emission and normal spindle assembly in oocytes cultured with or without U0126. Fully grown GV oocytes were microinjected with mRNAs encoding CNOT6L, CNOT7 and/or BTG4 and are released from milrinone at 12 h after microinjection. Then the oocytes were further culture for 24 h with or without adding U0126 to the medium. Error bars, s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001 by two-tailed Student"s t test. n.s.: non-significant. The numbers of analyzed oocytes were indicate",
    "ncbi_link": "BTG4: 56057
CNOT6L: 231464
CNOT7: 18983"
  },
  {
    "caption": "A Representative siliques from wild-type (WT; Col-0), herk1, anj and herk1 anj plants prior to dehiscence. Siliques were placed on double-sided sticky tape and carpel walls separated from the replum to expose the developing seeds. Scale bar = 5 mm.",
    "ncbi_link": "anj: 836091
herk1: 823774"
  },
  {
    "caption": "B Developing seeds per silique in wild-type, herk1, anj and herk1 anj plants. Fully expanded siliques were dissected and photographed under a stereomicroscope. n = 15 (four independent experiments with at least three plants per line and five siliques per plant). Data presented are means ± SEM. *** p<0.001 (Student's t-test).",
    "ncbi_link": "anj: 836091
herk1: 823774"
  },
  {
    "caption": "C Percentage of pollen tubes with normal reception at the female gametophyte (black bars; representative image middle centre of figure) and with overgrowth (grey bars; representative image lower centre) as assessed by aniline blue staining. 15 self-pollinated stage 16 flowers from wild-type, herk1, anj and herk1 anj were analysed. Legend scale bars = 50 µm. *** p<0.001 (χ-square tests).",
    "ncbi_link": "anj: 836091
herk1: 823774"
  },
  {
    "caption": "D Aniline blue staining of pollen tube reception in reciprocal crosses between wild-type and herk1 anj plants with at least two siliques per cross. Legend as per (C). *** p<0.001 (χ-square tests).",
    "ncbi_link": "anj: 836091
herk1: 823774"
  },
  {
    "caption": "E,F Localisation of HERK1-GFP in the synergid cell from the pFER::HERK1-GFP construct in (F) and corresponding differential interference contrast (DIC) image in (E). White and red dotted lines delineate the egg cell and synergid cells, respectively. Data information : Scale bars = 50 µm. M, micropyle. Arrows, filiform apparatus.",
    "ncbi_link": "GFP: 
FER: 824318
HERK1: 823774"
  },
  {
    "caption": "G,H Localisation of ANJ-GFP in the synergid cell from the pANJ::ANJ-GFP construct in (H) and corresponding DIC image in (G). White and red dotted lines delineate the egg cell and synergid cells, respectively. Data information : Scale bars = 50 µm. M, micropyle. Arrows, filiform apparatus.",
    "ncbi_link": "GFP: 
ANJ: 836091"
  },
  {
    "caption": "A Localisation of HERK1, ANJ, LRE, FER and NTA in the synergid cell of wild-type (Col-0; WT), herk1 anj and lre-5 in unfertilised ovules, as shown by pFER::HERK1-GFP, pANJ::ANJ-GFP, pLRE::LRE-Citrine, pFER::FER-GFP and pMYB98::NTA-GFP. DIC and fluorescence images are shown, left to right, respectively. White and red dotted lines delineate the egg cell and synergid cells, respectively. Scale bars = 25 µm.",
    "ncbi_link": "Citrine: 
GFP: 
anj: 836091
ANJ: 836091
FER: 824318
herk1: 823774
HERK1: 823774
LRE: 6240393
lre-5: 6240393
NTA: 816249
MYB98: 827611"
  },
  {
    "caption": "B Localisation of NTA in the synergid cell of wild-type and herk1 anj plants before (upper panels) and after (lower panels) pollen tube arrival. In green, NTA localisation as shown by pMYB98::NTA-GFP fluorescence. In magenta, callose of the filiform apparatus and pollen tube stained with SR2200. From left to right, images shown are DIC, merged fluorescence images, and merged images of DIC and fluorescence. White and red dotted lines delineate the pollen tube and synergid cells, respectively. Scale bars = 25 µm. M, micropyle.",
    "ncbi_link": "GFP: 
anj: 836091
herk1: 823774
NTA: 816249
MYB98: 827611"
  },
  {
    "caption": "Profile of relative fluorescence intensity of NTA-GFP along the synergid cells of wild-type and herk1 anj ovules (C) before (virgin) and after (pollinated) pollen arrival. Data shown are means ± SEM, n = 25. *** p<0.001 (Student's t-test). FA, filiform apparatus.",
    "ncbi_link": "anj: 836091
herk1: 823774"
  },
  {
    "caption": "D Profile of relative fluorescence intensity of NTA-GFP along the synergid cells of wild-type and lre-5 ovules (D) before (virgin) and after (pollinated) pollen arrival. Data shown are means ± SEM, n = 25. *** p<0.001 (Student's t-test). FA, filiform apparatus.",
    "ncbi_link": "lre-5: 6240393"
  },
  {
    "caption": "A Representative images of ovules from wild-type (Col-0), herk1 anj, lre-5 and fer-4 20 hours after emasculation (HAE) displaying the mature female gametophyte structure. Images presented here are maximum intensity projections from confocal microscopy images across several z-planes of ovules stained as per [70]. Scale bars = 50 µm.",
    "ncbi_link": "anj: 836091
fer-4: 824318
herk1: 823774
lre-5: 6240393"
  },
  {
    "caption": "B Quantification of H2DCF-DA staining of ROS in ovules from wild-type, herk1 anj, lre-5 and fer-4 plants at 20 HAE. Categories are listed in the legend Ovules dissected from at least five siliques per line. *** p<0.001 (χ-square tests).",
    "ncbi_link": "anj: 836091
fer-4: 824318
herk1: 823774
lre-5: 6240393"
  },
  {
    "caption": "C Percentage of pollen tubes with normal reception at the female gametophyte (black bars) and displaying overgrowth (grey bars) in wild-type, herk1 anj, lre-5 and fer-4 plants, manually selfed at 20 HAE. Fertilisation events counted from at least three siliques per line. *** p<0.001 (Student's t-test).",
    "ncbi_link": "anj: 836091
fer-4: 824318
herk1: 823774
lre-5: 6240393"
  },
  {
    "caption": "D Co-immunoprecipitation of FER with HERK1-GFP in Arabidopsis seedlings expressing pFER::HERK1-GFP. Numbers indicate molecular weight marker sizes in kDa. Assays were performed twice with similar results. CBB refers to Coomassie Brilliant Blue staining of total proteins.",
    "ncbi_link": "GFP: 
FER: 824318
HERK1: 823774"
  },
  {
    "caption": "A A heatmap showing the differential miRNAs expression as determined by miRNA-seq in progerin-expressing cells relative to control cells, P< 0.05. Lowly expressed miRNAs were shown in blue, highly expressed ones in red.",
    "ncbi_link": "progerin: "
  },
  {
    "caption": "D The level of novel-miR-27, miR-3656 and miR-59 in HGPS patient cells (HGAFDFN003 p21 and HGAFDFN167 p19) versus control (CRL-1474 cells p28) was assessed by qPCR.",
    "ncbi_link": "miR-3656: 
miR-59: 
miR-27: 407019///407018"
  },
  {
    "caption": "HGAFDFN003 cells were transfected with anti-miR-ctrl, anti-miR-3656 or anti-miR-59 for 5 days, cells were subjected to SA-β-gal staining. The percentage of SA-β-gal positive cells was calculated.",
    "ncbi_link": "miR-3656: 
miR-59: "
  },
  {
    "caption": "HGAFDFN003 cells were transfected with anti-miR-ctrl, anti-miR-3656 or anti-miR-59 for 5 days, The percentage of the Ki67 positive cells was calculated by immunofluorescence (F).",
    "ncbi_link": "miR-3656: 
miR-59: "
  },
  {
    "caption": "HGAFDFN003 cells were transfected with anti-miR-ctrl, anti-miR-3656 or anti-miR-59 for 5 days The level of cyclin A2 and lamin B1 was detected by western blot (G).",
    "ncbi_link": "miR-3656: 
miR-59: "
  },
  {
    "caption": "Progerin-expressing CRL-1474 cells were transfected with anti-miR-ctrl or anti-miR-59 for 5 days. The percentage of SA-β-gal positive cells was calculated. Scale bars: 100 μm (H).",
    "ncbi_link": "miR-59: 
Progerin: "
  },
  {
    "caption": "Progerin-expressing CRL-1474 cells were transfected with anti-miR-ctrl or anti-miR-59 for 5 days. The percentage of the Ki67 positive cells was calculated by immunofluorescence (I).",
    "ncbi_link": "miR-59: 
Progerin: "
  },
  {
    "caption": "Progerin-expressing CRL-1474 cells were transfected with anti-miR-ctrl or anti-miR-59 for 5 days. The level of cyclin A2 and lamin B1 was detected by western blot (J).",
    "ncbi_link": "miR-59: 
Progerin: "
  },
  {
    "caption": "K The level of miR-59 was detected in 88- and 92-year-old cells versus 7-year-old cells was assessed by qPCR.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "L 7-year-old cells and 88-year-old cells were transfected with anti-miR-ctrl or anti-miR-59, the level of cyclin A2 and lamin B1 was detected.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "HGAFDFN003 cells were transfected with anti-miR-ctrl or anti-miR-59 for 5 days, the mRNA level of miR-59-targeting potential genes was assessed by qPCR (B).",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "HGAFDFN003 cells were transfected with anti-miR-ctrl or anti-miR-59 for 5 days, The protein expression of HMGA1 and HMGA2 was detected by western blot (C).",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "D, After transfection with anti-miR-ctrl or anti-miR-59 in progerin-expressing CRL-1474 cells, the protein expression (D) of HMGAs were detected.",
    "ncbi_link": "miR-59: 
progerin: "
  },
  {
    "caption": "After transfection with anti-miR-ctrl or anti-miR-59 in progerin-expressing CRL-1474 cells, mRNA level (E) of HMGAs were detected.",
    "ncbi_link": "miR-59: 
progerin: "
  },
  {
    "caption": "Western blot analysis the expression of HMGAs (F) in miR-ctrl or miR-59 mimics-transfected CRL-1474 cells.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "qPCR analysis the mRNA levels (G) in miR-ctrl or miR-59 mimics-transfected CRL-1474 cells.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "Transfected anti-miR-ctrl or anti-miR-59 in 88-year-old cells, the level of HMGAs was detected by Western blot (L)",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "Transfected anti-miR-ctrl or anti-miR-59 in 88-year-old cells, the level of HMGAs was detected by qPCR (M).",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "N, O The binding sites of miR-59 on HMGAs 3′ UTR were analyzed by TargetScan and miRanda. Luciferase experiments with the wild-type and the mutated 3′ UTR of HMGA1 (N) / HMGA2 (O).",
    "ncbi_link": "Luciferase: 
miR-59: 
HMGA1: 3159
HMGA2: 8091"
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), the level of cyclin A2, lamin B1 was detected by western blot (A).",
    "ncbi_link": "Flag: 
HMGA1: 
HMGA2: "
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), SA-β-gal staining were performed, the percentage of SA-β-gal positive cells was calculated.",
    "ncbi_link": "Flag: 
HMGA1: 
HMGA2: "
  },
  {
    "caption": "In Flag-HMGA1 or Flag-HMGA2 infected CRL-1474 and HGPS cells (HGAFDFN003), Expression of Ki67 was analyzed by immunofluorescence. Scale bars: 50 μm (C).",
    "ncbi_link": "Flag: 
HMGA1: 
HMGA2: "
  },
  {
    "caption": "Progerin-expressing CRL-1474 cells were transfected with His-control or His-HMGA1. SA-β-gal staining was performed. The percentage of SA-β-gal positive cells was calculated. Scale bars: 100 μm (D).",
    "ncbi_link": "His: 
HMGA1: 
Progerin: "
  },
  {
    "caption": "Progerin-expressing CRL-1474 cells were transfected with His-control or His-HMGA1. The level of cyclin A2, lamin B1 was detected by western blot (E).",
    "ncbi_link": "His: 
HMGA1: 
Progerin: "
  },
  {
    "caption": "Infection with control shRNA (shCtrl) or HMGA1/HMGA2 shRNA (shHMGA1 and shHMGA2) in anti-miR-59-transfected HGPS cells (HGAFDFN003), cells were subjected to SA-β-gal staining. Scale bars: 100 μm (F). Cells were subjected to immunofluorescence using anti-Ki67(red) antibody (left). The percentage of the Ki67 positive cells was calculated. Scale bars: 50 μm (G).",
    "ncbi_link": "miR-59: 
HMGA1: 3159
HMGA2: 8091"
  },
  {
    "caption": "Infection with control shRNA (shCtrl) or HMGA1/HMGA2 shRNA (shHMGA1 and shHMGA2) in anti-miR-59-transfected HGPS cells (HGAFDFN003) The level of cyclin A2, lamin B1, HMGA1 and HMGA2 was detected by western blot (H).",
    "ncbi_link": "miR-59: 
HMGA1: 3159
HMGA2: 8091"
  },
  {
    "caption": "HEK293T cells were transfected with Flag-HMGA1 (E) HMGA1 was IP with anti-Flag antibody and anti-CDK7 antibody.",
    "ncbi_link": "Flag: 
HMGA1: "
  },
  {
    "caption": "HEK293T cells were transfected with CDK7 (F). HMGA1 or CDK7 was IP with anti-Flag antibody and anti-CDK7 antibody.",
    "ncbi_link": "CDK7: "
  },
  {
    "caption": "G HEK293T cell lysates were incubated with GST or GST-HMGA1 sepharose beads. Pulled-down protein complexes were analyzed.",
    "ncbi_link": "GST: "
  },
  {
    "caption": "I HEK293T cells were transfected with Flag-HMGA1 deletion mutants. IP of Flag was performed. Pulled-down protein complexes were analyzed.",
    "ncbi_link": "Flag: 
HMGA1: "
  },
  {
    "caption": "J HEK293T cell lysates were incubated with GST or GST-HMGA1 deletion mutants sepharose beads. Recombinant proteins from pull-down assays visualized by silver staining and western blot.",
    "ncbi_link": "GST: 
HMGA1: "
  },
  {
    "caption": "K, L Progerin-expressing H1299 cells were transfected with His-control or His-HMGA1. Immunoprecipitation of RNA Pol II (K) or CDK7 (L) with anti-RNAPII antibody or anti-CDK7 antibody was performed, respectively. Pulled-down protein complexes were analyzed.",
    "ncbi_link": "His: 
HMGA1: 
Progerin: "
  },
  {
    "caption": "O Progerin-expressing CRL-1474 cells were transfected with His-control or His-HMGA1. Indicated proteins and modifications were detected by western blot.",
    "ncbi_link": "His: 
HMGA1: 
Progerin: "
  },
  {
    "caption": "P Infection with siCtrl or siCDK7 in Flag-HMGA1-transfected HGPS cells (HGAFDFN003), cyclin A1, RNAPII, the RNAPII Ser2P and RNAPII Ser5P was detected.",
    "ncbi_link": "Flag: 
HMGA1: 
CDK7: 1022"
  },
  {
    "caption": "Q Infection with control shRNA (shCtrl) or HMGA1 shRNA (shHMGA1) in anti-miR-59-transfected HGAFDFN003 cells. Indicated proteins and modifications were detected by western blot.",
    "ncbi_link": "miR-59: 
HMGA1: 3159"
  },
  {
    "caption": "F HGAFDFN003 cells were infected with His-HMGA1 and the mRNA level of cell cycle genes was assessed by qPCR.",
    "ncbi_link": "His: 
HMGA1: "
  },
  {
    "caption": "G Infection with control shRNA (shCtrl) or HMGA1 shRNA (shHMGA1) in anti-miR-59-transfected HGAFDFN003 cells. The mRNA level of cell cycle genes was assessed by qPCR.",
    "ncbi_link": "miR-59: 
HMGA1: 3159"
  },
  {
    "caption": "A miR-59 was detected in heart, liver, lung, kidney, skin, muscle, and brain of LmnaG609G/G609G mice by qPCR at 12 weeks of life (n=5 for each group).",
    "ncbi_link": "miR-59: 
Lmna: 16905"
  },
  {
    "caption": "B, C The mRNA level of Hmga1 (B) and Hmga2 (C) was detected in heart, liver, lung, kidney, skin, muscle and brain of LmnaG609G/G609G mice by qPCR at 12 weeks of life (n=5 for each group).",
    "ncbi_link": "Hmga1: 15361
Hmga2: 15364
Lmna: 16905"
  },
  {
    "caption": "D Transfected anti-miR-Ctrl or anti-miR-59 in progerin-expressing NIH3T3 cells. Western blot analysis of HMGAs.",
    "ncbi_link": "miR-59: 
progerin: "
  },
  {
    "caption": "G, H Luciferase experiments with the wild-type and the mutated 3′ UTR of Hmga1 and Hmga2.",
    "ncbi_link": "Hmga1: 15361
Hmga2: 15364"
  },
  {
    "caption": "A The in vivo therapy scheme. Eight-day-old mice were injected intraperitoneally with AAV9-mCherry-anti-miR-59 (5x1011 viral particles). The mCherry signals were detected 30 days post-injection (DPI) in LmnaG609G/G609G mice versus PBS-injected control (dorsal).",
    "ncbi_link": "mCherry: 
miR-59: 
Lmna: 16905"
  },
  {
    "caption": "B Expression of the mCherry reporter in different organs at 30DPI in LmnaG609G/G609G mice versus PBS-injected control. Hrt, Mscl, Ver, Kid, Liv: heart, Muscle, vertebrae, kidney, liver. AAV9-mCherry-anti-miR-59 was injected into 8-day-old mice and detected at different points.",
    "ncbi_link": "mCherry: 
miR-59: 
Lmna: 16905"
  },
  {
    "caption": "C, D The gross morphology of the wild-type and LmnaG609G/G609G mice which injected with anti-ctrl or anti-miR-59 for 14 weeks.",
    "ncbi_link": "miR-59: 
Lmna: 16905"
  },
  {
    "caption": "E Progression of body weight of male mice transduced with anti-Ctrl versus anti-miR-59 was detected from 4 weeks of life. The sample size (n) indicates the initial number of mice at week 4, initial n=10 WT; n=9 anti-Ctrl-transduced mice; n=7 anti-miR-59-transduced mice. Shown are mean values ± standard deviations, two-sided t-test was used when comparing anti-Ctrl-transduced mice and anti-miR-59-transduced mice from week 6-16.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "F Body weight comparison at 7- and 11-week-old male mice (n=9 anti-Ctrl-transduced mice; n=7 anti-miR-59-transduced mice). Data are presented as the mean ± SD (*P<0.05, **P<0.01). P-values were calculated by unpaired Student's t-test.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "G Progression of body weight of female mice transduced with anti-Ctrl versus anti-miR-59 was detected from four weeks of life. The sample size (n) indicates the initial number of mice at week 4, initial n=5 WT; n=6 anti-Ctrl-transduced mice; n=6 anti-miR-59-transduced mice. Shown are mean values ± standard deviations, two-sided t-test was used when comparing anti-Ctrl-transduced mice and anti-miR-59-transduced mice from week 6-16.",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "I Kaplan-Meier survival plot of the wild-type and LmnaG609G/G609G mice which injected with anti-Ctrl or anti-miR-59 (n=12 WT; n=13 anti-Ctrl-transduced mice; n=13 anti-miR-59-transduced mice, two-sided log-rank test).",
    "ncbi_link": "miR-59: 
Lmna: 16905"
  },
  {
    "caption": "A Running ability of male mice transduced with anti-Ctrl versus anti-miR-59 at 12 weeks of life (n=5 for each group).",
    "ncbi_link": "miR-59: "
  },
  {
    "caption": "E The level of miR-59 was detected in heart, liver, lung, kidney, skin, and muscle of LmnaG609G/G609G mice (n=5 for each group). F, G The mRNA level of Hmga1 (F) and Hmga2 (G) was detected in heart, liver, lung, kidney, skin, and muscle of LmnaG609G/G609G mice (n=5 for each group). H Hmgas immunohistochemistry in skin of WT mice and LmnaG609G/G609G mice. Scale bars, 50 μm. D",
    "ncbi_link": "miR-59: 
Hmga1: 15361
Hmga2: 15364
Lmna: 16905"
  },
  {
    "caption": "HEK 293T cells were transfected with doxycycline-inducible DmrB-caspase-8 and the indicated GSDMD constructs. Cells were stimulated with doxycycline (10 μg/ml) for 18 h to induce DmrB-caspase-8 expression and exposed to B/B homodimerizer (12.5 nM) for another 2 h to activate caspase-8. Mixed supernatant and extracts were analysed by immunoblot.",
    "ncbi_link": "caspase-8: 12370
GSDMD: 79792"
  },
  {
    "caption": "Immortalized Gsdmd-/- BDMDs expressing GSDMDWT and GSDMDD88A were costimulated with TNF (100 ng/ml) and SM for 6 h and LDH release was quantified.",
    "ncbi_link": "Gsdmd: 79792
GSDMD: 79792"
  },
  {
    "caption": "Immortalized Gsdmd-/- BDMDs expressing GSDMDWT and GSDMDD88A were primed for 3 h with ultrapure E. coli K12 LPS (100 ng/ml) and stimulated with LCL161 (1 μM) for 24 h and LDH release was quantified.",
    "ncbi_link": "GSDMD: 79792
Gsdmd: 79792"
  },
  {
    "caption": "D. Northern blot analysis of V. cholerae wild-type strain examined for the expression of VcdRP monitored over bacterial growth in the indicated media. The solid triangle represents the band corresponding to the full length primary vcdRP transcript, whereas the open triangles correspond to the different processed isoforms. Probing with 5S rRNA confirmed equal loading.",
    "ncbi_link": "vcdRP: 
5S rRNA: 
VcdRP: "
  },
  {
    "caption": "A. Northern blot analysis of the expression of VcdRP and Spot42 sRNA monitored at low cell density (OD600 of 0.1) and high cell density (OD600 of 2.0), in the absence (-) or presence (+) of cAMP (5mM f.c.) supplemented externally in LB medium. The solid triangle indicates the band corresponding to the full-length primary transcript. Probing with 5S rRNA confirmed equal loading.",
    "ncbi_link": "5S rRNA: 
Spot42: 
VcdRP: "
  },
  {
    "caption": "B. Western blot analysis (top) of CTX levels detected in secreted protein fractions of V. cholerae ΔhapR cells grown under AKI conditions and carrying the indicated plasmids. Coomassie-stained SDS gel (bottom) confirmed equal loading of the protein fractions. The normalized band intensities are indicated for each expression plasmid relative to pCtrl, which was set to 100%.",
    "ncbi_link": "hapR: "
  },
  {
    "caption": "I-L. Relative fluorescence intensities (y-axis) of E. coli strains harboring the gene-specific translational reporters as in (A-D) or the corresponding M2* variant for each gene, combined with an empty control plasmid or vcdRP expression plasmids (pVcdRP and pVcdRP M2) measured using plate reader (I-K) or by Western blot analysis (L). The fluorescence of pCtrl (for each reporter fusion) was set to 1.",
    "ncbi_link": "vcdRP: 
VcdRP: "
  },
  {
    "caption": "A. Immunoprecipitation of chromosomally tagged GltA::HA combined with either an empty vector control (pCtrl) or SPA-tagged vcdP over-expression plasmid, grown in LB medium to exponential phase (OD600 of 0.5). The SPA epitope contains the 3×FLAG and the calmodulin binding peptide sequences separated by a TEV protease cleavage site (Zeghouf et al, 2004). Therefore, protein samples corresponding to the total input and cell lysates before and after subjecting to immunoprecipitation with anti-Flag antibody were loaded on a SDS-PAGE gel. Western blotting with anti-HA and anti-Flag antibodies confirmed the interaction of GltA with VcdP in vivo. RNAP served as loading control. The solid triangles indicate the corresponding protein sizes.",
    "ncbi_link": "vcdP: 
SPA: "
  },
  {
    "caption": "B. Citrate synthase enzyme activity measurements performed on cellular lysates. An empty vector control (pCtrl) or vcdP expression plasmids (pVcdP and pVcdP*) were conjugated into V. cholerae wild-type, ΔvcdRP, ΔgltA or F383A GltA backgrounds. Cells were grown in LB medium to stationary phase and subsequently lysed. The protein concentrations of these cellular extracts were measured, and served as input for the assay. The resulting colorimetric product at 412nm was proportional to the enzymatic activity of citrate synthase present. The enzyme kinetics were assayed at 15 second intervals for at least 30 minutes and the activity per milligram of lysate was determined from the initial velocities.",
    "ncbi_link": "vcdP: 
VcdP: "
  },
  {
    "caption": "Co-immunoprecipitation  assays in HEK293T  cells after co-transfection with Flag-TRIM27  and the indicated combinations of empty HA-vector, HA-tagged FIP200, ULK1, or ATG13  before immunoprecipitation  with anti-HA  antibodies. Immunoprecipitates  (top panel) and input samples (bottom panel) were then subjected to Western blotting against anti-HA  or Flag. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
HA: 
ATG13: 9776
FIP200: 9821
TRIM27: 5987
ULK1: 22241"
  },
  {
    "caption": "C-F. WT (C), FIP200  knockout (KO) (D), ULK1/2 knockout (E) MEF  cells or ATG13  knockout 4T1  cells (F) were subjected to starvation conditions before immunoprecipitation  against control Immunoglobulin G (IgG) or anti-TRIM27  before blotting  against the indicated endogenous forms of TRIM27, FIP200, ULK1, ATG13, and USP7. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "ATG13: 51897
FIP200: 12421
ULK1: 22241"
  },
  {
    "caption": "G. Co-immunoprecipitation assays in HEK293T  cells after co-transfection with Flag-TRIM27  and either full length ULK  (HA-ULK1  1-1051) or the indicated various truncated forms of ULK1  designated HA-ULK1  1-828, HA-ULK1  1-600, and HA-ULK1  1-500; AA,  amino acids. Data information: , the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
HA: 
TRIM27: 5987
ULK: 22241
ULK1: 22241"
  },
  {
    "caption": "H. Co-immunoprecipitation assays in HeLa  cells stably expressing HA-ULK1   and immunoprecipitation  against IgG or HA  followed by Western blotting as indicated. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "HA: 
ULK1: 22241"
  },
  {
    "caption": "HeLa cells stably expressing Flag-TRIM27  were starved as indicated or starved  for 2h before replenishing  with complete medium. Anti-Flag immunoprecipitates  (top panel) and input samples (bottom panel) were then subjected to blotting  against Flag and ULK1. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "Ubiquitination  assays in HEK293T  cells after co-transfection with HA-ULK1  and His-Ub  along with Flag-TRIM27 (A) Samples recovered with  Ni-NTA  (top panel) and input samples (bottom panel) were then subjected to blotting  against anti-HA, Flag  or His  as indicated. Data information: , the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
HA: 
His: 
TRIM27: 5987
Ub: 7314
ULK1: 22241"
  },
  {
    "caption": "Ubiquitination  assays in HEK293T  cells after knockdown of TRIM27  using independent shRNAs (shTRIM27-1 and -2) (B). Samples recovered with  Ni-NTA  (top panel) and input samples (bottom panel) were then subjected to blotting  against anti-HA  or His  as indicated. Data information: , the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "C. In vitro ubiquitination  assays performed with the indicated combinations of recombinant GST, GST-TRIM27, affinity-purified HA-ULK1  and His-Ub  in the presence or absence of E1, E2, and ATP. The reactions were analyzed with anti-Ub, anti-HA, or anti-GST. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Ub: 7314"
  },
  {
    "caption": "Western blot  analysis of ULK1  levels in HeLa  cells stably expressing control or TRIM27  shRNAs (D) Data information: , the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "Western blot analysis of HEK293T  cells transfected with empty Flag  vector (-) or Flag-TRIM27  after treatment with or without 10 μM MG132  for 4 hours (E). Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "HA-ULK1  levels in 50 μg/mL cycloheximide  (CHX)-treated HEK293T  cells with or without co-expression of Flag-TRIM27 (G, H) Western blots  against HA-ULK1  and actin  control (G, were subjected to densitometric  quantitation (H, Data information: the experiments were performed at least three times independently with similar results. All the statistical data are presented as mean ± s.d. of three independent experiments. Statistical analysis was performed using two-tailed unpaired Student's t-tests (H , **P < 0.01.",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "endogenous ULK1  levels (I, J) in 50 μg/mL cycloheximide  (CHX)-treated HEK293T  cells or without TRIM27  RNAi (I, J). and actin  control I) were subjected to densitometric  quantitation J). Data information: the experiments were performed at least three times independently with similar results. All the statistical data are presented as mean ± s.d. of three independent experiments. Statistical analysis was performed using two-tailed unpaired Student's t-tests J), **P < 0.01.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "Ubiquitination  assays were performed in HEK293T  cells after co-transfection with full length HA-ULK1  or the indicated truncated constructs (K) in the presence or absence of Flag-TRIM27. Data information: , the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
HA: 
TRIM27: 5987
ULK1: 22241"
  },
  {
    "caption": "Ubiquitination  assays were performed in HEK293T  cells after co-transfection with double (K568/K571R) or single (K568R, K571R) lysine  substitution mutants (L) in the presence or absence of Flag-TRIM27. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "M. Ubiquitination  of HA-ULK1  in cells co-expressing Flag-TRIM27  with either His-Ub  WT, His-Ub  K48, or His-Ub  K63, respectively. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "Flag: 
His: 
TRIM27: 5987
Ub: 7314"
  },
  {
    "caption": "O. ULK1/2 knockout MEFs  stably expressing the indicated HA-ULK1  constructs were subjected to  Western blot  analysis against HA  or actin  before (0h) and after treatment with CHX  for 12 hours. Data information: the experiments were performed at least three times independently with similar results.",
    "ncbi_link": "HA: 
ULK1: 22241"
  },
  {
    "caption": "A. Western blot  analysis of autophagy  marker proteins (p62  and Ser318 phosphorylated ATG13) in WT HeLa  cells and two independent TRIM27  KO clones. ULK1  and TRIM27  levels were measured, along with actin  as a loading control.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "B. TRIM27  KO HeLa  cells were reconstituted with Flag-TRIM27  and Western blotting was performed as per (A).",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "C. LC3  conversion was measured by  Western blot in WT or TRIM27  KO HeLa  cells with or without pretreatment with 200 nM bafilomycin A1 (BAF A1).",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "D. Western blot  analysis of indicated proteins in MEFs  generated from Trim27  +/+ or Trim27 -/- mice.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "E-H. Immunofluorescence  analysis of endogenous LC3  in MEFs  generated from Trim27+/+ or Trim27-/- mice  cultured in fed  (E) or starved  conditions (G). Quantification of LC3B  puncta Fed  conditions (F), starved  conditions (H) (n = 50 cells per condition). Data are mean ± s.d. in F and H. Scale bar, 10 μm. Data information: (F, H, Statistical analysis was performed using two-tailed unpaired Student's t-tests, *P< 0.05,***P<0.001.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "I-J. Western blot analysis of autophagy  markers in the kidneys   of three-month-old Trim27  +/+ and Trim27-/- mice. Each lane represents a different mouse  (I). Quantification of p62,  LC3-II/LC3-I  ratio, and LC3-II/actin  ratio in I (J). Data are mean ± s.e.m. for three mice  per genotype. Data information: J, Statistical analysis was performed using two-tailed unpaired Student's t-tests, *P< 0.05,***P<0.001.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "A. Ubiquitination  analysis of HA-ULK1 in HeLa derivatives co-expressing His-Ub  with or without TRIM27  knockout, the cells were treated with starvation  for the indicated time.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "B. Western blot  analysis of ULK1 levels in HeLa  cells with or without TRIM27  knockout. The cells were treated with starvation  for the indicated time. The lysates were analyzed using anti-ULK1, anti-TRIM27, or anti-Actin.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "C. HA-ULK1, HA-ULK1  K568/K571R were stably expressed in ULK1  knockout HeLa  cells, the cells were treated with starvation, the lysates were analyzed by  western blot using anti-HA, or anti-Actin.",
    "ncbi_link": "HA: 
ULK1: 22241
ULK1: 8408"
  },
  {
    "caption": "E. Co-immunoprecipitation of Flag-TRIM27  with HA-ULK1  in HEK293T  cells with or without STK38L  knockdown, the cells were treated with starvation. Flag-TRIM27  was immunoprecipitated  using anti-Flag, the bound HA-ULK1  was detected using anti-HA.",
    "ncbi_link": "STK38L: 23012"
  },
  {
    "caption": "G. Co-immunoprecipitation  of Flag-STK38L  with ULK1, or TRIM27  in HEK293T  cells with or without starvation  treatment. Flag-STK38L   was immunoprecipitated  using anti-Flag, the immunoprecipitates  and lysates were analyzed with anti-ULK1, anti-TRIM27.",
    "ncbi_link": "Flag: 
STK38L: 23012"
  },
  {
    "caption": "H. Co-immunoprecipitation of endogenous TRIM27  with endogenous ULK1  in HeLa  cells with or without STK38L  knockout. The cells were treated with starvation before lysis.",
    "ncbi_link": "STK38L: 23012"
  },
  {
    "caption": "I. Western blot analysis of ULK1  levels in starved HeLa  cells expressing either Myc-STK38L, or Flag-TRIM27, or both. The lysates were analyzed using anti-ULK1, anti-Flag, anti-Myc, or anti-actin.",
    "ncbi_link": "Flag: 
Myc: 
STK38L: 23012
TRIM27: 5987"
  },
  {
    "caption": "J. Ubiquitination  analysis of HA-ULK1  in HEK293T  cells co-expressing Flag-TRIM27  and His-Ub, or together with Myc-STK38L.",
    "ncbi_link": "Flag: 
His: 
Myc: 
STK38L: 23012
TRIM27: 5987
Ub: 7314"
  },
  {
    "caption": "K. Western blot  analysis of ULK1  levels in HeLa  cells with or without STK38L  knockout, the cells were treated with starvation  for the indicated time.",
    "ncbi_link": "STK38L: 23012"
  },
  {
    "caption": "L.  Western blot analysis of p62  or LC3  levels in HeLa  cells with or without STK38L  knockout, the cells were treated with starvation  for the indicated time. Bafilomycin A1 (BAF A1) was used to inhibit the fusion between autophagosomes  and lysosomes.",
    "ncbi_link": "STK38L: 23012"
  },
  {
    "caption": "A. Western blot  analysis of ULK1  levels in HeLa cells stably expressing Flag-TRIM27, the cells were transfected with either Myc-vector, Myc-STK38L, or Myc-STK38L-K119A. Then the cells were treated with starvation before lysis.",
    "ncbi_link": "Flag: 
Myc: 
STK38L: 23012
TRIM27: 5987"
  },
  {
    "caption": "B. Phosphorylation  of HA-ULK1  in HeLa STK38L  knockout cells with or without expression of Flag-STK38L. HA-ULK1  was immunoprecipitated  and then analyzed by western blot using anti-phosphoserine  or anti-phosphothreonine, and the cell lysates were analyzed using anti-HA  and anti-Myc.",
    "ncbi_link": "Flag: 
STK38L: 23012"
  },
  {
    "caption": "C. Co-immunoprecipitation of Flag-TRIM27  with HA-ULK1  or HA-ULK1-S495A in HEK293T  cells. HA-ULK1  or HA-ULK1 S495A was immunoprecipitated  using anti-HA, the immunoprecipitates  and lysates were analyzed with anti-HA  or anti-Flag.",
    "ncbi_link": "HA: 
ULK1: 22241"
  },
  {
    "caption": "D. Ubiquitination  analysis of HA-ULK1  WT or HA-ULK1  S495A in HEK293T cells co-expressing Flag-TRIM27  and His-Ub.",
    "ncbi_link": "Flag: 
HA: 
His: 
TRIM27: 5987
Ub: 7314
ULK1: 22241"
  },
  {
    "caption": "E. Phosphorylation  of HA-ULK1  in HEK293T  cells co-expressing Myc-STK38L  with or without CIP  treatment. HA-ULK1  was immunoprecipitated  with anti-HA  and analyzed by western blot using a specific antibody against p-ULK1-S495 (Ser495).",
    "ncbi_link": "Myc: 
STK38L: 23012"
  },
  {
    "caption": "F. Phosphorylation  of HA-ULK1 or HA-ULK1  S495A in HEK293T  cells co-expressing Myc-STK38L. HA-ULK1  or HA-ULK1  S495A was immunoprecipitated  with anti-HA  and analyzed by western blot using a specific antibody against p-ULK1-S495 (Ser495).",
    "ncbi_link": "HA: 
STK38L: 23012
ULK1: 22241"
  },
  {
    "caption": "H. Ubiquitination  analysis of Myc-STK38L  in HEK293T  cells co-expressing Flag-TRIM27  and His-Ub.",
    "ncbi_link": "Flag: 
TRIM27: 5987"
  },
  {
    "caption": "I. Ubiquitination  analysis of Flag-STK38L  in HEK293T  cells co-expressing His-Ub  with or without TRIM27  knockdown, cells were cultured in fed  or starved  conditions as indicated.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "J. Ubiquitination  analysis of Flag-STK38L  in HEK293T  cells co-expressing Myc-TRIM27  with either His-Ub  (wild-type) or His-Ub  K6R.",
    "ncbi_link": "Myc: 
TRIM27: 5987
Ub: 7314"
  },
  {
    "caption": "K. Ubiquitination  analysis of Myc-STK38L  WT, Myc-STK38L-K432R+K434R or Myc-STK38L-K181R+K215R+K224R+K432R+K434R (Myc-STK38L-5KR) mutant in HEK293T  cells co-expressing HA-TRIM27  and His-Ub.",
    "ncbi_link": "HA: 
Myc: 
STK38L: 23012
TRIM27: 5987"
  },
  {
    "caption": "L. Ubiquitination  analysis of Myc-STK38L  K1-38R mutant (All lysines  were mutated to arginines), or Myc-STK38L-R181/215/224/432/434K (All lysines were mutated to arginines except the indicated five lysine  residues) mutant in HEK293T  cells co-expressing HA-TRIM27  and His-Ub.",
    "ncbi_link": "HA: 
Myc: 
STK38L: 23012
TRIM27: 5987"
  },
  {
    "caption": "M. Phosphorylation  of HA-ULK1  S495(Ser495) in HEK293T  cells co-expressing Myc-STK38L  WT, or Myc-STK38L-5KR mutant in K. The cells were cultured in fed  or starved  conditions as indicated and HA-ULK1  was immunoprecipitated  using anti-HA, the immunoprecipitates  and lysates were analyzed with a specific antibody against p-ULK1-S495 (Ser495), anti-Myc, anti-HA, or anti-actin.",
    "ncbi_link": "Myc: 
STK38L: 23012"
  },
  {
    "caption": "N. Phosphorylation  of HA-ULK1  in HeLa  cells with or without TRIM27-knockout, cells were cultured in fed  or starved  conditions as indicated, HA-ULK1  was immunoprecipitated  using anti-HA, the immunoprecipitates  and lysates were analyzed with a specific antibody against p-ULK1-S495 (Ser495), anti-HA, or anti-actin.",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "A. Comparison of the relative mRNA levels of TRIM27  in normal breast  tissues (Normal, n=113) and indicated breast   tumors (Basal，n=143；Her2，n=67；LumA，n=427；LumB，n=190) in the TCGA database. The number of biological replicates are shown as indicated. P < 0.0001 (one-way ANOVA).",
    "ncbi_link": "TRIM27: 5987"
  },
  {
    "caption": "F. Representative tumors  in MMTV-PyMT mice  of the indicated Trim27  genotypes. Scale bar, 5mm.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "G.  Western blot  analysis of indicated proteins in Trim27-/- PyMT or Trim27+/- PyMT mice  in primary breast  tumors. Actin was used as a loading control.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "H. Kaplan-Meier tumor-free survival curves of Trim27+/- PyMT  (median = 75 d, number = 20), or Trim27  -/- PyMT mice  (median = 95 d, number = 16). P < 0.0001 (Mantel-Cox test).",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "Pulmonary  surface nodules  in Trim27+/- PyMT mice  and Trim27-/- PyMT mice (I Scale bar, 1mm.",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "Pulmonary surface nodules   and hematoxylin  and eosin  (H&E) staining  in Trim27+/- PyMT mice  and Trim27-/- PyMT mice  J). Scale bar, 1mm. (K). Bar chart showing quantification for the number of metastatic nodules  per lung lope (Trim27+/-, n=6 mice; Trim27-/- n=6 mice), when compared at the same final timepoint. Each symbol represents a mouse; Data are presented as mean ± s.d. from three independent experiments; ***P<0.001 (unpaired student's t-test).",
    "ncbi_link": "Trim27: 19720"
  },
  {
    "caption": "The number of neoblasts did not change significantly following inhibition of the MTC-gene kiaa1429. Shown is FISH of smedwi-1 (A) in control and kiaa1429 (RNAi) animals (left). smedwi-1+ cells were counted following FISH and showed no significant difference in expression (right; bar represents average normalized cell count; Materials and Methods). Scale = 100 µm.",
    "ncbi_link": "kiaa1429: 
smedwi-1: "
  },
  {
    "caption": "The number of neoblasts did not change significantly following inhibition of the MTC-gene kiaa1429. Shown is FISH of h2b (B) in control and kiaa1429 (RNAi) animals (left). h2b+ cells were counted following FISH and showed no significant difference in expression (right; bar represents average normalized cell count; Materials and Methods). Scale = 100 µm.",
    "ncbi_link": "kiaa1429: 
h2b: "
  },
  {
    "caption": "(E) Representative FACS plots of cells isolated from control (top) and kiaa1429 (RNAi) animals (bottom) show an increase in cell abundance in the X2 (Fincher et al, 2018) gate (green; Materials and Methods). (F) Quantification of the cells in each FACS gate in control and kiaa1429 (RNAi) animals showed a six-fold increase in the abundance of cells in the X2 gate (Student's t-test *** - p < 0.005. FACS experiments were performed in biological triplicates. Boxes represent the IQR, whiskers represent the 1.5 x IQR, and central band represents the med",
    "ncbi_link": "kiaa1429: "
  },
  {
    "caption": "CAC was induced in control (n = 7) and ColVIcre-Kif3aflx/flx (n = 7) female mice according to the timeline shown in Figure 2A. (E) Representative images of hematoxylin and eosin staining of paraffin-embedded colon sections. Areas with high-grade dysplasia are delimited by black lines.",
    "ncbi_link": "ColVI: 12834///12833///245026///665033///68553///12835
cre: 2777477
Kif3a: 16568"
  },
  {
    "caption": "CAC was induced in control (n = 7) and ColVIcre-Kif3aflx/flx (n = 7) female mice according to the timeline shown in Figure 2A. (F,G,H,I) Box-and-whisker plots depicting area (F,G) and number (H,I) of low- and high-grade dysplasia per mouse.",
    "ncbi_link": "ColVI: 12833///12835///68553///665033///245026///12834
cre: 2777477
Kif3a: 16568"
  },
  {
    "caption": "(H) Elevated numbers of F4/80+ macrophages in colons of DSS-treated ColVIcre-Kif3aflx/flx mice. Representative images for F4/80 staining in areas with crypt loss are shown. At least 5 fields in the regions of crypt loss were analyzed from each colon of control (n=6) and ColVIcre-Kif3aflx/flx (n=6) mice. Mean cell numbers were scored as low (<500 cells/mm2) or high (>500 cells/mm2).",
    "ncbi_link": "ColVI: 12835///12834///12833///245026///665033///68553
cre: 2777477
Kif3a: 16568"
  },
  {
    "caption": "Elevated numbers of IL-6-expressing F4/80+ macrophages in ColVIcre-Kif3aflx/flx mice treated with DSS as described in Figure 4A. At least 5 fields in the regions of crypt loss were analyzed. Scale bar represent 100 µm. *p<0,05 was calculated by chi-squared test.",
    "ncbi_link": "ColVI: 12835///12834///12833///245026///665033///68553
cre: 2777477
Kif3a: 16568"
  },
  {
    "caption": "(E) Quantification of different phenotypes manifesting after RNA interference in comparison to control animals: MN2a axons projecting to the MHE muscle, representing the wild-type (wt) innervation pattern (magenta); MN2a axons projecting to muscles other than the MHE termed abnormal innervation (light grey); abnormal synaptic morphologies at MN2a derived axon terminals termed terminal defects (dark grey). Note, each genetic experiment was performed in parallel to an adequate control experiment using the same driver line crossed to a line that controls expression of either UAS-RFP or UAS-GFPRNAi. Each experiment was performed in triplicates, innervation rates were calculated from n=56 for elav>RFP, n=21 for elav>DfdRNAi, n=10 for elav>hthRNAi and n=7 for elav>mirrRNAi. In the case of Dfd knock-down, two different driver lines were used, the pan-neural elav-GAL4 and the motoneuron-specific OK6-GAL4 drivers, respectively. Both result in similar phenotypes, highlighting that the elav-GAL4 driven effects are specific to MNs. p-values between two genetic conditions were calculated by a two-sided Fisher test. ***: p < 0.005.",
    "ncbi_link": "GFP: 
RFP: 
Dfd: 40832
elav: 31000
GAL4: 855828
hth: 41273
mirr: 39441"
  },
  {
    "caption": "(B) Representative confocal images of stage 17 embryonic heads highlighting the expression of Dfd (purple), Myosin in muscles (blue) and FasII in axonal projections (green) in control (elav>RFP) animals and animals mis-expressing the Hox TFs Lab, Dfd and Scr by means of the elav-GAL4 driver. A zoom on the projections (FasII staining) of MN2a and MN3 to the MHE and MHD muscles of an early stage 17 Drosophila embryo are shown. Asterisks highlight the location of MN2a and MN3, respectively. MN2a is identified by the FasII expressing axonal projection emerging from a Dfd expressing MN, which normally innervates the Dfd expressing MHE muscle (as shown in the elav>RFP control), while MN3 is identified as the MN underneath MN2a, which normally innervates the MHD muscle (as shown in the elav>RFP control). The panel on the right side represents a schematic drawing of the confocal image shown on the left side, summarizing the innervation of the anterior muscles (LR, MHE, MHD) by projections emerging from MN2a (magenta) or MN3 (cyan) in control and mis-expression conditions.",
    "ncbi_link": "RFP: 
Dfd: 40832
elav: 31000
GAL4: 855828
Lab: 40817
Scr: 40833"
  },
  {
    "caption": "(A) Representative confocal images of stage 17 embryonic heads highlighting the expression of Myosin in muscles (blue) and FasII in axonal projections (green) in control (elav>RFP) animals and in animals with reduced neuronal DIPkappa (elav>DIPkappaRNAi) as well as in animals, which mis-express DIPgamma or dpr1 in neuronal cells (elav>DIPgamma, elav>dpr1). Single channels focusing on the projections (FasII staining) of MN2a and/or MN3 to the MHE, MHD or LR muscles of an early stage 17 Drosophila embryo are shown. Asterisks highlight the location of MN2a and MN3, respectively. MN2a is identified by the FasII expressing axonal projection emerging from a Dfd expressing MN, which normally innervates the Dfd expressing MHE muscle (as shown in the elav>RFP control), while MN3 is identified as the MN underneath MN2a, which normally innervates the MHD muscle (as shown in the elav>RFP control). The panel on the right represents a schematic drawing of the confocal images shown on the left side, summarizing the innervation of the anterior muscles (LR, MHE, MHD) by projections emerging from MN2a (magenta) or MN3 (cyan) in control and mis-expression conditions.",
    "ncbi_link": "RFP: 
DIPgamma: 43417
DIPkappa: 318958
dpr1: 2768858
elav: 31000"
  },
  {
    "caption": "(A) Representative confocal images of stage 17 embryonic heads highlighting the expression of Dfd (purple), Myosin in muscles (blue) and FasII in axonal projections (green) in control (elav>RFP) animals and in animals with reduced Dfd expression in neurons (elav>DfdRNAi) or in muscles (Mef2>DfdRNAi) or both in both tissues (elav;Mef2>DfdRNAi). The single channels for the projections (FasII staining) of MN2a and/or MN3 to the MHE, MHD or LR muscles of an early stage 17 Drosophila embryo are shown. Asterisks highlight the location of MN2a and MN3, respectively. MN2a is identified by the FasII expressing axonal projection emerging from a Dfd expressing MN, which normally innervates the Dfd expressing MHE muscle (as shown in the elav>RFP control), while MN3 is identified as the MN underneath MN2a, which normally innervates the MHD muscle (as shown in the elav>RFP control). The panel on the right side represents a schematic drawing of the confocal image shown on the left side, summarizing the innervation of the anterior muscles (LR, MHE, MHD) by projections emerging from MN2a (magenta) or MN3 (cyan) in control and perturbation conditions.",
    "ncbi_link": "RFP: 
Dfd: 40832
elav: 31000
Mef2: 36032"
  },
  {
    "caption": "Restoration of glucoseuptake or Akt signaling suppresses the thermogenic defect in AdRiKO mice. (A) HKII mRNA expression level in BAT of AdRiKO and control mice infected with either AAV9-HKII or AAV9-empty (n=8/group).",
    "ncbi_link": "HKII: 15277"
  },
  {
    "caption": "(B) Cold-induced 2-Deoxyglucose-6-phosphate (2DG6P) accumulation in BAT of AdRiKO and control mice infected with either AAV9-HKII or AAV9-empty housed at 4°C for 4h (n=8/group).",
    "ncbi_link": "HKII: 15277"
  },
  {
    "caption": "(C) Body temperature of AdRiKO and control mice infected with either AAV9-HKII or AAV9-empty housed at 22°C (n=8/group).",
    "ncbi_link": "HKII: 15277"
  },
  {
    "caption": "(D) Body temperature upon cold exposure of AdRiKO and control mice infected with either AAV9-HKII or AAV9-empty. The left panel represents body temperature after each hour of cold exposure while the right panel represents body temperature as a bar graph for the 3h cold exposure time point (n=8/group). a=significant difference between AdRiKO and control mice infected with AAV9-empty, b= significant difference between AdRiKO and control mice infected with AAV9-HKII, d= significant difference between AdRiKO mice infected with AAV9-empty and AAV9-HKII.",
    "ncbi_link": "HKII: 15277"
  },
  {
    "caption": "(E) Immunoblot analysis of BAT from AdRiKO and control mice infected with either AAV8-Akt2S474D or AAV8-empty (n=6/group, each lane represents a mix of 3 mice).",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "(F) Body temperature of AdRiKO and control mice infected with either AAV8-Akt2S474D or AAV8-empty housed at 22°C (n=11/group).",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "(G) Body temperature upon cold exposure of AdRiKO and control mice infected with either AAV8-Akt2S474D or AAV8-empty. The left panel represents body temperature after each hour of cold exposure while the right panel represents body temperature as a bar graph for the 3h cold exposure time point (n=11/group). a=significant difference between AdRiKO and control mice infected with AAV8-empty, b= significant difference between AdRiKO and control mice infected with AAV8-Akt2S474D, d= significant difference between AdRiKO mice infected with AAV8-empty and AAV8-Akt2S474D.",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "(H) Cold-induced 2-Deoxyglucose-6-phosphate (2DG6P) accumulation in BAT of AdRiKO and control mice infected with either AAV8-Akt2S474D or AAV8-empty housed at 4°C for 4h (n=7 (control AAV8-null), n=6 (AdRiKO AAV8-null), n=6 (control AAV8-AktS474D), n=6 (AdRiKO AAV8-AktS474D)). Data represent mean ± SEM. Statistically significant differences between AdRiKO and control mice were determined with unpaired Student's t-test and are indicated with asterisks (*=p<0.05; **=p<0.01, ***=p<0.001). Statistically significant differences between viruses were determined with unpaired Student's t-test and are indicated with a number sign (#=p<0.05; ##=p<0.01; ###=p<0.001). The exact p-value for each significant difference can be found in Appendix Table S2.",
    "ncbi_link": "Akt2: 11652"
  },
  {
    "caption": "A-F Shown are hypocotyl  lengths of cRL-grown 4-day-old seedlings of toc1  complemented with wild-type TOC1 (A), 5X (B), T135A (C), S175A (D) driven by TOC1 native promoter and wild-type TOC1 (E), 5X (F) driven by 35S  promoter at sequential fluent rates. Different letters indicate statistically significant differences between genotypes (p<0.01, one-way ANOVA followed by Tukey-Kramer HSD test), error bars indicate SEM. Data are representative of three biological trials with similar results.",
    "ncbi_link": "toc1: 836259
TOC1: 836259"
  },
  {
    "caption": "Hypocotyl lengths in SD condition of Col-0, toc1-101 and two independent native or 35S promoter lines of wild-type  TOC1 and each phosphosite mutants. The middle line of the box represents the median, the x in the box represents the mean. The bottom line and the top line of the box represent 1st and 3rd quartile, respectively. The whiskers extend from the ends of the box to the minimum value and maximum value. Data information: 18 to 27 seedlings  per line were entrained in 12h/12h light/dark cycles for 7 d and next transferred to constant red light at ZT2 for image acquisition with 2-h intervals for 1 week.",
    "ncbi_link": "toc1: 836259
TOC1: 836259"
  },
  {
    "caption": "C-E, Average CCA1:LUC bioluminescence traces of indicated plant lines. Data information: 18 to 27 seedlings per line were entrained in 12h/12h  light/dark cycles for 7 d and next transferred to constant red light at ZT2 for image acquisition with 2-h intervals for 1 week. White and gray regions indicate subjective  light and  dark  period. Data are representative of at least two independent trials with similar results. Different letters indicate statistically significant differences in period between genotypes (p<0.01, one-way ANOVA followed by Tukey-Kramer HSD test).",
    "ncbi_link": "LUC: 
CCA1: 819296"
  },
  {
    "caption": "A-C, PIL1, AT5G02580 and CDF5 expression pattern in 3-d-old SD-grown seedlings from indicated plant lines at night. Data is representative of 3 biological trials.",
    "ncbi_link": "CDF5: 843293
AT5G02580: 831095
PIL1: 819311"
  },
  {
    "caption": "C,  ChIP-qPCR assay of TOC1 binding  to promoter of pre-dawn-phased PIF3 target genes at ZT14 in  Col-0, native promoter TOC1 and 5X lines. D, ChIP-qPCR  assay of the chromatin residence of native promoter TOC1-GFP at target promoters in  toc1 vs. pif3/4/5 toc1 (pif345t1) mutant backgrounds. Data information: 3-d-old SD-grown  seedlings were harvested at ZT14, TOC1-GFP was  immunoprecipitated by α-GFP and magnetic protein G beads. Data from 3 independent trials were averaged, error bars indicate SEM. Asterisks indicates significant differences (** p<0.001, *** p<0.0001, Student's t test), n.s=not significant.",
    "ncbi_link": "PIF3: 837479
pif3: 837479
toc1: 836259
TOC1: 836259"
  },
  {
    "caption": "B, Measurement of TOC1-GFP protein turn-over in  TOC1, 5X, T135A, S175A native promoter lines by cycloheximide  (CHX) treatment. 10-d-old seedlings grown in 12h/12h light/dark cycles were subject to cycloheximide (CHX) or  ethanol (Mock) treatment for indicated  time length. Data from 3 independent trials were fitted to non-linear Weibull regression curves. Data information: TOC1  protein was detected by α-GFP, ADK  was used as loading control. TOC1/ADK ratio was calculated by the intensities of TOC1-GFP bands normalized by the intensities of ADK  bands using ImageJ.",
    "ncbi_link": "TOC1: 836259"
  },
  {
    "caption": "C, ChIP-qPCR assay of native promoter driven  TOC1-GFP and 5X-GFP's residence at target promoters in toc1 vs. nf-yc3/4/9 toc1 (c349t1) mutants. 3-d-old SD-grown  seedlings were harvested at ZT14, TOC1  and 5X were immunoprecipitated by α-GFP  and magnetic protein G beads. Data from 3 independent trials were averaged. Error bars indicate SEM, asterisks indicate significant differences (* p<0.05, *** p<0.0001, Student's t test), n.s= not significant.",
    "ncbi_link": "nf-yc3: 841922
toc1: 836259"
  },
  {
    "caption": "E, Expression of  PIL1, AT5G02580 and CDF5 in 3-d-old SD-grown  seedlings at ZT18. Data from 3 independent experiments were averaged. Error bars indicate SEM. Different letters denote statistically significant differences based on Wilcoxon test (p<0.05).",
    "ncbi_link": "CDF5: 843293
AT5G02580: 831095
PIL1: 819311"
  },
  {
    "caption": "A and B, ChIP-qPCR assay of  HDA15's (A) and NF-YC9's (B) residence at target promoters in presence or absence of TOC1  and PRR5. GFP-HDA15 and GFP-NF-YC9 driven by 35S promoter were transiently expressed in protoplasts isolated from  Col-0, toc1  single and prr5 toc1 double mutant grown in SD condition. Results were normalized by % input of PIL1 coding region (PIL1 CDS). Data from at least 3 independent experiments were averaged, error bars indicate SEM. Asterisks indicate significant differences (* p<0.05, ** p<0.001, *** p<0.0001, Student's t test).",
    "ncbi_link": "PIL1: 819311
PRR5: 832518
prr5: 832518
toc1: 836259
TOC1: 836259"
  },
  {
    "caption": "C and D, Dual  luciferase assay   of the repression activity of  GFP-TOC1 and  GFP-5X on promoter of AT5G02580 (C) and CDF5 (D) in protoplasts of toc1 and hda15toc1 (h15t1) mutants.  AT5G02580:LUC,  CDF5:LUC reporters and the effectors (empty GFP, GFP-TOC1, and GFP-5X) were co-transfected to toc1 and hda15 toc1 protoplasts with 35S:Renilla-LUC as internal control. Data are means ± SEM (n = 5 biological trials) relative to empty  GFP which is set as 1. Different letters indicate statistically significant differences (student's t test, p<0.05).",
    "ncbi_link": "GFP: 
LUC: 
CDF5: 843293
AT5G02580: 831095
hda15: 821382
TOC1: 836259
toc1: 836259"
  },
  {
    "caption": "C, ChIP-qPCR assay of native promoter TOC1-GFP and 5X-GFP binding to the target promoters at ZT14 in toc1  vs. prr5 toc1 (p5t1) mutant. 3-d-old SD-grown  seedlings were harvested at ZT14, TOC1  and 5X were  immunoprecipitated by α-GFP. Data from 3 independent trials were averaged, error bars indicate SEM. Asterisks indicate significant differences (Student's t test; * p<0.05), n.s= not significant.",
    "ncbi_link": "prr5: 832518
toc1: 836259"
  },
  {
    "caption": "D, Expression of PIL1, AT5G02580 and CDF5 in 3-d-old SD-grown  seedlings at ZT18. Data from 3 biological trials were averaged. Error bars indicate SEM. Different letters denote statistically significant differences based on Wilcoxon test (p<0.05).",
    "ncbi_link": "CDF5: 843293
AT5G02580: 831095
PIL1: 819311"
  },
  {
    "caption": "A Detection of the RBPJ/L3MBTL3 interaction using the yeast two-hybrid (Y2H) assay. In this Y2H experiment, RBPJ is fused to the GAL4 DNA-binding (DB) domain and L3MBTL3 is fused to the GAL4 activation domain (AD). The DB-RBPJ and AD-L3MBTL3 fusion proteins interact with each other, leading to the activation of the ADE2 and HIS3 reporter genes and allowing yeast cells to grow on selective media lacking adenine or histidine. The six Y2H controls were previously described (Dreze et al, 2010). The experiment was independently replicated thrice.",
    "ncbi_link": "ADE2: 854295
HIS3: 854377"
  },
  {
    "caption": "B/C NOTCH1 ICD outcompetes L3MBTL3 for binding to RBPJ in a dose-dependent manner. IPs were performed in CRISPR/Cas9-mediated L3MBTL3 knockout (KO) HEK293T cells. (B) SBP-FLAG-RBPJ and HA-L3MBTL3-Δ(SAM) in the presence of an increasing amount of HA-NOTCH1 ICD. The L3MBTL3-Δ(SAM) mutant construct was used instead of the L3MBTL3 WT construct in order to allow the analysis of both NOTCH1 ICD and L3MBTL3 proteins in the same Western blot. CRISPR/Cas9 sg-L3MBTL3-resistant plasmids were used to express HA-L3MBTL3-Δ(SAM). The experiment was independently replicated thrice. WB: Western blot; IP: immuno-precipitation.",
    "ncbi_link": "L3MBTL3: 84456"
  },
  {
    "caption": "B/C NOTCH1 ICD outcompetes L3MBTL3 for binding to RBPJ in a dose-dependent manner. IPs were performed in CRISPR/Cas9-mediated L3MBTL3 knockout (KO) HEK293T cells. (C) SBP-FLAG-RBPJ and HA-NOTCH1 ICD in the presence of an increasing amount of HA-L3MBTL3-Δ(SAM). The L3MBTL3-Δ(SAM) mutant construct was used instead of the L3MBTL3 WT construct in order to allow the analysis of both NOTCH1 ICD and L3MBTL3 proteins in the same Western blot. CRISPR/Cas9 sg-L3MBTL3-resistant plasmids were used to express HA-L3MBTL3-Δ(SAM). The experiment was independently replicated thrice. WB: Western blot; IP: immuno-precipitation.",
    "ncbi_link": "L3MBTL3: 84456"
  },
  {
    "caption": "A De-repression of Notch target genes upon RBPJ knockdown. Shown are means ±s.d. of quadruplicate experiments. [*] P<0.05, [**] P<0.01, NS: Not Significant; one-way ANOVA model on log-transformed data. Inset: Western blot analysis validates the shRNA-mediated depletion of RBPJ.",
    "ncbi_link": "RBPJ: 3516"
  },
  {
    "caption": "B De-repression of Notch target genes in L3MBTL3 KO U87-MG cells. Shown are means ±s.d. of quadruplicate experiments. [**] P<0.01, NS: Not Significant; two-sample T-test on log-transformed data. Inset: Western blot analysis validates the CRISPR/Cas9-mediated KO of L3MBTL3.",
    "ncbi_link": "L3MBTL3: 84456"
  },
  {
    "caption": "C RBPJ and L3MBTL3 co-localize at the proximal Notch-responsive elements of Notch target genes. Shown are means ±s.d. of triplicate ChIP experiments.In panels C, D and F: distance in base pairs (bp) relative to the transcriptional start site (TSS) is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "Chrom8: "
  },
  {
    "caption": "D L3MBTL3 occupancy at the proximal Notch-responsive elements of Notch target genes decreases upon RBPJ knockdown. Shown are means ±s.d. of triplicate ChIP experiments.In panels C, D and F: distance in base pairs (bp) relative to the transcriptional start site (TSS) is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "Chrom8: 
RBPJ: 3516"
  },
  {
    "caption": "E The repressive activity of L3MBTL3 at Notch target genes is RBPJ-dependent. Expression analysis of Notch target genes upon RBPJ knockdown and/or overexpression of L3MBTL3. Shown are means ±s.d. of triplicate experiments. P values were estimated via a one-way ANOVA model on log-transformed data where the difference of differences was tested, which is equivalent to testing the interaction in a two-way ANOVA model. Western blot analysis validates the overexpression of L3MBTL3 and the shRNA-mediated depletion of RBPJ (Appendix Fig S3E). Gene expression analyses of OCT4 was performed as control (Appendix Fig S3F).",
    "ncbi_link": "RBPJ: 3516"
  },
  {
    "caption": "F L3MBTL3 occupancy at the proximal Notch-responsive elements of Notch target genes is dependent on its RBPJ interaction domain. ChIP analyses of HA-L3MBTL3 WT and HA-L3MBTL3-Δ(1-64) occupancy at the proximal Notch-responsive elements of Notch target genes. Shown are means ±s.d. of duplicate experiments measured twice each.In panels C, D and F: distance in base pairs (bp) relative to the transcriptional start site (TSS) is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "Chrom8: "
  },
  {
    "caption": "G The L3MBTL3-(1-64) domain is required for the downregulation of HES1 and HEY2 in U87-MG cells. Expression analysis of Notch target genes upon overexpression of L3MBTL3 WT, L3MBTL3-Δ(1-64) or LacZ control (Control). Shown are means ±s.d. of triplicate experiments. [*] P<0.05, [**] P<0.01, NS: Not Significant; one-way ANOVA model on log-transformed data.",
    "ncbi_link": "HES1: 3280
HEY2: 23493"
  },
  {
    "caption": "A The RBPJ/KDM1A interaction is indirect and occurs via L3MBTL3. IP of HA-KDM1A in the presence of overexpressed V5-L3MBTL3 or V5-L3MBTL3-Δ(1-64) in L3MBTL3 KO U87-MG cells. CRISPR/Cas9 sg-L3MBTL3-resistant plasmids were used to overexpress the L3MBTL3 proteins. The experiment was independently replicated twice.",
    "ncbi_link": "L3MBTL3: 84456"
  },
  {
    "caption": "B KDM1A occupancy at the proximal Notch-responsive elements of Notch target genes is L3MBTL3-dependent. ChIP analysis of endogenous KDM1A in L3MBTL3 KO U87-MG cells. Shown are means ±s.d. of duplicate experiments measured twice each.Panels B, C and D: distance in bp relative to the TSS is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "Chrom8: 
L3MBTL3: 84456"
  },
  {
    "caption": "C KDM1A occupancy at the proximal Notch-responsive elements of Notch target genes is dependent on L3MBTL3 and both its RBPJ interaction and KDM1A interaction domains. ChIP analysis of endogenous KDM1A in L3MBTL3 KO U87-MG cells upon overexpression of L3MBTL3, L3MBTL3-Δ(1-64) or L3MBTL3-Δ(SAM). Control: empty vector. Shown are means ±s.d. of duplicate experiments measured twice each.Panels B, C and D: distance in bp relative to the TSS is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "Chrom8: 
L3MBTL3: 84456"
  },
  {
    "caption": "D L3MBTL3, but neither L3MBTL3-Δ(1-64) nor L3MBTL3-Δ(SAM), leads to decreasing H3K4me2 at the proximal Notch-responsive element of HES1. ChIP analysis of H3K4me2 at the proximal Notch-responsive element of HES1 upon overexpression of LacZ control (Control), L3MBTL3, L3MBTL3-Δ(1-64) or L3MBTL3-Δ(SAM) in L3MBTL3 KO U87-MG cells. Shown are means ±s.d. of duplicate experiments measured twice each. P values were estimated via a one-way ANOVA on log-transformed data.Panels B, C and D: distance in bp relative to the TSS is indicated below the gene names. Chrom8 was used as negative control (NEG).",
    "ncbi_link": "L3MBTL3: 
Chrom8: 
HES1: 3280
L3MBTL3: 84456"
  },
  {
    "caption": "E L3MBTL3, but neither L3MBTL3-Δ(1-64) nor L3MBTL3-Δ(SAM), represses HES1. Expression analysis of HES1 upon overexpression of LacZ control (Control), L3MBTL3, L3MBTL3-Δ(1-64) or L3MBTL3-Δ(SAM) mutants in L3MBTL3 KO U87-MG cells. Shown are means ±s.d. of triplicate experiments. P values were estimated via a one-way ANOVA on log-transformed data. NS: Not Significant. WB: Western blot; IP: immuno-precipitation. We note that in the context of this experiment, i.e., in the absence of endogenous L3MBTL3, the overexpression of L3MBTL3-Δ(1-64) does not result in the increased expression of HES1, contrasting with the result obtained in Fig 4G, i.e., in the presence of endogenous L3MBTL3. Indeed, as expected, the dominant negative effect of L3MBTL3-(1-64) on endogenous WT L3MBTL3's ability to repress the expression of Notch target genes can only be observed when WT L3MBTL3 is expressed.",
    "ncbi_link": "HES1: 3280
L3MBTL3: 84456"
  },
  {
    "caption": "C Snapshot showing the co-localization of dL(3)mbt and Su(H) at the dNotch (N) locus.",
    "ncbi_link": "dNotch: 31293"
  },
  {
    "caption": "F Functional interaction between lag-1/RBPJ and lin-61/L3MBTL3 during C. elegans vulva development. Proportion of animals (n ≥100) displaying a protruding vulva (Pvl) phenotype after RNAi treatment for two generations. Worms were grown at 25°C. Shown are means ±s.d of duplicate experiments. EV: Empty Vector control.",
    "ncbi_link": "lag-1: 177373
lin-61: 172467"
  },
  {
    "caption": "H Fluorescence microscopy of the SARS-CoV-2 GFP/ΔN or VSV-GFP  viruses in  Caco-2-N cells pretreated with VitC  (5 mM and 10 mM) for 24 hrs, and then infected with SARS-CoV-2 GFP/ΔN (MOI = 0.1) or VSV-GFP  (MOI = 0.1) viruses for 24 hrs. Data are representative of three biological replicates. Scale bar: 100 µm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A  RT-qPCR  analysis of Ace2  mRNA in 2fTGH  cells treated with VitC  (5 mM) as indicated. Data are shown as mean and s.d. of three biological replicates (n = 3). N.S, not significant (two-tailed unpaired Student's t-test).",
    "ncbi_link": "Ace2: 59272"
  },
  {
    "caption": "F IP-IB  analysis of ubiquitination  types of Myc-ACE2  in HEK293T  cells cotransfected with Myc-ACE2  and different types of HA-Ub, and then treated with VitC  (5 mM) for 12 hrs. The red dashed contour represents the group of K48-linked ubiquitination  we focused on studying here. Data are representative of three biological replicates.",
    "ncbi_link": "HA: 
Myc: 
Ub: 
ACE2: 59272"
  },
  {
    "caption": "G  Western blot  analysis of ACE2  in HEK293T  cells transfected with Flag-USP50  and then treated with CHX  (50 μM) as indicated. Data are representative of three biological replicates.",
    "ncbi_link": "Flag: 
USP50: 373509"
  },
  {
    "caption": "K Fluorescence microscopy  of the VSV  virus with a SARS-CoV-2-S gene and a GFP  gene (VSV-Spike) in Usp50+/+ and Usp50-/- HEK293T   cells pretreated with or without VitC  (5 mM) for 12 hrs, followed by infection  with the VSV-Spike  virus (MOI = 0.1) for 24 hrs. Scale bar: 100 µm. The average intensity each unit area was shown as mean and s.d. of three-unit areas (n = 3). N.S, not significant, ***p < 0.001 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "Usp50: 373509"
  },
  {
    "caption": "D IP-IB  analysis of ubiquitination  types of Myc-ACE2  in HEK293T  cells cotransfected with Myc-ACE2, Flag-USP50  and different types of HA-Ub. The red dashed contour represents the group of K48-linked ubiquitination  we focused on studying here. Data are representative of three biological replicates.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
Ub: 
ACE2: 59272
USP50: 373509"
  },
  {
    "caption": "E IP-IB  analysis of K48-Ub  of endogenous ACE2  in HEK293T  cells transfected with shCtrl (-) or shUSP50 (#1, #2). Data are representative of three biological replicates.",
    "ncbi_link": "USP50: 373509"
  },
  {
    "caption": "B IP-IB  analysis of Myc-ACE2  K48-linked ubiquitination  in HEK293T  cells cotransfected with Myc-ACE2  (WT or K788R) and HA-K48, together with shCtrl or shUSP50. Data are representative of three biological replicates.",
    "ncbi_link": "HA: 
Myc: 
ACE2: 59272
USP50: 373509"
  },
  {
    "caption": "C Western blot analysis of Myc-ACE2  in HEK293T  cells transfected with Myc-ACE2  (WT or K788R) and then treated with CHX  (50 μM) as indicated. Data are representative of three biological replicates.",
    "ncbi_link": "Myc: 
ACE2: 59272"
  },
  {
    "caption": "D IP-IB  analysis of K48-Ub  of Myc-ACE2  in HEK293T  cells transfected with Myc-ACE2  (WT or K788R) and then treated with VitC  (5 mM) for 12 hrs, by a specific anti-K48-Ub  antibody. Data are representative of three biological replicates.",
    "ncbi_link": "Myc: 
ACE2: 59272"
  },
  {
    "caption": "G ACE2-KO  Caco-2 cells transfected with ACE2  (WT or K788R) were treated with VitC  (5 mM) for 12 hrs, and then were infected with SARS-CoV-2 GFP/ΔN (MOI = 0.1) for 2 hrs. RT-qPCR was used to analyze SARS-CoV-2 RNA  levels. Data are shown as mean and s.d. of three biological replicates (n = 3). N.S, not significant, ***p < 0.001 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "GFP: 
ACE2: 59272"
  },
  {
    "caption": "D Western blot analysis of hACE2  levels in lung  tissues of hACE2 mice  (n = 6) administrated with VitC  as (B). Data are representative of three biological replicates.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "G  RT-qPCR  analysis of the SARS-CoV-2-Spike  mRNA levels in lung, kidney, liver  and spleen  tissues of hACE2 mice  treated with VitC  and the VSV-Spike  viruses as (F). All graphs show the mean ± SEM for five individual mice  (n = 5). ***p < 0.001 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "ACE2: 59272
Spike: 43740568"
  },
  {
    "caption": "A.Volcano plot showing the fold change (y-axis) versus adjusted (adj.) p-value (x-axis) of the beta cell  transcriptomes between   chow and HFD-fed mice (16 weeks). Genes highlighted in red or green are based on the thresholds of Log2 fold change > 1 and adj. P value < 0.01 (two-tailed paired student's t-test). Genes with >10 fold upregulated expression are labeled with their name. Pbk gene expression is indicated by the arrow. RNAseq  data was available from https://doi.org/10.1371/journal.pone.0213299.t004.",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "L. Pbk KD in INS-1 cells suppresses cell growth. Western blot data showed the decreased Pbk expression level in INS-1 cells with Pbk-targeted shRNA transduction. Cell growth curve was from three independent experimets (n=3). ***P < 0.0001 (Vector:shRNA-#1), *P = 0.0181 (Vector:shRNA-#5) , (Two way ANOVA). M. The role of ectopic expression of Pbk-WT and Pbk-Mut on INS-1 cell growth. Western blot data showed the overexpression of V5-flaged wild type and mutant Pbk in INS-1 cells. Cell growth curve was from three independent experimets (n=3). **P = 0.0069 (Two way ANOVA). ns, not statistically significant difference. ",
    "ncbi_link": "Pbk: 290326"
  },
  {
    "caption": "F.  Islet number in each pancreas section on 11-week-old male PbkKI/KI and PbkWT/WT mice (n=4 for each group). *P = 0.0443 (two-tailed unpaired student's t-test). G. Beta cell mass comparison between 11-week-old male PbkKI/KI and  PbkWT/WT mice  (n=4 for each group). **P = 0.0015 (two-tailed unpaired student's t-test). ",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "K, L. Representative images of double  immuno-staining  for insulin (green) and  BrdU  (red) of pancreas from PbkWT/WT (K) or PbkKI/KI (L) mice with 5 weeks HFD  feeding. Islet area was circled with white dashed line. Nuclei  were labeled by DAPI (blue). Scale bar: 50 μm.",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "E, F. JunD KD in  INS-1 cells using shRNA  upregulated Pbk protein levels (E) and mRNA levels (F).  qPCR data was from three independent experimets (n=3).***P = 0.0001 (shRNA-#1), ***P = 0.0007 (shRNA-#2) (two-tailed unpaired student's t-test). G, H. JunD  KD in PIME cells using shRNA increased  Pbk protein levels (G) and mRNA levels (H). qPCR data was from three independent experimets (n=3).*P = 0.0236 (shRNA-#1), *P = 0.0175 (shRNA-#2) (two-tailed unpaired student's t-test). ",
    "ncbi_link": "JunD: 16478
Pbk: 52033"
  },
  {
    "caption": "N. JunD overexpression in PIME cells suppressed Pbk protein levels (M, Lane 2 vs Lane 1), but did not affect Pbk expression in menin-null PIME cells (M, Lane 4 vs Lane 3).",
    "ncbi_link": "JunD: 16478
menin: 17283"
  },
  {
    "caption": "J, K. The effect of T5224 on the binding of JunD,  menin, HDAC3, and acetylated histone3 at the Pbk  locus in PIME  cells (J) or  INS-1 cells (K). Three independent experimets (n=3). *P = 0.0490 (J, JunD), *P = 0.0479 (J, Menin), *P = 0.0154 (J, HDAC3), **P = 0.0029 (J, Ac-H3), *P = 0.0104 (K, JunD), **P = 0.0024 (K, Menin), ***P = 0.0002 (K, HDAC3), ***P = 0.0001 (K, Ac-H3), (two-tailed unpaired student's t-test). ns, not statistically significant difference.",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "F.  Mouse primary  islets treated with MI-503 for 3 days were subjected ChIP assay to detect the  binding of menin, HDAC3, JunD, as well as histone acetylation  level at the  Pbk locus. Three independent experimets (n=3). *P = 0.0218 (Menin), *P = 0.0145 (HDAC3), *P = 0.0184 (Ac-H3) (two-tailed unpaired student's t-test). ns, not statistically significant difference.",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "G. MI-503 increases  proliferation  of  menin-expressing PIME cells but not menin-null PIME cells. Three independent experimets (n=3). ***P < 0.0001 (Two-way ANOVA).",
    "ncbi_link": "menin: 17283"
  },
  {
    "caption": "K-M.  5 days of MI-503 treatment impacts the expression of Pbk at protein level (K) and mRNA level (L), as well as ki67 mRNA levels (M) in human primary islets  (donor number is four). qPCR data was from three independent experimets (n=3). **P = 0.0036 (L, 10 nM), **P = 0.0024 (L, 50 nM), **P = 0.0073 (L, 100 nM), *P = 0.0237 (M, 50 nM) (two-tailed unpaired student's t-test). ns, not statistically significant difference. ",
    "ncbi_link": "ki67: 4288"
  },
  {
    "caption": "E-L. Representative  images  of insulin (green) and Ki67 (red) double staining on mouse islets with 8 wks MI  treatment (E-H), and insulin  (green) or Pbk  (red)  double staining  on mouse islets (I-L).  Nuclei were labeled by  DAPI (blue). Islet area was circled by white dashed line.  Ki67 and Pbk staining are denoted by white arrows. Scale bars: 50 μm.",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "O, P. GTT data for MI-463 or vehicle treated PbkKI/KI or PbkWT/WT mice (n=3 for each group) on 8 weeks HFD  (O) (*P = 0.0133 (Two way ANOVA), ns, not statistically significant difference.) and AUC of GTT data (P) (*P = 0.0442 (two-tailed unpaired student's t-test), ns, not statistically significant difference.).",
    "ncbi_link": "Pbk: 52033"
  },
  {
    "caption": "Muscles were harvested 7 days after implantation of V Low, V Med, and V High clones or control cells (Ctrl).Gene expression of Pdgfb,Ang1,Ang2,Tgfb1, and Sema3a was quantified by qRT-PCR and expressed as fold-change versus control muscles. Data represent individual values, with mean ± SEM (n = 3 or 4, as indicated); *P < 0.05 and **P < 0.01 by one-way ANOVA with Bonferroni multiple comparisons test, after data normalization by logarithmic transformation. TGF-β1: V Low versus V Med P = 0.0047; V Low versus V High P = 0.0379; Sema3A: V Low versus V High P = 0.0042; V Med versus V High P = 0.0179.",
    "ncbi_link": "Ang1: 11727
Ang2: 11731
Pdgfb: 18591
Sema3a: 20346
Sema3A: 20346
TGF-β1: 21803
Tgfb1: 21803"
  },
  {
    "caption": "Muscles were harvested 7 days after implantation of V Low, V Med, and V High clones or control cells (Ctrl).In situ hybridization for Sema3A (green) and CD31 (red) mRNA, with nuclei staining by DAPI, on frozen muscle sections. The three lower panels represent a higher-magnification of the area in the white square in the top panel, as a merged image and as individual channels: arrows indicate cells expressing both transcripts (yellow), only Sema3A (green), or only CD31 (red). Scale bar = 30 μm.Quantification of the percentage of endothelial cells (CD31+) that express Sema3A (left group) and of Sema3A-expressing cells that are endothelial (CD31+, right group). Data represent the mean ± SEM of 12 individual fields of view from three independent muscles (15-94 nuclei/image, 642 total nuclei). No statistics was applied, as data represent complementary sets.",
    "ncbi_link": "CD31: 18613
Sema3A: 20346"
  },
  {
    "caption": "Relative gene expression was quantified in the ex vivo FACS-purified endothelial cells (CD31+) and NEM (CD11b+) and expressed as fold-change versus the V High group. Data represent individual values, with mean ± SEM (n = 3-7, as indicated); **P < 0.01 by one-way ANOVA with Bonferroni multiple comparisons test, after data normalization by logarithmic transformation; Sema3A: V Low versus V High P = 0.0157.",
    "ncbi_link": "Sema3A: 20346"
  },
  {
    "caption": "Mice, implanted with control cells (Ctrl) or myoblasts expressing low (V Low) or medium (V Med) VEGF levels, were treated with the anti-NRP1A antibody blocking Sema3A/NRP1 binding (AbαNRP1A) or with control IgG2a. Analyses were performed after 1 week.D Tgfb1 gene expression in total skeletal muscles after the different treatments, expressed as fold-change versus the Ctrl IgG2a group. Data represent individual values, with mean ± SEM (n = 3 or 4, as indicated); *P < 0.05 and **P < 0.01 by one-way ANOVA with Bonferroni multiple comparisons test, after data normalization by logarithmic transformation; V Low IgG2a versus Ctrl IgG2a P = 0.0083; V Low IgG2a versus V Low AbαNRP1A P = 0.0315.",
    "ncbi_link": "Tgfb1: 21803"
  },
  {
    "caption": "Relative gene expression of Id1, specifically induced by activated SMAD1/5, and Pai1, specifically induced by activated SMAD2/3, in total muscle tissues 1 week after implantation with V Low-, V Med- and V High-expressing myoblast clones or control cells (Ctrl), expressed as fold-change versus the Ctrl group. Data represent individual values, with mean ± SEM (n = 3 or 4, as indicated); **P < 0.01 and ***P < 0.001 by one-way ANOVA with Bonferroni multiple comparisons test, after data normalization by logarithmic transformation; V Low versus Ctrl P = 0.0002; V Low versus V Med P = 0.005; V Low versus V High P = 0.0016.",
    "ncbi_link": "Id1: 15901
Pai1: 18787"
  },
  {
    "caption": "A-C Endothelial Sema3A expression is directly inhibited by VEGF and stimulated by TGF-β1 in vitro. Mouse aortic endothelial cells were stimulated with increasing doses of recombinant VEGF164 or TGF-β1 for 24 h. The expression of Sema3a and Tgfb1 was quantified by qRT-PCR and expressed as fold-change versus the non-stimulated cells. VEGF dose dependently inhibited Sema3a expression (A), but did not affect that of Tgfb1 (B), while TGF-β1 upregulated Sema3a expression in a dose-dependent fashion (C). Data represent individual values, with mean ± SEM (n = 4); **P < 0.01 and ***P < 0.001 by one-way ANOVA with Bonferroni multiple comparisons test, after data normalization by logarithmic transformation; Sema3A expression upon VEGF stimulation: 40 versus 0 P = 0.0041; TGF-β1 upon VEGF stimulation: no significant differences; Sema3A expression upon TGF-β1 stimulation: 1 versus 0 P < 0.0001; 2.5 versus 0 P < 0.0001; 40 versus 0 P < 0.0001.",
    "ncbi_link": "Sema3A: 20346
Sema3a: 20346
TGF-β1: 21803
Tgfb1: 21803"
  },
  {
    "caption": "D-F Mice received intramuscular injections of adenovirus expressing VEGF (AdVIC) or CD8 control (AdCD8) and were treated on days 4 and 6 after vector delivery with intramuscular injections of Sema3A-Fc (10 mg/kg of average muscle tissue weight) or control Fc protein. (D) Immunofluorescence staining of endothelium (CD31, in red), pericytes (NG2, in green), smooth muscle cells (α-SMA, in cyan), and nuclei (DAPI, in blue), showing vessel density and morphology 1 week after injection of adenoviral vectors alone (no treatment) or after 3 weeks and with Fc or Sema3A-Fc treatment. Scale bar = 50 μm. (E) Quantification of vessel length density (VLD) on the same samples shows that treatment with Sema3A-Fc accelerated stabilization of vessels induced by transient and uncontrolled VEGF expression. Data represent the mean ± SEM of individual images (n) acquired from 3 to 4 muscles/group: Uninjected muscles, n = 72; AdCD8 1 week, n = 68; AdVIC 1 week, n = 53; AdVIC+Fc 3 weeks, n = 78; AdVIC+Sema3AFc 3 weeks, n = 91; **P < 0.01 and ***P < 0.001 by Kruskal-Wallis analysis with Dunn's multiple comparisons test: AdCD8 1 week versus AdVIC+Fc 3 weeks P = 0.0037; all other comparisons indicated P < 0.0001.",
    "ncbi_link": "CD8: 12526///12525
VEGF: 22339"
  },
  {
    "caption": "D-F Mice received intramuscular injections of adenovirus expressing VEGF (AdVIC) or CD8 control (AdCD8) and were treated on days 4 and 6 after vector delivery with intramuscular injections of Sema3A-Fc (10 mg/kg of average muscle tissue weight) or control Fc protein. (F) Immunofluorescence staining of endothelial cells (CD31, in red) and NEM (CD11b, in green) on frozen sections of muscles 3 weeks after injection of adenoviral vectors and with Fc or Sema3A-Fc treatment. White arrows indicate NEM. Scale bar = 50 μm.",
    "ncbi_link": "CD8: 12526///12525
VEGF: 22339"
  },
  {
    "caption": "(A, B) Immunoblot analysis of ATG5-ATG12 protein levels in cortical brain lysates of 13-week-old Atg5flox:CamKIIα-Cre WT/KO mice (WT set to 100%, KO: 28.13±8.18%; p=0.0005, nWT=3, nKO=3, one-tailed unpaired t-test).",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(C,D) Immunoblot analysis of ATG5-ATG12 protein level in striatal brain lysates of 13-week-old Atg5flox:Slc32a1-Cre WT/KO mice (WT set to 100%, KO: 21.71±0.41%; p<0.0001, nWT=3, nKO=3, one-tailed unpaired t-test).",
    "ncbi_link": "Atg5: 11793
Cre: 2777477
Slc32a1: 22348"
  },
  {
    "caption": "Protein levels of p62 are significantly increased in cortical lysates of Atg5flox:CamKIIα-Cre KO mice compared to the WT set to 100% (KO: 4855± 587.4%; p<0.0001, n=4, one-tailed unpaired t-test).",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "Protein levels of p62 are significantly increased in cortical lysates of Atg5flox:CamKIIα-Cre KO mice compared to the WT set to 100% (KO: 4855± 587.4%; p<0.0001, n=4, one-tailed unpaired t-test).",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(G, H) Protein levels of p62 are significantly increased in striatal lysates of Atg5flox:Slc32a1-Cre KO mice compared to the WT set to 100% (KO: 2956± 839.3%; p=0.0072, n=4, one-tailed unpaired t-test).",
    "ncbi_link": "Atg5: 11793
Cre: 2777477
Slc32a1: 22348"
  },
  {
    "caption": "(F, G) PKA R1α (F) and PKA R1β (G) protein levels are significantly increased in cortical brain lysates from 13-week-old Atg5flox:CamKIIα-Cre KO mice compared to the WT set to 100% (KOPKA R1α: 286.1± 50.53%, p=0.005, KOPKA R1β:",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(H, I) PKA R1α (H) and PKA R1β (I) protein levels are significantly increased in striatal lysates of Atg5flox:Slc32a1-Cre KO mice compared to the WT set to 100% (KOPKA R1α: 524.1± 8.35%, p<0.0001, KOPKA R1β:",
    "ncbi_link": "Atg5: 11793
Cre: 2777477
Slc32a1: 22348"
  },
  {
    "caption": "(M, N) Immunohistochemistry analysis of PKA R1α levels in NeuN-posititve neurons in the hippocampus of Atg5flox:CamKIIα-Cre WT/KO mice. Scale bar: 50µm, 20µm (small panels). WT: 54.70±0.693, KO: 89.79±1.831; p<0.0001, two-tailed unpaired t-test. nWT= 64; nKO= 71 neurons from n=3 mice per genotype.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "Immunohistochemistry analysis of PKA R1α levels in GFAP-positive cells in the hippocampus of Atg5flox:CamKIIα-Cre WT/KO mice. Scale bar: 50µm, 30µm (small panels). WT: 63.86±2.477, KO: 61.71±2.653; p=0.5549, two-tailed unpaired t-test. nWT= 45; nKO= 40 cells from n=3 mice per genotype.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "Immunohistochemistry analysis of PKA R1α levels in GFAP-positive cells in the hippocampus of Atg5flox:CamKIIα-Cre WT/KO mice. Scale bar: 50µm, 30µm (small panels). WT: 63.86±2.477, KO: 61.71±2.653; p=0.5549, two-tailed unpaired t-test. nWT= 45; nKO= 40 cells from n=3 mice per genotype.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(Q, R) Immunohistochemistry analysis of PKA R1α in GFAP-positive cells in the hippocampus of Atg5flox:Slc32a1-Cre WT and KO mice. Scale bar: 50µm, 30µm (small panels). WT: 45.28±1.018, KO: 48.50±1.440; p=0.0636, two-tailed unpaired t-test. nWT= 61; nKO= 48 cells from n=3 mice per genotype.",
    "ncbi_link": "Atg5: 11793
Cre: 2777477
Slc32a1: 22348"
  },
  {
    "caption": "(G) Immunohistochemistry for PKA R1α and postsynaptic density marker PSD95 on horizontal brains sections from Atg5flox:CamKIIα-Cre WT/KO mice. White rectangular boxes indicate areas magnified below with arrows indicating PKA R1α and PSD95 colocalization.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(H) Mander's overlap coefficient of PKA R1α and PSD95 colocalization in Atg5flox:CamKIIα-Cre WT/KO hippocampus (WT: 0.29±0.009, KO: 0.40±0.012; p<0.0001, two-tailed unpaired t-test). nWT= 31; nKO= 38 from n=3 mice.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(I) Electron microscopy-based analysis of immunogold-labeled PKA R1α/β on Tokuyasu cryosections of the CA1 neuropil area of the hippocampus of Atg5flox:CamKIIα-Cre KO mice. No immunogold labelling was detected in samples where the PKA R1α/β antibody were omitted (negative control). Scale bar: upper row 50 nm, 500 nm lower picture.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "Co-immunoprecipitation of endogenous PKA R1-β with PKA-Cα from Atg5flox:CamKIIα-Cre WT/KO mouse brain lysates (WT set to 100%, KO: 170.3± 14.88%, p=0.005, one-tailed unpaired t-test, n=3). Input, 1.5% of the total lysate was added to the assay.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "Co-immunoprecipitation of endogenous PKA R1-β with PKA-Cα from Atg5flox:CamKIIα-Cre WT/KO mouse brain lysates (WT set to 100%, KO: 170.3± 14.88%, p=0.005, one-tailed unpaired t-test, n=3). Input, 1.5% of the total lysate was added to the assay.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(A-B) Western Blot analysis of pCREB protein levels in Atg5flox:CAG-CreTmx WT/ KO cultured neurons at DIV14, treated with forskolin (WTDMSO set to 100%, WTForskolin: 214.17± 48.87%, KODMSO: 63.26± 15.85%, KOForskolin: 33.50± 10.84%, pWT DMSO/WT Forskolin=0.042, pWT Forskolin/KO Forskolin=0.002, two-way ANOVA with Tukey's multiple comparisons). n=4. The same lysates were run in parallel to detect pCREB and CREB and normalized to their respective loading control before calculating the pCREB/CREB ratio.",
    "ncbi_link": "Atg5: 11793
Cre: 2777477"
  },
  {
    "caption": "(A-B) Western Blot analysis of PKA substrates carrying RRXS/T motif in primary cortico-hippocampal Atg5flox:CAG-CreTmx WT/KO neurons at DIV14, treated with Forskolin (WTDMSO set to 100%, WTForskolin: 291.85± 17.02%, KODMSO: 152.97± 25.26%, KOForskolin: 182.56± 31.89%, pWTDMSO/WTForskolin: 0.001, pWTForskolin/KOForskolin: 0.033, two-way ANOVA with Tukey's multiple comparisons).",
    "ncbi_link": "Atg5: 11793
Cre: 2777477"
  },
  {
    "caption": "(K-M) Representative STED images and Pearson's colocalization coefficient analysis of SHANK3 (K) and CASKIN1 (L) and PSD95 in Atg5flox:CamKIIα-Cre:Ai9 WT/KO neurons. Scale bar: 5µm, 1µm (small panels). WTSHANK3: 0.324±0.022, KOSHANK3: 0.415±0.024; p=0.0067, two-tailed unpaired t-test. nWT=46, nKO=46. WTCASKIN1: 0.255±0.024, KO CASKIN1: 0.326±0.025; p=0.0432, two-tailed unpaired t-test. nWT=39, nKO=43 from n=2 independent experiments.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
CASKIN1: 268932
Cre: 2777477
SHANK3: 58234"
  },
  {
    "caption": "(C,D) Analysis of GLUR1 fluorescent levels at the spines of 10-11 week-old Atg5wt/wt:Ai9 and Atg5flox/flox:Ai9 mice injected with CamKIIα-Cre AAV into the hippocampus. Scale bar: 5µm. GLUR1 level at PSD95-positve spines were assessed measuring mean gray values after background subtraction (WT: 64.55±7.988%, KO: 99.14±6.863%; p=0.0029, two-tailed unpaired t-test). nWT=13, nKO=14 images from n=3 mice (>31 dendritic spines analyzed per each mouse). sp, spine.",
    "ncbi_link": "Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(G) Representative fluorescence images of Atg5flox:CAG-CreTmx WT/KO neurons transfected with eGFP or eGFP-ATG5 and immunostained for GLUR1, PSD95 and GFP. (H) The overexpression of eGFP-ATG5 in Atg5flox:CAG-CreTmx KO neurons diminished the of GLUR1/PSD95 colocalization compared to the eGFP-overexpressing KO neurons (KOeGFP: 70.07±1.473%, KOeGFP-ATG5: 65.42±1.721%,; p=0.048, two-tailed unpaired t-test). nKO+GFP=42, nKO+GFP-ATG5=50 images from n=5. (I, J) The coexpression of eGFP-PKA R1α and eGFP-PKA R1β in cultured Atg5flox:CAG-CreTmx WT neurons results in significantly increased colocalization between GLUR1 and PSD95 compared to the eGFP-expressing neurons (WT: 42.30±2.453%, KO: 51.32±2.624%, p=0.014, two-tailed unpaired t-test). nWT+GFP=46, nWTGFP+PKA R1 OE=46 images from n=3. Analysis in H, J is performed using a unbiased custom-written Plugin for ImageJ.",
    "ncbi_link": "eGFP: 
GFP: 
ATG5: 9474
Atg5: 11793
Cre: 2777477
PKA R1α: 19084
PKA R1β: 19085"
  },
  {
    "caption": "(K-M) GCAMP7f responses to tetanic stimulation (four tetani, 100 APs at 100Hz, 3s interval) in cell bodies of CamKIIα-Cre-transduced primary cortico-hippocampal Atg5wt:wt/Ai9 (WT) and Atg5flox:flox/Ai9 (KO) neurons expressing mCamKIIα-jGCaMP7f and treated either with DMSO (K) or with 10 µM CNQX for 5 min (L). Autophagy deficient cells showed significantly increased facilitation of GCAMP7f signal to electrical stimulation (ΔF/Fpeak1) compared to the WT, a phenotype which was blocked by the application of CNQX (WTDMSO: 0.28± 0.12, WTCNQX: -0.07± 0.03, KODMSO: 3.74± 0.86, KOCNQX: -0.014± 0.13, p WT DMSO/ KO DMSO<0.0001, pKO DMSO/KO CNQX<0.0001, two-way ANOVA with Tukey's multiple comparisons test). nWT DMSO= 25, nWT CNQX= 27, nKO DMSO= 33, nKO CNQX= 30 neurons from n=3.",
    "ncbi_link": "GCaMP7f: 
Atg5: 11793
CamKIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "C, Box and whisker plots showing mean pixel intensities for ColE9* K469CAF647 fluorescence per cell measured for the indicated cells and condition used, whiskers represent minimum and maximum mean pixel intensity, box shows 1st and 3rd quartile with the median shown as a line. From left-to-right: E. coli JM83 cells; E. coli btuB deletion strain showing loss of all ColE9* K469CAF647 cell-associated fluorescence; E. coli JM83 cells in the presence of CCCP; E. coli JM83 cells following trypsin treatment showing significant ColE9* K469CAF647 fluorescence remains associated with cells indicative of import; E. coli JM83 cells treated with CCCP and trypsin showing the complete loss of internalised ColE9* K469CAF647 fluorescence. n, number of cells used, typically from 2-4 biological replicates. ****, indicates a t value <0.05 in a student T-test as a statistically significant result, ns indicates no significant difference as determined by student T-test.",
    "ncbi_link": "btuB: "
  },
  {
    "caption": "(A) Hematoxylin and Eosin (H&E) staining of WT and K14ΔNLef1 HF from back skin at 11.5 weeks (early anagen). White arrowheads: ectopic SG and epidermal cysts. Data information Scale bars: 50 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(B) Tail epidermal whole-mounts from WT and K14ΔNLef1 mice labelled with Fabp5, Krt15 and counterstained with Dapi. Data information: Scale bars: 50 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(C) Average signal intensity of ΔNLef1 binding sites detected by a Lef1 antibody (red) as compared to input alone (grey) and negative control (Neg. Ctl., black). DNA motif analysis revealed Lef1 classical consensus sequence. Representative plots of ChIP-Seq reads aligned to the Vgll4, Runx1 and Gata6 loci.",
    "ncbi_link": "Gata6: 14465
Lef1: 16842
Runx1: 12394
Vgll4: 232334"
  },
  {
    "caption": "(D) Heat-map (Pearson correlation) of differentially expressed genes (DEG) between different micro-dissected regions (IFE, HF and SG) from WT mice (left panel) ΔNLef1 Chip-seq data show ΔNLef1 direct transcriptional targets in black (right panel).",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(E) Gene Set Enrichment Analysis comparing gene location of ΔNLef1 peaks and SG gene expression signature.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(F) RT-qPCR analysis of Gata6 in WT and K14ΔNLef1 primary keratinocytes transfected with siRNA targeting ΔNLef1 or a scrambled sequence (scr.). Data are means ± SEM of three independent wells. Data information Statistical analyses were performed with an ordinary one-way ANOVA: (ns) not significant; (*) p-value < 0.05; (***) p-value < 0.0005.",
    "ncbi_link": "Gata6: 14465
Lef1: 16842"
  },
  {
    "caption": "(G) RT-qPCR analysis of Gata6 in human SebE6E7 sebocytes transfected for 48h with a mock plasmid or a Lef1- or ΔN34Lef1-expressing plasmid. ∆N34Lef1 is the human ortholog of murine ∆N32Lef1, which is expressed in K14∆NLef1 transgenic mice Data are means ± SEM of three independent experiments. Data information: Statistical analyses were performed with an ordinary one-way ANOVA: (ns) not significant; (*) p-value < 0.05; (***) p-value < 0.0005.",
    "ncbi_link": "Gata6: 2627
Lef1: 51176
Lef1: 16842"
  },
  {
    "caption": "(H) Dorsal skin sections of WT and K14ΔNLef1 mice stained for Krt14 and Gata6. Data information Scale bars: 50 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(I) Heat-maps of DEG from WT- or K14ΔNLef1-unfractionated (all) or sorted (Itga6+Cd34-, basal; Itga6+Cd34+, HFSC) keratinocytes in comparison with IFE, SG, and HF gene signatures ranked from high to low expression.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(J) Heat-map depicting similarities, as Pearson's correlation coefficient, between DEG from keratinocytes from WT or K14ΔNLef1 mice and IFE vs SG vs HF transcriptome analysis (left panel). Additional correlation with ΔNLef1 Chip-seq data is depicted in the right heat-map.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(A) Sections of WT embryonic skin at different HF stages stained for Gata6, Lef1, Sox9 and counterstained with Dapi. Black asterisks indicate overexposed areas of nonspecific Lef1 staining in the suprabasal epidermis. Quantification of the percentage of cells labelled for both Gata6 and Lef1, or Gata6 and Sox9 in stages 4-5 HF are shown (upper right panel). Data are means ± SD and were obtained from 9 HF from 3 mice. (B) Sections of E18.5 WT and Lef1-/- mouse skin stained for Lef1 and Gata6. Deletion of Lef1 does not impair Gata6 expression. Data information: Scale bars: 50 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(C) Sections of WT and K14ΔNβcateninER (K14ΔNβ-catER D2 and D4 strains) adult dorsal skin stained with antibodies against Krt14 and Gata6. Topical treatment with 1 or 6 doses of 4OHT activates β-catenin leading to anagen induction and ectopic hair follicles but not Gata6 expression. Data information: Scale bars: 50 μm.",
    "ncbi_link": "β-cat: 12387
βcatenin: 12387
ER: 13983///13982"
  },
  {
    "caption": "(D) Sections of E18.5 WT and K14Cre/βCat Flox(ex3)/+ mouse skin stained for Sox9 and Gata6. Activation of Wnt/β-catenin signaling during epidermis development does not induce Gata6 expression but results in ectopic expression of the HFSC marker Sox9. Data information: Scale bar: 25 μm.",
    "ncbi_link": "Cre: 2777477
β-catenin: 12387
βCat: 12387"
  },
  {
    "caption": "(A) Bright-field images of whole-mount WT and Gata6 cKO epidermis, showing abnormal SG upon loss of Gata6. Quantification of hypotrophic SG in WT, heterozygous (Het) and Gata6 cKO epidermal whole-mounts. Data are boxplots with indication of means. Box limits are minimum and maximum values. An average of 165 HF per mouse (from 3 to 4 mice per genotype) was analyzed. (*) p-value < 0.05; (**) p-value < 0.005; unpaired Student's t-test. Data information: Scale bars: 50 μm.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(B) Schematic representation of plasmid constructs used for in utero lentiviral infection. Whole-mounts or sections of adult infected epidermis with empty vector (EV) or Gata6-ires-GFP (G6OE) lentivirus were stained for GFP and Fasn. In vivo overexpression of Gata6 leads to ectopic Fasn expression in the HF/SG unit. White dotted lines define SG, and yellow dotted lines define a cyst. Note that the cyst is mostly negative for Fasn in agreement with its SD-like phenotype. White arrows indicate GFP-positive infected cells. These cells are stained with Fasn only in G6OE condition. H&E-stained skin from G6OE mice shows a cyst with SG elements in the HF unit (black arrows). Staining for Gata6 (both endogenous and exogenous) shows that Gata6 expression occurs in a limited number of cells (representative image in upper right panel). Bottom left graph shows quantification of the percentage of clones labelled for both Fasn and GFP in the SG, HF and IFE compartments. Data are means ± SD and originate from 4 EV mice and 8 G6OE mice (average of 11 clones per mouse). (C) Whole-mounts adult infected epidermis with EV or G6OE lentivirus stained with LipidTOX. Ectopic Gata6 cells are not stained with LipidTOX indicating an incomplete sebaceous maturation. Data information: Scale bars: 50 μm.",
    "ncbi_link": "GFP: 
Gata6: 2627"
  },
  {
    "caption": "(D) Lineage tracing experiments in Gata6EGFPCreERT2:Rosa26-fl/STOP/fl-tdTomato (Gata6creER ROSA-dTom) mice. A single dose of 4OHT was injected in pregnant females at E16.5. Tail skin from pups was collected at P13. Representative example of whole-mount epidermis showing tdTomato labelled cells counterstained with Dapi (top left panel). Right panels show the different Z-stacks related to this whole-mount. Gata6 progenies are mainly found in the upper SG/JZ. Localization of Gata6 progenies (dTomato+) was quantified in 20-26 pilosebaceous units per mouse (N=4 mice) (bottom left panel). Data are means ± SD. As a control, quantification was also performed in Rosa26-fl/STOP/fl-tdTomato (ROSA-dTom) mice that were treated similarly to Gata6creER ROSA-dTomato mice. Data information: Scale bar: 25 μm.",
    "ncbi_link": "dTom: 
dTomato: 
EGFP: 
tdTomato: 
ERT2: 827836
Cre: 2777477
cre: 2777477
ER: 13983
Gata6: 14465
ROSA: 14910
Rosa26: 14910"
  },
  {
    "caption": "(A) Sections of mouse skin tumors were stained with antibodies to Gata6 and Krt14. A papilloma tumor found in WT mice treated with DMBA and TPA (left panel), is compared with sebaceous tumors found in K14ΔNLef1 mice (right panels). Data information: Scale bars: 100 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(B) Tumor burden and tumor incidence in DMBA-treated K14ΔNLef1 (n=11) and K14ΔNLef1:cKO (n=8) mice. (***) p-value < 0.001; Wilcoxon matched-pairs signed rank test. Data information: Data are means ± SEM.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(C) Representative H&E-stained tumors of K14ΔNLef1 and K14ΔNLef1:cKO mice with quantification of each tumor type relative to the total number of tumors in each group (middle panel) and as the average absolute number of tumors per mice (right panel). A total of 268 tumors were analyzed. 143 tumors were found in 7 K14ΔNLef1 mice (103 sebaceous tumors and 40 papillomas), while 125 were found in 5 K14ΔNLef1:cKO mice (55 sebaceous tumors and 70 papillomas). (**) p-value < 0.005, Student's t-test. Data information: (C) Scale bar: 1 mm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(A) Heat-map highlighting differentially expressed genes (DEG) between WT and Gata6 cKO keratinocytes Gata6 direct transcriptional targets from Chip-Seq data are shown in dark grey.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "(C) MSI analysis performed on skin tumors from DMBA-treated K14ΔNLef1 and K14ΔNLef1:cKO mice (5 mice in each group). Representative microsatellite profiles of K14ΔNLef1 and K14ΔNLef1:cKO tumors. Peak heights were normalized to the highest peak in each microsatellite profile to obtain the relative frequency of each allele for 5 different markers. \"0\" indicates the position of the highest peak in bp. (*) p-value < 0.05; (**) p-value < 0.001; paired t-test.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(D) Representative immunohistochemistry stainings against Mlh1 performed on skin tumors from DMBA-treated K14ΔNLef1 and K14ΔNLef1:cKO mice. 4 mice were included in each group. A technical control is displayed (without primary antibody incubation). Semi-quantitative analysis of Mlh1 staining and statistical analysis (χ2 test) were performed. Data information: Scale bar: 250 μm.",
    "ncbi_link": "Lef1: 16842"
  },
  {
    "caption": "(A) Normal human scalp skin sections stained with Gata6 and PanKeratin antibodies. Endogenous Gata6 expression is found in the JZ, upper SG and SD. As in mouse skin, Gata6 is not expressed in sweat glands (SwG). (B) Representative sections of human skin tumors stained with Gata6 and PanKeratin antibodies. Quantification of the percentage of Gata6-positive tumors within each histopathological group (middle left panel) and quantification of the percentage of Gata6-positive cells within each positive sample (middle right panel). Note that the least positive sample showed about 3% of Gata6-positive cells. The analysis was performed on 73 different tumor samples. SSC : squamous cell carcinoma, SCAP: syringocystadenoma papilliferum, EMPD: extramammary Paget's disease, nod./superf./scler. BCC: nodular/ superficial/ sclerodermiform basal cell carcinoma, Steatocystoma M.: steatocystoma multiplex, FSCH: folliculosebaceous cystic hamartoma. Heat-map displaying the -log(p-value) of χ2 test computed between the different tumor types (bottom left panel). (C) Gata6 expression (measured in Transcripts Per Million, TPM) in human SCC (n=6), BCC (n=6) and sebaceous carcinoma (n=14) samples from (North et al, 2018). Data are means ± SD. (**) p-value ≤ 0.005, Student's t-test. Data information: (A and B) Scale bars: 100 μm. ",
    "ncbi_link": "Gata6: 2627"
  },
  {
    "caption": "(A) Differentiation status (poor, moderate or well-differentiated), circumscription (not infiltrative, focally infiltrative or infiltrative), log10 total number of mutations and Gata6 mutations in 32 human sebaceous carcinomas (SebC) separated in 3 subgroups: pauci-mutational, MSI-related and UV-related For Gata6 mutations, the most deleterious mutation is displayed. n.a.: not assessed.",
    "ncbi_link": "Gata6: 2627"
  },
  {
    "caption": "(C) Gata6 expression (measured in Transcripts Per Million, TPM) in human pauci-mutational (pauci-mut) SebC (n=4), MSI-related SebC (n=4), UV-related SebC (n=5) samples. Data are means ± SD. (*) p-value ≤ 0.05, Student's t-test.",
    "ncbi_link": "Gata6: 2627"
  },
  {
    "caption": "(D-F) Graphs showing the number of mutations per megabase (Mutations/Mb) (D), the number of Somatic Single-Nucleotide Variants (SSNV) (E) and indel (F) of Gata6mut (n=3) or Gata6wt (n=6) MSI-related SebC (left panels) and of Gata6mut (n=3) or Gata6wt (n=7) UV-related SebC (right panels). Data are means ± SD.",
    "ncbi_link": "Gata6: 2627"
  },
  {
    "caption": "(G) Heat-map displaying the mean expression level of MMR genes (measured in TPM) in Gata6wt (n=10) and Gata6mut (n=3) SebC.",
    "ncbi_link": "Gata6: 2627"
  },
  {
    "caption": "B, Mouse embryonic fibroblasts genetically modified using CRISPR to introduce a GFP sequence immediately after the start codon of Syne2 display fluorescence at the nuclear envelope.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "A, CRISPR-modified cells (Brightfield, left) that express GFP-nesprin-2 (middle) and mCh-LAC (right) show nesprin (orange arrow) but not lamin accumulation at the front of the nucleus as it is deformed through a narrow constriction. B, Quantification of intensity of GFP-nesprin-2 and mCh-LAC, normalized to the intensity at the sides. Error bars correspond to the standard deviation. Constriction: n=19 cells over 5 biological replicates, 15 µm: n= 27 over 6 biological replicates. A Wilcoxon signed-rank test is used to compare matched samples, stars (*P < 0.05, **P < 0.01) denote comparisons to the measurement at the side, and pounds (#P < 0.05, ##P < 0.01) denote a comparison to the \"before\" time point.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "Assessment of receptor channel activity using MK-801 inhibition kinetics. Representative current traces from oocytes expressing either wild-type (WT) or GluN1-E698C/GluN2B-L795C mutant receptors in response to 10 nM MK-801 during agonist application. Responses were scaled to the current amplitude obtained before MK-801 application. Inset, mono-exponential fits of MK-801 wash-in and wash-out. Note the strikingly faster kinetics in mutant receptors, both at the onset and offset of MK-801",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Zinc, ifenprodil and pH dose-response curves of wild-type (WT) GluN1/GluN2B receptors and mutant GluN1-E698C/GluN2B-L795C receptors. For comparison, zinc and ifenprodil dose-response curves of GluN1/GluN2B receptors lacking the whole GluN2B NTD (GluN1 WT/GluN2B-delNTD) are also shown (dashed lines; data from Rachline et al, 2005)",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Spermine (200 µM, pH 6.3) potentiation of WT GluN1/GluN2B and mutant GluN1-E698C/GluN-L795C receptors. Spermine (200 µM, pH 6.5) sensitivity is also shown for WT GluN1/GluN2B receptors and receptors lacking either the GluN1 (GluN1-delNTD/GluN2B WT) or GluN2B (GluN1 WT/GluN2B-delNTD) NTD (data from Mony et al, 2011)",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Glutamate and glycine dose-response curves of WT GluN1/GluN2B receptors and mutant GluN1-E698C/GluN2B-L795C receptors",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Representative recordings of patches containing one single wild-type (WT) or GluN1-E698C/GluN2B-L795C receptor. The bottom trace is an expanded view. C, closed channel; O, open channel",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Single channel properties (equilibrium channel open probability, mean open time, mean closed time) of the WT and super-active GluN1-E698C/GluN2B-L795C receptors",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "Closed (left) and open (right) time histograms for WT (upper panels) or super-active GluN1-E698C/GluN2B-L795C (lower panels) receptors. Closed time histograms were best fit with 5 exponentials, whereas open time histograms were best fit with 2 exponentials (see Online Methods and Appendix Fig S8). Smooth lines are associated exponential fits",
    "ncbi_link": "GluN1: 24408
GluN2B: 14812"
  },
  {
    "caption": "(B) 48h post-transfection of HeLa-CIITA  cells with siRNAs targeting NDP52, T6BP, OPTN, and p62, AR  expression was analyzed using  Western Blot. Tubulin  was used as control. The results are representative of at least 3 independent experiments and correspond to AR  expression levels of the experiment in Figure 1B, left panel.",
    "ncbi_link": "NDP52: 10241
CIITA: 4261
OPTN: 10133
p62: 8878
T6BP: 8887"
  },
  {
    "caption": "(C) Monitoring of Gag-specific T cell  activation. HeLa-CIITA cells were treated as indicated above and transfected with a plasmid encoding Gag-LC3. Left panel, a representative experiment is shown (+/- SD of three technical replicates). Right panel, three biological replicates are combined and presented as mean percentage (+/- SD). The y-axis represents the relative percentage of IFNγ  spots reported to the secretion of IFNγ  by the CD4+ T cell clones incubated with the siCTRL-treated HeLa-CIITA  and set to 100%. The mean  T cell activation levels of the three experiments using siCTRL or siT6BP were (100, 195, 119) and (35, 53, 38) IFNγ+ spots, respectively. 5000 T cell clones were seeded per well in technical triplicates. Data information: For all ELISPOT  experiments, the background secretions of IFNγ  by CD4+ T cells  co-cultured with mock-treated HeLa-CIITA  cells were used as negative controls and subtracted. CTRL: control. Wilcoxon's test; the symbols correspond to ** p<0.01 and # p>0.05 comparing each experimental conditions solely with its internal control (siCTRL).",
    "ncbi_link": "CIITA: 4261
Gag: 155030
LC3: 64862///362245
T6BP: 8887"
  },
  {
    "caption": "(D) Left panel, as in Figure 1B right panel, but using DNA encoding Gag-LC3, Gag-LC3G120A, or Gag. With Gag-LC3, Gag-LC3  G120A or Gag  antigens, the mean  T cell  activation levels using siCTRL or siT6BP were (199, 435, 384), (91, 141, 119) and (343, 415, 385) or (98, 273, 171), (27, 50, 19) and (97, 148, 131) IFNγ+ spots, respectively. 5000 T cell  clones were seeded per well in technical triplicates. Three biological replicates are combined and presented as mean percentage (+/- SD). Right panel, influence of T6BP  silencing on peptide presentation by Hela-CIITA  cells. The cognate peptide was added exogenously (gag2, 0,1µg/mL) on siRNA-treated cells (2h, 37°C), washed and  T cell  activation monitored using IFNγ-ELISPOT. The mean T cell activation levels using siCTRL or siT6BP were (100, 45, 42) and (71, 45, 33) IFNγ+ spots, respectively. 1000 T cell  clones were seeded per well in technical triplicates. Three biological replicates are combined and presented as mean percentage (+/- SD). Data information: For all ELISPOT  experiments, the background secretions of IFNγ  by CD4+ T cells co-cultured with mock-treated HeLa-CIITA  cells were used as negative controls and subtracted. CTRL: control. Wilcoxon's test; the symbols",
    "ncbi_link": "CIITA: 4261
Gag: 155030
LC3: 64862///362245
T6BP: 8887"
  },
  {
    "caption": "(E) As in (D) but using cDNA encoding HCMV pp65  antigen (left panel) or pp65  peptide (0,5µg/mL; right panel) and a pp65-specific CD4+ T cell  line. Results of three independent experiments are represented. The mean T cell  activation levels using siCTRL or siT6BP  and pp65  DNA were (66, 106, 99) and (39, 50, 33) IFNγ+ spots, respectively. For the peptide: siCTRL or siT6BP: (185, 317, 415) and (163, 292, 381) IFNγ+ spots, respectively. 1000 or 2000  T cell  clones were seeded per well in technical triplicates. Data information: For all ELISPOT  experiments, the background secretions of IFNγ   by CD4+ T cells  co-cultured with mock-treated HeLa-CIITA  cells were used as negative controls and subtracted. CTRL: control. Wilcoxon's test; the symbols correspond to ** p<0.01 and # p>0.05 comparing each experimental conditions solely with its internal control (siCTRL).",
    "ncbi_link": "CIITA: 4261
T6BP: 8887
pp65: 3077579"
  },
  {
    "caption": "(D) T6BP  silencing affects the formation of stable MHC-peptide complexes. HeLa-CIITA  cells were transfected as above and pulse-labeled with 35S-Met/Cys  for 30 min, washed and chased for 4h at 37°C. MHC-II  molecules were then immunoprecipitated  using TÜ36  antibody and analyzed on SDS-PAGE  after incubation of the immunoprecipitated protein complexes with SDS at 95°C (B: boiled) or room temperature  (NB: non-boiled) to visualize α, β and Ii chains and SDS  resistant αβ dimers, respectively. The bands corresponding to α, β and Ii chains are indicated. The arrow indicates the SDS-resistant stable HLA αβ heterodimers. This gel is representative of two independent experiments.",
    "ncbi_link": "CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "(A) MHC-II  and T6BP expressions  were assessed using confocal microscopy. HeLa-CIITA  cells were transfected with control and T6BP-silencing siRNAs. 48h post-treatment, MHC-II  and T6BP  were detected using L243 and anti-T6BP  antibodies, respectively, and revealed with species specific secondary antibodies. Nuclei  were stained  using DAPI. (B) Quantitative analysis using in-house ImageJ script displaying distance of each MHC-II+ vesicles  to the nucleus  and number of vesicles  per cell. At least 20,000 vesicles  from 160 cells corresponding to five biological replicates were analyzed. Right panel, quantification in the siCTRL cells of the colocalization  between MHC-II+ and T6BP+ dots using Pearson's coefficient where the dotted lines (at 0.5) indicate the limit under which no significant  co-localization is measured (number of cells = 54). Data information: In graphs representing the number of vesicles  per cells, each dot displayed corresponds to a single cell. Within the violin plots, continuous and dotted lines correspond to medians and quartiles, respectively. Scale bars: 2μm. CTRL: control. Mann-Whitney's test; * p<0.05; ** p<0.002; *** p<0.0003; **** p<0.0001; # p>0.05.",
    "ncbi_link": "CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "(A) CD74  expression was assessed using Western Blot. HeLa-CIITA  cells were transfected with siCTRL and siT6BP. 48h post treatment, the Iip33 CD74  isoform, a degradation product (Iip16), T6BP  and actin  were detected using indicated antibodies. Left panel, a representative Western Blot experiment is shown. Right panel, expressions levels five biological replicates were quantified using ImageJ and are presented as mean of ratios (+/-SD) of CD74  to actin  used as control housekeeping gene expression.",
    "ncbi_link": "CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "(D) CD74  expression is partially recovered by blocking lysosomal  acidification. As in (A), following siRNA transfection of Hela-CIITA  cells, CD74  expression was assessed. The last 16h prior to harvesting, cells were treated with chloroquine  (CQ) or epoxomicin  (Epo). Left panel a representative experiment is shown, membranes were blotted  using anti-T6BP, -CD74  and -actin  antibodies. The different degradation fragments of CD74  are indicated (Iip33, Iip22 and Iip16). Right panel, expression levels of Iip33 (top) and Iip16 (bottom) were quantified in three biological replicates using ImageJ and are presented as mean of ratios of each fragment to actin  (+/-SD). Data information: (D) One-way Anova statistical test combined with Bonferronis multiple comparison test was applied. Dotted lines indicate statistically significant differences between conditions.",
    "ncbi_link": "CIITA: 4261"
  },
  {
    "caption": "(E Analysis of CD74 proteolysis. HeLa-CIITA  cells were transfected with siCTRL and siT6BP. 48h post treatment, cells were pulsed for 30 min with 35S-Met/Cys, washed and chased for 1, 2 and 4h. HLA-DR/CD74  complexes were first immunoprecipitated  using Tü36 antibody (E) Samples were boiled and analyzed using  SDS-PAGE. The bands corresponding to CD74  isoforms (Iip41 and Iip33) and the cleavage products (Iip16) are indicated. (E right panel) Iip16 expression was quantified using ImageJ and presented as a percentage of Iip16 normalized to the highest quantity of Iip16 detected after 1h of chase in the control condition. Results are representative of two biological replicates. Ii: invariant chain (CD74); CTRL: control.",
    "ncbi_link": "CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "F). Analysis of CD74 proteolysis. HeLa-CIITA  cells were transfected with siCTRL and siT6BP. 48h post treatment, cells were pulsed for 30 min with 35S-Met/Cys, washed and chased for 1, 2 and 4h.  HLA-DR/CD74  complexes were immunoprecipitated  using VICY1 antibody (F). Samples were boiled and analyzed using SDS-PAGE. The bands corresponding to CD74  isoforms Iip33) Results are representative of two biological replicates. Ii: invariant chain (CD74); CTRL: control.",
    "ncbi_link": "CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "(A-B) CANX co-immunoprecipitates with T6BP  in model and professional APCs. Endogenous T6BP  was immunoprecipitated  from HeLa-CIITA, B (DG-75) and dendritic-like (KG-1, DC) cells. The input, the flow through (FT) and the immunoprecipitation  (IP) fractions were analyzed by Western blot using the indicated antibodies. Bottom panels, control IPs  using the beads without antibody (IP  CTRL) are presented for each IP. (B) As in (A) but using anti-CANX  Ab for the IP. For A and B, one representative experiment out of three biological replicates is shown.",
    "ncbi_link": "CIITA: 4261"
  },
  {
    "caption": "(C) CANX interacts  with T6BP  using proximity ligation assay (PLA). 48h post-transfection with the indicated siRNAs, HeLa-CIITA  cells were fixed, stained  with anti-T6BP  and anti-CANX  antibodies and proximity revealed using PLA  (Duolink). Nuclei  were stained  using DAPI. Top panel, two representative fields are shown. Bottom panel, quantitative analysis using ImageJ displaying the number of PLA  per cell. The continuous line indicates the mean (+/-SEM). PLA  were quantified in at least 130 cells corresponding to three biological replicates. Scale bars: 10μm. CTRL: control; Mann-Whitney's test; ***: p<0.0003.",
    "ncbi_link": "CIITA: 4261"
  },
  {
    "caption": "(D) Calnexin interacts  with T6BP  through its cytosolic  tail. HeLa-CIITA  cells were transfected with a plasmid encoding the GST-tagged transmembrane  (TM) and cytosolic  (CytoTail) domains of CANX  (GST-TM-CytoTail-CANX) or the vector not encoding TM-CytoTail-CANX  as control and immunoprecipitated with anti-GST  antibodies. The input, FT, the wash and the IP  fractions were analyzed by Western blot  and revealed using the indicated antibodies. One representative experiment out of three biological replicates is shown.",
    "ncbi_link": "GST: 
CANX: 821
CIITA: 4261"
  },
  {
    "caption": "(E) Silencing of T6BP  does not influence CANX  expression levels while silencing of CANX  reduces the level of CD74  expression. HeLa-CIITA  cells transfected with the indicated siRNAs and samples analyzed, 48h post transfection, by Western blot  with the indicated antibodies. These western blot  results are representative of at least three biological replicates.",
    "ncbi_link": "CANX: 821
CIITA: 4261
T6BP: 8887"
  },
  {
    "caption": "B. Overall survival of 107 patients without alterations versus 37 patients with ROCK1 and/or ROCK2 gene amplification, significantly increased mRNA or truncation mutation from TCGA research network. Survival p value determined by Log-Rank test.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "C, D. Log2 median-centered ROCK1 or ROCK2 RNA expression in normal (n=39) vs PDAC (n=39), normal (n=5) vs pancreatic adenocarcinoma (PAC) (n=12), or normal (n=6) vs pancreatic carcinoma (PC) (n=11) samples from indicated studies. Exact p values determined by Mann-Whitney test.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "E. ROCK1 and ROCK2 mRNA expression in human PDAC (n=146) from the TCGA research network. Significance (p value) of slope deviation from 0 determined by Deming regression.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "H. Survival analysis of Pdx1-Cre; LSL-KRasG12D/+; LSL-Trp53R172H/+; LSL-ROCK2:ER (RKPC) mice without (n=21) or with conditional ROCK activation with tamoxifen citrate (n=19). Survival p value determined by Log-Rank test.",
    "ncbi_link": "ER: 13983///13982
KRas: 16653
Pdx1: 18609
ROCK2: 19878
Trp53: 22059"
  },
  {
    "caption": "B. Schematic representation of ROCK domains (RBD, Rho binding domain; PH, pleckstrin homology domain; CR, cysteine-rich). Conditionally-activated human ROCK1, human ROCK2 and GFP control fusion proteins (EGFP, enhanced green fluorescent protein; hbER, estrogen receptor hormone binding domain) were expressed in KPflC mouse PDAC cells and blotted with anti-GFP antibody.",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "C. KPflC cells expressing GFP:ER, ROCK1:ER or ROCK2:ER fusion proteins were treated for 24 h with EtOH vehicle or 1 µM 4HT in the presence or absence of 1 µM or 10 µM H1152. Immunoblotting shows endogenous ROCK1 and ROCK2, ER-fusions, and phosphorylation of MLC2 (T18S19). Total MLC (MRCL3/MRLC2/MYL9) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were blotted as loading controls.",
    "ncbi_link": "ER: 13983///13982
ER: 2100///2099
ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "E. Cell proliferation determined by Ki67 immunofluorescence. Scale bar: 20 µm.F. Quantification of cell number at the collagen matrix surface per 0.046 mm2 field. Means ± SEM (n=30), one-way ANOVA with multiplicity adjusted exact p value by post hoc Dunnett's multiple comparison test.G. Ki67 positive cell percentages at the surface and within the collagen matrix. Means ± SEM (n=30; n=12 for GFP:ER/Matrix), one-way ANOVA with multiplicity adjusted exact p value by post hoc Dunnett's multiple comparison test.",
    "ncbi_link": "ER: 2100///2099"
  },
  {
    "caption": "A. Volcano plots of RNA sequencing data of genes that pass a threshold false discovery rate (FDR) < 5%, with log10 fold-change (FC) in expression in 4HT treated ROCK1:ER expressing cells relative to GFP:ER expressing cells (left) or 4HT treated ROCK2:ER expressing cells relative to GFP:ER expressing cells (right) versus log10 adjusted p value (n=3). ROCK1:ER+4HT vs GFP:ER+4HT; 3828 genes. ROCK2:ER+4HT vs GFP:ER+4HT; 4481 genes.",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "E. Mmp10 mRNA levels relative to Gapdh determined by qPCR following treatment with EtOH vehicle (-) or 1 µM 4HT for 24 h (left). Means ± SEM (n=4), p value by unpaired t test. Mmp10 mRNA levels relative to Gapdh determined by qPCR following treatment with EtOH vehicle (-), 1 µM 4HT or 4HT + 1 µM H1152 ROCK inhibitor for 24 h (right). Means ± SEM (n=3), one-way ANOVA with multiplicity adjusted exact p value by post hoc Tukey multiple comparison test.F. Mmp13 mRNA levels relative to Gapdh determined by qPCR following treatment with EtOH vehicle (-) or 1 µM 4HT for 24 h (left). Means ± SEM (n=4), p value by unpaired t test. Mmp13 mRNA levels relative to Gapdh determined by qPCR following treatment with EtOH vehicle (-), 1 µM 4HT or 4HT + 1 µM H1152 ROCK inhibitor for 24 h (right). Means ± SEM (n=3), one-way ANOVA with multiplicity adjusted exact p value by post hoc Tukey multiple comparison test.",
    "ncbi_link": "Gapdh: 
Mmp10: 17384
Mmp13: 17386"
  },
  {
    "caption": "A. Confocal microscope images of ROCK1:ER-expressing cells co-stained for F-actin, MMP10 (left) or MMP13 (right) and DAPI following treatment with vehicle or 1 µM 4HT for 24 h. Multiple z-planes were used to generate x-z and y-z images. Scale bar = 5 µm.",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093"
  },
  {
    "caption": "C. Representative stained gel of ultracentrifuge-enriched microvesicle protein from GFP:ER or ROCK1:ER-expressing cell-conditioned media following treatment with vehicle (-) or 1 µM 4HT for 24 h (top). Absolute arbitrary unit values for total microvesicle protein levels in stained gels (bottom). Means ± SEM (n=4), p value by ratio paired t-test.",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093"
  },
  {
    "caption": "D. Transmission electron microscopy of ultracentrifuge-enriched microvesicles (top center), and immunogold labeling of MMP10 in ROCK1:ER 4HT-treated microvesicles, indicated by red arrows (top right).",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093"
  },
  {
    "caption": "D. Cell proliferation determined by Ki67 immunofluorescence. Scale bar: 20 µm.E. Ki67 positive cell percentages at the collagen matrix surface. Means ± SEM (n=20; n=19 for GFP:ER/vehicle, n=18 for GFP/GM6001), one-way ANOVA with multiplicity adjusted exact p value by post hoc Tukey multiple comparison test.F. Ki67 positive cell percentages in collagen matrix. Means ± SEM (n=20; n=8 for GFP:ER/ vehicle, n=10 for GFP:ER/GM6001, n=17 for ROCK1:ER/GM6001, n=15 for ROCK2:ER/GM6001), one-way ANOVA with multiplicity adjusted exact p value by post hoc Tukey multiple comparison test.",
    "ncbi_link": "ER: 2100///2099
ROCK1: 6093
ROCK2: 9475"
  },
  {
    "caption": "A. Survival analysis of Pdx1-Cre; LSL-KRasG12D/+; LSL-Trp53R172H/+; (KPC) mice without (n=13) or with Fasudil treatment (n=13). Survival p-value determined by Gehan-Breslow-Wilcoxon test.",
    "ncbi_link": "Cre: 
KRas: 16653
Pdx1: 18609
Trp53: 22059"
  },
  {
    "caption": "p53 has been show to response with a series of undamped pulse to ionizing irradiation leading to cell cycle arrest while intrinsic DNA damage during cell cycle does not induce regular pulsatile p53 and subsequent gene expression programs. Schematic representations of p53 dynamics in both cellular conditions are shown.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Induction of selected p53 target genes after DNA damage induction in A549 wild-type and p53 knockdown cells. RNA levels were measured by qRT-PCR before and 3h after treatment with 10 Gy R. Fold changes relative to basal levels are shown for each cell line.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Amount of p53 bound to indicated target gene promoters before (basal, grey) and 3 h (red), 6 h (blue) and 9 h (orange) after DNA damage (10 Gy IR) as measured by ChIP. The amount of bound p53 was calculated as percentage of input and normalized to the time-point of the first p53 peak at 3 h. Individual data points (mean values of triplicate quantification in qRT-PCR measurements) from 3-4 biological repeats are shown as dots, mean values are displayed as black horizontal lines. Dashed lines serve as guide to the eyes. We could not detect p53 binding above IgG controls at the published p53 response element in the PPM1D promoter (indicated by n.d.)",
    "ncbi_link": "PPM1D: 8493"
  },
  {
    "caption": "We quantified promoter activity of BAX (B, sustained archetype) and PPM1D (C, pulsatile archetype) before (basal, grey) and 3 h (red), 6 h (blue) and 9 h (orange) after irradiation with 10 Gy IR and inhibition of the second p53 pulse by Chk2 inhibition. Left panel: The percentage of cells with active TSS, subdivided into populations with strong (> 75% of TSS, solid colors) and weak (<75% of TSS, shaded colors) activity, is shown as stacked bar graphs, the mean fraction of active promoters is indicated above each bar. Right panel: Distributions of calculated transcription rates at active TSS are presented for each time point as probability density estimates (PDF, see Data Visualization section). The fraction of active promoters was reduced at 6 h and 9 h after irradiation; the transcription rate was not notably affected.",
    "ncbi_link": "BAX: 581
PPM1D: 8493"
  },
  {
    "caption": "We quantified promoter activity of MDM2 (E, transient archetype) and CDKN1A (F, transient archetype) before (basal, grey) and 3 h (red), 6 h (blue) and 9 h (orange) after irradiation with 10 Gy IR and sequential Nutlin-3 treatment. Left panel: The percentage of cells with active TSS, subdivided into populations with strong (> 75% of TSS, solid colors) and weak (<75% of TSS, shaded colors) activity, is shown as stacked bar graphs, the mean fraction of active promoters is indicated above each bar. Right panel: Distributions of calculated transcription rates at active TSS are presented for each time point as probability density estimates (PDF, see Data Visualization section). The relative fraction of active promoters strongly increased, changing transient to sustained archetypes. The transcription rate increased as well both compared to basal levels and to previous experiments with pulsatile p53 dynamics (inset, fold change relative to IR alone for each time point).",
    "ncbi_link": "CDKN1A: 1026
MDM2: 4193"
  },
  {
    "caption": "The p53-K370 methylase Smyd2 was down-regulated in a clonal stable A549 cell line expressing a corresponding shRNA. Transcript levels were measured in wild type and knockdown cells by qRT-PCR. Mean levels and standard deviation from technical triplicates are indicated.",
    "ncbi_link": "Smyd2: 56950"
  },
  {
    "caption": "Promoter activity of CDKN1A (E) and MDM2 (F) were quantified in Smyd2 knockdown cells before (basal, grey) and 3 h (red), 6 h (blue) and 9 h (orange) after DNA damage (10 Gy IR). Left panel: The percentage of cells with active TSS, subdivided into populations with strong (> 75% of TSS, solid colors) and weak (<75% of TSS, shaded colors) activity, is shown as stacked bar graphs, the mean fraction of active promoters is indicated above each bar. Right panel: Distributions of calculated transcription rates at active TSS are presented for each time point as probability density estimates (PDF, see Data Visualization section). We measured a higher fraction of active promoters upon damage compared to A549 wild type cells (Fig 3), while transcription rates remained unchanged.",
    "ncbi_link": "CDKN1A: 1026
MDM2: 4193
Smyd2: 56950"
  },
  {
    "caption": "The p53-K382 methylase Set8 was down-regulated in a clonal stable A549 cell line expressing a corresponding shRNA. Transcript levels were measured in wild type and knockdown cells by qRT-PCR. Mean levels and standard deviation from technical triplicates are indicated.",
    "ncbi_link": "Set8: 387893"
  },
  {
    "caption": "Promoter activity of CDKN1A (E) and MDM2 (F) were quantified in Set8 knock-down cells before (basal, grey) and 3 h (red), 6 h (blue) and 9 h (orange) after DNA damage (10 Gy IR). Left panel: The percentage of cells with active TSS, subdivided into populations with strong (> 75% of TSS, solid colors) and weak (<75% of TSS, shaded colors) activity, is shown as stacked bar graphs, the mean fraction of active promoters is indicated above each bar. Right panel: Distributions of calculated transcription rates at active TSS are presented for each time point as probability density estimates (PDF, see Data Visualization section). We measured a higher fraction of active promoters upon damage compared to A549 wild type cells (Figure 3), while transcription rates remained unchanged.",
    "ncbi_link": "CDKN1A: 1026
Set8: 387893
MDM2: 4193"
  },
  {
    "caption": "E. RT-qPCR of Axin2 in bEnd.3 cells treated with NDP (200 ng/ml), isotype control or F4L5.13 (1200 ng/ml) and transfected with control, Tspan12 or Fzd4 siRNAs. Data are presented as mean ± SD, n=3 technical replicates. Data is representative of two independent experiments. F. Time course of phosphorylated Disheveled-3 (p-DVL3) and ßcatenin protein levels in bEnd.3 cells treated with 30nM of F4L5.13 or NDP. Histogram represents the ratio of the DVL3 phosphorylation levels over total DVL3 protein and ßcatenin levels over ß-Tubulin measured by densitometry of independent experiments. Data are presented as mean ± SEM, n=4-6 (*p<0.05 as compared with NT). Significance was calculated by one-way ANOVA with Bonferroni's multiple comparisons test (*p<0.05 as compared with NT). ",
    "ncbi_link": "Axin2: 12006
Fzd4: 14366
Tspan12: 269831"
  },
  {
    "caption": "E. F4L5.13 rescues barrier function defects in Tspan12-/- mice as shown by an increased expression of the tight junction component CLDN5 and decreased expression of the EC fenestration component PLVAP. IB4-Alexa647 was used to stain ECs. Scale bars: 100 µm.",
    "ncbi_link": "Tspan12: 269831"
  },
  {
    "caption": "D. Flat-mounted retinas of adult Tspan12-/- mice injected systemically with sulfo-NHS-biotin show that F4L5.13 partially restored BRB function. PECAM was used to stain endothelial cells. Images are representative of 4 retinas per group. Scale bar: 500 µm.",
    "ncbi_link": "Tspan12: 269831"
  },
  {
    "caption": "E. Maximum intensity projection of adult Tspan12-/- retinas after mice were injected with F4L5.13 or isotype control. Endothelial cells were stained with IB4-Alexa 647. Images are representative of 4 retinas per group. Scale bar: 100 µm.",
    "ncbi_link": "Tspan12: 269831"
  },
  {
    "caption": "D)  HEK293  cells were genetically engineered to knockout RIG-I, MDA5, or both, and subsequently subjected to retroviral  transduction to stably express FLAG-LGP2 or an empty vector (EV). Correct gene editing and intact type I IFN responsiveness was validated by  SDS-PAGE and immunoblotting  using the indicated antibodies (n=2). *, non-specific band.",
    "ncbi_link": "FLAG: 
RIG-I: 23586
LGP2: 79132
MDA5: 64135"
  },
  {
    "caption": "E) Cells generated in (D) were transfected with siCtrl or siADAR1. The  type I IFN  response and ADAR1 knockdown efficiency was monitored 78h post-transfection as in (B). Data are means ± s.d. from a representative of four biological replicate experiments.",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "F) Cells generated in (D) were transfected with siCtrl (siC) or siADAR1 (siA). Protein lysates were prepared 78h post-transfection, followed by SDS-PAGE and immunoblotting using the indicated antibodies (n=2).",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "G)  HEK293 WT cells and FLAG-LGP2-expressing HEK293 cells were transfected with siCtrl or siADAR1  and subsequently plated on coverslips for immunofluorescence. Cells were fixed, permeabilized and stained  72h post-transfection with anti-FLAG (red) and anti-IRF3 (green) antibodies. Nuclei  were  stained with DAPI (blue). Scale bar is 50 μm. Total nuclei  (>450 nuclei  per experimental condition) and  IRF3-positive nuclei  were counted using semi-automated software analysis and plotted as percentage IRF3-positive nuclei of total nuclei per field of view (a representative of three biological replicate experiments is quantified). The boxplot indicates the interquartile range as a box, the median as a central line, and the whiskers extend from the minimum to the maximum value. Statistical analyses were performed using unpaired two-tailed Mann-Whitney U tests. ns, not significant; ****, p<0.0001.",
    "ncbi_link": "FLAG: 
ADAR1: 103
LGP2: 79132"
  },
  {
    "caption": "A) HEK293  cells were genetically engineered to knockout ADAR1 using CRISPR/Cas9. Cells were treated for 24h with recombinant type I IFN to upregulate  ADAR1 p150 and  ISG60 to confirm correct gene editing and type I IFN  responsiveness, respectively. Protein lysates were analyzed by SDS-PAGE  followed by  immunoblotting  using the indicated antibodies (n=3).",
    "ncbi_link": "CRISPR: 
ADAR1: 103
Cas9: 69900935"
  },
  {
    "caption": "B) ADAR1-knockout HEK293 cells (clone 1) were co-transfected with an empty vector (EV) or a FLAG-LGP2-encoding vector (LGP2) combined with a vector encoding GFP-tagged ADAR1 p110 or p150. Cells were harvested 72h post-transfection and the type I IFN  response was monitored by RT-qPCR analysis of  IFN-β  and IFIT1 expression, normalized to ACTB. Data are means ± s.d. from a representative of four biological replicate experiments.",
    "ncbi_link": "FLAG: 
GFP: 
ACTB: 60
ADAR1: 103
ADAR1 p110: 103
LGP2: 79132
IFIT1: 3434
IFN-β: 3456"
  },
  {
    "caption": "C) ADAR1-knockout cells (clone 1) were transfected as in (B). Protein lysates were analyzed by SDS-PAGE followed by  immunoblotting  using the indicated antibodies (n=4).",
    "ncbi_link": "ADAR1: 103"
  },
  {
    "caption": "A) ADAR1-knockout HEK293 cells (clone 1) were modified with a  lentiviral-based inducible system to express FLAG-LGP2 WT or a FLAG-LGP2 RNA binding mutant (K138E/R490E/K634E, denoted as \"KRK mutant\") in a  doxycycline-regulated manner. Cells were treated 72h with  doxycycline  (dox). Protein lysates were analyzed by SDS-PAGE  and  immunoblotting  using the indicated antibodies (n=3). iEV = inducible empty vector; iLGP2  = inducible LGP2.",
    "ncbi_link": "FLAG: 
ADAR1: 103
LGP2: 79132"
  },
  {
    "caption": "E) MDA5-knockout HEK293 cells, were transfected with an ADAR1-targeting siRNA (siADAR1) or a control siRNA (siCtrl) and 8h later with an empty vector (EV) or a vector encoding the indicated WT, truncation, or point mutant(s) of MDA5. Cells were harvested 72h post-siRNA transfection and the type I IFN  response was monitored by RT-qPCR analysis of IFIT1  and ISG15  transcript  expression, normalized to ACTB. Data are means ± s.d. from a representative of two biological replicate experiments.",
    "ncbi_link": "ACTB: 60
ADAR1: 103
MDA5: 64135
IFIT1: 3434
ISG15: 9636"
  },
  {
    "caption": "B) HEK293  WT or ADAR1-knockout cells (clone 1) were transiently transfected with an empty vector (EV) or a vector encoding the indicated WT, truncation, or point mutant(s) of  LGP2. Cells were harvested 72h post-transfection and the  type I IFN response was monitored by RT-qPCR analysis of IFN-β and IFIT1 transcript expression, normalized to  ACTB. Data are means ± s.d. from a representative of three biological replicate experiments.",
    "ncbi_link": "ACTB: 60
ADAR1: 103
LGP2: 79132
IFIT1: 3434
IFN-β: 3456"
  },
  {
    "caption": "A) Kaplan-Meier plots showing overall survival  of ADARlow and ADARhigh patients stratified by DHX58 levels in bladder cancer (BLCA; n=407), breast cancer (BRCA; n=1099) and sarcoma (SARC; n=263) TCGA datasets. Median cut-offs were used for patient  stratification and logrank test P values are shown.",
    "ncbi_link": "ADAR: 103
DHX58: 79132"
  },
  {
    "caption": "B) CAL27 cells transduced with doxycycline-inducible shRNAs targeting  ADAR1 or GFP (negative control) were treated with doxycycline  and transfected with two independent siRNAs targeting LGP2  (siLGP2 #1 or #2) or a control siRNA (siCtrl). To determine  cell confluency at 120h post-transfection, cells were fixed, stained  with Crystal Violet, and imaged. Images of a representative experiment are shown (n=3). C) Crystal Violet was extracted from stained cells (B) and the dye intensity was quantified using a colorimetric assay (OD590). OD590 values of doxycycline-treated cells were normalized to the OD­590 values of untreated cells. Quantification of data from three independent experiments is shown as mean ± s.d.. Statistical analysis was performed using ordinary two-way ANOVA with Tukey's post hoc test. ns, not significant; *, p<0.05; **, p<0.01; ****, p<0.0001.",
    "ncbi_link": "GFP: 
ADAR1: 103
LGP2: 79132"
  },
  {
    "caption": "A) HT29  cells were treated with or without 300 nM  5-AZA-CdR  for 2 days and subsequently washed and transfected with the indicated siRNAs. Cells were harvested 72h post-transfection and the  type I IFN  response was analyzed by RT-qPCR  analysis of  IFN-β, IFIT1, and  ISG15 transcript  expression, normalized to  ACTB. B) LIM1215 cells were treated with or without 300 nM 5-AZA-CdR for 2 days and subsequently washed and transfected with the indicated siRNAs. Cells were harvested 72h post-transfection and the type I IFN response was analyzed as in (A). C) LIM1215 cells were treated with 250 nM palbociclib or a DMSO  control for 7 days. Three days after treatment initiation, cells were transfected with the indicated siRNAs and cultured for an additional 72h. The type I IFN  response was monitored as in (A). Data information: Data from three biological independent experiments are shown with mean ± s.d.. Statistical analysis was performed using ordinary two-way ANOVA with Tukey's post hoc test. ns, not significant; *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001. ",
    "ncbi_link": "ACTB: 60
IFIT1: 3434
IFN-β: 3456
ISG15: 9636"
  },
  {
    "caption": "Cells expressing a nearly functional FtsZ-mVenus fluorescent fusion as their sole copy of ftsZ were monitored after transition into carbon starvation. Two low motile MG1655 strains, one (wild-type) containing clpX and one without (ΔclpX), were grown in M9 glucose to steady-state. At time zero, M9 media without glucose was flushed through device. Cells rapidly ceased elongation as measured by phase contrast imaging at 2 minute intervals. Fluorescent images were taken every hour throughout to measure both total Ftsz-mVenus per cell and localization patterns Thin individual lines show the total fluorescent per cell in a single lineage (wild-type in solid blue, n = 154. ΔclpX in dotted red, n = 144). Thick solid lines are the time average across individual lineages for each subset (wild-type in blue, ΔclpX in red). After starvation, cells containing clpX degrade FtsZ faster than cells which do not. Fluorescent signals are normalized to the average value for their respective subset at time 0 Distributions of cellular fluorescence for each subset at times corresponding to the top panel. Cellular fluorescence varies widely as total FtsZ per cell is a function of cell size; a typical size distribution is shown at left. FtsZ concentration is roughly constant at steady-stat Student\"s t-test P value shown for when distributions differ with significance level α = 0.01. Representative images from cells in a single lineage with and without clpX. Wild-type strains may contain the characteristic FtsZ ring at midcell after shift down but it dissipates after several hours. ΔclpX strains display an abnormal FtsZ localization pattern even in steady-state. After shift down, the FtsZ may disassemble and reform along the cell body in distinct puncta. Image timing corresponds to the abscissa in the top",
    "ncbi_link": "clpX: 945083"
  },
  {
    "caption": "Genetically induced titration of PdhR in a pdhR mutant reintroduced lag commensurate with expression level for a given TI feedrate (f = 0.38 mmol/g/h). Induction level corresponds to the amount of doxycycline (max - 50 ng/uL, half - 10 ng/uL, and zero 0 ng/uL) added at the onset of starvation. The TI feedrate is abbreviated as f (units: mmol glucose/g dry cell weight/hour). Wild-type lag (from Figure 2A empirical fit) is indicated by the dotted grey line. Lag time reduced with synthesis levels of titrated FtsZ in the wild-type strain at f = 0.31-0.32 mmol/g/h. Lag time increased with titrated synthesis of ClpX in wild-type cells at f = 0.43-0.45 mmol/g/h",
    "ncbi_link": "ClpX: 945083
FtsZ: 944786
PdhR: 944827
pdhR: 944827"
  },
  {
    "caption": "B Induction of NF-κB targets in Jurkat T cells in response to 20 ng/ml TNF treatment for 1, 2, and 4 hours as measured by RT-qPCR. Target values were normalized to GAPDH and are reported as fold change relative to basal expression. Data are presented as mean ± standard deviation (SD) of 3 biological replicates.",
    "ncbi_link": "GAPDH: 2597
NF-κB: 4792"
  },
  {
    "caption": "D Maximum intensity projections of smFISH fluorescence microscopy z-stacks of basal Jurkat T cells stained for the indicated genes. Nfkbia, Tnfaip3, Tnf, and  Il6 were labeled with Quasar 670, and Il8  and Csf2 were labeled with  fluorescein. All images were filtered as described in Materials and Methods. Brightness and contrast were enhanced for visualization. Scale bars: 10 μm.",
    "ncbi_link": "Csf2: 1437
Il8: 3579
Il6: 3569
Nfkbia: 4792
Tnf: 7124
Tnfaip3: 7128"
  },
  {
    "caption": "A Maximum  intensity projections of  smFISH fluorescence microscopy z-stacks of Jurkat T cells  stained for the indicated genes after 1-hour (Nfkbia, Tnfaip3, Tnf,  Il8) or 4-hour (Il6, Csf2) treatment with 20 ng/mL TNF. Nfkbia, Tnfaip3, Tnf, and Il6 were labeled with Quasar 670, and Il8  and Csf2 were labeled with fluorescein. All images were filtered as described in Materials and Methods. Brightness and contrast were enhanced for visualization. Scale bars: 10 μm. B Bar graphs of mean of smFISH distributions before and after TNF treatment for the indicated genes. Cells were combined from three replicates (Nfkbia 1h; Tnfaip3 1h; Tnf  1h, 2h; and  Il6 2h, 4h) two replicates (Nfkbia 2h) or one replicate (Tnfaip3 2h; Il8 1h, 2h; Csf2 2h, 4h). Basal data are same as in Fig. 1E. Error bars indicate bootstrapped 95% CIs for the samples in (C). Significant differences indicated by non-overlapping CIs. C ",
    "ncbi_link": "Csf2: 1437
Il8: 3579
Il6: 3569
Nfkbia: 4792
Tnf: 7124
Tnfaip3: 7128"
  },
  {
    "caption": "B-C Burst size  (B) and burst frequency (C) parameter fits from the two-state model in the basal state and after treatment with 20 ng/mL  TNF for 1, 2 or 4 hours. Error bars indicate bootstrapped 95% CIs. Significant differences indicated by non-overlapping CIs. The fit for Nfkbia (1h TNF) was unstable and thus is not reported",
    "ncbi_link": "Nfkbia: 4792"
  },
  {
    "caption": "C Bar graphs of mean mRNA level for basal condition, 1h TNF, 1h TNF + 4h pretreatment with 300nM A-485, and 1h TNF+62.5nM JQ1 cotreatment measured by smFISH for  Tnfaip3 (left) and Tnf (right). Cells were combined from two replicates (Tnfaip3 A-485, JQ1; Tnf A-485) or one replicate (Tnf JQ1). Error bars indicated bootstrapped 95% CIs. Samples with non-overlapping CIs are significant. D Change in enrichment of total and Serine-5-phosphorylated RNAPII  after 20ng/mL TNF treatment for 1 hour with 62.5nM  JQ1 measured by  ChIP-qPCR and shown as % input (non-IP control) normalized to the uninhibited control for each gene. Data are presented as mean for two biological replicates. E ",
    "ncbi_link": "Tnf: 7124
Tnfaip3: 7128"
  },
  {
    "caption": "a-c, Expression of CD45RO and CCR7 (a), CD45RO and CD27 (b), CD27 and CD28 (c) on peripheral blood CD8 T cells of three participants [P1 (heterozygous mutation), P2 (homozygous mutation) and P3 (heterozygous) for the c.192G>C mutation in the DJ-1 gene]. d-g, Expression of CD57 (d), PD-1 (e), EOMES (f) and T-bet (g) on peripheral blood CD8 T cells of three participants. The enlarged number in the corresponding gate represents the corresponding percentage out of the parent population. h",
    "ncbi_link": "DJ-1: 11315"
  },
  {
    "caption": "b-c, Percentages of CD44low CD62Lhigh (Tn) (b) and CD44high CD62Llow (Tem) (c) cells among total CD8 T cells of spleen and pLNs from young and 45-wk-old Dj-1 KO and WT littermates (young KO, n=5; young WT, n=5; 45-wk-old KO, n=8; 45-wk-old WT, n=6; for 45-wk-old mice, data pooled from 2 independent experiments).",
    "ncbi_link": "Dj-1: 57320"
  },
  {
    "caption": "e, Percentages of Ki-67+ cells among total CD8 T cells. f, Percentage of Ki-67+ cells among splenic CD8 Tn, Tem and Tcm in 45-wk-old Dj-1 KO and age- and sex-matched WT mice. g",
    "ncbi_link": "Dj-1: 57320"
  },
  {
    "caption": "b, Percentages of KLRG1+ CD8 T cells derived from 45-wk-old Dj-1 KO and WT BM cells within young Dj-1 KO (n=4) or WT recipients (n=5). c, Percentages of KLRG1+ among CD8 Tem derived from 45-wk-old Dj-1 KO and WT BM cells within young Dj-1 KO or WT recipients. d d, Percentages of PD-1+ population among CD8 T cells derived from 45-wk-old Dj-1 KO and WT BM cells within young Dj-1 KO (n=4) or WT recipients (n=5).",
    "ncbi_link": "Dj-1: 57320"
  },
  {
    "caption": "(A) Transcription at GAL3 is visualized by addition of PP7 loops at the 5' of GAL3 in budding yeast. Example trace of the quantified fluorescence intensity of the transcription site. Traces are binarized to determine on (active) and off (inactive) times.",
    "ncbi_link": "GAL3: 851572"
  },
  {
    "caption": "(B) Histogram of GAL3 on time (burst duration) for cells with wt and mutated UAS, respectively, reveals shorter on times for mutated UAS. Errors indicate SE of 3 experiments, n = 324 cells UASwt, n = 250 cells UASmut. (C) Histogram of GAL3 off times. Errors indicate SE of 3 experiments. ",
    "ncbi_link": "GAL3: 851572"
  },
  {
    "caption": "(G) Example traces of quantified fluorescence intensity at the transcription site for 5'PP7 and 3'MS2 at GAL3.",
    "ncbi_link": "GAL3: 851572"
  },
  {
    "caption": "(I) Distribution of number of nascent RNAs at the transcription site determined by smFISH. The distribution of UASwt does not fit a Poisson distribution (grey line), supporting that GAL3 is not constitutively transcribed, but is transcribed in bursts. Example image in shown, yellow arrows indicate TSs. Scale bars: 5 μm. n = 11,839 cells. (J) for cells with UASmut. The distribution of UASmut fits a Poisson distribution, indicating that GAL3-UASmut is transcribed with random initiation of individual polymerases, similar to constitutive genes. n = 10,616 cells.",
    "ncbi_link": "GAL3: 851572"
  },
  {
    "caption": "(A) Competitive binding experiments were performed to determine relative affinity of Gal4 to UASwt (green) and UASmut (blue) motifs. Gal4 occupancy on UASwt Cy3/Cy5 DNA was determined by measuring protein induced fluorescence enhancement (PIFE) on 51 bp oligos containing either Gal4 UASwt or UASmut site 1 bp away from Cy3 fluorophore).",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(C) Comparison between relative affinities of Gal4 UASwt versus UASmut in naked or nucleosomal DNA shows 4.3 ± 1.1x difference in KD from naked DNA and 6.8 ± 1.7x from nucleosomal DNA. n = 3. Error bars indicate SD.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(D) Experimental setup for smFRET experiments to measure Gal4 binding at nucleosomal DNA. Gal4 binds to site 8 bp into nucleosome. A FRET pair in the entry/exit region provides readout on binding events (one fluorophore on DNA, one on histone). In the absence of Gal4, nucleosomes are in the high FRET state. A Gal4 binding event traps nucleosome in low FRET state.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(E) Gal4 affinity to nucleosomes containing UASwt or UASmut sequences gives S1/2 of 7.2 ± 0.8 nM and 48.9 ± 10.8 nM, respectively. n = 3. Error bars indicate SD.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(F) Example smFRET traces showing Gal4 binding to UASwt in nucleosomal DNA at two different Gal4 concentrations. States are determined using HMM fit. (G) Same as F but for UASmut. ",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(H) Binding-rates of Gal4 are concentration dependent, but are similar for UASwt and UASmut: kon UASwt = 0.011 ± 0.002 s-1 nM-1, kon UASmut = 0.009 ± 0.001 s-1 nM-1. n = 2 for all, except n = 4 for UASwt 10 nM Gal4 and n = 3 for UASwt 20 nM Gal4. Error bars indicate SD.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(I) The dissociation-rate of Gal4 at UASwt is ~5-fold slower compared to the UASmut: koff UASwt = 0.20 ± 0.01 s-1, koff UASmut = 0.92 ± 0.05 s-1. n = 2 for all, except n = 4 for UASwt 10 nM Gal4 and n = 3 for UASwt 20 nM Gal4. Error bars indicate SD.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(J) Histogram of Gal4 dwell time to nucleosomal DNA containing UASwt and UASmut sequences. n = 11 for UASwt, n = 8 for UASmut. Error bars indicate SE.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(K) Scatter plot showing the average number of nascent RNA at TS (from smFISH) vs affinity of Gal4 to different UAS sequences in nucleosomal DNA (from in vitro measurements). In vivo transcription levels correlate with in vitro affinity of Gal4, but transcription saturates above wildtype sequence. UAS sequences are shown in the box. For mean number of nascent RNA from smFISH, n = 2 for UASconsensus, UAS-2C, UAS-8T and n = 8 for UASwt, UASmut and errors indicate SEM. For in vitro affinity measurements, n = 3 and errors indicate SD.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "Profiles of nucleosome midpoint positions by MNase-seq experiments. Samples were digested with the indicated MNase concentrations in both raffinose (raf) and galactose (gal) containing media. Midpoints of nucleosomes are smoothed by 31 bp. In galactose the stable nucleosomes move away from the Gal4UAS, creating space for an additional fragile nucleosome (indicated by arrow).",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(A) Simultaneous imaging of Gal4 binding kinetics in vivo using single-molecule tracking and RNA imaging of the GAL10 target gene. Gal4 is tagged with a HALO-tag, which covalently binds to the dye JF646. Transcription of the target gene GAL10 is visualized by PP7-loops.",
    "ncbi_link": "HALO: 
GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(B) Example image of a cell, showing the GAL10 TS (arrow, left panel), single molecules of Gal4 (arrows, middle panel) and an overlay (right panel). Scale bar: 2 μm.",
    "ncbi_link": "GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(C) Example kymograph of a cell. Upper panel (PP7-GAL10) shows the position of the TS over time. Middle panel (Gal4-HALO) show tracks of Gal4. Data is in white, colored lines show analyzed tracks. Lower panel shows overlay, showing colocalization of some the Gal4 tracks to the GAL10 TS. Scale bar: 1 μm.",
    "ncbi_link": "HALO: 
GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(D) Survival probability of the duration of Gal4 tracks (after displacement thresholding) at 200 ms interval from cells grown in raffinose (n = 258 tracks in 30 cells) or galactose (n = 346 tracks in 25 cells). Lines show bi-exponential fit, indicating 2 Gal4 populations. Inset shows data in semi-logarithmic plot. (E) Residence time of the fast and slow component of the fits from (D). The slow component changes between conditions. Error bars indicate 95% CI. ",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(F) Survival probability of Gal4 residence times that colocalize with GAL10 TS (<250nm), showing that Gal4 with long residence time colocalizes with GAL10. Data was taken at 1s interval and shows overlap between 267 Gal4 tracks and 83 GAL10 tracks, representing 458 bound molecules. Line shows exponential fit, with mean of 12.3s ± 0.83s. Errors indicate 95% CI.",
    "ncbi_link": "GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(A) Schematic of 3D orbital tracking of GAL10 TS. Scale bar: 2 μm.",
    "ncbi_link": "GAL10: 852307"
  },
  {
    "caption": "(B) Example trace of Gal4 binding and GAL10 transcription in the same cell.",
    "ncbi_link": "GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(C) Autocorrelation of Gal4. The exponential fit shows an average dwell time of 34.8 ± 0.5s. n = 19 traces. Shaded area and errors indicate SEM.",
    "ncbi_link": "Gal4: 855828"
  },
  {
    "caption": "(D) Autocorrelation of GAL10. The fit of 2 linear lines reveals a burst duration of 152.4 ± 2.3s. n = 19 traces. Shaded area and errors indicate SEM.",
    "ncbi_link": "GAL10: 852307"
  },
  {
    "caption": "(E) Cross correlations for Gal4-GAL10 RNA (blue) and Gal4-RNR2 RNA (grey, negative control). Asymmetry and positive temporal shift of the cross correlation function is consistent with a 79.5 ± 0.2 second delay between the middle of Gal4 and GAL10 signals (n = 19 traces), which is not seen in the negative control (n = 8 traces). Shaded areas and errors indicate SEM.",
    "ncbi_link": "GAL10: 852307
Gal4: 855828
RNR2: 853427"
  },
  {
    "caption": "(F) Schematic of the different signal durations of Gal4 binding and GAL10 transcription. Gal4 binding overlaps with the GAL10 transcription for 14.1s.",
    "ncbi_link": "GAL10: 852307
Gal4: 855828"
  },
  {
    "caption": "(A) Example trace of PP7-GAL10 transcription in 2% galactose.",
    "ncbi_link": "GAL10: 852307"
  },
  {
    "caption": "Control- or IRE1-siRNA transfected HEK293T cells were stimulated by either PA (500 µM) or TG (600 nM) for 4 hours. Protein lysates were analyzed by western blotting using specific antibodies for pFMRP, FMRP, pIRE1, IRE1 and β-Actin. pFMRP/FMRP fold induction is depicted above the blots (n=4 biological replicates).",
    "ncbi_link": "IRE1: 2081"
  },
  {
    "caption": "MEF cells were transfected with either empty vector, EGFP-FMRP or 3xFLAG-IRE1 plasmids then pre-treated either with vehicle (dimethyl sulfoxide, DMSO) or AMG-18 (25 µM; 1 hour) followed by TG (600 nM) stimulation for 4 hours. Protein lysates were analyzed by western blotting using specific antibodies for pFMRP, FMRP, pIRE1, IRE1 and β-Actin. pFMRP/FMRP fold induction is depicted above the blots (n=4 biological replicates).",
    "ncbi_link": "EGFP: 
FLAG: 
IRE1: 2081
FMRP: 14265"
  },
  {
    "caption": "Fmr1+/+ and Fmr1-/- mice were injected with AAV_PCSK9 and fed with 16 weeks of WD. Residential PM were stained with Oil Red O (ORO) and imaged (n=7 mice per group; Scale bar = 50 µm).    Apoe-/- mice were fed with WD (12 weeks) and injected with vehicle (DMSO) or AMG-18 (30 mg/kg/day) in the last 4 weeks of WD. Residential PM were stained with ORO and imaged (n=5 mice per group; Scale bar = 50 µm).  ",
    "ncbi_link": "Apoe: 11816
Fmr1: 14265
PCSK9: 100102"
  },
  {
    "caption": "A-E In vitro and in vivo efferocytosis experiments, where percentage of macrophages F4/80+ (red) that ingested apoptotic cells (AC) labeled with carboxyfluorescein succinimidyl ester (CFSE)+ (green) were reported as % efferocytosis. (A) BMDMs were transfected with Fmr1- or control-siRNA and incubated CFSE-labeled AC for the indicated hours (n=4 biological replicates). (B) Fmr1+/+ and Fmr1-/- BMDMs were treated with PA (500 µM) for 6 hours and then incubated with CFSE-labeled ACs for 4 hours (n=4 biological replicates). (C) Fmr1+/+ and Fmr1-/- mice were fed WD (16 weeks) and injected intraperitoneally with CFSE-labeled AC (1.5 hours), followed by PM elicitation (n=4-5 mice per group). (D) BMDM were pre-treated either with vehicle (DMSO) or AMG-18 (5 µM) for 1 hour then incubated with CFSE-labeled ACs for 4 hours (n=3 biological replicates). (E) C57BL/6 mice were injected with AMG-18 (30 mg/kg) or vehicle (DMSO) for 8 hours, followed by intraperitoneal injection with CFSE-labeled ACs for 1.5 hours and PM elicitation (n=4 mice per group).",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "F-G In vitro continuous efferocytosis experiments, where macrophages were stained for F4/80+ (red), AC were labeled with CFSE (AC-1; green) or Violet (AC2; violet). % continuous efferocytosis was determined by the ratio of F4/80+, CFSE+ and Violet+ (triple positive) cells to total F4/80+ and CFSE+ (double positive) cells. (F) Fmr1+/+ and Fmr1-/- BMDM were incubated with AC-1 for 2 hours, and after 2 hours interval, incubated with AC-2 for 2 more hours (n=4-3 biological replicates). (G) BMDM were pre-treated either with vehicle (DMSO) or AMG-18 (5 µM) for 1 hour, incubated with CFSE-labeled AC-1 for 2 hours, followed by incubation with Violet-labeled AC-2 for 2 hours and PM collection (n=4 biological replicates).",
    "ncbi_link": "Fmr1: 14265"
  },
  {
    "caption": "RNA lysates from Fmr1+/+ and Fmr1-/- BMDM that were treated with PA (500 µM; 6 hours) were fractionated using a 10%-50% sucrose gradient and separated to polysome, monosome/NTR fractions. The absorbance (260 nm) of RNA was measured and plotted as a function of time (n=3 biological replicates). (B) The ratio of the Abca1, Abcg1, Mertk, Lrp1, Cd36, Cd47 and Rac1 mRNA in polysome to NTR fraction (n=3 biological replicates).",
    "ncbi_link": "Abca1: 11303
Abcg1: 11307
Cd36: 12491
Cd47: 16423
Fmr1: 14265
Lrp1: 16971
Mertk: 17289
Rac1: 19353"
  },
  {
    "caption": "D Fmr1-/- MEF cells were transfected with EV, WT-FMRP or STSA-FMRP plasmids followed by PA treatment (500 µM; 6 hours). Protein lysates were analyzed by western blotting using specific antibodies for ABCA1, MerTK, LRP1, pFMRP, FMRP and β-Actin and fold inductions relative to β-Actin are depicted above the blots (n=5 biological replicates).",
    "ncbi_link": "Fmr1: 14265
FMRP: 14265"
  },
  {
    "caption": "A. Growth curves of the library (black) compared to two different controls under increasing selective pressures. DSB (double-stranded break) Negative Control is a cassette designed to introduce a stop codon at the unrelated gene galK. n=3 for each curve",
    "ncbi_link": "galK: 945358"
  },
  {
    "caption": "B. Growth of the reconstructed LysP T33F mutant compared to wild type cells transformed with a Non-Target gRNA. n=3. C. Growth of the reconstructed LysP Q219I mutant compared to wild type cells transformed with a Non-Target gRNA. n=3",
    "ncbi_link": "LysP: 946667"
  },
  {
    "caption": "D. Absolute quantification of intracellular lysine concentration in wild type and the reconstructed DapF mutants. Quantification was performed using LC-MS, as described in the methods section. n=3. A two-sample student t-test assuming unequal variances was performed to calculate statistical significance. Concentrations are reported as fold-change relative to the wild-type control samples",
    "ncbi_link": "DapF: 948364"
  },
  {
    "caption": "F. Differential gene expression quantified via qPCR for the dapF and lysA genes on a WT, DapF G210D and DapF M260Y backgrounds",
    "ncbi_link": "dapF: 948364
DapF: 948364
lysA: 947313"
  },
  {
    "caption": "C. Absolute quantification of intracellular lysine levels in wild type and the reconstructed LysR S36R mutant. Quantification was performed using LC-MS, as described in the methods section. n=2. Concentrations are reported as fold-change relative to the wild-type control samples",
    "ncbi_link": "LysR: 947311"
  },
  {
    "caption": "F. Absolute quantification of intracellular lysine levels in wild type and the reconstructed ArgP E246 mutant. Quantification was performed using LC-MS, as described in the methods section. n=2. Concentrations are reported as fold-change relative to the wild-type control samples",
    "ncbi_link": "ArgP: 944867"
  },
  {
    "caption": "A Detection of the activation of IRE1α, PERK and ATF6 UPR branches by immunoblotting in control (shCtrl) and Fam20C stable knockdown (shFAM20C) HepG2 cells treated with or without 5 μM Tg for 30 min. ATF6-FL, full-length ATF6; ATF6-N, N-terminal cleavage product of ATF6; Asterisk, unspecific background bands. Fam20C knockdown was verified by protein immunoblotting of Concanavalin A-Sepharose (Con A)-enriched culture medium. Ponceau staining was shown as a loading control.",
    "ncbi_link": "Fam20C: 56975
FAM20C: 56975"
  },
  {
    "caption": "B (Left) Detection of spliced XBP1 (S) and unspliced XBP1 (U) mRNA in shCtrl and shFAM20C HepG2 cells treated with or without 5 μM Tg for 1 h. (Right) Quantification of XBP1 mRNA splicing levels. Data information: data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 (two-tailed Student's t-test).",
    "ncbi_link": "FAM20C: 56975
XBP1: 7494"
  },
  {
    "caption": "C (Left) Detection of XBP1 mRNA splicing in shFAM20C HepG2 cells expressing RNAi-resistant codon-altered Fam20C wild-type (WT) or its inactive D478A mutant (DA) treated with or without 5 μM Tg for 1 h. Fam20C expression levels were shown by protein immunoblotting. (Right) Quantification of XBP1 mRNA splicing levels. Data information: data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 (two-tailed Student's t-test).",
    "ncbi_link": "FAM20C: 56975
Fam20C: 56975
XBP1: 7494"
  },
  {
    "caption": "(Left) Detection of XBP1 mRNA splicing in shCtrl and shFAM20C HepG2 cells (D) treated with or without 2 μg/ml Tm for 8 h. (Right) Quantification of XBP1 mRNA splicing levels. Data information: data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 (two-tailed Student's t-test).",
    "ncbi_link": "FAM20C: 56975
XBP1: 7494"
  },
  {
    "caption": "Detection of XBP1 mRNA splicing in shFAM20C HepG2 cells expressing Fam20C WT or DA (E) treated with or without 2 μg/ml Tm for 8 h. (Right) Quantification of XBP1 mRNA splicing levels. Data information: data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 (two-tailed Student's t-test).",
    "ncbi_link": "FAM20C: 56975
Fam20C: 56975
XBP1: 7494"
  },
  {
    "caption": "G HepG2 cells expressing FLAG-tagged Fam20C were treated with or without 5 μM Tg for 30 min. FLAG-immunoprecipitates were analyzed by PDI immunoblotting.",
    "ncbi_link": "FLAG: 
Fam20C: 56975"
  },
  {
    "caption": "D Phosphorylated PDI catalyzed by Fam20C were analyzed by dual-color immunoblotting with anti-PDI (red) and anti-pS357-PDI (green) antibodies. The yellow signal depicts the phosphorylated PDI species.",
    "ncbi_link": "Fam20C: 56975"
  },
  {
    "caption": "(Left) Detection of p-PDI in WT and PDI KO HepG2 cells (H) treated with 5 μM Tg for indicated times by protein immunoblotting on both regular and phostag gels. (Right) Quantification of p-PDI percentage based on band intensities on phostag gels. Data information: Data were shown as mean ± SEM of three (H) independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 (one-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(Left) Detection of p-PDI in WT and Fam20C KO HeLa cells (I) treated with 5 μM Tg for indicated times by protein immunoblotting on both regular and phostag gels. (Right) Quantification of p-PDI percentage based on band intensities on phostag gels. Data information: Data were shown as mean ± SEM of four (I) independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 (one-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "Fam20C: 56975"
  },
  {
    "caption": "A Fluorescent photomicrographs of HepG2 cells co-transfected with PDI-mEmerald-KDEL (green) and Fam20C-mApple (red). The cells were treated with DMSO (Upper) or 5 μM Tg (Middle) for 30 min. After Tg treatment, the cells were washed with PBS and then returned to culture medium for 60 min (Lower). GM130 was immunostained (blue) as a cis-Golgi marker. Scale bar = 10 μm.",
    "ncbi_link": "KDEL: 
mApple: 
mEmerald: 
PDI: 
Fam20C: 56975"
  },
  {
    "caption": "E Fluorescent photomicrographs of HepG2 cells co-transfected with PDI-mEmerald-KDEL (green) and Fam20C-mApple (red) pretreated with 25 ng/μl CHX for 7.5 h, followed by introduction of DMSO (Upper) or 5 μM Tg (Lower) for 30 min, respectively. GM130 was immunostained (blue) as a cis-Golgi marker. Scale bar = 10 μm.",
    "ncbi_link": "KDEL: 
mApple: 
mEmerald: 
PDI: 
Fam20C: 56975"
  },
  {
    "caption": "F Fluorescent photomicrographs of HepG2 cells co-transfected with PDI-mEmerald-KDEL (green) and Fam20C-mApple-KDEL (red) treated with DMSO (Upper) or 5 μM Tg (Lower) for 30 min, respectively. Scale bar = 10 μm.",
    "ncbi_link": "KDEL: 
mApple: 
mEmerald: 
PDI: 
Fam20C: 56975"
  },
  {
    "caption": "G HepG2 cells were transfected with empty vector (-), FLAG-tagged Fam20C or Fam20C-KDEL followed by introduction without or with 5 μM Tg for 30 min, respectively. PDI phosphorylation was detected by protein immunoblotting on both regular and phostag gels. p-PDI percentage was quantified based on band intensities on phostag gels.",
    "ncbi_link": "FLAG: 
KDEL: 
Fam20C: 56975"
  },
  {
    "caption": "E shCtrl and shFAM20C HepG2 cells were treated without or with 5 μM Tg for 30 min, and in some aliquots of cells Tg was removed for 30 min. Cell lysates were subjected to proteinase K digestion for 3 min and immunoblotting analysis.",
    "ncbi_link": "FAM20C: 56975"
  },
  {
    "caption": "F HepG2 cells expressing HA-tagged PDI and FLAG-tagged Fam20C with different ratios of plasmid concentrations were subjected to proteinase K digestion for 21 min and immunoblotting analysis.",
    "ncbi_link": "FLAG: 
HA: 
PDI: 
Fam20C: 56975"
  },
  {
    "caption": "D Confocal live cell imaging of WT and PDI KO HepG2 cells co-transfected with AgHaloER labeled by P1 (green) and TMR (red) and empty vector (-), PDI WT, S357E or S357A. Scale bar = 10 μm.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "E Confocal live cell imaging of shCtrl and shFAM20C HepG2 cells expressing AgHaloER labeled by P1 (green) and TMR (red). Scale bar = 10 μm.",
    "ncbi_link": "FAM20C: 56975"
  },
  {
    "caption": "F (Upper) Cell viabilities of WT and PDI KO HepG2 cells co-transfected with AgHaloER and empty vector (-), PDI WT, S357E or S357A. Cells were treated by 5 μM Tg for indicated times and visualized by crystal violet staining. (Lower) Quantification of surviving fraction of cells. Data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 versus WT HepG2 (two-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "A (Left) Detection of XBP1 mRNA splicing in WT and PDI KO HepG2 cells treated with or without 5 μM Tg for 1 h. PDI KO was verified by protein immunoblotting. (Right) Quantification of XBP1 mRNA splicing levels. Data were shown as mean ± SEM of three independent experiments. *p < 0.05 (two-tailed Student's t-test).",
    "ncbi_link": "PDI: 5034
XBP1: 22433"
  },
  {
    "caption": "B (Left) Detection of XBP1 mRNA splicing in PDI KO HepG2 cells expressing PDI WT or its mutants treated with or without 5 μM Tg for 1 h. PDI expression levels were shown by protein immunoblotting. (Right) Quantification of XBP1 mRNA splicing levels. Data were shown as mean ± SEM of three independent experiments. *p < 0.05, **p < 0.01 (one-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "PDI: 5034
XBP1: 7494"
  },
  {
    "caption": "C Detection of IRE1α, PERK and ATF6 activation by immunoblotting in PDI KO HepG2 cells expressing PDI S537A or S357E treated with 5 μM Tg for 30 min. Asterisk indicates unspecific background band.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "E HepG2 cells expressing FLAG-tagged IRE1α were treated without or with 5 μM Tg for 1 h. An aliquot of Tg-treated cells was then washed with culture medium and chased for 4 h. FLAG-immunoprecipitates were analyzed by PDI and BiP immunoblotting.",
    "ncbi_link": "FLAG: 
IRE1α: 2081"
  },
  {
    "caption": "F shCtrl and shFAM20C HepG2 cells were treated without or with 5 μM Tg for 1 h. Endogenous IRE1α-immunoprecipitates were analyzed by PDI and BiP immunoblotting.",
    "ncbi_link": "FAM20C: 56975"
  },
  {
    "caption": "G Co-immunoprecipitation of FLAG-tagged IRE1α and HA-tagged PDI in HepG2 cells expressing V5-tagged Fam20C WT or DA.",
    "ncbi_link": "V5: 
Fam20C: 56975"
  },
  {
    "caption": "H Co-immunoprecipitation of FLAG-tagged IRE1α, HA-tagged PDI WT or S357A in HepG2 cells expressing V5-tagged Fam20C.",
    "ncbi_link": "V5: 
Fam20C: 56975"
  },
  {
    "caption": "L Co-immunoprecipitation of FLAG-tagged IRE1α and HA-tagged PDI WT or its binding mutant W128I/L403W in HepG2 cells expressing V5-tagged Fam20C or not.",
    "ncbi_link": "V5: 
Fam20C: 56975"
  },
  {
    "caption": "B Sanger sequencing results of Pdi+/+ (WT) and PdiS359A/S359A (KI) mice.",
    "ncbi_link": "Pdi: 18453"
  },
  {
    "caption": "C (Left) Detection of Xbp1 mRNA splicing in mice liver after injection of Tm (50 ng/g, i.p.) for indicated times. Each lane represents independent animals. (Right) Quantification of Xbp1 mRNA splicing levels at indicated times. Data information: All data were shown as mean ± SEM from five biological replicates. , *p < 0.05, ***p < 0.001 (two-tailed Student's t-test).",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "Detection of Xbp1 mRNA splicing in primary hepatocytes isolated from WT and KI mice treated with 0.2 μM Tg for 2 h (D)",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "Detection of Xbp1 mRNA splicing in primary hepatocytes isolated from WT and KI mice treated with 0.5 μg/ml Tm for 2 h (E).",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "Detection of Bip (F), Pdi (G), Erdj4 (H) mRNA levels by real-time PCR in the liver of the same animals after 24 h of Tm injection. Data information: All data were shown as mean ± SEM from five biological replicates. , *p < 0.05, ***p < 0.001 (two-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "Erdj4: 27362
Bip: 14828
Pdi: 18453"
  },
  {
    "caption": "Detection of Edem1 (I), Il6 (J), Chop (K) mRNA levels by real-time PCR in the liver of the same animals after 24 h of Tm injection. Data information: All data were shown as mean ± SEM from five biological replicates. , *p < 0.05, ***p < 0.001 (two-way ANOVA, the post hoc Tukey's HSD test).",
    "ncbi_link": "Chop: 13198
Edem1: 192193
Il6: 16193"
  },
  {
    "caption": "Cellular locations of native and virally mediated Kcnq1 expression in the cochleaA Diagram showing the major landmarks of the cochlear section to facilitate comparison of data shown in (B-F).B-F Immunolabeling results of Kcnq1 (green) in cochlear cryosections are shown for uninjected WT (B), untreated Kcnq1−/− (C), injected WT (D), and Kcnq1−/− mice given injections into the ST (E) or SM (F). Cell nuclei were outlined by counterstaining with either DAPI (B-D, F) or Qnuclear deep red (E). Scale bars represent approximately 100 μm. Meaning of white arrows are given in the text.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Polarized intracellular trafficking of native and virally expressed Kcnq1 was found specifically in the marginal cellsKcnq1 and cellnuclei were, respectively, labeled green and purple. The SV consists of three layers of cells; marginal cells are the first layer of cells on the side of the endolymphatic space.Cryosection through the SV of WT mice. The large arrow points to the native Kcnq1 (labeled green) in WT mice. Smaller arrows show nuclei of the marginal cells.Cryosection through the SV of a Kcnq1−/−mouse injected with AAV expressing Kcnq1. Labeled in green (bigger arrow) is the AAV1-expressed Kcnq1, found only in the apical membrane of the marginal cells. Smaller arrows show nuclei of the marginal cells. Arrowheads show Kcnq1immunolabeling in fibrocytes outside the SV.Cryosection through the lateral wall of Kcnq1−/−mice showing intracellular distribution of Kcnq1immunolabeling (green) in fibrocytes.Cryosection through the spiral ganglia of cochlea of treated Kcnq1−/−mice showing immunolabeling (green) in the cells of spiral ganglia (arrows).Data information: Purple staining in all panels is counterstaining with DAPI showing the locations of cellnuclei. Scale bars represent appropriately 50 μm.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Quantification of Kcnq1-positive marginal cells and the effect of treatment on the cellular organization of the marginal cells in the SVThe membranes of marginal cells are labeled (red) by phalloidin conjugated with rhodamine.A Immunolabeling results (Kcnq1 labeled in green) in WT mice.B, C Immunolabeling results (Kcnq1 labeled in green) of treated Kcnq1−/−mice, middle (B) and apical (C) turns, respectively.D The percentage of marginal cells having positive Kcnq1immunolabeling signal above a visually detectable level is shown for WT (gray bars, left), untreated Kcnq1−/− (middle), and treated Kcnq1−/−mice (black bars, right). Data are given as mean ± SD (n = 6).E, F The organization of marginal cells in the SV is outlined by labeling with phalloidin conjugated with rhodamine. Results from WT (E) and untreated Kcnq1−/−mice (F) are compared.Data information: Scale bars represent approximately 50 μm.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Comparison of cochlear morphologyA-C Cochlear sections obtained from WT (A), nontreated Kcnq1−/− (B), and treated Kcnq1−/− mice (C) were compared. Major landmarks of the cochlear sections are labeled and pointed by arrows. Scale bars represent approximately 50 μm.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Waveforms of ABRs are compared in WT, untreated Kcnq1−/−, and treated Kcnq1−/− mice, as labeled above data traces. Series of averaged ABR data traces were evoked from tone-burst sounds with intensities ranging from 20 to 90 dB SPL.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Summary of averaged ABR thresholds at various frequencies for different groups of mice; untreated Kcnq1−/− (open triangles), treated Kcnq1−/− (filled triangles), injected WT (filled circles), and uninjected WT (filled squares). Plot legends are given in the figure. The plot with open circles connected with dashed lines represents average data from the five best cases of treated Kcnq1−/− mice. Error bars represent standard error of the mean.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "Click-evoked ABR thresholds of WT (filled squares), treated Kcnq1−/− mice (filled triangles), untreated Kcnq1−/− mice (open squares) measured 4-30 weeks after mice were born. Error bars represent standard error of the mean. Upward arrows indicate that click-ABR thresholds were at the maximal sound level that could be reliably measured by the system.",
    "ncbi_link": "Kcnq1: 16535"
  },
  {
    "caption": "A Differential clustering based on secretagogin (Scgn), neuropeptide, hormone and hormone receptor mRNA expression. Secretagogin‐expressing(+) neurons typically contained corticotropin‐releasing hormone (Crh) and Nr3c1 mRNA transcripts.A1 Clusters of gene transcripts from 130 cells reveal the phenotypic segregation of PVN neurons. Increasing mRNA copy numbers were depicted by a color gradient from deep blue (not detected) to red (high numbers). Secretagogin+ neurons are indicated by red arrows.",
    "ncbi_link": "Crh: 12918
Nr3c1: 14815"
  },
  {
    "caption": "A, A1 siRNA‐mediated secretagogin (scgn) knockdown in cultured hypothalamic neurons, as indicated by reduced secretagogin immunoreactivity (A) and decreased CRH content in the culture medium (A1).",
    "ncbi_link": "scgn: 214189
secretagogin: 214189"
  },
  {
    "caption": "C, C1 siRNA‐mediated in vivo silencing of secretagogin mRNA expression in the PVN provoked somatic CRH accumulation (arrowheads). Scale bar: 150 μm.C2 Quantitative analysis demonstrating significantly increased somatic CRH contents. Note that somatic secretagogin levels remained unchanged, which we interpret as data on a neuronal contingent not affected by siRNA silencing. The lack of secretagogin/CRH co‐localization suggests that secretagogin expression fell below detection threshold in many CRH+ neurons.",
    "ncbi_link": "secretagogin: 214189"
  },
  {
    "caption": "C, D In vivo siRNA‐mediated silencing of secretagogin expression in the PVN occluded the stress‐induced surge of serum ACTH levels (C) and significantly reduced the increase in plasma corticosterone (D). *P 0.05 versus control.",
    "ncbi_link": "secretagogin: 214189"
  },
  {
    "caption": " B-F: Immunoprecipitation (GFP-Trap) experiments between GFP-MOSPD2 (WT and RD/LD mutant) and Flag-tagged STARD3 (B) Approximatively 5 µg of total protein extracts were analyzed by Western blot using anti-Flag (B, C-E) anti-GFP (B-F), and anti-actin (B-F) antibodies. Immunoprecipitated material was analyzed using anti-Flag (B, D-F and anti-GFP (B-F) antibodies",
    "ncbi_link": "MOSPD2: 158747
STARD3: 10948"
  },
  {
    "caption": " B-F: Immunoprecipitation (GFP-Trap) experiments between GFP-MOSPD2 (WT and RD/LD mutant) and Flag-tagge STARD3NL (C) Approximatively 5 µg of total protein extracts were analyzed by Western blot using anti-Flag (B, C-E anti-GFP (B-F), and anti-actin (B-F) antibodies. Immunoprecipitated material was analyzed usin anti-ORP1 (C), and anti-GFP (B-F) antibodies",
    "ncbi_link": "MOSPD2: 158747
STARD3NL: 83930"
  },
  {
    "caption": " B-F: Immunoprecipitation (GFP-Trap) experiments between GFP-MOSPD2 (WT and RD/LD mutant) and Flag-tagge ORP1L (D Approximatively 5 µg of total protein extracts were analyzed by Western blot using anti-Flag (B, C-E), anti-ORP1 (D) ), anti-GFP (B-F), and anti-actin (B-F) antibodies. Immunoprecipitated material was analyzed using anti-Flag (B, D-F ), and anti-GFP (B-F) antibodies",
    "ncbi_link": "MOSPD2: 158747
ORP1L: 114876"
  },
  {
    "caption": " B-F: Immunoprecipitation (GFP-Trap) experiments between GFP-MOSPD2 (WT and RD/LD mutant) and Flag-tagge STARD11 (E Approximatively 5 µg of total protein extracts were analyzed by Western blot using anti-Flag (B, C-E anti-GFP (B-F), and anti-actin (B-F) antibodies Immunoprecipitated material was analyzed using anti-Flag (B, D-F and anti-GFP (B-F) antibodies",
    "ncbi_link": "STARD11: 10087
MOSPD2: 158747"
  },
  {
    "caption": " B-F: Immunoprecipitation (GFP-Trap) experiments between GFP-MOSPD2 (WT and RD/LD mutant) an HA-tagged PTPIP51 (F) (WT and FFAT-deficient). Approximatively 5 µg of total protein extracts were analyzed by Western blot usin anti-HA (F) anti-GFP (B-F), and anti-actin (B-F) antibodies. Immunoprecipitated material was analyzed using anti-Flag (B, D-F ), and anti-GFP (B-F) antibodies",
    "ncbi_link": "MOSPD2: 158747
PTPIP51: 55177"
  },
  {
    "caption": " G: Immunoprecipitation (anti-Flag) experiment between Flag-tagged STARD3NL (WT and FFAT-deficient) and endogenous MOSPD2. Proteins extracts and immunoprecipitated material were analyzed by Western blot using anti-MOSPD2, anti-STARD3NL and anti-actin antibodies ",
    "ncbi_link": "STARD3NL: 83930"
  },
  {
    "caption": " B: Western blot analysis of MOSPD2 and VAP proteins in control HeLa cells (WT) and in HeLa cells expressing a control shRNA (shCtrl) and two individual shRNAs targeting MOSPD2 (shMOSPD2-α or shMOSPD2-β). Quantification of MOSPD2 protein level is shown below. Means and error bars (SD) are shown. n: three independent experiments ",
    "ncbi_link": "MOSPD2: 158747"
  },
  {
    "caption": " C: Endogenous MOSPD2 (green) was labelled in control HeLa cells (WT), in cells expressing a control shRNA (shCtrl), and in cells expressing two individual shRNAs targeting MOSPD2 (shMOSPD2-α or shMOSPD2-β). Scale bar: 10 µm ",
    "ncbi_link": "MOSPD2: 158747"
  },
  {
    "caption": " E-F: Endogenous MOSPD2 (green) staining in HeLa cells expressing Flag-STARD3NL (E (anti-Flag; magenta) Data information: (A, D-F): The subpanels on the right are higher magnification (3.5x) images of the area outlined in white. The Overlay panel shows merged green and magenta images. The Coloc panel displays a colocalization mask on which pixels where the green and the magenta channels co-localize are shown in white. Right: Linescan analyses with fluorescence intensities of the green and magenta channels along the white arrow shown on the subpanel Overlay. Black rectangles indicate the positions of late endosomes (E). Scale bars: 10 µm ",
    "ncbi_link": "STARD3NL: 83930"
  },
  {
    "caption": " E-F: Endogenous MOSPD2 (green) staining in HeLa cells expressin Flag-STARD3NL ∆FFAT (F) (anti-Flag; magenta) Data information: (A, D-F): The subpanels on the right are higher magnification (3.5x) images of the area outlined in white. The Overlay panel shows merged green and magenta images. The Coloc panel displays a colocalization mask on which pixels where the green and the magenta channels co-localize are shown in white. Right: Linescan analyses with fluorescence intensities of the green and magenta channels along the white arrow shown on the subpanel Overlay Scale bars: 10 µm",
    "ncbi_link": "STARD3NL: 83930"
  },
  {
    "caption": " G: Pearson correlation coefficients between endogenous MOSPD2 and Flag-STARD3NL (WT or ΔFFAT) staining are shown. Each dot represents a single cell (number of cells: MOSPD2-Flag-STARD3NL: 27; MOSPD2-Flag-STARD3NL ΔFFAT: 26; from three independent experiments). Means and error bars (SD) are shown. Mann-Whitney test (two-tailed P value; ****: P< 0,0001) ",
    "ncbi_link": "STARD3NL: 83930"
  },
  {
    "caption": " A: Western blot analysis of MOSPD2, VAP-A and VAP-B proteins in control HeLa cells (WT) and in HeLa cells transfected with a control siRNA (siCtrl), and with siRNA targeting MOSPD2 (siMOSPD2), VAP-A and VAP-B (siVAP-A/VAP-B), and MOSPD2, VAP-A and VAP-B (siMOSPD2/VAP-A/VAP-B) ",
    "ncbi_link": "MOSPD2: 158747
VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": " B-F: TEM images o MOSPD2 (D: siMOSPD2 -silenced HeLa cells. An interpretation scheme representing contacts between organelles is shown on the right; the ER, endosomes and ILV are in dark, light and medium gray, respectively. Mitochondria and Golgi are in pink and light green, respectively. Scale bars: 500 µm ",
    "ncbi_link": "MOSPD2: 158747"
  },
  {
    "caption": " B-F: TEM images o VAP-A and VAP-B (E: siVAP-A/VAP-B -silenced HeLa cells. An interpretation scheme representing contacts between organelles is shown on the right; the ER, endosomes and ILV are in dark, light and medium gray, respectively. Mitochondria and Golgi are in pink and light green, respectively. Scale bars: 500 µm ",
    "ncbi_link": "VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": " B-F: TEM images o MOSPD2, VAP-A and VAP-B (F: siVAP-A/VAP-B/MOSPD2) -silenced HeLa cells. An interpretation scheme representing contacts between organelles is shown on the right; the ER, endosomes and ILV are in dark, light and medium gray, respectively. Mitochondria and Golgi are in pink and light green, respectively. Scale bars: 500 µm ",
    "ncbi_link": "MOSPD2: 158747
VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": " G-I: Quantification by stereology of ER-mitochondria (G contacts. The percentages of mitochondria perimeter in contact with the ER (G are shown as means and error bars (SEM). (G) 200 (HeLa), 208 (siCtrl), 199 (siMOSPD2), 202 (siVAP-A/VAP-B), 199 (siMOSPD2/VAP-A/VAP-B) mitochondria from 8, 10, 8, 12 and 12 cells, respectively, were analyzed",
    "ncbi_link": "MOSPD2: 158747
VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": " G-I: Quantification by stereology o ER-endosome (H contacts The percentages o ), endosome perimeter in contact with the ER (H are shown as means and error bars (SEM) (H, I) 202 (HeLa), 189 (siCtrl), 148 (siMOSPD2), 141 (siVAP-A/VAP-B), 221 (siMOSPD2/VAP-A/VAP-B) endosomes from 9, 19, 10, 14 and 12 cells, respectively, were analyzed. Kruskal-Wallis with Dunn\"s multiple comparison test (*: P-values <0.05; ***: P< 0,001; ****: P <0.0001)",
    "ncbi_link": "MOSPD2: 158747
VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": " G-I: Quantification by stereology o endosome-endosome (I) contacts. The percentages o endosome perimeter in contact with an endosome (I) are shown as means and error bars (SEM) (H, I) 202 (HeLa), 189 (siCtrl), 148 (siMOSPD2), 141 (siVAP-A/VAP-B), 221 (siMOSPD2/VAP-A/VAP-B) endosomes from 9, 19, 10, 14 and 12 cells, respectively, were analyzed. Kruskal-Wallis with Dunn\"s multiple comparison test (*: P-values <0.05; ***: P< 0,001; ****: P <0.0001)",
    "ncbi_link": "MOSPD2: 158747
VAP-A: 9218
VAP-B: 9217"
  },
  {
    "caption": "A. Representative H&E staining and immunohistochemical analysis of the androgen receptor (AR) in the dorsolateral prostate (DLP) of PtenL2/L2 and Pten(i)pe-/- mice, sham-operated (sham) or castrated (CTX) at 3 months after gene inactivation (AGI), and analyzed at 1 month after surgery. Scale bars: 100 µm. N=3 mice per condition.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "F. Violin plots depicting transcript levels of androgen-responsive genes in luminal-C cells of sham and CTX Pten(i)pe-/- mice. P-values were determined by Wilcoxon rank sum test.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "H. Violin plots depicting the transcript levels of inflammation-related genes in luminal-C cells of sham and CTX Pten(i)pe-/- mice. P-values were determined by Wilcoxon rank sum test.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "J, K. Violin plots depicting the transcript levels of hypoxia-related genes (J) and plasticity-related genes (K) in luminal-C cells of sham and CTX Pten(i)pe-/- mice. P-values were determined by Wilcoxon rank sum test.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "C. Gland areas in DLP of sham and CTX control and Pten/Hif1a(i)pe-/- mice. Five glands per mouse were quantified. N=3 mice/condition.",
    "ncbi_link": "Hif1a: 15251
Pten: 19211"
  },
  {
    "caption": "G. Representative immunohistochemical detection of cleaved caspase 3 (CC3) in DLP of Pten(i)pe-/- and Pten/Hif1a(i)pe-/- mice, sham or CTX at 3 months AGI, and analyzed 1 or 1, 2, 3 and 30 days after surgery, respectively. N=3 mice/condition.",
    "ncbi_link": "Hif1a: 15251
Pten: 19211"
  },
  {
    "caption": "I. Western blot analysis of CC3 in protein lysates of organoids generated from prostates of Pten(i)pe-/- and Pten/Hif1a(i)pe-/- mice at 3 months AGI, and treated with enzalutamide (Enz) for 24 hours at the indicated concentrations. β-actin was used as a loading control.",
    "ncbi_link": "Hif1a: 15251
Pten: 19211"
  },
  {
    "caption": "B. Representative H&E staining of DLP of Pten/Hif1a(i)pe-/- mice sham and CTX at 3 months AGI and analyzed at 5 months after surgery. N=4-5 mice/condition. C. Gland areas in DLP of control and Pten/Hif1a(i)pe-/- mice, sham and CTX at 3 months AGI and analyzed at 5 months after surgery. N=3-4 mice/condition. Five glands per mouse were quantified. Data presented are mean, and error bars correspond to SEM.",
    "ncbi_link": "Hif1a: 15251
Pten: 19211"
  },
  {
    "caption": "E. Representative immunohistochemical detection of AR and TROP2 in DLP of Pten/Hif1a(i)pe-/- mice, sham and CTX at 3 months AGI and analyzed at 5 months after surgery. N = 3-4 mice/condition.",
    "ncbi_link": "Hif1a: 15251
Pten: 19211"
  },
  {
    "caption": "F. Representative H&E staining of DLP of sham and CTX Pten(i)pe-/- mice, treated with vehicle or PX-478, as depicted in (E). Scale bar: 100 µm. N=3-4 mice/condition.",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "H. Gland areas of DLP of sham and CTX Pten(i)pe-/- mice, treated with vehicle or PX-478, as depicted in (E). N=3-4 mice/condition. Data presented are mean ± SEM. Five glands per mouse were quantified,",
    "ncbi_link": "Pten: 19211"
  },
  {
    "caption": "E Immunohistochemistry for SOX9 (brown) in control (Sox9fl/fl;RosaCre-) or Sox9-null (Sox9fl/fl;RosaCre+) mice following fibrosis. Bile ducts (bd) and hepatocytes (arrowheads) indicated. SOX9 is absent, even in bile ducts in Sox9-null liver. Size bar, 25 μm (A, B and E), 10 μm (C).",
    "ncbi_link": "RosaCre: 2777477
Sox9: 20682"
  },
  {
    "caption": " A-J Representative images and quantification shown for olive oil treated (n=6) or chronic CCl4 (n=5 Sox9fl/fl;RosaCreER-; n=8 Sox9fl/fl;RosaCreER+) induced fibrosis or following sham operation (n=5) or BDL (n=7 Sox9fl/fl;RosaCreER-; n=5 Sox9fl/fl;RosaCreER+)) induced fibrosis. A Picrosirius red (PSR) staining (collagen deposition in red) counterstained with fast green (top row) and immunohistochemistry for α-SMA (brown staining bottom row; activated HSC / myofibroblast marker) in olive oil treated (left) or chronic CCl4 induced fibrosis (right) in control and Sox9-null mice. Size bar = 200 μm. ",
    "ncbi_link": "RosaCreER: 2777477
Sox9: 20682"
  },
  {
    "caption": "B, C Quantification of surface area covered by the PSR staining or α-SMA in control (Cnt) and Sox9-null (Null) in (A).",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "D PSR staining (red; top row) and immunohistochemistry for α-SMA (brown; middle row) and CK19 (brown; bottom row) in control and Sox9-null mice following sham operation (left) or BDL induced fibrosis (right). Size bar = 500 μm.",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "G, H Liver function is improved in Sox9-null mice following CCl4 (G) or BDL (H) induced fibrosis compared to control mice. Reduction in serum alanine aminotransferase (ALT; G, H) and bilirubin (H) down to levels shown in non-fibrotic mice (olive oil treated groups; Oil).",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "G, H Liver function is improved in Sox9-null mice following CCl4 (G) or BDL (H) induced fibrosis compared to control mice. Reduction in serum alanine aminotransferase (ALT; G, H) and bilirubin (H) down to levels shown in non-fibrotic mice (olive oil treated groups; Oil).",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "I Sox9-loss improved severity of fibrosis compared to control mice indicated by quantification of bridging fibrosis in PSR sections following CCl4. Olive oil treated mice had no bridging fibrosis, in line with a non-fibrotic liver histology in (A).",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "J Ductal hyperplasia as quantified by the surface area covered by CK19 positive ducts in (D) is reduced in Sox9-null mice compared to control following BDL. All mice were treated with tamoxifen (Tam) which did not induce ectopic expression of SOX9 in non-fibrotic livers (Figure 2A, E and Appendix Figure S3). All experiments are n≥5 as indicated. Two-tailed unpaired t-test was used for statistical analysis. Data in bar charts show means ± s.e.m. P values indicated.",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "A-C Representative images shown for olive oil treated (n=5) or chronic CCl4 (n=5) induced fibrosis or following sham operation (n=6 Sox9fl/fl;AlbCre-; n=5 Sox9fl/fl;AlbCre+) or BDL (n=5 Sox9fl/fl;AlbCre-; n=8 Sox9fl/fl;AlbCre+) induced fibrosis. SOX9 immunohistochemistry (brown; A), in situ hybridization for Sox9 (brown) and α-Sma (red) and collagen deposition by PSR staining (red; B) in control (Sox9fl/fl;AlbCre-) or Sox9-null (Sox9fl/fl;AlbCre+) mice following fibrosis. Higher magnified image of SOX9 localization in discrete cells within the scar is shown for CCl4 and BDL in the Sox9fl/fl;AlbCre+ mice (A).",
    "ncbi_link": "AlbCre: 2777477
Sox9: 20682"
  },
  {
    "caption": " A-C Representative images shown for olive oil treated (n=5) or chronic CCl4 (n=5) induced fibrosis or following sham operation (n=6 Sox9fl/fl;AlbCre-; n=5 Sox9fl/fl;AlbCre+) or BDL (n=5 Sox9fl/fl;AlbCre-; n=8 Sox9fl/fl;AlbCre+) induced fibrosis. SOX9 immunohistochemistry (brown; A), in situ hybridization for Sox9 (brown) and α-Sma (red) and collagen deposition by PSR staining (red; B) in control (Sox9fl/fl;AlbCre-) or Sox9-null (Sox9fl/fl;AlbCre+) mice following fibrosis. Higher magnified image of SOX9 localization in discrete cells within the scar is shown for CCl4 and BDL in the Sox9fl/fl;AlbCre+ mice (A). ",
    "ncbi_link": "α-Sma: 
AlbCre: 2777477
Sox9: 20682"
  },
  {
    "caption": "A-C Representative images shown for olive oil treated (n=5) or chronic CCl4 (n=5) induced fibrosis or following sham operation (n=6 Sox9fl/fl;AlbCre-; n=5 Sox9fl/fl;AlbCre+) or BDL (n=5 Sox9fl/fl;AlbCre-; n=8 Sox9fl/fl;AlbCre+) induced fibrosis. SOX9 immunohistochemistry (brown; A), in situ hybridization for Sox9 (brown) and α-Sma (red) and collagen deposition by PSR staining (red; B) in control (Sox9fl/fl;AlbCre-) or Sox9-null (Sox9fl/fl;AlbCre+) mice following fibrosis. Higher magnified image of SOX9 localization in discrete cells within the scar is shown for CCl4 and BDL in the Sox9fl/fl;AlbCre+ mice (A).",
    "ncbi_link": "AlbCre: 2777477
Sox9: 20682"
  },
  {
    "caption": "F Expression of SOX9 protein by immunohistochemistry in quiescent (Q) and activated (A) HSCs extracted from Sox9fl/fl;AlbCre+ mice.",
    "ncbi_link": "AlbCre: 2777477
Sox9: 20682"
  },
  {
    "caption": "G Individual fluorescent channels showing localization and expression of α-SMA (left panel), SOX9 (middle panel) and composite image for α-SMA (green) and SOX9 (red) in right panel in activated Sox9fl/fl;AlbCre+ HSCs (genotyping shown in Appendix Figure S9). Two-tailed unpaired t-test was used for statistical analysis. Data in bar charts show means ± s.e.m. Size bars = 100 μm (A), 10 μm (B) 200 μm (C), 25 μm (G).",
    "ncbi_link": "AlbCre: 
Sox9: 20682"
  },
  {
    "caption": "A, B Flow cytometry of CD45+CD11B+ cells in control (Sox9fl/fl;RosaCre-; A) and Sox9-null (Sox9fl/fl;RosaCre+; B) livers stained for Ly6C and MHCII (far left) to identify four populations of cells with differences in their expression of MerTK, CD64, F4/80 and MHCII.",
    "ncbi_link": "RosaCre: 2777477
Sox9: 20682"
  },
  {
    "caption": "D, E Graphical representation of cell numbers in the four Ly6C and MHCII cell populations in control and Sox9-null livers. Data are representative of four independent experiments.",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "F F4/80 immunohistochemistry (brown staining) in control and Sox9-null mice livers following 4-weeks CCl4 induced fibrosis. Size bar = 100μm. Two-tailed unpaired t-test was used for statistical analysis. Data in bar charts show means ± s.e.m. P values indicated. All experiments are n=4.",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "(B) qRT-PCR analysis using primers overlapping exons 15 and 16 permitted to quantify the non‐skipped α1S form: 18±6% (**P⩽0.001, n=19) and 10±7% (**P⩽0.001 n=19) (black bars) of the total α1S mRNA (grey bars) at 2 and 6 months post injection in TA of AAV1‐(U7‐ESE) and AAV1‐(U7‐SA):ΔDHPR or AAV1‐(U7‐Ctrl): c as a control, respectively.",
    "ncbi_link": "DHPR: 12292
α1S: 12292"
  },
  {
    "caption": "(C) Six months post injection, lysates from TAΔDHPR (ΔDHPR) and TACtrl (c) were immuno‐blotted for α1S or α-actin for four mice. Graph depicts mean±s.e.m. of relative expression of α1S subunit determined by densitrometry and nomalized to the α-actin expression for each muscle. Results were expressed in protein levels of α1S subunit in TAΔDHPR normalized to TACtrl for each mice, **P⩽0.001, n=4.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(D) Longitudinal cryo‐sections from TAΔDHPR (ΔDHPR) and TACtrl (c) were stained with anti‐α1S subunit (red) and anti‐laminin (green) antibodies, nuclei were visualized by Dapi (blue) and imaged by confocal microscopy. Bars represent 20 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(B) The internal diameters (shortest diameter) from all fibres throughout the total muscle section were recorded and analysed. Muscles from five different animals were examined. The bar graph presents mean±s.e.m. of the number of myofibres by fibre diameter class for TAΔDHPR (black) and TACtrl(grey).",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(C) Transversal sections of TAΔDHPR (ΔDHPR) and TACtrl (c) were stained with haematoxylin and eosin, bars represent 100 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(D) To quantify fibrosis, transversal sections of total muscle were stained with Red Sirius and quantified using Histolab Software (marked in blue), data were normalized with total surface of each muscle (orange line surrounding the sections), bars represent 500 μm. (E) Quantification is presented in bar graph and showed 4.1±0.1 fold increase of fibrosis in TAΔDHPR (ΔDHPR) compared to TACtrl (c) (**P0.001, n=4).",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(A) mRNA from TAΔDHPR and TACtrl tissues were extracted and nNOS expression was quantified by qRT-PCR. Results are expressed as mean±s.e.m., **P0.001, n=4.",
    "ncbi_link": "DHPR: 12292
nNOS: 18125"
  },
  {
    "caption": "(B) Transversal cryo‐sections of TAΔDHPR (ΔDHPR) and TACtrl (c) were stained with anti‐nNOS (red), anti‐laminin (green) antibodies, nuclei with Dapi (blue) and imaged by confocal microscopy. Bars represent 20 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(D) Longitudinal cryo‐sections of TAΔDHPR (ΔDHPR) and TACtrl (c) were stained with anti‐FoxO3a (red), anti‐laminin (green) antibodies, nuclei with Dapi (blue) and imaged by confocal microscopy. Bars represent 20 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(E) mRNA from TAΔDHPR and TACtrl tissues were extracted and regulation of autophagy genes expression was followed by qRT-PCR. Bnip3, CathepsinL, LC3 and PI3KIII expression (noted in red) were significantly increased in TAΔDHPR compared with the controlateral TACtrl, **P0.001, n=4.",
    "ncbi_link": "Bnip3: 12176
DHPR: 12292
CathepsinL: 13039
LC3: 67443///66734
PI3KIII: 30955"
  },
  {
    "caption": "(B) Transversal cryo‐sections were stained with anti‐LC3b (red), anti‐dystrophin (green) antibodies, nuclei with Dapi (blue) and imaged by confocal microscopy. Upper panel: TACtrl (Ctrl) and lower panel: TAΔDHPR (ΔDHPR). Bars represent 20 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(C) Myofibres isolated from control (Ctrl) or 6 months post‐injected FDB (ΔDHPR) muscles were processed for immuno‐fluorescent labelling for P62 (green) and LC3b (red) and imaged by confocal microscopy. Scale bars, 10 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(A) Ultrathin sections of TAΔDHPR (ΔDHPR) and TACtrl (c) were imaged by electron microscopy. Cis, terminal cisternae; T, tubule; SR, sarcoplasmic reticulum. Bars: 500 nm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(B) Myofibres isolated from Ctrl or ΔDHPR FDB muscles 6 months post injection were processed for immuno‐fluorescent labelling for RyR1 (green), SERCA (red), Dapi (blue) and imaged by confocal microscopy. Scale bars, 10 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(A) Lysates from TAΔDHPR (ΔDHPR) and TACtrl (c) were immuno‐blotted for RyR1 or α‐actin. (n=4). Graph depicts mean±s.e.m. of relative expression of RyR1 determined by densitometry and nomalized to the α‐actin expression for each muscle. Results were expressed in protein levels of ΔDHPR in TAΔDHPR normalized to TACtrl for each mice, *P⩽0.005, n=4.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(B) Longitudinal cryo‐sections of TAΔDHPR (ΔDHPR) and TACtrl (c) were stained with anti‐α1S subunit (red), anti‐RyR1 (green) antibodies and imaged by confocal microscopy. Bars=20 μm.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "Localization of α 1S subunit. Whole skeletal muscle fibres enzymatically isolated from Ctrl (A-D) or ΔDHPR (E-H) FDB muscles 6 months post injection were processed for immuno‐fluorescent labelling for α1 S subunit (red) and laminin (green). Scale bars, 10 μm; Arrows indicate α1 S subunit expression on sarcolemma; antibody labelling was visualized by serial confocal microscopy and represented as movies of the optical sections (Supplementary Movies S5A and S5B). (D, H) Present projections of confocal Z‐series (step between each frame is 1 μm) along XZ and YZ planes as indicated.",
    "ncbi_link": "DHPR: 12292"
  },
  {
    "caption": "(b) Cells stably expressing WT or D620N GFP-VPS35 or otherwise transiently transfected with a panel of GFP-VPS35 constructs were lysed and the respective GFP-tagged protein recovered by immunoprecipitation (IP).",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(c) Untransfected HeLa cells or cells stably expressing VPS29-GFP, GFP-VPS35 wild-type or GFP-VPS35 D620N were lysed and the lysates incubated with anti-VPS26 to IP the retromer CSC.",
    "ncbi_link": "VPS29: 51699
VPS35: 55737"
  },
  {
    "caption": "(d) Cells stably expressing the VPS29-GFP V90D mutant that cannot assemble with VPS35 were transiently transfected with mCherry-tagged WT VPS35, D620N and H675R constructs, along with an additional control of mCherry-FAM21 tail. Cells were lysed 48 h post transfection, and VPS29-GFP V90D and associated proteins were recovered by anti-GFP native IP. Blots shown are representative of experiments replicated at least twice.",
    "ncbi_link": "FAM21: 387680
V90D: 51699
VPS29: 51699
VPS35: 55737"
  },
  {
    "caption": "a) Cells expressing either WT GFP-VPS35 or the D620N mutant were treated with siRNA to abolish expression of endogenous VPS35. Each dish of cells was lysed in either HEPES lysis buffer (H) or PBS lysis buffer (P). Following centrifugation, equal portions of each lysate were combined to generate a mixed lysate (H/P). Each lysate was incubated with anti-GFP to recover the respective GFP-tagged VPS35 protein.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(b) Similar to (a), but only cells expressing GFP-VPS35 wild type were analysed, either mock treated or treated with siRNA to silence FKBP15 expression.",
    "ncbi_link": "FKBP15: 23307
VPS35: 55737"
  },
  {
    "caption": "(c) Cells stably expressing WT or D620N GFP-VPS35 were treated with indicated siRNAs, lysed and immunoprecipitated as in (a).",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(a,b) Cells expressing either WT or D620N GFP-VPS35 were treated with siRNA to silence expression of endogenous VPS35, fixed and labelled for GFP and FKBP15 (a) or FAM21 (b). Cells were imaged by fluorescence microscopy. Scale bar, 20 μm.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(c) Cells stably expressing WT or D620N GFP-tagged VPS35 were treated with siRNA to abolish expression of endogenous VPS35 and subsequently fixed and labelled for GFP and either VPS26, FKBP15 or FAM21. The cells were imaged using Cellomics automated fluorescence microscopy. Approximately 250 cells per well in four wells were analysed for each cell line. The data for FKBP15 and FAM21 spot intensity were normalized to GFP-VPS35 and VPS26 signals. P0.0002 for both FKBP15 and FAM21 spot intensity in D620N compared with WT. Error bars indicate s.d.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(d) Cells stably expressing either WT GFP-VPS35 or the D620N mutant were treated with siRNA to silence the expression of endogenous VPS35. Cells were permeabilized by flash freezing followed by rapid thawing and centrifuged to separate supernatant (S) and membrane pellet (P) fractions.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(e) The graph shows the percentage of membrane-associated FKBP15 and strumpellin and is the mean of three experiments. The error bars indicate s.e.m. A representative blot of three experiments is shown, indicating the efficacy of the knockdown of endogenous VPS35 and also further showing that membrane proteins such as the CIMPR are detected only in the pellet fraction.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "a) HeLa cells stably expressing GFP-VPS35 WT and D620N were treated with bafilomycin A1 or DMSO vehicle control. Endogenous LC3-II and tubulin levels were examined by western blot. A representative experiment of six experiments is shown. (b) Quantification of the representative experiment in triplicate shown in a, in which endogenous LC3-II levels are normalized to tubulin and expressed as a ratio of levels in WT. ***P=7.86 × 10−6 (DMSO) and 3.81 × 10−5 (Baf) by 2-tailed Student's t-test.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "c) HeLa cells stably expressing GFP-VPS35 WT and D620N were transfected with mRFP-LC3. The number of LC3 vesicles was quantified by Cellomics automated fluorescence microscopy. A representative experiment of three independent experiments is shown, with 344 (WT) and 401 (D620N) cells analysed. ***P0.0001 by 2-tailed Student's t-test.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(d) GFP-VPS35 WT and D620N-expressing cells were transfected with HA-Q74 and immunostained for HA. The percentage of transfected cells with aggregates was counted by a blinded experimenter. The quantification shows the mean of three experiments in triplicate with minimum 200 cells per replicate. ***P=0.00086 by 1-tailed Student's t-test.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(f) Cells stably expressing WT and D620N GFP-VPS35 were transfected with GFP-α-synuclein A53T and GFP for 48 h and analyzed by western blotting.",
    "ncbi_link": "α-synuclein: 6622
VPS35: 55737"
  },
  {
    "caption": "(h) VPS35 was knocked down with two individual siRNA nucleotides in HeLa cells, and cells were treated with bafilomycin A1 and lysed as in a. A representative experiment is shown in triplicate",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(j) Protein levels of CSC, including VPS35, VPS26 and VPS29), were assessed upon VPS35 knockdown, confirming previous results that knockdown of one component destabilizes the CSC. All error bars indicate s.e.m.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(a) HeLa cells were transfected with pEGFP vector or GFP-FAM21 tail for 48 h and subsequently treated with bafilomycin A1 as in Fig. 4. Endogenous LC3-II and tubulin levels were assessed by western blot. (b) Quantification of the representative experiment in triplicate shown in a, of two independent experiments. *P=0.02 (DMSO) and 0.08 (Baf) by 2-tailed Student's t-test.",
    "ncbi_link": "FAM21: 387680"
  },
  {
    "caption": "(c) HeLa cells stably expressing GFP-VPS35 WT and D620N were transfected with pEGFP vector or GFP-FAM21, and subsequently treated with bafilomycin A1, lysed and subjected to western blot as in a. (d) Quantification of the representative experiment in triplicate shown in c, of two independent experiments. **P=0.008 by 2-tailed Student's t-test.",
    "ncbi_link": "FAM21: 387680
VPS35: 55737"
  },
  {
    "caption": "(e) Cells were depleted of WASH1, treated with bafilomycin A1 and examined for endogenous LC3-II, tubulin, WASH1 and GAPDH levels. A representative experiment of six independent experiments is shown. (f) Quantification of the representative experiment shown in e. **P=0.002 (DMSO) and P=0.0028 (Baf) by 2-tailed Student's t-test.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "g) HeLa cells depleted of WASH1 by siRNA were transfected with GFP-LC3 for 24 h. The number of LC3 vesicles was quantified by Cellomics automated fluorescence microscopy. A representative experiment of two independent experiments is shown, with 757 (control) and 695 (knockdown) cells analysed. ***P0.0001 by 2-tailed Student's t-test.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "(h) HeLa cells depleted of FKBP15 were transfected with GFP-LC3 and vesicles were quantified as in g. A representative experiment of two independent experiments in triplicate is shown, with 579 (control) and 815 (knockdown) cells analysed in total.",
    "ncbi_link": "FKBP15: 23307"
  },
  {
    "caption": "(i) HeLa cells depleted of FKBP15 were subsequently transfected with a GFP-Q74 construct for 24 h and fixed in PFA. The percentage of transfected cells with aggregates was counted by a blinded experimenter. The quantification shows the mean of two experiments, each in triplicate with min 220 cells counted per replicate",
    "ncbi_link": "FKBP15: 23307"
  },
  {
    "caption": "(j) FKBP15 was depleted in HeLa cells as in e. A representative blot from three independent experiments in triplicate is shown. Error bars indicate s.e.m.",
    "ncbi_link": "FKBP15: 23307"
  },
  {
    "caption": "(a) HeLa cells were immunostained for endogenous ATG9A and VPS35 and subjected to confocal microscopy. Magnified areas are shown on the right of the pictures. (b) HeLa cells were transfected with ATG9A-GFP for 24 h, and subsequently fixed, immunostained for endogenous WASH1 and subjected to confocal microscopy. (c) HeLa cells were transfected with ATG9A-GFP as in b, but immunostained instead for endogenous FAM21.",
    "ncbi_link": "ATG9A: 79065"
  },
  {
    "caption": "(d) HeLa cells stably expressing GFP-VPS35 WT and D620N were depleted of endogenous VPS35 using 40 nM of siRNA, and subsequently immunostained for TGN46 and endogenous ATG9A and subjected to confocal microscopy. (e) Colocalization between TGN and ATG9A is expressed in terms of the Pearson's Coefficient. n=25 cells (WT) and 33 cells (D620N). Error bars represent s.e.m. and **P=0.01 by 2-tailed Student's t-test. Scale bars in (a-d), 10 μm.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "(a) HeLa cells depleted of WASH1 with two successive siRNA treatments were either starved in Hank's balanced salt solution for 1 h or kept in full medium. Following fixation, cells were immunostained for TGN46, ATG9A and VPS35 and subjected to confocal microscopy. Representative pictures with magnified areas are shown. Scale bar, 10 μm. (b) Colocalization between TGN and ATG9A is expressed in terms of the Pearson's coefficient. Number of cells analysed: 38 (control basal), 46 (knockdown basal), 36 (control starved), 53 (knockdown starved). Error bars represent s.e.m. and ***P=0.0005 (basal) and P=0.0004 (starved) by 2-tailed Student's t-test.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "(a) HeLa cells stably expressing GFP-VPS35 WT and D620N were transfected with mRFP-LC3 for 24 h, immunostained for endogenous ATG9A, and imaged by confocal microscopy.",
    "ncbi_link": "LC3: 440738///81631///84557
VPS35: 55737"
  },
  {
    "caption": "(c) HeLa cells depleted of WASH1 were transfected with GFP-LC3 for 24 h, immunostained for endogenous ATG9A, and imaged by confocal microscopy.",
    "ncbi_link": "LC3: 440738///81631///84557
WASH1: 100287171"
  },
  {
    "caption": "(a) SH-SY5Y cells were depleted of WASH1, treated with bafilomycin A1 and examined for LC3-II, tubulin, WASH1 and GAPDH levels. Blots shown are representative of two independent experiments in triplicate. (b) Quantification of the representative experiment in triplicate shown in (a), of two independent experiments. Error bars indicate s.e.m. **P=0.0058 by 1-tailed Student's t-test.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "(c) WASH1-depleted SH-SY5Y cells were trypsinized, stained with propidium iodide and analysed by flow cytometry. Living cells, not stained with propidium iodide, are shown as a percentage of total cells. The graph depicts a representative experiment in triplicate out of two independent experiments, in which at least 10,000 cells were analysed in each replicate. Error bars indicate s.e.m. *P=0.045 by 1-tailed Student's t-test.",
    "ncbi_link": "WASH1: 100287171"
  },
  {
    "caption": "Same as (E) with amiRhen1-14 scions and non-transgenic WT or hen1-14 rootstocks. Average relative U6-normalized band-intensity quantifications from two biological replicates are indicated.",
    "ncbi_link": "hen1: 827839
U6: 28719273"
  },
  {
    "caption": "Phenotype of pSUC2::amiRSUL plants in hst-1/-25/-26 backgrounds.",
    "ncbi_link": "SUL: 827580
hst: 819666
SUC2: 838877"
  },
  {
    "caption": "RT-qPCR analysis of SUL mRNA levels in leaves with the indicated genotypes. Error-bars: SD. Welch's t-test p-values are indicated. n=5.",
    "ncbi_link": "SUL: 827580"
  },
  {
    "caption": "amiRSUL northern analysis in input and AGO1-immunoprecipitated (AGO1-IP) fractions isolated from leaves of pSUC2::amiRSUL plants in the specified genotypes. No Ab: No antibody added to the HST input extract (IP negative control). miR165/166 and U6 were probed as endogenous controls. AGO1 western analysis and Coomassie blue (Coom.) staining of the western blot membrane are provided as controls. amiRSUL band-intensity quantifications, U6-normalized for input samples, are indicated.",
    "ncbi_link": "SUL: 827580
HST: 819666
miR165: 3770111///3766638
SUC2: 838877
U6: 28719273"
  },
  {
    "caption": "amiRSUL northern analysis, in biological duplicates, in scions (S) and rootstocks (R) in the specified genotypes' grafting combinations (amiR: pSUC2::amiRSUL) (see also Appendix Fig.S12B). U6: as in (A). Average relative U6-normalized band-intensity quantifications are indicated for each tissue.",
    "ncbi_link": "SUL: 827580
SUC2: 838877
U6: 28719273"
  },
  {
    "caption": "amiRSUL northern analysis, in biological duplicates, from total RNA extracted from aphids fed on WT or amiR plants, in the specified genetic backgrounds. U6: as in (A). Average relative U6-normalized band-intensity quantifications are indicated.",
    "ncbi_link": "SUL: 827580
U6: 28719273"
  },
  {
    "caption": "Localization of HST:GFP and, as a reference, of tmGFP9 expressed under the pSUC2 promoter in Arabidopsis primary leaves (C) or roots (D). CW: calcofluor white staining. Scale bars: 20 µm.",
    "ncbi_link": "SUC2: 838877"
  },
  {
    "caption": "Confocal fluorescence images of the differentiation and division zones of Arabidopsis root tips expressing pSUC2::HST:GFP, pSUC2::GFP or pSUC2::tmGFP9. Scale bars: 100 µm. Confocal fluorescence images of the differentiation and division zones of pSUC2::GFPhst-1 or pSUC2::tmGFP9hst-1 root tips. Scale bars: 100 µm.",
    "ncbi_link": "GFP: 
GFP9: 
HST: 819666
hst-1: 819666
SUC2: 838877"
  },
  {
    "caption": "Subcellular localizations of HST:GFP expressed from the UBQ10 promoter (pUBQ) in Arabidopsis roots (i). Distinct planes of the same root cells imaged by confocal microscopy are shown (ii-iii). PI: propidium iodide staining. Scale bars: 50µm (i); 10µm (ii-iii).",
    "ncbi_link": "UBQ: 825880
UBQ10: 825880"
  },
  {
    "caption": "Subcellular localizations of hst-3:GFP expressed from pUBQ in root cells. Distinct planes of the same root cells imaged by confocal microscopy are shown (i-ii). PI: as in (A). Scale bars: 10µm.",
    "ncbi_link": "UBQ: 825880"
  },
  {
    "caption": "miR395 northern analysis in scions (S) and hyl1-2 rootstocks (R), in the indicated genotypes' combinations, under SO4-sufficient (+SO4) or SO4-starved (-SO4) conditions, in two biological replicates (rep.). U6 was probed as an endogenous control. Relative U6-normalized band-intensity quantifications are indicated for each tissue in -SO4 conditions.",
    "ncbi_link": "miR395: 
hyl1: 837498
U6: 28719273"
  },
  {
    "caption": "miR160 northern analysis in Meselect-separated leaf vasculature and epidermis in WT versus hst-1 plants, in three biological replicates (rep.). U6: as in (A). Relative U6-normalized band-intensity quantifications are indicated.",
    "ncbi_link": "miR160: 
hst-1: 819666
U6: 28719273"
  },
  {
    "caption": "Basic fuchsin staining of protoxylem (unfilled arrowheads) and metaxylem (filled arrowheads) in WT, shr-2 or hst-1 roots. *: protoxylem gap. Scale bars: 10 µm.",
    "ncbi_link": "hst-1: 819666
shr: 829919"
  },
  {
    "caption": "(A) Ability of DONSON   deletions to support replisome  assembly. The DONSON   depletion experiment, as that in Figure 2B, was performed using 3×FLAG-tagged versions of the full length (amino acid residues 1-579) or N-terminal/C-terminal deletions (amino acid residues 1-157, 133-579, 1-476, 1-369) of Xenopus (x) DONSON, whose final concentrations were about 0.06 μM. The signals derived from DONSON  are indicated with dotted lines. His-p27  and His-geminin  were used as negative controls. Asterisk (*), non-specific bands. (B) Interaction  of DONSON  with the replication factors. 3×FLAG-tagged full length (xF), N-terminal region residue 1-157 (xN), middle region residue 133-369 (xM), and C-terminal region residue 358-579 (xC) versions of Xenopus DONSON   were added to an interphase egg  extract at about 8.8 μM. After incubation for 15 min, the whole extract was subjected to a  pull-down assay using FLAG-M2 beads, and the precipitated proteins were analyzed by immunoblotting  (FLAG-IP). The extracts (2.5%) were analyzed for comparison (Input).",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "(G). GFP-tagged ERMES complex proteins retain their characteristic punctate structure in Δlam6, suggesting that Lam6 is not an essential complex member. Scale bar represents 5 μm.",
    "ncbi_link": "lam6: 850761
Lam6: 850761"
  },
  {
    "caption": "(A) Fluorescence microscopy demonstrates that the overexpression of Cherry-Lam6 (OE-Cherry-LAM6) results in an expansion of the following three contact sites: ERMES (Mdm34-GFP), NVJ (Nvj1-GFP), and vCLAMP (GFP-Vps39). This suggests that an increase in Lam6 levels in the contact site is sufficient for its expansion. The numbers represent the average contact site size (120 cells per sample). Scale bar represents 5 μm.",
    "ncbi_link": "Lam6: 850761"
  },
  {
    "caption": "(B) Immuno-EM verified that GFP-Lam6 overexpression indeed causes an expansion of contact site size. While vCLAMP was hardly visible in WT cells, it could be detected easily in the OE strain (albeit often had ER tubules invading it). The NVJ underwent expansion as well as evoked PMN in OE strains, and the ER-mitochondria contact became large and elongated instead of small and distinct. N, nucleus; M, mitochondria; V, vacuole. Scale bar represents 200 nm (see also Figure S3I).",
    "ncbi_link": "Lam6: 850761"
  },
  {
    "caption": "(A) Fluorescent microscopy shows that the ERMES contact (as measured by the number of Mdm34-GFP puncta per cell) expanded in the Δvps39 background relative to WT. However, the expansion did not occur on the background of Δvps39 Δlam6, demonstrating that Lam6 is necessary for ERMES expansion under these conditions. Scale bar represents 5 μm.(B) Quantitation of (A). Bars represent the percentage of cells containing the specific number of puncta/cell out of total cells counted for the strain (for WT, n = 234 cells; for Δvps39, n = 246; for Δvps39 Δlam6, n = 271).",
    "ncbi_link": "lam6: 850761
Lam6: 850761
vps39: 851482"
  },
  {
    "caption": "(C) Fluorescent microscopy demonstrates that downregulating ERMES contacts (by growing GALp-MDM34 strains in glucose) indeed caused expansion of vCLAMP (GFP-Vps39). However, this expansion was diminished in a Δlam6 background. Scale bar represents 5 μm (see also Figure S4).",
    "ncbi_link": "GALp: 
lam6: 850761
MDM34: 852654"
  },
  {
    "caption": "Dose-response curves representing 72-h viability measurements for six selected BRAFV600E melanoma cell lines after treatment with vemurafenib. Ranges of estimated IC50 and Emax for the selected lines are shown. Data are represented as mean ± SD.",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "D c-Jun expression in WM115 cells transfected with JUN siRNA relative to no RNA and non-targeting controls quantified in triplicate 48 h after transfection.",
    "ncbi_link": "JUN: 3725"
  },
  {
    "caption": "E, F Apoptosis in WM115 cells with or without 48 h JUN knockdown after 96-h treatment with increasing doses of vemurafenib",
    "ncbi_link": "JUN: 3725"
  },
  {
    "caption": "E, F Apoptosis in WM115 cells with or without 48 h JUN knockdown after 96-h treatment with increasing doses of selumetinib (F)",
    "ncbi_link": "JUN: 3725"
  },
  {
    "caption": "Fraction of c-JunHighcells (as measured by single-cell (immunofluorescence microscopy) after 48 h JUN knockdown followed by 24-h treatment with vemurafenib. Fold changes are shown relative to control-treated cells. Data are presented as mean ± SD.",
    "ncbi_link": "JUN: 3725"
  },
  {
    "caption": "Single-cell pS6(Ser235/236) levels in the c-JunHigh and c-JunLow fractions of cells (as measured by single-cell multiplex immunofluorescence microscopy) after 48 h of JUN knockdown and 24-h treatment with 0.32 μM vemurafenib. Single-cell pS6 data are presented as box-and-whisker plots with median signal intensities and interquartile ranges; bars extending to 1.5× the interquartile range are shown for each condition as a measure of variance. P-values were calculated using a two-sided nonparametric Mann-Whitney U-test.",
    "ncbi_link": "JUN: 3725"
  },
  {
    "caption": "Back skin sections of K15CrePR+/T; Wls∆/∆ and Control K15CrePR+/+; Wlsflox/flox mice treated with mifepristone from P7 during 12 weeks (P90), immunostained for LYVE1 (red), and counterstained with DAPI (blue). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice. Scale bar, 100 μm. epi, epidermis; der, dermis.",
    "ncbi_link": "Cre: 2777477
K15: 16665
Wls: 68151"
  },
  {
    "caption": "Images of intravital microscopy analyses showing aligned HF rows in the back skin interconnected by LV in the Prox1CreERT2; Rosa-LSL-eYPF mice. Dotted boxes denote HF triads; White arrowheads denote capillaries stemming from HF triads interconnecting to other HF triads in adjacent rows. n= 3 - 4 mice. Scale bar, 50 μm.",
    "ncbi_link": "eYPF: 
Cre: 2777477
ERT2: 2099
Rosa: 14910
Prox1: 19130"
  },
  {
    "caption": "Back skin sections of Controls and K14ΔNβ-cateninER+/T mice immunostained for LYVE1 (red), and counterstained with DAPI (blue). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice. Scale bar, 50 μm. epi, epidermis; der, dermis.",
    "ncbi_link": "Nβ-catenin: 12387
K14: 16664"
  },
  {
    "caption": "Histogram of the LV caliber in skin sections from Controls and K14ΔNβ-cateninER+/T mice. n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.",
    "ncbi_link": "Nβ-catenin: 12387
K14: 16664"
  },
  {
    "caption": "Histograms of RNA ISH analyses by RNAscope to quantify the level of expression of ITGA5 (D), DCN (E), PKD1 (F) and PLXND1 (G), assessed by the number of mRNA spots present in LYVE1+ cells in the vicinity of HF in P55 and P70 mouse back skin. n= average of 30 LYVE1+ cells / sample, n= 3 mice.",
    "ncbi_link": "DCN: 13179
ITGA5: 16402
PKD1: 18763
PLXND1: 67784"
  },
  {
    "caption": "H&E staining (A) and histogram of the HF length (B) in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice injected with vehicles (Control), Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with CSA and vehicle (CSA); and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI treated with tamoxifen, CSA and intradermal Diphtheria Toxin (CSA+DT) starting from early Telogen (P49) and analyzed at the end of the treatments (P58). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.",
    "ncbi_link": "iDTR: 
Cre: 2777477
ERT2: 2099
ROSA26: 14910
Prox1: 19130"
  },
  {
    "caption": "Ki67 immunostaining (C) and histogram of the number of Ki67+ cells per HF (D) in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice injected with vehicles (Control), Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with CSA and vehicle; and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI treated with tamoxifen, CSA and intradermal DT, starting from early Telogen (P49) and analyzed at the end of the treatments (P58). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.",
    "ncbi_link": "iDTR: 
Cre: 2777477
ERT2: 2099
ROSA26: 14910
Prox1: 19130"
  },
  {
    "caption": "LYVE1 immunostaining (E) and histogram of the LV caliber (F) analyzed in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice injected with vehicles (Control), Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with CSA and vehicle (CSA); and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with tamoxifen, CSA and intradermal DT, starting from early Telogen (P49) and analyzed at the end of the treatments (P58). Scale bar, 10 μm. n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.",
    "ncbi_link": "iDTR: 
Cre: 2777477
ERT2: 2099
ROSA26: 14910
Prox1: 19130"
  },
  {
    "caption": "H&E staining (G) and histogram of the HF length (H) in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice (Control), and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with tamoxifen and intradermal DT, starting from Anagen (P30) and analyzed at the end of the treatments (P37). n= 3 - 4 skin samples per mouse, n= 3 - 4 mice. Scale bar, 200 μm. Data represent the mean value ± SEM.",
    "ncbi_link": "iDTR: 
Cre: 2777477
ERT2: 2099
ROSA26: 14910
Prox1: 19130"
  },
  {
    "caption": "Cleaved caspase 3 immunostaining (I) and histogram of the number of cleaved caspase 3+ cells per HF (J) in adult back skin sections from Prox1CreERT2+/+; LSL-ROSA26-iDTRKI/KI mice (Control), and Prox1CreERT2+/T; LSL-ROSA26-iDTRKI/KI mice treated with tamoxifen and intradermal DT, starting from Anagen (P30) and analyzed at the end of the treatments (P37). Scale bar, 50 μm. n= 3 - 4 skin samples per mouse, n= 3 - 4 mice.",
    "ncbi_link": "iDTR: 
Cre: 2777477
ERT2: 2099
ROSA26: 14910
Prox1: 19130"
  },
  {
    "caption": " E) HEK293 cells stably expressing LPL-V5 or PL-V5 were transfected with NC siRNA or siRNA against TRX. Lipase and TRX levels were tested as for Fig 1A ",
    "ncbi_link": "TRX: 7295"
  },
  {
    "caption": " F) Txnip overexpression in HEK293 cells stably expressing LPL-V5 or PL-V5 hinders LPL, but not PL, secretion ",
    "ncbi_link": "Txnip: 10628"
  },
  {
    "caption": " B). A Western blot of a non-reducing gel of the lysate and pellet fraction of LPL grown in cells lacking LMF1 (HEK293∆LMF1), normal HEK293 cells or cells with additional LMF1 (+LMF1). LPL monomers and aggregates are marked as above ",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": " C). Co-translational LPL folding was carried out in the presence of SP HEK293 or HEK293∆LMF1 cells. At the indicated time points, AMS was added to reactions to differentiate reduced (R) and oxidized (O) LPL. The position of the stacker layer is indicated ",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": " G and H). Data from (D-F) was combined to show the trends in LPL folding over time for reactions using HEK293 or HEK293∆LMF1 cells. Each point is the average of three independent experiments, and error bars represent the standard deviation ",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": "Differential sensitivity of HEK293 cells containing and lacking LMF1 (A) to drugs that perturb cellular redox homeostasis. Cells were treated with BSO, DTT, or tunicamycin as described in materials and methods. Treated cell and untreated cells were counted, and the fraction of surviving cells was calculated. Three wells were counted and averaged for each data point, and three independent trials were carried out per condition. Significance was determined by a 2-tailed student's t-test.",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": " C). The redox sensor ERroGFP-S4 shows that HEK293∆LMF1 cells have a more oxidized ER than HEK293 and HEK293+LMF1 cells both untreated and when stressed by expression of LPL-mCherry. A two-tailed student's t-test was used to calculate the significance of the difference in the ratio of oxidized/reduced GFP fluorescence intensity between cell types. Each data point is one of three spots measured per cell, 17 cells were measured per condition. Significance was determined by a 2-tailed student's t-test ",
    "ncbi_link": "mCherry: 
LMF1: 64788
LPL: 4023"
  },
  {
    "caption": "). Secretion of LPL-V5 from HEK293∆LMF1 cells transiently transfected with LMF1 bearing the indicated cysteine to alanine mutations. Lipase levels in the lysate and pellet, and LMF1 levels in the pellet (α-HIS), are also probed. GAPDH serves as a loading control.",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": "α-His Western blot to detect acid trapped partners of LMF1. Samples were TCA precipitated, treated with NEM, and LMF1 was purified via its C-terminal His tag. Samples were resolved by reducing or nonreducing SDS-PAGE. The lanes marked -LMF1 are HEK293∆LMF1 cells included as a negative control.",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": "Samples were TCA precipitated, treated with NEM, and LMF1 was purified via its C-terminal His tag. Samples were resolved by reducing or nonreducing SDS-PAGE. The lanes marked -LMF1 are HEK293∆LMF1 cells included as a negative control. Samples were probed with an antibody for TRX.",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": "Bottom, center and top slices from a z-stack of a cld/wt or cld/cld MEF cell. YPet-tagged fibronectin is in green and mCherry-Sec61β, an ER marker, is in red. Note fibronectin assembly into the extracellular matrix in cld/wt cells. cld/wt cells had significantly higher amounts of fibronectin outside of the ER than cld/cld cells by a two-tailed student's t-test.",
    "ncbi_link": "mCherry: 
YPet: 
fibronectin: 2335
Sec61β: 10952"
  },
  {
    "caption": "Bottom, center and top slices show that LDLR is retained in the ER in cells HEK293∆LMF1 cells. LDLR-GFP is in green and mCherry-Sec61β is in red. Note the clumping of LDLR in the ER in HEK293∆LMF1 cells. The ratio of LDLR within the ER/total LDLR was significantly higher for HEK293∆LMF1 cells than HEK293 or HEK293+LMF1 cells by a 2-tailed student's t-test.",
    "ncbi_link": "LMF1: 64788"
  },
  {
    "caption": "B Heatmap of the anti-proliferative activity of ALK inhibitors across Ba/F3 cell lines with different ALK mutations.",
    "ncbi_link": "ALK: 11682"
  },
  {
    "caption": "(A) Cells were transfected with scrambled (SCR) or anti-LC3 (LC3) siRNAs, and 48 h later infected with PV at an MOI of 50 pfu/cell, or mock infected. Cells were collected at 6 h.p.i., and immunoblots were performed on lysates for p62, GAPDH, and LC3.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) Triplicate plates of H1-Hela cells were infected with PV at an MOI of 0.1 pfu/cell, virus RNA and host GAPDH RNA were measured by qRT-PCR. Virus RNA levels were normalized to GAPDH levels using the delta-Ct method. NH4Cl treatment was as described in Figure 4, and Guanidine HCl (2 mM) was added to the media at the time of infection. The data shown are pooled from three replicate experiments, and the titer of cell-associated virus collected at 6h.p.i. from each replicate was determined by plaque assay.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(B) Dot plot indicating fraction of tf-Reporters delivered to the lysosome by ATG7-independent mechanisms. The median red:green ratio of each population was used to calculate fractional delivery according to the following formula: (ratiosgATG7-ratiosgATG9A)/(ratioNegativeCtl1-ratiosgATG9A), with the assumption that sgATG9A yields a true autophagy-null phenotype. Mean values for each reporter are indicated by a black bar. n=3 for each reporter.",
    "ncbi_link": "ATG7: 10533
ATG9A: 79065"
  },
  {
    "caption": "(C) Wild-type (WT) K562 cells and indicated deletion isolates were treated with 100 nM Bafilomycin A1 (BafA1) or DMSO for 18h and analyzed by flow cytometry for red:green ratio of tf-NBR1. Median values for each sample are identified by a black line within each violin. The red dotted line across all samples corresponds to the red:green ratio in wild-type cells. The red solid line across all samples corresponds to the ratio observed under maximally inhibited conditions (ATG9AKO cells). n = 10,000 cells.",
    "ncbi_link": "ATG9A: 79065"
  },
  {
    "caption": "(E) Correlative light and electron microscopy (CLEM) of K562 ATG7KO cells expressing tf-NBR1 under basal conditions. Analysis workflow is indicated by green arrows. White arrows indicate representative structures of interest. White boxes demarcate zoomed areas in subsequent images. NBR1, green; Hoechst, blue. Scale bar (small images), 2.5 µm. Scale bar (large images), 250 nm.",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(B) Gene correlation plot of average beta scores for lipidation dependent autophagy (tf-NDP52, from (Shoemaker et al, 2019)) and lipidation independent autophagy (average of tf-NBR1 from ATG7KO, ATG10 KO and ATG3 KO cells Highlighted in red are genes with a beta score > 0.5 across all three lipidation-deficient cell lines. In black are lipidation components. Dashed lines, top 1% of beta scores.",
    "ncbi_link": "ATG10: 83734
ATG3: 64422
ATG7: 10533"
  },
  {
    "caption": "(C) Wild-type K562 cells and indicated deletion isolates expressing Cas9 and tf-NDP52 or tf-NBR1 were transduced with individual sgRNAs for indicated genes. The median red:green ratio of each population was used to calculate the fold-repression according to the following formula: (ratiosgGene-ratiosgATG9A)/(ratioNegativeCtl-ratiosgATG9A), with the assumption that sgATG9A yields a true autophagy-null phenotype. Deeper shades of red indicate stronger suppressor phenotypes. Genes were clustered on the basis of their patterns of genetic interactions.",
    "ncbi_link": "ATG9A: 79065
Cas9: 57852564"
  },
  {
    "caption": "(B) Representative confocal micrograph (as maximum intensity projections) of ATG7KO/TAX1BP1KO K562 cells expressing tf-NBR1. Selected region (white box) of micrograph is shown as single and merged channels from fluorescence microscopy. RFP, magenta; GFP, green; merged, white; Hoechst, blue. Scale bars: large panel, 5 µm; small panels, 1 µm.",
    "ncbi_link": "ATG7: 10533
TAX1BP1: 8887"
  },
  {
    "caption": "(C) Correlative light and electron microscopy (CLEM) of K562 ATG7KO/TAX1BP1KO cells expressing tf-NBR1 under basal conditions. Analysis workflow is indicated by green arrows. White arrow indicates a structure of interest. White box demarcates zoomed area in bottom images. NBR1, green; Hoechst, blue.",
    "ncbi_link": "ATG7: 10533
TAX1BP1: 8887"
  },
  {
    "caption": "(A) Wild-type and indicated K562 knock-out cells expressing tf-NBR1 were transfected with TagBFP or TagBFP-RavZ, and BFP-positive cells were analyzed for red:green ratio by flow cytometry. The median red:green ratio of each sample was used to calculate flux relative to WT+TagBFP. Bar graphs represent mean +/- SD from three independent experiments. n > 7,500 cells per sample.",
    "ncbi_link": "BFP: 
RavZ: 57035674"
  },
  {
    "caption": "(B) K562-derived extracts prepared from wild-type (WT) and clonal deletion isolates were resolved by SDS-PAGE followed by immunoblotting (IB) with indicated antibodies. All samples were normalized by total protein using a BCA assay prior to loading. Bar graphs represent mean +/- SD from independent experiments (n=4 {NBR1, NDP52}; n=3 {SQSTM1}). p values for WT vs ATG9AKO was determined using a one sample test (theoretical mean = 1) with Bonferroni correction.",
    "ncbi_link": "ATG9A: 79065"
  },
  {
    "caption": "(A) Extracts derived from wild-type and deletion K562 cells expressing tf-NBR1 were normalized for total protein by BCA. NBR1 was immunoprecipitated using GFP-Trap dynabeads. Input and eluate were resolved by SDS-PAGE followed by immunoblotting (IB) with indicated antibodies.",
    "ncbi_link": "NBR1: 4077"
  },
  {
    "caption": "(B) Representative confocal micrographs (as maximum intensity projections) of wild-type K562 and ATG9AKO cells expressing tf-NBR1. Selected regions (white box) of micrographs are shown as single and merged channels from fluorescence and immunofluorescence microscopy against indicated proteins. In conditions where puncta were not observed, representative cytoplasmic regions were selected to showcase diffuseness of signal. TAX1BP1, SQSTM1, or NDP52, magenta; NBR1, green; Hoechst, blue.",
    "ncbi_link": "ATG9A: 79065"
  },
  {
    "caption": "(C) Shown are representative confocal micrographs (as maximum intensity projections) of K562 cells expressing tf-NDP52 (or tf-TAX1BP1) and transduced with sgRNAs targeting ATG9A (sgATG9A) or a negative control (sgControl). Selected regions (white box) of micrographs are shown as single and merged channels from fluorescence microscopy. RFP, magenta; GFP, green; Hoechst, blue.",
    "ncbi_link": "ATG9A: 79065"
  },
  {
    "caption": "(C) HEK293T cells were transfected with either myc-TAX1BP1WT or myc-NBR1WT and indicated TagBFP-V5-TAX1BP1 variants. Extracts derived from transfected cells were immunoprecipitated (IP) with anti-TagBFP magnetic beads. Input and eluates were resolved by SDS-PAGE followed by immunoblotting (IB) with indicated antibodies.",
    "ncbi_link": "BFP: 
myc: 
V5: 
NBR1: 4077
TAX1BP1: 8887"
  },
  {
    "caption": "(D) HEK293T cells were transfected with myc-NBR1WT and indicated TagBFP-V5-TAX1BP1 variants. Extracts derived from transfected cells were immunoprecipitated (IP) with anti-TagBFP magnetic beads. Input and eluates were resolved by SDS-PAGE followed by immunoblotting (IB) with indicated antibodies.",
    "ncbi_link": "BFP: 
myc: 
V5: 
NBR1: 4077
TAX1BP1: 8887"
  },
  {
    "caption": "(C) Representative confocal micrographs (as maximum intensity projections) from wild-type, TAX1BP1KO, and ATG7KO/TAX1BP1KO K562 cells expressing tf-NBR1 and transduced with indicated sgRNA. Selected regions (white box) of micrographs are shown as single and merged channels from fluorescence and immunofluorescence microscopy against indicated proteins. FIP200, magenta; NBR1, green; Hoechst, blue. (D) Quantitation of colocalization between NBR1 with FIP200 in wild-type, TAX1BP1KO, and ATG7KO/TAX1BP1KO cells imaged in (C) Bar graphs represent mean +/- SD for three independently generated deletion cell lines (dots). sgATG9A samples were compared using a one-way ANOVA (p < 0.0001) with Tukey HSD post-test. ***, p < 0.001. n > 200 NBR1 puncta for each biological replicate. (E) Quantitation of FIP200 intensity at NBR1 puncta in wild-type, TAX1BP1KO, and ATG7KO/TAX1BP1KO cells imaged in (C). Bar graphs represent mean +/- SD for three independently generated deletion cell lines (dots). n > 80 FIP200-positive puncta for each biological replicate. Samples were compared using a one-way ANOVA (p < 0.0001) with Tukey HSD post-test. ***, p < 0.001. a.u., arbitrary intensity units.",
    "ncbi_link": "ATG7: 10533
ATG9A: 79065
TAX1BP1: 8887"
  },
  {
    "caption": "(M) Death rates in TNF-treated cell lines including clonal RelA-knockout population (mean of three independent experiments ± standard deviation).",
    "ncbi_link": "RelA: 19697
TNF: 21926"
  },
  {
    "caption": "(A) TNF-induced mRNA expression in indicated L929 cell lines measured via qRT-PCR (mean of three independent experiments ± standard deviation, two-tailed Student's t-test *P<0.05, **P<0.01).",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(I,J) (I) TNF-induced distributions of death times (representative data of three independent experiments), and (J) death rates obtained by live-cell microscopy (mean of three independent experiments ± standard deviation).",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(G,H) (G) Distribution of death times (representative data of three independent experiments), or (H) death rates in TNF-treated wt, parental A20 KO cells, or A20 KO cells reconstituted with an NFκB-inducible transgene (fIL8-A20; mean of three independent experiments ± standard deviation).",
    "ncbi_link": "IL8: 20309
NFκB: 18033
TNF: 21926
A20: 21929"
  },
  {
    "caption": "(J) experimental measurements of 24-hour fractional survival after varying durations of transient or sustained (24h) TNF stimulation (mean of three independent experiments ± standard deviation; two-tailed Student's t-test ***P<0.001, or no statistically significant difference, n.s., P>0.05).",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "(H) Death rates in TNF-treated indicated cell lines including isogenic IκBα/IκBε-knockout population (mean of three independent experiments ± standard deviation).",
    "ncbi_link": "IκBα: 18035
IκBε: 18037
TNF: 21926"
  },
  {
    "caption": "(I) Death rates in TNF-treated cell lines treated with targeting (siA20) or non-targeting (siCon) siRNA (mean of three independent experiments ± standard deviation).",
    "ncbi_link": "TNF: 21926
A20: 21929"
  },
  {
    "caption": "A. Four full-thickness excisional wounds were produced on each of CD18-/- or WT mice by 6 mm biopsy punches. Each wound received intradermal injection of 2.5x105 AT-MSCs or PBS control. Each wound region was digitally photographed at the indicated time points, and wound areas were analyzed using Adobe Photoshop. Depicted are representative macroscopic pictures of PBS injected or AT-MSCs injected WT or CD18-/- wounds at days 0, 3, 5, 7 and 9 post-wounding. B. Quantitative analysis of 20 wound areas per group, expressed as percentage of the initial wound size at day 0. The line in each group represents the mean value of 20 wounds from 5 mice. *p<0.05, **p<0.01, ***p<0.001 by Student's t-test with Welch's correction. ",
    "ncbi_link": "CD18: 16414"
  },
  {
    "caption": "A. AT-MSCs or PBS were intradermally injected to WT or CD18-/- wounds and the wound tissues were harvested at days 2, 5, 7 post-wounding. Depicted are representative photographs of wound cryosections at days 2 and 5 post-wounding stained for human-specific β2M (green). Nuclei were stained with DAPI (blue). Scale bars: 100 µm.",
    "ncbi_link": "CD18: 16414"
  },
  {
    "caption": "D. The expression of human TGF-β1 in cultured AT-MSCs and wound tissues of WT or CD18-/- wounds received AT-MSCs injection was quantified by qPCR with primers specifically amplify human TGF-β1, and normalized on the numbers of MSCs in each condition Data are expressed as mean ± SEM, n = 8 wounds (2 wounds x 4 mice) per time point",
    "ncbi_link": "CD18: 16414
TGF-β1: 7040"
  },
  {
    "caption": "A. Cryosections of PBS or AT-MSCs injected CD18-/- wounds at days 5 and 7 post-wounding were immunostained for α-SMA (red). Nuclei were stained with DAPI (blue). The dashed lines separate epidermis and wound bed. e, epidermis; wb, wound bed. Scale bars: 100 µm. B. Quantification of α-SMA immunofluorescence shown in (A) ",
    "ncbi_link": "CD18: 16414"
  },
  {
    "caption": "C. Cryosections of AT-MSCs injected CD18-/- wounds at day 5 post-wounding were co-immunostained for human β2M (green) and TGF-β1 (red, upper panel) or α-SMA (red, lower panel).",
    "ncbi_link": "CD18: 16414"
  },
  {
    "caption": "A-F. Representative photographs of immunofluorescent staining for α-SMA (red) and human β2M (green) on cultured human AT-MSCs (A), murine primary dermal fibroblasts (mFB) (B), mFB treated with 2 ng/ml recombinant human TGF-β1 (C), and co-cultures of mFB with AT-MSCs (D) or TGF-β1 siRNA transfected AT-MSCs (E) or control siRNA transfected AT-MSCs (F) after 48 h culture. Nuclei were counterstained with DAPI (blue). G. Quantification of α-SMA immunofluorescence shown in (A-F)",
    "ncbi_link": "TGF-β1: 7040"
  },
  {
    "caption": "H. Four full-thickness excisional wounds were produced on each of CD18-/- mouse by 6 mm biopsy punches. Each wound received intradermal injection of 2.5x105 AT-MSCs or human dermal fibroblasts (HDF) or TGF-β1 siRNA transfected AT-MSCs or control siRNA transfected AT-MSCs or PBS. Each wound region was digitally photographed at days 0, 3, 5, 7 and 10 post-wounding, and wound areas were analyzed using Adobe Photoshop. The depicted result is the quantitative analysis of all wound areas per group, expressed as percentage of the initial wound size at day 0.",
    "ncbi_link": "CD18: 16414
TGF-β1: 7040"
  },
  {
    "caption": "A-C. 2.5x105 of TGF-β1 siRNA or control siRNA transfected AT-MSCs were intradermally injected around each of CD18-/- murine wound. PBS mock injection served as negative control. Wound tissue were harvested at day 2, 5, and 7 post-wounding for quantification of human TGF-β1 mRNA (A) at day 2 by qPCR, total TGF-β1 (B) and active TGF-β1 (C) protein at day 5 by ELISA.",
    "ncbi_link": "CD18: 16414
TGF-β1: 7040"
  },
  {
    "caption": "D. From total RNA, the mature miR-21 and endogenous control RNU6B were converted to cDNA, and quantified by qPCR based TaqMan microRNA assays. The expression of miR-21 was normalized on RNU6B. Data is given as mean ± SEM of three independent experiments.",
    "ncbi_link": "RNU6B: 
miR-21: 406991"
  },
  {
    "caption": "A. AT-MSCs were pretreated with a TGFβRI inhibitor SB431542 at 10 µM, or control DMSO for 1 h, and subsequently exposed to r.h. TGF-β1 at indicated concentrations. The cells were cultured for another 24 h and harvested for miR-21 assay. The expression of miR-21 was normalized on RNU6B. Data is given as mean ± SEM of three independent experiments.",
    "ncbi_link": "RNU6B: 
miR-21: 406991"
  },
  {
    "caption": "B-D. AT-MSCs were transfected with 30 nM Smad7-siRNAs or control siRNA. Untransfected AT-MSCs served as control. RNA and protein were isolated 2 days after transfection for Smad7 expression by qPCR (B) and western blot (C). The remaining cells were treated with r.h. TGF-β1 at indicated concentrations for another 24 h. The expression of human TGF-β1 was analyzed by qPCR and normalized on human GAPDH (D). Data is given as mean ± SEM of three independent experiments.",
    "ncbi_link": "GAPDH: 
Smad7: 4092
TGF-β1: 7040"
  },
  {
    "caption": "E-G. AT-MSCs were transfected with 5 nM miR-21 mimic or control mimic, and were exposed to r.h. TGF-β1 2 days after transfection at indicated concentrations for another 24 h. The expression miR-21 was analyzed by qPCR-based miR-21 assay normalized on RNU6B (E), Samd7 protein level was shown by western blot (F), and human TGF-β1 expression was monitored by qPCR normalized on human GAPDH (G). Data is given as mean ± SEM of three independent experiments.",
    "ncbi_link": "GAPDH: 
RNU6B: 
miR-21: 406991
TGF-β1: 7040"
  },
  {
    "caption": "H-J. AT-MSCs were transfected with 50 nM miR-21 inhibitor or control inhibitor, and were exposed to r.h. TGF-β1 2 days after transfection at indicated concentrations for another 24 h, and subsequently subjected to the analysis of expression of miR-21 (H), Smad7 protein (I) and human TGF-β1 mRNA (J). Data is given as mean ± SEM of three independent experiments.",
    "ncbi_link": "miR-21: 406991
TGF-β1: 7040"
  },
  {
    "caption": "K-L. Full-thickness excisional wounds were produced on CD18-/- mice by 6 mm biopsy punches. One day after wounding, each wound received intradermal injection of 2.5x105 AT-MSCs that had been transfected with 50 nM miR-21 inhibitor or control inhibitor 2 days after transfection. CD18-/- wounds received mock injection with PBS served as control. Each wound region was digitally photographed at days 0, 3, and 6 post-wounding, and expressed as percentage of the initial wound size at day 0 (K). Wound tissues were harvested on day 6 post-wounding for quantification of total TGF-β1 protein by ELISA (L). Data is given as mean ± SEM; n = 5 wounds per group; *, p<0.05; **, p<0.01, by one-way ANOVA with Tukey's test. MSC_miR-21-IN, miR-21 inhibitor transfected AT-MSCs; MSC_ctrl-IN, control inhibitor transfected AT-MSCs.",
    "ncbi_link": "CD18: 16414
miR-21: 406991"
  },
  {
    "caption": "B, Heat-map displaying the expression of bromodomain genes in metastases from patients with cutaneous malignant melanoma (n=367). BRD4, SMARCA4, TRIM28 and BRPF1 are highlighted by a black bar. Gene expression is represented by z-score.",
    "ncbi_link": "BRD4: 23476
BRPF1: 7862
SMARCA4: 6597
TRIM28: 10155"
  },
  {
    "caption": "C, Kaplan-Meier analysis of overall survival of patients with stage III melanoma in cluster C1 (median survival 79.5 months) and C2 (median survival 25.9 months), and of patients with stage III melanoma with high (median survival 61.5 months) or low (median survival 107 months) TRIM28 expression. The log-rank test was used for statistical testing of survival data.",
    "ncbi_link": "TRIM28: 10155"
  },
  {
    "caption": "C, GSEA plot of RAS signature genes in in TRIM28high and TRIM28low metastatic tumors (n=367), and in A375 cells transduced with shT28-1, shT28-2 or shNTC (shLUC and shSCR) (n=3 per construct).",
    "ncbi_link": "LUC: 
T28: 10155
TRIM28: 10155"
  },
  {
    "caption": "C, Metagene profiles after CUT&RUN sequencing of TRIM28 in untransduced A375 cells and of RNAPII in A375 cells transduced with shT28-1 or shSCR lentivirus. The lower panel is focused on the TRIM28 metagene profile to clearer depict its binding profile around TSS.",
    "ncbi_link": "T28: 10155
TRIM28: 10155"
  },
  {
    "caption": "E, TRIM28 and RNAPII occupancy at EGR1 and JUNB in A375 as determined by CUT&RUN sequencing (PI = length-normalized pause index).",
    "ncbi_link": "EGR1: 1958
JUNB: 3726"
  },
  {
    "caption": "F, Immunoblots against TRIM28 and JUNB in A375, A2058 and SK-MEL-28 cells transduced with shSCR, shT28-1 or shT28-2 lentivirus. Results are expressed as mean ±SEM from three biological replicates (n=3). G, Densitometry of JUNB and TRIM28 protein levels (relative to β-actin) in A375, A2058 and SK-MEL-28 melanoma cells based on the immunoblots in F. One-way ANOVA with Dunnett's post hoc test was used for statistical testing.",
    "ncbi_link": "T28: 10155"
  },
  {
    "caption": "A, Immunoblotting to determine the overexpression of JUNB in A375 cells transduced with pBABE-JUNB.",
    "ncbi_link": "JUNB: 3726"
  },
  {
    "caption": "B, Volcano plot displaying differentially expressed genes after RNA-seq analysis of JUNB overexpressing A375 cells (pBABE-JUNB) and control A375 cells transduced with empty pBABE vector (EV) (n=4). Genes induced after JUNB overexpression are highlighted in yellow, and gene suppressed after JUNB overexpression are highlighted in blue.",
    "ncbi_link": "JUNB: 3726"
  },
  {
    "caption": "D, Heatmap displaying the induction of CXCL1 and CXCL8, and suppression of YAP1 target genes, in A375 cells overexpressing JUNB.",
    "ncbi_link": "CXCL1: 2919
CXCL8: 3576
JUNB: 3726"
  },
  {
    "caption": "E, Expression of YAP1 signature genes in A375 cells after transduction with dCas9-KRAB lentiviruses expressing gRNA targeting JUNB (gJUNB-1 or gJUNB-2) or control gRNA (gEGFP). qRT-PCR was used to determine expression levels, and results are expressed as mean ±SEM from three biological replicates (n=3).",
    "ncbi_link": "EGFP: 
Cas9: 69900935
JUNB: 3726
YAP1: 10413"
  },
  {
    "caption": "F, Quantification of Matrigel invasion experiments with A375 cells transduced with pBABE-JUNB (JUNB) or pBABE empty vector (EV) retrovirus. Results are expressed as mean ±SEM from three biological replicates (n=3) and the two-sided unpaired t-test was used. G, Representative images from Matrigel invasion assays in (F). Scale bar is 60 μm.",
    "ncbi_link": "JUNB: 3726"
  },
  {
    "caption": "H, Quantification of Matrigel invasion experiments with A375 cells transduced with dCas9-KRAB lentiviruses expressing gRNA targeting JUNB (gJUNB-1) or control gRNA (gEGFP). Results are expressed as mean ±SEM from three biological replicates (n=3) and the two-sided unpaired t-test was used. I, Representative images from Matrigel invasion assays in (H). Scale bar is 60 μm.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
JUNB: 3726"
  },
  {
    "caption": "J, Quantification of Matrigel invasion with A375 cells transduced with dCas9-KRAB lentiviruses expressing gRNA targeting JUNB (gJUNB-1) or a control gRNA (gEGFP), and then transfected with non-targeting siRNA (siNTC) or siRNA targeting YAP1 (siYAP1) and TAZ (siTAZ). Results are expressed as mean ±SEM from three biological replicates (n=3). One-way ANOVA and the Tukey post hoc test were used for statistical testing.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
JUNB: 3726
TAZ: 6901
YAP1: 10413"
  },
  {
    "caption": "K, Tumor growth after subcutaneous injection of 2.0x106 A375 cells transduced with pBABE-JUNB (JUNB) or pBABE empty vector (EV) retrovirus (n=10 mice per group). Results are expressed as mean ±SEM. Repeated-measures ANOVA was used for the statistical test of tumor growth. L, Tumor weight after the subcutaneous injection of A375 cells as shown in (K). Tumor weight was analyzed 20 days after subcutaneous injection. Results are expressed as mean ±SEM. The two-sided Mann-Whitney U-test was used for the statistical test of tumor weight.",
    "ncbi_link": "JUNB: 3726"
  },
  {
    "caption": "J: qPCR analysis of IL-6 in msEGCs that were treated for 6h with ATP.",
    "ncbi_link": "IL-6: 16193"
  },
  {
    "caption": "D: P2X2 antagonism of ATP induced mRNA expression of IL-6, GFAP and RCAN by qPCR in msEGCs. Cells were treated with the P2X2-antagonist PSB-1011 (20µM) alone or together with ATP (10µM) for 6h.",
    "ncbi_link": "GFAP: 14580
IL-6: 16193
RCAN: 54720"
  },
  {
    "caption": "F: P2X2-siRNA reduces P2X2-mRNA and dampens the gliosis gene expression after ATPɣS (100µM) treatment for 6h.",
    "ncbi_link": "P2X2: 231602"
  },
  {
    "caption": "G: P2X2-siRNA reduces IL-6 release after ATPɣS treatment (10µM, 100µM) for 6h.",
    "ncbi_link": "P2X2: 231602"
  },
  {
    "caption": "I: PSB-1011 (20μM) treatment inhibited ATP-triggered calcium responses in HEK cells transfected with P2X2. Data are represented as ΔF/F0 +SEM; n=102 HEK cells. J: The P2X2 receptor antagonist PSB-0711 (20μM) nearly abolished the ATP-triggered calcium response in HEK cells transfected with P2X2. n=219 HEK cells.",
    "ncbi_link": "P2X2: 22953"
  },
  {
    "caption": "(G) Human ILC2 sorted from  peripheral blood   and in vitro expanded were transduced with Luc-sh or Maf-sh as in (C). hILC2s were then stimulated for 48h with IL-33 and the concentration of the indicated cytokines in the supernatants was measured (Multiple Mann-Whitney tests, *p<0.05, **p<0.01) Bars represent mean ± SEM. Data information: Each dot represents data from one individual mouse or from one donor.",
    "ncbi_link": "Luc: 
Maf: 4094"
  },
  {
    "caption": "(E) ChIP-qPCR  analysis of c-Maf occupancy on IL-4,  IL-5  and IL-13 promoters in untreated mouse  and human ILC2s (IL-2 stimulation) and in mouse  and human ILC2s  treated with  IL-33 (n=3 biological replicates).",
    "ncbi_link": "IL-13: 3596
IL-4: 3565
IL-5: 3567"
  },
  {
    "caption": "(E, F) c-Maf  quantification by qPCR (E) and cytokine concentration (F) in the supernatants of adult and cord blood ILC2s  unstimulated, stimulated for 3h with PMA-Ionomycin  (3h stim) and stimulated for an overnight with  IL-33 and then 3h with PMA-Ionomycin  (o.n. stim). ILC2s  were sorted from 3 different donors. (E) Multiple T tests, unstimulated: p=0.000101; 3h stim: p=0.0036. (F) Multiple T tests, IL-13: p=0.022;  IL-5: p=0.015 (*p<0.05). Bars represent mean ± SEM.",
    "ncbi_link": "c-Maf: 4094"
  },
  {
    "caption": "(A) Representative images of COS7 cells expressing GFP-COP1 (green) co-transfected with empty vector or the indicated TRIB1-FLAG construct (red). Cells were stained with anti-FLAG (Sigma) and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm. See also Appendix Fig S1B for western blots showing the expression levels of the constructs used.",
    "ncbi_link": "FLAG: 
TRIB1: 10221"
  },
  {
    "caption": "(B) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 in (A). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance relative to GFP-COP1 with empty vector was calculated using the Student t test (****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(A) Representative images of COS7 cells expressing COP1-3xFLAG (green) co-transfected with empty vector, GFP, or the indicated GFP-TRIB1 constructs (red). Cells were stained with anti-FLAG (Sigma) and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
TRIB1: 10221"
  },
  {
    "caption": "(B) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of COP1-3xFLAG in (A). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance relative to GFP-COP1 with empty vector was calculated using the Student t test (*p < 0.01; **p < 0.001; ***p < 0.0001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(C) Representative images of COS7 cells expressing GFP-COP1 (green) co-transfected with empty vector, TRIB1-FLAG, TRIB2-FLAG, or TRIB3-FLAG (red). Cells were stained with anti-FLAG (Sigma) and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "FLAG: 
TRIB1: 10221
TRIB2: 28951
TRIB3: 57761"
  },
  {
    "caption": "(D) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 in (C). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance relative to GFP-COP1 with empty vector was calculated using the Student t test (ns, not significant; ***p < 0.0001; ****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(B) Coimmunoprecipitation of COP1 WD40 mutants with TRIB1 from COS7 cells transiently transfected with the indicated GFP-COP1 constructs and untagged TRIB1.",
    "ncbi_link": "GFP: 
COP1: 64326
TRIB1: 10221"
  },
  {
    "caption": "(C) Representative images of COS7 cells transiently transfected with the indicated GFP-COP1 constructs (green). Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(D) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 constructs in (C). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance relative to GFP-COP1 WT was calculated using the Student t test (***p < 0.0001; ****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(B) Representative images of COS7 cells transiently transfected with GFP-COP1 WT or GFP-COP1 4A (green). Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(C) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 in (B). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance relative to GFP-COP1 WT was calculated using the Student t test (****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(F) Representative images of COS7 cells transiently transfected with the indicated GFP-COP1 constructs (green) and empty vector or TRIB1-FLAG (red). Cells were stained with anti-FLAG (Sigma) and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "FLAG: 
GFP: 
COP1: 64326
TRIB1: 10221"
  },
  {
    "caption": "(G) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 constructs in (F). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance was calculated using the Student t test (ns, not significant, ***p < 0.0001; ****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(A) Representative images of COS7 cells transiently transfected with GFP-COP1 WT or GFP-COP1 NESmut (V238A/L242A) (green) and empty vector or 3xFLAG-CRM1 (grayscale). Cells were stained with anti-FLAG (Cell Signaling) and anti-rabbit Alexa Fluor 680. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "FLAG: 
GFP: 
COP1: 64326
CRM1: 7514"
  },
  {
    "caption": "(B) Representative images of COS7 cells transfected with GFP-COP1 WT (green), the indicated TRIB1-HA constructs (red), and empty vector or 3xFLAG-CRM1 (grayscale). Cells were stained with anti-FLAG (Cell Signaling), anti-HA (Sigma), anti-rabbit Alexa Fluor 680, and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
COP1: 64326
TRIB1: 10221
CRM1: 7514"
  },
  {
    "caption": "(C) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 constructs in (A) and (B). Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance was calculated using the Student t test (ns, not significant; *p < 0.01; ****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(E) Representative images of COS7 cells transiently transfected with the indicated GFP-COP1 constructs (green) and 3xFLAG-CRM1 (grayscale). Cells were stained with anti-FLAG (Sigma) and anti-mouse Alexa Fluor 568. Nuclei were counterstained with DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "FLAG: 
GFP: 
COP1: 64326
CRM1: 7514"
  },
  {
    "caption": "(F) Quantification of the average ratio of nuclear/cytoplasmic fluorescence of GFP-COP1 constructs in (E) and Figure EV6C. Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed. Significance was calculated using the Student t test (ns, not significant; ****p < 0.00001).",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(G) Quantification of percentage of cells observed in (E) and Figure EV6C with the indicated GFP-COP1 construct exhibiting nuclear (Nuc), nuclear and cytoplasmic (Nuc/Cyt), or cytoplasmic (Cyt) localization. Mean values ± S.E.M. are shown for three independent experiments where 50 individual cells per experiment were analyzed.",
    "ncbi_link": "GFP: 
COP1: 64326"
  },
  {
    "caption": "(B) Genotyping of Brd4fl/fl mice with ERT2-Cre (Cre) or without ERT2 -Cre (+/+). Tamoxifen treatment deleted 2.2 kb Brd4fl/fl fragment from Cre/+ and Cre/Cre mice (top). Cre/+, Cre/Cre and +/+ mice were confirmed by the presence of ERT2 -Cre band (Cre), or its absence (WT) (bottom).",
    "ncbi_link": "Brd4: 57261
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "(C) WT and Brd4 KO cells were tested for mRNA (left) and the protein (right) by qRT-PCR and immune blot assays. Values represent the average of three experiments +/- SD.",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "(D) Vav-cre mediated Brd4 depletion was verified for cells from Brd4fl/fl Vav-Cre mice (fetal liver or spleen) by qRT-PCR and Immunoblot (left and right). Values represent the average of three experiments +/- SD.",
    "ncbi_link": "Brd4: 57261
cre: 2777477
Cre: 2777477
Vav: 22324"
  },
  {
    "caption": "(A) Flow cytometry profiles of peritoneal cells from WT and KO mice stained for CD19 and F4/80 (left). FACS profile of CD19- subset showing CD11b+ and F4/80+ subsets of cells from WT and KO macrophage populations (middle). Cell numbers (right) represent the average of 4 WT and 4 Brd4 KO mice +/- S.D. Note a reduction in F4/80+ cells from Brd4 KO peritoneum.",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "(B) Flow cytometry profiles of peritoneal cells from IL-4C injected WT and KO mice (left). Cell numbers (right) represent the average of 4 WT and 4 Brd4 KO mice +/- S.D.",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "(D) Microarray analysis of macrophage gene expression in IL-4C treated WT or Brd4 KO mice. Macrophages were isolated from peritoneal cells by the MACS system. Differentially expressed genes were identified with a cut-off line of log 2fold change >2 difference with p value of < 0.05. Red dots indicate differentially expressed genes (KO vs WT) and gray dots are those below the cut-off line.",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "(E) qRT-PCR analysis of genes representative of the BRD4 independent group (unaffected by KO), dependent group (downregulated by KO) or upregulated by KO. Data were obtained from three independent macrophage samples. Values are the average of 3+/- S.D.",
    "ncbi_link": "BRD4: 57261"
  },
  {
    "caption": "(E) Binding of BRD4 and PolII and distribution of histone marks (H3K27ac and H3K9ac) on BRD4 dependent and independent genes (from -5kb of TSS to +5kb of transcription end site (TES)) in UT and LPS treated WT and KO macrophages. Normalized ChIP-seq signals (rpm/bp) are shown on the Y axis. Arrows show reduced signals in Brd4 KO macrophages.",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "(F) Gene tracks of normalized island-filtered ChIP-seq peaks for BRD4, Pol II, and indicated histone modification marks, along with RNA-seq peaks for a BRD4 independent gene (Ccl9) and a BRD4 dependent gene (Fcgr2b). Values on the Y axis are normalized ChIP-seq signals (rpm/bp).",
    "ncbi_link": "BRD4: 57261
Ccl9: 20308
Fcgr2b: 14130"
  },
  {
    "caption": "(C) Examples of nearest genes that gained or lost SEs upon LPS treatment. Gene tracks for gained and lost loci (near Tnf and Csf1r) showing clusters of BRD4, Pol II and H3K27ac signals. Red bar represents SE length.",
    "ncbi_link": "Csf1r: 12978
Tnf: 21926"
  },
  {
    "caption": "(C) Gene tracks of BRD4 and p65 ChIP-seq peaks and RNA-seq profiles on a BRD4 independent gene (Il1b), a gene upregulated in Brd4KO macrophages (Ccl7), and a BRD4 dependent gene (Ptgs2).",
    "ncbi_link": "Brd4: 57261
Ccl7: 20306
Il1b: 16176
Ptgs2: 19225"
  },
  {
    "caption": "(D) Enhancers ranked by increasing p65 signals in WT (left) and Brd4 KO macrophages (right).",
    "ncbi_link": "Brd4: 57261"
  },
  {
    "caption": "A. NLK but not kinase-negative NLK (Flag-NLK-KM; K155M) caused mobility shift of EGFP-YAP. EGFP-YAP was transfected with empty vector, Flag-NLK-WT, or Flag-NLK-KM into HEK293T cells. Mobility shift was shown by immunoblotting.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "B. NLK phosphorylates YAP in vitro. Flag-NLK-WT, or Flag-NLK-KM was immunoprecipitated with anti-Flag antibody from cell lysates of HEK293T cells transfected with each plasmid and subjected to in vitro kinase assay with bacterially purified GST-YAP in the presence of [32P-ATP]. Phosphorylation of GST-YAP and autophosphorylation of NLK were examined by autoradiography (top panel), and Coomassie Blue staining showed similar levels of GST-YAP and Flag-NLK (bottom panel).",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "B. NLK-WT but not NLK-KM reduces Ser127 phosphorylation of endogenous YAP. Cell lysates from HEK293 cells transfected with empty vector (-), Flag-NLK-WT, or Flag-NLK-KM were immunoblotted with antibodies shown in the figure (left panel). The ratio of p-YAP(S127) or p-YAP(S397)/total-YAP of three independent western blots was quantified (right panel). Data are presented as mean ± sem. **P < 0.01. Student t-test was used for statistical analysis.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "C. Deficiency of NLK leads to increased YAP phosphorylation at Ser127. Lysates from wild type and two independent NLK knockout HEK293 cells were immunoblotted with antibodies indicated in the figure (left panel). The ratio of p-YAP(S127) or p-YAP(S397)/total-YAP of three independent western blots was quantified (right panel). Data are presented as mean ± sem. *P < 0.05 and **P < 0.01. Student t-test was used for statistical analysis.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "D. Ectopic expression of NLK attenuates YAP phosphorylation at Ser127 while increases phosphorylation at Ser128. Cell lysates from HEK293 cells transfected with empty vector (-), Flag-NLK-WT, or Flag-NLK-KM were immunoblotted with antibodies shown in the figure.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "E. Substitution of Ser127 with alanine enhances phosphorylation at Ser128, and vice versa. Cell lysates from HEK293T cells transfected with empty vector (-), EGFP-YAP, EGFP-YAP-S127A, or EGFP-YAP-S128A were immunoblotted with antibodies shown in the figure.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "A. Ectopic expression of NLK attenuates interaction between YAP and 14-3-3. Lysates from HEK293T cells transfected with plasmids indicated in the figure were immunoprecipitated with anti-HA antibody and immunoblotted with anti-GFP antibody (top two panels). Whole cell lysates (WCL) were immunoblotted with antibodies shown in the figure (bottom three panels).",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "B. Deficiency of NLK leads to increased interaction between YAP and 14-3-3. Lysates from NLK knockout HEK293 cells were immunoprecipitated with anti-YAP antibody and immunoblotted with anti-14-3-3 antibody (top two panels). WCL were immunoblotted with antibodies indicated in the figure (bottom three panels).",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "D. Phosphorylation status of Ser127 or Ser128 determines subcellular localization of YAP. Immunofluorescence analysis was performed in HeLa cells transfected with EGFP-YAP, EGFP-YAP-S127A, EGFP-YAP-S128A, or EGFP-YAP-S128D at high cell density. Figure shows a representative of multiple areas. Nuclei were stained with Hoechst 33342. Scale bars: 20 μm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "E. NLK knockout leads to increased cytoplasmic localization of endogenous YAP. Immunoblot analysis shows significant reduction of NLK level in NLK knockout HEK293 cell pools (top panel).",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "E. NLK knockout leads to increased cytoplasmic localization of endogenous YAP. To determine subcellular localization of YAP indirect immunofluorescence analysis was performed in NLK knockout HEK293 cell pools (bottom panel). Figure shows a representative of multiple areas. Nuclei were stained with DAPI. Scale bars: 20 μm.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "C. Level of endogenous NLK mRNA is unaffected, whereas the expression of YAP target genes was reduced, at high cell density. Quantitative real-time PCR analyses for expression of AMOTL2, CTGF, CYR61, and NLK in low (LD) and high density (HD) NIH3T3 cells were performed. Quantification of AMOTL2, CTGF, CYR61, and NLK mRNA was normalized with the level of Gapdh. Data represent average values from a representative of multiple experiments performed in triplicate. Error bars indicate standard deviations of triplicate measurements. Data are presented as mean ± sem. *P < 0.05 and ***P < 0.005. Student t-test was used for statistical analysis.",
    "ncbi_link": "AMOTL2: 56332
CTGF: 14219
CYR61: 16007
NLK: 18099"
  },
  {
    "caption": "A. Knockout of NLK reduces the interaction between endogenous YAP and TEAD. Lysates from NLK knockout HEK293 cells were immunoprecipitated with anti-TEAD1 antibody and immunoblotted with anti-TEAD1 antibody or anti-YAP antibody (top panel). Whole cell lysates (WCL) were immunoblotted with antibodies indicated in the figure.",
    "ncbi_link": "NLK: 51701"
  },
  {
    "caption": "C. Downregulation of nemo with RNAi achieved in the posterior compartment of wing imaginal discs (co-expression of GFP serves to mark the posterior compartment) using the hh-Gal4 driver results in decreased expression of the Yorkie target gene DIAP1. Two different RNAi constructs produce similar effect. Panels below show Z-stacks of magnified areas around the A/P border (left). Quantification of DIAP1 levels achieved upon posterior-downregulation of nemo, measured as normalized posterior-to-anterior levels and compared to similar expression of GFP. Data are present as mean ± sem, n=8 discs. *P < 0.05. Student t-test was used for statistical analysis (right). Scale bars: 50 µm.",
    "ncbi_link": "hh: 42737
nemo: 38890"
  },
  {
    "caption": "D. Yorkie is epistatic to Nemo: co-overexpression of the constitutively active mutant yki[S168A] together with nmo-RNAi produces typical yki[S168A] phenotypes: severe overgrowth of the affected area with concomitant increase in yki target gene expression (DIAP1). Due to lethality of the hh-Gal4-driven co-overexpression, another posterior driver en-Gal4 was used instead; anti-Hh staining (green) was used to mark the posterior compartment (left panel). Quantification posterior DIAP1 levels in UAS-RNAi-nemo; en-Gal4 and UAS-yki[S168A]; en-Gal4, presented as in (C); n= 3-6 discs. Posterior DIAP1 levels in UAS-RNAi-nemo; en-Gal4 are also significantly different from control UAS-GFP; en-Gal4 discs (right panel). Data are presented as mean ± sem. ***P < 0.005. Student t-test was used for statistical analysis (right). Scale bars: 50 µm.",
    "ncbi_link": "en: 36240
hh: 42737
nemo: 38890
nmo: 38890
yki: 37851"
  },
  {
    "caption": "E. Mutant forms of YAP which have different phosphorylation status of Ser127 or S128 differentially rescue retarded wound healing caused by NLK knockout. HEK293 wild type or HEK293 NLK knockout cells were transfected with indicated plasmids (\"EV\" stands for \"empty vector\"), and the wounded areas after 0 and 24 hr were measured by using the TScratch program (left panel). Graphs show percentage of unfilled areas at 24 hr compared to 0 hr, and average values from a representative of multiple experiments performed in triplicate (right-top panel).",
    "ncbi_link": "NLK: 51701
YAP: 10413"
  },
  {
    "caption": "E. Mutant forms of YAP which have different phosphorylation status of Ser127 or S128 differentially rescue retarded wound healing caused by NLK knockout. HEK293 wild type or HEK293 NLK knockout cells were transfected with indicated plasmids (\"EV\" stands for \"empty vector\"), and the wounded areas after 0 and 24 hr were measured by using the TScratch program (left panel). Graphs show percentage of unfilled areas at 24 hr compared to 0 hr, and average values from a representative of multiple experiments performed in triplicate (right-top panel). Lysates were immunoblotted with antibodies indicated in the figure (right-bottom panel). Error bars indicate standard deviations of triplicate measurements. Data are presented as mean ± sem. *P < 0.05. Student t-test was used for statistical analysis (right). Scale bars: 200 μm.",
    "ncbi_link": "NLK: 51701
YAP: 10413"
  },
  {
    "caption": " (B) When transposon insertion libraries subjected to ampicillin resistance selection, a substantial increase in transposon insertion frequency in the pstSCA genes was observed in strains containing the protein folding sensor (pBR322 bla::Im7 L53A I54A) relative to a strain containing just pBR322. Transposon insertion frequency increased 21-, 24-, and 8-fold in the pstS, pstA, and pstC genes, respectively, compared to the insertion frequency found with no ampicillin selection. ",
    "ncbi_link": "Im7: 
bla: 59687646///59688953///59682938///59688725///59687632
pstA: 948239
pstC: 948238
pstS: 948237"
  },
  {
    "caption": " (A) To verify that disruption of the pst genes is sufficient to increase ampicillin resistance of strains containing the pBR322 bla::Im7 L53A I54A folding biosensor and to test which of the genes in the pst operon are sufficient for this effect, pBR322 and pBR322 bla::Im7 L53A I54A were transformed into strains containing in-frame deletion mutants of each of the pst genes (pstS, pstC, and pstA, respectively). The deletion mutants of each of these pst genes showed higher ampicillin resistance than did the WT strain MG1655 in the presence of pBR322 bla::Im7 L53A I54A, but did not shower higher ampicillin resistance in the presence of pBR322. ",
    "ncbi_link": "Im7: 
bla: 59687646///59688953///59687632///59688725///59682938
pstA: 948239
pstC: 948238
pstS: 948237"
  },
  {
    "caption": " (B) Levels of β-lactamase (Bla) and β-lactamase-Im7 L53A I54A were detected by Western blotting using a polyclonal antibody recognizing β-lactamase in the WT strain MG1655 and in isogenic strains containing insertions in the pstSCA genes (CL248 (pstS::Tn5), CL249 (pstC::Tn5), CL250 (pstA::Tn5)). Maltose binding protein (MBP) was used as a control. ",
    "ncbi_link": "β-lactamase: 59687632
pstA: 948239
pstC: 948238
pstS: 948237"
  },
  {
    "caption": " (C) β-lactamase enzymatic activities present in periplasmic extracts of the Im7 folding biosensor were monitored in pst WT and pstSCA mutant strains using a spectrophotometric assay. Data are represented as mean ± SEM from three technical replicates (unpaired t-test,** P<0.01, *** P<0.001 comparison to MG1655; ns, not significant). ",
    "ncbi_link": "Im7: 
pstS: 948237"
  },
  {
    "caption": " (D) To test if levels of the Im7 L53A I54A protein itself, in the absence of the fusion, were also higher in the pstA mutant, expression of the Im7 L53A I54A protein from the IPTG-inducible plasmid pCDFTrc was induced using IPTG concentrations ranging from 0-5 mM. Periplasmic fractions were isolated and examined by SDS-PAGE and subsequent Coomassie staining to determine overall protein expression patterns. Im7 L53A I54A levels were determined by Western blotting using an antibody for Im7. MBP was used as a loading control. Im7 L53A I54A was increased in the pstA strain relative to the WT control strain. Coomassie staining revealed that a number of periplasmic proteins, including UgpB, were also induced in the pstA strain. ",
    "ncbi_link": "pstA: 948239"
  },
  {
    "caption": " (A) MG1655 WT, single mutants of pstA and ugpB, and a double mutant of pstA ugpB were transformed with pBR322 and various pBR322-based folding biosensor constructs. The transformants were examined by a spot titer assay on LB agar plates containing various ampicillin concentrations. Strains containing pBR322 bla::Im7 L53A I54A gain considerable ampicillin resistance in the presence of a pstA mutation (compare uppermost left and right panels). This resistance is completely lost upon transducing in a ugpB mutation (compare next panels down), showing that ugpB is responsible for the resistance gained by the pstA mutation. ",
    "ncbi_link": "Im7: 
bla: 59687646///59688953///59687632///59688725///59682938
pstA: 948239
ugpB: 947962"
  },
  {
    "caption": " (B) Ampicillin sensitivity conferred by a ugpB deletion mutant (CL543) is complemented by UgpB expression from the arabinose inducible expression vector pBAD33 ugpB (pCL1). ",
    "ncbi_link": "ugpB: 947962
UgpB: 947962"
  },
  {
    "caption": " (C) UgpB expression is sufficient to lead to higher levels of Im7 L53A I54A protein. Im7 L53A I54A and UgpB were expressed in a ugpB mutant strain (CL543) from pCDFTrc and pTrc99a vectors, respectively, both of which have an IPTG-inducible promoter. Periplasmic fractions were isolated and examined by Western blotting. "-" indicates strains containing empty vector and "+" indicates strains containing a recombinant plasmid encoding either Im7 L53A I54A or UgpB. MBP was used as a loading control. Data information: These experiments were repeated twice with similar results and one representative is shown. ",
    "ncbi_link": "Im7: 
ugpB: 947962
UgpB: 947962"
  },
  {
    "caption": "(A) UgpB overexpression confers bile salt resistance, and a ugpB deletion mutant is slightly CHO sensitive.",
    "ncbi_link": "ugpB: 947962"
  },
  {
    "caption": "D) Expression of the WT or R527A mutant GFP-KNL2 in KNL2 conditional knock out chicken DT40 cells (cKO-KNL2). Expression of full-length KNL2 WT was conditionally turned off by tetracycline (tet) addition in cKO-KNL2 cells (None). GFP-fused KNL2 WT or R527A mutant was stably expressed in the cKO-KNL2 cells. These cells were cultured in the presence or absence of tet (+tet: KNL2 OFF or −tet: KNL2 ON) for 48 h. α-Tubulin (Tub) was probed as a loading control.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "E) Localization analyses of GFP-fused KNL2 WT or R527A mutant (green). CENP-T was stained as a kinetochore marker (red), and DNA was stained using DAPI (blue). Magnified views are shown in insets. Scale bar indicates 10 μm.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "F) Growth of the cKO-KNL2 cells expressing GFP-fused KNL2 WT or R527A mutant. The upper panel shows examined cell numbers at the indicated time after tet addition (+tet: KNL2 OFF). The cell numbers were normalized to those at 0 h for each line and plotted as relative cell number. The lower panel shows examined untreated cells (-tet: KNL2 ON). Parental cKO-KNL2 chicken DT40 cells (None) were also examined.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "D) Expression of GFP-KNL2 WT or CENP-A C-terminal tail binding mutants in cKO-KNL2 cells. Expression of full-length KNL2 WT was conditionally turned off by tetracycline (tet) addition to the cKO-KNL2 cells (None). GFP-fused KNL2 WT, F535A, W536A or F535A/W536A was stably expressed in the cKO-KNL2 cells. These cells were cultured in the presence or absence of tet (+tet: KNL2 OFF or −tet: KNL2 ON) for 48 h. α-Tubulin (Tub) was probed as a loading control.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "E) Localization analyses of GFP-fused KNL2 WT and F535A, W536A or F535A/W536A mutant (green). CENP-T was stained as a kinetochore marker (red), and DNA was stained using DAPI (blue). Magnified views are shown in insets. Scale bar indicates 10 μm.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "F) Growth of the cKO-KNL2 cells expressing GFP-fused KNL2 WT or each CENP-A C-terminal tail binding mutant. The upper panel shows examined cell numbers at the indicated time after tet addition (+tet: KNL2 OFF). The cell numbers were normalized to those at 0 h for each line and plotted as relative cell number. The lower panel shows examined untreated cells (-tet: KNL2 ON). Parental cKO-KNL2 chicken DT40 cells (None) were also examined.",
    "ncbi_link": "GFP: 
CENP-A: 100113359
KNL2: 423593"
  },
  {
    "caption": "A) Immunostaining with anti-Mis18α antibody in AID-based KNL2 knockout cells expressing GFP fused KNL2 wild type or each KNL2 mutant in the presence of IAA for 15 h. Clear colocalization of KNL2 signals with Mis18α was observed (Insets). DNA was stained with DAPI. Scale bar indicates 10 µm.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "B) AID-based KNL2 knockout cells expressing GFP fused each KNL2 mutant and SNAP-tagged CENP-A were used. After addition of IAA, SNAP-CENP-A signals were visualized by TMR-Star staining. CENP-T was stained as a kinetochore marker. Representative images were presented. Mitotic centromere localization of each KNL2 mutant was shown as a merged image (Insets): SNAP-CENP-A (red) and each KNL2 mutant (green). DNA was stained with DAPI. Scale bar indicates 10 µm.",
    "ncbi_link": "GFP: 
KNL2: 423593"
  },
  {
    "caption": "A) KNL2 (red) localization in CENP-C conditional knockout chicken DT40 cells (cKO-CENP-C) with or without CENP-C expression. DNA was stained with DAPI (blue). CENP-T was stained as a kinetochore marker (light blue). Scale bar indicates 10 μm.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "B) KNL2 intensities were evaluated in six cells before and after CENP-C knock out. KNL2 signal intensities on the mitotic centromeres (14-90 centromeres) in each cell were plotted with the average and the standard deviation. The ratio of KNL2 intensities between cells before and after CENP-C knock out was estimated. KNL2 intensities were reduced by ~55%, when CENP-C was knocked out.",
    "ncbi_link": "CENP-C: 395922"
  },
  {
    "caption": "C) Competitive pull-down assays for the CENP-A nucleosome binding of ggKNL2 and ggCENP-C. A complex of GST-KNL2456-560 with the CENP-A nucleosome (CA-nuc) was incubated in the absence or presence of MBP-CENP-C619-690 (right panel) or phosphorylated MBP-CENP-C619-690 (middle panel) and pulled down by GST affinity. The concentration of CENP-C619-690 was increased from 0 μM to 1 μM (lanes 3-7). The ratio of band intensities of pull-downed histones (*) to GST-KNL2456-560 in each lane (lanes 3-7) was estimated and presented in the bar graph (left panel). Data are mean with standard deviations calculated from the technical replicates, n=3.",
    "ncbi_link": "GST: 
KNL2: 423593"
  },
  {
    "caption": "A SHP1immunoprecipitation (IP) from Jurkat 1G4‐CD8 cells. Upper panel of immunoblots shows expression levels in the input lysates, and isolated protein complexes are shown at the bottom. Rabbit IgGIP (isotype) is shown as control.",
    "ncbi_link": "CD8: 925"
  },
  {
    "caption": "B Lentiviral knock‐down/re‐expression constructs for THEMIS‐wt‐Strep and THEMIS‐dPRR1‐Strep in 1G4‐CD8 cells. Knock‐down/re‐expression constructs are based on shTHEMIS‐128476. Red arrowheads indicate the specific signal for endogenous THEMIS and re‐expressed THEMIS‐Strep. The higher molecular weight band observed in all lanes is a non‐specific signal.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "C Streptactinpull‐downs (PDs) of THEMIS‐Strep from 1G4‐CD8 cells. Cells as described in (B) were stimulated with 6V tetramers, followed by Streptactin PDs of THEMIS and immunoblot analysis of isolated protein complexes. Separate experiments for SHP1 and SHP2 are shown.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "D SHP1IP in the presence and absence of SHP1 tail phosphorylation. SHP1 was immunoprecipitated from J.CaM1.6LCK‐Tet cells. Where indicated, LCK expression was induced with doxycycline prior to the experiment or Src‐kinase inhibitor PP2 was used to abolish residual SHP1‐pY564. The upper panel of immunoblots shows the effect of LCK activity on SHP1‐pY564 levels. The red arrowhead indicates residual pY564. Isolated protein complexes are shown in the lower panels.",
    "ncbi_link": "Tet: 
LCK: 3932"
  },
  {
    "caption": "E In vitro phosphatase treatment of the THEMIS:GRB2:SHP1 complex. Bead‐bound THEMIS‐Strep complexes from 1G4‐CD8 cells were incubated in alkaline phosphatase (AP) buffer in the absence (lane 1) or presence of AP (lane 2), or left completely untreated (lane 3), prior to washing and elution.",
    "ncbi_link": "CD8: 925"
  },
  {
    "caption": "F Anti‐HAIP from HEK293 cells transfected with HA‐SHP1 and GRB2‐Myc constructs. GRB2 mutants used: W36K, N‐SH3 mutant; W193K, C‐SH3 mutant. Upper panels show expression levels in the input; isolated proteins complexes are shown at the bottom. Relative amounts of GRB2‐Myc are normalized to the bait HA‐SHP1.",
    "ncbi_link": "GRB2: 2885
SHP1: 5777"
  },
  {
    "caption": "G Far‐Western blot of GRB2‐SH3 domains binding to full‐length SHP1. HA IPs from empty vector or HA‐SHP1‐transfected HEK293 cells were subjected to far‐Western blotting using recombinant GST‐tagged N ‐or C‐SH3 domains of GRB2. GST alone served as a background control. Blots were re‐probed for SHP1 loading for normalization of anti‐GST signals. Data shown are representative of three independent experiments.",
    "ncbi_link": "GRB2: 2885"
  },
  {
    "caption": "A Lentiviral knock‐down (KD) of THEMIS expression in 1G4‐CD8 cells. The efficiency of the THEMIS KD was assessed using immunoblotting.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "B Phospho‐flow cytometry analysis of pERK responses in THEMIS KD cells. 1G4‐CD8 control and THEMIS KD cells were stimulated with NY‐ESO‐1 pMHC tetramers and analysed for ERK phosphorylation using flow cytometry. Data shown are representative of three independent experiments.C Quantification of pERK‐positive cells from (B). Data from three independent experiments were used in the analysis. n = 3, means ± SEM are shown; two‐tailed unpaired Student's t‐test, *P 0.05, **P 0.01.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "A 1G4‐CD8 control and THEMIS KD cells were stimulated with NY‐ESO‐1 pMHC tetramers and analysed for pY142‐CD3‐ζ phosphorylation by flow cytometry. Data shown are representative of three independent experiments.B Quantification of pY142‐CD3‐ζ responses of cells from (A). Data from three independent experiments were used in the analysis. Responses are expressed as percentage of the positive control sodium pervanadate. n = 3, means ± SEM are shown; two‐tailed unpaired Student's t‐test, **P 0.01.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "A Lentiviral knock‐down of THEMIS expression in primary humanCD4+T cells. Following transduction, cells were expanded on CD3/CD28 beads in the presence of exogenous IL‐2 and analysed for THEMIS KD by immunoblotting on day 4 post‐transduction. Data shown are representative of three independent experiments.",
    "ncbi_link": "THEMIS: 387357"
  },
  {
    "caption": "B pERK response in THEMIS KD humanCD4+T cells. Transduced CD4+ cells were removed from beads, rested overnight and stimulated with CD3 mAb for the indicated time points. ERK phosphorylation was assessed by immunoblotting. Data shown are representative of three independent experiments.",
    "ncbi_link": "THEMIS: 387357"
  },
  {
    "caption": "C Expression of CD25 and CD69 surface markers of THEMIS KD humanCD4+T cells was assessed on day 4 post‐transduction by flow cytometry. Data shown are representative of three independent experiments.",
    "ncbi_link": "THEMIS: 387357"
  },
  {
    "caption": "D CD69 up‐regulation on re‐stimulated THEMIS KD CD4+T cells. CD3/CD28 beads were removed on day 1 post‐transduction, and cells were cultured in IL‐2 and IL‐7. After removal of cell debris at day 4, cells were restimulated with CD3/CD28 beads at the indicated bead to cell ratio. CD69 surface expression was assessed by flow cytometry 24 h later. Data shown are representative of two independent experiments. n = 3, means ± SD are shown; two‐tailed unpaired Student's t‐test, *P 0.05, ***P 0.001.",
    "ncbi_link": "THEMIS: 387357"
  },
  {
    "caption": "B Annexin‐V staining of THEMIS KD 1G4‐CD8 cells. THEMIS KD and control 1G4‐CD8 cells were stimulated for 24 h with plate‐bound 6V tetramers. Annexin‐V surface expression was analysed by flow cytometry and is shown as fold‐increase over non‐stimulated. Data from three independent experiments were used in the analysis. n = 3, means ± SD are shown; two‐tailed unpaired Student's t‐test, *P 0.05, **P 0.01, ***P 0.001; ns, not significant.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "C Poly‐caspase activity in THEMIS KD 1G4‐CD8 cells. Cells were stimulated for 24 h with NY‐ESO‐1 pMHC tetramers. Camptothecin was used as a positive control for caspase activation. A FAM‐FLICA detection probe was used to assess poly‐caspase activity by flow cytometry. Data shown are a representative example of three independent experiments.D Quantification of poly‐caspase activity of cells from (C). Data from three independent experiments were used in the analysis. n = 3, means ± SEM are shown; two‐tailed unpaired Student's t‐test, *P 0.05, **P 0.01; ns, not significant.",
    "ncbi_link": "CD8: 925
THEMIS: 387357"
  },
  {
    "caption": "A Lentiviral KD of SHP1 expression in 1G4‐CD8 cells. KD efficiency was assessed using immunoblotting.",
    "ncbi_link": "CD8: 925"
  },
  {
    "caption": "B Annexin‐V staining of THEMIS and SHP1 KD 1G4‐CD8 cells. Control, THEMIS and SHP1 knock‐down Jurkat 1G4‐CD8 cells were stimulated for 24 h with plate‐bound 6V tetramers. Annexin‐V surface expression was analysed by flow cytometry and is shown as fold‐increase over non‐stimulated. Data from three independent experiments were used in the analysis. n = 3, means ± SD are shown; two‐way ANOVA, Bonferroni post‐test, *P 0.05, **P 0.01, ***P 0.001.",
    "ncbi_link": "CD8: 925
SHP1: 5777
THEMIS: 387357"
  },
  {
    "caption": "C Lentiviral knock‐down of THEMIS and SHP1 expression in primary humanCD4+T cells. Following transduction, cells were expanded on CD3/CD28 beads in the presence of exogenous IL‐2. Knock‐down efficiency was analysed by immunoblotting on day 4 post‐transduction.",
    "ncbi_link": "SHP1: 5777
THEMIS: 387357"
  },
  {
    "caption": "E Annexin‐V staining of 1G4‐CD8 cells re‐expressing a SHP1 tail tyrosine mutant. Jurkat 1G4‐CD8 cells were transduced with Knock‐down/re‐expression constructs for HA‐SHP1 wild‐type (wt) or Tyr536/564 to Phe double mutant (YYFF). Cells were stimulated and analysed by flow cytometry as in (B). Data shown are representative of three independent experiments. n = 3, means ± SD are shown.",
    "ncbi_link": "CD8: 925
SHP1: 5777"
  },
  {
    "caption": "A CD8+T cells from OT‐I Rag2−/−mice expressing wild‐type (LCK) or LCKS59A proteins were stimulated with H‐2Kb‐positive antigen‐presenting cells pulsed with serial dilutions of the OVA (257-264) peptide, the OVA peptide variants Q4 and T4, and VSV, a peptide that is not recognized by the OT‐I TCR. CD69 up‐regulation (left) and TCR down‐regulation (right) were analysed. Data are representative of three independent experiments.",
    "ncbi_link": "CD8: 12525
LCK: 16818
Rag2: 19374"
  },
  {
    "caption": "B CD8+T cells from OT‐I Rag2−/−mice expressing wild‐type (LCK) or LCKS59A proteins were labelled with CFSE and stimulated with serial dilution of H‐2Kb‐OVA or H‐2Kb‐Q4R7 peptide‐MHC tetramers. After 3 days, the absolute numbers of divided T cells were determined. Data are representative of three independent experiments.",
    "ncbi_link": "CD8: 12525
LCK: 16818
Rag2: 19374"
  },
  {
    "caption": "Sucrose gradient UV profile of 60S/40S/IAPV-IRES reaction mixture after an overnight run. The peaks corresponding to 80S and 40S were used for RNA extraction and UREA-PAGE shown in the inset.",
    "ncbi_link": "IRES: "
  },
  {
    "caption": "(D) Results of in vivo plasmid-to-plasmid transposition assay using WT or R848M RAG1 and the indicated forms of RAG2 containing or lacking (∆L) the four amino acids at the tip of the 333-342 loop, performed as described in (Zhang et al., 2019); (****, p<0.0001). Three biological replicates for each condition except in the last two columns where data from 11 biological replicates are presented.",
    "ncbi_link": "RAG1: 19373
RAG2: 19374"
  },
  {
    "caption": "(E) Results of in vivo plasmid-to-genome transposition assay using WT or R848M RAG1 and different forms of RAG2 as indicated. As previously demonstrated (Zhang et al., 2019), R848 (present in WT RAG1) and RAG2 acidic hinge residues 362-383 each potently suppress transposition. Substantial transposition is observed with the combination of RAG1 R848M and RAG2 1-361, which is further increased by ∆L; (***, p=0.001). Four biological replicates for each condition.",
    "ncbi_link": "RAG1: 19373
RAG2: 19374"
  },
  {
    "caption": "(F) In vivo recombination activity in HEK293T cells of mouse wild-type RAG1 or RAG1 R848M with RAG2 1-361 or 1-361 ∆L. (p=0.42 for wild-type RAG1 group, p=0.41 for RAG1 R848M group). Three biological replicates for each condition.",
    "ncbi_link": "RAG1: 19373
RAG2: 19374"
  },
  {
    "caption": "M-T LYVE1 staining of lymphatic vessels in the intestinal wall in adult mice. Genotypes and deletion lengths are indicated in (U).U Quantification of LYVE1 areas in (M-T). Length of the i∆Vegfc gene deletion is indicated in months (mo), and Vegfd indicates the VEGF-D genotype. Data are represented as mean ± SEM. Significant differences were determined using one-way ANOVA and Bonferroni post hoc analysis compared to WT intestine represented in (M). *P = 0.003, **P = 0.001, ***P = 0.0008, ♯P = 0.0002, §P = 0.0001.",
    "ncbi_link": "VEGF-D: 14205
Vegfd: 14205
Vegfc: 22341"
  },
  {
    "caption": "Overview of the small intestine cross section stained with nuclear red and highlighting the location of higher magnification images in (B-F); (I) for the entire villus and (II) for the villus base. β-Gal staining pattern of the villus in wild-type (Ctrl), Vegfc/LacZ (VC), Vegfr3/LacZ (VR-3), and Vegfr2/LacZ (VR-2) mice.Higher magnification images representing β-Gal staining of the villus base in Vegfc/LacZmice.Data information: Arrows indicate the VEGF-C expression in arterialSMC, arrowheads indicate the VEGF-C expression in SMCfibers in the villus, and asterisks highlight the VEGF-C expression in circular smooth muscle cell layer of the intestinal wall. Scale bars: 50 μm, except (C) inset 25 μm.",
    "ncbi_link": "LacZ: 
Vegfr3: 14257
Vegfr2: 16542
Vegfc: 22341"
  },
  {
    "caption": "Vegfc/LacZβ-Gal staining reaction with smooth muscle actin (SMA) peroxidase staining.Data information: Arrows indicate the VEGF-C expression in arterialSMC, arrowheads indicate the VEGF-C expression in SMCfibers in the villus, and asterisks highlight the VEGF-C expression in circular smooth muscle cell layer of the intestinal wall. Scale bars: 50 μm, except (C) inset 25 μm.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "Vegfc/LacZβ-Gal staining and LYVE1 peroxidase staining.Data information: Arrows indicate the VEGF-C expression in arterialSMC, arrowheads indicate the VEGF-C expression in SMCfibers in the villus, and asterisks highlight the VEGF-C expression in circular smooth muscle cell layer of the intestinal wall. Scale bars: 50 μm, except (C) inset 25 μm.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "Surface image of Vegfc/LacZβ-Gal-stained intestine (left) and cross section counterstaining with PECAM1 (right).Data information: Arrows indicate the VEGF-C expression in arterialSMC, arrowheads indicate the VEGF-C expression in SMCfibers in the villus, and asterisks highlight the VEGF-C expression in circular smooth muscle cell layer of the intestinal wall. Scale bars: 50 μm, except (C) inset 25 μm.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "Two-month-old mice received tamoxifen and were fed on high-fat diet (HFD) for seven weeks before analysis.Body weight change during seven weeks of HFD, expressed as average fold change in comparison with the starting weight. n = 16, WT; n = 6, Vegfd−/−; n = 16, VCiΔR26; n = 5, Vegfd−/−; VCiΔR26.Body weight comparisons at seven weeks of HFD. Significant differences were determined using one-way ANOVA and Bonferroni post hoc analysis compared to WT. *P = 0.004; **P = 0.003. n = 16, WT; n = 6, Vegfd−/−; n = 16, VCiΔR26; n = 5, Vegfd−/−; VCiΔR26.",
    "ncbi_link": "Vegfd: 14205"
  },
  {
    "caption": "H, I WT and lincRNA-EPS-/- iBMMs were infected with VSV (MOI 0.1) for 6 h or 10 h (H) or transfected with polyI:C (1 μg/mL) for 4 h or 8 h (I), phosphorylation and total protein expression were analyzed by Western blot with α-tubulin and β-Actin as loading controls.",
    "ncbi_link": "lincRNA-EPS: 102635290"
  },
  {
    "caption": "D 20 nM siRNA targeting negative control (NC) and PKR were transfected into iBMMs for 48 h, the protein and mRNA expression level of PKR were tested by RT-qPCR and Western blot, respectively.",
    "ncbi_link": "PKR: 19106"
  },
  {
    "caption": "H LincRNA-EPS was transcribed in vitro and pulled down proteins from iBMMs infected with VSV for 4 h, PKR protein was detected by Western blot and GAPDH was shown as a loading control.",
    "ncbi_link": "LincRNA-EPS: 102635290"
  },
  {
    "caption": "I RNA-pulldown using biotinylated lincRNA-EPS from cell lysates of polyI:C (1 and 2.5 μg/mL) transfected iBMMs for 4 h, PKR protein was detected by Western blot and β-Actin was shown as a loading control.",
    "ncbi_link": "lincRNA-EPS: 102635290"
  },
  {
    "caption": "A 20 nM siRNA for negative control (NC) and PKR were transfected into iBMMs following infected with VSV (MOI 0.1) for 4 h or 8 h, phosphorylation and total levels of STAT1, eIF2α and PKR were detected by Western blot and β-Actin was shown as a loading control.",
    "ncbi_link": "PKR: 19106"
  },
  {
    "caption": "B PKR was transfected into A549 cells for 24 h following stimulated with IFN-β (50 ng/mL) for 1 h to test STAT1 phosphorylation by Western blot and β-Actin was shown as a loading control.",
    "ncbi_link": "PKR: 8575"
  },
  {
    "caption": "C. Analysis of the association of MDGI mRNA expression with glioma patient survival using the GlioVis data portal. In the TCGA GBMLGG dataset (n = 667), patients with low MDGI expression (green line; n = 333, events = 101, median = 67,5) show significantly better survival than patients with high MDGI (red line; n = 334, events = 138, median = 41.5) expression (P = 2e-04). HR = 0.62 (0.48 - 0.8). The cumulative survival rates were estimated by using the Kaplan-Meier method.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "D. In glioblastoma samples, highest MDGI expression was observed in the mesenchymal subtype (M) compared to the classical (Cl) or pro-neural (PN) ones. However, it did not reach the statistical significance. GlioVis data portal, TCGA GBM dataset, n = 156. Pairwise t-test with corrections for multiple testing, p-values with Bonferroni correction.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "E. MDGI expression was high in the leading edge of the tumour (LE) and in infiltrating tumour cells (IT) in the IVY_Gap dataset (n = 122) where the gene expression profile in different anatomical structures of glioblastomas was analysed. LE, leading edge; IT, infiltrating tumour cells; CT, cellular tumour (cells within the tumour mass); PC, pseudopalisading cells; MP, microvascular proliferation. Numbers in the graph depict the P values: Pairwise t-test with corrections for multiple testing, p-values with Bonferroni correction.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "A, B Representative whole coronal section micrographs of murine brain injected with GFP (A) or MDGI-GFP (B) expressing U87MG glioma cells. Xenografted human cells were visualised by using anti-human vimentin (hVim) antibodies (red). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "G. Quantification of the number of U87MG secondary tumours (diameter >300 µm) detected in the whole brain (GFP: n = 5, MDGI-GFP: n = 9). Data are represented as mean ± SEM. **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "H. Quantification of the number of invasive U87MG cells that grew next to brain blood vessels (angiotropic co-opting tumour cells, diameter <300 µm) (GFP: n = 5, MDGI-GFP: n = 9). Data are represented as mean ± SEM. ****P < 0.0001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "I, J Representative micrographs of whole murine brain coronal sections injected with GFP (I) or GFP-MDGI (J) expressing LN229 glioma cells. Xenografted human cells were visualised by using anti-human vimentin (hVim) antibodies (red). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "O. Quantification of the number of invasive LN229 cells detected in the brain (GFP: n = 10, MDGI-GFP: n = 10). Data are represented as mean ± SEM. ****P < 0.0001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "P. Quantification of the number of invasive LN229 cells that grew next to brain blood vessels (angiotropic co-opting tumour cells, diameter <300 µm) detected in the brain (GFP: n = 10, MDGI-GFP: n = 10). Data are represented as mean ± SEM. Data are represented as mean ± SEM. ****P < 0.0001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "GFP: 
MDGI: 2170"
  },
  {
    "caption": "A. Transmitted light micrographs of MDGI-silenced (shMDGI1 and shMDGI2) and control (Scr) patient-derived BT12 and BT13 spheroids 11 days after gene silencing. Representative images of at least 3 independent experiments are shown. Scale bar: 200 μm.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "B. Methylcellulose assay demonstrating the ability for self-renewal of control (Scr) and MDGI-silenced (shMDGI1 and shMDGI2) patient-derived BT12 and BT13 cells after three weeks of culture. Representative images of at least 3 independent experiments are shown. Scale bar: 200 μm.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "C. Quantification of the colony size in methylcellulose of MDGI-silenced (sh1 and sh2) cells relative to the controls (Scr) that is set as 100 (n = 3). Data are represented as mean ± SD. ***P < 0.001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "D. MTT-proliferation assay of control (Scr) and MDGI-silenced (shMDGI1) BT12 and BT13 cells. The values of each cell line were normalized to the values at day 1 marked with a dashed line (n = 3). Data are represented as mean ± SD. ***P < 0.001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "E, F Representative whole coronal section micrographs of murine brain injected intracranially with control (BT12 Scr, n = 5) and MDGI-silenced (BT12 sh1, n = 5) BT12 cells. After four weeks animals were sacrificed, the brains were excised and prepared for immunohistochemistry. Control (Scr) cells grew very similarly to the parental BT12 cells forming a tumour mass with invasive tumour cells (single cell invasion) that eventually co-opted existing blood vessels (angiotropism) and formed secondary tumours (upper panels). No tumour growth was observed when MDGI-silenced cells were implanted (lower panels). Glioma cells were visualised by using anti-human vimentin (hVim red) and blood vessels using anti-podocalyxin antibodies (green). Nuclei were visualised by using DAPI (white). Scale bar: 1 mm (E) and 50 µm (F).",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "A. Binding of Annexin V Alexa Fluor 488 to control (Scr) and MDGI-silenced (shMDGI1) BT12 cells was measured by flow cytometric analyses five days after silencing. The analysis was performed by gating the cells into two populations: P1 (small, granular) and P2 (normal-sized cells) (30 000 analysed events/cell line, n = 3). B. Geometric mean fluorescence (FL-1) relative to the controls (Scr) that was set as 1 in P1 and P2 in MDGI-silenced (shMDGI1) cells. Data are represented as mean ± SD. *P < 0.05, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "E, F Representative micrographs of LGALS1-stained (green) BT12 control (E) and MDGI-silenced cells (F) six days after silencing. Nuclei were visualised by using DAPI (blue). Scale bar: 10 µm.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "G, H Representative micrographs of LGALS1-stained (green) BT13 control (G) and MDGI-silenced cells (H) six days after silencing. Nuclei were visualised by using DAPI (blue). Scale bar: 10 µm.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "I. Percentage of LGALS1-positive puncta staining in the control (Scr) and MDGI-silenced (sh1) cells. In total 0.4-1.2x104 LGALS1-stained cells were analysed from 50 mm2 coverslip areas (n = 6). Data are represented as mean ± SD. **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "J. Quantification of the percentage of dead cells six days after MDGI silencing and LGALS1 staining (n = 100) in control (Scr) and MDGI-silenced (sh1) BT12 and BT13 cells. Data are represented as mean ± SD. **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "K. Cytoplasmic cathepsin B activity in the control (Scr) and MDGI-silenced (sh1) BT12 and BT13 cells. Data are represented as mean ± SD. **P < 0.01; **P < 0.001, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "L. Number of live cells in MDGI-silenced BT12 and BT13 cells incubated without (sh1) or with (sh1+K777) the pan-cathepsin inhibitor (K777) after 1, 3 and 5 days of incubation. Data shows the percentage of live cells compared to the control (Scr) cells set as 100 %. Data are represented as mean ± SD. *P < 0.05; **P < 0.01, two-tailed, nonparametric Mann-Whitney's U-test.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "A. Proportions (mol %) of saturated (Sat), monounsaturated (Mono), diunsaturated (Di; total of 2 double bonds in the acyl chains), and polyunsaturated (Poly; total of 3-7 double bonds in the acyl chains) lipid species from the two main phospholipid classes (phosphatidylcholine PC and phosphatidylethanolamine PE) of the lysosomal fractions of the BT12 and BT13 control (Scr) and MDGI-silenced (shMDGI) cells. A representative graph of two independent experiments is shown.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "B. Fold change of the main PC and PE species in the lysosomal membranes of MDGI-silenced (shMDGI) and control (Scr) cells (Log2, by mol % data). Abbreviations: [Lipid class] [total number of acyl chain carbons]:[total number of double bonds in the chains]. A representative heatmap of two independent experiments is shown.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "C. Profiles of ceramide (Cer) species (mol %) in the lysosomal membranes of MDGI-silenced (shMDGI) and control (Scr) BT12 and BT13 cells. Abbreviations: Cer [number of acyl chain carbons]:[number of double bonds in the acyl chain]; all principal species containing a sphingosine chain. A representative graph of two independent experiments is shown.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "D. Ratio of the 24:1 to 24:0 (mol %.mol %) Cer species in the lysosomal membranes of MDGI-silenced (shMDGI) and control (Scr) BT12 and BT13 cells. A representative graph of two independent experiments is shown.",
    "ncbi_link": "MDGI: 2170"
  },
  {
    "caption": "Transversal section of a recombined VeCadCreER:Confetti AGM from an E10.5 embryo and immunostained with CD31 (C) (white in image, black in label) Multistack reconstruction of confocal images. Scale bars 30μm",
    "ncbi_link": "VeCad: 12562
Cre: 2777477
ER: 2099"
  },
  {
    "caption": "Transversal section of a recombined VeCadCreER:Confetti AGM from an E10.5 embryo and immunostained with Kit (D) (white in image, black in label). Multistack reconstruction of confocal images. Scale bars 20 μm",
    "ncbi_link": "VeCad: 12562
Cre: 2777477
ER: 2099"
  },
  {
    "caption": "Quantification and classification of IAHC containing recombined cells in TAM-induced VeCadCreER:Confetti embryos after IgG or αDll4 treatment. Embryos treated with αDll4 contain more IAHC with colored cells. Quantification of confocal images (n=7 embryos).",
    "ncbi_link": "VeCad: 12562
Cre: 2777477
ER: 2099"
  },
  {
    "caption": "Snapshots of Movie EV5. Time Lapse of embryonic organotypic slice from a CD41:YFP: H2B-GFP reporter mouse showing the recruitment of CD41:YFP negative cells (magenta central point-tracking analyses) migrating towards the IAHC (CD41:YFP+ cells). Green central point and relative tracking identify cells with non-directional movement. Scale bar: 5μm. Time expressed in hh:mm:ss.",
    "ncbi_link": "GFP: 
YFP: "
  },
  {
    "caption": "(A) Box-and-whiskers plot showing CSF p-tau235 concentrations in A-T- participants and across preclinical Alzheimer's disease (AD, dichotomised as A+T- and A+T+). CSF p-tau235 was increased already in A+T-, which represents the early cases within preclinical AD. A prominent increase was observed from A+T- to A+T+ cases, the latter representing late preclinical AD cases. Cut-off value for CSF p-tau235 positivity is displayed with black dashed line (19.92 pg/mL).",
    "ncbi_link": "tau235: 4137"
  },
  {
    "caption": "Trajectories of the different tau biomarkers in preclinical AD using a local weighted regression method (Loess curve). Changes on biomarkers levels in CSF are represented as z-scores using Aβ PET in centiloid scale (CL) as a proxy of disease progression. Abnormal biomarker levels were determined as two standard deviations (SD) above the mean. Incipient Aβ pathology positivity was determined as Aβ PET higher than CL 12 (Mila-Aloma et al., 2020). All samples were run in singlicates.",
    "ncbi_link": "Aβ: 351"
  },
  {
    "caption": "(c) qPCR analysis of mRNA levels of glycolytic enzyme genes in 5 dpci remote and wound border cardiac tissue (n = 2-3 technical replicates using pooled cDNA from 10 ventricles for each condition (n = 2 for pkmb and pdk4, and n = 3 for the other genes)).",
    "ncbi_link": "pdk4: 561007
pkmb: 445094"
  },
  {
    "caption": "(a Immunostaining of heart sections for PCNA and MEF2 in 5 dpci pkma2+/-; pkmb+/- and pkma2-/-; pkmb+/- animals; magnified view of area in white boxes shown below; arrowheads point to PCNA+ CMs; white dashed lines mark the wound border; percentage of PCNA+ CMs in the border zone shown on the right (n = 4-6 ventricles of each genotype).",
    "ncbi_link": "pkma2: 335817
pkmb: 445094"
  },
  {
    "caption": "Immunostaining of heart sections for N2.261 and MEF2 in 5 dpci pkma2+/-; pkmb+/- and pkma2-/-; pkmb+/- animals; magnified view of area in white boxes shown below; arrowheads point to N2.261+ CMs; white dashed lines mark the wound border; percentage of N2.261+ in the border zone shown on the right (n = 4-6 ventricles of each genotype).",
    "ncbi_link": "pkma2: 335817
pkmb: 445094"
  },
  {
    "caption": "Immunostaining of heart sections for PCNA and MEF2 in 5 dpci ppargc1a+/+ and ppargc1a-/- animals; magnified view of area in white boxes shown below; arrowheads point to PCNA+ CMs; white dashed lines mark the wound border; percentage of PCNA+ CMs in the border zone shown on the right (n = 4-6 ventricles of each genotype).",
    "ncbi_link": "ppargc1a: 553418"
  },
  {
    "caption": "d) Immunostaining of heart sections for N2.261 and MEF2 in 5 dpci ppargc1a+/+ and ppargc1a-/- animals; magnified view of area in white boxes shown below; arrowheads point to N2.261+ CMs; white dashed lines mark the wound border; percentage of N2.261+ CMs in the border zone shown on the right (n = 4-6 ventricles of each genotype).",
    "ncbi_link": "ppargc1a: 553418"
  },
  {
    "caption": "(e AFOG staining of heart sections from 60 dpci pkma2+/-; pkmb+/- and pkma2-/-; pkmb+/- animals; black dashed lines outline the scar area; scar area measured on the right (n = 3-5 ventricles of each genotype).",
    "ncbi_link": "pkma2: 335817
pkmb: 445094"
  },
  {
    "caption": "f) AFOG staining of heart sections from 45 dpci ppargc1a+/+ and ppargc1a-/- animals; black dashed lines outline the scar area; scar area measured on the right (n = 3-5 ventricles of each genotype).",
    "ncbi_link": "ppargc1a: 553418"
  },
  {
    "caption": "Immunostaining of heart sections for PCNA and MEF2 in 5 dpci animals (Tg(hsp70l:LOXP-STOP-LOXP-pdha1aSTA-T2A-mCherry) and Tg(hsp70l:LOXP-STOP-LOXP-pdk3b-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); magnified view of area in white boxes shown below; arrowheads point to PCNA+ CMs; white dashed lines mark the wound border; percentage of PCNA+ CMs in the border zone shown on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdha1a: 406702
pdk3b: 791206"
  },
  {
    "caption": "Immunostaining of heart sections for PCNA and MEF2 in 5 dpci animals (Tg(hsp70l:LOXP-STOP-LOXP-pdha1aSTA-T2A-mCherry) and Tg(hsp70l:LOXP-STOP-LOXP-pdk3b-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); magnified view of area in white boxes shown below; arrowheads point to PCNA+ CMs; white dashed lines mark the wound border; percentage of PCNA+ CMs in the border zone shown on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdha1a: 406702
pdk3b: 791206"
  },
  {
    "caption": "Immunostaining of heart sections for N2.261 and MEF2 in 5 dpci animals (Tg(hsp70l:LOXP-STOP-LOXP-pdha1aSTA-T2A-mCherry) and Tg(hsp70l:LOXP-STOP-LOXP-pdk3b-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); magnified view of area in white boxes shown below; arrowheads point to N2.261+ CMs; white dashed lines mark the wound border; percentage of N2.261+ CMs in the border zone shown on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdha1a: 406702
pdk3b: 791206"
  },
  {
    "caption": "Immunostaining of heart sections for N2.261 and MEF2 in 5 dpci animals (Tg(hsp70l:LOXP-STOP-LOXP-pdha1aSTA-T2A-mCherry) and Tg(hsp70l:LOXP-STOP-LOXP-pdk3b-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); magnified view of area in white boxes shown below; arrowheads point to N2.261+ CMs; white dashed lines mark the wound border; percentage of N2.261+ CMs in the border zone shown on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdha1a: 406702
pdk3b: 791206"
  },
  {
    "caption": "(f AFOG staining of heart sections from 60 dpci animals (Tg(hsp70l:LOXP-STOP-LOXP-pdha1aSTA-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); black dashed lines outline the scar area; scar area measured on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdha1a: 406702"
  },
  {
    "caption": "g) AFOG staining of heart sections from 60 dpci animals and Tg(hsp70l:LOXP-STOP-LOXP-pdk3b-T2A-mCherry) alone (control) or in combination with Tg(myl7:Cre-ERT2), all after tamoxifen and heat shock treatments); black dashed lines outline the scar area; scar area measured on the right (n = 4-5 ventricles of each genotype).",
    "ncbi_link": "mCherry: 
Cre: 2777477
hsp70l: 560210
myl7: 30592
pdk3b: 791206"
  },
  {
    "caption": "(a, b) Staining for Ki67, CTNI and DNA (DAPI) in control, PDHA1STA OE or PDK3 OE RNCMs cultured in growth (a) or non-growth (b) medium; arrowheads point to Ki67+ RNCMs; percentage of Ki67+ RNCMs shown on the right (n = 4 biological replicates for each condition).",
    "ncbi_link": "PDHA1: 18597
PDK3: 296849"
  },
  {
    "caption": "(c) Staining for CTNI and DNA (DAPI) in scratch assay using control, PDHA1STA OE or PDK3 OE RNCMs immediately or at 3 days after generating the scratch; magnified view of area in white boxes shown below; arrowheads point to membrane protrusions of RNCMs; quantification of CM membrane protrusions shown on the right (n = 4 biological replicates for each condition).",
    "ncbi_link": "PDHA1: 18597
PDK3: 296849"
  },
  {
    "caption": "(d) Reactome over-representation analysis of differentially regulated genes in PDK3 OE RNCMs compared to control.",
    "ncbi_link": "PDK3: 296849"
  },
  {
    "caption": "(e Heat map of gene expression for key regulators of cell cycle in PDK3 OE vs control RNCMs.",
    "ncbi_link": "PDK3: 296849"
  },
  {
    "caption": "f) Heat map of gene expression for key regulators of DNA replication in PDK3 OE vs control RNCMs.",
    "ncbi_link": "PDK3: 296849"
  },
  {
    "caption": "(J) The mRNA expression of IL-25, IL-33 and TSLP in islet grafts of mice with or without IL-33 treatment was examined by qPCR, and expressed relative to the control of each experiment. Data shown are the mean ± SEM (n=4-6 per group) and a one-way ANOVA was performed; **P<0.01, ***P<0.001.",
    "ncbi_link": "IL-25: 140806
IL-33: 77125
TSLP: 53603"
  },
  {
    "caption": "(A) ILC210 and non-ILC210 were isolated from ex vivo-expanded kidney ILC2 by flow sorting. ILC210 were transfected with control (ILC210-C) or IL-10 CRISPR-Cas9 (ILC210-IL-10). IL-10 was measured in culture supernatant of ILC210-C and ILC210-IL-10 via ELISA. Data shown are the mean ± SEM (n=6 per group) and an unpaired t-test was performed; ***P<0.001.",
    "ncbi_link": "CRISPR: 
Cas9: 57852564
IL-10: 16153"
  },
  {
    "caption": "(D) The mRNA expression of IL-10 in islet grafts at day 5 post islet transplantation was examined by qPCR. Data shown are the mean ± SEM (n=4 per group) and a one-way ANOVA was performed; **P<0.01, ***P<0.001.",
    "ncbi_link": "IL-10: 16153"
  },
  {
    "caption": "(G) Neutralizing anti-IL-10 antibodies or genetic ablation of IL-10 were used to block the effect of ILC210 on CD4+ T cells proliferation. Data shown are the mean ± SEM (n=6 per group) and an unpaired t-test was performed. ***P<0.001.",
    "ncbi_link": "IL-10: 16153"
  },
  {
    "caption": "A) Transcription levels of all M. florum coding sequences (CDS) quantified by RNA-seq. Transcription levels were calculated according to the number of fragments per kilobase per million of mapped reads (FPKM) observed over six replicates. The corresponding numbers of mRNA copies per cell, estimated from the measured M. florum RNA mass, are also indicated. CDS were sorted from least to most transcribed. The transcription level of selected genes of importance are presented. LDH, L-lactate dehydrogenase (peg.600/mfl596); G3PDH, glyceraldehyde-3-phosphate dehydrogenase (peg.583/mfl578); PGK, phosphoglycerate kinase (peg.582/mfl577); L24p and L7/L12, large subunit ribosomal proteins L24p (peg.133/mfl134) and L7/L12 (peg.605/mfl601); S7p, small subunit ribosomal protein S7p (peg.626/mfl623); RNAPβ, RNAPβ', and RNAPα, RNA polymerase subunits β, β', and α (peg.601/mfl597, peg.602/mfl598, and peg.149/mfl150); HPr, phosphotransferase system phosphocarrier protein HPr (peg.570/mfl565); σ70, RNA polymerase sigma factor RpoD (peg.269/mfl270).",
    "ncbi_link": "L24p: 2897678
large subunit ribosomal proteins L24p: 2897678
RNAPα: 2898191
G3PDH: 2898285
glyceraldehyde-3-phosphate dehydrogenase: 2898285
RNA polymerase sigma factor RpoD: 2898044
σ70: 2898044
HPr: 2897658
phosphotransferase system phosphocarrier protein HPr: 2897658
PGK: 2897801
phosphoglycerate kinase: 2897801
L-lactate dehydrogenase: 2897599
LDH: 2897599
RNA polymerase subunits β: 2897590
RNAPβ: 2897590
L7/L12: 2897798
RNAPβ': 2897589
S7p: 2897753
small subunit ribosomal protein S7p: 2897753"
  },
  {
    "caption": "(A) Blue-native gel electrophoresis and immunoblots of cells expressing the wild type form of Cor1 (Cor1WT), as well as the mutants Cor1N63A, N187A, D192A (Cor1*) and Cor1N63A, N187A, D192A, V189A, Y65A, L238A, K240A (Cor1**) in wild type (WT) background as well as in cells lacking CRD1 (crd1Δ). Blots were probed with antibodies against Cor1 to visualize Complex III (CIII), as well as Cox1, to monitor Complex IV (CIV). CV: Complex V; Cor1Cor2: multimer consisting of Cor1 and Cor2",
    "ncbi_link": "Cor1: 852235
CRD1: 851413
crd1: 851413"
  },
  {
    "caption": "(B) Reduced-minus-oxidized difference spectra of strains described in (A). Heme peaks are indicated for Cor1WT in WT background.",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "(A) Growth analysis of strains expressing the wild type form of Cor1 (Cor1WT) or the mutant Cor1N63A, N187A, D192A, V189A, Y65A, L238A, K240A (Cor1**). Growth curves and calculated doubling times from the exponential phase (insert) are presented. Cells were cultivated in media containing either glucose or glycerol as carbon source.",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "(D,E) Analysis of competitive fitness as described in (C). Cor1WT strains harbored a chromosomally-integrated hygromycin selection cassette, whereas Cor1** contained a clonNAT selection cassette (D). Subsequently, selection markers were switched as a control (E).",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "(A,B) Spectrophotometric measurement of Cyt c oxidase (CIV; A) and NADH Cyt c reductase (CIII; B) activities in solubilized mitochondrial extracts. Mitochondria were isolated from cells expressing the wild type form of Cor1 (Cor1WT) or the mutant Cor1N63A, N187A, D192A, V189A, Y65A, L238A, K240A (Cor1**).",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "(A) Polarographic measurement of KCN-sensitive oxygen consumption, driven by NADH in isolated coupled mitochondria. Mitochondria were isolated from cells expressing the wild type form of Cor1 (Cor1WT) or the mutant Cor1N63A, N187A, D192A, V189A, Y65A, L238A, K240A (Cor1**). Thereby, strains either overexpressed cytochrome c (Cyt cOE) or harbored the empty plasmid as a control (Empty). Measurement was performed in the absence (basal respiration) or presence (phosphorylating condition) of ADP.",
    "ncbi_link": "Cor1: 852235
Cyt c: 853507
cytochrome c: 853507"
  },
  {
    "caption": "Analysis of competitive fitness of strains described in (A). Cor1WT strains harbored a chromosomally-integrated clonNAT selection cassette, whereas Cor1** contained a hygromycin selection cassette. Strains were cultivated in CM media containing glucose (B) as carbon source.",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "Analysis of competitive fitness of strains described in (A). Cor1WT strains harbored a chromosomally-integrated clonNAT selection cassette, whereas Cor1** contained a hygromycin selection cassette. Strains were cultivated in CM media containing galactose (C) or glycerol (D) as carbon source.",
    "ncbi_link": "Cor1: 852235"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing.(A) PS1, PS2 and NCT were analyzed in cell lysates by immunoblotting using antibodies PS1N (PS1), BI-HF5C (PS2) and N1660 (NCT), respectively.(B) Full length APP and APP CTFs were analyzed by immunoblotting using antibody 6687. (C) Conditioned media were analyzed for secreted APPs by immunoblotting using antibody 22C11 and for total Aβ by combined immunoprecipitation/immunoblotting using antibodies 3552/2D8.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing. (D) Conditioned media were analyzed for individual Aβ species on Tris-Bicine urea SDS-PAGE by combined immunoprecipitation/immunoblotting of Aβ using antibodies 3552/2D8. Pooled clones of HEK293/sw cells stably transfected with PS1 L166P were used as reference. Note that more sample was loaded for the PS1 L435F mutant to facilitate analysis.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing. (E) PS1 expression levels were analyzed in cell lysates of HEK293/sw cells stably expressing PS1 WT or PS1 L435F by immunoblotting using antibodies PS1NT and 5E12, respectively.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing. (F) Conditioned media were analyzed by ELISA specific for Aβ40, Aβ42 and Aβ43. Data represent mean ± s.e.m. (n=6). Absolute levels and Aβ ratios are shown.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing.(G) Secreted Aβ was analyzed as in (D). To verify individual Aβ species, Aβ standards were co-migrated. Conditioned media were analyzed for individual Aβ species on Tris-Bicine urea SDS-PAGE by combined immunoprecipitation/immunoblotting of Aβ using antibodies 3552/2D8.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Pooled clones (A-D) and single cell clones (E-H) of HEK293/sw cells untransfected or stably transfected with the indicated WT and mutant PS1 constructs were analyzed for γ-secretase expression and APP processing.(H) Total Aβ in conditioned media was analyzed by MALDI-TOF MS following immunoprecipitation with antibody 4G8. Observed (Aβ42, 4513.6; Aβ43, 4615.3) and predicted molecular masses (Aβ42, 4514.1; Aβ43, 4615.2) were in good agreement.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "(A) PS1/2-/- MEF cells stably transduced with PS1 WT or PS1 L435F were analyzed for PS1 expression and APP processing by immunoblotting as in Fig 1A. Antibody 5E12 was used for the detection of the PS1 CTF.",
    "ncbi_link": "PS1: 19164
PS1: 5663"
  },
  {
    "caption": "(B) Stably transduced PS1/2-/- MEF cells of A were transiently transfected with APPsw-6myc and conditioned media were analyzed for Aβ species by Tris-Bicine urea SDS-PAGE. Individual Aβ species were verified by co-migration with Aβ standards (left panel) and quantified (right panel). Data represent mean ± s.e.m. of n=3 independently performed transfections. Note that more sample was loaded for the PS1 L435F mutant to facilitate immunoblot analysis.",
    "ncbi_link": "APP: 351
PS1: 5663
PS1: 19164"
  },
  {
    "caption": "(C) Secreted Aβ from cells in B were quantified by ELISA. Data represent mean ± s.e.m. of n=5 (PS1 WT) or 6 (PS1 L435F) independently performed transfections.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Immunohistochemical detection of Aβ40 (left column), Aβ42 (medium column) and Aβ43 (right column) in consecutive frontal cortex paraffin sections of two FAD cases with PS1 L435F mutation (cases #1 and #2, 1st and 2nd rows), another FAD case with different PS1 mutation (case #3, 3rd row) and one SAD case (case #4, forth row). In both PS1 L435F mutation cases the numerous Aβ plaques mainly contain Aβ42 and Aβ43 but less Aβ40. This is in contrast to Aβ plaques of the control FAD and SAD cases, in which solely Aβ42 predominates and Aβ43 is sparse; even levels of Aβ40 seem to be lower than in the PS1 L435F cases. Note that in both PS1 L435F cases several plaques are larger than those seen in cases #3 and #4, representing cotton wool plaques. Scale bar = 500 µm. Magnification is identical in all pictures.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "  HCT-116 cells were transfected with BIP or CHOP specific siRNAs for 48 h and then treated with or without 2mM sodium butyrate (NaB) for 24 h. Negative control (NC) scramble siRNA was used the negative control for the transfection. Representative Western blots are shown for BIP siRNA (A) and CHOP siRNA (C). The expression level of each protein was determined by densitometry and normalized to GAPDH (ratio of protein:GAPDH). (B) Normalized expression levels of BIP and LC3-II in HCT-116 cells treated with BIP specific siRNA. (C) Normalized expression levels of CHOP and LC3-II in HCT-116 cells treated with CHOP specific siRNA. Means and standard deviation (SD) of three independent experiments are shown. One-way ANOVA was used for statistical analysis. * P<0.05, ** p<0.01, compared to the respective control group.  ",
    "ncbi_link": "CHOP: 1649
BIP: 64374"
  },
  {
    "caption": "HA immunoprecipitation of stably expressed ZNF282-HA in cells previously transfected with ΔDUF3669-ZNF398-GFP and WT-ZNF398-GFP followed by detection of ZNF398 constructs in the IPs through Western-Blot using an anti-GFP antibody. Bottom: Western-Blot using an anti-HA antibody on the IPs. Input = Cellular lysate, IP = Immunoprecipitate",
    "ncbi_link": "GFP: 
ZNF398: 57541"
  },
  {
    "caption": "Left: DUF3669-only and KRAB domain constructs used. Right: HA immunoprecipitation in cells previously co-transfected with ZNF398-DUF3669-HA and either ZNF282-KRAB-Flag or ZNF282-DUF3669-Flag followed by detection of either of these protein constructs in the IPs through Western-Blot using an anti-Flag antibody. Bottom: Western-Blot using an anti-HA antibody on the IPs.",
    "ncbi_link": "Flag: 
HA: 
ZNF282: 8427
ZNF398: 57541"
  },
  {
    "caption": "Immunoprecipitations of HA-tagged KRAB domains in order to check\u2028 interaction with cKAP1. Co-transfection of Flag-tagged cKAP1 (upper panel) or Flag-tagged hKAP1 (lower panel) and HA-tagged ZNF398 DUF3669 domain negative control, H2ZYM4 and M3XKG1 cKRAB domains and ZNF93 hKRAB domain in KAP1 KO HAP1 cells followed by HA-immunoprecipitation. cKAP1 and hKAP1 presence was revealed by Western-Blot using an anti-Flag antibody. Input = Cellular lysate, IP = Immunoprecipitate. Western-Blot using an HA antibody on the IPs at the bottom.",
    "ncbi_link": "Flag: 
HA: 
cKAP1: 102365962
hKAP1: 10155
KAP1: 10155
ZNF398: 57541
ZNF93: 81931"
  },
  {
    "caption": "Quantification of α-MHC transcript abundance N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "ncbi_link": "α-MHC: 17888"
  },
  {
    "caption": "Quantification of β-MHC transcript abundance N=4 to 18 mice/group, all 6 weeks after TAC or sham surgery.",
    "ncbi_link": "β-MHC: 140781"
  },
  {
    "caption": "(P) Western blot analysis for TIP30 and GAPDH in hearts from TIP30 wild-type (WT) and heterozygous (Het) after AAV-TropT-TIP30 or AAV-Control (AAV-Con) injection followed by 6 weeks of TAC surgery.",
    "ncbi_link": "TIP30: 53415
TropT: 21956"
  },
  {
    "caption": "Quantification of HW/TL ratio (Q) ratio in AAV-Con or AAV-TropT-TIP30 treated Tip30 heterozygous (Het) or WT mice 6 weeks after TAC or sham surgery (N=5 to 11 mice/group).",
    "ncbi_link": "TropT: 
Tip30: 53415
TIP30: 53415"
  },
  {
    "caption": "Quantification of LuW/TL (R) ratio in AAV-Con or AAV-TropT-TIP30 treated Tip30 heterozygous (Het) or WT mice 6 weeks after TAC or sham surgery (N=5 to 11 mice/group).",
    "ncbi_link": "TropT: 
Tip30: 53415
TIP30: 53415"
  },
  {
    "caption": "(A) Western blot for TIP30 and GAPDH in neonatal rat cardiomyocytes (NRCM) after adenoviral transduction with Ad.Control (Ad.Con) or Ad.TIP30.",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "Quantification of cardiomyocyte area (B), N=6 to 8 samples/group in NRCM transduced with Ad.Con or Ad.TIP30 and stimulated as indicated. ET-1: endothelin-1, FBS: fetal bovine serum, PE: phenylephrine.",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "Quantification of protein/DNA ratio (C), N=9 samples/group in NRCM transduced with Ad.Con or Ad.TIP30 and stimulated as indicated. PE: phenylephrine.",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "Quantification of Acta1 mRNA transcript abundance (D), N=3 samples/group in NRCM transduced with Ad.Con or Ad.TIP30 and stimulated as indicated. ET-1: endothelin-1 PE: phenylephrine.",
    "ncbi_link": "Acta1: 29437
TIP30: 292935"
  },
  {
    "caption": "Quantification of cell death with a 7-AAD assay (E), N=7 samples/group in NRCM transduced with Ad.Con or Ad.TIP30 and stimulated as indicated. PE: phenylephrine.",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "(G) Western blot for TIP30 and Actin in mouse hearts with AAV9 mediated overexpression of TIP30 (AAV-TIP30) or from mice treated with a control AAV9 construct (AAV-Con) followed by 2 weeks of TAC surgery.",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "Quantification of HW/TL ratio (H), N=8 to 13 mice/group 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice. *",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "Quantification of cardiomyocyte area (I), N=4 to 5 mice/group 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice.",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "(J) Serial echocardiography with quantification of echocardiographic fractional area change 2, 4 and 6 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice (N=10 to 14 mice/group and time point).",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "(B) Western blot analysis of co-immunoprecipitation (IP) from HEK cells transfected with GST-TIP30 and eEF1A1-Myc.",
    "ncbi_link": "GST: 
Myc: 
eEF1A1: 171361
TIP30: 292935"
  },
  {
    "caption": "Western blot analysis of GST-pulldown assays with GST or GST-tagged eEF1A1 (GST-eEF1A1) and TIP30-His full length protein (TIP30-His) and TIP30 deletion mutants ΔN25 (TIP30-ΔN25-His), ΔN52 (TIP30-ΔN52-His), ΔC15 (TIP30-ΔC15-His) and Δ102-107 (TIP30-ΔN102-104-His, G)",
    "ncbi_link": "His: 
TIP30: 292935"
  },
  {
    "caption": "(J) Quantitative Real-Time PCR analysis of eEF1A1 and eEF1A2 mRNA abundance in hearts from neonatal mice, adult wild-type mice (Adult) and adult wild-type mice 2 weeks after TAC surgery (Adult TAC, N=3 to 4 mice/group). *P<0.05, ***P<0.001. One-way ANOVA with Sidak´s multiple comparisons test.",
    "ncbi_link": "eEF1A1: 13627
eEF1A2: 13628"
  },
  {
    "caption": "(B) Western blot analysis of anti-Myc immunoprecipitation (IP) in NRCM co-transduced with Ad.eEF1A1-Myc and either control virus (Ad.con) or Ad.TIP30. Endogenous eEF1B2 was detected. The IP input for eEF1B2, eEF1A1-myc and TIP30 is shown below. (C) Quantification of eEF1B2 abundance after eEF1A1-myc IP under conditions shown in (B) ",
    "ncbi_link": "Myc: 
eEF1A1: 171361
TIP30: 292935"
  },
  {
    "caption": "(D) Microscopy images of NRCM after adenoviral transduction with Ad.TIP30 or control virus (Ad.Con) and stimulation with phenylephrine (PE) and subsequent Proximity Ligation Assay (PLA). Red: eEF1A1-eEF1B2 interaction; Blue: DAPI. (scale bar: 50µm). (E) Quantification of eEF1A1-eEF1B2 interaction in conditions described in (D) ",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "Western blot analysis for TIP30, eEF1A1 and GAPDH in C57BL/6 WT mice 3 days (A, B), N=4 mice/group, 2 weeks (C, D), N=4 to 8 mice/group and 6 weeks (E, F), N=4 to 8 mice/group after TAC or sham surgery and their quantification. KO denotes TIP30 homozygous knock-out.",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "(G, H) Western blot for TIP30, eEF1A1 and Actin in TIP30 Het mice 6 after TAC surgery and their quantification (N=4 mice/group).",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "(I, J) Western blot for TIP30, eEF1A1 and Actin 2 weeks after sham or TAC surgery in AAV-Con or AAV-TIP30 treated C57BL/6 WT mice and their quantification (N=4 mice/group). A ratio of TIP30 and eEF1A1 expression was calculated for each condition.",
    "ncbi_link": "TIP30: 53415"
  },
  {
    "caption": "Quantification of Tip30 and eEF1A1 mRNA transcript abundance in human failing hearts (A), N=6 to 8 hearts/group A ratio of Tip30 and eEF1A1 expression was calculated",
    "ncbi_link": "eEF1A1: 1915
Tip30: 10553"
  },
  {
    "caption": "Quantification of Tip30 and eEF1A1 mRNA transcript abundance in patients with Hypertrophic Cardiomyopathy (HCM; B, N=4 to 8 hearts/group) A ratio of Tip30 and eEF1A1 expression was calculated",
    "ncbi_link": "eEF1A1: 1915
Tip30: 10553"
  },
  {
    "caption": "Quantification of Tip30 and eEF1A1 mRNA transcript abundance in 6 months old mdx mice or WT mice (C), N=4 mice/group. A ratio of Tip30 and eEF1A1 expression was calculated",
    "ncbi_link": "mdx: 13405
eEF1A1: 13627
Tip30: 53415"
  },
  {
    "caption": "(E) Echocardiographic diastolic left-ventricular wall-thickness in MDX mice at the age of 2 months at baseline, and 1-9 months (mo) after injection of AAV9-Con or AAV9-TIP30 (TIP; N=6 to 7 mice/group).",
    "ncbi_link": "MDX: 13405
TIP: 53415
TIP30: 53415"
  },
  {
    "caption": "(F) Quantification of HW/TL ratio of 9mo old MDX mice, N=5 to 6 mice/group.",
    "ncbi_link": "MDX: 13405"
  },
  {
    "caption": "(A) Western blot analysis of isolated neonatal rat cardiomyocytes (NRCM) after adenoviral transduction either with control adenovirus (Con) or Ad.TIP30 (TIP30) followed by stimulation with phenylephrine (PE, for 3 hours) and puromycin incorporation (for 30 min). (B) Quantification of the Western blot shown in (A) (N=3 samples/group). ",
    "ncbi_link": "TIP30: 292935"
  },
  {
    "caption": "(C) Quantification of cell surface area of isolated neonatal mouse cardiomyocyte of Tip30 Het and WT mice treated with endothelin-1 (ET-1) and Narciclasine (Narci) or without stimulation as indicated (N=6 samples/group).",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "Quantification of HW/TL ratio (E), N=6 to 10 mice/group, in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "Quantification of , echocardiographic wall thickness (F), N=6 to 10 mice/group, in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "Quantification of cardiomyocyte area (G), N=5 mice/group in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "Quantification of fractional area change (FAC, H, N=6 to 10 mice/group) in Tip30 Het or WT mice 2 weeks after TAC. Animals were treated with Narciclasine daily for 14 days after TAC as indicated.",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "(I) Western blot analysis of puromycin incorporation in hearts of Tip30 Het and WT mice 3 days after TAC or sham surgery and daily Narciclasine (Narci) injection and their quantification (N=2 to 4 mice/group). Puromycin was injected 3 hours prior to sacrifice.",
    "ncbi_link": "Tip30: 53415"
  },
  {
    "caption": "(D) mIMCD-3 cells stably expressing cilia-bPAC  or cyto-bPAC, cultured in a 3D matrix in the dark, during light  exposure (1 h light/1 h dark, 9 days, 465 nm, 38.8 µW/cm²) or in the dark  and incubated with 10 µM of Forskolin. Exemplary images are shown (n > 3). (E) Quantification of the data exemplified in (D). Data are shown as mean ± S.D., each datapoint corresponds to an independent experiment; p values calculated using an unpaired, two-sided Student's t-test are indicated.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(D) Immunoblotting  of lysates from mIMCD-3 wild-type (WT) cells and mIMCD-3  cells stably expressing cilia-bPAC  for S6 ribosomal protein (S6RP) phosphorylation  at  Ser235/236 (pS6RP). Levels of total S6RP  protein (S6RP) and beta-Tubulin  have been determined as controls. Cilia-bPAC  cells were treated with DMSO  (control) or with 10 nM of Rapamycin. All cells were stimulated with light (1 h light/1 h dark, 48 h, 465 nm, 38.8 µW/cm²) (E) Quantification of the pS6RP/S6RP  ratio. Data are shown as mean ± S.D., n > 3; p values were calculated using a paired, two-sided Student's t-test. Each data point shows an independent experiment",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(G) mIMCD-3 cells stably expressing cilia-bPAC, cultured in a 3D matrix in the dark, during light  exposure (1 h light/1 h dark, 9 days, 465 nm, 38.8 µW/cm²) and incubation with 10 nM rapamycin. Light  exposure started 2 d later than incubation with 10 nM rapamycin. Exemplary images are shown (n = 3) (H) Quantification of the data exemplified in (G). Data are shown as mean ± S.D., each datapoint corresponds to an independent experiment; p values calculated using a paired, two-sided Student's t-test are indicated",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(A)  mIMCD-3  cells stably expressing cilia-bPAC, cultured in a 3D matrix in the dark  or during light  exposure (1 h light/1 h dark, 9 days, 465 nm, 38.8 µW/cm²) and incubated with DMSO  (control), 250 µM IBMX, a ubiquitous PDE inhibitor, or 10 µM Rolipram, a PDE4-specific inhibitor. Exemplary images are shown (n = 3). Scale bars are indicated. (B) Quantification of data exemplified in (A). Data are shown as mean ± S.D., p values calculated using an unpaired, two-sided Student's t-test are indicated. Data points show individual experiments.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(C)  mIMCD-3  cells stably expressing cyto-bPAC, cultured in a 3D matrix during light  exposure (1 h light/1 h dark, 9 days, 465 nm, 38.8 µW/cm², 1 day after pharmacological stimulus) and incubation with DMSO  or 10 µM rolipram. Exemplary images are shown (n = 4-5). Scale bars are indicated. (D) Quantification of data exemplified in (C) Data are shown as mean ± S.D., p values calculated using an unpaired Student's t-test are indicated. Data points show individual experiments.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(H)  mIMCD-3 cells stably expressing cilia-bPAC, cultured in a 3D matrix during light  exposure (1 h light/1 h dark, 9 days, 465 nm, 38.8 µW/cm², 1 day after pharmacological stimulus) and incubation with DMSO  (0 µM), 3 µM, or 10 µM of the Pde4-long-isoform activator MR-L8. Exemplary images are shown (n = 3). Scale bars are indicated. (I) Quantification of data exemplified in (H). Data are shown as mean ± S.D., p values calculated using a paired, two-sided Student's t-test are indicated. Data have been normalized to the Light, 0 µM  MR-L8 condition (Set to 100%) within each experiment. Data points show individual experiments.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(I) 3D culture of mIMCD-3 cells stably expressing cilia-bPAC, incubated with DMSO  (control) or the EP4-inhibitor L161,982 in the dark  or during light  exposure (1 light/1 h dark, 9 days, 465 nm, 38.8 µW/cm², started 2 d after pre-incubation with DMSO  or L161,982). Exemplary images are shown (n = 3). (J) Quantification of images exemplified in (I). Data are shown as mean ± S.D., p values calculated using a paired, two-sided Student's t-test are indicated. Data points show individual experiments and have been normalized to the light/DMSO  condition (Set to 100%) within each experiment.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(F) 3D culture of mIMCD-3 cells stably expressing cilia-bPAC, incubated with DMSO  (control) or 20 µM Celecoxib, a COX-2-inhibitor, in the dark  or during light  exposure (1 light/1 h dark, 9 days, 465 nm, 38.8 µW/cm², started 2 d after pre-incubation with DMSO  or Celecoxib). Exemplary images are shown (n = 3). Scale bars are indicated. (G) Quantification of images exemplified in (F) and from 3D cultures incubated with 1 μM celecoxib. Data are shown as mean ± S.D., p values calculated using a paired, two-sided Student's t-test are indicated. Data points show individual experiments.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(A) Wild-type (WT), cilia-bPAC, or cyto-bPAC  (magenta)  mIMCD-3  cells were stimulated by light  (for 1 h prior to fixation, 465 nm, 38.8 µW/cm²), and treated with DMSO  (control) or 50 µM Ciliobrevin-D, a dynein-inhibitor. Cells were labeled with DAPI  (blue) to label the DNA, an ARL13B  antibody (white) to label cilia, and a phospho-specific (Ser133) CREB  antibody (pCREB, green). Arrows indicate the direction and the length of the shift of the respective fluorescence channel. The box indicates the position of the magnified view shown on the right of each panel. B) Quantification of the ciliary  pCREB signal in cilia-bPAC and cyto-bPAC  cells. Data are shown as mean ± S.D., n > 3. Each data point represents an independent experiment and corresponds to the median of > 73 cilia  (biological replicates); p values for an unpaired, two-sided Student's t-test with Welch's correction are indicated.",
    "ncbi_link": "bPAC: "
  },
  {
    "caption": "(C) mIMCD-3 Ift27-/- cells with or without stable cilia-bPAC  expression (magenta) were stimulated with light  (for 1 h prior to fixation, 465 nm, 38.8 µW/cm²). Cells were labeled with DAPI  (blue) to label the DNA, an ARL13B  antibody (white) to label cilia, and a phospho-specific (Ser133) CREB  antibody (pCREB, green). Arrows indicate the direction and the length of the shift of the respective fluorescence channel. The box indicates the position of the magnified view shown on the right of each panel. (D) Quantification of the ciliary  pCREB  signal. Data are shown as mean ± S.D., n > 3. Each data point represents the median of > 90 cilia  from the same experiment; p values are indicated for an unpaired, two-sided Student's t-test with Welch's correction.",
    "ncbi_link": "bPAC: 
Ift27: 67042"
  },
  {
    "caption": "(A-C) Tissue lysates from (A) spleen, (B) liver  and (C) kidney  from 6- to 9-day old indicated mice  were immunoblotted  to determine cleavage of  caspase-1. Each lane represents a lysate from a different mouse. Positive control lanes (+) are BMDMs  stimulated with LPS/ATP; negative control lanes (-) are respective organ homogenates from caspase-1-/- mice.",
    "ncbi_link": "caspase-1: 12362"
  },
  {
    "caption": "(D-G) Tissue lysates from (D, F) spleen  and (E, G) liver  from 6- to 9-day old indicated mice  were immunoblotted  to determine pro-IL-1β cleavage to  IL-1β (D-E) or GSDMD  cleavage to its p30   and p20  fragments (F-G). Each lane represents a lysate from a different mouse. Positive control lanes (+) are BMDMs  stimulated with LPS/ATP; negative control lanes (-) are respective organ homogenates from (D-E) caspase-1-/- or (F-G) Gsdmd-/- mice.",
    "ncbi_link": "caspase-1: 12362
Gsdmd: 69146"
  },
  {
    "caption": "Genotypes are indicated as WT for S100a4cre-/- x Fstl1flox+/flox+ mice and cfKO for S100a4cre+/- x Fstl1flox+/flox+. (A) S100a4 expression is induced in the ischemic area (IA). qPCR analysis of mRNA expression of S100a4 in ischemic heart and sham operated heart of WT mice and cfKO mice. Heart samples were harvested at 7 days after the surgery. Statistical analysis was performed by two-way ANOVA. Post Hoc test was performed by Tukey test. Error bars represent mean ± SEM (n=16 and 15 for WT and cfKO sham group, n=15 and 14 for WT and cfKO MI group, respectively).",
    "ncbi_link": "Fstl1: 14314
S100a4: 20198"
  },
  {
    "caption": "Genotypes are indicated as WT for S100a4cre-/- x Fstl1flox+/flox+ mice and cfKO for S100a4cre+/- x Fstl1flox+/flox+. (B) qPCR analysis of mRNA expression of Fstl1 and Tgfβ1 in sham and post-MI heart. Error bars represent mean ± SEM (n=16 and 15 for WT and cfKO sham group, n=15 and 14 for WT and cfKO MI group, respectively). Statistical analysis was performed by two-way ANOVA. Post Hoc test was performed by Tukey test.",
    "ncbi_link": "Fstl1: 14314
S100a4: 20198
Tgfβ1: 21803"
  },
  {
    "caption": "Genotypes are indicated as WT for S100a4cre-/- x Fstl1flox+/flox+ mice and cfKO for S100a4cre+/- x Fstl1flox+/flox+. (C) Western blot analysis of Fstl1 protein expression in ischemic and sham-operated hearts at day 7 after the surgery. Quantified values of Fstl1 protein in WT and cfKO mouse hearts normalized by GAPDH band intensity are shown. Statistical analysis was performed by two-way ANOVA. Post Hoc test was performed by Tukey test. Error bars represent mean ± SEM (n=5 for each sham group and n=6 for each MI group).",
    "ncbi_link": "Fstl1: 14314
S100a4: 20198"
  },
  {
    "caption": "Genotypes are indicated as WT for S100a4cre-/- x Fstl1flox+/flox+ mice and cfKO for S100a4cre+/- x Fstl1flox+/flox+. (D) Fstl1 protein expression in isolated cardiac fibroblasts from cfKO and littermate WT neonatal mice. Cell lysate and its media from cells cultured for 24 hours without FBS were assessed by western blotting. Error bars represent mean ± SEM (n=3 per group). Statistical analysis was performed by unpaired t-test (2-tailed). The experiments were performed twice independently.",
    "ncbi_link": "Fstl1: 14314
S100a4: 20198"
  },
  {
    "caption": "(A) Mouse survival curve after MI and sham surgery. The mortality of the WT and Fstl1-cfKO mice after MI surgery was 27.1% and 46.7%, respectively. Log-rank (Mantel-Cox) test was used for statistical analysis (n=16 for WT sham, n=15 for Fstl1-cfKO sham, n=59 for WT MI and n=30 for Fstl1-cfKO MI).",
    "ncbi_link": "Fstl1: 14314"
  },
  {
    "caption": "(A) Transcript mRNA expression of Col1a1 and Fn1 in sham and post-MI hearts. Hearts were obtained at day 7 after surgery. Error bars represent mean ± SEM (n=13-16 for each group). Statistical analysis was performed by two-way ANOVA. Post Hoc test was performed by Tukey test.",
    "ncbi_link": "Col1a1: 12842
Fn1: 14268"
  },
  {
    "caption": "(C) Transcript level of Fstl1, S100a4 and Acta2 mRNA in NRCFbs was determined by qPCR analysis. The samples were harvested at 24 hours after stimulation with recombinant TGF-β1 (10ng/ml) or control vehicle. Error bars represent mean ± SEM (Fstl1 and S100a4: n=6 for each group, Acta2: n=3 for each group). Statistical analysis was performed by unpaired t-test (2-tailed) for Fstl1 and S100a4, and non-parametric unpaired t-test (2-tailed) for Acta2. Two independent experiments were performed.",
    "ncbi_link": "Acta2: 81633
Fstl1: 79210
S100a4: 24615"
  },
  {
    "caption": "(C) Representative images of NRCFbs scratch assay (left) and quantified cell migration (right). NRCFbs were transfected by Fstl1 siRNA or siRNA non-targeting negative control for 12 hours followed by culturing in 0.5% FBS media for 24 hours. The confluent cell sheet was scratched and cell migration was assessed at 6 hours after the scratch. Scale bar indicates 100µm. Error bars represent mean ± SEM (n=10 for each group). Statistical analysis was performed by unpaired t-test (2-tailed). Two independent experiments were performed.",
    "ncbi_link": "Fstl1: 79210"
  },
  {
    "caption": "(D) Fstl1-stimulation of cell migration was reversed by PD98059. Endogenous Fstl1 in NRCFbs was ablated by Fstl1 siRNA. Serum-deprived NRCFbs were treated with PD98059 (5nM) for 30 min and then stimulated by Fstl1 (50ng/ml) or vehicle. Cell migration was assessed at 6 hours after Fstl1 stimulation. Error bars represent mean ± SEM (n=7-9 for each group). Statistical analysis was performed by Kruskal-Wallis test and Dunnett's T3 test. Two independent experiments were performed.",
    "ncbi_link": "Fstl1: 79210"
  },
  {
    "caption": "(A, B) Fibroblast proliferation was assessed by Edu incorporation assay. Endogenous Fstl1 was ablated by siRNA. NRCFbs were cultured in 0.5% FBS condition for 48 hours to synchronize the cell cycle. EdU (10μM as the final concentration) was added into media at 4 hours before harvest. Error bars represent mean ± SEM (n=5, each group). Statistical analysis was performed by unpaired t-test (2-tailed). Two independent experiments were performed. (B) Effect of exogenous Fstl1 on cardiac fibroblast proliferation. Cells were cultured in FBS 0.5% media for 24 hours. Recombinant Fstl1 (50ng/ml) or vehicle were added to 2% FBS-containing media and cultured for 48 hours. EdU was added into media at 4 hours before harvest. Error bars represent mean ± SEM (n=7, each group). Statistical analysis was performed by unpaired t-test (2-tailed). Two independent experiments were performed.",
    "ncbi_link": "Fstl1: 79210"
  },
  {
    "caption": "C. MCF7 cells were treated with Tam for 6 h and total RNA was prepared and cDNAs were analyzed by RT-QPCR with specific primers for GREB1. The values were normalized against 28S mRNA and represent the ± SEM of three experiments.",
    "ncbi_link": "28S: 
GREB1: 9687"
  },
  {
    "caption": "F Minimal inhibitory concentrations of DHA treated wild-type, heterozygous (YME1/yme1) and homozygous (yme1/yme1) mutant strains. Plates were imaged after 72h.",
    "ncbi_link": "YME1: 856135
yme1: 856135"
  },
  {
    "caption": "D Competitive growth assay of DHA resistant single cell clones. Wild-type (mCherry+_Cre_Puro) and knockout (GFP+_Puro) sister clones were derived from mutant (retrovirus - intron RE, darker shading, Tol2 transposon - intron T2, lighter shading) resistant colonies, treated with DHA, analyzed with flow cytometry and Sanger sequenced for insertion site mapping.",
    "ncbi_link": "GFP: 
mCherry: 
Cre: 2777477"
  },
  {
    "caption": "C, D (C) Fluorescence and (D) brightfield images of DMSO (control), 5-ALA (0.0625mM), DHA (1μM), or 5-ALA and DHA (0.0625mM and 1μM) treated tumor organoids (CNS-PNET-like, c-MYC overexpression). Organoids were imaged on day 1, day 5 and day 7. One experiment is shown, representative of four independent experiments.",
    "ncbi_link": "c-MYC: 4609"
  },
  {
    "caption": "(a) Immunofluorescence labeling of wildtype  mouse dorsal skin samples (Dnmt1f/f, skin from P3) shows  expression  of DNMT1 throughout epidermal layers  whereas keratinocyte-specific knockout (Dnmt1Δ/Δep) results in the almost absence of a specific staining in the epidermis  and in hair follicles. Dashed lines indicate the dermal-epidermal border and dotted lines indicate hair follicles.",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(d) Knockout of Dnmt1 results in lower levels of DNA methylation in the epidermis and in hair follicles as determined by anti 5-mC labeling of P3 skin. Dashed lines indicate the dermal-epidermal border and dotted lines indicate hair follicles.",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(h) Hematoxylin and Eosin (H&E) staining, immunolabeling  for KERATIN 10 (KRT10), LORICRIN (LOR) and KERATIN 6 (KRT6) expression of dorsal skin sections (P5) of control and Dnmt1Δ/Δep mice.",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(c) Flow cytometric analysis of the respective immune cell  populations from the epidermis  of control and Dnmt1Δ/Δep mice  of different postnatal age. Cells are shown as  percent of  viable  cells. Data are mean ± SEM, two-tailed t-test. ns, not significant, * p≤0.05, ** p≤0.01, **** p≤0.0001, n=3 (P3), 4 (P5) and 4 (P6 + P7). Data information: Scale bars, 50 µm.",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(d) Relative mRNA expression levels of immune related genes in control and Dnmt1Δ/Δep mice at P3 (n=3), P5 (n=5) and P7 (n≥3). Data are mean ± SEM. P values are calculated using one-way ANOVA with post hoc Tukey multiple comparison test, * p≤0.05, ** p≤0.01, *** p≤0.001 , **** p≤0.0001. Data information: Scale bars, 50 µm.",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(a) Relative mRNA expression levels of epidermal Intracisternal A-type particle  (IAP) during different postnatal time points (P0 n≥3, P3 n=3, P5 n=5, P7 n≥3  mice), which were compared using one way-ANOVA with post hoc Tukey multiple comparison test. Data are mean ± SEM. ns not significant, * p≤0.05, ** p≤0.01.",
    "ncbi_link": "IAP: 11797///11796///11799
Intracisternal A-type particle: 11797///11796///11799"
  },
  {
    "caption": "(c) Relative expression  of immune related genes of the  epidermis from P7 of control (n≥7), Dnmt1Δ/Δep, (n≥8), MAVS knockout (Mavs-/-, n=7) and Dnmt1Δ/Δep Mavs-/- (n=6) mice were compared using one way-ANOVA with post hoc Holm-Sidak multiple comparison test. Data are mean ± SEM. ns not significant, * p≤0.05, ** p≤0.01, *** p≤0.001, **** p≤0.0001.",
    "ncbi_link": "Dnmt1: 13433
MAVS: 228607
Mavs: 228607"
  },
  {
    "caption": "Immortalized  human keratinocytes (NHEK  SV-Tert3-5) were treated with 5-aza-2′-deoxycytidine (DAC) or vehicle (PBS). (c, d) PicoGreen staining of PBS- and DAC-treated keratinocytes for 48h detected micronuclei  (arrow), which were analyzed in a blinded manner, and compared using two-tailed t-test. Data are mean ± SEM, * p≤0.05 (n=3 biological replicates) (d). Data information: Scale bars, 20 µm",
    "ncbi_link": "Tert: 7015"
  },
  {
    "caption": "Immortalized human keratinocytes (NHEK SV-Tert3-5) were treated with 5-aza-2′-deoxycytidine (DAC) or vehicle (PBS). (e) Co-labeling of  DNA by PicoGreen and by  cGAS  in  PBS and DAC  treated  keratinocytes. Within enlarged sections on the right arrows point at  DNA/cGAS double-positive blebs and micronuclei. (f) Relative expression of CCL5 and IFT2 in keratinocytes treated with PBS or DAC  for 45 h or 72 h using one way-ANOVA with post hoc Dunnett multiple comparison test. Data are mean ± SEM. ns not significant, * p≤0.05, ** p≤0.01, *** p≤0.001 (n=4 biological replicates). Data information: Scale bars, , 50 µm",
    "ncbi_link": "CCL5: 6352
Tert: 7015"
  },
  {
    "caption": "(c) Representative images of CD45 immunofluorescence  labeling of P7 dorsal skin  sections from Dnmt1f/f, Dnmt1Δ/Δep, and Dnmt1Δ/Δep Cgas-/- mice. Dashed lines indicate the  dermal-epidermal border. (d) Quantification of CD45-positve cells. Tissue sections approximately 1 cm in length were scanned and the area of CD45 positive cells per area of nuclei was quantified using ImageJ. Sections obtained from five mice per genotype were analyzed and calculated values were compared using one way-ANOVA with post hoc Holm-Sidak multiple comparison test. Data are mean ± SEM. ** p≤0.01, *** p≤0.001. Data information: Scale bars, 100 µm",
    "ncbi_link": "Cgas: 214763
Dnmt1: 13433"
  },
  {
    "caption": "(e) Epidermis obtained from P7 control, Dnmt1Δ/Δep, Cgas-/- and Dnmt1Δ/Δep Cgas-/- mice  was analyzed for relative mRNA expression  levels of immune related genes using one way-ANOVA with post hoc Holm-Sidak multiple comparison test. Data are mean ± SEM. ns not significant, * p≤0.05, **** p≤0.0001. At least 7  mice per genotype were used.",
    "ncbi_link": "Cgas: 214763
Dnmt1: 13433"
  },
  {
    "caption": "(A) FAK immunoblotting was performed on macrophages isolated from the peritoneum of WT and FAKΔmyeloid mice.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(B) WT and FAK−/− PEMs were incubated with S. typhimurium strain ΔinvG for 0-5 hours before immunoblotting with the indicated antibodies.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(C, E and G) WT PEMs expressing GFP-FAK were incubated with either ΔinvG Salmonella (C), LPS-coated beads (E) or E. coli (G) for a total of 5 hours before analysis by immunofluorescence. Cells were co-stained with antibodies recognizing LAMP1 (red). Dapi was used to visualize nuclei and bacteria (blue). Bars represent 10 µm. Arrowheads indicate bacteria or beads in enlarged panel where bars represent 2 µm. (D, F and H) The percent of LAMP1-positive (gray bars) and LAMP1+GFP+ (black bars) ΔinvG Salmonella (D), LPS-coated beads (F) and E. coli (H) was quantified. At least 100 bacteria were counted per condition; N = 3.",
    "ncbi_link": "invG: 1254421"
  },
  {
    "caption": "A) TLR4−/− PEMs were incubated with ΔinvG Salmonella for 0-5 hours before immunoblotting with the indicated antibodies.",
    "ncbi_link": "invG: 1254421
TLR4: 21898"
  },
  {
    "caption": "(D) WT PEMs were incubated with the orgA::tet; spiA::kan Salmonella strain deficient in both the SPI1 and SPI2 T3SSs (ΔSPI1ΔSPI2) for 0-5 hours before immunoblotting with the indicated antibodies.",
    "ncbi_link": "orgA: 1254393
SPI1: 1249311
SPI2: 1249313
spiA: 1248100"
  },
  {
    "caption": "(E) WT PEMs expressing GFP-FAK were incubated with ΔSPI1ΔSPI2 Salmonella for a total of 5 hours before analysis by immunofluorescence. Cells were co-stained with antibodies recognizing LAMP1 (red). DAPI was used to visualize nuclei and bacteria (blue). Bars represent 10 µm or 2 µm in enlarged inset.",
    "ncbi_link": "SPI1: 1249311
SPI2: 1249313"
  },
  {
    "caption": "(A) WT and FAK−/− PEMs were incubated for 0-5 hours with ΔinvG Salmonella before immunoblotting with the indicated antibodies.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(B) WT PEMs were pretreated for 1 hour with the FAK-kinase inhibitor PF-228 (0.5 µm) before incubation with ΔinvG Salmonella for 5 hours. Lysates were immunoblotted with the indicated antibodies.",
    "ncbi_link": "invG: 1254421"
  },
  {
    "caption": "(C-D) WT or FAK−/− macrophages were incubated with either the ΔΣΠΙ1ΔΣΠΙ2 strain (C) or LPS-coated beads (D) for 0-5 hours before immunoblotting with the indicated antibodies. In panels C and D, WT PEMs were also incubated with ΔinvG (5 h) for comparison of Akt activation. Vertical white lines in panel D indicate non-contiguous lanes generated from a single exposure.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(F) WT PEMs expressing HA-Akt were either left untreated or incubated with ΔinvG Salmonella for 5 hours. Lysates were subjected to immunoprecipitation (IP) with anti-HA antibodies before immunoblotting for FAK and HA. In parallel, lysates were immunoblotted for FAK, HA and ERK1/2 to control for the level of expression.",
    "ncbi_link": "invG: 1254421"
  },
  {
    "caption": "G) WT and FAK−/− macrophages expressing HA-Akt were stained with anti-HA and anti-LAMP1 before analysis by confocal microscopy. White boxes show enlarged regions in lower panel. Arrows indicate HA+LAMP+ Salmonella evident in WT PEMs. (H) The percentage of ΔΣΠΙ1ΔΣΠΙ2 (first grouping) or ΔinvG (second grouping) Salmonella co-localizing with HA and LAMP-1 5 h post-infection. At least 100 bacteria were counted per condition. Values are means ± SEM, N = 3, *p<0.05.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(A) WT and FAK−/− PEMs were incubated with S. typhimurium strain ΔinvG for 0-24 hours before immunoblotting with the indicated antibodies.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(B) WT PEMs were incubated with Akt inhibitor AKTV/triciribine (10 µm) for 30 minutes before infection with S. typhimurium strain ΔinvG for 5 hours. Lysates were immunoblotted with the indicated antibodies. (",
    "ncbi_link": "invG: 1254421"
  },
  {
    "caption": ". (C) WT and FAK−/− PEMs were incubated with S. typhimurium strain ΔinvG for a total of 5 hours before analysis with antibodies recognizing LC3. DAPI was used to visualize nuclei and bacteria. Bars represent 10 µm. White boxes show enlarged regions in inset panels, bars represent 2 µm. White arrowheads indicate LC3-negative bacteria, yellow arrow heads indicate LC3-positive bacteria (panels c, f). Yellow arrowhead in panel f denotes an LC3+ cluster of bacteria. (D) The percentage of ΔinvG (first grouping) or ΔΣΠΙ1ΔΣΠΙ2 (second grouping) Salmonella co-localizing with LC3 at the indicated time points is displayed. At least 100 bacteria were counted per condition per time point. Values are means ± SEM, N = 3, *p<0.05.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(E) WT and FAK−/− PEMs were incubated with S. typhimurium strain ΔinvG for 5 h with or without Bafilomycin A1 (300 ng) before immunoblotting with the indicated antibodies. Vertical white line indicate non-contiguous lanes generated from a single exposure.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(F) FAK−/− PEMs were incubated with DQ-BSA-red for 1 hour before infection with S. typhimurium strain ΔinvG for 5 h. Cells were co-stained for LC3 and DAPI was used to visualize nuclei and bacteria. White boxes show enlarged regions in inset panel.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "G) WT PEMs were pretreated with the mTORC1 inhibitor rapamycin (4 µm) for 1 hour before incubation with ΔinvG Salmonella for a further 5 hours. Cells were lysed before immunoblotting with the indicated antibodies.",
    "ncbi_link": "invG: 1254421"
  },
  {
    "caption": "(H) WT and FAK−/− PEMs were pretreated with rapamycin (4 µm), Akt inhibitor AKTV/triciribine (10 µm) or left untreated (-Tx) or before infection with S. typhimurium strain ΔinvG for a further 5 hours. WT macrophages were also pretreated with the FAK inhibitor PF228 (0.5 µm) for 1 hour prior to incubation with ΔinvG Salmonella for 5 hours. Cells were then assessed for the percentage of ΔinvG Salmonella co-localizing with LC3. At least 100 bacteria were counted per condition. Values are means ± SEM, N = 3, *p<0.05. N.s. not significant.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "A) WT and FAK−/− PEMs were incubated with LPS-coated beads (50∶1; beads∶cell) for 1 hour before analysis with antibodies recognizing LC3. DAPI was used to visualize nuclei. Bars represent 10 µm. The percentage of LPS-beads co-localizing with LC3 is displayed to the right. At least 100 beads were counted per condition. Values are means ± SEM, N = 3.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(B) PEMs were treated with Atg5, ULK1 or control siRNAs for 48 hours before immunoblotting with the indicated antibodies.",
    "ncbi_link": "Atg5: 11793
ULK1: 22241"
  },
  {
    "caption": ". (C-D) FAK−/− PEMs treated with Atg5, ULK1 or control siRNA for 48 hours were incubated with LPS-coated beads or ΔinvG Salmonella for 1 or 5 hours before analysis with antibodies recognizing LC3. The percentage of LPS-beads or Salmonella co-localizing with LC3 is displayed to the right. At least 100 beads or bacteria were counted per condition. Values are means ± SEM, N = 3.",
    "ncbi_link": "Atg5: 11793
invG: 1254421
FAK: 14083
ULK1: 22241"
  },
  {
    "caption": "E) WT and FAK−/− PEMs were infected with ΔinvG for 5 hours before preparation and examination by transmission electron microscopy (TEM). Arrowheads indicate double membrane.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(A) WT and FAK−/− PEMs were incubated with S. typhimurium strain ΔinvG for 1.5, 3 and 5 hours. Bacterial survival was then assayed using a standard gentamycin resistance assay described in the Materials and Methods. Values are means ± SEM, N = 6, *p<0.05.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(B) WT and FAK−/− PEMs were pretreated with IFN-γ (50 ng/ml), rapamycin (4 µm), or left untreated before incubation with ΔinvG Salmonella for 3 hours. Bacterial survival was then assayed as described in (A). Values are means ± SEM, N = 6, *p<0.05.",
    "ncbi_link": "invG: 1254421
FAK: 14083"
  },
  {
    "caption": "(C) PEMs were treated with control siRNA or depleted of Atg5 before incubation with ΔinvG Salmonella for 3 hours. Bacterial survival was then assayed as described in (A). Values are means ± SEM, N = 3, *p<0.05 vs WT siControl.",
    "ncbi_link": "Atg5: 11793
invG: 1254421"
  },
  {
    "caption": ". (D) Bacterial loads in WT (black circles) and FAKΔmyeloid mice (white circles) in the indicated tissues 5 days after oral infection with S. typhimurium strain SL1344. Each point indicates data from an individual mouse. *p<0.05.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(E) Hematoxylin and eosin (H&E) staining of spleen isolated from WT and FAKΔmyeloid mice 5 days post-infection with S. typhimurium strain SL1344. Arrows indicate areas of leukocyte infiltration. Lesion indicated by yellow arrow is outlined in the higher magnification panel to the right. Bars represent 200 µm and 50 µm.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": ". (F) Gr-1 immunostaining of spleens isolated from WT and FAKΔmyeloid mice 5 days post-infection with S. typhimurium strain SL1344. Panels b and d are enlarged sections indicated by black boxes in panels a and c. Gr-1-positive cells appear red-brown.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "A, Misreading (A) were measured by dual luciferase gain-of-function assays using wild-type mitohybrid ribosomes (n=8 misreading, mutant A1555G mitohybrid ribosomes (n=8 misreading, E. coli wild-type ribosomes (n=9), E.coli mutant A127Y ribosomes (n=9), M. smegmatis merodiploid wild-type ribosomes (n=9), and M. smegmatis merodiploid mutant S152Y ribosomes (n=9). Mistranslation was determined by assessing the misreading at His245 (CAC codon) of the F-luc gene that was replaced by the near-cognate codon CGC or the non-cognate codon AGA, both encoding for Arg. Results are derived by calculating mutant hFluc/hRluc activity related to wild-type hFluc/hRluc activity.",
    "ncbi_link": "F-luc: 
Fluc: 
Rluc: "
  },
  {
    "caption": "read-through (B) were measured by dual luciferase gain-of-function assays using wild-type mitohybrid ribosomes n=4 read-through), mutant A1555G mitohybrid ribosomes n=4 read-through), E. coli wild-type ribosomes (n=9), E.coli mutant A127Y ribosomes (n=9), M. smegmatis merodiploid wild-type ribosomes (n=9), and M. smegmatis merodiploid mutant S152Y ribosomes (n=9). To determine read-through the Asp357 (GAC codon) of the F-luc gene was replaced by the nonsense TGA stop codon. Results are derived by calculating mutant hFluc/hRluc activity related to wild-type hFluc/hRluc activity.",
    "ncbi_link": "F-luc: 
Fluc: 
Rluc: "
  },
  {
    "caption": "C Ratio of 35S-Cysteine and 35S-Methionine incorporation by in-vitro translation using wild-type mitohybrid ribosomes, mutant A1555G mitohybrid ribosomes, and MT-CO1 mRNA. Following immunoprecipitation, the MT-CO1 band was quantified by autoradiography, wild-type mitohybrid ribosomes were set as 1 (n=3), error bars indicate SEM; ****p<0.001 (Student's t-test).",
    "ncbi_link": "MT-CO1: 4512"
  },
  {
    "caption": "D Ratio of 35S-Cysteine and 35S-Methionine incorporation by in-vitro translation in the presence of tobramycin using wild-type mitohybrid ribosomes, mutant A1555G mitohybrid ribosomes, and MT-CO1 mRNA; the MT-CO1 band was quantified by autoradiography.",
    "ncbi_link": "MT-CO1: 4512"
  },
  {
    "caption": "E Misreading of wild-type mitohybrid ribosomes and mutant A1555G mitohybrid ribosomes in the presence of tobramycin. Misreading was assessed by dual luciferase assay, and results derived by calculating mutant hFluc/hRluc activity related to wild-type hFluc/hRluc activity.",
    "ncbi_link": "Fluc: 
Rluc: "
  },
  {
    "caption": "F In-vitro translation of MT-CO1-TGA mRNA and MT-CO1-AGA mRNA using mutant A1555G mitohybrid ribosomes in the presence of tobramycin (0 - 20 µM). Autoradiography of immunoprecipitated MT-CO1 proteins; top: 35S-Met labelling, bottom: 14C-Lys labelling. In-organello translated 35S-Met labelled MT-CO1 was used as a marker. * MT-CO1, ** MT-CO1 extended by read-through, MT-CO1 AGA-polyA and MT-CO1 TGA-polyA constructs used for in-vitro translation are schematized.",
    "ncbi_link": "MT-CO1: 4512"
  },
  {
    "caption": "G Ratio of 14C-Lys and 35S-Met labelled immunoprecipitated MT-CO1 proteins. In-vitro translation using MT-CO1-TGA mRNA, MT-CO1-AGA mRNA, and mutant A1555G mitohybrid ribosomes in the presence of tobramycin (0 - 20 µM). The corresponding MT-CO1 band was quantified by autoradiography.",
    "ncbi_link": "MT-CO1: 4512"
  },
  {
    "caption": "Ratio of 35S-Cys and 35S-Met labelled MT-CO1 protein synthesized in in-organello translation using mitochondria from HEK293 MRPS5 wild-type cells and HEK MRPS5 mutant V336Y cells. Following in-organello translation, proteins were immunoprecipitated and analyzed by autoradiography. MT-CO1 bands quantified and ratios calculated. The ratio of the MRPS5 wild-type was set as 1 (n=8 clones), error bars indicate SD; ***p<0.0001 (Student's t-test).",
    "ncbi_link": "MRPS5: 64969"
  },
  {
    "caption": "D Autoradiography of in-organello mitochondrial translation products derived from HEK293 MRPS5 wild-type cells in the presence of tobramycin (0-750 µM). Proteins were 35S-Met labeled and loaded either directly on SDS-PAGE (total, top) or following poly-lysine immunoprecipitation (bottom). * MT-CO1 and ** MT-CO1 with poly-lysine extension.",
    "ncbi_link": "MRPS5: 64969"
  },
  {
    "caption": "E Quantification of MT-CO1 proteins in HEK293 MRPS5 wild-type cells and HEK293 MRPS5 mutant V336Y cells. In-organello mitochondrial translation in the presence of 35S-Met and 750 µM tobramycin. Proteins were loaded either directly on SDS-PAGE (total) or following poly-lysine immunoprecipitation and analyzed by autoradiography. For total protein samples the MT-CO1 band was quantified, for poly-lysine immunoprecipitated samples the extended MT-CO1 band was quantified and the ratio of extended MT-CO1/total MT-CO1 calculated. The ratio of MRPS5 wild-type was set as 1 (MRPS5 wild-type, n=5 clones, MRPS5 V336Y, n=7 clones), error bars indicate SD; ***p<0.0001 (Student's t-test).",
    "ncbi_link": "MRPS5: 64969"
  },
  {
    "caption": "Noise exposure and ABR measurements. Exposure of mice to broadband noise (2-10 kHz) of either 108 or 110 dB SPL resulted in elevations of auditory thresholds. Thresholds in Mrps5V338Y/V338Y mutant mice (black bars) were significantly higher after exposure than thresholds in littermates (open bars), (p<0.0001, two-way ANOVA for combined 108 and 110 dB data). Frequencies of 12, 24 and 32 kHz were selected for measurement to cover the mid-frequency to high-frequency regions of the cochlea. n=6 for baseline littermates; n=6 for baseline mutants; n=3 for all noise exposures.",
    "ncbi_link": "Mrps5: 77721"
  },
  {
    "caption": "F Subcellular localization of PHGDH was determined by western blot in PLC cells overexpressing of Flag-tagged wild-type PHGDH, PHGDH∆SBD1, or PHGDH∆RD mutants. WCL: whole-cell lysates, Mito: mitochondria. Tom20 was used as loading control.",
    "ncbi_link": "Flag: 
PHGDH: "
  },
  {
    "caption": "A The oxygen consumption rate (OCR) was measured by successive injections of oligomycin (oligo), FCCP, and antimycin A/rotenone (AA/Rot) in PLC cells infected with viruses expressing nontargeting control (NTC) shRNA or shPHGDH. Basal respiration, ATP-linked respiration, and maximal respiration were analysed with the OCR curve.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "B Western blot analysis of mtDNA-encoded proteins in PLC cells stably expressing NTC or shPHGDH and empty vector (EV) or PLVX-PHGDH. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: 
PHGDH: 26227"
  },
  {
    "caption": "C PLC cells with endogenous PHGDH knockdown were further infected with viruses expressing EV or PLVX-PHGDH prior to western blot analysis of mtDNA-encoded proteins. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: 
PHGDH: 26227"
  },
  {
    "caption": "D PLC cells expressing NTC or shPHGDH were treated with 100 μg/ml cycloheximide (CHX) for 20 min prior to puromycin treatment for 15 min. Purified mitochondrial lysates were subjected to a SUnSET assay with an anti-puromycin antibody to measure the actively translated polypeptide chains. Western blot analysis of PHGDH confirmed the knockdown efficiency of the PHGDH shRNAs. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "F PLC cells with or without PLVX-Flag-PHGDH overexpression were treated with DMSO or 50 μM chloramphenicol (CAP) in combination with 50 μM thiamphenicol (TAP) for 24 h prior to SUnSET assays. The assays were performed using whole-cell lysate.",
    "ncbi_link": "Flag: 
PHGDH: "
  },
  {
    "caption": "G PLC cells with or without PLVX-PHGDH overexpression were treated with DMSO or 50 μM CAP in combination with 50 μM TAP for 24 h prior to western blot analysis of mtDNA-encoded proteins. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: "
  },
  {
    "caption": "H The translation efficiency of mtDNA-encoded proteins was determined by a SUnSET assay in PLC cells with endogenous PHGDH knockdown that were further infected with viruses expressing EV, wild-type PHGDH, or the catalytically inactive PHGDH mutant PHGDHR236E as indicated. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: 
PHGDH: 26227"
  },
  {
    "caption": "I mtDNA-encoded proteins were analysed by western blotting in PLC cells overexpressing EV, wild-type PHGDH, or PHGDHR236E. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: "
  },
  {
    "caption": "A HEK293T cells were transfected with Flag-tagged PHGDH in combination with HA-tagged EV, mtIF2, mtIF3, mtEFTu, mtEFG1, mtEFG2, or mtRRF. Co-immunoprecipitation (Co-IP) was performed with an anti-Flag antibody prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
mtEFG1: 
mtEFG2: 
mtEFTu: 
mtRRF: 
PHGDH: 
mtIF2: 4528
mtIF3: 219402"
  },
  {
    "caption": "B HEK293T cells were transfected with HA-tagged PHGDHWT or PHGDHR236E in combination with Flag-EV or Flag-mtEFG2, and Co-IP was performed with an anti-Flag antibody prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
mtEFG2: 
PHGDH: "
  },
  {
    "caption": "C HEK293T cells were transfected with HA-tagged PHGDHWT or PHGDHR236E in combination with Flag-EV or Flag-ANT2, and Co-IP was performed with an anti-Flag antibody prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
PHGDH: 
ANT2: 54978"
  },
  {
    "caption": "D HEK293T cells were transfected with HA-mtEFG2 in combination with Flag-EV or Flag-ANT2, and Co-IP was performed with an anti-Flag antibody prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
mtEFG2: 
ANT2: 54978"
  },
  {
    "caption": "E GST pull-down of His-PHGDHWT and His-PHGDHR236E by GST-ANT2 using proteins purified in E. coli, followed by western blot analysis with anti-His and anti-GST antibodies.",
    "ncbi_link": "GST: 
His: 
PHGDH: 
ANT2: 54978"
  },
  {
    "caption": "F GST pull-down of His-mtEFG2 by GST-ANT2 using proteins purified in E. coli, followed by western blot analysis with anti-His and anti-GST antibodies.",
    "ncbi_link": "GST: 
His: 
mtEFG2: 
ANT2: 54978"
  },
  {
    "caption": "G PLC cells stably expressing Flag-mtEFG2 and HA-PHGDH were further infected with viruses expressing NTC or shANT2, and then cell lysates were immunoprecipitated with an anti-Flag antibody or IgG prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
mtEFG2: 
PHGDH: 
ANT2: 54978"
  },
  {
    "caption": "H PLC cells overexpressing PHGDH were further infected with viruses expressing NTC or shANT2. The translation efficiency was measured by a SUnSET assay.",
    "ncbi_link": "PHGDH: 
ANT2: 54978"
  },
  {
    "caption": "I PLC cells overexpressing PLVX-PHGDH were further infected with viruses expressing NTC or shANT2. The expression of mtDNA-encoded proteins was determined by western blotting. β-Actin was used as the loading control.",
    "ncbi_link": "PHGDH: 
ANT2: 54978"
  },
  {
    "caption": "PLC cells overexpressing PHGDH were further infected with viruses expressing NTC or shmtEFG2. The translation efficiency was measured by a SUnSET assay.",
    "ncbi_link": "mtEFG2: 
PHGDH: "
  },
  {
    "caption": "K PLC cells overexpressing pSin-3xFlag-PHGDH were further infected with viruses expressing NTC or shmtEFG2. The expression of mtDNA-encoded proteins was determined by western blotting. β-Actin was used as the loading control.",
    "ncbi_link": "Flag: 
mtEFG2: 
PHGDH: "
  },
  {
    "caption": "A HEK293T cells were transfected with HA-mtEFG2 in combination with Flag-EV or Flag-mtRRF, and Co-IP was performed with an anti-Flag antibody prior to western blot analysis.",
    "ncbi_link": "Flag: 
HA: 
mtEFG2: 
mtRRF: "
  },
  {
    "caption": "B PLC cells stably expressing Flag-mtEFG2 and HA-mtRRF were further infected with viruses expressing NTC or shPHGDH, and then cell lysates were immunoprecipitated with anti-Flag antibody or IgG prior to western blot analysis.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "C PLC cells stably overexpressing mtEFG2 were further infected with viruses expressing NTC or shPHGDH. The translation efficiency was measured by a SUnSET assay.",
    "ncbi_link": "mtEFG2: 
PHGDH: 26227"
  },
  {
    "caption": "D PLC cells stably overexpressing mtEFG2 were further infected with viruses expressing NTC or shPHGDH. mtDNA-encoded proteins were analysed by western blot. β-Actin was used as the loading control.",
    "ncbi_link": "mtEFG2: 
PHGDH: 26227"
  },
  {
    "caption": "F Binding of mtDNA-encoded mRNA by endogenous MRPL44 (representing mitochondrial ribosomes) was evaluated by RNA immunoprecipitation (RIP) in PLC cells with PHGDH knockdown.",
    "ncbi_link": "PHGDH: 26227"
  },
  {
    "caption": "G The same amount of mitochondria from PLC cells expressing NTC or shPHGDH treated with CAP and TAP were loaded onto the sucrose density gradient. After centrifugation, all fractions were subjected to western blot analysis of MRPS35, MRPL44, and MRPL48 proteins. RNA concentrations of ND6 were measured.",
    "ncbi_link": "ND6: 4541
PHGDH: 26227"
  },
  {
    "caption": "A PLC cells overexpressing EV, PHGDHWT, or PHGDHR236E were further infected with viruses expressing NTC or shmtEFG2. The OCR was measured after successive injections of oligomycin (oligo), FCCP, and antimycin A/rotenone (AA/Rot). Basal respiration, ATP-linked respiration, and maximal respiration were analysed with the OCR curve.",
    "ncbi_link": "mtEFG2: 
PHGDH: "
  },
  {
    "caption": "B PLC cells overexpressing EV, PHGDHWT, or PHGDHR236E were further infected with viruses expressing NTC or shmtEFG2 prior to western blot analysis. β-Actin was used as the loading control (left). Cell growth curves were constructed by cell counting with trypan blue exclusion (right).",
    "ncbi_link": "mtEFG2: 
PHGDH: "
  },
  {
    "caption": "C PLC cells overexpressing EV, PHGDHWT, or PHGDHR236E were further treated with H2O or tigecycline prior to western blot analysis. β-Actin was used as the loading control (left). Cell growth curves were determined by cell counting with trypan blue exclusion (right).",
    "ncbi_link": "PHGDH: "
  },
  {
    "caption": "D-F PLC cells overexpressing EV or PHGDH were further infected with viruses expressing NTC or shmtEFG2. Then, these cells were subcutaneously injected into male nude mice (n = 5 in each group). Tumour sizes were measured beginning 14 days after inoculation (D). At the end of the experiment, the tumours were excised (E), and PHGDH and mtEFG2 expression in tumour lysates was analysed by western blotting (F).",
    "ncbi_link": "mtEFG2: 
PHGDH: "
  },
  {
    "caption": "G-I PLC cells overexpressing EV or PHGDH were subcutaneously injected into male nude mice (n = 5 in each group). Mice were intraperitoneally injected with 100 mg/kg tigecycline daily beginning 14 days after inoculation. Tumour sizes were measured beginning 14 days after inoculation (G). At the end of the experiment, the tumours were excised (H), and PHGDH expression in tumour lysates was analysed by western blotting (I).",
    "ncbi_link": "PHGDH: "
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs unstimulated or infected with flagellin-expressing STm  Cell pellets collected at the indicated time points after STm  infection were lysed, fractionated by SDS-PAGE and immunoblotted  for caspase-1 (E, F) (E Representative immunoblots  showing pro-caspase-1  (pro-casp.-1) and cleaved p20 (casp.-1 p20) bands (E) (F, Quantification of band intensities for caspase-1 p20 normalized to pro-caspase-1 and actin  (E) from three independent experiments are shown as fold change (F Data information: Data represent mean ± SD. * p<0.05; **p<0.01; ***p<0.001. Two-tailed Student's t-test.",
    "ncbi_link": "SLC15A4: 100561"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs  unstimulated or infected with flagellin-expressing STm  Cell pellets collected at the indicated time points  after STm  infection were lysed, fractionated by SDS-PAGE and immunoblotted  for GSDMD  or LC-3 G). Representative immunoblots  showing GSDMD  full length (GSDMD  FL), cleaved GSDMD  N-terminal fragment (GSDMD  N-ter), LC3-II and LC3-I  bands in cell lysates (G). H, Quantification of band intensities for GSDMD  N-ter normalized to actin  (G) and LC3-II  normalized to LC3-I and actin  (H) from three independent experiments are shown as fold change , H) Data information: Data represent mean ± SD. * p<0.05; **p<0.01; ***p<0.001. Two-tailed Student's t-test.",
    "ncbi_link": "SLC15A4: 100561"
  },
  {
    "caption": "Intestinal CD11c+ DCs  were isolated from colons of WT and SLC15A4feeble mice on day 16 and cultured overnight. B. Cell pellets from three independent experiments were immunoblotted for LC3 and actin. Upper panel. Representative immunoblot. Lower panel. Quantification of band intensities for LC3-II normalized to LC3-I  and actin  are shown as fold induction relative to samples from untreated mice. Note that LC3-I  signal from ex vivo samples is almost undetectable. Data information: Mean is indicated. **p<0.01. Mann-Whitney non-parametric statistical test.",
    "ncbi_link": "SLC15A4: 100561"
  },
  {
    "caption": "WT or  SLC15A4feeble BMDCs expressing ASC-GFP  and mCherry-LC3  (A, B were infected with flagellin-expressing STm and fixed A. Cells were analyzed by  fluorescence microscopy. Representative images showing ASC  speck (green) relative to mCherry-LC3  (red) in two infected WT and SLC15A4feeble DCs  each. B. Quantification of LC3  fluorescence per unit area in a radius of 1 μm surrounding the ASC  speck in 20 cells per cell type in each of 3 independent experiments. N, nucleus. Corresponding DIC images show nuclear  position. Scale bar, 8 μm. Data information: Data represent mean ± SD. **p<0.01. Two-tailed Student's t-test.",
    "ncbi_link": "GFP: 
mCherry: 
LC3: 440738///84557///81631
ASC: 29108
SLC15A4: 100561"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs non-transduced (C) were infected with flagellin-expressing STm  and fixed C. Cells were stained  for endogenous ASC  and p62, labeled with DAPI  and analyzed by fluorescence microscopy. Representative images showing ASC  speck (red) relative to p62  (green) in two infected WT and SLC15A4feeble DCs  each. Note p62 staining  surrounding ASC  specks in SLC15A4feeble DCs. D. Quantification of perinuclear  (within a radius of 3 μm from the nucleus) ASC  specks in at least 30 cells per cell type in each of 3 independent experiments. N, nucleus. Corresponding DIC  images show nuclear  position. Scale bar, 8 μm. Data information: Data represent mean ± SD. **p<0.01. Two-tailed Student's t-test.",
    "ncbi_link": "SLC15A4: 100561"
  },
  {
    "caption": "SLC15A4feeble BMDCs  transduced with SLC15A4-GFP  (E were infected with flagellin-expressing STm  and fixed (E, Cells were stained  for endogenous ASC, labeled with DAPI  and analyzed by fluorescence microscopy. Representative images showing ASC  speck (red) and SLC15A4-GFP  (green) in SLC15A4feeble DCs  together with non-transduced SLC15A4feeble DCs. Note the perinuclear  positioning of ASC  specks in the transduced cells (E). N, nucleus. Dotted white lines, cell outlines. Corresponding DIC  images show nuclear  position. Scale bar, 8 μm.",
    "ncbi_link": "GFP: 
SLC15A4: 100561
SLC15A4: 121260"
  },
  {
    "caption": "SLC15A4feeble BMDCs   transduced with SLC15A4-GFP   F, were infected with flagellin-expressing STm   and fixed Quantification of perinuclear   (within a radius of 3 μm from the nucleus) and non-perinuclear ASC   specks in at least 30 cells per cell type in each of three independent experiments (F). Data information: Data represent mean ± SD. **p<0.01. Two-tailed Student's t-test.",
    "ncbi_link": "GFP: 
SLC15A4: 100561
SLC15A4: 121260"
  },
  {
    "caption": "SLC15A4feeble BMDCs  transduced with SLC15A4-GFP  G) were infected with flagellin-expressing STm  and lysed (G) 1 h after infection. G. Representative immunoblots  showing pro-caspase-1 (pro-casp.-1) and cleaved p20 (casp.-1 p20), LC3-II and LC3-I, and actin  bands.",
    "ncbi_link": "GFP: 
SLC15A4: 100561
SLC15A4: 121260"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs transduced with constitutively active RagB  (RagBQ99L) or metap2  (control) were infected with flagellin-expressing STm. (A, B). Cell pellets collected 1 h after STm  infection were lysed, fractionated by SDS-PAGE and immunoblotted  for phospho  (P) and total mTOR, ULK1  kinase, p70  kinase and S6, FLAG  and actin. Representative immunoblots. Non-specific band right above FLAG-RagBQ99L is indicated with an asterisk (A). Quantification of band intensities for P-mTOR  normalized to total mTOR, P-ULK1  normalized to total ULK1, P-p70  normalized to total p70  and P-S6  normalized to S6, in transduced cells from 3 independent experiments are shown as fold change relative to WT control (B). Data information: Data represent mean ± SD. **p<0.01; ***p<0.001. Two-tailed Student's t-test.",
    "ncbi_link": "metap2: 10988
RagB: 10325
SLC15A4: 100561"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs  transduced with constitutively active RagB  (RagBQ99L) or metap2  (control) (E, Cell pellets were probed for caspase-1, GSDMD, actin  (E, Representative immunoblots  showing pro-caspase-1  (pro-casp.-1) and cleaved p20 (casp.-1  p20), GSDMD  full length (GSDMD  FL) and cleaved GSDMD  N-terminal fragment (GSDMD  N-ter) bands.",
    "ncbi_link": "metap2: 10988
RagB: 10325
SLC15A4: 100561"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs  transduced with non-target control, ATG5  or ATG7  shRNAs G) G). Cell pellets were probed for caspase-1, GSDMD, actin  , ATG5  and ATG 7 (G). Representative immunoblots  showing pro-caspase-1 (pro-casp.-1) and cleaved p20 (casp.-1 p20), GSDMD  full length (GSDMD  FL) and cleaved GSDMD  N-terminal fragment (GSDMD  N-ter) bands.",
    "ncbi_link": "ATG5: 11793
ATG7: 74244
SLC15A4: 100561"
  },
  {
    "caption": "WT or SLC15A4feeble BMDCs  transduced with constitutively active RagB  (RagBQ99L) or metap2  (control) H, I) and mcherry-LC3  (H, I), (H, I). Cells were stained  for endogenous ASC, labeled with DAPI  and analyzed by fluorescence microscopy. Representative images showing ASC  speck (green) and LC3  (red) in SLC15A4feeble DCs  (H). Quantification of perinuclear  (within a radius of 3 μm from the nucleus) in at least 30 cells per cell type in each of three independent experiments (I). N, nucleus. Corresponding DIC  images show nuclear  position. Scale bar, 8 μ Data information: Data represent mean ± SD. **p<0.01; ***p<0.001. Two-tailed Student's t-test.",
    "ncbi_link": "mcherry: 
LC3: 440738///84557///81631
metap2: 10988
RagB: 10325
SLC15A4: 100561"
  },
  {
    "caption": "B Western blot analysis (probing with an anti-FLAG mAb) to detect cleavage of the artificial substrate by wild-type (WT)/inactive (S201A) GlpG encoded on pBAD33 with/without arabinose (Ara.). rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red, arrows, respectively. Controls, empty pBAD33 (empty)",
    "ncbi_link": "GlpG: "
  },
  {
    "caption": "C Western blot analysis to detect cleavage of the artificial substrate by wild-type (WT)/modified (S133A or H187A) Rhom7 encoded on pBAD33 with/without arabinose (Ara.). , rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, and blue arrows, respectively. Controls, empty pBAD33 (empty) and wild-type S. sonnei (Ss).",
    "ncbi_link": "Rhom7: "
  },
  {
    "caption": "D Activity of Rhom7 with/without its 7th TMD and/or C-terminal domain. rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, , and blue arrows, respectively. Controls, empty pBAD33 (empty) and wild-type S. sonnei (Ss).",
    "ncbi_link": "Rhom7: "
  },
  {
    "caption": "C Western blot analysis of candidate substrates reproducibly cleaved by GlpG from the screen. Data information: In (C rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red, arrows, respectively. Controls, inactive enzymes and wild-type S. sonnei (Ss).",
    "ncbi_link": "GlpG: "
  },
  {
    "caption": "D Western blot analysis of candidate substrates reproducibly cleaved by Rhom7 from the screen. Data information: In D) rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, red, and blue arrows, respectively. Controls, inactive enzymes and wild-type S. sonnei (Ss).",
    "ncbi_link": "Rhom7: "
  },
  {
    "caption": "Western blot analysis (probing with an anti-FLAG mAb) to detect cleavage of HybO with (+)/without (-) chromosomal (native) or pBAD33-encoded rhomboids (plasmid). homboid substrates that are uncleaved, are marked by black, rrows, ild-type S. sonnei, Ss. Wild-type (WT)/inactive (SAHA: alanine substitution of the catalytic serine and histidine residues) enzymes were pBAD33-encoded (plasmid) in S. sonneiΔglpGΔrhom7.",
    "ncbi_link": "glpG: 
rhom7: "
  },
  {
    "caption": "Western blot analysis to detect cleavage of HybA with (+)/without (-) chromosomal (native) or pBAD33-encoded rhomboids (plasmid). rhomboid substrates that are uncleaved, cleaved by GlpG, or by Rhom7, are marked by black, red, and blue arrows, respectively. Wild-type S. sonnei, Ss. Wild-type (WT)/inactive (SAHA: alanine substitution of the catalytic serine and histidine residues) enzymes were pBAD33-encoded (plasmid) in S. sonneiΔglpGΔrhom7.",
    "ncbi_link": "glpG: 
rhom7: 
GlpG: 
Rhom7: "
  },
  {
    "caption": "Western blot analysis to detect cleavage of HybAG296F by endogenous or pBAD33-encoded rhomboid. Wild-type S. sonnei, Ss. rhomboid substrates that are uncleaved, cleaved by GlpG, or by Rhom7, re marked by black, red, and blue arrows, espectively. ild-type S. sonnei, Ss. Wild-type (WT)/inactive (SAHA: alanine substitution of the catalytic serine and histidine residues) enzymes were pBAD33-encoded (plasmid) in S. sonneiΔglpGΔrhom7.",
    "ncbi_link": "glpG: 
rhom7: 
GlpG: 
Rhom7: "
  },
  {
    "caption": "Western blot analysis to detect cleavage of HybAP300A by endogenous or pBAD33-encoded rhomboid. rhomboid substrates that are uncleaved, cleaved by GlpG, or by Rhom7, are marked by black, red, and blue arrows, respectively. Wild-type S. sonnei, Ss. Wild-type (WT)/inactive (SAHA: alanine substitution of the catalytic serine and histidine residues) enzymes were pBAD33-encoded (plasmid) in S. sonneiΔglpGΔrhom7.",
    "ncbi_link": "glpG: 
rhom7: 
GlpG: 
Rhom7: "
  },
  {
    "caption": "A Bacterial two-hybrid analysis with HybA and/or HybB fused chromosomally with the T25 and T18 domains of B. pertussis CyaA, respectively in the absence of endogenous CyaA. Bacteria were grown on LB agar containing 20 µg/ml X-gal at 37°C for 14 hours in the presence/absence of O2. Scale bar, 1 cm.",
    "ncbi_link": "CyaA: 
CyaA: 2664492"
  },
  {
    "caption": "B Western blot analysis to detect HybA cleavage in S. sonneiΔrhom7 by wild-type (+) or inactive (S201A) GlpG expressed chromosomally (native) or from pUC19 (plasmid) with (+)/without (-) HybB. HybA was expressed from its native locus or a plasmid (pHybA). HybA that is uncleaved or cleaved by GlpG is marked by black and red arrows, respectively.",
    "ncbi_link": "rhom7: 
GlpG: 
HybA: 
HybB: "
  },
  {
    "caption": "C Quantification of the ratio of cleaved/uncleaved HybA in strains with (+) or without (-) HybB. mean ± S.D. of three experiments. *, p<0.05; ****, p<0.0001 (One-way ANOVA).",
    "ncbi_link": "HybB: "
  },
  {
    "caption": "D Western blot analysis to detect GlpG-mediated cleavage of native tagged HybA at indicated times after blocking protein translation by the addition of chloramphenicol at T0 in the absence of HybB (-). , HybA that is uncleaved or cleaved by GlpG is marked by black and red arrows, respectively.",
    "ncbi_link": "GlpG: "
  },
  {
    "caption": "E Western blot analysis to detect GlpG-mediated cleavage of C-terminally sfCherry-3xFLAG tagged HybA at times after blocking protein translation by the addition of chloramphenicol at T0 in the presence of HybB (+). , HybA that is uncleaved or cleaved by GlpG is marked by black and red arrows, respectively.",
    "ncbi_link": "GlpG: 
HybB: "
  },
  {
    "caption": "F Growth of bacteria lacking hydrogenases (ΔhyaA-F ΔhycE +/- ΔhybO-G) or GlpG (ΔglpG), or expressing uncleavable HybB (hybAG296F) in 5% H2",
    "ncbi_link": "glpG: 
GlpG: 
hyaA-F: 
hybA: 
HybB: 
hybO: 
hycE: "
  },
  {
    "caption": "H S. sonnei growth in 10% H2 with plasmid expressed wild-type or non-functional (pglpGSAHA) GlpG.",
    "ncbi_link": "glpG: 
GlpG: "
  },
  {
    "caption": "B Western blot analysis (probing with an anti-FLAG mAb) to detect cleavage of FdoH cleavage in S. sonneiΔrhom7 with (+)/without (-) FdoI. rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red arrows, respectively.",
    "ncbi_link": "rhom7: 
FdoI: 
GlpG: "
  },
  {
    "caption": "C Western blot analysis to detect cleavage of FdnH in S. sonneiΔglpG with (+) or without (-) chromosomal Rhom7 (native), or wild-type (+)/inactive (SAHA) Rhom7 expressed from pBAD33 in S. sonneiΔglpGΔrhom7 with (+) or without (-) FdnI. rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, and blue arrows, respectively.",
    "ncbi_link": "glpG: 
rhom7: 
FdnI: 
Rhom7: "
  },
  {
    "caption": "E Western blot analysis to detect cleavage of wild-type (WT) or uncleavable (P300A) HybA by active (+) or inactive (S201A) chromosomal GlpG in the presence (+) or absence (-) of HybB. rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red arrows, respectively.",
    "ncbi_link": "GlpG: 
HybB: "
  },
  {
    "caption": "F Western blot analysis to detect cleavage of wild-type (WT) or modified (P259A) FdoH by active (+) or inactive (S201A) chromosomal GlpG in the presence (+) or absence (-) of FdoI. rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red arrows, respectively.",
    "ncbi_link": "FdoI: 
GlpG: "
  },
  {
    "caption": "G Western blot analysis to detect cleavage of wild-type (WT) or modified (P259A) FdnH with active (+) or inactive (SAHA) Rhom7 expressed from pBAD33 with (+) or without (-) FdnI. rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, blue arrows, respectively.",
    "ncbi_link": "FdnI: 
Rhom7: "
  },
  {
    "caption": "A Western blot analysis (probing with an anti-V5 mAb) to detect degradation of N-terminally V5-tagged wild-type (WT) or modified (P300A) HybA in S. sonneiΔrhom7 chromosomally expressing wild-type (+) or inactive (S201A) GlpG with (+) or without (-) HybB. Rhomboid substrates that are uncleaved, cleaved by GlpG, , are marked by black, red, arrows, respectively. Degradation products post rhomboid cleavage are marked by green arrows.",
    "ncbi_link": "rhom7: 
GlpG: 
HybB: "
  },
  {
    "caption": "B Degradation of V5-tagged HybA at times after blocking protein translation at T0 in the presence (+) or absence (-) of HybB. Rhomboid substrates that are uncleaved, cleaved by GlpG, black, red, arrows, respectively. Degradation products post rhomboid cleavage are marked by green arrows.",
    "ncbi_link": "GlpG: 
HybB: "
  },
  {
    "caption": "C Western blot analysis of N-terminally V5-tagged wild-type (WT) or modified (P259A) FdoH in S. sonneiΔrhom7 chromosomally expressing wild-type (+) or inactive (S201A) GlpG with (+)/without (-) FdoI. Rhomboid substrates that are uncleaved, cleaved by GlpG are marked by black, red, arrows, respectively.",
    "ncbi_link": "rhom7: 
FdoI: 
GlpG: "
  },
  {
    "caption": "D Western blot analysis of N-terminally V5-tagged wild-type (WT) or modified (P259A) FdnH in S. sonneiΔrhom7 with wild-type (+) or inactive (SAHA) Rhom7 expressed from pBAD33 with (+)/without (-) FdnI. Rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, blue arrows, respectively.",
    "ncbi_link": "rhom7: 
FdnI: 
Rhom7: "
  },
  {
    "caption": "Degradation of N-terminally V5-tagged wild-type (WT) or modified (P259A) FdoH in S. sonneiΔrhom7 with wild-type (+) or inactive (S201A, SAHA) GlpG expressed chromosomally (native) or from pUC19 (plasmid) without FdoI , +/- exposure to 400 µM CuCl2 for 30 min. : Rhomboid substrates that are uncleaved, cleaved by GlpG, are marked by black, red, arrows, respectively. Degradation products post rhomboid cleavage are marked by green arrows.",
    "ncbi_link": "rhom7: 
GlpG: "
  },
  {
    "caption": "F Degradation of N-terminally V5-tagged wild-type (WT) or modified (P259A) FdnH in S. sonneiΔrhom7 with wild-type (+) or inactive (S201A, SAHA) GlpG expressed from pUC19 (plasmid) without FdnI (-), , +/- exposure to 400 µM CuCl2 for 30 min. Rhomboid substrates that are uncleaved, cleaved by Rhom7, are marked by black, and blue arrows, respectively. Degradation products post rhomboid cleavage are marked by green arrows.",
    "ncbi_link": "rhom7: 
GlpG: 
Rhom7: "
  },
  {
    "caption": "A Western blot analysis probing the localisation and status of plasmid-encoded N-terminally V5-tagged wild-type (WT) or modified (P300A) HybA in S. sonneiΔrhom7ΔhybB with wild-type (+) or inactive (SAHA) GlpG expressed from pUC19. Whole cell lysate (Whole cell.), Sol (Sol.), Mem (detergent-solubilised, Mem.), and the Aggregate (Agg.) fractions are shown. HybA that is uncleaved, cleaved only by GlpG, and further degraded post GlpG cleavage is marked by black, red, and green arrows, respectively.",
    "ncbi_link": "hybB: 
rhom7: 
GlpG: 
HybA: "
  },
  {
    "caption": "Quantitative phosphoproteomics dataset showing that most phosphorylation events induced in rad9Δ cells are dependent on Mec1. These phosphoproteomic analyses were conducted in the presence of 0.02% MMS for 2 hours.",
    "ncbi_link": "Mec1: 852433
rad9: 851803"
  },
  {
    "caption": "Immunoblot analysis of Sgs1 N-terminus (amino acids 1-647) from cells treated with increasing doses of the DNA alkylating drug MMS in the absence of RAD9 and/or MEC1. This truncated Sgs1 protein was expressed from its native promoter in this and all subsequent experiments.",
    "ncbi_link": "MEC1: 852433
RAD9: 851803"
  },
  {
    "caption": "Rmi1, a component of the Sgs1-Top3-Rmi1 (STR) complex, is hyper-phosphorylated on S/T-Q motifs in rad9Δ cells.",
    "ncbi_link": "rad9: 851803
Rmi1: 856083
Sgs1: 855228
Top3: 850935"
  },
  {
    "caption": "Immunoblot showing co-immunoprecipitation of Dpb11 with Sgs1. Both DPB11-3xHA and SGS11-647-5xFLAG were expressed at their endogenous loci.",
    "ncbi_link": "HA: 
FLAG: 
DPB11: 853355
SGS1: 855228"
  },
  {
    "caption": "Immunoblots showing co-immunoprecipitation between Dpb11 and Sgs1 in the presence of 0.04% MMS in either wildtype, mec1Δ, tel1Δ or mec1Δ tel1Δ cell lines. DPB11-3HA was tagged at its endogenous locus and co-immunoprecipitated with SGS11-647-FLAG tagged and truncated at its endogenous locus.",
    "ncbi_link": "FLAG: 
HA: 
DPB11: 853355
mec1: 852433
SGS1: 855228
tel1: 852190"
  },
  {
    "caption": "Dilution assay of wild-type or rev3Δ cells expressing BRCT3/4-SGS1 in the presence of 0.0025% MMS.",
    "ncbi_link": "rev3: 855936
SGS1: 855228"
  },
  {
    "caption": "Measurement of BIR efficiency in cells carrying an empty vector or expressing DPB11BRCT3/4 fused to wild-type or mutant versions of SGS1. Mutants include a helicase deficient allele of SGS1 (SGS1hd) or an allele lacking the Top3 Interacting Motif (TIM; SGS1TIM). Error bars represent SEM of at least 3 replicate experiments. P value was calculated with a two-tailed, unpaired t-test. * = p≤0.05; ** = p≤0.01; *** = p ≤0.001. C. Measurement of BIR efficiency in cells carrying an empty vector or expressing DPB11BRCT3/4 fused to either SGS1, TOP3, or RMI1. Error bars represent SEM of at least 3 replicate experiments. P value was calculated with a two-tailed, unpaired t-test. * = p≤0.05; ** = p≤0.01; *** = p ≤0.001. D. Measurement of BIR efficiency in cells carrying an empty vector or DPB11BRCT3/4 fused to either SGS1, hBLM, PIF1, or RRM3. Error bars represent SEM of at least 3 replicate experiments. P value was calculated with a two-tailed, unpaired t-test. * = p≤0.05; ** = p≤0.01; *** = p ≤0.001.",
    "ncbi_link": "BLM: 641
DPB11: 853355
PIF1: 854941
RMI1: 856083
RRM3: 856426
SGS1: 855228
Top3: 850935
TOP3: 850935"
  },
  {
    "caption": "Serial dilution assay of sgs1Δ cell lines expressing either SGS1 or sgs1ΔACIDICPATCH.",
    "ncbi_link": "sgs1: 855228
SGS1: 855228"
  },
  {
    "caption": "BIR assay in rad9Δ sgs1Δ cell lines expressing either SGS1 or sgs1ΔACIDICPATCH. Error bars represent SEM of 3 independent experiments. Error bars represent SEM of at least 3 replicate experiments. P value was calculated with a two-tailed, unpaired t-test. * = p≤0.05; ** = p≤0.01; *** = p ≤0.001.",
    "ncbi_link": "rad9: 851803
sgs1: 855228
SGS1: 855228"
  },
  {
    "caption": "C-E. Full length GFP:Mud shows the wild type pattern of localization in mud3/mud4 mitotic follicle cells (C) and rescues spindle orientation (D E). GFP:Mud lacking the Pins binding domain localizes only at spindle poles (C') in mud3/mud4 mitotic follicle cells and fails to rescue spindle orientation (D E). Statistical significance in spindle orientation was determined using the Mann-Whitney test.",
    "ncbi_link": "mud: 44839"
  },
  {
    "caption": "D-F. Random spindle orientation in pinsp62/pinsp62 null mutant follicle cells is rescued by the expression of full-length Pins or Pins-myr-GFP. Representative pictures (D, E) and quantification (F) are shown. Scale bars = 5 microns. Statistical significance in spindle orientation was determined using the Mann-Whitney test. **** p<0.0001.",
    "ncbi_link": "pins: 53569"
  },
  {
    "caption": "A. Spindle orientation is randomized in Dlg1P20/Dlg1P20 and Dlg1P20/Dlg2 mutant follicle cells. B. Random spindle orientation in pinsp62/pinsp62 null mutant follicle cells is rescued by the expression of full length Pins or phosphomimetic (S436D) Pins. Unphosphorylatable (S436A) Pins fails to rescue. C. Quantification of spindle orientation phenotypes. Statistical significance in spindle orientation was determined using the Mann-Whitney test. **** p<0.0001, *** p<0.001. D.",
    "ncbi_link": "Dlg: 32083
pins: 53569
Pins: 53569"
  },
  {
    "caption": "H. Quantification of spindle orientation phenotypes in the Stage 9/10 embryonic ectoderm. n = 17 cells from 2 embryos in w1118 and n = 18 cells from 2 embryos in Dlg1P20/Dlg2 embryos. Statistical significance in spindle orientation was determined using the Mann-Whitney test. ** p=0.0015.",
    "ncbi_link": "Dlg: 32083"
  },
  {
    "caption": "A-C. Multiple genetic approaches were used to test a role for either Khc73 or GUKHolder in metaphase spindle orientation. Representative pictures (A-B) and quantification (C) are shown. Scale bars = 5 microns. Spindle angle randomization in pinsp62/pinsp62 null mutant follicle cells is included as a positive control for comparison.",
    "ncbi_link": "GUKHolder: 53563
Khc73: 36718
pins: 53569
p62: 35246"
  },
  {
    "caption": "A-D. Two distinct patterns of Inscuteable localization are observed in the follicular epithelium when UAS-Inscuteable is driven by Traffic jam-GAL4. (A, C) In the first pattern (InscA), Inscuteable is highly enriched at the apical cell surface. (B, D) In the second pattern (InscB), Inscuteable is observed at both the lateral and apical cortex. Mud and Pins localizations are also shown. Representative pictures (A, B) and quantifications (InscA: average of 5 cells, InscB: average of 7 cells) (C, D) are shown.",
    "ncbi_link": "GAL4: 855828"
  },
  {
    "caption": "E. aPKC localization in InscA and InscB follicle cells. F. Quantification of spindle orientation phenotypes shows that mitotic spindles are reoriented in InscA cells, but not InscB cells. Reorientation relies on Mud but not on the interaction between Pins and Dlg. G",
    "ncbi_link": "Dlg: 32083
Mud: 44839
Pins: 53569"
  },
  {
    "caption": "A. Confocal microscopy image of PD myotubes (cl. 3LE8) infected for 72 h with adenovirus containing TFEB (PD + Ad-TFEB 72 h) shows a dramatic reduction in the number of large LAMP1-positive lysosomes (red) compared to that in untreated (PD) or adenovirus (PD + Ad-null)-treated PD myotubes. WT myotubes are shown on the left panel. Nuclei are stained with Hoechst (blue). TFEB was detected with anti-Flag antibody (green).B. Distribution of lysosomal size differs significantly in Ad-null and Ad-TFEB PD myotubes (p = 6.32 × 10−8; Kolmogorov-Smirnov test). Lysosomal size is expressed as number of pixels representing lysosomal area (LAMP1-positive structures). The median lysosomal size of Ad-TFEB infected myotubes (m = 367.13 pixels, n = 703, range 208-2659) was significantly lower than that of Ad-null infected myotubes (m = 491.16 pixels, n = 1395, range 200-2857; p = 6.5 × 10−12; Wilcoxon rank sum test).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "C. Confocal microscopy image of PD myotubes infected for 24 h with Ad-TFEB shows relocation of lysosomes to the plasma membrane (top). Images showing LAMP1 staining (red) on plasma membrane in a PD myotube infected with Ad-TFEB (bottom; arrows) but not in a non-infected cell (middle). Non-permeabilized cells were incubated with anti-LAMP1 antibody at 4°C for 40 min, followed by fixation and staining with secondary antibody.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "D. Confocal microscopy images of live non-infected PD myotubes (left) or PD myotubes infected for 72 h with Ad-TFEB (right) show a dramatic reduction in the amount of accumulated glycogen in TFEB-treated cells. The cells were incubated with the fluorescent glucose (2-NBDG; green), extensively washed, and analysed by confocal microscopy. Bar: 10 µm for all panels.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "Confocal microscopy of live unstained fibres from a GFP-LC3:WT mouse (WT) and from untreated (GAA−/−) or ERT-treated (GAA−/−; +ERT) GFP-LC3:GAA−/− mice. Images show typical centrally located autophagic build-up with multiple clusters of LC3-positive autophagosomes. Structures like these are never seen in WT muscle. Autophagic build-up is present virtually in all fibres derived from EDL or gastrocnemiusmuscles (not shown), but only in 60-70% of FDBfibres. Labelled recombinant human GAA (red) was administered i.v. into 3-4 month-old GFP-LC3:GAA−/− mice (n = 5) at a dose of 100 mg/kg twice with a 24 h interval. Mice were sacrificed the next day, and live fibres (shown for EDLmuscle) were analysed by confocal microscopy. The labelled recombinant GAA was detected almost exclusively in the autophagic vesicles. At least 500 fibres were analysed for each condition. Bar: 10 µm.",
    "ncbi_link": "GAA: 14387
GAA: 2548"
  },
  {
    "caption": "A. Immunostaining of non-infected cells (day 13 in differentiation medium) and cells infected with a mutant form of TFEB (TFEBmt) with LAMP1 (red) and Flag (green). Ad-TFEBmt was added to the myotubes for 72 h on day 10 in differentiation medium. Ad-TFEBmt-infected cells show massive accumulation of TFEB in the nuclei and significant reduction in lysosomal size, similar to that seen with TFEB.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "B. Western blot of cell lysates confirms the presence of TFEB in the nuclear fraction; the different intensities of the two bands corresponding to LAMP1 protein in untreated and TFEBmt-treated samples may reflect the differences in the glycosylation pattern.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "C. Western blot of protein lysates from untreated, Ad-null, TFEB, and TFEBmt-treated myotubes with anti-caspase-3 antibody. No activated (cleaved) products are detected in any condition. α-Tubulin was used as a loading control.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "D. TUNEL assay shows the presence of some apoptotic cells in Ad-TFEB-infected cultures, but not in control cultures infected with adenovirus alone (n = 3). Bar: 10 µm for all panels.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "A. Confocal microscopy images of live fibres derived from 3 to 4 month-old GFP-LC3:WT (top left), untreated GFP-LC3:GAA−/− (bottom left) or TFEB-treated GFP-LC3:GAA−/− (right) mice. All fibres were transfected with mCherry-LAMP1 to visualize lysosomes (red). The effects of TFEB are clearly visible - overall reduction in lysosomal size, appearance of normal size lysosomes (similar to those in the WT), and lysosomal docking to the plasma membrane (inset). Bar: 10 µm.",
    "ncbi_link": "GAA: 14387
TFEB: 21425"
  },
  {
    "caption": "B. FDBmuscle of a GAA−/− mouse was transfected with both GFP-TFEB and mCherry-LAMP1 (GAA−/− + GFP-TFEB). Images were taken before (left) and after 4 h (right) of time-lapse microscopy. Lysosomal clearance is visible in the TFEB-transfected fibre at both time points. Lysosomes appear to \"exit\" the fibre (inset and arrow) at the 4 h time point when TFEB is activated as evidenced by its nuclear translocation (green nuclei). Bar: 10 µm.C. The mean maximum velocity of lysosomes (top) and the number of large (>3.5 µm) lysosomes (bottom) in untreated and TFEB-treated PD fibres (note: all data for Flag- and GFP-TFEB-treated fibres are pooled). Lysosomal velocities were calculated from time-lapse images using ImageJ software with the manual tracking plug-in. For each condition the trajectories of multiple lysosomes were followed (n = 26 untreated; n = 43 TFEB-treated) and the three highest velocity measurements per lysosome were recorded. In TFEB-treated fibres, the maximum velocity of lysosomes was significantly increased (p = 2.07 × 10−17) and the number of large lysosomes was significantly decreased (p = 1.0 × 10−3). Ten untreated and 24 TFEB-treated fibres were analysed for the size calculations. * indicates statistically significant differences (p ≤ 0.001; Student's t-test). Error bars represent 95% confidence intervals.",
    "ncbi_link": "GAA: 14387
TFEB: 21425"
  },
  {
    "caption": "Confocal microscopy images of live fibres from GFP-LC3:GAA−/− mice.Muscle was transfected with mCherry-LAMP1 only. The image (a single frame from the time-lapse series presented in Movie 5) shows lysosomes (red), LC3-positive autophagosomes (green) and a number of autolysosomes (yellow).Muscle was transfected with Flag-TFEB and mCherry-LAMP1. Massive formation of autolysosomes is indicated by yellow structures; the three lower panels provide a snapshot of the process of exocytosis. The structures at the plasma membrane are labelled with both LC3 and LAMP1, indicating that they represent amphisomes (a product of fusion between autophagic vesicles and late endosomes) or autolysosomes (a product of fusion between autophagic vesicles and lysosomes). Bar: 10 µm for all panels.",
    "ncbi_link": "GAA: 14387
TFEB: 21425"
  },
  {
    "caption": "Confocal microscopy images of live fibres from muscle-specific autophagy-deficient GAA−/− mice (Atg7:GAA DKO).Muscle was transfected with mCherry-LAMP1 only.Muscle was transfected with GFP-TFEB and mCherry-LAMP1 (Atg7:GAA DKO +GFP-TFEB). The TFEB-transfected fibres show realignment of the lysosomes and membrane detachment (most striking in top and bottom panels) similar to those in TFEB-transfected fibres from PD mice (see Fig 4B inset). Lysosomes can be seen in the space between the fibre and plasma membrane (arrows). Bar: 10 µm for all panels.The mean maximum velocity of lysosomes (top) and the number of large (>3.5 µm) lysosomes (bottom) in untreated and TFEB-treated autophagy-deficient Atg7:GAA DKO fibres. The increase in maximum velocity (41%) is significant (p = 2.729 × 10−18; n = 57 lysosomes for untreated; n = 52 lysosomes for TFEB-treated), but there is only a slight trend toward smaller lysosomal size (p = 7.0 × 10−2; n = 10 fibres for untreated; n = 21 fibres for TFEB-treated). The corresponding values from GAA−/− mice are presented for comparison (for TFEB-treated condition: n = 19 lysosomes for velocity measurements, and n = 10 fibres for the lysosomal size measurements). * indicates statistically significant differences (p ≤ 1.0 × 10−5 for the top panel and p ≤ 0.01 for the lower panel; Student's t-test).",
    "ncbi_link": "Atg7: 74244
GAA: 14387
TFEB: 21425"
  },
  {
    "caption": "A. Glycogen assay in TFEB-injected gastrocnemii and in the contralateral muscles. In TFEB-injected musclesglycogen levels were significantly decreased compared to those in untreated muscles. * indicates statistically significant differences (p = 1.0 × 10−4; n = 6; Student's t-test).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "B. PAS staining of TFEB-treated muscle shows a reduction of lysosomalglycogen stores (puncta) compared to those in untreated muscle. Original magnification: 20×.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "C. LAMP1 staining of TFEB-injected gastrocnemii and of the contralateral untreated muscles. In TFEB-treated muscles, the size of LAMP1-positive vesicles was reduced. Bar: 2 µm.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "A. EM images of muscle injected with either AAV-GFP (untreated) or AAV-TFEB (TFEB-treated). Asterisks indicate glycogen-containing lysosomes. Bar: 1.5 µm (upper panels) and 0.45 µm (lower panels). Higher magnification images (lower panels) show that glycogen particles are less densely packed in TFEB-treated muscle. Black arrows indicate autophagosome profiles; the white empty arrow shows remnants of mitochondria engulfed by the lysosome.B. Graphical presentations of lysosomal length (average ± SE; n = 100 lysosomes; p = 6.31 × 10−5), the number of lysosomes per 5 µm2 area of muscle fibre section (average ± SE; n = 50 fields; p = 4.80 × 10−3), and the number of autophagosomes flanking glycogen-containing lysosomes (average ± SE; n = 100 lysosomes; p = 4.39 × 10−5 < 0.001). Student's t-test was used for each comparison.C. Graphical presentations of mitochondrial size (average ± SE; n = 100) and the number of mitochondria per 5 µm2 area of muscle fibre section (average ± SE; n = 50 fields). The differences were not significant by Student's t-test (p = 3.65 × 10−1 and 4.27 × 10−1, respectively).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(B) Relative transcript expression of Fibronectin, (C) Collagen I and (D) Collagen III to GAPDH.",
    "ncbi_link": "GAPDH: 
Collagen I: 1277
Collagen III: 1281
Fibronectin: 2335"
  },
  {
    "caption": "Relative expression of Slug mRNA (B) normalized to GAPDH in PF and PF-PH patients.",
    "ncbi_link": "GAPDH: 
Slug: 6591"
  },
  {
    "caption": "(E) Relative CD68 mRNA expression normalized to GAPDH",
    "ncbi_link": "GAPDH: 
CD68: 968"
  },
  {
    "caption": "Relative expression of Prolactin-induced protein (PIP) mRNA (D) normalized to GAPDH in PF and PF-PH patients.",
    "ncbi_link": "GAPDH: 
PIP: 5304
Prolactin-induced protein: 5304"
  },
  {
    "caption": "Quantification of (B) fibronectin, (C) Collagen I and (D) Collagen III mRNA.",
    "ncbi_link": "Collagen I: 29393
Collagen III: 84032
fibronectin: 25661"
  },
  {
    "caption": "Relative expression of fibronectin (I), collagen I (J) and collagen III (K) mRNA normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
collagen I: 29393
collagen III: 84032
fibronectin: 25661"
  },
  {
    "caption": "Relative expression of Slug mRNA (B) normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
Slug: 25554"
  },
  {
    "caption": "(E) CD68 mRNA quantification in Bleo and Bleo-MCT rats",
    "ncbi_link": "CD68: 287435"
  },
  {
    "caption": "Relative expression of PIP mRNA (A) normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
PIP: 64673"
  },
  {
    "caption": "Relative expression of Slug mRNA (C) normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
Slug: 25554"
  },
  {
    "caption": "(D) right ventricular systolic pressure (RVSP) and (E) right ventricular hypertrophy index in PF-PH rats treated with Si-Slug compared to Si-Scrm.",
    "ncbi_link": "Slug: 6591"
  },
  {
    "caption": "Relative expression of fibronectin (F), Collagen I (G) and Collagen III (H) normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
Collagen I: 29393
Collagen III: 84032
fibronectin: 25661"
  },
  {
    "caption": "(B) Relative expression of CD68 mRNA normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
CD68: 287435"
  },
  {
    "caption": "Relative expression of PIP mRNA (D) normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
PIP: 64673"
  },
  {
    "caption": "(A-F) Representative PAS-stained sections of the pons  (A) and hippocampal (C) regions of the brain and heart (E) of one year old HOIL-1[C458S] and WT  mice are shown. Scale bar = 100 μm. Arrow heads indicate  α-amylase-resistant   PAS-positive   polyglucosan deposits. Graphs showing  α-amylase resistant  PAS  scores of the  pons (B) and  hippocampal  (D) regions of the  brain and the  heart (F) of HOIL-1[C458S] (red) and WT (blue) mice aged 0.5, 1.0 and 1.5 years. The number of biological replicates analysed at each age is indicated. The word zero highlighted in blue indicates that no α-amylase resistant, PAS-positive material could be detected in the WT  mice. The error bars show mean + SEM. Statistical significance between the genotypes was calculated by using two-way ANOVA and Šidák's multiple comparison's test. **** denotes p<0.0001.",
    "ncbi_link": "HOIL-1: 24105"
  },
  {
    "caption": "(B) Mean±SEM fluorescence intensities of wild-type and NLxxxL motif mutant Far1(1-150)-GFP in either wild-type or clb5(hpm) clb6(hpm) strain over the cell cycle.",
    "ncbi_link": "clb5: 856237
clb6: 853003"
  },
  {
    "caption": "(F) Pheromone sensitivity halo assay with PGAL1-3HA-CLB5 sic1Δ strains carrying either wild-type FAR1, far1Δ, far1(L135A) or far1(RxL). Different concentrations of α-factor were pipetted on the paper discs. On glucose plates, α-factor triggers cell cycle arrest. CLB5 overexpression from PGAL1 in sic1Δ strain causes lethality presumably by inhibition of replication licensing, which is rescued by the presence of α-factor, which leads to Far1-depedent inhibition of excess Clb5-Cdk1 activity. The experiment was repeated twice, a representative example is shown.",
    "ncbi_link": "HA: 
CLB5: 856237
FAR1: 853283
far1: 853283
GAL1: 852308
sic1: 850768"
  },
  {
    "caption": "(A) Dot plot depicting the expression of mRNA for neurogenic transcription factor MEIS2 in prospectively isolated cellular populations from the SEZ.",
    "ncbi_link": "MEIS2: 17536"
  },
  {
    "caption": "(B) Micrographs depicting the expression of neurogenic fate determinant Meis2 mRNA and MEIS2 protein in acutely dissociated SEZ cells. Note that Meis2 mRNA positive LRCs have low (no) MEIS2 protein.",
    "ncbi_link": "Meis2: 17536"
  },
  {
    "caption": "(F) Dot plot depicting the expression of miR-204 in prospectively isolated cells of neural lineage.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(A) Micrographs of in situ hybridization for miR-204 in an adult mouse brain section. (A' and A'') are magnifications of boxed areas in (A or A'), respectively.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(B) Dot plot showing miR-204 levels in ChP and SEZ in the adult mouse brain measured by RT-qPCR. (C) Agarose gel of RT-qPCR product loaded after the saturation phase showing presence of miR-204 and U6 in mouse ChP, SEZ and CSF.",
    "ncbi_link": "miR-204: 387200
U6: RF00026"
  },
  {
    "caption": "Plots depicting the miR-204 levels (E) in EVs and EV-free CSF (n=2). (F) Agarose gel of RT-qPCR analysis depicting levels of miR-204 in the EV-free supernatant and EV containing fraction of human CSF loaded at the saturation phase.",
    "ncbi_link": "miR-204: 406987"
  },
  {
    "caption": "(G) Micrographs of transmission electron microscopy imaged extracellular vesicles (EVs) isolated from sham treated (upper row) and GW4869 treated animals (lower row). (G'' and G''') are magnifications of boxed areas in overview images to the left. (H) Dot plot depicting miR-204 levels in the CSF isolated 2 h after the ventricular injection of GW4869 inhibitor.",
    "ncbi_link": "miR-204: 406987"
  },
  {
    "caption": "(A) Gel pictures of the saturation phase of RT-qPCR analysis for miR-204 in SEZ primary culture cells, ChP co-culture and ChP explants 7 day post preparation.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(B) Gel electrophoresis of RT-qPCR analysis loaded at the saturation phase for miR-204 in SEZ culture medium and SEZ medium from the ChP co-culture.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(B, C) Micrographs depicting specific expression of AAV5 encoded GFP in the ChP 7 days after viral delivery in the lateral ventricle. (B' and C') are magnifications of the SEZ and (B'' and C'') of the ChP. (D) Dot plot depicting expression of miR-204 in ChP 7 days after second ventricular injection of AAV5 encoding for miR-204-specific TuD compared to scrambled control. ",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "Micrographs depicting immunoreactivity for MEIS2 (E, F) priming factors in the LRCs (BrdU+ only) 7 days after ChP-specific miR-204 inhibition and scrambled control White arrows point out the primed LRCs, the arrowheads label the MEIS2 Dot plots depicting the proportion of LRCs immunoreactive for the priming proteins MEIS2 after ChP specific miR-204 interference.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "Micrographs depicting immunoreactivity for MCM6 (H, I) priming factors in the LRCs (BrdU+ only) 7 days after ChP-specific miR-204 inhibition and scrambled control White arrows point out the primed LRCs, the arrowheads label the MCM6+ LRCs. Dot plots depicting the proportion of LRCs immunoreactive for the priming proteins MCM6 (J) after ChP specific miR-204 interference.",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(K, L) Micrographs showing the cellular composition in the SEZ 7 days after injection of AVV5 encoding for scrambled control (K) and miR-204 specific TuD (L). Note the reduction of primed LRCs (BrdU+ only, white arrows in K and L) upon TuD-204 injection. (M) Dot plot depicting the number of LRCs (BrdU+ only) in the SEZ 7 days after miR-204 inhibition. ",
    "ncbi_link": "miR-204: 387200"
  },
  {
    "caption": "(B) USH1C transcripts were consistently detected in all tested organs of WT and USH1C pigs, except in the heart and cerebellum. RT-PCR for GAPDH was used as control (Ctrl.).",
    "ncbi_link": "GAPDH: 396823
USH1C: 100514274"
  },
  {
    "caption": "(D) Representative Western blot analysis proved lack of harmonin protein expression in retina and duodenum of USH1C pigs at the age of 3 weeks (3w) (1 piglet, 1 retina, 1 duodenum) and 1 year (1y) (2 pigs, 1 retina each, 3 TRs). Arrow indicates the expected size of harmonin isoform a (72kDa).",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(E) Representative immunofluorescence staining of harmonin (green) of longitudinal cryosection through WT and USH1C pig retinas (2 pigs, 1y, 1 retina each, 3 TRs, scale bar 10µm) demonstrated the absence of harmonin staining in the outer segment (OS) of photoreceptor cells and in the other layers below the outer limiting membrane (OLM, arrow) of the USH1C pig retina.",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(A, B) Upregulation of GFAP in the retina of USH1C pigs at an age of 3 weeks (3w). (A) Representative immunofluorescence staining of GFAP in Müller glia cells which extend throughout almost the entire retina from the OLM (arrow) to the ganglion cell layer (GCL) of the retina. The consistent increase of GFAP expression in the Müller glia of USH1C pigs indicates Müller cell activation and gliosis. IS, inner segment; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; scale bar: 20 µm. (B) Left panel: Western blot analysis of GFAP protein expression in 3w old USH1C piglets and age matched controls. Anti-actin Western blot was used as loading control. Right panel: Quantification of Western blot bands in 4 gels by the LI-COR Odyssey system revealed a strong increase GFAP expression in 3w USH1C piglets when compared to age-matched WT controls (2 piglets, 3w, 2 retinas each, 2 TRs, error bars represent standard deviation (SD) of the mean, two-tailed Student's t tests, *p<0.05).",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(C, D) Reduced synaptic width in USH1C pigs at an age of 1 year (1y). (C) Fluorescent microscopic analysis of the cone synapse phenotype. Left panel: Representative images of longitudinal sections through WT and USH1C pig retinae stained for the pre-synaptic marker PSD-95 (green) and by fluorescent peanut agglutinin (PNA, red) for cone synaptic pedicles (white arrows) and counter-stained by DAPI for nuclear DNA (blue). Scale bar 10µm. Middle panel: Higher magnification of a PNA-stained cone synaptic pedicle. Synapse width was determined as the maximum extension of consistent PNA signals. Scale bar 1µm. Right panel: Measuring cone synaptic pedicle width in WT and USH1C pigs by applying a Fiji script to PNA-stained sections indicated reduced synaptic width (2 pigs, 1y, 1 retina each, number of examined synapses indicated, error bars represent SD, two-tailed Student's t tests, ***p<0.001). (D) Determining cone synaptic pedicles width by TEM. Left panel: Representative images of retinal cross sections. Scale bar 500nm. Right panel: Quantification of synaptic width confirmed the significantly reduced width of cone synaptic pedicles in USH1C pigs. (1 pig, 1y, 1 retina each, number of examined synapses indicated,",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(A-C) Ciliary length measured by fluorescence microscopic analysis at 1 year of age (1y). (A) Representative immunostaining of the ciliary marker Gt335 (green) in longitudinal cryosections of PRC ciliary regions in WT and USH1C retinas. Counterstaining by DAPI, scale bar 10µm. (B) Gt335 staining at higher magnification and principle of quantifying ciliary length by Gt335 staining. Scale bar 500nm. (C) Length of connecting cilia (CC) appear elongated in USH1C when applying a Fiji script to immunostained histological sections (2 pigs, 1y, 1 retina each, number of examined connecting cilia is indicated, error bars represent SD, two-tailed Student's t tests, ****p<0.0001).",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(D, E) Measuring CC length in TEM sections. (D) Representative images of longitudinal cross sections and principle of determining CC length. Scale bar 500nm. (E) Elongation of CC length is confirmed in TEM sections of USH1C PRC. (1 pig, 1y, 1 retina each, number of examined connecting cilia indicated, error bars represent SD, two-tailed Student's t tests, ****p<0.0001).",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "Length of primary cilia in dermal fibroblasts. (F) Staining of ciliary structures in fibroblasts stained with ARL13B (ciliary shaft, green) and PCNT2 (ciliary base, red), DAPI (nucleus, blue). Scale bar upper panel 5 µm, lower panel 2.5 µm. (H) Similarly, ciliary length of fibroblasts from a human USH1CR31X/R80fs patient are elongated, compared to a healthy control (7 TR, number of cells examined indicated, KS-test, ****p<0.0001).",
    "ncbi_link": "USH1C: 10083"
  },
  {
    "caption": "(I-M) Outer segment (OS) PRC architecture by TEM of longitudinal retinal sections. (I) At 3w, WT show normal sub-cellular organization, including parallel stacking of photosensitive discs and calyceal processes (black arrows, representative image from 2 pigs, 2 retinas, scale bar 600nm). (J) In 3w USH1C rods, membrane discs appear also in vertical orientation (white arrows, representative image from 2 pigs, 2 retinas, scale bar 750nm). At 1y, interstitial gaps appeared in disc stacks of the OS in USH1C pigs (K, arrow, scale bar 550nm) and vesicles are found at the OS base (L, asterisk, scale bar 500nm). (M) The disc architecture in 1y animals was substantially distorted (arrows, representative image from 2 pigs, 2 retinas, scale bar 850nm).",
    "ncbi_link": "USH1C: 100514274"
  },
  {
    "caption": "(D) Efficacy of AAV gene therapy was examined in vivo by sub-retinal injection of Anc80 virus capsid expressing harmonin_a1 under a ubiquitous promoter into a USH1C pig (see also Figure EV5). Left panel: Sub-retinal injection reconstituted harmonin expression in the AAV-treated eye but not in the sham-treated eye (3 TR). Protein extract from a WT retina served as positive control, actin staining as loading control. The 72kD band correlates with harmonin_a isoforms while higher MW indicates putative dimer formation. Middle panel: Immunofluorescence reveals absence of harmonin in the retina of the PBS-injected control eye and harmonin abundance (green) in the retina of the AAV-treated eye. (Representative image from a single animal. Blue: DAPI, scale bar 25 µm). Right panel: Photopic gfERG reveal increased a- and b-wave response to single flash and flicker stimulation in the AAV-treated (red), compared to the sham-treated (black) eyes of two USH1C pigs.",
    "ncbi_link": "harmonin_a: 10083
harmonin_a1: 10083
USH1C: 100514274"
  },
  {
    "caption": "HDAC6 KO MEF cells are defective in aggregate clearance but not in autophagosome induction or targeting. (A) Filter‐trap analysis of MG132‐induced, SDS‐insoluble ubiquitinated aggregates generated in wild‐type (WT), HDAC6 KO, and KO MEFs reconstituted with different HDAC6 constructs as indicated. The signal intensity from the ubiquitinimmunoblot (bottom panel) was quantified and presented as the average of the means from three independent experiments along with the standard deviation (top). Note the significant accumulation of ubiquitin‐positive aggregates in HDAC6 KO MEFs and KO MEFs stably expressing HDAC6‐CD and ΔBUZ mutants. WT, HDAC6 KO, and HDAC6 KO MEFs stably expressing human HDAC6 (hHDAC6 WT), HDAC6 CD (catalytically inactive mutant), or HDAC6 ΔBUZ (ubiquitin‐binding‐deficient mutant) were analysed for the level of HDAC6 using an anti‐human HDAC6 antibody. Mouse endogenous HDAC6 (mHDAC6) and actin levels were determined by each corresponding antibody.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(B) WT and HDAC6 KO MEFs were treated with MG132 and subjected to Western blot analysis for LC3, actin, and HDAC6.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(D) WT and ATG5 KO MEFs are treated with 2.5 μM MG132 for 1 day and incubated with normal growth media for 18 h. MEFs are immunostained with anti‐LC3 (red) and anti‐ubiquitin antibody (green).",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(A) Wild‐type and HDAC6 KO MEFs were transfected with pcDNA, pcDNA‐HDAC6WT, HDAC6CD, or HDAC6ΔBuz, along with mCherry‐GFP‐LC3 as indicated. Yellow signals indicate non‐acidic autophagosomes and red signals indicate acidic autophagolysosomes. Scale bar, 10 μm.",
    "ncbi_link": "HDAC6: 15185
LC3: 66734"
  },
  {
    "caption": "(C)In vitro fusion assays. Autophagosomes (APGs) and lysosomes (Lys) purified from wild type and HDAC6−/− MEFs were subjected to heterotypic and homotypic in vitro fusion assays (representative fields are shown in Supplementary Figure S3). Values are means+s.e. of the percentages of fusion from three independent experiments (more than 10 images per each experiment).",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(D) EM images of wild‐type and HDAC6 KO MEFs in normal growth conditions. Yellow arrows, autophagosomes; red arrows, autophagolysosomes; green arrowheads, multilamellar bodies.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(A) Autophagosome-lysosome fusion is analysed in wild‐type and HDAC6 KO MEFs with or without starvation (6 h) using mCherry‐GFP‐LC3 as described in Figure 2A.",
    "ncbi_link": "HDAC6: 15185
LC3: 66734"
  },
  {
    "caption": "(B) Wild‐type and HDAC6 KO MEFs were cultured in Hank's solution for 3 h followed by immunoblotting with an antibody for LC3, HDAC6, and GAPDH.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(C) Long‐lived protein degradation in wild‐type and HDAC6 KO MEF cells. The degradation of [14C]‐valine labelled long‐lived protein was measured in the presence or absence of 3‐methyl adenine (3MA, inhibits the formation of autophagic vacuoles). The average of percentage degradation from three independent experiments is presented. The error bar represents the standard deviation.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(A) Wild‐type and HDAC6 KO MEFs were treated with MG132 and immunostained with antibodies to Lamp‐1 (a lysosome marker, red) and ubiquitin (green) as indicated. F‐actin was detected by phalloidin (blue). The arrows indicate ubiquitin‐positive aggregates that are surrounded by F‐actin and Lamp‐1.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(B, C) Wild‐type and HDAC6 KO MEFs were transfected with mCherry‐GFP‐LC3, followed by treatment with LatA (100 nM) or nocodazole (250 nM) for 6 h and analysed as described in Figure 3A.",
    "ncbi_link": "HDAC6: 15185
LC3: 66734"
  },
  {
    "caption": "(F) Autophagosomes (APGs) and lysosomes (Lys) isolated from HDAC6 KO MEFs were treated or not with latrunculin (LatA) as indicated and subjected to in vitro fusion assay.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(A) Biochemical characterization of autophagic compartments isolated from HDAC6 KO cells. Different subcellular fractions (75 μg protein) isolated from the wild type (WT) were subjected to SDS-PAGE and immunoblotting for the indicated proteins. Hom, homogenate; APG, autophagosomes; APL, autophagolysosomes; Lys, lysosomes.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(C) WT and ATG5 KO MEFs were treated with MG132 and immunostained with antibodies to ubiquitin (green) as indicated. F‐actin was detected by phalloidin (red). The arrows indicated ubiquitin‐positive protein aggregates.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "(A) Wild‐type and HDAC6 KO MEFs were treated with MG132 and immunostained with antibodies against cortactin (red), ubiquitin (green), and phalloidin for F‐actin (blue) as indicated. The arrows indicated ubiquitin‐positive aggregates that were colocalized with F‐actin and cortactin.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(B) Wild‐type MEFs were transfected with control or cortactin siRNA, treated with MG132, and stained with antibodies for Lap‐1 (red, to label lysosome), or ubiquitin (green) and phalloidin for actin (blue). Note that F‐actin staining at protein aggregates was lost, but lysosomes remained concentrated in cortactin knockdown cells (arrow).",
    "ncbi_link": "cortactin: 13043"
  },
  {
    "caption": "(C) Wild‐type MEFs were transfected with control or cortactin siRNA, treated MG132 2.5 μM for 18 h, and subjected to filter‐trap assay using a ubiquitin antibody. The knockdown level of endogenous cortactin was confirmed by immunoblotting using an antibody against cortactin and GAPDH in the right panel.",
    "ncbi_link": "cortactin: 13043"
  },
  {
    "caption": "(D) U2OS cells were transfected with control siRNA and cortactin siRNA. Autophagosome-lysosome fusion was analysed with or without starvation (6 h) using the mCherry‐GFP‐LC3 reporter as described in Figure 3A.",
    "ncbi_link": "cortactin: 13043
LC3: 66734"
  },
  {
    "caption": "(E) The mCherry‐GFP‐LC3 plasmid was cotransfected with wild type, 9KQ (acetylation‐mimic), or 9KR (deacetylation‐mimic) cortactin‐expressing plasmids into wild‐type MEFs. Autophagosome-lysosome fusion was analysed as described in Figure 3A.",
    "ncbi_link": "cortactin: 13043
LC3: 66734"
  },
  {
    "caption": "(A) HDAC6 KO mice accumulate ubiquitin‐positive protein aggregates in the brain. The hippocampus and cerebral cortex regions from 6‐month‐old wild‐type and ubiquitin KO littermates were subjected to immunostaining with a ubiquitin antibody and counterstained with hematoxylin. The red arrows indicate ubiquitin‐positive neuritic aggregates and black arrows indicate cytoplasmic aggregates. These ubiquitin‐positive structures were rarely observed in control littermates. Scale bar, 50 μm",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(B) Apoptotic cell death in the cortex and hippocampus region of HDAC6 KO mice as determined by TUNEL staining. Apoptotic cells were only observed in HDAC6 KO mice. Scale bar, 100 μm.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(C) HDAC6 depletion in the Drosophila eye leads to ubiquitin‐positive pathology. Immunostaining for ubiquitin (green) in frontal eye sections of 1‐day‐old (d1) and 30‐day‐old (d30) fly eyes. The eyes of HDAC6‐depleted flies (GMR:GAL4/UAS‐HDAC6RNAi) developed ubiquitin‐ positive cytoplasmic inclusions that become more prominent at day 30 (d30). Blue, DAPI.",
    "ncbi_link": "GAL4: 
HDAC6: 32461"
  },
  {
    "caption": "(D) Depletion of HDAC6 in the Drosophila eye leads to age‐dependent degeneration. Light micrographs (left) and corresponding Richardson‐stained frontal eye sections (right) of 1‐day‐old and 30‐day‐old fly eyes. The eyes of control flies (GMR:GAL4/+) and HDAC6‐depleted flies (GMR:GAL4/UAS‐HDAC6RNAi) show normal highly organized ommatidial array at day 1; 30‐day‐old control animals also show no defects, but 30‐day‐old HDAC6‐depleted flies show degeneration with disorganization of the ommatidial array and loss of normal eye architecture ( × 40 and × 80).",
    "ncbi_link": "GAL4: 
HDAC6: 32461"
  },
  {
    "caption": "(B) Relative mRNA levels of KLF10  in the livers  from NAFL  and NASH mice. n=5. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "(H) Spearman correlations between KLF10 expression   and NAS in liver  tissues from NAFL  and NASH patients  using GEO datasets (GSE48452). Left panel, n=32 (including 17 NAFL patients  and 15 NASH patients). Right panel, n=21 (including 6 NAFL  and 15 NASH patients). Data information: * P <0.05, ** P <0.01-. Results are shown as mean ± SD. Spearman's correlation H).",
    "ncbi_link": "KLF10: 7071"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (B) Protein levels  of KLF10  in the livers  (left) and its expression  was normalized to the β-actin (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (C) H&E staining  of liver  sections.",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (D) CD68 immunofluorescence staining  of liver  sections (left) and its quantitation (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (E) Body weight (BW), liver/body weight  ratio, serum AST   and ALT   levels, and hepatic TG  contents of two groups of mice. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (F) Sirius red staining  of liver  sections (left) and its quantitation (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (G) Relative mRNA levels of genes involved in the hepatic inflammation  and fibrosis. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (H) Protein levels of TNF-α  in the livers  (left) and its expression  was normalized to the β-actin  (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (J) Protein levels of KLF10  in the livers   (left) and its expression  was normalized to  β-actin (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (K) H&E staining  of liver  sections.",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (L) CD68 immunofluorescence staining  of liver sections (left) and its quantitation (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through tail vein  injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (M) Body weight (BW), liver/body weight  ratio, serum AST  and ALT  levels, and hepatic TG  contents. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (N) Sirius red staining  of liver  sections (left) and its quantitation (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein  injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (O) Relative mRNA levels of genes involved in the hepatic inflammation  and fibrosis. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "8-week-old male C57BL/6J mice  were administered with AAV-GFP  or AAV  -Klf10  through  tail vein injection, and then kept on HFD-feeding for 12 weeks. n=5 per group. (P) Protein levels of TNF-α in the livers  (left) and its expression  was normalized to the β-actin (right). Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "GFP: 
Klf10: 21847"
  },
  {
    "caption": "(A) Heatmap of genes in mouse primary hepatocytes  transfected with lentivirus  vectors expressing KLF10  (KLF10OE) or empty vector (Ctrl), P＜0.001. n=5 per group. The color gradient represents log2(Fold change).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "(B) Relative mRNA (n=5) and protein (n=3) levels of zDHHC7  in MPHs  expressing KLF10  or empty vector (Ctrl). The protein level of KLF10  or zDHHC7  was normalized to  β-actin. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test (B",
    "ncbi_link": "KLF10: 21847
zDHHC7: 102193"
  },
  {
    "caption": "(C-D) Spearman correlations between KLF10  and zDHHC7  in liver  tissues from NASH  and NAFL patients  using GEO datasets (GSE48452 and GSE61260). In the dataset GSE61260 (C), n=83 (including 38 healthy controls, 21 NAFL patients  and 24 NASH patients). In the dataset GSE48452 (D), n=73 (including 41 healthy controls, 17 NAFL patients  and 15 NASH patients). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Spearman's correlation (C, D).",
    "ncbi_link": "KLF10: 7071
zDHHC7: 55625"
  },
  {
    "caption": "(E) Relative mRNA levels of DHHCs family in HepG2  cells overexpressing KLF10  or empty vector (ctrl). n=5. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "(H) The  transcriptional activity of wild-type or mutant zDHHC7  promoter in HepG2  cells. n=3. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "zDHHC7: 55625"
  },
  {
    "caption": "(I)  Chromatin immunoprecipitation  analysis of KLF10 binding  activity at the zDHHC7  promoter. Soluble chromatin  was prepared from the livers  of WD/CCl4  treatment-induced NASH mice  and immunoprecipitated  with antibodies against KLF10  or against IgG. The final DNA extractions were amplified using pairs of primers that cover the regions of zDHHC7  and GAPDH  gene promoters. (J) Quantitative real-time RCR results of ChIP  assays. IgG, immunoglobulin G. n=3. Results represent three independent experiments. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test J).",
    "ncbi_link": "GAPDH: 14433
zDHHC7: 102193"
  },
  {
    "caption": "The liver  tissues were collected from WD/CCl4-treated mice  expressing KLF10  or control (A) Representative immunofluorescence staining  of CD36  and β-catenin. The arrows represent the colocalization  of CD36  and  β-catenin.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from WD/CCl4-treated mice  expressing KLF10  or control (B) Quantitative results of CD36 colocalization  rate. n=5. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test (B",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from WD/CCl4-treated mice  expressing KLF10  or control (C) Expression  of CD36  in whole livers  and plasma membrane fractions.  Protein levels were normalized to the β-actin or ATP1a1, respectively. n=5. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from WD/CCl4-treated mice  expressing KLF10  or control (D) Protein levels  of palmitoylated CD36  in mouse livers. (E) Quantitative results of CD36 colocalization  rate. n=3. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test E,",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from HFD-fed mice  expressing KLF10  or control (F) Representative immunofluorescence staining  of CD36  and β-catenin. The arrows represent the colocalization  of CD36  and β-catenin.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from HFD-fed mice  expressing KLF10 or control (G) Quantitative results of CD36 colocalization  rate. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from HFD-fed mice  expressing KLF10  or control (H) Expression  of CD36  in whole livers  and  plasma membrane  fractions. Protein levels  were normalized to the β-actin or ATP1a1, respectively. n=5. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "The liver  tissues were collected from HFD-fed mice  expressing KLF10  or control (I) Protein levels  of palmitoylated CD36  in mouse livers. (J) Quantitative results of CD36 colocalization  rate. n=3. Results represent three independent experiments. Data information: * P < 0.05, ** P < 0.01, *** P < 0.001. Results are shown as mean ± SD. Student's t test J).",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "HepG2  cells were transfected with lentivirus  vectors expressing shRNA targeting KLF10  or negative control (Ctrl). n=3. Results represent three independent experiments. (A)  Protein level of KLF10, and its normalization to β-actin.",
    "ncbi_link": "KLF10: 7071"
  },
  {
    "caption": "HepG2  cells were transfected with lentivirus  vectors expressing shRNA targeting KLF10  or negative control (Ctrl). n=3. Results represent three independent experiments. (B) Protein levels of palmitoylated CD36. Data information: ** P < 0.01. Results are shown as mean ± SD. Student's t test (B",
    "ncbi_link": "KLF10: 7071"
  },
  {
    "caption": "HepG2  cells were transfected with lentivirus  vectors expressing shRNA targeting KLF10  or negative control (Ctrl). n=3. Results represent three independent experiments. (C) CD36 protein expression the plasma membrane fractions, and its normalization to ATP1a1. Data information: ** P < 0.01. Results are shown as mean ± SD. Student's t test C).",
    "ncbi_link": "KLF10: 7071"
  },
  {
    "caption": "HepG2  cells were treated with  2-BP and/or lentivirus  vectors expressing KLF10. n=3. Results represent three independent experiments. (D) Protein levels  of KLF10, and its normalization to   β-actin. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "HepG2  cells were treated with 2-BP and/or lentivirus  vectors expressing KLF10. n=3. Results represent three independent experiments. (E)  Protein levels  of palmitoylated CD36. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "HepG2  cells were treated with 2-BP  and/or lentivirus  vectors expressing KLF10. n=3. Results represent three independent experiments. (F) CD36 protein expression the  plasma membrane fractions, and its normalization to ATP1a1. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "HepG2  cells were treated with  2-BP and/or lentivirus  vectors expressing KLF10. n=3. Results represent three independent experiments. (G) BODIPY staining  showing the  lipid droplets.",
    "ncbi_link": "KLF10: 21847"
  },
  {
    "caption": "HepG2  cells were transfected with lentiviruses  expressing KLF10  and/or shRNA targeting zDHHC7. n=3 independent experiments. (H) Protein levels of KLF10  and zDHHC7, and its normalization to  β-actin. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847
zDHHC7: 55625"
  },
  {
    "caption": "HepG2  cells were transfected with lentiviruses  expressing KLF10  and/or shRNA targeting zDHHC7. n=3 independent experiments. (I)  Protein levels of palmitoylated CD36. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847
zDHHC7: 55625"
  },
  {
    "caption": "HepG2  cells were transfected with lentiviruses  expressing KLF10  and/or shRNA targeting zDHHC7. n=3 independent experiments. (J) Immunofluorescence staining  of CD36  and Na+/K+-ATPase (left), and the quantitation of CD36 colocalization  rate (right). Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "KLF10: 21847
zDHHC7: 55625"
  },
  {
    "caption": "HepG2  cells were transfected with lentiviruses  expressing KLF10  and/or shRNA targeting zDHHC7. n=3 independent experiments. (K) BODIPY staining  for  lipid droplets.",
    "ncbi_link": "KLF10: 21847
zDHHC7: 55625"
  },
  {
    "caption": "HepG2 cells were transfected with lentiviruses  expressing KLF10  and/or shRNA targeting zDHHC7. n=3 independent experiments. (L) Cellular  TG  contents. Data information: ** P < 0.01. Results are shown as mean ± SD. 1-way ANOVA , L).",
    "ncbi_link": "KLF10: 21847
zDHHC7: 55625"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (A) Protein levels of KLF10  and CD36  in the liver  (left), and their normalization to β-actin (right). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA (A",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (B) Representative immunofluorescence staining  of KLF10  and CD36  (left), and the quantitative results (right). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through tail vein  injection, and then kept on  WD/CCl4  for 12 weeks. n=5 per group. (C) H&E and Sirius red staining  of liver  sections. (D) Quantitative results of Sirius red staining. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (E)  Body weights and liver/body weight ratio. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through  tail vein  injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (F) Hepatic TG  contents. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  wild-type (WT) or knockout mice  (CD36KO) were administered with AAV-GFP  (Ctrl) or AAV-KLF10  (KLF10OE) through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (G) Serum AST  and ALT  levels. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "GFP: 
CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (A) Serum AST  and ALT  levels. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (B) Hepatic TG  contents. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (C) Body weights  and liver/body weight  ratio. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (D) H&E and Sirius red staining  of liver  sections (left), and quantitation of Sirius red staining  (right). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (E) Immunofluorescence staining  of CD36  and β-catenin. (F) Quantitation of CD36  positive area. (G) Co-localization rate of CD36  and β-catenin. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation  site mutant CD36, mutant-CD36  plus KLF10  through  tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (H) Protein levels of palmitoylated CD36  in mouse livers  (left), and its quantitative results (right). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "6-week-old male CD36  knockout mice  were administered with AAV-TBG-wildtype-CD36, wildtype-CD36  plus KLF10, palmitoylation site mutant CD36, mutant-CD36  plus KLF10  through tail vein injection, and then kept on WD/CCl4  for 12 weeks. n=5 per group. (I) CD36 protein expression in the plasma membrane fractions, and its normalization to  ATP1a1. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. 1-way ANOVA",
    "ncbi_link": "CD36: 12491
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (A-B)  Protein levels  of KLF10, zDHHC7  and  TNF-α (A), and their normalization to β-actin (B). Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (C)  Body weights. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male  KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (D) Liver weights  and liver/body weight ratio. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with  KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (E) Hepatic TG  contents. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male  KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (F) Serum ALT  and AST  levels. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with  KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (G) H&E staining  and  Sirius red staining  of liver  sections.",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with  KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male  KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (H) Quantitative results of  Sirius red staining. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (I) Immunofluorescence staining  of CD36  and β-catenin. The arrows represent the colocalization  of CD36  and β-catenin.",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (J) Quantitative results of co-localization  rate of CD36  and β-catenin. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with  KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (K) Protein levels of palmitoylated CD36  in mouse livers. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with  KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male  KLF10hep-/- mice  and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (L) CD36 protein expression in  plasma membrane fractions from mouse livers, and its normalization to  ATP1a1. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "Albumin-cre mice  were crossed with KLF10flox/flox to generate hepatocyte-specific KLF10  knockout mice  (KLF10hep-/-). Then, 8-week-old male KLF10hep-/- mice   and KLF10flox/flox were treated with WD/CCl4  for 12 weeks. KLF10flox/flox mice  were used as the control (Ctrl). n=5 per group. (M) Relative mRNA level of genes involved in the liver inflammation  and fibrosis. Data information: * P <0.05, ** P <0.01, *** P <0.001. Results are shown as mean ± SD. Student's t test",
    "ncbi_link": "Albumin: 11657
cre: 2777477
KLF10: 21847"
  },
  {
    "caption": "(A and B) Root length (averages ± SD, n ≥ 15) (A) and cell death staining of cotyledons and primary root tips (B) of Arabidopsis seedlings that were exposed to 100 nM Pep2 for 7 days, 2 days after germination. BAK1 (D416N) is a kinase-dead variant.",
    "ncbi_link": "BAK1: 829480"
  },
  {
    "caption": "(C) Root length (averages ± SD, n ≥ 15) of Arabidopsis seedlings that were exposed to 100 nM Pep2. (*, p < 0.05 in two-tailed tests compared to the differences (± Pep2) from the corresponding values of bak1-3 plants. Two independent experiments were combined for statistical analysis.)",
    "ncbi_link": "bak1: 829480"
  },
  {
    "caption": "(A) Scatter plots for log2 fold changes of gene expression in WT plants versus bak1-3 plants treated with Pep2 for 2 and 10 h. The regression of these scatter plots is indicated by the red lines.",
    "ncbi_link": "bak1: 829480"
  },
  {
    "caption": "(B) Hierarchical analysis of genes exhibiting a >2-fold change in expression level in bak1-3 plants after Pep2 application for 10 h in a whole-genome microarray analysis. Using Genevestigator v3, these genes were separately cross-referenced to public databases to show their expression responses to salicylate (SA), methyl-jasmonate (JA), or ethylene (ET).",
    "ncbi_link": "bak1: 829480"
  },
  {
    "caption": "(C and D) qRT-PCR analysis of defense-related genes in 10-day-old seedlings exposed to 0.5 µM Pep2 for 10 h. Data are averages (±SD) of three biological replicates. (*, p < 0.05 in two-tailed tests compared to the corresponding bak1-4 and bak1-3 values in C and D, respectively. Relative cycle threshold (Ct) values of two independent experiments were combined for statistical analysis.)",
    "ncbi_link": "bak1: 829480"
  },
  {
    "caption": "(A) qRT-PCR analysis of PROPEP genes in 10-day-old seedlings exposed to 0.5 µM Pep2 for 10 h. *, p < 0.05 in two-tailed tests compared to the corresponding WT values. Relative Ct values of two independent experiments with three biological replicates each were combined for statistical analysis.",
    "ncbi_link": "PROPEP: "
  },
  {
    "caption": "(B) Anti-GFP immunoblot analyses in seedlings challenged with Pst DC3000 (DC3000) and Pst DC3000 ∆hrcC (∆hrcC) for the indicated times.",
    "ncbi_link": "hrcC: 1183025"
  },
  {
    "caption": "(D) Trypan blue cell death staining of Arabidopsis seedlings challenged with Pst DC3000 or Pst DC3000 AvrRpm1 (AvrRpm1) for 48 h.",
    "ncbi_link": "AvrRpm1: "
  },
  {
    "caption": "(F) Anti-GFP immunoblot analysis for the extracellular fraction of the seedlings exposed to Pst DC3000 AvrRpm1 for 48 h. (B, C, E and F) Arrowheads and arrows indicate an apparently full-length and processed form of PROPEP3-Venus, respectively. Asterisks indicate cross-reactive bands. The positions of the molecular weight markers are shown on the left of the immunoblots.",
    "ncbi_link": "AvrRpm1: "
  },
  {
    "caption": "(D) qRT-PCR analysis of the PR1 gene in 4-week-old plants exposed to 1 µM flg22. Data are averages (±SD) of three biological replicates. (*, p < 0.05 in two-tailed tests compared to the corresponding WT values. Relative Ct values of four independent experiments were combined for statistical analysis.)",
    "ncbi_link": "PR1: 815949"
  },
  {
    "caption": "(D) HE staining of lesional skin sections from WT and Raptor cKO mice injected with LL37 or control vehicle (n=6 for each group). Scale bar: 50 μm. (E) Dermal infiltrating cells were quantified (n = 6 for each group) for each high power field (HPF). ",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "(F) The mRNA expression levels of Tnf-α, Il6, Mmp9 and Vegf in skin lesions (n = 6 for each group).",
    "ncbi_link": "Il6: 16193
Mmp9: 17395
Tnf-α: 21926
Vegf: 22339"
  },
  {
    "caption": "(A) The back skins of WT (Tsc2+/+) and Tsc2+/- mice were intradermally injected with LL37 or control vehicle (n=5 for each group). Pictures were taken on day 0.5, 2, 5, 8, 12 after the first LL37 injection. The mouse experiments were repeated for three times, and 5 mice were included in each group for each time. The results of a representative mouse experiment were displayed. Scale bar: 2 mm.",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "(A) The mRNA expression level of human cathelicidin (CAMP) in skin lesions from healthy individuals (n = 10) and patients with rosacea (n = 15). Data",
    "ncbi_link": "CAMP: 820
cathelicidin: 820"
  },
  {
    "caption": "(E) Primary human keratinocytes expressing TLR2 shRNAs or scramble shRNA were treated with FITC-labeled LL37 or sLL37 ± PKH26 for 30 min followed by PBS washed, then live cells were analyzed by fluorescent microscope. Scale bar: 50 μm.",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": "(G) The mRNA expression levels of NF-κB family of transcription factors (Nfκb1, Nfκb1, Rela and Relb) in mice skin lesions (n=6 for each group).",
    "ncbi_link": "Nfκb1: 18033
Rela: 5970
Relb: 19698"
  },
  {
    "caption": "(B) The mRNA expression levels of mouse chemokines (Cxcl11, Cxcl12, Ccl2 and Ccl3) in skin lesions (n=6 for each group).",
    "ncbi_link": "Ccl2: 20296
Ccl3: 20302
Cxcl11: 56066
Cxcl12: 20315"
  },
  {
    "caption": "(B) Quantification of SARS-CoV-2 infection. After the siRNA knockdown of each target, viral infection was quantified as mean log2 fold-change (log2FC) of the percentage of SARS-CoV-2+ cells relative to the mean of scrambled non-targeting siRNAs ("SCRAMBLED", green dots; accordingly the mean log2FC value of scrambled non-targeting siRNAs was normalized to zero). Predicted positive targets ("TARGETING", grey dots), predicted negative targets ("NEG", blue dots) and positive controls ("POS", red dots, including ACE2 and TMPRSS2) are all shown. Wilcoxon rank-sum test P value comparing the predicted positive targets to scrambled non-targeting siRNAs is given.",
    "ncbi_link": "ACE2: 59272
TMPRSS2: 7113"
  },
  {
    "caption": "(D) Representative fluorescence images from the siRNA assay showing SARS-CoV-2 infection (green channel, top row), cell number (blue channel, middle row) and merged (bottom row). Results for scrambled non-targeting siRNA as negative control (left column), knockdown of three predicted top metabolic targets (PIKFYVE, SLC16A10, and PIP5K1C, middle columns), and knockdown of positive control (ACE2, right column) are shown. Scale bar=10 μm.",
    "ncbi_link": "ACE2: 59272
PIKFYVE: 200576
PIP5K1C: 23396
SLC16A10: 117247"
  },
  {
    "caption": "D Survival of indicated mice presented as percent of total number of mice analyzed. n=60 (per genotype), median survival of TAZG197V mice is 24.5 weeks, Mantel-Cox test: p < 0.0001 * * * *.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "I Picrosirius red staining of histology sections of hearts from WT and TAZ mutant mice.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "J qPCR analysis of ANP (left) and BNP (right) from total mRNA isolated from heart lysates of 20-week-old mice. Mean ± SEM, n=5 for ANP, n=4 for BNP, unpaired t test: p < 0.05 *, p < 0.001 * * *",
    "ncbi_link": "ANP: 230899
BNP: 18158"
  },
  {
    "caption": "A Mass spectrometric analysis of Cardiolipin and Monolysocardiolipin in WT and TAZG197V mouse heart. Mean ± SEM, n=3, unpaired t test: p < 0.05 *, p < 0.01 * *.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "B Volcano plot of differentially expressed genes between 14-week-old WT and TAZG197V mice. X-axis denotes fold change in expression (log2 scale), y-axis denotes adjusted p-value (negative log10 scale) for the analyzed genes in the data (each dot represents one single gene). Blue and red dots represent genes significantly downregulated (DR) and upregulated (UR), respectively, in the TAZG197V mice compared to WT mice. The cut-offs used were: adjusted p-value < 0.05 and fold change > 1.15 or < -1.15. Non-significant (NS) genes are depicted in black. Selected genes involved in pathways relevant for the study are labelled in the plot.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "C Western blot steady state protein levels of CPT1B and CPT2. Values were normalized to β-tubulin in control and iTAZ iPSC-cardiomyocyte. Mean of WT values was set to 1. Mean ± SEM, n=5, unpaired t test: p < 0.05 *, p < 0.0001* * * *.",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "E Extracellular acidification rate of control and iTAZ iPSC-cardiomyocytes. Basal state and upon sequential addition of glucose, oligomycin and 2 deoxyglucose (2-DG). Right, quantification of glycolytic capacity. Mean ± SEM, n=6, unpaired t test: p < 0.001* * * *",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "A Ejection fraction from short axis expressed in %, B Fractional shortening in %, Mean ± SEM, n=15 (WT control); 4 (TAZG197V control); 9 (WT treated); 7 (TAZG197V treated), 2Way ANOVA: p < 0.05 *, p < 0.01 * *",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "F Gene expression addressed by qPCR of ANP (left) and BNP (right) in 24-week-old WT and TAZG197V mice heart upon 6-week treatment with A769662. Mean ± SEM, n=4, unpaired t test: ns (non-significant)",
    "ncbi_link": "ANP: 230899
BNP: 18158
TAZ: 66826"
  },
  {
    "caption": "G Quantification of steady state levels of AMPK normalized to beta tubulin in tissue lysates from 24-week-old WT and TAZG197V mice heart from untreated control or following a 6-week treatment with A769662. The mean of the WT values was set to 1. Mean ± SEM, n=7 (control); 5 (treated), unpaired t test: p < 0.01 * *",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "I Real time respirometry, oxygen consumption rate, of isolated heart mitochondria from 24-week-old TAZG197V mice, from untreated control or following a 6-week treatment with A769662, driven by palmitoyl/carnitine/malate/ADP. The OCR of the untreated WT samples was taken as 100%. Mean ± SEM, n=3, unpaired t test: p < 0.01 * *",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "(A) Histogram representing CD86 expression in 5.2+ vs 5.1+ pDC isolated from indicated MCMV-infected MBMC; grey, 5.2+ and 5.1+ pDC from CTR MBMC; red, 5.2+ Ifnar1-/- pDC isolated from Ifnar1-TST MBMC; purple, 5.1+ WT pDC isolated from Ifnar1-TST MBMC. Dotted line shows isotype control staining. One histogram representative of 6 animals from 3 independent experiments is shown.",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Results were expressed as 5.2/5.1 ratio of Mean Fluorescence Intensity (MFI) values for CD86 or of the percentages of IFN-I-producing cells obtained from MCMV-infected Black, CTR MBMC; red, Ifnar1-TST MBMC (red)",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Results were expressed as 5.2/5.1 ratio of Mean Fluorescence Intensity (MFI) values for CD86 or of the percentages of IFN-I-producing cells obtained from CpG-stimulated mice. Black, CTR MBMC; red, Ifnar1-TST MBMC (red) Data shown (mean±SEM) are from 2 pooled independent experiments each with at least 3 mice per group.",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Results were expressed as 5.2/5.1 ratio of Mean Fluorescence Intensity (MFI) values for CD86 or of the percentages of IFN-I-producing cells obtained from MCMV-infected Black, CTR MBMC pale blue, Ap3b1-TST MBMC. Data shown (mean±SEM) are from 2 pooled independent experiments each with at least 3 mice per group.",
    "ncbi_link": "Ap3b1: 11774"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Results were expressed as 5.2/5.1 ratio of Mean Fluorescence Intensity (MFI) values for CD86 or of the percentages of IFN-I-producing cells obtained from CpG-stimulated mice. Black, CTR MBMC pale blue, Ap3b1-TST MBMC. Data shown (mean±SEM) are from 2 pooled independent experiments each with at least 3 mice per group.",
    "ncbi_link": "Ap3b1: 11774"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Ratio of IL-12- and TNF-producing cells in pDC isolated from indicated MCMV-infected MBMC. Black, CTR MBMC; red, Ifnar1-TST MBMC (red) Data shown (mean±SEM) are from 2 pooled independent experiments each with at least 3 mice per group.",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "The expression of indicated markers was analyzed in 5.2+ vs 5.1+ pDC of each MBMC type. Ratio of IL-12- and TNF-producing cells in pDC isolated from indicated MCMV-infected MBMC. Black, CTR MBMC ; pale blue, Ap3b1-TST MBMC. Data shown (mean±SEM) are from 2 pooled independent experiments each with at least 3 mice per group.",
    "ncbi_link": "Ap3b1: 11774"
  },
  {
    "caption": " (D) qPCR for the expression of the indicated genes was performed on whole mRNA isolated from the spleen of indicated MCMV-infected MBMC. CTR MBMC (black) and Myd88-/- TST MBMC (dark green) were treated with isotype control (IC, square) or blocking α-IFNAR1 mAbs (triangle). Data shown (mean±SEM) are from 2 pooled independent experiments each with 2-3 mice per group ",
    "ncbi_link": "Myd88: 17874"
  },
  {
    "caption": "CD86 MFI and percentages of cytokine-producing cells within pDC of each indicated mouse strain. Black, C57BL6; red, Ifnar1-/-; orange, Ifnar1-/-x Myd88-/-",
    "ncbi_link": "Ifnar1: 15975
Myd88: 17874"
  },
  {
    "caption": "CD86 MFI and percentages of cytokine-producing cells within pDC of each indicated mouse strain. Black, C57BL6 green, Tlr9-/- and pale green, Tlr7-/-. In (K-L) indicated mice were treated with IC (square) or blocking α-IFNAR1 mAbs (triangle). Data depicted (mean±SEM) are from 2 pooled independent experiments each with 2-3 mice per group.",
    "ncbi_link": "Tlr7: 170743
Tlr9: 81897"
  },
  {
    "caption": " (A) IRF7 protein expression in pDC isolated from Irf7-/- (pink, bottom), C57BL/6 (WT, black, top) and Ifnar1-/- (red, middle) uninfected (empty histograms, Ø, left) vs MCMV-infected mice (filled histograms, MCMV, right). For each condition histograms are representative of one out of 4-6 mice from 2 independent experiments ",
    "ncbi_link": "Ifnar1: 15975
Irf7: 54123"
  },
  {
    "caption": " (B) IRF7 protein expression in pDC (left), cDC (middle) and conventional monocytes (cMo, right) isolated from uninfected (Ø, empty) or MCMV-infected (MCMV, filled) C57BL/6 (black) or Ifnar1-/- (red) mice. Data are shown as net IRF7 MFI, after subtraction of the MFI obtained using isotype control mAbs. Data shown (mean±SEM) are pooled from 2 independent experiments with 5-6 mice for each group ",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": " (C-E) The expression of CD86 (C) or of indicated cytokines (D-E) was analyzed, as described in Fig 2. Black, CTR MBMC; pink, Irf7-TST MBMC. Mice were treated with isotype control (IC, square) or blocking α-IFNAR1 mAbs (triangle). Data shown (mean±SEM) are from 2 pooled independent experiments each with 2-3 mice per group",
    "ncbi_link": "Irf7: 54123"
  },
  {
    "caption": "Ratio of CD86 expression or IFN-I production in 5.2+ vs 5.1+ pDC isolated from MCMV-infected MBMC of each indicated type. Black, CTR MBMC; pale pink, Itgal-TST MBMC. Data shown (mean±SEM) are from 2 pooled independent experiments each with 3 mice per group.",
    "ncbi_link": "Itgal: 16408"
  },
  {
    "caption": "Ratio of CD86 expression or IFN-I production in 5.2+ vs 5.1+ pDC isolated from CpG-stimulated (B) MBMC of each indicated type. Black, CTR MBMC; pale pink, Itgal-TST MBMC. Data shown (mean±SEM) are from 2 pooled independent experiments each with 3 mice per group.",
    "ncbi_link": "Itgal: 16408"
  },
  {
    "caption": "(C) EYFP expression in splenocytes isolated from uninfected (NI) vs MCMV-infected (MCMV) IFNbtm1(EYFP) reporter mice. The expression of indicated markers was analyzed on YFP+ cells. Plots are representative of one out of 6 mice from 2 independent experiments.",
    "ncbi_link": "EYFP: 
IFNb: 15977"
  },
  {
    "caption": "(A) Localization of Ape1 relative to Ykt6 and Sec63 during nitrogen starvation. Cells expressing GFP-tagged Ykt6 under the control of the GAL1 promoter and tdTomato-tagged Sec63 were transformed with a centromeric plasmid expressing BFP-Ape1. Cells were grown in SGC-LEU, shifted to SG-N for the indicated time, and analyzed by fluorescence microscopy. Images are shown as single planes. Scale bar, 5 µm. Arrows indicate Ykt6 dots colocalizing with Ape1. (B) Percentage of Ykt6 puncta simultaneously co-localizing with both Ape1 and Sec63. The data were quantified from (A). Error bars represent standard deviation of three independent experiments. Cells (n≥250) and Ape1 dots (n≥50) were quantified.",
    "ncbi_link": "GAL1: 852308"
  },
  {
    "caption": "(C) Localization of Ykt6 relative to different organelle marker proteins during nitrogen starvation. Cells expressing GFP-tagged Ykt6 under the control of the GAL1 promoter and tdTomato-tagged Snx41 (endosomes), Sec63 (ER), Vac8 (vacuole), or Mnn9 (Golgi) were were grown in SGC-LEU, then shifted to SG-N for 2 h, and analyzed by fluorescence microscopy. Single imaging planes are shown. Scale bar, 5 µm. Arrows indicate Ykt6 dots that colocalize with marker proteins.",
    "ncbi_link": "GAL1: 852308"
  },
  {
    "caption": "Localization of Ykt6 in multiple atg mutants. (A) Wild-type or the respective mutant cells expressing mCherry-tagged Ape1 and GFP-tagged Ykt6 were grown in SGC to allow for Ykt6 expression from the GAL1-promoter and analyzed Arrows in the images indicate dots of Ykt6 colocalizing with Ape1 (A)",
    "ncbi_link": "GAL1: 852308"
  },
  {
    "caption": "(A) Effect of ykt6 and dsl1 complex ts mutants on autophagosome-vacuole fusion. Cells carrying a CEN plasmid expressing GFP-Atg8 were grown at 24°C in SGC and then shifted to SG-N for 2 h at 24°C or 37°C. Vacuoles were stained by FM4-64 and analyzed by fluorescence microscopy. Scale bar, 5 µm. Scale bar of inset is 0.6 µm.",
    "ncbi_link": "ykt6: 853638"
  },
  {
    "caption": "(C) Protease protection assay of ykt6-11 and dsl3 mutants. Lysates of atg1∆, ypt7∆, ykt6ts and dsl3ts cells carrying a CEN plasmid expressing GFP-Atg8 were grown at 37°C and subjected to the protease (PK)-protection",
    "ncbi_link": "atg1: 852695
dsl3: 851161
ykt6: 853638
ypt7: 855012"
  },
  {
    "caption": "(D) Localization of Atg8 relative to Atg1 during nitrogen starvation condition in sec12-1 ts mutant. Cells carrying a CEN plasmid expressing GFP-Atg8 and encoding 3xmCherry-tagged Atg1 were grown at 24°C in SDC and then shifted to SD-N for 2 h at 24°C or 37°C, and analyzed by fluorescence microscopy. Individual slices are shown. Scale bar, 5 µm. Scale bar of inset is 0.6 µm. Arrows in images indicate dots colocalization of Atg1 with Atg8 (D)",
    "ncbi_link": "sec12: 855760"
  },
  {
    "caption": "(E) Localization of Ykt6 relative to Dsl1 during growth and nitrogen starvation conditions. Cells expressing GFP-tagged Ykt6 under the control of the PHO5 promoter and genomically 3xmCherry-tagged Dsl1 were grown in SDC or SD-N for 2 h, and analyzed by fluorescence microscopy. Individual slices are shown. Scale bar, 5 µm. (F) Percentage of Ykt6 puncta co-localizing with Dsl1. The data was quantified from (E). Error bars represent standard deviation of three independent experiments. Cells (n≥250) and Dsl1 dots (n≥50) were quantified. Arrows in images indicate dots colocalization of Ykt6 with Dsl1 (E).",
    "ncbi_link": "PHO5: 852390"
  },
  {
    "caption": "(A) Effect of Dsl and COPII ts mutants on Ykt6 localization to autophagosomes. Wild-type and selected ts strains (sec12-1, tip20-5 and dsl3-2) expressing GFP-tagged Ykt6 and mCherry-tagged Atg8 were grown at 24°C in SGC for 8 h and then shifted to SG-N for 2 h at 37°C. Vacuoles were stained by CMAC and analyzed by fluorescence microscopy. Scale bar, 5 µm. Scale bar in inset, 0.7 µm. Arrows indicate dot colocalization of Ykt6 and Atg8 (A)",
    "ncbi_link": "sec12: 855760
dsl3: 851161
tip20: 852732"
  },
  {
    "caption": "Wild-type and selected ts strains (sec12-1, tip20-5 and dsl3-2) expressing GFP-tagged Ykt6 and mCherry-tagged Atg8 were grown at 24°C in SGC for 8 h and then shifted to SG-N for 2 h at 37°C. (B) Percentage of Ykt6 puncta co-localizing with Atg8. Cells (n≥150) and Atg8 dots (n≥100) were quantified.",
    "ncbi_link": "sec12: 855760
dsl3: 851161
tip20: 852732"
  },
  {
    "caption": "(C) Localization of Ykt6 relative to Sec63 and Sec13 during growth and nitrogen starvation conditions. tip20-5 cells expressing GFP-tagged Ykt6 and 3xmCherry-tagged Sec63 or Sec13 were grown at 24°C in SGC for 8 h and then shifted to SG-N for 2 h at 24°C or 37°C, and analyzed by fluorescence microscopy. Scale bar, 5 µm. Scale bar of inset, 0.7 µm. Arrows indicate dot colocalization of Ykt6 with Sec63 (C).",
    "ncbi_link": "tip20: 852732"
  },
  {
    "caption": "(D) Effect of dsl mutation on autophagosome-vacuole fusion in vitro. The vam3∆ or dsl ts strain expressing Atg9-3xFLAG and GFP-Atg8 were starved for 3 h at 30°C before purifying autophagosomes, which was sufficient to induce the ts phenotype. Vacuoles were isolated from pep4∆ cells expressing Vac8-3xmCherry and then incubated with autophagosomes at 26°C for 1 h with or without ATP (E) Quantification of (D). Error bars represent standard deviation of 3 independent experiments. Fluorescence intensity of GFP-Atg8 in the vacuolar lumen was quantified by image J using the ROI (region of interest) manager tool. Vacuoles (n≥40) for each experiment were quantified.",
    "ncbi_link": "pep4: 855949
vam3: 854273"
  },
  {
    "caption": "(A-B) Quantification of size and number of autophagosomes in the indicated ts mutant strains. Error bars represent standard deviation of 3 independent experiments. GFP-tagged Atg8 in the different mutants were grown at 23°C (ts mutant) or 30°C (atg1∆) in SDC and then shifted to SD-N for 2 h at 30°C (atg1∆) or 37°C (ts mutant), and analyzed by fluorescence microscopy. Scale bar, 1 µm.",
    "ncbi_link": "atg1: 852695"
  },
  {
    "caption": "(C) Localization of Atg8 relative to Atg9 during nitrogen starvation. dsl3 cells expressing mCherry-tagged Atg9 and carrying a CEN plasmid expressing GFP-Atg8 were grown at 23°C in SDC and then shifted to SD-N for 2 h at 24°C or 37°C. Cells were analyzed by fluorescence microscopy. Scale bar, 5 µm. Scale bar for inset is 0.6 µm.",
    "ncbi_link": "dsl3: 851161"
  },
  {
    "caption": "(D) Atg9 localization in dsl3 cells during starvation. dsl3 ts cells expressing mCherry-tagged Atg9, and carrying a CEN plasmid expressing GFP-Atg8 and plasmid pRS315-CUP1pr-BFP-APE1 were grown in SDC medium containing CuSO4 to induce formation of the giant Ape1 structure, and starved for 1 h. Cells were analyzed by fluorescence microscopy. Scale bar, 5 µm. Scale bar for inset is 0.6 µm.",
    "ncbi_link": "dsl3: 851161"
  },
  {
    "caption": "(B) Localization of Ykt6 relative to Atg1 during growth and nitrogen starvation conditions. Cells expressing GFP-tagged Ykt6 under the control of the PHO5 promoter and genomically 3xmCherry-tagged Atg1 were grown in SDC or SD-N for 2 h, and analyzed by fluorescence microscopy. Individual slices are shown. Scale bar, 5 µm. Scale bar of inset is 0.6 µm. Right, percentage of Ykt6 puncta co-localizing with Atg1. Error bars represent standard deviation of three independent experiments. Cells (n≥200) and Atg1 dots (n≥100) were quantified. Arrows indicate Ykt6 positive dots colocalizing with Atg1 (B)",
    "ncbi_link": "PHO5: 852390"
  },
  {
    "caption": "(D) Localization of Ykt6 relative to Atg8 under growth and nitrogen starvation conditions. Wild-type and atg1D211A cells expressing GFP-tagged Ykt6 under the control of the PHO5 promoter and genomically Cherry-tagged Atg8 were grown in SDC or SD-N for 2 h, and analyzed by fluorescence microscopy. Individual focal planes are shown. Scale bar, 5 µm. (E) Percentage of Ykt6 puncta co-localizing with Atg8. Numbers in the column indicates the percentage. Cells (n≥300) and Atg8 dots (n≥60) were quantified. Arrows indicate Ykt6 positive dots colocalizing with Atg8 (D).",
    "ncbi_link": "atg1: 852695
PHO5: 852390"
  },
  {
    "caption": "(A) Growth test of Ykt6 wild-type and mutants. ykt6∆ cells carrying a URA3 plasmid coding for wild-type Ykt6 and pRS413-GAL1pr-YKT6-GFP (wild-type or mutant) were spotted as serial dilutions on SGC-HIS to select for the mutant plasmid or 5-Fluoroorotic acid (5-FOA) to force the loss of the plasmid coding for wild-type Ykt6.",
    "ncbi_link": "GAL1: 852308
Ykt6: 853638
ykt6: 853638"
  },
  {
    "caption": "(B) Effect of Ykt6 phospho-mutants on autophagy. ykt6∆ cells expressing wild-type Ykt6 plus a pRS413 plasmid encoding GAL1pr-YKT6 (wild-type or mutants with S to A mutations [SA; S182, S183A], or S to D mutations [SD; S182D, S183D]), and a plasmid expressing GFP-Atg8 were grown in SGC and then shifted to SG-N for 2 h. Cells were analyzed by fluorescence microscopy. Individual slices are shown. Scale bar, 5 µm. (C) Quantification of Atg8 dots per cell from images in (B). Cells (n≥100) and Atg8 dots (n≥50) were quantified.",
    "ncbi_link": "ykt6: 853638
Ykt6: 853638
YKT6: 853638"
  },
  {
    "caption": "(D) Effect of Atg1-Atg13 subcomplex on autophagosome-vacuole fusion in vitro. The vam3∆ strain carrying pRS413 plasmid encoding GAL1pr-YKT6 (wild-type or mutant), and expressing Atg9-3xFLAG and GFP-Atg8, were starved for 3 h at 30°C before purifying autophagosomes. Vacuoles were isolated from pep4∆ cells expressing Vac8-3xmCherry and then incubated with autophagosomes in the presence or absence of 50 nM Atg1-Atg13 subcomplex at 26°C for 1 h with or without ATP (E) Quantification of (D). Error bars represent standard deviation of 3 independent experiments. Fluorescence intensity of GFP-Atg8 in the vacuolar lumen was quantified by image J using the ROI (region of interest) manager tool. Vacuoles (n≥40) for each experiment were quantified.",
    "ncbi_link": "pep4: 855949
vam3: 854273
YKT6: 853638"
  },
  {
    "caption": "(A,B) PTPRN2 (A) and PLCB1 (B) expression levels were determined by qRT-PCR.",
    "ncbi_link": "PLCB1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(C) Bioluminescence imaging quantification of lung colonization by 40,000 LM2 breast cancer cells transduced with shRNAs targeting PTPRN2 or a control hairpin. For shCntrl, sh1PTPRN2, N = 5 mice/group. For sh2PTPRN2 N = 6 mice. Right, H&E staining of representative lung sections.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(D) Bioluminescence imaging quantification of lung colonization by 40,000 LM2 cells transfected with siRNA targeting PLCβ1 or a control siRNA. For siCntrl, N = 5 mice. For si1PLCβ1, si2PLCβ1, N = 6 mice/group. Right, H&E staining of representative lung sections.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(E,F) PTPRN2 (E) and PLCB1 (F) levels were analyzed in human breast cancers (stages I-IV) and normal breast tissue from TissueScan qPCR Array Breast Cancer Panels II and III (Origene, N = 97). Expression levels were normalized to levels in normal tissue for each gene.",
    "ncbi_link": "PLCB1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(G) Kaplan-Meier curve representing overall survival of a cohort of breast cancer patients (N = 528) as a function of their primary tumor's PTPRN2 and PLCB1 expression levels (data from the TCGA Research Network (Cancer Genome Atlas, 2012)). Patients whose primary tumors' PTPRN2 and PLCB1 expression levels were higher or lower than the median of the population were classified as low (blue) or high (red) expression.",
    "ncbi_link": "PLCB1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(H) Kaplan-Meier curve representing distal metastasis-free survival of a cohort of breast cancer patients (N = 1609) as a function of their primary tumor's PTPRN2 and PLCB1 expression levels (Data from KMPlot (Gyorffy et al., 2010)). Patients' primary tumors' PTPRN2 and PLCB1 expression levels were classified as low (blue) or high (red) expression.",
    "ncbi_link": "PLCB1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(A) Matrigel invasion by 50,000 LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or control siRNA. Data normalized to control values. N = 6 inserts/group.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(B) Migration assay by 100,000 LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or control siRNA. Data normalized to control values. N = 6 inserts/group. Right, representative images of the migration assay. Scale bar, 100 μm.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(C) Quantification of area covered by cells 24 h after a scratch was made through confluent cells transfected with siRNA targeting PTPRN2, PLCβ1, or control siRNA. N = 5 wells/group. Right, representative images of the scratch assay.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(D,E) MDA-MB-231 cells transduced with PTPRN2, PTPRN2C945A, or control vector were subjected to the Matrigel invasion (D) and migration assays (E). N = 5 inserts/group.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(F) Bioluminescence imaging quantification of lung colonization by 40,000 MDA-MB-231 cells overexpressing PTPRN2, PTPRN2C945A, or control vector. N = 5 mice/group. Right, H&E staining of representative lung sections.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(G,H) MDA-MB-231 cells transduced with PLCβ1, PLCβ1H331Q, or control vector were subjected to the Matrigel invasion (G) and migration assays (H). N = 5 inserts/group.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(I) Bioluminescence imaging quantification of lung colonization by 40,000 MDA-MB-231 cells overexpressing PLCβ1, PLCβ1H331Q, or control vector. For Cntrl and PLCβ1H331Q OE, N = 6 mice/group. For PLCβ1 OE, N = 5 mice. Right, H&E staining of representative lung sections.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(C,D) MDA-MB-231 cells overexpressing PTPRN2, PLCβ1, or a control vector (C) or LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or a control siRNA (D) were immunostained for PI(4,5)P2 levels and analyzed by fluorescence microscopy. Mean fluorescence intensity of plasma membrane levels of the lipid were quantified. N = 50 cells/group. Left, representative immunofluorescence images of cells stained with anti-PI(4,5)P2 antibody (red) and 4',6-diamidino-2-phenylindole (DAPI, blue). Scale bar, 10 μm.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(A,B) LM2 cells transfected with siRNA targeting PTPRN2 (A), PLCβ1 (B) or a control siRNA were transfected with Lyn11-FRB and INPP5E-FKBP, treated with either DMSO or 100 nm rapamycin and subjected to the migration assay. N = 5 inserts/group.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(C,D) MDA-MB-231 cells overexpressing PTPRN2 (C), PLCβ1 (D) or control vector were treated with carrier alone or carrier incubated with PI(4,5)P2 for one hour and then immediately subjected to the migration assay. N = 5 inserts/group.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(C,D) MDA-MB-231 cells overexpressing PTPRN2 (C), PLCβ1 (D) or control vector were treated with carrier alone or carrier incubated with PI(4,5)P2 for one hour and then immediately subjected to the migration assay. N = 5 inserts/group.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(E) Kaplan-Meier curve representing distal metastasis-free survival of a cohort of breast cancer patients (N = 1609) as a function of their primary tumor's mean PIP5K1A, PIP5KB, and PIP5KC expression levels (Data from KMPlot (Gyorffy et al., 2010)). Patients' primary tumors' combined PIP5K expression levels were classified as low (blue) or high (red) expression.",
    "ncbi_link": "PIP5K1A: 8394
PIP5KB: 8395
PIP5KC: 23396"
  },
  {
    "caption": "(F,G) Migration (F) and Matrigel invasion (G) of LM2 cells transduced with a retroviral vector overexpressing PIP5K1A or control vector. Data normalized to control values. N = 5 inserts/group.",
    "ncbi_link": "PIP5K1A: 8394"
  },
  {
    "caption": "(A) Kaplan-Meier curve representing distal metastasis-free survival of a cohort of breast cancer patients (N = 1609) as a function of their primary tumor's CFL1 expression levels (Data from KMPlot (Gyorffy et al., 2010)). Patients' primary tumors' CFL1 expression levels were classified as low (blue) or high (red) expression.",
    "ncbi_link": "CFL1: 1072"
  },
  {
    "caption": "(B,C) Membrane and membrane-associated proteins were purified from cells transfected with siRNA targeting PTPRN2 (B) or PLCβ1 (C) or control siRNA. Fractions were subjected to Western blot analysis for CFL1 and EGFR levels. Right, densitometry analysis of CFL1 levels normalized to EGFR levels.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(B,C) Membrane and membrane-associated proteins were purified from cells transfected with siRNA targeting PTPRN2 (B) or PLCβ1 (C) or control siRNA. Fractions were subjected to Western blot analysis for CFL1 and EGFR levels. Right, densitometry analysis of CFL1 levels normalized to EGFR levels.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(D,E) Membrane and membrane-associated proteins were purified from cells overexpressing PTPRN2 (D), PLCβ1 (E) or a control vector. Fractions were subjected to Western blot analysis for CFL1 and EGFR levels. Right, densitometry analysis of CFL1 levels normalized to EGFR levels.",
    "ncbi_link": "PTPRN2: 5799"
  },
  {
    "caption": "(D,E) Membrane and membrane-associated proteins were purified from cells overexpressing PTPRN2 (D), PLCβ1 (E) or a control vector. Fractions were subjected to Western blot analysis for CFL1 and EGFR levels. Right, densitometry analysis of CFL1 levels normalized to EGFR levels.",
    "ncbi_link": "PLCβ1: 23236"
  },
  {
    "caption": "(F) LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or control siRNA were partially permeabilized and incubated with biotin-actin monomers. Cells were stained for incorporated biotin-actin monomers using Streptavidin-555 (red) and DAPI (blue). Right, quantification of mean fluorescence intensity of incorporated biotin-actin monomers. N = 100 cells/group. Scale bar, 20 μm.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(A) LM2 cells transfected with siRNA targeting PTPRN2, PLCβ1, or control siRNA were stained with phalloidin (red) and DAPI (blue) and analyzed using fluorescence microscopy. Right, mean fluorescence intensity quantification of whole cell phalloidin signal. N = 40 cells/group. Scale bar, 10 μm.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(B) Mean fluorescence intensity quantification of whole cell phalloidin signal in MDA-MB-231 cells overexpressing PTPRN2, PLCβ1, or control vector. N = 40 cells/group.",
    "ncbi_link": "PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "(C,D) MDA-MB-231 cells were transfected with siRNAs targeting CFL1 or a control siRNA in the setting of control or PTPRN2 overexpression and subjected to the migration (C) or invasion (D) assays. N = 5 inserts/group.",
    "ncbi_link": "CFL1: 1072
PTPRN2: 5799"
  },
  {
    "caption": "(E) MDA-MB-231 cells were transfected with siRNAs targeting CFL1 or a control siRNA in the setting of control or PLCβ1 overexpression were subjected to the migration assay. N = 5 inserts/group.",
    "ncbi_link": "CFL1: 1072
PLCβ1: 23236"
  },
  {
    "caption": "(F) Bioluminescence imaging quantification of 40,000 MDA-MB-231 cells overexpressing PTPRN2 or control vector and transfected with control siRNA or siRNA targeting CFL1. Right, H&E staining of representative lung sections. N = 5 mice/group.",
    "ncbi_link": "CFL1: 1072
PTPRN2: 5799"
  },
  {
    "caption": "(G,H) MDA-MB-231 cells overexpressing PTPRN2 (G) or PLCβ1 (H) were transfected with siRNA targeting the 3'UTR of CFL1 to deplete endogenous CFL1. Cells were further transfected with plasmids encoding either GFP-CFL1-WT or GFP-CFL1-Lck and subjected to the migration assay. N = 5 inserts/group.",
    "ncbi_link": "CFL1: 1072
PLCβ1: 23236
PTPRN2: 5799"
  },
  {
    "caption": "C Subcellular fractionation of the WT and NLS-deficient FolSrpk1-GFP  proteins. N, nucleus; C, cytosol. The amount of nuclear FolSrpk1-GFP  was set as 1. Data information: For C, each gel shown is a representative experiment carried out at least three times. The fractionation controls were Fol histone H1 (nucleus), Actin  (cytosol) and Coomassie brilliant blue (CBB) staining.",
    "ncbi_link": "GFP: 
Srpk1: 28948139"
  },
  {
    "caption": "D Quantitative measurement of H2O2  in tomato roots  after infection by the WT and FolSrpk1p::FolSrpk1-GFP  strains at 0-5 days post incubation (dpi). Data are presented as mean ± SD. The presence of different letters above the mean values of three replicates indicates a significant difference between different samples (P < 0.05, ANOVA).",
    "ncbi_link": "GFP: 
Srpk1: 28948139"
  },
  {
    "caption": "G Fluorescence microscopy analysis of FolSrpk1-GFP  in mycelia   of the FolSrpk1p::FolSrpk1-GFP  strain treated with 10 mM H2O2  for 0, 1 and 2 h. Arrows indicate the nucleus. Scale bars = 5 µm.",
    "ncbi_link": "GFP: 
Srpk1: 28948139"
  },
  {
    "caption": "I Subcellular fractionation analysis of  FolSrpk1-GFP  in mycelia  of the  FolSrpk1p::FolSrpk1-GFP  strain treated with 10 mM H2O2  for 0, 1 and 2 h. The amount of nuclear FolSrpk1-GFP  at 0 h was set as 1. Data information: For I, each gel shown is a representative experiment carried out at least three times. The fractionation controls were Fol histone H1 (nucleus), Actin  (cytosol) and Coomassie brilliant blue (CBB) staining.",
    "ncbi_link": "GFP: 
Srpk1: 28948139"
  },
  {
    "caption": "H Subcellular fractionation of FolSrpk1-GFP  and its mutant forms. The fractionation controls were Fol histone H1 (nucleus), Actin  (cytosol) and CBB staining. The amount of nuclear FolSrpk1-GFP  was set as 1. Data information: For H, , each gel shown is a representative experiment carried out at least three times.",
    "ncbi_link": "GFP: 
Srpk1: 28948139"
  },
  {
    "caption": "A K304 acetylation  (top) and amount (middle) of FolSrpk1-GFP  and FolSrpk1K304Q-GFP  in WT and FolArd1-OE strains treated with 10 mM H2O2  for 2 h. The over-expressed FolArd1-Flag  was detected by anti-Flag  (bottom). The amount of acetylated  and total FolSrpk1 in the WT was each set as 1. Data information: each gel shown is a representative experiment carried out three times.",
    "ncbi_link": "Ard1: 28947107"
  },
  {
    "caption": "E Subcellular fractionation analysis of FolSrpk1-GFP  in WT, ΔFolSir2, and FolSir2-OE strains. The amount of nuclear FolSrpk1-GFP  in the WT was set as 1. Data information: each gel shown is a representative experiment carried out three times. The fractionation controls were Fol histone H1 (nucleus), Actin  (cytosol) and CBB staining.",
    "ncbi_link": "Sir2: 28948117"
  },
  {
    "caption": "G, H Expression  profile of  FolArd1 (G) and FolSir2  (H) during the infection stage. Total RNA extracted from host roots  at 0 (conidia) and 1-5 dpi was reverse transcribed. The expression  levels were normalized to that of the Fol actin  gene. Data are presented as mean ± SD. The presence of different letters above the mean values of three replicates indicates a significant difference between different samples (P < 0.05, ANOVA).",
    "ncbi_link": "actin: 28942483
Ard1: 28947107
Sir2: 28948117"
  },
  {
    "caption": "B Secretion of the  FOXG_17180-GFP, FOXG_15294-GFP  and FOXG_13788-GFP  proteins. The proteins extracted from mycelia  (M) and culture supernatants  (S) were analyzed by  Western blotting with anti-GFP  and anti-Actin. Each gel shown is a representative experiment carried out three times. The loading controls were Fol Actin  and  CBB staining.",
    "ncbi_link": "GFP: 
FOXG_13788: 28955025
FOXG_15294: 28956366
FOXG_17180: 28957973"
  },
  {
    "caption": "F qRT-PCR analysis of Fol EF-1α transcript levels in tomato roots  14 days after infection by the indicated strains. The expression of tomato RCE1  was used as a control to ensure the use of equal amounts of RNA for  RT-PCR. Data information: For F, the presence of different letters above the mean values of four replicates indicates a significant difference between different samples (P < 0.05, ANOVA). The whiskers of the boxplots indicate the upper and lower quartiles, the boxes indicate the interquartile range, and the plus sign indicates the mean.",
    "ncbi_link": "RCE1: 
EF-1α: 28945635"
  },
  {
    "caption": "F qRT-PCR analysis of Fol EF-1α transcript levels in tomato roots  14 days after infection by the indicated strains. The experiments (four biological replicates) Data information: For F, the presence of different letters above the mean values of four replicates indicates a significant difference between different samples (P < 0.05, ANOVA). The whiskers of the boxplots indicate the upper and lower quartiles, the boxes indicate the interquartile range, and the plus sign indicates the mean.",
    "ncbi_link": "EF-1α: 28945635"
  },
  {
    "caption": "A Subcellular fractionation of BcSrpk1-GFP  in WT and BcSrpk1mutant strains. The amount of nuclear BcSrpk1-GFP  was set as 1. Data information: , each gel shown is a representative experiment carried out three times. The fractionation controls were histone H1 (nucleus), Actin  (cytosol) and CBB staining.",
    "ncbi_link": "GFP: 
Srpk1: "
  },
  {
    "caption": "C. BiFC assay to verify the interaction between FREE1 and CPL1. YC-FREE1 and YN-CPL1, were co-expressed with mCherry-HYL1, SE-mCherry, or DCL1-mCherry in Arabidopsis protoplasts, respectively, followed by confocal observation.",
    "ncbi_link": "mCherry: 
DCL1: 839574
HYL1: 837498
SE: 817252"
  },
  {
    "caption": "D. Co-immunoprecipitation analysis of interactions between FREE1 and CPL1 and CPL2. Arabidopsis protoplasts co-expressing mCherry-FREE1 with YFP, YFP-CPL1 or YFP-CPL2 were subjected to protein extraction and IP with GFP-trap followed by immunoblotting with mCherry and GFP antibodies.",
    "ncbi_link": "mCherry: 
YFP: 
FREE1: 838600
CPL1: 828254
CPL2: 831743"
  },
  {
    "caption": "E. Co-immunoprecipitation analysis of the associations between FREE1 and microprocessor components. Transgenic plants expressing GFP-FREE1 were subjected to protein extraction and IP with GFP-trap followed by immunoblotting with indicated antibodies.",
    "ncbi_link": "GFP: 
FREE1: 838600"
  },
  {
    "caption": "B. Small RNA gel blots for 7-day-old seedlings Col-0 and free1-ctmut plants. U6 was used as a loading control. The numbers indicate the relative abundance of miR168, miR166, miR162, siRNA1003, tasiRNA255, IR71, miR156 and miR172 in the plants (the intensity in WT was arbitrarily annotated as 1.00).",
    "ncbi_link": "IR71: 
siRNA1003: 
tasiRNA255: 
free1: 838600
miR156: 28721198///3770614///28721147///28720200///28720191///28718303
miR162: 28721190///28720955
miR166: 3771553///3771422///3771398///3770612///3770611///3769765///28718357
miR168: 28721252///28720148
miR172: 5008315///5008089///5007991///3770659///28718310
U6: 28719273"
  },
  {
    "caption": "A. Detection of HYL1 phosphorylation in Col-0, free1-ctmut or cpl1-8. Proteins extracted from 7-day-old Arabidopsis seedlings were separated by Phos-tag polyacrylamide gels or SDS polyacrylamide gels followed by immunoblotting with indicated antibodies. The numbers in the first row indicate the relative grayscale intensities of total HYL1, the numbers in the second row indicate the relative intensities of dephosphorylated HYL1 and phosphorylated HYL1, and the intensity in WT was arbitrarily set to 1.00.",
    "ncbi_link": "free1: 838600
cpl1: 828254"
  },
  {
    "caption": "B. Transgenic plants expressing pHYL1:: YFP-HYL1 in Col-0, free1-ctmut or cpl1-8 backgrounds were subjected to protein extraction and IP with GFP-trap, followed by detection with phos-tag BTL-111 or GFP antibody. The numbers indicate the relative intensities of each band detected with phos-tag BTL-111 and anti-GFP, and the first lane was arbitrarily set to 1.00.",
    "ncbi_link": "YFP: 
free1: 838600
cpl1: 828254
HYL1: 837498"
  },
  {
    "caption": "C. Confocal observation of the YFP-HYL1-containing D-bodies in Col-0 and free1-ctmut roots. Arrows indicated the YFP-HYL1-containing D-bodies. D. Statistically analysis of the number of YFP-HYL1-containing D-bodies as shown in Fig 4C. The X-axis represents the number of D-bodies per cell, and the Y-axis represents the percentage of cells with the corresponding numbers. The quantification was performed by observing more than 400 cells from 20 roots for each genotype",
    "ncbi_link": "free1: 838600"
  },
  {
    "caption": "E. Protein abundance of core components of miRNA processing complex in Col-0 and free1-ctmut. Proteins extracted from 7-day-old Arabidopsis seedlings were used for immunoblotting with indicated antibodies. The numbers represent the intensities of each band detected with indicated antibody relative to anti-UGPase, and the first lane was arbitrarily set to 1.00.",
    "ncbi_link": "free1: 838600"
  },
  {
    "caption": "A. Proteins extracted from Arabidopsis protoplasts co-expressing YFP-CPL1 and different amount of 3myc-FREE1 were used for immunoprecipitation with GFP-Trap followed by detection with indicated antibodies.",
    "ncbi_link": "3myc: 
YFP: 
FREE1: 838600
CPL1: 828254"
  },
  {
    "caption": "B. Proteins extracted from transgenic plants expressing YFP-CPL1 in Col-0 or free1-ctmut background were used for IP with GFP-trap followed by immunoblotting analysis with indicated antibodies.",
    "ncbi_link": "YFP: 
free1: 838600
CPL1: 828254"
  },
  {
    "caption": "C. Statistically analysis of the relative intensity of FREE1, HYL1 and SE in Col-0 or free1-ctmut background (IP/Input). Data are presented as means ± s.d. (3 biological replicates), the asterisk indicates significant difference between the samples (**P < 0.01 by Student's t-test, compared with WT).",
    "ncbi_link": "free1: 838600"
  },
  {
    "caption": "D. Transgenic plants of YFP-HYL1 / WT, YFP-HYL1 / free1-ctmut, YFP-HYL1 / cpl1-8 and GFP / WT were subjected to protein extraction and IP with GFP-trap followed by immunoblotting analysis with indicated antibodies.",
    "ncbi_link": "YFP: 
free1: 838600
cpl1: 828254
HYL1: 837498"
  },
  {
    "caption": "Sample recordings from 7-week-old  hESC-derived Cerebral Organoids (COs). Sample traces show visible differences in local field potential, with WWOX-KO  COs (Red) showing increased activity compared to WT (Blue) in baseline condition (Left) and in the presence of 100µM 4AP (Right).",
    "ncbi_link": "WWOX: 51741"
  },
  {
    "caption": "Sample recordings from 7-week-old hESC-derived  Cerebral Organoids (COs). WWOX's coding sequence was re-introduced into week 6 WWOX-KO  COs using lentiviral transduction (lenti-WWOX) (F) Immunofluorescent staining  showing WWOX expression in different populations in WWOX-KO  organoids following infection with  lentivirus. NT= non-treated. Scale = 50µm .",
    "ncbi_link": "WWOX: 51741"
  },
  {
    "caption": "(A) Fluorescence profiles of mNG-PilG  in chpA  mutants after 2h on surfaces. Solid lines, mean normalized fluorescence profiles across biological replicates. Shaded area, standard deviation across biological replicates.",
    "ncbi_link": "chpA: 878176"
  },
  {
    "caption": "(D) Polar localization  profiles of mNG-PilG  in ΔfimL  and ΔfimL  ΔchpA mutant after 2h on surfaces.",
    "ncbi_link": "chpA: 878176
fimL: 881776"
  },
  {
    "caption": "(A) mNG-PilH  fluorescence profiles in chpA  mutants after 2h surface growth. To avoid negative effects of low cAMP  level on localization  of PilH, cpdA  was deleted in all displayed strains to rescue cAMP  level to WT levels Solid lines, mean normalized fluorescence profiles across biological replicates. Shaded area, standard deviation across biological replicates.",
    "ncbi_link": "chpA: 878176
cpdA: 880028"
  },
  {
    "caption": "C) Fluorescence profiles of mNG-PilHGOF after 2h on surface in chpA  mutants. C) Solid lines, mean normalized fluorescence profiles across biological replicates. Shaded area, standard deviation across biological replicates.",
    "ncbi_link": "chpA: 878176"
  },
  {
    "caption": "(A) mNG-PilH  fluorescence profiles in ΔpilG after 2h surface growth (low cAMP).",
    "ncbi_link": "pilG: 878203"
  },
  {
    "caption": "(C) mNG-PilH  fluorescence profiles in ΔpilG ΔcpdA  after 2h surface growth (rescued cAMP).",
    "ncbi_link": "cpdA: 880028
pilG: 878203"
  },
  {
    "caption": "(A) mNG-PilG  fluorescence profiles in pilH  mutants after 2h surface growth. We included ΔcpdA for comparison since both pilH  mutations result in high cAMP  levels. PilG  is more polar and asymmetric in ΔpilH  and pilHLOF. (A Solid lines, mean normalized fluorescence profiles across biological replicates. Shaded area, standard deviation across biological replicates.",
    "ncbi_link": "cpdA: 880028
pilH: 878198"
  },
  {
    "caption": "(D) Time course of PilG localization  in pilHGOF on surface. For clarity only the 2h profile of PilG  in wild type was included. D) Solid lines, mean normalized fluorescence profiles across biological replicates. Shaded area, standard deviation across biological replicates.",
    "ncbi_link": "pilH: 878198"
  },
  {
    "caption": "(A, Time course  fluorescence profiles and polar localization  indexes of mNG-PilG  in ΔpilA. PilG  polar localization  index remains unchanged on surfaces in ΔpilA  similar to surface-adapted WT",
    "ncbi_link": "pilA: 878423"
  },
  {
    "caption": "(C Time course fluorescence profiles and polar localization  indexes of mNG-PilH  in ΔpilA. Like in WT, PilH  gets recruited to the poles over time  in ΔpilA, although at a slower speed",
    "ncbi_link": "pilA: 878423"
  },
  {
    "caption": "B. T6SS secretion assay of A. tumefaciens strains: wild type C58, various mutants lacking one, two, or three toxin-immunity gene pairs, and a mutant lacking tssL.",
    "ncbi_link": "tssL: 1136207"
  },
  {
    "caption": "C. T6SS secretion assay of various A. tumefaciens strains: wild type C58, ΔtssL, the tde double deletion mutant (Δtdei) containing pRL662 and pTrc200 empty vector (V) only or expression of pTdei1 (tde1-tdi1 expressed from pTrc200), pTde2* (catalytic site mutated tde2 expressed on pRL662), or pTdei1+ pTde2*.",
    "ncbi_link": "Tde2: 1135514
tde2: 1135514
tde1: 1136224
tdi1: 1136225
tssL: 1136207"
  },
  {
    "caption": "A. T6SS secretion assay of A. tumefaciens strains: wild type C58, ΔtssL, Δtap-1, and Δatu3641 harboring a pTrc200 vector (V) or derivatives pTap-1 (tap-1 expressed from pTrc200), or p3641 (atu3641 expressed from pTrc200).",
    "ncbi_link": "atu3641: 1135515
tap-1: 1136223
Tap-1: 1136223
tssL: 1136207"
  },
  {
    "caption": "B. T6SS secretion assay of A. tumefaciens C58 Δtap-1Δatu3641 containing an empty pTrc200 vector (V) or its derivatives expressing tap-1, atu3641, tde1-tdi1, or tde2-tdi2.",
    "ncbi_link": "tdi2: 1135513
tde2: 1135514
atu3641: 1135515
tap-1: 1136223
tde1: 1136224
tdi1: 1136225"
  },
  {
    "caption": "A. Representative images of cells of A. tumefaciens C58 strains ΔtssB, ΔtssLΔtssB, and ΔtdeiΔtssB cells each expressing TssB-GFP from pTrc200. Upper panel: phase contrast images; Lower panel: green fluorescence images. Examples of GFP streaks were indicated by white arrowheads. Scale bar: 2 μm.",
    "ncbi_link": "tssB: 1136216
tssL: 1136207"
  },
  {
    "caption": "C. Western blots of the isolated sheaths, which were prepared via ultracentrifugation of cell lysates from A. tumefaciens C58 wild type, ΔtssL, and Δtdei. T: total proteins from the cell lysate. P: pellet samples containing TssBC sheaths after ultracentrifugation. S: supernatant after ultracentrifugation. Proteins were analyzed in western blots probed with indicated antibodies. Fha serves as a cytoplasmic control. Molecular weight markers (in kDa) are indicated on the left. Similar results were obtained from at least two independent experiments. Data are from one independent experiment and reproduced in at least two independent experiments.",
    "ncbi_link": "tssL: 1136207"
  },
  {
    "caption": "D. Secretion assay of wild type 12D1, ΔtssL, Δv1, Δv3-4 containing pRL662 empty vector (V) or its derivatives with v1 or v3-4 were analyzed for secretion.",
    "ncbi_link": "tssL: 
v1: 
v3: "
  },
  {
    "caption": "E. Secretion assay of wild type 1D1108, ΔtssL, Δv4, Δv6 containing pRL662 empty vector (V) or its derivatives with v4 or v6.",
    "ncbi_link": "v4: 
v6: 
tssL: 1136207"
  },
  {
    "caption": "A. T6SS secretion assay of A. tumefaciens wild type C58, ΔtssL, and various single, double, and triple toxin-immunity deletion strains.",
    "ncbi_link": "tssL: 1136207"
  },
  {
    "caption": "B. T6SS secretion assay of A. tumefaciens wild type C58, ΔtssL, Δtdei, and Δ3TIs harboring the indicated plasmids.",
    "ncbi_link": "tssL: 1136207"
  },
  {
    "caption": "A. T6SS secretion assay of A. tumefaciens 12D1 wild type, ΔtssL, and various toxin-immunity deletion strains.",
    "ncbi_link": "tssL: "
  },
  {
    "caption": "B. T6SS secretion assay of A. tumefaciens 12D1 wild type, ΔtssL, and various toxin-immunity deletion strains harboring the indicated plasmids.",
    "ncbi_link": "tssL: "
  },
  {
    "caption": "C. Antibacterial activity assay of A. tumefaciens 12D1 wild type, ΔtssL, and various toxin-immunity deletion strains harboring the indicated plasmids was carried out in a ratio of 30:1 against E. coli harboring the plasmid pRL662. The target E. coli cells were serially-diluted and grown overnight on gentamicin-containing LB agar prior to photographing. Each competition was done at least four times and reproduced in two independent experiments.",
    "ncbi_link": "tssL: "
  },
  {
    "caption": "D. T6SS secretion assay of A. tumefaciens C58 wild type, ΔtssL, and various mutant strains.",
    "ncbi_link": "tssL: 1136207"
  },
  {
    "caption": "B Identification of sec homozygotes. LB represents the left border primer of the T-DNA insertion. LP and RP represent the left and right genomic primers, respectively.",
    "ncbi_link": "sec: 819579"
  },
  {
    "caption": "C qRT-PCR analysis of SEC mRNA levels in sec-4 and sec-5 mutants. The expression level was normalized to that of TUBULIN, a reference gene for qRT-PCR. Independent biological experiments were repeated three times, and one representative result is shown here. Data shown are means ± standard deviation (s.d.), n = 3.",
    "ncbi_link": "sec-4: 
TUBULIN: 
SEC: 819579
sec-5: 838713///844020"
  },
  {
    "caption": "D The early flowering phenotype of sec-5 mutant under long-day (LD) conditions. Scale bar: 1 cm.",
    "ncbi_link": "sec-5: 838713///844020"
  },
  {
    "caption": "E qRT-PCR analysis of the expression levels of FLC, SOC1, and MAF1-3 in 12-d-old vegetative Col-0, sec-4 and sec-5 plants. Independent biological experiments were repeated three times, and one representative result is shown here. The expression level was normalized to that of TUBULIN. Data are means ± s.d., n = 3. (*), Statistical significance (two-tailed t-test) with P < 0.05.",
    "ncbi_link": "sec-4: 
TUBULIN: 
SOC1: 819174
FLC: 830878
MAF1: 844042
sec-5: 844020///838713"
  },
  {
    "caption": "F The sec-5 mutant exhibits an early flowering phenotype under short-day (SD) conditions. Scale bar: 1 cm.",
    "ncbi_link": "sec-5: 838713///844020"
  },
  {
    "caption": "G qRT-PCR analysis of FLC and SOC1 expression in Col-0 and sec-5 plants under SD conditions. The expression level was normalized to that of TUBULIN. Experiments were repeated three times, and one representative result is shown here. Data are mean ± s.d., n = 3. (*), Statistical significance (two-tailed t-test) with P < 0.05.",
    "ncbi_link": "TUBULIN: 
SOC1: 819174
FLC: 830878
sec-5: 844020///838713"
  },
  {
    "caption": "B ChIP-qPCR assay of H3K4me2 levels of indicated regions at FLC chromatin. C ChIP-qPCR assay of H3K4me3 levels of indicated regions at FLC chromatin. D ChIP-qPCR assay of H3K36me3 levels of indicated regions at FLC chromatin. E ChIP-qPCR assay of H3K27me3 levels of indicated regions at FLC chromatin .Data information: For ChIP analysis, 12-d-old plants were collected and three independent experiments were conducted. Each bar represents the mean ± s.d. of three independent experiments, n=3. The relative abundance was normalized to the input.",
    "ncbi_link": "FLC: 830878"
  },
  {
    "caption": "A Yeast two-hybrid assay of the interaction between ATX1 and SEC. The full-length coding sequence (CDS) of ATX1 was cloned into the bait vector pGBKT7. A full-length SEC CDS and a truncated fragment were cloned into the prey vector pGADT7 to express complete or truncated SEC-N (including only TPR domains at the N-terminus), respectively. AD vectors expressing SEC or SEC-N were each cotransformed with BD-ATX1. SD/2, SD/-Leu/-Trp medium; SD/4, SD/-Ade/-His/-Leu/-Trp medium. Cotransformed pGBKT7-53/pGADT7-T was used as a positive control.",
    "ncbi_link": "ATX1: 817721
SEC: 819579"
  },
  {
    "caption": "B Immunoblot analysis for O-GlcNAcylation of ATX1 by SEC using anti-CTD110.6 antibody. HA-tagged ATX1 was expressed alone or together with Flag-tagged SEC in tobacco leaves. Nuclear proteins were extracted from tobacco mesophyll cells, and expression of FLAG-SEC and ATX1-HA was confirmed by western blotting.",
    "ncbi_link": "Flag: 
HA: 
ATX1: 817721
SEC: 819579"
  },
  {
    "caption": "C Flowering phenotype of 35S::ATX1-HA overexpression transgenic lines in Col-0 and sec-5 backgrounds, respectively. Scale bar = 1 cm.",
    "ncbi_link": "HA: 
ATX1: 817721
sec-5: 844020///838713"
  },
  {
    "caption": "D Immunoblot analysis using anti-HA antibody to confirm ATX1-HA expression in Col-0 and 35S::ATX1-HA-overexpressing lines ACTIN was used as a loading control.",
    "ncbi_link": "HA: 
ATX1: 817721"
  },
  {
    "caption": "Flowering time phenotype analysis for Col-0, sec-5 and 35S::ATX1-HA transgenic lines Experiments were repeated three times, for each line, a total of 62 plants was counted for statistical analysis of rosette leaf numbers Data are mean ± s.d., (**), Statistical significance (two-tailed t-test) with P < 0.01. n.s., not significant.",
    "ncbi_link": "HA: 
ATX1: 817721
sec-5: 844020///838713"
  },
  {
    "caption": "Flowering time phenotype analysis for Col-0, sec-5 and 35S::ATX1-HA transgenic lines The percentages of plants with visible buds and the bolting rates were calculated on day 21 and day 24 after plant germination, respectively. Experiments were repeated three times, for each line, a total of 62 plants was counted for statistical analysis of visible buds percent and bolting rates. Data are mean ± s.d., (**), Statistical significance (two-tailed t-test) with P < 0.01. n.s., not significant.",
    "ncbi_link": "HA: 
ATX1: 817721
sec-5: 844020///838713"
  },
  {
    "caption": "C Analysis of ATX1 O-GlcNAc modification in wild-type and sec-5 plants. Total soluble protein extracts from 12-d-old seedlings were subjected to SDS-PAGE followed by immunoblotting using the indicated antibodies. CBB: Coomassie brilliant blue staining, showing relative protein loading amount.",
    "ncbi_link": "sec-5: 844020///838713"
  },
  {
    "caption": "D Loss of SEC function reduced ATX1 activity in Arabidopsis. Nuclear proteins were extracted and ATX1 was immunoprecipitated with anti-ATX1 antibody from wild-type and sec-5 mutant plants, respectively, and then used for histone H3K4 methyltransferase activity analysis with recombinant H3 as catalyzing substrate. Band intensities were quantified with Image J. The H3 signal was first normalized by input signal and then was used for H3K4me3 signal normalization.",
    "ncbi_link": "SEC: 819579
sec-5: 844020///838713"
  },
  {
    "caption": "E Comparison of ATX1 protein levels in Col-0 and sec-5 plants at stages before and after flowering. Seedlings were collected for protein extraction at 21 days (before flowering) and 35 days (after flowering) after seeds were planted on plates. Anti-ATX1 antibody was used for immunoblot assay.",
    "ncbi_link": "sec-5: 844020///838713"
  },
  {
    "caption": "A Mutation of either S947 alone or all 12 serine and threonine residues in the SET domain reduced O-GlcNAc modification level of ATX1ΔN.",
    "ncbi_link": "ATX1: 817721"
  },
  {
    "caption": "B Site mutation of S947 or all 12 serine and threonine residues in the ATX1 SET domain inhibited the activation of ATX1 by SEC; moreover, mutation of five conserved amino acids in the SEC functional domain inhibited SEC activity.",
    "ncbi_link": "ATX1: 817721
SEC: 819579"
  },
  {
    "caption": "A Flowering phenotypes of Col-0, atx1-2, atx1-2 35S::ATX1-FLAG, and atx1-2 35S::ATX1m-FLAG (with Ser947 replaced with alanine) plants under LD conditions. Scale bar: 1 cm. Two independent lines are shown for each transformation.",
    "ncbi_link": "FLAG: 
atx1: 817721
ATX1: 817721"
  },
  {
    "caption": "B Quantitative real-time PCR analysis of ATX1 and FLC transcript levels in Col-0, atx1-2, atx1-2 35S::ATX1-FLAG, and atx1-2 35S::ATX1m-FLAG plants. The transcript levels were normalized to that of TUBULIN. Data are mean ± s.d. of three independent biological replicates, n=3.",
    "ncbi_link": "FLAG: 
TUBULIN: 
ATX1: 817721
atx1: 817721
FLC: 830878"
  },
  {
    "caption": "IncuCyte cell proliferation curves for ASNS knockout (sgASNS) and control (sgNon-targeting) PC3 cells in the absence and presence of ASNase. Data information: For IncuCyte proliferation assays, images were taken every 4 hours and the cell confluence was calculated by averaging three mapped images per well. All results were calculated from three replicates and presented as mean ± SD, unless otherwise stated. The p-value was calculated by two-tailed unpaired t test by Prism7. **p<0.01, ***p<0.001. ",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "IncuCyte cell proliferation curves of SLC1A3 knockout (sgSLC1A3) and control (sgNon-targeting) PC3 cells in the absence and presence of ASNase treatment. #3 and #4 represent 2 different sgRNAs targeting SLC1A3. Data information: For IncuCyte proliferation assays, images were taken every 4 hours and the cell confluence was calculated by averaging three mapped images per well. All results were calculated from three replicates and presented as mean ± SD, unless otherwise stated. The p-value was calculated by two-tailed unpaired t test by Prism7. **p<0.01, ***p<0.001. ",
    "ncbi_link": "SLC1A3: 6507"
  },
  {
    "caption": "Radioactive labeled aspartate and glutamate uptake measurement in control (sgNon-targeting) and SLC1A3 knockout (sgSLC1A3) PC3 cells. #3 and #4 represent two different sgRNAs targeting SLC1A3. Radioactive labeled leucine uptake was used as a control. Data was normalized to the reads of control PC3 cells.",
    "ncbi_link": "SLC1A3: 6507"
  },
  {
    "caption": "Endogenous levels of aspartate, asparagine, glutamate and glutamine in control (sgNon-targeting) and SLC1A3 knockout (sgSLC1A3) PC3 cells with or without ASNase for 3 days. Median peak intensity was used for the read normalization.",
    "ncbi_link": "SLC1A3: 6507"
  },
  {
    "caption": "IncuCyte cell proliferation curves of SLC1A3 knockout (sgSLC1A3#3) PC3 cells treated with ASNase and supplemented with either esterified-aspartate (6mM) or esterified-glutamate (6mM), and esterified-leucine (6mM) as a control. Data information: For IncuCyte proliferation assays, images were taken every 4 hours and the cell confluence was calculated by averaging three mapped images per well. All results were calculated from three replicates and presented as mean ± SD, unless otherwise stated. The p-value was calculated by two-tailed unpaired t test by Prism7. **p<0.01, ***p<0.001. ",
    "ncbi_link": "SLC1A3: 6507"
  },
  {
    "caption": "RT-qPCR analysis was used to determine the relative SLC1A3 mRNA expression (to GAPDH) in different prostate and breast cancer cell lines, as indicated. Data information: Results were calculated based on three replicates (except for SUM159 and BT549 in B, n=2) and presented as mean ± SD. The p-value was calculated by two-tailed unpaired t test in Prism7. **p<0.01, ***p<0.001. a.u. indicates arbitrary unit.",
    "ncbi_link": "GAPDH: 2597
SLC1A3: 6507"
  },
  {
    "caption": "cell lines were transduced with either control (sgNon-targeting) or sgSLC1A3. Aspartate uptake levels were determined and compared between control and SLC1A3 KO in these cell lines. Leucine uptake level was used for normalization. The numbers above the control column denote the basal aspartate uptake capacity. Data information: Results were calculated based on three replicates (except for SUM159 and BT549 in B, n=2) and presented as mean ± SD. The p-value was calculated by two-tailed unpaired t test in Prism7. **p<0.01, ***p<0.001. a.u. indicates arbitrary unit.",
    "ncbi_link": "SLC1A3: 6507"
  },
  {
    "caption": "RT-qPCR was used to determine the relative mRNA levels (to GAPDH) of aspartate/glutamate transporter genes (SLC1A1, SLC1A2, SLC1A3, SLC1A6 and SLC1A7) in LNCaP, BT549 and SUM159PT cells. Data information: Results were calculated based on three replicates (except for SUM159 and BT549 in B, n=2) and presented as mean ± SD. The p-value was calculated by two-tailed unpaired t test in Prism7. **p<0.01, ***p<0.001. a.u. indicates arbitrary unit.",
    "ncbi_link": "GAPDH: 2597
SLC1A1: 6505
SLC1A2: 6506
SLC1A3: 6507
SLC1A6: 6511
SLC1A7: 6512"
  },
  {
    "caption": "MCF7 and DU145 cells were transduced with either lentiviral empty vector (control) or lentiviral vector containing a V5-tagged SLC1A3 coding sequence (V5-SLC1A3). Relative SLC1A3 mRNA levels (to GAPDH) were determined by RT-qPCR.",
    "ncbi_link": "V5: 
GAPDH: 2597
SLC1A3: 6507"
  },
  {
    "caption": "Relative aspartate uptake levels in control and V5-SLC1A3-expressed MCF7 and DU145 cells. Leucine uptake level was used for normalization.",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "Control and V5-SLC1A3 expressed MCF7 and DU145 cells were subjected to IncuCyte cell proliferation assays with or without ASNase at indicated concentrations.",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "PC3, DU145 and V5-SLC1A3-DU145 cells were subjected to ASNase and TFB-TBOA treatment at indicated concentrations and cell proliferation was measured by IncuCyte assay.",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "DU145 and V5-SLC1A3-DU145 cells were treated under indicated conditions with ASNase (0.2 U/ml) or TFB-TBOA (20μM) or both, and subjected to IncuCyte analysis for apoptotic cell counts.",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "A-C. PC3 (A), DU145 (B) and DU145-V5-SLC1A3 (C) cells were treated with ASNase (0.3 U/ml in A; 0.2 U/ml in B and C), TFB-TBOA (5 μM) for 3 days as indicated and subjected to transcriptome analysis. Bioinformatics pathway or gene ontology (GO) biological process analysis was performed on the sets of genes that were upregulated or downregulated when PC3 cells were treated with ASNase and TFB-TBOA compared to mock. Transcriptome analysis was based on one biological replicate for each cell line and validated by real-time PCR experiments in Figures EV4A-C. Heatmap presents row scaled normalized read counts and the biological signaling pathway enrichment analysis was performed by ToppGene online program",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "The mouse breast cancer cell lines 4T1 and 4T1-V5-SLC1A3 were orthotopically implanted into the mammary glands of pretreated NSG mice. Presented is the volume measurements of arising tumors at day 9. (n=13 mice for each group, except for 4T1+ASNase, n=12). Data are presented as mean ± SEM. Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "V5: 
SLC1A3: 20512"
  },
  {
    "caption": "The human breast cancer cell lines MDA-MB-231 and MDA-MB-231-V5-SLC1A3 cells were intravenously injected into pretreated NSG mice. Once mice showed breathing problems, they were sacrificed, and lung and liver were collected and blindly scored for metastasis lesions. The p-value was calculated by one-tailed unpaired t test in Prism7. Data are presented as mean ± SEM (n=8). Data information: The pretreatment started 2 days before the injection of cancer cells. And mice were either injected with 60 U ASNase or saline per day. The p-value was calculated by two-tailed unpaired t test in Prism7, unless otherwise stated. *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "V5: 
SLC1A3: 6507"
  },
  {
    "caption": "with digitonin and βHBP at indicated concentrations or digitonin and wt S. flexneri lysat C) TIFA oligomerization at 6 h in TIFA-GFP-expressing HeLa cells treate",
    "ncbi_link": "TIFA: 92610"
  },
  {
    "caption": "B) TIFA-GFP oligomerization at 30 min in HeLa cells treated with digitonin (mock) or digitonin and a lysate from indicated S. flexneri strains (pHldA/C means plasmid-encoded HldA and HldC)",
    "ncbi_link": "HldA: 
HldC: "
  },
  {
    "caption": "with digitonin (mock) or digitonin and a lysate from indicated S. flexneri strain (pHldA/C means plasmid-encoded HldA and HldC) C) TIFA-GFP oligomerization at 6 h in cells treate",
    "ncbi_link": "HldA: 
HldC: "
  },
  {
    "caption": "with digitonin (mock) or digitonin and a lysate from indicated S. flexneri strains (pHldA/C means plasmid-encoded HldA and HldC) D) IL-8 production at 6 h in cells were treate",
    "ncbi_link": "HldA: 
HldC: "
  },
  {
    "caption": "A) Representative images of the formation of TIFA oligomers in HeLa cells infected for 30 min with dsRed-expressing wt or indicated mutants of S. flexneri (MOI 50). pHldA/C means plasmid-encoded HldA and HldC. Fluorescence intensity was adjusted between strains to optimize visualization of bacteria. Scale bar, 20 μm",
    "ncbi_link": "HldA: 
HldC: "
  },
  {
    "caption": "A) ADP-heptose-induced TIFA-GFP oligomerization depends on ALPK1. After siRNA transfection, HeLa cells were transfected with empty pCMV or pCMV-ALPK1 as indicated. They were then infected with wt S. flexneri (MOI 10) or treated with digitonin and ADP-heptose (10-5 M) for 30 min. As control, cells were left untreated (mock) or treated with digitonin",
    "ncbi_link": "ALPK1: 80216"
  },
  {
    "caption": "ADP-heptose-induced cytokine secretion is ALPK1-dependent. HeLa cells were transfected with control or ALPK1-targeting siRNAs and infected with wt S. flexneri (MOI 2) or treated with ADP-heptose (10-5 M). As control, cells were left untreated (mock) or treated with digitonin. Cytokines were measured in cell culture supernatants after 8 h",
    "ncbi_link": "ALPK1: 80216"
  },
  {
    "caption": "A Whole mount immunofluorescence of a P8 Syne4-/- organ of Corti showing intact hair cells, as labelled with myosin VIIa. B Whole mount immunofluorescence of WT and Syne4-/- organ of Corti from the 8, 16, and 32 kHz regions at P8 and P14. ",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "C Inner and outer hair cell counts of Syne4-/- organ of Corti at P8, P10, P12, and P14.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "D FM1-43 uptake performed on P8+1 DIV (days-in-vitro) WT and Syne4-/- organ of Corti. Top shows OHC plane and bottom shows IHC plane.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "B Whole mount immunofluorescence of a P9 organ of Corti of a mouse injected with AAV.GFP at P1 showing complete transduction of both inner and outer HC. Myosin VIIa was used to label the hair cells. C Examples of 8, 16, and 32 kHz regions of an organ of Corti of a mouse injected with AAV.GFP. Top shows OHC plane, bottom shows IHC plane, right shows YZ orthogonal projection. Black asterisks show bright Deiters cells. D Quantification of GFP intensity of inner and outer HC from 3 injected mice, normalized to the average intensity of HC in a control, un-injected mouse. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "E Transduction rates of AAV9-PHP.B at 8, 16, and 32kHz regions based on GFP fluorescence. A total of 162 IHC and 841 OHC were analyzed from 3 injected mice and 1 control littermate.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "F Staining for FLAG at at P14 of the organ of Corti of a mouse injected at P1 with AAV.Syne4.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "H 3D surface projection of two adjacent OHC from a mouse injected with AAV.Syne4. In the left cell myosin VIIa and DAPI signals were removed to only show FLAG staining.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "A Whole-mount immunofluorescence of the 8 kHz region from P14 organ of Corti from WT, Syne4-/-, and Syne4-/- mice injected with AAV.Syne4. B 3D surface projection of IHC and OHC at P14 from the 8kHz region of WT, Syne4-/- mice and Syne4-/- mice injected with AAV.Syne4. Open arrows denote basal end, white arrows denote cuticular plate. ",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "D Quantification of nuclear distance from the cuticular plate. A total of 45 IHC and 135 OHC from 3 WT mice, 45 IHC and 81 OHC from 3 Syne4-/- mice, 30 IHC and 90 OHC from 2 Syne4-/- mice injected with AAV.Syne4 were measured.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "A Representative example of ABR traces obtained at 4w from a WT, Syne4-/- mouse, and Syne4-/- mouse injected with AAV.Syne4 in response to an 18 kHz stimulus.",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "B ABR thresholds at 4w of WT, Syne4-/-, Syne4-/- mice injected with AAV.Syne4, and Syne4-/- mice injected with AAV.GFP, n=7 for WT, n=8 for Syne4-/-, n=20 for Syne4-/- + AAV.Syne4, n=6 for Syne4-/- + AAV.GFP. C Quantification of P1-N1 amplitude delta from (B), n=4 for WT, n=4 for Syne4-/-, n=7 for Syne4-/- + AAV.Syne4. D Quantification of P1 latency from (B), n=4 for WT, n=2 for Syne4-/-, n=7 for Syne4-/- + AAV.Syne4. ",
    "ncbi_link": "GFP: 
GFP.: 
Syne4: 233066"
  },
  {
    "caption": "E DPOAE thresholds at 4w, n=6 for WT, n=5 for Syne4-/-, n=6 for Syne4-/- + AAV.Syne4. F ABR threshold at 12w, n=6 for WT, n=8 for Syne4-/-, n=16 for Syne4-/- + AAV.Syne4, n=5 for Syne4-/- + AAV.GFP. ",
    "ncbi_link": "GFP.: 
Syne4: 233066"
  },
  {
    "caption": "A Whole mount immunofluorescence at 12w of the organ of Corti of a Syne4-/- mouse injected with AAV.Syne4 mouse injected with AAV.Syne4. B Whole mount immunofluorescence at 12w of the 12 kHz region of WT, Syne4-/- mouse, and Syne4-/- mouse injected with AAV.Syne4. ",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "C IHC and OHC counts, n=3 for WT, n=4 for Mut, n=6 for Mut + AAV.Syne4. D Correlation between HC count and ABR threshold at 12kHz. ",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "E 3D surface projection of an OHC at 12w from the 12kHz region of WT and Syne4-/- mice injected with AAV.Syne4. Open arrows denote basal end, white arrows denote cuticular plate. F Image analysis of nucleus position of OHC. G Quantification of nuclear distance from the cuticular plate. A total of 30 OHC from 3 WT mice and 38 OHC from 4 Syne4-/- mice injected with AAV.Syne4 were measured. ",
    "ncbi_link": "Syne4: 233066"
  },
  {
    "caption": "B, C Quantification of activity level and cumulative freezing duration at 12w during seconds 90-210 of day 2 in WT, Syne4-/- mice, Syne4-/- mice injected with AAV.Syne4, and Syne4-/- mice injected with AAV.GFP, n=14 for WT, n=16 for Syne4-/-, n=9 for Syne4-/- + AAV.Syne4, n=5 for Syne4-/- + AAV.GFP. (C) Activity level. (B) Cumulative freezing duration.",
    "ncbi_link": "GFP: 
Syne4: 233066"
  },
  {
    "caption": "(A) Confocal images of representative eye cryosections immunostained with anti-Lamp1 antibody from 2-month-old miR-211-/- and control mice sacrificed 3h after light on, at 10 AM (diurnal condition). Enlarged boxes highlight Lamp1-positive structures (white arrowheads) in the RPE. Autofluorescence from lipofuscin granules are visible in all cryosections of miR-211-/- compared to control littermates. Nuclei were counterstained with DAPI (blue). At least n = 6 mice per group. Scale bar 10 μm. Data information: (RPE) Retinal Pigment Epithelium; (OS) outer segment; (ONL) outer nuclear layer.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(B) RPE were isolated at 10 AM (diurnal condition) from 2-month-old WT and miR-211-/- mice. Representative Western blot analysis of the Lamp1, Cln5, Trpml1, Sqstm1/p62, Cathepsin D (CtsD) and LC3 proteins from WT and miR-211-/- mice. Note a decrease of both proCtsD and its maturation CtsD heavy chain (hc). The plots show the quantification of the indicated proteins normalized to the Gapdh loading control. Bar graphs represent mean values ± s.e.m. of independent experiments (n=6 mice) Mann and Whitney test (miR-211-/- vs WT), *p ≤ 0.05, **p ≤ 0.01. Data information: (RPE) Retinal Pigment Epithelium",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(C) Cathepsin B (CtsB) activity in RPE lysates from 2-month-old miR-211-/- and control mice sacrificed 3h after light on at 10 AM (diurnal condition). CtsB was reduced in miR-211-/- compared to control mice. Bar graphs represent percentage of CtsB activity ± s.e.m. of independent experiments (n=3 mice) Mann and Whitney test (miR-211-/- vs WT), *p ≤ 0.05. Data information: (RPE) Retinal Pigment Epithelium",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(D) Representative images of conventional TEM analysis of RPE of both 2-month-old and 3-month-old WT and miR-211-/- mice. miR-211-/- mice show accumulation of phagolysosomes (red arrows) in the RPE. Scale bar 2 μm. Enlarged boxes highlight phagolysosome-like structures containing poorly processed POS. Scale bar 1.5 μm. Representative images of conventional TEM analysis of RPE shown at higher magnification also highlighted accumulation of lipofuscin-like granules (blue arrows) in 3-month-old miR-211-/- compared to control WT mice. Melanosomes are indicated by white asterisks. Scale bar 500 nm (n=3 mice). (E) Graphs showing number of lipofuscin-like granules (n/100 μm2) from the RPE of 3-month-old miR-211-/- mice as in (D). Bar graphs represent mean values ± s.e.m. Mann and Whitney test (miR-211-/- vs WT) ***p ≤ 0.005 (n=6 mice). Data information: (RPE) Retinal Pigment Epithelium",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(B) Graph representing the kinetic expression pattern of Ezrin levels in the RPE from 2-month-old WT mice during dark/light and light/dark transitions. Mice were sacrificed at determined time points as indicated on the X axis. Scheme at the top describes light/dark adaptation regime. Values normalized to Hprt, represent means ± s.e.m. Mann and Whitney test *p ≤ 0.05 (n=3 mice for each time point). Values from 12h dark-adapted mice (T0) were set to one.",
    "ncbi_link": "Ezrin: 22350
Hprt: 15452"
  },
  {
    "caption": "(C) Confocal images of representative eye cryosections immunostained with anti-Ezrin (green) and anti-ZO-1 (red) antibodies from 2-month-old miR-211-/- and WT control mice sacrificed 3h after light on at 10 AM (diurnal condition). Enlarged boxes highlight Ezrin staining in both basal infoldings (BI) and apical extension (AE) of the RPE. At least n = 6 mice per group. Scale bar 10 μm. Data information: (RPE) Retinal Pigment Epithelium; (OS) outer segment; (ONL) outer nuclear layer; (BI) RPE basal infoldings (AE) RPE apical extensions.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(D) qRT-PCR assay for Ezrin from RPE 2-month-old WT and miR-211-/- mice sacrificed 3h after light on at 10 AM. The graph shows the expression level of Ezrin normalized to Hprt. Bar graphs represent mean values ± s.e.m. Mann and Whitney test (miR-211-/- vs WT), ***p ≤ 0.005 (n=6 mice).",
    "ncbi_link": "Ezrin: 22350
Hprt: 15452
miR-211: 387207"
  },
  {
    "caption": "(E) RPE were isolated at 10 AM (diurnal condition) from 2-month-old WT and miR-211-/- mice. Representative image at low exposure of Western blot analysis of the Ezrin protein from WT and miR-211-/- mice. The graph shows the quantification of Ezrin normalized to the Gapdh loading control. Bar graphs represent mean values ± s.e.m. of independent experiments (n=5 mice) Mann and Whitney test (miR-211-/- vs WT), **p ≤ 0.01.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(F) Graph representing the kinetic expression pattern of Ezrin levels in the RPE from 2-month-old miR-211-/- mice during dark/light and light/dark transitions. Mice were sacrificed at determined time points as indicated in X axis. Scheme at the top describes light/dark adaptation regime. Values normalized to Hprt, represent means ± s.e.m. (n=3 mice for each time point). Values from 12h dark adapted mice (T0) were set to one. (G) Graph representing the kinetic expression pattern of Trpm1 levels in the RPE from 2-month-old WT mice during dark/light and light/dark transitions. Mice were sacrificed at determined time points as indicated in X axis. Scheme at the top describes light/dark adaptation regime. Values normalized to Hprt, represent means ± s.e.m (n=3 mice for each time point). Values from 12h dark adapted mice (T0) were set to one. ",
    "ncbi_link": "Ezrin: 22350
Hprt: 15452
miR-211: 387207
Trpm1: 17364"
  },
  {
    "caption": "(H) qRT-PCR assay for Mtmr10 and Klf13 from RPE 2-month-old WT and miR-211-/- mice sacrificed 3h after on at 10 AM. The graph shows the expression level of these genes normalized to the Hprt. Bar graphs represent mean values ± s.e.m. (n=3 mice)",
    "ncbi_link": "Hprt: 15452
Klf13: 50794
miR-211: 387207
Mtmr10: 233315"
  },
  {
    "caption": "(D) Representative images of RFP-GFP-LC3 assay in ARPE-19 cells transiently transfected with RFP-GFP-LC3 and treated with DMSO or NSC668394. Nuclei were counterstained with DAPI (blue). Scale bars: 5 μm. (E) Box plots showing quantitative analysis of RFP+GFP+ puncta (Autophagosome) and RFP+GFP- puncta (Autolysosome ) (n ≥ 100 cells) from 3 independent experiments. Box limits represent 25th percentile and 75th percentile; horizontal lines represent medians; whiskers display min. to max. values. Student's t-test (NSC668394 vs DMSO) *p ≤ 0.05.",
    "ncbi_link": "GFP: 
RFP: 
LC3: 66734///67443"
  },
  {
    "caption": "(A) Representative images from HC assay of HeLaTFEB-GFP cells transfected with control (siCTRL) or siPPP3CB, and subjected to the indicated conditions. Analysis of TFEB nuclear translocation in HeLaTFEB-GFP cells transfected with siCTRL or siPPP3CB and treated with DMSO or NSC668394, silenced for EZRIN (siEZR) or serum-starved (stv). Both pharmacological inhibition and silencing of Ezrin induced TFEB nuclear localization in stable HeLaTFEB-GFP cells. Starvation (stv) was used as control. Nuclear translocation of TFEB in stable HeLaTFEB-GFP cells subjected to the indicated conditions is rescue after silencing of PPP3CB. Scale bar 5 μm.",
    "ncbi_link": "GFP: 
EZRIN: 7430
EZR: 7430
PPP3CB: 5532
TFEB: 7942"
  },
  {
    "caption": "(B) The graph shows the mean ± s.e.m. of the percentage of nuclear TFEB translocation in Ezrin-inhibited cells compared to control; n=3 independent experiments were performed. Mann and Whitney test (NSC668394 and stv vs DMSO; siEZR vs siCTRL) *p ≤ 0.05.",
    "ncbi_link": "EZR: 7430"
  },
  {
    "caption": "(C) The graph shows the mean ± s.e.m. of the percentage of nuclear TFEB translocation in Ezrin-inhibited cells and subjected to the silencing of PPP3CB. At least 3 independent experiments were performed. Mann and Whitney test (siPPP3CB vs siCTRL) *p ≤ 0.05.",
    "ncbi_link": "PPP3CB: 5532"
  },
  {
    "caption": "(D) qRT-PCR assay for PPP3CB from HeLaTFEB-GFP cells transfected with siPPP3CB and siCTRL. The graph shows the reduction in PPP3CB expression level normalized to the Hprt. Bar graphs represent mean values ± s.e.m. Mann and Whitney test (siPPP3CB vs siCTRL), ***p ≤ 0.005 (n=6 independent experiments).",
    "ncbi_link": "GFP: 
Hprt: 3251
PPP3CB: 5532
TFEB: 7942"
  },
  {
    "caption": "(E) Both pharmacological inhibition and silencing of EZRIN induce downshift of endogenous TFEB electrophoretic mobility in Western blot analysis. Torin treatment was used as control.",
    "ncbi_link": "EZRIN: 22350"
  },
  {
    "caption": "(G) Nuclear translocation of TFEB in stable HeLaTFEB-GFP cells subjected to the indicated conditions is reduced after Ca2+ chelator BAPTA treatment. Scale bar 5 μm.",
    "ncbi_link": "GFP: 
TFEB: 7942"
  },
  {
    "caption": "(I) qRT-PCR analysis for TFEB target genes (TRPML1, BECLIN, MAPLC3B and LAMP1) was performed on ARPE-19 cells treated with DMSO or NSC668394. Bar graphs represent mean values ± s.e.m. of at least 3 independent experiments. Mann and Whitney *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.005.",
    "ncbi_link": "BECLIN: 8678
MAPLC3B: 81631
TRPML1: 57192
TFEB: 7942"
  },
  {
    "caption": "(A) Confocal images of representative eye cryosections immunostained with anti-Ezrin (green) /anti-ZO-1 (red), anti-Ezrin-pT567 (green) /anti-ZO-1 (red), anti-Lamp1 (green) and anti-Sqstm1/p62 (green) antibodies from 6-month-old miR-211-/- sacrificed five months after DMSO or NSC668394 treatment. Nuclei are counterstained with DAPI (blue). At least n = 6 mice per group. Scale bar 100 μm. Data information: (RPE) Retinal Pigment Epithelium; (OS) outer segment; (ONL) outer nuclear layer.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(B) RPE was isolated 5 months after DMSO or NSC668394 treatment from 6-month-old miR-211-/- mice. Representative Western blots proteins from these tissues were performed to determine the expression levels of Lamp1, Ezrin, Ezrin-pT567, Sqstm1/p62 and LC3. The plots show the quantification of the indicated proteins normalized to the β-Actin loading control. Bar graphs represent mean values ± s.e.m. of independent experiments (n=6 mice). Mann and Whitney test (DMSO vs WT; NSC668394 vs DMSO), *p ≤ 0.05, ***p≤0.005.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(C) Cathepsin B (CtsB) activity in RPE lysates from miR-211-/- and WT mice sacrificed 3h after light on at 10 AM (diurnal condition). RPE was isolated 1 week after DMSO or NSC668394 treatment from 2-month-old miR-211-/- mice. CtsB was rescued in NSC668394-treated miR-211-/- compared to DMSO-control miR-211-/- mice. Bar graphs represent percentage of CtsB activity ± s.e.m. of independent experiments (n=3 mice) Mann and Whitney test (DMSO-miR-211-/- vs WT; NSC668394-miR-211-/- vs DMSO-miR-211-/-), *p ≤ 0.05. (D) GUSB activity from retina from miR-211-/- and control mice sacrificed 3h after light on at 10 AM (diurnal condition). Retina was isolated 1 week after DMSO or NSC668394 treatment from 2-month-old miR-211-/- mice. GUSB was rescued in NSC668394-treated miR-211-/- compared to DMSO-control miR-211-/- mice. Bar graphs represent percentage of GUSB activity ± s.e.m. of independent experiments (n=3 mice). Mann and Whitney test (DMSO-miR-211-/- vs WT; NSC668394-miR-211-/- vs DMSO-miR-211-/-).",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(A) Representative images of conventional TEM analysis of RPE of WT, DMSO-treated miR-211-/- mice and NSC668394-treated miR-211-/- three-month-old mice. NSC668394-treated miR-211-/- mice show rescue of accumulation of double-membrane phagolysosome-like structures containing poorly processed POS (red arrows) compared to DMSO-treated miR-211-/- mice. Scale bar 1 mm. Data information: (OS) outer segment (RPE) Retinal Pigment Epithelium.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(B) Confocal images of representative eye cryosections immunostained with anti-Rhodopsin (green) antibody from WT and miR-211-/- mice at three months of age after DMSO or NSC668394 treatment, which are sacrificed 3h after light on at 10 AM (diurnal condition). Nuclei are counterstained with DAPI (blue). At least n = 6 mice per group. Scale bar 100 μm. The enlarged box highlights rhodopsin accumulation in the RPE (green spots). Scale bar 5 μm. Autofluorescence from lipofuscin granules from WT and miR-211-/- mice at three months of age after DMSO or NSC668394 treatment. Representative images of retina cryosections immunostained with anti-Cone Arrestin (green) antibody from WT and miR-211-/- mice at three months of age after DMSO or NSC668394 treatment. Nuclei are counterstained with DAPI (blue). N = at least 6 mice per group. Scale bar 100 μm. Data information: (OS) outer segment; (ONL) outer nuclear layer; (RPE) Retinal Pigment Epithelium.",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(C) Graphs showing number of lipofuscin granules from the RPE of mice as in (B). Bar graphs represent mean values ± s.e.m. Mann and Whitney test (miR-211-/- DMSO vs WT and miR-211-/- NSC668394 vs DMSO treated mice) ***p ≤ 0.005. *p ≤ 0.05 (n=6 mice).",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "(E) Representative flicker traces at three months of age show the rescue of flicker responses of NSC668394-treated miR-211-/- mice (green lines) compared to DMSO-treated miR-211-/- control mice (red lines). WT mice were used as a control (black lines). Flicker recordings were performed with light intensities ranging from 10−4 to 15 cd s/m2 in steps of 0.6 logarithmic units at 6 Hz frequency. (F) Flicker responses, plotted as a function of stimulus intensity, from WT (black lines), DMSO-treated miR-211-/- (red lines) and NSC668394-treated miR-211-/- (green lines) mice, at three months of age. The amplitude of the recordings from NSC668394 miR-211-/- treated mice is significantly rescued compared to DMSO-treated miR-211-/- mice. WT mice were used as a control. Error bars represent s.e.m. ANOVA test (DMSO vs WT and NSC668394 vs DMSO treated mice) **p ≤ 0.01, ***p ≤ 0.005. ",
    "ncbi_link": "miR-211: 387207"
  },
  {
    "caption": "Representative confocal micrographs of co-cultures of wild-type (WT) and ZO-1/-2 double knockout (DKO) Eph4 cells. ZO-1/-2 DKO cells were marked by asterisks (*). The LUZP1 junctional localization was apparently disrupted in TJ-deficient ZO-1/-2 DKO cells. Scale bar, 10 μm.   Representative confocal micrographs of transient E-cadherin knockout (KO) in WT Eph4 cells. E-cadherin KO cells were marked by asterisks (*). The LUZP1 junctional localization seemed not to change between AJ-deficient E-cadherin KO and WT cells. Scale bar, 10 μm.   ",
    "ncbi_link": "E-cadherin: 12550
ZO-1: 21872"
  },
  {
    "caption": "Bar plots with dot density plots showing that ppMLC levels within CRs were significantly reduced in LUZP1 KO cells compared to those in WT cells [19.19 ± 10.02 arbitrary units (a.u.) (WT) vs. 2.92 ± 1.81 a.u. (LUZP1 KO)]. n = 3. **p < 0.01 (Mann-Whitney U test). Bars and error bars represent the mean ± SD.",
    "ncbi_link": "LUZP1: 269593"
  },
  {
    "caption": "Representative confocal micrographs of co-cultures of wild-type (WT) and ZO-1/-2 double knockout (DKO) Eph4 cells. ppMLC levels within CRs were clearly reduced in ZO-1/-2 DKO cells compared to those in WT cells. Scale bar, 10 μm.   Bar plots with dot density plots showing that apical areas of WT cells were significantly smaller than those of ZO-1/-2 DKO cells [119.62 ± 31.62 μm2 (WT) vs. 199.96 ± 94.22 μm2 (LUZP1 KO)] (See also Fig 1I). n = 3. **p < 0.01 (unpaired t test). Bars and error bars represent the mean ± SD.   ",
    "ncbi_link": "LUZP1: 269593
ZO-1: 21872"
  },
  {
    "caption": "Representative immunoblot of WT, LUZP1 KO, and Venus-LUZP1-expressing LUZP1 knockout (REV) Eph4 cells treated with 100 nM calyculin A for 30 min. Quantification of the ppMLC/MLC ratio relative to WT control, confirming the reversal of the difference in ppMLC levels within CRs between WT and LUZP1 KO cells by calyculin A [WT, 1.00 (control) vs. 1.40 ± 0.06 (calyculin A) vs. 1.14 ± 0.33 (washout); KO, 0.09 ± 0.04 (control) vs. 1.49 ± 0.06 (calyculin A) vs. 0.81 ± 0.99 (washout); REV, 2.06 ± 1.78 (control) vs. 1.82 ± 1.50 (calyculin A) vs. 1.80 ± 1.14 (washout)]. n = 3. Bars and error bars represent the mean ± SD.",
    "ncbi_link": "LUZP1: 269593"
  },
  {
    "caption": "Box plots with dot density plots showing the ratio of the apical area/basal area in co-cultures of Venus-LUZP1-expressing LUZP1 knockout (REV) and LUZP1 knockout (LUZP1 KO) Eph4 cells; 2 μM nocodazole treatment for 30 min partially reversed apical constriction of REV cells [REV, 0.65 ± 0.16 (control) vs. 0.90 ± 0.18 (nocodazole) vs. 0.64 ± 0.16 (washout); KO, 1.30 ± 0.17 (control) vs. 1.07 ± 0.13 (nocodazole) vs. 1.32 ± 0.19 (washout)]. **p < 0.01 (Kruskal-Wallis test followed by Steel-Dwass test). The solid lines represent the medians and the boxes represent the inter-quartile ranges. The error bars extending from the box represents the data within 1.5 times of the interquartile range. Representative confocal micrographs of co-cultures of LUZP1-expressing wild-type (WT) and LUZP1 KO Eph4 cell treated with 2 μM nocodazole for 30 min. Nocodazole treatment partially reversed the difference in di-phosphorylated MLC (ppMLC) levels within circumferential rings (CRs) between WT and LUZP1 KO cells. Scale bar, 10 μm.   Bar plots with dot density plots showing that ppMLC levels within CRs were significantly down-regulated in WT Eph4 cells after nocodazole treatment. Importantly, ppMLC levels in LUZP1 KO Eph4 cells were unchanged after nocodazole treatment [WT, 21.43 ± 6.96 arbitrary units (a.u.) (control) vs. 17.67 ± 5.40 a.u. (nocodazole) vs. 20.84 ± 7.19 a.u. (washout); KO, 8.74 ± 1.71 a.u. (control) vs. 8.67 ± 1.89 a.u. (nocodazole) vs. 7.96 ± 2.35 a.u. (washout)]. n = 3. **p < 0.01 (Kruskal-Wallis test followed by Steel-Dwass test). Bars and error bars represent the mean ± standard deviation (SD).   ",
    "ncbi_link": "LUZP1: 269593"
  },
  {
    "caption": "(a,b) Bacteria in the spleens of Slamf1−/−Rag1−/− and Rag1−/− BALB/c mice (a) or Slamf1−/− and Slamf1+/+ BALB/c mice (b) 48 h after intraperitoneal injection of virulent S. typhimurium 14028s or attenuated S. typhimurium SseB−. CFU, colony-forming units; ND, not detectable. Data are representative of four independent experiments (mean and s.d.).",
    "ncbi_link": "Rag1: 19373
Slamf1: 27218"
  },
  {
    "caption": "(c-e) Killing of bacteria by peritoneal macrophages from Slamf1+/+ and Slamf1−/− BALB/c mice exposed to S. typhimurium SseB− (c), E. coli F18 (d) or S. aureus (e), assessed by gentamycin assay. Data are representative of five independent experiments (mean and s.d.).",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(f) Uptake of bacteria by Slamf1+/+ (red solid lines) or Slamf1−/− (black solid lines) BALB/c peritoneal macrophages incubated at 37 °C with E. coli-eGFP or S. typhimurium-eGFP or by Slamf1+/+ macrophages incubated for 60 min at 4 °C with the bacteria (dotted lines). Right, mean fluorescence intensity (MFI). Data are representative of three independent experiments (mean and s.d.).",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(a) NOX2 activity in Slamf1+/+ and Slamf1-/- BALB/c peritoneal macrophages stimulated for 0-100 min with E. coli F18, S. aureus or PMA, assessed with lucigenin. Data are representative of five independent experiments (mean ± s.d.).",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(b) Phagosomal pH of Slamf1+/+, Slamf1-/- and gp91phox-/- B6 primary macrophages loaded for 0-200 min with pHrodo-coated E. coli or S. aureus, analyzed by flow cytometry. Data are representative of three independent experiments (mean ± s.d.).",
    "ncbi_link": "gp91phox: 13058
Slamf1: 27218"
  },
  {
    "caption": "(c) NOX2 activity in primary macrophages in response to LPS, purified OmpC, peptidoglycan (PGN) or PMA, assessed with lucigenin. TLR4-KO, TLR4-deficient (strain del/Jtht; C3H). Data are representative of five independent experiments (mean ± s.d.).",
    "ncbi_link": "TLR4: 21898"
  },
  {
    "caption": "(a) Fluorescence microscopy of E. coli-containing phagosomes in primary macrophages transfected with RFP-conjugated LAMP-1, showing colocalization with E. coli-eGFP or S. aureus-eGFP. Right, quantification of LAMP-1+ phagosomes in the microscopy at left.",
    "ncbi_link": "LAMP-1: 16783"
  },
  {
    "caption": "(b) Immunoblot analysis of LAMP-1 in phagosomes isolated by sucrose-gradient flotation from RAW264.7 macrophages after phagocytosis by Slamf1- or mock-transfected RAW264.7 macrophages of beads coated with E. coli outer membrane extract. WCL, whole-cell lysate. Right, quantification of LAMP-1 in the immunoblot at left.",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(c) Localization of MHC class II-eGFP (MHCII GFP) in phagosomes of primary macrophages from Slamf1+/+ or Slamf1−/− MHC class II-eGFP (B6) mice and 3-μm beads coated with E. coli outer membrane extract. (d) Entry of 3-μm beads coated with E. coli outer membrane extract into lysosomes loaded with Texas red-dextran. Right (c,d), quantification of fluorescence in the microscopy at left. Numbers in bottom right corners (a,c,d) indicate time (in min). Original magnification (a-c), ×60. DIC, differential interference contrast. Data are representative of three combined experiments (a) or at least three independent experiments (b-d) with at least 100 beads or 80 bacteria in each (error bars, s.d.).",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(b) Immunoblot analysis of phagosome isolates from RAW264.7 macrophages transiently transfected with cDNA encoding Myc-tagged SLAM (Slamf1-Myc) or mock transfected and allowed to phagocytose beads coated with E. coli outer membrane extract for 60 or 120 min. kDa, kilodaltons. Data are representative of at least three independent experiments.",
    "ncbi_link": "Slamf1: 27218"
  },
  {
    "caption": "(a) Luciferase activity in Jurkat cells transfected with a fusion of SLAM and CD3ζ and a luciferase reporter (as described in Results), plus a renilla luciferase reporter, then exposed to heat-killed bacteria (top).",
    "ncbi_link": "luciferase: 
renilla: 
CD3ζ: 919
SLAM: 6504"
  },
  {
    "caption": "(b) Luciferase activity in Jurkat cells transfected with the fusion in a (Slamf1-CD3ζ) or a fusion of SLAM ectodomain construct lacking the immunoglobulin V domain and CD3ζ (ΔIgV-Slamf1-CD3ζ), and luciferase reporters as in a, then exposed to heat-killed E. coli F18.",
    "ncbi_link": "luciferase: 
CD3ζ: 919
Slamf1: 6504"
  },
  {
    "caption": "(c) Luciferase activity in Jurkat cells transfected as in a, then left uninoculated (−) or inoculated with 10 × 108 E. coli F18 (+), followed by the addition of monoclonal antibody (mAb; amount, under graph) 9D1 to SLAM (α-SLAM) or rat immunoglobulin G2b isotype-matched control antibody (Rat IgG2b).",
    "ncbi_link": "SLAM: 6504"
  },
  {
    "caption": "(a,b) Production of phagosomal PtdIns(3)P in E. coli-containing phagosomes of primary peritoneal macrophages transfected with reporter cDNA encoding an eGFP-tagged PX domain of p40phox (p40 PX-eGFP) and treated with DsRed-expressing E. coli (E. coli-DsRed; a) or beads coated with E. coli outer membrane extract (b). Numbers in bottom right corners indicate time (in min). Original magnification, ×60. Right, quantification of fluorescence in microscopy at left.",
    "ncbi_link": "p40 PX: 17972
p40phox: 17972"
  },
  {
    "caption": "(d) PtdIns(3)P production in RAW264.7 cells stably expressing SLAM or a mock construct, transfected with eGFP-tagged p40 PX and treated with beads coated with E. coli outer membrane extract. Data are from three combined experiments (a) or are representative of at least three independent experiments (b,d) or two independent experiments (c) with at least 100 beads or bacteria per experiment (error bars, s.d.).",
    "ncbi_link": "p40 PX: 17972
SLAM: 27218"
  },
  {
    "caption": "(a,b) Immunoassay of 293 cells transfected with various combinations of full-length SLAM (a) or hemagglutinin-tagged (-HA) tail-less SLAM (b), EAT-2A, V5-tagged (-V5) Vps34-Vps15, and beclin-1; proteins immunoprecipitated (IP) from lysates with monoclonal antibody to SLAM, as well as whole-cell lysates (WCL), were analyzed by immunoblot (IB) with anti-beclin-1, anti-Vps34, anti-V5, anti-hemagglutinin, anti-SLAM or anti-EAT2.",
    "ncbi_link": "beclin-1: 8678
Vps34: 5289
Vps15: 30849
EAT-2A: 117157
SLAM: 6504"
  },
  {
    "caption": "(c) Microscopy of RAW264.7 cells transiently transfected with cDNA encoding GFP-tagged beclin-1 and SLAM-mCherry, then treated with beads coated with E. coli outer membrane extract (at a ratio of 10:1, beads/cells) and fixed after 60 min. Data are representative of six (a) or two (b,c) independent experiments.",
    "ncbi_link": "beclin-1: 56208
SLAM: 27218"
  },
  {
    "caption": "CTLs exhibit extensive differences in lytic activity in vivo. Mice with established B cell lymphoma expressing OVA and the caspase 3 reporter were adoptively transferred with LifeAct-GFP-expressing  OT-I CTLs. Intravital imaging of the  bone marrow was performed two days after T cell transfer. (E) Representative  two-photon time-lapse images showing a representative CTL with high lytic capacity (killing 4 targets) and a  CTL with no lytic activity  for up to 4 hours. Blue arrows mark  apoptotic  tumor cells. Live and apoptotic tumors appear in grey and blue, respectively. CTLs  appear in green. Scale bar, 10 µm. Representative of 3 independent experiments.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) Top: SERA6 architecture. Positions of the papain-like domain, catalytic triad residues, SUB1 cleavage sites and epitopes for the antibodies used are indicated. Positions of the inserted mTAP or myc3 epitope tags (between codons Asn886-Val887) introduced in SERA6-mTAP:loxP parasites are shown. Bottom: time-course analysis of egress by western blot, showing processing of SERA6-mTAP into multiple protein species (representative of 2 independent experiments). Schizonts were sampled at the indicated times following washout of C2-mediated arrest. Nomenclature for each protein species was based on apparent molecular mass or predicted composition. Note that the predicted mass of the p40 species is ~27 kDa, but its migration on SDS PAGE may be aberrant due to its acidic nature; the predicted pI of sequence between SUB1 site 1 and the central papain-like domain (Asp371-Lys605) is ~4.4 (see https://web.expasy.org/compute_pi/).",
    "ncbi_link": "mTAP: 
SERA6: 812667"
  },
  {
    "caption": "(C) Giemsa-stained thin films and western blot of DMSO- and RAP-treated SERA6-WT-myc3 [SERA6-mTAP:loxP] and SERA6-Cys644Ala-myc3 [SERA6-mTAP:loxP] parasites showing that cleavage of host RBC β-spectrin (red arrowhead) does not occur unless a functional copy of SERA6 is present, and is tightly associated with egress (reproducible in 2 independent experiments). Schizonts were sampled at the indicated times following washout of C2. Scale bar, 5 μm. Also see Fig EV2.",
    "ncbi_link": "mTAP: 
myc3: 
SERA6: 812667"
  },
  {
    "caption": "(A) Replication of DMSO- and RAP-treated MSA180-HA3:loxP parasites over three erythrocytic cycles. Parasitaemia values are averages from replicates in different blood sources. The similar growth rate of DMSO-treated parasites and the parental B11 clone shows that the genetic modifications to generate MSA180-HA3:loxP parasites did not affect parasite viability. Error bars, ± S.D (B11: n=3; DMSO- and RAP-treated MSA180-HA3:loxP: n=6 each).",
    "ncbi_link": "HA3: 
MSA180: 810296"
  },
  {
    "caption": "(D) Time-course comparing fate of SERA6 from DMSO- and RAP-treated MSA180-HA3:loxP parasites (representative of 2 independent experiments). Schizonts were sampled at the indicated times following removal of C2-arrest, or arrested with E64-d (50 μM). RAP-treated SERA6-Cys644Ala-myc3 [SERA6-mTAP:loxP] parasites were included in the blot to allow comparison with processing of catalytically-dead SERA6 (SERA6-Cys644Ala-myc3). Note the accumulation of SERA6 p65 and poor conversion to SERA6 p40 in the RAP-treated (ΔMSA180) parasites.",
    "ncbi_link": "HA3: 
mTAP: 
myc3: 
SERA6: 812667
MSA180: 810296"
  },
  {
    "caption": "(A) Representative IFA images demonstrating the dynamic changes in localisation of SERA6-mTAP during egress (reproducible in 4 independent experiments). SERA6-mTAP:loxP schizonts were sampled at the indicated times following removal of C2-arrest, fixed and co-stained with DAPI (blue), anti-HA (red) and anti-ankyrin (green; ankyrin is a major component of the RBC cytoskeleton). Scale bar, 5 μm.",
    "ncbi_link": "mTAP: 
SERA6: 812667"
  },
  {
    "caption": "(C) Representative IFA images demonstrating localisation of MSA180-HA3 during egress. MSA180-HA3 [B11] schizonts were sampled at the indicated times following removal of C2-arrest, fixed and co-stained with DAPI (blue), anti-HA (red) and anti-ankyrin (green). Scale bar, 5 μm. See also Fig EV5.",
    "ncbi_link": "HA3: 
MSA180: 810296"
  },
  {
    "caption": "(C) Western blot comparing dose-response of E64-d, MMV676881 and Compound 31-mediated inhibition of maturation of SERA6-mTAP from SERA6-mTAP:loxP parasites (reproducible in 3 independent experiments).",
    "ncbi_link": "mTAP: 
SERA6: 812667"
  },
  {
    "caption": "a, Percentage of ciliated cells in control (Ctrl) and IFT20− MEFs (*P = 0.030, n = 3) and wild-type (WT) and Ift88−/− KECs (**P = 0.003, 25 cells each, n = 3) after 24 h of serum removal. Arrows, cilia.",
    "ncbi_link": "IFT20: 55978
Ift88: 21821"
  },
  {
    "caption": "b, LC3 immunoblot (left) for autophagic flux quantification (right) in Ctrl and IFT20− MEFs (top, **P = 0.0003, n = 7), and in WT and Ift88−/− KECs (bottom, *P = 0.035, n = 9). PI, protease inhibitors; S, serum. c",
    "ncbi_link": "IFT20: 55978
Ift88: 21821"
  },
  {
    "caption": "c, Autophagic flux in WT and Ift88−/−KECs by mCherry-GFP-LC3 puncta quantification. Puncta: yellow, autophagosomes; red only, autophagolysosomes; total, both together (**P = 0.008, *P = 0.025).",
    "ncbi_link": "Ift88: 21821"
  },
  {
    "caption": "e, Electron microscopy images (left) and morphometric quantification of autophagic vacuoles (AV, right) in Ctrl and IFT20− MEFs (top, **P = 0.001, 10 fields in 2 experiments) and KECs WT and Ift88−/− (bottom, *P = 0.037, 5 fields). Arrows, autophagic vacuoles (AV, black) and endosomal compartments (yellow).",
    "ncbi_link": "IFT20: 55978
Ift88: 21821"
  },
  {
    "caption": "a, GFP-LC3 puncta pattern (left) and quantification (right) in MEFs treated with purmorphamine (Purmo; top, *P = 0.028, n = 4), in Ptc−/− MEFs (middle, *P = 0.015, n = 4) and after myc-GLI1 overexpression (bottom, *P = 0.012, n = 3).",
    "ncbi_link": "GLI1: 14632
Ptc: 19206"
  },
  {
    "caption": "c, LC3 immunoblot (left) for autophagic flux quantification (right) in Ctrl (**P = 0.001) and MEFs knocked down for SMO (SMO−) (**P = 0.0001) upon purmorphamine treatment (*P = 0.009, n = 4).",
    "ncbi_link": "SMO: 319757"
  },
  {
    "caption": "d, Autophagic flux by mCherry-GFP-LC3 puncta quantification in WT and Ift88−/− KECs upon purmorphamine treatment (*P = 0.046, **P = 0.008, 40 fields).",
    "ncbi_link": "Ift88: 21821"
  },
  {
    "caption": ". e, LC3 immunoblot (left) for autophagic flux quantification (right) in Ift88−/− KECs overexpressing myc-GLI1 (**P = 0.00006, n = 3).",
    "ncbi_link": "GLI1: 14632
Ift88: 21821"
  },
  {
    "caption": "d-f, Percentage of cells with colocalizing ATGs in the basal body (BB) in WT and Ift88−/− KECs in the presence or absence of serum. d, Serum- and IFT-dependent association of ATGs with the BB (VPS34, †P = 0.04, **P = 0.002, n = 4; ATG16L, ††P = 0.0003, **P = 0.0009, 15 cells each per experiment, n = 7). e, IFT-dependent but serum-independent association of ATGs with the BB (**P = 0.001, ***P = 9.33768 × 10−6, n = 4; *P = 0.018, 15 cells each per experiment, n = 5). f, BB association of ATGs independent on serum or IFT (ATG5, n = 5; LC3, n = 8; 15 cells each per experiment). Scale bars, 10 &mgr;m. Mean ± s.e.m.",
    "ncbi_link": "Ift88: 21821"
  },
  {
    "caption": "a, b, Immunoblot for the indicated proteins of WT and Ift88−/− KECs subjected to co-immunoprecipitation of IFT20 (a) and ATG16L (b). Inp, 1/10 input; IP, immunoprecipitate; FT, 1/10 flow-through.",
    "ncbi_link": "Ift88: 21821"
  },
  {
    "caption": "d, Immunoblot for IFT20 and ATG16L in the same fractions isolated from Ctrl, IFT20− and IFT88− MEFs in the presence (top) and absence (bottom) of serum.",
    "ncbi_link": "IFT20: 55978
IFT88: 21821"
  },
  {
    "caption": "a, b, Ciliated Atg5−/− MEFs in serum+ (*P = 0.038, 25 cells each per experiment, n = 3) (a) or serum− (*P = 0.006, nonlinear fit regression, 25 cells each per experiment, n = 3) (b).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "e, f, GLI1 (*P = 0.04, n = 3) (e) and GLI2 (***P = 0.0005, **P = 0.0046, †P = 0.0132, n = 3) (f) messenger RNA expression in Atg5−/− MEFs.",
    "ncbi_link": "Atg5: 11793
GLI1: 14632
GLI2: 14633"
  },
  {
    "caption": "g, h, IFT20 immunoblot in Atg5−/− (g) and WT MEFs with lysosomal inhibitors (NL) (h).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "i, IFT20 immunoblot in cytosol (Cyt), homogenate (Hom) and autophagosomes (APG). j, IFT20 protein levels in Atg5−/− MEFs (*P = 0.038, n = 6). k, IFT20 immunoblot in Atg5−/− MEFs. n.s., statistically non-significant. Mean ± s.d. in d and j and mean ± s.e.m. in other panels.",
    "ncbi_link": "Atg5: 11793
IFT20: 55978"
  },
  {
    "caption": "E) Critically short telomeres arise after 90 population doublings in the absence of telomerase (tlc1). Genomic DNA was extracted at indicated population doublings and digested with XhoI. A radioactive probe was used to recognize telomeric DNA in a southern blot. Abbreviations: PD: population doubling.",
    "ncbi_link": "telomerase: 9164870
tlc1: 9164870"
  },
  {
    "caption": "F) tlc1 cells reach senescence at PD 80-100. %viability of indicated strains after propagation in YPD is indicated at different population doublings n=3. Asterisk indicates population doubling used in G) to determine binding of Npl3 to short telomeres by TAP-ChIP. 3 independent spores from the indicated genotypes were used. Population doublings are counted from germination of meiotic products and hence begin at approx. PD40. Abbreviations: TAP: tandem affinity purification tag",
    "ncbi_link": "tlc1: 9164870"
  },
  {
    "caption": "G) Npl3-TAP associates strongly to short telomeres. Cross-linked samples from indicated strains were used in a TAP-ChIP. Enrichment at telomeres was determined by quantitative PCR on indicated telomeres. Data represents mean % input +/- SEM n=3 (paired t-test one tailed *p<0.05, **p<0.01). PD90 refers to 90 population doublings in the absence of TLC1 (telomerase RNA subunit). The no tag control serves as an indicator of non-specific background signal. Abbreviations: TAP: tandem affinity purification tag, PD: population doubling.",
    "ncbi_link": "TLC1: 9164870
telomerase: 9164870"
  },
  {
    "caption": "A) Telomere interactors were identified and plotted as a volcano plot as in Figure 1 A, B and using tlc1 protein extracts. Interactors were identified using untreated protein extracts from tlc1 cells (left panel) or digested with RNase A and RNase H (right panel).",
    "ncbi_link": "tlc1: 9164870"
  },
  {
    "caption": "B) Npl3 associates to TERRA. Cross-linked samples from the indicated strains were subjected to Npl3-TAP RIP. Enrichment of the indicated RNAs was determined by quantitative PCR on pulled-down reverse-transcribed RNA. Data represents mean % input +/- SEM n=3 (unpaired t-test two tailed *p<0.05, **p<0.01).",
    "ncbi_link": "Npl3: 852042"
  },
  {
    "caption": "Npl3 associates strongly to telomeres in the absence of Rat1. C) The Rat1-AID tagged protein is strongly degraded following 1h of 1mM IAA treatment. Protein levels are determined using anti-FLAG (Rat1-AID) and anti-actin antibodies. Abbreviations: IAA: indole-3-acetic acid, AID: Auxin inducible degron.",
    "ncbi_link": "Rat1: 854213"
  },
  {
    "caption": "Npl3 associates strongly to telomeres in the absence of Rat1. D) TERRA levels increase in cells expressing the Rat1-AID variant after 1h treatment with 1mM IAA. TERRA levels were determined by quantitative PCR on reverse-transcribed RNAs after phenol-chloroform extraction. RNA levels are normalized to 7S ncRNA levels. Data represents fold increase to corresponding -IAA samples n=2. Abbreviations: IAA: indole-3-acetic acid, AID: Auxin inducible degron.",
    "ncbi_link": "Rat1: 854213"
  },
  {
    "caption": "Npl3 associates strongly to telomeres in the absence of Rat1. E) Npl3-TAP associates strongly to telomeres after 1mM IAA treatment in cells with Rat1-AID. Cross-linked samples from indicated strains were used in a TAP-ChIP. Enrichment at telomeres was determined by quantitative PCR on indicated telomeres. Data represents mean % input +/- SEM n=3 (paired t-test one tailed *p<0.05, **p<0.01). Abbreviations: IAA: indole-3-acetic acid, AID: Auxin inducible degron.",
    "ncbi_link": "Rat1: 854213"
  },
  {
    "caption": "F-G) Npl3 associates to telomeres in an R-loop dependent manner. E) RNH1 was overexpressed from a galactose-inducible promoter. Protein levels are determined using anti-HA and anti-actin antibodies. F) Npl3-TAP associates to telomeres in an R-loop-dependent manner. Cross-linked samples from indicated strains were used in a TAP-ChIP. Enrichment at telomeres was determined by quantitative PCR on indicated telomeres. Data represents mean % input +/- SEM n=3 (paired t-test one tailed *p<0.05, **p<0.01). Abbreviations: eV: empty vector control, oE: overexpression",
    "ncbi_link": "RNH1: 855274"
  },
  {
    "caption": "C) NPL3 over expression stabilizes telomeric R-loops. The indicated strains were grown on 1% raffinose 2% galactose to induce NPL3 over expression. Cross-linked samples were subjected to DRIP. DNA-RNA hybrids were immunoprecipitated using the S9.6 antibody. R-loop levels were determined by quantitative PCR on indicated telomeres. Data represents mean % input +/- SEM relative to 250 mM HU eV n=3 (paired t-test two tailed *p<0.05, **p<0.01). Abbreviations eV: empty vector control, oE: over expression HU: hydroxyurea. *p<0.05, **p<0.01",
    "ncbi_link": "NPL3: 852042"
  },
  {
    "caption": "D) Deletion of NPL3 decreases telomeric R-loops. The indicated strains were crosslinked and subjected to DRIP. DNA-RNA hybrids were immunoprecipitated using the S9.6 antibody. R-loop levels were determined by quantitative PCR on indicated telomeres. Data represents mean % input +/- SEM n=3. Specificity of S9.6 antibody was determined treating a fraction of the samples with RNase H.",
    "ncbi_link": "NPL3: 852042"
  },
  {
    "caption": "E-G) NPL3 stabilizes R-loops. E) R-loop dot blot. The indicated strains were grown on 1% raffinose 2% galactose for 72h and subsequently released into 1% raffinose 2% galactose or 2% glucose medium for 6 PDs. R-loop levels and dsDNA levels were determined using the S9.6 antibody and anti-dsDNA antibodies. Specificity of the S9.6 antibody was confirmed by treatment with RNase H. Loaded genomic DNA content is indicated at the bottom of the figure. F) R-loop dot blot quantification. Data represents R-loop signal as the S9.6 antibody signal relative to corresponding dsDNA signal n=3 (unpaired t-test two tailed *p<0.05). G) Serial dilutions of indicated strains were assayed on 1% raffinose 2% galactose media. Plates were imaged after 72h incubation at indicated temperatures. Abbreviations: V: empty vector control, oE: over expression, ds: double-strand,",
    "ncbi_link": "NPL3: 852042"
  },
  {
    "caption": "Quantification of the number of  quaternary branches  (indicated in schematic) in different  aman-2  alleles and in wild type control animals. All loss of function alleles of aman-2  display a significant decrease in PVD quaternary branch number. Data are represented as mean ± SEM. Statistical significance was calculated using the Kruskal-Wallis test and is indicated (****p ≤ 0.0001). n = 15 for all genotypes and are biological replicates.",
    "ncbi_link": "aman-2: 179632"
  },
  {
    "caption": "Fluorescent images and tracings of PVD  in mnr-1(dz213) hypomorphic animals alone and in combination with an aman-2(gk248486) null mutant. The dz213  introduces a L135F missense mutation in the DUF2181 domain of MNR-1/Menorin. PVD  is visualized by the dzIs53  transgene. The cell body is marked with an asterisk. Scale bars represent 20μm. Quantification of the number of full tertiaries  in genotypes indicated and traced in (F). The loss of aman-2 severely enhances the  mnr-1(dz213) phenotype. Control indicates wild type control animals as shown in (A). Data are represented as mean ± SEM. Statistical significance was calculated using the Mann-Whitney test and is indicated (****p ≤ 0.0001; ns= not significant). n >23 for all genotypes and are biological replicates.",
    "ncbi_link": "aman-2: 179632
mnr-1: 180350
Menorin: 180350
MNR-1: 180350"
  },
  {
    "caption": "Fluorescent images and tracings of PVD  in kpc-1(dz254) hypomorph animals alone and in combination with an aman-2(gk248486) null mutant. PVD  is visualized by the dzIs53  transgene. White arrows indicate self-avoidance defects in tertiary branches. Red arrows show gaps between tertiary branches (no self-avoidance defects). The cell body is marked with an asterisk. Scale bars represent 20μm. Quantification of the percent of self-avoidance defects in genotypes indicated and traced in (G). Control indicates wild type control animals as shown in (A). The loss of aman-2  suppresses defects in the kpc-1(dz254) phenotype. Data are represented as mean. Statistical significance was calculated using the Z-test and is indicated (****p ≤ 0.0001). n >15 for all genotypes and are biological replicates.",
    "ncbi_link": "aman-2: 179632
kpc-1: 173051"
  },
  {
    "caption": "Fluorescent images and tracings of wild type control (top) and lect-2(gk846764) hypomorphic animals (bottom) fed on plates with 300µm swainsonine  vs a DMSO  control. PVD  is visualized by the wyIs581 transgene. The  cell body  is denoted with an asterisk. Anterior is to the left and dorsal is up in all panels. Vesicular gut  autofluorescence is visible as white circular staining. Scale bars represent 20μm. Quantification of the number of full tertiaries in denoted genetic backgrounds (aman-2 null is gk248486). Black data points indicate DMSO  and orange data points show swainsonine treated animals. Data are represented as mean ± SEM. Statistical significance was calculated using the Mann-Whitney test and is indicated (****p ≤ 0.0001; ns= not significant). n = 12 for all genotypes and are biological replicates. Quantification of the number of quaternary dendrites in wild type control animals fed on plates with and without 300µm swainsonine. Animals treated with swainsonine  show a significant decrease in quaternary branch number, Data are represented as mean ± SEM. Statistical significance was calculated using the Mann-Whitney test and is indicated (****p ≤ 0.0001). n = 12 for each experiment and are biological replicates.",
    "ncbi_link": "aman-2: 179632
lect-2: 173978"
  },
  {
    "caption": "(B) Fluorescent composite images (top) and tracings (bottom) of mnr-1(dz213) in an aman-2(gk248486) and an aman-2(gk248486);  MGAT-1(null) background. An MGAT  null mutant lacks the three C. elegans paralogs: gly-12, gly-13, and gly-14. PVD  is visualized by the wyIs581 transgene. The  cell body is denoted with an asterisk. Anterior is to the left and dorsal is up in all panels. Scale bars represent 20μm. (C) Quantification of full tertiaries of denoted genotypes. Data are represented as mean ± SEM. Statistical comparisons were performed using the Kruskal-Wallis test. Statistical significance is indicated (***p ≤ 0.001, ****p ≤ 0.0001, ns=not significant). n=15 for all genotypes and are biological replicates. (D) Quantification of the number of quaternary branches in wild type control, aman-2(gk248486) null ,and MGAT1(null) animals. Loss of MGAT1  suppresses the decrease in quaternary branch  number in the aman-2(null) background. Data are represented as mean ± SEM. Statistical significance was calculated using the Kruskal-Wallis test and is indicated (**p ≤ 0.01, ****p ≤ 0.0001). n = 15 for all genotypes and are biological replicates.",
    "ncbi_link": "aman-2: 179632
gly-12: 181005
gly-13: 181160
gly-14: 175453
mnr-1: 180350"
  },
  {
    "caption": "Western blot against GFP  in C. elegans lysate expressing no transgenes (N2) and expressing DMA-1::GFP  (qyIs369), after precipitating with anti-GFP  antibody. The red boxed plus sign indicates that the lysate is treated with the PNGase F glycosidase. The downwards size shift reveals that N-glycan structures are present on DMA-1. Ladder is marked in kilodaltons (kDa). The GFP  tag contains no N-glycosylation sites. The experiment was repeated four times with biological replicates.",
    "ncbi_link": "GFP: 
DMA-1: 187968"
  },
  {
    "caption": "Western blot  against GFP  in C. elegans lysate  DMA-1::GFP  (qyIs369), after precipitating with anti-GFP  antibody. Control indicates an otherwise wild type background as opposed to an aman-2(gk248486) null background. The upward size shift in the mutant reveals that the loss of aman-2  alters the identity of N-glycan structures on DMA-1. The experiment was repeated four times with biological replicates.",
    "ncbi_link": "aman-2: 179632"
  },
  {
    "caption": "Western blot  against GFP  in C. elegans lysate DMA-1::GFP  (qyIs369), after precipitating with anti-GFP  antibody. Control indicates an otherwise wild type background as opposed to an aman-2(gk248486) null background. The red boxed +F indicates that the lysate is treated with the PNGase F glycosidase, while the green boxed +H corresponds to the Endo H glycosidase, which cleaves high-mannose  and hybrid type N-glycans. For complementary experiments using the Endo D glycosidase, which cleaves paucimannose  type N-glycans, Size shifts indicate that some hybrid/high-mannose  structures are present on DMA-1  (left), and that the  aman-2  mutant results in only hybrid/high-mannose  structures on DMA-1 (right). The experiment was repeated four times with biological replicates.",
    "ncbi_link": "aman-2: 179632"
  },
  {
    "caption": "Quantification of the number of quaternary branches in  DMA-1::2xFLAG control animals and animals with combinations of DMA-1::2xFLAG N-glycan  attachment sites mutated. Note that  DMA-1::2xFLAG control animals display a slightly reduced number of quaternary dendrites  compared to wild type animals Data are represented as mean ± SEM. Statistical significance was calculated using the Kruskal-Wallis test and Mann-Whitney between individual comparisons, and is indicated (**p ≤ 0.01, ****p ≤ 0.0001, ns=not significant). n = 15 for all genotypes and are biological replicates.",
    "ncbi_link": "FLAG: 
DMA-1: 187968"
  },
  {
    "caption": "Quantification of the number of  quaternary branches in  DMA-1::2xFLAG control animals alone and in combination with an aman-2(gk248486) null mutant (shaded in red). Control data is identical as in (B) and shown for comparison only. Data are represented as mean ± SEM. Statistical significance was calculated using the Kruskal-Wallis test and Mann-Whitney between individual comparisons, and is indicated (**p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001, ns=not significant). n = 15 for all genotypes and are biological replicates.",
    "ncbi_link": "FLAG: 
aman-2: 179632
DMA-1: 187968"
  },
  {
    "caption": "Fluorescent images (left) and tracings (center) of PVD  in animals of denoted backgrounds (aman-2(null) is gk248486). S4 corresponds to the endogenous alteration of  N-glycan attachment site N386 of  DMA-1. PVD  is visualized by the dzIs117 transgene. The cell body  is marked with an asterisk. Scale bars represent 20μm.",
    "ncbi_link": "aman-2: 179632
DMA-1: 187968"
  },
  {
    "caption": "G. Representative images of astrocytes labeled with Aldh1l1-EGFP reporter in cortex and OB of Daam2 cHet and cKO mice at postnatal day 28 (P28). Scale bar: 50 μm. H-K. Overall complexity of astrocytes with Aldh1l1-EGFP reporter was measured by Sholl analysis (Two-way ANOVA) and total process length (Student's t-test). Data is presented as mean ± SEM. n= 6-10 cells from N=3-5 mice per genotype, *p<0.05, p****<0.0001",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "A. Representative images of GFAP immunostaining in Daam2 cKO mice compared to controls in cortex and OB at P28. Scale bar: 20 μm.",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "D. Western blot analysis showed a significant increase in the amount of GFAP protein in Daam2 KO primary astrocytes. N=2",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "F. Overexpression of Daam2 via injection of AAV-GfaABC1D-myc-Daam2 in wild type P1 pups revealed reduced GFAP intensity compared to animals injected with control virus (AAV-GfaABC1D-GFP). AAV-GfaABC1D-myc-Daam2 was injected into Aldh1l1-GFP reporter mice for morphological complexity analysis and infected cells (Myc positive) were compared with non-infected cells. Dotted white line indicates virus-infected cells. Filled triangles and empty triangles indicate astrocytic primary branches with the control and reduced level of GFAP or Aldh1l1-GFP, respectively. Scale bar: 20 μm.",
    "ncbi_link": "GFP: 
myc: 
Aldh1l1: 107747
Daam2: 76441"
  },
  {
    "caption": "E. Schematics of astrocytic calcium imaging and representative images of spontaneous calcium signaling (green) of Daam2 cHet and cKO mice injected with AAV-GfaABC1D-GCaMP6f virus in OB. Approximate territory of astrocytes including soma and multiple microdomains is outlined in yellow. Representative traces of GCaMP6f signal in Daam2 cHet and cKO astrocytes are shown in black and red respectively. F-H. Quantification of amplitude (F), frequency (G), and area under curve (AUC) (H) of ∆F/F GCaMP6f signal events in OB. Amplitude and AUC of Daam2-deficient astrocytes are significantly increased in OB. Data is presented as mean ± SEM. Total number of cells is n=16, 15 (F-H) from N=3-4 mice of each genotype. Student's t-test was used for statistics, *p<0.05. ",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "A-F. (A, D) Schematics of whole cell recording in ex vivo brain slices and representative traces of spontaneous EPSC and IPSC in neurons in cortex from Daam2 cHet (top, black) and cKO (bottom, red) mice. (B-C, E-F) Quantification of amplitude and frequency of sEPSC and sIPSC in each genotype. Data is presented as mean ± SEM. Total number of cells is n=19, 20 (B-C) and 17, 13 (E-F) from N=7 mice for each genotype. Student's t-test was used for comparison, *p<0.05.",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "A. Astrocyte-specific Daam2 cKO mice show delays in buried food finding. N=13, 15 mice per genotype. Data is presented as mean ± SEM. Student's t-test was used, *p<0.05.",
    "ncbi_link": "Daam2: 76441"
  },
  {
    "caption": "F-J. Representative images of GFAP immunostaining (F) and quantification (G-J) in controls, Daam2 icKO, Slc4a4 icKO, and double icKO 6 weeks after tamoxifen injection. Scale bar: 20 μm. Data is presented as mean ± SEM. n=10-24 images, N=3-4 mice per genotype. Scale bar: 20 μm. Two-way ANOVA is used for statistics. [*] and [#] indicates comparison with control and double icKO, respectively. **p<0.01, p***<0.001, ##p<0.01.",
    "ncbi_link": "Daam2: 76441
Slc4a4: 54403"
  },
  {
    "caption": "RT‐PCR performed on cDNA from RNA isolated from splenic B cells derived from Tam‐treated mb1‐CreERT2 (left lane) or mb1‐CreERT2;Sykfl/flmice (right lane); the Syk‐ and Hprt‐specific amplification products were identified by agarose gel electrophoresis with Hprt used as an endogenous loading control.",
    "ncbi_link": "Cre: 
Hprt: 
ER: 13983///13982
Syk: 20963"
  },
  {
    "caption": "Immunoblot analysis of proteins isolated from B cells derived from spleens of mb1‐CreERT2 (left lane) or mb1‐CreERT2;Sykfl/fl (right lane) mice both treated with Tam as described; blots were probed with anti‐Syk and anti‐GAPDH Ab, GAPDH being used as a loading control.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "Intracellular flow cytometric analysis for Syk expression in B cells derived from the LN of Syk‐deficient and control mice.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "Genomic DNA analysis of Tam‐treated mb1‐CreERT2 or mb1‐CreERT2;Sykfl/flmice (as indicated). Upper row: amplification of floxed (fl) and wt (+) alleles. Middle row: amplification of the deleted (d) allele. Lower row: loading control (TC21, a gene unaffected by the deletion of Syk). Established control DNA was used to visualize the individual bands (as indicated).",
    "ncbi_link": "TC21: 
Syk: 20963"
  },
  {
    "caption": "A, B Flow cytometric analysis of B cells from (A) the BM and (B) the SP of mb1‐CreERT2 control (left) and mb1‐CreERT2;Sykfl/flmice (right) treated with Tam as described in the Materials and Methods section. The BM cells were stained with anti‐IgM and anti‐B220, and the SP cells with anti‐CD19 and anti‐CD93 or anti‐CD23 and anti‐CD21. The gated regions in the dot blots correspond to individual B‐cell populations: (A) Bone marrow: gate P (B220+IgM−) pro‐/pre‐B cells, gate I (B220loIgM+) immature B cells, gate M (B220hiIgM+) mature B cells; (B) spleen: gate T (CD19+ CD93+) transitional B cells (T), gate M (CD19+ CD93−) mature B cells; in CD93−splenic B cells, gate M (CD23hiCD21int CD93−) mature follicular B cells and gate MZ (CD23lo CD21hi CD93−) marginal zone B cells. The numbers in the dot plots indicate the mean relative frequency of cells in the gate.C-E Statistical analysis of absolute cell numbers per Tam‐treated mouse: filled circles indicating cells obtained from mb1‐CreERT2 control mice and open circles from mb1‐CreERT2;Sykfl/flmice. (C) Statistical analysis of the absolute cell numbers of pro‐/pre‐, immature and mature recirculating B cells in the BM. (D) Absolute cell numbers of transitional, M and MZ B cells found in the SP. (E) Statistical analysis of the absolute cells numbers of peritoneal B cell subsets B1‐a and B1‐b. An asterisk (*) marks statistically significant differences (P 0.05), two asterisks (**) indicate P 0.01, P‐values were obtained using two‐tailed Student's t‐test. Cell numbers of four to five mice per group are shown, with each dot representing an individual animal.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "A Flow cytometric analysis of IgM, CD19 and CD23 expression of splenic B cells from Tam‐treated mb1‐CreERT2 control (dashed line) and mb1‐CreERT2;Sykfl/flmice (solid line).",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "B Flow cytometric analysis of tyrosine phosphorylation (pY) in splenic B cells from Tam‐treated mb1‐CreERT2 and mb1‐CreERT2;Sykfl/flmice stimulated with medium (dotted line) or 50 μM pervanadate (dashed and solid lines).",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "C, D Flow cytometric analysis of the intracellular Ca2+ influx in purified splenic B cells derived from Tam‐treated mice. mb1‐CreERT2 or mb1‐CreERT2;Sykfl/fl were treated with (C) 10 μg/ml anti‐Kappa F(ab′)2 fragments or (D) 1 μM ionomycin.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "Ex vivo activation assay of splenic mature B cells from Tam‐treated mb1‐CreERT2 (upper row) or Tam‐treated mb1‐CreERT2;Sykfl/flmice (lower row). Purified splenic B cells were either left unstimulated (medium) or were stimulated with the indicated stimuli. The cells were analyzed by flow cytometry after 24 h. Shown are CD19 versus CD86 dot plots. 7‐AAD was included to distinguish dead from viable cells. The numbers in the quadrants indicate the relative frequencies of cells in the gate.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "Ex vivo proliferation assay with mature B cells from Tam‐treated mb1‐CreERT2 (upper row) or Tam‐treated mb1‐CreERT2;Sykfl/flmice (lower row). The cells were incubated with the indicated stimuli for 90 h.",
    "ncbi_link": "Syk: 20963"
  },
  {
    "caption": "A Flow cytometric analysis of splenic B cells from Rag2−/−;γc−/− mice. CD19 versus CD3ε dot plots are shown. The mice were injected i.v. with 5 × 106 splenic (CD19+ CD93−) B cells and (CD3ε+) T cells from Tam‐untreated mb1‐CreERT2 control or mb1‐CreERT2;Sykfl/fl mice. The recipient mice were treated with Tam beginning 1 day after transfer as described in the Materials and Methods section.B Quantitative analysis of B and T cells from Rag2−/−;γc−/− mice repopulated with mb1‐CreERT2 or mb1‐CreERT2;Sykfl/fl splenocytes. Each symbol represents an individual mouse. Filled circles and squares represent Syk+/+ B and T cells, respectively; open circles and squares represent Sykfl/fl B and T cells.",
    "ncbi_link": "Rag2: 
Syk: 20963"
  },
  {
    "caption": "(E) Representative western blot  of scr or miR-30c transfected  TREx  cells analysed for  ORF65 expression with  GAPDH as a loading control. Densitometry analysis performed on n=3. Data information: data are presented as mean ± SD. **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "miR-30c: 407031"
  },
  {
    "caption": "(F) Representative  western blot  of scr or  miR-29b transfected TREx cells analysed for ORF65 expression  with GAPDH as a loading control. Densitometry  analysis performed on n=3. Data information: data are presented as mean ± SD. **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "miR-29b: 407024"
  },
  {
    "caption": "(C) Representative  western blot of  ORF65 levels in scr and circHIPK3 KD cell lines with  GAPDH as a loading control. Densitometry  analysis of n=3 western blots. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "HIPK3: 10114"
  },
  {
    "caption": "(D) Representative  western blot of  DLL4 levels in scr and circHIPK3 stable TREx cells at 0 and 24 hours post induction with GAPDH as a loading control.  Densitometry analysis of n=3. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "HIPK3: 10114"
  },
  {
    "caption": "(F) Representative western blot  of DLL4 levels in scr or  miR-30c transfected  TREx  cells at 0, 24 and 48 hours post induction with  GAPDH as a loading control. Densitometry  analysis of n=3 Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "miR-30c: 407031"
  },
  {
    "caption": "(J) Representative western blot of DLL4 levels in scr or  miR-30c antagomiR transfected  TREx  cells at 0, 24 and 48 hours post induction with  GAPDH as a loading control. Densitometry analysis of n=3. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "miR-30c: 407031"
  },
  {
    "caption": "(B) Representative western blot  of DLL4 levels in scr and  DLL4 KD TREx  cells with GAPDH as a loading control,  densitometry analysis is n=3. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "DLL4: 54567"
  },
  {
    "caption": "(C) Representative western blot  of ORF65 levels at 0, 24 and 48 hours post induction in scr and DLL4 KD TREx  cells, GAPDH was used as a loading control and densitometry analysis performed on n=3. Data information: data are presented as mean ± SD. *P<0.05, **P<0.01, ***P<0.001 (Unpaired Student's t-test). All repeats are biological.",
    "ncbi_link": "DLL4: 54567"
  },
  {
    "caption": " Growth was tested in the presence of ceftriaxone at 8 µg/ml (+ ceftriaxone) or in the absence of the drug (- ceftriaxone) on BHI agar plates supplemented with 40 µM IPTG and 1% L-arabinose for induction of ycbB and relA', respectively. (A) BW25113 ΔrelA derivatives harboring plasmids pKT2(ycbB), pKT8(relA') and the vectors pHV6 and pHV7 used to construct these plasmids, respectively. Expression of β-lactam resistance requires induction of both ycbB and relA'.",
    "ncbi_link": "ycbB: 945541
relA: 947244"
  },
  {
    "caption": "  (B) BW25113(ycbB, relA') and its derivatives obtained by individual deletion of endopeptidase genes. BW25113(ycbB, relA') is an abbreviated name for BW25113 ΔrelA pKT2(ycbB) pKT8(relA').  ",
    "ncbi_link": "ycbB: 945541
relA: 947244"
  },
  {
    "caption": " Growth of BW25113(ycbB, relA'), BW25113(ycbB, relA') ΔmepM, and its derivatives harboring plasmids encoding MepM, MepM H393A, and MepM ΔLytM were tested in the presence of ceftriaxone at 8 µg/ml (+ ceftriaxone) or in the absence of the drug (- ceftriaxone) in BHI agar plates supplemented with 40 µM IPTG and 1% L-arabinose for induction of ycbB and relA', respectively. The genes encoding MepM, MepM H393A, and MepM ΔLytM were inserted into the vector pHV9 under the control of the PphlF promoter, which is inducible by 2,4-diacetylphloroglucinol (DAPG). Basal level of expression of mepM under the control of PphlF was sufficient to restore ceftriaxone resistance in the absence of the inducer.",
    "ncbi_link": "phlF: 
ycbB: 945541
mepM: 946376
MepM: 946376
relA: 947244"
  },
  {
    "caption": " The mepM gene was expressed under the control of TIS1 or TIS2 (translation initiation) and of PrhaBAD (the L-rhamnose-inducible promoter of vector pHV30). Growth of BW25113(ycbB, relA') ΔmepM harboring the pHV30 derivatives was tested on BHI agar supplemented with ceftriaxone 8 µg/ml, IPTG 40 µM (induction of ycbB) and L-arabinose 1% (induction of relA'). (A) For TIS2, growth around paper disks containing 1 or 2 mg of L-rhamnose indicated that induction of the expression of mepM was required for ceftriaxone resistance. In contrast, a higher level of translation from TIS1 was sufficient for ceftriaxone resistance in the absence of the inducer. (B) The experiment was repeated with bacteria pre-exposed to L-rhamnose that were harvested at the vicinity of the disk containing 2 mg of L-rhamnose. Expression of ceftriaxone resistance remained dependent on the presence of L-rhamnose indicating that the requirement for MepM is not transient. The diameter of the growth zones is larger in panel (B) than in panel (A) as expected from the fact that bacteria in the inoculum used in (B) had been grown in the presence of the inducer and already contained MepM. In (A) growth is only possible after diffusion of L-rhamnose in the medium prior to the action of ceftriaxone. At a distance from the disk, diffusion was not sufficiently rapid to observe resistance. ",
    "ncbi_link": "ycbB: 945541
MepM: 946376
mepM: 946376
relA: 947244
rhaBAD: 948401///948400///948399"
  },
  {
    "caption": " (A) rpHPLC chromatograms of sacculi isolated from BW25113 grown in minimal medium to stationary phase and digested by lysozyme (upper panel) or by lysozyme and 5 µM MepM (lower panel). Absorbance was monitored at 205 nm (mAU, milli-absorbance unit). ",
    "ncbi_link": "MepM: 946376"
  },
  {
    "caption": " Functional complementation of the mepM deletion in BW25113(ycbB, relA') ΔmepM was performed with the pHV30 vector or recombinant plasmids encoding each of the eight endopeptidases under the control of the PrhaBAD promoter and of the TIS1 translation initiation signal. Induction of endopeptidase (ED) genes was performed with 0.2% L-rhamnose in the presence or absence of 8 µg/ml ceftriaxone. BHI agar plates contained 40 µM IPTG and 1% L-arabinose for induction of ycbB and relA', respectively. ",
    "ncbi_link": "ycbB: 945541
mepM: 946376
relA: 947244
rhaBAD: 948401///948400///948399"
  },
  {
    "caption": " (B) The plating efficiency assay was performed with derivatives of BW25113 Δ8EDs pHV53(mepM) harboring the vector pHV7 or recombinant plasmids carrying each of the eight endopeptidase genes under the control of the ParaBAD promoter. In this assay, functional replacement of MepM is detected based on growth in media containing 0.2% or 1% L-arabinose for expression of the endopeptidase gene carried by vector pHV7, while by-passing the requirement for induction of the mepM copy of pHV53 by L-rhamnose. Complementation was observed with both concentrations of inducer for mepH, mepS, and pbpG. Overproduction of mepM encoded by the pHV7 derivative in the presence of the high dose of L-arabinose (1%) was lethal. The right panel presents the growth control performed in the presence of 0.2% L-rhamnose for induction of the mepM copy carried by pHV53. ",
    "ncbi_link": "araBAD: 
mepH: 945210
mepM: 946376
MepM: 946376
mepS: 946686
pbpG: 946662"
  },
  {
    "caption": " (B) Functional complementation of the mepK deletion of BW25113 ΔmepK pHV63(ycbB) was performed with the pHV30 vector or recombinant plasmids encoding each of the eight endopeptidases under the control of the PrhaBAD promoter. Induction of ycbB and of endopeptidase (ED) genes was performed with 0.2% L-arabinose and 1% L-rhamnose, respectively. BHI agar plates contained chloramphenicol (20 µg/ml) to counter-select loss of pHV63(ycbB). ",
    "ncbi_link": "ycbB: 945541
mepK: 945538
rhaBAD: 948401///948400///948399"
  },
  {
    "caption": " (A) Functional complementation of the mepK deletion of BW25113 ΔmepK pHV63(ycbB) was performed with the pHV30 vector or recombinant plasmids encoding mepA, mepK, mepS or derivatives encoding catalytically inactive endopeptidases under the control of the PrhaBAD promoter. (B) The complementation assay was repeated for BW25113 Δ7EDs pHV63(ycbB), which was obtained by deletion of all chromosomal endopeptidase genes except mepM. Induction of ycbB and of endopeptidase (ED) genes was performed with 0.2% L-arabinose and 1% L-rhamnose, respectively. BHI agar plates contained chloramphenicol (20 µg/ml) to counter-select loss of pHV63(ycbB). ",
    "ncbi_link": "ycbB: 945541
mepA: 946812
mepK: 945538
mepM: 946376
mepS: 946686
rhaBAD: 948401///948400///948399"
  },
  {
    "caption": " (A) Growth curves of (i) BW25113(ycbB, relA') and its ΔsltY derivative; and (ii) strain M1 and its derivatives (M1.1 to 1.4) harboring mutations in sltY. The growth medium contained (i) 40 µM IPTG, 1% L-arabinose, and 8 µg/ml ceftriaxone for BW25113(ycbB, relA') and its ΔsltY derivative or (ii) 50 µM IPTG and 16 µg/ml ampicillin for M1 and its derivatives. ",
    "ncbi_link": "ycbB: 945541
relA: 947244
sltY: 948908"
  },
  {
    "caption": " C, Dose-response curves of BEAS-2B and BEAS-2B-KRAS cells treated for 72 hours with inhibitors of FGFR (AZD4547, BGJ398) and PLK1 (BI2536, BI6727), alone or combination. Values of Fa and CI are shown underneath, with CI<1.0 indicating synergistic effect. Data were from three independent experiments (n=3), error bar: SD ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " D, BEAS-2B and BEAS-2B-KRAS treated with the indicated drugs, alone or combination for 72 hours, were cultured in drug-free medium for additional 7-21 days. Surviving cells after the treatment were fixed and visualized by crystal violet staining. ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " C, Clongenic assay of KRAS-mutant lung and pancreatic cells (MIA PaCa-2, H2122, H2009, H23, H358 and A549) treated with control (DMSO), AZD4547 (5 µM) and BI2536 (5 nM), alone or combination. ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " D, Apoptotic assay of KRAS-mutant cancer cells (H358, H441, A549, and SW620) and KRAS-WT lung cancer cells (EBC-1) treated with vehicle (DMSO), AZD4547 (5 µM) and BI2536 (5 nM), alone or in combination for 48h. Data are presented as mean ± SD (n=3). ***P<0.001 and ****P<0.0001 by two-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " E, KRAS mutant lung (A549, H358，H441), pancreatic (MIAPaCa-2) and colon (SW620) cancer cells were transfected with control siRNAs, FGFR1- and PLK1-specific siRNAs, alone or combination. Cell viability was determined 72 h post transfection. Data are presented as mean ± SD (n=3). **p<0.01, ****p<0.0001, and ns P＞0.05 by two-way ANOVA with Tukey's multiple comparisons test. ns, no significance. ",
    "ncbi_link": "FGFR1: 2260
KRAS: 3845
PLK1: 5347"
  },
  {
    "caption": " D, E, Immunoblots (D) and viability assay (E) of H358 and A549 cells transfected with E2F1-specific or control siRNAs followed by treatment (48 h post transfection) with vehicle (DMSO) or combined AZD 4547 (5 µM)/BI2536(5 nM) for additional 24 hours. Data were shown as mean ± SD (n=3). **P<0.01, ****P<0.0001 and P＞0.05 (ns) by two-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "E2F1: 1869"
  },
  {
    "caption": " F, H358 cells transfected with E2F1-specific or control siRNAs for 24h were subsequently treated with vehicle (DMSO), AZD4547 (5 µM) and BI2536 (5 nM), alone or combination for 48h before apoptotic assay. Data were shown as mean ± SD (n=3). *P<0.05, **P<0.01 and P＞0.05 (ns) by two-way ANOVA with Tukey's multiple comparisons test. ",
    "ncbi_link": "E2F1: 1869"
  },
  {
    "caption": " F, Immunoblots of H358 cells transfected with ATG5-specific or control siRNAs for 48h and before treated for 24h with vehicle (DMSO) or combined AZD 4547 (5 µM)/BI2536 (5 nM). ",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": " A, Growth curve of a KRAS-mutant lung cancer PDX (BE564T) treated with vehicle, HCQ (30 mg/kg/day), AZD4547 (10 mg/kg/day) and BI6727 (5 mg/kg/day), alone or in combination. *P<0.05, ***P<0.001 and P＞0.05 (ns) by one-way ANOVA with Tukey's multiple comparisons test. Data are the mean of tumor volume of each group (5 mice/group); error bar: SD ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " F-K, Growth curves (F, I) of KRAS-mutant lung cancer PDXs (PF139, PF563) treated with vehicle, HCQ (30 mg/kg/day), AZD4547 (10 mg/kg/day) and BI6727 (5 mg/kg/day), alone or in combination. *P<0.05, **P<0.01, ***P<0.001 by one-way ANOVA with Tukey's multiple comparisons test. Data are the mean of tumor volume of each group (4 mice/group); error bar: SD Relative tumor volume (G, J) and weights (H, K) of the PDX tumors after the treatment. *P<0.05, **P<0.01, ***P<0.001 and P＞0.05 (ns) by unpaired two-tailed t-test. Data are the mean ± SD (error bar) of tumor weights of each group (4 mice/group). ",
    "ncbi_link": "KRAS: 3845"
  },
  {
    "caption": " F, Box plots showing the percentage of Ki67-positive cells in different treatment groups. Data are based on IHC staining of lung tissue section of LSL-KrasG12D mice. *P<0.05 and P＞0.05 (ns) by two-way ANOVA with Tukey's multiple comparisons test. The boxplots span from the first to third quartile, the whiskers extend to 1.5× the interquartile range (IQR). The horzontal line within the boxes represents the median of each group of 10 replicates (n=10). ",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "C-F (C, E) Immunofluorescence labelling with an antibody that recognizes both full-length and cleaved Xkr8 in developing (P0, P8) and adult S1 cortex and hippocampus. (D, F) Immunofluorescence labelling with an antibody recognizing full-length uncleaved Xkr8 in developing (P0, P8) and adult S1 cortex and hippocampus. Loss of Xkr8 immunosignal in double transgenic Xkr8flx/flx;Emx1::Cre animals (Xkr8 cKO) is observed with both Xkr8 antibodies (C-F).",
    "ncbi_link": "Cre: 2777477
Emx1: 13796
Xkr8: 381560"
  },
  {
    "caption": "A, B Organotypic slices of Xkr8 WT and cKO hippocampus with Thy1::GFP neurons (green) were labelled with PtdSer-binding fluorescently tagged Annexin V (magenta) at 16-19 DIV. The fluorescence of bound Annexin V was quantified on ImageJ by measuring the integrated density of fluorescent structures within the same volume for each slice and expressing the value as fluorescence units (f.u.; two-tailed Student's t-test, each dot represents an individual slice preparation, n = 4).",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "C Immunofluorescence labelling of active caspase-3 in developing brain from P8 to P28 in Xkr8 WT and Xkr8 cKO brains was quantified and compared by nested design and mixed model ANOVA (F(2,30) = 0.86, p = 0.433), each dot represents an individual mouse (n = 6 per age group)",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "A-C The size and density of axonal boutons on Thy1::GFP axons (green) in Xkr8 WT and cKO animals (nested design and mixed model ANOVA, each dot represents an individual mouse, n = 6 per age and genotype group).",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "D, E Dendritic spine morphology (D) and density (E) of Thy1::GFP+ CA1 neurons in Xkr8 WT and cKO animals from P8 to P28 (nested design and mixed model ANOVA, each dot represents an individual mouse, n = 5-6 per age and genotype group).",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "J-L The density of cortical (vGluT1+, J) and thalamic (vGluT2+, K) and the ratio of vGluT1+ and vGluT2+ inputs (L) in Xkr8 WT and cKO brains (nested design and mixed model ANOVA, each dot represents an individual mouse, n = 6 per age and genotype group).",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "A-F The immunolabelling of internalized pan-axonal material (A, B), pre-synaptic vGluT1 particles (C, D) and post-synaptic PSD95 particles (E, F) within Iba1+ microglia in P8 cortex of Xkr8 WT and Xkr8 cKO mice was quantified per individual 3D reconstructed microglial cell. The total volume of internalized particles was normalized to microglial cell volume and compared by nested design and mixed model ANOVA, each dot represents an individual mouse (n = 3 per genotype group). Data presented as mean ± SEM; ** p < 0.01, **** p < 0.0001; scale bar 10 µm, grid cell 10 µm.",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "A, B Corticospinal axons of the axonal bundles of pyramidal tracts in medulla of P8 and P28 Xkr8 WT and cKO mice were visualized by Palmgren staining and quantified per each bundle, delineated by a dashed line (Mann-Whitney test, n = 6 mice per genotype, the data are presented as median and quartiles).",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "To label callosal projections in vivo, cholera toxin subunit B (CTB) was injected stereotactically into corpus callosum of Xkr8 WT and cKO brains at P30-32. Back-labelled neurons were quantified in L4 of primary (S1) and secondary (S2) somatosensory cortex.",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "Xkr8 cKO neurons had increased mean sEPSC amplitude Data were analyzed by two-tailed Student's t-test ; n = 7-14 neurons per genotype.",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "F-H Evoked excitatory postsynaptic currents (eEPSC) of Xkr8 cKO neurons showed a trend to decrease (p = 0.08) (F, G) and the ratio of eEPSC and sEPSC amplitudes was lower in Xkr8 knockout neurons (H). two-way repeated measures ANOVA (H); n = 7-14 neurons per genotype.",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "A Brain regions with significantly increased functional connectivity in Xkr8 cKO mice compared to Xkr8 WT mice as identified by seed-based mapping of rsfMRI networks (t-test, p < 0.05 FWE cluster-corrected, with cluster-defining threshold of t24 > 2.07, p < 0.05; Colored regions represent the areas of the brain exhibiting increased functional connectivity in Xkr8 cKO compared to Xkr8 WT brains; color scale represents the level of functional correlation; abbreviations specify anatomical designations of identified regions. ACA: anterior cingulate cortex, AI: agranular insular area, AUD: auditory areas MOp: primary motor area, MOs: secondary motor area, PL: prelimbic area, SSp: primary somatosensory area, STR: striatum, STRd: striatum dorsal region, SUB: subiculum, TH: thalamus, VIS: visual areas, VISC: visceral area.",
    "ncbi_link": "Xkr8: 381560"
  },
  {
    "caption": "Autophagy is activated in dying nurse cells during late oogenesis in D. melanogaster. (A-C) Confocal micrographs of egg chambers of flies expressing the UASp-GFP-mCherry-DrAtg8a transgene exclusively in the germline (genotype: UASp-GFP-mCherry-DrAtg8a/+; nanos-VP-16 Gal4/+). Expression of UASp-GFP-mCherry-DrAtg8a exhibits punctate staining pattern (arrows). Note that during developmental stages early 12 (A) and late 12 (B), the punctate dots are yellow (merge). In late stage 13 (C), large red dots are evident, indicating the presence of acidic compartments (autolysosomes; arrows). The arrowheads in A point to the physical connection between the oocyte and the nurse cells during early stage 12 (not observed during late stage 12).",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(F) Nurse cell of a late stage 13 egg chamber expressing UASp-mCherry-DrAtg8a exclusively in the germline (genotype: UASp-mCherry-DrAtg8a/+; nanos-VP-16 Gal4/+). mCherry-DrAtg8a puncta are attached to or located adjacent to the fragmented nucleus (arrows and insets). Hoechst staining (blue) was performed to visualize the nuclei. Nurse cells are outlined with a white line. FC, follicle cell; FCN, follicle cell nucleus; OC, oocyte. Bars: (A-C) 10 µm; (D-F) 1 µm.",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "Genetic inhibition of autophagy in the germline prevents DNA fragmentation. Confocal micrographs of stage 13/14 egg chambers after TUNEL staining. (A) Wild-type (wt) stage 13 egg chamber contains nurse cell nuclei exhibiting fragmented DNA (positive TUNEL staining; arrows). (B) Wild-type stage 14 egg chambers do not contain nurse cells. Arrows point to the respiratory appendages (RA). (C-E) Stage 14 atg1−/− (C), atg13−/− (D), and vps34−/− (E) germline mutant chambers have persisting nurse cell nuclei that do not contain fragmented DNA (negative TUNEL staining; arrows). Nurse cells are outlined with a white line. Draq5/Hoechst staining (blue) was performed to visualize the nuclei. PhC, phase contrast. Bars, 50 µm.",
    "ncbi_link": "atg1: 39454
atg13: 40998
vps34: 37733"
  },
  {
    "caption": "Germline autophagy mutant egg chambers exhibit reduced expression of cleaved caspase-3. Confocal micrographs of stage 13/14 egg chambers stained for cleaved caspase-3(casp-3). (A) Wild-type (wt) late stage 13 egg chamber showing cleaved caspase-3 staining in the degenerating nurse cell cluster. (B) In wild-type stage 14 egg chamber, nurse cells are completely degraded (arrows). (C-E) atg1−/− (C), atg13−/− (D), and vps34−/− (E) germline mutant stage 14 egg chambers exhibit significantly reduced staining for cleaved caspase-3 and contain persisting nurse cell nuclei. Nurse cells are outlined with a white line. Draq5/Hoechst staining (blue) was performed to visualize the nuclei. PhC, phase contrast. (F) Quantification of mean intensity of cleaved caspase-3 staining observed in the nurse cells of stage 12-14 egg chambers in wild-type and germline autophagy mutant egg chambers. Wild type (WT): three independent experiments, n = 30 egg chambers; atg1−/− GLCs: four independent experiments, n = 30 egg chambers; atg13−/− GLCs: four independent experiments, n = 30 egg chambers; vps34−/− GLCs: three independent experiments, n = 30 egg chambers. Data are presented as mean ± SD. Difference was significant with P < 0.001 for all values versus wild type. Bars, 20 µm.",
    "ncbi_link": "atg1: 39454
atg13: 40998
vps34: 37733"
  },
  {
    "caption": "dBruce colocalizes with the autophagic marker Atg8a-GFP in the nurse cells during late oogenesis and is accumulated in autophagy germline mutants. Confocal micrographs of late stage egg chambers expressing Atg8a-GFP and stained for dBruce. (A-C) Stage 10 (A), early stage 12 (B), and late stage 12 (C). dBruce colocalizes with Atg8a-GFP in punctuate structures during stages 12 and 13 (insets in B and insets and arrows in C) and not during stage 10 (insets in A).",
    "ncbi_link": "Atg8a: 32001"
  },
  {
    "caption": "(D-G) Confocal micrographs of stage 14 wild-type (D) and autophagy mutant egg chambers (E-G) stained for dBruce. dBruce is accumulated in atg1, atg13, and vps34 mutant nurse cells (arrows). Draq5/Hoechst staining (blue) was performed to visualize the nuclei. Nurse cells are outlined with a white line. OC, oocyte; PhC, phase contrast. Bars, 10 µm.",
    "ncbi_link": "atg1: 39454
atg13: 40998
vps34: 37733"
  },
  {
    "caption": "dBruce is required for nurse cell survival by controlling DNA fragmentation during oogenesis. (A) Confocal micrographs of dBrucee00984 mutant ovarioles stained for TUNEL and DNA. Arrows point to degenerating stage 8/9 egg chambers that are TUNEL positive.",
    "ncbi_link": "Bruce: 41260
dBruce: 41260"
  },
  {
    "caption": "(B and C) Confocal micrographs of vps34/dBruceE81 and atg, dBruceE81 double mutant egg chambers stained for TUNEL (green and red, respectively) and DNA. (B) vps34−/−GLCs; dBruceE81/dBruceE81 stage 14 mutant egg chamber contain persisting TUNEL-positive nurse cell nuclei (outlined; arrow). (C) atg1−/−GLCs, dBruceE81/dBruceE81 stage 14 mutant egg chamber contain persisting TUNEL-positive nurse cell nuclei. atg1 mutant nurse cells are identified by the lack of GFP staining (outlined; arrow). Draq5/Hoechst staining (blue) was performed to visualize the nuclei. PhC, phase contrast. Bars, 50 µm.",
    "ncbi_link": "atg1: 39454
dBruce: 41260
vps34: 37733"
  },
  {
    "caption": "(C) Acoustic startle reflex test to compare hearing ability between Wt (N = 7) and Hpn-/- (N = 4) mice.",
    "ncbi_link": "Hpn: 15451"
  },
  {
    "caption": "(F) Immunoblot  analysis of phospho-Smad2/3 (TGFβ  pathway signaling marker) and total Smad2/3 in lysates from indicated tissues isolated from Wt, Hpn+/- and Hpn-/- mice. GAPDH  was used as the loading control. The histogram depicts quantification of pSmad2/3 compared to Wt normalized to total Smad2/3.",
    "ncbi_link": "Hpn: 15451"
  },
  {
    "caption": "(B) Immunoblot analysis of Wap-Myc mammary tumor lysates for the indicated TGFβ signaling markers and hepsin (T# denotes individual tumors). GAPDH was used as the loading control. Lysates were derived from Wap-Myc mammary tumors from 6 mice with and 6 mice without DOX-induced hepsin overexpression",
    "ncbi_link": "Myc: 
hepsin: 15451
Wap: 22373"
  },
  {
    "caption": "(D) Immunoblot analysis of phospho-Smad2/3, total Smad2/3, and GAPDH (loading control) expression in Wt tumors transplanted into either Wt or Hpn-/- recipients (n = 10 tumors each).",
    "ncbi_link": "Hpn: 15451"
  },
  {
    "caption": "(E) Western blot analysis of phospho-Smad2/3, total Smad2/3, hepsin, and β-tubulin (loading control) in MCF10A-pIND20-HPN cells treated with doxycycline (DOX; overexpression of hepsin) and the TGFβR1 inhibitor Galunisertib (TGFβR1i, 10µM) as indicated.",
    "ncbi_link": "hepsin: 3249
HPN: 3249"
  },
  {
    "caption": "(G) TGFβ ELISA assay to detect active and total TGFβ levels in conditioned medium from MCF10A-pIND20-HPN pL6-TGFβ1 cells with (DOX+) or without (DOX-) hepsin overexpressing. The TGFβ ELISA assay detects active TGFβ levels (first 2 columns), but heat treatment of the conditioned medium activates all TGFβ, thus effectively measuring total TGFβ (right two columns).",
    "ncbi_link": "hepsin: 3249
HPN: 3249
TGFβ1: 7040"
  },
  {
    "caption": "(A) Coomassie-stained protein gels with cell lysates and concentrated culture supernatants of MCF10A-pIND20-HPN cells, with (+DOX) or without (-DOX) hepsin overexpression. M indicates the media only control. R and NR above the gels indicate reducing and non-reducing conditions, respectively. Numbered arrowheads indicate areas of the gel that were analyzed by mass spectrometry; corresponding proteins differently expressed in hepsin overexpressing cells are listed on the left. The image with two lanes on the right is a copy of the indicated area with supernatant under reducing conditions, highlighting the part from which fibronectin was identified. Red boxes indicate the lanes that were analyzed by mass specrtometry",
    "ncbi_link": "hepsin: 3249
HPN: 3249"
  },
  {
    "caption": "(C) Immunoblot analysis of fibronectin, hepsin, and β-tubulin (loading control) in cell lysates from MCF10A-pIND20-HPN cells with (DOX+) or without (DOX-) hepsin overexpression. The graph shows the quantification of fibronectin levels.",
    "ncbi_link": "hepsin: 3249
HPN: 3249"
  },
  {
    "caption": "(A) Immunoblot analysis of fibronectin in indicated tissues isolated from Wt, Hpn+/- and Hpn-/- mouse (representative of at least three repeats). GAPDH blot is used here as the loading control.",
    "ncbi_link": "Hpn: 15451"
  },
  {
    "caption": "(C) Immunoblot analysis of fibronectin, hepsin, and β-tubulin (loading control) in prostate lysates of control mice or mice with prostate-specific hepsin overexpression N=2 mice each, the two prostate lobes were run separately (a and b).",
    "ncbi_link": "hepsin: 15451"
  },
  {
    "caption": "(A) Immunoblot analysis of fibronectin, pSmad2/3, total Smad2/3, and GAPDH (loading control) in cell lysates from MCF10A-pIND20-HPN cells without hepsin overexpression. The graph depicts quantification of pSmad2/3 normalized to total Smad2/3 levels, compared to siCtrl (N = 3 biological repeats). (B) Immunoblot analysis of cell lysates (pSmad2/3, total Smad2/3 and vinculin as loading control) and concentrated cell culture supernatant (anti-V5 for TGFβ) from MCF10A-pIND20-HPN pL6-TGFβ1-V5 cells without hepsin overexpression. Ponceau staining is shown as a loading control for the western blot with concentrated culture supernatant. The graph depicts quantification of pSmad2/3 normalized to total Smad2/3 levels, compared to siCtrl (N = 3 biological repeats).",
    "ncbi_link": "V5: 
hepsin: 3249
HPN: 3249
TGFβ1: 7040"
  },
  {
    "caption": "(E) Immunoblot analysis of fibronectin, pSmad2/3, total Smad2/3, hepsin, and GAPDH (loading control) in cell lysates from MCF10A-pIND20-HPN cells with (DOX+) and without (DOX-) hepsin overexpression, and with or without fibronectin silencing (siFN1). The graph depicts quantification of pSmad2/3 normalized to total Smad2/3 levels (N = 3 biological repeats).",
    "ncbi_link": "fibronectin: 2335
FN1: 2335
hepsin: 3249
HPN: 3249"
  },
  {
    "caption": " An S. typhimurium strain devoid of its SPI-1 TTSS effector proteins is able to induce programmed cell death in macrophages. BMDPM from wild-type (A) or caspase-1−/− (B) mice (Kuida et al., 1995) were infected with wild-type S. typhimurium or mutant derivative either lacking all TTSS effector proteins (effectorless) or defective for TTSS secretion by virtue a having a mutation on an essential component of this system (invG). 6 h after infection, cytotoxicity was evaluated by lactate dehydrogenase release or by terminal deoxynucleatide transferase (TUNEL) staining. Values for the lactate dehydrogenase release represent the average of at least three independent measurements. Equivalent results were obtained in several repetitions of these experiments. ",
    "ncbi_link": "SPI-1: 
TTSS: 
caspase-1: 12362
invG: 1254421"
  },
  {
    "caption": " Transient expression of SipB in BMDPM from caspase-1−/−mice results in cell death. Plasmids expressing either SipB, SipC, or SipD fused to YFP were introduced into BMDPM from caspase-1−/− mice as indicated in the Materials and methods section. Macrophages were then fixed, stained with DAPI (to visualize chromatin), and observed under a fluorescence microscope. Cells expressing SipC or SipD do not show any signs of cytotoxicity. In contrast, cells expressing SipB show clear signs of cytotoxicity and chromatin condensation. Arrows indicate the nucleus of transfected cells. ",
    "ncbi_link": "caspase-1: 12362
SipB: 1254408
SipC: 1254407
SipD: 1254406"
  },
  {
    "caption": "Transient expression of SipB in COS-2 cells. (A) A plasmid expressing YFP-tagged SipB was transfected into COS-2 cells, and its localization was examined under a confocal microscope.",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " (B) SipB colocalized with mitochondrial markers in transfected cells. COS-2 cells were transfected with a plasmid encoding either SipB-CFP (top) or SipB-YFP (bottom). Transfected cells were stained with MitoTracker® Red (Molecular Probes, Inc.) to visualize mitochondria and were examined by confocal microscopy. The SipB-induced structures were readily stained with mitochondrial markers (top). Mitochondria were also seen contained within the SipB-induced structures (bottom). ",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " (C) SipB-induced structures were labeled with the ER marker Sec-61. COS-2 cells were cotransfected with plasmids encoding SipB-YFP and Sec61-CFP, and transfected cells were examined by confocal microscopy. ",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " Immuno-EM of SipB-transfected COS-2 cells. COS-2 cells were transfected with a plasmid expressing SipB-YFP, and 24 h after transfection, cells were fixed and prepared for immuno-EM using an antibody specific for GFP and a gold-labeled anti-rabbit antibody. SipB was seen localized to structures made up of closely apposed membranes that were often in close proximity to mitochondria (A). Mitochondria were often seen apparently fusing to the SipB-induced membranous structure (B, see arrows in inset on top; C, inset to the right). Mitochondria were often seen contained with the SipB-induced membrane structures (D). Bars, 250 nm. ",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " The nonfusogenic SipB428-593 mutant localizes to the mitochondria, but does not form multivesicular structures and interferes with the activity of the wild-type protein. (A) COS-2 cells were transfected with a plasmid expressing YFP-tagged SipB428-593, stained with an antibody to the mitochondrial protein CoxIV, subunit VIc (Molecular Probes, Inc.), and examined by confocal microscopy. SipB428-593-YFP localized to mitochondria and did not induce the formation of multivesicular structures seen after expression of the wild-type protein. ",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " (B) COS-2 cells were cotransfected with plasmids expressing either SipB428-593-YFP or SipB-CFP, and transfected cells were examined under a confocal microscope. Expression of SipB428-593-YFP prevented wild-type SipB-CFP from forming multivesicular structures (notice that vesicular structures are only apparent in the absence, but not in the presence, of SipB428-593-YFP; right). ",
    "ncbi_link": "SipB: 1254408"
  },
  {
    "caption": " The S. typhimurium SPI-1 TTSS-secreted protein SipB localizes to the mitochondria of infected macrophages. (A) Bone marrow-derived macrophages were infected with either wild-type S. typhimurium or the TTSS translocation-defective sipD mutant strain with a multiplicity of infection of 50. 3 h after infection, macrophages were collected and processed for immuno-EM using gold-labeled antibodies. SipB could be readily detected in macrophages infected with wild-type (A and B), but not in macrophages infected with the sipD mutant strain (C). Bars, 100 nm. ",
    "ncbi_link": "SPI-1: 
TTSS: 
sipD: 1254406"
  },
  {
    "caption": "S. typhimurium-infected macrophages exhibited signs of autophagocytosis. Caspase-1−/− BMDPM were infected with wild-type S. typhimurium or it isogenic translocation-defective sipD mutant. 6 h after infection, macrophages were either stained with MDC to label autophagosomes (I) or processed for EM (II) as described in the legend to Fig. 3. Macrophages infected with wild-type S. typhimurium (but not those infected with the sipD mutant) exhibited a large number of vesicular structures that stained with MDC (I)",
    "ncbi_link": "Caspase-1: 12362
sipD: 1254406"
  },
  {
    "caption": " Under the electron microscope (II), macrophages infected with wild-type Salmonella exhibited multivesicular structures resembling autophagosomes (A-D) Often, electron-dense material, presumably damaged organelles, were readily observed within the multivesicular structures (B-D). In contrast, macrophages infected with type III secretion-defective sipD mutant did not exhibit the large number of multivesicular structures observed in wild-type-infected cells. Bars (A and E) 500 nm; (B, C, D and F) 250 nm. ",
    "ncbi_link": "sipD: 1254406"
  },
  {
    "caption": " The S. typhimurium-induced macrophage death does not require caspase activity. BMDPM were infected with wild-type S. typhimurium or the TTSS-defective invG mutant in the presence or absence of 50 μM of the pan-caspase inhibitor Z-VAD, and cell death was measured as indicated in the legend to Fig. 1. ",
    "ncbi_link": "TTSS: 
invG: 1254421"
  },
  {
    "caption": " D) he effect of the pie1 and mbd9-1 mutations on the formation of the SWR1 complex as determined by IP-MS. Transgenic plants expressing Flag-tagged MBD9, PIE1, and CHR11 in the WT and mutant backgrounds were subjected to the IP-MS experiment with anti-Flag agarose. ",
    "ncbi_link": "mbd9: 821132
pie1: 820463"
  },
  {
    "caption": " (A) Morphological phenotypes of the WT, chr11/17, pie1, swc2, and rin2 mutant plants. Shown are 24-day-old plants. The top panel shows the phenotypes of plants in the soil; the bottom panel shows the phenotypes of plants on the black cloth. ",
    "ncbi_link": "chr11: 819814
pie1: 820463
rin2: 828626
swc2: 818246"
  },
  {
    "caption": " (B) Shown are rosette leaves of the WT, pie1, swc2, and rin2 mutant plants. Rosette leaves were cut from bolting plants. ",
    "ncbi_link": "pie1: 820463
rin2: 828626
swc2: 818246"
  },
  {
    "caption": " (C) The early-flowering phenotype of the mbd9-1, mbd9-3, mbd9-4 and hta9-1/11-1 mutants compared to the WT. 24-day-old plants in soil are shown. ",
    "ncbi_link": "hta9: 841707
mbd9: 821132"
  },
  {
    "caption": " (E) Determination of the effect of the arp4-1, arp6 and swc6-1 mutations on flowering time. The top panel shows the number of rosette leaves in the WT, arp4-1, arp6, and swc6-1 mutant plants; the bottom panel shows a photograph of the plants. Rosette leaves from at least 20 plants were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test. ",
    "ncbi_link": "swc6: 
arp4: 838425
arp6: 823150"
  },
  {
    "caption": " (F) Determination of the effect of the tra1a and tra1b mutations on flowering time. The top panel shows numbers of rosette leaves of the WT, tra1a-1, tra1a-2, and tra1b mutant plants; the bottom panel shows a photograph of the plants. Rosette leaves from at least 20 null were counted for each genotype. Values are mean ± SD. ** P<0.01, student's t test. ",
    "ncbi_link": "tra1a: 816303
tra1b: 829764"
  },
  {
    "caption": "(B) Heat maps showing the effect of indicated mutations on the expression of differentially expressed genes identified in the mbd9-1 mutant. The color bar shows log2(fold change). Up- and down-regulation are shown by red and blue, respectively.",
    "ncbi_link": "mbd9: 821132"
  },
  {
    "caption": " (C) Scatter plots showing that the expression pattern in the hta9-1/11-1 mutant is correlated with that in the chr11/17, mbd9-1, and pie1 mutants. The differentially expressed genes identified in the hta9-1/11-1 mutant were subjected to the analysis. ",
    "ncbi_link": "chr11: 819814
hta9: 841707
mbd9: 821132
pie1: 820463"
  },
  {
    "caption": " (D) Heat maps showing H2A.Z enrichment in the WT, pie1, chr11/17, and mbd9-1 mutants over the PIE1 -dependent H2A.Z target genes. The peaks were sorted by H2A.Z density in the WT.",
    "ncbi_link": "chr11: 819814
mbd9: 821132
pie1: 820463
PIE1: 820463"
  },
  {
    "caption": " (E) Shown are H2A.Z changes in the pie1, chr11/17, and mbd9-1 mutants relative to the WT. PIE1-dependent H2A.Z target genes were subjected to the analysis and sorted by H2A.Z density in the WT. The color bar shows log2(fold change). ",
    "ncbi_link": "chr11: 819814
mbd9: 821132
pie1: 820463
PIE1: 820463"
  },
  {
    "caption": " (F) Meta plots showing CHR11 and PIE1 occupancy on PIE1-dependent H2A.Z target genes. TSS, transcription start site; TTS, transcription termination site. The CHR11-Flag and PIE1-Flag ChIP-seq data are from two independent biological replicates. ",
    "ncbi_link": "Flag: 
CHR11: 819814
PIE1: 820463"
  },
  {
    "caption": "(G) Heat maps showing the enrichment of PIE1-Flag and CHR11-Flag over the PIE1-dependent H2A.Z target genes. The peaks were sorted by H2A.Z density in the WT.",
    "ncbi_link": "Flag: 
CHR11: 819814
PIE1: 820463"
  },
  {
    "caption": " (H) Box plot showing the enrichment of CHR11 and PIE1 over H2A.Z target genes and non-H2A.Z target genes. The log2(fold change) values of RPKM between the CHR11-Flag or PIE1-Flag signals and the WT signals are shown. Center lines and box edges represent medians and the interquartile range (IQR), respectively. Whiskers extend to minimum and maximum values within 1.5 times of the IQR. The data shown are from two independent biological replicates. The difference between the CHR11-Flag and PIE1-Flag ChIP-seq levels was determined by student's t test. ** P<0.01. ",
    "ncbi_link": "Flag: 
CHR11: 819814
PIE1: 820463"
  },
  {
    "caption": "(B) Distribution of nucleosomes over TSS of all protein-coding genes in the WT, chr11/17, pie1, and mbd9-1 mutants. The MNase-seq results were generated from two independent biological replicates.",
    "ncbi_link": "chr11: 819814
mbd9: 821132
pie1: 820463"
  },
  {
    "caption": "(D) (top) Schematics of the different PRR7 constructs used for co-IP (FL= full length). (bottom) PRR7 deletion constructs and NMDAR subunits were expressed in HEK293 cells and Co-IPs performed as indicated.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(A) Western blots of lysates of primary neurons transduced with control lentiviruses (NT) or lentiviruses to knockdown (KD) or overexpress (OE) PRR7. PRR7 knockdown reduced (75.6 ± 6.9%) while PRR7 overexpression (OE) increased (157.6 ± 22.8%) c-Jun levels compared to controls. No change was detected in c-Fos levels. One-way ANOVA test was used to analyze results with Dunett's post hoc test (n=16 gels for c-Jun and 4 gels for c-Fos).",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(B) Control or PRR7 transfected HEK293 cells were treated with cycloheximide for the indicated time points and c-Jun protein levels were measured by Western blotting. PRR7 expression significantly stabilized c-Jun levels at 120 min (110.0 ± 7.5% vs control 68.7 ± 7.9%) and 240 minutes (83.6 ± 5.2% vs control 43.7 ± 3.4%). Values for c-Jun were normalized to their respective 0 min time point (n=4 gels for each group performed blind). T-tests between similar time points were used to analyze results.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(C) PRR7, FBW7 and/or a control protein (PSD95) were transfected into HEK293 cells and c-Jun ubiquitination was measured by immunoprecipitating c-Jun and blotting for ubiquitin. Ubiquitination of c-Jun in the presence of FBW7 (178.3 ± 26.9%) was significantly reduced in the presence of PRR7 (103.7 ± 20.6%) but not a control protein (PSD95) (n=5 gels for all groups).",
    "ncbi_link": "PSD95: 29495
FBW7: 100360914
PRR7: 498704"
  },
  {
    "caption": "(D) Western blots of c-Junubiquitination in hippocampal primary neuronal cultures. PRR7 knockdown (KD) elevated (149±10.62%, n=6 gels) c-Junubiquitination level in comparison to control neurons (NT). Statistical significance was determined by t-test.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(A) Co-IPs of PRR7 with c-Jun from lysates of HEK293 cells overexpressing PRR7.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(A) Western blots of phospho-c-Jun in primary neuronal cultures. Quantification of phospho-c-Jun represents a ratio of phospho-c-Jun to total c-Jun and all ratios were normalized to NT. PRR7 knockdown (KD) decreased, while PRR7 overexpression (OE) increased phospho-c-Jun levels (black bars). Glutamate stimulation (gray bars) increased phospho-c-Jun/c-Jun ratio in NT but not in KD or OE neurons (n=7 gels for all groups). Significance was determined using two-way ANOVA with Sidak post-hoc test.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(B) AP-1 driven luciferase luminescence assays. PRR7 expression in HEK293 cells increased AP-1 activity (190.6 ± 13.9%, n=12; RLU= relative light units). Statistical significance was determined using t-tests.",
    "ncbi_link": "AP-1: 3725"
  },
  {
    "caption": "(D) Quantitation of cell death using 30 minutes of PI in-situ staining following 48h of WT-PRR7-GFP or mNLS-PRR7-GFP overexpression in primary hippocampal neuronal cultures (n=24 cells per group). Images represent a max projection of five z-stack sections across the cell body.",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(E) NMDA treatment (25 min, 100 µM followed by 14h chase) caused 83.6±3.5% cell death in control neurons compared to 60.3±4.6% cell death in neurons with PRR7 expression knocked down. A c-Jun inhibitory peptide reduced NMDA-mediated cell death to 66.2±6.0% in control neurons and to 55.6±5.3% in neurons knocked down for PRR7, but this difference was not statistically significant (n=5 independent experiments). Two-way ANOVA was used in conjugation with Tukey post-hoc test. (Left) Representative images showing transduced neurons (green- GFP) and PI staining (red).",
    "ncbi_link": "PRR7: 498704"
  },
  {
    "caption": "(F) Quantification of cell death in response to NMDA stimulation in the presence or absence of PRR7 and either WT c-Jun or a dominant negative c-Jun4A (4A). Overexpression of WT c-Jun caused extensive neuronal cell death (84.8±2.4%) that was reduced in neurons knocked down for PRR7 (43.8±9.2). Overexpressing 4A conferred neuroprotection to NMDA excitotoxicity (50.8±7.9%) but was not additive with PRR7 knockdown (42.3±8.1%) (n=3 independent experiments). Significance was determined using two-way ANOVA in conjugation with Tukey post-hoc test. Images are representative 10X widefield micrographs showing transduced neurons (green- GFP) and PI staining (red). Data is presented as mean±sem. All % values represent comparisons to control.",
    "ncbi_link": "c-Jun: 16476
PRR7: 498704"
  },
  {
    "caption": "(B) Age- and sex-matched Atx∆ΜΕ/∆ΜΕ;Il10-/- mice (n=9) and Atx+/+;Il10-/- littermates (n=9) were examined for the development of spontaneous colitis. Body weight changes were monitored every other day, starting at the age of 37 days and ending at the age of 6 months. Results are means ± SD. Data were compared by Two-way ANOVA (with treatment and times), followed by the multiple-comparison Bonferroni t test to assess differences between groups.",
    "ncbi_link": "Atx: 18606
Il10: 16153"
  },
  {
    "caption": "(G) Survival of Atx∆ΜΕ/∆ΜΕ;Il10-/- (n=17) and Atx+/+;Il10-/- littermates (n=18) was analyzed by the Kaplan-Meier method (Log-rank P=0.0046).",
    "ncbi_link": "Atx: 18606
Il10: 16153"
  },
  {
    "caption": "(A) Total cell lysates of peritoneal macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates were subjected to immunoblotting analysis to confirm Atx deletion.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The physical interaction of TLR4-CD14 was examined by FRET analysis. HEK293 cells were transfected with TLR4-EYFP (yellow) and CD14-ECFP (blue) (C) followed by ATX inhibitor (50 μM, 30 min) or vehicle treatment (Veh, DMSO 0.1%). Cells were washed with PBS and fixed, then visualized with filter sets for CFP and YFP. FRET images were visualized with the FRET filter set, expressed as corrected FRET efficiency and displayed in quantitative pseudocolor indicating the distance between proteins (arbitrary linear units of fluorescence intensity). Presented are the representative images from at least three independent experiments. Scale bar indicates 5 μm.",
    "ncbi_link": "ECFP: 
EYFP: 
CD14: 12475
TLR4: 21898"
  },
  {
    "caption": "The physical interaction of TLR4-TLR4 was examined by FRET analysis. HEK293 cells were transfected with TLR4-EYFP and TLR4-ECFP (D), followed by ATX inhibitor (50 μM, 30 min) or vehicle treatment (Veh, DMSO 0.1%). Cells were washed with PBS and fixed, then visualized with filter sets for CFP and YFP. FRET images were visualized with the FRET filter set, expressed as corrected FRET efficiency and displayed in quantitative pseudocolor indicating the distance between proteins (arbitrary linear units of fluorescence intensity). Presented are the representative images from at least three independent experiments. Scale bar indicates 5 μm.",
    "ncbi_link": "ECFP: 
EYFP: 
TLR4: 21898"
  },
  {
    "caption": "(A and B) Peritoneal macrophages from Atx+/+ (A) and Atx∆ΜΕ/∆ΜΕ (B) mice were stimulated with LPS (20 ng/mL, 20 min), followed by fixation in 4% paraformaldehyde for 15 min at room temperature and staining with TLR4-anti rabbit FITC (Green), early endosomal marker EEA1-anti mouse Dylight405 (Blue), and Alexa Fluor 594-CTXB (Red). TLR4 internalization was examined with confocal microscopy. Presented are the representative from 3 independent experiments in which more than 95% of the cells exhibited similar results. Scale bar, 10 μm.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ and Atx+/+ mice were stimulated with LPS (20 ng/mL, 20 min) The cell lysates were subjected to immunoprecipitation (IP), followed by immunoblotting (IB) analysis with the antibodies indicated. Presented is the representative from three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ and Atx+/+ mice were stimulated with LPS (20 ng/mL, 20 min) The cell lysates were subjected to immunoprecipitation (IP), followed by immunoblotting (IB) analysis with the antibodies indicated. Presented is the representative from three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ and Atx+/+ mice were stimulated with LPS (20 ng/mL, 20 min) The cell lysates were subjected to immunoprecipitation (IP), followed by immunoblotting (IB) analysis with the antibodies indicated. Presented is the representative from three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ and Atx+/+ mice were stimulated by LPS [20 ng/mL, 20 min : The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. Regular ERK1/2, were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ and Atx+/+ mice were stimulated by LPS [20 ng/mL, 20 min The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. regular Akt were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "Atx-heterozygous (Atx-Het) mice and wild type littermates (C) were stimulated by LPS indicated time point The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. RasGAP levels were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates were activated with TLR2 ligand Peptidoglycan (PGN, 30 ng/mL) (E) for the indicated time points. The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. Regular ERK1/2 were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates were activated with Pam3CSK4 (1 μg/mL) (F) for the indicated time points. The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. Regular ERK1/2 were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates were activated with IL-1β (100 ng/mL) for the indicated time points. : The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. Regular ERK1/2 were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "The macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates were activated with TNFα (25 ng/mL) (H) for the indicated time points. The cell lysates were subjected to immunoblotting analysis with antibodies as indicated. Regular ERK1/2 were used for a loading control. Presented are the representative image from at least three independent experiments.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "Peritoneal macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates (A) were stimulated with LPS (50 ng/mL, 8 h) The culture medium was collected for ELISA to measure the level of secreted cytokines. All assays were performed in triplicate, and data are shown as mean ± SEM.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "(F) To induce sepsis via LPS injection (Shirey et al., 2013; Voss et al., 2016), age (9-10 weeks)- and sex-matched Atx∆ΜΕ/∆ΜΕ mice (n = 9) and Atx+/+ littermates (n = 21) were injected with LPS (i.p. 25 mg/kg). Survival was monitored for up to 16 h, and analyzed by the Kaplan-Meier method (Log-rank P=0.0004).",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "(G) Blood samples were collected from Atx∆ΜΕ/∆ΜΕ (n = 7) and Atx+/+ (n = 6) mice 10 h after LPS injection, after which the serum TNFα protein level was measured. The data are shown as mean ± SEM.",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "Confocal laser scanning micrographs of the macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates. Cells were incubated with IgG-opsonized latex beads in the absence/presence of LPS (20 ng/mL, 2 h) and stained with Phalloidin (F-actin) and DAPI. Internalized beads were examined under a higher(A)",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "Confocal laser scanning micrographs of the macrophages from Atx∆ΜΕ/∆ΜΕ mice and Atx+/+ littermates. Cells were incubated with IgG-opsonized latex beads in the absence/presence of LPS (20 ng/mL, 2 h) and stained with Phalloidin (F-actin) and DAPI. Internalized beads were examined under a lower magnification (B) to quantify % phagocytosis by dividing latex bead-positive cell numbers by the total number of DAPI-positive cells (n=11 - 16 per group). The data are analyzed with results accumulated from three independent experiments and shown as mean ± SEM (B). **P < 0.01 (Mann-Whitney U test).",
    "ncbi_link": "Atx: 18606"
  },
  {
    "caption": "After LPS (20 ng/mL, 4 h) treatment, LPS-induced iNos, Arginase-1 (Arg-1), and Ym-1 mRNA expression were evaluated by semi-quantitative PCR (D).",
    "ncbi_link": "Arg-1: 11846
Arginase-1: 11846
Ym-1: 12655
iNos: 18126"
  },
  {
    "caption": "(A) Confocal live cell imaging of HeLa cells overexpressing GFP-Bax (green) and mitochondria marked with TMRE 100 nM (magenta) show cytosolic GFP-Bax distribution and healthy mitochondria. Lower panels are zoomed images corresponding to the white rectangle in the upper panel and represent the individual and merged channels. Time shows the minutes after apoptosis induction with Staurosporine (STS) 1 µM. Scale bars, 5µm (overview) and 2µm (zooms)(B) HeLa cells shown in A at longer times after STS treatment. Images show sequential GFP-Bax translocation (green), which correlates with mitochondria depolarization (TMRE, magenta). Scale bars, 5 µm(C) HeLa cells overexpressing GFP-Bax mutant (1-2/L-6) (green) and mitochondria marked with TMRE 100 nM (magenta). Images show constitutive GFP-Bax localization to healthy mitochondria without apoptosis induction. Right panels are zoomed images corresponding to the white rectangle in the left panel and represent the individual and overlaid channels. Scale bars, 5µm (overview) and 2 µm (zooms)(D) Standard deviation of the fluorescence intensity of GFP-Bax blue) versus the corrected total cell fluorescence (CTCF) of TMRE (purple) in individual cells (N=4). CTCF= Integrated Density - (Area of selected cell X Mean fluorescence of 3 background readings). Time 0 corresponds to the normalized time when both events cross in each cell. Black line represents the average of the individual cells.",
    "ncbi_link": "Bax: 581"
  },
  {
    "caption": "(A) Overview of a reconstructed superresolution image of GFP-Bax overexpressing HeLa cells stained with AF647-anti-GFP-nanobodies. Image was acquired on fixed cells 3 h after apoptosis induction with STS. Dotted line shows the cell shape (see Fig EV3). Scale bar, 5 µm.(B) Magnified reconstructed superresolution image corresponding to the white rectangle in A showing the shapes of GFP-Bax WT structures (white arrows). Scale bar, 500 nm.(C) Gallery of typical GFP-Bax WT structures during apoptosis found in all the analyzed cells. Scale bars, 100 nm.(D) Overview (left) and 3 enlarged insets (right) of HeLa cells overexpressing GFP-Bax 1-2/L-6 stained with AF647-anti-GFP-nanobodies. Figure shows reconstructed superresolution images acquired without apoptosis induction. Scale bars, 5 µm (overview) and 500 nm (insets).",
    "ncbi_link": "Bax: 581"
  },
  {
    "caption": "(A) Quantification of the structures found on Bax wild type (purple) and on Bax 1-2/L-6 (grey) overexpressing cells. Data show the total number of structures in all the measurements. n (Bax wild type)= 13, n (Bax 1-2/L-6)=11.(B) Cumulative distribution plots of GFP-Bax wild type (purple) and GFP-Bax 1-2/L-6 (grey) showing differences in amplitude and frequency. Each plot represents a single cell. Thick lines represent average cumulative distributions for all the single cells transfected with GFP-Bax WT or mutant GFP-Bax 1-2/L-6.",
    "ncbi_link": "Bax: 581"
  },
  {
    "caption": "(A) Overview of a reconstructed superresolution image of GFP-Bax overexpressing HCT116Bax/Bak -/- cells stained with AF647-anti-GFP-nanobodies Image was acquired on fixed cells 7 h after apoptosis induction with STS. Dotted line shows the cell shape (see Fig EV3). Scale bar, 5 µm.(B) Gallery of typical GFP-Bax WT non-random structures during apoptosis on HCT116Bax/Bak -/- cells. Scale bars, 100 nm.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "(A) AFM image of a control SLB prepared from LUVs with a mitochondrial-like lipid composition. The bilayer looks flat, without aggregates or defects. Scale bar, 1 µm.(B) AFM image of a SLB prepared from LUVs with a mitochondrial-like lipid composition pre-incubated with heat-activated Bax. The green arrows indicate the presence of membrane pores, which are heterogeneous in size and shape. The edges of the pores present protrusions corresponding to Bax clusters. Scale bar, 1 µm.",
    "ncbi_link": "Bax: 581"
  },
  {
    "caption": "Sqr mRNA levels (A, B, C), in cerebrum (A, D), kidneys (B, E, G) and muscle (C, F, H) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914
Sqr: 59010"
  },
  {
    "caption": "SQR protein levels (D, E, F) in cerebrum (A, D), kidneys (B, E, G) and muscle (C, F, H) of Coq9+/+, Coq9R239X and Coq9Q95X mice. Note that SQRwestern-blots were performed in isolated cerebralmitochondria due to the low levels of this protein in cerebrum. In kidneys and muscle the western-blots were performed in tissue homogenates.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "SQR activity (G, H) in kidneys (B, E, G) and muscle (C, F, H) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Levels of CoQ10 in fibroblasts of controls (C) and patients (P1-4) with primary CoQ10 deficiency (A).",
    "ncbi_link": "CoQ10: 80219///93058"
  },
  {
    "caption": "Levels of SQR protein in fibroblasts of controls (C) and patients (P1-4) with primary CoQ10 deficiency cultured without (vehicle) and with 5μM of CoQ10 (+ CoQ10) during 1 day or 7 days (B).",
    "ncbi_link": "CoQ10: 80219///93058"
  },
  {
    "caption": "Total CoQ levels (CoQ9 + CoQ10) in kidneys (C) and muscle (D) of Coq9+/+, Coq9R239X and Coq9R239X + ubiquinol-10 (Q10H2) mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Levels of SQR protein in kidneys (E) and muscle (F) of Coq9+/+, Coq9R239X and Coq9R239X + ubiquinol-10 (Q10H2) mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "TST protein levels in cerebrum (A), kidneys (B) and muscle (C) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "TST activity in cerebrum (D), kidneys (E) and muscle (F) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "ETHE1 (SDO) protein levels in cerebrum (G), kidneys (H) and muscle (I) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "SUOX protein levels in cerebrum (J), kidneys (K) and muscle (L) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Quantification of sulfide levels in cerebrum and kidneys of Coq9+/+, Coq9R239X and Coq9Q95X mice (A).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Qualitative measurement of hydrogen sulfide in cerebrum and kidneys of Coq9+/+ and Coq9R239X mice (B).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Total GSH in cytosol and mitochondria of cerebrum of Coq9+/+ and Coq9R239X mice(A).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Cytosolic GPx and GRd activities in cerebrum of Coq9+/+ and Coq9R239X mice (B).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Levels of GPx4 (C) and GRd (D) protein in cerebral homogenate of Coq9+/+ and Coq9R239X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Levels of L-Glutamate (L-Glu), N-Acetyl-Glutamate (NacGlu), L-Tryptophan (L-Trp), 5HIAA, N-Acetyl-Tryptophan (NALT), L-Tyrosine (L-Tyr) in cerebrum of Coq9+/+ and Coq9R239X mice (E).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "TST protein level in kidneys (C) and cerebrum (D) of Coq9+/+ mice supplemented with the H2S donor GYY4137.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Levels of neurotransmitters in cerebrum of Coq9+/+ mice supplemented with the H2S donor GYY4137 (E).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "COX activity in cerebrum, kidneys and muscle (A) of Coq9+/+, Coq9R239X and Coq9Q95X mice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Images COX histochemistry (B) in gastrocnemious of Coq9+/+, Coq9R239X and Coq9Q95X mice; scale bars: 100 μm.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Systolic, diastolic and mean blood pressure in Coq9+/+ and Coq9R239X mice (A).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Heart rate in Coq9+/+ and Coq9R239X mice (B). **P < 0.01; Coq9R239X mice versus Coq9+/+ mice (t test; n = 5 for each group).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A, PTPN3 promotes TGF-β-induced CAGA-luc reporter gene activity. HaCaT cells were transfected with expression plasmids for CAGA-luc reporter gene, Renilla-luc reporter gene and PTPN3 as indicated and treated with TGF-β (2 ng/mL, 8 h). Relative luciferase activity was measured Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. ***P < 0.001.",
    "ncbi_link": "luc: 
PTPN3: 5774"
  },
  {
    "caption": ", Knockdown of PTPN3 decreases TGF-β-induced CAGA-luc reporter gene activity. HaCaT cells were transfected with siRNA against PTPN3 or control siRNA. 24 h post-transfection, expression plasmids for CAGA-luc reporter and Renilla-luc reporter were transfected as indicated. Cells were harvested for relative luciferase assay after another 24 h with TGF-β treatment (2 ng/mL, 8 h). Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. ***P < 0.001.",
    "ncbi_link": "luc: 
PTPN3: 5774"
  },
  {
    "caption": "C, Knockdown of PTPN3 blocks TGF-β-induced p21 transcription. HaCaT cells were transfected with two independent siRNAs against PTPN3 and treated with TGF-β (2 ng/mL) for 8 h before harvested. Total mRNA was analyzed by qRT-PCR using primers specific to p21. Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. **P<0.01, ***P < 0.001.",
    "ncbi_link": "p21: 1026
PTPN3: 5774"
  },
  {
    "caption": "D, Knockdown of PTPN3 blocks TGF-β-induced PAI-1 gene transcription. Experiment was done with qRT-PCR primers specific to PAI-1. Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. ***P < 0.001.",
    "ncbi_link": "PTPN3: 5774
PAI-1: 5054"
  },
  {
    "caption": "E, Knockdown of PTPN3 abolishes TGF-β-induced p21 transcription. HaCaT cells were transfected with siRNA and then treated with TGF-β (2 ng/mL) for 0, 4, 8 or 24 h as indicated. qRT-PCR was carried out Data are shown as mean ± SEM; n = 3.",
    "ncbi_link": "p21: 1026
PTPN3: 5774"
  },
  {
    "caption": "F, Knockdown of PTPN3 abolishes TGF-β-induced transcription of PAI-1. Experiment was done Data are shown as mean ± SEM; n = 3.",
    "ncbi_link": "PTPN3: 5774
PAI-1: 5054"
  },
  {
    "caption": "G, Depletion of PTPN3 abolishes TGF-β-induced target protein expression. HaCaT cells with stable knockdown of PTPN3 were treated with TGF-β (2 ng/mL) for 6 h before harvested. Cells were harvested for Western blotting with anti-p21, anti-PAI-1, anti-PTPN3 and anti-β-Actin antibodies.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "H, PTPN3 enhances TGF-β-induced target protein expression. HaCaT cells stably expressing HA-PTPN3 were stimulated with 2 ng/mL of TGF-β for 6 h and then harvested for cell lysates. Protein levels were examined by Western blotting with appropriate antibodies as indicated.",
    "ncbi_link": "HA: 
PTPN3: 5774"
  },
  {
    "caption": "I, Depletion of PTPN3 attenuates TGF-β global gene responses. Venn diagram shows the number of differential expression genes (DEGs) with TGF-β treatment in control or PTPN3-depleted HaCaT cells by RNA-Seq analysis. The overlap represents TGF-β target genes that are commonly regulated in both cell lines. HaCaT cells transfected with siControl or siPTPN3 were harvested for RNA-Seq after treated with or without TGF-β (2 ng/mL, 8 h).",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "J, Loss of PTPN3 markedly decreases TGF-β-dependent upregulation or downregulation of target genes. Heat map of DEGs in control HaCaT cells (siControl) or HaCaT cells depleted of PTPN3 (siPTPN3). Log2FC data represent fold change of TGF-β (2 ng/mL) treatment over vehicle for 8 h.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "B, Both PTPN3 and PTPN3 (L232R), but not the phosphatase-dead mutants PTPN3 (D811A) and PTPN3 (C842S), dephosphorylate P-EGFR (Y1173). Wildtype PTPN3 or its mutants were co-transfected with EGFR into HEK293T cells as indicated. 24 h later, cells were harvested for Western blotting. Levels of P-EGFR (Y1173), EGFR, PTPN3 and its mutants were examined by appropriate antibodies.",
    "ncbi_link": "EGFR: 1956
PTPN3: 5774"
  },
  {
    "caption": "C, PTPN3 and PTPN3 (D811A) enhance TGF-β-induced target protein expression. HaCaT cells stably expressing HA-PTPN3 or HA-PTPN3 (D811A) were stimulated with 2 ng/mL of TGF-β for 6 h and then harvested for cell lysates. Protein levels were examined by Western blotting with appropriate antibodies as indicated.",
    "ncbi_link": "HA: 
PTPN3: 5774"
  },
  {
    "caption": "D, PTPN3 and its catalytically inactive mutants PTPN3 (D811A) and PTPN3 (C842S) equally enhance TGF-β-induced reporter gene activity. HaCaT cells were transfected with expression plasmids for each PTPN3 variant and CAGA-luc reporter and Renilla-luc reporter. Cells were harvested for relative luciferase assay after TGF-β (2 ng/mL, 8 h) treatment. Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. ***P < 0.001.",
    "ncbi_link": "luc: 
PTPN3: 5774"
  },
  {
    "caption": "E, PTPN3 FERM domain enhances TGF-β-induced reporter gene activity as potently as wildtype PTPN3. HaCaT cells were transfected with expression plasmids for PTPN3 truncations and CAGA-luc reporter, and internal control Renilla-luc reporter. Cells were harvested for relative luciferase assay with TGF-β treatment (2 ng/mL, 8 h). Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. **P<0.01, ***P<0.001. NS, non-significant.",
    "ncbi_link": "luc: 
PTPN3: 5774"
  },
  {
    "caption": "A, PTPN3 and PTPN3 (D811A) stabilize TβRI. TβRI and PTPN3 were detected by Western blotting with appropriate antibodies as indicated in HaCaT cells stably expressing PTPN3 or PTPN3 (D811A).",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "B, shRNA PTPN3-mediated reduction of endogenous TβRI level is restored by MG132. HaCaT cells expressing shRNA PTPN3-1, shRNA PTPN3-2 or control shRNA were treated with MG132 (20 μM) for 4 h. Cell lysates were analyzed by Western blotting with anti-TβRI, anti-PTPN3 and anti-GAPDH antibodies.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "C, PTPN3 rescues the degradation of TβRI induced by Smurf2. HEK293T cells were transfected with the indicated plasmids. Cells were harvested after 24 h post-transfection. Western blotting was done with the indicated antibodies.",
    "ncbi_link": "PTPN3: 5774
Smurf2: 64750"
  },
  {
    "caption": "D, PTPN3 and PTPN3 (D811A) attenuate ubiquitination of TβRI. HEK293T cells were transfected with the indicated plasmids. 24 h after transfection, IP and immunoblotting analysis were performed with the anti-FLAG antibody. Levels of TβRI ubiquitination and other proteins were examined by Western blotting with the indicated antibodies.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "E, PTPN3 blocks Smurf2-mediated ubiquitination of TβRI. HEK293T cells were transfected with the indicated plasmids, and treated with MG132 (20 μM, 4 h) before harvest. TβRI IP was performed with the anti-HA antibody, and TβRI ubiquitination was determined by Western blotting with the anti-Myc antibody. Protein levels were examined by Western blotting with the indicated antibodies.",
    "ncbi_link": "PTPN3: 5774
Smurf2: 64750"
  },
  {
    "caption": "F, Depletion of Smurf2 reverses the shPTPN3-induced degradation of TβRI. HEK293T cells were transfected with expression plasmids for shPTPN3, shSmurf2 and HA-TβRI. 48 h post-transfection, cells were harvested for immunoblotting analysis. TβRI level was determined by Western blotting with the anti-HA antibody. Levels of other proteins were done by Western blotting with the indicated antibodies.",
    "ncbi_link": "HA: 
PTPN3: 5774
Smurf2: 64750
TβRI: 7046"
  },
  {
    "caption": "G, Dominant negative Smurf2 mutant C716A prevents shPTPN3-induced TβRI degradation. HaCaT cells stably expressing shPTPN3 were transfected with FLAG-Smurf2 (C716A). Cells were harvested for Western blotting with anti-TβRI, anti-FLAG, anti-PTPN3 and anti-GAPDH antibodies.",
    "ncbi_link": "FLAG: 
PTPN3: 5774
Smurf2: 64750"
  },
  {
    "caption": "B, Both PTPN3 and PTPN3 (D811A) interact with TβRI. FLAG-TβRI was co-transfected with HA-PTPN3 or HA-PTPN3 (D811A) into HEK293T cells. Cell lysates were harvested and subjected to IP with FLAG antibody. PTPN3, PTPN3 (D811A) and TβRI were detected by Western blotting with appropriate antibodies.",
    "ncbi_link": "FLAG: 
HA: 
PTPN3: 5774
TβRI: 7046"
  },
  {
    "caption": "C, The FERM domain of PTPN3 is necessary for its binding to TβRI. FLAG-TβRI and HA-PTPN3 (wildtype or truncations) were co-transfected into HEK293T cells. Cells were harvested after 24 h and subjected to IP by HA antibody. TβRI, PTPN3 and PTPN3 truncations were detected by Western blotting with appropriate antibodies.",
    "ncbi_link": "FLAG: 
HA: 
PTPN3: 5774
TβRI: 7046"
  },
  {
    "caption": "E, Knockdown of endogenous PTPN3 promotes the Smad7-TβRI association. HEK293T cells were transfected with the indicated plasmids and treated with MG132 (20 µM) for 4 h before harvested. SFB-Smad7 proteins were retrieved with the Streptavidin pulldown. Levels of TβRI and other proteins were examined by Western blotting with the indicated antibodies.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "F, PTPN3 and PTPN3 (D811A) abolish the interaction between TβRI and Smurf2 in HEK293T cells. HEK293T cells were co-transfected with plasmids as indicated. 20 h later, cells were treated with MG132 (20 μM) for 4 h, followed by IP and Western blotting.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "A, PTPN3 wildtype, phosphatase-dead D811A and ICC-derived mutant L232R exhibit similar patterns of subcellular localization and co-localization with TβRI. HaCaT cells were transfected with HA-TβRI and Flag-PTPN3 (wildtype or its mutants). 24 h later, cells were harvested for immunofluorescence with the indicated antibodies. Scale bar = 10 μm.",
    "ncbi_link": "Flag: 
HA: 
PTPN3: 5774
TβRI: 7046"
  },
  {
    "caption": "B, PTPN3 (L232R) does not increase the TβRI protein level. TβRI and PTPN3 were determined by Western blotting in HaCaT cells stably expressing PTPN3, PTPN3 (D811A) or PTPN3 (L232R).",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "C, PTPN3 (L232R) fails to rescue the Smurf2-mediated degradation of TβRI. HEK293T cells were transfected with FLAG- TβRI, Myc-Smurf2 and the increasing anount of PTPN3 (wildtype and mutants). Cells were harvested 24 h post-transfection. Protein levels were examined by Western blotting with the indicated antibodies.",
    "ncbi_link": "FLAG: 
Myc: 
PTPN3: 5774
Smurf2: 64750
TβRI: 7046"
  },
  {
    "caption": "D, PTPN3 (L232R) does not block the interaction between TβRI and Smurf2. HEK293T cells were co-transfected with plasmids as indicated. 20 h later, cells were treated with MG132 (20 μM) for 4 h and analyzed by IP-Western blotting.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "E, Ectopic expression of PTPN3 wildtype and PTPN3 (D811A), but not PTPN3 (L232R), completely abolishes the Smad7-TβRI interaction. HEK293T cells were co-transfected with plasmids as indicated. 20 h later, cells were treated with MG132 (20 µM) for 4 h, followed by IP and Western blotting.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "F, PTPN3 and PTPN3 (D811A), but not PTPN3 (L232R), attenuate ubiquitination of TβRI. HEK293T cells were transfected with the indicated plasmids. 24 h after transfection, IP-Western blotting analysis was performed with anti-Flag antibody IP and followed by Western blotting with the indicated antibodies.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "A, PTPN3 and PTPN3 (D811A), but not PTPN3 (L232R), enhance Smad2 and Smad3 phosphorylation. HaCaT cells were stimulated with TGF-β (2 ng/mL) for 1 h. Levels of P-Smad2, P-Smad3, Smad2, Smad3, PTPN3 and GAPDH were detected by Western blotting.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "B, PTPN3 (L232R) inhibits TGF-β-induced reporter gene activity. HepG2 cells were transfected with expression plasmids for PTPN3, PTPN3 mutants and CAGA-luc reporter, and Renilla-luc reporter. Cells were harvested for luciferase assay after 8 h of TGF-β (2 ng/mL) treatment. Data are shown as mean ± SEM; n = 3. Statistical analysis was performed using two-tailed Student's t-test. *P<0.05, **P<0.01.",
    "ncbi_link": "luc: 
PTPN3: 5774"
  },
  {
    "caption": "C, PTPN3 and PTPN3 (D811A), but not PTPN3 (L232R), enhance TGF-β-induced growth inhibitory effect. HepG2 cells stably expressing PTPN3, PTPN3 (D811A) or PTPN3 (L232R) were treated with or without TGF-β (1 ng/mL) for indicated days. Cells were analyzed for cell proliferation by MTS assay. Data are shown as mean ± SEM; n = 3.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "D, Depletion of PTPN3 attenuates TGF-β-induced growth inhibitory effect. HepG2 cells stably expressing shPTPN3 were treated with or without TGF-β (1 ng/mL) for indicated days. Cells were analyzed for cell proliferation by using MTS assay. Data are shown as mean ± SEM; n = 3.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "E, PTPN3 (L232R) attenuates TGF-β-induced growth inhibition on colony formation in HepG2 cells. Cells were treated with or without TGF-β (1 ng/mL) treatment for 10 days. Clonogenic assay Quantification of the results in clonogenic assays was analyzed by Image J. Data are shown as mean ± SEM; n = 3.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "F, Depletion of PTPN3 attenuates TGF-β-induced growth inhibitory effect in HepG2 cells. Cells with stable knockdown of PTPN3 were treated with or without TGF-β (1 ng/mL) for 10 days. Clonogenic assay Quantification of the results in clonogenic assays were analyzed by Image J. Knockdown efficiency of PTPN3 in HepG2 cells were analyzed by Western blotting with the anti-PTPN3 antibody. Data are shown as mean ± SEM; n = 3. G, Depletion of PTPN3 attenuates TGF-β-induced growth inhibitory effect in Huh7 cells. Experiments and analysis were similarly done as in (F). Data are shown as mean ± SEM; n = 3. ",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "B, PTPN3 and PTPN3 (D811A), but not PTPN3 (L232R), attenuates tumorigenesis. Luciferase-harboring Huh7 tumor cells (2 × 106 cells/mouse) expressing PTPN3, PTPN3 (D811A) or PTPN3 (L232R) or empty vector (served as negative control) were subcutaneously injected into 5-week-old nude mice. Twenty days after injection, mice were analyzed by bioluminescence using Xenogen IVIS imaging system. Tumors expressing luciferase is indicated by radiance bar (p/sec/cm2/sr). C, Quantitation of bioluminescence with data from (B). Data are shown as mean ± SEM; n = 5. ",
    "ncbi_link": "Luciferase: 
luciferase: 
PTPN3: 5774"
  },
  {
    "caption": "D, Depletion of PTPN3 accelerates tumorigenesis. HepG2 cells stably expressing shPTPN3 or shControl were subcutaneously injected into nude mice. Fifty days after cell implantation, tumors were dissected and photographed.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "E, Depletion of PTPN3 increased tumor sizes. Tumor volume was measured at indicated days post-implantation. Data are shown as mean ± SEM; n = 6 for each group. F, Depletion of PTPN3 increased tumor weight. Weight from all tumors was recorded from both control and shPTPN3 groups. Data are shown as mean ± SEM; n = 6 for each group. ",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": ", PTPN3 depletion impairs TGF-β signaling in tumors. Levels of PTPN3, GAPDH and TGF-β signaling associated proteins, such as TβRI, P-Smad2, P-Smad3, Smad2/3, Smad4, PAI-1, c-Myc and p15 in tumors were analyzed by Western blotting analysis.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "H, Clinical significance of PTPN3 expression in LIHC based on TCGA database. In the boxplots, Y-axis represents the expression level of PTPN3 in normal and tumor samples. The boxes show the median (horizontal line in the box) ± 1 quartile; the upper and lower box limits represent the upper and lower quartiles, respectively. The whiskers (vertical lines) extend from the hinge to the smallest or larget value within 1.5 interquartile range from the box boundaries.",
    "ncbi_link": "PTPN3: 5774"
  },
  {
    "caption": "A. In situ hybridization for GemC1 and McIdas mRNA was performed on sagittal sections of E10.5 dpc mouse brain. GemC1 and McIdas mRNA is specifically detected in the developing choroid plexuses of the ventricles. Lower panels show higher magnifications. Scale bars, 100 µm.",
    "ncbi_link": "GemC1: 239789
McIdas: 622408"
  },
  {
    "caption": "B. In situ hybridization on sagittal (upper) and coronal (middle and lower) sections of the airways of E15.5 dpc mouse embryos, depicting specific GemC1 and McIdas mRNA expression in the respiratory epithelium of the nasal and oral cavity and in the upper bronchial tree in the mouse lungs. Inserts show higher magnification images. Scale bars, 200 µm.",
    "ncbi_link": "GemC1: 239789
McIdas: 622408"
  },
  {
    "caption": "C. MTECs were cultured ex-vivo and transitioned to ALI culture condition. Quantitative real time PCR was used to measure the expression levels of GemC1, McIdas, FoxJ1 and Geminin mRNA levels at different time points during multiciliogenesis. Values indicate expression levels (+/- standard error, s.e.) relative to ALI DAY 1 (marked by *), following normalization against the house-keeping HPRT mRNA. qPCR data were analyzed by the REST-MCS beta software from at least three independent experiments.",
    "ncbi_link": "HPRT: 
FoxJ1: 15223
GemC1: 239789
Geminin: 57441
McIdas: 622408"
  },
  {
    "caption": "A. and B. MTEC cultures were infected with a lentivirus expressing either GFP-GemC1 (GemC1) or GFP as a control and two days later transitioned to ALI culture conditions. Cells harvested at different time points during differentiation were co-stained with antibodies against GFP (green) to mark infected cells and endogenous McIdas(A) or Foxj1(B) (red). Arrows indicate infected cells that are McIdas or Foxj1 positive. Scale bars, 10 µm.C. and D. The percentage of infected cells expressing McIdas(C) or Foxj1(D) at each time point was quantified. Data are presented as the mean values of at least 10 independent fields obtained from at least two independent experiments for each condition. Error bars indicate ± SEM. *p<0.05, ***p<0.001. P-values were calculated by the non-parametrical two-tailed Mann-Whitney test.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "MCIDAS (A) regulatory elements (see materials and methods) cloned upstream of the luciferase gene were co-transfected into HEK293T cells with vectors expressing GemC1, McIdas and Geminin, as indicated or an empty vector (-) as a control. All luciferase experiments (A, B, D) were normalized for transfection efficiency with an expression vector for Renilla luciferase. Fold induction is the ratio between the normalized luciferase activity induced by the expression constructs and that induced by the empty expression vector. Data are the mean values of at least three independent experiments and error bars indicate ± SEM. **p<0.01, ***p<0.001. P-values were calculated by the non-parametrical two-tailed Mann-Whitney test. Abbreviations: RLF: Relative Luciferase Fold induction.",
    "ncbi_link": "luciferase: 
Renilla: 
GemC1: 239789
Geminin: 51053
MCIDAS: 622408
McIdas: 622408"
  },
  {
    "caption": "FOXJ1 (B, D) regulatory elements (see materials and methods) cloned upstream of the luciferase gene were co-transfected into HEK293T cells with vectors expressing GemC1, McIdas and Geminin, as indicated or an empty vector (-) as a control. All luciferase experiments (A, B, D) were normalized for transfection efficiency with an expression vector for Renilla luciferase. Fold induction is the ratio between the normalized luciferase activity induced by the expression constructs and that induced by the empty expression vector. Data are the mean values of at least three independent experiments and error bars indicate ± SEM. **p<0.01, ***p<0.001. P-values were calculated by the non-parametrical two-tailed Mann-Whitney test. Abbreviations: RLF: Relative Luciferase Fold induction.",
    "ncbi_link": "luciferase: 
Renilla: 
FOXJ1: 15223
GemC1: 239789
Geminin: 51053
McIdas: 622408"
  },
  {
    "caption": "McIdasmRNA levels after McIdas RNAi were assessed by qPCR (C).",
    "ncbi_link": "McIdas: 622408"
  },
  {
    "caption": "FOXJ1 (B, D) regulatory elements (see materials and methods) cloned upstream of the luciferase gene were co-transfected into HEK293T cells with vectors expressing GemC1, McIdas and Geminin, as indicated or an empty vector (-) as a control. In D, McIdas siRNAs or a control siRNA were also co-transfected. All luciferase experiments (A, B, D) were normalized for transfection efficiency with an expression vector for Renilla luciferase. Fold induction is the ratio between the normalized luciferase activity induced by the expression constructs and that induced by the empty expression vector. Data are the mean values of at least three independent experiments and error bars indicate ± SEM. **p<0.01, ***p<0.001. P-values were calculated by the non-parametrical two-tailed Mann-Whitney test. Abbreviations: RLF: Relative Luciferase Fold induction.",
    "ncbi_link": "luciferase: 
Renilla: 
FOXJ1: 15223
GemC1: 239789
McIdas: 622408"
  },
  {
    "caption": "A. and B. MCIDAS (A) and FOXJ1 (B) regulatory elements cloned upstream of the luciferase gene were co-transfected into HEK293T cells with vectors expressing GemC1, McIdas, Geminin and E2F5, as indicated, or an empty vector (-) as a control. Luciferase values were normalized against co-transfected Renilla luciferase and depicted as fold induction over the control empty vector. Data shown are mean values of at least three independent experiments and error bars indicate ± SEM. **p<0.01, ***p<0.001. P-values were calculated by the non-parametrical two-tailed Mann-Whitney test. Abbreviations: RLF: Relative Luciferase Fold induction.",
    "ncbi_link": "luciferase: 
Renilla: 
E2F5: 1875
FOXJ1: 15223
GemC1: 239789
Geminin: 51053
MCIDAS: 622408"
  },
  {
    "caption": "C. and D. Chromatin immunoprecipitation of MCIDAS and FOXJ1 promoter fragments by GemC1. HEK293T cells were co-transfected with vectors expressing GemC1-GFP (GemC1) or GFP as a control, E2F5 and DP1, together with the regulatory elements of either MCIDAS (C) or FOXJ1 (D). Following chromatin immunoprecipitation, DNA fragments of the MCIDAS and FOXJ1 promoters were detected in immunoprecipitates by qPCR. Data from a representative experiment are shown as fold enrichment of MCIDAS and FOXJ1 promoter fragments in anti-GFP immunoprecipitates over control IgG immunoprecipitates. At least two independent experiments were performed.",
    "ncbi_link": "E2F5: 1875
FOXJ1: 15223
GemC1: 239789
MCIDAS: 622408
DP1: 7027"
  },
  {
    "caption": "B. GemC1KO/KO mice compared to their wild type littermates (GemC1KO/WT) at P5.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "C. Survival plot of mice homozygous for the GemC1 deletion (GemC1KO/KO, n=8) and control wild type or heterozygous littermates GemC1 (GemC1WT, n=14). GemC1 knock-out mice exhibit markedly reduced growth after birth and die within the first postnatal week.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "A., B. Transverse sections from trachea isolated from GemC1WT/WT (upper) or GemC1KO/KO (lower) P0 mice, immunostained with antibodies against acetylated y-tubulin (ACT, cilia marker, red), pericentrin (PCNT, marker for nascent centrioles, green), γ tubulin (centriole marker, green) and E-cadherin (marker for cell boundaries, blue). Serial images have been merged to show the complete trachea section (left). Inserts show higher magnification images for acetylated y-tubulin and pericentrin staining in GemC1WT/WT and GemC1KO/KO trachea, respectively. Scale bars, 10 µm.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "C. McIdas and Foxj1 specific antibodies were used for immunofluorescence on trachea from GemC1WT/WT (upper) or GemC1KO/KO (lower) P0 mice. Arrows show representative positive cells for McIdas (green) and FoxJ1 (red) in the GemC1WT/WT mice. DNA was stained with Draq-5 (blue). Scale bars, 10 µm.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "D. Transverse sections from P0 GemC1WT/WT (upper) or GemC1KO/KO (lower) trachea, immunostained with antibodies against Keratin 5 (Krt5, basal cell marker, green), and acetylated y-tubulin (ACT, cilia marker, red). DNA was stained with Draq-5 (blue). Serial images have been merged to show the complete trachea section on the left. Higher magnification images are shown on the right. Scale bars, 10 µm.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "E. Transverse sections from P0 GemC1WT/WT (left two images) or GemC1KO/KO (right two images) trachea, immunostained with antibodies against Muc5ac (marker for mucus-expressing cells, red) and E-cadherin (marker for cell boundaries, green). DNA was stained with Draq-5 (blue). Serial images have been merged to show the complete trachea section (left). Higher magnifications from the same section are shown on the right. Scale bars, 10 µm.",
    "ncbi_link": "GemC1: 239789"
  },
  {
    "caption": "All ORFs for the sense non-AUG-dependent translation of the (G4C2)n~188, DPR coding for (GA), (GP), (GR) can be detected and quantified using a filter-trap binding assay probing for the c-terminal HA tag of the C9 DPR reporter construct. The (GA) ORF is the most abundantly detected DPR and GR the lowest in HEK293T cell 24 h post transient transfection of the C9 DPR reporter construct. n = 5.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "The C9orf72 NRE non-AUG-dependent reporter constructs recapitulate localization patterns and pathological features identified in C9orf72 NRE models. The Dendra2 (green) c-terminal fusion was used to monitor cellular localization and fluorescence intensity for each DPR translated from the G4C2 strand in HEK293T cells transiently cotransfected with an NES-mIFP-mIFP-NES (NES-mIFP) fusion protein cytoplasmic marker.",
    "ncbi_link": "Dendra2: 
mIFP: 
C9orf72: 203228"
  },
  {
    "caption": "C9 DPR reporter constructs show cell-type variability in the number of cells that are DPR positive and the overall DPR levels. Transient cotransfections of HEK293T cells robustly undergo G4C2 -Dendra2 non-AUG-dependent translation compared to NSC34 or rat primary cortical neurons. DPR positive cells and DPR fluorescent intensity were analyzed and calculated 24 h post-transfection only in cells expressing the co-transfected NES-mIFP construct. DPR fluorescent intensity was normalized to NES-mIFP fluorescent intensity to adjust for cell specific AUG-dependent translation levels; represented as fold-change relative to HEK293T. HEK293T: n = 5 with m > 500 cells analyzed per n. NSC34: n = 5 with m > 500 cells per n. Rat primary cortical neuron: n = 5 with m > 40 cells per n. (***P < 0.001, **P < 0.01, *P <0.05) See also Figure EV1-2.",
    "ncbi_link": "Dendra2: 
mIFP: "
  },
  {
    "caption": "Quantitative fluorescent microscopy imaging shows that NSC34, rat primary cortical neurons have increased relative DPR fluorescent intensity levels following compound induced cellular stress. In NES-mIFP cotransfection positive NSC34 and rat primary cortical neurons there is a significant increase in C9 DPR reporter fluorescent intensity levels 24 post treatment with most stress-inducing compounds. Fluorescent intensity was not normalized to NES-mIFP fluorescent levels. NSC34: n = 10 with m > 500 cells analyzed per n. Cortical neuron: n = 6 with m > 40 cells per n. Endogenously expression of DPRs in iPS spinal motor neurons (iPS sMN) derived from C9orf72 NRE patients increases following induction of cellular stress. DPR fluorescent intensity in iPS sMN was measured using the DPR-specific antibodies described above. IPS sMN: n = 4 with m > 20 cells per n.",
    "ncbi_link": "mIFP: 
C9orf72: 203228"
  },
  {
    "caption": "Fluorescent microscopy images shows Glutamate-induced (Glut) excitotoxic stress increases DPR levels in rat cortical neurons expressing the C9 DPR reporter and in iPS sMN derived from C9orf72 NRE patients. Glutamate-induced DPR levels are reduced by pretreating cells with the AMPA and NMDA specific antagonists NBQX and MK801, respectively. Relative fluorescent intensity quantification demonstrates there is a significant increase in DPR levels when primary cortical neurons and sMNs are challenged with the excitotoxic stressors: glutamate, AMPA, NMDA, and HC. Blocking either the AMPA or NMDA receptors reduces DPR levels in the presence of excitotoxic stressors. NES-mIFP or MAP2 were used to mark transfection positive rat cortical neurons or iPS sMNs, respectively, for quantification. DPR fluorescent intensity in iPS sMN was measured using DPR-specific antibodies. Changes in DPR levels are relative to non-stressed cells (CTRL) Cortical neuron: n = 6 with m > 40 cells per n. IPSC sMN: n = 4 with m > 25 cells per n.",
    "ncbi_link": "MAP2: 
mIFP: 
C9orf72: 203228"
  },
  {
    "caption": "Relative fluorescent intensity quantification shows a significant increase in DPR levels with increases in neuronal activity through medium and high stimulation in primary cortical neurons. No stimulation and low stimulation frequencies did not increase levels of DPR. The C9 DPR reporter, monitoring the GP DPR (ORF2), was cotransfected with ChR2. Cortical neuron: n = 4 with m > 10 cells per n. (****P < 0.0001).",
    "ncbi_link": "ChR2: 57488"
  },
  {
    "caption": "(F) and (G) Effects of thioparib on BRCA1-deficient MDA-MB-436 (F) and BRCA2-deficient Capan-1 (G) xenografts. Mice bearing MDA-MB-436 tumors were dosed orally with 10 mg/kg thioparib, 100 mg/kg olaparib, or vehicle (Veh) once daily for 3 weeks; and mice bearing Capan-1 tumors were dosed orally with 5 or 25 mg/kg thioparib, 0.3 mg/kg talazoparib, or vehicle (Veh) once daily for 3 weeks (n = 6). Data are shown as mean ± SEM. Statistical analysis was performed by two-way ANOVA. ***P < 0.0001. Representative images of xenograft tumors are shown, and mice tails represent complete regression of tumors.",
    "ncbi_link": "BRCA1: 672
BRCA2: 675"
  },
  {
    "caption": "(E) Efficacy of thioparib in the PDX model BR-05-0028 (BRCA1-deficient). Mice bearing BR-05-0028 tumors derived from a patient with breast cancer (n = 6) were treated with 10 or 30 mg/kg thioparib or 100 mg/kg olaparib for 6 weeks. Data are depicted as mean ± SEM. ***P < 0.0001.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(G) and (H). Depletion of PARP1 in HT-29 and Capan-1/TP cells resulted in a decrease in DNA damage and thioparib resistance. The upper panel shows the changes in γH2AX and phospho-RPA32 in HT-29 PARP1 knockout (KO) clones (G) or Capan-1/TP PARP1 KO clones (H) and their parental cells after exposure to thioparib for 24 h. The lower panel shows the IC50 values of thioparib in these PARP1 KO clones and parental cells. Cells were treated with thioparib for 5 or 7 d and the IC50 values were determined by SRB assay from three separate experiments. Data are presented as the mean ± SD. ThP: Thioparib, OP: Olaparib, TP: Talazoparib, 391: Cpd 391.",
    "ncbi_link": "PARP1: 142"
  },
  {
    "caption": "(A) HR repair assays in U2OS-DR-GFP cells treated with increasing concentrations of thioparib. Cells were incubated with the indicated drugs at the time of I-SceI introduction for 48 h. GFP-positive cells were analyzed after I-SceI transfection for 72 h by flow cytometry. The ATR inhibitor VE-821 was used as a positive control. Three independent experiments were performed and data are expressed as mean ± SD. Statistical analysis was performed by one-way ANOVA, and all groups were compared with control. ***P < 0.0001, *P = 0.0205, 0.0101 (from left to right).",
    "ncbi_link": "I-SceI: 854590"
  },
  {
    "caption": "(H) HR repair assay. U2OS-DR-GFP (WT) and PARP1 KO cells (KO1 and KO2) were treated with the indicated drugs for 48 h and collected after 72 h of I-SceI transfection as in (A). VE-821 served as a positive control. PARP1 knockout efficiency was evaluated by western blotting. Data from three biological replicates are presented as mean ± SD. Statistical analysis was performed by one-way ANOVA, and each group was compared with the control. ***P < 0.0001, *P = 0.0143, 0.0483, ns: P = 0.3061, 0.8269, 0.9997, 0.3906 (from left to right).",
    "ncbi_link": "PARP1: 142
I-SceI: 854590"
  },
  {
    "caption": "(C) Effects of thioparib on CXCL9, CXCL10, and IL15 mRNA in JeKo-1 cells. Data from three independent experiments are shown as the mean ± SD. Statistical analysis was performed by two-way ANOVA. Left panel: *P = 0.0367, **P = 0.0011; median panel: ***P = 0.0002, < 0.0001, < 0.0001; right panel: ***P = 0.0005, 0.0009, 0.0001 (from left to right).",
    "ncbi_link": "CXCL10: 3627
CXCL9: 4283
IL15: 3600"
  },
  {
    "caption": "(D) The protein levels of p-STAT1, p-TBK1, γH2AX, and phospho-RPA32 in HT-29 parent, PARP1−/− (#KO1), and PARP7−/− cell lines after 24 or 48 h thioparib treatment.",
    "ncbi_link": "PARP1: 142
PARP7: 25976"
  },
  {
    "caption": "(F) Western blot analysis of p-STAT1, p-TBK1, and γH2AX in HT-29 parent, STING−/−, and TBK1−/−cells after 24 or 48 h thioparib treatment.",
    "ncbi_link": "STING: 340061
TBK1: 29110"
  },
  {
    "caption": "THP-1 derived macrophages were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. Viral protein expression for PB1-F2 (A) was detected by immunoblotting at 24 h post-infection (hpi) Equal loading was confirmed by detection of beta actin.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "B THP-1 derived macrophages were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. Viral protein expression for NP (B) was detected by immunoblotting at indicated time points, respectively. Equal loading was confirmed by detection of beta actin.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(C) THP-1 derived macrophages were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. Levels of viral M1 mRNA expression were detected by RT q‑PCR at 16 hpi. The mean ± standard deviation of three independent biological samples is shown. Statistical analysis was performed by students t-test.",
    "ncbi_link": "F2: 
M1: "
  },
  {
    "caption": "(D) THP-1 derived macrophages were infected with VN and PR8 Wt and ΔF2 strains for 24 h at MOI 10. Levels of IL-1β were quantified by ELISA from the supernatants. The mean ± standard deviation of seven independent experiments is shown. Statistical analysis was performed by one-way ANOVA, p-values are indicated.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(E) THP-1 control and knockout cells for NLRP3 were mock treated or infected with the VN Wt and ΔF2 strains for 24 h at MOI 10 and IL-1β levels were assessed by ELISA from the supernatants. The mean ± standard deviation of five independent experiments is shown. Statistical analysis was performed by one-way ANOVA, p-values are indicated.",
    "ncbi_link": "F2: 
NLRP3: 114548"
  },
  {
    "caption": "(F) Immunoblot detection for NLRP3 on control and NLRP3 knockout THP-1 cells. Equal loading was confirmed by specific blotting against beta actin. Representative blot of three independent repeats is shown.",
    "ncbi_link": "beta actin: 
NLRP3: 114548"
  },
  {
    "caption": "(G) Human primary macrophages differentiated from PBMCs from two healthy donors were infected with H5N1 Wt and ΔF2 for 5 h at MOI 10. Levels of IL-1β were measured by ELISA in technical replicates. The mean of two independent experiments is shown. Statistical analysis was performed by one-way ANOVA, p-values are indicated.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(H) THP-1 derived macrophages were infected with a human H3N2 IAV strain (Wyo) Wt and ΔF2 for 24 h at MOI 4. Levels of IL-1β were measured by ELISA from the supernatants. The mean ± standard deviation of four independent experiments is shown. Statistical analysis was performed by one-way ANOVA, p-values are indicated.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(I) Detection of viral matrix protein M1 by immunoblotting in cells infected with the H3N2 Wt and ΔF2 strains.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(J) Human primary macrophages isolated and differentiated from PBMCs from three healthy donors were infected with H3N2 Wt and ΔF2 for 24 h at MOI 4. Levels of IL-1β were measured by ELISA. The mean ± standard deviation of three independent experiments is shown. Statistical analysis was performed by one-way ANOVA, p-values are indicated.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "Primary human alveolar macrophages from BALF of five pediatric patients (patients are color coded) were infected with the human H3N2 strain (Wyo) Wt and ΔF2 for 16 h at MOI 1. (K) Levels of IL-1β were measured by ELISA from the supernatants. The mean ± standard deviation is shown.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "Primary human alveolar macrophages from BALF of five pediatric patients (patients are color coded) were infected with the human H3N2 strain (Wyo) Wt and ΔF2 for 16 h at MOI 1. Levels of viral M1 mRNA (L), Mx1 mRNA (M) and IP10 mRNA (N) expression were detected by RT q‑PCR. The mean ± standard deviation for cells from four patients are shown. Individiual patients are color coded.",
    "ncbi_link": "F2: 
M1: 
IP10: 3627
Mx1: 4599"
  },
  {
    "caption": "(A-D) THP-1 cells were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. Flow cytometry results for annexin V single positive (A and C) and annexin V and zombie dye double positive (B and D) cells. Percentage of positive cells are depicted at 12 hpi or 24hpi.",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(E and F) THP-1 cells were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. LDH release measured from supernatants of mock treated or infected cells at 12 hpi (E) or 24hpi (F).",
    "ncbi_link": "F2: "
  },
  {
    "caption": "G THP-1 Caspase 1 -/- cells were infected with the wildtype (Wt) and ΔF2 H5N1 (VN) virus at MOI 10. LDH release measured from supernatants of mock treated or infected cells at 12 hpi or 24hpi. n=3 for 12hpi, n=5 for 24hpi. Medians are indicated, statistical analysis was performed by one-way ANOVA.",
    "ncbi_link": "F2: 
Caspase 1: 834"
  },
  {
    "caption": "(A) THP-1 cells infected with VN Wt and ΔF2 virus at a MOI 10 for 24 h or treated with 6.7 μM of nigericin (nig) for 45 min were analyzed by immunoblotting. Detection of the full-length gasdermin D. Equal loading was confirmed by beta actin. One representative blot of five independent repeats is shown. (B) Quantification of band intensity for the gasdermin D full-length isoform. The mean ± standard deviation five independent experiments is shown. Statistical analysis was performed by the paired two‑tailed Student's t test., The asterisk (*) marks a significant difference when compared to the mock group ** p < 0.01. ",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(C) THP-1 cells infected with VN Wt and ΔF2 virus at a MOI 10 for 24 h or treated with 6.7 μM of nigericin (nig) for 45 min were analyzed by immunoblotting. Detection of cleaved gasdermin D N-terminal and C-terminal isoforms by immunoblot in supernatants; one representative experiment of three independent repeats is shown. (D) Quantification of band intensity for N-terminal gasdermin D isoform band. Three independent experiments are shown. Statistical analysis was performed by the paired two‑tailed Student's t test., * p < 0.05. (E) Quantification of band intensity for C-terminal gasdermin D isoform band. Three independent experiments are shown. Statistical analysis was performed by the paired two‑tailed Student's t test., * p < 0.05. ",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(F) THP-1 cells infected with VN Wt and ΔF2 virus at a MOI 10 for 24 h or treated with 6.7 μM of nigericin (nig) for 45 min were analyzed by immunoblotting. Pro-caspase-1 and active caspase-1 were detected by immunoblot in cell lysates (cell, upper panels) and supernatants (sup, lower panels) from the same experiment. One representative experiment of three independent repeats is shown. (G) Quantification of band intensity for active caspase-1 band. Five independent experiments are shown. Statistical analysis was performed by the paired two‑tailed Student's t test. * p < 0.05. (H) Levels of total pro-caspase-1 were quantified on pellets and respective supernatants. Three independent experiments are shown. Statistical analysis was performed by the paired two‑tailed Student's t test. ",
    "ncbi_link": "F2: "
  },
  {
    "caption": "(A) Western blot analysis of whole cell lysate (input) and Flag-specific immunoprecipitation (IP) from 293T cells co-transfected with expression plasmids encoding V5-NLRP3 and Flag ZsGreen-PB1-F2 from indicated viral strains for 24 h Representative blot of three independent repeats is shown. (B) Quantification of the NLRP3 IP band was normalized to the respective NLRP3 input band (n=3 independent biological replicates, normalized to the respective input). Mean values +- SD are indicated. ",
    "ncbi_link": "Flag: 
PB1-F2: 
V5: 
ZsGreen: 
NLRP3: 114548"
  },
  {
    "caption": "(E) 293T cells co transfected with expression plasmids encoding different truncation mutants for Flag Zsgreen-PB1-F2 from VN (H5N1) and V5-NLRP3 were processed as described in (A). Representative blot of three independent repeats is shown.",
    "ncbi_link": "Flag: 
PB1-F2: 
V5: 
Zsgreen: 
NLRP3: 114548"
  },
  {
    "caption": "(B) 293T cells were co-transfected with expression plasmids encoding for the indicated V5-tagged domains of NLRP3 for 24h. Whole cell lysate (left blot) and flag specific IP (right blot) were analyzed by immunoblotting. Equal loading was confirmed by blotting against tubulin. Representative blots of two independent experiments are shown.",
    "ncbi_link": "flag: 
V5: 
NLRP3: 114548"
  },
  {
    "caption": "(C) 293T cells were co‑transfected with expression plasmids encoding Flag-NLRP3, V5‑PB1-F2 and V5‑ASC for 24h. Whole cell lysate and flag specific IP were analyzed by immunoblotting for indicated antigens. Equal loading of whole cell lysate was assured by blotting against beta actin. Representative blot of two independent repeats is shown.",
    "ncbi_link": "Flag: 
PB1-F2: 
V5: 
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "(D) 293T cells were co-transfected with expression plasmids encoding for Flag-NLRP3, PB1-F2 or NEK7 or combinations thereof as indicated. Whole cell lysate and Flag IP were analyzed by immunoblotting. Equal loading was confirmed by blotting against beta actin. Representative blots of three independent experiments are shown. Right panel: Quantification of IP bands' intensity relative to their input. The mean ± standard deviation of three independent experiments is shown. Statistical analysis was performed by paired two‑tailed Student's t test (*p< 0.05).",
    "ncbi_link": "Flag: 
PB1-F2: 
NEK7: 140609
NLRP3: 114548"
  },
  {
    "caption": "(E) As in D: 293T cells were co-transfected with expression plasmids encoding for Flag-NLRP3-LRR, PB1-F2 or NEK7 or combinations thereof as indicated. Whole cell lysate and NLRP3-LRR IP were analyzed by immunoblotting. Equal loading was confirmed by blotting against beta actin. Representative blots of three independent experiments are shown. (F) Quantification of IP bands' intensity relative to their input. The mean ± standard deviation of three independent experiments is shown. Statistical analysis was performed by paired two‑tailed Student's t test (*p< 0.05). ",
    "ncbi_link": "Flag: 
PB1-F2: 
NEK7: 140609
NLRP3: 114548"
  },
  {
    "caption": "G) As in D and E: 293T cells were co-transfected with expression plasmids encoding for Flag-NLRP3-LRR, PB1-F2 or V5-NLRP3-Pyrin or combinations thereof as indicated. Whole cell lysate and NLRP3-LRR IP were analyzed by immunoblotting. Equal loading was confirmed by blotting against tubulin. Representative blots of three independent experiments are shown.",
    "ncbi_link": "Flag: 
PB1-F2: 
V5: 
NLRP3: 114548"
  },
  {
    "caption": "Colony formation assay of miRNA mimic transfected-Dgcr8-/- ESCs. There were 17 miRNAs that decreased the colony forming ability, 15 miRNAs that did not affect colony formation and 8 miRNAs enhanced colony formation of ESCs. Representative pictures are shown. Full data are shown in Supplementary Fig S1.",
    "ncbi_link": "Dgcr8: 94223"
  },
  {
    "caption": "Cell cycle distribution in representative miRNAs evoking G1 phase accumulation in miRNA mimic transfected Dgcr8-/- ESCs. Error bars indicate s. d. (n=3). Full data are shown in Supplementary Fig S3A, B.",
    "ncbi_link": "Dgcr8: 94223"
  },
  {
    "caption": "B,C. Northern blot analysis of the expression of miR-23a, miR-27a and miR-24 during EB formation (B) and RA induced differentiation of V6.5 ESCs (C). The heatmap was representive of the results of quantitative analysis.",
    "ncbi_link": "miR-23a: RF00642
miR-24: RF00178
miR-27a: 407018///RF00644"
  },
  {
    "caption": "D,E. The expression of primary miR-23a~27a~24-2 transcript during EB formation (D) and RA induced differentiation (E). Error bars indicate s.d. (n=3).",
    "ncbi_link": "miR-23a: RF00642"
  },
  {
    "caption": "D,E. The expression of primary miR-23a~27a~24-2 transcript during EB formation (D) and RA induced differentiation (E). Error bars indicate s.d. (n=3).",
    "ncbi_link": "miR-23a: 387216"
  },
  {
    "caption": "F. Q-PCR analysis of miR-23a, miR-27a and miR-24 expression in ESCs (JM8A3) and a variety of C57BL/6J adult tissues. Data are shown as mean + s.d. (n=3).",
    "ncbi_link": "miR-23a: RF00642
miR-24: RF00178
miR-27a: RF00644"
  },
  {
    "caption": "G. Relative protein levels of Oct4, Sox2 and Nanog in miRNA mimic transfected Dgcr8-/- ESCs and wild- type ESCs.",
    "ncbi_link": "Dgcr8: 94223"
  },
  {
    "caption": "H,I. Oct4, Nanog, Foxa2, Gata2 and Nestin immunofluorescence staining of mimic transfected Dgcr8-/- (H) and wild- type ESCs(I).",
    "ncbi_link": "Dgcr8: 94223"
  },
  {
    "caption": "Western blot analysis of the expression of target genes in miR-27a or miR-24 over-expressed V6.5 ESCs. Candidate target genes whose expression was decreased were framed.",
    "ncbi_link": "miR-24: RF00178
miR-27a: RF00644"
  },
  {
    "caption": "The relative luciferase activity of the reporter constructs co-transfected with scramble or miR-27a and miR-24 mimics. Error bars indicate s.d. (n=3); * indicates P-value < 0.05. Candidate target genes whose luciferase activity was decreased were framed. PC group was positive reporter control which harbored reverse complementary sequence of miR-27a or miR-24.",
    "ncbi_link": "miR-24: RF00178
miR-27a: 407018"
  },
  {
    "caption": "The relative luciferase activity of the wild-type 3′ UTR or mutated 3′ UTR reporter co-transfected with scramble or miR-27a and miR-24 mimics. Data are shown as mean + s.d. (n=3); * indicates P-value < 0.05.",
    "ncbi_link": "miR-24: RF00178
miR-27a: 407018"
  },
  {
    "caption": "I. Q-PCR analysis of primary-23a~27a~24-2, miR-23a, miR-27a and miR-24 expression in c-Myc knocked down ESCs. Error bars indicate s.d. (n=3); * indicates P-value < 0.05; ** indicates P-value < 0.01; *** indicates P-value < 0.001.",
    "ncbi_link": "miR-23a: RF00642
miR-24: RF00178
miR-27a: RF00644
c-Myc: 17869"
  },
  {
    "caption": "L. Relative luciferase activity of the wild-type and -15 binding site mutated promoter in NIH3T3 cells co-transfected with c-Myc or the blank vector (NC). Error bars indicate s.d. (n=3); * indicates P-value < 0.05.",
    "ncbi_link": "c-Myc: 17869"
  },
  {
    "caption": "AP staining of the iPSC colonies in reprogramming with OSK combined with scramble control, inhibitors of miR-23a, miR-27a, miR-24 and let-7c respectively.",
    "ncbi_link": "let-7c: RF00027
miR-23a: RF00642
miR-24: RF00178
miR-27a: RF00644"
  },
  {
    "caption": "Detection of endogenous and exogenous Oct4, Sox2, Klf4 and Nanog expression in iPSCs, ESCs and MEFs by RT-PCR.",
    "ncbi_link": "Klf4: 16600
Nanog: 71950
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "Q-PCR analysis of the expression of self-renewal (Oct4, Sox2, Nanog) and differentiation (Cdx2, Foxa2, Brachyury, Hand1, Nestin, FGF5) relative markers in EBs derived from the iPSCs. Error bars indicate s.d. (n=3).",
    "ncbi_link": "Cdx2: 12591
FGF5: 14176
Foxa2: 15376
Hand1: 15110
Nanog: 71950
Nestin: 18008
Oct4: 18999
Sox2: 20674
Brachyury: 20997"
  },
  {
    "caption": "Genomic PCR of the specific fragments spanning miR-23~27~24 clusters. WT indicate wild-type ESCs; DKO indicate miR-23a~27a~24-2-/-, miR-23b~27b~24-1-/- ESCs; KO indicate miR-23a~27a~24-2-/- ESCs.",
    "ncbi_link": "miR-23a: RF00642"
  },
  {
    "caption": "Real-time PCR analysis of mature miR-23a/b, miR-27a/b and miR-24 expression in wild-type, DKO and KO ESCs. Data are shown as mean + s.d. (n=3).",
    "ncbi_link": "miR-23a: RF00642
miR-24: RF00178
miR-27a: RF00644"
  },
  {
    "caption": "Real-time PCR analysis of Oct4, Sox2 and Nanog expression in wild-type and miR-23~27~24 cluster knockout ESCs. Data are shown as mean + s.d. (n=3).",
    "ncbi_link": "Nanog: 71950
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "Real-time PCR analysis of Oct4 and several lineage differentiation markers expression during EB formation of wild-type and knockout ESCs. Data are shown as mean ± s.d. (n=3).",
    "ncbi_link": "Oct4: 18999"
  },
  {
    "caption": "A The mRNA expression of FAM189A2/ENTREP in the primary human mammary epithelium HMEC and human breast cancer  cell lines. In  qRT-PCR analyses, the  expression was normalized to the immortalized normal human mammary epithelium HMEC4tertshp16. Relative expression ratios shown as mean + SD from three biological replicates.",
    "ncbi_link": "ENTREP: 9413
FAM189A2: 9413"
  },
  {
    "caption": "B Relative expression of FAM189A2/ENTREP in the normal (white) and cancer (green) tissues of breast (Curtis  Breast), lung (Okayama Lung), colorectal (TCGA Colorectal) and  head  and neck (Estilo Head-Neck). Data were downloaded from the Oncomine database P-values obtained by Student's t-tests and the number of cases are listed on the top and bottom of figures, respectively. P < 0.05 was considered as statistically significant. Box-whisker plot represents the interquartile range (25th and 75th percentiles) as a box and the median as a line. The maximn and minimun values within 1.5 x interquartile range are shown as whiskers. Outlier data are plotted as dots. C Relative  expression of FAM189A2/ENTREP in the primary (green) and the metastatic sites (blue) including lymph node, bone, liver,  lung, soft tissues of prostatic cancer (Grasso  Prostate) (left) and in the normal (white), primary (green) and metastatic sites (three cases of sentinel lymph node) (blue) of breast cancer (TCGA Breast) (right). Note that only three cases of the  metastatic breast cancer were available in the dataset. Data were downloaded from the Oncomine database P-values obtained by Student's t-tests and the number of cases are listed on the top and bottom of figures, respectively. P < 0.05 was considered as statistically significant. Box-whisker plot represents the interquartile range (25th and 75th percentiles) as a box and the median as a line. The maximn and minimun values within 1.5 x interquartile range are shown as whiskers. Outlier data are plotted as dots.",
    "ncbi_link": "ENTREP: 9413
FAM189A2: 9413"
  },
  {
    "caption": "B, C The immunoprecipitation analysis. Co-precipitation was impaired by either the WW domain deletion of ITCH or the mutation in the PPxY motifs of ENTREP. Data shown are representative of at least two independent experiments. IP, immunoprecipitation; IB, immunoblot.",
    "ncbi_link": "ENTREP: 9413
ITCH: 83737"
  },
  {
    "caption": "A The  nickel-pull down assay using  myc/HIS-tagged ENTREP along with HA-tagged ubiquitin. Arrows indicate  HA-ubiquitin-incorporating ENTREP. Arrowhead indicates ENTREP without ubiquitination. Data shown are representative of three independent experiments.",
    "ncbi_link": "HA: 
HIS: 
myc: 
ENTREP: 9413"
  },
  {
    "caption": "A The  immunoprecipitation  analysis. The cytoplasmic ENTREP (wild or mut1+2 mutant)  co-precipitated with EPN1myc in the presence of ITCH wild or C830A. The  blot  bands were semi-quantified using ImageJ software. ENTREP ratio was caluculated as a ratio of  ENTREP  in the myc-coprecipitaed sample to that of the total lysate. The ratios shown as mean ± SD from three biological replicates. P-values were obtained by Student's t-tests and P < 0.005 was considered as statistically significant. No significant difference was observed.",
    "ncbi_link": "ITCH: 83737"
  },
  {
    "caption": "F The nickel-pull down assay using indicated vectors along with HISx6-tagged wild type ubiquitin vector. HA-tagged DsRed was used as a control for HA-CXCR4DD-DsRed. Arrowhead,  FLAG-tagged ITCH (wild or C830A); arrow, FLAG-ENTREP  wild cyt. Data shown are representative of at least two independent experiments. G Co-localization of ENTREP  and CXCR4 in the  endosome.  Cos7  cells were transfected with ENTREP-FLAG, CXCR4-DsRed and Halo-ITCH wild vectors and treated with  CXCL12. ENTREP-FLAG and CXCR4-DsRed co-localized in the RAB7-positive  endosome. Inserts, the high-magnification images of the marked area indicating the  colocalizaion of ENTREP-FLAG, CXCR4-DsRed and RAB7. Scale bar 10mm. The image is representative of at least two independent experiments.",
    "ncbi_link": "DsRed: 
FLAG: 
HA: 
Halo: 
HIS: 
CXCR4: 7852
ENTREP: 9413
ITCH: 83737"
  },
  {
    "caption": "C The expression of endogenous CXCR4  in  lentivirally-transduced MCF-7 ENTREP-KO cells. CXCL12 (+) and (-) indicate the presence and absence of CXCL12  treatment. In CXCL12-treated ENTREP-EGFP expressing cells, a non-negligible amount of CXCR4 was observed in the  cytoplasm, in which CXCR4 was overlapped with ENTREP-EGFP. CXCR4 expression on the cell surface still remained (arrows). Scale bar 10 mm. The images are representative of at least three independet experiments.",
    "ncbi_link": "EGFP: 
ENTREP: 9413"
  },
  {
    "caption": "A Dot plot presentation of the chemotaxis  analyses using the Boyden chamber. CXCL12 (+) and (-) indicate the presence and absence of CXCL12  as an attractant in the bottom chambers. ENTREP-knockout enhanced the chemotaxis toward CXCL12, which was blocked by pre-treatment with AMD3100 (upper panel). The doxycyclin (DOX)-induced  ENTREP expression suppressed the chemotaxis  of mouse 4T1-Luc  cells toward  CXCL12 (lower panel). Ratio of  migrated cells into the bottom chamber against the applied cells on the top chambers was normalized by the results of non-treated cells (n=7, upper panel, and n=9, lower panel, from at least two independent experiments, respectively). P-values were obtained by Student's t-tests and P < 0.005 was considered as statistically significant. Insert, the  immunoblot  analysis of the DOX-induced ENTREP expression in 4T1-Luc cells. NS, not significant.",
    "ncbi_link": "ENTREP: 9413
ENTREP: 381217"
  },
  {
    "caption": "(B) Body weight comparison over time of Ndufs3 smKO male mice (filled blue squares; n=14) and age matched wild-type (WTFlx; n=15) males (empty blue squares). Ndufs3 smKO females (filled red circles) showed similar results (n=10 for smKO, and n=12 for WTFlx group). P values were calculated by Student's t test;",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(C) Representative image of a smKO male Ndfu3s3-smKO mouse and a WTFlx littermate of 6-month old showing decreased body weight.",
    "ncbi_link": "Ndfu3s3: 68349"
  },
  {
    "caption": "(D) Survival curve of Ndufs3 smKO female mice (red line) and males (blue line). P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0010 for males (n=19), and p=0.0004 for females (n=10).",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(E) Nocturnal ambulatory activity of Ndufs3 smKO and aged matched wild-type littermates from 1 and 2 months old male mice. P values were calculated by Student's t test. P values were calculated by Student's t test to determine the level of statistical difference. ; *p<0.05, **p<0.01 and ***p<0.0001.",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(F) The number of falls in the treadmill of WTFlx and Ndufs3 smKO male mice, starting at 2 months (n=8). Bars represent means ± standard error (SE). P values were calculated by Student's t test to determine the level of statistical difference. n.s.-not significant; *p<0.05, **p<0.01 and ***p<0.0001.",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(G) Rotarod performed by Ndufs3 smKO and wild-type male mice. (n=8). Bars represent means ± standard error (SE). P values were calculated by Student's t test to determine the level of statistical difference. n.s.-not significant; *p<0.05, **p<0.01 and ***p<0.0001.",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(A) Representative image of quadriceps from WTFlx and Ndufs3 smKO animals of 8 months of age. Muscle weight from Ndufs3 smKO males (black bar) and wild-type mice (white bar) from 6, and 8 months of age (n=5 each group). Bars represent means ± standard error (SEM).",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(B) Representative H&E, COX, and SDH staining of quadriceps from WTFlx and Ndufs3-Mlc1f smKO at 8 months old.",
    "ncbi_link": "Mlc1f: 17901
Ndufs3: 68349"
  },
  {
    "caption": "(C) Cross-sectional area (CSA) of quadriceps muscle fibers. A minimum of 100 fibers/sample were analyzed (n =3/genotype). The percentage of central nuclei in skeletal muscle fibers of quadriceps muscle of WTFlx and Ndufs3 smKO at 8 months (n =3 mice for WTFlx and n=4 mice for Ndufs3 smKO). P values were calculated by Student's t test.",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(D) Serum lactate levels of WTFlx and Ndufs3-smKO animals at different ages. Ndufs3 smKO male mice (filled black squares) showed increased levels compared to matched WTFlx males (empty black squares). Error bars represent SEM.",
    "ncbi_link": "Ndufs3: 68349"
  },
  {
    "caption": "(E) BN-PAGE In-Gel Activities of Complex I and IV measured in homogenates from quadriceps of wild-type and Ndufs3-Mlc1f smKO animals at 2 and 4 months.",
    "ncbi_link": "Mlc1f: 17901
Ndufs3: 68349"
  },
  {
    "caption": "(F-G) Western blots of muscle homogenates (quadriceps) of WTFlx and Ndufs3-Mlc1f smKO animals at different ages (2 and 4 months, respectively) using antibodies against PGC-1α, COX1 (complex IV subunit), NDUFS3, VDAC1, SDHA (complex II subunit), and β-actin. (H) Quantification of the western blots in panels F and G. Bars represent means ±SEM of n=4 for each group. P values were determined by Student's t test.",
    "ncbi_link": "Mlc1f: 17901
Ndufs3: 68349"
  },
  {
    "caption": "(C) The KO-GFP mouse was visibly smaller and weaker than a KO-NDUFS3 mouse, at 7 months.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(D) Females body weight injected with rAAV9-Ndufs3 (heretofore referred to as KO-NDUFS3) mice were similar to WTFlx mice body weight and significantly higher than the rAAV9-eGFP injected mice (KO-GFP) starting at 5 months. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0016 (KO-NDUFS3 vs KO-GFP); p=0.0014 (KO-GFP vs WTFlx); n-indicates the number of animals used per group.",
    "ncbi_link": "eGFP: 
GFP: 
Ndufs3: 68349
NDUFS3: 68349"
  },
  {
    "caption": "(E) Males body weight of KO-NDUFS3 mice were similar to WTFlx mice, and significantly different from KO-GFP from 4 months onwards. Statistical analysis was performed by One-way ANOVA followed by a Tukey post-test. P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0016 (KO-NDUFS3 vs KO-GFP); p=0.0014 (KO-GFP vs WTFlx); n-indicates the number of animals used per group.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(F) Treadmill performance was significantly improved in the KO-NDUFS3 mice when compared to the KO-GFP, from 2 months onwards. P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0016 (KO-NDUFS3 vs KO-GFP); p=0.0014 (KO-GFP vs WTFlx); n-indicates the number of animals used per group.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(G) Four limb strength was evaluated by the grid hang test. KO-NDUFS3 mice performed significantly better starting at 3 months, when compared to the KO-GFP mice. F) and G) Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test. P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0016 (KO-NDUFS3 vs KO-GFP); p=0.0014 (KO-GFP vs WTFlx); n-indicates the number of animals used per group.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(H) Quadriceps and gastrocnemius wet weight of 6 months old mice was similar between WTFlx and KO-NDUFS3 mice. Quadriceps weight was significantly increased in KO-NDUFS3 mice when compared to KO-GFP injected. Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test. ns- not significant. P values were calculated using Log-rank (Mantel-Cox) Test; p=0.0016 (KO-NDUFS3 vs KO-GFP); p=0.0014 (KO-GFP vs WTFlx); n-indicates the number of animals used per group.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(I) Survival curve of Ndufs3 smKO mice injected with rAVV9-Ndufs3 (blue line) and with rAVV9-eGFP (green line). WTFlx mice are depicted in black. rAAV9-Ndufs3 injections extended the survival of the smKO mice.",
    "ncbi_link": "eGFP: 
Ndufs3: 68349"
  },
  {
    "caption": "(A) Western blots of 6 months old quadriceps of WTFlx, KO and KO-NDUFS3 injected mice at 15-18 days old. GFP expression was observed only in the KO-GFP mice. Protein loading was obtained with stain-free gel technology. (B) Quantification of NDUFS3, COXI and SDHA expression levels in female mice showed in A.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(G) Total mtDNA levels in quadriceps from males and females were determined by qPCR using the ratio ND1/18S. Inset shows the appearance of the quadriceps, reflecting normalization of mitochondrial levels after replacement of NDUFS3.",
    "ncbi_link": "ND1: 17716
NDUFS3: 68349
18S: 100861531"
  },
  {
    "caption": "(B) The smKO mice group that received retro-orbital injections at 2 months was tested prior to the rAAV9-Ndufs3 injection showing a significant exercise intolerance attested by the number of falls in the treadmill. The KO-NDUFS3 gradually recovered over time. Individual KO-NDUFS3 mice are color coded. Green triangles represent the animals injected with GFP whereas white triangles represent non-injected mice. Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test.",
    "ncbi_link": "GFP: 
Ndufs3: 68349
NDUFS3: 68349"
  },
  {
    "caption": "(C) The hang test was performed in symptomatic mice which had a significant decrease in four-limb muscle strength and coordination, at 2 months. The KO-NDUFS3 mice showed a significant recovery 3.5 months after injection. Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test.",
    "ncbi_link": "NDUFS3: 68349"
  },
  {
    "caption": "(D) KO-NDUFS3 muscle weight was similar to WTFlx mice, and it was significantly increased in gastrocnemius when compared to KO-GFP mice. Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(E) Immunohistochemical analysis with NDUFB8 and COX1 antibodies in quadriceps muscle sections of 6-month-old animals. The expression of NDUFB8 (representative of assembled CI) was recovered in the KO-NDUFS3 mice and COX1 expression was similar to WTFlx animals.",
    "ncbi_link": "NDUFS3: 68349"
  },
  {
    "caption": "(F) COX and COX/SDH activity staining showed that KO-NDUFS3 quadriceps were reverted to levels found in wild-type, at 6 months. n-indicates the number of animals used per group, scale: 100 µm.",
    "ncbi_link": "NDUFS3: 68349"
  },
  {
    "caption": "(A) Western blots showed NDUFS3 expression in KO-NDUFS3 and GFP expression in the KO-GFP quadriceps samples. PGC-1α expression was normalized in the KO-NDUFS3 mice which was abnormally elevated in the KO-GFP. The same was observed for CIV (COX1), CIII (Core 2) and CII (SDHA). (B) Quantification of western blots showed in A. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. Data represent means ±SEM.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(C) BN-PAGE western blots showed recovery of Complex I assembly into complex and supercomplexes in KO-NDUFS3 injected mice. CIV and CII were similar to wild-type in the KO-NDUFS3 samples, at 6 months.",
    "ncbi_link": "NDUFS3: 68349"
  },
  {
    "caption": "(E) BN-PAGE In-gel CI and IV activities of KO-NDUFS3 mice were also reverted to levels similar to the WTFlx samples (F) Quantification of in-gel activities. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. Data represent means ±SEM.",
    "ncbi_link": "NDUFS3: 68349"
  },
  {
    "caption": "(G) Complex I/Citrate synthase activity of KO-NDUFS3 samples measured spectrophotometrically were similar to WTFlx samples and increased in comparison to KO-GFP mice. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. Data represent means ±SEM.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(H) Total mtDNA levels were determined by qPCR. MtDNA levels in KO-NDUFS3 mice were decreased when compared to KO-GFP mice and not different from the levels in WTFlx mice. Statistical analysis was performed by One-way ANOVA followed by Bonferroni post-test. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. Data represent means ±SEM.",
    "ncbi_link": "GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(I) The serum lactate levels were similar to WTFlx in KO-NDUFS3 samples and significantly decreased when compared to KO-GFP levels. The individual KO-NDUFS3 animals are color coded. Green triangles represent the animals injected with rAAV9-eGFP whereas black triangles represent animals which did not receive an rAAV9-eGFP injection. Statistical analysis was performed by One-way ANOVA followed by Tukey post-test. Data represent means ±SEM.",
    "ncbi_link": "eGFP: 
GFP: 
NDUFS3: 68349"
  },
  {
    "caption": "(E), Kaplan-Meier  analysis of  survival  rates in WT,  Fpr1 and Fpr2  KO mice after i.p. challenge with 2x105 bacteria. Data are the cumulative results from two experiments, each involving 8 animals per group. **P < 0.01, ****P < 0.0001 vs WT mice, as determined by Kaplan-Meier analysis. Data information: means + SDs of three duplicate determinations, each conducted in a different animal.",
    "ncbi_link": "Fpr1: 14293
Fpr2: 14289"
  },
  {
    "caption": "(F-G)  Neutrophil  influx (F) and  bacterial burden (G) in peritoneal lavage fluid samples collected from Fpr2-/- mice at 3 h after i.p. challenge with live GBS (2x107 CFU). At 1h post-challenge mice were inoculated i.p. with 1 μg of recombinant Cxcl1   or Cxcl2  or with vehicle. Data information: , individual data points and means. *P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle treated mice determined by unpaired t test or Mann-Whitney U test",
    "ncbi_link": "Fpr2: 14289"
  },
  {
    "caption": "(D), Effect of the absence of  Fpr1, Fpr2 or the TLR adaptor MyD88  on the activation of AP-1 family members in  neutrophils. Neutrophils from WT, Fpr- or  MyD88-deficient mice  were stimulated for 90 min with live GBS (MOI 5), lysed and assayed for AP-1 activation. Data are means + SD from three independent experiments conducted in duplicate. *P < 0.05, ***P < 0.001 vs WT  mice, as determined by unpaired t-test.",
    "ncbi_link": "Fpr1: 14293
Fpr2: 14289
MyD88: 17874
TLR: 21897///24088///142980///21898///53791///21899///170743///170744///81897///239081///384059///279572"
  },
  {
    "caption": "(F), Effect of the absence of Fpr1,  Fpr2  or the  TLR  adaptor MyD88  on  p38MAPK activation in neutrophils  stimulated with live  GBS  (MOI 5). Shown is a blot representative of three separate experiments.",
    "ncbi_link": "Fpr1: 14293
Fpr2: 14289
MyD88: 17874"
  },
  {
    "caption": " F. A physical 650-kb window of the genomic distribution of genes surrounding SNP rs4971059, such as EFNA4, KRTCAP2, MUC1, MIR92B, THBS3,and DAP3 (top). Total RNAs were extracted from [GG], [GA], or [AA] MCF-10A cells and analyzed for the expression of EFNA4, KRTCAP2, TRIM46, MUC1, THBS3, MIR92B, or DAP3 by RT-qPCR. TRIM28 was examined as a negative control (bottom). ",
    "ncbi_link": "DAP3: 7818
EFNA4: 1945
KRTCAP2: 200185
MIR92B: 693235
MUC1: 4582
THBS3: 7059
TRIM28: 10155
TRIM46: 80128"
  },
  {
    "caption": " B. MCF-7 cells were transfected with a control vector or FLAG-TRIM46 for 40 h and treated with DMSO or MG132 (2μM) for 10h. Cellular lysates were then collected for western blotting with antibodies against the indicated proteins. ",
    "ncbi_link": "FLAG: 
TRIM46: 80128"
  },
  {
    "caption": " F. Schematic diagrams of HDAC1 deletion mutants. GST pull-down experiments were performed with bacterially expressed GST-fused proteins as indicated and in vitro transcribed/translated TRIM46. ",
    "ncbi_link": "HDAC1: 3065"
  },
  {
    "caption": " F. MCF-7 cells were transfected with empty vector or FLAG-TRIM46 for forty-eight hours and then treated with 50 μg/mL cycloheximide (CHX) for the indicated hours. DMSO was added to cells 10 h before cellular proteins were collected for western blotting (left). On the right panel, quantitation was done by densitometry analysis of the immunoblots and expressed as signals of HDAC1. G. MCF-7 cells were treated as described in F, except that MG132 (10 μM) was added to cells 10 h before cellular proteins were collected for western blotting (left). Quantitation was performed on the right panel as in F. H. MCF-7 cells were treated with control siRNA or TRIM46 siRNA. Forty-eight hours after transfection, cells were treated with 50 μg/mL CHX for the indicated hours before cellular proteins were extracted for western blotting analysis (left). Quantitation was performed on the right panel as in F. ",
    "ncbi_link": "TRIM46: 80128"
  },
  {
    "caption": "  In vivo ubiquitination assays performed in MCF-7 cells. (B) Stable shCTR- or shTRIM46-expressing MCF7 cells were transfected with His-Ub for 40 h. Cells were then treated with MG132 (10 μM) for 12 h before Ni-NTA bead precipitation followed by IB with anti-HDAC1. ",
    "ncbi_link": "TRIM46: 80128"
  },
  {
    "caption": " E-G. Verification of representative genes targeted by the TRIM46-HDAC1 axis. (E) MCF-7 cells were transfected with empty vector, FLAG-TRIM46, or FLAG-TRIM46 together with FLAG-HDAC1 for 48 h. (F) MCF-7 cells were transfected with control siRNA, TRIM46 siRNA, or TRIM46 siRNA together with HDAC1 siRNA for 72 h. (G) MCF-7 cells were transfected with control siRNA, TRIM46 siRNA, or a siRNA-resistant TRIM46 construct together with TRIM46 siRNA for 72 h. Total RNAs were extracted from cells and RT-qPCR was performed with primers specific for indicted genes. ",
    "ncbi_link": "FLAG: 
HDAC1: 3065
TRIM46: 80128"
  },
  {
    "caption": " B. EdU assays were performed in MCF-7 cells treated with control siRNA, TRIM46 siRNA or TRIM46 siRNA and HDAC1 siRNA for 72 h, or MCF-10A cells treated with vector, FLAG-TRIM46 or FLAG-TRIM46 and FLAG-HDAC1 for 48 h. Representative images from FACS analysis are shown on the left panel, the percentage numbers of cells in S phase was quantified by FlowJo software on the right panel. ",
    "ncbi_link": "FLAG: 
HDAC1: 3065
TRIM46: 80128"
  },
  {
    "caption": " G. Accumulation of γH2AX in cells depleted of TRIM46 or HDAC1 after cisplatin stimulation. MCF-7 cells were treated with 4 μM cisplatin for 8 h before harvesting. Cell lysates were analyzed by western blotting. ",
    "ncbi_link": "HDAC1: 3065
TRIM46: 80128"
  },
  {
    "caption": "D. Control MCF-7 cells or MCF-7 cells depleted with TRIM46 were treated with different concentrations of cisplatin (cis), VP16, or adriamycin (ADM) for 72 h, and the proportions of viable cells were examined. E. Control MCF-10A cells or MCF-10A cells overexpressed TRIM46 were treated with different concentrations of cisplatin, VP16, or adriamycin for 72 h, and the proportions of viable cells were examined.",
    "ncbi_link": "TRIM46: 80128"
  },
  {
    "caption": " E. Kaplan-Meier survival analysis of TCGA BRCA dataset for the correlation between overall survival of breast cancer patients and TRIM46, BRCA1, or BLM expression. ",
    "ncbi_link": "BLM: 641
BRCA1: 672
TRIM46: 80128"
  },
  {
    "caption": "Kaplan-Meier analysis of the correlation between expression level of LOC113230 and overall survival of colon adenocarcinoma (COAD) patients from TCGA database. P<0.001. P-value for Kaplan-Meier curves was determined using log-rank test.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "qRT-PCR analysis of LOC113230 expression level in 65 paired CRC samples.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "Representative RNA-Scope immunostaining images of LOC113230 levels in CRC tissue and corresponding normal tissue from TMA chips. Scale bar represents 100 μM.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "Kaplan-Meier analysis for overall survival of CRC patients with high and low expression of LOC113230 from TMA chips. *P < 0.001. P-value for Kaplan-Meier curves was determined using log-rank test.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "Overexpression of LOC113230 in SW-1116 cells inhibited lung metastasis. Left: Exponentially growing SW-1116 - LOC113230-Luc and SW-1116-Vector-Luc cells were injected into the tail vein of 8-week-old nude mice and intensities of lung metastatic tumor cells at the 8th week were analyzed by in vivo photon flux imaging equipment. The red circles in images are to help to see the tumors. Right: Box plot (central band: median; box limits: first and third quartile; whiskers: minimum and maximum) of lung photon flux at the 8th weeks.",
    "ncbi_link": "Luc: 
LOC113230: 113230"
  },
  {
    "caption": "5 ng/ml TGF-β and DMSO were applied to stimulate SW-1116 -Vector or SW-1116 -LOC113230 cells for 24 and 48 hrs, respectively. Cell migration was detected by transwell assays. Scale bar represents 100 μM.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "I)Stable expression of LOC113230 300-800 inhibited cell migration, while LOC113230 antisense showed no apparent effect on cell migration. Scale bar represents 100 μM.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "(A)Top: Images taken by confocal microscopy showed the localization of LOC113230 detected by RNA scope assays in SW-1116. Scale bar represents 50 μM. Bottom: qRT-PCR assays showed LOC113230 expression level in the nuclear and cytoplasmic fractions extracted from SW-1116 cells.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "SW-1116 cells bearing stable expression or knockdown of LOC113230 were treated with MG132 (5 μM) for 12 hrs. Cell lysates were immunoprecipitated (IP) assays were performed with α-Flag antibody. The co-eluted proteins were detected by western blot assays with ubiquitin (Ub), ASS1 and α-Flag antibodies, respectively.",
    "ncbi_link": "LOC113230: 113230"
  },
  {
    "caption": "SW-1116 cells stably expressing ASS1WT, or ASS1 K234R and LOC113230 or not were treated with MG132 (5 μM) for 12 hrs. Cell lysates were immunoprecipitated (IP) assays were performed with α-Flag antibody. The co-eluted proteins were detected by western blot assays with ubiquitin (Ub) and α-Flag antibodies, respectively.",
    "ncbi_link": "ASS1: 445
LOC113230: 113230"
  },
  {
    "caption": "Depletion of ASS1 decreased cell migration in SW-1116 cells. Scale bar represents 100 μM.",
    "ncbi_link": "ASS1: 445"
  },
  {
    "caption": "Transwell assays showed the effect of ASS1WT and ASS1K234R on Caco-2-Vector or Caco-2-LOC113323 cell migration. Scale bar represents 100 μM..",
    "ncbi_link": "ASS1: 445
LOC113323: 113230"
  },
  {
    "caption": "(N) Kaplan-Meier analysis for overall survival of patients with high or low expression of ASS1. P < 0.001. P-value for Kaplan-Meier curves was determined using log-rank test.",
    "ncbi_link": "ASS1: 445"
  },
  {
    "caption": "SW-1116-LOC113230 cells transiently transfected with siRNAs to LRPPRC or TRAF2 or scrambled control (SiRNA-NC) were treated with MG132 (5 µM) for 12 hrs. Cell lysates were immunoprecipitated with α-Flag antibody. The precipitate proteins and input proteins were analyzed by immunoblotting. NC: Negative control.",
    "ncbi_link": "LRPPRC: 10128
LOC113230: 113230
TRAF2: 7186"
  },
  {
    "caption": "SIRT1 activity is required for resveratrol-induced autophagy but not for spermidine-mediated autophagy induction in mammalian cultured cells. (A-C) Human colon carcinoma HCT 116 cells were left untransfected (Co, control) or transfected with an irrelevant siRNA (UNR, unrelated) or siRNAs specific for ATG5, ATG7, or SIRT1 and then retransfected with a GFP-LC3-encoding plasmid, cultured in complete medium for 24 h, and left untreated or treated for 4 h with 100-µM resveratrol (Resv) or spermidine (Spd). The same experiment was performed in the presence of bafilomycin A1 (BafA1), which inhibits the fusion between lysosomes and autophagosomes, to evaluate the autophagic flux. (A) Representative images. (B) Quantitative data.",
    "ncbi_link": "ATG5: 9474
ATG7: 10533
LC3: 440738///81631///84557
SIRT1: 23411"
  },
  {
    "caption": "SIRT1 activity is required for resveratrol-induced autophagy but not for spermidine-mediated autophagy induction in mammalian cultured cells. (A-C) Human colon carcinoma HCT 116 cells were left untransfected (Co, control) or transfected with an irrelevant siRNA (UNR, unrelated) or siRNAs specific for ATG5, ATG7, or SIRT1 and then retransfected with a GFP-LC3-encoding plasmid, cultured in complete medium for 24 h, and left untreated or treated for 4 h with 100-µM resveratrol (Resv) or spermidine (Spd). The same experiment was performed in the presence of bafilomycin A1 (BafA1), which inhibits the fusion between lysosomes and autophagosomes, to evaluate the autophagic flux. (A) Representative images. (B) Quantitative data. (C) Representative immunoblots of HCT 116 cells transfected either with an unrelated siRNA or with a SIRT1-specific siRNA showing LC3 lipidation after treatment with 100-µM spermidine in the presence or absence of bafilomycin A1.",
    "ncbi_link": "LC3: 440738///81631///84557
SIRT1: 23411"
  },
  {
    "caption": "(D-F) HCT 116 cells were left transfected with a GFP-LC3 plasmid, cultured in complete medium for 24 h, and treated with either vehicle (Co), 100-µM resveratrol, or 100-µM spermidine in the presence or absence of the SIRT1 inhibitor EX527 for 4 h. (D) Representative images. (E) Quantitative data. (B and E) Bars depict the percentages of cells showing accumulation of GFP-LC3 in puncta (GFP-LC3vac; means ± SEM; n = 3; *, P < 0.05). (F) Representative immunoblots showing LC3 lipidation in HCT 116 cells treated with 100-µM spermidine in the presence or absence of EX527. GAPDH, glyceraldehyde 3-phosphate dehydrogenase.",
    "ncbi_link": "SIRT1: 23411"
  },
  {
    "caption": "The lifespan-extending and autophagy-inducing effects of spermidine in yeast are not mediated by Sir2. (A-E) EGFP-Atg8p was ectopically expressed in wild-type (WT) or Δsir2 S. cerevisiae undergoing chronological aging on small synthetic 2% glucose media with or without (Co, control) supplementation of 4-mM spermidine (Spd). (A) Representative images. EGFP-Atg8p localization (bottom) was visualized by fluorescence microscopy. Yeast cells undergoing autophagy (in which EGFP-Atg8p exhibits a prominent vacuolar localization) are indicated by arrows. Yeast morphology was monitored by differential interference contrast (DIC; top).",
    "ncbi_link": "Atg8p: 852200
Sir2: 851520
sir2: 851520"
  },
  {
    "caption": "(B) Representative immunoblots against EGFP. Free EGFP indicates the vacuolar degradation of EGFP-Atg8p fusion, thereby representing the autophagic flux. Notice that both WT and Δsir2 yeast cells show similar free EGFP levels after spermidine-mediated autophagy induction.",
    "ncbi_link": "Atg8p: 852200
sir2: 851520"
  },
  {
    "caption": "The life-extending and autophagy-inducing effects of spermidine in C. elegans are not mediated by Sir2. (A) Fluorescence microscopy of C. elegans transgenic embryos expressing a full-length plgg-1DsRed::LGG-1 fusion protein indicative of autophagic activity. Two representative pictures of wild-type (WT) and sir-2.1 embryos untreated (Co, control) or treated with 0.2-mM spermidine (Spd) supplementation of food are shown. (B) Quantification of autophagic activity through the measurement of DsRed::LGG-1 pixel intensity from images of WT animals shown in A. Data represent means ± SEM (n = 3) with ≥25 images processed for each trial.",
    "ncbi_link": "LGG-1: 174050
sir-2.1: 177924
Sir2: 177924"
  },
  {
    "caption": "C) Survival of WT C. elegans during aging with and without (control) supplementation of food (UV-killed E. coli) with 0.2-mM spermidine (n = 110; P < 0.005). (D) Survival of sir-2.1 C. elegans (ok434 phenotype) during aging with and without (control) supplementation of food (UV-killed E. coli) with 0.2-mM spermidine (n = 110; P < 0.01). P-values were calculated using the log-rank test as described in Materials and methods.",
    "ncbi_link": "sir-2.1: 177924"
  },
  {
    "caption": "Autophagy can be efficiently regulated by cytoplasmic (de)acetylation reactions. (A and B) HCT 116 cells were transfected with a GFP-LC3-encoding plasmid, cultured in complete medium for 24 h, and enucleated to obtain cytoplasts. The cytoplasts were treated with either vehicle (Co, control), 100-µM resveratrol (Resv), or 100-µM spermidine (Spd) for 4 h. 1-µM rapamycin (Rapa) was used as a positive control. (A) Representative images of cytoplasts indicative of autophagic activity. Arrows indicate GFP-LC3-transfected cytoplasts, whereas insets show nonenucleated transfected cells. (B) Quantitative data. Bars show the percentages of cells or cytoplasts showing the accumulation of GFP-LC3 in puncta (GFP-LC3vac).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(C-E) HCT 116 cells were cotransfected with a plasmid for the expression of RFP-LC3 together with an empty vector (pcDNA3) or plasmids encoding wild-type (WT) SIRT1 or a SIRT1 variant with a mutation in the nuclear localization signal fused to GFP (WT GFP-SIRT1 and mtNLS GFP-SIRT1, respectively) for 12 or 24 h, fixed, and analyzed by fluorescence microscopy. (C) Representative images indicative of 24-h autophagic activity.",
    "ncbi_link": "SIRT1: 23411"
  },
  {
    "caption": "Immunoblotting using an anti-4E-BP1 or anti-GAPDH (loading control) antibody of protein extracts from siCTR- or si4E-BP1-transfected CAFs (representative of n = 3).",
    "ncbi_link": "4E-BP1: 1978"
  },
  {
    "caption": "Immunoblotting of equal amounts of protein from siCTR- or si4E-BP1-transfected CAFs treated (+) or not with SOM230 for 48 h, using the anti-puromycin antibody (representative of n = 3).",
    "ncbi_link": "4E-BP1: 1978"
  },
  {
    "caption": "Panc-1 cell viability was assessed by MTT. Panc-1 cells were incubated with gemcitabine in the presence of CM from untreated or SOM230-treated CAFs transfected with the siCTR or si4E-BP-1. Results (mean ± SD) are presented as a percentage of the untreated CAFs (= 100%) (n = 3; **P = 0.003, §§P = 0.002).",
    "ncbi_link": "4E-BP-1: 1978"
  },
  {
    "caption": "A Expression of the somatostatin receptor subtype 1 (sst1) analysed by RT-qPCR in the human pancreatic endocrine cell line BON and in CAFs isolated from 11 different patients (mean ± SD).",
    "ncbi_link": "somatostatin receptor subtype 1: 6751
sst1: 6751"
  },
  {
    "caption": "H, I Immunoblotting of protein extracts from siCTR- or sisst1-transfected CAFs treated (+) or not with SOM230 for 48 h (sst1, puromycin and GAPDH as loading control, H) or for 30 min (P-Akt, P-S6, 4E-BP1 and GAPDH as loading control, I) (representative of n = 3).",
    "ncbi_link": "sst1: 6751"
  },
  {
    "caption": "J Panc-1 cell viability was assessed by MTT. Panc-1 cells were incubated with gemcitabine in the presence of CM from untreated or SOM230-treated CAFs transfected with siCTR or si-sst1. Results (mean ± SD) are presented as the percentage of the untreated cells (= 100%) (n = 3; **P = 0.003, §§P = 0.002).",
    "ncbi_link": "sst1: 6751"
  },
  {
    "caption": "E, F Immunoblotting using anti-P-Akt, anti-P-S6, anti-4EB-P1 or anti-GAPDH (loading control) antibody of protein extracts from CAF siCTR- or siSHP2- (E) or siPTPε- (F) transfected CAF treated or not with SOM230 for 30 min (representative of n = 3).",
    "ncbi_link": "SHP2: 5781
PTPε: 5791"
  },
  {
    "caption": "A-C MIA PaCa-2-GLuc cells were injected with or without CAFs into the pancreas of nude mice. Mice were treated with each indicated treatment (SOM230-LAR at day 7 and gemcitabine at days 7, 10, 14 and 17), and the plasmatic luciferase activity was measured (mean ± SD) at days 7, 14 and 21 (n = 5) (P = 0.003 for gemcitabine + SOM230LAR versus untreated) (A). Tumours were excised, photographed (scale bars are 1 cm) (B), weighted (P = 0.0008) (C) and paraffin-embedded for immunohistofluorescence analyses using an anti-cleaved caspase-3 antibody (E).",
    "ncbi_link": "GLuc: 
luciferase: "
  },
  {
    "caption": "B, C Anti-IL-6 ELISA assay (mean ± SD) using CM or protein extracts from SOM230-treated or not CAF (from left to right: §§§P = 0.0002, §§§P = 0.0002) (B), or CM from siCTR- or si4E-BP1-transfected CAFs treated or not with SOM230 (from left to right: ***P = 0.0003, $$P = 0.004) (C) (n = 3).",
    "ncbi_link": "4E-BP1: 1978"
  },
  {
    "caption": "D, E Plasma was collected from MIA PaCa-2GLuc and CAFs (*P = 0.034, **P = 0.007) (D), or human pancreatic tumour (*P = 0.028, **P = 0.004) (E), xenografts in nude mice and human IL-6 plasmatic concentrations (mean ± SD) were quantified by ELISA (n = 5 mice / group). * treated versus untreated mice.",
    "ncbi_link": "GLuc: "
  },
  {
    "caption": "RIP analyses of EGFP-MIWI2 in newborn testes from WT and Mili KO mice. RNA bound to EGFP-MIWI2 and input RNA were sequenced. All RNAs derived from each class was counted for this analysis.",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "DNA methylation status of a portion of the Rasgrf1 differentially methylated region (DMR) in 0−2-dpp Mili+/− and Mili−/− prospermatogonia. Regions corresponding to B, C, D, E, and F are demethylated in Mili−/− prospermatogonia. Vertical bars represent DNA methylation levels at CpG sites determined by whole genome bisulfite sequencing (see below). The top dark gray bar represents a portion of the Rasgrf1 gametic DMR (Tomizawa et al, 2011). The CpG cluster is shown. The deleted RMER4B sequence is indicated.",
    "ncbi_link": "Mili: 57746
Rasgrf1: 19417"
  },
  {
    "caption": "DNA methylation status of the Rasgrf1 DMR in Rasgrf1ΔRMER4B/ΔRMER4B and control spermatogonia are shown. The regions examined are shown in (A). Black (white) circles represent methylated (unmethylated) CpGs.",
    "ncbi_link": "Rasgrf1: 19417"
  },
  {
    "caption": "Rasgrf1 RMER4B functions in cis. Wild-type and mutant alleles of the Rasgrf1 DMR in Rasgrf1+/ΔRMER4B spermatogonia were analyzed separately.",
    "ncbi_link": "Rasgrf1: 19417"
  },
  {
    "caption": "Low expression level of piRNAs from chr7 cluster in chr7 piRNA clusterΔpromoter/Δpromoter testes. Unchanged expression of piRNAs from chr10 cluster (bottom) shows chr7 cluster is specifically affected. Only uniquely mapped piRNAs are shown.",
    "ncbi_link": "piRNA clusterΔpromoter/Δpromoter: "
  },
  {
    "caption": "DNA methylation status of the Rasgrf1 differentially methylated region (DMR) in spermatogonia from chr7 piRNA clusterΔpromoter/Δpromoter. See Figures 4A and B for information about the region examined.",
    "ncbi_link": "piRNA clusterΔpromoter/Δpromoter: 
Rasgrf1: 19417"
  },
  {
    "caption": "Depletion of piRNAs from chr7 piRNA cluster RMER4B sequence in chr7 piRNA clusterΔRMER4B/ΔRMER4B mice. Top panel shows overall view of chr7 piRNA cluster, and lower panel shows magnified view of RMER4B region in chr7 piRNA cluster. Only uniquely mapped piRNAs are shown.",
    "ncbi_link": "piRNA clusterΔRMER4B/ΔRMER4B: 
RMER4B: "
  },
  {
    "caption": "DNA methylation status of the Rasgrf1 differentially methylated region (DMR) in spermatogonia from chr7 piRNA clusterΔRMER4B/ΔRMER4B mice.",
    "ncbi_link": "Rasgrf1: 19417"
  },
  {
    "caption": "DNA methylation status of the Rasgrf1 differentially methylated region (DMR) in spermatocytes, spermatids, and sperms (D) from chr7 piRNA clusterΔRMER4B/ΔRMER4B mice.",
    "ncbi_link": "Rasgrf1: 19417"
  },
  {
    "caption": "DNA methylation pattern in the progeny of male Rasgrf1ΔRMER4B/ΔRMER4B mice. DNA methylation status of the Rasgrf1 DMR in E12.5 whole embryos is shown. E12.5 whole embryos were obtained by the crosses shown in the panel. Two independent bisulfite-treated DNA sample were examined for Homo13 embryo.",
    "ncbi_link": "Rasgrf1: 19417"
  },
  {
    "caption": "Protein-binding microarrays (PBM) were probed with PIF4-His, MBP-BES1 and the PIF4-His/MBP-BES1 complex. For PIF4-BES1 complex purification, both proteins were co-expressed in E. coli using the double expression pCOLADuet-1 vector. An anti-MBP antibody was used for BES1 and BES1-PIF4 signal detection, while PIF4 was detected with an anti-His antibody Electrophoretic mobility shift assays (EMSA) showing interaction of the PIF4, BES1, and PIF4-BES1 proteins with the conserved G-box, PBE-, and BRRE-elements in the PIL1 (At2g46970), PRE5 (At3g28857), and DWF4 (At3g50660) promoters. Increasing amounts of protein were used for the assay",
    "ncbi_link": "His: 
MBP: 
BES1: 838518
DWF4: 824229
PIF4: 818903
PIL1: 819311
PRE5: 2745895"
  },
  {
    "caption": "Protein-binding microarrays (PBM) were probed with PIF4-His, MBP-BES1 and the PIF4-His/MBP-BES1 complex. For PIF4-BES1 complex purification, both proteins were co-expressed in E. coli using the double expression pCOLADuet-1 vector. An anti-MBP antibody was used for BES1 and BES1-PIF4 signal detection, while PIF4 was detected with an anti-His antibody BES1 binds both BRRE- and G-box elements as a homodimer. A deletion of BES1 (delN) fused to MBP (MBP-delN) and the complete protein (MBP-BES1) were co-expressed in E.coli. Formation of intermediate mobility bands, indicative of DNA recognition by a dimeric form of the protein was tested in EMSA assays. A signal corresponding to the dimeric full-length MBP-BES1 and MBP-delN complex was detected with both DNA probes. Increasing amounts of the proteins were used in the assay",
    "ncbi_link": "His: 
MBP: 
BES1: 838518
PIF4: 818903"
  },
  {
    "caption": "Co-expression of the PIF4 and BES1 effector constructs leads to synergistic pPIL1 activation, and reverses BES1-dependent inhibition of the pDWF4 reporter. The pPIL1 and pDWF4 promoters including three G-boxes (green boxes) and two BRRE- elements (orange boxes) were fused to the firefly luciferase reporter gene (LUC) and co-transfected with 35S::PIF4, 35S::BES1 and 35S::bes1-D effector constructs into Nicotiana benthamiana leaves. Leaf discs were collected 48 hours after infiltration and luciferase activity was measured in a microplate luminometer.",
    "ncbi_link": "LUC: 
luciferase: 
BES1: 838518
bes1: 838518
DWF4: 824229
PIF4: 818903
PIL1: 819311"
  },
  {
    "caption": "Time course analysis of BES1 protein accumulation levels. pBES1::BES1-GFP seedlings were grown under short days for 6 days and samples were harvested each 2 hours for a 24 h interval. Total protein extracts were used for western blot analysis with an anti-GFP antibody to detect the BES1-GFP protein. Hybridization with anti-RPT5 antibody is included as a loading control. Dark and light periods are represented as black and white bars, respectively. The experiment was repeated twice with similar results",
    "ncbi_link": "GFP: 
BES1: 838518"
  },
  {
    "caption": "Diurnal oscillation of BES1 and BZR1 transcripts. Col-0 seedlings were grown for 6 days under short days and samples were harvested every 3 hours. BES1 and BZR1 expression levels were determined by qRT-PCR analyses and normalized to PP2A. Relative levels are the mean of three technical replicates and error bars represent standard deviation. The experiment was performed three times with similar results. Dark periods are indicated by shading",
    "ncbi_link": "PP2A: 
BES1: 838518
BZR1: 843845"
  },
  {
    "caption": "Western blot analyses of 35S::BES-GFP seedlings grown for six days under short days. Samples were collected every two hours, starting two hours before lights on (ZT-2) to ZT6. Western blots were hybridized with an anti-GFP antibody to detect the BES1-GFP protein, and anti-RPT5 as a loading control",
    "ncbi_link": "GFP: 
BES: 838518"
  },
  {
    "caption": "BES1 but not BZR1 is stabilized in the light. 35S::BES1-GFP and 35S::BZR1-GFP seedlings were grown for 6 days in continuous white light (WL), red light (RL), and continuous dark (DARK), and the BES1 and BZR1 proteins analyzed by western blot using an anti-GFP antibody. Hybridization with an anti-RPT5 antibody was used as a loading control",
    "ncbi_link": "GFP: 
BES1: 838518
BZR1: 843845"
  },
  {
    "caption": "BES1 accumulation is independent of brassinosteroid levels. Six day-old 35S::BES-GFP seedlings were treated overnight with 100 nM epi-brassinolide (BL) or 0.5 µM brassinazole (BRZ). Material was collected at the indicated time points and analyzed by western blot hybridization with anti-GFP and -RPT5 antibodies",
    "ncbi_link": "GFP: 
BES: 838518"
  },
  {
    "caption": "In vivo analysis of PIF4-BES1 complex formation. Six day-old pPIF4::PIF4-HA seedlings grown under short day conditions were collected at ZT0, ZT1 and ZT8. PIF4-HA was immunoprecipitated with an anti-HA antibody and the pulled-down BES1 protein immunodetected with an anti-BES antibody. * Indicates a non-specific band by the primary antibody used to immunoprecipitation.",
    "ncbi_link": "HA: 
PIF4: 818903"
  },
  {
    "caption": "Col-0 (black), PIF4-OX (red) and pifq (blue) seedlings were grown for 6 days under short days and samples harvested at the indicated time points. Total RNA was used for qRT-PCR quantification of PIF+BES-UP and the BR biosynthetic BES-DOWN transcripts, using PP2A as endogenous control. Error bars represent SD of three technical replicates. Dark periods are shown in grey. Relative expression of the XTR7, PRE5, IAA19 and BR6ox2 genes in PIF4-OX lines are referred to the right y axis of the graph. The experiment was repeated three times with similar results.",
    "ncbi_link": "PP2A: 
BR6ox2: 822709
IAA19: 820793
PIF4: 818903
pifq: 819311///816538///818903///837479
PRE5: 2745895
XTR7: 829936"
  },
  {
    "caption": "Col-0 and pifq seedlings were grown under short days at 22ºC and 28ºC, and samples were collected at the indicated time points. Expression of BR biosynthetic genes was analyzed by qRT-PCR, using the constitutive PP2A gene as internal control. Error bars represent SD of three technical replicates. The experiment was repeated twice with similar results",
    "ncbi_link": "PP2A: 
pifq: 819311///816538///818903///837479"
  },
  {
    "caption": "Activation of the XTR7 PIF+BES-UP target was studied as a positive control of the experiment. Error bars represent SD of three technical replicates. Dark periods are shown in grey. The experiment was performed three times with similar results",
    "ncbi_link": "XTR7: 829936"
  },
  {
    "caption": "Increased levels of de-phosphorylated BES1 at elevated temperatures depend on PIFs activation of BR synthesis. Col-0 and pifq seedlings were grown for 6 days under short days and 22ºC or 28ºC, on half strength MS media (mock) or media supplemented with 0.5 µM BRZ. BES1 was analyzed by western blot hybridization with an anti-BES1 antibody. RPT5 was used as a loading control.",
    "ncbi_link": "pifq: 819311///816538///818903///837479"
  },
  {
    "caption": "(A) Representative double-plotted actograms showing wheel-running activity of wild type (WT) and CRY-deficient (CRY Knockout; CKO) mice during constant light (yellow shading) and thereafter in constant darkness. Note the 48 hour x-axis for WT versus 32 hour for CKO.",
    "ncbi_link": "CRY: 12953///12952"
  },
  {
    "caption": "(C) Per2 mRNA levels in WT (left) and CKO (right) cells were determined by qPCR over one circadian cycle (bottom), while PER2::LUC bioluminescence (top, min-max normalised) was recorded from parallel cultures. Per2 mRNA reported relative to Rns18s (bottom), n=3, ±SEM; PER2::LUC (top) presented as mean (solid) ±SEM (dashed), n=3. The WT mRNA trace was preferentially fit by a circadian damped sine wave compared with straight line (p=0.0412, extra sum-of-square F-test) whereas CKO data was not (ns).",
    "ncbi_link": "Rns18s: 
Per2: 18627"
  },
  {
    "caption": "(D) Detrended Per2 and Nr1d1 promoter activity in WT, CKO and quadruple Cry1/2-Per1/2 knockout (CPKO) mouse embryonic fibroblasts (MEFs) recorded at 37°C, n=3, mean (solid) ±SEM (dashed). Nr1d1 data were preferentially fit with a circadian damped sine wave over straight line (p<0.0001, extra sum-of-squares F-test) (right hand graphs, solid lines; error bars, SEM).",
    "ncbi_link": "Cry1: 12952
Nr1d1: 217166
Per1: 18626
Per2: 18627"
  },
  {
    "caption": "Assessment of mtDNA damage by quantitative PCR. HEK293 cells infected with control (empty vector) or shATG5 for 5 days. Cells were then incubated with DMSO or 4 mM 3-NPA for 2 h and either immediately harvested or washed with fresh medium and incubated for another 1 h. Cells with or without washout were used for the extraction of total DNA. All DNA samples were used for amplification of 8.9 kb mtDNA fragment using quantitative PCR and were normalized to amplification of a 221 bp mtDNA fragment. PCR products were quantitated by PicoGreen staining using Micro Plate Reader. Data are presented as mean ± SD (n = 3 independent experiments), statistical significance was assessed by two-tailed student's t-test, N.S., not significant, *p < 0.05, **p < 0.01. The data in (A) were further calculated for the frequency of mtDNA damage. The equation was seen in "Materials and Methods". Data are presented as mean ± SD (n = 3 independent experiments), statistical significance was assessed by a two-tailed student's t-test, N.S., not significant, **p < 0.01.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "Representative images show 8-oxo-dG staining. Control or shATG5 HeLa cells were treated with DMSO, 200 µM H2O2, or 4 mM 3-NPA for 2 h, and then either fixed immediately or washed with fresh medium and incubated for another 1 h. Cells were immunostained with DAPI and anti-8-oxo-dG antibody and analyzed by confocal microscopy. Scale bar, 10 µm. Quantification of the relative 8-oxo-dG fluorescence intensity in (C). Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by a two-tailed student's t-test, N.S., not significant, *p < 0.05, **p < 0.01.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "Control or shATG5 HEK293 cells stably expressing mito-Keima. Control cells were treated with DMSO, 200 µM H2O2, or 4 mM 3-NPA for 2 h, and shATG5 cells were treated with 200 µM H2O2 as a negative control. Cells were then imaged with 458 nm (measuring mitochondria with a neutral pH) and 561 nm (measuring mitochondria with an acidic pH) laser excitation for mito-Keima by confocal microscopy. Right panels show the pixel intensity of red (mitochondria within lysosomes) and green (mitochondria in the cytoplasm) from a line. Scale bar, 10 µm. Quantification of the relative ratio of red to green fluorescence intensity (561 nm/458 nm) of the cells described in (E). Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by a two-way ANOVA, N.S., not significant, **p < 0.01.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "Screening of mitophagy regulators for removing damaged mtDNA. HeLa cells were infected by lentiviral particles containing the indicated knockdown vectors. Five days later, cells were treated with 200 µM H2O2 for 2 h. Cells were then imaged with 458 nm (measuring mitochondria with a neutral pH) and 561 nm (measuring mitochondria with an acidic pH) laser excitation for mito-Keima. ShATG5 was used as a negative control. Right panels for each image show the FACS-based mito-Keima dot plots. The y-axis represents the fluorescence emission of mito-Keima at pH 4.0 (lysosome), while the x-axis indicates mito-Keima at pH 7.0 (mitochondria). The percentages of cells within the different regions are indicated. Scale bar, 10 µm.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "Control or ATAD3B KO HeLa cells stably expressing mito-Keima were treated with 4 mM 3-NPA for 2 h and imaged with 458 nm (measuring mitochondria with a neutral pH) and 561 nm (measuring mitochondria with an acidic pH) laser excitation for mito-Keima by confocal microscopy. Scale bar, 10 µm. Quantification of the relative ratio of red to green fluorescence intensity (561 nm/458 nm) of the cells described in (B). Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by two-tailed student's t-test, N.S., not significant, **p < 0.01.",
    "ncbi_link": "ATAD3B: 83858"
  },
  {
    "caption": "Control or KO ATAD3B HeLa cells were treated with 4 mM 3-NPA for 2 h. Cells were washed with fresh medium and incubated for another 1 h. Cells were then fixed and immunostained with DAPI and anti-8-oxo-dG antibodies and were analyzed by confocal microscopy. Scale bar, 10 µm. Quantification of the relative 8-oxo-dG fluorescence intensity in cells described in (D). Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by two-tailed student's t-test , N.S., not significant, **p < 0.01.",
    "ncbi_link": "ATAD3B: 83858"
  },
  {
    "caption": "PINK1 KO HeLa cells stably expressing mito-Keima were infected with control or shATAD3B. Five days later, cells were treated with DMSO, 200 µM H2O2, or 4 mM 3-NPA for 2 h. Cells were then analyzed and imaged with 458 nm (measuring mitochondria with a neutral pH) and 561 nm (measuring mitochondria with an acidic pH) laser excitation for mito-Keima by confocal microscopy. Scale bar, 10 µm. Quantification of the relative ratio of red to green fluorescence intensity (561nm/458nm) of the cells described in (A). Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by two-tailed student's t-test, N.S., not significant, **p < 0.01.",
    "ncbi_link": "ATAD3B: 83858
PINK1: 65018"
  },
  {
    "caption": "PINK1 KO HeLa cells stably expressing ATAD3A-Flag (3A-Flag) or ATAD3B-Flag (3B-Flag) were mixed with control PINK1 KO cells respectively, and incubated for 24 h. Cells were treated with 4 mM 3-NPA (D) or 200 µM H2O2 (F) for 2 h, and then washed with fresh medium and incubated for another 1 h. Cells were fixed and immunostained with anti-8-oxo-dG and anti-Flag antibodies and analyzed by confocal microscopy. 8-oxo-dG fluorescence intensity of cells treated with 3-NPA (E) or H2O2 (G) was quantified by ImageJ software. Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by individual two-tailed student's t-test, N.S., not significant, *p < 0.05, **p < 0.01. Scale bar, 10 µm.",
    "ncbi_link": "Flag: 
ATAD3A: 55210
ATAD3B: 83858
PINK1: 65018"
  },
  {
    "caption": "Control (GFP+) and shATAD3B (GFP-) PINK1 KO HeLa cells were mixed and incubated for 24 h. Cells were then treated with 4 mM 3-NPA (H) or 200 µM H2O2 (J) for 2 h, and washed with fresh medium, and incubated for another 1 h. Cells were fixed and immunostained with anti-8-oxo-dG and DAPI, then analyzed by confocal microscopy. Control or shATAD3B cells are circled by white dashed lines. 8-oxo-dG fluorescence intensity of cells treated with 3-NPA (I) or H2O2 (K) was quantified using ImageJ software. Data are presented as mean ± SD (n = 3 independent experiments, 20 cells per experiment), statistical significance was assessed by two-tailed student's t-test, **p < 0.01. Scale bar, 10 µm.",
    "ncbi_link": "ATAD3B: 83858
PINK1: 65018"
  },
  {
    "caption": "ATAD3 DKO HeLa cells expressing GFP-LC3B were transiently transfected with control, ATAD3A-Flag or ATAD3B-Flag. 48 h after transfection, cell lysates were immunoprecipitated (IP) with anti-Flag M2 affinity gel, and analyzed by Western blotting using anti-Flag or anti-GFP antibodies.",
    "ncbi_link": "Flag: 
GFP: 
LC3B: 
ATAD3A: 55210
ATAD3B: 83858
ATAD3: 83858///55210"
  },
  {
    "caption": "HeLa expressing GFP-LC3 monoclonal cell line was infected with lentivirus particles containing control or shATAD3B. Five days later, cells were treated with DMSO, or 200 µM H2O2 for 2 h. Cells were fixed and immunostained with anti-Tom20 and imaged by confocal microscopy. The white arrows indicate the LC3 puncta colocalizing or contacting with Tom20 (mitochondria). Scale bar, 10 µm.",
    "ncbi_link": "ATAD3B: 83858"
  },
  {
    "caption": "293T cells transiently transfected with control or ATAD3B-Flag were treated with or without 200 µM H2O2 for 2 h. Cell lysates were then immunoprecipitated with Dynabeads Protein G pre-coupled with anti-Flag antibody, followed by Western blotting with anti-Flag or anti-LC3B antibodies. Relative protein levels of LC3B and ATAD3B-Flag were further evaluated by densitometry",
    "ncbi_link": "Flag: 
ATAD3B: 83858"
  },
  {
    "caption": "Mic10 KO COS7 cells stably expressing ATAD3A-Flag or ATAD3B-Flag were treated with DMSO or 200 µM H2O2 for 2 h, and then fixed and immunostained with anti-Tom20 and anti-Flag antibodies, and analyzed by confocal microscopy. Scale bar, 10 µm.",
    "ncbi_link": "Mic10: "
  },
  {
    "caption": "Control, ATAD3A KO, ATAD3B KO, or ATAD3 DKO HeLa cells were harvested for mitochondrial isolation. Purified mitochondria were treated with DMSO or EDC (20 mM) for 30 min, and then were analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "ATAD3A: 55210
ATAD3B: 83858
ATAD3: 83858///55210"
  },
  {
    "caption": "ATAD3A KO HeLa cells were harvested for mitochondrial isolation. Purified mitochondria were treated with the indicated gradient concentration of proteinase K for 20 min on ice, and then were analyzed by Western blotting with anti-ATAD3, anti-Tom20 (OMM), anti-Tim23 (IMS), and anti-HSP60 (matrix) (K). Relative protein levels of proteins in (K) were further evaluated by densitometry analysis using ImageJ software. Relative trends of proteolysis of indicated mitochondrial proteins from ATAD3A KO HeLa cells were shown (L). Data are presented as mean ± SD (n = 3 independent experiments).",
    "ncbi_link": "ATAD3A: 55210"
  },
  {
    "caption": "ρ0206_B cells were infected with control, ATAD3B-Flag or ATAD3B (mLIR)-Flag. After two weeks, total DNA from cells was isolated and used to calculate the mutation rate of 3243A>G by quantitative real-time PCR using the TaqMan Probe. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by a one-way ANOVA, N.S., not significant, *p < 0.05.",
    "ncbi_link": "Flag: 
ATAD3B: 83858"
  },
  {
    "caption": "ρ0206_B cells were infected with control, ATAD3A-Flag, ATAD3B-Flag, or ATAD3B (mLIR)-Flag. After two weeks, the cellular ATP levels were measured. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by a one-way ANOVA, N.S., not significant, *p < 0.05.",
    "ncbi_link": "Flag: 
ATAD3A: 55210
ATAD3B: 83858"
  },
  {
    "caption": "MELAS patient fibroblasts were infected with control, ATAD3A-Flag, ATAD3B-Flag or ATAD3B(mLIR)-Flag. After two weeks, total DNA was isolated from fibroblasts and used to calculate the mutation rate of 3243A>G by quantitative real-time PCR using the TaqMan Probe. Data are presented as mean ± SD (n =3 independent experiments), statistical significance was assessed by a one-way ANOVA, N.S., not significant, **p < 0.01.",
    "ncbi_link": "Flag: 
ATAD3A: 55210
ATAD3B: 83858"
  },
  {
    "caption": "B Immunoblotting of protein extracts from SKMEL5 cells transfected with siCTRL or the combination siDDR1#2/siDDR2#2 prior being cultivated on FRC- or MAF-derived ECMs (left and right panels, respectively) and treated with vehicle, 5 µM BRAFi or 2 µM BRAFi plus 0.01 µM MEKi, using antibodies against the indicated proteins. HSP60, loading control.",
    "ncbi_link": "DDR1: 780
DDR2: 4921"
  },
  {
    "caption": "A Immunoblot analysis of protein extracts from siCTRL- or siDDR1/2-transfected SKMEL5 cells plated on FRC- or MAF-derived ECMs in the presence or not of 5 µM BRAFi, 2 µM BRAFi plus 0.01 µM MEKi for 96 h using antibodies against DDR1, DDR2, P-ERK1/2, ERK2, RelB, p100/p52 and HSP60 as loading control were used.",
    "ncbi_link": "DDR1: 780"
  },
  {
    "caption": "B WT and SirT7-/- mice at 10 days (top) and 2 months (bottom) of age.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "C Weight distribution of WT and SirT7-/- mice (n=3-10 female mice per time point and genotype; P value = 0.003 by unpaired t-Test).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "Kaplan Meier survival curves (n=170 WT and n=58 SirT7-/- mice; Log-rank Test P value <0.0001).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "A Representative 3D reconstructed CT scans showing increased kyphosis in 16 month old SirT7-/- mice compared with WT.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "B Representative gonadal fat pads from WT and SirT7-/- 16 month old mice.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "E, F Dot plots of Lin-Sca1+cKit+ (LSK) cells (middle and right) from WT and SirT7-/- bone marrow cells. Cells were gated for negative staining of lineage markers B220, CD3, CD11b, CD19, Gr-1, and Ter-119 (Left), and analyzed for Sca1 and cKit expression (middle and right). (F) Quantitation of (E) (mean ± SEM; 4 mice per genotype).",
    "ncbi_link": "Lin: 
cKit: 16590
Sca1: 110454
SirT7: 209011"
  },
  {
    "caption": "G Bone marrow, thymus, and spleen cell number in young WT and SirT7-/- mice (mean ± SEM; 3-5 mice per genotype).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "H mRNA expression of p16 gene normalized to GAPDH measured by RT-PCR from young and old WT and SirT7-/- fibroblasts (mean ± SEM; 3 samples per genotype).",
    "ncbi_link": "GAPDH: 
p16: 12578
SirT7: 209011"
  },
  {
    "caption": "I, J Senescence-associated β-galactosidasestaining (I, blue) in HT1080 cells transfected with Scramble Control or SirT7 Knockdown and grown for 7 days in selection media. (J) Quantitation of the number of senescent cells shown in (I) (mean ± SEM; 3 independent cell lines per genotype).*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by ANOVA Single Factor.",
    "ncbi_link": "SirT7: 51547"
  },
  {
    "caption": "A, B Dot plots of FACS cell cycle analyses of WT and SirT7-/- MEFs in passage 3 (P3) and 6 (P6) using EdU incorporation and 7AAD (A). Percentages of cells in Sub G1 (apoptotic cells, left square) and cells with DNA content above 4N (polyploid, right square). (B) Quantitation of experiment shown in (A) (mean ± SEM; 3 samples per genotype).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "C Survival curve for WT and SirT7-/- thymocytes after X-Ray irradiation (IR) at the indicated doses. Cell death was quantified by FACS using AnexinV and 7AAD staining 18 hours post insult (mean ± SEM; 3 samples per genotype from one of two independent experiments).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "D Clonogenic assays in HT1080 cells transfected with Scramble Control or SirT7 Knockdown and irradiated at the indicated X-Ray doses, then plated at low density. After 9 days, colonies were stained with crystal violet and counted (mean ± SEM; 3 independent cell lines per genotype).",
    "ncbi_link": "SirT7: 51547"
  },
  {
    "caption": "F Quantitation of experiment shown in (E) (mean ± SEM; 9 WT and 3 SirT7-/- samples).*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA Single Factor.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "A Quantitation of neutral comet assays, using passage 3 WT and SirT7-/- primary MEFs, showing (left) the amount (%) of DNA in the tail and (right) the tail moment (see Fig S3A for representative images).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "B Western blot showing ATM and KAP1 phosphorylation and total protein levels in WT and SirT7-/- primary fibroblasts after IR (8Gy). ATM inhibitor (ATMi) KU-55933 was added 30 min prior to irradiation where indicated. One representative blot from 4 independent experiments is shown.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "C-F IF analysis of WT and SirT7-/- primary fibroblasts showing γH2AX dynamics after DNA damage induction. Cells were untreated (NoIR) or treated with 1Gy of X-rays (IR) and fixed at the indicated times post insult. Cells were pulsed with EdU (green) 30 min prior to fixation, then stained for γH2AX (red) and counterstained with DAPI (blue) (n>30 cells per group/mice; 3 mice per genotype). (C) Representative images of untreated S-phase (NoIR, EdU positive) WT and SirT7-/- nuclei (scale bar 5µm). (D) Quantitation of the number of γH2AX foci per nucleus at the indicated time points post IR (1Gy), and indicated cell cycle phases. (E) Quantitation of experiment described in (C) showing mean number of γH2AX foci per nucleus in euchromatic and heterochromatic regions at the indicated time points before and after IR in G2 (mean ± SEM from 3 independent experiments). Total γH2AX foci and γH2AX foci overlapping with or at the periphery of heterochromatic regions were enumerated. Nuclei and pericentric heterochromatin (chromocenters) were segmented by DAPI staining. Euchromatic numbers were estimated by subtracting the heterochromatic number of foci from the total foci number.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "(F) Representative images of WT and SirT7-/- primary fibroblasts in G2 phase showing γH2AX (red) and DAPI (blue) at the indicated period of time after IR. (Right) 3D rendering of the IF segmentation depicting nuclei (pale blue), chromocenters (darker blue), and γH2AX (yellow denotes foci associated with pericentric heterochromatin, otherwise foci are red). Scale bar 2 µm.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "G FACS quantitation of WT and SirT7-/- MEF cells in S-phase after insult with 10 mM hydroxyurea (HU) for 24 hours. Cells were fixed and stained with 7AAD and cell cycle was monitored by FACS (mean ± SEM; 5 samples per genotype).",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "H, I DNA fiber labeling analysis was used to assess DNA replication fork progression in passage 3 and passage 6 primary WT and SirT7-/- MEFs. (H) Representative images from cells labeled for 20 min with IdU (green) followed by 20 min of CldU (red). (I) Quantitation of fork velocity (fiber length/labeling time; mean ± SEM; 3 samples per genotype per condition).*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA Single Factor.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "A-E IF analysis of WT and SirT7-/- primary fibroblasts after IR (1Gy) and 1 hour chase. Cells were pulsed with EdU 30 min prior to fixation, stained with antibodies against γH2AX and 53BP1 and then counterstained with DAPI (scale bar 5µm). (A) Representative images from each cell cycle stage showing merge (top-left) including EdU (green), 53BP1 (top-right, magenta), γH2AX (bottom-left, red), and 3D rendering of reconstructed Z-stacks with 53BP1 foci modeled as spheres (bottom-right; pale-blue: nucleus; magenta spheres: 53BP1 foci). (B) Quantitation of the number of 53BP1 foci per nucleus, and (C) mean volume of 53BP1 foci (n>30 cells per group/mice; 3 mice per genotype). (D-E) Same as in (B-C), upon overexpression of SIRT7 WT or catalytically inactive point mutant SIRT7-H188Y in WT and SirT7-/- primary fibroblasts.",
    "ncbi_link": "SIRT7: 209011
SirT7: 209011"
  },
  {
    "caption": "F Detection of endogenous chromatin-bound and nucleoplasmic 53BP1 protein from WT and SirT7-/- MEFs before and after IR (8Gy) by western blot. Histone H3 was used as loading control, and tubulin as control for fractionation.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "G Same as (F), using 293T-REX cells treated with doxycycline or vehicle to induce SIRT7-HA expression.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "H ChIP-on break assay. (Top) Schematic of I-SceI substrate construct introduced into HT1080 cells, which contains a single I-SceI site located within a puromycin resistance cassette. Shown along the top are the coordinates for amplicons probed by Q-PCR. (Bottom) 53BP1 enrichment at the indicated loci in Scramble control or SirT7 knockdown cells. Q-PCR measurements were normalized to input DNA and non-I-SceI treated samples (No Cut) (mean ± SEM; one of two independent experiments shown). (Bottom Right) western blot demonstrating efficient knockdown of SirT7, with Histone H3 as a loading control.",
    "ncbi_link": "I-SceI: 854590
SirT7: 51547
53BP1: 7158"
  },
  {
    "caption": "I, J NHEJ repair assay using GFP expression-based reporter system in SirT7-depleted HT1080 cells (SirT7 Knockdown) versus control (Scramble Control). (I) Representative FACS dot plots. (J) Quantitation of (I); mean ± SEM of 3 independent clones per condition. Values are normalized to control (Scramble Control + I-SceI) mean.",
    "ncbi_link": "SirT7: 51547"
  },
  {
    "caption": "K, L Class-switch recombination in splenic B cells from WT and SirT7-/- mice stimulated with lipopolysaccharides (LPS) and interleukin 4 (IL4). (K) The switching from IgM to IgG1 (left) and to IgG3 (right) was measured by FACS. (L) Quantitation of (K) showing mean ± SEM of 3-4 samples per genotype. One representative experiment from two is shown.*P < 0.05; **P < 0.01; ***P < 0.001 by ANOVA Single Factor.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "A, B H3K18Ac IF in WT and SirT7-/- fibroblasts. Cells were pulsed with EdU (green), stained with antibody against H3K18Ac (magenta) and then counterstained with DAPI (blue). (A) Representative IF images of late S-phase nuclei (EdU positive; scale bar 5µm). (B) Quantitation of (A) throughout the cell cycle.",
    "ncbi_link": "SirT7: 209011"
  },
  {
    "caption": "E ChIP assays of SIRT7 enrichment at the indicated loci as described in Figure 5H (mean ± SEM; one of two independent experiments is shown).",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "F Recruitment kinetics of GFP-tagged SirT7 after laser-induced microirradiation. (Top) Representative cell at the indicated times after induction of DNA damage (white circle; scale bar 2µm). Images were adjusted to account for photobleaching by normalizing to nucleoplasmic background signal. (Middle) Quantitation of recruitment kinetics at the site of induced damage in the presence of 5M KU-55933 ATM inhibitor (ATMi), 10M Olaparib PARP inhibitor (PARPi), or DMSO. KU-55933 and Olaparib were added 30 min and 1 hour respectively prior to DNA damage (mean ± SEM; sample size: SIRT7-GFP, n=34; SIRT7-GFP + ATMi, n=36; SIRT7-GFP + PARPi=18). (Bottom) Same as (middle) except quantitation of SIRT7-GFP relative intensity within the nucleolus. Data was acquired at five second intervals over a span of five min.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "G ChIP assays of H3K18Ac enrichment at the indicated loci as described in Figure 5H. H3K18Ac enrichment adjacent to the induced DSB in control and SIRT7 depleted cells (bottom left), or in cells overexpressing SIRT7 in the presence or absence of PARP inhibitors (PARPi) (bottom right) (mean ± SEM; one of two independent experiments is shown).*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by ANOVA Single Factor.",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "A-H NHEJ activity in HT1080 or NIH3T3 cells stably overexpressing H3-WT, H3-K18Q or H3-K18R (naive, acetylated or deacetylated H3K18 residues, respectively).A Random integration assay in HT1080 cells using a linearized pSMCV vector containing a puromycin resistance cassette (mean number of puromycin resistant colonies normalized by plating efficiency ± SEM; One representative transfection from 3 is shown).",
    "ncbi_link": "H3: 3020///333932///8350"
  },
  {
    "caption": "E Western blot analysis of 53BP1 in chromatin and non-chromatin fractions from NIH3T3 cells expressing H3-WT, H3-K18Q or H3-K18R vectors and exposed to IR (10Gy). One representative blot is shown from 3 independent experiments. Shown is 53BP1, GAPDH for fractionation control, and H3 for loading control.",
    "ncbi_link": "H3: 15078///319150///360198"
  },
  {
    "caption": "I 53BP1 enrichment at the indicated loci as described in Figure 5H in Scramble control or SirT7 knockdown cells expressing the indicated H3 constructs (mean ± SEM; one of two independent experiments).",
    "ncbi_link": "H3: 3020///333932///8350
SirT7: 51547
53BP1: 7158"
  },
  {
    "caption": "J Western blot analysis of chromatin fractions from primary WT and SirT7-/- MEFs expressing the indicated H3 constructs and exposed to IR (10Gy). Shown are levels of 53BP1, SIRT7, H3-Myc, GAPDH for fractionation control, and H3 for loading control.",
    "ncbi_link": "H3: 15078///319150///360198
SirT7: 209011"
  },
  {
    "caption": "B MAPKKK5-C interacts with PBL27 in yeast two-hybrid experiments. The growth of yeast colonies on plates (-ULWH) lacking uracil (U), leucine (L), tryptophan (W), and histidine (H) with 2 mM 3-aminotriazole (3-AT) indicates a positive interaction.",
    "ncbi_link": "MAPKKK5: "
  },
  {
    "caption": "D Complementation of chitin-induced MAPK activation in mapkkk5 mutants by expression of MAPKKK5-FLAG. MAPK activation was analyzed by immunoblots with α-pMAPK.",
    "ncbi_link": "mapkkk5: 836819
MAPKKK5: 836819"
  },
  {
    "caption": "A Chitin-induced callose deposition in the mapkkk5 mutants. Seedlings were analyzed at 18 hours after treatment with 10 μM chitin. Representative pictures from the biological replicates are presented. Data are means ±SD from three independent biological replicates, where each biological replicate consists of two technical replicates. The asterisks indicate statistically significant differences from the WT controls by Student's t-test (P < 0.05).",
    "ncbi_link": "mapkkk5: 836819"
  },
  {
    "caption": "C mapkkk5 mutations reduce resistance to Alternaria brassiciicola. Lesions sizes were measured 6 days after inoculation. Values are mean ±S.E., n ≥92. Asterisks indicate significant difference from wild-type controls by Student's t-test (P < 0.01).",
    "ncbi_link": "mapkkk5: 836819"
  },
  {
    "caption": "D Analysis of chitin-induced transcriptional reprogramming in mapkkk5-1. Total RNA was extracted from seedlings treated with mock or 40 μM chitin for 3 hours and analyzed by RNA-seq. Genes that are significantly induced or suppressed by chitin in the wild type were selected (q-value < 0.05; 12,992 genes). The log2 fold changes of the selected genes compared to mock in the wild type and mapkkk5-1 were plotted. Yellow and blue dots indicate genes that show reduced induction or suppression (506 genes) or enhanced induction or suppression (151 genes) in mapkkk5-1 compared to the wildtype, respectively. The slope of the linear regression line (red) indicates that the overall transcriptional response is weakened in mapkkk5-1 compared to the wild type. As a comparison, the line y=x (black) is shown. For more details, see the Methods.E A heatmap showing MAPKKK5-dependent genes. Genes showing reduced induction or suppression in mapkkk5-1 compared to the wild type were selected as described in the Methods (339 genes). The log2 fold changes of the selected genes compared to mock were subjected to hierarchical clustering analysis. Yellow indicates positive values, blue indicates negative values and black indicates zero: see the color scale.",
    "ncbi_link": "mapkkk5: 836819
MAPKKK5: 836819"
  },
  {
    "caption": "F Expression patterns of representative MAPKKK5-dependent genes. qRT-PCR analysis of defense-related genes in 8-day-old seedlings exposed to 40μM (GlcNAc)7 for 3h. Data are shown as the average of three independent biological replicates ± SD. The asterisks indicate statistically significant differences from the WT controls by Student's t-test (P < 0.05).",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "C Detection of MAPKKK5-GFP and PBL27-HA transiently expressed in Nb leaves. Total proteins were purified from Nb leaves at 38 hpi.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "E Co-immunoprecipitation assays show that MAPKKK5K375M-GFP forms the complex with PBL27-HA in Nb leaves. The microsomal fractions purified from Nb leaves co-expressing MAPKKK5K375M-GFP and PBL27-HA at 48 hpi were used for co-immunoprecipitation with α-GFP.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "A Detection of MAPKKK5-GFP and MAPKKK5K375M-GFP transiently expressed in Arabidopsis protoplasts.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "B Expression of MAPKKK5-GFP reduces the level of PBL27. CBB, Coomassie brilliant blue.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "D The co-immunoprecipitation assay shows that PBL27 forms the complex with MAPKKK5 in Arabidopsis protoplasts. Total proteins purified from protoplasts co-expressing PBL27 and MAPKKK5 were subjected to immunoprecipitation with α-HA.",
    "ncbi_link": "PBL27: 831979
MAPKKK5: 836819"
  },
  {
    "caption": "A PBL27 phosphorylates MAPKKK5-C in vitro. The in vitro phosphorylation reaction was carried out using [32P]γ-ATP, and the phosphorylated proteins were detected by autoradiography. CBB, Coomassie brilliant blue.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "B BIK1 does not phosphorylate MAPKKK5-C in vitro. RBOHD was used as a positive control. Asterisk indicates artificial bands.",
    "ncbi_link": "MAPKKK5: 836819
RBOHD: 834842"
  },
  {
    "caption": "E PBL27 does not phosphorylate MAPKKK5-C6xAin vitro. The in vitro phosphorylation reaction was carried out using [32P]γ-ATP, and the phosphorylated proteins were detected by autoradiography.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "F PBL27 interacts with MAPKKK5-C6xA in yeast two-hybrid experiments. The growth of yeast colonies on plates (-ULWH) lacking uracil (U), leucine (L), tryptophan (W), and histidine (H) with 10 mM 3-AT indicated a positive interaction.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "A Chitin-induced MAPK activation in a mapkkk5 mutant (Line 1) expressing MAPKKK56xA. MAPK activity was detected using immunoblots with α-pMAPK.",
    "ncbi_link": "mapkkk5: 836819
MAPKKK5: 836819"
  },
  {
    "caption": "B Chitin-induced callose deposition in the MAPKKK56xA plant (Line 1). Seedlings were analyzed at 18 hours after treatment with 10 μM chitin. Data are means ±SD from three independent biological replicates, where each biological replicate consists of two technical replicates. The asterisks indicate statistically significant differences from the WT controls by Student's t-test (P < 0.05).",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "C Detection of MAPKKK5K375M -GFP and MAPKKK5K375M,6xA-GFP transiently expressed in Arabidopsis protoplasts.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "A PBL27 does not interact with MAPKKK5-KD:C in a yeast two-hybrid assay.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "C CERK1 does not phosphorylate the C-terminal domain of MAPKKK5 in vitro. The in vitro kinase assay was performed with recombinant proteins of GST-PBL27, MAPKKK5-C and the intracellular kinase domain of CERK1 (GST-CERK1:IC). The protein loading control was shown by staining with Coomassie Brilliant Blue. The in vitro phosphorylation reaction was carried out using [32P]γ-ATP, and the phosphorylated proteins were detected by autoradiography. Asterisks indicate artificial bands.",
    "ncbi_link": "CERK1: 821717"
  },
  {
    "caption": "D The alanine substitution mutations at the residues conserved in the activation loop of reduces the phosphorylation of PBL27 by CERK1:IC. The in vitro kinase assay was carried out with recombinant proteins of GST-PBL27K112E , GST-PBL27K112E, 3xA and CERK1-IC.",
    "ncbi_link": "PBL27: 831979"
  },
  {
    "caption": "E The kinase activity of GST-PBL273xA was analyzed by the in vitro kinase assay using [32P]γ-ATP.",
    "ncbi_link": "PBL27: 831979"
  },
  {
    "caption": "B MAPKKK5-KD phosphorylates MKK4 and MKK5 in vitro. The in vitro phosphorylation reaction was carried out using [32P]γ-ATP, and the phosphorylated proteins were detected by autoradiography.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "C MAPKKK5-KD does not phosphorylate a T224A/S230A mutant of MKK4 or a T215A/S221A mutant of MKK5. The above experiments were performed three times with similar results.",
    "ncbi_link": "MAPKKK5: 836819"
  },
  {
    "caption": "Kaplan-Meier curve of the probability of survival for 155 GBM patients with low or high MALT1 RNA level, using median cut-off, based on the TCGA RNAseq dataset.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Box and whisker plot of MALT1 mRNA expression in low-grade glioma (LGG, grades II and III) or in GBM (grade IV) (TCGA GBMLGG, RNAseq dataset) (D).",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Alternatively, MALT1 mRNA expression was plotted in non-tumor samples versus GBM samples (TCGA RNAseq dataset) (E). Each dot represents one clinical sample.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Fraction of surviving cells over time in GSC#1 and GSC#9, transduced with control (shc) or bi-cistronic GFP plasmids using two different short hairpin RNA (shMALT1 sequences, seq #1 and #2). Data are plotted as the percentage of GFP-positive cells at the day of the analysis (Dx), normalized to the starting point (Day 4 post-infection, D4).",
    "ncbi_link": "GFP: 
MALT1: 10892"
  },
  {
    "caption": "EdU incorporation (green, 2 hours) was visualized by confocal imagery in GSC#1 or by FACS in GSC#9 transfected with sic or siMALT1. In GSC#1 the percentage of EdU-positive cells was quantified. Nuclei (DAPI) are shown in blue. n> 240 cells per replicate. Scale bar: 10 μm. Data are presented as the mean + s.e.m. on 3 independent experiments.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "FACS analysis of propidium iodide (PI) staining in GSC #1 and #9 transfected with non-silencing duplexes (sic) or MALT1 siRNA duplexes (siMALT1) and analyzed 72 hours later.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Linear regression plot of in vitro limiting dilution assay (LDA) for control (shc) or shMALT1 seq#1 and seq#2 transduced GSC#9. Data are representative of n=2. Knockdown efficiency was verified at day 3 by western-blot using anti-MALT1 antibodies. GAPDH served as a loading control.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Tumorspheres per field of view (fov) were manually counted in sic or siMALT1 transfected GSC#1, #4 and #9. Data are presented as the mean + s.e.m. on 3 independent experiments.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Western-blot analysis of CYLD (full length, FL and cleaved, c'd) and MALT1 in total protein lysates from GSC#9 transfected with non-silencing RNA duplexes (sic) or MALT1 targeting duplexes (siMALT1). GAPDH served as a loading control. Densitometric analysis of c'd CYLD/FL CYLD was performed (right). Data are presented as the mean + s.e.m. on 5 independent experiments.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Western-blot analysis of CYLD and FLAG in total protein lysates from GSC#9 transfected with WT or C464A MALT1-FLAG. GAPDH served as a loading control.",
    "ncbi_link": "FLAG: 
MALT1: 10892"
  },
  {
    "caption": "Western-blot analysis of CYLD (full length FL and cleaved c'd) in total protein lysates from GSC#9 transfected with non-silencing RNA duplexes (sic) or CARD10 targeting duplexes (siCARD10 seq#1, seq#2, and seq#3). GAPDH served as a loading control. qPCR analysis confirmed the knock-down of CARD10 in GSC#9. Data are presented as the mean + s.e.m. on 3 independent experiments.",
    "ncbi_link": "CARD10: 29775"
  },
  {
    "caption": "Western-blot analysis of CYLD and BCL10 in total protein lysates from GSC#9 transfected with non-silencing RNA duplexes (sic) or BCL10 targeting duplexes (siBCL10, seq#1 and seq#3). GAPDH served as a loading control. Cell viability was measured using Cell TiterGlo luminescent assay in sic and seq#1 siBCL10-transfected cells. Data were normalized to their respective sic-treated controls and are presented as the mean + s.e.m of 3 independent experiments, in triplicate.",
    "ncbi_link": "BCL10: 8915"
  },
  {
    "caption": "Western-blot analysis was performed in total protein lysates from GSC#9 transfected with non-silencing duplexes (sic) or MALT1 targeting siRNA duplexes (siMALT1). Alternatively, western-blot analysis of LAMP2, CTSD, and MALT1 was done in total protein lysates from GSC#9 treated for 16 hours with MPZ (20 μM) or Z-VRPR-FMK (75 µM). DMSO was used as vehicle. GAPDH served as a loading control.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Confocal analysis of LAMP2 staining (red) in GSCs #1, #4, #12 treated for 16 hours with vehicle (DMSO) or MPZ (20 μM). Alternatively, GSC#9 were either treated for 16 hours with H2O or Z-VRPR-FMK (75 µM). Additionally, cells were transfected with non-silecing duplexes (sic) or MALT1 and BCL10 targeting siRNA duplexes (siMALT1 and siBCL10). Alternatively, lysotracker staining (red) was used to track for lysosomes in either GSC#9 expressing either wild-type (WT) or C464A FLAG-MALT1 (green). Scale bar: 10 μm.",
    "ncbi_link": "FLAG: 
BCL10: 8915
MALT1: 10892"
  },
  {
    "caption": "Confocal analysis of lysotracker staining (red) in GSC#9 treated for 16 hours with vehicle (DMSO) or MPZ (20 μM). Alternatively, GSC#9 were either treated for 16 hours with H2O or Z-VRPR-FMK (75 µM) (upper panel) or transfected with sic and siMALT1 (bottom panel). As indicated, number of lysotracker-positive puncta and lysotracker pixel intensity (arbitrary unit, AU) were quantified per cell. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>30. Nuclei (DAPI) are shown in blue. Scale bars: 10 μm.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Western-blot analysis of LC3B in total protein lysates from GSCs #1 and #9 at 72 hours post-transfection with sic or siMALT1, and subsequently treated 4 hours with vehicle (DMSO) or chloroquine (CQ, 20 µM). Knockdown was verified by MALT1 blotting and GAPDH served as a loading control.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "GSC#9 were transfected with LC3B reporters (wild type WT or G120A mutant, which cannot be lipidated), treated 24 hours later with vehicle (DMSO) or MPZ (20 µM) for 6 more hours. Ratios of WT/mutant luciferase signals are presented as the mean + s.e.m of 3 independent experiments.",
    "ncbi_link": "LC3B: 81631"
  },
  {
    "caption": "Confocal analysis of P62 staining (red) in GSC#9 treated for 16 hours with vehicle (DMSO) or MPZ (20 μM). Alternatively, GSC#9 were either transfected with sic or siMALT1 (middle) or treated for 16 hours with H2O or Z-VRPR-FMK (75 µM) (bottom). Quantification of P62 staining pixel intensity on GSC#9 treated for 16 hours with vehicle (DMSO or H2O), MPZ (20 µM) or Z-VRPR-FMK (75 µM) or sic and siMALT1. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>30.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "CSTD ELISA was performed on culture media from GSC#9 treated for 8 hours with vehicle (DMSO) or MPZ (20 µM). Alternatively, cells were transfected with sic or siMALT1 and analyzed 72 hours later. Data are presented as the mean + s.e.m of 3 independent experiments.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "qRT-PCR was performed on total RNA from GSC#9 treated for 4 hours with vehicle (DMSO) or MPZ (20 μM). Histograms showed changes in RNA expression of indicated targets. Data were normalized to two housekeeping genes (ACTB, HPRT1) and are presented as the mean + s.e.m of technical triplicates.",
    "ncbi_link": "ACTB: 
HPRT1: "
  },
  {
    "caption": "Western-blot analysis of LC3B, CSTD and TFEB in total protein lysates from GSC#9 transfected with non-silencing duplexes (sic) or siRNA duplexes targeting TFEB (siTFEB) and treated with vehicle (DMSO) or MPZ (20 μM) for 16 hours. GAPDH served as a loading control.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "Western-blot analysis of MALT1, p-AKT, and p-S6 in total protein lysates from GSC#9 transfected with non-silencing duplexes (sic) or MALT1 targeting siRNA duplexes (siMALT1). Total AKT and S6, as well as GAPDH served as loading controls.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "Western-blot analysis of p-S6 and FLAG in GSC#9 expressing WT or C464A MALT-FLAG. Total S6 and GAPDH served as loading controls.",
    "ncbi_link": "FLAG: 
MALT: 10892"
  },
  {
    "caption": "Confocal analysis of LAMP2 (red) and mTOR (green) staining in GSC#9 treated with vehicle (DMSO) or MPZ (20 μM), Z-VRPR-FMK (75 μM), FLU (20 μM), CHLO (20 μM), and CYA (20 μM). Alternatively, cells were transfected with sic or siMALT1. Nuclei (DAPI) are shown in blue. Arrows point to LAMP2-positive area. Scale bars: 10 μm. Quantification of mTOR colocalization score with LAMP2 is shown. The Coloc2 plug-in from ImageJ was used to measure Mander's tM1 correlation factor in LAMP2-positive ROI, using Costes threshold regression. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>10.",
    "ncbi_link": "MALT1: 10892"
  },
  {
    "caption": "(Left) Kaplan-Meier curve of the probability of survival for 155 GBM patients with low or high QKI RNA level, using median cut-off, based on the TCGA RNAseq dataset. (Right) Differential expression analysis related to either MALT1 or QKI expression highlighted a lysosomal lumen GO function. Venn diagram of overlapping lysosomal enriched protein encoding genes from this comparison showed 7 shared genes, together with 9 and 10 specific genes for MALT1 and QKI expression, respectively. (Bottom) Correlation between MALT1 and QKI expression was analyzed using The Cancer Genome Atlas (TCGA, HG-U133A dataset) on the GlioVis platform (Bowman et al, 2007). Pearson correlation factor=-0.21, p-value=0.03.",
    "ncbi_link": "MALT1: 10892
QKI: 9444"
  },
  {
    "caption": "Confocal analysis of Lysotracker (green) or FLAG (red) in GSC#9 overexpressing either empty vector (mock) or FLAG-QKI. Scale bars: 10 μm. Nuclei (DAPI) are shown in blue.",
    "ncbi_link": "FLAG: 
QKI: 9444"
  },
  {
    "caption": "Confocal analysis of LAMP2 (green) or FLAG (red) in GSC#9 transfected with either empty vector (mock) or FLAG-QKI. Scale bars: 10 μm. Nuclei (DAPI) are shown in blue. Quantification of LAMP2 staining pixel intensity on GSC#9 transfected with mock and FLAG-QKI. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>15.",
    "ncbi_link": "FLAG: 
QKI: 9444"
  },
  {
    "caption": "Confocal analysis of mTOR (green) or FLAG (red) in GSC#9 transfected with either empty vector (mock) or Flag-QKI. Nuclei (DAPI) are shown in blue. Scale bars: 10 μm.",
    "ncbi_link": "Flag: 
QKI: 9444"
  },
  {
    "caption": "GSC#1 were transfected with either empty vector (mock) or FLAG-QKI. Total protein lysates were processed for western-blots against p-S6 and FLAG. Total S6 served as a loading control.",
    "ncbi_link": "FLAG: 
QKI: 9444"
  },
  {
    "caption": "Fraction of surviving cells over time in GSCs #1 and #9, transduced with empty vector (mock) or FLAG-QKI bi-cistronic GFP plasmids. Data are plotted as the percentage of GFP-positive cells at the day of the analysis (Dx), normalized to the starting point (Day 4 post-infection, D4). Data are representative of n=3.",
    "ncbi_link": "FLAG: 
GFP: 
QKI: 9444"
  },
  {
    "caption": "GSC#9 transfected with non-silencing RNA duplexes (sic) or QKI targeting siRNA duplexes (siQKI) were treated for 16 hours with vehicle (DMSO) or MPZ (10 μM). Total protein lysates were processed for western-blots against LAMP2, CTSD, QKI, and LC3B expression, as indicated. GAPDH served as a loading control.",
    "ncbi_link": "QKI: 9444"
  },
  {
    "caption": "Confocal analysis of mTOR (green) and LAMP2 (red) in GSC#9 transfected with sic or siQKI, and treated for 16 hours with vehicle (DMSO) or MPZ (20 μM). Nuclei (DAPI) are shown in blue. Scale bars: 10 μm. Quantification of mTOR colocalization score with LAMP2 is shown. The Coloc2 plug-in from ImageJ was used to measure Mander's tM1 correlation factor in LAMP2-positive ROI, using Costes threshold regression. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>10.",
    "ncbi_link": "QKI: 9444"
  },
  {
    "caption": "GSC#9 transfected with non-silencing RNA duplexes (sic) or QKI targeting siRNA duplexes (siQKI) were treated for 1 hour with vehicle (DMSO) or MPZ (20 μM). Total protein lysates were processed for western-blots against QKI and p-S6. TUBULIN and Total S6 served as loading controls.",
    "ncbi_link": "QKI: 9444"
  },
  {
    "caption": "FACS analysis of EdU staining was performed on GSC#9 cells transfected with non-silencing RNA duplexes (sic, pink), QKI targeting siRNA duplexes (siQKI, light purple), MALT1 targeting siRNA duplexes (siMALT1, blue) or double transfected with siQKI and siMALT1 (purple).",
    "ncbi_link": "MALT1: 10892
QKI: 9444"
  },
  {
    "caption": "FACS analysis of propidium iodide (PI) staining in GSC#9 transfected with non-silencing RNA duplexes (sic), QKI targeting siRNA duplexes (siQKI), MALT1 targeting siRNA duplexes (siMALT1) or double transfected with siQKI and siMALT1 and analyzed 72 hours later. Percentage of PI-positive cells normalized to vehicle treated controls are presented as the mean + s.e.m. on 3 independent experiments.",
    "ncbi_link": "MALT1: 10892
QKI: 9444"
  },
  {
    "caption": "(F) Effect of ND-011992 on the OCR of M. smegmatis IMVs using the Oroboros O2k fluorespirometer. IMVs OCR from the parental strain (green triangles), ∆cydAB knockout (blue circles), and ∆cydAB complemented with M. tuberculosis CydABDC+ (red squares) energized with NADH were determined. Q203 was used at 1 μM. 100% OCR was defined as the OCR of the untreated samples for each strain.",
    "ncbi_link": "cydAB: 45744747///45744748"
  },
  {
    "caption": "(A) Differential gene expression analysis of H37Rv treated with Q203, ND-011992, or combination (H37Rv-Combo), and ∆cydAB treated with Q203 compared to untreated controls. The log2-fold differences in gene expression of various conditions relative to the untreated control is indicated using a sliding scale where higher expression is reflected in red and lower expression is reflected in blue, with a midpoint signifying no difference in white.",
    "ncbi_link": "cydAB: 885446///885510"
  },
  {
    "caption": "(C) Absence of the Cyt-bcc:aa3 sensitized H37Rv to ND-011992. M. tuberculosis H37Rv wildtype (Blue circles), ∆ctaE-qcrCAB (red squares) and complemented strain (green triangles) were treated with ND-011992. Growth inhibitory potency (MIC50) was recorded after 2 to 3 weeks of incubation.",
    "ncbi_link": "aa3: 
ctaE: 887425
qcrCAB: 887400///888420///888737"
  },
  {
    "caption": "(D) The reduced minus oxidized difference spectrum of M. smegmatis ΔqcrCAB inverted membrane vesicles (IMVs). The green line represents the spectrum without treatment, while the blue line represents the spectrum of the IMVs in the presence of 10 μM ND-011992.",
    "ncbi_link": "qcrCAB: "
  },
  {
    "caption": "(D) Fluctuation analysis in M. tuberculosis H37Rv. M. tuberculosis ΔcydAB was plated on 7H10 containing 100 nM Q203 (red). Parental H37Rv was plated on 7H10 with 100 nM Q203 and 6 µM ND-011992 or 2 µg/mL rifampicin (blue). The corresponding values of the median frequency of resistance is indicated in the graph.",
    "ncbi_link": "cydAB: 885446///885510"
  },
  {
    "caption": "(A) Primary hippocampal neurons (DIV6+3) were transfected with shRNA targeting TDP-43 (shTDP) or control (shCtrl) together with GFP-RAB11 to visualize trafficking of recycling endosomes (RE). At least four dendrite segments per neuron were live imaged at 5 Hz for 1 minute to analyze recycling endosome transport. Representative dendrite segments and kymographs of GFP-RAB11 vesicle movement. Quantitative analysis of vesicle motility (B) and total number (C) from kymographs.",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(D) iPSC-derived human neurons were transduced with shRNA targeting human TDP-43 (shTDP) or control (shCtrl) seven days after thawing for three days. TDP-43 levels were analyzed by quantitative RT-PCR. Expression was normalized to the housekeeping gene YWHAZ and PGK1.",
    "ncbi_link": "PGK1: 
YWHAZ: 
TDP-43: 23435"
  },
  {
    "caption": "(A) Primary hippocampal neurons (DIV6+4) were transduced with shRNA targeting TDP-43 or a control together with tagRFP (not depicted). Representative images of neurons subjected to Alexa-transferrin (Alexa-Tf) for 20 min (pulse) and chased for 0, 20 or 60 min in complete media. Scale bar represents 100 µm. (B) Quantification of labeled cellular Alexa-Tf normalized to cell area (using tagRFP) after chase period. At least ten images per condition were analyzed per experiment in three independent experiments.",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(A) Primary hippocampal neurons (DIV6+4) were transfected with myc-tagged TDP-43 wild-type or a mutant lacking the nuclear localization signal (ΔNLS) or an empty vector control. Immunostaining with the indicated antibodies and DAPI to label nuclei. Scale bar represents 50 µm.",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(B) Primary hippocampal neurons (DIV6+3) were transfected with either TDP-43 wild-type, TDP-43ΔNLS or an empty vector control together with GFP-RAB11 to visualize recycling endosomes and analyzed as in Figure 1. Quantitative analysis of recycling endosome movement (C) and vesicle number (D).",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(C-E) Primary hippocampal neurons (DIV6+4) were transduced with lentivirus expressing shRNA targeting TDP-43 or a control. Immunoblots with the indicated antibodies (C). Quantification of VPS4B and TDP-43 protein level using densitometry (n = 4). Expression was normalized to the housekeeping gene β-actin (D).",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(C-E) Primary hippocampal neurons (DIV6+4) were transduced with lentivirus expressing shRNA targeting TDP-43 or a control. VPS4B mRNA level were analyzed by quantitative RT-PCR. Expression was normalized to the housekeeping genes YWHAZ and PGK1 (E).",
    "ncbi_link": "PGK1: 
YWHAZ: 
TDP-43: 298648
VPS4B: 360834"
  },
  {
    "caption": "(G) iPSC-derived human neurons were transduced with shRNA targeting human TDP-43 (shTDP) or control (shCtrl) seven days after thawing for three days. VPS4B levels were analyzed by quantitative RT-PCR. Expression was normalized to the housekeeping gene YWHAZ and PGK1 (n = 3).",
    "ncbi_link": "PGK1: 
YWHAZ: 
TDP-43: 23435
VPS4B: 9525"
  },
  {
    "caption": "(A-B) Luciferase assay to analyze transcriptional regulation of VPS4B by TDP-43. (B) HEK293 cells were transfected with shRNAs targeting human TDP-43, a control shRNA, TDP-43 wild-type or empty vector control together with the luciferase reporter containing the rat VPS4B promoter. VPS4B promoter-driven renilla luciferase activity was normalized to TK promoter-driven firefly luciferase. Quantification from six independent experiments.",
    "ncbi_link": "firefly: 
renilla: 
TDP-43: 23435
VPS4B: 360834"
  },
  {
    "caption": "(C-D) ChIP assay to analyze binding of TDP-43 to VPS4B promoter region in rat cortical neurons, HEK293 cells and human brain tissue. PCR reaction from input, negative control and TDP-43 immunoprecipitates. Signal intensities from at least three independent experiments for each condition were quantified by densitometry and depicted as percent of input.",
    "ncbi_link": "VPS4B: 360834"
  },
  {
    "caption": "(A) Primary hippocampal neurons (DIV6+3) were transfected with either VPS4B or an empty vector control together with GFP-RAB11 to visualize recycling endosomes. Neurons were imaged as in Figure 1 to analyze recycling endosome transport. Quantitative analysis of vesicle motility (B) and number (C) from kymographs (n = 4).",
    "ncbi_link": "VPS4B: 360834"
  },
  {
    "caption": "(D) Primary hippocampal neurons (DIV6+3) were transfected with the indicated combinations of shRNA targeting TDP-43, VPS4B and control together with GFP-RAB11 and imaged as in Figure 1A. Quantitative analysis of vesicle motility (E) and number (F) from kymographs (n=3).",
    "ncbi_link": "TDP-43: 298648
VPS4B: 360834"
  },
  {
    "caption": "(A) Primary hippocampal neurons (DIV6+4) were transduced with shRNA targeting TDP-43 (shTDP) or control (shCtrl) and surface expression levels of glycoproteins was analyzed by metabolic labeling followed by surface biotinylation and subsequent streptavidin purification. Volcano plot depicts proteins that are significantly (p < 0.01, t-test, Benjamini-Hochberg, FDR: 0.05) decreased or increased on the cell surface in three independent experiments with two technical replicates. For full dataset see Table EV2.",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "(F) Primary hippocampal neurons (DIV6+4) were transduced with shTDP or shCtrl. Gene expression was analyzed by quantitative RT-PCR normalized to the housekeeping genes YWHAZ and GAPDH (n=3)",
    "ncbi_link": "GAPDH: 
YWHAZ: "
  },
  {
    "caption": "Primary hippocampal neurons (DIV6+4) were cotransfected with shTDP and GFP to visualize neuron morphology. Dendritic morphology from at least 23 neurons per condition per experiment was quantified by Sholl analysis and statistically evaluated using two-way ANOVA with Bonferroni's (B, D) or Tukey's (F, H) post-test. Scale bar represents 100 µm. (A, B) TDP-43 knockdown (DIV6+5) significantly reduces dendrite branching compared to control: at 25, 37.5 and 87.5 µm radius p < 0.05, at 50 µm p < 0.01 and from 62.5 to 75 µm p < 0.001.",
    "ncbi_link": "TDP-43: 298648"
  },
  {
    "caption": "Primary hippocampal neurons (DIV6+4) were cotransfected with VPS4B or appropriate controls and GFP to visualize neuron morphology. Dendritic morphology from at least 23 neurons per condition per experiment was quantified by Sholl analysis and statistically evaluated using two-way ANOVA with Bonferroni's (B, D) or Tukey's (F, H) post-test. Scale bar represents 100 µm. (C, D) VPS4B transfection (DIV6+4) significantly reduces dendrite complexity: at 25 µm radius p < 0.05, from 37.5 to 75 µm p < 0.001 and from 87.5 to 100 µm p < 0.01.",
    "ncbi_link": "VPS4B: 360834"
  },
  {
    "caption": "Primary hippocampal neurons (DIV6+4) were cotransfected with shTDP or appropriate controls and GFP to visualize neuron morphology. Dendritic morphology from at least 23 neurons per condition per experiment was quantified by Sholl analysis and statistically evaluated using two-way ANOVA with Bonferroni's (B, D) or Tukey's (F, H) post-test. Scale bar represents 100 µm. (G, H) Transfection of the indicated combinations of shCtrl, shTDP, ErbB4 or vector control (DIV6+5). shCtrl + Ctrl vs. shTDP + Ctrl: from 25 to 75 µm radius p < 0.001, at 87 and 112.5 µm p < 0.01 and at 100 µm p < 0.05. shTDP + Ctrl vs. shTDP + ErbB4: from 25 to 100 µm radius p < 0.001, at 112.5 µm p < 0.01. shCtrl + Ctrl vs. shTDP + ErbB4: no significant differences.",
    "ncbi_link": "ErbB4: 59323"
  },
  {
    "caption": "C qRT-PCR-validation of HSATIII knockdown. The graph shows the qRT-PCR level of HSATIII RNAs in control and HSATIII knockdown cells under three conditions: 37°C, 42°C for 2 h, and thermal stress followed by recovery at 37°C for 1 h (Recovery). Expression levels were calculated as ratios to GAPDH mRNA and were normalized to the levels in control cells under thermal stress conditions (42°C for 2 h). Data are shown as the mean±SD (n=3). HSATIII RNAs ratios (%) are indicated.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Validation of HSATIII target introns by qRT-PCR. The graphs show the relative amounts of the intron-retaining (IR) (upper) and spliced (lower) forms in control and HSATIII knockdown cells under three conditions: 37°C (normal), 42°C for 2 h (thermal stress), and thermal stress followed by recovery at 37°C for 1 h. Expression levels were calculated as the ratio of each RNA to GAPDH mRNA and were normalized to the levels in control cells under normal conditions (37°C). Data are shown as the mean±SD (n=3); *p<0.05 (Sidak's multiple comparison test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "B Nuclear localization of the intron-retaining RNAs. The relative amounts of intron-retaining RNAs in the nuclear and cytoplasmic fractions were quantified by qRT-PCR and are represented as the ratio (% of the total). GAPDH mRNA and U1 snRNA were used as cytoplasmic and nuclear controls, respectively. Data are shown as the mean±SD (n=3).",
    "ncbi_link": "GAPDH: 
U1 snRNA: "
  },
  {
    "caption": "D, E The levels of HSATIII target introns in newly synthesized RNAs within 1 h after thermal stress removal, as determined by qRT-PCR. The graphs show the changes in the expression levels of the intron-retaining (IR) (D) and spliced (E) forms. Expression levels were calculated as the ratio of each RNA to GAPDH mRNA and were normalized to the level in the control cells. Data are shown as the mean±SD (n=3); *p<0.05 (multiple t-test modified by Holm-Sidak's method).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "A Splicing isoforms of the CLK1 pre-mRNA. The retained introns are indicated by red lines. An asterisk indicates the position of the premature termination codon in the nonsense-mediated mRNA decay-targeted isoform. B Time course analysis of the splicing pattern of CLK1 pre-mRNAs in control and HSATIII knockdown (HSATIII KD) cells by semi-quantitative RT-PCR. Arrows indicate the positions of PCR primers. The GAPDH mRNA was used as an internal control. C Quantification of the data shown in (B). Data are shown as the mean±SD (n=3); *p<0.05 (Sidak's multiple comparison test). ",
    "ncbi_link": "GAPDH: 
CLK1: 1195"
  },
  {
    "caption": "F Time course analysis of the splicing pattern of Chinese hamster Clk1 pre-mRNAs in control (CHO) and CHO (His9) cells by semi-quantitative RT-PCR. Arrows indicate the positions of PCR primers. The GAPDH mRNA was used as an internal control.",
    "ncbi_link": "GAPDH: 
Clk1: 100758582"
  },
  {
    "caption": "Time course analysis of the splicing pattern of Chinese hamster Clk1 pre-mRNAs in control (CHO) and CHO (His9) cells by semi-quantitative RT-PCR. Arrows indicate the positions of PCR primers. The GAPDH mRNA was used as an internal control. G Quantification of the data shown in (F). Data are shown as the mean±SD (n=3); *p<0.05 (Sidak's multiple comparison test).",
    "ncbi_link": "GAPDH: 
Clk1: 100758582"
  },
  {
    "caption": "B RT-PCR validation of the specific precipitation of HSATIII by ChIRP. The NEAT1 ncRNA and GAPDH mRNA were used as negative controls. Input: 100%.",
    "ncbi_link": "GAPDH: 
NEAT1: "
  },
  {
    "caption": "Specific interaction of HSATIII with CLK1 proteins during stress recovery. HSATIII-ChIRP/western blotting was performed using HeLa cells expressing FLAG-CLK1 WT or the KR mutant. FLAG-tagged CLK1 and SRSF9 were detected by western blotting using an anti-FLAG and an anti-SRSF9 antibody, respectively. HSATIII was detected by ChIRP followed by RT-PCR. Input: 1% for western blotting, 100% for RT-PCR.",
    "ncbi_link": "CLK1: "
  },
  {
    "caption": "Dependency of SRSF9 on the interaction of CLK1 (G) with HSATIII. HSATIII-ChIRP was performed using control and SRSF9-depleted cells expressing FLAG-CLK1 proteins (42°C for 2 h and recovery for 1 h at 37°C). Input: 1%. Graphs represent coprecipitation ratios of FLAG-CLK1 proteins to HSATIII in the control and SRSF9-depleted cells.",
    "ncbi_link": "SRSF9: 8683"
  },
  {
    "caption": "H Dependency of SRSF9 on the interaction of CLK1∆C (H) with HSATIII. HSATIII-ChIRP was performed using control and SRSF9-depleted cells expressing FLAG-CLK1 proteins (42°C for 2 h and recovery for 1 h at 37°C). Input: 1%. Graphs represent coprecipitation ratios of FLAG-CLK1 proteins to HSATIII in the control and SRSF9-depleted cells.",
    "ncbi_link": "SRSF9: 8683"
  },
  {
    "caption": "A, B Validation of the effect of SRSF9 on retention/splicing of HSATIII target introns by qRT-PCR. The relative expression levels of intron-retaining (IR) forms (A) and spliced forms (B) of newly transcribed RNAs during the recovery period are shown. Expression levels were calculated as the ratio of each RNA to GAPDH mRNA and were normalized to the control.",
    "ncbi_link": "GAPDH: 
SRSF9: 8683"
  },
  {
    "caption": "C, D Time course analysis of the splicing patterns of CLK1 and TAF1D intron-retaining RNAs in control and HSATIII knockdown cells by semi-quantitative RT-PCR. Arrows indicate the positions of primers for RT-PCR. GAPDH mRNA was used as an internal control. The experiment was performed in triplicate. Quantification of the data shown in (C),",
    "ncbi_link": "GAPDH: 
CLK1: 1195
TAF1D: 79101"
  },
  {
    "caption": "G The diagrams show the domain structures of wild-type (WT) and mutant (mut) SRSF9, in which all SR/SP dipeptides were replaced by AR/AP. FLAG-SRSF9-WT and FLAG-SRSF9-mut were extracted from transfected HeLa cells under normal (37°C) and thermal stress (42°C for 2 h) conditions, separated in a Phos-tag gel, and detected by western blot using an anti-FLAG antibody. The arrowhead indicates the thermal stress-induced de-phosphorylated form of FLAG-SRSF9-WT.",
    "ncbi_link": "SRSF9: "
  },
  {
    "caption": "The role of phosphorylation of SRSF9 on splicing of the TAF1D (H) splicing reporter plasmid was transfected into HeLa cells along with a siRNA (control or SRSF9-specific) and a siRNA-resistant SRSF9-WT or SRSF9-mut expression plasmid (or pEGFP-C1 vector as the empty vehicle (-)) 48 h before the assay. Semi-quantitative RT-PCR analyses revealed the splicing patterns of the reporter RNAs purified from the thermal stress-exposed cells (42°C for 2 h and 37°C for 1 h). The positions of the PCR primers are indicated by arrows. Graphs represent the relative changes in the spliced/unspliced ratios, normalized to the control sample with control siRNA and empty plasmid (-).",
    "ncbi_link": "EGFP: 
SRSF9: 8683
TAF1D: 79101"
  },
  {
    "caption": "I The role of phosphorylation of SRSF9 on splicing of the DNAJB9 (I) reporters. Each splicing reporter plasmid was transfected into HeLa cells along with a siRNA (control or SRSF9-specific) and a siRNA-resistant SRSF9-WT or SRSF9-mut expression plasmid (or pEGFP-C1 vector as the empty vehicle (-)) 48 h before the assay. Semi-quantitative RT-PCR analyses revealed the splicing patterns of the reporter RNAs purified from the thermal stress-exposed cells (42°C for 2 h and 37°C for 1 h). The positions of the PCR primers are indicated by arrows. Graphs represent the relative changes in the spliced/unspliced ratios, normalized to the control sample with control siRNA and empty plasmid (-).",
    "ncbi_link": "EGFP: 
DNAJB9: 4189
SRSF9: 8683"
  },
  {
    "caption": "(a) Identification of biomarkers modulated upon VCP silencing. HeLa, HCT116 and U2OS cells were treated with the indicated siRNA oligonucleotides for 72 h. Protein cell extracts were resolved by SDS-PAGE, and filters were probed with the indicated antibodies. The extent of biomarker modulation correlated with the efficiency of silencing (oligo 4 versus pool). VCP silencing determined stabilization of cyclin E; induction of the endoplasmic reticulum chaperone GRP78, CHOP transcription factor and its downstream target GADD-34; conversion of the autophagy regulator ATG8/light chain 3 (LC3B) from the free to the lipidated form; activation of the effector caspase-3; and cleavage of the caspase target PARP-1. A graphical representation of the cell cycle distribution (percentage of cells) obtained from the cell cycle analysis (Supplementary Fig. 3b) is reported at the bottom of each sample. C, control; NT, nontargeting oligo; P, oligonucleotide pool.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(b) Effect of VCP silencing on cell growth. HeLa, HCT116 and U2OS cells were treated for 72 h with different VCP siRNA oligonucleotides and cell number was determined using a Coulter Counter (data represent mean values of two experiments).",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(c) Combination of VCP siRNA with standard-of-care therapeutics. HCT116 cells were treated for 24 h with siRNA to VCP and then were subjected to dose-response analysis with a variety of chemotherapeutic agents.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(a) Activity of VCP inhibitors NMS-249 and NMS-873 on wild-type VCP and mutants. Data represent mean values of at least three independent experiments.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(c) Binding of the EDA-ADP-ATTO 590 probe to wild-type (WT) VCP and the K615V and N616F mutants in the presence of NMS-249. Minor differences in the mP values are due to the use of different enzyme batches.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(d) Binding of the EDA-ADP-ATTO 590 probe to wild-type VCP and Walker A mutants in the presence of NMS-249. Data shown are representative results of one of three independent experiments: each determination was done in triplicate, data points denote the average value, and error bars represent s.d.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(c) High-content analysis of poly-Ub and CHOP induction upon treatment with VCP inhibitors. HeLa cells were treated with increasing doses of the indicated compounds. Cells were then fixed and immunostained with the indicated antibodies. Cell numbers and mean fluorescence intensity (MFI) were determined using the ArrayScan platform. Data were collected in triplicate (n = 3), and error bars represent s.d. AU, arbitrary units.",
    "ncbi_link": "VCP: 7415"
  },
  {
    "caption": "(A) Comparative expression during murine pre-implantation embryo development of Dppa2 (red), Dppa4 (blue), Dux (black), and Zscan4c (ZGA marker, green). Each dot represents the average value of single-cell RNA-seq",
    "ncbi_link": "Dppa2: 73703
Dppa4: 73693
Dux: 664783
Zscan4c: 245109"
  },
  {
    "caption": "(C) Sashimi plot representing coverage on the Dppa4 gene of an RNA sequencing analysis of murine zygotes, early 2C, mid 2C and late 2C Arcs depict splicing events, and numbers their relative frequency (i.e. reads across junctions).",
    "ncbi_link": "Dppa4: 73693"
  },
  {
    "caption": "(A) Average expression of Dppa2 and Dppa4 in a single-cell RNA-seq analysis of mESCs sorted for expression of both Tomato and GFP reporters driven by MERVL and Zscan4 promoters, respectively, and the double-negative population.",
    "ncbi_link": "GFP: 
Tomato: 
Dppa2: 73703
Dppa4: 73693
Zscan4: 245109"
  },
  {
    "caption": "(B) Fraction of GFP+ cells in mESCs carrying a MERVL-GFP reporter and depleted of Dppa2 or Dppa4 using shRNAs specific to the transcripts or a control. Bars represent the average, error bars the SD; n = 3. ** p ≤ 0.01, *** p ≤ 0.001, unpaired t-test.",
    "ncbi_link": "GFP: 
Dppa2: 73703
Dppa4: 73693"
  },
  {
    "caption": "(C) Dppa2, Dppa4, Dux and Zscan4 gene expression in mESCs carrying a MERVL-GFP reporter and depleted of Dppa2 or Dppa4 using shRNAs specific to the transcripts or a control. Expression was normalized to Actb. Bars represent the average, error bars the SD; n = 3. ** p ≤ 0.01, *** p ≤ 0.001, unpaired t-test.",
    "ncbi_link": "GFP: 
Actb: 11461
Dppa2: 73703
Dppa4: 73693
Dux: 664783
Zscan4: 245109"
  },
  {
    "caption": "RNA-seq analysis of WT and Dppa2 (D) KO mESC clones. The dot plot displays the average gene expression of three independent clones from each cell type; n = 3.",
    "ncbi_link": "Dppa2: 73703"
  },
  {
    "caption": "RNA-seq analysis of WT and Dppa4 (E) KO mESC clones. The dot plot displays the average gene expression of three independent clones from each cell type; n = 3.",
    "ncbi_link": "Dppa4: 73693"
  },
  {
    "caption": "(F) Comparative expression by qPCR of Dux, two downstream targets of DUX (Zscan4 and Tdpoz4), and two DUX-independent targets of DPPA2 and DPPA4 (Mael and Tdrd1) in mESCs depleted of endogenous DPPA2 and DPPA4 and overexpressing ectopically DUX or GFP as a control. Expression was normalized to Actb. Bars represent the average, error bars the SD; n = 3",
    "ncbi_link": "GFP: 
Actb: 11461
DPPA2: 73703
DPPA4: 73693
Dux: 664783
DUX: 664783
Mael: 98558
Tdpoz4: 399675
Tdrd1: 83561
Zscan4: 245109"
  },
  {
    "caption": "(H) Comparative expression of DUX-dependent, DPPA2 and DPPA4-dependent, and the rest of the genes in mESCs sorted for expression of both Tomato and GFP reporters driven by MERVL and Zscan4 promoters, respectively, and the double-negative population (unpaired t-test).",
    "ncbi_link": "GFP: 
Tomato: 
DPPA2: 73703
DPPA4: 73693
DUX: 664783
Zscan4: 245109"
  },
  {
    "caption": "(A) Comparative expression by qPCR of Dux, two downstream targets of DUX (Zscan4 and Tdpoz4), and three targets of DPPA2 and DPPA4 independent of DUX (Mael, Tdrd1, Prex2) in mESCs depleted of endogenous DPPA2 and DPPA4 and overexpressing ectopically DPPA2, DPPA4 or GFP as a control Expression was normalized to Actb. Bars represent the average, error bars the SD; n = 3. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, unpaired t-test.",
    "ncbi_link": "GFP: 
Actb: 11461
DPPA2: 73703
DPPA4: 73693
Dux: 664783
DUX: 664783
Mael: 98558
Prex2: 109294
Tdpoz4: 399675
Tdrd1: 83561
Zscan4: 245109"
  },
  {
    "caption": "(B) Average coverage normalized for sequencing depth of the ChIP-seq signal of DPPA2, DPPA4 or DPPA4 truncated of the SAP domain overexpressed in mESCs in a window of 500bp around the Dux gene (n=2). Total input (TI) is shown in gray. Peaks over the Dux gene were called in DPPA2, DPPA4 and DPPA4ΔSAP ChIP-seq.",
    "ncbi_link": "DPPA2: 73703
DPPA4: 73693
Dux: 664783"
  },
  {
    "caption": "(C) Heatmap showing the distribution of DUX, DPPA2, DPPA4 and DPPA4ΔSAP coverage in a ± 5kb window around the TSS of DUX-dependent, DPPA2 and DPPA4-dependent and random genes in mESCs.",
    "ncbi_link": "DPPA2: 73703
DPPA4: 73693
DUX: 664783"
  },
  {
    "caption": "(D) Boxplot/Jitterplot representing the percentage of GC nucleotide contents in the peaks from DPPA2, DPPA4 and DUX ChIP, and in a random shuffle of peaks.",
    "ncbi_link": "DPPA2: 73703
DPPA4: 73693
DUX: 664783"
  },
  {
    "caption": "Total expression of transposable element subfamilies in (A) Dppa2 KO compared to WT mESC clones.",
    "ncbi_link": "Dppa2: 73703"
  },
  {
    "caption": "Total expression of transposable element subfamilies in (B) Dppa4 KO compared to WT mESC clones.",
    "ncbi_link": "Dppa4: 73693"
  },
  {
    "caption": "(C) RNA-seq analysis of MERVL-int, L1Md_A and L1Md_T in mESCs sorted for expression of both Tomato and GFP reporters driven by MERVL and Zscan4 promoters, respectively, and the double-negative population.",
    "ncbi_link": "GFP: 
Tomato: 
Zscan4: 245109"
  },
  {
    "caption": "(D) Heatmap displaying the enrichment of DUX, DPPA2, DPPA4 and DPPA4ΔSAP binding at different transposable element families. Every subfamily enriched (pval < 0.05) in at least one DPPA2, DPPA4 or DPPA4ΔSAP replicate are shown.",
    "ncbi_link": "DPPA2: 73703
DPPA4: 73693
DUX: 664783"
  },
  {
    "caption": "(E) MSA plot of DPPA2, DPPA4 and DPPA4ΔSAP ChIP-seq in mESCs showing enrichment over L1Md_A, L1Md_T and MERVL-int sequences. Gaps are in grey and sequences in white with overlap of color-coded ChIP-seq signals. Upper plot shows average coverage of the signal over the aligned TEs.",
    "ncbi_link": "DPPA2: 73703
DPPA4: 73693"
  },
  {
    "caption": "(C) qRT-PCR expression of endogenous repeats following shRNA-mediated KAP1 depletion in NTERA-2 cells. Results were normalized to β2 microglobulin (B2M). KAP1 expression levels were verified by qRT-PCR and Western blot. A representative experiment of 2 experiments is shown. Two-tailed unpaired t tests were done (HERVK14C_2 p-value = 0.002300).",
    "ncbi_link": "B2M: 
β2 microglobulin: 
KAP1: 10155"
  },
  {
    "caption": "(D qRT-PCR expression of endogenous repeats following KAP1 knockout in HeLa Results were normalized to B2M. KAP1 expression levels were verified by qRT-PCR and Western blot. Two-tailed unpaired t tests were done and p-values are: HERVK14C_1: 0.0017, HERVK14C_2: 0.0044, SVA D VNTR: 0.0243 Clones 8, 12 and 15 (from D) were selected for mRNA-sequencing.",
    "ncbi_link": "B2M: 
KAP1: 10155"
  },
  {
    "caption": "E) qRT-PCR expression of endogenous repeats following KAP1 knockout in 293T cells Results were normalized to B2M. KAP1 expression levels were verified by qRT-PCR and Western blot. For (E), we found that clone I (also treated with KAP1 sgRNA) retained KAP1 protein expression (E, right panel) so we only used clones II, III and IV to explore phenotype (E, left panel), which represented validated KAP1 knockouts. Two-tailed unpaired t tests were done and p-values are: (E) HERVK14C_2: <0.0001.",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "(F) qRT-PCR expression of endogenous repeats following shRNA-mediated KAP1 depletion in PBMCs (day 6 post-transduction). Results were normalized to B2M. All error bars show standard deviation (SD). All numbers above bars depict fold changes compared to control cells (to one decimal place).",
    "ncbi_link": "B2M: 
KAP1: 10155"
  },
  {
    "caption": "(A) Boxplots showing repeats significantly upregulated (>2 fold where p=<0.05 using DESeq2) in knockout (N=3) compared to wildtype (N=3) HeLa cells based on mRNA-sequencing data. P values = 0.0174 (HERV-S), 0.0047 (HERV-K14C), 0.00013 (HERV-T LTR6B) and 1.90E-06 (HERV-T HERVS71). HERV-T and HERV-S but not HERVK14C also reached significance when only adjusted p-values were considered, where differences are compared to the whole of repBase. KAP1 binding (ENCODE data) is shown in Fig S1A. All numbers above bars depict fold changes compared to control cells (to one decimal place).",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "(B) NTERA-2 cells were transduced with either an empty vector (WT) or the same vector containing an shRNA against KAP1 (KD) prior to puromycin selection and transduction with increasing doses of GFP reporter vectors. GFP expression was analysed 72 hours post reporter transduction. A representative experiment of 2 experiments is shown. Two-tailed unpaired t test p-values: PBS-LTR-GFP: 0.0148; PBSChr15-LTR-GFP: 0.0377",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "(C) The same as (B) except that here KAP1 wildtype (WT) and knockout (KO) 293T cells were used. P-values: PBS-LTR-GFP: 0.0044; PBSChr15-LTR-GFP: 0.0077.",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "(D) PBMCs were transduced with increasing doses of GFP reporter vectors (vectors were normalized to the same number of infectious units after titering them on permissive cells), left plot. Vectors were integrated at similar levels as measured by GFP Taqman qPCR, right plot. A 293T cell line with a single vector copy integrant (PGK-GFP) was used as a control to estimate the absolute copy numbers. A representative experiment of 3 experiments is shown here. Two-tailed unpaired t test p-value 0.0288 (dose 3). Error bars show SD.",
    "ncbi_link": "PGK: "
  },
  {
    "caption": "(A) qRT-PCR expression of endogenous repeats (left) and ISGs (right) following shRNA-mediated KAP1 depletion in HeLa cells (day 6 post transduction), normalized to B2M and GAPDH respectively. n=2 and two-tailed unpaired t test p-values are: HERVK14C: 0.025, 0.003; SVA VNTR: 0.00027, 0.01; ISG56: 0.002; CCL5: 0.007, 0.00003; CXCL10: 0.0008; Mxa: 0.011; IKba: 0.008, 0.01. See also Fig S2AB.",
    "ncbi_link": "B2M: 
GAPDH: 
CCL5: 6352
CXCL10: 3627
ISG56: 3434
Mxa: 4599
IKba: 4792
KAP1: 10155"
  },
  {
    "caption": "(B) qRT-PCR expression of endogenous repeats (left) and ISGs (right) following 5-AZA treatment of HeLa cells and PBMCs (day 6 post transduction). A representative experiment of two is shown in each case. Two-tailed unpaired t tests were performed. HeLa cell p-values: ISG56: 0.005; CCL5: 0.0006; CXCL10: 0.0007; Mxa: 0.0001; IFNb: 0.02. For repeat expression (left panel), p values not available as N=2. PBMC p-values: HERVK14C: 0.1; SVA D VNTR: 0.003; ISG56: 0.001; CCL5: 0.012; CXCL10: 0.012; Mxa: 0.02; IKba: 0.08. Results were normalized to GAPDH and B2M (GAPDH results shown). See also Fig S2C for results in 293T cells. All error bars show SD.",
    "ncbi_link": "B2M: 
GAPDH: 
CCL5: 6352
CXCL10: 3627
ISG56: 3434
IFNb: 3456
Mxa: 4599
IKba: 4792"
  },
  {
    "caption": "(C) DNA methylation at endogenous SVAs was measured over 18 CpGs in the stated treatment groups (day 5 post transductions, or day 2 post 5-AZA treatment). Each point represents the average methylation state of one sequence with at least 10 sequences analyzed per group. Mann-Whitney tests were performed to compare shControl to shKAP1 (p=0.6593) and DMSO to 5-AZA (0.0027). 5-AZA was added to all experiments at 7uM. All numbers above bars depict fold changes compared to control cells (to one decimal place).",
    "ncbi_link": "KAP1: 10155"
  },
  {
    "caption": "(B) 293T cells were transduced with the stated shRNAs and cells harvested 4 days after puro selection for Western Blot to verify KAP1 and SETDB1-depletion (left) and ChIP (right). Cell numbers were normalized per treatment group before sonication and IPs were performed in triplicate. Results show IP relative to total input and GAPDH normalized. IgG control IPs gave only background enrichments shown. One representative experiment of two is shown. Unpaired t tests were performed. P values: ZNF239: KAP1, 0.0292; SETDB1, 0.0137; HERVK14C_1: KAP1, 0.0227; SETDB1, 0.0082; HERVK14C_2: SETDB1, 0.0462; SVA D VNTR, SETDB1, 0.0064. The inlay shows qRTPCR expression analysis of HERVK14C in the same experiment, normalized to B2M or GAPDH as stated. All error bars show SD.",
    "ncbi_link": "B2M: 
GAPDH: 
SETDB1: 9869
KAP1: 10155
ZNF239: 8187"
  },
  {
    "caption": "(D) An IFIT1 promoter-based Luciferase reporter THP-1 cell line was used or 293T cells or HeLa cells transduced with an IFN-β promoter-based Luciferase reporter. These cell lines were transduced with an shKAP1 or shControl vector or a vFLIP-expressing vector and luciferase measured 6 days later. Error bars show SD. Unpaired t tests were used to compare shControl to shKAP1 samples: p values = 0.122 (THP-1), 0.0001 (HeLa), 0.0001 (293T cells).",
    "ncbi_link": "vFLIP: 
IFIT1: 3434
IFN-β: 3456
KAP1: 10155"
  },
  {
    "caption": "(E) WT, STING KO and MAVS KO THP-1 cells were verified by Licor blot.",
    "ncbi_link": "MAVS: 57506
STING: 340061"
  },
  {
    "caption": "(F) Cells from (E) were untreated or transduced with shControl or shKAP1 vectors and Luciferase read over time (left). Cells were also treated with control stimulants (right). Results show the average Luciferase secreted over two time points (days 5 and 6 for the left plot and days 1 and 2 for the right plot) with all error bars showing SEM. HT-DNA: herring testis DNA.",
    "ncbi_link": "herring testis DNA: 
KAP1: 10155"
  },
  {
    "caption": "Immunofluorescence staining of apoE44 (n=3) and apoE23 (n=2) genotyped iNPH patient right frontal cortex biopsy samples Two representative microscopy images from six separate images show: (A) Colocalization of (red) apoE44 and (green) FH in the presence of (white) Aβ plaques. Scale bar = 50 μm. (B) Colocalization of (red) apoE23 and (green) FH around brain capillaries. The blue nuclei were detected using DAPI staining. (C) Colocalization of (red) apoE44 and (green) FH in the presence of (white) Aβ plaques from a biopsy sample obtained from an iNPH patient diagnosed with Alzheimer's clinical syndrome (ACS). Colocalization of apoE on Aβ is shown with an arrow. The negative staining control is shown. (D) ApoE-FH colocalization analysis of all detected colocalized foci in six microscope images from the apoE44 (n=3) and apoE23 (n=2) genotyped iNPH patient biopsy samples. Six microscope images from Alzheimer's clinical syndrome (ACS) biopsy sample are included in the apoE44 dataset (red dots).",
    "ncbi_link": "apoE23: 348
apoE44: 348"
  },
  {
    "caption": "(B) Comparison of mRNA transcripts (two individual samples obtained from three times repeated experiments) and MS1 intensities (from 8 apoE44/apoE43 and 9 apoE33/23 carriers) between genes or proteins that showed differential expression in vitro (Fig. 5B) and in vivo.",
    "ncbi_link": "apoE33: 348
apoE43: 348
apoE44: 348"
  },
  {
    "caption": "(D) (left) Combined analysis of complement activation markers C3, C4, CFH and Clusterin obtained from the detected MS1 spectra between samples from apoE44 (n=3), apoE43 (n=5), apoE33 (n=7) and apoE23 (n=2) carriers (four markers/patient). (center) Combined analysis of complement activation markers C3, C4, CFH and Clusterin obtained from the detected MS1 spectra between samples that were positive (n=10) or negative (n=7) for Aβ pathology (four markers/patient). (right) Expression levels of Phosphodiesterase A control, showing similar expression levels in frontal cortex, between samples from apoE44 (n=3), apoE43 (n=5), apoE33 (n=7) and apoE23 (n=2) carriers The data were normalized against neutral apoE33 samples with no apoE association.",
    "ncbi_link": "apoE: 348
apoE23: 348
apoE33: 348
apoE43: 348
apoE44: 348"
  },
  {
    "caption": "(e) HEK293 cells expressing GFP-tagged LRRK2 and transduced with lentivirus control (Ctr) or carrying shRNA against LAMP-2A (L2A(−)), incubated or not with NL for 12 h and immunoblotted for the indicated proteins.",
    "ncbi_link": "LAMP-2A: 16784"
  },
  {
    "caption": "(f) Immunoblots for LRRK2 and LAMP-2A of homogenates and lysosome-enriched fractions isolated from control fibroblasts (Ctr) or fibroblasts stably interfered for LAMP-2A (L2A(−)), maintained in the presence or absence of serum. Actin and LAMP-1 (L-1) are shown as loading controls of homogenate and lysosomes, respectively. All values are mean + s.e.m.; *P 0.05, unpaired t-test. Full-length blots and gels in Supplementary Figure 12.",
    "ncbi_link": "LAMP-2A: 16784"
  },
  {
    "caption": "(a) Top: immunoblot for GFP of tet-on HEK293 cells expressing GFP-tagged WT or G/S LRRK2 pulsed 24 h with doxycycline and, 48 h later (no longer undergoing de novo synthesis), incubated without additions (−) or with 20 mM NH4Cl and 100 μM leupeptin (NL), 5 μM MG132 (MG) or 10 mM 3MA. Bottom: percentage inhibition (n = 3 independent experiments).",
    "ncbi_link": "tet: 
LRRK2: 120892"
  },
  {
    "caption": "(a) Top: immunoblot for GFP of tet-on HEK293 cells expressing GFP-tagged WT or G/S LRRK2 pulsed 24 h with doxycycline and, 48 h later (no longer undergoing de novo synthesis), (b) Same cells as in a, untreated (Ctr) or treated with RNA interference for LAMP-2A (L2A(−)), pulsed as in a, sequentially collected and immunoblotted. Top left panels: representative immunoblots for GFP. Actin is shown as a loading control. Bottom left panels, quantification, corrected by levels of knockdown and loading control (n = 3 or 4 independent experiments). Top right: immunoblot for LAMP-2A. Bottom right: percentage of LRRK2 degraded per hour in the same samples.",
    "ncbi_link": "tet: 
LAMP-2A: 3920
LRRK2: 120892"
  },
  {
    "caption": "(c) Binding, association and uptake calculated from quantification of LRRK2 in immunoblots of lysosomes from starved rat livers, untreated or pretreated with protease inhibitors (PI) and incubated with WT or G/S LRRK2. Inset: representative immunoblot (n = 9 independent experiments).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(d) Association of GAPDH (5 μg) to starved rat liver lysosomes in the presence of increasing concentrations of WT or G/S LRRK2. Inset: representative immunoblot n = 4-6.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(e,f) Binding of WT and G/S LRRK2 to lysosomes in the presence of GAPDH (e) or RNase A (f). Top: representative immunoblots. Bottom: lysosome-bound LRRK2 expressed as a multiple of the amount bound when added alone. Trends of mean values (n = 2 independent experiments); error bars indicate range.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(h,i) Rat brain lysosomes incubated as in d and e, respectively. Left: representative immunoblots. Right: quantifications (n = 3 or 4 independent experiments). All values expressed as mean + s.e.m.; differences with untreated samples (*) and between WT LRRK2 and G/S LRRK2 (§) were significant at P 0.05; n.s., not significant; ANOVA and Bonferroni test. Full-length blots and gels in Supplementary Figure 12.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(a) Proteolysis in HEK293 cells stably transfected with an empty plasmid (Ctr) or plasmids expressing WT or G/S LRRK2 under the control of a tet promoter, treated with doxycycline to activate protein expression and then labeled with [3H]leucine for 48 h. After extensive washing, protein degradation at the indicated times was measured, in cells maintained either in the presence (+) or absence (-) of serum, as the amount of acid-precipitable radioactivity (amino acids and small peptides) released into the media. Values are expressed as percentage of radioactivity in proteins (acid precipitable) at time 0 (n = 4 independent experiments, each in triplicate).",
    "ncbi_link": "tet: 
LRRK2: 120892"
  },
  {
    "caption": "(c) Cultured ventral midbrain dopaminergic neurons from Ctr and from WT-LRRK2 and G/S-LRRK2 transgenic mice, transduced with the same reporter as in b and co-stained with antibody to tyrosine hydroxylase (TH). Nuclei are highlighted with DAPI (4′,6-diamidino-2-phenylindole) in blue. Left: representative images. Right: average number of puncta per cell in >50 TH-positive cells. Scale bars, 10 μm. All values are mean + s.e.m.; differences with Ctr (*) and between WT LRRK2 and G/S LRRK2 (§) were significant at P 0.05; unpaired t-test in a and ANOVA and Bonferroni test in b,c.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(a) Immunoblots of rat liver lysosomes incubated with WT or G/S LRRK2 alone or with 1 mM GTP and/or GAPDH. Duplicate samples are shown. Bottom: quantification of lysosome-bound LRRK2 expressed as a multiple of the amount bound without additions (n = 6 independent experiments).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(b) Effect of kinase inhibitor on WT, G/S, or the kinase-dead mutant D/A LRRK2 incubated with rat liver lysosomes in presence or absence of GAPDH (5 μg). Right: quantification expressed as a multiple of the association without additions (n = 3-5 independent experiments).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(c,d) Transient transfection of HEK293 cells with the myc- or GFP-tagged LRRK2 constructs indicated at top left in c. Full, full length; M, KFERQ-like motifs (M1-M8). (c) Binding to GST-hsc70. Left, representative immunoblots; input lanes, one-tenth of input material. NT, non-transfected cells. Immunoblot for hsc70 is shown as loading control. Top right: quantification of LRRK2 bound to hsc70. Where indicated, samples were also incubated with RNase A to compete the KFERQ-mediated binding of hsc70 (n = 3 or 4 independent experiments). (d) Coimmunoprecipitation (IP) of hsc70 with anti-myc or anti-GFP in the same cells. Inputs (Inp), one-quarter of starting volume.",
    "ncbi_link": "hsc70: 3312
LRRK2: 120892"
  },
  {
    "caption": "(f) Co-IP of LAMP-2A with anti-LRRK2 in lysosomes incubated with WT or G/S LRRK2. Inp, one-quarter of starting sample; IgG, immunoglobulin G. Values: LAMP-2A recovered in the IP (IP L2A) corrected for the amount of LRRK2 pulled down and expressed as a multiple of WT value.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(g,h) Duplicate LAMP-2A immunoblots of rat liver lysosomes incubated alone (−) or with WT or G/S LRRK2 (g) or with lysosomes from control (Ctr) or from WT-LRRK2 or G/S-LRRK2 transgenic mice (h) and subjected to blue native electrophoresis. Arrow, 700-kDa multimeric complex. All values are mean + s.e.m.; differences compared to none or untreated (*) or to WT or full-length protein (§) were significant at P 0.05; unpaired t-test in a and ANOVA and Bonferroni test in b,c. Full-length blots and gels in Supplementary Figure 12.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(a) Top: LRRK2 immunoblot of rat liver lysosomes incubated with WT, G/S, D/A (kinase-dead), I/T or R/C mutant LRRK2, alone or in the presence of protease inhibitors (PI). Input lanes, one-quarter of input material. Bottom: quantification of binding and uptake (calculated as in Fig. 2b; n = 4 or 5 independent experiments).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(c) Top: coimmunoprecipitation (co-IP) of LAMP-2A (L2A) with anti-LRRK2 from lysosomes incubated with LRRK2proteins as in a. Co-immunoprecipitated fractions were immunoblotted for LAMP-2A and LRRK2. Input: immunoblot for LAMP-2A before the affinity purification. Bottom: amount of LAMP-2A coimmunoprecipitated, expressed as a multiple of the value with WT LRRK2 (n = 3 or 4 independent experiments).",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(d) Co-IP of LAMP-2A with anti-GFP in tet-on HEK293 cells expressing GFP-LRRK2 proteins and pulsed for 24 h with doxycycline. Inputs (Inp), one-quarter of material added.",
    "ncbi_link": "tet: "
  },
  {
    "caption": "(a) α-syn immunoblot of rat liver lysosomes incubated with WT or mutant (A53T) α-syn alone (−) or with WT LRRK2 or G/S LRRK2. Inp, input; Mon, monomers. Right: quantification of α-syn oligomers, expressed as a multiple of amounts in samples without LRRK2 (n = 4 or 5 independent experiments).",
    "ncbi_link": "LRRK2: 120892
α-syn: 6622"
  },
  {
    "caption": "(e) Ventral midbraindopaminergic neuronal cultures from control (Ctr) or WT-LRRK2 or G/S-LRRK2 transgenic mice untreated or treated with RNAi for LAMP-2A (L2A(−)). (f) Colocalization between α-syn and total LAMP-2 from cells in e (n > 50 tyrosine hydroxylase (TH)-positive neurons). Total LAMP-2 is not reduced in L2A knockdown cells because LAMP-2B is upregulated.",
    "ncbi_link": "LAMP-2A: 16784
LRRK2: 120892"
  },
  {
    "caption": "(i,j) iPSC lines as in g, differentiated for 30 or 75 d and untreated or treated with RNAi for LAMP-2A. (i) Immunofluorescence for LAMP-2A, α-syn and GFP in LAMP-2A-RNAi iPSC lines differentiated for 30 d. Bottom: higher magnifications of boxed areas. (j) Percentage of TH+ cells showing cytoplasmic accumulation of α-syn. n ≥ 2 experiments using two control and two LRRK2 iPSC lines (n > 70 and n > 150 TH+ cells in Ctr and LRRK2, respectively). Scale bars, 10 μm. All values are mean + s.e.m. Differences from WT or control (*) or between control or knockdown cells (§) are significant at P 0.05; unpaired t-test in a,h and ANOVA and Bonferroni test in f,j. Full-length blots and gels in Supplementary Figure 12.",
    "ncbi_link": "LAMP-2A: 3920"
  },
  {
    "caption": "(A-C) Excision of endogenous Hi in cmt23 (A), drm12 (B), and ddcc (C) mutant backgrounds when HiTG is segregated away. Plants with * and ** were used for WGBS, and the results of those with ** were used for the analysis shown in Figures.",
    "ncbi_link": "cmt2: 827640
drm1: 831390"
  },
  {
    "caption": "(D) Excision of endogenous Hi in mutant backgrounds of epigenetic regulators. drm12: drm1 drm2 double mutant, ddc: drm1 drm2 cmt3 triple mutant, cmt23: cmt2 cmt3 double mutant, and ddcc: drm1 drm2 cmt2 cmt3 quadruple mutant. Histone acetyltransferase HDA6/RTS1 is reported as important for silencing of TEs, and TEs activated in hda6 mutant are shared with those activated in met1",
    "ncbi_link": "cmt2: 827640
cmt3: 843313
drm1: 831390
drm2: 831315
hda6: 836431
HDA6: 836431
RTS1: 836431
met1: 834975"
  },
  {
    "caption": "(A-C) Patterns of DNA methylation in endogenous Hi (A), AT2TE05755 (B), and AT2TE06955 (C) in the drm12 mutant background. '(-HiTG)' indicates that HiTG was segregated. Vertical dashed lines indicate termini of TEs.",
    "ncbi_link": "AT2TE05755: 3768055
AT2TE06955: 814971
drm1: 831390"
  },
  {
    "caption": "(A) Patterns of DNA methylation in flanking regions of VANC21 targets when HiTG was segregated in drm12 (left) and cmt23 (right) mutant background. Grey dashed lines indicate the points of VANC targets.",
    "ncbi_link": "VANC21: 816880
cmt2: 827640
drm1: 831390"
  },
  {
    "caption": "(C) Patterns of DNA methylation around VANC21 (left), VANC6 (middle), and VANC1 (right) targets.",
    "ncbi_link": "VANC1: 841076
VANC21: 816880
VANC6: 3769791"
  },
  {
    "caption": "(C) Hi excision in F2 plants obtained from met1 x GK345. Genotyping results of MET1 and Hi loci are also shown. a-h indicate individuals who are analyzed for their DNA methylation status in (D).",
    "ncbi_link": "met1: 834975
MET1: 834975"
  },
  {
    "caption": "(A) Expression of VANB21 (At2g23490) and VANC21 (At2g23480) measured by RT‒qPCR. The values were normalized to the expression levels in the ddm1 mutant. For each genotype, the average values and standard deviations of the three technical replicates are shown. Note that we could not detect the expression of VANC21 in drm12 (-HiTG), although endogenous Hi retained mobility (Fig. 6C). This finding can likely be explained by the expression of VANA21, a transposase of VANDAL21, but we failed to compare the expression levels of this gene because of its very low expression level.",
    "ncbi_link": "VANC21: 816880
At2g23480: 816880
VANA21: 816880
VANDAL21: 816880
VANB21: 816881
At2g23490: 816881
ddm1: 836808
drm1: 831390"
  },
  {
    "caption": "(B) DNA methylation status of coding and noncoding regions of five VANDAL21 TEs The average values and standard deviations for each region are shown. One-way ANOVA with Tukey's multiple comparisons test was used to determine the significant differences (p<0.01).",
    "ncbi_link": "VANDAL21: 816880"
  },
  {
    "caption": "(A) Immunoblot analysis of caspase-1 and gasdermin D in WT or Nlrp3-/- unprimed and LPS-primed BMDMs left untreated [Medium alone (Med.)] or assessed 20 hr after stimulation with the supernatant (Sup.) of or assessed 20 hr after infected with WT C. perfringens (WT C. per), ΔpfoA C. perfringens (ΔpfoA), Δcpa C. perfringens (Δcpa, lacking lecithinase) or ΔpfoAΔcpa C. perfringens (ΔpfoAΔcpa) at MOI 100.",
    "ncbi_link": "cpa: 69447757
lecithinase: 69447757
Nlrp3: 216799
pfoA: 69447922"
  },
  {
    "caption": "(A) Concentration of IL-18 in the serum of WT mice, 8 hr after intraperitoneal infection with 4 × 108 colony-forming units (CFUs) of C. perfringens (WT C. per, n = 14), ΔpfoA C. perfringens (ΔpfoA, n = 13), Δcpa C. perfringens (Δcpa, n = 11) or ΔpfoAΔcpa C. perfringens (ΔpfoAΔcpa, n = 12). (B) Concentration of IL-18 in the peritoneal fluid of WT mice, 4 hr after intraperitoneal infection with 4 × 108 CFUs of C. perfringens (WT C. per, n = 14), ΔpfoA C. perfringens (ΔpfoA, n = 15), Δcpa C. perfringens (Δcpa, n = 17) or ΔpfoAΔcpa C. perfringens (ΔpfoAΔcpa, n = 14). (C) Concentration of IL-18 in the serum of WT mice (n = 10), Nlrp3-/- mice (n = 9), and Casp1/11-/- mice (n = 19), 6 hr after intraperitoneal infection with 1 × 108 CFUs of C. perfringens. (D) Concentration of IL-18 in the peritoneal fluid of WT mice (n = 10), Nlrp3-/- mice (n = 9), and Casp1/11-/- mice (n = 19), 3 hr after intraperitoneal infection as described in C.",
    "ncbi_link": "Casp1: 12362
cpa: 69447757
Nlrp3: 216799
pfoA: 69447922"
  },
  {
    "caption": "(G) Survival of WT (n = 19), Nlrp3-/- (n = 26) and Casp1-/- (n = 10) mice, after intraperitoneal administration of 0.312 Units/ml of lecithinase (Lec.).",
    "ncbi_link": "Casp1: 12362
Nlrp3: 216799"
  },
  {
    "caption": "(I) Release of IL-1β (top), IL-18 (middle) and death (bottom) of WT or Ninj1-/- BMDMs left untreated or LPS-primed and assessed for a range of time points after stimulation with lecithinase (Lec.) or 16 hr after transfection with LPS (LPS trans.).",
    "ncbi_link": "Ninj1: 18081"
  },
  {
    "caption": "(J) Immunoblot analysis of caspase-1, gasdermin D and NINJ1 of WT or Ninj1-/- BMDMs left untreated or LPS-primed and assessed 3 hr after stimulation with lecithinase (Lec.) or 16 hr after transfection with LPS (LPS trans.).",
    "ncbi_link": "Ninj1: 18081"
  },
  {
    "caption": "H Western blot  confirming no YAP  and TAZ  expression in two independent (#1 and #2) YAP/TAZ  double knockout (Y/T DKO) clones.",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "I Relative expression  levels of YAP/TAZ  target genes CYR61  and CTGF  in HEK293A  WT and Y/T DKO clones in response to cyclic 0.1Hz 200mbar hydrostatic pressure. Data from six independent experiments Error bars represent mean ± SD. Kruskal-Wallis test with Dunn's post hoc. **p=0.0661 (WT CYR61), ***p= 0.0001 (WT CTGF), p=0.3924 (Y/T DKO#1 CYR61), p=0.4616 (Y/T DKO#1 CTGF), p>0.999 (Y/T DKO#2 CYR61), p=0.0782 (Y/T DKO#2 CTGF).",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
CTGF: 1265
TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "J CYR61  and CTGF gene expression levels induced by  hydrostatic pressure in (I) of Y/T DKO #1 and #2 normalised to WT. Kruskal-Wallis test with Dunn's post hoc. *p=0.0259 (Y/T DKO#1 CYR61), **p=0.0007 (Y/T DKO#1 CTGF), *p=0.0155 (Y/T DKO#2 CYR61), ***p<0.001 (Y/T DKO#2 CTGF).",
    "ncbi_link": "CYR61: 3491
CTGF: 1265"
  },
  {
    "caption": "B Comparison of cell volume  of WT and  LATS1/2 DKO clones at steady state obtained using DHM. Each dot represents a single cell. Data from three independent experiments. Error bars represent mean ± 95% CI. Kruskal-Wallis test with Dunn's post-hoc. **p=0.0018 (WT vs LATS1/2 DKO #1), ***p<0.001 (WT vs LATS1/2 DKO #2), p=0.0557 (LATS1/2 DKO #1 vs #2).",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "C Comparison of cell volume  of WT and MST1/2 DKO at steady state obtained using DHM. Each dot represents a single cell. Data from three independent experiments. Error bars represent mean ± 95% CI. Mann-Whitney U test. p=0.2731.",
    "ncbi_link": "MST1: 4485"
  },
  {
    "caption": "D HEK293A NF2  KO cells response to 100mbar cyclic hydrostatic pressure. Each dot represents a single cell and Error bars represent mean ± 95% CI. Data pooled from three independent experiments. Mann-Whitney U test. p=0.4072.",
    "ncbi_link": "NF2: 4771"
  },
  {
    "caption": "E Comparison of cell volume of WT and TEAD  KO clones at steady state obtained using DHM. Each dot represents a single cell. Data from three independent experiments. Error bars represent mean ± 95% CI. Kruskal-Wallis test with Dunn's post-hoc. p>0.9999 for all comparisons.",
    "ncbi_link": "TEAD: 7004///7005///8463///7003"
  },
  {
    "caption": "K Representative immunofluorescence  images showing MYC-tagged YAP  expression in WT YAP  re-expressing cells and S94A mutant YAP  re-expressing cells compared to Y/T DKO vector control. 95% were positive for expression of YAP  or YAP  mutant. Scale bar = 20µm.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "L  Western blot showing total YAP, TAZ  and CYR61  levels in WT YAP  and S94A mutant YAP  re-expressing cells compared to WT and Y/T DKO vector control.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "M Average change in cell volume in response to  hydrostatic pressure in WT YAP  and S94A mutant YAP  re-expressing cells relative to Y/T DKO. Each dot represents a single cell. Error bars represent mean ± 95% CI. Data pooled from three independent experiments. Kruskal-Wallis test with Dunn's post hoc. p<0.001 (vector vs. WT YAP), p=0.4912 (vector vs. S94A YAP), p=0.0327",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "N Average change in cell volume in response to 100mbar cyclic  hydrostatic pressure  in WT and TEAD  KO clones. Each dot represents a single cell. Data pooled from three independent experiments. Error bars represent mean ± 95% CI. Kruskal-Wallis test with Dunn's post hoc. ***p < 0.001 (for both comparisons), p>0.9999 (TEAD  KO #1 vs #2).",
    "ncbi_link": "TEAD: 7003///8463///7005///7004"
  },
  {
    "caption": "C Representative immunofluorescence  images showing Phalloidin-labelled actin  (red) and Hoechst  (blue) in Latrunculin B (LatB) (0.5µM) or Cytochalasin D (CytD) (2µM)-treated HEK293A  cells compared to control across Hippo pathway genome-edited cells as shown. Scale bar = 20μm. D Average change in  cell volume obtained by DHM  in response to hydrostatic pressure with 2µM Cytochalasin D  (CytD) treatment in WT, Y/T DKO and LATS1/2 DKO cells. Each dot represents a single cell and error bars represent mean ± 95% CI. Data pooled from four independent experiments. Kruskal-Wallis test with Dunn's post hoc. **p=0.0044 (WT con vs CytD), p*=0.0409 (Y/T DKO con vs CytD), p>0.9999 (LATS1/2 DKO con vs CytD), ***p=0.0003 (WT con vs Y/T DKO con), ***p<0.001 (WT con vs Y/T DKO CytD), ***p<0.001 (Y/T DKO CytD  vs LATS1/2 DKO CytD). E Fold difference in average change in  cell volume in response to dynamic hydrostatic pressure from (H) normalised against untreated cells. Each dot represents a single cell and error bars are 95% CI. Mann-Whitney U test. **p=0.0069 (WT vs. Y/T DKO), **p=0.0031 (WT vs LATS1/2 DKO). F Average change in cell volume in response to hydrostatic pressure with 0.5µM  Latrunculin B (Lat B) treatment in WT, Y/T DKO and LATS1/2 DKO cells. Each dot represents a single cell and error bars represent mean ± 95% CI. Data pooled from four independent experiments. Kruskal-Wallis test with Dunn's post hoc. ***p<0.001 (all comparisons), p=0.0972 (LATS/12 DKO con vs LatB), *p=0.0216 (Y/T DKO LatB  vs LATS1/2 DKO LatB). G Fold difference in average change in cell volume in response to cyclic 0.1Hz 100mbar  hydrostatic pressure from (F) normalised against control. Each dot represents a single cell and error bars represent mean ± 95% CI. Mann-Whitney U test. p=0.1472 (WT vs. Y/T DKO), **p=0.0015 (WT vs LATS1/2 DKO).",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "A Confocal IF  images labelled with Hoechst  (Blue) and internalised Transferrin   (Trf). Cells were allowed to internalize  for ten minutes, fixed and acid stripped to remove surface bound Trf. Hydrostatic pressure (H.P.) promotes transferrin  uptake in WT and LATS1/2 DKO cells. Scale bar = 20µm. B Quantification of transferrin  uptake in WT, Y/T DKO and LATS1/2 DKO cells treated with  hydrostatic pressure  compared to steady state. Each dot represents a single cell and error bars represent mean ± 95% CI. Data from four independent experiments. Kruskal-Wallis test with Dunn's post hoc. Steady-state statistical analysis is shown in blue, transferrin  uptake induced by pressure is shown in black. ***p<0.001 (WT con vs +H.P.), p=0.2375 (Y/T DKO con vs +H.P.), ***p<0.001 (LATS1/2 DKO con vs +H.P.), p=0.2764 (WT con vs Y/T DKO con), p=0.0808 (WT con vs LATS1/2 DKO con), ***p=0.0004 (Y/T DKO con vs LATS1/2 DKO con).",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "C Confocal IF   images myc  tagged AP180C   (green) cells showing internalised Trf  (red) and stained  with Hoechst (blue). AP180C  inhibits transferrin uptake in WT and Y/T DKO cells. Scale bar = 20µm. D Quantification of transferrin  uptake in AP180C  positive cells compared to vector control from images as in C. Each dot represents a single cell from four independent experiments and error bars represent mean ± 95% CI. Mann-Whitney U test. ***p < 0.001 (for both comparisons).",
    "ncbi_link": "AP180C: "
  },
  {
    "caption": "E Confocal IF  images of HEK293A WT cells showing subcellular localisation  of YAP  (red) in AP180C  (green) negative and positive WT and LATS1/2 DKO cells. Cells also stained  with Hoechst (blue). F Quantification of cytoplasmic-to-nuclear  ratio of YAP  in AP180C  positive WT and LATS1/2 DKO cells compared to vector control from images as in E. Each dot represents a single cell pooled from four independent experiments. Error bars represent mean ± 95% CI. Mann-Whitney U test. ***p=0.0008 (WT), p=0.9318 (LATS1/2 DKO).",
    "ncbi_link": "LATS1: 9113"
  },
  {
    "caption": "(A) Morphological phenotypes of Wild type (WT), mkk1 mkk2 and summ3-1 mkk1 mkk2 plants. Photos were taken on three-week-old soil-grown plants.",
    "ncbi_link": "summ3: 815625
mkk1: 828713
mkk2: 829103"
  },
  {
    "caption": "(D-E) Expression of PR1 (D) and PR2 (E) in the indicated genotypes as determined by quantitative RT-PCR. Values were normalized to the expression levels of ACTIN1. The data are shown as mean ± SD (n=3) with one-way ANOVA analysis and Tukey test (P < 0.01). Different letters indicate significant differences. The experiments were repeated three times with similar results.",
    "ncbi_link": "ACTIN1: 
PR2: 824893
PR1: 815949"
  },
  {
    "caption": "(A) Morphological phenotypes of WT, summ3-17, mekk1-1 and summ3-17 mekk1-1 plants grown on soil for three weeks.",
    "ncbi_link": "summ3: 815625
mekk1: 826409"
  },
  {
    "caption": "(B-C) Expression levels of PR1 (B) and PR2 (C) in the indicated genotypes as determined by quantitative RT-PCR. Values were normalized to the expression levels of ACTIN1. The data are shown as mean ± SD (n=3) with one-way ANOVA analysis and Tukey test (P < 0.01). Different letters indicate significant differences. The experiments were repeated three times with similar results. Two-week-old seedlings grown on half MS plates were used for assays in (B)-(C).",
    "ncbi_link": "ACTIN1: 
PR2: 824893
PR1: 815949"
  },
  {
    "caption": "(D) Morphological phenotypes of WT, mpk4-3, summ3-1 mpk4-3 and summ3-2 mpk4-3 plants. Photos were taken on three-week-old soil grown plants.",
    "ncbi_link": "summ3: 815625
mpk4: 828151"
  },
  {
    "caption": "(E-F) Expression levels of PR1 (E) and PR2 (F) in the indicated genotypes as determined by quantitative RT-PCR. Values were normalized to the expression levels of ACTIN1. The data are shown as mean ± SD (n=3) with one-way ANOVA analysis and Tukey test (P < 0.01). Different letters indicate significant differences. The experiments were repeated three times with similar results. Two-week-old seedlings grown on half MS plates were used for assays in (E)-(F).",
    "ncbi_link": "ACTIN1: 
PR2: 824893
PR1: 815949"
  },
  {
    "caption": "(A) Morphological phenotypes of transgenic plants over-expressing MEKK2-FLAG protein in WT and summ3-17 background. Line 1 and 2 express MEKK2-FLAG in WT background. Line 3-5 express MEKK2-FLAG in the summ3-17 mutant background. The photograph shows four-week-old soil grown plants. Expression of MEKK2-FLAG was detected by western blot using an anti-FLAG antibody.",
    "ncbi_link": "summ3: 815625
MEKK2: 826407"
  },
  {
    "caption": "(D-E) Expression levels of PR1 (D) and PR2 (E) in the indicated genotypes as determined by quantitative RT-PCR. Values were normalized to the expression levels of ACTIN1. The data are shown as mean ± SD (n=3) with one-way ANOVA analysis and Tukey test (P < 0.01). Different letters indicate significant differences. The experiments were repeated three times with similar results.",
    "ncbi_link": "ACTIN1: 
PR2: 824893
PR1: 815949"
  },
  {
    "caption": "(A) Quantification of luciferase activity in N. benthamiana leaves expressing CRCK3NLuc and MPK4CLuc or MPK6CLuc. Data were collected three days after infiltration. The data are shown as mean ± SD (n=8) with one-way ANOVA analysis and Tukey test (P < 0.01). Different letters indicate significant differences. The experiments were repeated twice with similar results.",
    "ncbi_link": "CRCK3: 815625
MPK4: 828151
MPK6: 818982"
  },
  {
    "caption": "(B) Phosphorylation of CRCK3G390R by MPK4. MPK4 was immunoprecipitated from wild type or MPK4::MPK4-FLAG. After incubation with [γ-32P] ATP and the immunoprecipitated MPK4-FLAG protein in protein kinase buffer, CRCK3G390R was separated by SDS-PAGE. The autoradiograph of the gel is shown in the top panel, and immunoblot analysis of MPK4-FLAG levels is shown in the bottom panel. Myelin basic protein (MBP) was used as a positive control. This experiment was repeated three times with similar results.",
    "ncbi_link": "MPK4: 828151"
  },
  {
    "caption": "(C) Western blot analysis of CRCK3-FLAG proteins in wild type and mpk4-3. Total protein was extracted from two-week-old CRCK3-FLAG transgenic plants in WT and mpk4 background grown on ½ MS medium plates. The protein extracts were treated with or without λ-PMPase phosphatase. The proteins were separated by Phos-tagTM acrylamide gel electrophoresis and CRCK-FLAG proteins were detected by western blot analysis using an anti-FLAG antibody. Similar results were obtained in two independent experiments. pCRCK3, phosphorylated CRCK3-FLAG protein.",
    "ncbi_link": "mpk4: 828151"
  },
  {
    "caption": "(D) Western blot analysis of CRCK3-FLAG and CRCK35S-5A-FLAG proteins in transgenic plants of wild type background. Total protein was extracted from two-week-old plants grown on ½ MS medium plates. The protein extracts were treated with or without λ-PMPase phosphatase. The proteins were separated by Phos-tagTM acrylamide gel electrophoresis and the FLAG-tagged proteins were detected by western blot analysis using an anti-FLAG antibody. Similar results were obtained in two independent experiments. 5S-5A stands for a change in five amino acids (S172A, S181A, S188A, S195A, S202A).",
    "ncbi_link": "CRCK3: 815625"
  },
  {
    "caption": "(A) In vivo pull-down of HA-tagged SUMM2 by FLAG-tagged CRCK3.FLAG-tagged full-length or truncated CRCK3 and HA-tagged SUMM2 proteins were transiently expressed in N. bethamiana by agro-infiltration. FLAG-tagged CRCK3 proteins were immunoprecipitated with anti-FLAG conjugated beads (Sigma) and detected by Western blot using anti-FLAG antibody. HA-tagged SUMM2 protein co-immunoprecipitated with FLAG-tagged CRCK3 was detected by Western blot using anti-HA antibody. Similar results were obtained in two independent experiments.",
    "ncbi_link": "CRCK3: 815625"
  },
  {
    "caption": "(B) In vivo pull-down of HA-tagged SUMM2 by FLAG-tagged CRCK3 kinase domain. KD represents a truncation of SUMM3 with only the kinase domain (amino acid 201-510).FLAG-tagged full-length or truncated CRCK3 and HA-tagged SUMM2 proteins were transiently expressed in N. bethamiana by agro-infiltration. FLAG-tagged CRCK3 proteins were immunoprecipitated with anti-FLAG conjugated beads (Sigma) and detected by Western blot using anti-FLAG antibody. HA-tagged SUMM2 protein co-immunoprecipitated with FLAG-tagged CRCK3 was detected by Western blot using anti-HA antibody. Similar results were obtained in two independent experiments.",
    "ncbi_link": "CRCK3: 815625"
  },
  {
    "caption": "B, Complementation analysis of DNA synthesis. Stable cell lines expressing BRPF3 resistant to the BRPF3/a siRNA and control (lacZ-V5) were siRNA transfected and analysed for EdU incorporation as in A. Error-bars, SD; n = 6 biological replicas. Two-tailed t test, ** p<10-2.",
    "ncbi_link": "lacZ: 
BRPF3: 27154"
  },
  {
    "caption": "D, Immunoprecipitation analysis of BRPF3 deletion mutants. One representative experiment out of two is shown.",
    "ncbi_link": "BRPF3: 27154"
  },
  {
    "caption": "E, Histone acetyltransferase assay (HAT) with purified BRPF1/3 complexes on free histones and mononucleosomes.",
    "ncbi_link": "BRPF1: 7862"
  },
  {
    "caption": "F, HAT assay with purified BRPF1/3 complexes on H3 peptides unmodified or acetylated (ac)/methylated (me) at K14 and K27, respectively.",
    "ncbi_link": "BRPF1: 7862"
  },
  {
    "caption": "G, Analysis of histone acetylation in BRPF3 depleted cells. (left) Western blot of siRNA treated U-2-OS cells. TSA treatment (1 hr) was included as a positive control. 2x, double amount of extract loaded in 1x. (right) H3K14 acetylation levels quantified relative to total H3. Error bars, SD; n = 3 biological replicates.",
    "ncbi_link": "BRPF3: 27154"
  },
  {
    "caption": "H, Complementation analysis of H3K14ac. Total cell extracts of siRNA treated lacZ-V5 and BRPF3-V5 (siBRPF3/a resistant) expressing cells were analysed by western blotting. One representative experiment out of four biological replicas is shown.",
    "ncbi_link": "lacZ: 
BRPF3: 27154"
  },
  {
    "caption": "G, Analysis of chromatin-bound proteins in HBO1 depleted cells as in E. One representative experiment out of two biological replicas is shown.",
    "ncbi_link": "HBO1: 11143"
  },
  {
    "caption": "A, ChIP-seq analysis of BRPF3 binding on the human genome. BRPF3 enrichment signal obtained by ChIP-seq with asynchronous (AS), synchronized (S) and released into HU (S+HU) RKO cells, on the MCM4 (left) and Lamin B2 (right) replication origins. Signals were compared to the published enrichment signals for ORC1 in HeLa cells ((Dellino et al, 2013), GSE37583), HBO1 in RKO cells (Avvakumov et al., 2012, GSE33221), and H3K14ac in IMR90 cells (GSM521881). The negative control IgG signal shown is from the S+HUchromatin.",
    "ncbi_link": "H3: 
BRPF3: 27154
HBO1: 11143
Lamin B2: 84823
MCM4: 4173"
  },
  {
    "caption": "B, Venn diagrams illustrating the overlap of genome binding sites between (top) BRPF3, HBO1 and ORC1, and (bottom) BRPF3, BRPF1/2 and ORC1 in human cells.",
    "ncbi_link": "BRPF1: 7862
BRPF3: 27154
HBO1: 11143"
  },
  {
    "caption": "C, Heatmaps of BRPF3, HBO1 and H3K14ac ChIP-seq signal on ± 5kb surrounding the TSS of genes. Genes were sorted by BRPF3 abundance from high to low. A.U. arbitrary unit.",
    "ncbi_link": "H3: 
BRPF3: 27154
HBO1: 11143"
  },
  {
    "caption": "D, Average profiles of BRPF3 and H3K14ac ChIP-seq signal on ± 2.5kb around the centre of (top) BRPF3 and (bottom) ORC1 genome binding sites.",
    "ncbi_link": "H3: 
BRPF3: 27154"
  },
  {
    "caption": "E, ChIP-qPCR analysis of H3K14ac on well-characterized replication origins. H3K14ac enrichments measured relative to IgG control are shown relative to control siRNA treated cells. Error bars, range; n= 2 biological replicas.",
    "ncbi_link": "H3: "
  },
  {
    "caption": "F, Expression levels of DNA replication factors were not altered by the lack of BRPF3. Each point represents the expression levels of a gene in control and BRPF3 depleted cells (GSE65065). Replication factors were classified as described previously (Alabert et al, 2014). Total genes (grey), DNA replication factors (colors) and BRPF3 (black) expression levels are shown. Continuous black lines mark 1.5 fold change in expression levels.",
    "ncbi_link": "BRPF3: 27154"
  },
  {
    "caption": "A, Western blot of DNA damage signalling in BRPF3 depleted cells. siRNA transfected U-2-OS cells were treated with HU for 2 h or 24 h. One representative experiment out of two biological experiments is shown.",
    "ncbi_link": "BRPF3: 27154"
  },
  {
    "caption": "(A) Assay of Tcf7l1 mRNA by RT-PCR for the first 4 days of differentiation in the presence or absence of 3 μM CH. Average and SD of three independent experiments. Day2 *p= 0.048, Day3 *p=0.036.",
    "ncbi_link": "Tcf7l1: 21415"
  },
  {
    "caption": "(C) Assay of FoxA2 mRNA by RT-PCR for the first 3 days of differentiation in the presence or absence of 3 µM CH. Average and SD of three independent experiments. **p=5x10-7.",
    "ncbi_link": "FoxA2: 15376"
  },
  {
    "caption": "(D) ChiP-seq data from a compendium of transcription factor ChIP-seq analyses (Sánchez-Castillo et al, 2015). Gene tracks represent binding of Tcf7l1 at the FoxA2, Nodal and Eomesodermin (Eomes) gene locus. Red lines indicate the regions analyzed by ChIP PCR for Tcf7l1.",
    "ncbi_link": "Eomes: 13813
Eomesodermin: 13813
FoxA2: 15376
Tcf7l1: 21415"
  },
  {
    "caption": "(E) ChIP for Tcf7l1 followed by qPCR for the regions indicated in Fig. 2D. Analysis was performed in wild-type ES cells in 2i culture conditions. Average and SD of three independent experiments. Klf2 *p=0.025, FoxA2 *p=0.050, Eomes *p=0.023.",
    "ncbi_link": "Eomes: 13813
FoxA2: 15376
Klf2: 16598
Tcf7l1: 21415"
  },
  {
    "caption": "(F) ChIP for Tcf7l1 followed by qPCR. Analysis was performed in wild-type ES cells on day 3 of differentiation in the presence or absence of 3 µM CH. Average and SD of three independent experiments. FoxA2 *p = 0.049.",
    "ncbi_link": "FoxA2: 15376
Tcf7l1: 21415"
  },
  {
    "caption": "(A) Assay of FoxA2 mRNA by RT-PCR in Tcf7l1 null cells on day 1 to 4 of differentiation without CH. Average and SD of three independent experiments.",
    "ncbi_link": "FoxA2: 15376
Tcf7l1: 21415"
  },
  {
    "caption": "(B) Gene expression analysis of endodermal associated genes by RT-PCR in control wild-type and Tcf7l1 null cells on day 4 of differentiation in the presence and absence of 3 µM CH. Average and SD of three independent experiments.",
    "ncbi_link": "Tcf7l1: 21415"
  },
  {
    "caption": "(C) FoxA2 (green) and Oct4 (red) immunostaining of Tcf7l1 null ES cells on day 4 of differentiation in the presence or absence of 3 µM CH. DAPI staining in blue.",
    "ncbi_link": "Tcf7l1: 21415"
  },
  {
    "caption": "(D) Assay of CXCR4, Hex and Sox17 mRNA by RT-PCR in control wild-type and Tcf7l1 null cells on day 6 of differentiation in the presence and absence of 3 µM CH. Average and SD of three independent experiments.",
    "ncbi_link": "CXCR4: 12767
Hex: 15242
Sox17: 20671
Tcf7l1: 21415"
  },
  {
    "caption": "(A) Assay of FoxA2 mRNA by RT-PCR in FoxA2-Tet ES cell lines 48 hr after treatment with the indicated dose of DOX. Average and SD of two independent experiments from 2 independent lines.",
    "ncbi_link": "FoxA2: 15376"
  },
  {
    "caption": "B) FoxA2 immunostaining of FoxA2-Tet ES cells 48 hr after DOX treatment. Left, no DOX control. Middle and right, 10ng/ml DOX. DAPI staining shown in blue. Right panel shows middle image without DAPI signal.",
    "ncbi_link": "FoxA2: 15376"
  },
  {
    "caption": "(C) Assay of FoxA2 and CXCR4 mRNA by RT-PCR on day 3 of differentiation with DOX at the indicated dose. Average and SD of two experiments from two independent cell lines.",
    "ncbi_link": "CXCR4: 12767
FoxA2: 15376"
  },
  {
    "caption": "(D) Assay of Sox17 mRNA by RT-PCR on day 7 of differentiation with addition of 3 µM CH and/or 10 ng/ml DOX at the indicated time points (in days). Average and SD of two independent experiments from two independent cell lines.",
    "ncbi_link": "Sox17: 20671"
  },
  {
    "caption": "(B) Assay of Tcf7l1 and FoxA2 mRNA by RT-PCR at day 2 of differentiation in the presence or absence of 3 µM CH or recombinant Wnt3a (200 ng/ml plus 500 ng/ml RSpondin1(WR)). Average and SD of three independent experiments. ** p<0.01.",
    "ncbi_link": "FoxA2: 15376
Tcf7l1: 21415"
  },
  {
    "caption": "(C) Assay of Tcf7l1 and FoxA2 mRNA by RT-PCR in Ctnnb1 null cells at day 1 and 3 of differentiation in the absence or presence of 3 µM CH. Average and SD of three independent experiments.",
    "ncbi_link": "Ctnnb1: 12387
FoxA2: 15376
Tcf7l1: 21415"
  },
  {
    "caption": "(D) Immunoblot for Tcf7l1 in Ctnnb1 null cells during the first 3 days of differentiation in the absence (-) or presence (+) of 3 µM CH. Results from two independent, clonally-derived Ctnnb1 null ES cell lines are shown. Tubulin was used as a loading control.",
    "ncbi_link": "Ctnnb1: 12387"
  },
  {
    "caption": "(A) Assay of cMyc mRNA by RT-PCR in wild-type ES cells at day 1 to 3 of differentiation. Average and SD of three independent experiments.",
    "ncbi_link": "cMyc: 17869"
  },
  {
    "caption": "C,D) Immunoblot for the destabilized form of cMyc protein (pThr58) during the first 3 days of differentiation in the absence (-) or presence (+) of 3 µM CH in wild-type and Ctnnb1 null cells respectively.",
    "ncbi_link": "Ctnnb1: 12387"
  },
  {
    "caption": "C,D) Immunoblot for the destabilized form of cMyc protein (pThr58) during the first 3 days of differentiation in the absence (-) or presence (+) of 3 µM CH in wild-type and Ctnnb1 null cells respectively.",
    "ncbi_link": "Ctnnb1: 12387"
  },
  {
    "caption": "(E) Assay of Tcf7l1 mRNA by RT-PCR in wild-type cells at day 2 of differentiation in the presence or absence of a small molecule inhibitor of cMyc (cMyc Inhibitor II; Myci). Treatment with Myc inhibitor 10058-F4 (Sigma) generated similar results (data not shown). Average and SD of three independent experiments. **p=0.0002.",
    "ncbi_link": "cMyc: 17869
Tcf7l1: 21415"
  },
  {
    "caption": "(F) Assay of Tcf7l1 and FoxA2 mRNA by RT-PCR in cMyc null/nMyc heterozygous cells (C-/-;N+/-) and floxed parental cells (cMycfl/fl;nMycfl/fl (control)) at day 3 of differentiation in the presence or absence of 3 µM CH. Average and SD of four or six independent experiments. Tcf7l1 *p=0.01, FoxA2 *p=0.034.",
    "ncbi_link": "FoxA2: 15376
cMyc: 17869
nMyc: 18109
Tcf7l1: 21415"
  },
  {
    "caption": "(G) FoxA2 immunostaining of control and cMyc null/nMyc heterozygous (cMyc-/-;nMyc+/-) cells at day 3 of differentiation in the presence of 3 µM CH.",
    "ncbi_link": "cMyc: 17869
nMyc: 18109"
  },
  {
    "caption": "(H) Assay of cMyc and Tcf7l1 mRNA by RT-PCR in cMycT58A inducible cell lines (icMycT58A) 24 hr after DOX treatment. Average of 2 independent experiments.",
    "ncbi_link": "cMyc: 17869
Tcf7l1: 21415"
  },
  {
    "caption": "(I) Assay of Tcf7l1 mRNA by RT-PCR in icMycT58A clone 1 cell line at day 3 of differentiation in the absence of 3 µM CH following cMyc induction with 10 ng/ml DOX. Average and SD of 3 independent experiments. **p=0.007.",
    "ncbi_link": "cMyc: 17869
Tcf7l1: 21415"
  },
  {
    "caption": "(J) Immunoblot for cMyc and Tcf7l1 in icMycT58A clonal cell line 1 48 hr after DOX induction at 10ng/ml.",
    "ncbi_link": "cMyc: 17869"
  },
  {
    "caption": "(B) ChIP for cMyc performed in wild-type ES cells differentiated for 2 days in the absence or presence of 3 µM CH. qPCR was carried out for the regions indicated in Fig. 7a. Average and SD for five independent experiments, *p=0.028.",
    "ncbi_link": "cMyc: 17869"
  },
  {
    "caption": "(C) ChIP for cMyc performed in wild-type ES cells differentiated for 2 days in the presence of 3 µM CH plus or minus Myc inhibitor 10058-F4. Average and SD for three independent experiments, *p=0.026.",
    "ncbi_link": "cMyc: 17869"
  },
  {
    "caption": "(D) Assay for Miz1 mRNA by RT-PCR for the first three days of differentiation in the presence or absence of 3 µM CH. Average and SD of three independent experiments.",
    "ncbi_link": "Miz1: 22642"
  },
  {
    "caption": "(E) ChIP for Miz1 or IgG control performed in E14 ES cells differentiated for 2 days in presence of 3 µM CH. qPCR was carried out for the regions indicated in Fig. 7a. Average and SD for five independent experiments, **p=0.0015.",
    "ncbi_link": "IgG: "
  },
  {
    "caption": "(C) Survival analysis of mice of the indicated genotypes; number as indicated for each genotype. No statistical difference between genotypes by Log-rank (Mantel-Cox) test. R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4).",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(E) Peripheral blood leukocyte populations (by lineage) between genotypes at day 0 and day 28. ; R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4). All BM, spleen and thymic analysis at day 28 post tamoxifen treatment",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(G) Differential analysis of leukocyte populations in the BM. R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4). All BM analysis at day 28 post tamoxifen treatment",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(H) BM erythroid cells. R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4). All BM, analysis at day 28 post tamoxifen treatment",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(J) Differential analysis of leukocyte populations in the spleen. R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4). spleen analysis at day 28 post tamoxifen treatment;",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(K) Thymic cellularity. (L) Differential analysis of thymocyte populations in the thymus. ( R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4). thymic analysis at day 28 post tamoxifen treatment",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(N) qPCR (SYBR green) based analysis of indicated gene expression in BM. Data expressed as mean +/- SEM gene expression related to Ppia expression. R26-CreERki/+ Adar1fl/+ (control; n=3) and R26-CreERki/+ Adar1fl/P195A (P195A; n=4).",
    "ncbi_link": "Adar1: 56417
Cre: 2777477
ER: 2099
R26: 14910
Ppia: 268373"
  },
  {
    "caption": "(H) survival of pups derived from breeding of a Adar1P195A/P195A to a Adar1+/- animal; number as indicated for each genotype.",
    "ncbi_link": "Adar1: 56417"
  },
  {
    "caption": "(K) survival of pups derived from breeding an Adar1P195A/- to an Adar1P195A/+ genotype; number indicated for each genotype. Inset photo: 35-day-old Adar1P195A/- male bred from Adar1P195A/P195A x Adar1+/- parents (data in Panel F); sibling 29-day-old Adar1P195A/+ and Adar1P195A/- male bred from an Adar1P195A/- x Adar1P195A/+ (data in Panel I).",
    "ncbi_link": "Adar1: 56417"
  },
  {
    "caption": "(B) survival of Adar1P195A/E861AIfih1-/- and littermates (all Ifih1-/-).",
    "ncbi_link": "Adar1: 56417
Ifih1: 71586"
  },
  {
    "caption": "(D) survival of Adar1P195A/-Ifih1-/- and littermates (all Ifih1-/-).",
    "ncbi_link": "Adar1: 56417
Ifih1: 71586"
  },
  {
    "caption": "(F) qPCR (SYBR green) analysis of Ifit1 (left) and Irf7 (right) expression on day 14 of analysis.",
    "ncbi_link": "Ifit1: 15957
Irf7: 54123"
  },
  {
    "caption": "(H) qPCR (SYBR green) of Ifit1 (left) and Irf7 (right) expression in the cell lines collected at 3 or 24 hours post-treatment with 50 or 1000 U/mL of IFNβ. No statistical difference between genotypes in Ifit1 (left) and Irf7 (right) expression.",
    "ncbi_link": "Ifit1: 15957
Irf7: 54123"
  },
  {
    "caption": "(D) Posterior confocal sections of UAS-mCD8-GFP; Ddc-Gal4 adult male brain in combination with UAS-LacZ or UAS-Myc.RNAi-1 stained with antibody to nc82 (pan-neuropil marker; magenta). Scale bars represent 50 μm.",
    "ncbi_link": "Gal4: 
LacZ: 
Ddc: 35190
Myc: 31310"
  },
  {
    "caption": "(B) Drosophila S2 cells transfected with the pUAST-HA empty vector or the pUAST-HA-Myc plasmid were co-transfected with each of the firefly luciferase reporter vector bearing the fragment shown in (A). After 48 hours, the luciferase activity was detected in each cell lysate (n = 5 times).",
    "ncbi_link": "HA: 
firefly luciferase: 116160065
Myc: 31310"
  },
  {
    "caption": "(C) Drosophila S2 cells transfected with the pUAST-HA-Myc plasmid or the empty vector were used for quantification of ChIP-PCRs (n = 4 times).",
    "ncbi_link": "HA: 
Myc: 31310"
  },
  {
    "caption": "A. Whole mount in situ hybridization (WISH) of evi1at 20 (left) and 32 (middle) hpf. evi1expression is visible in various structures of the brain, neuronal structures, the posterior pronephric duct (ppnd) and the branchial arches (ba), as well as in the VDA (ventral dorsal aorta) region. Additionally, evi1co-localizes with the endothelial marker flk1 (right).",
    "ncbi_link": "flk1: 796537
evi1: 497407"
  },
  {
    "caption": "B, C. WISH of runx1/c-myb ;in HSPCs (B), mpo in neutrophils (left) and l-plastin (right) in monocytes/macrophages (C) at 36 hpf in control (upper) and evi1 MO (lower) injected embryos.D-G. WISH of globinin erythrocytes of 6 dpf old embryos (D), of rag-1in the thymus of 5 dpf embryos (E; red asterisk), of cd41at 52 hpf (F), and gata2bat 32 hpf (G) for both control (upper) and evi1 morpholino (lower) injected embryos.H. Quantitation of results is shown for each gene, displaying the percentages of embryos with normal vs. changed expression in each condition. A Fisher´s exact test was applied to calculate statistical significance. P < 0.001 (***).",
    "ncbi_link": "gata2b: 436962
globin: 30601
cd41: 445380
l-plastin: 30583
evi1: 497407
mpo: 337514
c-myb: 30519
rag-1: 30663
runx1: 58126"
  },
  {
    "caption": "I. WISH of runx1/c-myb in HSPCs of uninjected control and UAS:mEvi1 plasmid DNA injected Tg(-1.5hsp70l:Gal4) embryos with heat-shock induction performed at 14 hpf.J. WISH of runx1/c-myb in HSPCs of uninjected control and UAS:mEvi1 mRNA in Tg(fli.1:Gal4FF;UAS:RFP) embryos, leading to endothelial-specific evi1 overexpression.K. Graph displays quantitation of results from I and J using the same method as above.",
    "ncbi_link": "fli.1: 30619
Gal4: 855828
hsp70l: 560210
Evi1: 497407
evi1: 497407
c-myb: 30519
runx1: 58126"
  },
  {
    "caption": "A. WISH of notch1b(upper) and dll4(lower) in both control (left) and evi1 MO injected embryos (right).",
    "ncbi_link": "dll4: 563920
evi1: 497407
notch1b: 794892"
  },
  {
    "caption": "B. WISH of notch1b in uninjected (left) and UAS:mEvi1 plasmid DNA injected (right) Tg(fli.1:Gal4FF;UAS:RFP) embryos resulting in endothelial-specific evi1 induction.",
    "ncbi_link": "fli.1: 30619
Gal4: 855828
evi1: 497407
Evi1: 497407
notch1b: 794892"
  },
  {
    "caption": "A. Confocal time-lapse live imaging was performed in Tg(c-myb:GFP;kdrl:mKate-CAAX) embryos from 28 to 42 hpf (Movie EV 1). Shown are three representative time-points in which the transformation from hemogenic endothelial cells to the hematopoietic fate is visible, indicated by the white arrowheads. For each time-point merged images are shown. White arrowheads denote double-positive cells.B. Cell counts of total numbers of kdrl+cmyb1+ cells \"in view\", dividing and respectively emerging HSPCs. n=10 movies from n=3 biological replicates were analyzed. A non-parametric Mann-Whitney test was used to test for statistical significance and error bars are shown as ± s.d.",
    "ncbi_link": "GFP: 
mKate: 
kdrl: 796537
c-myb: 30519"
  },
  {
    "caption": "C. Gene expression analysis of endothelial (kdrl, flt1, dab2, cdh5) and blood specific genes (c-myb, CD45, CD41, runx1) in sorted kdrl+c-myb+ cells from 34 hpf Tg(c-myb:GFP;kdrl:mKate-CAAX) embryos. Cells were isolated from 15-25 pooled embryos per sample. Three biological experiments were performed with one representative shown. Error bars indicate s.d.\u2028of three technical replicates for each representative experiment.",
    "ncbi_link": "GFP: 
mKate: 
cdh5: 445471
dab2: 404040
flt1: 544667
CD41: 445380
kdrl: 796537
c-myb: 30519
CD45: 559154
runx1: 58126"
  },
  {
    "caption": "A. WISH for runx1/c-mybin 36 hpf evi1 morphant (left) and evi1 morphant transgenic Tg(5xUAS-E1b:6xMYC-notch1a;-1.5hsp70l:Gal4) embryos (right) with global heat-shock (HS) induction at 20 hpf.B. WISH for runx1/c-myb in 36 hpf evi1 morphant (left) and evi1 morphant transgenic Tg(5xUAS-E1b:6xMYC-notch1a;cdh5:gal4ff) embryos with endothelial-specific NICD induction (right).C. WISH for runx1/c-myb in 36 hpf evi1 morphant (left) and evi1 morphant transgenic Tg(Hsp70l:vegfaa;myl7:eGFP) embryos (right) with global heat-shock induction at 20 hpf.D. WISH for runx1/c-mybin 32 hpf evi1 MO injected embryos (left) and embryos injected with both evi1 MO and capped gata2 mRNA (right).E. Quantitation of all rescue experiments. Shown are the percentages of embryos displaying normal or changed runx1/c-myb expression. A Fisher´s exact test was applied to calculate statistical significance. (n.s., not significant; p < 0.001 (***); p<0.01 (**)).",
    "ncbi_link": "eGFP: 
cdh5: 445471
Gal4: 855828
gata2: 30480
hsp70l: 560210
Hsp70l: 560210
evi1: 497407
c-myb: 30519
myl7: 30592
notch1a: 30718
runx1: 58126
vegfaa: 30682"
  },
  {
    "caption": "A. Confocal time-lapse live imaging was performed in Tg(c-myb:GFP;fli.1:UAS;Gal4:RFP) evi1 morphant embryos (top, Movie EV 2) or in Tg(c-myb:GFP;fli.1:UAS;Gal4:RFP) crossed to Tg(5xUAS-E1b:6xMYC-notch1a) embryos prior to MO injection (bottom, Movie EV 3) from 28 to 42 hpf. Shown are three representative time-points, in which the transformation from hemogenic endothelial cells to the hematopoietic fate is visible. For each time-point merged images are shown. NICD induction controlled by endothelial fli.1 (lower panel) can rescue the evi1 morphant phenotype and increases the number of HSPCs cells emerging from the VDA (arrows).B. Cell counts of emerging HSPCs in control and evi1 morphant fish with or without endothelial NICD induction. At least n=5 movies from n=3 biological replicates were analyzed. A non-parametric Mann-Whitney test was used to test for statistical significance and error bars are shown as ± s.d. (n.s., not significant, p<0.05 (*)).",
    "ncbi_link": "fli.1: 30619
Gal4: 855828
evi1: 497407
c-myb: 30519
notch1a: 30718"
  },
  {
    "caption": "A. WISH of dll4(upper) and notch1b(lower) in control injected embryos (left), evi1 morphants (middle) and evi1 morphant transgenic Tg(Hsp70l:vegfaa;myl7:eGFP) embryos at 32 hpf after heat-shock induction at 20 hpf (right).",
    "ncbi_link": "eGFP: 
dll4: 563920
Hsp70l: 560210
evi1: 497407
myl7: 30592
notch1b: 794892
vegfaa: 30682"
  },
  {
    "caption": "B, C. WISH of runx1/c-myb(B) or notch1b(C) after treatment with DMSO (left), the VEGF receptor inhibitor SU5461 (middle) and respectively SU5461 after injection of UAS:mEvi1 (inducing endothelial evi1 expression) in Tg(fli.1:Gal4FF;UAS:RFP) embryos (right).",
    "ncbi_link": "fli.1: 30619
evi1: 497407
Evi1: 497407
c-myb: 30519
notch1b: 794892
runx1: 58126"
  },
  {
    "caption": "A. Expression of runx1/c-myb in the VDA after treatment with DMSO vehicle control (left), the PI3K/AKT inhibitor Wortmannin (WM, middle) and after joined treatment with WM and enforced NICD expression via HS at 14 hpf in Tg(5xUAS-E1b:6xMYC-notch1a;-1.5hsp70l:Gal4) embryos (right). Graph displays quantitation of results. Shown are the percentages of embryos with normal or decreased runx1/c-mybexpression for each condition.",
    "ncbi_link": "Gal4: 855828
hsp70l: 560210
c-myb: 30519
notch1a: 30718
runx1: 58126"
  },
  {
    "caption": "B. Expression of notch1b after treatment with DMSO vehicle control (left) or Wortmannin (WM, middle). Graph displays quantitation of results. Shown are the percentages of embryos with normal or decreased notch1b expression for each condition.",
    "ncbi_link": "notch1b: 794892"
  },
  {
    "caption": "C. WISH for runx1/c-myb in control injected embryos (upper left), evi1 morphants (upper right) or respectively evi1 MO with myr-AKT injected embryos with HS at 14 hpf (lower right) and evi1 MO with UAS-myr-AKT injected transgenic Tg(fli.1:Gal4FFubs3; UAS:RFP)rk embryos.D. Quantitation of results from (C). Shown are the percentages of embryos with normal or decreased runx1/c-myb expression for each condition.",
    "ncbi_link": "AKT: 100149794///560549///378972///101910198
fli.1: 30619
evi1: 497407
c-myb: 30519
runx1: 58126"
  },
  {
    "caption": "E. WISH for notch1b in evi1 Morpholino injected (left) and evi1 plus UAS:myr-AKT injected transgenic Tg(fli.1:Gal4FFubs3; UAS:RFP)rk embryos (right). Graph displays quantitation of results. Shown are the percentages of embryos with normal or decreased notch1b expression for each condition.",
    "ncbi_link": "AKT: 100149794///560549///378972///101910198
fli.1: 30619
evi1: 497407
notch1b: 794892"
  },
  {
    "caption": "U2OS cells were transfected, synchronized at the G1/S-border by thymidine for 24 hours and then either released into nocodazole for 16 hours (unperturbed mitotic entry) or released for 7 hours, treated with 0.5 μM Adriamycin for one hour and after 16 hour G2 arrest were induced to recover by addition of caffeine (checkpoint recovery). Mitotic index was scored based on the percentage of Histone H3-pS10 positive DAPI-nuclei and normalized to the untransfected controls. Black diamonds indicate individual siRNA-targeted genes from the library, light grey diamonds indicate positive (Wip1-depleted) and negative (untransfected and GAPDH-depleted) controls and dark grey diamonds indicate the hits based on the two screens. Dotted lines indicate selection criteria for recovery-specific genes.",
    "ncbi_link": "GAPDH: 2597
Wip1: 8493"
  },
  {
    "caption": "D) U2OS cells were transfected with either a control siRNA or Tlk2 siRNA #3, synchronized and damaged in G2. Cells were either harvested or treated with caffeine for 8 hours before harvest and cell cycle distribution was analyzed by FACS. Percentages of cells in each quadrant are indicated.",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "E) Tlk2Δ cells were generated using CRISPR/Cas9 genome editing. Cells were synchronized in G2 by thymidine release, damaged with 0.5 μM Adriamycin for one hour. After a 16-hour G2 arrest cells were induced to recover by addition of caffeine for 8 hours and analyzed by FACS. Error bars represent SD, n=4. Statistical significance was tested using a paired two-tailed t-test (NS for P>0.05, * for P≤0.05, *** for P≤0.001).",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "F) U2TR cells stably expressing Tlk2 siRNA #3-insensitive tetracycline-inducible FLAG-Tlk2-wt or FLAG-Tlk2-D613A were thymidine synchronized and damaged in G2. Tetracycline was present form the start of the experiment where indicated.",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "C) U2OS cells were synchronized in G2 and harvested at the indicated times after induction of adriamycin-induced DNA damage with or without Tlk2-depletion. Samples were analyzed by western blotting for the indicated proteins.",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "D) U2OS cells were synchronized in G2 and damaged with 6 Gy of IR. Samples were taken at the indicated times after induction of damage with or without Tlk2-depletion. Samples were analyzed by western blot for the indicated proteins. Band signal intensity for Asf1A and Asf1B was measured and corrected for Ponceau S staining.",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "J) FLAG-Asf1A-4D inducible cells were treated as in 3I and expression was induced using doxycycline where indicated. Whiskers represent 5-95% of data points. Statistical significance was tested using an unpaired two-tailed t-test (**** for P≤0.0001).",
    "ncbi_link": "Asf1A: 25842"
  },
  {
    "caption": "B) Tlk2Δ 9.3.1 cells were treated and analyzed as in 3A. Error bars represent SD, n=3. Statistical significance was tested using a paired two-tailed t-test (NS for P>0.05, * for P≤0.05, ** for P≤0.01).",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "H) U2TR cells stably expressing Tlk2 siRNA #3-insensitive tetracycline-inducible FLAG-Tlk2-wt were thymidine synchronized, damaged in G2 and harvested 24 hours afterwards. Tetracycline was either absent (off), added from the start of the experiment (early) or for 16 hours after induction of DNA damage (late).",
    "ncbi_link": "Tlk2: 11011"
  },
  {
    "caption": "B Representative examples of GFP-labeled presynaptic boutons. Scale bars: 2.5 μm. C Quantification of presynaptic bouton density and weighted size in the mPFC  (PL and  IL). Mock: n= 57 axons from 6 mice; ZIKV: n= 63 axons from 7 mice. D Quantification of presynaptic bouton weighted size in the mPFC (PL and  IL). Mock: n= 2974  boutons  from 6 mice; ZIKV: n= 3486 boutons from 7 mice. Data information: All data were presented as mean ± SEM. *P<0.05, **P<0.01, Two-tailed unpaired t-test unless described otherwise.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "C Representative  animal tracks in  three-chamber test. D Discrimination indices of the social memory session  of three-chamber test. mCherry mock, n=8 mice;  mCherry ZIKV, n=10  mice; hM4Di ZIKV n=10 mice, mCherry mock vs. mCherry ZIKV p=0.0041; mCherry ZIKV vs. hM4Di ZIKV p=0.0115; and  mCherry mock vs. hM4Di ZIKV p=0.7076. Data information: All data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ****P < 0.0001, one-way ANOVA with Tukey post hoc test.",
    "ncbi_link": "mCherry: 
M4Di: 1132"
  },
  {
    "caption": "E Representative confocal images of  mCherry (red) and  c-Fos (green) double-labeled cells in the vHIP CA1   regions. Scale bars, 50 μm. F. Quantification of the percentage of c-fos;mCherry double positive cells out of total mCherry cells. mCherry mock, n=6 mice; mCherry ZIKV, n=4 mice; hM4Di ZIKV n=6 mice. Data information: All data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ****P < 0.0001, one-way ANOVA with Tukey post hoc test. ",
    "ncbi_link": "mCherry: 
M4Di: 1132"
  },
  {
    "caption": "(C) Figures show the presence of differentially expressed genes within the analyzed single cells. Black color indicates cells with RPKM values above 40 for Pax3, 300 for Stmn2, 200 for Slc1a3 and 100 for Mbp",
    "ncbi_link": "Mbp: 17196
Pax3: 18505
Slc1a3: 20512
Stmn2: 20257"
  },
  {
    "caption": "(B) Expression (RPKM) of Sox3 and Sox9 in NPC and GPC cultures from RNA-seq experiments. Results are represented as mean ± SEM from 3-4 experiments (n=3 for NPC and n=4 for GPC, *** equals p=4x10-5, t.test)",
    "ncbi_link": "Sox3: 20675
Sox9: 20682"
  },
  {
    "caption": "(G) Expression pattern of genes associated with group I and II loci (from Fig. 2E) within differentially expressed gene sets. Significance calculated by prop.test R, (***) P<0.001. (H) Venn diagram shows overlap between SOX3 binding in NPCs and GPCs. Bar graph shows expression pattern of genes continuously bound by SOX3 NPCs and GPCs. (I) Venn diagram shows overlap between SOX3 and SOX9 binding in GPCs. Bar graph shows expression pattern of genes co-bound by SOX3 and SOX9 in GPCs. (J) ChIP-seq peak graphics around the astrocyte gene Fgfbp3. ChIP-seq peaks are derived from three different experiments; SOX3 ChIPs in NPCs, SOX3 ChIPs in GPCs, SOX9 ChIPs in GPCs. Both ChIP-seq reads and called peak regions (underlying black lines) are shown for all data sets. Bar graphs shows the distribution of differentially expressed genes that are bound by all three factors. P-values (phyper, R) were calculated from the total number of protein coding genes in mm10 assembly (23´389)",
    "ncbi_link": "Fgfbp3: 72514"
  },
  {
    "caption": "(A) Graphical view showing SOX9 and SOX10 expression among spinal cord cells analyzed with scRNA-seq",
    "ncbi_link": "SOX10: 20665
SOX9: 20682"
  },
  {
    "caption": "(F) Expression of Nfia, Ehf and Zbtb3 among spinal cord cells analyzed with scRNA-seq. Red color indicates cells with RPKM values above 55 for Nfia, 5 for Zbtb3 and 5 for Ehf. n=3 for SOX9 and 2 for SOX3. P-values (phyper, R) were calculated from the total number of genes for mm10 (23´389)",
    "ncbi_link": "Ehf: 13661
Nfia: 18027
Zbtb3: 75291"
  },
  {
    "caption": " (A) Luc-reporter assays in P19 cells. Luc-reporters containing SOX3 and SOX9 bound CRMs around the astrocyte specific genes Fgfbp3 and Ttyh1 were strongly activated by SOX9 in synergy with NFIA; an activation that could be efficiently blocked by SOX3. No activation of these reporters could be detected with SOX10 or SOX11. (B) Luc-reporters containing SOX9 and SOX10 bound DNA-regions around the astrocyte genes Aldh1l1 and Atp1a2, which are not expressed in SOX10+ oligodendrocytes, could not be activated by SOX9 or SOX10 ",
    "ncbi_link": "Aldh1l1: 107747
Atp1a2: 98660
Fgfbp3: 72514
NFIA: 18027
SOX10: 29361
SOX11: 20666
SOX3: 20675
SOX9: 20682
Ttyh1: 57776"
  },
  {
    "caption": "(C) Luc-reporters containing SOX9 and SOX10 bound CRMs around the oligodendrocyte specific genes Plekhb1 and Mid2 were activated in an additive manner by SOX9 and SOX10. No activation could be detected with SOX11. (D) Luc-reporters containing SOX3 and SOX11 bound CRMs of the neuronal genes Tubb3 and Lhx2, which are sequentially bound by SOX3 and SOX11, could be activated by SOX11 and efficiently repressed by SOX3. No activation could be detected with SOX10",
    "ncbi_link": "Lhx2: 16870
Mid2: 23947
Plekhb1: 27276
SOX10: 29361
SOX11: 20666
SOX3: 20675
SOX9: 20682
Tubb3: 22152"
  },
  {
    "caption": "(E) Forced expression of SOX3 for 96 hrs in differentiating GPCs blocked the formation of astrocytes but not oligodendrocytes. Scale bar, 25µm. (F) Statistical view of Fig. 5E. Bars represents mean values (of 3 experiments) of cells expressing GFAP or SOX10 in GFP or Sox3-transduced cells. Error bars in figure 5 indicate standard deviation of 3-7 individual samples and three-star significance > 0.001 (t-test). (*) 0,05<P<0,01; (**) 0,01<P<0,001; (***) P<0,001",
    "ncbi_link": "SOX3: 20675
Sox3: 20675"
  },
  {
    "caption": " (A) SOX3 over-expression experiments in chicken spinal cord at E4. 48 hrs post electroporation, transfected side showed decreased expression of FGFR2, NFIA and Fgfr3. Bar: 50µm. (B) 24 hrs after miss-expression of a dominant negative version of SOXB1 (dnSOXB1), premature expression of FGFR2, NFIA and Fgfr3 were found in the transfected side. Bar: 40µm. (C) 24 hrs after SOX9 over-expression in chicken spinal cord (at E4), increased expression of FGFR2, NFIA and Fgfr3 was shown compared to the un-transfected control side. Bar: 40µm. (D) Sox3 and Sox9 co-electroporation in chicken spinal cord at E4 could rescue the effect of SOX9 overexpression and FGFR2, NFIA and Fgfr3 levels were comparable to the un-transfected control side. Embryos were analyzed 24 hrs post electroporation. Bar: 40µm. (E ",
    "ncbi_link": "FGFR2: 396259
Fgfr3: 396515
NFIA: 396210
SOX3: 20675
Sox3: 374019
SOXB1: 374019///396105///374240
SOX9: 374148
Sox9: 374148"
  },
  {
    "caption": "(C) Quantification of AQR position in adult WT, cst-1 and/or cst-2 mutant animals. The full length between the URXs and the end of the nematode tail is divided into 10 blocks, and the percent of AQR that stopped within each block is indicated. ***, P < 0.001 by Fisher's exact test. N = 50 - 109.",
    "ncbi_link": "cst-1: 180708
cst-2: 180707"
  },
  {
    "caption": "(E - F) Fluorescence time-lapse images of F-actin, plasma membrane and histone during AQR/QR.ap migration in WT (E) or cst-1; cst-2 double mutant (F) animals. Merged images, left; inverted fluorescence images of F-actin, right; white arrows, migration direction; asterisks, nucleus; double headed arrows, migration distance. F-actin is labeled with GFP-tagged with the actin-binding domain of Moesin (GFP::Moesin ABD), and the plasma membrane and Histone are labeled with mCherry-tagged with a myristoylation signal and a histone. The dotted lines indicate the cell periphery. Time is presented in minutes. Scale bars, 5 μm. (G - J) Quantification of the QR.ap migration angle (G & H), distance (I) and speed (J). Each line in (G & I) represents the measurement from one time-lapse movie. Error bars indicate SD. N = 10 - 17. Statistical significance is based on Student's t-tests, **, P < 0.01; ***, P < 0.001.",
    "ncbi_link": "cst-1: 180708
cst-2: 180707"
  },
  {
    "caption": "(A) Fluorescence time-lapse images of F-actin, plasma membrane and histone during QR.ap migration in mig-2(rh17) gain-of-function mutant animals. Merged images, left; inverted fluorescence images of F-actin, right; white arrows, migration direction; asterisks, nucleus; double headed arrow, migration distance. The dotted lines indicate the cell periphery. Time is presented in minutes. Scale bar, 5 μm. (B - C) Quantification of the QR.ap migration angle (B) and distance (C). N = 10.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(E) In vitro phosphorylation assay of CST-1/2 to MIG-2. Bacterially expressed His-tagged MIG-2 or His-tagged MIG-2S139A were incubated with the GST-tagged kinase domain of GST-CST-1/2 (1-318 aa). The kinase may use ATP-γ-S as a phosphodonor to thiophosphorylate its substrate; thus, the phosphorylation reaction was performed with ATP-γ-S, and anti-thiophosphate ester antibody was used to detect substrate phosphorylation (Allen et al, 2005; Allen et al, 2007). The final reaction was probed via immunoblotting with antibodies as indicated. Thio, thiophosphate ester.",
    "ncbi_link": "MIG-2: 181344"
  },
  {
    "caption": "(A) Quantification of AQR position in mig-2(mu28) null mutant animals with different rescue transgenes. N = 108 - 114. *, P < 0.05; ##, P < 0.01, phenotype enhanced. P values are based on Fisher's exact tests.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(B) Quantification of AQR position in WT and knock-in animals that harbor mig-2S139 point mutations. N = 100 - 111. ***, P < 0.001 by Fisher's exact test.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(C - F) Quantification of the QR.ap migration angle (C & D), distance (E) and speed (F) in mig-2S139A/E mutant animals. Each line in (C & E) represents the measurement from one movie of QR.ap migration. Error bars indicate SD. N = 12 -17. **, P < 0.01; ***, P < 0.001 by Student's t tests.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(G) Inverted fluorescence images (up) and schematics (down) of QR.ap in WT, cst-1; cst-2 double or mig-2 mutant animals. The plasma membrane and histones were labeled with mCherry. Scale bar, 5 μm. (H) Area ratio between the cell body and the nucleus in WT and mutant animals. Error bars indicate SD. N = 17 - 22. *, P < 0.05; **, P < 0.01; ***, P < 0.001 by Student's t tests.",
    "ncbi_link": "cst-1: 180708
cst-2: 180707
mig-2: 181344"
  },
  {
    "caption": "(I - K) Representative frames (upper) and quantification (lower) of F-actin enrichment at the QR.ap periphery in WT (I) and mig-2S139A/E mutant animals (J & K). The trace starts from the rear of the QR.ap and moves along the cell periphery to the leading edge (L) and back to the rear (R). F-actin was labeled with GFP::Moesin ABD; the plasma membrane and histone were marked with mCherry fluorescence. Green lines, F-actin fluorescence intensity; red lines, plasma membrane fluorescence intensity; dotted lines, cell periphery. Double-headed arrows indicate the F-actin enrichment region, in which the fluorescence intensity is 2-fold higher than the background. Scale bars, 5 μm. (L) Quantification of F-actin enrichment ratio in WT and mig-2 mutants. Error bars indicate SD. N = 28 - 68. **, P < 0.01; ***, P < 0.001 by Student's t-tests.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(A - C) Fluorescence images (upper) and quantifications (lower) of GFP-tagged CST-1 (A & B) or GFP-labeled F-actin (C) and mCherry tagged plasma membrane and histone in WT and mig-2 null mutant animals. The membrane protrusions in the white boxes are enlarged 3 times at the bottom. Yellow dashed lines indicate the cell periphery. White lines indicate the line to measure the fluorescence intensity. Green lines denote the CST-1 fluorescence intensity; red lines denote the plasma membrane fluorescence intensity; double-headed arrows denote the distance between the GFP signal and cell periphery. Scale bars, 5 μm. (D) Distance between GFP::CST-1 or GFP::Moesin ABD and the plasma membrane at the leading edge in WT and mig-2 null mutants. Error bars indicate SD. N = 9 - 14. ***, P < 0.001 by Student's t test.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "(E - F) Fluorescence images (left) and quantifications (right) of GFP-tagged CST-1 and mCherry tagged plasma membrane and histone in WT and mig-2 null mutant animals. Blue lines, sites of measurements; dotted lines, cell periphery; Green lines; CST-1 fluorescence intensity; red lines, mCherry fluorescence intensity. Scale bars, 5 μm. (G) Quantification of the fluorescence intensity ratio of GFP::CST-1 and mCherry-membrane between the leading edge and the lagging edge of AQR in WT and mig-2 null mutant animals. Error bars indicate SD. N = 20. ***, P < 0.001 by Student's t test.",
    "ncbi_link": "mig-2: 181344"
  },
  {
    "caption": "B. Srs2 requirement in de novo telomere addition in cells with and without functional HR. All strains are pif1-m2. Strains used: NK1264; NK2375, NK2376; NK2014, NK2015; NK2451, NK2452; NK2012, NK2013; NK2457, NK2458; NK2363, NK2364; NK2469; 2369, NK2370; NK2473-2475.",
    "ncbi_link": "pif1: 854941
Srs2: 853353"
  },
  {
    "caption": "D. Dynamics of (TG1-3)n addition monitored by qPCR through a time-course experiment (asynchronous populations). The Y axis shows a fold increase in de novo telomere-specific PCR product relative to the background levels at 0 h and normalised against an internal control (ARO1 locus). Average ± SD (n=3) is shown for each time-point of each genotype. Strains used: NK3292, NK3293; NK4670, NK4671; NK4112, NK4113; NK4114, NK4115; NK3292 est2∆, NK3293 est2∆; NK4232, NK4233.",
    "ncbi_link": "ARO1: "
  },
  {
    "caption": "F. Comparative analysis of ssDNA/dsDNA at de novo telomere addition loci in SRS2 and srs2Δ during a time-course experiment (synchronised populations). The Y axis shows a fold increase in de novo telomere-specific PCR product relative to the background levels at 0 h and normalised against an internal control (ARO1 locus). Average ± SD (n=3) is shown for each time-point of each genotype. Top set of error bars represents SD in relative increase of the de novo telomere-specific PCR product (as in panel D) while the lower set of error bars corresponds to quantifications of ss/dsDNA fractions. Strains used: NK3292, NK3293; NK4670, NK4671.",
    "ncbi_link": "ARO1: 
srs2: 853353"
  },
  {
    "caption": "B. Southern blot analysis of re-synthesis of resected DNA during BIR in SRS2 and srs2Δ corresponding to the data quantifications in C. DNA was digested with EcoRI and BamHI, resolved on 0.7% agarose gels, transferred onto charged Nylon membrane and hybridised to the mixture of 4 probes (three RS probes and a reference probe, REF, hybridizing to an ARS522-containing fragment on chr. V which is not involved in the repair). A representative image of one of the three repeats is shown.C. Re-synthesis of resected DNA on chr.VIIL in SRS2 and srs2Δ cells (solid and dashed lines, respectively) at the distance of 15.2 (RS15.2), 6.8 (RS6.8) and 2.6 (RS2.6) kb away from the homology region. Average ± SD (n=3) is shown for each time point.",
    "ncbi_link": "srs2: 853353"
  },
  {
    "caption": "D. Southern blot analysis of BIR-dependent DNA synthesis in SRS2 and srs2Δ corresponding to the data quantifications in D. DNA was digested with EcoRI and BamHI, resolved on 0.7% agarose gels, transferred onto charged Nylon membrane and hybridised to the mixture of 4 probes (three BIR probes and a reference probe, REF, hybridizing to an ARS522-containing fragment on chr. V which is not involved in the repair). A representative image of one of the three repeats is shown. C - control strain NK3980.E. BIR-dependent DNA synthesis in SRS2 and srs2Δ cells (solid and dashed lines, respectively) at the distance of 6 (BIR6), 36 (BIR36) and 77 (BIR77) kb away from the homology region. Average ± SD (n=3) is shown for each time point.",
    "ncbi_link": "srs2: 853353"
  },
  {
    "caption": "B. Frequency of DSB repair via SSA in SRS2 and srs2Δ cells with and without functional HR in the assay based on the system shown in panel A. Average ± SD (n=4) is shown for each genotype. Strains used in B and D: NK4691-4693; NK4805-4808; NK5081-5084; NK5085-5091.",
    "ncbi_link": "srs2: 853353"
  },
  {
    "caption": "D. Fragment L formation in SRS2 and srs2Δ cells in the presence and absence of Rad51. Also see Figure EV3 for blot images. Average ± SD (n=4) is shown for each time point.",
    "ncbi_link": "Rad51: 856831
SRS2: 853353
srs2: 853353"
  },
  {
    "caption": "I, The log-rank (Mantel-Cox) test of overall survival of 239 Chinese lung cancer patients based on rs1663689 genotype.",
    "ncbi_link": "rs1663689: "
  },
  {
    "caption": "F, The location diagram shows 4C enrichment around the negative control and ADGRG6 probe. Representative images of nuclei stained with DNA FISH probes for SNP rs1666389 (green) and negative control (red) or ADGRG6 (red) in H460 and A549 cells. The numerical points in the figure show the percentage of colocation in seven slides (with a total of 80 nuclei). Arrows point to the colocation signals. Nuclei with green or red positive signal are listed in the counting range. Values shown are means ± SD. Scale bars, 5 μm. ns, nonsignificant, *p < 0.05, **p < 0.01, unpaired two-tailed Student's t test.",
    "ncbi_link": "rs1666389: 
ADGRG6: 57211"
  },
  {
    "caption": "H, eQTL analysis demonstrating the correlation between the rs1663689 genotype and the expression of ADGRG6 in the clinical patient cohorts. The p value of the linear model was assessed by the Kruskal-Wallis test. Values shown are means ± SD.",
    "ncbi_link": "rs1663689: 
ADGRG6: 57211"
  },
  {
    "caption": "A, Protein expression of ADGRG6 or Actin after ADGRG6 knockdown in T/T cells and overexpression in C/C cells.",
    "ncbi_link": "ADGRG6: 57211"
  },
  {
    "caption": "Boyden chamber assay (C) of ADGRG6-knockdown T/T cells and ADGRG6-overexpressing C/C cells. Values shown are means ± SD obtained from one experiment. Scale bars, 200 μm. Three independent experiments were performed. **p < 0.01, ****p < 0.0001, unpaired two-tailed Student's t test.",
    "ncbi_link": "ADGRG6: 57211"
  },
  {
    "caption": "B, C Histograms of normalized  allele counts  in individuals 75+ years old compared to all age groups (N=125,748) across (B) all chromosome 19 SNPs  and small insertions/deletions, and (C) missense SNPs  and indels only. Dotted vertical lines show centSIRT6.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "C Quantitative mass spec of histone H3  peptide purified from human  cells expressing different SIRT6   alleles did not reveal a difference in acetylation  levels. Relative fraction represents the portion of the peptide encompassing  H3K9-17 compared to the summed total of all of the peptide quantitation values for the same region. n=3 biological replicates (BR); error bars=SD. Students t-test, two tailed",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "D Whole cell  histone H3 acetylation  levels in cumate-inducible SIRT6 human fibroblasts, assessed by Western blot. Cu, cumate; PQ, paraquat. Cumate  dosage required for equivalent SIRT6   protein abundance was determined by Western blot, and administered accordingly to respective cell lines Cells were incubated with appropriate cumate  dose for 48hrs prior to harvest, with PQ-treated cells receiving PQ  24hrs after initial cumate  induction.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "E-H Relative abundance of H3K9ac at SIRT6-dependent  NF-κB target genes. Anti-H3K9ac  antibodies were used to perform ChIP  in the absence (-Cu) or presence of (+Cu) cumate-induced SIRT6  expression. Samples were normalized using 10% input. n=3 BR; error bars=SD. Students t-test, two tailed. Black asterisk indicate p<0.05 compared to -Cu condition. Red asterisk indicated p<0.05 compared to +Cu  WT.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "I, J Relative abundance of H3K18ac at  satellite repeats associated with SIRT6   deacetylase activity. Anti-H3K18ac  antibodies were used to perform ChIP  in the absence (-Cu) or presence of (+Cu) cumate-induced SIRT6   expression. Samples were normalized using 10% input. n=3 TR; error bars=SD. Students t-test, two tailed. Black asterisk indicate p<0.05 compared to -Cu  condition.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "A  qRT-PCR  analysis of LINE1  expression in cumate-inducible SIRT6 fibroblasts. Primers assessed both 5' (ORF1) and 3' (ORF2) LINE1  sequences from the L1HS family of evolutionarily active LINE1  retrotransposons. Assessment of both regions was conducted to mitigate contributions from partial insertion sequences in coding genes. Asterisk indicate p<0.05. n=3 TR; error bars=SD. Students t-test, two tailed.",
    "ncbi_link": "LINE1: 
SIRT6: 51548"
  },
  {
    "caption": "B LINE1 EGFP retrotransposition assay. Three independent transfections with LINE1 EGFP  reporter plasmid were conducted and quantified by flow cytometry. Asterisk indicate p<0.05. Red asterisk indicated significance over SIRT6  KO control. Black asterisk indicate significance over WT SIRT6. n=3 BR; error bars=SD. Two-way ANOVA.",
    "ncbi_link": "EGFP: 
LINE1: 
SIRT6: 51548"
  },
  {
    "caption": "D, E Stimulation of NHEJ  and HR  by SIRT6  variants. Reporter cell lines were co-transfected with SIRT6-expressing plasmid, I-Sce1 plasmid, and DsRed  transfection control. After 72 hr recovery, reactivation of the GFP  reporter was measured by  flow cytometry. Stimulation of NHEJ  or HR  was calculated as radio of GFP+/DsRed+ positive cells. Blots  demonstrate equivalent SIRT6  abundance in transfected cells. Asterisk indicate p<0.05 Black asterisk indicate significance over control, red asterisk indicate significance over WT SIRT6. n=3 BR; error bars=SD. Two-way ANOVA",
    "ncbi_link": "DsRed: 
I-Sce1: 854590
SIRT6: 51548"
  },
  {
    "caption": "F Basal γH2AX foci in cumate-inducible SIRT6 fibroblasts. Foci were scored in at least 80 cells per condition. Asterisk indicate p<0.05. n=3 BR; error bars=SD. Students t-test, two tailed.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "G DNA repair kinetics in cumate-inducible SIRT6 fibroblasts. Cells were grown on slides and irradiated with 2 Gy gamma radiation, followed by immunostaining  for γH2AX. Irradiation  was conducted when the cells were at 75% confluency on slides. Cells were fixed and foci scored at t=0.5 hr, 2 hr, 4 hr, 6 hr, and 24 hr post-irradiation. Foci were scored in at least 80 cells per genotype per time point. Asterisk indicate p<0.05. Asterisks indicate significance over WT SIRT6. Color of the asterisk corresponds to the SIRT6   allele. n=3 BR; error bars=SD. Students t-test, two tailed.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "H, I Oxidative stress resistance. Cumate-inducible SIRT6 fibroblasts  were induced for SIRT6   expression and exposed to paraquat for 24 hours. Resistance was determined by apoptosis staining  48 hours after exposure. Asterisk indicate p<0.05. Asterisks indicate significance over WT SIRT6. Color of the asterisk corresponds to the SIRT6   allele. n=3 BR; error bars=SD. Students t-test, two tailed.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "A Number of adherent cells after transfection with SIRT6  variants. Cells were transfected with SIRT6  plasmids encoding different SIRT6  alleles and cell numbers were counted after 72 hours. HCA2  are normal human foreskin fibroblasts. Asterisk indicate p<0.05. n=3 BR; error bars=SD. Students t-test, two tailed.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "B, C Apoptosis staining  of cancer cell lines 48 hours after transfection. Cells were stained  with Annexin V/PI  and analyzed by flow cytometry. Asterisk indicate p<0.05. Red asterisk indicates significance over control, black asterisk indicates significance over WT SIRT6. n=3 BR; error bars=SD. Two-way ANOVA.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "B IP  experiments on lysates from cumate-induced fibroblasts  expressing wild type or centSIRT6 alleles with antibodies to SIRT6, LMNA, and mADPr. SIRT6   expression was induced 48 hours prior to IP. n=3 BR. One representative set of IPs  is shown.",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "C CentSIRT6 shows stronger interaction with LMNA  compared to the wild type SIRT6. Quantification of the IP  experiment shown in (B). SIRT6 IP  followed by  Western blot  with antibodies to LMNA. D LMNA  shows enhanced interaction  with centSIRT6 compared to the wild type. Quantification of the IP  experiment shown in (B). LMNA IP  from cumate-inducible SIRT6 fibroblasts  followed by Western blot  with antibodies to SIRT6. Data information: n=3 BR; error bars=SD. Students t-test, two tailed. Asterisk indicate p<0.05",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "E centSIRT6  shows enhanced mADPr. Quantification of the IP experiment shown in (B). SIRT6 IP  from cumate-inducible SIRT6 fibroblasts  followed by Western blot with antibody to mADPr  residues F LMNA  shows enhanced mADPr  signal in cells expressing centSIRT6. Quantification of the IP  experiment shown in (B). IP  with mADPr  antibody using extract from cumate-induced SIRT6 fibroblasts, followed by Western blot  with antibodies to LMNA. Data information: n=3 BR; error bars=SD. Students t-test, two tailed. Asterisk indicate p<0.05",
    "ncbi_link": "SIRT6: 51548"
  },
  {
    "caption": "Down regulation of SREBP target genes in Cideb-deficient liver. Microarray heatmap of fatty acids/cholesterol synthesis genes that were down-regulated in Cideb-/- mice and Scap liver-specific knockout mice, comparing to the respective WT controls (WT VS Cideb-/-, WT VS L-Scap-/-, n = 2 per group). The expression level of each gene was linearly normalized to range from -1 to 1 before plotting.",
    "ncbi_link": "Cideb: 12684
Scap: 235623
SREBP: 235623"
  },
  {
    "caption": "Decreased SREBP processing and maturation in Cideb deficient liver. Immune blotting (IB) of the full length, precursor SREBP-1/2 (SREBP FL) and the cleaved, active SREBP-1/2 (SREBP N) from WT and Cideb-/- mice liver under ad-lib (ND), fasting 12h (F), and refeeding (R) conditions. Mice were refed with high-carbohydrate low-fat diet for 12h after 12h fasting.",
    "ncbi_link": "Cideb: 12684
SREBP: 235623"
  },
  {
    "caption": "Defective SREBP transcriptional response to refeeding in Cideb-deficient liver. Transcript levels of lipogenic and cholesterol metabolism genes determined by qPCR from WT and Cideb-/- liver under ad-lib (ND), fasting 12h (F), and refeeding (R) conditions. Mice were refed with high-carbohydrate low-fat diet for 12h after 12h fasting (n = 3 per group).",
    "ncbi_link": "Cideb: 12684
SREBP: 235623"
  },
  {
    "caption": "Re-introduction of Cideb rescues SREBP processing in Cideb-/- liver. WT and Cideb-/- mice were injected with AAV-GFP or AAV-Cideb, and sacrificed for IB with the indicated antibodies 20 days after the injection.",
    "ncbi_link": "GFP: 
Cideb: 12684
SREBP: 235623"
  },
  {
    "caption": "Re-introduction of Cideb rescues the expression of SREBP target genes in Cideb-/- liver. Transcript levels of lipogenic genes determined by qPCR from WT and Cideb-/- liver. WT and Cideb-/- mice were injected with AAV-GFP or AAV-Cideb, and sacrificed for qPCR 20 days after the injection (n = 3 per group).",
    "ncbi_link": "GFP: 
Cideb: 12684
SREBP: 235623"
  },
  {
    "caption": "Liver morphology of WT and Cideb-/- liver under chow diet and HFLF diet. H/E staining, oil red-O staining, immunohistochemistry and ultra-structure (Electron Microscope) were performed. Scale bar represented 50 µm in the upper three rows of images, and 2 µm in the bottom row of images. LD: lipid droplet, ER: endoplasmic reticulum, M: mitochondrial, N: nucleus.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Total liver TAG levels (B) of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Liver cholesterol ester levels (C) of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "D Loss of Cideb inhibits diet-induced SREBP activation. IB of hepatic SREBP processing and lipogenic enzyme levels (Fasn, Scd1) of WT and Cideb-/- mice under chow diet and HFLF diet.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "E Serum AST and ALT levels of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "F Cideb deficiency alleviates the whole body inflammation response. Serum TNFα, MCP1 and IL6 levels of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Serum fed glucose levels (G) of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Serum fed insulin levels (H) of WT and Cideb-/- mice under chow diet and HFLF diet (n = 8 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "I Glucose tolerance test (GTT) of WT and Cideb-/- mice under HFLF diet (n = 5 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "J Insulin tolerance test (ITT) of WT and Cideb-/- mice under HFLF diet (n = 5 per group). Data information: Data represent Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Decreased SREBP-1/2 and SCAP levels in Golgi apparatus in Cideb-/- mice. IB of organelle fractions of the indicated proteins and quantification of IB data from 3 independent experiments. Data information: Data represent the Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Cideb deficiency impairs the packaging of SCAP/SREBP into COPII vesicles. Protein present in the vesicle or microsome fractions obtained from WT or Cideb-/- liver were detected by IB. Quantification of IB data from 3 independent experiments. Data information: Data represent the Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Cideb depletion decreases the recruitment of SCAP to the COPII machinery in cells. Primary hepatocytes transfected with control or Cideb siRNA were infected with adenovirus expressing Sar1A-Flag-BirA*. Cells were cultured in sterol-depleted medium and treated with 80 µM biotin, prior to pulldown with streptavidin-conjugated beads. The biotinylated proteins were detected by IB with the indicated antibodies following SDS-PAGE.",
    "ncbi_link": "Flag: 
BirA: 948469
Cideb: 12684
Sar1A: 66397///20224"
  },
  {
    "caption": "Cleaved SREBP bypasses Cideb deficiency. WT and Cideb-/- mice were injected with adenovirus expressing GFP, SREBP-1c full length (FL) or SREBP-1c active form (N). Mice were sacrificed 7 days after injection, and liver TAG levels and hepatic expression SREBP-1 target genes in the indicated groups were determined (n=5 per group). Data information: Data represent the Mean ± SEM; NS: not significant, *: p < 0.05, **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "GFP: 
SREBP: 
SREBP-1: 
SREBP-1c: 
Cideb: 12684"
  },
  {
    "caption": "Cideb co-precipitates with SCAP. Flag-tagged Cideb was co-expressed with different HA-tagged proteins (PLIN2, Insig, SCAP, SREBP-1 or SREBP-2) in 293T cells and immuno-precipitated with an anti-Flag antibody, and the co-immunoprecipitated protein were detected by an anti-HA antibody following SDS-PAGE.",
    "ncbi_link": "Cideb: 
Flag: 
HA: 
Insig: 
PLIN2: 
SCAP: 
SREBP-1: 
SREBP-2: "
  },
  {
    "caption": "Cideb interacts with the 416-800 portion of SCAP. Flag-tagged Cideb was co-expressed with the indicated HA-tagged SCAP truncation mutants in 293T cells and immuno-precipitated with an anti-Flag antibody. Levels of the co-immunoprecipitated protein were detected by an anti-HA antibody following SDS-PAGE.",
    "ncbi_link": "Cideb: 
SCAP: "
  },
  {
    "caption": "Sterol-dependent interaction switch of SCAP. SCAP interacts with Insig in the presence of sterol, while switches to Cideb binding upon sterol deprivation. Flag-tagged Insig-1 or Cideb was co-expressed with HA-tagged SREBP-2 and SCAP or SCAP-Y298C in CHO-K1 cells in sterol-depleted medium. When indicated, 10 µg/ml 25-HC were supplemented before cells were immuno-precipitated with an anti-Flag antibody, and the levels of co-immunoprecipitated proteins were detected by IB following SDS-PAGE. The dotted blue vertical line was drawn to separate the result between SCAP-WT and SCAP-Y298C.",
    "ncbi_link": "Cideb: 
Flag: 
HA: 
Insig-1: 
SCAP: 
SREBP-2: "
  },
  {
    "caption": "Cideb relieves sterol-dependent suppression of SREBP processing. Hepatocytes infected with adenovirus expressing GFP or Flag-Cideb were cultured in sterol deprived condition. When indicated, cells were treated with different doses of 25-HC before subjected to IB with the indicated antibodies following SDS-PAGE. Quantification of IB data from 3 independent experiments. Data represents Mean ± SEM.",
    "ncbi_link": "Cideb: 
Flag: 
GFP: "
  },
  {
    "caption": "Cideb promotes Golgi localization of SCAP. HepG2 cells transfected with GFP-SCAP alone or with HA-Cideb were cultured in sterol deprived conditions or treated with 1 µg/ml 25-HC. Cells were fixed and subjected to confocal microscopy following staining with antibodies against GM130 or HA. Scale bars represent 10 µm (Merge), and 2 µm (Inlay). Bottom: quantification of the percentage of SCAP localized in Golgi-positive region per cell (left) and quantification of the percentage of cells containing Golgi-localized GFP-SCAP (right) under indicated conditions, from 3 independent experiments; Data represent Mean ± SEM; **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Cideb: 
GFP: 
HA: 
SCAP: "
  },
  {
    "caption": "Cideb interacts with Sec12. 293T cells transfected with Cideb and GFP-tagged Sec12, Sec23, Sec16S, or Sec16L were subjected to immuno-precipitation with an anti-Cideb antibody, and levels of the co-immunoprecipitated protein were detected by an anti-GFP antibody.",
    "ncbi_link": "Cideb: 
GFP: 
Sec12: 
Sec23: 
Sec16L: 9919
Sec16S: 89866"
  },
  {
    "caption": "Co-localization of SCAP and Cideb at the ER exit sites. HepG2 cells transfected with GFP-SCAP and HA-Cideb were arrested with 10 µM BFA and 1 µM Nocodazole for 2 hours, then fixed with methanol and stained with antibodies against Sec12 or HA. 3D reconstruction was obtained by processing 3D-original image with Imaris. Scale bars represent 10 µm (Merge), and 1 µm (Inlay and 3D reconstruction).",
    "ncbi_link": "Cideb: 
GFP: 
HA: 
SCAP: "
  },
  {
    "caption": "Localization of Cideb at the ER exit sites. AML12 cells knocked-in with a GFP tag at the C-terminus of Cideb genome was treated with 10 µM BFA for 1 hour, then fixed with methanol and stained with antibodies against Sec12. Scale bars represent 10 µm (Merge), and 1 µm (Inlay).",
    "ncbi_link": "Cideb: 
GFP: "
  },
  {
    "caption": "Sec12 interacts with the 118-165 portion of Cideb. HA-tagged Sec12 was co-expressed with the indicated Flag-tagged Cideb truncation mutants in 293T cells and immuno-precipitated with an anti-Flag antibody. Levels of the co-immunoprecipitated protein were detected by an anti-HA antibody following SDS-PAGE.",
    "ncbi_link": "Cideb: 
Flag: 
HA: 
Sec12: "
  },
  {
    "caption": "Lysine 128 of Cideb is required for the interaction with Sec12. 293T cells transfected with HA-Sec12 and the indicated Flag-tagged Cideb constructs were subjected to immunoprecipitation with an anti-Flag antibody, and levels of the co-immunoprecipitated HA-Sec12 were detected with an anti-HA antibody.",
    "ncbi_link": "Cideb: 
Flag: 
HA: 
Sec12: "
  },
  {
    "caption": "Recombinant Cideb interacts with Sec12. GST-Sec12 and MBP-tagged Cideb or Cideb-K128A were purified from E.coli and subjected to in vitro binding.",
    "ncbi_link": "Cideb: 
GST: 
MBP: 
Sec12: 
Cideb: 12684"
  },
  {
    "caption": "Cideb-K128A fails to promote SREBP processing. Cideb-/- mice were injected with adenovirus expressing GFP, Flag-Cideb, or Flag-Cideb-K128A, and sacrificed 7 days after injection. Liver lysates were subjected to IB with the indicated antibodies following SDS-PAGE and quantification of IB data from 3 independent experiments. Data represent Mean ± SEM; **: p < 0.01, ***: p < 0.001, by 2-tailed Student's t test.",
    "ncbi_link": "Flag: 
GFP: 
Cideb: 12684"
  },
  {
    "caption": "Cideb, but not Cideb-K128A, promotes SCAP/SREBP incorporation into COPII vesicles. Liver microsomes were isolated from mice expressing the indicated proteins and subjected to in vitro budding assay. Resulting vesicles and the donor microsomes were subject to IB with the indicated antibodies following SDS-PAGE.",
    "ncbi_link": "Cideb: 12684"
  },
  {
    "caption": "Cideb enriches SCAP to ERESs via interacting with Sec12. CHO-K1 cells transfected with GFP-SCAP, HA-Cideb or HA-Cideb-K128A were arrested with 5 µM Nocodazole for 30 min, then fixed with methanol and stained with antibodies against Sec12 and HA. Scale bars represent 10 µm (left), and 2.5 µm (Inlay).",
    "ncbi_link": "Cideb: 
GFP: 
HA: 
SCAP: "
  },
  {
    "caption": " Figure 1b. Genotyping of AS and WT CDK12 clones. Ethidium bromide-stained agarose gel visualizing PCR products from genomic DNA of AS (AS-PCR) and WT (WT-PCR) CDK12 HCT116 cells and their digest with BslI enzyme (indicated as AS- BslI and WT- BslI). Primer positions and BslI restriction sites are depicted at Expanded View Fig. 1a. Numbers on the left and right indicate DNA marker and DNA fragment sizes, respectively. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": " Figure 1d. Effect of CDK12 inhibition on phosphorylation of the CTD of RNAPII. Western blot analyses of protein levels by the indicated antibodies in AS CDK12 HCT116 cells treated with 5 µM 3-MB-PP1 for indicated times. Long and short exp.= long (4-14 min) and short (10-60 s) exposures, respectively. FUS and tubulin are loading controls. A representative image from 3 replicates is shown. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": " Figure 1e, f. Inhibition of CDK12 in AS CDK12 HCT116 cells results in down-regulation of CDK12-dependent HR genes. Graph shows RT-qPCR analysis of relative levels of mRNAs of described genes in AS CDK12 HCT116 (e) and WT CDK12 HCT116 (f) cells treated for indicated times with 3-MB-PP1. mRNA levels were normalized to HPRT1 mRNA expression and the mRNA levels of untreated control (CTRL) cells were set to 1. n=3 replicates, error bars indicate standard error of the mean (SEM). ",
    "ncbi_link": "CDK12: 51755
HPRT1: 3251"
  },
  {
    "caption": " Figure 3d. Validation of RNA-seq for select DNA replication genes by RT-qPCR. Graph shows relative levels of mRNAs of described genes in serum arrested and released (0 h G0/G1) AS CDK12 HCT116 cells either treated (3-MB-PP1) or not (CTRL) with the inhibitor for indicated times after the release. mRNA levels were normalized to B2M mRNA expression and mRNA levels for each gene at the time of release (0 h) was set as 1. n=3 replicates, error bars indicate SEM. ",
    "ncbi_link": "B2M: 567
CDK12: 51755"
  },
  {
    "caption": " Figure 3f. CDK12 inhibition affects loading of CDC6 and CDT1 DNA replication factors to chromatin. Western blotting analyses of chromatin association of the indicated DNA replication factors in serum synchronized and released AS CDK12 HCT116 cells treated or not with 3-MB-PP1 for the indicated times. Histone H2A serves as a loading control of chromatin fractions. A=asynchronous cells, 0 h=time of release. A representative Western blot of 3 replicates is shown. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": " Figure 4e. Rescued loading of CDC6 and CDT1 on chromatin after removal of CDK12 inhibitor. Western blot analyses of chromatin fractions of serum starved AS CDK12 HCT116 cells treated with 3-MB-PP1 for 6 or 9 h or with the inhibitor washed off after 1 h of treatment. CTRL corresponds to cells not treated with the inhibitor at the time of the serum addition. All cells were harvested either 6 or 9 h after the serum addition. Histone H2A serves as a loading control of chromatin fractions and studied DNA replication factors are indicated. A representative image of three replicates is shown. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": " Figure 4f. Inhibition of CDK12 kinase activity in cycling cells leads to decreased numbers of actively replicating cells. Asynchronous AS CDK12 HCT116 cells were grown for 24 and 48 h in the presence or absence of 3-MB-PP1 and replicating BrdU-stained cells were quantified by FACS analyses. CTRL=control samples without the 3-MB-PP1. A representative image of 3 replicates is shown. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": " Figure 5d Examples of genes whose transcription processivity and expression is dependent on the CDK12 kinase activity. Nuclear RNA-seq data on the respective strand and RNAPII, P-Ser2, P-Ser5 and SPT6 ChIP-seq data for MED13 genes from cells either treated (red) or not (blue, CTRL) with 3-MB-PP1 were visualized with Gviz. Read counts were normalized to the total number of mapped reads per sample and averaged between replicates. Blue and red boxes below the RNA-seq data indicate the 90% distance in control and CDK12 inhibited samples, respectively. ",
    "ncbi_link": "MED13: 9969"
  },
  {
    "caption": " Figure 5d e. Examples of genes whose transcription processivity and expression is dependent on the CDK12 kinase activity. Nuclear RNA-seq data on the respective strand and RNAPII, P-Ser2, P-Ser5 and SPT6 ChIP-seq data for UBE3C genes from cells either treated (red) or not (blue, CTRL) with 3-MB-PP1 were visualized with Gviz. Read counts were normalized to the total number of mapped reads per sample and averaged between replicates. Blue and red boxes below the RNA-seq data indicate the 90% distance (see Fig. 7d and 7e and corresponding text) in control and CDK12 inhibited samples, respectively. ",
    "ncbi_link": "UBE3C: 9690"
  },
  {
    "caption": " Figure 8b. Transcription elongation rate decreases in bodies of CDK12-dependent but not CDK12-independent genes after CDK12 inhibition. Graphs show relative levels of pre-mRNAs of described genes in AS CDK12 HCT116 cells either treated with 3-MB-PP1 or not (CTRL) for indicated times after DRB wash off. Pre-mRNA levels were normalized to the samples not treated with DRB (Unt) for which the value was set as 1. n=3 independent experiments, error bars correspond to SEM. Positions of primers (designed to span exon-intron junctions) and their distance from the transcription start site in kb are indicated in the gene structures shown above the graphs. Figure 8c. Proposed model. Schema shows groups of genes whose RNAPII processivity is particularly sensitive to CDK12 catalytic activity and cellular functions that are especially dependent on optimal expression of these genes. The situation in cells with normal and aberrant CDK12 kinase activity is depicted. CDK12 (green oval) phosphorylates (P) unknown substrate(s) (orange oval), possibly including the CTD (blue line), which results in optimal elongation and processivity (blue arrow) of RNAPII (blue oval) for CDK12-sensitive genes. Full length, functional mRNAs are synthesized (upper panel). Inhibition of CDK12 leads to hyperphosphorylation (capital P) of Ser2 (S2) in bodies of CDK12-sensitive genes which is associated with slower elongation and premature termination. Shorter, aberrant mRNAs are made (lower panel). mRNAs are depicted as black lines. ",
    "ncbi_link": "CDK12: 51755"
  },
  {
    "caption": "Vessel stability. IsolectinB4 (IsoB4, green) and collagen IV (red) in P4 wildtype (WT) and Vegfr2Y1212F /Y1212F retinas. Arrows; collagen IV-positive empty sleeves. A; artery. Scale bar, 50 µm.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "Immunoblot showing VEGFR2 phosphorylation on pY1212, pY949 and pY1173. A. Anti-VEGFR2 immunoprecipitates (IP) from lung lysates from wildtype (WT) and Vegfr2Y1212F /Y1212F FVB mice, tail-vein injected with PBS or VEGF for 1 minute. Each lane (A) represent one individual mouse.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "VEGFR2/GRB2 and VEGFR2/PI3Kp85 complexes in isolated (i)ECs. E. PLA for VEGFR2/GRB2 and VEGFR2/PI3Kp85 complexes (black puncta) in iECs from FVB wildtype (WT) and Vegfr2Y1212F/Y1212F lungs. Hoechst 33342 show nuclei (grey). Scale bar, 20 µm. F, G. Fold-increase over PBS-treated sample; each dot represents the mean of 6 fields. 2-way ANOVA p=0.0206 (F), p=0.0368 (G); Sidak's multiple comparison test, * p <0.05. n=3 experiments.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "phosphoERK1/2 and phosphoAkt immunostaining (green) of iECs from FVB wildtype (WT) and Vegfr2Y1212F/Y1212F lungs. Hoechst 33342 (blue) shows nuclei. Arrows indicate nuclear accumulation of phosphoERK1/2 and phosphoAkt, respectively. Scale bar, 20 µm.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "Nuclear accumulation expressed as fold-increase of nuclear phosphoAkt area in Vegfr2Y1212F/Y1212F over PBS-treated wildtype (WT) iECs, normalized to the number of nuclei. Each dot represents 1 field. Min, minutes of stimulation. Unpaired T test, *p < 0.05. n=3 experiments.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "Immunoblot for phosphoERK1/2, total ERK1/2, phosphoAkt and total Akt on lung lysates from wiltype (WT) and Vegfr2Y1212F /Y1212F FVB mice tail-vein injected with PBS or VEGFA followed by circulation for time points indicated. Each lane represents one individual mouse. Quantification of phosphoERK1/2 /total ERK1/2 expressed as Fold change to PBS. Min, minutes of stimulation. Error bars: SD; 2-way ANOVA p=0.0025; unpaired T test, *p < 0.05. n=3 experiments. Quantification of phosphoAkt/total Akt expressed as Fold change to PBS. Min, minutes of stimulation. Error bars: SD; 2-way ANOVA p=0.0003; unpaired T test, *p < 0.05. n=3 experiments.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "Immunoblot for Myc on lung lysates from wiltype (WT) and Vegfr2Y1212F /Y1212F FVB mice tail-vein injected with PBS or VEGFA followed by circulation for time points indicated. Each lane represents one individual mouse. Quantification of Myc/Actin expressed as Fold change to PBS. Min, minutes of stimulation. Error bars: SD; 2-way ANOVA p=0.0058; unpaired T test, *p < 0.05, ** p <0.01. n=3 experiments.",
    "ncbi_link": "Vegfr2: 16542"
  },
  {
    "caption": "Myc protein expression. C. Myc and Actin immunoblotting on lysates of lung isolated ECs from untreated wildtype (WT) and mutant (VEGFR2 Y1212F) C57Bl/6 and FVB mice. D. Quantification of Myc/Actin expressed as Arbitrary unit. Each lane (C) and each dot (D) represent one individual mouse. 2-way ANOVA p <0.0001; unpaired T test, ** p <0.01. n=5-7.",
    "ncbi_link": "VEGFR2: 16542"
  },
  {
    "caption": "Baseline transcriptional level of Myc from lung isolated ECs from untreated wildtype (WT) and mutant (VEGFR2 Y1212F) C57Bl/6 and FVB mice. Each dot represents one individual mouse. 2-way ANOVA p=0.0041; Sidak's multiple comparison test, * p <0.05. n=4-5.",
    "ncbi_link": "VEGFR2: 16542
Myc: 17869"
  },
  {
    "caption": "Rescue of angiogenic sprouting by Myc overexpression in E11.5 C57Bl/6 Vegfr2Y1212F /Y1212F explant tissue. Representative images of E11.5 explants from C57Bl/6 embryos taken from wildtype (WT) and Vegfr2Y1212F /Y1212F littermates with (MycOE/Cre +) and without (MycOE/Cre-) endothelial-specific overexpression of Myc. Endothelial cell marker (CD31) immunostaining highlights the vasculature in white. Embryonic tissue blacked out to highlight sprouting area.",
    "ncbi_link": "Cre: 2777477
Vegfr2: 16542
Myc: 17869"
  },
  {
    "caption": "Rescue of angiogenic sprouting by Myc overexpression in E11.5 C57Bl/6 Vegfr2Y1212F /Y1212F explant tissue. Quantification as fold-increase of vessel sprouting area compared to WT MycOE/Cre -. Scale bar, 250 µm. Error bars: SD; unpaired T test, ** p <0.01, **** p <0.0001. n=4-11 explants, one explant/embryo.",
    "ncbi_link": "Cre: 2777477
Vegfr2: 16542
Myc: 17869"
  },
  {
    "caption": "Rescue of Ec proliferation. Myc overexpression in E11.5 C57Bl/6 Vegfr2Y1212F /Y1212F explant tissue. ERG (red), EdU (green) and double-positive cells (yellow; arrows).",
    "ncbi_link": "Vegfr2: 16542
Myc: 17869"
  },
  {
    "caption": "GSEAs showing upregulation of genes belonging to the K-Ras, Angiogenesis and mTORC1 gene sets in (WT) compared to VEGFR2 Y1212F isolated ECs. K-Ras and Angiogenesis gene sets derived from C57Bl/6 iECs kept in basal condition; mTORC1 gene set derived from C57Bl/6 iECs treated with VEGFA for 3h. See Supplementary Table 2. Enrichment score (ES), normalized ES (NES) are shown. P-values <0.05 were regarded as significant. Heat maps displaying gene regulation in gene sets shown in A. The color in the heatmap shows the gene expression value, expressed as a z-score across animals. Red color represents relative higher expression and blue color represents relative lower expression value. The z-score is calculated by (x-x')/s where x is individual gene expression, x' is the mean of the gene expression across samples and s is standard deviation of the gene expression across samples.",
    "ncbi_link": "VEGFR2: 16542
K-Ras: 16653
mTORC1: 56717"
  },
  {
    "caption": "Myc-regulated gene expression downstream of VEGFR2 pY1212. Quantitative PCR analysis of a set of known Myc-regulated transcripts in C57Bl/6 (C, D) and FVB (E, F) adult lungs at basal (C, E) and at 1 hour after tail-vein administration of VEGFA (D, F). FASN, fatty acid synthase; Ldha and -b, Lactate dehydrogenase A and B; Acod1, Aconitate Decarboxylase 1; Ppat, Amidophosphoribosyltransferase; Pde4d, cAMP-specific 3',5'-cyclic phosphodiesterase 4D; Prkaca, cAMP-dependent protein kinase catalytic subunit alpha. Error bars: SD; 2-way ANOVA between WT and Vegfr2Y1212F /Y1212F p=0.0453 (C), p < 0.0001 (D), p=0.0018 (E), p=0.09 (F); unpaired T test, *p < 0.05, **p < 0.01, ***p < 0.001. C57Bl/6 n=8-11 mice, FVB n=9-14 mice.",
    "ncbi_link": "Myc: 
Acod1: 16365
Aconitate Decarboxylase 1: 16365
FASN: 14104
fatty acid synthase: 14104
Vegfr2: 16542
VEGFR2: 16542
Lactate dehydrogenase A: 16828
Ldha: 16828
cAMP-specific 3',5'-cyclic phosphodiesterase 4D: 238871
Pde4d: 238871
Amidophosphoribosyltransferase: 231327
Ppat: 231327
cAMP-dependent protein kinase catalytic subunit alpha: 18747
Prkaca: 18747"
  },
  {
    "caption": "GFP-tagged DIA1, DIA1(M1190D), and DIA1(R1204X) plasmids were transfected into MDCKmCherry-ESPIN1 cells cultured on membrane inserts. Twenty-four hours after transfection, a reconstructed lateral view of fixed cells was generated using a confocal laser fluorescence microscope. Arrows indicate the elongated microvilli visualized by mCherry-ESPIN1 with GFP-hDIA1(R1204X) expression. Scale bars: 5 μm. Representative of 3 experiments.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "Various GFP-tagged DIA1 plasmids were transfected into HeLa cells, and fixed 24 h after transfection. Fixed cells were stained with Alexa568-conjugated phalloidin and DAPI (A, B: representative of 5 experiments).(A) Stress fiber formation was observed with a confocal laser microscope. Note the induction of stress fibers by GFP-DIA1(M1190D) (asterisks). Arrow and arrowheads indicate a plasma membrane (PM) localization of GFP-DIA1(M1190D) and a dot-like localization of GFP-DIA1(R1204X) adjacent to the PM, respectively. Inset in the top panel of DIA1 (R1204X) shows the magnified image of the region indicated by rectangle. Scale bars: 10 μm..",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "Various GFP-tagged DIA1 plasmids were transfected into HeLa cells, and fixed 24 h after transfection. Fixed cells were stained with Alexa568-conjugated phalloidin and DAPI (A, B: representative of 5 experiments).(B) Microvilli with or without GFP-DIA1(R1204X) expression were observed under a confocal laser microscope. Note elongated and thick microvilli (arrowheads) in GFP-DIA1(R1204X)- transfected cells, but not in non-transfected cells (circles). 3D movies are available in Movie EV1 (R1204X), Movie EV2 (WT), and Movie EV3 (ttaa). Scale bar: 10 μm.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "GFP-tagged DIA1(WT), DIA1(R1204X), and DIA1(M1190D) were transfected into XTC cells. XTC cells were spread on the PLL-coated coverslips and time-lapse images were acquired every 300 ms, illuminating the restricted areas near the cell edges, by using a single-molecule speckle microscope. Representative images are shown for DIA1(WT) (A, Movie EV5), DIA1(R1204X) (B, Movie EV6), and DIA1(M1190D) (C, Movie EV7). Circles indicate speckles showing directional movement over a distance of several micrometers. Trajectories of these speckles are also illustrated, and crosses were plotted at the end of the directional movement. Speckles showing directional movement were frequently observed in cells expressing GFP-DIA1(R1204X) (B), whereas such speckles were scarce in cells expressing GFP-DIA1(WT) (A). However, the density of these speckles in GFP-DIA1(R1204X)-expressing cells appeared lower than that in GFP-DIA1(M1190D)-expressing cells, which is considered a fully active mutant (C). To evaluate the frequency of speckles indicating directional movement, we performed a quantitative analysis (D). The number of speckles showing directional movement during 3 continuous planes was counted and were normalized by the fluorescent intensity of each cell, which corresponds to the expression level of the GFP-tagged protein. *P= 0.0288 and **P= 0.0002 Bonferroni's post hoc test following one-way ANOVA (WT; n = 5, R1204X; n = 6, M1190D; n = 6). Time is in seconds. Scale bars: 5 µm.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "Cochleae from control, heterozygous Dia1-KO (Dia1-/+) and homozygous Dia1-KO (Dia1-/-) mice were fixed at 5 weeks of age (A, B; representative of n=6).(A) Paraffin-embedded 4 μm sections of cochlea were stained with hematoxylin and eosin. No hair cell (HC) loss (either IHC or OHC) is observed at the basal turn of the Dia1-/+ or Dia1-/-cochleae. No obvious differences are observed in the spiral ganglion (SV), spiral ligament (SL), stria vascularis (SV), and Reissner's membrane (RM) in Dia1-/+, or Dia1-/-mice compared with control mice. Lower panels (Scale bars: 20 µm) are magnified images of the region indicated rectangle in upper panels (Scale bars: 100 µm).",
    "ncbi_link": "Dia1: 13367"
  },
  {
    "caption": "Cochleae from control, heterozygous Dia1-KO (Dia1-/+) and homozygous Dia1-KO (Dia1-/-) mice were fixed at 5 weeks of age (A, B; representative of n=6).(B) Basal turns of the dissected cochleae were immunostained using a Myo7a Ab followed by an Alexa488 secondary Ab with DAPI as a nuclear counterstain. No HC loss (either IHC or OHC) is observed in Dia1-/-mice. Scale bars: 20 µm.",
    "ncbi_link": "Dia1: 13367"
  },
  {
    "caption": "(C) ABR thresholds (10, 20, 40 kHz) in control and Dia1-/-mice at 5 weeks of age (dB SPL, mean SE). No hearing loss was observed in Dia1-/-mice (n = 8) compared with control mice (n = 4).",
    "ncbi_link": "Dia1: 13367"
  },
  {
    "caption": "(A), Age-related click and pure tone-burst (8, 16, 24, 32 kHz) ABR thresholds (dB SPL, mean SE) in DIA1(R1204X)-TG (5 weeks, n = 6; 10 weeks, n = 16; 25 weeks, n = 42) and control mice (5 weeks, n = 6; 10 weeks, n = 16; 25 weeks, n = 33). Note the progressive hearing loss of DIA1(R1204X)-TG mice starting at high frequency sounds from 10 weeks. **P= 0.0039 (24 kHz) and **P< 0.0001 (32 kHz) at 10 weeks and **P< 0.0001 (click), **P< 0.0001 (8 kHz), **P= 0.0001 (16 kHz), **P< 0.0001 (24 kHz), and **P< 0.0001 (32 kHz) at 25 weeks by Bonferroni's post hoc test following two-way ANOVA.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "(B) Representative SEM images of the organ of Corti at the basal turn obtained from DIA1(R1204X)-TG and control mice at 5, 10, and 25 weeks of age. White and red circles show IHC and OHC losses, respectively. Note OHC-dominant HC loss. Scale bars: 5 µm.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "(C) The percentages of remaining OHC and IHC in each turn in DIA1(R1204X)-TG and control mice at 25 weeks of age (n = 5). Schematic illustration shows the regions of the cochlea divided into three parts: Ap; apical turn, Md; middle turn, Bs; basal turn. **P= 0.0017 (OHC at Md), **P< 0.0001 (OHC at Bs), *P= 0.0117 (IHC at Ap), *P= 0.0330 (IHC at Md), and **P= 0.0003 (IHC at Bs) by Bonferroni's post hoc test following two-way ANOVA.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "(D) DPOAE (f2 frequency at 8, 12, 16, 20 kHz) amplitude (dB SPL, mean SE) in DIA1(R1204X)-TG (n = 37) and control mice (n = 30) at 25 weeks of age. *P= 0.0127, **P= 0.0029 (at 12 kHz), and **P= 0.0013 (at 16 kHz) by Bonferroni's post hoc test following two-way ANOVA.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "(E) High magnification SEM images of OHCs and IHCs at the basal turn of cochlea obtained from DIA1(R1204X)-TG and control mice at 25 weeks of age. Note the sparse and short (arrow) stereocilia of OHC, and sparse and fused (arrowheads) stereocilia of IHC in DIA1(R1204X)-TG mice. Scale bars: 1 µm in OHCs and 5 µm in IHCs.",
    "ncbi_link": "DIA1: 1729"
  },
  {
    "caption": "Loss of LRRC8D causes resistance to carboplatin and cisplatin, but not to oxaliplatin. Survival of parental, vector‐transduced, or LRRC8D‐deficient GT1 and GT2 KBM7 cells exposed for 96 h to increasing concentrations of cisplatin, carboplatin, and oxaliplatin. The corresponding IC50 values and 95% confidence interval (CI) are given in Appendix Table S2. Data are presented as mean ± SEM.",
    "ncbi_link": "LRRC8D: 55144"
  },
  {
    "caption": "A, BVRAC currents (ICl,vol) of the HAP1 (A) and KBM7 (B) haploid cell lines. Left panels, example current traces of ICl,vol fully activated by hypotonic cell swelling measured with the voltage‐clamp protocol shown in (A). Dashed lines indicate zero current. Right panels, averaged current/voltage relationships of maximally activated ICl,vol. Consistent with VRAC currents, they needed hypotonic swelling for activation, displayed an I− > Cl− permeability sequence, and were blocked by DCPIB (Appendix Fig S2A-H). The difference in current inactivation between HAP1 and KBM7 cells can be explained by the fact that KBM7 cells hardly express LRRC8E (Fig EV1) which accelerates VRAC inactivation (Voss et al, 2014). At potentials > +100 mV, also KBM7 currents inactivated (Appendix Fig S2I). Data are presented as mean ± SEM; n = 5-10.C",
    "ncbi_link": "LRRC8E: 80131"
  },
  {
    "caption": "LRRC8 subunit‐ and osmolarity‐dependent caspase induction in HCT116 cellsA, BCisplatin‐induced caspase activity in the continuous presence of 200 μM cisplatin under isotonic conditions (A), or after 1 h exposure to 200 μM cisplatin under iso‐ and hypotonic conditions (B), was followed over time in WT, HAP1−/−, LRRC8D−/−, and LRRC8 −/−HCT116 cells. Results from HAP1−/− and LRRC8D−/− were obtained with two different clonal cell lines each and averaged.CCaspase activation after 1‐h exposure to 4 μM staurosporine under iso‐ or hypotonic conditions of WT, HAP1−/−, LRRC8D−/−, and LRRC8 −/−HCT116 cells.Data information: Data are presented as mean ± SEM, n = 3-6. *P < 0.05; **P < 0.01; and ***P < 0.001. Similar results were obtained in three independent experiments. Fold change in (A) refers to t = 0. Control experiments indicated that hypotonicity per se had no effect (Appendix Fig S4).",
    "ncbi_link": "LRRC8D: 55144"
  },
  {
    "caption": "Carboplatin uptake into control KBM7 cells and two LRRC8D‐deficient clones (n = 6).",
    "ncbi_link": "LRRC8D: 55144"
  },
  {
    "caption": "Cisplatin uptake (200 μM) into HEK cells of indicated genotypes. LRRC8(B,C,E) −/− and LRRC8(B,D,E) −/− cells express only LRRC8A and LRRC8D, and LRRC8A and LRRC8C, respectively (n = 3 for WT, 6 for LRRC8D −/−, 9 for LRRC8A −/− in E; n = 3 in F).",
    "ncbi_link": "LRRC8A: 56262
LRRC8C: 84230
LRRC8D: 55144"
  },
  {
    "caption": "Cisplatin-DMSO inhibition of ICl,vol depends on the LRRC8D subunitUpper panel, example current traces (as in Fig 3A) of fully activated ICl,vol in HEK cells exposed to hypotonic solution containing vehicle (0.3% DMSO) or 200 μM cisplatin in 0.3% DMSO. Dashed lines indicate zero current. Lower panel, ICl,vol current densities (at −100 mV and 100 mV) of WT HEK cells treated with different cisplatin concentrations.No effect of 200 μM cisplatin/DMSO on ICl,vol in LRRC8D−/− HEK cells.Data information: Data are presented as mean ± SEM; the number of experiments is given for each bar; *P < 0.05; **P < 0.01.",
    "ncbi_link": "LRRC8D: 55144"
  },
  {
    "caption": "Swelling‐induced efflux of 3[H]‐taurine from WT and LRRC8D −/− HEK cells (A, B) and partial rescue by transient transfection of LRRC8D (B). Rescue is incomplete due to low transfection/expression efficiency of LRRC8D (Voss et al, 2014).",
    "ncbi_link": "LRRC8D: 55144"
  },
  {
    "caption": "(B) Phase-contrast images of wild-type or PABPC4KO HeLa cells depleted of PABPC1 by siRNA-mediated knockdown. Scale bar, 100 μm. (C) Total numbers of viable cells in (B) were quantified with acridine orange and propidium iodide staining and graphed as a percentage of wild-type HeLa cells. Error bars represent the SEM of three biological replicates.",
    "ncbi_link": "PABPC1: 26986
PABPC4: 8761"
  },
  {
    "caption": "(C) Phase-contrast images of PABPDHFR cells, or PABPDHFR cells transfected with a plasmid coding for wild-type PABPC1, 48 hours post-TMP removal. Scale bar, 100 μm.",
    "ncbi_link": "PABPC1: 26986"
  },
  {
    "caption": "(B) SUnSET assay of PABPDHFR cells grown in the presence or absence of TMP for 12 hours to maintain or deplete PABP. Cells were subsequently pulsed with either puromycin or puromycin and cycloheximide (control), lysed and equal protein amounts were resolved by SDS-PAGE. Western blot analysis was performed using a monoclonal antibody against puromycin or actin (loading control).",
    "ncbi_link": "DHFR: 944790
PABP: 26986"
  },
  {
    "caption": "(D) Scatter plot comparing log2 fold-changes [(-) PABP vs (+) PABP] in polysome-associated mRNA (y-axis) to corresponding changes in total cytoplasmic mRNA. Transcripts identified as regulated via altered translation efficiency (orange and red) or abundance (light and dark green) according to anota2seq are visualized together with non-regulated transcripts (grey).",
    "ncbi_link": "PABP: 26986"
  },
  {
    "caption": "Boxplots of 5´UTR (A), 3´UTR (B) lengths for mRNAs whose abundance decreased ('DOWN', dark green) or increased ('UP', light green) in PABP-depleted cells as compared to cells expressing PABP. Solid horizonal middle lines in box plots denote the median; lower and upper box limits correspond to first and third quartiles; whiskers extend from box limits to the most extreme values. Wilcoxon-Mann-Whitney tests (two-sided) were used to determine differences between upregulated mRNAs and downregulated mRNAs relative to each other and to the background (mRNAs whose abundance did not change in the absence of PABP relative to PABP-expressing cells).",
    "ncbi_link": "PABP: 26986"
  },
  {
    "caption": "(A) Boxplots of mRNA half-lives (hrs) assessed by metabolic labeling of normal human umbilical vein endothelial cells for mRNAs whose abundance decreased ('DOWN', dark green) or increased ('UP', light green) in PABP-depleted cells as compared to cells expressing PABP comparing (Tiana et al., 2020). Solid horizonal middle lines in box plots denote the median; lower and upper box limits correspond to first and third quartiles; whiskers extend from box limits to the most extreme values but not further than 1.5× the inter-quartile range (IQR). (B- H) PABPDHFR cells were cultured in the presence or absence of TMP for 12 hours. The stabilities of select mRNAs was assessed by using actinomycin D (5 μg/ml) for the indicated amounts of time. Total RNA was isolated, reverse transcribed with random hexamer oligonucleotide primers and quantified by qPCR. mRNA decay rates were normalized to an in vitro synthesized spike-in RNA with the zero time point set at 1. Error bars represent the SEM of three independent experiments. First order exponential decay trend lines were generated by non-linear regression analysis.",
    "ncbi_link": "DHFR: 944790
PABP: 26986"
  },
  {
    "caption": "(B) PABPDHFR cells were transfected with plasmids encoding RL-6xB or RL-6xBMUT. 24 hours after transfections, the cells were split and cultured for an additional 12 hours in the presence or absence of TMP. The stabilities of reporter mRNAs was assessed by using actinomycin D (5 μg/ml) for the indicated amounts of time. Total RNA was isolated, reverse transcribed with random hexamer oligonucleotide primers and quantified by qPCR. mRNA decay rates were normalized to an in vitro synthesized spike-in RNA with the zero time point set at 1. Error bars represent the SEM of three independent experiments. First order exponential decay trend lines were generated by non-linear regression analysis.",
    "ncbi_link": "RL-6xB: 
RL-6xBMUT: 
DHFR: 944790
PABP: 26986"
  },
  {
    "caption": "(A) Western blot analysis PABPDHFR cells depleted of LSM1, DCP2 or XRN1 by siRNA-mediated knockdown. siGFP represents a negative control.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(B) Phase-contrast images of PABPDHFR cells previously transfected with siRNAs targeting GFP (control), LSM1, DCP2 or XRN1 and cultured in the presence or absence of TMP for 48 hours. Total numbers of viable cells, denoted in the upper right hand corner of images, were quantified with acridine orange and propidium iodide and calculated as a percentage of PABPDHFR cells grown in the presence of TMP, along with the SEM. Scale bar, 100 μm.",
    "ncbi_link": "GFP: 
DCP2: 167227
LSM1: 27257
XRN1: 54464"
  },
  {
    "caption": "(C and D) Poly(A) tail analysis of GAPDH and ACTB mRNAs from total RNA isolated from PABPDHFR cells described in (B) was determined by extension poly(A) tail (ePAT). PCR products were run on high-resolution agarose gels. 'A12' represents the size of ePAT RT-PCR amplicons derived from a mRNA with a fixed (A12)-tail.",
    "ncbi_link": "ACTB: 60
DHFR: 944790
GAPDH: 2597
PABP: 26986"
  },
  {
    "caption": "Accumulation of Ub in autophagy-deficient brain. Ub profile from the 1% Triton X-100-soluble and -insoluble fraction of autophagy-deficient brain homogenates captured with P2UBA resin. (A) Age-matched control Atg7 littermates (Atg7flox/+;nestin-Cre:p62+/−; denoted +) at 6 wk (open circles; n = 4) or Atg7 KO (Atg7flox/flox;nestin-Cre:p62+/−; denoted −) at 6 wk (closed diamonds; n = 3) are shown.",
    "ncbi_link": "Cre: 
Atg7: 74244
nestin: 18008
p62: 18412"
  },
  {
    "caption": "Accumulation of Ub in autophagy-deficient brain. Ub profile from the 1% Triton X-100-soluble and -insoluble fraction of autophagy-deficient brain homogenates captured with P2UBA resin. (B) Control Atg5 littermates (Atg5flox/+;nestin-Cre; denoted +) at 16 (open circles; n = 4) and 26 wk (open diamonds; n = 3) or Atg5 KO (Atg5flox/flox;nestin-Cre; denoted −) at 16 (closed circles; n = 4) and 26 wk (closed diamonds; n = 3) are shown. Each symbol represents one animal. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.005.",
    "ncbi_link": "Cre: 
Atg5: 11793
nestin: 18008"
  },
  {
    "caption": "Suppressed accumulation of Ub in Atg7-/p62-deficient brains. (A and B) Quantitative mass spectrometry analysis of P2UBA captured total (A) and isopeptide-linked (B) Ub from the soluble and insoluble fractions of autophagy-deficient brains. Age-matched control Atg7 littermates (Atg7flox/+:nestin-Cre:p62+/−; denoted +) at 6 wk (open circles; n = 4), p62 KO (Atg7flox/flox:p62−/−; denoted −) at 6 wk (closed circles; n = 3), Atg7 KO (Atg7flox/flox:nestin-Cre:p62+/−; denoted −) at 6 wk (closed diamonds; n = 3), or Atg7-/p62-DKO (Atg7flox/flox:nestin-Cre:p62−/−) at 6 wk (closed triangles; n = 3) are shown. Each symbol represents one animal. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.005.",
    "ncbi_link": "Cre: 
Atg7: 74244
nestin: 18008
p62: 18412"
  },
  {
    "caption": "Suppressed accumulation of Ub in Atg7-/Nrf2-deficient livers. (A and B) Quantitative mass spectrometry analysis of P2UBA captured p62 (A), total (A), and isopeptide-linked (B) Ub from the soluble and insoluble fraction of autophagy-deficient livers (28 d after pIpC injection). Control littermates (F/F or F/F:Nrf2+/−; denoted +; open circles; n = 4), Nrf2 KO (F/F:Nrf2−/−; denoted −; closed circles; n = 4), Atg7 KO (F/F:Mx1 or F/F:Mx1:Nrf2+/−; denoted −; closed diamonds; n = 6), or Atg7-/Nrf2-DKO (F/F:Mx1:Nrf2−/−; closed triangles; n = 6) are shown. Each symbol represents one animal. **, P ≤ 0.01; ***, P ≤ 0.005.",
    "ncbi_link": "Atg7: 74244
Mx1: 17857
Nrf2: 18024"
  },
  {
    "caption": "(B) Elevated Ub mRNA levels from Atg5-deficient brains. Total RNA was extracted from control Atg5 littermates (Atg5flox/+;nestin-Cre) at 16 wk or Atg5 KO (Atg5flox/flox;nestin-Cre) at 16 wk (n = 4 for each genotype; **, P ≤ 0.01) and the amount of transcript from Ubc, Ubb, Uba52, and Uba80 genes was quantified using real-time RT-PCR and normalized to actin. Error bars indicate SEM. au, arbitrary unit.",
    "ncbi_link": "actin: 
Cre: 
Atg5: 11793
nestin: 18008
Uba80: 78294
Uba52: 22186
Ubb: 22187
Ubc: 22190"
  },
  {
    "caption": "(C) Western blot (WB) analysis of the accumulation of htt(Q)-GFP after autophagy shutoff. At steady-state (t = 0 h), the levels of both htt(Q25)-GFP and htt(Q47)-GFP were virtually undetectable. After autophagy shutoff, there was a robust increase in the level of htt(Q47)-GFP, as detected by GFP Western blot, whereas there was very little or no detectable increase in htt(Q25)-GFP, GAPDH, LDH, or chFP.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(D) Quantitative flow cytometry time course analysis measuring selective autophagy in live cells. The ASI is the ratio of the relative increase in green and red fluorescence, as assessed by two-color flow cytometry, in response to dox. In control experiments, the ASI of two soluble, nonaggregating proteins, htt(Q25)-GFP and chFP, was 1. In contrast, the ASI of the aggregation-prone protein, htt(Q47)-GFP, compared with chFP after autophagy shutoff (+dox; 100 h) was 2. Data represent three independent experiments performed on different days. **, P ≤ 0.01; ***, P ≤ 0.005.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(E) Flow cytometry time course analysis of cell death at different time points after autophagy shutoff (+dox). The degree of cell death correlated directly with increased htt(Q47)-GFP levels after autophagy shutoff and was significantly enhanced in cells expressing htt(Q47)-GFP compared with htt(Q25)-GFP (***, P ≤ 0.005). Data represent three independent experiments performed on different days.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(F) AQUA using heavy isotope-labeled GFP standard in addition to the routine Ub standards after P2UBA pull-down of soluble and insoluble lysates from htt(Q)-GFP-IRES-chFP bicistronic expressing cells before (−dox) and after autophagy shutoff (+dox). The experimental GFP peptide was only detected in two of the four experiments, and the data shown are representative of these. In the other two experiments, the experimental GFP peptide was below the threshold of detection.",
    "ncbi_link": "htt: 3064"
  },
  {
    "caption": "(A-F) Atg1‐induced myosin II activation depends on the kinase activity of Atg1. Third‐instar wing imaginal discs from ptc‐GAL4 UAS‐GFP controls or flies expressing indicated transgenes were stained with phospho‐MRLC (blue) and TRITC‐labelled phalloidin (red). Low level of phospho‐MRLC staining was observed in controls (A) and cells overexpressing kinase‐deficient Atg1‐KR (C), whereas a robust increase in phospho‐MRLC was found in cells overexpressing Atg1 (B). Co‐expression of Atg1 and spaghetti‐squash (A20A21) exhibited low level of phospho‐MRLC staining (D). Atg1‐induced high level of phospho‐MRLC staining was not suppressed by expression of caspase inhibitor p35 (E) or by depletion of Atg12 (Atg12RNAi) (F). Bar, 20 μm.",
    "ncbi_link": "GAL4: 
p35: 
Atg1: 39454
Atg12: 39383
ptc: 35851
spaghetti‐squash: 31554"
  },
  {
    "caption": "(H) Sqa, but not Atg1, directly phosphorylated Sqh in vitro. Flag-Atg1, Flag-Atg1‐KR, HA-Sqa and HA-Sqa‐KA were immunoprecipated from lysate of transfected cells and incubated in an in vitro kinase reaction mixture containing [γ‐32P]ATP and bacterially expressed recombinant wild‐type Sqh or SqhA20A21. As shown on the autoradiogram (top panel), wild‐type but not the kinase‐deficient Atg1 (Atg1‐KR) and Sqa (Sqa‐KA) was autophosphorylated. No phosphorylation was seen with SqhA20A21. The equal input of His‐fusion proteins is shown on the Coomassie staining. Anti‐Flag and anti‐HA immunoblottings (IBs) were used as controls to quantify the amount of proteins precipitated.",
    "ncbi_link": "Atg1: 39454
Sqa: 36002
Sqh: 31554"
  },
  {
    "caption": "(A-K) Genetic interactions between Atg1, Sqa, and spaghetti‐squash (Sqh). Compared with the ptc‐GAL4 controls (A), expression of Atg1 or Sqa by ptc‐GAL4 resulted in missing anterior cross‐vein phenotypes (B, C). However, RNAi‐mediated downregulation of Atg1 (Atg1RNAi) or Sqa (SqaRNAi) did not cause wing vein defects (D, E). Depletion of Atg1 and Sqa suppressed Atg1 and Sqa‐induced wing vein defects, respectively (F, I). Atg1‐induced wing defects were modulated by depletion of Sqa (G) or by co‐expression of SqhA20A21 (H). Nevertheless, Sqa‐induced wing vein defects were suppressed by co‐expression of SqhA20A21 (J) but not Atg1RNAi (K).",
    "ncbi_link": "GAL4: 
Atg1: 39454
ptc: 35851
Sqa: 36002
spaghetti‐squash: 31554
Sqh: 31554"
  },
  {
    "caption": "(M) 293T cells were transfected with HA‐tagged Sqa WT (wild‐type) or KA, together with Flag‐tagged Atg1 WT or KR. The cells were lysed 48 h after transfection and immunoprecipitated (IP) with anti‐Flag antibodies. The immunoprecipitated proteins and the total cell lysates (TCL) were analysed by immunoblotting (IB) with antibodies as indicated.",
    "ncbi_link": "Sqa: 36002
Atg1: 8408"
  },
  {
    "caption": "(N) 293T cells transfected with Flag-Atg1‐KR and various HA‐tagged Sqa contracts were subjected to immunoprecipitations with anti‐HA antibody. The immunoprecipitated proteins and the total cell lysates were analysed by immunoblotting with antibodies as indicated.",
    "ncbi_link": "Sqa: 36002
Atg1: 8408"
  },
  {
    "caption": "(O) Atg1 directly phosphorylated Sqa in vitro. Flag‐tagged Atg1 WT or KR immunoprecipated from lysate of transfected cells was used to phosphorylate bacterially expressed recombinant Sqa‐K1, Sqa‐K2, and Sqa‐C in an in vitro kinase assay. The lower panels represent equal input of His‐fusion proteins and Atg1 immunoprecipitates.",
    "ncbi_link": "Atg1: 39454
Sqa: 36002"
  },
  {
    "caption": "(A) Characterization of Atg1‐dependent phosphorylation sites on Sqa. 293T cells transfected with Flag‐tagged Atg1 or Atg1‐KR were subjected to immunoprecipitation with anti‐Flag antibodies, followed by in vitro kinase assays with bacterially expressed Sqa‐K2, Sqa‐K2‐T194A, Sqa‐K2‐T239A, and Sqa‐K2‐T279A as substrates. Atg1 but not Atg1‐KR was autophosphorylated (top panel). Relative phosphorylation levels of substrates were quantified. Data are represented as mean±s.e. of triplicates. (B-D) Phosphorylation of Sqa at Thr‐279 is critical for the kinase activity of Sqa.",
    "ncbi_link": "Atg1: 39454
Sqa: 36002"
  },
  {
    "caption": "(B) HA‐tagged Sqa or Sqa‐T279A immunoprecipated from lysate of transfected cells was used to phosphorylate bacterially expressed recombinant spaghetti‐squash (Sqh) WT and A20A21, in an in vitro kinase assay.",
    "ncbi_link": "Sqa: 36002
Sqh: 31554"
  },
  {
    "caption": "(C) Clonal expression of Sqa but not Sqa‐T279A (GFP‐positive cells) in the larval wing imaginal discs resulted in a marked increase in phospho‐MRLC staining (blue) and actin reorganization (red). Bar, 20 μm.",
    "ncbi_link": "Sqa: 36002"
  },
  {
    "caption": "(A, B) Activation of myosin II on nutrient deprivation. The larval fat body of denoted genotypes under fed or starved conditions were dissected, lysed, and subjected to western blot analysis using antibodies specific for phospho‐myosin regulatory light chain (MRLC) and total MRLC. The Rheb, SqaRNAi, Sqa‐T279A, spaghetti‐squash (SqhA20A21), and Atg7RNAi transgenes were expressed under the control of hs-GAL4 driver (B). For quantification, the relative phosphorylation levels of MRLC were quantified as in Figure 3D. Data are represented as mean±s.e. of triplicates.",
    "ncbi_link": "GAL4: 
Atg7: 37141
Rheb: 117332
Sqa: 36002
Sqh: 31554"
  },
  {
    "caption": "(C-J) Starvation‐induced autophagosome formation was compromised by inhibition of myosin II activation. Compared with the fed condition (C), starvation induced a robust formation of GFP-Atg8a puncta in larval fat‐body cells (D). Clonal expression of Atg12RNAi (E), Sqa‐T279A (F), SqaRNAi (G), or SqhA20A21 (H) markedly suppressed GFP-Atg8a puncta formation during starvation. The autophagic defects caused by Sqa‐T279A and SqaRNAi were rescued by co‐expression of the constitutively active SqhE20E21 (I) and SqhD20D21 (J), respectively. Bar, 20 μm.",
    "ncbi_link": "Atg12: 39383
Sqa: 36002
Sqh: 31554"
  },
  {
    "caption": "(L) Inhibition of myosin II activity increased sensitivity to starvation. Flies carrying transgenes under the control of fat body‐specific Cg-GAL4 driver were used for further analysis. Histogram illustrating the survival curve of adult female flies of denoted genotypes when placed under starved conditions. Data are mean±s.e. from triplicate experiments (n=100 flies/genotype/treatment). *P0.05, **P0.01, ***P0.001. See Supplementary data for genotypes.",
    "ncbi_link": "GAL4: 
Cg: 36571"
  },
  {
    "caption": "(A) Ulk1 interacted with ZIPK. 293T cells transfected with HA‐tagged ZIPK together with Flag‐tagged Ulk1 or Ulk1‐KI were subjected to immunoprecipitations with anti‐Flag antibody. The immunoprecipitated proteins and the total cell lysates were analysed by immunoblotting with antibodies as indicated.",
    "ncbi_link": "ZIPK: 1613
Ulk1: 8408"
  },
  {
    "caption": "(B) HA‐tagged kinase‐inactive ZIPK‐KA (K42A) was expressed in 293T cells with Flag‐tagged Ulk1 or Ulk1‐KI. Cell lysates were incubated with or without alkaline phosphatase (CIP) and analysed by immunoblotting with antibodies as indicated.",
    "ncbi_link": "ZIPK: 1613
Ulk1: 8408"
  },
  {
    "caption": "(D) MCF7 cells stably infected with lentivirus expressing control (shLuc), Ulk1 or ZIPK shRNA were cultured in nutrient‐rich DMEM medium (F) or EBSS (S) for 2 h. Effects of Ulk1 and ZIPK knockdown on starvation‐induced myosin II activation were analysed by immunoblotting with antibodies as indicated. Data are mean±s.e. of triplicates.",
    "ncbi_link": "ZIPK: 1613
Ulk1: 8408"
  },
  {
    "caption": "(A) MCF7/GFP-LC3 cells stably infected with lentivirus expressing control (shLuc), ZIPK, or non‐muscle myosin heavy chain‐IIA (NMHC‐IIA) shRNA were cultured in nutrient‐rich medium (DMEM) or starvation medium (Earle's balanced salt solution; EBSS) in the presence or absence of lysosomal inhibitor bafilomycin A1 (BafA1) for 2 h. Depletion of ZIPK and NMHC‐IIA markedly inhibited starvation‐induced GFP-LC3 puncta formation. Quantification of the number of GFP-LC3 dots per cell (lower panel) was shown (data are represented as mean±s.e. of 100 cells, ***P0.001).",
    "ncbi_link": "ZIPK: 1613
NMHC‐IIA: 4627"
  },
  {
    "caption": "(B) Cells as in (A) were cultured in nutrient‐rich medium (F) or EBSS (S) with or without BafA1 for 2 h. Effects of ZIPK and NMHC‐IIA knockdown on starvation‐induced GFP-LC3 conversion were assessed by immunoblotting with anti‐LC3, anti‐ZIPK, anti‐NMHC‐IIA, and anti‐tubulin antibodies. The relative ratio of LC3II/LC3I is shown at the right panel. Data are mean±s.e. of triplicates.",
    "ncbi_link": "ZIPK: 1613
NMHC‐IIA: 4627"
  },
  {
    "caption": "(A) The fat body of spaghetti‐squash (sqhAX3); sqh-GFP larva under fed or starved conditions were dissected and subjected to immunofluorescence analysis. Sqh-GFP and phospho‐myosin regulatory light chain (MRLC) were enriched in cell-cell junction under nutrient‐rich (fed) condition. Under starvation conditions, Sqh-GFP and phospho‐MRLC were localized to both cell-cell junction and perinuclear region. Actin was stained with TRITC‐labelled phalloidin (red) and nucleus was stained with DAPI (blue). Bar, 20 μm.",
    "ncbi_link": "spaghetti‐squash: 31554
Sqh: 31554
sqh: 31554"
  },
  {
    "caption": "(C) MCF7/GFP-LC3 cells cultured in nutrient‐rich (DMEM) or starved (EBSS) conditions were homogenized and subjected to centrifugation, and the resulting post‐nuclear supernatant (PNS) was fractionated by high‐speed centrifugation into membrane pellet and cytosol. Proteins were resolved by SDS-PAGE and immunoblotted with anti‐TGN46 antibody as a control for membrane‐association proteins, anti‐caspase‐3 as a control for cytosolic proteins. The levels of phospho‐MRLC and MRLC in each fraction were quantified using ImageJ and plotted relative to their amounts in PNS (n=3). Each value represents mean±s.e. of three experiments. *P0.05, **P0.01.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) Immunofluorescence analysis of GFP-mAtg9 and phospho‐myosin regulatory light chain (MRLC) in MCF7/GFP-mAtg9 cells. GFP-mAtg9 was enriched in the trans‐Golgi network (TGN) labelled with anti‐TGN46 antibody and phospho‐MRLC localized to cell peripheral in nutrient‐rich condition (DMEM). GFP-mAtg9 redistributed and co‐localized with phospho‐MRLC in starvation condition (Earle's balanced salt solution; EBSS).",
    "ncbi_link": "Atg9: 285973///79065"
  },
  {
    "caption": "(B) mAtg9 interacted with non‐muscle myosin heavy chain‐IIA (NMHC‐IIA) under starvation conditions. 293T cells (right panel) or 293T cells stably infected with lentivirus expressing control (shLuc), UNC‐51‐like kinases (Ulk1) or zipper‐interacting protein kinase (ZIPK) shRNA (left panel) were transfected with V5‐tagged mAtg9 and GFP-tagged NMHC‐IIA. At 48 h after transfection, cells were incubated in either serum‐containing medium (DMEM) or EBSS for 2 h with or without the treatment of 50 μM ML‐7 and blebbistatin (Blebb). Cell lysates were immunoprecipitated with anti‐V5 antibody and immunoblotted with indicated antibodies.",
    "ncbi_link": "Atg9: 285973///79065
ZIPK: 1613
NMHC‐IIA: 4627
Ulk1: 8408"
  },
  {
    "caption": "(C) MCF7/GFP-mAtg9 cells were stably infected with lentivirus expressing control (shLuc), ZIPK, or NMHC‐IIA shRNA. Under starved conditions, mAtg9 was redistributed from the TGN to a dispersed peripheral pool in control cells (shLuc). Starvation‐induced GFP-mAtg9 redistribution was blocked in ZIPK and NMHC‐IIA knockdown cells. The images were analysed by quantifying mAtg9 localization in cells for either a TGN‐enriched or dispersed pattern. Data are represented as mean±s.e. of 70 cells. *P0.05, **P0.01. Bar, 10 μm.",
    "ncbi_link": "Atg9: 79065///285973
ZIPK: 1613
NMHC‐IIA: 4627"
  },
  {
    "caption": "(a) Representative micro-CT pictures of hind legs of 20-30 week-old control (A20WT) and A20myel-KO littermates. Note the severe osteoporosis in A20myel-KO mice. (b) Trabecular parameters, calculated on micro-CT scans of hind legs of 20-30 week-old control (A20WT) and A20myel-KO littermates. Each dot represents an individual mouse (A20WT, n=10; A20myel-KO, n=8).",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(a) Levels of TNF and IL-6 in serum of A20WT, A20OC-KO and A20myel-KO mice. Each dot represents an individual mouse (A20WT, n=11; A20OC-KO, n=11 and A20myel-KO, n=14). Data are expressed as mean ± SEM. *",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(c) Trabecular parameters, calculated on micro-CT scans of hind legs of 20-30 week-old control (A20WT) and A20OC-KO littermates. Each dot represents an individual mouse (A20WT, n=6; A20OC-KO, n=9).",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(e) Representative pictures of TRAP-stained sections from tibia of 20 week-old A20WT and A20OC-KO mice. Red arrows indicate osteoclasts.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(f) Quantification of the number of TRAP-positive cells on sections from tibia of 20 week-old A20WT and A20OC-KO mice. Each dot represents an individual mouse (A20WT, n=5; A20OC-KO, n=6).",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(d) Measurement of NF-κB luciferase activity in lysates of HEK293T cells transiently transfected with an NF-κB reporter plasmid, an expression plasmid for β-galactosidase (βgal), an expression plasmid for RANK, and with either an empty vector or a vector expressing wild-type A20. Cell lysates were analysed for luciferase and βgal activity and values are plotted as Luc/βgal to normalize for possible differences in transfection efficiency.",
    "ncbi_link": "Luc: 
A20: 7128
RANK: 8792"
  },
  {
    "caption": "(e) Western blot analysis of whole cell lysates from BMDMs cultures isolated from A20WT and A20myel-KO mice and stimulated with RANKL (100ng/ml) for the indicated time periods. Actin is shown as a loading control.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(f) Wild-type and A20 deficient BMDMs were stimulated with GST-RANKL (1 μg/ml) for the indicated time periods. The RANK signaling complex was immunoprecipitated using glutathione-sepharose beads and immunoblotted for RANK, A20, TRAF6, HOIP and Sharpin.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(g) BMDMs from A20WT and A20myel-KO mice were stimulated with RANKL (100ng/ml) for the indicated time periods and immunoblotted to visualize p100 processing to p52. Actin is shown as a loading control.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(a) Measurement of NF-κB luciferase activity in lysates of HEK293T cells transfected with an NF-κB luciferase reporter plasmid, an expression plasmid for β-galactosidase (βgal), an expression plasmid for RANK, and plasmids encoding different A20 variants: A20WT, A20DUB (C103A mutation), A20ZnF4 (C624A/C627A), A20ZnF7 (C775A/C779A), and A20ZnF4ZnF7 (C624A/C627A/C775A/C779A). Cell lysates were analysed for luciferase and βgal activity and values are plotted as Luc/βgal to normalize for possible differences in transfection efficiency. Data are expressed as the mean of technical triplicates ± SD.",
    "ncbi_link": "Luc: 
luciferase: 
A20: 7128
RANK: 8792"
  },
  {
    "caption": "(c-d) Western blot analysis of whole cell lysates from BMDMs differentiated from A20WT and A20ZnF4ZnF7 mice, stimulated with RANKL (100ng/ml) for the indicated time periods. Actin is shown as a loading control.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "(e) BMDMs isolated from control (A20WT), A20ZnF7, A20ZnF4ZnF7 and A20DUB mice were stimulated with GST-RANKL (1 μg/ml) for the indicated time periods. The RANK signaling complex was immunoprecipitated using glutathione-sepharose beads and immunoblotted for A20. Actin was used as a loading control.",
    "ncbi_link": "A20: 21929"
  },
  {
    "caption": "A. Traces showing average changes (mean±s.e.m.) in  intracellular Ca2+ (Fura2 ratio) over time in response to perfusion of different [Ca2+]o as indicated in the upper bar in MEF Stim1/Stim2-/- cells transfected with Stim1- (black trace, n=111), Stim1A (red trace, n=116), the combination Stim1 with Stim1A (blue trace, n=86) or with vector only (grey trace, n=79). B. Quantification of changes in ratio of resting,  influx rate (Δratio/time), Δpeak and Δplateau measured in A. *** p<0.001, Kruskal-Wallis Anova. C. Traces showing average changes (mean±s.e.m.) in   intracellular Ca2+  (Fura 2 ratio) in  HEK293 cells co-transfected with  Orai1    and either Stim1- (black trace, n=119) or Stim1A  IRES-mCherry (red trace, n=118). D. Quantification of changes in ratio of resting, influx rate (Δratio/time), Δpeak and Δplateau measured in C. ** p<0.01 *** p<0.001 Mann-Whitney test. E. Data information: Data were obtained from three biological replicates (e.g. transfections) with each three measured dishes (technical replicates) with multiple cells each (yielding a total number n) and is shown as mean±s.e.m.",
    "ncbi_link": "mCherry: 
Orai1: 84876
Stim1: 20866
Stim1: 6786
Stim1A: 20866
Stim1A: 6786
Stim2: 116873"
  },
  {
    "caption": "B. Traces showing average changes (mean±s.e.m.) in  intracellular Ca2+ (Fura2 ratio) over  time  in response to perfusion of different [Ca2+]o as indicated in the upper bar with constructs as indicated expressed in HEKO1.  STIM1  (black, n=145), STIM1A  (red, n=157) and STIM1A_D503A (n=185). C. Relative fluorescence intensities of mCherry-tagged constructs measured in (B). D. Quantification of changes in resting ratio, TG  peak (∆ ratio) and SOCE parameters measured in B. E. Data information: *P<0.05, **P<0.01 ***P<0.001 Kruskal-Wallis Anova with Dunn's multiple comparisons test. Data points (total n) were obtained from three biological replicates with each three technical replicates (each multiple cells) and shown as mean±s.e.m for traces and as scatter plots with the underlying boxes showing the means for individual parameters.",
    "ncbi_link": "O1: 84876
STIM1: 6786
STIM1A: 6786"
  },
  {
    "caption": "E. Average traces showing  whole-cell  current density  (CD) over  time extracted at -80 mV in HEKO1  cells transfected with  STIM1 (black),  STIM1A (red) or  STIM1A_D503A (blue). F. Average maximum  CDs recorded from cells measured in E (n within bars). G Data information: *P<0.05, **P<0.01 ***P<0.001 Kruskal-Wallis Anova with Dunn's multiple comparisons test. Data points (total n) were obtained from three biological replicates with each three technical replicates (each multiple cells) and shown as mean±s.e.m for traces and as scatter plots with the underlying boxes showing the means for individual parameters.",
    "ncbi_link": "O1: 84876
STIM1: 6786
STIM1A: 6786"
  },
  {
    "caption": "F. Traces showing average changes (mean±s.e.m.) in  intracellular Ca2+ (Fura2 ratio) over  time in response to perfusion of different [Ca2+]o as indicated in the upper bar with constructs as indicated expressed in HEKS1/S2-/-. G. Quantification of the relative reduction of ratio/time  or ratio for cells (135 H Data information: , ***P<0.001, Kruskal-Wallis Anova with Dunn's multiple comparisons test Data points (total n) were obtained from three biological replicates with each three technical replicates (with multiple cells) and shown as mean±s.e.m for traces (F) and as scatter plots with the underlying boxes showing the means for individual parameters (G).",
    "ncbi_link": "S1: 6786
S2: 57620"
  },
  {
    "caption": "H,I. Average traces (mean±s.e.m.) showing  whole- cell current density (CD) over  time extracted at -80 mV in in HEKS1/S2-/- cells co-transfected either with STIM1  (black) or STIM1A (red) and ORAI1 (H) or with ORAI1  R77E (I) and recorded using extracellular solution containing 2 mM  Ca2+. J. Average maximum  CDs recorded from cells measured in [H,I] (n within bars). Data information: I , *P<0.05, **P<0.01, unpaired T test with Welch's correction. For patch-clamp experiments, number in bars indicate measured cells, which were from three independent transfections.",
    "ncbi_link": "ORAI1: 84876
S1: 6786
STIM1: 6786
STIM1A: 6786
S2: 57620"
  },
  {
    "caption": "B. Hits from (A) tested for interaction  with commercially available constructs quantified with  bimolecular fluorescence complementation (BiFC) via  flow cytometry. HEKS1/S2-/- were transfected with  STIM1-YFPC (black) or STIM1A-YFPC (red) in combination with POI-YFPN and screened for YFP+ cells via  FACS, results (mean ± SD) from three transfections with each 10.000 sorted cells.",
    "ncbi_link": "YFP: 
S1: 6786
STIM1: 6786
STIM1A: 6786
S2: 57620"
  },
  {
    "caption": "D. Ratio  nuclear NFAT-GFP  vs. cytosolic GFP  intensity normalized to t=0 (mean±s.e.m.) after transfection of SH-SY5Y S1-/- cells with STIM  (n=42), STIM1A (n=82), STIM1A_D503A (n=49) or vector only (ØSTIM, n=15) IRES mCherry and induction of SOCE after stimulation with 1 µM TG. Data (total n as indicated) from at least three independent transfections.",
    "ncbi_link": "mCherry: 
STIM: 6786
S1: 6786
STIM1A: 6786"
  },
  {
    "caption": "A. Time course  of translocation (Nuclear NFAT-GFP signal/cytosolic signal normalized to TG addition at t=0, mean±s.e.m, for each time point) after transfection of indicated constructs and preincubation with 1 µM PF-04957325 (analyzed cells: STIM1 + PF n = 75, STIM1A + PF  n = 50, ØSTIM + PF n = 9) Data (total n as indicated) from at least three independent transfections. * p< 0.05, **p<0.01, ***p<0.001, Kruskal-Wallis Anova with Dunn's multiple comparisons test. B. PF-04957325 induced difference of the  nuclear NFAT-GFP signal vs. cytosolic signal from (A) to mean of control without the blocker (see Fig. 6D). * p< 0.05, **p<0.01, ***p<0.001,Mann-Whitney test of differences.. C Data information: *p<0.05, **p<0.01, ***p<0.001, 2way Anova Data (total number of cells, n) were obtained from at least three independent transfections with several technical replicates each.",
    "ncbi_link": "STIM: 6786
STIM1: 6786
STIM1A: 6786"
  },
  {
    "caption": "C. Endpoint value with addition of PF or indicated cAMP analoga loaded for 30 min as AM esters before the experiment, shown as mean±s.e.m , ØSTIM + 6Bnz-cAMP/8-pCPT-cAMP n = 15/14 cells; STIM1  +  6Bnz-cAMP/8-pCPT-cAMP: n = 87/66, STIM1A + 6Bnz-cAMP : n = 78/67; from three independent transfections. Data information: *p<0.05, **p<0.01, ***p<0.001, , Kruskal-Wallis Anova with Dunn's multiple comparison test Data (total number of cells, n) were obtained from at least three independent transfections with several technical replicates each.",
    "ncbi_link": "STIM: 6786
STIM1: 6786
STIM1A: 6786"
  },
  {
    "caption": "G. Normalized fluorescence signal change (mean±s.e.m) of  R-FlincA, SH-SY5Y S1-/- cells expressing STIM1 (n=20) or  STIM1A  (n=22) IRES  GFP variants and the indicator were stimulated by TG (1 μM). To avoid photobleaching, values were only recorded after 5 and 30 min, respectively The mutant R-Flinc (n=15) was measured in SH-SY5Y  wt cells after TG stimulation. Data information: *p<0.05, **p<0.01, ***p<0.001, Kruskal-Wallis Anova with Dunn's multiple comparison test Data (total number of cells, n) were obtained from at least three independent transfections with several technical replicates each.",
    "ncbi_link": "GFP: 
S1: 6786
STIM1: 6786
STIM1A: 6786"
  },
  {
    "caption": "Rfa1-TAP purification was performed using Rfa1-TAP rtt105∆ strains expressing WT and indicated Rtt105 mutant forms. pRS313 serves as vector control (Vc).",
    "ncbi_link": "rtt105: 856841
Rtt105: 856841"
  },
  {
    "caption": "Snapshots of Rfa1 ChIP-Seq peak at ARS305 from WT and rtt105∆ cells released into HU-medium. The average Rfa1 ChIP-Seq read density from cells released into HU-medium around ACS sites. ACS: ARS consensus sequence.",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "The nuclear localization of Rfa1 proteins is altered in rtt105∆ mutant cells. Rfa1 tagged with GFP at its C terminus was used to analyze the localization of Rfa1-GFP fusion protein (Green) and the nuclear envelop is visualized with the Nup49-mCherry fusion protein (Red) using fluorescence microscopy. DIC: differential interference contrast. Scale bar: 5μm.",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "NLS-RFA1-GFP rescues the nuclear localization of Rfa1 in rtt105∆ mutant cells. The wild type RFA1 gene was fused with an SV40 large T Antigen nuclear localization sequence (NLS) at its 5'-end and a GFP gene at its 3' end to obtain a construct, driven by the RFA1 promoter to express NLS-RFA1-GFP fusion protein. The engineered construct was then transformed into WT or rtt105∆ mutant yeast cells to replace its endogenous RFA1 expression. The resulting yeast cells were then visualized under microscope, and GFP signals enriched in the nuclei were scored. RFA1-GFP lacking the NLS sequence was transformed into rtt105∆ rfa1∆ mutant cells as a control. DAPI staining indicates nuclear DNA.",
    "ncbi_link": "GFP: 
RFA1: 851266
rfa1: 851266
rtt105: 856841
large T Antigen: 29031019"
  },
  {
    "caption": "An increase in nuclear localization of Rfa1 could not rescue the RPA binding defects at the replication regions in rtt105∆ cells. The percentage of Rfa2 ChIP-DNA over the total input DNA was calculated. The mean and standard error (SE) of three biological replicates were shown. Statistical significance was evaluated based on Student's t-tests (*: 0.01≤P value<0.05).",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "An increase in nuclear localization of Rfa1 could not rescue the RPA binding defects at the replication regions in rtt105∆ cells. The percentage of Rfa2 ChIP-DNA over the total input DNA was calculated. The mean and standard error (SE) of three biological replicates were shown. Statistical significance was evaluated based on Student's t-tests (*: 0.01≤P value<0.05).",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "Rad52-GFP foci were counted in WT and rtt105∆ cells, the percentage of cells with Rad52-foci is reported. Error bars indicate one standard deviation from three independent experiments with at least 150 cells counted in each replicate.",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "Rad53 phosphorylation was analyzed in WT and rtt105∆ cells by immunoblotting of protein extracts with anti-Rad53 antibodies. Ponceau S (Pon S) staining was applied as a loading control.",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "Deletion of RTT105 leads to an increased rate of gross chromosomal rearrangements (GCRs). Wild-type (WT) and rtt105∆ mutant strains integrated with the yWSS439-5ori∆ yeast artificial chromosomes (YACs). GCRs rates in the evaluation of telomere marker loss were assayed",
    "ncbi_link": "YACs: 
yeast artificial chromosomes: 
RTT105: 856841
rtt105: 856841"
  },
  {
    "caption": "Ten-fold serial dilutions WT or rtt105∆ cells in two different backgrounds were assayed on normal growth media (YPD) and on media containing the indicated DNA damaging agents, methyl-methane sulfonate (MMS), camptothecin (CPT), bleomycin (Bleo), and hydroxyurea (HU).",
    "ncbi_link": "rtt105: 856841"
  },
  {
    "caption": "C. Effect of Nox4 on the unfolded protein response. Nox4 was depleted in H9c2 cells by shRNA-mediated knockdown (Ad.shNox4) or cells were treated with a control adenovirus (Ad.Ctl). In cells with Nox4 knockdown, tunicamycin treatment resulted in lower increases in protein levels of the ER chaperones Grp94, Grp78 and calreticulin than in conrol cells. Nuclear protein levels of ATF4 were substantially lower in Nox4-depleted cells than control cells but the levels of cleaved ATF6 (ATF6c) were similar. Histone was used as a loading control. The relative mRNA levels of Xbp1-s (a readout of IRE1 signaling) were unaltered after Nox4 knockdown. Mean data are shown in Appendix Fig S1E. Similar results were obtained with an independent siRNA approach (Appendix Fig S2A).D. Effect of adenoviral-mediated overexpression of Nox4 (Ad.Nox4) or a control β-galactosidase protein (Ad.β-Gal) on tunicamycin responses of H9c2 cells. Nox4 enhanced the increase in cellular ER chaperones and nuclear ATF4 levels but did not affect tunicamycin-induced changes in nuclear ATF6c levels and caused minor reduction in Xbp1s mRNA levels. Mean data are shown in Appendix Fig S2B.",
    "ncbi_link": "β-Gal: 
β-galactosidase: 
Nox4: 85431
Xbp1: 289754"
  },
  {
    "caption": "E,F. Effect of Nox4 knockdown or overexpression, respectively, on the tunicamycin-induced changes in mRNA levels of ATF4 target genes. n=4/group. Psat1, phosphoserine aminotransferase; Phgdh, 3-phosphoglycerate dehydrogenase; Asns, asparagine synthetase; Slc6a9, glycine transporter 1.",
    "ncbi_link": "Asns: 25612
ATF4: 79255
Nox4: 85431
Phgdh: 58835
Psat1: 293820
Slc6a9: 116509"
  },
  {
    "caption": "G. Effect of ATF4 silencing with two different siRNAs on Nox4 protein levels in tunicamycin-treated H9c2 cells. Scrambled siRNAs were used as a control (Ctl). Representative immunoblots shown to the top (captions at bottom of bar graphs refer also to the immunoblots); tubulin was used as a loading control. n=4/group. *, significant compared to baseline; #, significant comparing siATF4 versus corresponding siCtl.",
    "ncbi_link": "ATF4: 79255"
  },
  {
    "caption": "H. Effect of ATF4 overexpression on Nox4 mRNA and protein levels. n=3/group.",
    "ncbi_link": "ATF4: 79255"
  },
  {
    "caption": "A. The knockdown of endogenous Nox4 resulted in a substantial inhibition of tunicamycin-induced eIF2a phosphorylation in H9c2 cells, with no change in phospho-Thr980-PERK (PERK-P) levels. GADD34 levels were significantly decreased after Nox4 knockdown while there was no change in PP1 protein levels.B. Overexpression of Nox4 in H9c2 cells caused prolongation of tunicamycin-induced eIF2a phosphorylation, with minimal change in phospho-PERK levels.C,D. Mean levels of phosphorylated eIF2a relative to total eIF2a protein in tunicamycin-treated cells after Nox4 knockdown or overexpression, respectively. n=3/group. *, significant compared to baseline; #, significant comparing Nox4 knockdown (Ad.shNox4) or overexpression (Ad.Nox4) versus corresponding controls (Ad.Ctl or Ad.β-Gal, respectively).",
    "ncbi_link": "β-Gal: 
Nox4: 85431"
  },
  {
    "caption": "E,F. Effect of Nox4 knockdown or overexpression, respectively, on okadaic acid-resistant Ser/Thr phosphatase activity in membrane fractions of tunicamycin-treated H9c2 cells. n=4/group. *p<0.05, **p<0.01 cf. baseline; #, p<0.05, ##, p<0.01 comparing Nox4 knockdown (Ad.shNox4) or overexpression (Ad.Nox4) versus corresponding controls (Ad.Ctl or Ad.β-Gal, respectively).",
    "ncbi_link": "β-Gal: 
Nox4: 85431"
  },
  {
    "caption": "G,H. Nox4 knockdown or overexpression, respectively, had no effect on the phosphorylation of glycogen synthase at Ser641 (GS-P) or Histone H3 at Ser57 (H3-P) in H9c2 cells.",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "I. Nox4-/- MEF cells (KO) showed blunted tunicamycin-induced increases in levels of phospho-eIF2a, ATF4 and ER chaperones as compared to wild-type (WT) MEFs, a response that was rescued by re-introduction of Nox4 (KO+Nox4). The latter had no effect on GS-P or H3-P levels.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "E. The association of Nox4 with GADD34 was validated in HEK293 cells co-transfected with Nox4 and either Flag-tagged or non-tagged GADD34, followed by IP with an anti-Flag antibody.",
    "ncbi_link": "Nox4: 50507
GADD34: 17872"
  },
  {
    "caption": "F. Co-transfection of HEK293 cells with GADD34-Flag and different myc-tagged Nox4 constructs, followed by IP with an anti-myc antibody. GADD34 binds to full-length Nox4 (FL) and the Nox4 transmembrane domain (TD) but not the C-terminal domain (CD).",
    "ncbi_link": "Nox4: 50507
GADD34: 17872"
  },
  {
    "caption": "G. Representative pseudocolor images of simultaneous ER and cytosolic ROS measurement with HyPer ER and HyPerRed Cyto, respectively, in tunicamycin-treated MEF cells. Redox-insensitive mutant probes were used as negative controls and to exclude pH changes. Extracellular H2O2 (200 nM) was added as a positive control. The pseudocolor scale is shown along the left vertical edge of each image. KO = Nox4-/-. Scale bars, 2 µm.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "H. Transfection of HEK293 cells with PP1 and GADD34 increased PP1 activity (bar graph) and decreased phospho-eIF2 levels (immunoblots). Co-transfection of full-length Nox4 reduced PP1 activity and increased phospho-eIF2 levels (captions at bottom refer both to the bar graphs and immunoblots). These effects were abrogated when either Nox4 P437H or the Nox4 transmembrane domain (TD) were transfected. Nox4 did not affect phosphorylation of glycogen synthase (GS-P) or histone H3 (H3-P). All experiments were n=3/group. Values below the immunoblots are mean ± SEM levels for phospho-eIF2/total-eIF2. *, p<0.05 comparing third and fourth lanes; Levels of significance for comparisons of PP1 activities are shown above the bar columns. See also Fig EV1 and Appendix Fig S4.",
    "ncbi_link": "Nox4: 50507
PP1: 5501
GADD34: 17872"
  },
  {
    "caption": "A. Recombinant PP1 was inhibited by H2O2 (0.2 mM) and activity was not restored by glutathione (GSH), cysteine (Cys) or dithiothreitol (DTT). A Cys127Ser/Cys273Ser PP1 mutant was inhibited by H2O2 similarly to wild-type PP1. Values above bars denote level of significance for the inhibitory effect of H2O2.",
    "ncbi_link": "PP1: 5501"
  },
  {
    "caption": "E. Effect of Nox4 on GADD34/PP1-mediated eIF2 dephosphorylation in transfected HEK293 cells. Nox4 increased eIF2 phosphorylation in cells transfected with GADD34 and WT PP1, and resulted in even higher phospho-eIF2α levels in cells transfected with N124D or D64N PP1 variants.",
    "ncbi_link": "Nox4: 50507
PP1: 5501
GADD34: 17872"
  },
  {
    "caption": "F. Effect of ascorbate (Asc, 0.5 mM) on phosphatase inhibition in tunicamycin-treated H9c2 cells with overexpression or knockdown of Nox4 (Ad.Nox4 and Ad.shNox4, respectively). In control cells, ascorbate enhanced tunicamycin-stimulated increases in phosphatase activity. Phosphatase activity was lower in Nox4-overexpressing than control cells but was normalized by ascorbate to the same level as in control cells. In Nox4 knockdown cells, tunicamycin-induced increases in phosphatase activity were enhanced and ascorbate had minimal additional effect.",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "A. H9c2 cells treated with tunicamycin (2 µg/ml, 12h) showed significantly lower survival when endogenous Nox4 was silenced (siNox4) as compared to cells treated with a scrambled siRNA (siCtl). Cell survival was restored by treatment with either guanabenz (Gbz, 5 µM) or salubrinal (Sal, 50 µM) but was unaffected by clonidine (Cld, 5 µM). n=3/group.",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "B. Nox4-depleted cells had lower levels of phospho-eIF2α and ATF4 than control cells but these were restored in the presence of guanabenz (Gbz).",
    "ncbi_link": "Nox4: 85431"
  },
  {
    "caption": "D. Hearts from Nox4 knockout (KO) mice and WT controls were subjected to global ischemia followed by aerobic reperfusion (I/R). Infarct size assessed by triphenyltetrazolium chloride (TTC) staining was greater in Nox4 KO hearts compared to WT and was significantly reduced by guanabenz (Gbz). In the representative heart sections shown at the top, white denotes infarct area and red the viable area. Scale bars, 1 mm. Numbers of hearts are indicated within the bars.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "E. Immunoblotting of heart homogenates after I/R showed lower levels of phospho-eIF2a, ATF4 and ER chaperones, and higher levels of cleaved caspase-12, in Nox4 KO compared to WT. Tubulin was used as a loading control. Treatment with guanabenz (Gbz) reversed these changes (blots shown to the right).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "A. Plasma urea levels were elevated to a greater extent in tunicamycin-treated Nox4 KO mice than WT. Co-treatment with guanabenz (Gbz) reduced urea levels in both groups. Numbers of animals are indicated within bars.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "B. 48 hours after systemic tunicamycin treatment, kidneys of Nox4 KO mice showed a marked surface pallor (bottom right).",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "C. TUNEL staining revealed a significantly higher number of apoptotic cells in tunicamycin-treated Nox4 KO mice. n=4/group.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "D. Immunoblotting of kidney homogenates showed significantly elevated cleaved caspase-12 and cleaved PARP levels in tunicamycin-treated Nox4 KO mice compared to WT.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "E. Survival curves showed that a very high proportion of Nox4 KO mice died after AKI. Guanabenz (Gbz) treatment dramatically improved survival in tunicamycin-treated KO mice. Number of animals as indicated. Levels of significance by Kaplan Meier analysis are reported to the right.",
    "ncbi_link": "Nox4: 50490"
  },
  {
    "caption": "Distribution of RT shifts calculated with the -ΔL+ΔE method described in Appendix Figure S1. Different transgenes in a mid-late-replicating region are compared: the IL2R  reporter gene under the control of the βA-globin promoter (βA pro) containing an inactive (i, N=10) or an active origin (ii, N=8) flanked by two copies of FIV( 2xFIV), the blasticidin resistance gene (BsR) under the control of the β-actin promoter (β-act  pro) (iii, N=7) or a combination of these two transgenes (iv, N=8). Blue and black triangles represent reactive loxP sites and recombined inactive loxP sites respectively. Rectangle edges correspond to the 0.25 and 0.75 quartiles, the thick black lines represent the median, the white triangles represent the mean and the whiskers extend to the smallest and largest -ΔL+ΔE values. Statistical analysis was performed with Wilcoxon nonparametric two-tailed tests (ns, not significant; **p<0.01; ***p<0.001).",
    "ncbi_link": "blasticidin resistance gene: 
IL2R: 
β-act: 
BsR: 
β-actin: 
βA: 
βA-globin: "
  },
  {
    "caption": "A. UCSC genome browser visualization of the mid-late insertion site of chromosome 1 (genomic positions: chr1:71,000,000-74,100,000 bp, 3.1 Mb; galGal5). RT  weighted average (WA) values for the wt and the βA-globin+β-actin cell lines are shown. Early-replicated regions (E) are represented in orange and late replicating regions (L) in blue. Annotated genes (Ref Seq genes) are represented below. The mid-late insertion site is indicated with a red arrow and dotted line.",
    "ncbi_link": "β-actin: 
βA-globin: "
  },
  {
    "caption": "B. UCSC genome browser visualization of the mid-late insertion site of chromosome 1 (genomic positions: chr1:72,450,000-72,650,000 bp; 200 kb; galGal5). Tracks of nascent strands (NS) enrichments in the four S phase fractions were represented separately (S1 to S4) for the wt and the 2x(βA-globin+β-actin) cell lines. NS enriched and depleted regions for each fraction are represented in purple and blue respectively. Single reads form SNS aligned and track of replication origins (Ori peaks) determined in (Massip et al, 2019) are reported in between. The three mid-late insertion sites 1, 2 and 3 are indicated with red arrows. Annotated genes and CpG Islands are shown below. Initiation zones  (IZ) and termination zones (TZ) are reported.",
    "ncbi_link": "β-actin: 
βA-globin: "
  },
  {
    "caption": "A. Distribution of -ΔL+ΔE values for clonal cell lines containing one advanced replicon (βA-globin+β-actin) inserted at site 1 (i, N=8) or 3 (iii, N=3) or at both sites on the same chromosome with one GFP  reporter construct composed of the GFP reporter gene under the control of the βA-globin promoter/origin linked to a 1.6 kb fragment of human  chromosome  7 (h.K7) inserted at site 2, either on the same chromosome as 1 and 3 (1+2+3), or on the other chromosome (1+3) (ii, N=5). Blue and black triangles represent reactive loxP sites and recombined inactive loxP sites respectively. Black vertical bars represent insertion sites. Rectangle edges correspond to the 0.25 and 0.75 quartiles, the thick black lines represent the median, the white triangles represent the mean and the whiskers extend to the smallest and largest -ΔL+ΔE  values. Statistical analysis was performed with Wilcoxon nonparametric two-tailed tests (**p<0.01).",
    "ncbi_link": "GFP: 
β-actin: 
βA-globin: "
  },
  {
    "caption": "A. Distribution of -ΔL+ΔE values for clonal cell lines containing one β-actin  construct at site 1 (i, N=7) or at site 1 and 3 (ii, N=5), on the same chromosome. Data information: Blue and black triangles represent reactive loxP sites and recombined inactive loxP sites respectively. Black vertical bars represent insertion sites. Rectangle edges correspond to the 0.25 and 0.75 quartiles, the thick black lines represent the median, the white triangles represent the mean and the whiskers extend to the smallest and largest -ΔL+ΔE values. Statistical analysis was performed with Wilcoxon nonparametric two-tailed tests (**p<0.01).",
    "ncbi_link": "β-actin: 396526"
  },
  {
    "caption": "B. Distribution of -ΔL+ΔE  values for clonal cell lines containing one βA-globin construct at site 1 (i, N=8) or at site 1 and 3 (ii, N=6), on the same chromosome. Data information: Blue and black triangles represent reactive loxP sites and recombined inactive loxP sites respectively. Black vertical bars represent insertion sites. Rectangle edges correspond to the 0.25 and 0.75 quartiles, the thick black lines represent the median, the white triangles represent the mean and the whiskers extend to the smallest and largest -ΔL+ΔE  values. Statistical analysis was performed with Wilcoxon nonparametric two-tailed tests (**p<0.01).",
    "ncbi_link": "βA-globin: "
  },
  {
    "caption": "C. After 1, 8, 24 and 48 h of 4-hydroxytamoxifen treatment, genomic DNA was extracted and quantified by semi-quantitative PCR (see Appendix Figure S6). Error bars correspond to the standard deviation for PCR duplicates. The percentages of cells with the large 1+3 and loxP_LE (1) + βA-globin+β-actin (3) or β-actin (1+3) excision at each time point are shown for different cell lines.",
    "ncbi_link": "β-actin: 
βA-globin: "
  },
  {
    "caption": "A, B. Clones 1+2+3, 1+3 (A) and loxP_LE (1) + βA-globin+β-actin (3) (B) were used to assess chromatin accessibility  within the transgenes. The positions of the amplicons used for quantification in each shifting construct individually (thick black lines; 5' 2xFIV-1 or -3,   β-actin pro-1 or -3, BsR gene, PuroR gene, LoxP site), in both shifting constructs (βA  pro 1 and 2, IL2R gene, 3' 2xFIV1-3) or in the GFP reporter construct (βA-GFP, GFP gene, h.K7) are shown. The insertion sites on the wt chromosome  (insertion sites 1, 2 and 3) and a genomic region located 5 kb downstream from the insertion site (insertion site +5kb) were used as controls for the targeted genomic region. The endogenous active MED14  promoter was analyzed as a control. Blue and black triangles represent reactive loxP sites and recombined inactive loxP sites respectively. Black vertical bars represent insertion sites. Quantifications by  real-time qPCR  of total chromatin  (input) extracted from two 1+2+3, 1+3 and loxP_LE (1)+ βA-globin+β-actin (3) clonal cell lines, after digestion with micrococcal nuclease (MNAse, 2.5 U, 10 U, 40 U, 160 U/mL) and size selection were shown. Error bars indicate the standard deviation for qPCR triplicates, for two independent clones. Data are presented as total chromatin  input relative to the condensed  genomic regions (cond1 and cond2) used for the normalization. ",
    "ncbi_link": "MED14: 
β-actin: 
BsR: 
GFP: 
IL2R: 
PuroR: 
βA-globin: "
  },
  {
    "caption": "A, B. RT profiles of chromosomal  alleles following the targeted integration of a βA-globin+β-actin  construct into two late-replicating loci, 1 (A) and 2 (B) in two or three clonal cell lines respectively. Nascent strands (NS) were quantified by  real-time qPCR in four S phase fractions. Specific primer pairs determine the  RT profile for the modified allele (With), the wt allele (Without) and both alleles (Both). The endogenous β-globin locus was analyzed as an early-replicated control. The modified (Mod) and wild-type (wt) alleles are shown. Difference -ΔL+ΔE values calculated at the target site following transgene integration are indicated (see Appendix Figure S1). Error bars correspond to the standard deviation for qPCR  duplicates. The black vertical bars represent the precise insertion position.",
    "ncbi_link": "β-actin: 
β-globin: 
βA-globin: "
  },
  {
    "caption": " A. Arabidopsis root expressing the dual reporter TCSn::dndT-tNOS DR5v2:3nGFP that is sensitive to cytokinin (CK) and auxin. CK (red), auxin (green) and overlay of both signals detected in nuclei of cells at the root tip (top, scale bar 50 µm). Green, pink, and blue arrowheads point at epidermal cells located in the meristematic (MZ), transition (TZ) and elongation (EZ) zones, respectively. Magnification of the TZ shown (bottom, scale bar 10 µm). ",
    "ncbi_link": "dndT: 
DR5: 
GFP: 
tNOS: "
  },
  {
    "caption": " B. Relative fluorescence intensity of TCSn::ntdT:tNOS signal (red) and DR5v2:3nGFP signal (green) measured in epidermal cells along the longitudinal root growth axis. Cell number 1 corresponds to a meristematic cell placed at position -4 before the beginning of TZ (as marked by green arrow at 2A). Mean ± s.d., * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 by Student's t-test, n= 18 roots. ",
    "ncbi_link": "DR5: 
GFP: 
ntdT: 
tNOS: "
  },
  {
    "caption": " A-D. CMTs visualized with MAP4-GFP in root epidermal cells of the cre1-12 mutant at the transition (TZ) and the elongation (EZ) zones at time point 0 and 60 min after mock (DMSO) (A), cytokinin (CK) (B), auxin (C) and CK plus auxin (D) treatments. As CK and auxin sources 10 µM BAP and 0.1 µM NAA were used, respectively. For the double CK plus auxin treatment roots were pretreated for 60 min with CK, whereafter they were transferred to medium supplemented with both compounds. Scale bar 10 µm. ",
    "ncbi_link": "cre: 833552"
  },
  {
    "caption": " F, G. Analysis of the CMT plus-end growth with the EB1b-GFP reporter in cre1-12. F. Z-stack maximum image projection of EB1b-GFP tracked for 30 seconds (on the left) and single trajectories of EB1b-GFP signal tracked over 60 sec (on the right) in root epidermal cells of the EZ in the wild type and cre1-12 treated with CK for 60 min. Scale bars 10 µm and 0.5 µm, respectively. G. CMT plus-end growth rates (µm/min) quantified from the EB1b-GFP trajectories tracked during 5 min in epidermal cells of the EZ treated with mock (DMSO) or CK. In the boxplots, the center lines show the medians; box limits indicate the 25th and 75th percentiles as determined by the Graphpad software; whiskers span minimum to maximum values, individual data points are represented by dots. (ns = non-significant, *** P < 0.001 by Student's t-test, n= 7-9 cells with 7 roots per condition in 3 independent experiments). Concentrations and treatment conditions (F, G) were as for (A, B). ",
    "ncbi_link": "GFP: 
cre: 833552"
  },
  {
    "caption": " H, I. CMTs visualized with MAP4-GFP in root epidermal cells of the cre1-12 mutant. Cells at the TZ, the EZ and the DZ were monitored at time point 0 and 60 min after treatment with oryzalin (1 µM) (H), and CK plus oryzalin (I). As CK source 10 µM BAP was used and 1 µM oryzalin. For double (CK and oryzalin) treatment roots were pretreated for 60 min with CK and then transferred to medium supplemented with both compounds. Scale bar 10 µm. J. Quantification of the MAP4-GFP CMTs reporter signal in cre1-12 root epidermal cells at different root zones treated with mock (DMSO, white box), oryzalin (1 µM, light grey box) and CK (10 µM BAP) plus oryzalin (1 µM) (dark grey box). For double treatments, roots pretreated for 60 min with CK prior to transfer to medium supplemented with both compounds. Boxplots represent ratio between mean fluorescence intensity (arbitrary units) measured in epidermal cells at 60 and 0 min. The center lines show the medians and the box limits indicate the 25th and 75th percentiles; whiskers span the minimal to maximal values, individual data points are represented by dots. Ratio close to 1 (segmented line) corresponds to the unchanged MAP-GFP signal for 60 min. (* P < 0.05, **** P < 0.0001 by Student's t-test, n= 3-10 cells per root growth zone with 5-8 roots per condition in 4 independent replicates). ",
    "ncbi_link": "cre: 833552"
  },
  {
    "caption": " A. Relative root growth of wild-type (Col-0) (grey lines) and 35S::ARR1∆DDK-GR (purple lines) seedlings grown on mock (DMSO; continuous line) or with dexamethasone (DEX 10 µM; dashed line) supplemented medium. Five days old seedlings (Day 0) were monitored for 3 days. Mean ± s.d.; ** P < 0.01, **** P < 0.0001 by Student's t-test, referred to wild-type - mock. n = 12-14 roots. ",
    "ncbi_link": "ARR1: 820940"
  },
  {
    "caption": " B. Immunostaining of α-tubulin in epidermal cells of the transition (TZ) and the elongation (EZ) zone of 35S::ARR1∆DDK-GR roots after non-, 3h or 16h of treatment with dexamethasone (DEX 10 µM). Scale bar 10 µm. ",
    "ncbi_link": "ARR1: 820940"
  },
  {
    "caption": " D, E. Analysis of root sensitivity to oryzalin in wild-type (Col-0) and 35S::ARR1∆DDK-GR. Seedlings were grown for 5 days on mock (Murashige and Skoog) medium and then transferred to medium supplemented with 1 µM oryzalin, CK with oryzalin (10 µM BAP and 1 µM oryzalin), with or without DEX 10 µM, for 3 days. For the double CK and oryzalin treatment, seedlings were pretreated with 10 µM BAP for 60 min prior to transfer to medium supplemented with both compounds. Representative images; white arrowheads indicate root length at day of transfer. Scale bar 1 mm (D). Quantifications calculated as percentage (%) of root tips exhibiting swelling (dark grey bars), and weak and strong resistance to oryzalin (grey and white bars, respectively). On the right representative images of root phenotype categories. n=10-25 roots per treatment were evaluated. (E). ",
    "ncbi_link": "ARR1: 820940"
  },
  {
    "caption": " F. Relative root growth of wild-type (Col-0) (grey lines) and 35S::ARR1∆DDK-GR (purple lines) seedlings grown on oryzalin 1µM (continuous line) or on oryzalin 1µM and DEX 10 µM (dashed line) supplemented media monitored for 3 days. Day 0, day of transfer. Mean ± s.d.; n = 12-14 roots. ",
    "ncbi_link": "ARR1: 820940"
  },
  {
    "caption": " A. Time lapse imaging of Arabidopsis root expressing the plasma membrane marker (PM) pUB10::EYFP-NPSN12 (wave line W131Y)(Geldner et al, 2009). Root growth recorded for 2 min and overlay of root tip images at time point 0 (magenta) and 2 min (cyan) used for the calculation of the root growth rate (RGR) and the cell elongation rate (CER). Scale bar 25 µm. B. RGR of wild type (grey bars) and cre1-12 (blue bars) treated for 1 and 4 hours with mock (DMSO), CK (10 µM BAP) or auxin (0.1 µM NAA). Mean ± s.d., (* P < 0.05and **** P < 0.0001 by the Student's t-test, n= 5-8 roots per condition in 3 independent replicates). ",
    "ncbi_link": "cre: 833552"
  },
  {
    "caption": " C-E. Analysis of CK and auxin effects on CER of epidermal cells. Epidermal cells of the TZ and the EZ in the wild type and cre1-12 with PMs visualized with the YFP-NPSN12 marker. Overlay of images of epidermal cells at time 0 (magenta) and 2 min (cyan) is presented. Scale bar 10 µm (C). CER (µm/min) of root epidermal cells of the TZ (D) and the EZ (E) of the wild type (grey bars) and cre1-12 (blue bars) mutant. Hormone concentrations and conditions of treatment (D, E) were as described for (C). Mean ± s.d., (* P < 0.05, ** P < 0.01, *** P < 0.001 and **** P < 0.0001 by Student's t-test, n=15-20 cells per root growth zone in 3-6 roots per condition, in 3 independent). ",
    "ncbi_link": "cre: 833552"
  },
  {
    "caption": "(G) Representative images showing the effects of a knockdown of the endogenous Spindly  in HeLa  cells. RNAi treatment was performed for 48 h with 50 nM siRNA. Before fixation, cells were synchronized in  G2 phase with 9 μM RO3306  for 16 h and then released into mitosis. Subsequently, cells were immediately treated with 3.3 μM nocodazole  for an additional hour. CREST  serum  was used to visualize kinetochores  and DAPI  to stain  DNA. Scale bar: 10 µm. Three biological replicates were performed.",
    "ncbi_link": "Spindly: 54908"
  },
  {
    "caption": "(I) Levels of CENP-E and Zwilch  were assessed in control cells and in cells treated as in panel G to knockdown Spindly. Three biological replicates were performed. (J) Scatter dot plots representing normalized total area of the CENP-E and Zwilch  signals, normalized to the RNAi negative control, in the indicated number of cells from the experiment shown in panel I. Red lines indicate mean and standard deviation. Statistical analysis was performed with a nonparametric t-test comparing two unpaired groups (Mann-Whitney test). Symbols indicate: n.s. = p > 0.05, ∗ = p ≤ 0.05, ∗∗ = p ≤ 0.01, ∗∗∗ = p ≤ 0.001, ∗∗∗∗ = p ≤ 0.000.",
    "ncbi_link": "Spindly: 54908"
  },
  {
    "caption": "(D) Representative images of fixed HeLa  cells electroporated  with full-length mChSpindly and mChSpindly354-605 constructs in cells depleted of endogenous Spindly  by RNAi. Spindly localization  was detected with an antibody against the C-terminal region of Spindly. Corona   expansion or lack thereof were monitored through CENP-E. CREST serum was used to visualize kinetochores, DAPI  to stain  for DNA. Scale bar: 10 µm. Experiments were replicated three times.",
    "ncbi_link": "Spindly: 54908"
  },
  {
    "caption": "A, B. Representative images of H&E- (A) and PAS- (B) stained colon sections from wild-type and Angptl2-/- mice. Scale bar = 100μm.C, D. Representative images of colon crypts as assessed by Ki-67 (C) and pH3 (D) staining. Scale bar = 100 μm.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "E. mRNA levels of indicated proliferation and ISC markers in isolated crypts from wild-type (n=4) and Angptl2-/- (n=4) mice based on qRT-PCR analysis.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "F. Western blotting analysis of isolated colon crypts from wild-type and Angptl2-/- mice. HSC70 served as an internal control. Numbers below panels represent normalized expression of proteins.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "G. IHC for expression of active β-catenin in colon or wild-type and Angptl2-/- mice. Scale bar = 50 μm.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "A. Survival rates of wild-type (n=33) and Angptl2-/- (n=33) mice supplied with drinking water containing 2.5 % DSS for 6 days and then untreated water for 6 more days, from two different experiments. ***p < 0.001, by log-rank test.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "B. Representative images of colons from wild-type and Angptl2-/- mice following DSS treatment for 6 days and then untreated water for 6 more days (at days 12).C. Colon length of wild-type (n=7) and Angptl2-/- (n=6) mice following DSS treatment for 6 days and then untreated water for 6 more days (at days 12).",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "D, E, F. Representative images of colon crypts as assessed by H&E (D), Ki-67 (E), and pH3 (F) staining in wild-type and Angptl2-/- mice following DSS treatment for 6 days and then untreated water for 6 more days (at days 12). Scale bar = 100 μm.G, H. The number of regenerating crypts as quantified using Ki-67 (G) and pH3 (H) staining. Each data point represents the number of Ki-67-positive viable crypts or the number of pH3-positive cells in a single field of view. Multiple areas in at least 6 mice per genotype were quantified. Numbers below panels represent the average.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "I. IHC for expression of active β-catenin in colon or wild-type and Angptl2-/- mice following DSS treatment for 6 days and then untreated water for 6 more days (at days 12). Scale bar = 50 μm.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "J. mRNA levels of indicated genes in isolated crypts from wild-type (n=4) and Angptl2-/-(n=4) mice following DSS treatment for 6 days and then untreated water for 6 more days (at days 12).",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "A. Weight loss of wild-type (n=4) and Angptl2-/- (n=5) mice in days following 12 Gy irradiation.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "B. Small intestine and colon length from wild-type (n=4) and Angptl2-/- (n=5) mice 5 days after 12 Gy irradiation.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "C, D. Representative images of crypts of small intestine as assessed by H&E (C) and Ki-67 (D) staining in wild-type and Angptl2-/- mice 5 days after 12 Gy irradiation. Scale bar = 100 μm.E. The number of regenerating crypts in small intestine as quantified by Ki-67 (D) staining at days 3 and 5. Each data point represents the number of Ki-67-positive viable crypts in a single field of view. Multiple areas in at least 3 mice per genotype were quantified. Numbers below panels represent average.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "F, G. Representative images of colon crypts as assessed by H&E (F) or Ki-67 (G) staining in wild-type and Angptl2-/- mice 5 days after 12 Gy irradiation. Scale bar = 100 μm.H. The number of regenerating colon crypts as quantified by using Ki-67 (G) staining at days 3 and 5. Each data point represents the number of Ki-67-positive viable crypts in a single field of view. Multiple areas in at least 3 mice per genotype were quantified. Numbers below panels represent average.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "A. Angptl2 mRNA levels in small intestine (proximal, mid and distal), cecum and colon (proximal and distal) of wild-type mice based on qRT-PCR analysis. n=5.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "B. ANGPTL2 IHC in colon from wild-type and Angptl2-/- mice. The Angptl2-/- colon image serves as a negative control. Scale bar = 50 μm.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "A, B, C. mRNA levels of indicated genes in ISEMFs from wild-type (n=4) and Angptl2-/- (n=3) mice based qRT-PCR analysis.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "D. Representative staining for P-Smad1/5 in crypts from wild-type and Angptl2-/- mice following DSS treatment for 6 days and then untreated water for 6 more days (DSS) or untreated water for 12 days (Untreated). Dashed lines indicate half of the crypt and arrowheads show P-Smad1/5-positive cells in lower halves of crypts. Scale bar = 50 μm.E. The number of P-Smad1/5-positive cells in the crypt base (n=60) from wild-type and Angptl2-/- mice following DSS treatment for 6 days and then untreated water for 6 more days (DSS) or untreated water for 12 days (Untreated). Multiple areas in 3 mice per genotype were quantified.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "F. Western blotting analysis of isolated colon crypts from wild-type and Angptl2-/- mice. HSC70 serves as an internal control. Numbers below panels represent normalized protein expression.",
    "ncbi_link": "Angptl2: 26360"
  },
  {
    "caption": "A. mRNA levels of indicated genes in colon and cultured ISEMFs from wild-type mice (n=4) based on qRT-PCR analysis. Inta5, Integrin α5; Intb1, Integrin β1.",
    "ncbi_link": "Inta5: 16402
Integrin α5: 16402
Intb1: 16412
Integrin β1: 16412"
  },
  {
    "caption": "C, D. mRNA levels of Bmp2 and Bmp7 in ISEMFs from wild-type mice 24 h after treatment with integrinα5β1 antibody or various signaling pathway inhibitors. n=3. U0126, ERK inhibitor; LY294002, PI3K inhibitor; BAY11-7085, NF-κB inhibitor.",
    "ncbi_link": "Bmp2: 12156
Bmp7: 12162"
  },
  {
    "caption": "Survival rates of control and Cdc50a cKO mice after oil or 4-OHT injection (n = 5 for each group, P*** = 0.0003).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Bar graphs showing audiogenic seizure scores following auditory stimuli (5, 10, 15, 20, 40 kHz or white noise (WN) at 70, 80, 90, or 100 dB) in control (E) and Cdc50a cKO (F) mice (n = 8 for each group).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Representative confocal z-stack images showing cFos (magenta)-positive neurons from control and Cdc50a cKO mice (CTX: cortex, HP: hippocampus, and IC: inferior colliculus). Scale bar, 20 μm. Bar graphs showing the relative area of cFos-positive cells in the brains of control and Cdc50a cKO mice (n = 5 for each group, **P = 0.0030, n.s., not significant).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Schematic diagram of the experiment. Representative confocal z-stack images of PSD95 (green)- and VGLUT1 (red)-positive excitatory (A) and Gephyrin (green)- and VGAT (magenta)-positive inhibitory (B) synapses in the CTX, HP, and IC (CTX: cortex, HP: hippocampus, and IC: inferior colliculus) of control and Cdc50a cKO mice. The dashed line represents where the high magnified insert was taken from. Scale bar, 20 μm.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Representative current clamp traces from the IC of control and Cdc50a cKO mice; +100 pA (upper) and +400 pA (lower) currents were injected into control mice (left) and Cdc50a cKO mice (right) for 500 ms.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "The bar graphs show the relative percentages of neurons showing PS exposure only in the soma (left) and overall PS exposure (right) (n = 30-40 cells for each group) in control and Cdc50a cKO mice.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Schematic diagram of imaging of the neuronal somas and proximal and distal dendrites of neurons in the CA1 region of the HP. Representative confocal z-stack images showing Gephyrin-positive inhibitory post-synapses in the somas (red) and proximal (green) and distal dendrites (cyan) of neurons in the CA1 region of the HP in control and Cdc50a cKO mice. Scale bar, 20 μm. Bar graphs showing the number of Gephyrin-positive inhibitory post-synapses in the somas and proximal and distal dendrites of neurons in the CA1 of the HP in control and Cdc50a cKO mice (n = 4 for each group, P*** = 0.0002, P**** < 0.0001).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Representative confocal z-stack and colocalization images of Gephyrin (green), IBA1 (blue), and CD68 (red) in the IC of control and Cdc50a cKO mice. Scale bar, 20 μm. Bar graphs showing the relative colocalization area of Gephyrin and CD68 in the IC of control and Cdc50a cKO mice (n = 3 for each group, **P = 0.0024).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Representative confocal z-stack images of microglia (IBA1, green, upper) and inhibitory synapses (Gephyrin: green, VGAT: red, lower) in the IC of control;DMSO, control;PLX3397, Cdc50a cKO;DMSO and Cdc50a cKO;PLX3397 mice. The dashed line represents where the high magnified insert was taken from. Scale bar, 20 μm. Bar graphs showing the relative area of IBA1-positive cells in the IC of control;DMSO, control;PLX3397, Cdc50a cKO;DMSO and Cdc50a cKO;PLX3397 mice (n = 3 for each group, control;DMSO versus control;PLX3397, *P = 0.0428, control;DMSO versus Cdc50a cKO;DMSO, ***P = 0.0002, Cdc50a cKO;DMSO versus Cdc50a cKO;PLX3397, ***P = 0.0005). Bar graphs showing the number of inhibitory (Gephyrin- and VGAT-positive) synapses in the IC of control;DMSO, control;PLX3397, Cdc50a cKO;DMSO and Cdc50a cKO;PLX3397 mice (n = 3 for each group, P**** < 0.0001).",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "Representative confocal z-stack images of Gephyrin (green)- and VGAT (red)-positive inhibitory synapses in the IC (inferior colliculus) of control;C3+/+, control;C3-/-, Cdc50a cKO;C3+/+ and Cdc50a cKO;C3-/- mice. The dashed line represents where the high magnified insert was taken from. Scale bar, 10 μm.",
    "ncbi_link": "C3: 12266
Cdc50a: 69981"
  },
  {
    "caption": "Representative confocal z-stack images of Gephyrin (green)- and VGAT (red)-positive inhibitory synapses in the IC of control;Mertk+/+, control;Mertk-/-, Cdc50a cKO;Mertk+/+ and Cdc50a cKO;Mertk-/- mice. The dashed line represents where the high magnified insert was taken from. Scale bar, 20 μm.",
    "ncbi_link": "Mertk: 17289
Cdc50a: 69981"
  },
  {
    "caption": "Schematic diagram of the experiment in which PS exposure was measured in the brains of 1-month- and 3-month-old wild-type mice by injecting AAV9-GFAP-secA5-mCherry in the neonatal stage (P0). Representative confocal z-stack colocalization images of Gephyrin (green), VGAT (blue), and secA5 (red) in the HP (hippocampus) of 1-month- and 3-month-old wild-type mice. The white circles indicate secA5-positive inhibitory synapses. Scale bar, 10 μm. Bar graphs showing the expression of secA5 (B) and IBA1 (C) in inhibitory post-synapses (Gephyrin-positive, green) and pre-synapses (VGAT-positive, blue) in the HP of 1-month- and 3-month-old wild-type mice (n = 4 for each group, ***P = 0.0009, *P = 0.0248, n.s., not significant).",
    "ncbi_link": "GFAP: 
mCherry: 
secA5: 11747"
  },
  {
    "caption": "Schematic diagram of the experiment in which microglial Mertk KO (CX3CR1-CreERT2;Mertkfl/fl) and control (Mertkfl/fl) mice were generated. Both 1-month-old microglial Mertk KO mice and 1-month-old control mice were injected with 4-OHT for 5 consecutive days. Representative confocal z-stack images of Gephyrin (green)- and VGAT (magenta)-positive inhibitory synapses in the HP of Mertkfl/fl and CX3CR1-CreERT2;Mertkfl/fl mice. The white circles indicate inhibitory synapses. Scale bar, 10 μm. Bar graphs showing the number of inhibitory (Gephyrin- and VGAT-positive) synapses in the HP of Mertkfl/fl and CX3CR1-CreERT2;Mertkfl/fl mice (n = 4 for each group, **P = 0.0027, *P = 0.0062). Representative confocal z-stack colocalization images of Gephyrin (green), VGAT (blue) and secA5 (red) in the HP of Mertkfl/fl and CX3CR1-CreERT2;Mertkfl/fl mice. The white circles indicate secA5-positive inhibitory synapses. Scale bar, 10 μm. Bar graphs showing the relative expression of secA5 in inhibitory synapses in the HP of Mertkfl/fl and CX3CR1-CreERT2;Mertkfl/fl mice (n = 4 for each group, *P = 0.0015).",
    "ncbi_link": "Cre: 2777477
CX3CR1: 13051
ERT2: 13982
Mertk: 17289"
  },
  {
    "caption": "Body weights of WT and Rcan1-KO mice fed normal chow diet (NC) for 20 weeks starting at 8-10 weeks of age (male, n=15 each). Data information: values shown are mean ±SD * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (two-way ANOVA with multiple comparisons, except for A and B, which used multiple t-tests).",
    "ncbi_link": "Rcan1: 54720"
  },
  {
    "caption": "Body weights of WT and Rcan1-KO mice fed a high-fat diet (HFD) for 20 weeks starting at 8-10 weeks of age (male, n=15 each). Data information: values shown are mean ±SD * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (two-way ANOVA with multiple comparisons, except for A and B, which used multiple t-tests).",
    "ncbi_link": "Rcan1: 54720"
  },
  {
    "caption": "Cholesterol remaining in the feces of WT and Rcan1-KO mice fed a HFD, measured as mMol per mg of feces (males, n=4 over 3 days). Cholesterol content of NC and the HFD chow (input) were measured for comparison. Data information: values shown are mean ±SD * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (two-way ANOVA with multiple comparisons, except for A and B, which used multiple t-tests).",
    "ncbi_link": "Rcan1: 54720"
  },
  {
    "caption": "triglyceride remaining in the feces of WT and Rcan1-KO mice fed a HFD, measured as mMol per mg of feces (males, n=4 over 3 days). triglyceride content of NC and the HFD chow (input) were measured for comparison. Data information: values shown are mean ±SD * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (two-way ANOVA with multiple comparisons, except for A and B, which used multiple t-tests).",
    "ncbi_link": "Rcan1: 54720"
  },
  {
    "caption": "L Transcript levels for inflammatory markers Monocyte chemoattractant protein-1 (Mcp-1), macrophage antigen F4/80 (F480), tumor necrosis factor-alpha (Tnfα), and tumor necrosis factor-beta (Tnfβ) in gWAT of WT and KO after 25 weeks on NC or HFD (males, n=4-5). Transcript levels were normalized to 18S Data information: values shown are mean ±SD * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (two-way ANOVA with multiple comparisons, except for A and B, which used multiple t-tests).",
    "ncbi_link": "F480: 13733
macrophage antigen F4/80 : 13733
Mcp-1: 20296
Monocyte chemoattractant protein-1: 20296
Tnfβ: 16992
tumor necrosis factor-beta: 16992
tumor necrosis factor-alpha: 21926"
  },
  {
    "caption": "C Transcript levels for genes involved in lipid metabolism and gluconeogenesis in livers of WT and KO mice after 25 weeks on NC or HFD. Stearoyl-Coenzyme A desaturase (Scd1), fatty acid transporter (CD36), glycerol-3-phosphate acyltransferase (Gpat), carnitine palmitoyltransferase I (Cpt1), peroxisome proliferator-activated gamma (PPARγ), pyruvate dehydrogenase acetyl-transferase (Pdk4), PPARγ coactivator 1 alpha (PGC1α), diacylglycerol O-acyltransferase (Dgat), and facilitated glucose transporter (Glut4). (males, n=4-5). Transcript levels were normalized to 18S. Data information: values shown are mean ±SD. * = p < 0.05; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001 (two-way ANOVA with multiple comparisons).",
    "ncbi_link": "18S: 
CD36: 12491
fatty acid transporter: 12491
carnitine palmitoyltransferase I: 12895///12894
Cpt1: 12895///12894
Dgat: 13350
diacylglycerol O-acyltransferase: 13350
glycerol-3-phosphate acyltransferase: 14732
Gpat: 14732
Pdk4: 27273
pyruvate dehydrogenase acetyl-transferase: 27273
peroxisome proliferator-activated gamma: 19016
PPARγ: 19016
PGC1α: 19017
PPARγ coactivator 1 alpha: 19017
Scd1: 20249
Stearoyl-Coenzyme A desaturase: 20249
glucose transporter: 20528
Glut4: 20528"
  },
  {
    "caption": "Transcript levels for Rcan1.1 and Rcan1.4 during differentiation of 3T3-L1 adipocytes, measured at 0, 1, 2, 3, 4, 6 and 24 hours following the addition MDI as well as at 3, 7 and 10 days as indicated (n=3). * = p < 0.05; ** = p < 0.01, student's t-test, unpaired, vs 0 time point. Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD",
    "ncbi_link": "18S: 
Rcan1.1: 54720
Rcan1.4: 54720"
  },
  {
    "caption": "B Western blot for RCAN1.1, RCAN1.4 and tubulin (TUB) in whole cell extracts of 3T3-L1 adipocytes transfected with a control si-RNA or ones targeting either Rcan1.4 or Rcan1.1 (20 μg per lane).",
    "ncbi_link": "Rcan1.1: 54720
Rcan1.4: 54720"
  },
  {
    "caption": "E Transcript levels for Pgc1-α, in 3T3-L1 adipocytes transfected with the indicated si-RNAs and assayed over 10-days of differentiation (n=3). Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD",
    "ncbi_link": "18S: 
Pgc1-α: 19017"
  },
  {
    "caption": "G Transcript levels for Adrenoceptor beta 3 (Adrb3), uncoupling protein 1 (Ucp1), PPARγ coactivator 1 alpha (PGC1α), and deiodinase type II (Dio2) Ing-svf cultures transfected with control siRNA (C) or one targeting Rcan1 (KD) then maintained in growth media (G), or differentiated for ten-days (D) with and without the addition of 100 mM isoproterionol for 6 hours prior to harvesting (D+ISO) (n=2 in triplicate). * = p < 0.05; ** = p < 0.01, two-way ANOVA with multiple comparisons. Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD",
    "ncbi_link": "18S: 
Adrb3: 11556
Adrenoceptor beta 3: 11556
deiodinase type II: 13371
Dio2: 13371
PGC1α: 19017
PPARγ coactivator 1 alpha: 19017
Rcan1: 54720
Ucp1: 22227
uncoupling protein 1: 22227"
  },
  {
    "caption": "H, I Transcript levels for the indicated panel of genes relevant to adipocyte differentiation in Platelet-derived growth factor receptor alpha-positive (PDGFRα+) and lineage-negative (Lin-) stromal vascular cells isolated by FACS sorting from sWAT of WT (black bars) and KO (red bars). In H, isolated cells were maintained in growth media. In I, cultures were treated with MDI then differentiated for 10 days. * = p < 0.05; ** = p < 0.01, student's t-test, unpaired, WT vs. KO. Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD",
    "ncbi_link": "18S: 
PDGFRα: 18590
Platelet-derived growth factor receptor alpha: 18595"
  },
  {
    "caption": "Transcript levels of Pgc1α and Ucp1 in sWAT of male and female WT and KO mice after 24 hours at RT or 4°C (n= Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD. * = p < 0.05; ** = p < 0.01. (two-way ANOVA with multiple comparisons",
    "ncbi_link": "18S: 
Pgc1α: 19017
Ucp1: 22227"
  },
  {
    "caption": "C Transcript levels of Ucp1, Pgc1α, Adrb3, retinoblastoma 1 (Rb1), zinc finger protein 423 (Zfp423), and PR domain containing 16 (Prdm16) were quantified in sWAT of WT and KO mice after 25 weeks on a HFD (n=4-5). Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD. * = p < 0.05; ** = p < 0.01. ; unpaired student's t-test",
    "ncbi_link": "18S: 
Adrb3: 11556
Pgc1α: 19017
PR domain containing 16: 70673
Prdm16: 70673
Rb1: 19645
retinoblastoma 1: 19645
Ucp1: 22227
Zfp423: 94187
zinc finger protein 423: 94187"
  },
  {
    "caption": "D Transcript levels of Pgc1α-1b and Pgc1α-1a isoforms in sWAT of WT and KO 8 week old females maintained at 24°C (RT) or housed at 4°C for 24 hours (n=5). Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD. * = p < 0.05; ** = p < 0.01. (two-way ANOVA with multiple comparisons",
    "ncbi_link": "18S: 
Pgc1α-1a: 19017
Pgc1α-1b: 19017"
  },
  {
    "caption": "E. Western blot for RCAN1 in various skeletal muscle groups. Each lane was loaded with 20 μg of total protein from plantaris (PL), soleus (SOL), extensor digitorum longus (EDL), tibialis anterior (TA), red gastrocnemius (RG), white gastrocnemius (WG), white vastus lateralis (WV), heart ventricle (HT), atria, diaphragm (Dia), and Tong. The lane containing brain extract was loaded with 10 μg of protein. Antibody specificity was validated by running 20 μg of protein from the heart of an Rcan1-KO animal (HT-KO). The asterisks * indicate the location of putative proteolytic fragments of RCAN1.1.",
    "ncbi_link": "Rcan1: 54720"
  },
  {
    "caption": "F Transcript levels of Sln in skeletal muscle (tibialis anterior) of 8-10 week old WT and KO mice housed at RT. (n=4-5 each gender). G Transcript levels of Sln in skeletal muscle (tibialis anterior ) of 8-10 week old male WT and KO animals housed at RT. (n=5).Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD. * = p < 0.05; ** = p < 0.01. (two-way ANOVA with multiple comparisons F, ; unpaired student's t-test in G.",
    "ncbi_link": "18S: 
Sln: 66402"
  },
  {
    "caption": "J Activity of the Sln-Luc reporter in C2C12 myoblasts transiently transfected with an empty control vector or ones expressing constitutively active calcineurin (CnA*) and Rcan1. Luciferase activity was normalized to beta-galactosidase activity from a co-transfected vector. (n=3, assayed in duplicate). Data information: Transcript levels were normalized to 18S. All values shown are mean ±SD. * = p < 0.05; ** = p < 0.01. (two-way ANOVA with multiple comparisons",
    "ncbi_link": "18S: 
beta-galactosidase: 
Luc: 
Luciferase: 
calcineurin: 19055
CnA: 19055
Rcan1: 54720
Sln: 66402"
  },
  {
    "caption": "B, C Correlation of Rcan1 expression in gonadal adipose and liver with body weight, plasma insulin and plasma triglycerides, in a data set comparing backgrounds susceptible (BTBR background) or resistant (C57BL/6 background) to diabetes when carrying the leptinob/ob (ob) mutation. Measures are reported as the ratio of the mean log10 intensity (ml ratio). Regression line (black), r = linear regression, p = p-value.",
    "ncbi_link": "leptin: 16846"
  },
  {
    "caption": "(C-D) RNA-Seq data from GTEx of the normalized expression of human CSAG1 (C) and CSAG2 (D) in the indicated tissues. Number of biological replicates are as follows: testis 361, brain 255, small intestine 187, white adipose 663, muscle 803, skin 604, esophagus 555, stomach 359, liver 226, heart 429. blood vessel 663, lung 578, colon 373, nerve 619, pituitary 283, blood 755, adrenal gland 258, kidney 85, prostate 245, salivary gland 162, ovary 180, breast 459, pancreas 328, vagina 156, uterus 142, spleen 241, fallopian tube 9, bladder 21, cervix 10. Central band indicates median, boxes define 25 and 75 percentiles, and whiskers define 5 and 95 percentiles.",
    "ncbi_link": "CSAG1: 158511
CSAG2: 102723547"
  },
  {
    "caption": "(E-F) Expression of CSAG1 (E) and CSAG2 (F) in normal adjacent (blue) or tumor tissue (red) from TCGA RNA-Seq data. N.D. represents normal adjacent is not available. Data visualized by firebrowse. Number of biological replicates are as follows: ACC 41, BLCA 307, BRCA 524, CESC 175, CHOL 11, COAD 153, COADREAD 232, DLBC 36, ESCA 121, HNSC 416, KICH 46, KIPAN 515, KIRC 411, KIRP 58, LAML 7, LGG 528, LUAD 301, LUSC 400, MESO 31, OV 183, PCPG 70, PRAD 204, READ 79, SARC 156, SKCM 422, STAD 288, STES 409, TGCT 126, THCA 408, THYM 75, UCEC 306, and UCS 37. Central band indicates median, boxes define 25 and 75 percentiles, and whiskers define 5 and 95 percentiles.",
    "ncbi_link": "CSAG1: 158511
CSAG2: 102723547"
  },
  {
    "caption": "(H-K) Expression of CSAG1 (H-I) or CSAG2 (J-K) in patients from indicated cancer types correlates with poor overall survival. Data is from TCGA and visualized by kmplotter.",
    "ncbi_link": "CSAG1: 158511
CSAG2: 102723547"
  },
  {
    "caption": "(A-B) The effect of stable knockdown CSAG2 in HCT116 (A) or A375 (B) were assayed for clonogenic growth on plastic for 7 days. The number of colonies was quantified and is shown. Data are represented as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(C-D) The effect of stable knockdown CSAG2 in HCT116 (C) or A375 (D) were determined for anchorage-independent growth in soft agar colony formation assays for 14 days. The number of colonies was quantified and is shown. Data are represented as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(E-F) Knockdown of CSAG2 in A375 (F) or HCT116 (E) cells decreases xenograft tumor growth in mice. Cells with doxycycline-inducible shRNAs were implanted into NOD SCID gamma mice. Doxycycline (2 mg/mL) was administered via drinking water. Tumor growth was monitored over time. Data are represented as the mean ± SD, n=6 mice for each group.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(G-H) Stable expression of CSAG2 in HCT116 (G) and CSAG2-negative H460 (H) cells increases anchorage-independent growth in soft agar colony formation assays, n=3 biological replicates. Data are represented as the mean ± SD.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(A) HEK293 cells stably expressing TAP-vector, TAP-CSAG1, or TAP-CSAG2 were subjected to pull-down followed by SDS-PAGE and LC-MS/MS. Spectral counts (SC) of the identified proteins in TAP-CSAG1 and TAP-CSAG2 pulldowns, but absence in TAP-vector control, are shown.",
    "ncbi_link": "CSAG1: 158511
CSAG2: 102723547"
  },
  {
    "caption": "(B) HEK293FT cells stably expressing HA-SIRT1 were transfected with Myc-CSAG1 or Myc-CSAG2 for 48 h before IP with anti-HA followed by SDS-PAGE and immunoblotting for indicated proteins.",
    "ncbi_link": "HA: 
Myc: 
CSAG1: 158511
CSAG2: 102723547
SIRT1: 23411"
  },
  {
    "caption": "Expression of CSAG2 decreased p53 ac-K382 levels and downregulated the expression of downstream p53 target genes in H460 cells. Cells were treated by either 1 μM doxorubicin (D-E) with 0.4 μM TSA for the indicated times. Cells were then harvested and blotted for the indicated proteins. Quantitation of expression levels is shown (E Ac-p53 K382 levels normalized to total p53, whereas all other proteins were normalized to GAPDH.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Expression of CSAG2 decreased p53 ac-K382 levels and downregulated the expression of downstream p53 target genes in H460 cells. Cells were treated by 20 μM etoposide with 0.4 μM TSA for the indicated times. Ac-p53 K382 levels normalized to total p53, whereas all other proteins were normalized to GAPDH.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Expression of CSAG2 decreased p53 ac-K382 levels and downregulated the expression of downstream p53 target genes in H460 cells. Cells were treated by 20 μM etoposide with 0.4 μM TSA for the indicated times. Cells were then harvested and blotted for the indicated proteins. Quantitation of expression levels is shown G) as the mean ± SD, n=3 biological replicates. Ac-p53 K382 levels normalized to total p53, whereas all other proteins were normalized to GAPDH.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Knockdown of endogenous CSAG2 in HCT116 (H-I) cells increased p53 ac-K382 levels. CSAG2-knockdown stable cells were treated by 1 μM doxorubicin/ 0.4 μM TSA for 6 hr. Cells were then harvested and blotted for the indicated proteins. Quantitation of ac-p53 K382 levels relative to total p53 is shown (I as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Knockdown of endogenous CSAG2 in A375 cells increased p53 ac-K382 levels. CSAG2-knockdown stable cells were treated by 1 μM doxorubicin/ 0.4 μM TSA for 6 hr. Cells were then harvested and blotted for the indicated proteins.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Knockdown of endogenous CSAG2 in A375 cells increased p53 ac-K382 levels. CSAG2-knockdown stable cells were treated by 1 μM doxorubicin/ 0.4 μM TSA for 6 hr. Cells were then harvested and blotted for the indicated proteins. Quantitation of ac-p53 K382 levels relative to total p53 is shown K) as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(L-M) Re-expression of CSAG2 rescued p53 ac-K382 levels in CSAG2 knockdown stable cell lines. Myc-CSAG2 was transfected in HCT116 (L) or A375 (M) CSAG2 knockdown stable cell lines. Cells were treated with 1 μM doxorubicin/ 0.4 μM TSA for 6 hr and then blotted for the indicated proteins. Quantitation of ac-p53 K382 levels relative to total p53 is shown as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "Myc: 
CSAG2: 102723547"
  },
  {
    "caption": "(N) CSAG2 does not enhance anchorage-independent growth of HCT116 p53-null cells. CSAG2 was stably expressed in isogenic HCT116 p53-wild-type or p53-null cells. Anchorage-independent growth in soft agar colony formation assays was determined after 14 days. The number of colonies was quantified, normalized to each vector control cell line, and is shown as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "(A) Knockdown of SIRT1 abolished CSAG2-mediated decrease in ac-p53 K382. CSAG2 over-expressing HCT116 were transfected with SIRT1 siRNA for 72 hr before doxorubicin/TSA treatment for 6 hr. Cell lysates were blotted for the indicated proteins.",
    "ncbi_link": "CSAG2: 102723547
SIRT1: 23411"
  },
  {
    "caption": "(B) Inhibition of SIRT1 enzymatic activity blocked CSAG2-induced decrease in p53 ac-K382. CSAG2 over-expressing HCT116 cells were treated with 1 μM doxorubicin/ 0.4 μM TSA with or without 1 μM EX-527 for 6 hr. Cell lysates were blotted for the indicated proteins.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Inhibition of SIRT1 enzymatic activity prevents CSAG2-knockdown increase in p53 ac-K382. CSAG2-knockdown stable cells were treated by 1 μM doxorubicin/ 0.4 μM TSA with or without 1 μM EX-527 for 6 hr. Cells were then harvested and blotted for the indicated proteins (C)",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Inhibition of SIRT1 enzymatic activity prevents CSAG2-knockdown increase in p53 ac-K382. CSAG2-knockdown stable cells were treated by 1 μM doxorubicin/ 0.4 μM TSA with or without 1 μM EX-527 for 6 hr. Cells were then harvested and blotted for the indicated proteins and quantitated (D; n=3 biological replicates). Data shown as mean ± SD.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(G) Inhibition of SIRT1 activity abolished CSAG2-induced anchorage-independent growth. Soft agar colony formation assays were performed in control or CSAG2 over-expressing HCT116 cells with or without EX-527 treatment. Data are represented as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(H) Summary of region on CSAG2 required for SIRT1 interaction. HEK293FT cells stably expressing HA-SIRT1 were transfected with indicated CSAG2 constructs for 48 h before IP with anti-HA followed by SDS-PAGE and immunoblotting for anti-Myc.",
    "ncbi_link": "HA: 
CSAG2: 102723547
SIRT1: 23411"
  },
  {
    "caption": "(J) CSAG2 Δ37 mutant does not regulate p53 ac-K382 levels. Cells were transfected with the indicated Myc-CSAG2 constructs for 48 hr before being treated with 1 μM doxorubicin/ 0.4 μM TSA. Cell lysates were blotted for the indicated proteins.",
    "ncbi_link": "Myc: 
CSAG2: 102723547"
  },
  {
    "caption": "(K) CSAG2 Δ37 fails to promote anchorage-independent growth of H460 cells. Soft agar colony formation assays were performed in CSAG2-negative H460 cells stably expressing CSAG2 wild-type or CSAG2 Δ37 mutant (n=3 biological replicates). Data are represented as the mean ± SD.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Control or CSAG2 expressing H460 cells were treated with the indicated concentrations of doxorubicin (A) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Control or CSAG2 expressing H460 cells were treated with the indicated concentrations of H2O2 (B) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "shCTRL, shCSAG2-1, or shCSAG2-2 stable HCT116 cells were treated with the indicated concentrations of doxorubicin (C) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "shCTRL, shCSAG2-1, or shCSAG2-2 stable HCT116 cells were treated with the indicated concentrations of H2O2 (D) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(G) H460 cells were transfected with wild type, Δ37, or Δ63 CSAG2 for 48 hr. Cells were then treated with the indicated concentrations of H2O2 for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(H) Inhibition of SIRT1 activity abolished CSAG2 induced cell survival under genotoxic stress. CSAG2 over-expressing H460 cells were treated with the indicated concentrations of H2O2 with or without 1 μM EX-527 for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "Control or Myc-CSAG2 expressing HCT116 p53 -/- cells were treated with the indicated concentrations of H2O2 (I) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "Myc: 
CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "Control or Myc-CSAG2 expressing HCT116 p53 -/- cells were treated with the indicated concentrations of doxorubicin (J) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "Myc: 
CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "shCTRL, shCSAG2-1, or shCSAG2-2 stable HCT116 p53 -/- cells were treated with the indicated concentrations of H2O2 (K) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "shCTRL, shCSAG2-1, or shCSAG2-2 stable HCT116 p53 -/- cells were treated with the indicated concentrations of doxorubicin (L) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "Control or Myc-CSAG2 expressing H1299 (p53 mutant) cells were treated with the indicated concentrations of H2O2 (M) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "Myc: 
CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "Control or Myc-CSAG2 expressing H1299 (p53 mutant) cells were treated with the indicated concentrations of doxorubicin (N) for 24 hr before cell viability was determined by alamarBlue (n=6 biological replicates).",
    "ncbi_link": "Myc: 
CSAG2: 102723547
p53: 7157"
  },
  {
    "caption": "(A) CSAG2 does not alter SIRT1 protein levels. HEK293FT cells were transfected with different amounts of Myc-CSAG2 for 48 hr before cells lysates were harvested and immunoblotted for indicated proteins.",
    "ncbi_link": "Myc: 
CSAG2: 102723547"
  },
  {
    "caption": "(B) CSAG2 does not alter SIRT1 subcellular location. U2OS cells were transfected with or without mcherry-CSAG2 for 48 hr before fixation, SIRT1 immunostaining, and imaging. Scale bar: 10 µm.",
    "ncbi_link": "mcherry: 
CSAG2: 102723547"
  },
  {
    "caption": "(C) Summary of results mapping interaction region of SIRT1 recognized by CSAG2. HEK293FT cells stably expressing HA-CSAG2 were transfected with indicated Myc-SIRT1 constructs for 48 h before IP with anti-HA followed by SDS-PAGE and immunoblotting for anti-Myc.",
    "ncbi_link": "HA: 
Myc: 
CSAG2: 102723547
SIRT1: 23411"
  },
  {
    "caption": "(H-I) U2OS cells were transfected with Myc-Vector or Myc-CSAG2 for 48 hr before being treated with or without 0.4 μM TSA for 6 hr. Cell lysates were blotted for the indicated proteins (H). Quantitation of expression levels of acetylated Histone relative to total Histone is shown as the mean ± SD, n=3 biological replicates. White circles indicate Myc-Vector and black circles indicate Myc-CSAG2.",
    "ncbi_link": "Myc: 
CSAG2: 102723547"
  },
  {
    "caption": "(J) HeLa, U2OS, or HCT116 cells were transfected with Myc-Vector or Myc-CSAG2 for 48 hr. Cell lysates were blotted for the indicated proteins. Quantitation of expression levels of acetylated Histone relative to total Histone is shown as the mean ± SD, n=3 biological replicates. White circles indicate Myc-Vector and black circles indicate Myc-CSAG2.",
    "ncbi_link": "Myc: 
CSAG2: 102723547"
  },
  {
    "caption": "(K) Knockdown of endogenous CSAG2 in A375 cells increased ac-H4K16 levels. Cell lysates were blotted for the indicated proteins. Quantitation of expression levels of ac-H4K16 relative to total H4 is shown as the mean ± SD, n=3 biological replicates.",
    "ncbi_link": "CSAG2: 102723547"
  },
  {
    "caption": "(A , B) A brightfield image showing the zebrafish thyroid gland along with surrounding tissue. The thyroid follicles reside in the soft tissue surrounding the ventral aorta, which extends from the outflow tract of the heart into the gills towards the basibranchial cartilage in the lower jaw. The thyroid follicular cells, or thyrocytes, are labeled in green in the Tg(tg:nls-mVenus-NTR) transgenic line (B'). Scale bars: 500 µm",
    "ncbi_link": "mVenus: 
tg: 567631"
  },
  {
    "caption": "(C) Maximum intensity projection of 3D confocal stack obtained from the dissected thyroid gland of Tg(tg:nls-EGFP) animal and labeled with DAPI. (D) Confocal scan of a transverse section across the dissected thyroid gland from Tg(tg:nls-EGFP) animal at 3 mpf. Sections were stained with DAPI to visualize cells surrounding thyroid follicles. (E) Boxplot depicting the proportion of thyrocytes present in transverse sections obtained from three Tg(tg:nls-EGFP) animals at 3 mpf. Each dot represents a transverse section. The Tukey boxplot marks the 25th percentile, median and 75th percentile with whiskers extending from smallest to largest values. ",
    "ncbi_link": "EGFP: 
tg: 567631"
  },
  {
    "caption": "(F , G) Representative FACS plot of single cells from Tg(tg:nls-mVenus-T2A-NTR) animals at 2 mpf (F) and 8 mpf (G). Calcein (Pacific Blue) labels live cells, while green fluorescence (FITC) labels thyrocytes. Percentage values represent proportion of calcein+ thyrocytes within total calcein+ cells.",
    "ncbi_link": "mVenus: 
tg: 567631"
  },
  {
    "caption": "(A) A t-SNE plot displaying the 6249 single-cells profiled in the zebrafish thyroid gland atlas. The colors represent cell clusters denoting a specific cell-type. (B-D) Cluster #1 represents the thyrocytes that express tg, slc5a5 (NIS) and tpo. The color scale represents the normalized expression counts for each gene ranging from lowest (grey) to highest (red). ",
    "ncbi_link": "slc5a5: 561445
NIS: 561445
tg: 567631
tpo: 569363"
  },
  {
    "caption": "(A-D) Images show immunofluorescence labeling of thyroid gland from adult zebrafish. Transverse sections were utilized for imaging. The organ was isolated from tissue-specific transgenic lines to allow marking of a particular cell-type adjacent to the thyroid follicle. Blood vessels were marked using Tg(kdrl:EGFP) (A), macrophages using Tg(mpeg1.1:mCherry) (B) and stroma using Tg(col1a2:mCherry) (C). Thyrocytes were labeled with pax2amKO2 expression in (A) and Tg(tg:nls-EGFP) expression in (B - C). (D) NFE was labeled using antibody against TP63 in sections of the thyroid gland isolated from Tg(tg:nls-EGFP) animals. Gills are marked based on their morphological appearance. DAPI labels nuclei. Scale bars: 10 µm (A - B), 50 µm (C - D).",
    "ncbi_link": "EGFP: 
mCherry: 
col1a2: 336471
kdrl: 796537
mpeg1.1: 335407
tg: 567631"
  },
  {
    "caption": "(A) Dot plot depicting expression entropy on Y-axis against average gene expression on X-axis for the thyrocyte population. Each dot depicts a gene, with red dots depicting genes that show statistically significant (p-value < 0.05) difference in entropy from expected value. Expected value is represented by black regression line. pax2a and ctsba are marked on the graph.",
    "ncbi_link": "ctsba: 406645
pax2a: 30425"
  },
  {
    "caption": "(B) t-SNE plot of the thyrocyte cluster with expression of tg, pax2a and ctsba. The color scale represents the normalized expression counts for each gene ranging from lowest (yellow) to highest (red). (B') Histogram overlaid with density plots depicting the distribution of normalized gene expression for tg, pax2a and ctsba. ",
    "ncbi_link": "ctsba: 406645
pax2a: 30425
tg: 567631"
  },
  {
    "caption": "(B) Whole mount immunofluorescence of 9.5hpf pax2amKO2 embryos stained with anti-mKO2 antibody (red) and anti-PAX2A antibody (green). Anterior is to the left, and dorsal side is to the top. Scale bar: 0.1 mm.",
    "ncbi_link": "mKO2: 
pax2a: 30425"
  },
  {
    "caption": "(C) Whole mount immunofluorescence of 55 hpf pax2amKO2; Tg(tg:nls-EGFP) stained with PAX2A antibody (PAX2A-Ab) displays an overlap of mKO2 and PAX2A-Ab signal. The otic vesicle (OV), mid-hindbrain barrier (MHB), interneurons (IN) and thyroid gland (THY) is labelled. White dashed line represents the outline of the zebrafish larvae. Scale bar: 100 µm. Anterior to the right.",
    "ncbi_link": "EGFP: 
mKO2: 
pax2a: 30425
tg: 567631"
  },
  {
    "caption": "(D - F) Confocal microscopy imaging of a sagittal section of a 55 hpf pax2amKO2 (red); Tg(tg:nls-EGFP) (green) embryos immunostained with PAX2A antibody (cyan) showing co-localization of mKO2 and pax2a in the pronephros (D), thyroid gland (E) and mid-hindbrain barrier (F). In the thyroid gland, mKO2 (red), PAX2A-Ab (cyan) and thyrocyte-specific GFP (green) show co-localization. Scale bar: 50 µm.",
    "ncbi_link": "EGFP: 
mKO2: 
pax2a: 30425
tg: 567631"
  },
  {
    "caption": "(G , H) Snapshots from live imaging of 55 hpf pax2amKO2; Tg(tg:nls-EGFP) embryos injected with sgRNA targeting pax2a coding sequence. The anterior part of a representative control embryo (G) is shown alongside a representative crispant (H). Crispants display a strong reduction of mKO2 fluorescence, as well as an absence of GFP signal suggesting absence of thyroid (THY) tissue. White dashed line represents the outline of the zebrafish larvae. Scale bar: 100 µm. Anterior to the right.",
    "ncbi_link": "EGFP: 
mKO2: 
pax2a: 30425
tg: 567631"
  },
  {
    "caption": "(A-D) Analysis of 3 mpf thyroid gland from pax2amKO2 zebrafish shows heterogeneity in pax2a reporter expression. (A) Whole mount confocal imaging of a 3 mpf pax2amKO2 thyroid labelled with mKO2 (red), E-cadherin (cyan, not shown in 'A' for clarity reasons) and DAPI (dark blue) for nuclear localisation. (B - D) Optical sections of three follicles, with mKO2-Low cells labelled with arrows. E-cadherin (B' - D') and DAPI (B'' - D'') staining shows that absence of mKO2 signal does not correspond to an absence of cells. Anterior to the bottom of the pictures.",
    "ncbi_link": "mKO2: 
pax2a: 30425"
  },
  {
    "caption": "(E,F) (E) Confocal image of thyroid gland section from Tg(tg:nls-EGFP) at 4 mpf stained with PAX2A antibody and DAPI. The dotted region is displayed at high magnification in (F). Arrows marks thyrocytes displaying low PAX2A staining. Notably, PAX2A-Low thyrocytes display tg-driven EGFP expression, demonstrating their differentiated status.",
    "ncbi_link": "EGFP: 
tg: 567631"
  },
  {
    "caption": "(A - C) Cells from the thyroid gland of 5 mpf Tg(tg:nls-GFP); pax2amKO2 animals were labelled with calcein (live cell marker) and analysed using FACS. (A) A FACS plot showing calcein on Y-axis and GFP on X-axis. The box encompassing the GFP+ cells represents the thyrocyte population, which was gated for further analysis. (B) Histogram showing the distribution of GFP intensity in thyrocytes. (C) Histogram showing the distribution of mKO2 intensity in thyrocytes. Thyrocytes were selected by gating for GFP+ population. Horizontal lines indicate the mKO2-Low and mKO2-High expression level, with percentage values representing proportion of thyrocytes with mKO2-Low and mKO2-High expression.",
    "ncbi_link": "mKO2: 
pax2a: 30425"
  },
  {
    "caption": "(D , E) RNA-Seq. analysis of transcriptome isolated from pax2amKO2-High and pax2amKO2-Low subpopulations. (D) Volcano plot representing the differential expression of genes between the two thyrocyte subpopulations. Dots for pax2a, tg, mKO2 and EGFP are marked. Dots for genes that display significant differential expression (DESeq2, adjusted p-value < 0.05) are coloured. (E) Heatmap displaying the expression of selected genes in the two subpopulations. Biological replicates are represented by individual columns.",
    "ncbi_link": "EGFP: 
mKO2: 
pax2a: 30425
tg: 567631"
  },
  {
    "caption": "293T cells were transfected with the indicated plasmid DNAs for 24 hr. The cell lysates were prepared and pulled down with Strep bead for 2 hr. Co-precipitated proteins were determined by immunoblot assay. WT, PARS1 wild type; MT, PARS1 FA/EA/RL.",
    "ncbi_link": "PARS1: "
  },
  {
    "caption": "G, H. WI-26 VA4 cells stably expressing each of EV (empty vector) or PARS1 FA/EA/RL mutant were incubated with the indicated compounds for 72 hr. Dose-response curves of the compounds for collagen levels and cytotoxicity were determined and relative ratio of CC50 to the IC50 of collagen for HF (G) and DWN12088 (H) were calculated. The IC50 values were calculated using GraphPad Prism 7.0 (collagen ELISA, n = 12 from four independent experiments (triplicate for each experiment); cytotoxicity assay, n = 8 from four independent experiments (duplicate for each experiment); Welch's t test; ***P < 0.001; mean ± SEM).",
    "ncbi_link": "PARS1: "
  },
  {
    "caption": "K. WI-26 VA4 cells stably expressing each of EV or PARS1 FA/EA/RL mutant were incubated with the indicated compounds in the presence of TGF-β for 72 hr. The levels of the indicated proteins were determined by immunoblotting. The percentage of proline in polypeptide sequences is shown on the right side of immunoblot images.",
    "ncbi_link": "PARS1: "
  },
  {
    "caption": "(A) RT-PCR analysis for temporal expression  of sinhcaf  mRNA during embryogenesis and early larval  developmental stages. NC indicates the no template control.",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(B)  Time-course expression   of sinhcaf  revealed by whole-mount in situ hybridization. Scale bars, 100 μ",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(C) RT-PCR analysis for spatial expression  of sinhcaf  mRNA in adult tissues.",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(E) Relative mRNA level of sinhcaf  in  bud  stage WT and MZsinhcaf -/- mutant embryos  as measured by  RT-qPCR. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using unpaired two-tailed Student's t-test.",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(G) Relative mRNA level of sinhcaf  in 10hpf or 24hpf WT and Tg(CMV:EGFP;CMV:sinhcaf) embryos  as measured by RT-qPCR. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using 2-way ANOVA followed by Holm-Sidak post-hoc test.",
    "ncbi_link": "EGFP: 
sinhcaf: 563991"
  },
  {
    "caption": "(H) Percentage of male zebrafish  in WT (n = 274), MZsinhcaf -/- (n = 166), Tg(CMV:EGFP;CMV:sinhcaf) (n = 158) and MZsinhcaf -/-;Tg(CMV:EGFP;CMV:sinhcaf) (n = 135) adult zebrafish. Data shown are mean ± SEM (n = the number of fish  analyzed). Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test. The different letters (a, b, c) indicate a significant difference between the means, p<0.05.",
    "ncbi_link": "EGFP: 
sinhcaf: 563991"
  },
  {
    "caption": "(A and B)  Whole-mount in situ hybridization was performed in WT, MZsinhcaf -/-, Tg(CMV:EGFP;CMV:sinhcaf) and MZsinhcaf -/-;Tg(CMV:EGFP;CMV:sinhcaf) zebrafish embryos  with PGCs  markers nanos3  (A) and vasa  (B). Scale bars, 100 μm. (C) Quantitative analysis of PGCs  in bud  stage WT, MZsinhcaf -/-, Tg(CMV:EGFP;CMV:sinhcaf) and MZsinhcaf -/-;Tg(CMV:EGFP;CMV:sinhcaf) zebrafish embryos. Data shown are mean ± SEM (n = 10, the number of embryos  analyzed). Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test. The different letters (a, b, c) indicate a significant difference between the means, p<0.05.",
    "ncbi_link": "EGFP: 
vasa: 30263
nanos3: 140631
sinhcaf: 563991"
  },
  {
    "caption": "(D) Maximal intensity projection of a confocal z-stack of 24hpf Tg(piwil1:EGFP) and MZsinhcaf -/-; Tg(piwil1:EGFP) zebrafish embryos, dorsal views. Arrowheads point to PGCs. Scale bars, 100 μm. (E) Quantitative analysis of PGCs  in 24hpf Tg(piwil1:EGFP) and MZsinhcaf -/-; Tg(piwil1:EGFP)zebrafish embryos. Data shown are mean ± SEM (n = 13, the number of embryos  analyzed). Statistical analysis was performed using unpaired two-tailed Student's t-test.",
    "ncbi_link": "EGFP: 
piwil1: 368200
sinhcaf: 563991"
  },
  {
    "caption": "(A) Whole-mount in situ hybridization  was performed in  4-cell stage WT, MZsinhcaf -/- zebrafish embryos  with germ plasm marker vasa. Red arrowheads point to cleavage furrows in the 4-cell embryos. Scale bars, 100 μm",
    "ncbi_link": "vasa: 30263
sinhcaf: 563991"
  },
  {
    "caption": "(B) Relative mRNA levels of germ plasm genes vasa, dnd, nanos3, dazl  and buc  in WT and MZsinhcaf -/- mutant eggs, respectively, as measured by RT-qPCR. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using 2-way ANOVA followed by the Holm-Sidak post-hoc test; NS, no significant difference.",
    "ncbi_link": "buc: 334375
dazl: 58039
vasa: 30263
dnd: 373074
nanos3: 140631
sinhcaf: 563991"
  },
  {
    "caption": "(C) Maximal intensity projection of a confocal  z-stack of 4-cell stage WT and MZsinhcaf -/- zebrafish embryos  injected with GFP-Buc  and RFP  mRNA. White arrowheads point to  cleavage furrows of 4-cell embryos. Scale bars, 100 μm.",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
sinhcaf: 563991"
  },
  {
    "caption": "(D) Relative GFP-Buc  density at the cleavage furrow  of  4-cell stage  WT and MZsinhcaf -/- zebrafish embryos  injected with GFP-Buc  and RFP  mRNA. Statistical analysis was performed using unpaired two-tailed Student's t-test. Data shown are mean ± SEM (n = 12, the number of embryos  analyzed).",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
sinhcaf: 563991"
  },
  {
    "caption": "(F) Western blots  for GFP-Buc  expression  in 4-cell stage WT and MZsinhcaf -/- zebrafish embryos  injected with GFP-Buc  and RFP mRNA",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
sinhcaf: 563991"
  },
  {
    "caption": "(A, B and C) Co-immunoprecipitation of zebrafish Sinhcaf-GFP  with HA-Hdac1  (A), HA-Sin3a  (B) or HA-Sap18  (C) in HEK293Tcells transfected with both Sinhcaf-GFP  and HA-Hdac1  (A), HA-Sin3a (B) or HA-Sap18  (C) plasmids.",
    "ncbi_link": "GFP: 
HA: 
Hdac1: 192302
Sap18: 393693
Sin3a: 323346///563090
Sinhcaf: 563991"
  },
  {
    "caption": "(D) Relative mRNA level of sinhcaf  in zebrafish PG, PV, EV, MV  and FG follicles  was measured using RT-qPCR. Data shown are mean ± SEM (n = 3, biological replicates). Data information: EV, early vitellogenic stage (early stage III); FG, full-grown stage  (late stage III); MV, mid vitellogenic stage (mid stage III); PG,  primary growth (stage I); PV, previtellogenic stage (stage II).",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(E and F) Western blots for acetyl-histone H3  (K9) (Ace-H3-K9),  histone H3 in WT (E) or MZsinhcaf -/- (F) PG, PV, EV, MV  and FG follicles. α-tubulin was used as a loading control. Data information: EV, early vitellogenic stage (early stage III); FG,  full-grown stage  (late stage III); MV, mid vitellogenic stage (mid stage III); PG,  primary growth (stage I); PV, previtellogenic stage (stage II).",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(G and H) Statistical analysis of the relative levels of Ace-H3-K9 in WT (G) or MZsinhcaf -/- (H) PG, PV, EV, MV  and FG follicles. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test. The different letters (a, b, c) indicate a significant difference between the means, p<0.05. Data information: EV, early vitellogenic stage (early stage III); FG, full-grown stage (late stage III); MV, mid vitellogenic stage (mid stage III); PG, primary growth  (stage I); PV, previtellogenic stage (stage II).",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(I, J and K) Western blots for Ace-H3-K9 and H3  in WT and MZsinhcaf -/- EV  (I), MV  (J) and FG  (K) follicles. α-tubulin  was used as a loading control. Data information: EV, early vitellogenic stage (early stage III); FG, full-grown stage (late stage III); MV, mid vitellogenic stage (mid stage III)",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(L) Western blots for Ace-H4-K5, Ace-H3-K18 and H3  in WT and MZsinhcaf -/- FG follicles. α-tubulin was used as a loading control. Data information: FG, full-grown stage (late stage III)",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(M, N and O) Statistical analysis of the relative levels of Ace-H3-K9I n WT and MZsinhcaf -/- EV  (M), MV  (N) and FG  (O) follicles. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using unpaired two-tailed Student's t-test. Data information: EV, early vitellogenic stage (early stage III); FG, full-grown stage (late stage III); MV, mid vitellogenic stage (mid stage III)",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(P and Q) Statistical analysis of the relative levels of Ace-H3-K18 (P) and Ace-H4-K5 (Q) in WT and MZsinhcaf -/- FG follicles. Data shown are mean ± SEM (n = 3, biological replicates). Statistical analysis was performed using unpaired two-tailed Student's t-test. Data information: ; FG,  full-grown stage (late stage III)",
    "ncbi_link": "sinhcaf: 563991"
  },
  {
    "caption": "(A) Maximal intensity projection of a confocal  z-stack of 24hpf Tg(piwil:egfp), Tg(piwil:egfp) injected with kif26ab MO   and Tg(piwil:egfp) injected with control MO embryos. (B) Quantitative analysis of PGCs  in 24hpf Tg(piwil:egfp) (n = 11), Tg(piwil:egfp) injected with kif26ab MO  (n = 12) and Tg(piwil:egfp) injected with control MO  (n = 13) embryos. Data shown are mean ± SEM (n = the number of embryos  analyzed).",
    "ncbi_link": "egfp: 
kif26ab: 58004
piwil: 368200"
  },
  {
    "caption": "(C) Maximal intensity projection of a confocal  z-stack of  4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA, GFP-Buc  mRNA + RFP mRNA + Control MO  and GFP-Buc  mRNA + RFP  mRNA + kif26ab MO. White arrowheads point to cleavage furrows of  4-cell embryos.",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004"
  },
  {
    "caption": "(D) Relative GFP-Buc  density at the cleavage furrow  of 4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA (n = 11), GFP-Buc  mRNA + RFP  mRNA + Control MO  (n = 11) and GFP-Buc  mRNA + RFP  mRNA + kif26ab MO  (n = 10). Data shown are mean ± SEM (n = the number of embryos analyzed).",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004"
  },
  {
    "caption": "(E) Statistical analysis of the relative levels of GFP-Buc/a-Tubulin. Data shown are mean ± SEM (n = 3, biological replicates). (F)  Western blots for GFP-Buc  expression in 4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA, GFP-Buc  mRNA + RFP  mRNA + Control MO  and GFP-Buc  mRNA + RFP  mRNA + kif26ab MO. Data information: Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test. Scale bars, 100 μm.",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004"
  },
  {
    "caption": "(G) Maximal intensity projection of a confocal  z-stack of MZsinhcaf -/- or WT  4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA or GFP-Buc  mRNA + RFP  mRNA + kif26ab  mRNA. White arrowheads point to cleavage furrows  of 4-cell embryos.",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004
sinhcaf: 563991"
  },
  {
    "caption": "(H) Relative GFP-Buc density at the  cleavage furrow  of MZsinhcaf -/- (n = 12) or WT (n = 13) 4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA or GFP-Buc  mRNA + RFP  mRNA + kif26ab  mRNA. Data shown are mean ± SEM (n = the number of embryos  analyzed).",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004
sinhcaf: 563991"
  },
  {
    "caption": "(I) Statistical analysis of the relative levels of GFP-Buc/a-Tubulin. Data shown are mean ± SEM (n = 3, biological replicates). (J) Western blots for GFP-Buc  expression in MZsinhcaf -/- or WT 4-cell stage embryos injected with GFP-Buc  mRNA + RFP  mRNA, GFP-Buc  mRNA + RFP  mRNA + Control MO  and GFP-Buc mRNA + RFP  mRNA + kif26ab MO. Data information: Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test. Scale bars, 100 μm.",
    "ncbi_link": "GFP: 
RFP: 
Buc: 334375
kif26ab: 58004
sinhcaf: 563991"
  },
  {
    "caption": "B, single optical plane in the HPuHG  of wildtype mice  and Alk1EndoKO mice  showing dramatic vascular  defect in Alk1EndoKO mice. Severely tangled and tortuous vasculatures  were outlined in white dotted rectangles.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "C, 8 μm skin  section of Cre- control (CT) and  Alk1EndoKO mice stained  for Cdh5  (red), Ki67  (green), Erg  (white), and Dapi  (blue). Examples of Cdh5/Ki67  double positive cells were enlarged in the white dotted inset for visualization purposes.",
    "ncbi_link": "Alk1: 11482
Cre: 2777477"
  },
  {
    "caption": "D-G, Error bars represent standard deviation. Each bar represents one individual mouse, and each dot represents measurement from one image. N = 3 mice  per group, and n = 9-16 images per mouse. Restricted maximum likelihood (REML) analysis with unbounded variance components was used as statistical test and individual mouse  was treated as random effect to take into the account of mouse-to-mouse  variability. D, Quantification of number of ECs  in HPuHG  area from C. E, Percentage of proliferative ECs  (percentage of Ki67+ Cdh5+ cells in total Cdh5+ cells) in HPuHG  from C. F, Percentage of proliferative ECs  (percentage of Ki67+/Cdh5+ cells in total skin Cdh5+ cells) from C G, Percentage of proliferative ECs  (percentage of BrdU+ Cdh5+ cells in total Cdh5+ cells) in total skin  from PD17-24 BrdU-pulsed CT and Alk1EndoKO mice",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "A-C, Immunofluorescence staining  images of 12 μm skin  section from PD17 induced PD20 telogen  CT, PD25 early anagen  CT, and PD25 telogen Alk1EndoKO mice stained  for Endomucin  (EMCN, red), CD31  (green), and Dapi  (blue). HPuHG  region was outlined in yellow dotted lines. D-F, Error bars represent standard deviation. Each bar represents one individual mouse, and each dot represents measurement from one image. N = 3 mice  per group, and n = 8-9 images per mouse. Restricted maximum likelihood (REML) analysis with unbounded variance components was used to calculate p-values and individual mouse  was treated as random effect to take into the account of mouse-to-mouse  variability. D, Quantification of EMCN+/CD31+ area from images like those in A-C, shown as percentage of BV  in the HPuHG. E, Quantification of absolute EMCN+ area (e.g. BV  area) in HPuHG  in images like those in A-C. F, Quantification of EMCN-/CD31+ area from images like those in A-C as LV  area in the HPuHG.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "G-J, Maximum projection through optical Z-stacks of 60 μm skin  sections from mice TM-induced at PD17 and sacrificed at PD20 telogen  CT, PD25  early anagen  CT, PD32 Anagen  CT, and PD25 telogen Alk1EndoKO mice stained  for VEGFR3  (red), LYVE1  (green), and Dapi  (blue). Lymphatic capillaries  were outlined in white dotted lines. K, Quantification of lymphatic capillary caliber from images like those in G-J in PD20 telogen CT, PD25 early anagen CT, and PD25 telogen Alk1EndoKO mice  Error bars represent standard deviation. Each bar represents one individual mouse, and each dot represents measurement from one  lymphatic capillary. N = 3 mice  per group, and n = 9-25 measurements per mouse. Restricted maximum likelihood (REML) analysis with unbounded variance components was used to calculate p-values and individual mouse  was treated as random effect to take into the account of mouse-to-mouse  variability.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "F, Quantification of lymphatic capillary  caliber from images like those in D in CT and Alk1LymphKO mice  Error bars represent standard deviation. Each bar represents one individual mouse, and each dot represents measurement of one lymphatic capillary. N = 3 mice  per group, and n = 13-16 measurements per mouse. Restricted maximum likelihood (REML) analysis with unbounded variance components was used as statistical test and individual mouse  was treated as random effect to take into the account of mouse-to-mouse  variability.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "G, Immunofluorescence  images of 12 μm skin  section of PD17 induced PD25 CT and Alk1LymphKO mice stained  for Ki67  (red), Itga6  (green) and Dapi  (blue) showing representative hair follicle. Hair follicles were outlined with yellow dotted lines. Note Ki67+ cells in the hair germ (HG) area indicative of HFSC  activation. Telogen hair follicle  is defined as no Ki67  in the hair germ. Anagen I is defined as ≤7 Ki67+ cells in the unenlarged hair germ. Anagen II  is defined as >7 Ki67+ cells in the hair germ or enlarged hair germ  with changed shape that starts to enclose the DP. Experiments were repeated at least 2 times with at least 3 skin  sections/each mouse  analyzed with N = 6/4 mice/group. See Table 1 for quantification detail.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "B, Immunofluorescence  image of 12 μm skin  section from CT and  Alk1EndoKO mice  used for RNA-seq stained  for Ki67  (red) and Dapi  (blue) show that HFSCs  are in quiescence.",
    "ncbi_link": "Alk1: 11482"
  },
  {
    "caption": "C, Images of 20 μm skin  section of PD20 and PD25 BMP4-LacZ; Alk1f/f; Cdh5-CreERT2 negative, injected with tamoxifen TM  at PD17 (labelled as CT), and PD20/PD25 Cdh5CreERT2; Alk1f/f; BMP4-LacZ mice  (labelled as Alk1EndoKO) TM  injected at PD17, all stained  for CD31  (IHC  method, brown) and X-gal  (blue). Hair follicles  (HF) were outlined with black dotted lines. Arrows point to X-Gal+ vascular  structure in HPuHG  area.",
    "ncbi_link": "LacZ: 
Alk1: 11482
BMP4: 12159
Cdh5: 12562
Cre: 2777477
ERT2: 2099"
  },
  {
    "caption": "K, Quantification of hair follicle percentage of PD17-induced PD25 CT,  Alk1EndoKO, Alk1 BMP4dKO, and BMP4EndoKO at telogen, anagen I, and  anagen II stages. Telogen hair follicle is defined as no Ki67  in the hair germ. Anagen I is defined as ≤7 Ki67+ cells in the unenlarged  hair germ.  Anagen II is defined as >7 Ki67+ cells in the hair germ or enlarged hair germ with changed shape that starts to enclose the DP. P-value was generated from Chi-square test. See Table 1 for quantification detail.",
    "ncbi_link": "Alk1: 11482
BMP4: 12159"
  },
  {
    "caption": "B.  Western blot  analysis of the   dose-dependent  expression of ZBP1  in HT29  / TO-ZBP1WT and HT29  / TO-ZBP1Zα1α2mut cells treated with indicated concentrations of Dox  for 24 h. Blots  are representative of three biological repeats.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "L. Transwell migration of primary neutrophils  towards conditioned media from HT29  / TO-ZBP1WT cells treated with DMSO  or 500 ng/mL Dox  for 24 hours, or HT29  chemotaxis buffer (control buffer) containing equal volume and amount of DMSO  or Dox  as the conditioned media. Data is presented as individual values with grand mean of the migrated percentage induced by control buffer containing DMSO  or Dox  (n = 10 biological replicates), or conditioned media from DMSO-treated cells (n = 11 biological replicates) or Dox-treated cells (n = 12 biological replicates), where the number of biological replicates is defined by the total number of independent cell cultures tested on primary neutrophils  from four donors. An unpaired t-test was used to test for statistical differences between indicated conditions. **** p < 0.0001.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "M. Transwell migration of primary neutrophils towards conditioned media from HT29  / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  in combination with DMSO  or 20 µM zVAD  + 10 μM Nec1s  for 24 h. Data is presented as individual values with mean and S.E.M. (n = 3 biological replicates of conditioned media). One-way ANOVA and Sidak's multiple comparisons test were used to test for statistical differences between indicated conditions. ns = not significant (p = 0.4129); *** p = 0.0004.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "C. Transwell migration of primary neutrophils towards conditioned media from HT29  / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  in combination with indicated inhibitors for 24 h. Data is presented as individual values with grand mean (n = 3 biological replicates of conditioned media from GSK'872  and NSA-treated wells, n = 6 biological replicates of conditioned media from other conditions). Two-way ANOVA and Sidak's multiple comparisons test were used to test for statistical differences between indicated conditions. **** p < 0.0001; ns = not significant (p > 0.96).",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "D. CXCL8  concentration in the culture media of HT29  / TO-ZBP1WT cells transfected with siRNA targeting mismatch sequence (MM) or RIPK3  and treated with Dox  at indicated concentrations for 24 h. Data is presented as mean with S.E.M. (n = 4 biological replicates). Unpaired t-tests were used to test for statistical differences between indicated conditions. ** p = 0.0079. Cell lysates from one biological replicate were analyzed by Western blotting.",
    "ncbi_link": "RIPK3: 56532
ZBP1: 81030"
  },
  {
    "caption": "E. Cytokine concentration  in the culture media of HT29  / TO-ZBP1WT or HT29  / RIPK1-KO clone aA3 / TO-ZBP1WT cells treated with 0, 50 or 500 ng/mL Dox. data is plotted as mean with S.E.M. (n = 6 biological replicates). Brown-Forsythe and Welch ANOVA tests and Dunnet's T3 multiple comparisons test were used to test for statistical differences between indicated conditions. Cell lysates were analyzed by Western blotting for ZBP1  levels. Blots  are representative of six biological replicates. ns = not significant (p > 0.2); *** p = 0.0003 for CXCL8, p = 0.0008 for CXCL1; **** p < 0.0001.",
    "ncbi_link": "RIPK1: 19766
ZBP1: 81030"
  },
  {
    "caption": "G, NF-κB  activity in HEK293FT  cells with and without stable expression of full-length (FL) RIPK3-2xFV or RIPK3∆C-2xFV (∆C) transfected with dual luciferase  reporters and ZBP1  or empty vector (EV) as indicated. Reporter activities were measured 24 h after transfection. Data is presented as mean with S.E.M (n = 3 biological replicates). One-way ANOVA and Sidak's multiple comparisons test were used to test for statistical differences between indicated conditions. ns = not significant (p > 0.05); **** p<0.0001. (G) Cell lysates were analyzed by Western blotting. Blots  are representative of three biological replicates. Asterisk indicates background signals of the antibody.",
    "ncbi_link": "luciferase: 
RIPK3: 11035
ZBP1: 81030"
  },
  {
    "caption": "A. Western blot  analysis of anti-FLAG  (ZBP1) immunoprecipitation  from HT29  / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  for 16 h. Blots  are representative of three biological replicates. Immunoprecipitated  material was treated or not with USP21  (1 μM) for deubiquitination. Input loaded was 5% for ZBP1  and 1% for co-immunoprecipitants. Asterisk indicates antibody heavy chain signal in IP  samples.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "B. Enrichment of Ub-conjugates by GST-1xUBA   for analysis of ubiquitination  status of RIPK1, ZBP1  and RIPK3  in HT29  / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  for 16h. Blots  are representative of at least three biological replicates. After enrichment, samples were treated or not with USP21  (1 μM) for deubiquitination. Asterisk indicates unspecific bands. Arrows indicate RIPK3  signal.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "C. Enrichment of Ub-conjugates for analysis of the ubiquitination  status of RIPK1  and ZBP1  using GST-1xUBA or linkage-specific SUBs  in HT29  / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  for 16 h.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "D. Enrichment of Ub-conjugates by GST-1xUBA for analysis of ubiquitination  status of RIPK1  and ZBP1  in HT29, HT29  / TO-ZBP1WT and HT29  / RIPK1-KO aA3 / TO-ZBP1WT cells treated with 500 ng/mL Dox  for 16 h. Blots  are representative of four biological replicates. Asterisk indicates antibody background signal.",
    "ncbi_link": "RIPK1: 19766
ZBP1: 81030"
  },
  {
    "caption": "E.  NF-κB activity in HEK293FT  / RIPK3-2xFV cells transfected with dual luciferase  reporters, ZBP1  or EV, and GFP  (Ctrl) or GFP-tagged SUBs  as indicated. Luciferase reporter activities  were measured 24 h after transfection and normalized to GFP+EV-transfected condition. Data is plotted as mean with S.E.M. (n = 4 biological replicates). One-way ANOVA and Sidak's multiple comparisons tests were used to test for statistical differences between the indicated condition and ZBP1/GFP-transfected condition. **** p < 0.0001. Cell lysates were analyzed by Western blotting  to determine expression of ZBP1, GFP  or GFP-tagged SUBs  and Actin. Blots  are representative of three biological replicates.",
    "ncbi_link": "GFP: 
luciferase: 
RIPK3: 11035
ZBP1: 81030"
  },
  {
    "caption": "F, NF-κB activity in HEK293FT  / RIPK3-2xFV cells transfected with dual luciferase  reporters, ZBP1  or EV, and variants of OTULIN.  Luciferase reporter activities  were measured 24 h after transfection and normalized to ZBP1/EV-transfected cells. Data is plotted as mean with S.E.M. Multiple Welch t-tests were used to test for statistical differences between the indicated condition and the ZBP1/EV-transfected condition. (F) n = 4 biological replicates. ** p = 0.0012, ns = not significant (p = 0.2342). Cell lysates were analyzed by Western blotting to determine expression of ZBP1, or OTULIN, and Actin. Blots  are representative of (F) four biological replicates.",
    "ncbi_link": "luciferase: 
OTULIN: 90268
RIPK3: 11035
ZBP1: 81030"
  },
  {
    "caption": "G. NF-κB activity in HEK293FT  / RIPK3-2xFV cells transfected with dual luciferase  reporters, ZBP1  or EV, and variants of CYLD Luciferase reporter activities were measured 24 h after transfection and normalized to ZBP1/EV-transfected cells. Data is plotted as mean with S.E.M. Multiple Welch t-tests were used to test for statistical differences between the indicated condition and the ZBP1/EV-transfected condition. (G) n = 3 biological replicates. * p = 0.0137; ns = not significant (p = 0.8374). Cell lysates were analyzed by  Western blotting to determine expression of ZBP1, CYLD  and Actin. Blots  are representative of (G) three biological replicates.",
    "ncbi_link": "luciferase: 
CYLD: 1540
RIPK3: 11035
ZBP1: 81030"
  },
  {
    "caption": "A. NF-κB  activity in HEK293FT  / RIPK3-2xFV cells transfected with siRNA targeting HOIP  (siHOIP) or a mismatch sequence (siMM), and 48 h later transfected with dual luciferase  reporters and ZBP1  or GFP  (control). Luciferase reporter activities  were measured 24 h after transfection and normalized to the siMM+ZBP1  samples. Data is plotted as mean with S.E.M. (n = 4 biological replicates). A Welch's t-test was used to test for the statistical difference between indicated conditions. **** p < 0.0001. HOIP   knockdown and ZBP1  expression levels were analyzed by Western blotting. Blots  are representative of three biological replicates.",
    "ncbi_link": "GFP: 
luciferase: 
RIPK3: 11035
HOIP: 55072
ZBP1: 81030"
  },
  {
    "caption": "D-F. Western blot  analysis of anti-FLAG  (ZBP1) immunoprecipitation  from HT29  or HT29  / TO-ZBP1WT or HT29  / RIPK1-KO clone aA3 / TO-ZBP1WT cells treated with 0 or 500 ng/mL Dox  for 16 h. Asterisk indicates antibody heavy chain signal in IP  samples. Blots  are representative of at least (D) two and (E-F) three biological replicates.",
    "ncbi_link": "RIPK1: 19766
ZBP1: 81030"
  },
  {
    "caption": "B. Western blot analysis of HCT116  / RIPK3-2xFV cells (FL and ∆C) treated with 100 nM dimerizer. Blots  are representative of two biological replicates.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "D. CXCL8  concentration in the culture media of HCT116  / RIPK3-2xFV cells (WT and RHIMmut) treated with 100 nM dimerizer  for 24 h. In RIPK3-RHIMmut three key residues, VQV, of the RHIM region was changed to AAAA. Data is plotted as mean with S.E.M. (n = 5 biological replicates). One-way ANOVA and Sidak's multiple comparisons tests were used to test for statistical differences between indicated time points. ** p = 0.0011; ns = not significant (p = 0.9301). Inset: Western blot analysis to determine RIPK3  expression levels in one biological replicate. Line indicates that image was cut and spliced to remove non-relevant lanes from the scanned blot.",
    "ncbi_link": "RIPK3: 11035"
  },
  {
    "caption": "H. Relative mRNA levels of CXCL8 in HCT116  / RIPK3-2xFV cells pretreated with 100 nM CpA  for 0.5 h before treatment with 0 or 100 nM dimerizer  for 3 h. Data is presented as mean with S.E.M. (n = 3 biological replicates). One-way ANOVA and Sidak's multiple comparisons tests were used to test for statistical differences between indicated conditions and DMSO+dimerizer-treated condition. **** p < 0.0001. (H) Cell lysates were analyzed by Western blotting for cIAP1  levels. Blots  are representative of two biological replicates.",
    "ncbi_link": "CXCL8: 3576
RIPK3: 11035"
  },
  {
    "caption": "J. Relative CXCL8  mRNA levels in WT or HOIP-knockout HCT116  / RIPK3-2xFV cells treated with 0 or 100 nM dimerizer  for 3 h. Data is plotted as mean with S.E.M. (n = 3 biological replicates). A Welch's t-test was used to test for the statistical difference as indicated. *** p = 0.0010. Cell lysates were loaded for Western blot  analysis.",
    "ncbi_link": "CXCL8: 3576
RIPK3: 11035
HOIP: 55072"
  },
  {
    "caption": "K. Relative CXCL8  mRNA levels in HCT116  / Tet-On-GFP-K63-SUB  / RIPK3-2xFV, HCT116  / Tet-On-GFP-M1-SUB  / RIPK3-2xFV and HCT116  / Tet-On-GFP  / RIPK3-2xFV cells treated with 0 or 100 ng/mL Dox  for 48 h before stimulated with 0 or 100 nM dimerizer  for 3 h. Data is presented as mean with S.E.M. (n = 4 biological replicates). Brown-Forsythe and Welch ANOVA tests and Dunnet's T3 multiple comparisons test were used to test for statistical differences between indicated conditions. ns = not significant (p = 0.9997); ** p = 0.0030; * p = 0.0366. Cells were analyzed by Western blotting  for the inducible-expression levels of GFP  (control) and GFP-SUBs. Blots are representative of three biological replicates.",
    "ncbi_link": "GFP: 
CXCL8: 3576
RIPK3: 11035"
  },
  {
    "caption": "M. Relative CXCL8  mRNA levels in HCT116  / RIPK3-2xFV cells stably knocked down against mismatch (shMM) or two different sites of  caspase-8 (shCASP8-A and shCASP8-B), pretreated with DMSO, 10 µM Nec1s, 10 µM GSK'872 or 1 µM NSA  for 1h followed by treatment with 0 or 100 nM dimerizer  for 3h. Data is plotted as mean with S.E.M. (n = 3 biological replicates). Two-way ANOVA and Tukey's multiple comparison tests were used to test for statistical differences between indicated conditions. *** p = 0.0001; ** p = 0.0035. Cell lysates from one biological replicate were analyzed by Western blotting to determine caspase-8 levels.",
    "ncbi_link": "CASP8: 841
caspase-8: 841
CXCL8: 3576
RIPK3: 11035"
  },
  {
    "caption": "A. Western blot analysis of ZBP1, RIPK1, RIPK3, MLKL  levels in Calu-3  cell lines with stable expression of shRNAs targeting ZBP1  or a mismatch sequence (shMM), untreated (NT) or treated with 10 ng/mL IFNβ  for 48 h. Blots  are representative of two biological replicates.",
    "ncbi_link": "ZBP1: 81030"
  },
  {
    "caption": "somatic hypermutation (SHM) count (E) in IGHV3-21 and IGHV3-33 genes from MBCs",
    "ncbi_link": "IGHV3-21: 28444
IGHV3-33: 28434"
  },
  {
    "caption": "(C) VH SHM load of VH3-21 and non-VH3-21 mAbs. mAbs with unmutated VH are highlighted in green.",
    "ncbi_link": "non-VH3-21: 
VH3-21: 28444"
  },
  {
    "caption": "(D) Amino acid (aa) VH replacement (red bars) and silent (black bars) SHM in VH3-21 mAbs (n=113). FWR, framework region; CDR, complementarity-determining region.",
    "ncbi_link": "VH3-21: 28444"
  },
  {
    "caption": "(D) C-CSP reactivity of the α-TSR-specific mAb 1710 in a blocking ELISA with C-CSP-specific VH3-21 (n=21; upper panel) or non-VH3-21 (n=17; lower panel) mAbs with the indicated SPR affinities. mAb 1710 binding without blocking (blue) and after self-blocking (gold) is shown for comparison.",
    "ncbi_link": "non-VH3-21: 
VH3-21: 28444"
  },
  {
    "caption": "(B) The Western blot analysis of GFP, Spd2 and αTub (loading control) in the brain extracts from wild type (Oregon R, OR), Spd2WT-OE and Spd2DK-OE third instar larva. Representative immune blot images are shown on the left. The signal intensities of Spd2 bands were quantified and normalised against αTub values. The values relative to control of each biological replicate (n = 2) and their means are shown as dots and bars, respectively, in a scatted dot plot on the right. The numbers above the bars indicate means ± Range. GFP-Spd2DK proteins in Spd2DK-OE larval brain extracts showed approximately 2.04-fold higher accumulation than GFP-Spd2WT proteins in Spd2WT-OE brain extracts. (C) The Western blot analysis of Spd2, CycB and αTub in OR, fzrRNAi, Spd2WT-RES and Spd2DK-RES brain extracts. The signal intensities of Spd2 bands were quantified and normalised against αTub values. The values relative to control and their means are presented in a scatted dot plot on the right (biological replicate n = 2). Means ± Range are shown above the bars. RFP-Spd2DK proteins in Spd2DK-RES larval brain extracts showed approximately 2.08-fold higher accumulation than RFP-Spd2WT proteins in Spd2WT-RES brain extracts.",
    "ncbi_link": "GFP: 
RES: 
RFP: 
fzr: 45922
Spd2: 39850"
  },
  {
    "caption": "(D) Larval brains of OR, Spd2WT-RES, fzrRNAi and Spd2WT-OE flies were stained by an anti-Spd2 antibody. Representative images of NBs are shown on the top. Scale bar: 10 µm. The local signal intensities of Spd2 immunofluorescence at the centrosomes and in the cytoplasm of individual NBs in each brain were measured, and the normalised Spd2 signal intensities in individual NBs were presented as scattered dot plots (see Materials and Methods for detail). The lines indicate means ± SD. The numbers of NBs (n) and the numbers of brains analysed (N) are control: n= 29 (N = 6), Spd2WT-RES: n = 30 (N = 4), fzrRNA: n = 30 (N = 6), and Spd2WT-OE: n = 27 (N = 10). P values were calculated using non-parametric two-tailed Mann-Whitney tests. Based on these results, the relative centrosomal Spd2 protein levels in NBs can be estimated as wildtype (or control) : Spd2WT-RES: fzrRNAi: Spd2DK-RES: Spd2WT-OE: Spd2DK-OE ­= 1: 1.00~1.18: 1.06~1.29: 2.08~2.45 (= 1.00~1.18 x 2.08): 1.93~3.62: 3.94 ~ 7.38 (= 1.93~3.62 x 2.04",
    "ncbi_link": "RES: 
fzr: 45922
Spd2: 39850"
  },
  {
    "caption": "(C) In time lapse movies, NBs that showed an active centrosome that was attached to the cortex ("Attached") and NBs with both two centrosomes being inactivated and detached from the cortex ("Detached") in interphase were counted in third instar larval brains of the indicated fly lines and their proportions are presented in bar graphs. The numbers of NBs analysed from at least four brains (n) are Control: 29, fzrRNAi: 80, Spd2WT-RES: 45, Spd2DK-RES: 52, Spd2WT-OE: 43, Spd2DK-OE: 40, Spd2WT-OE + fzrRNAi: 72. p-values are fzrRNAi: 0.0069, Spd2WT-RES: 0.2479, Spd2DK-RES: 0.0116, Spd2WT-OE: <0.0001, Spd2DK-OE: <0.0001, Spd2WT-OE + fzrRNAi: 0.0008 (Pearson's chi-squared tests were performed between control and each condition).",
    "ncbi_link": "RES: 
fzr: 45922
Spd2: 39850"
  },
  {
    "caption": "(E) The signal intensities of the indicated centriolar and PCM proteins at two centrosomes were quantified in individual interphase NBs in Spd2WT-RES and Spd2DK-RES larval brains, and their asymmetric distributions of their centrosomal signals between the two centrosomes are presented as Asymmetric Indexes (see Materials and Method) in a scatted dot plot. Red bars represent means ± SD. The numbers of NBs analysed from at least 3 different brains of Spd2WT-RES and Spd2DK-RES (n) were 40 and 40 for Asl, 40 and 41 for RFP-Spd2, 42 and 37 for Cnn, 40 and 41 for γTub, and 40 and 40 for AurA.",
    "ncbi_link": "RES: 
Spd2: 39850"
  },
  {
    "caption": "(D) Division axis deviations were separately analysed in NBs with apically attached interphase centrosomes ("attached") and those with centrosomes being detached from the cortex ("detached") for each line, using the same dataset as in Fig. 3C. The same control data as in Fig. 3C is shown for reference. fzrRNA detached (mean ± SD: 34.62° ± 23.39), Spd2DK-OE detached (64.01° ± 33.93), and Spd2WT-OE+fzrRNAi attached (39.55° ± 27.08) and detached (59.08° ± 34.88) brains showed statistically significant differences from control, while NBs with cortically attached centrosomes in any of the lines did not show significant differences. n: the number of NB divisions analysed from at least four brains for each line. p-values were calculated using Mann-Whitney U tests comparing with control and are shown above the dots.",
    "ncbi_link": "fzr: 45922
Spd2: 39850"
  },
  {
    "caption": "(B) Selected images from time-lapse microscopy of NBs in control (wor>mCh-Tub, pUbq-GFP-Fzr, top panels) and Spd2DK-OE (lower panels) larval brains (Movies EV1, EV10). In the control NB, the daughter centrosomes (blue arrowheads) first matured (-5.0 min) and was segregated into the daughter NB (12.0 min), while the mother centrosome (yellow arrowheads) matured a little later (0.0 min) and segregated into the GMC. In contrast, in the Spd2DK-OE NB, both centrosomes lost microtubule nucleation activity in interphase (red arrowheads). The centrosome that matured earlier (blue arrowheads, -6.0 min) was incorrectly segregated into the GMC (12.0 min) while the centrosome that matured later (yellow arrowheads, 0.0 min) was segregated into the NB (12.0 min). Dotted white lines outline the dividing NBs and the newly formed GMC, which are also marked by asterisks.",
    "ncbi_link": "GFP: 
mCh: 
Ubq: 
Fzr: 45922
Spd2: 39850
Tub: 7846
wor: 34906"
  },
  {
    "caption": "(C, D) Representative images of interphase NBs in fixed wor>lacZ (control, top panels) and HA-Spd2WT-OE larval brains expressing Polo-GFP from the native promoter and stained for DAPI and Spd2 (C). Asymmetric indexes of Polo-GFP in interphase NBs wor>lacZ (control, top panels) and HA-Spd2WT-OE larval brains (D). 38 and 39 NBs (n) from at least three brains were analysed in each line. The asymmetric distribution of Polo-GFP at interphase centrosomes was unaffected by HA-Spd2WT overexpression.",
    "ncbi_link": "HA: 
lacZ: 945006
Spd2: 39850
wor: 34906"
  },
  {
    "caption": "(E) Representative images of interphase NBs in fixed mCh-Spd2WT-RES (top panels) and mCH-Spd2DK-RES larval brains and stained for DAPI, γTub and Cnn. Both multichannel and single-channel images of mCh-Spd2, γTub and Cnn are shown. Dotted yellow squares highlight centrosomes and their magnified images are shown in insets. Similar to Spd2DK-RES NBs, in mCh-Spd2CONS-RES NBs, Spd2 and γTub were more symmetrically accumulated at the two centrosomes than in mCh-Spd2WT-RES NBs, but Cnn was still asymmetrically distributed.",
    "ncbi_link": "mCh: 
mCH: 
RES: 
Spd2: 39850"
  },
  {
    "caption": "(G, H) FRAP analyses of the centrosomal Spd2 fluorescent signals in Spd2WT-RES and Spd2DK-OE NBs. (G) Representative images from time-lapse movies (Movies EV13, EV14) of Spd2 fluorescent signals in Spd2WT-RES NBs (top panels) and Spd2DK-OE NBs (lower panels) upon photobleaching. (H) The recoveries of the fluorescent intensities of centrosomal Spd2 signals after photobleaching were measured in Spd2WT-RES (n = 7) and Spd2DK-OE NBs (n = 5). Means ± SEM of the normalised fluorescent intensities are shown in a line graph. Centrosomal Spd2 signals recovered more fully after photobleaching in Spd2DK-OE NBs than in Spd2WT-RES NBs.",
    "ncbi_link": "RES: 
Spd2: 39850"
  },
  {
    "caption": "(B) Kaplan-Meier survival curves for colon cancer patients with or without dysfunction of iron homeostasis in the GSE dataset (n = 590 samples, P = 0.016, Log-rank (Mantel-Cox) test). \"Normal\" represents the patients with unaltered expression of iron homoeostasis-related genes, including LTF, CP, FTH1, SLC30A1 and TFRC; \"Dysfunctional iron homoeostasis\" represents the patients with altered expression of iron homoeostasis-related genes.",
    "ncbi_link": "CP: 1356
FTH1: 2495
LTF: 4057
SLC30A1: 7779
TFRC: 7037"
  },
  {
    "caption": " (E) Mass spectrum analysis of IREB2-associated proteins. Mock or IREB2-FLAG was transfected into HEK293T cells and FLAG-tagged proteins were enriched by anti-FLAG M2 beads and incubated with lysates from normal mice colon tissues. Five matched peptides corresponding to OTUD1 were shown on the right panel. ",
    "ncbi_link": "FLAG: 
IREB2: 3658"
  },
  {
    "caption": " (G) Half-life analysis of IREB2 in wild-type (WT) and OTUD1─/─ NCM460 cells. Cells were treated with 100 μg/ml cycloheximide (CHX) and collected at the indicated times for western blot analysis (Up), the relative protein level of IREB2 was assessed by ImageJ software (Down) (n = 3 biological replicates, mean ± s.e.m., **P = 0.0049, ***P < 0.0001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (H) Flow cytometric analysis of TFRC expression in mock and OTUD1 expressing CT26 cells with AFC (50 μM) and Hemin (100 μM) treatment. MFI, mean fluorescence intensity. Control uses isotype-matched control antibody (n = 4 biological replicates, mean ± s.e.m., **P = 0.0010, ***P = 0.0008, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (I) Flow cytometric analysis of TFRC expression in wild-type (WT) and OTUD1─/─ NCM460 cells with DFO (100 μM) treatment. MFI, mean fluorescence intensity. (n = 4 biological replicates, mean ± s.e.m., ***P = 0.0001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (A) RT-qPCR analysis of OTUD1 mRNA levels in colon tumors and matched adjacent normal tissues (n = 101 human samples, ***P < 0.001, two-tailed paired Student's t-test) ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (B) Correlation of mRNA expression of TFRC and OTUD1 in colorectal cancer (n = 101 human samples, two-tailed Pearson correlation analysis, ****P < 0.0001). ",
    "ncbi_link": "OTUD1: 220213
TFRC: 7037"
  },
  {
    "caption": " Intracellular iron concentration was measured in CT26 cells stably expressing mock, OTUD1 or OTUD1C320S (n = 2 biological replicates) ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " Intracellular iron concentration was measured in wild-type (WT) or OTUD1─/─ NCM460 cells (n = 4 biological replicates, mean ± s.e.m., ***P < 0.001, two-tailed unpaired Student's t-test) ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (C) The protein levels of IREB2, TFRC and OTUD1 were assessed by western blot in colon tissues from wild-type (WT) or Otud1─/─ mice. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " (D) Intracellular iron concentration was measured in colon tissues from wild-type (WT) or Otud1─/─ mice with supplementation of ferrous gluconate (n = 3 biological replicates, mean ± s.e.m., ***P = 0.0007, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " Mean corpuscular volume (MCV) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), *P = 0.0472, two-tailed unpaired Student's t-test) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " mean corpuscular hemoglobin (MCH) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P = 0.0048, two-tailed unpaired Student's t-test) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " mean corpuscular hemoglobin concentration (MCHC) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P = 0.0068, two-tailed unpaired Student's t-test) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " , red boold cells (RBCs) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P = 0.0049, two-tailed unpaired Student's t-test) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " hemoglobin (HB) (n = 5 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P = 0.0036, ***P = 0.0002, two-tailed unpaired Student's t-test) (I) in wild-type (WT) and Otud1─/─ mice with or without low-iron diets for indicated times. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " (A-B) Macroscopic evaluation (A) and tumor volume (mock, n = 7 biological replicates; OTUD1, n = 9 biological replicates; OTUD1C320S, n = 9 biological replicates; mean ± s.e.m., ***P < 0.001, two-tailed unpaired Student's t-test) (B) of mock, OTUD1 and OTUD1C320S expressing CT26 tumors in BALB/c mice. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " Macroscopic evaluation of mock and OTUD1 expressing LLC tumors in C57BL/6 mice. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " tumor volume (n=6 biological replicates, mean ± s.e.m., **P < 0.01, ***P = 0.0007, two-tailed unpaired Student's t-test) of mock and OTUD1 expressing LLC tumors in C57BL/6 mice. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " survival analysis (n=5 biological replicates, **P = 0.0021, Log-rank (Mantel-Cox) test) of mock and OTUD1 expressing LLC tumors in C57BL/6 mice. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (G) Flow cytometric analysis of TFRC expression in mock (n = 4 biological replicates), OTUD1 (n = 6 biological replicates) and OTUD1C320S (n = 5 biological replicates) expressing CT26 tumors. MFI, mean fluorescence intensity (mean ± s.e.m., **P < 0.01, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (H) Flow cytometric analysis of TFRC expression in mock or OTUD1 expressing LLC tumors. MFI, mean fluorescence intensity. (n = 5 biological replicates, mean ± s.e.m., **P = 0.0011, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (I) Iron concentration of mock, OTUD1 and OTUD1C320S tumors was assessed by Inductively Coupled Plasma Mass Spectrometry (n = 3 biological replicates, mean ± s.e.m., *P = 0.0237, **P = 0.0098, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (J)Analysis of tumor infiltrating CD8+ T cells or CD4+ T cells in mock (n = 4 biological replicates), OTUD1 (n = 6 biological replicates) and OTUD1C320S (n = 5 biological replicates) expressing CT26 tumors in BALB/c mice (mean ± s.e.m., **P < 0.01, ***P < 0.001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " Flow cytometric analysis of CD8+ T cells, CD4+ T cells (n = 6 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), ***P = 0.0003, two-tailed unpaired Student's t-test) isolated from mock and OTUD1 overexpressing LLC tumors. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " PD-1 expression in T cells (n = 6 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), ***P < 0.0001, two-tailed unpaired Student's t-test) isolated from mock and OTUD1 overexpressing LLC tumors. MFI, mean fluorescence intensity. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " A) Quantitative proteomics study of wild-type (WT) and OTUD1─/─ NCM460 cells. The expression of TFRC and IREB2 were highlighted with red color. Intensity indicates label-free quantification (LFQ) intensity of proteins in mass spectrometry. ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (B) Wild-type (WT) and OTUD1─/─ NCM460 cells were treated with indicated concentration of H2O2 for 24 hours and cell viability was measured by PI staining (n = 3 biological replicates, mean ± s.e.m., *P < 0.05, **P < 0.01, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (C) CT26 cells stably expressing mock or OTUD1 were treated with 200 μM H2O2 together with various cell death inhibitors containing Fer-1 (10 μM), Z-VAD (25 μM) and nec-1 (20 μM). Cell viability was measured by PI staining n = 3 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), *P = 0.0119, **P = 0.0015, ***P < 0.001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (D) CT26 cells stably expressing mock, OTUD1 or OTUD1C320S were treated with Erastin (10 μM) and RSL3 (5 μM), and cell viability was measured by PI staining (n = 3 biological replicates, mean ± s.e.m., ns, not significant (P > 0.05), **P < 0.01, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (E) Wild-type (WT) and OTUD1─/─ NCM460 cells were treated with Erastin (10 μM) and RSL3 (5 μM) for 24 hours and cell viability was measured by PI staining (n = 3 biological replicates, mean ± s.e.m., **P = 0.0082, ***P < 0.001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " F) Intracellular ROS levels in mock, OTUD1 and OTUD1C320S overexpressing CT26 cells treated with Erastin (10 μM), AFC (50 μM) or H2O2 (100 μM) were detected by DCFDA staining. MFI, mean fluorescence intensity (n = 2 biological replicates). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (G) Intracellular ROS levels in mock (n = 4 biological replicates), OTUD1 (n = 6 biological replicates) or OTUD1C320S (n = 5 biological replicates) expressing CT26 tumors (mean ± s.e.m., *P = 0.0189, **P = 0.0086, two-tailed unpaired Student's t-test) were detected by DCFDA staining. MFI, mean fluorescence intensity. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (I) Tumor volume (mock, n = 4 biological replicates; mock + NP-VE, n = 6 biological replicates; OTUD1, n = 4 biological replicates; OTUD1 + NP-VE, n = 6 biological replicates ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " Flow cytometric analysis of DCFDA (n = 4 biological replicates, mean ± s.e.m., ***P < 0.001, two-tailed unpaired Student's t-test) of mock or OTUD1 expressing CT26 tumors treated with or without NP-VE. MFI, mean fluorescence intensity. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " Flow cytometric analysis of the percentage of tumor infiltrating CD8+ T cells (n = 4 biological replicates, mean ± s.e.m., *P = 0.0433, ***P = 0.0001, two-tailed unpaired Student's t-test) of mock or OTUD1 expressing CT26 tumors treated with or without NP-VE. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " CT26 cells stably expressing mock or OTUD1 were treated with 5 μM RSL3, and medium was collected to measure ATP level (n = 4 biological replicates, mean ± s.e.m., ***P < 0.0001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " wild-type (WT) or OTUD1─/─ NCM460 cells were treated with 5 μM RSL3, and medium was collected to measure ATP level (n = 4 biological replicates, mean ± s.e.m., ***P < 0.0001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 220213"
  },
  {
    "caption": " (C) Volcano plots of genes differentially expressed in tumor interstitial fluid (TIF) of mock and OTUD1 expressing CT26 tumors. Left, example of genes downregulated in OTUD1 overexpressing tumor interstitial fluid; right, example of genes upregulated in OTUD1 overexpressing tumor interstitial fluid. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (D) Immunoblot analysis of protein levels of HMGB1, HSP70 and HSP90 in tumor interstitial fluid of mock, OTUD1 and OTUD1C320S expressing CT26 tumors. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (E) ATP level in tumor interstitial fluid (TIF) of mock or OTUD1 overexpressing CT26 cells (n = 5 mice, mean ± s.e.m., ***P < 0.001, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (F and G) BALB/c mice were immunized with 1×106 OTUD1 expressing or mock CT26 cells in the left flank and challenged with 2×106 wild-type CT26 cells in the right flank 10 days later. Macroscopic evaluation (F) and tumor volume (n=7 mice, mean ± s.e.m., **P = 0.0053, two-tailed unpaired Student's t-test) (G) of tumors in the right flank were shown. ",
    "ncbi_link": "OTUD1: 71198"
  },
  {
    "caption": " (E) Flow cytometric analysis of TFRC expression in intestinal epithelial cells (IECs) from wild-type (WT) and Otud1─/─ mice treated with AOM/DSS. MFI, mean fluorescence intensity. (n = 4 biological replicates, mean ± s.e.m., **P = 0.0062, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " (F) GSEA of genes expressed in colon tissues from wild-type (WT) and Otud1─/─ mice treated with AOM/DSS (n = 3 biological replicates). ES, enrichment score; NES, normalized enrichment score. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " (H) Flow cytometric analysis of various T cell subsets in lamina propria mononuclear cells (LPMC) isolated from wild-type (WT) and Otud1─/─ mice treated with AOM/DSS (n = 5 biological replicates, mean ± s.e.m., **P = 0.0025, ***P = 0.0005, two-tailed unpaired Student's t-test). ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": " (I) Intracellular ROS levels in colon tissues from wild-type (WT) or Otud1─/─ mice treated with AOM/DSS (n = 4 biological replicates, mean ± s.e.m., **P = 0.0072, two-tailed unpaired Student's t-test) were detected by DCFDA staining. MFI, mean fluorescence intensity. ",
    "ncbi_link": "Otud1: 71198"
  },
  {
    "caption": "(A) After 4 h of starvation in 1% K‐acetate medium in the presence of PMSF, autophagic vesicles can be visualized in vacuoles of wild‐type and pep4prb1 cells using Normaski optics. In aut2Δ and aut7Δ cells no autophagic vesicles can be seen. Bar represents 20 μm.",
    "ncbi_link": "aut2: 855498
aut7: 852200
pep4: 855949
prb1: 856649"
  },
  {
    "caption": "(B) Total protein breakdown of cells starved on nitrogen‐free medium is significantly reduced in aut2Δ and aut7Δ cells compared with wild‐type cells. pep4Δ (pra1Δ) cells are almost completely impaired in starvation‐induced vacuolar protein breakdown. Cells were pulse‐labeled with [35S]methionine and chased on non‐radioactive starvation medium. Aliquots were taken at the indicated times and acid soluble small peptides generated by proteolysis were determined according to Straub et al. (1997).",
    "ncbi_link": "aut2: 855498
aut7: 852200
pep4: 855949
pra1: 855949"
  },
  {
    "caption": "(C) Survival during starvation. Like pep4Δ (pra1Δ) cells, which are almost completely impaired in vacuolar proteolysis, aut2Δ and aut7Δ cells exhibit a significantly reduced survival rate during starvation on nitrogen‐free medium as compared with wild‐type cells. Aliquots of cells incubated in 1% K‐acetate were plated and growing colonies were determined according to Straub et al. (1997).",
    "ncbi_link": "aut2: 855498
aut7: 852200
pep4: 855949
pra1: 855949"
  },
  {
    "caption": "Maturation of proaminopeptidase I is impaired in aut2‐1 (A), aut2Δ (B) and aut7Δ (C) cells. Further details are outlined in the text. Crude extracts were prepared from cells starved 4 h on 1% K‐acetate.",
    "ncbi_link": "aut2‐1: 855498
aut2: 855498
aut7: 852200"
  },
  {
    "caption": "Maturation of proaminopeptidase I is impaired in aut2‐1 (A), aut2Δ (B) and aut7Δ (C) cells. Further details are outlined in the text. Crude extracts were prepared from cells starved 4 h on 1% K‐acetate.",
    "ncbi_link": "aut2: 855498
aut7: 852200"
  },
  {
    "caption": "Maturation of proaminopeptidase I is impaired in aut2‐1 (A), aut2Δ (B) and aut7Δ (C) cells. Further details are outlined in the text. Crude extracts were prepared from cells starved 4 h on 1% K‐acetate.",
    "ncbi_link": "aut2: 855498
aut7: 852200"
  },
  {
    "caption": "(A) Detection of protein-protein interactions using the two‐hybrid system. Intense staining indicates an interaction between Aut2p and Aut7p, Aut2p and Tub1p, and Aut2p and Tub2p. AUT7, TUB1 and TUB2 are cloned in‐frame with the GAL4‐activator domain. AUT2 and AUT7 were fused to the GAL4‐binding domain (see Materials and methods).",
    "ncbi_link": "GAL4: "
  },
  {
    "caption": "(B) Affinity chromatography confirms protein-protein interaction between Aut2p and Aut7p. A fusion protein of Aut2p with the 26 kDa glutathione‐S‐transferase (GST) domain from Schistosoma japonicum (see Materials and methods) was bound to glutathione-Sepharose 4B. This GST-Aut2p column was incubated with a crude extract from aut7Δ cen Met25::AUT7-GFP cells. The non‐bound supernatant (S) fraction (lane 1) was taken away. Gel beads were successively washed with NaCl solutions of increasing concentrations to remove non‐specifically bound proteins. After the final 500 mM NaCl wash (W, lane 2), bound proteins were eluted with Laemmli buffer (E, lane 3). Samples were analyzed in immunoblots with monoclonal antibodies directed against GFP. Using Aut2p-GST, a clear band corresponding to Aut7p-GFP is seen in the eluate fraction (lane 3, arrowhead). As a control, GST alone was attached to the column and no band was detectable (lane 6).",
    "ncbi_link": "AUT7: 852200
aut7: 852200
Met25: 851010"
  },
  {
    "caption": "Benomyl sensitivity of wild‐type cells overexpressing AUT2 and AUT7, and of aut2Δ and aut7Δ cells is not altered. Cells were grown to stationary phase and dilution series with decreasing cell densites were dropped on CM plates without uracil containing 15 and 30 μg/ml benomyl. Plates were incubated at 30°C.",
    "ncbi_link": "AUT2: 855498
aut2: 855498
AUT7: 852200
aut7: 852200"
  },
  {
    "caption": "(A) Autophagosome‐like vesicles (arrowhead) are accumulating in the cytoplasm of aut2Δ cells starved for 4 h on 1% K‐acetate in the presence of PMSF. Bar represents 100 nm.",
    "ncbi_link": "aut2: 855498"
  },
  {
    "caption": "(B) Electron micrographs unravels the accumulation of double membrane‐layered autophagosome‐like vesicles in the cytoplasm of aut7Δ cells starved for 3 h in nitrogen‐free medium in the presence of PMSF. Arrowheads indicate the clearly distinguishable two membrane layers. Bar represents 100 nm.",
    "ncbi_link": "aut7: 852200"
  },
  {
    "caption": "(C and D) Cytosol containing autophagosome‐like vesicles accumulating in the cytosol of aut2Δ cells (D) can be isolated with an additional 100 000 g centrifugation step yielding a P100 pellet fraction. In wild‐type cells (C), no P100 is detectable. Fatty acid synthase (Fas) was used as a cytosolic protein. Further details are given in the text.",
    "ncbi_link": "aut2: 855498"
  },
  {
    "caption": "(a) HACE1 mRNA expression is markedly increased in ischaemic and dilated cardiomyopathy (ICM and DCM) heart failure (HF) patient heart tissue compared with non-failing hearts (NF). Expression levels were normalized to HPRT and GAPDH mRNAs. n=15 per group. Control, non-failing heart.",
    "ncbi_link": "GAPDH: 
HPRT: 
HACE1: 57531"
  },
  {
    "caption": "(b) Elevated Hace1 mRNA expression in sTAC mousehearts compared with sham controls, expression levels were normalized to Hprt and Gapdh mRNAs. n=6-9 per group, P=0.004 (unpaired two-tailed Student's t-tests).",
    "ncbi_link": "Gapdh: 
Hprt: 
Hace1: 209462"
  },
  {
    "caption": "(c-e) Hace1−/− and WT mice were subjected to sTAC or sham surgery and analysed 4 days after the operation. Echocardiography measurement of (c) LV fractional shortening (FS=(LVEDD−LVESD)/LVEDD × 100%); (d) LV end-diastolic dimension (LVEDD) (mm) and (e) LV end-systolic dimension (LVESD) (mm) are shown. n=6-8 for each group.",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(f) Mortality rate of WT and Hace1−/− mice after sTAC is shown by Kaplan-Meier plots as the survival proportion of each cohort of mice. Survival incidence in mice over the indicated follow-up period is shown as the ratio of the number of mice survived/total mice analysed for each group. This represents 60% (12/20) for Hace1−/− sTAC mice, 84% (16/19) for Hace1+/+ sTAC mice and 100% (12/12) for both Hace1−/− and Hace1+/+ sham mice on day 4; P value as indicated (log-rank χ2-test).",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(g) Heart weight/body weight ratios (HW/BW) and (h) lung weight/body weight ratio (LW/BW) of WT and Hace1−/− mice 4 days after sTAC or sham surgery. n=15-21 for each group.",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(j) Real-time RT-PCR analyses reveal a significant increase in the expression of the atrial natriuretic peptide gene (Nppa), a clinical biomarker for heart hypertrophy, in Hace1−/− sTAC heart; expression levels were normalized to Hprt and Gapdh mRNAs. n=6-9 per group. In all panels, error bars represent s.e.m., one-way analysis of variance were used to calculate P-values.",
    "ncbi_link": "Gapdh: 
Hprt: 
Hace1: 209462
Nppa: 230899"
  },
  {
    "caption": "Representative immunohistochemistry staining for (a) ubiquitinated protein (brown); (b) p62 (brown) and (c) GFP-LC3 (brown) in paraffin sections of heart revealing increased accumulation of p62, ubiquitinated protein and LC3 in Hace1−/− sTAChearts. Hearts from three mice in each group were analysed (scale bars, 10 μm).",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(i) Increased Ub proteasome activity in Hace1−/− sTAC hearts as measured by 20S proteasome activity assay (n=4-6 per group). In all panels, error bars represent s.e.m., P value between KO and WT sTAC as indicated (one-way analysis of variance).",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(a) Representative confocal microscopy images showing HACE1 (green) localizing to the Ub+ protein aggregates (red) induced by puromycin treatment in HA-HACE1 MEF. Arrows indicate co-localized puncta. Scale bar, 10 μm.",
    "ncbi_link": "HACE1: 209462"
  },
  {
    "caption": "(b) Representative confocal micrographs of Hace1−/− and Hace1+/+ NCM treated with puromycin for 4 h (puromycin), puromycin followed by 8 h recover (puromycin+recover). Vehicle (PBS)-treated cells were used as control. Hace1 deficiency in cardiomyocytes (Hace1−/− NCM) blocks ubiquitinated protein aggregate degradation. Scale bars, 10 μm.",
    "ncbi_link": "Hace1: 209462"
  },
  {
    "caption": "(c,d) WT and Hace1−/− MEF as well as Hace1−/− MEF stably transfected with WT HACE1 and C876S-mutant HACE1were subjected to protein aggregates clearance assay by pulsing with puromycin for 4 h to induce protein aggregate formation followed by an 8-h chase to monitor for aggregate clearance. Cells were fixed and stained for ubiquitinated proteins to visualize aggregates. Vehicle (PBS)-treated MEFs were used as control. (c) Representative confocal micrographs of images used for quantification of the efficiency of aggregates clearance in d (percentage of cells that cleared all aggregates by 8 h after puromycin removal). At least 10 images from each group were used for the calculation, error bars represent s.e.m., P0.001 (one-way analysis of variance). Scale bars, 10 μm.",
    "ncbi_link": "HACE1: 209462
Hace1: 209462"
  },
  {
    "caption": "(a) Diagrams representing GFP-tagged WT HACE1 and mutant HACE1 (HACE1Δ HECT and HACE1Δ ANK) constructs transiently transfected into Hace1−/− MEF for protein aggregate clearance assay. (b-d) Representative confocal micrographs of (b) WT, (c) ΔHECT and (d) ΔANK MEF subjected to protein aggregate clearance assay by pulsing with puromycin for 4 h to induce protein aggregate formation followed by an 8-h chase to monitor for aggregate clearance. Vehicle-treated MEFs were used as control. Scale bars, 10 μm.",
    "ncbi_link": "HACE1: 209462"
  },
  {
    "caption": "(a) Fluorescence microscopy images showing HACE1 (green) co-aggregating with p62 (red) in the perinuclear space on puromycin treatment (8 h) in Hace1−/− NCM transiently expressing HACE1-GFP. p62 was visualized by immunofluorescent staining. Arrows indicate co-localized puncta.",
    "ncbi_link": "Hace1: 209462
HACE1: 209462"
  },
  {
    "caption": "(b) Representative confocal images showing HACE1 (red) localizes to LC3+ puncta (green) induced by MG132 treatment (8 h) in Hace1−/−GFP-Lc3Tg NCM cells transiently expressing HACE1-RFP. Arrows indicate co-localized puncta.",
    "ncbi_link": "Hace1: 209462
Lc3: 67443///66734"
  },
  {
    "caption": "(c) Primary NCMs from Hace1+/+Lc3Tg and Hace1−/−Lc3Tg newborn pups were treated with or without MG132 for 8 h and the cell lysates were subjected to western blot with anti-GFP antibodies. Gapdh was used as a loading control.",
    "ncbi_link": "Hace1: 209462
Lc3: 67443///66734"
  },
  {
    "caption": "(d) Fluorescence microscopy images showing co-localization of HACE1 (green) with Lamp1 (red) on MG132 treatment (8 h) in Hace1−/−NCM cells transiently expressing HACE1-GFP. Lamp1 was visualized by immunofluorescent staining. Scale bar, 10 μm in all images.",
    "ncbi_link": "Hace1: 209462
HACE1: 209462"
  },
  {
    "caption": "(a,b) Primary NCMs from WT and Hace1−/− newborn pups stably transfected with WT HACE1 and C876S-mutant HACE1, were transiently transfected with a tandem tagged mRFP-GFP-LC3 reporter (tfLC3) plasmid, followed by 8 h treatment with MG132 or MG132 plus Baf in the last 4 h, and were subjected to confocal microscopy. DMSO treatment only was used in the control group. (a,c) Representative confocal micrographs of images used for quantification of the percentage of yellow dots in b and d. At least 10 images from each group were used for the calculation; error bars represent s.e.m., P-value as indicated (one-way ANAVO). Scale bars, 10 μm. Autophagosomes show both GFP and mRFP-LC3 signals (yellow) while autolysosomes exhibit mRFP-L3 signals only (red).",
    "ncbi_link": "Hace1: 209462
HACE1: 209462
LC3: Q91VR7///Q9CQV6///67443///66734
LC3: 67443///66734"
  },
  {
    "caption": "(c,d) WT and Hace1−/− MEF, as well as Hace1−/− MEF stably transfected with WT HACE1 and C876S-mutant HACE1, were transiently transfected with a tandem tagged mRFP-GFP-LC3 reporter (tfLC3) plasmid, followed by 8 h treatment with MG132 or MG132 plus Baf in the last 4 h, and were subjected to confocal microscopy. DMSO treatment only was used in the control group. (a,c) Representative confocal micrographs of images used for quantification of the percentage of yellow dots in b and d. At least 10 images from each group were used for the calculation; error bars represent s.e.m., P-value as indicated (one-way ANAVO). Scale bars, 10 μm. Autophagosomes show both GFP and mRFP-LC3 signals (yellow) while autolysosomes exhibit mRFP-L3 signals only (red).",
    "ncbi_link": "Hace1: 209462
HACE1: 209462
LC3: 67443///66734"
  },
  {
    "caption": "(a,b) Hace1−/− MEF cells were stably transfected with HA-tagged WT HACE1 (HA-HACE1) and empty vector MSCV. (a) Immunoblot for HA shows stable expression of HA-tagged HACE1 in HA-HACE1MEF cell lysate. (b) HA-HACE1MEF and control MSCVMEF cell lysates were subjected to Co-IP with anti-HA antibody and coomassie blue staining shows a couple of distinct bands only detected in HA-HACE1MEFIP pull-down as indicated by red arrows.",
    "ncbi_link": "MSCV: 
HACE1: 209462"
  },
  {
    "caption": "(c-f) Identification of HACE1 interacting proteins by MS analysis of Co-IP products. (c) Hierarchical clustering (heat) map demonstrating the clustering of proteins based on their expression intensities in HA-HACE1MEF and control MSCVMEFHA-IP pull-down products. To the left of the heat map, selected annotations found to be enriched in the protein clusters are shown. n=5 for HA-HACE1 group and n=4 for control MSCV group. (d) Pie chart shows enriched representative HACE1-interacting proteins according to molecular function by GO term. (e) Selected HACE1-interacting proteins identified by HA-IP MS were evaluated by western blot with the indicated antibodies (IB). HA-HACE1 denotes HA-IP pull-down from HA-HACE1MEF; MSCV denotes HA-IP pull-down from control MSCVMEF; and input indicates HA-HACE1MEF lysate before IP. (f) HA-HACE1MEF and control MSCVMEF lysates were subjected to co-IP with an anti-Unc-45b antibody and the pull-down were analysed by western blot with an anti-HA antibody.",
    "ncbi_link": "MSCV: 
HACE1: 209462"
  },
  {
    "caption": "(g,h) HA-IP pull-down products from HA-HACE1MEF (HA-HACE1) and Hace1 KO MSCVMEF (MSCV) immortalized in HA beads were further subjected to Co-Co-IP with WT mouseheart lysates, and the pull-down products were analysed by western blot using the indicated antibodies. HACE1 and those proteins with which it interacts were still detectable (g). There were also increased ubiquitinated proteins in the Co-Co-IPheart tissues (h).",
    "ncbi_link": "MSCV: 
HACE1: 209462"
  },
  {
    "caption": "(a-c) Representative western blots and (d) quantification show increased accumulation of some of the HACE1-interacting proteins in the Hace1−/− sTAC myocardium. n=3 mice per group, error bars represent s.e.m., P-value between KO and WT sTAC as indicated (one-way analysis of variance). Gapdh was used as a loading control.",
    "ncbi_link": "HACE1: 209462
Hace1: 209462"
  },
  {
    "caption": " C mRNA expression in female Lin-Sca1+ cells, differentiated in the presence of 100 nM Rosi or vehicle for 8 days, as determined by qRT-PCR (n=3) t-test Cited4-/- vs. Cited4+/+ (Rosi) *P=0.013 (Ucp1), **P=0.004 (Cpt1b), *P=0.026 (Dio2)",
    "ncbi_link": "Cited4: 56222
Cpt1b: 12895
Dio2: 13371
Ucp1: 22227"
  },
  {
    "caption": " G mRNA expression in primary SVF cells from human female subcutaneous fat transfected with the indicated siRNA prior to differentiation in the presence of 100 nM Rosi for 9 days, as determined by qRT-PCR (n=3) ***P=0.0002 (CITED4), **P=0.002 (UCP1), *P=0.02 (UCP1), *P=0.035/0.026 (PPARG), ***P=0.0006 (SLC2A4), **P=0.002 (ADIPOQ) in one-way ANOVA with Tukey posttests (vs. siCtrl)",
    "ncbi_link": "ADIPOQ: 9370
CITED4: 163732
PPARG: 5468
SLC2A4: 6517
UCP1: 7350"
  },
  {
    "caption": " A-C Quantitative fluorescence microscopy of LipidTOX- and DAPI-stained female Cited4F/F Lin-Sca1+ progenitor cells transfected with Cre or control mRNA prior to differentiation in the presence of 100 nM Rosi for 8 days (n=5). **P=0.002 in t-test (Cre vs. Ctrl). Scale bar is 10 µm ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " D, E Ucp1 expression in female Cited4F/F Lin-Sca1+ progenitor cells transfected with Cre or control mRNA prior to differentiation in the presence of 100 nM Rosi for 8 days, as determined by Western blot with VCP as loading control (n=3) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " A, B mRNA expression in scWAT of mice fed a diet with 0.0075% Rosi or control diet for 2.5 weeks, determined by qRT-PCR t-test Cited4-/- vs. Cited4+/+ (Rosi), (A) n=5/5/6/6, **P=0.003 (Ucp1), **P=0.008 (Cidea), **P=0.007 (Cyc1), *P=0.048 (Ndufb3), (B) n=5/4/5/5, *P=0.022 (Ucp1), *P=0.037 (Cidea)",
    "ncbi_link": "Cidea: 12683
Cited4: 56222
Cyc1: 66445
Ndufb3: 66495
Ucp1: 22227"
  },
  {
    "caption": " C, D Ucp1 expression in scWAT of mice treated as in A, as determined by Western blot with VCP as loading control t-test Cited4-/- vs. Cited4+/+ (Rosi), females: n=5/5/6/6, *P=0.011, males: n=5/4/5/5",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " E mRNA expression in scWAT of female mice treated with  CL-316,243 (CL) (1 mg/kg/day via Alzet minipumps) or vehicle for 10 days (n=5/7/13, t-test Cited4-/- vs. Cited4+/+ (CL)) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " F mRNA expression in scWAT of female mice  exposed to 5°C or 23°C for 2 weeks (n=5/10/6, t-test Cited4-/- vs. Cited4+/+ (5°C)) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " C Oxygen consumption rate of female mice fed a diet with 0.0075% Rosi for 3.5 weeks and injected with 1 mg/kg CL-316,243 (CL) at the indicated time point, as determined by indirect calorimetry (n=9/10). *P=0.013 (-1 h), *P=0.045 (3 h), *P=0.015 (5 h), *P=0.016 (6 h), *P=0.019 (8 h), *P=0.046 (10 h) in repeated measures 2x2 ANOVA with Holm-Sidak posttests (Cited4-/- vs. Cited4+/+) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " D Maximal CL-induced oxygen consumption rate of female mice shown in (C) adjusted for body weight by ANCOVA. Averages of VO2 throughout 3-8 hours post CL injection were calculated for each mouse (n=9/10). *P=0.049 in ANCOVA with Bonferroni posttest (Cited4-/- vs. Cited4+/+) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " E Oxygen consumption rate of male mice treated as in (A), determined as in (C) (n=9/10). ANCOVA with Bonferroni posttest (Cited4-/- vs. Cited4+/+) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " F Oxygen consumption rate of male mice treated as in (C), determined as in (C) (n=9/10). *P=0.044 (9 h), *P=0.013 (12 h) in repeated measures 2x2 ANOVA with Holm-Sidak posttests (Cited4-/- vs. Cited4+/+) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " G Maximal CL-induced oxygen consumption rate of male mice shown in (F) and calculated as in (D) (n=9/10). ANCOVA with Bonferroni posttest (Cited4-/- vs. Cited4+/+) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " A, B mRNA expression in scWAT of mice fed a high-fat diet (HFD) for 11 weeks followed by 5 weeks of HFD with 0.0075% Rosi (qRT-PCR). t-test Cited4-/- vs. Cited4+/+, (A) n=8/7, *P=0.029 (Ucp1), **P=0.009 (Elovl3), **P=0.006 (Cpt1b), **P=0.004 (Cyc1), *P=0.016 (Ndufb3), **P=0.003 (Cd36), **P=0.009 (Gyk), (B) n=7/8, *P=0.026 (Pck1) ",
    "ncbi_link": "Cd36: 12491
Cited4: 56222
Cpt1b: 12895
Cyc1: 66445
Elovl3: 12686
Gyk: 14933
Ndufb3: 66495
Pck1: 18534
Ucp1: 22227"
  },
  {
    "caption": " E, F Blood glucose during insulin tolerance test (ITT) with 1 U insulin per kg body mass on female mice after 12 weeks of HFD (n=8) (E) or 16 weeks of HFD and 4 weeks of HFD+Rosi (n=7) (F), expressed as % of the 0-time point value. **P=0.003 in repeated measures 2x2 ANOVA with Holm-Sidak posttests (Cited4-/- vs. Cited4+/+). G Area under the curve (AUC)  of blood glucose during the ITT (0-120 min) in (E,F). 2x2 ANOVA with Holm-Sidak posttests (After Rosi vs. Before Rosi) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": " H, I Blood glucose during  
insulin tolerance test (ITT) on male mice as in (E,F), n=8 (H), n=7/8 (I). Repeated measures 2x2 ANOVA with Holm-Sidak posttests (Cited4-/- vs. Cited4+/+). J Area under the curve (AUC) of blood glucose during the ITT in (H,J). **P=0.001, ***P=0.00006 in 2x2 ANOVA with Holm-Sidak posttests (After Rosi vs. Before Rosi) ",
    "ncbi_link": "Cited4: 56222"
  },
  {
    "caption": "C. qRT-PCR data showing induction of each gene in the iniBAC operon in WT Mtb cultured in low iron and in the virR mutant strain cultured in high iron, expressed as fold change relative to WT Mtb cultured in iron sufficient conditions. RNA extracted from biological triplicates was analyzed. The data are presented as means +/- SEM. **P≤ 0.01 ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "iniB: 886518
virR: 886362"
  },
  {
    "caption": "E. Protein and lipid content in vesicle preparations isolated from the same number of WT and Msm overexpressing iniACMtb (Msm iniACMtb). Three independent cultures were analyzed. Data are presented as mean ± SEM *P≤ 0.05; *** P≤ 0.001 (Student's t-test).",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "H. The graph shows the avarage of nanoparticle size distribution in three independent vesicle preparations derived from WT (black) and Msm iniACMtb (grey).",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "C. Protein in vesicle isolates derived from three independent cultures of Mtb WT and iniA::hyg mutant grown in low (LI) or high iron (HI) MM with or without 50 ng·mL-1 INH. Data are presented as mean ± SEM *P ≤ 0.05. ***P≤ 0.001 (Student's t-test)",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "D. Lipid in vesicle isolates derived from three independent cultures of Mtb WT and iniA::hyg mutant cultured in low (LI) or high iron (HI) MM with or without 50 ng·mL-1 INH. Data are presented as mean ± SD *P ≤ 0.05 (Student's t-test)",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "B. Mycobactin synthesized by Mtb WT and iniA::hyg grown in low iron conditions. Data are presented as the mean of mycobactin extracted from two independent cultures.",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "C. The Mtb siderophore synthesis mutant (ST142) was cultured in low iron MM (medium) plain or supplemented with MEV preparations derived from equal number of Mtb WT, iniA::hyg and complemented strains grown in low iron MM. ST142 growth was determined based on the number of viable cells detected by the resazurine cell viability assay. MEV obtained from three independent cultures were tested.",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "A. Representative Immunodot-blot of bacterial antigens associated with EVs isolated from the culture supernatants of THP-1 cells infected with Mtb WT, iniA:hyg and complemented strains versus uninfected cells (UI). Anti-MEV specific antiserum was used for detection. The decreasing black bar indicates that increasing dilutions were spotted onto the membrane. The experiment was repeated three times with independent cultures.",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "B. Number of nanoparticles per mL determined by Zeta View NTA in three EV preparations derived from the culture supernatans of THP-1 cells infected with Mtb WT, iniA:hyg and iniA::hyg complemented strains.",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "C. Representative Western blot of total EVs isolated from the CSF of THP-1 cells infected with Mtb WT, iniA::hyg and complemented strains versus uninfected cells (UI) detecting the exosome marker CD9. The experiment was repeated twice with similar results.",
    "ncbi_link": "iniA: 886510"
  },
  {
    "caption": "A Confocal laser scanning microscopy analyses in cells treated with BafA1. Total HA-ATZNNN (red) or HA-ATZNNN polymers (magenta) in LAMP1-positive endolysosome (green) in WT MEF. (C) Same as (A) in Cnx-KO MEF. (D) Same as (A) in WT MEF exposed to kifunensine (KIF). (E) Same as (A) in WT MEF exposed to Castanospermine (CST). (F) Same as (A) in sCNX MEF. (G) Same as (A) in Uggt1-KO MEF. ",
    "ncbi_link": "Cnx: 12330
sCNX: 12330
Uggt1: 320011"
  },
  {
    "caption": "(J) Halo-ATZNNN in Uggt1-KO MEF mock-transfected (empty pcDNA3 plasmid). (K, L) (K) Same as (J), with a plasmid for expression of active or (L) inactive UGGT1. (M) Quantification of Halo-ATZNNN-positive endolysosomes (mean, n=22, 10, 15 cells for panels J-L, respectively). One-way ANOVA and Dunnett's multiple comparison test, ns P>0.05, **** P<0.0001). ",
    "ncbi_link": "Uggt1: 320011
UGGT1: 320011"
  },
  {
    "caption": "(C) Co-immunoprecipitation of ATZXXX (Bait, lower panel) with CNX (upper panel) and BiP (middle panel). Protein content in the total cell extracts (TCE) is shown. (D) Quantification of (C) for CNX association (n=3). Unpaired two-tailed t-test, ** P<0.01*** P<0.001, **** P<0.0001. (E) Quantification of (C) for BiP association (n=3 for ATZNNN and ATZQQN; n=4 for ATZQNQ and ATZQQQ). Unpaired two-tailed t-test, * P<0.005, ** P<0.01, *** P<0.001, **** P<0.0001. ",
    "ncbi_link": "ATZ: 20703"
  },
  {
    "caption": "(C) NSI mice  homozygous for the Fah  knockout displayed a lethal neonatal phenotype (left). Fah  expression  was detected in the livers  of homozygous NSI mice  with Fah  knockout and Fah  intact NSI mice  by  Western blotting (right). Cropped blots  are shown",
    "ncbi_link": "Fah: 14085"
  },
  {
    "caption": "(F) Representative PCR amplification of MYC, TP53R249S, KRASG12D, NRASG12D, CTNNB1S45F, BRAFV600E, AXIN1G652S, IL6, PIK3CAE542K and CSF1RY969C in the genomic DNA of dissected primary tumors harvested from NSIF mice  transplanted with OC-PHHs  (Tumor) and their corresponding overexpression vector plasmids as positive controls (OCs)",
    "ncbi_link": "AXIN1: 8312
BRAF: 673
CSF1R: 1436
CTNNB1: 1499
IL6: 3569
KRAS: 3845
MYC: 4609
NRAS: 4893
PIK3CA: 5290
TP53: 7157"
  },
  {
    "caption": "(B) Genomic DNA of colonies that were derived from single cells of iHCC1-1 and iHCC2-1 tumor samples were extracted for PCR amplification of MYC, TP53R249S, and KRASG12D",
    "ncbi_link": "KRAS: 3845
MYC: 4609
TP53: 7157"
  },
  {
    "caption": "(B) Volcano plot of  RNA-seq data showing genes with differential expression  (1,591 upregulated and 2,243 downregulated genes, fold change≥2 and P value≤0.05) in iHCC cells compared to PHHs. TP53, KRAS, MYC, MUC1, and AFP  were highly expressed in  iHCC  cells, whereas hepatocyte  signature markers, including FOXA2, FOXA3, ATF5, HNF4A, and ALB  were highly expressed in PHHs",
    "ncbi_link": "AFP: 174
ALB: 213
ATF5: 22809
FOXA2: 3170
FOXA3: 3171
HNF4A: 3172
KRAS: 3845
MUC1: 4582
MYC: 4609
TP53: 7157"
  },
  {
    "caption": "HeLa  cells were transfected with a WT or mutant Parkin  plasmid (FLAG), shown in blue, along with reporters for either PA  or DAG  shown in green. DMSO  or 10 µM CCCP  was added for the indicated periods of time. Mitochondria  were visualized via anti-Tom20 staining  (red). (A) PA  accumulated on Parkin-positive mitochondria  after 1 hour of 10uM CCCP  treatment, with a more dramatic increase by 3hr and 18 hr. Scale bar = 25 µM, and zoom is 9x. (B) Quantification of imaging experiments shown in A and B. Bars represent mean with SEM from three biological independent experiments; two-way ANOVA analysis was performed for statistical analysis (***P<0.0001). (C) DAG  (diacylglycerol) accumulated on Parkin-positive mitochondria  after 5.5 hr of 10uM CCCP  treatment. Arrowheads and arrows point to the DAGR  concentration at the Golgi  and mitochondria, respectively. Scale bar = 25 µM, and zoom is 9x.",
    "ncbi_link": "FLAG: 
Parkin: 5071"
  },
  {
    "caption": "(B) HEK-293T  cells were transfected with Parkin-FLAG  and DAGR-YFP  followed by CCCP  treatment for indicated times. Mitochondrial  and cytosolic  fractions were purified and analyzed by Western blots by indicated antibodies. Citrate synthetase  and α-tubulin were used as a mitochondrial  and cytosolic  marker, respectively. Note that PLD2  and Parkin  levels were elevated in the mitochondrial  fraction in response to CCCP  treatment.",
    "ncbi_link": "FLAG: 
YFP: 
Parkin: 5071"
  },
  {
    "caption": "(C) Hela  cells were co-transfected with mCherry-Parkin  and the PA  reporter, followed by CCCP  treatment alone or with a PLD2  inhibitor VU 0364739 (3 µM) for 5.5 hrs. Line scan analysis (Image J software) corresponding to the line drawn in the images indicate colocalization  between the PA  reporter (green) and mitochondria  (red). Note that VU 0364739 suppressed mitochondrial PA  accumulation. Scale bar = 10 µM. (D) Quantification of the numbers of cells with the PA  reporter positive mitochondria  shown in (C). Asterisks indicate statistical significance (***P<0.001, Student's t-test) from three biological independent experiments. The bars indicate mean± SEM.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "(E) Hela  cells were transfected with a lipin1  siRNA, followed by the DAG  reporter and mCherry-Parkin, treated with CCCP  (10 µM) for 9 hrs and then subject to image analysis. Scale bar = 25 um, and zoom is 4x. Lipin 1 KD reduced mitochondrial DAGR, but not Golgi-DAGR, accumulation (arrowheads) (F) The numbers of cells with DAG-reporter positive mitochondria  shown in (E) and in Lipin-1 knockdown cells transfected with siRNA-resistant wildtype (WT) and catalytically dead (CD; D712E;D714E) mutant cDNA. Note that Lipin1  KD reduced mitochondrial DAG  accumulation, which can be significantly restored by the re-expression of WT, but not CD mutant, Lipin-1. The graph shows the means with SEM (error bars) from three biological independent experiments. Asterisks indicate statistical significance by one-way ANOVA (**P< 0.01, ***P<0.001).",
    "ncbi_link": "mCherry: 
Lipin 1: 23175
Lipin-1: 23175
Lipin-1: 14245
lipin1: 14245
Lipin1: 23175
Parkin: 5071"
  },
  {
    "caption": "(A-B) Hela  cells were transfected with a Lipin1  or control (cKD) siRNA followed by a GFP-Parkin  expression plasmid. Transfected cells were treated with CCCP  at 10 µM for 18 hrs, and subject to immuno-staining. (B) Quantification of Parkin-positive cells in (A) that have lost a majority of mitochondria  (marked by TOM20, arrows). Note that mitochondrial  clearance is reduced in Lipin-1  knockdown cells (arrowheads in (A)). Scale bar = 25 µM.",
    "ncbi_link": "GFP: 
Lipin-1: 23175
Lipin1: 23175
Parkin: 5071"
  },
  {
    "caption": "(C). Control or lipin1  knockdown Hela  cells stably expressing parkin-mCherry  were treated with DMSO  or CCCP  (10 µM for 18 hrs) and Bafilomycin A1  (1μM, lysosomal inhibitor) treatment, followed by immunoblotting  with indicated antibodies and quantified by the Image J. software. Note that lipin1  silencing suppressed CCCP-induced mitochondrial  protein degradation. Lipin-1-mediated mitochondrial DAG  production is required for mitophagosome  production.",
    "ncbi_link": "mCherry: 
Lipin-1: 23175
lipin1: 23175
parkin: 5071"
  },
  {
    "caption": "(D-F). Hela  cells were transfected with control or a Lipin1  siRNA followed by the expression plasmids of GFP-Parkin  and RFP-DAGR. Transfected cells were treated with DMSO or CCCP  at 10 µM for 9 hr, with or without further incubation with 1,2-Dipalmitoyl-sn-glycerol  (DPG) at 100 µM, as indicated. Autophagosome formation was assessed by an LC3  antibody (pseudocolored in white in single-channel and blue in the overlay images). Arrows point to DAGR concentration at the Golgi  under basal conditions. The number (E) and size (F, arbitrary unit) of LC3 vesicles  were quantified. n=4 biological replicates. The bars indicates mean± SEM. Asterisks indicate statistical significance by one-way ANOVA (*P< 0.05, **P<0.01). Scale bar = 25 µM and zoom is 5x. Note that both the number and size of LC3-vesicles  in Lipin-1 knockdown cells were much smaller than those in WT cells, and these defects were corrected by DPG  treatment.",
    "ncbi_link": "GFP: 
RFP: 
Lipin-1: 23175
Lipin1: 23175
Parkin: 5071"
  },
  {
    "caption": "(A) E3 ligase-deficient Parkin  mutants (T240R and T415N) have no effect on PA  accumulation (green) on depolarized, Parkin-positive mitochondria. The expression of WT and Parkin  mutants were determined by Immunoblotting. Scale bar = 25 µM, and zoom is 3x. (B) DAG  accumulation depends upon intact Parkin E3 ligase  activity. Scale bar = 25µm, and zoom is 3x. (C) Quantification of imaging experiments shown in (A) and (B). Bars represent mean with SEM; two-way ANOVA analysis was performed for statistical analysis(***P<0.001). n=3 biological replicates.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(D) Hela  cells were transfected with control or optineurin- and NDP52- siRNAs and expression plasmids of FLAG-Parkin  and YFP-DAGR. These cells were treated with DMSO  or 10 µM CCCP  for 5.5 hrs, as indicated. Note that OPTN/NDP52  double knockdown prevented mitochondrial YFP-DAGR accumulation. (Scale bar = 25 µM and zoom is 3x) (E) Hela OPTN/NDP52  knockdown cells were transfected with a siRNA-resistant wildtype or ubiquitin-binding deficient E478G OPTN  mutant, as indicated. The percentage of cells with mitochondrial YFP-DAGR following CCCP  treatment was quantified. Asterisks indicate statistical significance by one-way ANOVA (**P< 0.01, ***P<0.001) from three biological independent experiments. The bars indicate mean± SEM. Bottom panel: Expression of OPTN, OPTN  E478 and NDP52  was determined by immunoblotting.",
    "ncbi_link": "FLAG: 
YFP: 
NDP52: 10241
optineurin: 10133
OPTN: 10133
Parkin: 5071"
  },
  {
    "caption": "(F-G) Hela OPTN/NDP52  knockdown cells were incubated with 1,2-Dipalmitoyl-sn-glycerol (DPG) followed by CCCP  treatment for 18 hrs. Mitophagy  efficiency was assessed by TOM20 staining  and quantified in (G) (n = 2 biological replicates). Note that DPG  significantly restored mitophagy  in OPTN/NDP52  knockdown cells. Scale bar = 10 µM.",
    "ncbi_link": "NDP52: 10241
OPTN: 10133"
  },
  {
    "caption": "(C). Cytosolic  and mitochondrial  fractions purified from control and OPTN/NDP52  knockdown cells treated with CCCP  were immunoblotted  with indicated antibodies. Note that mitochondrial EndoB1  levels were reduced in OPTN/NDP52  knockdown cells",
    "ncbi_link": "NDP52: 10241
OPTN: 10133"
  },
  {
    "caption": "(D-E) Hela  cells were transfected with an EndoB1  siRNA, followed by the expression plasmids for mCherry-Parkin  and YFP-DAGR, and CCCP  treatment (10 µM) for 9 hrs. Cells with mitochondrial YFP-DAGR were quantified in (E) (*P<0.05, Student's t-test, n=3 biological replicates). Scale bar = 25 µM and zoom is 5x. Note that knockdown of EndoB1  suppressed mitochondrial DAG  production.",
    "ncbi_link": "mCherry: 
YFP: 
Parkin: 5071
EndoB1: 51100"
  },
  {
    "caption": "(A, B) The  Mouse macrophage J774A.1 cell line was transfected with control siRNA or siRNA against IKKβ (A) or  IKKα  (B). 72 h post-transfection, the cells were co-stimulated for 60 min without (-) or with (+) 100 ng/ml LPS  and/or 5 μM nigericin. Cell lysates (10 μg) were denatured in SDS, subjected to SDS-PAGE  and  immunoblotted with the antibodies indicated. Similar results were obtained in three (A) or two (B) independent experiments.",
    "ncbi_link": "IKKα: 12675
IKKβ: 16150"
  },
  {
    "caption": "(C, D) As in (A, B) except that BMDM from  IKKβ-LysM-Cre (flox/flox) (IKKβ (fl/fl)) or WT control mice were co-stimulated without (-) or with (+) 100 ng/ml LPS  and/or 4 mM ATP (C) or with 100 ng/ml  LPS and/or 5 μM nigericin (D). Similar results were obtained in two independent experiments.",
    "ncbi_link": "LysM: 
Cre: 2777477
IKKβ: 16150"
  },
  {
    "caption": "(A, B) WT BMDM were incubated for 1 h without (-) or with (+), the  IKKβ inhibitors BI605906 (5 μM), TPCA-1 (5 μM) or  PS1145  (10 μM), the TAK1 inhibitor NG25  (2 μM) or the  NLRP3  inhibitor  MCC950. The cells were then co-stimulated for 30 min without (-) or with (+) 100 ng/ml LPS and/or 4 mM ATP  (A) and/or 5 μM nigericin (B). The cell culture medium was removed and the cells lysed. Protein in the culture medium was  precipitated (see Methods), dissolved in  SDS. and subjected to SDS-PAGE, along with cell lysates. After transfer to PVDF membranes, immunoblotting was performed with antibodies recognizing both full length (FL) and cleaved (CL)  gasdermin D (GSDMD), the p20  and p10 fragments of caspase-1  and IL-18. Similar results were obtained in two independent experiments. (C) As in A, except that iBMDM from IKKβ-CXCR3-Cre (flox/flox) (IKKβ (fl/fl) and control WT cells were used. Similar results were obtained in three independent experiments. ",
    "ncbi_link": "Cre: 2777477
CXCR3: 12766
IKKβ: 16150"
  },
  {
    "caption": "(C, As in A, B except that iBMDM from  IKKβ-CXCR3-Cre (flox/flox) mice  (IKKβ (fl/fl)) were used. The U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) was used as a loading control. Similar results were obtained in two independent experiments.",
    "ncbi_link": "Cre: 2777477
CXCR3: 12766
IKKβ: 16150"
  },
  {
    "caption": "(E, F) As in A, B except that BMDM from caspase-1 KO mice were used. Similar results were obtained in two independent experiments.",
    "ncbi_link": "caspase-1: 12362"
  },
  {
    "caption": "(I-L) As in A-H, except that IKKβ  inhibitors were omitted and iBMDM from IKKβ-CXCR3-Cre (flox/flox) (IKKβ (fl/fl)) or WT mice  were co-stimulated for 1 h with 100 ng/ml LPS and 10 μM nigericin or left unstimulated (control). Scale bar = 50 μm.",
    "ncbi_link": "Cre: 2777477
CXCR3: 12766
IKKβ: 16150"
  },
  {
    "caption": "(I-L) As in A-H, except that iBMDM from IKKβ-CXCR3-Cre (flox/flox) (IKKβ  (fl/fl) or WT  mice  were co-stimulated for 1 h with 100 ng/ml LPS and 10 μM nigericin or left unstimulated. Similar results were obtained in two independent experiments. Data information: In all panels, scale bar = 50 μm. ",
    "ncbi_link": "Cre: 2777477
CXCR3: 12766
IKKβ: 16150"
  },
  {
    "caption": "(D) Absolute  cell numbers of the indicated cell types were determined by flow-cytometric analysis of the  bone marrow from 3-week-old Pax5+/+ and Pax5Jak2/+ mice. Average cell numbers are shown with SEM and were statistically analyzed by multiple t-tests (unpaired two-tailed with Holm-Šídák's correction); ns, not significant (P > 0.05). One of 3 independent experiments is shown.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(F) Kaplan-Meier survival  analysis of  Pax5Jak2/+ (black) and control Pax5+/+ (grey) mice. n, number of mice analyzed. A P value of < 0.0001 was determined for the   survival curves by statistical analysis with the log-rank (Mantel-Cox) test.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(H)  Eosin-hematoxylin-stained  sections of the lung and liver of a  Pax5Jak2/+ tumor mouse.  Infiltrating and blasting tumor cells  are indicated by an arrow.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(I)  Flow-cytometric  analysis of   lymph node cells from a control Pax5+/+ mouse and a 10-week-old Pax5Jak2/+ tumor mouse. (J) Flow-cytometric analysis of B220lowCD19+ B cells  from the bone marrow of a 4-week-old Pax5Jak2/+ mouse.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(D-G) GSEA analysis of 327 repressed (D) or 330 activated (F) Pax5  target genes identified in  pro-B cells as compared with the ranked log2-fold gene expression changes in  Pax5Jak2/+ (PJ)  B-ALLs versus control (Ctrl)  Pax5+/- Cdkn2ab+/- B-ALLs (left). NES, normalized enrichment score. The expression of five genes that are upregulated in  Pax5Jak2/+ B-ALL cells (upper row) and Pax5-/- (KO) pro-B cells (lower row) is shown in (E). Likewise, the  expression of five genes that are upregulated in control B-ALL cells (upper row) and Pax5+/+ (WT) pro-B cells  (lower row) is shown in (G). TPM, transcripts per million. Mean TPM values with SEM are shown for the following RNA-seq experiments: 3 (WT  pro-B), 2 (KO pro-B), 2 (Ctrl B-ALL), and 4 (PJ B-ALL).",
    "ncbi_link": "Cdkn2a: 12578
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(H) Expression of the Ptprc  (CD45) gene from exon 3 to exon 8, as determined by  RNA-seq  of Pax5Jak2/+ and  Pax5+/- Cdkn2ab+/- B-ALL cells. The alternatively spliced exons 4 (A), 5 (B) and 6 (C) are indicated in orange in the respective exon-intron structure of the Ptprc  gene. Ptprc  transcripts of B220+ Pax5+/- Cdkn2ab+/- B-ALL cells contain all three exons, thus giving rise to expression of the CD45 isoform   RABC  (known as   B220). In contrast, reads at exon 4 are barely detectable and reads at exon 6 are strongly reduced in the mRNA of Pax5Jak2/+ B-ALL  cells, which likely gives rise to the  CD45 isoforms RBC and RB",
    "ncbi_link": "Cdkn2a: 12578
Jak2: 3717
Pax5: 18507
Ptprc: 19264
B220: 19264
CD45: 19265"
  },
  {
    "caption": "(D) Flow-cytometric  analysis of bone marrow cells  from 4-week-old Pax5ihCd2/+ and  Pax5Jak2/ihCd2 mice. The  expression of  human (h) CD2  from the Pax5ihCd2 allele is shown for CD19+B220+ (grey) and  CD19+B220low (black) B cells.",
    "ncbi_link": "Cd2: 914
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(G) Kaplan-Meier survival  analysis of Cd79a-Cre Ikzf1neo/+ Pax5LSL-Jak2/+ (black) and Cd79a-Cre Pax5LSL-Jak2/+ (grey)  mice. Statistical analysis of the  survival  curves was performed with the log-rank (Mantel-Cox) test; ****P < 0.0001. n, number of mice analyzed.",
    "ncbi_link": "Cd79a: 12518
Cre: 2777477
Ikzf1: 22778
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(H)  Flow-cytometric analysis of  B220 and CD19 expression  in  B-ALL  tumor cells from the  lymph node  of a Cd79a-Cre Ikzf1neo/+ Pax5LSL-Jak2/+ mouse (black; left). Pax5 expression  in these B-ALL  tumor cells (black line) and control  Pax5+/+ lymph node B cells (grey filled) was determined by intracellular  Pax5 staining (right).",
    "ncbi_link": "Cd79a: 12518
Cre: 2777477
Ikzf1: 22778
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(B,  Flow-cytometric  analysis of bone marrow and spleen from  Pax5Jak2-KD/+ (black; n = 11) and control  Pax5+/+ (grey; n = 7)  mice  at the age of 6-8 weeks. The frequencies of the indicated B cell  types are shown for each organ (B). The data are presented as mean percentages with SEM and were statistically analyzed by multiple t-tests (unpaired and two-tailed with Holm-Šídák's correction); ns (P > 0.5), *P < 0.05, **P < 0.01.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(B) Genome-wide  binding of Pax5-Jak2 in in vitro cultured pro-B cells from Pax5Jak2/+ Rosa26BirA/+ mice  at the age of 3 weeks (expressing  Pax5) and ex vivo Pax5Jak2/+ Rosa26BirA/+ B-ALL tumors (lacking Pax5), as determined by Bio-ChIP-seq analysis The DNA-binding  pattern of full-length  Pax5  was determined by  Bio-ChIP-seq  analysis of ex vivo sorted Pax5Bio/Bio pro-B cells, which carried a C‐terminal biotin acceptor sequence together with an  IRES‐BirA gene insertion in the 3' untranslated region of  Pax5  Two independent Bio-ChIP-seq experiments were performed for each cell type. Representative  binding patterns of Pax5 and Pax5-Jak2 in the three B cell  types are shown for a selected genomic region, with horizontal bars indicating Pax5  or Pax5-Jak2  peaks that were identified by MACS peak calling (left). The number of Pax5 (white) and  Pax5-Jak2  (grey or black) peaks, which were defined by stringent MACS peak calling with a P value of < 10-10 in the three B cell types, are shown to the right.",
    "ncbi_link": "BirA: 948469
Rosa26: 14910
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(F, G) Flow-cytometric  analysis of the bone marrow and spleen  from  Pax5Prd*-Jak2 /+ (black; n = 6) and control Pax5+/+ (grey; n = 5)  mice at the age of 6-7 weeks. The frequency of the indicated B cell  types in each organ is indicated in (F), and the  flow-cytometric analysis of  CD19  and B220 expression on  bone marrow B cells  is shown in (G). Statistical data are shown as mean percentages with SEM and were analyzed by multiple t-tests (unpaired and two-tailed with Holm-Šídák's correction): ns > 0.05; *P < 0.05; **P < 0.01. Each dot corresponds to one mouse.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(H) Kaplan-Meier survival  analysis of Pax5Prd*-Jak2 /+ (black) and  Pax5+/+ (grey) mice. A P value of < 0.0001 was determined for the   survival  curves by statistical analysis with the log-rank (Mantel-Cox) test. n, number of  mice analyzed.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(D) Immunoblot analysis of whole-cell extracts prepared from Pax5Jak2/+ and control  Pax5Etv6/+ Cdkn2ab+/- B-ALL   cells as well as from the human HEL, TMD8 and  K1106 cell lines. Phosphorylated (p) STAT5 was detected with an anti-STAT5 (pY694) antibody and the pY41-peptide with the purified anti H3Y41ph antibody One to five pY41-peptides were coupled to  ubiquitin, which was added in the range of 50 ng per well. The Gapdh and histone H3 proteins were analyzed as loading control. An unspecific protein is denoted by an asterisk. One representative of 5 immunoblot experiments is shown.",
    "ncbi_link": "Cdkn2a: 12578
Etv6: 14011
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(A,  Tumor progression  in Il7+/+ (grey), Il7+/- (dashed) and  Il7-/- (black) mice transplanted with Pax5Jak2-Luc/+ tumor cells, as determined by bioluminescence  measurements at the indicated days after cell transfer. Images of three transplanted  mice for each Il7 genotype are shown at the indicated days after cell transfer",
    "ncbi_link": "Il7: 16196"
  },
  {
    "caption": "(C)  Kaplan-Meier survival  analysis of Il7+/+,  Il7+/- and Il7-/- mice transplanted with Pax5Jak2-Luc/+ tumors cells. Statistical analysis of the  survival curves  was performed with the log-rank (Mantel-Cox) test; ns P > 0.05, *P < 0.05, **P < 0.01.",
    "ncbi_link": "Luc: 
Il7: 16196
Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(E) Quantification of the median fluorescence intensity (MFI) values of the p-STAT5 levels determined by intracellular staining  of splenic FO B cells from Pax5+/+ (grey), Pax5Jak2/+ (black) and  Pax5Jak2-KD/+ (white)  mice  at the age of 3-10 weeks Statistical data are presented as mean values with SEM and were analyzed by the two-tailed unpaired Student's t-test: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot corresponds to one mouse.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(F) Flow cytometric analysis of p-STAT5  levels in pro-B cells (B220+CD19+Kit+IgM-) and leukemic B220low B cells  of Pax5Jak2/+ mice (black) as well as in control pro-B cells of Pax5+/+ (WT) mice (grey) at the age of 4-5 weeks. A representative  flow cytometric analysis of the bone marrow  of a Pax5Jak2/+ mouse (left) and representative intracellular p-STAT5 stainings  (middle) are shown. The p-STAT5 levels in  pro-B and  leukemic B220low B cells (right) are quantified as MFI values relative to that of  Pax5+/+ pro-B cells. Statistical data are presented as mean values with SEM and were analyzed by the two-tailed unpaired Student's t-test: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each dot corresponds to one mouse.",
    "ncbi_link": "Jak2: 3717
Pax5: 18507"
  },
  {
    "caption": "(I) Upregulation of the genes Cxcr5, Syndig1l  and Sema4a in Pax5Jak2/+ (PJ) B-ALL cells. Mean TPM values with SEM are shown for the following RNA-seq  experiments: 2 (Ctrl B-ALL), 4 (PJ B-ALL)",
    "ncbi_link": "Cxcr5: 12145
Jak2: 3717
Pax5: 18507
Sema4a: 20351
Syndig1l: 627191"
  },
  {
    "caption": "K) Identification of  Cxcr5, Syndig1l  and Sema4a as activated  STAT5 target genes. ChIP-seq  analysis identified STAT5-binding  regions at all three loci (K). Horizontal bars below the ChIP-seq track indicate STAT5-binding  regions identified by MACS peak calling. RPM, reads per million.",
    "ncbi_link": "Cxcr5: 12145
Sema4a: 20351
Syndig1l: 627191"
  },
  {
    "caption": "Western blots and quantification of RBM3 and GFP normalised to GAPDH in GFP-RBM3 i-neurons at 37°C or 32°C (72h).",
    "ncbi_link": "GFP: 
RBM3: 5935"
  },
  {
    "caption": "(A-B) Median GFP intensity of BFP-positive GFP-RBM3 i-neurons measured by flow cytometry upon the sgRNA/Cas9-mediated KO of top 30 positive (A) or negative (B) regulator candidates. Statistical analysis is performed between the specific and non-targeting sgRNA groups for positive regulators (A) or between the specific sgRNA and reporter groups for negative regulators (B) within the 37°C or 32°C (72h) population.",
    "ncbi_link": "Cas9: "
  },
  {
    "caption": "(C) qRT-PCR of RBM3 mRNA level normalised to 18s rRNA in i-neurons at 37°C or 32°C (72h).",
    "ncbi_link": "18s rRNA: 
RBM3: 5935"
  },
  {
    "caption": "RT-PCR of RBM3 mRNA (Exon 2-4) in i-neurons at 37°C or 32°C (72h) in the presence or absence of SMG1 inhibitor. PSI values of RBM3 PE are calculated based on the intensity of PE-included (red arrows) and PE-skipped (green arrow) isoforms.",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "qRT-PCR using a combination of primers targeting Exon 3a, Exon 3 or Exon 4-5 quantifies the PSI values of RBM3 PE (Exon 3a, including both 3a-L and 3a-S) relative to Exon 3 or Exon 4-5 at 37°C or 32°C (72h) in the presence or absence of SMG1 inhibitor.",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "RT-PCR of RBM3 mRNA (Exon 2-4) in HeLa cells at 37°C and 32°C (48h) in the presence or absence of SMG1 inhibitor. PSI values of RBM3 PE are depicted in the graph on the right.",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "Schematics and RT-PCR of RBM3 minigene (Exon 1-4), flanked by unique sequences (thick black bars) to distinguish it from endogenous transcripts during PCR amplification, expressed in HeLa cells at 37°C or 32°C (48h), in the presence or absence of SMG1 inhibitor. PSI values of RBM3 PE are depicted in the graph on the right.",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "(A-B) qRT-PCR quantifying the PSI values of RBM3 PE relative to RBM3 mRNA in WT i-neurons at 37°C (A) or 32°C (72h) (B), when NMD is blocked by SMG1 inhibitor. Statistical analysis is performed between the specific and non-targeting sgRNA groups. ",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "PSI values of RBM3 Exon 3a-L in control and HNRNPH1-knocked down K562 and HepG2 cells. RNA-Seq data from ENCODE Project, 2 isogenic replicates are included.",
    "ncbi_link": "HNRNPH1: 3187
RBM3: 5935"
  },
  {
    "caption": "(D-E) RT-PCR of endogenous RBM3 (D) and expressed RBM3 minigene (E) in control (scramble siRNA) or HNRNPH1-knocked down HeLa cells at 37°C or 32°C (48h), in the presence or absence of SMG1 inhibitor. The ratio of PSI values between HNRNPH1 KD and control is shown for only the SMG1 i-treated conditions.",
    "ncbi_link": "HNRNPH1: 3187
RBM3: 5935"
  },
  {
    "caption": "(F-G) RT-PCR of endogenous RBM3 (F) and expressed RBM3 minigene (G) in SMG1 inhibitor-treated control (untransfected) or FLAG-HNRNPH1-overexpressing (OX) HEK293T cells at 37°C. PSI values of RBM3 PE are shown in the graphs on the right respectively. ",
    "ncbi_link": "FLAG: 
HNRNPH1: 3187
RBM3: 5935"
  },
  {
    "caption": "WT i-neurons are transduced with lentiviral constructs expressing BFP (Control) or HNRNPH1-T2A-BFP (HNRNPH1 overexpression, OX) at 37°C and 32°C, followed by RT-PCR of endogenous RBM3 with 24h SMG1 inhibitor treatment. PSI values of RBM3 PE are shown in the graph on the right.",
    "ncbi_link": "BFP: 
HNRNPH1: 3187
RBM3: 5935"
  },
  {
    "caption": "RT-PCR of WT and delGGGG RBM3 minigenes in HeLa cells at 37°C or 32°C (48h) treated with SMG1 inhibitor. PSI values of RBM3 PE are shown in the graphs on the right.",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "BrdU incorporation reflecting DNA synthesis and SA-b-gal activity as markers of CTX-induced senescence in Em-myc transgeniccontrol;Bcl2 versus Suv39h12;Bcl2lymphomas in vivo. Numbers represent mean percentages of positive cells6s.d. (n55 each).",
    "ncbi_link": "Bcl2: 12043
Suv39h1: 20937"
  },
  {
    "caption": "b, Representative whole-body FLT- and FDG-PET scans of an individual control;Bcl2 lymphoma-bearing mouse at tumour manifestation (untreated) and at day 6 after a single dose of CTX. Red circles, areas of specific tracer retention; green circles, matching areas with lost retentions. Specific tracer uptake was assessed by calculation of tumour-to-background ratios. Data represent mean ratios ± s.d. (n = 5 mice for FLT-PET scans and n = 6 mice for FDG-PET scans). Insets show representative Ki67 staining and colour-calibrated (red, highest intensities; blue, lowest intensities) bioluminescence images of glucose levels in tissue sections of the respective groups.",
    "ncbi_link": "Bcl2: 12043"
  },
  {
    "caption": "c, Intracellular glucose concentrations in untreated and ADR-treated control;Bcl2 (that is, senescent) versus Suv39h1-;Bcl2 (that is, non-senescent) lymphomas in vitro (as in d-g). Results represent means ± s.d. (n = 5 each).",
    "ncbi_link": "Bcl2: 12043
Suv39h1: 20937"
  },
  {
    "caption": "d, Extracellular levels of the specified metabolite-to-glucose ratios in the indicated lymphoma cells groups relative to untreated control;Bcl2 lymphoma cells after 18 h of cultivation. Data represent mean ratios ± s.d. (n = 4 each, measurements were carried out in duplicate). Note that glucose-6-phosphate is not detectable (n.d.) in the medium. Insets show (ADR-treated relative to untreated) intracellular levels of the respective metabolites after labelling with 13C6-glucose for one representative lymphoma from each group. Data represent mean ratios (see Supplementary Fig. 5 for an assessment of the heterogeneity of the TIS-associated hypermetabolism and a comparison of the metabolic parameters of individual lymphomas).",
    "ncbi_link": "Bcl2: 12043"
  },
  {
    "caption": "e, Immunoblot analyses of phosphorylated AMP-activated protein kinase (pAMPK), total AMPK, pyruvate kinase isoforms M1 and M2 in ADR-senescent control;Bcl2 versus ADR-treated Suv39h1-;Bcl2 lymphoma cells in vitro (n = 3 each; α-tubulin as a loading control. Gels were cropped to ease presentation; full-length blots are provided in Supplementary Fig. 16).",
    "ncbi_link": "Bcl2: 12043
Suv39h1: 20937"
  },
  {
    "caption": "f, Mean OCRs in ADR-senescent control;Bcl2 versus ADR-treated Suv39h1−;Bcl2 lymphoma cells in vitro. Results represent means ± s.d. (n = 5 each).",
    "ncbi_link": "Bcl2: 12043
Suv39h1: 20937"
  },
  {
    "caption": "a-e, Cell viability by trypan blue dye exclusion in ADR-senescent control;Bcl2 versus ADR-treated Suv39h1-;Bcl2 lymphoma cells at day 5 compared to the untreated condition in various biochemical, pharmacological or genetic interventional settings in vitro. All results in this figure represent means ± s.d. (n = 5 each). a, Inhibition of glucose metabolism by phloretin, cytochalasin B, and sodium oxamate.",
    "ncbi_link": "Bcl2: 12043
Suv39h1: 20937"
  },
  {
    "caption": "c, Lentiviral knockdown of hexokinase 2 (Hk2) by short hairpin RNA (shHk2). d, Inhibition of AMPK by compound C. e, Block of fatty acid oxidation by the carnitine palmitoyltransferase I inhibitor etomoxir. f, Inhibition of the electron transport chain by antimycin A. *P  0.01, except b (n = 8 each) and e, in which *P  0.05.",
    "ncbi_link": "hexokinase 2: 15277"
  },
  {
    "caption": "Proteostasis analysis in TIS control versus senescence-incapable lymphoma cells in vitro, as in Fig. 2, or versus SASP-attenuated TISlymphoma cells. a, Global protein synthesis rate, measured by incorporation of green-fluorescent methionine. Mean fluorescent intensities reflect newly synthesized protein within 2 h (DAPI used as a counterstain). Data represent means ± s.d. (n = 5 each). b, Rate of global protein synthesis (measured as in a) in ADR-senescent relative to untreated (ut) control;Bcl2 lymphoma cells; either empty vector-infected cells or cells stably expressing the NF-kB super-repressor IkBaDN(SR, ref. 18). Results represent means ± s.d. (n = 5 each). c, Relative intracellular glucose concentrations in cells as in b.",
    "ncbi_link": "Bcl2: 12043
IkBaDN: 18035"
  },
  {
    "caption": "f, Expression of the transcription factors Xbp1 (by RT-PCR (PCR with reverse transcription; top); note that the lower band reflects the UPR-related splice form), ATF4, CHOP, phospho-Jun N-terminal kinase (JNK-P-Thr183/Thr185) and total JNK(by immunoblot analysis, with a-tubulin as a loading control; bottom) in lymphoma cells as indicated (n = 3 each, gels were cropped to ease presentation; full-length blots are provided in Supplementary Fig. 16).",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "a, Cellular viability of super-repressor- or empty-vector-infected control;Bcl2 lymphomas treated with ADR or untreated for 5 days, then exposed for 2 days to the inhibitors 2DG or bafilomycin A1, compared to no inhibitor (ut) in vitro. Results represent means ± s.d. (n = 5 each).",
    "ncbi_link": "Bcl2: 12043"
  },
  {
    "caption": "b, Immunoblot analyses of ATF4, global protein ubiquitination, p62/SQSTM1, and MAP1-LC3-I to MAP1-LC3-II conversion in control;Bcl2 lymphomas with no ADR treatment, in TIS cells, and in TIS cells after exposure to 2DG or bafilomycin A1in vitro; representative blot with α-tubulin as a loading control (gels were cropped to ease presentation; full-length blots are provided in Supplementary Fig. 16). c, Cleavage (activation) of caspase 12 and detection of cleaved caspase 3 by immunoblot analysis of control;Bcl2 lymphomas as in b; representative blot with α-tubulin as a loading control (gels were cropped to ease presentation; full-length blots are provided in Supplementary Fig. 16).",
    "ncbi_link": "Bcl2: 12043"
  },
  {
    "caption": "d, Cellular viability of ADR-treated control;Bcl2 lymphoma cells infected with short-hairpin RNAs against either caspase 12 (shCasp12) or caspase 3 (shCasp3) compared to empty vector-infected lymphoma cells treated as in a. Results represent means ± s.d. (n = 4 each).",
    "ncbi_link": "Bcl2: 12043
caspase 12: 12364
caspase 3: 12367"
  },
  {
    "caption": "h, Colour-coded whole-body fluorescence imaging to visualize green fluorescent protein (GFP)-tagged tumour burden in time-courses of three representative mice harbouring CTX-senescent control;Bcl2 lymphomas at day 5 (see Figure 1a), and two days later, after the administration of 2DG (n = 3 mice), bafilomycin A1 (n = 4 mice) or mock treatment (n = 4 mice) starting from day 5 post CTX (red, highest intensities; blue, lowest intensities). TdT-mediated dUTP nick end labelling (assay) (TUNEL) staining of lymph node sections in situ to visualize apoptosis at day 7. Numbers represent means ± s.d. (n = 3).",
    "ncbi_link": "Bcl2: 12043"
  },
  {
    "caption": "i, Overall survival of 5 day-CTX-treated control;Bcl2 or Suv-39h1-;Bcl2 lymphoma-bearing mice randomly assigned to sequential exposure to bafilomycin A1 or mock as in h (control;Bcl2: n = 12 and Suv39h1-;Bcl2: n = 10), presented as matched pair analyses (P<0.001 for the control; Bcl2 comparison; P = 0.221 for the Suv39h1-;Bcl2 comparison). *P<0.05.",
    "ncbi_link": "Bcl2: 12043
Suv-39h1: 20937
Suv39h1: 20937"
  },
  {
    "caption": "g, Expression of CPAP-GFP or CPAP-CC5-GFP in Seckel NPCs slightly increases nestin-positive cells (i), decreases neuronal differentiation (for CC5 *p<0.05) (ii), decreases ciliary length (for CPAP ***p<0.001 and for CC5 **p<0.01) (iii), elevates mitotic index (for CC5 *p<0.05) (iv) and decreases the number of ciliated cells (for CPAP *p<0.05 and for CC5 **p<0.01) (v) compared to control (mock electroporation). Error bars show s. e. m. One-way ANOVA followed by Tukey's multiple comparisons test. n = 3 independent experiments with >350 (nestinstaining, differentiation and mitotic index), and >70 cells (cilium length) cells.",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "a-b, siRNA-mediated down regulation of CDC components in WT NPCs causes longer cilia (Ofd1 ***p<0.001, Nde1 **p<0.01), retarded cilia disassembly as shown by increased numbers of ciliated cells (Ofd1 **p<0.01, Nde1 *p<0.05) and differentiation of NPCs into TUJ1 positive cells (Ofd1 **p<0.001, Nde1 *p<0.01). In controls, a non-targeting siRNA (scrambled) is used. Western blots at right validate siRNAs-mediated Nde1 and OFD1 depletion. Error bars are s. e. m. Ordinary Two-way ANOVA followed by Sidak's multiple comparisons test. n = 3 independent experiments. 275 cells for scrambled, 423 cells for Ofd1 siRNA and 255 cells for Nde1 siRNA.",
    "ncbi_link": "Nde1: 54820
Ofd1: 8481
OFD1: 8481"
  },
  {
    "caption": "a-b, siRNA-mediated down regulation of CDC components in WT NPCs causes longer cilia (Ofd1 ***p<0.001, Nde1 **p<0.01), retarded cilia disassembly as shown by increased numbers of ciliated cells (Ofd1 **p<0.01, Nde1 *p<0.05) and differentiation of NPCs into TUJ1 positive cells (Ofd1 **p<0.001, Nde1 *p<0.01). In controls, a non-targeting siRNA (scrambled) is used. Western blots at right validate siRNAs-mediated Nde1 and OFD1 depletion. Error bars are s. e. m. Ordinary Two-way ANOVA followed by Sidak's multiple comparisons test. n = 3 independent experiments. 275 cells for scrambled, 423 cells for Ofd1 siRNA and 255 cells for Nde1 siRNA.",
    "ncbi_link": "Nde1: 54820
Ofd1: 8481"
  },
  {
    "caption": "d, Cell cycle progression of siRNA or VX680 treated WT NPCs compared to control assessed by EdU incorporation for 24 hours. Inhibition of Ofd1 (*p<0.05), Nde1 (**p<0.01) and Aurora A (***p<0.001) caused significantly reduced incorporation of EdU.",
    "ncbi_link": "Nde1: 54820
Ofd1: 8481"
  },
  {
    "caption": "e-g, Western blots show that CPAP targeting siRNA treatment depletes endogenous CPAP. Both low -and high -exposures are given (e). Increased cilia length and NPC differentiation upon expression of RNAi-resistant CPAP E1235V compared to WT CPAP (f-g). Error bars are s. e. m. *** p<0.001 (cilia length), * p<0.05 (differentiation), t-test. For cilia length: n = 4 independent experiments. 25 cells for CPAP, 47 cells for CPAP E1235V. For differentiation: n = 4 independent experiments. 145 for CPAP and 81 for CPAP E1235V. Scale bar 1 μm.",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "d, Seckel organoids electroporated with constructs expressing GFP alone (i), GFP with CC5-GFP and (ii) GFP with CPAP-GFP (iii). Middle panel shows staining with anti-GFP antibodies (red) to show the transfected area. Note the presence of increased Pax6-positive (magenta) NPCs in CC5 and CPAP electroporated tissues compared to GFP control. Likewise, there is a larger neural epithelium with multiple RGs (arrowheads). Bar diagrams at right shows rescue effects of CPAP and CC5 electroporation compared with GFP alone (iv) lower TUJ1/Pax6 ratio (**p<0.01 and ***p<0.001 respectively) (v) smaller lumen diameter (**p<0.01) and (vi) shorter cilia length (**p<0.01 and ***p<0.001 respectively). Error bars are s. e. m. One-way ANOVA followed by Dunnett's multiple comparisons test. n = 3 organoids with 225 cells for GFP, 537 cells for CPAP and 569 for CC5. At least 10 ventricles from 3 independent organoids were used to measure the CPAP diameter. t test. Error bars are s.e.m. Scale bar 20 μm.e, Rescue effect of CC5 and CPAPelectroporation on cleavage planes of phospho-vimentin-positive RGs in Seckel organoids. Compared to GFP control, electroporation of CC5 or GFP increases the proportion of horizontally orientated SeckelRGs (for CC5 ***p<0.001) and decreases the portion of obliquely (for CC5 *p<0.05) or vertically oriented SeckelGFP (for CPAP and CC5 **p<0.01). Error bars are s.e.m. Two-way ANOVA followed by Tukey's multiple comparisons test. n = 4 organoids. 100 cells for GFP control, 112 cells for CPAP and 99 cells for CC5.",
    "ncbi_link": "CPAP: 55835
CPAP: Q9HC77///55835"
  },
  {
    "caption": "(B) Quantification of the Snap29 signal as in panel A, considering > 30 KTs per sample. Relative mRNA expression of the downregulated genes versus control, measured by Q-PCR, is shown above the graph. Note that efficient depletion of Zw10 does not affect Snap29 localization to KTs.",
    "ncbi_link": "Zw10: 47874"
  },
  {
    "caption": "(C) Comparable maximum projections of confocal sections of dorsal wing pouches in which Snap29 has been downregulated and the indicated Snap29 form over-expressed. Cartoons of the expressed Snap29 mutant forms are shown above the panels. Anti-pH3 labels mitotic cells and CenpC marks KTs. (D) Quantification of Snap29 as in panel C, considering > 28 KTs per sample. Note that expression of a form of Snap29 lacking the SNARE1 domain does not rescue Snap29 localization to KTs in Snap29 RNAi cells.",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(A) Selected frames of time-lapse imaging of control S2 cells or cells treated for 96 hrs with dsRNA against the central portion of Snap29. Note that depleted cell does not display a recognizable metaphase plate, or fail to segregate all chromosomes correctly, or form tripolar spindles or micronuclei (arrowheads; arrowheads in control point to cells dividing normally).",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(B) Western blotting of extract from control cells and cells depleted of Snap29 (dsSnap29) relative to the experiment in a.",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(C) Quantification of the mitotic phenotype of control and dsSnap29 depleted cells, based on time-lapse imaging of an average of > 28 individual cells per sample. P value is determined by two-tailed t-test considering all defects together.",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(A) Single confocal sections of HeLa cells at metaphase treated for 8 min at 4°C and immunostained to reveal the presence of unattached kinetochores. CENPT labels all KTs, while MAD1 identifies unattached ones. Enlargements of boxed areas displaying both chromosomes aligned and not aligned at the metaphase plate. (B) Quantification of the number of KTs based on attachment, position and MAD1 positivity. Each point per category represents one experiment in which 10 random KTs/cell of 20 cells/sample were counted. P values are obtained by 2-way ANOVA with Dunnett's multiple comparison test. Note that in control cells most of the KT are attached, MAD1-negative and aligned to the metaphase plate, while in SNAP29KD cells half of the KTs that are unattached, MAD1-positive and not aligned to the metaphase plate.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(A-C, E) Max projection of single control and SNAP29 KD HeLa cells treated with 2 mM thymidine for 24 hrs, released in normal medium for 8 hrs and arrested in prometaphase with Nocodazole for 2 hrs.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(A-C, E) Max projection of single control and SNAP29 KD HeLa cells treated with 2 mM thymidine for 24 hrs, released in normal medium for 8 hrs and arrested in prometaphase with Nocodazole for 2 hrs.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(A-C, E) Max projection of single control and SNAP29 KD HeLa cells treated with 2 mM thymidine for 24 hrs, released in normal medium for 8 hrs and arrested in prometaphase with Nocodazole for 2 hrs.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(A-C, E) Max projection of single control and SNAP29 KD HeLa cells treated with 2 mM thymidine for 24 hrs, released in normal medium for 8 hrs and arrested in prometaphase with Nocodazole for 2 hrs.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(F) Quantification of 3 independent experiments evaluating the localization of the KT factors shown in A-C, e relative to CREST. 100 KTs from 10 control cells and 200 KTs from 10 SNAP29 KD cells per sample were identified by CREST staining. P values are obtained by 2-way ANOVA with Sidak's multiple comparison analysis relative to localization of HEC1, which is not lost on SNAP29KD cells.",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(A-C) KNL1 localization analysis in control, SNAP29 KD and SNAP29 KD expressing full length human SNAP29, CFP tagged, full length Drosophila Snap29 (CFP-Snap29), or the mutant forms schematized above the panels. Max projections of single cells in prophase are shown. (D) Quantification of 3 independent experiments evaluating the localization of KNL1 relative to CREST. 200 KTs from 10 control cells and 200 KTs from 10 SNAP29 KD cells per sample were identified by CREST staining. P values are obtained by 2-way ANOVA with Dunnett's multiple comparison analysis relative to localization of KNL1 in SNAP29KD cells.",
    "ncbi_link": "Snap29: 37774
SNAP29: 9342"
  },
  {
    "caption": "(E-F) Single confocal sections of HeLa cells in interphase overexpressing the indicated constructs. In cells expressing SNAP29 Q1 Q2, SNAP29 and KNL1 accumulate in large compartments that are often positive for p62 (arrows).",
    "ncbi_link": "SNAP29: 9342"
  },
  {
    "caption": "(C) High magnification of a single confocal cross-section of wild-type and Snap29 mutant eye disc tissues. Two facing folds of the tissue are separated by the apical lumen. aPKC and Dlg mark the apical and lateral plasma membrane domains, respectively. In Snap29 mutant tissue the apical-basal polarity is disrupted.",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(D) Single confocal cross-sections of wild-type and Snap29 eye-antennal discs, expressing Puckered-LacZ (Puc-lacZ), a reporter of JNK signaling activation.",
    "ncbi_link": "Snap29: 37774"
  },
  {
    "caption": "(E-H) Single confocal cross-sections of wild-type and Snap29 eye-antennal discs (E-F), and of otherwise wild-type and Snap29 eye-antennal discs expressing the bacterial apoptosis inhibitor p35 (G-H). Anti-activated-Caspase 3 (Casp3) marks apoptotic cells.",
    "ncbi_link": "p35: 
Snap29: 37774"
  },
  {
    "caption": "Representative images of combined IF for H3K27me3 or H2AK119ub (green) with RNA FISH for Xist (red) in Xist-TetOP lines (for clone 1 of each mutant type) upon D2 in DOX conditions; Blue - DAPI staining; Scale bar: 10 µm.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Graph represents the mean % + S.E.M. of Xist-coated X chromosomes enriched for H3K27me3 or H2AK119ub in the different Xist-TetOP mutants (for clone 1 of each mutant type) from 2-to-4 independent experiments; A minimum of 50 Xist-coated X chromosomes were counted per experiment; Only p-values corresponding to significant differences from unpaired Student's t-test comparing mutants to Xist FL are indicated as * (p-value < 0.05).",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Top 20 protein hits from the ChIRP-MS of Xist FL; The ranking was based on fold-enrichment of Xist FL DOX versus Xist FL noDOX; Weakly annotated protein isoforms with an Annotation score in UniprotKB < 3 (out of 5) were excluded; Fold-enrichment for Xist ΔB+C is also displayed for comparison; Light green boxes correspond to proteins as Xist interactors [13]; protein in red (RNF2/RING1B) represents a protein not found in the Xist ΔB+C interactome; Protein in light brown (TRIM71) is less enriched in Xist ΔB+C than in Xist FL.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Scatter plot displaying the differences in peptide counts between Xist FL and Xist ΔB+C for the 74 out of 81 Xist-interactors with a minimum of fold-change of 2.5 in Xist FL or Xist ΔB+C; Shown is the log2 fold change of peptide counts of each mutant in DOX conditions compared with the Xist FL in noDOX conditions; proteins retrieved by both Xist FL and Xist ΔB+C ChIRPs with a proposed role in XCI such as SPEN, RBM15, WTAP, YTHDC1 and hnRNPU are indicated; light brown dots mark proteins more represented in Xist FL than in Xist ΔB+C ChIRPs, while red dots display proteins which are only retrieved by Xist FL ChIRP.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Plots showing H3K27me3 and H2AK119ub accumulation over the X chromosome in Xist FL and Xist ΔB+C with upon DOX induction at day 2 (D2) of differentiation; Each dot represents a single 10Kb window and its enrichment relative to noDOX condition; Black line is a loess regression on all windows; Xist locus is represented by a blue long line, active genes by green lines.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Violin plots quantifying H3K27me3 and H2AK119ub enrichment over intergenic regions, active promoters and active gene bodies in the X chromosome in Xist FL and Xist ΔB+C cell lines at D2 upon DOX induction; Shown is the log2 fold change of DOX vs noDOX conditions; violin plots represent the distribution of the values, the horizontal band is the median, the lower and upper hinges correspond to the 25th and 75th percentiles; n = indicates the number of regions/genes analyzed; p-values were calculated using paired Wilcoxon test, comparing Xist FL and Xist ΔB+C cell lines.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Average plots showing the mean enrichment of H3K27me3 (top) and H2AK119ub (bottom) over all X-linked initially active transcriptional start sites (TSS); Shown is the mean of normalized log2 enrichment of DOX vs noDOX in both Xist FL and Xist ΔB+C cell lines.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Genome browser plots showing H3K27me3 (top) and H2AK119ub (bottom) enrichments in a region encompassing the inactive Atp1b4 and the initially active Lamp2 genes within the XqA3.3 region and the initially active Rlim/Rnf12 gene at the XqD region; Region around the promoter of Rlim/Rnf12 is highlighted in yellow.",
    "ncbi_link": "Atp1b4: 67821
Lamp2: 16784
Rlim: 19820
Rnf12: 19820"
  },
  {
    "caption": "Graph represents the mean % + S.E.M. of Xist-coated chromosomes presenting an active Pgk1 or Lamp2 gene as determined by RNA FISH (as represented in B) at D2 in the presence of DOX (Xist FL was also used in noDOX conditions) in the different Xist-TetOP mutants; each bar represents the mean from to 2-to-4 independent experiments; A minimum of 59 Xist-coated chromosomes were counted per experiment; For Xist FL noDOX a minimum of 100 cells (which do not have Xist-coated chromosome) were counted; Only p-values corresponding to significant differences comparing mutants (or Xist FL noDOX) to Xist FL DOX are indicated as * (p-value < 0.05) or *** (p-value < 0.01), unpaired Student's t-test; dashed line marks the mean percentage of silencing for the Lamp2 gene in Xist FL DOX.",
    "ncbi_link": "Lamp2: 16784
Pgk1: 18655
Xist: 213742"
  },
  {
    "caption": "Representative RNA FISH images for Xist (red) and nascent-transcript of Pgk1 (green) in Xist-TetOP lines at day 4 of differentiation in the presence of DOX (Xist FL is also shown in noDOX conditions); DNA stained in blue by DAPI; Numbers represent % of Xist-coated X-chromosomes ± S.E.M. with active Pgk1 gene (except for Xist FL noDOX, where numbers represent % of cells with Pgk1 active gene); The values represent 2-to-4 independent experiments, where a minimum of 50 Xist-coated chromosomes were counted per experiment; Significant differences compared with Xist FL (DOX) are indicated as * (p-value < 0.05) or *** (p-value < 0.01), unpaired Student's t-test.",
    "ncbi_link": "Pgk1: 18655
Xist: 213742"
  },
  {
    "caption": "Clustering analysis of the normalized RNA-seq counts on the X chromosome (chrX) for all the duplicates of Xist FL, Xist ΔA and Xist ΔB+C in DOX and noDOX conditions.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Plots displays the log2(fold-change) in the expression of X-linked genes along the chrX comparing DOX versus noDOX samples for Xist FL, Xist ΔA and Xist ΔB+C at day 2 of differentiation; red dots correspond to genes which are differently expressed in DOX vs noDOX (p < 0.05, Limma t-test), while black dots represent genes which are not differentially expressed between the two conditions (p ≥ 0.05).",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Violin plots displaying the average log2(fold-change) in gene expression between DOX and noDOX conditions on the chrX in Xist FL, Xist ΔA and Xist ΔB+C at day 2 of differentiation; violin plots represent the distribution of the values, the horizontal band is the median, the lower and upper hinges correspond to the 25th and 75th percentiles; p-values were calculated using paired Wilcoxon test; n = indicates the number of genes analyzed.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Box plots displaying the log2(DOX/noDOX) fold-change in expression of X-linked genes in Xist FL and Xist ΔB+C categorized according to the enrichment of H3K27me3 and H2AK119ub marks at promoters in Xist ΔB+C upon DOX induction (with no or little accumulation vs accumulation); the horizontal band of the boxplot is the median of the values, the lower and upper hinges correspond to the 25th and 75th percentiles, the upper whisker extends from the hinge to the largest value not further than 1.5 interquartile range from the hinge, the lower whisker extends from the hinge to the smallest value at most 1.5 interquartile range of the hinge; p-values between samples were calculated using paired Wilcoxon test; n = indicates the number of genes analyzed.",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Genome browser plots showing RNA-seq reads, H3K27me3 and H2AK119ub nChIP reads around the Abcb7 gene for Xist FL (left) and Xist ΔB+C (right) at day 2 of differentiation in both DOX and noDOX conditions.",
    "ncbi_link": "Abcb7: 11306
Xist: 213742"
  },
  {
    "caption": "B, C, Representative images of pPLT3::erCFP (cyan) expressing and PI-stained (red) Arabidopsis roots in Col or wox5 background, respectively. D, Mean fluorescence intensities of the pPLT3::erCFP roots summarized in box and scatter plots. The mean fluorescence intensity of the CFP signal in Col roots was to set to 100 %. D, Box = 25-75 % of percentile, whisker = 1.5 interquartile range, − = median, □ = mean value, = minimum/maximum. The data was statistically analyzed by one-way ANOVA and Holm-Sidak post-hoc multiple comparisons test. Asterisks indicate statistically significant differences (α = 0.01). Number of analysed roots (n) (biological replicates) is indicated for each genotype and results from two technical replicates. B, C, Scale bars represent 10 µm. PI = propidium iodide CFP = cyan fluorescent protein.",
    "ncbi_link": "wox5: 820297"
  },
  {
    "caption": "E, F, Representative images of pPLT3::PLT3-YFP (yellow) expressing and FM4-64-stained (red) Arabidopsis roots in Col or wox5 mutant background, respectively. g, Mean fluorescence intensities of the pPLT3::PLT3-YFP expressing roots summarized in box and scatter plots. The mean fluorescence intensity of the YFP signal in Col roots was to set to 100%. G, Box = 25-75 % of percentile, whisker = 1.5 interquartile range, − = median, □ = mean value, = minimum/maximum. The data was statistically analyzed by one-way ANOVA and Holm-Sidak post-hoc multiple comparisons test. Asterisks indicate statistically significant differences (α = 0.01). Number of analysed roots (n) (biological replicates) is indicated for each genotype and results from two technical replicates. , E, F, Scale bars represent 10 µm. YFP = yellow fluorescent protein",
    "ncbi_link": "wox5: 820297"
  },
  {
    "caption": "A-F, Representative FM4-64-stained Arabidopsis roots (grey) expressing pWOX5::mVenus-NLS (green) in Col, plt2, plt3 and plt2, plt3 double mutant background in longitudinal (A-D), or transversal (E-F) optical sections. E', F', Analysis of representative images in (E) and (F) in Imaris to detect and count individual expressing nuclei. E'', F'', Overlay of 10 roots (biological replicates) showing the area of detected fluorescence (high levels in red, low levels in blue) in Col and plt2, plt3 double mutant roots. G, Number of nuclei (biological replicates) expressing pWOX5::mVenus-NLS in Col and plt2, plt3 double mutant roots summarized in box and scatter plots. H, Area of WOX5 expression in µm2 in Col and plt2, plt3 double mutant roots summarized in box and scatter plots. G, H Box = 25-75 % of percentile, whisker = 1.5 interquartile range, − = median, □ = mean value, = minimum/maximum. (G, H) Kruskal-Wallis ANOVA analysis with subsequent Dunns test (G) or one-way ANOVA and post-hoc Holm-Sidak multiple comparisons test was used to test for statistical significance (H). Asterisks indicate statistically significant differences (α = 0.01). Number of analysed roots (n) (biological replicates) is indicated for each genotype and results from three technical replicates per genotype. Scale bars represent 10 µm; NLS = nuclear localisation signal.",
    "ncbi_link": "plt3: 830915
plt2: 841542"
  },
  {
    "caption": "I, Fluorescence lifetimes in ns are summarized in combined jitter and box plots. The dashed line represents the fluorescence lifetime mean value of the WOX5-mV  co-expressed with free mCh  as negative control. The one-way ANOVA and Holm-Sidak post-hoc multiple comparisons test was used to test for statistical significance. Samples with identical letters do not show significant differences (α = 0.01). Number of nuclei  analyzed (n) (biological replicates) is indicated and results from 2 to 9 technical replicates. Box = 25-75 % of percentile, whisker = 1.5 interquartile range, − = median, ▪ = mean value.",
    "ncbi_link": "mCh: "
  },
  {
    "caption": "LDH release assay from primary monocyte-derived macrophages (MDM) left untreated or treated with IFNγ, transfected with siRNA against GBP1 or non-targeting control (CTRL) and infected with indicated strain of Tg for 24 hours. Mean ± SEM of n = 4 donors shown.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "LDH release assay from indicated wildtype, GBP1 knockout (∆GBP1) or GBP1 reconstituted (∆GBP1+Tet-GBP1) cells infected with type I or type II Tg for 24 hours. Cells were untreated or treated with IFNγ or additionally treated with doxycycline (Dox) as indicated.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "LDH release assay from wildtype THP-1 or ∆GBP1 cells stably reconstituted with Dox-inducible expression plasmids of the indicated mutants of GBP1. Cells were pre-treated with IFNγ and Dox and infected with either type I or type II Tg for 24 h.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "Propidium iodide (PI) uptake in indicated wildtype THP-1 or ∆CASP-1, ∆CASP-4, ∆ASC cells, or THP-1 stably expressing GSDMD-targeting miRNA (GSDMDmiR) infected with the indicated strains of Toxoplasma gondii (Tg) for 24 h. Cells were untreated or treated with IFNγ as indicated. Mean area under the curve (AUC) ± SEM from n = 3 experiments are shown. ns, not significant, from two-way ANOVA following adjustment for multiple comparisons.",
    "ncbi_link": "CASP-1: 834
CASP-4: 837
GSDMD: 79792
ASC: 29108"
  },
  {
    "caption": "Real-time apoptosis assay (Annexin V (AnnV)-Glo luminescence) from IFNγ-primed primary human MDMs transfected with non-targeting control (siCTRL; left) or GBP1 siRNA (siGBP1; right) and left uninfected or infected with type I or type II Tg. Depicted is the mean ± SEM of n = 4 donors. AU, arbitrary units.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "AnnV-Glo assay from IFNγ-primed primary human MDMs transfected with siRNA against CASP8, CASP10 and non-targeting control (CTRL) and infected with type I or type II Tg. Area under the curve (AUC) from real-time assays similar to those in (B) are plotted from n = 4 independent experiments. Matched shapes and color of symbols indicate donors.",
    "ncbi_link": "CASP10: 843
CASP8: 841"
  },
  {
    "caption": "AnnV-Glo assay from IFNγ-primed primary human MDMs transfected with siRNA against AIM2 or non-targeting control (CTRL) and infected with type I or type II Tg. Area under the curve (AUC) from real-time assays are plotted from n = 4 independent experiments. Matched shapes and color of symbols indicate donors.",
    "ncbi_link": "AIM2: 9447"
  },
  {
    "caption": "Representative images (top) from IFNγ-primed THP-1 WT infected with type I Tg for 8 hours and stained for ASC and active caspase-8. Blue, Nuclei; Red, ASC; Green, active caspase-8 (IETD-FITC) and Grey, Tg. Scale bar, 5 μm or 2 μm in the magnified images. Quantification of ASC specks (bottom) in Tg-infected THP-1 WT or ∆CASP1 treated with IFNγ or left untreated at 8 hours post infection, plotted as mean ± SEM from n = 3 independent experiment.",
    "ncbi_link": "CASP1: 834"
  },
  {
    "caption": "Representative images (A) and quantification (B) from IFNγ-primed THP-1 ∆GBP1 stably reconstituted with Tet-mCH-GBP1, mCH-GBP1K51A, mCH-GBP1C589A or mCH-GBP1∆589-592 variants or monocyte derived macrophages (MDM) stained for GBP1. Cells were infected with type I or type II Toxoplasma gondii (Tg) for 2 h. Blue, Nuclei; Grey, Tg; Red, mCH-GBP1 or Magenta, GBP1. Scale bar, 5 μm. Graph in (B) shows mean percentage of Tg vacuoles targeted by GBP1 from n = 4 experiments.",
    "ncbi_link": "mCH: 
GBP1: 2633"
  },
  {
    "caption": "LDH release assay from indicated THP-1 cells untreated or treated with IFNγ and infected with Salmonella Typhimurium (STm) WT or a SPI-1 mutant ΔinvA for 4 h at indicated multiplicities of infection (MOI). Mean ± SEM of n = 3 experiments are shown.",
    "ncbi_link": "SPI-1: 6688"
  },
  {
    "caption": "Propidium iodide (PI) uptake assay from IFNγ-primed primary MDMs transfected with non-targeting control siRNA (CTRL) or siRNA against GBP1 (left) or indicated lines of THP-1 (right) infected with STm-GFP for 4 h. Area under the curve (AUC) from real-time assay plotted as mean ± SEM from n = 3 independent experiments.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "PI uptake assay from IFNγ-primed or untreated THP-1 ΔCASP-1 cells transfected with indicated siRNA and infected with STm-GFP for 4 h. Area under the curve (AUC) from real-time assay plotted as mean ± SEM from n = 3 independent experiments. Schematic on right shows overview of the pathway leading to caspase-1 and caspase-4 activation.",
    "ncbi_link": "CASP-1: 834"
  },
  {
    "caption": "Representative images from IFNγ-primed THP-1 ∆GBP1 cells stably reconstituted with Tet-mCH-GBP1, mCH-GBP1K51A, mCH-GBP1C589A or mCH-GBP1∆589-592 variants or primary MDMs stained for GBP1. Cells were infected with STm-GFP for 2 h. Blue, Nuclei; Grey, STm; Red, mCH-GBP1 or Magenta GBP1. Scale bar, 5 μm.",
    "ncbi_link": "mCH: 
GBP1: 2633"
  },
  {
    "caption": "quantification (G) from IFNγ-primed THP-1 ∆GBP1 cells stably reconstituted with Tet-mCH-GBP1, mCH-GBP1K51A, mCH-GBP1C589A or mCH-GBP1∆589-592 variants or primary MDMs stained for GBP1. Cells were infected with STm-GFP for 2 h. Blue, Nuclei; Grey, STm; Red, mCH-GBP1 or Magenta GBP1. Scale bar, 5 μm. Graph in (G) shows percentage of STm vacuoles targeted by GBP1.",
    "ncbi_link": "mCH: 
GBP1: 2633"
  },
  {
    "caption": "Representative images from THP-1 ∆GBP1+Tet-mCH-GBP1 cells stably expressing YFP-CASP4C258S. Cells were infected with STm for 2 h. Blue, Nuclei & STm (Hoechst dye); Red, mCH-GBP1; Green, YFP-CASP4C258S. Scale bar, 5 μm.",
    "ncbi_link": "mCH: 
YFP: 
CASP4: 837
GBP1: 2633"
  },
  {
    "caption": "Quantification of THP-1 ∆GBP1+Tet-mCH-GBP1 cells stably expressing YFP-CASP4C258S and infected with STm for 2 h. Graph shows percentage of STm vacuoles targeted by GBP1, CASP4 or both from n = 3 experiments. n.d. not detected.",
    "ncbi_link": "mCH: 
YFP: 
CASP4: 837
GBP1: 2633"
  },
  {
    "caption": "Cell death measured using Annexin V (AnnV)-Glo assay of THP-1 ∆CASP1 cells transfected with non-targeting control (CTRL) or GBP1 siRNA and treated as indicated. Cells were primed with IFNγ, transfected with soluble Tg antigen (STAg) or both, or left untreated (UT). Area under the curve (AUC) from real-time assay plotted as mean ± SEM from n = 3 independent experiments.",
    "ncbi_link": "CASP1: 834
GBP1: 2633"
  },
  {
    "caption": "AnnV-Glo assay from naïve or IFNγ-primed THP-1 ∆CASP-1 cells transfected with soluble Tg antigen (STAg) that was untreated (UT) or treated as indicated. Area under the curve (AUC) from real-time assay plotted as mean ± SEM from n = 3 independent experiments.",
    "ncbi_link": "CASP-1: 834"
  },
  {
    "caption": "Immunoblots from IFNγ-primed THP-1∆CASP-1 or THP-1 ∆ASC cells transfected with non-targeting control (CTRL), GBP1, AIM2, CASP-1 or CASP-8 siRNA and then untreated (-) or transfected with STAg for 12 h. Images are representative of n = 2 independent experiments.",
    "ncbi_link": "AIM2: 9447
CASP-1: 834
CASP-8: 841
GBP1: 2633
ASC: 29108"
  },
  {
    "caption": "AnnV-Glo assay from naïve or IFNγ-primed THP-1 ∆CASP-1 cells transfected with non-targeting control (CTRL), GBP1, AIM2, CASP-1 or CASP-8 siRNA and then untreated (UT) or transfected with STAg as indicated for 18 h. Area under the curve (AUC) from real-time assay plotted as mean ± SEM from n = 3 independent experiments. Schematic on right shows an overview of pathways leading to caspase-8 activation.",
    "ncbi_link": "AIM2: 9447
CASP-1: 834
CASP-8: 841
GBP1: 2633"
  },
  {
    "caption": "Propidium iodide (PI) uptake assay from MDMs transfected with non-targeting control (CTRL) or GBP1 siRNA and then left untreated (UT), treated with LPS or transfection reagent (Lipofectamine) only or transfected with LPS for 4 h. Area under the curve (AUC) from real-time assays plotted as mean ± SEM from n = 4 independent experiments. Schematic on right shows an overview of pathways leading to caspase-4 activation.",
    "ncbi_link": "GBP1: 2633"
  },
  {
    "caption": "B Western blot analysis confirming two Mettl5 KO clones by specific METTL5 antibody. α-TUBULIN was used as a loading control.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "C LC-MS/MS analysis of m6A/A levels in purified 18S rRNA and 28S rRNA from the WT and Mettl5 KO (KO-6B) mESCs.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "D PAGE gel electrophoresis showing the PCR amplification of the elongated and ligated products of SELECT method for detecting m6A1832 site and A1825 site (for input control) in 18S rRNA of WT and Mettl5 KO (KO-6B) mESCs, respectively.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "A,B Representative bright-filed (A) and AP staining (B) images of the WT and Mettl5 KO mESCs cultured in 2i/Lif medium. Scale bars represent 100 μm and 50 μm, respectively.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "C RT-qPCR analysis of the expression of pluripotency genes in WT and Mettl5 KO mESCs. Data are represented as mean ± SD from three biological replicates. Student's t test, two-tailed. ns, not significant; ***, P<0.001.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "D Western blot analysis of the expression of pluripotency markers in WT and Mettl5 KO mESCs. α-TUBULIN was used as a loading control.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "E Immunostaining analysis of the expression of pluripotency markers (POU5F1, SOX2 and NANOG) in WT and Mettl5 KO mESCs, respectively. DAPI (blue) was used as a nuclear counterstain. Scale bars represent 10 μm.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "C Immunostaining analysis of the expression of pluripotency marker POU5F1(left), endoderm marker FOXA2 (middle) and neuroectoderm marker NESTIN (right) in control and Mettl5 KO EBs at different time points, respectively. DAPI (blue) was used as a nuclear counterstain. Scale bars represent 100 μm. D Quantification of the percentages of positive cells shown in (C). Quantitative analysis was based on at least three independent experiments. Data are represented as mean ± SD. Student's t test, two-tailed. **, P < 0.01; ***, P<0.001. ",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "A Volcano plot depicting down-regulated (left) and up-regulated (right) genes in Mettl5 KO mESCs compared with WT mESCs in Ribo-seq. Significantly altered genes are defined as those ≥1.5-fold change and P value < 0.05 (shown in red dots). Blue dots represent genes with <1.5-fold change and P value < 0.05. Green dots represent genes with ≥1.5-fold change and P value ≥ 0.05. Black dots represent genes with ＜1.5-fold change and P value ≥ 0.05. P values were inferred from two-sided Wald tests (DESeq2) and P value adjustments were made for multiple comparisons. Examples of up- or down-regulated or non-significantly changed genes are annotated in the graph.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "B Track plot showing translational changes of Fbxw7 in Mettl5 KO mESCs compared with controls.",
    "ncbi_link": "Fbxw7: 50754
Mettl5: 75422"
  },
  {
    "caption": "C RT-qPCR analysis of Fbxw7 mRNA levels in WT and Mettl5 KO cells during the indicated time points course of EB induction. Data are represented as mean ± SD from three biological replicates. Student's t test, two-tailed. ns, not significant.",
    "ncbi_link": "Fbxw7: 50754
Mettl5: 75422"
  },
  {
    "caption": "D Western blot analysis showing FBXW7 expression in control and Mettl5 KO cells during the indicated time points of EB induction. GAPDH was used as a loading control.",
    "ncbi_link": "Mettl5: 75422"
  },
  {
    "caption": "E RT-qPCR analysis showing Fbxw7 mRNA levels in Day7 KO, KO+HA-MT5WT, and KO+HA-MT5Mut EBs. Data are represented as mean ± SD from three biological replicates. Student's t test, two-tailed. ns, not significant.",
    "ncbi_link": "HA: 
Fbxw7: 50754
MT5: 75422"
  },
  {
    "caption": "F Western blot analysis showing FBXW7 expression in Day7 KO, KO+HA-MT5WT, and KO+HA-MT5Mut EBs. GAPDH was used as a loading control.",
    "ncbi_link": "HA: 
MT5: 75422"
  },
  {
    "caption": "B Western blot analysis showing FBXW7 and c-MYC expression in control, Mettl5 KO (KO-6B) and KO+HA-MT5WT Day7 EBs, respectively. α-TUBULIN was used as a loading control.",
    "ncbi_link": "HA: 
Mettl5: 75422
MT5: 75422"
  },
  {
    "caption": "D RT-qPCR analysis of the expression of pluripotency and lineage-specific markers in Day7 FBXW7-induced EBs at the presence or absence of 10 ng/ml Dox. Data are represented as mean ± SD from three biological replicates. Student's t test, two-tailed. *, P < 0.05; **, P < 0.01; ***, P<0.001.",
    "ncbi_link": "FBXW7: 50754"
  },
  {
    "caption": "E Immunostaining analysis of the expression of pluripotency marker POU5F1, lineage-specific markers FOXA2, T and NESTIN in Day7 FBXW7-induced EBs at the presence or absence of 10 ng/ml Dox. Scale bars represent 100 μm.",
    "ncbi_link": "FBXW7: 50754"
  },
  {
    "caption": "G RT-qPCR analysis the expression of pluripotency and lineage-specific markers in Day7 c-MYC-induced EBs at the presence or absence of 10 ng/ml Dox. Data are represented as mean ± SD from three biological replicates. Student's t test, two-tailed. *, P < 0.05; **, P < 0.01; ***, P<0.001.",
    "ncbi_link": "c-MYC: 17869"
  },
  {
    "caption": "H Immunostaining analysis of the expression of pluripotency marker POU5F1, lineage-specific markers FOXA2, T and NESTIN in Day7 c-MYC-induced EBs at the presence or absence of 10 ng/ml Dox. Scale bars represent 100 μm.",
    "ncbi_link": "c-MYC: 17869"
  },
  {
    "caption": "(B) HEK293 and H1975 cells were transduced with full-length ACE2 by lentivirus. Protein extracts were immunoblotted with the indicated antibodies. O/E represents overexpression.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(C) GFP and full-length Spike co-transfected HEK293T cells were used as effector cells (293-S). HEK293/ACE2 (HEK293T-overexpressing ACE2) (left panel) or H1975/ACE2 (H1975-overexpressing ACE2) (right panel) cells were used as target cells. The 293-S cells were preincubated with normal human IgG or ACE2-Fc at 37°C for 1 hr. After that, the mixtures were added to target cells for 4 hr (cell-cell fusion) or 24 hr (syncytia formation). The fluorescent areas were measured by inverted fluorescence microscopy and Metamorph software (Metamorphosis). Scale bars equal to 50 µm. The white arrows indicate the cell-cell fusion or syncytia formation.",
    "ncbi_link": "GFP: 
ACE2: 59272
S: 43740568
Spike: 43740568"
  },
  {
    "caption": "(A) ACE2-Fc blocked the entry of Spike-expressing pseudotyped lentivirus into HEK293T-ACE2 and H1975-ACE2 cells. The relative luciferase activities, normalized to the only virus group, represent the efficiency of virus entry. MOI: Multiplicity of infection.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A) H1975 cells were transduced with full-length Spike by Lentiviral vector. Protein extracts were immunoblotted with the indicated antibodies. O/E represents overexpress.",
    "ncbi_link": "Spike: 43740568"
  },
  {
    "caption": "(H) Quantitative RT-PCR analysis of p16, p21 and DCR2 expression in IUGR-complicated and in normal placentas. Results were obtained from four human normal and four IUGR placentas. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) p < 0.001.",
    "ncbi_link": "p21: 1026
p16: 1029
DCR2: 8793"
  },
  {
    "caption": "DCE-MRI was performed on pregnant mice of WT, Cdkn1a, p53, Cdkn2a and Cdkn2a;p53 genotypes on day E14.5. Mice were injected i.v. with an albumin-labeled contrast agent (biotin-BSA-GdDTPA; 10 mg/mouse) and placental enhancement was monitored at 9.4T MRI for 60 min. (A) Representative T1-weighted image of a pregnant WT mouse and a selection of four different placentas (outlined by colored lines). ",
    "ncbi_link": "Cdkn1a: 12575
Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "DCE-MRI was performed on pregnant mice of WT, Cdkn1a, p53, Cdkn2a and Cdkn2a;p53 genotypes on day E14.5. Mice were injected i.v. with an albumin-labeled contrast agent (biotin-BSA-GdDTPA; 10 mg/mouse) and placental enhancement was monitored at 9.4T MRI for 60 min. (B) Representative SI dynamics of a single WT placenta (marked in A), following biotin-BSA-GdDTPA administered for 60 min. SI parameters of Initial Enhancement and Recovery are illustrated.",
    "ncbi_link": "Cdkn1a: 12575
Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "DCE-MRI was performed on pregnant mice of WT, Cdkn1a, p53, Cdkn2a and Cdkn2a;p53 genotypes on day E14.5. Mice were injected i.v. with an albumin-labeled contrast agent (biotin-BSA-GdDTPA; 10 mg/mouse) and placental enhancement was monitored at 9.4T MRI for 60 min. (C) Representative SI dynamics of a single WT placenta (marked in A) over time. Scale bar, 2.5 mm.",
    "ncbi_link": "Cdkn1a: 12575
Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "DCE-MRI was performed on pregnant mice of WT, Cdkn1a, p53, Cdkn2a and Cdkn2a;p53 genotypes on day E14.5. Mice were injected i.v. with an albumin-labeled contrast agent (biotin-BSA-GdDTPA; 10 mg/mouse) and placental enhancement was monitored at 9.4T MRI for 60 min. (D−G) Representative SI plots of Cdkn1a-/- (D), p53-/- (E), Cdkn2a-/- (F), and Cdkn2a-/-;p53-/- (G) placentas, compared to their WT or HET littermates. (H−I) Quantification of the SI Initial Enhancement (H) and SI Recovery (I) in WT, Cdkn1a-/-, p53-/-, Cdkn2a-/-, and Cdkn2a-/-;p53-/- placentas. MRI experiments were repeated at least three times for each murine genotype (n>=3 placental SI measurements from each genotype). Values are means +SEM; Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) p < 0.001.",
    "ncbi_link": "Cdkn1a: 12575
Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "Histological evaluation of H&E-stained sections in the labyrinth zone of murine Cdkn2a-/- (n=5 placentas), Cdkn2a-/-;p53-/- (n=5), p53-/- (n=4), and Cdkn1a-/- (n=3) placentas on day E14.5, compared to WT placentas (n=6). (A−E) The labyrinth zone of the WT (A) differs from those of Cdkn2a-/- (B) and Cdkn2a-/-;p53-/- (C) placentas. Black arrows indicate regular-sized nuclei in the WT placenta and polyploidy in the Cdkn2a-/- and Cdkn2a-/-;p53-/- placentas. Blue arrows indicate normal vasculature in the WT placenta and collapsed vasculature in the Cdkn2a-/- and Cdkn2a-/-;p53-/- placentas. Labyrinths of p53-/- (D) and Cdkn1a-/- (E) placentas did not differ from that of the WT placenta. L, labyrinth. Staining for each placenta was performed in triplicates. ",
    "ncbi_link": "Cdkn1a: 12575
Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "Histological evaluation of H&E-stained sections in the labyrinth zone of murine Cdkn2a-/- (n=5 placentas), Cdkn2a-/-;p53-/- (n=5), p53-/- (n=4), and Cdkn1a-/- (n=3) placentas on day E14.5, compared to WT placentas (n=6). (F−G) Ki67 immunostaining in the labyrinth zones of murine WT , p53-/- ,Cdkn2a-/-, and Cdkn2a-/-;p53-/- placentas, on day E14.5 (n=3 placentas from each genotype). (F) Representative images of Ki67 staining in the labyrinth zone are shown. Positive Ki67 trophoblast cells are indicated with arrows. L, labyrinth. (G) Proliferation scores (n=3 scores, derived from three placentas of each genotype) based on Ki67 staining show enhanced Ki67 expression in the placental labyrinths of Cdkn2a-/- and Cdkn2a-/-;p53-/- placentas relative to WT. Values are means +SEM of three scores for each genotype. *P < 0.05 by a one-tailed unpaired Student's t-test. Data information: Scale bars, 50 µm.",
    "ncbi_link": "Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "Histological evaluation of H&E-stained sections in the labyrinth zone of murine Cdkn2a-/- (n=5 placentas), Cdkn2a-/-;p53-/- (n=5) placentas on day E14.5, compared to WT placentas (n=6). (H) Representative images of SA-β-gal staining in the labyrinth zones of WT, Cdkn2a-/-, and Cdkn2a-/-;p53-/- placentas on day E14.5. (I) SA-β-gal activity, quantified by ImageJ sofware in Cdkn2a-/- and Cdkn2a-/-;p53-/- labyrinths, is significantly reduced relative to those in WT labyrinth (n>=7 fields of view from each genotype). Values are means + SEM. (***) p < 0.001 by a two-tailed unpaired Student's t-test. Data information: Scale bars, 50 µm. ",
    "ncbi_link": "Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "Human term placentas were dissected and cytotrophoblast cells were extracted and seeded. Quantitative RT-PCR analysis of expression of the cell cycle-related genes p16, p21 and CCNE1 Data information: Quantitative RT-PCR values are expressed as means +SEM. Results were obtained from trophoblast cultures derived from human placentas of four independent pregnancies. All RT-PCR experiments were performed in triplicates and repeated at least three times. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01.",
    "ncbi_link": "CCNE1: 898
p21: 1026
p16: 1029"
  },
  {
    "caption": "Human term placentas were dissected and cytotrophoblast cells were extracted and seeded. Quantitative RT-PCR analysis of expression of the syncytiotrophoblast markers GCM1, CGA and CGB (F). Data information: Quantitative RT-PCR values are expressed as means +SEM. Results were obtained from trophoblast cultures derived from human placentas of four independent pregnancies. All RT-PCR experiments were performed in triplicates and repeated at least three times. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01.",
    "ncbi_link": "CGA: 1081
CGB: 1114
GCM1: 8521"
  },
  {
    "caption": "Human term placentas were dissected and cytotrophoblast cells were extracted and seeded. Quantitative RT-PCR analysis of expression of the SASP components CCL2, CCL5, CCL8, IL6, IL1β, TGF-β and PDG-FC (H) in human primary trophoblast cultures on days 5 and 2. Data information: Quantitative RT-PCR values are expressed as means +SEM. Results were obtained from trophoblast cultures derived from human placentas of four independent pregnancies. All RT-PCR experiments were performed in triplicates and repeated at least three times. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01.",
    "ncbi_link": "CCL2: 6347
CCL5: 6352
CCL8: 6355
IL1β: 3553
IL6: 3569
PDG-FC: 56034
TGF-β: 7040"
  },
  {
    "caption": "Human term placentas were dissected and cytotrophoblast cells were extracted and seeded. Quantitative RT-PCR analysis of expression of the metalloproteases MMP2, MMP3 and MMP9 (I), in human primary trophoblast cultures on days 5 and 2. Data information: Quantitative RT-PCR values are expressed as means +SEM. Results were obtained from trophoblast cultures derived from human placentas of four independent pregnancies. All RT-PCR experiments were performed in triplicates and repeated at least three times. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01.",
    "ncbi_link": "MMP2: 4313
MMP3: 4314
MMP9: 4318"
  },
  {
    "caption": "(A) Immunoblot analysis of the indicated proteins in WT and Cdkn2a-/-;p53-/- placentas, on day E14.5 (two independent placentas out of four from each genotype are shown).",
    "ncbi_link": "Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "RT-PCR analysis of expression of Mmp2 in murine Cdkn2a-/-;p53-/- and in WT placentas on day E14.5 (n>=4 fields of view for each genotype). Values are means + SEM of at least three experimental repeats. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "ncbi_link": "Cdkn2a: 12578
Mmp2: 17390
p53: 22059"
  },
  {
    "caption": "RT-PCR analysis of expression of Mmp9 in murine Cdkn2a-/-;p53-/- and in WT placentas on day E14.5 (n>=4 fields of view for each genotype). Values are means + SEM of at least three experimental repeats. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "ncbi_link": "Cdkn2a: 12578
Mmp9: 17395
p53: 22059"
  },
  {
    "caption": "(D, E) Representative images (D) and quantification (E) of in-situ gelatin zymography of the labyrinth zone of murine WT and Cdkn2a-/-;p53-/- placentas on day E14.5. Scale bar, 50 μm. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "ncbi_link": "Cdkn2a: 12578
p53: 22059"
  },
  {
    "caption": "(I) Quantitative RT-PCR analysis of expression of MMP2, MMP9, IL6, and the JAK-STAT targets IFNAR1 and IFNAR2, in normal placentas and placentas from IUGR-complicated pregnancies. Results are from four human normal placentas and four placentas from IUGR-complicated pregnancies. Data information: Values are means + SEM of at least three experimental repeats. Statistical significance was determined by unpaired two-tailed Student's t-test (*) p < 0.05; (**) p < 0.01; (***) P<0.001.",
    "ncbi_link": "IFNAR1: 3454
IFNAR2: 3455
IL6: 3569
MMP2: 4313
MMP9: 4318"
  },
  {
    "caption": "(B) The transcriptional levels of DmATG1 in the third instar larvae were analysed by qRT-PCR. Ribosomal protein 49 (rp49) was used as an internal control; n=3. Bars indicate mean±s.d.",
    "ncbi_link": "DmATG1: 39454
rp49: 43573"
  },
  {
    "caption": "(D) Suppression of lipid vesicle aggregation in the fat body of dTOR mutants by reduced gene dosage of DmATG1. The fat body images of the second/early third instar larvae of denoted genotypes under fully fed conditions.",
    "ncbi_link": "DmATG1: 39454
dTOR: 47396"
  },
  {
    "caption": "(F) Quantitative analysis of cell and nuclear sizes in Fig 1E; n=5. Bars indicate mean±s.d. DmATG1, Drosophila Autophagy‐specific gene 1; dTOR, Drosophila TOR; qRT-PCR, quantitative real‐time reverse transcriptase-PCR.",
    "ncbi_link": "DmATG1: 39454
dTOR: 47396"
  },
  {
    "caption": "(B,C) Activation of dS6K in DmATG1 mutants. Phosphorylation of dS6K was examined by immunoblot analyses using phosphospecific dS6K T398 antibody in the third instar larvae or pupae of denoted genotypes. Tubulinimmunoblot was used as a loading control. Rheb expressing flies (hs>Rheb) were used as a positive control (C). hs>Rheb larvae were subjected to heat shock at 37°C for 1 h and then incubated at 30°C for 3 h before sample preparation to induce Rheb expression. For quantification, the levels of dS6K phosphorylation in each genotype were measured using Adobe Photoshop, and normalized to the tubulin levels. Results are expressed as a fold change compared with the wild‐type controls (w1118). DmATG1, Drosophila Autophagy‐specific gene 1; dS6k, Drosophila S6 kinase.",
    "ncbi_link": "DmATG1: 39454"
  },
  {
    "caption": "(C) HEK 293T cells transfected with control siRNA, ATG1α siRNA or ATG1β siRNA were deprived of nutrients for 90 min, and then the phosphorylation and protein levels of endogenous S6K (top two panels) and S6 (bottom two panels) were determined.",
    "ncbi_link": "ATG1α: 8408
ATG1β: 9706"
  },
  {
    "caption": "(D) HEK 293T cells transfected with control siRNA or ATG1α siRNA were deprived of nutrients for 90 min, and then replenished with DMEM for 30 min. The phosphorylation and protein levels of endogenous S6K were examined. For quantification, the levels of S6K Thr 389 phosphorylation were measured using Adobe Photoshop, and normalized to the S6K protein levels. Results are expressed as a fold change compared with the first indicated sample.",
    "ncbi_link": "ATG1α: 8408"
  },
  {
    "caption": "(E) HEK293T cells were transfected with control siRNA or ATG1α siRNA with pEGFP‐C1 (a transfection marker, green), and nutrient‐starved for 90 min, fixed and stained with phosphospecific S6 antibody (red). ATG1, Autophagy‐specific gene 1; HA, haemagglutinin; KI, ATG1α Lys 46 Ile (kinase‐dead) mutant; siRNA, short interfering RNA; S6K, S6 kinase; WT, wild type.",
    "ncbi_link": "ATG1α: 8408"
  },
  {
    "caption": "(A,B) HEK 293T cells were transfected with HA-Akt (A) or Myc-RSK (B), and/or Flag-ATG1α WT or KI plasmids. The immunoprecipitated Akt and RSK proteins were analysed by immunoblot using appropriate antibodies (top three panels). Flag (ATG1α) blots were completed from the same cell lysates (bottom panel).",
    "ncbi_link": "Akt: 207
RSK: 6195///6197///6196
ATG1α: 8408"
  },
  {
    "caption": "(C) HEK 293T cells were transfected with HA-S6K Thr 389 Glu mutant and/or Flag-ATG1α WT or KI. The immunoprecipitated S6K mutants were analysed by immunoblot using anti‐phosphospecific S6K Thr 229 (top panel) and HA (S6K) antibodies (middle panel). Flag (ATG1α) blot was completed from the same cell lysates (bottom panel). ATG1, Autophagy‐specific gene 1; EGF, epidermal growth factor; HA, haemagglutinin; KI, ATG1α Lys 46 Ile (kinase‐dead) mutant; RSK, ribosomal S6 kinase; WT, wild type.",
    "ncbi_link": "ATG1α: 8408"
  },
  {
    "caption": "b, Fluorescence microscopy of HeLa cells transfected with either IpaJ or VirA. The cis-Golgi (GM130, green) and F-actin (red) are shown. Scale bar, 10 µm.",
    "ncbi_link": "IpaJ: 876675
VirA: 876471"
  },
  {
    "caption": "b, Fluorescence microscopy of HeLa cells transfected with the indicated IpaJ mutants. The cis-Golgi (GM130, green) and F-actin (red) are shown. Scale bar, 10 µm.",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "c, IpaJ or its catalytic mutants were expressed from a galactose-inducible promoter (pGal413 vector) and assayed for a growth arrest phenotype on galactose or glucose (control) carbon source.",
    "ncbi_link": "Gal413: 
IpaJ: 876675"
  },
  {
    "caption": "e, Yeast strain harbouring a galactose-inducible IpaJ gene were transformed with a multi-copy vector containing the indicated genes. Yeast were assayed for a growth arrest phenotype on galactose or glucose (control) carbon source.",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "a-c, Mass spectra of purified ARF1-strep in untreated (a), IpaJ-treated (b) or IpaJ C64A-treated (c) cells, with the observed monoisotopic mass reported in daltons. *Observed 1 Da shift in molecular mass is accounted for in MS/MS data (Supplementary Fig. 7).",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "f, In-gel fluorescence assay (top panel) visualizing Alexa Fluor 647-labelled myristoylated ARF1-His isolated from bacteria either not expressing (lane 1) or expressing (lane 2) NMTp. Bacterial cell lysates treated with recombinant IpaJ or IpaJ C64A as indicated. The expression levels of ARF1-His were determined by Coomassie blue stain.",
    "ncbi_link": "IpaJ: 876675
NMTp: 850892"
  },
  {
    "caption": "g, In-gel fluorescence assay (top panel) visualizing Alexa Fluor 647-labelled myristoylated ARF1-strep purified from HeLa cell lysates left untreated or incubated with IpaJ or its catalytic mutant as indicated. The expressed amounts of ARF1-strep are shown (bottom panel).",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "h, In-gel fluorescence assay visualizing protein extracts isolated from HeLa cells incubated with azide myristic acid, azide palmitic acid or geranylgeranyl alcohol azide and subsequently labelled with Alexa Fluor 647 alkyne by click chemistry. Arrows indicate proteins that are proteolytically demyristoylated by IpaJ.",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "b, In-gel fluorescence assay showing myristoylated peptides of the indicated proteins in cells expressing IpaJ or catalytic mutant. The peptide-eGFP and IpaJ inputs are indicated. *Demyristoylation of GRASP65 and hVPS15 resulted in slower mobility of the resulting peptide, potentially owing to reduced mobility in SDS-polyacrylamide gel electrophoresis caused by proteolytic reaction.",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "c, In-gel fluorescence assay showing myristoylated ARF1 T31N mutant (a GDP-locked mutant) or ARF1 Q71L (a GTP-locked mutant) after in cells co-expressing IpaJ or catalytic mutants as indicated. Equal loading of ARF1 (middle panel) and IpaJ (lower panel) was determined by western blot analysis.",
    "ncbi_link": "ARF1: 375
IpaJ: 876675"
  },
  {
    "caption": "d, Fluorescence microscopy showing ARF1-mCherry and the Golgi apparatus (GM130) after cellular microinjection of recombinant IpaJ or IpaJ C64A, over the indicated period. Scale bar, 10 µm.",
    "ncbi_link": "IpaJ: 876675"
  },
  {
    "caption": "Detection of native and GFP-fused TgAtg8.Protein extracts corresponding to 107 tachyzoites from parental RHΔHX and transgenic GFP-TgAtg8 cell lines were separated by SDS-PAGE and analysed by Western blot using anti-TgAtg8 or anti-GFP antibodies. Overexpressed GFP-TgAtg8 and native TgAtg8 are indicated by arrows.",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "A. Protein extracts corresponding to tachyzoites incubated in the same starvation conditions as in Figure 2B were separated by urea SDS-PAGE and analysed with an anti-GFP antibody to detect TgAtg8 and the lipidated TgAtg8-PE form. GFP-TgAtg8 parasites extracts were analysed with anti GFP antibody (left), while parental cell line was analysed with anti-TgAtg8 antibody (right). Anti-ROP5 was used as a loading control.",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "B. Cell lysates from GFP-TgAtg8 parasites were subjected to a centrifugation at 100,000 g to separate the soluble fraction (high speed supernatant, HSS) from the membrane fraction (high speed pellet, HSP). The faster migrating form of GFP-TgAtg8 is exclusively present in the membrane fraction as revealed by Western blot analysis after urea SDS-PAGE using anti-GFP",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "D. GFP-TgAtg8-expressing parasites were grown in host cells in the presence of 3H-ethanolamine and then starved in HBSS for 8 hours, still in the presence of the radioactive PE precursor. Tachyzoites were then lysed and GFP-TgAtg8 was immunoprecipitated using anti-TgAtg8 antibody and analysed by urea SDS-PAGE. The immunoprecipitated forms of GFP-TgAtg8 were detected by Western blot using anti-GFP antibody and radioactive ethanolamine was found to be incorporated into immunoprecipitated GFP-TgAtg8, as detected by fluorography (3H-etn).",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "A. Fluorescence microscopy analysis of extracellular tachyzoites expressing GFP-TgAtg8 or its glycine mutant version, before or after induction of autophagy for 8 hours in HBSS. Autophagosomes are labelled by GFP-TgAtg8 in control parasites (arrowheads), but not by the glycine mutant version of the protein. B. Extracellular tachyzoites expressing GFP-TgAtg8 or its glycine mutant version were put to starve in HBSS medium for increased lengths of time and the proportions of cells displaying punctate or cytosolic GFP signals were assessed. Data are mean from n = 4 independent experiments ±SEM.",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "C. Protein extracts corresponding to tachyzoites expressing GFP-TgAtg8 and glycine mutant version incubated in HBSS for up to 8 hours, were separated by urea SDS-PAGE and analysed with an anti-GFP antibody to detect GFP-TgAtg8 and lipidated GFP-TgAtg8-PE forms. Anti-ROP5 was used as a loading control.",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "B. Fluorescence microscopy pictures of GFP-TgAtg8-expressing tachyzoites during their intracellular development and division. The arrowhead indicates the residual body made of maternal material left after endodyogeny.",
    "ncbi_link": "Atg8: 7900047"
  },
  {
    "caption": "A. Schematic representation of the strategy. Recombineered cosmid bearing chloramphenicol acetyl transferase (CAT) gene for selection of resistant parasites, flanked by homologous regions from TgAtg3, was used to replace endogenous genomic locus in the cell line expressing a regulatable extra copy of TgAtg3 (imyc-sTgAtg3). Mutants obtained after double homologous recombination events were selected with chloramphenicol. PCR amplifications and Southern blot strategy used for subsequent characterisation of the mutant are indicated in red and green, respectively. B. PCR verification of the removal of TgAtg3 in the mutant (imyc-sTgAtg3-ΔAtg3, A) compared to the parental cell line (imyc-sTgAtg3, B)",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "C. Southern blot verification of the TgAtg3 gene replacement. ∼4 µg of genomic DNA from mutant (A) and parental (B) tachyzoites were digested by HindIII/AvrII, transferred on a nylon membrane and probed with 32P-labeled 5′ and 3′ DNA probes located as schematised in A.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "A. The vector for the expression of the ATc-regulatable sTgAtg3 extra copy allows myc-epitope tagging of this protein. Anti-myc detection of myc-tagged TgAtg3 protein in intracellular parasites either without treatment with ATc, or with a continuous 2 days treatment with 1.5 µg/ml ATc, or after reinvasion following a continuous 4 days treatment. DIC: differential interference contrast.",
    "ncbi_link": "Atg3: B9Q737///7900125"
  },
  {
    "caption": "C. Western blot analysis following urea SDS-PAGE of TgAtg3-depleted parasites extracts, showing an absence of upregulation of the autophasome-bound TgAtg8-PE form. Anti-ROP5 was used as a loading control.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "A. Confluent monolayers of fibroblasts were infected either with extra copy-expressing imyc-sTgAtg3 parental cell line in the presence of ATc (a), imyc-sTgAtg3-ΔAtg3 mutant cell line without ATc (b), mutant cell line in the presence of ATc (c), or mutant cell line pre-incubated with ATc before start of the experiment and maintained in the presence of ATc. Plaques (arrowheads) resulting from the lysis of host cells due to the multiplication of the parasites are only visible when TgAtg3 is still expressed. B. Mean plaque area comparisons between fibroblast layers infected with controls and TgAtg3-depleted parasites (a, b, c: legend as in A). Plaques observed with the mutant in the presence of ATc were significantly smaller than with control cell lines (* p<0.005, Student's T test). Data are mean from n = 3 independent experiments ±SEM.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "C. Numbers of parasites per vacuole are significantly lower in TgAtg3-depleted cell line (pre-incubated for 4 days with ATc) compared with controls 24 or 48 hours post invasion. Data are mean from n = 3 independent experiments ±SEM.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "TgAtg3-depleted parasites show a defect in mitochondrion morphology.Mitochondrion labelled with specific antibodies (see results section) was found as a reduced structure, or even absent, in TgAtg3-depleted cell lines (middle series of micrographs, kept for 2 days in the presence of ATc or pre-incubated with ATc for 4 days before invasion, respectively). Parasites left to develop for two days in the presence of ATc to progressively extinguish the expression of TgAtg3 showed an accumulation of mitochondrial marker at the residual body. TgAtg3 depletion was verified by detecting myc-tagged regulatable extra-copy with specific antibody. TgAtg3-expressing cell line imyc-sTgAtg3cultivated in the presence of ATc for 4 days was used as a control for mitochondrial morphology (bottom). DNA was labelled with DAPI.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "Altered mitochondrial ultrastructure in TgAtg3-depleted tachyzoites observed by electron microscopy.Ultrathin section of a TgAtg3-depleted (3 days of ATc treatment) tachyzoite showing the dramatic alteration of the mitochondrion, where cristae remnants are still visible (arrows), but which is filled up with membranous profiles (arrowheads), whereas Golgi (G), apicoplast (A), rhoptries (R) and dense granule (D) look normal.",
    "ncbi_link": "Atg3: 7900125"
  },
  {
    "caption": "(B) SCPO, STIPO and STAPO after indicated siRNA treatment of GFP-LC3‐HEK cells incubated as in (A). Error bars represent s.e.m. Significance was determined using a two‐tailed paired t‐test compared with RISCfree (RF) in EL: SCPO siULK1, ***P=0.0002; siATG7, **P=0.0078; siNRBP2, **P=0.0088. STIPO siULK1, ***P0.0001; siATG7, **P=0.0060; siNRBP2, **P=0.0041. STAPO siULK1, ***P0.0001; siATG7, **P=0.0037; siNRBP2, **P=0.0028. The experiments were performed: RISCfree (n=5), siULK1 (n=5), siATG7 (n=3), siNRBP2 (n=3).",
    "ncbi_link": "ATG7: 10533
NRBP2: 340371
ULK1: 8408"
  },
  {
    "caption": "(D) Scatter plot of median SCPO Z‐scores from siRNA pools in the primary screen that met the minimum object count (OC) cutoff. Dashed lines represent approximate cutoff for 500 best increasers and decreasers. RP of known autophagy genes (ATG4C, ATG14, RB1CC1, ATG9A, ATG7) are given in Supplementary Table S2; AMBRA1 (FLJ20294), TBC1D25 (OATL1) and SH3GLB1 (BIF‐1) in Supplementary Table S1; LAMTOR2 has a RP=708.7 and RUBICON has a RP=1126.",
    "ncbi_link": "AMBRA1: 55626
ATG14: 22863
ATG4C: 84938
ATG7: 10533
ATG9A: 79065
RUBICON: 9711
LAMTOR2: 28956
RB1CC1: 9821
SH3GLB1: 51100
TBC1D25: 4943"
  },
  {
    "caption": "(C-E) STIPO results after incubation under different autophagy‐inducing conditions following (C) SCOC knockdown (D) SUPT5H knockdown and (E) WAC knockdown. siRNA‐treated cells were incubated for the indicated time in FL: full medium plus leupeptin; ES; EL: ES plus leupeptin; Torin: 250 nM Torin1 in FL; Resv: 128 μM Resveratrol in FL; LiCl: 10 mM LiCl in FM.",
    "ncbi_link": "SCOC: 60592
SUPT5H: 6829
WAC: 51322"
  },
  {
    "caption": "(C) Endogenous SCOC (green top, red bottom) partially colocalises with endogenous LC3 (red, top) and GFP-LC3 (green, bottom) in HEK293 and GFP-LC3‐HEK cells, respectively, after 2 h amino‐acid starvation. Boxed region is at higher magnification in merge panel on right. Scale bars=10 μm.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) SCOC is required for autophagy in HEK293 cells. Anti‐ULK1, ‐Actin and ‐LC3 blot after siRNA treatment in HEK293 cells in FM, ES or EL. Representative blot; quantification of LC3II/actin of averaged duplicates; error bars represent s.e.m. (n=3). Significance was determined using a two‐tailed paired t‐test: RF EL versus siSCOC‐03 EL, *P=0.0419.",
    "ncbi_link": "SCOC: 60592"
  },
  {
    "caption": "(B) SCOC is required for p62 degradation. p62 levels were determined by western blot (Supplementary Figure S5) after incubation in FM, ES for 2 or 4 h, or ES with BafilomycinA1 (ES+BAF) for 2 and 4 h. Quantification of averaged duplicates; error bars represent s.e.m. (n=3); RISCfree FM versus RISCfree ES 2 and 4 h, ***P>0.0001 and **0.0014, respectively.",
    "ncbi_link": "SCOC: 60592"
  },
  {
    "caption": "(C) SCOC-GFP and SCOC-myc levels are reduced by SCOC siRNA duplex‐03. Anti‐GFP, ‐Myc and ‐Actin blots of HEK293 cells after treatment with ULK1, RISCfree or SCOC siRNA and overexpression of GFP, SCOC-myc or SCOC-GFP.",
    "ncbi_link": "SCOC: 60592
ULK1: 8408"
  },
  {
    "caption": "(D) Overexpression of SCOC-myc increases autophagy. Anti‐Actin, ‐LC3 and ‐Myc blots of HEK293 cells after transfection of pcDNA or SCOC-myc. Representative blot; quantification of LC3II/actin of averaged duplicates; error bars represent s.e.m. (n=5). SCOC-myc EL versus pcDNA EL, *P=0.0215.",
    "ncbi_link": "SCOC: 60592"
  },
  {
    "caption": "(A) Knockdown of FEZ1 enhances LC3 lipidation but does not affect p62 degradation. Anti‐Actin and ‐LC3 blot after siRNA treatment in HEK293 cells. Quantification of LC3II/actin of averaged duplicates; error bars represent s.e.m. (n=3). Significance was determined using a two‐tailed paired t‐test: RISCfree ES versus siFEZ1‐01 ES, P=0.034. Quantification of p62/actin ( Supplementary Figure S5) performed as in Figure 4B; error bars represent s.e.m. (n=3); RISCfree FM versus RISCfree 2 and 4 hP>0.0001 and P=0.0014, respectively. qRT-PCR showing FEZ1 mRNA levels after indicated knockdown in GFP-LC3‐HEK cells (error bars represent s.d.).",
    "ncbi_link": "FEZ1: 9638
LC3: 440738///81631///84557"
  },
  {
    "caption": "(B) Overexpression of FEZ1 inhibits LC3 lipidation and p62 degradation. Anti‐Myc, ‐Actin and ‐LC3 blot after transfection with pcDNA or Myc-FEZ1 in HEK293 cells. Quantification of LC3II/actin; error bars represent s.e.m. (n=3); pcDNA ES versus Myc-FEZ1 ES, P=0.0318. Anti‐GFP, ‐Actin and ‐p62 blot after transfection with GFP or FEZ1-GFP and treatment with ES or ES plus Bafilomycin (EB) for 4 h. Quantification of averaged duplicates; error bars represent s.e.m. (n=3); GFP FM versus GFP ES, P=0.0077; GFP FM versus GFP EB, P=0.0212; GFP ES versus FEZ1-GFP ES, P=0.048.",
    "ncbi_link": "FEZ1: 9638"
  },
  {
    "caption": "(E) The FEZ1-SCOC interaction requires the evolutionary conserved residues L254 and L260 in the coiled‐coil domain of FEZ1 as demonstrated in GST‐pulldown assays with in vitro translated 35S‐labelled WT or mutant Myc‐FEZ1 and GST or GST‐SCOC. Autoradiographs of 10% input and bound proteins (top panels) and Coomassie blue‐stained gels of bead‐bound GST and GST‐SCOC proteins used (bottom panels).",
    "ncbi_link": "FEZ1: 9638"
  },
  {
    "caption": "(A) FEZ1 interacts with both the kinase domain (1-278) and the proline-serine rich spacer of ULK1 (279-828). GFP‐ or Myc‐tagged ULK1 fragments were in vitro translated with 35S‐methionine and subjected to GST‐pulldown assays using GST and GST-FEZ1 purified from E. coli (bottom). Bound proteins were detected by autoradiography following SDS-PAGE (top).",
    "ncbi_link": "FEZ1: 9638
ULK1: 8408"
  },
  {
    "caption": "(C) The FEZ1-GFP and Myc-ULK1 interaction is unaffected by amino‐acid starvation. Anti‐Myc and ‐GFP blots after HEK293 cells were co‐transfected with FEZ1-GFP and Myc-ULK1, incubated in FM or ES for 2 h, harvested and the complex was immunoprecipitated using anti‐GFP antibody.",
    "ncbi_link": "FEZ1: 9638
ULK1: 8408"
  },
  {
    "caption": "(D) BN-PAGE reveals SCOC and FEZ1 are in a complex. FEZ1-GFP, FLAG-SCOC and Myc-ULK1 wild type or kinase‐inactive ULK1K46I (ULK1KI) were co‐expressed in HEK293 cells. Anti‐GFP, ‐FLAG and ‐Myc western blots are shown for the BN-PAGE gel (top) or the SDS-PAGE gel (bottom). In GFP and FLAG western blots, two different exposures of the same BN-PAGE blot are shown spliced together.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(E) siRNA depletion of ULK1 does not affect the interaction of FEZ1 with SCOC. RF or ULK1 siRNA‐treated cells were co‐transfected with FEZ1-GFP and FLAG-SCOC, then incubated and immunoprecipitated as in (C). Western blot of lysates for ULK1, GFP and FLAG, and immunoprecipitates with GFP and FLAG antibodies.",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(F) siRNA depletion of SCOC reduces FEZ1-ULK1 complex. HEK293 cells treated with either SCOC or ULK1 siRNAs were transfected with FEZ1-GFP. FEZ1-GFP was detected with anti‐GFP in both BN-PAGE and SDS-PAGE. Endogenous ULK1 was detected with anti‐ULK1 antibody. Arrowheads indicate a FEZ1-GFP and endogenous ULK1 complex at 200 kDa and a larger MW complex >1236 kDa also detected in (D) in the triple transfection. The 200 KDa complex is sensitive to loss of SCOC and ULK1.",
    "ncbi_link": "SCOC: 60592
ULK1: 8408"
  },
  {
    "caption": "(A) SCOC interacts with UVRAG. HEK293 cells were transfected with FLAG-SCOC and Myc-UVRAG, lysed and incubated with anti‐FLAG (left) or anti‐Myc (right) antibodies. Co‐immunoprecipitation of Myc-UVRAG (left) and FLAG-SCOC (right) was confirmed using anti‐Myc and anti‐FLAG antibodies for western blotting. Asterisk in (A-C) and (D) indicates non‐specific bands.",
    "ncbi_link": "SCOC: 60592
UVRAG: 7405"
  },
  {
    "caption": "(B) Interaction of SCOC with UVRAG is unaffected by FEZ1-GFP. As in (A), co‐immunoprecipitation was preformed in HEK293 cells transfected with FLAG-SCOC, Myc-UVRAG and FEZ1-GFP. Myc-UVRAG was detected as in (A), FEZ1-GFP was detected with anti‐GFP antibody.",
    "ncbi_link": "FEZ1: 9638
SCOC: 60592
UVRAG: 7405"
  },
  {
    "caption": "(C) The SCOC and UVRAG interaction is reduced by starvation, and this reduction is inhibited by FEZ1-GFP. HEK293 cells were transfected as in (B) and 24 h later either treated with FM or ES for 2 h. FLAG-SCOC or Myc-UVRAG was immunoprecipitated with anti‐FLAG or anti‐Myc antibodies and the bound proteins were detected with anti‐Myc, ‐GFP or ‐FLAG antibodies by western blotting. Quantification of the amount of FLAG-SCOC co‐immunoprecipitated with Myc-UVRAG in FM or ES, without overexpressed FEZ1-GFP (left) or with overexpressed FEZ1-GFP (right). Significance was determined using a two‐tailed paired t‐test (n=3).",
    "ncbi_link": "FEZ1: 9638
UVRAG: 7405"
  },
  {
    "caption": "(D) FEZ1 interacts directly with endogenous UVRAG and is required for SCOC interaction. HEK293 cells were transfected with FEZ1-GFP, GFP or FLAG-SCOC alone or in combination. Top panel input, bottom panel immunoprecipitation with anti‐GFP or anti‐FLAG. Western blot for endogenous UVRAG, GFP-FEZ1 GFP or FLAG-SCOC as indicated. Arrowhead: endogenous UVRAG.",
    "ncbi_link": "FEZ1: 9638
SCOC: 60592"
  },
  {
    "caption": "(A) Depletion of endogenous WAC. Anti‐WAC and ‐Actin blot and WAC mRNA levels by qRT-PCR after treatment with RF or individual WAC siRNAs (W‐01 to W‐04) in HEK293 cells. qRT-PCR error bars represent standard deviation of triplicates (n=2).",
    "ncbi_link": "WAC: 51322"
  },
  {
    "caption": "(B) (B) WAC is required for autophagy. Anti‐ULK1, ‐WAC, ‐Actin and ‐LC3 blots after siRNA treatment in HEK293 cells and incubation in FM, ES or EL. Representative blot; quantification of LC3II/actin of averaged duplicates; error bars represent s.e.m. (n=3). Significance was determined using a two‐tailed paired t‐test: RF EL versus siWAC‐03 EL, **P=0.0079.",
    "ncbi_link": "WAC: 51322"
  },
  {
    "caption": "(C) p62 degradation requires WAC. Anti‐p62 and ‐Actin blot after siRNA treatment of GFP-LC3‐HEK cells in FM or ES for 2 h in duplicate. Bars represent p62/actin levels normalised to RF FM; quantification of p62/actin; error bars represent s.e.m. (n=3): RF FM versus RF ES, **P=0.0057; RF FM versus siWAC‐03 FM, **P=0.0025; RF ES versus siWAC‐03 ES, *P=0.0386.",
    "ncbi_link": "LC3: 440738///81631///84557
WAC: 51322"
  },
  {
    "caption": "(D) WAC depletion accelerates degradation of a UPS reporter. Anti‐p62, ‐GFP, ‐Actin, ‐LC3, ‐WAC and ‐Atg16 blots after siRNA treatment in UbG76V-YFP MelJuSo cells and incubation conditions FM, ES or FM with 10 μM MG132 (MG) for 2 h. Quantification of normalised average GFP intensity in FM of RISCfree compared with WAC‐03 siRNA treatment (n=3) and compared with ATG16 siRNA treatment (n=2). Error bars represent s.e.m.: RF FM versus siWAC‐03 FM, **P=0.0082.",
    "ncbi_link": "ATG16: 89849///55054
WAC: 51322"
  },
  {
    "caption": "(E) Soluble HttQ25-CFP degradation is increased after WAC depletion. Anti‐WAC, ‐Actin and ‐GFP blots after indicated siRNA treatment (siWAC duplexes ‐02, ‐03, ‐04) of HttPolyQ‐mutant HeLa cell lines and incubation conditions DMSO or DOX (Doxycyline) for 3 days. The insoluble fraction was obtained by pelleting the HttQ103 lysates (see Materials and methods). Quantification of normalised average HttQ25-CFP intensity in DMSO of RISCfree compared with WAC siRNA treatment; error bar represents s.e.m. (n=3): HttQ25-CFP/actin RF DMSO versus siWAC DMSO, *P=0.0350; soluble HttQ103-CFP/actin RF DMSO versus siWAC DMSO, *P=0.0380.",
    "ncbi_link": "Htt: 3064
WAC: 51322"
  },
  {
    "caption": "(A) Western blot analysis of FADD, FLIP and Caspase 8 at the TRAIL-R2 DISC in HCT116 cells treated with escalating doses (0-30nM) of caspase-8 siRNA for 48 hours. Samples were incubated with anti-TRAIL-R2 (AMG655) beads (4x) for 90 minutes prior to collection. A scrambled control siRNA (SC) was transfected (30nM) for comparison. (B) Quantification of Caspase 8 (p55, p43/41 and p26/24) and FLIP (FLIP(L), FLIP(S) and p43-FLIP) at the TRAIL-R2 DISC by densitometry and normalised to known protein standards (C) Ratio of Caspase-8:FLIP calculated from values presented in (B).",
    "ncbi_link": "caspase-8: 841"
  },
  {
    "caption": "(E) Western blot analysis of FLIP, Caspase 8, and FADD recruitment to the TRAIL-R2 DISC in PC3 cells stably expressing an empty vector (EV) or flag tagged FLIP L (FL) treated with 2.5µM MS-275 for 48 hours, followed by a 90 minute DISC IP. * modified form of FLIP, potentially mono-ubiquitinated p43-FLIP(L).",
    "ncbi_link": "flag: 
FLIP: 8837"
  },
  {
    "caption": "(A) Western Blot analysis of Caspase 8, Caspase 10, FLIP and FADD recruitment to the TRAIL-R2 DISC in procaspase 8 (WT) or procaspase 8 deficient (Null) A549 cells incubated with AMG655 beads (4x) for either 30, 60 or 180 minutes.",
    "ncbi_link": "procaspase 8: 841"
  },
  {
    "caption": "(B) Western blot analysis of the recruitment of FLIP, Caspase 8, Caspase 10 and FADD to the TRAIL-R2 DISC in HCT116 Parental, caspase 8 null (CASP8), caspase 10 null (CASP10) or CASP 8/10 cells treated with 4x AMG655 conjugated beads for 90 minutes.",
    "ncbi_link": "CASP10: 843
caspase 10: 843
CASP 8: 841
CASP8: 841
caspase 8: 841"
  },
  {
    "caption": "(D) AlphaScreen® assessment of the impact on the FLIP-FADD interaction of unstapled and stapled peptides corresponding to the FADD α1 helix.",
    "ncbi_link": "FADD: 8772"
  },
  {
    "caption": "(E) NanoBiT® assay to quantify FLIP/FADD interactions in a U2OS cell line stably expressing the NanoBiT® constructs, FLIP (LgBiT) and FADD (smBiT) following 48 hour silencing of FLIP, FADD, or caspase 8. Western blot analysis was used to confirm successful knockdown of target proteins by siRNA.",
    "ncbi_link": "caspase 8: 841
FLIP: 8837
FADD: 8772"
  },
  {
    "caption": "(F) NanoBiT® assay of HCT116 and U20S wild type (WT) and procaspase 8 null (Null) cells transiently co-transfected with FLIP (LgBiT) and FADD (SmBiT) NanoBiT® constructs for 24 hours. Construct expression was analysed by Western blotting.",
    "ncbi_link": "procaspase 8: 841"
  },
  {
    "caption": "(A) Western blot analysis of FLIP, Caspase 8 and FADD recruitment to the TRAIL-R2 DISC in U20S parental cells (EV) and 3 independent caspase 8 null clones (#1, #2, #3) after incubation with AMG655 conjugated beads for 30, 60 or 180 minutes.",
    "ncbi_link": "caspase 8: 841"
  },
  {
    "caption": "(E) Western blot analysis of FADD recruitment to the TRAIL-R2 DISC in HCT116 cells transiently transfected with an empty vector (EV), Flag-tagged FADD (WT), or Flag tagged FADD with point mutations at either Phe25 (F25A) or His9 (H9G). Western blotting analysis of the soluble unbound fraction was used to monitor transfection efficiency.",
    "ncbi_link": "Flag: 
FADD: 8772"
  },
  {
    "caption": "(F) NanoBiT® assay of U20S cells transiently co-transfected with caspase 8 (LgBiT) and either WT FADD smBiT or FADD (smBiT) constructs with a point mutation at either phenylalanine 25 (F25A) or histidine 9 (H9G) for 48 hours. Western blot analysis was used to assess the expression level of each construct.",
    "ncbi_link": "FADD: 8772"
  },
  {
    "caption": "(A) Western blot analysis of FLIP, caspase 8 and FADD recruitment to the TRAIL-R2 DISC in parental (WT) and CFLAR deficient (KO) HAP-1 cells treated with AMG655 conjugated beads for either 45 minutes (45'), 90 minutes (90'), 180 minutes (180'), 3 hours (3h), 6 hours (6h) or 9 hours (9h).",
    "ncbi_link": "CFLAR: 8837"
  },
  {
    "caption": "(C) Caspase-8 (i) and -3/7 (ii) activity assays and high content microscopy assessment of cell death (iii) in Parental (PAR) and FLIP knockout (CFLAR CRISPR) cells treated with escalating doses of isoleucine zipper TRAIL (IZ-TRAIL) for 6 hours.",
    "ncbi_link": "CRISPR: 
CFLAR: 12633
FLIP: 8837
TRAIL: 8794///8793///8797///8795///8743"
  },
  {
    "caption": "(D) Caspase-8 (i) and -3/7 (ii) activity assays in Parental (PAR) and FLIP knockout (CFLAR CRISPR) cells treated with escalating doses of isoleucine zipper TRAIL (IZ-TRAIL) for 24 hours. (iii) Flow cytometry assessment of cell death induction in Parental (PAR) and FLIP knockout (CFLAR CRISPR) cells treated with IZ-TRAIL for 24h.",
    "ncbi_link": "CRISPR: 
CFLAR: 12633
FLIP: 8837
TRAIL: 8794///8793///8797///8795///8743"
  },
  {
    "caption": "(E) Western Blot analysis of Parental (WT) and FLIP knockout (KO) HAP-1 cells treated with 10ng/mL IZ-TRAIL for 0, 3, 6 or 24 hours.",
    "ncbi_link": "FLIP: 8837
TRAIL: 8794///8793///8797///8795///8743"
  },
  {
    "caption": "(F) Cell viability assay of Parental (PAR) and FLIP knockout (CFLAR CRISPR cells) treated with an escalating dose (0-1000ng/mL) of IZ-TRAIL for 72 hours.",
    "ncbi_link": "CRISPR: 
CFLAR: 12633
FLIP: 8837
TRAIL: 8794///8793///8797///8795///8743"
  },
  {
    "caption": "(B) NanoBiT® assay performed on TRAIL-R2 DISC IPs (90') carried out in U20S Caspase-8 null cells co-transfected with wild-type or F114A FLIP-LgBiT fusion proteins and wild-type or F122A caspase-8-SmBiT fusion proteins.",
    "ncbi_link": "caspase-8: 841
FLIP: 8837"
  },
  {
    "caption": "(E) Western blot analysis of size exclusion chromatography experiments in which HCT116 cells transfected with Flag-tagged wild-type (WT) FLIP(S) were treated with 100ng/mL IZ-TRAIL for 3h prior to cell lysis and separation of low and high MW complexes using a size exclusion column. The fractions eluted at 2MDa and >2MDa are presented.",
    "ncbi_link": "Flag: 
FLIP: 8837
TRAIL: 8794///8793///8797///8795///8743"
  },
  {
    "caption": "D. Co-immunoprecipitation of FLAG-dmDis3l2 (bait) and GFP-Tailor full-length and truncations expressed in Drosophila S2cells. GFP-Nibbler (Nbr) served as negative control. Domain architecture of GFP-Tailor truncations are indicated.",
    "ncbi_link": "Tailor: 40847"
  },
  {
    "caption": "B. In vitro exoribonuclease assay using 5′ radiolabeled RNA substrate and immunopurified wild-type (WT) or catalytic mutant (CM) FLAG-dmDis3l2 (mutation indicated in Figure 1C), incubated for the indicated time and separated on a 15 % polyacrylamide gel followed by phosphorimaging. Quantification of degraded substrate in percent is indicated.C. Change in abundance of 256 different substrate RNAs as determined by high-throughput sequencing of substrates in experiment shown in (B).",
    "ncbi_link": "dmDis3l2: 38034"
  },
  {
    "caption": "A. RNA decay assay using synthetic, 5′ radiolabeled pre-miR-1003, immunopurified dmDis3l2 and wild-type (WT) or catalytic mutant (CM) Tailor. Reactions were incubated for the indicated time and separated by 15% denaturing polyacrylamide gel electrophoresis and subjected to phosphorimaging.B. Quantification of at least three independent replicates of experiment shown in A. Data represent mean SD. Half-life was determined by fitting data to single exponential (dmDis3l2 and dmDis3l2/TailorCM) or sigmoidal (dmDis3l2/TailorWT) reaction kinetics.",
    "ncbi_link": "miR-1003: 12798529
Tailor: 40847"
  },
  {
    "caption": "C. RNA decay assay using synthetic, 5′ radiolabeled pre-miR-1003 containing the indicated number or uridine residues at the 3′ end and immunopurified dmDis3l2.D. Quantification of three independent replicates of experiment shown in C. Data represent mean SD. Data were fit to single exponential reaction kinetics.E. Reaction kinetics (kobs) determined in D plotted against number of 3′ terminal uridine residues. Error of fit is shown as SEM.",
    "ncbi_link": "miR-1003: 12798529"
  },
  {
    "caption": "A and E. Western blot analysis of genetically modified Drosophila S2 cells. Unmodified S2 cells (wild-type, wt), or S2 cells depleted of Tailor (tailorko) by CRISPR/Cas9 or expressing FLAG-tagged Tailor (TailorOE) were analyzed. Antibodies are indicated. Note, that panels were assembled from two technical replicates of identical lysates (see source data).",
    "ncbi_link": "tailor: 40847"
  },
  {
    "caption": "A and E. Western blot analysis of genetically modified Drosophila S2 cells. Unmodified S2 cells (wild-type, wt), or S2 cells depleted of dmDis3l2 (dmDis3l2ko) by CRISPR/Cas9 or expressing FLAG-tagged catalytic mutant dmDis3l2 (dmDis3l2CM OE) were analyzed. Antibodies are indicated. Note, that panels were assembled from two technical replicates of identical lysates (see source data).",
    "ncbi_link": "dmDis3l2: 38034"
  },
  {
    "caption": "C. Northern hybridization experiment using total RNA from adult whole male flies using probes against 3′ trailer or mature tRNAAla(TGC). Wild-type flies (w1118), or flies bearing a homozygous frame-shift mutation in the first coding exon (dmDis3l2-/-) or a homozygous amino acid-exchange mutation in the catalytic site (dmDis3l2CM) in the endogenous dmdis3l2 locus in the same genetic background were used. Probes against 2S rRNA served as loading control.D. Quantification of four independent biological replicates of experiment shown in C. P-Value determined by Student's t-test.",
    "ncbi_link": "2S: 
dmDis3l2: 38034
dmdis3l2: 38034"
  },
  {
    "caption": "E. Exoribonuclease assay using immunopurified dmDis3l2 and in vitro transcribed, 5′ radiolabeled mature tRNA, containing a CCA modification or 3′ trailer-containing tRNA. Reactions were incubated for the indicated time and subjected to polyacrylamide gel electrophoresis and phosphorimaging.",
    "ncbi_link": "dmDis3l2: 38034"
  },
  {
    "caption": "Cyclin D3 was depleted using siRNA in Calu3 cells. Cells were infected 48h later with Delta SARS-CoV-2 at MOI 0.01. Cells were washed 4h post-infection and new media were added. Supernatants and cells were collected 48h later for western blot and TCID50. Uninfected cell lysates were used for western blot. Data information: Graphs represent average of n=4 (E) biological replicates. Statistical analysis was performed using one-way ANOVA with Dunnett's multiple comparisons test. NT, non-targeting control. ns, non-significant; ∗p < 0.1; ∗∗p < 0.01; ∗∗∗p < 0.001. Bars indicate mean with SD.",
    "ncbi_link": "Cyclin D3: 896"
  },
  {
    "caption": "A549 AT2  cells were depleted for D and A2 cyclins  (A) A representative western blot from lysates of uninfected knock-down cells.",
    "ncbi_link": "A2 cyclins: 890"
  },
  {
    "caption": "(E) A549 AT2  cells were transduced with VSV-G  pseudotyped Fucci containing lentiviral  particles and  VSV-G pseudotyped lentiviral  particles containing WT cyclin D3 or T283A mutant cyclin D3 (mutant not degraded by proteasome). Cells were infected 24h later and collected 48h post-infection for flow cytometry analysis of early S and western blot. n=2 biological replicates; Ordinary two-way ANOVA with Sidak's multiple comparisons test: ns, non-significant; ∗∗p < 0.01. Bars indicate mean with SD.",
    "ncbi_link": "cyclin D3: 896"
  },
  {
    "caption": "(A) 293T  cells were contransfected with HA  - cyclin D3 and Strep-tag-SARS-CoV-2 E or nsp9, and control plasmid (EV). Immunoprecipitation  was performed using anti-HA  antibody. The immunoprecipitates  were blotted  with anti-Strep, anti-HA, and cyclin D3 antibodies.",
    "ncbi_link": "HA: 
cyclin D3: 896
nsp9: 43740578"
  },
  {
    "caption": "(B) 293T  cells were contransfected with HA  - cyclin D3 and Strep-tag-SARS-CoV-2 E, M, both E and M or nsp9. Immunoprecipitation  was performed using anti-HA  antibody. The immunoprecipitates  were blotted  with anti-Strep, anti-HA  antibodies. WCL, whole cell lysate.",
    "ncbi_link": "HA: 
cyclin D3: 896"
  },
  {
    "caption": "(C-G) 293T GFP11  cells were transfected with Spike, and/or with Envelope, Membrane, and cyclin D3. 24h post-transfection cells were seeded at a 1:1 ratio with Vero-GFP10  cells and percentage of GFP+ve area (syncytia) were determined 18h later. S, Spike; E, Envelope; M, Membrane; D3, cyclin D3. (C,D) Representative images of GFP+ syncytia. Scale bars: 40μm. (E-G) Quantification of cell-to-cell fusion showing percentage of the GFP+ve area to the acquired total cell area. (E) n=4 biological replicates. (F,G) n = 4 biological replicates; technical triplicates shown; one-way ANOVA with Dunnett's multiple comparisons test: ns, non-significant; ∗∗∗∗p < 0.0001; ∗∗∗p < 0.001; ∗∗p < 0.01 . Bars indicate mean with SD.",
    "ncbi_link": "GFP10: 
GFP11: 
cyclin D3: 896
Envelope: 43740570
Membrane: 43740571
Spike: 43740568"
  },
  {
    "caption": " A) L7Cre rd1 retina expressing Lamplight-T2A-mCherry AAV. Anti-mCherry staining (white) was widespread (Left, scale bar = 500µm). Fluorescent cell bodies found in different focal planes consistent with expression in ganglion (Top Right, scale bar = 50µm) and bipolar cells (Bottom Right, scale bar = 50µm). ",
    "ncbi_link": "mCherry: 
Cre: 2777477"
  },
  {
    "caption": "(A) Immunoblotting for Dnmt1, Dmnt3a and Dmnt3b in the spinal cords of AR-97Q, AR-24Q, and wild-type mice. (B) Quantitative densitometry analysis indicated that Dnmt1 spinal cord level was up-regulated in AR-97Q mice (n = 3). Dnmt3a and Dnmt3b spinal cord level was not significantly different among wild-type, AR-24Q, and AR-97Q mice (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(C) Quantification of the Dnmts mRNA levels of the spinal cord in wild-type, AR-24Q, and AR-97Q mice using RT-qPCR (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(D and E) Representative immunohistochemical images depicting the expression of Dnmt1, Dmnt3a and Dmnt3b in the spinal cords of male AR-97Q, AR-24Q, and wild-type mice and quantification of the immunoreactivity for Dnmts (n = 25 neurons from three mice of each group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(F) Double-immunofluorescence staining for Dnmt1 and 1C2 in the spinal motor neurons of an AR-97Q mouse.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(G) Immunoblotting for Dnmt1 of the skeletal muscle of wild-type and AR-97Q mice. (H) Quantification of the signal intensity of Dnmt1 bands (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(A) Immunoblotting of NSC34 cells expressing AR-24Q or AR-97Q (NSC24Q and NSC97Q, respectively) that were treated with DHT for Dnmt1, Dnmt3a and Dnmt3b, and quantification of the signal intensities of bands corresponding to Dnmt1, Dnmt3a and Dnmt3b (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(B) Relative mRNA levels of Dnmt1 in NSC24Q and NSC97Q cells measured with RT-qPCR (n = 3).",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(D) RT-qPCR analysis of Dnmt1 in DHT-treated and -untreated NSC97Q cells (n = 3).",
    "ncbi_link": "Dnmt1: 13433"
  },
  {
    "caption": "(E, F) Quantitative assessment of cell viability changes due to the siRNA-mediated knock down of Dnmt1, Dnmt3a or Dnmt3b in NSC97Q cells with DHT (E) or without DHT (F) using the WST-8 assay (n = 3).",
    "ncbi_link": "Dnmt1: 13433
Dnmt3a: 13435
Dnmt3b: 13436"
  },
  {
    "caption": "(A-D) Grip power (A), body weight (B), rotarod performance (C) (Two-way ANOVA with Tukey's test) and survival rate (D) (Kaplan-Meier analysis and log-rank test) of AR-97Q mice treated with or without RG108 (DMSO, n =20; 0.5 mg/dL, n = 20; 2.0 mg/dL, n = 20). All parameters were significantly improved in AR-97Q mice treated with 2.0 mg/dL RG108 compared with those treated with DMSO: *P < 0.05 (grip); *P < 0.05 (body weight); *P < 0.05 (rotarod); and *P < 0.05 (survival).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(E) Representative photograph of a 13-week-old AR-97Q mouse treated with DMSO (left) and an age-matched AR-97Q mouse treated with 2.0 mg/dL RG108 (right). AR-97Q mouse medicated with RG108 maintained muscle volume and body size compared with DMSO-treated AR-97Q mouse of same age. The white compact masses (arrow) of mice head are the cement covering the surgical site.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(F,G) Immunoblots (F) and relative intensities (G) of the Dnmt1-immunoreactive bands of spinal cords from AR-97Q mice treated with or without RG108 (n = 3 per group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(H,I) Dnmt1 immunohistochemistry in spinal cord sections from AR-97Q mice treated with or without RG108 (n = 3 per group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(A) Immunohistochemistry of the spinal cords of AR-97Q mice treated with DMSO or RG108 for polyglutamine using a 1C2 antibody. (B) Quantification of 1C2-positive motor neurons in the spinal cords (n = 5 per group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(C) Immunoblotting of the spinal cords of AR-97Q mice treated with or without RG108 for AR. (D) Densitometric analyses to quantify AR accumulation in the spinal motor neurons of AR-97Q mice treated with DMSO or RG108 (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(E) Relative mRNA expression levels of human AR in AR-97Q mice spinal cord with or without RG108 treatment (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "Immunohistochemistry for ChAT in the spinal cord anterior horns of AR-97Q mice (n = 5 per group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "quantitative analysis of the neuron sizes in the spinal cord anterior horns of AR-97Q mice (n = 5 per group).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(H,I) Western blot analysis (H) and relative signal intensities (I) of the ChAT-immunoreactive bands of spinal cords from AR-97Q mice treated with or without RG108 (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(A) Immunoblotting of SH-SY5Y cells stably expressing AR-24Q (SH24Q) or AR-97Q (SH97Q) for Dnmt1, Dnmt3a and Dnmt3b. (B) Densitometry quantification showing that Dnmt1 level was up-regulated in SH97Q cells compared with SH24Q cells (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(F) The relative mRNA levels of CDC25B, GFRA3, NPY, HES5, SCTR, LEF1-AS1 and CABS1, normalized to beta-2 microglobulin, in DHT-treated SH24Q and SH97Q cells were measured using RT-qPCR (n = 3).",
    "ncbi_link": "beta-2 microglobulin: 
CABS1: 85438
CDC25B: 994
GFRA3: 2676
HES5: 388585
LEF1-AS1: 641518
NPY: 4852
SCTR: 6344"
  },
  {
    "caption": "(G) RT-qPCR analysis indicated the decrease of Hes5 mRNA level in DHT-treated SH97Q cells compared with DHT-untreated SH97Q cells (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(I) Hes5 immunoreactivity of spinal motor neurons in wild-type, AR-24Q, and AR-97Q mice (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(J) Hes5 mRNA levels in the spinal cords of wild-type, AR-24Q, and AR-97Q mice (n = 3).",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "DNA methylation levels of the HES5 promoter region of SH97Q cells treated with DHT and RG108.",
    "ncbi_link": "HES5: 388585"
  },
  {
    "caption": "HES5 mRNA levels of SH97Q cells treated with DHT and RG108.",
    "ncbi_link": "HES5: 388585"
  },
  {
    "caption": "DNA methylation levels of the Hes5 promoter region in DHT-treated NSC97Q cells treated with or without RG108.",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "mRNA levels of Hes5 (n = 3) in DHT-treated NSC97Q cells treated with or without RG108.",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(E) Hes5 mRNA levels in the spinal cords of AR-97Q mice treated with or without RG108 (n = 3).",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "(F, G) Hes5 immunoreactivity of spinal motor neurons in AR-97Q mice treated with or without RG108 (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(A) Viability of DHT-treated NSC97Q cells treated with Hes5 and control siRNA measured by the WST-8 assay (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(C) Quantitative cell viability analysis revealed that siRNA-mediated Hes5 knock down negated the therapeutic effect of RG108 in NSC97Q cells that were treated with DHT (n = 3), as determined by the WST-8 assay.",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "Cell viability measured with the WST-8 assay of DHT-treated NSC97Q cells transfected with a mock plasmid or the Hes5 vector (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "Cell viability measured with immunoblotting of DHT-treated NSC97Q cells transfected with a mock plasmid or the Hes5 vector (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(F) Quantification of LDH release from DHT-treated NSC97Q cells transfected with a mock plasmid or the Hes5 vector (n = 4).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(G) Immunoblots of DHT-administrated NSC97Q cells transfected with a mock plasmid or the Hes5 vector for AR. (H) AR aggregation as quantified by densitometry (n = 3).",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "(A) Immunoblots of NSC34 cells treated with Hes5 siRNA. (B) Quantification of protein levels of pSmad2, Smad2, phospho-IkBα and heat shock factor-1 (Hsf1) (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(C) siRNA-mediated knockdown of Hes5 down-regulated Hes5 protein level (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(E) Protein levels of Smad2, pSmad2, and Hes5 in NSC97Q cells transfected with Hes5 vector (n = 3).",
    "ncbi_link": "Hes5: 15208"
  },
  {
    "caption": "(F) Immunoblots of Smad2, pSmad2, and Hes5 in primary cortical neurons treated with lentiviral vector containing AR24Q and AR97Q (n = 3).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(G) Relative mRNA levels of Hes5 in primary cortical neurons expressing AR24Q and AR97Q (n = 3).",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "(H) Relative mRNA levels of Hes5 in primary motor neurons expressing AR24Q and AR97Q (n = 6).",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "(I) Western blots of Smad2, pSmad2, and Hes5 in primary cortical neurons expressing AR97Q treated with mock plasmid or Hes5-containing lentiviral vector.",
    "ncbi_link": "AR: 367
Hes5: 15208"
  },
  {
    "caption": "RAW264.7 macrophages were infected with Mtb WT or Mtb ΔRD1 for 24 h, Ca WT or Ca YL, and Lm WT or Lm Δhly for 60 min. (A) Levels of Rab8A and Rab8A pT72 phosphorylation were analysed by Western blot and quantified by densitometry. Data represent the mean ± SEM of three independent biological experiments. One-way ANOVA followed by Dunnett's test compared to WT strains. ns= non-significant; *p ≤0.05; **p ≤0.01.",
    "ncbi_link": "RD1: 
hly: 47223624"
  },
  {
    "caption": "(B) Recruitment of endogenous LRRK2 and EGFP-Rab8A to M. tuberculosis (Mtb) was visualised by confocal microscopy. Scale bar = 5 μm.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "(B) WT or LRRK2 KO macrophages were treated with 1 mM LLOMe for 30 min and Rab8A and Rab8A pT72 levels were analysed by Western blot.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "LRRK2 WT or LRRK2 KO macrophages were pre-treated or not with 1 μM GSK2578215A and treated with 1 mM LLOMe for 30 min. The number of LRRK2 per cell were monitored by immunofluorescence and high-content imaging. Scale bar = 10 μm. Data represent the mean ± SEM of three to four independent biological experiments. One-way ANOVA followed by Dunnett's test against the untreated WT control. ns=non-significant; **p≤0.01.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "LRRK2 WT or LRRK2 KO macrophages were pre-treated or not with 1 μM GSK2578215A and treated with 1 mM LLOMe for 30 min. The number of Rab8A positive vesicles per cell were monitored by immunofluorescence and high-content imaging. Scale bar = 10 μm. Data represent the mean ± SEM of three to four independent biological experiments. One-way ANOVA followed by Dunnett's test against the untreated WT control. ns=non-significant; **p≤0.01.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(A) RAW264.7 macrophages were electroporated with EGFP-Rab8A and treated with 1 mM LLOMe for 30 min. Intracellular distribution of Galectin-3, CHMP4B or LC3B was visualised by immunofluorescence. Scale bar = 5 μm.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "RAW264.7 WT, LRRK2 KO or Rab8A macrophages pre-treated with 1 μM GSK2578215A (GSK inh) were treated with 1 mM LLOMe for 30 min. CHMP4B vesicle numbers were analysed by immunofluorescence and high content imaging. Scale bar = 20 μm. Right panels show the quantification of number of CHMP4B positive vesicles per cell. Mean ± SEM of three independent biological experiments. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "LRRK2: 66725
Rab8A: 17274"
  },
  {
    "caption": "RAW264.7 WT, LRRK2 KO or Rab8A macrophages pre-treated with 1 μM GSK2578215A (GSK inh) were treated with 1 mM LLOMe for 30 min. Galectin-3 vesicle numbers were analysed by immunofluorescence and high content imaging. Scale bar = 20 μm. Right panels show the quantification of number of Galectin-3 positive vesicles per cell. Mean ± SEM of three independent biological experiments. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "LRRK2: 66725
Rab8A: 17274"
  },
  {
    "caption": "Live cell imaging of LysoTracker positive spots in WT, LRRK2 KO macrophages treated with 1 mM LLOMe, followed by lysosomal recovery after LLOMe wash-out. One representative experiment out of three shown. Differences between slopes in the LLOMe treatment window were estimated using linear regression.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "Live cell imaging of LysoTracker positive spots in WT, Rab8A KO macrophages treated with 1 mM LLOMe, followed by lysosomal recovery after LLOMe wash-out. One representative experiment out of three shown. Differences between slopes in the LLOMe treatment window were estimated using linear regression.",
    "ncbi_link": "Rab8A: 17274"
  },
  {
    "caption": "WT or LRRK2 KO RAW264.7 macrophages, RAW264.7 macrophages pre-treated with 1 μM GSK2578215A (GSK inh) and WT or Rab8A KO RAW264.7 macrophages were treated with 1 mM LLOMe for 30 min. LC3B positive vesicle numbers were analysed by immunofluorescence and high content imaging. Scale bar = 20 μm. Right panels show quantification of number of positive vesicles per cell. Data show the mean ± SEM of three to four biological replicates. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "LRRK2: 66725
Rab8A: 17274"
  },
  {
    "caption": "WT or LRRK2 KO RAW264.7 macrophages, RAW264.7 macrophages pre-treated with 1 μM GSK2578215A (GSK inh) and WT or Rab8A KO RAW264.7 macrophages were treated with 1 mM LLOMe for 30 min. ubiquitin K63 positive vesicle numbers were analysed by immunofluorescence and high content imaging. Scale bar = 20 μm. Right panels show quantification of number of positive vesicles per cell. Data show the mean ± SEM of three to four biological replicates. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "LRRK2: 66725
Rab8A: 17274"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Mtb for 24 h, Galectin-3 and LC3B recruitment was analysed by immunofluorescence and high content imaging. Scale bar = 10 μm. Data show the mean ± SEM of two to three experiments. ns=non-significant, *p≤0.05 by Student's t-test.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Ca for 60 min Galectin-3 and LC3B recruitment was analysed by immunofluorescence and high content imaging. Scale bar = 10 μm. Data show the mean ± SEM of two to three experiments. ns=non-significant, *p≤0.05 by Student's t-test.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Lm for 60 min. Galectin-3 and LC3B recruitment was analysed by immunofluorescence and high content imaging. Scale bar = 10 μm. Data show the mean ± SEM of two to three experiments. ns=non-significant, *p≤0.05 by Student's t-test.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Mtb WT or Mtb ΔRD1 Growth measured for 72 h Data show the mean ± SEM of three independent biological experiments. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "RD1: 
LRRK2: 66725"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Ca WT or Ca YL Growth measured for 2 h. Data show the mean ± SEM of three independent biological experiments. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "WT and LRRK2 KO RAW264.7 macrophages were infected with Lm WT or Lm Δhly. Growth measured for 2 h. Data show the mean ± SEM of three independent biological experiments. ns=non-significant, *p≤0.05, **p≤0.01 by One-way ANOVA followed by Sidak's multiple comparisons test.",
    "ncbi_link": "hly: 47223624
LRRK2: 66725"
  },
  {
    "caption": "Monocyte-derived macrophages from healthy controls and PD patients carrying the G2019S (Donor 2-3) or R1441C (Donor 1) LRRK2 mutation were pre-treated with 0.1 μM MLi-2 and treated with 1 mM LLOMe for 30 min. (A) Rab8A and Rab8A pT72 levels were analysed by Western blot. ",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "C Relative mRNA expression of Zeb1, Acp5, and Ctsk during the differentiation from BMDMs to osteoclasts in culture (n = 3).",
    "ncbi_link": "Acp5: 11433
Ctsk: 13038
Zeb1: 21417"
  },
  {
    "caption": "A Representative nanoCT of sagittal sections of femurs with 3D reconstruction of the distal femur trabeculae of 3-month-old wild-type and Zeb1ΔM/ΔM male mice are shown. The genotype of Zeb1+/+, Zeb1f/+, Zebf/f mice is defined as "wild-type" control. Scale bar, 500 μm. B Quantification of BV/TV, Tb.Th, Tb.N, and Tb.Sp as determined by nanoCT in 3-month-old wild-type and Zeb1ΔM/ΔM male mice (n = 8). C",
    "ncbi_link": "Zeb: 21417
Zeb1: 21417"
  },
  {
    "caption": "C H&E and TRAP staining of the distal femurs of 3-month-old male wild-type and Zeb1ΔM/ΔM mice. Scale bar, 200 μm. D Quantification of osteoclast number per bone surface (N.Oc/BS) and eroded surface per bone surface (ES/BS), as well as serum CTX-I and OCN levels in 3-month-old wild-type and Zeb1ΔM/ΔM male mice are shown (n = 6). E",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "E Golden's trichrome staining illuminating howship's lacunae (arrow) of the distal femurs of 3-month-old male wild-type and Zeb1ΔM/ΔM mice were performed along with double-calcein bone labeling and confocal imaging to assess bone formation. Scale bar, 10 μm. F Quantification of MAR and BFR as assessed in 3-month-old male wild-type and Zeb1ΔM/ΔM mice (n = 6). D",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "B Zeb1, NFATc1, c-Fos, c-Src, β3 integrin, Mmp9, Mmp14, and Ctsk expression as assessed by Western blot in wild-type and Zeb1ΔM/ΔM BMDMs during osteoclast differentiation (n = 3).",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "H, I After a 6-day culture atop bone slice, phalloidin staining (red) was performed in wild-type versus Zeb1ΔM/ΔM osteoclasts (I), and actin ring area per cell quantified (H). Scale bar, 20 μm.",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "E Relative mRNA expression of Ckmt1 in BMDMs and osteoclasts generated from wild-type or Zeb1ΔM/ΔM mice.",
    "ncbi_link": "Ckmt1: 12716
Zeb1: 21417"
  },
  {
    "caption": "F MtCK1, Ckb, VDAC, and Tomm20 expression as assessed by Western blot in BMDMs and osteoclasts generated from wild-type or Zeb1ΔM/ΔM mice (n = 3).",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "H MtCK1 (green) immunofluorescence of wild-type and Zeb1ΔM/ΔM osteoclasts. Scale bar, 20 μ",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "A Phosphocreatine (PCr) and creatine (Cr) level, as well as PCr/Cr ratio of wild-type or Zeb1ΔM/ΔM osteoclasts cultured atop plastic substrata as determined by LC/MS analysis (n = 3).",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "B, C Oxygen consumption rate (OCR) profile plot (B) and mitochondrial function parameters (C) analyzed by XF Cell Mito Stress Assay in osteoclasts from wild-type or Zeb1ΔM/ΔM mice after sequential treatment of compounds modulating mitochondrial function (n = 4).",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "C Wild-type BMDMs were transduced with either a mock vector, wild-type human MtCK1, or a catalytically-inactive MtCK1C316G mutant expression vector, differentiated into osteoclasts, and cell lysates collected for MtCK1, Ckb, Tomm20, VDAC, Zeb1, c-Src, and Ctsk immunoblotting (n = 3).",
    "ncbi_link": "MtCK1: 548596"
  },
  {
    "caption": "E PCr/Cr ratio of mock vector-, MtCK1-, or MtCK1C316G-transduced wild-type osteoclasts cultured on plastic substrata as determined by LC/MS analysis (n = 3).",
    "ncbi_link": "MtCK1: 548596"
  },
  {
    "caption": "OCR profile plot (H) analyzed by XF Cell Mito Stress Assay in mock vector-, MtCK1-, or MtCK1C316G-transduced wild-type osteoclasts after sequential treatment of compounds modulating mitochondrial function (n = 4).",
    "ncbi_link": "MtCK1: 548596"
  },
  {
    "caption": "J, K Mock vector-, MtCK1-, or MtCK1C316G-transduced wild-type pre-osteoclasts were cultured atop bone slices for 3 days, stained with phalloidin (red). Osteoclasts were removed and resorption pits visualized by WGA-DAB staining (J). The actin ring area per cell and resorption pit area were quantified (K; n = 6). Scale bar, upper 20 μm, lower 100 μm.",
    "ncbi_link": "MtCK1: 548596"
  },
  {
    "caption": "A, B Human monocyte-derived macrophages (hMDMs) were transfected with either shCTRL or siRNA targeting ZEB1, differentiated into osteoclasts, and relative mRNA expression of CKMT1 (A) and mitochondrial creatine kinase activity determined (B; n = 3).",
    "ncbi_link": "CKMT1: 548596
ZEB1: 6935"
  },
  {
    "caption": "F Mitochondrial function parameters analyzed by XF Cell Mito Stress Assay in non-targeting siCTRL- or siZEB1-transfected osteoclasts after sequential treatment of compounds modulating mitochondrial function (n = 4).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "G, H siCTRL- or siZEB1-transfected human osteoclasts were cultured atop bone slices for 6 days and stained with phalloidin (red). Osteoclasts were removed and resorption pits visualized by WGA-DAB staining (G). Scale bar, upper 20 μm, lower 100 μm. The actin ring area per cell, resorption pit area, and the number of TRAP+ MNCs were quantified (H; n = 6).",
    "ncbi_link": "ZEB1: 6935"
  },
  {
    "caption": "I-L Calvaria isolated from wild-type and Zeb1ΔM/ΔM mice were cultured in the presence or absence of 200 μM cyclocreatine, and stained for phalloidin (red) and Vpp3 (green) (I). Scale bar, 10 μm. The TRAP activity of whole cell lysates, actin ring area per cell, and supernatant CTX-I were quantified (J-L; n = 6).",
    "ncbi_link": "Zeb1: 21417"
  },
  {
    "caption": "(D, E) Isolated vaginal LCs  were stimulated O/N with P. timonensis (PT) followed by infection  with VSV-g-BlaM-Vpr  fusion (positive control) and  NL4.3Bal-BlaM-Vpr  fusion. Figure shows representative plots (D) and pooled data (E, n = 3) of viral fusion as determined by   β-lactamase-Vpr (BlaM-Vpr) activity. Data information: Symbols represent independent donors (mean of duplicates). Data are mean ± SD. Two-tailed t-test, **p  < 0.01, ***p <0.001, and ****p < 0.0001.",
    "ncbi_link": "BlaM: 
β-lactamase: 
Vpr: 155807"
  },
  {
    "caption": "E & F) cryotomogram slices, STAs, and schematics of H. pylori fliP* cells showing the MS-complex (E) and the C-complex (F). The two novel cytoplasmic rings are highlighted with light and dark green arrows in the STA panel. White arrows in (A-F) point to the particles.",
    "ncbi_link": "fliP: 66521904"
  },
  {
    "caption": "G & H) central slices through the STAs of the MS-complexes of the motile H. pylori (G)and H. pylori FliP* mutant (H) with the diameters of their various constituent rings indicated.",
    "ncbi_link": "FliP: 66521904"
  },
  {
    "caption": "A-G) Slices through electron cryotomograms (left panels), central slices of subtomogram averages (middle panels), and schematic representations (right panels) of the MS- and C-complexes (white arrows on the slices) of different mutants in H. pylori fliP*. Light and dark green arrows in (A and D) point to the ~53-nm and ~67-nm cytoplasmic rings. Scale bars for cryotomogram slices are 50 nm, and 20 nm for STAs. Empty panels indicate that there were not enough examples to produce a STA.",
    "ncbi_link": "fliP: 66521904"
  },
  {
    "caption": "A Specific CD8+ T-cell (OT-I) proliferation in response to immature BMDCs incubated with fdOVA, fdOVA/sc-αDEC or OVA257-264 peptide chemically coupled to anti-DEC-205 antibody (NLDC:pOVA). Percentage of CFSE-labeled proliferating T cells was evaluated on CD8+-gated cells after 72 h of DC:T co-culture. The mean ±SD of three independent experiments is reported.",
    "ncbi_link": "OVA: 
DEC: 17076"
  },
  {
    "caption": "B Proliferation of adoptively transferred OT-I T cells in C57BL/6mice (n = 3/group) immunized with vehicle (PBS), NLDC:pOVA, NLDC:pOVA plus CpG, fd, fd/sc-αDEC or LPS-free ovalbuminprotein. Percentage of CFSE-labeled proliferating OT-I T cells was evaluated after three days on Vα2+CD8+-gated cells. The mean ± SD of two independent experiments is reported. Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "DEC: 17076"
  },
  {
    "caption": "D-F IL-6 (D), IL-18 (E) and IFN-α (F) release in supernatants of BMDCs obtained from C57BL/6 mice. Supernatants of BMDCs incubated with NLDC145 antibody, wild-type phage particles (fdWT) or scFv αDEC-205 phage particles (fdsc-αDEC) for 20 h were analyzed by ELISA for cytokine production. Unstimulated culture (medium) and LPS-treated culture were, respectively, used as negative and positive controls. Bars represent mean values ± SD. Cumulative results are shown of three independent experiments assayed in duplicate. Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "DEC: 17076
DEC-205: 17076"
  },
  {
    "caption": "IL-6 was evaluated by ELISA in supernatants of BMDCs obtained from C57BL6, MYD88, TLR9 or TLR4 KO mice and incubated for 20 h with wild-type or fdsc-αDEC phage particles. LPS or CpG-ODN were used as controls. IL-6 release from DCs derived from MyD88−/−mice was totally abolished and dramatically reduced in DCs derived from Tlr9−/−mice, but not affected in Tlr4−/− DCs. Bars represent mean values ± SD. Cumulative results are shown of three independent experiments assayed in duplicate. Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "DEC: 17076
MYD88: 17874
MyD88: 17874
TLR4: 21898
Tlr4: 21898
TLR9: 81897
Tlr9: 81897"
  },
  {
    "caption": "IFN-α release evaluated by ELISA in supernatants of BMDCs obtained from C57BL/6 or KO mice and incubated for 20 h with wild-type or fdsc-αDEC phage particles. LPS or CpG-ODN were used as controls. MyD88−/− and Tlr9−/− but not Tlr4−/− BMDCs were unable to produce IFN-α after fdsc-αDEC stimulation. Bars represent mean values ± SD. Cumulative results are shown of three independent experiments assayed in duplicate. Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "DEC: 17076
MyD88: 17874
Tlr4: 21898
Tlr9: 81897"
  },
  {
    "caption": "IL-6 mRNA expression by DC cells. C57BL/6, MyD88−/− and Tlr9−/− mice were inoculated intraperitoneally with fdWT or fdsc-αDEC bacteriophages or, as a control, with LPS. Mice were sacrificed 2 h later, and purified spleen dendritic cells were analyzed for IL-6 mRNA levels by quantitative real-time PCR. Bars represent the mean fold increase ± SD. The experiments were performed three times (n = 2 per group). Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "IL-6: 16193
DEC: 17076
MyD88: 17874
Tlr9: 81897"
  },
  {
    "caption": "Proliferation of OT-ICD8+T cells after 72 h of co-culture with 1 × 104DCs isolated from C57BL/6mice or from MyD88−/− or Tlr9−/− transgenic mice previously injected with fd/sc-αDECbacteriophage particles. The panel shows the percentage of divided, CFSE-low OT-ICD8+T cells. As a control, the proliferation of OT-ICD8+T cells co-cultured with DCs isolated from non-immunized (NI) C57BL/6mice is reported. The mean ± SD of two independent experiments with n = 3 per group is reported. Comparative analyses were performed using Student's t-test for unpaired samples.",
    "ncbi_link": "DEC: 17076
MyD88: 17874
Tlr9: 81897"
  },
  {
    "caption": "IFN-γ production by OT-I CD8+ T cells co-cultured for 12 h in the presence of 3.3 × 103 DCs isolated from C57BL/6 mice or MyD88−/− and Tlr9−/− transgenic mice injected as in (D).",
    "ncbi_link": "MyD88: 17874
Tlr9: 81897"
  },
  {
    "caption": "BMDCs were incubated with TRITC-conjugated fdWT (A, C) or fdsc-αDECbacteriophages (B, D) for 6 h. Cells were then fixed, permeabilized, immunostained with anti-EEA-1 (A, B) or anti-LAMP-1 (C, D) (green) antibody and analyzed by confocalmicroscopy. Representative images are shown. Numbers at the bottom of the right panels indicate the percentage of EEA-1 (A, B) or LAMP-1 (C, D) bacteriophage co-localization (mean values ± SD, N = 2, n = 100). Scale bars, 10 mm. White arrows indicate LAMP-1-positive structures that also are positive or contain fdsc-αDEC or fdWT bacteriophages.",
    "ncbi_link": "DEC: 17076"
  },
  {
    "caption": "A-D BMDCs from C57BL/6mice were stably transduced with YFP-tagged TLR9. Cells grown on coverslips were then incubated with TRITC-conjugated wild-type (A, B) or fdsc-αDEC (C, D) bacteriophages for 6 h. Cells were then washed, fixed and analyzed by confocal microscopy. Nuclei were counterstained with Hoechst. (B, D) are enlargements of a single cell. Representative images are shown. Numbers at bottom of right panels indicate the percentage of TLR9bacteriophage co-localization (mean values ± SD, N = 2, n = 100). Scale bars, 10 mm.",
    "ncbi_link": "DEC: 17076
TLR9: 81897"
  },
  {
    "caption": " [A] Plants grown with 0.05 MS and GMVs (G 0.05) showed hyper-induction of IPS1 and PS2 gene expression in both shoots and roots, compared to plants grown with 0.05 MS alone (C 0.05). Values are means ± SE of three biological replicates. ",
    "ncbi_link": "IPS1: 820152
PS2: 843632"
  },
  {
    "caption": "Supplementation of Pi to the nutrient-deficient plants (0.05 + Pi) significantly reduced hyper-induction of IPS1 gene expression (D) triggered by GMVs. Data information: The boxplots show representative data from three independent experiments (n=12). Whiskers represent the min to max data range, the median is represented by the central horizontal line. The upper and lower limits of the box outline represent the first and third quartile. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test within each group of the same DAT.",
    "ncbi_link": "IPS1: 820152"
  },
  {
    "caption": " [G] The Arabidopsis phr1phl1 mutant showed substantially decreased growth-promotion, compared to the wild type plants. Data information: The boxplots show representative data from three independent experiments (n=12). Whiskers represent the min to max data range, the median is represented by the central horizontal line. The upper and lower limits of the box outline represent the first and third quartile. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test within each group of the same DAT.",
    "ncbi_link": "phl1: 833026
phr1: 828979"
  },
  {
    "caption": "Compared to the wild type plants, phr1phl1 showed substantially decreased anthocyanin hyper accumulation (D) triggered by DA. Data information: The boxplots show representative data from three independent experiments (n=6). Whiskers represent the min to max data range, the median is represented by the central horizontal line. The upper and lower limits of the box outline represent the first and third quartile. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test.",
    "ncbi_link": "phl1: 833026
phr1: 828979"
  },
  {
    "caption": "Compared to the wild type plants, phr1phl1 showed substantially decreased PSR gene hyper induction (E) triggered by DA. Data information: qPCR results show values of means ± SE of two biological replicates. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test.",
    "ncbi_link": "phl1: 833026
phr1: 828979"
  },
  {
    "caption": "Exogenous application of SA mimics DA-induced IPS1 gene induction (E) patterns in Pi-deficient plants. Data information: qPCR results show values of means ± SE (n=3), two biological replicates were analyzed with similar results. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test.",
    "ncbi_link": "IPS1: 820152"
  },
  {
    "caption": "Compared to the wild type plants, the NahG transgenic plants showed altered responses to DA under Pi-deficiency condition, as shown by plant images (F)",
    "ncbi_link": "NahG: "
  },
  {
    "caption": "Compared to the wild type plants, the NahG transgenic plants showed altered responses to DA under Pi-deficiency condition and quantification of anthocyanin accumulation levels (G). Data information: The boxplots show representative data from three independent experiments (n=6). Whiskers represent the min to max data range, the median is represented by the central horizontal line. The upper and lower limits of the box outline represent the first and third quartile. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test.",
    "ncbi_link": "NahG: "
  },
  {
    "caption": " [C] DA induces gene expression of AZI1 in Arabidopsis. Different letters denote significantly different means at p < 0.05, Tukey's multiple comparison test within each group. Bar indicates mean ± SE (n=3), two biological replicates were analyzed with similar results. ",
    "ncbi_link": "AZI1: 826859"
  },
  {
    "caption": " [F] Root colonization of GB03 in wild type Arabidopsis (Col-0) and the mutants/transgenic lines npr1, NahG, and rbohd. *** p < 0.001compared with Col-0 without DA treatment, n= 9 biological replicates, student t-test. ",
    "ncbi_link": "NahG: 
npr1: 842733
rbohd: 834842"
  },
  {
    "caption": "(A-D) A. castellanii was infected (MOI 5) with L. pneumophila JR32 producing (A) GFP under the control of PflaA (Ptac-mCherry-PflaA-gfp) and mCherry constitutively, (B) GFP under the control of PralF (PralF-gfp) and stained with DAPI, (C) GFP under the control of PsidC (PsidC-gfp) and stained with DAPI, or (D) Timer constitutively (pNP107). The infected amoebae were fixed at different time points post-infection, analyzed by confocal microscopy and 3D reconstructed (scale bars: 5 µm). Motile and virulent bacteria (GFP-positive) emerge at the colony cluster periphery only after bacterial replication has ceased (red fluorescent Timer).",
    "ncbi_link": "flaA: 
gfp: 
mCherry: 
tac: 
ralF: 57035941
sidC: 57036508"
  },
  {
    "caption": "(A) L. pneumophila subpopulation proteomics. A. castellanii was infected (MOI 5, 42 h) with L. pneumophila JR32 (Ptac-mCherry-PflaA-gfp). After cell lysis, released intracellular bacteria were sorted by flow cytometry in mCherry-positive/GFP-negative and mCherry-positive/GFP-positive L. pneumophila subpopulations, and their proteome was determined and compared. Protein abundance in each subset is depicted as a volcano plot. Proteins enriched in the GFP-producing subpopulation have a positive log2 ratio (q-value).",
    "ncbi_link": "flaA: 
gfp: 
mCherry: 
tac: "
  },
  {
    "caption": "(D, E) Expression of select L. pneumophila genes in amoebae. A. castellanii was infected (MOI 5; 6 h and 48 h) with L. pneumophila JR32 harboring reporter constructs for (D) PfleQ-mCherry-PflaA-gfp or (E) PlegC8-mCherry-PflaA-gfp, respectively. The infected amoebae were fixed and imaged by confocal microscopy (scale bars: 5 µm).",
    "ncbi_link": "gfp: 
mCherry: 
flaA: 
fleQ: 
legC8: 57036860"
  },
  {
    "caption": "(A-E) Representative live cell microscopy images of D. discoideum infected with PflaA-GFP-producing L. pneumophila. D. discoideum Ax3 producing cytosolic mCherry (pDM1042) was infected (MOI 5) with (A, B) wild-type L. pneumophila JR32 (Ptac-mCherry-PflaA-gfp), (C, D) JR32 (Ptac-mCerulean-PflaA-gfp) or (E) ∆flaA (Ptac-mCerulean-PflaA-gfp) and embedded in agarose for 48 h. PflaA-GFP-positive L. pneumophila (A) escapes the LCV (0 sec), followed by other bacteria, which are contained in the cytosol and localize to the plasma membrane, where a PflaA-GFP-positive L. pneumophila first leaves the ruptured host cell (185 sec), or (B) triggers host cell death (loss of cytosolic mCherry) upon exit of the amoeba. PflaA-GFP-positive L. pneumophila (C) escape the LCV after 75 sec and spread within the cytosol for several minutes, and (D) are the first to exit the host cell, leading to the loss of cytosolic mCherry and host cell death. (E) L. pneumophila ∆flaA lyses the LCV and host cell less vigorously. Scale bars: 5 µm.",
    "ncbi_link": "flaA: 
GFP: 
gfp: 
mCerulean: 
mCherry: 
tac: "
  },
  {
    "caption": "(B) L. pneumophila bacteria lacking flaA or lqsA are impaired for spreading from amoebae. A. castellanii amoebae were infected (MOI 5, 52 h) with L. pneumophila JR32, ∆flaA or ∆lqsA harboring Ptac-mCherry-PflaA-gfp and embedded in 0.5% agarose/PYG medium. The fluorescence images are representative for the L. pneumophila strains indicated: JR32 (n = 25), ∆flaA (n = 13) or ∆lqsA (n = 19). Scale bars: 20 µm.",
    "ncbi_link": "flaA: 
lqsA: 
gfp: 
mCherry: 
tac: "
  },
  {
    "caption": "(A, B) Role of the Lqs system for PflaA expression in intracellular L. pneumophila. A. castellanii was infected (MOI 5, 48 h) with L. pneumophila JR32, ∆lqsA, ∆lqsR, ∆lqsS, ∆lqsT, or ∆lqsS-∆lqsT harboring Ptac-mCherry-PflaA-gfp, and (A) fixed and analyzed by confocal microscopy (representative 3D reconstructions, scale bars: 10 µm), or (B) lysed, fixed and analyzed by flow cytometry.",
    "ncbi_link": "gfp: 
lqsA: 
lqsT: 
mCherry: 
flaA: 
lqsR: 
lqsS: 
tac: "
  },
  {
    "caption": "(C-F) Role of the Lqs system for LCV escape and cytosolic localization of L. pneumophila. (C, D) A. castellanii or (E, F) D. discoideum was infected (MOI 5, 48 h) with L. pneumophila JR32, ∆lqsA, ∆lqsR, ∆lqsS, ∆lqsT, or ∆lqsS-∆lqsT harboring Ptac-mCherry-PflaA-gfp, fixed and treated with an anti‐ubiquitin antibody. Amoebae containing bacteria decorated with ubiquitin were quantified by confocal microscopy. Representative images of (C) A. castellanii (scale bars: 10 µm) or (E) D. discoideum (scale bars: 5 μm) infected with L. pneumophila JR32 escaping or not from the LCV are shown. The percentage of amoebae containing ubiquitinated bacteria was quantified by counting the total number of infected cells and the number of ubiquitinated cells: (D) JR32: n = 482; ΔlqsA: n = 834; ΔlqsR: n = 572; ΔlqsS: n = 729; ΔlqsT: n = 1469; ΔlqsS-ΔlqsT: n = 693; (F): JR32: n = 136; ΔlqsA: n = 201; ΔlqsR: n = 303; ΔlqsS: n = 183; ΔlqsT: n = 534; ΔlqsS-ΔlqsT: n = 180.",
    "ncbi_link": "gfp: 
lqsA: 
lqsR: 
lqsS: 
lqsT: 
mCherry: 
flaA: 
tac: "
  },
  {
    "caption": "(G, H) D. discoideum producing the LCV/PtdIns(4)P probe P4C-GFP and cytosolic-mCherry was infected (MOI 5, 48 h) with L. pneumophila JR32, ∆lqsA, ∆lqsR, ∆lqsS, ∆lqsT, ∆lqsS-∆lqsT, or ∆flaA harboring Ptac-mCerulean. Representative images of (G) D. discoideum infected with L.-pneumophila JR32 in intact cells with intact LCV (18.5%), lysed cells and lysed LCVs (60.2%), intact cells with lysed LCVs (15.5%) and lysed cells with intact LCVS (5.8%) are shown (scale bars: 5 µm). (H) The percentage of amoebae with intact LCVs was quantified by counting the total number of infected cells and the number of cells with intact LCV membrane: JR32: n = 426; ΔlqsA: n = 468; ΔlqsR: n = 344; ΔlqsS: n = 325; ΔlqsT: n = 287; ΔlqsS-ΔlqsT: n = 289; ΔflaA: n = 248.",
    "ncbi_link": "flaA: 
lqsA: 
lqsR: 
lqsS: 
lqsT: 
mCerulean: 
tac: "
  },
  {
    "caption": "D. discoideum producing the LCV/PtdIns(4)P probe P4C-mCherry was infected (MOI 5, 48 h) with L. pneumophila wild-type strains (JR32, Corby), or phospholipase triple mutants (∆plcABC, ∆plaACD) harboring the Ptac-mCerulean-PflaA-gfp reporter construct, and fixed and treated with an anti‐ubiquitin antibody, LCV escape and cytosolic localization of the bacteria was assessed by confocal microscopy through quantification of amoeba containing intact, P4C-mCherry-positive LCVs or ubiquitin-decorated, cytosolic bacteria. (A) Representative images of amoebae harboring L. pneumophila confined within LCVs or released from the LCV to the cytosol are shown (scale bars: 5 μm).",
    "ncbi_link": "gfp: 
mCerulean: 
flaA: 
plaA: 
plcA: 
tac: "
  },
  {
    "caption": "(A) Raw 264.7 cells were pre-treated with DMSO or the EGFR inhibitor gefitinib (10 µM) before cGAMP transfection; after 5h, IFNβ mRNA was measured by qRT-PCR (n=3).",
    "ncbi_link": "IFNβ: 15977"
  },
  {
    "caption": "(B) WT and EGFR knockdown Raw 264.7 cells were transfected with cGAMP; 4.5h post treatment, IFNβ mRNA was measured (n=3).",
    "ncbi_link": "EGFR: 13649
IFNβ: 15977"
  },
  {
    "caption": "(C) WT and EGFR-/- BMDMs were transfected with cGAMP; 5h post transfection, IFNα mRNA induction was measured (n=4).",
    "ncbi_link": "EGFR: 13649
IFNα: 111654"
  },
  {
    "caption": "(D) WT and EGFR-/- HeLa cells were transfected with cGAMP; after 5h IFNβ mRNA was measured (n=3).",
    "ncbi_link": "EGFR: 1956
IFNβ: 3456"
  },
  {
    "caption": "(H) MEF cells were pretreated with gefitinib for 1h and followed with cGAMP or Poly (I:C) transfection; 4.5h post treatment, total RNA was harvested and IFNα mRNA induction was measured (n=3).",
    "ncbi_link": "IFNα: 111654"
  },
  {
    "caption": "(A) MEF cells were pre-treated with gefitinib or DMSO for 1 hour, and then infected with HSV1 at m.o.i. of 1. 4 hours post infection (h.p.i.), IFNβ mRNA induction was monitored by qRT-PCR (n=3). Uninfected cells were used as negative control (U).",
    "ncbi_link": "IFNβ: 15977"
  },
  {
    "caption": "(C) WT and EGFR KO HeLa cells were infected with HSV1, RNA was extracted at 4 h.p.i. and IFNα mRNA induction was measured (n=3).",
    "ncbi_link": "EGFR: 1956
IFNα: 3439"
  },
  {
    "caption": "(E) Survival of WT and EGFRfl+/-LysMCre+/+ mice infected with HSV1.",
    "ncbi_link": "Cre: 2777477
EGFR: 13649
LysM: 17105"
  },
  {
    "caption": "WT and EGFRfl+/-LysMCre+/+ mice infected with HSV1. HSV1 titers in the brains of the live mice at day 9 were determined.",
    "ncbi_link": "Cre: 2777477
EGFR: 13649
LysM: 17105"
  },
  {
    "caption": "(E) STING-IRF3 interaction in human cells required EGFR: WT and EGFR-/- (KO) HeLa cells were transfected with cGAMP, 2h later cells were lysed, immunoprecipitated with anti-STING antibody and analyzed by Western blot.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(F) STING and IRF3 co-localized in the endosomes of stimulated cells: STING-/- MEF cells were transfected with STING-HA for 24 hours then treated with cGAMP for 1h. The cells were then stained with the HA (purple), CD63 (red) and IRF3 (green) antibodies. Imaging data were analyzed by the Fuji software to reveal co-localization as white dots. Scale bars represent 10 µ m.",
    "ncbi_link": "HA: 
STING: 72512"
  },
  {
    "caption": "(G) EGFR was not required for ligand-induced phosphorylation of STING Ser366: EGFR-/- HeLa cells or gefitinib-treated and untreated WT HeLa cells were treated with cGAMP for the indicated time and cell lysates were analyzed by Western blot.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(H) Kinetics of STING and IRF3 co-localization in the endosomes of stimulated cells: STING-/- MEF cells were transfected with STING-HA for 24 hours and treated with cGAMP for the indicated time. The cells were then stained with the HA (purple), CD63 (red) and IRF3 (green) antibodies and DAPI. Imaging data were analyzed by the Fuji software to reveal co-localization as white dots. Scale bars represent 10 µ m.",
    "ncbi_link": "HA: 
STING: 72512"
  },
  {
    "caption": "(C) STING Tyr-phosphorylation required EGFR. Raw 264.7 cells expressing EGFR shRNA (KD) or non-target shRNA (CO) were transfected with cGAMP for 2 hours; cell lysates were analyzed by Western blot before or after immunoprecipitation with anti-pTyr antibodies.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "(E) STING co-localized with EGFR after cGAMP stimulation. STING-/- MEF cells were transfected with STING-GFP (Green) for 24hours and stimulated with cGAMP for 1h, cells were fixed and labeled with EGFR (Red) and Calnexin (Purple) antibodies. Co-localization was analyzed by Fuji and co-localized dots are shown in white. Scale bars represent 10 µ m.",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": "(H) Poly I:C did not activate EGFR. STING-/- MEF cells were transfected with cGAMP or Poly (I:C); after 3h, p-EGFR were detected by Western blot.",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": "(A) In the absence of EGFR, after cGAMP stimulation, STING translocated out of the ER. STING-/- MEF cells were transfected with STING-GFP (Green) for 24h, pretreated with gefitinib 1h and transfected with cGAMP for 2.5h; cells were fixed and labeled with Calreticulin (ER marker, Red) antibody. Co-localization (Col) is indicated by white dots.",
    "ncbi_link": "STING: 72512"
  },
  {
    "caption": "STING-/- MEF cells were transfected with STING-GFP (Green) for 24h, pretreated with gefitinib 1h and transfected with cGAMP for 2.5h Co-localization (Col) is indicated by white dots. (B) STING was present in the ERGIC of stimulated cells in the presence or the absence of gefitinib. , the cells were labeled with P58 (ERGIC marker, Red) antibody.",
    "ncbi_link": "GFP: 
STING: 72512
STING: 340061"
  },
  {
    "caption": "MEF cells were transfected with STING-GFP (Green) for 24h, pretreated with gefitinib 1h and transfected with cGAMP for 2.5h Co-localization (Col) is indicated by white dots. (C) STING translocated to the autophagosomes in the absence of EGFR. the cells were labeled with LC3 (Autophagosome marker, Red) antibody. (E) In gefitinib-treated cells, STING was detected in the autophagosomes as early as 0.5h. The procedures were as in C.",
    "ncbi_link": "GFP: 
STING: 340061"
  },
  {
    "caption": "(F) STING translocation to late endosomes required EGFR activity. STING-/- MEF cells were transfected with STING-GFP (Green) for 24hours, pretreated with gefitinib for 1h and transfected with cGAMP for the indicated time periods; cells were fixed and labeled with CD63 (late endosome marker, Red) antibody.",
    "ncbi_link": "GFP: 
STING: 72512
STING: 340061"
  },
  {
    "caption": "products were analyzed on phos-tag gel by Western blot using GFP antibody (upper panel). The substrate was analyzed, before the assay incubations, by the same method (lower panel). (B) Y245F STING mutant is not a substrate of EGFR. WT and the indicated mutants of STING-GFP were purified and used as substrates for EGFR",
    "ncbi_link": "EGFR: 1956
STING: 340061"
  },
  {
    "caption": "(F) EGFR is required for STING Tyr phosphorylation. STING-GFP was expressed in 293XL cells in which EGFR expression had been knocked down. STING phosphorylation was analyzed by LC-MS/MS",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(G) Y245F STING mutant cannot trigger IFNβ mRNA induction. RNA was isolated from cells, expressing WT or Y245F STING, 3h after stimulation and subjected to qRT-PCR analysis (n=3).",
    "ncbi_link": "IFNβ: 3456
STING: 340061"
  },
  {
    "caption": "(H) Y245F STING is phosphorylated on S366 after stimulation of cells. Phosphorylation of S366 was detected in cells expressing the WT or the mutant STING after stimulation for the indicated time.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(I) TBK1, but not IRF3, can bind to Y245F STING and be phosphorylated in cGAMP-stimulated cells. Lysates from cells expressing the WT or the mutant STING were analyzed by Western blot after (upper panel) or before (lower panel) GFP pull down.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(J) Y245F mutant induced more LC3 lipidation after 1h cGAMP treatment of 293XL cells expressing WT or mutant STING.",
    "ncbi_link": "STING: 340061"
  },
  {
    "caption": "(A) STING-/- MEF cells were transfected with mSTING WT-GFP and Y244F-GFP (Green) for 24h, pretreated with gefitinib for 1h and transfected with cGAMP for the indicated time; cells were fixed and labeled with LC3 (autophagosome marker, Red) antibody. Co-localization (Col) is indicated by white dots.",
    "ncbi_link": "GFP: 
STING: 72512"
  },
  {
    "caption": "(A) STING-/- MEF cells were transfected with mSTING WT-GFP and Y244F-GFP (Green) for 24h, pretreated with gefitinib for 1h and transfected with cGAMP for the indicated time; cells were fixed and labeled with CD63 (late endosome marker).",
    "ncbi_link": "GFP: 
STING: 72512"
  },
  {
    "caption": "M ChIP assays with antibodies against CDK9 and Pho-Pol II were performed in siNC and siCHAF1A J-Lat 10.6 cells. ChIP signals in each group were normalized to Input.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "siRNAs targeting each CAF-1 subunits and corresponding enriched genes were transfected into TZM-bl cell lines respectively. The fold change of luciferase expression of each groups was normalized to siNC.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "F Upper panel showed WT-CHAF1A bodies. Lower panel showed dLLPS-CHAF1A which was CHAF1A-Q34A-I116A-K395D-R402D-K409D.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "B First panel: the co-localization of PCNA and CHAF1A. Second panel: the distribution of PCNA in the absence of endogenous CHAF1A. Third panel: the distribution of PCNA in the presence of CHAF1A-dPIP1 mutant and the absence of endogenous CHAF1A. Fourth panel: the co-localization of PCNA and over-expressed DNMT1 in the absence of endogenous CHAF1A.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "C Upper two panels: the distribution of HP1α in the presence or absence of CHAF1A. Lower two panels: the distribution of HP1α in the presence of CHAF1A-dHP1BD or CHAF1A-DS2-dHP1BD. Both images of lower two panels were in the absence of endogenous CHAF1A.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "The distribution of SUV39H2 (E) and MBD1 (F) in the presence or absence of CHAF1A.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "G The distribution of SUMO paralogs in the absence of CHAF1A.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "A Flow cytometry figures of CAF-1 body rescue experiment. First figure: Wildtype J-Lat 10.6. Second figure: CHAF1A knock-out J-Lat 10.6. Third figure: CHAF1A-KO J-Lat 10.6 was re-introduced with wildtype CHAF1A. Fourth figure: CHAF1A-KO J-Lat 10,6 was re-introduced with dLLPS-CHAF1A which harbored five mutations. The percentages of GFP-positive cells were labeled in the top right corner of each figure.",
    "ncbi_link": "CHAF1A: 10036"
  },
  {
    "caption": "D The amounts of intracellular HIV-1 RNAs of latently infected primary CD4+ T cells which were isolated from PBMCs of HIV-1-infected individuals. αCD3/αCD28/IL-2 treatment was performed as positive control. shCHAF1A lentiviruses were packaged to knock down endogenous CHAF1A. shluc lentiviruses treatment was performed as negative control. SAHA was added as LRA supplement.",
    "ncbi_link": "luc: 
CHAF1A: 10036"
  },
  {
    "caption": "(H)-(J) mRNA expression of (H) U2AF1, (I)  SMN2-FL, or (J) SMN2∆7 in SMA patient-derived fibroblasts  (red bars) 72 hours post-transfection with SMN2  SSO, scrambled siRNA, or U2AF1  siRNA at the indicated dose. Unaffected, SMA carrier fibroblasts  (blue bars) treated with scrambled siRNA. Data information: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; empirical p-values are determined by a simulation and sampling method The error bars show the Standard Error of Mean (SEM). Data represent 3 biological replicates. Three technical replicates were performed during qPCR  for each biological replicate and averaged. Scrambled siRNA condition for each experiment was set to 1.",
    "ncbi_link": "SMN2: 6607
U2AF1: 7307"
  },
  {
    "caption": "Western blots for phosphorylated ACC (S79) and STIM1 (S257 or S521) in L6 rat myoblasts with siRNA-mediated knockdown of endogenous STIM1 (siSTIM1) or transfected with scramble control siRNA (Control). Cells were treated with the AMPK activator A-769662 (+) or vehicle (-) for 30 min. Total STIM1 was used to demonstrate STIM1 knockdown efficiency. Total ACC and 14-3-3 were used as loading controls.",
    "ncbi_link": "STIM1: 361618"
  },
  {
    "caption": "Western blots for phosphorylated ACC (S79) and STIM1 (S257 or S521) in wild type (WT) or AMPK β1/β2 knockout (AMPKβ KO) mouse endothelial fibroblasts were isolated and treated with A-769662 (+) or vehicle (-) for 30 min. AMPKβ was used to demonstrate knockout, and AMPKɑ was used to demonstrate specificity for AMPKβ. Total ACC and STIM1 were used as loading controls.",
    "ncbi_link": "AMPK β1: 19079
β2: 108097
AMPKβ: 108097///19079"
  },
  {
    "caption": "Western blots for phosphorylated ACC (S79) and STIM1 (S257 or S521) in wild type (WT) or AMPK KO mouse endothelial fibroblasts were isolated and treated with 2 µM thapsigargin (+) or vehicle (-) for 15 min.",
    "ncbi_link": "AMPK: 108097///19079"
  },
  {
    "caption": "L6 myoblasts were transfected with the genetic cytosolic Ca2+ sensor GCaMP6s. Cells were also transfected with non-targeted siRNA (Control) or siRNA directed at endogenous STIM1 (siSTIM1). Some cells with endogenous STIM1 knockdown were also transfected with full-length wild type (WT) or mutant (S257A, S257E or L251S) STIM1-mRuby3. Representative microscopy images of GCaMP6s signal indicating SOCE in L6 myoblasts,",
    "ncbi_link": "GCaMP6s: 
mRuby3: 
STIM1: 361618
STIM1: 6786"
  },
  {
    "caption": "L6 myoblasts were transfected with the genetic cytosolic Ca2+ sensor GCaMP6s. Cells were also transfected with non-targeted siRNA (Control) or siRNA directed at endogenous STIM1 (siSTIM1). Some cells with endogenous STIM1 knockdown were also transfected with full-length wild type (WT) or mutant (S257A, S257E or L251S) STIM1-mRuby3. Ca2+ levels over time (fold of 0 mM Ca2+ + EGTA basal) and (C) quantification of SOCE in in L6 myoblasts incubated in buffer containing 1 or 0 mM Ca2+ and treated with 2 µM thapsigargin during the indicated times.",
    "ncbi_link": "GCaMP6s: 
mRuby3: 
STIM1: 361618"
  },
  {
    "caption": "Negative geotaxis climbing assays in Drosophila (flies). Time required for 50% of flies to climb to the target line before or after 2.5 hr of continuous climbing exercise (A) in the yw strain with muscle-specific STIM knockdown using two independent RNAi sequences (RNAi26-1 or RNAi8-4) compared to GFP-expressing controls, or (B) in the w1118 strain with muscle-specific STIM knockdown using RNAiGD16187 compared to non-targeted RNAiGD12145 controls.",
    "ncbi_link": "GFP: 
STIM: 32556"
  },
  {
    "caption": "Time to fatigue, when flies were no longer able to climb, during a 3-min period after negative geotaxis stimulation in STIM whole-body knockout flies overexpressing wild type (WT) or mutant (S257A or S257E) human STIM1-mRuby3.",
    "ncbi_link": "mRuby3: 
STIM: 32556
STIM1: 6786"
  },
  {
    "caption": "(B) IP of YFP-B56α from cells stably expressing the B56α WT, R222E, and 5A followed by immunoblotting of indicated proteins. Representative blots are shown (top). hSgo1 signals were normalized to YFP and plotted (bottom). Error bars represent SD (n=4).",
    "ncbi_link": "B56α: 5525"
  },
  {
    "caption": "(C) Reciprocal IP of (B). YFP-hSgo1 expression construct was transfected into cells stably expressing FLAG-B56α WT, R222E and 5A, followed by YFP IP and immunoblotting of indicated proteins. Representative blots are shown (top). B56α signals were normalized to YFP and plotted (bottom). Error bars represent SD (n=4).",
    "ncbi_link": "FLAG: 
YFP: 
B56α: 5525
Sgo1: 151648"
  },
  {
    "caption": "(F) hSgo1 RNAi and rescue with the indicated B56α variants fused to YFP and the Cenp B centromere-targeting domain (CB). Representative images of chromosome spreads are shown. CB targets all the rescue constructs (green) to the centromere. Scale bar, 5μm. (G) Quantification of (F). The distance between the two peak intensities of YFP was measured for 5 kinetochore pairs and averaged for a single cell and plotted. The data are from 3 independent experiments and the mean and SD are indicated.",
    "ncbi_link": "YFP: 
B56α: 5525
Sgo1: 151648"
  },
  {
    "caption": "(D) Localization of B56α in cells depleted of hSgo1 and expressing the indicated YFP-hSgo1 variants. Representative immunofluorescent images are shown. Scale bar, 5μm. (E) B56α signal intensity was quantified. B56α signal from each cell was determined from 5 kinetochore pairs and normalized to YFP-hSgo1 signal. Each circle represents an individual cell, and the average and SD are indicated.",
    "ncbi_link": "YFP: 
Sgo1: 151648"
  },
  {
    "caption": "(F) Mitotic U2OS LacO Haspin CM cells expressing hSgo1-LacI-GFP variants or LacI-GFP (control) were stained for PP2A-C. Scale bar, 5μm. (G) PP2A-C signal intensity was quantified, normalized to GFP, and then plotted. Each circle represents an individual cell, and the mean fluorescent intensity is indicated. Representative of at least 3 independent experiments.",
    "ncbi_link": "GFP: 
LacI: 
LacO: 
Haspin: 83903
Sgo1: 151648"
  },
  {
    "caption": "(A) Representative images of chromosome spreads from hSgo1 RNAi treated cells stably expressing the indicated YFP-hSgo1 variants. All the YFP-hSgo1 rescue constructs (green) localize to the centromeres (CREST, red). Scale bar, 5μm. (B) The distance between the two peak intensities of CREST was measured for 5 kinetochore pairs from the chromosome spreads in (A) and averaged for a single cell. The data are from 3 independent experiments and the mean and SD are indicated.",
    "ncbi_link": "YFP: 
Sgo1: 151648"
  },
  {
    "caption": "(C) IP of YFP-hSgo1 from cells stably expressing hSgo1 WT, 3A, and 4A followed by immunoblotting of cohesin components, Smc1 and Smc3. Representative blots are shown (top). Signals were quantification by LiCor, normalized to YFP and plotted (bottom). Error bars represent SD (n=4 for Smc1 and n=3 for Smc3).",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "(F) hSgo1 RNAi and rescue with the indicated hSgo1 RNAi-resistant constructs was performed. Representative still images captured during the live cell imaging showing DIC and YFP-hSgo1 WT, 3A, and 4A localization during mitosis. Time (min) from nuclear envelop breakdown (NEBD) is indicated. Scale bar, 15μm.",
    "ncbi_link": "Sgo1: 151648"
  },
  {
    "caption": "(c) qPCR gene expression scores of the 5-gene signature (∆∆CT over PPIA) for CTRLs, 03NP-sEF, 03NP-SPT and 03NP-ST samples from Nepal. Yellow diamonds in the 03NP-sEF category represent the 9 patients classified as EF based on the random forest algorithm.",
    "ncbi_link": "PPIA: 5478"
  },
  {
    "caption": "(d) qPCR expression values (∆∆Ct over PPIA) of the 5-gene signature in control samples (Oxford and Nepal), S. Paratyphi A (03NP-SPT) or S. Typhi (03NP-ST) in Nepal, samples at day 7 after challenge of participants who stayed well following challenge with S. Typhi (nD7), or typhoid diagnosis after challenge (TD) in the Vi-TCV study",
    "ncbi_link": "PPIA: 5478"
  },
  {
    "caption": "(f) Temperature and CRP for samples of which data was available (CRP was only measured in the Oxford CHIM). D0 = pre-challenge baseline Vi-TCV study; nD7 = day 7 samples of participants who stayed well following challenge (Vi-TCV study); SPT = S. Paratyphi A (03NP); ST = S. Typhi (03NP); TD = Typhoid diagnosis (Vi-TCV study). (g) Spearman's rank correlation of the 5-gene combined expression score and (left) temperature (only nD7 and TD samples from the Oxford CHIM - Vi-TCV and SPT and ST cases from Nepal at presentation to hospital were included) and (right) CRP (CRP was only available for Oxford CHIM - Vi-TCV samples and we excluded D0 baseline measures).",
    "ncbi_link": "CRP: 1401"
  },
  {
    "caption": "Representative immunoprecipitation (IP) of HEK293 cells transfected with indicated cDNAs. (A) CTGF interacts with LRP4 but not with MuSK. Full-length CTGF (CTGF-full-myc) was immunoprecipitated with the ectodomain of LRP4 (LRP4ect-Flag, lane 6) but not with the ectodomain of MuSK (MuSKect-Flag, lane 3). However, when CTGF-full-myc, LRP4ect, and MuSKect-Flag were expressed together, CTGF-full-myc was immunoprecipitated with MuSKect-Flag (lane 5). The CT domain of CTGF (CTGF-CT-myc) was sufficient to immunoprecipitate LRP4ect-Flag (lane 7). Predicted positions of full-length and shortened CTGF proteins are indicated by bars and/or asterisks.",
    "ncbi_link": "Flag: 
myc: 
CTGF: 1490
LRP4: 4038
MuSK: 18198"
  },
  {
    "caption": "Representative immunoprecipitation (IP) of HEK293 cells transfected with indicated cDNAs. (B) Deletion of the CT domain of human CTGF (CTGF-ΔCT_ΔTSP1 and CTGF-ΔCT) impairs the interaction between CTGF and LRP4ect-Flag. Predicted positions of full-length and shortened CTGF proteins are indicated by bars and/or asterisks.",
    "ncbi_link": "Flag: 
CTGF: 1490"
  },
  {
    "caption": "Representative immunoprecipitation (IP) of HEK293 cells transfected with indicated cDNAs. (C) Anti-CTGF antibody immunoprecipitated human LRP4 deleted with the 1st, 2nd, and 4th β-propeller domains (Δ1, Δ2, and Δ4) but not with the 3rd β-propeller domain (∆3).",
    "ncbi_link": "LRP4: 4038"
  },
  {
    "caption": "(C) Representative immunoblotting of Lrp4, MuSK, CTGF, and TfR in whole tissue lysates and the plasma membrane fraction of lower limb muscles at E18.5 of wild-type (WT) and Ctgf-/- mice.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(D) Representative immunoblotting of Y755-phosphorylated MuSK, total MuSK, and β-actin in the diaphragm at E18.5 of wild-type (WT), Ctgf-/-, and Ctgf+/- mice.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(C) C2C12 myotubes were infected with lentivirus expressing shControl, shCtgf-1, or shCtgf-2. Doxycycline was added for 2 days to induce shRNA expression. BSA or agrin was added to the medium at 10 pM. Total MuSK was immunoprecipitated (IP) by an anti-MuSK antibody, and phosphorylated MuSK was immunoblotted with an anti-phosphotyrosine (p-Tyr) antibody. Ctgf knockdown suppressed MuSK phosphorylation.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(D) Ten pM agrin was added to the medium. AChRs were visualized with Alexa594-conjugated α-bungarotoxin (red signals) in the infected myotube (green GFP signals). Ctgf knockdown decreased the number and length of AChR clusters. Scale bar = 10 µm.",
    "ncbi_link": "GFP: 
Ctgf: 14219"
  },
  {
    "caption": "(A) Quantitative RT-PCR of Chrne, Musk, Lrp4, and Ctgf in C2C12 myotubes treated with 10 ng/ml BSA or recombinant human CTGF.",
    "ncbi_link": "Ctgf: 14219
CTGF: 1490
Chrne: 11448
Lrp4: 228357
Musk: 18198"
  },
  {
    "caption": "(B) Quantitative RT-PCR of Ctgf in C2C12 myotubes treated with indicated combinations of 10 ng/ml agrin and/or 10 ng/ml neuregulin-1.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(C) Localizations of CTGF and AChR in a representative cross section of the lower limb muscle at E18.5. Co-localization of AChR (red) and CTGF (green) is indicated in the merged images. Red arrow points to an AChR cluster. Scale bar = 20 μm.",
    "ncbi_link": "CTGF: 14219"
  },
  {
    "caption": "(D) Quantitative RT-PCR of Ctgf and neural Agrn in the spinal cord and the diaphragm in mouse. Mean and SD (n = 3 mice) are indicated. p-value < 0.05 by two-way repeated measures ANOVA. p < 0.05 by post-hoc Tukey test is indicated by a single letter representing each group.",
    "ncbi_link": "Agrn: 11603
Ctgf: 14219"
  },
  {
    "caption": "(A) Representative confocal images of the left diaphragm at E18.5 labeled with α-bungarotoxin (red) and anti-peripherin antibody (green) to visualize AChRs and the motor axon, respectively. The endplates of Ctgf-/- diaphragm were smaller (lower left panel) than those of the wild-type diaphragm (upper left panel). In the Ctgf-/- diaphragm, 10.0 ± 3.2% (mean and SD, n = 105 in 5 embryos) of peripherin-positive axons passed through the AChR-positive areas. In contrast, in the wild-type diaphragm, 2.0 ± 1.4% (mean and SD, n = 102 in 5 embryos) of peripherin-positive axons passed through the AChR-positive areas. Quantification was performed in a blinded manner. Scale bar = 5 µm.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(B) Representative confocal images of the left diaphragm at E18.5 labeled with α-bungarotoxin (red) and anti-synaptophysin antibody (green) to visualize AChRs and the nerve terminal, respectively. Synaptophysin signals mostly overlapped with α-bungarotoxin signals in the wild-type diaphragm, whereas synaptophysin signals extended into the axon in the Ctgf-/- diaphragm. Scale bar = 5 µm.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(C-E) Blinded morphometric analysis of AChR signals (C), synaptophysin signals (D), and the ratio of synaptophysin signals not colocalized with AChR signals (E) of confocal images shown in (A) and (B). AChR areas (C), but not synaptophysin-positive areas (D), were decreased in Ctgf-/- mice at E18.5. (E) A large fraction of synaptophysin signalswere not colocalized with AChR signals in Ctgf-/- diaphragm. Mean and SD (n = 40-50 NMJs in 6 left diaphragms) are indicated. p-value < 0.05 by one-way ANOVA for (C and E), but not for (D). p < 0.05 by post-hoc Tukey test is indicated by a single letter representing each group.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "(F) Representative electron micrographs of the NMJs in the diaphragm of wild-type and Ctgf-/- mice at E18.5. In Ctgf-/- mice, synaptic vesicles are sparser and the number of mitochondria at the nerve terminals is reduced compared to those in wild-type mice. See Table 1 for morphometric analysis. Regions indicated by rectangles are enlarged in the insets. Arrowheads point to synaptic vesicles (SV). Mit, mitochondria. Blinded morphometric measurements are shown in Table 1. Scale bar = 500 nm.",
    "ncbi_link": "Ctgf: 14219"
  },
  {
    "caption": "Effect of HK2 targeting on in vitro tumorigenicity. HK2-silencing with two different shRNAs (shHK2-1 and shHK2-2) in CT26 colon cancer cells (A) Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control.",
    "ncbi_link": "HK2: 15277"
  },
  {
    "caption": "Effect of HK2 targeting on in vitro tumorigenicity. HK2-silencing with two different shRNAs (shHK2-1 and shHK2-2) in CT26 colon cancer cells inhibits growth in soft agar (B; colony area±SEM; n=6 replicates obtained from 3 independent experiments; Student's t test ***p<0.001; A.U., arbitrary units). Data information: Throughout the Figure, cl-SCRpep or SCRpep are used as peptide negative control.",
    "ncbi_link": "HK2: 15277"
  },
  {
    "caption": "A GS∆44 myoblasts were transfected with an empty vector (CTRL) or with a CELF2a overexpressing construct (OE CELF2A) (Martone et al, 2016). Cells were collected after 10 days in differentiation medium (DM) and the RNA was analysed by RT-PCR for CELF2a expression and DMD exon 45 skipping. GAPDH was used as loading control. The arrow indicates the DMD exon 45 skipped band. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
CELF2A: 10659
DMD: 1756"
  },
  {
    "caption": "B Representative immunofluorescence for Myosin Heavy Chain (MHC in red) in combination with DAPI staining (in blue) of iPSCs obtained from WT (WT#1), UP∆44 (UP∆44#3) and ∆44 edited clones (UP∆44#3.1 and UP∆44#3.5) differentiated for 9 days into myocytes by MYOD/BAF60c overexpression. Scale bar 100 μm.",
    "ncbi_link": "MYOD: 17240
BAF60c: 6604"
  },
  {
    "caption": "D RNA extracted from myocytes obtained by differentiation of WT (WT#1), UP∆44 (UP∆44#3) and edited UP∆44 iPSC (UP∆44#3.1 ∆CELF2a and UP∆44#3.5 ∆CELF2a) clones was analysed by RT-PCR for CELF2a, CELF2b, CELF2c and DMD exon 45 skipping. GAPDH was used as loading control. The arrow indicates the DMD exon 45 skipped band. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
CELF2b: 10659
CELF2c: 10659
DMD: 1756"
  },
  {
    "caption": "E Western blot on proteins (40 μg) extracted from myocytes obtained by differentiation of WT (WT#1), UP∆44 (UP∆44#3) and edited UP∆44 iPSC (UP∆44#3.1 ∆CELF2a and UP∆44#3.5 ∆CELF2a) clones probed with antibodies against dystrophin (DMD). Actinin (ACTN) was used as a loading control. For the WT 5% sample 2 μg of proteins were diluted in 38 μg of proteins belonging to UP∆44#3 to reach a total amount of 40 μg. Representative results are shown (n=3).",
    "ncbi_link": "CELF2a: 10659"
  },
  {
    "caption": "A iPSCs obtained from a control (WT#1; (Lenzi et al, 2015), GS∆44 (GS∆44#2, GS∆44#8) and GSM (GSM#1) were differentiated into myocytes by MYOD/BAF60c overexpression. Cells were collected before the induction (iPSC) and after 9 days in DM (Myo) and RNA was analysed by RT-PCR for CELF2a, CELF2b, CELF2c and DMD expression. GAPDH was used as loading control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
CELF2b: 10659
CELF2c: 10659
DMD: 1756
MYOD: 17240
BAF60c: 6604"
  },
  {
    "caption": "B Representative immunofluorescence for Myosin Heavy Chain (MHC in red) in combination with DAPI staining (in blue) of iPSCs obtained from WT#1, GS∆44 (GS∆44#8) and GS∆44 edited clones (GS∆44#8.2) differentiated for 9 days into myocytes by MYOD/BAF60c overexpression. Scale bar 100 μm. C Histogram represents fusion index quantification. At least 7 randomly chosen microscope fields of two independent biological samples were analysed (n=2). Data are presented as mean ± SD of the biological replicates.",
    "ncbi_link": "MYOD: 17240
BAF60c: 6604"
  },
  {
    "caption": "D RNA extracted from myocytes obtained by differentiation of WT#1, GS∆44 (GS∆44#8) and GS∆44 edited clones (GS∆44#8.2 ∆CELF2a) was analysed by RT-PCR for CELF2a, CELF2b, CELF2c and DMD exon 45 skipping. GAPDH was used as loading control. The arrow indicates the DMD exon 45 skipped band. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
CELF2b: 10659
CELF2c: 10659
DMD: 1756"
  },
  {
    "caption": "E Western blot on proteins (40 μg) extracted from myocytes obtained by differentiation of WT (WT#1), GS∆44 (GS∆44#8) and edited GS∆44 (GS∆44#8.2 ∆CELF2a) iPSC clones probed with antibodies against dystrophin (DMD). Actinin (ACTN) was used as a loading control. For the WT 5% sample, 2 μg of proteins were diluted in 38 μg of proteins belonging from GS∆44#8 to reach the total amount of 40 μg. Representative results are shown (n=3).",
    "ncbi_link": "CELF2a: 10659"
  },
  {
    "caption": "A DNA accessibility (ATAC-sequencing) and chromatin marks (ChIP-seq) signals in the Celf2 region (+/- 50kb) using the UCSC genome browser. ATAC-seq peaks called in the two conditions are reported below each track. The differential peaks specific for one of the two conditions are reported in the tracks ATACseq_specific peaks_WT and ATACseq_specific peaks_GS∆44. ChIP-seq signals for H3K4me3, H3K27ac and H3K27me3 in WT and GSΔ44 myoblasts (WT myoblasts in light orange; GSΔ44 myoblasts in light blue). ChIP-seq for MyoD in control cells was obtained from (MacQuarrie et al, 2013) (GSM1218849). Orange boxes highlight the regions containing the first exon of each isoform (a, b and c).",
    "ncbi_link": "Celf2: 10659"
  },
  {
    "caption": "D Chromatins extracted from Control (WT) and GS∆44 myoblasts were immunoprecipitated with anti-MyoD and control IgG antibodies. Regions corresponding to the MyoD binding sites present in Peak A (see Figure EV3D) and in the MAFA and LSTZ2 genes were analysed by qPCR. Fold enrichments of PeakA over MAFA or LSTZ2 immunoprecipitation (IP) are plotted for WT and GS∆44 samples. The mean ± SEM of triplicates from one representative among three experiment is shown. Statistical significance of differences between means was assessed by a two-tailed t-test and P<0.05 was considered significant. *P=0.0339, **P=0.0067.",
    "ncbi_link": "LSTZ2: 84445
MAFA: 389692"
  },
  {
    "caption": "B RT-PCR analyses of indicated RNAs in control (WT), ∆44 and in GS∆44 myocytes collected after 9 days upon the induction of differentiation. GAPDH was used as control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "C RT-PCR analyses for CELF2a and DUXAP8 expression in WT and GS∆44 myoblasts (GM) and myocytes (DM). GAPDH was used as control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
DUXAP8: 503637"
  },
  {
    "caption": "D RT-PCR analysis of DUXAP8 expression in RNA extracted from GS∆44, GS∆44's mother (GSM) and GS∆44's father (F) fibroblasts. GAPDH was used as control. Lane (-) indicates the negative control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
DUXAP8: 503637"
  },
  {
    "caption": "E RT-PCR analysis for DUXAP8 expression in RNA extracted from WT and GS∆44 myocytes and from WT (WT#1), GS∆44 (GS∆44#2, GS∆44#8) and GSM (GSM#1) iPSCs induced to differentiation for 9 days. GAPDH was used as control. Lane (-) indicates the negative control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
DUXAP8: 503637"
  },
  {
    "caption": "F RT-PCR for the indicated RNAs on extracts from GS∆44 myoblasts treated with either control siRNAs (siSCR) or siRNAs against DUXAP8 (siDUXAP8) and collected two days after transfection. GAPDH was used as control. Lane (-) indicates the negative control. Representative results are shown (n=3).",
    "ncbi_link": "GAPDH: 
DUXAP8: 503637"
  },
  {
    "caption": "G qPCR analysis of DUXAP8 and CELF2a expression in control myoblasts transfected with a plasmid for the overexpression of DUXAP8 (OE DUXAP8) or an empty vector (Empty), and collected after 96h. Relative mRNA levels were calculated with the delta delta Ct method. qPCR reactions were normalized against an internal control (GAPDH) and plotted relative to the expression level in the sample treated with the empty vector which was set to a value of 1. The mean ± SEM of triplicates from one representative experiment is shown (n=3).",
    "ncbi_link": "GAPDH: 
CELF2a: 10659
DUXAP8: 503637"
  },
  {
    "caption": "(c) HA-Ulk1 was transfected into HEK293 cells together with wild-type (WT) AMPKα1 or a kinase-dead (DN) mutant. Cells were starved of glucose (4 h; Glu) or amino acids (-A.A) and treated with compound C (20 μM, C.C) as indicated. Ulk1 mobility as well as phosphorylation levels of ACC and S6K were determined by western blotting.",
    "ncbi_link": "AMPKα1: 5562
Ulk1: 8408"
  },
  {
    "caption": "(f) AMPK wild-type (WT) and α1/α2 double knockout (DKO) MEFs were incubated with or without glucose (4 h). Endogenous Ulk1 was immunoprecipitated and autophosphorylation was measured (mean ± s.d., n = 3). Autophosphorylation activity was normalized to Ulk1 protein level; relative activity is calculated by normalization to Ulk1 activity from AMPK wild-type MEFs in glucose-rich conditions.",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "(g) HA-Ulk1 was transfected into HEK293 cells together with vector (Vec) or an AMPKα1 kinase-dead mutant (DN). The cells were starved of glucose (-Glu) or amino acids (-A.A), or treated with 50 nM rapamycin (Rapa) for 3 h before lysis. Left: autophosphorylation activity was assessed and normalized as in f (mean ± s.d., n = 3). Right: fold induction in Ulk1 autophosphorylation, compared with Ulk1 autophosphorylation from cells under nutrient-rich conditions. Uncropped images of blots are shown in Supplementary Fig. S5.",
    "ncbi_link": "AMPKα1: 5562
Ulk1: 8408"
  },
  {
    "caption": "(a) AMPK phosphorylates the Ulk1 S/T domain in vitro. Top: schematic representation of Ulk1 domain structure and deletion constructs used to map phosphorylation sites. The mouse Ulk1 protein consists of an N-terminal kinase domain (KD; 1-278), serine/threonine-rich domain (S/T domain, 279-828), and C-terminal domain (CTD, 829-1051). Bottom: the indicated Flag-Ulk1 deletion mutants were immunopurified from transfected HEK293 cells and were used for in vitro AMPK assay as a substrate. Phosphorylation was examined by 32P-autoradiogram and protein level was determined by western blot.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(b) Determination of AMPK phosphorylation sites in Ulk1. The indicated recombinant GST-Ulk1 mutants were expressed and purified from Escherichia coli, and used as substrates for in vitro phosphorylation by AMPK. Deletion analyses indicated that two Ulk1 fragments in the S/T domain, 279-425 and 769-782, were highly phosphorylated by AMPK in vitro. Mutation of Ser 317 abolished the majority of phosphorylation in the Ulk1 fragment 279-425. Within the fragment 769-782, mutations of five serine residues (Ser 774, Ser 777, Ser 778, Ser 779 and Ser 780) to alanine, denoted as (769-782) 5SA, completely abolished the phosphorylation by AMPK. Reconstitution of Ser 777 in this mutation background, (769-782) 4SA-S777, but not any of the other four residues, restored the phosphorylation by AMPK. GST and GST-TSC2F (TSC2 fragment 1300-1367 containing AMPK phosphorylation site at Ser 1345) were used as negative and positive controls for AMPK reaction, respectively. Phosphorylation was determined by 32P-autoradiograph and the protein levels were detected by Coomassie staining.",
    "ncbi_link": "TSC2: 7249
Ulk1: 8408"
  },
  {
    "caption": "(c) Ser 317/Ser 777 are required for glucose-starvation induced Ulk1 phosphorylation in vivo. HA-Ulk1 and mutants were transfected into HEK293 cells. Cells were starved for glucose for 4 h as indicated. HA-Ulk1 was immunoprecipitated and examined by western blot for mobility.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(d) Phosphorylation of Ulk1 Ser 317 and Ser 777 are induced by AMPK. Wild-type HA-Ulk1 or S317/777A mutant were co-transfected with AMPK into HEK293 cells as indicated. HA-Ulk1 was immunoprecipitated (IP) and phosphorylation of Ser 317 and Ser 777 were determined by western blotting. Uncropped images of blots are shown in Supplementary Fig. S5.",
    "ncbi_link": "AMPK: 5571///5563///5564///5562
Ulk1: 8408"
  },
  {
    "caption": "(a) AMPK wild-type or DKO MEFs were starved of glucose (4 h) as indicated. Total cell lysates were probed for Ulk1 protein and phosphorylation.",
    "ncbi_link": "AMPK: 108079///105787"
  },
  {
    "caption": "(e) The indicated HA-Ulk1 proteins were immunopurified from transfected HEK293 cells grown in high-glucose medium, and then incubated with AMPK in the presence of cold ATP for 15 minin vitro. After the reaction, AMPK was removed by extensive washing, the resulting Ulk1 immuno-complexes were assayed for kinase activity in the presence of 32P-ATP.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(f) HA-Ulk1 proteins (wild type or S317/777A mutant) were immunoprecipitated from the transfected HEK293 cells, which were incubated with or without glucose (4 h) before lysis. An in vitro kinase reaction was performed in the presence of GST-ATG13 and FIP200. Uncropped images of blots are shown in Supplementary Fig. S5.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(a) AMPK interacts with Ulk1. HEK293 cells were transfected with the various Flag-Ulk1 deletion mutants together with AMPK α/β/γ, Atg13 and FIP200. Flag-Ulk1 protein (indicated by white arrows) was immunoprecipitated and co-immunoprecipitation of AMPK α/β/γ, Atg13 and FIP200 were examined by western blots.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(b) Deletion analysis of Ulk1 regions responsible for AMPK interaction. The indicated Flag-Ulk1 truncation mutants were immunoprecipitated from transfected HEK293 cells co-expressing AMPK complex (α/β/γ). Co-immunoprecipitation of AMPK subunits was determined by western blots.",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(c) Rheb inhibits the Ulk1-AMPK interaction. HA-AMPKα, Flag-Ulk1 and Myc-Rheb were co-transfected into HEK293 cells as indicated. Cells were treated with or without rapamycin (50 nM Rapa) for 1 h before lysis. Flag-Ulk1 was immunoprecipitated and co-immunoprecipitates of AMPKα were determined by western blot.",
    "ncbi_link": "Rheb: 6009
Ulk1: 8408"
  },
  {
    "caption": "(d) Rapamycin treatment enhances the interaction of endogenous Ulk1 and AMPK. Endogenous Ulk1 proteins were immunoprecipitated from either Ulk1 or AMPK wild-type and knockout (single-knockout; KO or double-knockout; DKO) MEFs. Treatment with 50 nM rapamycin for 1 h is indicated (Rapa). Co-immunoprecipitation of endogenous AMPKα protein was determined by western blot. The arrow indicates AMPKα protein.",
    "ncbi_link": "AMPK: 108079///105787
Ulk1: 8408"
  },
  {
    "caption": "(a) mTORC1 phosphorylates the Ulk1 S/T domain. Ulk1 deletion mutants were prepared from the transfected HEK293 cells and used for in vitro mTORC1 assay. Phosphorylation was examined by 32P-autoradiogram (top) and protein level was determined by western blot (bottom).",
    "ncbi_link": "Ulk1: 8408"
  },
  {
    "caption": "(b) Ser 757 is phosphorylated by mTORC1. Left: the indicated recombinant GST-mUlk1 mutants were purified from E. coli and used for in vitro mTORC1 assay as substrates. Deletion analyses isolated the fragment (753-771) as a target for mTORC1. The Ulk1 (753-771) fragment contains five conserved serine/threonine residues, Thr 754, Ser 757, Ser 760, Thr 763 and Thr 770. Right: mutation of Ser 757 abolished Ulk1 phosphorylation by mTORC1 in vitro. GST was used as negative control for mTORC1 phosphorylation reaction. Phosphorylation was determined by 32P-autoradiograph (top), whereas protein levels were detected by Coomassie staining (bottom).",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(c) Rheb increases Ulk1 Ser 757 phosphorylation. HA-Ulk1 wild type and the S757A mutant were immunoprecipitated from transfected HEK293 cells. Co-transfection with Rheb and rapamycin (Rapa) treatment are indicated. Ulk1 Ser 757 phosphorylation was determined by western blot.",
    "ncbi_link": "Rheb: 6009
Ulk1: 8408"
  },
  {
    "caption": "(d) Rheb induces a mobility shift in wild-type Ulk1, but not the Ulk1S757A mutant. HA-Ulk1 was transfected with or without Rheb into HEK293 cells. HA-Ulk1 was immunoprecipitated from the cells under nutrient-rich medium and Ulk1 mobility was examined by western blot.",
    "ncbi_link": "Rheb: 6009
Ulk1: 8408"
  },
  {
    "caption": "(e) Endogenous Ulk1 Ser 757 phosphorylation is elevated in Tsc1−/− Tsc1. Tsc1+/+ (WT) and Tsc1−/− (KO) MEFs were starved of glucose (4 h), or treated with 50 nM rapamycin (Rapa, 1 h). Ser 757 phosphorylation of endogenous Ulk1 was detected by a phospho-Ulk1 Ser 757 antibody. Uncropped images of blots are shown in Supplementary Fig. S5.",
    "ncbi_link": "Tsc1: 64930"
  },
  {
    "caption": "(a) Ulk1 Ser 757 is required for mTORC1 to regulate the interaction of Ulk1 with AMPK in vivo. CBP/SBP tagged Ulk1 (wild type or S757C) was co-transfected with HA-AMPKα and Rheb into HEK293 cells as indicated. Ulk1 was purified by streptavidin beads and the co-precipitatedHA- AMPKα was examined by western blot (Rapa, 50 nM rapamycin treatment for 1 h before cell lysis).",
    "ncbi_link": "Rheb: 6009
Ulk1: 8408"
  },
  {
    "caption": "(b) Ulk1 Ser 757 is required for rapamycin to enhance the Ulk1-AMPK interaction in vitro. CBP/SBP Ulk1 proteins (wild type or S757C) were prepared from transfected HEK293 cells, which were pre-incubated with 50 nM rapamycin (Rapa, 1h) as indicated. The Ulk1 proteins were purified by streptavidin beads and the resulting Ulk1-bead was incubated with the bacterial purified AMPKα/β/γ complex. AMPKα protein levels in the in vitro pulldown assays were examined by western blot using AMPKα antibody. L.E.; long exposure.",
    "ncbi_link": "AMPK: 5571///5563///5564///5562
Ulk1: 8408"
  },
  {
    "caption": "(c) Phosphorylation of AMPK sites Ser 317 and Ser 777 in Ulk1 are decreased in Tsc1−/− Tsc1. Tsc1+/+ (WT) and Tsc1−/− (KO) MEFs were starved of glucose (4 h), or treated with 50 nM rapamycin (Rapa, 1 h). Ser 317 and Ser 777 phosphorylation of endogenous Ulk1 was examined by western blotting with antibodies against Ulk1 phosphorylated at Ser 317 or Ser 777.",
    "ncbi_link": "Tsc1: 64930"
  },
  {
    "caption": "(d) Rheb suppresses Ulk1 Ser 317 and Ser 777 phosphorylation in a manner dependent on mTORC1. HA-Ulk1, AMPKα kinase-dead mutant (DN), and Myc-Rheb were co-transfected into HEK293 cells as indicated. The cells were incubated with glucose-free medium (-Glu, glucose), in which either 20 μM compound C (C.C.) or 50 nM Rapamycin (Rapa) was added. Total cell lysates were probed with antibodies against Ulk1 phosphorylated at Ser 317, Ser 777, Ser 757, and HA, as indicated.",
    "ncbi_link": "AMPKα: 5560///5563
Rheb: 6009"
  },
  {
    "caption": "(e) Rheb inhibits glucose starvation-induced Ulk1 activation. HA-Ulk1 and Myc-Rheb was transfected into HEK293 cells, which were incubated with glucose-free (-Glu), amino-acid-free (-A.A) medium, or 50 nM rapamycin (Rapa) for 4 h before lysis. HA-Ulk1 was immunoprecipitated and kinase assays were performed. Ulk1 activity was measured by 32P-autoradiogram and the protein level of HA-Ulk1 and GST-Atg13 used in the assay was determined by western blot and by Coomassie staining, respectively. Uncropped images of blots are shown in Supplementary Fig. S5.",
    "ncbi_link": "Rheb: 6009"
  },
  {
    "caption": "(a) Ser 317/Ser 777 is required for Ulk1 to protect cells from glucose starvation. Viability (24 h, mean ± s.d., n = 4; top) and PARP cleavage (8 h; western blot, middle; quantification, n = 2, bottom) was examined in Ulk1+/+ (WT), Ulk1−/− (KO), Ulk1−/− re-expressing wild-type Ulk1 (KO-WT), and Ulk1−/− re-expressing Ulk1 S317/777A mutant (KO-S317/777A) MEFs. Arrows in western blots indicate non-cleaved and cleaved PARP.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(b) The Ulk1 S317/777A mutant is compromised in LC3 lipidation in response to glucose starvation. ULK1MEFs were cultured in MEFs-free medium for the indicated times. LC3-II level was determined by western blotting and the LC3-II accumulation was normalized by α-tubulin and quantified (bottom, n = 3, mean ± s.d.). A representative western blot was shown. The LC3 antibody used in this experiment seemed to preferentially recognise the lipid-modified form of LC3-II, which migrated faster on the gel.",
    "ncbi_link": "ULK1: 22241
Ulk1: 22241"
  },
  {
    "caption": "(c) The Ulk1 S317/777A mutant is defective in autophagosome formation. The indicated MEFs were starved of glucose (4 h) and the formation of GFP-LC3-positive autophagosomes was examined by confocal microscopy. GFP-LC3; green and DAPI; blue. Scale bar, 20 μm.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(d) Autophagy vacuole analysis by electron microscopy. Low-magnification images of Ulk1−/− (KO, upper left panel), Ulk1−/− reconstituted with wild-type Ulk1 (KO-WT, two middle panels with accompanying higher magnification images), and Ulk1−/− reconstituted with Ulk1 S317/777A (KO-S317/777A, lower left panel) are shown. High-magnification images of autophagosomes from KO-WT are shown in upper right and lower right panels. Autophagosome/autolysosome-like structures indicated by arrowheads on the lower-magnification images and arrows in higher-magnification images. Scale bars; lower-magnification, 1 μm; higher-magnification, 200 nm.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "Transcription level of ena1A (x), ena1B (▲), ena1C (○) and dedA (♦) relative to rpoB determined by RT-qPCR during 16 hours of growth of B. cereus strain NVH 0075-95. The dotted line represents the bacterial growth measured by increase in OD600. Of note, the transcription of ena1C was surprisingly higher than ena1A and ena1B, the major components of the isolated S-Ena (Fig EV2).",
    "ncbi_link": "ena1A: 
ena1B: 
ena1C: 
rpoB: 
dedA: 61579111"
  },
  {
    "caption": "Representative negative stain images of endospores of NVH 0075-95 mutants lacking ena1A, ena1B, or ena1C, as well as endospores of strains complemented with the respective ena subunit expressed from plasmid (i.e. pA, pAB and pC). The ena1B mutant was complemented with a plasmid carrying both ena1A and 1B (pAB) due to repeated failure to transform with a plasmid holding ena1B only. Inset are 2D class averages of Enas observed on the respective mutants. Knockout of ena1A, ena1B, or ena1C results in the loss of S-Ena, a phenotype that is restored by plasmid-based complementation.",
    "ncbi_link": "1B: 
ena1B: 
ena1C: 
ena1A: "
  },
  {
    "caption": "Number (top) and length (bottom) of Enas found on WT, mutant (∆ena1A, ∆ena1B, or ∆ena1C) and plasmid complemented (∆ena1A:pena1A, ∆ena1B:pena1AB, or ∆ena1C:pena1C) NVH 0075-95 endospores. Statistics: pair-wise Mann-Whitney U tests against WT (n: ≥18 spores; n: ≥50 Enas; ns: not significant, * p<0.05, ** p<0.01, *** p<0.001 and **** p<0.0001. ---: mean ± s.d.)",
    "ncbi_link": "ena1A: 
ena1AB: 
ena1B: 
ena1C: "
  },
  {
    "caption": " A MOAP-1 co-localizes with p62 in the cytoplasmic inclusion bodies upon proteasome inhibition. HCT116 cells were transfected with plasmid encoding GFP-MOAP-1 or GFP only control. 14 hours later, cells were treated with the proteasome inhibitor MG132 (5 µM) for 8 hours and analyzed by immunofluorescence (IF) with anti-GFP (in green) and anti-p62 (in red) antibodies. Data information: , nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "GFP: 
MOAP-1: 64112"
  },
  {
    "caption": " C MOAP-1 is recruited to the p62 bodies upon exposure to cellular stresses. LO2 hepatocytes were transfected with plasmid encoding Myc-MOAP-1. 14 hours later, cells were then treated with MG132 (5 µM), arsenic trioxide (As2O3, 10 µM) or diethylnitrosamine (DEN, 200 µM) for 8 hours each. Cells were then processed for IF analysis with anti-Myc (in green) and anti-p62 (in red) antibodies. Data information: nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " D MOAP-1 spontaneously localizes to the p62 bodies at resting state in the liver cancer cell lines, HepG2, Huh-1, JHH5 and JHH7. The liver cancer cell lines were transfected with the plasmid encoding Myc-MOAP-1. 14 hours later, transfected cells were subjected to IF analysis with anti-Myc (in green) and anti-p62 (in red) antibodies. Data information: nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " E Absence of the aggregated patterns of MOAP-1 in the p62 deficient cells. WT and p62 KO HepG2 cells were transfected with plasmid encoding Myc-MOAP-1 for 14 hours and the cells were subjected to IF analysis as in (D). Data information: , nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " F Western blotting analysis of p62 and Myc-MOAP-1 protein levels in the WT and p62 KO HepG2 cells as described in (E). Actin as loading control. ",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": " A MOAP-1 downregulates the levels of the diethylnitrosamine (DEN)-induced p62 bodies in a time-dependent manner. LO2 cells were transfected with plasmid encoding Myc-MOAP-1. 14 hours later, cells were treated with DEN (200 µM) for the indicated period of times, before being subjected to IF with anti-Myc (in green) and anti-p62 (in red) antibodies. Cells expressing Myc-MOAP-1 were marked by dashed lines. Data information: nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " B MOAP-1 downregulates the p62 bodies in the resting HepG2 liver cancer cells. HepG2 were transfected with plasmid encoding Myc-MOAP-1. At the indicated time post-transfection, transfected cells were subjected to IF as in (A). Data information: nuclei were counterstained with DAPI (blue) ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " C Loss of MOAP-1 leads to spontaneous elevation of the basal levels of p62 bodies in the LO2 cells. WT, MOAP-1 KO and p62 KO LO2 cells were subjected to IF with anti-p62 antibody (in red). p62 KO cells were included as a negative control. Insets in the upper panels are enlarged in the lower panels. D Quantification of the p62 bodies in the WT and MOAP-1 KO LO2 cells. (Left panel) number of p62 bodies per cell. n = 7 independently plated samples. (Right panel) size of p62 bodies. n = 442 and 1014 bodies detected in the WT and MOAP-1 KO LO2 cells, respectively, from three independently plated samples. Data information: nuclei were counterstained with DAPI (blue)",
    "ncbi_link": "MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " E Re-expression of MOAP-1 reduces levels of p62 bodies in the MOAP-1 deficient LO2 cells. MOAP-1 KO LO2 cells were transfected with plasmid encoding Myc-MOAP-1 for 24 hours and subjected to IF with anti-p62 (in red) and anti-Myc (green) antibodies. Cells expressing Myc-MOAP-1 were marked by dashed lines. F Quantification of the p62 bodies in the MOAP-1 KO LO2 cells re-introduced with Myc-MOAP-1. (Left panel) number of p62 bodies per cell. n = 7 independently plated samples of MOAP-1 KO cells transfected with empty vector control (Ctrl) or plasmid encoding Myc-MOAP-1. (Right panel) size of p62 bodies. n = 178 and 69 bodies detected in the Ctrl and Myc-MOAP-1 expressing cells, respectively, from three independently plated samples. Data information: , nuclei were counterstained with DAPI (blue)",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " G Increased level of p62 bodies in MOAP-1 KO MEFs upon treatment with arsenic trioxide. WT and MOAP-1 KO MEFs were treated with arsenic trioxide (As2O3, 10 µM) for the indicated durations and subjected to IF with anti-p62 antibody (in red). H Quantification of the p62 bodies in the WT and MOAP-1 KO MEFs treated with arsenic trioxide. (Left panel) number of p62 bodies per cell. n ≥ 6 independently plated samples. (Right panel) size of p62 bodies. n = 10 (WT, basal), 17 (MOAP-1 KO, basal), 104 (WT, As2O3 2h), 137 (MOAP-1 KO, As2O3 2h), 605 (WT, As2O3 4h), 977 (MOAP-1 KO, As2O3 4h), 721 (WT, As2O3 6h) and 487 bodies (MOAP-1 KO, As2O3 6h) from three independently plated samples. Data information: nuclei were counterstained with DAPI (blue)",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " I MOAP-1 deficiency does not alter total protein levels of p62 in the LO2 cells. Western blotting analysis of p62 protein levels in the WT, MOAP-1 KO and p62 KO LO2 cells lysed in 1x Laemmli sample buffer containing 2% SDS. Actin as loading control. ",
    "ncbi_link": "MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " J MOAP-1 deficiency does not affect total protein levels of p62 in MEFs under basal and As2O3-treated conditions. Western blotting analysis of p62 and MOAP-1 in the WT and MOAP-1 KO MEFs treated with As2O3 as indicated. MOAP-1 was immunoprecipitated from the lysates. Actin as loading control. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " K Loss of MOAP-1 does not alter protein turnover of p62 in the LO2 cells. WT and MOAP-1 KO LO2 cells stably expressing Halo-tagged p62 were subjected to TMR labelling and harvested at the time points post-labelling as indicated. TMR signals of Halo-p62 were visualized by a Bio-rad Imager at 565 nM wavelength, whereas the total Halo-p62 protein was detected by Western blotting using anti-Halo or anti-p62 antibodies. L Quantification of the TMR signals in the WT and MOAP-1 KO LO2 cells by densitometric analysis. Average integrated density values of the TMR signals from three independent experiments were presented, relative to the levels at 0 hour. ",
    "ncbi_link": "MOAP-1: 64112"
  },
  {
    "caption": " A Overexpression of MOAP-1 downregulates levels of p62 bodies in the ATG5-depleted cells. HepG2 cells were infected with lentivirus encoding short hairpin RNA for ATG5 (shATG5) or scramble control (shCtrl) for 48 hours before being transfected with Myc-MOAP-1 or empty vector (EV) control for 24 hours and subjected to IF analysis using anti-p62 (in red) and anti-Myc (in green) antibodies. Cells expressing Myc-MOAP-1 were marked by dashed lines. B Quantification of the p62 bodies in the ATG5-depleted cells transfected with Myc-MOAP-1 or empty vector. (Upper panel) number of p62 bodies per cell. n ≥ 3 independently plated samples. (Lower panel) size of p62 bodies. n = 135, 133 and 65 bodies in the shCtrl+EV, shATG5+EV and shATG5+Myc-MOAP-1 cells, respectively, from three independently plated samples. Data information: nuclei were counterstained with DAPI (blue)",
    "ncbi_link": "Myc: 
ATG5: 9474
MOAP-1: 64112"
  },
  {
    "caption": " C Western blotting of the lysates from HepG2 cells infected with lentivirus encoding shATG5 or shCtrl and transfected with Myc-MOAP-1. ",
    "ncbi_link": "Myc: 
ATG5: 9474
MOAP-1: 64112"
  },
  {
    "caption": " D Inhibition of the auto-lysosomal degradation pathway does not prevent MOAP-1-mediated reduction of the p62 bodies. MOAP-1 KO LO2 cells were pre-treated with auto-lysosome inhibitors chloroquine (CQ) (10 µM) or BafA1 (1 µM) for 3 hours, before being transfected with Myc-MOAP-1 for 24 hours in the presence of CQ or BafA1 and subjected to immunofluorescence using anti-p62 (in red) and anti-Myc (in green) antibodies. Cells expressing Myc-MOAP-1 were marked by dashed lines. E Quantification of the p62 bodies in the MOAP-1 KO LO2 cells pre-treated with CQ or BafA1 before being transfected with Myc-MOAP-1 or empty vector control. (Upper panel) number of p62 bodies per cell. n = 5 independently plated samples. (Lower panel) size of p62 bodies. n = 362 (Ctrl, BafA1), 226 (Myc-MOAP-1, BafA1), 544 (Ctrl, CQ) and 266 bodies (Myc-MOAP-1, CQ), from three independently plated samples. Data information: nuclei were counterstained with DAPI (blue), ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " F Western blotting of lysates from MOAP-1 KO LO2 cells pre-treated with CQ or BafA1 and transfected with Myc-MOAP-1. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " A Larger RFP-p62 bodies in the MOAP-1 deficient cells. WT and MOAP-1 KO LO2 cells were transfected with expression vector encoding RFP-tagged p62. 16 hours later, cells were subjected to live imaging analysis. Z-stacks of the confocal images were flattened as maximal intensity projections. Scale bar: 5 µm. B Quantification of size of RFP-p62 bodies in WT and MOAP-1 KO LO2 cells. n = 129 and 161 bodies in the WT and MOAP-1 KO cells, respectively, from three independently plated samples. ***P<0.001, student's t-test. ",
    "ncbi_link": "RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " C Western analysis of lysates of the WT and MOAP-1 KO LO2 cells transfected with expression vector encoding RFP-tagged p62 as in (A). ",
    "ncbi_link": "RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " D, E RFP-p62 bodies exhibited fusion (D) and fission (E) characteristics of liquid droplets. WT and MOAP-1 KO LO2 cells were transfected with expression vector encoding RFP-tagged p62 and 14 hours later, cells were analyzed by live-imaging to visualize the dynamics of RFP-p62 bodies. Scale bar: 2 µm ",
    "ncbi_link": "RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " F Loss of MOAP-1 leads to slower exchange of p62 in the RFP-p62 bodies. WT and MOAP-1 KO LO2 cells transfected with expression vector encoding RFP-tagged p62. 14 hours later, cells were subjected to the fluorescence recovery after photobleaching (FRAP) assay. Scale bar: 2 µm. G Quantification of the rate of fluorescence recovery of RFP-p62 in WT and MOAP-1 KO cells. n = 5 samples. ",
    "ncbi_link": "RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " H Overexpression of MOAP-1 but not GFP leads to increased exchange of p62 in the RFP-p62 bodies. HepG2 cells were transfected with expression vector encoding RFP-tagged p62 and GFP-tagged MOAP-1 or GFP only control and 14 hours later, cells were subjected to FRAP assay. Scale bar: 2 µm. I Quantification of the rate of fluorescence recovery of RFP-p62 in HepG2 cells co-expressing GFP-MOAP-1 or GFP. n = 5 samples. ",
    "ncbi_link": "GFP: 
GFP.: 
RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " J Re-introduction of MOAP-1 disrupts the spherical structure of p62 bodies in the MOAP-1 deficient LO2 cells. MOAP-1 KO LO2 cells were transfected with expression vector encoding Myc-MOAP-1 and harvested at 14- or 24-hours post-transfection for IF analysis using anti-p62 (in red) and anti-Myc (in green) antibodies. Insets were enlarged in the lower panels. Scale bar: 2 µm. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " A MOAP-1 associates with p62 and their interaction is enhanced by DEN-mediated stress. LO2 cells transfected with Myc-MOAP-1 were treated with or without diethylnitrosamine (DEN) (200 µM) for 12 h and subjected to Duolink proximity ligation assay using anti-p62 and anti-Myc antibodies. Red dots represent MOAP-1/p62 interaction. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " B Alanine substitution of positively charged residues in the KYKKLR sequence of MOAP-1 abolishes its interaction with p62. Replacement of the positively charged residues in the KYKKLR sequence of MOAP-1 with alanine (referred to as the M3 mutant) disrupts MOAP-1/p62 interaction, whereas alanine substitution in the neighboring region of positively charged KRRR (M1 mutant) and negatively charged EEE (M2 mutant) has no effect. LO2 cells were transfected with plasmid encoding Myc-MOAP-1 or the indicated alanine mutants together with plasmid encoding Flag-p62. The cells were then subjected to co-IP assay with anti-Myc antibody. ",
    "ncbi_link": "Flag: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " D MOAP-1, but not its p62-binding defective mutant, MOAP-1-M3, localizes at the p62 bodies. MOAP-1 KO LO2 cells were transfected with plasmid encoding Myc-MOAP-1 or Myc-MOAP-1-M3 mutant. The transfected cells were harvested at 14 hours post-transfection, which is the time point that localization of MOAP-1 at the p62 bodies is readily detected. IF analysis was performed on these cells using anti-p62 (red) and anti-Myc (green) antibodies. Arrowheads indicate colocalization between Myc-MOAP-1 and p62 bodies. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " E MOAP-1 but not the MOAP-1-M3-mutant promotes the exchange of RFP-p62 in the p62 bodies. WT LO2 cells transfected with expression vector encoding RFP-tagged p62 and GFP-tagged MOAP-1 or MOAP-1-M3. At 14 hours post-transfection, cells were subjected to FRAP assay. Scale bar: 2 µm. ",
    "ncbi_link": "GFP: 
RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": "F Quantification of the rate of fluorescence recovery of RFP-p62 in cells co-expressing GFP-MOAP-1 or GFP-MOAP-1-M3 mutant. n = 6 samples. Error bars represent S.E.M. *P<0.05, **P<0.01, ns, not significant, two-way ANOVA.",
    "ncbi_link": "GFP: 
MOAP-1: 64112"
  },
  {
    "caption": " G Western analysis of lysates of the WT LO2 cells transfected with expression vector encoding RFP-tagged p62 and GFP-tagged MOAP-1 or MOAP-1-M3 as described in (E). ",
    "ncbi_link": "GFP: 
RFP: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " H Re-expression of MOAP-1, but not the MOAP-1-M3 mutant, reduces the levels of p62 bodies. MOAP-1 KO LO2 cells were transfected with plasmid encoding Myc-MOAP-1 or Myc-MOAP-1-M3. The transfected cells were harvested at 24 hours post-transfection, which is the time point that MOAP-1 was found to effectively downregulate p62 bodies, followed by IF analysis as in (D). Cells expressing Myc-MOAP-1 or Myc-MOAP-1-M3 were marked by dashed lines. I Quantification of the p62 bodies in the MOAP-1 KO LO2 cells expressing Myc-MOAP-1 and Myc-MOAP-1-M3 mutant. (Left panel) number of p62 bodies per cell. n = 7 independently plated samples. (Right panel) size of p62 bodies. n = 107 and 267 bodies detected in the MOAP-1 KO LO2 cells expressing Myc-MOAP-1 and Myc-MOAP-1-M3 mutant, respectively, from three independently plated samples. Error bars represent S.E.M. ***P<0.001, Student's t-test. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " J Western blotting of MOAP-1 KO LO2 cells transfected with plasmid encoding Myc-MOAP-1 or Myc-MOAP-1-M3 mutant as described in (H). ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " A Overexpression of MOAP-1 inhibits dimerization of p62. p62 KO LO2 hepatocytes were transfected with the indicated plasmids. 24 hours later, cell lysates were subjected to co-IP assay with anti-Myc antibody. PB1 deletion (ΔPB1) mutant, which is impaired in p62 oligomerization, is included as a control. TCL, total cell lysates. ",
    "ncbi_link": "MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " B Dimerization of p62 is enhanced in the MOAP-1 deficient cells. WT and MOAP-1 KO LO2 cells were transfected with plasmids encoding Flag-tagged and Myc-tagged p62 or empty vector. 24 h post-transfection, cells were harvested, lysed and the cell lysates were subjected to co-IP assay with anti-Myc antibody. C Quantification of the levels of Flag-p62 bound to Myc-p62 in the co-IP experiment as described in (B) by densitometric analysis. ",
    "ncbi_link": "Flag: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " D Re-expression of MOAP-1, but not the p62-binding defective mutant, MOAP-1-M3, reduces p62 oligomerization in the MOAP-1 KO LO2 hepatocytes. WT and MOAP-1 KO LO2 cells were transfected with plasmids encoding His-tagged p62 and Myc-MOAP-1 or Myc-MOAP-1-M3 and 24 h later, subjected to His-pull down and cross-linking using DSSO. E Quantification of the levels of p62 oligomer depicted in (D) by densitometric analysis. ",
    "ncbi_link": "His: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " F The region of p62 spanning the PB1 and ZZ domains are required for mediating its interaction with MOAP-1. p62 KO LO2 cells were used in the analysis. Cells were transfected with plasmid encoding Myc-p62 or the indicated deletion mutants and Flag-MOAP-1 for 24 hours. The transfected cells were subjected to co-IP assay with anti-Myc antibody. (Lower panel) Schematics depicting the domains in p62. PB1, Phox and Bem1p; ZZ, Zinc Finger; TB, TRAF6-binding domain; KIR, Keap1 interacting region; LIR, LC3 interacting region; UBA, ubiquitin-associated domain. ",
    "ncbi_link": "Flag: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " G The fragment encompassing the PB1 and ZZ domains of p62 is sufficient for mediating its interaction with MOAP-1. p62 KO LO2 cells were transfected with plasmid encoding Myc-p62 or the indicated fragments and Flag-MOAP-1. 24 hours later, the transfected cells were subjected to co-IP assay with anti-Myc antibody. ",
    "ncbi_link": "Flag: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " H MOAP-1 binds and inhibits homodimerization of the PB1-ZZ fragment. p62 KO LO2 cells were transfected with plasmid encoding Myc and Flag-tagged PB1-ZZ in the absence of presence of HA-tagged MOAP-1 for 24 h and subjected to co-IP assay with anti-Myc antibody. ",
    "ncbi_link": "Flag: 
HA: 
Myc: 
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " A Increased recruitment of Keap1 to p62 bodies in the MOAP-1 deficient LO2 cells. WT and MOAP-1 KO LO2 cells were subjected to IF analysis with anti-Keap1 (green) and anti-p62 (red) antibodies. Insets in the upper panels are enlarged in the lower panels. Nuclei were counterstained with DAPI (in blue). Scale bar: 5 µm. ",
    "ncbi_link": "MOAP-1: 64112"
  },
  {
    "caption": " B MOAP-1 deficiency promotes p62/Keap1 interaction. WT, MOAP-1 KO and p62 KO LO2 cells were subjected to co-IP assay using anti-p62 antibody. TCL, total cell lysates. C Quantification of the levels of Keap1 bound to p62 in the co-IP experiment as described in (B) by densitometric analysis. ",
    "ncbi_link": "MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " D Diminished Keap1/Nrf2 interaction in the absence of MOAP-1. WT and MOAP-1 KO LO2 cells were subjected to Duolink PLA using anti-Keap1 and anti-Nrf2 antibodies. Red dots represent Keap1/Nrf2 interaction. Nuclei were counterstained with DAPI (in blue). Scale bar: 10 µm. E Quantification of the Duolink signals depicted in (D). Duolink signals, which appear as red dots, were quantified by ImageJ analysis and normalized to the number of nuclei. ",
    "ncbi_link": "MOAP-1: 64112"
  },
  {
    "caption": " F Loss of MOAP-1 results in marked elevation of nuclear Nrf2. WT and MOAP-1 KO LO2 cells were subjected to IF analysis with anti-Nrf2 (in green) and anti-p62 (in red) antibodies. Scale bar: 10 µm. G Quantification of nuclear levels of Nrf2 in (F). The mean gray values of Nrf2 fluorescence signals were quantified by ImageJ analysis. ",
    "ncbi_link": "MOAP-1: 64112"
  },
  {
    "caption": " H MOAP-1 deficiency promotes activation of Nrf2 signaling. Transcript levels of downstream targets of Nrf2 (i.e. HMOX-1, NQO1, SLC7A11, GCLC and G6PD) in WT and MOAP-1 KO LO2 cells were determined by RT-PCR and normalized to GAPDH. ",
    "ncbi_link": "G6PD: 2539
GAPDH: 2597
GCLC: 2729
HMOX-1: 3162
Nrf2: 9817
MOAP-1: 64112
NQO1: 1728
SLC7A11: 23657"
  },
  {
    "caption": " I Elevated transcriptional activity of Nrf2 in the MOAP-1 deficient cells is mediated through p62. Transcript levels of Nrf2 target genes (HMOX-1 and NQO1) in WT, MOAP-1 KO and MOAP-1/p62 DKO LO2 cells were determined by RT-PCR and normalized to GAPDH. ",
    "ncbi_link": "GAPDH: 2597
HMOX-1: 3162
Nrf2: 9817
MOAP-1: 64112
NQO1: 1728
p62: 8878"
  },
  {
    "caption": " J Re-expression of MOAP-1 and MOAP-1-L120E, but not the p62 binding defective mutant of MOAP-1, MOAP-1-M3, inhibits p62/Keap1 interaction in the MOAP-1 deficient cells. MOAP-1 KO LO2 cells were transfected with plasmid encoding Myc-tagged MOAP-1, L120E or M3. The transfected cells were then subjected to co-IP assay with anti-p62 antibody. ",
    "ncbi_link": "Myc: 
MOAP-1: 64112"
  },
  {
    "caption": " K Re-introduction of MOAP-1 and MOAP-1-L120E, but not the p62 binding defective MOAP-1-M3, reduces Nrf2 transcriptional activity in the MOAP-1 KO cells. MOAP-1 KO LO2 cells were transfected with Myc-tagged MOAP-1, MOAP-1-L120E or MOAP-1-M3 and ARE-Nrf2-firely and renilla luciferase reporter constructs for overnight and subjected to luciferase assay. ",
    "ncbi_link": "luciferase: 
Myc: 
Nrf2: 9817
MOAP-1: 64112
p62: 8878"
  },
  {
    "caption": " A High level of p62 bodies in the liver of the MOAP-1 KO mice subjected to acute diethylnitrosamine (DEN) treatment. Eight-week-old male WT and MOAP-1 KO mice were injected with an acute dose of DEN (100 µg/g body weight). Mice were sacrificed at 48 hours post-injection. Livers were harvested for immunohistochemistry (IHC) analysis with anti-p62 antibody (in red). Nuclei were counterstained with DAPI (in blue). Insets in the upper panels are enlarged in the lower panels. Scale bar: 20 µm. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " B Loss of MOAP-1 results in higher levels of Nrf2 and its downstream target protein, HMOX-1, in liver upon acute DEN treatment. Lysates of the livers harvested from mice subjected to acute DEN treatment as described in (A) were prepared in RIPA lysis buffer containing 1% SDS and analyzed by Western blotting. Actin as loading control. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " C MOAP-1 deficiency elevates levels of p62 protein in the detergent-insoluble fractions of the liver lysates from mice subjected to acute DEN treatment. Livers from mice injected as described in (A) were lysed in 1% Triton-X lysis buffer, separated into detergent-soluble (S) and insoluble (I) fractions and analyzed by Western blotting. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " D High levels of p62 bodies detected in the tumors of the MOAP-1 KO mice. Tumor sections from livers dissected from the 8.5-month-old male WT and MOAP-1 KO mice injected with a single dose of DEN (25 µg/g body weight) at 15-day-old were subjected to IHC analysis with anti-p62 antibody (in red). Nuclear were stained with DAPI (in blue). Insets were enlarged in the bottom right. Scale bar: 20 µm. E Quantification of the p62 bodies in the WT and MOAP-1 KO tumors. (Left panel) number of p62 bodies per cell. n = 7 tumors from the livers of WT and MOAP-1 KO mice. (Right panel) size of p62 bodies. n = 456 and 1211 bodies detected in the WT and MOAP-1 KO tumors, respectively, from three independent samples. Error bar represents S.E.M. *P<0.05, ***P<0.001, student's t-test. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " F Increased levels of Nrf2 and its downstream target protein, HMOX-1, in the MOAP-1 deficient tumors. While p62 protein is upregulated in the tumors compared to the adjacent non-tumor tissues in both WT and MOAP-1 KO livers, no significant difference is observed in the p62 protein levels between the WT and MOAP-1 KO tumors. Lysates of the tumors and non-tumor parts of the livers from mice injected with DEN as described in (D) were prepared in RIPA lysis buffer containing 1% SDS and subjected to Western blotting. Actin as loading control. P, PBS injected control; N, non-tumor; T, tumor. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " G Upregulation of mRNA levels of HMOX-1 and NQO1 in the MOAP-1 deficient tumors. Livers harvested from the mice injected with PBS or DEN as described in (D) were subjected to RT-PCR analysis. n = 3 WT and 3 MOAP-1 KO mice injected with the PBS control, and 8 WT and 9 MOAP-1 KO mice injected with DEN. Error bar represents S.E.M. **P<0.01, student's t-test. ",
    "ncbi_link": "HMOX-1: 15368
MOAP-1: 64113
NQO1: 18104"
  },
  {
    "caption": " H MOAP-1 deficient mice bear higher tumor burden in the DEN-mediated liver cancer model. Representative images of liver tumors dissected from the 8.5-month-old male WT and MOAP-1 KO mice injected with a single dose of DEN (25 µg/g body weight) at 15-day-old. Scale bar: 5 mm. I Measurements of the number, maximum diameter of the tumor nodules and total liver weight from WT and MOAP-1 KO mice (n=13 and 14 respectively) injected with DEN as described in (H). Error bar represents S.E.M. **P<0.01, ***P<0.001, student's t-test. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": " MOAP-1 deficiency promotes tumor initiation. measurements of the number, diameter of the largest nodules and total liver weight of the 4.5-month-old WT and MOAP-1 KO mice (n=18 and 23 respectively) injected with a single dose of DEN (25 µg/g body weight) at 15-day-old. ",
    "ncbi_link": "MOAP-1: 64113"
  },
  {
    "caption": "Gene expression level of IL-1β and IL-6 of indicated mouse lung with PAO1 infection (5 × 106 CFU) for 6 h and 24 h. n≥3. Error bars, S.E.M. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.",
    "ncbi_link": "IL-1β: 16176
IL-6: 16193"
  },
  {
    "caption": "Histogram of selected differentially expressed genes of LL-37+/+ mouse lung versus wild type FVB mouse lung prior to infection. Blue bars indicated genes up-regulated in wild type FVB mouse lungs, red bars indicated genes up-regulated in LL-37+/+ mouse lungs.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Detection of LL-37 expression in the engineered mDASCs by real-time quantitative PCR",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Anti-Krt5 (red) and anti-P63 (green) immunostaining of WT- and LL-37-mDASC colonies. Scale bar, 70 μm.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Stem cell colony-forming efficiency of WT- and LL-37-mDASCs during 5 serial passages. n=6.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Bright field and direct fluorescence images of mouse lungs following transplantation of 1 × 106 GFP-labeled WT-mDASCs (WT-Lung) or LL-37-mDASCs (LL-37-Lung) on indicated days. Scale bar, 1000 μm",
    "ncbi_link": "GFP: 
LL-37: 820"
  },
  {
    "caption": "Anti-Ki67 immunofluorescence of engrafted GFP-labeled WT- and LL-37-mDASCs in lung parenchyma 21 days after transplantation. Scale bar, 50 μm.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Distribution of engrafted GFP-labeled cells in lung parenchyma by immunofluorescence 7 days after transplantation. WT-Lung: WT-mDASCs engrafted; LL-37-Lung: LL-37-mDASCs engrafted. Scale bar, 200 μm. Arrows showed the representative cells with overlapping fluorescence of GFP and LL-37.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Intratracheal instillation of equal amount of PAO1(5 ×106 CFU per mouse) into WT-Lung (WT-mDASCs engrafted) and LL-37-Lung (LL-37-mDASCs engrafted) followed by bacterial CFU analysis in whole lung homogenates 6, 24 and 48 hours after infection. n=3. Error bars, S.E.M. Intratracheal instillation of equal amount of PAO1 into WT-Lung and LL-37-Lung followed by bacterial CFU analysis in BAL fluid 6, 24 and 48 hours after infection. n=3. Error bars, S.E.M.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Arterial blood gas analysis of mice with WT-Lung and LL-37-Lung following PAO1 infection. n=6. Error bars, S.E.M. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "H&E staining showing histology of injured lung infected by PAO1 with WT-mDASCs or LL-37-mDASCs transplantation. Scale bar, 100 μm. Histopathological examination according to the lung injury scoring system based on blinded expert judgement. n=5 mice per group. Error bars, S.E.M.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "CD68 immunochemistry (brown) in infected lung with WT-mDASCs or LL-37-mDASCs transplantation. Scale bar, 50 μm. Quantification of brown-stained (CD68+) area by Image J software. n=5. Error bars, S.E.M.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Gene expression level of indicated pro-inflammatory cytokines of lung infected by PAO1 with WT-mDASCs or LL-37-mDASCs transplantation. n=3. Error bars, S.E.M. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "The mRNA expression levels of LL-37 was measured by qPCR for WT- and LL-37-hDASCs. n=5. Error bars, S.E.M.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "Ex vivo biomimetic culture of LL-37-hDASCs recellularized lungs with constant media perfusion.",
    "ncbi_link": "LL-37: "
  },
  {
    "caption": "The recellularized lung by LL-37-hDASCs displayed growth inhibitory effect on PAO1 and E.coli. Initial dose of bacteria was 2× 104 CFU. Culture duration, 24h. n=6. Error bars, S.E.M. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.",
    "ncbi_link": "LL-37: 820"
  },
  {
    "caption": "(A) Levels of Piwil1  (Miwi), Piwil2  (Mili) and Piwil4  (Miwi2) transcripts in RNA seq. data from undifferentiated aNPCs  (Days of differentiation -DIF- 0) and differentiating neuroblasts  (DIF 4-14); insets in left and right panels show the same data with smaller scales in the ordinate axes. Data information: data are expressed as mean ± SEM, n = 3 biological replicates.",
    "ncbi_link": "Miwi: 57749
Piwil1: 57749
Mili: 57746
Piwil2: 57746
Miwi2: 330890
Piwil4: 330890"
  },
  {
    "caption": "(G) Scheme of the experiment (top) and Mili  mRNA expression  in sorted Td+ and Td- cells after in vivo transduction with split-Cre  viruses in the hippocampus  (bottom). Data information: data are expressed as mean ± SEM, n = 3 biological replicates. *p < 0.05, **p < 0.01, **** p < 0.0001 as assessed by one-way ANOVA with Bonferroni test G)",
    "ncbi_link": "Cre: 2777477
Mili: 57746"
  },
  {
    "caption": "(E) Mili  mRNA expression  (left bar graph); western blot (inset) and quantification (right bar graph) of Mili  protein abundance in aNPCs upon viral transduction of scrambled shRNA (Control) or shRNA targeting Mili  (Mili  KD). Data information: data are expressed as mean ± SEM unless differently indicated, n = 3 biological replicates ∗p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test.",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "(C) Mili  mRNA expression  (left bar graph); western blot (inset) and quantification (right bar graph) of Mili  protein abundance in lysates from the DG  of mouse hippocampi  48 hours after the injection of scrambled (Control) or GapmeR1 against Mili  (Mili  KD). Data information: data are expressed as mean ± SEM, n = 3 (C, biological replicates. ∗p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test.",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "(E) Representative immunofluorescence  micrograph of postnatal hippocampal  sections immunostained  for GFAP  at 30 dpi of scrambled (Control) and GapmeR1 against Mili  (Mili  KD); Right panels: Fold change in GFAP  fluorescence intensity level (upper graph) in a hippocampal  region of interest (ROI) of 500µm2 in brain  slices upon Mili  KD compared to Control; Gfap  mRNA levels (lower graph) in the DG  from mouse hippocampi  48 hours after the injection of scrambled (Control) or GapmeR1 (Mili  KD). Data information: data are expressed as mean ± SEM, n = 3 E mRNA and 5 (E biological replicates. ∗p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test. SGZ, subgranular zone. The scale bars represent 100 µm (E,",
    "ncbi_link": "Gfap: 14580
Mili: 57746"
  },
  {
    "caption": "(F) (Left) representative immunofluorescence  micrograph of postnatal hippocampal  sections immunostained  for GFAP  (green), BrdU  (red), NeuN  (white) and nuclear DNA  (blue) at 30 dpi of scrambled (Control) or GapmeR1 against Mili  (Mili  KD); (right graphs) percentages of NeuN+BrdU+ (white arrowheads in the images), or GFAP+BrdU+ (yellow arrowheads in the images) double-positive cells over total BrdU+ cells. Data information: data are expressed as mean ± SEM, n = F) biological replicates. ∗p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test. GCL, granular cell layer, SGZ, subgranular zone. The scale bars represent 100 µm F).",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "(B) Representative bright-field microscopy images (left) and quantification (right) of  ß-galactosidase+ aNPCs as percent of total cells upon Mili  KD, or control 48 h after induction of spontaneous differentiation. Data information: data are expressed as mean ± SEM, n = 5 (B biological replicates p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test. The scale bars represent 50 µm (B,",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "(C) Representative  fluorescence microscopy images (left) and quantification (right) of control or Mili  KD neuroblasts  48h after spontaneous differentiation, immunostained  with anti-BrdU  (white) and Ki67  (purple) antibodies. (Right) Percentage of BrdU+ and Ki67- cells over BrdU+ cells. Data information: data are expressed as mean ± SEM, n = C) biological replicates p < 0.05, ∗∗p < 0.01, *** p < 0.001, **** p < 0.0001, as assessed by two-tailed Student's t-test. The scale bars represent 50 µm C)",
    "ncbi_link": "Mili: 57746"
  },
  {
    "caption": "(C) Expression  levels of human GRα   and LRH-1 mRNA in human T-ALL  cell lines were determined by probe-based real-time quantitative PCR, calculated as relative expression  compared to  beta-actin and used to determine the GR:LRH-1 ratio (right). Individual and mean values of four biological replicates ± SD are shown and statistically significant differences between CEM-C7  and GC-resistant cell lines were determined by one-way ANOVA.",
    "ncbi_link": "beta-actin: 60
GR: 2908
GRα: 2908
LRH-1: 2494"
  },
  {
    "caption": "(F) GR  activity in human T-ALL  cells transfected with a control luciferase  reporter plasmid (pGL3) (F) GR  responsive (GRE) luciferase  reporter and treated with 3d2  and/or Dexa.  β-galactosidase  (bGal) was co-transfected as an internal transfection control. Luciferase reporter activity was normalized to bGal  activity and calculated as relative to the DMSO-treated pGL3 control. Individual and mean values analyzed by two-way ANOVA of three biological replicates ± SD are shown for Jurkat  and CEM-C7  whereas technical triplicates ± SD of a representative experiment (n=3 biological replicates) are shown for MOLT-4. Data information: For all displayed experiments dimethyl sulfoxide  (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "luciferase: 
bGal: 2720
β-galactosidase: 2720"
  },
  {
    "caption": "(G) LRH-1  activity in human T-ALL cells transfected with a control luciferase  reporter plasmid (pGL3) and (G) LRH-1 responsive (5xRE) luciferase  reporter and treated with 3d2 β-galactosidase (bGal) was co-transfected as an internal transfection control.  Luciferase reporter activity was normalized to bGal  activity and calculated as relative to the DMSO-treated pGL3 control. Individual and mean values analyzed by two-way ANOVA of three biological replicates ± SD are shown for Jurkat  and CEM-C7 whereas technical triplicates ± SD of a representative experiment (n=3 biological replicates) are shown for  MOLT-4. Data information: For all displayed experiments dimethyl sulfoxide (DMSO; was used as a solvent control. ns = not significant, * p < 0.05, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "luciferase: 
bGal: 2720
β-galactosidase: 2720"
  },
  {
    "caption": "(B) Daily cell counting-based comparison of cellular proliferation   of  T-ALL  cells after (B) small hairpin RNA-mediated LRH-1  knockdown (shLRH-1). Individual and mean values of technical triplicates of one representative experiment (n=3 biological replicates) ± SD anlyzed by two-way ANOVA are shown. Data information: ns = not significant, * p < 0.05, *** p < 0.001.",
    "ncbi_link": "LRH-1: 2494"
  },
  {
    "caption": "(F)  Flow cytometric  analysis of 3d2-induced cell death by AnnexinV staining  in wild-type (WT), Bcl-2 overexpressing (Bcl-2) and Z-VAD-FMK (zVAD)-treated  CEM-C1. Mean values of technical triplicates of one representative experiment (n=3 biological replicates) ± SD analyzed by two-way ANOVA are shown. Data information: ns = not significant, * p < 0.05, *** p < 0.001.",
    "ncbi_link": "Bcl-2: 596"
  },
  {
    "caption": "(C) Flow cytometric  analysis of cell death  by AnnexinV staining  in control or Bim  knockout (Bim  KO) CEM-C7  cells treated with 3d2  and 30 µM Dexa. Mean values of technical triplicates of one representative of n=4 biological replicates ± SD are shown. Data information: Two-way ANOVA C, ns = not significant, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "Bim: 10018"
  },
  {
    "caption": "(D) Immunoblots  of BimEL, BimL  and BimS, Bcl-2 and Tubulin  from MOLT-4 expressing a non- (shcontrol) or LRH-1- (shLRH-1) targeting small hairpin RNA construct.",
    "ncbi_link": "LRH-1: 2494"
  },
  {
    "caption": "(E) Flow cytometric  analysis of  cell death by AnnexinV staining  in control or glucocorticoid receptor knockout (GR  KO) MOLT-4  cells treated with 3d2  and 30 µM Dexa. Mean values of n=3 biological replicates ± SD are shown. Data information: Two-way ANOVA E); ns = not significant, ** p < 0.01, *** p < 0.001.",
    "ncbi_link": "glucocorticoid receptor: 2908
GR: 2908"
  },
  {
    "caption": "(F/G) mRNA expression  levels of human GR (F) and Bim (G) in shcontrol and shLRH-1 CEM-C1 cells were determined by  real-time quantitative PCR after treatment with 1 µM Dexa  for indicated times. Fold induction relative to the untreated shcontrol sample (0h) was calculated after normalization to beta-actin. Individual values of technical triplicates of one representative of two biological replicates ± SD are shown. Data information: For all displayed experiments dimethyl sulfoxide (DMSO; represented by 0 was used as a solvent control.",
    "ncbi_link": "beta-actin: 60
Bim: 10018
GR: 2908
LRH-1: 2494"
  },
  {
    "caption": "(C) Expression  levels of human GRα, LRH-1 and Bim  mRNA in human  PDX were determined by real-time quantitative PCR, calculated as relative expression  compared to  beta-actin and used to determine the GR:LRH-1 ratio (right). Data information: All displayed experiments display one biological replicate.",
    "ncbi_link": "beta-actin: 60
Bim: 10018
GR: 2908
GRα: 2908
LRH-1: 2494"
  },
  {
    "caption": "(a-c) We used quantitative real-time PCR to determine the expression patterns of ATG5 (a), ATG7 (b) and ATG16L1 (c) in various human immune and epithelial cell lines. ATG5 was broadly expressed in the cell lines studied (a), with between 1.5- and fourfold variations in expression level across the cell lines. ATG7 expression (b) was broadly comparable to that of ATG5, with the exception of THP1 cells, which showed 35-fold higher expression than SW480 cells. ATG16L1 expression (c) was also broadly similar to that of ATG5 and ATG7 (except for ATG7 expression in THP1 cells), with moderate variations across the cell lines tested (1.5- to 3.5-fold).",
    "ncbi_link": "ATG16L1: 55054
ATG5: 9474
ATG7: 10533"
  },
  {
    "caption": "(d) Expression of ATG16L1 in human primary immune cells. In a resting human immune cell RNA panel (Clontech), ATG16L1 showed a clear peak of expression in the T cell compartment, with CD4+ and CD8+ cells expressing high levels of transcript (15- to 20-fold more than control samples). We detected modest levels of ATG16L1 in CD19+ cells and low levels in CD14+ monocytes and unfractionated mononuclear cells. In all cases, we performed real-time quantitative RT-PCR reactions in duplicate and plotted the means; error bars represent 1 s.d. We normalized expression levels by comparison with GAPDH controls and plotted arbitrary relative expression units, where the SW480 or placental RNA expression equals 1 (for cell lines or primary cells, respectively). We isolated all RNAs from resting cells in the absence of stimulation or activation.",
    "ncbi_link": "ATG16L1: 55054
GAPDH: 2597"
  },
  {
    "caption": "(a) We achieved specific siRNA knockdown of overexpressed, Flag-tagged ATG16L1 in HEK293 cells within 48 h of transfection with oligonucleotide duplexes. Flag-ATG16L1 was undetectable by protein blotting after treatment with specific siRNA constructs, but expression was maintained with control duplexes.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "(b) Endogenous ATG16L1 mRNA knockdown (mean relative abundance ± s.d.) by siRNA 2 in HeLa cells within 48 h of transfection, as assessed by real-time quantitative RT-PCR normalized to GAPDH. Compared with control duplex, siRNA 2 yielded an 89% reduction in transcripts. RT-PCR was performed in triplicate; results represent two independent experiments.",
    "ncbi_link": "ATG16L1: 55054
GAPDH: 2597"
  },
  {
    "caption": "c) Knockdown of ATG16L1 prevented effective autophagy of S. typhimurium in HeLa cells. Forty-eight hours after cotransfection with control siRNA or duplex 2 and LC3-GFP plasmid, HeLa cells were infected for 1 h with Salmonella typhimurium SL1344, fixed and examined microscopically. Mean percentages (± s.e.m.) of bacteria per cell encapsulated by LC3+ membranes (autophagosomes) are shown. Bacterial counts were pooled from two separate experiments; each counted a minimum of 100 infected cells. Significance was assessed by two-tailed Students t-test, assuming unequal variances.",
    "ncbi_link": "ATG16L1: 55054
LC3: 440738///81631///84557"
  },
  {
    "caption": "(d) Representative images of intracellular S. typhimurium show normal autophagic encapsulation by LC3+ membranes in control siRNA-treated cells but loss of autophagic targeting after ATG16L1 knockdown. Channels are separated to show both the LC3-GFP fusion protein (autophagosomal marker) and S. typhimurium SL1344 dsRed2 (SL1344), with a merged image in the final column. Rows 2 and 4 show magnified views of boxed areas in rows 1 and 3, respectively. Images were obtained using confocal microscopy and are a flat projection of z stacks taken throughout the plane of the infected cell. Scale bars = 5 μm.",
    "ncbi_link": "ATG16L1: 55054
LC3: 440738///81631///84557"
  },
  {
    "caption": "A. H3122 cells expressing endogenous EML4-ALK V1 and HEK293 transfected with YFP-EML4-ALK V1 WT and KD were stained for either anti-ALK or anti-GFP (green), anti-α-tubulin (red), and DAPI (blue). Scale bars, 10 μm; magnified views of a selected area are shown. B. Violin plots showing the number of EML4-ALK V1 cytoplasmic foci per cell. Data represents 30-50 counts from three biological replicates. ***P<0.001, ****P<0.0001 in comparison to HEK293 YFP-EML4-ALK-V1 KD by one-way ANOVA analysis. ",
    "ncbi_link": "YFP: 
ALK: 238
EML4: 27436"
  },
  {
    "caption": "C. H2228 cells expressing endogenous EML4-ALK V3 and HEK293 transfected with YFP-EML4-ALK V3 WT and KD were stained for either anti-ALK or anti-GFP (green), anti-α-tubulin (red), and DAPI (blue). Scale bars, 10 μm; magnified views of a selected area are shown. D. Violin plots showing the number of EML4-ALK V3 cytoplasmic foci per cell. Data represents 30-50 counts from four biological replicates. ***P<0.001, ****P<0.0001 in comparison to HEK293 YFP-EML4-ALK-V3 KD by one-way ANOVA analysis. ",
    "ncbi_link": "YFP: 
ALK: 238
EML4: 27436"
  },
  {
    "caption": "H. Whisker plot showing the calculated velocity of single events in the kymograph. Data represent 20 counts from 10 kymographs. n=2. Error bar represents SD of two biological replicates. *P< 0.05 in comparison to YFP EML4-ALK V3 KD by unpaired t test.",
    "ncbi_link": "YFP: 
ALK: 238
EML4: 27436"
  },
  {
    "caption": "A, B, C, D. HEK293 cells were transfected with EML4-ALK V1 WT or V3 WT or Kinase Dead (KD) for 48 hours. Cells were either untreated (DMSO) or treated with ALK inhibitors for 4 hours before fixation and staining with anti-GFP (green), anti-α-tubulin (red), and DAPI (blue). Scale bars, 10 μm; magnified views of a selected area are shown.",
    "ncbi_link": "ALK: 238
EML4: 27436"
  },
  {
    "caption": "(B)  Western blot analysis of the generated isogenic cell lines described in A after inducing GFP-TDP-43 expression for 48 h showing the tightness of the doxycycline  (DOX)-modulated expression system. Note also the different protein levels of the expressed variants. endTDP-43: endogenous TDP-43.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(D) GFP-TDP-43 expression was induced with DOX  for 24 h before cycloheximide  (CHX) treatment for the indicated times  and western blot analysis. (E) Quantification of the GFP  signal from D. N=3 independent experiments. Two-way ANOVA with Tukey's multiple comparisons post hoc test.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(B) Representative maximum intensity Z-projections from confocal  fluorescence imaging of human neurons  transduced with TDP-43-HA  variants and immunolabeled  for the HA  tag and the neuron-specific marker MAP2. Scale bar: 10 µm. Cell nuclei  are stained  with DAPI",
    "ncbi_link": "HA: 
TDP-43: 23435"
  },
  {
    "caption": "(D) GFP-TDP-43 expression was induced with doxycycline (DOX) for 4 h before nucleocytoplasmic  fractionation and subsequent analysis of GFP-TDP-43 and endogenous TDP-43 (endTDP-43) levels by  western blot. T: total lysate, C: cytoplasmic  fraction, N: nuclear  fraction. (E) Quantification of the GFP  signal from D. Repeated measures one-way ANOVA with Greenhouse-Geisser correction and Tukey's multiple comparisons post hoc test. Cyt: cytoplasm, Nuc: nucleus.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(C)  Fluorescence microscopy  images of 10 μM purified full-length TDP-43  and its oligomerization-deficient counterpart showing different abilities to undergo LLPS  and its disruption by 1,6-HD treatment for 10 min. Scale bar: 10 μm. (D) Quantification of the number of condensates in the conditions shown in C per 4000 µm2 field. N=10 independent experiments. Kruskal-Wallis test with Dunn's multiple comparisons post hoc test.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "(H) GFP-TDP-43  expression was induced with DOX  for 4 h before crosslinking protein-protein interactions with DSG  and subsequent analysis by  western blot. *, ** and *** indicate GFP-TDP-43 monomers, dimers and trimers, respectively. o, oo, ooo and oooo indicate endTDP-43 monomers, dimers, trimers and tetramers. ­­­(I) Quantification of GFP-TDP-43 dimer/monomer ratio based on the GFP  signal from H. N=3 independent experiments. Repeated measures one-way ANOVA with Greenhouse-Geisser correction and Tukey's multiple comparisons post hoc test. * p<0.05, ** p<0.01, **** p<0.0001. Graph bars represent mean ± SD.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(G) Quantification of the nuclear PLA  signal shown in F correlated to the protein expression  levels of the different TDP-43 variants, measured as the mean GFP  fluorescence. N=11-13 cells.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "(E) Representative confocal microscopy images of the isogenic HEK293  lines expressing the different GFP-TDP-43 variants for 24 h and stained  for the  Cajal body  marker coilin. Scale bar: 5 µm. (F) Representative  confocal microscopy images of the isogenic HEK293  lines expressing the different GFP-TDP-43 variants for 24 h and hybridized with a fluorescent NEAT1  probe to mark the paraspeckles. Scale bar: 5 µm.",
    "ncbi_link": "GFP: 
NEAT1: 283131
TDP-43: 23435"
  },
  {
    "caption": "(A) Volcano plots showing alternative splicing (AS) events upon expression  of GFP-TDP-43 variants for 48 h.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(E) Western blot  analysis of the isogenic HEK293  after GFP-TDP-43 expression for 48 h showing that only the WT variant regulates endTDP-43  levels. (F) Quantification of the endTDP-43  signal from E. N=4 independent experiments. Two-way ANOVA with Tukey's multiple comparisons post hoc test.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(G) Tripartite GFP  complementation assay involving the co-transfection of a pair of N-terminally T10- and T11-tagged  TDP-43 constructs in HeLa  cells subjected to arsenite  stress for 30 min and incubated with recombinant  GFP1-9 after fixation to label T10- and T11-TDP-43 dimers. TriFC: trimolecular fluorescence complementation. Scale bar: 10 µm. (H) Quantification of the  trimolecular fluorescence complementation  (triFC) signal of GFP  in the TIA-1-marked SGs  from the images shown in G. N=3 independent experiments. Repeated measures one-way ANOVA with Greenhouse-Geisser correction and Tukey's multiple comparisons post hoc test.",
    "ncbi_link": "TDP-43: 23435"
  },
  {
    "caption": "(I) Expression of GFP-TDP-43 mutNLS variants was induced with doxycycline  (DOX) for 4 h before crosslinking protein-protein interactions with DSG  and subsequent analysis by western blot. * and ** indicate GFP-TDP-43 monomers and dimers, respectively. (J) Quantification of the GFP  signal from I. N=3 independent experiments. Repeated measures one-way ANOVA with Greenhouse-Geisser correction and Tukey's multiple comparisons post hoc test.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(K) After expression of GFP-TDP-43 mutNLS variants for 48 h, the isogenic lines were treated with DSG  to cross-link protein-protein interactions  before performing nucleocytoplasmic fractionation and  western blot analysis. * and ** indicate GFP-TDP-43 monomers and dimers, respectively.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(A) Representative  confocal microscopy images of the isogenic GFP-TDP-43  lines after 48 h of expression, treated with the proteasome  inhibitor MG132  for the last 24 h and stained  for lamin B  to mark the nuclear envelope. Note the different localization  of  TDP-43 inclusions in the oligomerization- (6M and 6M&RRMm) versus RNA binding-deficient (RRMm) variants. Scale bar: 20 µm (5 µm for inset). (B) Quantification of the localization  of GFP-TDP-43 inclusions after MG132  treatment for the different variants in the isogenic HEK293  lines as shown in A. Represented values are averages from N=3 independent experiments, with N=189-497 cells quantified per condition and replicate.",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(C) Representative maximum intensity Z-projections from confocal  fluorescence imaging (thickness of 4 µm, in steps of 1 µm) of human neurons  transduced with TDP-43-HA  variants and treated overnight with the proteasome  inhibitor MG132. Scale bar: 10 µm. (D) Quantification of the differentially localized TDP-43-HA  inclusions in human neurons  as described in C. Represented values correspond to the quantification of N=85-97 neurons from two independent experiments. Nuclei  are stained  with DAPI  The neuron-specific marker MAP2  is shown in magenta or cyan",
    "ncbi_link": "HA: 
TDP-43: 23435"
  },
  {
    "caption": "(E) Representative maximum intensity Z-projections from confocal  fluorescence imaging (thickness of 4 µm, in steps of 1 µm) of the same experimental conditions as shown in A, with the addition of a DMSO  control for MG132  treatment. GFP-TDP-43-expressing cells were double immunolabeled  for TDP-43 phosphorylated at the S403/404 and S409/410 epitope. Note the absence of phospho-S409/410 immunopositivity in all conditions and positivity for phospho-S403/404 in cytoplasmic  inclusions and a subset of nuclear GFP-TDP-43  RRMm inclusions (appointed by arrowheads). Scale bar: 10 µm. Nuclei are stained  with DAPI",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(F-G) Representative maximum intensity Z-projections from confocal  fluorescence imaging (thickness of 4 µm, in steps of 1 µm) of the same experimental conditions as shown in C, with the addition of a DMSO  control. TDP-43-HA  expressing human neurons  were stained  for either phospho-S403/404 (F) or phospho-S409/410 (G). Scale bar: 10 µm. Note the re-localization  of the phospho-S403/404 signal from neuronal nuclei  to inclusions (F) and the presence of phospho-S409/410 signal in only a subset of aggregate-bearing neurons  (G). Nuclei  are stained  with DAPI  The neuron-specific marker MAP2  is shown in magenta or cyan",
    "ncbi_link": "HA: 
TDP-43: 23435"
  },
  {
    "caption": "(D) Representative  confocal microscopy  images of the isogenic GFP-TDP-43 lines at the endpoint (24 h) of MG132  treatment of the experimental conditions described in Figure 7A and stained  for vimentin. Scale bar: 5 µm. Cell nuclei are visualized with DAPI",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(E) Representative confocal microscopy images of the isogenic GFP-TDP-43  lines at the endpoint (24 h) of MG132  treatment of the experimental conditions described in Figure 7A and stained  for p62. Cell nuclei  are visualized with DAPI",
    "ncbi_link": "GFP: 
TDP-43: 23435"
  },
  {
    "caption": "(a) PC12 cells stably expressing A53T mutant α-synuclein were induced for 24 h, after which expression was switched off by removing doxycycline from the medium for the next 24 h. Transgene product clearance can be inferred by assessing levels at various times after switching off expression after an initial induction period, as expression levels decay when synthesis is reduced or stopped. Cells were treated with EHNA or AMP-PNP or left untreated during the switch-off period. Blots were probed with antibody to HA to detect the transgene and antibody to actin as a loading control.",
    "ncbi_link": "α-synuclein: 6622"
  },
  {
    "caption": "(b) PC12 cells expressing Q74-GFP were induced for 15 h and then treated with inhibitors for 48 h after switch-off. Band intensity quantification (three independent experiments) is shown.",
    "ncbi_link": "Q74: 3064"
  },
  {
    "caption": "(c) Immunofluorescence images of cells expressing Q74-GFP after 48 h of switch-off after treatment with (EHNA) or without (Control) EHNA.",
    "ncbi_link": "Q74: 3064"
  },
  {
    "caption": "(d) Quantification of aggregates and cell death in COS-7 cells transiently transfected with Q74-GFP either with (EHNA) or without (Control) EHNA (added during the last 33 h before fixation).",
    "ncbi_link": "Q74: 3064"
  },
  {
    "caption": "(e) Western-blot analysis of HeLa cells stably expressing GFP-UbG76V treated with lactacystin (Lac), EHNA or AMP-PNP or left untreated (Control) using antibody to GFP. ***P 0.0001; **P 0.001.",
    "ncbi_link": "Ub: 7316///7314"
  },
  {
    "caption": "(a) Stable PC12 cells expressing A53T α-synuclein were induced for 24 h, after which expression was switched off and cells were simultaneously transfected with p50 or dynamitin (p50), CC1, CC2, motor domain-deleted kinesin heavy chain (ΔM-KHC) or the tail region of kinesin heavy chain (DN-KHC) for the next 24 h. Dominant-negative constructs along with pEGFP-C1 (3:1 ratio of dominant-negative construct:pEGFP-C1) were used to transfect cells, and FACS was used to select transfected cells, which were analyzed by western blotting as in Figure 1a. Quantification of the band intensity from multiple experiments (three independent experiments for dynein mutants and two for kinesin mutants) is shown. ***P 0.0001; *P 0.01; NS, not significant.",
    "ncbi_link": "C1: 
kinesin: 
dynamitin: 10540
p50: 10540
α-synuclein: 6622"
  },
  {
    "caption": "(b) COS-7 cells were cotransfected with HA-Q74 or GFP-Q74 with empty vector (pEGFP or pcDNA3.1), p50 or dynamitin (p50), p62 subunit of dynactin complex (p62), the tail region of kinesin heavy chain (DN-KHC), CC1 or CC2 for 48 h, after which the cells were fixed for immunofluorescence and immunocytochemistry (using to antibody to HA). The percentage of GFP-positive cells with aggregates and cell death is shown. ***P 0.0001; **P 0.001; NS, not significant.",
    "ncbi_link": "kinesin: 
pcDNA3.1: 
dynamitin: 10540
p50: 10540
p62: 51164
Q74: 3064"
  },
  {
    "caption": "(c) Immunocytochemistry analysis (using antibody to HA) of COS-7 cells cotransfected for 48 h with HA-Q74 (red) and pEGFP or p50 (green). Panels on left are magnifications of boxed areas in second panels. The boxes are the same size. ***P 0.0001; **P 0.001. Examples of fragmented nuclei in cells overexpressing p50 and nuclei in cells overexpressing p50 but treated with Z-VAD-fmk (broad-spectrum caspase inhibitor) are shown in Supplementary Figure 4 online.",
    "ncbi_link": "p50: 10540
Q74: 3064"
  },
  {
    "caption": "(a) Immunofluorescence analysis of COS-7 cells cotransfected for 15 h with either empty vector (control) or CC1 and GFP-LC3 (green), in a 3:1 ratio. Panels on right are magnifications of boxed areas.",
    "ncbi_link": "CC1: 1639"
  },
  {
    "caption": "(c) NRK cells transiently transfected for 15 h with either empty vector (control) or CC1 and GFP-LC3 (green), in a 3:1 ratio were immunostained with antibody to lgp120, and the numbers of GFP-LC3 and lgp120 doubly stained vesicles in individual cells were scored.",
    "ncbi_link": "CC1: 1639"
  },
  {
    "caption": "Frequencies of ommatidia with different numbers of rhabdomeres are shown at 3 days after eclosion in progeny of flies expressing mutant huntingtin exon 1 (gmrQ120) crossed to either a control stock (w1118; W) or to Dhc64C (dynein heavy chain mutant; Dhc; a) or Roblk (dynein light chain mutant; Robl; b) flies. P ≤ 0.0001 (Mann-Whitney U test).",
    "ncbi_link": "Dhc64C: 38580
huntingtin: 3064
Robl: 36963"
  },
  {
    "caption": "(c) Ommatidia from the progeny of flies expressing mutant huntingtin exon 1 (Q120) crossed with either control stock (w1118; W) or with Dhc64C (Dhc) flies. All fly experiments were repeated three times independently with similar significance levels. One representative experiment is shown.",
    "ncbi_link": "Dhc64C: 38580
huntingtin: 3064"
  },
  {
    "caption": "(a) Tremor onset and severity in a mouse model of Huntington disease are enhanced by the Loa mutation. At 7 weeks: HdhHD/+ Dnchc1Loa/+ n = 9, HdhHD/+ Dnchc1+/+ n = 9, P = 0.14. At 9 weeks: HdhHD/+ Dnchc1Loa/+ n = 8, HdhHD/+ Dnchc1+/+ n = 9, P = 0.027. At 11 weeks: HdhHD/+ Dnchc1Loa/+ n = 6, HdhHD/+ Dnchc1+/+ n = 9, P = 0.001. At 13 weeks: HdhHD/+ Dnchc1Loa/+ n = 5, HdhHD/+ Dnchc1+/+ n = 8, P = 0.021. At 15 weeks: HdhHD/+ Dnchc1Loa/+ n = 3, HdhHD/+ Dnchc1+/+ n = 5, P = 0.021.",
    "ncbi_link": "Dnchc1: 13424
Hdh: 3064"
  },
  {
    "caption": "(b,c) Dynein mutation reduces motor coordination and muscle function in a mouse model of Huntington disease. HdhHD/+ Dnchc1Loa/+, HdhHD/+ Dnchc1+/+ and Hdh+/+ Dnchc1Loa/+ mice are shown. An average of six mice were used at every time point, with at least three mice per group after 13 weeks. (b) Grip strength. Overall effect for all time points between the three genotypes: P = 0.0024. Overall pair comparison between HdhHD/+ Dnchc1Loa/+ and HdhHD/+ Dnchc1+/+: P = 0.001. Overall pair comparison between HdhHD/+ Dnchc1Loa/+ and Hdh+/+ Dnchc1Loa/+: P = 0.0157. Effect at each time point between the three genotypes: 7 weeks, P = 0.023; 9 weeks, P = 0.001; 11 weeks, P 0.0001; 13 weeks, P = 0.004; 15 weeks, P = 0.336 (most of the double mutants were dead by 15 weeks). (c) Accelerating rotarod. Overall effect for all time points between the three genotypes: P = 0.0367. Overall pair comparison between HdhHD/+ Dnchc1Loa/+ and HdhHD/+ Dnchc1+/+: P = 0.0245. Overall pair comparison between HdhHD/+ Dnchc1Loa/+ and Hdh+/+ Dnchc1Loa/+: P = 0.0553. Effect at each time point between the three genotypes: 8 weeks, P 0.001; 10 weeks, P = 0.005; 12 weeks, P = 0.001; 14 weeks, P = 0.009; 16 weeks, P = 0.039.",
    "ncbi_link": "Hdh: 
Dnchc1: 13424
Hdh: 3064"
  },
  {
    "caption": "(d) Reduced lifespan of HdhHD/+ Dnchc1Loa/+ mice. HdhHD/+ Dnchc1Loa/+ (red line) n = 13, HdhHD/+ Dnchc1+/+ (green line) n = 9, P = 0.038. Mice were subjected to humane end points, and so the survival curve reflects the onset of the end points rather than the complete lifespan. Asterisks (*) represent mice that were found dead without reaching humane end points. No mortality of Hdh+/+ Dnchc1Loa/+ mice was observed.",
    "ncbi_link": "Dnchc1: 13424
Hdh: 3064"
  },
  {
    "caption": "(a) Brain sections from HdhHD/+ Dnchc1+/+ or HdhHD/+ Dnchc1Loa/+ mice were stained with antibody to huntingtin (EM48; green). No EM48-stained aggregates were detected in brains of Hdh+/+ Dnchc1Loa/+ mice. Arrows indicate cells with aggregates.",
    "ncbi_link": "Dnchc1: 13424
Hdh: 3064"
  },
  {
    "caption": "(b) Western-blot analysis of mouse brain lysates from wild-type (WT) or Loa mutant mice using antibodies to LC3 and to actin.",
    "ncbi_link": "Loa: "
  },
  {
    "caption": "Balb/C mice were aerosolically challenged with Rv, Rv∆aosR, and Rv∆aosR::aosR strains. Each data point represents log10 CFU obtained from the infected lung of mice and e­rror bar depicts the median with interquartile range for each group. Each data point represents log10 CFU obtained from the infected spleen of a mice and the error bar depicts the mean with SD for each group.",
    "ncbi_link": "aosR: 886901"
  },
  {
    "caption": "Relative gene expression of selected DEGs measured by qRT-PCR in Rv compared with Rv treated with CHP (g) and Rv as compared with Rv∆aosR under oxidative conditions (h). Data were normalized with respect to 16s rRNA and results are expressed as mean log2 fold change + SD of three independent replicates and is representative of one of two biological replicates.",
    "ncbi_link": "aosR: 886901"
  },
  {
    "caption": "WCLs of Rv, Rv∆aosR, and Rv∆aosR::aosR subjected to 0 or 50 µM of CHP for 6 h were resolved on 15% SDS-PAGE, transferred to nitrocellulose membrane, and probed with indicated antibodies.",
    "ncbi_link": "aosR: 886901"
  },
  {
    "caption": "The promoter of sigA and mec was fused to luciferase, and transformed cells were either left untreated or exposed to CHP stress for 6 h and luciferase activity was measured (mean ±SD; n=6)",
    "ncbi_link": "luciferase: 
mec: 886875
sigA: 887477"
  },
  {
    "caption": "Indicated bacterial strains were subjected to oxidative stress with 50 µM CHP for 6 h and free thiol content was quantified. Data presented is representative of one of two biological replicates, each performed in triplicates (n=3). Y-axis represents µM thiol /µg of WCL (mean ± SD). Metabolite levels of reduced mycothiol, MSH ergothioneine, ERG were measured in Rv, Rv∆aosR, and Rv∆aosR::aosR in normal and CHP stressed cells using LC-MRM MS/MS analysis. The absolute values obtained under normal conditions were normalized to 100% for each strain and the relative values were calculated for samples processed from CHP treated cells. The data indicates relative levels of metabolites (mean percent ± SD) of four replicates (n=4).",
    "ncbi_link": "aosR: 886901"
  },
  {
    "caption": "qRT-PCR measurements for the log2 fold induction (mean ±SD, n=3) for indicated genes in Rv∆aosR and Rv∆aosR treated with 1mM L-cysteine as compared with Rv. All strains were treated with 50 μM CHP. Data were normalized with respect to 16s rRNA and is representative of one of two biological replicates.",
    "ncbi_link": "16s rRNA: 886243
aosR: 886901"
  },
  {
    "caption": "(A) Western blotting analysis confirmed HMCES knockout in 293A cells (293A HMCES KO). Blots also included knockout cells reconstituted with WT SFB- HMCES.",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(B, C) Colony-forming capacity of HMCES KO cells was compared to that of control wild-type 293A cells. (C) Box plot showing colony forming efficiencies of 293A wild-type control and HMCES KO cells. Box limits represent 25th and 75th percentile, centerline shows the median and whiskers extend minimum to maximum. Data include more than three independent repeats performed in duplicates. Student's t-test were performed for statistical analysis (****, p<0.0001). ",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(D) Colonogenic survival assay of 293A wild-type control and HMCES KO cells treated with various concentrations of hydroxyurea (HU) was shown. Seeding density with respect to control was indicated below each image. The images shown are representative of three biological repeats, each performed in duplicate.",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(E) Quantification showing survival fraction of wild-type control (WT) and HMCES KO cells upon HU treatment. Data are presented as mean±s.e.m (n=3, each performed in duplicates) and student's t-test were performed for statistical analysis (ns, not significant; *, p<0.05).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(F) Quantification of colonogenic survival assay upon exposure of WT and HMCES KO cells to ionizing radiation (IR). Data are presented as mean±s.e.m. Quantifications are from three biological repeats performed in duplicates. Student's t-test was performed for statistical analysis (*, p<0.05; **, p<0.01).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(G, H) Sensitivity assay and quantification of surviving WT control and HMCES KO cells determined by colony-forming assay upon exposure to H2O2. Experiments were repeated three independent times, each time performed in duplicates and data are presented as mean±s.e.m. Statistical significance for the corresponding experiment was analyzed by student's t-test (*, p<0.05).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(I) Bar graph showing sensitivity of WT, HMCES KO and stably reconstituted WT cells towards H2O2 treatment. Experiment was repeated two independent times with technical repeats.",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(A, B) Colonogenic assays were performed by adding increasing concentrations of pemetrexed to control wild-type (WT) 293A cells and HMCES knockout (HMCES KO) cells (A) and quantification of results were shown (B). Increasing numbers of cells were seeded with increasing concentrations of the compound to obtain optimal drug-dose response curve. Seeding density with respect to control is indicated below each image. The images shown are representative of three biological repeats, each performed in duplicate. (B) Data are presented as mean±s.e.m. and student's t-test was performed for statistical analysis (****, p<0.0001).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(C) Western blot showing APEX2 levels upon 293A cells infected with viruses encoding scrambled or two independent APEX2 shRNAs.",
    "ncbi_link": "APEX2: 27301"
  },
  {
    "caption": "(D) Colony forming assay was performed to indicate colony forming efficiency in 293A and HMCES KO cells upon infection with viruses encoding scrambled or APEX2 shRNAs.",
    "ncbi_link": "APEX2: 27301
HMCES: 56941"
  },
  {
    "caption": "(E) Sensitivity assay was conducted with WT and HMCES KO cells upon treatment with AP Endonuclease inhibitor III (APEi). Results are presented from two independent experiments and data are presented as mean±s.e.m.",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(F) Colony forming assay was performed with WT and HMCES KO cells upon either pemetrexed treatment alone or in combination with APEi. Data are presented as mean±s.e.m (n=2 each with technical repeats).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(I) Colony formation assay was conducted to reveal proliferation of WT, POLH KD, REV1 KD, HMCES KO, HMCES KO + POLH KD and HMCES KO +REV1 KD cells.",
    "ncbi_link": "HMCES: 56941
POLH: 5429
REV1: 51455"
  },
  {
    "caption": "(J) Representative images showing proliferation of respective shRNA resistant reconstitution of POLH in 293A and HMCES KO cells stably expressing POLH shRNA. Experiment was repeated two independent times in duplicates.",
    "ncbi_link": "HMCES: 56941
POLH: 5429"
  },
  {
    "caption": "(K) Mutagenesis frequency analysis was conducted in 293T scrambled and 293T HMCES shRNA cells using sup F shuttle vector-based assay system. Experiments were repeated three independent times and data are presented as mean±s.e.m. Student's t-test was used to calculate statistical significance (**, p<0.01).",
    "ncbi_link": "HMCES: 56941"
  },
  {
    "caption": "(B) Volcano plot showing DDR CRISPR-CAS9 screen for HMCES KO cells. -log10(p-value) is plotted against log2(HMCES KO/ WT) fold change. Genes showing significant positive and negative enrichment are colored in red and top enriched candidates are also labeled.",
    "ncbi_link": "CAS9: 
CRISPR: 
HMCES: 56941"
  },
  {
    "caption": "Cell proliferation measured using CellTiter-Glo assay in 293A and HMCES KO cells without or with transfection with viruses encoding CtIP (F) shRNAs. Each experiment was repeated three independent times done in triplicates each time. Data was represented as mean±s.e.m. Student's t-test was used to calculate statistical significance (***, p<0.001; ****, p<0.0001).",
    "ncbi_link": "HMCES: 56941
CtIP: 5932"
  },
  {
    "caption": "Cell proliferation measured using CellTiter-Glo assay in 293A and HMCES KO cells without or with transfection with viruses encoding BRCA2 (G) shRNAs. Each experiment was repeated three independent times done in triplicates each time. Data was represented as mean±s.e.m. Student's t-test was used to calculate statistical significance (***, p<0.001; ****, p<0.0001).",
    "ncbi_link": "BRCA2: 675
HMCES: 56941"
  },
  {
    "caption": "A-C Evidence of microglial phagocytosis of photoreceptors in other mouse models of RP. Histological analysis of a rd1mouseretina (A) demonstrates microglial phagocytosis of photoreceptornuclei in vibratome sections (left) and in flat-mounted retina (right). Phagocytosed nuclei were predominantly negative for TUNEL staining (arrows). Similar findings were found in the retinas of the rd16mouse (loss-of-function mutation in the photoreceptor-expressed CEP290 gene, 1 month old) (B) and the RPGRIP-deficient mouse (6 months old) (C). Scale bar, 20 μm.",
    "ncbi_link": "CEP290: 216274
RPGRIP: 77945"
  },
  {
    "caption": "D-G Evidence of microglial phagocytosis of photoreceptors in other human histopathological specimens of RP. (D) Retinal section from a 30-year-old male donor with autosomal recessive RP (AR RP) showing extensive microglial infiltration of the ONL; expanded inset (right) shows multiple photoreceptor nuclei in phagosomes that were predominantly negative for TUNEL staining. (E, F) Retinal sections from two separate donors with autosomal dominant RP (AD RP1 = 68-year-old man, T17M rhodopsin mutation, AD RP1 = 50-year-old woman, Q-64-ter rhodopsin mutation) showing similar evidence of microglial phagocytosis. (G) Retinal section from a 46-year-old male donor with X-linked RP (XL RP). Arrowheads indicate phagocytosed photoreceptor nuclei. Scale bars, 20 μm.",
    "ncbi_link": "rhodopsin: 6010"
  },
  {
    "caption": "Retinalmicroglia were depleted in rd10/CreDTAmice by the oral administration of tamoxifen (in corn oil) to activate microglia-specific Cre-mediated recombination and diphtheria toxin expression; control CreDTA littermates were administered corn oil without tamoxifen.A-D Depletion of retinalmicroglia in the rd10 retina. Representative retinal section from a P28 control animal demonstrates Iba1+microglia in the retina, including those infiltrating the ONL (A), while a tamoxifen-administered littermate (B) was substantially depleted of retinalmicroglia. Scale bar, 40 μm. Microglial cell counts in the entire retina (C) and in the ONL only (D) confirmed efficient depletion of infiltrating microglia following tamoxifen administration (n = 8 control and 11 depleted animals from four litters, two-sided unpaired t-test).E-J Effect of microglial depletion on retinal degeneration at P28-29. ONL atrophy and thinning in control animals (E) was significantly more advanced relative to microglia-depleted littermates (F). Scale bar, 40 μm. Quantification of mean ONL thickness (G) and mean number of layers of ONLnuclei (H) at P28-29 demonstrate significantly greater ONL preservation in depleted retinas; the degree of ONL preservation correlated with the extent of microglia depletion (I). (J) The mean density of TUNEL+nuclei in the ONL was not significantly decreased in depleted vs. control animals (n = 8 control and 11 depleted animals from four litters, two-sided unpaired t-test).K-N Continuation of microglial depletion until P37-39 resulted in the persistence of morphological rescue (K-M), with a significant reduction in TUNEL+nuclei density (N) (n = 6 control and nine depleted animals from two litters, two-sided unpaired t-test).O-R Similar rescue effects as in (K-N) remained apparent when depletion was sustained until P50 (O-R), a time when rod degeneration in the rd10 model is relatively complete (n = 9 control and 10 depleted animals from three litters, two-sided unpaired t-test).S, T Functional rescue of photoreceptors was evident following microglial depletion until P50 in significantly increased dark- (S) and light-adapted (T) responses in ERG testing in depleted animals (green lines) relative to control animals (black lines), in both a- and b-wave amplitudes across multiple flash intensities (n = 9 control and nine depleted animals, *P < 0.05 in one-way ANOVA with Sidak's multiple comparison test).",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "Depletion of infiltrating microglia in the rd10 retina decreases IL-1β levels. Cytokine levels in rd10/CreDTA mouse retinas were assayed following tamoxifen-induced microglial depletion (from P21 to P37-50, green bars; n = 9 animals) and compared with their untreated littermate controls (white bars, n = 8 animals; values normalized to control animals in the same litter). IL-1β protein levels were significantly lowered following microglial depletion, but IL-6, CCL2, or TNFα were not significantly changed.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "Quantification of human EGFL7 by qRT-PCR in primary GBM biopsies and corresponding PDX xenografts upon implantation of GBM-derived organotypic spheroids (n = 3; Mann-Whitney U-test; mean ± SEM); B - GBM biopsy; G - generation.",
    "ncbi_link": "EGFL7: 51162"
  },
  {
    "caption": "Alignment of EGFL7 expression along with stromal (VWF, VEGFR1, VEGFR2, ACTA2, CD248, ITGAX, AIF1, CD68, CD4, and PTPRC) or tumor markers (EGFR, PDGFRA, VEGFA, VIM, and NES) in primary GBM biopsies or GBM-derived organotypic spheroids (PDX xenografts).",
    "ncbi_link": "ACTA2: 59
AIF1: 199
CD248: 57124
CD4: 920
CD68: 968
EGFL7: 51162
EGFR: 1956
VEGFR1: 2321
ITGAX: 3687
VEGFR2: 3791
NES: 10763
PDGFRA: 5156
PTPRC: 5788
VEGFA: 7422
VIM: 7431
VWF: 7450"
  },
  {
    "caption": "Overexpression of human EGFL7 (hE7) or murine EGFL7 (mE7) increased tumor growth (n = 9; one-way ANOVA).",
    "ncbi_link": "EGFL7: 51162
EGFL7: 353156
hE7: 51162
mE7: 353156"
  },
  {
    "caption": "Immunocompetent mice bearing GL261 tumors. Representative MRI images confirmed tumor implantation in all experimental groups (left). Kaplan-Meier curves revealed decreased survival of mice bearing EGFL7 expressing tumors (right; 34 d (control) vs. 29.5 d (hE7) vs. 31.5 d (mE7); n = 8; log-rank test). Immunodeficient mice bearing U87 tumors. Representative magnetic resonance images confirmed tumor implantation in all experimental groups (left). Kaplan-Meier curves revealed decreased survival of mice bearing EGFL7 expressing tumors (right; 70 d (control) vs. 42.5 d (hE7) vs. 40 d (mE7); n = 8; log-rank test).",
    "ncbi_link": "EGFL7: 51162
EGFL7: 353156
hE7: 51162
mE7: 353156"
  },
  {
    "caption": "miR-126 KO did not affect overall survival of GL261 tumor-bearing mice (n = 8).",
    "ncbi_link": "miR-126: 387145"
  },
  {
    "caption": "EGFL7 KO prolonged overall survival of GL261 tumor-bearing mice as compared to wild-type (WT) littermates (44 d in KO vs. 35.5 d in WT; n = 8 each; log-rank test).",
    "ncbi_link": "EGFL7: 353156"
  },
  {
    "caption": "Residual EGFL7 expression in BTPC11 glioma cells was reduced by a lentivirus-based approach. Knock-down of EGFL7 (shE7_1 or shE7_2) prolonged the median survival time of glioma-bearing mice (68 d or 69 d) as compared to scrambled control (shScr; 56 d; n = 6; log-rank test).",
    "ncbi_link": "EGFL7: 51162"
  },
  {
    "caption": "The blood vessel-specific and miR126-independent KO of EGFL7 in EGFL7fl/fl;Cdh5-CreERT2 mice prolonged the overall survival of GL261 tumor-bearing mice as compared to WT littermates (38 d in KO vs. 33 d in WT; n = 7 for KO; n = 5 for WT; log-rank test). All data are presented as mean ± SEM. Scale bars represent 5 mm.",
    "ncbi_link": "Cdh5: 12562
Cre: 2777477
EGFL7: 353156
ERT2: 2099
miR126: 387145"
  },
  {
    "caption": "CD31 staining for endothelial cells revealed increased tumor vascularization in mice bearing human EGFL7 (hE7)- or murine EGFL7 (mE7)-positive tumors (n = 3; one-way ANOVA).",
    "ncbi_link": "EGFL7: 353156
hE7: 51162
mE7: 353156"
  },
  {
    "caption": "T2-weighted magnetic resonance imaging (MRI) analysis of these brains confirmed that all mice developed tumors of similar size. T1-weighted MRI images showed decreased vessel permeability as measured by Gadovist extravasation in tumors expressing hE7 or mE7 (red arrows; n = 6; one-way ANOVA). Scale bar represents 2.5 mm.",
    "ncbi_link": "hE7: 51162
mE7: 353156"
  },
  {
    "caption": "T2-weighted magnetic resonance imaging (MRI) analysis of these brains confirmed that all mice developed tumors of similar size. T1-weighted MRI images showed decreased vessel permeability as measured by Gadovist extravasation in tumors expressing hE7 or mE7 (red arrows; n = 6; one-way ANOVA). Scale bar represents 2.5 mm.",
    "ncbi_link": "hE7: 51162
mE7: 353156"
  },
  {
    "caption": "EGFL7 promoted density and maturation state of glioma vessels Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of PDGFRβ (pericytes) with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "ncbi_link": "EGFL7: 51162
hE7: 51162
mE7: 353156"
  },
  {
    "caption": "Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of SMA (smooth muscle cells), with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "ncbi_link": "hE7: 51162
mE7: 353156"
  },
  {
    "caption": "Enhanced maturation of glioma vessels in the presence of hE7 or mE7 was verified by increased co-localization of (I+J) Col IV (basement membrane) with CD31 (n = 3; one-way ANOVA; quantifications normalized to CD31). Data presented as mean ± SEM, AU-arbitrary units. Scale bars represent 60 µm.",
    "ncbi_link": "hE7: 51162
mE7: 353156"
  },
  {
    "caption": "Ectopic expression of murine EGFL7 (mE7) in GL261 mouse glioma cells followed by intracranial implantation into the striatum of immune-competent mice reduced overall survival but was rescued upon treatment with an integrin α5β1-inhibiting antibody (n = 6; log-rank test). Data presented as mean ± SEM. TCL-total cell lysate, AU-arbitrary units.",
    "ncbi_link": "EGFL7: 353156
mE7: 353156"
  },
  {
    "caption": "Treatment with anti-EGFL7 (47 d), anti-VEGF (51 d), or a combination of both antibodies increased the median survival time of glioma-bearing Rag1-/- mice (58 d) as compared to isotype-treated controls (37 d; n = 6; log-rank test).",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "B) m6A dot blot of Raji cells that expressed NTC or MYC shRNAs (B); equal mRNA loading was verified by methylene blue staining. The shown data are representative of at least three independent experiments.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(C) Quantification of m6A abundance by HPLC-MS. *** P<0.001 as compared to corresponding high MYC group (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(G) m6A-RIP assay in P493-6 cells treated with Tet for 0h or 72h. HPRT1 serves as negative control. *** P<0.001 as compared to corresponding high MYC group, ns, not significant (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "HPRT1: 3251
MYC: 4609"
  },
  {
    "caption": "I) Western blot analysis for protein levels in Raji cells that expressed NTC or MYC shRNAs (I). HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "B) Western blot analysis for protein levels of m6A methyltransferases (METTL3 and METTL14) and demethylases (ALKBH5 and FTO) in Raji cells that expressed NTC or MYC shRNAs (B). β-actin serves as loading controls. Data are representative of at least three independent experiments.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(D) IGV graph showing location of MYC binding peaks on ALKBH5 and FTO from published ChIP-seq datasets (Walz et al, 2014; Data ref: Eilers M, 2014). In this dataset, high levels of MYC were induced with 1µg/ml doxycycline for 30h and ChIPed by MYC antibody. Red triangle indicates the E-box.",
    "ncbi_link": "ALKBH5: 54890
FTO: 79068"
  },
  {
    "caption": "(E) RIP assay, using ALKBH5, FTO or IgG antibody to detect the binding to MRGs (SPI1 and PHF12) in P493-6 cells treated with Tet or not. HPRT1 serves as negative control. *** P<0.001 as compared to corresponding IgG group (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "HPRT1: 3251
PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "(F Western blot analysis for protein levels in P493-6 cells that overexpressed empty vector (EV), ALKBH5, or FTO and were then treated with Tet or not (F) HPRT1 and β-actin served as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "ALKBH5: 54890
FTO: 79068"
  },
  {
    "caption": "G) Western blot analysis for protein levels in Raji cells expressed NTC or MYC shRNAs (G). HPRT1 and β-actin served as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(H) m6A RIP assay in P493-6 cells that overexpressed EV, ALKBH5, or FTO and were then treated with Tet or not. HPRT1 serves as negative control. *** P<0.001 as compared between indicated groups. ns, not significant (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "ALKBH5: 54890
FTO: 79068
HPRT1: 3251"
  },
  {
    "caption": "(I, Western blot analysis for protein levels in P493-6 cells that expressed NTC or ALKBH5 shRNAs and were then treated with Tet or not (I) HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "ALKBH5: 54890"
  },
  {
    "caption": "J) Western blot analysis for protein levels in Raji cells expressed NTC or ALKBH5 shRNAs and knocked down MYC or not (J). HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "ALKBH5: 54890
MYC: 4609"
  },
  {
    "caption": "(K) m6A RIP assay HPRT1 serves as negative control. *** P<0.001 as compared between indicated groups (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "HPRT1: 3251"
  },
  {
    "caption": "(A) RIP assay in P493-6 cells treated with Tet for 0h or 72h. HPRT1 serves as negative control. *** P<0.001 relative to indicating groups (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "HPRT1: 3251"
  },
  {
    "caption": "(B, Western blot analysis for protein levels in P493-6 cells that expressed NTC or YTHDF3 shRNAs and were then treated with Tet or not (B) HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "YTHDF3: 253943"
  },
  {
    "caption": "C) Western blot analysis for protein levels in Raji cells that expressed NTC or YTHDF3 shRNAs and knocked down MYC or not (C). HPRT1 and β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "MYC: 4609
YTHDF3: 253943"
  },
  {
    "caption": "(D) Polysomes profiling assay in P493-6 cells that expressed NTC or YTHDF3 shRNA.",
    "ncbi_link": "YTHDF3: 253943"
  },
  {
    "caption": "(E) RT-qPCR assay for mRNA levels of MRGs (SPI1 and PHF12) in different fractions in (D). HPRT1 serves as negative control. Data were presented as mean (±SD), n = 3 biological replicates. ** P<0.01 and *** P<0.001 as compared to NTC group (Student's t‐test).",
    "ncbi_link": "HPRT1: 3251
PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "(F) Click-iT AHA (L-azidohomoalaine) experiments were performed using IgG, anti-SPI1 or anti-PHF12 antibody. P493-6 cells expressing NTC or YTHDF3 shRNAs were incubated for 1 hour in medium containing 100 ug/mL AHA. The translated proteins were detected by Western blot. Arrow indicates translated MRGs.",
    "ncbi_link": "YTHDF3: 253943"
  },
  {
    "caption": "H) Western blot analysis for protein levels in Raji cells (H) that expressed NTC, or ALKBH5 shRNA, or YTHDF3 shRNA. β-actin serve as negative and loading controls, respectively. Data are representative of at least three independent experiments.",
    "ncbi_link": "ALKBH5: 54890
YTHDF3: 253943"
  },
  {
    "caption": "(I) m6A RIP assay HPRT1 serves as negative control. *** P<0.001 as compared between indicated groups, ns, not significant (mean ± SD, n = 3 biological replicates, Student's t‐test).",
    "ncbi_link": "HPRT1: 3251"
  },
  {
    "caption": "(A) Trypan blue counting was used to analyze growth curves for P493-6 cells that expressed NTC or SPI1 shRNA or PHF12 shRNA. ** P<0.01 as compared between indicated groups. (mean ± SD, n = 4 biological replicates, Student's t‐test)",
    "ncbi_link": "PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "(B, C) Trypan blue counting was used to analyze growth curves for P493-6 cells overexpressing ALKBH5 and further infected with viruses expressing SPI1 (B) or PHF12 (C). ** P<0.01 as compared between indicated groups (mean ± SD, n = 4 biological replicates, Student's t‐test).",
    "ncbi_link": "ALKBH5: 54890
PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "(D, E) Raji cells stably expressing EV or MYC were infected with viruses expressing shALKBH5. Cells were injected subcutaneously into nude mice (n=5 for each group). Tumor growth curves were measured starting from 12 days post injection (D). Photo of tumors collected at the end of the experiment (day 27) (E). Data are presented as mean (±SEM). ** P<0.01 or *** P<0.001 as compared between indicated groups (Student's t‐test).",
    "ncbi_link": "ALKBH5: 54890
MYC: 4609"
  },
  {
    "caption": "(F P493-6 cells stably expressing NTC or shSPI1 or shPHF12 were injected subcutaneously into nude mice (n=5 for each group). Tumor growth curves were measured starting from 12 days post injection (F). Data are presented as mean (±SEM). ** P<0.01 as compared between indicated groups (Student's t‐test).",
    "ncbi_link": "PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "G) P493-6 cells stably expressing NTC or shSPI1 or shPHF12 were injected subcutaneously into nude mice (n=5 for each group). Photo (G) of tumors collected at the end of the experiment (day 25).",
    "ncbi_link": "PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "(H, I) P493-6 cells stably expressing EV or ALKBH5 were infected with viruses expressing SPI1 or PHF12. Cells were injected subcutaneously into nude mice (n=5 for each group). Tumor growth curves were measured starting from 17 days post injection (H). Photo (I) of tumors collected at the end of the experiment (day 32). Data are presented as mean (±SEM). * P<0.05 as compared between indicated groups (Student's t‐test).",
    "ncbi_link": "ALKBH5: 54890
PHF12: 57649
SPI1: 6688"
  },
  {
    "caption": "A. Trem2  CV and Trem2  R47H KI primary microglia treated simultaneously with oAβ-bound synaptosomes  (SN) conjugated with pHrodo red  (magenta) and control SN, conjugated with pHrodo deep red (cyan). Scale bar, 50 μm. B. pHrodo  fluorescence with time shown as AUC at 3 h. AUC of oAβ-SN  is higher compared to Ctrl-SN  in Trem2  CV but not in Trem2  R47H KI microglia. ∼40 microglia  per ROI, 2 ROIs per well, 2-3 wells per experiment, n=3 independent experiments. C. Quantification of the percent of C1qa  area covered normalized to WT showing an increase in the  NL-F but not NL-F KI; Trem2  R47H KI. N=3-4 animals per genotype. Data information: Data shown as mean ± SEM. Each shaded point represents 1 ROI, and each open point represents the mean of each independent experiment. Two-way ANOVA followed by Bonferroni's post-hoc test. P-values shown as ns P>0.05; *P<0.05; ***P<0.001; ****P<0.0001.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "Hippocampal CA1 SR  of 6 mo WT, Trem2  R47H KI, NL-F KI and NL-F KI; Trem2  R47H KI mice immunostained  for P2Y12  (red), CD68  (magenta) and Homer1 (green). G. Representative 3D surface rendering reconstructions showing increased Homer1  in microglia  in NL-F KI compared to WT, Trem2 R47H KI, and NL-F KI; Trem2  R47H KI mice. Scale bar, 10 μm.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "I. SRM  images from the hippocampal CA1 SR   of 6 mo WT, Trem2  R47H KI, NL-F KI and NL-F KI; Trem2  R47H KI mice immunostained  for Synaptotagmin (Syt1/2, magenta) and Homer1  (green), pre- and  post-synaptic   puncta, respectively. Scale bar, 1 μm.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "B. Percentage of synaptic Homer1-immunoreactive puncta found  co-localized  with PSVue  in NL-F KI; Trem2  R47H compared to NL-F KI. 3 ROIs per animal, n=3-4 animals per genotype. Data information: Data shown as mean ± SEM. Unpaired t-test (B) P-values shown as ns P>0.05; *P<0.05; **P<0.01, ****P<0.0001.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "D. Number of spontaneous calcium  transients per minute at 48 h post-treatment of Aβ  oligomer in neuron-only culture (cyan), neuron- Trem2  CV microglia  co-culture (magenta) or neuron- Trem2  R47H KI microglia  co-culture (purple). ∼10 spines  per neuron, ∼10 neurons  per experiment, from 3-4 independent experiments. Data information: Data shown as mean ± SEM. Each shaded point represents 1 ROI, and each open point represents the mean (or median for GCaMP  studies) of each independent experiment. Central bands of the violin plot (D) represent median and quartiles. Kruskal-Wallis test followed by Dunn's test (D), P-values shown as ns P>0.05; *P<0.05; **P<0.01, ****P<0.0001.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "F. SRM  3D images from the  hippocampal CA1 SR of 6 mo WT, Trem2  R47H KI, NL-F KI and NL-F KI; Trem2  R47H KI mice immunostained  for Bassoon  (cyan), a presynaptic  marker enriched in functional  active zones. Scale bar, 1 μm.",
    "ncbi_link": "Trem2: 83433"
  },
  {
    "caption": "G. Representative  western blots  comparing levels of cleaved  caspase-3 (17/19 kDa) and procaspase-3  (35 kDa) with respect to GAPDH  (38 kDa) loading control in synaptosomes  isolated from human  NDC, AD, NDC TREM2  and AD TREM2 brains. 1 lane represents 1 patient.",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "H. Western blot densitometry  analysis showing cleaved caspase-3 levels (left graph) and the ratio of cleaved caspase-3/procaspase-3 (right graph) in synaptosomes  (SN) isolated from human  NDC, AD, TREM2  NDC and TREM2  variants. N= 9 NDC, 11 AD, 5 TREM2  NDC, 10 TREM2 AD  cases. Data information: Data shown as mean ± SEM. The top and the bottom of the box plot (H) represent the 75th and 25th percentiles, respectively, and the line represents the median. The whiskers represent the highest and lowest values that are not outliers. One-way (H) ANOVA followed by Bonferroni's post-hoc test. P-values shown as ns P>0.05; *P<0.05; **P<0.01, ****P<0.0001.",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "(C) Quantitative RT-PCR analysis of mRNA encoding CD1d in freshly isolated ILC3s (from mLN of CD1d-deficient mice and mLN and spleen of WT mice), B cells and DCs (n=3). Results are normalized to those of GAPDH; RE=relative expression. **p< 0.01 (two-tailed unpaired t-test).",
    "ncbi_link": "GAPDH: 
CD1d: 12480///12479"
  },
  {
    "caption": "(D-F) Sort-purified ILC3s were preincubated with αGalCer (ILC3(αGal)) or PBS (ILC3(cont)) and adoptively transferred into WT recipients. (E) Fold change in mRNA expression for the indicated cytokines in iNKT cells sort-purified from spleen, mLN or SI-LP of mice injected with αGalCer-loaded ILC3s. Gene expression was measured by qPCR, normalized to GAPDH and presented as expression relative to iNKT cells sort-purified from mice injected with control ILC3s (n=3-5).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "(A-B) Flow-cytometry plots showing gating strategy (A) and percentage of ILC populations (from Lin-CD45+CD127+cells, B) in mLN from WT (n=4) and CD1d-deficient (n=3) mice.",
    "ncbi_link": "CD1d: 12480///12479"
  },
  {
    "caption": "(A-B) Flow-cytometry plots showing gating strategy (A) and percentage of ILC populations (from Lin-CD45+CD127+cells, B) in mLN from WT (n=4) and CD1d-deficient (n=3) mice.",
    "ncbi_link": "CD1d: 12480///12479"
  },
  {
    "caption": "(C) Fold change in mRNA expression for the indicated cytokines in ILC3s after antibody-mediated CD1d crosslink (n=3). Gene expression was measured by qPCR and normalized to GAPDH and to the mRNA expression levels in control ILC3s. *p<0.05 two-tailed unpaired t-test.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "(D) Fold change in IL22 mRNA expression in ILC3s after antibody-mediated CD1d crosslink and/or IL-23 stimulation (n=4). Gene expression was measured by qPCR and normalized to GAPDH and to the mRNA expression levels in control ILC3s. **p<0.01 two-tailed unpaired t-test.",
    "ncbi_link": "GAPDH: 
IL22: 50929"
  },
  {
    "caption": "(I-J) Fold change in mRNA expression for the indicated cytokines in ILC3s sort-purified from spleen (I) or SI-LP (J) 6 h after intravenous (I) or oral (J) αGalcer administration. Gene expression was measured by qPCR and normalized to GAPDH and to the expression levels in ILC3s sort-purified from PBS-injected mice (n=3). *p<0.05, **p<0.01 two-tailed unpaired t-test.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "A Immunoblot of CCNL1 and FBXW7 expression in HPAF-II wild-type and FBXW7-/- cells, representative blot of 3 independent replicates.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "B Immunoblot of CCNL1 expression following a cycloheximide chase in HPAF-II wild-type and FBXW7-/- cells , representative blot of 3 independent replicates. C Quantification of cycloheximide chase in B, mean ± SEM of three independent replicates.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "D Immunoblot of CCNL1 expression in HPAF-II wild-type and dN-Cul1 expressing cells, representative blot of 3 independent replicates.",
    "ncbi_link": "Cul1: 8454"
  },
  {
    "caption": "G Immunoblot of lysates following cycloheximide treatment of HEK293T cells expressing wild-type or degron-mutated CCNL1, representative blot of 3 independent replicates. H Quantification of cycloheximide chase in G, mean ± SEM of three independent replicates.",
    "ncbi_link": "CCNL1: 57018"
  },
  {
    "caption": "A Immunoblot of immunoprecipitation of FLAG-FBXW7 overexpressed in HEK293T cells, detecting endogenous CCNL1. Representative of three independent replicates.",
    "ncbi_link": "FLAG: 
FBXW7: 55294"
  },
  {
    "caption": "B Immunoblot of immunoprecipitation of FLAG-CCNL1 overexpressed in HEK293T cells, detecting endogenous FBXW7. Representative of three independent replicates.",
    "ncbi_link": "FLAG: 
CCNL1: 57018"
  },
  {
    "caption": "D Immunoblot of cellular ubiquitination assay demonstrating the requirement of FBXW7 for ubiquitination of CCNL1. Representative of three independent replicates.",
    "ncbi_link": "CCNL1: 57018
FBXW7: 55294"
  },
  {
    "caption": "E Immunoblot of cellular ubiquitination assay showing re-expression of FBXW7 in knockout cells leads to increased CCNL1 ubiquitination. Representative of three independent replicates.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "B Immunoblot of HPAF-II wild-type and FBXW7-/- released from overnight nocodazole treatment at indicated time points,",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "D Representative images of GFP-tubulin labeled wild-type, FBXW7-/-, and CCNL1OE HPAF-II cells monitoring cellular progression through cytokinesis following arrest in prometaphase using monastrol (150μM for 18 hours). E Quantification of cytokinetic timing, n=20, 25, 26 (wild-type, FBXW7-/, CCNL1OE ) pooled from three independent experiments F Immunoblot of wild-type, FBXW7-/- and CCNL1OE HPAF-II cell lines demonstrating varying levels of CCNL1.",
    "ncbi_link": "CCNL1: 57018
FBXW7: 55294"
  },
  {
    "caption": "A Clonogenic growth assays for HPAF-II wild-type and FBXW7-/- polyclonal, and FBXW7-/- clones in presence of various OTS964 doses for 14 days. Representative images of 4 independent replicates, quantified by crystal violet absorbance at A595 and B Clonogenic growth assays for HPAF-II wild-type and CCNL1OE polyclonal, and CCNL1OE clones in presence of various doses of OTS964 for 14 days. Representative images of 4 independent replicates, quantified by crystal violet absorbance at A595",
    "ncbi_link": "CCNL1: 57018
FBXW7: 55294"
  },
  {
    "caption": "C Immunoblot for the indicated proteins from lysates extracted from the individual FBXW7-/- and CCNL1OE clones.",
    "ncbi_link": "CCNL1: 57018
FBXW7: 55294"
  },
  {
    "caption": "B Immunoblot of lysates from cervical cell lines demonstrating C33A cells (FBXW7R465H) express high levels of CCNL1, representative of three independent replicates.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "B Average seizure score of KA-treated WT and Fxr2 KO mice over time from t=0 (injection time) to 2 h. * p < 0.05 compared to WT mice (two-way Repeated Measures ANOVA; interaction effect of time and genotype; F1,666 = 10.05, p = 0.0016). KA-treated WT mice (n=16), KA-treated Fxr2 KO mice (n=12). Data are presented as mean ± Standard Error of the Mean (SEM). D Average seizure score of pilocarpine-treated WT and Fxr2 KO mice over time from t=0 (injection time) to 2 h (two-way Repeated Measures ANOVA). Pilocarpine-treated WT mice (n=6), pilocarpine-treated Fxr2 KO mice (n=6). Data are presented as mean ± SEM.",
    "ncbi_link": "Fxr2: 23879"
  },
  {
    "caption": "B PSD-95 mRNA had lower read counts in Fxr2 KO samples (n=3) compared to WT samples (n=3) (+ adjusted p < 0.1, two-tailed Student's t-test). Data are presented as mean ± SEM.",
    "ncbi_link": "PSD-95: 13385
Fxr2: 23879"
  },
  {
    "caption": "A Representative Western blot and quantification of GluK5, PSD-95, GluN2B and mGluR5 proteins. Endogenous GluK5, PSD-95, GluN2B and mGluR5 in Fxr2 KO mice (n=9) compared to WT mice (n=11). * p < 0.05, ** p < 0.01, significant difference between WT and Fxr2 KO (two-tailed Student's t-test: GluK5: t18 = 0.87, p = 0.394; PSD-95: t18 = 2.29, p < 0.05; GluN2B: t18 = 3.09, p < 0.01; mGluR5: t18 = 3.74, p < 0.01). Quantified bands are highlighted with an asterisk or squared bracket. Data are presented as mean ± SEM.",
    "ncbi_link": "Fxr2: 23879"
  },
  {
    "caption": "A Bar plot showing phospho-ERK1/2 over total ERK1/2 levels in vehicle- and KA-treated WT (closed and open black circles, vehicle-treated WT n=6; KA-treated WT n=6) and Fxr2 KO mice (closed and open magenta circles, vehicle-treated Fxr2 KO n=5; KA-treated Fxr2 KO n=6). *** p < 0.001 comparison between vehicle- and KA-treated WT (two-way ANOVA: interaction effect between genotype and treatment: F1,19 = 24.66, p < 0.001). Data are presented as mean ± SEM. B Phospho-ERK1/2 levels in vehicle- and pilocarpine-treated WT (n=4-6) and Fxr2 KO mice (n=4-6). Both genotypes responded with long-lasting seizures upon pilocarpine administration * p < 0.05 (two-way ANOVA: main effect for treatment: F1,16 = 10.98, p < 0.01). Data are presented as mean ± SEM. ",
    "ncbi_link": "Fxr2: 23879"
  },
  {
    "caption": "D Effect of forced SAC  activation. Oocytes  expressing MAD1-mNeonGreen-CENP-C (green), together with major satellite-mClover  (green) and H2B-mCherry (red), were imaged. Time  after the start of imaging   (h:mm) is shown. Oocytes were categorized based on anaphase  figures (n = 24, 23 oocytes).",
    "ncbi_link": "mNeonGreen: 
CENP-C: 12617
MAD1: 17120"
  },
  {
    "caption": "D. Subcellular localization  of BES1-CFP in  roots  of 7-day-old plants after  heat shock. 35S:BES1-CFP seedlings were grown at 21°C and either left untreated or exposed for 60 minutes to 45°C. Left: representative photos. Right: quantification of the nuclear/cytoplasmic signal. Data show the mean ±SD. n=25. The asterisks indicate significant differences to the untreated plants by Student's t-test (***P≤0.001).",
    "ncbi_link": "CFP: 
BES1: 838518"
  },
  {
    "caption": "F. Heat stress resistance of bes1-1, bes1-2 and  bes1-D as compared to wild-type. For basal resistance assays (top charts) plants were directly exposed to 45°C for the indicated  time. For acquired resistance (bottom charts), plants  were primed with the respective temperatures for 120 minutes before transfer to 45°C for 150 minutes. Data show the mean ±SE. n=7. The asterisks indicate significant differences compared to wild-type by Student's t-test (*P≤0.05; **P≤0.01; ***P≤0.001).",
    "ncbi_link": "bes1: 838518"
  },
  {
    "caption": "B.  Immunodetection of BES1-CFP from heat-stressed plants, treated with epiBL or BRZ. 35S:BES1-CFP plants were treated for 24 hours with  DMSO (control), 1 μM 24-epiBL or 5 μM  BRZ  and then heat-stressed as follows: lane 1: untreated control; lane 2: 45°C for 30 minutes; lane 3: 45°C for 60 minutes; lane 4: 45°C for 60 minutes and recovery at 21°C for 180 minutes.",
    "ncbi_link": "CFP: 
BES1: 838518"
  },
  {
    "caption": "C, D.  Immunodetection  of BES1-CFP  from heat-treated bri1-1 or det2-1 plants. Left: phenotypes of 10-day-old  plants of all lines as compared to wild-type  Col-0 (wt). Right: Immunoblots  from the lines grown and treated as in B.",
    "ncbi_link": "bri1: 830095
det2: 818383"
  },
  {
    "caption": "F. Immunodetection  of  BES1-CFP  from  heat-treated  bin2-1 plants.",
    "ncbi_link": "bin2: 827605"
  },
  {
    "caption": "A.  Immunodetection of BES1-CFP from  heat-stressed plants, treated with ABA or Fluridone (Flu). 35S:BES1-CFP plants were treated for 24 hours with DMSO (control), 5 μM ABA or 10 μM  Fluridone and heat-stressed  as follows: lane 1: untreated control; lane 2: 45°C for 30 minutes; lane 3: 45°C for 60 minutes. The non-phosphorylated BES1 bands were quantified with ImageJ and the obtained values are shown in blue.",
    "ncbi_link": "CFP: 
BES1: 838518"
  },
  {
    "caption": "C. Immunodetection of native  BES1 from heat-stressed and epiBL-treated abitM plants. abitM and wild-type plants were grown on ½ MS medium either containing  DMSO as a control or 1 μM epiBL and either left untreated or exposed to 45°C for 60 minutes. The non-phosphorylated BES1 bands were quantified with ImageJ and the obtained values are shown in blue.",
    "ncbi_link": "abi: 828714"
  },
  {
    "caption": "C. ChIP to determine BES1-CFP enrichment on the promoters of HSP70.3, HSP70.4  and HSP90.1 following heat stress. 35S:BES1-CFP and wild-type  plants grown at 21°C were either left untreated or treated with 45°C for 60 minutes. BES1-CFP  was immuno-precipitated  with α-GFP beads. Fragments were quantified in the precipitates with  qPCR and the ratios of samples with antibody to without antibody were calculated. TA3 (70.3p and 90.1p) or 5s rRNA (70.4p) were used for normalization. UBQ5 served as an internal control. Data show the mean ±SE. n=3 biological replicates measured in 3 technical repeats. Significant differences as compared to wild-type at 21°C, calculated by Student's t-test, are shown (*P≤0.05; **P≤0.01; ***P≤0.001).",
    "ncbi_link": "5s rRNA: 
CFP: 
TA3: 
HSP70.3: 820102
BES1: 838518
HSP70.4: 820438
HSP90.1: 835341
UBQ5: 825398"
  },
  {
    "caption": "A. EMSAs showing in vitro DNA  interaction of recombinant  BES1  and/or  HSFA1 with HSE-containing fragments of the  HSP70.3  and  HSP90.1 promoters. Unlabeled competitor fragments with functional  HSEs (C1 +HSE) or mutated versions (C2 -HSE) were used for competition studies in 100x molar access (lanes 6 and 7).",
    "ncbi_link": "HSP70.3: 820102
HSP90.1: 835341"
  },
  {
    "caption": "C.  LUC assays in protoplasts  of wild-type, bes1-D or the hsfA1qM plants. LUC  reporter constructs, driven by 2 kb of the HSP70.3, HSP70.4 and HSP90.1 promoters, were tested either alone (0, with empty effector plasmid) or with  BES1 or HSFA1a  as effectors and LUC  transactivation was analyzed. Data show the mean ±SD. n=5. Statistically significant difference at P≤0.05 of results is indicated with different letters and was determined by Student's t-test.",
    "ncbi_link": "LUC: 
HSP70.3: 820102
bes1: 838518
BES1: 838518
hsfA1: 827496
HSFA1a: 827496
HSP70.4: 820438
HSP90.1: 835341"
  },
  {
    "caption": "A, B. Constitutive and BR-responsive  growth  of bes1-DxhsfA1qM seedlings. Hypocotyl  elongation of 7-day-old dark-grown (A) and light-grown (B)  seedlings on medium containing either 1 μM  epi-BL, 1 μM  BRZ or DMSO as a control (c). Left: Mean and SD of 30 plants. Significant difference at P≤0.05 of results is indicated with different letters and was determined with a Student's t-test. Right: photos of representative plants.",
    "ncbi_link": "bes1: 838518
hsfA1: 827496"
  },
  {
    "caption": "C. Expression of BR-regulated genes in bes1-DxhsfA1qM, as compared to its parents and respective wild-types analyzed by  qPCRs. Data show the mean ±SD. n=3 biological repeats, each measured in 3 technical replicates, normalized to  UBC. Statistically significant difference at P≤0.05 of results is indicated with different letters and was determined by Student's t-test.",
    "ncbi_link": "bes1: 838518
hsfA1: 827496"
  },
  {
    "caption": "B Representative images of Drosophila adult wings that resulted from larvae wing imaginal discs expressing a control RNAi (mCherry RNAi), a lds RNAi, or co-expressing san RNAi with control RNAi (san RNAi control RNAi) or with lds RNAi (san RNAi lds RNAi).",
    "ncbi_link": "mCherry: 
lds: 45894
san: 44724"
  },
  {
    "caption": "A Representative images of cells in the wing disc pouch upon nub-Gal4-mediated RNAi for lds (bottom) compared to a nub-Gal4 control (top). Cells also express HisH2AvD-mRFP1 (magenta) and centromeric marker cid-EGFP (green); Times (min:sec) are relative to NEBD; scale bars 5 µm and applies to all images. B Mitotic timing defined from NEBD to anaphase onset; each dot represents a different cell (n=77 cells from at least 6 independent movies per condition); black lines represent mean; statistical analysis was performed using the non-parametric Mann-Whitney test. Data information: Scale bars are 10 µm and apply to all images.",
    "ncbi_link": "Gal4: 855828
lds: 45894
nub: 34669"
  },
  {
    "caption": "A Analysis of ongoing transcription monitored by MCP-EGFP labelled nascent transcripts on a reporter containing MS2 loops (green), in the referred experimental conditions. Flies also express H2AvD-mRFP1 (magenta). Scale bar is 10 µm and applies to all images.",
    "ncbi_link": "EGFP: 
MCP: 
mRFP1: 
MS2: 
H2AvD: 43229"
  },
  {
    "caption": "B Segregation defects upon inhibition of transcription in luciferase and lds RNAi. Graph depicts mean ± s.e.m. of the frequencies of defects scored in 11 (luciferase RNAi, H2O and lds RNAi, α-amanitin) or 8 (lds RNAi, H2O and Luc RNAi, α-amanitin) independent embryos; a total of ~800 nuclei were scored per condition.",
    "ncbi_link": "Luc: 
luciferase: 
lds: 45894"
  },
  {
    "caption": "A Wing morphology phenotype obtained upon depletion of Lds combined with control co-depletion (luciferase RNAi) or expression/depletion of chromosome architecture modulators. Wing morphology defects were classified according to their severity (1= normal wings and 5= no wing); depicted numbers indicate the average morphology grade and the number of flies counted, from at least 2 independent experiments.",
    "ncbi_link": "luciferase: 
Lds: 45894"
  },
  {
    "caption": "B Live cell imaging analysis of the kinetics of Rad21-EGFP (green) removal from mitotic chromosomes in luciferase- and lds-depleted embryos. DNA is marked with H2AvD-mRFP1 (magenta); times are relative to NEBD; scale bar is 10 µm and applies to all images.",
    "ncbi_link": "luciferase: 
lds: 45894"
  },
  {
    "caption": "(A, Chromatin localisation of chromosome assembly factors (Top2 (A) in green) upon RNAi for luciferase (left) or lds (right) in early embryos. DNA is marked with H2AvD-mRFP1 (magenta); scale bars are 10 µm and apply to all images.",
    "ncbi_link": "luciferase: 
lds: 45894"
  },
  {
    "caption": "C) Chromatin localisation of Condensin I subunit Barren (C), in green) upon RNAi for luciferase (left) or lds (right) in early embryos. DNA is marked with H2AvD-mRFP1 (magenta); scale bars are 10 µm and apply to all images.",
    "ncbi_link": "luciferase: 
lds: 45894"
  },
  {
    "caption": "G Telophase images of embryos depleted for luciferase (left), Cap-D2 (middle) and wapl (right) RNAi, and expressing Lds-EGFP (green) and HisH2AvDmRFP1 (magenta). Bottom panels depict Lds-EGFP alone. Scale bar is 10 µm and applies to all images.",
    "ncbi_link": "luciferase: 
Cap-D2: 43491
wapl: 31187"
  },
  {
    "caption": "A, Representative images of mitotic nuclei in prophase (1 min before NEBD) and metaphase (1 min before anaphase onset), upon RNAi for luciferase/lds, microinjected with water (A) Scale bars are 5 µm and refer to all images.",
    "ncbi_link": "luciferase: 
lds: 45894"
  },
  {
    "caption": "B Representative images of mitotic nuclei in prophase (1 min before NEBD) and metaphase (1 min before anaphase onset), upon RNAi for luciferase/lds ICRF-193 (B). Scale bars are 5 µm and refer to all images.",
    "ncbi_link": "luciferase: 
lds: 45894"
  },
  {
    "caption": "(B) Representative kymographs and quantification of anterograde, retrograde, mean velocity, and linear flow rate of BDNF-mCherry-containing vesicles in cortical neurons transfected with siMecp2 (n= 753 vesicles/ 81 axons) or siControl (siCtl) (n= 894 vesicles/ 94 axons), inducing significant silencing of Mecp2 (3 independent experiments; unpaired t-test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 Data are presented as the means ± SEM.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "(C) Quantification of anterograde, retrograde, mean velocity, and linear flow rate of BDNF-mCherry trafficking into cortical neurons obtained from WT (n= 753 vesicles/ 81 axons), HTTSA (n= 812 vesicles/ 81 axons), or HTTSD (n= 787 vesicles/ 82 axons) homozygous knock-in mice in which S421 of HTT was replaced by an alanine (HTTS421A/S421A or HTTSA), mimicking the absence of phosphorylation, or by an aspartic acid (HTTS421D/S421D or HTTSD), mimicking constitutive phosphorylation (3 independent experiments; one-way ANOVA test with Tukey's multiple comparisons). Data information: , ***p < 0.001, ****p < 0.0001, ns = not significant. Data are presented as the means ± SEM.",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "(D) Cell viability in WT (n=3), HTTSA (n=1), or HTTSD (n=2) neurons measured by MTT assay. No differences were observed between the different groups (3 independent experiments; one-way ANOVA Kruskal-Wallis test, p=0.5701 Data information: ns = not significant. Data are presented as the means ± SEM.",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "(E) Kymographs and quantification of anterograde, retrograde, mean velocity, and linear flow rate of BDNF-mCherry axonal trafficking into WT (n= 894 vesicles/ 94 axons), HTTSA (n= 812 vesicles/ 82 axons), or HTTSD (n=787 vesicles/ 94 axons) cortical neurons transfected with siCtl or siMecp2, which significantly silenced Mecp2 (3 independent experiments; one-way ANOVA with Tukey's multiple comparisons). (F) Cell viability in WT, HTTSA, or HTTSD neurons transfected with siCtl or siMecp2 measured by MTT assay (WT siCtl: n=3; WT siMecp2: n=3; HTTSD siMecp2: n=3; HTTSA siMecp2: n=2). No differences were observed between the different groups (3 independent experiments; one-way ANOVA Kruskal-Wallis test, p=0.5701) Data information: Scale bars = 20 µm. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant. Data are presented as the means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "(A) Left: The ratio between the striatal and the cortical BDNF determined by quantifying the level of BDNF proteins at the cortex and the striatum of 55 day-old WT (n=8), Mecp2 KO (n=6), Mecp2 KO/HTTSD (mimicking the absence of phosphorylation) (n=4) and Mecp2 KO/HTTSA mice (mimicking constitutive phosphorylation) (n=5). Since striatal BDNF depends only on BDNF transport from the cortex, this ratio reflects BDNF transport through corticostriatal pathway (Mann Whitney test). Right: Quantitative analysis of phospho TrkB protein level in striatum of KO WT mice and KO HTTSD mice by immunoblotting. The relative expression levels of phospho TrkB were normalized against GAPDH and are presented as the ratio. (n = 6 mice per group) (Mann Whitney test) Middle: Quantitative analysis of PSD-95 protein level in striatum of Mecp2 KO/HTT WT mice and KO/HTTSD mice by immunoblotting. The relative expression levels of PSD-95 were normalized against GAPDH and are presented as the ratio. (n = 6 mice per group) (Mann Whitney test) Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "(B) Left: We investigated the behavior of Mecp2 KO mice at 35, 45, and 55 days of age and assessed their survival. Right: Mecp2 KO/HTTSD mice (n = 30) and WT mice (n = 17) had a significantly longer lifespan than KO (n=22) or KO/HTTSA mice (n = 21) (Kaplan-Meier survival test). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "(C) Body weight of 10 WT, 24 KO, 32 KO/HTTSD, and 24 KO/HTTSA mice at P30 and P50 (one-way ANOVA with Tukey's comparison). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "(D) Frequency of apnea of 9 WT, 10 KO, 14 KO/HTTSD, and 9 KO/HTTSA mice at P35 and P55. (Kruskal-Wallis test with Dunn's comparison). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "(E) Mecp2 KO/HTTSD mice (n=19) performed as well as WT (n=17) at P35 on the accelerating rotarod test and continued to outperform Mecp2 KO (n=16) and Mecp2 KO/ HTTSA (n=13) at P55 (one-way ANOVA with Fisher's LSD test). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "(F) Time before the onset of spontaneous locomotor activity of 17 WT, 20 KO, 19 KO/HTTSD, and 17 KO/HTTSA mice at P55. (Kruskal-Wallis test with Dunn's comparison). Data information: Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 ns = not significant.",
    "ncbi_link": "HTT: 15194"
  },
  {
    "caption": "(A) Western blot analysis of DIV 5 cortical neurons transfected with siMecp2 or siControl (siCtl) and treated with 1 µM FK506 or vehicle for 1 h, and quantification of pS421 HTT (n=9 per group). Data are presented as means ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, Mann-Whitney test.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "(B) Representative kymographs showing axonal trafficking of BDNF-mCherry-containing vesicles in cortical neurons transfected with siMecp2 or siControl (siCtl) and treated with 1 µM FK506 or vehicle for 1 h. Scale bar = 20 µm.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "(C) Quantification of anterograde, retrograde, mean velocity, linear flow rate and number of BDNF-mCherry-containing vesicles from the data in (A) (siMecp2+Vehicle: n=801 vesicles/95 axons; siMecp2+FK506: n=1020 vesicles/116 axons; siCtl+Vehicle: n=780 vesicles/83 axons; siCtl+FK506: n=1029 vesicles/102 axons). Data are presented as the mean ± SEM of at least three independent experiments (one-way ANOVA with Tukey's comparison). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "(A) Western blot of HTT S421 phosphorylation. We treated 30-day-old Mecp2 KO mice intraperitoneally with FK506 (5 mg/kg) or vehicle and analyzed brain extracts for endogenous HTT phosphorylation by western blotting, 2 h after administration, using an anti-phospho-HTT-S421 specific antibody. The D7F7 antibody recognizes total HTT. The relative protein level of phospho HTT was normalized on total HTT protein level and are presented as the ratio (KO FK506 n = 4, KO Vehicle n = 4). Data are presented as means ± SEM, *p < 0.05, Mann Whitney test.)",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (B) FK506-treated KO mice lived longer than vehicle-treated KO mice and FK506-treated KO HTTSA mice (Kaplan-Meier survival test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (C) Body weight of FK506-treated KO, FK506-treated KO HTTSA and vehicle-treated KO mice at P35 and P55 (Mann-Whitney test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (D) Frequency of apnea of FK506-treated KO, FK506-treated KO HTTSA and vehicle-treated KO mice at P35 and P55 (Mann-Whitney test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (E) Motor coordination of FK506-treated KO, FK506-treated KO HTTSA and vehicle-treated KO mice on the accelerating rotarod test at P30 and P50 (Mann-Whitney test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "We treated 30-day-old Mecp2 KO mice (n=10) and Mecp2 KO/HTTSA mice (n=10) with 5mg/kg FK506 three times a week by intraperitoneal injection and assessed them in various behavioral tests. (F) Forelimb strength of FK506-treated KO, FK506-treated KO HTTSA and vehicle-treated KO mice assessed by the grip strength test at P40 and P60 (Mann-Whitney test). Data information: *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "HTT: 15194
Mecp2: 17257"
  },
  {
    "caption": "(A) Phenotype appearance of the Gmlmm1-1 mutant. Typical leaves (left panel; scale bar, 1 cm) and whole plants (right panel; scale bar, 10 cm.) were photographed 60 and 118 days after seeding, respectively. Data information: The experiments were performed three times as biological replicates, with similar results.",
    "ncbi_link": "Gmlmm1: 100499640"
  },
  {
    "caption": "(B) Enhanced resistance of Gmlmm1-1 and Gmlmm1-2 to Psg infection. Leaves from 2-week-old soybean plants were infected with Psg and the bacteria number was determined at 0 and 4 dpi (Mean ± SD, n = 8, n represents sample number, ***, p < 0.001, Student's t-test). Data information: The experiments were performed three times , as biological replicates, with similar results.",
    "ncbi_link": "Gmlmm1: 100499640"
  },
  {
    "caption": "(E) Subcellular localization of GmLMM1-GFP and GmLMM1L407H-GFP in N. benthamiana. PI4P indicates the membrane localization. Scale bar, 10 μm. GFP, green fluorescent protein. Data information: The experiments were performed three times as biological replicates, with similar results.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": "(A) ROS accumulation in Gmlmm1-1 and Gmlmm1-2 mutant plants. Soybean leaves (aged 3 weeks) were subjected to ROS accumulation examination by DAB staining. Scale bar, 1 cm. Data information: The experiments were performed three times as biological replicates, with similar results. The exact number (n) and p values are shown in the source data.",
    "ncbi_link": "Gmlmm1: 100499640"
  },
  {
    "caption": "(A) Flg22-induced ROS burst in Gmlmm1-1, Gmlmm1-2 and Williams 82. The indicated leaves (aged 2 weeks) were subjected to flg22-induced ROS examination, and the peak relative luminescence unit (RLU) value was recorded (Mean ± SEM, n ≥ 12, n represents sample number). Data information: All the experiments were performed three times (biological replicates) with similar results. The exact n, SEM values and p values are shown in the source data.",
    "ncbi_link": "Gmlmm1: 100499640"
  },
  {
    "caption": "(B) Flg22-induced ROS burst in the CRISPR lines C9-24-13 and DN50. The indicated leaves (aged 2 weeks) were subjected to flg22-induced ROS examination, and the relative RLU value was recorded (Mean ± SEM, n ≥ 9, n represents sample number). Data information: All the experiments were performed three times (biological replicates) with similar results. The exact n, SEM values and p values are shown in the source data.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(C) Suppression of flg22-induced ROS production in Arabidopsis by GmLMM1. The GmLMM1 gene was introduced into Arabidopsis WT (Col-0) plants by Agrobacterium-mediated transformation. Two independent T2 lines were subjected to flg22-induced ROS examination (Mean ± SD, n ≥8, n represents sample number, ***, p < 0.001, Student's t-test). The protein expression is shown. Data information: All the experiments were performed three times (biological replicates) with similar results. The exact n, SEM values and p values are shown in the source data.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": "Suppression of flg22-induced (D) ROS production in N. benthamiana by GmLMM1. The indicated constructs were transiently expressed by Agrobacterium-mediated transient expression for 2 days and subjected to flg22-induced ROS examination. GmLMM1K564E contains a mutation at the predicted ATP binding site without kinase activity. GFP was used as a control (Mean ± SD, n = 6, n represents sample number, **, p < 0.01, ***, p < 0.001, Student's t-test). The protein expression is shown in the lower panel. Data information: All the experiments were performed three times (biological replicates) with similar results. The exact n, SEM values and p values are shown in the source data.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": "E) Suppression of chitin-induced (E) ROS production in N. benthamiana by GmLMM1. The indicated constructs were transiently expressed by Agrobacterium-mediated transient expression for 2 days and subjected to ROS examination. GmLMM1K564E contains a mutation at the predicted ATP binding site without kinase activity. GFP was used as a control (Mean ± SD, n = 6, n represents sample number, **, p < 0.01, ***, p < 0.001, Student's t-test). The protein expression is shown in the lower panel. Data information: All the experiments were performed three times (biological replicates) with similar results. The exact n, SEM values and p values are shown in the source data.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": "(F) Inhibition of XEG1-induced cell death in N. benthamiana by GmLMM1. The indicated constructs were transiently expressed in N. benthamiana 1 day before infiltration of Agrobacterium containing the XEG1 or GFP vector. The cell death phenotypes were visualized 5 days later. Protein expression of GmLMM1-HA and GmLMM1K564E-HA is shown in the lower panel.",
    "ncbi_link": "GmLMM1: 100499640
XEG1: 20663425"
  },
  {
    "caption": "(A) Identification of GmLMM1-interacting proteins by IP-MS analysis. GmLMM1-FLAG was transiently expressed in Arabidopsis protoplasts, purified by anti-FLAG M2 agarose, and subjected to mass spectrometry analysis. The complete list is shown in the source data.",
    "ncbi_link": "FLAG: 
GmLMM1: 100499640"
  },
  {
    "caption": "(B) Interactions of GmLMM1 with PRR receptors. The indicated constructs were transiently expressed in N. benthamiana leaves and subjected to luciferase complementation assay. GmFLS2 (Gm08G083300) is the closest homolog of FLS2 in soybean. GmILPA1 was used as a negative control. The protein interaction intensity is shown by the relative luminescence unit (RLU) (Mean±SD, n ≥ 6, n represents sample number, p<0.05, Student's t-test, different letters indicate significant difference). Immunoblots show the levels of protein expression. Data information: The experiments were performed three times as biological replicates, with similar results.",
    "ncbi_link": "FLS2: 
Gm08G083300: 
GmILPA1: 
GmFLS2: 100817960"
  },
  {
    "caption": "(C) Suppression of flg22-induced NbFLS2-NbBAK1 interaction by GmLMM1. NbFLS2 and NbBAK1 were co-expressed in N. benthamiana along with GmLMM1 or GmLMM1L407H, treated with H2O or flg22 and subjected to co-IP assays. Data information: The experiments were performed three times as biological replicates, with similar results.",
    "ncbi_link": "BAK1: 
FLS2: 
GmLMM1: 100499640"
  },
  {
    "caption": "(D Suppression effect of GmLMM1 on the flg22-induced interaction of GmFLS2 with GmBAK1a (D) Data information: The experiments were performed two times (D as biological replicates, with similar results.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": "E) Suppression effect of GmLMM1 on the flg22-induced interaction of GmFLS2 with GmBAK1b (E). Data information: The experiments were performed two times E), as biological replicates, with similar results.",
    "ncbi_link": "GmLMM1: 100499640"
  },
  {
    "caption": " In ThP1 cells co-infected with a HIV1-GFP virus and a HIV1-LUC virus, nuclear foci contain mixtures of both viruses. (D) Dual-color image shows RNA-FISH against GFP (red) and RNA-FISH against LUC (green). Arrows show foci containing both GFP vRNA and LUC vRNA. The bottom row shows the boxed region magnified, with GFP vRNA and LUC vRNA displayed separately and in combination. See Appendix Fig. S7. ",
    "ncbi_link": "GFP: 
LUC: "
  },
  {
    "caption": " (F) Scatter plot shows intensities of GFP RNA and LUC RNA in colocalizing foci with the Spearman correlation r and associated p-value. ",
    "ncbi_link": "GFP: 
LUC: "
  },
  {
    "caption": "(B) Green image shows RNA-FISH against NEAT1.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": " (D) Boxplots show Pearson correlations r between vDNA (EdU) and CPSF6, NEAT1 or SC35 in 17-19 regions of interest (ROIs). Central lines in boxes define medians, top and bottom limits define upper and lower quartiles, respectively. Whiskers show the full data range, except for outliers. Grey dots are individual data points. Significance of positive or negative correlations was assessed using the Costes method of random ROI shifts. Highly significant (p<0.01) positive correlations between vDNA and CPSF6 intensities are found in 16 out of 19 ROIs; highly significant negative correlations between vDNA and NEAT1 are found in 19/19 ROIs, and highly significant positive correlations between vDNA and SC35 are found for 16/17 ROIs. Data are from one experiment. For CPSF6, the experiment was repeated with similar results. ",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": " The left panel shows the timeline of infection and/or drug exposure experiments. (A-D) Percentage of GFP positive cells at 3 and 7 days post-infection analyzed by FACS in absence of EdU. (A) Uninfected control cells. (B) Untreated, infected ThP1 cells fixed at 3 d (72 h) p.i. (C) Infected cells were exposed to NVP for 72 h, then NVP was washed out and cells were cultured for another 96 h and fixed at 7 d p.i. (D) Infected cells were cultured for 72 h p.i., then NVP was washed out and cells were exposed to the nuclear import inhibitor PF74 for another 96 h and fixed at 7 d p.i. (E-H) Multicolor images of ThP1 cells infected with a GFP-reporter virus. vRNA (RNA-FISH) is labeled in red, GFP in green, and nuclei (DAPI) in blue. (E) Uninfected control cells. (F) Untreated, infected ThP1 cells fixed at 3 d (72 h) p.i. (G) Infected cells were exposed to NVP for 72 h, then NVP was washed out and cells were cultured for another 96 h and fixed at 7 d p.i. (H) Infected cells were cultured for 72 h p.i., then NVP was washed out and cells were exposed to the nuclear import inhibitor PF74 for another 96 h and fixed at 7 d p.i. The experiment was repeated three times. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " The left panel shows the timeline of infection and/or drug exposure experiments. (A-D) Multicolor images of vDNA, vRNA, DAPI and/or GFP in monocyte derived macrophages (MDMs) from two different donors, infected with HIV1. Cells from donor 1 were infected with VSV-G-pseudotyped HIV-1ΔEnv Vpx carrying a GFP reporter (A) and cells from donor 2 were infected with a VSV-G-pseudotyped HIV-1ΔEnv without Vpx (B-D). (A,B) Infected cells were left untreated and fixed at 6 d p.i. (C) Infected cells were treated with 10 µM Nevirapine (NVP) throughout the experiment and fixed at 6 d p.i. (D) Infected cells were exposed to NVP for 3 d p.i., then NVP was washed out and cells were cultured for another 4 d and fixed at 7 d p.i. Arrows in (A-D) show the position of selected vRNA foci. (E) Boxplot shows the size of DNA foci in untreated infected cells from donor 2 imaged at 7 d p.i. (B), measured by the FWHM of n=24 foci. The red line defines the median, top and bottom limits define upper and lower quartiles, respectively. Whiskers show the full data range, except for outliers. Grey dots are individual data points. (F) Boxplot shows Pearson's r, measuring colocalization of DNA with RNA foci in the same cells (n=20). Center line defines the median, top and bottom limits define upper and lower quartiles, respectively. Whiskers show the full data range, except for outliers. Grey dots are individual data points. ",
    "ncbi_link": "GFP: 
Env: 155971
Vpx: 1490006"
  },
  {
    "caption": "Boxplots (central band = median, boxes = Quartiles, whiskers = 1.5 * interquartile range), illustrating the differences in GE180 PET (A) compared between wild type C57BL/6 mice (n=43) and APPNL-G-G (n=15).",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "B Boxplots (central band = median, boxes = Quartiles, whiskers = 1.5 * interquartile range), illustrating the differences in the rate of change in Florbetaben PET (B) compared between wild type C57BL/6 mice (n=43) and APPNL-G-G (n=15).",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "A-C Coronal (top row) and axial (bottom row) slices of average 18-F GE-180 TSPO (microglia) tracer and 18F-florbetaben amyloid-PET split up by group (A - C): C57BL/6 (A), APPNL-G-F mice subgroup with a low (< median) GE-180 PET (B), and the APPNL-G-F mice subgroup with a high (> median) GE-180 PET (C). APPNL-G-F mice with low baseline GE180 PET levels showed faster increase in Florbetaben PET between 5 and 10 months (B) compared to those at high baseline level of GE-180 PET (C).",
    "ncbi_link": "APP: 11820"
  },
  {
    "caption": "(B-D) Kaplan-Meier survival  plots comparing the survival  probability of all melanoma patients  (B), BRAF-mutated patients  (C) and BRAF  wild-type (WT) patients  (D) with high- (magenta) and low (black) MCUA mRNA expression.",
    "ncbi_link": "BRAF: 673
MCU: 90550"
  },
  {
    "caption": "(E-G) Kaplan-Meier survival  plots comparing the survival  probability of patients  of indicated cancer types that are divided into either high- (magenta) or low (black) MCUA mRNA expression. P-values were calculated by using a log-rank test. Abbreviations: KICH  = kidney chromophobe; KIRC  =  kidney renal clear cell carcinoma; KIRP  = kidney renal papillary cell carcinoma; LUAD  = lung adenocarcinoma; LUSC  =  lung squamous cell carcinoma; PAAD  = pancreatic adenocarcinoma.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(C) Representative images of the migrated stained 1205Lu  shCTRL (black frame), shMCU_1 (darker blue frame) and shMCU_2 (lighter blue frame) cells on the lower side of the insert. (D) Quantification of the transwell migration in 1205Lu  stable MCUA_KD lines, based on the number of stained  cells (n=4 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(E) Representative images of 1205Lu  shCTRL (black frame), shMCU_1 (darker blue frame) and shMCU_2 (lighter blue frame) melanoma spheroids  after 72 h invasion  in collagen. Live cells   are shown in green. Scale bar: 100 µm. (F) Quantification of 1205Lu  stable  MCUA_KD spheroid core size (n=6 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU  cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(G) Representative images of WM3734  shCTRL (black frame), shMCU_1 (darker orange frame) and shMCU_2 (lighter orange frame) melanoma spheroids. Live cells are shown in green. Scale bar: 100 µm. (H) Quantification of WM3734  stable MCUA_KD spheroid core size  (n=5 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(L) Representative images of 451Lu  wild-type (grey frame), 451Lu-BR3 (lighter green frame), WM983B  wild-type (grey frame) and WM983B-BR (darker green frame) melanoma spheroids   after 72 h invasion  in collagen. Live cells  are shown in green. Scale bar: 100 µm. (M-N) Quantification of 451Lu  versus 451Lu-BR3 (M) and WM983B  versus  WM983B-BR (N)  spheroid core size   (n≥9 biological replicates/condition, shown also by individual data points). Data information: Data are presented as mean ± SEM. Statistical significance was determined using unpaired, two‐tailed Student's t‐test (shMCU  cells were compared to their respective control, shCTRL), (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(A-C) Mitochondrial hydrogen peroxide  (H2O2) measurement in 1205Lu  and WM3734  with and without stable  MCUA_KD using mito-HyPer. Exemplary ratiometric images (F505 nm/F420 nm) are shown for all conditions (A). Scale bar: 10 µm. Quantification of mito-HyPer  ratio in 1205Lu  (B) and WM3734  (C) under resting state (1205Lu  ─ shCTRL: n=217 cells from 6 biological replicates; shMCU_1: n=197 cells from 7 biological replicates; shMCU_2: n=212 cells from 7 biological replicates; WM3734  ─ shCTRL: n=104 cells from 6 biological replicates; shMCU_1: n=107 cells from 7 biological replicates; shMCU_2: n=114 cells from 7 biological replicates). Data information: All data are presented as mean ± SEM. and were measured in Ringer's buffer containing 0.5 mM Ca2+  statistical significance was determined using unpaired, two‐tailed Student's t‐test, (*) p < 0.05; (**) p < 0.01; (***) p < 0.005. In all statistical analyses, KD cells were compared to their respective control.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(D-F) Cytosolic hydrogen peroxide (H2O2) measurement in 1205Lu  and WM3734  with and without stable MCUA_KD using HyPer. Exemplary ratiometric images (F505 nm/F420 nm) are shown for all conditions (D). Scale bar: 10 µm. Quantification of HyPer  ratio in 1205Lu  (E) and WM3734  (F) under resting state (1205Lu  ─ shCTRL: n=232 cells from 6 biological replicates; shMCU_1: n=290 cells from 6 biological replicates; shMCU_2: n=290 cells from 6 biological replicates; WM3734 ─ shCTRL: n=443 cells from 9 biological replicates; shMCU_1: n=297 cells from 9 biological replicates; shMCU_2: n=233 cells from 9 biological replicates). Data information: All data are presented as mean ± SEM. and were measured in Ringer's buffer containing 0.5 mM  Ca2+ statistical significance was determined using unpaired, two‐tailed Student's t‐test, (*) p < 0.05; (**) p < 0.01; (***) p < 0.005. In all statistical analyses, KD cells were compared to their respective control.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(I-K) Mitochondrial glutathione redox potential, measured with mito-Grx1-roGFP2 in 1205Lu  and WM3734  with and without stable MCUA_KD. Representative ratiometric images (F385 nm/F475 nm) are shown for all conditions (I). Scale bar: 10 µm. Quantification in 1205Lu  (J) and WM3734  (K) under resting state (1205Lu ─ shCTRL: n=231 cells from 10 biological replicates; shMCU_1: n=176 cells from 7 biological replicates; shMCU_2: n=164 cells from 7 biological replicates; WM3734  ─ shCTRL: n=127 cells from 7 biological replicates; shMCU_1: n=142 cells from 7 biological replicates; shMCU_2: n=116 cells from 7 biological replicates). Data information: All data are presented as mean ± SEM. and were measured in Ringer's buffer containing 0.5 mM Ca2+ statistical significance was determined using unpaired, two‐tailed Student's t‐test, (*) p < 0.05; (**) p < 0.01; (***) p < 0.005. In all statistical analyses, KD cells were compared to their respective control.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(G-I) Mitochondrial ATP, measured using mito-ATEAM  in 1205Lu  and WM3734  with and without stable MCUA_KD. Exemplary ratiometric images (FRET/CFP) are shown for all conditions (G). Scale bar: 10 µm. Quantification of basal levels in 1205Lu  (H) and WM3734  (I) (1205Lu  ─ shCTRL: n=141 cells from 14 biological replicates; shMCU_1: n=143 cells from 12 biological replicates; shMCU_2: n=143 cells from 13 biological replicates; WM3734  ─ shCTRL: n=122 cells from 12 biological replicates; shMCU_1: n=103 cells from 12 biological replicates; shMCU_2: n=99 cells from 13 biological replicates). Data information: Statistical significance was determined using unpaired, two‐tailed Student's t‐test, (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "(J) Exemplary confocal microscope  images of the   mitochondrial network  (blue: DAPI staining  of the nucleus; green: TOMM20 staining  of mitochondria); scale bar: 50 µm. (K-O)  Electron microscopy of mitochondria  of stable  MCUA_KD cell lines. (K) Exemplary images of stable  MCUA_KD cells' mitochondria. Scale bar: 500 nm. (L-O) Quantification of mitochondrial  diameter (L and N) and intercristae  distance (M and O) of 1205Lu  (L and M) and WM3734  (N and O) cells with and without stable MCUA_KD, presented as boxplot. The box presents the 25 %- quartile, median and 75 %-quartile, the X represents the mean and the whiskers the minimum and maximum, outliers are represented as dots (mitochondrial  diameter: 1205Lu  ─ shCTRL: n=47 technical replicates; shMCU_1: n=44 technical replicates; shMCU_2: n=40 technical replicates; WM3734  ─ shCTRL: n=35 technical replicates; shMCU_1: n=52 technical replicates; shMCU_2: n=38 technical replicates; intercristace  distance: 1205Lu  ─ shCTRL: n=330 technical replicates; shMCU_1: n=285 technical replicates; shMCU_2: n=255 technical replicates; WM3734  ─ shCTRL: n=352 technical replicates; shMCU_1: n=433 technical replicates; shMCU_2: n=357 technical replicates). Data information: Statistical significance was determined using unpaired, two‐tailed Student's t‐test, (*) p < 0.05; (**) p < 0.01; (***) p < 0.005; no asterisk means no statistical significance (p > 0.05).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "B, qRT-PCR of piwi-1 relative to GAPDH in RNAi animals as indicated, 2dpi. Circles represent individual biological replicates averaged from 3 technical replicates.",
    "ncbi_link": "GAPDH: 
piwi-1: "
  },
  {
    "caption": "D, Percentage of X1 cells from control and atm(RNAi) animals, 1dpi or unirradiated.",
    "ncbi_link": "atm: "
  },
  {
    "caption": "E, qRT-PCR of piwi-1 relative to GAPDH in RNAi animals as indicated, 2dpi. Data are averages ± SD; circles represent biological replicates; statistics represent ordinary one-way ANOVA compared to controls, ****P<0.0001, ns=not significant.",
    "ncbi_link": "piwi-1: 
GAPDH: "
  },
  {
    "caption": "F, piwi-1 fluorescent in situ hybridization (FISH) of RNAi animals as indicated, 2 dpi.",
    "ncbi_link": "piwi-1: "
  },
  {
    "caption": "A, Top: Strategy for EdU pulse and animal fixation. Bottom: Confocal images of EdU-stained atm and control RNAi animals. B, Quantification by area of EdU+ cells from A. Circles represent individual animals. Inset, expanded scale showing compressed data below. Data includes two independent experiments.",
    "ncbi_link": "atm: "
  },
  {
    "caption": "D, Confocal images of phosphohistone H3 (pH3)-stained RNAi animals after radiation exposure. Blue, DAPI. E and F, Quantification by area of pH3 cells in radiated (E) or unirradiated (F) animals after atm (solid line) and control (dashed line) RNAi.",
    "ncbi_link": "atm: "
  },
  {
    "caption": "A, Confocal images of piwi-1 FISH in RNAi animals after radiation exposure. Scale bars=250µm. B and C, Percentage of animal area occupied by piwi-1 FISH divided by total animal area, in radiated (B) or unirradiated (C) RNAi animals. D, Total number of piwi-1+ cells in RNAi animals, 7 dpi. Experiments in (A) - (D) were repeated twice.",
    "ncbi_link": "piwi-1: "
  },
  {
    "caption": "A - C, Kaplan-Meier survival curves of intact RNAi animals after radiation, n = 50 animals, repeated twice. Experiments in A and B were performed simultaneously but split into two graphs for clarity; control and atm(RNAi) values are replicated in both panels.",
    "ncbi_link": "atm: "
  },
  {
    "caption": "D, Confocal images of piwi-1 FISH in RNAi animals after exposure to 20Gy, 2dpi. Scale bars=250µm. E, Quantification by area of piwi-1+ cells in RNAi animals after 20Gy exposure, 7dpi.",
    "ncbi_link": "piwi-1: "
  },
  {
    "caption": "Western blotting for  mTORC1 and mTORC2 activity in  mESCs transduced with Rptor  and Rictor  shRNAs.",
    "ncbi_link": "Rictor: 78757
Rptor: 74370"
  },
  {
    "caption": "Images of  mESCs  transduced with Rptor and Rictor  shRNAs in 2iL. Scale bar, 400 µm.   Relative  proliferation of mESCs as in (E) (mean values ± SD, P value was calculated using two-tailed unpaired Student's t test, *P < 0.05, also hereafter in similar experiments). n = 3 biological replicates.  ",
    "ncbi_link": "Rictor: 78757
Rptor: 74370"
  },
  {
    "caption": "Images of mESCs transduced with Rptor  siRNA on different days in 2iL. siNC, transduced with a negative control; day 0 was the day of siRNA transfection, also hereafter in similar experiments. Scale bar, 400 µm.",
    "ncbi_link": "Rptor: 74370"
  },
  {
    "caption": "RNA-seq  heatmaps of the indicated pluripotency gene sets in control and INK128 (200 nM) treated mESCs in  2iL.   RNA-seq heatmaps of indicated pluripotency gene sets in Rptor WT and KO mESCs  in 2iL.  ",
    "ncbi_link": "Rptor: 74370"
  },
  {
    "caption": "Images of mESCs  transduced with  Eif4a1, Eif4e  and Eif4g1 shRNAs in  2iL. Scale bar, 400 µm.   Relative  proliferation of mESCs  as in (B) (mean values ± SD). n = 3 biological replicates.  ",
    "ncbi_link": "Eif4a1: 13681
Eif4e: 13684
Eif4g1: 208643"
  },
  {
    "caption": "Images of mESCs transduced with Larp1  shRNAs in 2iL, in control or INK128 (200 nM) treated for three days. Scale bar, 400 µm.   Relative  proliferation of mESCs as in (E) (mean values ± SD). n = 3 biological replicates.  ",
    "ncbi_link": "Larp1: 73158"
  },
  {
    "caption": "qPCR for mtDNA copy number in mESCs treated with INK128  or transduced with Rptor shRNAs in 2iL (mean values ± SD). n = 3 biological replicates.",
    "ncbi_link": "Rptor: 74370"
  },
  {
    "caption": "Images of mESCs transduced with Rptor  or Rictor shRNAs in SL. Scale bar, 400 µm.   Relative proliferation  of mESCs as in (A) (mean values ± SD). n = 3 biological replicates.  ",
    "ncbi_link": "Rictor: 78757
Rptor: 74370"
  },
  {
    "caption": "Images of mESCs transduced with  Eif4a1, Eif4e  and Eif4g1  shRNAs in SL. Scale bar, 400 µm.",
    "ncbi_link": "Eif4a1: 13681
Eif4e: 13684
Eif4g1: 208643"
  },
  {
    "caption": "The profile of EphA2 expression in different cells is indicated. (B) Murine B cells and T cells were purified from spleens using a cell sorter, total RNA was isolated from murine B cells, T cells, BMDCs, BMDMs, AMs and AECs. Shown is mean ± SD. Data represent three independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(A-B) ELISA of IL-1β and IL-18 in BALF samples were from wild-type (WT) and EphA2-kockout (KO) mice (n=3 per strain) on day 1 and day 3 after intranasal infection with reovirus (4×104 PFU per mouse). Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "Cell number of BALF samples were from wild-type (WT) and EphA2-kockout (KO) mice (n=3 per strain) on day 1 and day 3 after intranasal infection with reovirus (4×104 PFU per mouse). Shown is mean ± SD. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "Cell number and category of BALF samples were from wild-type (WT) and EphA2-kockout (KO) mice (n=3 per strain) on day 1 and day 3 after intranasal infection with reovirus (4×104 PFU per mouse). Shown is mean ± SD. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(F) Hematoxylin and eosin (H&E)-staining of lung sections were from EphA2+/+ and EphA2−/− mice intranasally infected with reovirus (4×104 PFU per mouse) on day 0, day 1 and day 3. Scale bars represent 200μm.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(G) Immunoblot analysis of EphA2 and IL-1β in lung homogenates were from wild-type (WT) and EphA2-kockout (KO) mice on day 1 and day 3 of intranasal infection with reovirus (4×104 PFU per mouse), β-actin served as a loading control throughout.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "Quantitative RT-PCR analysis of mRNA encoding various cytokines (IL-4, IL-5, IL-13 in lung samples from wild-type (WT) and EphA2-knockout (KO) mice (n=4 per strain) sensitized with ova; results presented relative to β-actin. Shown is mean ± SD. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three or four independent biological replicates.",
    "ncbi_link": "β-actin: 11461
EphA2: 13836
IL-13: 16163
IL-4: 16189
IL-5: 16191"
  },
  {
    "caption": "Quantitative RT-PCR analysis of mRNA encoding various cytokines IL-33) in lung samples from wild-type (WT) and EphA2-knockout (KO) mice (n=4 per strain) sensitized with ova; results presented relative to β-actin. Shown is mean ± SD. (C) ELISA analysis of IL-33 in lung tissue homogenate samples from wild-type (WT) and EphA2-knockout (KO) mice (n=3 per strain) sensitized with ova. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three or four independent biological replicates.",
    "ncbi_link": "β-actin: 11461
EphA2: 13836
IL-33: 77125"
  },
  {
    "caption": "(D-G) ELISA analysis of IL-4, IL-13, IL-1β and IL-18 in lung tissue homogenate samples from wild-type (WT) and EphA2-knockout (KO) mice (n=3 per strain) sensitized with ova. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three or four independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(H) Cell number and category of BALF samples from wild-type (WT) and EphA2-knockout (KO) mice (n=3 per strain) sensitized with ova. Shown is mean ± SD. Data information: Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. *P<0.05, **P <0.01 and ***P<0.001 (unpaired t test). Data represent three or four independent biological replicates.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(I) H&E staining and PAS staining of lung sections from wild-type (WT) and EphA2-knockout (KO) mice sensitized with ova. Scale bars represent 200μm.",
    "ncbi_link": "EphA2: 13836"
  },
  {
    "caption": "(C) The indicated plasmids of HA-tagged full-length EphA2 and EphA2 truncation mutants were respectively transfected into HEK293T cells along with Myc-tagged NLRP3, and then cell lysates were immunoprecipitated with anti-Myc antibody, followed by western blot analysis with anti-HA antibody and anti-Myc Antibody. Data information: The position of protein markers (shown in kDa) is indicated on the right-hand side. Data are representative of three independent biological replicates.",
    "ncbi_link": "HA: 
Myc: 
EphA2: 13836
NLRP3: 216799"
  },
  {
    "caption": "(D) The indicated plasmids of HA-tagged full-length NLRP3 and NLRP3 truncation mutants were respectively transfected into HEK293T cells along with Myc-tagged EphA2, and then cell lysates were immunoprecipitated with anti-Myc antibody, followed by western blot analysis with anti-HA antibody and anti-Myc antibody. Data information: The position of protein markers (shown in kDa) is indicated on the right-hand side. Data are representative of three independent biological replicates.",
    "ncbi_link": "HA: 
Myc: 
EphA2: 13836
NLRP3: 216799"
  },
  {
    "caption": "(A) The indicated plasmids of Myc-tagged NLRP3 and GFP-tagged EphA2 were transfected into HEK293T cells and then cell lysates were immunoprecipitated with the anti-Myc antibody, followed by western blot analysis with the anti-p-Tyr antibody, anti-GFP and anti-Myc.",
    "ncbi_link": "GFP: 
Myc: 
EphA2: 13836
NLRP3: 216799"
  },
  {
    "caption": "(C) The indicated plasmids of Myc-tagged wild-type NLRP3 or its mutants Y132F, Y164F, Y251F, Y570F and Y589F were respectively transfected into HEK293T cells along with GFP-tagged EphA2, and then cell lysates were immunoprecipitated with the anti-Myc antibody, followed by western blot analysis with the anti-p-Tyr antibody, anti-HA antibody and anti-Myc antibody.",
    "ncbi_link": "GFP: 
Myc: 
EphA2: 13836
NLRP3: 216799"
  },
  {
    "caption": "(D) Immunoblot analysis of EphA2, ASC, NLRP3, caspase-1 and IL-1β in HEK293T cells were co-transfected with 200ng EphA2, 40ng ASC, 40ng caspase-1 and 200ng IL-1β, vector or wild NLPR3 or Y132F as indicated. The position of protein markers (shown in kDa) is indicated on the right-hand side.",
    "ncbi_link": "ASC: 
caspase-1: 
IL-1β: 
EphA2: 13836
NLPR3: 216799"
  },
  {
    "caption": "(C-D) Confocal microscopy analysis of HEK293T cells transfected with flag-ASC and Myc-tagged vector or Myc-tagged NLRP3 or Myc-tagged NLRP3 Y132F. Cells were stained with anti-flag (1:200), anti-Myc (1:200), followed by Alexa Fluor 488 goat anti-rabbit secondary antibody (green) or Alexa Fluor 594 goat anti-mouse secondary antibody (red). DAPI served as the nuclei marker (blue). Data information: Scale bars represent 50μm. Each symbol represents an independent experiment; small horizontal lines indicate the average of triplicates. **P <0.01 and ***P<0.001 (unpaired t test). Data represent three independent biological replicates.",
    "ncbi_link": "ASC: 
flag: 
Myc: 
NLRP3: 216799"
  },
  {
    "caption": " d Reverse transcription PCR (RT-PCR)-sequence analyses of total brain mRNA show the A-to-G mutation in pos. 0 and two diagnostic silent mutations at pos. -11 and -14 in the pore loop encoding gene segment in Grin2a+/+, Grin2aS/S, Grin2a+/S mice. In Grin2a+/S mice, the overlay of two different colored "nucleotide" peaks, at position 0, -11, and -14 indicate equimolar amounts of mRNA from the Grin2a+ and the targeted Grin2aS alleles. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " e Immunoblots of forebrain protein lysates of 4-week-old mice (Supplementary Fig. 2) indicate no genotype-specific differences of GluN1, GluN2A, and the AMPAR subunit GluA1 expression relative to the β-actin levels (p > 0.05). The levels of PSD95 and αCaMKII (in its phosphorylated state, pCaMKII) are also comparable between genotypes relative to the GAPDH expression. The GluN2B expression level in the membrane fraction was significantly increased in Grin2aS/S mice when compared to Grin2a+/+ and Grin2a+/S mice but not in the levels of total protein lysates (for statistics: Supplementary Statistics to Fig. 1). The number of mice is given in brackets. Error bars represent mean ± SEM. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " a (left) In the absence of extracellular Mg2+ the synaptic AMPA/NMDA ratio of CA1 pyramidal cells in acute hippocampal slices is not altered in Grin2a+/S and Grin2aS/S mice compared to control littermates. (right) In the presence of extracellular Mg2+ the strong reduction of the AMPA/NMDA ratio in Grin2aS/S mice relates to the increased NMDA currents at CA1 synapses (Tukey's test). Example traces are depicted to the right of each bar graph. Data from the same experimental group were pooled across animals and are presented as mean ± SEM (see also ref. 35) with p < 0.05 being designated as statistically significant. Numbers in bar graphs indicate the number of slices. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " b Paired-pulse facilitation at CA3-to-CA1 synapses excluded strong alterations of presynaptic function in mutant mice. The stimulation strengths (in nC) necessary to elicit a pre-volley of 1.0 and 1.5 mV and the resulting fEPSP amplitudes were comparable in all genotypes but showed only a trend towards lower fEPSP amplitudes recorded at 1.5 mV pre-volley amplitudes in Grin2aS/S mice. The fEPSP amplitudes necessary to elicit a just detectable population spike (1) and a population spike of 2 mV amplitude (2) and the paired-pulse facilitation ratio (PPF) at an interstimulus interval of 50 ms did not indicate any synaptic impairments in Grin2aS/S and Grin2a+/S mice compared to WT littermates. The number of slices is indicated in the bar graphs or in brackets. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " c Field LTP (fLTP) at CA3-to-CA1 synapses, induced by tetanic stimulation in slices (1 s; 100 Hz; arrow), was comparable in all three genotypes. The inset in c gives a schematic view of the stimulating (white arrow) and the recording (green arrow) electrode positions in str. radiatum (r) and str. oriens (o). d Similarly, CA1-to-CA3 fLTP (induction: 2 × 1 s; 100 Hz; arrow) in freely moving mice was comparable between Grin2aS/S and Grin2a+/+ mice. The inset shows a Nissl-stained slice of one recorded mouse post mortem. e In mutant mice, but not in control littermates, the GluN2B-containing NMDAR contributes significantly to the magnitude of LTP, since LTP was significantly reduced by the GluN2B-specific antagonist CP101,106 (CP). Recordings of the non-tetanized control pathway in c and e are given as dashed lines. Error bars represent mean ± SEM (for statistics: Supplementary Statistics to Fig. 2). ",
    "ncbi_link": "GluN2B: 
Grin2a: 14811"
  },
  {
    "caption": " aGrin2aS/S mice had a reduced body weight (by 18% in adults), significantly lower score in nesting and in overnight burrowing activity (filled circles: 30-week-old mice, white dots: 18-week-old mice). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " b Grin2aS/S mice showed the clasping reflex. c During the 12 h dark phase on the Lafayette running wheel the running distance is reduced in Grin2aS/S mice. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " d Nissl staining revealed unaltered cell density throughout the brain (top) and layering of hippocampal subfields, including CA1 (bottom), in Grin2aS/S mice compared to Grin2a+/+. Error bars represent mean ± SEM. e In the TUNEL assay no apoptotic cells could be detected in the hippocampus of Grin2aS/S mice, compared to the staining of the nuclease-treated positive control slice. f No aberrant mossy fiber sprouting in either genotype in the dentate gyrus inner (IML) and outer molecular layer (OML) can be found by Timm staining of coronal sections. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " g The distribution of NeuN-positive neurons and of GFAP-positive glial cells are indistinguishable between Grin2aS/S and Grin2a+/+ mice. Mossy fiber projections visualized by anti-calbindin (CB) staining, as well as numbers of parvalbumin (PV)-positive interneurons are similar between both genotypes. Anti-GluA1 immunosignal in all hippocampal layers is comparable between brain sections of Grin2aS/S mice and control littermates. CA1 cornu ammonis region 1, CA3 cornu ammonis region 3, DG dentate gyrus, mol stratum moleculare, ori stratum oriens, rad, stratum radiatum. Scale bars in d-g are in mm. The number of animals is given below the bars. For the Nissl stain, Tunnel test and Timm stain 3 mice were used per genotype. For the immunohistological analysis of glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), Calbindin (CB), and Parvalbumin (PV) five mice and for the GluA1 immunofluorescence stain, three mice were used (for statistics: Supplementary Statistics to Fig. 3). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " a Mortality curve showing that none of the Grin2a+/+ controls were affected, while audiogenic seizures (AGSs) followed by respiratory arrest (RA) were induced in all Grin2aS/S mice and in a subset of heterozygous Grin2a+/S mutants during the 11 kHz tone exposure [4 repetitions × 20 s tone, 2 s brake; pink squares; p < 0.0001 by Log-rank (Mantel-Cox) test]. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": "b The c-Fos immunoreactivity was specifically increased in the hypothalamus (VMH), the inferior colliculus (IC), and periaqueductal gray (PAG) but not in the hippocampus (HPC) of a resuscitated Grin2aS/S mouse 90 min after AGS when compared to tone-exposed Grin2a+/+ littermates.",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " c Memantine i.p. injection in Grin2aS/S mice, 3 h before tone exposure, rescued AGS susceptibility in Grin2aS/S mice. The rescue effect could still be observed in four out of eight, and in two out of eight, mice 27 and 51 h after memantine treatment, respectively. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " d Increased c-Fos immunofluorescence (in grayscale) in the medial amygdala (MeA) and the VMH of a Grin2aS/S animal with AGS (saline injection) compared to a memantine rescued Grin2aS/S littermate. In the paraventricular nucleus of the thalamus (PVT), the hippocampus (HPC) and cortex (Cx) there was no difference in c-Fos expression between memantine-injected and saline-injected animals (for fluorescence images, see Supplementary Fig. 5). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " f Decreased c-Fos DAB immunosignal in an MK-801 AGS-rescued Grin2aS/S animal (bottom) in the medial amygdala (MeA), the VMH and the PVT when compared to saline-injected Grin2aS/S littermate (top). Scale bars are in mm (for statistics: Supplementary Statistics to Fig. 4). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " a (left) Peak frequencies during exploration and rapid eye movement (REM) sleep for theta (0-15 Hz, left diagrams) and gamma oscillations (15-200 Hz, right diagrams) in all genotypes. During exploration, the average theta range peak frequencies were at 8.61 ± 0.07 and 8.75 ± 0.28 Hz for Grin2a+/+ mice and Grin2a+/S mice, respectively. In Grin2aS/S mice the theta range peak frequency was significantly slower, measuring 7.43 ± 0.24 Hz (Kruskal Wallis test, p = 0.0159). During REM sleep the average frequency ranges of Grin2a+/+ and Grin2a+/S mice were around 7.00 ± 0.20 Hz whereas Grin2aS/S mice had a lower but not significantly different range 6.71 ± 0.22 Hz. a (right) No significant differences on the low and high gamma frequency bands-ranges between 20-100 Hz and 100-200 Hz, respectively111-could be detected between genotypes, neither during exploration nor in REM sleep. The number of mice used in this experiment are given with the name of the genotypes. ",
    "ncbi_link": "REM sleep: 
Grin2a: 14811"
  },
  {
    "caption": " b (left) Grin2aS/S and Grin2a+/S mice show reduced theta-gamma phase-amplitude coupling as determined by the modulation index (MI) in the low gamma component in CA1 (white arrowheads) during awake and REM sleep states. b (right) For Grin2aS/S the MI value dropped significantly during exploration and REM sleep although the MI reduction reached significance only during exploration (one-way ANOVA, Kruskal-Wallis test). Numbers below bars of bar graphs indicate the number of animals. Error bars represent mean ± SEM. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " b Similarly, the exploratory behavior of Grin2aS/S mice remained high in all three successive 6 min exposure sessions to five novel objects (ITI = 4 min), as exemplified by traces of the animal's movement on the right. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " c (left) The time of first fall (Cliff Avoidance Reflex, CAR) was significantly reduced for Grin2aS/S and Grin2a+/S mice. c (right) In a 60-min session Grin2aS/S mice showed a significantly increased number of falls compared to wild-type mice. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": "d (left) In the three-chamber sociability test Grin2aS/S mutants had a significantly reduced preference to explore the stimulus mouse over the object compared to Grin2a+/S and Grin2a+/+ littermates. d (right) Occupancy heat maps in the three-chamber sociability test show a representative example of a Grin2aS/S mouse with a reduced preference for another mouse versus an inanimate object. The social preference is visible for Grin2a+/+ and Grin2a+/S mice. The occupancy is color-coded separately for each group and translates to a % given in white numbers on the key for each genotype.",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " e During the novel object recognition test, Grin2aS/S mice displayed significantly more interactions with the two objects in both the sample and test runs compared to their Grin2a+/S and Grin2a+/+ littermates. During the test run, only the Grin2a+/S and Grin2a+/+ showed a significant preference for the novel object over the familiar object. There was no significant novelty preference in the Grin2aS/S mice.",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " f During the sample run in the Y-maze Grin2aS/S mice made significantly more total arm entries. In the test run, Grin2a+/+ and Grins2a+/S showed a preference for the unexplored novel Y-maze arm, whereas Grin2aS/S mice showed a lack of novelty preference. The numbers of mice are shown in brackets or below the bars of bar graphs. Chance levels (Ch.) are indicated by dashed lines. Error bars represent mean ± SEM (for statistics: Supplementary Statistics to Fig. 7). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " c Morris watermaze. In the standard Morris watermaze task (left graph) the path length to reach the hidden platform decreased across training blocks for Grin2a+/+ and Grin2a+/S mice but not for Grin2aS/S mice. Two probe trials were conducted after 12 and 24 training trials (P1 and P2, respectively) during which the platform was removed from the pool. At both P1 and P2 (right bar graphs) the Grin2aS/S mice failed to search for the platform in the target quadrant. AdjL adjacent left, Target fixed location of the hidden escape platform during acquisition, AdjR adjacent right, Opp opposite of target quadrant. Dashed lines indicate chance levels. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " d Rewarded alternation. (left) In the T-maze rewarded alternation task (right) spatial working memory performance was substantially impaired in Grin2aS/S mice. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " e Contiguous task. In the contiguous version of the conditional T-maze task (with floor inserts covering the entire T-maze; white Perspex versus gray wire mesh), Grin2a+/+ and Grin2aS/S mice were able to associate a particular floor insert with the location of the reward in either the left or the right goal arm. ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": " f Discontiguous task. Separate groups of mice were trained in the discontiguous version of this conditional task, in which the floor insert cues were now limited to the start arm only. Grin2a+/+ mice readily acquired the task, but Grin2aS/S mice failed to learn. The numbers of mice are shown in brackets or below the bars of bar graphs. Chance levels (Ch.) are indicated by dashed lines. Error bars represent mean ± SEM (for statistics: Supplementary Statistics to Fig. 8). ",
    "ncbi_link": "Grin2a: 14811"
  },
  {
    "caption": "Overexpression of USP36 promotes SUMOylation in cells. Whole cell lysates (WCL) from H1299 (A), U2OS and HeLa (B) cells transfected with control empty vector or Flag-USP36 were assayed by IB.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "H1299 cells transfected with WT USP36 or the indicated mutants and His-SUMO2 were subjected to Ni2+-NTA agarose beads pull down (PD) followed by IB using anti-SUMO2/3 antibody.",
    "ncbi_link": "His: 
SUMO2: 6613
USP36: 57602"
  },
  {
    "caption": "USP36 SUMOylates PARP1 in vitro. Recombinant T7-PARP1 protein (0.1 μM) was incubated with SUMO E1 (30 nM), Ubc9 (50 nM), SUMO2 (4 μM) in the presence of USP361-800 (50 nM) and/or ATP (2.5 mM) at 30ºC for 5 hours and then assayed by IB.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "USP36 SUMOylates Nhp2 and Nop58 in vitro. In vitro SUMOylation assays were performed by incubating recombinant Nhp2 (F, G) or Nop58 (H) (0.1 μM) with SUMO E1 (30 nM), Ubc9 (50 nM), SUMO2 (4 μM) in the absence or presence of USP361-800 (50 nM, 1x; 100 nM, 2x) and/or ATP (2.5 mM) at 37ºC for two hours or the indicated times. The reactions were assayed by IB using anti-Nhp2 and anti-Nop58 antibodies, respectively.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "USP36 does not change the levels of endogenous snoRNP proteins. HeLa cells infected with scrambled or the indicated USP36 shRNA lentiviruses were assayed by IB.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "USP36 promotes the binding of Nhp2 to snoRNAs. H1299 cells transfected with Flag-Nhp2 and V5-USP36 individually or together were assayed by RNA-IP with anti-Flag or control mouse IgG, followed by RT-qPCR detection of the indicated box H/ACA snoRNAs (C). Shown is one representative experiment of three independent experiments. Data were presented as mean ± SD, n=3 technical replicates. *P<0.05; **P<0.01, compared to Nhp2 alone (Student's t-test).",
    "ncbi_link": "Flag: 
V5: 
Nhp2: 55651
USP36: 57602"
  },
  {
    "caption": "(B). USP36 is required for rRNA processing. HeLa cells transfected with scr or USP36 siRNA (left panels) or infected with scr or USP36 shRNA lentiviruses (right panels) were assayed for rRNA processing by Northern blot using 5'- ETS, ITS1 and ITS2 probes as indicated.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "Knockdown of USP36 inhibits translation. HeLa cells infected with scr or USP36 shRNA lentiviruses were incubated with O-propargyl-puromycin (OPP) followed by Click-iT OPP protein synthesis assays. Representative images (C) and quantification from three independent experiments (D). Data were presented as mean ± SD, n=3 biological replicates. ***P<0.001, compared to scr control (Student's t-test). Scale bar = 50 μM.",
    "ncbi_link": "USP36: 57602"
  },
  {
    "caption": "(A) DIV 3 cortical neurons immunolabelled for PIP3. Spectrum heatmap shows fluorescence intensity. (B) DIV 8 cortical neuron transfected with GFP and immunolabelled for PIP3. Spectrum heatmap shows fluorescence intensity. (C) DIV 16 cortical neuron transfected GFP and immunolabelled for PIP3. Spectrum heatmap shows fluorescence intensity. (D) Somatic PIP3 quantification in the soma at increasing days in vitro. Data are shown as the mean +/- SEM. P values are significance measured by ANOVA with Tukey's post-hoc analysis. N=3 experiments, 60 neurons. (E) Growth cone PIP3 quantification at increasing days in vitro. Data are shown as the mean +/- SEM. P values indicate significance measured by ANOVA with Tukey's post-hoc analysis. N=3 experiments, 60 growth cones. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) PIP3 immunofluorescence in the soma of DIV 16 cortical neurons expressing p110 isoforms and GFP. Spectrum heatmap shows fluorescence intensity. (B) PIP3 immunofluorescence at the axonal growth cone of DIV 16 neurons expressing p110 isoforms and GFP. Spectrum heatmap shows fluorescence intensity. (C) Quantification of PIP3 immunofluorescence in the soma. Data are shown as the mean +/- SEM. P values indicate significance as measured by ANOVA with Tukey's post-hoc analysis. N=3 experiments, 60 neurons. (D) Graph showing PIP3 quantification of immunofluorescence at the axon growth cone. Data are shown as the mean +/- SEM. P values indicate significance measured by ANOVA with Tukey's post-hoc analysis. N=3 experiments, 60 growth cones. ",
    "ncbi_link": "GFP: 
GFP.: 
p110: 5293///5290"
  },
  {
    "caption": "(A) DIV 4 cortical neurons expressing p110 isoforms and GFP. Arrow marks the axon tip. (B) Quantification of axon length. n = 3 experiments, 45 neurons per group. (C) Quantification of dendrite length. n = 3 experiments, 45 neurons per group. (D) Quantification of the axon:dendrite length ratio. n = 3 experiments, 45 neurons per group. ",
    "ncbi_link": "GFP: 
p110: 5293///5290"
  },
  {
    "caption": "(E) DIV 14 cortical neurons expressing p110 isoforms and GFP, immunolabelled for pS6. (F) Sholl analysis of branches. n = 60 neurons per group. Data are shown as the mean +/- SEM. P values indicate significance measured by repeated measure ANOVA with Bonferonni's post-hoc test. (G) Quantification of the total neurite length. n = 3 experiments, 60 neurons per group. (H) Quantification of soma area. n = 3 experiments, 60 neurons per group. (I) Quantification of the pS6 immunofluorescence. n = 3 experiments, 60 neurons per group. ",
    "ncbi_link": "GFP: 
p110: 5293///5290"
  },
  {
    "caption": "(A) Axotomised DIV 14-16 rat cortical neurons expressing p110δ and GFP or GFP alone. Axons were cut >1000 μm from the soma imaged for 14 h. Black arrows mark the cut site, white arrows marks the axon tip. See also Movies EV7 and EV8. (B) Percentage of regenerating axons 14 h after laser axotomy. Numbers on bars are injured axons per group, from 4 experiments. (C) Quantification of axon regeneration length 14 h post-axotomy. n=9 axons for GFP, 9 for p110α, 25 for p110αH1047R and 27 for p110δ from 4 experiments. (D) Quantification of time to start of regeneration. n=9 axons for GFP, 9 for p110α, 25 for p110αH1047R and 27 for p110δ from 4 experiments. ",
    "ncbi_link": "GFP: 
p110α: 5290
p110δ: 5293"
  },
  {
    "caption": "(E) Axotomised human embryonic stem cell neurons p110δ and GFP or GFP alone. Black arrow marks the cut site, white arrows mark the axon tip. (F) Percentage of regenerating axons of human hESC neurons, Numbers on bars are injured axons per group, from 5 experiments. (G) Quantification of axon regeneration length. n=22 axons for GFP, 44 for p110δ, from 5 experiments. Data are shown as the mean +/- SEM. Data were analysed by two tailed Student's T-test. (H) Quantification of time to start of regeneration. n=22 axons for GFP, 44 for p110δ, from 5 experiments. Data are shown as the mean +/- SEM. Data were analysed by two tailed Student's T-test. ",
    "ncbi_link": "GFP: 
p110δ: 5293"
  },
  {
    "caption": "(A) Percentage of regenerating axons after laser axotomy of DIV 14-17 rat cortical neurons expressing either GFP (control) or GFP and p110δ in the presence of the indicated inhibitors, 14h after laser injury. Numbers on bars are injured axons per group.",
    "ncbi_link": "GFP: 
p110δ: 5293"
  },
  {
    "caption": "(B) Single confocal section through a DIV 16 neuron expressing p110δ and GFP (upper panels). Green colour is GFP, red is overexpressed p110δ, detected with anti-p110δ. Lower panels show p110δ and GFP in a distal axon section, and at the growth cone. Arrow indicates the axon.",
    "ncbi_link": "GFP: 
p110δ: 5293"
  },
  {
    "caption": "(C) Active ARF and total ARF6 (red) in axons of DIV 16 rat cortical neurons expressing GFP or GFP and p110δ, as indicated. Arrows indicate axons. (D) Quantification of mean axonal ARF activity and total (mean) ARF6 in DIV 16 neurons expressing GFP or GFP and p110δ n=60 axons for each condition. ",
    "ncbi_link": "GFP: 
p110δ: 5293"
  },
  {
    "caption": "(E) Kymographs showing dynamics of α9 integrin-GFP in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. (F) Quantification of α9 integrin-GFP dynamics in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. n numbers are axon sections analysed for each condition. (G) Quantification of total α9 integrin-GFP number in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. n=43 for control, 47 for co-transfected with p110δ. n numbers are axon sections analysed for each condition.",
    "ncbi_link": "GFP: 
α9 integrin: 3680
p110δ: 5293"
  },
  {
    "caption": "(H) Kymographs showing dynamics of Rab11-GFP in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. (I) Quantification of Rab11-GFP dynamics in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. n numbers are axon sections analysed for each condition. (J) Quantification of total Rab11-GFP in the distal axons of DIV 14-16 neurons, control or co-transfected with p110δ. n=43 for control, 53 for co-transfected with p110δ. n numbers are axon sections analysed for each condition. ",
    "ncbi_link": "GFP: 
p110δ: 5293
Rab11: 8766"
  },
  {
    "caption": "(D) Percentage of phospho-S6 positive cells in the RGC layer 2 weeks after delivery of AAV-Cre-GFP or AAV-GFP.",
    "ncbi_link": "GFP: 
Cre: 2777477"
  },
  {
    "caption": "G) Representative images of CTB-labelled RGC axons 4 weeks after optic nerve crush in wild type (c57bl/6), Rosa26-p110αH1047R, and Rosa26-p110δ transgenic mice injected with AAV2.Cre.GFP. Dashed line indicates crush site.",
    "ncbi_link": "GFP: 
Rosa26: 
Cre: 2777477
p110α: 5290
p110δ: 5293"
  },
  {
    "caption": "(A) Retinal sections from mice injected with AAV2 viruses as indicated, immunolabeled for phospho-S6. Blue colour is DAPI to indicate nuclei. Inset images show individual colours at the same scale as the full image. (B) Percentage of phospho S6 positive cells in the retinal ganglion layer of mice injected with AAV2.shScramble.GFP or AAV2.shPTEN.GFP. (C) Number of pS6-postive RGCs of mice injected with AAV2.GFP or AAV2.p110δ.",
    "ncbi_link": "GFP: 
p110δ: 5293
PTEN: 19211"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I) or control followed by western blot analysis (A) The basal levels of p53 normalized to GAPDH were arbitrarily set at 1.0 and the fold change is shown in (ii) (n=4).",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 or control (A-I) combined or not with a treatment with doxorubicin (Doxo) (positive control for phosphorylation of ATM and p53) (B) followed by western blot analysis.",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), ASF (C) (positive control for y-H2AX activation [29])or control (A-I) followed by western blot analysis.",
    "ncbi_link": "ASF: 6426
Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) combined or not with a treatment with wortmannin (WTN) (D) followed by western blot analysis.",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) combined or not with a treatment with NU-7441 (E,F) followed by western blot analysis.",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), XRCC4 (F) or control (A-I) combined or not with a treatment with NU-7441 (E,F), followed by western blot analysis.",
    "ncbi_link": "XRCC4: 7518
Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) followed by RT-qPCR analysis (G). In RT-qPCR analysis (G), mRNA levels were standardized against HPRT mRNA (n=3). The two panels of Fig. 1C are partion of the same gel. Statistical analysis by unpaired t-test (*P<0.05; **P<0.01). All error bars reflect SEM.",
    "ncbi_link": "HPRT: 
Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) combined or not with a treatment with MG132 (H) followed by western blot analysis (A-F, H-I).",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "Treatment of HCT116 cells with siRNA targeting Ku70 (A-I), or control (A-I) combined or not with a treatment with cycloheximide (CHX) (I) followed by western blot analysis (A-F, H-I).",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "(A) RNA affinity chromatography using the p53 5'UTR (5'p53) or a portion of the p47 5'UTR (5'p47) (depicted in (i)) and HeLa cytoplasmic extracts (CE), followed by western blot analysis (ii).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(B) IP of in cellulo RNA-protein complexes (RIP) in HCT116 cells, followed either by RT-qPCR analysis. Bar plots represent the mean and the data of two independent experiments (i) or by western blot analysis (ii). The relative p53 mRNA levels for each IP sample were normalized to the corresponding IP IgG and to the corresponding input sample and were plotted relatively to the HPRT mRNA.",
    "ncbi_link": "HPRT: 
p53: 7157"
  },
  {
    "caption": "(C) UV cross-linking of recombinant (Ku70/Ku80) with the in vitro transcribed 5'p53 with alpha 32P-GTP or alpha 32P-UTP (i). UV cross-linking of recombinant Ku70/Ku80 with the in vitro transcribed 5'p53 and the Ctrl (5'p53 antisense) with alpha 32PGTP (ii).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(A) Non polysomal (NP) and polysomal (P) fractions were extracted from HCT116 cells transfected with the siRNA Ku70 and quantitative RT-qPCR was performed using specific primers for p53 and HPRT mRNAs. The p53 mRNA levels in P and NP fractions were normalized to the input (n=3)",
    "ncbi_link": "HPRT: 3251
p53: 7157
Ku70: 2547"
  },
  {
    "caption": "(B) Western blot from H1299 (p53-null) cells treated with siRNA Ku70 or control (ii), followed by transfections of RNA constructs depicted in (i). p53 protein levels from the WT and the ΔB2 reporters depicted in (i) normalized to firefly luciferase (transfection control reporter) (iii, n=3).",
    "ncbi_link": "firefly: 
p53: 7157
Ku70: 2547"
  },
  {
    "caption": "(D) RT-qPCR analysis of Bax, TP53I3, BTG2, GADD45α and p21 after siRNA-mediated Ku or control depletion in HCT116p53+/+ or HCT116p53-/- (n=3). Relative mRNA levels were standardized against GAPDH mRNA. Statistical analysis by unpaired t-test (*P<0.05; **P<0.01; *** P<0.001 NS, non significant). All error bars reflect SEM.",
    "ncbi_link": "GAPDH: 
Bax: 581
BTG2: 7832
p21: 1026
GADD45α: 1647
p53: 7157
TP53I3: 9540
Ku: 7520///2547"
  },
  {
    "caption": "(A) Western blot analysis after treatment with Ku70 or control siRNA, followed by incubation with DMSO, etoposide (ETO) or bleomycin (BLEO) for 16 h (i). p53 levels after Ku70 depletion normalized to siRNA control for each condition (ii, n=3). All the experiments were performed with HCT116 cells. GAPDH: loading control in A, B, C. Statistical analysis by unpaired t-test (*P<0.05; **P<0.01; *** P<0.001; NS, non significant). All error bars reflect SEM.",
    "ncbi_link": "Ku70: 2547"
  },
  {
    "caption": "(B) Western blot analysis as in A, except that tricostatin A (TSA) was used after Ku/control knockdown (n=4). All the experiments were performed with HCT116 cells. GAPDH: loading control in A, B, C. Statistical analysis by unpaired t-test (*P<0.05; **P<0.01; *** P<0.001; NS, non significant). All error bars reflect SEM.",
    "ncbi_link": "Ku: 2547"
  },
  {
    "caption": "(D) RNA affinity chromatography using the 5'p53RNA and total extracts from cells treated with TSA, ETO or BLEO for 24 h, followed by western blot analysis of Ku70 quantified and normalized to the input (ii, n=3). All the experiments were performed with HCT116 cells. Statistical analysis by unpaired t-test (*P<0.05; **P<0.01; *** P<0.001; NS, non significant). All error bars reflect SEM.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(E) RNA affinity chromatography using the 5'p53RNA and total extracts from cells transfected or not with PCAF encoding plasmid for 48 h, followed by western blot analysis. All the experiments were performed with HCT116 cells.",
    "ncbi_link": "PCAF: 8850
p53: 7157"
  },
  {
    "caption": "(F) RNA affinity chromatography using the 5'p53RNA or a dsDNA and total extracts from cells transfected with HA-tagged Ku70 wild-type (WT) or mutated (Mut6E) Ku70 [25] for 48 h, followed by western blot analysis. All the experiments were performed with HCT116 cells.",
    "ncbi_link": "p53: 7157
Ku70: 2547"
  },
  {
    "caption": "(G) RNA affinity chromatography as in F, but with two additional Ku mutants (K282/338Q and K282/338R), followed by western blot of Ku70 quantified and normalized to the input and to the loading control, PTB (ii, n=3) All the experiments were performed with HCT116 cells.",
    "ncbi_link": "Ku: 2547
Ku70: 2547"
  },
  {
    "caption": "F. Segregation of c.2241C> G, p.Y747X in PPP1R13L in the studied family: The affected girl VI10, is homozygous for the causative SV p.Y747X, as are the four fetuses that were aborted. The parents are obligate carriers as shown and, of the two healthy sisters, one carries the wild allele only, and the other is heterozygous for the causative SV.",
    "ncbi_link": "PPP1R13L: 10848"
  },
  {
    "caption": "A. PPP1R13L mRNA expression level is lower in VI10 PDFs (set as 1) than in CFs.",
    "ncbi_link": "PPP1R13L: 10848"
  },
  {
    "caption": "D. WB analysis demonstrated that PPP1R13L-shRNA downregulated the putative iASPP band.",
    "ncbi_link": "PPP1R13L: 10848"
  },
  {
    "caption": "C. knockdown of PPP1R13L in CFs resulted in increased mRNA expression levels of inflammatory mediators. Differences between knockdown and control with p values (Student's t test) are indicated with asterisks in the graph.",
    "ncbi_link": "PPP1R13L: 10848"
  },
  {
    "caption": "B. ChIP assay shows that p65 is associated more strongly with inflammatory cytokine gene promoters in LPS-stimulated PDFs than in LPS-stimulated-CFs. The binding activity at the IL1B promoter was set as 1. Differences between knockdown and control with p value= 0.00436 (Student's t test) are indicated with an asterisk.",
    "ncbi_link": "IL1B: 3553"
  },
  {
    "caption": "A. WB analysis confirmed the reduced expression of iASPP in ppp1r13l knocked down cardiomyocytes.",
    "ncbi_link": "ppp1r13l: 333654"
  },
  {
    "caption": "B. qPCR showed that ppp1r13l-knocked down murine cardiomyocytes (using two alternative shRNA sequences) expressed higher level of pro-inflammatory cytokine mRNAs after 4 hrs of LPS stimulation. The expression in ppp1r13l-knocked down murine cardiomyocytes was set as 1. Genome wide expression analysis is presented in Figure 1S. Differences between knockdown and control with p values (Student's t test) are indicated with asterisks and exact values.",
    "ncbi_link": "ppp1r13l: 333654"
  },
  {
    "caption": "A wa3 hearts express higher level of Il1 than littermate WT hearts without significant changes in selected structural and regulatory genes as myosin binding protein C (Mybpc3), phospholamban (Pln), ryanodine receptor 2 (Ryr2), and sarcoglycan gamma (Sgcg). Hearts removed from perfused mice and mRNA was subjected for q PCR. Difference between knockdown and control with p values = 0.03 (Student's t test) is indicated with an asterisk.",
    "ncbi_link": "Mybpc3: 17868
Pln: 18821
Ryr2: 20191
Sgcg: 24053"
  },
  {
    "caption": "B. A scatter plot showing the deviation from normal expression by highlighting the differentially expressed genes of newborn, 7-week- and 12-week- hearts (p<0.05 threshold, calculated by Deseq algorithm \"R\"). The expression level of s100a9 was higher in wa3 mice than in WT by 2.8 times. For the full list of genes see Tables S1 and S2, and functional analyses in Figures S3-S6.",
    "ncbi_link": "s100a9: 20202"
  },
  {
    "caption": "A. LPS (5mg/Kg for 2 hrs) induced higher expression levels of cytokine genes in wa3 hearts than in littermate WT hearts. The results are presented as fold induction of untreated controls. The mRNA expression levels of Pln and Ryr2 was reduced in both wa3 and WT hearts, while of Mybpc3 and Sgcg was unchanged. For the full list see Dataset EV3 and for functional clustering in Appendix Figure S7. Differences between knockdown and control with p values =0.04998 (Student's t test) are indicated with an asterisk.",
    "ncbi_link": "Mybpc3: 17868
Pln: 18821
Ryr2: 20191
Sgcg: 24053"
  },
  {
    "caption": "E. Influence of cy3 label on the 5' and 3' end of oligo#5. Using a phosphate linker, Cy3 was added to the 5' or 3' phosphate, respectively and the oligonucleotides assayed by RT-PCR. Oligo#5 with cy3 at the 5' end showed 86% inclusion, with Cy3 at the 3' end 17% exon inclusion.F. Statistical analysis of the effect of oligonucleotide modification. The effect is significant, p=0.009, n=4.",
    "ncbi_link": "cy3: 
Cy3: "
  },
  {
    "caption": "C. Effect of oligo#5 on the truncated 5HT2C protein. Stable cell lines expressing the construct shown in panel (A) were treated with oligo#3 and oligo#5. After 48 hrs cells were separated in membrane containing fractions and soluble cytosolic supernatant. The fractions were analyzed by Western Blot using the anti-RNA1 antiserum (Figure EV1). The protein samples were on the same membrane, but the supernatant fractions were exposed about ten times longer.D. Effect of oligo#5 on the full-length 5HT2C protein. The protein was prepared as in panel (C) and analyzed using a polyclonal anti-GFP antiserum.E. Quantification of panels C and D from three independent experiments. The ratio of protein signal after oligo#3 and oligo#5 treatment is shown for RNA1 (p=0.002) and RNA2 (p=0.0003), n=3, respectively.",
    "ncbi_link": "5HT2C: 3358"
  },
  {
    "caption": "G. Effect of oligo#5 on POMC expression. The RNA from panel D was analyzed using qPCR with primers against POMC, normalized to GAPDH (3 hrs: p=0.0009; 6 hrs: p=0.02; 9 hrs: p=0.1; 12 hrs: p=0.3, n=3).",
    "ncbi_link": "GAPDH: 
POMC: 18976"
  },
  {
    "caption": "H. Effect of oligo#5 on food uptake in wild-type mice. C57BL/6 wild-type mice received a guide canulae and did not have access to food for 16 hours. After injection of 2 µg oligonucleotides, they could freely access food. The food consumption was measured by weighing the food used. A total of 52 animals were used, p=0.001 for the difference between oligo#5 and control oligonucleotides. Each of the six individual experiments showed statistically significant differences between oligo#5 and control (p<0.01 - 0.001). Control oligo: an oligonucleotide against human SMN2.",
    "ncbi_link": "SMN2: 6607"
  },
  {
    "caption": "I. Effect of oligo#5 on food uptake in ob/ob mice. Ob/obmice received oligo#5 through ICV injection, similar to panel F. However, the mice could freely access food at all times (p=0.04, n=3).",
    "ncbi_link": "ob: 16846"
  },
  {
    "caption": "(A) Western blot analysis of the immunoproteasome subunits LMP2, LMP7 and β-actin (loading control) in three PolgA+/+ and three PolgAmut/mut cell lines.",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(B) RT-qPCR analysis of immunoproteasome subunits Psmb8, Psmb9, Psmb10 in three different PolgA+/+ and three PolgAmut/mut cell lines.",
    "ncbi_link": "PolgA: 18975
Psmb10: 19171
Psmb8: 16913
Psmb9: 16912"
  },
  {
    "caption": "(C) Activity assay for the catalytic subunits of the proteasome using the pan activity-based probe (ABP) MV151, the β1/LMP2 specific LW124, and the β5/LMP7 specific MVB127 ABPs in three PolgA+/+ and three PolgAmut/mut cell lines. Resolution of β5/LMP7 in the SDS gel is hampered as both subunits are of similar molecular weight and thus do not separate in our gels. Total protein staining was used as a loading control.",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(D) representative Western blots for the analysis of the cGAS/STING signaling pathway in PolgA+/+ and PolgAmut/mut cells with β-actin serving as loading control.",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(E) Secreted IFNβ in supernatants from three distinct PolgA+/+ and PolgAmut/mut cell lines. The 15.81 pg/ml detected by ELISA in PolgAmut/mut cell supernatants corresponds to 18.97 IU/ml recombinant mouse (rm) IFN-β according to the R&D Systems cytokine conversion table",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(F) RT-qPCR analysis of Stat1 in three different PolgA+/+ and three PolgAmut/mut cell lines.",
    "ncbi_link": "PolgA: 18975
Stat1: 20846"
  },
  {
    "caption": "(A) Western blot analysis of LMP2, LMP7, STAT1 and β-actin (loading control) in PolgA+/+ cells after incubation with either PolgA+/+ or PolgAmut/mut cell-conditioned medium for 48 h. Densitometric analysis of LMP2, LMP7 and STAT1 expression normalized to β-actin loading control set to 1 in PolgA+/+ incubated with either PolgA+/+ or PolgAmut/mut cell-conditioned medium from three different cell lines.",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(B) Western blot analysis of LMP2, LMP7, STAT1, and β-actin (loading control) upon siRNA-mediated silencing of cGAS or STING in PolgAmut/mut cells compared to untransfected (Ctrl) and non-sense scrambled transfection control (NC) in three independent experiments.",
    "ncbi_link": "cGAS: 214763
PolgA: 18975
STING: 72512"
  },
  {
    "caption": "(E) Western blot analysis of LMP2, LMP7, STAT1, and β-actin (loading control) in PolgA+/+ cells transfected with mouse wildtype mtDNA, mtDNA pretreated with DNase I or only DNase I for 48 h. Densitometric analysis of LMP2, LMP7 and STAT1 expression normalized to β-actin loading control in PolgA+/+ cells. Values are given as fold over PolgA+/+ control with the mean of normalized PolgA+/+ signal normalized to 1. (F) Western blot analysis of LMP2, LMP7, STAT1 and β-actin (loading control) in PolgA+/+ cells transfected with cGAMP for 24 h. Densitometric analysis of LMP2, LMP7 and STAT1 expression normalized to β-actin loading control (Ctrl) set to 1.",
    "ncbi_link": "PolgA: 18975
cGAMP: 72512"
  },
  {
    "caption": "(G) Protein expression of LMP2, LMP7 and β-actin (loading control) in wildtype (WT), cGAS KO or STINGgt/gt losss of function MEFs that had been transfected with 200 ng/ml mtDNA for 48 h.",
    "ncbi_link": "cGAS: 214763
STING: 72512"
  },
  {
    "caption": "(B) UTY-assay of CD8+ reporter T cells upon co-culture with different ratios of PolgA+/+ or PolgAmut/mut cells. Data are combined results of three independent experiments and normalized to the signal of maximum induction of PolgA+/+ cells in co-culture with CD8+ reporter T cells.",
    "ncbi_link": "PolgA: 18975"
  },
  {
    "caption": "(E) UTY-assay of CD8+ reporter T cells upon 1:2 co-culture (splenocytes:T cells) with splenocytes isolated from either WT or LMP7 KO mice and transfected with mtDNA. Splenocytes were isolated from 4 mice each in two different preparations.",
    "ncbi_link": "LMP7: 16913"
  },
  {
    "caption": "(A) Western blot analysis of the immunoproteasome subunits LMP2 and LMP7 in wild type (WT), cGAS KO and STINGgt/gt loss of function MEFs transfected with 1 μg/ml HT-DNA or plasmid-DNA for 48 h. β-actin was used as a loading control. Densitometric analysis of LMP2 and LMP7 expression normalized to β-actin loading control in wild type (WT) controls (ctrl) from three independent experiments.",
    "ncbi_link": "cGAS: 214763
STING: 72512"
  },
  {
    "caption": "(B) UTY-assay of CD8+ reporter T cells upon 1:2 co-culture (splenocytes:T cells) with splenocytes isolated from either wildtype (WT) or LMP7 KO mice and transfected with htDNA. Splenocytes were isolated from 4 mice each in two different preparations.",
    "ncbi_link": "LMP7: 16913"
  },
  {
    "caption": "(C) Western blot analysis of immunoproteasome subunits LMP2 and LMP7 in wild type (WT), heterozygous STAT1 mutated (STAT1*+/-) and homozygous STAT1 mutated (STAT1*-/-) skin fibroblasts transfected with 1 μg/ml HT-DNA or pretreated HT-DNA with DNase I for 48 h.",
    "ncbi_link": "STAT1: 6772"
  },
  {
    "caption": "Senescence-associated β-galactosidase (SA-β-gal) staining in A549, HAFF, HepG2 and H1299 cells after 48h transduction with either negative control lentiviruses (shCtrl) or those targeting GUARDIN (shGUARDIN). The graph shows percentage of SA-β-gal-positive cells.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Senescence-associated heterochromatin foci formation (SAHF) in A549 cells with either shCtrl or shGUARDIN. Representative IF staining with H3K9me3 antibodies (green) and nuclear Hoechst counterstaining (blue).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Secretion of SASP factors IL-6 and IL-8 in A549 cells with either shCtrl or shGUARDIN.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Western blotting for p21, p16 and p15 in HepG2 cells after 48h transduction with shCtrl or shGUARDIN-1, -2, respectively (left). Knockdown efficiencies analyzed by qPCR (right).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "SA-β-gal staining in A549 cells after 24h transduction with either shCtrl or shGUARDIN in combination with p21 shRNA (shp21). The graph shows percentage of SA-β-gal-positive cells.",
    "ncbi_link": "GUARDIN: 
p21: 1026"
  },
  {
    "caption": "qPCR measurement of p21 mRNA in A549, HepG2, HAFF and H1299 cells with either GUARDIN shRNA knockdown (top) or GUARDIN overexpression (bottom).",
    "ncbi_link": "GUARDIN: 
p21: 1026"
  },
  {
    "caption": "Western blotting for p53 and p21 in A549, HepG2, HAFF and H1299 cells with either GUARDIN shRNA knockdown (top) or GUARDIN overexpression (bottom).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "qPCR assays of NOXA, TIGAR, BAX and p21 mRNA levels in A549 cells with either shCtrl or shGUARDIN.",
    "ncbi_link": "GUARDIN: 
BAX: 581
p21: 1026
NOXA: 5366
TIGAR: 57103"
  },
  {
    "caption": "SDS-PAGE of RNA pulldown assays using biotin-labelled sense/antisense probes against GUARDIN from whole-cell lysates of A549 cells indicating putative GUARDIN-binding proteins (left); protein identities with high probabilities were determined by mass spectrometry (right).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "RNA pulldown assays interrogating putative GUARDIN-associated proteins identified in (A) from whole-cell lysates of A549 and HAFF cells. BRCA1, BARD1 served as positive controls and β-actin served as negative controls.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Subcellular localization of GUARDIN and its co-localization with LRP130. RNA FISH for GUARDIN (red) and IF for LRP130 (green) in A549 cells with either shCtrl or shGUARDIN. Nucleus were counterstained with Hoechst (blue).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "RNA pulldown assays using biotin-labelled sense/antisense probes against GUARDIN from whole-cell lysates of A549 cells. GUARDIN levels were measured by RT-PCR and co-precipitated LRP130 and PGC1α detected by Western blotting. BRCA1 and β-actin served as positive and negative controls, respectively.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "RIP assay using IgG/PGC1α antibodies from whole-cell lysates of A549 cells. GUARDIN, LRP130 and PGC1α levels were measured as per (E).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Two-step IP assays in whole-cell lysates of A549 cells transfected with FLAG-tagged PGC1α. First phase IPs were conducted with FLAG antibodies (left) and following elution with FLAG peptides, eluates were further subjected to second phase IPs with LRP130 antibodies (right). Samples were subjected to Western blotting and qPCR analysis for LRP130, PGC1α and GUARDIN, respectively.",
    "ncbi_link": "FLAG: 
GUARDIN: 
PGC1α: 10891"
  },
  {
    "caption": "Co-immunoprecipitation (co-IP) between LRP130 and PGC1α in A549 cells after 48h transduction with shCtrl or shGUARDIN. LRP130 was precipitated and samples subjected to Western blotting analysis for LRP130, PGC1α and β-actin as loading control.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Mammalian two-hybrid assays between pACT-LRP130 and pBIND-PGC1α in A549 cells after 48h transduction with shCtrl or shGUARDIN. Samples were subjected to the luciferase activity assays.",
    "ncbi_link": "GUARDIN: 
LRP130: 10128
PGC1α: 10891"
  },
  {
    "caption": "LRP130/PGC1α and p21 protein expression was measured by Western blot in A549 and HAFF cells after 48h transduction with shCtrl or shLRP130 (top left) or shPGC1α (bottom left) as indicated. qPCR assays for p21 mRNA levels were performed in parallel (right panels).",
    "ncbi_link": "p21: 1026
LRP130: 10128
PGC1α: 10891"
  },
  {
    "caption": "Western blotting analysis of LRP130, PGC1α and p21 protein levels in HAFF and A549 cells after 48h transduction with shCtrl or shGUARDIN.",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "ChIP assays detecting binding of LRP130/PGC1α to the p21 promoter using qPCR and RT-PCR (top left and right, respectively). IgG and p53 served as a negative and positive controls, respectively. Schematic illustrations of the putative LRP130/PGC1α binding sites within DNase I hypersensitive regions of the p21 promoter (bottom).",
    "ncbi_link": "p21: 1026"
  },
  {
    "caption": "qPCR assays for GUARDIN, FOXO1, FOXO3a and FOXO4 in A549 cells after 24h transduction with shCtrl or shGUARDIN.",
    "ncbi_link": "GUARDIN: 
FOXO1: 2308
FOXO3a: 2309
FOXO4: 4303"
  },
  {
    "caption": "Western blotting assays for FOXO4 and p21 protein expression in A549 cells after 48h transduction with shCtrl or shGUARDIN alone or in combination with shFOXO4. β-actin served as loading control.",
    "ncbi_link": "GUARDIN: 
β-actin: 
FOXO4: 4303"
  },
  {
    "caption": "Half-life times of FOXO4 mRNA in A549 cells with shCtrl or shGUARDIN measured by qPCR after treating cells with 5 μg/ml of actinomycin (ActD) for the indicated times.",
    "ncbi_link": "GUARDIN: 
FOXO4: 4303"
  },
  {
    "caption": "ChIP assays detecting binding of LRP130/PGC1α to putative binding sites in the FOXO4 promoter using qPCR (top). Data were normalized to the IgG negative control. Schematic illustration of the LRP130/PGC1α binding sites within DNase I hypersensitive regions of the FOXO4 promoter (bottom).",
    "ncbi_link": "FOXO4: 4303"
  },
  {
    "caption": "Luciferase assays conducted in A549 cells transfected with LRP130 or PGC1α using the pGL3 (negative control) or pGL3-FOXO4 promoter reporter plasmids.",
    "ncbi_link": "FOXO4: 4303
LRP130: 10128
PGC1α: 10891"
  },
  {
    "caption": "qPCR assays for LRP130 and FOXO4 mRNA levels (upper) and Western blotting analysis for LRP130 protein level (lower) in A549 cells after 48h transduction with LRP130 overexpression or knockdown.",
    "ncbi_link": "FOXO4: 4303
LRP130: 10128"
  },
  {
    "caption": "qPCR assays for PGC1α and FOXO4 mRNA level (upper) and Western blotting analysis for PGC1α protein level (lower) in A549 cells after 48h transduction with PGC1α overexpression or knockdown.",
    "ncbi_link": "FOXO4: 4303
PGC1α: 10891"
  },
  {
    "caption": "Luciferase activity assays in A549 cells transduced with shCtrl or shGUARDIN using the pGL3 (negative control) or pGL3-FOXO4 promoter reporter plasmids.",
    "ncbi_link": "GUARDIN: 
FOXO4: 4303"
  },
  {
    "caption": "qPCR assays for GUARDIN expression in A549 cells treated with increasing doses rapamycin for 24h",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "qPCR assays for GUARDIN expression in A549 cells treated with 100nM of rapamycin for the indicated times (B).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "A549 cells with shCtrl or shGUARDIN were treated with 100nM rapamycin or DMSO vehicle in the indicated combinations for 48h. Western blotting was used to measure p21 levels (left) while conducting SA-β-gal staining in parallel (middle) with the percentage of senescent cells calculated from the SA-β-gal staining (right).",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "Mammalian two-hybrid assays between pACT-LRP130 and pBIND-PGC1α in A549 cells treated with DMSO or 100nM rapamycin. Samples were subjected to the luciferase activity assays.",
    "ncbi_link": "LRP130: 10128
PGC1α: 10891"
  },
  {
    "caption": "SIX4 and FOSL2 mRNA (left) and protein levels (right) measured by qPCR and Western blotting, respectively in A549 cells treated with DMSO or 100nM rapamycin. TBP served as a control.",
    "ncbi_link": "FOSL2: 2355
SIX4: 51804"
  },
  {
    "caption": "qPCR (upper) and Western blotting (lower) assays for GUARDIN, SIX4 and FOSL2 expression in A549 cells comparing shCtrl with shSIX4 (left), shFOSL2 (middle) or FOSL2 (right) after transduction for 48h.",
    "ncbi_link": "GUARDIN: 
FOSL2: 2355
SIX4: 51804"
  },
  {
    "caption": "Luciferase assays in A549 cells transduced with shCtrl, shSIX4 or shFOSL2 using pGL3 (negative control) or pGL3-FOXO4 promoter reporter plasmids.",
    "ncbi_link": "FOSL2: 2355
FOXO4: 4303
SIX4: 51804"
  },
  {
    "caption": "ChIP assays comparing control IgG versus FOSL2 antibodies demonstrate specific recovery of the GUARDIN promoter by RT-PCR assay. UPe and UPk served as a positive and negative controls, respectively [54].",
    "ncbi_link": "GUARDIN: "
  },
  {
    "caption": "(c) qrtPCR of MCU, MCUR1 and MICU1 mRNA from mouse tissues (n = 3; mean ± s.e.m.).",
    "ncbi_link": "MCU: 215999
MCUR1: 76137
MICU1: 216001"
  },
  {
    "caption": "(d) qrtPCR of MCUR1 mRNA from HEK293T cell clones (n = 3; mean ± s.e.m.). KD, knockdown. Neg shRNA, negative shRNA.",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(e) qrtPCR of MCUR1 mRNA from HeLa cell clones and of rescued MCUR1 mRNA levels in shHe2 clone cells (n = 3; mean ± s.e.m.). The same lentiviral shRNAs were used to generate shHK4 and shHe1 and shHK5 and shHe2, respectively.",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(f) MCUR1 protein expression levels (top) and densitometric analysis (bottom left) (n = 3; ± s.e.m.). Bottom right, Flag-tagged MCUR1 protein expression in clone shHe2 cells reconstituted with shRNA-resistant MCUR1 cDNA plasmid. WB, western blot.",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(i-p) Cytoplasmic (green) and mitochondrial matrix (red) [Ca2+] responses in HeLa (m-p) cells challenged with ionomycin or histamine (100 μM), respectively. (n = 3). (m) HeLa cells expressing negative shRNA. (n) Clone shHe2. (o) Clone shHe2 re-expressing MCUR1 (n = 3). (p) Quantification of peak rhod-2 fluorescence. *P0.05, **P0.01 (mean±s.e.m.).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(q) [Ca2+]c and [Ca2+]m signals evoked by ATP (100 μM) and thapsigargin (Tg, 2 μM) were monitored simultaneously using fura-2/AM and mitopericam (ipcam490), respectively in control (left) and MCUR1-knockdown (right) HeLa cells. [Ca2+]c is calibrated in nanomolar concentrations (black), whereas mitopericam fluorescence is inversely normalized to baseline (F0/F; red).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(r) Summary mean [Ca2+]c and [Ca2+]m peaks during ATP stimulation (negative shRNA n = 29; MCUR1 knockdown n = 36 cells). *P0.05 (mean±s.e.m.).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "Digitonin-permeabilized HeLa cells bathed in intracellular-like solution containing thapsigargin (Tg) were loaded with the ΔΨm indicator JC-1 and the Ca2+ indicator Fura2FF, to which pulses of 10 μM Ca2+ were added before the addition of the mitochondrial uncoupler CCCP (carbonyl cyanide m-chloro phenyl hydrazone). (a-e) Representative traces from three independent experiments depict simultaneous changes of bath [Ca2+] and ΔΨm in cells expressing negative shRNA (Neg shRNA; a), clone shHe1 (b), clone shHe2 (c), clone shHe2 re-expressing MCUR1 (d) and HeLa cells stably overexpressing MCUR1 (e). Under similar conditions, 1 μM Ru360 was added before 10 μM Ca2+ pulses until the addition of CCCP.",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(f-i) Representative traces from three independent experiments depict simultaneous changes of bath [Ca2+] and ΔΨm in negative shRNA cells (f), MCUR1-knockdown clone shHe1 (g) and shHe2 (h), and in control cells overexpressing MCUR1 (i).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(j,k) Negative shRNA (j) and MCUR1-overexpressing (k) HEK293T cells were permeabilized with digitonin in intracellular-like medium containing thapsigargin and bath [Ca2+] indicator Fura2FF, and then pulsed with 10 μM Ca2+. After mitochondrial clearance of bath Ca2+, Ru360 caused an elevation of bath [Ca2+], indicating that steady-state bath [Ca2+] after the pulse was maintained by a balance of MCU-mediated Ca2+ uptake and CGP37157 (10 μM)-sensitive Na+-Ca2+ exchanger-mediated extrusion. CCCP was added as indicated. The solid line is the mean; shaded areas are ±s.e.m. (n = 3).",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(a,b) Confocal images of HeLa cells transiently co-transfected for 48 h with GFP-tagged MCUR1 and DsRed-Mito plasmids (a) or mRFP-tagged MCUR1 and EYFP-Mito (b). Scale bar, 20 μm.",
    "ncbi_link": "Mito: 
MCUR1: 63933"
  },
  {
    "caption": "(d) Immunoblot analyses of mitochondria-containing pellet and cytosolic fractions from plasma-membrane-permeabilized HeLa cells. Permeabilized cells were treated with or without tBid (50 nM) for outer mitochondrial membrane permeabilization and the appearance of cytosolic cytochrome c was verified. Intact and outer mitochondrial membrane permeabilized samples were exposed to proteinase K for 10 min. These samples were probed using antibodies against HSP60, OXA1, Flag and MCUR1.",
    "ncbi_link": "Bid: 637
MCUR1: 63933"
  },
  {
    "caption": "(e) Reciprocal co-immunoprecipitation (IP) of MCU-GFP and MCUR1-Flag transiently expressed in COS7 cells. Representative of four independent experiments. WB, western blot.",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(f) Co-immunoprecipitation of MICU1-Flag with MCU-GFP but not with MCUR1-GFP transiently expressed in COS7 cells. Representative of four independent experiments.",
    "ncbi_link": "MCU: 90550
MCUR1: 63933
MICU1: 10367"
  },
  {
    "caption": "(g) Immunoprecipitation of LETM1-GFP with anti-LETM1 failed to pull down MCUR1-Flag in transiently transfected COS7 cells.",
    "ncbi_link": "LETM1: 3954
MCUR1: 63933"
  },
  {
    "caption": "(h) Immunoprecipitation with Flag antibody pulled down LETM1-Flag or MCU-Flag transiently expressed in COS7 cells (immunoprecipitation lanes 2 and 3, lower panel), but only co-immunoprecipitated MCUR1-V5 in the MCU-Flag-expressing cells (immunoprecipitation lanes 4 versus 5, upper panel), despite lower expression of MCU-Flag in MCUR1-co-transfected cells (compare MCU-Flag and LETM1-Flag expression in MCUR1-co-transfected cells in lysate lanes 4 and 5, bottom panel). Representative of three independent experiments. Uncropped images of blots/gels are shown in Supplementary Fig. S6.",
    "ncbi_link": "LETM1: 3954
MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(a) qrtPCR of MCU mRNA from wild-type and stable MCUR1-overexpressing HeLa cells that were transiently transfected with scrambled siRNA or siRNA against MCU. ***P0.001 (mean±s.e.m.).",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(b) [Ca2+]m responses to histamine (100 μM) in HeLa cells stably overexpressing MCUR1 and in cells transiently transfected with scrambled siRNA or MCU siRNA, and in stable MCUR1-overexpressing HeLa cells transfected with MCU siRNA. After 48 h of siRNA transfection, cells were loaded with rhod-2 and [Ca2+]m responses were visualized by confocal microscopy. Solid lines are mean; shaded regions are ±s.e.m.; n = 3. (c) Quantification of peak rhod-2 fluorescence following histamine stimulation. *P0.05, ***P0.001 (mean±s.e.m.; NS, not significant; n = 3).",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(d) qrtPCR of MCU mRNA from wild-type and MCUR1-knockdown HeLa cells that were transiently transfected with MCU cDNA. **P0.01, ***P0.001 (mean±s.e.m.; n = 3).",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(e) [Ca2+]m responses to histamine (100 μM) in wild-type and MCUR1 (shHe2)-knockdown HeLa cells overexpressing MCU. Negative shRNA (Neg shRNA) and MCUR1-shHe2 cells were used as controls. Solid lines are mean; shaded regions are ±s.e.m.; n = 3. (f) Quantification of peak rhod-2 fluorescence following histamine stimulation. ***P0.001 (mean±s.e.m.; n = 3).",
    "ncbi_link": "MCU: 90550
MCUR1: 63933"
  },
  {
    "caption": "(a) AMP/ATP ratios in stable HeLa cell lines stably expressing negative shRNA (Neg shRNA), MCUR1 shRNA (clone shHe2) or shHe2 with MCUR1 re-expressed. **P0.01 (mean±s.e.m.; n = 3).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(b) O2 consumption rates (OCR) in stable HeLa cells expressing irrelevant shRNA, clone shHe2, and clone shHe2 re-expressing MCUR1, exposed sequentially to oligomycin (i), FCCP (ii) and rotenone plus myzothiazol (iii).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "(d) Western blot of phosphorylated and total AMPK (top) and densitometric analysis (bottom) in stable HeLa lines expressing negative shRNA or MCUR1 shRNA (clone shHe2) and clone shHe2 re-expressing MCUR1. *P0.05, **P0.01 (mean±s.e.m.; n = 3). (e) Western blot of LC3 or tubulin in stable HeLa lines expressing negative shRNA or MCUR1 shRNA (clone shHe2) and clone shHe2 re-expressing MCUR1 (top) and quantification of LC3-II/(LC3-I + LC3-II) (bottom) expressed as fold increase over levels in cells expressing irrelevant shRNA. *P0.05, **P0.01 (mean±s.e.m.; n = 3).",
    "ncbi_link": "MCUR1: 63933"
  },
  {
    "caption": "Verification of screen hits by mtKeima-based FACS analysis of mitophagy. Upper: representative FACS analysis of mitophagy in HeLa cells expressing sgNTC and sgFBXL4. Bottom: quantitative analysis of mitophagy levels in HeLa cells expressing the indicated sgRNAs. The percentage of cells with high mitophagy level is indicated in red. Two independent sgRNAs were used for each gene. NTC: non-targeting control.",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "Imaging analysis of mitophagy levels in the indicated HeLa cells. Left: sequencing result of WT and FBXL4-KO cells and representative mitophagy images, white arrows point to mitolysosomes (FBXL4-KO cells were not labeled because of the large numbers of mitolysosomes); middle: percentage of cells with mitophagy (mitolysosome-positive); right: quantification of mitolysosome/mitochondria area. n: number of cells analyzed (middle); number of imaging areas (20-30 cells/area) analyzed (right).",
    "ncbi_link": "FBXL4: 26235"
  },
  {
    "caption": "Immunoblot analysis of the indicated HeLa cells. B: BNIP3; N: NIX. Two clones were shown for each double and triple knockout cells.",
    "ncbi_link": "BNIP3: 664
NIX: 665"
  },
  {
    "caption": "Determination of the submitochondrial localization of FBXL4 by Protease K and trypsin digestion. Mitochondria from HeLa FBXL4-FLAG stable line were purified and stored as intact mitochondria or treated with hypotonic swelling buffer or lysed with Triton X-100 buffer. Different mitochondrial preparations were then digested with Protease K or trypsin.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Analysis of the association of FBXL4 with membrane by alkaline carbonate extraction. Purified mitochondria from HeLa FBXL4-FLAG stable line were treated with alkaline carbonate buffer at the indicated pH and then centrifuged to collect the supernatant and the pellet fractions. S: supernatant; P: pellet.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Immunoprecipitation analysis of the FBXL4-Skp1-Cullin1 (SCF-FBXL4) complex. HeLa cells were infected with lentiviruses expressing the indicated genes. ∆F: the F-box deletion mutant of FBXL4-FLAG; 4A: FBXL4-4A mutant as shown in (A).",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Immunoprecipitation analysis of the ubiquitination of BNIP3. FLAG-BNIP3 (knockin), FBXL4-KO, HA-ubiquitin (Ub) HeLa cells were rescued with WT or ∆F FBXL4, and treated with DMSO or MG132 (20 μM) for 8 hours.   Immunoprecipitation analysis of the ubiquitination of NIX. FLAG-NIX (knockin), FBXL4-KO, HA-Ub HeLa cells were treated the same as (F).  ",
    "ncbi_link": "FLAG: 
HA: 
Ub: 
ubiquitin: 
BNIP3: 664
NIX: 665
FBXL4: 26235"
  },
  {
    "caption": "Immunoblot analysis of the indicated HeLa cells. FBXL4-KO HeLa cells were rescued with vector, FBXL4-FLAG, FBXL4(4A)-FLAG or FBXL4(∆F)-FLAG.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Immunoblot analysis of the indicated HeLa cells. WT and FBXL4-KO HeLa cells were rescued with vector, WT or mutant FBXL4-FLAG.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Immunoprecipitation analysis of FBXL4-substrate interaction. FBXL4-KO HeLa cells were rescued with vector, FBXL4(∆F)-FLAG or mutant FBXL4(∆F)-FLAG.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Immunoprecipitation analysis of the integrity of the SCF-FBXL4 complex. Upper: FBXL4-KO HeLa cells expressing vector, WT or mutant FBXL4-FLAG were crosslinked with DSP and subject to anti-FLAG immunoprecipitation; lower: quantification of the ratio of Cullin1/FLAG band intensities.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. (A) Effect of G-CSF and CoPP-induced mobilization in C57BL/6-Tg(UBC-GFP)30Sch/J donor mice (mean + individual values, one-way Anova with Bonferroni post-test, n = 16 mice per group): Donor mice treated with CoPP had the highest number of mobilized granulocytes (i) and KLS cells (ii), compared to control or G-CSF-treated donor mice",
    "ncbi_link": "GFP: 
UBC: 7316"
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. Recipient mice which were transplanted with CoPP-mobilized PBMC had the highest number of WBC, PLT and the highest hematocrit values 2 weeks after PBMC transplantation, compared to G-CSF-mobilized and control PBMC recipients (mean + individual values, one-way Anova with Bonferroni post-test, NaCl: n = 8, G-CSF: n = 7, CoPP: n = 9 mice per group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. Recipient mice which were transplanted with CoPP-mobilized PBMC had the highest chimerism among CD45+ cells, granulocytes and B cells 2, 4 and 18 weeks after transplantation. Chimerism among T cells was the highest in recipients of G-CSF-mobilized PBMC 2 weeks after transplantation, but 18 weeks after transplantation it was the highest in CoPP-mobilized PBMC recipients (mean + SEM, two-way Anova with Bonferroni post-test, NaCl: n = 8, G-CSF: n = 7, CoPP: n = 9 mice per group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. The majority of primary recipients transplanted with G-CSF and CoPP-mobilized PBMC have detectable GFP chimerism among BM KLS cells.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. Fraction of secondary recipient mice with chimerism in PB CD45+ cells exceeding 1% tends to be higher after CoPP-mobilized PBMC transplant than G-CSF-mobilized PBMC transplant.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. PB chimerism in secondary recipients is higher in CoPP group than in the control group (mean + individual values, Kruskal-Wallis test with Dunn's post-test, NaCl: n = 7, G-CSF: n = 6, CoPP: n = 8 mice per group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. Percentage of secondary recipient mice with GFP chimerism in BM KLS (G) and KLS-(H) cells higher that 1% is similar in G-CSF and CoPP groups.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Donor GFP+ mice were treated with NaCl, G-CSF or CoPP daily. At the 5th day of treatment we transplanted 5x106 of isolated PBMC to the lethally irradiated GFP- recipient mice, together with 105 GFP- BM-derived competitor cells. After 18 or 20 weeks we performed secondary transplantation of primary recipients' BM to lethally irradiated secondary recipients and followed the chimerism for additional 14 weeks. GFP chimerism in KLS (I) and KLS- (J) cells in the BM of secondary recipients (mean + individual values, Kruskal-Wallis test with Dunn's post-test, NaCl: n = 7, G-CSF: n = 6, CoPP: n = 8 mice per group).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "HO-1 deficient and control C57BL/6xFVB mice were injected with CoPP three times, every second day and sacrificed 24 hours after last injection. Total leukocyte counts in PB (HO-1+/+: n = 5, HO-1-/- DMSO: n = 6, HO-1-/- CoPP: n = 4 mice per group). Granulocyte percentage among PB leukocytes.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "HO-1 deficient and control C57BL/6xFVB mice were injected with CoPP three times, every second day and sacrificed 24 hours after last injection. Cytokine and growth factor concentrations in plasma (E - HO-1+/+ n = 5, HO-1-/- DMSO: n = 5, HO-1-/- CoPP: n = 3 mice per group). Results are shown as mean + SEM, two-way Anova with Bonferroni post-test.",
    "ncbi_link": "HO-1: 15368"
  },
  {
    "caption": "Nrf2-deficient and control C57BL/6 mice were injected with CoPP daily for 5 days and sacrificed 6 hours after last injection (DMSO: n = 4, CoPP: n = 5 mice per group). CD45+ cell numbers in PB measured by flow cytometry. Granulocyte percentage among PB leukocytes.",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "Nrf2-deficient and control C57BL/6 mice were injected with CoPP daily for 5 days and sacrificed 6 hours after last injection (DMSO: n = 4, CoPP: n = 5 mice per group). Cytokine and growth factor concentrations in plasma",
    "ncbi_link": "Nrf2: 18024"
  },
  {
    "caption": "(A, B) The mRNA levels of aub (A) and vasa (B) were quantified upon the depletion (RNAi) of L(3)mbt, Lint-1, CoRest, E2F2, Myb, Mip120, and Mip130, and were compared with those in normal OSCs (control). Data represent the means ± SE (n = 3 biological replicates). The p values were calculated with the t-test. *p: < 0.05, **p: < 0.01. All t-tests were performed against samples with⎾ symbol.",
    "ncbi_link": "aub: 34524
CoRest: 32941
E2F2: 35381
L(3)mbt: 43288
Lint-1: 32055
Mip120: 36499
Mip130: 31153
Myb: 32543
vasa: 26067080"
  },
  {
    "caption": "(C) Proteins immunoprecipitated  with the anti-L(3)mbt antibody from the OSC   lysates before (control) and after L(3)mbt knockdown (KD) were silver-stained. The bands corresponding to  L(3)mbt-L and L(3)mbt-S are indicated.",
    "ncbi_link": "L(3)mbt: 43288"
  },
  {
    "caption": "(F, G) The mRNA levels of vasa (F) and aub (G) were quantified upon the depletion (RNAi) of L(3)mbt, Atac3, Prod, CG2662/Lint-O, and CG2199, and were compared with those in normal OSCs (control). Data represent the means ± SE (n = 3 biological replicates). The p values were calculated with the t-test. **p: < 0.01. All t-tests were performed against samples with⎾ symbol.",
    "ncbi_link": "Atac3: 38055
aub: 34524
CG2199: 38159
CG2662: 31254
Lint-O: 31254
L(3)mbt: 43288
Prod: 37187
vasa: 26067080"
  },
  {
    "caption": "(B) Immunoprecipitation  (IP)/western blotting shows that WT  Lint-O, but not its ∆SAM mutant co-immunoprecipitated  with L(3)mbt from the OSC  lysates. n.i.: non-immune IgG.",
    "ncbi_link": "Lint-O: 31254"
  },
  {
    "caption": "(F, G) The mRNA levels of vasa (F) and aub (G) were quantified upon ectopic expression of EGFP, as well as WT Lint-O and its ∆SAM and 8CA mutants (Fig EV3A), in Lint-O-lacking OSCs (Lint-O RNAi) and were compared with those in normal OSCs (control). Data represent the means ± SE (n = 3 biological replicates). The p values were calculated with the t-test. *p: < 0.05. All t-tests were performed against samples with⎾ symbol.",
    "ncbi_link": "EGFP: 
aub: 34524
Lint-O: 31254
vasa: 26067080"
  },
  {
    "caption": "(J) ChIP-qPCR shows that L(3)mbt binding to the vasa promoter was weakened after the loss of Lint-O. Data represent the means ± SE (n = 3 biological replicates). The p values were calculated with the t-test. **p: < 0.01. All t-tests were performed against samples with⎾ symbol.",
    "ncbi_link": "Lint-O: 31254
vasa: 26067080"
  },
  {
    "caption": "(K) Western blotting showing the amounts of L(3)mbt, Lint-O, and  histone H3 (H3) in normal (control), L(3)mbt-depleted (RNAi), and  Lint-O-depleted (RNAi) OSCs.",
    "ncbi_link": "Lint-O: 31254
L(3)mbt: 43288"
  },
  {
    "caption": "(L) The lint-O mRNA levels in normal (control), L(3)mbt-depleted (RNAi), and Lint-O-depleted (RNAi) OSCs are shown by fragments per kilobase million (FPKM). Data represent the means ± SE (n = 3 biological replicates). The p values were calculated with the t-test. *p: < 0.05, **p: < 0.01. All t-tests were performed against samples with⎾ symbol.",
    "ncbi_link": "lint-O: 31254
Lint-O: 31254
L(3)mbt: 43288"
  },
  {
    "caption": "(B) RT-qPCR analysis shows the mRNA levels of lint-O in y w and Lint-OKO ovaries. Data are expressed as mean and error bars represent SD. n = 2 biological replicates.",
    "ncbi_link": "lint-O: 31254
Lint-O: 31254"
  },
  {
    "caption": "(D) Confocal images of y w and Lint-OKO ovaries immunostained for Vasa. Scale bar: 50 μm.",
    "ncbi_link": "Lint-O: 31254"
  },
  {
    "caption": "(E) Confocal images of y w and Lint-OKO ovarioles immunostained for Vasa. Vasa was ectopically expressed in follicle cells (white arrowheads). Scale bar: 50 μm.",
    "ncbi_link": "Lint-O: 31254"
  },
  {
    "caption": "(A) Western blotting  shows that Vasa, Piwi, and Aub  were ectopically expressed in Lint-OKO and  L(3)mbtts1 larval brains  at 29ºC. Anti-Lint-O, anti-L(3)mbt, anti-Vasa, andi-Piwi, anti-Aub, and anti-Tubulin  antibodies were used.",
    "ncbi_link": "Lint-O: 31254
L(3)mbt: 43288"
  },
  {
    "caption": "(B) Confocal images of y w, Lint-OKO, and L(3)mbtts1 immunostained for Vasa (magenta), MIRA (green), and ELAV (green). Scale bar: 100 μm.",
    "ncbi_link": "Lint-O: 31254
L(3)mbt: 43288"
  },
  {
    "caption": "(C) Quantification of brain lobe volume for the following genotypes: Lint-OKO -/+ (n = 42 biological replicates), Lint-OKO -/- (n = 36 biological replicates), and L(3)mbtts1 -/- (n = 34 biological replicates). Boxplot central bands, upper edges of boxes, lower edges of boxes, upper whiskers and lower whiskers show median, third quartile, first quartile, maxima, and minima, respectively. P-values were calculated by the Student's t-test. (***P-value < 0.001).",
    "ncbi_link": "Lint-O: 31254
L(3)mbt: 43288"
  },
  {
    "caption": "(D, E) The genomic regions harboring the vasa (D) and aub (E) genes. The RNA-seq reads in y w, L(3)mbtts1, and Lint-OKO brains are shown. The shading in gray corresponds to exons. The y-axis shows the number of RPM. RNA-seq samples were biological triplicates.",
    "ncbi_link": "aub: 34524
Lint-O: 31254
L(3)mbt: 43288
vasa: 26067080"
  },
  {
    "caption": "F. Relative fluorescence GFP intensities in the nucleus and cytoplasm of wild type, KAP114 knockout strains, and KAP114 knockout strains rescued by KAP114 deletion mutants.",
    "ncbi_link": "KAP114: 852610"
  },
  {
    "caption": "A. Wild type and KAP114 knockout strains were diluted serially and spotted onto YPD plates in the presence of 1.5 M NaCl.",
    "ncbi_link": "KAP114: 852610"
  },
  {
    "caption": "B. The KAP114 knockout strain was transformed with vector control (lane 2) and a plasmid containing wild type KAP114, KAP114 (Δ347-371), or KAP114 (Δ899-956) (lanes 3-5). Wild type and KAP114 knockout strains containing plasmids were serially diluted and grown in minimal medium plates supplemented with 1.5 M NaCl. Growth temperatures are indicated.",
    "ncbi_link": "KAP114: 852610"
  },
  {
    "caption": "C. A heatmap generated by three independent biological replicates shows gene expression profiles of wild type and KAP114 knockout strains grown in the presence of 1.5 M NaCl. The Log2 (fold-change) values and the color scale are shown.",
    "ncbi_link": "KAP114: 852610"
  },
  {
    "caption": "E, F. (E) qPCR analysis of gene expression in the KAP114 knockout strains (green bars) compared to wild type (black bars) under regular conditions. (F) qPCR analysis of gene expression in the KAP114 knockout strain (green bars) compared to wild type (black bars) grown in high salt conditions. qPCR fold-changes in mRNA expression are relative to control (YPD media, black bars). Actin was used as the internal control.",
    "ncbi_link": "Actin: 
KAP114: 852610"
  },
  {
    "caption": "G. ChIP-qPCR assays showing yTBP-GFP binding to the promoter of indicated genes in wild type and KAP114 knockout strains grown in high salt conditions (light green bars) compared to under regular conditions (black bars). Chip-qPCR fold-enrichment is relative to control (YPD media, black bars).",
    "ncbi_link": "KAP114: 852610"
  },
  {
    "caption": "E, F) Boxplot comparing the distribution of the Dmd and Prune2 genes in the WT, mdx, mdx++ and mdx+- mice groups. The central band of the boxplot denotes the median; the box denotes the first and third quartile; the whiskers are computed as min(max(x), Q3 + 1.5 IQR) and max(min(x), Q1 - 1.5 * IQR), where min(x) and max(x) denote the minimum and maximum of the distribution, Q1 and Q3 the first and third quartile, and IQR the interquartile range.",
    "ncbi_link": "Dmd: 13405
Prune2: 353211"
  },
  {
    "caption": "D) Trajectory plots comparing the trajectories of Chordc1 and Psat1 in WT and mdx mice.",
    "ncbi_link": "Chordc1: 66917
Psat1: 107272"
  },
  {
    "caption": "E) Trajectory plots comparing the trajectories of Cd59a, Chordc1, Hpgd, Ldhb, Lincred1, Myo6, Slc39a11 and Tlr1 in WT, mdx++ and mdx+- mice.",
    "ncbi_link": "Cd59a: 12509
Chordc1: 66917
Hpgd: 15446
Ldhb: 16832
Lincred1: 100996933
Myo6: 17920
Slc39a11: 69806
Tlr1: 21897"
  },
  {
    "caption": "C Hemizygous  K18-hACE2 mice  were treated intranasally with 20 µg of NM1251 (n = 15) or NM1267 (n = 12) seven hours prior to infection with 3*103 PFU SARS-CoV-2 B.1.  survival were monitored for 14 days. , ****P < 0.0001, by log-rank test",
    "ncbi_link": "ACE2: 59272
K18: 3875"
  },
  {
    "caption": "B, Hemizygous K18-hACE2 mice were treated intranasally with 20 µg of NM1251 (n = 8), NM1267 (n = 9) or  NM1268 (n = 9) seven hours prior to infection with 3*103 PFU SARS-CoV-2 B.1.617.2 (Delta).  Weight loss were monitored for 14 days. Dashed line indicates humane endpoint and symbols represent mean ± SEM ****P < 0.0001 in orange between NM1251  and NM1267  and in purple between  NM1251 and  NM1268, *P < 0.1 in black between  NM1267  and NM1268, by two-way ANOVA with Sidak's multiple comparison test",
    "ncbi_link": "ACE2: 59272
K18: 3875"
  },
  {
    "caption": "C Hemizygous K18-hACE2 mice  were treated intranasally with 20 µg of NM1251 (n = 8), NM1267  (n = 9) or  NM1268 (n = 9) seven hours prior to infection with 3*103 PFU SARS-CoV-2 B.1.617.2  (Delta). survival were monitored for 14 days. ***P < 0.001 in orange between NM1251 and NM1267 and ****P < 0.0001 in purple between NM1251 and  NM1268, by log-rank test",
    "ncbi_link": "ACE2: 59272
K18: 3875"
  },
  {
    "caption": "Two top-ranked SplashRNA-designed shRNAmirs targeting human Nurd complex components and a control shRNAmir targeting human CD4 were cloned into both miR-AB  and  miR-E lentiviral vectors with Venus as reporter. The  lentiviruses packaged by these constructs were used for transduction of multiple human cell lines. RNAi efficiency was determined by  western blot  (WB) analysis of target protein levels in the lysates of the transduced cells. -actin served as loading control.",
    "ncbi_link": "miR-AB: 
miR-E: 
Venus: 
CD4: 920"
  },
  {
    "caption": "The  RNAi  efficiency of  Pten.1524 and Pten.932 shRNAmir mediated by  miR-AB vs. miR-E was tested in NIH-3T3 cells in the context of <30% transduction efficiency (GFP as reporter). Representative western blots of Pten protein expression of the  FACS-sorted  GFP+ cells from two biological replicates were shown. β-actin served as loading control.",
    "ncbi_link": "GFP: 
miR-AB: 
miR-E: 
Pten: 19211"
  },
  {
    "caption": "Two top-ranked SplashRNA-designed shRNAmirs targeting  human or  mouse surface protein  FAS  were cloned into Venus-expressing  miR-AB lentiviral  vectors which harbor different promoters to drive the shRNAmir expression. The packaged  lentiviruses were used to infect the indicated human or mouse cell lines. A shRNAmir targeting human or mouse CD4 driven under hCMV  promoter was used as control. After >96h of infection,  FAS  protein levels in the transduced  Venus-positive cells were determined by surface  staining and shown in histograms (top panels) and quantified by MFI of  APC (bottom panels).",
    "ncbi_link": "miR-AB: 
Venus: 
CD4: 12504"
  },
  {
    "caption": "293T cells were co-transduced with four  miR-AB lentiviruses  at 1:1 ratio, which carries a neutral shRNAmir targeting CD4 or CD19, with Azurite, GFP, Ametrine or mOrange as reporter respectively. Cells were cultured for 22 days and fluorescence positive cells were quantified at the time points as indicated. Representative contour FACS  plots cells on day 4 and day 22 shown (top panels). Cell numbers of untransduced, single fluorescence positive cells and quadruple positive cells were quantified and normalized to untransduced cells on day 4, and plotted over time (bottom panel). Data are shown as mean ± s.d. and n=4. NS indicates no significant difference (P>0.05, two-tailed unpaired Student's t-test).",
    "ncbi_link": "GFP: 
miR-AB: 
CD19: 930
CD4: 920"
  },
  {
    "caption": "CD8+ T cells were activated for 16h and then co-transduced with  miR-AB retroviruses at 1:1 ratio, which carries a SplashRNA-designed shRNAmir, targeting surface protein CD127,  CD90, CD44  or  CD8, with  Azurite, GFP,  Ametrine or mCherry2 as fluorescent reporters respectively for 4h. miR-AB retroviruses  expressing CD19-specific shRNAmirs with same fluorescent reporters were used as controls. Surface staining was performed 72h after transduction. FACS data were shown as overlaid histograms of control shRNAmirs (shCD19s) and target shRNAmirs (shCD127, shCD90, shCD44 or shCD8). Cells were categorized as sixteen populations expressing single, double, triple or quadruple fluorescent proteins or not (none) and fluorescent reporter-positive plots were highlighted with thick frames and white background. Each population's surface  staining   profile was shown on the right. The data was representative of two biologically independent experiments.",
    "ncbi_link": "miR-AB: 
CD19: 12478
CD44: 12505
CD8: 12526///12525
CD127: 16197
CD90: 21838"
  },
  {
    "caption": "(a) Western blot analysis of CALM, actin, GAPDH and LC3-II in several cell lines (HeLa, HEK, CAD and murine embryonic fibroblast (MEF)) where CALM was knocked down using shRNA or siRNA, as indicated, or knockout with rescue experiment. In all experiments in this paper, we used a scramble siRNA or a luciferase shRNA as controls. The cells were starved in Hanks balanced salt solution (HBSS) and treated with Baf A1 as indicated. (BC, basal conditions; SE, short exposure; LE, longer exposure). Quantification of LC3-II/actin or GAPDH ratio is shown in Supplementary Fig. 1A. *Not specific.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(b) LC3 dot counting in CALM knockdown cells. CALM was knocked down in HeLa cells expressing GFP-LC3 and with or without an siRNA-resistant form of wild-type CALM (rescue), as indicated. The cells were starved in HBSS for 4 h, fixed and subjected to fluorescence microscopy to score the number of LC3 dots per cell. The knockdown efficiency and the level of the siRNA-resistant form of CALM are shown on the left on the western blotting. The number of LC3 dots per cell (shown as mean ±s.d.) is shown on the graph for each condition (n≥300 cells per condition; BC, basal conditions). The ratio of the number of LC3 dots per cell between starvation and basal conditions is shown on the right (*P0.01; NS, not significant, two-tailed t-test). Pictures obtained from automated microscope are shown. Scale bars, 20 μm.",
    "ncbi_link": "LC3: 440738///81631///84557
CALM: 8301"
  },
  {
    "caption": "(a) p62 vesicle formation in CALM knockdown HeLa cells. Confocal pictures are shown. #CALM-downregulated cells where p62 vesicles accumulate. Data are representative of three independent experiments and shown as mean ±s.e.m. (n≥500 cells; *P0.01; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(b) Western blot analysis of p62, actin and GAPDH in HeLa cells and HEK cells (basal conditions, BC, or without serum for 1 h) where CALM was knocked down using shRNA or siRNA, as indicated. Data are mean ±s.d (n=3 experiments for HeLa cells and HEK cells; *P0.05; two-tailed t-test).",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(c) Percentage of huntingtinQ74-expressing cells with aggregates in CALM knockdown HeLa cells. Data depict one representative experiments performed in triplicate, out of three independent experiments and shown as mean ±s.d. (*P0.05; two-tailed t-test).",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(d) Tau-positive tangle formation in CALM knockdown cells. HeLa cells transiently expressing DsRed-tau 4R were treated with Baf A1 for 4 h as indicated. Cells were fixed and analysed by confocal microscopy after immnunostaining for phosphorylated tau using PHF1 antibody (green). Data represent the number of cells with phosphorylated tau-positive tangles as mean ±s.e.m. (n=3 experiments; *P0.01; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "tau: 4137
CALM: 8301"
  },
  {
    "caption": "(b) Western blot analysis of p62, actin and GAPDH in HeLa cells and HEK cells (basal conditions, BC, or without serum for 1 h) where CALM was knocked down using shRNA or siRNA, as indicated. Data are mean ±s.d (n=3 experiments for HeLa cells and HEK cells; *P0.05; two-tailed t-test).",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(a) Formation of endogenous ATG12 vesicles in CALM knockdown HeLa cells in basal (BC) and serum starvation conditions. Confocal pictures are shown with arrows indicating ATG12 vesicles in starvation conditions. Data are from one representative experiment, out of three independent experiments. Data shown as mean ±s.e.m. (n≥500 cells; *P0.01; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(b) Co-localization between GFP-ATG16L1 and internalized cholera toxin subunit B conjugated with Alexa555 (CTX; 20 min) in CALM knockdown HeLa cells. Confocal pictures are presented with magnified areas showing the co-localization between ATG16L1 and CTX in greater detail. Scale bars, 5 μm. The Pearson's coefficient between ATG16L1 and cholera toxin is shown. Data are representative of three independent experiments and shown as mean ±s.d. (n≥20 cells; *P0.05; two-tailed t-test).",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(c) Size of endogenous ATG12 vesicles in CALM knockdown HeLa cells in starvation conditions. Confocal pictures are shown with arrows indicating ATG12 vesicles and # indicating CALM knockdown cells. Data are representative of three independent experiments and shown as mean ±s.d. (n≥100 vesicles; *P0.05; two-tailed t-test). (AU, arbitrary unit). Scale bars, 5 μm.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(d) Live-cell imaging of ATG16L1-GFP in CALM knockdown HeLa cells. ATG16L1 pictures from various time points of a 5-min movie are shown in inverted grey style. Arrows indicate ATG16L1 vesicles. The number of fusion events per 5 min is shown. Data are representative of five movies and shown as mean ±s.d. (*P0.05; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(e) In vitro fusion assay of post-nuclear supernatant from HeLa cells expressing either GFP-ATG16L1 or mStrawberry-ATG16L1 in control and CALM knockdown conditions. Confocal pictures are shown where ATG16L1-mStrawberry signal is shown in purple to enable better visualization. Fused vesicles appear in white. The ATP-negative condition, which prevents SNARE-dependent fusion, is also shown as a control for the reaction. Magnified areas are shown to allow visualization of the vesicles. The percentage of fused vesicles is represented. n=numbers of vesicles scored per field (a minimum of five fields were analysed per condition). Data are representative of two independent experiments and shown as mean ±s.d. (n≥100 vesicles). Scale bars, 5 μm. (*P0.05; two-tailed t-test).",
    "ncbi_link": "ATG16L1: 55054
CALM: 8301"
  },
  {
    "caption": "(a) LC3 levels in CALM knockdown cells. CALM was knocked down in cells expressing or not expressing an siRNA-resistant form of CALM wild type (wt) or CALM 219 mutant, as indicated. The cells were lysed and subjected to western blotting. The knockdown efficiency, LC3-II levels and the level of the siRNA-resistant form of CALM are shown on the western blotting.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(b) LC3 dots counting in CALM knockdown cells. CALM was knocked down in cells expressing GFP-LC3 with or without an siRNA-resistant form of CALM wild type (wt) or CALM mutant (219 mutant) as indicated. The cells were kept in full medium or starved in Hanks balanced salt solution (HBSS) for 4 h, fixed and subjected to microscopy to score the number of LC3 dots per cell. The ratio of the number of LC3 dots per cell (shown as mean ±s.d.) between starvation and basal conditions is shown on the graph (*P0.01; NS, not significant, two-tailed t-test; n≥300 cells per condition; BC, basal conditions).",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(c) Co-localization between ATG9A and VAMP3-HA or GFP-LC3 and VAMP8-HA in control and CALM knockdown HeLa cells stably expressing VAMP3-HA or VAMP8-HA. Confocal pictures are shown with magnified areas showing co-localization between ATG9A and VAMP3 or GFP-LC3 and VAMP8 in control cells and no co-localization in CALM knockdown cells. Quantification of ATG9A-VAMP3 or GFP-LC3-VAMP8 co-localization is shown on the graph as a Pearson's coefficient (data are mean ±s.d.; *P0.05; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "LC3: 440738///81631///84557
CALM: 8301
VAMP3: 9341
VAMP8: 8673"
  },
  {
    "caption": "(a) Co-localization between ATG12 and VAMP2-HA in control and CALM knockdown HeLa cells stably expressing VAMP2-HA. Confocal pictures are shown with magnified areas on the right showing co-localization between ATG12 and VAMP2 in control cells and no co-localization in CALM knockdown cells. Quantification of ATG12-VAMP2 co-localization is shown on the graph as the Pearson's coefficient (data are mean ±s.d.;*P0.05; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "CALM: 8301"
  },
  {
    "caption": "(b) Western blot analysis of VAMP2, actin and LC3-II in HeLa cells where VAMP2 was knocked down, as indicated. The cells were starved in Hanks balanced salt solution (HBSS) and treated with Baf A1 as indicated. (SE, short exposure; LE, longer exposure.) Quantification of LC3-II/actin ratio is shown. Data are representative of three independent experiments and shown as mean ±s.d. (*P0.05; NS, not significant, two-tailed t-test).",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(c) LC3 dot counting in CALM and VAMP2 knockdown cells. CALM or VAMP2 were knocked down in cells expressing GFP-LC3. The cells were kept in full medium or starved in HBSS for 4 h, fixed and subjected to automated fluorescence microscopy to score the number of LC3 dots per cell. The number of LC3 dots per cell (shown as mean ±s.d.) is shown on the graph for each condition (n≥300 cells per condition; BC, basal conditions). (*P0.01; NS, not significant, two-tailed t-test).",
    "ncbi_link": "LC3: 440738///81631///84557
CALM: 8301
VAMP2: 6844"
  },
  {
    "caption": "(d) Number of p62 dots per cell in VAMP2 knockdown. HeLa cells where VAMP2 was knocked down were fixed and subjected to microscopy after labelling endogenous p62 using specific antibody. The data represent the number of p62 dots per cell shown as mean ±s.d. (*P0.05; two-tailed t-test; n≥300 cells per condition).",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(e) Percentage of huntingtinQ74-expressing cells with aggregates in VAMP2 knockdown HeLa cells. Data are from one representative experiments performed in triplicate, out of three independent experiments and shown as mean ±s.d. (*P0.05; two-tailed t-test).",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(f) Western blot analysis of VAMP2, actin and LC3-II in HeLa cells stably expressing VAMP2-HA wild type or VAMP2-HA mutated in the CALM-binding site at different levels (wild-type clone 6, wt Cl6: low level; wild-type clone 11, wt Cl11: high level; mutant clone 11, AA Cl11: low level; mutant clone 12, AA Cl12: high level). The cells were treated with Baf A1 as indicated. (SE, short exposure; LE, longer exposure). Quantification of LC3-II/actin ratio is shown. Data are representative of three independent experiments and shown as mean ±s.d. (*P0.05; two-tailed t-test).",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(a) Size of endogenous ATG12 vesicles in HeLa cells stably expressing either wild-type or mutant VAMP2. Confocal pictures are presented with magnified areas showing ATG12 vesicles. Data are representative of three independent experiments and shown as mean ±s.d. (n≥100 vesicles; *P0.05; two tail t-test). Scale bars, 5 μm.",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(b) Co-localization between ATG12 and LC3 in HeLa cells stably expressing either wild-type clone 11 or mutant clone 12 VAMP2. Confocal pictures are presented with magnified areas showing ATG12-LC3 co-localization. The Pearson's coefficient between ATG12 and LC3 is shown. Data are representative of three independent experiments and shown as mean ±s.d. (n≥100 vesicles; *P0.05; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(c) Size and number of endogenous ATG12 vesicles in VAMP2-knockdown HeLa cells in starvation condition. Confocal pictures are shown with arrows indicating ATG12 vesicles. Data are representative of three independent experiments and shown as mean ±s.d. for the size of ATG12 vesicle. (n≥100 vesicles; *P0.05; based two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(d) Live-cell imaging of ATG16L1-GFP in VAMP2-knockdown HeLa cells. Confocal pictures from various time points of a 5-min movie are shown in inverted greyscale. Arrows indicate ATG16L1null. The number of fusion events per vesicles is shown. Data are representative of five movies and shown as mean ±s.d. (*P0.05; two-tailed t-test). Scale bars, 5 μm.",
    "ncbi_link": "VAMP2: 6844"
  },
  {
    "caption": "(e) In vitro fusion assay of post-nuclear supernatants from control and VAMP2 knockdown HeLa cells expressing either GFP-ATG16L1 or mStrawberry-ATG16L1. Confocal pictures are shown where ATG16L1-mStrawberry signal is shown in purple to enable better visualization. Fused vesicles appear in white. The ATP-negative condition, which prevents SNARE-dependent fusion, is also shown as a control of reaction. Magnified areas are shown to allow visualization of the vesicles. The percentage of fused vesicles (white) is represented. Data are representative of two independent experiments and shown as mean ±s.d. (n≥100 vesicles). Scale bars, 5 μm. (*P0.05; two-tailed t-test). n=numbers of vesicles scored per field.",
    "ncbi_link": "ATG16L1: 55054
VAMP2: 6844"
  },
  {
    "caption": "(a) Western blotting showing downregulation of lap (i) or increase in Atg8a-II (ii) expression level in adult fly heads on lap downregulation using the UAS-RNAi lines lapGD12732 or lapKK105767, or the heterozygous allele lap1. Quantification of lap/actin and Atg8a-II/actin is shown. Genotypes: Control w; elav-GAL4/+; for the RNAi lines: w; elav-GAL4/ lapKK105767 and w; elav-GAL4/+; lapGD12732/+; for the lap1 allele: w; elav-GAL4/+; lap1/+.",
    "ncbi_link": "lap: 36670"
  },
  {
    "caption": "(b) Western blotting showing the accumulation of tau in Drosophila adult flyheads on lap downregulation using the UAS-RNAi lines lapGD12732 or lapKK105767, or the heterozygous allele lap1. Quantification of tau/lapGD12732 is shown. Genotypes: Control w; elav-GAL4/+; for tau-WT: w; elav-GAL4/+; UAS-tau-WT/+; for RNAi lines: w; elav-GAL4/ lapKK105767; UAS-tau-WT/+ and w; elav-GAL4/+; lapGD12732/tau-WT; for the lap1 allele: w; elav-GAL4/+; lap1/+ or w; elav-GAL4/+; lap1/UAS-tau-WT.",
    "ncbi_link": "lap: 36670"
  },
  {
    "caption": "(ai) Western blot analysis of tubulin, LC3-I and LC3-II in zebrafish larvae where ATG7 was downregulated, as indicated. (ii) Western blot analysis of CALM-HA, actin and LC3-II in zebrafishlarvae where CALM-HA was expressed, as indicated. The larvae were treated with ammonium chloride (NH4Cl), as indicated. (SE, short exposure; LE, longer exposure). Quantification of LC3-II/actin ratio is shown. Data are representative of three independent experiments and shown as mean ±s.d. (*P0.05; two-tailed t-test).",
    "ncbi_link": "ATG7: 100333016
CALM: 334855"
  },
  {
    "caption": "(c) Dendra-tau clearance in the presence of CALM: representative images of CALM with mosaic expression of Dendra-tau and full-length Dendra-tau taken immediately after photoconversion and at 6, 24, 30, 48 and 54 h after conversion. The fluorescence intensity of individual cells was quantified and mean fluorescent intensity of cells co-expressing Dendra-tau and either full-length CALM or Δ-ANTH CALM (larvae-ANTH-HA) constructs (n≥ 100 cells, ≥9 larvae per treatment group) at each time point was calculated. (i) Expression of full-length HA significantly delayed the clearance of CALM at all time points compared with Δ-ANTH CALM (***P0.001, one-way ANOVA). One graph, representative of three independent experiments, is presented. (CALM-ANTH-HA: 132 cells, 20 fishes; CALM-CALM: 18 cells, 8 fishes). Another two experiments are shown in Supplementary Fig. S5C. Error bars are mean ±s.d. (ii) Treatment with CALM alters the dynamics of CALM clearance. Expression of full-length CALM significantly delayed the clearance of CALM at all time points compared with Δ-ANTH CALM, as observed in i (P0.001, one-way ANOVA). However, treatment of Δ-ANTH CALM injected CALM with CALM slows the CALM clearance by 70% to a level comparable to that observed in larvae injected with full-length Dendra-tau. Ammonium chloride treatment of Dendra-tau injected with full-length null results in a modest (22%) decrease in Dendra-tau clearance, suggesting that CALM overexpression and ammonium chloride treatment have a cumulative effect (n≥25 cells, n≥9 Dendra-tau per treatment group). Error bars are mean ±s.d. Note that i and ii are distinct experiments.",
    "ncbi_link": "CALM: 334855"
  },
  {
    "caption": "(a) rho::GFP-tau fishes were incubated from 3 to 9 d.p.f. in either dimethyl sulphoxide (DMSO) or rapamycin (i) or from 3 to 7 d.p.f in EM alone or 10 mM ammonium chloride or 100 nM Wortmannin (ii). Images through the central retina at 9 d.p.f. (top panel; (i)) reveal rod degeneration (arrow) throughout the retina in control (DMSO-treated) larvae, whereas rod photoreceptors are present throughout the retina, particularly in the central region following treatment with rapamycin (arrow). Images taken through the central retina at 7 d.p.f. (bottom panel; (ii)) show normal photoreceptors in the marginal zones (arrows) and only limited numbers in the central region. NH4Cl exacerbates degeneration-photoreceptors are absent from the central retina and reduced/absent from marginal zones (arrows). Sections were stained with anti-rhodopsin (1D1) antibody. GFP labels whole rod photoreceptors, whereas rhodopsin is present in the rod outer segment. GFP co-localizes with the red rhodopsin label in all experimental conditions. Scale bars, 50 μm. Quantification of rodphotoreceptor degeneration (n=10 larvae per group; ***P0.001; ###P0.001, two-tailed unpaired t-test). Error bars are mean ±s.d.",
    "ncbi_link": "rho: 30295
tau: 569098"
  },
  {
    "caption": "(b) Full-length CALM electroporation into rho::GFP larvae did not cause degeneration., while full-length CALM electroporation into rho::GFP-tau larvae exacerbated photoreceptor degeneration. Central retina sections in the region of the optic nerve head are presented. Scale bars, 50 μm. Data represent the ratio (in %) of the intensity of the GFP signal between CALM-HA electroporated eye versus control eye for five individuals per transgenic line. ***P0.05; two-tailed t-test. Error bars are mean ±s.d.",
    "ncbi_link": "CALM: 334855
rho: 30295"
  },
  {
    "caption": "(c) NH4Cl treatment of rho::GFP-tau immediately after unilateral CALM electroporation caused photoreceptor degenerationon the control (non-electroporated) side but did not alter the degeneration caused by CALM electroporation. Rapamycin treatment of Rapamycin::GFP-tau immediately after unilateral CALM electroporation rescued photoreceptors on the control (non-electroporated) side but not on the CALM-electroporated side. To demonstrate that loss of GFP corresponds to loss of photoreceptors, sections were stained with anti-rhodopsin (1D1) antibody. Wilcoxon signed rank test was used to compare the left eye versus the right eye of the same fish; Mann-Whitney test was used to compare drug treatment in the right eye of different fishes. *P0.05. Scale bars, 50 μm. Error bars are mean ±s.e.m.",
    "ncbi_link": "CALM: 334855
rho: 30295
tau: 569098"
  },
  {
    "caption": "(a) Histological section to demonstrate the individual cell layers of the zebrafish retina. The photoreceptor layer (PR, comprising rod and cone photoreceptors) lies immediately adjacent to the retinal pigment epithelium (RPE) at the outermost surface of the eye. Thioflavin-S labelling of retinal sections was used to identify neurofibrillary tangles in the photoreceptor layer (marked with yellow dotted lines). No labelling was observed in the retina of rho::GFP at 8 d.p.f., whereas distinct thioflavin-S-positive tangles (arrows) were observed in the photoreceptor layer of rho::GFP-tau fish. Note, the RPE is highly autofluorescent due to the presence of silver pigment. High power regions are shown in the top right of each panel.",
    "ncbi_link": "rho: 30295
tau: 569098"
  },
  {
    "caption": "(b) Unilateral electroporation of CALM into the retina of rho::GFP-tau zebrafish resulted in a marked increase in thioflavin-S positive tangles in the electroporated retina in the photoreceptor layer (PR) compared with the control side. Top panel are lower magnification images to show the retinal cell layers. Thioflavin-S labelling is restricted to the PR layer. Note the RPE is highly autofluorescent due to the presence of silver pigment. Bottom panel are higher magnification images to show individual thioflavin-S tangles the largest of which are indicated by arrows.",
    "ncbi_link": "CALM: 334855
rho: 30295
tau: 569098"
  },
  {
    "caption": "C. Response of  HyPer7 probes targeted to indicated compartments to treatment of mtDAO-expressing HEK293  cells with 2 mM  D-Ala (cells generated with the Flp-In T-REX-system). HEK293  cells were grown either with  glucose (black curve and data points) or galactose  (red curve and data points) as carbon  source. Solid line represents average, points colored in the lighter version of the respective color are the corresponding ratios measured in individual cells. Data information: As most of the data were not normal distributed, instead of a t-test, a Wilcoxon/Mann-Whitney-U-test was performed and samples were compared in pairs. ***, p ≤ 0.001",
    "ncbi_link": "DAO: "
  },
  {
    "caption": "B.  Peroxiredoxin levels in peroxiredoxin 1  (PRDX1 KO) and peroxiredoxin 2 (PRDX2  KO) knockout cells. quantitative  proteomics  (n = 4, technical replicates) The right subpanel of B lists the identified proteins belonging to cellular antioxidative systems which are not altered for PRDX1 KO or PRDX2  KO, respectively. In both quantitative  proteomics  experiments 4403 proteins were detected in total.",
    "ncbi_link": "peroxiredoxin 1: 5052
PRDX1: 5052
peroxiredoxin 2: 7001
PRDX2: 7001"
  },
  {
    "caption": "D. Response of HyPer7 probes targeted to indicated compartments to treatment of mtDAO-expressing cell lines with 4 mM D-Ala (black, wild type; red, PRDX1  KO; blue, PRDX2  KO; cell generated with the piggyBAC system). Cells were grown in glucose-containing medium. Solid line represents average, points colored in the lighter version of the respective color are the corresponding ratios measured in individual cells. Data information As most of the data were not normal distributed, instead of a t-test, a Wilcoxon/Mann-Whitney-U-test was performed and samples were compared in pairs. *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001",
    "ncbi_link": "DAO: 
PRDX1: 5052
PRDX2: 7001"
  },
  {
    "caption": "B. Peroxiredoxin levels in peroxiredoxin 1 and 2 double knockout cells (PRDX1/2 DKO). quantitative proteomics (B).The right subpanel in (B) lists all detected but not altered proteins belonging to cellular antioxidative systems.",
    "ncbi_link": "peroxiredoxin 1: 5052
PRDX1: 5052"
  },
  {
    "caption": "E. Response of HyPer7 probes targeted to indicated compartments to treatment of mtDAO-expressing cell lines with 4 mM D-Ala  (black, wild type; red, PRDX1/2 DKO; cell generated with the piggyBAC system). Cells were grown in glucose-containing medium. Solid line represents average, points colored in the lighter version of the respective color are the corresponding ratios measured in individual cells. Data information: Statistical analysis was only performed to compare the PRDX1/2 DKO with the wildtype. As most of the data were not normal distributed, instead of a t-test, a Wilcoxon/Mann-Whitney-U-test was performed and samples were compared in pairs. *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001",
    "ncbi_link": "DAO: 
PRDX1: 5052"
  },
  {
    "caption": "(B) Growth inhibition upon overexpression of HOS3-NLS driven by the GAL1 promoter is suppressed by overexpression of the KAT Esa1. 10-fold serial dilutions of the indicated strains transformed with an empty vector or with the indicated plasmids, were spotted onto SC-Glu and SC-Gal medium (to activate the GAL1 promoter) and incubated at 25 °C for 3 days. Note that HOS3-NLS (under the control of the native HOS3 promoter) does not affect cell growth.",
    "ncbi_link": "Esa1: 854418
GAL1: 852308
HOS3: 855987"
  },
  {
    "caption": "(C) esa1-ts and gcn5Δ esa1-ts mutants have bud emergence defects. (Top) Cells of the indicated strains were arrested in G1 by treatment with ɑ-factor for 2.5 h at 25 ºC, shifted to 37 ºC for 1 h and released from the G1 arrest at 37 ºC. Cells were fixed at the indicated times and the presence of buds was assessed by microscopy. Mean and SEM are derived from n = number of independent experiments. At least 200 cells were scored for each strain and time point. (Bottom) Bright field images of the indicated strains 60 min after the ɑ-factor washout. Arrowheads point to cell buds. Scale bar, 4 µm.",
    "ncbi_link": "esa1: 854418
gcn5: 853167"
  },
  {
    "caption": "(D) Inactivation of ESA1 and GCN5 delays DNA replication. Cells of the indicated genotypes were synchronised as in panel C, and DNA content was evaluated by flow cytometry. Numbers indicate time in minutes after the release. This experiment was repeated three times with similar results; one experiment is shown.",
    "ncbi_link": "ESA1: 854418
GCN5: 853167"
  },
  {
    "caption": "(A) Overexpression of Esa1 and Gcn5 KATs leads to increased acetylation levels of the nuclear basket nucleoporin Nup60. (Top) Nup60-GFP was immunoprecipitated from extracts of the indicated strains, and its acetylation state probed with anti-AcLys antibodies. (Bottom) Total extracts probed with anti-HA antibodies to verify KAT overexpression.",
    "ncbi_link": "Esa1: 854418
Gcn5: 853167"
  },
  {
    "caption": "(B) nup60-KN partially rescues the budding defect of esa1-ts cells. (Left) Budding of cells of the indicated strains were determined as in Figure 1C. At least 200 cells were scored for each strain and time point. Data from 3 independent experiments is represented as mean and SEM (esa1-ts, esa1-ts nup60-KN). (Right) Bright field images of the indicated strains 40 min after the ɑ-factor washout. Arrowheads point to cell buds. Scale bar, 4 µm.",
    "ncbi_link": "esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(C) mRNA levels of CLN2, CDC21, SVS1, and RNR1 were determined for cells of the indicated strains after G1 arrest and release at restrictive temperature, with samples collected at indicated times. Data from 3 independent experiments is represented as mean and SEM.",
    "ncbi_link": "CDC21: 854241
CLN2: 855819
RNR1: 856801
SVS1: 855940"
  },
  {
    "caption": "(D) nup60-KN mutation partially rescues the delay in synthesis of the G1/S cyclin Cln2 in esa1-ts cells. Cells of the indicated strains were processed as in (B) and the amount of Cln2-HA protein at the indicated times was assessed by western blot. % of budded cells is indicated below for each corresponding strain and time point. Note the slow, inefficient budding in esa1-ts mutants. In WT, the reduction of Cln2 at 60 min and its increase at 90 min reflects the start of a second cycle, which is absent in esa1-ts cells.",
    "ncbi_link": "esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(E) nup60-KN partially rescues the Whi5 export defect of esa1-ts daughter cells. Composite of bright field and Whi5-mCherry (left) and quantification of Whi5 nuclear export (right) in mother (M) and daughter (D) cells of the indicated strains. Whi5 export (arrows) is delayed in esa1-ts mothers and daughters compared to WT (p < 000.1, Log-rank Mantel-Cox test); esa1-ts nup60-KN advances Whi5 export relative to esa1-ts in daughters (p=0.0105), but not in mothers (p > 0.05). 3 z-confocal slices spaced 0.5 µm were acquired every 3 min; maximum projections of selected timepoints are shown. Time is indicated in minutes; t=0 marks Whi5 nuclear import. Scale bar, 5 µm. n = number of cells, pooled from two independent experiments with similar results.",
    "ncbi_link": "esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(A) Composite of bright field and Whi5-tdTomato (BF/Whi5) and CLN2-PP7 mRNA labelled with PCP-NLS-GFP (CLN2 mRNA) in mother (M) and daughter (D) cells of the indicated strains. Arrows indicate nuclear foci. Brighter GFP nucleoplasmic areas may correspond to the nucleolus. Insets show enhanced-contrast images to visualise cytoplasmic mRNA particles (arrowheads). Numbers indicate minutes relative to Whi5 nuclear import. Maximum projections of whole-cell Z-stacks are shown for Whi5 and CLN2 mRNA except in the inset and in selected esa1-ts images, where single Z-slices are shown for clarity. Scale bar: 4 µm (inset: 1 µm).",
    "ncbi_link": "GFP: 
CLN2: 855819
PCP: 1261104
esa1: 854418"
  },
  {
    "caption": "(B) Fraction of cells of the indicated strains with nuclear CLN2-PP7 mRNA foci, aligned relative to Whi5 import. Symbols represent individual values; lines were generated by smoothing of the nearest 3 neighbouring values (0th order polynomial). (C) Fraction of cells of the indicated strains with nuclear CLN2-PP7 mRNA foci, aligned relative to Whi5 export.",
    "ncbi_link": "CLN2: 855819"
  },
  {
    "caption": "(D) Mean fluorescence intensity of nuclear CLN2 mRNA foci at the time of Whi5 export, normalised relative to the nuclear background. Data information boxes include 50% of data points, lines represent the median and whiskers extend to maximum and minimum values. ****, p ≤ 0.0001; **, p ≤ 0.01; n.s., p > 0.05, ordinary one-way ANOVA with Tukey multiple comparisons test. Adjusted p-values in (D): WT vs. esa1-ts p < 0.0001, WT vs. esa1-ts nup60-KN p < 0.0001, esa1-ts vs. esa1-ts nup60-KN p = 0.9845 Foci were scored in individual Z-slices spanning the entire cell volume. n = number of cells, pooled from two independent experiments with similar results.",
    "ncbi_link": "CLN2: 855819
esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(E) Number of cytoplasmic CLN2-PP7 mRNA foci in early G1 (5 minutes after Whi5 import) and at the G1/S transition (5 min after Whi5 export). Data information: boxes include 50% of data points, lines represent the median and whiskers extend to maximum and minimum values. ****, p ≤ 0.0001; **, p ≤ 0.01; n.s., p > 0.05, ordinary one-way ANOVA with Tukey multiple comparisons test. Adjusted p-values in (E): WT vs. esa1-ts p < 0.0001, esa1-ts vs. esa1-ts nup60-KN p = 0.002. Foci were scored in individual Z-slices spanning the entire cell volume. n = number of cells, pooled from two independent experiments with similar results.",
    "ncbi_link": "CLN2: 855819
esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(F) The position of nuclear CLN2-PP7 foci (marked with arrowheads in the examples) was scored relatively to the nuclear periphery (visualised with PCP-NLS-GFP) in the indicated strains. The fraction of non-perinuclear CLN2-PP7 foci is significantly increased in esa1-ts cells compared to the WT and rescued by nup60-KN mutation (two-sided Fisher's exact test p = 0.0209 and p = 0.0227). Scale bar, 1 µm.",
    "ncbi_link": "GFP: 
CLN2: 855819
PCP: 1261104
esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(B) Overexpression of MEX67 and MTR2 rescues the lethality of Hos3-NLS overexpression. 10-fold serial dilutions of the indicated strains transformed with the indicated plasmids spotted onto SC-Glu and SC-Gal medium and incubated at 25 °C for 3 days.",
    "ncbi_link": "Hos3: 855987
MEX67: 855934
MTR2: 853649"
  },
  {
    "caption": "(C) A high-copy plasmid containing SAC3 rescues the lethality of Hos3-NLS overexpression. Strains carrying a high copy plasmid containing the SAC3 ORF (nucleotides 467-3905), or the empty vector, were grown",
    "ncbi_link": "Hos3: 855987
SAC3: 851737"
  },
  {
    "caption": "(D) Overexpression of Hos3-NLS promotes nuclear accumulation of mRNA. (Left) Cultures of the indicated strains were treated with galactose overnight to induce HOS3-NLS expression, cells were fixed, and FISH was performed using Cy3-Oligo(dT). (Right) The fraction of cells with nuclear mRNA accumulation was determined for the indicated strains and conditions. Data information: , arrows point to polyadenylated RNA in the nucleus, which was visualised by DAPI staining. Data from 3 independent biological replicates (7h30) is represented as mean and s.d., and data from 2 independent biological replicates (0 and 3h30) as mean and range. *, p ≤ 0.05; ***, p ≤ 0.001; ns, p > 0.05, two-tailed unpaired t-test. At least 200 cells were scored for each time-point and condition. Scale bar, 4 µm.",
    "ncbi_link": "Hos3: 855987
HOS3: 855987"
  },
  {
    "caption": "(E) Inactivation of Esa1 impairs export of poly(A) RNA. (Left) Cultures of the indicated strains were incubated at 37 ºC. (Right) The fraction of cells with nuclear mRNA accumulation was determined for the indicated strains and conditions Data information: , arrows point to polyadenylated RNA in the nucleus, which was visualised by DAPI staining. Data from 3 independent biological replicates (7h30) is represented as mean and s.d., and data from 2 independent biological replicates (0 and 3h30) as mean and range. *, p ≤ 0.05; ***, p ≤ 0.001; ns, p > 0.05, two-tailed unpaired t-test. At least 200 cells were scored for each time-point and condition. Scale bar, 4 µm.",
    "ncbi_link": "Esa1: 854418"
  },
  {
    "caption": "(F) nup60-KN mutation partially rescues the mRNA export defects of esa1-ts. Cells of the indicated strains were processed Data information: arrows point to polyadenylated RNA in the nucleus, which was visualised by DAPI staining. Data from 3 independent biological replicates (7h30) is represented as mean and s.d., and data from 2 independent biological replicates (0 and 3h30) as mean and range. *, p ≤ 0.05; ***, p ≤ 0.001; ns, p > 0.05, two-tailed unpaired t-test. At least 200 cells were scored for each time-point and condition. Scale bar, 4 µm.",
    "ncbi_link": "esa1: 854418
nup60: 851263"
  },
  {
    "caption": "(A) Depletion of Hos3 or expression of acetyl-mimic Nup60 (nup60-KN) increases the nuclear localisation of Sac3 in G1. Cells of the indicated strains were imaged by time-lapse microscopy and the fluorescence levels of the indicated proteins were determined in G1 (after cytokinesis). The NPC component Nup49 was used as a control for Nuclear Pore Complex protein levels. Fluorescence intensity was measured in sum projections of whole-cell Z-stacks, by segmentation of either the nuclear area in the mCherry channel, or of the whole cell in the brightfield channel. The ratio of Sac3/Nup49 intensities was then normalised relative to the mean intensity of wild-type mothers. Data information arrowheads point to daughter cells boxes include 50% of data points, the line represents the median and whiskers extend to maximum and minimum values. ****, p ≤ 0.0001; ns, p > 0.05, two-tailed unpaired t-test. Scale bar, 2 µm. n = number of cells, pooled from three independent experiments with similar results.",
    "ncbi_link": "Hos3: 855987
Nup60: 851263
nup60: 851263"
  },
  {
    "caption": "(B) Inactivation of Esa1 decreases Sac3 nuclear levels. Wild-type (WT) and esa1-ts cells were arrested in mitosis by treatment with nocodazole at 25 ºC, shifted to 37 ºC, released from the mitosis block in fresh medium at 37 ºC, and imaged by time-lapse microscopy. Fluorescence levels were quantified in G1 Data information: arrowheads point to daughter cells boxes include 50% of data points, the line represents the median and whiskers extend to maximum and minimum values. ****, p ≤ 0.0001; ns, p > 0.05, two-tailed unpaired t-test. Scale bar, 2 µm. n = number of cells, pooled from three independent experiments with similar results.",
    "ncbi_link": "Esa1: 854418
esa1: 854418"
  },
  {
    "caption": "(C) Rapamycin-dependent dimerisation abolishes Sac3 mother/daughter asymmetries. NUP60-mCherry-FKBP SAC3-GFP-FRB cells were incubated with rapamycin (RAPA) to trigger FRB-FKBP heterodimerization, or with DMSO as control. Fluorescence levels were quantified in G1 cells 15 to 30 minutes after addition of the drug. Data information arrowheads point to daughter cells, boxes include 50% of data points, the line represents the median and whiskers extend to maximum and minimum values. ****, p ≤ 0.0001; ns, p > 0.05, two-tailed unpaired t-test. Scale bar, 2 µm. n = number of cells, pooled from three independent experiments with similar results.",
    "ncbi_link": "GFP: 
mCherry: 
FKBP: 2280
FRB: 2475
NUP60: 851263
SAC3: 851737"
  },
  {
    "caption": "(D) Sac3 anchoring to the nuclear basket advances Start in esa1-ts daughter cells. Composite of bright field and Whi5-mGFP (top) and quantification of Whi5 nuclear export timing (bottom) in wild-type (WT) and esa1-ts mother (M) and daughter (D) cells treated with either rapamycin (RAPA) or DMSO and expressing Nup60-FRB and Sac3-mCherry-FKBP. Sac3 anchoring to Nup60 does not alter Whi5 export timing in WT mother or daughter cells (DMSO vs RAPA, p > 0.05, Log-rank Mantel-Cox test), but it advances Whi5 export in esa1-ts daughters (p = 0.0001). Whi5 export efficiency was slightly improved also in mother cells (p = 0.0374). 8 z-confocal slices spaced 0.4 µm were acquired every 3 min; maximum projections are shown. Time is indicated in minutes; t=0 marks Whi5 nuclear import. Scale bar, 5 µm. Data information: arrowheads point to Whi5 export.",
    "ncbi_link": "esa1: 854418"
  },
  {
    "caption": "(A) Time Lapse microscopy of WT and nup60-KN cells expressing GAL1pr:sfGFP and Nup60-mCherry at the indicated times of galactose induction. Scale bar, 4 µm.",
    "ncbi_link": "nup60: 851263"
  },
  {
    "caption": "(B) Depletion of Hos3, and expression of acetyl-mimic Nup60 (nup60-KN) enhances GAL1 expression. WT, hos3Δ, nup60-KN and nup60-KN hos3Δ cells were shifted to galactose and imaged by time-lapse microscopy to monitor GAL1pr:sfGFP expression during 7 hours. Nuclear fluorescence was scored by segmentation of the nuclear area in the mCherry channel and mean fluorescence of nuclear GFP and Nup60-mCherry was quantified from sum projections of whole-cell Z-stacks at the indicated times. At least 200 cells were scored for each strain and time point. Shaded areas indicate the SEM.",
    "ncbi_link": "Hos3: 855987
hos3: 855987
Nup60: 851263
nup60: 851263"
  },
  {
    "caption": "(C) mRNA levels of GAL1 were determined for wild type (WT) and nup60-KN cells at the indicated times after galactose addition. One of two independent experiments with similar results is shown (mean and SEM from 3 technical replicates).",
    "ncbi_link": "GAL1: 852308
nup60: 851263"
  },
  {
    "caption": "(E) Expression of GAL1pr:sfGFP induced with galactose (left) or ß-estradiol (right), in the presence of the ß-estradiol-dependent transactivator Gal4-ER-VP16. Smooth lines show GFP fluorescence intensity (left x axis); lines with circles show the difference in GFP intensity between the indicated strains (right x axis). The difference between wild type and hos3∆, and between wild type and nup60-KN, increases continuously over time in response to galactose, but not to ß-estradiol.",
    "ncbi_link": "ER: 2099
Gal4: 855828
hos3: 855987
nup60: 851263
VP16: 24271473"
  },
  {
    "caption": "(A) Cells of the indicated strains were incubated with galactose in the presence of either rapamycin (RAPA) to induce FRB-FKBP heterodimerization, or DMSO as control. GAL1pr:sfGFP expression was monitored over time",
    "ncbi_link": "FKBP: 2280
FRB: 2475"
  },
  {
    "caption": "(B) Representative IF images in CHME3 stably expressing Flag alone control or the Flag-tagged EB1 constructs depicted in A co-stained for Tyrosinated-MTs (Tyr-MTs), and the nucleus (Hoechst). Scale bar, 10 μm.",
    "ncbi_link": "Flag: 
EB1: 22919"
  },
  {
    "caption": "(C) HIV-1-VSV-luc infection is enhanced in CHME3 depleted of endogenous EB1 and stably expressing full-length (FL) EB1, but not in control Flag or any of the other EB1 constructs depicted in A.",
    "ncbi_link": "Flag: 
EB1: 22919"
  },
  {
    "caption": "(D) Increasing amount of FL-EB1, but not ∆EEY results in a dose-dependent enhancement of HIV-1-VSV-luc infection in transiently transfected CHME3 cells.",
    "ncbi_link": "EB1: 22919"
  },
  {
    "caption": "HIV-1-VSV-luc (E) infection is reduced in differentiated THP-1 depleted of CLIP170 determined by luciferase assays or FACS analysis, respectively.",
    "ncbi_link": "CLIP170: 6249"
  },
  {
    "caption": "HIV-1-VSV-ZsGreen at various dilutions (corresponding to multiplicities of infection (m.o.i) 0.06, 0.03 and 0.02) (F) infection is reduced in differentiated THP-1 depleted of CLIP170 determined by luciferase assays or FACS analysis, respectively.",
    "ncbi_link": "CLIP170: 6249"
  },
  {
    "caption": "(G) HIV-1-WT-luc infection is decreased in CLIP170 depleted CHME3 cells.",
    "ncbi_link": "CLIP170: 6249"
  },
  {
    "caption": "Effects of CLIP170 on fusion of viral particles by endocytosis. CHME3 cells either treated with control or CLIP170 siRNAs (A) were infected with Mock or HIV-1-VSV-BlaM-Vpr. Representative FACS analysis of cells (n = 3) showing ∼ 9% (Control siRNA) and 3% (CLIP170 siRNA) shift (A) from green (uncleaved CCF2) to blue (cleaved CCF2). % infected cells is indicated at the top left corner of each plot and quantification from independent repeats is presented as bar graphs at the right side of each FACS plot.",
    "ncbi_link": "CLIP170: 6249"
  },
  {
    "caption": "HIV-1-VSV-luc infection is enhanced in Flag-CLIP170, but not in Flag control, expressing CHME3 cells.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "Effects of CLIP170 on fusion of viral particles by endocytosis. CHME3 cells expressing Flag control or Flag-CLIP170 (D) were infected with Mock or HIV-1-VSV-BlaM-Vpr. Representative FACS analysis of cells (n = 3) showing no difference (D) from green (uncleaved CCF2) to blue (cleaved CCF2). % infected cells is indicated at the top left corner of each plot and quantification from independent repeats is presented as bar graphs at the right side of each FACS plot.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "(E) The percentage fused double-labelled (GFP-Vpr+/S15-tomato-) HIV-1-DL-WT are not affected in CHME3 cells depleted of CLIP170. Data represent mean of ≥895 virus particles analyzed in ≥11 fields of view (≥17 cells) for each condition. One-way ANOVA was used to calculate statistical significance (mean ±SEM).",
    "ncbi_link": "GFP: 
tomato: 
CLIP170: 6249
S15: 6209
Vpr: 155807"
  },
  {
    "caption": "(F) Percentage HIV-1-WT-GFP-Vpr particles within 2 μm of the nucleus is reduced in CHME3 depleted of CLIP170 at 2 and 4 h.p.i, scatterplot with mean of ≥354 virus particles quantified in ≥13 cells per sample. Statistical significance was determined by one-way ANOVA * = p<0.05, *** = p<0.001.",
    "ncbi_link": "CLIP170: 6249"
  },
  {
    "caption": "(I) The induction of Ac-MTs is blocked in HIV-1-VSV-luc (Virus) infected, but not in uninfected (NI) or Mock infected CHME3 depleted of EB1, but not CLIP170 at 6 h.p.i. Tyrosinated MTs (Tyr-MTs) are not affected. Representative fields are shown. Similar results were obtained in three independent experiments. Scale bar, 50 μm.",
    "ncbi_link": "CLIP170: 6249
EB1: 22919"
  },
  {
    "caption": "CHME3 treated with negative control, EB1 or CLIP170 siRNAs were either lysed and analyzed by WB Molecular weight markers (in kDa) are shown to the right of WBs in A.",
    "ncbi_link": "CLIP170: 6249
EB1: 22919"
  },
  {
    "caption": "CHME3 treated with negative control, EB1 or CLIP170 siRNAs were infected with GFP-Vpr/S15-tomato-labeled VSV-G pseudotyped HIV-1 (B). Scatterplot of maximum p24 intensity of fused viral particles normalized to the control mean.",
    "ncbi_link": "CLIP170: 6249
EB1: 22919"
  },
  {
    "caption": "(C-D) Amounts of pelleted p24 CA normalized to the input CA at 3 h.p.i. with HIV-1-VSV-luc in 293A (C) or CHME3 (D) treated with control, EB1 or CLIP170 siRNAs. Mean +/- SEM from three independent experiments is shown. Statistical significance was determined by one-way ANOVA. Error bars = standard error of the mean (* = p-value ≤0.05, ** = p-value ≤0.01, *** = p-value ≤0.001).",
    "ncbi_link": "CLIP170: 6249
EB1: 22919"
  },
  {
    "caption": "Representative (n=3) WB analysis demonstrating that while GAPDH-HA control do not bind (A FEZ1-Flag control pelleted with in vitro assembled HIV-1 CA-NC complexes.",
    "ncbi_link": "FEZ1: 
Flag: 
GAPDH: 
HA: "
  },
  {
    "caption": "Representative (n=3) WB analysis demonstrating that while EB1-Flag do not bind pelleted with in vitro assembled HIV-1 CA-NC complexes.",
    "ncbi_link": "Flag: 
EB1: 22919"
  },
  {
    "caption": "Representative (n=3) WB analysis demonstrating that while Flag-CLIP170 pelleted with in vitro assembled HIV-1 CA-NC complexes.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "(F) Flag-CLIP170, but not Flag control, also binds to fractions containing intact HIV-1 cores (Virus #8 and #9) but not with Mock fractions.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "(G) HIV-1-WT-luc infection is increased in CHME3 cells stably expressing Flag-CLIP170, but not control Flag or Flag-CLIP170ΔCAPgly. Molecular weight markers (in kDa) are shown to the right of WBs.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "(H) Representative images (n=3) of CHME3 expressing Flag-CLIP170 or Flag-CLIP170ΔCAPgly stained for Flag and Tyr-MTs. Scale bar, 10 μm.",
    "ncbi_link": "Flag: 
CLIP170: 65201"
  },
  {
    "caption": "(C) Quantification (n=3) of the association of each protein with 97 to 137 CA-NC complexes, using untransfected lysates (Control) and EB1-Flag as controls for non-specific background staining.",
    "ncbi_link": "Flag: 
EB1: 22919"
  },
  {
    "caption": "(D) Lysates from untransfected, CypA-Flag- or Flag-CLIP170-transfected cells were subjected to CA-NC binding assays and WB analysis.",
    "ncbi_link": "Flag: 
CLIP170: 65201
CypA: 5478"
  },
  {
    "caption": "Anti-HA co-IP showing that GAPDH fused to the HIV-1 MHR (GAPDH-MHRhiv), but not HA-tagged GAPDH (GAPDH) binds to Flag-CLIP170 (C) in 293T cells. Results are representative of three experimental replicates.",
    "ncbi_link": "GAPDH: 
HA: "
  },
  {
    "caption": "Anti-HA co-IP showing that GAPDH fused to the HIV-1 MHR (GAPDH-MHRhiv) endogenous forms of various human SxIP-containing +TIPs, but not vimentin (D) in 293T cells. Results are representative of three experimental replicates.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Anti-HA co-IP showing that GAPDH fused to the HIV-1 MHR (GAPDH-MHRhiv) or to Flag-tagged SxIP fragment (Flag-Clasp2M) (E) in 293T cells. Results are representative of three experimental replicates.",
    "ncbi_link": "Flag: 
GAPDH: "
  },
  {
    "caption": "HIV-1-VSV-luc (Virus), but not uninfected (NI) or Mock, infection induces the formation of Ac-MTs in CHME3 expressing GAPDH-MHRhiv, but not GAPDH, as shown by WB analysis (F)",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "HIV-1-VSV-luc (Virus), but not uninfected (NI) or Mock, infection induces the formation of Ac-MTs in CHME3 expressing GAPDH-MHRhiv, but not GAPDH or imaging at 6 h.p.i (G). Scale bar, 15 μm. Representative fields are shown. Results are representative of three experimental replicates.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "(H) GAPDH-MHRhiv expression in CHME3 reduces infection with HIV-1-WT-luc. Statistical significance was determined by t test. * = p<0.05. Data are mean values from three independent experiments +/- SEM. Molecular weight markers (in kDa) are shown to the right of WBs.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "(C) Anti-HA co-IP in CHME3 expressing GAPDH-MHRhiv, GAPDH-MHRsiv or GAPDH-MHRmulv showing binding to endogenous CLIP170. Results are representative of three experimental replicates.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Anti-HA co-IP in Rhesus macaque FRhK4 (D) cells expressing GAPDH alongside GAPDH-MHRsiv",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Anti-HA co-IP in rat fibroblast Rat2 (E) cells expressing GAPDH alongside GAPDH-MHRmulv Anti-EB1 co-IP was included as positive control to demonstrate CLIP170 binding by EB1 in Rat2 cells. Results are representative of three experimental replicates.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Measurements of SIV-VSV-luc infectivity in FRhK4 (J) cells depleted of CLIP170. Statistical significance was determined by t test. *** = p<0.001. Data are mean values from two independent experiments +/- SEM.",
    "ncbi_link": "CLIP170: 702137"
  },
  {
    "caption": "Measurements of MuLV-VSV-luc infectivity in Rat2 (K) cells depleted of CLIP170.",
    "ncbi_link": "CLIP170: 65201"
  },
  {
    "caption": "(L) 293T transfected with GAPDH-MHRhiv or R162Q mutant (GAPDH-MHRhivQ) were subjected to anti-HA co-IP. Representative WB analysis is shown (n = 2). Molecular weight markers (in kDa) are shown to the right of WBs.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "D. Protein lysates from MM074, MM074BRAFi-R or MM074CDK7i-R were  immuno-blotted  for indicated proteins. Molecular sizes of the proteins are indicated (kDa). The numbers below the gel lanes represent relative protein level, which was determined from the band intensity using ImageJ software normalized to each relative  Vinculin  control.",
    "ncbi_link": "BRAF: 673
CDK7: 1022"
  },
  {
    "caption": "E-H. qRT-PCR analysis showing average TBP-normalized expression  of GATA6 (E), AMIGO2 (F), SERPINE1 (G) and ABCG2 (H) in the indicated cells treated with either siCTL or siGATA6 for 72h. Data information: data are presented as mean values + SD for six replicates (n=6). The p-value (Student's t-test) is indicated, **<0.01, ***<0.005 and ns=non-significant",
    "ncbi_link": "ABCG2: 9429
AMIGO2: 347902
GATA6: 2627
SERPINE1: 5054
TBP: 6908"
  },
  {
    "caption": "J. MM029 (left) and MM099 (right) were pre-treated with either siCTL or siGATA6 for 48h and treated with increasing concentrations of  THZ1 for 72h. Mean growth   is shown relative to vehicle (DMSO)-treated cells. Data information: data are presented as mean values + SD for six replicates (n=6). The p-value (Student's t-test) is indicated, **<0.01, ***<0.005 and ns=non-significant",
    "ncbi_link": "GATA6: 2627"
  },
  {
    "caption": "C-D.  MM099 (c) and  MM029 (d) were pre-treated with either siCTL or siABCG2 as indicated and treated with increasing concentrations of THZ1 for 72h. Mean growth is shown relative to vehicle (DMSO)-treated cells. E-F. MM099 (e) and MM029 (f) were pre-treated with either siCTL or siABCG2 as indicated and treated with increasing doses  of Vemurafenib for 72h. Mean growth  is shown relative to vehicle (DMSO)-treated cells. D Data information: data are presented as mean values + SD for three replicates (n=3). IC50 for each cell line is indicated.",
    "ncbi_link": "ABCG2: 9429"
  },
  {
    "caption": "C-E. qRT-PCR  analysis showing average  TBP-normalized fold expression of MITF (C), SOX10 (D) and GATA6 (E) in 501mel treated either with DMSO/THZ1 (50nM) (upper) or DMSO/JQ1  (10μM) (lower) for 24h. Data information: data are presented as mean values + SD for six replicates (n=6). The p-value (Student's t-test) is indicated, *<0.05.",
    "ncbi_link": "GATA6: 2627
MITF: 4286
SOX10: 6663
TBP: 6908"
  },
  {
    "caption": "A. qRT-PCR analysis showing average TBP-normalized fold expression of SOX10, MITF and GATA6 in 501mel  treated with either siCTL or siSOX10 for 48h. Data information: , data are presented as mean values + SD for six replicates (n=6). The p-value (Student's t-test) is indicated, *<0.05.",
    "ncbi_link": "GATA6: 2627
MITF: 4286
SOX10: 6663
TBP: 6908"
  },
  {
    "caption": "D. MM099MITF-SOX10-PAX3 expressing inducible  MITF-SOX10-PAX3  genes was treated or not with Doxycycline (1μg/ml) for 24h and protein lysates were immuno-blotted  for the indicated protein. The numbers below the gel lanes represent relative protein level, which was determined from the band intensity  using ImageJ software, and normalized relative to VINCULIN.",
    "ncbi_link": "MITF: 4286
PAX3: 5077
SOX10: 6663"
  },
  {
    "caption": "E. qRT-PCR  analysis showing average TBP-normalized fold expression of GATA6, ABCG2, AMIGO2 or  SERPINE1  in  MM099MITF-SOX10-PAX3 treated or not with Doxycycline (1μg/ml) for 24h. Data information: data are presented as mean values + SD for three biological triplicates. The p-value (Student's t-test) is indicated, *<0.05, **<0.01; ***<0.001.",
    "ncbi_link": "ABCG2: 9429
AMIGO2: 347902
GATA6: 2627
MITF: 4286
PAX3: 5077
SERPINE1: 5054
SOX10: 6663
TBP: 6908"
  },
  {
    "caption": "D-E. Graphs showing the average  expression of GATA6 (d) and MITF (e) (RPKM) for each phenotype cluster in T0 (drug naïve) (blue), phases 1-2 (MDR) (green and yellow) and phase 3 (drug-resistance) (red). Data information: data are presented as mean values + SEM (n=6,574 cells from 5 PDX).",
    "ncbi_link": "GATA6: 2627
MITF: 4286"
  },
  {
    "caption": "A. Rab25 expression decreases nutrient withdrawal (24 h) induced cell death in ovarian A2780 and IOSE29 cells measured using the Cell death ELISA plus assay (left); cells were cultured in complete media (containing 5% FBS), serum free media (SF), complete media plus 2DG, serum and glucose free media (SF-glu), or in amino acid, glucose and SF Earls buffer salt solution (EBSS). (a) p < 0.01 versus control and (b) p < 0.05 versus pcDNA. (Right) Percentage of apoptotic cells (sub-G0 population) by flow cytometry in A2780 cells following glucose and serum withdrawal (Glu/SF). (a) p < 0.001 versus A2780pcDNA control and (b) p < 0.05 A2780Rab25 versus A2780pcDNA control.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "B. Decreasing Rab25 expression increases sensitivity to nutrient stress induced cell death. Expression of Rab25 was down-regulated by siRNA or shRNA specific to Rab25.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "C. Rab25 regulates autophagy activity in ovarian cancer cells under serum and glucose deprivation conditions. Western blot for the 16kD LC3-II fragment, indicative of autophagy activity, in A2780 cells after 4 and 6 h of serum and glucose withdrawal.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "E-H. Expression of Rab25 decreases glucose and serum deprivation induced signalling activation. Protein expression was measured by RPPA or WB analysis.E. RPPA detection of time-dependent activation of AMPK after nutrient withdrawal.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "E-H. Expression of Rab25 decreases glucose and serum deprivation induced signalling activation. Protein expression was measured by RPPA or WB analysis.F. WB analysis of AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in HEY ovarian cancer cells (upper panel). WB of phospho-ACC levels in A2780, IOSE80ht and SKOV3 ovarian cells after 1 h of nutrient withdrawal (lower panel).",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "E-H. Expression of Rab25 decreases glucose and serum deprivation induced signalling activation. Protein expression was measured by RPPA or WB analysis.G. RPPA detection of phosphorylation of ACC after withdrawal of serum and glucose.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "E-H. Expression of Rab25 decreases glucose and serum deprivation induced signalling activation. Protein expression was measured by RPPA or WB analysis.H. Effect of Rab25 down-regulation on AMPK (left panel) and ACC (right panel) phosphorylation. Total cellular protein, isolated from A2780pcDNA and Rab25 expressing cells 72 h post-transfection with either non-target (NT) RNAi or Rab25 specific RNAi, was separated by polyacrylamide gel electrophoresis (PAGE) followed by WB analysis. (a) p < 0.001 versus NT RNAi control and (b) p < 0.001, pcDNA versus Rab25.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Expression of Rab25 increases endogenous ATP level in ovarian cancer cells. *p < 0.001 Rab25 versus pcDNA. The mean cellular concentration of ATP per mg of protein (based on the standard curve generated using a known amount of ATP) is 2.36−10 moles/mg for IOSE29htpcDNA cells, 6.21−10 moles/mg for IOSE29htRab25 cells, 8.14−11 moles/mg for IOSE80htpcDNA cells, 1.05−10 moles/mg for IOSE80htRab25 cells, 2.85−10 moles/mg for A2780pcDNA cells, 3.81−10 moles/mg for A2780Rab25 cells, 7.23−10 moles/mg for HEYpcDNA cells and 9.82−10 moles/mg for HEYRab25 cells.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Rab25 expression increases ATP synthesis and delays fall in total cellular ATP levels after glucose and serum withdrawal, p < 0.001 Rab25 versus control pcDNA.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Down-regulation of Rab25 expression decreases ability to maintain ATP after glucose and serum withdrawal (a) p < 0.05 SF-Glu versus FBS and (b) p < 0.05 versus control.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Expression of Rab25 increases total cellular glycogen content while down-regulation of Rab25 expression decreases total cellular glycogen content (µg of glycogen/mg protein). Cells were cultured in complete media for 24 h before glycogen measurement. (a) p < 0.01 Rab25 versus pcDNA, (b) p < 0.05 Rab25 RNAi versus NT RNAi and (c) p < 0.05 shRAb25 versus shRNA control.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Decrease in cellular glycogen content after glucose and serum withdrawal *p < 0.001 Rab25 versus pcDNA.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Effect of GPi (Bay U6571) and oligomycin on ATP production. A2780pcDNA transfected and Rab25 expressing cells were pretreated with vehicle (control), 30 µM of Bay U6571 (GPi) or 25 µg/ml of oligomycin for 2 h. Cells were then cultured in serum- and glucose free RPMI 1640 in the presence or absence of Bay U6571 or oligomycin for the indicated times. (a) p < 0.01 oligomycin time 0 versus control time 0 and (b) p < 0.01 versus time 0 at each treatment group.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Down regulation of Rab25 expression and inhibition of glycogen breakdown by GPi administration increases 2DG induced cell death *p < 0.05 versus shRNA control.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "A. Rab25 expression increases phospho but not total AKT and GSK3 levels in A2780 cells leading to decreased phosphorylation of GS (pGS).",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "C. Inhibition of GSK3 activity increases total cellular glycogen levels. pcDNA transfected and Rab25 expressing ovarian cancer cells were cultured in complete media in the presence of 10 µM GSK3i for the indicated times. Total cellular glycogen content was measured and normalized with total protein content. (a) p < 0.001 versus no GSK3i treated pcDNA cells.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "D-E. Effect of PI3K inhibitor PI103 on cellular glycogen content and ATP production. Ovarian cancer cells were pretreated with PI103 for at least 2 h in complete media. Cells were then subjected to 2 hglucose and FBS withdrawal to deplete endogenous glycogen followed by culturing cells in RPMI-glucose media in the presence of PI103 for 2 h (2 hSF). After 2 h of nutrient stress, complete media containing PI103 was added to the cells for 30 min (5% FBS) for recovery. A second glucose and FBS withdrawal (15 min SF) followed immediately to examine the effect on glycogen and ATP levels. a, p < 0.001 5% FBS versus 2 hSF, b, p < 0.01 15 min SF versus 5% FBS.E. Utilization of glycogen to produce ATP.",
    "ncbi_link": "PI3K: 5290///5291///5294///5293"
  },
  {
    "caption": "F. Addition of AKT inhibitor MK2206 (AKTi) abolishes Rab25-dependent glycogen storage. (a) p < 0.05 versus shRNA control and (b) p < 0.01 SF + AKTi versus SF.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "G. Inhibiting AKT pathway and glucose metabolism decreases cell viability. Cells were pretreated with 10 µM of PI103 or AKTi, 100 µM LND or 3BrPy for 2 h before switching to SF media in the presence of inhibitors for an addition16 h before cell titre blue viability assay. *p < 0.001 shRNA Rab25 versus shRNA control.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "A. Rab25 over-expression increases H3-labelled 2DG uptake. (a) p < 0.001 Rab25 versus pcDNA. Results are mean ± s.d. of a triplicate in one of representative experiment.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "B. Down-regulation of Rab25 or AKT expression, or inhibition AKT activity by MK2206 decreases glucose uptake in HEY cells (a) p < 0.001 versus NT siRNA control, (b) p < 0.05 versus siRab25 and (c) p < 0.05 versus siAKT.",
    "ncbi_link": "AKT: 207
Rab25: 57111"
  },
  {
    "caption": "C. Effect of down regulation of Rab25 and AKT inhibitor MK2206 (AKTi) on glucose uptake. Cells were either pretreated for 2 h with AKTi before assessing glucose uptake. (a) p < 0.05 versus shRNA control and (b) p < 0.05 versus shRab25.",
    "ncbi_link": "AKT: 207
Rab25: 57111"
  },
  {
    "caption": "E-G. Resistance to 2DG induced cell death in Rab25 cells is mediated through the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway was achieved by addition of 10 µM of PI103 or MK2206.E. AKT inhibition increases sensitivity to 2DG induced cell death. *p < 0.001 versus HEYpcDNA cells.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "E-G. Resistance to 2DG induced cell death in Rab25 cells is mediated through the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway was achieved by addition of 10 µM of PI103 or MK2206.F. Down-regulation of AKT by siRNA specific to AKT.",
    "ncbi_link": "AKT: 207
Rab25: 57111"
  },
  {
    "caption": "E-G. Resistance to 2DG induced cell death in Rab25 cells is mediated through the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway was achieved by addition of 10 µM of PI103 or MK2206.G. Or down-regulation of Rab25 by shRNA specific to Rab25 enhances 2DG induced cell death. *p < 0.001 versus RNAi control cells.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Ovarian cancer HEY cells (upper panel) were co-transfected with AKT-IFPN and Rab25-IFPC or with AKT-IFPC and Rab25-IFPN. Cells become fluorescent due to an interaction between AKT and Rab25 bringing the two halves of the fluorescent protein into proximity creating a stable complex and restoring fluorescence. Hela cells stably expressing AKT-IFPN (lower panel) were transfected with Rab25-IFPC or PDK-IFPC as control. A brightfield image corresponding to the fluorescent image is shown and transfected cells indicated by an arrow.",
    "ncbi_link": "AKT: 207
PDK: 5170
Rab25: 57111"
  },
  {
    "caption": "Detection of Rab25 and AKT interaction by immunoprecipitation. Ovarian cells expressing HA-tagged Rab25 were IP with anti-HA antibody. The resultant complex was separated by gel electrophoresis and detected by WB using anti-AKT antibody.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Generation of Rab25 deletion mutants. Expression of the deletion mutants was detected by immunofluorescence staining (upper panel) and WB (middle panel) using anti-GFP antibody which interacts with YFP. Diagrammatic representation of the structure of the mutants is shown in the lower panel.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Rab25 deletion mutants do not alter cellular glycogen and ATP levels. Ovarian cancer cell lysates were collected 24 h post transfection. (a) p < 0.05 versus empty vector transfected cells.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "A. Rab25 expression correlates with glycogen levels in patienttumours. Total RNA and total cellular extracts, isolated from 31 ovarian cancer patient specimens, were subjected to Rab25 gene expression and glycogen content analysis using qPCR and glycogen assay, respectively.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "B-C. The Rab25 expression signature identifies patients with a poor prognosis. Ovarian cancer patients were classified as either mirroring the Rab25-associated gene expression signature (Rab25 signature) or not (non-Rab25 signature) using linear discriminant analysis in BRB tools, in two independent published ovarian datasets. Progression free survival curvesfor patients with advanced disease (Stage II to IV) are shown. Univariate analyses were plotted using Kaplan-Meier method and Coxplots used for multivariate analyses (co-variates included stage, grade, histology and residual disease).B. Tothill et al, 2008.C. Dressman et al, 2007.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "D. Prediction of breast cancer overall survival in two independent published breast datasets (upper panel) Pawitan et al, 2005 and (lower panel) Chin et al, 2006, based on Rab25-associated gene signature. Breast patient classification was determined by BRB tool class prediction function to identify patient with Rab25-associated gene expression signature (Rab25-signature) or without (non-Rab25 signature). All patients from the datasets were included in class prediction.",
    "ncbi_link": "Rab25: 57111"
  },
  {
    "caption": "Sashimi plots of representative SRSF3-dependent exons. C2C12 cells were treated with control siRNA (siCont), Srsf3 siRNA (siSrsf3), Hnrnpk siRNA (siHnrnpk), or both Srsf3 and Hnrnpk siRNAs (siSrsf3+siHnrnpk), and RNA-seq was performed. Lines indicate junction-spanning reads. Gene structures are shown below the Sashimi plots.",
    "ncbi_link": "Hnrnpk: 15387
Srsf3: 20383
SRSF3: 20383"
  },
  {
    "caption": "mRNA expression levels of seven CPSF factors in C2C12 cells treated with the indicated siRNA normalized for those treated with the control siRNA. **p < 0.01 by CuffDiff (Trapnell et all., 2010).",
    "ncbi_link": "CPSF: 94230"
  },
  {
    "caption": "SRSF3-responsive alternative 3′ ends of the Med1 gene. (Top panel) Disorder analysis for MED1 using PONDR VL-XT (deep blue) and IUPred2 (light blue). The scores in the ordinate indicate disordered tendencies between 0 and 1 (a score of more than 0.5 indicates disordered). (Middle panel) Protein and gene structures of MED1. The protein structure was segmented into individual exonic regions. The SRSF3-responsive last exon is indicated in pink. (Bottom panel) Sashimi plots of RNA-seqs from Srsf3- and/or Hnrnpk-silenced cells.",
    "ncbi_link": "Hnrnpk: 15387
Med1: 19014
MED1: 19014
SRSF3: 20383
SRSF3: 6428
Srsf3: 20383"
  },
  {
    "caption": "Immunofluorescence images of MED1 in C2C12 cells treated with siCont (C), siSrsf3 (S), siHnrnpk (K), or siSrsf3+siHnrnpk (S+K). A white dotted contour outlines the nucleus. Box plots (right) show quantification of nuclear (NUC) and cytoplasmic (CYT) localization of MED1. The average intensity of one nucleus or a cytoplasmic segment is individually plotted.",
    "ncbi_link": "Hnrnpk: 15387
Srsf3: 20383"
  },
  {
    "caption": "The intrinsically disordered region (IDR) in MED4. Disorder analysis, protein and gene structures, and Sashimi plots are shown in (B). Splicing of these genes was not affected by the siRNA treatment.",
    "ncbi_link": "MED4: 67381"
  },
  {
    "caption": "
 (A) Stopped-flow assay measuring relative rates of lactic acid transport into reconstituted vesicles containing wild-type or mutant transporter (green, control with empty vesicles; red, wild-type; blue, K35A; cyan, F90A; magenta, F94A; yellow, K177A; olive green, H230A; and gray, H230N). (B) Relative rates of lactic acid transport based on reswelling rates of proteoliposomes. Each data point is an average of five different light scattering data sets. Error bars depict standard deviation for these five light scattering data. All of the transport rates from the mutant transporters are significantly different compare from that of wild-type PfFNT (K35A, P = 2.8 x 10-3; F90A, P = 4.4 x 10-7; F94A, P = 4.9 x 10-6; K177A, P = 1.2 x 10-3; H230A, P = 4.5 x 10-7; H230N, P = 2.0 x 10-6; student's t-test) (green, control with empty vesicles; red, wild-type; blue, K35A; cyan, F90A; magenta, F94A; yellow, K177A; olive green, H230A; and gray, H230N). 
",
    "ncbi_link": "PfFNT: 814480"
  },
  {
    "caption": "Human red blood cells (RBCs) were incubated with 400 nM pigment or control ΔcylE extract, and kinetics of K+ and Hb release was monitored. Data shown are the average and SEM of six independent experiments. The time to 50% K+ and 50% Hb release with pigment was 4.8 min and 8.4 min, respectively; n = 6, P < 0.0001, extra sum-of-squares F test.",
    "ncbi_link": "cylE: 1013473"
  },
  {
    "caption": "Characteristics of membrane permeabilization by the GBSpigment in artificial lipid bilayers. Lipid bilayers were generated using diphytanoylphosphatidylcholine (DPhPC) and treated with either 2 μM pigment or an equivalent amount of the control ΔcylE extract. In the pigment-treated sample, channel conductance indicating disruption of the membrane is seen within 45 s. Erratic and non-discrete fluctuations in current are observed, suggesting the formation of multiple, small membrane defects. The bilayer eventually breaks at 120 s. In lipid bilayers treated with the control ΔcylE extract, the mean ionic current trace remains constant at 0 pA, showing no membrane disruption. Data shown are representative of three independent experiments.",
    "ncbi_link": "cylE: 1013473"
  },
  {
    "caption": "A, B PBMC-derived macrophages were treated with GBS WT, ΔcylE, ΔcovR, or ΔcovRΔcylE at an MOI of 1 and incubated for 4 h. Cytotoxicity was measured by LDH release (A), and IL1β release in supernatants was measured by ELISA (B).Data information: Data shown are the average of four independent experiments performed in triplicate, error bars ± SEM. Significance was determined using Bonferroni's multiple comparison test following ANOVA. (A) n = 4, *P = 0.021 for WT versus ΔcovR; *P = 0.01 for ΔcovR versus ΔcovRΔcylE. (B) n = 4, *P = 0.031 for WT versus ΔcovR; *P = 0.036 for ΔcovR versus ΔcovRΔcylE. (C) n = 4, ****P < 0.0001, **P = 0.002. (D) n = 4, **P = 0.005.",
    "ncbi_link": "covR: 
cylE: 1013473"
  },
  {
    "caption": "C, D PBMC-derived macrophages primed with 100 ng/ml LPS for 3 h were incubated with various concentrations of GBSpigment or control ΔcylE extract for 4 h. Cytotoxicity was measured by alamar blue assay (C), and IL1β release from pigment- or ΔcylE extract-treated cells was measured by Luminex assay (D). (C) n = 4, ****P < 0.0001, **P = 0.002. (D) n = 4, **P = 0.005.",
    "ncbi_link": "cylE: 1013473"
  },
  {
    "caption": "A, B WT THP-1macrophages were treated with GBS WT, ΔcylE, ΔcovR, or ΔcovRΔcylE at an MOI of 1 and incubated for 4 h. Cytotoxicity was measured by LDH release (A), and IL1β release in supernatants was measured by Luminex assay (B).Data information: Data from three independent experiments performed in triplicate are shown, error bars ± SEM. Significance was determined using Bonferroni's multiple comparison test following ANOVA. (A) n = 3, **P = 0.0080 for WT versus ΔcovR; **P = 0.0016 for ΔcovR versus ΔcovRΔcylE. (B) n = 3, *P = 0.03 for WT versus ΔcovR; *P = 0.02 for ΔcovR versus ΔcovRΔcylE. (C) n = 3, ****P < 0.0001. (D) n = 3, *P = 0.01.",
    "ncbi_link": "covR: 
cylE: 1013473"
  },
  {
    "caption": "C, D WT THP-1macrophages were incubated with various concentrations of GBSpigment or control ΔcylE extract for 4 h. Cytotoxicity was measured by alamar blue assay (C), and IL1β release from pigment- or ΔcylE extract-treated cells was measured by Luminex assay (D).(C) n = 3, ****P < 0.0001. (D) n = 3, *P = 0.01.",
    "ncbi_link": "cylE: 1013473"
  },
  {
    "caption": "A, B THP-1macrophages transfected with empty vector, scrambled control, shASC, or shNLRP3 were treated with GBS WT, ΔcylE, ΔcovR, or ΔcovRΔcylE at an MOI of 1 and incubated for 4 h. Cytotoxicity was measured by LDH release (A), and IL1β release in supernatants was measured by Luminex assay (B). Data from three independent experiments performed in triplicate are shown.Data information: Data were analyzed using Bonferroni's multiple comparison test following ANOVA, error bars ± SEM. (A) n = 3, for WT: **P = 0.001 (vector versus shNLRP3), **P = 0.0016 (vector versus shASC); for ΔcovR: ***P = 0.0008 (vector versus shNLRP3), ***P = 0.0001 (vector versus shASC), *P = 0.047 (scrambled versus shNLRP3), **P = 0.0054 (scrambled versus shASC). Data obtained from THP-1/vector was not significantly different from THP-1/scrambled, P = 0.18. (B) n = 3, *P = 0.025. Data obtained from THP-1/vector were not significantly different from THP-1/scrambled, P = 0.89.",
    "ncbi_link": "covR: 
cylE: 1013473
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "C, D The shRNA THP-1macrophages were incubated with various concentrations of GBSpigment or ΔcylE extract for 4 h. Cytotoxicity was measured by alamar blue assay (C), and IL1β release in supernatants was measured by Luminex assay (D). Pigment-mediated cytotoxicity is dependent on the NLRP3 inflammasome components, suggesting that pigment is inducing a programmed cell death. Data shown are the average of at least three independent experiments performed in triplicate.Data information: Data were analyzed using Bonferroni's multiple comparison test following ANOVA, error bars ± SEM. (C) n = 3, for 4 μM pigment: **P = 0.0063 (vector versus shNLRP3), **P = 0.0035 (vector versus shASC), *P = 0.01 (scrambled versus shNLRP3), **P = 0.009 (scrambled versus shASC); for 2 μM pigment: **P = 0.0088 (vector versus shNLRP3), **P = 0.0066 (vector versus shASC), *P = 0.01 (scrambled versus shNLRP3 or shASC); for 1 μM pigment: *P = 0.02 (vector versus shNLRP3), *P = 0.01 (vector versus shASC). Data obtained from THP-1/vector were not significantly different from THP-1/scrambled, P = 0.99. (D) n = 3, ****P < 0.0001, *P = 0.015.",
    "ncbi_link": "cylE: 1013473
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "A, B THP-1macrophages proficient for NLRP3 (transfected with scrambled control, A) or deficient for NLRP3 (shNLRP3, B) were treated with 1 μM pigment or ΔcylE extract for 20 min, and propidium iodide (PI) was added during the final 10 min. PI uptake was measured by flow cytometry, and data shown are representative of two independent experiments.",
    "ncbi_link": "cylE: 1013473
NLRP3: 114548"
  },
  {
    "caption": "C, D Intracellular potassium concentration was measured by ICP-AES. THP-1macrophages transfected with the scrambled control (C) or shNLRP3 (D) were treated with GBSpigment (1 μM) or an equivalent amount of the ΔcylE extract. At various time points, cells were lysed and intracellular [K+] was measured relative to untreated cells (see bars and left y-axis), and percent cell death was quantified by alamar blue (see squares, dotted connecting lines and right y-axis). Both NLRP3-proficient and NLRP3-deficient macrophages initially lose intracellular K+ due to GBSpigment (compare t = 0 min to t = 30 min), but the NLRP3-deficient cells (shNLRP3) are able to recover, while the scrambled control do not, demonstrating that initial K+ loss occurs independently of NLRP3. Data are average of three independent experiments performed with independent pigment preparations in triplicate and were analyzed using Dunnett's multiple comparison test following ANOVA; all data were compared to control at t = 0, error bars ± SEM. (C) n = 3, ***P = 0.0002, *P = 0.019, **P = 0.0032 for 120 min, **P = 0.0072 for 180 min. (D) n = 3, **P = 0.0043, *P = 0.031.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "THP-1macrophages were treated with GBSpigment, and caspase 1 activation was measured by flow cytometry using a FLICA reagent. Pigment treatment of the scrambled shRNA control cell line induces more caspase 1 activation compared to the shNLRP3cell line, demonstrating that the pigment activates caspase 1 exclusively through the NLRP3 inflammasome. Results are representative of three independent experiments.",
    "ncbi_link": "NLRP3: 114548"
  },
  {
    "caption": "In utero fetal death in wild-type CD-1mice due to infection with GBS WT, hyperhemolytic ΔcovR, and non-hemolytic ΔcovRΔcylE. Fetal death is represented by the number of dead fetuses/total number of fetuses obtained from six pregnant mice per group. 'n' indicates total number of pups (both live and dead); ****P < 0.0001, Fisher's exact test.",
    "ncbi_link": "covR: 
cylE: 1013473"
  },
  {
    "caption": "Fetal death due to infection with hyperhemolytic GBS ΔcovR and non-hemolytic ΔcovRΔcylE in WT C57BL6 and NLRP3 inflammasome-deficient mice; fetal death is represented by the number of dead fetuses/total number of fetuses obtained from 6 pregnant mice per group. 'n' indicates total number of pups (both live and dead); *P = 0.011, **P = 0.0015, ****P < 0.0001, Fisher's exact test. Fetal death due to ΔcovRΔcylE in WT C57BL6 and NLRP3KO mice was not significant and is indicated as NS; P = 0.31, Fisher's exact test.",
    "ncbi_link": "covR: 
cylE: 1013473
NLRP3: 216799"
  },
  {
    "caption": "Female pregnant wild-type (CD-1, C57BL6) or NLRP3-deficient mice were injected in utero with 106-7CFU of GBS WT, ΔcovR, or ΔcovRΔcylE and monitored for preterm birth. Surgery and GBS inoculation for each pregnant mouse were performed independently. Data shown are representative of experiments with 6 animals per group for each GBS strain and two animals were used for saline controls.Bacterial burden in fetal pups and uterine horns from mice infected with the various GBS strains (n = 6/pup; of note, pups that were delivered preterm were excluded from CFU enumeration. Scheme of pup numbering is shown in (A). RUH and LUH indicate right uterine horn and left uterine horn, respectively. CFUs are not significantly different between any of the groups (ANOVA, P = 0.6, error bars ± SEM).",
    "ncbi_link": "covR: 
cylE: 1013473
NLRP3: 216799"
  },
  {
    "caption": "Female pregnant wild-type (CD-1, C57BL6) or NLRP3-deficient mice were injected in utero with 106-7CFU of GBS WT, ΔcovR, or ΔcovRΔcylE and monitored for preterm birth. Surgery and GBS inoculation for each pregnant mouse were performed independently. Data shown are representative of experiments with 6 animals per group for each GBS strain and two animals were used for saline controls.IL-1β levels in GBS-infected tissues (placenta and fetus, n = 6/group) was measured by Luminex assay (*P = 0.025, ***P = 0.0002, ****P < 0.0001, Bonferroni's multiple comparison test following ANOVA). IL-1β levels was not significantly different in NLRP3KO mice infected with ΔcovR compared to NLRP3KO mice infected with ΔcovRΔcylEmice and is indicated as NS; P = 0.99.",
    "ncbi_link": "covR: 
cylE: 1013473
NLRP3: 216799"
  },
  {
    "caption": "B Analysis of anti-Bax and anti-Bak antibody specificity using whole cell lysates from HCT116 wild-type, Bax KO, Bak KO and Bax/Bak DKO. After detection of Bax the membrane was redecorated with anti-Bak antibodies (Bax/Bak). Actin is used as loading control.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "A Confocal images of HCT116 Bax/Bak DKO cells transfected with GFP-Bak in the absence (left) or the presence (right) of Bcl-xL overexpression. Scale bar 15 µm. n ≥ 10.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "B FLIP (Fluorescence Loss in Photobleaching) of mitochondrial GFP-Bak in the absence (●, straight line) or the presence (○, broken line) of overexpressed Bcl-xL. Fluorescence of the neighboring cell (in Fig. 2C) is shown as control (, dotted line). Data represent averages ± SEM from 16 (-Bcl-xL) and 40 (+Bcl-xL) ROI measurements.",
    "ncbi_link": "Bcl-xL: 598"
  },
  {
    "caption": "A Western blot analysis of GFP-Bak localization in cytosol (C) and heavy membrane fraction (HM) of HCT116 Bax/Bak DKO cells with or without overexpressed wild-type Bcl-xL or Bcl-xL G138A. GAPDH and Tom20 serve as fractionation controls. n = 10. Bak shuttling by Bcl-xL is independent of the GFP fusion (Fig. E2a).B Quantification of predominant mitochondrial localization (light grey bars) and mixed cytosolic and mitochondrial localization (dark grey bars) of Bak in HCT116 Bax/Bak DKO cells expressing GFP-Bak with or without Bcl-xL overexpression. Data represent averages ± SD from 3 independent experiments with n ≥ 100.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "C Retrotranslocation rates measured for wild-type Bak or Bak D83R in the presence or the absence of Bcl-2, Mcl-1, wild-type Bcl-xL or Bcl-xL G138A. Data represent averages ± SD.",
    "ncbi_link": "Bak: 578
Bcl-2: 596
Bcl-xL: 598
Mcl-1: 4170"
  },
  {
    "caption": "D Analysis of endogenous Bak localization in cytosol (C) and heavy membrane fraction (HM) of HeLa cells expressing degradation-prone DD-FLAG-Bcl-xL. In the absence of Shield-1 DD-FLAG-Bcl-xL is readily degraded, resulting in unaltered Bcl-xL levels. Addition of 0.5 µM Shield-1 instantly stabilizes DD-FLAG-Bcl-xL resulting in elevated Bcl-xL levels that increase cytosolic levels of endogenous Bak (Fig. E3C, D). Akt1 and Tom20 serve as fractionation controls. n = 3.",
    "ncbi_link": "Bcl-xL: 598"
  },
  {
    "caption": "B Quantification of HCT116 Bax/Bak DKO cells expressing Bax, BaxTBak, BakTBax or Bak with the expressed protein being present largely cytosolic (white bars), in a mixed distribution between cytosol and mitochondria (grey bars) or largely mitochondrial (black bars). Data represent averages ± SEM from 7 independent experiments with n ≥ 100 cells.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "C Confocal images of HCT116 Bax/Bak DKO cells expressing Bax, BaxTBak, BakTBax or Bak. The GFP/YFP fluorescence of the expressed protein variants is depicted in the top panels and in green in the merged image on the bottom. The mitochondria were stained by MitoTracker far red depicted in red in the merged images (bottom row). Scale 10 µm. n ≥ 5.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "D Western blot analysis of Bax, BaxTBak, Bak and BakTBax localization expressed in HCT116 Bax/Bak DKO cells. Cytosol (C) and heavy membrane fraction (HM) of HCT116 Bax/Bak DKO cells are displayed. GAPDH and VDAC serve as fractionation controls. n = 3.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "A Caspase 3/7 activity measured in HCT116 Bax/Bak DKO cells overexpressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression in the absence of apoptosis stimuli. Caspase activity is displayed in relative fluorescence units (RFU). pcDNA3.1-transfected cells served as control. Data represent averages ± SEM. n ≥ 3. p-values according to One Way ANOVA are displayed.B Staurosporine (STS, 1 µM)-induced caspase 3/7 activity of Bax/Bak DKO cells overexpressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression displayed in relative fluorescence units (RFU). Data represent averages ± SEM. n ≥ 3. p-values according to One Way ANOVA. BaxTBak activities with and without Bcl-xL expression revealed no significant difference (n.s.), while in the presence of Bcl-xL overexpression BaxTBak activity is significantly higher than Bax, Bak or BakTBax activities (p < 0.001).",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "C Analysis of the active Bax conformation in HCT116 Bax/Bak DKO cells expressing wild-type Bax or BaxTBak with (dark grey bars) or without Bcl-xL overexpression (light grey bars) by the monoclonal antibody 6A7 (Sigma) detecting the active Bax protein fold by fluorescence imaging. Cells were analyzed prior or after treatment with 1 µM STS in the presence of the pan-caspase inhibitor qVD. Data are represented as % of the expressing cell population ± SEM. n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "D HCT116 Bax/Bak DKO cells ectopically expressing wild-type Bax or BaxTBak with (dark grey bars) or without Bcl-xL (light grey bars) were analyzed in the presence or the absence of 1 µM STS and qVD for retained mitochondrial cyt c. Data are represented as % of the expressing cell population ± SEM. n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "E Flow cytometry analysis of Annexin V-staining of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax in the absence (red line) or the presence of Bcl-xL overexpression (black line), following STS-treatment. The percentage of gated cells is displayed in the color of the corresponding graph. Data represent averages ± SD. n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "F Colony formation of Bax/Bak DKO cells transfected with pcDNA, Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression. STS (1 µM) was added for 24 hrs before cells were replated and colonies were stained with methylene blue typically 14 days after treatment.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "G Quantification of colony formation of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax with or without Bcl-xL overexpression after STS treatment (Fig. 5F). Data represent averages ± SEM. n = 4. p-values according to One Way ANOVA. BaxTBak expressing cells with or without Bcl-xL expression showed no significant difference (n.s.).H Quantification of the colony formation of Bax/Bak DKO cells expressing Bax, BaxTBak, Bak or BakTBax in presence of Bcl-xL overexpression without apoptosis stimulation. Data represent averages ± SEM. n = 5. p-values according to One Way ANOVA.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "A FLIP of BaxTBakSS without (○, broken line) or with (●, straight line) overexpressed Bcl-xL. Fluorescence of a neighboring cell is shown as control (, dotted line). Data represent averages ± SEM from 20 (-Bcl-xL) and 16 (+Bcl-xL) ROI measurements.",
    "ncbi_link": "Bak: 578
Bcl-xL: 598"
  },
  {
    "caption": "B Western blot analysis of PARP cleavage in HCT116 Bax/Bak DKO cells overexpressing Bax, Bax S184V, BaxTBak or BaxTBak V197/198S. The experiment was carried out in the absence of apoptotic stimuli. Cells transfected with pcDNA3.1 vector serve as control for PARP cleavage. Similar sample loading is controlled by actin. n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "C Colony formation of Bax/Bak DKO cells transfected with pcDNA, BaxTBak or BaxTBakSS with Bcl-xL overexpression in the absence of apoptotic stimuli. n = 3.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "D Caspase 3/7 activity was measured in HCT116 Bax/Bak DKO cells overexpressing Bax, Bax S184V, BaxTBak or BaxTBak V197/198S. Caspase activity is displayed in relative fluorescence units (RFU). The experiment was carried out in the absence of apoptotic stimuli and pcDNA3.1-transfected cells served as control. Data represent averages ± SEM. n = 4. p-values according to One Way ANOVA using the Holm-Sidak method are displayed.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "F STS-induced caspase 3/7 activity of HCT116 Bax/Bak DKO cells expressing Bax, Bax S184V, BakTBax or BakTBax S184V is displayed normalized to Bax activity. Data represent averages ± SEM. n ≥ 3.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "G Western blot analysis of PARP cleavage after STS treatment in HCT116 Bax/Bak DKO cells overexpressing Bax, Bax S184V, BakTBax or BakTBax S184V. Empty vector-transfected cells serve as control for PARP cleavage and actin is the loading control. n = 3.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "A Carbonate extraction of the HM protein fraction of Bax/Bak DKO cells expressing wild-type Bcl-xL in the presence or the absence of Bak or Bax analyzed by Western blot. Carbonate extractable supernatant (S) and membrane-integral protein pellet (P) are displayed. Smac is released from the IMS during carbonate extraction and VDAC remains in the pellet. n = 4.B Western blot analysis of Bcl-xLTBax carbonate extraction from the heavy membrane fraction from Bax/Bak DKO cells expressing the Bcl-xL variant with or without Bak or Bax. Smac and VDAC serve as controls for supernatant (S) and pellet (P). n = 4.C Carbonate extraction of the HM protein fraction of Bax/Bak DKO cells expressing Bcl-xL G138A with or without Bak or Bax. Smac and VDAC serve as controls for supernatant (S) and pellet (P). n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581
Bcl-xL: 598"
  },
  {
    "caption": "D HM protein fraction and carbonate extraction of Bax/Bak DKO cells expressing Bax, BaxTBak or Bax S184V. Smac and VDAC serve as controls for supernatant (S) and pellet (P). n = 4.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "E Smac release from the heavy membrane fraction (HM) into the cytosol (C) in HCT116 Bax/Bak DKO cells overexpressing Bax and BaxTBak without apoptotic stimuli analyzed by Western blot. Bax and BaxTBak were expressed differentially to produce similar levels of mitochondrial Bax. GAPDH and Tom20 serve as fractionation controls. n = 3.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "F PARP cleavage in HCT116 Bax/Bak DKO cells expressing similar levels of mitochondrial Bax or BaxTBak analyzed by Western blot without apoptotic stimuli. Actin is used as loading control. n = 3.",
    "ncbi_link": "Bak: 578
Bax: 581"
  },
  {
    "caption": "(A) BH3‐only BIK displaces a subset of BCL‐2 complexes at the ER. Purified LM from H1299 HA‐BCL‐2b5 cells either mock infected or infected with Ad‐BIKb5 was subjected to cross‐linking with BMH and visualized by immunoblot. Asterisks (*) denote BCL‐2 cross‐linked products, which are displaced by BIK. Bold arrow denotes region containing cross‐linked NAF‐1/BCL‐2.",
    "ncbi_link": "BCL‐2: 596
BIK: 638"
  },
  {
    "caption": "(D) Endogenous NAF‐1 cross‐links with BCL‐2 at the ER. LM purified from H1299 neo and HA‐BCL‐2b5 cells were subjected to cross‐linking by BMH and immunoprecipitation with anti‐NAF‐1 antibody. Precipitates were analysed by immunoblot with anti‐BCL‐2.",
    "ncbi_link": "BCL‐2: 596"
  },
  {
    "caption": "(E) NAF‐1 is displaced from BCL‐2 by BH3‐only BIK. H1299 HA‐BCL‐2b5 cells were either mock infected or infected with Ad‐BIK. Purified LM was treated as in (D).",
    "ncbi_link": "BCL‐2: 596
BIK: 638"
  },
  {
    "caption": "(C) Co‐immunoprecipitation of NAF‐1‐Flag and HA‐BCL‐2b5. Lysates from H1299 HA‐BCL‐2b5 cells infected with Ad‐NAF‐1‐Flag were collected and treated as in (A).",
    "ncbi_link": "BCL‐2: 596
NAF‐1: 493856"
  },
  {
    "caption": "(D) Mutations in the CDGSH iron‐binding domain of NAF‐1 interfere with NAF‐1 binding to BCL‐2. H1299 HA‐BCL‐2b5 cells were infected with either Ad‐rtTA, Ad‐NAF‐1‐Flag, or Ad‐NAF‐1‐mut‐Flag (C99S C101S C110S H114Q). Lysates were treated as in (A). Densitometric analysis was performed using Scion Image software to quantify expression and co‐precipitated levels of NAF‐1‐Flag and NAF‐1‐mut‐Flag. Graph depicts the ratio of co‐precipitated protein to expression level.",
    "ncbi_link": "rtTA: 
BCL‐2: 596
NAF‐1: 493856"
  },
  {
    "caption": "(A) H1299 neo and HA‐BCL‐2b5 cells treated with control (CTRL) or NAF‐1 shRNA were either mock infected or infected with Ad‐BIK in the absence or presence of 50 μM zVAD‐fmk. Cell lysates were analysed by immunoblot.",
    "ncbi_link": "BCL‐2: 596
BIK: 638
NAF‐1: 493856"
  },
  {
    "caption": "(C) Prolonged BIK expression and caspase inhibition induces autophagy, which is enhanced by knockdown of NAF‐1. H1299 neo and HA‐BCL‐2b5 cells treated with CTRL or NAF‐1 shRNA were infected with Ad‐BIK in the presence of zVAD‐fmk for the indicated periods of time. Cell lysates were analysed by immunoblot. Levels of LC3 II were normalized to actin levels by densitometry analysis. Graph depicts normalized LC3 II levels of each lane.",
    "ncbi_link": "BCL‐2: 596
BIK: 638
NAF‐1: 493856"
  },
  {
    "caption": "(A) Effect of NAF‐1 knockdown on starvation‐induced autophagy. H1299 cells infected with CTRL or NAF‐1 shRNA were starved for 4 h in EBSS with DMSO (vehicle) or Baf A1 (100 nM). Cell lysates were analysed by immunoblot.",
    "ncbi_link": "NAF‐1: 493856"
  },
  {
    "caption": "(B) Representative images of GFP‐LC3 staining in H1299 GFP‐LC3 cells transfected with LUC or NAF‐1 siRNA, untreated and starved. Scale bar represents 10 μm.",
    "ncbi_link": "LUC: 
NAF‐1: 493856
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) Quantification of autophagy is expressed as the percentage of GFP‐LC3‐expressing cells displaying punctate GFP‐LC3. A minimum of 100 cells per sample were counted; results represent the average±s.d. of three independent experiments. Cell lysates were analysed by immunoblot.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) NAF‐1 contributes to the interaction between BCL‐2 and Beclin 1. H1299 HA‐BCL‐2b5 cells were transfected with Flag‐Beclin 1 and either LUC or NAF‐1 siRNA. Cells were lysed and subjected to immunoprecipitation with anti‐BCL‐2 antibody. Precipitates were subjected to analysis by immunoblot using anti‐Beclin 1 and anti‐BCL‐2. All lanes are derived from the same gel and of the same exposure. Thin white lines indicate where lanes have been removed.",
    "ncbi_link": "LUC: 
BCL‐2: 596
Beclin 1: 8678
NAF‐1: 493856"
  },
  {
    "caption": "(B) Loss of NAF‐1 prevents BCL‐2b5 from antagonizing starvation‐induced autophagy. H1299 GFP‐LC3 and BCL‐2b5/GFP‐LC3 cells were transfected with either LUC or NAF‐1 siRNA and starved for 4 h. Cells were analysed as in Figure 4C.",
    "ncbi_link": "LUC: 
BCL‐2: 596
NAF‐1: 493856
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) Representative electron micrographs of H1299 neo and HA‐BCL‐2b5 cells treated with either LUC or NAF‐1 siRNA, with or without subsequent starvation. Scale bar represents 10 μm. Cell lysates were analysed by immunoblot. All lanes are derived from the same gel and of the same exposure. Thin white line indicates where lanes have been removed. Autophagy levels observed by electron microscopy (C) were quantified and expressed as either the percentage of cells containing autophagic vacuoles (D) or the number of autophagosomes per cell (E). A minimum of 100 cells per sample were counted; results represent the average±s.e.m.",
    "ncbi_link": "LUC: 
BCL‐2: 596
NAF‐1: 493856"
  },
  {
    "caption": "(A) H1299 neo and HA‐BCL‐2b5 cells treated with either CTRL or NAF‐1 shRNA were loaded with Fura‐2AM, and ER Ca2+ stores were measured as the difference in cytoplasmic Ca2+ concentration before and after addition of TG (2 μM). Shown are representative traces of Fura‐2AM fluorescence measured at 340/380 nm excitation wavelength ratio at 510 nm wavelength emission. Arrow indicates time at which TG was added, delta values indicate TG‐sensitive ER Ca2+ stores.",
    "ncbi_link": "BCL‐2: 596
NAF‐1: 493856"
  },
  {
    "caption": "(C) Co‐immunoprecipitation of endogenous NAF‐1 and endogenous IP3 receptor type I. Lysate from H1299 HA‐BCL‐2b5 cells was collected and immunoprecipitation was performed with anti‐IP3R1 antibody. The resulting precipitate was analysed by immunoblot.",
    "ncbi_link": "BCL‐2: 596"
  },
  {
    "caption": "E) Representative images of prometaphase chromosomes from HeLa cells co-transfected with H2A.Z.2 siRNA and each of the constructs in D (green). Scale bar: 5μm. F) Quantification of the percentage of cells with micronuclei from experiment (E). The error bars represent the SD of three biological replicates (Control si N=887; H2A.Z.2 si N=1005; H2A.Z.2 si + wt N=760; H2A.Z.2 si + KR N=479). Data sets were statistically analysed using Chi-square test. ",
    "ncbi_link": "H2A.Z.2: 94239"
  },
  {
    "caption": "B) Representative images of metaphases from YFP:CENP-A (green) HeLa cells treated with Control (top) or H2A.Z.2 (bottom) siRNA. The white arrowheads indicate the mis-aligned chromosomes. Scale bar: 10 μm. C) Representative images of metaphase spreads from Control (top) or H2A.Z.2 (bottom) siRNA-transfected HeLa cells after FISH with a Chr17 centromeric probe (green). The arrowheads indicate the separated sister chromatids. Scale bar: 10 μm. ",
    "ncbi_link": "H2A.Z.2: 94239"
  },
  {
    "caption": "D) Representative images of HeLa cells transfected with Control (top) or H2A.Z.2 (bottom) siRNA, fixed, and stained for Sgo1 (green). Scale bar: 10 μm. E) Quantification of Sgo1 localisation in pro-metaphase cells from the experiment in (D). Error bar represents SD of two biological replicates. 35 pro-metaphase cells were analysed. ",
    "ncbi_link": "H2A.Z.2: 94239"
  },
  {
    "caption": "J) Representative images of HeLa YFP:CENP-A (green) mitotic cells after Control (top) or H2A.Z.2 (bottom) siRNA treatment. Scale bar: 5 μm. K) Violin plot of centromeric CENP-A intensity of pro-metaphase/metaphase cells from the experiments in J. (Control si N=197 H2A.Z.2 si N=260). The bar represents the median. Data sets were statistically analysed using the Wilcoxon rank test in R. **=p<0.01. L) Representative images of HeLa mitotic cells stained for CENP-C after Control (top) or H2A.Z.2 (bottom) siRNA treatment. Scale bar: 5 μm. M) Violin plot of centromeric CENP-C intensity of pro-metaphase/metaphase cells from the experiments in L. (Control si N=1083 H2A.Z.2 si N=686, from 3 biological replicas). The bars represent the median. Data sets were statistically analysed using the Wilcoxon rank test in R. ***=p<0.0001. ",
    "ncbi_link": "H2A.Z.2: 94239"
  },
  {
    "caption": "D) IGV analyses of H2A.Z localisation (from ENCODE) on Aurora B (green) and c-MYC (blue) genes showing H2A.Z enrichment at the TSS and at the upstream region respectively (bottom panels). IGV analyses of ATAC seq peaks for Control si and H2A.Z.1 si for Aurora B and MYC genes. The number in red represents the log2Ratio H2AZ.1 si/Control si.",
    "ncbi_link": "Aurora B: 9212
H2A.Z.1: 3015
H2AZ.1: 3015
c-MYC: 4609
MYC: 4609"
  },
  {
    "caption": "G) Representative images of HeLa cells transfected with control (top) or H2A.Z.1 (bottom) siRNA and stained for Lamin A/C (green). Scale bar = 10μm.",
    "ncbi_link": "H2A.Z.1: 3015"
  },
  {
    "caption": "D. Western blot analysis and quantification of phosphorylated PKD2 (S876) and phosphorylated PKD (S916/S876) in small intestine of Pkd2wt/wt and Pkd2ki/ki male mice. n=3.",
    "ncbi_link": "Pkd2: 18764"
  },
  {
    "caption": "A. Western blot and quantification of phosphorylated PKD (S916/S876) in small intestine of Pkd2flox/flox and Pkd2gutΔ/Δ male mice. n=3. B. Western blot and quantification of phosphorylated PKD (S744-748) in small intestine of Pkd2flox/flox and Pkd2gutΔ/Δ male mice. n=3. C ",
    "ncbi_link": "Pkd2: 18764"
  },
  {
    "caption": "A. Western blot (WB) analysis of specified proteins in small intestine of Pkd2wt/wt and Pkd2ki/ki male mice after one week of HFD. Quantification of the bands for each protein normalized to loading control and relative to Pkd2wt/wt. n=3.",
    "ncbi_link": "Pkd2: 18764"
  },
  {
    "caption": "F. Quantification of Oct4, Nanog and Rex1 expression in trisomic and wild-type ES cell derived EBs at day 8 of differentiation. Error bars, ±S.D. n=3. ** P < 0.01.",
    "ncbi_link": "Nanog: 71950
Oct4: 18999
Rex1: 22702"
  },
  {
    "caption": "B. Quantification of Nanog expression in trisomic, wild-type, and mixed ES cell-derived EBs cultured for 8 days. Error bars, ±S.D. n=3. ** P < 0.01.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "I, J. Cumulative cell numbers of WT and Tfcp2l1_KO 2i-ESCs (I) and FBS-ESCs (J). Results are from three independent clones of WT and Tfcp2l1_KO ESCs.",
    "ncbi_link": "Tfcp2l1: 81879"
  },
  {
    "caption": "A. Real-time fatty acid oxidation (FAO) profile of WT and Tfcp2l1_KO  2i-ESCs using the FAO stress test kit in Seahorse XF. Oxygen consumption rate  (OCR) were measured. Error bars indicate SEM; n = 5 biological repeats.  Palm-BSA, palmitate conjugated BSA, a substrate of FAO; Oligomycin, an inhibitor of ATP synthase (complex V); FCCP,  Carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, a proton gradient uncoupler; Rotenone and Antimycin, a complex I inhibitor and a complex III inhibitor, respectively.",
    "ncbi_link": "Tfcp2l1: 81879"
  },
  {
    "caption": "G. Percentage of dead cells measured by live-cell propidium iodide staining detecting spontaneous cell death in 2i-ESCs. n=3 biological repeats; error bars indicate SEM; p-values were calculated using two-sample t-test. H. Cumulative cell number of WT, Tfcp2l1_KO, and Tfcp2l1_KO with Cpt1a overexpression (OE)  2i-ESCs. Error bars indicate SEM; n=3 biological repeats; p-values were calculated using two-sample t-test. ",
    "ncbi_link": "Cpt1a: 12894
Tfcp2l1: 81879"
  },
  {
    "caption": "D. Live-cell propidium iodide staining to measure cell death in WT, Tfcp2l1_KO, and Tfcp2l1_KO with Cpt1a overexpression (OE) 2i-ESCs after 5 mM 2-DG treatment for 24 hours. n=3 biological repeats; error bars indicate SEM; p-value were calculated using two-sample t-test.",
    "ncbi_link": "Cpt1a: 12894
Tfcp2l1: 81879"
  },
  {
    "caption": "E. Immunoblotting of WT and  Tfcp2l1_KO 2i-ESCs untreated or treated with 200 nM INK-128.",
    "ncbi_link": "Tfcp2l1: 81879"
  },
  {
    "caption": "F.  Real-time PCR showing Cpt1a mRNA levels in WT and  Tfcp2l1_KO 2i-ESCs in the presence and absence of 200 nM INK-128. n=3 biological repeats; error bars indicate SEM; p-values were calculated using two-sample t-test.",
    "ncbi_link": "Cpt1a: 12894
Tfcp2l1: 81879"
  },
  {
    "caption": "Immunofluorescence images of U2OS expressing wild-type or ∆LIR mutant FLAG-HA-FAM134 proteins after 24hrs doxycycline induction under different conditions (basal=DMSO, Baf.A1=2h 200nM Bafilomycin A1, EBSS=2h starvation in EBSS) Scale bar: 10μm; staining against FAM134 (HA; green) and endogenous LC3B (red).",
    "ncbi_link": "FLAG: 
HA: 
FAM134: 79137"
  },
  {
    "caption": "Western blot for Fam134 proteins in indicated MEFs, expressing the ER-phagy reporter ssRFP-GFP-KDEL and being reconstituted with the respective wild-type or ∆LIR mutant Fam134 protein.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Profile plots showing the Log2 LFQ intensity (G) and representative immunofluorescence (H) of Climp63 (green) in wild-type and Fam134 knockout MEFs.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Profile plots showing the Log2 LFQ intensity (I) and representative immunofluorescence (J) for collagen I (red) expression in wild-type and Fam134 knockout MEFs. Scale bar: 10μm. Inset scale bar: 5μm. Nuclei were stained with Hoechst 33342.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Electron microscopy of wild-type and Fam134 single knockout MEFs (ER=endoplasmic reticulum). Scale bar: 500nm.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Immunofluorescence images stained for endogenous Calnexin (Canx) or Climp63 in wild-type (WT), Fam134 knockout MEFs, and Fam134 knockout MEFs reconstituted with the respective wild-type or ∆LIR mutant Fam134 protein. Scale bar: 10μm. Inset scale bar: 5μm.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Representative Western Blot of Collagen I in wild-type MEFs and Fam134 knockout MEFs reconstituted for the respective wild-type (WT) or ∆LIR mutant Fam134 protein. Vinculin has been used as reference for ratio calculation. The statistical significance was estimated by unpaired Student's t test. All data are represented as mean ± s.e.m. of n=3 biological experiments and the statistical significance is defined as * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Fam134: 227298"
  },
  {
    "caption": "Representative Western Blot (D) and the relative bar plot (E) showing collagen expression in Fam134b knockout MEFs overexpressing wild type and the ∆LIR Fam134a protein.",
    "ncbi_link": "Fam134b: 66270
Fam134a: 227298"
  },
  {
    "caption": "Representative Western Blot (F) and the relative bar plot (G) showing collagen expression in Fam134b knockout MEFs overexpressing wild type Fam134a and Fam134c. Representative Western Blot (H) and the relative bar plot (I) showing collagen expression in Fam134c knockout MEFs overexpressing wild type Fam134a and Fam134b.",
    "ncbi_link": "Fam134b: 66270
Fam134a: 227298
Fam134c: 67998"
  },
  {
    "caption": "Representative Western Blot (J) and the relative bar plot (K) showing collagen expression in Fam134a knockout MEFs overexpressing wild type Fam134b. Representative Western Blot (L) and the relative bar plot (M) showing collagen expression in Fam134a knockout MEFs overexpressing wild type Fam134c.",
    "ncbi_link": "Fam134b: 66270
Fam134a: 227298
Fam134c: 67998"
  },
  {
    "caption": "A, B UMAP plots of Dataset 3 which contains five WT (DN3a, DN3b γδ+, DN4 γδ+, DN3b γδ- and DN4 γδ-) and two Lat-/- (DN3 γδ- and DN3 γδint) scRNAseq datasets. The UMAP plot is colored according to sorted samples (A), and to expression levels of the specified genes (B).",
    "ncbi_link": "Lat: 16797"
  },
  {
    "caption": "A-C qRT-PCR detection of mRNA levels of  IL-1β, TNFα and IL-6 mRNA levels in  CCDC50-WT and CCDC50-KO THP-1 cells primed with LPS and then treated with ATP and Nigericin (A), or infected with Listeria monocytogenes at a multiplicity of infection (MOI) of 10 and Salmonella typhimurium (MOI of 10) for 6 h (B) or MSU (40 μg/ml ) and SiO2  (40 μg/ml) for 6 h (C) (n = 3 biological replicates). Data information: L.m, Listeria monocytogene; S.t, Salmonella typhimurium; MSU, Monosodium urate; mRNA results are normalized to GAPDH  and relative to untreated wild-type cells Data are representative of three biological replicates and shown as mean with SEM (A-C); **P < 0.01, ***P < 0.001; two-tailed unpaired Student's t-test.",
    "ncbi_link": "CCDC50: 152137
GAPDH: 2597
IL-1β: 3553
IL-6: 3569
TNFα: 7124"
  },
  {
    "caption": "E-G  CCDC50-WT and  CCDC50-KO  THP-1 cells were stimulated as in (A-C). The cells were collected for immunoblot analysis of pro-caspase-1, and the supernatants were subjected to cleaved  caspase-1 and  IL-1β analysis. The expression levels of cleaved-caspase-1 and cleaved-IL-1β were quantitated using ImageJ software. Data information: L.m, Listeria monocytogene; S.t,  Salmonella typhimurium; MSU, Monosodium urate; Casp1,  caspase-1; actin  was used as a loading control.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "C qRT-PCR detection of Il6, IL-1β and Tnfα mRNA levels in Ccdc50+/+ and Ccdc50-/- BMDMs primed with LPS for 3 h and then induced with ATP and Nigericin (A),  L.m and  S.t (B), or MSU  and  SiO2 (C) for indicated time points (n = 3 biological replicates). D-F Ccdc50+/+ and  Ccdc50-/- BMDCs treated as BMDMs  were collected and subjected to qRT-PCR analysis (n = 3 biological replicates). Data information: mRNA data are normalized to GAPDH  and relative to untreated wild-type cells; Data are representative of three biological replicates and are shown as the mean with SEM *P <0.05, **P < 0.01, ***P < 0.001; two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ccdc50: 67501
GAPDH: 14433
IL-1β: 16176
Il6: 16193
Tnfα: 21926"
  },
  {
    "caption": "G ELISA  analysis of the protein level of secreted  IL-1β in supernatants of Ccdc50+/+ and Ccdc50-/- BMDMs  (top panel) and BMDCs  (bottom panel) treated as in (A-C) (n = 3 biological replicates). Data information: Data are representative of three biological replicates and are shown as the mean with SEM *P <0.05, **P < 0.01, ***P < 0.001; two-tailed unpaired Student's t-test.",
    "ncbi_link": "Ccdc50: 67501"
  },
  {
    "caption": "H,I Ccdc50+/+ and  Ccdc50-/- BMDMs (H) and  BMDCs (I) were treated as in (A-C). The cells were lysed for western blotting analysis of  pro-caspase-1  and the supernatant was collected for  immunoblots of cleaved-caspase-1. The expression levels of cleaved-caspase-1 were quantitated using ImageJ software.",
    "ncbi_link": "Ccdc50: 67501"
  },
  {
    "caption": "F Immunoblot analysis of lysates from HEK293  cells cotransfected with Flag- AIM2, -NLRP3, -ASC and  HA-CCDC50 or empty control vector. The expression  levels of Flag-tagged proteins and Actin were quantitated using ImageJ software. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "Flag: 
HA: 
AIM2: 9447
CCDC50: 152137
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "G  Immunoblot analysis of  HEK293 cells transfected with FLAG-NLRP3 and an increasing amount of  HA-CCDC50 plasmids. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "FLAG: 
HA: 
CCDC50: 152137
NLRP3: 114548"
  },
  {
    "caption": "H Immunoblot  analysis of lysates from CCDC50-KO and CCDC50-WT  THP-1  cells induced with  LPS  plus  ATP and then treated with cycloheximide (CHX) for indicated  time points. The expression  levels of NLRP3 and  Actin were quantitated using ImageJ software. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "I  HEK293  cells were co-transfected with Flag-NLRP3 and HA-CCDC50 or empty control vector for 24 h and then treated with MG132, NH4Cl, 3-MA, CQ or DMSO  for another 6 h. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "Flag: 
HA: 
CCDC50: 152137
NLRP3: 114548"
  },
  {
    "caption": "J Immunoblot analysis of NLRP3 in CCDC50-WT and CCDC50-KO THP-1 cells stimulated with LPS  in combination with  ATP. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "K Western blotting analysis of ATG5 wild-type or knockout  HEK293T cells co-transfected with Flag-NLRP3 and  HA-CCDC50  or empty control vector for 24 h. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "Flag: 
HA: 
ATG5: 9474
CCDC50: 152137
NLRP3: 114548"
  },
  {
    "caption": "L Immunoblot  analyses of NLRP3 in HEK293  cells in the presence of CCDC50  or its mutant  CCDC50 with the deletion of MIUs. Data information: actin was used as a loading control. All the experiments were repeated at least once.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "A Denature-IP (with anti-Flag) and immunoblot analysis of polyubiquitinated NLRP3 in HEK293  cells transfected with Flag-NLRP3, HA-Ub (ubiquitin) as well as HA- CCDC50 or empty vector for 24 h.",
    "ncbi_link": "Flag: 
HA: 
CCDC50: 152137
NLRP3: 114548"
  },
  {
    "caption": "F The colocalization  analysis of NLRP3 and LC3B  in CCDC50-WT and CCDC50- KO  HeLa cells stimulated with LPS plus ATP; scale bars, 5 μM. Data information: The nuclei were  stained with DAPI; data are representative of three individual experiments.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "G The  oligomerization analysis  of  NLRP3 in CCDC50 wild-type and knockout THP-1  cells stimulated with  LPS as well as ATP. LPS-primed (1 μg/ml, 3 h)  THP-1 cells were stimulated with  ATP (5 mM) for another 30 min and then were collected and lysed. The cell lysates were centrifuged and separated into soluble  and insoluble fractions. The soluble fraction was analyzed by SDS-PAGE. The insoluble fraction was analyzed by  native-PAGE.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "H The  oligomerization analysis  of NLRP3 in HEK293  cells transfected with plasmids expressing Flag-NLRP3, HA-CCDC50  or empty vector for 24 h, and then treated with  DMSO or CQ for 6 h. After treatment, the cells were collected and lysed. The cell lysates were centrifuged and separated into soluble and insoluble fractions. The soluble fraction was analyzed by SDS-PAGE. The  insoluble fraction was analyzed by  native-PAGE.",
    "ncbi_link": "Flag: 
HA: 
CCDC50: 152137
NLRP3: 114548"
  },
  {
    "caption": "J Confocal microscopy analysis of colocalization  between NLRP3  and ASC  in CCDC50-WT and CCDC50-KO HeLa cells stimulated with LPS plus  ATP; scale bars, 5 μM. Data information: The  nuclei  were stained  with DAPI; data are representative of three individual experiments.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "K Confocal microscopy  analysis of ASC speck formation in CCDC50-WT and CCDC50-KO HeLa cells stimulated with LPS plus ATP; scale bars, 5 μM. Data information: The nuclei  were stained with DAPI; data are representative of three individual experiments.",
    "ncbi_link": "CCDC50: 152137"
  },
  {
    "caption": "(E) CSF1R, MRC1, TLR2 and FOS relative expression measured by qRT-PCR for LGCs (upper), FBGCs (middle) and osteoclasts (lower), following the cell membrane fusion regulator DC-STAMP knockdown. si-Ctrl, scrambled siRNA; si-DC-STAMP, DC-STAMP siRNA; n=7 donors.",
    "ncbi_link": "CSF1R: 1436
DC-STAMP: 81501
FOS: 2353
MRC1: 4360
TLR2: 7097"
  },
  {
    "caption": "(A) Real-time quantitative PCR (RT-qPCR) of transcripts changing differentially between compartments using the compartmentalized cultures after 48 hours PTX-treatment. n=8 independent biological replicates (except for Plk2 (n=7), where one measurement couldn't be performed due to insufficient cDNA); PTX-effect was assessed by three-way ANOVA followed by Tukey's post-hoc multiple comparison test; *p < 0.05; **p < 0.01.",
    "ncbi_link": "Plk2: 83722"
  },
  {
    "caption": "(B) Representative images of single-molecule FISH (smFISH) in either control or 48 h PTX-treated rat hippocampal neurons (DIV20) using probes specific for Add2, Dnajc6 and Sort1 (green). MAP2 immunostaining (red) was used to visualize neuronal somata and dendrites. Inserts at higher magnification illustrate PTX-dependent changes in dendritic RNA puncta. Scale bar = 10 μm. (C) Quantification of B. (n=3-4 independet biological replicates with 8-10 cells averaged per condition and replicate; two-sample Student's t-test; *p < 0.05; **p < 0.01). B",
    "ncbi_link": "Add2: 24171
Dnajc6: 313409
Sort1: 83576"
  },
  {
    "caption": "A, B, Western blotting analysis of proteins co-precipitated with anti-FLAG antibody from testis extracts of E15.5 wild-type embryos and transgenic embryos expressing FLAG-tagged NANOS2 with or without RNase (A) or from extracts of HeLa cells transfected with FLAG-tagged DND1 and with or without HA-tagged NANOS2 (B).",
    "ncbi_link": "DND1: 373863
NANOS2: 378430
NANOS2: 339345"
  },
  {
    "caption": "Precipitates were analyzed with the indicated antibodies. C, GST pull-down assay using E. coli extracts expressing GST, GST-fused NANOS2, or NANOS3 mixed with MBP-tagged LacZ or DND1. Precipitates were analyzed by Coomassie Brilliant Blue (CBB) staining or western blotting with an anti-MBP antibody. An arrowhead indicates MBP-DND1 co-precipitated with GST-tagged NANOS2 or NANOS3.",
    "ncbi_link": "LacZ: 
DND1: 373863
NANOS2: 339345
NANOS3: 342977"
  },
  {
    "caption": "D, E, Western blotting analyses of proteins co-precipitated with anti-FLAG antibody from extracts of HeLa cells transfected with FLAG-tagged NANOS2, NANOS2 (ΔN10), NANOS2 (ΔC10), NANOS2 (C61A, C96A) or NANOS3, and HA-tagged DND1 (D)",
    "ncbi_link": "DND1: 373863
NANOS2: 339345
NANOS3: 342977"
  },
  {
    "caption": "D, E, Western blotting analyses of proteins co-precipitated with anti-FLAG antibody from extracts of HeLa cells transfected with FLAG-tagged NANOS2, NANOS2 (ΔN10), NANOS2 (ΔC10), NANOS2 (C61A, C96A) or NANOS3, and HA-tagged DND1 (D) or with FLAG-tagged NANOS2, NANOS2 (C61A), NANOS2 (C96A) or NANOS2 (C61A, C96A), and HA-tagged DND1 (E).",
    "ncbi_link": "DND1: 373863
NANOS2: 339345"
  },
  {
    "caption": "Precipitates were analyzed with the indicated antibodies. F, GST pull-down assay using E. coli extracts expressing GST-fused DND1 mixed with MBP-tagged LacZ, NANOS2, NANOS2 (C61A, C96A) or NANOS2 (60-114). Arrowheads indicate MBP-tagged NANOS2 (lane 2) or NANOS2 (60-114) (lane 4).",
    "ncbi_link": "LacZ: 
DND1: 373863
NANOS2: 339345"
  },
  {
    "caption": "Western blotting analyses of proteins co-precipitated with anti-FLAG antibody from extracts of HeLa cells transfected with HA-tagged NANOS1, NANOS2 or NANOS3, and FLAG-tagged DND1 (A)",
    "ncbi_link": "DND1: 373863
NANOS1: 340719
NANOS2: 339345
NANOS3: 342977"
  },
  {
    "caption": "Western blotting analyses of proteins co-precipitated with anti-FLAG antibody from extracts of HeLa cells transfected with HA-tagged NANOS1, NANOS2 or NANOS3, and FLAG-tagged DND1 (A) or with FLAG-tagged PUMILIO1 or PUMILIO2, and HA-tagged NANOS1, NANOS2 or NANOS3 with or without MYC-tagged DND1 (B).",
    "ncbi_link": "DND1: 373863
NANOS1: 340719
NANOS2: 339345
NANOS3: 342977
PUMILIO1: 9698
PUMILIO2: 23369"
  },
  {
    "caption": "C, Characterization of antibodies against PUMILIO1 and PUMILIO2. Western blotting analyses of Flag-tagged PUMILIO1 and PUMILIO2 in HeLa cells transfected with FLAG-tagged PUMILIO1 or PUMILIO2 using antibodies against FLAG, PUMILIO1 or PUMILIO2. Note that the antibodies against PUMILIO1 specifically recognized FLAG-tagged PUMILIO1 while the anti-PUMILIO2 antibody could detect both Flag-tagged PUMILIO1 and PUMILIO2 but less actively.",
    "ncbi_link": "PUMILIO1: 9698
PUMILIO2: 23369"
  },
  {
    "caption": "D, FLAG-tagged NANOS2 was immunoprecipitated with an anti-FLAG antibody from E15.5 testicular extracts from transgenic mice expressing FLAG-tagged NANOS2. Precipitates were analyzed by western blotting with the indicated antibodies. Note that co-precipitation of both PUMILIO1 and PUMILIO2 were not detected even though both CNOT1 and DND1 were clearly co-precipitated.",
    "ncbi_link": "NANOS2: 378430"
  },
  {
    "caption": "Figure 3 | DND1 co-localizes with NANOS2 in P-bodies. A−C, Sections of male gonads from E15.5embryos were immunostained with antibodies against DND1 (green) and DCP1a (red). D−F, Squash preparation of a male gonocyte from E16.5embryoimmunostained with antibodies against DND1 (red) and DCP1a (green). Arrowheads indicate co-localization of DND1 and DCP1a. G−I, Sections of male gonads from E15.5embryos were immunostained with antibodies against DND1 (red) and NANOS2 (green). Arrowheads indicate co-localization of DND1 and NANOS2. J−M, NIH3T3 cells transfected with HA-tagged Dnd1 and FLAG-tagged Nanos2 were then immunostained with antibodies against DND1 (J) (magenta), NANOS2 (K) (red), and DCP1a (L) (green). N−Y, Biomolecular fluorescence complementation assay. NIH3T3 cells transfected with VENUS-C-fused Dnd1 and VENUS-N-fused Nanos2 (N−U) or Nanos2 (C61A, C96A) (V-γ) were immunostained with antibodies against DND1 (N, S, V), NANOS2 (O, W, α) or DDX6 (R, Z). Then, the signals of VENUS fusion protein were visualized (P, T, X, β). Arrowheads in Z indicate P-bodies. DNA was labeled with DAPI (blue). Scale bars: 50 m in A for A−C; 10 m in D for D-F, G for G−I, J for J−M, N for N−γ. Insets in A-C and J-γ show an enlarged vision of each picture to better depict localization of each protein. See also Fig. EV2T-Y.",
    "ncbi_link": "Dnd1: 213236
Nanos2: 378430"
  },
  {
    "caption": "A, Western blotting analyses of proteins in testes from E13.5 to E16.5 embryos of Dnd1flox/flox or Dnd1flox/flox_Tg(Oct4PE-CreERT2) each administered with tamoxifen at E13.5 and E15.5 embryos of Nanos2+/- or Nanos2-/- with the indicated antibodies.",
    "ncbi_link": "CreERT2: 
Oct4PE: 
Dnd1: 213236
Nanos2: 378430"
  },
  {
    "caption": "B-P, Sections of testes from Dnd1flox/flox (B, E, H, K, N), Dnd1flox/flox_Tg(Oct4PE-CreERT2) (C, F, I, L, O) or Nanos2-/- (D, G, J, M, P) embryos were prepared at E16.5 and then immunostained with antibodies against pH3 (B-D), STRA8 (E-G), SYCP3 (H-J), activated-Caspase3 (K-M) or LAMININ (N-P) (green). Germ cells were immunostained with TRA98 (B-D) or DAZL (N-P) (red), and DNA was labeled with DAPI (blue). Tamoxifen was administered at E13.5. Scale bars: 50 m in B for B−D and K-P, 50 m in E for E−J. See also Fig. EV3.",
    "ncbi_link": "Dnd1: 213236
Nanos2: 378430"
  },
  {
    "caption": "A-L, Sections of testes from Dnd1flox/flox (A, B, C, G, H, I, M, N, O) and Dnd1flox/flox_Tg(Oct4PE-CreERT2) (D, E, F, J, K, L, P, Q, R) embryos were prepared at E16.5 and then immunostained with antibodies against NANOS2 (A, D) (green), DCP1a (G, J) (green), DDX6 (M, P) (green) and TRA98 (B, E, H, K, N, Q). DNA was labeled with DAPI (blue). Tamoxifen was administered at E13.5. Scale bars: 50 m in A for A−F; 50 m in G for G-L; 50 m in M for M-R. Insets show an enlarged vision of each picture to better depict localization of NANOS2, DCP1a and DDX6.",
    "ncbi_link": "Oct4PE: 
CreERT2: 
Dnd1: 213236"
  },
  {
    "caption": "S-V, Immunoprecipitation with an anti-FLAG antibody from E15.5 male gonadal extracts of wild-type and the transgenic mouse line expressing FLAG-tagged DND1 (S, T), or with an anti-NANOS2 antibody from E15.5 male gonadal extracts of Dnd1flox/flox mice with or without Oct4PE-CreERT2 (U, V). Precipitates were analyzed by western blotting (S, U) or by RT-qPCR (T, V). The RT-qPCR data are shown as average relative mRNA levels ± SEs (n=3).",
    "ncbi_link": "Oct4PE: 
CreERT2: 
DND1: 213236
Dnd1: 213236"
  },
  {
    "caption": "W, X, Western blotting analyses of proteins in NANOS2-depleted (W) or DND1-depleted (X) testis extracts from E15.5 embryos. Proteins were analyzed with the indicated antibodies.",
    "ncbi_link": "DND1: 213236
NANOS2: 378430"
  },
  {
    "caption": "C Comparison of meiotic chromosome segregation in cells lacking H3K9me3 depending on Swi6's affinity towards H3K9me2. Exemplary IF microscopy images of the indicated fission yeast strains are shown. Homothallic strains were incubated on SPAS plates. DNA and tubulin were stained with DAPI and anti-TAT-1, respectively. Missegregating chromosome is indicated with a yellow arrow; D Quantification of meiotic chromosome segregation phenotypes. The data for clr4+ and clr4F449Y is the same as in Fig 3B. P values were calculated using Fisher's exact test. Number of total cells counted is indicated in each bar.",
    "ncbi_link": "clr4: 2540825
Swi6: 2541633"
  },
  {
    "caption": "E Comparison of co-segregation of centromere I (CenI) during MI in cells lacking H3K9me3 depending on Swi6's affinity towards H3K9me2. Exemplary live cell microscopy images of the indicated fission yeast strains during MI and MII are shown. Heterothallic strains were crossed and dyads as well as tetrads were subjected to the analysis. Heterozygous CenI-GFP was used to follow the segregation pattern during meiosis. The GFP-signal is additionally displayed in greyscale for better visibility F Quantification of CenI-GFP segregation during meiosis. The data for clr4+ and clr4F449Y is the same as in Fig 3D. P values were calculated using Fisher's exact test. Number of total cells counted is indicated in each bar.",
    "ncbi_link": "clr4: 2540825
Swi6: 2541633"
  },
  {
    "caption": "G Tetrad dissection to asses spore viability in clr4F449Y swi6Chp1-like-CD cells. Exemplary image (left) and quantification of the spore viability (right) are shown. Meiosis was induced in homothallic cells and the resulting spores were dissected. The data for clr4+ and clr4F449Y is the same as in Fig 3F. P values were calculated using Fisher's exact test. Number of dissected tetrads is indicated in each bar.",
    "ncbi_link": "clr4: 2540825
swi6: 2541633"
  },
  {
    "caption": "B. Violin plots depicting the distribution of the quantified average cellular expression of Prok2, ProkR2, Vip, Vipr2, Avp, Avpr1a, Grp and Grpr in each sub-cluster in CT7.5 (left) and CT15.5 (right) datasets.",
    "ncbi_link": "Avp: 11998
Avpr1a: 54140
Grp: 225642
Grpr: 14829
Prok2: 50501
ProkR2: 246313
Vip: 22353
Vipr2: 22355"
  },
  {
    "caption": " C. The period of Cry1-luc bioluminescence rhythms in SCN slices transfected with either pProk2.Cre.T2A.mCherry or pProkR2.Cre.T2A.Venus does not differ between treatments (p=0.71, n= 10, 9 SCN slices per group, respectively). D. Similarly, the amplitude of Cry1-luc bioluminescence rhythms from Prok2+ SCN cells and ProkR2+ SCN cells, does not differ between treatments (p=0.67). ",
    "ncbi_link": "luc: 
mCherry: 
Venus: 
Cre: 2777477
Cry1: 12952
Prok2: 50501
ProkR2: 246313"
  },
  {
    "caption": " H. Left: confocal images of representative SCN slices dual-transfected with pProk2.Cre.T2A.mCherry and Syn.GCaMP6f (top), or pProkR2.Cre.T2A.Venus and Syn.jRCaMP1a (below) (scale bar=500µm). Right, above: representative detrended plots of signal from GCaMP6f (green) traces and pCry1-DIO-Luc, emitted from Prok2+ SCN cells (red). Right, below: representative detrended plots of jRCaMP1a (purple) and pCry1-DIO-Luc emitted from ProkR2+ cells (light green). Orientation bars depict the horizontal axis of the optic chiasm and the vertical axis of the third ventricle for each SCN. ",
    "ncbi_link": "GCaMP6f: 
jRCaMP1a: 
Luc: 
mCherry: 
Venus: 
Cre: 2777477
Cry1: 12952
Prok2: 50501
ProkR2: 246313
Syn: 20964"
  },
  {
    "caption": " B. Comparison of the Per2::Luciferase rhythm amplitude of the cycle preceding and the first and second cycles succeeding vehicle (applied CT23-20 dark grey n=12 SCN slices, CT-20-23 light grey n=6 SCN slices) or Prok2RA (applied CT23-20 purple n=13 SCN slices, CT20-23 pink n=11 SCN slices) treatment (interaction, p<0.0001). A significant decline in amplitude occurred when Prok2RA signalling was blocked between CT20-23 (****p<0.0001). ",
    "ncbi_link": "Luciferase: 
Per2: 18627"
  },
  {
    "caption": "  H. Period lengthening occurred at the same rate when Prok2.Cre or ProkR2.Cre was the first AAV to be applied (p=0.1; Prok2.Cre - baseline vs. 1 AAV, *p=0.01; baseline vs. both AAVs, *p=0.04; ProkR2.Cre - baseline vs. 1 AAV, *p=0.03; baseline vs. both AAVs, **p=0.01. ",
    "ncbi_link": "Cre: 2777477
Prok2: 50501
ProkR2: 246313"
  },
  {
    "caption": " A. Representative Per2::Luciferase traces of Cry1,2-/- SCN slices at baseline (black, arrhythmic), after Cry1 complementation in Prok2+ cells (red) and further complementation in ProkR2+ cells (yellow, rhythmic) (cohort n=8). B. as in A but order of complementation reversed (green =Cry1 complementation in ProkR2+ cells) (cohort n=8). ",
    "ncbi_link": "Luciferase: 
Cry1: 12952
Per2: 18627"
  },
  {
    "caption": "AR-dependent luciferase assays were performed on LNCaP  cells transfected with siTRIM33 or negative control (NC) (A), increasing amounts of TRIM33  plasmid (B)  Western blot analysis shows the protein level of TRIM33  in LNCaP  cells after TRIM33  knockdown (A) or overexpression (B). Data information: , data are presented as mean ± SD (n = 3 independent experiments). *P < 0.05; **P < 0.01; ns=not significant (two-way ANOVA).",
    "ncbi_link": "TRIM33: 51592"
  },
  {
    "caption": "A-D, AR  transcript levels were measured by  RT-qPCR on LNCaP  cells (A and C) or VCaP  cells (B and D) transfected with siTRIM33  or the TRIM33  expression construct and treated with EtOH  or DHT. Protein lysates were harvested at 72 h after transfection and subjected to western blot  analysis with the indicated antibodies. Data information: In (A-D, data are presented as mean ± SD (n = 3 independent experiments). * P < 0.05, **P < 0.01, ns=not significant (two-way ANOVA).",
    "ncbi_link": "AR: 367
TRIM33: 51592"
  },
  {
    "caption": "E and F, LNCaP  cells transfected with siTRIM33 or NC were treated with cycloheximide  (CHX). Protein lysates were harvested at the indicated time points for  western blot analysis. AR  protein levels were quantified and normalized to β-actin and then plotted relative to 0 h. Data information: In F, data are presented as mean ± SD (n = 3 independent experiments). * P < 0.05, **P < 0.01, ns=not significant (two-way ANOVA).",
    "ncbi_link": "TRIM33: 51592"
  },
  {
    "caption": "G, LNCaP  cells transfected with siTRIM33  or NC were treated with DMSO  or MG132  for 8 h. Protein lysates were extracted and subjected to western blot analysis with the indicated antibodies.",
    "ncbi_link": "TRIM33: 51592"
  },
  {
    "caption": "HA-Ub   was expressed in LNCaP  cells co-transfected with siTRIM33 (H) The cells were treated with MG132  for 4 h before harvesting. Endogenous AR  was immunoprecipitated  from cell lysates, and interacting  proteins were detected by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "HA: 
TRIM33: 51592
Ub: 7311///7316///7314///6233"
  },
  {
    "caption": "I, HA-Ub  was expressed in LNCaP  cells co-transfected with the TRIM33  expression construct (I). The cells were treated with MG132  for 4 h before harvesting. Endogenous AR  was immunoprecipitated  from cell lysates, and interacting  proteins were detected by immunoblotting  with the indicated antibodies.",
    "ncbi_link": "HA: 
TRIM33: 51592
Ub: 7311///7316///7314///6233"
  },
  {
    "caption": "LNCaP  cells transiently expressing myc-tagged Skp2  with Flag-TRIM33  were harvested and subject to immunoblot  analysis with the indicated antibodies.",
    "ncbi_link": "Flag: 
myc: 
Skp2: 6502
TRIM33: 51592"
  },
  {
    "caption": "K, LNCaP  cells transiently expressing myc-tagged SPOP  with Flag-TRIM33  were harvested and subject to immunoblot analysis with the indicated antibodies.",
    "ncbi_link": "Flag: 
myc: 
SPOP: 8405
TRIM33: 51592"
  },
  {
    "caption": "L, shTRIM33- or shCtrl-LNCaP  cell lines transfected with NC or siSkp2 were harvested 72 h after transfection and subjected to immunoblot  analysis with the indicated antibodies.",
    "ncbi_link": "Skp2: 6502
TRIM33: 51592"
  },
  {
    "caption": "M, HEK293T  cells were co-transfected with flag-TRIM33   and various myc-tagged AR  constructs.  AR-FL and AR truncated mutants were immunoprecipitated  with an anti-myc  antibody and then subjected to western blot analysis with the indicated antibodies.",
    "ncbi_link": "myc: 
AR: 367"
  },
  {
    "caption": "N, HEK293T   cells were co-transfected with myc-AR-N and various flag-tagged TRIM33  constructs. AR-N was immunoprecipitated with an anti-myc  antibody and then subjected to western blot  analysis with the indicated antibodies.",
    "ncbi_link": "flag: 
myc: 
AR: 367
TRIM33: 51592"
  },
  {
    "caption": "O, LNCaP  cells were transfected with various flag-tagged TRIM33  constructs. AR-associated proteins were immunoprecipitated  with an anti-AR  antibody and then subjected to western blot  analysis with the indicated antibodies.",
    "ncbi_link": "flag: 
TRIM33: 51592"
  },
  {
    "caption": "P, LNCaP  cells were co-transfected with myc-Skp2  and various flag-TRIM33  constructs. AR  and other proteins were detected by western blot  analysis with the indicated antibodies.",
    "ncbi_link": "flag: 
myc: 
Skp2: 6502
TRIM33: 51592"
  },
  {
    "caption": "Q, AR pull-down was performed on protein extracts from MG132-treated HEK293T  cells overexpressing myc-AR, HA-Ub, myc-Skp2, and various flag-tagged TRIM33  constructs. AR ubiquitination  and specific protein levels were detected by  western blot  analysis with the indicated antibodies.",
    "ncbi_link": "flag: 
HA: 
myc: 
AR: 367
Skp2: 6502
TRIM33: 51592
Ub: 7311///7316///7314///6233"
  },
  {
    "caption": "A, TRIM33  mRNA expression  levels were analyzed in normal and tumor samples from multiple publicly available patient  cohorts. A two-sided Wilcoxon signed-rank test was used for the TCGA Prostate, Ding 2016, and Jing 2020 datasets, while a two-sided Wilcoxon rank-sum test was used for the other datasets. Measurements shown in box plots are the first and third quartiles and are split by the medians, whiskers extending a 1.5-fold interquartile range beyond the box.",
    "ncbi_link": "TRIM33: 51592"
  },
  {
    "caption": "(C) Confocal z-stack images showing the presence of ARSA-positive cells (green) co-stained with oligodendrocyte markers CNPase and APC (arrows). (D) Undetectable ARSA immunoreactivity in tissues of untreated animals. In all pictures nuclei are counterstained with ToPro (blue). Scale bars: A, 80 µm; B, D 60µm, C, 80µm",
    "ncbi_link": "ARSA: 410"
  },
  {
    "caption": "Vector copy number (VCN) cartography shows integrated LV genome (assessed by qPCR) along the rostro-caudal axis (slices 1-10) in LV.hARSA-injected S1.1 and S2.2 NHP in a side-by-side comparison with ARSA mRNA expression (assessed by qPCR analyses using probe and primers annealing to sequences conserved in both the human and Macaca fascicularis and expressed as fold increase to region-matched blocks of the contralateral hemisphere). Grading of colors for VCN ranged from white (VCN<0.001; corresponding to CT>37) to dark orange (VCN=1-3). The highest VCN is found in close correspondence to the injection sites, as confirmed by comparison with post-surgery MR images (yellow and orange circles indicate viral suspension close to the injection sites). Grading of colors for ARSA expression ranges from white (<1.5 fold the physiological level) to dark purple (100-fold the physiological level).",
    "ncbi_link": "ARSA: 410"
  },
  {
    "caption": "(E) ARSA activity in the spinal cord of individual LV.GFP- (n=4 blocks/animal, 2-3 replicates) and LV.hARSA-injected NHPs (n=2-4 blocks/animal; n=10 and n=11 total blocks for study group 1 and study group 2, respectively). Graph on the right represent the summary of ARSA activity in each treatment group. One-way ANOVA and Dunnet's multiple comparison test. * p<0.05 versus pilot group.",
    "ncbi_link": "ARSA: 410"
  },
  {
    "caption": "(F) ARSA activity in the sciatic nerve of LV.GFP- (n=2) and LV.hARSA-injected NHPs (n=3). In B-F data are expressed as floating bars (line at mean).",
    "ncbi_link": "ARSA: 410"
  },
  {
    "caption": "(G) ARSA activity in the cerebrospinal fluid (CSF) of UT/LV.GFP (n=3) and LV.hARSA-injected NHP (n=5). Data are expressed as mean±SEM. Student t-test, *p=0.035.",
    "ncbi_link": "ARSA: 410"
  },
  {
    "caption": "(A) Vector copy number (VCN) indicating the distribution of integrated LV genome along the rostro-caudal axis (slices 7-19) in LV.hGALC-injected NHPs (JT02 and JV02) assessed by qPCR. Each dot represent the VCN measured in one block within the slice. Lower threshold (dotted line): VCN<0.001, corresponding to CT>37.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(B) GALC mRNA expression along the rostro-caudal axis of JT02 (slices 7-13) is expressed as fold increase to region-matched blocks of the contralateral hemisphere (dotted line, y=1). Data are expressed as floating bars (min to max, line at mean; n=4-8 blocks/slice). Arrows on x axis in A and B indicate the injection sites.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(A) Specific GALC enzymatic activity in single brain slices of WT untreated (UT; white bars, physiological levels), WT LV.hGALC-treated (JV02) and Krabbe-affected LV.hGALC-treated (JV02) animals (filled grey bars, injected hemisphere; striped grey bars, contralateral hemisphere). Two-way ANOVA followed by Bonferroni's multiple comparison tests; *p<0.05, **p<0.01 vs matched slices of WT UT.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(B-C) Summary of GALC activity in brain (B) samples from JT02 and JV02, as well as from WT and Krabbe UT controls. Data in A-C are represented as floating bars (min to max, line at mean; n=2-6 blocks/slice). Number of blocks analysed/animal: 16 (WT UT), 24 (JT02), 22 (JV02). GALC activity in Krabbe UT samples is < 0.001 nmol/h*mg; n=3 blocks. Kruskal-Wallis test and Dunn's multiple comparison test; *p<0.05, ***p<0.001 vs WT UT.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(B-C) Summary of GALC activity in spinal cord (C; n=3 blocks/animal) samples from JT02 and JV02, as well as from WT and Krabbe UT controls. Data in A-C are represented as floating bars (min to max, line at mean; n=2-6 blocks/slice). Number of blocks analysed/animal: 16 (WT UT), 24 (JT02), 22 (JV02). GALC activity in Krabbe UT samples is < 0.001 nmol/h*mg; n=3 blocks. Kruskal-Wallis test and Dunn's multiple comparison test; *p<0.05, ***p<0.001 vs WT UT.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(D) Chromatographic profile of GALC in selected brain slices and spinal cord (SC) tissue of untreated (UT) WT and LV.hGALC-treated Krabbe NHP (JT02). Extracts were run through a Sephadex S-300 gel filtration column. Fractions (0.2 ml) were assayed for enzyme activity using MUGAL substrate in the presence () or absence of 11µM AgNO3 (●).",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(E) GALC activity in the CSF of JT02 (pre- and post-treatment) and JV02 (post-treatment). Dots represent technical replicates.",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "(F) Beginning at two months (m) of age, animals were evaluated monthly for motor performance using a modified Bayley's scale for infant development. For the study animals (JV02 and JT02), scores are reported as pre-surgery and post-surgery. Historical data for normal and affected animals are presented as means plus one standard deviation. Affected animals score significantly lower than normal animals at any age considered. JT02's motor scores increase over time post LV.GALC injection, being close to the mean observed in normal juveniles at 5 months. Historical data are analyzed by two-way ANOVA and Bonferroni posttests, p<0.05 at 6m, p<0.001 at all other ages. n=5-20 animals/group, except for normal animals at 6 months (n=1).",
    "ncbi_link": "GALC: 2581"
  },
  {
    "caption": "F Visualization of infected region. E. coli FM15  was inoculated at the center of a semi-solid agar plate and the reporter phage M13-sfGFP was inoculated 1-cm away from the center. Fluorescence images were captured after overnight incubation using FITC  channel and an exposure time of 200 ms. Scale bar represents 1 cm. G Relative fluorescence intensity at the center and edge positions of the infection  zone as shown in (F). The relative intensity was obtained by dividing the detected values with the maximum value of green fluorescence intensity on the plate. Data represent mean values ± s.d. for three values of the center and six values of the edge from three biological replicates. Two-tailed t-test was used to compare two groups. ***, p = 0.0005.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B Microscopic  images of E. coli FM15  cells carrying plasmids with gfp  gene downstream of the psp  promoter with or without wild-type M13 phage infection. Scale bar: 1 μm.",
    "ncbi_link": "gfp: 
psp: "
  },
  {
    "caption": "E Activity in cells of T7 RNAP  and its mutants from the SPACE  experiment in (D). Two clones of the ancestor and five clones of the mutants obtained from the evolution towards 1D8  recognition were measured by in vivo transcriptional assay  Two-tailed t-test was used to compare the two groups. ***, p=0.0001. Data represent mean values ± s.d..",
    "ncbi_link": "RNAP: 1261050"
  },
  {
    "caption": "D Expression  activity of 10 RNAP  mutants on T7  promoter and 10 promoter variants measured by in vivo transcriptional assay. Mutants are arranged in the same order as their original target promoters listed on the left side of the heatmap. Data are normalized so that the activity of wild-type RNAP  on the T7 promoter is 100; the mean for three biologically independent replicates is shown",
    "ncbi_link": "RNAP: 1261050"
  },
  {
    "caption": "(D) CHO  cells engineered to transiently express SNAP-mTOR, SNAP-RAPTOR, and SNAP-RICTOR  (Gautier et al., 2008) were incubated with the nuclear  export inhibitor  leptomycin B (LMB) (6.4 ng/mL) for six hours at 37°C. Cells were labeled with TMR-Star (1 μM) for 30 min, washed and then imaged. This experiment demonstrated that mTOR, RAPTOR, and RICTOR  accumulated in the nucleus  after LMB  treatment. Scale bars, 10μm.",
    "ncbi_link": "mTOR: 
RAPTOR: 
RICTOR: 
SNAP: "
  },
  {
    "caption": "(B) Cultured human keratinocytes  (YF29  passage III) treated with rapamycin  maintained a basal phenotype as shown by the expression of several basal (KRT14, BNC1) and terminal differentiation markers (SPINK5, IVL, KRT1, KRT10) using  quantitative PCR (left panel) and Western blotting (right panel). Data are presented as the mean (n = 2 biological replicates).",
    "ncbi_link": "BNC1: 646
IVL: 3713
KRT1: 3848
KRT10: 3858
KRT14: 3861
SPINK5: 11005"
  },
  {
    "caption": "D. PCoA of the rectal bacterial 16S rRNA gene sequences based on the weighted UniFrac distance matrix.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "PCoA, based on the weighted UniFrac distance matrix, of the bacterial 16S rRNA gene sequence data for the rumen, ileum, and colon, shown for the different segments of the gastrointestinal tract (B)",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "C. PCoA, based on the weighted UniFrac distance matrix, of the bacterial 16S rRNA gene sequence data or the rumen, ileum, and colon, combined data (C). D. Microbial dissimilarity (calculated based on the weighted UniFrac distance matrix, 100 values in each group) between the male and CtM groups in the different intestinal compartments. The lines, boxes, and whiskers in the box plot diagrams represent the median, first and third quartiles, and min-to-max distribution of replicate values, respectively. ",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "C. PCoA, based on the weighted UniFrac distance matrix, of the bacterial 16S rRNA gene sequence data for the luminal contents of the ileum and colon, shown according to the different diets and antibiotic treatment.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "C. PCoA, based on the weighted UniFrac distance matrix, of the bacterial 16S rRNA gene sequence data for the luminal contents of the ileum and colon.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "F. PCoA, based on the weighted UniFrac distance matrix, of the bacterial 16S rRNA gene sequence data for the luminal contents of the ileum and colon are shown. The body weight gain data are presented as a percentage of the initial body weight. The fat weight data are presented as a percentage of the body weight.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "(D) Similar BRET experiment showing the Rab7-pool of PI4P both in control HEK293-AT1 cells and in two clones of cells with PI4K2A deletion (#20 and #26). Means ± S.E.M. are shown from three experiments performed in triplicates.",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "(A) BRET measurement of PI4P in Rab7 compartment in parental and PI4K2A K/O cells after expression of HA-tagged PI4K2A or its kinase-dead mutant. Means ± S.E.M. are shown from three experiments performed in triplicates.",
    "ncbi_link": "HA: 
PI4K2A: 55361"
  },
  {
    "caption": "(C) Distribution of GFP-Rab7 in parental (left panels) and two clones of PI4K2A K/O cells. Representative pictures show tubulation in the K/O cells reminiscent of those seen in wild-type cells expressing the GTP-locked Rab7Q67L mutant. Scale bars are 10 µm.",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "(C) Quantification of the changes in BRET experiments. Here the BRET sensor contained the PLCδ1PH-fused to Sluc and the Venus targeted with Rab7 expressed from a single vector and it was co-transfected with the Rab7-targeted FRB (tagged with iRFP) and the FKBP12-fused PIP5Kγ in which the CFP was mutated to eliminate its fluorescence (CFP*). Recruitment of the PIP5Kγ but not its kinase-dead version caused an increase in the BRET signal indicating the increased PI(4,5)P2 in this compartment (means ± S.E.M., from three separate experiments performed in triplicates).",
    "ncbi_link": "CFP: 
iRFP: 
Sluc: 
Venus: 
FKBP12: 2280
PIP5Kγ: 23396
Rab7: 404007"
  },
  {
    "caption": "(D) PI(4,5)P2 increases were larger when the Venus part of the BRET sensor was targeted with the GTP-locked form of Rab7 (Q67L) and was negligible with the GDP-locked form of Rab7 (N125I) in the BRET construct. Also note that the Rab7 wild-type-based BRET signal slowly returned toward the green trace consistent with Rab7 falling off from the membrane both in the BRET and the recruiting constructs (means ± S.E.M., from three separate experiments performed in triplicates).",
    "ncbi_link": "Venus: 
Rab7: 404007"
  },
  {
    "caption": "(E) The response of PI4K2A K/O cells was significantly reduced Means ± S.E.M. are shown from three experiments performed in triplicates.",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "(A) Representative confocal images of HEK293-AT1 cells, which show that treatment with OSW1 (20 nM), a drug that inhibits the cholesterol-PI4P transport protein, OSBP, causes accumulation of PI4P in the Golgi and in the endosomes (upper panels). Note that the accumulation is much reduced in the endosome but less so in the Golgi in the PI4K2A K/O cells. Scale bars: 20 µm",
    "ncbi_link": "PI4K2A: 55361"
  },
  {
    "caption": "(B) Quantification of these changes by BRET analysis. The PI4P-Rab7 BRET sensor construct was transfected into the respective cell lines and the cells treated with OSW1 (20 nM) for the indicated times. The BRET ratios were expressed relative to those of DMSO treated cells. Data information: Means ± S.E.M. are shown from three experiments performed in triplicates.",
    "ncbi_link": "Rab7: 404007"
  },
  {
    "caption": "(C) Detection of endosomal PI(4,5)P2 in cells pre-treated with OSW1 for 1 h in serum-free medium using confocal microscopy and the PLCδ1PH-GFP PI(4,5)P2 reporter. Angiotensin II (AngII, 100 nM) (a Gq and PLC-activating agonist) was used to liberate the PLCδ1PH-GFP PI(4,5)P2 reporter from the PM, which was necessary to detect the endosomal PI(4,5)P2. The signal is transient as the AngII receptors show desensitization. Note the reduced signal in the two PI4K2A K/O clones. Scale bars: 20 µm.",
    "ncbi_link": "PLC: 
Gq: 2776
PI4K2A: 55361"
  },
  {
    "caption": "(D) Quantification of the same changes by BRET analysis in wild-type cells using the PI(4,5)P2 sensor with Rab7-Q67L-targeting. Note the transient signal increase after AngII stimulation only in cells treated with OSW1. (E) This increase is barely detectable in the PI4K2A K/O cells. D Data information: Means ± S.E.M. are shown from three experiments performed in triplicates. The values in (D) and (E) were measured in the same 96-well plate at the same time.",
    "ncbi_link": "PI4K2A: 55361
Rab7: 404007"
  },
  {
    "caption": "(A) BRET experiment in parental HEK293-AT1 cells in OSW1-pretreated cells after RNAi mediated knock-down of PIP5Kβ or PIP5Kγ. (means ± S.E.M. from three experiments, each performed in triplicates). Note the reduced response in the PIP5Kγ knock-down cells and the slight reduction in the case of PIP5Kβ knock-down. (B) Areas below the curves calculated from the time of rapamycin addition for each of the three separate experiments shown in panel A (means ± S.E.M., n=3). One-way ANOVA with Dunnett's multiple comparisons was used for statistical analysis (* P=0.0241; **P=0.0088). ( ",
    "ncbi_link": "PIP5Kβ: 8395
PIP5Kγ: 23396"
  },
  {
    "caption": "(D) Increased appearance of GFP-LC3 positive vesicles in PI4K2A K/O cells and reduced acidification of the LC3-positive vesicles using the GFP-mCherry-LC3 reporter. Cells were transfected with the indicated constructs for one day and observed by confocal microscopy. Scale bars: 20 µm. (E) Quantification of the LC3 positive vesicles. (n = 67, 34, 26, 13, 30, 27 for the various groups, respectively from left to right). *** designates P < 0.0001 using unpaired t-test. The same data set was also analyzed with the non-parametric Mann-Whitney test showing a P = 0.0004 and 0.0012 for #20 and #26 clones relative to control, respectively. (F) Co-localization analysis using the Pearson coefficient (n = 31, 21 and 14 cells analyzed for the different groups from left to right). *** designates P < 0.0001 using unpaired t-test. The same data set was also analyzed with the non-parametric Mann-Whitney test showing a P value < 0.0001 for both groups. ",
    "ncbi_link": "GFP: 
LC3: 
mCherry: 
PI4K2A: 55361"
  },
  {
    "caption": "(A, B) Distribution of mCherry-GFP-LC3 in HEK293-AT1 cells (without starvation) after treatment with control siRNA (A) or siRNA for PIP5Kγ (PIP5K1C). Scale bars: 20 µm. Note the massive tubulation of the LC3 compartment in some of the knocked-down cells (B, lower images, scale bar: 10 µm). (C) Comparison of Pearson coefficients from cells treated with control or PIP5Kγ RNAi. For statistical analysis the unpaired t-test was used (n = 50 and 45 cells for control a PIP5Kγ knock down groups, respectively; *** P< 0.0001). (D) Representative confocal images of live HEK293-AT1 cells expressing GFP-Rab7 treated with control or PIP5Kγ RNAi. Note the tubulation in the PIP5Kγ RNAi-treated cells. Scale bars: 10 µm. ",
    "ncbi_link": "GFP: 
LC3: 
mCherry: 
PIP5K1C: 23396
PIP5Kγ: 23396"
  },
  {
    "caption": "(A) HEK293-AT1 cells were transfected with PLEKHM1-GFP-Rab7 along with CFP-FKBP-PIP5Kγ and iRFP-FRB-Rab7 constructs for one day and examined live by confocal microscopy. Representative cells show reduced PLEKHM1 localization when PIP5Kγ was recruited to the Rab7 endosomes (lower row images). (B) This response is reduced in PI4K2A K/O cells. ( Data information: Scale bars: 20 µm.",
    "ncbi_link": "CFP: 
GFP: 
iRFP: 
FKBP: 2280
PI4K2A: 55361
PIP5Kγ: 23396
PLEKHM1: 9842
Rab7: 404007"
  },
  {
    "caption": "(C) Quantification of these changes by BRET analysis where the full-length PLEKHM1 was fused to Sluc and Venus was fused to Rab7 in the BRET construct. For PIP5Kγ recruitment a mutant dark CFP(W66A)-FKBP-PIP5Kγ was used with an iRFP-FRB-Rab7. BRET values were normalized to those of DMSO treated cells. Comparisons were made for parental (blue) and PI4K2A K/O (green and orange) cells. (D) Similar BRET analysis where the PLEKHM1 was replaced by either RILP or Vps35 in the BRET construct. D Data information Means ± S.E.M. are shown from three experiments performed in triplicates.",
    "ncbi_link": "CFP: 
iRFP: 
Sluc: 
Venus: 
FKBP: 2280
PI4K2A: 55361
PIP5Kγ: 23396
PLEKHM1: 9842
Rab7: 404007
RILP: 83547
Vps35: 55737"
  },
  {
    "caption": "(A) Number of cell corpses at the L1 stage of development per 100 animals carrying the neurotoxic mec‐4(d) or deg‐3(d) alleles in SNT‐1‐deficient mutants. For mec‐4(d) mutant animals, bars denote touch receptor neuron corpses. For deg‐3(d)mutants, bars denote inner labial neuron 1 (L1) sensory neuron and PVC interneuron corpses.",
    "ncbi_link": "deg‐3: 3565200
mec‐4: 181728
SNT‐1: 174120"
  },
  {
    "caption": "(B) Expression of a full‐length MEC‐4::GFP reporter fusion under the control of the mec‐4 promoter in touch receptor neurons of wild‐type, snt‐1 and unc‐57 mutant animals. Representative photos of touch receptor neuron cell bodies are shown. Bar denotes 6 μm. The quantification (%) of GFP signal intensity from the animals examined is graphed below (n=100 neurons per assay; P0.05 compared with wild type; t‐test).",
    "ncbi_link": "MEC‐4: 181728
snt‐1: 174120
unc‐57: 268228"
  },
  {
    "caption": "(C) Percentage of SNT‐1‐deficient animals that survive near‐lethal treatment with sodium azide. This chemical inhibits the activity of the respiratory electron transport complex IV (cytochrome C oxidase) and simulates hypoxia.",
    "ncbi_link": "SNT‐1: 174120"
  },
  {
    "caption": "(D) Number of touch receptor neuron corpses, at the L1 stage of development, per 100 animals carrying the neurotoxic mec-4(d) or deg‐3(d) alleles in UNC‐57‐deficient animals.",
    "ncbi_link": "deg‐3: 3565200
mec-4: 181728
UNC‐57: 268228"
  },
  {
    "caption": "(E) Percentage of UNC‐57‐deficient animals that survive after the hypoxia‐inducing treatment with sodium azide.",
    "ncbi_link": "UNC‐57: 268228"
  },
  {
    "caption": "(F) Number of touch receptor neuron corpses, at the L1 stage of development, per 100 animals carrying the neurotoxic mec‐4(d) or deg‐3(d) alleles together with lesions in genes encoding key proteins that participate in all four steps of clathrin‐mediated endocytosis. UNC‐11 and DPY‐23 are adaptor proteins required for the formation of clathrin‐coated pits, DYN‐1 is a GTPase necessary for fission of clathrin‐coated vesicles and UNC‐26 participates in the uncoating of vesicles. Error bars denote s.e.m. values (n>250 for all populations examined; P0.001, compared with wild‐type animals, unpaired t‐test).",
    "ncbi_link": "deg‐3: 3565200
DPY‐23: 180713
DYN‐1: 181644
mec‐4: 181728
UNC‐11: 171952
UNC‐26: 178284"
  },
  {
    "caption": "(A) Confocal images of touch receptor neurons expressing a pmec‐17APS‐2GFP reporter transgene. During early necrosis, the number of APS‐2::GFP puncta, corresponding to clathrin‐coated pits and vesicles, in touch receptor neurons ofmec‐4(d) animals does not change significantly, whereas at later stages it decreases. A similar decrease is also observed in unc‐57(e1190) mutants, defective for clathrin‐mediated endocytosis.",
    "ncbi_link": "APS‐2: 184091
mec‐4: 181728
unc‐57: 268228"
  },
  {
    "caption": "(B) Confocal images of touch receptor neurons expressing a pmec‐7GFP::RAB‐5 reporter transgene. The number of fluorescent puncta that correspond to early endosomes in touch receptor neurons of mec‐4(d) animals significantly increases during early necrosis, whereas it declines later.",
    "ncbi_link": "mec‐4: 181728
RAB‐5: 172755"
  },
  {
    "caption": "(C) Confocal images of touch receptor neurons expressing a pmec‐7GFP::RAB‐11 reporter transgene. The number of GFP::RAB‐11 puncta that correspond to recycling endosomes in touch receptor neurons of mec‐4(d) animals increases early during cell death, while it declines as degeneration proceeds. Both early and recycling endosomes tend to accumulate around a swollen structure that is probably the nucleus. Bars denote 4 μm. Error bars denote s.e.m. values (n>250 for all populations examined; P0.001, compared with control animals, unpaired t‐test).",
    "ncbi_link": "mec‐4: 181728
RAB‐11: 4363014///171601"
  },
  {
    "caption": "Endocytosis functions together with lysosomal proteolysis to facilitate necrotic cell death. (A) Depletion of synaptotagmin (SNT‐1) or endophilin (UNC‐57) does not further suppress MEC‐4(d)‐induced necrosis in cad‐1 mutants with reduced cathepsin activity or with V‐ATPase dysfunction (B, C).",
    "ncbi_link": "cad‐1: 
MEC‐4: 181728
SNT‐1: 174120
UNC‐57: 268228"
  },
  {
    "caption": "(A) Synaptotagmin (SNT‐1) deficiency further suppresses MEC‐4(d)‐induced necrosis in animals with impaired autophagy.",
    "ncbi_link": "MEC‐4: 181728
SNT‐1: 174120"
  },
  {
    "caption": "(B) Endophilin dysfunction enhances suppression of necrosis in mec‐4(d);lgg‐1(RNAi) animals, where autophagy is impaired. Error bars denote s.e.m. values (n>250 for all populations examined; P0.01, compared with single mutant control animals, unpaired t‐test).",
    "ncbi_link": "lgg‐1: 174050
mec‐4: 181728"
  },
  {
    "caption": "(A) Depletion of the kinesin 1 heavy chain UNC‐116 suppresses necrosis induced by both mec‐4(d) and deg‐3(d) toxic alleles.",
    "ncbi_link": "deg‐3: 3565200
mec‐4: 181728
UNC‐116: 176179"
  },
  {
    "caption": "(B) Expression of a full‐length MEC‐4::GFP reporter fusion under the control of the mec‐4 promoter in touch receptor neurons of wild‐type, unc‐116 and unc‐104 mutant animals. Representative photos of touch receptor neuron cell bodies are shown. Bar denotes 6 μm. The quantification (%) of GFP signal intensity from the animals examined is graphed below (n=100 neurons per assay; P0.05 compared with wild type; t‐test).",
    "ncbi_link": "mec‐4: 181728
unc‐104: 174144
unc‐116: 176179"
  },
  {
    "caption": "(C) Percentage of unc‐116 animals that survive after treatment with sodium azide.",
    "ncbi_link": "unc‐116: 176179"
  },
  {
    "caption": "(D) Depletion of the monomeric kinesin UNC‐104 protects neurons against MEC‐4(d)‐induced degeneration.",
    "ncbi_link": "MEC‐4: 181728
UNC‐104: 174144"
  },
  {
    "caption": "(E) unc‐104 mutant animals are more resistant to hypoxic death induced by sodium azide.",
    "ncbi_link": "unc‐104: 174144"
  },
  {
    "caption": "(F) Combined inactivation of endocytosis and kinesin‐mediated intracellular trafficking does not enhance protection of touch receptor neurons against MEC‐4(d)‐induced degeneration. Error bars denote s.e.m. values (n>250 for all populations examined; P0.001, compared with control animals, unpaired t‐test).",
    "ncbi_link": "MEC‐4: 181728"
  },
  {
    "caption": "Genetic interaction between kinesin‐mediated intracellular trafficking and cellular proteolytic pathways mediating necrotic cell death. Dysfunction of either kinesin 1 heavy chain (UNC‐116) or the monomeric kinesin UNC‐104 does not significantly enhance suppression of neurodegeneration in aspartyl protease‐deficient mutant animals (A, B), in animals with compromised lysosomal acidification (C, D), or in calpain protease‐deficient mutants animals (E, F). Error bars denote s.e.m. values (n>250 for all populations examined; P>0.5, compared with single mutant control animals, unpaired t‐test).",
    "ncbi_link": "UNC‐104: 174144
UNC‐116: 176179"
  },
  {
    "caption": "(A) Kinesin 1 heavy chain (UNC‐116) deficiency.",
    "ncbi_link": "UNC‐116: 176179"
  },
  {
    "caption": "(B) Monomeric kinesin UNC‐104 deficiency. In both cases, no significant synthetic protection of neurons is observed in LGG‐1/LC3‐depleted animals with impaired autophagy. Error bars denote s.e.m. values (n>250 for all populations examined; P>0.5, compared with single mutant control animals, unpaired t‐test).",
    "ncbi_link": "LGG‐1: 174050
LC3: 177989///174050
UNC‐104: 174144"
  },
  {
    "caption": "Chromogenic WM-ISH of miR-9 using miR-9 LNA 5'-Dig observed at different stages during development; longitudinal view, anterior to the left.",
    "ncbi_link": "miR-9: 100033553"
  },
  {
    "caption": "Transverse section of double fluorescent WM-ISH for her6 (green) and mir-9-4 (magenta) imaged in fixed embryo at 31hpf; scale bar 30μm.",
    "ncbi_link": "mir-9-4: 100033555"
  },
  {
    "caption": "Representative examples of triple fluorescent whole mount WM-ISH labelling of gfap (green), elavl3 (magenta) and her6 (grey) domains of expression (top panels) in hindbrain rhombomere6 (r6) in wild-type embryo observed at 34hpf; merged images indicate how the her6 expression domain overlaps with the progenitor zone (NP=gfap(+)/elavl3(-)), transition zone (T=gfap(+)/elavl3(+)) and neurogenic zone (N=gfap(-)/elavl3(+)); (bottom-right panel) schematic representation showing the her6 domain spanning the NP, T and N zones with quantification of distances from dorsal; transversal view; annotations denote dorsal (D) and ventral (V); scale bar 30μm.",
    "ncbi_link": "elavl3: 30732
gfap: 30646
her6: 30288"
  },
  {
    "caption": "Single molecule fluorescent in situ hybridization (smFISH) showing her6 (green), elavl3 (magenta) and dapi nuclear staining (blue) obtained from hindbrain (r6) sections of wild type embryo at 34hpf; head arrows indicates examples of co-existence of transcriptional active sites for her6 and elavl3; scale bar 3μm.",
    "ncbi_link": "elavl3: 30732
her6: 30288"
  },
  {
    "caption": "Triple fluorescent WM-ISH for gfap (green) and elavl3 (magenta) and her6 (grey) in the hindbrain (r6) of CTRL (top) and MBSm (bottom) embryos at 52hpf; dorsal (D); ventral (V); scale bar 30μm. Magnification of inset from merged gfap/elavl3 in (c) showing CTRL (top) and MBSm (bottom) embryos with corresponding NP/T/ N and NP/T zones respectively; dorsal (D); ventral (V); scale bar 30μm. Normalized intensity mean of elavl3 and gfap along the DV axis spanning the NP/T/N zones in CTRL and NP/T zones in MBSm respectively; region of interest (ROI) delineates high elavl3 versus gfap in CTRL (T and N zones) while in MBSm only the T zone is observed, overlap of elavl3 and gfap intensity mean peaks.",
    "ncbi_link": "elavl3: 30732
gfap: 30646
her6: 30288"
  },
  {
    "caption": "Normalized mean of elavl3 and gfap intensities in ROI observed in: (f) uninjected (UI) (5 embryos, 62 slices), (g) control (CTRL) (5 embryos, 35 slices) and (h) MBSm (8 embryos, 62 slices) conditions; bars represent mean and SEM; multiple t-test with Benjamini, Krieger and Yekuteli discovery, significance: p<0.05*, p<0.001***, p<0.0001****.",
    "ncbi_link": "elavl3: 30732
gfap: 30646"
  },
  {
    "caption": "Transverse sections of double fluorescent WM-ISH for gfap (green) and neuroD4 (blue) in the hindbrain (r6) of CTRL (top) and MBSm (bottom) embryos at 52hpf; dorsal (D); ventral (V); scale bar 30μm.",
    "ncbi_link": "gfap: 30646
neuroD4: 266958"
  },
  {
    "caption": "Chromogenic WM-ISH showing neuroD4 expression intensity in: uninjected (UI) 51/56 embryos (91%), CTRL 50/54 embryos (93%) and mutant (MBSm); 36/65 embryos (55 %); longitudinal view, scale bar 100μm.",
    "ncbi_link": "neuroD4: 266958"
  },
  {
    "caption": "C Representative images and quantitative analyses of ACE2 immunohistochemical staining in lungs of age-matched wild type and G3 Terc-/- mice (n = 3-4 mice per group). Scale bar, 200 µm.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "D Double-marker immunofluorescence and quantitative analyses of ACE2 intensity level in type II pneumocytic pro-SP-C-positive and CD31-positive endothelia in lungs of age-matched wild type and G3 Terc-/- mice (n = 3-4 mice per group). Scale bar, 100 µm. a.u. = arbitrary units.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "A Immunofluorescence showing gammaH2AX foci in MEFs Trf2F/F at the indicated time points following 4OHT treatment and consequent TRF2 knockout. Scale bar, 25 µm. B RT-qPCR detection of Ace2 mRNA expression levels in MEFs Trf2F/F treated as in A (n = 3 independent experiments).",
    "ncbi_link": "Ace2: 70008
Trf2: 21750
TRF2: 21750"
  },
  {
    "caption": "C Immunofluorescence showing gammaH2AX foci in HeLa shTRF2 cells at the indicated time points following doxycycline treatment and consequent TRF2 knockdown. Scale bar, 25 µm. D RT-qPCR detection of ACE2 mRNA expression levels in HeLa shTRF2 cells treated as in C (n = 6 independent experiments).",
    "ncbi_link": "ACE2: 59272
TRF2: 7014"
  },
  {
    "caption": "E Representative immunofluorescence images of 53BP1 staining in liver from Trf2F/F mice treated with tamoxifen (to induce TRF2 loss and telomere uncapping) or vehicle. The animals as been injected also with PBS. Scale bar, 10 µm. F RT-qPCR detection of Ace2 mRNA expression levels in livers of mice treated as in E (n = 5-7 mice per group).",
    "ncbi_link": "Ace2: 70008
Trf2: 21750
TRF2: 21750"
  },
  {
    "caption": "B Relative luciferase activity in HeLa shTRF2 following ionizing radiation (5 Gy) or TRF2 knockdown upon doxycycline-induced shTRF2 expression (n=3 independent experiments). Error bars represent the s.e.m. *P<0.05. Two-way paired ANOVA.",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "A Immunofluorescence showing gammaH2AX foci in Trf2F/F MEFs at the indicated time points following 4OHT treatment and consequent TRF2 knockout and treated with DMSO or ATMi. Scale bar, 25 µm. B RT-qPCR detection of Ace2 mRNA expression levels in MEFs Trf2F/F treated as in A (n = 3 independent experiments).",
    "ncbi_link": "Ace2: 70008
Trf2: 21750
TRF2: 21750"
  },
  {
    "caption": "C Representative immunofluorescence images of 53BP1 staining in liver from Trf2F/F mice treated with tamoxifen (to induce telomere uncapping) or vehicle and injected with the indicated ASOs or PBS as control. Scale bar, 10 µm. D RT-qPCR detection of Ace2 mRNA levels in livers of mice treated as in C (n = 5-8 mice per group).",
    "ncbi_link": "Ace2: 70008
Trf2: 21750"
  },
  {
    "caption": "E Representative microphotographs and quantitative analyses of ACE2 immunohistochemical staining in lungs of age-matched wild type and G3 Terc-/- mice, treated with the indicated ASOs (n = 4-9 mice per group). Scale bar, 200 µm.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "F Double-marker immunofluorescence and quantitative analyses of ACE2 intensity level in type II pneumocytic pro-SP-C-positive cells in lungs of age-matched wild type and G3 Terc-/- mice, treated with the indicated ASOs (n = 4-9 mice per group). Scale bar, 100 µm. a.u. = arbitrary units.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "(d) Parkin was overexpressed in young and senescent MEFs using adenovirus-mediated transduction for the in vitro cell-based bioassay to assess the ability to clear damaged mitochondria. Mitochondrial content after 24 h of treatment with 20 μM CCCP was assessed by flow cytometry for MitoTracker Green FM. Results from four independent experiments performed in duplicate are shown. MEFs at passage 3 and passage 9 were used as young and senescent MEFs, respectively.",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "(g) Representative images of GFP-LC3 expressing MEFs treated with 20 μM CCCP for 10 h before the immunostaining of mitochondria with anti-TOM20 (red); original magnification, × 400 and × 1,000; scale bar, 100 μm and scale bar, 15 μm. Line scans below the images indicate colocalization between LC3 (green) and mitochondria (red) and correlate to the arrows drawn in the images. WHL indicates whole-heart lysate. Data are shown as the means±s.d. *P0.05; **P0.01 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(a) The senescence-associated molecules p53, p21, p16, H-Ras 12V and Rb were overexpressed in MEFs by retrovirus-mediated transduction. After puromycin selection, mitophagy induction was performed with treatment of 20 μM CCCP 24 h after adenovirus-mediated Parkin expression. Mitochondrial content 24 h after mitophagy induction was assessed by flow cytometry for MitoTracker Green FM. Results are shown from four independent experiments performed in duplicate.",
    "ncbi_link": "p21: 12575
p16: 12578
H-Ras: 15461
Parkin: 50873
Rb: 19645
p53: 22059"
  },
  {
    "caption": "(c) Mitochondrial content of H-Ras 12 V expressing WT, p53−/− and p21−/− MEFs was assessed by flow cytometry 24 h after mitophagy induction. Results are shown from four independent experiments performed in duplicate.",
    "ncbi_link": "p21: 12575
H-Ras: 15461
p53: 22059"
  },
  {
    "caption": "(d) Mitochondrial content of WT and p53−/− MEFs was assessed by flow cytometry 24 h after mitophagy induction. WT and p53−/− MEFs were transfected with control or p53-specific siRNAs or cultured in complete medium for 24 h in the presence or absence of 20 μM pifithrin-α before mitophagy induction. Results are shown from four independent experiments performed in duplicate.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(e) Murine HL-1 cardiac myocytes were infected with retrovirus vectors encoding p53, p21 or p16 and after puromycin selection, underwent mitophagy induction. Mitochondrial content is assessed by flow cytometry from four independent experiments performed in duplicate are shown.",
    "ncbi_link": "p21: 12575
p16: 12578
p53: 22059"
  },
  {
    "caption": "(f) HL-1 cells were transfected with control, p53, p21 or p16-specific siRNAs, followed by treatment with 0.02 μM DOX and mitophagy induction. Mitochondrial content is assessed by flow cytometry from four independent experiments performed in duplicate.",
    "ncbi_link": "p21: 12575
p16: 12578
p53: 22059"
  },
  {
    "caption": "(g) CCCP-induced recruitment of Parkin and expression of Mfn1 and Drp1 in DOX-treated WT, p53−/− and p21−/− mice were determined by immunoblotting of the heartmitochondria-rich fraction. Representative immunoblots are shown from four independent experiments. Data are shown as the means±s.d. *P0.05; **P0.01 (two-tailed unpaired Student's t-test).",
    "ncbi_link": "p21: 12575
p53: 22059"
  },
  {
    "caption": "(a) Whole-cell lysates of HL-1 cells treated with 0.02 μM DOX and transfected with FLAG-tagged Parkin or the FLAG-empty vector were immunoprecipitated with the anti-Flag-M2 antibody and blotted with anti-p53 and Flag antibodies.",
    "ncbi_link": "Parkin: 50873
p53: 22059"
  },
  {
    "caption": "(d) Schematic representation of N-terminally FLAG-tagged WT Parkin and various mutants of Parkin. (e) The association of endogenous p53 with various Parkin mutants in DOX-treated HeLa cells. The immunoprecipitation assay revealed that the RING0 domain was essential for the interaction with p53.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(f) Schematic representation of the GST-p53 fusion proteins. (g) GST pull-down assays using GST-p53 fusion proteins and in vitro transcribed/translated FLAG-Parkin. Residues 81-160 of p53 were sufficient to bind Parkin.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(a) HL-1 cells transfected with control or p53-specific siRNAs no.1 and cultured in complete medium for 24 h in the presence or absence of 0.02 μM DOX. After treatment with 20 μM CCCP for 6 h, the fractionation experiment was performed. Endogenous Parkin translocation to mitochondria and ubiquitination were assessed by immunoblotting. Representative immunoblots are shown from three independent experiments.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(c,d) Representative images of YFP-Parkin overexpressing p53−/− HCT116 cells re-transfected with WT p53 and various mutants of p53 and treated with 60 μM CCCP for 8h (c) and 36 h (d) before the immunostaining of mitochondria with anti-TOM20 (red) and endogenous poly-ubiquitin with a specific antibody FK-2 (white); original magnification, × 630; scale bar, 20 μm.",
    "ncbi_link": "Parkin: 5071
p53: 7157"
  },
  {
    "caption": "(g) Maximum dP/dt was examined using cardiac catheterization with graded dobutamine infusion in WT and Parkin Tg aged littermates (n=8 per group).",
    "ncbi_link": "Parkin: 50873"
  },
  {
    "caption": "ivMCs induce differentiation of co-cultured intestinal organoids as determined by qRT-PCR for stem cell (Lgr5, Olfm4) and proliferation (Ki67, Pcna) and differentiation markers (Muc2-goblet cells, Krt20-differentiated epithelial cells, Sim and Alpi-enterocytes). Enhanced terminal enterocytic differentiation was checked by villus center markers (Fabp1, Fabp2, G6pc, Leap2) and villus tip markers (Ada, Lama3, Lgals3, Cdh1). (Expression levels normalized to Ubiquitin B (Ubb), ENR parallel set as 1, error bars show sd, each dot represents one technical replicate of one representative experiment). If n = 2 technical replicates, error bars, and mean are not shown.",
    "ncbi_link": "Ada: 11486
Alpi: 76768
Cdh1: 12550
Fabp1: 14080
Fabp2: 14079
G6pc: 14377
Krt20: 66809
Lama3: 16774
Leap2: 259301
Lgals3: 16854
Lgr5: 14160
Ki67: 17345
Muc2: 17831
Olfm4: 380924
Pcna: 18538
Sim: 69983
Ubb: 22187
Ubiquitin B: 22187"
  },
  {
    "caption": "Relative expression of differentiation (Muc2-goblet cells, Krt20-differentiated epithelial cells, Sim and Alpi-enterocytes) and stem (Lgr5, Olfm4) markers in intestinal crypts upon 96 hours cultivation with indicated Bmp (500 ng/ml). (qRT-PCR, expression levels normalized to Ubiquitin B (Ubb), error bars show sd, Untreated parallel set as 1, each dot represents one technical replicate of one representative experiment.).",
    "ncbi_link": "Alpi: 76768
Krt20: 66809
Lgr5: 14160
Muc2: 17831
Olfm4: 380924
Sim: 69983
Ubb: 22187
Ubiquitin B: 22187"
  },
  {
    "caption": "Bmp2 treatment induces the expression of the villus tip markers Nt5e (Cd73 protein). (Graph shows normalized counts determined by RNAseq, n= at least 3 for each treatment, timepoint: 24 hours, error bars denote sd).",
    "ncbi_link": "Cd73: 23959
Nt5e: 23959"
  },
  {
    "caption": "Changes in the expression of villus tip and villus center genes after LDN-193189-4HCl (150 mg/kg) treatment determined by qRT-PCR normalized to β-actin (β-act). (Each dot represents one technical replicate of one representative experiment, error bars show sd.).",
    "ncbi_link": "β-act: 11461
β-actin: 11461"
  },
  {
    "caption": "Induction of shRNA against Smad4 upon the doxycycline (+Dox) treatment (3 days) followed by Bmp2 treatment for additional 24 hours. shRNA activation is visualised by the expression of coupled TdTomato (red), scale bar, 200 μm.",
    "ncbi_link": "Smad4: 17128"
  },
  {
    "caption": "Smad4 knock-down (shRNA-ON) alleviates Bmp2-induced differentiation marked by relative expression of villus tip genes. (qRT-PCR, expression levels normalized to Ubiquitin B (Ubb), each dot represents one technical replicate of one representative experiment, error bars show sd, untreated parallel set as 1, treatment as in 6A).",
    "ncbi_link": "Smad4: 17128
Ubb: 22187
Ubiquitin B: 22187"
  },
  {
    "caption": "Long term (4 weeks) organoid cultivation in the presence of Bmp2 (10 ng/ml) enriches the expression of villus tip genes. (qRT-PCR, expression levels normalized to Ubiquitin B (Ubb), each dot represents one technical replicate of one representative experiment, error bars show sd, untreated parallel set as 1, P2 - collected 4 days after 2nd passage, P4 -collected 4 days after 4th passage).",
    "ncbi_link": "Ubb: 22187
Ubiquitin B: 22187"
  },
  {
    "caption": "qRT-PCR for villus tip genes and villus center genes in freshly established organoids cultivated 24 or 96 hours with Bmp2 (500 ng/ml), Wnt5a (500 ng/ml) or both Bmp2 + Wnt5a (each 500 ng/ml). Whereas Bmp2 induces villus tip genes by its own, it can act synergistically with Wnt5a. For the short-term cultivation, the effect is specific for villus tip genes (notice the different scale in left graphs). (Expression levels normalized to Hmbs, untreated parallel set as 1, each dot represents one technical replicate of one representative experiment, error bars show sd). If n = 2 technical replicates, error bars and mean are not shown.",
    "ncbi_link": "Hmbs: 15288"
  },
  {
    "caption": "Relative  mRNA levels of the  sAPX, 2-Cys Prx, GPXL, and PrxQ genes in response to  BSMV infections at 1, 3 and 5 dpi. The empty vector (EV) was used as a negative control, NbEF1α was used as an internal control. Data information: In (D), error bars indicate mean ± SEM from three independent experiments; * p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001, **** p-value < 0.0001 from Student's t test.",
    "ncbi_link": "sAPX: 
2-Cys Prx: 
EF1α: 
GPXL: 
PrxQ: "
  },
  {
    "caption": "BSMV  accumulation in  2-Cys Prx     or GPXL-silenced  N. benthamiana plants using anti-TGB1  antibody. Empty vector TRV: 00 was used as negative control. Data information: representative data are shown, at least three independent replicates were performed with similar results.",
    "ncbi_link": "2-Cys Prx: 
GPXL: "
  },
  {
    "caption": "Co-localization of γb and NbNTRC during BSMV infection. NbNTRC-mCherry was co-expressed with BSMVγb-GFP (Jiang et al., 2020) in N. benthamiana, and confocal analyses were conducted at 3 dpi, and  chloroplast autofluorescence is displayed as a false-blue color. Scale bars, 20 μm.",
    "ncbi_link": "GFP: 
mCherry: 
NTRC: 
γb: 962674"
  },
  {
    "caption": "Analysis of VSR  activities of  γb  mutants. Infiltrated N. benthamiana leaves co-expressing sGFP  plus γbH85A-3xFlag,  γbH85C-3xFlag or the pGD empty vector (EV) were observed at 5 dpi under long-wave UV illumination for GFP fluorescence. The γb-3xFlag protein served as a positive control. The white dashed circles indicate the infiltrated zone.   Western blot  analysis of the  GFP protein in co-infiltrated  leaves at 5 dpi with anti-GFP  antibody. RbcL  was used as loading control.  Data information:  representative data were shown, and three independent experiments showed a similar result.",
    "ncbi_link": "Flag: 
sGFP: 
γb: 962674"
  },
  {
    "caption": "Effects of  NbNTRC overexpression on BSMV protein accumulation. N. benthamiana leaves  were first infiltrated with Agrobacterium containing various contructs indicated above the panel. After 1.5 dpi, BSMV was inoculated onto the leaves by agroinfiltration. Three days later, total protein was extracted for Western blotting with anti-TGB1 and anti-Flag  antibodies. The uncleaved NTRC with cTP and cleaved NTRC without cTP are marked with black and gray arrows RbcL was a loading control. Data information: representative data are shown and three eplicates similar results.",
    "ncbi_link": "NTRC: "
  },
  {
    "caption": "Effects of  NbNTRC  overexpression on BSMV replication. Movement-deficient  BSMV (RNAα +  RNAγ) was infiltrated into  leaves  that had been agroinfiltrated previously with various constructs indicated above the panel. NbNTRC and viral  γb proteins were detected by  Western blotting with anti-Flag and anti-γb antibodies. Uncleaved  NTRC with cTP and cleaved NTRC without  cTP are marked with black and gray arrows (see Appendix Fig S4).   RT-qPCR analyses of viral RNA accumulation in 4B. NbPP2A was used as an internal control.   Data information: representative data are shown and three eplicates similar results. In (C), error bars indicate mean ± SEM from three independent experiments.",
    "ncbi_link": "NTRC: 
PP2A: 
RNAα: 
RNAγ: "
  },
  {
    "caption": "Left panel: systemic symptoms of N. benthamiana  plants inoculated with BSMV and BSMV γb  mutants. Photographs were taken at 7 dpi. Right panel: schematic representation of inoculated (ino.), older systemic  leaves  (o-SL), and younger systemic leaves (y-SL) in N. benthamiana plants. Scale bars, 2 cm.",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "Western blot analyses of TGB1 and CP accumulation in BSMV and BSMV γb mutant inoculated N. benthamiana leaves. Anti-TGB1 and anti-CP were used for protein detection. Data information: , representative data are shown, and three replicates had similar results. RbcL served as loading control.",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "Effects of  NbNTRC overexpression on infection of BSMV  and BSMV γb mutants. A. tumefaciens harboring the indicated plasmids were infiltrated into N. benthamiana leaves. Note: Agrobacterium containing NbNTRC constructs were diluted 5-fold compared to normal use (OD600 = 0.3). BSMV and the γb mutants were then agroinfiltrated into the same  leaves  at 1.5 dpi. Three days later, Western blots were conducted with anti-TGB1 and anti-Flag antibodies. Uncleaved NTRC with cTP and cleaved  NTRC  without cTP  are marked with black and gray arrows Data information: representative data are shown, and three replicates had similar results. RbcL served as loading control.",
    "ncbi_link": "NTRC: 
γb: 962674"
  },
  {
    "caption": "Left panel: Western blot  detection of  BSMV CP accumulation in N. benthamiana leaves inoculated with  BSMV and γb movement deficient mutants. Leaf  samples were collected from different regions of the same leaf (right panel) Data information: representative data are shown, and three replicates had similar results. RbcL  served as loading control.",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "Effects of γb and γb  mutants on 2-Cys Prx   in  N. benthamiana. Different combinantions of the pGD empty vector (EV) or γb and γb mutants are indicated above the panel. NbNTRC  and γb proteins were detected by Western blotting with anti-Flag  and anti-γb  antibodies under reducing conditions, Western blot analyses of 2-Cys Prx  abundance with anti-2-Cys Prx  antibody under non-reducing conditions. The uncleaved NTRC  with cTP and cleaved  NTRC without  cTP are marked with black and gray arrows, respectively. Data information: representative data are shown, and three replicates had similar results.  RbcL served as loading control.",
    "ncbi_link": "γb: 962674"
  },
  {
    "caption": "Split-LUC assays to determine NbNTRC-2-Cys Prx interactions in N. benthamiana during BSMV infection. NbNTRC-cLUC  and 2-Cys Prx-nLUC  were co-expressed in N. benthamiana leaves  infected with the indicated BSMV derivatives, Bioluminescence  was observed at 3 dpi. The white dashed circles indicate the infiltrated regions.   Quantification of the luciferase signals shown in Figure 6C as assessed by ImageJ software.   Data information: Representative data were shown , and three replicates had similar results. In (D), error bars indicate mean ± SEM (n = 6). c indicate statistically significant differences among different groups (ANOVA, p-value < 0.05).",
    "ncbi_link": "2-Cys Prx: 
LUC: 
NTRC: "
  },
  {
    "caption": "Western blot  analyses to detect LRSV γb in NbNTRC-OE and NbNTRC-KO N. benthamiana  plants challenged with LRSV at 8 dpi. RbcL  was used as the loading control. Data information: representative data are shown, and three replicates had similar results.",
    "ncbi_link": "NTRC: "
  },
  {
    "caption": "(A)  C-circle assay  for tumor samples. The presence of C-circles was tested in 22 osteosarcomas  by Rolling Circle Amplification  (RCA) assay using Φ29 DNA polymerase. Φ29 DNA polymerase  negative controls and Φ29 DNA polymerase-based reactions starting respectively with 75, 37.5, and 18.75 ng of DNA   were applied to dot blots  and C-circles were detected by hybridization  with a 32P-(CCCTAA)4 telomeric  probe. U2OS  and HeLa  cells correspond to positive and negative control samples, respectively.",
    "ncbi_link": "DNA polymerase: 6446511"
  },
  {
    "caption": "(A) Oncoprint graph showing the distribution of mutations  (green rectangles) and copy number variations  (red rectangle, amplification; blue rectangle, copy loss) in all samples. Tumors are distributed according to ALT-positivity (ALT+) or -negativity (ALT-) and ATRX   status (ATRX-mutated or ATRX-wt).",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "(B) Tissue sections of two representative high-grade osteosarcomas  with HES (hematoxylin eosin saffron) staining  (left panel), anti-ATRX  (HPA064684) immunochemistry  (middle panel), and anti-DAXX  (HPA008736) immunochemistry  (right panel), showing ATRX protein expression in two ALT-positive samples. In the top panel, intratumoral ATRX  expression is negative (positive control osteoclasts  are shown). In the bottom panel, intratumoral ATRX  expression is high. Scale bars are 250 μm.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "(A) Copy-number-alteration (CNA) profiles of osteosarcomas. Representation of the GISTIC analysis with false discovery rate (FDR (q-value)) for all cases (n=22; left panel), ALT-positive/ATRX-wt cases (n=11; middle panel), and ALT-positive/ATRX-mutated cases (n=5; right panel).",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "(B) Gain/amplification of TOP3A  gene region (17p11) is a genomic signature of ATRX-wt osteosarcomas. For each ATRX-mutated (top part) and ATRX-wt (bottom part) case, from the left to the right, the chromosome 17 and regional genomic profiles were established, with CGH  Analytics software. A focus was made within the genomic interval (17.25-19.11 Mb) of the short arm of  chromosome 17 (hg38 human genome mapping; Build 38 from NCBI, December 2013 version) including TOP3. Color profiles corresponding to the different tumors are defined at the top of each group. Most ATRX-wt cases show gain or amplification of this region (bottom part), whereas no ATRX-mutated cases display this alteration (top part).",
    "ncbi_link": "ATRX: 546
TOP3: 7156
TOP3A: 7156"
  },
  {
    "caption": "(C) Chromosome 17 copy number variation analysis showing amplification/gain of the TOP3A  region that do not extend into the TP53  gene in ALT ATRX-wt tumors (left panel), and amplification of the TOP3A  region for which TP53  region is at the edge of the amplification/gain in ALT-positive ATRX-wt tumors (right panel).",
    "ncbi_link": "ATRX: 546
TOP3A: 7156
TP53: 7157"
  },
  {
    "caption": "(A) Volcano plot of the supervised analysis of mRNA expression  profiles of osteosarcomas   according to ALT-positive vs. ALT-negative samples, showing upregulated (in red) and downregulated (in green) genes. Twelve tumors had sufficient RNA quality to be analyzed: seven ALT-positive ATRX-wt, two ALT-positive/ATRX-mutated and three ALT-negative.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "(B) TOP3A gene expression  according to ALT  and ATRX  status: ALT+/ATRX-wt (n=7), ALT+/ATRX-mut (n=2) and ALT- (n=3). Box-and-whisker plot were defined with default parameters by median value (central band at the 50th percentile), interquartile ranges (IQR, box limited by 25th and 75th percentile) and whisker boundaries defined by minimum and maximum value. An ANOVA statistical test, and Tukey's range test were used to compare modalities.",
    "ncbi_link": "ATRX: 546
TOP3A: 7156"
  },
  {
    "caption": "(B)  Western blot  showing TOP3A protein expression in nine osteosarcoma  cell lines and NY  siTOP3A as control.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "(D) C-circle assay showing inverse effect of ATRX ectopic expression on  C-circle  levels in ATRX-mutated and ATRX-wt cell lines. Error bars represent the mean ± SEM from n = 2 experiments, n.s. = non-significant, *p < 0.05, Mann-Whitney test.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "(E) C-circle assay showing rescue of ATRX  ectopic expression by TOP3A  overexpression in U2OS osteosarcoma  cells Error bars represent the mean ± SEM from n = 2 experiments, n.s. = non-significant, *p < 0.05, Mann-Whitney test. Western blot and quantification of TOP3A  expression is shown for U2OS  cells overexpressing TOP3A.",
    "ncbi_link": "ATRX: 546
TOP3A: 7156"
  },
  {
    "caption": "(B) Representative images of telomeric  DNA (green) and PML  protein (red) colocalizations  (APBs) in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD. Scale bars are 5 μm. (C) Quantification of APB  frequency in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD; Error bars represent the mean ± SEM from n = 3 experiments, n = 150 cells scored per treatment, n.s., non-significant; Mann-Whitney test. (D) Effect of TOP3A  KD on Telomere  Dysfunction-Induced Foci (TIFs) in osteosarcoma  and in vitro-immortalized cell lines; Error bars represent the mean ± SEM from n = 3 experiments, n = 150 cells scored per treatment, *p < 0.05, **p < 0.005; Mann-Whitney test.",
    "ncbi_link": "ATRX: 546
TOP3A: 7156"
  },
  {
    "caption": "(E) Distributions of TeSLA  fragments in osteosarcoma  and in vitro-immortalized ATRX-mutated or ATRX-wt cell lines according to TOP3A  KD (left panel; each dot represents a TeSLA  fragment), and representative TeSLA Southern Blot image for NY  (right panel).",
    "ncbi_link": "ATRX: 546
TOP3A: 7156"
  },
  {
    "caption": "(A) FISH-IF  of telomeres  (in red) and BLM  (in green) in TOP3A-depleted cells BLM  foci at telomeres  are indicated by white arrows. Error bars represent the mean ± SEM from n = 3 experiments, n = 150 cells scored per treatment, n.s. = non-significant, **p < 0.01, Mann-Whitney test. Scale bars are 5 μm.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "(B) ATSA assay assessing ALT-mediated telomeric DNA synthesis (telomere  in red, EdU  in purple) in PML  (in green) according to TOP3A  KD. EdU  signal at APB  (telomere/PML) are indicated by white arrows. Approximately 150 cells were divided into five groups (0,1-2, 3-4, 5-6n and ≥7) based on the number of EdU+APBs. Scale bars are 5 μm.",
    "ncbi_link": "TOP3A: 7156"
  },
  {
    "caption": "Expression of USP28 (left) and TP63 (right) in human lung squamous cell carcinomas (SCC, n=498), adenocarcinomas (ADC, n=513) and normal non-transformed tissue (normal SCC=338, normal ADC=348). Xena UCSC software. In box plots, the centre line reflects the median, the cross represents the mean and the upper and lower box limits indicates the first and third quartile. Whiskers extend 1.5x the IQR and outliers are marked as dots.",
    "ncbi_link": "TP63: 8626
USP28: 57646"
  },
  {
    "caption": "Correlation of mRNA expression of USP28 and TP63 in lung SCC (left, n=498), ADC (right, n=513) and normal, non-transformed tissue (normal SCC=338, normal ADC=348). R: Spearmans correlation coefficient; m=Slope. Xena UCSC software.",
    "ncbi_link": "TP63: 8626
USP28: 57646"
  },
  {
    "caption": "Kaplan-Meier estimator of NSCLC patients stratified by USP28 (left, n=1145) and TP63 (right, n=1926) expression. p-values were calculated using log-rank test. HR: hazard ratio. Kmplot software.",
    "ncbi_link": "TP63: 8626
USP28: 57646"
  },
  {
    "caption": "Kaplan-Meier estimator of lung SCC patients stratified by USP28 expression (n=271). The p-value was calculated using a logrank test. HR: hazard ratio. Kmplot software.",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "Co-immunoprecipitation of exogenous HA-USP28 and FLAG-ΔNp63 in HEK293 cells. Either HA-USP28 or FLAG-ΔNp63 were precipitated and blotted against FLAG-ΔNp63 or HA-USP28. The input corresponds to 10% of the total protein amount used for the IP (ACTIN as loading control).",
    "ncbi_link": "FLAG: 
HA: 
ΔNp63: 8626
USP28: 57646"
  },
  {
    "caption": "Ni-NTA His-ubiquitin pulldown in control transfected or HA-USP28 overexpressing HEK293 cells, followed by immunoblot against exogenous ΔNp63. The input corresponds to 10% of the total protein amount used for the pull down. Relative ubiquitination of the representative immunoblot was calculated using undefined for normalization.",
    "ncbi_link": "HA: 
USP28: 57646"
  },
  {
    "caption": "Ni-NTA His-ubiquitin pulldown K48 or K63 in control and HA-USP28 overexpressing HEK293 cells, followed by immunoblot against exogenous ΔNp63. The input corresponds to 10% of the total protein amount used for the pulldown. Relative ubiquitination of the representative immunoblot was calculated using VINCULIN for normalization.",
    "ncbi_link": "HA: 
USP28: 57646"
  },
  {
    "caption": "Ni-NTA His-ubiquitin pulldown in control, FLAG-USP28 or FLAG-USP28 C171A transfected HEK293 cells, followed by immunoblot against exogenous ΔNp63. The input corresponds to 10% of the total protein amount used for the pulldown. Relative ubiquitination of the representative immunoblot was calculated using ACTIN for normalization.",
    "ncbi_link": "FLAG: 
USP28: 57646"
  },
  {
    "caption": "CHX chase assay (100ug/ml) of control, FLAG-USP28 or FLAG-USP28 C171A transfected HEK293 cells for indicated time points. Representative immunoblot analysis of FLAG (USP28) and ∆Np63 as well quantification of relative protein abundance (ACTIN as loading control).",
    "ncbi_link": "FLAG: 
USP28: 57646"
  },
  {
    "caption": "Inducible depletion of USP28 in A-431 upon treatment with doxycycline (1µg/ml) for 96h, western blot (left, VINCULIN as loading control) and qPCR analysis of USP28 and ∆Np63 expression relative to ACTIN (right) was performed.",
    "ncbi_link": "ACTIN: 
∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "Tandem ubiquitin binding entity (TUBE) pulldown of endogenous ubiquitylated ∆Np63 in A-431 cells upon DOX depletion of USP28. Relative ubiquitination of the representative immunoblot was calculated using ACTIN for normalization.",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "Cycloheximide (CHX) chase assay (100µg/ml) of control or inducible sh-USP28 A-431 cell line (EtOH or 1µg/ml dox) for indicated time points. Representative immunoblot (left, VINCULIN as loading control) of USP28 and ∆Np63 and quantification of relative protein abundance (right).",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "Doxycycline induced murine USP28 overexpression (EtOH or 1ug/ml dox for 96 hours) in A-431 cells followed by immunoblot (VINCULIN as loading control) and qPCR analysis of USP28 and ∆Np63. For qPCR, human USP28 and murine USP28 (mUSP28) primers were used. Relative mRNA was calculated using ∆∆Ct analysis for human USP28 and ∆Ct for mUSP28 (ACTIN as housekeeping).",
    "ncbi_link": "ACTIN: 
∆Np63: 8626
USP28: 57646
USP28: 235323"
  },
  {
    "caption": "TUBE pulldown of endogenous ubiquitylated ∆Np63 in A-431 cells upon overexpression of mUSP28 for 96 hours (EtOH or 1µg/ml dox). Relative ubiquitination of the representative immunoblot was calculated using ACTIN for normalization.",
    "ncbi_link": "USP28: 235323"
  },
  {
    "caption": "CHX chase assay (100µg/ml) of control or inducible mUSP28 overexpressing A-431 cell line (EtOH or 1µg/ml dox) for indicated time points. Representative immunoblot analysis of USP28 and ∆Np63 as well quantification of relative protein abundance (VINCULIN as loading control).",
    "ncbi_link": "USP28: 235323"
  },
  {
    "caption": "Immunoblot of control (sh-NTC) and two independent shRNA targeting USP28 (sh-USP28#1 and #2) for ∆Np63 and USP28 protein abundance in LUDLU-1adh (VINCULIN as loading control), followed by qPCR analysis of USP28 and ∆Np63 expression relative to ACTIN.",
    "ncbi_link": "ACTIN: 
∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "Doxycycline induced mUSP28 overexpression (EtOH or 1µg/ml dox for 96 hours) in LUDLU-1adh cells followed by immunoblot (VINCULIN as loading control) and qPCR analysis of USP28, mUSP28 and ∆Np63. Relative mRNA was calculated using ∆∆Ct analysis for human USP28 and ∆Ct for mUSP28 (ACTIN as housekeeping for the analysis).",
    "ncbi_link": "ACTIN: 
∆Np63: 8626
USP28: 235323
USP28: 57646"
  },
  {
    "caption": "Correlation of gene expression changes upon constitutive transduction of A-431 cells with either shRNA targeting USP28 (sh-USP28#1) or ∆Np63 (sh-∆Np63#2) relative to non-targeting control (sh-NTC). The diagonal line reflects a regression build on a linear model. R: Pearsons correlation coefficient, m: slope of the linear regression model",
    "ncbi_link": "∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "Gene set enrichment analysis (GSEA) of a gene set of significantly down-regulated genes in sh-∆Np63#2 transfected A-431 cells (\"Down-regulated sh-∆NP63\", Appendix Table S1). The gene set was analysed in sh-∆Np63#2 (left) and sh-USP28#1-depleted (right) A-431 cells. (N)ES: (normalised) enrichment score",
    "ncbi_link": "∆Np63: 8626
∆NP63: 8626
USP28: 57646"
  },
  {
    "caption": "Gene set enrichment analysis (GSEA) of a gene set of significantly down-regulated genes in sh-USP28#1 transfected A-431 cells (\"Down-regulated sh-USP28\", Appendix Table S1). The gene set was analysed in shUSP28#1 (left) and sh-∆Np63#-depleted (right) A-431 cells. (N)ES: (normalised) enrichment score",
    "ncbi_link": "∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "Immunoblot of endogenous ΔNp63 and USP28 in A-431 cells stably transduced with constitutive shRNA-non-targeting control (NTC) or against USP28 and transiently transfected with exogenous ΔNp63. ACTIN served as loading control. Representative western blot from three independent experiments.",
    "ncbi_link": "ΔNp63: 8626
USP28: 57646"
  },
  {
    "caption": "Cell growth of A-431 cells stably transduced with constitutive shRNA-non-targeting control (NTC) or against USP28 and transiently transfected with exogenous ΔNp63. Total cell number was measured and assessed at indicated time points. Quantitative graph is represented as mean ± SD of three experiments (n=3). p-values were calculated using two-tailed t-test statistical analysis. *p-value < 0.05, **p-value < 0.01",
    "ncbi_link": "ΔNp63: 8626
USP28: 57646"
  },
  {
    "caption": "Relative expression of SCC marker genes KRT5, 14 and 19 in A-431 cells stably transduced with constitutive shRNA-non-targeting control (NTC), two independent shRNA-ΔNp63, two independent shRNA-USP28 or ΔNp63 in shRNA-USP28#1, normalised to ACTIN. Quantitative graph is represented as mean ± SD of three experiments (n=3).",
    "ncbi_link": "ACTIN: 
KRT5: 3852
ΔNp63: 8626
USP28: 57646"
  },
  {
    "caption": "Relative expression of epithelial marker genes KRT10 and GPCR5A in A-431 cells stably transduced with constitutive shRNA-non-targeting control (NTC), two independent shRNA-ΔNp63 and shRNA-USP28#1, normalised to ACTIN. Quantitative graph is represented as mean ± SD of three experiments (n=3).",
    "ncbi_link": "ACTIN: 
GPCR5A: 9052
KRT10: 3858
ΔNp63: 8626
USP28: 57646"
  },
  {
    "caption": "Genomic signature of primary human lung SCC samples comprising USP28, ∆Np63, KRT5, KRT14, KRT19, DSG3, MKI67, PCNA and GPRC5A. Samples were sorted dependent on relative USP28 expression (high to low). n=553. Xena UCSC software.",
    "ncbi_link": "DSG3: 1830
GPRC5A: 9052
KRT14: 3861
KRT19: 3880
KRT5: 3852
MKI67: 4288
PCNA: 5111
∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "GSEA of consensus squamous cancer marker genes (se Appendix Table S2) in A-431 cells stably transduced with sh-∆Np63#2 or sh-NTC. (N)ES: (normalised) enrichment score GSEA of consensus squamous cancer marker genes in A-431 cells stably transduced with sh-USP28#1 or sh-NTC. (N)ES: (normalised) enrichment score",
    "ncbi_link": "∆Np63: 8626
USP28: 57646"
  },
  {
    "caption": "Correlation of mRNA expression of consensus squamous cancer marker genes and TP63 in lung SCC and non-transformed lung tissue (Normal). R: Spearmans correlation coefficient. n=836. Gepia software. Correlation of mRNA expression of consensus squamous cancer marker genes and USP28 in lung SCC and non-transformed lung tissue (Normal). R: Spearmans correlation coefficient. N=836. Gepia software.",
    "ncbi_link": "TP63: 8626
USP28: 57646"
  },
  {
    "caption": "Representative qPCR of SCC and ADC marker expression in two independent KP lung tumour clones, resulting in KPADC and KPSCC; (ACTIN served as loading control). Quantitative graph is represented as mean ± SD of three experiments (n=3).",
    "ncbi_link": "ACTIN: "
  },
  {
    "caption": "Representative haematoxylin and eosin (H&E) images of tumour bearing animals 8 weeks post intratracheal transplantation of 2 × 105 cells/animal. KPSCC sh-NTC (n=3); KPSCC sh-USP28 (n=3), Scale bar = 5000µm",
    "ncbi_link": "USP28: 235323"
  },
  {
    "caption": "Quantification of % tumour area (top, normalised to total lung area) and lung tumour numbers (bottom) on KPSCC sh-NTC (n=6) and KPSCC sh-USP28 (n=6) animals.",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "Representative IHC staining for ADC (TTF-1) and SCC (KRT5 and ∆Np63) marker expression as well as Usp28 and GFP abundance in KPSCC sh-NTC (n=3) and KPSCC sh-USP28 (n=3) lung tumours. Scale bar =50 µm",
    "ncbi_link": "USP28: 235323"
  },
  {
    "caption": "Analysis of occurring TP63 genetic alterations in lung squamous (LUSC), cervical (CESC), oesophagus (ESCA), head and neck (HNSC) and pancreatic (PAAD) tumours. Cbioportal.",
    "ncbi_link": "TP63: 8626"
  },
  {
    "caption": "Expression of TP63 (left) and USP28 (right) in human Lung (n=498), Cervix (n=254), Oesophagus (n=96) and HNSC (n=522) SCC tumours and normal non-transformed tissue (nLung=338 nCervix=3, nOesophagus=11 and nHNSC=44). In box plots, the centre line reflects the median, the cross represents the mean and the upper and lower box limits indicates the first and third quartile. Whiskers extend 1.5x the IQR. p-values were calculated using two-tailed t-test statistical analysis. Xena UCSC software.",
    "ncbi_link": "TP63: 8626
USP28: 57646"
  },
  {
    "caption": "Correlation of mRNA expression of KRT14 / KRT7 and TP63 in ADC and SCC tumours for Lung (nADC=513 and nSCC=498), Cervix (nADC=47 and nSCC=254) and Oesophagus (nADC=89 and nSCC=96). Blue dots: ADC; Red dots: SCC; R= Spearmans correlation coefficient; m: Slope. Xena UCSC.",
    "ncbi_link": "KRT14: 3861
KRT7: 3855
TP63: 8626"
  },
  {
    "caption": "Immunoblot of control (sh-NTC) and two independent shRNA targeting USP28 (sh-USP28#1 and #2) for ∆Np63, KRT14 and USP28 protein abundance in H1299, LUDLU-1adh, HELA, SiHa, Ca Ski, PANC-1 and BXPC-3 (ACTIN as loading control).",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "Cells were seeded at equal cell density and counted after five days, Brigth field images of control or sh-USP28#2 infected H1299, LUDLU-1adh, Hela, CaSKI, PANC-1 and BXPC-3 cells before quantification. Scale bar = 30µm Relative number of H1299, LUDLU-1adh, Hela, CaSKI, SiHa, PANC-1 and BXPC-3 sh-USP28#2 cells compared with sh-NTC control cells. p-values were calculated using two-tailed t-test statistical analysis. SiHa* = Notably, the human SCC cell line SiHa was negative for ΔNp63.",
    "ncbi_link": "USP28: 57646"
  },
  {
    "caption": "(D) Control and  EXT1-/- XG1  cells were exposed to SARS-CoV-2  pseudovirus or SARS-CoV-2 pseudovirus pre-treated with 250 IU/mL UF  heparin for 30 min at 37°C. After incubation for 4h at 4°C, cells were lysed and binding  was measured by  ELISA. Data information: Data show the mean values and error bars are the SEM. Statistical analysis was performed using two-way ANOVA with Dunnett's multiple-comparison test. *P≤0.05, **P≤0.01 (n=3).",
    "ncbi_link": "EXT1: 2131"
  },
  {
    "caption": "(A) Namalwa cells ectopically expressing either Syndecan 1 or 4 were exposed to either SARS-CoV-2  pseudovirus alone or SARS-Cov-2  pseudovirus pre-treated with UF heparin  (250 IU/mL) or LMWH enoxaparin (250 IU/mL) for 30 min at 37°C. Binding was measured after 4 hours at 4°C by ELISA. (B) SARS-CoV-2 isolate (hCoV-19/Italy) was pre-incubated with LMWH  enoxaparin (250 IU/mL) for 30 min at 37°C. Namalwa  cells expressing Syndecan 1 and 4 were exposed to either SARS-CoV-2 isolate (100 TCID/mL) or SARS-CoV-2 isolate (100 TCID/mL) pre-treated with LMWH LMWH enoxaparin (250 IU/mL) for 4 hours at 4°C and binding was determined by  quantitative real-time PCR. Data show the mean values and error bars are the SEM. Statistical analysis was performed using (A) 2way-ANOVA with Dunnett's multiple-comparison test. *P≤0.05, **P≤0.01 (n = 7), (B) 2way-ANOVA with Sidak's multiple-comparison test. *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001 (n = 3 measured in triplicate).",
    "ncbi_link": "Syndecan 1: 6382"
  },
  {
    "caption": "(B) SARS-CoV-2 isolate (hCoV-19/Italy) was pre-treated for 30 min at 37°C with either LMWH enoxaparin (250 IU/mL) or one of the following neutralizing antibodies (COVA1-18, 1-21 and 2-15), a non-neutralizing antibody (COVA1-27) or a human IgG1 isotype control, all at the concentration of 1 pg/mL. SARS-CoV-2 isolate alone or with blocks was added at a concentration of 100 TICD/mL. Detection of virus  binding to Syndecan 1 expressing  Namalwa was measured by  quantitative real-time PCR. Data information: Data show the mean values and error bars are the SEM. Statistical analysis was performed using ordinary one-way with Tukey's multiple-comparison test. *P≤0.05, **P≤0.01 (n=2 measured in duplicates).",
    "ncbi_link": "Syndecan 1: 6382"
  },
  {
    "caption": "(B) ACE2, Syndecan 1  and Syndecan 4 cell surface expression on nasal epithelial cells, compared to polarized epithelial Calu-3 was confirmed by quantitative real-time PCR. (C, D) Nasal epithelial cells were exposed to SARS-CoV-2  isolate (hCoV-19/Italy, 100 TCID/mL) either directly or after pre-treatment with antibodies against ACE2 cell surface receptors (1 hour at 37°C )or after pre-treatment with LMWH enoxaparin (250 IU/mL) for 30 min at 37°C. Detection of viral binding  after 4 hours at 4°C (C) and persistently-infected cells lysed after 24 hours at 37°C (D) was determined by quantitative real-time PCR. Data information: Data show the mean values and error bars are the SEM. Statistical analysis was performed using (C, D) ordinary on-way ANOVA with Tukey's multiple-comparison test. *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001 (C) (n=3), (D) (n=3 in duplicates).",
    "ncbi_link": "ACE2: 59272
Syndecan 1: 6382
Syndecan 4: 6385"
  },
  {
    "caption": "B. Bimolecular fluorescence complementation between subunits of the Dsl complex and the COPI coat. The BiFC pair β'-COPVN•Dsl3pVC yielded fluorescent foci that showed dramatically reduced fluorescence intensity in the COPI binding-deficient dsl1-5xWA mutant. Schematic yeast cell representations depict the typical BiFC foci localization patterns. Scale bar 10 μm.",
    "ncbi_link": "dsl1: 855463"
  },
  {
    "caption": "C. Quantification of the β'-COPVN•Dsl3pVC BiFC signals in wild type cells and in COPI binding-deficient dsl1-5xWA and dsl1-Δlasso mutants (as shown exemplarily in (B)). Mean values + SEM of at least three independent experiments (n=3-8) are displayed. Statistical analysis was carried out by comparing the number of cells with BiFC signals over integrated thresholds to those without signals (*=p<0,05). dsl1 mutant strains show a significant decrease in brightness, spot number and spot size in comparison with their corresponding DSL1 wild type strains (two-sample t-test). The dsl1-5xWA mutation also led to comparable signal reduction in cells carrying the VNI152L variant in the β'-COPVN I152L•Dsl3pVC combination.",
    "ncbi_link": "dsl1: 855463
DSL1: 855463"
  },
  {
    "caption": "F. Growth effects of Venus fragment tags in dsl1 mutant cells. Serial tenfold dilutions of liquid cell cultures were spotted on agar plates and incubated at 30 °C for two days. The images in the second row show that β'COPVN producing cells expressing the dsl1-5xWA mutation could not grow. The complementation of β'COPVN by its cognate interaction partners Dsl1pVC and Dsl3pVC, but not by non-cognate BiFC partners (Sec24pVC, Sec16pVC or VCRer1p), suppressed these growth defects. Spot assays of exemplary BiFC partners are depicted. Asterisk: Dsl1pVC carrying the dsl1-5xWA defect was expressed from a plasmid. See Fig EV1, EV2 and Appendix Fig S1 for full data display.",
    "ncbi_link": "dsl1: 855463"
  },
  {
    "caption": "G. BiFC signal quantifications of the strains presented in (F). β'-COPVN yielded BiFC fluorescence signals with all tested complementation partners. This rules out the possibility that the lack of suppression observed in F simply reflects the inability of the BiFC partners to form a complex, and shows that the successful complementation of the split-YFP fragments does not per se suppress the synthetic lethal effect of the VN tag in dsl1-5xWA cells. Mean values + SEM of at least three independent experiments (n=3-8) are displayed.",
    "ncbi_link": "dsl1: 855463"
  },
  {
    "caption": "Time-lapse micrographs of agarose-embedded cells were taken at RT with fresh PM Glc+ura medium supply throughout one budding cycle. Representative images of characteristically reoccurring fluorescence localization stages are displayed. In all combinations, fluorescence foci localize to areas of membrane outgrowth in the bud. Often, another prominent fluorescent spot is found in the mother cell on the side of the bud neck. Scale bar 5 µm. Kymographs of all time-lapse datasets shown in this Figure are presented in Fig EV3A.I. β'-COPmGFPfluorescence foci in Dsl1p-depleted GAL-DSL1 cells after incubation in glucose-containing medium (YEPD) for 4 h at 30 °C.",
    "ncbi_link": "DSL1: 855463"
  },
  {
    "caption": "A. Fluorescence micrographs of two different COPI•COPII BiFC pairs are shown: Sec16pVN•α-COPVC or Sec16pVN•ε-COPVC. DSL1 cells show dispersed punctate patterns resembling ER exit site patterns. In the dsl1-5xWA mutant, cells exhibit additional bright spots. Scale bar 10 µm.B. Quantification of fluorescence intensity differences of the strains shown in (A). COPI•COPII BiFC fluorescence is significantly increased in cells carrying the dsl1-5xWA mutant as compared to DSL1 wild type. Mean values + SEM of at least nine independent experiments (n=918) are displayed (two-sample unpaired twotailed ttest).",
    "ncbi_link": "DSL1: 855463
dsl1: 855463"
  },
  {
    "caption": "C. Time-lapse micrographs of cells expressing the β'-COPVN•Dsl3pVC BiFC pair in a dsl1-5xWA background. Cells were imaged embedded in agarose at RT with fresh PM Glc+ura medium supply throughout one budding cycle. Fluorescence signals retain the characteristic polarization pattern as seen DSL1 wild type cells (see Fig 3). Scale bar 10 μm.",
    "ncbi_link": "dsl1: 855463
DSL1: 855463"
  },
  {
    "caption": "C-E. Involvement of myosin motors in BiFC foci polarization. Time-lapse micrographs of agarose-embedded cells carrying the COPI•Dsl BiFC pairs Dsl1pVN•ε-COPVC or β'COPVN•Dsl3pVC were taken. Either wild type cells (E) or mutants carrying the myosin V mutations myo2-66 (C) or myo4∆ (D) were analyzed. Cells were grown at RT with fresh PM Glc+ura medium supply. In the myo2-66 cells, the BiFC signal polarization was hardly detectable even at permissive temperature, while it was unaffected in myo4∆ compared to the control cells.",
    "ncbi_link": "myo2: 854504
myo4: 851204"
  },
  {
    "caption": "F. Fluorescence micrographs of β'-COPVN•Dsl3pVCcells carrying the myo2-66 defect. COPI•Dsl BiFC, as well as ER or Golgi markers were analyzed. While the BiFC spots were dispersed in these mutants, they retained their association with ER and Golgi. Scale bar 5 μm.",
    "ncbi_link": "myo2: 854504"
  },
  {
    "caption": "A Pancreatic  sections (20X magnification) from 10-months old WT and Glo1KD mice stained  with hematoxylin  and eosin (H&E), anti-insulin, anti-glucagon   and anti-F4/80  antibodies, are representative of sections from 7 mice  each group.",
    "ncbi_link": "Glo1: 109801"
  },
  {
    "caption": " A. RT-PCR of CNPase (left) and MBP (right) mRNAs expression in MO3.13 precursors under control conditions and following 10-200 μM D-Asp exposure for 3 days. Graphs show quantification of ratio of CNPase, and MBP to L19 Data information: The values represent the means ± S.E.M. Level of significance was determined by using: in A, left panel, one-way ANOVA P<0.0001 followed by Tukey's post hoc test, *P< 0.05 versus control (n=3); A, right panel, one-way ANOVA P<0.0001 followed by Tukey's post hoc test, *P<0.05 versus control (n=3 ",
    "ncbi_link": "L19: 
CNPase: 1267
MBP: 4155"
  },
  {
    "caption": " A. RT-PCR of CNPase mRNA expression in oligodendrocyte MO3.13 progenitors under control conditions and following 200 μM D-Asp exposure for 3 days, in absence or in presence of 10 μM MK-801 (left panel), or 30 nM YM-244769 or 100 nM BED (right panel). Graphs show quantification of ratio of CNPase to L19 Data information: The values represent the means ± S.E.M from 3 independent experimental sessions. Level of significance was determined by using: in A, left, one-way ANOVA P=0.009 followed by Tukey's post hoc test, *P< 0.05 versus control, ˄P< 0.05 versus D-Asp (n=3); A, right, one-way ANOVA P=0.0001 followed by Tukey's post hoc test, *P< 0.05 versus control, ˄P< 0.05 versus D-Asp (n=3 ",
    "ncbi_link": "L19: 
CNPase: 1267"
  },
  {
    "caption": " B. RT-PCR of MBP mRNA expression in MO3.13 cells under control conditions and following D-Asp exposure for 3 days, in absence or in presence of 10 μΜ MK-801 (left panel), or 30 nM YM-244769 or 100 nM BED (right panel) Graphs show quantification of ratio of MBP to L19 Data information: The values represent the means ± S.E.M from 3 independent experimental sessions. Level of significance was determined by usin B, left, one-way ANOVA P=0.0001 followed by Tukey's post hoc test, *P< 0.05 versus control, ˄P< 0.05 versus D-Asp (n=3); B, right, one-way ANOVA P=0.0004 followed by Tukey's post hoc test, *P< 0.05 versus control, ˄P< 0.05 versus D-Asp (n=3",
    "ncbi_link": "L19: 
MBP: 4155"
  },
  {
    "caption": " D. RT-PCR of NCX3 mRNA expression under control conditions and following 10-200 μM D-Asp exposure or 100 nM PMA for 3 days Data information: The values represent the means ± S.E.M from 3 independent experimental sessions. Level of significance was determined by using: i D, one-way ANOVA P=0.0001 followed by Tukey's post hoc test, *P< 0.05 versus control, ˄P< 0.05 versus D-Asp (n=3)",
    "ncbi_link": "NCX3: 6547"
  },
  {
    "caption": " E. RT-PCR of NCX3 mRNA expression following 200 μM D-Asp exposure, in absence or in presence of 10 μM MK-801 Data information: The values represent the means ± S.E.M from 3 independent experimental sessions. Level of significance was determined by using E, one-way ANOVA P=0.0083 followed by Tukey's post hoc test, *P<0.05 versus control, ˄P< 0.05 versus D-Asp (n=3), n.s, not significant",
    "ncbi_link": "NCX3: 6547"
  },
  {
    "caption": " F. RT-PCR of NCX1 mRNA expression following 200 μM D-Asp exposure, in absence or in presence of 10 μM MK-801. Graphs show quantification of ratio of NCX1 and NCX3 to L19 ",
    "ncbi_link": "L19: 
NCX1: 6546
NCX3: 6547"
  },
  {
    "caption": " E. left panel; Superimposed single-cell traces representative of the effect of 100 μM D-Asp on [Ca2+]i detected in MO3.13 cells in presence of siCtl or sincx3 silencing. E, right panel; Quantification of the oscillation index in MO3.13 cells in absence or in presence of sincx3. e, Quantification of the initial [Ca2+]i increase elicited by D-Asp and measured as ∆% of peak versus basal values in absence or in presence of sincx3 Data information: The values represent the mean ± S.E.M from 3 independent experimental sessions. Level of significance was determined by usin E and e, one way-ANOVA P<0.001 followed by Bonferroni post hoc test, *P< 0.05 versus sictl, ˄P< 0.05 versus D-Asp + sictl. Data are reported as mean of 25-30 cells in each group, n=3 biological replicate",
    "ncbi_link": "ncx3: 6547"
  },
  {
    "caption": " F. left panel. Superimposed single-cell traces representative of the effect of 100 μM D-Asp on [Ca2+]i detected in primary OPC obtained from wild-type ncx3+/+, heterozygous ncx3 +/-, and knock-out ncx3-/- mice. F. right panel. Quantification of the oscillation index elicited by D-Asp in primary mouse OPC obtained from ncx3+/+, ncx3 +/-, and ncx3-/- mice. f, Quantification of the initial [Ca2+]i increase measured as ∆% of peak versus basal values Data information: The values represent the mean ± S.E.M from 3 independent experimental sessions. Level of significance was determined by using F and f, one way-ANOVA P<0.001 and P=0.003, respectively, followed by Bonferroni post hoc test, *P< 0.05 versus basal value, ˄P< 0.05 versus ncx3+/+ and ncx3+/-. Data are reported as mean of 10-19 cells in each group, n=3 biological replicates",
    "ncbi_link": "ncx3: 140448"
  },
  {
    "caption": "(b) Experimental values for the EVL advancing front speeds at different epiboly stages (φ angle - top) and at different times (bottom) for wild type controls (blue) and Msn1yolk morphants with reduced E-YSL contractility (red). Experimental profiles closely approach to those inferred in the simulations (compare to (a)).",
    "ncbi_link": "Msn1: 286739"
  },
  {
    "caption": "(c) Timeline showing medial sections and power isolines for wild type (top) and Msn1yolk morphants (bottom) along epiboly. Mechanical parameters were inferred by HR from experimental velocity fields (Movie EV10). The RMSE of power is shown as a percentage at each time point. DCs in the Msn1yolk morphants undergo ingression on schedule at 50 % epiboly (yellow arrow). Importantly, as in wild type controls, the active work in morphants is detected at the E-YSL (red arrow). This power supply fades away as epiboly slows down and eventually fails. Scale bar 100 μm.",
    "ncbi_link": "Msn1: 286739"
  },
  {
    "caption": "(d) Tensional profiles normalized values in arbitrary units inferred by HR for wild type at 80 % epiboly and its temporal equivalent (9 hours after egg laying) for Msn1yolk morphants. The characteristic profiles of longitudinal and latitudinal stresses and the animal to vegetal stress gradient that are built up during epiboly are never properly developed in morphants.",
    "ncbi_link": "Msn1: 286739"
  },
  {
    "caption": "B (left) Immunoblotting of LDHA in melanoma cell lines transfected with non-targeting siRNA (NT-siRNA) or LDHA-specific siRNA for 72 hr. (right) Proliferation of melanoma cell lines transfected with NT-siRNA or LDHA-specific siRNA for the indicated timepoints. Data information: Statistical analysis was performed by two-way Anova for time-dependent proliferation changes and by one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. In (B), statistical comparison for the treatments that showed a significant change.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "Immunoblotting of LDHA of MeWo and A375 cells stably transduced with empty vector (EV) or LDHA-specific shRNAs.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "proliferation under normoxic (D) conditions of MeWo and A375 cells stably transduced with empty vector (EV) or LDHA-specific shRNAs. Data information: Statistical analysis was performed by two-way Anova for time-dependent proliferation changes and by one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "proliferation under hypoxic conditions of MeWo and A375 cells stably transduced with empty vector (EV) or LDHA-specific shRNAs. Data information: Statistical analysis was performed by two-way Anova for time-dependent proliferation changes and by one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. statistical significance is denoted by blue (for si/sh-LDHA#1, hypoxia) and black (for sish-LDHA#2, hypoxia) stars respectively.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "G Anchorage-independent growth of MeWo and A375 cells stably transduced with empty vector (EV) or LDHA-specific shRNAs. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "D Medium Gln levels after transfection of melanoma cells with non-targeting (NT) or LDHA-specific siRNA for 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "H Immunoblotting of LDHA and SLC1A5 in melanoma cell lines transfected with NT-siRNA or indicated si-LDHA for 96 hr.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "I Immunoblotting of SLC1A5 and LDHA in MeWo cells stably transduced with empty vector (EV) or four different LDHA-­specific shRNAs.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "J Immunoblotting of SLC1A5 in MeWo cells mock (NT-siRNA + DMSO) or si-SLC1A5-treated for 24 hr and then treated with LDHAi for 48 hr.",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "L Proliferation of melanoma cell lines for the indicated timepoints following treatment with LDHA-i, si-SLC1A5 or both. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. two-way Anova was used for the proliferation. N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "N Immunoblotting of SLC1A5 and cleaved caspase-3 in melanoma cells subjected to mock (NT-siRNA + DMSO) or si-SLC1A5 treatment for 24 hr followed by exposure to LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, N.D., not determined. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "B GC-MS-based quantification of intracellular essential amino acid levels in MeWo cells mock or si-SLC1A5-transfected for 24 hr and then treated with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "C (left) Immunoblotting of SLC7A5 in MeWo cells transfected with non-targeting (NT) or SLC7A5-specific siRNAs for 48 hr. (right) GC-MS-based quantification of intracellular essential amino acid levels in MeWo cells mock or si-SLC7A5-transfected for 24 hr and then treated with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "SLC7A5: 8140"
  },
  {
    "caption": "Immunoblotting of total and phosphorylated S6, ULK1, and eIF4EBP1 in melanoma cells (E) transfected with non-targeting (NT) or LDHA-specific siRNAs for 96 hr Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "Immunoblotting of total and phosphorylated S6, ULK1, and eIF4EBP1 in melanoma cells (F) si-SLC1A5-transfected for 24 hr followed by treatment with LDHAi for 72 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "Immunoblotting of ATF4 in melanoma cell lines (B) transfected with non-targeting (NT) or LDHA-specific siRNAs for 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "C Immunoblotting of ATF4 in MeWo cells stably transduced with empty vector (EV) or indicated sh-LDHAs. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "E Immunoblotting of ATF4 and SLC1A5 in melanoma cell lines mock- or si-ATF4-treated for 24 hr and then incubated with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "F qRT-PCR analysis of SLC1A5 transcript levels in melanoma cell lines transfected with si-ATF4 for 24 hr and then incubated with LDHAi for 24 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "ATF4: 468
SLC1A5: 6510"
  },
  {
    "caption": "H Proliferation of melanoma cell lines mock- or si-ATF4-transfected and incubated with LDHAi as indicated for up to 96 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, and two-way Anova was used for the proliferation. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "qRT-PCR analysis of asparagine synthetase (ASNS) and glutamine-pyruvate transaminase 2 (GPT2) mRNA levels in the indicated cell lines after 24 hr treatment with LDHAi. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "ASNS: 440
asparagine synthetase: 440
GPT2: 84706
glutamine-pyruvate transaminase 2: 84706"
  },
  {
    "caption": "GC-MS-based quantification of intracellular Asn and Ala levels in MeWo cells mock-transfected or transfected with si-ATF4 (K) for 24 hr and then treated with LDHAi for 48 hr. and shared Mock and LDHA-i controls. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "ATF4: 468"
  },
  {
    "caption": "GC-MS-based quantification of intracellular Asn and Ala levels in MeWo cells mock-transfected or si-SLC1A5 (L) for 24 hr and then treated with LDHAi for 48 hr. and shared Mock and LDHA-i controls. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "SLC1A5: 6510"
  },
  {
    "caption": "M (left) Immunoblotting of ASNS in MeWo cells mock- or si-ASNS-transfected for 24 hr and then incubated with LDHAi for 48 hr. (right) Proliferation of MeWo cells mock- or si-ASNS-transfected for 24 hr and then incubated with LDHAi for the indicated times. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Unpaired t-test was used for the comparison of two groups, and two-way Anova was used for the proliferation. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "ASNS: 440"
  },
  {
    "caption": "N Immunoblotting of GCN2, ATF4 and SLC1A5 in MeWo cells mock- or si-GCN2-treated for 24 hr and then incubated with LDHAi for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups.",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "O 3H-Glutamine uptake in MeWo cells transfected with si-GCN2 and treated 48 hr later with LDHAi for 6 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "P Gln levels in the medium after treatment of MeWo cells with mock- or si-GCN2 for 24 hr and subsequent incubation with LDHA-i for 48 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "GCN2: 440275"
  },
  {
    "caption": "G GC-MS-based quantification of intracellular Ala (left) and Asp (right) levels in si-GPT2-treated MeWo cells incubated with LDHAi for 1 hr. Data information: Statistical analysis was performed by ordinary one-way Anova for the comparison of more than two groups and unpaired t-test for the comparison of two groups. Data are shown as the mean ± SD, n = 3. ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001",
    "ncbi_link": "GPT2: 84706"
  },
  {
    "caption": "A (left) Immunoblotting of LDHA and ATF4 in A375 cells expressing inducible (Tet-On) sh-LDHA expression vector treated with doxycycline (Dox) for 48 hr. (right) qRT-PCR (n=3) analysis of the ATF4 target genes in A375 cells treated with doxycycline (0.5 μg/ml) for 24 hr. Statistical analysis was performed by unpaired t-test. Data are shown as the mean ± SEM , ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "ATF4: 468
LDHA: 3939"
  },
  {
    "caption": "B Proliferation of inducible (Tet-On) sh-LDHA expression vector harboring A375 cells (n=3) treated with Dox (0.5 μg",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "C Athymic nude mice were injected subcutaneously with A375 melanoma cells expressing inducible (Tet-On) sh-LDHA expression vector. Starting day 5, animals were treated on alternate days with 1 g/L doxycycline, 4 mg/kg rapamycin, or with a combination of the two (n=8 in each group). The tumor growth was determined by measuring the tumor volume. Statistical analysis was performed using Welch's t-test (two-tailed). Data are shown as the mean ± SEM ns: not significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "G Relative mTORC1 expression in pan-tumor samples segregated based on high (LDHAhi) (n=2917) and low LDHA (LDHAlo) (n=2914) expression. The p-value of paired Wilcoxon test following the adjustment multiple hypothesis correction (FDR). Data information: In the boxplots, the top and bottom horizontal lines represent the 75th and the 25th percentile respectively, and the middle horizontal line represents the median. The size of the box represents the interquartile range and the top and bottom whiskers represent the maximum and the minimum values respectively.",
    "ncbi_link": "LDHA: 16828"
  },
  {
    "caption": "H Conditional essentiality of the indicated genes in LDHAlo and LDHAhi cell lines (n=17, each group). The p-value of paired Wilcoxon test following the adjustment multiple hypothesis correction (FDR). p≤0.1 is significant. Data information: In the boxplots, the top and bottom horizontal lines represent the 75th and the 25th percentile respectively, and the middle horizontal line represents the median. The size of the box represents the interquartile range and the top and bottom whiskers represent the maximum and the minimum values respectively.",
    "ncbi_link": "LDHA: 16828"
  },
  {
    "caption": "A qRT-PCR analysis of LDHA mRNA levels in A375 cells treated with BRAF inhibitor (PLX-4032, 1 μM) for 24 hr. Data information: Statistical analysis was performed by unpaired t-test for the comparison of two groups. Data are shown as mean ± SD, n = 3. ns: not significant, **p ≤ 0.01, ****p ≤ 0.0001.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "E, F Heatmap for expression fold-change of ASNS, GPT2, PSAT1, and MITF between (E) post-treatment (BRAF inhibitor, BRAF-i; MEK inhibitor, MEK-i) and pre-treatment, or (F) post-treatment (BRAF-i) and pre-treatment tumor in each of the patients (y-axis). The p-value of paired Wilcoxon test following the adjustment multiple hypothesis correction (FDR) are also displayed; post-treatment expression significantly greater than pre-treatment except in the case of MITF, where post-treatment expression is significantly less than pre-treatment.",
    "ncbi_link": "ASNS: 440
GPT2: 84706
MITF: 4286
PSAT1: 29968"
  },
  {
    "caption": "A Transmigration of mouse neutrophils towards the chemokine CXCL-1 through TNF-α-stimulated VE-cadherin WT (WT) or VE-cadherin Y731F (Y731F) primary endothelial cells, each transfected with control or SHP2-specific siRNA. The transmigration rate is presented relative to that of WT cells transfected with control siRNA, set as 100%. On the right, Western blot analysis of lysates from cells used in transmigration assays for the expression of SHP2 and α-tubulin.",
    "ncbi_link": "VE-cadherin: 12562
SHP2: 19247"
  },
  {
    "caption": "B Transmigration of human neutrophils towards the chemokine IL-8 through TNFα-stimulated human endothelial cells (HUVEC), transfected with control or SHP2-specific siRNA and were either not transduced (-) or transduced (+) with adenoviruses expressing human SHP2 (Adv-SHP2). The transmigration rate is presented relative to that of cells transfected with control siRNA, set as 100%. On the right, Western blot analysis of lysates from cells used in transmigration assays for the expression of SHP2 and α-tubulin.",
    "ncbi_link": "SHP2: 5781"
  },
  {
    "caption": "endothelial cells were stimulated with TNF-α for 17 h prior to adding leukocytes for indicated time points followed by immunoprecipitations and immunoblots of precipitates and endothelial cell lysates (Iso = isotype control). (B) luEnd cells devoid of PECAM-1 (KO) or re-transfected with PECAM-1 (RT) were incubated with T cells for 30 min.",
    "ncbi_link": "PECAM-1: 18613"
  },
  {
    "caption": "endothelial cells were stimulated with TNF-α for 17 h prior to adding leukocytes for indicated time points followed by immunoprecipitations and immunoblots of precipitates and endothelial cell lysates (Iso = isotype control). (C) HUVEC transfected with control or PECAM-1-specific siRNA were incubated with differentiated HL60 cells for 20 min.",
    "ncbi_link": "PECAM-1: 5175"
  },
  {
    "caption": "endothelial cells were stimulated with TNF-α for 17 h prior to adding leukocytes for indicated time points followed by immunoprecipitations above) and immunoblots of precipitates and endothelial cell lysates (Iso = isotype control). (E) HUVEC, siRNA depleted for endogenous PECAM-1, were transduced with wild-type PECAM-1 (PECAM-1 WT) or Y663,686F PECAM-1 double mutant (PECAM-1 YF) and incubated with HL60-derived neutrophils for 20 min. On the right, immunoblot analysis of lysates from siRNA treated cells before PECAM-1 re-expression.",
    "ncbi_link": "PECAM-1: 5175"
  },
  {
    "caption": "F Transmigration of human neutrophils towards IL-8 through TNFα-stimulated HUVEC expressing PECAM-1 WT or PECAM-1-Y663,686F. The transmigration rate is presented relative to that of PECAM-1 WT expressing cells, set as 100%.",
    "ncbi_link": "PECAM-1: 5175"
  },
  {
    "caption": "Endocytosis of VE-cadherin in 17 h TNF-α treated HUVEC was induced by adding HL60-derived neutrophils for 20-30 min at 37°C and monitored by the internalization of preincubated mAb BV6, which was visualized in fixed cells with a secondary fluorescent antibody (white). Total VE-cadherin was stained with another mAb (red), nuclei stained with Hoechst (white). (A) HUVEC had been transfected prior to the experiment with control or PECAM-1-specific siRNA. Cell lysates were analyzed for expression levels of PECAM-1 and tubulin (below). Relative VE-cadherin internalization efficiency is given on the right.",
    "ncbi_link": "PECAM-1: 5175"
  },
  {
    "caption": "Endocytosis of VE-cadherin in 17 h TNF-α treated HUVEC was induced by adding HL60-derived neutrophils for 20-30 min at 37°C and monitored by the internalization of preincubated mAb BV6, which was visualized in fixed cells with a secondary fluorescent antibody (white). Total VE-cadherin was stained with another mAb (red), nuclei stained with Hoechst (white). (B) PECAM-1 siRNA treated HUVEC were transduced with WT PECAM-1-EGFP or PECAM-1-Y663,686F-EGFP. Expression levels of transduced PECAM-1 forms and of EGFP and VE-cadherin are shown in immunoblots (on the right). Relative VE-cadherin internalization efficiency is given on the right.",
    "ncbi_link": "EGFP: 
PECAM-1: 5175"
  },
  {
    "caption": "A Transmigration of mouse neutrophils towards CXCL-1 through TNF-α-stimulated bEnd.5 cells transfected with control or SHP2-specific siRNA and pre-treated with anti-endomucin (7C7.1) or anti-PECAM-1 (Mec13.3) antibodies for 30 min at 37°C before addition of neutrophils. The transmigration rate is presented relative to that of control cells, set as 100%.",
    "ncbi_link": "SHP2: 19247"
  },
  {
    "caption": "Extravasated leukocytes (C) in cremaster tissue from WT or Y731F VE-cadherin mice stimulated intrascrotally with IL-1β and treated i.v. with isotype-control or anti-PECAM-1 (2H8) antibodies for 4 h before intravital microscopy.",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "adherent leukocytes (D) in cremaster tissue from WT or Y731F VE-cadherin mice stimulated intrascrotally with IL-1β and treated i.v. with isotype-control or anti-PECAM-1 (2H8) antibodies for 4 h before intravital microscopy.",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "(D) and rolling flux fraction of leukocytes (E) in cremaster tissue from WT or Y731F VE-cadherin mice stimulated intrascrotally with IL-1β and treated i.v. with isotype-control or anti-PECAM-1 (2H8) antibodies for 4 h before intravital microscopy.",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "A HUVEC were transduced with increasing titers of adenovirus expressing human SHP2. VE-cadherin was immunoprecipitated from cell lysates and precipitates as well as total cell lysates were analyzed by immunoblots for indicated antigens.",
    "ncbi_link": "SHP2: 5781"
  },
  {
    "caption": "A Transmigration of mouse neutrophils towards the chemokine CXCL-1 through TNFα-stimulated WT or Y731F primary endothelial cells, either pre-treated with vehicle control (DMSO) or Ca2+ chelator (MAPTAM) for 30 min at 37°C prior to addition of neutrophils. The transmigration rate is presented relative to DMSO-treated endothelial cells expressing WT VE-cadherin.",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "A Transmigration of mouse neutrophils towards the chemokine CXCL-1 through TNFα-stimulated WT or Y731F primary endothelial cells, either pre-treated with vehicle control (DMSO) or Ca2+ chelator for 30 min at 37°C prior to addition of neutrophils. The transmigration rate is presented relative to DMSO-treated endothelial cells expressing WT VE-cadherin. C Transmigration assays treatment with Blebbistatin.",
    "ncbi_link": "VE-cadherin: 12562"
  },
  {
    "caption": "E HUVEC transduced with lacZ or with SHP2 were either untreated (-) or treated (+) with thrombin for 30 min followed by immunoblotting either VE-cadherin immunoprecipitates or cell lysates for the indicated antigens on the right.",
    "ncbi_link": "lacZ: 
SHP2: 5781"
  },
  {
    "caption": "HUVEC were transfected with control or VE-cadherin-specific siRNA and transduced with VE-cad FL or VE-cad FL-TS. Cell lysates were immunoblotted for VE-cadherin and actin.",
    "ncbi_link": "VE-cad: 1003
VE-cadherin: 1003"
  },
  {
    "caption": "C Immunofluorescence staining for VE-cadherin of HUVEC transfected with control or VE‑cadherin specific siRNA (VE-cad kd) and transduced with VE-cad FL or VE-cad FL-TS. D HUVEC were either transfected with control or VE-cadherin targeting siRNA and transduced with VE‑cad FL or VE-cad FL‑TS. The tension sensor was immunoprecipitated from cell lysates using an anti-GFP antibody. Precipitates as well as total cell lysates were analyzed by immunoblotting for indicated antigens. Molecular weight markers are indicated in kDa. E, Quantification of FRET efficiency (percentage) in junctions of HUVEC expressing VE-cad FL or VE-cad FL-TS, after thrombin stimulation (1 U/ml) or under control conditions. ",
    "ncbi_link": "VE-cad: 1003
VE-cadherin: 1003
VE‑cad: 1003
VE‑cadherin: 1003"
  },
  {
    "caption": "A-C Quantification of FRET efficiency (percentage) in junctions of HUVEC expressing VE-cad FL (A, B) or VE-cad FL-TS (C). HUVEC were stimulated 4h with TNFα prior to adding IL-8 for 4 min, followed by flow with buffer alone (A) or together with PMNs (B, C). The connected data points represent FRET efficiency of same junctions compared before and after addition of flow/PMNs.",
    "ncbi_link": "VE-cad: 1003"
  },
  {
    "caption": "D Quantification of FRET efficiency (percentage) in junctions of HUVEC expressing VE-cad FL or VE-cad FL-TS. Cells were either exposed to flow and PMNs or to flow alone, fixed using 4 % PFA and washed with PBS. FLIM measurements were performed at sites of transmigration (PMNs) or at junctions without PMNs (Flow).",
    "ncbi_link": "VE-cad: 1003"
  },
  {
    "caption": "Three sex chromosome axes could be detected in the 2-month-old XUsp26+XUsp26-Y spermatocytes. Immunofluorescence analysis of SYCP3 (red) and SYCP1 (green) in (J), ATR (red) and SYCP3 (green) in (K) was performed in 2-month-old WT and XUsp26+XUsp26-Y spermatocytes. Nuclei were stained with DAPI (blue).The arrows indicate the Y chromosome. The arrowheads indicate the X chromosome.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "D Histological analysis of the seminiferous tubules and caudal epididymis of the 6-month-old Usp26+/Y and Usp26-/Y mice.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "F The deletion of Usp26 causes pachytene and meiotic division arrest. Representative PAS-hematoxylin staining in 6-month-old Usp26+/Y and Usp26-/Y seminiferous tubules. Paraffin sections from Usp26+/Y and Usp26-/Y testes were stained with PAS-hematoxylin. P: pachytene spermatocyte, D: diplotene spermatocyte, rST: round spermatid, eST: elongating spermatid, M: meiotic spermatocyte, aP: apoptotic pachytene spermatocytes, aM: abnormal meiotic divisions.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "E The X and Y chromosomes were unpaired in Usp26-/Y spermatocytes. Immunofluorescence analysis of Chr X-FISH (green), Chr Y-FISH (red), and SYCP3 (white) was performed in 6-month-old Usp26+/Y and Usp26-/Y spermatocytes. The arrowheads indicate the X chromosome. F Quantification of unpaired X and Y chromosomes in 6-month-old Usp26+/Y and Usp26-/Y mice (n= 5 independent experiments). Red dots indicate Usp26+/Y mice and green dots indicate Usp26-/Y mice.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "Sex chromosome recombination was perturbed in 6-month-old Usp26-/Y mice. Immunofluorescence analysis of SYCP3 (green), MRE11 (red) (G); was performed in 6-month-old Usp26+/Y and Usp26-/Y spermatocytes. Nuclei were stained with DAPI (blue). The arrows indicate the sex chromosomes.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "Sex chromosome recombination was perturbed in 6-month-old Usp26-/Y mice. Immunofluorescence analysis of ; SYCP3 (green), γH2AX (red) (H); SYCP3 (green), ATR (red), p-ATM (pink) (I) was performed in 6-month-old Usp26+/Y and Usp26-/Y spermatocytes. Nuclei were stained with DAPI (blue). The arrows indicate the sex chromosomes.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "L Crossover on sex chromosomes was impaired in 6-month-old Usp26-/Y mice. Immunofluorescence analysis of SYCP3 (green), MLH1 (red), and ATR (white) was performed in 6-month-old Usp26+/Y and Usp26-/Y spermatocytes. Nuclei were stained with DAPI (blue).",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "D Representative TUNEL results in Usp26+/Y and Usp26-/Y testes. Paraffin sections from 6-month-old Usp26+/Y and Usp26-/Y testes were stained with TUNEL (green) and DAPI (blue) to show dead cells in stage IV, VIII and XII tubules with pachytene and metaphase spermatocytes, respectively. The arrowheads indicate the laggard chromosomes. P: pachytene spermatocytes, rSt: round spermatid, spz: spermatozoa, M: meiotic spermatocyte, aP: apoptotic pachytene spermatocytes, aM: abnormal meiotic divisions, arSt: apoptotic round spermatid.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "E The protein level of three known SAC proteins was reduced in 2-month-old and 6-month-old Usp26−/Y mouse testes. Immunoblotting of MAD2, BUBR1, PLK1 and USP26 was performed in 2-month-old and 6-month-old Usp26+/Y and Usp26-/Y testes. H3Ser10p and Tub served as loading control.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "F Usp26-deficient mice produced XY aneuploid round spermatids. FISH analysis of Chr X (green) and Chr Y (red) was performed in 2-month-old and 6-month-old Usp26+/Y and Usp26−/Y round spermatids. Nuclei were stained with DAPI (blue). The arrows indicate the Y chromosome, and the arrowheads indicate the X chromosome. G Quantification of different types of round spermatids in 2-month-old Usp26 +/Y, Usp26-/Y mice (n= 3 independent experiments) and 6-month-old Usp26+/Y (n= 3 independent experiments), Usp26-/Y mice (n= 4 independent experiments). P=0.0026 for XY spermatozoa in 6-month-old Usp26+/Y and Usp26−/Y mice. P=0.0216 for O spermatozoa in 6-month-old Usp26+/Y and Usp26−/Y mice. H Usp26-deficient mice produced XY aneuploid spermatozoa. FISH assay of Chr X (green) and Chr Y (red) was performed in 2-month-old and 6-month-old Usp26+/Y and Usp26−/Y spermatozoa. Nuclei were stained with DAPI (blue). The arrows indicate the Y chromosome, and the arrowheads indicate the X chromosome. I Quantification of different types of spermatozoa in 2-month-old Usp26+/Y, Usp26-/Y mice (n= 3 independent experiments) and 6-month-old Usp26+/Y, Usp26-/Y mice (n= 5 independent ex experiments). P=0.0195 for XY spermatozoa in 6-month-old Usp26+/Y and Usp26−/Y mice. Data are presented as means ± SD.",
    "ncbi_link": "Usp26: 83563"
  },
  {
    "caption": "The X and Y chromosomes were unpaired in Tex11-/Y spermatocytes. Immunofluorescence analysis of SYCP3 (green), TRF1 (red), ATR (white) (D); SYCP3 (green), MLH1 (red), ATR (white) (E) was performed in in Tex11+/Y and Tex11-/Y spermatocytes. Nuclei were stained with DAPI (blue). The arrowheads indicate the X chromosome.",
    "ncbi_link": "Tex11: 83558"
  },
  {
    "caption": "A, B Quantification of different types of spermatozoa in fertile men with or without USP26 mutations. The spermatozoa from fertile men without USP26 mutations (n = 10 independent experiments); fertile men contained the USP26 c.463C>T mutation (The sample was analyzed in three repeated experiments), the USP26 c.125T>C mutation (n = 2 independent experiments, one sample was analyzed in two repeated experiments), the USP26 c.1044T>A mutation (n = 5 independent experiments), and the USP26 c.370_371insACA/494T>C/1423C>T mutation (n = 10 independent experiments) were collected to perform Chr X and Chr Y FISH. P-values are shown for comparison to fertile men without USP26 mutations.",
    "ncbi_link": "USP26: 83844"
  },
  {
    "caption": "C The fertile men with the USP26 mutated haplotype produced XY and O aneuploid spermatozoa. FISH assay of Chr X (green) and Chr Y (red) was performed in fertile men with or without the USP26 mutated haplotype. Nuclei were stained with DAPI (blue). The arrows indicate the Y chromosome, and the arrowheads indicate the X chromosome.",
    "ncbi_link": "USP26: 83844
USP26: 83563"
  },
  {
    "caption": "(B) Histogram displaying the SILAC ratios (log2) of stress-induced phosphorylation sites in setup cdc55Δ (upper panel) and setup rts1Δ (lower panel) (Hollenstein et al., 2020), stratified by their Hog1-dependence (grey area versus thick black line).",
    "ncbi_link": "cdc55: 852685
Hog1: 850803
rts1: 854179"
  },
  {
    "caption": "(D) Transcriptional analysis of stress-induced expression of ESR genes CTT1 (upper panel) and PGM2 (lower panel) under different strain conditions (i.e. presence/absence of IGO1/2 and induction of iAID-Cdc55 depletion). Measured time points after stress application are depicted on the x-axis, target gene mRNA levels are illustrated on the y-axis as fold over reference gene IPP1, values are normalized relative to wild type without induction of iAID-Cdc55 depletion at 30 minutes post-stress.",
    "ncbi_link": "Cdc55: 852685
CTT1: 852979
IGO1: 855565
IPP1: 852296
PGM2: 855131"
  },
  {
    "caption": "E) Transcriptional analysis of stress-induced expression of ESR genes CTT1 (upper panel) and PGM2 (lower panel) at 30 minutes post-stress. Target gene mRNA levels are illustrated on the y-axis as fold over reference gene IPP1, values are normalized relative to wild type without induction of iAID-Cdc55 depletion. dep.: Cdc55 depleted, n.d.: Cdc55 non-depleted.",
    "ncbi_link": "Cdc55: 852685
CTT1: 852979
IPP1: 852296
PGM2: 855131"
  },
  {
    "caption": "(C) Mobility shift assays monitoring phosphorylation-induced mobility changes of Gis1 (two upper rows) and Rph1 (two lower rows) upon hyperosmotic stress in wild type, igo1∆igo2∆ and Cdc55-depleted cells (right-hand side).",
    "ncbi_link": "Cdc55: 852685
igo1: 855565
igo2: 856534"
  },
  {
    "caption": "(E) Western blot phosphorylation shift assays of wild type Gis1-myc (upper panel) and Rph1-Flag (lower panel), and mutated forms Gis1-5A-myc (upper panel) and Rph1-5A-Flag (lower panel). The measurement was done using Phos-tag (Kinoshita et al., 2006) and at the indicated time points after exposure to hyperosmotic stress (0.5 M NaCl) using Pgk1 protein levels as a negative control. The location of the mutated residues is shown in the respective schematics. Red boxes: demethylase associated domains (JmjN and JmjC), blue box: zinc finger domain.",
    "ncbi_link": "Flag: 
myc: 
Gis1: 851670
Rph1: 856916"
  },
  {
    "caption": "(F) Transcriptional analysis of stress-induced expression of ESR genes CTT1 (upper panel) and PGM2 (lower panel) at 30 minutes post-stress across indicated strains expressing either wild type or point-mutated forms of Gis1 and Rph1 in a gis1∆rph1∆ deletion background, with the empty vector as control.",
    "ncbi_link": "CTT1: 852979
gis1: 851670
Gis1: 851670
PGM2: 855131
rph1: 856916
Rph1: 856916"
  },
  {
    "caption": "A Representative images of eyes and lenses from 6-7 week old wildtype (WT) and nervous system-specific YME1L knockout (NYKO) mice. Orange dashed lines mark eye morphology. Scale bars 5 mm.",
    "ncbi_link": "YME1L: 27377"
  },
  {
    "caption": "E mRNA levels of proinflammatory cytokines and NF-κB target genes from 6-7 week old retinas (WT, n = 5; NYKO, n = 5). Transcript levels were normalized to Hprt mRNA levels. Data were analyzed using unpaired t-test, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "Hprt: 15452"
  },
  {
    "caption": "mRNA levels of Fgf21 from 6-7 week old retinas (WT, n = 5; NYKO, n = 5). Transcript levels were normalized to Hprt mRNA levels. Data were analyzed using unpaired t-test, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "Fgf21: 56636
Hprt: 15452"
  },
  {
    "caption": "E mRNA levels of proinflammatory cytokines from spinal cords of 31-32 week old mice (WT, n = 5; NYKO, n = 5). Transcript levels were normalized to Hprt mRNA levels. Unpaired t-test, *P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001, ns = not significant. Data are means ± SEM.",
    "ncbi_link": "Hprt: 15452"
  },
  {
    "caption": "Fluorescence images of isolated cortical neurons from Yme1lfl/fl animals expressing CAG-GFP (WT) or CAG-Cre-IRES-GFP (Yme1l-/-) at DIV12 and stained with TOMM20 to visualize mitochondria. Scale bars 30 µm.",
    "ncbi_link": "Yme1l: 27377"
  },
  {
    "caption": "B - E Quantification of total axon length (WT, n = 13 neurons; Yme1l-/-, n = 13 neurons), total dendritic length (WT, n = 12 neurons; Yme1l-/-, n = 13 neurons), axonal branch points (WT, n = 12 neurons; Yme1l-/-, n = 13 neurons) and number of dendrites (WT, n = 12 neurons; Yme1l-/-, n = 13 neurons). Individual neurons originate from two independent preparations. Unpaired t-test, ns = not significant, *P ≤ 0.05.",
    "ncbi_link": "Yme1l: 27377"
  },
  {
    "caption": "F, G Kymographs showing mitochondrial movements in representative axons. Vertical lines correspond to stationary mitochondria and diagonal lines to moving mitochondria. Mitochondria were stained using Mitotracker. In total 39 axonal segments were analyzed for WT control neurons and 37 axonal segments for Yme1l-/- neurons at DIV7. Data are means of three independent experiments ± SEM. Unpaired t-test, ns = not significant, *P ≤ 0.05.",
    "ncbi_link": "Yme1l: 27377"
  },
  {
    "caption": "H, I Kymographs showing mitochondrial movements in representative axons. Vertical lines correspond to stationary mitochondria and diagonal lines to moving mitochondria. Mitochondria were stained using Mitotracker. In total 120 axonal segments were analyzed for WT control neurons and 107 axonal segments for Yme1l-/- neurons at DIV10-14. Data are means of three independent experiments ± SEM. Unpaired t-test, ns = not significant, *P ≤ 0.05.",
    "ncbi_link": "Yme1l: 27377"
  },
  {
    "caption": "J Axonal area occupied by mitochondria in Yme1l-/- neurons relative to WT controls. In total 120 axonal segments were analyzed for WT control neurons and 107 axonal segments for Yme1l-/- neurons at DIV10-14. Data are means of three independent experiments ± SEM. Unpaired t-test, ns = not significant, *P ≤ 0.05.",
    "ncbi_link": "Yme1l: 27377"
  },
  {
    "caption": "Representative images of eyes and lenses from 6-7 week old WT and mice lacking OMA1 (NOKO) or both YME1L and OMA1 (NYOKO) in the nervous system. Orange dashed lines mark eye morphology. Scale bars 2.5 mm.",
    "ncbi_link": "OMA1: 67013
YME1L: 27377"
  },
  {
    "caption": "B t-SNE plots showing integrated analysis of Prrx1-Cre- (8-week-old mice, n=3 males) and Lepr-Cre-traced (8-week-old mice, n=4 males) cells. Cells were colored by clusters (left) or samples (right). Top 20 PCs were chosen for the clustering.",
    "ncbi_link": "Cre: 2777477
Lepr: 16847
Prrx1: 18933"
  },
  {
    "caption": "E In situ hybridization of Col3a1 on femur sections. Col3a1 was expressed in the perichondral (a) and periosteal (b) regions, but not in the bone marrow. B: Bone; BM: Bone marrow; Peri: Periosteum; Endo: Endosteum. Scale bars were 100 µm. Arrowheads indicated the periosteum.",
    "ncbi_link": "Col3a1: 12825"
  },
  {
    "caption": "F Immunofluorescent images of the distal femur in 8-week-old Lepr-Cre; tdTomato mice. Arrowheads indicated tdTomato+ periosteal cells. Two representative periosteal regions were magnified (a and b). GP: Growth plate. B: Bone. BM: Bone marrow. Peri: Periosteum. Scale bars were 100 µm. G Immunofluorescent images of the distal femur in 8-week-old Lepr-Cre; tdTomato mice 7 days after fracture. Aggrecan (green), tdTomato (red), DAPI (blue). Arrowheads indicated tdTomato+ periosteal cells. Two representative regions were magnified (a and b). Scale bars were 100 µm.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Lepr: 16847"
  },
  {
    "caption": "D Flow cytometry analysis of BrdU incorporation in uncultured Lepr-Cre+Notch3+/- BMSCs (n=4 independent experiments). Eight-week-old Lepr-Cre; tdTomato mice were given a single intraperitoneal injection of BrdU (100 mg/kg body mass) and maintained on 0.5 mg/ml of BrdU in the drinking water for 14 days.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Lepr: 16847
Notch3: 18131"
  },
  {
    "caption": "E Immunofluorescent images of the distal femur in 8-week-old Lepr-Cre; tdTomato mice. Notch3 (green), tdTomato (red), CD31 (gray), DAPI (blue). Sinusoid (a), arteriole (b), artery (c) and avascular bone marrow (BM, d) regions were shown. Arrowheads indicated Notch3+ tdTomato+ adventitial cells closely associated with ECs. Arrows indicated Notch3- tdTomato+ reticular cells in the bone marrow that were not associated with ECs. Scale bars were 10 µm. F Localization quantification of Lepr-Cre+Notch3+ cells relative to bone marrow ECs (n=5 biological replicates from three independent experiments). Cells within 5 µm diameter of ECs were considered adjacent. G",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Lepr: 16847"
  },
  {
    "caption": "F Representative images of adipogenic, osteogenic and chondrogenic differentiation following shRNA knockdown in Lepr-Cre+ BMSCs. Scale bars were 100 µm.",
    "ncbi_link": "Cre: 2777477
Lepr: 16847"
  },
  {
    "caption": "G qPCR analysis of the expression levels of Pparg, Bglap and Acan in control or knockdown group (n=3 independent experiments). The statistical significance of differences was analyzed by one-way ANOVAs with Tukey's multiple comparison tests. Data represented Mean ± SD. *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "Acan: 11595
Bglap: 12096
Pparg: 19016"
  },
  {
    "caption": "F Immunostaining of Sca-1 on femur sections of 8-week-old Lepr-Cre; tdTomato mice. Arrows indicated Sca-1+ tdTomato+ cells inside cortical bones of the femur diaphysis. Arrowheads indicated Sca-1+ tdTomato+ cells in the femur periosteum. B: Bone. BM: Bone marrow. Peri: Periosteum. Scale bars were 100 µm.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Lepr: 16847"
  },
  {
    "caption": "G Representative flow cytometry plots of long bone periosteum in 8-week-old Lepr-Cre; tdTomato mice. The percentage of DAPI- CD45- Ter119- Tie2- tdTomato+ Sca-1+/- cells were shown.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
Lepr: 16847"
  },
  {
    "caption": "A, B Representative oil red staining after 7 days of adipogenic differentiation in Lepr-Cre+ subsets (A) and qPCR analysis of Adipoq and Pparg expression (B) (n=3 independent experiments). Scale bars were 100 µm.",
    "ncbi_link": "Adipoq: 11450
Cre: 2777477
Lepr: 16847
Pparg: 19016"
  },
  {
    "caption": "C, D In vitro chondrogenic differentiation of sorted periosteal cells. Representative alcian blue staining after chondrogenic differentiation for 21 days and cryosection (C). Scale bars were 100 µm. Chondrogenic efficiencies were quantified by qPCR analysis of Acan and Col2a1 expression (D) (n=3 independent experiments).",
    "ncbi_link": "Acan: 11595
Col2a1: 12824"
  },
  {
    "caption": "E, F In vitro osteogenic differentiation of sorted periosteal cells. Representative alizarin red staining after osteogenic differentiation for 14 days. Scale bars were 200 µm. Osteogenic efficiencies were quantified by qPCR analysis of Sp7 and Bglap expression (F) (n=3 independent experiments).",
    "ncbi_link": "Bglap: 12096
Sp7: 170574"
  },
  {
    "caption": "C Upper panel: senescence curve  of a representative est2∆ clone. DNA samples were prepared at the indicated time points  to analyze telomere length (middle panel) and t-circles production (lower panel and graph) during  senescence and cell immortalization. Telomeres  were analyzed by  Southern blot  of the XhoI    cut DNA hybridized with a  TG1-3  probe. The presence of t-circles was monitored by RCA and analyzed by TG1-3 probed dot blot. The graph shows signal intensities of the dots measured with the Fiji software (arbitrary units). Similar results were obtained with at least 16 other est2∆ clones.",
    "ncbi_link": "est2: 851028"
  },
  {
    "caption": "A  Senescence curve of a representative  est2∆ clone and corresponding dot blot  of the  RCA  product hybridized with the indicated subtelomeric  or telomeric  probes.  t-circle  amounts were evaluated based on signal intensity of the dots and were expressed as fold increase over the signal in the absence of Φ29 (lower graph).",
    "ncbi_link": "est2: 851028"
  },
  {
    "caption": "B Senescence  curve of a representative est2∆ clone (upper panel). DNA samples were prepared at the indicated  time points to analyze  telomere length by Southern blot (middle panel) and  t-circles production by  RCA assay performed in the absence of dCTP and dATP.(lower panel). The graph shows signal intensities of the dots measured with the Fiji software (arbitrary units).",
    "ncbi_link": "est2: 851028"
  },
  {
    "caption": "D Quantification of the RCA   product after co-IP of the  C-circles with Nic96-RFP showing the effect of ADA2  deletion. Dot signal intensities were quantified using the Fiji software and were calculated as the percentage of INPUT that was  immunoprecipitated  normalized to est2∆ signals. Relative signals were calculated by setting the mean of est2∆ signals from each independent experiment to 1. Means and s.e.m. of the six independent  co-IPs experiments each with 2-6 clones per genotype are shown. Outliers were removed using ROUT robust outlier test. The p-values from one-way ANOVA were adjusted using the Bonferroni's correction for multiple comparisons. est2∆ versus est2∆ NIC96-RFP (p=0,000007),  est2∆ NIC96-RFP versus   est2∆ ada2∆ NIC96-RFP  (p=0,00012).***P<0,0001.",
    "ncbi_link": "RFP: 
ADA2: 852059
ada2: 852059
est2: 851028
NIC96: 850552"
  },
  {
    "caption": "E Quantification of the RCA  product after co-IP  of the C-circles  with  Nic96-RFP  showing the effect of SUS1  deletion. The graph shows means and s.e.m. of the three independent  co-IPs  with 2-5 clones per genotype. Outliers were removed using ROUT robust outlier test. The p-values from one-way ANOVA were were adjusted using the Bonferroni's correction for multiple comparisons. est2∆ versus est2∆ NIC96-RFP (p=0,002), est2∆ versus est2∆ sus1∆ NIC96-RFP (p= 0,0006). **P<0,001, ***P<0,0001.",
    "ncbi_link": "RFP: 
est2: 851028
NIC96: 850552
SUS1: 1466445
sus1: 1466445"
  },
  {
    "caption": "A Senescence  curves of two  est2∆ and two est2∆ ADA2-Myc  clones used to generate  type II survivors for Co-IP-RCA. This experiment is representative out of the 4 independent experiments performed during this study.",
    "ncbi_link": "Myc: 
ADA2: 852059
est2: 851028"
  },
  {
    "caption": "C Detection of the  C-circles co-immunoprecipitated with Ada2-Myc   in type II survivors. The DNA co-immunoprecipitated  with Ada2-Myc was amplified by RCA, loaded on a dot blot  and detected with a telomeric TG1-3 probe. The numbers above the blot  refer to clones in (A) and correspond to type II survivors   produced in independent cultures. The lower panel shows the efficiency of Ada2-Myc IP analyzed by western blot  with anti-Myc  antibody.",
    "ncbi_link": "Myc: 
Ada2: 852059"
  },
  {
    "caption": "A Mean  senescence profiles of the est2∆ (n=7) and  est2∆ sus1∆ (n=8) clones isolated from the same heterozygous diploid. The error bars are SDs. B Mean  senescence profiles of the  est2∆ (n=10) and est2∆ sac3∆ (n=10) clones isolated from one heterozygous diploid. The error bars are SDs.",
    "ncbi_link": "est2: 851028
sac3: 851737
sus1: 1466445"
  },
  {
    "caption": "A Mean senescence profiles  of the est2∆ (n=10) and est2∆ shs1∆ (n=16) clones. The error bars are SDs. B Mean senescence profiles of the est1∆ (n=6) and  est1∆ bud6∆ (n=7) clones. Est1, similarly to  Est2, is essential for telomere maintenance. est1∆ has been used in this experiment instead of est2∆ because EST2  and BUD6 genes are linked on  chromosome XII. The error bars are SDs.",
    "ncbi_link": "bud6: 851029
BUD6: 851029
est1: 850934
Est1: 850934
EST2: 851028
est2: 851028
Est2: 851028
shs1: 851373"
  },
  {
    "caption": "(d-e) Average levels of (d) mRNA quantified by RNAseq (red) or qRT-PCR (grey) or (e) protein quantified by  mass spectrometry (light green) or  western blot (grey) for select  p53 target genes under oscillatory p53. Data information: , n=2 biological replicates, error bars represent std dev.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(f-g) Average levels of (f) mRNA quantified by  RNAseq (blue) or qRT-PCR  (grey) or (g) protein quantified by  mass spectrometry (dark green) or  western blot (grey) for select p53 target genes under  rising p53. Data information: n=2 biological replicates, error bars represent std dev.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "A In silico analysis of Sirt7 mRNA expression in different tissues of the BXD genetic reference population (www.genenetwork.org). Adr: Adrenal Gland mRNA, Bla: Bladder mRNA, Bone: Bone Tibia mRNA, CNS: CNS mRNA, Cec: Cecum mRNA, Epi: Epididymis mRNA, Eso: Esophagus mRNA, Eye: Eye mRNA, Fat: Peritoneal Fat mRNA, GI: GI Track mRNA, Hea: Heart mRNA, Kid: Kidney mRNA, Liv: Liver mRNA, Lung: Lung mRNA, Mus: Gastrocnemius Muscle mRNA, Ova: Ovary mRNA, Pro: Prostate mRNA, Sal: Salivary Gland mRNA, Skin: Skin Back mRNA, Sn: Sciatic Nerve mRNA, Spl: Spleen mRNA, Tes: Testis mRNA, Thy: Thymus mRNA, Ton: Tongue mRNA, Tra: Trachea mRNA, and Ute: Uterus mRNA.",
    "ncbi_link": "Sirt7: 209011"
  },
  {
    "caption": "B Correlation plot for kidney mRNA expression of Sirt7 and Slc12a7 that codifies KCC4 in the mouse BxD genetic reference population (www.genenetwork.org).",
    "ncbi_link": "Sirt7: 209011
Slc12a7: 20499"
  },
  {
    "caption": "C Oocytes injected with cRNA encoding KCC4 were incubated with NAD+ 200 μM and NAM 10 mM for 4 h. Lysates were immunoprecipitated with an anti-KCC4 antibody and then analyzed by SDS-PAGE/immunoblotting using an anti-acetylated-lysine (AcK) or anti-KCC4 antibody. Non-injected oocytes (UI) were used as a control.",
    "ncbi_link": "KCC4: 10723"
  },
  {
    "caption": "E Oocytes injected with H20 or KCC4 were incubated for the indicated times, and KCC4 protein levels were analyzed by SDS-PAGE/immunoblotting.",
    "ncbi_link": "KCC4: 10723"
  },
  {
    "caption": "F Oocytes were injected with either WT, K114R or K114Q KCC4 and incubated with vehicle (V), NAD+ or NAM for 48 h, and KCC4 protein levels (upper pannel), and activity (lower pannel) were analyzed as in D.",
    "ncbi_link": "KCC4: 10723"
  },
  {
    "caption": "C KCC4 activity was evaluated in Xenopus oocytes injected with cRNA encoding KCC4 and coinjected with either wild-type (SIRT7 WT) or the catalytically inactive SIRT7 (SIRT7 H188Y) for 48 h.",
    "ncbi_link": "KCC4: 10723"
  },
  {
    "caption": "D Oocytes were injected with either KCC4 WT, K114R or K114Q for 48 h and then incubated with vehicle (V), NAD+ or NAM for 24 h, and KCC4 and SIRT7 protein levels were analyzed by SDS-PAGE/immunoblotting.",
    "ncbi_link": "KCC4: 10723"
  },
  {
    "caption": "E Oocytes were injected with either KCC4 WT, K114R or K114Q with and without SIRT7 for 48 h and then incubated with vehicle (V) or NAM for 4 h. After lysis, KCC4 was immunoprecipitated using an anti-KCC4 antibody, and the acetylation status of KCC4 was determined by SDS-PAGE/Western blotting using and anti-acetyl lysine antibody.",
    "ncbi_link": "SIRT7: 209011
KCC4: 10723"
  },
  {
    "caption": "F, G FLAG-KCC4 and SIRT7 were transfected into HEK293 cells and treated for the indicated times with NAD+ (F) or NAM (G) and then analyzed by SDS-PAGE/immunoblotting using an anti-KCC4 or anti-SIRT7 antibody. Non-transfected cells (UT) were used as a control.",
    "ncbi_link": "FLAG: 
SIRT7: 209011
KCC4: 20499"
  },
  {
    "caption": "H FLAG-KCC4 and SIRT7 were transfected into HEK293 cells and treated for the indicated times with NAD+ and NAM. After lysis, KCC4 immunoprecipitation using an anti-FLAG antibody was performed, and the interaction with SIRT7 was determined by SDS-PAGE/Western blotting.",
    "ncbi_link": "FLAG: 
SIRT7: 209011
KCC4: 20499"
  },
  {
    "caption": "I HEK293 cells expressing KCC4 were incubated with NAD+ 200 μM and cycloheximide (CHX) for 0, 3, 6 and 9 h. KCC4 protein levels are shown at the indicated times in cells transfected with a scramble shRNA (+SIRT7) or a shRNA against SIRT7 (-SIRT7).",
    "ncbi_link": "SIRT7: 51547"
  },
  {
    "caption": "A KCC4 acetylation at the indicated pH in HEK293 transfected with KCC4. After lysis, KCC4 was immunoprecipitated using an anti-FLAG antibody, and then analyzed by SDS-PAGE/Western blotting using an anti-acetylated-lysine (AcK) or anti-KCC4 antibody. Non-transfected cells (UT) were used as a control.",
    "ncbi_link": "KCC4: 20499"
  },
  {
    "caption": "B HEK293 cells were transfected with KCC4 together with SIRT7 with a scramble shRNA (-) or a shRNA against SIRT7 (+), and KCC4 activity and protein level were determined at the indicated pH. SIRT7 expression in these conditions is presented in C.",
    "ncbi_link": "SIRT7: 209011
SIRT7: 51547
KCC4: 20499"
  },
  {
    "caption": "A, B Sirt7 mRNA (A) and protein (B) abundance in microdissected renal tubules normalized to Rpl26 or Ponceau, respectively. Enrichment for each segment was previously validated by immunoblotting against segment-specific markers as indicated in material and methods (Spirli et al, 2019).",
    "ncbi_link": "Rpl26: 19941
Sirt7: 209011"
  },
  {
    "caption": "C Immunolocalization of SIRT7 and ATPase in the kidneys of C57BL6 mice with metabolic acidosis (SIRT7, red; ATPase, green; DAPI, Blue). Scale bar: 20 μm. Controls of the specificity of antibodies using kidney of SIRT7-deficient mice are provided in Appendix Fig S4.",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "A KCC4 protein levels were determined in the kidneys of wild-type (SIRT7+/+) and SIRT7-deficient mice (SIRT7-/-). SIRT7 protein expression are absent in the kidneys of SIRT7-deficient mice.",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "B KCC4 protein levels, acetylation status of KCC4, and interaction with SIRT7 in kidneys of SIRT7+/+ and SIRT7-/-mice under normal conditions (Control) or with metabolic acidosis.",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "C Immunolocalization of KCC4 and H-ATPase in the kidneys of SIRT7+/+ and SIRT7-/- mice under normal conditions (Control) or with metabolic acidosis (NH4Cl). (KCC4, red; H-ATPase, green). Scale bar: 20 μm. Cell count was performed automatically using the Gen5 software to report the percentage of KCC4+ cells among H-ATPase+ cells (lower panel).",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "D NCC and NKCC2 protein levels in the kidney of SIRT7+/+ and SIRT7-/- mice under basal conditions.",
    "ncbi_link": "SIRT7: 209011"
  },
  {
    "caption": "a, Expression levels of ISX, TWIST1, Snail1, Fibronectin (FN1), VEGF, and E-cadherin (CDH1) mRNA were examined in a ISX-GFP inducible Tet-ON transformants at 8 h after addition of DOX. Data are presented as mean ± SD in graph (p< 0.001 compared to time point 0h; Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "GFP: 
CDH1: 999
E-cadherin: 999
FN1: 2335
Fibronectin: 2335
ISX: 91464
Snail1: 6615
TWIST1: 7291
VEGF: 7422"
  },
  {
    "caption": "b, Western blotting analysis of the protein levels of ISX, HIF1α, TWIST1, Snail1, Slug, ZEB1, Bmi1, E-cadherin (E-Cad.), Fibronectin, N-cadherin (N-Cad.), Vimentin, and VEGF in A549 and H1299 cells with DOX-inducible ISX expression system 8hs after DOX induction.",
    "ncbi_link": "ISX: 91464"
  },
  {
    "caption": "ISX transcriptionally activates luciferase activity driven by TWIST1 (c) promoter regions in A549 cells. Data are presented as mean ± SD in bar graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "ISX: 91464
TWIST1: 7291"
  },
  {
    "caption": "d, ISX transcriptionally activates luciferase activity driven by Snail1 (d) promoter regions in A549 cells. Data are presented as mean ± SD in bar graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "ISX: 91464
Snail1: 6615"
  },
  {
    "caption": "e, ChIP analysis of ISX binding to the TWIST1 promoter region in A549 and H1299 cells (10% input of each groups were pull down and applied to qPCR). Data are presented as mean ± SD in bar graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "ISX: 91464
TWIST1: 7291"
  },
  {
    "caption": "f, ISX transactivation activity analyzed by luciferase activity driven by the TWIST1 promoter. Data are presented as mean ± SD in graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "ISX: 91464
TWIST1: 7291"
  },
  {
    "caption": "g, ChIP analysis of ISX binding to the endogenous promoters of TWIST1 (-180/+35) and Snail1(-160/+40) in A549 and cells (10% input of each groups were pull down and applied to qPCR). Data are presented as mean ± SD in bar graph (p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate.",
    "ncbi_link": "ISX: 91464
Snail1: 6615
TWIST1: 7291"
  },
  {
    "caption": "h, Effect of forced expression and knockdown of ISX on cell migration (wound healing) measured in A549 cells. ISXi, ISX-specific shRNAi Data are presented as mean ± SD in graph (**, p < 0.01, ***, p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm.",
    "ncbi_link": "ISX: 91464"
  },
  {
    "caption": "i, Effect of forced expression and knockdown of ISX on cell invasion (transwell) activity measured in A549 cells. Data are presented as mean ± SD in bar graph (***, p < 0.001 , Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm.",
    "ncbi_link": "ISX: 91464"
  },
  {
    "caption": "e, Western blotting analysis of the protein levels of ISX, PCAF, and EMT markers in DOX-inducible ISX expression system A549 cells treated with TH1834, Garcinol, C646, MB-3 for 8 h after DOX induction. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "ISX: 91464"
  },
  {
    "caption": "g, Western blotting analysis of the protein levels of ISX, PCAF, and EMT markers in A549 cells with PCAF knockdown and DOX-inducible ISX expression system at 8 h time point after DOX induction. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "ISX: 91464
PCAF: 8850"
  },
  {
    "caption": "The cell migration (wound healing, g) activity were determined in A549 cells with GFP-tagged wild or ISX mutants. Data are presented as mean ± SD in graph (***, p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
ISX: 91464"
  },
  {
    "caption": "h, The cell invasion (transwell, h) activity were determined in A549 cells with GFP-tagged wild or ISX mutants. Data are presented as mean ± SD in graph (***, p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Scale bar, 100μm. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
ISX: 91464"
  },
  {
    "caption": "j. Tumor xenografts metastasis activity of constitutively expressing RFP A549 cells transfected with wild type or ISX AC3 mutant cDNA were imaged by IVIS imaging system at fifth weeks Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "ISX: 91464"
  },
  {
    "caption": "k, Kaplan-Meier survival curve analysis of nude mice xenograft injected with A549 cells carrying GFP, ISX-GFP and ISX Ac-GFP (AC3) (n = 10). p = 0.0003. p‐values were calculated by log‐rank (Mantel-Cox) test comparing the two Kaplan-Meier curves. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
ISX: 91464"
  },
  {
    "caption": "d, The mCherry-tagged WT and BRD4 mutants were detected in anti-GFP immunoprecipitates by Western blotting in A549 cells. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "mCherry: 
BRD4: 23476"
  },
  {
    "caption": "e and f, The mRNA levels of TWIST1(e) and Snail1(f) were verified in A549 cells co-expressing mCherry-tagged WT or mutant BRD4 and GFP-tagged ISX by RT-PCR. Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
mCherry: 
BRD4: 23476
ISX: 91464
Snail1: 6615
TWIST1: 7291"
  },
  {
    "caption": "g and h, The DNA binding activity of TWIST1 and Snail1 were evaluated in anti-GFP-mCherry ChIP-ChIP immunoprecipitates by RT-PCR in A549 cells. Red, Hprt1 promoter (-190/+40 bp, negative control) (10% input of each groups were pulled down and used for qPCR analysis). Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "Hprt1: 3251
Snail1: 6615
TWIST1: 7291"
  },
  {
    "caption": "i, The cell invasion (transwell) activity were determined in A549 cells co-transfected with cDNA coding for GFP-tagged ISX and mCherry-tagged BRD4 mutants. Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
mCherry: 
BRD4: 23476
ISX: 91464"
  },
  {
    "caption": "The DNA binding activity of Snail (b) were evaluated in anti-GFP-mCherry ChIP-ChIP immunoprecipitates by RT-PCR in A549 cells. Red, Hprt1 promoter (-190-+40 bp, negative control). (10% input of each groups were pull down and applied to qPCR) Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "Hprt1: 3251
Snail: 6615"
  },
  {
    "caption": "c, The DNA binding activity of TWIST1 (c) were evaluated in anti-GFP-mCherry ChIP-ChIP immunoprecipitates by RT-PCR in A549 cells. Red, Hprt1 promoter (-190-+40 bp, negative control). (10% input of each groups were pull down and applied to qPCR) Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "Hprt1: 3251
TWIST1: 7291"
  },
  {
    "caption": "The cell migration (wound healing, d) activity were determined in A549 cells co-transfected with cDNAs for GFP-tagged ISX and mCherry-tagged BRD4 mutants. Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
mCherry: 
BRD4: 23476
ISX: 91464"
  },
  {
    "caption": "e, The cell invasion (transwell, e) activity were determined in A549 cells co-transfected with cDNAs for GFP-tagged ISX and mCherry-tagged BRD4 mutants. Data are presented as mean ± SD in bar graph (p < 0.001, Student's t‐test) of 3 independent experiments, each performed in triplicate. Data information: Each experiment was repeated at least three times.",
    "ncbi_link": "GFP: 
mCherry: 
BRD4: 23476
ISX: 91464"
  },
  {
    "caption": "Correlation analysis of mRNA expression for, (d) ISX and BRD4, in 157 lung cancer samples.",
    "ncbi_link": "BRD4: 23476
ISX: 91464"
  },
  {
    "caption": "e, Correlation analysis of mRNA expression for, (e) ISX and PCAF in 157 lung cancer samples.",
    "ncbi_link": "ISX: 91464
PCAF: 8850"
  },
  {
    "caption": "(B) VVA lectin immunoblot of secretomes from HepG2 SC, SCΔT1, SCΔT2 and SCΔT3.",
    "ncbi_link": "T1: 2589
T2: 2590
T3: 2591"
  },
  {
    "caption": "Histograms showing the distribution of M/L quantitation ratios of monoglycosylated peptides identified in (A) HepG2SCΔT1, (B) ΔT2 and (C) +T3. Glycopeptides with M/L ratio < -1 are colored red and glycopeptides with a M/L ratio > +1 are colored green. (D) Venn diagram showing the distribution of candidates for isoform-specific sites among HepG2SCΔT1, T2 and +T3 applying a log10 (+/-1) cut-off (excluding sites identified in both TCL and SEC for each isoform), and (E) TCL alone and (F) SEC alone.",
    "ncbi_link": "T1: 2589
T2: 2590
T3: 2591"
  },
  {
    "caption": "(H and I) Representative GUS staining images of cotyledons (H) and quantification of the relative HR efficiency (I). The reporter line and trigger line in either ddrm4-1 or Col-0 background were crossed and the F1 seedlings were used for GUS staining analysis. Scale bar = 1 mm. The number of blue sectors was scored. The data are presented as means ± SD (n > 132 cotyledons) relative to the values of Col-0. The statistical significance was determined using two-tailed Students' t-test. ****, P < 0.0001.",
    "ncbi_link": "ddrm4: 844312"
  },
  {
    "caption": "(K) eChIP-qPCR assays. The immunoprecipitated DNA and the input DNA were subjected to qPCR analysis. The ratios of eChIP and input are shown. UBQ5 serves as a negative control. The positions of the PCR fragment of 0.5 kb-4.5 kb were shown in (I). The data are represented as means ± SD (n = 3 technical replicates) relative to the values of Mock. The statistical significance was determined using two-tailed Students' t-test. ns, not significant; **, P < 0.01; ***, P < 0.001. The experiments were repeated three times with similar results.",
    "ncbi_link": "UBQ5: 825398"
  },
  {
    "caption": "(A and B) Yeast two-hybrid assays. PAF1 was fused with the activation domain (AD). SMC5 and SMC6B were fused with the DNA binding domain (BD). DDO, double dropout (SD/-Trp/-Leu) medium. QDO, quadruple dropout (SD/-Trp/-Leu/-His/-Ade) medium.",
    "ncbi_link": "PAF1: 844312
SMC6B: 836267
SMC5: 831449"
  },
  {
    "caption": "The PAF1 foci are dependent on SMC5 and SMC6B. (A) CFP-PAF1 was transfected alone or co-transfected with the RNAi construct of SMC5 (SMC5-Ri) into Col-0 protoplasts. (C) CFP-PAF1 was transfected into the protoplasts of Col-0 or smc6b, respectively. The protoplasts were treated with 20 μM BLE for 2 h before imaging. The percentage of cells with foci. The data were represented as means ± SEM (n = 3 biological replicates). For each sample, at least 32 cells were scored. The statistical significance was determined using two-way ANOVA analysis. **, P < 0.01; ***, P < 0.001.",
    "ncbi_link": "CFP: 
PAF1: 844312
smc6b: 836267
SMC6B: 836267
SMC5: 831449"
  },
  {
    "caption": "(G and H) eChIP-qPCR assays. (G) The SMC5-Ri construct was transfected into the protoplasts of SSDIS/CFP-PAF1 transgenic plants. (H) The 35S:CFP-PAF1 construct was transfected into the protoplasts of SSDIS/smc6b or SSDIS/Col-0 transgenic plants. The protoplasts were treated with 100 μM DEX for 4 h to induce DSBs. The eChIP assays were carried out using an anti-GFP antibody. The immunoprecipitated DNA (eChIP) and the input DNA were subjected to qPCR analysis. The ratios of eChIP and input are shown. UBQ5 serves as a negative control. The data are represented as means ± SD (n = 3 technical replicates). The statistical significance was determined using two-tailed Students' t-test. ns, not significant; ****, P < 0.0001.",
    "ncbi_link": "CFP: 
PAF1: 844312
smc6b: 836267
SMC5: 831449
UBQ5: 825398"
  },
  {
    "caption": "(I and J) The UBC2 foci are dependent on VIP5. UBC2-mCherry and/or VIP5-YFP were transfected into the vip5 protoplasts. The protoplasts were treated with 20 μM BLE for 2 h before imaging. Scale bars = 2.5 μm. The data in (J) were represented as means ± SEM (n = 3 biological replicates). For each sample, at least 30 cells were scored. The statistical significance was determined using two-way ANOVA analysis. ****, P < 0.0001. All experiments were repeated at least three times with similar results.",
    "ncbi_link": "mCherry: 
YFP: 
UBC2: 814805
vip5: 842395
VIP5: 842395"
  },
  {
    "caption": "(E-J) The HUB1/2 foci are dependent on UBC2. VIP5-CFP, HUB1/2-YFP, and/or UBC2-mCherry were transfected into the ubc1 ubc2-c1 protoplasts. The protoplasts were treated with 20 μM BLE for 2 h before imaging. Bars = 2.5 μm. The data in (F, G, I, and J) were represented as means ± SEM (n = 3 biological replicates). For each sample, at least 60 cells were scored. The statistical significance was determined using two-way ANOVA analysis. ns, not significant; **, P < 0.01.",
    "ncbi_link": "CFP: 
mCherry: 
YFP: 
HUB1: 819104
ubc1: 838002
UBC2: 814805
ubc2: 814805
VIP5: 842395"
  },
  {
    "caption": "(I and J) eChIP-qPCR assays. (I) The SSDIS/Col-0 transgenic Arabidopsis was mock-treated or treated with 100 μM DEX for 4 h. (J) The SSDIS/Col-0 and SSDIS/ddrm4-1 transgenic Arabidopsis were treated with 100 μM DEX for 4 h. The eChIP assays were carried out using an anti-H2Bub antibody. The immunoprecipitated DNA (eChIP) and the input DNA were subjected to qPCR analysis. The ratios of eChIP and input are shown. UBQ5 serves as a negative control. The data are represented as means ± SD (n = 3 technical replicates). (I) The data are relative to the values of Mock. (J) The data are relative to the values of UBQ5 in Col-0. The statistical significance was determined using two-tailed Students' t-test. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. The experiments were repeated at least twice with similar results.",
    "ncbi_link": "ddrm4: 844312
UBQ5: 825398"
  },
  {
    "caption": "B) Histological sections of 3 IDHwt PDXs (P3, T434, P8) and 3 IDHm PDXs ((T394, E478, T186) showing a large ROI (boxed rectangle, >500 pixels) within the tumor area applied for targeted quantification of selected metabolites. Left rectangle in P3 PDX was used as control contralateral brain (CB) for quantifications. Middle panel shows tissue distribution of D-2-hydroxyglutarate (D2HG) by MSI, which is exclusively detected in IDHm PDXs (D2HG in IDHwt tumours is below detection limit). Right panel shows tissue distribution of a key metabolite (m/z 778.51) presenting strong accumulation in IDHm lower grade gliomas (LGG) versus glioblastomas (GBM) independent of IDH status. An intensity-dependent color code indicates the relative amount of a specific compound (defined by m/z value) throughout the tissue section.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "C) Quantification of several high mass metabolites differentially present in IDHm PDXs (IDHwt glioblastomas (GBM) in blue, IDHm GBM in orange, IDHm lower grade gliomas (LGG) in red, contralateral control brain (CB) in grey). Box plots represent log values of metabolite intensities measured within a large ROI (>500 pixels). Many metabolites in this mass range (m/z 700-900) have been putatively assigned to phospholipids (Tables EV2-3). m/z represents the mass over charge ratio of ionized metabolites, as measured by the mass spectrometer. Except where otherwise indicated, statistical significance was calculated for IDHm (n=3) versus IDHwt (n=3) PDXs using T test. pv: p-values.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "A) MALDI imaging of indicated metabolites in IDHwt PDX (P3), IDHm PDX (E478) and control brain (CB). Hex-P: hexose-phosphate; AMP, ADP, ATP: adenosine mono-, di- and triphosphate respectively.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "B) LC-MS quantification of indicated metabolites in 6 PDXs. Relative quantities of metabolites are expressed in log scale and normalized to tissue quantity used for extract preparation. IDHwt glioblastomas (GBM) in blue, IDHm GBM in orange, IDHm lower grade gliomas (LGG) in red, contralateral control brain (CB) in grey. Sdh7-P: sedoheptulose-7-phosphate.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "A) LC-MS quantification of steady-state level of glycolysis and TCA cycle metabolites in three IDH1wt and three IDH1m PDXs and contralateral control brain (CB) (n=3/ sample/ group). Metabolites showing statistically significant group differences between IDH1wt and IDH1m are indicated (pvalue: * <0.05). Color code as in Fig. 1-2.",
    "ncbi_link": "IDH1: 15926"
  },
  {
    "caption": "C) In vivo flux analysis of 13C-labelled glucose injected 20 minutes prior to sacrifice in one IDH1wt PDX (P3) and one IDH1m PDX (E478) (n=3/ sample). The percentage of glucose-derived 13C label is shown in selected metabolites containing 0 to 6 13C atoms (13C0 - 13C6 as indicated by color code). Note the absence of 13C2 label of αKG and D2HG in IDHm tumours, while the label was detectable in IDHwt PDX and in contralateral brain of both tumors (lower panel).",
    "ncbi_link": "IDH: 15926
IDH1: 15926"
  },
  {
    "caption": "A) MALDI imaging of key metabolites in IDHwt (P3) and IDHm (E478) glioma PDX, compared to control brain (CB) sections.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "B) Quantification of metabolite distribution by MSI in 6 PDX with IDH1wt and IDH1m status (n=3 / group) and in contralateral control brain (CB). No significant differences between IDH groups were detected, although significant differences are found between tumors and control brain (glutamate, apsartate). Color code as in Fig. 1, NAA: N-acetylaspartic acid; NAAG: N-acetylaspartylglutamic acid.",
    "ncbi_link": "IDH: 15926
IDH1: 15926"
  },
  {
    "caption": "A) NADPH levels are reduced in IDHm compared to wildtype tumors, resulting in a reduced NADPH/NAD+ ratio (n=3/ sample). p-value from T test: *<0.05. NADPH, NADP: reduced, oxydized nicotinamide adenine dinucleotide phosphate, NADH, NAD: reduced, oxydized nicotinamide adenine dinucleotide.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "B) MALDI images for glutathione (GSH) and cystathionine on IDHwt (P3) and IDHm (E478) PDXs.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "D) LC-MS quantification of independent samples for GSH, GSSG (oxidized GSH), GSSG/GSH ratio and cystathionine from 6 PDXs (n=3/ sample / group). Statistical significance between IDH groups calculated by T test, pv: p-value.",
    "ncbi_link": "IDH: 15926"
  },
  {
    "caption": "A) Comparative gene expression analysis of key enzymes involved in GSH and cysteine synthesis and supply in IDHwt (n=220), IDHm with 1p/19q co-deletion (n=151) or IDHm without 1p/19q co-deletion (n=226) patients based on TCGA RNA-seq data from a cohort of 597 patients. CBS: Cystathionine beta synthase, key enzyme of the transsulfuration pathway. GCLC: catalytic subunit of glutamate-cysteine ligase. SLC7A11: gene encoding xCT, the cystine-glutamate antiporter.",
    "ncbi_link": "CBS: 875
GCLC: 2729
IDH: 3417
SLC7A11: 23657"
  },
  {
    "caption": "B) Kaplan-Meier curves of CBS gene expression versus overall survival in patients with IDHwt, IDHm with or without 1p/19q co-deletion. Statistical significance for the survival analysis is shown as: pv: p-value, ns= non significant.",
    "ncbi_link": "CBS: 875
IDH: 3417"
  },
  {
    "caption": "(B) Effect of MBCD on total rates of protein degradation, measured as in (A), in wild‐type mouse fibroblasts and in fibroblasts stably RNA interfered for LAMP‐2A (LAMP‐2A(−)). The ratio of degradation in MBCD‐treated and untreated cells is shown for cells maintained with or without 10 mM 3‐methyladenine (3MA).",
    "ncbi_link": "LAMP‐2A: 16784"
  },
  {
    "caption": "(D) The percentage of total lysosomal hLAMP‐2A present in each fraction was determined by densitometric quantification of immunoblots as the ones shown here. Values, corrected for the amount of mLAMP‐2A in each fraction, are mean+s.e. of 3-4 experiments.",
    "ncbi_link": "LAMP‐2A: 3920"
  },
  {
    "caption": "(F) Proteolysis of a pool of 3[H]labeled cytosolic proteins by intact (left) or disrupted (right) lysosomes isolated from untransfected mouse fibroblasts (none) or fibroblasts transfected with wild‐type (WT) or the indicated mutant forms of hLAMP‐2A. Values are the mean+s.e. of two experiments with triplicate samples.",
    "ncbi_link": "LAMP‐2A: 3920"
  },
  {
    "caption": "B Relative abundance of mRNA for the cyp-34A4 gene. Values are based on qRT-PCR analysis, with the relative levels for each gene normalized to the value observed in the wild-type control. ***P<0.001, ANOVA with Dunnett's posthoc comparison to wild type. N=3 trials. Error bars indicate SEM.",
    "ncbi_link": "cyp-34A4: 188350"
  },
  {
    "caption": "F Quantified fluorescence as in (B) for animals exposed to the indicated RNAi vector or empty vector (EV) control, and in either a wild type (WT) or fat-1(wa9) genetic background. *P<0.001, ANOVA with Dunnett's posthoc comparison to the wild-type control equivalent time point. N=20 animals per genotype and time point. Error bars indicate SEM.",
    "ncbi_link": "fat-1: 178291"
  },
  {
    "caption": "A) Gene expression of multiple cachexia-associated markers in gastrocnemius muscles of individual animals from Study 1 (n=5 for tumor-bearing groups; n=6 for tumor-free groups). Expression was determined by qRT-PCR and presented as described in the Materials and Methods (Geometric Mean ± Geometric STD). B) Androgen receptor (AR) mRNA expression in gastrocnemius muscles from Study 1. Statistics: p values provided in Appendix Table S5A-B. Dunnett's multiple comparison test. CEBPδ, n=4, insufficient sample to analyze all tumor-bearing GTx-024-treated animals.",
    "ncbi_link": "Androgen receptor: 11835
AR: 11835
CEBPδ: 12609"
  },
  {
    "caption": "C) Significance values from GSEA using combined STAT3 gene sets identified in B. Each treatment group is compared to tumor-bearing control (cachexia) transcriptomes.",
    "ncbi_link": "STAT3: 20848"
  },
  {
    "caption": "D) Heat map of DEGs within the combined STAT3 gene sets representing mean z scores calculated from normalized RNAseq count data. Tumor-free control (black checkered), GTx-024-treated tumor-free (blue checkered), tumor-bearing control (black), GTx-024-treated tumor-bearing (blue), AR-42-treated tumor-bearing (red) and Combination-treated tumor-bearing (green).",
    "ncbi_link": "STAT3: 20848"
  },
  {
    "caption": "E) Results of GSEA using combined ATF-1 gene sets identified in B across treatment groups versus tumor-bearing control (cachexia) transcriptomes.",
    "ncbi_link": "ATF-1: 11908"
  },
  {
    "caption": "Tumor-free control (black checkered), GTx-024-treated tumor-free (blue checkered), tumor-bearing control (black), GTx-024-treated tumor-bearing (blue), AR-42-treated tumor-bearing (red) and Combination-treated tumor-bearing (green). F) Heat map of DEGs within the combined ATF-1 gene sets (mean z score). Treatment groups are as in D.",
    "ncbi_link": "ATF-1: 11908"
  },
  {
    "caption": "G) mRNA expression of mediators of IL-6 signaling upstream of STAT3. Data presented as mean±SD of per animal log-transformed fold change (log2FC) values versus tumor-free controls. Groups: Tumor-free control (n=6), tumor-free GTx-024 treated (n=5), tumor-bearing receiving vehicle (n=4), GTx-024 (n=5), AR-42 (n=5) or Combination (n=6).",
    "ncbi_link": "IL-6: 16193
STAT3: 20848"
  },
  {
    "caption": "C) Significance values from GSEA using combined CTNNB1 gene sets. Each treatment group was compared to tumor-free control transcriptomes. *FDR < 1e-5 determined, set to 1e-5 for plot.",
    "ncbi_link": "CTNNB1: 12387"
  },
  {
    "caption": "D) Enrichment plots from GSEA of the CTNNB1 gene set for each treatment group versus tumor-free control comparisons. GTx-024-treated tumor-free (blue checkered), tumor-bearing control (black), GTx-024-treated tumor-bearing (blue), AR-42-treated tumor-bearing (red) and Combination-treated tumor-bearing (green).",
    "ncbi_link": "CTNNB1: 12387"
  },
  {
    "caption": "E) mRNA expression of WNT effectors upstream of β-catenin. Data are presented as mean±SD of log-transformed fold change (log2FC) values versus tumor-free controls. Groups: Tumor-free control (n=6), tumor-free GTx-024 treated (n=5), tumor-bearing receiving vehicle (n=4), GTx-024 (n=5), AR-42 (n=5) or Combination (n=6).",
    "ncbi_link": "β-catenin: 12387"
  },
  {
    "caption": ", B. survival of Ssrp1fl/fl; CreERT2+/+ mice  of different  ages (weeks) after the start of tamoxifen (TMX) treatment. B.  Kaplan-Meier survival curves. Log-rank test p = 0.032 for the oldest male age group versus all other  male  groups; p = 0.013 for all females versus all males; for all other comparisons p > 0.05. n = 6-10 mice.",
    "ncbi_link": "Cre: 2777477
ERT2: 5595
Ssrp1: 20833"
  },
  {
    "caption": "C. Normalized  blood cell counts in Ssrp1fl/fl; CreERT2+/+ mice treated with vehicle or tamoxifen on day 7 after start of treatment. Mean ± SD, * indicates p < 0.05 (unpaired t-test). n = 3 mice.",
    "ncbi_link": "Cre: 2777477
ERT2: 5595
Ssrp1: 20833"
  },
  {
    "caption": "A, B. Effect of tamoxifen on replication in the spleen (A) and  intestine (B) of Ssrp1fl/fl; CreERT2+/+ mice.  EdU was given to  mice three days after the end of tamoxifen  treatment (1 hour before tissue collection). Organ sections were  stained  for total DNA  (Hoechst), EdU, and SSRP1. Scale bars - 100 μM. C. Quantitation of  EdU staining. Mean number of EdU positive cells per field of view +/- SD. n > 5 fields of view per mouse. 3 mice were analyzed. D. Quantitation of cleaved caspase-3 staining. Mean number of positive cells per fields of view +/- SD, n > 5 fields of view per mouse Two male and female mice  were analyzed. Data information: P-values for C and D were calculated using the unpaired t-test.",
    "ncbi_link": "Cre: 2777477
ERT2: 5595
Ssrp1: 20833"
  },
  {
    "caption": "D. UMAP plots with color-coded  intestinal stem cells identified by transcriptional signatures of intestinal stem cells or by expression  of Lgr5  or Gkn3 genes.",
    "ncbi_link": "Gkn3: 68888
Lgr5: 14160"
  },
  {
    "caption": "F, G. Effect of  4-OHT  administration on  intestinal organoids of different genotypes kept in the presence (undifferentiated) or absence (differentiated) of R-spondin-1. F. The  viability of organoids assessed by the resorufin  assay. Mean ± SD, n = 3 wells per mouse. P < 0.05 are shown (unpaired t-test). Organoids were isolated from two  mice  of each genotype. G. IF images of  intestinal organoids from Ssrp1fl/fl; CreERT2+/+ mice kept in the presence or absence of R-Spondin-1. The  organoids  were stained  with antibodies to  LGR5 and SSRP1  and counterstained  with Hoechst (DNA).",
    "ncbi_link": "Cre: 2777477
ERT2: 5595
Ssrp1: 20833"
  },
  {
    "caption": " B) Dyads of metaphase II chromosome spreads of control, Bub1KD, Mps1∆N and Reversine-treated oocytes (from GVBD onwards) stained with Sgo2 antibody (red), CREST serum (green) and Hoechst (blue). ",
    "ncbi_link": "Bub1: 12236
Mps1: 17476"
  },
  {
    "caption": " A) Metaphase II oocytes from mice carrying a conditional, oocyte-specific invalidation of separase (Separaseflox/flox Zp3 Cre+, or Sep-/-) and oocytes from litter mates (Separaseflox/flox, or Sep+/+) were obtained after superovulation. In vivo matured control (Sep+/+) and Sep-/- oocytes are found in oviducts at comparable numbers, enclosed by cumulus cells. Example of cumulus enclosed oocytes from the oviduct is shown below. In (A), n indicates the number of mice and a mean number of oocytes per mouse of each genotype, error bars are + s.e.m. ",
    "ncbi_link": "Sep: 105988
separase: 105988
Separase: 105988
Zp3: 22788"
  },
  {
    "caption": " D) Metaphase-to-anaphase transition of meiosis II in oocytes of the indicated genotype cultured in vitro and injected with the separase constructs as indicated, in GV. The schemes indicate the chromosome figures observed upon activation. Chromosome spreads are stained with CREST serum (green), and Rec8 antibody (red). DNA was stained with DAPI (blue). In (D) n indicates the number of oocytes with the shown phenotype (e.g., upon successful activation) and the total number of oocytes analyzed. ",
    "ncbi_link": "separase: 105988"
  },
  {
    "caption": " A) Sep+/+ or Sep-/- oocytes were matured in vitro until metaphase II. Sep-/- oocytes were injected with wild-type separase or cleavage mutant separase encoding mRNAs in metaphase II. Oocytes were either fixed in metaphase II or activated and fixed in anaphase II. Spreads were stained with Rec8 antibody (red), CREST serum (green), and DAPI (blue) to label DNA. n indicates the number of oocytes with the shown phenotype (e.g. in anaphase II, after successful activation) and the total number of oocytes analysed ",
    "ncbi_link": "Sep: 105988
separase: 105988"
  },
  {
    "caption": " B) Representative image of kinetochore individualization in Sep-/- oocytes injected with wild-type separase in metaphase II and fixed after activation, from A). Shown is staining with CREST serum (green), and DAPI (blue) to label DNA. Arrows indicate separated sister kinetochores. The scheme on the left illustrates the individualization of sister kinetochores (green arrows) at anaphase II. n indicates the number of oocytes with the shown phenotype (e.g. in anaphase II, after successful activation) and the total number of oocytes analysed Scale bars: 10 µm, except bottom panel in B), where the scale bar is 2 μm. ",
    "ncbi_link": "Sep: 105988
separase: 105988"
  },
  {
    "caption": " A) Live imaging movie of GFP-Sgo2 expressing oocytes (from GV onwards) undergoing meiosis I. The green channel to visualize GFP-Sgo2 localized to chromosomes is shown. Timepoints were taken every 10min, shown is a montage of selected frames such as indicated (hours: time after GVBD) at the metaphase-to-anaphase transition of meiosis I and in metaphase II. Each timepoint is comprised of an overlay of 11 z-sections of 3μm for GFP. The arrow heads indicate bivalents. In (A-C) n indicates the number of control non-injected and GFP-Sgo2-expressing oocytes analyzed ",
    "ncbi_link": "GFP: 
Sgo2: 68549"
  },
  {
    "caption": " C) Metaphase I (4hrs after GVBD) and II spreads after GFP-Sgo2 expression (from GV onwards). Spreads were stained with CREST serum (red), Hoechst for DNA (grey), GFP-Sgo2 was visualized by GFP fluorescence (green). Arrowheads mark separated sister kinetochores. On the right, graph showing percentage of metaphase II spreads containing bivalent chromosomes. In (A-C) n indicates the number of control non-injected and GFP -Sgo2-expressing oocytes analyzed The number of analysed oocytes in C)",
    "ncbi_link": "GFP: 
Sgo2: 68549"
  },
  {
    "caption": " D) Chromosome spreads of oocytes expressing GFP-Sgo2 (from GV onwards) in metaphase II, and upon activation. Spreads were labeled with Rec8 antibody (shown in red, far-red secondary antibody was used), CREST serum (pseudo-colored in green), and Hoechst (blue). GFP direct fluorescence was imaged for GFP-Sgo2 detection. Below the corresponding chromosome figures are represented in the schemes. E) Quantification of Rec8 signal found around and in between CREST signals that were close to each other. Below: scheme illustrating how Rec8 signals (in red) were measured at the indicated meiotic stages. Ifluor stands for a mean fluorescence intensity of the area within the box (dotted lines). Meta: metaphase, ana: anaphase. D), the number of oocytes with the shown phenotype and the total number of oocytes analyzed. On each graph, mean is shown, error bars are +s.e.m. in C) and and ± SD in E), asterisks indicate significant difference (**** = p<0,0001) according to Mann-Whitney U test. AU: arbitrary units. The number of analysed kinetochore pairs in E) is indicated.",
    "ncbi_link": "GFP: 
Sgo2: 68549"
  },
  {
    "caption": "A HEK 293 cells were transfected with mCherry-tagged Parkin and FLAG-tagged UBQLN2 for 24 h, and then were treated with 5 µg/mL Antimycin A and Oligomycin A (A/O) for 4 h and 24 h. The cells were stained with anti-FLAG (green) antibody and anti-TOM20 (gray), and then were visualized using confocal microscopy. Scale bars, 10 µm. Insets were higher magnifications of the dashed box area. Scale bars, 2.5 µm. B, C The dashed square is magnified as shown in the boxed region in A with corresponding line scan indicating Parkin and UBQLN2 co-localization on the depolarized mitochondria (the line scan indicates pixel intensity of Parkin and UBQLN2).",
    "ncbi_link": "FLAG: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "D HEK 293 cells were transfected with mCherry-tagged Parkin and EGFP-tagged UBQLN2. 24 h after transfection, cells were treated with 1 µg/mL A/O for 4 h, and then were harvested for the isolation of mitochondria. Whole cell (Total), cytosol (Cyto) and mitochondria (Mito) were lysed and analyzed by western blotting with the indicated antibodies.",
    "ncbi_link": "EGFP: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "A Domain structure of Parkin in upper region. HEK 293 cells were transfected with HA-tagged UBQLN2 and FLAG-tagged Parkin WT or mutants (K161N, T240R, C418R, C431F and P437L) for 24 h, and then were treated with 5 µg/mL A/O for 5 h. The cells were stained with anti-HA (green) and FLAG (red) antibodies. Then the cells were visualized using confocal microscopy. Scale bars, 10 µm. Lower panel were higher magnifications of the dashed box area. Scale bars, 2.5 µm. B, C The quantification data of the Parkin or UBQLN2 with mitochondrial localization in A. At least 60 anti-HA-UBQLN2 or anti-FLAG-Parkin positive cells were counted for each sample. Data from three independent experiments were represented as means ± SD., ns, not significantly different; **, p<0.01; ***, p<0.001, one-way ANOVA.",
    "ncbi_link": "FLAG: 
HA: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "B HEK 293 cells were transfected with indicated siRNA. After 48 h, the cells were re-transfected with FLAG-Parkin and mt-mKeima for 17 h. Then the cells were treated with 5 µg/mL A/O for 5 h, and visualized using confocal microscopy. Intracellular mt-mKeima signal excited at 458 nm (measuring mitochondria with a neutral pH) was shown in green color, while red color indicated the mt-mKeima fluorescence excited at 561 nm (measuring mitochondria with an acidic pH) in the same cell. Scale bars, 10 µm.",
    "ncbi_link": "FLAG: 
Parkin: 5071"
  },
  {
    "caption": "G HEK 293 cells were transfected with indicated siRNAs. After 24 h, the cells were re-transfected with FLAG tag or FLAG-tagged UBQLN2WT or ∆UBA, along with mCherry-Parkin for 24 h. The cells then were treated with or without 1 µg/mL A/O for 24 h. The cell lysates were subjected to immunoblot with indicated antibodies.",
    "ncbi_link": "FLAG: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "A Domain structure of UBQLN2 in upper region. HEK 293 cells were transfected with FLAG-tagged UBQLN2-WT or ALS-linked mutants (∆UBA, ∆UBL, P497H or P509S), along with mCherry-Parkin. After 24 h, the cells were treated with 5 µg/mL A/O for 5 h. The cells were stained with anti-FLAG (green) and anti-TOM20 (gray) antibodies, and then were visualized using confocal microscopy. Scale bars, 10 µm. Insets were higher magnifications of the dashed box area. Scale bars, 2.5 µm.",
    "ncbi_link": "FLAG: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "C The cells were transfected with mCherry-Parkin and HA-tagged UBQLN2-WT or ALS-mutants as A and subjected to immunofluorescent assay as in A, but were treated with 1 µg/mL A/O for 24 h. Scale bar, 10 µm. Yellow arrow indicates uncleared mitochondria.",
    "ncbi_link": "HA: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "E HEK 293T cells were transfected with indicated siRNAs. After 24 h, the cells were re-transfected with FLAG-tagged UBQLN2-WT or mutants, along with mCherry-Parkin for 24h. Then the cells were treated with or without 1 µg/mL A/O for 18 h. The cell lysates were subjected to immunoblot with indicated antibodies.",
    "ncbi_link": "FLAG: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "A HEK 293 cells were transfected with mCherry-tagged Parkin, HA-tagged UBQLN2, FLAG-tagged HSP70 and BFP-mito for 24 h, and were then treated with 5 µg/mL A/O for 4 h. The cells were stained with anti-HA (green) and FLAG (gray) antibodies, and were visualized using confocal microscopy. Scale bar, 10 µm. Right panel were higher magnifications of the dashed box area. Scale bars, 2.5 µm.",
    "ncbi_link": "FLAG: 
HA: 
mCherry: 
HSP70: 3303
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "D HEK 293T cells expressing HA-tagged UBQLN2 and FLAG-tagged HSP70 (WT or ΔC) were incubated with 5 µg/mL A/O for 5 h. The cells were then subjected to immunoprecipitation assay using anti-FLAG antibody.",
    "ncbi_link": "FLAG: 
HA: 
HSP70: 3303
UBQLN2: 29978"
  },
  {
    "caption": "E HEK 293T cells expressing HA tagged UBQLN2-WT, ΔUBA or P497H) and FLAG-tagged HSP70 were incubated with 5 µg/mL A/O for 5 h. Immunoprecipitation assay were performed using UBQLN2 antibody.",
    "ncbi_link": "FLAG: 
HA: 
HSP70: 3303
UBQLN2: 29978"
  },
  {
    "caption": "G The quantification data of UBQLN2 recruitment to mitochondria after 5 µg/mL A/O treatment. HEK 293T cells were transfected with indicated siRNAs. The cells were re-transfected with HA-tagged UBQLN2-WT, mCherry-Parkin, along with BFP-mito, and treated with 5 µg/mL A/O for 5 h. The cells were subjected to immunofluorescent assay using anti-HA antibody. Data from three independent experiments were represented as means ± SD., Sixty cells were counted for each sample. **, p<0.01, one-way ANOVA.",
    "ncbi_link": "BFP: 
HA: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "A HEK 293T cells expressing mCherry-Parkin were pre-treated with proteasome inhibitor (20 µM MG132) for 12 h, and treated with 1 µg/mL A/O for 2 h. Then the cells were fractionated and proteins were immunoblotted for relative antibodies. B The level of Mfn2 (OMM protein), TOM20, COXIV and HSP60 was quantified and normalized relative to GAPDH, and was shown in A. The data from three independent experiments were presented as mean± SD., ns, not significantly different; **, p<0.01; ***, p<0.001, one-way ANOVA.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "HEK 293T cells were transfected with indicated siRNAs for 48 h. C The cells were re-transfected with mCherry-Parkin for 12 h and were pre-treated with or without 20 µM MG132 for 12 h and treated with1 µg/mL A/O for 2 h. The cell lysates were subjected to immunoblot with indicated antibodies. The data from three independent experiments were presented as mean± SD., ns, not significantly different; *, p<0.05; **, p<0.01, one-way ANOVA.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "HEK 293T cells were transfected with indicated siRNAs for 48 h. The cells were transfected with HA-tagged UBQLN2-WT or ∆379-462, along with mCherry-Parkin for 12 h. Then the cells were treated with 1 µg/mL A/O for 2 h. The cell lysates were subjected to immunoblot using indicated antibodies. G Relative densities from F were shown in G. The data from three independent experiments were presented as means ± SD., ns, not significantly different; *, p<0.05; **, p<0.01, one-way ANOVA.",
    "ncbi_link": "HA: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "HEK 293T cells were transfected with indicated siRNAs for 48 h. H The cells were re-transfected with HA-tagged UBQLN2-WT, along with mCherry-Parkin for 12 h. Then the cells were pretreated with 20 µM MG132 for 12 h and treated with 5 µg/mL A/O for 4 h. Mitochondria isolated from cell lysates were treated with or without 10 µg/mL proteinase K (Pro.K) and then were subjected to immunoblot with indicated antibodies. Mito: the isolated mitochondria; Mito (Pro.K): mitochondria after Pro.K treatment. COXIV level in \"Mito (Pro.K)\" group was quantified and normalized relative to HSP60 in \"Mito group\". The data from three independent experiments were presented as mean± SD., ** p<0.01, ***, p<0.001, one-way ANOVA.",
    "ncbi_link": "HA: 
mCherry: 
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "HEK 293T cells were transfected with indicated siRNAs for 48 h. I The cells were re-transfected with HA, HA-UBQLN2-WT or P497H, along with GFP-Parkin and FLAG-PHB2 for 20 h, and then were treated with or without 5 µg/mL A/O for 4 h. Images of situ PLA using rabbit anti-LC3B and mouse anti-FLAG antibodies. Blue: nuclei (DAPI); white dots: PLA positive puncta. Scale bar, 10 µm. J Over 500 cells were counted for each sample in I. The data from three independent experiments were presented as mean± SD., *, p<0.05; ** p<0.01, ***, p<0.001, one-way ANOVA.",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
PHB2: 11331
Parkin: 5071
UBQLN2: 29978"
  },
  {
    "caption": "A Mouse cortical neurons (DIV 7) were infected with lentivirus carrying mCherry-Parkin for 45 h, and then the neurons were treated with 5 µg/mL A/O for 5 h and subjected to immunofluorescent assay using anti-UBQLN2 (green) and anti-HSP60 (gray) antibodies. Scale bars, 10 µm. Lower panel were higher magnifications of the dashed box area. Scale bar, 2.5 µm.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "Mouse cortical neurons (DIV 7) were transfected with indicated siRNAs for 24 h. B The neurons were infected with lentivirus carrying mCherry-Parkin for 24 h and then were treated with 1 µg/mL A/O for 48 h. The neurons were stained with DAPI, anti-UBQLN2 (green) and anti-HSP60 (gray) antibodies and visualized. Scale bars, 10 µm. Yellow arrows indicate uncleared mitochondria.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "Mouse cortical neurons (DIV 7) were transfected with indicated siRNAs for 24 h. F The neurons were infected with lentivirus carrying mCherry-Parkin for 36 h and were treated with 100 ng/mL Antimycin A (Antimycin A alone, AA) and 1 µM DFP for 10 h. The neurons were subjected to immunofluorescent assay using anti-TOM20 (magenta) and anti-LAMP 2 (gray) antibodies. Scale bars, 10 µm. Right panel were higher magnifications of the dashed box area. Scale bars, 2.5 µm. Yellow arrows indicate the co-localization between mitochondria and lysosomes.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "Mouse cortical neurons (DIV 7) were transfected with indicated siRNAs for 24 h. H The neurons were infected with lentivirus carrying mCherry-Parkin for 24 h. Then, the neurons were treated with 100 ng/mL Antimycin A and 1 µM DFP for another 10 h and subjected to immunofluorescent assay using anti-MAP2 antibody. Scale bars, 10 µm. I, J The neurite length (I) and cell death (J) in more than 30 neurons were quantified from each group in H. The data from three independent experiments were presented as the means ± SD., *, p<0.05; ***, p<0.001, one-way ANOVA.",
    "ncbi_link": "mCherry: 
Parkin: 5071"
  },
  {
    "caption": "B HeLa cells stably expressing SEPT6-GFP were infected with S. flexneri AfaI for 4 h, harvested, and then tested with Co-IP. Empty vector and/or uninfected HeLa cells were used in parallel as control. GFP-trap magnetic agarose beads were used to isolate SEPT6-GFP from cells, and extracts were immunoblotted for SEPT6, GFP, SEPT7, or p62. The lysates were immunoblotted for GAPDH as control for cellular protein levels.",
    "ncbi_link": "SEPT6: 23157"
  },
  {
    "caption": "E HeLa cells were treated with control (CTRL), Drp1, or Mfn1 siRNA for 72 h. Whole cell lysates were immunoblotted for Drp1 or Mfn1 to show the efficiency of depletion. GAPDH was used as loading control. siRNA-treated cells were infected with S. flexneri for 4 h 40 min, then fixed for microscopy and stained for endogenous SEPT7 for quantitative confocal microscopy. Graph represents the mean % ± SEM of Shigella inside SEPT7 cages from at least 4 independent experiments per treatment. Student's t-test, ** = p <0.01; *** = p<0.001.",
    "ncbi_link": "Drp1: 10059
Mfn1: 55669"
  },
  {
    "caption": "A HeLa cells were treated with control (CTRL), SEPT7, or Drp1 siRNA for 72 h. Whole cell lysate of siRNA-treated cells were immunoblotted for GAPDH, SEPT7, or Drp1 to show the efficiency of siRNA depletion. GAPDH was used as loading control. siRNA-treated cells were labelled with MitoTracker Red CMXRos, and fixed for confocal microscopy. The scale bar represents 5 μm.",
    "ncbi_link": "Drp1: 10059
SEPT7: 989"
  },
  {
    "caption": "B HeLa cells were treated with control (CTRL), SEPT2, SEPT7, SEPT9, Drp1, or SEPT7+ Drp1 siRNA for 72 h, labelled with MitoTracker Red CMXRos, and fixed for quantitative confocal microscopy. Graph represents the distribution in length (μm; whiskers from min to max) of mitochondria in siRNA-treated cells from 3 independent experiments (analysis of at least 100 measurements per biological replicate). Student's t-test, *** = p<0.001.",
    "ncbi_link": "Drp1: 10059
SEPT2: 4735
SEPT7: 989
SEPT9: 10801"
  },
  {
    "caption": "C HeLa cells stably expressing SEPT6-GFP were harvested, and then tested with Co-IP. HeLa cells expressing GFP were used in parallel as control. GFP-trap magnetic agarose beads were used to isolate SEPT6-GFP from cells, and extracts were immunoblotted for Drp1, SEPT2, SEPT7, or GFP. The lysates were immunoblotted for GAPDH as control for cellular protein levels.",
    "ncbi_link": "SEPT6: 23157"
  },
  {
    "caption": "D HeLa cells were treated with control (CTRL) or SEPT7 siRNA for 72 h, and whole cell lysates were immunoblotted for SEPT7, Drp1, phosphorylated Drp1 (P-Drp1), or Mfn1. GAPDH was used as loading control. Graph represents the mean % ± SEM of the relative amount of Drp1, P-Drp1, Mfn1, or SEPT7 proteins quantified by densitometry from 4 independent experiments. Student's t-test, ns = non-significant; ** = p<0.01, *** = p<0.001.",
    "ncbi_link": "SEPT7: 989"
  },
  {
    "caption": "E HeLa cells were treated with control (CTRL) or SEPT7 siRNA for 72 h, labelled with MitoTracker Red CMXRos, then fixed and labelled for endogenous P-Drp1 for quantitative confocal microscopy. Representative images shown here. The scale bar represents 1 μm. The recruitment of P-Drp1 to mitochondria was significantly decreased as compared to control cells as measured by Pearson's correlation coefficient from at least 5 independent experiments (mean ± SEM, analysis of at least 250 cells per biological replicate). Student's t-test, * = p<0.05.",
    "ncbi_link": "SEPT7: 989"
  },
  {
    "caption": "F HeLa cells were treated with control (CTRL) or SEPT7 siRNA for 72 h, labelled with MitoTracker Red CMXRos, then fixed and labelled for endogenous Mfn1 for quantitative confocal microscopy. Representative images shown here. The scale bar represents 1 μm. The recruitment of Mfn1 to mitochondria was significantly increased as compared to control cells as measured by Pearson's correlation coefficient from at least 5 independent experiments (mean ± SEM, analysis of at least 250 cells per biological replicate). Student's t-test, * = p<0.05.",
    "ncbi_link": "SEPT7: 989"
  },
  {
    "caption": "A HeLa cells stably expressing SEPT6-GFP were treated with Drp1 siRNA for 72 h, transfected with mito-BFP 24 h, and then infected with S. flexneri-mCherry for 2 h for live confocal microscopy. Representative image shows interplay between two Shigella-septin cages and fused mitochondria. The scale bar represents 1 μm. See also Movie EV3.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "B HeLa cells were treated with Drp1 siRNA for 72 h, and then infected with x-light Shigella mCherry for 4 h 40 min for quantitative confocal microscopy. IPTG was added 30 min prior to fixation, and then samples were labelled with antibody for SEPT7. Graph represents mean % ± SEM of Shigella responding to IPTG outside (-) or inside (+) SEPT7 cages from 3 independent experiments. Student's t-test, *** = p<0.001.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "D HeLa cells were either kept uninfected as a control or infected with S. flexneri M90T or S. flexneri ΔIcsA for 4 h 40 min. Samples were labelled with MitoTracker Red CMXRos, and fixed for quantitative confocal microscopy. Boxplots show length of mitochondria (μm; whiskers from min to max) in uninfected cells (CTRL), surrounding S. flexneri M90T (+M90T) or S. flexneri ΔIcsA (+ΔIcsA) from 3 independent experiments (analysis of at least 250 measurements per biological replicate). Student's t-test; *** = p<0.001.",
    "ncbi_link": "IcsA: 876473"
  },
  {
    "caption": "Quantitative RT-PCR shows that Lpin1 expression is depleted in the skeletal muscles Gastrocnemius (GC) and Tibialis Anterior (TA), but not in White Adipose Tissue (WAT) from 3-month-old HSACre/+/Lpin1fEx2-3/fEx2-3 mice (HSA-Cre) compared to control mice. Expression levels are corrected for expression of the control gene Pinin and presented in the graph as fold change relative to control mice.",
    "ncbi_link": "Pinin: 
Cre: 2777477
Lpin1: 14245"
  },
  {
    "caption": "PAP1 and PAP2 activities were respectively substantially decreased and increased in TA, of HSA-Cre mice as compared to control mice, respectively (n = 6; *P<0.05).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Measurements of muscle/body weight ratio of GC and TA of 3-month-old HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Hematoxylin and Eosin (HE) staining of representative transverse sections of GC muscles from 3-month-old HSA-Cre and control mice. The black arrows indicate fibers with centrally located nuclei and yellow arrows indicate mononuclear cell infiltration. Scale bars: 40 μm",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Relative force measurements after normalization of absolute tetanic force to GC muscle weight from 3-month-old HSA-Cre and control male mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Phosphatidic Acid (PA) levels in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Phospholipidome in HSA-Cre and control GC muscles. Proportions of indicated phospholipid classes in total phospholipids are represented. PC; Phosphatidylcholine, PE; Phosphatidylethanolamine, PI; Phosphatidylinositol, PS; Phoshpatidylserine, PA; Phosphatidic Acid, PG; Phosphatidylglycerol.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Amounts of indicated phospholipid classes normalized by protein content in HSA-Cre and control GC muscles. (D) Total phospholipid (PL) amount normalized by protein content in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Distribution of the total carbon number in acyl chains of PC in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Distribution of the number of double bonds in acyl chains of PC in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Distribution of the total carbon number in acyl chains of PE in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Distribution of the number of double bonds in acyl chains of PE in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "HE, Oil Red O (ORO), Cytochrome c Oxidase (COX) and Succinate Deshydrogenase (SDH) staining of representative frozen sections of TA muscle from 3-month-old HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantification of triacylglycerol (TAG) levels in GC muscles from 3-month-old HSA-Cre and and control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Content of TAG assessed by MS in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Cholesterol, (E) Cholesteryl ester (CE), (F) DAG was assessed by MS in HSA-Cre and control GC muscles.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantitative RT-PCR detection of the level of expression of Fatty acid synthase (Fasn), ATP citrate lyase (Acly), Thyroid hormone-inducible hepatic protein 1 (Thrsp1), Angiopoietin-like protein 4/ fast-induced adipose factor (ANGPTL4/Fiaf), Insulin-induced gene 1 (Insig1) and Peroxisome proliferator-activated receptor gamma (PPARγ) in TA from 3-month-old HSA-Cre and control mice. Expression levels are corrected for expression of the control gene Pinin and presented in the graph as fold change relative to control mice.",
    "ncbi_link": "Pinin: 
Acly: 104112
ATP citrate lyase: 104112
Angiopoietin-like protein 4: 57875
ANGPTL4: 57875
fast-induced adipose factor: 57875
Fiaf: 57875
Cre: 2777477
Fasn: 14104
Fatty acid synthase: 14104
Insig1: 231070
Insulin-induced gene 1: 231070
Peroxisome proliferator-activated receptor gamma: 19016
PPARγ: 19016
Thrsp1: 21835
Thyroid hormone-inducible hepatic protein 1: 21835"
  },
  {
    "caption": "Immunoblot analysis of Fasn in TA muscle of 3-month-old HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantitative RT-PCR measurement of Carnitine palmitoyltransferase 1B (Cpt1b) and Medium-chain acyl-CoA dehydrogenase (Mcad) in TA from 3-month-old HSA-Cre and control mice.",
    "ncbi_link": "Mcad: 11364
Medium-chain acyl-CoA dehydrogenase: 11364
Cpt1b: 12895
Carnitine palmitoyltransferase 1B: 12895
Cre: 2777477"
  },
  {
    "caption": "Immunoblot analysis of full length and N-terminal SREBP1c and SREBP2 protein levels in GC muscle of 4-month-old HSA-Cre and control mice (n=7-4). The ratio of the densitometric assay of the N-term and Full length forms is presented.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Metabolomics profile of GC muscle of 4-month-old HSA-Cre and control mice presented as heatmap visualization and hierarchical clustering analysis of compounds",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Fold change of phospholipid precursors in GC muscles of 4-month-old HSA-Cre and control mice measured by liquid-chromatography (LC) tandem mass spectrometry (MS/MS) (n=7-4, *P<0.05).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Fold change of Lactate/Pyruvate, Pyruvate/AcetylCoA, Pyruvate/Citrate, ATP/AMP, and ATP/ADP ratios in GC muscles of 4 month-old HSA-Cre and control mice (n=7-4, *P<0.05).",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "UPR activation was analysed by immunoblotting with indicated antibodies in GC muscles of 4-month-old HSA-Cre and control mice (n=7-4). Quantification by densitometric analyses of Fgf21, Bip, sXbp1 Atf6 cleaved form, p-Eif2a and Chop protein levels is presented as a graph. Data are normalized to Gapdh and expressed as a fold change relative to the control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantitative RT-PCR measurement of Fgf21, Gdf15, Bip/Grp78, hsp90b1, and Edem1 in GC muscles from 4-month-old HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477
Edem1: 192193
Fgf21: 56636
Gdf15: 23886
hsp90b1: 22027
Bip: 14828
Grp78: 14828"
  },
  {
    "caption": "EM analysis of EDL fibers of HSA-Cre mice revealed the presence of areas in which the non-junctional SR is more vesiculated and fragmented compared to control (black arrows). Remodeling of the SR is also accompanied by modification in the positioning of mitochondria (white arrows). A representative Calcium Release Unit (CRU) is indicated (empty arrow). Scale bars: 0.50 μm.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "The relative mtDNA copy number was determined by the ratio of mitochondrial DNA-encoded Cytochrome B (CytB) and nuclear-encoded NADH dehydrogenase (ubiquinone) flavoprotein 1 (Ndufv1) genes in GC and TA from HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477
CytB: 17711
Cytochrome B: 17711
Ndufv1: 17995
NADH dehydrogenase (ubiquinone) flavoprotein 1: 17995"
  },
  {
    "caption": "Mitochondria-encoded gene and Nuclear-encoded gene expression levels by quantitative RT-PCR in GC muscles from 4-month-old HSA-Cre and control mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Electron micrographs of HSA-Cre EDL muscles of 3-month-old mice showed that mitochondria are almost exclusively positioned at the two sides of Z lines in EDL fibers from control mice (black arrows). On the other hand, in Lipin1 deficient EDL fibers mitochondria are more often clustered and display electron-dense contact sites (white arrows). Scale bars: 0.20 μm.",
    "ncbi_link": "Cre: 2777477
Lipin1: 14245"
  },
  {
    "caption": "Ultrastructural analysis of HSA-Cre EDL muscles revealed the presence of numerous autophagic vacuoles of different morphologies (autophagosomes and lysosomes, black arrows; multilamellar bodies, white arrow) containing amorphous material and possibly degraded mitochondria (M). Scale bars: 0.50 μm",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Representative immunoblots from protein extract of GC muscles of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice, with the indicated antibodies.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantitative RT-PCR measurement of Fgf21 and GDF15 expression in GC muscle of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice.",
    "ncbi_link": "Cre: 2777477
Fgf21: 56636
GDF15: 23886"
  },
  {
    "caption": "Histological analysis of TA muscles of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice by Oil Red O staining to detect the neutral lipids. Scale bars: 40 μm.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "TAG level measurement in GC muscles of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "In vivo force measurements performed on GC muscles of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Representative staining of IgG positive fibers on frozen sections of TA of 6-month-old control, HSA-Cre untreated and HSA-Cre TUDCA-treated mice. The sections were stained with a secondary fluorescent anti-mouse IgG antibody. Quantification of the number of necrotic fibers over the total number of fibers.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Representative immunoblots from protein extract of GC muscles of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice, with the indicated antibodies.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Quantitative RT-PCR measurement of Fgf21 and GDF15 expression in GC muscle of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice.",
    "ncbi_link": "Cre: 2777477
Fgf21: 56636
GDF15: 23886"
  },
  {
    "caption": "Histological analysis of TA muscles of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice by Oil Red O staining to detect the neutral lipids.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "TAG level measurement in GC muscles of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "In vivo force measurements performed on GC muscles of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "Representative staining of IgG positive fibers on frozen sections of TA of 4-month-old control, HSA-Cre untreated and HSA-Cre Bezafibrate-treated mice. The sections were stained with a secondary fluorescent anti-mouse IgG antibody. Quantification of the number of necrotic fibers over the total number of fibers.",
    "ncbi_link": "Cre: 2777477"
  },
  {
    "caption": "A-D, Single (A), double (B), triple (C), and quadruple (D) cysteine mutant NDP52  plasmids were generated and transfected into HeLa PentaKO cells. Cells were treated with 20 µM  PR-619  for 10 min and analysed by immunoblotting  for NDP52  in either reducing  or non-reducing conditions. The constructs highlighted in red were subjected to the next round of Cys-Ala screen or further analyses.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "A, B, Fluorescence microscopy images (A) and quantification (B) of mitophagy  of HeLa  wild-type (WT),  PentaKO + empty vector, PentaKO + NDP52  WT or NDP52  C18,153,163,321S (Mut) cells, stably expressing YFP-Parkin    and mt-mKeima    were pre-treated with or without MitoQ for 22 h and treated with 4 µM / 10 µM AO for the indicated times. Data information Data are mean ± s.e.m. (B or displayed as cell popular violin plots (B). P values were calculated by one-way ANOVA followed by Sidak test on three independent experiments (B *, p<0.05; **, p<0.01; ***, p<0.001; §, p<0.05, §§§, p<0.001 (relative to MitoQ-untreated condition); ns (non-significant). Scale bars: 20 μm (A",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "C, HeLa PentaKO + NDP52  WT or NDP52  Mut cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 4 µM / 10 µM AO for 2 h in the absence or presence of 10 μM MG132  (MG) and 400 nM Baf, followed by a mitochondrial  fractionation and immunoblotting  for NDP52  in non-reducing conditions. The mitochondrial  protein UQCRC2  was used as a loading control. Data information: #, non-specific band or a post-translational modification.",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "D, HeLa PentaKO + NDP52  WT cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 1 mM DFP  for 24 h (D), or pre-treated with 500 nM MitoQ  for 22 h and treated with 4 µM / 10 µM AO for 2 h (D Cells were then analysed by MitoSOX staining  (D) Data information: #, Data are mean ± s.e.m. D) P values were calculated by one-way ANOVA followed by Sidak test on three independent experiments D). *, p<0.05; **, p<0.01; ***, p<0.001; §, p<0.05, §§§, p<0.001 (relative to MitoQ-untreated condition); ns (non-significant). Scale bars: 20 μm D).",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "E, HeLa PentaKO + NDP52  WT cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 500 nM MitoQ  for 22 h and treated with 4 µM / 10 µM AO for 2 h E) in the presence or absence of 400 nM Baf  (E). immunoblotting  for NDP52  (E). Data information: #, non-specific band or a post-translational modification.",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "A, Fluorescence microscopy  images and quantification of mitophagy  in HeLa PentaKO + NDP52  WT cells stably expressing YFP-Parkin    and mt-mKeima    were treated with 4 µM rotenone  (R), 4 µM A, 10 µM O, or the combination of RO or AO for 3h. Data information Data are mean ± s.e.m. (A or displayed as cell popular violin plots (A, P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on at least three independent experiments as indicated (A, *, p<0.05; **, p<0.01; ***, p<0.001; ns (non-significant). Scale bars: 20 μm (A",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "B, Fluorescence microscopy  images and quantification of MitoSOX staining  in HeLa PentaKO + NDP52  WT cells in the same conditions as (A). Data information Data are mean ± s.e.m. B, or displayed as cell popular violin plots B, P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on at least three independent experiments as indicated B, *, p<0.05; **, p<0.01; ***, p<0.001; ns (non-significant). Scale bars: 20 μm B,",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT cells stably expressing YFP-Parkin  and mt-mKeima  (C, were pre-treated with or without 10 µM S1QEL  or 20 µM S3QEL  for 30 min and treated with AO for 2 h or with RO for 3 h, followed by mitophagy  measurement (C) Data information Data are mean ± s.e.m. C, or displayed as cell popular violin plots C, P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on at least three independent experiments as indicated C, *, p<0.05; **, p<0.01; ***, p<0.001; ns (non-significant). Scale bars: 20 μm",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT cells (D) were pre-treated with or without 10 µM S1QEL  or 20 µM S3QEL  for 30 min and treated with AO for 2 h or with RO for 3 h, followed by MitoSOX staining  (D) Data information Data are mean ± s.e.m. P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on at least three independent experiments as indicated *, p<0.05; **, p<0.01; ***, p<0.001; ns (non-significant). Scale bars: 20 μm , D",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT cells stably expressing YFP-Parkin  and mt-mKeima  E) were pre-treated with or without 10 µM S1QEL  or 20 µM S3QEL  for 30 min and treated with AO for 2 h or with RO for 3 h, followed by immunoblotting  for NDP52  in non-reducing conditions (E). Data information: #, non-specific band or a post-translational modification.",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "F, HeLa  PentaKO + NDP52  WT stably expressing YFP-Parkin  and mt-mKeima  were pre-treated with or without 10 mM DTT  for 30 min and treated with AO for 2 h followed by mitophagy  measurements (F) Data information Data are mean ± s.e.m. F) or displayed as cell popular violin plots F). P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on at least three independent experiments as indicated F). *, p<0.05; **, p<0.01; ***, p<0.001; ns (non-significant). Scale bars: 20 μm F).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "G, HeLa PentaKO + NDP52  WT stably expressing YFP-Parkin  and mt-mKeima  were pre-treated with or without 10 mM DTT  for 30 min and treated with AO for 2 h followed by immunoblotting  for NDP52 in non-reducing conditions (G). Data information: #, non-specific band or a  post-translational modification.",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT or NDP52  Mut cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 4 µM / 10 µM AO for 2 h in the presence or absence of 400 nM Baf, followed by immunofluorescence  analyses (A) The number of foci of the indicated proteins colocalised  with NDP52, or foci of NDP52 colocalised  with Parkin, was quantified. Data information: Data are mean ± s.e.m. (A, P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on three independent experiments (A *, p<0.05; **, p<0.01; ***, p<0.001; §§, p<0.01; §§§, p<0.001 ns (non-significant). Scale bars: 20 μm (A,",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT or NDP52  Mut cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 4 µM / 10 µM AO for 2 h in the presence or absence of 400 nM Baf, followed by immunoblotting  for LC3   and NDP52  in mitochondrial  fraction (B) or  whole cell lysate (C) in reducing conditions Data information: Data are mean ± s.e.m. B, C, P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on three independent experiments B, C *, p<0.05; **, p<0.01; ***, p<0.001; §§, p<0.01; §§§, p<0.001 ns (non-significant).",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "HeLa PentaKO + NDP52  WT or NDP52  Mut cells stably expressing YFP-Parkin  and mt-mKeima  were treated with 4 µM / 10 µM AO for 2 h in the presence or absence of 400 nM Baf, followed by co-immunoprecipitation  assay to analyse the interaction  of NDP52  with FIP200, ULK1  and ATG13  (D). Data information: Data are mean ± s.e.m. P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on three independent experiments D, *, p<0.05; **, p<0.01; ***, p<0.001; §§, p<0.01; §§§, p<0.001 ns (non-significant).",
    "ncbi_link": "mKeima: 
YFP: 
NDP52: 10241
Parkin: 5071"
  },
  {
    "caption": "E, MEFs  stably expressing YFP-Parkin, mt-mKeima  and empty, human NDP52  (hNDP52) WT or hNDP52 Mut were pre-treated with or without 500 nM MitoQ  for 21 h and treated with AO for 3 h followed by mitophagy  measurement. Data information: Data are mean ± s.e.m. E) or displayed as cell popular violin plots (E). P values were calculated by one-way ANOVA followed by Sidak test (for multiple groups) or unpaired two-tailed Student's t-test (for two groups) on three independent experiments E). *, p<0.05; **, p<0.01; ***, p<0.001; §§, p<0.01; §§§, p<0.001 (relative to MitoQ-untreated condition); ns (non-significant). Scale bars: 20 μm E).",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "B. HoxB8 macrophages  were treated with the indicated dilutions of  GM-CSF using supernatants from GM-CSF  expressing cells. Shown are ELISA analysis of  IL-1β secretion in supernatants and  western blots  indicating IL-1β  expression in lysates.. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "C. HoxB8 macrophages  of the indicated genotypes were treated as indicated with 60ng/mL UP-LPS, 1%  GM-CSF containing supernatant (approximately 2ng/mL GM-CSF), 40µM WEHD.FMK, 0,5µM  CRT-0066101  for 16 hours, 5µM nigericin was added for the last hour. Supernatants were analysed by ELISA  for IL-1β. Inlay panels show western blots for levels of IL-1β  expression in the indicated knockouts. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "D. HoxB8 cells were treated with 60ng/mL of UP-LPS, 1%  GM-CSF supernatant, 50mM KCl, and 5µM nigericin  as indicated for 16 hours before supernatants were analysed for  IL-1β by ELISA. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "A. BMDMM  (left panel) and HoxB8 macrophages  (right panel) were treated as indicated with either LPS  or LPS+ GM-CSF. Cells were harvested and proteins extracted and analysed by western blot for levels of NRF2. Shown is the densitometric  quantification of Nrf2  protein level from three independent experiments. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "B. HoxB8 macrophages  were treated as in A. and levels of  IL-1β in the supernatant were analysed by ELISA  Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "C. HoxB8 macrophages were treated for 12 hours with LPS  or LPS+GM-CSF and RNA extracted and analysed by qPCR  for the indicated targets. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "D. Wild type and Tnf-/- HoxB8  cells were treated as indicated. Cells were harvested and proteins extracted and analysed by western blot for levels of NRF2  and HMOX1. For wild type cells,  MitoTEMPO (50µM) was also added as indicated. Shown are the densitometric  quantifications of NRF2  and HMOX1  protein levels of three independent experiments (right panel). Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416
Tnf: 21926"
  },
  {
    "caption": "E. HoxB8  cells of the indicated genotypes were treated with LPS  for 8 hours followed by staining  with mitoSOX red. The fluorescent signal was analyzed using flow cytometry. Shown are average geometric mean fluorescence intensity of mitoSOX red. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "F. Tnf-/- HoxB8 macrophages  were treated with LPS  with or without 50ng/ml recombinant TNF  for 16 hours. Cells were harvested and proteins extracted and analysed by western blot  for levels of NRF2  and HMOX1  (upper panel). Shown are the densitometric  quantifications of indicated protein levels of three independent experiments (lower panel). Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. For the western blot quantification, significance was calculated using unpaired t-test. p values are shown.",
    "ncbi_link": "HoxB8: 15416
Tnf: 21926"
  },
  {
    "caption": "A. HoxB8 macrophages  were seeded in an 8-well Ibidi chamber and treated as indicated for 12 hours. Cells were fixed and stained  for ASC  (Red) and with DAPI  (blue). For nigericin  treatments nigericin  was added for only 30 minutes. Example cells containing ASC  Specks are shown with white arrows. Scale bars represent 50µM. Data information: Microscopy  pictures are representative images from 3 biological replicates.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "B. HoxB8  cells were treated as indicated with LPS  or LPS+GM-CSF. The cross linker DSS  was added to the cells as described in methods. Samples were analysed by western blot  for ASC oligomerization. Black vertical lines indicate that non-relevant lanes were removed during figure preparation but samples were run on the same gel. Data information: westerns  are representative images from 3 biological replicates.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "C. Wild type and caspase-1-/- HoxB8 macrophages were treated as indicated for 16 hours. Cell lysates were made and analysed by  western blot for levels of  caspase-1  and gasdermin D cleavage. Data information: westerns  are representative images from 3 biological replicates.",
    "ncbi_link": "caspase-1: 12362
HoxB8: 15416"
  },
  {
    "caption": "D. HoxB8 macrophages  were treated as indicated with LPS  or LPS+GM-CSF for 12 hours. Cells were lysed and NLRP3  was  immune precipitated using a magnetic bead coupled antibody. As a negative control, beads without NLRP3  antibody were used. Beads were boiled and analysed for recruitment of NLRP3, and caspase-1. * indicates light chain from the antibody. Molecular weight markers shown in middle of NLRP3  blot were embedded in image using Chemostar imaging software (INTAS) at time of image acquisition. Data information: westerns  are representative images from 3 biological replicates.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "E. HoxB8 macrophages  were incubated with combinations of LPS, GM-CSF, nigericin  +/- Z-VAD.FMK as indicated. Proteins were extracted and analysed by western blot  for caspase-1 processing. Data information: westerns  are representative images from 3 biological replicates.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "F. HoxB8 macrophages  were seeded in a 96 well microplate and co-treated with either 10µM or 50µM  z-VAD with LPS+GM-CSF  for 16 hours. Then 100nM of Sytox Green  was added to the cells. The number of sytox green+ cells per image was quantified. Data information: Significance was calculated using one way ANOVA with multiple comparisons. Every dot represents one biological replicate. P values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "A. HoxB8 macrophages  were treated for 16 hours with LPS  +/- GM-CSF as indicated. Proteins were extracted and analysed for levels of  IL-1β by western blot.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "B. HoxB8 macrophages  were treated with LPS  or LPS+GM-CSF as indicated for 16 hours. Cells were lysed in buffer containing FLAG  tagged K63 TUBE  and K63 ubiquitylated  proteins were precipitated using anti FLAG pull down. Pulled down  proteins were analysed for  IL-1β and ubiquitin   by western blot.",
    "ncbi_link": "FLAG: 
HoxB8: 15416"
  },
  {
    "caption": "C. IL-1β-/- hoxB8 macrophages  were infected with lentivirus  expressing IL-1β-FLAG-6xHis or the indicated mutants from the  IL-1β promoter. Cells were treated as indicated with LPS or LPS+GM-CSF or LPS+Nigericin and levels of secreted  IL-1β were analysed by ELISA  (top panel). GM-CSF treated cells were also lysed in urea buffer and nickel  NTA affinity pull down was performed. Nickel  NTA pull down was also performed on supernatants (bottom panel). Pulled down proteins form the His tag pull down were analysed for the presence of  IL-1β by western blot. Molecular weight markers shown in middle of blot  were embedded in image using Chemostar imaging software (INTAS) at time of image acquisition. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "FLAG: 
His: 
hoxB8: 15416
IL-1β: 16176"
  },
  {
    "caption": "D. HoxB8 macrophages  were treated as in A with addition of 50µM mitoTEMPO or 10mM NAC as indicated. Proteins were extracted and analysed for  IL-1β by  western blot.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "E. Wild type and TNF-/- HoxB8 macrophages  were treated as indicated with LPS  or LPS+GM-CSF. Proteins were extracted and analysed for  IL-1β by  western blot. Black vertical lines indicate that non-relevant lanes were removed during figure preparation but samples were run on the same gel.",
    "ncbi_link": "HoxB8: 15416
TNF: 21926"
  },
  {
    "caption": "F. HoxB8 macrophages  were treated as in A but with the addition of 25µM Punicalagin  throughout the 16 hour time course. Proteins were extracted and analysed by western blot (left panel). Supernatants were also analysed by ELISA for secreted IL-1β (right panel). Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "A. Wild type and GsdmD-/- HoxB8 macrophages  were treated as indicated for 16 hours. Supernatants were analyzed for IL-1β secretion by ELISA. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "GsdmD: 69146
HoxB8: 15416"
  },
  {
    "caption": "B. HoxB8 macrophages  were seeded in an 8-well Ibidi chamber and treated for 14 hours with LPS  and  GM-CSF. Cells were fixed and stained  for GasderminD  (green),  IL-1β (red) and DAPI (blue). Images were taken at the Zeiss LSM880 Confocal microscope Data information: shown. Microscopy  pictures are representative images from 3 biological replicates. Scale bars in microscopy  images represent 10µM.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "C. HoxB8 macrophages were co-stimulated with three different PEG  3mM for 16 hours as indicated. Supernatants were analyzed for IL-1β secretion by ELISA. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "D. HoxB8 macrophages  were seeded in 96 well microplate and treated as indicated. Before treatment, sytox green was added and cells were imaged in an incucyte incubator microscope  every hour for 16 hours. Shown is the sytox green signal normalized to the total cell area. Data information: n≥ 3 biological replicates (every dot represents one biological replicate). For all panels, error bars are SEM. Significance was calculated using one way ANOVA with multiple comparisons, or two-way ANOVA to compare across genotypes. p values are shown.",
    "ncbi_link": "HoxB8: 15416"
  },
  {
    "caption": "E. Wild type and GsdmD-/- HoxB8 macrophages were treated as indicated for 16 hours. Proteins were extracted and analysed for  IL-1β ubiquitination  by western blot. Data information: westerns  are representative images from 3 biological replicates.",
    "ncbi_link": "GsdmD: 69146
HoxB8: 15416"
  },
  {
    "caption": "(D) Using the dual color labeling system (esg-Gal4>UASp-FRT-H3-eGFP-FRT-H3-mCherry), old and new H3   distribution in prophase  and prometaphase ISCs  shows large, separable domains of H3-eGFP  (old) and H3-mCherry  (new). Note: all figure panels in this work are maximum intensity projection images to show signals from all Z-stacks. (E) Using the UASp-FRT-histone-eGFP-T2A-histone-mCherry-PolyA  transgene that co-expresses H3-eGFP    and H3-mCherry, significant overlap between the two signals were detected in ISCs  during prophase  and prometaphase. (F) Quantification of the colocalization  between old and new H3, as well as between the co-expressed eGFP- and mCherry-tagged H3    in prophase  and prometaphase ISCs. Pearson's correlation coefficients were measured, where 1 represents complete colocalization  and 0 stands for no colocalization. Old and new H3   showed significantly less colocalization  (Pearson's correlation coefficient for H3   = 0.44 + 0.02, n = 81 ISCs) when compared to the co-expressed eGFP- and mCherry-tagged H3   (Pearson's correlation coefficient for H3  co-expressed = 0.86 + 0.01, n = 19 ISCs). Individual data points and mean values are shown. Error bars represent SEM. **** p < 0.0001; unpaired t test to compare two individual datasets to each other. Data information: n for individual ISCs. Scale bar in (D), (E): 5 µm.",
    "ncbi_link": "eGFP: 
histone: 
mCherry: 
esg: 34903
Gal4: 855828
H3: 3771723"
  },
  {
    "caption": "(A) Old and new H4   distribution in prophase  and prometaphase ISCs  (esg-Gal4>UASp-FRT-H4-eGFP-FRT-H4-mCherry). Separable domains of H4-eGFP  (old) and H4-mCherry  (new) were observed (B) Old and new H2A   distribution in prophase  and prometaphase ISCs  (esg-Gal4>UASp-FRT-H2A-eGFP-FRT-H2A-mCherry), showing largely overlapping signals between H2A-eGFP  (old) and H2A-mCherry  (new). Data information: n for individual ISCs. Scale bar in (A), (B) 5 µm.",
    "ncbi_link": "eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
H2A: 3772345
H4: 318846"
  },
  {
    "caption": "(A) Old and new H3   distribution in a post-mitotic pair of cells with asymmetric Dl-nLacZ   labeling, showing that H3-eGFP  (old) is asymmetrically   inherited by the Delta-high cell, while H3-mCherry  (new) is enriched in the Delta-low cell (esg-Gal4>UASp-FRT-H3-eGFP-FRT-H3-mCherry). (B) Old and new H3   distribution in a post-mitotic pair of cells with symmetric Dl-nLacZ  labeling, showing that both H3-eGFP  (old) and H3-mCherry  (new) are more symmetrically  distributed between the two cells. Scale bar in (A), (B), 5 µm; asterisk, ISC  side.",
    "ncbi_link": "Dl-nLacZ: 
eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
H3: 3771723"
  },
  {
    "caption": "(E) Old and new H4   distribution in a post-mitotic pair of cells with asymmetric Dl-nLacZ   labeling, showing that H4-eGFP  (old) is asymmetrically  inherited by the Delta-high cell, while H4-mCherry  (new) is enriched toward the Delta-low cell (esg-Gal4>UASp-FRT-H4-eGFP-FRT-H4-mCherry). (F) Old and new H4   distribution in a post-mitotic pair with symmetric Dl-nLacZ  labeling, showing that H4-eGFP  (old) and H4-mCherry  (new) are symmetrically  distributed between the two cellss. Scale bar in (E), (F), 5 µm; asterisk, ISC  side.",
    "ncbi_link": "Dl-nLacZ: 
eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
H4: 318846"
  },
  {
    "caption": "(I) Old and new H2A   distribution in a post-mitotic pair of cells with asymmetric Dl-nLacZ   labeling, showing that H2A-eGFP  (old) and H2A-mCherry (new) are symmetrically  inherited by the two cells (esg-Gal4>UASp-FRT-H2A-eGFP-FRT-H2A-mCherry). (J) Old and new H2A   distribution in a post-mitotic pair of cells with symmetric Dl-nLacZ  labeling, showing that H2A-eGFP  (old) and H2A-mCherry (new) are symmetrically  distributed between the two cells. Scale bar in (I), (J), 5 µm; asterisk, ISC  side.",
    "ncbi_link": "Dl-nLacZ: 
eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
H2A: 3772345"
  },
  {
    "caption": "(M) The ISC-specific combination of drivers esg-Gal4, Su(H)-Gal80  drive H3   transgene [esg-Gal4, Su(H)-Gal80>UASp-FRT-H3-eGFP-FRT-H3-mCherry] with  heat shock treatment and recovery (see Materials and Methods) in a Delta-asymmetric  pair of cells. Old and new H3   distribution in a post-mitotic pair of cells with asymmetric Dl-nLacZ   labeling, showing that H3-eGFP  (old) is asymmetrically  inherited by the Delta-high cell, while H3-mCherry  (new) is enriched in the Delta-low cell. (N) ISC  specific drivers express the H3   transgene in a Delta-symmetric  pair of cells. Old and new H3   distribution in a post-mitotic pair of cells with symmetric Dl-nLacZ  labeling, showing that both H3-eGFP  (old) and H3-mCherry  (new) are more symmetrically  distributed between the two cells. Scale bar in (M), and (N): 5 µm; asterisk, ISC  side.",
    "ncbi_link": "Dl-nLacZ: 
eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
Gal80: 854954
H3: 3771723
Su(H): 34881"
  },
  {
    "caption": "(A) Old and new H3T3A  distribution in prophase ISC, showing separable domains between H3T3A-GFP   (old) and H3T3A-mKO  (new) (esg-Gal4>UASp-FRT-H3T3A-eGFP-FRT-H3T3A-mCherry). Data information: Scale bar in (A), (C), (E), (F): 5 µm,",
    "ncbi_link": "eGFP: 
mCherry: 
esg: 34903
Gal4: 855828
H3: 3771723"
  },
  {
    "caption": "(E) In a post-mitotic pair of cells with comparable  Dl-nLacZ, both H3T3A-GFP  (old) and H3T3A-mKO  (new) are symmetrically  distributed between the two cells. (F) In a post-mitotic pair of cells with asymmetric Dl-nLacZ expression, H3T3A-GFP  (old) is enriched in the Delta-high cell, while H3T3A-mKO  (new) is more toward the Delta-low cell. Data information: Scale bar in (E), (F): 5 µm, asterisk, ISC  side.",
    "ncbi_link": "Dl-nLacZ: "
  },
  {
    "caption": "(H) Distribution of the  Dl-nLacZ-positive (magenta) cells in an H3-expressing midgut, which are well spaced and interspersed within the  intestinal epithelium. (I) Distribution of the Dl-nLacZ-positive (magenta) cells in an H3T3A-expressing midgut, which are unevenly distributed in clusters with two or more Delta-positive cells. DAPI: white in (H-I). Data information: Scale bar in (H) and (I): 50 µm",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(K) Percentages of clusters with 1-, 2-, or >3-Delta-positive cell clusters for H3-expressing midguts   (avg. percentage of 1-Dl+ cells = 87.7% + 1.1%, avg. percentage of 2-Dl+ cells = 11.9% + 0.9%, avg. percentage of >3-Dl+ cells = 0.4% + 0.2%, N = 4 midguts, n = 1,482 clusters) and H3T3A-expressing midguts  (avg. percentage of 1-Dl+ cells = 68.2% + 1.2%, avg. percentage of 2-Dl+ cells = 28.5% + 0.9%, avg. percentage of >3-Dl+ cells = 3.3% + 0.4%, N = 5 midguts, n = 1,862 clusters). Bars represent mean proportions of cell clusters with 1, 2, or 3+ Dl+ cells out of all cell clusters counted. Error bars represent SEM. Comparing H3-expressing midguts  with H3T3A-expressing midguts, there was a statistically significant difference in the distributions of Delta-positive cells per cluster, determined by a Chi-Square test (X2(2, n = 1862) = 908.75, **** p < 0.0001). As shown, there are significant increases in 2 and >3-Delta-positive cells per cluster in the H3T3A-expressing intestines  when compared to the H3-expressing intestines.",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(L) Percentages of single Delta-positive cells out of total Delta-positive cells for H3-expressing midguts  (avg. single Dl+ cells = 77.9% + 1.9%, N = 4 midguts, n = 1,674 Dl+ cells) and H3T3A-expressing midguts  (avg. single Dl+ cells = 50.4% + 1.5%, N = 5 midguts, n = 2,522 Dl+ cells). Bars represent mean proportion of single Dl+ ISCs  out of all ISCs  counted. Error bars represent SEM. There are fewer single Delta-positive cells in H3T3A-expressing midguts  compared to H3-expressing midguts  (two sample t test, *** p < 0.001).",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(M) Comparison of the  mitotic index in H3-expressing (N = 8 midguts) and  H3T3A-expressing (N = 8 midguts) midguts. Total number of mitotic ISCs  were quantified per midgut  by the presence of H3S10 phosphorylation  mark. H3T3A-expressing midguts had a significantly higher mitotic index  when compared to H3-expressing midguts  (two sample t test, * p < 0.05). Bars represent mean number of mitotic  cells per midgut. Error bars represent SEM.",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(A) A view of the midgut  of an UAS-H3-mCherry  transgene driven by esg-Gal4, Su(H)-Gal80, tub-Gal80ts at the Gal80ts permissive temperature  (18°C), showing no expression  of the histone  transgene or the UAS-eYFP   reporter that marks ISCs. (B) A view of the midgut  of an UAS-H3-mCherry  transgene driven by esg-Gal4, SuH-Gal80, tub-Gal80ts at the  Gal80ts restrictive temperature  (29°C), showing expression  of the H3-mCherry  transgene (red) and the UAS-eYFP  reporter (green). (C) A view of the midgut  of an UAS-H3T3A-mCherry  transgene driven by esg-Gal4, SuH-Gal80, tub-Gal80ts at the Gal80ts permissive temperature  (18°C), showing no expression  of the histone  transgene or the UAS-eYFP  reporter. (D) A view of the midgut  of an UAS-H3T3A-mCherry  transgene driven by esg-Gal4, SuH-Gal80, tub-Gal80ts at the Gal80ts restrictive temperature  (29°C), showing expression  of the H3T3A-mCherry  transgene (red) and the UAS-eYFP  reporter (green). Data information: Scale bars in (A), (B), (C), and (D): 50 µm",
    "ncbi_link": "mCherry: 
esg: 34903
Gal4: 855828
Gal80: 854954
H3: 3771723
Su(H): 34881
SuH: 34881
tub: 40554"
  },
  {
    "caption": "(I) Comparison of the mitotic index  in H3-expressing (N = 11 midguts) and H3T3A-expressing (N = 11 midguts) midguts. Total number of mitotic ISCs  were quantified per midgut  by the presence of H3S10 phosphorylation  mark. Bars represent mean number of mitotic  cells per midgut. Error bars represent SEM. H3T3A-expressing midguts  had a significantly higher mitotic index when compared to H3-expressing midguts  (two sample t test, * p < 0.05).",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(J) Qualitative analysis of midgut  phenotypes. No phenotype is called when the ISCs  appear normally distributed based on eYFP  reporter signal. A mild phenotype is called when there is a small region of eYFP-positive cells clustered within a region, showing mild disorganization. A strong phenotype is called when there is a large region of eYFP-positive cells clustered, showing significant disorganization. (K) Percentage of H3- expressing midguts  (N = 11 midguts) and H3T3A- expressing midguts  (N = 11 midguts) with no phenotype, a mild phenotype, or a strong phenotype. Data information: Scale bars in (J): 500 µm.",
    "ncbi_link": "H3: 3771723"
  },
  {
    "caption": "(A) A view of the midgut  of an UAS-H3-mCherry  transgene driven by esg-Gal4, SuH-Gal80, tub-Gal80ts at the Gal80ts restrictive temperature (29°C), showing expression  of the H3-mCherry  transgene (grey) and the UAS-eYFP  reporter (green) from the driver as well as expression  of the Su(H)-LacZ  reporter line (magenta). eYFP  and Su(H)-LacZ  signals are organized and separable. (B) A view of the midgut  of an UAS-H3T3A-mCherry  transgene driven by esg-Gal4, SuH-Gal80, tub-Gal80ts at the Gal80ts restrictive temperature (29°C), showing expression  of the H3T3A-mCherry  transgene (grey) and the UAS-eYFP  reporter (green) from the driver as well as expression  of the Su(H)-LacZ  reporter line (magenta). eYFP  and  Su(H)-LacZ  signals are disorganized and overlapping. Data information: Scale bars in (A) and (B): 50 µm.",
    "ncbi_link": "mCherry: 
esg: 34903
Gal4: 855828
Gal80: 854954
H3: 3771723
SuH: 34881
tub: 40554"
  },
  {
    "caption": "(I) Wild-type and Cd22-/- primary B cells were treated with 5 µg/mL anti-kappa antibody or 1 µM LatA and intracellular calcium flux was measured by flow cytometry.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(J) Wild-type and Cd22Y2,5,6F primary B cells were treated with 5 µg/mL anti-kappa antibody or 1 µM LatA and intracellular calcium flux was measured by flow cytometry.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(K and L) Wild-type, Cd22-/- and Cd22Y2,5,6F primary B cells were treated with vehicle control (-) or 1 µM LatA for the indicated time. Cells were lysed and analysed by SDS-PAGE followed by immunoblotting with phospho-CD19 (pCD19), phospho-Akt (pAkt), phospho-ERK (pERK) and actin as loading control. The intensity of phosphorylated proteins, normalized to actin, was referred to the unstimulated sample of the wild type cells, set as 1.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(A-B) Wild-type and CD45-deficient primary B cells were stained with Alexa647conjugated antibody against CD22 and settled onto nonstimulatory coverslips. Cells were then fixed, imaged with dSTORM and analysed.(A) 2D (top) and pseudo 3D (bottom) dSTORM images were reconstructed from single molecule localizations. The white dashed square is shown in pseudo 3D (bottom).(B) Error bars (Hopkins index) and thin lines (H function) denote mean ± SEM. Data are pooled from three experiments.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(C-E) Wild-type and CD45-deficient primary B cells were labelled with Atto633-conjugated Fab fragments against CD22 or IgM, settled onto nonstimulatory coverslips and imaged. Single particle trajectories were then analysed.(C) Trajectories of CD22 in wild-type (left) and CD45-deficient cells (right) showing diffusion of single particles over 6 s.(D) Diffusion coefficients of 300 representative CD22 and IgM particles. Bars and numbers indicate the median. Data are pooled from three experiments.(E) Confinement analysis of CD22 and IgM. Bars and numbers indicate the median.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(F) Two-population analysis of CD22 diffusion. Diffusion coefficient were plotted on a logarithmic scale and fitted to two Gaussian-shaped curves to account for slower (light grey) and faster (dark grey) diffusing populations. Wild-type (blue line and circles, left) and CD45-deficient (blue line and squares, left middle) primary B cells were compared in an overlay (right middle) and their proportions plotted (right).",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(G and H) CD45-deficient primary B cells were labelled with Atto633-conjugated Fab fragments against CD22 or IgM, settled onto nonstimulatory coverslips, treated with vehicle control (DMSO) or 1µM LatA and imaged. Single particle trajectories were then analysed and diffusion coefficients calculated.(G) Diffusion coefficients of 300 representative CD22 and IgM particles. Bars and numbers indicate the median.(H) Confinement analysis. Bars and numbers indicate the median.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(I and J) CD45-deficient primary B cells were stained with Alexa 647-conjugated antibody against CD22, settled onto nonstimulatory coverslips and treated with vehicle control or sialidase. Cells were then fixed, imaged with dSTORM and analysed.(I) 2D (top) and pseudo 3D (bottom) dSTORM images were reconstructed from single molecule localizations. The white dashed square is shown in pseudo 3D (bottom).(J) Quantification of the distribution of CD22 with Hopkins index and H function. Error bars (Hopkins index) and thin lines (H function) denote mean ± SEM.Data are pooled from two experiments.*P<0.05, **P<0.001, ***P<0.0001 (Student's t-test).",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(K and L) Wild-type and CD45-deficient primary B cells were treated with vehicle control (-) or 1 µM LatA for the indicated times. Cells were lysed and analysed by SDS-PAGE followed by immunoblotting with phospho-CD22 (p-CD22) and total CD22 as loading control. The intensity of p-CD22, normalized to CD22, was referred to the unstimulated sample of the wild-type cells, set as 1.",
    "ncbi_link": "CD45: 19264"
  },
  {
    "caption": "(A-E) Wild-type and Cd22R130E primary B cells were labelled with Atto 633-conjugated Fab fragments against CD22 or IgM, settled onto nonstimulatory coverslips and imaged. Single particle trajectories were then analysed.(A) Trajectories of CD22 in Wild-type (left) and Cd22R130E cells (right) showing diffusion of single particles over 6 s.B) Diffusion coefficients of 300 representative CD22 and IgM particles. Bars and numbers indicate the median.(C) Confinement analysis. Bars and numbers indicate the median.(D and E) Two-population analysis of CD22 diffusion. Analysis of CD22 diffusion plotted on a logarithmic scale and fitted to two Gaussian-shaped curves to account for slower and faster diffusing populations.(D) Wild-type (blue line and circles) and Cd22R130E (blue dotted line and squares middle) primary B cells were compared in an overlay (left) and the proportions of the faster diffusing populations plotted (right).(E) Proportions of faster-diffusing populations.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(F and G) Wild-type and Cd22R130E primary B cells were stained with Alexa 647-conjugated antibody against CD22 and settled onto nonstimulatory coverslips. Cells were then fixed, imaged with dSTORM and analysed.(F) 2D (top) and pseudo 3D (bottom) dSTORM images were reconstructed from single molecule localizations. The white dashed square is shown in pseudo 3D (bottom).(G) Quantification of the distribution of CD22 with Hopkins index and H function. Error bars (Hopkins index) and thin lines (H function) denote mean ± SEM. Data are pooled from three experiments.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(H) Wild-type and Cd22R130E primary B cells were treated with 1 µM LatA and intracellular calcium flux was measured by flow cytometry.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "(I-K) Wild-type and Cd22R130E primary B cells were treated with vehicle control (-) or 1 µM LatA for the indicated time. Cells were lysed and analysed by SDS-PAGE followed by immunoblotting with phospho-CD19 (p-CD19), phospho-Akt (pAkt), phospho-ERK (pERK) and actin and total ERK as loading controls. The intensity of phosphorylated proteins, normalized to actin or ERK, was referred to the unstimulated sample of the wild type cells, set as 1.Data are representative of at least two experiments.",
    "ncbi_link": "Cd22: 12483"
  },
  {
    "caption": "Slices through electron cryo-tomograms showing fully-assembled motors without the hook and filament. The dashed-yellow circles indicate the IM sub-complex. Schematic representation of the P. aeruginosa motors lacking the hook and filament shown in (A-C). Slices through electron cryo-tomograms showing fully-assembled motors with the hook and lacking the filament. Schematic representation of the motors with the hook shown in (E-G). Slices through electron cryo-tomograms of intact P. aeruginosa ∆flgI cells showing the presence of the inner-membrane sub-complex with the rod. Schematic representation of the inner-membrane sub-complex with the rod shown in (I-K). Slices through electron cryo-tomogram of lysed P. aeruginosa ∆flgI cells showing the presence of the sub-complex constituting the MS-ring and the rod. Schematic representation of the sub-complex described in (M-O). A slice through an electron cryo-tomogram of a P. aeruginosa ∆flgG cell highlighting the presence of the inner-membrane sub-complex. Schematic representation of the inner-membrane sub-complex shown in (Q).",
    "ncbi_link": "flgG: 880935
flgI: 878536"
  },
  {
    "caption": "Slices through electron cryo-tomograms of wild type cells showing fully-assembled motors without the hook and filament. Schematic representation of the motors lacking the hook and filament shown in (A-C). Sub-tomogram average of the motors of fully-assembled flagella. Slice through an electron cryo-tomogram of a ΔflgH cell showing an IM sub-complex, indicated by the dashed-yellow circle. Schematic representation of the IM sub-complex shown in (F). Slices through electron cryo-tomograms of ΔflgH cells showing the IM sub-complex with the rod and the P-ring, indicated by the dashed-yellow circles. Schematic representation of the structures shown in (H and I). Slices through electron cryo-tomograms of ΔflaA/B cells highlighting the flagellar motor and the hook (without the filament). Sub-tomogram average of the flagellar motor and the hook structure found in ΔflaA/B cells. Schematic representation of the sub-tomogram average shown in (N). Slices through electron cryo-tomograms of ΔflaA/B cells illustrating a disassembly product constituting the PL sub-complex, the rod and the hook. Sub-tomogram average of the disassembly complex shown in (P-R). The dashed-orange arrow indicates the absence of the IM sub-complex in this structure. Schematic representation of the disassembly product shown in (P-S). Slices through electron cryo-tomograms of ΔflaA/B cells highlighting PL sub-complexes (dashed-yellow circles). Sub-tomogram average of the PL sub-complexes in ΔflaA/B cells. Schematic representation of the sub-tomogram average shown in (X).",
    "ncbi_link": "flaA: 1170946
flgH: 1170937"
  },
  {
    "caption": "K) Western blot of Ub-K48 proteins in the insoluble fraction of protein lysates of SOD1-G93A mouse spinal cord plus or minus heat shock. L) Quantification of panel K. Each central line and error bar indicate mean +/- SEM of a biological replicates (n=5 biological replicates per group) Data information: * indicates p<0.05, ** indicates p<0.005, and *** indicates p<0.0005 by unpaired two tailed students t-test comparing male and female samples or samples with or without heat shock.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "M) Chymotrypsin-like proteasome activity in spinal cord lysates from SOD1-G93A mice. Each central line and error bar indicate mean +/- SEM of a biological replicates (n=5 biological replicates per group). Bordered points indicate biological replicates and un-bordered points indicate technical replicates. Data information: * indicates p<0.05, ** indicates p<0.005, and *** indicates p<0.0005 by unpaired two tailed students t-test comparing male and female samples or samples with or without heat shock.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "N) Filter trap assay of protein lysates from the insoluble fraction of SOD1-G93A spinal cord lysates plus or minus heat shock. O) Quantification of panel N. Each central line and error bar indicate mean +/- SEM of a biological replicates (n=5 biological replicates per group) Data information: * indicates p<0.05, ** indicates p<0.005, and *** indicates p<0.0005 by unpaired two tailed students t-test comparing male and female samples or samples with or without heat shock.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "P) Representative transmission electron micrographs of protein aggregates in the insoluble fraction of SOD1-G93A spinal cord lysates plus or minus heat shock. Scale bar equals 600nm. Q) Quantification of P. (n=9 technical replicates per group) Data information: * indicates p<0.05, ** indicates p<0.005, and *** indicates p<0.0005 by unpaired two tailed students t-test comparing male and female samples or samples with or without heat shock.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "FLMycER cells, primed or not with OHT  (48h), were treated with 135 nm  IACS-010759 (IACS) for 48 hours (B) H2O2  quantification, expressed as fold-increase of the 405/488 nm fluorescence ratio in treated vs. untreated  FLMycER cells, expressing either the cytoplasmic  (left) or mitochondrial  (right) roGFP2-ORP1  biosensor. Data information: * p ≤ 0.05 (one-way ANOVA). Each point in the graphs in B from an independent biological replicate, each representing the average of thousands of events (single cells) in a distinct cell population, normalized to the untreated condition.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "FLMycER cells, primed or not with OHT  (48h), were treated with 135 nm IACS-010759 (IACS) for 48 hours (C) Superoxide anion O2•-  production in treated vs. untreated FLMycER cells, based on dihydroethidium staining. Data information: * p ≤ 0.05 (one-way ANOVA). Each point in the graphs in B and C is from an independent biological replicate, each representing the average of thousands of events (single cells) in a distinct cell population, normalized to the untreated condition.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "FLMycER cells were primed with100 nM OHT  (48h) and/or treated with 135nM IACS-010759, as indicated. (B) glutathione  quantification in FLMycER cells, measured after 40 hours of IACS-010759 treatment. Data information: n=3 biological replicates; error bars: SD. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001 (one-way ANOVA).",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "(F) Immunoblot  on lysates from FLMycER cells treated as indicated, with the addition of 10 mM NAC  concomitantly with IACS-010759.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "FLMycER  cells were primed with 100 nM OHT  and treated with 135 nM  IACS-010759, as indicated. (B) NADPH/NADP redox state in  FLMycER cells, assayed after 40 hours of IACS-010759 treatment. n=3 biological replicates. ** p ≤ 0.01; **** p ≤ 0.0001 (one-way ANOVA).",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "FLMycER cells were primed with 100 nM OHT  and treated with 135 nM  IACS-010759, as indicated. (E-G) Cell viability after 40 hours of IACS-010759 treatment in the presence of (E) 50 µM dehydroepiandrosterone  (DHEA), (F) 10 µM 6- aminonicotinamide  (6AN) or (G) 1 mM  2-deoxyglucose (2DG). See Supplemental Figure3F for detailed statistical analysis. Data information: In E,G) n=6; in (F) n=9; all biological replicates; error bars: SD.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "(A) Viability  of FLMycER and BaFMycER cells primed or not with 100 nM OHT  and treated with 135 nM IACS-010759 for 48h and/or with ascorbate  at the indicated concentration for 6h. n=3 biological replicates; error bars: SD.",
    "ncbi_link": "Myc: 17869"
  },
  {
    "caption": "F Comparison of TAZ gene expression, normalized to S12, in heart, liver, and kidney, analyzed in triplicates by quantitative PCR. n= 5 per genotype.G TAZ gene expression in percent. Wild-type is set to 100%.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "D Respiratory chain complexes in cardiac mitochondria were separated on BN-PAGE and stained for activity of complex I, II, IV and F1FO- ATPase. sh, shTAZ; Q, ubiquinone.",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "C Steady state protein levels analyzed by SDS gel separation of indicated amounts of mitochondrial protein and subsequent Western- blotting with antibodies against SDHA and VDAC3 or visualizing of Flavin fluorescence after excitation with 488 nm. Lower panel: quantification of signal ratio SDHA/VDAC3 in shTAZ and control (set to 100%).",
    "ncbi_link": "TAZ: 66826"
  },
  {
    "caption": "D Analysis of gene expression in cardiac tissue analyzed in (C) by qPCR using primers against indicated mRNA. Data of one representative measurement, normalized to b-actin with WT set to 100% are shown. Identical results were obtained in further experiments with two different pairs of animals.",
    "ncbi_link": "b-actin: "
  },
  {
    "caption": "B RT-PCR showing the expression of indicated genes in undifferentiated iPSCs and differentiated iPSC-CMs of BTHS patient TAZ10 and a healthy control.",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "D Quantitation of sarcomere organization. Left panel: Immunostaining of cTNT, MLC2a (myosin light chain) and a-actinin at day 60 post cardiac differentiation. Right panel: The bar graphs at the right panel represent the sarcomere regularity from 3 independent experiments. Error bars represent standard deviation for the comparison between control and BTHS patient TAZ10. Significance was analyzed using Student's T-TEST **P = 0.002 and ***P = 0.0006. Scale bars: 50 µm.",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "A Oxygen consumption rate (OCR) of cardiomyocytes from patient TAZ10 and control at basal conditions and after the administration of the indicated compounds.",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "D Analysis of SDHA gene expression in triplicates by qPCR in cardiomyocytes, analyzed in (C).",
    "ncbi_link": "SDHA: 6389"
  },
  {
    "caption": "A Expression  of PTPN11 (gene encoding SHP2) in skin lesions in psoriatic patients  compared with skin  from healthy donors based on microarray data (No. GSE14905). B Expression of ptpn11  in human PBMCs  of psoriatic patients (n=14) and normal controls (n=16). Data information: Data are represented mean ± SEM. P values are determined by two-tailed Mann-Whitney U test *P<0.05, **P<0.01.",
    "ncbi_link": "ptpn11: 5781
PTPN11: 5781
SHP2: 5781"
  },
  {
    "caption": "G  Quantitative PCR  analysis of Ptpn11 mRNA levels in the  IMQ-treated or non-treated  dorsal  back of C57BL/6  mice  at day 5 (n=6/group). Data were normalized to Gapdh expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "ncbi_link": "Gapdh: 14433
Ptpn11: 19247"
  },
  {
    "caption": "Quantitative PCR analysis of mRNA encoding  IL-23/IL-17A axis cytokines in the dorsal skin of C57BL/6 mice treated with indicated dose of SHP099  or vehicle for 4 days. Results were normalized to  Gapdh expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "ncbi_link": "Gapdh: 14433
IL-17A: 16171
IL-23: 83430"
  },
  {
    "caption": "ELISA  quantification of protein levels of cytokines in mouse serum. Quantitative PCR analysis of mRNA encoding  psoriasis-related cytokines in the dorsal skin of C57BL/6 mice treated with indicated dose of SHP099  or vehicle for 4 days. Results were normalized to Gapdh  expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test *P<0.05, **P<0.01.",
    "ncbi_link": "Gapdh: 14433"
  },
  {
    "caption": "Representative images (A and E), histological  sections of dorsal back (B and F) and clinical scores (C and G) and quantitative PCR  analysis of mRNA levels in dorsal skin  (D and H) from wild-type (n=6) and M-Shp2-/- mice  or DC-Shp2-/- mice (n=6) treated with IMQ for 4 days. Scale bar: 100 μm. Left: H&E  (hematoxylin and eosin) staining data; right: statistical data (mean ± SEM). Results were normalized to Gapdh expression. Data information: Data are represented mean ± SEM. P values were calculated by Tukey multiple comparison test (B, D, F, H) or Bonferroni multiple comparison test (C, G). *P<0.05, **P<0.01, ns, not significant.",
    "ncbi_link": "Gapdh: 14433
Shp2: 19247"
  },
  {
    "caption": "A Heat map showing mRNA expression  in peritoneal macrophages derived from wild-type and M-Shp2-/- mice after IMQ treatment based on RNA sequencing (n=3/group). Colors represent high (red) and low (blue) intensity. Genes labeled in green indicate they are in the NF-κB signaling.",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": "D BMDMs and PMs derived from wild-type and M-Shp2-/- mice were stimulated by IMQ  (10 µg/ml) for indicated times. Whole cell lysates were subjected to Western blotting.",
    "ncbi_link": "Shp2: 19247"
  },
  {
    "caption": "E  Immunoblotting  of HEK293T cells co-transfected for 48 h with GFP-TLR7, plus HA-SHP2, HA-SHP2 mutant vectors, followed by immunoprecipitation with anti-GFP beads.",
    "ncbi_link": "GFP: 
HA: 
SHP2: 5781
TLR7: 51284"
  },
  {
    "caption": "F PMA-differentiated THP-1 cells were infected with vector or SHP2 lentivirus  and then treated with or without R848  (10 µg/ml). Subcellular fractionation was performed, and cytoplasmic and cell membrane proteins were probed by respective antibodies.",
    "ncbi_link": "SHP2: 5781"
  },
  {
    "caption": "G, H  Immunoblot  analysis of TLR7  and SHP2 in the isolated ER, Golgi and endosome from PMA-differentiated THP-1  cells with either SHP2 overexpressed (G) and SHP2  deficiency(H).",
    "ncbi_link": "SHP2: 5781"
  },
  {
    "caption": "B,  Immunoblotting of TLR7  in the endosome isolated from HEK293T cells that were transfected with GFP-TLR7  or GFP-TLR7 mutant vectors.",
    "ncbi_link": "GFP: 
TLR7: 51284"
  },
  {
    "caption": "G HEK293T  cells transfected with NF-κB-luciferase  reporter and indicated TLR7  mutant vectors and then treated with  IMQ (10 µg/ml) for 24 h were harvested for luciferase assay. Data information: Data are represented mean ± SEM. P values are determined by two-tailed unpaired Student's t-test **P<0.01, ns, not significant.",
    "ncbi_link": "luciferase: 
NF-κB: 4794///84807///4793///64332///4792
TLR7: 51284"
  },
  {
    "caption": "Tlr7wt/wt female mice (n=6) and Tlr7-Y1025D mutant Tlr7ki/wt female  mice (n=6) and  Tlr7ki/ki female  mice (n=5) were treated with indicated dose of IMQ for 4 days. A Phenotypic presentation (top) and H&E staining (bottom) of dorsal skin. Scale bar: 100 μm. Left: H&E staining data; right: statistical data (mean ± SEM). Data information: Data are represented mean ± SEM. P values are determined by two-tailed Mann-Whitney U test *P<0.05, **P<0.01.",
    "ncbi_link": "Tlr7: 170743"
  },
  {
    "caption": "Tlr7wt/wt female mice  (n=6) and Tlr7-Y1025D mutant Tlr7ki/wt female mice (n=6) and Tlr7ki/ki female mice (n=5) were treated with indicated dose of IMQ  for 4 days. D Quantitative PCR analysis of mRNA encoding IL-23/IL-17A axis cytokines and other psoriasis-related cytokines in the dorsal skin. Results were normalized to  Gapdh expression. Data information: Data are represented mean ± SEM. P values are determined by two-tailed Mann-Whitney U test *P<0.05, **P<0.01.",
    "ncbi_link": "Gapdh: 14433
Tlr7: 170743"
  },
  {
    "caption": "Tlr7wt/wt female  mice (n=6) and Tlr7-Y1025D mutant Tlr7ki/wt female  mice (n=6) and Tlr7ki/ki female mice (n=5) were treated with indicated dose of IMQ  for 4 days. E Representative p-p65 staining of the dorsal skin. Scale bars: 100 μm.",
    "ncbi_link": "Tlr7: 170743"
  },
  {
    "caption": "(G) Tumour growth (in mm3) of FBXW7+/+ and FBXW7-/- xenografts in nude mice (n=10 animals per group). Treatment with either vehicle, paclitaxel (1,5mg/kg) or tigecycline (50mg/kg) started at day 6 post-tumour-injection, and was administered three times per week. Error bars indicate SEM. (H) Representative images of the xenografts defined in (G) at day 15.",
    "ncbi_link": "FBXW7: 55294"
  },
  {
    "caption": "A, The indicated cells co-transfected with p5HRE-Luc and either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (empty vector: EV) were cultured under the indicated oxygen conditions for 24 hours for the luciferase assay. B, U2OS cells co-transfected with p5HRE-Luc and the indicated siRNA were cultured under the indicated oxygen conditions for 24 hours for the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
ZBTB2: 57621"
  },
  {
    "caption": "C, HCT116 p53-/- cells co-transfected with p5HRE-Luc, either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV), and either pcDNA3/p53 (at two concentrations: + and ++) or pcDNA3 (EV) were cultured under the indicated oxygen conditions for 24 hours for the luciferase assay and Western blotting using the indicated antibodies.",
    "ncbi_link": "His B: 
Luc: 
myc: 
p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "D, HCT116 p53+/+ cells co-transfected with p5HRE-Luc, either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV), and either pcDNA3/p53 R175H, R248W, R273H, or pcDNA3 (EV) were cultured under the indicated oxygen conditions for 24 hours for the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV) either pcDNA3/p53 (p53) or pcDNA3 (EV) (C) with the indicated siRNA were cultured under < 0.1% O2 conditions for 24 hours and subjected to qRT-PCR for the indicated mRNA",
    "ncbi_link": "His B: 
myc: 
p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV) to the transwell invasion assay",
    "ncbi_link": "His B: 
myc: 
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with either pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV) with the indicated siRNA or to the transwell invasion assay",
    "ncbi_link": "His B: 
myc: 
ZBTB2: 57621"
  },
  {
    "caption": "G, The number of metastatic colonies in lungs in the pulmonary metastasis model using the indicated cells stably transfected with ZBTB2 expression vector (ZBTB2) or its empty vector (EV) (left) and the representative images of lungs (right).",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells stably transfected with the ZBTB2 expression vector (ZBTB2) or its empty vector (EV) (H) were cultured under < 0.1% O2 (H) for the indicated periods and subjected to the in vitro cell proliferation assay.",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells stably transfected with the ZBTB2 expression vector (ZBTB2) transiently transfected with siScr or siZBTB2 (I) the indicated oxygen conditions (I) for the indicated periods and subjected to the in vitro cell proliferation assay.",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "J,K, Growth of the indicated tumor xenografts with or without ZBTB2 overexpression was analyzed.",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "C, Kaplan-Meier analysis of the disease-free survival of the lung cancer patients stratified by the expression levels of ZBTB2 and p53 status.",
    "ncbi_link": "p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "D-F, TCGA-based Kaplan-Meier analysis of overall survival of lung adenocarcinoma patients stratified by the expression levels of ZBTB2 and those of BAX (D), ZMAT3 (E), and CEACAM1 (F).",
    "ncbi_link": "BAX: 581
CEACAM1: 634
ZBTB2: 57621
ZMAT3: 64393"
  },
  {
    "caption": "A, The indicated cells transiently transfected with pEF6/ZBTB2 (ZBTB2) or pEF6/myc-His B (EV) were cultured under the indicated oxygen conditions for 24 hours and subjected to Western blotting using the indicated antibodies.",
    "ncbi_link": "His B: 
myc: 
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with both pG5H1bLuc and either pcDNA6/Gal4 DBD-HIF-1α TAD P564A pcDNA6/Gal4 DBD-HIF-1α TAD P564A and N803A (E) were additionally co-transfected with either pEF6/myc-His B (EV), pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 del[1-23] (del[1-23]), pEF6/ZBTB2 del[BTB/POZ] (del[BTB]), pEF6/ZBTB2 del[ZF1] (del[ZF1]), pEF6/ZBTB2 del[ZF2] (del[ZF2]), pEF6/ZBTB2 del[ZF3] (del[ZF3]), or pEF6/ZBTB2 del[ZF4]- (del[ZF4]), as indicated with the indicated siRNA The cells were then cultured under the indicated oxygen conditions for 24 hours and subjected to the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
Gal4: 855828
HIF-1α: 3091
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with both pG5H1bLuc and either pcDNA6/Gal4 DBD-HIF-1α TAD P564A were additionally co-transfected with either pEF6/myc-His B (EV), pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 del[1-23] (del[1-23]), pEF6/ZBTB2 del[BTB/POZ] (del[BTB]), pEF6/ZBTB2 del[ZF1] (del[ZF1]), pEF6/ZBTB2 del[ZF2] (del[ZF2]), pEF6/ZBTB2 del[ZF3] (del[ZF3]), or pEF6/ZBTB2 del[ZF4]- (del[ZF4]), as indicated with the indicated siRNA The cells were then cultured under the indicated oxygen conditions for 24 hours and subjected to the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
Gal4: 855828
HIF-1α: 3091
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with pcDNA6/Gal4 DBD-HIF-1α TAD P564A and N803A (E) were additionally co-transfected with either pEF6/myc-His B (EV), pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 del[1-23] (del[1-23]), pEF6/ZBTB2 del[BTB/POZ] (del[BTB]), pEF6/ZBTB2 del[ZF1] (del[ZF1]), pEF6/ZBTB2 del[ZF2] (del[ZF2]), pEF6/ZBTB2 del[ZF3] (del[ZF3]), or pEF6/ZBTB2 del[ZF4]- (del[ZF4]), as indicated (B,D,E,F) The cells were then cultured under the indicated oxygen conditions for 24 hours and subjected to the luciferase assay.",
    "ncbi_link": "His B: 
myc: 
Gal4: 855828
HIF-1α: 3091
ZBTB2: 57621"
  },
  {
    "caption": "The indicated cells transiently transfected with both pG5H1bLuc and either pcDNA6/Gal4 DBD-HIF-1α TAD P564A were additionally co-transfected with either pEF6/myc-His B (EV), pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 del[1-23] (del[1-23]), pEF6/ZBTB2 del[BTB/POZ] (del[BTB]), pEF6/ZBTB2 del[ZF1] (del[ZF1]), pEF6/ZBTB2 del[ZF2] (del[ZF2]), pEF6/ZBTB2 del[ZF3] (del[ZF3]), or pEF6/ZBTB2 del[ZF4]- (del[ZF4]), as indicated The cells were then cultured under the indicated oxygen conditions for 24 hours and subjected to the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
Gal4: 855828
HIF-1α: 3091
ZBTB2: 57621"
  },
  {
    "caption": "H, After transient transfection with the expression vectors for ZBTB2-V5, ZBTB2-myc, or their empty vector (-), ZBTB2-myc protein was immunoprecipitated using the anti-myc antibody and co-precipitated ZBTB2-V5 was detected using the anti-V5 antibody (upper). One-tenth of the whole cell lysate (WCL) was subjected to immunoblotting with the indicated antibodies (lower).",
    "ncbi_link": "myc: 
V5: 
ZBTB2: 57621"
  },
  {
    "caption": "I,J, The indicated cells transiently transfected with or without either pcDNA4/ZBTB2-LgBiT or pcDNA4/LgBiT and either pcDNA4/ZBTB2-SmBiT or pcDNA4/SmBiT, as indicated, were cultured under < 0.1% oxygen (I) or the indicated oxygen conditions (J) and subjected to the split luciferase complementation assay.",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "K, HeLa cells overexpressing wildtype or the indicated mutant of ZBTB2 (ZF2 or ZF3-deletion) were cultured under < 0.1% oxygen conditions, and subjected to immunoprecipitation with anti-myc antibody. Coprecipitated DNA was subjected to the qRT-PCR experiment using primers against HRE regions of the STC1 promoter.",
    "ncbi_link": "STC1: 6781
ZBTB2: 57621"
  },
  {
    "caption": "L, The same experiment as I was conducted using the indicated combination of pcDNA4/ZBTB2-LgBiT (WT), pcDNA4/ZBTB2ΔZF2-LgBiT (ΔZF2), or pcDNA4/ZBTB2ΔZF3-LgBiT (ΔZF3), and pcDNA4/ZBTB2-SmBiT (WT), pcDNA4/ZBTB2ΔZF2-SmBiT (ΔZF2), or pcDNA4/ZBTB2ΔZF3-SmBiT (ΔZF3).",
    "ncbi_link": "ZBTB2: 57621"
  },
  {
    "caption": "B, HCT116 p53-/- cells co-transfected with pG5H1bLuc, pcDNA6/Gal4 DBD-HIF-1α TAD P564A, and either pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 del[8-11] (ZBTB2 del[8-11]), pEF6/ZBTB2 del[51-54] (ZBTB2 del[51-54]), or pEF6/myc-His B (EV), as indicated, were cultured under < 0.1% oxygen conditions for 24 hours and subjected to the luciferase assay.",
    "ncbi_link": "His B: 
Luc: 
myc: 
Gal4: 855828
HIF-1α: 3091
p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "C, After transient transfection with or without the expression vectors for ZBTB2-V5, ZBTB2 4A-V5, ZBTB2-myc, ZBTB2 4A-myc, or their empty vector, as indicated, the myc-fused proteins were immunoprecipitated using an anti-myc antibody and co-precipitated ZBTB2-V5 or ZBTB2 4A-V5 was detected (upper). One-tenth of the whole cell lysate (WCL) was subjected to immunoblotting with the indicated antibodies (lower).",
    "ncbi_link": "myc: 
V5: 
ZBTB2: 57621"
  },
  {
    "caption": "D, HCT116 p53-/- (left) cells transiently transfected with or without either pcDNA4/ZBTB2-LgBiT (ZBTB2), pcDNA4/ZBTB2 4A-LgBiT 4A (4A), or pcDNA4/LgBiT (-) and either pcDNA4/ZBTB2-SmBiT (ZBTB2), pcDNA4/ZBTB2 4A-SmBiT (4A), or pcDNA4/SmBiT (-), as indicated, were cultured under < 0.1% oxygen and subjected to the split luciferase complementation assay.",
    "ncbi_link": "p53: 7157
ZBTB2: 57621"
  },
  {
    "caption": "G, The same kind of luciferase assay to quantify the transactivation activity as B was carried out using either pEF6/ZBTB2 (ZBTB2), pEF6/ZBTB2 4A (4A), or pEF6/myc-His B (EV).",
    "ncbi_link": "His B: 
myc: 
ZBTB2: 57621"
  },
  {
    "caption": "C. Capillary sequencing for Rnaseh2b+/+, Rnaseh2bA174T/+, and Rnaseh2bA174T/A174T DNA confirmed the presence of the introduced missense mutation.",
    "ncbi_link": "Rnaseh2b: 67153"
  },
  {
    "caption": "D. Mouse genotyping by multiplex PCR. Top: A 221 bp PCR product is present in wild-type mice (+/+); the Rnaseh2bA174T allele (also) give a 460 bp product. Bottom: Position of forward (x) and reverse primers (y, z).",
    "ncbi_link": "Rnaseh2b: 67153"
  },
  {
    "caption": "E. Immunoblotting demonstrates depletion of all three RNase H2 protein subunits in Rnaseh2bA174T/A174T MEFs and RNASEH2BA177T/A177T LCLs. Representative of three independent experiments.",
    "ncbi_link": "RNASEH2B: 79621
Rnaseh2b: 67153"
  },
  {
    "caption": "G, H. RNase H2 enzyme activity is reduced in mouse and patient cells. (G) Enzyme activity for Rnaseh2bA174T/A174T MEFs and passage-matched Rnaseh2b+/+ controls, against RNase H substrate (RNA:DNA heteroduplex) and RNase H2-specific substrate, double stranded DNA with a single embedded ribonucleotide (DRD:DNA). Mean activity for three independent cell lines, error bars, SEM. Enzymatic activity expressed relative to the average value of control MEFs. *** = p<0.001, two-tailed t-test (n=3 Rnaseh2bA174T/A174T and n=3 Rnaseh2b+/+ control MEF lines). (H) RNase H2 activity in LCLs from two independent healthy controls and an AGS patient homozygous for the RNASEH2B-A177T mutation. Enzyme activity normalised to average activity of control lines. Three independent experiments, error bars SEM. *** = p<0.001 versus either control, two-tailed t-test.",
    "ncbi_link": "Rnaseh2b: 67153
RNASEH2B: 79621"
  },
  {
    "caption": "Figure 2. Increased ISG expression in tissues from Rnaseh2bA174T/A174T miceA. Transcript levels of multiple ISGs are significantly elevated in heart.B. Transcript levels of a subset of ISGs are significantly increased in kidney.C. No ISG upregulation is evident in the brain. ISG transcript levels determined by RT-qPCR normalised to transcript levels of the housekeeping gene HPRT (Oas1a was undetectable in brain). Each data point represents the mean of technical replicates of tissue RNA from a single mouse. n=9 nine-month old Rnaseh2bA174T/A174T mice, n=4 age-matched control wildtype C57BL/6Jmice. Horizontal line, mean; error bars, SEM. * = p<0.05, ** = p<0.01, two-tailed t-test.",
    "ncbi_link": "HPRT: 15452
Oas1a: 246730
Rnaseh2b: 67153"
  },
  {
    "caption": "A. Validation of Rnaseh2b-/- MEF lines. RER activity (DRD:DNA) is undetectable in a Rnaseh2b-/- line consistent with complete inactivation of the Rnaseh2b gene (Reijns et al, 2012). Mean of three independent experiments; error bars, SEM, **** = p<0.0001, two-tailed t-test. Rnaseh2b-/- and Rnaseh2b+/+ control MEFs on a C57BL/6 p53-/- background.",
    "ncbi_link": "Rnaseh2b: 67153
p53: 22059"
  },
  {
    "caption": "B. ISG transcript levels are increased in Rnaseh2b-/- MEFs.",
    "ncbi_link": "Rnaseh2b: 67153"
  },
  {
    "caption": "C. BeadArray transcript analysis (Illumina) detected induction of multiple ISGs, including the cytokines CXCL10 and CCL5, but not other cytokine transcripts in Rnaseh2b-/- MEFs. Plotted, average fold enrichment versus p-value of significantly upregulated transcripts (p<0.05, after multiple testing correction) comparing two Rnaseh2b-/- MEF lines versus 4 Rnaseh2b+/+ MEF lines. 17 out of 29 transcripts are ISGs.",
    "ncbi_link": "CCL5: 20304
CXCL10: 15945
Rnaseh2b: 67153"
  },
  {
    "caption": "D. CXCL10 and CCL5 transcripts (detected by RT-qPCR) are significantly elevated.",
    "ncbi_link": "CCL5: 20304
CXCL10: 15945"
  },
  {
    "caption": "E. Increased CXCL10 and CCL5 protein (detected by ELISA) is secreted by Rnaseh2b-/- MEFs. (B, D, E) Mean data from three experiments for six independent Rnaseh2b-/- MEF lines versus four independent Rnaseh2b+/+ MEF lines. Error bars, SEM. * = p<0.05, ** = p<0.01, Mann-Whitney U test.",
    "ncbi_link": "Rnaseh2b: 67153"
  },
  {
    "caption": "A. ISG activation and cytokine secretion in Rnaseh2b-/- MEFs is markedly impaired by cGAS or STING siRNA depletion. Upper left and lower panels: RT-qPCR of IFIT1, cGAS and STING transcripts, 48 h after siRNA targeting luciferase (control), cGAS or STING. Upper right panel: CCL5 is significantly reduced in culture supernatants 48 h after cGAS or STING depletion. Concentration of CCL5 (ELISA), normalised to luciferase siRNA control levels in each experiment. Mean from three independent experiments using one Rnaseh2b-/- MEF line; error bars, SEM. * = p<0.05, ** = p<0.01, two-tailed t-test for RT-qPCR, one sample t-test for CCL5ELISA.",
    "ncbi_link": "luciferase: 
IFIT1: 15957
cGAS: 214763
Rnaseh2b: 67153
STING: 72512"
  },
  {
    "caption": "B-D. ISG induction and cytokine secretion is abolished in Rnaseh2b-/- cGAS-/- MEFs. cGAS was targeted by CRISPR/Cas9 genome editing of a Rnaseh2b-/- MEF line to inactivate cGAS/STING signalling. In addition to sequence validation, functional inactivation of cGAS was confirmed in Rnaseh2b-/- cGas-/- CRISPR lines by the absence of CCL5 secretion in response to dsDNA (Appendix Fig S4). CCL5 (B) and CXCL10 (C) production, as well as ISG expression (D) was abrogated in Rnaseh2b-/- cGAS-/- clones, assessed by ELISA and RT-qPCR respectively. Four independent experiments, n=2 Rnaseh2b-/- cGAS-/- clones, n=4 Rnaseh2b-/- cGAS+/+ clones, error bars, SEM of each experiment * = p<0.05, ** = p<0.01, *** = p<0.001, two-tailed t-test.",
    "ncbi_link": "Cas9: 
CRISPR: 
cGAS: 214763
cGas: 214763
Rnaseh2b: 67153"
  },
  {
    "caption": "B-D. ISG induction and cytokine secretion is abolished in Rnaseh2b-/- cGAS-/- MEFs. cGAS was targeted by CRISPR/Cas9 genome editing of a Rnaseh2b-/- MEF line to inactivate cGAS/STING signalling. In addition to sequence validation, functional inactivation of cGAS was confirmed in Rnaseh2b-/- cGas-/- CRISPR lines by the absence of CCL5 secretion in response to dsDNA (Appendix Fig S4). CCL5 (B) and CXCL10 (C) production, as well as ISG expression (D) was abrogated in Rnaseh2b-/- cGAS-/- clones, assessed by ELISA and RT-qPCR respectively. Four independent experiments, n=2 Rnaseh2b-/- cGAS-/- clones, n=4 Rnaseh2b-/- cGAS+/+ clones, error bars, SEM of each experiment * = p<0.05, ** = p<0.01, *** = p<0.001, two-tailed t-test.",
    "ncbi_link": "Cas9: 
CRISPR: 
CCL5: 20304
CXCL10: 15945
cGAS: 214763
cGas: 214763
Rnaseh2b: 67153
STING: 72512"
  },
  {
    "caption": "E. ISG induction in Rnaseh2bA174T/A174T mice is STING dependent. RT-qPCR of RNA extracted from hearts from Sting+/+ Rnaseh2bA174T/A174T (n=4) and Sting-/-Rnaseh2bA174T/A174T (n=6) three-month old mice.",
    "ncbi_link": "Rnaseh2b: 67153
Sting: 72512
STING: 72512"
  },
  {
    "caption": "F. Absence of STING does not significantly decrease basal ISG expression. RT-qPCR of RNA extracted from hearts from Sting+/+ (n=3) and Sting-/- (n=5) three-month old mice. (E, F) Each data point represents the mean of technical triplicates from one mouse. Error bars, SEM. * = p<0.05, Mann-Whitney U test.",
    "ncbi_link": "STING: 72512
Sting: 72512"
  },
  {
    "caption": "A. Overexpression of RNase H1 in Rnaseh2b-/- cells restores RNase H activity against RNA:DNA hybrids to 81 ± 10% of wildtype levels, while overexpression of RNase H2B restores cellular enzyme activity for cleavage of both RNA:DNA and DRD:DNA substrates (RER). Rnaseh2b-/- MEFs were complemented with Rnaseh1 (+H1), Rnaseh2b (+H2B) or EGFP by retroviral infection. Mean of n=3 independent experiments ± SEM.",
    "ncbi_link": "EGFP: 
RNase H1: 19819
Rnaseh1: 19819
RNase H2B: 67153
Rnaseh2b: 67153"
  },
  {
    "caption": "B, C. DNA damage is reduced to wildtype levels by complementation with Rnaseh2b but not Rnaseh1, measured by 53BP1 foci formation in detergent-extracted fixed cells. (B) Representative images (scale bar, 10 µm). (C) At least 150 cells were counted for each cell line in three independent experiments. Mean ± SEM, **** = p<0.0001 two-tailed t-test.",
    "ncbi_link": "Rnaseh1: 19819
Rnaseh2b: 67153"
  },
  {
    "caption": "B, C. DNA damage is reduced to wildtype levels by complementation with Rnaseh2b but not Rnaseh1, measured by 53BP1 foci formation in detergent-extracted fixed cells. (B) Representative images (scale bar, 10 µm). (C) At least 150 cells were counted for each cell line in three independent experiments. Mean ± SEM, **** = p<0.0001 two-tailed t-test.",
    "ncbi_link": "Rnaseh1: 19819
Rnaseh2b: 67153"
  },
  {
    "caption": "D-F. CCL5 (D) and CXCL10 production (E), as well as ISG induction (F) in Rnaseh2b-/- MEFs are reduced close to wildtype levels (Rnaseh2b+/+), by complementation with Rnaseh2b but not Rnaseh1. Mean of n=6 independent experiments ± SEM for complemented cells; n=3 independent experiments for Rnaseh2b-/- parental and Rnaseh2b+/+ controls cells. * = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001 two-tailed t-test indicates significantly reduced expression compared to Rnaseh2b-/- parental cells.",
    "ncbi_link": "Rnaseh1: 19819
Rnaseh2b: 67153"
  },
  {
    "caption": "D-F. CCL5 (D) and CXCL10 production (E), as well as ISG induction (F) in Rnaseh2b-/- MEFs are reduced close to wildtype levels (Rnaseh2b+/+), by complementation with Rnaseh2b but not Rnaseh1. Mean of n=6 independent experiments ± SEM for complemented cells; n=3 independent experiments for Rnaseh2b-/- parental and Rnaseh2b+/+ controls cells. * = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001 two-tailed t-test indicates significantly reduced expression compared to Rnaseh2b-/- parental cells.",
    "ncbi_link": "Rnaseh1: 19819
Rnaseh2b: 67153"
  },
  {
    "caption": "B. HeLa cells were transfected with FUNDC1-MYC or empty vector for 24 h. Cell lysates were immunoprecipitated by anti-MYC antibody and immunoblotted with indicated antibodies.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "D and E. HeLa cells were transfected with the indicated FUNDC1-MYC constructs for 24 h. Cell lysates were immunoprecipitated using anti-Calnexin and immunoblotted using anti-MYC and anti-Calnexin antibodies.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "F. Immunoblots of subcellular fractions from HeLa cells transfected with scramble siRNA and exposed to hypoxia (1% O2) for 5 h. PNS: post-nuclear supernatant; CYTO: cytosol; ER: endoplasmic reticulum; MITO: mitochondria; MAM: mitochondrial-associated membrane. DRP1 (S) and DRP1 (L) indicate short and long exposures, respectively.G. Immunoblots of subcellular fractions from HeLa cells transfected with Calnexin siRNA (si-CNX) and exposed to hypoxia (1% O2) for 5 h. PNS: post nuclear supernatant; CYTO: cytosol; ER: endoplasmic reticulum; MITO: mitochondria; MAM: mitochondrial-associated membrane. DRP1 (S) and DRP1 (L) indicate short and long exposures, respectively.H. Quantification of the MAM:PNS ratio of FUNDC1 or DRP1 in HeLa cells treated with scramble siRNA or si-CNX and exposed to hypoxia (1% O2) for 5 h. Data are presented as mean ± s.e.m. from 3 independent experiments; *** P < 0.001.",
    "ncbi_link": "CNX: 821"
  },
  {
    "caption": "B. Immunogold electron microscopy of control HeLa cells (top) or HeLa cells transfected with si-FUNDC1 (bottom) and then exposed to hypoxia (1% O2) for 12 h. DRP1 was detected with anti-DRP1 (12 nm gold particles). Blue stars indicate mitochondria. Yellow arrows indicate gold particles. Red arrows indicate double-membraned autophagosomes.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "G. 10-20 g GST-FUNDC1 or GST was immobilized on glutathione sepharose resin (GE Healthcare). 20-50 g DRP1 was incubated with the GST-FUNDC1 or GST bound resin overnight at 4 °C. The resin was then extensively rinsed and eluted. Samples were subjected to SDS-PAGE, and then visualized by coomassie blue staining and western blot, respectively.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "H. Full-length FUNDC1-MYC, FUNDC1-MYC (AA 96-155), FL (Δ129-138) or vector control were transfected with Mito-DsRed (red) into FUNDC1 KD MEFs. 12 h post- transfection, cells were exposed to hypoxia for 12 h and then stained with anti-MYC (blue) and anti-DRP1 (green). Bar = 10 µm. Numbers at the right show the average length of mitochondria in Mito-DsRed-positive cells.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "F. HeLa cells were transfected by different truncated FUNDC1-MYC. About 24h post-transfection, cell lysates were immunoblotted using indicated anti-bodies.",
    "ncbi_link": "FUNDC1: 139341"
  },
  {
    "caption": "D, RT-qPCR time courses. Promoters of the indicated oscillating genes were used to drive expression of a destabilized, nuclear GFP protein from a single copy integrated transgene; gfp mRNA and the endogenous transcript driven by the same promoter were quantified from the same RNA samples. Relative expression was calculated as -dCT = - (target CT values - actin CT values) and then mean normalized for each trace individually. Peak phases (ϕPeak) and amplitudes (A) for the endogenous transcripts are from (Meeuse et al., 2020). qPCR was performed in technical replicate, shown are averages.",
    "ncbi_link": "gfp: 
actin: 179535"
  },
  {
    "caption": "C, Image sequence of an L1 synchronized grh-1::aid animal (HW2418) grown at 20°C on a 250 μM auxin-containing plates. A lethargic animal was transferred to an agar-pad containing microscopy slide and images were collected every 1 sec, using DIC, 100x magnification. Selected images of Movie EV1 are shown. Time stamp (min:sec) is indicated. Arrows indicate phenotypic features: loosening of the cuticle (0:00); back-and-forth movements (0:05); inflation of the cuticle (2:46); vesicles underneath loosened cuticle (6:11); rupturing of the cuticle (6:20, 6:40).",
    "ncbi_link": "grh-1: 190048"
  },
  {
    "caption": "A, Quantification of the percentage of grh-1::aid animals constitutively expressing luciferase (HW2434) that enter each of four molts molt upon hatching into increasing concentrations of auxin as indicated.",
    "ncbi_link": "luciferase: 
grh-1: 190048"
  },
  {
    "caption": "A-D, Heatmaps showing trend-corrected luminescence (Lum, arbitrary units) of grh-1::aid animals constitutively expressing luciferase (HW2434). T = 0h corresponds to time of plating embryos, which subsequently hatch at different times. Arrow indicates time point when 250 μM auxin was added, i.e. prior to the first molt (A; M1), M2 (B), M3 (C) or M4 (D) larval stage. Note that for technical convenience in (A), auxin was provided at time of plating. Animals are sorted by entry into M1 (A), M2 (B), M3 (C), M4 (D), respectively.",
    "ncbi_link": "luciferase: 
grh-1: 190048"
  },
  {
    "caption": "Time-lapse imaging of grh-1::gfp::3xflag animals producing endogenously GFP-tagged GRH-1 protein. Average +/- 95% confidence interval (cyan shading) are shown; gray boxes indicate average time of molts.",
    "ncbi_link": "flag: 
gfp: 
grh-1: 190048"
  },
  {
    "caption": "D, Western blot revealing rapid GRH-1 depletion in the grh-1::aid strain (HW2434) upon addition of 250 µM auxin. A synchronized culture of animals was grown in liquid at 20°C. After 21 h (denoted t=0 h in the figure), the culture was split in two and either auxin or vehicle were added as indicated. Cultures were sampled hourly and protein lysates probed by Western blotting using anti-FLAG and anti-actin antibodies as indicated.",
    "ncbi_link": "grh-1: 190048"
  },
  {
    "caption": "(B) The upper panel showing qRT-PCR analysis of four identified LUAD-associated RBPs (ADARB1, CELF2, QKI and ZFP36) mRNA levels in 61 LUAD tissues and matched paracarcinoma tissues. The lower panel showing relative mRNA expression (T/N) of the four RBPs in metastatic (n = 28) and non-metastatic (n = 33) LUAD tissues. LUAD tissues were classified into metastatic and non-metastatic tissues as described in Materials and Methods. T, LUAD tissues; N, paracarcinoma tissues. Y axis represents the log10 transformed fold change of mRNA expression (T/N) of four RBPs.",
    "ncbi_link": "ADARB1: 104
CELF2: 10659
QKI: 9444
ZFP36: 7538"
  },
  {
    "caption": "(E-G) Kaplan-Meier survival curves of LC, LUAD and LUSC patients (n=1540, n=865 and n=675, respectively) with high or low expression levels of QKI. The log-rank test was used to analyze the difference between two groups.",
    "ncbi_link": "QKI: 9444"
  },
  {
    "caption": "(H) qRT-PCR analysis of endogenous mRNA levels of QKI-5, QKI-6, and QKI-7 in human bronchial epithelial cell line BEAS-2B, LUAD cell lines A549 and H1299.",
    "ncbi_link": "QKI-5: 9444
QKI-6: 9444
QKI-7: 9444"
  },
  {
    "caption": "(J) In vitro RNA pull-down assays were performed using biotin-labeled TGFβR1 3' UTR segments in A549 and H1299 cells. After pull-down, endogenous QKI-5 enrichments were detected by western blot analyses. β-actin was used as the protein control.",
    "ncbi_link": "TGFβR1: 7046"
  },
  {
    "caption": "(A and B) qRT-PCR and western blot analyses of TGFβR1 mRNA and protein levels in QKI-5-overexpressing A549 and H1299 cells. (C and D) Expression of TGFβR1 mRNA and protein in QKI-5-silenced A549 and H1299 cells.",
    "ncbi_link": "QKI-5: 9444
TGFβR1: 7046"
  },
  {
    "caption": "(K) QKI-5-overexpressing A549 and H1299 cells were treated and subjected to qRT-PCR assays to detect the mRNA expression of downstream genes of the TGF-β/SMAD signaling, including PAI-1, Slug, Snail, E-cadherin, and/or N-cadherin.",
    "ncbi_link": "E-cadherin: 999
N-cadherin: 1000
QKI-5: 9444
PAI-1: 5054
Snail: 6615
Slug: 6591"
  },
  {
    "caption": "(C-F) Wound-healing migration assays were performed on QKI-5-overexpressing A549 and H1299 cells as well as control cells The wound healing was recorded (C and E) and quantitatively measured (D and F) at least six times.",
    "ncbi_link": "QKI-5: 9444"
  },
  {
    "caption": "(G and H) In the presence or absence of TGF-β1, QKI-5-overexpressing A549 and H1299 cells were allowed to migrate through a polycarbonate membrane in Transwells. After 24 h, migrated cells were stained, photographed and counted in at least four random fields under a light microscope. Representative images (left) and the migrated cell numbers (right) were presented. (I and J) QKI-5-overexpressing A549 and H1299 cells were treated and allowed to invade through Matrigel-coated membrane in Transwells. Invasive cells were determined",
    "ncbi_link": "QKI-5: 9444"
  },
  {
    "caption": "(E) H&E staining was performed for the evaluation of lung micrometastases. Representative images showing micrometastases of lung tissues from a pair of mice Blue and red arrowheads indicate lung micrometastases of vector group and QKI-5-overexpressing group, respectively. (F) Dot plots showing the difference of the micrometastases counts in lung tissues between QKI-5-overexpressing group and vector control group (n = 10 mice per group). (G) Representative microscopic photographs of H&E staining for liver micrometastases in a pair of mice Blue and red arrowheads indicate liver micrometastases. (H) Dot plots showing the difference of the micrometastases counts in liver tissues between QKI-5-overexpressing group and control vector group (n = 10 mice per group).",
    "ncbi_link": "QKI-5: 9444"
  },
  {
    "caption": "(J) Kaplan-Meier survival curves of LUAD patients (n=865) with high or low expression levels of TGFβR1. The log-rank test was used to compare the difference between two groups.",
    "ncbi_link": "TGFβR1: 7046"
  },
  {
    "caption": "qRT-PCR analyses of mRNA expression of QKI-5 in A549 cells transfected with siRNAs of TFs, which have potential binding sites in QKI-5 promoter.",
    "ncbi_link": "QKI-5: 9444"
  },
  {
    "caption": "(E) Western blot analysis of QKI-5 protein levels in KLF6-silenced A549 cells.",
    "ncbi_link": "KLF6: 1316"
  },
  {
    "caption": "(F) An overview of KLF6-ChIP-seq data (GSE96355) is illustrated using Integrative Genomics Viewer (IGV) software. An obvious peak was detected at position -100 to +100 in the QKI-5 promoter.",
    "ncbi_link": "QKI-5: 9444"
  },
  {
    "caption": "qRT-PCR analysis of KLF6 mRNA in 61 LUAD tissues and matched paracarcinoma tissues (I) T, LUAD tissues; N, paracarcinoma tissues. Y axis represents the log10 transformed fold change of mRNA expression of KLF6. Central dotted line of the violin plot represents median, and upper and lower dotted line represents quartile (I).",
    "ncbi_link": "KLF6: 1316"
  },
  {
    "caption": "A Quantitative RT-PCR (RT-qPCR) results showing relative expression levels of mouse Pabpn1l in somatic tissues, oocytes, and preimplantation embryos. n = 3 biological replicates. Error bars indicate S.E.M.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "C Western blot results of PABPN1L in MII oocytes of wild type (WT) and Pabpn1l−/− females. DDB1 is blotted as a loading control.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "D Cumulative pup numbers of WT and Pabpn1l-/- female mice. n = 5 for each genotype. Error bars, S.E.M. ***P < 0.001 by two-tailed student's t-test.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "E Quantification of preimplantation embryos derived from WT and Pabpn1l-/- females when WT embryos reached the corresponding stages. The number of analyzed embryos is indicated (n). Error bars, S.E.M. ***P < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "F Representative images of the embryos collected from the oviducts of mated WT and Pabpn1l-/- females at the indicated time points after hCG injection. Scale bar = 100 μm.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "A Scatter plot comparing the transcripts of GV oocytes and zygotes from WT and Pabpn1l-/- females. Transcripts that increased or decreased by more than 3-fold in Pabpn1l-deleted GV oocytes or zygotes are highlighted in red or blue, respectively.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "D RT-qPCR results for relative expression levels of the indicated maternal transcripts in oocytes and zygotes from WT and Pabpn1l −/− females. n = 3 biological replicates. Error bars, SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "E Poly(A) tail assay results showing poly(A)-tail length of indicated transcripts in WT and Pabpn1l-deleted oocytes and embryos. The poly(A) tails of Actin are used as an internal control. Each sample was prepared from 100 oocytes or embryos. Plots show the averaged relative signal intensity (y-axis) and length of the PCR products based on mobility (x-axis).",
    "ncbi_link": "Actin: 
Pabpn1l: 382035"
  },
  {
    "caption": "A Scatter plot comparing the transcripts of 2-cell embryos from WT and Pabpn1l-/- females. Transcripts that increased or decreased by more than 3-fold in Pabpn1l-deleted oocytes or embryos are highlighted in red or blue, respectively.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "C 5-Ethynyl uridine (EU) fluorescence (green) showing RNA transcription in WT and Pabpn1l♀−/♂+ 2-cell embryos. Some WT embryos were treated with α-amanitin as early as the zygote stage and cultured to the 2-cell stage. The phosphorylated RNA polymerase II CTD repeat YSPTSPS (pS2) (red) is co-stained to label the RNA polymerase II activity. Nuclei are labeled by DAPI (blue). Scale bar = 20 μm.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "F Representative images of MuERV-L::tdTomato relative to GFP signal in the same embryo when WT embryos reached the corresponding stages. Zygotes were injected with the MuERV-L::tdTomato reporter plasmid and polyadenylated Gfp mRNA (as a positive control of microinjection), then allowed to develop in vitro. Cultured embryos were imaged at 24 h and 40 h after hCG injection. DIC, differential interference contrast. Scale bar = 100 μm.",
    "ncbi_link": "Gfp: 
tdTomato: "
  },
  {
    "caption": "A RNA immunoprecipitation (RIP) results showing the interaction of BTG4 with indicated transcripts, in the presence or absence of PABPN1L (full length, RRM-deleted, or R171A mutant). HeLa cells were co-transfected with plasmids expressing FLAG-tagged PABPN1L and HA-tagged BTG4 for 48 h before immunoprecipitating with an anti-HA antibody. RNAs recovered from the immunoprecipitants were subjected to RT-qPCR of the indicated transcripts. Fold change values of both input and IP samples were normalized by RIP results of HA-BTG4 and FLAG-PABPN1L co-expression groups. n = 3 biological replicates. Error bars, S.E.M. The P-value represents the two-tailed Student's t-test comparing the RIP results of BTG4 with the indicated transcripts in the presence of PABPN1L, *P < 0.05, **P < 0.01, and ***P < 0.001.",
    "ncbi_link": "FLAG: 
HA: 
BTG4: 56057
PABPN1L: 382035"
  },
  {
    "caption": "Co-IP and western blot results showing interactions between PABPN1L and BTG4. Lysates from HeLa cells expressing HA-BTG4 (WT or mutants shown in (B)) and FLAG-PABPN1L were immunoprecipitated with an anti-HA antibody. The immunoprecipitated proteins are detected by western blot with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HA: 
BTG4: 56057
PABPN1L: 382035"
  },
  {
    "caption": "D Co-IP and western blot results showing interactions between PABPN1L and BTG4. Lysates from HeLa cells expressing HA-BTG4 (WT or mutants shown in (B)) and FLAG-PABPN1L were immunoprecipitated with an anti-HA antibody. The immunoprecipitated proteins are detected by western blot with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HA: 
BTG4: 56057
PABPN1L: 382035"
  },
  {
    "caption": "E Diagrams of mouse BTG2 and BTG4 constructs, and co-IP results showing that PABPN1L binds to BTG4 but not BTG2.",
    "ncbi_link": "BTG2: 12227
BTG4: 56057"
  },
  {
    "caption": "F Diagrams and co-IP results showing BTG4 binding to PABPN1L. Lysates from HeLa cells expressing HA-BTG4 and FLAG-PABPN1L (full length and C-terminal deleted) were immunoprecipitated with an anti-FLAG antibody. The immunoprecipitated proteins are detected by western blot with the indicated antibodies.",
    "ncbi_link": "FLAG: 
HA: 
BTG4: 56057
PABPN1L: 382035"
  },
  {
    "caption": "G Diagrams of PABPN1 and PABPN1L constructs, and co-IP results showing that PABPN1L, but not PABPN1, binds to BTG4.",
    "ncbi_link": "PABPN1: 8106
PABPN1L: 382035"
  },
  {
    "caption": "B RT-qPCR results showing the relative expression level changes (MII/GV) of indicated transcripts. Fully grown GV oocytes of Pabpn1l-/- mice were microinjected with mRNAs encoding PABPN1L or BTG4 and were released from meiotic arrest at 12 h after microinjection. Total RNA was extracted from 10 oocytes in each sample. Error bars, S.E.M. *P < 0.05, **P < 0.01, and ***P < 0.001 by two-tailed Student's t-test compared to the first column. ns: non-significant.",
    "ncbi_link": "BTG4: 56057
Pabpn1l: 382035
PABPN1L: 382035"
  },
  {
    "caption": "C Western blot results showing the expression of exogenous PABPN1L (full length, RRM-deleted, or R171A mutants) and BTG4 in Pabpn1l-/- oocytes at the MII stage. The total protein from 100 oocytes is loaded in each lane. pERK1/2 is blotted to indicate the developmental stages. DDB1 is blotted as a loading control. At least three independent experiments were done with consistent results.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "D RNA immunoprecipitation results showing the interaction of PABPN1L with indicated transcripts. Fully grown GV oocytes of WT mice were microinjected with mRNAs encoding PABPN1L (WT, RRM-deleted, or R171A mutant), and were released from meiotic arrest at 12 h after microinjection. Total RNAs were extracted from 350 MI stage oocytes in each sample. RNAs recovered from the immunoprecipitants were subjected to RT-qPCR of the indicated transcripts. Fold change values of both Input and IP samples were normalized by RIP results of the FLAG-PABPN1L microinjection group. Error bars, S.E.M. *P < 0.05, **P < 0.01, and ***P < 0.001 by two-tailed Student's t-test comparing with RNA levels pulled-down by PABPN1L WT in the second column.",
    "ncbi_link": "PABPN1L: 382035"
  },
  {
    "caption": "A Western blot results showing the levels of the indicated proteins in WT and Pabpn1l-/- oocytes. Total protein from 100 oocytes is loaded in each lane. DDB1 is blotted as a loading control.",
    "ncbi_link": "Pabpn1l: 382035"
  },
  {
    "caption": "B HeLa cells were transfected with plasmids expressing HA-BTG4 and FLAG-PABPN1L for 12 h and then treated by cycloheximide (CHX, 10 μM). Cells were harvested at the indicated time points for western blots. DDB1 is a loading control.",
    "ncbi_link": "FLAG: 
HA: 
BTG4: 56057
PABPN1L: 382035"
  },
  {
    "caption": "E Western blot results showing endogenous BTG4 levels in WT and Pabpn1l-/- oocytes at the MII stage. FLAG-PABPN1L was expressed in Pabpn1l-/- oocytes by mRNA microinjected at the GV stage. Total proteins from 100 oocytes are loaded in each lane. ERK1/2 is blotted as a loading control.",
    "ncbi_link": "FLAG: 
Pabpn1l: 382035
PABPN1L: 382035"
  },
  {
    "caption": "(C) Western blot showing that Hel2(1-315) is defective in RQC but not in NGD. The arrest products derived from the R(CGN)12 reporter in ltn1∆ cells expressing truncated Hel2 mutant protein were detected with an anti-GFP antibody.",
    "ncbi_link": "Hel2: 851859
ltn1: 855289"
  },
  {
    "caption": "(D) Northern blot showing the 5' NGD-IM derived from the R(CGN)12 reporter in ski2∆ cells expressing the indicated Hel2 mutant proteins. 5' NGD-IMs were detected with a DIG-labelled GFP probe.",
    "ncbi_link": "Hel2: 851859
ski2: 851114"
  },
  {
    "caption": "(E) Primer extension mapping of 5' ends of 3' NGD-intermediates in Hel2-WT or Hel2(1-315) mutant cells at nucleotide resolution. . The primer extension samples were analysed using 5% TBE-Urea-PAGE and detected by fluorescence. Non-specific reverse transcription (ReTr) products are indicated by asterisks.",
    "ncbi_link": "Hel2: 851859"
  },
  {
    "caption": "(A) Northern blot analysis demonstrating that K63-linked ubiquitination was required for an endonucleolytic cleavage by R(CGN)12. The ski2∆UB-WT and ski2∆ub-K63R cells were transformed with the R(CGN)12 reporter, and total RNA samples were separated by 2% agarose/MOPS gel. 5'NGD-IMs in the cells were detected as in Fig 1D.",
    "ncbi_link": "UB: 
ub: 
ski2: 851114"
  },
  {
    "caption": "(B) Western blot showing that K63-linked ubiquitination was required for RQC. Protein samples from UB-WT, UB-WT ltn1∆, ub-K63R, ub-K63R ltn1∆ cells expressing the GFP-R(CGN)12-HIS3 reporter were subjected to Western blot analysis using an anti-GFP antibody to detect the arrest products. Note the accumulation of RQC-specific CAT-tails in lane 2.",
    "ncbi_link": "UB: 
ub: 
ltn1: 855289"
  },
  {
    "caption": "(C) Western blot analysis demonstrating polyubiquitination of uS10: Affinity-tagged Hel2-Flag-TEV-ProteinA (FTP) was co-purified with ribosomes harbouring HA-tagged wild type uS10 (uS10-3HA ribosomes) or uS10 mutated in its ubiquitination sites (K6/8R). Western blots of whole protein extracts were performed using an anti-HA antibody to detect polyubiquitinated uS10-3HA.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "(F-H) Northern blot analysis of NGD-cleavage sites in the absence of uS10 ubiquitination or RQT complex components: The full-length GFP-R(CGN)12-FLAG-HIS3 mRNA and 5' NGD-intermediates (5' NGD-IM) or 3' NGD-intermediates (3' NGD-IM) were detected in the indicated mutant cells by Northern blotting with DIG-labelled probes. 5' NGD-intermediates were detected by DIG-labelled GFP probe and 3' NGD-intermediates were detected by the DIG-labelled HIS3 probe. SCR1 was used as loading control. FL = full-length. Note the upstream shift of NGD cleavage sites in lanes F4, G4, H6, and H8.",
    "ncbi_link": "GFP: 
HIS3: 
SCR1: 
FLAG: 
uS10: 856371"
  },
  {
    "caption": "(I) Mapping of 5' ends of 3' NGD-intermediates as demonstrated in Fig 1E. Non-specific reverse transcription (ReTr) products are indicated by asterisks. Note that both uS10 ubiquitination and Slh1/Rqt2 were required for an endonucleolytic cleavage within the road-blocked ribosome (X1-X4).",
    "ncbi_link": "uS10: 856371
Rqt2: 853187
Slh1: 853187"
  },
  {
    "caption": "Both RQC and NGDRQC+ are triggered by a (CGA-CCG) dicodon containing arrest sequence in vivo. (C) Northern blot for the 5' NGD-IM derived from the (CGA-CCG) reporter in ski2∆ cells. 5'-NGD-IMs were detected with a DIG-labelled GFP probe. SCR1 was used as a load control.",
    "ncbi_link": "GFP: 
SCR1: 
ski2: 851114"
  },
  {
    "caption": "(D) Western blot of test translations using the (CGA-CCG) dicodon stalling mRNA reporter shown in (A). The mRNA reporter was added to a yeast in vitro translation extract obtained from a ski2∆uS10-3HA strain. Expression of the translation products (free His- and V5 tagged truncated uL4 protein and the same protein attached to tRNA) was visualized with an anti-V5 antibody.",
    "ncbi_link": "uS10: 856371
ski2: 851114"
  },
  {
    "caption": "(A) Western blot analysis after overexpression of Hel2 in strains expressing HA-tagged ribosomal proteins using an anti-HA antibody. Note the increase of the polyubiquitinated eS7 as well as uS10 and uS3.",
    "ncbi_link": "Hel2: 851859"
  },
  {
    "caption": "(C) Western blot analysis showing the role of Hel2 and Not4 in eS7A ubiquitination: Both copies of eS7 (eS7A and eS7B) were deleted and transformed with a plasmid containing HA-tagged eS7A (eS7-WT) or eS7A mutated in the four potential ubiquitination sites (4KR). Whole protein extracts we obtained from eS7AΔeS7BΔ cells or cells with an additional deletion in E3 ligases Hel2 and Not4 (hel2Δ and not4Δ). Note that the four mutated lysine residues were responsible for Not4-dependent monoubiquitination.",
    "ncbi_link": "HA: 
hel2: 851859
Hel2: 851859
not4: 856799
Not4: 856799
eS7A: 854263
eS7: 854263
eS7B: 855628"
  },
  {
    "caption": "(D) Western blot showing that Not4 was required for Hel2-mediated polyubiquitination of eS7 in Hel2-bound ribosomal complexes: Cells expressing HA-tagged eS7A or the eS7-4KR mutant, as well as PTH-tagged Hel2 in eS7AΔeS7BΔ and eS7AΔeS7BΔnot4Δ background were probed for eS7-ubiquitination. Either cell lysates or affinity-purified Hel2-ribosome complexes were used. The levels of the ubiquitinated eS7A in the lysates and in the affinity-purified samples with PTH-Hel2 were determined by Western blot analysis using an anti-HA antibody to detect eS7.",
    "ncbi_link": "not4: 856799
Not4: 856799
eS7A: 854263
eS7: 854263///855628
eS7B: 855628"
  },
  {
    "caption": "(E) Western blotting of in vitro ubiquitination assays of eS7A. The reactions were performed with the indicated components including His-tagged ubiquitin. Ribosomes were purified from Hel2Δ cells expressing HA-tagged eS7A. Polyubiquitinated HA-tagged eS7A (eS7A-3HA) was detected by Western blot analysis using an anti-HA antibody. We observed Hel2-mediated polyubiquitination of the monoubiquitinated eS7A.",
    "ncbi_link": "Hel2: 851859
eS7A: 854263"
  },
  {
    "caption": "(F) Western blot analysis of eS7A in vitro ubiquitination assays showing that Hel2-mediated polyubiquitination of eS7 was mainly K63-linked and required Not4-dependent monoubiquitination: These assays were performed similarly as described in (E) except yeast strains were lacking Not4 (not4Δ). Reactions were performed with the indicated components including His-tagged ubiquitin and several ubiquitin mutants and eS7A-ubiquitination was monitored using an anti-HA antibody.",
    "ncbi_link": "not4: 856799
Not4: 856799"
  },
  {
    "caption": "(A-C) Northern blots probing for the 5' NGD-IM in mutant cells expressing the R(CGN)12 reporter. (A) 5' NGD-IM detection in not4∆ski2∆, hel2∆ski2∆, slh1∆ski2∆, not4∆ slh1∆ski2∆. Quantification of full length and the 5'NGD-IM relative to the loading control (SCR1) is given below. Note the size difference of 5'-NGD IMs resulting from NGDRQC+ and NGDRQC- and that the shorter 5'-NGD intermediate (representing intermediates of the NGDRQC- pathway) was reduced in not4∆slh1∆ski2∆ mutant cells.",
    "ncbi_link": "hel2: 851859
not4: 856799
SCR1: 9164887
ski2: 851114
slh1: 853187"
  },
  {
    "caption": "Northern blots probing for the 5' NGD-IM in mutant cells expressing the R(CGN)12 reporter. (B) Northern blot as in (A) except uS10-WTski2∆ or uS10-K6/8Rski2∆ mutant cells with or without a deletion of Not4 (not4∆) were used. Note that the shorter 5'-NGD intermediates are also reduced in ski2∆not4∆uS10-K6/8R cells.",
    "ncbi_link": "not4: 856799
Not4: 856799
uS10: 856371
ski2: 851114"
  },
  {
    "caption": "Northern blots probing for the 5' NGD-IM in mutant cells expressing the R(CGN)12 reporter. (C) Cells expressing HA-tagged eS7A or the eS7A-4KR mutant in a ski2ΔeS7AΔeS7BΔ or ski2ΔeS7AΔeS7BΔslh1Δ backgrounds were probed for 5'-NGD intermediates by Northern blotting. Note that the four mutated lysine residues in eS7 were responsible for NGDRQC- in the R(CGN)12 reporter.",
    "ncbi_link": "HA: 
eS7A: 854263
eS7: 854263
eS7B: 855628
ski2: 851114
slh1: 853187"
  },
  {
    "caption": "(D) Western blot analysis showing that K83 and K84 of eS7A are main target sites for Hel2 and Not4-mediated ubiquitination: Similarly, as in Fig 6C, eS7AΔeS7BΔ mutant cells were used and wild type and single mutants of HA-tagged eS7A were expressed. Ubiquitinated eS7-HA was monitored using an anti-HA antibody.",
    "ncbi_link": "eS7A: 854263
eS7B: 855628"
  },
  {
    "caption": "(E) Northern Blot analysis probing for the levels of 5' NGD-IM derived from the R(CGN)12 reporter expressed in eS7AΔeS7BΔski2Δ cells and HA-tagged eS7 or eS7 mutants. We observed, that ubiquitination at K83 or K84 of eS7A is mainly responsible for NGDRQC-.",
    "ncbi_link": "HA: 
eS7A: 854263
eS7: 854263
eS7B: 855628
ski2: 851114"
  },
  {
    "caption": "(F) The levels of polyubiquitinated eS7A were increased by the overproduction of wild-type Hel2 (FL) but neither Hel2ΔRING nor Hel2(1-315) mutants. eS7A-3HAhel2Δ mutant cells harbouring the indicated plasmids expressing wild-type Hel2 (FL), Hel2ΔRING or Hel2(1-315) mutant proteins were harvested. Protein samples were analysed by Western blotting with an anti-HA (Top panel) or anti-FLAG antibody (Bottom panel).",
    "ncbi_link": "HA: 
Hel2: 851859
hel2: 851859
eS7A: 854263"
  },
  {
    "caption": "F. RT-PCR analysis of RNA isolated from mouse liver for Birc5, FoxM1B and cyclin B1. Data are presented as log2 fold change and were calculated using non-operated mouse liver tissue as a control. Unpaired, two-tailed Student t-test was used to determine the significance between the log2 values of livers 6, 24 and 48 h post PH compared to the sham operated controls. Log2 values are plotted on a linear scale as mean ± SD.",
    "ncbi_link": "Birc5: 11799
cyclin B1: 268697
FoxM1B: 14235"
  },
  {
    "caption": "B. RT-PCR analysis of RNA isolated from mouse liver for FoxM1B, Birc5 and cyclin B1, Cyclin A2, Cyclin D1 and p21. RT-PCR data are presented as log2 fold change and each value post PH was calculated for each mouse by comparison to its resected liver lobe. Circle, with red outline marks the aged non-regenerating livers shown in Figure 2B. Each dot is representing an independent animal.",
    "ncbi_link": "Birc5: 11799
Cyclin A2: 12428
cyclin B1: 268697
Cyclin D1: 12443
p21: 12575
FoxM1B: 14235"
  },
  {
    "caption": "A. Eight weeks old mice were injected with liposomes coupled to scrambled siRNA (siScr) or sequences targeting MST1 & MST2 (siMST). Each dot is representing an independent animal. The % of Mst1 & Mst2 mRNA remaining in the liver was tested by RT-PCR, 1, 3 and 6 days post injection and calculated compared to control non-transfected livers. Unpaired, two-tailed Student t-test was used to calculate the significance of mRNA remaining in comparison to non-transfected control livers at each time point.",
    "ncbi_link": "MST1: 15235
Mst1: 15235
MST2: 56274
Mst2: 56274"
  },
  {
    "caption": "D. Quantitative RT-PCR analysis of RNA isolated from mouse liver for FoxM1B, Birc5 and cyclin B1, 1, 3 and 6 days post injection. Log2 fold change was calculated using non-transfected mouse liver as control. Unpaired two tailed Student t-test was used to calculate the significance of fold change of in comparison to a panel non-transfected control livers.",
    "ncbi_link": "Birc5: 11799
cyclin B1: 268697
FoxM1B: 14235"
  },
  {
    "caption": "D. Quantitative RT-PCR analysis of RNA isolated from mouse liver for FoxM1B, Birc5 and cyclin B1 at 0 and 40 h post PH. Log2 fold change was calculated using non-transfected/non-resected mouse liver as a control. Representative results of a single experiment with n = 6 animals per group are shown. Paired, two-tailed Student t-test was used to calculate the significant change in signals between liver tissues at the time of resection (0h) compared to 40 h post PH.",
    "ncbi_link": "Birc5: 11799
cyclin B1: 268697
FoxM1B: 14235"
  },
  {
    "caption": "Uncoupled (LEAK) mitochondrial respiration of soleus (SOL) and extensor digitorum longus (EDL) muscle of wild type (WT) vs. Ucp1-TG (TG) mice (WT n=9, TG n=5).",
    "ncbi_link": "Ucp1: 22227"
  },
  {
    "caption": "Multi-tissue transcriptomic profiling of Gdf15 gene expression. Heatmap is shown as raw ct expression values (n=4 per genotype). Quantification of Gdf15 mRNA expression in TG mice is shown as fold change compared to WT littermates (WT n=5, TG n=4).",
    "ncbi_link": "Gdf15: 23886"
  },
  {
    "caption": "Gdf15 gene expression of differentiated C2C12 muscle cells treated with vehicle control (Ctrl) or chemical mitochondrial uncoupler (FCCP, 1µM vs. 5µM) for 5hrs (n=3 biological replicates)",
    "ncbi_link": "Gdf15: 23886"
  },
  {
    "caption": "Genotyping PCR panel of Gdf15 and HSA-Ucp1 loci shown for wild type (WT), Gdf15-KO (KO), Ucp1-TG (TG) and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Relative mRNA expression in quadriceps (Quad) of Ucp1 and Gdf15 in 20wks male WT (n=8), TG (n=7) and TGxKO (n=6) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Body mass (A), body lean mass (B) and body fat mass (C) development. Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Body mass (D), body lean mass (E) and body fat mass (F) during aging at 20wks, 45wks and 95wks of age. Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Subcutaneous white adipose tissue (sWAT) (G) and epididymal white adipose tissue (eWAT) (H) mass development at 10wks, 20wks, 45wks and 95wks of age. Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice at 10wks (WT n=6, TG n=7, TGxKO n=5), 20wks (WT n=10, TG n=10, TGxKO n=10), 45wks (WT n=5, TG n=6, TGxKO n=7) and 95wks (WT n=8, TG n=5, TGxKO n=5).",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Representative H&E histological staining of sWAT at 20wks of age (scale bars represent 50 μm) Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "relative mRNA expression profile in sWAT of male mice (WT n=7, TG n=8, TGxKO n=8) (B). Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Representative immunoblots (C) and quantification (D) of UCP1 protein expression in sWAT of male mice at 20wks of age (WT n=4, TG n=6, TGxKO n=4). Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Relative mRNA expression profile in eWAT (WT n=7, TG n=8, TGxKO n=8). Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Plasma FGF21 levels from male mice at 20wks of age (n=10 per genotype). Plasma Leptin levels from male mice at 20wks of age (n=5 per genotype). Post-absorptive plasma insulin levels at 20wks of age (WT n=8, TG n=9, TG n=9). : Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Blood glucose (I) and insulin levels (J) with total area under the curve (AUC) of insulin (K) during oral glucose tolerance test (oGTT) at 17wks of age (WT n=8, TG n=11, TG n=11). Data are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice.",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Physical activity of male mice shown hourly over 24-hrs and as day and night time. Data shown are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice at 17-18wks of age (WT n=12, TG n=11, TG n=10) and shown as means + SEM",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "energy expenditure of male mice shown hourly over 24-hrs and as day and night time. Data shown are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice at 17-18wks of age (WT n=12, TG n=11, TG n=10) and shown as means + SEM",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": ", total assimilated energy of male mice shown hourly over 24-hrs and as day and night time. Table showing mean values of assimilated energy (kJ) at day/night time and per 24-hrs. Energy balance calculated as delta of assimilated energy (AE) and energy expenditure (EE) and energy balance (J) per 24-hrs. Data shown are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice at 17-18wks of age (WT n=12, TG n=11, TG n=10) and shown as means + SEM",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Respiratory quotient (RQ) shown hourly over 24-hrs (J), RQ amplitude (K) and metabolic flexibility via percentage relative cumulative frequency (PRCF) (L). Data shown are from male wild type (WT), Ucp1-TG (TG), and Ucp1-TGxGdf15-KO (TGxKO) mice at 17-18wks of age (WT n=12, TG n=11, TG n=10) and shown as means + SEM",
    "ncbi_link": "Gdf15: 23886
Ucp1: 22227"
  },
  {
    "caption": "Relative quadriceps (Quad) mRNA expression of the ISR components Atf4, Atf5, Atf6 and Chop (WT day n=9, WT night n=5, TG day n=20, TG night n=12). Data shown are from male wild type (WT) vs. Ucp1-TG (TG) mice sacrificed at day (10am) or night (10pm).",
    "ncbi_link": "Atf4: 11911
Atf5: 107503
Atf6: 226641
Chop: 13198
Ucp1: 22227"
  },
  {
    "caption": "Representative immunoblots of ISR component eIF2α (B) and quantification of phospho-eIF2α (p-eIF2aSer51) relative protein expression (C) in skeletal muscle (Gastroc, WT day n=4, WT night n=5, TG day n=9, TG night n=9). Data shown are from male wild type (WT) vs. Ucp1-TG (TG) mice sacrificed at day (10am) or night (10pm).",
    "ncbi_link": "Ucp1: 22227"
  },
  {
    "caption": "Relative mRNA expression of Rev-erba (D) and Gdf15 (E) in quadriceps, liver and eWAT (WT day n=9, WT night n=5, TG day n=20, TG night n=12). Data shown are from male wild type (WT) vs. Ucp1-TG (TG) mice sacrificed at day (10am) or night (10pm).",
    "ncbi_link": "Gdf15: 23886
Rev-erba: 217166
Ucp1: 22227"
  },
  {
    "caption": "Skeletal muscle (Quad) GDF15 protein content normalized to total protein content (WT day n=4, WT night n=5, TG day n=14, TG night n=12) Circulating GDF15 plasma levels (WT day n=9, WT night n=5, TG day n=18, TG night n=12). Data shown are from male wild type (WT) vs. Ucp1-TG (TG) mice sacrificed at day (10am) or night (10pm).",
    "ncbi_link": "Ucp1: 22227"
  },
  {
    "caption": "(e, f) (e) RIP qPCR and (f) PCR analysis performed using an antibody against endogenous ARID1B. for monitoring NEAT1_2 levels. RIP with NONO and IgG was used as a positive and negative control respectively. GAPDH levels were also assessed in the assay. Data are expressed as a percent of Input.",
    "ncbi_link": "GAPDH: 2597
NEAT1: 283131"
  },
  {
    "caption": "(c) smFISH analysis was performed to detect NEAT1 signal in the nucleus. The scale bar corresponds to 10 µm. Graph showing the FISH signal quantification across the knockdowns in comparison to scramble control. The number of nuclei (n) used for quantification is mentioned.",
    "ncbi_link": "NEAT1: 283131"
  },
  {
    "caption": "A)  Cyclin B2 knock-out and induced degradation by immunoblotting. Indicated cell lines were analysed 24 hours after mock or Dox/IAA/Asv (DIA) treatment using the indicated antibodies to confirm homozygous gene tagging and efficiency of  protein degradation. ( ",
    "ncbi_link": "Cyclin B2: 9133"
  },
  {
    "caption": "(D) Cell proliferation of A2dd, CycB1dd and B1dd/B2ko following mock or DIA treatment. 1000 cells were plated in each well (diameter 3.5cm) and incubated for 10 days before methanol fixation and Crystal Violet staining.",
    "ncbi_link": "A2: 890
B1: 891
CycB1: 891
B2: 9133"
  },
  {
    "caption": "(E) Kinetics  of mitotic entry as measured by time lapse microscopy in A2dd and B1dd/B2ko cells following mock or four-hour DIA treatment of asynchronous cells. The cells were imaged for 16h with 5min intervals using widefield  DIC, mitotic entry was manually scored by detecting cell rounding. Curves display the cumulative mitotic index (data from three repeats, n>500 cells per condition, s. d. indicated by shaded area).",
    "ncbi_link": "A2: 890
B1: 891
B2: 9133"
  },
  {
    "caption": "(I) Cyclin A2  siRNA depletion causes endoreplication. Following 72 hours of siRNA transfection MCF7 and MCF10A cells were analysed by  PI staining and  FACS. The histograms show the changes in  DNA  content (PI Int.) towards >4N following cyclin A2 depletion.",
    "ncbi_link": "Cyclin A2: 890
cyclin A2: 890"
  },
  {
    "caption": "(J) Cyclin A2 siRNA and degron depletion in RPE-1  cells. RPE-1 OsTIR1  and RPE-1 A2dd cells were subjected to 72 hours of cyclin A2 siRNA depletion and/or of DIA treatment as indicated and probed for cyclin A2 levels by  immunoblotting. The longer exposure (L.E.) reveals incomplete depletion of cyclin 2  by siRNA.",
    "ncbi_link": "TIR1: 
A2: 890
Cyclin A2: 890
cyclin A2: 890"
  },
  {
    "caption": "(C) Representative images from  live-cell imaging of SiR-Tubulin labelled (red) mitotic B1dd/B2ko cells expressing FusionRed-H2B (green), Mis12-GFP (white); time in mins, scale bar = 5µm. Cells were imaged four hours after DIA treatment.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(G) Upper panel, confirmation of  Cdc27  depletion by  immunoblotting 72 hours after siRNA transfection in  B1dd/B2ko cells. Lower panel, following 40-hour siRNA transfection B1dd/B2ko cells were treated for 24 hours with Thymidine, released for 10 hours and treated with proTAME and Apcin for additional four hours. At this point, the cells were fixed and  stained with tubulin and pericentrin for  immunofluorescence  analysis.",
    "ncbi_link": "B1: 891
B2: 9133
Cdc27: 996"
  },
  {
    "caption": "(H) Representative images of mitotic spindles in control- and DIA-treated B1dd/B2ko cells following arrest in mitosis by proTAME/Apcin treatment Tubulin staining  is shown in white, pericentrin in green and  DAPI in red, scale bar = 5µm.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(L) Immunofluorescence  images from mitotic Ctr and DIA treated  B1dd/B2ko cells after P/A synchronisation stained with anti-alpha-tubulin (green), anti-gamma-tubulin (red) antibodies and DAPI  (blue), scale bar = 5µm. Cells were exposed to ice-cold medium and either fixed immediately after cold exposure, or incubated for 5,10, or 20 minutes at 37° C before fixation.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(A) Time-lapse  images of PCNA-mRuby tagged  A2dd cells. The imaging sequence was started at the time of Doxycycline addition, and degron activity was triggered three hours later by addition of  IAA  and Asv or PBS (indicated by dashed line). Time is shown as hh:min, scale bar equals 10µm. For further analysis cells were chosen that had dissipated their PCNA foci before the addition of DIA to ensure that cyclin A2 degradation was triggered in G2 phase.",
    "ncbi_link": "A2: 890
cyclin A2: 890"
  },
  {
    "caption": "(D) Images from time-lapse sequence of mitosis showing cell division  in controls and after addition of 0.5µM PD-166285 in DIA treated  A2dd labelled with SiR-DNA (time  is indicated as hh:min, the scale bars represent 20µm).",
    "ncbi_link": "A2: 890"
  },
  {
    "caption": "(D) Cyclin A2dd cells with inducible CycB1-YFP (B1-WT) and  CycB1-YFP-NLS (B1-NLS) were analysed for DIA induced cyclin B1  expression / cyclin A2 depletion. Samples were collected at indicated time points and probed by immunoblotting with cyclin B1  and cyclin A2 antibodies",
    "ncbi_link": "YFP: 
Cyclin A2: 890
CycB1: 891"
  },
  {
    "caption": "(I) Immunoprecipitation of YFP from extract from   A2dd following induction of YFP (Y), CycB1-YFP (BY) and CycB1-YFP-NLS (BYN). The samples in the odd lanes (IAA/Asv-) were treated with 1µg/ml  doxycycline alone, while samples in even lanes (IAA/Asv+) were treated with Auxin and  Asv to induce cyclin A2 depletion. Total cell extract and  immune-precipitates  were probed by immunoblotting with the indicated antisera.",
    "ncbi_link": "A2: 890"
  },
  {
    "caption": "(F) Representative images of  Ki-67 immunofluorescent staining of chromosome  spreads from control (Ctr) and DIA treated P/A synchronised  B1dd/B2ko cells and quantification of Ki-67 staining  intensity using cross-sections of chromosomes",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(G) Representative images from  live-cell imaging  of DIA-treated SiR-Tubulin labelled (red) B1dd/B2ko cells expressing FusionRed-H2B (green) and AurB-GFP  (white); time is indicated in minutes, scale bar = 5µm. Bottom panel shows frequencies of aberrant AurB localisation in P/A synchronised B1dd/B2ko cells.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(J) Tpx2 shows reduced spread on mitotic chromosomes in DIA treated B1dd/B2ko cells. The top panel shows immunofluorescence images, for quantification we measured the mean intensity of Tpx2 staining on the centrosomes and spindle and plotted the ratio of these values per cell. We also analysed the centrosome/spindle distribution of  AurA  that does not change following DIA treatment.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(B) Confirmation of ENSA/ARPP19 S67 phosphorylation in mitotic extracts from Ctr and DIA treated cells, before and after ENSA/ARPP19 siRNA depletion.",
    "ncbi_link": "ARPP19: 10776
ENSA: 2029"
  },
  {
    "caption": "A) Representative images from live-cell imaging of siRNA transfected B1dd/B2ko cells (FusionRed-H2B in red, SiR-Tubulin  in white, scale bar = 10µm). Bar-plot panels on the right show single-cell analysis of 10 cells manually scored for length mitosis pre-NEBD and post-NEBD. Entry into  prophase was scored by cell rounding and NEBD was identified by influx of Tubulin in the  nucleus.",
    "ncbi_link": "B1: 891
B2: 9133"
  },
  {
    "caption": "(B) Widefield Imaging. DIC (Grey), SiR-DNA  (b/w), of ENSA/ARPP19 siRNA transfected DIA treated B1dd/B2ko cells. Time is indicated in hh:min, scale bar = 10µm.",
    "ncbi_link": "ARPP19: 10776
B1: 891
B2: 9133
ENSA: 2029"
  },
  {
    "caption": "(A) Mettl14 cKO leads to perinatal lethality. Newborn cKO pups are smaller with tight and shiny skin.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(C) H/E staining of newborn skin sections from WT and Mettl14 cKO mice.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(A)  EdU staining of WT or Mettl14 cKO skin  after pulse-chase labeling. Skin samples were counterstained with antibody against β4-integrin. Note reduced EdU label-retaining cells in cKO  skin epidermis. Arrows indicate  Edu-positive cells. (B) Label-retaining cells in WT or Mettl14 cKO skin were quantified and shown as box plots. The plot indicates the mean (solid diamond within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=6 (biological repeats), P<0.05 (Student's t-test). n=19, P<0.01 (Student's t-test). ",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(C) Number of holoclones derived from WT and Mettl14 cKO skin was quantified and shown as box and whisker plots. The plot indicates the mean (solid diamond within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=6 (biological repeats), P<0.05 (Student's t-test). n=24, P<0.01 (Student's t-test).",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(D) Morphology  of primary keratinocytes isolated from WT or Mettl14 cKO skin.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(F) Proliferation of WT and Mettl14  null cells in vitro was quantified and shown as dot plots. n=3, P<0.01 (Student's t-test) for Day 6, 9, and 12, and P<0.05 (Student's t-test) for  Day 3. Error bar represents S.D.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(G-H) CFE (colony formation efficiency) of WT and Mettl14 null cells was determined in vitro. Results were quantified and shown as bar graph (F). n=19, P<0.01 (Student's t-test). Error bar represents S.D.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "(I) Fluorescence microscopy demonstrates different  survival capability of WT and Mettl14  inducible KO cells with or without Tamoxifen (TAM) treatment. (J) Ratio of WT and Mettl14  inducible KO cells in the co-culture model was quantified and shown as dot plots. n=8, P<0.01 (Student's t-test) for KO cells with  TAM  treatment compared with WT cells or KO cells without TAM stimulation at both Day 7 and 14. Error bar represents S.D. ",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "C) Deletion of endogenous Pvt1 by an inducible Cas9 (iCas9) system can significantly reduce Pvt1 RNA  level  (quantification from RT-PCR, left panel) and MYC protein level (quantification from  immunoblot, right panel)  expression. n=3, P<0.01 (Student's t-test). Error bar represents S.D.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "D) CFE of WT, Pvt1 inducible KO, and  Pvt1 inducible KO cells rescued with WT or mutant Pvt1 was quantified and presented as bar graph. n=3, **: P<0.01 (Student's t-test). Error bar represents S.D.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "E) Skin organoids derived from WT or Pvt1 inducible KO cells were grafted to nude mice. The regenerated skin was analyzed by  H/E staining.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "F) Epidermal  thickness of WT and  Pvt1  KO skin grafts was quantified and presented as box and whisker plots. The plot indicates the mean (solid diamond within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=6 (biological repeats), P<0.05 (Student's t-test). n=18, P<0.01 (Student's t-test).",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "H)  Fluorescence microscopy  demonstrates different survival capability of WT and Pvt1 inducible KO cells with or without Doxycycline  (Dox) treatment.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "I) Ratio of WT and Pvt1  inducible KO cells in the co-culture model was quantified and shown as dot plots. n=8, P<0.01 (Student's t-test) for KO cells with Dox treatment compared with WT cells or KO cells without Dox stimulation at both Day 7 and 14. Error bar represents S.D.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "A) Interaction between  Pvt1 and MYC was determined by immunoprecipitation followed with RT-PCR. Note significant decrease in Pvt1  and MYC interaction upon  FTO treatment (left panel), calcium shift-induced differentiation (middle panel, Hi: high calcium), and Pvt1 methylation site mutations (right panel). n=3, P<0.01 (Student's t-test). Error bar represents S.D.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "B) Immunoblots show decreased MYC protein level in differentiated  keratinocytes and Mettl14  KO cells.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "Undifferentiated WT and Mettl14 KO cells (C) were treated with cycloheximide. Cell lysates were collected at 0, 30, 60, 90, 120, 180, and 300 minutes post treatment and subjected to  immunoblotting with different antibodies as indicated.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "undifferentiated WT and  Pvt1 KO cells (D) were treated with cycloheximide. Cell lysates were collected at 0, 30, 60, 90, 120, 180, and 300 minutes post treatment and subjected to  immunoblotting with different antibodies as indicated.",
    "ncbi_link": "Pvt1: 19296"
  },
  {
    "caption": "(F)  Skin organoids derived from Mettl14 KO cells or KO cells rescued with exogenous expression of MYC were grafted to nude  mice. The regenerated  skin was analyzed by  H/E staining.",
    "ncbi_link": "Mettl14: 210529
MYC: 4609"
  },
  {
    "caption": "(G) Epidermal  thickness of KO and KO  skin rescued with MYC expression was quantified and presented as box and whisker plots. The plot indicates the mean (solid diamond within the box), 25th percentile (bottom line of the box), median (middle line of the box), 75th percentile (top line of the box), 5th and 95th percentile (whiskers), 1st and 99th percentile (solid triangles) and minimum and maximum measurements (solid squares). n=6 (biological repeats), P<0.05 (Student's t-test). n=18, P<0.01 (Student's t-test).",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(H) Number of p63-positive cells in KO and KO skin rescued with MYC expression was quantified and shown as bar graph. n=5, P<0.01 (Student's t-test). Error bar represents S.D.",
    "ncbi_link": "MYC: 4609"
  },
  {
    "caption": "(I) Fluorescence microscopy demonstrates different survival capability of WT and Mettl14 KO cells with inducible expression of MYC.",
    "ncbi_link": "Mettl14: 210529
MYC: 4609"
  },
  {
    "caption": "(J) Ratio of WT and Mettl14 KO cells with inducible expression of  MYC in the co-culture model was quantified and shown as dot plots. n=8, P<0.01 (Student's t-test) for KO cells without Dox treatment (no  MYC expression) compared with WT cells or KO cells with Dox stimulation (exogenous MYC expression) at both Day 7 and 14. Error bar represents S.D.",
    "ncbi_link": "Mettl14: 210529
MYC: 4609"
  },
  {
    "caption": "(D) Representative photographs of fly eyes and quantitation (below) of rough eye  scores with  fly SRSF1 overexpression (dSF2 OE); n=20-32/genotype. Error bars represent mean +/- SD. Data information: For   eye  scoring, target siRNA lines were compared to non-targeting control siRNA lines using a two-tailed student's t test with Welch's correction for multiple comparisons. ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. Human orthologs of fly  genes are used for labeling.",
    "ncbi_link": "SRSF1: 43912
SF2: 53443"
  },
  {
    "caption": "(F) Quantitation of (GGGGCC)28-EGFP rough eye phenotype  with SRSF modifiers (n > 30  flies/ genotype). Error bars represent mean +/- SD. Data information: For  eye scoring, target siRNA lines were compared to non-targeting control siRNA lines using a two-tailed student's t test with Welch's correction for multiple comparisons. ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. Human orthologs of fly  genes are used for labeling.",
    "ncbi_link": "EGFP: 
SRSF: 53443"
  },
  {
    "caption": "(G) Representative photographs of  fly eyes expressing GMR-GAL4 driven (GGGGCC)28-EGFP  at 29˚C along with the quantifications of necrosis and eye width. n=28-30/genotype. Error bars represent mean +/- SD.",
    "ncbi_link": "EGFP: 
GAL4: "
  },
  {
    "caption": "(H-I) Survival  assays of flies expressing (CGG)90-EGFP under Tub5-GS (H) and ELAV-GS (I) drivers with control or SRSF1  siRNAs. Expression of (CGG)90-EGFP was initiated with addition of drug starting 1 day post eclosion and continued through experiment (Log-rank Mantel-Cox test; n=98-101/genotype for Tub-GS and n=120-141/genotype for  ELAV-GS flies) ∗p < 0.05, ∗∗p < 0.01. (J) Survival assays of (GGGGCC)28-EGFP expressing  fly  under Tub5-GS driver (Log-rank Mantel-Cox test; n=71-93/genotype) with control or SRSF1 siRNAs. ∗∗p < 0.01. ",
    "ncbi_link": "EGFP: 
ELAV: 31000
SRSF1: 43912
Tub: 40554
Tub5: 40554"
  },
  {
    "caption": "(A, B) Representative (A) photographs of  fly eyes  and (B) quantitation with siRNA mediated knockdown of SRPK1 (dSRPK1); n=30-34/genotype. Error bars represent mean +/- SD. Data information: Statistical analysis was performed using two-tailed Student's t test with Welch's correction, ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.",
    "ncbi_link": "SRPK1: 36706"
  },
  {
    "caption": "(C) Representative photographs of fly eyes expressing GMR-GAL4 driven (GGGGCC)28-EGFP  with siRNA mediated knockdown of  SRPK1 or disruption by insertion. (D) Quantitation of rough eye phenotypes. t-test with Welch corrections for comparisons with the control; n= 31-34 flies/ genotype. Error bars represent mean +/- SD. Data information: Statistical analysis was performed using two-tailed Student's t test with Welch's correction, ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.",
    "ncbi_link": "EGFP: 
GAL4: 
SRPK1: 36706"
  },
  {
    "caption": "(E) Representative external eye imaging for detection of GFP aggregates caused by (CGG)90-EGFP transgene expression (top). Converted images used to quantify total intensity of  GFP puncta (bottom). (F) Depletion of SRSF1 or SRPK1 by RNAi results in reduced (CGG)90-EGFP  puncta compared to control siRNA as quantified by total intensity (a.u. = arbitrary unit). n=13-15 flies/genotype. Error bars represent mean +/- SD. Data information: Statistical analysis was performed using two-tailed Student's t test with Welch's correction, ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. ",
    "ncbi_link": "EGFP: 
SRSF1: 43912
SRPK1: 36706"
  },
  {
    "caption": "(B) Anti-FLAG immunoblot of DMSO and SRPIN340 pre-treated HEK293T cells expressing AUG-nLuc-3xFLAG control or CGG-nLuc-3xFLAG RAN translation reporters. β-Actin is used as a loading control. To prevent signal saturation, AUG-nLuc lysate was diluted 1:3 in sample buffer prior to loading (n=3 biological replicates). Schematics of the AUG-nLUC-3xFLAG and +1CGG(100)-nLuc-3xFLAG reporters presented on top. Data information: Error bars represent mean +/- SD. Statistical analysis was performed using two-tailed Student's t test with Welch's correction. ∗p < 0.05; ∗∗p < 0.01, ∗∗∗p < 0.001 and ∗∗∗∗p < 0.0001. To prevent over-exposure, the AUG-nLuc lysate was diluted 1:3 in sample buffer.",
    "ncbi_link": "FLAG: 
Luc: 
LUC: "
  },
  {
    "caption": "(D) Anti-FLAG immunoblot  of DMSO  and SRPIN340 pre-treated HEK293T cells expressing GGGGCC-nLuc-3xFLAG (GA70) and +2CGG-nLuc-3xFLAG (FMRpolyA) RAN translation reporters (n=3 biological replicates). Schematics of the GA70 (GGGGCCx70) and +2CGG reporters presented on top. Data information: Error bars represent mean +/- SD. Statistical analysis was performed using two-tailed Student's t test with Welch's correction. ∗p < 0.05; ∗∗p < 0.01, ∗∗∗p < 0.001 and ∗∗∗∗p < 0.0001.",
    "ncbi_link": "FLAG: 
Luc: 
FMR: 2332"
  },
  {
    "caption": "(E) Immunoblot of DMSO and SPHINX31 pre-treated  HEK293T cells expressing AUG-nLuc-3xFLAG control or CGG-nLuc-3xFLAG RAN translation reporters. (n=3 biological replicates). (F) Anti-FLAG of DMSO and SPHINX31 pre-treated HEK293T cells expressing  GGGGCC-nLuc-3xFLAG (GA70) and +2CGG-nLuc-3xFLAG (FMRpolyA) RAN translation reporters (n=3 biological replicates). Data information: Error bars represent mean +/- SD. Statistical analysis was performed using two-tailed Student's t test with Welch's correction. ∗p < 0.05; ∗∗p < 0.01, ∗∗∗p < 0.001 and ∗∗∗∗p < 0.0001. ",
    "ncbi_link": "FLAG: 
Luc: 
FMR: 2332"
  },
  {
    "caption": "(C, D) Expression of GGGGCC-nLuc-3xFLAG (C) and +2CGG-nLuc-3xFLAG (D) RAN translation reporters in HEK293T  cells treated with 2 μM TG (for stress induction) analyzed by immunoblot  (n=3 biological replicates). To evaluate effects of  SRPK1 inhibition cells were pre-treated with  DMSO or SRPIN340 before reporter transfection. Data information: Error bars represent mean +/- SD. Two-tailed Student's t test with Welch's correction. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 and ∗∗∗∗p < 0.0001.",
    "ncbi_link": "FLAG: 
Luc: "
  },
  {
    "caption": "(D) Anti-FLAG immunoblot blot  of DMSO  and SRPIN340 pre-treated HEK293T cells transfected with in vitro transcribed CGG-nLuc-3xFLAG reporter RNA. β-Actin is used as a loading control. Error bars represent mean +/- SD (n=6 biological replicates). Statistical analysis was performed using Student's t test with Welch's correction. ∗p < 0.05",
    "ncbi_link": "FLAG: 
Luc: "
  },
  {
    "caption": "(A, B) Pharmacological targeting of SPRK1 with (A) 40 μM SRPIN340  or (B) 8 μM SPHINX31 reduced the cumulative risk of death in +1(CGG)100-EGFP (encoding  FMRpolyG) expressing neurons. n= # of  neurons quantified for each condition; Cox proportional hazard analysis, ∗∗∗p < 0.001.",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "(A-B) Proteins and RNA samples of colon tissue were extracted from mice with the indicated treatments. (B) mRNA expression levels of IL-6, IL-12p35 and IL-23p19 were assessed by quantitative RT-PCR and normalized to TBP (n=4-6). Results represent two or more independent experiments.",
    "ncbi_link": "TBP: 
IL-12p35: 16159
IL-23p19: 83430
IL-6: 16193"
  },
  {
    "caption": "(C) Real-time PCR analysis showing mRNA expression levels of IL-6, IL-12p35 and IL-23p19 of FACS isolated monocytes collected from mice with the indicated treatments. Data are obtained from two to three independent experiments (n=6-7 mice pooled per group).",
    "ncbi_link": "IL-12p35: 16159
IL-23p19: 83430
IL-6: 16193"
  },
  {
    "caption": " C Raptor-depleted, WT cortical neurons were imaged by 2P-FLIM before and 30 minutes after treatment with insulin. Inhibiting mTORC1 by depleting Raptor with shRNA made mitochondria insensitive to insulin. Shown here are average data from 4 fields of view of a single replicate out of a total of 3 replicates. Western blots are representative of 3 independent assays. Statistical analyses were performed using Student's two-tailed unpaired t-test ",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": " C Reducing Bcl-xL expression in WT mouse cortical neurons does not affect NiMA. Western blots are representative of 3 independent assays. Statistical analyses were performed using Student's two-tailed unpaired t-test ",
    "ncbi_link": "Bcl-xL: 12048"
  },
  {
    "caption": "C WT mouse cortical neurons expressing either Flag-Raptor H-Ras25 or Flag-Raptor Rheb15 were serum-starved in AβO-containing Hank\"s balanced salt solution for 2 hours. Next, the cells were pulse-labeled for 3 hours with EdU. Note that forcing mTORC1 to the plasma membrane (Flag-Raptor H-Ras25) yielded an ~80% increase in EdU incorporation into mtDNA in the presence of AβOs regardless of whether or not the neurons had been stimulated with insulin+R+L. In contrast, EdU uptake into mitochondrial replisomes was not stimulated by AβOs in neurons whose mTORC1 was forced to lysosomes (Flag-Raptor-Rheb15). Error bars represent ±",
    "ncbi_link": "H-Ras25: 15461
Rheb15: 19744
Raptor: 74370"
  },
  {
    "caption": " A Unmodified ReNcell VM human neuronal progenitor cells were co-plated with comparable Ren-GFP or Ren-APPSL cells into 3-dimensional Matrigel matrices, and differentiated into neurons for 60 days. Cytosolic GFP is produced by both Ren-GFP and Ren-APPSL cells, and the latter also produce pathogenic human APP with the Swedish and London mutations, and secrete Aβ that becomes entrapped in the Matrige Following neuronal differentiation, 2P-FLIM was used to monitor NiMA in the ReNcell VM neurons, which were discriminated from Ren-GFP and Ren-APPSL neurons because they lack GFP. Note that NiMA was observed in ReNcell VM neurons when they were co-cultured with Ren-GFP neurons, but not when they were co-cultured with Ren-APPSL neurons. Each colored line refers to a single field of view containing 5-15 cells, and each pair of solid and dotted lines of the same color refers to the same field of view. Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "APP: 
APPSL: 351"
  },
  {
    "caption": " B ReNcell VM cells were differentiated into neurons for 30 days in 2D cultures. Subsequent AβO exposure for 16 hours blocked NiMA, but expression of Flag-Raptor-Rheb15, which forces mTORC1 to lysosomes, prevented NiMA inhibition by AβOs. Each colored line refers to a single field of view containing 5-15 cells, and each identically colored pair of solid and dotted lines refers to the same field of view. Flag-Raptor -Rheb15 expression was confirmed by western blot­ting. Statistical analyses were performed using Student's two-tailed unpaired t-test. Western blots are representative of 3 independent assays",
    "ncbi_link": "Rheb15: 6009
Raptor: 57521"
  },
  {
    "caption": " A Cortical mouse neurons from tau knockout (KO) mice were serum-starved in Hank's balanced salt solution for 2 hours. The cells were then imaged for NiMA, after which insulin or amino acids were immediately added, and the cells were then imaged again 30 minutes later Data information: Each colored lin refers to a single field of view containing 2-15 cells, and each pair of solid and dotted lines (same color) refers to the same field of view. Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": " B Cortical mouse neurons from tau KO mice were treated with AβOs for 18 hours before being serum-starved in AβO-containing Hank's balanced salt solution for 2 hours. The cells were then imaged for NiMA, after which insulin was immediately added, and the cells were then imaged again 30 minutes later. Note that NiMA occurred in the absence or presence of AβOs, which inhibited NiMA in wild type human neuron Data information: Each colored lin refers to a single field of view containing 2-15 cells, and each pair of solid and dotted lines (same color) refers to the same field of view. Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "tau: 17762"
  },
  {
    "caption": "Wild type mouse cortical neurons depleted of Nprl with shRNA had mitochondria that were insensitive to amino acids (R+L Each colored line refers to a single field of view containing 5-15 cells, and each pair of solid and dotted lines (same color) refers to the same field of view. Knockdown efficiency was monitored by western blotting of phosphorylated ribosomal S6 protein, a downstream target of the mTORC1-S6K pathway. Western blots are representative of 3 independent assays. Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "Nprl: 17168"
  },
  {
    "caption": "Wild type mouse cortical neurons depleted o Tsc2 with shRNA had mitochondria tha were insensitive t insuli Each colored line refers to a single field of view containing 5-15 cells, and each pair of solid and dotted lines (same color) refers to the same field of view. Knockdown efficiency was monitored by western blotting of phosphorylated ribosomal S6 protein, a downstream target of the mTORC1-S6K pathway. Western blots are representative of 3 independent assays. Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "Tsc2: 22084"
  },
  {
    "caption": "(D Human fibroblasts deficient in Tsc2 (TSC2 Δexons1-14) were imaged before and 30 minutes after insulin addition. Lack of Tsc2 made mitochondria insensitive to insulin Cultures were serum-starved in Hank's balanced salt solution for 2 hours before stimulation with insulin or amino acids, and were imaged before and 30 minutes after stimulation. Each colored line refers to a single field of view containing 2-5 cells, and each pair of solid and dotted lines of the same color refers to the same field of view Statistical analyses were performed using Student's two-tailed unpaired t-test",
    "ncbi_link": "Tsc2: 7249
TSC2: 7249"
  },
  {
    "caption": "(E) Re-expression of human Tsc2 rescues mitochondrial responses to insulin. Cultures were serum-starved in Hank's balanced salt solution for 2 hours before stimulation with insulin or amino acids, and were imaged before and 30 minutes after stimulation. Each colored line refers to a single field of view containing 2-5 cells, and each pair of solid and dotted lines of the same color refers to the same field of view. Re-expression of the Flag-WT Tsc2 was corroborated by indirect immun­o­fluorescence (IF). Statistical analyses were performed using Student's two-tailed unpaired t-test ",
    "ncbi_link": "Tsc2: 7249"
  },
  {
    "caption": "(A) Path-seq profiles of desA1, desA2 in MTB infected BMDMs. Error bars show the standard deviation from three biological samples. Representative results from two experiments are presented.",
    "ncbi_link": "desA1: 885444
desA2: 885339"
  },
  {
    "caption": "(B) Upper panel: dissolved oxygen curve over 120 h time course showing controlled depletion (1), sustained hypoxia (2) and controlled reaeration (3). Points represent the average of three biological replicates and were measured via fiber optic technology that non-invasively probes oxygen levels in the culture (PreSens Precision Sensing GmbH). Lower panel: expression profiles (RNA-seq) of desA1 and desA2 over the time course and oxygen levels. Error bars show the standard deviation from three biological samples.",
    "ncbi_link": "desA1: 885444
desA2: 885339"
  },
  {
    "caption": "(C) Rv0681 regulon genes differentially expressed in vitro and the evidence for predicted high Rv0681 activity (induced expression of target genes). (D) Zur regulon genes differentially expressed in vitro and the evidence for decreased Zur activity (de-represses target genes). (E) Rv0691c regulon genes differentially expressed in vitro and in vivo; evidence for increased Rv0691c activity (increased up- and down-regulation of target genes) at 24 h from both in vitro and in vivo infection.",
    "ncbi_link": "Rv0681: 888239
Rv0691c: 888296
Zur: 886009"
  },
  {
    "caption": "(B) Plot of read pile-ups from MSM with inducible overexpression of MSMEG_0916 shows ChIP-binding in the promoters of desA1 and desA2.",
    "ncbi_link": "MSMEG_0916: 4531289
desA2: 4532334
desA1: 4533322"
  },
  {
    "caption": "Boxplots representing RPKM values from RNA-seq of MSM with inducible overexpression of MSMEG_0916. Significant log2 fold change (FC) between uninduced (-ATc) and induced (+ATc) samples for MSMEG_0916 (log2 FC = 4.99), desA1 (log2 FC = -1.32) and desA2 (log2 FC = -1.8) with multiple hypothesis adjusted P-values < 0.0001. Data is from three biological samples (induced) and nine biological samples (uninduced).",
    "ncbi_link": "MSMEG_0916: 4531289
desA2: 4532334
desA1: 4533322"
  },
  {
    "caption": "(A) Serial ten-fold dilutions of MTB H37Rv wild type (wt) and MTB with inducible overexpression of Rv0472c were spotted on 7H10 agar plates with or without ATc.",
    "ncbi_link": "Rv0472c: 886308"
  },
  {
    "caption": "(B) Argentation TLC of 14C-labeled methyl esters of mycolic acids (MAMEs) obtained from apolar lipids and delipidated cell wall fractions of MSM wt and MSM with inducible overexpression of MSMEG_0916. The α, αʹ, epoxy (e) and cyclopropanated α- (X1) MAMES species are labeled. Faster-migrating species that co-migrated with α-MAMES and accumulate with induced MSMEG_0916 overexpression are indicated as X2 and X3.",
    "ncbi_link": "MSMEG_0916: 4531289"
  },
  {
    "caption": "(C) BCG wt and BCG with inducible overexpression of Rv0472c cultures, labeled with 14C-acetate, were induced (+ATc) or uninduced (-ATc) for 4 h or 8 h. The total FAMEs and MAMEs were extracted and analyzed by autoradiography-TLC using equal counts (15,000 cpm) for each lane.",
    "ncbi_link": "Rv0472c: 886308"
  },
  {
    "caption": "(A) Quantitative analysis of the Aβ1-40 protein in the TBS (*p=0.0212), Triton-X (p=0.0544) and SDS (**p=0.0063) fractions of brain homogenates from male (n=7) and female (n=10) APP23 mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(B) Stereological analysis of cortical area covered by 4G8-positive plaques in male (n=10) and female (n=8) APP23 mice (left) and representative images (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, ***p=0.0004.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(C) Fluorescence intensity based analysis of pFTAA-stained Aβ plaques in the cortex of male (n=10) and female (n=8) APP23 mice (left) and representative images (right), scale bar = 1 mm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, **p=0.0011.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(D) Stereological analysis of cortical area covered by Congo Red-positive plaques in male (n=10) and female (n=8) APP23 mice (left) and representative images (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, ***p=0.0001.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(E) Native filter assay analysis of TBS (p=0.2453), Triton-X (p=0.0604), SDS (*p=0.0196) and formic acid (FA) (**p=0.0057) fractions from male (n=8) and female (n=7) APP23 mouse brain homogenates. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test between the same fractions. Data points were taken from graphs analysing APP23p40+/+ against APP23p40-/- mice.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(A) Histological analysis of plaque-associated BACE1 immunoreactivity in male (n=10) and female (n=8) APP23 mice. BACE1 area covered was normalised to 4G8-positive area covered of the same image (left). Right: representative images, scale bar = 50 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.3724.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(B) Stereological quantification of the number of cortical GFAP-positive astrocytes in male (n=10) and female (n=8) APP23 mice (left). Right: representative images of GFAP staining, scale bar = 200 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, *p=0.0134.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(C) Quantification of activated microglia within 30 µm from plaque borders. Top: Numbers of Iba1-positive microglia were normalised to the size of the nearest 4G8-positive plaque and quantified in male (n=10) and female (n=8) APP23 mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.0576. Bottom: Histogram representing Clec7a staining intensity within plaque-associated Iba1-positive microglia in male (n=10) and female (n=8) APP23 mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for each single bin, p=N.S.. Right: representative images, scale bar = 40 µm. Data points were taken from graphs analysing APP23p40+/+ against APP23p40-/- mice.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(D) Radial intensity profiles of Iba1 and 4G8 around the center of the nucleus of plaque-associated Iba1-positive microglia in male (n=10) and female (n=8) APP23 mice. Iba1 intensity declines until a radius of ~6 µm, marking the cell periphery. 4G8 intensity peaks inside the cell (~4 µm), but stays high outside the cell. This is very likely due to the close proximity to 4G8 positive plaques. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for the number of binned radii shows no significant difference between both 4G8 traces.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "(A) Gene expression analysis of IL12b in whole brain (n=3 per gender, Il12b undetected), Cd11b-negative non-microglial cells (n=3 per gender, Il12b undetected) and CD11b-positive microglia (n=5 per gender, p=0.3540) in male and female APP23 mice. Gapdh expression was used as an internal reference gene. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test for each fraction.",
    "ncbi_link": "APP: 351
Gapdh: 14433
IL12b: 16160
Il12b: 16160
Cd11b: 16409
CD11b: 16409"
  },
  {
    "caption": "(B) ELISA measurements of the IL12p40 concentration in the TBS-soluble protein fraction derived from wild-type (WT) (n=5), APP23p40+/+(n=17) and APP23p40‑/- (n=16) mice. Male mice are depicted by blue squares while female mice are shown as red squares. Mean ± s.e.m., statistical analysis: one-way ANOVA, Tukey post-hoc test, *p=0.0276, ***p=<0.0001.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(A) Mesoscale analysis for the Aβ1-40 protein in the TBS (p=0.2298), Triton-X (p=0.1329) and SDS (p=0.7184) fractions of brain homogenates from male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice. Total protein concentration of each sample was used as an internal reference. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(B) Stereological analysis of cortical area covered by 4G8-positive plaques (left) and representative images of 4G8-staining in APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, **p=0.0039.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(C) Fluorescence intensity based analysis of pFTAA-positive area covered in the cortex of APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice (left) and representative images for each genotype (right), scale bar = 1 mm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, **p=0.0051.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(D) Stereological analysis of cortical area covered by Congo Red-positive plaques in APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice (left) and representative images (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, **p=0.0070.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(E) Native filter assay analysis of TBS (p=0.7124), Triton-X (p=0.3170), SDS (p=0.4833) and formic acid (FA) (p=0.8144) fractions from APP23p40+/+ (n=8) and APP23p40-/- (n=8) mouse brain homogenates. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test between the same fractions.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(A) Histological analysis of plaque-associated BACE1 immunoreactivity in male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice. BACE1 area covered was normalised to 4G8-positive area covered of the same image (left). Right: representative images, scale bar = 50 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.1780.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(B) Stereological quantification of the number of cortical GFAP-positive astrocytes in male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice (left). Right: representative images of GFAP staining, scale bar = 200 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.3148.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(C) Quantification of activated microglia within 30 µm from plaque borders. Top: Numbers of Iba1-positive microglia were normalised to the size of the nearest 4G8-positive plaque and quantified in male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.1925. Bottom: Histogram representing Clec7a staining intensity within plaque-associated Iba1-positive microglia in male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for each single bin, p=N.S.. Right: representative images, scale bar = 40 µm.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(D) Radial intensity profiles of Iba1 and 4G8 around the center of the nucleus of plaque-associated Iba1-positive microglia in male APP23p40+/+ (n=10) and APP23p40-/- (n=8) mice. Iba1 intensity declines until a radius of ~6 µm, marking the cell periphery. 4G8 intensity peaks inside the cell (~4 µm), but stays high outside the cell. This is very likely due to the close proximity to 4G8 positive plaques. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for the number of binned radii shows no significant difference between both 4G8 traces.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(A) Mesoscale analysis for the Aβ1-40 protein in the TBS (*p=0.0208), Triton-X (*p=0.0440) and SDS (p=0.0540) fractions of brain homogenates from APP23p40+/+(n=7) and APP23p40-/- (n=8) mice. Total protein concentration of each sample was used as an internal reference. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(B) Stereological analysis of cortical area covered by 4G8-positive plaques (left) and representative images of 4G8-staining in APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.1831.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(C) Fluorescence intensity based analysis of pFTAA-positive area covered in the cortex of APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice (left) and representative images for each genotype (right), scale bar = 1 mm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.3406.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(D) Stereological analysis of cortical area covered by Congo Red-positive plaques in APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice (left) and representative images (right), scale bar = 500 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.4542.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(E) Native filter assay analysis of TBS (p=0.6823), Triton-X (p=0.1146), SDS (p=0.0508) and formic acid (FA) (p=0.6603) fractions from APP23p40+/+ (n=7) and APP23p40-/- (n=7) mouse brain homogenates. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-tests between the same fractions.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(A) Histological analysis of plaque-associated BACE1 immunoreactivity in female APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice. BACE1 area covered was normalised to 4G8-positive area covered of the same image (left). Right: representative images, scale bar = 50 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.5402.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(B) Stereological quantification of the number of cortical GFAP-positive astrocytes in female APP23p40+/+ (n=8) and APP23p40-/- (n=8) mice (left). Right: representative images of GFAP staining, scale bar = 200 µm. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.1579.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(C) Quantification of activated microglia within 30 µm from plaque borders. Top: Numbers of Iba1-positive microglia were normalised to the size of the nearest 4G8-positive plaque and quantified in female APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test, p=0.8240. Bottom: Histogram representing Clec7a staining intensity within plaque-associated Iba1-positive microglia in female APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for each single bin, p=N.S.. Right: representative images, scale bar = 40 µm.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "(D) Radial intensity profiles of Iba1 and 4G8 around the center of the nucleus of plaque-associated Iba1-positive microglia in female APP23p40+/+ (n=8) and APP23p40-/- (n=10) mice. Iba1 intensity declines until a radius of ~6 µm, marking the cell periphery. 4G8 intensity peaks inside the cell (~4 µm), but stays high outside the cell. This is very likely due to the close proximity to 4G8 positive plaques. Mean ± s.e.m., statistical analysis: two-tailed unpaired t-test with Bonferroni correction for the number of binned radii shows no significant difference between both 4G8 traces.",
    "ncbi_link": "APP: 351
p40: 16160"
  },
  {
    "caption": "C AdipoR1 siRNA-transfected ORS or DP cells were treated with APN or P5. The cell lysates were analyzed for p-AMPK.",
    "ncbi_link": "AdipoR1: 51094"
  },
  {
    "caption": "D-H The relative gene expression levels of growth factors in P5-treated DP cells (n = 4 (VEGF, PDGFA), 5 (IGF1), 6 (HGF, FGF7) biological replicates / group)",
    "ncbi_link": "FGF7: 2252
HGF: 3082
IGF1: 3479
PDGFA: 5154
VEGF: 2277///7424///7422///7423"
  },
  {
    "caption": "G H&E and IF for versican of skin tissue; scale bars: 100 µm. H Anagen induction scores of vehicle-, or P5- treated Adipoq-/- mice (n = 6 tissues / mice, 4 mice / group); Unpaired t test ",
    "ncbi_link": "Adipoq: 11450"
  },
  {
    "caption": "K. H&E and IF for versican of skin tissue; scale bars: 100 µm. L Anagen induction scores of vehicle-, or P5- treated Adipor1-/-mice (n = 6 tissues / mice, 5 mice / group); Unpaired t test ",
    "ncbi_link": "Adipor1: 72674"
  },
  {
    "caption": "(G) HeLa GFP-LC3 cells were transfected with control siRNA, CLEC12A siRNA1, or CLEC12A siRNA2 as well as CLEC12A rescue constructs (R1 or R2) and infected for 1 hr with DsRed-labeled Salmonella. Data are shown as mean ± SD; n = 75 per condition. Data are representative of three independent experiments.",
    "ncbi_link": "CLEC12A: 160364"
  },
  {
    "caption": "(H) HeLa cells from (G) were lysed, and HA-CLEC12A expression levels were assessed by western blot. Data are representative of three independent experiments.",
    "ncbi_link": "CLEC12A: 160364"
  },
  {
    "caption": "(A) Representative epifluorescent images showing impaired antibacterial autophagy in ATG16L1 KO HeLa cells complemented with the indicated ATG16L1 protein in the presence of control siRNA or CLEC12A siRNA. The scale bars represent 10 μm. (B) Percentage of LC3-Salmonella colocalization in WT HeLa cells, ATG16L1 KO HeLa cells, and ATG16L1 KO HeLa cells stably expressing ATG16L1∗300T or ∗300A alleles in the presence of control siRNA or CLEC12A siRNA. Data are shown as means ± SD; n = 75. Data shown are representative of three independent experiments.",
    "ncbi_link": "ATG16L1: 55054
CLEC12A: 160364"
  },
  {
    "caption": "(A) Confocal micrographs of LC3-Listeria colocalization in WT and Clec12a−/− BMDMs at 1 hr post-infection. The scale bars represent 10 μm. (B) Quantification of LC3-Listeria colocalization in WT and Clec12a−/− BMDMs. Data shown represent mean ± SD of n = 3 independent experiments; unpaired t test. ∗∗p < 0.01.",
    "ncbi_link": "Clec12a: 232413"
  },
  {
    "caption": "(C and D) Salmonella cfus quantified per gram of stool (C) and per organ (D) at 4 days post-infection are displayed. Data are shown as mean ± SD; ∗∗p ≤ 0.01. Data are representative of at least two independent experiments (n = 9 for WT; n = 7 or 8 for Clec12a−/−).",
    "ncbi_link": "Clec12a: 232413"
  },
  {
    "caption": "(E) Clinical score for infected mice at 4 days post-infection. Data are shown as mean ± SD. Data are representative of at least two independent experiments. ∗∗∗∗p < 0.0001; unpaired t test. (n = 14 for WT; n = 13 for Clec12a−/−).",
    "ncbi_link": "Clec12a: 232413"
  },
  {
    "caption": "(F) Survival curve for infected WT and Clec12a−/− mice (n = 9 mice per genotype).",
    "ncbi_link": "Clec12a: 232413"
  },
  {
    "caption": "(E) Representative epifluorescent images of HeLa cells transfected with a control siRNA or a siRNA against CLEC12A and infected with DsRed-labeled Salmonella for 1 hr. (F) Quantitation of ubiquitin-bacteria colocalization at 1 hr post-infection in cells shown in (E). Data are shown as means ± SEM from three independent experiments.",
    "ncbi_link": "CLEC12A: 160364"
  },
  {
    "caption": "(F) Gentamicin protection assay in HeLa cells showing increased intracellular bacterial replication after 48 hr of knockdown of ATG16L1, KLHL9, NEDD8, or KLHL13. Data shown as mean ± SD; n = 4. Data are representative of three independent experiments.",
    "ncbi_link": "ATG16L1: 55054
KLHL13: 90293
KLHL9: 55958
NEDD8: 4738"
  },
  {
    "caption": "B-K. Transmission electron microscopy (TEM) images of 5 week old adult retinas showing the overall structure of groups of ommatidia in (B) wild type; (C) ADAM17-/- mutant; (D) ADAM17-/Deficiency; (E, F) RNAi against ADAM17 and control (lacZ), expressed throughout the retina; (G, H) RNAi against ADAM17 and control (lacZ), expressed in the neurons; (I,J) RNAi against ADAM17 and control (lacZ), expressed in the pigmented glial cells; and (K) a kuz-/- mutant.",
    "ncbi_link": "kuz: 34772
lacZ: 945006
ADAM17: 43558"
  },
  {
    "caption": "A-C. TEM images of 1day old adult retinas showing the overall structure of clusters of ommatidia (A1, B1, C1), or a single ommatidium (A2, B2, C2) in wild type (A1, A2), ADAM17-/- mutant (B1, B2) or ADAM17-/Df (C1, C2). Red arrows show lipid droplets in PGCs, green shading highlights PGCs. Scale bars for A2, B2 and C2: 2μm and 10μm for all other panels.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "D-J. Fluorescent images of 1 day old fly retinas stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and the photoreceptor membranes respectively; (D) wild type; (E) ADAM17-/- mutant; (F) ADAM17-/ Deficiency; (G) knockdown of ADAM17 throughout the retina; (H) knockdown in glial cells; (I) knockdown in neurons; and (J) kuz-/-; n=10 fly retinas. Scale bars 10μm",
    "ncbi_link": "kuz: 34772
ADAM17: 43558"
  },
  {
    "caption": "M-N. Q-PCR analysis of mRNA transcripts of lipogenic genes -Acetyl CoA carboxylase (ACC) and Fatty Acid Synthase (FASN) from heads of wild type and ADAM17-/- mutants; n=4 and n=3 biological replicates for M and N respectively, with 3 technical replicates for each genotype. The box end points are the upper (75%) and lower (25%) quartiles, the whiskers define the maximum 95th percentile and minimum 5th percentile values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. ***p<0.001, **p<0.01.",
    "ncbi_link": "ACC: 35761
Acetyl CoA carboxylase: 35761
FASN: 33524
Fatty Acid Synthase: 33524
ADAM17: 43558"
  },
  {
    "caption": "A-D. Fluorescent images of 1 day old retinas, stained with BODIPY (green) and FM-dye (red) to stain lipid droplets and the photoreceptor membranes respectively; (A) wild type; (B) ADAM17-/- mutant; (C) overexpression of lipase in glial cells of ADAM17-/- mutant; (D) overexpression of lipase in neurons of ADAM17-/- mutant. Scale bars: 10μm.",
    "ncbi_link": "lipase: 39611
ADAM17: 43558"
  },
  {
    "caption": "H-K. TEM images of 5 week old adult retinas corresponding to (H) wildtype; (I) ADAM17-/- mutant; (J) glial overexpression of lipase in wild-type glial cells; (K) neuronal overexpression of lipase in the ADAM17-/-mutant. Scale bars: 10μm.",
    "ncbi_link": "lipase: 39611
ADAM17: 43558"
  },
  {
    "caption": "A. Alkaline phosphatase (AP)-shedding assays performed for Eiger in S2R+ cells expressing either GFP, Drosophila ADAM17, or activity dead mutants of Drosophila ADAM17, in the presence of either PMA, or PMA and TAPI-1 (DMSO is used as control; see methods); n=5. The box end points are the upper (75%) and lower (25%) quartiles, the whiskers define the maximum 95th percentile and minimum 5th percentile values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. ***p<0.001, **p<0.01.",
    "ncbi_link": "GFP: 
Eiger: 36054
ADAM17: 43558"
  },
  {
    "caption": "E-H. Fluorescent images of 1week old adult fly retinas, stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and photoreceptor membranes respectively: (E) wild type; (F) eiger-/-; (G) grindelwald-/-; (H) wengen-/-. Scale bars: 10μm.",
    "ncbi_link": "eiger: 36054
grindelwald: 35103
wengen: 32849"
  },
  {
    "caption": "J-K. mRNA level transcripts of ACC and FASN measured from head lysates of one week old wild type, eiger-/- and grindelwald-/- . n=3 biological replicates, with 3 technical replicates for each genotype. The box end points represent the maximum and minimum values respectively, the central band is the median and the square is the mean Data were quantified for significance using Student's t test. ***p<0.001, **p<0.01.",
    "ncbi_link": "ACC: 35761
eiger: 36054
FASN: 33524
grindelwald: 35103"
  },
  {
    "caption": "L-O. TEM images of two week old retinas corresponding to (L) control; (M) eiger-/-; (N) grindelwald-/-; (O) wengen-/-. n=180 ommatidia from 3 different fly retinas for each. Scale bars: 10μm.",
    "ncbi_link": "eiger: 36054
grindelwald: 35103
wengen: 32849"
  },
  {
    "caption": "A-D. Fluorescent images of 1 day old adult fly retinas, stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and photoreceptor membranes respectively: (A, B) wild type; (C, D) ADAM17-/- mutants, reared either on DMSO or AD4. Scale bars: 10μm.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "F-I. TEM images of 2 week aged retinas corresponding to either wildtype or ADAM17-/- mutants grown on either DMSO or AD4. Scale bars: 10μm.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "K-N. Fluorescent images of 1 day old adult fly retinas, stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and photoreceptor membranes respectively: (K) ADAM17-/- ; (L) glial specific SOD2 over-expression in an ADAM17-/- mutant; (M) glial specific SOD1 over-expression in an ADAM17-/- mutant; (N) neuronal specific SOD2 overexpression in ADAM17-/- mutant. Scale bars: 10μm.",
    "ncbi_link": "SOD1: 39251
SOD2: 36878
ADAM17: 43558"
  },
  {
    "caption": "P-Q. TEM analysis of 5 week aged retinas corresponding to either ADAM17-/- mutants or SOD2 over-expression in an ADAM17-/- mutant. Scale bars: 10μm.",
    "ncbi_link": "SOD2: 36878
ADAM17: 43558"
  },
  {
    "caption": "R. Percentage of normal, abnormal and missing rhabdomeres in ADAM17-/- mutant retinas, as compared to retinas overexpressing glial specific SOD2 in an ADAM17-/- mutant background observed with TEM; n=180 ommatidia from 3 different fly retinas for each.",
    "ncbi_link": "SOD2: 36878
ADAM17: 43558"
  },
  {
    "caption": "S. Oxyblot analysis of oxidative modification of proteins from retina lysates of wild type and ADAM17-/-. T. Analysis of Oxyblot intensity normalised to its respective actin controls for each genotype. n=3 biological replicates, with 3 technical replicates for each genotype. The box end points represent the maximum and minimum values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. **p<0.01. Scale bars: 10μm.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "A-B. Fluorescent images of 1 day old adult fly retinas, stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and photoreceptor membranes respectively: (A) wild type; (B) ADAM17-/-, both reared in the dark. Scale bars: 10μm.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "C-F. TEM images of 4 week old retinas: (C, D) wildtype, or (E, F) ADAM17-/- flies reared from first larval instar either in total light (C, E) or total dark (D, F). Scale bars: 10μm.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "I. Measurement of MDA levels (in nmoles) from 1 day old retinas of wild type or ADAM17-/- , reared either in light or dark. Four biological replicates with 3 technical replicates for each genotype. The box end points represent the upper (75%) and lower (25%) quartiles, the whiskers define the maximum 95th percentile and minimum 5th percentile values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. **p<0.01.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "J. mRNA levels of the puckered transcripts from retinas of untreated or AD4 treated wild type and ADAM17-/- mutant retinas. n=3 biological replicates, with 3 technical replicates for each genotype. The box end points represent the maximum and minimum values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. **p<0.01.",
    "ncbi_link": "puckered: 40958
ADAM17: 43558"
  },
  {
    "caption": "K-L. Fluorescent images of 1 day old adult fly retinas, stained with BODIPY (green) and FM-dye (red) to mark lipid droplets and photoreceptor membranes respectively: (K) heterozygous mutant of bsk alone; or (L) in combination with ADAM17-/-. Scale bars: 10μm.",
    "ncbi_link": "bsk: 44801
ADAM17: 43558"
  },
  {
    "caption": "M. Quantitation of the BODIPY signal shown as integrated total lipid for the genotypes mentioned in K-L, along with w1118 and ADAM17-/-. n=10 flies per genotype. The box end points represent the upper (75%) and lower (25%) quartiles, the whiskers define the maximum 95th percentile and minimum 5th percentile values respectively, the central band is the median and the square is the mean. Data were quantified for significance using Student's t test. **p<0.01.",
    "ncbi_link": "ADAM17: 43558"
  },
  {
    "caption": "N-O. TEM images of 2 week old adult retinas, showing clusters of ommatidia for a heterozygous mutant of bsk alone (M) or in combination with ADAM17-/- (N); n=3 for each. Scale bars: 10μm.",
    "ncbi_link": "bsk: 44801
ADAM17: 43558"
  },
  {
    "caption": "F-G. Q-PCR analysis of mRNA transcripts of lipogenic genes FASN and LDLR in pooled data obtained from 3 different donors of human iPSC derived microglia treated with either DMSO, GW or GI for 24 hours. n=3 biological replicates, with 3 technical replicates for each genotype. The box end points represent the maximum and minimum values respectively, the central band is the median and the square is the mean. all data were quantified for significance using Student's t test. ***p<0.001, **p<0.01, *p<0.05.",
    "ncbi_link": "FASN: 2194
LDLR: 3949"
  },
  {
    "caption": ", C. siRNA-mediated knockdown of EXOSC10 (EXO10), but not of DIS3 and DIS3L, significantly increased generation of poly-GA in HeLa cells expressing (G4C2) 80 repeats. ctrl\" indicates a control vector which lacks the G4C2 repeat but still contains the 5' flanking region and 3xTAG.",
    "ncbi_link": "DIS3: 22894
DIS3L: 115752
EXO10: 5394
EXOSC10: 5394"
  },
  {
    "caption": ". Increased G4C2 repeat RNA expression upon EXOSC10 knockdown on RT-qPCR.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "E, F. Knockdown of EXOSC10 increased RNA foci in HeLa cells expressing (G4C2) 80 repeats visualized by in situ hybridization targeting sense RNA foci. In total 25 (Ct) and 24 (EXO10#5) images were analyzed in 3 independent experiments. G. Knockdown of EXOSC10 increased RNA foci intensity in HeLa cells expressing (G4C2) 80 repeats. Each dot represents average cellular RNA foci intensity (Arbitrary unit) of RNA foci-positive cells in each randomly taken image. In total 25 (Ct) and 24 (EXO10#5) images were analyzed in 3 independent experiments.",
    "ncbi_link": "EXO10: 5394
EXOSC10: 5394"
  },
  {
    "caption": "A, B. Dose-dependent suppression of poly-GA by exogenous EXOSC10 upon EXOSC10 knockdown.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "C. Suppression of G4C2 repeat RNA by exogenous EXOSC10 on EXOSC10 knockdown. Concentration of transfected EXOSC10 plasmid was 0.2 ng/μl in 1 ml medium.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "D. Overexpression of EXOSC10 decreases G4C2 repeat RNA.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "A, B. Under transcription inhibition with Actinomycin D, cells with EXOSC10 knockdown (EXO10 KD) showed more stable expression of the repeat RNA compared to cells with control knockdown with non-targeting siRNA (Ct KD).",
    "ncbi_link": "EXO10: 5394
EXOSC10: 5394"
  },
  {
    "caption": "C, D. Degradation of FAM-labeled synthetic (G4C2)8 repeat RNA with recombinant human EXOSC10 (hEXO10) (Upper left). 3' blocked FAM-labeled G4C2 repeat RNA resisting 3' exoribonuclease activity is not degraded by recombinant EXOSC10 (Lower left). Lack of recombinant EXOSC10 (Upper right) or Mg2+ ion which is essential co-factor of EXOSC10 (Lower right) abolished the RNA degradation activity. 3 or 4 independent experiments. Quantification of the top bands are shown in (D).",
    "ncbi_link": "EXO10: 5394
EXOSC10: 5394"
  },
  {
    "caption": "E, F. Degradation of antisense C4G2 repeat RNA substrate with recombinant human EXOSC10 (Left). Without recombinant EXOSC10, no substrate degradation was observed (Right). 5 or 6 independent experiments. Quantification is shown in (F).",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "A. In situ hybridization. G4C2 RNA foci were detected in a C9 patient-derived fibroblast but not in a control-derived fibroblast with non-targeting siRNA treatment (left panels, control/si Ct. middle panels, C9/si Ct). Knockdown of EXSOC10 increased RNA foci (right panels, C9/siEXOSC10#5). Nuclei were stained with DAPI (blue). White arrows indicate nuclear RNA foci. The green arrows show cytoplasmic RNA foci.",
    "ncbi_link": "EXOSC10: 5394
EXSOC10: 5394"
  },
  {
    "caption": "B. Quantification of %cell with G4C2 RNA foci. 3 independent knockdown experiments were performed. 10 DAPI positive cells per experiment were randomly selected and z-stack images were obtained. In total, z-stack images from 90 cells per group (control siRNA or EXOSC10 siRNA) were counted for RNA foci. C. Quantification of the number of G4C2 RNA foci/cell. 3 independent knockdown experiments were performed. 10 DAPI positive cells per experiment were randomly selected and z-stack images were obtained. In total, z-stack images from 90 cells per group (control siRNA or EXOSC10 siRNA) were counted for RNA foci. D. Quantification of %cell with C4G2 RNA foci. 3 independent knockdown experiments were performed. 10 DAPI positive cells per experiment were randomly selected and z-stack images were obtained. In total, z-stack images from 90 cells per group (control siRNA or EXOSC10 siRNA) were counted for RNA foci. E. Quantification of the number of C4G2 RNA foci/cell. 3 independent knockdown experiments were performed. 10 DAPI positive cells per experiment were randomly selected and z-stack images were obtained. In total, z-stack images from 90 cells per group (control siRNA or EXOSC10 siRNA) were counted for RNA foci. ",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "F, G. Increased endogenous repeat RNA expression upon EXOSC10 knockdown in strand specific RT-qPCR. 10 independent knockdown experiments (Case1 N=4, Case2 N=4, Case3 N=2) were performed.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "A, B, C. Double knockdown of EXOSC10 and DIS3 significantly increased poly-GA and repeat RNA expression compared with single knockdown of EXOSC10 in cells expressing (G4C2) 80 repeats.",
    "ncbi_link": "DIS3: 22894
EXOSC10: 5394"
  },
  {
    "caption": "D. Overexpression of DIS3 compensated EXOSC10 knockdown-induced repeat RNA accumulation.",
    "ncbi_link": "DIS3: 22894
EXOSC10: 5394"
  },
  {
    "caption": "E, F. Catalytically dead mutant EXOSC10 rescued EXOSC10 knockdown-induced GA increase.",
    "ncbi_link": "EXOSC10: 5394"
  },
  {
    "caption": "B, C. Increased expression of 3'extended snoRA48 precursor upon EXOSC10 knockdown (B) or GFP-poly-GR177/ GFP-poly-PR166 expression (C) on RT-qPCR. D, E. Increased expression of 3'extended snoRA68 precursor upon EXOSC10 knockdown (D) or GFP-poly-GR177 /GFP-poly-PR166 expressions (E) on RT-qPCR.",
    "ncbi_link": "GFP: 
EXOSC10: 5394
snoRA48: 652965
snoRA68: 26780"
  },
  {
    "caption": "F. RT-qPCR analysis showed increased cellular G4C2 repeat RNA expression from co-transfected EF1 (G4C2)80 repeat construct in the presence of GFP, GFP-poly-GR177 or GFP-poly-PR166.",
    "ncbi_link": "EF1: 
GFP: "
  },
  {
    "caption": " (B) Genotyping of KLF4loxp/loxp coupled AAV-Cre inducible mouse. 2x1011 particles of AAV7-Cre-mCherry or AAV7-mCherry were intraperitoneally injected into KLF4 loxp/loxp mice (6~8 weeks). Five weeks later, mice tails were cut and collected for DNA extraction and PCR analysis. PCR results were analyzed by 1% agarose gel. ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " Validation of inducible knockout of KLF4 in mouse intestine. Five weeks after injection of AAV7-Cre-mCherry, mouse intestine was removed and followed by the preparation of tissue section. The KLF4 expression in the intestine was then detected by Western blot ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " Validation of inducible knockout of KLF4 in mouse intestine. Five weeks after injection of AAV7-Cre-mCherry, mouse intestine was removed and followed by the preparation of tissue section. The KLF4 expression in the intestine was then detected by immunohistochemistry ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " (E) Kaplan-Meier survival curves of KLF4 loxp/loxp mice with intraperitoneal injection of AAV7-Cre-mCherry or AAV7-mCherry followed by the treatment with 8-Gy (total-body) γ-irradiation 5-weeks after then. AAV7-mCherry, n=10 per group; AAV7-Cre-mCherry, n=12 per group. p = 0.0023, log-rank test. ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " (F) Histological analysis of intestinal epithelium of KLF4 loxp/loxp mice with AAV7-mCherry or AAV7-Cre-mCherry intraperitoneal injection followed by 8-Gy (total-body) γ-irradiation 5-weeks after then. Tissues were collected from the sham mice and mice at different time after exposure to γ-irradiation. Scale bars, 100 μm. ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " (G-H) Immunofluorescent staining of γ-H2AX, 53BP1 and Cleaved Caspase-3 in the intestinal epithelium of KLF4 loxp/loxp mice with injection of AAV7-mCherry or AAV7-Cre-mCherry followed by treatment of γ-irradiation. Tissues were collected from sham mice and mice at different time after exposure to γ-irradiation and then staining with indicated antibodies. (G) Quantification of γ-H2AX, 53BP1 and active Caspase-3 -positive cells based on the Immunofluorescent staining results presented in H. Data are mean ± SEM; n=4 per group; p = 0.0023 (r-H2AX), p = 7.9x10-4 (53BP1) p = 5.5x10-3 (Active Caspase-3). one-way ANOVA was used for the statistical analysis. Scale bars, 60 μm. ",
    "ncbi_link": "Cre: 
mCherry: 
KLF4: 16600"
  },
  {
    "caption": " (A). Purification of KLF4 protein complex in the presence and absence of DNA damage based on TAP-KLF4 stable expression cells (U2OS). Proteins that interacted with KLF4 were purified from U2OS cells expressing FLAG and HA-tagged KLF4 in the absence and presence of 5 Gy radiation at 4h after the treatment. The accumulated bind induced in response to radiation was isolated for mass spectrometry analysis. PARP1 was identified as a binding partner for KLF4. ",
    "ncbi_link": "FLAG: 
HA: 
TAP: 
KLF4: 9314"
  },
  {
    "caption": " (C). The purified complex was further confirmed by Western blot detected by FLAG-KLF4, PARP1(lane 1). The interaction between KLF4 and PARP1 was significantly increased in response to γ-radiation detected by pulldown experiment (lane 3 and 4). ",
    "ncbi_link": "FLAG: 
KLF4: 9314"
  },
  {
    "caption": " (D) Validation of interaction between ectopically expressed KLF4 and PARP1. 293T cells were transfected with FLAG-KLF4 and Myc-PARP. Whole cell lysates or IP complex pulled down by anti-FLAG antibody were analyzed by Western blotting. ",
    "ncbi_link": "FLAG: 
Myc: 
KLF4: 9314
PARP: 142"
  },
  {
    "caption": " (F) Co-immunoprecipitation of PARP1 with endogenous KLF4 is independent on DNA. The DNA binding inhibitor EtBr was added to the MDA-MB-231 cell lyses followed by immunoprecipitation of KLF4 complex. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " ectopic expressed GFP-PARP1 and DsRed-KLF4 in MDA-MB-231 cells. PARP1 and KLF4 are co-localized in the nucleus, and this co-localization is increased by in response to radiation. Scale bars, 5 μm. ",
    "ncbi_link": "DsRed: 
GFP: 
KLF4: 9314
PARP1: 142"
  },
  {
    "caption": " (L) Loss of PARP1 attenuates KLF4 PARylation. PARP1+/+ and PARP1-/- MEFs cells were transfected with FLAG-KLF4 followed by 4h after 5 Gy radiation, and then the PARylation of KLF4 was detected by pulldown. ",
    "ncbi_link": "FLAG: 
KLF4: 9314
PARP1: 11545"
  },
  {
    "caption": "(D). Identification of amino acid stretch 411- 441 on the Zinc 2 domain of KLF4 involved in mediating its PARylation modification in 293T cells.. PARylation for Flag tagged KLF4 deletion mutants were analyzed, respectively, by pulldown using PAR antibody followed by Western blotting using antibody against Flag.",
    "ncbi_link": "Flag: 
KLF4: 9314"
  },
  {
    "caption": "(E) Dissection of the PARylation region of KLF4 into three zinc finger motif-containing domains, Zinc 1, Zinc 2 and Zinc 3. While no effect was observed on Zinc 1 and Zinc 3 domains, deletion of Zinc 2 domain led to significant attenuation of KLF4 PARylation.",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "(G) Identification of amino acid stretch 829-1014 on the C-terminal segment of PARP1 to be involved in mediating its interaction with KLF4 in 293T cells.",
    "ncbi_link": "KLF4: 9314
PARP1: 142"
  },
  {
    "caption": "(B) The effect of YYR motif mutations on KLF4 PARylation. Constructs of KLF4-Zinc 1-YKH/AAA mutation, KLF4-Zinc 2-YYR/AAA mutation and KLF4-Zinc-2-Y451A mutation were co-transfected with Myc-PARP1 into 293T cells, respectively, and then pulled-down using M2 agarose followed by measuring KLF4 PARylation with anti-PAR antibody.",
    "ncbi_link": "Myc: 
KLF4: 9314
PARP1: 142"
  },
  {
    "caption": " (C) KLF4-Zinc 2-YYR/AAA mutation has only effect on KLF4 PARylation but not on other types posttranslational modifications such as protein methylation, ubiquitylation, acetylation and sumoylation in 293T cells. The FLAG-tagged wild-type or mutant KLF4 were immunoprecipitated with FLAG and detected by anti-SYM10 (methylation), anti-SUMO (sumoylation), Anti-ac-lysine (acetylation), anti-Ub (ubiquitination) and anti-PAR (PARylation). ",
    "ncbi_link": "FLAG: 
KLF4: 9314"
  },
  {
    "caption": " (F) KLF4-Zinc 2-YYR/AAA mutation remarkably reduces DNA damage-induced chromatin recruitment of ectopic expressed KLF4 in U2OS cells. ORC2 is the loading control for chromatid fraction. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (G). Confocal analysis of PAR and FLAG-tagged KLF4 showing that KLF4-Zinc 2-YYR/AAA mutation significantly reduces KLF4 PARylation in U2OS cells. Scale bars, 10 μm. ",
    "ncbi_link": "FLAG: 
KLF4: 9314"
  },
  {
    "caption": " (I) The effect of PARP1 mutations (H909A or T824A) on KLF4 PARylation, confirming the critical role of H909 in mediating KLF4 PARylation in 293T cells. Myc-PARP1 wildtype or mutations (H909A or T824A) and FLAG-KLF4 were co-transfected into 293T cells and then the FLAG-KLF4 was pulldown by anti-FLAG antibody, the PARylation modification of KLF4 was blotted with anti-PAR antibody, and the binding PARP1 was blotted with anti-myc antibody. ",
    "ncbi_link": "FLAG: 
Myc: 
KLF4: 9314
PARP1: 142"
  },
  {
    "caption": " (J). Replacement of this histidine by alanine on PARP1 or replacement of the YYR motif of KLF4 by triple alanines leads to the attenuation of KLF4 PARylation. In PARP1-/- MEFs, wild-type or mutant PARP1 (H909A) were co-transfected with FLAG-tagged wild-type or KLF4-Zinc 2-YYR/AAA mutation followed by immunoprecipitation using M2-agarose and Western blotting by anti-PAR antibody. ",
    "ncbi_link": "FLAG: 
KLF4: 9314
PARP1: 11545"
  },
  {
    "caption": " (K) KLF4 PARylation enhances its transcriptional function demonstrated by p21 promoter luciferase assay. 293T cells were co-transfected with p21 luciferase reporter plasmid with wild-type or mutant KLF4 (YYR/AAA) and wild-type or mutant PARP1 (H909A) and then submitted to luciferase assay. n=3, p=4.74x10-6 (PARP1WT vs PARP1H909A), Data are mean ± SEM; one-way ANOVA was used for the statistical analysis. ",
    "ncbi_link": "luciferase: 
p21: 1026
KLF4: 9314
PARP1: 142"
  },
  {
    "caption": "(A) Depletion of KLF4 directly diminishes the DNA damage-induced p21 expression, resulting in the failure of cell cycle arrest in MDA-MB-231 cells.",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (B) Abolishment of KLF4 PARylation disrupts KLF4-mediated p21 expression that in turn impairs DNA damage response in MDA-MB-231 cells. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "(C) p-H3 staining analysis of KLF4+/+, KLF4-/- MEFs, KLF4-/- MEF with transfection of wild-type or KLF4-Zinc 2-YYR/AAA mutation. n=4, p values were labeled in figure, one-way ANOVA assay.",
    "ncbi_link": "KLF4: 16600
KLF4: 9314"
  },
  {
    "caption": " (D Abolishment of KLF4 PARylation leads to failure in removing damaged DNA as measured by 53BP1 foci. n=4, p=4.74x10-6 (KLF4WT vs KLF4YYR/AAA), one-way ANOVA assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Abolishment of KLF4 PARylation leads to failure in removing damaged DNA as measured by 53BP1 foci. n=4, p=4.74x10-6 (KLF4WT vs KLF4YYR/AAA), one-way ANOVA assay. (E) Summary of D. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (F) Failure of KLF4 PARylation leads to increased aneuploidy population in U2OS cells. n=3, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "(G) Effect of KLF4 PARylation on NHEJ and HR. Wild-type or KLF4-Zinc 2-YYR/AAA mutant KLF4 were co-transfected with I-SCE construction in U2Os-GFP-EJ5 cells (for NHEJ assay) or U2Os-DR-GFP (for HR assay). n=3, p values were labeled in figure, one-way ANOVA assay.",
    "ncbi_link": "GFP: 
KLF4: 9314
I-SCE: 854590"
  },
  {
    "caption": "The effect of overexpression or knockdown KLF4 on mRNA levels of BRCA1 in KLF4-/- MEF n=3, p values were labeled in figures, one-way ANOVA assay.",
    "ncbi_link": "BRCA1: 12189
KLF4: 9314
KLF4: 16600"
  },
  {
    "caption": " The effect of overexpression or knockdown KLF4 on mRNA levels of BRCA1 in MDA-MB-468 n=3, p values were labeled in figures, one-way ANOVA assay. ",
    "ncbi_link": "BRCA1: 672
KLF4: 9314"
  },
  {
    "caption": " The effect of overexpression or knockdown KLF4 on mRNA levels of BRCA1 in MDA-MB-231 n=3, p values were labeled in figures, one-way ANOVA assay. ",
    "ncbi_link": "BRCA1: 672
KLF4: 9314"
  },
  {
    "caption": " (K) Heatmap of BRCA1, P21, Bax expression on U2OS cells with expression of wild-type KLF4 or KLF4-Zinc 2-YYR/AAA mutant as well as KLF4-Zinc 2 (Zinc 2 domain deletion) mutant. No difference of BRCA1 expression was measured between expression of wild-type KLF4 or KLF4-Zinc 2-YYR/AAA mutant, while loss of Zinc domain causes drops of BRCA1 expression levels. ",
    "ncbi_link": "Bax: 581
BRCA1: 672
P21: 1026
KLF4: 9314"
  },
  {
    "caption": " (L) In early responsive window (1-2 hours after exposure to γ-radiation), while elevation of wild-type KLF4 enhances the expression levels of p21, disruption of KLF4 PARylation diminishes KLF4-mediated p21 accumulation. Upon DNA damage, no matter PARylation or not, elevation of both wild-type or KLF4-PARylation-deficient mutant leads to BRCA1 accumulation suggesting the KLF4-mediated regulation of BRCA1 is independent of PARP1 in MDA-MB-231 cells. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "(M) KLF4 physically interacts with BRCA1 upstream promoter region measured by CHIP-PCR.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(N) inset, top, schematic diagram of the BRCA1 promoter and relative positions of primer sets used in this study. ChIP analysis at the BRCA1 promoter using KLF4-specific or nonspecific control IgG (α-Gal4) in MDA-MB-231 cells. Shown is the enrichment at positions of the BRCA1 locus relative to the TSS, presented as percent recovery of input.",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": "(O) inset, top, schematic diagram of the BRCA1 promoter cloning primer and the alignment of potential KLF4 binding motif on BRCA1 promoter with KLF4 binding motif on p21 and SLC5A6 promoter. Shown is the wild-type (BRCA1-WT) or mutant (BRCA1-AA) BRCA1 promoter luciferase reporter activity when co-transfect with KLF4 plasmids. KLF4 co-transfection promotes BRCA1-WT but not BRCA1-AA promoter reporter transcription. n=3, p=0.018, one-way ANOVA assay.",
    "ncbi_link": "BRCA1: 672
p21: 1026
KLF4: 9314
SLC5A6: 8884"
  },
  {
    "caption": " (P) ChIP analysis of KLF4 binding to the BRCA1 promoter in MDA-MB-231 at -.3K positions relative to the TSS in untreated and Olaparib (10µM for 8h) or 5Gy radiation treat cells. No significant difference of KLF4 binds to BRCA1 promoter between untreated and Olaparib or radiation treat cells. n=3, p=0.80, one-way ANOVA assay. ",
    "ncbi_link": "BRCA1: 672"
  },
  {
    "caption": " (Q) BRCA1 reporter assay in KLF4-/- MEFs, KLF4-/- MEF with transfection of wild-type (KLF4WT) or mutant KLF4 (KLF4YYR/AAA, KLF4C403A and KLF4ΔZinc2). The depleted the zinc domain or mutated zinc finger (KLF4C403A and KLF4ΔZinc2) on KLF4 impairs the KLF4-driven BRCA1 expression, while no effect was observed between wild-type and KLF4YYR/AAA mutant. n=3, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "BRCA1: 672
KLF4: 16600
KLF4: 9314"
  },
  {
    "caption": " (R) HR analysis. U2OS-DR-GFP cells were transfected with I-SceI, BRCA1 and siBRCA1 in KLF4-wild-type and depletion condition, respectively. GFP positive cells representing HR repair rate were measured by flow cytometry 48-72 hour after then. Overexpression of BRCA1 restores the HR efficiency in KLF4 knockdown cells. Data are mean ± SEM; n=3, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "GFP: 
BRCA1: 672
KLF4: 9314
I-SceI: 854590"
  },
  {
    "caption": " (A) KLF4+/+, KLF4-/- MEFs, KLF4-/- MEF with wild-type KLF4 or KLF4-Zinc 2-YYR/AAA mutant were treated with 5-10 µM cisplatin for 48 hours followed by measuring the expression of PARP1, p21 and Bax. Loss of PARylation on KLF4 impairs KLF4-mediated inhibition of apoptosis in the presence of genotoxic stress. ",
    "ncbi_link": "KLF4: 16600
KLF4: 9314"
  },
  {
    "caption": " (B) The apoptotic response in U2OS cells with expression of wild-type and mutant KLF4. U2Os cells with wildtype (pLenti-tet-on-KLF4WT) or mutant (pLenti-tet-on-KLF4YYR/AAA) KLF4 were incubated with 10 ng/ml doxycycline for 24h and then treated with 10uM doxorubicin (Dox) or cisplatin (CDDP) for additional 24h. While expression of wild-type KLF4 decreases Bax expression and inhibits drug-induced PARP1 cleavage, expression of PARylation-deficient KLF4 leads to failure in inhibiting genotoxic-induced Bax expression and PARP1 cleavage. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (C) Disruption of KLF4 PARylation leads to failure in inhibiting temperature-induced senescence in BTR model (RAS V12 -induced senescence). ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "Disruption of KLF4 PARylation abolishes the KLF4-promoted cellular transformation in MDA-MB-231 measured by soft agar analysis. n=3, p values were labeled in figure, one-way ANOVA assay.",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Disruption of KLF4 PARylation abolishes the KLF4-promoted cellular transformation in MCF10A measured by soft agar analysis. n=3, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Disruption of KLF4 PARylation abolishes the KLF4-promoted cellular transformation in U2OS measured by soft agar analysis. n=3, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": "KLF4 sensitizes cell to Olaparib. The asterisk in the panels represents the significant difference (p<0.05). (G) The representative of MEFs clonogenic assay.",
    "ncbi_link": "KLF4: 16600"
  },
  {
    "caption": "KLF4 sensitizes cell to Olaparib. The asterisk in the panels represents the significant difference (p<0.05). (G) The representative of MEFs clonogenic assay. (H) is the summary of G.",
    "ncbi_link": "KLF4: 16600"
  },
  {
    "caption": " (I) Disruption of KLF4 PARylation reduces KLF4 effect on Olaparib efficacy. ",
    "ncbi_link": "KLF4: 16600
KLF4: 9314"
  },
  {
    "caption": " (J-K) While elevated KLF4 inhibits PARP1 inhibitor efficacy in killing MDA-MB-231 cells, disruption of KLF4 PARylation partially rescue the KLF4-mediated resistance to Olaparib. J) The representative of MEFs clonogenic assay. (K) is the summary of J. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (L) Elevated KLF4 expression increases resistance to Olaparib in MDA-MB-468 (BRCA-proficient) cells, while disruption of KLF4 PARylation attenuates KLF4-driven resistance to Olaparib. ",
    "ncbi_link": "BRCA: 672
KLF4: 9314"
  },
  {
    "caption": " Elevation of mutant KLF4 shows the same effect as WT KLF4 to Olaparib in BRCA1 mutant cell lines HCC1937 cells. No significant difference between expression of wild-type KLF4 and KLF4 PARylation-deficient mutant was observed in HCC1937 cells. ",
    "ncbi_link": "BRCA1: 672
KLF4: 9314"
  },
  {
    "caption": " Elevation of mutant KLF4 shows the same effect as WT KLF4 to Olaparib in BRCA1 mutant cell lines MDA-MB-436 cells. No significant difference between expression of wild-type KLF4 and KLF4 PARylation-deficient mutant was observed in MDA-MB-436 cells. ",
    "ncbi_link": "BRCA1: 672
KLF4: 9314"
  },
  {
    "caption": " Modulating KLF4 by knockdown or overexpression affects cellular response of MDA-MB-231 to Olaparib in clonogenic assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Modulating KLF4 by knockdown or overexpression affects cellular response of MCF7 to Olaparib in clonogenic assay. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Modulating KLF4 by knockdown or overexpression significantly affects synergism on Olaparib/Doxorubicin in MDA-MB-231(Q) Data are mean ± SEM; one-way ANOVA was used for the statistical analysis. The asterisk in the panels represents the significant difference (p<0.05). The exact p-Values were supplied in Appendix Table S4. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " Modulating KLF4 by knockdown or overexpression significantly affects synergism on Olaparib/Cisplatin in MCF7 Data are mean ± SEM; one-way ANOVA was used for the statistical analysis. The asterisk in the panels represents the significant difference (p<0.05). The exact p-Values were supplied in Appendix Table S4. ",
    "ncbi_link": "KLF4: 9314"
  },
  {
    "caption": " (A) Depletion of KLF4 significantly enhances the efficacy of Olaparib in killing TNBC cells (4T1). 4T1 cells with stable expression of shKLF4 were implanted into mammary fat pad of BALB/c Nude mice. Drug treatment was started at 10th day. Placebo or Olaparib at the dose of 100 mg/kg was administrated daily for twelve days. Tumor volumes were measured every other day. Tumor volumes were measured every other day. n=9 per group, p values were labeled in figure, one-way ANOVA assay. ",
    "ncbi_link": "KLF4: 16600"
  },
  {
    "caption": "C, Dusp1 mRNA levels on P74. Two-tailed unpaired t test. t = 0.3691, p = 0.7307. n = 3 biological replicates per group. Data information: ASE, adolescent saline-exposed mice during adulthood; ACE, adolescent cocaine-exposed mice during adulthood The data were presented as the mean ± SEM. Statistical analyses were performed using unpaired t-tests. N.S., p > 0.05, *, p < 0.05, **, p < 0.01 versus ASE mice",
    "ncbi_link": "Dusp1: 19252"
  },
  {
    "caption": "B, Dusp1 mRNA levels on P78. Two-tailed unpaired t test. t = 4.413, p = 0.0116. n = 3 biological replicates per group. Data information: Ctrl, control virus-treated mice; OE, overexpression virus-treated mice. The data were presented as the mean ± SEM. Statistical analyses were performed using Two-way ANOVA or unpaired t-tests. N.S., p > 0.05, #, p < 0.05, versus baseline (pre-test CPP score); N.S., p > 0.05, *, p < 0.05, **, p < 0.01 versus Ctrl virus-treated mice.",
    "ncbi_link": "Dusp1: 19252"
  },
  {
    "caption": "B, Dusp1 mRNA levels on P78. Two-tailed unpaired t test. t = 9.250, p < 0.0001. n = 4 biological replicates per group. Data information: Ctrl, control virus-treated mice; KD, knocking-down virus-treated mice. The data were presented as the mean ± SEM. Statistical analyses were performed using Two-way ANOVA or unpaired t-tests. N.S., p > 0.05, ##, p < 0.01 versus baseline (pre-test CPP score); N.S., p > 0.05, *, p < 0.05, **, p < 0.01 versus Ctrl virus-treated mice.",
    "ncbi_link": "Dusp1: 19252"
  },
  {
    "caption": "(C) Cultured neurons and (D) DRG section from Avil-Cre::Ret+/eGFPmice displaying native eGFPfluorescence and stained with IB4. Different levels of eGFP intensity (high -indicated by arrows and low -indicated by arrowheads) are detected across IB4+ and IB4- cells. Scale bar, 50 μm.",
    "ncbi_link": "Cre: "
  },
  {
    "caption": "(A) Ret-eGFPHi:IB4Neg and Ret-eGFPLo:IB4Negneurons display distinct expression profiles. A volcano plot of fold change expression in Ret-eGFPLo:IB4Neg versus Ret-eGFPHi:IB4Neg against probability. Ret has higher expression in the Ret-eGFPHi:IB4Neg subset, which also shows an up regulation of the Ret co-receptor Gfra2 and Fam38b, encoding for the mechanosensitive ion channel Piezo2. The Ret-eGFPLo:IB4Neg subset, displays an array of molecules previously associated with itch (marked in red).",
    "ncbi_link": "Gfra2: 14586
Fam38b: 667742
Piezo2: 667742"
  },
  {
    "caption": "(B) Itch-associated transcripts are enriched in the Ret-eGFPLo:IB4Neg population compared to all DRGneurons. Volcano plot of fold change expression in Ret-eGFPLo:IB4Negneurons versus sorted neurons from Avil-Cre::R26tdRFPmice against probability. Molecules linked to itch perception are significantly upregulated in the Ret-eGFPLo:IB4Neg subset.",
    "ncbi_link": "Cre: 
R26: 14910
Ret: 19713"
  },
  {
    "caption": "(C) Gene expression within the Ret-eGFPLo:IB4Neg population is confirmed by triple comparison between Ret-eGFPLo:IB4Neg, Ret-eGFPHi:IB4Neg and Avil-Cre::R26tdRFPdatasets.",
    "ncbi_link": "Cre: 
R26: 14910"
  },
  {
    "caption": "(A−H) SstCre mediated recombination of the Ret locus drives eGFP expression in sensory neurons that do not bind to IB4 or co-express NF200 or TH. Triple immunostaining of DRG from Sst-Cre::ReteGFP/+mice with RetGFP (A), IB4 (B) and NF200 (C), and RetGFP (E), IB4 (F) and TH (G).",
    "ncbi_link": "Cre: 
Ret: 19713
Sst: 20604"
  },
  {
    "caption": "(I) Quantification of SstCre::Ret-eGFP expression in DRG. (J) Quantification of co-expression of SstCre::Ret-eGFP with neuronal markers (n=8827 cells from 3 mice).",
    "ncbi_link": "Sst: 20604"
  },
  {
    "caption": "(K−M) Peripheral projections of sensory neurons from Sst-Cre::Rosa26SnapCaaXmice terminate in the hairy skin as free nerve endings. Non-innervated hair follicles are indicated by arrows. Double labelling using TMRStar to label SNAP-tag (K) and DAPI (L). Scale bars, 50 μm.",
    "ncbi_link": "Cre: 
Rosa26: 14910
Sst: 20604"
  },
  {
    "caption": "(A-B) Contour diagram of dissociated sensory neurons from Sst-Cre::ReteGFP/+ (A) and Avil-Cre::ReteGFP/+neurons (B), plotted according to their native eGFP expression and IB4 binding. Only one subset of Ret-eGFP cells can be defined within the Sst-Cre::ReteGFP/+ dissociated DRGneurons. This displays the same range of eGFPfluorescence as the Ret-eGFPLo:IB4Neg population and doesn't bind to IB4.",
    "ncbi_link": "Cre: 
Sst: 20604"
  },
  {
    "caption": "(C) Quantitative RT-PCR analysis of selected transcripts in the Sst-Cre::ReteGFP (darker colors) and Ret-eGFPHi:IB4Neg (lighter colors) subsets displayed as differential expression compared to the Ret-eGFPHi:IB4Neg subset. Almost all the genes that are up-regulated in the Ret-eGFPLo:IB4Neg compared to the Ret-eGFPHi:IB4Neg subset are also enriched in the Sst-Cre::ReteGFP population (n=3)",
    "ncbi_link": "Cre: 
Sst: 20604"
  },
  {
    "caption": "(A-G) Ablation of Sst-Cre::AviliDTR positive sensory neurons by injection of diphtheria toxin (DTX). Immunostaining of DRG from Sst-Cre::AviliDTRmice with an antibody against the diphtheria toxin receptor and IB4 in the absence of diphtheria toxin (A-C) and after systemic injection of diphtheria toxin (D-F).",
    "ncbi_link": "Sst: 20604"
  },
  {
    "caption": "(A-B) Nociceptive withdrawal thresholds in control (AviliDTR without the Cre) and Sst-Cre::AviliDTRmice after systemic diphtheria toxin injection. No significant differences in thermal (A) or mechanical (B) withdrawal reflexes after ablation of SstCre positive neurons.",
    "ncbi_link": "Sst: 20604"
  },
  {
    "caption": "(C-F) Scratching behavior after a single intradermal injection of the indicated pruritogen observed for 1 hour. All compounds evoked a significant increase in the number of scratching bouts compared to vehicle alone in control (AviliDTR) or Sst-Cre::AviliDTRmice. Diphtheria toxin injection in control mice (AviliDTR) had no effect on scratching behavior evoked by histamine (C), chloroquine (D), IL-31 (E) or 5HT1F agonist Ly344864 (F) but significantly reduced responses to IL31, or Ly344864 in Sst-Cre::AviliDTRmice. n-numbers indicated in brackets, asterisk denotes p<0.05, two way RM ANOVA, Holm-Sidak multiple comparison. Error bars indicate SEM.",
    "ncbi_link": "Sst: 20604"
  },
  {
    "caption": "qRT-PCR gene expression analysis showing the fold change of Pi3K/mTOR associated gene panel in KSL cells sorted from: (A) Molm-14-xenografted mice",
    "ncbi_link": "mTOR: 56717
Pi3K: 18706"
  },
  {
    "caption": "qRT-PCR gene expression analysis showing the fold change of Pi3K/mTOR associated gene panel in KSL cells sorted from: IF injected mice with Molm-14-EV relative to their controls and normalized to Gapdh endogenous control.",
    "ncbi_link": "Gapdh: 
mTOR: 56717
Pi3K: 18706"
  },
  {
    "caption": "Dual Luciferase reporter assay. NIH-3T3 was transfected with the miRNA mimics. Three hours later the cells were transfected with the Raptor 3′UTR cloned into the psiCheck-2 vector for a total of 48 hours. Data are presented as %RLU (relative luciferase units) of the miR-scramble control as means ± SEM from at least three independent experiments, performed in technical replicates.",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "Cell-cycle flow cytometric analysis using Ki67/Hoechst-33342 staining of the percentage of LT-HSC in the G0 phase after nucleofection of cKit+ cells using the AmaxaTM P3 Primary Cell 4D-Nucleoeftcor kit, (J) Cells were nucleofected with miR-Scramble (CTRL) or miR-1246 mimic (n=3) for 72 hours,",
    "ncbi_link": "miR-1246: "
  },
  {
    "caption": "Cell-cycle flow cytometric analysis using Ki67/Hoechst-33342 staining of the percentage of LT-HSC in the G0 phase after nucleofection of cKit+ cells using the AmaxaTM P3 Primary Cell 4D-Nucleoeftcor kit, Cells were nucleofected with Anti-miR-Scramble (CTRL) or Anti-miR-1246 (n=5) and 1-hour later co-treatment with Molm-14 EVs for 72 hours.",
    "ncbi_link": "miR-1246: "
  },
  {
    "caption": "Evaluation of the in vivo long-term repopulation capacity. For secondary transplantation (n=6 per group), PB samples were collected twice weekly for 12 weeks (WK) and the donor chimerism was measured by qPCR of Sex-determining Region Y (SRY) normalized to Gapdh gatekeeper as shown in the left panel. Sixteen weeks later, mice were sacrificed and BM male chimerism percentage was assessed as shown in the right panel. Tertiary transplantation, unfractionated BM cells from the secondary recipients (n=6 per group, 106 cells per mouse) were injected into tertiary 150cGy sub-lethally irradiated female recipients and blood SRY levels were assessed for 20 weeks.",
    "ncbi_link": "Gapdh: 
SRY: 6736
Sex-determining Region Y: 6736"
  },
  {
    "caption": "qRT-PCR gene expression analysis showing the fold-change of select DNA-damage response-genes panel in Molm-14-xenograft-derived: (E) Primary recipient KSL, n=6 Data indicated by bars of fold-change calculated relative to matching controls, normalized to the endogenous control Gapdh and presented as means ± SEM.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "qRT-PCR gene expression analysis showing the fold-change of select DNA-damage response-genes panel in Molm-14-xenograft-derived: Cells from W1 plating, n=4, Data indicated by bars of fold-change calculated relative to matching controls, normalized to the endogenous control Gapdh and presented as means ± SEM.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "qRT-PCR gene expression analysis showing the fold-change of select DNA-damage response-genes panel in Molm-14-xenograft-derived: Cells from W2 plating n=4. Data indicated by bars of fold-change calculated relative to matching controls, normalized to the endogenous control Gapdh and presented as means ± SEM.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "qRT-PCR analysis of the DNA-damage-genes panel in Molm-14-xenograft-derived: (M) KSL, and (N) LT-HSC, relative to matched controls. Data depicted as fold-change relative to matching controls, normalized to the endogenous control Gapdh and presented as mean ± SEM.",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "(C) Immunohistochemistry for C. burnetii in the lung on d7 after i.t. infection. Representative images and quantitation of lung tissue positive for C. burnetii (n=12-13 mice, pooled from three experiments, each normalized to the mean of WT or Acod1+/- infected mice). Each dot represents one mouse.",
    "ncbi_link": "Acod1: 16365"
  },
  {
    "caption": "representative images of liver sections and quantification of immunohistochemistry for C. burnetii in liver sections (G). n=6-11 mice (for NMII infections), pooled from two experiments. Each dot represents one mouse. (Mann-Whitney test comparing treatment and control group of NMII infected Acod1-/- mice in specified organs, *",
    "ncbi_link": "Acod1: 16365"
  },
  {
    "caption": "D. qRT-PCR  analysis of PCIF1  mRNA in the indicated cell lines. Levels were normalized to GAPDH  expression. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "GAPDH: 2597
PCIF1: 63935"
  },
  {
    "caption": "A. Western blot analysis of PCIF1  in HT29  and HCT116 cells depleted of PCIF1  using four different sgRNAs. GAPDH  served as a loading control.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "Matrigel invasion  assay  (B), of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "fibronectin adhesion  assay (C), of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "colony formation assay (D) of the indicated control and PCIF1-depleted CRC cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "wound healing migration assay  (E) of the indicated control and PCIF1-depleted CRC  cell lines. Representative images and quantification of cells are shown at the left and right, respectively, of each panel. Data are the mean ± SD of n=3 replicates/condition. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "A. LC-MS/MS  identification and quantification of m6Am  or m6A  levels in mRNA from control and PCIF1-depleted HCT116  cells. Data are presented as the enrichment of methylated  vs unmethylated mRNA. Data are the mean ± SD of n=3 biological replicates. **P < 0.01 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "B. Metagene plots analysis of   m6Am enrichment around the transcription start site (TSS) of all expressed genes in control and PCIF1-depleted HCT116  cells.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "E. Western blot  analysis of FOS  and PCIF1  in control and PCIF1-depleted HCT116  and HT29  cells. GAPDH  served as a loading control.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "F. Genome browser views of FOS   with m6Am  sites. Read coverage of input sample and IP  sample are shown in blue and red, respectively, and green rectangle indicates the m6Am  peaks located near the TSS.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "G.  m6Am-exo-qPCR  analysis of m6Am enrichment in FOS  mRNAs from the indicated HCT116  cells. GAPDH  served as a negative control. Data are the mean ± SD of n=3 biological replicates. **P < 0.01 by Student's t-test.",
    "ncbi_link": "FOS: 2353
GAPDH: 2597"
  },
  {
    "caption": "H. qRT-PCR analysis of FOS  mRNA stability in control and PCIF1-depleted HCT116  and HT29  cells treated with actinomycin D for the indicated times. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01 by Student's t-test.",
    "ncbi_link": "FOS: 2353
PCIF1: 63935"
  },
  {
    "caption": "A. Western blot  analysis of FOS  in control and FOS-depleted HCT116  and HT29  cells. GAPDH  served as a loading control.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "MTS cell proliferation assay (B), of control and FOS-depleted HCT116   cells. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "wound healing migration assay (C), of control and FOS-depleted HCT116  cells. Representative images and quantification of colonies are shown to the left and right, respectively. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "colony formation assay (D) of control and FOS-depleted HCT116  cells. Representative images and quantification of colonies are shown to the left and right, respectively. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "E. Growth  of control and FOS-depleted HCT116  tumors after subcutaneous injection into athymic nude mice. Tumor volume was recorded on the indicated days. Data are the mean ± SEM of n=10 mice/group. **P < 0.01 by Student's t-test.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "F. Survival  analysis of mice  bearing control and FOS-depleted HCT116  tumors. Data are the mean ± SEM of n= 5 mice/group. *P < 0.05 by Student's t-test.",
    "ncbi_link": "FOS: 2353"
  },
  {
    "caption": "B. mRNA expression of PCIF1  was quantified by qRT-PCR in the HCT116  cells transfected with gradient amount of control and PCIF1  siRNAs. Data are the mean ± SD of n=3 biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "C.  Western blot analysis of PCIF1  in HCT116  cells with control and PCIF1  siRNAs. GAPDH  served as a loading control.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "D. Cell viability assays were performed in in the HCT116  cells transfected with 100pmol control and PCIF1 siRNAs. Data are the mean ± SD of n=3 biological replicates. ***P < 0.001 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "F. Tumor growth  of HCT116  cells treated with 1mg/kg control and PCIF1 LNP-siRNAs starting on day 9 and mice  were intratumorally treated twice a week. Data are the mean ± SEM of n=5 mice/group. *P < 0.05, **P < 0.01 by Student's t-test.",
    "ncbi_link": "PCIF1: 63935"
  },
  {
    "caption": "A. Confocal images show Iba1-immunoreactive microglia and macrophages in RPE/choroid whole mount preparations 48 hours after laser coagulation and intravitreal application of low (0.2 µg) and high (3 µg) dose polySia avDP20 or PBS-vehicle. Laser spots of vehicle-injected SIGLEC11 transgenic (tg) and wild type control animals revealed strong accumulation of activated microglia and macrophages, which was effectively decreased in polySia avDP20-injected SIGLEC11 tg animals and to a lower extent in wild type controls. Representative images out of at least three independent experiments are shown. Scale bar: 50µm.B. Quantification of the average pixel intensity of Iba1-positive area in laser spots reflects accumulation of reactive microglia/macrophages on RPE/choroid whole mounts. In comparison to the accumulation of reactive microglia/macrophages in control animals, there is a reduced pixel intensity found in polySia avDP20-treated SIGLEC11 tg animals. Notably, treatment with a high polySia avDP20 dose (3 µg) also reduced accumulation of microglia/macrophages in laser spots of wild type animals. Data show mean +/- SD. * p< 0.05, ** p< 0.01, *** p< 0.001, One-way ANOVA followed by Fisher's LSD. WT PBS (n = 24 spots), WT 0.2 µg Sia (n = 37 spots), WT 3 µg Sia (n = 20 spots), SIGLEC11 tg PBS (n = 25 spots), SIGLEC11 tg 0.2 µg Sia (n = 35 spots), SIGLEC11 tg 3 µg Sia (n = 31 spots), WT PBS vs WT 3 µg Sia p = 0.0147, WT 0.2 µg Sia vs SIGLEC11 tg 0.2 µg Sia p = 0.0046, SIGLEC11 tg PBS vs SIGLEC11 tg 0.2 µg Sia p = 0.0071, SIGLEC11 tg PBS vs SIGLEC11 tg 3 µg Sia p < 0.0001.",
    "ncbi_link": "SIGLEC11: "
  },
  {
    "caption": "C. Confocal images of retinal whole mounts show Iba1-immunoreactive microglial cells. Retinal microglia of polySia avDP20-treated SIGLEC11 tg mice had a more ramified microglial morphology in the laser spot compared to PBS-vehicle treated mice. Interestingly, high polySia avDP20 dose (3 µg) also exerted a weak therapeutic effect in wild type animals. Representative images out of at least three independent experiments are shown. Scale bar: 20 µm.D. Percentage of retina showing activated microglial cells within the laser spots was quantified. PolySia avDP20 reduced the percentage of laser spots with activated microglia in SIGLEC11 tg animals and at high dose (3 µg) also in wild type controls. Data show mean +/- SEM. * p< 0.05, ** p< 0.01, ***p<0.001, One-way ANOVA followed by Fisher's LSD. WT PBS (n = 6 retinas), WT 0.2 µg Sia (n = 8 retinas), WT 3 µg Sia (n = 6 retinas), SIGLEC11 tg PBS (n = 8 retinas), SIGLEC11 tg 0.2 µg Sia (n = 7 retinas), SIGLEC11 tg 3 µg Sia (n = 6 retinas),WT PBS vs WT 3 µg Sia p = 0.0052, WT 0.2 µg Sia vs SIGLEC11 tg 0.2 µg Sia p = 0.0005, SIGLEC11 tg PBS vs SIGLEC11 tg 0.2 µg Sia p = 0.0159, SIGLEC11 tg PBS vs SIGLEC11 tg 3 µg Sia p = 0.001.",
    "ncbi_link": "SIGLEC11: "
  },
  {
    "caption": "A. Fundus fluorescein angiography was performed 48 hours after laser coagulation and intravitreal application of low (0.2 µg) and high (3 µg) dose polySia avDP20 or PBS-vehicle. Late stage (10-11 minutes after fluorescein injection) fundus fluorescein angiography revealed that PBS-treated wild type controls and humanized SIGLEC11 mice showed normal levels of vessel leakage whereas polySia avDP20-treated SIGLEC11 transgenic (tg) mice had lower levels of vessel leakage compared to PBS-injected wild type or SIGLEC11 tg mice. High polySia avDP20 dose reduced vascular leakage also in wild type animals. Representative images out of at least eight independent experiments are shown.B. Fundus fluorescein angiography pictures were exported from Heidelberg Eye Explorer Software and fluorescein leakage was quantified with ImageJ software (NIH). Pixel intensities of 6 regions of interest per picture were quantified and background fluorescence was subtracted. PolySia avDP20-treated SIGLEC11 tg animals showed reduced vascular leakage compared to PBS-injected wild type control and SIGLEC11 tg mice. A reduction in vascular leakage was also observed in high dose polySia avDP20-injected wild type control mice. Data show mean +/- SD. * p< 0.05, *** p< 0.001, One-way ANOVA followed by Fisher's LSD. WT PBS (n = 20 eyes), WT 0.2 µg Sia (n = 17 eyes), WT 3 µg Sia (n = 9 eyes), SIGLEC11 tg PBS (n = 16 eyes), SIGLEC11 tg 0.2 µg Sia (n = 20 eyes), SIGLEC11 tg 3 µg Sia (n = 15 eyes), WT PBS vs WT 3 µg Sia p = 0.0193, WT 0.2 µg Sia vs SIGLEC11 tg 0.2 µg Sia p < 0.0001, SIGLEC11 tg PBS vs SIGLEC11 tg 0.2 µg Sia p < 0.0001, SIGLEC11 tg PBS vs SIGLEC11 tg 3 µg Sia p = 0.0002.",
    "ncbi_link": "SIGLEC11: "
  },
  {
    "caption": "C. Anti-C5b-9 immunostaining of RPE/choroid whole mount preparations 48 hours after laser damage showed strong MAC deposition in the laser lesions of vehicle-injected controls. PolySia avDP20 treatment reduced MAC formation in a dose-dependent fashion independent of SIGLEC11 presence. Scale bar: 100 µm.D. Quantification of C5b-9 fluorescence signal intensity in the laser lesions. In comparison to the high amount of MAC deposition in vehicle-injected controls, the pixel intensity is reduced in polySia avDP20-treated eyes in a dose-dependent fashion and regardless of SIGLEC11 presence. Data show mean +/- SD. *** p< 0.001, One-way ANOVA followed by Fisher's LSD. WT PBS (n = 12 laser spots), WT 0.2 µg Sia (n = 12 laser spots), WT 3 µg Sia (n = 7 laser spots), SIGLEC11 tg PBS (n = 6 laser spots), SIGLEC11 tg 0.2 µg Sia (n = 10 laser spots), SIGLEC11 tg 3 µg Sia (n = 12 laser spots); all statistical comparisons p < 0.0001 except SIGLEC11 tg PBS versus SIGLEC11 tg 0.2 µg Sia p = 0.0004.",
    "ncbi_link": "SIGLEC11: "
  },
  {
    "caption": "A. Analysis of relative TNFSF2 gene transcription in human control and SIGLEC11/16 knockout THP1-macrophages. The levels of gene transcripts were reduced after 24 hours of co-treatment with LPS (1 µg/ml) and concentrations of 0.15 µM and 1.5 µM of polySia avDP20 in the human wild type macrophages. No response to polySia avDP20 was detectable in the knockout line. Data show mean +/- SEM. ** p < 0.01, ANOVA followed by Bonferroni. Statistical analysis was done in relation to the LPS control. WT: no treatment n=7 and p< 0.0001, PolySia avDP20 1.5 µM n=4 and p=0.0002, LPS n=7, LPS/PolySia avDP20 0.15µM n=3 and p=0.009, LPS/PolySia avDP20 1.5µM n=5 and p=0.002. Siglec11/16 KO: no treatment n=5 and p=0.01, PolySia avDP20 n=4 and p=0.122, LPS n=7, LPS/PolySia avDP20 0.15µM n=3 and p=1.0, LPS/PolySia avDP20 1.5µM n=4 and p=1.0.",
    "ncbi_link": "SIGLEC11: 114132
TNFSF2: 7124"
  },
  {
    "caption": "B. Analysis of relative TNFSF2 protein release in human control and SIGLEC11/16 knockout THP1-macrophages. The released protein levels were reduced after 24 hours of co-treatment with LPS (1 µg/ml) and concentrations of 0.15 µM and 1.5 µM of polySia avDP20 in the human wild type macrophages. No response to polySia avDP20 was detectable in the knockout line. Data show mean +/- SEM. ** p < 0.01, *** p < 0.001, ANOVA followed by Bonferroni. Statistical analysis was done in relation to the LPS control. WT: no treatment n=8 and p<0.0001, PolySia avDP20 1.5 µM n=5 and p<0.001, LPS n=7, LPS/PolySia avDP20 0.15µM n=5 and p=0.002, LPS/PolySia avDP20 1.5µM n=4 and p=0.0003. Siglec11/16 KO: no treatment n=6 and p<0.001, PolySia avDP20 1.5 µM n=5 and p<0.001, LPS n=7, LPS/PolySia avDP20 0.15µM n=5 and p=1.0, LPS/PolySia avDP20 1.5µM n=5 and p=1.0.",
    "ncbi_link": "SIGLEC11: 114132"
  },
  {
    "caption": "C. Analysis of relative VEGFA gene transcription in human control and SIGLEC11/16 knockout THP1-macrophages. Gene transcripts were reduced after 24 hours of co-treatment with LPS (1 µg/ml) and polySia avDP20 (0.15 µM and 1.5 µM) in the human wild type macrophages. No response to polySia avDP20 was detectable in the knockout macrophages. Data show mean +/- SEM. *** p < 0.001, ANOVA followed by Bonferroni. Statistical analysis was done in relation to the LPS control. WT: no treatment n=6 and p<0.0001, PolySia avDP20 1.5 µM n=5 and p<0.0001, LPS n=5, LPS/PolySia avDP20 0.15µM n=5 and p=0.0002, LPS/PolySia avDP20 1.5µM n=5 and p<0.0001. Siglec11/16 KO: no treatment n=5 and p=0.022, PolySia avDP20 n=3 and p=0.063, LPS n=4, LPS/PolySia avDP20 0.15µM n=3 and p=1.0, LPS/PolySia avDP20 1.5µM n=4 and p=1.0.",
    "ncbi_link": "SIGLEC11: 114132
VEGFA: 7422"
  },
  {
    "caption": "D. Analysis of relative VEGFA protein release in human control and SIGLEC11/16 knockout THP1-macrophages. Released protein levels were reduced after 24 hours of co-treatment with LPS (1 µg/ml) and polySia avDP20 (0.15 µM and 1.5 µM) in the human macrophages. Data show mean +/- SEM. * p < 0.05, *** p < 0.001, ANOVA followed by Bonferroni. Statistical analysis was done in relation to the LPS control. WT: no treatment n=9 and p<0.0001, PolySia avDP20 1.5 µM n=6 and p=0.009, LPS n=9, LPS/PolySia avDP20 0.15µM n=6 and p=0.043, LPS/PolySia avDP20 1.5µM n=7 and p=0.0001. Siglec11/16 KO: no treatment n=9 and p=0.349, PolySia avDP20 1.5 µM n= 6 and p=0.249, LPS n=7, LPS/PolySia avDP20 0.15µM n=6 and p=1.0, LPS/PolySia avDP20 1.5µM n=7 and p=1.0.",
    "ncbi_link": "SIGLEC11: 114132"
  },
  {
    "caption": "E. Quantification of human control and SIGLEC11/16 knockout THP1-macrophages having ingested cellular debris. PolySia avDP20 (1.5 µM) reduced the percentage of phagocytic cells having ingested drusen-like debris. No response to polySia avDP20 was detectable in the knockout macrophages. Data are presented as mean +/- SEM. n=6. *p ≤ 0.05, *** p ≤ 0.001, ANOVA followed by Bonferroni. Debris treated WT macrophages vs debris plus polySia avDP20 treated WT macrophages p = 0.028, debris plus polySia avDP20 treated WT macrophages vs KO macrophages p = 0.00012.",
    "ncbi_link": "SIGLEC11: 114132"
  },
  {
    "caption": "F. Prevention of superoxide release in activated human control and SIGLEC11/16 knockout THP1-macrophages by polySia avDP20. Cultured human THP1-macrophages were stimulated with RPE cell debris or co-stimulated with debris and polySia avDP20. Addition of debris stimulated the production of superoxide. 1.5 µM polySia avDP20 completely prevented the release of superoxide induced by debris challenge. No response to polySia avDP20 was detectable in the knockout macrophages. Data are presented as mean +/- SEM. n=6. p* ≤ 0.05, *** p ≤ 0.001, ANOVA followed by Bonferroni. Untreated WT macrophages vs debris treated WT macrophages p = 0.037, debris treated WT macrophage vs debris plus polySia avDP20 1.5 µM treated WT macrophages p < 0.001, debris plus polySia avDP20 WT macrophages vs KO macrophages p = 0.001,",
    "ncbi_link": "SIGLEC11: 114132"
  },
  {
    "caption": "Transgenic ESZscan4_Emerald cells were sorted and total RNAs were extracted and subjected to RT-qPCR. The graph shows the mRNA expression level of Arg2 in ES subpopulations.",
    "ncbi_link": "Emerald: 
Arg2: 11847
Zscan4: 665913///100043042///545912"
  },
  {
    "caption": "(B)Transgenic ESZscan4_Emerald cells were sorted and total proteins were extracted and subjected to immunoblotting. The image is a representative of three independent biological western blotting analysis on arg2 expression in sorted ESZscan4_Emerald and control cells.",
    "ncbi_link": "Emerald: 
Zscan4: 665913///100043042///545912"
  },
  {
    "caption": "Transcript (left panel) and protein expression (right panel) levels of Arg2 in ESZscan4_LNGFR cells after transfection with a non-silencing siRNA (siCtrl) or siRNA against Arg2 (siArg2).",
    "ncbi_link": "LNGFR: 
Arg2: 11847
Zscan4: 665913///100043042///545912"
  },
  {
    "caption": "Imaging flow cytometry analysis on Zscan4+ siArg2 and Zscan4+ siCtrl cells. Samples were stained by labelling histone H3 protein. The intensity of H3 fluorescent signal was measured in the nuclear region by creating a mask defined by DAPI staining. The texture feature of fluorescent signal was analysed by using the modulation method (for details see Materials and Methods). Two cell populations (R1 and R2) correspond to two different patterns of fluorescent signal: homogenous and clustered distribution, respectively.",
    "ncbi_link": "Arg2: 11847
Zscan4: 665913///100043042///545912"
  },
  {
    "caption": "Electron microscopy images of sorted ESZscan4_Emerald and control cells. Scale bar 1μm",
    "ncbi_link": "Emerald: 
Zscan4: 665913///100043042///545912"
  },
  {
    "caption": "(B) HEK293T  cells transiently expressing FLAG  and FLAG-tagged TEX264  were subjected to immunoprecipitation  (IP). Inputs (20% of the lysates) and immunoprecipitates  (from 80% of the lysates) were analyzed by immunoblotting  using the indicated antibodies.",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": "(C) HEK293T  cells transiently expressing WT or mutated TEX264-FLAG  were subjected to immunoprecipitation  with an anti-FLAG  antibody and detected with the indicated antibodies.",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": "(D and E) MEFs  stably expressing TEX264-GFP  or its mutant were cultured in starvation  media and immunostained  with an anti-LC3  antibody. Bars: 10 µm and 1 µm (insets) (D). Quantification of the number of TEX264  puncta per cell. Solid bars indicate the medians, boxes the interquartile range (25th to 75th percentile), and whiskers the 0th to 100th percentile. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test. Data were collected from 48 cells for each cell type (E).",
    "ncbi_link": "GFP: 
TEX264: 51368"
  },
  {
    "caption": "(F and G) WT and TEX264-KO HeLa  cells (with or without the indicated TEX264  mutants with a C-terminal FLAG  tag) stably expressing the ER-phagy reporter (ss-RFP-GFP-KDEL) were cultured in the presence of doxycycline  for 24 h to induce the reporter. After doxycycline  was removed, cells were cultured in  starvation  medium  lacking amino acids and serum   for 9 h (F). The band intensities of RFP  and RFP-GFP  were quantified and the ratio of RFP:RFP-GFP  (normalized to WT) is shown. Data represent the mean ± standard error of the mean (SEM) of three independent experiments. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test (G).",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": "(A and B) MEFs stably expressing TEX264-GFP  were cultured in  starvation  media  with or without  bafilomycin A1 (Baf A1) and immunostained  with anti-pTEX264 and anti-LC3  antibodies. Bars: 10 µm and 1 µm (insets) (A). Quantification of the number of pTEX264  puncta per cell. Solid bars indicate the medians, boxes the interquartile range (25th to 75th percentile), and whiskers the 0th to 100th percentile. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test. Data were collected from 35 cells for each cell type (B).",
    "ncbi_link": "GFP: 
TEX264: 51368"
  },
  {
    "caption": "(D, E and F) WT, ATG3-KO, and FIP200-KO HeLa  cells were cultured in  starvation  media  lacking  amino acids and serum  with or without Baf A1  for 1 or 5 h. Cell lysates were analyzed by immunoblotting using the indicated antibodies (D). Relative changes of the ratio of band intensities of phosphorylated TEX264  to HSP90  and total TEX264  during starvation   are shown (E and F). Data represent the mean ± SEM of three independent experiments.",
    "ncbi_link": "ATG3: 64422
FIP200: 9821"
  },
  {
    "caption": "(C) HEK293T  cells transiently expressing TEX264-FLAG  and one of the three Halo-CK2A isoforms or Halo-CK2B  were subjected to immunoprecipitation  with an anti-FLAG  antibody and detected with anti-Halo  and anti-FLAG  antibodies.",
    "ncbi_link": "FLAG: 
Halo: 
CK2A: 283106///1459///1457
CK2B: 1460
TEX264: 51368"
  },
  {
    "caption": "(D and E) HEK293T  cells transiently expressing WT or TEX264-FLAG  mutants were subjected to immunoprecipitation  (IP). Inputs (20% of the lysates) and immunoprecipitates  (from 80% of the lysates) were analyzed by immunoblotting  using the indicated antibodies (D). The band intensities in the IP  fractions were quantified, and the phospho-serine:FLAG  ratio was calculated. Data represent the mean ± SEM of five independent experiments. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test (E).",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": "(B) HEK293T cells transiently expressing WT or mutated TEX264-FLAG  were subjected to immunoprecipitation  with an anti-FLAG  antibody and detected with the indicated antibodies.",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": "(C and D) MEFs  stably expressing TEX264-GFP  or its mutants were cultured in starvation  media and immunostained  with an anti-LC3  antibody. Bars: 10 µm and 5 µm (insets) (C). The intensity of the GFP  signal under starvation  conditions was quantified at TEX264-GFP puncta and the ER. The puncta:ER signal ratio was calculated. Solid bars indicate the medians, boxes the interquartile range (25th to 75th percentile), and whiskers the 0th to 100th percentile. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test. Data were collected from 70 puncta for each cell type (D).",
    "ncbi_link": "GFP: 
TEX264: 51368"
  },
  {
    "caption": "(E and F) WT and TEX264-KO (expressing WT or TEX264-FLAG  mutants) HeLa  cells stably expressing the ER-phagy reporter were cultured in the presence of doxycycline  for 24 h to induce the reporter. After doxycycline  was removed, the cells were cultured in starvation  medium lacking amino acids and serum  for 9 h (E). The band intensities of RFP and RFP-GFP  were quantified and the ratio of RFP:RFP-GFP  (normalized to WT) is shown. Data represent the mean ± SEM of four independent experiments. Differences were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test (F).",
    "ncbi_link": "FLAG: 
TEX264: 51368"
  },
  {
    "caption": " C RNAlow neoblast size in intact animals and at 48 hpa in control or TOR KD animals (n ≥ 55). ",
    "ncbi_link": "TOR: "
  },
  {
    "caption": " D Quantification of H3P immunostaining in intact animals and at 48 hpa in control or TOR KD animals (n = 5-10). ",
    "ncbi_link": "TOR: "
  },
  {
    "caption": " E RNAlow neoblast size in intact animals and at 48 hpa in control, raptor or rictor KD animals (n ≥ 54). ",
    "ncbi_link": "raptor: 
rictor: "
  },
  {
    "caption": " F FACS plots of Hoechst and Pyronin Y stained cells isolated from intact and regenerating animals following 1 day of nocodazole treatment in control or TOR KD animals. Percentages indicate the proportion of events within each gate. ",
    "ncbi_link": "TOR: "
  },
  {
    "caption": "A Representative WISH images for Lrig-1.",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " B RNAlow neoblast size in intact animals following control or Lrig-1 knockdown (n ≥ 53 technical replicates). ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " C Quantification of H3P immunostaining in intact animals following control or Lrig-1 knockdown (n = 9-10 technical replicates). ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " D Quantification of H3P immunostaining at homeostasis (fixed at 7 days post-RNAi, white region) and at 48 hpa (amputated at 5 days post-RNAi and fixed at 7 days post-RNAi, yellow region) during the first round of regeneration in control or Lrig-1 KD animals (n = 10-17). ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " E Quantification of unpigmented blastema area (as % total tissue area) in regenerating control or Lrig-1 KD animals from 2 dpa to 7 dpa during the first round of regeneration (n = 10 animals per condition per time point). The same animals were used for all timepoints. Representative images from 7 dpa are shown. Scale bars, 500 µm. ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " F Quantification of H3P immunostaining at homeostasis (fixed at 14 days post-RNAi, white region) and at 48 hpa (amputated at 12 days post-RNAi and fixed at 14 days post-RNAi, yellow region) during a second round of regeneration in control or Lrig-1 KD animals (n = 10-18). ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": " G Quantification of unpigmented blastema area (as % total tissue area) in regenerating control or Lrig-1 KD animals from 2 dpa to 7 dpa during the second round of regeneration (n = 9-10 animals per condition per time point). The same animals were used for all timepoints. Representative images from 7 dpa are shown. Scale bars, 500 µm. ",
    "ncbi_link": "Lrig-1: "
  },
  {
    "caption": "(A-D) EM images of cortical neuropil show an absence of AVs and normal neurite profile in 9-mo-old NTg mouse brains (A, arrowheads outline normal neurites) and a marked accumulation of AVs within enlarged or dystrophic neurites in PS1/APP mice (B, arrowheads outline dystrophic neurite profiles in C) and biopsied brain material from an AD patient (B, inset). At higher magnification (C), AVs include autophagosomes (arrows) and multilamellar bodies (arrowhead). In normal dendrites of PS1/APP mice, multiple AVs are frequently seen (D, arrows).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(E and F) LC3 quantification analyzed from immunoblots of LC3-I and LC3-II (top) in prefrontal cortical homogenates from cases of nonaffected (Cont), early stage (preclinical) AD (AD-ES), and moderate AD (AD-MS; E), and from brains of 18-22-mo-old PS1/APP (PA) mice (n = 3; F) compared with nontransgenic (NTg) controls (n = 3; *, P < 0.01). Error bars represent SEM.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(G-L) LC3 immunofluorescence in 9-mo-old PS1/APP mice can be seen mainly as puncta in dystrophic dendrites of the cortex (G, arrows) and along adjacent dendrites. LC3 (H, arrows) is strong in dystrophic neurites in the periphery (asterisks) of a thioflavin S-labeled plaque core (H, inset) but is less so in neurites closest (H, arrowheads) to the Aβ deposit. LC3 is diffuse and uniform in neurons of NTg mice (I and J) but is predominantly vesicular and distributed more to the dendrites (arrows) than the cell soma (arrowheads) in 9-mo-old PS1/APP cortex (K and L).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Ultrastructural inspection of brain tissue from PS1/APP mice (A-D) shows that AVs (A and B, arrows) are five times more frequent in the dendrites of 8-wk-old PS1/APP than in those of age-matched NTg mice. The frequency of AVs per EM field (C) and mean number of AVs per EM field (D) within the hippocampal molecular layer (n = 3) are shown.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "LC3immunoblot and analysis (E) and immunofluorescent labeling (F-K) of the hippocampaldendrites (brackets) in 8-9-wk-old PS1/APP and NTg mice show LC3-II elevation (P < 0.05) in 8-wk-old PS1/APP compared with NTg mice (E). (D) *, P < 0.001. (E) *, P < 0.05. Error bars represent SEM. LC3 immunoreactivity in pyramidal celldendrites is increased in 9-mo-old (F-H) and 9-wk-old (I-K) PS1/APPmice and frequently exhibits a punctate labeling pattern, which is more evident at 9 mo than at 9 wk (H and K, arrows) and is uncommon in NTg mice (F and I). Bars (F, G, I, and J), 20 μm; (H and K), 10 μm.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Immunolocalization of PS1 in plaques and AVs within dystrophic neurites in AD and PS1/APP mice. Cingulate cortex from 9-mo-old PS1/APP mice immunolabeled with PS1 antibody and NT1 showed that PS1 localized to plaques (A). At higher magnification, anti-PS1 antibodies strongly labeled neuritic profiles that were distributed within the plaque corona (B).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "PS1 immunoreactivity is identified by IEM in AVs within dystrophic neurites of PS1/APP animals (C and D)Arrowheads identify tubulovesicular membrane labeling. PS1 (C-F, arrows) was localized on the outer limiting membrane of the AV but not in mitochondria (Mito) or on plasma membranes (PM).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Induction of macroautophagy in L/APP, SH-SY5Y, and N2a cells. (A and B) EM images showing changes in the number of AVs (arrows) in L/APP-overexpressing APP695 (L/APP cells) grown in complete medium (A, top left) or in medium lacking Leu and His (A, top right) for 6 h and in SH-SY5Y cells grown in the presence (A, bottom left) or absence (A, bottom right) of serum. At higher magnification, early and late AVs with typical morphologies are seen in a Leu/His-deprived L/APP cell (B).",
    "ncbi_link": "APP: 249"
  },
  {
    "caption": "(D) Western blots confirm the cytochemical evidence for increased LC3-II levels as well as phospho-mTOR (P-2481) but not total mTOR after macroautophagy induction by Leu and His deprivation or 10 nM rapamycin (Rap) and macroautophagy inhibition by 5 mM 3MA in L/APP, N2a, and SH-SY5Y cells. Immunoblots for LC3 in SH-SY5Y cells and P-2481 mTOR in L/APP cells have been spliced but are derived from the same blot.",
    "ncbi_link": "APP: 249"
  },
  {
    "caption": "Immunolocalization of Aβ in AVs from L/APP cells and PS1/APPbrains and γ-secretase components (PS1 and nicastrin) in L/APP cells. Immunogold localization of Aβ40 (A), Aβ42 (B), PS1 (C), nicastrin (D), and in the absence of primary antibody (E) in L/APP cells grown for 6 h in the absence of Leu and His. (F) Quantification of gold particle frequency in AV or tubulovesicular compartments (TBV), which comprise 27.0 ± 11.0 and 19.2 ± 7.2%, respectively, of the total cell area. Error bars represent SEM.",
    "ncbi_link": "APP: 249"
  },
  {
    "caption": "(G and H) IEM followed by silver stain enhancement for Aβ40 was performed in 9-mo-old PS1/APP mice.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A and B) Ultrastructure of AVs (A1 and A2) and lysosomes in subcellular fractions from serum-deprived L/APP cells (A) and Western blot analysis (B) for LC3-II, rab24, APP, βCTF, PS1 (PS1 amino-terminal fragment), and nicastrin (NCT) in L/APP subcellular fractions. AVs, A1 and A2; L, lysosomes; E, tubulovesicular compartments (Golgi/ER/endosomes); P, postnuclear pellet; C, cytosol; M, mitochondria. Empty lanes in the original blot have been removed from the figure and noted with a white line.",
    "ncbi_link": "APP: 249"
  },
  {
    "caption": "(G) γ-Secretase activity in AV and lysosome fractions from mice blastocysts in which the PS1 and PS2 genes were deleted (PS KO; BD8) or in which human PS1 was stably transfected into the PS KO blastocysts (hPS1; BD8/hPS1). Numbers on x axis are in minutes.",
    "ncbi_link": "hPS1: 5663
PS1: 19164
PS2: 19165"
  },
  {
    "caption": "C) Immunofluorescence image of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP targeted cells stained with antibodies against CENP-T. Images in C maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "E) Quantification of CENP-T signal intensity at MUC4 ectopic foci vs. endogenous centromeres, normalised to CENP-T signal intensity at endogenous centromeres (=1, red line). LinesLines = Mean ± SD, 3 experiments, each with ≥ 10 metaphases analysed per condition. Each point = 1 focus or centromere. ns = p>0.05, *** = p<0.01, **** = p<0.001 (Kruskal Wallis test with Dunn's multiple comparison correction).",
    "ncbi_link": "MUC4: 4585"
  },
  {
    "caption": "H) Quantification of KNL‑1 signal intensity at MUC4 foci, normalised to KNL‑1 signal intensity at centromeres (=1, red line). LinesLines = Mean ± SD, 3 experiments, each with ≥ 10 metaphases analysed per condition. Each point = 1 focus or centromere. ns = p>0.05, *** = p<0.01, **** = p<0.001 (Kruskal Wallis test with Dunn's multiple comparison correction).",
    "ncbi_link": "MUC4: 4585"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. C) Immunofluorescence images of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP targeted cells stained with antibodies against CENP-T. Images in are maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. F) Immunofluorescence images of CENP‑T∆C‑dCas9‑EGFP targeted cells stained with antibodies against KNL-1. Images in ,F are maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. I) Immunofluorescence images of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP targeted cells stained with antibodies against Ndc80. Images in I) are maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. A) Immunofluorescence images of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP targeted metaphase cells stained with antibodies against alpha-tubulin. B) Immunofluorescence images of mitotic cells ­­­with CENP‑T∆C‑dCas9‑EGFP targeting after nocodazole treatment. C) Length measurements of individual EGFP foci in µm. Example measurements are indicated on zooms in A-B) in orange. Data is ≥20 cells per condition, from 1 experiment. Lines = Mean ± SEM. * = p<0.05, ** = p<0.01,**** = p<0.001 (Kruskal-Wallis with multiple comparison correction). Images in A,B are maximum intensity projections taken across the depth of the EGFP foci. In A,B) Orange bars = measured lengths in C.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. D) Immunofluorescence images of metaphase cells with CENP-T∆C-dCas9‑EGFP targeting after cold treatment, stained with antibodies against alpha-tubulin. E) Percentage of metaphase cells showing microtubule (MT) recruitment. ≥50 metaphases per condition, from 1 experiment.. are maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP-T: 80152
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN in HEK293T cells. F) Frames from live cell imaging of cells with dCas9 targeted to Chr9-CEN, or an EGFP negative cell. are maximum intensity projections taken across the depth of the EGFP foci.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. A) Immunofluorescence images of paired EGFP foci for each attachment status category. Images were chosen where both the EGFP foci and any of their attachments lay in the same Z-plane for clarity of presentation. B) Percentage of paired EGFP foci showing each attachment status. are from ≥75 EGFP foci pairs from n≥15 metaphases per condition 1 experiment for",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Targeting of dCas9-EGFP or CENP‑T∆C‑dCas9‑EGFP to Chr9-CEN and Chr1‑TELO in HEK293T cells. C) Immunofluorescence images of CENP‑T∆C‑dCas9‑EGFP targeted metaphase cells stained with antibodies against Mad2. D) Percentage of individual EGFP foci showing EGFP and Mad2 signal co-localisation, in metaphase cells with CENP‑T∆C-dCas9-targeting. 2 experiments for (D). Image in C) is a maximum intensity projection taken across the depth of the EGFP signal. Scale bars = 1µm on small images and zooms, 5µm on larger images in C).",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "Immunofluorescence images from CENP‑T∆C‑dCas9‑EGFP targeted metaphase cells stained with antibodies against Mad2 and alpha-Tubulin, showing examples of microtubule attached (G) EGFP foci. H) Percentage of individual EGFP foci with EGFP and Mad2 signal co‑localisation attached (H) EGFP foci. are from ≥75 EGFP foci pairs from n≥15 metaphases per condition 1 experiment for H) are single Z-slices.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP‑T: 80152"
  },
  {
    "caption": "C,D) Example images of chromosome mis-segregation events involving the target locus (EGFP signal) in anaphase HEK293T (C) or HCT116 (D) cells with CENP-T∆C-dCas9‑EGFP targeting after Mps1i pulse. E,F) Mis‑segregation rate in fixed dCas9-targeted HEK293T (E) or HCT116 (F) cells after Mps1i pulse, involving only EGFP+ chromosomes, only EGFP- chromosomes or both. Bars = mean ± SD, 3 experiments for each cell line, each with ≥25 anaphase cells per condition. * = p<0.05, **= p<0.01, *** = p<0.001, **** = p<0.0001 (Oneway ANOVA with Šidák's multiple comparison correction, in E/F) comparing the mis-segregation rate for any events involved EGFP).",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP-T: 80152"
  },
  {
    "caption": "G-H) Frames from live cell imaging of HEK293T H2B-RFP cells after treatment with Mps1i (t=0), with CENP‑T∆C‑dCas9‑EGFP targeted to Chr9-CEN or Chr1-TELO. Frames are either across the duration of the 4 h movie (G) or show examples of the different categories of fate (H). I) Percentage of CENP-T∆C-dCas9‑EGFP targeted cells that made an EGFP+ error in anaphase, categorised by subsequent fate of EGFP signal in daughter cells 3 h after Mps1i addition. Assessed by live cell imaging. ≥22 cells with error per condition, combining data from ≥3 independent experiments.",
    "ncbi_link": "EGFP: 
Cas9: 69900935
CENP-T: 80152
CENP‑T: 80152"
  },
  {
    "caption": "(g,h) HepG2 cells stably transduced with mCherry (mCh)-GFP-LC3-expressing retroviruses were treated with Con, Rap or PA for 9 h and examined under a live confocal microscope (g). Yellow dots represent autophagosomes while red dots indicate autolysosomes in which GFP signal was faded out. Number of autolysosomes was quantified (h; n=7). Scale bar, 5 μm. All data are shown as mean±s.e.m. ***P0.001 (Student's t-test). Molecular weight markers are indicated in kDa.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A-C)  Extra-mitochondrial  puncta formation of CHCHD2T61I in MEFs. Chchd2KO cells were transfected with the CHCHD2WT-HA  and CHCHD2T61I-HA  plasmids. At the indicated times, cells were fixed and stained  with anti-HA  and anti-Tom20  antibodies, and observed by confocal microscopy. In (A), representative images are shown. Magnified images of the areas within the dashed squares are shown in the insets. Representative images at lower magnification are shown in Appendix Fig. S1D. (B, C) Quantification of cells displaying mitochondrial CHCHD2   and extra-mitochondrial CHCHD2   puncta (n ≥ 100 cells in each experiment). In (B, C, data are shown as the mean ± SD (n = 3). Comparisons were performed using unpaired two-tailed Student t-tests and one-way ANOVA followed by the Tukey post-hoc tests. **p < 0.01",
    "ncbi_link": "HA: 
Chchd2: 14004
CHCHD2: 51142"
  },
  {
    "caption": "(D, E) Extra-mitochondrial  puncta formation of CHCHD2T61I in Neuro2a  cells. Neuro2a  cells were transfected with the CHCHD2WT-HA  and CHCHD2T61I-HA  plasmids for 4 hr, then cultured with medium containing 2% FBS  and 10 µM retinoic acid for neuronal  differentiation. At 28 hr after transfection, cells were fixed and stained  with anti-HA  and anti-Tom20  antibodies. In (D), representative images are shown. Magnified images of the areas within the dashed squares are shown in the insets. Representative images at lower magnification are shown (E) Quantification of cells displaying mitochondrial CHCHD2   and  extra-mitochondrial CHCHD2   puncta (n ≥ 100 cells in each experiment). In E, data are shown as the mean ± SD (n = 3). Comparisons were performed using unpaired two-tailed Student t-tests and one-way ANOVA followed by the Tukey post-hoc tests. **p < 0.01",
    "ncbi_link": "HA: 
CHCHD2: 51142"
  },
  {
    "caption": "Neuro2a   cells were transfected with the CHCHD2WT-HA  and  CHCHD2T61I-HA  plasmids for 4 hr, and then cultured in medium containing 2% FBS  and 10 µM retinoic acid to induce neuronal  differentiation. At 28 hr after transfection, cells were fixed and stained  with an anti-HA  antibody and ProteoStat  protein aggregation dye (A, B), anti-HA  and anti-Nefl  antibodies (C, D), anti-HA and anti-p-Nefl473 antibodies (E, F), In (A, C, E, representative images are shown. Magnified images of the areas within the dashed squares are shown in the inset. Arrowheads indicate colocalized  puncta between CHCHD2T61I-HA  and aggresomes  or the indicated proteins. Representative images at lower magnification are shown (B, D, F, The amount of aggresomes (B), Nefl (D), p-Nefl473 (F) was measured as the fluorescence intensity per cell (n  = 30 cells in each experiment). Red bars indicate mean values. In (B, D, F, comparisons were performed using unpaired two-tailed Student t-tests. *p < 0.05. **p < 0.01",
    "ncbi_link": "HA: 
CHCHD2: 51142"
  },
  {
    "caption": "Neuro2a  cells were transfected with the CHCHD2WT-HA  and CHCHD2T61I-HA  plasmids for 4 hr, and then cultured in medium containing 2% FBS  and 10 µM retinoic acid to induce neuronal  differentiation. At 28 hr after transfection, cells were fixed and stained  with anti-HA  and anti-p-α-Synuclein129 (p-α-Syn129) antibodies (G, H). In G), representative images are shown. Magnified images of the areas within the dashed squares are shown in the inset. Arrowheads indicate colocalized  puncta between CHCHD2T61I-HA  and the indicated proteins. Representative images at lower magnification are shown H) The amount of p-α-Syn129 (H) was measured as the fluorescence intensity per cell (n  = 30 cells in each experiment). Red bars indicate mean values. In H, comparisons were performed using unpaired two-tailed Student t-tests. *p < 0.05. **p < 0.01",
    "ncbi_link": "HA: 
CHCHD2: 51142"
  },
  {
    "caption": "(E, F) Interaction  between CHCHD2T61I and Csnk1e/d. Neuro2a  cells were transfected with the CHCHD2WT-HA  and CHCHD2T61I-HA  plasmids together with pmax-GFP  (to detect transfected cells), and were differentiated into neuronal  cells at 4 hr after transfection. At 28 hr after transfection, cells were fixed and the PLA  was performed using anti-HA  and anti-Csnk1e/d antibodies and Duolink PLA  reagents. In (E), PLA  signals were clearly observed in cells expressing CHCHD2T61I-HA, but were faint and localized  in the cytosol  in cells expressing CHCHD2WT-HA. Representative images at lower magnification are shown In (F), the number of PLA signals were counted (n  = 50 cells in each experiment). Red bars indicate mean values. In F), comparisons were performed using the unpaired two-tailed Student t-test and one-way ANOVA followed by the Tukey post-hoc test. *p < 0.05. **p < 0.01. NS: not significant",
    "ncbi_link": "GFP: 
HA: 
CHCHD2: 51142"
  },
  {
    "caption": "(D-I) Neuro2a  cells were transfected with the CHCHD2T61I-HA  plasmid together with the indicated siRNAs, and were differentiated into neuronal  cells after 4 hr. At 28 hr after transfection, cells were fixed and stained  with anti-HA, anti-p-Nefl473, and anti-p-α-Syn129 antibodies, or ProteoStat aggresome  detection dye. Similar experiments were performed by the addition of PF-670462  (10 µM) after 4 hr of transfection instead of gene silencing. In (D, F, H), representative images are shown. Magnified images of the areas within the dashed squares are shown in the insets. Arrowheads indicate colocalized  puncta between CHCHD2T61I-HA  and the indicated phosphorylated  proteins or aggresomes. In (E, G, I), the amount of p-Nefl473 (E), p-α-Syn129 (G), and aggresomes (I) was measured as the fluorescence intensity per cell (n = 30 cells in each experiment). Red bars indicate mean values. In E, G, I), comparisons were performed using one-way ANOVA followed by the Tukey post-hoc tests or unpaired two-tailed Student t-test. *p < 0.05; **p < 0.01. NS: not significant",
    "ncbi_link": "HA: 
CHCHD2: 51142"
  },
  {
    "caption": "(F-J) The same experiments as Fig. 5G-K were performed using PF-670462-infused and vehicle-infused Chchd2T61I knock-in mice.",
    "ncbi_link": "Chchd2: 14004"
  },
  {
    "caption": "(A) Photos of the midbrain  of a control subject (left) and PD patient  harboring the CHCHD2T61I mutation (right). The dashed lines indicate the SNpc. A portion of the midbrain  of the control subject was lost when slicing.",
    "ncbi_link": "CHCHD2: 51142"
  },
  {
    "caption": "(B-G) Colocalization  of extra-mitochondrial CHCHD2T61I with  CSNK1E/D, p-NEFL472, and p-α-SYN129 in the brain  of a PD patient  harboring the CHCHD2T61I mutation. Each brain  section was deparaffinized and immunostained  with anti-CHCHD2   and anti-ANT1/2 (B), anti-CSNK1E/D (C), anti-p-NEFL472 (D, E), or anti-p-α-SYN129 antibodies (F, G). Arrowheads indicate extra-mitochondrial CHCHD2T61I puncta (B), and puncta showing colocalization  of CHCHD2T61I with CSNK1E/D (C), p-NEFL472 (D), and p-α-SYN129 (F). Arrows indicate weaker colocalization  between  CHCHD2T61I and the indicated proteins in the control brain  (C, D, F). Dashed lines indicate cell shapes. In (E, G), the amount of p-NEFL472 (E) and p-α-SYN129 (G) was measured by the average fluorescence intensity per cell (n  = 30 cells in each experiment). Red bars indicate mean values. Comparisons were performed using the unpaired two-tailed Student t-tests. **p < 0.01",
    "ncbi_link": "CHCHD2: 51142"
  },
  {
    "caption": "iPSCs  were prepared from a healthy control and a PD patient  harboring the CHCHD2T61I mutation. An isogenic control iPSC  line was generated by the correction of the gene mutation Then, these iPSC  cells were differentiated into dopaminergic (DA) neurons, and analyzed by immunofluorescence  using anti-CHCHD2 (A-E), anti-ANT1/2 (A), anti-CSNK1E/D (B), anti-p-NEFL472 (C), and anti-p-α-SYN129 antibodies (D) Arrowheads indicate extra-mitochondrial CHCHD2T61I (A), puncta showing colocalization  of CHCHD2T61I with CSNK1E/D (B), p-NEFL472 (C, , and p-α-SYN129 (D, Dashed lines indicate cell shapes.",
    "ncbi_link": "CHCHD2: 51142"
  },
  {
    "caption": "CHCHD2T61I iPSC-derived DA neurons were treated with  PF-670462 (10 µM) for 20 hr and analyzed by immunofluorescence  using anti-CHCHD2  and anti-p-α-SYN129 antibodies (G), and ProteoStat aggresome  dye (H). Arrowheads indicate puncta showing colocalization  of CHCHD2T61I with p-α-SYN129 G) or aggresomes  H). Dashed lines indicate cell shapes.",
    "ncbi_link": "CHCHD2: 51142"
  },
  {
    "caption": "(B) Western blot  analyses of whole-cell lysates of wild-type (CC-124), bld10, bld10::B10-N-HA, bld10::B10-M-HA, and bld10::B10-C-HA  cells using antibodies against the C-terminal region of Bld10p  (Anti-Bld10-C antibody, upper blot) and the HA  antigen (Anti-HA  antibody, lower blot). The apparent molecular weights of tagged Bld10ps are slightly larger than that of native  Bld10p  due to their HA  tags.",
    "ncbi_link": "bld10: 
HA: "
  },
  {
    "caption": "(C) Percentages of flagellated  cells in wild-type (CC-124), bld10, bld10::B10-N-HA, bld10::B10-M-HA, bld10::B10-C-HA, bld12, bld10bld12, bld10bld12::∆N3, bld10bld12::∆C2, bld10::∆N3, and bld10::∆C2 cells. Cells with two (red), one (green), and zero (blue) flagella  were counted. n, number of cells counted.",
    "ncbi_link": "bld10: 
bld12: 
HA: "
  },
  {
    "caption": "(A)  Western blot  analyses of whole-cell lysates of wild-type (CC-124), bld12, bld10, bld10bld12, and  bld10bld12::∆N3 cells using an antibody against the C-terminal one-third of Bld10p  (Anti-Bld10-C antibody). The band corresponding to truncated Bld10p  (Bld10p  ∆N3) overlaps with a non-specific band at 75 kDa. (B) Western blot analyses of whole-cell lysates of wild-type (CC-124), bld12, bld10, bld10bld12, and bld10bld12::∆C2 cells using an antibody raised against the N-terminal 120 amino-acid sequence of Bld10p  (Anti-Bld10-N antibody).",
    "ncbi_link": "bld10: 
bld12: "
  },
  {
    "caption": "(C) Cross-sectional electron micrographs of centrioles  in bld12, bld10::∆N3, bld10bld12::∆N3, bld10::∆C2, and bld10bld12::∆C2 cells. Scale bar, 100 nm. (D) Distribution of the number of triplets in centrioles  of bld12, bld10::∆N3, bld10bld12::∆N3, bld10::∆C2, and bld10bld12::∆C2 cells. Red lines denote the normal number of microtubules  in the centriole  (nine). n, number of centrioles  observed.",
    "ncbi_link": "bld10: 
bld12: "
  },
  {
    "caption": "(A and B) Cross-sectional electron micrographs  of the proximal  (A) and distal  (B) regions of centrioles  containing eight or nine triplets in bld12, bld10bld12::∆N3, and  bld10bld12::∆C2 cells. The arrangement of triplets in images of axonemes  were circularized using CentrioleJ program The colored circles represent the circles inscribed to the innermost positions of the A-tubules in the centriole. Scale bar, 100 nm. (C and D) Distances between adjacent  A-tubules at the proximal  (C) and distal  (D) regions of centrioles  containing seven, eight, nine, and ten triplets in wild-type (cw92), bld12, bld10bld12::∆N3, and bld10bld12::∆C2 cells. The distances between the contact points of A-tubules with the inscribed circle were measured. These distances were ~10% shorter in cells expressing truncated Bld10ps  than in wild-type and bld12  cells. ***, P<0.0001. n, number of centrioles  measured. Data information: Data were analyzed by unpaired t-test. The graphs show mean ± SEM.",
    "ncbi_link": "bld10: 
bld12: 
Bld10ps: "
  },
  {
    "caption": "(E) Lengths of A-C linkers in wild-type (cw92), bld12, bld10bld12::∆N3, and  bld10bld12::∆C2 centrioles. Centrioles  containing nine triplets and eight triplets were separately analyzed. n, number of A-Clinkers measured. (F) Angles between adjacent triplets in centrioles  analyzed in panel €. The angle (θ) measured was defined as indicated in the schematic diagram; the angle between the line connecting the centers of  B-tubules of the two adjacent triplets (black line) and the line connecting the centers of A- and C-tubules  of the triplet of the two (brown line). *, P<0.01. n, number of triplet angles measured. Data information: Data were analyzed by unpaired t-test. The graphs show mean ± SEM.",
    "ncbi_link": "bld10: 
bld12: "
  },
  {
    "caption": "D. To determine the Akt domain responsible for interacting with INVS, Akt subfragments were generated. The C-terminus of Akt is the primary domain for INVS interaction (lanes 7-9). Similar levels of each Akt fragment were immunoprecipitated using anti-HA antibody.",
    "ncbi_link": "Akt: 208///207"
  },
  {
    "caption": "E. Schematic showing the structure and the functional domains of Flag-tagged full-length and fragmented INVS in mammalian expression vectors (N-Term: 1-421, Intermediate domain: 421-678, and C-Term: 678-1065) used in the current study. Intermediate (lanes 6-9) and C-terminal (lanes 10-12) fragments of INVS were important for interaction with Akt.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "A. The indicated recombinant INVS proteins (lanes 1-4) were used for IVK. Akt phosphorylates WT (lane5), 1-970 (lane 6), and 1-898 (lane 7) INVS, but failed to phosphorylate 1-670 (lane 8) INVS.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "Co-immunoprecipitation assays using HEK293T cells show that INVS preferentially binds to WT-Akt (second panel, lane1) or phospho-mimetic Akt (T308D/S473D, lane2), but fails to interact with phosphorylation-defective forms of Akt (T308A/S473A, lane 3).PDGF-AA stimulation of HEK293T cells results in augmented interaction of endogenous INVS with Akt (top panel, comparison between lane 1 and lane 2, untreated and PDGF-AA-stimulated conditions, respectively).",
    "ncbi_link": "Akt: 208///207"
  },
  {
    "caption": "Both WT and 3A-INVS, which are localized at the INVS compartment of primary cilia under serum-starved condition (left side panels, lower panels show higher magnification), translocate to the basal body of the cilium after PDGF-AA stimulation (right side panels, lower panels show higher magnification). Results presented are means ± SE of yellow pixels demonstrating colocalization of EGFP-INVS (green) with γ-tubulin (red) in hTERT-RPE1 cells (n=28). Three independent experiments showed similar results. Statistical significance was determined by student's t test. Fluorescence intensities of INVS (green), acetylated-α-tubulin (blue), and γ-tubulin (red) along the line (a-b) are plotted underneath.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "A. PDGF-AA stimulation resulted in the phosphorylation of WT INVS (top panel, lane 2), but not 3A INVS (top panel, lane 6). PDGF-AA-stimulated INVS phosphorylation is inhibited by Akt inhibitors (top panel, LY294002, MK2206, and GSK690693, lanes 3, 4, and 5, respectively).",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "B. Myr-Akt, a constitutively active form of Akt, was expressed together with WT or 3A INVS in HEK293 cells and INVS phosphorylation was quantified. WT, but not 3A INVS, can be phosphorylated in the presence of Myr-Akt.",
    "ncbi_link": "Akt: 208///207
INVS: 27130"
  },
  {
    "caption": "C. 3A INVS exhibited a weaker interaction with Akt as compared to WT INVS (top panel, compare lanes 1 and 2, WT and phospho-defective mutant, respectively). Expression of Akt and INVS are shown underneath.D. 3A INVS exhibited weaker dimerization as compared to WT INVS (top panel, compare lanes 1 and 2, WT and 3A, respectively). Expression of Akt and INVS are shown below each.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "E. Length of primary cilia in confluent hTERT-RPE cells was analyzed after siRNA-mediated knock down of Akt1/2. Ciliary length decreased in cells expressing siRNA. Results presented are means ±SE of the longitudinal length of acetylated-tubulin (red), a marker of primary cilia, in siRNA-transfected (green) hTERT-RPE1 cells (n=175 for control siRNA and Akt siRNA, and n=195 for Akt siRNA plus siRNA resistant Akt, respectively). Three independent experiments showed similar results. Statistical significance was analyzed by student's t test. Note that re-introduction of siRNA-resistant Akt (Matsuda-Lennikov et al., 2014) in Akt knockdown cells rescued the effect on ciliary length.",
    "ncbi_link": "Akt1: 207
Akt: 208///207"
  },
  {
    "caption": "Quantification of ciliary length. Results are mean ± SE of longitudinal length of acetylated-tubulin (blue), a marker of primary cilia, in EGFP-INVS (green) transfected in hTERT-RPE1 cells (n=58 for EGFP vector and for EGFP-INVS WT, and n=52 for EGFP-INVS 3A mutant, respectively). Three independent experiments showed similar results. Statistical significance was determined by student's t test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "Schematic describing the measurement of spindle angle (θ) (Kikuchi et al., 2010). Z-stack images were obtained from 0.45 mm-thick sections of metaphase cells and the angle between the axis of metaphase spindle and that of the substrate surface, which is termed the spindle angle, was calculated. Results presented are scatter plots of the angle (θ) of the mitotic spindle (n=28 for all samples of vector, HA-WT, -3D, -3A, -R899X, -Q671X, and -R603X INVS stably transfected MDCK cells). Three independent experiments showed similar results. Statistical significance was determined by Mann-Whitney's non-parametric median test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "Spindle angles were measured in MDCK cells transfected with the indicated INVS plasmids (+). The spindle axis was misaligned in cells expressing mutant forms of INVS as compared to cells expressing WT INVS or sham-transduced cells. Expression of 3A INVS and of clinically relevant truncated forms of INVS but not WT INVS, resulted in disorientation of the spindle axis during metaphase. Similar expression of all INVS constructs was verified by immunoblotting (Appendix figure S4A).",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "WT INVS robustly inhibited the transactivation of INVS in a luciferase reporter assay, which could be reverted by C-terminal truncated INVS (R899X, Q671X, or Q603X), but not by a phospho-mimetic mutant or 3A INVS. Results presented are mean ± SE of the ratio of triplicates between sequentially measured firefly TCF/LEF signal and Renilla luciferase signal in HA-INVS transfected 293T cells. Dual-Luciferase reporter® Assay System (Promega) was used and experiments were performed in triplicates. Two independent experiments showed similar results. Statistical significance was determined by student's t test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "WT INVS- transduced MDCK cells in 3D cultures form uniform round tubules. However, expression of 3A or NPHP2-related truncated INVS mutants, which lack Akt phosphorylation site (s), disrupts this uniformity. Results presented are representative of three independent experiments and show mean ± SE of percent normal acini in vector- or WT INVS-transduced MDCK cells (n=422 for Vector, n=398 for HA-WT, n=401 for -3D, n=365 for -3A, n= 344 for -R899X, n=331 for -Q671X, and n=325 for -R603X INVS stably transfected MDCK cells, respectively). Three independent experiments showed similar results. Statistical significance was determined by student's t test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "WT transduced MDCK cells form a relatively smaller lumen; however, expression of 3A INVS or the indicated NPHP2-related truncation mutants result in relatively larger acini. Both truncation mutants (Q671X or R603X) lack the Akt phosphorylation site and exhibit a larger lumen size. Three independent experiments showed similar results.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "C. Quantification of normal lumen in cells transduced with WT or mutant INVS. Results presented are mean ±SE of percent normal acini in vector- or WT INVS-transduced MDCK cells (n=166 for Vector, n=204 for HA-WT, n=233 for -3D, n=150 for -3A, n=164 for -R899X, n=128 for -Q671X, and n=137 for -R603X INVS stably transfected MDCK cells, respectively). Three independent experiments showed similar results. Statistical significance was determined by student's t test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "D. Size of lumen in cells transduced with WT or mutant INVS is shown. Results presented are scatter plots of acini size (n=205 for Vector, n=143 for HA-WT, n=131 for -3D, n=167 for -3A, n=144 for -R899X, n=128 for -Q671X, and n=144 for -R603X INVS stably transfected MDCK cells, respectively). Two independent experiments showed similar results. Statistical significance was determined by Mann-Whitney's non-parametric median test.",
    "ncbi_link": "INVS: 27130"
  },
  {
    "caption": "A. Time-lapse of actin filaments constantly exposed to nGr-Tpm1.8 (yellow), WT mCh-cofilin-1 (blue) and S3D-cofilin-1, and to MICAL1 from time t=100s onwards. Here we mixed WT with an excess of S3D-cofilin-1 to mimic cellular conditions in which most of cofilin-1 is inhibited by phosphorylation. While Tpm prevents cofilin from binding to non-oxidized filaments, MICAL1 rapidly oxidizes actin, allowing cofilin to bind and sever filaments.",
    "ncbi_link": "mCh: "
  },
  {
    "caption": "(A) MEFs were transfected with GFP-tagged wild-type (WT) or mutant Parkin expression plasmid followed by an 18-h treatment of CCCP. Cells are immunostained with a Tom20 antibody to visualize mitochondria (red). GFP-parkin-transfected cells are marked by dotted lines. Arrows indicate parkin-positive mitochondria or mitochondrial aggregates. Bar, 10 µm. (B) The average percentages of mitochondria-free cells from three independent experiments from A are presented with standard deviation as error bar. **, P < 0.01",
    "ncbi_link": "Parkin: 56816"
  },
  {
    "caption": "(C) MEFs were transfected and treated with CCCP as described in A, followed by an immunoblotting analysis with antibodies for cytochrome c, actin, and parkin. Note that levels of parkin R275W and R42P mutant were lower, as previously reported (Wang et al., 2005).",
    "ncbi_link": "parkin: 56816"
  },
  {
    "caption": "CCCP-induced parkin-mitochondrial aggregate formation is an intermediate step for mitophagy. (A) MEFs expressing WT GFP-parkin were treated with CCCP or CCCP and nocodazole (NOC, 10 µM) for 8, 16, and 24 h as indicated. Cells were immunostained with anti-Tom20 to visualize mitochondria. GFP-parkin-positive cells are marked by dotted lines. Arrows indicate parkin-positive mitochondria or mitochondrial aggregates. Bar, 25 µm. (B) The average percentages of cells with mitochondrial aggregates or without mitochondria from three independent experiments from A are presented with standard deviation as error bar. **, P < 0.01.",
    "ncbi_link": "parkin: 56816"
  },
  {
    "caption": "(A) MEFs were transfected with GFP wild-type (WT), A240R, and T415N mutant parkin followed by CCCP treatment for 8 h. Cells were immunostained with antibodies for cytochrome c (red) and ubiquitin (blue). Arrows indicate mitochondrial aggregates. Bar, 10 µm. (B) The average percentages of ubiquitin-positive mitochondrial aggregates from three independent experiments from A are presented with standard deviation as error bar.",
    "ncbi_link": "parkin: 56816"
  },
  {
    "caption": "Parkin-mediated ubiquitination recruits p62 and HDAC6. MEFs were transfected with WT, A240R, and T415N mutant GFP-parkin followed by CCCP treatment for 8 h. Cells were double immunostained with cytochrome c (red) and p62 antibody (blue) in A, and cytochrome c (red) and HDAC6 antibody in C. Arrows indicate mitochondrial aggregates. (B and D) The average percentages of p62- or HDAC6-positive mitochondrial aggregates from three independent experiments are presented with standard deviation as error bar.",
    "ncbi_link": "Parkin: 56816"
  },
  {
    "caption": "Parkin-mediated ubiquitination recruits p62 and HDAC6. MEFs were transfected with WT, A240R, and T415N mutant GFP-parkin followed by CCCP treatment for 8 h. Cells were double immunostained with cytochrome c (red) and p62 antibody (blue) in A, and cytochrome c (red) and HDAC6 antibody in C. Arrows indicate mitochondrial aggregates. (B and D) The average percentages of p62- or HDAC6-positive mitochondrial aggregates from three independent experiments are presented with standard deviation as error bar.",
    "ncbi_link": "Parkin: 56816"
  },
  {
    "caption": "(E) Wild-type and HDAC6 knockout (KO) MEFs were transfected with parkin-GFP or cotransfected with a Flag-tagged HDAC6 followed by CCCP treatment for 16 h as indicated. Cells are immunostained with Tom20 (red) and Flag (blue) antibodies. Bar, 25 µm.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "(F) Wild-type MEFs were transfected with control or HDAC6 siRNA and parkin-GFP, and treated with or without CCCP for 16 h. Cell lysates were subjected to immunoblotting analysis using antibodies for Tom20, parkin, HDAC6, and actin.",
    "ncbi_link": "HDAC6: 15185"
  },
  {
    "caption": "MEFs were transfected with control or cortactin RNAi and parkin-GFP, and incubated with or without CCCP for 16 h as indicated. (A) Cells were subjected to immunostaining with antibodies for Tom20 and parkin. Bar, 10 µm.",
    "ncbi_link": "cortactin: 13043
parkin: 56816"
  },
  {
    "caption": "MEFs were transfected with control or cortactin RNAi and parkin-GFP, and incubated with or without CCCP for 16 h as indicated.(B) Cell lysates were subjected to immunoblotting with antibodies for Tom20, parkin, cortactin, and actin.",
    "ncbi_link": "cortactin: 13043
parkin: 56816"
  },
  {
    "caption": "(D-F) THP-1 cells stably expressing the nucleocapsid gene or control vector were stimulated with 10 μM nigericin for 30 min following pretreatment with 1 μg/ml LPS for 3 h. Supernatants and cell pellets were collected and  immunoblotted  with antibodies against the indicated proteins (D). The percentage of viable cells was determined through checking cellular ATP  levels in cell pellets (E). The percentage of cells undergoing pyroptosis  was calculated through checking released  LDH in the supernatants (F). For E, F, Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; NS, non-significant. Data information: control vector used here was empty vector corresponded to the nucleocapsid-containing vector. Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; NS, non-significant. Similar results were observed for at least three times.",
    "ncbi_link": "nucleocapsid: 43740575"
  },
  {
    "caption": "(D) GSDMD+/+ and GSDMD-/- THP-1  cells were transfected with plasmids encoding nucleocapsid for 24 h, followed by cell fixation, permeabilization and stain  with antibodies against nucleocapsid  and GSDMD. The nucleus was counterstained  with DAPI. Scale bar: 5 μm.",
    "ncbi_link": "GSDMD: 79792
nucleocapsid: 43740575"
  },
  {
    "caption": "(E, F) THP-1  (E) or   human CD14+ monocytes  (F) were transfected with plasmids encoding  FLAG-tagged nucleocapsid  for 36 h, followed by pretreatment of 1 μg/ml  LPS  for 3 h and 10 μM nigericin stimulation for 30 min. Cells were lysed and  immunoprecipitated with antibody against FLAG or isotype IgG. Input and precipitates were immunoblotted  as indicated.",
    "ncbi_link": "FLAG: 
nucleocapsid: 43740575"
  },
  {
    "caption": "(A, B) THP-1  cells stably expressing  nucleocapsid or control vector were stimulated with 10 μM  nigericin for 30 min following pretreatment with 1 μg/ml LPS for 3 h. Cells were either immunoblotted  with antibodies against the indicated proteins (A) or stained with propidium iodide (PI) (B, left). Scale bar: 20 μm. The percentage of PI positive cells was calculated (B, right). Student's t-test was used and data were shown as means±SD of three technical replicates. ***, P<0.001; NS, non-significant. Results were repeated for three times with similar results. Data information: control vector used here was empty vector corresponded to the  nucleocapsid-containing vector. Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; ***, P<0.001; NS, non-significant. Similar results were observed for at least three times.",
    "ncbi_link": "nucleocapsid: 43740575"
  },
  {
    "caption": "(H, I) THP-1  cells stably expressing full-length  nucleocapsid  or mutant lacking amino acids 70-160 and 290-360 were stimulated with 10 μM nigericin  for 30 min following pretreatment with 1 μg/ml LPS for 3 h. Cells were either immunoblotted  with antibodies against the indicated proteins (H). Cells were also stained with  PI  and the percentage of  PI  positive cells was calculated (I). Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; NS, non-significant. Results were repeated for three times with similar results. Data information: control vector used here was empty vector corresponded to the  nucleocapsid-containing vector. Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; ***, P<0.001; NS, non-significant. Similar results were observed for at least three times.",
    "ncbi_link": "nucleocapsid: 43740575"
  },
  {
    "caption": "GSDMD-/- THP-1  cells rescued with wild-type or linker substituted GSDMD were transfected with plasmids encoding  nucleocapsid  or control vector and then stimulated with 10 μM nigericin  for 30 min following pretreatment with 1 μg/ml  LPS for 3 h. Cells were  immunoblotted  with antibodies against the indicated proteins (A)",
    "ncbi_link": "GSDMD: 79792
nucleocapsid: 43740575"
  },
  {
    "caption": "(E, F) GSDMD-/- THP-1 cells rescued with wild-type or linker substituted GSDMD  were infected with SARS-CoV-2 at an MOI of 1 for 1h, followed by washing away extracellular viruses and further culture for 3 h. Otherwise, cells were stimulated with 10 μM nigericin  for 30 min following pretreatment with 1 μg/ml LPS for 3 h. Supernatants were subjected to an ELISA assay to determine  IL-1β levels (E). Otherwise, cell viability in cell pellets was examined using a cell viability assay  through checking  ATP levels inside cells (F). For E, F, Student's t-test was used and data were shown as means±SD of three technical replicates. **, P<0.01; ***, P<0.001; NS, non-significant. Results were repeated for three times with similar results.",
    "ncbi_link": "GSDMD: 79792"
  },
  {
    "caption": "C Quantitative RT-PCR detection of glycolytic gene expression levels in HaCaT cells upon miR-31 overexpression. β-actin was used as a house-keeping control gene (n=3 biological replicates)",
    "ncbi_link": "β-actin: 60
miR-31: 407035"
  },
  {
    "caption": "G and H Glycolysis stress test of HaCaT cells upon UK5099 (G, n=4 biological replicates) or PC siRNA (si-PC, H, n=5 biological replicates) in 1mM glucose condition. ECAR and OCR were normalized to the amount of protein.",
    "ncbi_link": "PC: 5091"
  },
  {
    "caption": "B Western blot analysis of GLS, GS, GOT1, GOT2, AGC1 in HaCaT cells upon miR-31 overexpression, Tubulin α was used as loading control.",
    "ncbi_link": "miR-31: 407035"
  },
  {
    "caption": "C Quantitative RT-PCR detection of Has-miR-31-5p expression levels in HaCaT cells exposed to a range of glucose (n=4 biological replicates). RNU6-1 was used as house control gene.",
    "ncbi_link": "Has-miR-31-5p: 407035
RNU6-1: 26827"
  },
  {
    "caption": "D Western blot analysis of GS in HaCaT cells with miR-31 overexpression under different concentrations of glucose or 2-DG treatment, and Tubulin α was used as a loading control.",
    "ncbi_link": "miR-31: 407035"
  },
  {
    "caption": "A Representative picture of in situ hybridization (ISH) staining of miR-31 in skin biopsies of healthy individuals and psoriasis patients (n=5 individuals in each group). Quantification of results showing the average level of miR-31 in skin epidermis (right panel). B, basal layer; S+G, spinous and granular layers. Scale bars: 100 μm.",
    "ncbi_link": "miR-31: 407035"
  },
  {
    "caption": "J Quantitative RT-PCR detection of mmu-miR-31-5p expression levels in skin of mice (n=5 mice in each group).",
    "ncbi_link": "mmu-miR-31-5p: 723895"
  },
  {
    "caption": "• A Assessment of proteolytic activity present in culture media of human embryonic kidney 293T cells transfected with cDNA encoding PAPP-A2, PAPP-A2(D643fs) (family 1), or PAPP-A2(A1033V) (family 2). Radiolabeled substrates tested include IGFBP-3, IGFBP-4, and IGFBP-5. Cleavage was visualized by autoradiography following SDS-PAGE. Positions of intact IGFBPs (i) and cleavage products (c) are indicated.",
    "ncbi_link": "PAPP-A2: 60676"
  },
  {
    "caption": "•C Comparison of proteolytic activity similar to the experiment of panel A, except that equimolar concentrations of PAPP-A2 and PAPP-A2 (A1033V) were used. The variant from Family 1, carrying a frameshift mutation N-terminal to the proteolytic domain of PAPP-A2, did not show any detectable expression. All gels and blots are representative of three independent experiments.",
    "ncbi_link": "PAPP-A2: 60676"
  },
  {
    "caption": "(d) An FP assay using FITC-labelled Galbi peptides, including mutants (L374A, Y380F and Y380A) against an increasing concentration of GAL8. (e) An FP assay using a FITC-labelled Galbi peptide against an increasing concentration of GAL8 mutants (E268A, I270A, Y272A and Trp317). (d,e) The KD values were calculated from at least three independent experiments. ND, not determined.",
    "ncbi_link": "Galbi: 10241
GAL8: 3964"
  },
  {
    "caption": "Immunoblotting and (D) quantification of the stability of four STOP target proteins in both G1S and natural mitotic cells treated with BCL9 siGenome pools and CHX (n=3).",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "Representative pictures (left panel) and the normalised biosensor intensity based on live cell imaging of the cells with a GSK3-GFP biosensor following different treatments before and after metaphase (n=10). Scale bars represent 10 μm.",
    "ncbi_link": "GFP: 
GSK3: "
  },
  {
    "caption": "Myc and β-catenin target gene enrichment analysis based on the transcriptome targets regulated by BCL9.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "The representative xenograft tumours (top panel) and tumour growth analysis (bottom panel) of scramble and BCL9 stable knockdown cells. LF: left flank of mouse, RF: right flank. n=6 for shS1 vs. shB1, n=5 for shS1 vs. shB2.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "Confocal (left panel) and live cell imaging (right panel) analysis of chromosome segregation in H2BGFP-cells following siRNA treatment; yellow arrows indicate the typical abnormal chromosomes by BCL9 knockdown. 23 H2BGFP-mitotic cells were monitored for each time experiment; data are shown from three independent experiments. Scale bars represent 5 μm. Quantification of aberrant chromosome segregation rate by live cell imaging of H2BGFP cells upon Wnt3a or DKK1 treatment. 23 H2BGFP-mitotic cells were monitored for each time experiment; data are shown from three independent experiments.",
    "ncbi_link": "GFP: 
BCL9: 607
H2B: 128312///114483833///255626///8339///85236///158983///8340///3017///8341///8344///8342///8345///8348///8343///3018///8346///440689///100101478///337874///100288742///100820735///102724334///767811///54145///10340///337872///338391///337875///337873///286436///8970///8347///8349
H2B: 114483833///255626///128312///8339///85236///158983///8340///3017///8341///8344///8342///8345///8348///8343///3018///440689///8346///337874///100288742///100101478///100820735///767811///54145///10340///102724334///337872///338391///337875///337873///286436///8970///8347///8349
H2B: 114483833///255626///128312///8339///85236///158983///8340///8341///3017///8344///8342///8345///8348///8343///3018///440689///8346///337874///100288742///100101478///54145///100820735///767811///10340///102724334///338391///337872///337875///337873///286436///8970///8347///8349"
  },
  {
    "caption": "Quantification of the duration of NEB to ANA (NEB: nuclear envelope breakdown, ANA: anaphase), NEB to cell death in interphase after cell division (blue colour bar) or in mitosis (dark red bar), or growth well in 30 hours (pink bar) by live cell imaging analysis in monitored H2BGFP cells with different treatments.",
    "ncbi_link": "GFP: 
H2B: 114483833///255626///128312///8339///85236///158983///8340///3017///8341///8344///8342///8345///8348///8343///3018///440689///8346///337874///100288742///100101478///767811///100820735///54145///10340///102724334///337872///338391///337875///337873///286436///8970///8347///8349"
  },
  {
    "caption": "Duolink analysis (A) and its quantification (B) of the interaction by assessing the PLA complex in mitotic cells after BCL9 or Axin1 knockdown (n=20). Scale bars represent 5 μm.",
    "ncbi_link": "Axin1: 8312
BCL9: 607"
  },
  {
    "caption": "Immunoprecipitation analysis of the BCL9-MF interaction in CLTC knockdown mitotic cells.",
    "ncbi_link": "CLTC: 1213"
  },
  {
    "caption": "Immunoprecipitation analysis of the endogenous clathrin interaction with LRP6 signalosome components in BCL9 MF-overexpressing mitotic cells.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "Immunoblotting analysis of signalosome components by immunoblotting in BCL9, CLTC or in both BCL9 and CLTC knockdown mitotic cells with CHX. Quantification of the stability of several LRP6 signalosome components by immunoblotting of mitotic cells with CHX.",
    "ncbi_link": "BCL9: 607
CLTC: 1213"
  },
  {
    "caption": "Immunoprecipitation analysis of transiently-expressed BCL9-MF or T172A-MF interactors in synchronised cells, from G1S to G2 M phase. The relative level of BCL9-MF or T172A-MF immunoprecipitation is determined; red numbers indicate up-regulation, and green numbers indicate down-regulation compared to the starting time point.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "Immunoprecipitation analysis of the transiently-expressed BCL9-MF interaction in mitotic cells treated with RO3306.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": "Log-rank (Mantel-Cox) survival analysis based on high and low p-T172-BCL9 expression scored by immunohistochemical staining in two tissue arrays with (G) 75 lung cancer samples or (H) 145 breast cancer samples.",
    "ncbi_link": "BCL9: 607"
  },
  {
    "caption": " (B) HeLa-GFP-Parkin cells were transfected with siNDP52 or scrambled siRNA. Seventy-two hours after transfection, cells were incubated with 1 µM valinomycin for the indicated times. Western blotting was performed using the indicated antibodies. Data are representative of three independent experiments ",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": " (D) Fluorescence images of NDP52 KD and control cells expressing mCherry-LC3 and MTS-TagBFP. Arrows indicate mCherry-LC3 puncta colocalized with MTS-TagBFP. Scale bars, 10 µm. Boxed areas in images are shown in the next panels on the right. Images are representative of four independent experiments ",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(E) Mitophagic flux in NDP52 KD cells expressing siRNA-resistant NDP52 or NDP52 mutants. Cells were incubated with valinomycin for 3 h. Results are the summary of three independent experiments. Values are the means ± SEM. *p < 0.05, **p < 0.01 vs scrambled oligo-transfected cells; †p < 0.05, ††p < 0.01 vs empty vector-transfected cells, determined with one-way ANOVA followed by the Tukey-Kramer post hoc test",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(F) HeLa-GFP-Parkin cells expressing mCherry-NDP52 mutants were incubated with 1 µM valinomycin and 100 nM bafilomycin A1 for 3 h. Cell lysates were subjected to immunoprecipitation using anti-RFP magnetic beads. Immunoprecipitates were analyzed by western blotting. Data are representative of three independent experiments",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(G) Images of HeLa GFP-Parkin cells expressing mCherry-NDP52∆LIM-L or mCherry-NDP52∆SKICH treated with valinomycin for 2h. The images are from Movie EV 4. Cyan, GFP-Parkin; magenta, mCherry-NDP52 mutant. Scale bars, 10 µm. Images are representative of three independent experiments",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(A) Mitophagic flux in cells transfected with siNDP52, siTBK1, siOPTN or a combination of siRNAs. Results are the summary of three independent experiments. Values are the means ± SEM. **p < 0.01 vs scrambled oligo-transfected cells; †p < 0.05 vs siNDP52-transfected cells; §p < 0.05, §§p < 0.01 vs siTBK1; NS: not significant, determined with one-way ANOVA followed by the Tukey-Kramer post hoc test",
    "ncbi_link": "NDP52: 10241
OPTN: 10133
TBK1: 29110"
  },
  {
    "caption": "(B) HeLa-GFP-Parkin cells transfected with siNDP52, siOPTN, siTBK1 or scrambled siRNA were incubated with 1 µM valinomycin for the indicated times. Cell lysates were subjected to SDS-PAGE or Phos-tag-PAGE prior to western blotting using the indicated antibodies. Data are representative of two independent experiments. The position of phosphorylated forms of NDP52 or OPTN are indicated by arrowheads",
    "ncbi_link": "NDP52: 10241
OPTN: 10133
TBK1: 29110"
  },
  {
    "caption": "(C) Images of TBK1 KD cells expressing mCherry-NDP52 or mCherry-OPTN under valinomycin treatment from Movie EV 5. Cyan, GFP-Parkin; magenta, mCherry-NDP52. Images are representative of two independent experiments. Scale bars, 10 µm",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "(D) TBK1 KD and control cells expressed mCherry-NDP52. Lysates were subjected to immunoprecipitation using anti-RFP beads. Immunoprecipitates were analyzed by western blotting. Data are representative of three independent experiments",
    "ncbi_link": "TBK1: 29110"
  },
  {
    "caption": "Anti-RFP immunoprecipitates from mCherry-NDP52 and mCherry-NDP52 ∆SKICH-transfected cells were subjected to SDS-PAGE followed by silver staining. Four bands specific for mCherry-NDP52 are numbered and were identified by mass spectrometric analysis. Asterisk (*) and double asterisk (**) indicate mCherry-NDP52 and mCherry-NDP52∆SKICH bands, respectively",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(D) HeLa-GFP-Parkin cells transfected with siMTPAP were incubated with 1 µM valinomycin for the indicated times. Western blotting was performed using the indicated antibodies. Data are representative of three independent experiments",
    "ncbi_link": "MTPAP: 55149"
  },
  {
    "caption": "(E) Mitophagic flux in cells transfected with siNDP52, siMTPAP and combinations of siRNAs. Cells were incubated with valinomycin for 3 h. Results are the summary of three independent experiments. Values are the means ± SEM. **p < 0.01 vs scrambled oligo-transfected cells; NS: not significant, determined with one-way ANOVA followed by the Tukey-Kramer post hoc test",
    "ncbi_link": "NDP52: 10241
MTPAP: 55149"
  },
  {
    "caption": "(F) Images of MTPAP KD cells expressing mCherry-NDP52 under valinomycin treatment. The images are from Movie EV 7. Cyan, GFP-Parkin; magenta, mCherry-NDP52. Images are representative of two independent experiments. Scale bars, 10 µm",
    "ncbi_link": "MTPAP: 55149"
  },
  {
    "caption": "(A, B) mCherry-LC3 and MTS-TagBFP were expressed in MTPAP KD and control cells. Cells were incubated with valinomycin for the indicated times and immunostained with anti-NDP52 antibody. Images are representative of two independent experiments. Yellow arrows indicate co-localization of MTS-TagBFP, mCherry-LC3 and NDP52. White arrows indicate co-localization of MTS-TagBFP and NDP52 (not mCherry-LC3). Scale bars, 10 µm. Co-localization of mCherry-LC3 and NDP52 on mitochondria is quantified in (B). At least ten cells from two independent experiments were quantified. Values are the means ± SEM. **p < 0.01 vs control, determined with one-way ANOVA followed by the Student"s t",
    "ncbi_link": "MTPAP: 55149"
  },
  {
    "caption": "MTPAP KD and control cells expressed mCherry-NDP52 or empty vector (C Lysates from cells treated with 1 µM valinomycin and 100 nM bafilomycin A1 for 2 h were subjected to immunoprecipitation using anti-RFP beads. Immunoprecipitates were analyzed by western blotting. Data are representative of three independent experiments",
    "ncbi_link": "NDP52: 10241
MTPAP: 55149"
  },
  {
    "caption": "MTPAP KD and control cells expresse mCherry-LC3 (D). Lysates from cells treated with 1 µM valinomycin and 100 nM bafilomycin A1 for 2 h were subjected to immunoprecipitation using anti-RFP beads. Immunoprecipitates were analyzed by western blotting. Data are representative of three independent experiments",
    "ncbi_link": "MTPAP: 55149"
  },
  {
    "caption": "(E) MTPAP KD and control cells were incubated with valinomycin and bafilomycin A1 for 2 h. Cell lysates were subjected to immunoprecipitation using an anti-NDP52 antibody or control IgG. Immunoprecipitates were analyzed by western blotting. Data are representative of three independent experiments",
    "ncbi_link": "MTPAP: 55149"
  },
  {
    "caption": "(F) GST-NDP52 conjugated with glutathione-Sepharose resin was incubated with purified recombinant LC3 and MTPAP∆MTS∆C. The pulled down complex was subjected to western blotting. Data are representative of three independent experiments",
    "ncbi_link": "NDP52: 10241
LC3: 81631///84557
MTPAP: 55149"
  },
  {
    "caption": " (A) HeLa-GFP-Parkin cells expressing mCherry-NDP52 D439R/C443K mutant or WT NDP52 were incubated with valinomycin and nM bafilomycin A1 for 3 h. Cell lysates were subjected to immunoprecipitation using anti-RFP magnetic beads. Immunoprecipitates were analyzed by western blotting. Data are representative of two independent experiments ",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": " (B) Selected frames from time-lapse images of HeLa GFP-Parkin cells expressing mCherry-NDP52 D439R/C443K mutant under valinomycin and bafilomycin A1 treatment. The images are representative of two independent experiments and correspond to the boxed regions of Movie EV 9. Cyan, GFP-Parkin; magenta, mCherry-NDP52 D439R/C443K. The white arrowheads indicate colocalization of GFP-Parkin and mCherry-NDP52. The yellow arrowheads indicate mCherry-NDP existing inside GFP-Parkin ring structures. Scale bars, 1 µm",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "α, β, indicate Atg16L1 isoform α, β; ∆CCD indicates Atg16L1∆CCD; asterisk indicates a non-specific band. Atg16L1∆/∆ indicates mice expressing ∆Atg16L1. The number of endogenous LC3 or GFP-Atg5 dots was counted (c, d). The results shown are mean + s.d. (n > 20).",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "c, IL-1b and IL-6 production by wild-type or Atg7-deficient macrophages stimulated with LPS. Statistical significance was determined by the Student's t-test. *P,0.01.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "e, f, Atg16L1-deficient chimaeric mice given 5% DSS in drinking water were intraperitoneally injected with both anti-IL-1b and anti- IL-18 neutralizing antibodies (squares; n55) or isotype control IgG (circles;n55) at days 1, 3, 5 and 7. The survival (e) and weight loss (f) of each mouse genotype were plotted.",
    "ncbi_link": "Atg16L1: 77040"
  },
  {
    "caption": "B, C WT and SKAP55−/−OT-ICD8+CTLs were generated from WT or SKAP55−/−OT-I Tg mice, then incubated with 10 nM OVA257-264-pulsed EL4 targets for 4 h to assess the in vitro cytotoxicity at different Effector:Target ratios (B; mean of triplicates ± SD); surface expression and the mRNA levels of PD-1 (C). Graphs are representative of at least three independent experiments.",
    "ncbi_link": "PD-1: 18566
SKAP55: 78473"
  },
  {
    "caption": "D WT and SKAP55−/− OT-I CD8+ CTLs (3 × 106) were injected into C57BL/6 mice, followed by injection of non-pulsed (CFSEhi) or 10 nM OVA257-264-pulsed (CFSElo) splenocytes (5 × 106) to measure in vivo cytotoxicity (mean ± SD, n = 3 mice per group). Representative data of three independent experiments.",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "E WT and SKAP55−/− OT-I CD8+ CTLs were pretreated with anti-PD-1 antibody or IgG control, followed by incubation with OVA257-264-pulsed EL4 cells to examine in vitro killing ability (mean of triplicates ± SD). Graphs are representative of three independent experiments.",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "F CD8+ CTLs were transfected with plasmids expressing SKAP55-GFP or EGFP, then treated with non-pulsed or 10 nM OVA257-264-pulsed EL4 cells to examine surface PD-1 expression (left panel) or the in vitro killing assay (mean of triplicates ± SD) (right panel).",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "B OT-I CD8+ CTLs were transfected with plasmids expressing ADAP or GFP, then stimulated with 10 nM OVA257-264-pulsed EL-4 cells to detect surface PD-1 expression. Representative of three independent experiments.",
    "ncbi_link": "ADAP: 23880"
  },
  {
    "caption": "C, D WT and ADAP−/− OT-I CD8+ CTLs were stimulated with 10 nM OVA257-264-pulsed or unpulsed EL-4 cells for 4 h to examine surface expression and the mRNA levels of PD-1 (C), in vitro cytotoxicity at different Effector:Target ratios (D; mean of triplicates ± SD). Graphs are representative of at least three independent experiments.",
    "ncbi_link": "ADAP: 23880
PD-1: 18566"
  },
  {
    "caption": "E WT and ADAP−/− OT-I CD8+ CTLs were pretreated with 10 μg/ml anti-PD-1 antibody or IgG control, followed by incubation with 10 nM OVA257-264-pulsed EL4 cells to examine in vitro killing ability (mean of triplicates ± SD).",
    "ncbi_link": "ADAP: 23880"
  },
  {
    "caption": "F Naïve CD8+ T cells were isolated from WT, SKAP55−/−, ADAP−/−, and SKAP55−/−ADAP−/− splenocytes, then stimulated with plate-bound anti-CD3/CD28 for 12 h to assess PD-1 mRNA levels, and for 48 h to check surface PD-1 expression (mean of triplicates ± SD).",
    "ncbi_link": "ADAP: 23880
PD-1: 18566
SKAP55: 78473"
  },
  {
    "caption": "A-C WT, ADAP−/−, or SKAP55−/− OT-I CD8+ CTLs were stimulated with OVA257-264-pulsed or unpulsed EL4 cells to detect the levels of NFATc1 expression, activation and nuclear entry by immunoblotting (A) or immunostaining (B). Alternatively, nuclear extracts from these CTLs were incubated with the N1 DNA probes containing NFAT-binding sites for an EMSA. The unlabeled competitor probe (Comp. N1) and the mutant probe that contains the same sequence except for carrying a mutated NFAT-binding site (Comp. mutN1) were included as controls (C).",
    "ncbi_link": "NFAT: 
ADAP: 23880
SKAP55: 78473"
  },
  {
    "caption": "D WT, ADAP−/−, or SKAP55−/− OT-I CD8+ CTLs were pretreated with DMSO or 5 μM CsA, then stimulated with OVA257-264-pulsed EL-4 cells for 4 h to examine surface PD-1 expression (mean of triplicates ± SD).",
    "ncbi_link": "ADAP: 23880
SKAP55: 78473"
  },
  {
    "caption": "E WT, ADAP−/−, or SKAP55−/− OT-I CTLs were pretreated with the DMSO control, 10 μM PP2 or 75 μM 2APB, then stimulated with OVA257-264-pulsed EL-4 cells for 4 h to examine surface PD-1 expression (mean of triplicates ± SD).",
    "ncbi_link": "ADAP: 23880
SKAP55: 78473"
  },
  {
    "caption": "F GFP, ADAP, or SKAP55 was overexpressed with pGL3-NFAT Luciferase reporter plasmid into Jurkat cells. Cells were stimulated with anti-CD3 and anti-CD28 in the presence or absence of PP2 or 2APB for 6 h, followed by measuring luciferase readings (mean of triplicates ± SD).",
    "ncbi_link": "Luciferase: 
luciferase: 
NFAT: 
ADAP: 2533
SKAP55: 8631"
  },
  {
    "caption": "A WT and SKAP55 KO C57BL/6 mice were s.c. immunized on day −14 and day −7 by DCs that were prepulsed with B16F10 tumor lysates. On day 0, the immunized mice were i.v. inoculated with B16F10 cells. Number of lung tumors were counted 26 days after B16F10 challenge (n ≥ 5 mice).",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "D, E The mRNA levels of PD-1, NFATc1, or the mRNA and protein levels of granzyme B in lung infiltrating CD8+ T cells were examined at day 26 (mean of triplicates ± SD, and the mRNA samples were prepared from at least 3 mice per group).",
    "ncbi_link": "granzyme B: 14939
NFATc1: 18018
PD-1: 18566"
  },
  {
    "caption": "A The same procedures as in Fig4A were performed with WT and ADAP−/− C57BL/6 mice. HE staining of lung tissue was examined on day 26 (representative graph of 5 mice).",
    "ncbi_link": "ADAP: 23880"
  },
  {
    "caption": "A, B WT and SKAP55−/− mice were s.c. injected with MO5 melanoma cells followed by two injection at day 7 and day 14 of OVA257-264-pulsed DCs or the PBS control respectively (n ≥ 5). The growth of tumors under skin was measured every three days according to tumor diameter (mean ± SEM, n ≥ 5 mice per group) (A). Surface expression levels of PD-1 were checked on OVA257-264-specific Vα2high/Vβ5+ CD8+ effector cells at day 30 (mean ± SD, n ≥ 5 mice) (B).",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "C WT and SKAP55−/− mice were s.c. injected with MO5 melanoma cells followed by s.c. two injection of OVA257-264-pulsed DCs at day 7 and day 14. anti-PD-1 monoantibody or IgG controls were i.v. injected three times at day 7, day 10, and day 14 (50 μg/injection). The diameter and volume of tumors were measured every three days (mean ± SEM, n ≥ 5 mice).",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "D The WT recipient mice were s.c. injected with MO5 melanoma cells followed by injection of 10 nM OVA257-264-stimulated WT or SKAP55−/− CTLs at day 8 (n ≥ 8). The diameter and volume of tumors were measured every three days (mean ± SEM, n ≥ 8 mice).",
    "ncbi_link": "SKAP55: 78473"
  },
  {
    "caption": "(A) EAE severity in 6-to-8-week-old female (left panel) and male (right panel) wild-type (WT) and ERα-/- mice (n=7-9 mice per group). (B) EAE sensitivity to IFNβ in 6-to-8-week-old female (top panel) and male (bottom panel) WT and ERα-/- mice. Vehicle (Veh) or IFNβ (47 μg/kg) were i.p. injected. every other day from 0 to 10 dpi (n= 8-12 mice per group).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "(D) Sensitivity of EAE to IFNβ in Cyp19-/- ovary-transferred female WT mice and WT ovary-transferred Cyp19-/- mice (n=5-6 mice).",
    "ncbi_link": "Cyp19: 13075"
  },
  {
    "caption": "(A) Brightfield micrograph of ventral horns of Golgi-Cox stained lumber (L)5 spinal cord section of male WT and ERα-/- EAE mice at 33 dpi with quantitation of area stained in gray matter. The white dotted line indicates the division between white and gray matter, V.H. represents the ventral horn (n=5 mice per group).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "(C) Representative confocal reflection maximum intensity projection micrograph of Golgi-Cox stained dendrites in the lumbar ventral horn of male WT and ERα-/- mice at 33 dpi with quantitative analysis of dendrite spine density (n=4-5 mice per group, 20 dendrites analyzed per animal).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "(A) Upregulated and downregulated genes in RNAseq analysis were evaluated by qPCR. Splenic CD4+ T cells from male WT EAE and ERα-/- EAE mice at 9 dpi were used (n=5-8 mice).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "(D) Neurite outgrowth of the neurons in Golgi-stained spinal sections of Tcra-/- recipient mice that received passive intrathecal injections of CD4+ splenic cells from male WT EAE and ERα-/- EAE mice at 14 dpi quantified using the Sholl technique. Sholl rings are separated by 10 μm (n=4 mice per group, 20 neurons analyzed per animal) with an end radius of 100 μm.",
    "ncbi_link": "ERα: 13982
Tcra: 21473"
  },
  {
    "caption": "(C) Neurite outgrowth of the neurons in Golgi-stained spinal sections of Tcra-/- recipient mice that received passive intrathecal injections of CD4+ splenic cells from male WT EAE and cERα-/- EAE mice at 14 dpi quantified using the Sholl analysis method. Sholl rings are separated by 10 μm (n=4 mice per group, 20 neurons analyzed per animal) with an end radius of 100 μm.",
    "ncbi_link": "ERα: 13982
Tcra: 21473"
  },
  {
    "caption": "(A) Number of membrane-bound lymphotoxin (mLT)+ DCs (derived from spleen and LNs) in male cERα-/- EAE mice at 9 dpi (n=5 mice per group). DC population were gated as Ly6G- and CD11c+ (EV Fig.1 A).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "(A) Lta mRNA expression in BMDCs developed from bone marrows of WT and ERα-/- mice 3 h after treatment with LPS (100 ng/ml) with vehicle (Veh) or PPT (1 µM) pre-treatment for 18 h (n=4 samples per group). (B) Il1b and Ifnb mRNA expression 3 h after treatment with LPS (100 ng/ml) with vehicle (Veh) or PPT (1 µM) pre-treatment for 18 h (n=4-5 samples per group).",
    "ncbi_link": "ERα: 13982
Ifnb: 15977
Il1b: 16176
Lta: 16992"
  },
  {
    "caption": "(C) Representative Western blot of TRAF3 and HSC70 in WT BMDCs and ERα-/- BMDCs. TRAF3 expression in BMDCs following vehicle (Veh) or PPT (1 µM) pre-treatment for 18 h was evaluated by normalization of HSC70 (n=5-7 per group).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Wild type, mps1-3 and mps1-1 mutant cells were synchronised in G1 with α-factor at permissive temperature (25°C) and then released at restrictive temperature (34°C, t=0). Cells were collected at the indicated time points for FACS analysis of DNA contents (C)",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "Wild type, mps1-3 and mps1-1 mutant cells were synchronised in G1 with α-factor at permissive temperature (25°C) and then released at restrictive temperature (34°C, t=0). Cells were collected at the indicated time points for immunofluorescence using anti-tubulin antibodies in order to score metaphase and anaphase spindles (D). Budding and nuclear division were scored on the FACS samples.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "F: Wild type and mps1 mutant cells bearing the TetO/TetR-GFP system to mark the centromere of chromosome V [43] and expressing the SPBs marker Spc97-mCherry were synchronised as in (C-D) and arrested in anaphase through the temperature-sensitive cdc15-2 allele. At 120 and 150 minutes, cells were fixed for scoring chromosome V segregation (n≥172). Arrowheads indicate the sister chromatids of chromosome V. Error bars: SD. N=3. Representative images of cells for each genotype are shown on the right. Scale bar: 5 μm.",
    "ncbi_link": "cdc15: 
mps1: 851533"
  },
  {
    "caption": "G: Wild type and mps1-3 mutant cells carrying the TetO/TetR-GFP markers for CEN5 labelling and expressing mCherry-Tub1 were grown at 25°C and then shifted to 34°C for 1 hour before filming. Cells were filmed at 34°C every 2 minutes by time lapse fluorescence microscopy. DIC: differential interference contrast. Scale bar: 5 μm.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "A: Wild type and mps1 mutant cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the presence of nocodazole (t=0). Cells were collected at the indicated time points for FACS analysis of DNA contents.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "D: Wild type and mps1-3 cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the presence of nocodazole. Cells were collected after 90 minutes and fixed with formaldehyde for ChIP-seq analysis. ChIP sequence reads were normalised against sequence reads from corresponding input samples, and relative enrichment is plotted for chromosome III around the centromere (see the centromeric regions of all 16 yeast chromosomes in Fig. S2). Y‐axis shows enrichment values (linear scale, range is 0-10). Values below 1.5 are shown in grey, and values above 1.5 (i.e. sequences enriched in ChIP samples) are red coloured.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "G-H: Cells with the indicated genotypes carrying the TetO/TetR-GFP markers for CEN5 labelling and expressing mCherry-Tub1 were grown at 25°C and then shifted to 34°C for one hour before filming. Cells were filmed at 34°C every 2 or 4 minutes by time lapse fluorescence microscopy. Chromosome V segregation errors are reported in the table (H). Representative cells are shown as examples in the montages (G). Representative montages for wild type and mps1-3 cells are shown in Fig. 1F. DIC: differential interference contrast. Scale bar: 5 μm.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "I: Wild type, mps1-3, mps1-3 spc105-18, and mps1-3 GLC7-24 cells were synchronised in G1 with α-factor at 25°C and then released at 32°C in the presence of nocodazole (note that the presence of 3HA tags at the C-terminus of Mps1-3 slightly decreases the maximal temperature of suppression). Cells were collected after 90 minutes and fixed with formaldehyde for ChIP-seq analysis. ChIP sequence reads were normalised against sequence reads from corresponding input samples, and relative enrichment is plotted for chromosome III around the centromere (see the centromeric regions of all 16 yeast chromosomes in Fig. S5). Y‐axis shows enrichment values (linear scale, range is 0-10). Values below 1.5 are shown in grey, and values above 1.5 (i.e. sequences enriched in ChIP samples) are red coloured.",
    "ncbi_link": "HA: 
GLC7: 856870
mps1: 851533
spc105: 852787"
  },
  {
    "caption": ": Wild type and mps1-3 cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the presence (A) of nocodazole (t=0). Cells were collected at the indicated time points for western blot analysis of the indicated proteins. Equal amounts of protein extracts were loaded on two different gels, for western blot of Spc105-3PK and Clb2/Pgk1 respectively. Clb2 was used as mitotic marker and Pgk1 as loading control. Cyc: cycling cells.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "Wild type and mps1-3 cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the absence (B) of nocodazole (t=0). Cells were collected at the indicated time points for western blot analysis of the indicated proteins. Equal amounts of protein extracts were loaded on two different gels, for western blot of Spc105-3PK and Clb2/Pgk1 respectively. Clb2 was used as mitotic marker and Pgk1 as loading control. Cyc: cycling cells.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "Cells with the indicated genotypes expressing Bub1-GFP and the kinetochore marker Mtw1-Tomato were grown in SD glu 2% and then shifted to 34°C for 1 hour before filming; they were then filmed every 4 minutes by time lapse fluorescence microscopy at 34°C. Note that BUB1-GFP is synthetic lethal with mps1-3. Thus, we used mps1-3 GALs-MPS1 BUB1-GFP cells that were grown in -His RG medium at 30°C; glucose was added to the culture for 30 minutes to shut off GALs-MPS1, followed by shifting cells to SD medium at 34°C for 1 before imaging in the same medium. Montages show representative cells (C). Arrowheads indicate Bub1-GFP signals at kinetochores. DIC: differential interference contrast. Scale bar: 5 μm.",
    "ncbi_link": "GFP: 
BUB1: 853100
GALs: 852308
mps1: 851533
MPS1: 851533"
  },
  {
    "caption": "Wild type and mps1-3 cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the presence (E-F) of nocodazole (t=0). Cells were collected at the indicated time points for western blot analysis of the indicated proteins and for FACS analysis of DNA contents Equal amounts of protein extracts were loaded on two different gels, for western blot of Bub1-3HA/Cdc5 and Clb2/Pgk1 respectively. A white asterisk indicates a phosphorylated isoform of Bub1 that in wild type cells correlates with lack of chromosome biorientation. Cdc5 and Clb2 were used as mitotic marker and Pgk1 as loading control. Cyc: cycling cells.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "Wild type and mps1-3 cells were synchronised in G1 with α-factor at 25°C and then released at 34°C in the absence (G-H) of nocodazole (t=0). Cells were collected at the indicated time points for western blot analysis of the indicated proteins and for FACS analysis of DNA contents (F, H). Equal amounts of protein extracts were loaded on two different gels, for western blot of Bub1-3HA/Cdc5 and Clb2/Pgk1 respectively. A white asterisk indicates a phosphorylated isoform of Bub1 that in wild type cells correlates with lack of chromosome biorientation. Cdc5 and Clb2 were used as mitotic marker and Pgk1 as loading control. Cyc: cycling cells.",
    "ncbi_link": "mps1: 851533"
  },
  {
    "caption": "A: SPC105-GBD cells expressing Bub1-GFP were grown at 30°C and filmed every 4 minutes at 30°C by time lapse fluorescence microscopy. DIC: differential interference contrast. Scale bar: 5 μm.",
    "ncbi_link": "SPC105: 852787"
  },
  {
    "caption": "(A) Immunohistochemistry for p75NTR in hippocampal CA1 of 5 month wild type, 5xFAD and p75NTR knock-out (KO) mice. Scale bar, 20μm.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(D) Immunostaining for Aβ plaques with 6E10 antibody in coronal sections through the hippocampus of 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A mice of the indicated ages. Scale bar, 400μm. (E) Quantification of Aβ plaque burden in the hippocampus of 5xFAD mouse strains carrying different p75NTR variants as indicated. Histogram shows the percentage of hippocampal area occupied by Aβ plaques (mean ± SEM, N=5 mice per group). *, P<0.05 and **, P<0.01 vs 5XFAD. #, P<0.05 vs 5XFAD/KO (one-way ANOVA followed by post hoc test). (F) Quantification of the number of Aβ plaques larger than 30um in diameter per um2 in coronal sections through the hippocampus of 9 month old 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A mice. Color codes are as in panel (E). Histogram shows mean ± SEM, N=4 mice per group; *, P<0.05 KO vs. knock-in genotypes. ",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "ELISA determinations of Aβ1-42 content in hippocampus of 5xFAD mouse strains carrying different p75NTR variants Aβ monomers (G) refers to the soluble fraction after Tris-buffered saline extraction",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "ELISA determinations of Aβ1-42 content in hippocampus of 5xFAD mouse strains carrying different p75NTR variants Aβ oligomers (H) to the soluble fraction after RIPA buffer extraction of the Tris-buffered saline pellet,",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "ELISA determinations of Aβ1-42 content in hippocampus of 5xFAD mouse strains carrying different p75NTR variants Aβ fibrils (I) to the soluble fraction after formic acid treatment of the RIPA pellet.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Immunostaining for Glial fibrillary acidic protein (GFAP), a marker of astrocytes, and Aβ plaques in coronal sections through the hippocampus of 6 month old wild type, 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A mice. Scale bar, 300μm. Right hand panels show high magnification of the indicated areas. Scale bar, 50μm. (B) Quantification of GFAP area in the hippocampus of wild type and 5xFAD mouse strains carrying different p75NTR variants as indicated. Histogram shows the percentage of hippocampal area occupied by GFAP immunostaining (mean ± SEM, N=5 mice per group). ",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(C) Immunostaining for Ionized calcium binding adaptor molecule 1 (Iba1), a marker of microglial cells, and Aβ plaques in coronal sections through the hippocampus of 6 month old wild type, 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A. Scale bar, 300μm. Right hand panels show high magnification of the indicated areas. Scale bar, 10μm. (D) Quantification of Iba1 area in the hippocampus of wild type and 5xFAD mouse strains carrying different p75NTR variants as indicated. Histogram shows the percentage of hippocampal area occupied by Iba1 immunostaining (mean ± SEM, N=5 mice per group). ",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(E) Immunostaining of reticulon 3 (RTN3), a marker of dystrophic neurites, and Aβ plaques in coronal sections through the hippocampus of 6 month old 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A mice. Scale bar, 40μm. (F) Quantification of RTN3-positive dystrophic neurite area in the hippocampus of 5xFAD mouse strains carrying different p75NTR variants as indicated. Histogram shows the percentage of Aβ plaque area that overlapped with RTN3 immunostaining (mean ± SEM, N=5 mice per group).",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(G) MitoSox staining, a mitochondrial superoxide indicator, and DAPI in coronal sections through the hippocampus of 6 month old wild type, 5xFAD, 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A mice. Scale bar, 60μm. (H) Quantification of MitoSOX signal in the pyramidal cell layer of hippocampus of wild type and 5xFAD mouse strains carrying different p75NTR variants as indicated. Histogram shows MitoSox mean fluorescence intensity in arbitrary units (mean ± SEM, N=5 mice per group).",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Percentage of change in field excitatory postsynaptic potential (fEPSP) recorded after theta-burst stimulation (TBS) in Schaffer collaterals of hippocampal slices from 6 month old wild type, 5xFAD and 5xFAD/p75NTR mutant mice, as indicated. Results are presented as mean % change normalized to t=0 ± SEM. N=6 (wild type), 5 (5xFAD), 9 (5xFAD/KO), 7 (5xFAD/ΔDD) and 8 (5xFAD/C259A) slices from 3 mice per genotype, respectively. (B) Quantification of fEPSP (mean % change ± SEM) in the indicated genotypes at 3 time points. *, P<0.05; **, P<0.01 vs. 5xFAD (two-way ANOVA followed by post hoc test). N numbers as in (A).",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(C) Behavior in the novel object recognition (NOR) test of 6 month old wild type, 5XFAD and 5XFAD/p75NTR mutant mice, as indicated. Histograms show mean recognition index ± SEM during training, and 30min, 24h and 14 days after training, corresponding to measures of short term, long term and remote memory, respectively. Bar color codes are as in panel (A). *, P<0.05 vs. 5xFAD (two-way ANOVA followed by post hoc test). N=12 (wild type, 5xFAD/ΔDD and 5xFAD/C259A), 10 (5xFAD) and 8 (5xFAD/KO) mice per genotype, respectively.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(D) Training latency in the Barnes maze test of 6 month old wild type, 5XFAD and 5XFAD/p75NTR mutant mice, as indicated. Histograms show mean latency in seconds to find the platform hole ± SEM in 4 consecutive training sessions. Bar color codes are as in panel (A). *, P<0.05 vs. 5xFAD; #, P<0.05 vs. wild type, 5xFAD/ΔDD or 5xFAD/C259A (two-way ANOVA followed by post hoc test). N=14 (wild type and 5xFAD/ΔDD), 10 (5xFAD, (5xFAD/KO and 5xFAD/C259A) mice per genotype, respectively.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Western blot analysis of CTF beta (CTFβ) in hippocampal lysates of 9 month old 5xFAD mice carrying different p75NTR alleles detected using anti-APP-CTF antibody Arrows point to phospho-C99 and C99 CTFβ species Asterisk denotes different species of native and phosphorylated alpha and beta CTFs of lower molecular weights Lower panel shows reprobing for GAPDH. (B) Quantification (mean ± SEM) of phospho-C99/C99 CTFβ species, normalized to GAPDH and expressed relative to levels in 5xFAD mice. *, P<0.05 5xFAD vs, 5xFAD/KO; ***, P<0.001 5xFAD vs. 5xFAD/ΔDD and 5xFAD/C259A; #, P<0.05 5xFAD/C259A vs. 5xFAD/KO; §, P=0.056 5xFAD/ΔDD vs. 5xFAD/KO. N=5 mice per group.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(C) Western blot analysis of soluble APP alpha (sAPPα) in the soluble Tris-buffered saline fraction of hippocampal homogenate made from 9 moth old 5xFAD mice carrying different p75NTR alleles detected using 6E10 antibody Lower panel shows reprobing for GAPDH. (D) Quantification (mean ± SEM) normalized to GAPDH and expressed relative to levels in 5xFAD mice. *, P<0.05 5xFAD vs. 5xFAD/KO, 5xFAD/ΔDD and 5xFAD/C259A; #, P<0.05 5xFAD/C259A vs. 5xFAD/KO; §, P<0.05 5xFAD/ΔDD vs. 5xFAD/KO. N=9 mice per group.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Internalization of triple mutant hAPP in wild type, p75NTR knock-out (KO), ΔDD and C259A hippocampal neurons (15min time point). Counterstaining for p75NTR and DAPI are also shown. Scale bar, 10μm.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(B) Kinetics of internalization of triple mutant hAPP in hippocampal neurons from wild type, p75NTR knock-out (KO), ΔDD and C259A mice. Shown is mean ± SEM of percentage internalization of total surface APP (set to 100%). N=3 independent experiments each performed in duplicate; *, P<0.05 knock-in vs. KO mutants; **, P<0.01, WT vs. all other genotypes (2-way ANOVA). (C) Linear transformation of hAPP internalization kinetics shown in (B). IMAX denotes maximal internalization in %. T1/2 denotes time for half maximal internalization in minutes.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(G) Kinetics of internalization of p75NTR in hippocampal neurons from wild type, ΔDD and C259A mice. Show are mean ± SEM of percentage internalization of total surface p75NTR (set to 100%). N=3 independent experiments each performed in duplicate; *, P<0.05 knock-in mutants vs. WT (2-way ANOVA). (H) Linear transformation of p75NTR internalization kinetics shown in (G). IMAX denotes maximal internalization in %. T1/2 denotes time for half maximal internalization in minutes. ",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(I) (A) Co-immunoprecipitation between p75NTR and β-adaptin in hippocampal extracts from 6 month wild type and p75NTR mutant mice as indicated. Results shown are representative from 2 independent experiments. Molecular weights are in kDa. IP: immunoprecipitation; IB: immunoblotting; WCL, whole cell lysate.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Co-immunoprecipitation between hAPP and p75NTR in hippocampal extracts from 6 month 5xFAD and p75NTR mutant mice as indicated. Results shown are representative from 3 independent experiments. Molecular weights are indicated in kDa. IP: immunoprecipitation; IB: immunoblotting; WCL, whole cell lysate.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(B) Proximity ligation assay (PLA) between triple mutant hAPP and p75NTR in hippocampal neurons from wild type and C259A mice (first and second rows, respectively). The third row (no APP) shows control PLA reaction in neurons that did not receive hAPP lentivirus. The fourth row (KO) shows control PLA reaction in neurons from p75NTR knock-out mice infected with hAPP lentivirus. Counterstaining for MAP2 is also shown. Scale bar, 10μm.",
    "ncbi_link": "APP: 351
hAPP: 351
p75NTR: 18053"
  },
  {
    "caption": "(C) Quantification of total PLA signals in wild type and p75NTR mutant neurons in the presence or absence of hAPP lentivirus, as indicated. Values were normalized to levels in wild type neurons and are expressed as mean PLA puncta per cell ± SEM from at least 25 neurons in 3 independent experiments. (D) Quantification of cell surface PLA signals in wild type and p75NTR mutant neurons in the presence or absence of triple mutanthAPP lentivirus, as indicated. Live neuron cultures were fed with anti-mouse p75NTR and anti-hAPP antibodies on ice, washed after staining, fixed, and developed with PLA reaction. Values were normalized to levels in wild type neurons and are expressed as mean PLA puncta per cell ± SEM from at least 25 neurons in 3 independent experiments. ",
    "ncbi_link": "hAPP: 351
p75NTR: 18053"
  },
  {
    "caption": "(E) Internalization of hAPP/p75NTR PLA signals in hippocampal neurons of wild type and p75NTR mutant mice. Live neuron cultures were fed with anti-mouse p75NTR and anti-hAPP antibodies on ice, washed and plates placed at 37°C for different periods of time to allow internalization. Internalization was stopped by acid wash, followed by fixation and PLA reaction. Counterstaining for MAP2 and DAPI are also shown. Scale bar, 10μm.",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(F) Kinetics of co-internalization of hAPP and p75NTR in hippocampal neurons from wild type, ΔDD and C259A mice. Show are mean ± SEM of percentage internalization of total surface PLA signal (set to 100%). (G) Linear transformation of p75NTR internalization kinetics",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(A) Micrographs of triple mutant hAPP after 15min internalization (red), BACE1 immunocytochemistry (green) and their superimposition in wild type hippocampal neurons infected with 5xFAD hAPP lentivirus. DAPI and MAP2 staining are shown in the left column. Insets show higher (3.5x) magnification of the areas indicated in the main images. Scale bar, 5μm. (B) Quantification of the proportion of BACE1 that co-localized with hAPP after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % BACE co-localized with hAPP. N=3 independent experiments, each performed in duplicate; **, P<0.01 vs. WT (one-way ANOVA followed by post hoc test). (C) Quantification of the proportion of internalized hAPP that co-localized with BACE1 after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % internalized hAPP co-localized with BACE1. N=3 independent experiments, each performed in duplicate; *, P<0.05; **, P<0.01 vs. WT (one-way ANOVA followed by post hoc test).",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "(D) Micrographs of p75NTR after 15min internalization (red), Rab11 immunocytochemistry (green) and their superimposition in wild type hippocampal neurons. DAPI and MAP2 staining are shown in the left column. Insets show higher (3.5x) magnification of the areas indicated in the main merged images. Scale bar, 5μm. (E) Quantification of the proportion of Rab11 that co-localized with p75NTR after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % Rab11 co-localized with p75NTR. n=4; *, P<0.05; **, P<0.01 vs. WT (one-way ANOVA followed by post hoc test). (F) Quantification of the proportion of internalized p75NTR that co-localized with Rab11 after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % internalized p75NTR co-localized with Rab11. n=4; **, P<0.01 vs. WT (one-way ANOVA followed by post hoc test). ",
    "ncbi_link": "p75NTR: 18053"
  },
  {
    "caption": "(G) Micrographs of triple mutant hAPP after 15min internalization (red), Rab11 immunocytochemistry (green) and their superimposition in wild type hippocampal neurons infected with 5xFAD hAPP lentivirus. DAPI and MAP2 staining are shown in the left column. Insets show higher (3.5x) magnification of the areas indicated in the main merged images. Scale bar, 5μm. (H) Quantification of the proportion of Rab11 that co-localized with hAPP after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % Rab11 co-localized with hAPP. n=4; *, P<0.05 vs. WT (one-way ANOVA followed by post hoc test). (I) Quantification of the proportion of internalized hAPP that co-localized with Rab11 after 6 and 15 min of internalization at 37°C. Results are expressed as mean ± SEM of % internalized hAPP co-localized with Rab11. n=4; *, P<0.05 vs. WT (one-way ANOVA followed by post hoc test). ",
    "ncbi_link": "hAPP: 351"
  },
  {
    "caption": "(a) Intracellular ROS production was assessed using DCFH-DA. (b) Plasma membrane calcium influx was measured by analysing the quench of Fura-2 fluorescence upon addition of extracellular Mn2+. (a,b) Were conducted in enzymatically digested single FDBs from WT, mdx and p47−/−-mdx mice. Bars represent average±s.e.m. from n=15 individual fibres for each condition.",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "(d) Autophagy marker proteins were analysed by immunoblotting with antibodies as indicated (c) and (d) were conducted in enzymatically isolated fibres from FDBs of WT, mdx and p47−/−-mdx mice. Representative images are shown. GAPDH was detected as a loading control. Bars represent average±s.e.m. from n=3 independent biological experiments.",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "(e) LC3-LAMP1 colocalization in single FDBs from mdx and p47−/−-mdx mice was analysed using confocal microscopy. Representative images from n=3 independent biological experiments are shown (scale bar=100 and 40 μm for red box areas).",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "f) Immunofluorescence assay to detect lysosomes (LAMP1) in TA muscle from WT, mdx and p47−/−-mdx mice. White arrows indicate lysosome and yellow arrows indicate nucleus.",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "(g) Immunohistochemistry to detect lysosome (LAMP1) in TA muscle from WT, mdx and p47−/−-mdx mice. Black arrows indicate LAMP1 positive (brown) structures. Histogram plot quantifying the number of immunopositive LAMP1 structures per fibre. Representative images from n=3 independent biological experiments are shown. Scale bar represents 100 μm for f and 140 μm for g. Statistical differences between groups were determined using ANOVA with Tukey's post hoc test. *P0.05 and **P0.01.",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "(d) Serum creatine kinase activity. (e) Force-frequency relationship in Dia muscle strips from WT (black), mdx (red) and p47−/−-mdx (blue) mice. Scale bars represent 55 μm. For e, #P0.01 p47−/−-mdx versus mdx.##P0.01 p47−/−-mdx versus WT and mdx. Mdx was statistically different than WT at all frequencies of stimulation. Statistical differences between groups were determined using ANOVA with Tukey's post hoc test. *P0.05 and **P0.01.",
    "ncbi_link": "mdx: 13405
p47: 17969"
  },
  {
    "caption": "(G,H) dcr‐1 young adults have an increased number of seam cells (shown in brackets) and gaps in the alae (between arrows).",
    "ncbi_link": "dcr‐1: 176138"
  },
  {
    "caption": "(I,J) atg‐2 mutations suppress the retarded heterochronic defect in dcr‐1mutants. Complete alae (arrow) are formed in dcr‐1; atg‐2 double mutants.",
    "ncbi_link": "atg‐2: 180949
dcr‐1: 176138"
  },
  {
    "caption": "K-M Confocal images showing expression of hbl‐1::gfp::hbl‐1 reporter in VNC in wild type (K), atg‐2 (L) and epg‐6 (M) L3 larvae.",
    "ncbi_link": "atg‐2: 180949
epg‐6: 189705"
  },
  {
    "caption": "O-Q Confocal images showing the expression of the col‐10::gfp::lin‐41(3′UTR) reporter in wild type (O), atg‐2 (P) and atg‐3 (Q) late L4 larvae.",
    "ncbi_link": "atg‐2: 180949
atg‐3: 176921"
  },
  {
    "caption": "S,T Distribution of relative fluorescence intensity of hbl‐1::gfp in VNC and col‐10::gfp::lin‐41(3′UTR) in hypodermal cells in 50 unit areas in wild type, let‐363(RNAi) or starvation‐treated animals. Black lines in (N,R-T) represent the average fluorescence intensity of the reporter in each strain. P values are determined by Student's two‐tailed unpaired t‐test in (N,R-T). (C,E,G,I) Scale bar, 20 μm; (D,F,H,J-M,O-Q) scale bar, 10  μm. GFP, green fluorescent protein; miRISC, miRNA‐induced silencing complex; RNAi, RNA‐mediated interference; UTR, untranslated region; VNC, ventral nerve cord.",
    "ncbi_link": "let‐363: 172167"
  },
  {
    "caption": "A-C Wild‐type and atg‐2 hermaphrodites have a single vulva (arrow). (B) let‐60(n1046gf) mutants show a Muv phenotype. Black arrows indicate pseudovulvae.",
    "ncbi_link": "atg‐2: 180949
let‐60: 178104"
  },
  {
    "caption": "D Loss of autophagy activity suppresses the Muv phenotype in let‐60(n1046) mutants. The number of adult animals examined was: wild type (n=450), let‐60 (n=406), epg‐6; let‐60 (n=444), let‐60; atg‐2 (n=803), epg‐5; let‐60 (n=672), epg‐5; let‐60; ain‐1(ku322) (n=635). P values are determined by a two‐tailed χ2 test.",
    "ncbi_link": "ain‐1: 181719
atg‐2: 180949
epg‐5: 3565794
epg‐6: 189705
let‐60: 178104"
  },
  {
    "caption": "E,F lsy‐6 mutants show defects in ASEL fate specification and do not express the ASEL‐specific reporter lim‐6pro::GFP.",
    "ncbi_link": "lsy‐6: "
  },
  {
    "caption": "G Expression of lim‐6pro::GFP in various strains. aCompared with lsy‐6(ot150).bCompared with lsy‐6(ot150); ain‐1(ku322). P values are determined by a two‐tailed χ2 test.",
    "ncbi_link": "lsy‐6: 
ain‐1: 181719"
  },
  {
    "caption": "AIN‐1::GFP is weakly and diffusely expressed in the cytoplasm during embryogenesis in wild‐type animals. (A) Nomarski image of the embryo shown in (B). Scale bar, 10 μm for whole embryo. C. elegans embryos remain the same size during embryogenesis and loss of autophagy activity has no effect on the embryo size. Thus, scale bars for embryos are only shown once in each figure. (C) AIN‐1::GFP forms a large number of aggregates in epg‐6 mutant embryos. (A-C) are confocal images.",
    "ncbi_link": "epg‐6: 189705"
  },
  {
    "caption": "(E) No AIN‐1::GFP aggregates are formed in sqst‐1 mutant embryos.",
    "ncbi_link": "sqst‐1: 178139"
  },
  {
    "caption": "(F) AIN‐1::GFP accumulates into numerous aggregates in epg‐7 mutant embryos.",
    "ncbi_link": "epg‐7: "
  },
  {
    "caption": "(K) ALG‐2::GFP forms a few aggregates in epg‐6 mutant embryos. (L) ALG‐2::GFP forms a large number of aggregates in epg‐6 mutant embryos under stress conditions. GFP, green fluorescent protein; s.d., standard deviation.",
    "ncbi_link": "epg‐6: 189705"
  },
  {
    "caption": "(E-H) AIN‐1::GFP aggregates colocalize with SQST‐1 aggregates in atg‐3 mutant embryos. Scale bars, 10 μm for insets that show a magnified view.",
    "ncbi_link": "atg‐3: 176921"
  },
  {
    "caption": "(I-L) AIN‐1::GFP aggregates are separable from PGL granules, detected by anti‐SEPA‐1, in atg‐3 mutant embryos.",
    "ncbi_link": "atg‐3: 176921"
  },
  {
    "caption": "(M-P) Colocalization of AIN‐1::GFP aggregates with LGG‐1 puncta in epg‐6 mutant embryos.",
    "ncbi_link": "epg‐6: 189705"
  },
  {
    "caption": "(B) Mitochondria from CCCP‐treated or MPPβ knockdown cells were incubated ±0.1 M Na2CO3 before supernatant (S) and pellet (P) were separated by centrifugation. CCCP, carbonyl cyanide m‐chlorophenyl hydrazone; MPP, mitochondrial processing peptidase; NT, non‐targeting; PARL, presenilin‐associated rhomboid‐like protease; PINK1, phosphatase and tensin homologue‐induced kinase 1; siRNA, short interfering RNA; WB, western blot.",
    "ncbi_link": "MPPβ: 9512"
  },
  {
    "caption": "(A) Live confocal micrographs of siRNA‐, GFP‐Parkin‐ and OCT‐DsRed‐transfected HEK293T cells ±CCCP; Scale bars, 20 μm (low magnification) and 5 μm (high magnification).",
    "ncbi_link": "Parkin: 5071
OCT: 5362"
  },
  {
    "caption": "A, C & E, Confocal images of neuronal processes of fixed neurons transfected with MtDsRed and SYN-GFP and C, myc-Miro1 (Miro OE) or E, myc-Miro1ΔEF (Miro ΔEF). Neurons are either non-treated (NT), TTX treated (1 M, 48h), PTX treated (100 M, 48h), or DMSO treated (1:2000, as PTX). Scale bar, 10 m. B, D & F, Fraction of SYN-GFP clusters co-localising with mitochondria in cultures in B, control conditions, DMSO 28.7% 3.9, TTX 16.6% 3.1, PTX 50.0% 7.2, ANOVA **p<0.001, n=8-9 neurons, D, with the expression of myc-Miro1, DMSO 33.9% 4.7, TTX 35.9% 5.4, PTX 46.7% 4.0, ANOVA, *p<0.05, n=8-9, F, with the expression of myc-Miro1ΔEF, ANOVA p>0.05, n=9-12. Experiments performed in E16 mouse hippocampal neuronal cultures at DIV 10-12. Error bars represent SEM.",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "A, Live images of neurons co-transfected with SyGCaMP5 and MtDsRed or myc-ΔEF-Miro1-IRES-MtDsRed (ΔEF Miro) before and during 10 Hz field stimulation with and without TTX treatments. Scale bar, 10 m. B, Average ΔF/F0 SyGCaMP5 traces from terminals treated with TTX (red trace, ΔF/F0 = 2.5 0.5), n=10 neurons (62 terminals) and non-treated terminals (black trace, ΔF/F0 = 1.3 0.6), n=11 neurons (69 terminals) co-transfected with MtDsRed, *p<0.05, t-test. C, Average ΔF/F0 SyGCaMP5 traces from terminals treated with TTX (red trace, ΔF/F0 = 1.8 0.3) in n=7 neurons (33 terminals) and non-treated terminals (black trace, ΔF/F0 = 2.3 0.6) in n=7 neurons (32 terminals) co-transfected with myc-ΔEF-Miro1-IRES-MtDsRed; p=0.5, t-test. Experiments performed in E16 mouse hippocampal neuronal cultures at DIV 10-12. Error bars represent SEM.",
    "ncbi_link": "Miro1: 59040"
  },
  {
    "caption": "B The expression of mature miR-200b and miR-200a in the MOE of the NC and miR-200b/a KD mice, as revealed by qPCR analysis (n=4 mice each group; data represent the mean±SEM; *p<0.05, **p<0.01; Student's t-test).",
    "ncbi_link": "miR-200a: 387242
miR-200b: 387243"
  },
  {
    "caption": "C The expression of Ttll10 (the host gene of miR-200b/a) mRNA in the MOE of the NC and miR-200b/a KD mice, as revealed by qPCR analysis (n=4 mice each group; data represent the mean±SEM; p=0.3540; Student's t-test).",
    "ncbi_link": "miR-200b: 387243
Ttll10: 330010"
  },
  {
    "caption": "D The locomotor activity of the miR-200b/a KD mice was similar to that of the NC mice (NC: n=13 mice, miR-200b/a knockdown: n=15 mice; data represent the mean±SEM; p=0.5030; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "E The odorant habituation results shown as the ratio of odor sniffs/water of the miR-200b/a KD mice were significantly reduced compared to those of the NC mice. These odorants included male urine (1:50), female urine (1:50), isopentyl acetate (50 μM), citral (50 μM), 2-heptanone (50 μM) and propyl propionate (50 μM) (n=6 mice each group; data represent the mean±SEM; *p<0.05, **p<0.01, ***p<0.001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "The resident/intruder experiment showed that the attack frequency (F) of the miR-200b/a KD mice were impaired compared to those of the NC mice (NC: n=11 mice, miR-200b/a KD: n=10 mice; data represent the mean±SEM; ****p<0.0001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "G The resident/intruder experiment showed that the attack duration (G) of the miR-200b/a KD mice were impaired compared to those of the NC mice (NC: n=11 mice, miR-200b/a KD: n=10 mice; data represent the mean±SEM; ****p<0.0001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "H, I The analysis of male-female mating behaviors showed that the mating frequency (H) and duration (I) of the miR-200b/a KD mice were significantly reduced compared to those of the NC mice (NC: n=11 mice, miR-200b/a KD: n=10 mice; data represent the mean±SEM; **p<0.01, ***p<0.001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "B Representative IF staining with Ki67 antibody in the MOE of the NC and miR-200b/a KD mice. Scale bars, 20 μm. C Quantification of the numbers of Ki67+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; **p<0.01, ****p<0.0001; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "D Representative IF costaining with both EdU and Ki67 antibody in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the EdU+ cells and the yellow arrows indicate the cells positive for both EdU and Ki67. D' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (middle and right images). D: Scale bars, 20 μm; D': Scale bars, 2 μm. E Quantification of the numbers of costained Ki67+ and EdU+ cells in the MOE of the NC and miR-200b/a KD mice (n=3 mice each group; data represent the mean±SEM; *p<0.05; Student's t-test). F The proportion of GBCs that exited the cell cycle was significantly reduced in the miR-200b/a KD mice compared with their NC controls [the cell cycle exit index was calculated using the following formula: (EdU+ Ki67− cells/total EdU+ cells)×100; n=3 mice each group; data represent the mean±SEM; **p<0.01; Student's t-test]. ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "G Representative IF costaining with both EdU and BrdU antibody in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the BrdU+ cells, and the yellow arrows indicate the cells positive for both BrdU and EdU. G' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (middle and right images). G: Scale bars, 20 μm; G': Scale bars, 2 μm.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "H The S phase length of the GBCs in the MOE of the NC and miR-200b/a KD mice (the S phase length was calculated using the following formula: 3 h×BrdU+/BrdU+EdU-; n=3 mice each group; data represent the mean±SEM; *p<0.05; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "I Total cell cycle length of the GBCs in the MOE of the NC and miR-200b/a KD mice (total cell cycle length was calculated using the following formula: 20 h+(Ts×EdU+BrdU-/Edu+); n=3 mice each group; p=0.9785; data represent the mean±SEM; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "B The mRNA levels of CK14, Trp63, Sox2 and Mash1 in the MOE of the NC and miR-200b/a KD mice, as revealed by qPCR analysis (n=4 mice each group; data represent the mean±SEM; CK14: p=0.2135, Trp63: p=0.1930, Sox2: p=0.5190, *p<0.05; Student's t-test).",
    "ncbi_link": "Mash1: 17172
CK14: 16664
miR-200b: 387243
Sox2: 20674
Trp63: 22061"
  },
  {
    "caption": "C Representative IF staining for CK14, Sox2, and Mash1 in the MOE of the NC and miR-200b/a KD mice. Scale bars, 20 μm. D Quantification of the number of CK14+, basal Sox2+, apical Sox2+, and Mash1+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; CK14: p=0.8998, basal Sox2: p=0.7056, apical Sox2: p=0.4455, **p<0.01; Student's t-test). E Western Blot analysis of the Sox2 and Mash1 protein levels in the MOE of the NC and miR-200b/a KD mice (n=2 mice each group). GAPDH and Tubulin served as loading controls. The molecular weight of each band is indicated at the right. ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "F Representative IF costaining with Sox2 antibody and EdU in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the cells positive for both Sox2 and EdU. F' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (right images). F: Scale bars, 20 μm; F': Scale bars, 2 μm. G Quantification of the number of Sox2+EdU+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; p=0.7988; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "H Representative IF costaining with Mash1 antibody and EdU in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the cells positive for both Mash1 and EdU. H' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (right images). H: Scale bars, 20 μm; H': Scale bars, 2 μm. I Quantification of the number of Mash1+EdU+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; *p<0.05; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "A Representative IF staining for Tuj1, GAP43, and OMP in the MOE of the NC and miR-200b/a KD mice. Scale bars, 20 μm. B Quantification of the number of Tuj1+, GAP43+, and OMP+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; *p<0.05, **p<0.01, ***p<0.001; Student's t-test). C The mRNA levels of Ngn1, GAP43 and OMP in the MOE of the NC and miR-200b/a KD mice, as revealed by qPCR analysis (n=4 mice each group; data represent the mean±SEM; *p<0.05; Student's t-test). ",
    "ncbi_link": "GAP43: 14432
miR-200b: 387243
Ngn1: 18014
OMP: 18378"
  },
  {
    "caption": "D Representative IF costaining with GAP43 and BrdU antibodies in the MOE of the NC and miR-200b/a KD mice injected with BrdU at 3 d. The white arrows indicate the cells positive for both GAP43 and BrdU. D' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (middle and right images). D: Scale bars, 20 μm; D': Scale bars, 2 μm. E Quantification of the ratio of the number of BrdU+ GAP43+ cells and the number of total GAP43+ cells in the MOE of the NC and miR-200b/a KD mice injected with BrdU at 3 d (n=3 mice each group; data represent the mean±SEM; ****p<0.0001; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "F Representative IF staining with Cas3 antibody in the MOE of the NC and miR-200b/a KD mice. Scale bars, 20 μm. G Quantification of the number of Cas3+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; ***p<0.001; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "A The number of differentially expressed olfrs from RNA sequencing in the MOE of the NC and miR-200b/a KD mice.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "C TET 3' UTR-dependent expression of a luciferase reporter gene was suppressed by miR-200a overexpression. Luciferase reporter gene under the control of the wild-type (WT) or mutant (Mut) TET3 3' UTR was transfected along with the negative control (nc) RNA or miR-200a mimic duplexes into HeLa cells (n=6 from six independent experiments; data represent the mean±SEM; Mut-nc vs. Mut-mimic: p=0.3697, *p<0.05; Student's t-test).",
    "ncbi_link": "luciferase: 
Luciferase: 
miR-200a: 406983
TET: 194388
TET3: 194388"
  },
  {
    "caption": "D, E The expression of mature miR-200a (D) and TET3 (E) mRNA in the 3T3-L1 cells treated with miR-200a inhibitor, miR-200a mimic or control, as revealed by qPCR analysis (n=4 from four independent experiments; data represent the mean±SEM; D: F=66.37, E: F=16.39, NC vs. mimic: p=0.2597, *p<0.05, ***p<0.001; one-way ANOVA and Bonferroni pairwise comparisons).",
    "ncbi_link": "miR-200a: 387242
TET3: 194388"
  },
  {
    "caption": "F Western Blot analysis of the TET3 protein level in the 3T3-L1 cells treated with miR-200a inhibitor, miR-200a mimic or control (n=3 from three independent experiments). Actin served as a loading control. The molecular weight of each band is indicated at the right.",
    "ncbi_link": "miR-200a: 387242"
  },
  {
    "caption": "Western Blot analysis of the TET3 protein level in the MOE of the mice intranasally injected with miR-200a (G) NC mimic (n=3 mice each group). Actin served as a loading control. The molecular weight of each band is indicated at the right.",
    "ncbi_link": "miR-200a: 387242"
  },
  {
    "caption": "H Western Blot analysis of the TET3 protein level in the MOE of the mice intranasally injected with miR-200b (H) or NC mimic (n=3 mice each group). Actin served as a loading control. The molecular weight of each band is indicated at the right.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "I Western Blot analysis of the TET3 protein level in the MOE of the NC and miR-200b/a KD mice (n=3 mice each group). Actin served as a loading control. The molecular weight of each band is indicated at the right. The blue number shows the ratio of the average intensity of TET3/Actin.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "J Representative IF staining of TET3 in the MOE of the NC and miR-200b/a KD mice. Scale bars: 20 μm.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "K Quantification of the number of TET3+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; ***p<0.001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "L Representative IF staining of 5mC in the MOE of the NC and miR-200b/a knockdown mice. L' is shown at higher magnification of the boxed region. L: Scale bars, 20 μm; L': Scale bars, 2 μm.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "M Quantification of the number of 5mC+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; ***p<0.001; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "N Representative IF staining of 5hmC in the MOE of the NC and miR-200b/a knockdown mice. N' is shown at higher magnification of the boxed region. N: Scale bars, 20 μm; N': Scale bars, 2 μm.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "Quantification of the number of 5hmC+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; **p<0.01; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "A Representative IF staining for costaining with TET3 and Mash1 antibodies in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the cells positive for both TET3 and Mash1. A' is shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (middle and right images). A: Scale bars, 20 μm; A': Scale bars, 2 μm. B Quantification of the number of costained TET3+ and Mash1+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; ***p<0.001; Student's t-test). ",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "C, D The resident/intruder experiment showed that the attack frequency (C) and duration (D) of the miR-200b/a+TET3 DKD mice were significantly improved compared with those of the miR-200b/a KD controls; [200 KD: miR-200b/a KD; (200+T) DKD: (miR-200b/a+TET3) DKD; (NC: n=18 mice, miR-200b/a KD: n=14 mice, miR-200b/a+TET3 DKD: n=16 mice; data represent the mean±SEM; C: F=17.84, D: F=12.06, *p<0.05, ***p<0.001, ****p<0.0001; One-way ANOVA and Bonferroni pairwise comparisons)].",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "E, F The analysis of male-female mating behaviors showed that the frequency (E) and duration (F) of mating to females of the miR-200b/a+TET3 DKD mice were significantly reduced compared with those of their NC controls and were not dramatically different compared with those of the miR-200b/a KD mice (NC: n=18 mice, miR-200b/a KD: n=14 mice, miR-200b/a+TET3 DKD: n=16 mice; data represent the mean ±SEM; E: F=15.62, F: F=15.56, ***p<0.001, ****p<0.0001; one-way ANOVA and Bonferroni pairwise comparisons).",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "G Representative IF staining for Mash1, Tuj1, Cas3 and Ki67 in the MOE of the NC, miR-200b/a KD, and miR-200b/a+TET3 DKD mice. Scale bars: 20 μm. H-K Quantification of the numbers of Mash1+(H), Tuj1+(I), Cas3+(J) and Ki67+(K) cells in the MOE of the NC, miR-200b/a KD, and miR-200b/a+TET3 DKD mice (n=4 mice each group; data represent the mean±SEM; Mash1: F=41.45, Tuj1: F=113.9, Cas3: F=92.51, Ki67: F=61.35, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001; one-way ANOVA and Bonferroni pairwise comparisons). ",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "A The REST mRNA expression in the MOE of the NC, miR-200b/a KD and miR-200b/a+TET3 DKD mice, as revealed by qPCR analysis [200 KD: miR-200b/a KD; (200+T) DKD: (miR-200b/a+TET3) DKD; n=4 mice each group; data represent the mean±SEM; F=9.409, NC vs. 200: p=0.1367, 200 vs. 200+T: p=0.1896, **p<0.01; one-way ANOVA and Bonferroni pairwise comparisons",
    "ncbi_link": "miR-200b: 387243
REST: 19712
TET3: 194388"
  },
  {
    "caption": "B Western Blot analysis of the REST protein level in the MOE of the NC, miR-200b/a KD and miR-200b/a+TET3 DKD mice (n=3 mice each group). Actin served as a loading control.",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "C Representative IF staining for REST in the MOE of the NC, miR-200b/a KD, and miR-200b/a and TET3 DKD mice. Scale bars: 20 μm.",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "D Quantification of the number of REST+ cells in the MOE of the NC, miR-200b/a KD, and miR-200b/a+TET3 DKD mice (n=4 mice each group; data represent the mean±SEM; F=12.11, *p<0.05; one-way ANOVA and Bonferroni pairwise comparisons).",
    "ncbi_link": "miR-200b: 387243
TET3: 194388"
  },
  {
    "caption": "Representative IF costaining with REST and Mash1 antibodies in the MOE of the NC and miR-200b/a KD mice. The white arrows indicate the cells positive for both REST and Mash1. E' are shown at higher magnification of the boxed region, as three channel merged images (left image) and the separated channel (middle and right images). E: Scale bars, 20 μm; E': Scale bars, 2 μm.",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "F Quantification of the number of costained REST+ and Mash1+ cells in the MOE of the NC and miR-200b/a KD mice (n=4 mice each group; data represent the mean±SEM; **p<0.01; Student's t-test).",
    "ncbi_link": "miR-200b: 387243"
  },
  {
    "caption": "A, B The resident/intruder experiment showed that the attack frequency (A) and duration (B) of the miR-200b/a+REST DKD mice were dramatically improved compared with those of the miR-200b/a KD mice [200 KD: miR-200b/a KD; (200+R) DKD: (miR-200b/a+REST) DKD; NC: n=10 mice, miR-200b/a KD: n=9 mice, miR-200b/a+REST DKD: n=13 mice; data represent the mean±SEM; A: F=10.62, B: F=10.54, ***p<0.001; one-way ANOVA and Bonferroni pairwise comparisons].",
    "ncbi_link": "miR-200b: 387243
REST: 19712"
  },
  {
    "caption": "C, D The analysis of male-female mating behaviors showed that the frequency (C) and duration (D) of mating to females of the miR-200b/a+REST DKD mice were significantly improved compared with those of the miR-200b/a KD mice (NC: n=10 mice, miR-200b/a KD: n=9 mice, miR-200b/a+REST DKD: n=13 mice; data represent the mean±SEM; C: F=6.162, D: F=6.360, *p<0.05, **p<0.01; one-way ANOVA and Bonferroni pairwise comparisons).",
    "ncbi_link": "miR-200b: 387243
REST: 19712"
  },
  {
    "caption": "Representative IF staining for Mash1, Tuj1, Cas3 and Ki67 in the MOE of the NC, miR-200b/a KD, and miR-200b/a+REST DKD mice. Scale bars: 20 μm. F-I Quantification of the number of Mash1+(F), Tuj1+(G), Cas3+(H) and Ki67+(I) cells in the MOE of the NC, miR-200b/a KD, and miR-200b/a+REST DKD mice (n=4 mice each group; data represent the mean±SEM; Mash1: F=35.53, Tuj1: F=62.28, Cas3: F=115.7, Ki67: F=77.43, **p<0.01, ***p<0.001, ****p<0.0001; one-way ANOVA and Bonferroni pairwise comparisons). ",
    "ncbi_link": "miR-200b: 387243
REST: 19712"
  },
  {
    "caption": "B. Blue native-PAGE loading of protein extracts from nrc2/3/4 knockout N. benthamiana plants after immunoprecipitation with anti-Flag antibody. Co-migration of Rpi-amr3-HF and AVRamr3-V5 are indicated (*, red). Same samples were loaded twice on one blue native-PAGE gel, transferred onto one membrane, and then the membrane was cut into two and immunoblotted separately. GUS-V5, β-glucuronidase fused with V5 tag. C. NRC2EEE-Myc does not alter association between Rpi-amr3 and AVRamr3. Samples of Fig 1B were SDS-boiled and loaded on SDS-PAGE. Input samples were taken prior to immunoprecipitation to show expression of all proteins.",
    "ncbi_link": "GUS: 
nrc2: "
  },
  {
    "caption": "B. NRC2EEE and Rpi-amr3 migration in the absence of effector. N. benthamiana nrc2/3/4 knockout plants were transiently infiltrated with Rpi-amr3-HF, NRC2EEE-Myc and GUS-V5 followed by 2D-PAGE. NRC2EEE-Myc proteins (*, red) and Rpi-amr3-HF proteins (*, blue) is indicated. C. NRC2EEE and Rpi-amr3 migration in the presence of effector. N. benthamiana nrc2/3/4 knockout plants were transiently infiltrated with Rpi-amr3-HF, NRC2EEE-Myc and AVRamr3 -V5 followed by 2D-PAGE. NRC2EEE-Myc proteins (*, red) and Rpi-amr3-HF protein (*, blue) is indicated.",
    "ncbi_link": "nrc2: "
  },
  {
    "caption": "D. Re-localization of NRC2EEE-Myc upon effector-dependent activation of Rpi-amr1. Lysates of nrc2/3/4 knockout plants transiently expressing Rpi-amr1-Flag, NRC2EEE-Myc with AVRamr3-V5 or AVRamr1-V5 were fractionated into total (T), soluble (S), and pellet (P) fractions. E. Re-localization of NRC2EEE-Myc upon effector-dependent activation of Rpi-amr3. Lysates of nrc2/3/4 knockout plants transiently expressing Rpi-amr3-HF, NRC2EEE-Myc with AVRamr3-V5 or AVRamr1-V5 were fractionated into total (T), soluble (S), and pellet (P) fractions.",
    "ncbi_link": "nrc2: "
  },
  {
    "caption": "A. P-loop of Rpi-amr3 is required for AVRamr3-dependent HR in N. benthamiana. Representative leaf phenotype of HR (hypersensitive response) in wild-type N. benthamiana is shown. The number of leaves tested and occurrences of HR are indicated in parentheses. B. P-loop of NRC2 is required for AVRamr3-dependent HR in N. benthamiana nrc2/3/4 knockout plants. Representative leaf phenotype of HR is shown. The number of leaves tested and occurrences of HR are indicated in parentheses.",
    "ncbi_link": "AVRamr3: 
NRC2: 
nrc2: 
Rpi-amr3: "
  },
  {
    "caption": "B. Protein lysates expressing NRC4AAA-Myc with Rpi-amr3-HF or Rpi-amr1-Flag in the presence and absence of cognate effector were loaded on blue native-PAGE. Proteins were transiently expressed in N. benthamiana nrc2/3/4 knockout plants. Non-specific bands are indicated with *.",
    "ncbi_link": "nrc2: "
  },
  {
    "caption": "B. NRC2EEE-Myc oligomerizes in response-dependent manner. Protein lysates from N. benthamiana nrc2/3/4 knockout transiently expressing NRC2EEE-Myc, Rpi-amr3-HF and AVRamr3 alleles from P. infestans, P. capsici, and P. parasitica were loaded on blue native-PAGE and blotted for NRC2EEE (anti-Myc). C. Recognition is correlated with interaction and protein complex formation of AVRamr3 with Rpi-amr3. Protein extracts from Fig 5B were immunoprecipitated with anti-Flag antibody, separated on blue native-PAGE, and AVRamr3-GFP proteins of P. infestans, P. capsici, and P. parasitica were visualized.",
    "ncbi_link": "HF: 
Myc: 
NRC2: 
nrc2: 
Rpi-amr3: "
  },
  {
    "caption": "A. Representative spinning disk confocal live-cell imaging time series of U2OS cells stably co-expressing PA-GFP-α-tubulin (cyan) and mCherry-α-tubulin (red), treated with control and KIF4A siRNAs. White arrowheads highlight poleward motion of the photoactivated regions due to MT-flux. Scale bars, 10 µm. Time, min:sec.",
    "ncbi_link": "KIF4A: 24137"
  },
  {
    "caption": "Quantification of MT-flux in bipolar spindles subjected to indicated treatments. Graphs represent MT flux of individual cells with mean ± SD. N (number of cells, number of independent experiments): - bipolar spindles: siControl (49, 5), STLC (31, 3), siKIF15 (39, 3), siKID (32, 3), siKIF4A (28, 3), siKIF2A (36, 3), siCLASPs (21, 2), GSK923295 (44, 3)",
    "ncbi_link": "KID: 363
CLASPs: 23122///23332
KIF15: 56992
KIF2A: 3796
KIF4A: 24137"
  },
  {
    "caption": "Quantification of MT-flux in monopolar spindles subjected to indicated treatments. Graphs represent MT flux of individual cells with mean ± SD. N (number of cells, number of independent experiments) monopolar spindles: siControl (35, 3), siKIF15 (44, 3), siKID (38, 3), siKIF4A (44, 3), siKIF2A (38, 3), siCLASPs (12, 2), GSK923295 (33, 3).",
    "ncbi_link": "KID: 363
CLASPs: 23332///23122
KIF15: 56992
KIF2A: 3796
KIF4A: 24137"
  },
  {
    "caption": "A. Representative spinning disk confocal live-cell imaging time series images of U2OS PA-GFP-α-tubulin cells conditionally co-expressing KIF4A shRNA and RNAi-resistant mCherry-Kif4A variants induced using doxycycline. Chromosomes were stained using SiR-DNA. White arrowheads highlight poleward flux of the photoactivated regions. Scale bar, 10 µm. Time, min:sec.",
    "ncbi_link": "mCherry: 
KIF4A: 24137
Kif4A: 24137"
  },
  {
    "caption": "B. Representative immunoblot of cell lysates obtained before and after doxycycline induction to validate the efficiency of KIF4A shRNA construct and expression of the RNAi-resistant mCherry-KIF4A variants. The anti-KIF4A antibody was used, together with anti-vinculin antibody as a loading control.",
    "ncbi_link": "mCherry: 
KIF4A: 24137"
  },
  {
    "caption": "C. Quantification of MT-flux upon shRNA-mediated depletion of KIF4A alone or in combination with conditional expression of the RNAi-resistant mCherry-KIF4A variants. The bars in graph represent mean ± SD. N (number of cells, number of independent experiments): uninduced shKIF4A (48, 4), shKIF4A (60, 4), uninduced KIF4A WT (36, 5), shKIF4A + KIF4A WT (43, 5), uninduced KIF4A K94A (42, 7), shKIF4A + KIF4A K94A (38, 6), uninduced KIF4A ΔZip1 (32, 4), shKIF4A + ΔZip1 (30, 4).",
    "ncbi_link": "mCherry: 
KIF4A: 24137"
  },
  {
    "caption": "B. Quantification of the impact of the MT-crosslinking proteins on MT-flux in U2OS PA-GFP/mCherry-α-tubulin cells transfected with respective siRNAs. Graph represent MT-flux values with mean ± SD. N (number of cells, number of independent experiments): siControl (49, 5), siPRC1 (45, 3), siNuMA (40, 3), siHSET (37, 3), siHSET + siNuMA (39, 3).",
    "ncbi_link": "HSET: 3833
NuMA: 4926
PRC1: 9055"
  },
  {
    "caption": "C. Quantification of the impact of the motor activity of HSET on MT-flux in U2OS cells stably expressing mEOS-α-tubulin treated with control or HSET 3′UTR siRNAs in presence or absence of the respective RNAi-resistant GFP-HSET constructs. Graph represent MT-flux values with mean ± SD. N (number of cells, number of independent experiments): siControl (23, 3), siHSET 3′UTR (33, 3), siHSET 3′UTR + HSET WT (29, 5), siHSET 3′UTR + HSET N593K (30, 4).",
    "ncbi_link": "GFP: 
mEOS: 
α-tubulin: 
HSET: 3833"
  },
  {
    "caption": "B. Quantification of the impact of stable end-on KT-MT attachments on MT-flux in NDC80-depleted cells under indicated conditions and in early prometaphase cells with and without the CENP-E inhibitor GSK923295. MT-flux values are plotted with mean ± SD. N (number of cells, number of independent experiments): siControl (49, 5), siNDC80 (59, 6), siNDC80 + siKIF4A (41, 3), siNDC80 + STLC (bipol.) (28, 3), siNDC80 + siKIF15 (36, 4), siNDC80 + siCLASPs (33, 3), siNDC80 + siKIF2A (38, 4), siNDC80 + GSK923295 (38, 3), early prometaphase (23, 3), early prometaphase + GSK923295 (28, 3).",
    "ncbi_link": "CLASPs: 23332///23122
KIF15: 56992
KIF2A: 3796
KIF4A: 24137
NDC80: 10403"
  },
  {
    "caption": "A. Representative maximum-intensity projected coherent-hybrid STED (CH-STED) images of mitotic spindles in U2OS cells treated with control and NDC80 siRNAs and stained for DNA (DAPI), KTs (CENP-C, magenta), α-tubulin (red) and CENP-E (green). Scale bar, 10 µm.",
    "ncbi_link": "NDC80: 10403"
  },
  {
    "caption": "B. Model illustrating potential mechanisms for CENP-E mediated MT-flux forces either through its KT- or antiparallel MT- based localization and sliding. CENP-E localized at KTs laterally interacting with MTs (white arrowheads in 1, 2), and CENP-E localized at interpolar MTs (white arrows in 3, 4), in control and NDC80-depleted mitotic cells. Scale bars, 2 µm.",
    "ncbi_link": "NDC80: 10403"
  },
  {
    "caption": "C. CH-STED analyses of HeLa cells stably expressing CENP-E-GFP illustrating bipolar spindles in prometaphase, metaphase and just after sister-chromatid separation at anaphase onset. Approximate x-y resolution is 70 nm. The expected/described localization of CENP-E-GFP (green) at KTs is shown. In addition, CENP-E-GFP was found associated with interpolar MTs (ipMTs), including regions of overlapping anti-parallel MTs, and k-fibers. Chromosomes (confocal mode only) were revealed in the larger panels with DAPI (cyan) and MTs (magenta) were detected with an anti-α-tubulin antibody. Arrows indicate examples of clear MT bundles, including regions of overlapping anti-parallel MTs. Scale bar in all panels is 5 μm.",
    "ncbi_link": "CENP-E: 
GFP: "
  },
  {
    "caption": "D. Representative spinning disk confocal live-cell time series of HeLa cells stably expressing CENP-E-GFP. White arrowheads highlight CENP-E-GFP at KTs, white arrows highlight CENP-E-GFP on interpolar MTs. Scale bar, 10 µm. Time, hour:min.",
    "ncbi_link": "CENP-E: 
GFP.: "
  },
  {
    "caption": "B, C. Quantification of MT-flux in prometaphase (B) and metaphase (C) bipolar spindles subjected to indicated treatments. Graphs represent MT flux of individual cells with mean ± SD. siNDC80, siNDC80 + GSK923295, early prometaphase, early prometaphase + GSK923295, siControl, and siKIF4A N (number of cells, number of independent experiments): siNDC80 + KIF15 + STLC (33, 5), siNDC80 + KIF15 + STLC + GSK923295 (25, 3), early prometaphase + KIF15 + STLC + GSK923295 (11, 2), siKIF15 + STLC (29, 3), siKIF4A + siKIF15 + STLC (10, 3).",
    "ncbi_link": "KIF15: 56992
KIF4A: 24137
NDC80: 10403"
  },
  {
    "caption": "A-C. Graph depicting a direct correlation between MT-flux and mitotic spindle where mean spindle length is plotted over mean MT-flux rates for all indicated conditions (A), mitotic conditions containing stable end-on attachments (B), and NDC80 depleted conditions lacking stable end-on attachments (C). Solid and dotted lines represent the linear regression and 95% confidence interval, respectively. Pearson correlation coefficient (r), coefficient of determination (r2) and corresponding p values are indicated. The error bars over x and y axis represent the standard deviation of MT-flux and spindle length, respectively.",
    "ncbi_link": "NDC80: 10403"
  },
  {
    "caption": "E. Quantification of spindle lengths at metaphase following indicated treatments. Graph represents the spindle length of individual cells with mean ± SD. N (number of cells, number of independent experiments): siControl (49, 5), siMCAK (34,3), siKIF4A + siKIF15 + STLC (46, 6), siKIF4A + siKIF15 + STLC + siMCAK (43, 3), siKIF4A + siKIF15 + STLC + siKIF2A (22, 3), siCLASPs (64, 6), siCLASPs + siMCAK (33, 3), siCLASPs + siKIF2A (32, 3).",
    "ncbi_link": "CLASPs: 23332///23122
CLASPs: 23122///23332
KIF15: 56992
KIF2A: 3796
MCAK: 11004
KIF4A: 24137"
  },
  {
    "caption": "Results of three independent microscopy-based screens in U2OS cells. Knockdown of Luciferase (blue) and the positive controls PPM1D and βTrCP (red) are indicated. A low/high Z-score indicates less/more phospho-histone H3 positive cells compared to the control, reflecting reduced/increased numbers of cells going into mitosis in the respective knockdowns after 5 Gy of IR. Deconvolution of the 41 primary hits in U2OS cells by four separate siRNA oligonucleotides. Grey represents a recovery value that is similar to the Luciferase control (<0.5 SD) and the red represents an altered recovery value (>0.5 SD) in two independent experiments.",
    "ncbi_link": "Luciferase: 
βTrCP: 8945
PPM1D: 8493"
  },
  {
    "caption": "RPE1 cells were depleted for p53 in combination with the indicated proteins by siRNA, in conditions used for the primary screen (2 Gy of IR). Mitotic entry was analyzed by MPM2 and PI staining by flow cytometry. For normalization see materials and methods. Error bars represent the SEM of three independent experiments.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "U2OS cells were transfected with four different siRNA oligonucleotides targeting PHF6, synchronized in G2 and subsequent recovery after 5 Gy of IR and the addition of nocodazole was analyzed by flow cytometry with MPM2 staining PPM1D and βTrCP were used as positive controls.",
    "ncbi_link": "βTrCP: 8945
PHF6: 84295
PPM1D: 8493"
  },
  {
    "caption": "U2OS cells were transfected with four different siRNA oligonucleotides targeting PHF6, synchronized in G2 or cells were lysed and analyzed using western blotting with the indicated antibodies",
    "ncbi_link": "PHF6: 84295"
  },
  {
    "caption": "U2OS WT, PHF6 knockout and PHF6 knock out cells that were reconstituted with GFP-PHF6 were synchronized in G2 and recovery was determined after 2 Gy of IR using flow cytometry with pHH3 staining",
    "ncbi_link": "GFP: 
PHF6: 84295"
  },
  {
    "caption": "U2OS WT, PHF6 knockout and PHF6 knock out cells that were reconstituted with GFP-PHF6 were synchronized in G2 cells were lysed and analyzed using western blotting with the indicated antibodies",
    "ncbi_link": "GFP: 
PHF6: 84295"
  },
  {
    "caption": "U2OS WT and PHF6 knockout cells were irradiated using 3 Gy of IR and cells were fixed at different time points for immunofluorescence. In (F) is presented 53BP1 IRIF intensity. In (G) is shown the number of γH2AX foci per cell.",
    "ncbi_link": "PHF6: 84295"
  },
  {
    "caption": "U2OS WT and PHF6 knockout cells were left untreated or irradiated with 3 Gy and processed after 1 h for comet assay analysis. The comet tail moment was analyzed in at least 50 individual cells.",
    "ncbi_link": "PHF6: 84295"
  },
  {
    "caption": "U2OS cells stably expressing GFP-PHF6 and mCherry-NBS1 were laser-irradiated and cells were analyzed by time-lapse imaging.",
    "ncbi_link": "GFP: 
mCherry: 
NBS1: 4683
PHF6: 84295"
  },
  {
    "caption": "U2OS cells stably expressing GFP-PHF6 were laser-irradiated and cells were analyzed by time-lapse imaging. In (B), the PARP inhibitor Olaparib was added 30 min before laser-induced damage. At least 60 cells were analyzed in three individual experiments and error bars represent the SD (lower panel). Scale bar is 5 μM.",
    "ncbi_link": "GFP: 
PHF6: 84295"
  },
  {
    "caption": "GC92 SV40 immortalized human fibroblasts containing the I-SceI NHEJ reporter were transfected with the indicated siRNA oligos and I-SceI. 48 h later the cells were fixed and analyzed by flow cytometry. Represented is the relative repair efficiency as compared to the Luciferase control.",
    "ncbi_link": "Luciferase: 
I-SceI: 854590"
  },
  {
    "caption": "Clonogenic survival assays of U2OS WT and PHF6 knockout cells that were depleted for luciferase or XRCC4 and treated with 2, 3 or 4 Gy IR. Shown is the relative survival as compared to the undamaged control. Error bars represent the SEM of three individual experiments.",
    "ncbi_link": "luciferase: 
PHF6: 84295
XRCC4: 7518"
  },
  {
    "caption": "GC92 SV40 immortalized human fibroblasts containing the I-SceI NHEJ reporter were transfected with the indicated siRNA oligos and I-SceI. 48 h later genomic DNA was extracted and repair of I-SceI cut-sites analyzed through junction analysis (n= independently derived sequences, see materials and methods for details).",
    "ncbi_link": "I-SceI: 854590"
  },
  {
    "caption": " (I) RT-qPCR of ZIKV RNA in infected hNSCs transfected with siRNAs targeting LC3, BECN or ATG9A 48 h post infection. Mean ± SEM of 3 biological replicates. *p < 0.05 by Student's t test. ",
    "ncbi_link": "ATG9A: 79065
BECN: 8678
LC3: 81631"
  },
  {
    "caption": "(C-D) RT-qPCR analysis of ZIKV mRNA 48 h after ZIKV infection of HeLa cells overexpressing FANCC (C) or FANCC-specific siRNA (D). Mean ± SEM of biological triplicates. **p < 0.01 by Student's t test.",
    "ncbi_link": "FANCC: 2176"
  },
  {
    "caption": "(E) Flow cytometry analysis of ZIKVE expression in mock-infected (red), ZIKV-infected (blue), ZIKV-infected siFANCC-transfected (orange), and ZIKV-infected siE2F4-transfected (green) hNSCs at 48 h post-infection.",
    "ncbi_link": "E2F4: 1874
FANCC: 2176"
  },
  {
    "caption": "(G) ZIKV NS1 expression 48 h after ZIKV infection of hNSCs expressing control siRNA (NTC) or siFANCC-targeting siRNA. Scale bar = 100 µm. (H-I) ZIKV NS1 expression 48 h after ZIKV infection of hNSCs expressing control (NTC) or siE2F4-targeting siRNA. Mean ± SEM of six imaging fields of biological triplicates, **p < 0.01 by Student's t test, Scale bar = 100 µm, ",
    "ncbi_link": "E2F4: 1874
FANCC: 2176"
  },
  {
    "caption": "(J) Immunoblot of macroautophagy (p62, LC3I/LC3II) and selective autophagy (FANCC, TOMM20) proteins 24 h after overexpression of FLAG-tagged ZIKV NS1, NS2B, NS3, NS4A, NS4B and NS5 in 293FT cells.",
    "ncbi_link": "FLAG: 
NS1: 7751225
NS2B: 7751225
NS3: 7751225
NS4A: 7751225
NS4B: 7751225
NS5: 7751225"
  },
  {
    "caption": "(L-M) Heatmaps of RT-qPCR analysis of FA pathway genes (K) or essential selective autophagy genes (L) in hNSCs 48 h after transfection with control (NTC) or E2F4-targeting siRNAs or after infection with ZIKV MR766 and Paraiba strains. Color patterns in heat map indicate as red showing the highest expression and blue showing the lowest expression of genes.",
    "ncbi_link": "E2F4: 1874"
  },
  {
    "caption": "(A) Representative images of mock- or ZIKV-infected human neurospheres expressing control (NTC) or FANCC-targeting siRNAs at 1-4 days post-infection. Scale bar = 250 µm. (B-C) Violin plot (B) and box plot (C) of relative size of neurospheres treated as described in (A) and measured on day 4 (B) or days 1-4 (C). Box plots show the mean and the smallest; largest values in whiskers represent the 10th and 90th percentiles in 50 randomly selected cells per group; and solid horizontal line indicates median. ***p < 0.001 by Student's t test. ",
    "ncbi_link": "FANCC: 2176"
  },
  {
    "caption": "Immunostaining of neural progenitor marker SOX2 (green) and ZIKV envelope flavivirus group antigen (ZIKVE, red) in the hippocampus of uninfected or ZIKV Paraiba-infected Ifnar-/- mice six days post-infection. Nuclei were stained with DAPI (gray). Right-most column in (A) shows enlargements of the regions. CC = cortical cortex, GCL = granular cell layer, LV = lateral ventricle, SGZ = subgranular zone, STR = striatum, SVZ = subventricular zone. Scale bars, 100 μm.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "Immunostaining of neural progenitor marker SOX2 (green) and ZIKV envelope flavivirus group antigen (ZIKVE, red) in the SVZ of uninfected or ZIKV Paraiba-infected Ifnar-/- mice six days post-infection. Nuclei were stained with DAPI (gray). Right-most column in (A) shows enlargements of the regions. CC = cortical cortex, GCL = granular cell layer, LV = lateral ventricle, SGZ = subgranular zone, STR = striatum, SVZ = subventricular zone. Scale bars, 100 μm.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "(C) RT-qPCR analysis of relative ZIKV RNA in different brain regions of Ifnar-/- mice. mean±SEM of n=3 biological replicates, **p<0.005, ***p<0.001 by Student's t test.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "(D) RT-qPCR analysis of relative Fancc mRNA levels from whole brains or testes in mock- and ZIKV Paraiba infected Ifnar-/- mice six days post-infection. Mean ± SEM of n=3 biological replicates, *p < 0.05 and ns by Student's t test.",
    "ncbi_link": "Fancc: 14088
Ifnar: 15975"
  },
  {
    "caption": "(E) RT-qPCR analysis of relative Fancc or Fancl mRNA levels from whole brains from mock- and ZIKV Paraiba infected Ifnar-/- newborn mice. Mean ± SEM of n=3 biological replicates, ***p < 0.001 by Student's t test.",
    "ncbi_link": "Fancc: 14088
Fancl: 67030
Ifnar: 15975"
  },
  {
    "caption": "(F) Western blot analysis of Fancc protein in brain regions from mock- and ZIKV Paraiba infected Ifnar-/- mice six days post-infection. HP = hippocampus, CT= cortex, ST = striatum and OB= Olfactory Bulb.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "(H) RT-qPCR analysis of relative ZIKV RNA in different brain regions of Fancc KO neonatal mice six days post-infection. mean±SEM of n=3 biological replicates, **p<0.005, ***p<0.001 by Student's t test.",
    "ncbi_link": "Fancc: 14088"
  },
  {
    "caption": "(I) qRT-PCR for Ifnab gene expression in wild type and Fancc KO mice, Mean ± SEM of n=3 biological replicates, ns by Student's t test.",
    "ncbi_link": "Fancc: 14088
Ifnab: 15974"
  },
  {
    "caption": "(A) Immunostaining of immature neuronal marker DCX (green) and ZIKV envelope (ZIKVE, red) in the hippocampus of uninfected or ZIKV Paraiba-infected Ifnar-/- mice six days post-infection. Nuclei were stained with DAPI (gray). Bottom row shows enlargements of the hippocampus region. GCL = granular cell layer, SGZ = subgranular zone, DG = dentate gyrus, InGr = internal granular layer, Me = medulla, OB = olfactory bulb. Scale bars, 50 and 100 μm.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "Immunostaining of immature neuronal marker DCX (green) and ZIKV envelope (ZIKVE, red) in the olfactory bulb of uninfected or ZIKV Paraiba-infected Ifnar-/- mice six days post-infection. Nuclei were stained with DAPI (gray). InGr = internal granular layer, Me = medulla, OB = olfactory bulb. Scale bars, 50 and 100 μm.",
    "ncbi_link": "Ifnar: 15975"
  },
  {
    "caption": "(C-E) Western blot of autophagy protein LC3 and p62 in different brain region of Fancc KO neonatal mice six days post-infection of ZIKV (MR766). Mean ± SEM of n=3 biological replicates, *p<0.05, **p<0.005, by Student's t test. HP = hippocampus, CT= cortex, ST = striatum and OB= Olfactory Bulb.",
    "ncbi_link": "Fancc: 14088"
  },
  {
    "caption": "(F) Representative immunofluorescent images showing immunoreactivity of neural progenitor marker (Sox2) with apoptosis marker (Cleaved-caspase-3, CC3) in hippocampus region of Fancc KO mice. Scale bar=50µm. (G) Quantitative analysis of number of Sox2+ cells and Sox2/CC3+ co-labelled cells in Fancc KO mice hippocampal brain region. Mean ± SEM, n=3 biological replicates, *p < 0.05 by Student's t test.  ",
    "ncbi_link": "Fancc: 14088"
  },
  {
    "caption": "A, B Nucleosome maps at and surrounding, the TSS region of the NANOG and GRIA1 genes in pl-iPSC (upper, black) and in NPC cells (lower, grey). The TSS is indicated by a dashed line at chr 12: 7,941,991 for NANOG and chr5: 152,870,105 for GRIA1. * indicates the position of a highly positioned nucleosome associated with the TSS of the active gene.",
    "ncbi_link": "GRIA1: 2890
NANOG: 79923"
  },
  {
    "caption": "(E-F) Serum levels of T (E) and LH (F) in WT males, ARLmon/Y and AR-/Y mice at the age of 13 weeks.",
    "ncbi_link": "AR: 11835"
  },
  {
    "caption": "(D) RT-qPCR analyses of Rhox5 and Insl3 of testes from 13-week old WT males, ARLmon/Y and AR-/Y. Expression levels are normalized to WT.",
    "ncbi_link": "AR: 11835
Insl3: 16336
Rhox5: 18617"
  },
  {
    "caption": "(B) Serum levels of A-dione in WT males, ARLmon/Y and AR-/Y mice at the age of 13 weeks.",
    "ncbi_link": "AR: 11835"
  },
  {
    "caption": "(D) Reporter gene assays in Hela cells co-transfected with the mouse Insl3 promotor together with the WT or mutant mouse AR.",
    "ncbi_link": "AR: 11835
Insl3: 16336"
  },
  {
    "caption": "mRNA expression levels extracted from RNA-seq data for Fkbp5 (D) in kidneys used for RNA-seq. Expression levels are normalized to WT ORX.",
    "ncbi_link": "Fkbp5: 14229"
  },
  {
    "caption": "mRNA expression levels extracted from RNA-seq data for , Odc1 (E) and Kap (F) in kidneys used for RNA-seq. Expression levels are normalized to WT ORX.",
    "ncbi_link": "Kap: 16483
Odc1: 18263"
  },
  {
    "caption": "(C) Western blot on cytoplasmic, nuclear and whole cell extracts derived from Hela cells transfected with human WT or W752R AR followed by stimulation with increasing concentrations of DHT. Both panels represent the same blot. The blot was cut in two parts and antibodies against HSP90 and Lamin A/C were used to confirm cellular fractionation of cytoplasmic and nuclear proteins. For AR visualization (upper panel), longer exposure time was used. # = residual AR expression (lower panel).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(B) AR occupancy (blue) and levels of the histone marks H3K27ac (green) and H3K27me3 (red) at ARBS within the regulatory regions of Fkbp5, Kap (both androgen-regulated in kidney) and Tox3 (androgen-regulated in prostate but not in kidney and hence used as a negative control) were assessed by ChIP-qPCR in kidneys from 13-week-old ARLmon/Y mice and WT males.",
    "ncbi_link": "AR: 11835
Fkbp5: 14229
Kap: 16483
Tox3: 244579"
  },
  {
    "caption": "(C) Representative pictures of immunofluorescence AR staining (green) in kidneys of castrated WT males and ARLmon/Y mice supplemented with vehicle or T. Nuclei are shown in blue.",
    "ncbi_link": "AR: 11835"
  },
  {
    "caption": "(B) Confocal fluorescence microscopy images of AR-WT-BirA* and AR W752R-BirA*expressing HEK293 cells treated in the presence of 50 µM biotin with 100 nM DHT or vehicle (ethanol) and with or without 0.03 µg/ml TET as indicated. AR-BirA*s were detected with anti-AR (red) and biotinylated proteins with fluorescently labeled streptavidin (green). Nuclei were visualized using DAPI.",
    "ncbi_link": "AR: 367
BirA: 948469"
  },
  {
    "caption": "Yeast pat1Δ mutants are unable to grow at 37°C while wild‐type (B4742) strain grows at 30°C (left panel) and 37°C (right). Growth at 37°C is restored in pat1Δ expressing AtPAT1. Serial dilutions of each yeast strain were plated on YPAD agar plates and grown at the indicated temperatures.",
    "ncbi_link": "pat1: 850440
PAT1: 834867"
  },
  {
    "caption": "Agarose gel electrophoresis of 5′ RACE PCR to detect capped transcripts of EIF4A1, UGT87A2 and EXPL1 in 14‐day‐old Col‐0 and pat1‐1.",
    "ncbi_link": "UGT87A2: 817566
EIF4A1: 820605
EXPL1: 823740
pat1: 850440"
  },
  {
    "caption": "pat1 mutants have a serrated leaf, semi‐dwarf phenotypePlants photographed at 4 weeks of growth in short day conditions, genotypes as indicated. Col‐0 and eds1‐2 plants and pat1‐1 and pat1‐1/eds1‐2, respectively, were placed in the middle of the same pots before the pictures were taken.",
    "ncbi_link": "eds1: 
pat1: 850440"
  },
  {
    "caption": "PR gene expression is elevated in mpk4‐2 and pat1‐1 mutants. Four‐week‐old plants were used for RNA extraction, followed by qRT‐PCR. Fold‐change in PR1 (gray bars) and PR2 (black) expression is relative to Col‐0, normalized to UBQ10. Standard error of the mean is indicated by errors bars (n = 3). Statistical significance between the mean values was determined by ANOVA followed by Fisher's LSD test, P‐values are only shown for mean values significantly different from Col‐0.",
    "ncbi_link": "mpk4: 
PR1: 
PR2: 
UBQ10: 
pat1: 850440"
  },
  {
    "caption": "pat1 is more resistant to colonization by P. syringae pv. tomato DC3000. Bacteria were syringe‐infiltrated and samples taken 3 days post‐infiltration. Data are shown as log10‐transformed colony‐forming units/cm2 leaf tissue (cfu/cm2). Standard error of the mean is indicated by errors bars (n = 4). Statistical significance between the mean values was determined by ANOVA followed by Fisher′s LSD test.",
    "ncbi_link": "pat1: 850440"
  },
  {
    "caption": "PAT1 protein is induced by PAMP treatment. Immunoblot detection of equal amounts of protein from Col‐0 seedlings at times in minutes as indicated following vacuum infiltration with 1 μM flg22 or water (180 min after infiltration). Immunoblots were probed with anti‐PAT1 antibodies. Negative control pat1‐1 was loaded for comparison. Coomassie brilliant blue protein loading control is indicated by CBB.",
    "ncbi_link": "pat1: 850440"
  },
  {
    "caption": "Elevated PR gene expression in pat1 mutants is suppressed by summ2‐8. Four‐week‐old plants were used for RNA extraction, followed by qRT‐PCR. Fold‐change in PR1 (gray bars) and PR2 (black bars) expression is relative to Col‐0, normalized to UBQ10. Standard error of the mean is indicated by errors bars (n = 3).",
    "ncbi_link": "PR1: 
PR2: 
summ2: 
UBQ10: 
pat1: 850440"
  },
  {
    "caption": "pat1 resistance to P. syringae pv. tomato DC3000 is suppressed by summ2‐8. Bacteria were syringe‐infiltrated and samples taken 3 days post‐infiltration. Data are log10‐transformed colony‐forming units/cm2 leaf tissue (cfu/cm2). Standard error of the mean is indicated by errors bars (n = 4).",
    "ncbi_link": "summ2: 
pat1: 850440"
  },
  {
    "caption": "14‐day‐old seedlings grown on ms plates were used for RNA extraction. Next, 1 μg of RNA from each sample was treated with XRN1 (NEB) or mock treated before RT‐qPCR. Data were normalized to ACT2, and transcript levels were compared between XRN1 and mock‐treated RNA for each genotype. Standard error of the mean is indicated by error bars (n = 4). Statistical significance between the mean values was determined by ANOVA followed by Fisher's LSD test.",
    "ncbi_link": "ACT2: 
XRN1: "
  },
  {
    "caption": "Phosphorylation of the PAT1 peptide SSFVSYPPPGSISPDQR, which include Ser208, in Col‐0 and mkk1/1‐summ2 before and after flg22 treatment. The phosphorylation stoichiometry is illustrated relative to Col PAT1 without flg22 treatment. The ratios were obtained using quantitative iTRAQ mass spectrometry.",
    "ncbi_link": "mkk1: 
summ2: "
  },
  {
    "caption": "(B) THP-1 cells were subjected to GABARAP knockdown and processed as in A.",
    "ncbi_link": "GABARAP: 11337"
  },
  {
    "caption": "(G) In vitro translated and radiolabeled [35S] myc-HA-TRIM16 was incubated with GST-galectin-8 in the presence (+) or absence (-) of flag-ULK1 and cold ATP, GST pulldowns were performed, and [35S] radiolabeled Myc-HA-TRIM16 in pulled-down material detected by PAGE and autoradiography. Amounts of GST fusion proteins are shown in coommassie brilliant blue (CBB)-stained gels. Data, means  SEM; n≥5, except for immunoblot quantifications where n≥3. *P < 0.05, †P ≥ 0.05 (t test or ANOVA).",
    "ncbi_link": "ULK1: 8408"
  },
  {
    "caption": "(C) IL-1β levels in 25k membrane fractions (pellets) from HeLa cells and their CRISPR knockout derivatives (TRIM16KO) that were reconstituted for IL-1β secretion and treated with 1mM LLOMe for 1 h.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(F,G) Sucrose density gradient analysis of 25k membranes. Note that mature IL-1β (mIL-1β) is recruited to and co-fractionates with TRIM16+, Sec22b+, and LC3-II+ membranes in TRIM16wt HeLa cells reconstituted with pro-IL-1β and pro-caspase 1, but not in TRIM16KO mutant cells.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(L) Co-IP analysis of interactions between deletion variants of flag-TRIM16 with GFP-Sec22b in HEK293T cells.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(M and N) IL-1β secretion complementation experiments of TRIM16KO cells with TRIM16 Sec22b-interacting and its Sec22b-nonbinding mutant shown.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "B ChIP gel images showing the relative enrichment by H3K4me3 in controls (n=9) and PD patients (n= 18). PCR amplified a 188-bp region of SNCA from intron 1 where H3K4me3 peak was at its optimum. Mouse IgG (mIgG) was used as control and the bands were normalized by unbiased amplification from respective inputs. Data information: Data represent mean ± standard error of the mean.",
    "ncbi_link": "SNCA: 6622"
  },
  {
    "caption": "D The graph represents the statistically significant difference of relative H3K4me3 enrichment between PD (n=7) and controls (n=6). Neuronal nuclei from PD brain samples show significantly higher enrichment of H3K4me3 at SNCA intron 1 (p=0.01) compared to controls. *P < 0.05. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. Two-tailed p-values were calculated for all. Data information: Data represent mean ± standard error of the mean.",
    "ncbi_link": "SNCA: 6622"
  },
  {
    "caption": "The corresponding α-synuclein levels C) were evaluated in SH-SY5Y cells expressing dCas9-5xGCN4 with (sgA-dCas9) or without scFV-sfGFP-JARID1A (sgA-dCas9-JA). C α-SYN levels in SH-SY5Y cells were also evaluated using western blot. The levels of α-SYN was normalized to β-actin. Significant reduction of α-SYN was observed in cells expressing JARID1A. Three independent repeats were performed. Percentage of reduction is shown in the graph. **P <0.01. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. Two-tailed p-values were calculated. Data information: All data are presented as mean ± SEM.",
    "ncbi_link": "Cas9: 
GFP: 
GCN4: 856709
JA: 5927
JARID1A: 5927"
  },
  {
    "caption": "E ChIP on H3K4me3 at the SNCA promoter between sPD1-1 lines after locus-specific epigenomic modulation. Differentiated cells were transiently transfected with either sgA-dCas9 5xGCN4-scFV-JARID1A or sg A-dCas9 5xGCN4-scFV-empty backbone vectors. A significant reduction in H3K4me3 at the SNCA promoter was observed in cells transfected with JARID1A. Data information: Three independent repeats were performed for both ChIP experiments. *P < 0.05; ****P<0.0001. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. One-tailed p-values were calculated for ChIP analysis",
    "ncbi_link": "Cas9: 
GCN4: 856709
JARID1A: 5927
SNCA: 6622"
  },
  {
    "caption": "F Western blot analysis of α-synuclein (α-SYN) levels in the cells under the same conditions as analyzed in (E). A significant decrease (56-66%) in α-SYN levels was observed in cells transfected with JARID1A. The normalized and relative expression of α-SYN in JARID1A transfected cells are shown as a percentage of control (transfected by empty backbone vector). Data information: Three independent repeats were performed for western blot experiments. *P < 0.05; ****P<0.0001. Data were analyzed using non-parametric t-test followed by Mann-Whitney post-hoc corrections. two-tailed p-value was calculated for western blot experiments. All data are presented as mean ± SEM.",
    "ncbi_link": "JARID1A: 5927"
  },
  {
    "caption": "F NALCN  knockdown suppresses invadopodia  formation reported by Cy3-fluorescent gelatin  degradation (arrows). Confocal  images (left) of Cy3  (red) and DAPI  (blue; nuclei) fluorescence in control (shCTL) and shNALCN  48 hours after plating the cells on gelatin. Bar diagram plot: NALCN  suppression causes significant decrease of the number of gelatin  degradation puncta counted within 48 h of incubation. Data information: The images: scale bar is 100 µm. Bar diagram plots show the degradation puncta per cell (F) mean±S.E.M. for N=5 (F) biological replicates per condition. **P<0.01, ***P<0.001, unpaired two-tailed Student's t-test.",
    "ncbi_link": "NALCN: 259232"
  },
  {
    "caption": "C-D [Ca2+]c oscillations reported by  Fluo-4  fluorescence in FBS-exposed  PC-3 cells pre-treated with siCTL (C) or siNALCN (D) for 72 hours. Top: sample traces from 8 different cells. Middle: POIs (top: grey background) are presented on enlarged plots to emphasize that NALCN  suppression abolishes \"pacemaker events\" observed in control (fitted red curves). Bottom: the galleries show every 3rd image during the POIs (middle: orange background). Scale bars: 10 μm.",
    "ncbi_link": "NALCN: 259232"
  },
  {
    "caption": "A-D Cytosolic Na+ concentration ([Na+]c) changes reported by ratiometric Na+  indicator SBFI  following (A-C) switch of extracellular Na+ concentration ([Na+]o) from 0 to 130 mM or (D) application of 1 µM thapsigargin  (TG). The effects of: (A) NALCN  knockdown, (B) extracellular Ca2+ concentration ([Ca2+]o) and (C) Ca2+  store depletion. Data information: Data show mean±S.E.M. The cartoons highlight experimental design and the plots show mean±S.E.M. traces (n=45-501) of SBFI  (olive) and Fura-2 (wine) fluorescence with the axes (∆R/R0) presented in corresponding colour.",
    "ncbi_link": "NALCN: 259232"
  },
  {
    "caption": "E-H Store-operated Ca2+  entry (SOCE)-induced changes of [Na+]c (SBFI) and [Ca2+]c (Fura-2). The effects of: NALCN  knockdown (E), the reverse-mode plasmalemmal Na+/Ca2+ exchanger (RM-NCX) inhibitor KB-R7943 (1 µM) either at [Na+]o=130 mM (F) or upon [Na+]o switch from 0 to 130 mM following SOCE activation (G), and knockdown of the mitochondrial Na+/Ca2+ exchanger, siNCLX (H). Data information: Data show mean±S.E.M. The cartoons highlight experimental design and the plots show mean±S.E.M. traces (n=45-501) of SBFI  (olive) and Fura-2 (wine) fluorescence with the axes (∆R/R0) presented in corresponding colour.",
    "ncbi_link": "NALCN: 259232
NCLX: 80024"
  },
  {
    "caption": "I SOCE augments NALCN-mediated Na+ influx  (top) by addressing NALCN  to plasma membrane (bottom). Data information: Plots (I, top) compare mean rates of Na+ influx  induced by [Na+]o-switch (n=283-360) and SOCE (n=180-216), and their shNALCN-sensitive fractions. Immunoblotting  (I, bottom) compares NALCN expression  in total cell lysates and biotinylated fractions before and after SOCE induction. Numbers show (in corresponding colour) mean values (n=3) of NALCN  protein levels (band intensity) normalized to N-Cadherin, Calnexin  and β-actin.",
    "ncbi_link": "NALCN: 259232"
  },
  {
    "caption": "D Suppression of NCLX  with siNCLX attenuates [Ca2+]c oscillations (Fluo-4). Data information: In D, mean signal temporal densities during highlighted periods were compared in control (n=18) and following 48 h pre-treatment with siNCLX (n=17). Bar diagram plots: mean±S.E.M. n= number of cell, ***P<0.001, unpaired two-tailed Student's t-test. Cartoons (left) highlight experimental design and assessed signaling pathways. Note that Na+ delivered to the cytosol  by NALCN, on the one hand, activates RM-NCX, while on the other hand, is exchanged by NCLX  to Ca2+ thus restricting elevation of [Ca2+]mito and, hence, production of superoxide  (O2-) and H2O2, which is known to inhibit SERCA, RM-NCX and SOCE elements.",
    "ncbi_link": "NALCN: 259232
NCLX: 80024"
  },
  {
    "caption": "E Plot: mean rates of secretion calculated as signal mass (cyan, left) per second. Data information: Data (E): mean±S.E.M. for siCTL (n=35), siNALCN (n=40), Control (n=45), EGTA-AM  (n=35) and BAPTA-AM  (n=62). n= number of cell, ***P<0.001; and n.s., not significant, unpaired two-tailed Student's t-test.",
    "ncbi_link": "NALCN: 259232"
  },
  {
    "caption": "D Left: Dorsal (top) and ventral (bottom) images of bioluminescence from mice  31 days after intra-tibial  injection of control (shCTL: PC-3 Luc-shCTL) or NALCN  depleted cells (shCTL: PC-3 Luc-shNALCN). Right: statistical comparison of total photon fluxes between the two groups of 10 mice  (c.p.s.: count of photons per second±SD). Data information: *P<0.05, **P<0.01, and n.s., not significant, two-tailed Mann-Whitney U test.",
    "ncbi_link": "Luc: 
NALCN: 259232"
  },
  {
    "caption": "E Left: x-ray  3D images obtained from mice  8 weeks after intracardiac injections with control (PC-3 Luc) and cells stably overexpressing NALCN  (+hNALCN). Right: box plots compare the incidence and total volume of bone lesions between the two groups of 11 mice: central band shows the mean, the boxes show lower and upper quartiles and whiskers show maximum data values. Data information: Red numbers and/or arrows in the images depict tumour take incidence/bone lesions. *P<0.05, **P<0.01, and n.s., not significant, two-tailed Mann-Whitney U test.",
    "ncbi_link": "Luc: 
NALCN: 259232"
  },
  {
    "caption": "B) Western blots showing absence of mitochondrial proteins from the different mitochondrial complexes: NDUFB8 (complex I), SDHA (complex II), UQCRC2 (complex III) and MTCO-1 (complex IV), in senescent (10 days after 20Gy X-ray) Control and Parkin-expressing MRC5 fibroblasts. Data is representative of 3 independent experiments;",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "C) Cellular oxygen consumption rates (OCR) in senescent (10 days after 20Gy X-ray) Control and Parkin-expressing MRC5 fibroblasts. Data were obtained using Seahorse XF24 analyzer and shows mean±S.D. n=4 technical repeats (representative of 2 independent experiments);",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "D) Representative 3D EM pictures of senescent (20 days after 20Gy X-ray) Parkin-expressing MRC5 fibroblasts with or without CCCP. Mitochondria are in red, the nucleus in blue;",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "E) Representative images of cell size, Sen-β-Gal activity (blue cytoplasmic staining), macro-H2A foci and SDHA immunofluorescence in proliferating and senescent (10 days after 20Gy X-ray) Parkin- expressing MRC5 fibroblasts;",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "F) Quantification of ROS levels (DHE fluorescence), Sen-β-Gal positive cells and Senescence-associated heterochromatin foci (SAHF) observed by DAPI in proliferating and senescent (10 days after 20Gy X-ray) Control and Parkin-expressing MRC5 fibroblasts. Data are mean±S.E.M of n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "G) Representative western blots showing p21 and p16 expression in proliferating and senescent (10 days after 20Gy X-ray) Control and Parkin-expressing MRC5 fibroblasts. Data are representative of 3 independent experiments;",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "H) Secreted protein measured in a cytokine array (RayBiotech) of a variety of inflammatory proteins in proliferating and senescent (10 days after 20Gy X-ray) Parkin-expressing MRC5 fibroblasts. Data are mean±S.E.M of n=3 independent experiments. Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "A) Representative images of colony assays of wild-type and PGC-1β -/- MEFs grown at 3% or 21% O2 (10 days after seeding 5,000 cells/well). Data are representative of 3 independent experiments;",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "B) Effect of 3% or 21% O2 and X-ray irradiation (at 3% O2) on the percentage of Ki67 (at day 6) and Sen-β-Gal positive cells (at day 10) and number (N) of 53BP1 foci (at day 6) in wild-type and PGC-1β -/- MEFs. Data are mean±S.E.M of n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "C) Representative images of Sen-β-Gal activity (blue cytoplasmatic staining), Ki-67 and 53BP1 foci in proliferating and senescent wild-type and PGC-1β-/- MEFs (scale bar=10µm);",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "D) mRNA expression of PGC-1β CXCL-1 and p16 in proliferating and senescent (10 days after 10Gy X-ray) wild type and PGC-1β-/- MEFs. Data are mean±S.E.M. of n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "p16: 12578
CXCL-1: 14825
PGC-1β: 170826"
  },
  {
    "caption": "E) Effects of overexpression of PGC-1β on the percentage of Ki67 and Sen-β-Gal positive cells, number (N) of 53BP1 foci and percentage change of mitochondrial mass (NAO intensity) in proliferating and senescent (2 days after 10Gy X-ray) MEFs cultured at 3% O2. Data are mean±S.E.M of n=3 independent experiments. Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "C) Effect of 100nM rapamycin on mitochondrial mass (measured by NAO fluorescence) 2-4 days following replication exhaustion (RS) or genotoxic stress (generated by X-ray irradiation, Etoposide, Neocarcinostatin (NCS), H2O2 or telomere dysfunction (TRF2ΔBΔM)) in a variety of cell lines. Data are mean from 3 independent experiments per cell line or treatment;",
    "ncbi_link": "TRF2: 7014"
  },
  {
    "caption": "A) ROS levels (DHE intensity) and mean number (N) of yH2A.X foci after mTOR knockdown (72 hours) in proliferating and senescent (2 days after 20Gy X-ray) MRC5 fibroblasts. Data are mean±S.E.M of n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "mTOR: 2475"
  },
  {
    "caption": "D) ROS levels (DHE intensity) in proliferating and senescent (3 days after 10Gy X-ray) wild-type and PGC-1β-/- MEFs (top) and PGC-1β overexpressing MEFs (bottom). Data are mean±S.E.M. of n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "E) (top) Representative images and quantification of immunofluorescence staining against FLAG-PGC-1β (red) and 53BP1 (green) in proliferating and senescent (2 days after 10Gy X-ray) PGC-1β overexpressing MEFs cultured at 3% O2, with or without 250µM of the antioxidant Trolox (scale bar=10µm). Data are mean±S.E.M, n=3 independent experiments; Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "PGC-1β: 170826"
  },
  {
    "caption": "F) (top) Effect of overexpression of mutated Rheb (N153T) and (bottom) effect of 100nM rapamycin on the mean number (N) of 53BP1 foci in proliferating and senescent (3 days after 10Gy X-ray) wild-type and PGC-1β -/- MEFs. Data are mean±S.E.M of n=3 independent experiments (at least 125 cells were analyzed per condition). Asterisks denote statistical significant P<0.05 One-way ANOVA.",
    "ncbi_link": "PGC-1β: 170826
Rheb: 19744"
  },
  {
    "caption": "j) Effect of 4 months rapamycin feeding on mRNA expression of the SASP components CXCL1, CXCL5 and Inhibin A in liver tissue of 16 months old mice with or without 4 months rapamycin treatment. Data are from n=5 mice per condition; Asterisks denote statistical significant P<0.05 using Two-tailed t-test.",
    "ncbi_link": "CXCL1: 14825
CXCL5: 20311
Inhibin A: 16322"
  },
  {
    "caption": "K) Mean number of TAF in hepatocytes of wild type and PGC-1-β-/- mice with 18 months of age. Data are mean±S.E.M of n=4 mice per group; Asterisks denote statistical significant P<0.05 using Two-tailed t-test.",
    "ncbi_link": "PGC-1-β: 170826"
  },
  {
    "caption": "A. Eight-day-old seedlings of WT, bri1 and pRPS5a:BRI1:YFP;bri1. Scale bar 1 cm.",
    "ncbi_link": "bri1: 830095"
  },
  {
    "caption": "B. Root-length measurements of 10-day-old bri1-116, bes1-D and pRP5SA:BRI:YFP;bri1-116 seedlings compared to the wild type. Symbols represent the mean of more than 20 plants, from 3 independent experiments. Bars show standard deviation. Straight lines represent the linear regression applied to each curve starting with day 4 post germination. In this way the root growth rate can be extracted for each phenotype (See Table EV7).",
    "ncbi_link": "BRI: 830095
bri1: 830095"
  },
  {
    "caption": "C. Confocal images of 8-day-old wild type WT, bri1-116 and pRP5SA:BRI:YFP;bri1-116 roots stained with PI. Green lines label the end of the transition zone and the yellow lines label the first root hair (end of elongation zone). The inset shows pRP5SA expression domain of an 8-day-old pRP5SA:BRI:YFP;bri1-116 seedling. Green line labels the end of the meristematic zone, which coincides with the end of pRP5SA expression domain. Scale bars correspond to 100 microns.",
    "ncbi_link": "bri1: 830095"
  },
  {
    "caption": "C-H. Main relationships as in Fig. 2C-E between experimental values of the phenotypic traits used to assess the mechanism of differentiation in bri1-116 mutant (C,E,G) and pRP5SA:BRI:YFP;bri1-116 line (D,F,H) for the epidermis (left large plot) and cortex (right inset plot). Each circle denotes data extracted from a single root (n=126 (epidermis) and n=25 (cortex) for bri1-116 and n=90 (epidermis) and n=17 (cortex) for pRP5SA:BRI:YFP;bri1-116, see Table EV1, pooled from 6, 8 and 10 day-old seedlings for epidermis and from day 6 for cortex (data in Table EV5)). In G, H, the slope of the linear regression is 2.13±0.04 for bri1-116 and 2.53±0.04 for pRP5SA:BRI:YFP;bri1-116. Pearson correlation coefficient r is indicated and p-value (p, using standard Person correlation test). In E, bri1-116 epidermal data do not conform to normal distributions.",
    "ncbi_link": "bri1: 830095"
  },
  {
    "caption": "(c) Knockdown of LC3 or Beclin 1 potentiated Wnt signalling. (n = 3; asterisk, P 0.05).",
    "ncbi_link": "Beclin 1: 8678
LC3: 440738///81631///84557"
  },
  {
    "caption": "(d) Atg5 knockout enhanced Wnt signalling. TopFlash reporter activity induced by Wnt3a CM in Atg5−/− or wild-type MEFs. Results are means ± s.d. after normalization to Renilla luciferase activity. (n = 3; asterisk, P 0.05).",
    "ncbi_link": "Wnt: 
Atg5: 11793"
  },
  {
    "caption": "(b) The half-life of Dvl2 was prolonged in Atg5−/− cells. MEFs were subjected to starvation (starv.) for the indicated durations and harvested for immunoblotting with the indicated antibodies. Dvl2 levels were quantified (right panel). Autophagy induction is indicated by the levels of LC3 II and p62 degradation.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c) Reintroduction of Atg5 in Atg5−/− MEFs restored starvation-induced Dvl2 degradation. MEFs infected with recombinant adenovirus expressing GFP or Atg5 were starved for the indicated durations, and the cell lysates were subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(d) Dvl2 degradation was slowed down in Atg7−/− MEFs. MEFs were subjected to starvation for the indicated durations and harvested for immunoblotting with the indicated antibodies. Dvl2 levels were quantified (right panel).",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(e) The continued degradation of Dvl2 in Atg5−/− cells is proteasome-dependent. MEFs were starved for 2, 4 or 8 h with MG132 (1 μM) or BFA1 (0.1 μM) for different durations, followed by anti-Dvl2 immunoblotting to detect endogenous Dvl2 protein levels. Tubulin served as a loading control. Uncropped images of blots are shown in Supplementary Information, Fig. S8.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Immunoelectron microscopy analysis of HeLa cells transfected with Flag-Dvl2 under nutrient-rich or starvation conditions. The arrowheads indicate Flag-Dvl2. Scale bars, 1 μm (left); 250 nm (right).",
    "ncbi_link": "Dvl2: 1856"
  },
  {
    "caption": "(b) Localization of endogenous Dvl proteins (red) and GFP-LC3 (green) in GFP-LC3 stable HeLa cells in nutrient-rich medium or under starvation (starv.) conditions with BFA1 for 4 h. The right panel shows the percentage co-localization between Dvls and GFP-LC3-positive dots. Scale bar, 5 μm.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(g) The LC-3-binding motif is important for the Dvl2-LC3 interaction. GST-LC3-immobilized beads were incubated with the lysates from the cells expressing wild-type (WT) Dvl2 or the W444A, I447A mutant (MUT); the pulldowns were then subjected to anti-haemagglutinin (anti-HA) immunoblotting. Uncropped images of blots are shown in Supplementary Information, Fig. S8.",
    "ncbi_link": "Dvl2: 1856"
  },
  {
    "caption": "(a) Interaction between LC3 and wild-type Dvl2 or its point mutants.",
    "ncbi_link": "Dvl2: 1856"
  },
  {
    "caption": "(b) Co-localization of GFP-LC3, p62 and Dvl in HeLa GFP-LC3 stable cells on starvation. Proteins visualized by immunofluorescence with anti-GFP (green), anti-p62 (blue) and anti-Dvl (red) antibodies. Scale bar, 10 μm.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(c) p62 knockdown slows the degradation of Dvl2 on starvation. HEK-293T cells were transfected with p62 siRNA. At 48 h after transfection, cells were subjected to starvation for various times. The cell lysates were subjected to immunoblotting with the antibodies indicated. Uncropped images of blots are shown in Supplementary Information, Fig. S8.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(b) In vitro ubiquitylation of Dvl2 by the pVHL E3 ligase complex including pVHL, Elongin B, Elongin C, Rbx1 and Cul2. In vitro-translated Flag-Dvl2 was incubated with or without purified E1, E2 and E3 ligase complex, Elongin C and pVHL. The reaction was subjected to anti-Flag immunoprecipitation. Dvl2 ubiquitylation was examined by using anti-ubiquitin immunoblotting.",
    "ncbi_link": "Elongin C: 6921
VHL: 7428"
  },
  {
    "caption": "(d) Starvation elevates Dvl2-Cul2 interaction. After co-transfection with Myc-Cul2 and Flag-Dvl2 for 36 h, HEK-293T cells were cultured in nutrient-rich medium or starved with BFA1 (0.1 μM) for 4 h. Cells were harvested for anti-Myc immunoprecipitation followed by anti-Flag immunoblotting. Total protein expression was confirmed by immunoblotting with whole-cell lysates.",
    "ncbi_link": "Cul2: 8453"
  },
  {
    "caption": "(a, b) Depletion of Beclin 1 by shRNA promotes growth in soft agar. SW480 cells stably expressing Beclin 1 shRNA or control shRNA were seeded in soft agar and treated with or without Dkk (a); the colonies were then scored after 10 days (b). Numbers in bars indicate the numbers of colonies. Results are means ± s.d. (n = 4). (Asterisk, P 0.05). Scale bar, 200 μm.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(A) Survival graphs of newborn pups from breeding of Rab11aFl/+;Rab11b+/-;Villin-Cre and Rab11aFl/+;Rab11b+/- (or Rab11aFl/+;Rab11b-/-) mice. The total number of pups for each genotype was labeled next to the corresponding curve. The graph represents over 6 independent litters from three different mating pairs.",
    "ncbi_link": "Cre: 2777477
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(B) Western blots for Rab11a and Rab11b using small intestinal lysates prepared from adult wild type (WT, lane 1), Rab11aFl/Fl;Villin-CreER (aKO, lane 2) 2 days after tamoxifen treatment, Rab11b-/- (bKO, lane 3), and Rab11aFl/Fl;Rab11b-/-;Villin-CreER (DKO) mice 1-day (lane 4), 2-day (lane 5), and 3-day (lane 6) after tamoxifen treatment. All mice were given a single tamoxifen injection. β-actin was used as loading control. Results represent more than 3 independent experiments.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(C) H. & E. staining of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice, before and after tamoxifen injection. Images represent jejunum tissues collected 1, 2, and 3 days following tamoxifen injection. Experiments were repeated over 5 times using independent litters (n>10). Scale bars, 50 μ",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(D) Alkaline phosphatase (AP) staining was performed on intestinal tissue sections of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice that were treated with corn oil or with tamoxifen. Results represent at least 3 independent experiments. Scale bars, 50 μm.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(F) Alcian blue staining was performed on adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before or 1 to 3 days after tamoxifen injection. Results represent at least 3 independent experiments. Scale bars, 100 μm. (G) Quantification of the number of alcian blue positive cells per crypt-villus axis in mice of various genotypes. Data represent average values of approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(H) Immunofluorescent staining for lysozyme and E-Cad was performed on adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before and after tamoxifen injection. Experiments represent 3 independent replicates. Scale bars, 50 μm. (I) Quantification of lysozyme fluorescent signal abundance per crypt in mice of various genotypes. Data represent approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(B) Immunohistochemistry for Ki67 staining was performed on intestinal sections of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before and after tamoxifen injection. Experiments represent 3 independent replicates. Scale bars, 50 μm. (C) Quantification of ratio of Ki67+ cells over total epithelial cells per crypt-villus axis in DKO mice before and after tamoxifen treatment. Data represent approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(D) Immunofluorescent staining for pHH3 and E-Cad was performed on intestinal sections of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before and after tamoxifen injection. Experiments represent 3 independent replicates. Scale bars, 50 μm. (E) Quantification of ratio of pHH3+ cells over total IECs per crypt in DKO mice before and after tamoxifen treatment. Data represent approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(H) Immunohistochemistry for Olfm4 was performed on intestinal sections of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before and after tamoxifen injection. Experiments represent 3 independent replicates. Scale bars, 50 μm. (I) Quantification of Olfm4+ cell number per crypt in DKO mice before and after tamoxifen treatment. Data represent approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(L) Immunohistochemistry for c-Myc was performed on intestinal sections of adult Rab11aFl/Fl;Rab11b-/-;Villin-CreER mice before and after tamoxifen injection. Experiments represent 3 independent replicates. Scale bars, 50 μm. (M) Quantification of c-Myc+ cell number per crypt-villus axis in DKO mice before and after tamoxifen treatment. Data represent approximately 10-15 different microscopic fields taken from 3 mice per condition.",
    "ncbi_link": "Cre: 2777477
ER: 13982
Rab11a: 53869
Rab11b: 19326
Villin: 22349"
  },
  {
    "caption": "(F) Co-IP assays were performed in HEK293T cells to validate the association between 3×Flag-Rab11a, 3×Flag-Rab11b and endogenous KIF11. Lane 1: input lysate; lane 2: flow through after co-IP; lane 3-5: 3 washes; lane 6: on beads; and lane 7: immunoprecipitation elutes. Cells transfected with 3×Flag empty vector were uses as a negative control. Experiments repeated over 6 times.",
    "ncbi_link": "Flag: "
  },
  {
    "caption": "(G) Cells were transfected with mCherry-tagged WT, Rab11-S25N, and Rab11-S20V, fixed and stained for endogenous KIF11 (grey) and pericentrin (green). The mCherry signal (red) represents direct fluorescent signal visualized under confocal microscope. Arrows denote position of spindle poles defined by pericentrin. Images represent three independent experiments. Scale bars, 10 μ (H) Quantification of the percentage of bipolar, monopolar, or multipolar (3 or more) spindles observed in mitotic cells identified from each microscopic field. Data represents 10-20 independent fields per condition from 3 experiments.",
    "ncbi_link": "mCherry: 
Rab11: "
  },
  {
    "caption": "(B-C) HEK293T cells were transiently transfected with 3×Flag-Rab11a (or 3×Flag-Rab11b) and V5-tagged KIF11 truncates. Lysates were immunoprecipitated by anti-Flag antibody, and probed by an anti-V5 antibody to assess intracellular associations. Cells transfected by V5 empty vector were used as a negative control.",
    "ncbi_link": "Flag: 
Rab11a: 
Rab11b: 
V5: 
KIF11: 3832"
  },
  {
    "caption": "(H) HEK293T cells were transiently transfected with 3×Flag-Rab11a, treated with nocodazole (100 ng/ml) or vehicle overnight, and lysates were used for Flag immunoprecipitation followed by immunoblot for KIF11. Quantification of co-immunoprecipitated KIF11 was normalized to input KIF11 from control (n=6) and nocodazole-treated (n=9) cells.",
    "ncbi_link": "Flag: 
Rab11a: "
  },
  {
    "caption": "(L) KIF11 co-IP analysis were performed using WT and RAB11-KD CaCo2 cell lysates. The immunoprecipitates were probed for CLIP1, ZW10, CCAR1, USO1, and CCNB1. Experiments represent 2-4 replicates for each target.",
    "ncbi_link": "RAB11: 9230///8766"
  },
  {
    "caption": "Representative apoptotic genes, Anxa1, Anxa5, Bcl2l1 which were highly elevated in DKO intestines. n=3 mice for each genotype.",
    "ncbi_link": "Anxa1: 16952
Anxa5: 11747
Bcl2l1: 12048"
  },
  {
    "caption": "(B) In vitro kinase assays showing Munc18-1 phosphorylation by ERK. Radioactive phosphoblot (32P) and immunoblot (IB) of in vitro ERK kinase assay using immunoprecipitatedMunc18WT, Munc184A (M18T78A,S158A,S241A,T574A), Munc183A (M18S158A,S241A,T574A), and Munc18AA (M18S241A,T574A) from HEK293T cells incubated with recombinant ERK2. The phosphoblot shows phosphorylated Munc18-1 (pMunc18-1) and auto-phosphorylated ERK2 (pERK2).(C) Quantification of phospho-Munc18-1 intensity in wild-type and Munc18AA mutant expressed as the amount of 32P incorporation in Munc18-1 normalized to total Munc18-1 levels. Phosphorylation of Munc18WT was set to 100%. (Munc18WT: 100±3%; Munc18AA: 24±2%, n=3, * p = 0.01).",
    "ncbi_link": "Munc18: 20910"
  },
  {
    "caption": "Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT, M18S241A or M18S241D. Electrophysiology recordings were performed between DIV14-17.(A) Amplitude of excitatory synaptic response (EPSC) (M18WT: 1.37±0.21 nA, n=35; M18S241A: 2.53±0.31 nA, n=45; M18S241D: 0.24±0.05 nA, n=17, ***p<0.001, **p<0.01, *p<0.05).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT, M18S241A or M18S241D. Electrophysiology recordings were performed between DIV14-17.(B) Percentage of cells that do not respond to electrical stimulation (M18WT: 15.5%; M18S241A: 0%; M18S241D: 56.9%). These cells are not included in (A). Insert: representative recording of single EPSCs. Scale bar represents 10 ms and 0.5 nA.",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT, M18S241A or M18S241D. Electrophysiology recordings were performed between DIV14-17.(C) Typical examples of spontaneous vesicle release. Scale bar represents 0.1 s and 25 pA.(D) Spontaneous release frequency (M18WT: 7.05 ± 1.28 Hz, n=32; M18S241A: 14.26 ± 2.04 Hz, n=37; M18S241D: 0.64 ± 0.29 Hz, n=11; ***p<0.001, **p<0.01).(E) Amplitude of spontaneous release events (M18WT: 15.40 ± 1.06 pA, n=17; M18S241A: 15.03 ± 0.61 pA, n=20; M18S241D: 10.98 ± 0.72 pA, n=10; **p<0.01).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT, M18S241A or M18S241D. Electrophysiology recordings were performed between DIV14-17.(F) Size of the readily releasable pool (RRP) assessed with single hyperosmotic sucrose application (500 mM, 3.5 s, M18WT: 0.74 ± 0.15 nC, n=7; M18S241A: 1.6 ± 0.33 nC, n=10; M18S241D: could not be determined; * p < 0.05).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT, M18S241A or M18S241D. Electrophysiology recordings were performed between DIV14-17.(G) Neurons were stimulated with two consecutive pulses with varying inter-stimulus interval to assess release probability. Paired pulse ratio calculated as ratio of the second to the first synaptic response is plotted as function of inter-stimulus interval (M18WT, n=25; M18S241A, n=19; M18S241D, n=17); * p < 0.05, ** p < 0.01). All data are expressed as mean ± SEM. See also Figure EV2 and EV3.",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(A-F) Munc18-1 protein levels were measured in glia free cultures of munc18-1null mutant neurons expressing M18WT, M18S241A or M18S241D.(A) Typical examples showing Munc18-1 protein localization and intensity in neurites of M18WT, M18S241A or M18S241Dneurons. MAP2 in blue, VAMP2 in red and Munc18-1 in green. Scale bar represents 2 m.(B) Mean somatic Munc18-1 intensity (M18WT: 1682 ± 206 a.u., n = 46; M18S241A: 1719 ± 238 a.u., n = 36; M18S241D: 582 ± 98 a.u., n = 33; *** p < 0.001).(C) Mean synapticMunc18-1 intensity (M18WT: 1281 ± 161 a.u.; M18S241A: 1390 ± 180 a.u.; M18S241D: 210 ± 30 a.u.; *** p < 0.001).(D) Mean synapticMunc18-1 intensity as a function of radial distance from the soma.",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(A-F) Munc18-1 protein levels were measured in glia free cultures of munc18-1 null mutant neurons expressing M18WT, M18S241A or M18S241D.(E) Mean synaptic Munc18-1 intensity in cultures with 3 times the standard number of neurons to increase network activity (M18WT: 1072 ± 123 a.u., n = 36; M18S241A: 1480 ± 170 a.u., n = 32; M18S241D: 251 ± 70 a.u., n = 34; * p < 0.05, *** p < 0.001).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(A-F) Munc18-1 protein levels were measured in glia free cultures of munc18-1 null mutant neurons expressing M18WT, M18S241A or M18S241D.(F) Mean synaptic Munc18-1 intensity in cultures treated with GABAA receptor antagonist Bicuculline (40 μM, 48 h). (M18WT: 761 ± 121 a.u., n = 26; M18S241A: 1482 ± 150 a.u., n = 31, ** p < 0.01).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(H) Western Blot of lysates from high-density neuronal cultures from munc18-1 null mutant mice rescued with M18WT, M18S241A or M18S241D. Prior to lysis, cells were treated for 6 h with MG132 (10 M) or DMSO as control. Western Blots were stained for Munc18-1 and tubulin as loading control.(I) Quantification of (H). Munc18-1 levels were normalized to tubulin levels. Effect of proteasome inhibition was quantified as ratio between MG132 and DMSO treatment of each mutant (M18WT: 1.62 ± 0.41; M18S241A: 1.26 ± 0.16; M18S241D: 7.53 ± 1.17, n = 3; **p<0.01).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(J) Ubiquitination of different Munc18-1 mutants in HEK293T cells. Western Blot of denatured Munc18-1 immuno-precipitations from cells expressing Munc18-1 mutants and HA-tagged ubiquitin. Prior to lysis, cells were treated for 8 h with MG132 (10 M). Ubiquitin covalently attached to Munc18-1 can be observed as a smear above the characteristic 68 kD Munc18-1 band on Western blots stained for HA-tag.(K) Quantification of immuno-precipitation in (J). Level of Munc18-1 ubiquitination was quantified as ratio of immunoprecipitated ubiquitin and Munc18-1 levels. M18WT was set to 1 (M18WT: 1 ± 0.06; M18S241A: 0.84 ± 0.57; M18S241D: 2.70 ± 0.07, n = 3; **p<0.01). All data are expressed as mean ± SEM.",
    "ncbi_link": "Munc18-1: 20910
Ubiquitin: 22190///22186///78294///22187"
  },
  {
    "caption": "(A) Western blot from whole cell lysate of munc18-1 null mutant neurons rescued with M18WT and incubated with WIN55,212-2 (5 M) for 30 s. Cells were harvested after the indicated time. CB1R activation leads to a rapid and transient increase in pERK activity.",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(B-D) Hippocampal autaptic neurons of munc18-1null mutant mice were rescued with lentiviruses expressing M18WT or M18S241A. CB1R agonist WIN55,212-2 (5 M) was applied at t = 60 s for 30 s.(B) Amplitude of excitatory synapse response normalized to t=0 s. Neurons were stimulated by a single action potential every 30 s for 4 min (M18WTn = 21, M18S241An = 24, *p<0.05). Note the broken y-axis.(C) Ratio of the frequency of spontaneous release events after (t = 180 s) and before (t = 0 s) WIN55,212-2 application (M18WT: 58.0 ± 2.3 %, n = 21; M18S241A: 84.2 ± 5.6 %, n = 24, * p < 0.05).(D) Ratio of amplitude of spontaneous release events after (t=240 s) and before (t=0 s) WIN55,212-2 application (M18WT: 85.0 ± 2.7 %, n = 21; M18S241A: 83.1 ± 2.6 %, n = 24).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(E-G) Autaptic neurons of munc18-1 null mutant mice rescued with lentiviruses expressing M18WT were superfused with WIN55,212-2 (1 M), WIN55,212-2 (1 M) plus AM251 (1 M) or vehicle only (DMSO).(E) Amplitude of excitatory synapse response normalized to t=0 s. CB1R agonist WIN55,212-2 (1 M) or vehicle only (DMSO) were applied at t=60 s for 30 s. (WT + WIN n = 13; WT + DMSO n = 16, * p < 0.05). Note the broke Y-axis.(F) Paired pulse ratio (20 ms interval) at t = 0 and t = 240 s in M18WT neurons superfused with CB1R agonist WIN55,212-2 (1 M) at t = 60 s for 30 s. WIN55,212-2 application increases PP ratios indicative of a reduction of synaptic release probability (t = 0 s: 0.94 ± 0.1, n = 13; t = 240 s: 1.36 ± 0.2, n = 16, * p < 0.05).(G) Amplitude of excitatory synapse response normalized to t = 0 s. CB1R agonist WIN55,212-2 (1 M) was applied together with the CB1R antagonist AM251 (1 M) at t = 60 s for 30 s. (WT + WIN n = 13, same trace as 6F; WT + WIN + AM251 n = 15, * p < 0.05). Note the broke Y-axis.",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": "(H-J) Hippocampal autaptic neurons of munc18-1 null mutant mice were rescued with M18WT or M18S241A. mGluR2/3 agonist LY379268 (1 M) was applied by bath-perfusion for 4 min.(H) Ratio of amplitude of evoked release events after (t = 240 s) and before (t = 0 s) LY379268 application (M18WT: 55.0 ± 4.7 %, n = 14; M18S241A: 81.1 ± 3.6 %, n = 16, * p < 0.05).(I) Ratio of frequency of spontaneous release events after (t = 240 s) and before (t = 0 s) LY379268 application (M18WT: 63.0 ± 5.7 %, n = 14; M18S241A: 85.1 ± 3.4 %, n = 16, * p < 0.05).(J) Ratio of the amplitude of spontaneous release events after (t = 240 s) and before (t = 0 s) WIN55,212-2 application (M18WT: 81.0 ± 1.3 %, n = 14; M18S241A: 82.1 ± 3.3 %, n = 16).",
    "ncbi_link": "munc18-1: 20910"
  },
  {
    "caption": " B An Integrative Genomics Viewer (IGV) screenshot of the Notch de novo TE insertion site from sample P47 (clonal neoplasia) and its head control, sample P48. Bars represent sequencing reads. Reads supporting the TE insertion are colored according to homology to a specific TE insertion sequence. Multiple colors at a putative insert site frequently indicate homology to different reference copies of the same TE family. Two types of supporting reads can be seen: soft-clipped reads - spanning the insertion site and mapping partially to the reference genome and partially to the TE, and mate pair support reads - flanking the insertion site and mapping to the reference genome but with mates (not seen) mapping to the TE. ",
    "ncbi_link": "Notch: 31293"
  },
  {
    "caption": " C The distribution of somatic insertions with estimated cell fraction higher or lower than Notch-inactivating mutations for the most represented LTR-elements (rover and copia) and LINE-like I-elements. (p-values were calculated with Fisher's exact test, two-tailed, n= number of insertions) ",
    "ncbi_link": "Notch: 31293"
  },
  {
    "caption": " A Heatmaps representing normalized TE expression levels (in log2(TPM), transcripts per million) and mobility (log2(insertion counts)) in Pros>2xGFP midguts. TEs with TPM values below 0.05 (log2(TPM)< -4.3) are not depicted. Crossed out cells represent no somatic insertions of that family identified. ",
    "ncbi_link": "GFP: 
Pros: 41363"
  },
  {
    "caption": "a, Pancreatic sections stained with Atg7, LC3 and p62 showing Atg7−/− next to Atg7+/+ regions after Pdx-Cre-mediated recombination. Right-side images are cropped and magnified regions (boxed) from left-side images. The magnification is × 2.5.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "b, Haematoxylin and eosin (HE), p53 and caspase-3 staining of exocrine tissue in Atg7+/+ and Atg7−/− pancreases.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "c, Quantification (median, s.e.m.) of p53 and caspase-3 activation in Atg7-deficient acinar tissue.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "d, Kaplan-Meier analysis comparing overall survival of mice either wild type (blue) or Atg7−/− (red) in the pancreas. Mantel-Cox test was used for statistics. 'n/a', 14/16 mice were killed >500 days when completely healthy.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "e, Biochemical analysis of endocrine function in moribund Atg7−/− or age-matched healthy control mice. Detailed information about the mice is tabulated. A Mann-Whitney U-test was used for statistics. Scale bars: 50 µm. **P 0.01 and ***P 0.001.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "a, Alcian blue/PAS (AB/PAS) staining in pancreases from 150-day-old Atg7-proficient or Atg7-deficient KrasG12D/+ mice (wild-type mice with expression of KrasG12D in their pancreases).",
    "ncbi_link": "Atg7: 74244
Kras: 16653"
  },
  {
    "caption": "c, d, Kaplan-Meier analysis comparing overall survival (c) or PDAC-free survival (d) of Atg7+/+ (blue) or Atg7−/− (red) KrasG12D/+ mice.",
    "ncbi_link": "Atg7: 74244
Kras: 16653"
  },
  {
    "caption": "c, d, Kaplan-Meier analysis comparing overall survival (c) or PDAC-free survival (d) of Atg7+/+ (blue) or Atg7−/− (red) KrasG12D/+ mice",
    "ncbi_link": "Atg7: 74244
Kras: 16653"
  },
  {
    "caption": "e, PanIN grading of pancreases from 150-day-old Atg7+/+ or Atg7−/− Pdx-Cre KrasG12D/+ mice. Values are mean and error bars are s.d. b, e, A Mann-Whitney U-test was used for statistics.",
    "ncbi_link": "Atg7: 74244
Kras: 16653"
  },
  {
    "caption": "g, PDAC-free survival of autophagy-proficient (blue) and Atg5-deficient (red) KrasG12D/+ mice. d, g, Median survival ± s.d. and male/female (m/f) ratio are provided. 'n/a', no animals succumbed to PDAC. A log-rank test (Mantel-Cox) was used for statistics. a, f, Scale bars: 500 µm (a), 50 µm (f). *P  0.05, **P  0.01; NS, not significant.",
    "ncbi_link": "Atg5: 11793
Kras: 16653"
  },
  {
    "caption": "a, Kaplan-Meier analysis comparing PDAC-free survival in Atg7+/+ (blue) or Atg7−/− (red) KrasG12D/+ p53−/− mice.",
    "ncbi_link": "Atg7: 74244
Kras: 16653
p53: 22059"
  },
  {
    "caption": "e, Kaplan-Meier analysis comparing PDAC-free survival of Atg5+/+ (blue) or Atg5−/− (green) KrasG12D/+ p53−/− mice.",
    "ncbi_link": "Atg5: 11793
Kras: 16653
p53: 22059"
  },
  {
    "caption": "f, Kaplan-Meier analysis comparing PDAC-free survival of KrasG12D/+ p53−/− mice that were chloroquine-treated (CQ, red), vehicle-treated (PBS, black) or untreated (blue). a, e, f, The blue curve in all Kaplan-Meier plots represents the same colony of mice (KrasG12D/+, p53−/−, Atg7+/+, Atg5+/+). A Mantel-Cox test was used for statistics. b, d, Scale bars: 100 µm (b), 200 µm (d). *P 0.05, **P 0.01.",
    "ncbi_link": "Atg5: 11793
Atg7: 74244
Kras: 16653
p53: 22059"
  },
  {
    "caption": "b, Western blotting for LC3, p53 and Atg7 in cell lines derived from individual tumours which developed in the absence or presence of p53.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "c, d, Average oxygen consumption rate (OCR, c) and extracellular acidification rate (ECAR, d) of eight Atg7+/+ and seven Atg7−/− cell lines revealed increased ECAR in autophagy-deficient cells. Error bars are s.e.m.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "e, Treatment with 2-deocyglucose (2-DG) reduces ECAR and abrogates the difference between cell lines from Atg7+/+ and Atg7−/− tumours. Values are the average of three biological replicates. Error bars are s.e.m.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": ", g, LC-MS analysis revealed increased glucose consumption from medium (f) and extracellular lactate accumulation (g) in Atg7-null cell lines. Values are the average of eight (Atg7+/+) and seven (Atg7−/−) biological replicates.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "h, LC-MS analysis shows increased accumulation of 2-DG and its metabolite 2-DG-6-phosphate in Atg7-deficient cell lines. Values are averages of five biological replicates for each genotype.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "i, Background levels of 18F-FDG uptake in brain and heart can be seen in sagittal and coronal views (middle and right panels, respectively) of wild-type Atg7 mice (top row). In contrast, intense 18F-FDG uptake is seen in pancreatic tumours of Atg7 deficient mice (bottom row).",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "j, LC-MS of intracellular glycolytic and pentose phosphate pathway intermediates shows enhanced accumulation in Atg7−/− tumour cell lines. Values are average of eight (Atg7+/+) and six (Atg7−/−) biological replicates. f-h, j, Error bars are s.e.m. a, f-h, j, A Mann-Whitney U-test was used to ascertain significance. *P  0.05, **P  0.01.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "Western blot analysis and quantitation of ERAD proteins in Sel1Lf/f and Sel1LAlb livers (n=4 per group, 3 independent repeats). Hsp90 loading controls for Western blot analysis.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "Volcano plot depicting transcriptomics data from the livers of 9-week-old Sel1Lf/f and Sel1LAlb mice (n=3 per group); dotted line marks p=0.05; black dots represent fold change>2.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "qPCR analyses of Fgf21 expression in 9-week-old livers (n=3-6 per group, 3 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Ribosomal L32: 
Fgf21: 56636"
  },
  {
    "caption": "Protein levels of Sel1L (left panel) and mRNA levels of Fgf21 (right panel) in primary mouse hepatocytes isolated from the tamoxifen-inducible Sel1L-knockout Sel1LERCre mice (2 independent repeats). Hsp90 , loading control for Western blot analysis. Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Ribosomal L32: 
Cre: 2777477
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "Acute loss-of-function model where 8-week-old Sel1Lf/f mice were injected i.v. with either AAV8-Cre or control AAV8-GFP: Western blot analysis of hepatic and control adipose Sel1L protein (n=3 per group); Hsp90 loading control for Western blot analysis.",
    "ncbi_link": "GFP: 
Cre: 2777477
Sel1L: 20338"
  },
  {
    "caption": "Acute loss-of-function model where 8-week-old Sel1Lf/f mice were injected i.v. with either AAV8-Cre or control AAV8-GFP: qPCR analysis of hepatic Fgf21 expression and ELISA analysis of serum Fgf21 (n=3 per group, 2 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "GFP: 
Ribosomal L32: 
Cre: 2777477
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "Heatmaps of top 15 significantly upregulated and downregulated genes in Fgf21 Tg livers and their expression levels in Sel1LAlb livers (n=3 per group).",
    "ncbi_link": "Fgf21 : 56636
Sel1L: 20338"
  },
  {
    "caption": "Scatter plot depicting the logarithmic fold-change (FC) for 16,402 genes in Sel1LAlb and Fgf21 transgenic (Tg) livers (n=3 per group); genes that are highly upregulated or downregulated in both datasets are marked in red and blue, respectively; genes that are upregulated unique to each data set (e.g. Derl3 for Sel1L-Hrd1 ERAD-deficient liver) are marked in green.",
    "ncbi_link": "Derl3: 70377
Fgf21: 56636
Sel1L: 20338
Hrd1: 74126"
  },
  {
    "caption": "Data from rescue experiments where 5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. with AAV8-shFgf21 or control AAV8-shLuc: qPCR analysis of Fgf21 mRNA 3 weeks after injection (n=4 per group). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Luc: 
Ribosomal L32: 
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "Data from rescue experiments where 5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. with AAV8-shFgf21 or control AAV8-shLuc: ELISA analysis of Fgf21 in serum (K) 3 weeks after injection (n=4 per group).",
    "ncbi_link": "Luc: 
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "Data from rescue experiments where 5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. with AAV8-shFgf21 or control AAV8-shLuc: Weight gain curve after injection (n=7 per group).",
    "ncbi_link": "Luc: 
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "qPCR analysis of p-Stat5-associated growth genes in the livers of 9-week-old mice (n=6 per group, 2 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Ribosomal L32: "
  },
  {
    "caption": "qPCR analysis of browning-related genes in iWAT (n=3-6 per group). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Ribosomal L32: "
  },
  {
    "caption": "Western blot analysis of Crebh, Crebh-N, Pparα and Xbp1s in whole cell lysates (A) and nuclear extracts (B) in WT and Sel1LAlb livers (n=3 per group, 3 independent repeats) with quantitation shown in (C). Hsp90 lamin, loading controls for Western blot analysis.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "qPCR analysis of Crebh, Ppara and Xbp1s in WT and Sel1LAlb livers (n=4-6 per group, 2 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Ribosomal L32: 
Crebh: 208677
Ppara: 19013
Sel1L: 20338
Xbp1s: 22433"
  },
  {
    "caption": "Western blot analysis of Crebh in acute Sel1L loss of function model as described in Figure 2F-G (n=3 per group). Hsp90 , loading controls for Western blot analysis.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "ChIP analysis of Crebh binding onto the Fgf21 promoter in the livers of 9-week-old mice, normalized first to 5% input group and then to no-antibody ChIP samples (n=3 pooled per group, 2 independent repeats).",
    "ncbi_link": "Fgf21: 56636"
  },
  {
    "caption": "Western blot analysis of SEL1L, HRD1 and CREBH proteins in human Hep3B hepatocytes upon CRISPR deletion of SEL1L with two different guides. , β-actin loading controls for Western blot analysis.",
    "ncbi_link": "CRISPR: 
SEL1L: 6400"
  },
  {
    "caption": "qPCR analysis of SEL1L, HRD1 and FGF21 (K) in human Hep3B hepatocytes upon CRISPR deletion of SEL1L with two different guides. Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "CRISPR: 
Ribosomal L32: 
FGF21: 26291
SEL1L: 6400
HRD1: 84447"
  },
  {
    "caption": "Western blot analysis of Crebh protein half-life in transfected WT and HRD1-/- HEK293T cells treated with cycloheximide (CHX) for indicated times. The decay of protein from one experiment is shown below. Hsp90, loading control for Western blot analysis.",
    "ncbi_link": "HRD1: 84447"
  },
  {
    "caption": "Western blot analysis and quantitation of Crebh in Crebh-transfected WT (B) and HRD1-/- (C) HEK293T cells pre-treated with the proteasomal inhibitor bortezomib (BTZ) or lysosomal inhibitor chloroquine (CHQ) for 2 hours and then with CHX for additional 1 hour (n=2 per group, 2 independent repeats). Hsp90, loading control for Western blot analysis.",
    "ncbi_link": "Crebh: 84699
HRD1: 84447"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. Western blot analysis of hepatic Sel1L and Crebh 5 weeks post injection (n=3 mice each, 2 independent repeats). Hsp90, loading control for Western blot analysis.",
    "ncbi_link": "Luc: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. qPCR analysis of Crebh and Fgf21 mRNA 5 weeks post injection (n=3 per group, 2 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Luc: 
Ribosomal L32: 
Crebh: 208677
Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. ELISA analysis of circulating Fgf21 (C) 5 weeks post injection (n=3 per group, 2 independent repeats).",
    "ncbi_link": "Luc: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. qPCR analysis of hepatic growth-associated genes 5 weeks after injection (n=6 per group). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Luc: 
Ribosomal L32: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. Weight gain 6 weeks post injection (n=10 per group).",
    "ncbi_link": "Luc: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. Insulin tolerance test (ITT) 5-weeks after injection (n=10 per group).",
    "ncbi_link": "Luc: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. qPCR of Ucp1 levels in inguinal white adipose tissue (iWAT) 5 weeks post injection (n=3 per group, 2 independent repeats). Ribosomal L32, loading control for qPCR analysis.",
    "ncbi_link": "Luc: 
Ribosomal L32: 
Crebh: 208677
Sel1L: 20338
Ucp1: 22227"
  },
  {
    "caption": "5-week-old Sel1Lf/f and Sel1LAlb mice were injected i.v. once with AAV8-shCrebh or control AAV8-shLuc. Western blot analysis (H) of Ucp1 levels in inguinal white adipose tissue (iWAT) 5 weeks post injection (n=3 per group, 2 independent repeats). Hsp90, loading control for Western blot analysis.",
    "ncbi_link": "Luc: 
Crebh: 208677
Sel1L: 20338"
  },
  {
    "caption": "Analysis of correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 during fasting-feeding Western blot analysis of hepatic Sel1L-Hrd1 ERAD and Crebh of nuclear (Nuc) and cytosolic (Cyto) fractions from 10-week-old Sel1Lf/f and Sel1LAlb mice under overnight fasted or fed states.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "Analysis of correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 during fasting-feeding Quantitation of levels of Sel1L/Hrd1/Crebh proteins and Fgf21 mRNA in the livers of 10-week-old Sel1Lf/f mice.",
    "ncbi_link": "Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "during fasting-feeding Quantitation of total Crebh (Crebh+Crebh-N) protein levels in the livers of 10-week-old Sel1Lf/f and Sel1LAlb mice.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "during fasting-feeding Serum Fgf21 levels in 10-week-old Sel1Lf/f and Sel1LAlb mice.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "Analysis of correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 during growth Western blot analysis of hepatic Sel1L-Hrd1 ERAD and Crebh of nuclear (Nuc) and cytosolic (Cyto) fractions from the livers from Sel1Lf/f and Sel1LAlb mice at 3, 9 and 24 weeks of age.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "Analysis of correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 during growth Quantitation of levels of Sel1L/Hrd1/Crebh proteins and Fgf21 mRNA with the livers from Sel1Lf/f and Sel1LAlb mice at 3, 9 and 24 weeks of age.",
    "ncbi_link": "Fgf21: 56636
Sel1L: 20338"
  },
  {
    "caption": "Quantitation of total Crebh (Crebh+Crebh-N) protein levels in the livers from Sel1Lf/f and Sel1LAlb mice at 3, 9 and 24 weeks of age.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "Serum Fgf21 levels in the livers from Sel1Lf/f and Sel1LAlb mice at 3, 9 and 24 weeks of age.",
    "ncbi_link": "Sel1L: 20338"
  },
  {
    "caption": "B, C, D. WT, ∆cpt1∆ept1 (B), Δcho2 (C) or Δopi3 (D) cells expressing GFP-Atg8 were grown to logarithmic phase in SD-URA, and shifted to SD-N for 4 h of starvation. Cells were harvested at indicated time points and subjected to western blotting (left panel). Pgk1 was used as a loading control. Middle panel- Autophagic activity during starvation was quantified by calculating the ratio of free GFP to total GFP (GFP-Atg8 + free GFP). Statistical analysis was done by student's t-test (paired, two tailed) (ns- not significant, ****, p≤0.0001), error bars represent SEM of at least 3 independent experiments. Right panel- Ape1 maturation was quantified by measuring the mApe1 level out of the total Ape1 amount, during SD and SD-N.",
    "ncbi_link": "cho2: 853061
cpt1: 855593
ept1: 856523
opi3: 853536"
  },
  {
    "caption": "E. WT, Δopi3, and Δcho2 as well as Δatg1 (negative autophagy control) cells expressing chromosomally-tagged Fba1-GFP were grown to log phase in SD, and starved in SD-N for 4 hours. Cells were harvested at indicated starvation time points and subjected to western blotting (left panel). Pgk1 was monitored as a loading control. Right panel- Autophagic activity during starvation was quantified, by calculating the ratio of free GFP to total GFP (Fba1-GFP + free GFP).",
    "ncbi_link": "atg1: 852695
cho2: 853061
opi3: 853536"
  },
  {
    "caption": "F. WT, Δopi3, Δcho2 and Δatg1 cells on the background of pho8Δ60 pho13Δ strain, were grown to log phase in SD, and starved in SD-N for 4 hours. Pho8 activity was measured by the alkaline phosphatase assay.",
    "ncbi_link": "atg1: 852695
cho2: 853061
opi3: 853536
pho13: 851362
pho8: 852092"
  },
  {
    "caption": "A. Representative images of GFP-Atg8 (green) and vacuole (red, stained with FM4-64). WT, Δopi3 and Δcho2 cells expressing GFP-Atg8 were grown to log phase in SD-URA medium and shifted to SD-N for 3 h. Cells were observed by confocal microscopy before (SD) and during nitrogen starvation (SD-N) (left panel). Scale bar 1 µm. Right panel- Quantification of of cells with or without GFP inside vacuoles. Statistical analysis was done by Anova multiple comparisons test- Sidak's, compared to WT (****, p≤0.0001) (ns- not significant), error bars represent SEM of at least 3 independent experiments. Number of cells analyzed for each strain and condition: SD (WT (n=446), Δcho2 (n=272), Δopi3 (n=272)), SD-N (WT (n=398), Δcho2 (n=224), Δopi3 (n=213)).",
    "ncbi_link": "cho2: 853061
opi3: 853536"
  },
  {
    "caption": "A, B. WT and Δopi3 cells expressing GFP-Atg8 were grown to log phase in SD-URA, and shifted to SD-N for 4 h, choline (1 mM) was not supplemented (-choline) or supplemented to SD and SD-N (+choline SD, SD-N) or only to SD-N (+choline, SD-N) as indicated. Cells were harvested at indicated time points and subjected to western blotting (left panel). Pgk1 was monitored as a loading control. Middle panel- Autophagic activity was quantified during starvation by calculating the ratio of free GFP to total GFP (GFP-Atg8 + free GFP). Statistical analysis was done by Anova multiple comparisons test- Sidak's, compared to WT (ns-not significant, ****, p≤0.0001), error bars represent SEM of at least 3 independent experiments. Right panel- Ape1 maturation was quantified by measuring the mApe1 level out of the total Ape1 amount in Δopi3 cells at growth (SD) or during starvation (SD-N), with choline supplemented as indicated. Statistical analysis was done by Sidak's multiple comparisons test compared to WT (ns-not significant, *, p≤0.05, **, p≤0.005, ****, p≤0.0001), error bars represent SEM of at least 3 independent experiments.",
    "ncbi_link": "opi3: 853536"
  },
  {
    "caption": "C. Representative images of GFP-Atg8 (green) and vacuole (red, stained with FM4-64). WT and Δopi3 cells expressing GFP-Atg8 were grown in SD-URA and shifted to SD-N. Choline (1mM) was either excluded (-choline), added to growth and starvation medium (+choline SD, SD-N) or added only to starvation medium (+choline, SD-N). Cells were observed using confocal microscopy during starvation (left panel). Scale bar 1 µm. Right panel- Quantification of cells with GFP inside vacuoles. Statistical analysis was done by Anova multiple comparisons test- Sidak's, compared to WT (****, p≤0.0001, ns- not significant), error bars represent SEM of 3 independent experiments. Number of cells analyzed for each strain condition; -Choline: WT (n=487), Δopi3 (n=316), Choline SD, SD-N: WT (n=251), Δopi3 (n=361), Choline SD-N: WT (n=320), Δopi3 (n=267). D. PC levels determined by shotgun lipidomics for WT and Δopi3 cells expressing GFP-Atg8, with or without choline (1 mM) supplementation to SD-N. Samples were taken after 4 h in SD-N medium.",
    "ncbi_link": "opi3: 853536"
  },
  {
    "caption": "A. Representative Images of Atg5-mNG with sfTq2-Atg8 during SD-N. Δatg3 and Δatg3Δopi3 cells were grown to log phase in SD medium, shifted to SD-N for 4 h, and observed by Widefield microscopy (left panel), scale bar 1 µm. Right panel- quantification of percentage of cells with Atg5 puncta during different time points. Statistical analysis was done by Anova multiple comparisons test- Sidak's ns- not significant), error bars represent SEM of 2 independent experiments. Number of cells analyzed for each strain and time point (0 hour: Δatg3 (n=296), Δatg3Δopi3 (n=111), 1 hour: Δatg3 (n=325), Δatg3Δopi3 (n=110), 2 hours: Δatg3 (n=338), Δatg3Δopi3 (n=135), 4 hours: Δatg3 (n=309), Δatg3Δopi3 (n=167).",
    "ncbi_link": "atg3: 855741
opi3: 853536"
  },
  {
    "caption": "C. Representative images of WT and Δopi3 cells expressing GFP-Atg8. Cells were grown to log phase in SD-URA medium, shifted to SD-N for 3 h and observed by Airyscan microscopy (left panel). White dashes indicate cell boundaries, yellow dashes indicate phagophores. For each cell - Magnification of yellow dashed area (top right), schematic representation (bottom right). Scale bar 1 µm. Right panel- quantification of the percentage of cells with cup shaped GFP-Atg8 structures imaged by Airyscan microscopy. Statistical analysis was done by student's t-test (unpaired) (** p≤0.05), error bars represent SEM of least 3 independent experiments. Number of cells analyzed for each strain, WT (n=45), Δopi3 (n=110).",
    "ncbi_link": "opi3: 853536"
  },
  {
    "caption": "D. Representative CLEM images of WT and Δopi3 cells expressing GFP-Atg8, grown to log phase in SD-URA medium and shifted to SD-N for 3h. Cells were harvested, deep frozen and processed for CLEM (left panel), V-vacuole. For Δopi3 cell - Magnification of yellow dashed area of GFP-Atg8 positive phagophore (top right), TEM image only (middle right), schematic representation of a phagophore (bottom right). Scale bar 1 µm. Right panel- quantification of the percentage of cells with cup shaped GFP-Atg8 positive cup shaped membrane structures imaged by CLEM. Statistical analysis was done by student's t-test (unpaired) (*** p≤0.005), error bars represent SEM of least 3 independent experiments. Number of cells analyzed for each strain, WT (n=20), Δopi3 (n=21).",
    "ncbi_link": "opi3: 853536"
  },
  {
    "caption": "A. Representative images of Δypt7, Δopi3Δypt7 expressing GFP-Atg8 (z-stack projection). Cells were grown to log phase in SD-URA medium and starved in SD-N, images were taken during starvation in indicated time points by widefield microscopy (left panel). Scale bar 1 µm. Right panel- quantification of GFP-Atg8 puncta per cell in Δypt7, Δopi3Δypt7 at indicated time points. Statistical analysis was done by Anova multiple comparisons test- Sidak's (****, p≤0.0001, ns- not significant), compared to WT. Error bars represent SEM of least 3 independent experiments. Number of cells analyzed for each strain and time point, 0 hours: Δypt7 (n=322), Δopi3Δypt7 (n=194), 1.5 hours: Δypt7 (n=220), Δopi3Δypt7 (n=155), 3.5 hours Δypt7 (n=216), Δopi3Δypt7 (n=307). B. Quantification of cup-shaped phagophores in Δypt7 and Δopi3Δypt7 cells expressing GFP-Atg8 during starvation (1-3h). Statistical analysis was done by students t-test (***, p≤0.001), error bars represent SEM from at least 3 independent experiments. Number of cells analyzed for each strain, Δypt7 (n= 347), Δopi3Δypt7 (n= 474).",
    "ncbi_link": "opi3: 853536
ypt7: 855012"
  },
  {
    "caption": "C. Representative images of mNG-tagged Atg8 colocalized with mScarletI-PXVam7. WT, Δopi3, Δatg1 and Δopi3Δatg1 cells on the background of Δymr1, expressing mScarletI-PXVam7 under the CUP1 promoter from the knocked-out VPS38 locus, were grown to log phase in SD medium in the presence of 10 µM copper sulfate, and shifted to SD-N in the presence of 10 µM copper sulfate. Images were taken during SD-N (1-3 h) by widefield microscopy. D. Quantification of autophagic structure diameters in WT and Δopi3 cells on the background of Δymr1Δvps38 (C) by ImageJ. Statistical analysis was done by student's t-test, unpaired, two sided (ns- not significant), error bars represent SEM of at least three independent experiments. Number of cells analyzed for each strain, WT (n=51), Δopi3 (n=28).",
    "ncbi_link": "atg1: 852695
CUP1: 856450
opi3: 853536
VPS38: 851074
vps38: 851074
ymr1: 853574"
  },
  {
    "caption": "E. Representative images of Δypt7, Δopi3Δypt7 cells expressing GFP-Atg8 (projection). Cells were grown to log phase in SD-URA medium and starved in SD-N, with supplementation of choline (1 mM) to SD and SD-N as indicated. Images were taken during growth and starvation by confocal microscopy (left panel). Scale bar 1 µm. Right panel- quantification of cell with more than two GFP-Atg8 puncta, in Δypt7 and Δopi3Δypt7 at growth (SD) or starvation (SD-N) in the presence (+choline: SD, SD-N) or absence (-choline) of choline (1 mM). Incidence were normalized to Δypt7 (SD-N) control. Statistical analysis was done by Anova multiple comparisons test- Sidak's (***, p≤0.001). Error bars represent SEM of least 3 independent experiments. Number of cells analyzed for each strain and condition, SD: Δypt7 (n=209), Δopi3Δypt7 (n=111), SD-N: Δypt7 (n=118), Δopi3Δypt7 (n=103), SD+Choline: Δypt7 (n=107), Δopi3Δypt7 (n=120), Δypt7 (n=84), Δopi3Δypt7 (n=74).",
    "ncbi_link": "opi3: 853536
ypt7: 855012"
  },
  {
    "caption": "Indirect immunofluorescence analysis of mAtg9 with (D)HA-full‐length p38IP (HA-FL), (E)HA-C‐terminal p38IP (HA-CT), and (F) HA-N‐terminal p38IP (HA-NT). Bars=5 μm. The co‐localization seen in (D) and (E) was not because of overlap of randomly distributed vesicles. Cross‐correlation function (CCF) analysis ( van Steensel et al, 1996) showed a peak and maximum Rp value around ΔX=0, indicating that co‐localization between mAtg9 and p38IP is positively correlated and non random ( Supplementary Figure S1).",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(A) HEK293A cells were transfected with HA-p38IP alone or co‐transfected with HA-p38IP and RFP-mAtg9, homogenized and subjected to centrifugation, and the resulting post‐nuclear supernatant (PNS) was fractionated by centrifugation at 100 000 g into membrane pellet and cytosol. Equal protein amounts were resolved by SDS-PAGE and immunoblotted with anti‐mannose‐6‐phosphate receptor (MPR) antibody as a control for membrane‐associated proteins, anti‐superoxide dismutase (SOD) antibody as a control for cytosolic proteins, anti‐mAtg9 antibody, and anti‐HA antibody. HA-p38IP levels were quantified using ImageJ software and plotted relative to HA-p38IP in the PNS (n=4) (**P=0.0051).",
    "ncbi_link": "Atg9: 285973///79065
p38IP: 55578"
  },
  {
    "caption": "(B) HEK293 cells were depleted of mAtg9 using siRNA, then transfected with HA-p38IP and incubated in full medium or EBSS (data not shown). The asterisk indicates mAtg9‐depleted cells. Bar is 5 μM. The intensity of the nuclear versus cytosolic fluorescence in control and cells depleted of mAtg9 under fed and starvation conditions was analysed using ImageJ software (***P=0.0001, Students t‐test)",
    "ncbi_link": "Atg9: 285973///79065
p38IP: 55578"
  },
  {
    "caption": "(C) HEK293A cells were transfected with HA-p38IP and processed for indirect immunofluorescence. HA-p38IP was detected with an anti‐HA antibody and endogenous mAtg9 was detected with an anti‐mAtg9 antibody. HA-p38IP localizes to the nucleus and cytoplasmic puncta in full medium or EBSS. HA-p38IP co‐localizes with mAtg9 in the periphery of the cell (arrowheads). Bars (upper panels) 5 μM, (lower panels) 1 μM.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(D) Anti‐mAtg9 antibody was used to immunoprecipitate mAtg9 from HEK293 cells transfected with HA-p38IP alone or with RFP-mAtg9 and HA-p38IP. A total of 5% of lysates or immunoprecipitates were probed with anti‐HA or anti‐mAtg9 antibodies. The left and right hand bottom panels were obtained from the same immunoblot, but exposed for different times to allow the endogenous mAtg9 to be visualized better.",
    "ncbi_link": "Atg9: 285973///79065"
  },
  {
    "caption": "(E) HEK293 cells were transfected with control or p38IP siRNA. At 72 h after transfection, cells were incubated in either full medium or EBSS for 2 h, then fixed and immunostained to detect endogenous mAtg9 localization. mAtg9 localization was quantified by visually scoring cells for either a juxta‐nuclear or dispersed phenotype. Bars=5 μm (data are represented as mean±s.e.m. of 200 cells, *P=0.0413, Student's t‐test).",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(A) 293/GFP-LC3 cells were transfected with control or p38IP siRNA. At 72 h after transfection, cells were incubated in either full medium (FM), full medium with leupeptin (FM Leu), EBSS (ES), or EBSS with leupeptin (ES Leu) for 2 h. FM Leu (data not shown) is identical to FM alone. Quantification of GFP-LC3‐positive autophagosome number was performed by counting in a blinded experiment. Bars=5 μm (data are represented as mean±s.e.m. of 60 cells, ***P=0.0002, Students t‐test).",
    "ncbi_link": "LC3: 440738///81631///84557
p38IP: 55578"
  },
  {
    "caption": "(B) HEK293A cells were transfected with siRNA control, siRNA for p38IP, and siRNA for ULK1. Cell lysates were analysed by SDS-PAGE for endogenous LC3 lipidation using an anti‐LC3 antibody, or immunoblotted with anti‐ULK1 antibody.",
    "ncbi_link": "p38IP: 55578
ULK1: 8408"
  },
  {
    "caption": "(C) HeLa cells were transfected with siRNA control, and siRNA for p38IP. After incubation for 2 h as in (A), samples were immunoblotted with anti‐LC3 and anti‐actin antibodies. Endogenous LC3II/LC3I levels were quantified and the ratio presented as arbitrary units. In (B), n=4, ***P=0.0001 and *P=0.0324, Students t‐test. In (C), data are representative of two experiments.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(D) 293/GFP-LC3 cells were transfected with siRNA control or siRNA p38IP, and incubated in full medium, or for 2 and 4 h in EBSS. Samples were immunoblotted with anti‐p62 antibodies, and actin as a loading control.",
    "ncbi_link": "LC3: 440738///81631///84557
p38IP: 55578"
  },
  {
    "caption": "(E) HEK293A cells were transfected with HA-p38IP or myc-ULK1 C‐terminal domain (CTD). After 24 h, cells were labelled with [14C]valine as described in Material and Methods section, and incubated in either full medium or EBSS for 2 h. Cells were then collected and analysed for long‐lived protein degradation (data are represented as mean±s.e.m. of triplicates, representative of two experiments, EBSS mock versus EBSS HA-p38IP (***P=0.036); EBSS mock versus ULK1 CTD (***P=0.0001); Students t‐test).",
    "ncbi_link": "p38IP: 55578
ULK1: 8408"
  },
  {
    "caption": "(A) 293/GFP-LC3 cells were treated with 10 μM anisomycin for 30 min, or exposed to UV irradiation for 3 min followed by a 40‐min recovery and incubation in full medium, full medium with leupeptin, EBSS, or EBSS with leupeptin for 2 h. Cells were then fixed and visualized by confocal microscopy. GFP-LC3‐positive structures per cell were quantified as in Figure 3A. Bars=5 μm. Data are represented as mean±s.e.m. n=60 cells, mock versus anisomycin EBSS (***P=0.0001); mock versus UV EBSS (***P=0.0001); mock versus anisomycin EBSS with leupeptin (***P=0.0001); mock versus EBSS with leupeptin UV (***P=0.0001). All analysed using Student's t-test.",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(A) 293/GFP-LC3 cells were pre‐treated with 10 μM anisomycin for 30 min before incubation in either full medium or EBSS. Cell lysates were analysed by SDS-PAGE for GFP-LC3 lipidation using an anti‐LC3 antibody. The membrane was also probed with anti‐β tubulin. The GFP-LC3 lipidation was quantified as the amount of GFP-LC3II/GFP-LC3I (data are represented as mean±s.e.m. of triplicates, P=0.0091, Student's t‐test).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) HEK293 cells were transfected with control siRNA or siRNA for p38IP. After 24‐h incubation, control or p38IP‐depleted cells were pre‐treated with anisomycin, followed by a 2‐h incubation with full medium, full medium with leupeptin, EBSS, or EBSS with leupeptin. Cell lysates were analysed with anti‐p38α or anti‐LC3 antibodies. LC3II/LC3I levels were quantified and presented normalized to control, untreated cells incubated in EBSS. Data are representative of two experiments.",
    "ncbi_link": "p38IP: 55578"
  },
  {
    "caption": "(D) HEK293A cells transiently transfected with HA‐p38IP and RFP‐mAtg9 were treated with anisomycin for 30 min and mAtg9 was immunoprecipitated. 5% of the lysates or the immunoprecipitates were probed with anti‐HA and anti‐mAtg9 antibodies (data is representative of 3 experiments, *P=0.0332).",
    "ncbi_link": "Atg9: 285973///79065
p38IP: 55578"
  },
  {
    "caption": "(A) HEK293A cells were transfected with RFP-mAtg9 and Flag-p38 (lanes 2 and 7), RFP-mAtg9, Flag-p38 and HA-p38IP (lanes 3 and 8), or RFP-mAtg9 and HA-p38IP (lanes 4 and 9). RFP-mAtg9 was immunoprecipitated with an anti‐mAtg9 antibody, the co‐immunoprecipitated HA-p38IP was detected with an anti‐HA antibody, and co‐immunoprecipitated Flag-p38 was detected with an anti‐Flag antibody. RFP-mAtg9 was detected with an anti‐Atg9 antibody.",
    "ncbi_link": "Atg9: 285973///79065
p38: 1432///5603///6300///5600
p38IP: 55578"
  },
  {
    "caption": "(C) HEK293A cells were transfected with Flag-p38α for 24 h. Cells were incubated in either full medium, EBSS, or EBSS plus leupeptin for 2 h, lysed, and analysed for endogenous LC3 lipidation using an anti‐LC3 antibody, and immunoblotted with anti‐Flag antibody. LC3 lipidation was quantified as the amount of LC3II/LC3I (data are represented as mean±s.e.m. of triplicates, n=2 experiments, EBSS control versus EBSS with Flag‐p38α, ***P=0.0026).",
    "ncbi_link": "p38α: 1432"
  },
  {
    "caption": "(A) 293/GFP-LC3 cells were transfected with control or p38α siRNA. At 72 h after transfection, cells were incubated in either full medium, EBSS, or EBSS with leupeptin for 2 h, then fixed and visualized by confocal microscopy. Bars=5 μm (data are represented as mean±s.e.m. n=60 cells, EBSS control versus p38α siRNA (***P=0.0001); EBSS with leupeptin control versus p38α siRNA (***P=0.0001), Student's t‐test).",
    "ncbi_link": "LC3: 440738///81631///84557
p38α: 5594"
  },
  {
    "caption": "(B) HEK293A cells were transfected with control or p38α siRNA. At 72 h after transfection, cells were incubated in either full medium, EBSS, or EBSS containing leupeptin for 2 h. Cells lysates were analysed for LC3 lipidation using an anti‐LC3 antibody. The membrane was also probed with anti‐actin and anti‐p38α antibodies. LC3 lipidation was quantified as the amount of LC3II/LC3I (data are represented as mean ±s.e.m. n=5, full medium control versus p38α siRNA (**P=0.0056); EBSS control versus p38α siRNA (**P=0.048); EBSS with Leu control versus p38α siRNA (**P=0.04), Student's t‐test).",
    "ncbi_link": "p38α: 1432"
  },
  {
    "caption": "(C) HEK293A cells were transfected with control or p38α siRNA. At 72 h after transfection, cells were incubated in either full medium or EBSS for 2 h, then fixed and immunostained to detect endogenous mAtg9 localization. The percentage of cells with dispersed mAtg9 was quantified as in Figure 2E (data are represented as mean±s.e.m. n=200 cells, full medium control versus p38α siRNA (**P=0.0027); EBSS control versus p38α siRNA (*P=0.0459); Student's t‐test). Bars=5 μm",
    "ncbi_link": "p38α: 1432"
  },
  {
    "caption": "(D) HEK293A cells were transfected with siRNA for p38α, homogenized and subjected to centrifugation, and the resulting post‐nuclear supernatant (PNS) was fractionated by centrifugation at 100 000 g into membrane pellet and cytosol as in Figure 2A. Equal protein amounts were resolved by SDS-PAGE and immunoblotted with anti‐MPR, anti‐HA, and anti‐p38α antibodies. Data are representative of four experiments.",
    "ncbi_link": "p38α: 1432"
  },
  {
    "caption": "(E) 72 h cells were transfected with control, p38α siRNA or both p38α siRNA, and p38IP siRNA. At 72 h after transfection, cells were incubated in either full medium, full medium with leupeptin, EBSS, or EBSS with leupeptin for 2 h. Cells lysates were analysed for LC3 lipidation using an anti‐LC3 antibody. The membrane was also probed with anti‐p38α. LC3 lipidation was quantified as the amount of LC3II/LC3I. Data are representative of two experiments.",
    "ncbi_link": "p38α: 1432
p38IP: 55578"
  },
  {
    "caption": "High power single plane confocal  images of EdU  labeled control and TRIM71-expressing organoids. An EdU  pulse was given on day 8 and  EdU incorporation  (green) was analyzed 1.5 hours later. JAG1 immunostaining  (magenta) marks supporting cells/prosensory cells, mCherry  (red) marks transduced cells, Hoechst  labels cell nuclei  (blue). Scale bar= 25µm. Percentage of EdU+ mCherry+ cells per organoids in (I); (n = 5, two independent experiments). P-values were calculated using two-tailed, unpaired t test. **P < 0.01. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ±standard deviation (SD) of biological replicates.",
    "ncbi_link": "TRIM71: 131405"
  },
  {
    "caption": "RT-qPCR  of Atoh1  mRNA in organoids (n=3, two independent experiments). P-values were calculated using one-way ANOVA with Tukey's correction. ****P < 0.0001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Atoh1: 11921"
  },
  {
    "caption": "RT-PCR  of Myo7a  mRNA expression in organoids (n=3, two independent experiments). P-values were calculated using one-way ANOVA with Tukey's correction. *P ≤ 0.05. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Myo7a: 17921"
  },
  {
    "caption": "Colony forming efficiency  (n=4 in WT, n=5 in Trim71  KO, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. n.s, not significant. Organoid  diameter (n=4 in WT, n=5 in Trim71  KO, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. n.s, not significant. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "High power single plane confocal  images of EdU  (red) and Hoechst  (blue) labeled WT and TRIM71  KO organoids. A single EdU  pulse was given on day 7 and  EdU incorporation was analyzed 1.5 hours later. Scale bars = 25µm. Percentage of EdU+ cells in (F) (n=15 in WT, n=11 in Trim71  KO, three independent experiments). Two-tailed, unpaired t test was used to calculate P values, n.s. not significant. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Trim71: 636931
TRIM71: 636931"
  },
  {
    "caption": "RT-qPCR of Trim71  and  hair cell-specific (Atoh1, Gfi1  and Pou4f3) mRNAs in WT and Trim71  KO organoids after 2 days of differentiation (n=3, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. *P < 0.05. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Atoh1: 11921
Gfi1: 14581
Pou4f3: 18998
Trim71: 636931"
  },
  {
    "caption": "Cochlear epithelial cells  isolated from P5 wild type mice  were transduced with control (Ctrl) or TRIM71-expressing lentivirus  and bulk RNA sequencing was used to analyze differential  gene expression  after 10 days of expansion. Volcano plot of RNA-seq  data. Plotted is beta-value (x-axis) versus −log10 q-value (y-axis). Transcripts that are significantly upregulated in response to TRIM71  expression are marked in red circles, and transcripts that are significantly downregulated are marked in blue circles.",
    "ncbi_link": "TRIM71: 131405"
  },
  {
    "caption": "Immunoblots  showing LIN28B, AGO2, HMGA2, P-SMAD1/5/9 and β-actin protein levels in P5 control, TRIM71  and △NHL expressing cochlear  organoids at 10 days of expansion. Note β-actin was used to normalize protein levels.",
    "ncbi_link": "TRIM71: 131405"
  },
  {
    "caption": "Cochlear epithelial cells  isolated from P5 wild type were transduced with control (Ctrl) or TRIM71-expressing lentivirus  and expanded as organoids. MCherry (red) marks transduced cells. Hoechst staining  (blue) labels cell nuclei. High power single plane confocal images of control (Ctrl) and TRIM71-expressing organoids immuno-stained  for progenitor/supporting cell marker JAG1  (magenta) and progenitor  marker HMGA2  (green) after 10 days of expansion. Scale bars=25µm. Quantification of JAG1+ mCherry+ HMGA2+ cells per organoid in (A) (n=3, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. ***P < 0.001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "TRIM71: 131405"
  },
  {
    "caption": "Cochlear epithelial cells  isolated from P5 wild type were transduced with control (Ctrl) or TRIM71-expressing lentivirus  and expanded as organoids. MCherry  (red) marks transduced cells. Hoechst staining  (blue) labels cell nuclei. High power confocal   images of control (Ctrl) or TRIM71-expressing organoids immuno-stained  for progenitor/supporting cell marker JAG1  (magenta) and supporting cell  marker S100A1  (green) after 10 days of expansion. Scale bars=25µm. Quantification of JAG1+ mCherry+ S100A1+ cells per organoid in (C) (n=3, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. **P < 0.01. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "TRIM71: 131405"
  },
  {
    "caption": "Cochlear epithelial cells isolated from Atoh1-nGFP  transgenic mice  (E, F) were transduced with control (Ctrl) or TRIM71-expressing lentivirus  and expanded as organoids. MCherry  (red) marks transduced cells. Hoechst staining  (blue) labels  cell nuclei. High power single plane confocal  images of control (Ctrl) or TRIM71-expressing organoids immuno-stained  for transcription factor NFIB  (magenta) after 2 days of differentiation. Atoh1-nGFP  (green) marks nascent hair cells. White arrowheads mark Atoh1-GFP+ cells with low NFIB  expression (NFIBlow). Scale bars=25µm. Quantification of NFIBlow, NFIBhigh, NFIBlowAtoh1-nGFP+, NFIBhigh Atoh1-nGFP+ cells in control (Ctrl) and TRIM71-expressing organoids (n=4, two independent experiments). Two-way ANOVA with Tukey's correction was used to calculate P values. ****P < 0.0001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "nGFP: 
Atoh1: 11921
TRIM71: 131405"
  },
  {
    "caption": "Percentage of mCherry+Atoh1-nGFP+ organoids  in (B) (n=5 for Lin28b  group, n=6 for all the other groups; two independent experiments). One-way ANOVA with Tukey's correction was used to calculate P values. *P ≤ 0.05, **P < 0.01 and ****P < 0.0001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Lin28b: 380669"
  },
  {
    "caption": "RT-qPCR- analysis of progenitor   (Hmga2) and supporting cell-specific (Zbtb20, Nfib) gene expression in control, Lin28b, TRIM71  or Lin28b+TRIM71-expressing organoids after 10 days of expansion (n=3, two independent experiments). One-way ANOVA with Tukey's correction was used to calculate P values. *P ≤ 0.05, **P < 0.01 and ***P < 0.001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates.",
    "ncbi_link": "Hmga2: 15364
Lin28b: 380669
Nfib: 18028
TRIM71: 131405
Zbtb20: 56490"
  },
  {
    "caption": "RT-qPCR analysis of  hair cell  (Aoth1  and Pou4f3) and progenitor-specific (Trim71) gene expression in Hmga2  knockdown and control cultures. Hmga2  expression was analyzed to confirm knockdown. Plotted are fold difference between control and Hmga2  shRNA group and mean ± SD (n=3, biological replicates; two independent experiments). A two-tailed, unpaired t test was used to calculate P values. **P < 0.01, ***P < 0.001 and ****P < 0.0001. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates. ",
    "ncbi_link": "Aoth1: 11921
Hmga2: 15364
Pou4f3: 18998
Trim71: 636931"
  },
  {
    "caption": "Low power  bright field (BF) and green fluorescent images (Atoh1-nGFP) of Hmga2  shRNA knockdown and control organoid  cultures after 2 days of differentiation. Scale bars=400 µm. Quantification of Atoh1-nGFP+ organoids  in (E) (n=3, two independent experiments). A two-tailed, unpaired t test was used to calculate P values. *P ≤ 0.05. Data information: Plotted are individual data points, representing the average value per animal and treatment, and mean ± SD of biological replicates. ",
    "ncbi_link": "Hmga2: 15364"
  },
  {
    "caption": "E Damage-induced translocation of UBE2QL1 to lysosomes. The three best candidates (from D) were transiently expressed with N-terminal HA-tag in HeLa cells. Cells were treated with LLOMe or EtOH (untreated) for 3 h, fixed and stained for HA and LAMP1 as indicated and imaged by confocal laser scanning microscopy. Scale bar: 10 µm. F Automated quantification of (E). Shown are Pearson correlation coefficients (P.C.C) of HA and LAMP1 signals. Graph represents data from three independent experiments with ≥ 30 cells per condition (mean ± SD). ****P<0.0001 (One-way-ANOVA with Bonferroni's multiple comparison test). ",
    "ncbi_link": "HA: "
  },
  {
    "caption": "G Western blot detection of endogenous UBE2QL1 and depletion efficiency. Cells were transfected with control siRNA (Ctrl), two UBE2QL1 siRNAs from the screen (#2 or #4) or an additional siRNA (#5), and lysates probed with an antibody to UBE2QL1 as indicated. GAPDH was probed as loading control.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "A HeLa cells were transfected with different UBE2QL1 siRNAs for 60 h, and LLOMe or control-treated (untreated) for 3 h. Cells were fixed and immuno-stained for LAMP1 along with antibodies specific for K63 or K48-linked ubiquitin chains as indicated and imaged with a laser scanning confocal microscope. Note the strong reduction of damage-induced K48 ubiquitination and decreased intensity of the K63 signal. Scale bar: 20 µm. B, C Automated image quantification of (A). Shown are percentages of K48 or K63-positive LAMP1 vesicles per cell. Graphs represent data from three independent experiments with ≥ 70 cells per condition (mean ± SD). **P<0.01; ***P<0.001; ****P<0.0001 (One-way-ANOVA with Bonferroni's multiple comparison test).",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "A HeLa cells expressing UBE2QL1-HA were fixed at indicated time points after LLOMe treatment and processed for confocal microscopy. Cells were stained with antibodies specific for LAMP1 (not shown), and combinations of HA with K48 chains, K63 chains or p62 as indicated. Note the delayed co-emergence of K48 chains and UBE2QL1 vesicles, compared to the earlier appearance of K63 chains and p62. Arrows indicate colocalizing or non-colocalizing vesicles. Scale bars: 10 µm, 2 µm for inlays. B Automated quantification of (A). Shown are the Pearson correlation coefficients (P.C.C.) representing colocalization of UBE2QL1-HA, K48 chains, K63 chains or p62 with LAMP1-positive vesicles. Graphs represent data from three independent experiments with ≥ 30 cells per condition (mean ± SD). C Automated quantification of (A). P.C.C.'s representing colocalization of K48 chains, K63 chains or p62 with UBE2QL1-HA in cells treated with LLOMe or vehicle alone (untreated) for 180 min. Graphs represent data from three independent experiments with ≥ 30 cells per condition (mean ± SD). ",
    "ncbi_link": "HA: 
UBE2QL1: 134111"
  },
  {
    "caption": "Immuno-electron microscopy of LLOMe-treated HeLa cells. Cells in (A) overexpress mCherry-Gal3 and a dominant-negative C160S mutant of GFP-YOD1, and were immunostained for p62 (A) p62 (10 nm gold particles) localizes as a cap (arrowheads) to the outer limiting membrane of lysosomes (L). Scale bars: 200 nm.",
    "ncbi_link": "GFP: 
mCherry: 
Gal3: 3958
YOD1: 55432"
  },
  {
    "caption": "Immuno-electron microscopy of LLOMe-treated HeLa cells. Cells in (B) overexpress mCherry-Gal3 and a dominant-negative C160S mutant of GFP-YOD1, and were immunostained for p62 and K48. (B) K48 ubiquitin chains (15 nm gold particles, arrows) are found in the lumen of lysosomes, that also contain p62 (10 nm gold particles, arrowheads) at their outer membrane. Scale bars: 200 nm.",
    "ncbi_link": "GFP: 
mCherry: 
Gal3: 3958
YOD1: 55432"
  },
  {
    "caption": "Immuno-electron microscopy of LLOMe-treated HeLa cells. (C) Overexpressed UBE2QL1-GFP (10 nm gold particles) is found in late endosomes (LE, Inset) and lysosomes. M = mitochondrion. Scale bars: 200 nm.",
    "ncbi_link": "GFP: 
UBE2QL1: 134111"
  },
  {
    "caption": "D, E Comparative UBE2QL1 proximity mapping before and after lysosome damage using SILAC mass spectrometry. HeLa cells expressing a UBE2QL1-APEX2 fusion were EtOH (light-labelled, L)- or LLOMe (heavy-labelled, H)-treated and pulsed with biotin phenol (30 min) and H2O2 (1 min). Proteins detected in replicative streptavidin purifications are depicted in a Venn diagram (D) and displayed high correlation coefficients (E).",
    "ncbi_link": "APEX2: 27301
UBE2QL1: 134111"
  },
  {
    "caption": ", F Comparative UBE2QL1 proximity mapping before and after lysosome damage using SILAC mass spectrometry. HeLa cells expressing a UBE2QL1-APEX2 fusion were EtOH (light-labelled, L)- or LLOMe (heavy-labelled, H)-treated and pulsed with biotin phenol (30 min) and H2O2 (1 min). (F) Results from the four experiments are summarized in a volcano plot. Horizontal dotted line represents the significance threshold (p > 0.05). The vertical lines indicate the fold change cutoff (log2 (H/L) ≥ 1.5). Red dots indicate proteins above the significance and fold-change thresholds. Protein names are color-coded in blue (endosome/lysosome-associated), green (endolysosomal damage/autophagy-associated) and orange (VCP/p97 and its cofactors).",
    "ncbi_link": "APEX2: 27301
UBE2QL1: 134111"
  },
  {
    "caption": "A HeLa cells stably expressing p97-GFP were control or UBE2QL1-depleted for 48 h and expression of p97-GFP was induced for the last 24 h. Cells were LLOMe or control treated for 1 h, fixed after a chase of 2 h, and stained with antibodies to K48 ubiquitin chains and LAMP1 as indicated. Note the reduction of the K48 and p97-GFP signals on damaged lysosomes in UBE2QL1-depleted cells. Arrows indicate colocalizing or non-colocalizing vesicles. Scale bars: 20 µm, 10 µm for inlays.",
    "ncbi_link": "GFP: 
UBE2QL1: 134111
p97: 116643"
  },
  {
    "caption": "C HeLa cells were control or UBE2QL1-depleted for 60 h, fixed after 1 h of LLOMe or control treatment and stained for LAMP1 and p62 and analyzed by confocal microscopy. Arrows indicate colocalizing or non-colocalizing vesicles. Scale bars: 20 µm, 5 µm for inlays.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "G Western blot analysis of lysates of cells transfected with UBE2QL1 or control siRNA for 72 h, treated with 200 nM Bafilomycin A1 for 5 h or 250 µM LLOMe for 3 h as indicated and probed with an antibody specific for LC3A/B. GAPDH was probed as loading control.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "A Gal3 puncta assay for damaged lysosomes. HeLa cells were depleted of UBE2QL1 with two siRNAs for 60 h and treated with LLOMe or EtOH alone (untreated) for 1 h. Cells were fixed at indicated times after washout, stained with DAPI and Gal3 and LAMP1 antibodies, and processed for confocal microscopy. Note increased number of Gal3 puncta in untreated UBE2QL1-depleted cells and their persistence 10 h after LLOMe-induced damage. Scale bars: 10 µm, 2 µm for inlays. Arrows indicate Gal3 and LAMP1 colocalizing vesicles.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "C Survival assay. Control or UBE2QL1-depleted HeLa cells (48 h) were treated with increasing concentrations of LLOMe as indicated. Cell viability was measured with the MTS assay. Graph represents data from one experiment including three replicates (mean ± SD). *P<0.05; ****P<0.0001 (One-way-ANOVA with Bonferroni's multiple comparison test).",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "A Control or UBE2QL1-depleted (for 60 h) HeLa cells were stained with DAPI and an antibody against TFEB and automatically analyzed by confocal microscopy. Note nuclear translocation of TFEB upon loss of UBE2QL1. Scale bar: 20µm.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "C Cells were stained for LAMP1 and mTOR. Note the increase in lysosomes and lysosomal dissociation of mTOR in UBE2QL1 depleted cells. Scale bar: 20 µm.",
    "ncbi_link": "UBE2QL1: 134111"
  },
  {
    "caption": "G C.elegans wild-type (N2) and mutant strains for ubc-25(ok1732), for scav-3(qx193) or the ubc-25 and scav-3 double mutant (ok1732;qx193) carrying a EGFP-Gal3 transgene were imaged in adult worms (L4 + 24 h). 3D reconstructions of the hypodermis. Small and big units represent 1 and 5 µm, respectively.",
    "ncbi_link": "EGFP: 
Gal3: 3958
scav-3: 176673
ubc-25: 172941"
  },
  {
    "caption": "(b) IRGMC mRNA was significantly enriched in miR-196B complexes. Extracts of cells expressing FLAG-tagged-AGO1 and transfected with biotinylated miR-196B or control miR-20 as indicated and then with IRGMC or IRGMT plasmids were submitted to tandem affinity purification (immunoprecipitation with FLAG antibodies followed by affinity purification on streptavidin beads). IRGM mRNA variants were quantified using quantitative RT-PCR; results are presented as the ratio between miR-196B and miR-20 (non-relevant miRNA) pull-downs and the mean of three independent experiments ± standard deviation (s.d.). IP strep, immunoprecipitation straptavidine.",
    "ncbi_link": "miR-20: 
IRGM: 345611
miR-196B: 442920"
  },
  {
    "caption": "(c) HEK293 cells (IRGMC/C) were transfected with either FLAG-tagged IRGMC or FLAG-tagged IRGMT plasmids and co-transfected with miR-196B. Immunoblotting with an IRGM antibody revealed the specificity of the downregulation effect mediated by the miRNA IRGM mRNA interaction. Quantification of the immunoblot signals are presented as IRGM expression relative to actin (mean of at least three independent experiments ± s.d.).",
    "ncbi_link": "IRGM: 345611
miR-196B: 442920"
  },
  {
    "caption": "(b) Epithelial or laminal fractions were captured from sections of biopsies of healthy controls (n = 8) or individuals with Crohn's disease with no inflammation (n = 16), quiescent (defined as low-grade inflammation) (n = 8) or acute inflammation (n = 8) using laser capture microdissection. After RNA extraction, miR-196A (black bars) and miR-196B (white bars) relative expression was analyzed using RNU19, 44 and U6. To overcome possible inter-individual bias, the lamina propria fraction value was used for relative quantification. Due to high differences in expression between healthy and inflamed tissues, the results are presented as a log2-fold ratio. Error bars indicate the s.d. of the ΔΔCt values.",
    "ncbi_link": "miR-196A: 406973///406972
miR-196B: 442920"
  },
  {
    "caption": "(c) Representative in situ staining for IRGM of TMAs from colon biopsies of healthy individuals or individuals with Crohn's disease with a defined genotype in a healthy non-inflamed or an acute inflamed phase. Scale bars, 32 μm. (d) Mean (black line), s.e.m. (white box) and 95% CI of the mean of the IRGM expression level for 40 healthy subjects (32 individuals with C/C and 8 individuals with C/T) and 67 individuals with Crohn's disease (45 with C/C and 22 with C/T) with quiescent or inflamed colon mucosa. We performed statistical analysis using ANOVA (P = 0.0015) and an unpaired Student's t-test (the one tail P value is indicated on the figure).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(a) The basal flux of autophagy is affected by IRGM expression level. HEK293 cells transfected with an IRGM-expressing plasmid, miR-196 or siIRGM were treated with bafilomycin A1 for 2 h and processed for immunoblotting with anti-LC3B. (b) Quantification of LC3-II relative to actin (mean of three independent experiments ± s.d.).",
    "ncbi_link": "IRGM: 345611
miR-196: 442920///406973///406972"
  },
  {
    "caption": "(c) Downregulation of IRGM expression by miR-196 abrogates AIEC-mediated autophagy in cells treated with autophagic inhibitors (Inh) or transfected with miR-196B and infected for 4 h with AIEC LF82 (mean of three independent experiments ± s.d.).",
    "ncbi_link": "miR-196B: 442920
miR-196: 442920///406973///406972"
  },
  {
    "caption": "(d) Confocal microscopic examination of LC3 revealed a significant decrease in the percentage of LC3-associated (red) LF82 bacteria (green) in miR-196 transfected cells compared to control cells (mean ± s.d.).",
    "ncbi_link": "miR-196: 442920///406973///406972"
  },
  {
    "caption": "(e) miR-196 transfection leads to increased intracellular LF82 replication. Results are expressed as a fold increase ± s.e.m. of intracellular bacteria.",
    "ncbi_link": "miR-196: 442920///406973///406972"
  },
  {
    "caption": "(f) IRGM overexpression did not inhibit autophagic flux and it increased LC3-II accumulation slightly in response to AIEC infection. HEK293 cells were transfected with IRGM-expressing plasmid, treated with autophagic inhibitors and infected with AIEC bacteria for 4 h (mean of three independent experiments ± s.d.).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(g) Confocal microscopic examination showed an increased percentage of LC3-associated AIEC bacteria in IRGM cells compared to control cells (mean ± s.d.). (h) IRGM overexpression led to a high rate of intracellular replication of LF82 bacteria. (i) Most of the bacteria reside in non-acidic vacuoles, as shown with lysotracker at 8 h post infection (means of three independent experiments ± s.d.).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "f, Representative Dot Blot of 100K EV pellet (each dot represents 3 pooled EV isolations, derived from 60*106 cells; N = 8 experiments) vs cell lysate (CL) from P8 Nrl.Gfp+/+ photoreceptors. EV markers = LAMP1, CD8, CD9; Golgi marker = GM130; phototransduction markers = Recoverin, Rhodopsin, Rod α-Transducin;",
    "ncbi_link": "Gfp: 
Nrl: 18185"
  },
  {
    "caption": "g, RTqPCR analysis of 100K P8 photoreceptor pellets for Gnat1, Rec, Rho, Crx, Cre and Gfp, relative to β-actin, comparing EVs (N = 8) against the appropriate (Nrl.Gfp+/+ or Nrl.Cre+/-) photoreceptor cell lysate (N = 3). Gnat1, Cre and Gfp mRNA were present in all relevant samples;",
    "ncbi_link": "Gfp: 
β-actin: 11461
Cre: 2777477
Crx: 12951
Gnat1: 14685
Nrl: 18185
Rec: 19674
Rho: 212541"
  },
  {
    "caption": "i, representative flow cytometry analysis of Nrl.Cre+/- & mTmGfloxed co-cultures. Samples were analyzed for expression of myrGFP (recombination) and CD73 (photoreceptor identity) versus CD73-ve fraction (other retinal cells). N > 3 independent cultures for each condition with technical triplicate for each sample; One way ANOVA, non-parametric, Kruskal-Wallis with Dunns' multiple comparisons test",
    "ncbi_link": "Cre: 2777477
Nrl: 18185"
  },
  {
    "caption": "g, Quantification of no. of TdTomato+ve host photoreceptor cells seen following transplantation of live (224 ± 181) versus UV-treated (dead) (3 ± 4) Nrl.Cre+/- P8 photoreceptors (N = 4 eyes per condition). Graph shows mean ± S.D.",
    "ncbi_link": "Cre: 2777477
Nrl: 18185"
  },
  {
    "caption": "i & j, Representative images of depth colour coding (ImageJ) of x,y,z live imaging of Nrl.Gfp+/+ photoreceptor cultures showing (i) neurites (blue arrows) growing along the substrate (asterisks denote secondary branching of long GFP+ neurites), and in (j), a free-floating PhNT (magenta arrow). Scale bar = 10 µm;",
    "ncbi_link": "Gfp: 
Nrl: 18185"
  },
  {
    "caption": "k & l, Quantification of the localization of Nrl.Gfp+/+ processes in the z-axis (depth) (N = 4 independent cultures, n = 1096 cells, nneurites = 440, nnanotubes = 31 where (k) neurites. P values = **** p < 0.0001 (bottom vs top); **p = 0.002 (bottom vs middle); **p = 0.003 (middle vs top) and (l) PhNTs; P-values = **** p < 0.0001 (bottom vs middle & middle vs top) . One way ANOVA, non-parametric, Kruskal-Wallis with Dunns' multiple comparisons test shows means vary significantly.",
    "ncbi_link": "Gfp: 
Nrl: 18185"
  },
  {
    "caption": "d, Lysosomes can be exchanged, rarely, between PhNT-connected cells. Lysosomes were labelled with SiR-Lyso and their movements were analysed by TrackMate software. Images show deconvolution of 3D reconstructions of lysosomes (surface; red) and cGFP (volume; green) from time-lapse live imaging series of Nrl.Gfp+/+ photoreceptor cultures (green); the position of a transferred lysosome is marked as1 (t = 0), 2 (t = 3'), 3 (t = 6'), 4 (t = 9'); N.B. Deconvolution shows a segment-like process extending from cell \"A\" and a PhNT connecting cells \"A\" and \"B\"; Scale bar = 2 µm;",
    "ncbi_link": "Gfp: 
Nrl: 18185"
  },
  {
    "caption": "d, MIP image of wt retina transplanted with P8 Nrl.Gfp+/+ x myrRFP/+ photoreceptors; showing wt host ONL photoreceptor labeled with cGFP (green) but not with myrRFP (red); Scale bar = 50µm; e, quantification and statistical analysis of material transfer events following subretinal transplantation of live (cGFP = 3775 ± 804, myrRFP = 436 ± 145) or UV-treated (cGFP = 1.3 ± 2.5, myrRFP = 4.3 ± 5.7) Nrl.Gfp+/+x myr-Rfp+/+ photoreceptors into wt hosts (N = 8 and N = 4 retinae, respectively); One-way ANOVA, parametric, two tail, Tukey's multiple comparisons; Graph shows mean ± S.D. ",
    "ncbi_link": "Nrl: 18185"
  },
  {
    "caption": "f-h, Assessment of potential for transfer of donor Gfp and Gnat1 mRNA during transplantation using RNAscopeTM. f, Representative MIP images of Gnat1-/- eyes transplanted with Nrl.Gfp+/+ donor cells and processed in situ for Gfp mRNA (red) and Gnat1 mRNA (magenta); blue = nuclei; ROIs indicated in (f) show GFP+ve donor cell mass (CM) and GFP+ve cells within Gnat1-/- host outer nuclear layer (ONL); g & h, quantification of Gfp and Gnat1 mRNA (mean fluorescence intensity per cell), respectively (N = 3 retinae); One-way ANOVA, non-parametric, two tailed analysis showed no significant differences in signal intensity for either Gnat1 or Gfp mRNA between GFP+ve and GFP-ve host photoreceptors;",
    "ncbi_link": "Gfp: 
Gnat1: 14685
Nrl: 18185"
  },
  {
    "caption": "i, Manipulation of actin signalling alters material transfer in vivo: (far left) MIP image showing GFP+ve host photoreceptor (green) expressing Rod α-transducin (red) after transplantation of retinal cells transduced with lenti-CAG-P2A.Gfp (transduction control) into Gnat1-/- recipient; Scale bar = 10 µm; adjacent images show Gnat1-/- eyes transplanted with P2 retinal cells transduced with (left) plenti-CAG-P2A.GFP (green), or (middle) plenti-CAG-RhoA-P2A.GFP (green), or (right) plenti-CAG-ΔΝRac1-P2A.GFP (green); green = GFP, blue = nuclei; Scale bar = 20 µm; j, quantification of the number of GFP+ cells in Gnat1-/- host ONL, (N = 5 retinae per condition); plenti-CAG-P2A.GFP (2328 ± 234), plenti-CAG-RhoA-P2A.GFP (668 ± 481), plenti-CAG-ΔΝRac1-P2A.GFP (547 ± 306); One-way ANOVA, non-parametric, Dunn's multiple comparisons test. Graph shows mean ± SD. ",
    "ncbi_link": "Gfp: 
GFP: 
Gnat1: 14685
Rac1: 19353
RhoA: 11848"
  },
  {
    "caption": "b, Representative tile scan of un-injected Nrl.Cre +/-/TdTomato+/- chimera showing endogenous recombination (white); ROIs, as indicated with dashed or dot boxes; Scale bars = 50 µm;",
    "ncbi_link": "TdTomato: 
Cre: 2777477
Nrl: 18185"
  },
  {
    "caption": "c & d, ROI from un-injected Nrl.Cre +/-/TdTomato+/- chimera showing spontaneous recombination presenting in mosaic stripe patterning; Scale bar = 50 µm in c and 10 µm in d;",
    "ncbi_link": "TdTomato: 
Cre: 2777477
Nrl: 18185"
  },
  {
    "caption": "e & f, Representative images of Nrl.Cre+/-/TdTomato+/- chimera after receiving a subretinal injection of AAV-Nrl.Cre. The injected eyes show widespread recombination, which also shows the anticipated mosaic stripe patterning; Scale bar = 50 µm in (e) and 10 µm in (f);",
    "ncbi_link": "TdTomato: 
Cre: 2777477
Nrl: 18185"
  },
  {
    "caption": "(B) Signal tracks of Med8-MNase and free MNase cleavages at the previously characterized UASs of the CLB2 and RPS5 genes. TSSs are indicated by arrows.",
    "ncbi_link": "CLB2: 856236
RPS5: 853587"
  },
  {
    "caption": "(A) Average plots of Med8 cleavages around the TSSs of SAGA- and TFIID-dependent genes in Kin28AS cells treated with DMSO (-NA-PP1) or 6 μM NA-PP1 (+NA-PP1).",
    "ncbi_link": "Kin28: 851450"
  },
  {
    "caption": "(B) Signal tracks of Med8-MNase cleavages at the upstream regions of several genes previously shown to have increased core promoter association of Mediator by ChIP-qPCR following NA-PP1 treatment of a Kin28AS strain (Wong et al., 2014). All time points for a given treatment were concatenated to generate a combined track. TSSs are indicated by arrows.",
    "ncbi_link": "Kin28: 851450"
  },
  {
    "caption": "(A) Average plot of Med8 cleavages around 193 Gcn4ChIP-chip peak midpoints (MacIsaac et al., 2006) in WT and med15Δ.",
    "ncbi_link": "Gcn4: 856709"
  },
  {
    "caption": "(B) Average plots of Med8 cleavages around the TSSs of genes upregulated and downregulated ≥2 fold in SM (Saint et al., 2014) in WT and med15Δ. Control cleavages were subtracted from SM cleavages at each base position.",
    "ncbi_link": "med15: 854106"
  },
  {
    "caption": "(C) qRT-PCR analysis of SAGA- and TFIID-dependent genes in WT and med15Δ. Bars represent mean + SEM for two biological replicates performed in triplicate. *, p < 0.05; †, p < 0.01; ‡, p < 0.005 by unpaired Student's t-test.",
    "ncbi_link": "med15: 854106"
  },
  {
    "caption": "G, H. U1 Grx1-roGFP2 cells were supplemented with BSO (G) or GSH (H) for 16 h to deplete or replenish GSH, respectively. Following this, cells were treated with Vs for 15 min, exposed to H2O2, and the ratiometric response was measured.",
    "ncbi_link": "roGFP2: 
Grx1: 2745"
  },
  {
    "caption": "E. U1-Grx1-roGFP2 cells were serum starved for 30 min in the presence or absence of Vs and sodium selenite (0.5 nM), and the biosensor response was measured. Data were compared to serum starved control cells (C).",
    "ncbi_link": "roGFP2: 
Grx1: 2745"
  },
  {
    "caption": "F. U1 cells were either serum-starved or supplemented with Se (0.5 nM) or Vs (0.62 ng/μL) and HIV reactivation was measured at 6 h post starvation by gag RT-PCR.",
    "ncbi_link": "gag: 155030"
  },
  {
    "caption": "Total RNA isolated from untreated (UT), PMA-treated, Vs-treated and Vs+PMA treated U1 was examined by NanoString technology to assess the expression of genes responsive to oxidative stress and HIV. (C Heat map showing functional categories of DEGs under PMA/UT, Vs/UT and PMA+Vs/UT comparisons. mRNA counts were normalised using the internal control β2 microglobulin (B2M), and fold change (FC) was calculated using the nSolver 4.0 software. Genes showing an absolute FC >1.5, and P <0.05 were considered as significantly altered.",
    "ncbi_link": "B2M: 567
β2 microglobulin: 567"
  },
  {
    "caption": "Total RNA isolated from untreated (UT), PMA-treated, Vs-treated and Vs+PMA treated U1 was examined by NanoString technology to assess the expression of genes responsive to oxidative stress and HIV. D) Heat map showing functional categories of DEGs under PMA/UT, Vs/UT and PMA+Vs/UT comparisons. mRNA counts were normalised using the internal control β2 microglobulin (B2M), and fold change (FC) was calculated using the nSolver 4.0 software. Genes showing an absolute FC >1.5, and P <0.05 were considered as significantly altered.",
    "ncbi_link": "B2M: 567
β2 microglobulin: 567"
  },
  {
    "caption": "B-D. A similar assay was performed using Jurkat (CD4+ T cell line) and viral replication was assessed by (B) gag RT PCR, (C) p24 ELISA in the culture supernatant, and (D) immunoblotting for p24 (viral capsid protein) in the whole cell lysate.",
    "ncbi_link": "gag: 155030"
  },
  {
    "caption": "(B) Flp-In T-REx 293 cells with induced MIA40FLAG expression were solubilized, and the affinity purification of MIA40FLAG was performed. Fractions were analyzed by SDS-PAGE and Western blot. Load: 2.5 %. Eluate: 100 %. Unbound: 2.5 %.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "(C) Flp-In T-REx 293 cells with induced MIA40FLAG expression were solubilized, and the affinity purification of MIA40FLAG was performed. Eluate fractions were solubilized under reducing (DTT) or non-reducing (IAA) conditions and analyzed by SDS-PAGE and Western blot. DTT, dithiothreitol; IAA, iodoacetamide. Eluate: 100 %.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "(D) Cellular protein extracts from Flp-In T-REx 293 cells with induced expression of wildtype or mutant MIA40FLAG were subjected to affinity purification. Load and eluate fractions were analyzed by reducing SDS-PAGE and Western blot. Load: 2.5 %. Eluate: 100 %.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "(D) N-SIM super-resolution micrographs of one Z-stack (0.15 μm) orthogonal section (XYZ) of HeLa cells or HeLa cells that stably expressed COA7-HA transfected with different markers TOMM20-DsRed (OM), COX8A-DsRed (IM), and matrix targeted photoactivatable GFP (Matrix target) labeled with anti-HA, anti-COA7 and Smac/Diablo (IMS) antibodies. The picture represents the majority population of cells from three independent experiments. Scale bar = 2 μm, scale bar in the magnified insert = 0.5 μm. The panel shows Pearson's coefficient in a co-localized volume of different subcompartment combinations with anti-HA or anti-COA7. The data are expressed as a mean ± SD (n=5). ***p<0.001 [IMSxEnd vs. IMxEnd p=0.0001; IMSxEnd vs. MxEnd p=0.0002], ****p<0.0001 [OMxHA vs. IMSxHA p<0.0001; IMSxHA vs. IMxHA p<0.0001] (one-way ANOVA). M, matrix; End, endogenous COA7; HA, COA7-HA.",
    "ncbi_link": "HA: 
COA7: 65260
COX8A: 1351
TOMM20: 9804"
  },
  {
    "caption": "(A) Mitochondria were isolated from cells that were transfected with a plasmid that encoded COA7HIS or an empty vector. Mitochondria were solubilized and analyzed by reducing SDS-PAGE and Western blot. Mitos, mitochondria.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(B) Radiolabeled [35S]TIMM8A and [35S]COX19 precursors were imported into mitochondria that were isolated from cells that were transfected with a plasmid that encoded COA7HIS or an empty vector. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological replicates were analyzed, quantified, and normalized to control mitochondria at 30 min. The data are expressed as a mean ± SEM (n=3). IAA, iodoacetamide.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(C) Mitochondria were isolated from cells that were transfected with a plasmid that encoded COA7HIS or an empty vector under reducing (DTT) and non-reducing (IAA) conditions and analyzed for levels of MIA40 by Western blot.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(D) Proteins from HEK293 cells transfected with empty plasmid or RESA1HIS were modified with PEG-PCMal. Control cells were pretreated with the thiol oxidizing agent diamide (DAM) or the reductant DTT. The samples were analyzed by SDS-PAGE and Western blot.",
    "ncbi_link": "HIS: 
RESA1: 65260"
  },
  {
    "caption": "(E) Flp-In T-REx 293 cells induced to express MIA40FLAG were transfected with a plasmid that encoded COA7HIS or an empty vector. The affinity purification of MIA40FLAG was performed, and eluate fractions were analyzed by SDS-PAGE and Western blot.",
    "ncbi_link": "FLAG: 
HIS: 
COA7: 65260"
  },
  {
    "caption": "Radiolabeled [35S]COA7 (A) precursors were imported into mitochondria that were isolated from Flp-In T-REx 293 cells induced to express MIA40FLAG. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological replicates were analyzed, quantified, and normalized to control mitochondria at 45 min. The data are expressed as a mean ± SEM (n=3). IAA, iodoacetamide.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "Radiolabeled [ 35S]TIMM8A (B) precursors were imported into mitochondria that were isolated from Flp-In T-REx 293 cells induced to express MIA40FLAG. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological replicates were analyzed, quantified, and normalized to control mitochondria at 45 min. The data are expressed as a mean ± SEM (n=3). IAA, iodoacetamide.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "(C) Mitochondria were isolated from Flp-In T-REx 293 cells induced to express MIA40FLAG and control cells. The samples were analyzed by SDS-PAGE and Western blot. Mitos, mitochondria.",
    "ncbi_link": "FLAG: "
  },
  {
    "caption": "Radiolabeled [35S] COA7 (D) precursors were imported into mitochondria that were isolated from Flp-In T-REx 293 cells induced to express ALRFLAG and control cells. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological experiments were analyzed, quantified, and normalized to control mitochondria at 45 min. The data are expressed as a mean ± SEM (n=3).",
    "ncbi_link": "FLAG: 
ALR: 2671"
  },
  {
    "caption": "Radiolabeled [35S] TIMM8A (E) precursors were imported into mitochondria that were isolated from Flp-In T-REx 293 cells induced to express ALRFLAG and control cells. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological experiments were analyzed, quantified, and normalized to control mitochondria at 45 min. The data are expressed as a mean ± SEM (n=3).",
    "ncbi_link": "FLAG: 
ALR: 2671"
  },
  {
    "caption": "(F) Mitochondria were isolated from Flp-In T-REx 293 cells induced to express ALRFLAG and control cells. The samples were analyzed by SDS-PAGE and Western blot.",
    "ncbi_link": "FLAG: 
ALR: 2671"
  },
  {
    "caption": "(B) Cellular protein extracts were isolated from HeLa cells transfected with oligonucleotides that targeted different regions of ALR mRNA or with control oligonucleotides. The samples were analyzed by reducing SDS-PAGE and Western blot.",
    "ncbi_link": "ALR: 2671"
  },
  {
    "caption": "(B) Cellular protein extracts were isolated from HEK293 cells that were transfected with a plasmid that encoded wildtype or mutant COA7. The samples were analyzed by reducing SDS-PAGE and Western blot.",
    "ncbi_link": "COA7: 65260"
  },
  {
    "caption": "(C) Cellular fractions were prepared from HEK293 cells that were transfected with a plasmid that encoded wildtype or mutant COA7. The fractions were analyzed by reducing SDS-PAGE and Western blot. T, total; C, cytosol; M, mitochondria.",
    "ncbi_link": "COA7: 65260"
  },
  {
    "caption": "(D) HEK293 cells that transiently expressed wildtype or mutant COA7HIS were solubilized, and the affinity purification of COA7HIS was performed. The samples were analyzed by reducing and non-reducing SDS-PAGE and Western blot. Load: 3 %. Eluate: 100 %.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(E) Equal amounts of wildtype and mutant radiolabeled [35S]COA7 precursors were imported into mitochondria isolated from HEK293 cells. The samples were analyzed by reducing SDS-PAGE and autoradiography. The results of three biological replicates were analyzed, quantified, and normalized to wildtype COA7 at 45 min. The data are expressed as a mean ± SEM (n=3). IAA, iodoacetamide.",
    "ncbi_link": "COA7: 65260"
  },
  {
    "caption": "(B) HEK293 cells that transiently expressed wildtype or mutant COA7HIS were treated with CHX for the indicated times, and protein extracts were isolated. The samples were analyzed by reducing SDS-PAGE and Western blot.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(D) HEK293 cells that transiently expressed wildtype or mutant COA7HIS were treated with CHX and/or MG132 for the indicated times, and protein extracts were isolated. The samples were analyzed by reducing SDS-PAGE and Western blot. CHX, cycloheximide.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(F) Cellular fractions were prepared from HEK293 cells that transiently expressed mutant COA7HIS and were treated with MG132. The samples were analyzed by reducing SDS-PAGE and Western blot.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "(C) Immortalized patient-derived skin fibroblasts transiently expressing wildtype or mutant COA7 (COA7-Y137C and COA7-Ex2∆) for 48 h were treated with bortezomib (20 nM) during the last 12 h. The fibroblasts were harvested, and complex IV activity was measured in digitonized cellular extracts. The results of three biological replicates were quantified and normalized to empty vector-bortezomib treated samples and the data are expressed as a mean ± SEM (n=3, *p=0.01 [Empty vector vs COA7- Wt], *p=0.005 [Empty vector vs COA7 - Y137C]).",
    "ncbi_link": "COA7: 65260"
  },
  {
    "caption": "(E) Immortalized patient-derived skin fibroblasts transfected with plasmid encoding wtCOA7HIS and COA7-Y137CHIS were solubilized in DDM buffer and analyzed by 4-13 % gel BN-PAGE and Western blot.",
    "ncbi_link": "HIS: 
COA7: 65260"
  },
  {
    "caption": "LC-MS-MS analysis of in-gel-digested HEK293 cells transfected with hNICD-GFP, and subjected to immunoprecipitation using GFP antibody, identified multiple phosphorylation sites in NICD, highlighted in green.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Phosphorylation of serine 2513, but not serine 2516, appears to be essential for the NICD-FBXW7 interaction. hNICD-GFP phospho-mutant peptides encoding non-phosphorylatable residues at S2513 and/or 2516 (serine to alanine) were expressed in HEK293 cells. The exogenously expressed protein was subsequently immunoprecipitated with anti-GFP antibody and precipitated material was analysed by western blot using FBXW7 antibody. Wild-type hNICD-GFP and GFP only vectors were included as positive and negative controls, respectively. Western blot using GFP antibody served as immunoprecipitation efficiency control. β-Actin has been used as loading control for the input lanes.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "HEK293 cells were cultured for 48h after transfection with plasmids encoding scrambled siRNA (-) or siRNA specific for CDK2 (+) followed by western blot for NICD, CDK2, CDK1, CDK4 and CDK8. β-Actin served as loading control.   Quantification of the density of western blot bands in (A) performed by ImageJ software. Data are expressed as fold changes compared to control (scrambled siRNA transfected) cell lysate. All data represent the mean ± SEM from three independent experiments. Student's t-test analysis was performed, with **p≤0.01.   ",
    "ncbi_link": "CDK2: 1017"
  },
  {
    "caption": "HEK293 cells were cultured for 48h after transfection with plasmids encoding scrambled siRNA (-) or siRNA specific for CDK1 (+) followed by western blot for NICD, CDK1, CDK2, CDK4 and CDK8. β-Actin has been used as loading control.   Quantification of the density of western blot bands in (C) performed by ImageJ software. Data are expressed as fold changes compared to control (scrambled siRNA transfected) cell lysate. All data represent the mean ± SEM from three independent experiments. Student's t-test analysis was performed, with *p≤0.05.   ",
    "ncbi_link": "CDK1: 983"
  },
  {
    "caption": "Graph of flow cytometry data shows the percentage of cells in given cell‐cycle phases 48h after transfection with plasmids encoding scrambled siRNA or siRNA specific for CDK2. Graph represents the mean of three independent experiments. All data represent the mean ± SEM from three independent experiments. Student's t-test analysis was performed, with **p≤0.01 (ns=not significant).",
    "ncbi_link": "CDK2: 1017"
  },
  {
    "caption": "Graph of flow cytometry data shows the percentage of cells in given cell‐cycle phases 48h after transfection with plasmids encoding scrambled siRNA or siRNA specific for CDK1. Graph represents the mean of three independent experiments. All data represent the mean ± SEM from three independent experiments. Student's t-test analysis was performed, with *p≤0.05 and **p≤0.01.",
    "ncbi_link": "CDK1: 983"
  },
  {
    "caption": "Bissected E10.5 mouse PSM explants were cultured in the absence (-) or presence (+) of 1µM of Purvalanol B for 4 hours and then analysed by in situ hybridization for mLfng mRNA expression. Purvalanol B treated explant has one less somite than the control explant and the treated explant is in the same late phase 1 of the oscillation cycle of dynamic mLfng mRNA expression indicating it is a whole cycle delayed compared to the "-" explant. n=18. Scale bar is 100 µm.",
    "ncbi_link": "Lfng: 16848"
  },
  {
    "caption": "Bissected E10.5 mouse PSM explants were cultured in the absence (-) or presence (+) of 10 µM of RO-3306 for 4 hours and then analysed by in situ hybridization for mLfng mRNA expression. RO-3306 treated explant is two phases behind in the oscillation cycle of dynamic mLfng mRNA expression indicating there is a delay in the oscillation compared to the "-" explant. n=10. Scale bar is 100 µm.",
    "ncbi_link": "Lfng: 16848"
  },
  {
    "caption": "(A) HEK cells transfected with STIM1-CFP, Orai1-mCherry, and with (red) or without (black) untagged ANO8 were used to measure CRAC current with pipette solution (cytoplasmic buffer) containing 3 mM EGTA. The columns show the averaged effect of ANO8 on current density and on the slop of slow Ca2+-dependent inactivation (SCDI). The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
mCherry: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(B) Fura2-loaded HEK cells transfected with YFP (control, black) or ANO8-YFP (red) were used to measure store-mediated Ca2+ influx. Stores were depleted by treatment with the SERCA inhibitor CPA and Ca2+ influx was measured by Ca2+ add-back. The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "YFP: 
ANO8: 57719"
  },
  {
    "caption": "(C) FRET efficiency was measured with HEK cells transfected with STIM1-CFP, ANO8-YFP, and with (red) and without (black) Orai1-HA before and after store depletion. Here and all other FRET measurements, representative images of the FRET signal under each condition are shown next to the traces. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
HA: 
YFP: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(E) FRET efficiency was measured with HEK cells transfected with STIM1-CFP, STIM1-YFP (blue), and co-transfected with untagged ANO8 (green) or treated with siANO8 (red) before and after store depletion. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
YFP: 
ANO8: 57719
STIM1: 6786"
  },
  {
    "caption": "(F) Resting (R) or store-depleted cells (S) HEK cells transfected with STIM1-YFP and myc-STIM1 and with or without ANO8 or treated with siANO8, were used to immunoprecipitate (IP) STIM1-YFP and blot (B) for mys-STIM1. The inputs (In) are with anti-myc, anti-YFP or anti-ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "myc: 
YFP: 
ANO8: 57719
STIM1: 6786"
  },
  {
    "caption": "(G) Confocal and bright field images of basal (upper) and store depleted cells (lower) of HEK cells transfected with ANO8-YFP alone. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed. The experiments represent at least 4 separate experiments with similar results.",
    "ncbi_link": "YFP: 
ANO8: 57719"
  },
  {
    "caption": "(H) TIRF images (upper) and TIRF-Z scan (lower) of the same resting and store depleted cells HEK cells transfected with ANO8-YFP alone. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed. The experiments represent at least 4 separate experiments with similar results.",
    "ncbi_link": "YFP: 
ANO8: 57719"
  },
  {
    "caption": "(I): Confocal images of resting cells transfected with ANO8-YFP, STIM1-CFP and Orai1-mCherry. (J) Confocal images of store depleted cells transfected with ANO8-YFP, STIM1-CFP and Orai1-mCherry. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed. The experiments represent at least 4 separate experiments with similar results.",
    "ncbi_link": "CFP: 
mCherry: 
YFP: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(K) TIRF-Z scan of resting (upper) and store depleted (lower) cells transfected with ANO8-YFP and STIM1-mCherry demonstrating the relationship between STIM1 and ANO8 puncta at the TIRF field. Cell surface is on top. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed. The experiments represent at least 4 separate experiments with similar results.",
    "ncbi_link": "mCherry: 
YFP: 
ANO8: 57719
STIM1: 6786"
  },
  {
    "caption": "(A) FRET ratio was measured with HEK cells transfected with STIM1-CFP, Orai1-YFP (black) and co-transfected with untagged ANO8 (red) before and after store depletion with 25 µM CPA in Ca2+-free solution. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
YFP: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "TIRF microscopy was used to quantify puncta formation at the TIRF field in cells transfected with STIM1-CFP, ANO8-YFP and Orai1-mCherry before and after store depletion. (A) Example images. (B) Time course of STIM1 puncta formation in cells transfected with STIM1 and Orai1 alone (black) or together with ANO8 (red). Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
mCherry: 
YFP: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(C-E) Effect of ANO8 on the rate of STIM1-STIM1 clustering (C), number of STIM1 puncta (D) and number of Orai1 puncta (E). The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(G) HEK cells treated with scrambled (siScr) or siANO8 (siA8) were used to IP the native Orai1 (O1) or STIM1 (S1) and blotted (B) for the native STIM1, Orai1 or ANO8, as indicated. The columns show the mean±s.e.m of 4 independent experiments. The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "A8: 57719
ANO8: 57719"
  },
  {
    "caption": "(I) Effect of ANO8-YFP on myc-STIM1 and Orai1-HA at the ER/PM junction. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "YFP: 
ANO8: 57719"
  },
  {
    "caption": "(M) Example EM images recorded from HEK cells transfected with empty vector (left) or ANO8 (right). Red arrows mark ER/PM junctions. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(N, O) The size (N) and density (O) of ER/PM junctions in vector-transfected (control) and ANO8-transfected cells. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(A, B) Knockdown of ANO8 (siA8) reduced CRAC current in cells transfected with Orai1 (O1) and STIM1 (S1) and buffered with 3 mM EGTA. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed and difference were analyzed by unpaired t test.",
    "ncbi_link": "A8: 57719
ANO8: 57719
O1: 84876
Orai1: 84876
S1: 6786
STIM1: 6786"
  },
  {
    "caption": "(C) Knockdown of ANO8 reduces the native store-dependent Ca2+ influx measured in store depleted cells by Ca2+ add-back. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(D,E) Knockdown of ANO8 reduced the number of store-dependent STIM1 puncta at the TIRF plane in cells expressing STIM1 and Orai1. Panel (D) shows representative images and (E) is the summary of 7 experiments. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(F, G) Current was measured with pipette solution contacting the fast and strong Ca2+ buffer 10 mM BAPTA in HEK cells transfected with STIM1, Orai1, and with (red) or without ANO8 (black). Panel (G) shows the increase in current density at peak current. Note the prominent current inactivation in the presence of ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(H) Knockdown of SARAF (red) in wild-type cells had no effect on current inactivation in the presence of 10 mM BAPTA. (I) Knockdown of SARAF did not prevent the ANO8-dependent current inactivation in the presence of 10 mM BAPTA. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed and difference were analyzed by unpaired t test. ",
    "ncbi_link": "ANO8: 57719
SARAF: 51669"
  },
  {
    "caption": "(A, B) Depletion of plasma membrane PI(4,5)P2 with the FRB/FKBP system prevented the ANO8-mediated increase in STIM1-Orai1 current measured in pipette solutions containing 3 mM EGTA (A) or 10 mM BAPTA (B). Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(C) HEK cells transfected with ANO8-YFP, STIM1-CFP Orai1-HA and FRB and mCherry-FKBP PI(4,5)P2 depleting constructs were treated with 0.2 µM rapamycin (rapa) for 5 min and then with 25 µM CPA for 10 min before fixation and imaging by confocal microscopy. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "CFP: 
FKBP: 
FRB: 
HA: 
mCherry: 
YFP: 
ANO8: 57719
Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(D) Mutating ANO8 R948, R950, R951 in RPRRP, a region that is predicted to include an ANO8 PI(4,5)P2 binding site, prevented increased STIM1-Orai1 current and inactivation. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(E) Mutating ANO8 R949,950,951 to Q reduced translocation of ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(A) Plot of the slope of inactivation as a function of current density in the presence (red) and absence of ANO8 (black). Increasing current density was obtained by varying external Ca2+ between 2-50 mM. The results are mean±s.e.m and difference were analyzed by unpaired t test. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(D, E) Experimental protocol and conditions except that cells were also transfected with ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(F, G) HEK cells expressing STIM1, Orai1, and ANO8 were used to measure current in pipette solution containing 10 mM BAPTA and with (red) or without (black) 100 µM IP3 or 10 mM of the ER Ca2+ chelator TPEN (green). The current density (F) and the normalized current (G) are shown, illustrating the delay in current inactivation by IP3 and TPEN. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed.",
    "ncbi_link": "Orai1: 84876
STIM1: 6786"
  },
  {
    "caption": "(A, B): ER Ca2+ content was measured with ER-GECO1 in the periphery (A) and the center (B) or cells transfected with M3 receptors and with (red, green) or without (black, blue) ANO8. Receptor mediated store depletion was initiated by stimulating the cells with 0.5 mM carbachol in Ca2+-free solution. Cell stimulation was terminated with 10 µM atropine and ER Ca2+ uptake was initiated by perfusing the cells with a solution containing 5 mM Ca2+. The fluorescence was measured as F/F0 and normalized to the initial fluorescence in the presence of ANO8. Panel (C) shows traces of ER Ca2+ uptake at expanded time scale in the periods marked by rectangular in (A and B) and the averaged slopes of ER Ca2+ influx and (D) shows the averaged slope of Ca2+ release at the cell periphery (Peri) and cell center (Center). In (C) the traces were aligned along the Y axis to better show the difference in uptake rate. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(E) Enhancement by ANO8 of the Co-IP of expressed STIM1 with PMCA4a and SERCA2 and of Orai1 with SERCA2 in resting and store depleted cells. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(F) Effect of ANO8 expression on the Co-IP of the native SERCA2 and STIM1 in resting and store depleted cells. The columns are the mean±s.e.m of 3 experiments. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(G) FRET ratio between STIM1 and SERCA2 in response to store depletion and its enhancement by ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(J) Effect of ANO8 on the Co-IP of the native STIM1 and IP3Rs. The columns are the mean±s.e.m of 3 experiments. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(K) FRET ratio between expressed STIM1 and IP3R3 in response to store depletion and its enhancement by ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(L) FRET ratio between expressed STIM1 and PMCA4 in response to store depletion and its enhancement by ANO8. Data information: The first number in parenthesis indicates the number of similar experiments performed and the second number is the number of cells analyzed. All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(A-D) HeLa cells transfected with GFP (black) or ANO8 (red) were stimulated with 0.5 and then 1 µM ATP to activate the native P2Y2 receptors. The oscillations were analyzed in terms of the % of responding cells (B), oscillation frequency (C), and the amplitude of the Ca2+ signal (D). Data information: All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "GFP: 
ANO8: 57719"
  },
  {
    "caption": "(E-H): HeLa cells were treated with scrambled siRNA (black) or siANO8 (red) and were stimulated with 1 and then 5 µM ATP. The oscillations were analyzed in terms of the % of responding cells (F), oscillations frequency (G), and the amplitude of the Ca2+ signal (H). Data information: All results are given as mean±s.e.m of the indicated number of experiments or cells analyzed, and difference were analyzed by unpaired t test.",
    "ncbi_link": "ANO8: 57719"
  },
  {
    "caption": "(A) RT-qPCR analysis of NimB1,  NimB2, NimB3, NimB4 and NimB5  transcripts, normalized to RpL32, from carcass, macrophages, fat body  and  gut  of wild type (w1118) L3 wandering larvae. Data are represented as mean ± SD from three independent experiments.",
    "ncbi_link": "NimB1: 34813
NimB2: 260645
NimB3: 3885611
NimB4: 34814
NimB5: 34815
RpL32: 43573"
  },
  {
    "caption": "(A) Representative  confocal imaging of wild type (w1118), NimB4 sk2 and apoptosis-null NimB4 sk2; Df(3L) H99 embryonic macrophages  at stage 16 of development; ventral and lateral view; Tissues were co-stained with Dcp-1 (red, corresponding to apoptotic corpses) and anti-SIMU  (green, corresponding to macrophages) antibodies. The arrows show the presence of apoptotic cells  inside embryonic macrophages. Scale bars = 20 μm",
    "ncbi_link": "NimB4: 34814"
  },
  {
    "caption": "(C) Representative projections from confocal  stacks of entire third instar wild type (w1118) and NimB4 sk2 larval brains stained  with anti-Draper  (green) and anti-Dcp1 (red). The arrows show the presence of  apoptotic cells  in the central area of  NimB4 sk2 larval brain. Scale bars = 100 μm",
    "ncbi_link": "NimB4: 34814"
  },
  {
    "caption": "(A) Representative  confocal imaging of wild type (w1118), NimB4 sk2 and draper macrophages incubated with fluorescently-labeled apoptotic cells (red, CellTraceTM Red) on ice for 1h and stained  with AlexaFluorTM 488 phalloidin  (green). Scale bar: 10 μm. (B) Quantification of the  number  of  apoptotic cells (red)  binding to the  macrophages  (green). Values from three independent experiments are represented as mean ± SD (*** P<0.001 by ANOVA test followed by post hoc Dunnett's multiple comparison tests. ns: not significant). ",
    "ncbi_link": "draper: 38218
NimB4: 34814"
  },
  {
    "caption": "(D) Ex vivo phagocytosis assay  using Alexa555 fluorescent apoptotic bodies. Wild type, NimB4sk2, NimB4 genomic rescue (NimB4sk2, [NimB4]), draper and NimC11,  eater1 macrophages from L3 wandering were incubated with Alexa555 fluorescent apoptotic bodies for 30, 60 or 120 min at room temperature. Phagocytosis  was quantified by flow cytometry. Data are represented as mean ± SD from three independent experiments (* P<0.05,** P<0.01, **** P<0.0001 by ANOVA test followed by post hoc Dunnett's multiple comparison tests ns: not significant). (E) Ex vivo phagocytosis assay  using  AlexFluor488 S.aureus Bioparticles. Wild type, NimB4sk2 and NimC11, eater1 macrophages from L3 wandering were incubated with  bioparticles for 30, 60 or 120 min at room temperature. Phagocytosis  was quantified by  flow cytometry. Data are represented as mean ± SD from three independent experiments (**** P<0.0001 by ANOVA test followed by post hoc Dunnett's multiple comparison tests. ns: not significant). ",
    "ncbi_link": "draper: 38218
eater: 43262
NimB4: 34814
NimC1: 34816"
  },
  {
    "caption": "(A) Representative fluorescence microscopy images of wild type (w1118),  NimB4sk2, draper, eater1 and croquemort△ third instar larvae macrophages stained with LysoTracker Red (live imaging). Overlay of fluorescence and differential interference contrast microscopy  (DIC). Scale bar = 10 μm. (B) Mean fluorescence intensity after  staining  with LysoTracker Red (live confocal imaging). Values from at least three independent experiments are represented as mean ± SD ( ** P<0.01, **** P<0.0001 by ANOVA test followed by post hoc Dunnett's multiple comparison tests). ",
    "ncbi_link": "croquemort: 33219
draper: 38218
eater: 43262
NimB4: 34814"
  },
  {
    "caption": "(C) Representative transmission electron micrographs of macrophages from wild type (top, w1118) and NimB4sk2 (bottom) L3 wandering larvae. Scale bar: 2 μm (D) Quantification of the number of vesicles  per  macrophages in the electron micrographs. Values from at least three independent experiments are represented as mean ± SD (**** P<0.0001 by Mann-Whitney test). ",
    "ncbi_link": "NimB4: 34814"
  },
  {
    "caption": "(E) Representative confocal imaging of Rab7EYFP immunostaining in wild type (w1118) and NimB4 sk2 macrophages. Tissues were stained with anti-GFP (red, Rab7), counterstained with  phalloidin (gray) and  DAPI  (blue). The arrows indicate the enlarged vesicles  are decorated with Rab7EYFP in the NimB4sk2 macrophages. Scale bar = 10 μm.",
    "ncbi_link": "NimB4: 34814"
  },
  {
    "caption": "(A) Representative confocal imaging of localization  of  Lamp1-mcherry and LysoTracker Green in wild type (w1118), NimB4 sk2 and draper△5 macrophages (live imaging). The arrows indicate the colocalization (w1118) or the clustering (NimB4sk2 and draper△5) of  Lamp1-mcherry and LysoTracker Green signals. Scale bar: 10 μm. (B) Quantification of the  colocalization of Lamp1-mcherry with LysoTracker Green, as measured by Pearson's correlation coefficient between the two signals. Values from at least five independent experiments are represented as mean ± SD (* P<0.05 by ANOVA test followed by post hoc Dunnett's multiple comparison tests). ",
    "ncbi_link": "draper: 38218
NimB4: 34814"
  },
  {
    "caption": "(C) Ex vivo phagocytosis assay using apoptotic cells labelled with  pHrodo™ Red. Wild type (w1118), NimB4sk2 and draper△5 macrophages from L3 wandering larvae were incubated with pHrodo™ Red apoptotic cells for 60 min at room temperature.  Phagocytosis was quantified by  flow cytometry. Data are represented as mean ± SD from three independent experiments (* P<0.05 by ANOVA test followed by post hoc Dunnett's multiple comparison tests. ns: not significant). (D) Ex vivo phagocytosis assay using pHrodoTM Red S.aureus BioparticlesTM conjugates. Wild type, NimB4sk2 and NimC11, eater1 Hml∆-Gal4>UAS-GFP macrophages from L3 wandering  larvae were incubated with  pHrodoTM Red S. aureus BioparticlesTM for 30, 60 or 120 min at room temperature. Phagocytosis was quantified by  flow cytometry. Data are represented as mean ± SD from three independent experiments (* P<0.05by ANOVA test followed by post hoc Dunnett's multiple comparison tests. ns: not significant). ",
    "ncbi_link": "GFP: 
draper: 38218
eater: 43262
Gal4: 855828
Hml: 39529
NimB4: 34814
NimC1: 34816"
  },
  {
    "caption": "(A-B) Representative fluorescence microscopy images of wild type (A) or NimB4sk2 (B) macrophages expressing Rab5  (middle panel) or  Rab7 (right panel) driven by Hml∆-Gal4 and stained with the  LysoTracker Red  (live imaging). Overlay of fluorescence and DIC. Scale bar = 10 μm. (C) Quantification of the mean fluorescence intensity of  LysoTracker in macrophages from  larvae (confocal live imaging). Values from at least three independent experiments are represented as mean ± SD (** P<0.01, **** P<0.0001 by ANOVA test followed by post hoc Dunnett's multiple comparison tests. ns: not significant). ",
    "ncbi_link": "Gal4: 855828
Hml: 39529
NimB4: 34814"
  },
  {
    "caption": "Representative microscopic views of Ndrg4+/+ and Ndrg4-/- murine intestinal sections (n=4, 12 months of age) reveal an even distribution of alkaline phosphatase along the enterocyte brush border, and a similar number and distribution of Paneth cells (Lysozyme) in the small intestine; and neuroendocrine (Chromogranin A), Goblet (PAS+), and proliferating (Ki67) cells in the colon. Scale bars, 50 µm.",
    "ncbi_link": "Ndrg4: 234593"
  },
  {
    "caption": "Representative microscopic views of the myenteric plexus of Ndrg4+/+ and Ndrg4-/- murine colonic sections labeled with either TuJ1 and S100 (B, n=3) or HuC/D (C, n=6) did not reveal structural or organizational differences in the ganglionic network of Ndrg4+/+ and Ndrg4-/- mice. Scale bars, 100 µm. Quantification of the enteric neuronal cell number (HuC/D) shows a similar number of enteric neurons in the proximal and distal colon of Ndrg4+/+ and Ndrg4-/- mice (n=6).",
    "ncbi_link": "HuC/D: 16016
Ndrg4: 234593
S100: 100344971
TuJ1: 22152"
  },
  {
    "caption": "In contrast, Ndrg4fl/fl and Ndrg4fl/fl-VillinCre mice have a similar bodyweight (I) and develop an equal number of adenomas (J) with an equivalent diameter (K,L). N=13 vs. 12 in I, n=13 vs. 11 in J and n=10 vs. 8 in K.",
    "ncbi_link": "Cre: 2777477
Ndrg4: 234593
Villin: 22349"
  },
  {
    "caption": "Compared to Ndrg4+/+ ENS-derived medium, addition of medium derived from Ndrg4-/- ENS cultures enhances the relative growth of intestinal epithelial organoids (E, IEOs) and accelerates the formation of new crypt buds per IEO in the course of five days (F).",
    "ncbi_link": "Ndrg4: 234593"
  },
  {
    "caption": "Box plot showing the quantitative protein expression results of nanoLC-MS/MS analysis reveals the significantly higher presence of Nid1 and Fbln2 in the Ndrg4-/- compared to the Ndrg4+/+ ENS cell secretome (n=4; NSAF, normalized spectral abundance factor). Data are analyzed with R version 3.5.2 and the ibb R package. Each dot within the box plot represents the NSAF of an individual sample; the inside band reflects the median, and the bottom and top of the box the first and third quartile, respectively. The whiskers reflect the minimum and maximal values within 1.5× the interquartile range. NSAF values were compared using the Mann-Whitney U test.",
    "ncbi_link": "Ndrg4: 234593"
  },
  {
    "caption": "(E) The expression of GSC maintenance genes (aret, Mei-P26, egg, Myc and Hrb98DE) and differentiation genes (bam, bgcn, out, twin and Set1) along the primary branch (dotted circle line) in pseudotime.",
    "ncbi_link": "bam: 43038
bgcn: 47873
aret: 34648
egg: 37962
Hrb98DE: 43385
Mei-P26: 45775
Myc: 31310
out: 32926
Set1: 3354971
twin: 42880"
  },
  {
    "caption": "(C-C') Immunofluorescence staining with anti-TfIIA-S on wild type and nos-Gal4>UAS-TfIIA-S-RNAi (negative control). The scale bar is 10 μm.",
    "ncbi_link": "Gal4: 855828
nos: 42297
TfIIA-S: 42822"
  },
  {
    "caption": "(E-E') Immunofluorescence staining with anti-eggpl on wild type and nos-Gal4>UAS-eggpl-RNAi (negative control) ovary. The scale bar is 10 μm.",
    "ncbi_link": "eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(F) The overexpression of GFP (green) and eggpl in Sf9 cell line in vitro. The anti-eggpl (red) was used to detect the eggpl protein, and Hoechst (blue) was used to label the nucleus. The scale bar is 10 μm.",
    "ncbi_link": "eggpl: 318223"
  },
  {
    "caption": "(A-A') The mRNA in situ hybridization of eggpl (green) on wild type and nos-Gal4>UAS-eggpl-RNAi (negative control) line. The scale bar is 10 μm. (B-C) Immunofluorescence staining with anti-α-Spectrin (red) and anti-Vasa (red) on eggpl-in situ (green) labeled tissues respectively. The scale bar is 10 μm. The dashed line indicates the eggpl-in situ (green) signals.",
    "ncbi_link": "eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(F and H) The mRNA in situ hybridization of eggpl (green) on nos-Gal4>UAS-eggpl-RNAi (negative control) (F) and nos-Gal4>UAS-eggpl-GFP lines (H). The scale bar is 10 μm. (G) The anti-GFP, anti-α-Spectrin (red) and anti-Bam (blue) were used to stain on eggpl::GFP knock-in line. The scale bar is 10 μm. (I) Double staining with eggpl in situ and anti-GFP on eggpl knock-in lines. The scale bar is 10 μm. The dashed line indicates the eggpl-in situ (green) signals.",
    "ncbi_link": "GFP: 
eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(K) The phenotypes of wild type, nos-Gal4>UAS-eggpl-RNAi line and nos-Gal4>UAS-eggpl::GFP line staining with anti-α-Spectrin (green), anti-pMad (red). The scale bar is 10 μm.",
    "ncbi_link": "GFP: 
eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(L) The average number of GSC and CB in nos-Gal4 line, nos-Gal4>UAS-eggpl-RNAi line and nos-Gal4>UAS-eggpl::GFP line on 2 day, 7 day, 14 day and 21 day. Error bars show mean ± SEM, one-way ANOVA, ns indicates no significant difference, *P<0.05, ***P<0.001, n ≥ 72, biological replicates.",
    "ncbi_link": "GFP: 
eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(Q) The statistical analysis of the average number of GSCs and CBs and Cysts in eggpl[1] line. Error bars show mean ± SEM, one-way ANOVA, ns indicates no significant difference, ***P<0.001, n ≥ 104, biological replicates.",
    "ncbi_link": "eggpl: 318223"
  },
  {
    "caption": "(R) The average number of apoptotic germ cells in wild type, nos-Gal4>UAS-eggpl-RNAi line and eggpl[1] line. Error bars show mean ± SEM, one-way ANOVA, ns indicates no significant difference (biological replicates, n=3), and N represents the total number of counted ovarioles.",
    "ncbi_link": "eggpl: 318223
Gal4: 855828
nos: 42297"
  },
  {
    "caption": "(D) Immunofluorescence staining on PGCs of larvae testis tissue. The scale bar is 20 μm. (E) Immunofluorescence staining with anti-α-Spectrin (red) and anti-Vasa (green) on testis from wild type or eggpl[1] flies. The scale bar is 10 μm.",
    "ncbi_link": "eggpl: 318223"
  },
  {
    "caption": "(B) The oviposition of wild type, Nos-Gal4>UAS-eggpl-RNAi and eggpl[1] line over 21 days. Error bars show mean ± SEM, 3 biological replicates (n=3) were performed, and there were 10 female and 5 male adult flies in each biological replicate.",
    "ncbi_link": "eggpl: 318223
Gal4: 855828
Nos: 42297"
  },
  {
    "caption": "(F) Immunofluorescence staining with anti-GFP on germaria from eggpl::GFP knock-in flies with or without feeding fresh yeast paste on day 2-, 7-, 14- and 21. The dotted line indicates the examined area. The scale bar is 10 μm. (G) Quantification of the GFP intensity mean in the eggpl::GFP knock-in line. The central band indicates the median, the box length indicates the interquartile range, and the upper and whisker indicate the maximum and minimum value respectively. The 10 biological replicates (n=10) were performed, one-way ANOVA, ***P<0.001. The dashed line indicates the examined area.",
    "ncbi_link": "GFP: 
eggpl: 318223"
  },
  {
    "caption": "(B) Quantification of the GFP signal in germaria from eggpl::GFP knock-in flies of the indicated genotypes under different conditions. The central band indicates the median, the box length indicates the interquartile range, and the upper and whisker indicate the maximum and minimum value respectively, one-way ANOVA, **P<0.01, ***P<0.001, n = 10, biological replicates.",
    "ncbi_link": "GFP: 
eggpl: 318223"
  },
  {
    "caption": "(b-e) Normalized ratio between luciferase activity bound to beads and present in lysates. The indicated purified GST fusion proteins coupled to beads were incubated with lysates of 293ET cells expressing Nap1, Sintbad or Tank, each fused to luciferase (b)",
    "ncbi_link": "luciferase: 
Nap1: 64343
Tank: 10010
Sintbad: 9755"
  },
  {
    "caption": "(c), lysates of 293ET cells expressing the indicated Nap1 mutants fused to luciferase",
    "ncbi_link": "luciferase: 
Nap1: 64343"
  },
  {
    "caption": "(d), lysates of E. coli expressing Nap1(1-85) fused to luciferase",
    "ncbi_link": "luciferase: 
Nap1: 64343"
  },
  {
    "caption": "(e) lysates of 293ET cells expressing Nap1, NEMO or Optineurin fused to luciferase",
    "ncbi_link": "luciferase: 
Nap1: 64343
NEMO: 8517
Optineurin: 10133"
  },
  {
    "caption": "(c,d) Normalized ratio between luciferase activity bound to beads and present in lysates. The indicated purified GST fusion proteins coupled to beads were incubated with bacterially expressed Nap1(1-85) fused to luciferase. Reactions were complemented with lysates from 293ET cells that had been depleted with the indicated (α-) antibodies (c, top). Immunoblot of lysates after depletion (c, bottom).",
    "ncbi_link": "luciferase: 
Nap1: 64343"
  },
  {
    "caption": "(c,d) Normalized ratio between luciferase activity bound to beads and present in lysates. The indicated purified GST fusion proteins coupled to beads were incubated with bacterially expressed Nap1(1-85) fused to luciferase.Reactions were complemented with the indicated amounts of lysates from E. coli cultures expressing myelin basic protein (MBP) fused to NDP52 (d).",
    "ncbi_link": "luciferase: 
Nap1: 64343"
  },
  {
    "caption": "Percentage of NDP52-positive S. Typhimurium among ubiquitin-coated bacteria, determined by microscopy. HeLa cells transduced with the indicated NDP52 domain-deletion mutants fused to green fluorescent protein were infected with S. Typhimurium and stained for ubiquitin 2 h after infection. ZnF, zinc finger domain. *P 0.01, Student's t-test. Mean and s.d. of triplicate coverslips from two independent experiments; more than 50 ubiquitin-positive bacteria were evaluated per coverslip.",
    "ncbi_link": "NDP52: 10241"
  },
  {
    "caption": "(a) Lysates of cells transfected with the indicated siRNAs blotted for NDP52, TBK1, IKKε and proliferating cell nuclear antigen (PCNA). Control, a nonspecific band detected by the IKKε antibody.",
    "ncbi_link": "IKKε: 9641"
  },
  {
    "caption": "(a-d) Analysis of HeLa cells stably expressing green fluorescent protein-LC3, infected with S. Typhimurium. (a) Confocal micrographs of cells stained 1 h after infection with NDP52 antiserum. Scale bar, 10 μm; arrowheads, bacteria shown in insets. (b) Colocalization of NDP52 with LC3-positive bacteria. (c,d) Counts of LC3-positive S. Typhimurium 1 h after infection in cells transfected with the indicated siRNAs. In c, cells were stained for ubiquitin (Ub); in d, red fluorescence protein (RFP)-expressing S. Typhimurium were used. Means of duplicate counts from four independent experiments; *P 0.05, Student's t-test.",
    "ncbi_link": "NDP52: 10241
LC3: 440738///81631///84557"
  },
  {
    "caption": "(f) Normalized ratio of luciferase-LC3 binding to beads. The indicated purified GST proteins coupled to beads were incubated with bacterially expressed LC3 fused to luciferase and the indicated volumes of lysed E. coli expressing NDP52. Data in a,b,e and f are representative of at least two independent experiments.",
    "ncbi_link": "luciferase: 
LC3: 81631///84557///440738"
  },
  {
    "caption": "Logarithm of the relative viability  after treatment with Resiquimod  (A, n=169), IL4  (B, n=174) stratified by   trisomy 12, and in A, also by IGHV  status. P-values from Student's t-test (two-sided, non-paired). The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "ncbi_link": "IGHV: 3492"
  },
  {
    "caption": "Beeswarm-boxplots of the natural logarithm of the relative viability  of 169 CLL  samples, for (C) fludarabine  + CpG ODN and combinatorial treatments, faceted by IGHV  status and trisomy 12 status. P-values from paired Student's t-test . The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "ncbi_link": "IGHV: 3492"
  },
  {
    "caption": "Beeswarm-boxplots of the natural logarithm of the relative viability  of 169 CLL  samples, for (D) ibrutinib  + IL4  single and combinatorial treatments, faceted by IGHV  status and trisomy 12 status. P-values from paired Student's t-test . The central bar, boxes and whiskers of the plot represent the median, first and third quartiles, and 1.5-times IQR, respectively.",
    "ncbi_link": "IGHV: 3492"
  },
  {
    "caption": "(C) Gene expression for Stat3, Klf2, Esrrb and Tfcp2l1 during EpiSC resetting relative to established mouse ESCs. β-actin serves as an internal control. Mean +/- SEM, n=4 independent experiments. * = p<0.05 Student"s t",
    "ncbi_link": "Esrrb: 26380
Klf2: 16598
Stat3: 20848
Tfcp2l1: 81879"
  },
  {
    "caption": "(C) Left: Flow cytometry profiles of the resetting progression of EpiSCs stably transfected with the Esrrb-T2A-Klf4 construct and cultured in 2i+LIF with DOX for 2 and 4 days, with the indicated fraction of cells sorted for colony formation assay. Since the Venus reporter is under the control of a DOX responsive element, and the emission spectra of Venus and GFP fluorescence overlap, Oct4-GFP reporter could not be fully distinguished from Venus expression. Right: Number of AP+ colonies formed from 250 sorted cells from indicated fractions. Data points represent two technical replicates of one out of two independent experiments",
    "ncbi_link": "Esrrb: 26380
Klf4: 16600"
  },
  {
    "caption": "(C) Left, resetting capacity of Klf2 and Klf4 KO EpiSCs measured by Oct4-GFP+ colony formation at Day 6 of resetting. Data points represent two independent experiments. Right, representative fluorescent and bright field images of wild type and Klf2 KO EpiSCs at Day 6 of resetting in 2i+LIF",
    "ncbi_link": "Klf2: 16598
Klf4: 16600"
  },
  {
    "caption": "(D) Expression of naïve pluripotency, transition and somatic lineage markers in wild type and Klf2 KO EpiSCs during a resetting time course in 2i+LIF. Expression is normalised to wild type EpiSCs in A/F, and β-actin was used as internal control. The values shown correspond to the average expression of three technical replicates from one representative experiment out of two",
    "ncbi_link": "β-actin: 
Klf2: 16598"
  },
  {
    "caption": "(E) Rescue of Klf2 KO EpiSC resetting by forced expression of individual network components measured by Oct4-GFP+ colony formation at Day 6 of resetting in 2i+LIF. Data points represent two independent experiments",
    "ncbi_link": "Klf2: 16598"
  },
  {
    "caption": "(G) EpiSC resetting in 2i+LIF measured by Oct4-GFP+ colony formation after Stat3 siRNA in wild type EpiSCs (left), or Klf4 KO EpiSCs transfected with Tfcp2l1 and Gbx2 siRNAs. n=3 independent experiments in wild type cells (box plots indicate min, median, max), n=2 for Klf4-/- cells (box plots indicate min, mean, max)",
    "ncbi_link": "Gbx2: 14472
Klf4: 16600
Stat3: 20848
Tfcp2l1: 81879"
  },
  {
    "caption": "(H) EpiSC resetting in 2i+LIF measured by Oct4-GFP+ colony formation of Stat3 knockdown EpiSCs transiently transfected with Tfcp2l1, Gbx2 and Klf4. n=4 independent experiments: Student\"s t-test, p-value indicated on plot. Box plots indicate min, median, max. See also Appendix Fi",
    "ncbi_link": "Gbx2: 14472
Klf4: 16600
Stat3: 20848
Tfcp2l1: 81879"
  },
  {
    "caption": "(B) Comparison of predictions (left) and experimental outcome (right) for the potency of additional network factors in OSKM-driven MEF reprogramming in LIF containing medium n=4 independent experiments, except Klf2 and Nanog where n=2 independent experiments. * = p<0.05 Student\"s t-test. n.s. = not significant. Red dashed lines indicate empty vector + OSKM (C) Comparison of predictions (left) and experimental outcome (right) for the potency of additional network factors in OSKM-driven MEF reprogramming in 2i+LIF. n=4 independent experiments, except Klf2 and Nanog where n=2 independent experiments. * = p<0.05 Student\"s t-test. n.s. = not significant. Empty vector + OSKM reprogramming in LIF ('control no 2i') was included as a control for the effect of 2i addition. Red dashed lines indicate empty vector + OSKM control level. Box plots indicate min, median",
    "ncbi_link": "Klf2: 16598
Nanog: 71950"
  },
  {
    "caption": "(D) Recapitulation of the gene activation kinetics during MEF reprogramming. Top, the number of regulation steps required for permanent activation of the indicated gene. Tfcp2l1 and Sall4 are found to activate earlier than Nanog and Esrrb. Bottom, gene expression measured from sorted populations of reprogramming intermediates from O"Malley et al. (",
    "ncbi_link": "Esrrb: 26380
Nanog: 71950
Sall4: 99377
Tfcp2l1: 81879"
  },
  {
    "caption": "Quantitation of resection activity in NBS1∆N cells complemented with wild type (WT) or NBS1 R28A K160M mutant and either mock depleted (siCtrl) or depleted of CtIP (siCtIP). At least 300 cells were assessed per condition. The horizontal line represents a median, the box spans from 25th to 75th percentile and the whiskers from 10th to 90th percentile. Statistical significance was determined using ordinary one-way ANOVA with Tukey's multiple comparison test, **** (p<0.0001).",
    "ncbi_link": "NBS1: 4683
CtIP: 5932"
  },
  {
    "caption": "A. Left: Snapshots of actin  comet tails  assembled in Assembly  conditions: 4.5 µm polystyrene  beads coated with 400 nM Strep-SNAP-WA; 3 µM actin, 6 µM profilin, 90 nM Arp2/3 complex, 15 nM capping protein. Right: Tracking of the comet shown in the snapshots. Time  is encoded in color. B. Left: Snapshots of actin  comet tails  assembled in Disassembly conditions: same as assembly  conditions with 200 nM ADF/cofilin  added. Right: Tracking of the comet  shown in the snapshots. Time  is encoded in color. C. Left: Snapshots of actin  comet tails assembled in Recycling  conditions: Disassembly  conditions with 400 nM Cyclase Associated Protein (CAP) added. Right: Tracking of the comet  shown in the snapshots. Time  is encoded in color.",
    "ncbi_link": "SNAP: "
  },
  {
    "caption": "(A) Mouse embryos were immunostained with anti-neurofilament antibody (blue), showing mesencephalic projection. Dispersed axon projections (arrows point to the area of the superior colliculus) and decreased axon fibers (arrowheads point to the area of the pretectal commissure) were observed in Plcg1f/f;Nes-Cre mice at E11.5 (n = 20). The areas of the superior colliculus is shown magnified in each inset (scale bar = 200 μm)",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(E) Whole-mount immunostaining images show neurofilament (red), netrin-1 (purple), and DCC (green), respectively. An E11.5 Plcg1f/f;Nes-Cre embryo showed shortened dorsal ramus and opthalmic nerves (white and yellow boxes). Scale bar: 200 μm",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(B) Phosphorylation of PLCγ1 on Y783 was decreased after knockdown of the DCC receptor by siRNA (siDcc) (N = 3)",
    "ncbi_link": "Dcc: 13176
DCC receptor: 13176"
  },
  {
    "caption": "(C) Western blot for the NTN1 secretion test. Lane #1: transfection-free lysate, #2: transfection-free supernatant, #3: NTN1-transfected cell lyasate, #3 and #4: NTN-1- transfected supernatant",
    "ncbi_link": "NTN-1: 9423
NTN1: 9423"
  },
  {
    "caption": "(D) Ventral mesencephalic (A9) cultures (daggers) derived from control or Plcg1f/f;Nes-Cre mice, were co-cultured with netrin-1-releasing 293T cell aggregates (asterisks; scale bar = 100 μm). The areas delineated by the white boxes between the mesencephalon tissue and 293T cell aggregates are magnified in the respective insets (n = 4)",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(I) Primary mesencephalic neuron culture in the absence or presence of NTN1-conditioned media (n = 100; scale bar: 500μm)",
    "ncbi_link": "NTN1: 9423"
  },
  {
    "caption": "(H) Representative immunoblot of cultured Plcg1f/f (n = 2, N = 3) and Plcg1f/f;Nes-Cre (n = 2, N = 3) mesencephalic neurons stimulated with conditioned media containing Netrin-1.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(B) Immunohistochemical staining of control and Plcg1 conditional knockout (cKO) sagittal brain sections. The deletion of Plcg1 caused structural changes in SI and OT projections in the Plcg1f/f;Nes-Cre (d) mice compared to the controls (a) (n = 4; scale bar = 1 mm). The areas delineated by the white boxes (insets) are magnified images of the OT (b and e), and the yellow boxes are magnified images of the SI (c and f). (C) Quantification of the axon bundle distribution. Green boxes in (b) and (e) were selected as tegions of interest (ROIs) using the ZEN software (n = 4) (one-way ANOVA, F-value: 118.5745, P**<0.005).",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(F) In situ hybridization of PLCγ1 in mDA neurons (scale bar = 50 μm) (green: TH, violet: DIG-labeled probe).",
    "ncbi_link": "PLCγ1: 18803"
  },
  {
    "caption": "(G) Representative images of the CC axon bundles in control (left) and a Plcg1f/f;Nes-Cre (right) mice (n = 4). The tip of the CC was triangular in the control mouse, but oval in the Plcg1f/f;Nes-Cre mouse. The areas delineated by the white boxes are magnified in the insets (red: neurofilament, green: glial fibrillary acidic protein, blue: Hoechst; scale bar = 1 mm).",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(H) The area of the CC in the Plcg1f/f;Nes-Cre mouse was 36% smaller than that in the control mouse (scale bar = 500 μm) (I) Quantitative comparison of the CC areas in the control and Plcg1f/f;Nes-Cre mice (n = 4; t-test; **p < 0.005). Data are presented as the mean ± s.e.m.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(A) Cumulative histograms based on fractional anisotropy (FA) values. (B), show the CC volume relative to FA values. As FA values increased, the structural (CC volume differences increased between the control and Plcg1f/f;Nes-Cre mice. (n = 4; Shapiro-Wilk and t-test; *p < 0.05). Data are presented as the mean ± s.e.m.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(C), Cumulative histograms based on fractional anisotropy (FA) values. (D), show the number of tensors relative to FA values. As FA values increased, the structural number of tensors) differences increased between the control and Plcg1f/f;Nes-Cre mice. (n = 4; Shapiro-Wilk and t-test; *p < 0.05). Data are presented as the mean ± s.e.m.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "(E) Cumulative histograms based on fractional anisotropy (FA) values. (F) show the CC volume and the number of tensors relative to FA values. As FA values increased, the structural (CC volume and the number of tensors) differences increased between the control and Plcg1f/f;Nes-Cre mice. Depending on the number of tensors, the length in the CC appeared to be shortened (E, F). (n = 4; Shapiro-Wilk and t-test; *p < 0.05). Data are presented as the mean ± s.e.m.",
    "ncbi_link": "Cre: 2777477
Nes: 18008
Plcg1: 18803"
  },
  {
    "caption": "E-G, RT-qPCR measurement of mRNA for (E), Fxr1, (F), Fxr2, (G), Fmr1 during upscaling. n=4 in each condition, Student's T-test *p<0.05.",
    "ncbi_link": "Fmr1: 14265
Fxr1: 14359
Fxr2: 23879"
  },
  {
    "caption": "B, Western blot analysis of total GluA1 expression in Ctrl or Fxr1 overexpression (Fxr1) condition during upscaling (Ctrl/Veh n=5, Ctrl/TTX n=5, Fxr1/Veh n=6, Fxr1/Veh n=6). One way Anova with Dunnett's Multiple Comparison Test ***p<0.001.",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "C, Western blot analysis of total GluA1 expression in Ctrl or Fxr1over condition during downscaling (Ctrl/Veh n=4, Ctrl/TTX n=4, Fxr1/Veh n=4, Fxr1/Veh n=4).",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "D, RT-qPCR measurement of Gria1 mRNA in Ctrl or Fxr1over condition during upscaling (Ctrl/Veh n=3, Ctrl/TTX n=3, Fxr1/Veh n=3, Fxr1/Veh n=3). One way Anova with Bonferroni's Multiple Comparison Test ***p<0.001.",
    "ncbi_link": "Fxr1: 14359
Gria1: 14799"
  },
  {
    "caption": "F, Measurement of relative luciferase signal after co-transfection of different tagged luciferase constructs along with GFP (Ctrl) or GFP-Fxr1 (Fxr1) plasmids. n=5 in each condition, Student's T-test *p<0.05, ***p<0.001.",
    "ncbi_link": "GFP: 
luciferase: 
Fxr1: 14359"
  },
  {
    "caption": "G, Immunostaining for surface GluA1 in GFP (Ctrl) or GFP-Fxr1 (Fxr1 over) infected cultures after treatment with Veh, TTX or BIC for 48h.",
    "ncbi_link": "GFP: 
Fxr1: 14359"
  },
  {
    "caption": "Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from cultured cortical neurons after 48 hours of 1 µM TTX or Veh exposure (E) Fxr1overexpressing neurons (Fxr1/Veh n=10 and Fxr1/TTX n=8)",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from cultured cortical neurons after 48 hours of 1 µM TTX or Veh exposure (F) Gsk3 KO neurons (Gsk3KO/Veh n=10 and Gsk3KO/TTX n=11)",
    "ncbi_link": "Gsk3: 56637"
  },
  {
    "caption": "Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from cultured cortical neurons after 48 hours of 1 µM TTX or Veh exposure (G) Fxr1 KO neurons (Fxr1KO/Veh n=16 and Fxr1KO/TTX n=8). H, A linear fit of Fxr1 KO/Veh and Ctrl/Veh amplitudes. I, The degrees of overlap between Fxr1 KO/Veh and Ctrl/Veh data were assessed using various scaling factors. The largest non-significant p-value was obtained with 1.27 scaling factor. J, Cumulative probability plots of the mEPSCs amplitude of Ctrl/Veh, Fxr1 KO/Veh and Fxr1 KO/Veh divided by scaling factor 1.27, which yielded the maximum overlap with Ctrl/Veh data. ",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "K, Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from cultured cortical Gsk3 and Fxr1 KO neurons after 48 hours of 1 µM TTX or Veh exposure (Gsk3/Fxr1KO/Veh n=8 and Gsk3/Fxr1KO/TTX n=11). L, A linear fit of Gsk3/Fxr1 KO/Veh and Ctrl/Veh amplitudes. M, The degrees of overlap between Gsk3/Fxr1 KO/Veh and Ctrl/Veh data were assessed using various scaling factors. The largest non-significant p-value was obtained with 1.68 scaling factor. N, Cumulative probability plots of the mEPSCs amplitude of Ctrl/Veh, Gsk3/Fxr1 KO/Veh and Gsk3/Fxr1 KO/Veh divided by scaling factor 1.68, which yielded the maximum overlap with Ctrl/Veh data. ",
    "ncbi_link": "Fxr1: 14359
Gsk3: 56637"
  },
  {
    "caption": "A, Hourly distribution of wakefulness (WAKE), slow-wave sleep (SWS) and paradoxical sleep (PS) during a 24-h baseline (BL) recording and a second 24-h starting with 6-h sleep deprivation (SD) (recovery: REC) in Ctrl and Fxr1 overexpressing (Fxr1) mice. Significant Group-by-Hour interactions were found for wakefulness during BL (F23,230 = 1.67, p = 0.046) and REC (F23,230 = 2.83, p = 0.0029), for SWS during BL (F23,230 = 1.66, p = 0.045) and REC (F23,230 = 2.89, p=0.0028), and for PS during REC (F16,160 = 2.54, p=0.0018, Two-way ANOVA Huynh-Feldt corrected, *p<0.05).",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "B, Power spectra for WAKE, SWS, and PS in Ctrl and Fxr1 mice computed between 0.75 and 50 Hz per 0.25-Hz for the full 24-h of BL and REC.",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "C, D, The spectral activity of Fxr1 mice expressed relative to that of Ctrl mice for WAKE, SWS and PS during (C) the 24-h BL and (D) the 24-h REC. A significant difference between groups was found for the frequency band 8 to 11.75 Hz during wakefulness (t = 2.30, p=0.044 Student's T-test *p<0.05).",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "E, Time course of wakefulness spectral activity ratio between low alpha (8.5-10.5 Hz) and low theta (4-6 Hz) during BL and REC in Ctrl and Fxr1 mice. A significant Group-by-Interval interaction was found for REC (F22,220 = 1.96, Two-way ANOVA Huynh-Feldt corrected; *p < 0.05), and also when using BL and REC intervals of the light periods (F16,160 = 3.11, p < 0.01),.",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "F, Time course of SWS relative delta activity during BL and REC in Ctrl and Fxr1 mice. A significant Group-by-Interval interaction was found during REC (F13,130 = 1.89, Two-way ANOVA Huynh-Feldt corrected; *p < 0.05).",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "F-H, RNAseq measurement of mRNA for (F) Fxr1, (G) Fxr2, (H) Fmr1 during SD. n=3 in each condition, Student's T-test *p<0.05.",
    "ncbi_link": "Fmr1: 14265
Fxr1: 14359
Fxr2: 23879"
  },
  {
    "caption": "Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from brain slices of S and SD mice. (C) Fxr1 overexpressing (Fxr1/S n=7 cells/5 mice, Fxr1 over/SD n=9 cells/5 mice)",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "Cumulative probability plots of mEPSCs amplitude (500 events per cell) and representative examples of mEPSCs (left panel) recorded from brain slices of S and SD mice. (D) Gsk3 sKO (Gsk3sKO/S n=6 cells/3 mice, Gsk3sKO/SD n=7 cells/4 mice).",
    "ncbi_link": "Gsk3: 56637"
  },
  {
    "caption": "mEPSC (E) mean amplitude of cortical neurons of S or SD mice. Control neurons (Ctrl/S n=8 cells/4 mice, Ctrl/SD n=8 cells/4 mice), Fxr1 overexpressing (Fxr1/S n=7 cells/5 mice, Fxr1 over/SD n=9 cells/5 mice), and Gsk3 sKO (Gsk3sKO/S n=6 cells/3 mice, Gsk3sKO/SD n=7 cells/4 mice). Student's T-test *p<0.05.",
    "ncbi_link": "Fxr1: 14359
Gsk3: 56637"
  },
  {
    "caption": "F, mEPSC (F) frequency of cortical neurons of S or SD mice. Control neurons (Ctrl/S n=8 cells/4 mice, Ctrl/SD n=8 cells/4 mice), Fxr1 overexpressing (Fxr1/S n=7 cells/5 mice, Fxr1 over/SD n=9 cells/5 mice), and Gsk3 sKO (Gsk3sKO/S n=6 cells/3 mice, Gsk3sKO/SD n=7 cells/4 mice). Student's T-test *p<0.05.",
    "ncbi_link": "Fxr1: 14359
Gsk3: 56637"
  },
  {
    "caption": "H, Summary bar graphs showing rectification index of control (S n=12 cells/5 mice, and SD n=10 cells/5 mice), Fxr1P overexpressing (S n=9 cells/4 mice, and SD n=14 cells/4 mice) and Gsk3 sKO (S n=9 cells/3 mice, and SD n=9 cells/3 mice) neurons. One way ANOVA with Bonferroni's Multiple Comparison *p < 0.05.",
    "ncbi_link": "Fxr1: 14359
Gsk3: 56637"
  },
  {
    "caption": "B, Immunostaining for GFP and HA in Ctrl and Fxr1 mouse brain slices. Arrows indicate presence and arrowheads indicate an absence of GFP tagged Fxr1 granules.",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "G, Heat map showing transcripts that have bidirectional expression changes between Ctrl/S, Ctrl/SD, and Fxr1/SD conditions.",
    "ncbi_link": "Fxr1: 14359"
  },
  {
    "caption": "A-B Clearance of a target with a consensus PAM by direct interference. Overlay of fluorescent and  phase contrast time-lapse images. Presence of the target plasmid  is tracked by its YFP  production (A). Reconstructed lineage traces of the imaged population (A) from induction of the CRISPR-Cas  system over time  (grey) lineages show some variation in plasmid  clearance times  (coloured) (B).",
    "ncbi_link": "Cas: 
CRISPR: "
  },
  {
    "caption": "(A) Expression levels of NAT4 analyzed by qRT-PCR using total RNA extracted from a wild-type (BY4741) and Pste5-NAT4 strain grown in 2% (NCR), or 0.1% glucose (CR). NAT4 levels were normalized to TAF10, whose expression remains unchanged. Error bars, SEM (Standard Error of the Mean) of 3 independent experiments. ** p ≤ 0.01; calculated by unpaired two-tailed Student's t-test.",
    "ncbi_link": "TAF10: 
NAT4: 855091
ste5: 851680"
  },
  {
    "caption": "(B) ChIP analysis performed in BY4741 wild-type, nat4Δ and Pste5-NAT4 strains grown in the same conditions as in (A). Chromatin was immunoprecipitated using an antibody against N-acH4 and analyzed by qRT-PCR using primers for the different rDNA regions. Enrichment was normalized to Histone H4 levels. Error bars, SEM of 3 independent experiments. Statistical significance was determined by unpaired two-tailed Student's t test: * p ≤ 0.05; ** p ≤ 0.01 compared values to wild-type NCR conditions; arrowhead p ≤ 0.05 compared values to wild-type CR conditions",
    "ncbi_link": "nat4: 855091
NAT4: 855091
ste5: 851680"
  },
  {
    "caption": "(C) Replicative lifespan (RLS) for BY4741 wild-type and nat4Δ strains. Values in parenthesis (here and hereafter) indicate mean lifespan. Statistical significance (here and hereafter) was determined by one-way ANOVA test: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(D) Mean RLS for wild-type and nat4∆ strains using different genetic backgrounds. Values outside of parenthesis indicate mean lifespan, while values in parenthesis indicate the number of cells examined.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(E) Mean RLS for BY4741 wild-type and nat4Δ strains under NCR and CR conditions.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(F) Mean RLS for BY4741 wild-type and Pste5-NAT4 strains under NCR and CR conditions.",
    "ncbi_link": "NAT4: 855091
ste5: 851680"
  },
  {
    "caption": "(B) ChIP experiments were performed in SF10 wild-type, nat4∆, NET1-TAP and NET1-TAP nat4∆ strains using an anti-IgG antibody. The enrichment from the antibody was normalized to input. Error bars, SEM of 3 independent experiments. Statistical significance was determined by unpaired two-tailed Student's t test: ** p ≤ 0.01 compared nat4∆ to WT values.",
    "ncbi_link": "nat4: 855091
NET1: 853369"
  },
  {
    "caption": "(C) Quantitative real-time PCR analysis of rDNA copy number for young and old cells in BY4741 wild-type, nat4Δ and fob1Δ strains. Error bars, SEM of 3 independent experiments. Statistical significance was determined by unpaired two-tailed Student's t test: ** p ≤ 0.01 compared to corresponding WT values.",
    "ncbi_link": "fob1: 851688
nat4: 855091"
  },
  {
    "caption": "(D) Polysome profiling analysis performed in BY4741 wild-type and nat4Δ strains. The plots are representative of two independent experiments.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(C) Gene expression analysis of selected upregulated stress-response genes (according to results in 3A) in BY4741 wild-type and nat4∆ strains grown under NCR and CR conditions. Expression levels were normalized to TAF10, whose expression remains unchanged. Error bars, SEM of 3 independent experiments. p-values were obtained comparing results to wild-type under NCR conditions, and calculated by unpaired two-tailed Student's t-test: * p ≤ 0.05; ** p ≤ 0.01.",
    "ncbi_link": "TAF10: 
nat4: 855091"
  },
  {
    "caption": "(D) Gene expression analysis showing fold induction levels (Log2) of selected genes comparing BY4741 wild-type and STE5p-NAT4 strains under NCR (2% glucose) and CR (0.1% glucose) conditions. Expression levels were normalized to TAF10, whose expression remains unchanged.",
    "ncbi_link": "TAF10: 
NAT4: 855091
STE5: 851680"
  },
  {
    "caption": "(A) RLS analysis for BY4741 wild-type and nat4-E186A strains. Values in parenthesis (here and hereafter) indicate mean lifespan. Statistical significance (here and hereafter) was determined by one-way ANOVA test: *** p ≤ 0.001; **** p ≤ 0.0001.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(B) Mean RLS for YSC5106 wild-type, nat4∆ and H4S1D strains.",
    "ncbi_link": "nat4: 855091"
  },
  {
    "caption": "(C) Gene expression analysis of the indicated stress-induced genes in YSC5106 wild-type, nat4∆ and H4S1D strains. Expression levels were normalized to RPP0 whose expression remains unchanged. Error bars, SEM of 3 independent experiments. p-values were obtained by comparing nat4∆ and H4S1D to wild-type values and calculated by unpaired two-tailed Student's t test: * p ≤ 0.05; ** p ≤ 0.01.",
    "ncbi_link": "RPP0: 
H4: 855701///852294
nat4: 855091"
  },
  {
    "caption": "(D) Gene expression analysis of the indicated stress-induced genes in BY4742 wild-type, nat4∆ and nat4∆[hNAA40] strains. Expression levels were normalized to ACT1, whose expression remains unchanged.",
    "ncbi_link": "ACT1: 
NAA40: 79829
nat4: 855091"
  },
  {
    "caption": "(A) RLS analysis for YSC5106 wild-type, nat4∆, H4R3K and double mutant strains. Values in parenthesis indicate mean lifespan. Statistical significance was determined by one-way ANOVA test: **** p ≤ 0.0001.",
    "ncbi_link": "H4: 855701///852294
nat4: 855091"
  },
  {
    "caption": "(B) Gene expression analysis of the indicated stress-induced genes in YSC5106 WT, nat4∆, H4R3K and double mutant strains. Expression levels were normalized to RPP0, whose expression remains unchanged.",
    "ncbi_link": "RPP0: 
H4: 855701///852294
nat4: 855091"
  },
  {
    "caption": "(A) Gene expression analysis of the indicated stress-induced genes in young and old cells isolated from YSC5106 WT, nat4∆ and H4R3K nat4∆ strains. Expression levels were normalized to ACT1, whose expression remains unchanged. Error bars, SEM of 3 independent experiments. P-values were calculated by unpaired two-tailed Student's t test: * p ≤ 0.05 compared to young wild-type; arrowhead p ≤ 0.05 compared to old wild-type.",
    "ncbi_link": "ACT1: 
H4: 855701///852294
nat4: 855091"
  },
  {
    "caption": "(B) RLS analysis for WT, nat4∆, pnc1∆ and double mutant strains in BY4741 genetic background. Values in parenthesis (here and hereafter) indicate mean lifespan. Statistical significance (here and hereafter) was determined by one-way ANOVA test: * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001. ns = non-significant.",
    "ncbi_link": "nat4: 855091
pnc1: 852846"
  },
  {
    "caption": "(C) Mean RLS in BY4741 wild-type, msn2∆ msn4∆ double and msn2∆ msn4∆ nat4∆ triple mutant strains.",
    "ncbi_link": "msn2: 855053
msn4: 853803
nat4: 855091"
  },
  {
    "caption": "(D) Mean RLS in BY4741 wild-type, nat4∆, fob1∆ sir2∆ double and fob1∆ sir2∆ nat4∆ triple mutant strains.",
    "ncbi_link": "fob1: 851688
nat4: 855091
sir2: 851520"
  },
  {
    "caption": "(E) ChIP analysis performed in BY4741 wild-type, nat4Δ and Pste5-NAT4 strains grown under NCR and CR conditions. Chromatin was immunoprecipitated using antibodies against N-acH4 and Histone H4, and analyzed by qRT-PCR with the indicated primers. PNC1-P (Promoter), PNC1-S (Transcriptional Start), PNC1-E (End of gene). The enrichment from the antibody was normalized to Histone H4.",
    "ncbi_link": "nat4: 855091
NAT4: 855091
PNC1: 852846
ste5: 851680"
  },
  {
    "caption": "(B) Absolute number of somatic hypermutations (SHM) in the IGHV, IGKV and IGLV segments of IgA and IgG plasmablast antibody genes sequenced from TB7, TB24 and TB33. The absolute number of sequences analyzed is indicated below the graph. Geometric means with SEM are indicated in grey. SHM means of historic data from sorted CD27+IgA+ or CD27+IgG+ cells from peripheral blood of HD are indicated in red for comparison (Berkowska et al, 2015a; Tiller et al, 2007).",
    "ncbi_link": "IGHV: 3492
IGKV: 3519
IGLV: 3546"
  },
  {
    "caption": "(H) Absolute number of somatic hypermutations (SHM) in the IGHV (IGHA, IGHG and IGHM), IGKV or IGLV segments of sorted anti-HBHAmemory cells from TB patients and HCWs. Geometric means with SEM are indicated in grey. For comparison, red lines indicate the historic SHM means for randomly sorted CD27+IgA+, CD27+IgG+ or CD27+IgM+ cells from peripheral blood of HDs (Berkowska et al, 2015a; Tiller et al, 2007; Tsuiji et al, 2006).",
    "ncbi_link": "IGHA: 3492
IGHG: 3492
IGHV: 3492
IGHM: 3507
IGKV: 3519
IGLV: 3546"
  },
  {
    "caption": "Histological examinations of tumor types in (F) K versus KrasG12D; NanogL/L (KN) Tumor tissues collected form indicated mice analyzed using Haematoxylin Eosin (H&E) staining. Representative H&E images are shown. Scale bar, 500 μm (top), 50 μm (bottom).",
    "ncbi_link": "Kras: 16653
Nanog: 71950"
  },
  {
    "caption": "(G) qPCR analysis of stomach-restricted gene set between KL ADC and KLN mucinous tumor sections (n=3 or 4 per group). Results were shown in a box and whisker plot with the minimum value, first quartile, median, third quartile and maximum value. The box represented the 50% of the central data, with a line inside represented the median. The significance was calculated by two-tailed unpaired Student's t-test with Welch's correction. *p=0.0260 (Hnf4α), *p=0.0275 (Vsig1), *p=0.0122 (Gkn3), *p=0.0324 (Ctse), **p=0.0084 (Onecut2).",
    "ncbi_link": "Hnf4α: 15378"
  },
  {
    "caption": "f alpha-KG does not further extend the lifespan of ogdh-1 RNAi worms, mveh = 21.2 (n = 98), mα-KG = 21.1 (n = 100), P = 0.65 (log-rank test).",
    "ncbi_link": "ogdh-1: 177235"
  },
  {
    "caption": "a-g, Effect of alpha-KG on the lifespan of mutant or RNAi worms. a, atp-2 RNAi, mveh = 22.8 (n = 97), mα-KG = 22.5 (n = 94), P = 0.35; or RNAi control, mveh = 18.6 (n = 94), mα-KG = 23.4 (n = 91), P  0.0001. b, daf-2(e1370), mveh = 38.0 (n = 72), mα-KG = 47.6 (n = 69), P  0.0001. c, eat-2(ad1116), mveh = 22.8 (n = 59), mα-KG = 22.9 (n = 40), P = 0.79. d, let-363 RNAi, mveh = 25.1 (n = 96), mα-KG = 25.7 (n = 74), P = 0.95; or gfp RNAi control, mveh = 20.2 (n = 99), mα-KG = 27.7 (n = 81), P  0.0001. e, daf-16(mu86), mveh = 13.4 (n = 71), mα-KG = 17.4 (n = 72), P  0.0001; or N2, mveh = 13.2 (n = 100), mα-KG = 22.3 (n = 104), P  0.0001. f, pha-4(zu225), mveh = 14.2 (n = 94), mα-KG = 13.5 (n = 109), P = 0.55. g, hif-1(ia4), mveh = 20.5 (n = 85), mα-KG = 26.0 (n = 71), P  0.0001; or N2, mveh = 21.5 (n = 101), mα-KG = 24.6 (n = 102), P  0.0001. P values were determined by the log-rank test. Number of independent experiments: RNAi control (6), atp-2 (2), let-363 (3), N2 (5), daf-2 (2), eat-2 (2), pha-4 (2), daf-16 (2), hif-1 (5).",
    "ncbi_link": "gfp: 
atp-2: 175716
daf-16: 172981
daf-2: 175410
eat-2: 175072
hif-1: 180359
let-363: 172167
pha-4: 180357"
  },
  {
    "caption": "b, Increased autophagy in animals treated with alpha-KG or RNAi for atp-2 or let-363. Photographs were taken at ×100 magnification. c, GFP::LGG-1 puncta quantified using ImageJ (Methods). Data show results of 2-3 independent experiments. Bars indicate the mean. ****P  0.0001; NS, not significant (t-test, two-tailed, two-sample unequal variance).",
    "ncbi_link": "atp-2: 175716
let-363: 172167"
  },
  {
    "caption": "A Representative images and quantification of vacuolar morphology of late meristematic cells. PI (green) and pUBQ10::VAMP711 (yellow) depict cell wall and tonoplast, respectively. Seedlings were treated with DMSO (solvent control) or 5 µM FC (Fusicoccin) for 2.5 h in liquid medium (n=24). Mann Whitney U test (***p < 0.001). Data information: Scale bars: 5 µm.",
    "ncbi_link": "VAMP711: 829347"
  },
  {
    "caption": "C Cell wall and vacuolar membrane was visualized with PI (green) and MDY-64 (yellow). pER8::GFP-SAUR19 seedlings were treated with DMSO (n=60) or 10 µM β-estradiol (n=56) for 6 h in liquid medium. Mann Whitney U test (***p < 0.001). Data information: Scale bars: 5 µm.",
    "ncbi_link": "SAUR19: 831668"
  },
  {
    "caption": "D Left: 3-D cell reconstructions of PI-stained cell wall (red) and BCECF-stained vacuole (green) of late meristematic cells in pER8::GFP-SAUR19 lines. Right: Boxplot depicts vacuolar occupancy of the cell. Seedlings were treated with the solvent control DMSO (n=11) or 10 µM β-estradiol (n=8) for 6 h in liquid medium. Student´s t-test (**p < 0.01). Data information: Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "SAUR19: 831668"
  },
  {
    "caption": "E Cell wall and vacuolar membrane was visualized with PI (green) and pUBQ10::VAMP711 (E) (yellow). Col-0 wild type seedlings were treated for 3 h in liquid medium adjusted to pH 5.7 (n=44) or pH 4.5 (n=40). Mann Whitney U test (***p < 0.001). Data information: Scale bars: 5 µm.",
    "ncbi_link": "VAMP711: 829347"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. PI (green) and MDY-64 (yellow) staining depicts cell wall and vacuolar membrane, respectively. (A) Vacuolar morphology of Col-0 (n=64) and fer-4 (n=60). Mann Whitney U test (***p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. (B) 3-D reconstructions of PI-stained cell wall (red) and BCECF-stained vacuole (green). Boxplot depicts vacuolar occupancy of Col-0 control (n=12) and fer-4 (n=10) mutant cells. Mann Whitney U test (**p < 0.01). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. PI (green) and MDY-64 (yellow) staining depicts cell wall and vacuolar membrane, respectively. (C) Col-0 (n=52) and fer-4 (n=44) seedlings were treated with solvent DMSO or 50 µM EGCG for 22 h on solid medium. Kruskal Wallis test followed by Dunn´s multiple comparison (b: p < 0.05, c: p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. PI (green) and MDY-64 (yellow) staining depicts cell wall and vacuolar membrane, respectively. (D) Col-0 (n=28) and fer-4 (n=28) mutant seedling roots were grown on the surface or into the matrix of 2 % agar-containing solid medium. Kruskal Wallis test followed by Dunn´s multiple comparison (b: p < 0.05, c: p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. PI (green) and MDY-64 (yellow) staining depicts cell wall and vacuolar membrane, respectively. (A) Vacuolar morphology of Col-0 control (n=52) and lrx3/4/5 triple mutants (n=48). Mann Whitney U test (***p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "lrx3: 826964"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. (B) 3-D reconstructions of PI-stained cell wall (red) and BCECF-stained vacuole (green) of late meristematic cells. Boxplot depicts vacuolar occupancy of the cell in Col-0 control (n=11) and lrx3/4/5 (n=10). Student´s t-test (***p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "lrx3: 826964"
  },
  {
    "caption": "Representative images and quantification of vacuolar morphology of late meristematic atrichoblast cells. PI (green) and MDY-64 (yellow) staining depicts cell wall and vacuolar membrane, respectively. (C) Col-0 (n=40-44) and lrx3/4/5 (n=36) seedlings were treated with DMSO or 50 µM EGCG for 22 h on solid medium. Kruskal Wallis test followed by Dunn´s multiple comparison (b: p < 0.01, c: p < 0.001). scale bars: 5 µm. Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "lrx3: 826964"
  },
  {
    "caption": "A Rosette phenotype of 3-weeks-old Col-0, fer-4, lrx3/4/5 and fer-4/lrx3/4/5 (upper panel). Vacuolar morphology (MDY-64-stained) of late meristematic atrichoblast cells of Col-0, fer-4, lrx3/4/5 and fer-4/lrx3/4/5 (lower panel). Scale bars: 1 cm (upper row) and 5 µm (lower row).",
    "ncbi_link": "fer-4: 818622
lrx3: 826964"
  },
  {
    "caption": "B LRR4-HA and RALF1-FLAG were transiently expressed (as indicated by + and -) in Nicotiana benthamiana Immunoprecipitation and subsequent detection of the proteins by western blotting was done as labelled.",
    "ncbi_link": "FLAG: 
HA: 
LRR4: 
RALF1: 839389"
  },
  {
    "caption": "C Relative root length [% of control] of Col-0 (n=11-13 ), lrx3/4/5 (n=9-13 ) and fer-4 (n=11-12) after 3 days of RALF1 treatment. Statistical analyses were performed for each concentration using one-way ANOVA followed by Bonferroni post test (1 µM and 1.25 µM b: p < 0.001; 1.5 µM b: p < 0.05, c: p < 0.001). Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values. Representative experiment is shown.",
    "ncbi_link": "fer-4: 818622
lrx3: 826964"
  },
  {
    "caption": "D Nicotiana benthamiana was transiently transformed with LRR4-HA and NtermFER-FLAG. Immunoprecipitation and subsequent detection of the proteins by western blotting was done as labelled.",
    "ncbi_link": "FER: 
FLAG: 
HA: 
LRR4: "
  },
  {
    "caption": "E Yeast was transformed with either empty plasmids (e / e), NtermFER-FLAG or LRR4-HA with the empty plasmid, or both NtermFER-FLAG and LRR4-HA. Growth of yeast on quadruple drop-out medium was only observed in cells transformed with NtermFER-FLAG and LRR4-HA.",
    "ncbi_link": "FER: 
FLAG: 
HA: 
LRR4: "
  },
  {
    "caption": "A Rosette phenotype of 3-weeks-old Col-0, lrx3/4/5 and 35S::LRR4-cit. Data information: Scale bars: 1 cm",
    "ncbi_link": "cit: 
LRR4: 
lrx3: 826964"
  },
  {
    "caption": "B Representative images and quantification of vacuolar morphology of late meristematic cells of Col-0 and 35S::LRR4-cit. PI (green) and MDY-64 (yellow) staining depict cell wall and vacuolar membrane, respectively. Col-0 (n=36) and 35S::LRR4-cit (n=32-36) seedlings were treated with DMSO or 50 µM EGCG for 22 h on solid medium. Kruskal Wallis test followed by Dunn´s multiple comparison (b: p < 0.05, c: p < 0.001). Data information: 5 µm (B). Boxplots: Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "cit: 
LRR4: "
  },
  {
    "caption": "C Relative root length of Col-0 (n=11-13) and 35S::LRR4-cit (n=11-14) after 3 days of RALF1 treatment. Statistical analyses were performed for each concentration using Student´s t-test (***p < 0.001). Boxplots: Boxplots: Box limits represent 25th and 75th percentile, horizontal line represents median. Whiskers display min. to max. values.",
    "ncbi_link": "cit: 
LRR4: "
  },
  {
    "caption": "D Survival rate  of IFNAR-/- mice infected with different dosages of WNV-poly(A)  (n=5). Data information: Three independent assays were performed for above experiments with similar results and data of one representative data was shown. Scale bars represent 50 μm.",
    "ncbi_link": "IFNAR: 15976///15975"
  },
  {
    "caption": "(F) Rag GTPase knockdown induces TFEB nuclear translocation. HeLa cells stably expressing TFEB-3 × FLAG were infected with lentiviruses encoding Short hairpin (Sh‐) RNAs targeting luciferase (control) or RagC and RagD mRNAs. In all samples, 96 h post infection, cells were left untreated (N=normal media), starved (S=starved media) or treated with Torin 1 (T=Torin 1) for 4 h and then subjected to nuclear/cytosolic fractionation. TFEB localization was detected with a FLAG antibody, whereas tubulin and H3 were used as controls for the cytosolic and nuclear fraction, respectively; levels of S6K phosphorylation were used to test RagC and RagD knockdown efficiency.",
    "ncbi_link": "luciferase: 
RagC: 64121
RagD: 58528"
  },
  {
    "caption": "(G) Loss of mTORC2 does not affect TFEB phosphorylation. Mouse embryonic fibroblasts (MEFs) isolated from Sin1−/− or control embryos (E14.5) were infected with a retrovirus encoding TFEB-3 × FLAG; 48 h post infection, cells were treated with Torin 1 (T) for 4 h where indicated, subjected to nuclear/cytosolic fractionation and immunoblotted for FLAG, tubulin, and H3.",
    "ncbi_link": "Sin1: 227743"
  },
  {
    "caption": "(E) S142 and S211 regulate TFEB localization. FLAGimmunostaining (red) of HeLa cells expressing serine‐to‐alanine mutated versions of TFEB-3 × FLAG. Nuclei were stained with DAPI (blue). Values are means of five fields containing at least 50 transfected cells. Student's t‐test (unpaired) ***P0.001. Scale bars represent 30 μm.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(C) Time‐lapse analysis of Torin 1 treatment in a MEF cell expressing TFEB-GFP. Arrow indicates the time of Torin 1 addition. Yellow arrowheads indicate Torin 1‐induced lysosomal accumulation of TFEB-GFP. Time intervals are in minutes.",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "(G) Torin 1 increases binding of TFEB to mTORC1. HEK‐293T cells that express TFEB-3 × FLAG along with HAGST‐Rap2A or HAGST‐RagsDN were treated with vehicle or with Torin1, lysed and subjected to FLAG immunoprecipitation followed by immunoblotting for mTOR and raptor. FLAG-Metap2 served as negative control.",
    "ncbi_link": "Metap2: 10988"
  },
  {
    "caption": "(H) Immunofluorescence of HEK‐293T cells that express TFEB-3 × FLAG along with Rap2A (top) or the RagsDN mutants (bottom), treated with Torin 1 and stained with antibodies against FLAG and LAMP2 (green and red in the merge, respectively; DAPI is in blue). In all images, scale bars represent 10 μm.",
    "ncbi_link": "Rap2A: 5911
Rags: 58528///64121///10325///10670"
  },
  {
    "caption": "(A-C) Immunofluorescence of HEK‐293T cells that express TFEB-3 × FLAG along with a control GTPase or the indicated Rag mutants. Cells were deprived of amino acids (top) or deprived and then stimulated (bottom) for the indicated times and stained for FLAG and mTOR (green and red in the merge, respectively; DAPI is in blue).",
    "ncbi_link": "GTPase: 
Rag: "
  },
  {
    "caption": "(E, F) Immunofluorescence of HEK‐293T cells that express TFEB-3 × FLAG along with Rap2A (E) or the RagsCA mutants (F), subjected to the indicated treatments and stained with antibodies against FLAG and mTOR (green and red in the merge, respectively; DAPI is in blue).",
    "ncbi_link": "Rap2A: 5911
Rags: 58528///64121///10325///10670"
  },
  {
    "caption": "(A) Chloroquine treatment inhibits mTORC1 activity in primary hepatocytes. Primary hepatocytes isolated from 2‐month‐old Tcfebflox/flox (control) and Tcfebflox/flox;Alb‐Cre(Tcfeb−/−) mice were left untreated, or treated overnight with Torin 1, U0126, or Chloroquine. Subsequently, cells were lysed and protein extracts were immunoblotted with the indicated antibodies.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "(B, C) TFEB mediates the transcriptional response to chloroquine and Torin 1. Quantitative PCR (qPCR) of TFEB target genes in primary hepatocytes from control (flox/flox) and Tcfeb−/− mice. Cells were treated with Chloroquine (left) or Torin 1 (right). The graphs show the relative increased expression in the treated versus the corresponding untreated samples. Values represent means±s.d. of three independent hepatocyte preparations (three mice/genotype). Student's t‐test (two tailed) *P‐value ⩽0.05.",
    "ncbi_link": "Tcfeb: 21425"
  },
  {
    "caption": "E. Fisher's exact test for motif enrichment in TBP and DREF downregulated promoters compared to all expressed promoters. Log2 of the Odds ratio displayed. The dashed line are set at a value of 1 and -1.",
    "ncbi_link": "DREF: 34328
TBP: 37476"
  },
  {
    "caption": "J. qPCR on an auxin treatment time course of TBP and Trf2 dependent genes upon individual depletion of TBP or Trf2 and a double depletion of both. Error bars represent the standard deviation across three biological replicates.",
    "ncbi_link": "TBP: 37476
Trf2: 31773"
  },
  {
    "caption": "E. Luciferase assay in which Gal4 DNA binding domain fusion proteins were recruited to 4xUAS sites upstream of a minimal housekeeping Rps12 promoter. Measurements are normalized to Renilla luciferase (transfection control) and GFP. * denotes proteins activating a housekeeping promoter with a log2FC>1.5 and p-value<0.05, two-tailed student's t-test. Error bars represent standard deviation across four biological replices.",
    "ncbi_link": "luciferase: 
Gal4: 33839
Rps12: 39480"
  },
  {
    "caption": "F,  immunoblotting of NPC1L1 in MCs, MPCs and RCs of  Du145TXR or  MCF-7ADR. G, immunoblotting of NPC1L1 in Du145TXR or  MCF-7ADR cells transfected with siNPC1L1  or siScramble.",
    "ncbi_link": "NPC1L1: 29881"
  },
  {
    "caption": "H-I, colony formation assay and quantification of (H) Du145TXR or (I) MCF-7ADR cells transfected with siNPC1L1 or siScramble followed by treatment with indicated agents. One-way ANOVA was used to analyze statistical differences. Data information: Results are representative of three independent experiments.",
    "ncbi_link": "NPC1L1: 29881"
  },
  {
    "caption": "C,  immunoblot analysis of  NPC1L1 and NRF2 in  Du145TXR or  MCF-7ADR cells transfected with siNFE2L2 or siScramble followed by treatment with the indicated agents for 24 hours. Data information: Results are representative of three independent experiments.",
    "ncbi_link": "NFE2L2: 4780"
  },
  {
    "caption": "F-G, relative luciferase activities  of wild-type (WT) or mutant (MUT) NPC1L1  promoter (-205~-215, #1) reporter constructs in (F) Du145TXR or (G) MCF-7ADR cells treated with indicated agents. Student's t test was used to analyze statistical differences. Mean with ± SD. Data information: Results are representative of three independent experiments.",
    "ncbi_link": "NPC1L1: 29881"
  },
  {
    "caption": "J-K, colony formation assay and quantification of (J) Du145TXR or (K) MCF-7ADR cells transfected with siNFE2L2 or siScramble followed by treatment with the indicated agents. One-way ANOVA was used to analyze statistical differences. Data information: Results are representative of three independent experiments.",
    "ncbi_link": "NFE2L2: 4780"
  },
  {
    "caption": "A. Representative FACS plot (left) showing a mixed-lineage clone with a T-lymphoid (CD25+/CD11b-Gr1-), myeloid (CD11b+Gr1+/CD25-), and biphenotypic (CD11b+Gr1+/CD25+) fraction derived from a single Myc/Bcl2-transformed DN2cell grown on 1:1 OP9:OP9-Dll1 co-culture with lineage-promiscuous cytokines IL-2, IL-3, IL-6, IL-7, SCF,GM-CSF, Flt3. Morphology of the indicated flow-sorted cell fractions was analyzed by Giemsa staining (right).",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "B. Phenotype frequencies of clones from Myc/Bcl2-transformed single cells (grown and phenotyped as mentioned in A). Analyzed were 31 clones from LSKs, 107 from GMPs and 28 from DN2 cells.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "C. Cumulative survival of 31±2 and 27±6 days of mice that received 5104 to 5105 T-lymphoid cells or myeloid cells, respectively, that were flow-sorted from mixed Myc/Bcl2+ DN2-derived clones. The summarized data are from 3 mice injected with the T-lymphoid and 4 mice injected with the myeloid fraction of two different clones.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "D. Representative FACS plots demonstrating predominant outgrowth of myeloid clones from single Myc/Bcl2-transformed LSK or GMPcells on OP9:OP9-Dll1 co-cultures.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "E. (top panels) Serial replating of Myc-Bcl2+DN2 cells in methylcellulose generated myeloid clones with stable genomic reassembly of the Dβ1 TCR locus in vitro (gel: left two lanes). Upon transplantation, the same clones induced myeloid leukemia that retained the initial rearrangement in vivo (gel: right two lanes) as assessed by nested PCR. GL = germline. (bottom panels) Methylcellulose-based replating of Myc-Bcl2+GMPs generated myeloid clones that exclusively displayed the TCRß locus in germline configuration.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869
Dβ1 TCR: 21577
TCRß: 21577"
  },
  {
    "caption": "F. Cumulative survival of mice that received 106cells of TCRβ-rearranged myeloid DN2-derived clones leading to death within 33±4 days after transplantation. Two DN2 clones were transplanted into 5 recipient mice.",
    "ncbi_link": "TCRβ: 21577"
  },
  {
    "caption": "A. Representative FACS plots of spleens from leukemic recipient mice that had received LSK, GMP or DN2 cell grafts immediately after retroviral Myc/Bcl2 transduction. Numbers indicate frequencies (%) of CD45.2 donor cells within the indicated gates summarizing the mean±SEM of at least 8 recipients per group from a total of 10 independent experiments.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "B. Cumulative survival of mice that received 2104 to 2105 freshly Myc/Bcl2-transduced LSK, GMP or DN2 cells; Graph shows n=11 Myc-Bcl2+LSK-, n=14 DN2-, and n=8 GMP-transplanted animals.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "C. Histological spleen sections of Myc-Bcl2+LSK-, GMP- or DN2-transplanted mice displaying myeloperoxidasestaining. Leukemic cell engraftment in spleens ranged from 75.1%-95.5%.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "D. Multiplex quantitative RT-PCR demonstrating strong expression of PU.1 in the myeloid (M3L: CD11b+Gr1+/CD3-CD4-CD8-) and biphenotypic T/myeloid (BL: CD11b+Gr1+/CD3+CD4+CD8+) fractions but not in the T-lymphoid (TL: CD11b-Gr1-/CD3+CD4+CD8+) fraction that were flow-sorted from diseased Myc-Bcl2+DN2-transplanted mice. Myeloid progeny of Myc/Bcl2+GMP-transplanted or T-lymphoid progeny of Myc/Bcl2+DN3-transplanted animals as well as healthy thymocytes (Thy) and BM cells from WT mice served as controls. Results are shown as fold over actin transcripts.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869
PU.1: 20375"
  },
  {
    "caption": "E. D-J rearrangement PCR of flow-sorted T-lymphoid (TL), biphenotypic (BL) and myeloid (ML) fractions of donor splenocytes of a diseased Myc/Bcl2+DN2-transplanted mouse. All three fractions revealed a stable genomic reassembly of the Dβ1 TCR locus (Dβ1Jβ1.5) demonstrating clonality in DN2 leukemia. thy = thymus.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "F. FACS plot of diseased intrathymic grafts (CD45.2-gated), demonstrating that Myc/Bcl2+DN2 cells could produce multi-lineage leukemia within a T-cell supporting environment; Myc/Bcl2+GMPs remained myeloid restricted under these conditions. Numbers indicate cell frequencies within the gates (mean±SEM) representing six independent experiments.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "A. GSEA demonstrates that Myc/Bcl2+DN2-derived myeloid blasts were significantly (FDR >0.05) enriched for expression of a pan-dendritic cell gene set. Gene sets were published in (Schonheit et al., 2013).",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "D. GSEA demonstrates significant enrichment of a normal DN2-specific gene set (see methods section) in the Myc/Bcl2+DN2-derived myeloid blasts.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "A. Western blot illustrating abundant Bcl11b and Gata3protein expression in Myc/Bcl2+DN2- but not LSK- or GMP-derived blasts. Thymus (Thy) and bone marrow (BM) extracts from healthy WT mice served as controls. Detection of α-tubulin or valosin-containing protein (VCP) ensured comparable loading.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "B,C. Proliferation assays illustrating growth of Myc/Bcl2+ DN2- (B) or GMP-derived (C) blasts after lentiviral transduction with the indicated shRNAs. The shRNA-transduced cells were flow-sorted based on co-expression of the RFP-reporter and seeded on OP9/OP9Dll1 1:1 layers. Growing cells were RFP-sorted for 3 rounds within 21 days of culture and percent growth was calculated over the initially seeded cell number in relation to the Luc control. Shown are results of 4 independent experiments with cells from 4 different DN2- and 3 different GMP-leukemic animals. Luc= control shRNA targeting luciferase (Suzuki et al., 2003). At least 2 different shRNAs were used against Bcl11b or Gata3 as indicated. * = p≤0.05, Student's t-test.",
    "ncbi_link": "luciferase: 
Bcl11b: 58208
Bcl2: 12043
Gata3: 14462
Myc: 17869"
  },
  {
    "caption": "D. Representative FACS plots showing CD45.2-donor splenocytes of a secondary (CD45.1) recipient 23 weeks after transplantation with 4103RFP+Myc-Bcl2+DN2-leukemia blasts carrying the indicated shRNAs. Luc: luciferase control shRNA. The data are representative of 2 Gata3, 4 Bcl11b, and 2 luciferase shRNA-transplanted animals.",
    "ncbi_link": "luciferase: 
Bcl11b: 58208
Bcl2: 12043
Gata3: 14462
Myc: 17869"
  },
  {
    "caption": "A. Representative FACS plots of splenocytes from diseased secondary recipients that were transplanted with 104 to 105 flow-sorted myeloid leukemia blasts (ML: CD11b+Gr1+/CD3-CD4-CD8-) from sick primary Myc/Bcl2+LSK-, GMP- or DN2-transplanted mice. Cell percentages in indicated gates are shown.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "B. Table summarizing the phenotype frequencies within the spleens of secondary recipients that were retransplanted with Myc/Bcl2+LSK-, GMP- or DN2-derived myeloid blasts as described in A. T-lymphoid leukemia: (TL: CD11b-Gr1-/CD3+CD4+CD8+), biphenotypic leukemia: BL (CD11b+Gr1+/CD3+CD4+CD8+), myeloid leukemia: ML (CD11b+Gr1+/CD3-CD4-CD8-). Numbers before the dash represent mice holding the indicated leukemia fraction; numbers after the dash indicate the total mouse count analyzed.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "C. Single myeloid blasts from 4 different Myc/bcl2+ DN2-derived leukemias were flow-sorted from transplanted mice and grown on irradiated OP9:OP9DL1 stroma. The clones were analyzed at two different time points. FACS plots of two representative clones, one with strong (top) and one with weak (bottom) lineage switching potential are shown.",
    "ncbi_link": "bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "E. FACS plot of DN2-derived primary leukemic cells transduced with a retrovirus carrying GFP alone or GFP together with PU.1 as a bicistronic RNA. The transduced cells were grown on OP9/OP9Dll1 1:1 layer for 8-13 days and analyzed using a GFP-gate. The data are representative of 3 different experiments with similar outcome.",
    "ncbi_link": "PU.1: 20375"
  },
  {
    "caption": "A. Heat map depicting all human AML samples from the Haferlach study (Haferlach et al., 2010) whose transcriptomes resembled DN2-leukemia by a Spearman's rank correlation coefficient ≥ 0.5. The top 100 up- and downregulated gene signature of Myc/Bcl2+DN2-derived myeloid blasts was applied (see also Figure 3B).",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "C,E. GSEA confirming enrichment of the Myc/Bcl2+DN2-derived myeloid blast top 100 UP (C) and pan-DC (Schonheit et al., 2013) (E) gene signatures in the human FAB M2 DN2-like AML samples as compared to all residual M2 AMLs from the Verhaak study (Verhaak et al., 2009). D. Relative transcript levels of the T cell receptor alpha locus (TRAC) in human DN2-like M2 AML compared to residual M2 AML patient samples from the Verhaak study (Wilcoxon rank-sum test, **=p≤0.01).",
    "ncbi_link": "Bcl2: 12043
Myc: 17869
TRAC: 6955"
  },
  {
    "caption": "A. Survival assay of Myc/Bcl2+GMP- and DN2-derived leukemia cells that were isolated from diseased mice and treated for 24 h with 0.15 μM daunorubicine or 1 μM doxorubicine in liquid culture. Cell death was measured by FACS of 7-AAD+cells and was normalized to the solvent controls. The graphs show the mean+SEM of three different DN2- and five GMP-leukemias. **=p≤0.01.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "E. Percent cell growth of 5 different DN2-derived leukemic cell lines transduced with 2 different shRNA constructs targeting Jak2. The cells were sorted for the GFP or YFP reporter and normalized to the control shRNA targeting the lacZ gene (lacZ). Four of five DN2-derived leukemias show reduced growth with both shRNAs after the second round of sorting within 8 days in culture. The lacZ control was set to 100%.",
    "ncbi_link": "lacZ: 
Jak2: 16452"
  },
  {
    "caption": "F. Proliferation curves of 3 Myc/Bcl2+ DN2- and 3 GMP-derived leukemia lines during treatment with 0.5 μM ruxolitinib. 1.5105 cells were seeded in culture and counted at the indicated time points. Results are shown as fold growth of the starting cell number which was set to 1. *=p≤0.05, **=p≤0.01, Student's t-test.",
    "ncbi_link": "Bcl2: 12043
Myc: 17869"
  },
  {
    "caption": "(A) Representative images of whole brains from wild-type (WT) and hFOXM1f/+-NesCre (hFOXM1-cKI) mice pups at P0. Scale bar,100μm. (B) Quantification of cortical width and length at P0 (WT n=7; hFOXM1-cKI n=7; two-tailed unpaired t-test, P= 0.0361for width, P= 0.2866 for length). (C) Quantification of brain/body weight at P0 (WT n=9; hFOXM1-cKI n=9; two-tailed unpaired t-test, P= 0.0004). (D) Quantification of cortex thickness at P0 (WT n=7; hFOXM1-cKI n=11; two-tailed unpaired t-test, P= 0.0002). (E)",
    "ncbi_link": "Cre: 2777477
FOXM1: 2305
Nes: 18008"
  },
  {
    "caption": "(E) Staining for Satb2 and Ctip2 in P0 WT and hFOXM1-cKI mice folding structure. Asterisks indicate gyrus and arrows indicate sulcus structures. A1, A2, B1and B2 (DAPI) are high-magnification images. Scale bars, 200μm(left); 100μm(right). (F) Quantification of GI of WT and hFOXM1-cKI mice pups at P0. The quantification of the GI was analyzed in pre-selected hFOXM1-cKI mice with folding. (n = 6 each group; two-tailed u unpaired t-test, P= 0.0010).",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(H) Graph shows the number of Satb2+cells in 4×104µm2 at P0 (WT n=5; hFOXM1-cKI n=5; two-tailed unpaired t-test, P= 0.0086). (I) Graph shows the number of Ctip2 +cells in 4×104µm2 at P0 (WT n=5; hFOXM1-cKI n=5; two-tailed unpaired t-test, P= 0.0025). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(K) Staining for Cux1 in P0 WT and hFOXM1-cKI mice. Scale bar,100μm. (I) Graph shows the number of Cux1+cells in 4×104µm2 at P0 (WT n=3; hFOXM1-cKI n=3; two-tailed unpaired t-test, P= 0.0451). D",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(A) Staining for Pax6 and p-Vim in E15 WT and hFOXM1-cKI mice. The right A and B are high-magnification images. Arrows indicate double positive of Pax6+ p-Vim+ cells with cells with a basal process (arrowheads). Scale bars, 50μm (left); 5μm (right). (B) Graph shows the percentage of Pax6+ cells in enlarged SVZ (n = 6 each group; two-tailed unpaired t-test, P=0.0002). (C) Graph shows the number of Pax6+ p-Vim+ cells in 4x10^4 μm2 in enlarged SVZ (n = 6 each group; two-tailed unpaired t-test, P=0.0003). (D",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(D) Staining for Sox2 in E15 WT and hFOXM1-cKI mice. Scale bar, 50μm. (E) Graph shows the number of Sox2+ cells in 4x104 μm2 in enlarged SVZ (WT n=3; hFOXM1-cKI n=4; two-tailed unpaired t-test, P=0.0292). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(F) Staining for Tbr2 in E15 WT and hFOXM1-cKI mice. Scale bar, 50μm. (G) Graph shows the number of Tbr2+ cells in 4x104 μm2 in enlarged SVZ (WT n=6; hFOXM1-cKI n=9; two-tailed unpaired t-test, P=0.0003). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(H) Staining for HOPX in E15 WT and hFOXM1-cKI mice. Scale bar, 50μm. (I) Graph shows the number of HOPX+ cells in 4×104 μm2 in enlarged SVZ (n = 4 each group; two-tailed unpaired t-test, P= 0.0044). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(J) Staining for Ki67 in E15 WT and hFOXM1-cKI mice. Scale bar, 50μm.",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(L) The experimental scheme and staining for BrdU and EdU in E15 WT and hFOXM1-cKI mice. White arrows represent BrdU and EdU double-positive cells. Scale bars, 50μm(left);20μm(right). (M) Graph shows the percentage of BrdU and EdU double-positive cells in E15 WT and hFOXM1-cKI mice (n = 6 each group; two-tailed unpaired t-test, P=0.0413). D",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(B) Cell immunostaining for HOPX in control, hFOXM1-FL and mutants in mice primary neural progenitors 3 days following lentiviral infection. White arrows represent GFP HOPX double-positive cells. Scale bar, 50μm. (C) Graph shows the percentage of HOPX+ cells among GFP+ cells (Control n=3; hFOXM1-FL n=6; hFLΔexon9 n=5; one-way ANOVA, F (2, 12) = 29.13, control vs. hFOXM1, P=0.0002; control vs. hFOXM1Δexon9, P=0.9080). (D) Cell immunostaining for HOPX in control, mFoxm1-FL and mutants in mice primary neural progenitors 3 days following lentiviral infection. White arrows represent GFP HOPX double-positive cells. Scale bar, 50μm. (E) (E) Graph shows the percentage of HOPX+ cells among GFP+ cells (Control n=4; mFoxm1-FL n=6; mFL+h exon9 n=4; one-way ANOVA, F (2, 11) = 8.163, control vs. mFoxm1, P= 0.4747, control vs. mFoxm1+h exon9, P= 0.0066). (",
    "ncbi_link": "FOXM1: 2305
Foxm1: 14235"
  },
  {
    "caption": "(C) Volcano plots shows the gene expression states. The yellow dots are the up-regulated genes, and the blue dots are the down-regulated genes. The Lin28a gene (red dot) is significantly up-regulated.",
    "ncbi_link": "Lin28a: 83557"
  },
  {
    "caption": "(D) Western blot analysis for Lin28a in cortex of E15 WT and hFOXM1-cKI mice. β-actin was detected as loading control.",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(I) LIN28A-shRNA1 rescues the neuronal progenitor cell increase in hFOXM1-cKI mice. Brain slice staining for Sox2 two days after IUE at E13. Scale bar, 50μm. (J) Graph shows the percentage of Sox2+ cells among GFP+ cells (n=3 each group; one-way A",
    "ncbi_link": "FOXM1: 2305
LIN28A: 79727"
  },
  {
    "caption": "(B) Representative cases of FOXM1+/+ and FOXM1-/- NPCs clones. Scale bar, 20μm. (C) Graph shows the number of cells per clone in FOXM1+/+ and FOXM1-/- human NPCs (FOXM1+/+ n=12; FOXM1-/- n=13; at least three biological replicates. two-tailed unpaired t-test, P= 0.0014). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(D) Overexpression of FOXM1 or LIN28A rescues the human neural progenitor cell reduction in FOXM1-/- cell lines. Western blot analysis for SOX2, PAX6 and HOPX. β-actin was detected as loading control. (E) Statistics of relative intensity of SOX2, PAX6 and HOPX (PAX6: n=3 biological replicates; one-way ANOVA, F (2,6) = 8.716, FOXM1-/-(Control) vs. FOXM1-/-(hFOXM1), P= 0.0173, FOXM1+/+(Control) vs. FOXM1-/-(hFOXM1), P= 0.0476. SOX2: n=5 biological replicates; one-way ANOVA, F (2, 12) = 14.72, FOXM1+/+(Control) vs. FOXM1-/-(Control), P= 0.0015, FOXM1+/+(Control) vs. FOXM1-/-(hFOXM1), P=0.9906. HOPX: n=4 biological replicates, one-way ANOVA F (2, 9) = 25.28, FOXM1+/+(Control) vs. FOXM1-/- (Control), P= 0.0018, FOXM1+/+(Control) vs. FOXM1-/-(hFOXM1), P= 0.2211). (",
    "ncbi_link": "FOXM1: 2305"
  },
  {
    "caption": "(C) Scatter plots of the average diffusion coefficient (µm2 s-1) single-molecule mobility of SV2Awt-pH/At565nb and SV2AT84A-pH/565nb in the control condition (high K+; Ctrl) and following treatment with 100 pM BoNT/Aiwt-At647N or BoNT/AiSV2-At647N (supplemented in high K+). (D) Scatter plots of the average diffusion coefficient (µm2 s-1) single-molecule mobility of Syt1wt-pH/At565nb, Syt1K362A,K328A-pH/565nb and Syt1K52A-pH/At565nb in the control condition (high K+; Ctrl) and following treatment with 100 pM BoNT/Aiwt-At647N (supplemented in high K+).",
    "ncbi_link": "pH: 
SV2A: 9900
Syt1: 25716"
  },
  {
    "caption": "(A) Representative confocal Z-stack sum projections of neurons transduced with TagBFP2-expressing (blue) control (ctrl; non-targeting sgRNA) and CRISPRi Syt1 KD (Syt1 sgRNA1-3) lentiviruses. Neurons were treated for 30 min with 10 units of AbobotulinumtoxinA, and immunostained for endogenous Syt1 (yellow) and BoNT/A-cleaved SNAP-25 (SNAP-25/A; magenta). Boxed regions (i-iv) are magnified on the right, with neuronal somas outlined by dashed lines for clarity. B, C Quantification of mean fluorescence intensity (MFI) of endogenous (B) Syt1, and (C) cleaved SNAP-25 (SNAP-25/A), in control and Syt1 sgRNA1-3 KD neurons following AbobotulinumtoxinA treatment. (B-C) n = 21 technical replicates/ condition from 2 independent biological replicates. Statistical significance was assessed using a non-parametric Kruskal-Wallis multiple comparison test",
    "ncbi_link": "BFP2: 
CRISPR: 
Syt1: 25716"
  },
  {
    "caption": "H, I Quantification of (H) Syt1 and (I) SNAP-25/A MFI in non-transduced neurons (neurons negative for TagBFP2) with and without pLenti6.3-Syt1wt-pH expression following AbobotulinumtoxinA treatment (10 units, 30 min.) n = 3 technical replicates/ condition from one biological experiment.",
    "ncbi_link": "pH: 
Syt1: 25716"
  },
  {
    "caption": "(A) Representative patch-clamp spontaneous miniature inhibitory postsynaptic current (mPSC) recordings in naïve neurons, and in control (non-targeting) and Syt1 KD (CRISPRi sgRNA1) neurons following a 30 min treatment with AbobotulinumtoxinA (10 units). B, C Quantification of mPSC (B) peak amplitudes and (C) frequencies for indicated conditions. Error bars are shown as standard error of the mean (±SEM). N = 5-12 technical replicates/ condition from 2 independent biological replicates in (B, C) statistical significance was assessed using a non-parametric Kruskal-Wallis multiple comparison test (B), an ordinary one-way ANOVA multiple comparison test (C)",
    "ncbi_link": "CRISPR: 
Syt1: 25716"
  },
  {
    "caption": "(D) EM analysis of endocytosed BoNT/Aiwt-HRP following lentiviral control (ctrl; non-targeting sgRNA) and Syt1 sgRNA1 CRISPRi KD transduction. HRP precipitate in synaptic vesicles (SVs; arrowheads) and tubular structures (arrows) in presynapses (Ps) are indicated. The postsynaptic density is marked with an asterisk. (E) Percentage of total BoNT/Aiwt-HRP localized in SVs, endo/lysosomes (E), tubular structures (T), multivesicular bodies (MVB), structures resembling autophagosomes (AP) and on the plasma membrane (PM) in the indicated conditions. n = 56 regions of interest/ condition from 2 independent biological replicates (E) two-way ANOVA multiple comparison test (E).",
    "ncbi_link": "CRISPR: 
Syt1: 25716"
  },
  {
    "caption": "(a, b) Isolated acini from wild-type (WT) and Trpml1-/- mice (ML1-/-) were used to determine the frequency of Ca2+ oscillations in response to stimulation with 3 and 10 pM CCK (a) and the response to high concentrations of CCK (b). The average frequency from multiple experiments is given in the columns as mean±s.e.m in (a). The traces and columns in (b) show the mean±s.e.m of 3 experiments each includes 4-6 acini composed of 6-10 cells.",
    "ncbi_link": "ML1: 94178
Trpml1: 94178"
  },
  {
    "caption": "Panel (a) shows example TEM ultrastructure images obtained from male and female mice pancreas and the columns shows the granules size distribution. Granules size was analyzed in at least 10 images from 3 wild-type and 5 Trpml1-/- mice.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(b) Fixed acini were co-stained with Amylase (granules) and LAMP1 (lysosomes) and the fold overlap was calculated from 14 and 11 images obtained from 3 wild-type and 3 Trpml1-/- mice, respectively.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(c) Live wild-type and Trpml1-/- acini were labeled with mitotracker (green) and lysotracker (red). The panels show the merged green, red and DIC images. The large vesicles are marked by white arrows and shown at higher magnification in the inserts. The overlap between lysosomes and granules was determined by ImageJ (see methods). The results are from 14 wild-type and 30 Trpml1-/- acini each comprising 3-7 cells and obtained from 3 wild-type and 4 Trpml1-/- mice.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(e) Enhanced exocytosis of the lysosomal acid phosphatase by Trpml1-/-acini stimulated with 100 pM CCK. The results are the mean±s.e.m of 3 experiments with acini obtained from 3 wild-type and 3 Trpml1-/-mice.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(a) Isolated acini from wild-type (black) and Trpml1-/- mice (red) loaded with Fura2 were used to determine [Ca2+]i in response to stimulation with 100 µM carbachol. The traces are the mean±s.e.m. of 6 acinar clusters. Similar results were obtained in 3 experiments.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(b, c) Saliva was collected from wild-type (black) and Trpml1-/- mice (red) injected I.P. with 10 mg/kg pilocarpine (b) or 1 mg/kg pilocarpine and 0.6 mg/kg isoproterenol (c) over 20-40 min to stimulate fluid secretion by pilocarpine and amylase secretion by isoproterenol. Each condition used 4-5 mice from each like and the results are given as the mean±s.e.m.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(e, f) Isolated acini from the parotid glands of wild-type (black) or Trpml1-/- mice (red) were used to measure amylase secretion in response to 50 nM isoproterenol for the indicated times (e) and the indicated isoproterenol concentrations during 30 min stimulation (f). The results are the mean±s.e.m obtained from two mice of each line.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(a) shows example TEM images and (b) shows the granules size distribution in parotid glands determined from 10 images obtained from 3 wild-type mice and 14 images obtained from 4 Trpml1-/- mice.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(d) Acini isolated from the parotid glands of wild-type and Trpml1-/- mice were incubated with mitotracker (green) and lysotracker. The large vesicles in the secretory granules/lysosomal area are marked by white arrows. The average number of enlarged profiles is given in the columns and obtained from 3 acinar preparations of each line.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(e) Shown is the time course (left panel) and averaged 10 min secretion (columns) of the lysosomal marker acid phosphatase in the saliva collected from wild-type (black) and Trpml1-/- mice (red) stimulated with 1 mg/kg pilocarpine and 0.6 mg/kg isoproterenol. The mean±s.e.m is from 4 mice of each line.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(a, b) example traces of mEPSCs recorded from wild-type (a) and Trpml1-/-(b) micebrain slices as detailed in Methods. The lower traces in each panel show the portion of the traces marked by dotted boxes in an expanded time scale. (c) histogram distribution of the events at each mEPSC. The lower columns show the distribution of the higher amplitude mEPSCs. (d) the frequency of mEPSCs in each line. The results in (c, b) are the mean±s.e.m of 8 experiments each obtained from 4 mice of each line.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(e) the mean±s.e.m of the Ca2+ signal in response to depolarization with 30 mM KCl of 6 and 5 experiments with wild-type and Trpml1-/- slices, respectively.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(a) example TEM images of synapses in wild-type and Trpml1-/-micebraincortex. (b) the distribution of synaptic vesicle size determined in 10 and 14 images obtained from 3 wild-type and 3 Trpml1-/-mice, respectively. (c) example TEM images at low magnification of wild-type and Trpml1-/-micebraincortical slices with the dark PSD profiles marked by white arrows. (d) average number of PSD/µm2 analyzed in at least 10 images obtained from 3 mice of each line.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(e) Glutamate levels and secretion by cultured cerebral cortical neurons. Total glutamate measured in non-stimulated wild-type (black) and Trpml1-/- (green) neurons and neurons stimulated by depolarization with 30 mM KCl (blue and red).",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "(f) Rescue of glutamate levels and secretion by expression of TRPML1 in cultured cerebral cortical neurons. Total glutamate measured in non-stimulated Trpml1-/- neurons (green) and Trpml1-/- neurons transfected with TRPML1 (black) and untransfected (red) and TRPML1-transfected (clue) Trpml1-/- neurons stimulated by depolarization with 30 mM KCl.",
    "ncbi_link": "TRPML1: 94178
Trpml1: 94178"
  },
  {
    "caption": "(g) averaged Co-IP of SNAP25 and VAMP2 in three brain regions of wild-type and Trpml1-/- mice. The images of all blots are given in Extended view Figure E4.",
    "ncbi_link": "Trpml1: 94178"
  },
  {
    "caption": "B-C. Wound healing assays were performed using IBIDI® chambers to evaluate the role of the AhR  on cell migration. Images of the wound  were captured using an Axio Vert.A1 inverted microscope (Carl Zeiss®) at 5x magnification. The histogram represents the mean ± s.d. Wound  closure was determined by measuring the distance between the edges of the wound  at time  0 and 15 h (n = 3 independent technical experiments for each cell lines or conditions) and compared using unpaired t-tests with the Sidak-Bonferroni method. B. Results obtained with BRAFi-sensitive or resistant SK28  cells KO for the AhR  in the absence of treatment. (n = 3 independent technical experiments for each cell lines). C. Results obtained for the migration assay  (0 to 15 h) for SK28  R cells KO or not for the AhR  after treatment or not with 10 μM CH-223191. (n = 3 independent technical experiments for each cell lines or conditions, mean ± s.d.). Statistical analysis using unpaired t-tests with the Sidak-Bonferroni method has been performed between the mean of the 3 independent experiments.",
    "ncbi_link": "AhR: 196"
  },
  {
    "caption": "D. Three-dimensional spheroid growth  of BRAFi-sensitive or resistant SK28  cells KO before or after knockout of AhR  by CRISPR/Cas9  in the absence of treatment. Images were captured four days after implantation of the spheroids  into collagen  gel. (n = 4 independent technical experiments, mean ± s.d. E. Three-dimensional spheroid growth  of BRAFi-resistant SK28  cells KO before or after knockout of AhR  by CRISPR/Cas9  after daily treatment with the specific AhR  inhibitor CH-223191 (5 μM) for one week or in the absence of treatment. Images were captured four days after implantation of the spheroids  into collagen  gel. (n = 3 independent technical experiments, mean ± s.d.). Statistical analysis using unpaired t-tests method has been performed with the Sidak-Bonferroni method, (p<0.01 ##, **; p<0.001 ###,***).",
    "ncbi_link": "CRISPR: 
AhR: 196
Cas9: 69900935"
  },
  {
    "caption": "A. AhR  Protein levels in 501Mel  CTR cells and those transduced with sgRNA targeting AhR  (#1, #2) were analyzed by western blotting.",
    "ncbi_link": "AhR: 196"
  },
  {
    "caption": "D. AhR  Protein levels in SK28R WT, KO, and KO CA-AhR  cells were analyzed by western blotting.",
    "ncbi_link": "AhR: 196"
  },
  {
    "caption": "F. Three-dimensional spheroid growth  of SK28  cells KO or not for AhR  by CRISPR/Cas9  and rescued by the constitutive active form of AhR  (KO CA-AhR). Images were captured four days after spheroid implantation (n = 3 independent technical experiments, mean ± s.d.). Comparisons were performed using unpaired t-tests with the Sidak-Bonferroni method.",
    "ncbi_link": "CRISPR: 
AhR: 196
Cas9: 69900935"
  },
  {
    "caption": "C. Protein levels of the AhR, p-SRC  (Y416), SRC, p-FAK  (Y576/577), and FAK  in the SK28R cell line KO or not for AhR  by CRISPR/Cas9  or after rescue with the activated-form of the AhR  (CA-AhR).",
    "ncbi_link": "CRISPR: 
AhR: 196
Cas9: 69900935"
  },
  {
    "caption": "(a) Kaplan-Meier survival plot of cohorts of induced Vil Apc, Vil Apc Huwe1het and Vil Apc Huwe1hom mice. Deletion of Huwe1 led to a significant reduction in survival of these animals (Vil Apc vs Vil Apc Huwe1het / Vil Apc Huwe1hom, Log Rank, p < 0.001, n ≥ 10).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(b) Wholemount isolation of small intestines from Vil Apc and Vil Apc Huwe1hom mice culled at clinical endpoint. Note the huge numbers of tiny macroscopic adenomas visible in the Vil Apc Huwe1hom intestine (red arrows).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(c) H&E staining of intestinal cross sections from Vil Apc and Vil Apc Huwe1hom mice demonstrating the increased adenoma burden following Huwe1 deletion. Black arrows indicate individual adenomas. Scale bars = 200 µm.",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(d) Quantification of total tumour numbers per gut in sacrificed Vil Apc, Vil Apc Huwe1het and Vil Apc Huwe1hom mice. Deletion of Huwe1 led to a significant increase in the number of tumours per gut (Mann Whitney, n ≥ 5).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(a) H&E staining of control and Huwe1 deleted intestinal epithelium. Shortened villi in Huwe1 deficient tissue are indicated. Scale bars = 100 µm. (b) BrdU IHC of control and Huwe1 deleted intestinal epithelium. Scale bars = 100 µm. (c) PAS staining identifying Goblet cells. No gross changes were observed. Scale bars = 100 µm. (d) Lysozyme staining (Paneth cell marker) of control and Huwe1 deleted small intestine. Note the occurrence of lysozyme positive cells away from the crypt base (black arrows). Scale bars = 100 µm.",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(e) Dual Periodic acid-Schiff / Alcian blue staining to identify Paneth cell secretory vesicles (light blue / pink - marked with black arrows) and goblet cells (dark blue / purple - marked with red arrows). Note Paneth cell secretory vesicles are restricted to crypt base in both control and Huwe1 deficient small intestines (inset - black arrows). Scale bars = 100µm.",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(f) MMP7 staining of control and Huwe1 deleted small intestine. Note MMP7 staining is restricted to crypt base in Huwe1 deficient intestines. Scale bars = 100µm.",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(a) HUWE1 and MYC Western blot analysis of epithelial cell extractions from control and Huwe1 deficient intestines. Levels of MYC protein are significantly increased in normal intestines lacking HUWE1 (Mann Whitney, p = 0.04, n = 3).",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(b) QRT-PCR analysis of Myc expression in control and Huwe1 deficient intestines.",
    "ncbi_link": "Huwe1: 59026
Myc: 17869"
  },
  {
    "caption": "(c) MYC IHC in tumours from Vil Apc and Vil Apc Huwe1hom mice. Scale bars = 50 µm.",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(d) MYC Western blot in protein extracts from Vil Apc and Vil Apc Huwe1hom tumours. Levels of MYC protein are significantly increased in tumours lacking HUWE1 (Mann Whitney, p = 0.04, n = 3).",
    "ncbi_link": "Apc: 11789
HUWE1: 59026
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(e) QRT-PCR analysis of Myc expression in tumours from Vil Apc and Vil Apc Huwe1hom mice.",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Myc: 17869
Vil: 22349"
  },
  {
    "caption": "(a) Kaplan-Meier survival plot of cohorts of induced Vil Apc Pten, Vil Apc Pten Huwe1, Vil Apc Pten Myc and Vil Apc Pten Huwe1 Myc mice. Heterozygous deletion of Myc led to a specific and significant increase in survival of Huwe1 deleted animals (Vil Apc Pten Huwe1 vs Vil Apc Pten Huwe1 Myc, Log Rank, p < 0.001, n ≥ 16).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Myc: 17869
Pten: 19211
Vil: 22349"
  },
  {
    "caption": "(b) Quantification of total tumour numbers per gut in sacrificed Vil Apc Pten, Vil Apc Pten Huwe1, Vil Apc Pten Myc and Vil Apc Pten Huwe1 Myc mice. Heterozygous deletion of Myc did not reduce the number of tumours in Huwe1 deleted mice (Vil Apc Pten Huwe1 vs Vil Apc Pten Huwe1 Myc. Mann Whitney, n ≥ 10).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Myc: 17869
Pten: 19211
Vil: 22349"
  },
  {
    "caption": "(c) Kaplan-Meier survival plot of cohorts of induced AhCre-ERT Apc Pten and AhCre-ERT Apc Pten MycT58A mice. Overexpression of proteolytically stabilised MYC led to a significant reduction in survival (Log Rank, p < 0.001, n = 14 vs 21).",
    "ncbi_link": "Cre: 
Ah: 11622
Apc: 11789
ER: 13983///13982
Myc: 17869
Pten: 19211"
  },
  {
    "caption": "(d) Quantification of total tumour numbers per gut in sacrificed Apc Pten and Apc Pten MycT58A mice. Overexpression of proteolytically stabilised MYC did not increase the number of tumours in Apc Pten mice (Mann Whitney, n = 9 vs 19).",
    "ncbi_link": "Apc: 11789
MYC: 17869
Myc: 17869
Pten: 19211"
  },
  {
    "caption": "(a) H2AX Western blot in protein extracts from control and Huwe1 deficient intestinal epithelial cells. Band intensity relative to βactin displayed under each lane (Mann-Whitney, p = 0.04, n = 3 vs 3).",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(b) γ-H2AX IHC showing increased positivity in Huwe1 deleted intestinal cells. Scale bars = 50 µm.",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(c) γ-H2AX Western blot in protein extracts from control and Huwe1 deficient intestinal epithelial cells (Mann-Whitney, p = 0.04, n = 3 vs 3).",
    "ncbi_link": "Huwe1: 59026"
  },
  {
    "caption": "(d) γ-H2AX IHC of Vil Apc and Vil Apc Huwe1hom tumours, note increased positivity in Huwe1 deficient tumours. Scale bars = 50 µm.",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(a) Caspase 3 IHC of tumours from Lgr5 Apc and Lgr5 Apc Huwe1 mice either untreated or 6h post treatment with 7.5mg/kg cisplatin. Arrows identify caspase 3 positive cells. Scale bars = 50 µm. (b) Quantification of cisplatin treatment showing a significant increase in apoptosis in Huwe1 deficient tumour cells (Mann-Whitney, n = 3 vs 5).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Lgr5: 14160"
  },
  {
    "caption": "(c) Comparison of somatic mutation rate (mutations / Mb) between human tumours carrying HUWE1 mutations or not. Note the significant increase in mutational burden in HUWE1 mutated tumours (Mann-Whitney, p = 0.0002, n ≥ 15).",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "(d) Comparison of somatic mutation rate (mutations / Mb) between human tumours carrying HUWE1 mutations or not grouped according to MLH1 status. Note that the increased mutation rate is found primarily in tumours where MLH1 is not silenced indicating increased mutation rate (and HUWE1 mutation itself) is not due to silencing of MLH1 (Mann-Whitney, p = 0.0007, n ≥ 11).",
    "ncbi_link": "HUWE1: 10075
MLH1: 4292"
  },
  {
    "caption": "(e) Survival analysis of colorectal cancer patients treated with adjuvant chemotherapy divided by HUWE1 expression levels. Note the lowest HUWE1 expressing quartile of patients respond significantly better to chemotherapy. (f) Survival analysis of colorectal cancer patients not treated with adjuvant chemotherapy divided by HUWE1 expression levels. Note the lowest HUWE1 expressing quartile of patients do not survive significantly longer than those expressing higher levels of HUWE1 if not treated with chemotherapy.",
    "ncbi_link": "HUWE1: 10075"
  },
  {
    "caption": "(b) Kaplan-Meier survival plot of cohorts of induced Lgr5 Apc and Lgr5 Apc Huwe1 mice. Deletion of Huwe1 led to a significant reduction in survival of these animals (Log Rank, p < 0.001, n ≥ 15).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Lgr5: 14160"
  },
  {
    "caption": "(c) Lysozyme IHC demonstrating increased lysozyme positive cell numbers in tumours from Lgr5 Apc Huwe1 mice. Scale bars = 200 µm (low magnification), 100 µm (high magnification inset). (d) OLFM4 IHC demonstrating expanded stem cell population in Lgr5 Apc Huwe1 tumours. Scale bars = 200 µm (low magnification), 100 µm (high magnification inset).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Lgr5: 14160"
  },
  {
    "caption": "(a) MCL1 Western blot in protein extracts from Vil Apc and Vil Apc Huwe1hom tumours. Levels of MCL1 protein are significantly increased in tumours lacking HUWE1 (Mann Whitney, p = 0.04, n = 3).",
    "ncbi_link": "Apc: 11789
HUWE1: 59026
Huwe1: 59026
Vil: 22349"
  },
  {
    "caption": "(b) Kaplan-Meier survival plot of cohorts of induced Lgr5 Apc Huwe1 and Lgr5 Apc Huwe1 Mcl1 mice. Deletion of one copy of Mcl1 led to a significant increase in survival of these animals (Log Rank, p = 0.0052, n = 9 vs 10).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Lgr5: 14160
Mcl1: 17210"
  },
  {
    "caption": "(c) Ratio of adenoma / indolent lesions observed in Lgr5 Apc Huwe1 and Lgr5 Apc Huwe1 Mcl1het mice. Note the decreased ration of adenoma / indolent lesions observed upon Mcl1 deletion (Mann-Whitney, p=0.0281, n = 8 v 8).",
    "ncbi_link": "Apc: 11789
Huwe1: 59026
Lgr5: 14160
Mcl1: 17210"
  },
  {
    "caption": "E, Overlay of normalized (at 705 nm) difference spectra plus a difference spectrum of the photosensory domain in the presence of the bacterial HO BphO",
    "ncbi_link": "BphO: 879778"
  },
  {
    "caption": "(D) CMH2DCFDA staining of H2O2 and quantification of signal intensity in the muscle tissues of 50-day old control flies and flies with NDUFS2 or NDUFS3 knockdown (n=5 per group).",
    "ncbi_link": "NDUFS3: 38378
NDUFS2: 43798"
  },
  {
    "caption": "(A, B) Survival curves showing effect of neuronal dSirt2 knockdown on fly lifespan under normal and CPT-treatment conditions (n=3 groups, 20-25 flies per group). (C, D) Survival curves showing effect of muscle dFoxo knockdown on fly lifespan under normal and CPT-treatment conditions (n=3 groups, 20-25 flies per group). (E, F) Survival curves showing effect of neuronal ATG1 knockdown on fly lifespan under normal and CPT-treatment conditions (n=3 groups, 20-25 flies per group).",
    "ncbi_link": "ATG1: 39454
Foxo: 41709
Sirt2: 42414"
  },
  {
    "caption": "(A, B) Survival curves showing effect of CPT treatment on the lifespan of Mhc>APP.C99 flies (**p<0.01 logrank, **p<0.01 Wang Allison) (A) and elav>APP.BACE flies (**p<0.01 logrank, **p<0.01 Wang Allison) (B) (n=3 groups, 20-25 flies per group).",
    "ncbi_link": "APP: 351
BACE: 23621
elav: 31000
Mhc: 35007"
  },
  {
    "caption": "(E) Immunofluorescence images and data quantification showing effect of CPT on the formation of ubiquitin- and 6E10-positive amyloid aggregates in the brain of elav>APP.BACE flies (n=5).",
    "ncbi_link": "APP: 351
BACE: 23621
elav: 31000"
  },
  {
    "caption": "(G) Quantification of the effect of CPT on DA neuron number in the PPL1 cluster of elav>APP/BACE fly brain (n=4 sets, 5 brains per set).",
    "ncbi_link": "APP: 351
BACE: 23621
elav: 31000"
  },
  {
    "caption": "(a) Anti-VHR and anti-actin immunoblots of lysates of HeLa cells transfected with a control luciferase siRNA or VHR siRNA and cultured for the indicated number of days.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(b) Number of cells at the start of the experiment (200,000) and on day 3 for HeLa cells transfected with a control luciferase siRNA (black bars) or with VHR siRNA (white bars).",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(c) Light microscopy of HeLa cells transfected with a control luciferase siRNA or VHR siRNA and cultured for three days.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(d) Thymidine incorporation by HeLa cells transfected with a control luciferase siRNA or with VHR siRNA. The data represent the mean ± sd. (n = 3).",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(e) β-galactosidase staining of HeLa cells transfected with a control luciferase siRNA or VHR siRNA and cultured for three days. Note the increased number of blue-staining granules in many cells. (",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(f) Telomerase activity of cells treated with the indicated concentrations of VHR siRNA. Each sample was analysed in triplicate, with RNAse added to a fourth sample.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(a) Cell-cycle distribution and cell number count of cells transfected with control or VHR siRNA and observed for 4-5 days. The cells were stained with propidium iodide for DNA content and analysed by FACS after the indicated number of days in culture.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(b) Confocal microscopy of the same HeLa cells stained for VHR (green) and BrdU (red) to indicate S-phase entry, and DNA (DAPI, blue). Control siRNA-treated cells and cells treated with VHR are shown. The bottom panels represent merges of the 3 images above",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(e) Confocal microscopy of control or VHR siRNA-transfected HeLa cells stained for VHR (green) and phospho H3 (red) to indicate M-phase entry, and DNA (DAPI, blue). The bottom panels represent merges of the images above.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(f) Immunoblots of total lysates of control siRNA transfected cells and VHR siRNA cells with the indicated antibodies. Note that VHR was downregulated by approximately 80%, wheras actin levels were unchanged.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(g) Immunoblot with anti-p21Cip1-WAF1 of total lysates of cells transfected with control siRNA (lanes 1-2), two different VHR siRNAs cells (lanes 3-6) or another control siRNA (lanes 7-8). The scale bars represent 10 μm in b and e.",
    "ncbi_link": "VHR: 1845"
  },
  {
    "caption": "(a) Proliferation of cells transfected 3 days earlier with a combination of control siRNA or VHR siRNA together with Mek, Jnk or Mek plus Jnk siRNAs. The data are calculated as percentage of control (control siRNA alone) and represent the mean ± s.d. from three independent experiments. The starting cell numbers were 150,000 or 200,000 and the control cells had increased by 5.3, 5.0 and 13-fold in the three experiments.",
    "ncbi_link": "VHR: 1845
Mek: 5609
Jnk: 5599"
  },
  {
    "caption": "(F) Representative immunoblot of LC3 and p62 in MEFs of indicated genotype. MEFs were treated with tunicamycin (5 μg/ml) or vehicle control in the presence or absence of bafilomycin A1 (400 nM), and endogenous LC3 and p62 levels were measured by immunoblotting. Data represent the ratios of LC3-II to LC3-I and p62 to actin in the absence of bafilomycin, which were normalized LRRK+/+ MEFs. Error bars represent ±SD from four independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01.",
    "ncbi_link": "LRRK: 66725"
  },
  {
    "caption": "MEFs were transfected with mitochondrially targeted Cameleon. Free Ca2+ dynamics in the mitochondrial matrix were visualized using FRET. Mitochondrial [Ca2+] ([Ca2+]m) was continuously monitored by FRET imaging data are represented as absolute [Ca2+] in μmol. (C) Peak values of Ca2+ transients in MEFs transfected with IP3R or shRNA against IP3R, or treated with 2-AP (20 mM). Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "IP3R: 16438"
  },
  {
    "caption": "MEFs were transfected with mitochondrially targeted Cameleon. Free Ca2+ dynamics in the mitochondrial matrix were visualized using FRET. Mitochondrial [Ca2+] ([Ca2+]m) was continuously monitored by FRET imaging data are represented as absolute [Ca2+] in μmol. (D) Peak values of Ca2+ transients in MEFs transfected with VDAC1 or shRNA against VDAC1. Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "VDAC1: 22333"
  },
  {
    "caption": "(F) In situ PLA images using anti-IP3R and anti-VDAC1 antibodies. Scale bar: 20 μm. Data represent fluorescent in MEFs normalized LRRK2+/+ MEFs. Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(G) Peak values of Ca2+ transients in MEFs transfected with synthetic tethering protein (TOM-mRFP-ER) to induce artificial tethering of the ER and mitochondria. Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "mRFP: 
TOM: 28185"
  },
  {
    "caption": "(C) Peak values of Ca2+ transients in MEFs transfected with deletion constructs of LRRK2(G2019S). Error bars represent ±SD from six independent experiments. Data information: For graph , the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(D) Binding assays to detect interactions between deletion constructs of LRRK2(G2019S) and E3 ubiquitin ligases. HEK293 cells were transfected with deletion constructs of LRRK2(G2019S) and E3 ubiquitin ligases, and cell lysates were immunoprecipitated with antibody against the V5 or HA epitope. Precipitated proteins were subjected to SDS/PAGE, and blots were stained with antibody against the V5 or HA epitope, as indicated the right of each panel.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "Peak values of Ca2+ transients in MEFs transfected with ligase-active MARCH5(WT), MULAN(WT), and Parkin(W403A) [Parkin(WA)] or dominant-negative forms of MARCH5(H43W) [MARCH(HW)], MULAN(C339A) [MULAN(CA)], Parkin(C431A) [Parkin(CA)] (E) Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05",
    "ncbi_link": "MARCH: 69104
MARCH5: 69104
MULAN: 68350
Parkin: 50873"
  },
  {
    "caption": "Peak values of Ca2+ transients in MEFs transfected with active USP30 or inactive USP30(C77S) [USP(CS)] (F). Error bars represent ±SD from six independent experiments. Data information: For graph the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05",
    "ncbi_link": "USP: 100756
USP30: 100756"
  },
  {
    "caption": "(A) Immunoprecipitation/Immunoblot of phosphorylated E3 ubiquitin ligases in LRRK2+/+ and LRRK2(G2019S)-expressing MEFs treated with vehicle (Control) or tunicamycin (1 μg/ml). Endogenous PERK, MARCH5, MULAN and Parkin were immunoprecipitated with antibody, and precipitates were immunoblotted with antibody indicated at the right. Data represent the ratio of phosphorylated to total protein levels. Error bars represent ±SD from independent experiments. Data information: For graph A the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(B) Immunoprecipitation/immunoblot of phosphorylated E3 ubiquitin ligases and mitofusin 2 in MEFs in the of tunicamycin (5 μg/ml). LRRK2(G2019S) MEFs were also pretreated with LRRK2-IN-1 (1 μM). MEFs were transfected with each E3 ubiquitin ligase and biquitin and lysates were immunoprecipitated with antibody against the Myc or HA epitope. Precipitated proteins were subjected to SDS/PAGE, and blots were stained with antibody against the Myc epitope, phosphoserine or mitofin2 as indicated to the right of each panel. Mfn2: mitofusin 2, Ub: ubiquitin. Data represent ratios of phosphorylated to total E3 ubiquitin ligase and mitofusin2 to actin. Error bars represent ±SD from four independent experiments. Data information: For graph B, the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(E) Immunoprecipitation/Immunoblot of phosphorylated E3 ubiquitin ligases and mitofusin 2 in LRRK2(G2019S)-expressing MEFs transfected with the increasing amounts of LRRK2-d1-V5 (1, 5, 25 μg/106 cells) treated with tunicamycin (1 μg/ml). Endogenous MARCH5, MULAN and Parkin were immunoprecipitated with antibody, and precipitates were immunoblotted with antibody indicated at the right. Endogenous mitofusin 2 was immunoblotted with anti-mitofusin 2 antibody. Data represent the ratio of phosphorylated to total protein levels of MARCH5, MULAN and Parkin, and the ratio of mitofusin 2 to actin. Error bars represent ±SD from independent experiments. Data information: For graph E, the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05, **P < 0.01",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(A) Immunoprecipitation/mmunoblot of E3 ubiquitin ligases by PERK and the binding to mutant LRRK2. HEK293 cells were transfected with PERK and either MARCH5, MULAN or Parkin, LRRK2, LRRK2(D1994A) or LRRK2(S1292D). Cell lysates were immunoprecipitated with antibody against Myc or V5, and precipitates were immunoblotted with antibody indicated the right.",
    "ncbi_link": "PERK: 13666
LRRK2: 66725
MARCH5: 69104
MULAN: 68350
Parkin: 50873"
  },
  {
    "caption": "(C) Binding assays to detect interactions between phosphomimetic LRRK2(S1292D) or phosphorylation-defective LRRK2(S1292A) and E3 ubiquitin ligases. HEK293 cells were transfected with LRRK2 mutants and E3 ubiquitin ligases lysates were immunoprecipitated with antibody against Myc or V5 epitope. Precipitated proteins were subjected to SDS/PAGE, for immunoblotwith antibody against V5 or Myc.",
    "ncbi_link": "LRRK2: 66725"
  },
  {
    "caption": "(D) Immunoprecipitation/mmunoblot of E3 ubiquitin ligases by PERK-ΔN in the presence of LRRK2(S1292A) or LRRK2(S1292D). HEK293 cells were transfected with MARCH5, MULAN, Parkin, and PERK-ΔN LRRK2(S1292A) or LRRK2(S1292D). Cell lysates were immunoprecipitated with antibody against Myc, and precipitates were immunoblotted with antibody indicated the right.",
    "ncbi_link": "PERK: 13666
LRRK2: 66725
MARCH5: 69104
MULAN: 68350
Parkin: 50873"
  },
  {
    "caption": "(A) Immunoblot of LC3 and p62. MEFs were transfected with PERK-ΔN or PERK shRNA. Endogenous LC3 and p62 levels were measured by immunoblotting. Data represent the ratios of LC3-II to LC3-I and p62 to actin normalized LRRK+/+ MEFs. Error bars represent ±SD from four independent experiments. Data information: For graph A, the P values was determined by a Mann-Whitney U test. ns = not significant, *P < 0.05.",
    "ncbi_link": "PERK: 13666
LRRK: 66725"
  },
  {
    "caption": "(B) Peak values of Ca2+ transients in MEFs transfected with PERK-ΔN or PERK shRNA. Error bars represent ±SD from six independent experiments.",
    "ncbi_link": "PERK: 13666"
  },
  {
    "caption": "A The diameter (d) of the fluorescence signaling of H2B tagged with photo-activatable GFP (PAGFP-H2B) is used to quantify chromatin expansion across 120 seconds after induction of DNA damage using intercalating DNA dye and local irradiation with a laser.",
    "ncbi_link": "PAGFP: 
H2B: 8344///255626///8347///440689///8349"
  },
  {
    "caption": "C Quantified chromatin expansion in cells not transfected (control) and cells transfected with each mCherry-tagged histone (as indicated). Data is represented as in B (n > 30 cells, 3 bio. repl.; *, p < 0.05 compared to mCherry-H2A-expressing cells using unpaired, two-tailed Student's T-test).",
    "ncbi_link": "mCherry: 
H2A: 55506"
  },
  {
    "caption": "D Chromatin expansion in Hela cells containing a doxocyclin (doxo.)-inducible macroH2A1.1 transgene. Chromatin expansion assay was performed 48 hours after induction and expression was controlled by anti-macroH2A1.1-immunoblotting. Data is represented as in B (n > 30 cells, 3 bio. repl.; *, p < 0.05 using unpaired, two-tailed Student's T-test).",
    "ncbi_link": "macroH2A1.1: 9555"
  },
  {
    "caption": "Quantified chromatin expansion in cells transfected with indicated histone constructs. Boxplots represent single cell measurement of chromatin expansion at 120 sec. post DNA damage (n > 30 cells, 3 bio. repl.). The box limits correspond to 25th and 75th percentiles, the bold line indicates median and cross indicates the average values. (*, p<0.05 using unpaired two-tailed Student's T-test comparing to H2A; n.s., not significant).",
    "ncbi_link": "H2A: "
  },
  {
    "caption": "Quantified chromatin expansion in cells transfected with indicated histone constructs. Boxplots represent single cell measurement of chromatin expansion at 120 sec. post DNA damage (n > 30 cells, 3 bio. repl.). The box limits correspond to 25th and 75th percentiles, the bold line indicates median and cross indicates the average values. (*, p<0.05 using unpaired two-tailed Student's T-test comparing to H2A; n.s., not significant).",
    "ncbi_link": "H2A: "
  },
  {
    "caption": "A Western blot showing the expression of macroH2A proteins in control HepG2 cells, knock-down for macroH2A1 and macroH2A2 (DKD) and DKD with ectopic expression of the indicated YFP-tagged constructs. H3 is used as a loading control.",
    "ncbi_link": "YFP: 
macroH2A1: 9555
macroH2A2: 55506"
  },
  {
    "caption": "Representative ISH image (light field) showing TNF expression at the murine fracture site at 24 h after fracture. Scale bar, 250 μm. Red box indicates region of interest.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intravenously infected with VSV-GFP (2 × 108 PFU/mouse), and serum samples were collected at 12 hpi (hours post-infection). (A) Virus titer was analyzed in a plaque assay.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intravenously infected with VSV-GFP (2 × 108 PFU/mouse), and serum samples were collected at 12 hpi (hours post-infection). (B) Secretion of IFN-β, IL-6, IL-12, and TNFα was measured in specific ELISAs.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "C MARCH2+/+ (n = 6) or MARCH2-/- (n = 6) mice were intravenously injected with poly(I:C) (200 μg/mouse). Serum samples were collected at 2 hpi and secretion of IFN-β, IL-6, IL-12, and TNFα was measured in specific ELISAs.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intraperitoneally challenged with 1 × 106 CFU of Listeria monocytogenes. (D) The percentage of surviving mice (D, log-rank test, **P < 0.01)",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intraperitoneally challenged with 1 × 106 CFU of Listeria monocytogenes. body weight changes for each group (E) are shown.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intraperitoneally challenged with 1 × 106 CFU of Listeria monocytogenes. (F, G) At 3 dpc, the bacterial load in the spleen (F) and liver (G) was examined.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were intraperitoneally challenged with 1 × 106 CFU of Listeria monocytogenes. (H-J) Amount of IL-6, IL-12, CCL5, and CXCL10 in serum (H), spleen (I), and liver (J) of mice in each group at 24 hpc.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were challenged intraperitoneally with LPS (24 mg/kg). Percentage of surviving mice (A, log-rank test, **P < 0.01)",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "MARCH2+/+ (n = 8) or MARCH2-/- (n = 8) mice were challenged intraperitoneally with LPS (24 mg/kg). body weight changes (B) in each groups.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "C MARCH2+/+ (n = 4) or MARCH2-/- (n = 4) mice were challenged intraperitoneally with LPS (24 mg/kg). Representing slides of H&E staining of spleen sections from each group. Scale bar, 6mm.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "D MARCH2+/+ (n = 6) or MARCH2-/- (n = 6) mice were challenged intraperitoneally with LPS (24 mg/kg). Levels of IL-6, TNF-α, CXCL-10, CCL-5 in serum from mice in each groups were measured at12 hpc by ELISA.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "E, F MARCH2+/+ (n = 5) or MARCH2-/- (n = 5) mice were challenged intraperitoneally with LPS (24 mg/kg). cDNA was prepared from total RNA extracted from spleen and liver of mice. Expression of mRNA encoding IL-6, TNF-α, CXCL10, IL-1β in spleen (E) and liver (F) from mice in each group was examined at 6 hpc by qPCR.",
    "ncbi_link": "CXCL10: 15945
IL-1β: 16176
IL-6: 16193
MARCH2: 224703
TNF-α: 21926"
  },
  {
    "caption": "A-C BMDMs isolated from MARCH2+/+ or MARCH2-/- mice were infected with PR8-GFP (A, MOI=3), VSV-GFP (B, MOI = 5), or HSV-GFP (C, MOI = 3), and virus titer was measured in a plaque assay.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "D, E BMDMs isolated from MARCH2+/+ or MARCH2-/- mice were infected with viruses or treated with poly(I:C) (80 µg/ml) or poly (dA:dT) (1 µg/ml). The concentration of secreted IFN-β (D) and IL-6 (E) in the supernatants was measured in an ELISA.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "PBMCs isolated from whole peripheral blood from MARCH2+/+ or MARCH2-/- mice were infected with VSV-GFP (MOI =1). (F) The virus titer was measured in a plaque assay.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "PBMCs isolated from whole peripheral blood from MARCH2+/+ or MARCH2-/- mice were infected with VSV-GFP (MOI =1). (G) Concentration of IFN-β and IL-6 in the supernatant was measured in an ELISA.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "PMs isolated from MARCH2+/+ or MARCH2-/- mice infected with CVB-GFP (MOI = 3). (H) Virus titer was measured in a plaque assay.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "PMs isolated from MARCH2+/+ or MARCH2-/- mice infected with CVB-GFP (MOI = 3). (I) Concentration of IFN-β and IL-6 in the supernatant was measured in an ELISA.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "J, K BMDMs (J) or PMs (K) isolated from MARCH2+/+ or MARCH2-/- mice were infected with Salmonella typhimurium or L. monocytogenes, or treated with LPS or zymosan. The concentration of IL-6 and IL-12 in supernatant was analyzed in an ELISA.",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "L, M RAW 264.7 cells transfected with control siRNA (si-control) or MARCH2-specific siRNA (si-MARCH2) were infected with PR8-GFP (MOI = 1), VSV-GFP (MOI = 0.5), poly (I:C) (20 µg/ml) or HSV-GFP (MOI = 1) poly (dA:dT) (1 µg/ml) and IFN-β (L), and IL-6 (M) levels in the supernatant were measured in an ELISA.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "N RAW 264.7 cells transfected with control siRNA (si-control) or MARCH2-specific siRNA (si-MARCH2) were infected with S. typhimurium, or L. monocytogenes, or treated with LPS (100 ng/ml) or zymosan (100 µg/ml) and IL-6 secretion into the cell supernatant was measured in an ELISA",
    "ncbi_link": "MARCH2: 224703"
  },
  {
    "caption": "HEK293T cells were transfected with a firefly luciferase reporter plasmid encoding the IFN-β promoter , plus a TK renilla plasmid and an increasing dose of flag-tagged MARCH2 plasmid (50, 100, 200, 400 ng) plus expression plasmids for RIG-I 2CARD, RIG-I, MDA-5, MAVS or stimulated with poly (I:C), for 24 h. Results are expressed relative to those of renilla luciferase alone (Internal control).",
    "ncbi_link": "flag: 
luciferase: 
TK: 
RIG-I: 23586
MDA-5: 64135
IFN-β: 3456
MARCH2: 51257
MAVS: 57506"
  },
  {
    "caption": "HEK293T cells were transfected with a firefly luciferase reporter plasmid encoding the IFN-β promoter plus a TK renilla plasmid and an increasing dose of flag-tagged MARCH2 plasmid (50, 100, 200, 400 ng) plus expression plasmids for TBK1 TRIF , for 24 h. Results are expressed relative to those of renilla luciferase alone (Internal control).",
    "ncbi_link": "flag: 
luciferase: 
TK: 
IFN-β: 3456
MARCH2: 51257
TBK1: 29110
TRIF: 353376"
  },
  {
    "caption": "HEK293T cells were transfected with a firefly luciferase reporter plasmid encoding the the NF-κB promoter plus a TK renilla plasmid and an increasing dose of flag-tagged MARCH2 plasmid (50, 100, 200, 400 ng) plus expression plasmids for TRAF 6, TRAF 2, NEMO for 24 h. Results are expressed relative to those of renilla luciferase alone (Internal control).",
    "ncbi_link": "flag: 
luciferase: 
TK: 
NEMO: 8517
MARCH2: 51257
TRAF 2: 7186
TRAF 6: 7189"
  },
  {
    "caption": "HEK293T cells were transfected with a firefly luciferase reporter plasmid encoding the NF-κB promoter plus a TK renilla plasmid and an increasing dose of flag-tagged MARCH2 plasmid (50, 100, 200, 400 ng) plus expression plasmids for TBK1 TRIF , for 24 h. Results are expressed relative to those of renilla luciferase alone (Internal control).",
    "ncbi_link": "flag: 
luciferase: 
TK: 
MARCH2: 51257
TBK1: 29110
TRIF: 353376"
  },
  {
    "caption": "Interaction between MARCH2 and NEMO in response to viral infection. HEK293T cells (E) were infected with NDV-GFP in a time-dependent manner in the presence of MG132 (proteasome inhibitor, 10 μM). Cell lysates were subjected to immunoprecipitation with an anti-NEMO antibody, followed by immunoblotting with an anti-MARCH2 antibody.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Interaction between MARCH2 and NEMO in response to viral infection. Raw264.7 cells (F) were infected with NDV-GFP in a time-dependent manner in the presence of MG132 (proteasome inhibitor, 10 μM). Cell lysates were subjected to immunoprecipitation with an anti-NEMO antibody, followed by immunoblotting with an anti-MARCH2 antibody.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "J Confocal microscopy was conducted to examine time-dependent colocalization of MARCH2 and NEMO in HeLa cells expressing TLR2 upon zymosan treatment (100 μg/ml) in the presence of MG132 (10 μM). Arrow indicates the co-localized NEMO and MARCH2 protein.",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": "NEMO degradation assay. (A) HEK293T cells were transfected with different doses of Strep-tagged MARCH2 in the presence HA-tagged NEMO plasmid.",
    "ncbi_link": "HA: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "NEMO degradation assay. (B) MARCH2+/+ and MARCH2-/- HEK293T cells were infected with PR8-GFP (MOI=1) in time-dependent manner. Cells were harvested following infection, NEMO expression level, total and phosphorylated IRF-3, and TBK-1 were measured by immunoblotting. β-actin was used to confirm equal loading of protein.",
    "ncbi_link": "GFP: 
MARCH2: 224703"
  },
  {
    "caption": "C HEK293T cells transfected with a Strep-tagged empty vector or MARCH2 together with GST-tagged NEMO were treated with MG132 (10 μM), chloroquine, NH4Cl, or Z-VAD for 6 h before harvest. Whole cell lysates were subjected to immunoblotting with indicated antibodies.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "D HEK293T cells were transfected with different doses of Strep-tagged MARCH2 together with and GST-tagged NEMO plasmid. MG132 (10 μM) was added to cells for 6 h prior to harvest. Whole cell lysates were subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "F HEK293T cells transfected with Strep-tagged empty vector or MARCH2 with GST-tagged NEMO and each different HA-tagged ubiquitin mutants (indicated lysine (K) only, other lysines (K) mutated to arginines (R) were treated with MG132 (10 μM) for 6 h before harvest. Lysates were subjected to pull down with GST beads, followed by immunoblotting with an anti-HA antibody. Whole cell lysates were determined by immunoblotting with the indicated antibodies.",
    "ncbi_link": "GST: 
HA: 
NEMO: 8517
MARCH2: 51257
ubiquitin: 7316"
  },
  {
    "caption": "G NEMO ubiquitination assay. HEK293T cells were transfected with different doses of Strep-tagged MARCH2 in the presence of a HA-tagged NEMO plasmid. Lysates were immunoprecipitated with anti-HA antibody followed by immunoblotting with anti-K48 antibody.",
    "ncbi_link": "HA: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "MARCH2+/+ HEK293T cells harboring empty vector or MARCH2-/- HEK293T cells harboring empty vector, Flag-tagged MARCH2, or MARCH2CCH (a mutant harboring mutations in residues within the catalytic domain: C64S, C67S, and H90Q) were infected with VSV-GFP (MOI = 0.05). Viral replication was assessed under a fluorescence microscope (H)",
    "ncbi_link": "Flag: 
GFP: 
MARCH2: 51257"
  },
  {
    "caption": "MARCH2+/+ HEK293T cells harboring empty vector or MARCH2-/- HEK293T cells harboring empty vector, Flag-tagged MARCH2, or MARCH2CCH (a mutant harboring mutations in residues within the catalytic domain: C64S, C67S, and H90Q) were infected with VSV-GFP (MOI = 0.05). by measuring GFP expression using a fluorescence modulator",
    "ncbi_link": "Flag: 
GFP: 
MARCH2: 51257"
  },
  {
    "caption": "MARCH2+/+ HEK293T cells harboring empty vector or MARCH2-/- HEK293T cells harboring empty vector, Flag-tagged MARCH2, or MARCH2CCH (a mutant harboring mutations in residues within the catalytic domain: C64S, C67S, and H90Q) were infected with VSV-GFP (MOI = 0.05). (J) Levels of IFN-β (top) and IL-6 (bottom) in cell supernatants were measured in an ELISA.",
    "ncbi_link": "Flag: 
GFP: 
MARCH2: 51257"
  },
  {
    "caption": "K In vitro ubiquitination assay for NEMO. HEK293T cells were transfected with GST-tagged NEMO, Strep-tagged MARCH2 or MARCH2CCH individually. Immunoprecipitates were incubated with a reaction mixture containing ubiquitin, E1, and UbcH6 (E2), followed by immunoblotting with an anti-K48-linkage specific polyubiquitin antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "(B) HEK293T cells were transfected with Strep-tagged MARCH2 domain constructs together with GST-tagged NEMO. Whole cell lysates were subjected to a Strep-PD assay, followed by immunoblotting with an anti-GST antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "(D) HEK293T cells were transfected with GST-tagged NEMO domain constructs together with Strep-tagged MARCH2-TM. Whole cell lysates were subjected to a Strep-PD assay, followed by immunoblotting with an anti-GST antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "(F) HEK293T cells were transfected with HA-tagged NEMO domain constructs together with GST-tagged MARCH2. Whole cell lysates were subjected to a GST-PD assay, followed by immunoblotting with an anti-HA antibody.",
    "ncbi_link": "GST: 
HA: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "G HEK293T cells transfected with His-tagged ubiquitin and HA-tagged NEMO WT or NEMO lacking the CC1 domain together with Strep-tagged empty vector or MARCH2 were treated with MG132 (10 μM) for 6 h before harvest. Lysates were subjected to immunoprecipitation with an anti-HA antibody, followed by immunoblotting with an anti-His antibody. WCL were subjected to immunoblotting with anti-HA, anti-Strep, or anti-β-actin antibody.",
    "ncbi_link": "HA: 
His: 
NEMO: 8517
MARCH2: 51257
ubiquitin: 7316"
  },
  {
    "caption": "(I) HEK293T cells transfected with GST-tagged NEMO mutants together with Strep-tagged empty vector or MARCH2 were subjected to immunoblotting with anti-GST, anti-Strep, or anti-β-actin antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "J HEK293T cells transfected with HA-tagged ubiquitin and GST-tagged NEMO mutants together with Strep-tagged empty vector or MARCH2 were subjected to pulldown with GST beads, followed by immunoblotting with anti-Lys48 (K48)-linkage specific polyubiquitin (K48-ub), anti-Lys63 (K63)-linkage specific polyubiquitin (K63-ub), or anti-Strep antibody. Whole cell lysates were determined by immunoblotting with the indicated antibodies.",
    "ncbi_link": "GST: 
HA: 
NEMO: 8517
MARCH2: 51257
ubiquitin: 7316"
  },
  {
    "caption": "A HEK293T cells were transfected with GST-tagged NEMO-WT and its point mutants with or without Strep-tagged MARCH2. Whole cell lysates were subjected to immunoblotting with the indicated antibodies.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "B HEK293T cells were transfected with GST-tagged NEMO-WT and its point mutants together with Strep-tagged MARCH2 in the presence of MG132. Whole cell lysates were subjected to a GST-PD assay, followed by immunoblotting with an anti-K48 linkage specific polyubiquitin antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "C In vitro ubiquitination assay for NEMO-K326R. HEK293T cells were transfected with GST-tagged NEMO, GST-tagged NEMO-K326R or Strep-tagged MARCH2 individually. Immunoprecipitates were incubated with a reaction mixture containing ubiquitin, E1, and UbcH6 (E2), followed by immunoblotting with an anti-K48-linkage specific polyubiquitin antibody.",
    "ncbi_link": "GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "HEK293T cells transfected with GST-tagged empty vector, NEMO-WT, or NEMO-K326R, with or without Strep-tagged MARCH2 were infected with VSV-GFP. (D-F) Viral replication was determined by fluorescence microscopy (D)",
    "ncbi_link": "GFP.: 
GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "HEK293T cells transfected with GST-tagged empty vector, NEMO-WT, or NEMO-K326R, with or without Strep-tagged MARCH2 were infected with VSV-GFP. , fluorescence absorbance (E)",
    "ncbi_link": "GFP.: 
GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "HEK293T cells transfected with GST-tagged empty vector, NEMO-WT, or NEMO-K326R, with or without Strep-tagged MARCH2 were infected with VSV-GFP. plaque assay (F).",
    "ncbi_link": "GFP.: 
GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "HEK293T cells transfected with GST-tagged empty vector, NEMO-WT, or NEMO-K326R, with or without Strep-tagged MARCH2 were infected with VSV-GFP. (G) IFN-β and IL-6 in the cell supernatants were measured in an ELISA.",
    "ncbi_link": "GFP: 
GST: 
NEMO: 8517
MARCH2: 51257"
  },
  {
    "caption": "H, I IFN-β (H) and NF-κB (I) luciferase reporter assay.",
    "ncbi_link": "IFN-β: 3456"
  },
  {
    "caption": "Six representative images of MT networks extracted from MT STORM images of HRPE cells under combinative KDs. Cells were rotated to orient their leading edges locating in the 1st quadrant. Upper: control cell; CLASPs KD cell; GCC185 KD cell. Lower: CLASPs + GCC185 KD cell; CAMSAP2 KD cell; AKAP450 KD cell. Red: GaMT; Green: non-GaMT. Scale bar: 5 μm. Box-whisker plot presents the ratio of GaMT/non-GaMT under combinative KDs. (1 representative of 3 independent experiments and n= 12 cells). The ends of the whiskers are set at 10% and 90% of the entire population. *p < 0.05, **p < 0.01, ***p < 0.001, ns, no significant difference, unpaired t-test.",
    "ncbi_link": "AKAP450: 10142
CAMSAP2: 23271
CLASPs: 23122///23332
GCC185: 9648"
  },
  {
    "caption": "Five representative images of MT repair sites in HRPE cells under combinative KDs. Cells were rotated to orient their leading edges locating in the 1st quadrant. From left to right, control cell, CLASPs&GCC185 KD cell, CAMSAP2 KD cell, AKAP450 KD cell and Centrinone-B treated cell. Grey: α-tubulin; red: GTP-tubulin. Scale bar: 20 μm. Box-whisker plot presents intensity analysis of MT repair sites in HRPE cells under combinative KDs. (1 representative of 3 independent experiments and n= 20 cells). ***p < 0.001, unpaired t-test.",
    "ncbi_link": "AKAP450: 10142
CAMSAP2: 23271
CLASPs: 23122///23332
GCC185: 9648"
  },
  {
    "caption": "Random migration of HRPE cells during 24 h. Upper: control cell; Middle: CAMSAP2 KD cell; Lower: CLASPs&GCC185 KD cell. Red arrow and white dashed lines indicate the migration direction. Different migration trajectories are distinguished with different colors. Scale bar: 50 μm. Rose-plot presents the representative directionality of an HRPE cell. (B) control cell; (C) CAMSAP2 KD cell; (D) CLASPs&GCC185 KD cell. Box-whisker plot presents the migration persistence of control cell, CAMSAP2 KD cell and CLASPs&GCC185 KD cell. (1 representative of 3 independent experiments and n= 34 cells). The ends of the whiskers are set at 10% and 90% of the entire population, ***p < 0.001, unpaired t-test.",
    "ncbi_link": "CAMSAP2: 23271
CLASPs: 23122///23332
GCC185: 9648"
  },
  {
    "caption": "Angle change curve of cell, nucleus and Golgi. Red-dashed line: laser angle; Blue line: nucleus angle; Orange line: cell angle; Green line: Golgi angle. H: control cell; I: CAMSAP2 KD cell; J: CLASPs&GCC185 KD cell. Box-whisker plot shows the total time required for the nucleus, Golgi and cell body reaching the given laser angle. Blue: time required for nucleus; Green: time required for Golgi; Orange: time required for cell body. (1 representative of 3 independent experiments and n= 14 cells). The ends of the whiskers are set at 10% and 90% of the entire population, ***p < 0.001, ns, no significant difference, unpaired t-test.",
    "ncbi_link": "CAMSAP2: 23271
CLASPs: 23332///23122
GCC185: 9648"
  },
  {
    "caption": "Examples of cargo delivery towards the leading edge, time series present at 40 s, 80 s and 120 s, respectively. B: control cell; C: CAMSAP2 KD cell; D: CLASPs&GCC185 KD cell. Red arrow heads indicate cargo current position. Size of cropped regions: 30 μm x 5 μm.",
    "ncbi_link": "CAMSAP2: 23271
CLASPs: 23122///23332
GCC185: 9648"
  },
  {
    "caption": "(A) Relative expression of the BBSome subunits in the indicated organs and T cells measured by qPCR. CT values of the BBS genes were normalized to the geometric mean of the CT values of reference genes Gapdh, Tubb2a, and Eef1a1. The expression levels are normalized to those of brain (=1). Mean+SD. Three biological replicates (the result of each biological replicate is a median of three technical replicates).",
    "ncbi_link": "Eef1a1: 13627
Gapdh: 14433
Tubb2a: 22151"
  },
  {
    "caption": "(D) Immunoblot analysis of BBS4 expression in testes and thymi lysates of Bbs4+/+ (WT), Bbs4GT/+, and Bbs4GT/GT mice. β-actin staining serves as a loading control. A representative experiment out of three biological replicates in total is shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(E) Immunoblot analysis of BBS4 expression in the brain lysates of Bbs4+/+, Bbs4GT/GT, and Bbs4KO/KO mice. β-actin staining served as a loading control. A representative experiment out of two biological replicates is shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(F) Hematoxylin and eosin staining of sections of seminiferous tubules from ~4 weeks old Bbs4+/+ (n=2 mice) and Bbs4GT/GT (n=4) males. Scale bar, 100 µm. Representative images are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(G) Genotypic ratio of Bbs4+/+, Bbs4GT/+ or Bbs4KO/+ (Het), and Bbs4GT/GT (GT) or Bbs4KO/KO (KO) offspring at weaning from mating of Bbs4GT/+ (n=145 pups) or Bbs4+/KO (n=168 pups) parents. Binomial test was used for statistical comparison of the observed distribution to the expected Mendelian ratio.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(H) Bbs4+/+ and Bbs4GT/GT female littermates at 20 weeks of age. Representative litter out of seven in total. (I) Bbs4+/+ and Bbs4KO/KO female littermates at 20 weeks of age. Representative litter out of five in total. ",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(J) Growth curves of Bbs4-deficient mice, mean ± SD is shown. Females: Bbs4+/+ (n=12 mice), Bbs4GT/GT (n=12), Bbs4KO/KO (n=6). Males: Bbs4+/+ (n=6 mice), Bbs4GT/GT (n=7), Bbs4KO/KO (n=5).",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(K) Leptin concentration in blood plasma taken from young adult (7-8 weeks) or mid-age (14-20 weeks) mice. Young adult mice: Bbs4+/+ (n=4 mice), Bbs4KO/KO (n=3), analyzed in two independent experiments. Mean+SEM. Mid-age adult mice: Bbs4+/+ (n=7 mice), Bbs4KO/KO (n=5), Bbs4GT/GT (n=3), analyzed in 4 independent experiments. Kruskal-Wallis tests was used for the statistical analysis. Mean+SEM.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the bone marrow (BM) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (A) Percentage of B220low positive cells in the bone marrow . Up: Bbs4+/+ n=9, Bbs4GT/GT n=10. Down: Bbs4+/+ (n =11), Bbs4KO/KO (n=10). Statistical significance was calculated using two-tailed Mann-Whitney test. Medians are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the bone marrow (BM) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (B) Percentage of B-cell precursors (IgM- IgD-) in the bone marrow. Gated on viable B220+ cells. Up: Bbs4+/+ (n=9), Bbs4GT/GT (n=10). Down: Bbs4+/+ (n =11), Bbs4KO/KO (n=10). Statistical significance was calculated using two-tailed Mann-Whitney test. Medians are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the bone marrow (BM) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (C) Percentage of pre-B cells (CD43- CD24high) in the bone marrow of Bbs4+/+ (n=11) and Bbs4KO/KO mice (n=10). Gated on viable B220+ IgM- IgD- cells. Statistical significance was calculated using two-tailed Mann-Whitney test. Medians are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the spleens (SPL) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (D) Percentage of late mature (IgM- IgD+) B cells in the spleen of Bbs4+/+ (n=11) and Bbs4KO/KO mice (n=10) Gated on viable CD19+ cells. Statistical significance was calculated using two-tailed Mann-Whitney test. Medians are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the spleens (SPL) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (E) An alternative analysis of the experiment shown in (D). Geometric mean fluorescence intensity (MFI) of BV421 (IgM) on IgD+ B cells was determined. Mean of MFI values for each genotype per experiment was quantified, and obtained values were normalized to Bbs4+/+ (=1) for each experiment. Two-tailed One Sample Wilcoxon Signed Rank Test was used for the statistical analysis.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from the spleens (SPL) of 18-25 weeks old Bbs4+/+ (WT), Bbs4GT/GT, and Bbs4KO/KO mice were analyzed by flow cytometry. Number of analyzed mice (n) is indicated. Six (Bbs4GT/GT strain and Bbs4WT/WT controls) or eight (Bbs4KO/KO strain and Bbs4WT/WT controls) independent experiments were performed. (F) Percentage of splenic marginal zone (MZ) B cells (CD23- CD1d+) in Bbs4+/+ controls (n=10) and Bbs4KO/KO mice (n=9) was determined. Gated on viable CD19+, IgD- IgM+, CD138- cells. Statistical significance was calculated using two-tailed Mann-Whitney test. Medians are shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(A,B) Splenocytes isolated from Bbs4+/+ (n=4 mice) and Bbs4GT/GT (n=3) B-cell transgenic B1-8 littermates were activated with 4-hydroxy-3-nitrophenylacetic acid succinimide ester-loaded T2-Kb cells in three independent experiments. Percentage of activated B cells (gated as CD69+ B220+ IgLλ+ viable cells) in the samples without T2-Kb (negative control), and in the samples with T2-Kb added in ratios 1:10 or 1:3 was determined by flow cytometry. (A) Representative mice are shown. (B) Mean±SEM. Statistical significance was calculated using two-tailed Mann-Whitney test.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(C) B cells from 18-20 weeks old Bbs4KO/KO (red circle, n=3 mice), and control mice (Bbs4+/+, dark grey square, n=4, or Bbs4+/KO, light grey square, n=2) were activated with F(ab')2-goat anti-mouse IgM (Mu chain). Percentage of activated B cells (gated as CD69+ CD19+ viable cells) was determined by flow cytometry. Representative experiment out of three biological replicates is shown. Mean±SEM. Statistical significance was calculated using two-tailed Mann-Whitney test.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "(D) CFSE-loaded T cells isolated from lymph nodes of Bbs4FL/FL OT-I Rag2KO/KO (OT-I) and CD4-Cre Bbs4FL/FL OT-I Rag2KO/KO (Bbs4 cKO, OT-I) littermates were incubated with DDAO-labeled WT splenocytes loaded with OVA peptide or with the indicated altered peptide ligands for 20 min. Percentage of T cells conjugated with the APCs was determined by flow cytometry. Four biological replicates were performed. Mean+SEM. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all peptides.",
    "ncbi_link": "Bbs4: 102774
CD4: 12504
Cre: 2777477
Rag2: 19374"
  },
  {
    "caption": "500 or 1000 T cells isolated from lymph nodes of Bbs4FL/FL OT-I Rag2KO/KO (OT-I) and CD4-Cre Bbs4FL/FL OT-I Rag2KO/KO (Bbs4 cKO, OT-I) littermates were adoptively transferred into RIP.OVA mice followed by infection with Listeria monocytogenes expressing ovalbumin (LM-OVA) on the next day. (E) Glucose level in the urine of mice was monitored on a daily basis. The mouse was considered diabetic when it had urine glucose level ≥ 1000 mg/dL for two consecutive days. Statistical significance was calculated by Log-rank (Mantel-Cox) test.",
    "ncbi_link": "Bbs4: 102774
CD4: 12504
Cre: 2777477
OVA: 396058
ovalbumin: 396058
Rag2: 19374"
  },
  {
    "caption": "500 or 1000 T cells isolated from lymph nodes of Bbs4FL/FL OT-I Rag2KO/KO (OT-I) and CD4-Cre Bbs4FL/FL OT-I Rag2KO/KO (Bbs4 cKO, OT-I) littermates were adoptively transferred into RIP.OVA mice followed by infection with Listeria monocytogenes expressing ovalbumin (LM-OVA) on the next day. (F) Glucose concentration in blood on day 7 post-infection. 500 OT-I ctrl (n=13 mice), 500 OT-I Bbs4 cKO (n=13), 1000 OT-I ctrl (n=9), 1000 OT-I Bbs4 cKO (n=11), analyzed in four independent experiments, mean is shown. Statistical significance was calculated using two-tailed Mann-Whitney test.",
    "ncbi_link": "Bbs4: 102774
CD4: 12504
Cre: 2777477
OVA: 396058
ovalbumin: 396058
Rag2: 19374"
  },
  {
    "caption": "Cells isolated from bone marrow of Bbs4FL/FL (control) and Vav-iCre Bbs4FL/FL (cKO) mice were analyzed by flow cytometry. (A) Percentage of B220low in bone marrow. Representative experiment out of four in total is shown. Bbs4FL/FL (n=6 mice), Vav-iCre Bbs4FL/FL (n=9). Representative experiment out of six in total is shown. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all tests. Median is shown.",
    "ncbi_link": "Vav-iCre: 
Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from bone marrow of Bbs4FL/FL (control) and Vav-iCre Bbs4FL/FL (cKO) mice were analyzed by flow cytometry. (B) Percentage of B-cell precursors (B220+, IgM- IgD-) in the bone marrow. Representative experiment out of four in total is shown. Bbs4FL/FL (n=6 mice), Vav-iCre Bbs4FL/FL (n=9). Representative experiment out of six in total is shown. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all tests. Median is shown.",
    "ncbi_link": "Vav-iCre: 
Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from , lymph nodes and spleen of Bbs4FL/FL (control) and Vav-iCre Bbs4FL/FL (cKO) mice were analyzed by flow cytometry. (C) Percentage of CD19+ B cells in spleens and lymph nodes of Vav-iCre Bbs4FL/FL (n=12 mice) and Bbs4FL/FL (n=9) mice, six independent experiments. Representative experiment out of six in total is shown. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all tests. Median is shown.",
    "ncbi_link": "Vav-iCre: 
Bbs4: 102774"
  },
  {
    "caption": "Cells isolated from spleen of Bbs4FL/FL (control) and Vav-iCre Bbs4FL/FL (cKO) mice were analyzed by flow cytometry. D) Percentage of late mature B cells (CD19+, IgM-, IgD+) in spleens of Vav-iCre Bbs4FL/FL (n=12 mice), and Bbs4FL/FL mice (n=9). Representative experiment out of six in total is shown. Statistical significance was calculated using two-tailed Mann-Whitney test, p >0.05 for all tests. Median is shown.",
    "ncbi_link": "Vav-iCre: 
Bbs4: 102774"
  },
  {
    "caption": "(E) Expression of Cxcl12 and Il-7 in the bone marrow from Bbs4+/+ Bbs18+/+ (WT) mice (black circles, n=7 mice), Bbs4+/KO (Het, green circle, n=3), Bbs18+/KO (Het, blue circle, n=3), Bbs4KO/KO (green square, n=5), and Bbs18KO/KO (blue square, n=2) was analyzed by RT-qPCR in five independent experiments. The expression was normalized to Gapdh. The statistical significance of the difference between the BBSome-deficient mice (Bbs4KO/KO and Bbs18KO/KO) and controls were calculated using two-tailed Mann-Whitney test. Median is shown.",
    "ncbi_link": "Bbs18: 100503572
Bbs4: 102774
Cxcl12: 20315
Gapdh: 14433
Il-7: 16196"
  },
  {
    "caption": "(F) MEF cell lines were derived from a single Bbs4+/+ (WT) or a single Bbs4KO/KO embryos. The expression of Cxcl12 in these cell lines was analyzed by RT-qPCR. The expression was normalized to Gapdh and to Bbs4+/+ MEFs (=1) for each experiment. Three biological replicates. One sample t test was used for the statistical analysis.",
    "ncbi_link": "Bbs4: 102774
Cxcl12: 20315
Gapdh: 14433"
  },
  {
    "caption": "(G) Expression of Cxcl12 and canonical-WNT responsive gene Alpl in untreated (NT) ST2 cells, or ST2 cells treated with WNT3A or WNT5A was analyzed by RT-qPCR. The expression was normalized to Gapdh and untreated ST2 sample (=1) for each experiment. Four biological replicates were performed. One sample t test was used for the statistical analysis.",
    "ncbi_link": "Alpl: 11647
Cxcl12: 20315
Gapdh: 14433"
  },
  {
    "caption": "(B Indicated parameters were measured using the blood from 20-21 weeks old Bbs4+/+ (WT) (n=15), Bbs4KO/KO (n=7), and Bbs4GT/GT (n=12) mice. Kruskal-Wallis test with Dunn's Multiple Comparison Post-tests was used for the statistical analysis. Median is shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "Indicated parameters were measured using the blood from 20-21 weeks old Bbs4+/+ (WT) (n=15), Bbs4KO/KO (n=7), and Bbs4GT/GT (n=12) mice. Kruskal-Wallis test with Dunn's Multiple Comparison Post-tests was used for the statistical analysis. Median is shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "G) Indicated parameters were measured using the blood from 20-21 weeks old Bbs4+/+ (WT) (n=15), Bbs4KO/KO (n=7), and Bbs4GT/GT (n=12) mice. Kruskal-Wallis test with Dunn's Multiple Comparison Post-tests was used for the statistical analysis. Median is shown.",
    "ncbi_link": "Bbs4: 102774"
  },
  {
    "caption": "qRT-PCR of mGPDH, myogenin and myosin heavy chain (MyHC) levels during C2C12 myocyte differentiation",
    "ncbi_link": "GPDH: 14571
MyHC: 17879
myosin heavy chain: 17879
myogenin: 17928"
  },
  {
    "caption": "Representative images of MyHC immunofluorescence (E) of C2C12 myocyte transfected with the siRNA or the overexpression plasmid for mGPD",
    "ncbi_link": "GPD: 14571"
  },
  {
    "caption": "C2C12 myocyte transfected with the siRNA or the overexpression plasmid for mGPDH; the fusion index (F) and the distribution of nuclei per myotube (G) were calculated at day 5 after differentiation.",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Immunoblot of mGPDH, myogenin and MyHC in C2C12 myocytes transfected with siRNA targeting mGPDH. Quantificatio represents the levels of indicated protein normalized to β-actin at indicated day after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "myogenin and MyHC in C2C12 myocytes transfected with siRNA targeting mGPDH. Quantificatio represents the levels of indicated protein normalized to β-actin at indicated day after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "qRT-PCR analysis of mGPDH, myogenin and MyHC in C2C12 myocytes transfected with the siRN for mGPDH at day 4 after differentiation",
    "ncbi_link": "GPDH: 14571
MyHC: 17879
myogenin: 17928"
  },
  {
    "caption": "qRT-PCR analysis of mGPDH, myogenin and MyHC in C2C12 myocytes transfected wit overexpression plasmid for mGPDH at day 4 after differentiation",
    "ncbi_link": "GPDH: 14571
MyHC: 17879
myogenin: 17928"
  },
  {
    "caption": "qRT-PC  of mGPDH, myogenin and developmental myosin heavy chain (myh8, myl4 and myh3) in gastrocnemius (GA) muscle from C57BL/6J mice at indicated day after CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571
myh3: 17883
myh8: 17885
myl4: 17896
myogenin: 17928"
  },
  {
    "caption": "Representative images of the H&E staining (arrowhead, necrotic myofibers; asterisks, regenerating fibers) (D), distribution of the fibers cross-section area (CSA) (E), percentage of myofibers with central nuclei (F) in GA muscle from WT and mGPDH-/- mice at day 7 post CTX injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "immunofluorescence staining of desmin (green) (G) in GA muscle from WT and mGPDH-/- mice at day 7 post CTX injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Muscle weight (H in GA muscle from WT and mGPDH-/- mice at day 14 post CTX injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "trichrome staining (I) in GA muscle from WT and mGPDH-/- mice at day 14 post CTX injection. Quantification represents the fibrotic areas",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "qRT-PCR (J for mGPDH, myogenin and myh3 in GA muscle from WT and mGPDH-/- mice at day 7 post CTX injection",
    "ncbi_link": "GPDH: 14571
myh3: 17883
myogenin: 17928"
  },
  {
    "caption": "immunoblot (K) for mGPDH, myogeni in GA muscle from WT and mGPDH-/- mice at day 7 post CTX injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "qRT-PCR for mGPDH, myogenin and myh3 (L) in GA muscle from mdx mice 4 weeks after AAV-mGPDH intramuscular injection",
    "ncbi_link": "mdx: 13405
GPDH: 14571
myh3: 17883
myogenin: 17928"
  },
  {
    "caption": "H&E staining (M), distribution of the fibers CSA (N in GA muscle from mdx mice 4 weeks after AAV-mGPDH intramuscular injection",
    "ncbi_link": "mdx: 13405
GPDH: 14571"
  },
  {
    "caption": "), qRT-PCR (O in GA muscle from mdx mice 4 weeks after AAV-mGPDH intramuscular injection",
    "ncbi_link": "mdx: 13405
GPDH: 14571"
  },
  {
    "caption": "immunofluorescence staining (P) for utrophi in GA muscle from mdx mice 4 weeks after AAV-mGPDH intramuscular injection",
    "ncbi_link": "mdx: 13405
GPDH: 14571"
  },
  {
    "caption": "trichrome staining (Q) in GA muscle from mdx mice 4 weeks after AAV-mGPDH intramuscular injection",
    "ncbi_link": "mdx: 13405
GPDH: 14571"
  },
  {
    "caption": "Exercise capacity of mdx mice 6 weeks after AAV-mGPDH tail vein injection.",
    "ncbi_link": "mdx: 13405
GPDH: 14571"
  },
  {
    "caption": "Mitochondrial DNA (A) in C2C12 myocytes transfected with siRNA or plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "nuclear-encoded OXPHOS genes (B in C2C12 myocytes transfected with siRNA or plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "respirometry analysis (C in C2C12 myocytes transfected with siRNA or plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "immunoblots of mGPDH, phospho-Thr172 AMPK (p-AMPK), total AMPK (AMPK), phospho-Ser79-ACC (p-ACC), total ACC and PGC1α and corresponding quantifications represent mGPDH, p-AMPK, p-ACC and PGC1α protein level in C2C12 myocytes transfected with siRN for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "immunoblots of mGPDH, phospho-Thr172 AMPK (p-AMPK), total AMPK (AMPK), phospho-Ser79-ACC (p-ACC), total ACC and PGC1α and corresponding quantifications represent mGPDH, p-AMPK, p-ACC and PGC1α protein levels (D-F) in C2C12 myocytes transfecte wit plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Immunoblots of p-AMPK, p-ACC and PGC1α and corresponding quantifications represent p-AMPK, p-ACC and PGC1α protein levels (G in C2C12 myocytes transfected by mGPDH plasmid with the AMPK inhibitor compound C (CC) 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "mitochondrial DNA (H in C2C12 myocytes transfected by mGPDH plasmid with the AMPK inhibitor compound C (CC) 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "nuclear-encoded OXPHOS genes combined by NDUFS8, SDHb, Uqcrc1, COX5b and ATP5a1 (I) in C2C12 myocytes transfected by mGPDH plasmid with the AMPK inhibitor compound C (CC) 24 h after differentiation",
    "ncbi_link": "ATP5a1: 11946
COX5b: 12859
GPDH: 14571
NDUFS8: 225887
SDHb: 67680
Uqcrc1: 22273"
  },
  {
    "caption": "NAD+/NADH ratio (J in C2C12 myocytes transfected with siRNA or plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "immunoprecipitation analysis for PGC-1α acetyl-lysine (Ac-Lys) level (K) in C2C12 myocytes transfected with siRNA or plasmid for mGPDH 24 h after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Immunoblot of c-myc and myogenin (L in C2C12 myocytes transfected with mGPDH plasmid with the AMPK inhibitor CC at 24 h (L,M after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "corresponding quantifications represent c-myc and myogenin protein levels (M) in C2C12 myocytes transfected with mGPDH plasmid with the AMPK inhibitor CC at 24 h (L,M",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "representative images of MyHC immunofluorescence (N), fusion index (O) and the distribution of nuclei per myotube (P) in C2C12 myocytes transfected with mGPDH plasmid with the AMPK inhibitor CC a 72 h (N-P) after differentiation",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Immunoblots of p-AMPK, p-ACC, PGC1α and myogenin in C2C12 myocytes transfected with mGPDH plasmid with the CaMKKβ inhibitor STO-609 at 24 h after differentiation. Quantifications represent p-AMPK, p-ACC, PGC1α and myogenin protein levels",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Immunoblots of p-AMPK and p-ACC in C2C12 myocytes transfected with mGPDH plasmid with the Ca2+ chelator BAPTA-AM at 24 h after differentiation. Quantifications represent p-AMPK and p-ACC protein levels.",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "qRT-PCR of mGPDH in GA muscle of indicated mice at days 0 and 3 post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Experimental setup (upper of E), qRT-PCR of mGPDH, myogenin and myh3 (bottom of E in GA muscle from AAV-mGPDH-treated HFD-fed mice at days 7 post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571
myh3: 17883
myogenin: 17928"
  },
  {
    "caption": "), H&E staining (arrowhead, necrotic myofibers; asterisks, regenerating fibers) (F), distribution of the fiber CSA (G) in GA muscle from AAV-mGPDH-treated HFD-fed mice at days 7 post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "percentage of myofibers with central nuclei (H) in GA muscle from AAV-mGPDH-treated HFD-fed mice at days 7 post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "Experimental setup (upper of I qRT-PCR of mGPDH, myogenin and myh3 (bottom of I) in GA muscle from AAV-mGPDH-treated STZ-treated mice at day post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571
myh3: 17883
myogenin: 17928"
  },
  {
    "caption": "H&E staining (arrowhead, necrotic myofibers; asterisks, regenerating fibers) (J) in GA muscle from AAV-mGPDH-treated STZ-treated mice at day post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "distribution of the fibers CSA (K), percentage of myofibers with central nuclei (L in GA muscle from AAV-mGPDH-treated STZ-treated mice at day post CTX intramuscular injection",
    "ncbi_link": "GPDH: 14571"
  },
  {
    "caption": "D) UMAP feature plots displaying the normalized expression of CD4, CD8A and CD8B genes. Data information: Each dot represents one cell.",
    "ncbi_link": "CD4: 920
CD8A: 925
CD8B: 926"
  },
  {
    "caption": "B) UMAP feature plots displaying the normalized expression of CD4, CD8A and CD8B genes. Data information: Each dot represents one cell.",
    "ncbi_link": "CD4: 920
CD8A: 925
CD8B: 926"
  },
  {
    "caption": "B) Feature plots of IFI44L expression levels in each patient at early diagnosis in muscle T cells (upper panel) and peripheral blood memory T cells (lower panel). Data information: IMNM: Immune-Mediated Necrotizing Myopathy; DM: DermatoMyositis ASyS: AntiSYnthetase Syndrome; IBM: Inclusion Body Myositis;",
    "ncbi_link": "IFI44L: 10964"
  },
  {
    "caption": "C) MiNA analysis of HeLa cells stained with the membrane potential-independent dye MitoTracker™Green (MTG, 100 nM) to visualize and determine the mitochondrial area (= mitochondrial footprint). Left: HeLa WT cells grown in 10 mM galactose stained with 7 nM TMRE (red) plus 100 nM MTG (green). Co-localization shown in yellow. Right: mitochondrial footprint (white) and mitochondrial skeleton (red) generated from MiNA analysis of the MTG channel (green). D) Left: HeLa IF1-KO cells grown in 10 mM galactose stained with 7 nM TMRE (red) plus 100 nM MTG (green). Right: mitochondrial footprint (white) and mitochondrial skeleton (red) generated from MiNA analysis of the MTG channel (green). E) Left: HeLa IF1-H49K cells grown in 10 mM galactose stained with 7 nM TMRE (red) plus 100 nM MTG (green). Right: mitochondrial footprint (white) and mitochondrial skeleton (red) generated from MiNA analysis of the MTG channel (green). Co-localization shown in yellow. Scale bars = 10 µm. F)",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "A) BN-PAGE and subsequent immuno-blotting of mitochondrial extracts from indicated HeLa cell lines showing the assembly of F1FO ATP synthase and binding of IF1. Monomers (M), dimers (D) and oligomers (O) were detected. Left panel: Coomassie-stained gel. Right panels: Immunoblotting and detection of ATP synthase and IF1. WT: wild type HeLa cells; IF*: cells expressing IF1-H49K. Stars indicate oligomeric IF1 forms. I: complex I; III: complex III.",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "A) Mitochondrial pH at CV SU e measured in HeLa WT in glycolytic (HGlc) and respiring (Gal) conditions. Where indicated, 5 µg/mL oligomycin was added to inhibit CV activity. B) Mitochondrial pH at CV SU e in IF1-KO cells. Conditions: glycolytic (HGlc) and respiring (Gal) with and without oligomycin. C) Mitochondrial pH at CV SU e in IF1-OE cells. Conditions: glycolytic (HGlc) and respiring (Gal) with and without oligomycin. D)",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "F) Effect of inhibiting the respiratory chain at complex III (CIII) with antimycin A (AA) on the local pH at SU e in WT cells (glycolytic conditions). G) Local pH at SU e in IF1-KO cells after inhibiting CIII. H) Local pH at SU e in IF1-OE cells after inhibiting CIII. Da",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "A) Mitochondrial pH at CV SU e is compared for HeLa WT, IF1-KO and IF1-H49K cells under glycolytic and respiring conditions.",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "D) pH at respiratory complex IV at SU CoxVIIIa in the ICS measured in HeLa WT, IF1-KO and IF1-H49K cells under glycolytic and respiring conditions.",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "J) pH measurements in mitochondria in live cells expressing sEcGFP as the pH sensor at SU γ. The pH was color coded according to respective emission ratio. The pH at SU γ in IF1-H49K-expressing cells is compared with WT cells. (Scale bar: 1 µm).",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "A) Mitochondrial ATP production rates in HeLa cells the presence and absence of IF1. Oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) were determined with an automatic flux analyzer (Seahorse/Agilent). After monitoring basal respiration, oligomycin (1 µM), and rotenone plus antimycin A (Rot; 0.5 µM; AA, 0.5 µM) were added sequentially to determine glycolytic and mitochondrial ATP production rates. ~12 technical replicates per measurement, N=4 independent assays.",
    "ncbi_link": "IF1: 93974"
  },
  {
    "caption": "(O) Expression analysis of the β-catenin target gene Axin2 by RNAScope in situ hybridization on neocortex sections from E13.5 control and DKO embryos. Scale bar 20 μm. (P) Quantification of (O). Axin2+ area was calculated and normalized to total neocortex area. Data are expressed as fold change vs. controls and are means ± SEM (n=4 embryos, 3 litters).",
    "ncbi_link": "Axin2: 12006"
  },
  {
    "caption": "(E, F) In utero electroporation (IUE) of plasmids expressing GFP plus shControl (Co) or shCcny/l1 into the lateral ventricles of E13.5 wildtype embryos, followed by analysis at E15.5 or E17.5. (E) IF for GFP and Tbr2 in the E15.5 neocortex. (F) IF for GFP and the deep- layer neuron marker CTIP2 in the E17.5 neocortex. (E, F) White arrowheads denote double-positive cells. Insets of magnified cells (indicated by blue arrowheads) depict representative GFP + Tbr2 (E) or GFP + Ctip2 (F) co-staining. Scale bars 20 μm. (G) Quantification of the percentage of GFP+ cells that are Tbr2+, in control and shCcny/l1 neocortices at E15.5 upon IUE at E13.5. Data are means ± SEM (n=3 embryos). (H) Quantification of the percentage of GFP+ cells that are Ctip2+, in control and shCcny/l1 neocortices at E17.5 upon IUE at E13.5. Data are means ± SEM (n=4 embryos).",
    "ncbi_link": "Ccny: 67974"
  },
  {
    "caption": "(I) IF for βIII-tubulin (Tuj1) of control (Ccny+/-; Ccnyl1-/-; shRNA Co) and mutant (Ccny+/-; Ccnyl1-/-; shRNA Ccny) NPC monolayer cultures grown in differentiation medium for seven days. Insets depict neurons with representative neurite morphology for controls and mutants. Scale bar 20 μm. (J) Quantification of the percentage of Tuj1+ cells from (I). Data are means ± SEM (experiment performed twice in triplicates, representative experiment shown).",
    "ncbi_link": "Ccny: 67974
Ccnyl1: 227210"
  },
  {
    "caption": "(G) Co-transfection of myc-tagged GSK3β and Flag-Sox4 in 293T cells. BIO treatment (0.5 µM) performed for 1 hour prior to harvest. Lower band (65kDa) represents non-phosphorylated Sox4. High and low exposure (exp) blots shown to better visualize non-phosphorylated Sox4. Numbers above blot are quantification of Sox4 protein levels normalized to GFP and are expressed as fold change vs. controls. The sum of upper and lower bands was quantified (n=8 biological replicates).",
    "ncbi_link": "myc: 
GSK3β: 2932"
  },
  {
    "caption": "(B) IF for Tuj1 and Map2 (not shown) to identify newly formed neurons in NPCs after seven-day culture in differentiation medium. Empty CAG-IRES-EGFP vector was used as control in cells not transduced with Sox4/11. Transduced cells were identified by IF for GFP (Co and DKO) or FLAG (Co + Sox4/11 and DKO + Sox4/11). Arrowheads indicate mature neurons and asterisks denote immature neurons lacking neurite extension. Scale bar 20 μm. (C) Quantification of transduced Tuj1+ cells from (B). Note the decrease in neuron number in DKO cultures compared to control, and the rescue in DKO cultures upon Sox4/11 expression (experiment performed twice in triplicates, representative experiment shown). Data are means ± SEM.",
    "ncbi_link": "Sox4: 20677"
  },
  {
    "caption": "A Purified TAP-tagged Rik1-containing complexes analyzed by SDS-PAGE and silver staining. mock: a mock purification from an untagged strain. Proteins identified by LC-MS/MS are indicated at right, with the number of identified unique peptides in parentheses.",
    "ncbi_link": "Rik1: 2539050"
  },
  {
    "caption": "C Ubiquitylation assay using biotinylated ubiquitin and recombinant wild-type H3N-GST (WT) and arginine-substituted H3N-GST mutants as substrates. Proteins were analyzed by Western blotting and silver staining. mock: reaction without substrate. Asterisks indicate ubiquitylated H3N-GST proteins.",
    "ncbi_link": "GST: 
H3N: 2542467"
  },
  {
    "caption": "B Heterochromatic silencing assays of wild-type and mutant Hht1-FH strains. Silencing at the mating-type Kint2::ura4+ was evaluated. Ten-fold serial dilutions of the indicated strains were spotted onto non-selective medium (N/S), medium lacking uracil (-Ura), and medium containing 5-FOA (5-FOA).",
    "ncbi_link": "Hht1: 2542467
ura4: 2538768"
  },
  {
    "caption": "E Heterochromatic silencing assays comparing the effects of H3 lysine substitution mutants. Silencing at the mating-type kint2::ura4+ was evaluated",
    "ncbi_link": "ura4: 2538768"
  },
  {
    "caption": "F Whole cell lysates prepared from control cells, cells expressing FLAG-tagged wild-type Clr4 (F-clr4) or mutant Clr4 (F-clr4∆63-127), or clr4∆ cells were subjected to immunoblotting using the indicated antibodies.",
    "ncbi_link": "FLAG: 
Clr4: 2540825
clr4: 2540825"
  },
  {
    "caption": "G Heterochromatic silencing assays of wild-type and clr4 mutant strains. Silencing at the mating-type Kint2::ura4+ was evaluated.",
    "ncbi_link": "clr4: 2540825
ura4: 2538768"
  },
  {
    "caption": "H ChIP analysis of H3K9me2 levels associated with the silencing marker gene inserted in the mating-type loci (Kint2::ura4+) and the mating-type cenH and centromeric dg loci, relative to the control act1+ locus. Error bars indicate standard errors from three technical replicates.",
    "ncbi_link": "ura4: 2538768"
  },
  {
    "caption": "I The levels of Kint2::ura4+, mating-type cenH, and centromeric dg transcripts were quantified by RT-qPCR and calculated as fold change to the wild-type expression. Error bars indicate standard errors from three technical replicates.",
    "ncbi_link": "ura4: 2538768"
  },
  {
    "caption": "(D) U2OS (EGFP-BIR-5085) cells expressing shRNAs for RAD51, POLD3 or shRNA vector (Ctrl) were infected by lentiviruses encoding endonuclease I-SceI. The percentage of EGFP positive cells was assayed by FACS analysis 4 days later (left). Expression of RAD51 and POLD3 is shown by Western blot analysis (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01, ****P < 0.0001 and n.s. (not significant) P>0.05.",
    "ncbi_link": "EGFP: 
endonuclease I: 
SceI: 
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(B) U2OS WT or PIF1-KO cells were labeled with CldU for 30 min followed by incubation with 2 mM HU for 2 hr and then IdU for another 30 min. Labeled cells were processed for DNA fiber analysis. Representative images of stalled or restarted forks and forks with new origin firing were shown (left). The percentage of restarted forks was quantified by analyzing of 110-130 fibers for each experiment (right). Experiments were repeated four times for each sample. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01, ***P < 0.001.",
    "ncbi_link": "PIF1: 80119"
  },
  {
    "caption": "(D) U2OS (EGFP-BIR-5085) cell lines carrying Dox-inducible Cas9/sgRNA-5085 (Dox-Cas9) or Cas9n/sgRNA-5085 (Dox-Cas9n) were incubated with or without Dox (5 µg/ml) and assayed by FACS analysis 2 days later (left). U2OS (EGFP-BIR-5085, Dox-Cas9 or Dox-Cas9n) cells expressing shRNAs RAD51, POLD3 and PIF1 or shRNA vector (Ctrl) were incubated with 5 µg/ml Dox, and FACS analysis was performed after 2 days (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01, ***P < 0.001.",
    "ncbi_link": "EGFP: 
Cas9: 57852564
Cas9n: 57852564
PIF1: 80119
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(E) U2OS (EGFP-Flex1-BIR-5086) cells expressing shRNAs for RAD51, POLD3 and PIF1 or shRNA vector (Ctrl) were infected by retroviruses expressing RAS, and the percentage of EGFP positive cells was quantified by FACS analysis 4 days after retrovirus infection (top). Expression level of RAD51 and POLD3 is shown by Western blot analysis (bottom). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01.",
    "ncbi_link": "EGFP: 
Flex1: 
PIF1: 80119
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(F) U2OS WT or PIF1-KO cells were infected by retrovirus expressing RAS or empty vector. Cell profiling was plotted by counting cell numbers every 24 hr, and normalized to the cell number on the first day. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01.",
    "ncbi_link": "RAS: 3845
PIF1: 80119"
  },
  {
    "caption": "(C) U2OS (EGFP-STGC-1731) cell lines carrying Dox-inducible Cas9/sgRNA-1731 (Dox-Cas9) or Cas9n/sgRNA (Dox-Cas9n) were incubated with or without Dox (5 µg/ml), and the percentage of EGFP positive cells was quantified by FACS analysis 2 days later (top). U2OS (EGFP-STGC-1731, Dox-Cas9 or Dox-Cas9n) cells expressing shRNAs for RAD51, POLD3 and PIF1 or shRNA control (Ctrl) were incubated with Dox (5 µg/ml), and the percentage of EGFP positive cells was quantified by FACS analysis after 2 days (bottom). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "Cas9: 57852564
Cas9n: 57852564
PIF1: 80119
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(E) U2OS (EGFP-Flex1-STGC-1541) cells were treated with or without 2 mM HU for 24 hr, and the percentage of EGFP positive cells by HU induction was quantified by FACS analysis 4 days after removal of HU (left). U2OS (EGFP-Flex1-STGC-1541) cells expressing shRNAs for RAD51, POLD3 and PIF1 or shRNA vector (Ctrl) were treated with 2 mM HU for 24 hr, and the percentage of EGFP positive cells was quantified by FACS analysis 4 days later (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "Flex1: 
PIF1: 80119
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(F) U2OS (EGFP-Flex1-STGC-1541) cells were infected by retroviruses expressing RAS or empty vector, and the percentage of EGFP positive cells was assayed by FACS 5 days following infection (left). U2OS (EGFP-Flex1-STGC-1541) cells expressing shRNAs for RAD51, POLD3 and PIF1 shRNAs or shRNA vector were infected by retroviruses expressing RAS, and the percentage of EGFP positive cells was assayed by FACS 5 days after infection (middle). Expression level of RAD51 and POLD3 is shown by Western blot analysis (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "Flex1: 
RAS: 3845
PIF1: 80119
POLD3: 10714
RAD51: 5888"
  },
  {
    "caption": "(D) U2OS (EGFP/STGC-mCherry/LTGC-5034, Dox-Cas9 (left) or Dox-Cas9n (right)) cells expressing shRNAs for POLD3 and PIF1 or shRNA vector (Ctrl) were incubated with Dox (5 µg/ml). The percentage of EGFP or mCherry positive cells after induction was quantified by FACS analysis 2 days later to determine the percentage of EGFP or mCherry positive cells. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "mCherry: 
Cas9: 57852564
Cas9n: 57852564
PIF1: 80119
POLD3: 10714"
  },
  {
    "caption": "(E) U2OS (EGFP-Flex1-STGC-1541) cells expressing shRNAs for RFC1 and PCNA or vector (Ctrl) were treated with 2 mM HU for 24 hr. The percentage of EGFP positive cells after HU treatment was quantified by FACS analysis 3 days after HU removal (left). U2OS (EGFP-STGC-1731) cells expressing shRNAs for RFC1 and PCNA or vector (Ctrl) were infected by lentivirus expressing I-SceI. The percentage of EGFP positive cells by I-SceI induction was quantified by FACS analysis 4 days later (right). Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "Flex1: 
PCNA: 5111
RFC1: 5981"
  },
  {
    "caption": "(F) U2OS (EGFP/STGC-mCherry/LTGC-5034, Dox-Cas9 (left) or Dox-Cas9n (right)) cells expressing shRNAs for RFC1 and PCNA or vector (Ctrl) were incubated with Dox (5 µg/ml). The percentage of EGFP or mCherry positive cells after induction was quantified by FACS analysis 2 days later. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "EGFP: 
mCherry: 
Cas9: 57852564
Cas9n: 57852564
PCNA: 5111
RFC1: 5981"
  },
  {
    "caption": "(G) FLAG-PIF1 was stably expressed in U2OS (EGFP-Flex1-STGC-1541) cells by lentiviral infection. Enrichment of FLAG-PIF1 at Flex1 site or GAPDH site with or without HU (2 mM, 10 hr) treatment was calculated by anti-FLAG ChIP (left). When PCNA was depleted by shRNA using vector as a control (Ctrl), enrichment of FLAG-PIF1 at Flex1 site was calculated by anti-FLAG ChIP (right). ChIP value in cells without HU treatment is set up as 1 for normalization. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01 and n.s. (not significant) P>0.05.",
    "ncbi_link": "EGFP: 
FLAG: 
Flex1: 
PCNA: 5111"
  },
  {
    "caption": "(D) Growth curves of WT or FANCM-KO HCT116 cells were plotted after expressing POLD3 (left) or PIF1 (right) shRNA or shRNA vector (Ctrl). Cell number was normalized to that on day one. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as **P < 0.01. ",
    "ncbi_link": "FANCM: 57697
PIF1: 80119
POLD3: 10714"
  },
  {
    "caption": "(C) Anti-γH2AX ChIP analysis at FRA3B, FRA16D and GAPDH genomic loci was performed in U2OS WT and PIF1-KO cells before and after APH treatment (0.4 μM, 24 hr). Enrichment of γH2AX at FRA3B, FRA16D and GAPDH loci in WT and PIF1 KO cells was calculated using ChIP value in WT cells as 1 for normalization. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as *P < 0.05, **P < 0.01, ***P < 0.001 and n.s. (not significant) P>0.05.",
    "ncbi_link": "FRA16D: 2463
GAPDH: 2597
FRA3B: 107325936
PIF1: 80119"
  },
  {
    "caption": "(E) U2OS (EGFP-BIR-5085) cells expressing PIF1 WT or L319P mutant with endogenous PIF1 silenced by shRNA were infected by lentiviruses to express I-SceI. The percentage of EGFP positive cells was quantified by FACS analysis 5 days after I-SceI infection. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as *P < 0.05, **P < 0.01, ***P < 0.001 and n.s. (not significant) P>0.05.",
    "ncbi_link": "I-SceI: 
PIF1: 80119"
  },
  {
    "caption": "(I) Anti-γH2AX ChIP analysis at FRA3B, FRA16D and GAPDH genomic loci was performed in U2OS WT and PIF1-KO cells, or PIF1-KO cells expressing PIF1-WT, and E307Q and L319P mutants before and after APH treatment (0.4 μM, 24 hr). Enrichment of γH2AX at FRA3B, FRA16D and GAPDH loci was calculated using ChIP value in WT cells as 1 for normalization. Data information: Error bars represent the standard deviation (SD) of at least three independent experiments. Significance of the differences was assayed by Two-tailed non-paired parameters were applied in Student's t-test. The P value is indicated as *P < 0.05, **P < 0.01, ***P < 0.001 and n.s. (not significant) P>0.05. ",
    "ncbi_link": "FRA16D: 2463
GAPDH: 2597
FRA3B: 107325936
PIF1: 80119"
  },
  {
    "caption": "(B) Expression of CH25H in heathy donors and COVID-19 patients. The box plot shows the expression of CH25H in macrophages of bronchoalveolar lavage fluids from three healthy donors, three moderate COVID-19 patients and six severe COVID-19 patients by scRNA-seq analysis (Liao et al., 2020).",
    "ncbi_link": "CH25H: 9023"
  },
  {
    "caption": "25HC inhibits membrane fusion mediated by SARS-CoV-2 S (F) 293FT or Vero cells were treated with EtOH or 25HC (5 µM) for 16h prior to transfection with pLVX plasmids encoding SARS-CoV-2 S (F) in the absence of EtOH or 25HC. At 24h post-transfection, syncytium formation was visualized by fluorescence microscopy. White arrows indicate syncytia. Quantification of membrane fusion was performed by calculating the percentages of nuclei involved in syncytia formation from all nuclei in GFP positive cells.",
    "ncbi_link": "S: 43740568"
  },
  {
    "caption": "25HC inhibits membrane fusion mediated by , SARS-CoV S (G, left), and MERS-CoV S (G, right). 293FT or Vero cells were treated with EtOH or 25HC (5 µM) for 16h prior to transfection with pLVX plasmids encoding , SARS-CoV S (G, left), and MERS-CoV S (G, right) in the absence of EtOH or 25HC. At 24h post-transfection, syncytium formation was visualized by fluorescence microscopy. Scale bar, 50 μm. White arrows indicate syncytia. Quantification of membrane fusion was performed by calculating the percentages of nuclei involved in syncytia formation from all nuclei in GFP positive cells.",
    "ncbi_link": "S: 1489668
S: 14254594"
  },
  {
    "caption": "A) Immunoblot and immunofluorescence staining of BCL7A (red) in eNPCs isolated from Bcl7awt/wt (wt) and Bcl7ako/ko (ko) embryos (E13.5). Nestin (green) was used as NPC marker, whereas DAPI (blue) was used to stain nuclei.",
    "ncbi_link": "Bcl7a: 77045"
  },
  {
    "caption": "B) Immunoblot and immunofluorescence staining of BCL7A in smNPCs. Two different BCL7A knockout clones (KO1 and KO2) were used along with the parental (P) cell line.",
    "ncbi_link": "BCL7A: 605"
  },
  {
    "caption": "E-G) BCL7A KO and wt smNPCs were used for (F) nuclear isolation followed by density sedimentation Top panels show representative immunoblots for selected SWI/SNF/BAF complex subunits and respective densitometries are shown below (n=3 biological replicates).",
    "ncbi_link": "BCL7A: 605"
  },
  {
    "caption": "BCL7A KO and wt smNPCs were used for differential salt extraction. Top panels show representative immunoblots for selected SWI/SNF/BAF complex subunits and respective densitometries are shown below (n=3 biological replicates).",
    "ncbi_link": "BCL7A: 605"
  },
  {
    "caption": "H-I) Heatmaps of SMARCA4/BRG1 and H3K27me3 ChIP-seq in wt and BCL7A KO eNPCs. J) Average density plots for SMARCA4/BRG1 occupancy around the TSS in wt and BCL7A KO eNPCs.",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "K-L) Heatmaps of SMARCA4/BRG1 and H3K27me3 ChIP-seq in parental and BCL7A KO smNPCs. M) Average density plots for SMARCA4/BRG1 occupancy around the TSS in parental and BCL7A KO smNPCs.",
    "ncbi_link": "BCL7A: 605"
  },
  {
    "caption": "A) Immunoblots of spontaneously differentiated wt and BCL7A KO eNPCs. Samples were collected at the indicated differentiation time points. Respective densitometries are shown on the right (n=6-7 biological replicates).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "B) Sholl analysis of β-III tubulin-positive immature wt and BCL7A KO neurons following 7 days of spontaneous eNPC differentiation (n=4 biological replicates, each experiment with 10-15 cells per condition).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "C) Immunofluorescence staining (central panel) and quantification (right panel) of β-III tubulin- and GFAP-positive cells as well as RT-PCR analysis (right panels) of spontaneously differentiated iPSC-derived parental and BCL7A KO smNPCs (n=3-7 biological replicates).",
    "ncbi_link": "BCL7A: 605"
  },
  {
    "caption": "D) Immunofluorescence staining of BCL7A expression in hippocampal sections from adult control and Bcl7afl/fl; Nestin-Cretg/wt mice.",
    "ncbi_link": "BCL7A: 77045
Cre: 2777477
Nestin: 25491"
  },
  {
    "caption": "E) EdU experiments in adult mice. Animals were injected with EdU twice daily for three days and sacrificed 21 days thereafter. Images show immunofluorescence stainings for EdU (green), doublecortin (DCX, white), and S100β (red) in hippocampal brain sections from Bcl7awt/wt; Nestin-Cretgt/wt (as control) and Bcl7afl/fl; Nestin-Cretg/wt mice. Representative EdU+ DCX+ (yellow triangles) or EdU+ S100β+ (yellow asterisk) double-labelled cells are indicated in the insets. Scale bar= 50 μm and 20 μm (for insets).",
    "ncbi_link": "Bcl7a: 77045
Cre: 2777477
Nestin: 25491"
  },
  {
    "caption": "F) Quantification of EdU+ (right panel), EdU+ DCX+ (middle panel) and EdU+ S100β+ (left panel) cells within the hippocampal dentate gyrus (DG) of adult control (n=4) and Bcl7afl/fl; Nestin-Cretg/wt (n=5) animals.",
    "ncbi_link": "Bcl7a: 77045
Cre: 2777477
Nestin: 25491"
  },
  {
    "caption": "G) Immunofluorescence staining for DCX+ cells within the DG region of adult Bcl7afl/fl; Nestin-Crewt/wt (as control) and Bcl7afl/fl; Nestin-Cretg/wt animals. Confocal imaging analysis shows a lower number, misalignment and reduced neuritic complexity of DCX+ labelled cells in BCL7A KO mice compared to controls. Yellow arrows indicate misaligned DCX+ cells.",
    "ncbi_link": "Bcl7a: 77045
BCL7A: 77045
Cre: 2777477
Nestin: 25491"
  },
  {
    "caption": "H) Immunofluorescence staining of BCL7A (red) of hippocampal sections from Bcl7afl/fl; Baf53b-Crewt/wt (as control) and Bcl7afl/fl; Baf53b-Cretg/wt mice.",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "I) Immunofluorescence staining of BCL7A (red) and DCX (green) in hippocampal sections of control and Bcl7afl/fl; Baf53b-Cretg/wt mice. Yellow arrow indicates dividing cells, whereas yellow asterisks mark differentiating immature neurons.",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "J) Immunofluorescence staining for DCX (white) within the DG region of adult control and Bcl7afl/fl; Baf53b-Cretg/wt mice. Representative images show no obvious difference in number, morphology or alignment of DCX+ labelled cells. Quantification of DCX+ labelled cells in control and Bcl7afl/fl; Baf53b-Cretg/wt mice is shown on the right (n=3 per genotype).",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "B-C) Representative Ca2+ measurements in (B) wt vs BCL7A KO cortical neurons (CN, 10 days in vitro) and in (C) smNPC-derived parental and BCL7A KO neurons. Ca2+ changes were detected using Fluo-4 and upon treatment with (B) 50 μM glutamate (final concentration) and (C) 100 μM glutamate (final concentration). Upper right panels report Ca2+ peaks (F) relative to baseline (F0). In B, wt: n=18 cells; ko: n=23 cells (n=2 independent experiments). In C, P: n=27 cells; KO1: n=20 cells; KO2: n=19 cells (n=2 independent experiments).",
    "ncbi_link": "BCL7A: 77045
BCL7A: 605"
  },
  {
    "caption": "E) RT-PCR analysis of FOS expression upon glutamate (100 μM for 10 min) stimulation in smNPC-derived parental and BCL7A KO neurons (n=5-6 biological replicates).",
    "ncbi_link": "BCL7A: 605
FOS: 2353"
  },
  {
    "caption": "F) Immunofluorescence staining of cFos in the dentate gyrus of adult Bcl7afl/fl; Baf53b-Cretg/wt (ko) mice and control (ctr) littermates. Mice were either kept in standard housing conditions (upper images; ctr: n=3 mice; ko: n=3 mice) or exposed to an enriched environment (lower images; ctr: n=3 mice; ko: n=4 mice). Quantification of cFos+ cells are shown below.",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "G-K) Behavioral characterization of Bcl7afl/fl; Nestin-Cretg/wt (ko) mice compared to control (ctr) littermates. Animals were tested for their locomotor activity and coordination in (H) the open field (ctr: n=13 mice; ko: n=11 mice) and (I) RotaRod test (ctr: n=12 mice; ko: n=7 mice). Cognitive function was assessed in (J) the Y-maze spontaneous alternation task (ctr: n=13 mice; ko: n=11 mice) and (K) fear conditioning paradigm (ctr: n=11 mice; ko: n=10 mice). The percentage of spontaneous alternations and freezing were used as measures for working and long-term memory function, respectively.",
    "ncbi_link": "Bcl7a: 77045
Cre: 2777477
Nestin: 25491"
  },
  {
    "caption": "L-Q) Behavioral characterization of adult Bcl7afl/fl; Baf53b-Cretg/wt (nKO) mice compared to control (nKO) littermates. Locomotor activity and coordination were assessed in (M) the open field (ctr: n=14 mice; nKO: n=12 mice) and (N) RotaRod paradigm (ctr: n=16 mice; nKO: n=12 mice). Cognitive function was tested in (O) the Y-maze (ctr: n=11 mice; nKO: n=11 mice) and (P-Q) Barnes maze test (ctr: n=11 mice; nKO: n=11 mice). The percentage of spontaneous alternations and freezing were used as measures for working and long-term memory function, respectively. Representative heatmaps of Barnes maze test are reported on the right. The time spent in target (T) and non-target quadrants during the probe trial are shown on the right.",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "A) Heatmap of significantly dysregulated genes in BCL7A KO compared to wt eNPCs.",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "F) Immunoblots of spontaneously differentiated wt and BCL7A KO eNPCs in presence of 1 μM DAPT or 3 μM CHIR99021.",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "G) Immunofluorescence staining of eNPCs undergoing spontaneous differentiation for 7 days. BCL7A KO eNPCs were incubated for 72 h (24 h in proliferation plus 48 h in differentiation medium) with DMSO, 1 μM DAPT, 3 μM CHIR99021 or a combination of 1 μM DAPT + 3 μM CHIR99021. Quantification of the β-III tubulin-positive or GFAP-positive cells is shown on the right (n=3-6 technical replicates from 3 independent experiments).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "I) mRNA expression levels of TUBB3 and GFAP at 15 and 25 days of spontaneously differentiating BCL7A KO compared parental smNPCs. BCL7A KO smNPCs were treated with DAPT, CHIR99021, DAPT + CHIR99021 or DMSO (as control= ctr) during the initial 7 days of spontaneous differentiation (n=3-7 biological replicates).",
    "ncbi_link": "BCL7A: 605
GFAP: 2670
TUBB3: 10381"
  },
  {
    "caption": "J) Immunoblots for non-phospho (active) β-catenin and TCF4/TCF7L2 in proliferating and 48 h-differentiated wt and BCL7A KO eNPCs. Respective densitometries are shown on the right (n=5-8 biological replicates per condition).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "G) Proximity ligation assay (PLA) for the OXPHOS subunits NDUFB8 and MTCO1 in adult hippocampal sections from Bcl7afl/fl; Baf53b-Cretg/wt (ko; n=4) and control littermates (ctr; n=4). Sections were co-stained with TOM20 and NeuN to label mitochondria and neurons, respectively. The total number of PLA dots was normalized to the mitochondrial area (panel on the lower right).",
    "ncbi_link": "Baf53b: 83766
Bcl7a: 77045
Cre: 2777477"
  },
  {
    "caption": "A) OCR measurements in wt and BCL7A KO eNPCs treated with 3 μM of CHIR99021 or DMSO (as control, ctr) for 24 h. The average maximal respiration upon FCCP treatment is shown on the right (n= 5-7 biological replicates).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "B) OCR measurements in wt and BCL7A KO eNPCs following 48h of spontaneous differentiation. BCL7A KO eNPCs were treated for 72 h (24 h in proliferation plus 48 h in differentiation medium) with CHIR99021 or DMSO. The average maximal respiration upon FCCP treatment is shown on the right (n= 4 biological replicates).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "C) Immunoblot analysis of differentiated BCL7A KO eNPCs exposed to 3 μM CHIR99021, in presence or absence of 20 nM rotenone (rot). Antibodies against β-III tubulin and actin were used.",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "D) Immunofluorescence staining of spontaneously differentiated eNPCs. BCL7A KO eNPCs were treated for 72 h (i.e., 24 h in proliferation plus 48 h in differentiation medium) with 3 μM CHIR99021, in presence or absence of 20 nM rotenone. Scale bar= 50 μm. Statistics are shown on the right (n=3-6 technical replicates from 3 independent experiments).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "E) Sholl analysis of β-III tubulin-positive immature neurons following 7 days of spontaneous differentiation. BCL7A KO eNPCs were exposed to 3 μM CHIR99021, in presence or absence of 20 nM rotenone (n=3 biological replicates).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "F) Representative OCR measurements in BCL7A KO eNPCs treated with 5 and 10 μM of pioglitazone or DMSO (as control, ctr) for 24 h. The average maximal respiration upon FCCP treatment is shown on the right (n= 3 biological replicates).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "G) Immunofluorescence staining of spontaneously differentiated eNPCs. BCL7A KO eNPCs were treated for 72 h (i.e., 24 h in proliferation plus 48 h in differentiation medium) with 5 μM pioglitazone. The percentage of β-III-tubulin-positive cells is shown on the right (n=3-8 technical replicates from 2 independent experiments).",
    "ncbi_link": "BCL7A: 77045"
  },
  {
    "caption": "B) Five-fold serial dilutions of strains of the indicated genotypes (wt cells and choppΔ cells harboring empty vectors or choppΔ cells expressing chimeric Psd and Pmt enzymes). Cells were grown on SD-HIS-LEU (-HL) medium (KennedyOFF) or SD-HL containing ethanolamine and choline (KennedyON).",
    "ncbi_link": "Pmt: 
Psd: 853080///855552"
  },
  {
    "caption": "C) Thin layer chromatography (TLC) analysis of steady-state phospholipid profiles of cells of the indicated genotypes. Where Psd and/or Pmt are missing (-), choppΔ cells were grown in the presence of ethanolamine and/or choline. Bands corresponding to the phospholipids PA, PS, PE, PI and PC are indicated.",
    "ncbi_link": "Pmt: 
Psd: 853080///855552"
  },
  {
    "caption": "C) VPS13 is required in KennedyOFF conditions when chimeric enzymes are targeted to mitochondria or endosomes. Volcano plots show the fold change of number of transposon insertions per gene of libraries grown in KennedyOFF versus ON conditions. This comparison included all six libraries where the enzymes are targeted to endosomes and/or mitochondria (top left panel) or six libraries with enzymes targeted to other organelles (bottom left panel). Data-points for VPS13 are highlighted in red. Schematic illustrating Vps13-mediated lipid transport at endosomes and mitochondria contact sites (right panel).",
    "ncbi_link": "VPS13: 850619
Vps13: 850619"
  },
  {
    "caption": "B) Requirement for mitochondrial lipid transport and biosynthesis genes in rewired libraries. Left panel, schematic depicting PE and cardiolipin (CL) synthesis in mitochondria. The inner mitochondrial putative lipid transporter Mdm31 is depicted in yellow. Grey arrows indicate the need for lipid transport from the ER or other organelles to mitochondria and transport between the MOM and MIM. Right panel, transposon numbers (normalized to wt libraries) for the indicated (set of) libraries for MDM31, PGS1, and CRD1.",
    "ncbi_link": "CRD1: 851413
MDM31: 856601
Mdm31: 856601
PGS1: 850352"
  },
  {
    "caption": "B. hTR and hTERT expression, normalized to  ACTB  mRNA and to SW39/TEL+. Data information: Data are presented as mean ± SD. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution unless specified otherwise. PTM, post-translational modification.",
    "ncbi_link": "ACTB: 60
TR: 7012
TERT: 7015"
  },
  {
    "caption": "C. RNA Pol II binding  at hTR promoter in SI14/TEL+, SI24/ALT+ and 8G12/ALT+ cell lines, normalized to H3 ChIP. Control loci with, respectively, high or low transcriptional activity:  c-fos promoter and subtelomeric 4qHox locus (n=3). Statistical analyses were performed using one-way ANOVA with post-hoc Tukey's test for multiple comparisons. Data information: Data are presented as mean ± SD. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution unless specified otherwise. PTM,  post-translational modification.",
    "ncbi_link": "4qHox: 
c-fos: 2353
TR: 7012"
  },
  {
    "caption": "D. H3K9me3 and H3K27me3 (left) or  H3K4me3 and H3Ac (right) densities at hTR promoter in  SI14/TEL+ and SI24/ALT+, normalized to H3 (n=3). Control loci as in C. Data information: Data are presented as mean ± SD. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution unless specified otherwise. PTM, post-translational modification.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "E. NFYB binding at hTR promoter in SI14/TEL+, SI24/ALT+, SW39/TEL+ and  IMRB/ALT+ cells normalized to H3. Control loci with, respectively, high and low NFYB binding: hnRNPA1 promoter and subtelomeric 4qHox (n=3). Data information: Data are presented as mean ± SD. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution unless specified otherwise. PTM, post-translational modification. ",
    "ncbi_link": "4qHox: 
hnRNPA1: 3178
TR: 7012"
  },
  {
    "caption": "B. NHP2  mRNA expression levels, normalized to ACTB mRNA and to SI14/TEL+  cells (n=3). Data information: Data are presented as mean ± SD.",
    "ncbi_link": "ACTB: 60
NHP2: 55651"
  },
  {
    "caption": "D. hTR RNA and NHP2 mRNA expression, normalized to ACTB mRNA and to SI14/TEL+. Data information: Data are presented as mean ± SD.",
    "ncbi_link": "ACTB: 60
NHP2: 55651
TR: 7012"
  },
  {
    "caption": "E. Telomerase activity  measured with ddTRAP assay in  NHP2-overexpressing 8G12/ALT+cells, normalized to  NHP2-overexpressing SI14/TEL+. Data information: Data are presented as mean ± SD.",
    "ncbi_link": "NHP2: 55651"
  },
  {
    "caption": "F. (Top) Western blot for NHP2 overexpression in 8G12/ALT+ clonal cell lines. β-Actin served as loading control. SI14/TEL+ cells are shown as reference for NHP2 expression in hybrids. (Bottom) Western blot for  NHP2 overexpression in SI14/TEL+ and 8G12/ALT+ cells compared to empty vector control. β-Actin served as loading control. Data information: Data are presented as mean ± SD.",
    "ncbi_link": "NHP2: 55651"
  },
  {
    "caption": "G. hTR RNA, hTERT and NHP2 mRNA expression, normalized to ACTB mRNA and to SI14/TEL+ (n=3). Data information: Data are presented as mean ± SD.",
    "ncbi_link": "ACTB: 60
NHP2: 55651
TR: 7012
TERT: 7015"
  },
  {
    "caption": "H. RNA Pol II binding at hTR promoter, normalized to H3 ChIP (n=3). See Fig. 1C legend for control loci. Statistical analyses were performed using one-way ANOVA with post-hoc Tukey's test for multiple comparisons. Data information: Data are presented as mean ± SD.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "A. hTR RNA, hTERT and NHP2 mRNA expression, normalized to ACTB mRNA and to 143B/TEL+ cells, in a series of TEL+ and ALT+ human cell lines as indicated (n=3). Data information: Data are presented as mean ± SD. Statistical analyses were performed using one-way ANOVA with post-hoc Tukey's test for multiple comparisons.",
    "ncbi_link": "ACTB: 60
NHP2: 55651
TR: 7012
TERT: 7015"
  },
  {
    "caption": "A. hTR RNA expression, normalized to ACTB mRNA and to U2OS cells (n=3). Data information: Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "ACTB: 60
TR: 7012"
  },
  {
    "caption": "B. Western blot for  NHP2 expression in the early passages of hTR-expressing  IMRB or U2OS  cells, with  β-Actin as loading control.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "C. Quantification of doubling time for U2OS, U2OS-hTR, IMRB and  IMRB-hTR cell lines (n=3). Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution Data information: Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "D. Western blot in U2OS and U2OS-hTR cells treated with or without Hydroxyurea (2 mM for 24 h), for the indicated proteins. β-Actin  and Vinculin served as loading controls.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "F. Quantification of  live cell numbers with trypan blue staining and manual counting, 72 h post-transfection with siLuc, sihTR#1 or sihTR#2, measured as the percentage of siLuc-treated cells (n=3). On the right, representative  images of U2OS cells treated with sihTR#1 for 72 h. Statistical analyses were performed using one-way ANOVA with post-hoc Tukey's test for multiple comparisons. Data information: Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "Luc: 249591
TR: 7012"
  },
  {
    "caption": "G. Western blot analyses in the indicated cell lines cells transfected for 48 h with siLuc or sihTR, with the indicated antibodies. U2OS  cells treated with Hydroxyurea (2 mM for 24 h) were used as positive controls.",
    "ncbi_link": "Luc: 249591
TR: 7012"
  },
  {
    "caption": "C. Representative images for TIF quantification: co-localization  between 53BP1 (green) and telomeres (red FISH probe) in U2OS or IMRB cells with or without ectopic hTR overexpression. White arrows indicate TIF. Quantification of TIF is on the right. A total of 110-170 nuclei were scored from three independent experiments. Each dot represents the number of TIF per nucleus. Data information: All scale bars: 5 μm. Data are shown as mean ± SD. , C, the red line marks the mean value. Statistical analyses were performed with Student's two-tailed unpaired t-tests with Welch's correction for normality of distribution, unless specified otherwise.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "D. Representative images for TIF quantification, as in (A), in U2OS or U2OS-hTR cells, treated as indicated with DMSO or 5 μM ATRi or 5 μM ATMi for 20 h. White arrows indicate TIF. Data information: All scale bars: 5 μm. Data are shown as mean ± SD.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "H,I. C-circle analyses in the indicated cell lines 72 h after treatment with siPOLD3 or siLuc used as control for transfection. Quantifications are shown below (n=3). siSMARCAL1 was used as positive control for increased C-circle production in cells with defective fork reversal activity (Zhang et al, 2019b). Data information: All scale bars: 5 μm. Data are shown as mean ± SD. ",
    "ncbi_link": "Luc: 249591
POLD3: 10714
SMARCAL1: 50485"
  },
  {
    "caption": "C. Representative images for co-localization between EdU (green) and telomeres (red FISH probe) within PML bodies (cyan) in U2OS and U2OS-hTR cells. White arrows indicate  co-localization events. D, E. Quantification of images shown in (C).  Co-localization events between EdU foci and APBs were analyzed (D) and the percentage of APBs that are actively engaged in G2/M telomeric  synthesis was calculated (E). A total of at least 50 nuclei were scored from three independent experiments. Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution. ",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "D. Representative images for co-localization between RPA32 or p-RPA32S33 (green) and telomeres (red FISH probe), in the indicated cell lines treated with siLuc or sihnRNPA1 for 48 h. White arrows indicate co-localization events. Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value. Statistical analyses were performed with Student's two-tailed unpaired t-test with Welch's correction for normality of distribution unless specified otherwise.",
    "ncbi_link": "hnRNPA1: 3178
Luc: 249591"
  },
  {
    "caption": "A. hTR and NHP2 mRNA expression in U2OS-hTR cells 72 h post-transfection with siLuc or siNHP2, normalized to ACTB mRNA and to SI14/TEL+ cells (n=2). Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "ACTB: 60
Luc: 249591
NHP2: 55651
TR: 7012"
  },
  {
    "caption": "B. Western blot showing NHP2 protein levels in the indicated cells treated with siLuc or siNHP2, 72 h post-transfection. β-Actin served as loading control.",
    "ncbi_link": "Luc: 249591
NHP2: 55651"
  },
  {
    "caption": "C. Representative images for co-localization between p-RPA32S33 (green) and telomeres  (red FISH probe) in U2OS-hTR cells treated with control siLuc or siNHP2, 72 h post-transfection. White arrows indicate co-localization events. Quantification of  images is shown on the right. Each dot indicates the  number of co-localization events per nucleus  (n=2). Statistical analyses were performed with Student's two-tailed unpaired t-tests with Welch's correction for normality of distribution. Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "Luc: 249591
NHP2: 55651
TR: 7012"
  },
  {
    "caption": "D. Representative images for TIF quantification: co-localization between 53BP1  (green) and telomeres (red FISH probe), measured 72 h post-transfection with siLuc or siNHP2 in cells further treated with either DMSO or Doxorubicin (DOXO, 1.5 μM) for 2 h. White arrows indicate TIF. Quantification of TIF is shown on the right. A total of at least 100 nuclei were scored from two independent experiments. Each dot represents the number of TIF per nucleus. Statistical analyses were performed using one-way ANOVA with post-hoc Games-Howell's test for multiple comparisons. Data information: All scale bars: 5 μm. Data are shown as mean ± SD, with the red line marking the mean value.",
    "ncbi_link": "Luc: 249591
NHP2: 55651"
  },
  {
    "caption": "E. Western blot analyses in U2OS and U2OS-hTR cells treated with the indicated siRNAs, 72 h post-transfection to detect total protein levels using the indicated antibodies. β-Actin and Vinculin served as loading controls.",
    "ncbi_link": "TR: 7012"
  },
  {
    "caption": "F. Representative images for 53BP1 foci formation in U2OS and U2OS-hTR cells, 72 h post-transfection with siLuc or siNHP2, exposed to 1 Gy irradiation and fixed at various time points post-irradiation as indicated.",
    "ncbi_link": "Luc: 249591
NHP2: 55651
TR: 7012"
  },
  {
    "caption": "A Growth curves show proliferation reduction in ATRX depleted U87 cells. Data are expressed as means ± standard deviation (s.d.), N = 2. 500 cells/well were plated.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "B β-gal staining revealed the increased senescent cell population in ATRX-deleted U87 cells. Upper panel, micrographs of control and ATRX-deleted U87 cells processed for ATRX immunofluorescence (IF) and β-gal senescence assay. Scale bar, 200 µm. D, DAPI. Lower panel, percentage of senescent cells. Data are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "C, D PML/TelG immuno-FISH (C) shows increased APB formation in ATRX-deleted U87 cells (D). Scale bar, 10 µm. (D) Percentages of APB positive cells are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "E C-circle assays revealed enhanced C-circles formation in ATRX-deleted U87 cells. Reactions lacking DNA or ɸ29 serve as negative controls. 30 ng of indicated template DNA was used in each reaction.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "G 53BP1/TelG immuno-FISH shows increased TIF formation in ATRX-deleted U87 cells (G). Arrows denote telomeres positive for 53BP1 signals. Scale bar, 10 µm. (G) Percentages of cells containing > 4 TIFs are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546"
  },
  {
    "caption": "H Growth curves revealed increase of cell proliferation in ATRX-deleted U87 cells (A-1 and A-2) after hTERT transduction. Data are expressed as means ± s.d., N = 2.",
    "ncbi_link": "ATRX: 546
hTERT: 7015"
  },
  {
    "caption": "I Western blots show depletion of ATRX protein expression in hTERT-transduced and ATRX-deleted A-1 and A-2 U87 cells.",
    "ncbi_link": "ATRX: 546
hTERT: 7015"
  },
  {
    "caption": "A Growth curves revealed that deletion of ATRX had minor effect on proliferation of TERT-overexpressed U87-T cells, but further removal of the exogenous floxed TERT by Ad-Cre induced rapid cell cycle arrest. Data are expressed as means ± s.d., N = 3.",
    "ncbi_link": "ATRX: 546
Cre: 2777477
TERT: 7015"
  },
  {
    "caption": "B Telomere restriction fragment (TRF) analysis shows increased telomeric length heterogeneities in ATRX-deleted U87-T and the further enhancement following Ad-Cre treatment. Genomic DNAs (EtBr staining, left panel) prepared from control and ATRX-deleted U87-T cells at day 9 post control or Ad-Cre infection (middle panel) were assayed by hybridization with 32P-labelled (TTAGGG)4 probe, followed by re-hybridization with an oligonucleotide probe specific for centromere region (right panel). Genomic DNA from U2OS cells was used as an ALT positive control.",
    "ncbi_link": "ATRX: 546
Cre: 2777477"
  },
  {
    "caption": "C, D PML/TelG immuno-FISH (C) shows increased APB formation in ATRX-deleted U87-T cells (D) at day 9 post control or Ad-Cre infection. Images are maximum-intensity projections of ~10 stacks captured with a 63x lens with 2x zoom. Scale bar, 10 µm. (D) Percentages of APB positive cells are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546
Cre: 2777477"
  },
  {
    "caption": "E 2D gel analysis revealed increased T-circle formation in ATRX-deleted U87-T cells without or with Ad-Cre infection. Shown are gels stained with EtBr and blots hybridized with a TelG probe. Indicated are linear (lin) and open (oc) T-circle forms of telomeric DNA.",
    "ncbi_link": "ATRX: 546
Cre: 2777477"
  },
  {
    "caption": "F C-circle assays shows increased C-circle formation in ATRX-deleted U87-T cells at day 9 post control or Ad-Cre infection.",
    "ncbi_link": "ATRX: 546
Cre: 2777477"
  },
  {
    "caption": "G, H 53BP1/TelG immuno-FISH (G) shows increased TIF formation in ATRX-deleted U87-T cells at day 9 post control or Ad-Cre infection (H). Scale bar, 10 µm. (H) Percentages of cells containing > 4 TIFs are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546
Cre: 2777477"
  },
  {
    "caption": "B Western blots of extracts from U87 cells infected with Lenti-CRISPR(puro) encoding individual ATRX-targeted sgRNAs. The extracts were isolated after puromycin selection, and assayed for ATRX depletion levels using antibody against ATRX or ACTIN control. The asterisks (*) denote the two sgATRXs (sgA#10 and sgA#19) used in following experiments.",
    "ncbi_link": "CRISPR: 
ATRX: 546
ATRXs: 546"
  },
  {
    "caption": "C ATRX immunofluorescence staining of U87 cells infected with lentiviral control sgRosa, sgA#10, or sgA#19. D, DAPI. Scale bar, 50 µm.",
    "ncbi_link": "Rosa: 91978"
  },
  {
    "caption": "Bar graphs show time-course analyses of U87 (E) transduced with lentiviral LRG vector encoding sgRosa control or ATRX-targeted sgA#10 or sgA#19. The graph plots the percentage of GFP+ cells over time following transduction with indicated sgRNAs. Data are expressed as means ± s.d., * denotes ns (not significant); **, p < 0.01; ***, p < 0.001. N = 3, unpaired t test.",
    "ncbi_link": "GFP: 
ATRX: 546
Rosa: 91978"
  },
  {
    "caption": "Bar graphs show time-course analyses of U2OS cells (F) transduced with lentiviral LRG vector encoding sgRosa control or ATRX-targeted sgA#10 or sgA#19. The graph plots the percentage of GFP+ cells over time following transduction with indicated sgRNAs. Data are expressed as means ± s.d., * denotes ns (not significant); **, p < 0.01; ***, p < 0.001. N = 3, unpaired t test.",
    "ncbi_link": "GFP: 
ATRX: 546
Rosa: 91978"
  },
  {
    "caption": "K Bar graphs show time-course analyses of IMR90 cells transduced with lentiviral sgRosa, sgA#10 or sgA#19. Data are expressed as means ± s.d., * denotes ns (not significant); **, p < 0.01; ***, p < 0.001. N = 3, unpaired t test.",
    "ncbi_link": "Rosa: 91978"
  },
  {
    "caption": "A, B γH2AX/TelG immuno-FISH (A) revealed increased TIF formation in IMR90 cells transduced with DAXX-targeted lentiviral sgRNAs (sgD#1 and #2) (B). Scale bar, 10 µm. Arrows denote telomeres that are positive for γH2AX signals. (B) Percentage of cells containing > 4 TIFs are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "DAXX: 1616"
  },
  {
    "caption": "C Western blots show depleted DAXX protein expression in Ad-Flp-infected cd-DAXX cells.",
    "ncbi_link": "Flp: 
DAXX: 1616"
  },
  {
    "caption": "D, E PML/TelG immune-FISH (D) show enhanced APB formation in Ad-Flp infected cd-DAXX cells (cd-D#1 and cd-D#2) (E). The cells were analyzed at day 18 post Ad-Flp infection. Images are maximum-intensity projections of ~10 stacks captured with a 63x lens with 2x zoom. Scale bar, 10 µm. (E) Percentages of APB+ cells are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "Flp: 
DAXX: 1616"
  },
  {
    "caption": "Depletion of DAXX induced delayed onset of growth arrest (F) (F) 2,000 cells were plated at day 4 post Ad-Flp infection. Data are expressed as means ± s.d., N = 3.",
    "ncbi_link": "Flp: 
DAXX: 1616"
  },
  {
    "caption": "Depletion of DAXX induced C-circle formation (G).",
    "ncbi_link": "DAXX: 1616"
  },
  {
    "caption": "A Growth curves show the immortalization processes of lentiviral Rosa control (sgRosa#1 or #2) or sgATRX (sgA#10 or #19) transduced IMR90 cells. TERT transduced IMR90 culture was included as a positive control for immortalization.",
    "ncbi_link": "ATRX: 546
TERT: 7015
Rosa: 91978"
  },
  {
    "caption": "B Quantitative RT-PCR of endogenous TERT gene expression revealed that sgATRX but not sgRosa transduced IMR90 cells adopted ALT during immortalization. Data are expressed as means ± s.d., N = 3, unpaired t test.",
    "ncbi_link": "ATRX: 546
TERT: 7015
Rosa: 91978"
  },
  {
    "caption": "A.  Western blot  analysis of LDHA  and LDHB  expression in P3 cells transduced with CRISPR-Cas9 lentiviral  vectors with scramble sequence (sgControl) or against LDHA  (sgLDHA), LDHB  (sgLDHB) or both (sgLDHA/B). Knockout (KO) cells were exposed to 21% or 1% O2  for 48 h.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
LDHA: 3939
LDHB: 3945"
  },
  {
    "caption": "D. Left: P3 spheroid growth  recorded over one week at 1% O2  (n = 3 independent experiments, one experiment including 16 spheroids per condition). Data are represented as mean and analyzed using Kruskal-Wallis test followed by Dunn's multiple comparisons test. Spheroid growth: sgCont vs sgLDHA, P=0.0003; sgCont vs sgLDHB, P=0.78; sgCont vs sgLDHA/B, P<0.0001. Dead area: sgCont vs sgLDHA, P=0.19; sgCont vs sgLDHB, P<0.0001; sgCont vs sgLDHA/B, P<0.0001. Right: Viability  of spheroids  at one week, incubated with calcein (green) or ethidium homodimer-1  (red). Scale bar: 200 µm.",
    "ncbi_link": "LDHA: 3939
LDHB: 3945"
  },
  {
    "caption": "E. P3 spheroid invasion  in collagen  I   gel, incubated 24 h at 21% or 0.1% O2. Invasion rate is expressed as fold change from controls (n = 4 independent experiments, one experiment including 6-8 spheroids  per condition). Data are represented as mean and analyzed using Two-way ANOVA following by Tukey's multiple comparisons test: sgCont 21% vs sgLDHA 21%, P=0.003; sgCont 0.1% vs sgLDHA  0.1%, P<0.0001; sgCont 21% vs sgLDHB  21%, P<0.0001; sgCont 0.1% vs sgLDHB 0.1%, P<0.0001; sgCont 21% vs sgLDHA/B 21%, P<0.0001; sgCont 0.1% vs sgLDHA/B 0.1%, P<0.0001. Images of representative of control or LDHA/B KO spheroids. Scale bar: 100 µm.",
    "ncbi_link": "LDHA: 3939
LDHB: 3945"
  },
  {
    "caption": "F-G. A first cohort of mice  was sacrificed when one mouse  reached a limit point, brains  was extract, snap frozen in liquid nitrogen, sliced and stained. For the second cohort, each mouse was sacrificed when it reached a limit point allowing the draw of survival curves. Left: Immunofluorescence staining  of Nestin  (top and middle) and CD31  (bottom) of control and LDHA/B KO P3 tumor section. Scale bars: 2 mm (top), 250 µm (middle) and 100 µm (bottom). Right: Graphs represent tumor core and invasion  area of control and  LDHA/B KO P3 tumors in mm2 (n = 5 mice  per group, average of 5-6 sections per tumor). Data are represented as mean. For F, data are analyzed using One-way ANOVA following by Dunnett's multiple comparisons test. Core: sgCont vs sgLDHA, P=0.48; sgCont vs sgLDHB, P=0.99. Invasion: sgCont vs sgLDHA, P=0.40; sgCont vs sgLDHB, P=0.81. For G, data are analyzed using unpaired t test. Core: sgCont vs sgLDHA/B, P=0.005. Invasion: sgCont vs sgLDHA/B, P=0.01.",
    "ncbi_link": "LDHA: 3939
LDHB: 3945"
  },
  {
    "caption": "B. Epifluorescence  (top) and quantitative image analysis (bottom) of immune stained mitochondria  (TOM20, green) from LDH KO P3 cells (Phalloidin, red; DAPI, blue) upon exposure to 0.1% O2  (n = 2 independent experiments, 28-32 cells per group). Data are represented as mean and analyzed using One-way ANOVA following by Tukey's multiple comparisons test. Mitochondrial  mass: sgCont vs sgLDHA/B, P=0.005; sgLDHA/sgLDHB vs sgLDHA/B, p=0.006. Network aspect ratio: sgCont vs sgLDHA/B, P=0.03; sgLDHA vs sgLDHA/B, P=0.02; sgLDHB vs sgLDHA/B, p=0.04. Mitochondrial  mass corresponds to the area covered by the mitochondria  relative to the entire cell area. Network aspect ratio is the ratio of the major axis to minor axis of the  mitochondrial network. Scale bar: 10 µm.",
    "ncbi_link": "LDHA: 3939
LDHB: 3945"
  },
  {
    "caption": "E. Kaplan-Meier survival curves of xenotransplanted mice  with LDHA/B KO (red) or control (blue) P3 cells, treated with phenformin  or irradiated  with 10 Gy (n = 6-8 mice  per group). Data are analyzed using Log-rank (Mantel-Cox) test: sgCont Vehicle vs sgCont Phenformin, P=0.019; sgCont Vehicle vs sgCont Irradiation, P=0.0002; sgCont Irradiation vs sgLDHA/B Irradiation, P=0.024.",
    "ncbi_link": "LDHA: 3939"
  },
  {
    "caption": "Statistics of 3H-glutamate uptake by neurons transfected with two lentivirus-based RNAi against EAAC1 (R2 and R3) or nonsense RNAi (Non) in response to vehicle (Ctrl) or Shh (D, n=3-6). No difference between R2 or R3 in Ctrl and those in Shh. Inset of (D): representative western-blots for EAAC1.",
    "ncbi_link": "EAAC1: 25550"
  },
  {
    "caption": "(G) Upper, representative western-blots of EAAC1 and Smo from HEK293 cells transfected with empty vectors (Ctrl), constitutively active form of Smoothened (SmoA1), EAAC1, or EAAC1 plus SmoA1. Lower, 3H-glutamate uptake by cells transfected with the indicated vectors. n=9.",
    "ncbi_link": "EAAC1: 6505
Smo: 6608"
  },
  {
    "caption": "Effects of ablation of Smo in CaMKIIα-positive neurons (G-I), on the progression of kindling including seizure class (A,D,G,J), evoked electrographic seizure duration (ESD) (B,E,H,K) and the number of stimulations required to reach equivalent seizure intensity (C,F,I,L). In G-I, Ctrl: Smofl/fl induced by tamoxifen; CaMK: Smofl/flCaMKIIα-CreERT2 induced by tamoxifen, n=14-20.",
    "ncbi_link": "CaMKIIα: 12322
Smo: 319757"
  },
  {
    "caption": "Effects of ablation of Smo in Aldh1l1-positive astrocytes (J-L) on the progression of kindling including seizure class (A,D,G,J), evoked electrographic seizure duration (ESD) (B,E,H,K) and the number of stimulations required to reach equivalent seizure intensity (C,F,I,L). In J-L, Ctrl: Smo+/fl; Aldh1l1: Smo+/flAldh1l1-Cre, n=19-20.",
    "ncbi_link": "Aldh1l1: 107747
Smo: 319757"
  },
  {
    "caption": "D-E qPCR results showing mRNA expression of CIB1, FT in the genotypes indicated. The numbers indicate independent transgenic lines. The transcript levels of CIB1 or FT in Col were set to 1.0. Samples were collected from 7-day-old LD grown seedlings at ZT16. Data information: error bars indicate standard error within three biological replicates and for each of these two technical replicates were performed.",
    "ncbi_link": "CIB1: 829604
FT: 842859"
  },
  {
    "caption": ", I-J. qPCR results showing mRNA expression of CO, FT in the genotypes indicated. The numbers indicate independent transgenic lines. The transcript levels of CO or FT in Col were set to 1.0. Samples were collected from 7-day-old LD grown seedlings at ZT16. Data information: error bars indicate standard error within three biological replicates and for each of these two technical replicates were performed.",
    "ncbi_link": "CO: 831441
FT: 842859"
  },
  {
    "caption": "Immunoblots showing CIB1 (A) protein levels in WT and co-1 backgrounds (A) over the course of 20 hours under LDs. Samples were separated on 10% SDS-PAGE, blotted, probed with the anti-Myc antibody, stripped and re-probed with the anti-actin antibody (ACT).",
    "ncbi_link": "co: 831441"
  },
  {
    "caption": "The relative levels of CIB1 in WT and co-1 backgrounds over the course of 20 hours under LDs were calculated Data information: Error bars represent the standard deviation of three biological replicates of the Western blots.",
    "ncbi_link": "co: 831441"
  },
  {
    "caption": "B. BiFC assays to show in vivo protein interactions. Epidermal cells of N. benthamiana leaves were co-transformated with cCFP-CO and nYFP-CIB1, with cCFP-CO and nYFP, or with cCFP and nYFP-CIB1. BF, bright field. Merge, overlay of the YFP and bright field images. Scale bars: 50 μm. Data information: For each experiment, two or more biological replicates were performed.",
    "ncbi_link": "cCFP: 
nYFP: 
CIB1: 829604
CO: 831441"
  },
  {
    "caption": "C. Split-LUC assay showing that CIB1 interacts with CO. Leaf epidermal cells of N. benthamiana were co-transformed with CO-nLUC and cLUC-CIB1 or cLUC or nLUC with cLUC-CIB or cLUC. Data information: For each experiment, two or more biological replicates were performed.",
    "ncbi_link": "cLUC: 
nLUC: 
CIB: 829604
CIB1: 829604
CO: 831441"
  },
  {
    "caption": "D. Co-IP assays of samples prepared from 10-day-old 35S:Myc-CIB1, 35S:CO-Flag or 35S:Myc-CIB1/35S:CO-Flag seedlings grown in LDs. Data information: For each experiment, two or more biological replicates were performed.",
    "ncbi_link": "Flag: 
Myc: 
CIB1: 829604
CO: 831441"
  },
  {
    "caption": "E. qPCR results showing mRNA expression of FT in the genotypes indicated. The transcript levels in Col are set to 1.0. Samples were collected from 7-day-old seedlings of the genotypes indicated at ZT16. Data information: error bars indicate standard error within three biological replicates and for each of these two technical replicates were performed.",
    "ncbi_link": "FT: 842859"
  },
  {
    "caption": "G. Box plots (the minimum, first quartile, median, third quartile, and maximum are shown, with data >1.5 interquartile ranges denoted with circles) for relative reporter activity (LUC/REN) in plants expressing different reportors and effectors. The relative LUC activities normalized to the REN activity are shown. The LUC/REN in plants expressing ProFT alone is set to 1.0. Data information: data are presented as mean ± SD, n=4. The letters "a" to "g" indicate statistically significant differences determined by Tukey's HSD test (P≤0.05). Two biological replicates were performed.",
    "ncbi_link": "LUC: 
REN: 
FT: 842859"
  },
  {
    "caption": "B. Co-IP assays showing that CRY2, CIB1 and CO form a protein complex. Samples were prepared from 10-day-old WT or 35S:Myc-CIB1/35S:CO-Flag or 35S:Myc-CIB1/35S:CO-Flag /cry2-1 seedlings grown in LDs (16L/8D), and samples were collected at ZT16.",
    "ncbi_link": "Flag: 
Myc: 
CIB1: 829604
CO: 831441
cry2: 839529"
  },
  {
    "caption": "C. Co-IP assays of samples prepared from 10-day-old 35S:Myc-CIB1/35S:CO-Flag 35S:Myc-CIB1/35S:CO-Flag /cry2-1 seedlings grown in LDs (16L/8D). Samples were collected at the times indicated over the course of one day.",
    "ncbi_link": "Flag: 
Myc: 
CIB1: 829604
CO: 831441
cry2: 839529"
  },
  {
    "caption": "E. Representative results of the ChIP-qPCR assays. Chromatin fragments (~500 bp) were prepared from 10-day-old 35S:Myc-CIB1/35S:CO-Flag seedlings, immunoprecipitated by the anti-CRY2, anti-Flag (CO-Flag) , anti-Myc (Myc-CIB1) antibody or anti-preimmune IgG, and the precipitated DNA was analyzed by qPCR using the primer pairs indicated. The IP/input ratio of anti-preimmune is set to 1.0. Data information: the relative IP/input ratios are shown with their standard deviation (n = 3). Two biological replicates were performed.",
    "ncbi_link": "Flag: 
Myc: 
CIB1: 829604
CO: 831441"
  },
  {
    "caption": "F. Box plots (the minimum, first quartile, median, third quartile, and maximum are shown, with data >1.5 interquartile ranges denoted with circles) for relative reporter activity (LUC/REN) in plants expressing different reportors and effectors. The LUC/REN in plants expressing ProFT alone is set to 1.0. Immunoblots were done to show GFP-CRY2W374A, Myc-CIB1 and Myc-CO protein levels in the transient Dual-LUC assay. Samples were separated on 10% SDS-PAGE, blotted, probed with the anti-Myc antibody, and with the anti-GFP antibody. Data information: the relative LUC activities normalized to the REN activity are shown (LUC/REN) with their standard deviation (n =6). The letters "a" to "f" indicate statistically significant differences determined by Tukey's HSD test (P≤0.05). Two biological replicates were performed.",
    "ncbi_link": "LUC: 
REN: 
FT: 842859"
  },
  {
    "caption": "(C,D) De‐activation of autophagy returns DOR to the nucleus. HeLa cells were transiently transfected with DOR and incubated for 1 h with DMEM (basal) or HBSS (starvation). Cells were then incubated with normal DMEM for an additional hour (starvation+GM). The intracellular distribution of DOR was determined by immunofluorescence. DOR is shown in red and the nuclei are in blue. Scale bars, 5 μm. Cell lysates were also obtained and western blot assays were performed with specific antibodies. 3MA, 3‐methyladenine; DAPI, 4′,6‐diamidino‐2‐phenylindole; DMEM, Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; HBSS, Hank's balanced salt solution; LC3, microtubule‐associated protein 1A/1B‐light chain 3.",
    "ncbi_link": "DOR: 58476"
  },
  {
    "caption": "DOR localizes to autophagosomes when autophagy is activated. (A) Confocal images of HeLa cells transiently transfected with DOR and GFP‐LC3, and incubated for 1h with DMEM, HBSS (starvation), 2 μM rapamycin or HBSS containing 50 μM chloroquine. Nuclei were labelled with DAPI. Scale bars, 10 μm.",
    "ncbi_link": "DOR: 58476"
  },
  {
    "caption": "(D) Confocal images of HeLa cells transiently transfected with DOR and LAMP1‐GFP, or with YFP‐LC3 and LAMP1‐GFP. Scale bars, 10 μm. Contrast‐corrected merge RGB pictures and the Z‐projection of Product of the differences from the mean (PDM) images are shown in all panels. Colour scales of PDM images have different maximal values, so the different conditions are not comparable from these projections. Product of the differences from the mean (PDM) values closer to 1 show reliable colocalized pixels. DAPI, 4′,6‐diamidino‐2‐phenylindole; DMEM, Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; GFP, green fluorescent protein; HBSS, Hank's balanced salt solution; LAMP1, lysosomal‐associated membrane protein 1; LC3, microtubule‐associated protein 1A/1B‐light chain 3.",
    "ncbi_link": "DOR: 58476"
  },
  {
    "caption": "(A) DOR gain‐of‐function accelerates the degradation of proteins of middle-long half‐life. Untreated HeLa cells and those transiently transfected with DOR were incubated in DMEM or HBSS. *Significant effects of starvation, P0.01; τsignificant effects caused by DOR overexpression, P0.01.",
    "ncbi_link": "DOR: 58476"
  },
  {
    "caption": "(B) DOR overexpression enhances autophagosomal formation. LC3‐GFP‐positive vacuoles were counted in 100 transfected HeLa cells (with GFP‐LC3 and TRα1, or GFP‐LC3 and DOR). *Significant effects of starvation, P0.001; τsignificant effects of DOR overexpression, P0.001.",
    "ncbi_link": "TRα1: 100702192
LC3: 440738///81631///84557
DOR: 58476"
  },
  {
    "caption": "(C,D) HeLa cells transiently transfected with empty pCDNA3 or DOR were incubated in DMEM (basal) or in HBSS (starvation). Cells were processed by transmission electron microscopy. Arrows indicate autophagosomes. Insets are autophagosomes (diameter, 407±63 nm). Scale bars, 1 μm. Autophagosomes were counted in 50 randomly chosen transfected cells. *Significant effects of starvation, P0.05; τsignificant effects of DOR overexpression, P0.05. DMEM; Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; GFP, green fluorescent protein; HBSS; Hank's balanced salt solution; LC3, microtubule‐associated protein 1A/1B‐light chain 3.",
    "ncbi_link": "DOR: 58476"
  },
  {
    "caption": "(A,B) C2C12 myoblasts were previously infected with lentiviruses encoding scrambled RNA, DOR siRNA1 or DOR siRNA2. Endogenous LC3 was detected by immunofluorescence. LC3‐positive puncta were counted in 100 cells per group under basal conditions or starved for 20 min. Scale bars, 10 μm. *Significant effects of starvation, P0.001; τsignificant effects caused by DOR knockdown, P0.001.",
    "ncbi_link": "DOR: 68728"
  },
  {
    "caption": "(C,D) Scramble or DOR siRNA1 C2C12 cells were processed by transmission electron microscopy. Arrows indicate autophagosomes. Insets are autophagosomes. Scale bars, 1 μm. Autophagosomes were counted in 50 randomly chosen cells. *Significant effects of DOR repression, P0.001.",
    "ncbi_link": "DOR: 68728"
  },
  {
    "caption": "(E) Scramble or DOR siRNA1 C2C12 cells were incubated in DMEM with and without 10 mM 3MA. *Significant effects of DOR knockdown, P0.01; τsignificant effects caused by 3MA, P0.01. 3MA, 3‐methyladenine; DMEM, Dulbecco's modified Eagle medium; DOR, diabetes‐ and obesity‐regulated gene; LC3, microtubule‐associated protein 1A/1B‐light chain 3.",
    "ncbi_link": "DOR: 68728"
  },
  {
    "caption": "(A) Decrease of mRNA levels in TubG4, UAS‐CG11347‐RNAi animals compared with TubG4 controls. All measurements were normalized to rp49. *Significant change, P0.05.",
    "ncbi_link": "rp49: 
Tub: 
CG11347: 38543"
  },
  {
    "caption": "(B) Lysotracker staining of fat bodies. No Lysotracker staining is observed in feeding early third‐instar larvae, whereas Lysotracker‐positive granules (red) accumulate in fat body cells of wandering late third‐instar controls (upper panels, TubG4/+). dDOR knockdown animals (TubG4, UAS‐CG11347‐RNAi T4, lower panels) show decreased staining of Lysotracker‐positive granules in wandering late third‐instar larvae. Nuclei are shown in blue. Scale bars, 50 μm. (C) The number of Lysotracker‐positive puncta per unit area are shown for each genotype (control and RNAi), normalized to the value for control cells processed in parallel. *Significant change, P0.05.",
    "ncbi_link": "Tub: 
CG11347: 38543
dDOR: 38543"
  },
  {
    "caption": "(D) Transmission electron microscopy images of fat body cells from wandering late third‐instar larvae. Developmental autophagy results in the accumulation of large autolysosomes (AL) in control (TubG4/+) larvae, whereas only a few autolysosomes are seen in CG11347 RNAi fat body cells of the same age. Control and RNAi fat bodies present lipid droplets (LP) with a 'striped' appearance, which is an electron microscopy artefact. Scale bars, 5 nm. dDor, CG11347, a homologue of DOR; DOR, diabetes‐ and obesity‐regulated gene; mRNA, messenger RNA; wt, wild type.",
    "ncbi_link": "Tub: 
CG11347: 38543
DOR: 38543"
  },
  {
    "caption": "(A) Optically evoked auditory brainstem response in an AAV-CatCh-injected gerbil in response to a 1 ms laser pulse of ~35 mW (mean of 1000 stimulus presentations at 10 Hz repetition rate).",
    "ncbi_link": "CatCh: "
  },
  {
    "caption": " (B-D) Catch-eYFP-expressing SGNs in the apical cochlear turn identified by parvalbumin expression (B) and CatCh-eYFP (C). The inlay (D´) of the merged immunostaining (D) indicates the lack of CatCh-EYFP signal in inner hair cells (dashed white line). Scale bar: 20 µm. ",
    "ncbi_link": "Catch: 
eYFP: "
  },
  {
    "caption": " (A-D) Exemplar STCs in response to SGN illumination with a single μLED (A), a block of four neighboring μLEDs (B) and all μLEDs of an oCI inserted via the round window in a CatCh-transduced gerbil (C) and with all µLEDs in a wildtype gerbil (WT; D). μLEDs were spaced by 250 μm. ",
    "ncbi_link": "CatCh: "
  },
  {
    "caption": " (G-H) Exemplar STCs in response to SGN illumination with all µLEDs in a CatCh-transduced, kanamycin-deafened gerbil before (G) and after (H) sacrifice. ",
    "ncbi_link": "CatCh: "
  },
  {
    "caption": " (I) Maximum strength of ICC responses (mean ± standard deviation) evoked by oCI stimulation with 1 (indiv.; n = 129/77 µLEDs in N = 9/3 hearing/deaf gerbils), 4 (block; n = 62/27 blocks in N = 9/3 hearing/deaf gerbils), and 16 (all; n = 24/9 oCIs in N = 9/3 hearing/deaf gerbils) active µLEDs, and with a laser-coupled optical fiber (~35 mW; n = 9/3 fiber stimulations in N = 9/3 hearing/deaf gerbils) in CatCh-transduced gerbils (One-way ANOVA (F-value: 73.25, 4 degrees of freedom, p = 5.19*10-45) and post-hoc multiple comparison test; indiv. vs. block: p = 9.9*10-9; block vs. all: p = 0.0096; all vs. fiber: p = 0.0016; all CatCh vs. all WT: p = 9.9*10-9;**: p < 0.01, ***: p < 0.001, n.s. = non-significant). oCI stimulation with all µLEDs has also been performed in WT animals (n = 7/7 oCIs, N = 2/2 hearing/deaf gerbils) and in sacrificed CatCh-transduced animals (post-mortem; n = 5/1 oCIs in N = 5/1 hearing/deaf gerbils). Brown dots indicate data recorded from deafened animals. (J) Number of active electrodes (d´ > 1; mean ± standard deviation) upon oCI stimulation with 1 (n = 129/77 µLEDs in N = 9/3 hearing/deaf gerbils), 4 (n = 62/27 blocks in N = 9/3 hearing/deaf gerbils), and 16 µLEDs (n = 24/9 oCIs in N = 9/3 hearing/deaf gerbils), and with optical fiber stimulation (n = 9/3 fiber stimulations in N = 9/3 hearing/deaf gerbils) in CatCh-transduced gerbils (One-way ANOVA (F-value: 30.18, 4 degrees of freedom, p = 1.42*10-21) and post-hoc multiple comparison test; indiv. vs. block: p = 6.8*10-5; block vs. all: p = 0.006; all vs. fiber: p = 0.25; all CatCh vs. all WT: p = 9.9*10-9;**: p < 0.01, ***: p < 0.001, n.s. = non-significant). Responses to oCI stimulation with all µLEDs were also observed in hearing WT animals (n = 3 oCIs in 2 gerbils). No active electrodes were found in response to 4/7 oCI stimulations in 2/2 hearing/deaf wildtype gerbils). (K) Thresholds (d´ = 1, measured at the best electrode (BE)) for ICC activation evoked with 16 active µLEDs on an oCI (n = 24/9 in N = 9/3 hearing/deaf gerbils) and with a laser-coupled optical fiber (n = 9/3 in N = 9/3 hearing/deaf gerbils; p = 0.012, Wilcoxon rank sum test). Central horizontal line indicates the median, lower, upper horizontal lines indicate the minimum and maximum values, and box edges indicate the 25th and 75th percentile, respectively. ",
    "ncbi_link": "CatCh: "
  },
  {
    "caption": "(B) Immunoblot analysis of the immunoprecipitated HA-SOX9 or FLAG- FBW7α and their pull-down products. The corresponding Western blotting from the whole cell extract (WCE) of the transfected HEK293 showed the levels of exogenous HA-SOX9 or FLAG-FBW7α proteins in the total input. Cells were treated with 10 µM MG132 for 4 hours prior to harvesting for the immunoprecipitation. Blots are representative from 3 independent experiments.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(C) FBW7α immunoblot eluted from the agarose bead-bound peptide, which had been incubated with the recombinant SCF-FBW7α for 1 hour at 37◦C. The agarose bead-bound peptide contains either the non-phosphorylated SOX9 amino acid sequence spanning from residue number 231 to 245 (SOX9 peptide), or those with the threonine corresponding to residue number 236 and 240 being phosphorylated (pSOX9 peptide). The input (10%) showed the level of the supplemented recombinant SCF-FBW7α in the in vitro binding reaction. Shown blot is representative from 2 independent experiments.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(D) Representative Western blotting set from 3 independent repeats of pT236-SOX9 from lysates of HEK293 transfected with either HA-EV or HA-SOX9. Each lysate were immediately divided and left untreated or subjected to lambda phosphatase (λ-PPase) treatment for 1 hour at 37◦C prior to gel electrophoresis. SOX9 blot showed the presence of SOX9 protein in both the untreated and the phosphatase-treated SOX9-transfected cell lysates.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(E) Bead-immobilized in vitro translated (IVT) HA-SOX9 wild type (WT) or T236/240 mutant were either untreated or subjected to in vitro GSK3 kinase reaction for 90 minutes at 37◦C prior to elution and gel electrophoresis. The SOX9 blot showed total SOX9 protein eluted from the beads from each reaction. Shown immunoblots are single representative experiment from 3 independent repeats.",
    "ncbi_link": "GSK3: 2932///2931
SOX9: 20682"
  },
  {
    "caption": "(F) GSK3-mediated phosphorylation of threonine 236 promoted SOX9 interaction with recombinant SCF-FBW7α in vitro. Bead-immobilized IVT HA-SOX9 were either untreated or phosphorylated with GSK3 as described in (E) prior to further incubation with recombinant SCF-FBW7α for in vitro binding assay. Immunoblot showed FBW7α protein in the in vitro binding reaction (input) as well as those which had been eluted from the untreated and GSK3-treated immobilized SOX9. The set of blots shown is representative from 3 independent experiments.",
    "ncbi_link": "GSK3: 2932///2931"
  },
  {
    "caption": "(A) Endogenous SOX9 protein turnover in the presence of cycloheximide following RNAi depletion of FBW7α, β or γ. HEK293 cells were transfected with 20 nM of non-targeting scramble RNA or those specifically targeting FBW7α, β or γ for 72 hours prior to chase with addition of 100 ng /mL cycloheximide. Immunoblot of Cyclin E, an established SCF-FBW7 substrate, was used to assess the efficacy of RNAi-mediated depletion of FBW7 protein with GAPDH served as protein loading control.",
    "ncbi_link": "FBW7α: 55294"
  },
  {
    "caption": "(D) Expression of FLAG-FBW7α enhanced HA-SOX9-WT protein turnover, which can be attenuated with addition of 10 µM MG-132 (MG) in HEK293 cells. By contrast, forced expression of FLAG-FBW7α did not enhance HA-SOX9-T236A and -T236A/T240A protein turnover over the course of 4 hours protein chase. Protein loading for each sample was indicated by the level of β-actin protein. The set of blots shown is representative from 4 independent experiments.",
    "ncbi_link": "FBW7α: 55294
SOX9: 20682"
  },
  {
    "caption": "(F) The RNAi depletion of GSK3ß decreased FBW7α-induced HA-SOX9-WT turnover in HEK293 cells. The HA-SOX9-WT protein turnover was examined in the presence of 100 ng/mL cycloheximide, 48 hours following si-GSK3ß (20 nM) transfection, 24 hours after co-expression of HA-SOX9-WT and FLAG-FBW7α. Immunoblots of GSK3ß demonstrated depletion of GSK3ß protein with the siRNA. Changes in SOX9 protein level in the representative blots were analysed relative to GAPDH using ImageJ. The set of blots shown is representative from 3 independent experiments.",
    "ncbi_link": "FBW7α: 55294
GSK3ß: 2932
SOX9: 20682"
  },
  {
    "caption": "(G) Forced FLAG-FBW7α-WT expression promoted poly-ubiquitylation of endogenous SOX9 in HEK293, which accumulated further in the presence of 10 µM MG132. Expression of non-functional FBW7α lacking the F-box domain (ΔF), or those containing R465A mutation did not induce SOX9 poly-ubiquitylation in vivo. Ubiquitylation assay was performed under denaturing condition to disrupt non-covalently linked ubiquitin as described in the Materials & Methods. Expression of various FLAG-FBW7α constructs and endogenous SOX9 protein were examined in the whole cell extract (WCE). GAPDH protein was used to indicate total protein loading with protein loading. The set of blots shown is representative from 4 independent experiments.",
    "ncbi_link": "FBW7α: 55294"
  },
  {
    "caption": "(H) Reconstitution of SOX9 ubiquitylation reaction by FLAG-FBW7α in vitro. Immobilized-IVT HA-SOX9 WT were incubated with complete ubiquitylation reaction mixture containing either the eluted FLAG-FBW7α-WT or the ΔF mutant for 60 minutes at 37◦C. Reaction mixture lacking the UbE1, an E1 ubiquitin-activating enzyme, or UbcH3, an E2 ubiquiting-conjugating enzyme, served as negative control for the reaction. SOX9 ubiquitylation was assessed following elution of the protein from the immobilized beads under denaturing condition as described in Materials & Methods. The set of blots shown is representative from 3 independent experiments.",
    "ncbi_link": "FBW7α: 55294"
  },
  {
    "caption": "(B) Immunoblotting of HA-SOX9-WT protein following expression of various FLAG-FBW7α constructs including wild type (WT), or those with R465A or R479A mutation in Daoy. The cells were transfected with equal amount of HA-SOX9-WT and FLAG-FBW7α and the whole cell lysates were collected 24 hours following the transfection. GAPDH proteins were shown to indicate total protein loading for each sample. The set of blots shown is representative from 2 independent experiments.",
    "ncbi_link": "FBW7α: 55294"
  },
  {
    "caption": "(C) Co-immunoprecipitation of HA-SOX9 with either wild type (WT) or R465A- FLAG-FBW7α. Unlike the wild type protein, FLAG-FBW7α containing arginine 465 mutation did not significantly co-immunoprecipitate with HA-SOX9 (IP with anti HA antibody) and vice versa (IP with anti FLAG antibody). The expressions of HA-SOX9 and FLAG- FBW7α- WT or R465A mutant were assessed in the whole cell extract (WCE) of the transfected HEK293 with GAPDH protein used to indicate total protein loading.",
    "ncbi_link": "FBW7α: 55294"
  },
  {
    "caption": "(D) Comparison of FBW7 mRNA expression across the medulloblastoma subgroups (WNT, SHH, Group 3, and 4) in a cohort containing 423 medulloblastoma cases. Expression of FBW7 in both normal fetal (n= 5) and adult cerebellum (n = 13) were used for comparison against the medulloblastoma.",
    "ncbi_link": "FBW7: 55294"
  },
  {
    "caption": "(E) Overall survival analysis of medulloblastoma patient based upon FBW7 expression level. Analysis was performed on 383 out of the 423 cases from which the survival data were available. Cohort was divided into high- (blue line) and low- FBW7 (red line) expressing subgroup using FBW7 median expression as group classifier. Statistical analysis was determined by using a LogRank test.",
    "ncbi_link": "FBW7: 55294"
  },
  {
    "caption": "(F) Correlation analysis between SOX9 protein/mRNA and FBW7 mRNA expression level from medulloblastoma tissue microarray consisting of 142 tissue samples. SOX9 protein level was scored following immunohistochemistry staining, while SOX9 and FBW7 mRNAs expression by the RNA Scope as described in Materials & Methods. A modest negative correlation was determined by Kendall's correlation test (τ = - 0.223, p<0.001) between SOX9 protein/mRNA and FBW7 expression. Affiliation of samples with medulloblastoma subgroups was indicated by different colored circle (blue=WNT, red=SHH, yellow=Group 3, green=Group 4, grey=Undetermined).",
    "ncbi_link": "FBW7: 55294
SOX9: 6662"
  },
  {
    "caption": "(A) Overall survival analysis of mice bearing Daoy cell line expressing SOX9 with doxycycline (dox) -inducible FBW7α ( Daoy-SOX9/T-FBW7α). The dox-preconditioned or the control cells (105cells) were orthotopically xenografted to the cerebellum of 6-weeks old Athymic Nude-Foxn1nu mice, which were continuously fed with either the dox-containing chow (red line) or the regular chow food (green line), respectively. Micexenografted with dox-preconditioned Daoy-SOX9/T-FBW7α and fed continuously with dox-containing chow (red line) survived longer (p= 0.0285) than the control group (green line)",
    "ncbi_link": "FBW7α: 55294
Foxn1: 15218
SOX9: 20682"
  },
  {
    "caption": "(B) Representative of Haemotoxylin & Eosin (H&E) staining of medulloblastoma tumors arising from the orthotopic xenograft experiment described in (A). Both the control (no dox-treated) and the dox-treated mice developed primary intracerebellar tumors (green and red arrows, respectively). SOX9-expressing Daoy tumors disseminated to the spinal cord (3/4; green asterisks), while the group continuously receiving dox-containing chow showed no metastatic spread (0/4).",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(C) Representative bright field images of migrating Daoy-SOX9/T-FBW7α in the absence or presence of Dox. Daoy-SOX9/T-FBW7α cells were either maintain in regular culture or pre-conditioned with dox prior to experiments. The cells (2 x 105cells / insert) were seeded and let to migrate across 5 μm filter pore toward the laminin-coated trans-well for 4 hours prior to fixation and staining with crystal violet. Histogram quantification of cell migration were performed by measuring the crystal violet absorbance of the stained-migrating cells and presented as mean + standard deviation from 2 independent experiments each containing 2 technical replicates.",
    "ncbi_link": "FBW7α: 55294
SOX9: 20682"
  },
  {
    "caption": "(D) Representative H&E staining of primary (arrow) and disseminated tumors (asterisk) arising from orthotopic xenograft of parental and SOX9-expressing medulloblastoma initiating cells (MIC and MIC-Sox9, respectively). Quantification of primary and metastatic tumors arising from both of MIC (n=16) and MIC-SOX9 (n=8) is shown in the histogram (p=0.0000136).",
    "ncbi_link": "SOX9: 20682
Sox9: 20682"
  },
  {
    "caption": "(E) Quantitative comparison of MIC and MIC-SOX9 cells to migrate across 5 μm filter pore toward the laminin-coated trans-well for 4 hours. Quantification of cell migration were performed as described in (C) and presented as mean + standard error mean from 6 replicates.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(F) Transwell migration of SOX9-expressing MIC with dox-inducible FBW7α or dominant negative ∆F FBW7α. The cells were either maintain in regular culture or pre-conditioned with dox prior to assessment of in vitro transwell migration as described in (C). Data are mean + standard deviation from 2 independent experiments each containing 2 technical replicates.",
    "ncbi_link": "FBW7α: 55294
SOX9: 20682"
  },
  {
    "caption": "(A) Scatter plot depicting the relationship between transcriptional changes measured as log2 FC between EV to SOX9-WT (x-axis) and EV to SOX9-T236/T240A (y-axis). Each dot represents one transcript, with colored dots indicating transcripts upregulated (log2 FC>0.585; p<0.05; red dots) or downregulated (log2 FC<-0.585; p<0.05; blue dots) in both comparisons. The transcript corresponding to the SOX9 gene is highlighted as a red filled dot. Indicated r-value indicates Spearman's rank correlation coefficient between the two FC profiles.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(B) Box-and-Whisker plot displaying the sample specific expression of three FBW7 isoforms; FBW7α (NM_033632), FBW7β (NM_018315) and FBW7γ(NM_001013415'). Each box represents the expression distribution over three replicates.",
    "ncbi_link": "FBW7α: 55294
FBW7β: 55294
FBW7γ: 55294"
  },
  {
    "caption": "(D) Heat map of the row-wise z-scores of 16 EMT hallmark genes in SOX9-WT and -T236/T240A samples. Heat map was generated using the GenePattern software (Reich et al., 2006).",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(E) Quantitative PCR (qPCR) of SNAI2 (SLUG), VIM and POU3F1 (OCT6) (normalized to GAPDH levels) in MB002 cells stably transduced with EV (set to 1), SOX9-WT and SOX9-T236/240A. Cells were induced for 8 or 24 hours with doxycycline.",
    "ncbi_link": "GAPDH: 
OCT6: 5453
POU3F1: 5453
SLUG: 6591
SNAI2: 6591
SOX9: 20682
VIM: 7431"
  },
  {
    "caption": "(F) Western blot of SOX9, HA-SOX9, pSOX9-T236, SNAI2 (SLUG), VIM and POU3F1 (OCT6) in MB002 cells stably transduced with EV, SOX9-WT and SOX9-T236/240A. Cells were induced for 24 and 48 hours with doxycycline and GAPDH were used as a loading control.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(G) Heat map of the row-wise z-scores of 14 pro-metastasis genes differentially expressed between SOX9-WT and -T236/T240A samples and previously identified as SOX9 target genes (Kadaja et al., 2014, Larsimont et al., 2015, Oh et al., 2014). Heat map was generated using the GenePattern software (Reich et al., 2006).",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(A) Cisplatin dose response curves of (i) MB002, (ii) Daoy, and (iii) MIC in the absence (EV) or presence of SOX9 by Alamar blue. Cells were pre-conditioned with doxycycline to induce expression of SOX9 (or EV) prior to treatment with increasing concentrations of cisplatin. The IC50 were calculated following 5 (MB002 and MIC) or 3 days (Daoy) of treatment. Data are mean + standard deviation from 3 independent repeats, each containing 5 technical replicates.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(B) Cisplatin dose response curves of SOX9-expressing (i) Daoy and (ii) MIC in the absence or presence of FBW7α. Experiments and data analysis were performed as described in (A)",
    "ncbi_link": "FBW7α: 55294
SOX9: 20682"
  },
  {
    "caption": "(C) Overall survival analysis of mice bearing Daoy or Daoy-expressing dox-inducible SOX9 treated with cisplatin. The dox-preconditioned cells (105 cells) were orthotopically xenografted to Nude-Foxn1nu mice and left for 1 week to prior to being treated with vehicle control or cisplatin (2mg/kg) intraperitoneally for every other day for a total of 6 doses.",
    "ncbi_link": "Foxn1: 15218
SOX9: 20682"
  },
  {
    "caption": "(D) Heat map of the row-wise z-scores of 11 genes associated with cisplatin resistance in MB002 expressing Sox9-WT or Sox9-T236/T240A. Heat map was generated using the GenePattern software.",
    "ncbi_link": "Sox9: 20682"
  },
  {
    "caption": "(E) Quantitative analysis of ATP7A, DUSP2, and TTK mRNAs in MB002 following expression of SOX9-WT or SOX9-T236/240A. Total RNA were collected 24 hours following doxycycline treatment, from which cDNA were generated for qPCR. Data are mean mRNA level (normalized to B2M transcript) + standard deviation from 3 independent experiments with statistical significance were determined by Multiple comparisons 2-way ANOVA with Bonferroni's post-test.",
    "ncbi_link": "B2M: 
ATP7A: 538
DUSP2: 1844
SOX9: 20682
TTK: 7272"
  },
  {
    "caption": "(F) Time course western blotting of HA-SOX9, ATP7A, DUSP2, ERK1/2 pThr202/Tyr204 and total ERK1/2 in MB002 cells following doxycycline induction of either EV, SOX9-WT or SOX9-T236/240A. GAPDH was used as a loading control.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(B) Western blotting of endogenous SOX9 protein turnover in the presence of PI3K/mTOR dual inhibitor, AZD2014. Daoy were transfected with either siScr or siFBW7 for 48 hours prior to further treatment with 1 µM AZD2014. The cycloheximide chase of SOX9 protein turnover was examined 2 hours following the inhibitor treatment. Immunobloting of Cyclin E protein was used to indicate the efficacy of siFBW7 transfection. Changes in SOX9 protein level in the representative blots were analysed relative to GAPDH using ImageJ. The set of blots shown is representative from 3 independent experiments.",
    "ncbi_link": "FBW7: 55294"
  },
  {
    "caption": "(E) Western blotting profiling of MB002 expressing EV, SOX9-WT, or SOX9-T236/240A following 48 hours treatment with cisplatin, AZD2014, and their combination. The set of blots shown is representative from 3 independent experiments.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(F) Quantification of cell viability of MB002 expressing EV, SOX9-WT, or SOX9-T236/240A following 5 days treatment with either of 10 μM cisplatin (black bars), 0.5 µM AZD2014 (blue bars), or their combination (red bars). Data are mean + standard deviation from 3 independent experiments, from which statistical significance were analysed by 2-way ANOVA multiple comparisons with Bonferroni's post-test.",
    "ncbi_link": "SOX9: 20682"
  },
  {
    "caption": "(G) Immunoblots of ATP7A and DUSP2 protein following doxycycline treatment of Daoy-SOX9/T-FBW7α. The cells were either untreated or incubated with 5 µg/mL doxycycline for 72 hours prior to being harvested for gel electrophoresis. The set of blots shown is representative from 2 independent experiments.",
    "ncbi_link": "FBW7α: 55294
SOX9: 20682"
  },
  {
    "caption": "NIX and BNIP3 are required for mitophagy induced by MLN4924 and other HIF1α stabilisers. Parental HeLa cells and NIX/BNIP3 double knockout (NIX/BNIP3 DKO) HeLa cells expressing mt-Keima were treated with DFP (1 mM), MLN4924 (0.5 μM), or DMOG (10 nM) for 24 hours and analysed by live-cell confocal microscopy. The emission signals obtained after excitation with the 458 nm laser (neutral pH) or 561 nm laser (acidic pH) are shown in green and magenta, respectively. Quantification of mitophagy shown in panel A. Mitophagy is represented as the ratio of mt-Keima 561 nm fluorescence intensity to mt-Keima 458 nm fluorescence intensity for individual cells normalised to the mean of the untreated condition. In B , the measurements from individual cells are represented as translucent grey dots, and the mean ratio from each independent experiment is represented by coloured circles. The centre lines and bars depict the mean of the averaged independent replicates +/- standard deviation. N=4. A minimum of 50 cells were analysed for each condition within each individual replicate experiment, and over 300 cells were analysed for each condition in total. P values were calculated based on the mean ratio values from independent experiments using one-way ANOVA (*P<0.05, **P<0.005, ***P<0.001, ****P<0.0001).",
    "ncbi_link": "mt-Keima: 
BNIP3: 664
NIX: 665"
  },
  {
    "caption": "Analysis of NIX and BNIP3 protein levels after MLN4924, DMOG, or DFP treatments. HeLa cells or HeLa NIX/BNIP3 DKO cells were treated with MLN4924, DMOG, or DFP for 24 hours. Total-cell lysates corresponding to conditions in panel A were subject to immunoblotting.",
    "ncbi_link": "BNIP3: 664
NIX: 665"
  },
  {
    "caption": "Inhibition of HIF1α with echinomycin prevents DFP-induced mitophagy but not MLN4924-induced mitophagy. U2OS cells expressing mt-Keima were treated with the indicated drugs for 24 hours and analysed by live-cell confocal microscopy. Quantification of mitophagy shown in panel D. In F, the measurements from individual cells are represented as translucent grey dots, and the mean ratio from each independent experiment is represented by coloured circles. The centre lines and bars depict the mean of the averaged independent replicates +/- standard deviation. N=4. A minimum of 50 cells were analysed for each condition within each individual replicate experiment, and over 300 cells were analysed for each condition in total. P values were calculated based on the mean ratio values from independent experiments using one-way ANOVA (*P<0.05, **P<0.005, ***P<0.001, ****P<0.0001).",
    "ncbi_link": "mt-Keima: "
  },
  {
    "caption": "Re-expression of FBXL4 into FBXL4-defective CRISPR lines reduces the levels of NIX and BNIP3 in FBLX4 deficient clones. FBXL4-deficient 2G10 and FBXL4-deficient 1D4 cell lines were stably transduced with a doxycycline-inducible FBXL4-HA construct. Cells were treated with doxycycline for the indicated times prior to immunoblotting with the specified antibodies.",
    "ncbi_link": "CRISPR: 
HA: 
FBLX4: 26235
FBXL4: 26235"
  },
  {
    "caption": "FBXL4 localises to the mitochondrial outer membrane. Cells transiently transfected with FBXL4-HA-C were treated with DFP for 24 h. Cells were stained with an anti-HA antibody (to recognise FBXL4) and either TOM20 (an outer mitochondrial membrane protein) or TIM50 (an inner mitochondrial membrane protein). The line scan intensity profiles for FBXL4 (green) and TOM20/TIM50 (magenta) represent fluorescence intensity (y-axis) plotted against distance (x-axis). Scale bars = 5 μm.",
    "ncbi_link": "HA: 
FBXL4: 26235"
  },
  {
    "caption": "FBXL4 is a proximity interactor of NIX and BNIP3. Cells expressing inducible BirA-BNIP3, BirA-NIX and BirA control were transduced with a lentiviral vector expressing FBXL4, as indicated. Cells were treated with doxycycline for 48 hours (to induce BirA-bait protein expression), biotin for 24 hours (for the biotinylation reaction), and, where indicated, MLN4924 for 24 hours (to stabilise NIX and BNIP3). Streptavidin-coupled beads were used to capture the biotinylated proteins. FBXL4 was specifically detected in the eluate from BirA-BNIP3 and BirA-NIX compared with BirA-alone.",
    "ncbi_link": "BirA: 948469
BNIP3: 664
NIX: 665
FBXL4: 26235"
  },
  {
    "caption": "NIX and BNIP3 polyubiquitylation depends on FBXL4. U2OS or U2OS-FBXL4 KO cells were co-transfected with TR-TUBE and either myc-BNIP3 or myc-NIX, as indicated. Cell lysates obtained 48 hours post-transfection were immunoprecipitated with anti-FLAG beads, and the immunoprecipitates were analysed by immunoblotting using anti-myc antibody (to detect ubiquitylated NIX or BNIP3). The line on the right marks a ladder of bands corresponding to polyubiquitylated myc-BNIP3 or myc-NIX",
    "ncbi_link": "myc: 
BNIP3: 664
NIX: 665
FBXL4: 26235"
  },
  {
    "caption": "Loss of FBXL4 leads to an increase in mitophagy, which can be reduced by re-expression of FBXL4. U2OS mt-Keima FBXL4 KO clones (2G10 and 1D4) expressing doxycycline-inducible wild-type FBXL4-HA were treated with doxycycline for 72 hours. The emission signals obtained after excitation with the 458 nm laser (neutral pH) or 561 nm laser (acidic pH) are shown in green and magenta, respectively.",
    "ncbi_link": "HA: 
mt-Keima: 
FBXL4: 26235"
  },
  {
    "caption": "Depleting NIX/BNIP3 via siRNA reduces the increased mitophagy caused by FBXL4 deficiency. U2OS mt-Keima cells and U2OS mt-Keima FBXL4 KO 2G10 cells were transfected with siRNAs targeting both NIX and BNIP3 (NIX/BNIP3 si) or non-targeting siRNA (NT si). UT=untransfected.",
    "ncbi_link": "mt-Keima: 
BNIP3: 664
NIX: 665
FBXL4: 26235"
  },
  {
    "caption": "Corresponding cells from D-E were harvested for immunoblotting to analyse the extent of NIX and BNIP3 reduction after siRNA transfection.",
    "ncbi_link": "BNIP3: 664
NIX: 665"
  },
  {
    "caption": "Hyperstable NIX deletion mutants increase mitophagy compared with wild-type NIX. Hela Flp-in NIX KO mt-Keima cells stably expressing inducible NIX(WT), FLAG-NIX∆151-170, or FLAG-NIX∆171-184 were treated with doxycycline for 48 hours Mitophagy was visualised as in A and quantified as in B. Hyperstable BNIP3 deletion mutants increase mitophagy compared with wild-type NIX. Hela Flp-in NIX/BNIP3 DKO mt-Keima cells stably expressing BNIP3 deletion mutants were treated with doxycycline for 48 hours translucent grey dots represent measurements from individual cells. Coloured circles represent the mean ratio from independent experiments. The centre lines and bars represent the mean of the independent replicate means +/- standard deviation. N=3. At least 200 cells were analysed per condition. P values were calculated based on the mean values using a one-way ANOVA (*P<0.05, **P<0.005, ***P<0.001, ****P<0.0001). Scale bars = 20 μm.",
    "ncbi_link": "FLAG: 
mt-Keima: 
BNIP3: 664
NIX: 665"
  },
  {
    "caption": "FBXL4 patient-derived variants exhibit reduced efficiency compared to wild-type FBXL4 in mediating the downregulation and destabilization of NIX and BNIP3. U2OS FBXL4 KO (2G10) cells were rescued with constructs expressing wild-type FBXL4-HA, FBXL4(F-box mut), FBXL4(∆MTS), or specified patient variants. Cells were treated with cycloheximide for 3 hours prior to harvesting. Samples were lysed, and immunoblotting was performed. GFP serves as a marker of transduction efficiency/transgene expression. EV = empty vector.",
    "ncbi_link": "HA: 
FBXL4: 26235"
  },
  {
    "caption": "FBXL4-Arg482Trp and FBXL4-Gly568Ala patient variants are less efficient than FBXL4-wild-type at assembling into a complex with SKP1 and CUL1. FBXL4-KO cells expressing wild-type FBXL4-HA or FBXL4 variants were harvested and lysed. Whole-cell extracts were subjected to immunoprecipitation (IP) with anti-HA agarose beads and immunoblotting, as indicated.",
    "ncbi_link": "HA: 
FBXL4: 26235"
  },
  {
    "caption": "NIX/BNIP3 depletion mediated by siRNA reduces mitophagy in FBXL4-deficient patient fibroblast cells. FBXL4-deficient patient fibroblasts were transfected with siRNAs targeting both NIX and BNIP3 (NIX/BNIP3 si) or non-targeting siRNA (NT si) (left). Live-cell confocal microscopy was performed to visualise mitophagy and quantification was performed as in D (middle). The siRNA-mediated depletion of NIX and BNIP3 was evaluated by Western blotting (right). translucent grey dots represent measurements from individual cells. Coloured circles represent the mean ratio from independent experiments. The centre lines and bars represent the mean of the independent replicates +/- standard deviation. in H, N=3. Over 100 cells were analysed per condition. P values were calculated based on the mean values using a one-way ANOVA (*P<0.05, **P<0.005, ***P<0.001, ****P<0.0001). Scale bar = 20 μm.­ ",
    "ncbi_link": "BNIP3: 664
NIX: 665
FBXL4: 26235"
  },
  {
    "caption": "Ubiquitylation of endogenous NIX is restored upon expression of FBXL4 in patient-derived cells. Patient derived fibroblasts were transfected with FLAG-tagged TR-TUBE, as indicated. FLAG-tagged TUBE protein was affinity purified from the corresponding lysates using FLAG-beads, and the precipitates were analysed by immunoblotting using antibodies to endogenous NIX.",
    "ncbi_link": "FLAG: 
FBXL4: 26235"
  },
  {
    "caption": "(B) UbL domains mediated degradation of His3 fusion proteins with a Su9 tail, and affected yeast growth under selective condition (+3-AT, -his). Replacing UbL domains with DHFR domains rescued the growth defect. Cells expressing His3 fusion proteins in late log phase were serially diluted and stamped on selective plates. Plates were incubated at 30 ˚C for 3 daysfor imaging.",
    "ncbi_link": "His3: 
DHFR: 854411
Su9: 948275"
  },
  {
    "caption": "(B) Fluorescence profiles of cells expressing different substrates monitored by flow cytometry. UbLRad23 targeted YFP-Su9 protein for degradation. Removing the Su9 tail or replacing UbLRad23 with a DHFR domain stabilizes YFP protein in cells.",
    "ncbi_link": "Su9: 948275"
  },
  {
    "caption": "(B) In vitro degradation of Mdy2 proteins by purified S. cerevisiae proteasome. Mdy2 (red solid circles), Mdy2ΔN-95 (blue solid circles) and Mdy2-95 (green solid circles) were degraded. Removing the N-terminal domain of Mdy2 (Mdy2ΔN, black solid circles) or adding its binding partner Get4 (red open squares, dash line) or the proteasome-binding competitor UbLMdy2 (red open diamonds, dotted line) stabilized Mdy2Get4. When Mdy2 binding buried the N-terminal domain, addition of a 95 amino-acid tail derived from S. cerevisiae cytochrome b2 at the Cterminus restored degradation of Mdy2 (green open squares, dotted line). The graph plots the amount of substrate estimated by electronic autoradiography in SDS-PAGE gel bands over time as normalized to the initial substrate amount as described in Methods. Data points represent mean values determined from at least three repeat experiments; error bars indicate s.e.m.",
    "ncbi_link": "cytochrome b2: 854950
Get4: 854335
Mdy2: 854038"
  },
  {
    "caption": "(C) Degradation of Mdy2 in vivo. The steady-state accumulation of overexpressed C-terminally HA-tagged full-length Mdy2 and a mutant in which the N-terminal domain was deleted (Mdy2ΔN) in S. cerevisiae, in the absence of Get4, the presence of endogenously expressed Get4 or overexpressed Get4. Overexpressed Get4 was detected through an N-terminal Flag-tag.",
    "ncbi_link": "Get4: 854335
Mdy2: 854038"
  },
  {
    "caption": "(D) Steady-state accumulation of endogenous Mdy2 in S. cerevisiae, with deleted (get4∆) or endogenous (wt) Get4 in the presence or absence of the proteasome inhibitor bortezomib. Protein levels were determined by western blotting for the HA-tag, Flag-tag, Mdy2 or Scs2 of SDS-PAGE gels of S. cerevisiae protein extracts. Protein loading levels in each lane were estimated in all lysates by western blotting for the integral endoplasmic reticulum membrane protein Scs2.",
    "ncbi_link": "get4: 854335
Get4: 854335"
  },
  {
    "caption": "(B) In vitro degradation of Ubp6 proteins by purified S. cerevisiae proteasome. Full-length Ubp6 (Ubp6, black open circles) and a UbL deletion mutant (Ubp6ΔN, green open circles) escaped proteasome degradation. Attachment of a Cterminal 95 amino-acid tail derived from S. cerevisiae cytochrome b2 allowed the proteasome to degrade the Ubp6 proteins (Ubp6-95, black solid circles and Ubp6ΔN-95, green solid circles). The graph plots the amount of substrate estimated by electronic autoradiography in SDS-PAGE gel bands over time as normalized to the initial substrate amount as described in Methods. Data points represent mean values determined from at least three repeat experiments; error bars indicate s.e.m.",
    "ncbi_link": "cytochrome b2: 854950
Ubp6: 850562"
  },
  {
    "caption": "C) Degradation of Ubp6 proteinsin vivo. The steady-state accumulation of N-terminally HA-tagged Ubp6 and mutants in S. cerevisiae. Ubp6 and Ubp6ΔN are stable in yeast and not further stabilized by bortezomib. Attachment of a Su9 tail to the Cterminus lead to the degradation of Ubp6 and Ubp6ΔNproteins and the proteins were stabilized by bortezomib treatment.",
    "ncbi_link": "Su9: 948275
Ubp6: 850562"
  },
  {
    "caption": "(D) The steady-state accumulation of endogenous Ubp6 and Ubp6 derivatives with short (19 amino acid) or long (54 amino acid) tails at their C-termini. The 19 amino-acid tail destabilized Ubp6 and the 54-amino-acid tail lead to complete depletion of Ubp6. Protein levels were determined by western blotting for the HA-tag, Ubp6 or Scs2 in SDS-PAGE gels of S. cerevisiae protein extracts. The proteasome was inhibited by 100 µM bortezomib as indicated. Protein loading levels in each lane were normalized in all lysates by western blotting for the integral endoplasmic reticulum membrane protein Scs2.",
    "ncbi_link": "Ubp6: 850562"
  },
  {
    "caption": "(a) Electron micrographs of the IM (black arrowheads) associated with the ER (black arrows) from Atg4BC74A-expressing NIH 3T3 cells. The IM appears to expand between the two ER cisternae and forms an autophagosome. The white arrowhead indicates vesicular clusters visible in the vicinity of the IM. The white arrow indicates the autophagosome.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "(c) Localization of GFP-DFCP1 with Atg16L1 in both control and Atg4BC74A-expressing cells. Insets show enlarged images of boxed regions.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "(d-g) Gold-enhanced immunogold electron microscopy revealed that GFP-DFCP1 localized to ER-IM complexes in both control (d, e) and Atg4BC74A-expressing cells (f). Immunogold particles are indicated by small arrows. No specific labelling was observed on ER-IM complexes in cells expressing GFP (g). Large arrows and arrowheads indicate the ER and the IM, respectively. Scale bars, 200 nm in a and d-g, an d 10 μm in c.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "Atg4BC74A-expressing cells (for Atg16L1) or control cells (for PDI, COP II and β-COP) were labelled with specific antibodies against the indicated markers. The left and right anti-Atg16L1 and anti-PDI images are from two different ER-IM complexes. Arrows, arrowheads and open arrowheads indicate the ER, IMs and VTCs, respectively. Small arrows in the image from the anti-COP II experiment indicate immunogold particles. Scale bars, 200 nm.",
    "ncbi_link": "Atg4B: 66615"
  },
  {
    "caption": "Representative  images for the TIF analysis shown in (C). Shown are  POT1Y223C/- hESCs and an unedited wild-type  hESC clone (WT/WT) isolated in parallel, as well as a POT1 WT/Q623H hESC and a contemporaneously isolated hECS clones (WT/WT). Scale bars = 10µm.   Box and whisker plot (showing min, max and average) quantifying telomere-dysfunction induced foci (TIF) in two  POT1 Y223C/-  hESC lines, one POT1  Q623H/Q623H, and one POT1WT/Q623H  hESC lines compared to wild-type unedited control hESCs. Cells were analyzed 3 months post targeting. Cells were stained for TRF1  and γ-H2Ax. POT1Y223C/- cells have increased TIFs compared to an unedited wild-type cell clone, isolated and cultured in parallel (P<0.01, two-tailed Mann-Whitney test, one biological replicate).   ",
    "ncbi_link": "POT1: 25913"
  },
  {
    "caption": "B) TIF analysis of wild-type, POT1WT/Y223C hESCs, and the indicated controls using antibodies against TRF1 and γ-H2AX. Scale bars = 10µm. Lentiviral expression of TPP1∆PBD served as a positive control to demonstrate that cells have an intact telomere DNA damage  response. TPP1∆PBD infected cells were analyzed 72h post infection and without selection.",
    "ncbi_link": "POT1: 25913
TPP1: 1200"
  },
  {
    "caption": "C) Representative genotyping outcomes of hCD34+ cells nucleofected sgRNA-1, xenografted  and isolated from the bone marrow 16 weeks after transplantation into  mice  determined by NGS. Data information: The vertical dashed line shows the site of CAS9 cut and the base pairs noted in red show insertion. A dash inside a gray box indicates a deleted base pair.",
    "ncbi_link": "CAS9: 57852564"
  },
  {
    "caption": "Tumour cells were syngeneically and orthotopically co-grafted with mouse FAK-WT or FAK-KD fibroblasts. Thirty-eight days after injection, mice were euthanized. (A) Primary tumour mass quantification. Values are means ± SEM from at least 7 mice per group.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(D) Impact of conditioned media (CM) secreted by activated mouse fibroblasts expressing FAK-WT or FAK-KD on mouse BMDM-derived macrophage polarization. Relative frequencies of macrophages expressing CD80, CD86, Nos2, CD206, CMH2, Dectin, and CD163 markers acquired by flow cytometry and processed using FlowJo software.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(F) Quantitative real-time PCR conducted with gene-specific primers (CCL2, CCL5 and M-CSF) on four different FAK-I-treated (16h) and non-treated CAFs for gene expression. The normalized fold change ± SEM was calculated using the delta-delta Ct method with RSP16 as a control gene; values are mean +/- SEM. Each individual patient-derived activated fibroblasts was assigned to a specific symbol",
    "ncbi_link": "RSP16: 
CCL2: 6347
CCL5: 6352
M-CSF: 1435"
  },
  {
    "caption": "(A) Representative images of three independent scratch wound assays of co-cultivated red-labelled pancreatic tumour cells with either FAK-WT (wild-type) or FAK-KD (Kinase-dead) green-labelled fibroblasts at time zero and 46 hours (corresponding to the wound closure of co-cultured FAK-WT fibroblasts with tumour cells).",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(I) 3D reconstitution of cell invasion into collagen matrix from spheroid composed of green-labelled FAK-WT or FAK-KD fibroblasts plus red-labelled pancreatic tumour cells (ratio 1/1). Shown are representative 3D reconstitution of spheroid invasion into 2mg/ml collagen I matrix obtained using Zen software. (J-K) Quantification of fibroblast (J) or tumour cell (K) invasion within collagen matrix. Values are means ± SEM of 60 tracked cells from three independent experiments.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(A) Representative images of CK19 and α-SMA immunohistochemistry and Sirius red staining in serial sections of primary mouse tumour (graft of FAK-WT or FAK-KD fibroblasts + tumours cells at 38 days after injection) at the invasive front. Scale bar, 100 µm. Bottom: schematic organization of the cells (tumour cells in brown, CAFs in yellow and non-transformed epithelial cells in beige).",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": "(B) Representative images of ECM deposition (stained using Alexa Fluor 488 succinimidyl ester (NHS)) generated by FAK-WT or -KD activated fibroblasts during migration.",
    "ncbi_link": "FAK: 14083"
  },
  {
    "caption": " (A) Confocal images of ALIX (red), Asl (white), α-tubulin (green) and Hoechst (blue) in wild type (w1118), Sas-6c02901, DSpdG02143, cnnHK21 and γ-Tub23CPI NBs (scale bars, 5 μm). The insets show higher magnification of the boxed centrosomes",
    "ncbi_link": "cnn: 36491
γ-Tub23C: 33501
Sas-6: 43555
DSpd: 39850"
  },
  {
    "caption": "(B) The centrosomal fluorescence intensity of ALIX was measured and the graph shows the average intensity (relative to w1118 intensity) of three separate experiments (±S.E), where in total 78 w1118, 73 Sas-6c02901, 45 DSpdG02143, 61 cnnHK21 and 26 γ-Tub23CPI NBs were analyzed. Statistically significant differences are indicated (*p<0.05 and **p<0.01, Student's t-test)",
    "ncbi_link": "cnn: 36491
γ-Tub23C: 33501
Sas-6: 43555
DSpd: 39850"
  },
  {
    "caption": "(D) HeLa cells were transfected with control, Cep192 or Cep215 siRNA. Efficient depletion of Cep192 and Cep215 was confirmed by Western blotting analysis, which also showed unchanged expression levels of ALIX. Unspecific bands, below Cep192 and above Cep215, are indicated with *",
    "ncbi_link": "Cep215: 55755
Cep192: 55125"
  },
  {
    "caption": "*. (E) Control, Cep192 or Cep215 siRNA-transfected HeLa cells were immunostained with anti-ALIX (red), anti-α-tubulin (green) and Hoechst (blue). Confocal micrographs are presented and the insets show the indicated centrosomes (arrows) at higher magnification (scale bars, 5 μm)",
    "ncbi_link": "Cep215: 55755
Cep192: 55125"
  },
  {
    "caption": "(F) The centrosomal ALIX fluorescence intensity was measured and the graph shows the average intensity (relative to control siRNA cells) of three independent experiments (±S.E), where in total 41 control siRNA, 40 Cep192 siRNA and 39 Cep215 siRNA-transfected cells were analyzed, **p< 0.01, Student's t-test",
    "ncbi_link": "Cep215: 55755
Cep192: 55125"
  },
  {
    "caption": " (A) Brains were dissected from w1118, alix1, alix-l/CyO; alix1 and mud4 larvae and stained with anti-Bazooka (red), anti-Cnn (white) and Hoechst (blue). Representative confocal images are shown. Scale bars, 5 μm. The graph summarizes the average variation of the relative spindle angles in w1118 (n=74), alix1 (n= 96), alix-l/CyO; alix1 (n= 78) and mud4 (n=32) NBs (four separate experiments) (±S.E). Compared to w1118 or alix-l/CyO; alix1 NBs both  alix1 and mud4 NBs showed greater variation in MS orientation (***p<0.001, ANOVA) ",
    "ncbi_link": "alix: 43330
mud: 44839"
  },
  {
    "caption": "(C) Brain lysates of w1118, alix1 and alix-l/CyO; alix1 larvae were immunoblotted for ALIX, α-tubulin and GAPDH (loading control)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(D) Time-lapse imaging of Asl-YFP, α-tubulin-GFP in control (left panel) and alix3 (right panel) mutant SOPs of the pupal notum. SOPs were identified by the apical meshwork of MTs (not shown). Time is indicated in min:sec. Mitotic cells are indicated with arrows. Scale bar represents 5 μm",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(E) Quantification of the rotation angle (±S.E) in control (n=26) and alix3 (n=45) mutant SOPs (at least three separate experiments). **p<0.01 (Student's t-test) compared to control",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(G) Western blotting analysis of lysates from control Asl-YFP, α-tubulin-GFP and Asl-YFP, α-tubulin-GFP; alix3 pupae showed absence of ALIX in the alix3 homozygous mutant and unchanged expression of α-tubulin and GAPDH (loading control)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": " (A) Ovaries of adult female flies (w1118, alix1 and alix-l/CyO; alix1) were stained with rhodamine-phalloidin (red), anti-α-tubulin (green), anti-Cnn (white) and Hoechst (blue). Typical confocal micrographs of metaphase FECs are presented and the apical membrane facing the egg chamber lumen is indicated with *. Scale bar, 5 μm. The MS orientation was measured and the graph shows the average percentage of FECs (w1118, n=45, alix1, n=45, alix-l/CyO; alix1, n=39, from three independent experiments) with the indicated relative spindle angle (±S.E). Statistically significant difference is indicated as ***p<0.001 (ANOVA)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(C) Lysates of ovaries from w1118, alix1 and alix-l/CyO; alix1 flies were immunoblotted for ALIX, α-tubulin and GAPDH (loading control)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(D) The MS orientation was determined in metaphase cells in organoids of Caco-2 cells transfected with control (n=75), ALIX (n=88) or NuMA (n=79) siRNA (from three independent experiments). The graph shows the average percentage of Caco-2 cells with the indicated relative spindle angle (±S.E). Greater spindle angle variation was observed in ALIX- and NuMA-depleted cells compared to control cells (***p<0.001, ANOVA). Representative confocal images are shown where the cells are stained with rhodamine-phalloidin (red), α-tubulin (green) and Hoechst (blue). The apical membrane facing the lumen of the organoid is marked (*). Scale bar, 5 μm",
    "ncbi_link": "NuMA: 4926
ALIX: 10015"
  },
  {
    "caption": "(E) Lysates of control, ALIX or NuMA-depleted Caco-2 cells were immunoblotted for NuMA, ALIX, α-tubulin and GAPDH (loading control)",
    "ncbi_link": "NuMA: 4926
ALIX: 10015"
  },
  {
    "caption": " (A) The MARCM strategy was used to generate alix mutant NBs clones (FRT82B, alix1) or genetic equivalent control clones (FRT82B con) in the larval brain. Dissected brains were immunostained with anti-α-tubulin (red) and Hoechst (blue). Recombinant NBs are positively marked with GFP (green) and outlined. The presence or lack of astral MTs is indicated with arrows or asterisks, respectively. Scale bars, 5 μm. The average intensity of astral, total and astral/total MT (±S.E) in GFP-positive relative to GFP-negative control cells (set to 100%, indicated as dotted line in the graph) was calculated from three separate experiments (including 13 GFP-negative FRT82B con NBs, 11 GFP-positive FRT82B con NBs, 10 GFP-negative FRT82B, alix1 NBs and 8 GFP-positive FRT82B, alix1 NBs) (*p<0.05 and **p<0.01, Student's t-test) ",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(B) HeLa cells depleted of ALIX or not were immunostained with anti-α-tubulin (red), anti-Pericentrin (green) and Hoechst (blue). Representative confocal images are presented. Scale bars, 5 μm. The graph shows MT intensities as percentage of control cells (±S.E) obtained from 99 control and 90 ALIX siRNA transfected cells (data obtained from six separate experiments). Significant differences are noted as *p<0.05 and ***p<0.001 (Student's t-test)",
    "ncbi_link": "ALIX: 10015"
  },
  {
    "caption": "(C, D) Regrowth of MTs after cold-induced depolymerization was performed using brains of w1118 and alix1 larvae, stained with anti-α-tubulin (red), anti-Bazooka (green) and Hoechst (blue) (C Typical confocal images showing MT-regrowth at given time points are shown (scale bars, 5 μm). The graphs show the time-dependent MT intensities relative to the respective 0''-samples (±S.E) calculated from three independent experiments. In (C) 46, 64, 65 and 48 w1118 NBs and 73, 37, 44 and 49 alix1 NBs from 0, 30, 60 and 300'' were analyzed, respectively (*p<0.05)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(C, D) Regrowth of MTs after cold-induced depolymerization was performed usin HeLa cells depleted of ALIX or not stained with anti-α-tubulin (white) and anti-Pericentrin (green) (D) Typical confocal images showing MT-regrowth at given time points are shown (scale bars, 5 μm). The graphs show the time-dependent MT intensities relative to the respective 0''-samples (±S.E) calculated from three independent experiments In (D) 47, 40 and 42 control cells and 48, 47 and 47 ALIX-depleted cells were calculated 0, 30'' and 420'' after regrowth, respectively (*p<0.05)",
    "ncbi_link": "ALIX: 10015"
  },
  {
    "caption": "(E) Brains dissected from control (FRT82B con) or alix1 (FRT82B, alix1) larvae were immunostained with anti-γ-tubulin (red) and Cnn (white, left panel) or anti-Dgrip91 (red) and α-tubulin (white, right panel), as well as Hoechst (blue). Recombinant NBs are positively marked with GFP (green). The confocal images show typical accumulation of centrosomal γ-tubulin or Dgrip91, and the insets zoom in at the indicated centrosomes. Scale bars, 5 μm. The intensities of γ-tubulin, Dgrip91 and Cnn in control NBs (GFP-negative, set to 100 %) and GFP-positive, recombinant NBs are presented in the table (±S.E), also indicating the number of NBs quantified (n) from three separate experiments (*p<0.05)",
    "ncbi_link": "alix: 43330"
  },
  {
    "caption": "(H) HeLa cells depleted of ALIX or not grown on coverslips were stained with anti-γ−tubulin (white), anti-Pericentrin (red) and Hoechst (blue) before being examined by confocal fluorescence microscopy. The confocal images and insets show the centrosomal accumulation of γ-tubulin and Pericentrin. Scale bars, 5 μm. The graph presents the average centrosomal intensities of γ-tubulin and Pericentrin relative to control cells (set to 100%) calculated from three independent experiments (10 cells per condition/experiment) (±S.E). Significant difference is noted as **p<0.01 (Student's t-test)",
    "ncbi_link": "ALIX: 10015"
  },
  {
    "caption": "(I) Lysates of control or ALIX-depleted HeLa cells were immunoblotted for ALIX, γ-tubulin, α-tubulin and GAPDH (loading control)",
    "ncbi_link": "ALIX: 10015"
  },
  {
    "caption": " (A) The MS orientation was determined in metaphase NBs from brains dissected from wild type (w1118), alix1, γ−Tub23CPI or γ−Tub23CPI; alix1 larvae. Compared to w1118, significantly greater variation in the relative spindle angles was observed in alix1 NBs and γ−Tub23CPI; alix1 NBs (*p<0.05, ANOVA). The γ−Tub23CPI;alix1 NBs displayed significantly greater variation of their spindle orientations than either alix1 or γ−Tub23CPI NBs (*p<0.05, ANOVA). The graph shows the average percentage of NBs with the indicated relative spindle angles (±S.E) from in total 57 w1118 NBs, 55 alix1 NBs, 76 γ−Tub23CPI NBs and 62 γ−Tub23CPI; alix1 NBs (three independent experiments) ",
    "ncbi_link": "alix: 43330
γ−Tub23C: 33501"
  },
  {
    "caption": "(C) Dissected brains of w1118, alix1, γ−Tub23CPI and γ−Tub23CPI;alix1 larvae were subjected to MT regrowth assay and stained with anti-α-tubulin (red), anti-Cnn (white) and Hoechst (blue). Representative images of NBs after 0 and 60 seconds regrowth are presented. Scale bars, 5 μm",
    "ncbi_link": "alix: 43330
γ−Tub23C: 33501"
  },
  {
    "caption": "(D) The MT-intensities after 0 and 60 seconds regrowth were determined, here presented as the average of three separate experiments (± S.E) where in total 27 w1118-0'', 28 w1118-60'', 26 alix1-0'', 19 alix1-60'', 28 γ−Tub23CPI-0'', 26 γ−Tub23CPI-60'', 28 γ−Tub23CPI;alix1-0'' and 23 γ−Tub23CPI;alix1-60'' NBs were analyzed. Compared to w1118-NBs, significantly less MT polymerized in alix1, γ−Tub23CPI or γ−Tub23CPI;alix1 NBs (*p<0.05, ANOVA)",
    "ncbi_link": "alix: 43330
γ−Tub23C: 33501"
  },
  {
    "caption": "(E) The relative spindle angle between the polarity axis perpendicular to the apical phalloidin-stained F-actin surface and the MS was determined in metaphase Caco-2 cysts cells transfected with control, ALIX and/or γ-tubulin siRNA (29, 29, 18 and 32 metaphase cells, respectively, were analyzed from three separate experiments). Compared to control cells, depletion of either ALIX or both ALIX and γ-tubulin, induced a significantly increased randomization of the relative spindle angles (**p<0.01 and ***p<0.001, ANOVA). Caco-2 cells depleted of ALIX+γ-tubulin showed a greater variation in the spindle angles compared to depletion of ALIX or γ-tubulin (*p<0.05, ANOVA). ALIX-depleted cells showed greater spindle angle-variation than γ-tubulin-depleted cells (*p<0.05, ANOVA)",
    "ncbi_link": "ALIX: 10015
γ-tubulin: 7283"
  },
  {
    "caption": " (A) HeLa cells transfected with control or ALIX siRNA were fixed, permeabilized and stained with anti-MAP1S (red), anti-γ-tubulin (white) and Hoechst (blue). Interphase cells are shown and the insets show close ups of the centrosomes. Scale bars, 5 μm. (B) The fluorescence intensity of centrosomal MAP1S was determined and the graph shows the average of three independent experiments (± S.E), in which in total 52 control and 36 ALIX siRNA cells were analyzed. Significant difference is indicated as *p<0.05 (Student's t-test) ",
    "ncbi_link": "ALIX: 10015"
  },
  {
    "caption": "(C) HeLa cells were transfected with control, ALIX, MAP1S or ALIX+MAP1S siRNA and the expression of ALIX, MAP1S and GAPDH (loading control) was determined by Western blotting analysis. Representative results are presented",
    "ncbi_link": "MAP1S: 55201
ALIX: 10015"
  },
  {
    "caption": "(G) HeLa cells transfected with control or ALIX siRNA grown on coverslips were transiently transfected with pEYFP-C1 (green), pEYFP-MAP1S (green), pEGFP-C1 (green) or pEGFP-CLASP2α and immunostained with anti-α-tubulin (white), anti-Pericentrin (red) and Hoechst (blue). Scale bars, 5 μm",
    "ncbi_link": "CLASP2α: 23122
MAP1S: 55201
ALIX: 10015"
  },
  {
    "caption": "(H) The lengths and numbers of astral MTs of HeLa cells treated as in (G) were measured (LSM software, version 3.2). The graphs show the average numbers (±S.E) based on calculating 30 control siRNA+YFP cells, 23 control siRNA+YFP-MAP1S cells, 30 ALIX siRNA+YFP cells, 30 ALIX siRNA+YFP-MAP1S cells, 28 control siRNA+GFP cells, 30 control siRNA+GFP-CLASP2α cells, 30 ALIX siRNA+GFP cells and 29 ALIX siRNA+GFP-CLASP2α cells from three separate experiments (*p<0.05, Student's t-test), respectively",
    "ncbi_link": "CLASP2α: 23122
MAP1S: 55201
ALIX: 10015"
  },
  {
    "caption": " Mean IC50 values (µM) for APR-246 +/- 20 μM MK-571 of 21 cell lines. *p < 0.0001, Wilcoxon test. Each dot represents one cell line. Mean IC50 values and n shown in Table S1. ZIP synergy scores of most synergistic area sub-grouped according to TP53 gene status for 21 cell lines. Each dot represents one cell line. Scores and n are shown in Table S1. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Western blot analysis of MRP1 (Cell Signaling.), p53 (DO-1) and GAPDH of HCT116 WT and R248W cells 48h after transfection with negative control siRNAs or siRNAs targeting MRP1 or p53.",
    "ncbi_link": "MRP1: 4363
p53: 7157"
  },
  {
    "caption": "Growth suppression (WST-1 assay) of HCT116 WT and R248W cells transfected with MRP1 siRNA (n ≥ 5 and n ≥ 2 respectively) after 48h APR-246 treatment. Indicated values are average of four individual siRNAs targeting MRP1 and two individual negative control siRNAs. Data and n of individual siRNAs are shown in Fig S1J, data is also part of Fig 7B.",
    "ncbi_link": "MRP1: 4363"
  },
  {
    "caption": "Western blot analysis of MRP1 (Cell Signaling.), p53 (DO-1) and GAPDH of HCT116 WT and R248W cells 72h after transfection with empty vector (EV) and MRP1 expression vector.",
    "ncbi_link": "MRP1: 4363"
  },
  {
    "caption": "Growth suppression (WST-1 assay) of HCT116 WT and R248W cells transfected with empty vector (EV) and MRP1 vector after 72h APR-246 treatment (n = 4). Data is also part of Fig S7E.",
    "ncbi_link": "MRP1: 4363"
  },
  {
    "caption": "Growth of Eso26 xenografts (R248W mutant TP53) in mice treated with vehicle, APR-246 (50mg/kg), MK-571 (50mg/kg) or APR-246 and MK-571 for 16 days. p values determined by one-way ANOVA with Tukey's correction at day 18, n is indicated in the figure.   Kaplan-Meier plot of time to reach 1400 mm3 tumor volume in mice treated with vehicle, APR-246 (50mg/kg), MK-571 (50mg/kg) or APR-246 and MK-571 for 16 days. Mice that were culled at ethical endpoints prior to reaching a tumor volume of >1400mm3 are marked as censored observations. p values were determined by Log-rank (Mantell-Cox) test between different treatment groups. n is indicated in the figure.   ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "14C accumulation (cpm/mg x ml-1) in HCT116 WT and R248W cells (n ≥ 3 and ≥ 2) transfected with MRP1 siRNAs after 24h of 14C-APR-246 treatment. Indicated values represent four individual MRP1 siRNAs and two individual negative control (Ctrl) siRNAs, where each dot is an individual siRNA. Mean of 14C-accumulation after treatment and n with individual siRNA sequences is shown in Table S4. *p = 0.04 and for R248W p = 0.06, Wilcoxon matched pairs signed rank test.",
    "ncbi_link": "MRP1: 4363"
  },
  {
    "caption": "APR-246 content in OVCAR-3 cells (TP53 R248Q) 24h after treatment with APR-246 +/- MK-571, (n = 3). Data information: Indicated values are assessed by LC-MS. Data are represented as mean ± SEM. See also Appendix Figure S4.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Mean IC50 (µM) values of APR-246 in 17 different cell lines (n ≥ 3) as shown by WST-1. *p = 0.03, Mann Whitney test. Mean IC50 (µM) values for APR-246 treatment and n for individual cell lines are also shown in Fig 1C and listed in Table S1. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Box-and-whisker plot of Pearson correlations between PRIMA-1 area-under-the-curve (AUC) and the levels of 225 different metabolites from the DepMap portal. Central band indicates median, boxes indicate 25th and 75th percentile, and whiskers show 2.5th and 97.5th percentile outlier metabolites. High GSH and GSSG (in red) correlate with low PRIMA-1 sensitivity. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " Total intracellular glutathione (GSH+GSSG) as shown by glutathione reductase (GR) re-cycling assay in H1299 R175H (tet-off) (+/- doxycycline) and H1299 -/- cells 24h after seeding (n = 3). Indicated values are fold change compared to mutant TP53 cells. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " Total intracellular glutathione (GSH+GSSG) as shown by GR re-cycling assay in untreated HCT116 (R248W, WT and -/-) cells 48h after seeding (n = 3, 5 or 2 respectively). Indicated values are fold change to mutant TP53 cells. Part of this data is shown in Fig. EV4. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Thiol tracker staining by flow cytometry 48h after seeding of the indicated untreated cells (n = 2) Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5.",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " Correlation between 14C accumulation (cpm/mg x ml-1) after treatment with 25 µM 14C-APR-246 and IC50 (µM) values for APR-246 in 11 cell lines (n ≥ 3) (r = -0.66, p = 0.03, Pearson correlation). Each dot represents one cell line, 14C accumulation data are shown in Fig 3B and values and n for individual cell lines are listed in Table S1 and S3. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " ABCC1 mRNA Expression, RSEM (Batch normalized from Illumina HiSeq_RNASeqV2) in lung cancer (luad & lusc studies, *p<0.0001) and colon adenocarcinoma (coad study, *p=0.005) grouped into having no alterations or putative driver missense mutations in TP53. Statistical analysis by Mann Whitney test, n is indicated in the figure. Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "ABCC1: 4363
TP53: 7157"
  },
  {
    "caption": " 14C accumulation (cpm/mg x ml-1) in H1299 R175H cells (+/- doxycycline) and H1299 -/- cells after 24h treatment with 14C-APR-246 (n = 2). Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " Growth suppression in H1299 R175H cells (+/- doxycycline) and H1299 -/- cells treated for 72h with APR-246 as shown by WST-1 assay (n = 3). Data information: TP53 status is indicated for each cell line. Data are represented as mean ± SEM. See also Figure EV5 and Appendix Figure S5. ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Intracellular oxidized glutathione (GSSG per 106 cells) as shown by LC-MS in OVCAR-3 (R248Q TP53) cells at 24h treatment with APR-246 +/- MK-571 (n = 3).",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": " 14C accumulation (cpm/mg x ml-1) in HCT116 WT and R248W mutant TP53 cells +-transfected with MRP1 or xCT siRNA following 24h of 14C -APR-246 treatment +/- MK-571 . Indicated values are mean values from four MRP1 siRNAs (n ≥ 3), three xCT siRNAs (n = 1-2) and two control siRNAs (n ≥ 3). Mean 14C -accumulation after treatment and n of individual siRNAs is shown in Table S4 . Data for control and MRP1 siRNA after 14C -APR-246 treatment is also shown in Fig 3D. ",
    "ncbi_link": "MRP1: 4363
xCT: 23657
TP53: 7157"
  },
  {
    "caption": " Growth suppression in HCT116 WT and R248W cells transfected with MRP1 or xCT siRNA after 48h of APR-246 treatment as shown by WST-1 assay. Indicated values are mean values of four MRP1 siRNAs (n ≥ 3), three xCT siRNAs (n =1-2) and two control siRNAs (n ≥ 3). Data for control and MRP1 siRNA after APR-246 single treatment are also included in Fig 1I. Values and n for individual siRNA shown in Fig. S7C. ",
    "ncbi_link": "MRP1: 4363
xCT: 23657"
  },
  {
    "caption": " Total intracellular glutathione (GSH + GSSG per 106 cells) in HCT116 WT cells as shown by GR re-cycling assay 48h post transfection of siRNA. Indicated values are means from four MRP1 siRNAs (n = 3), two xCT siRNA (n = 2-3) and two control siRNA (n = 2-3). ",
    "ncbi_link": "MRP1: 4363
xCT: 23657"
  },
  {
    "caption": " OVCAR-3 (R248Q TP53) confluence by IncuCyte® during 72h treatment with APR-246 +/- MK-571 or sulfasalzine (SSZ) (n = 3). Part of the data are shown in Fig 1G. Growth suppression in OVCAR-3 cells as determined by IncuCyte® during 72h treatment with APR-246 +/- MK-571 or sulfasalazine (SSZ) depicted as heatmaps (n = 3). ",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "(A) qRT-PCR analysis of SUMO-modifying proteins and enzymes in cortex and striata of WT mice at 12 weeks. Relative expression for all the SUMO enzymes is normalized to mouse β-actin.",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "(B and C) qRT-PCR of SUMO mRNAs from 12-week-old WT and R6/2 mouse cortex (B) and striatum (C). SUMO enzyme mRNAs are differentially expressed in R6/2 versus control with statistically significant increases in SENP1 (p = 0.01), SENP3 (p = 0.02), and SUMO-1 (p = 0.003) in cortex and SENP1 (p = 0.02), SENP6 (p = 0.04), PIAS3 (p = 0.007), SUMO-1 (p = 0.02), and SUMO-2 (p = 0.02) in striatum. Samples were analyzed in quadruplicate and normalized to mouse β-actin. Data are shown as R6/2 expression relative to WT levels set at 1 for each enzyme with ± SD (n = 4). *p < 0.05. n.s., not significant.",
    "ncbi_link": "β-actin: 
PIAS3: 229615
SENP1: 223870
SENP3: 80886
SENP6: 215351
SUMO-1: 22218
SUMO-2: 170930"
  },
  {
    "caption": "(A) HeLa cells transfected with His-tagged HTTex1p (46Q) or 46QP-K6,9,15R (3R) along with GFP-SUMO-1 or GFP-SUMO-2, lysed under denaturing conditions, and nickel purified (Ni-NTA). Unmodified HTT-46Q is indicated by the arrow and SUMO-modified HTT by the boxed region. The lysine mutant (3R) serves as a negative control. Ni-NTA represents nickel-purified His-tagged HTT, and WC TCA represents 10% of the whole-cell lysate expression of HTT and myc-actin (transfection control). HTT is modified by SUMO-1 (left) and SUMO-2 (right).",
    "ncbi_link": "HTT: 3064
SUMO-1: 7341
SUMO-2: 6613"
  },
  {
    "caption": "(B) SUMO isopeptidases (SENP1, SENP2, SENP3, SENP5, and SENP6) modulate SUMO-modified HTT when overexpressed together with HTT (46QP-H4 or 3R) and SUMO-1 (GFP-SUMO-1). SENP1, SENP2, and SENP6 decrease HTT SUMOylation. Graph depicts quantitation of western blot using the Odyssey Infrared Imaging System (LI-COR) to calculate the ratio of HTT purified versus the HTT modified by SUMO multiplied by 100.",
    "ncbi_link": "HTT: 3064
SENP1: 29843
SENP2: 59343
SENP3: 26168
SENP5: 205564
SENP6: 26054"
  },
  {
    "caption": "(C) Titration of SUMO-1. Denaturing nickel purification of HTTex1p (46QP-H4) following transfection with decreasing amounts of SUMO-1 reduces the amount of SUMO-modified HTT to undetectable levels. The Ni-NTA blot displayed in the gray scale shows purified HTTex1 and SUMO-modified HTTex1 using HTT antibody. Note that 0.5 μg of SUMO-1 (¼ the amount of SUMO-1 cDNA ) was used for identifying the SUMO-1 E3 ligase for HTTex1p. Graph depicts quantitation of western blot using the Odyssey Infrared Imaging System to calculate the ratio of HTT purified versus the HTT modified by SUMO multiplied by 100. Note that all experiments were performed in triplicate, and a representative figure is shown.",
    "ncbi_link": "HTT: 3064
SUMO-1: 7341"
  },
  {
    "caption": "(A) Under limiting SUMO conditions (1/4 SUMO-1, lanes 3-9), PIAS1 increases HTT-SUMO modification above 1/4 SUMO alone. Purified HTT (arrow) and SUMO-HTT (boxed region) were detected using anti-HTT. Graph depicts quantitation of the Ni-NTA western blot using the Odyssey Infrared Imaging Software (LI-COR) to calculate the ratio of HTT purified versus the HTT modified by SUMO multiplied by 100.",
    "ncbi_link": "HTT: 3064
PIAS1: 8554"
  },
  {
    "caption": "(B) Western analysis of overexpression of HTTex1 (46QP-H4 or 3R), SUMO-2 (GFP-SUMO-2), and all the PIAS proteins (PIAS1, PIASxα, PIASxβ, PIAS3, and PIASy). Under nonlimiting SUMO-2 conditions, PIAS1 enhances SUMO modification of HTT. WC TCA shows overall myc-actin (transfection control) and HTT levels. Graph quantitating the ratio of HTT purified versus the HTT modified using the Odyssey (LICOR).",
    "ncbi_link": "HTT: 3064
PIAS1: 8554
PIASxα: 9063
PIASxβ: 9063
PIAS3: 10401
PIASy: 51588"
  },
  {
    "caption": "(C) Left panel is the autoradiography results of a GST pull-down assay showing that radiolabeled human PIAS1 interacts with HTTex1p. Right panel is a phosphorimager analysis of GST pull-downs, performed in triplicate, showing the percentage of 35S-labeled PIAS protein that bound the GST proteins: GST alone, unexpanded HTT with and without the proline-rich region (20QP and 20Q), expanded HTT with and without the proline-rich region (51QP and 51Q), and the proline-rich region alone (Pro). Error bars were calculated as an estimate of SE = STDEV(n)/SQRT(n-1).",
    "ncbi_link": "HTT: 3064"
  },
  {
    "caption": "(B) Longer HTT polypeptides are modified by SUMO-1. Western blot overexpressing HTTex1p (46QP-H4 or 3R), unexpanded HTT-586 fragment (25Q-586 or 25Q-3R-586 aa), and expanded HTT-586 fragment (137Q-586 or 137Q-3R-586 aa) with SUMO-1 (GFP-SUMO-1). Cell lysates were subjected to HTT immunoprecipitation (IP) using HTT antibody. Western analysis performed with the Odyssey (LI-COR) allows detection of HTT (data not shown) and SUMO simultaneously and shows that all forms of HTT are SUMO-1 modified using the anti-GFP antibody. HTTex1p is covalently SUMO-1 modified (lane 3), and the modification disappears when Lys are mutated to Arg (3R) (lane 4). Both unexpanded (lane 4 and 5) and expanded HTT-586 fragments (lane 6 and 7) are covalently SUMO-1 modified in both the presence and absence of the three Lys in the N-terminal region of HTT (3R). Free SUMO-1 is indicated with the arrow, and SUMO-modified HTT is indicated by the boxes. Inset on the right, from a replicate experiment, shows comigration of expanded HTT (anti-HTT) and SUMO-1 (anti-GFP) displayed in the gray scale and in color when the two antibodies are merged (HTT in red, SUMO-1 in green, and yellow when colocalizing).",
    "ncbi_link": "HTT: 3064
SUMO-1: 7341"
  },
  {
    "caption": "(C) Bait plasmids (HTT-586-25Q or HTT-586-73Q aa) were transformed into the L40ccua MATa yeast strain. Yeast clones encoding bait proteins were individually mated against a matrix of MATα yeast clones encoding 16,888 prey proteins (with Gal4 activation domain fusions) using pipetting and spotting robots. Diploid yeasts were spotted onto SDIV (-Leu-Trp-Ura-His) agar plates for selection of PPIs as well as nylon membranes placed on SDIV agar plates for β-galactosidase assays. After 5-6 days of incubation at 30ºC, digitized images of the agar plates and nylon membranes were assessed for growth and β-galactosidase activity using the software Visual Grid (GPC Biotech).",
    "ncbi_link": "Gal4: "
  },
  {
    "caption": "(D) Overexpression of PIAS1 alone, with unexpanded HTT constructs (25Q-586 aa) plus SUMO-1 (GFP-SUMO-1), shows that PIAS1 binds both full-length HTT and HTT-586 fragment (25Q-586 aa). WT HTT was used in these experiments to preclude confounding aggregation effects. Western analysis detection was performed using Odyssey and is displayed in the gray scale but is shown in color on the merge (HTT is red, and PIAS1 is green). WB, western blot.",
    "ncbi_link": "HTT: 3064
PIAS1: 8554
SUMO-1: 7341"
  },
  {
    "caption": "(E) HeLa cells overexpressing either expanded 586 aa-HTT or the phosphomimetic (S13,16D = DD) with SUMO-2 plus and minus PIAS1. HTT was purified by IP using hydrazide beads (Bioclone) crosslinked to HTT (Enzo) antibody and subjected to western analysis using anti-HTT (MAB5490). Arrows indicate SUMO-2-modified HTT.",
    "ncbi_link": "HTT: 3064
PIAS1: 8554
SUMO-2: 6613"
  },
  {
    "caption": "(F) IP of HTT with hydrazide-linked beads shows that both unexpanded and expanded HTT 586 aa phosphomimetics (S13, 16D-586 aa) are modified by SUMO-2. Arrows indicate SUMO-conjugated HTT. Note that all experiments including the Y2H assay were done in triplicate; representative experiments are shown. Arrows indicate SUMO-2-modified HTT.",
    "ncbi_link": "HTT: 3064
SUMO-2: 6613"
  },
  {
    "caption": "(A) Western analysis of whole-cell lysates from HeLa cells transfected with His-SUMO-1 or SUMO-2 and/or 97Q-HTT exon 1 and treated with 5 μM MG132 for 18 hr. Lysates were separated using differential centrifugation into a detergent-soluble fraction (SOLUBLE) with 1% Triton X-100 and a detergent-insoluble fraction (INSOLUBLE) with 4% SDS. Western blot probed with anti-HTT shows full-length endogenous HTT in the SOLUBLE fraction (upper arrow) and 97Q-HTTex1 (lower arrow) (left panel). In the INSOLUBLE fraction, HTT HMW species are indicated by the bracket and asterisks (right panel).",
    "ncbi_link": "HTT: 3064
SUMO-1: 7341
SUMO-2: 6613"
  },
  {
    "caption": "(B) MG132 and SUMO-2 cause mutant HTT to accumulate as HMW species (bracke and asterisk). Western blot showing IP with HTT antibody crosslinked beads from the detergent-insoluble fraction probed with the anti-HTT antibody.",
    "ncbi_link": "HTT: 3064
SUMO-2: 6613"
  },
  {
    "caption": "(C) Mutant HTT (97Q-Httex1) fibrils are detected with anti-HTT in the insoluble fraction with treatment of MG132 or addition of exogenous SUMO-2.",
    "ncbi_link": "HTT: 3064
SUMO-2: 6613"
  },
  {
    "caption": "(D) Western blot with increasing concentrations of SUMO-2 detected with anti-His antibody (left panel). Middle panel is the same western blot probed with anti-HTT showing soluble forms of HTT. Right panel presents western blot from detergent-insoluble fraction with monomeric HTT (97Q) at 55 kDa, and the asterisk (*) indicates the HMW species. Note that all experiments were performed in triplicate; representative figures are shown.",
    "ncbi_link": "SUMO-2: 6613"
  },
  {
    "caption": "(A) Western blot analysis of HeLa cells over-expressing exogenous PIAS1 in the presence of mutant HTT (97Q) when separated into detergent-soluble and detergent-insoluble fractions. No difference is detected in monomeric HTT (top panel, Soluble), but HMW HTT levels increase with PIAS1 overexpression. Anti-PIAS1 antibody (Invitrogen) was used to detect PIAS1.",
    "ncbi_link": "PIAS1: 8554"
  },
  {
    "caption": "(B) Acute knockdown of PIAS1 decreases HMW HTT species in the detergent-insoluble fraction. PIAS1 knockdown is detected in detergent-soluble and -insoluble fractions using anti-PIAS1 antibody.",
    "ncbi_link": "PIAS1: 8554"
  },
  {
    "caption": "(C) Drosophila melanogaster expressing mutant HTTex1p (93Q) in a reduced Su(var)2-10/dPIAS genetic background exhibits statistically significantly reduced photoreceptor neuron degeneration (left panel, p = 0.033) when comparing dPIAS/+ to +/+ flies and increased overall survival (right panel, p = 0.047) when comparing dPIAS1/+ to +/+ flies. Significance was measured by Student's t test.",
    "ncbi_link": "HTT: 3064
dPIAS: 35927
Su(var)2-10: 35927"
  },
  {
    "caption": "(C) Survival curves of GRWT and GRDim mice treated for 7 days with 25 mM ZnSO4 in the drinking water and challenged, i.p., with 50 µg (GRWT) or 12.5 µg (GRDim) TNF, solved in sterile PBS, per 20 g bodyweight. No deaths occurred later than 50 h after TNF injection. Results represent combined data of 2 experiments.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Zinc levels in the serum after 7 days of 25 mM ZnSO4 supplementation to the drinking water of GRWT and GRDim mice (E, N=6-9).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "(F) Agtpbp1 gene-expression measured with RT-qPCR in the ileum of GRWT and GRDim mice treated for 7 days with 25 mM ZnSO4 in the drinking water (N=3 per group).",
    "ncbi_link": "Agtpbp1: 67269
GR: 14815"
  },
  {
    "caption": "(G) Survival curves of GRfl/fl and GRVillKO mice treated for 7 days with 25 mM ZnSO4 in the drinking water and challenged, i.p., with 35 µg TNF, solved in sterile PBS, per 20 g bodyweight. No deaths occurred later than 150 h after TNF injection. Results represent combined data of 6 experiments.",
    "ncbi_link": "GR: 14815
Vill: 22349"
  },
  {
    "caption": "(H) Mouse Nr3c1 gene-expression measured with RT-qPCR in the intestinal epithelial cells (IECs) of GRfl/fl and GRVillKO mice (N=3-6). Hprt and Villin were used as house-keeping genes.",
    "ncbi_link": "Hprt: 
Villin: 
Nr3c1: 14815
GR: 14815
Vill: 22349"
  },
  {
    "caption": "(I) Zinc levels in the serum after 7 days of 25 mM ZnSO4 supplementation to the drinking water of GRfl/fl and GRVillKO mice (N=9 per group).",
    "ncbi_link": "GR: 14815
Vill: 22349"
  },
  {
    "caption": "(D) Regression curve plotting LFCs of genes induced by ZnSO4 in GRWT and GRDim mice, as measured by RNA-seq in ileum samples. All genes, induced in ileum by DEX in GRWT with LFC>0.8, p<0.05 are considered, while these genes with p<0.05 in GRDim were considered. The slope of the correlation curve as well as Pearson correlation coefficient were calculated by Graphpad Prism.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Transcriptional downregulation of ISRE/IRF genes in the intestinal epithelium by zinc part 1. RNA-seq experiment of GRWT and GRDim mice which received normal drinking water or drinking water containing 25mM ZnSO4 for 1 week. Ileum was sampled and RNA-seq performed (N=5-6 per group). Genes downregulated by zinc compared to water control animals (LFC<0.8 and p<0.05) were considered. (C) Heat map of a selection of the 48 genes of Fig 3B.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "(A-B) Expression levels (RT-qPCR data) of Mlkl and Zbp1, from the collection of 48, in ileum biopsy samples, showing the reducing effects of zinc in both GRWT and GRDim mice, and the higher expression in GRDim compared to GRWT (N=4-6/group).",
    "ncbi_link": "Mlkl: 74568
GR: 14815
Zbp1: 58203"
  },
  {
    "caption": "RT-qPCR data of Mlkl, Zbp1 in ileum biopsy samples of C57BL/6J mice or different TLR full knockout mice. (N=4/23 per group)",
    "ncbi_link": "Mlkl: 74568
Zbp1: 58203"
  },
  {
    "caption": "RT-qPCR data of Ripk3, in ileum biopsy samples of C57BL/6J mice or different TLR full knockout mice. (N=4/23 per group)",
    "ncbi_link": "Ripk3: 56532"
  },
  {
    "caption": "RT-qPCR data of Mlkl , in ileum biopsy samples of C57BL/6J mice treated with normal drinking water or 25 mM ZnSO4 in the drinking water for 1 week, either or not pretreated with antibiotics (AB) for three weeks. (N=5 per group)",
    "ncbi_link": "Mlkl: 74568"
  },
  {
    "caption": "RT-qPCR data of Zbp1, in ileum biopsy samples of C57BL/6J mice treated with normal drinking water or 25 mM ZnSO4 in the drinking water for 1 week, either or not pretreated with antibiotics (AB) for three weeks. (N=5 per group)",
    "ncbi_link": "Zbp1: 58203"
  },
  {
    "caption": "(D-F) RT-qPCR measurement of mRNA levels of Defa6 and Lyz2, two Paneth cell markers, and Ripk3, a TNF-induced cell-death gene, in ileum of the experiment in A.",
    "ncbi_link": "Defa6: 13240
Lyz2: 17105
Ripk3: 56532"
  },
  {
    "caption": "Monocolonization experiment. Mice (N=5 all groups) were treated with H20 or ZnSO4 for 7 days, after which the ZnSO4 was removed and replaced by H20. 12h and 24h later, the mice were transplanted with PBS, 108 Staphylococcus sciuri (in 100 ul), and 3h later a lethal dose of TNF (35 µg/mouse) was injected In a second experiment (G-I) (N=4 all groups) with S. sciuri colonization, Zbp1 and Stat1, two key ISRE genes, and Mt2, a Zn-induced gene, were measured in ileum biopsies by RT-qPCR.",
    "ncbi_link": "Mt2: 17750
Stat1: 20846
Zbp1: 58203"
  },
  {
    "caption": "(A) C57BL/6J mice received 25 mM ZnSO4 or control water for 7 days. Mice were injected i.p. with 100, 200 or 500 µg dexamethasone (Dex, rapidexon), solved in sterile PBS, 30 min before a 50 µg TNF/20 g bodyweight i.p. challenge. STAT1+/+ and STAT1-/- mice were challenged with equal TNF dose, as controls. No mice died later than 120 h after TNF injection. Data show combined results of 2 experiments.",
    "ncbi_link": "STAT1: 20846"
  },
  {
    "caption": "Mice (N=4 per group) treated as in (A) and 6h after challenge, ileum was taken and RT-qPCR performed to study gene expression of cell death ISRE genes Mlkl and Zbp1",
    "ncbi_link": "Mlkl: 74568
Zbp1: 58203"
  },
  {
    "caption": "Mice (N=4 per group) treated as in (A) and 6h after challenge, ileum was taken and RT-qPCR performed to study gene expression of cell death ISRE genes Stat1.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "B. HEK293 cells expressing NSUN3-HisPrcFLAG (NSUN3) or the HisPrcFLAG-tag alone (FLAG) were either not crosslinked (-), UV crosslinked (UV) or treated with 5-azacytidine (5-AzaC). The protein-RNA complexes were affinity purified and the bound RNA was trimmed, end-labelled with 32P phosphate and ligated to linkers. Protein-RNA complexes were separated by SDS-PAGE, transferred to nitrocellulose and exposed to an X-ray film.",
    "ncbi_link": "NSUN3: 63899"
  },
  {
    "caption": "G. 5-AzaC crosslinking was performed and RNA associated with wildtype NSUN3, the catalytically inactive NSUN3 mutant (C265A) or the FLAG tag alone was isolated as described in (B). The RNA analysed by northern blot using probes against the mt-tRNAMet, mt-tRNAPro and mt-tRNAGlu. Inputs (0.1%) are shown on the left and eluates (50%) on the right.",
    "ncbi_link": "NSUN3: 63899"
  },
  {
    "caption": "A. In vitro methylation reactions were performed using recombinant His14-MBP-NSUN3 (NSUN3) or the catalytically inactive mutant His14-MBP-NSUN3-C265A (C265A), 3H-labelled S-adenosyl methionine as a methyl group donor and in vitro transcribed mt-tRNAMet, mt-tRNAPro and mt-tRNAGlu. The RNA was then separated on a denaturing polyacrylamide gel, stained with ethidium bromide (EtBr) to indicate inputs and exposed to an X-ray film to analyse methylation (3H-Me).",
    "ncbi_link": "NSUN3: 63899"
  },
  {
    "caption": "B. The distribution of Illumina sequence reads along the mt-tRNAMet sequence obtained from CRAC experiments with NSUN3 after UV (light grey) or 5-AzaC crosslinking (dark grey) is given as reads per million mapped reads. The position of the anticodon is indicated by a bar.",
    "ncbi_link": "NSUN3: 63899"
  },
  {
    "caption": "B. HEK293 cells expressing ABH1-HisPrcFLAG (ABH1) or the HisPrcFLAG-tag alone (FLAG) were UV crosslinked (UV) and protein-RNA complexes were affinity purified. Co-precipitated RNA was isolated and analysis by northern blot using probes against the mt-tRNAMet, mt-tRNAPro and mt-tRNAGlu. Inputs (0.1%) are shown on the left and eluates (50%) on the right.",
    "ncbi_link": "ABH1: 8846"
  },
  {
    "caption": "A. In vitro transcribed mt-tRNAMet was methylated at C34 using recombinant NSUN3 and 3H-labelled S-adenosyl methionine as a methyl group donor. Radiolabelled mt-tRNAMet was re-extracted and then subjected to oxidation assays without protein (-), with maltose binding protein (MBP), with the dioxygenase FTO or using wildtype (ABH1) or mutant (R338A, D233A) His14-MBP-ABH1. Besides ABH1 controls lacking a-ketoglutarate (KG) or Fe2+ ions, all samples contained a-ketoglutarate and Fe2+ ions. After oxidation, RNA was precipitated and tritium released upon oxidation of radiolabelled mt-tRNAMet was quantified in the supernatant and counts per minute (CPM) are shown for experiments performed in triplicate with error bars indicating ± SD (upper panel). Pelleted RNA was separated on a denaturing polyacrylamide gel and exposed to an X-ray film to analyse the tritium retained (3H-Me).",
    "ncbi_link": "ABH1: 8846"
  },
  {
    "caption": "A. HeLa cells were transfected with two different siRNAs against NSUN3 (siNSUN3_1, siNSUN3_2), ABH1 (siABH1_1, siABH1_2) or with nontarget (siNT) siRNA and the knockdown efficiency was analysed by quantitative PCR. The relative abundance of the NSUN3 or ABH1 mRNA was normalized to GAPDH levels. Data are presented as mean ± SD.",
    "ncbi_link": "GAPDH: 
ABH1: 8846
NSUN3: 63899"
  },
  {
    "caption": "D. RNA from wild-type HeLa cells and cells treated with siRNAs against NSUN3 or ABH1 (as in A) was either first reduced with NaBH4 or directly treated with bisulfite. After deamination and desulfonation, mt-tRNAMetRNAs were reverse transcribed, amplified, cloned and sequenced. The proportions of thymine (grey) generated by bisulfite-conversion or non-converted cytosine (black) at position 34 of mt-tRNAMet are shown. Note that for sequences from non-reduced samples, thymine can originate from unmodified or f5C-containing mt-tRNAMet, while in reduced samples it originates from unmodified cytosine.",
    "ncbi_link": "ABH1: 8846
NSUN3: 63899"
  },
  {
    "caption": "A. HeLa cells were treated with non-target siRNAs (siNT) or those targeting NSUN3 (siNSUN3_1 or siNSUN3_2) or ABH1 (siABH1_1 or siABH1_2) for 72 h before labelling of mitochondrial translation products with [35S]methionine. Protein samples were separated by SDS-PAGE then transferred to a membrane. Labelled proteins were detected using a phosphorimager and the levels of tubulin were determined by western blotting using an antibody against the endogenous protein for normalisation.B. Mitochondrially-translated proteins that could be clearly detected were quantified in three independent experiments and the results are shown graphically as mean ± SD.",
    "ncbi_link": "ABH1: 8846
NSUN3: 63899"
  },
  {
    "caption": "A) Ventral nests expansion at 0 min (onset); 245 min, when ventral and spiracle nests fuse; 515 min, when intersegment nests fuse; and 750 min, when most LECs are gone. We employed for these analyses the following stock: w; If/CyO; ZCL2207::hh-DsRed/MKRS. The green signal corresponds to ZCL2207 (Septate junction GFP marker) outlining all apical cell membranes and the red signal to nuclei from the posterior compartment expressing RFP under the control of the hedgehog promoter. Arrows point to the spiracular and ventral nests on the top panel and to the junction between these two nests in the second panel. Images of confocal sections have been rotated to maintain consistent alignment of the dorso-ventral axis (dorsal is up). The outlines of the confocal images are marked with a yellow dotted line. Scale bar = 40 µm.",
    "ncbi_link": "DsRed: 
MKRS: 
ZCL2207: 48971
hh: 42737
If: 32661"
  },
  {
    "caption": "A) Density power radial kymograph of a representative time-lapse movie of the nests expansion process after blocking histoblasts proliferation by overexpressing Dacapo. Each horizontal line displays at each time point (left scale) the mean of the power value at every distance (bottom scale) to the nest-LECs border (vertical black line). Each phase is represented in a colored background with three different densities of purple. Power values color scale is on the right.",
    "ncbi_link": "Dacapo: 36001"
  },
  {
    "caption": "B) Comparison of the means and standard deviations of the density power radial kymographs in phase 3 for Dacapo overexpressing nests (green) and wild type (purple).",
    "ncbi_link": "Dacapo: 36001"
  },
  {
    "caption": "D) Comparison of the means and standard deviations of the surface stress radial kymographs in phase 3 for Dacapo overexpressing nests (green) and wild type (brown).",
    "ncbi_link": "Dacapo: 36001"
  },
  {
    "caption": "E) Density power radial kymograph of a representative time-lapse movie after blocking LECs delamination by overexpressing P35. Power values color scale is on the right.",
    "ncbi_link": "P35: 40451"
  },
  {
    "caption": "F) Comparison of the means and standard deviations of the density power radial kymographs in phase 3 for P35 overexpressing LECs (green) and wild type (purple).",
    "ncbi_link": "P35: 40451"
  },
  {
    "caption": "H) Comparison of the means and standard deviations of the surface stress radial kymograph in phase 3 for P35 overexpressing LECs (green) and wild type (brown).",
    "ncbi_link": "P35: 40451"
  },
  {
    "caption": "A) Laser microsurgery was performed at the different sides of the ventral nests during phase 2 (300 minutes) in parallel cuts [in the LEC tissue at 40 µm of the nests/LEC border (cyan) and within the nests at 10 µm (red) and 40 µm (green) of the edge]. Myo-GFP transgenic pupae were used to visualize the cortex displacements. This example illustrates at the anterior edge the laser cuts positions. Scale bar = 15 µm.",
    "ncbi_link": "GFP: 
Myo: 43587"
  },
  {
    "caption": "E) Comparison of the mean laser recoil velocities in phase 3 for Dacapo overexpressing nests (green) with wild type (blue) at different distances (-40 - n = 16, -10 - n =22, +40 - n = 14) Error bars represent Standard Deviations.",
    "ncbi_link": "Dacapo: 36001"
  },
  {
    "caption": "F) Comparison of the mean laser recoil velocities in phase 3 for P35 overexpressing nests (green) with wild type (blue) at different distances (-40 - n = 17, -10 - n = 20, +40 - n = 15) Error bars represent Standard Deviations.",
    "ncbi_link": "P35: 40451"
  },
  {
    "caption": "A. (Top) USP44 transcript levels across CD4+ T cell populations. Suspension of the lymph node and spleen cells of 6-8 week old female C57BL/6 mice (n= 5 experiments) were obtained, and naïve (CD62Lhigh/CD25-) CD4+ T cells and nTregs (CD4+/CD25high) were obtained by FACS. The indicated effector T cell populations were generated by activating 1x10^6 naïve CD4+ T precursors with anti-CD3 and anti-CD28 antibodies (1 and 4 ug/ml, respectively) for 4 days under the indicated in vitro skewing conditions (described in the Methods section). After harvesting RNA by Trizol reagent and generating cDNA, the Usp44 mRNA levels expressed by the resulting Teff and iTreg, as well as freshly isolated nTreg cells were determined by qRT-PCR. (Bottom) Suspension of lymph node and spleen cells of 6-8 week old female C57BL/6 mice were obtained, and naïve (CD62LhighCD25-) CD4+ T cells and nTregs (CD4+/CD25high) were sorted by FACS. iTregs were generated by activating 1x10^6 naïve CD4+ T cells with anti-CD3 and anti-CD28 antibodies (1 and 4 ug/ml, respectively) for 4 days in the presence of IL-2 (100u/ml) and TGF-β (5ng/ml) before the cells were harvested for SDS-PAGE. Panels A and B depict the mean mRNA expression normalized to the housekeeping gene GAPDH.",
    "ncbi_link": "GAPDH: 
USP44: 327799
Usp44: 327799"
  },
  {
    "caption": "B. Naïve murine CD4+ T cells were obtained and differentiated into the iTreg lineage as in A. Expression levels of Usp44 and Foxp3 mRNA were assessed daily over time by qRT-PCR.",
    "ncbi_link": "Foxp3: 20371
Usp44: 327799"
  },
  {
    "caption": "A. HEK293T cells were transfected with MYC-FOXP3 and FLAG-USP44 encoding expression constructs using Polyethylenimine. 48hrs post-transfection, cells were harvested, lysed, and anti-FLAG or anti-MYC antibody coated beads were used to immunoprecipitate the given labeled protein along with its binding partner. Co-IP'ed proteins were subjected to SDS PAGE followed by immunoblot analysis. Antibodies recognizing FLAG or MYC tags were used to probe for USP44 and FOXP3, respectively.",
    "ncbi_link": "FLAG: 
MYC: 
FOXP3: 50943
USP44: 84101"
  },
  {
    "caption": "D. Naïve murine CD4+ T cells were isolated by FACS from lymph node and spleen cell suspension of USP44fl/fl CD4Cre+ mice and that of their wild type littermates (USP44fl/fl CD4Cre- mice; n=2-3/group/experiment). iTreg cells were generated from these mice as described for Fig. 1 before incubation on a microscope slide pre-coated with poly-L lysine for 1h. Adhered cells were then fixed by PFA for 0.5 followed by blocking with 1% BSA for 1h, then incubation with the specified antibodies. Representative confocal microscopy images (40X) were visualized for endogenous USP44 (red) and FOXP3 Baxter et al(). DAPI was used to visualize cell nuclei (blue); scale bar 50μm.",
    "ncbi_link": "CD4: 12504
Cre: 2777477
USP44: 327799"
  },
  {
    "caption": "A. HEK293T cells were transfected with expression constructs encoding MYC-FOXP3, His-Ubiquitin, and either a wild type or catalytically inactive (C282S, "cs") version of USP44 tagged with FLAG. Transfected cells were treated with 20 μM MG132 for 4 hrs and subsequently harvested for cell lysis. Pull-down of His-labeled proteins using Ni-NTA beads allowed recovery of ubiquitinated FOXP3 species that were then visualized by immunobot probing with antibodies specific for MYC.",
    "ncbi_link": "FLAG: 
His: 
MYC: 
FOXP3: 50943
USP44: 84101"
  },
  {
    "caption": "B. Effect of USP44 knock down on FOXP3 ubiquitination. Two distinct shRNA lentiviral constructs each containing a G418 resistance cassette were delivered into HEK293T cells. After selected for 7d, cells were transfected with MYC-FOXP3 and His-Ubiquitin, then treated with 20 μM MG132 for 4 hrs before harvest and lysis. Ubiquitinated FOXP3 proteins were visualized as in A.",
    "ncbi_link": "His: 
MYC: 
FOXP3: 50943
USP44: 84101"
  },
  {
    "caption": "C. Levels of polyubiquitinated FOXP3 in the presence or absence of USP44. As in Fig 2b, murine iTregs were generated from naïve CD4+ precursors isolated from wild type and mice globally deficient in USP44-/- mice (n=3/group/experiment). Ubiquitinated proteins were extracted from iTreg lysates with anti-ubiquitin antibodies (anti-Ubi) prior to resolution by SDS PAGE and immunoblot analysis, probing for FOXP3.",
    "ncbi_link": "USP44: 327799"
  },
  {
    "caption": "D, E. HEK293T cells were transfected with plasmids encoding MYC-FOXP3, FLAG-USP44 (either wild type USP44, "wt" or the C282S mutant). These cells were subsequently treated with cycloheximide (CHX; 5μg/ml) for the indicated time points before harvested and cell lysis. FOXP3 levels and the relative turnover rate of this factor was determined by immunoblotting analysis with anti-MYC antibodies.",
    "ncbi_link": "FLAG: 
MYC: 
FOXP3: 50943
USP44: 84101"
  },
  {
    "caption": "F, USP44 knock down in human Tregs. Naïve CD4+ T cells (CD4+CD25-CD45RA+) were isolated from the peripheral blood of healthy donors by FACS, and iTreg were generated after 7 days of in vitro skewing conditions. As in Fig. 3b, shRNA constructs targeting USP44 were delivered by lentivirus. Here human iTregs received either shCK (control), or one of two different shUSP44 constructs. Endogenous FOXP3 and USP44 protein levels were visualized by immunoblot (F)",
    "ncbi_link": "USP44: 84101"
  },
  {
    "caption": "G. USP44 knock down in human Tregs. Naïve CD4+ T cells (CD4+CD25-CD45RA+) were isolated from the peripheral blood of healthy donors by FACS, and iTreg were generated after 7 days of in vitro skewing conditions. As in Fig. 3b, shRNA constructs targeting USP44 were delivered by lentivirus. Here human iTregs received either shCK (control), or one of two different shUSP44 constructs. FOXP3 expression was assessed by intracellular staining followed by flow cytometry (G).",
    "ncbi_link": "USP44: 84101"
  },
  {
    "caption": "H. Murine naïve CD4 T cells (CD62L+/CD25-/CD4+) from WT and USP44-/- mice (n=2-3/group/experiment) were FACS purified and activated in vitro for four days by CD3/CD28 cross-linking antibodies (1ug and 4ug/ml, respectively) in the presence of 100 U/ml IL-2 and the indicated dose of TGF-β. Down-regulation of FOXP3 was observed in USP44-/- mice by intracellular immunostaining and flow cytometry.",
    "ncbi_link": "USP44: 327799"
  },
  {
    "caption": "A. Reciprocal Co-IP of USP44 and USP7. HEK293T cells were transfected with constructs encoding MYC-USP44 and FLAG-USP7. These cells were lysed and pertinent factors were immunoprecipitated using either anti-FLAG or anti-MYC. Pulled-down proteins were observed by immunoblot analysis using either anti-MYC or anti-FLAG antibodies.",
    "ncbi_link": "FLAG: 
MYC: 
USP44: 84101
USP7: 7874"
  },
  {
    "caption": "B. Effect of USP44 on USP7 levels. HEK293T cells were transfected with MYC-FOXP3. Cells also received combinations of FLAG-USP7 and varying doses of pLVX-USP44 encoding plasmids. FOXP3 was immunoprecipitated using anti-MYC, and immunoblots were analyzed using anti-FLAG, anti-USP44 or anti-MYC antibodies.",
    "ncbi_link": "FLAG: 
MYC: 
FOXP3: 50943
USP44: 84101
USP7: 7874"
  },
  {
    "caption": "C. Effect of USP44 and USP7 coexpression on FOXP3 ubiquitination. HEK293T cells were transfected with plasmids encoding MYC-FOXP3, either FLAG-USP44 or FLAG-USP7 or both, His-ubiquitin. Cells were treated with 20 μM MG132 for 4 hrs before being harvested, lysed, and incubated on Ni-NTA beads to pull down ubiquitinated FOXP3, which was visualized by immunoblotting using antibodies specific for MYC.",
    "ncbi_link": "FLAG: 
His: 
MYC: 
FOXP3: 50943
USP44: 84101
USP7: 7874"
  },
  {
    "caption": "D. (left panel) iTreg were polarized from human naïve CD4+ T cells over 7 days (n=3 donors /experiment) receiving control (shCK), or shRNA knockdown constructs targeting USP44 (shUSP44-1, -2), or USP7 (shUSP7-1, -2), or both shRNA constructs. Freshly isolated nTregs were treated with either control or shRNA constructs. After transduction with lentivirus for 48 hours, cells were harvested and run SDS-PAGE gels. Protein levels were visualized by immunoblotting using antibodies specific for FOXP3, USP44, USP7 and GAPDH. Shown are representative findings from 3 independent experiments (biological replicates).",
    "ncbi_link": "USP44: 84101
USP7: 7874"
  },
  {
    "caption": "A. Jurkat T cells were transfected with the indicated combinations and relative doses of expression constructs encoding MYC-FOXP3, FLAG-USP44 along with an IL-2 promoter-driven firefly luciferase reporter. After 8 hours stimulation with PMA/Inomycin, cells were lysed and luciferase activity, which was observed and normalized to renilla luciferase activity.",
    "ncbi_link": "FLAG: 
luciferase: 
MYC: 
FOXP3: 50943
IL-2: 3558
USP44: 84101"
  },
  {
    "caption": "B. Tregs (CD4+/CD25High) were recovered from the lymph nodes and spleens of wild type C57BL/6 (WT) and USP44-/- mice by FACS purification. Cells were activated with anti-CD3/CD28 agonist antibodies overnight, and RNA was isolated, and cDNA was generated from these samples for the measurement of several signature Treg-associated transcripts by qRT-PCR. The relative expression level of these by WT and KO-derived Tregs is shown.",
    "ncbi_link": "USP44: 327799"
  },
  {
    "caption": "C, D. Analysis of the in vitro suppressive function of Tregs isolated from WT mice or age- and sex-matched USP44-/- mice (n=3/group/experiment). Tregs were mixed with CFSE-labeled responder naïve T cells from CD45.1+ C57BL/6 mice (n=3/experiment) for three days. CFSE dilution in CD45.1+ T cells was observed by flow cytometry and the percent suppression of responder cell proliferation by the co-cultured Tregs was determined.",
    "ncbi_link": "USP44: 327799"
  },
  {
    "caption": "A. Colitis was induced by intravenous coinjection of CD4+CD25-CD62Lhigh T cells and congenically distinct (CD45.2) CD4+CD25high Treg cells into Rag2-/- mice (n=8/group; 1x106 and 2x105 cells per Rag2-/- recipient, respectively). Changes in body weight over time were monitored and are expressed as a percentage of the original weight.",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "B. Representative photomicrographs of the distal colon of Rag2-/- mice after T cell transfer. 10 weeks after transfer, mice were euthanized, and colons were harvested, fixed in 10% buffered formalin, and processed for standard H&E staining prior to histological analysis. (i)- (iv) present bright-field micrographs (100x).",
    "ncbi_link": "Rag2: 19374"
  },
  {
    "caption": "E. Expression of FOXP3 protein and mRNA by adoptively transferred Tregs. Mesenteric lymph nodes were excised from the recipients of WT and USP44-/- Tregs in A. FOXP3 protein was detected by intracellular immunostaining and flow cytometry (left). Shown are events within the gate for transferred Tregs (CD4+/CD45.1+). Transferred Tregs were also recovered from mesenteric lymph node cell suspensions by staining for the congenic marker and CD4 followed by FACS, and Foxp3 mRNA was measured in these recovered Tregs by RT-PCR (right).",
    "ncbi_link": "Foxp3: 20371
USP44: 327799"
  },
  {
    "caption": "MC38 colon carcinoma, B16F10 melanoma cell lines were s.c. injected into the shaved flanks of Usp44fl/flFoxp3Cre+ mice and their wild type (Usp44fl/flFoxp3Cre-) littermates (1x105 cells/mouse; n=5-9 mice/group). Tumor dimensions were measured every 2 days, and changes in the mean tumor volume over time were observed (lower panels). Upper panels depict representative photographs of excised tumors.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Usp44: 327799"
  },
  {
    "caption": "EL4 thymoma cell lines were s.c. injected into the shaved flanks of Usp44fl/flFoxp3Cre+ mice and their wild type (Usp44fl/flFoxp3Cre-) littermates (1x105 cells/mouse; n=5-9 mice/group). Tumor dimensions were measured every 2 days, and changes in the mean tumor volume over time were observed (lower panels). Upper panels depict representative photographs of excised tumors.",
    "ncbi_link": "Cre: 2777477
Foxp3: 20371
Usp44: 327799"
  },
  {
    "caption": "(A) Hep3B hepatocytes were treated with nontargeting control siRNA (siNT) or siRNA targeting Dyn2 (siDyn2), followed by re-expression of either vector alone, or GFP-tagged versions of Dyn2, loaded with 150 µM oleate overnight and starved for 48 h in medium containing 0.1% FBS. LDs were visualized by immunofluorescence using Oil Red O staining. Cell boundaries are outlined and those cells re-expressing GFP, GFP-wtDyn2, or GFP--K44A are denoted with asterisks. Bars, 20 µM. (B) Representative blot showing the efficiency of the Dyn2 knockdown in these cells. (C and D) Quantitation of the average LD number and area (in pixels2) per cell from three independent experiments. The data are represented as mean ± SE. *, P ≤ 0.05; **, P ≤ 0.01. NS, not significant.",
    "ncbi_link": "Dyn2: 25751
Dyn2: 1785"
  },
  {
    "caption": "HuH-7 (A) and Hep3B (B) hepatocytes were loaded with 150 µM oleate overnight and starved for 48 h in medium containing 0.1% FBS in the presence of Dyn2 inhibitors or DMSO as indicated. Representative images of inhibitor-treated and control cells (stained with Oil Red O) are shown in A and B together with the quantitation of the average LD area per cell from three independent experiments. Pharmacological inhibitors used were: Dynasore (inhibits Dyn2 GTPase activity), MiTMAB (targets PH domain and interferes with membrane binding), Dynole 34-2 (allosteric GTPase inhibitor), and Dynole 31-2 (negative control for Dynole 34-2). Bars, 20 µM.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(C) Representative images from control and Dyn2 knockout MEFs after an overnight lipid loading with 400 µM Dyn2 for 17 h. Knockout of Dyn2 was induced by treatment with 2 µM 4-hydroxy-tamoxifen for 7 d and was confirmed by immunostaining of endogenous Dyn2 (top row) and by immunoblot (D). Bars, 20 µM. (E and F) Average LD number (E) and area (F) per cell from five independent experiments. All data are represented as mean ± SE. *, P ≤ 0.05; **, P ≤ 0.01.",
    "ncbi_link": "Dyn2: 13430"
  },
  {
    "caption": "Hep3B cells treated with either a nontargeting control siRNA (A and B, siNT) or an siRNA targeting human Dyn2 (C and D, siDyn2) were fixed and co-stained with antibodies specific for LAMP1 (red) and LC3 (green). After Dyn2 knockdown, a juxtanuclear aggregation and enlargement of the LAMP1-positive compartment is observed (C and D, arrows). Increased labeling of LC3 is also detectable after knockdown of Dyn2.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(E) Western blotting of Hep3B lysates after a 3-d treatment with either the control or Dyn2-targeted siRNA and further treatment with or without 50 µM leupeptin. Densitometry-based analysis of six independent experiments is shown at the bottom of the figure.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "Dyn2 knockdown results in the formation of enlarged autophagic structures. (A-D) Transmission electron micrographs (TEMs) of oleate-loaded Hep3B hepatocytes treated with nontargeting control (siNT) or Dyn2 (siDyn2) siRNA for 72 h. Bars: (A and B) 2 µm; (A′ and B′) 1 µm; (C and D) 0.5 µm. Insets in A and B show fluorescent micrographs of LAMP1-stained cells (bars, 10 µM). Control cells (A) contain an abundance of small (<1 µm) electron-dense lysosomes and autolysosomes (arrowheads). Under conditions in which Dyn2 expression is suppressed (B-D), far fewer small lysosomes are observed. Instead, the cells are populated by larger autolysosomes (≥1 µm) with aberrant morphologies and containing putative LDs (*). (E) Quantitative measure of autolysosomal size from cells in which Dyn2 was knocked down as compared with control cells. Values represent the fold-increase in the number of autophagic structures of a given diameter (measured in microns) observed over siNT-treated control cells. Data were obtained from a single experiment with n = 6 cells examined by electron microscopy from each condition.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "Hep3B cells treated with either a nontargeting control siRNA (A and B, siNT) or an siRNA targeting human Dyn2 (C and D, siDyn2) were fixed and stained with an antibody specific for LAMP1 after a 24-h starvation period in media containing 0.1% FBS. Control cells displayed normal lysosomal compartments, with LAMP1-stained structures dispersed throughout the cytosol, some containing short reformation tubules (B′). After Dyn2 knockdown, many cells contained enlarged autolysosomes with a noticeable increase in persistent and lengthy reformation tubules emanating from LAMP1-positive compartments (C′ and D′). Bars: (A-D) 20 µM; (A′ and B′) 5 µM; (C′ and D′) 10 µM. (E and F) Measurements of the length (E) and distribution (F) of LAMP1-stained ALR tubules in control (siNT) and siDyn2-treated cells. Data represent the mean derived from measurements of tubules in a minimum of 40 cells for each experimental group over 6 independent experiments. Error bars represent SE; *, P ≤ 0.05; **, P ≤ 0.01.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(G) TEM of siDyn2-treated Hep3B hepatocyte exhibiting enlarged autolysosomal structures with extensive tubulation (arrows). Bar, 2 µm. (G′) Inset showing enlargement of autolysosomal tubule (arrows). Bar, 1 µm. (H) Tubulating autolysosome with engulfed lipid droplet. Bar, 0.5 µm.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "Acute inhibition of Dyn2 reversibly disrupts autophagic lysosomal reformation (ALR) and lysosomal tubule scission. (A-D) Still frames from time-lapse movies of Hep3B cells expressing LAMP1-mCherry. Cells were starved for 2 h in HBSS and subsequently treated for 30 min with either DMSO (A and B) or 40 µM Dynasore (C and D), which induced extensive tubulation of LAMP1-positive compartments. Bars (A-D): 20 µM; (A′-B′) 2 µM; (C′-D′) 10 µM. (E-G) To demonstrate the reversibility of this tubulation, Dynasore-treated cells were washed extensively with drug-free media containing 10% FBS and monitored by time-lapse microscopy for 45 min. Frequently, after drug washout, LAMP1-positive tubules exhibited noticeable varicosities (E and F, arrows; bars, 10 µM) along their length. These sites are suggestive of areas of scission and resumed budding of nascent protolysosomes from the reformation tubules (G; bars, 10 µM). (H) Tubules from cells undergoing drug washout were quantified by tracing their lengths at the beginning and end of these movies. Still frames from a representative movie show tubule content at t = 10 and 45 min after drug washout. Bars, 20 µM. (I) Analysis of five independent movies showed an average decrease in total tubulation of ∼50% after drug washout. Data represent the average relative change in total tubule length between the first and last frames of the time-lapse movies. Error bars represent SE; *, P < 0.05.",
    "ncbi_link": "Dyn2: 1785"
  },
  {
    "caption": "(C) Co-immunoprecipitation between VP30 and the indicated PPxPxY containing host factors. Empty expression plasmid (Vector) or FLAG-tagged host protein expression plasmids were co-transfected with an HA-VP30 expression plasmid in HEK293T  cells. An anti-FLAG immunoprecipitation (IP: Anti-FLAG) was performed. Western blots of IP  and whole cell lysates (WCL) are shown. Anti-β-tubulin was used as a loading control for the WCLs.",
    "ncbi_link": "HA: 
VP30: 911826"
  },
  {
    "caption": "(D) Cells were transfected with empty vector or HA-VP30 expression plasmid and IPs were performed with anti-HA antibody (IP: Anti-HA). Western blotting with anti-HA tag or antibodies to the indicated host proteins was performed on  IP  and on whole cell lysates (WCL).",
    "ncbi_link": "HA: 
VP30: 911826"
  },
  {
    "caption": "(A) Co-immunoprecipitation experiment demonstrating that NP interferes with VP30-PPxPxY  binding. VP30 was co-expressed with the indicated HA-tagged PPxPxY proteins and either empty vector (-) or increasing amounts of FLAG-tagged  NP expression plasmid.  IPs were performed with anti-HA antibodies followed by Western blots  of IPs or WCL by using anti-HA, anti-FLAG  and anti-VP30  antibodies.",
    "ncbi_link": "FLAG: 
NP: 911830"
  },
  {
    "caption": "(C) Co-immunoprecipitations between VP30 and the indicated host proteins upon titration of RBBP6. VP30 was co-expressed with FLAG-tagged PPxPxY containing host proteins and either a 5-fold or 10-fold excess of RBBP6 plasmid. IP was performed using anti-FLAG beads followed by Western blotting using the indicated antibodies.",
    "ncbi_link": "RBBP6: 5930"
  },
  {
    "caption": "(D) Minigenome (MG) activity upon titration of plasmids encoding GFP  fused to wildtype or single point mutant-RBBP6 peptides. GFP alone or GFP-RBBP6  peptide plasmids were transfected at 12.5 and 25 ng amounts along with the plasmids of the  MG system. The data represent the mean ± S.D. from one representative experiment in which each transfection condition was performed in triplicate (n=3). The experiment was reproduced in two additional, independent experiments (see Appendix Figure S2). Statistical significance was calculated using ANOVA with Tukey's multiple comparisons test. ****p<0.00005; ***p<0.0005",
    "ncbi_link": "RBBP6: 5930"
  },
  {
    "caption": "(C) MG activity upon knockdown of host genes.  HEK293T cells were transfected with scrambled siRNA or siRNA targeting  RBBP6, hnRNP L, hnRNPUL1 or PEG10. Twenty-four hours post-transfection, cells were transfected with  MG assay  plasmids including VP30 at 12.5 and 25ng doses. Data information: , the data represent the mean ± S.D. from one representative experiment in which each transfection condition was performed in triplicate (n=3). The experiment was reproduced in two additional, independent experiments Statistical significance was calculated using ANOVA with Tukey's multiple comparisons test. ****p<0.00005; ***p<0.0005, **p<0.005, *p<0.05.",
    "ncbi_link": "hnRNP L: 3191
hnRNPUL1: 11100
PEG10: 23089
RBBP6: 5930"
  },
  {
    "caption": "(A)  HeLa cells were transfected with scrambled siRNA (SCR si) or siRNAs targeting  hnRNP L, hnRNPUL1  or PEG10, 48 h post-transfection, cells were challenged with EBOV-EGFP at an MOI of 0.5. 24 h post-infection, cells were fixed, stained  for nuclei with Hoechst dye and imaged. Scale bar is 200 µm.The graph (right) depicts relative number of infected cells as determined by calculating the ratio of  number of infected cells to  nuclei  and shown relative to SCR siRNA. The data shows a representative result of two independent experiments with the mean ± S.D. calculated from three independently treated wells. Statistical significance was calculated relative to the values obtained in SCR siRNA-treated cells using ANOVA with Dunnett's multiple comparisons test. ***p<0.0001, ***p<0.001, **p<0.01",
    "ncbi_link": "hnRNP L: 3191
hnRNPUL1: 11100
PEG10: 23089"
  },
  {
    "caption": "(C) Immunoblots to assess VP30 and pVP30 levels in lysates from MG assay upon knockdown of RBBP6, hnRNP L or hnRNPUL1.",
    "ncbi_link": "hnRNP L: 3191
hnRNPUL1: 11100
RBBP6: 5930"
  },
  {
    "caption": "(D) Immunoblots to assess the levels of VP30, pVP30  and NP in EBOV infected lysates upon knockdown of NPC1 or  RBBP6. HeLa cells were mock transfected or transfected with siRNA targeting NPC1 or RBBP6. 48 h post-transfection cells were infected with  EBOV  at MOI=0.1. At 24 h post-infection, cells were lysed in TRIzol. Protein was extracted from the TRIzol  reagent and analyzed by Western blotting to determine levels of VP30, pSer29  VP30 and  NP.",
    "ncbi_link": "NPC1: 4864
RBBP6: 5930"
  },
  {
    "caption": "(E) Western blots detecting pVP30,  VP30  and NP  levels in EBOV infected HeLa cells upon hnRNP L, hnRNPUL1 or PEG10 knockdown.",
    "ncbi_link": "hnRNP L: 3191
hnRNPUL1: 11100
PEG10: 23089"
  },
  {
    "caption": "LPS-primed WT and Vdr-/- BMDMs  were infected with 50 MOI S. Typhimurium  for 2 h. Culture supernatants  (SN) and cell lysates(Lysate) were collected and immunoblotted  with the indicated antibodies（A）.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT and Vdr-/- BMDMs  were infected with 50 MOI S. Typhimurium for 2 h. Culture supernatants (SN) were collected and (B-E) IL-1β  secretion(B), IL-18  secretion (C) and TNF-ɑ secretion (D) and LDH  release(E) in supernatants. Data are shown as means ± SEM; determined by Student's t-test; *, P < 0.05; **, P < 0.01 In each panel, data are representative of at least three independent experiments.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT and Vdr-/- BMDMs  were infected with 50 MOI S. Typhimurium for 2 h. (F) HBVLV-Vdr  expression in Vdr-/- BMDMs  by lentivirus-mediated transduction primed with LPS  and infected with 50 MOI S. Typhimurium for 2 h, cell lysates, and culture supernatants  (SN) were collected and immunoblotted  with the indicated antibodies.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "(G) LPS-primed WT and Vdr-/- BMDMs  were treated with 1 µg/ml FLIC  (LFn-Flagellin  and PA) or PrgJ  （1 µg/ml LFn- PrgJ  and PA）for 1 h, total mixtures( culture supernatants  and cell lysates) were collected and immunoblotted  with the indicated antibodies.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "(H) LPS-primed WT, Vdr-/-, NLRC4-/- and Vdr-/-NLRC4-/- BMDMs  were treated with FLIC  for 1 h, Culture supernatants  (SN) and cell lysates  were collected and immunoblotted  with the indicated antibodies.",
    "ncbi_link": "NLRC4: 268973
Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT, Vdr-/-, NLRC4-/- and Vdr-/-NLRC4-/- BMDMs  were treated with FLIC  for 1 h, Culture supernatants (SN) were collected and (I-L) IL-1β secretion(I),  IL-18 secretion (J) and TNF-ɑ secretion (K) and LDH  release(L) in supernatants. Data are shown as means ± SEM; determined by Student's t-test; *, P < 0.05; **, P < 0.01 In each panel, data are representative of at least three independent experiments.",
    "ncbi_link": "NLRC4: 268973
Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT, Vdr-/-, NLRP3-/- and NLRP3-/- Vdr-/- BMDMs  were infected with different MOI (0,10,50) S. Typhimurium for 2 h.Culture supernatants  (SN) and Cell lysates were collected and immunoblotted   with the indicated antibodies(A).ELISA",
    "ncbi_link": "NLRP3: 216799
Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT, Vdr-/-, NLRP3-/- and NLRP3-/- Vdr-/- BMDMs  were infected with different MOI (0,10,50) S. Typhimurium for 2 h.Culture supernatants  (SN) were collected antibodies(A).ELISA  detected  TNF-ɑ(B)andIL-1β (C) in supernatants. Data information:n ≥ 3 biological replicates. Data are presented as the mean ± SEM; determined by Student's t-test ; **, P < 0.01.",
    "ncbi_link": "NLRP3: 216799
Vdr: 22337"
  },
  {
    "caption": "LPS-primed WT, Vdr-/-, NLRP3-/- and NLRP3-/- Vdr-/- BMDMs  were infected with S. Typhimurium Bacterial burden was detected in spleens(D), PCF(E), and blood  (F)of WT, Vdr-/-, NLRP3-/-, and NLRP3-/- Vdr-/- mice  24 h after S. Typhimurium infection. Data information:n ≥ 3 biological replicates. Data are presented as the mean ± SEM; determined by Student's t-test ; **, P < 0.01.",
    "ncbi_link": "NLRP3: 216799
Vdr: 22337"
  },
  {
    "caption": "A LPS-primed WT and Vdr-/- BMDMs  were infected with  S. Typhimurium at an MOI of 50 for 2 h. Endogenous ASC  specks (arrows) were represented and quantified by immunofluorescence  images. The data show representative results from three independent experiments: scale bar, 20 μm. Data are presented as the mean ± SEM; determined by Student's t-test ; ***,p < 0.001.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "B ASC oligomerization  induced by the indicated stimuli in WT and Vdr  −/− BMDMs  primed with LPS.",
    "ncbi_link": "Vdr: 22337"
  },
  {
    "caption": "(B-C) Flag-VDR  was co-expressed with Myc-NLRC4  in HEK293T  cells; proteins were immunoprecipitated  and analyzed by immunoblotting  with indicated antibodies. Whole-cell lysates were shown as the input. Data are representative of three independent experiments.",
    "ncbi_link": "Flag: 
Myc: 
NLRC4: 58484
VDR: 7421"
  },
  {
    "caption": "(E) WT or mutant NLRC4  (CARD, NACHT, or LRR (leucine-rich repeat)) and HA-VDR   were expressed in HEK293T  cells, immunoprecipitated, and analyzed by immunoblotting  with indicated antibodies.*no specific band. Data are representative of three independent experiments.",
    "ncbi_link": "HA: 
NLRC4: 58484
VDR: 7421"
  },
  {
    "caption": "(F) WT or mutant VDR  (DBD or LBD) and Myc-NLRC4  were expressed in HEK293T cells, immunoprecipitated, and analyzed by immunoblotting  with indicated antibodies. Data are representative of three independent experiments.",
    "ncbi_link": "Myc: 
NLRC4: 58484
VDR: 7421"
  },
  {
    "caption": "A-B HEK293T  cells were transfected with Flag-NLRC4, VDR, Myc-FLagellin, and HA-NAIP5  (A) or Flag-NLRC4, VDR, Myc- PrgJ  and HA-NAIP2(B) Samples were immunoprecipitated  with the anti-Flag  and analyzed by immunoblotting  with indicated antibodies.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
FLagellin: 1253480
NAIP2: 17948
NAIP5: 17951
NLRC4: 58484
PrgJ: 1254395
VDR: 7421"
  },
  {
    "caption": "HEK293T  cells were transfected with Flag-NLRC4, LBD-VDR, Myc-FLagellin, and HA-NAIP5  (C) or Flag-NLRC4, LBD-VDR, Myc-PrgJ, and HA-NAIP2  (D). Samples were immunoprecipitated  with the anti-Flag  and analyzed by immunoblotting  with indicated antibodies.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
FLagellin: 1253480
NAIP2: 17948
NAIP5: 17951
NLRC4: 58484
PrgJ: 1254395
VDR: 7421"
  },
  {
    "caption": "B VDR  or mutant VDR(K123A)and Myc-NLRC4  were expressed in HEK293T  cells, immunoprecipitated  with the anti-Flag  antibody, and analyzed by immunoblotting  with indicated antibodies.",
    "ncbi_link": "Myc: 
NLRC4: 58484
VDR: 22337"
  },
  {
    "caption": "C Transfected VDR  or mutant VDR(K123A) and Flag-NLRC4, Myc- PrgJ, and HA-NAIP2  in HEK293T  cells, immunoprecipitated  with the anti-HA  antibody, and analyzed by immunoblotting  with indicated antibodies.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
NAIP2: 17948
NLRC4: 58484
PrgJ: 1254395
VDR: 22337"
  },
  {
    "caption": "D Vdr-/- BMDMs  were infected with lentivirus, which expressed Vector(NC), VDR, and VDR-K123A, infected with  S. Typhimurium  at an MOI of 50 for 2 h, cell lysates(Lysate) and culture supernatants(SN) were collected and immunoblotted  with the indicated antibodies.",
    "ncbi_link": "Vdr: 22337
VDR: 7421"
  },
  {
    "caption": "(H) HA-tagged EBNA2 candidate phosphorylation mutants were expressed in DG75 B cells and tested for activation of an EBNA2/CBF1 responsive promoter reporter luciferase plasmid. Activation of the reporter gene is shown as relative response ratio normalized to Renilla luciferase activity and shown relative to wt activity.",
    "ncbi_link": "HA: 
luciferase: 
CBF1: 9541
EBNA2: 3783761"
  },
  {
    "caption": "(A) Flag-tagged active (PLK1) and kinase inactive PLK1 (K82M) were co-expressed with HA-EBNA2 wt, docking site mutant (S379A) and phosphorylation mutant (S457A/T465V) and tested for activation of an EBNA2/CBF1 responsive promoter reporter in DG75 cells. Activation of the reporter firefly luciferase gene is shown as relative response ratio normalized to Renilla luciferase activity and shown relative to EBNA2 wt activity.",
    "ncbi_link": "Flag: 
HA: 
luciferase: 
CBF1: 9541
EBNA2: 3783761
PLK1: 5347"
  },
  {
    "caption": "(E) Development of viral loads in blood of infected mice over a period of five weeks. Error bars indicate mean ± SEM. Number of biological replicates per group: EBNA2 WT EBV week 2 - 5: n = 8; EBNA2 S379A EBV week 2 - 5: n = 7; EBNA2 S457A T465V EBV week 2: n = 9, week 3: n = 8, week 4 and week 5: n = 7",
    "ncbi_link": "EBNA2: 3783761"
  },
  {
    "caption": "(F) Flow-cytometric analyses of CD8+/CD4+ T cell ratios in the blood of infected mice over a period of five weeks. : EBNA2 WT EBV week 0, 2, 4, 5: n = 13, week 3: n = 8 ; EBNA2 S379A week 0, 2, 4, 5: n = 11, week 3: n = 7 ; EBNA2 S457A T465V week 0, 2: n = 12, week 3: n = 7, week 4: n = 10, week 5: n = 9.",
    "ncbi_link": "EBNA2: 3783761"
  },
  {
    "caption": "Nuclear-to-cytoplasm chromatin blebbing in senescent cells associated with depletion of lamin B1. (A) Extrusion of GFP-H2B-positive chromatin fragment from nonmitotic RS nucleus. Confocal time-lapse microscopy of transiently transfected GFP-H2B-expressing cell, 60× original magnification, 150 nm optical section, time in mins. Bars: 10 µm; (insert) 2 µm.",
    "ncbi_link": "lamin B1: 4001"
  },
  {
    "caption": "(C) Down-regulation of lamin B1 and lamin B receptor (LBR) in RS cells, assayed by Western blot. See Materials and methods for time-course details.",
    "ncbi_link": "lamin B receptor: 3930
lamin B1: 4001"
  },
  {
    "caption": "(D) Depletion of lamin B1 from OIS cells, assayed by immunofluorescence. (E) A line-scan of lamin B1 fluorescence intensity along the arrows in D. Data shown are from a single representative experiment out of three repeats.",
    "ncbi_link": "lamin B1: 4001"
  },
  {
    "caption": ". (F) Depletion of lamin B1 in BRAFV600E-induced OIS melanocytes in vitro. Bars, 10 µm. (G) Quantitative immunofluorescence of lamin B1 in melanocytes from F. A representative experiment out of two repeats is shown. At least 150 randomly selected cells were assessed.",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "Senescent cells in vitro and in vivo contain reduced histone content. (A) Immunofluorescent confocal images of histone H3 in control or OIS cells (11 d after activation of ER-RASG12V). Yellow arrows indicate cells with most pronounced SAHF. (B) Quantitative immunofluorescence analysis of histone H3 in RS and OIS cells. Representative of two independent experiments.",
    "ncbi_link": "RAS: 3265"
  },
  {
    "caption": "Senescence-associated loss of histones is V-ATPase dependent. (A) Bafilomycin A1 (BafA1) blocks the loss of nuclearhistone H3content in cells undergoing OIS. BafA1 was added to cells at 50 nM on day 5 after RASG12V induction. Cells were harvested 24 h later, and stained for histone H3. Bars, 10 µm. (B) Quantitative histone H3immunofluorescence in cells from A. Single representative experiment out of three repeats.",
    "ncbi_link": "RAS: 3265"
  },
  {
    "caption": "(C) RASG12V-induced OIS cells were treated with BafA1 as described in A and then assessed for histones by Western blot. LC3 I/II has been used as a control for BafA1 activity. Lysates from 10,000 cells were loaded per well.",
    "ncbi_link": "RAS: 3265"
  },
  {
    "caption": "Morphology of wild-type (Tefm+/+) and Tefm homozygous knockout (Tefm-/-) embryos at embryonic day 8.5 (analyzed embryos, n= 43). Scale bar, 500 μm.",
    "ncbi_link": "Tefm: 68550"
  },
  {
    "caption": "Western blot analyses of the TEFM protein level in heart mitochondrial extracts from 8-week-old control (L/L) and tissue-specific Tefm knockout (Tefm knockout; L/L, cre) mice (n = 12 mice for each group). VDAC was used as loading control.",
    "ncbi_link": "cre: 2777477
Tefm: 68550"
  },
  {
    "caption": "Survival curve for control (L/L; n= 60) and Tefm knockout (L/L, cre; n= 22) mice.",
    "ncbi_link": "cre: 2777477
Tefm: 68550"
  },
  {
    "caption": "Heart weight to body weight ratio in 4- and 8-week-old control (L/L) and Tefm knockout mice (L/L, cre). At 4 weeks: L/L n= 22, L/L, cre n= 15; 8 weeks: L/L n= 41, L/L, cre n= 39.",
    "ncbi_link": "cre: 2777477
Tefm: 68550"
  },
  {
    "caption": "Transmission electron micrographs of heart tissue in 8-week-old control and Tefm knockout mice (n = 5 mice for each group). Scale bar, 2 μm (upper panel) and 1 μm (lower panel).",
    "ncbi_link": "Tefm: 68550"
  },
  {
    "caption": "Southern blot analyses of mtDNA levels in control and Tefm knockout hearts at the age of 4 and 8 weeks (Upper 2 blots; n= 6 mice at each time-point for each group). 18S rDNA was used as loading control. DNA isolated from Lrpprc and Mterf4 knockout hearts used as controls. Western blot analyses of VDAC and Histone H3 protein levels in control and Tefm knockout hearts at the age of 4 and 8 weeks (Bottom 2 blots; ; n= 6 mice at each time-point for each group). VDAC represents mitochondria loading and Histone H3 was used as a loading control for nucleus DNA.",
    "ncbi_link": "18S rDNA: 
Lrpprc: 72416
Mterf4: 69821
Tefm: 68550"
  },
  {
    "caption": "Respiratory chain complex activities were measured spectrophotometrically and normalized to citrate synthase activity in heart mitochondria from 8-week-old control and Tefm knockout mice (n= 5 mice for each group). The analyzed enzyme activities are NADH coenzyme Q reductase (complex I), NADH cytochrome c reductase (complex I/III), succinate dehydrogenase (complex II) and cytochrome c oxidase (complex IV).",
    "ncbi_link": "Tefm: 68550"
  },
  {
    "caption": "Barplot of the significantly changed proteins (Benjamini-Hochberg adjusted P <0.05) in Tefm knockout mice compared to control mice (n= 5 mice for each group), organized by individual OXPHOS complexes. Proteins are organized in alphabetic order based on gene name. Bars represent mean log2 [L/L, cre / L/L] ± 95% confidence interval.",
    "ncbi_link": "cre: 2777477
Tefm: 68550"
  },
  {
    "caption": "Western blot analyses of POLRMT protein levels in control and Tefm knockout heart mitochondria at the age of 8 weeks (n= 12 mice for each group). VDAC was used as loading control.",
    "ncbi_link": "Tefm: 68550"
  },
  {
    "caption": "Northern blot analyses and relative quantification of mtRNA transcripts in control and Tefm knockout mouse hearts at the age of 4 and 8 weeks (n= 12 mice at each time-point for each group). 18S rRNA and 5.8S rRNA were used as loading controls, respectively. HSP transcripts: 12S rRNA 4 weeks P= 0.005966044, 8 weeks P= 0.0806819; 16S rRNA 4 weeks P= 0.000223004, 8 weeks P= 0.00243443; Nd1 4 weeks P= 0.0352088, 8 weeks P= 0.000344158; Cox1 4 weeks P= 0.000353895, 8 weeks P= 0.00145773; Cox2 4 weeks P= 0.0145193, 8 weeks P= 0.00578484; Cox3 4 weeks P= 0.00834317, 8 weeks P= 0.000392364; Nd5/Cyb 4 weeks P= 0.0010185, 8 weeks P= 0.00153049; Nd5 4 weeks P= 0.024621, 8 weeks P= 7.38074E-05; Cyb 4 weeks P= 3.46175E-06, 8 weeks P= 0.000991942; LSP transcript: Nd6 4 weeks P= 0.000162704, 8 weeks P= 0.000187855. (E) HSP transcripts: Tf 4 weeks P= 0.0297685, 8 weeks P= 0. 000212544; Tv 4 weeks P= 0.842023, 8 weeks P= 0.269231; Tl1 4 weeks P= 0.00921072, 8 weeks P= 0.000430068; Tm 4 weeks P= 0.0084742, 8 weeks P= 0.000142524; Tk 4 weeks P= 0.00297015, 8 weeks P= 0.00010425; Ts2 4 weeks P= 0.0128829, 8 weeks P= 2.27321E-05; Tl2 4 weeks P= 0.00701324, 8 weeks P= 0.000411549; Tt 4 weeks P= 0.00572118, 8 weeks P= 0.000807943; LSP transcript: Tp 4 weeks P= 0.0427191, 8 weeks P= 0.0483328; Te 4 weeks P= 0.464031, 8 weeks P= 0.13412; Ts1 4 weeks P= 0.0382215, 8 weeks P= 0.000478237; Tc 4 weeks P= 0.00418795, 8 weeks P= 0.000287525; Tn 4 weeks P= 0.00531668, 8 weeks P= 0.000374367; Ta 4 weeks P= 0.00247257, 8 weeks P= 0.000564597; Tq 4 weeks P= 0.00385524, 8 weeks P= 0.000727981.",
    "ncbi_link": "16S rRNA: 
Cox1: 17708
Cox2: 17709
Cox3: 17710
Cyb: 17711
12S rRNA: 17724
Nd1: 17716
Nd5: 17721
Nd6: 17722
18S rRNA: 19791
5.8S rRNA: 790956
Tefm: 68550
Ta: 17726
Tc: 17727
Te: 17729
Tf: 17730
Tk: 17734
Tl1: 17735
Tl2: 17736
Tm: 17737
Tn: 17738
Tp: 17739
Tq: 17740
Tt: 17744
Tv: 17745
Ts1: 110291
Ts2: 110292"
  },
  {
    "caption": "In organello transcription analyses using heart mitochondria isolated from 8-week-old control and Tefm knockout mice (n= 5 mice for each group). The steady-state levels of 12S rRNA and tRNAV were used as endogenous controls, due to their unchanged levels. VDAC was used as loading control for the equal input of mitochondrial extracts. This experiment has performed five times with either two or three replicates.",
    "ncbi_link": "VDAC: 
12S rRNA: 17724
Tefm: 68550
tRNAV: 17745"
  },
  {
    "caption": "Northern blot analyses of 7S RNA level in 4- and 8-week-old control and Tefm knockout mouse hearts (n= 12 mice at each time-point for each group). 18S rRNA was used as loading control. RNA from tissue-specific Mterf4 knockout mouse hearts and tissue-specific Polrmt knockout mouse hearts were loaded as positive and negative control, respectively.",
    "ncbi_link": "Mterf4: 69821
Polrmt: 216151
18S rRNA: 19791
7S RNA: 103952///103948///103950///103951///103953///103958///103973///103974///103975///103949///109569///109568
Tefm: 68550"
  },
  {
    "caption": "Southern blot analyses of mtDNA to obtain 7S DNA in 8-week-old control and Tefm knockout mice. Heart mitochondria from 3 control or knockout mice were pooled for preparation of mtDNA. Equal amounts of mtDNA shown on the top of the gel, were loaded as the endogenous control. This experiment has performed three times.",
    "ncbi_link": "7S DNA: 
Tefm: 68550"
  },
  {
    "caption": "In organello replication assays were performed on heart mitochondria isolated from 8-week-old control and Tefm knockout mice (n= 5 mice for each group). VDAC was used as loading control.",
    "ncbi_link": "VDAC: 
Tefm: 68550"
  },
  {
    "caption": "Northern blot analyses of the 7S RNA levels in 4- and 8-week-old control and Tefm knockout mouse hearts (n= 12 mice for each group). 5S rRNA was used as loading control. RNA from tissue-specific Mterf4 knockout mouse hearts and tissue-specific Polrmt knockout mouse hearts were loaded as positive and negative control, respectively.",
    "ncbi_link": "Mterf4: 69821
Polrmt: 216151
5S rRNA: 19804
7S RNA: 103952///103948///103950///103951///103953///103958///103973///103974///103975///103949///109569///109568
Tefm: 68550"
  },
  {
    "caption": "Strand-specific RT-qPCR detection of the mitochondrial precursor transcripts containing the antisense of mt-tRNAA and antisense of mt-tRNAC in control and Tefm knockout mice (n= 12 mice for each group). The mt-mRNAs are shown in light blue and mt-tRNAs in grey. Arrows show the binding position of RT-qPCR primers. Actin transcript was used as endogenous control.",
    "ncbi_link": "Actin: 
Tefm: 68550
mt-tRNAA: 100093662///100093663///100093664///100093665
mt-tRNAC: 100093680///100093681"
  },
  {
    "caption": "Strand-specific RT-qPCR detection of the mitochondrial precursor transcripts spanning the junction of Nd5 and antisense of Nd6 in control and Tefm knockout mice (n= 25 mice for each group). The mt-mRNAs are shown in light blue. Arrows show the binding position of RT-qPCR primers. Actin transcript was used as endogenous control.",
    "ncbi_link": "Actin: 
Nd5: 17721
Nd6: 17722
Tefm: 68550"
  },
  {
    "caption": "Northern blot analyses of the precursor transcripts containing the antisense of mt-tRNAA in 4- and 8-week-old control and Tefm knockout mouse hearts (n= 6 mice for each group).",
    "ncbi_link": "Tefm: 68550
mt-tRNAA: 100093662///100093663///100093664///100093665"
  },
  {
    "caption": "Volcano plot showing TEFM-BioID. TEFM-BirA*-HA was stably expressed in HEK 293 cells, followed by streptavidin affinity purification and mass spectrometry analysis to detect the associated proteins. Mitochondrial targeted BirA* (MTS-BirA*) was used as a control. The significantly enriched proteins are presented above the horizontal dashed line with 5% false discovery rate (FDR) significance. The blue dots highlight proteins involved in mtDNA transcription and the green dots represent proteins involved in RNA metabolism. All other proteins are in grey.",
    "ncbi_link": "BirA: 
HA: 
MTS: 
TEFM: 79736"
  },
  {
    "caption": "Relative expression of Rab39a in siRNA-treated cells after 48 hours of knockdown. Rab39a expression in I-Ab or Rab39a siRNA-treated cells was normalized to expression in cells treated with control β2m siRNA. Error bars show SD between three independent experiments. * p < 0.05 using two-way Student's t-test.",
    "ncbi_link": "β2m: 12010
I-Ab: 14961
Rab39a: 270160"
  },
  {
    "caption": "XPT of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts of Ova-Fe The cells were then exposed to RF33.70-Luc Reporter CD8 T cells overnight. RLU indicates relative luminescence units produced by reporter T cell stimulation. Error bars show SD of >3 replicate wells. * p < 0.05 vs control I-Ab using two-way ANOVA. Representative plot of 3 independent experiments.",
    "ncbi_link": "Luc: 
I-Ab: 14961"
  },
  {
    "caption": "XPT of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts of Ova-latex The cells were then exposed to RF33.70-Luc Reporter CD8 T cells overnight. RLU indicates relative luminescence units produced by reporter T cell stimulation. Error bars show SD of >3 replicate wells. * p < 0.05 vs control I-Ab using two-way ANOVA. Representative plot of 3 independent experiments.",
    "ncbi_link": "Luc: 
I-Ab: 14961"
  },
  {
    "caption": "XPT of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts of unconjugated soluble Ova The cells were then exposed to RF33.70-Luc Reporter CD8 T cells overnight. RLU indicates relative luminescence units produced by reporter T cell stimulation. Error bars show SD of >3 replicate wells. * p < 0.05 vs control I-Ab using two-way ANOVA. Representative plot of 3 independent experiments.",
    "ncbi_link": "Luc: 
I-Ab: 14961"
  },
  {
    "caption": "DC3.2-Rab39a cells (Rab39a KO with dox-inducible Rab39a) were incubated overnight with or without 1 µg/ml dox to induce Rab39a expression. 1x105 Cells were then fed with Ova-Fe and exposed to reporter T cells as in (B). Error bars show SD of duplicate wells. * p < 0.05 using two-way ANOVA. Representative plot of 3 independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "MHC-II presentation of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts of Ova-Fe. The cells were then exposed to MF2.2D9-Luc Reporter CD4 T cells overnight. Error bars show SD of >3 replicate wells. * p < 0.05 vs negative control β2m using two-way ANOVA. None of the bead concentrations are p < 0.05 for Rab39a siRNA vs β2m. Representative plot of 3 independent experiments",
    "ncbi_link": "Luc: 
β2m: 12010
Rab39a: 270160"
  },
  {
    "caption": "DC3.2-Rab39a cells (Rab39a KO with dox-inducible Rab39a) were incubated overnight with or without 1 µg/ml dox to induce Rab39a expression. 1x105 cells were then fed with Ova-Fe and exposed to reporter T cells as in (A). Error bars show SD of duplicate wells. None of the bead concentrations are p < 0.05 for Rab39a siRNA vs β2m using two-way ANOVA. Representative plot of 3 independent experiments",
    "ncbi_link": "β2m: 12010
Rab39a: 270160"
  },
  {
    "caption": "MHC-I Presentation of SIINFEKL-H2-Kb complexes on siRNA treated DC3.2 NS-Ova (C) or DC3.2 UbS8L (D) cells. 48 hours after siRNA transfection, the indicated amounts of dox was added to the cells to induce Ova expression. After 2 hours at 37oC, RF33.70-Luc CD8 T cells were added along with Brefeldin A (Golgiplug) to a final concentration of 1:1000. The cells were incubated overnight for reporter T cell luciferase expression. Error bars show SD of >3 replicate wells. * p < 0.05 vs negative control I-Ab using two-way ANOVA. None of the dox concentrations are p < 0.05 for Rab39a siRNA vs I-Ab. Representative plot of 3 independent experiments",
    "ncbi_link": "Luc: 
luciferase: 
I-Ab: 14961
Rab39a: 270160"
  },
  {
    "caption": "Rab39a was induced in DC3.2-Rab39a cells (Rab39a KO with dox-inducible Rab39a) via overnight incubation with 1µg / ml dox. KO and rescued cells were then harvested and assayed as in (A) for phagocytosis. Representative plot of two independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "DC3.2-Rab39a cells were induced to express Rab39a overnight. Cells on coverslips were washed, fixed and stained according to the listed protocol and antibodies. Green = Rab39a (HA tag), Magenta = Lamp2. Arrows highlight punctate structures with colocalization. Scale bar = 10 µm. Representative image of two independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "DC3.2 Rab39a KO cells were transduced with dox inducible mcherry-tagged Rab39a. Cells were plated in 35 mm glass bottom dishes and induced with 1 µg/ml dox. The next day, 1 µm latex beads conjugated with Alexa 488-NHS (1 bead/cell) were added. After 2 hours at 37oC, cells were imaged under a Leica TCS SP5 confocal microscope. Green = Alexa 488 labeled beads. Magenta = mcherry-Rab39a. Arrows highlight internalized beads surrounded by Rab39a. Scale bar = 10 µm. Representative image of two independent experiments.",
    "ncbi_link": "mcherry: 
Rab39a: 270160"
  },
  {
    "caption": "5x105 of DC3.2-Rab39a cells were induced to express Rab39a overnight with 1 µg/ml dox in a 6 well plate. Cells were fed at 1 bead/cell of biotinylated-6µm magnetic beads for the indicated lengths of time. Magnetic-bead-phagosomes were isolated using the listed protocol. Phagosomes were washed and stained for Rab39a (HA-tag). Representative data for 3 independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "1.25 x 105 of DC3.2-Rab39a cells were incubated in a 12 well plate overnight ± dox (1µg/ml) to induce Rab39a. Cells were fed at 4 beads/cell of biotinylated-ova-6µm-magnetic-beads for 3 hours with or without 1:1000 BFA (golgiplug, BD). Phagosomes were isolated using the listed protocol. Isolated phagosomes were washed, permeabilized and stained. Shown are histograms of indicated stains as well as % of Rab39a positive phagosomes. Representative plot of two independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "XPT of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts of C8L peptid conjugated to iron oxide beads via a disulfide bond. The cells were then exposed to RF33.70-Luc Reporter CD8 T cells overnight. Error bars show SD of >3 replicate wells. * p < 0.05 for siRNA vs control I-Ab using two-way ANOVA. Representative plot of 3 independent experiments",
    "ncbi_link": "Luc: 
I-Ab: 14961"
  },
  {
    "caption": "XPT of siRNA treated DC3.2R cells after 48 hours of knockdown. Treated cells were fed with the indicated amounts o Ova (B) conjugated to iron oxide beads via a disulfide bond. The cells were then exposed to RF33.70-Luc Reporter CD8 T cells overnight. Error bars show SD of >3 replicate wells. * p < 0.05 for siRNA vs control I-Ab using two-way ANOVA. Representative plot of 3 independent experiments",
    "ncbi_link": "Luc: 
I-Ab: 14961"
  },
  {
    "caption": "DC3.2-Rab39a cells (Rab39a KO with dox-inducible Rab39a) were incubated overnight with or without 1 µg/ml dox to induce Rab39a expression. 1x105 cells were then fed with C8L peptide beads and exposed to reporter T cells as in (A). Error bars show SD of duplicate wells. * p < 0.05 between no dox and + dox using two-way ANOVA. Representative plot of 3 independent experiments",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "Same as in (A) but cells were fed with 8 µg of A9M peptide bead and exposed to 12.64-Luc Reporter T cells. Experiments were combined by normalizing RLU values to the average of the negative control I-Ab. Error bars show SD of 3 independent experiments. * p < 0.05 for Rab39a or β2m siRNA vs negative control I-Ab using ANOVA",
    "ncbi_link": "Luc: 
β2m: 12010
I-Ab: 14961
Rab39a: 270160"
  },
  {
    "caption": "DC3.2-Rab39a-H2-Ld cells (Rab39a KO with dox-inducible Rab39a) were incubated with or without 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were fed at 4 beads/cell of biotinylated-magnetic-beads for 4 hours. Magnetic bead phagosomes were isolated using the listed protocol. Phagosomes were washed, fixed, permeabilized and stained for Open (64-3-7) and Closed (30-5-7s) forms of H2-Ld. Representative histograms shown in (B). The background fluorescence of unstained beads was subtracted from the resulting phagosome gMFI and the fold change of open or closed H2-Ld (dox/no dox) was calculated. Three independent experiments were combined for analysis and error bars show the SD between experiments. Open H2-Ld, but not Closed H2-Ld was statistically significant (p<0.05) between KO and rescued cells using two-tailed ratio-paired Student's t-test.",
    "ncbi_link": "H2-Ld: 14980
Rab39a: 270160"
  },
  {
    "caption": "DC3.2-Rab39a-H2-Ld cells (Rab39a KO with dox-inducible Rab39a) were incubated with or without 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were fed at 4 beads/cell of biotinylated-magnetic-beads for 4 hours. Magnetic bead phagosomes were isolated using the listed protocol. Phagosomes were washed, fixed, permeabilized and stained for Open (64-3-7) and Closed (30-5-7s) forms of H2-Ld. H2-Ld cell surface levels of KO and induced cells as in (A).",
    "ncbi_link": "H2-Ld: 14980
Rab39a: 270160"
  },
  {
    "caption": "DC3.2 Rab39a-H2-Ld cells were incubated with or without 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were fed at 4 beads/cell of biotinylated-Ova-magnetic-beads for 4 hours in the presence or absence of BFA. Isolated phagosomes were stained for H2-Ld. Representative of two independent experiments.",
    "ncbi_link": "H2-Ld: 14980
Rab39a: 270160"
  },
  {
    "caption": "DC3.2-Rab39a-H2-Ld cells (Rab39a KO with dox-inducible Rab39a) were incubated with 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were fed at 4 beads/cell of biotinylated-Ova-magnetic-beads for 4 hours with the indicated inhibitors. Magnetic-bead phagosomes were isolated using the listed protocol. Phagosomes were washed, fixed, permeabilized and stained for Open and Closed (30-5-7s) forms of H2-Ld. Representative histograms of two independent experiments shown.",
    "ncbi_link": "H2-Ld: 14980
Rab39a: 270160"
  },
  {
    "caption": "Cells as in (A) were incubated with or without 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were fed at 4 beads/cell of biotinylated-Ova-magnetic-beads for 4 hours. Phagosomes were isolated and stained for Ova and Open H2-Ld. Representative of 3 independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "Cells as in (A) were incubated with or without 1 µg/ml dox overnight to induce Rab39a expression. 1x106 cells were incubated on ice with 4 beads/cell of biotinylated-Ova-beads for bead attachment. Cells were then transferred into 37oC media containing 5 µM CellROX Deep Red. After 4 hours of incubation, unfixed phagosomes were extracted and analyzed via flow cytometry for CellROX fluorescence. For analysis, the background fluorescence of unstained beads was subtracted from the resulting phagosome gMFI and the fold change (dox/no dox) was calculated. Three independent experiments were combined. P<0.05 using two-tailed ratio-paired Student's t-test. Error bars show SD between experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "DC3.2R cells were treated with the indicated siRNA. 48 hours after transfection, cells were fed with Ova-Fe (2 µg Ova) with or without 100 µM leupeptin. RF33.70-Luc reporter T cells were added. After overnight incubation, T cell luciferase was measured. Representative plot of two independent experiments. Error bars show SD between 3 replicate wells. p values were calculated using 2-way ANOVA.",
    "ncbi_link": "Luc: 
luciferase: "
  },
  {
    "caption": "5x104 DC3.2-Rab39a-H2-Ld cells were fed with Ova-Fe (1µg Ova) with or without 1 µg dox and/or 100 µM leupeptin. RF33.70-Luc reporter T cells were added. After overnight incubation, T cell luciferase was measured. Representative plot of two independent experiments. Error bars show SD between 3 replicate wells. p values were calculated using 2-way ANOVA.",
    "ncbi_link": "Luc: 
luciferase: 
H2-Ld: 14980
Rab39a: 270160"
  },
  {
    "caption": "Rab39a expression in splenocyte subsets was measured using an FDG assay. Shown are relative FDG fluorescence of Rab39a KO cells/WT background. Summary of two independent experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "Splenic DCs were expanded in Rab39a KO and WT mice by injection of B16-Flt3L tumor. 10 days post tumor implantation, DCIR2+ (Cd8α-) or XCR1+ (Cd8α+) dendritic cells were isolated from spleens via magnetic positive selection. 5 x 104 cells were plated in a 96 well plate and incubated with the indicated amounts of Ova-Fe and 1:1 of Reporter CD8 or CD4 T-cells overnight before measuring luciferase activity. Error bars indicate SD of 2 replicate wells. Shown are representative graphs of 3 independent experiments. * p < 0.05 using two-way ANOVA.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "CD11b+ CD11c+ dendritic cells were enriched from WT or Rab39a KO spleens via magnetic negative selection. Cells were fed with 3 µm biotin-ova-magnetic beads for 4 hours. Phagosomes were extracted, permeabilized and stained for the indicated proteins. For ROS measurements, phagocytosis was performed with 5 µM CellROX and the phagosomes were not permeabilized. For analysis, the background fluorescence of unstained beads was subtracted from the resulting phagosome gMFI and the fold change of target (dox/no dox) was calculated. Shown are three independent experiments combined. Error bars show SD between experiments. p values were calculated using two-tailed ratio-paired Student's t-test.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "CD11b+ CD11c+ dendritic cells were enriched from WT or Rab39a KO spleens via magnetic negative selection. Cells were fed with 3 µm magnetic beads conjugated to pHrodo. After 4 hours, cells were harvested for flow cytometry to measure fluorescence of eaten beads due to phagosomal pH. For analysis, the background fluorescence of unstained beads was subtracted from the resulting gMFI and the fold change (dox/no dox) was calculated. Shown are three independent experiments with error bars indicating the SD. p values were calculated using two-tailed ratio-paired Student's t-test.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "CD11b+ CD11c+ dendritic cells were enriched from WT or Rab39a KO spleens via magnetic negative selection. Cells were fed with 3 µm magnetic beads conjugated to Alexa fluor dye. After 4 hours, cells were harvested and resuspended in 1 mg/ml Trypan blue to quench fluorescence of uneaten beads. Cells were run for flow cytometry to measure phagocytosis. The ratio of KO cells with beads / WT cells with beads was then obtained. Graphs show three independent experiments and p values were calculated using two-tailed ratio-paired Student's t-test. Error bars show SD between experiments.",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "Rab39a KO and WT mice were injected intravenously with 1 x 105 A20-Ova cells. The next day, CFSE labeled OTI-splenocytes were injected i.v.. 3 days post OT-I transfer, spleens were harvested and assayed for OT-I proliferation. Three independent experiments (WT vs KO) were performed. To combine the data, the OT-I proliferation in each individual mouse was normalized to the average proliferation of the WT controls in that experiment. Error bars show SD between individual mice and p value was derived from two-tailed student's t-test. n = 14 (WT) or 9 (KO).",
    "ncbi_link": "Rab39a: 270160"
  },
  {
    "caption": "A. Volcano plot for DEGs in the embryonic brain of YFO and AFO at E14.5 (n=3 in each group). Green lines indicate a twofold change and p=0.01. Orange dots indicate REST/NRSF target genes. Data information: Data are presented in the volcano plot or line chart format. *p<0.05, ** p<0.01, ***p<0.001, determined by nominal GSEA p-value.",
    "ncbi_link": "NRSF: 19712
REST: 19712"
  },
  {
    "caption": "A. Volcano plot for DEGs in the embryonic brain of YFO and AFO at E11.5 (n=3 in each group). Green lines indicate a twofold change and p=0.01. Orange dots indicate REST/NRSF target genes. Data information: Data are presented in the volcano plot or line chart format. *p<0.05, ** p<0.01, ***p<0.001, determined by volcano or nominal GSEA P-value. NES, normalized enrichment score.",
    "ncbi_link": "NRSF: 19712
REST: 19712"
  },
  {
    "caption": "(A) SPT activity and Western blot (WB) analysis of S1PR1 in S1pr1f/f and S1pr1ECKO endothelial cells after 4-OHT (1μM, 72h) treatment. (n=8/group from 3 independent EC isolations/group; 4 mice/EC isolation).",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(G,H) SPT activity and WB analysis of HUVEC treated with (G) siCTRL and siNOGO (40nM, 72h) (n≥4/group), or with (H) siCTRL and siORMDL1/2/3 (40nM, 72h) (n=4 biological replicates).",
    "ncbi_link": "NOGO: 116150
ORMDL1: 94101"
  },
  {
    "caption": "(A) WB analysis of ORMDL3 (HA), SPTLC1 and SPTLC2 in HUVEC lysates expressing HA-ORMDL3 and treated with cycloheximide (CHX, 10µM) for the indicated period of time.",
    "ncbi_link": "HA: 
ORMDL3: 94103"
  },
  {
    "caption": "(F) WB analysis of HA-ORMDL3 and HA-ORMDL3-P137A in HUVEC lysates in absence or presence of S1P (300nM, 30'), DMOG (1mM, 1h), EER1 (10µM, 1h), and MG132 (10µM, 1h).",
    "ncbi_link": "HA: 
ORMDL3: 94103"
  },
  {
    "caption": "(G,H) (G) WB analysis of HA-ORMDL3 and HA-ORMDL3-P137A, SPTLC1 and SPTLC2 in HUVEC lysates treated with CHX (10µM) for the indicated period of time, and (H) relative quantification",
    "ncbi_link": "HA: 
ORMDL3: 94103"
  },
  {
    "caption": "(I) WB analysis for Ubiquitin, HA and GFP of HEK293T transfected with GFP-ubiquitin and with the indicated HA-ORMDL3 plasmid, and immunoprecipitated with HA antibody.",
    "ncbi_link": "GFP: 
HA: 
ORMDL3: 94103
ubiquitin: 7316"
  },
  {
    "caption": "SPT activity in S1pr1,3f/f and S1pr1,2ECKO mEC , in absence or presence of S1P (300nM, 30') (B) relative WB analysis for S1PR1, ORMDLs, P-AKT and AKT.",
    "ncbi_link": "S1pr1: 13609"
  },
  {
    "caption": "(A-C) (A) WB analysis of P-VEGFR2 (Y1175), VEGFR2, P-IR (Y1150/1151), IR, P-AKT (S473), AKT, P-eNOS (S1176), and eNOS in Spns2f/f and Spns2ECKO mEC lysates in absence or presence of VEGF (100ng/mL, 2') or Insulin (1U/mL, 2') and (B-C) relative quantification of the indicated phospho/total protein ratios (n≥3 biological replicates).",
    "ncbi_link": "Spns2: 216892"
  },
  {
    "caption": "(D,E) (D) WB analysis of P-VEGFR2 (Y1175), VEGFR2, P-eNOS (S1176), and eNOS in Spns2f/f and Spns2ECKO mEC lysates in absence or presence of VEGF (100ng/mL, 2'), and in absence or presence of Myriocin (300nM) for the indicated time and (E) relative quantification of the indicated phospho/total protein ratios (n≥3 biological replicates).",
    "ncbi_link": "Spns2: 216892"
  },
  {
    "caption": "B. Quantification of PNRC1 expression levels in primary normal (blue circles) and cancer (red circles) samples by Real Time PCR.",
    "ncbi_link": "PNRC1: 10957"
  },
  {
    "caption": "E. Proliferation curves of HeLa cells transfected with HRASG12V (R), PNRC1 (P), their combination (RP) or a LacZ control (L). The results shown are the average ± SD of 2 biological replicates with 3 technical replicates each. A one-way ANOVA with Tukey multiple comparison test was performed for 72h dataset; the statistically significant comparisons are as follows: L vs R (p<0.002), L vs P (p<0.02), R vs P (p<0.0002) and R vs RP (p<0.0004)",
    "ncbi_link": "LacZ: 
HRAS: 3265
PNRC1: 10957"
  },
  {
    "caption": "F. Proliferation curves of MCF7 cells transfected with HRASG12V (R), PNRC1 (P), their combination (RP) or a LacZ control (L). The results shown are the average ± SD of 2 biological replicates with 3 technical replicates each.",
    "ncbi_link": "LacZ: 
HRAS: 3265
PNRC1: 10957"
  },
  {
    "caption": "G. Proliferation curves of KRASG12S-mutated A549 cells transfected with PNRC1 or LacZ control. A representative experiment with the average ± SD of 3 technical replicates is shown. An unpaired t-test was performed for 144h dataset (p<0.0003).",
    "ncbi_link": "LacZ: 
KRAS: 3845
PNRC1: 10957"
  },
  {
    "caption": "H. Proliferation curves of BJ-T cells transduced with a non-targeting or a PNRC1-specific shRNA construct. Results are shown as the average ± SD of 3 biological replicates with 3 technical replicates each. An unpaired t-test was performed for each time point (** p<0.01, *** p<0.005, **** p<0.001).",
    "ncbi_link": "PNRC1: 10957"
  },
  {
    "caption": "A. Click-iT RNA imaging assay performed on HeLa cells expressing RFP-PNRC1 or RFP control. Confocal images of transfected cells pulsed with EU for 16 hours were collected at the indicated time points after EU removal (green: Alexa 488-EU, red: RFP, blue: DAPI, scale bar: 5µm). RFP-PNRC1-transfected cells are indicated with arrowheads.",
    "ncbi_link": "RFP: 
PNRC1: 10957"
  },
  {
    "caption": "D. Agarose/formaldehyde gel separation of neotranscribed rRNAs collected from LacZ and PNRC1-expressing cells pulsed for 15 minutes with 3H-uridine and chased for the reported time points (minutes). Samples were loaded according to the amount of incorporated 3H, quantified by liquid scintillation. FU was included as a control of a blocked rRNA processing.",
    "ncbi_link": "LacZ: 
PNRC1: 10957"
  },
  {
    "caption": "E. Ratios between the intensity of 47S pre-rRNA band and bands belonging to 32S or 28S rRNA species relative to panel (D) and measured at 60 minutes after the chase for both LacZ or PNRC1-expressing cells.",
    "ncbi_link": "28S rRNA: 
32S: 
47S pre-rRNA: 
LacZ: 
PNRC1: 10957"
  },
  {
    "caption": "F. Real Time PCR quantification of 5'-ETS steady-state levels in HeLa cells expressing PNRC1 or GFP control. The average ± SD of 3 biological replicates is shown.",
    "ncbi_link": "GFP: 
PNRC1: 10957"
  },
  {
    "caption": "A. Confocal microscopy images of RFP or RFP-PNRC1-expressing cells stained for DCP1α, DDX6 and LSM1. RFP-PNRC1-transfected cells are indicated with arrowheads. Scale bar: 10µm. B. Quantification of cells classified according to the P-body localization of the three stained proteins. The average ± SD of 3 independent experiments is reported. ",
    "ncbi_link": "RFP: 
PNRC1: 10957"
  },
  {
    "caption": "C. Nucleolar fractionation performed on LacZ or PNRC1-expressing HeLa cells. Total lysates, cytoplasmic (Cyto), nucleoplasmic (Nucl) and nucleolar (No) fractions were collected. UBF1, RNA PolII and MEK2 were used as markers for the nucleolar, non-nucleolar and cytoplasmic fractions, respectively. The electrophoretic mobility of proteins in the nucleoplasmic lanes is slightly diminished due to nuclear lysis buffer composition. D. Densitometric quantification of DCP1α nucleolar pool obtained from the western blot shown in panel (C) and normalized upon the amount of nucleolar UBF1 and the levels of DCP1α in the input fraction. ",
    "ncbi_link": "LacZ: 
PNRC1: 10957"
  },
  {
    "caption": "E. Confocal microscopy images of HeLa cells silenced for the endogenous DCP1α and expressing a shRNA-resistant GFP-DCP1α in combination with RFP or RFP-PNRC1 transgenes (green: GFP, red: RFP, blue: DAPI, scale bar: 5µm).",
    "ncbi_link": "GFP: 
RFP: 
DCP1α: 55802
PNRC1: 10957"
  },
  {
    "caption": "A. Co-immunoprecipitation performed on HeLa cells expressing HA-PNRC1WT, HA-PNRC1W300A or HA-PNRC1ΔNLS with a specific anti-HA antibody and probed with anti-NPM1 and anti DCP1α antibodies.",
    "ncbi_link": "HA: 
PNRC1: 10957"
  },
  {
    "caption": "B-C. Co-immunoprecipitation performed on HeLa cells expressing HA-PNRC1W300A mutant with a specific anti-HA antibody and probed with antibodies specific for PNRC1-interacting proteins. The white arrow indicates the specific DCP2 band.",
    "ncbi_link": "HA: 
PNRC1: 10957"
  },
  {
    "caption": "D. Confocal microscopy images of HeLa cells silenced for the endogenous DCP1α and expressing an shRNA-resistant GFP-DCP1α in combination with RFP, RFP-PNRC1WT or RFP-PNRC1W300A mutant (green: GFP, red: RFP, blue: DAPI, scale bar: 5µm).",
    "ncbi_link": "GFP: 
RFP: 
DCP1α: 55802
PNRC1: 10957"
  },
  {
    "caption": "E. Confocal microscopy images of RFP, RFP-PNRC1 or RFP-PNRC1W300A-expressing cells stained for DCP1α, DDX6 and LSM1. RFP-PNRC1WT or RFP-PNRC1W300A-transfected cells are indicated with arrowheads. Scale bar: 10µm",
    "ncbi_link": "RFP: 
PNRC1: 10957"
  },
  {
    "caption": "F. Quantification of HeLa cells expressing RFP-PNRC1W300A classified according to the P-body localization of the three stained proteins. The average of 3 independent experiments ± SD is reported.",
    "ncbi_link": "RFP: 
PNRC1: 10957"
  },
  {
    "caption": "G. Co-immunoprecipitation performed on HeLa cells expressing LacZ control, HA-PNRC1WT, HA-PNRC1W300A or HA-PNRC1ΔNLS constructs with a specific anti-DCP1α antibody and probed with anti-PNRC1 and anti-NPM1 antibodies.",
    "ncbi_link": "HA: 
LacZ: 
PNRC1: 10957"
  },
  {
    "caption": "A. Confocal images of a Click-iT RNA imaging assay performed on HeLa cells expressing RFP-PNRC1W300A pulsed with EU for 16 hours and collected at the indicated time points after EU removal (green: Alexa 488-EU, red: RFP, blue: DAPI, scale bar: 5µm). RFP-PNRC1WT or RFP-PNRC1W300A-transfected cells are indicated with arrowheads.",
    "ncbi_link": "RFP: 
PNRC1: 10957"
  },
  {
    "caption": "B. Real Time PCR quantification of 5'-ETS steady-state levels in HeLa cells expressing PNRC1W300A or GFP control. The average of 3 independent experiments ± SD is reported.",
    "ncbi_link": "GFP: 
PNRC1: 10957"
  },
  {
    "caption": "C. Quantification of 5'-ETS RNA levels in HeLa cells infected with an anti-DCP2 or a non-targeting shRNA and expressing GFP, PNRC1WT or PNRC1W300A transgenes. The average of 2 independent experiments ± SD is reported.",
    "ncbi_link": "GFP: 
DCP2: 167227
PNRC1: 10957"
  },
  {
    "caption": "Levels of U3 (D) snoRNAs immunoprecipitated by the anti-m3G cap antibody measured by Real Time PCR. Values represents the average of two biological replicates with three technical replicates and are",
    "ncbi_link": "U3: "
  },
  {
    "caption": "Levels of U8 (E) snoRNAs immunoprecipitated by the anti-m3G cap antibody measured by Real Time PCR.",
    "ncbi_link": "U8: "
  },
  {
    "caption": "F. Levels of U3 snoRNA immunoprecipitated by the anti-m3G cap antibody in HeLa cells infected with an anti-DCP2 or a non-targeting shRNA and expressing GFP, PNRC1WT or PNRC1W300A transgenes. The average ± SD of 2 independent experiments with three technical replicates is reported.",
    "ncbi_link": "GFP: 
U3 snoRNA: 
DCP2: 167227
PNRC1: 10957"
  },
  {
    "caption": "G. Western blot analysis of input and Flag-IP fractions of RIP experiment. H. RNA levels of U3, U8 and U1 co-immunoprecipitating with GFP, PNRC1WT or PNRC1W300A. Results are shown as the average ± SD of two biological replicates.",
    "ncbi_link": "U1: 
U3: 
U8: "
  },
  {
    "caption": "Figure 1: Endothelial Ang-2 upregulation correlates with WHO grading in human gliomas. ELISA displaying human Ang-2 (A) and Ang-1 (B) level in serum of healthy patients (Ang-2 n=4; Ang-1 n=21) or patients with low grade glioma (WHOII) (n=5), anaplastic astrocytoma (WHOIII) (n=7) or glioblastoma (WHOIV) (n=39) are shown. The TCGA database was accessed to obtain gene expression level for Ang-1, Ang-2, Tie2 and Tie1 in GBM in comparison to normal brain (C).",
    "ncbi_link": "Ang-1: 284
Ang-2: 11601
Tie2: 7010
Tie1: 7075"
  },
  {
    "caption": "Figure 2: Endothelial Ang-2 expression reduced pericyte coverage and increased macrophage infiltration in experimental glioblastoma. GL261 cells were intracerebrally transplanted in wild type or Ang-2 gain-of-function mice (Ang-2 DT). Brain tumor sections were stained with antibodies against CD31 and desmin (A), and microvessel densities (MVD) and pericyte coverage were determined (WT n=14; Ang-2 DT n=6) (B).",
    "ncbi_link": "Ang-2: 11601"
  },
  {
    "caption": "FACS analysis of infiltrating macrophages in Ang-2 DT normal brain (w/o tumor) compared to WT is shown (C, dot plot; D, quantification) (WT n=5; Ang-2 DT n=3).",
    "ncbi_link": "Ang-2: 11601"
  },
  {
    "caption": "). Immunohistochemistry staining for monocytes/macrophages (F4/80) and neutrophils (Ly6G; arrowheads) in brain tumors derived from WT or Ang-2 overexpressing mice (E), Quantitative analysis of C (F) (WT n=14; Ang-2 DT n=10)",
    "ncbi_link": "Ang-2: 11601"
  },
  {
    "caption": "Kaplan-Meier survival curve of GL261 tumor-bearing WT and Ang-2 DT mice (WT n=17; Ang-2 DT n=14) (E). Statistical analyses were performed using an unpaired Student´s t-test (B, F), one-way Anova (Tukey post test) (D), Log-rank and Wilcoxon (G) * p < 0.05, ** p < 0.01; data are mean ± SEM",
    "ncbi_link": "Ang-2: 11601"
  },
  {
    "caption": "Figure 4: Dual anti-Ang-2 and anti-VEGF therapy acts synergistic on vascular normalization and macrophage infiltration in experimental GBM. Immunofluorescence staining of CD31 and desmin in GL261 glioblastoma after single and dual treatment with anti-Ang-2 (AMG386) and anti-VEGF (aflibercept) (A). Corresponding quantitative analysis of microvessel densities and pericytes numbers (B; control n=24; AMG386 n=10; aflibercept n=12; AMG386 + aflibercept n=13).",
    "ncbi_link": "Ang-2: 11601
VEGF: 22339"
  },
  {
    "caption": "Double-immunofluorescence stainings with anti-F4/80 and anti-CD206 in brain tumor sections of mice treated with anti-Ang-2 (AMG386), anti-VEGF (aflibercept) or the combination of both are shown in (J). Corresponding quantitative analyses of tumor infiltrating F4/80+ cells and CD206+ cells, and the ratio of CD206+ vs. F4/80+ upon anti-angiogenic therapy are displayed in (K; control n=21; AMG386 n=13; aflibercept n=9; AMG386 + aflibercept n=4).",
    "ncbi_link": "Ang-2: 11601
VEGF: 22339"
  },
  {
    "caption": "Figure 5: Anti-VEGF therapy led to decreased infiltration of CD68+ macrophages in human GBM. Anti-CD68 (A), anti-CSFR1 (B) and anti-CD206 (C) immunohistochemistry of patient samples derived from treatment-naive GBM (n=24), post-radiochemotherapy (S/RTx/CTx) (n=7) and post-radiochemotherapy + bevacizumab (S/RTx/CTx/Bev) (n=29) therapy is shown.",
    "ncbi_link": "VEGF: 7422"
  },
  {
    "caption": "(A-H) Expression of Tecrl in mouse development. Expression is not observed in (A) the cardiac crescent at E7.5 but is prominent in (B) the inflow tract (ift) region at E8.5, particularly in (C) the left sinus venosus (lsv). (D) At E9.5, Tecrl expression is observed in all four chambers of the heart but is strongest in the inflow tract. (E-G) From E10 onwards, Tecrl is expressed in the somites. (H) At E14.5, Tecrl expression is present in the entire myocardium; [atrium (a), ventricle (v), neural tube (nt), lung (lu), right atrium (ra), left atrium (la), right ventricle (rv) and left ventricle (lv)].",
    "ncbi_link": "Tecrl: 243078"
  },
  {
    "caption": "(I) mRNA expression analyses of TECR and TECRL by RT-qPCR in human tissues demonstrates preferential expression of Tecrl in the heart; [Bone marrow (Bone M.), heart, skeletal muscle (Sk.Muscle), uterus, liver, spleen, thymus, thyroid, prostate, brain, lung, small intestine (Small I.) and colon]",
    "ncbi_link": "TECR: 9524
TECRL: 253017
Tecrl: 253017"
  },
  {
    "caption": "(A) Skin fibroblasts(left) from IV:13, homozygous for the TECRLc.331+1G>A mutation were reprogrammed to hiPSCs(center), which expressed the pluripotency markers NANOG and SSEA4(right). Scale bars: 100 μm.",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(B) TECRLHom-hiPSCs have a normal karyotype(left) and PluriTest demonstrates a high pluripotency score and low novelty score for all three hiPSC lines (right).",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(C) TECRLHom-hiPSCs generate derivatives of mesoderm(left), endoderm(center) and ectoderm(right). Scale bars: 25 μm",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(F) ACTN2 immunostaining of CTRL-, TECRLHet- and TECRLHom-hiPSC-CMs. Scale bar: 25 μm.",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(G) Analysis of RT-PCR products by gel electrophoresis. Amplification products of TECRL exons 2-4 from CTRL-, TECRLHet- and TECRLHom-hiPSC-CMs(left) and coding sequence of TECRL from CTRL- and TECRLHom-hiPSC-CMs(right).",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(C) Rate constants of SERCA-, NCX- and slow mechanisms-based [Ca2+]i decay in hiPSC-CMs. (D) Relative contribution of SERCA, NCX and slow mechanisms to [Ca2+]i extrusion in hiPSC-CMs.",
    "ncbi_link": "SERCA: 489///488///487"
  },
  {
    "caption": "(A) AP illustrating the analysed parameters (B) Representative APs from control (CTRL), heterozygous (HET) and homozygous (HOM) CMs. (C) RMP, dV/dtmax , APAmax, APAplat, APD20, APD50 and APD90 of CTRL-, TECRLHet- and TECRLHom-hiPSC-CMs.",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(A) Representative AP trace of a TECRLHom-hiPSC-CM in the presence of NA alone or NA and flecainide. (B) Effect of flecainide on AP parameters of hiPSC-CMs. (C-D) Addition of 5 μM of flecainide decreased the susceptibility to triggered activity in hiPSC-CMs. Note that the effect of flecainide on triggered activity of TECRLHet- and TECRLHom-hiPSC-CMs is more pronounced than its effect on their spontaneous activity.",
    "ncbi_link": "TECRL: 253017"
  },
  {
    "caption": "(a) Representative photographs of Bax/Bak−/− MEFs treated with etoposide. Bax/Bak−/− MEFs were treated with 20 μM etoposide in the presence of PI (2 μM) for the indicated times, and were analysed under a phase-contrast and fluorescence (PI) microscope.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(b, c) Reduced viability of Bax/Bak−/− MEFs after exposure to etoposide. WT (circles) and Bax/Bak−/− (squares) MEFs were treated with 20 μM etoposide in the presence (closed symbols) or absence (open symbols) of 100 μM zVAD-fmk. Then cell viability was measured by the PI staining (b) and CTB assay (c), and expressed as a percentage of the initial value without etoposide. Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(d) Reduced viability of etoposide-treated Bax/Bak−/− MEFs as assessed by proliferation assay. Bax/Bak−/− MEFs were either not treated (0 h) or were treated with 20 μM etoposide for 12 and 24 h, then all cells were recovered and 5,000 cells were reseeded. Viable cell numbers were measured on the indicated days by the CTB assay. Results were normalized by adjusting the day 0 value. n = 4.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "e) Reduced viability of Bax/Bak−/− MEFs after exposure to etoposide and staurosporine, as assessed by clonogenicity assay. MEFs were treated with etoposide (20 μM) or staurosporine (1 μM) at the indicated times, collected, and 2,000 cells were seeded in the normal medium. After 1 week, colonies were counted. n = 4",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "f-i) Induction of autophagy in Bax/Bak−/− MEFs by etoposide. (f) Electron micrograph (×14,800) of Bax/Bak−/− MEF treated with etoposide (20 μM) for 18 h. Representative features of Bax/Bak−/− MEFs that have received no treatment (NT; that is, are healthy) are also shown (NT: ×14,000).",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(h, i) Punctate GFP-LC3 fluorescence in Bax/Bak−/− MEFs treated with etoposide. GFP-LC3-transfected cells were incubated with and without etoposide (20 μM) for 24 h (h) or the indicated times (i), and then examined by fluorescent microscopy. (h) Representative photographs of healthy (NT) and etoposide-treated Bax/Bak−/− MEFs are shown. (i) The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-positive cells. Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(a, b) Bax/Bak−/− MEFs were treated with 20 μM etoposide in the absence or presence of 10 mM 3-MA for 24 h, and then were examined by phase-contrast microscopy (a) and electron microscopy (×8,400) (b). Autolysosomes/autophagosomes were hardly observed. (",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "c, d) Reduction of punctate GFP-LC3 fluorescence in Bax/Bak−/− MEFs by 3-MA. Bax/Bak−/− MEFs that were transfected with GFP-LC3 were incubated without (NT) or with 20 μM etoposide in the presence or absence of 10 mM 3-MA for 24 h, and then were examined by confocal fluorescent microscopy. (c) Representative photograph of etoposide-treated Bax/Bak−/− MEFs in the presence of 3-MA. (d) The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-LC3-positive cells. Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(c, d) Reduction of punctate GFP-LC3 fluorescence in Bax/Bak−/− MEFs by 3-MA. Bax/Bak−/− MEFs that were transfected with GFP-LC3 were incubated without (NT) or with 20 μM etoposide in the presence or absence of 10 mM 3-MA for 24 h, and then were examined by confocal fluorescent microscopy. (c) Representative photograph of etoposide-treated Bax/Bak−/− MEFs in the presence of 3-MA. (d) The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-LC3-positive cells. Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(e-g) Inhibition of etoposide- and staurosporine-induced cell death by 3-MA. Bax/Bak−/− MEFs were treated with 20 μM etoposide (e-g) or 1 μM staurosporine (g) in the absence (open symbols) or presence (closed symbols) of 10 mM 3-MA for the indicated time. Cell viability was measured by PI staining (e), CTB assay (f) and clonogenicity assay (g) (as in Fig. 1e). Upper panels in g: viable cells were visualized by staining with calcein-AM. n = 4.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(a, b) Bax/Bak−/− MEFs were treated with the indicated siRNAs (10 μg) for 24 h and then incubated with 20 μM etoposide for the indicated times. Expression of APG5-APG12 complex (a), Beclin 1 (b) and VDAC (loading control) was analysed by Western blot analysis.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "(c) Inhibition of etoposide-induced autophagy by silencing of Beclin 1. Bax/Bak−/− MEFs with silencing of Beclin 1 were treated with 20 μM etoposide at 18 h and were analysed by electron microscopy (×8,500).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Beclin 1: 56208"
  },
  {
    "caption": "d) Reduction of punctate GFP-LC3 fluorescence in Bax/Bak−/− MEFs by silencing of Beclin 1 and APG5. Bax/Bak−/− MEFs that were transfected with GFP-LC3 together with the indicated siRNAs, were incubated without (NT) or with 20 μM etoposide for 24 h, and then examined by confocal fluorescent microscopy. The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-LC3-positive cells. Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "APG5: 11793
Bak: 12018
Bax: 12028
Beclin 1: 56208"
  },
  {
    "caption": "(e, f) Inhibition of etoposide- and staurosporine-induced cell death by silencing of Beclin 1 and APG5. Bax/Bak−/− MEFs that were treated with the indicated siRNAs were incubated with 20 μM etoposide (e, f) or 1 μM staurosporine (f) for the indicated time. Cell viability was measured by CTB assay (e) and clonogenicity assay (f). n = 4.",
    "ncbi_link": "APG5: 11793
Bak: 12018
Bax: 12028
Beclin 1: 56208"
  },
  {
    "caption": "(a, b) APG5-dependent punctate GFP-LC3 fluorescence in Bcl-2-transfected MEFs after etoposide treatment. APG5+/+ and APG5−/− MEFs that were transfected with both GFP-LC3 and the indicated plasmids (Bcl-2 or vector) were incubated without or with 20 μM etoposide for 24 h, then examined by confocal fluorescent microscopy (a). The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-LC3-positive cells (b).",
    "ncbi_link": "APG5: 11793
Bcl-2: 12043"
  },
  {
    "caption": "(c) Accumulation of Beclin 1 and APG5-APG12 complex in Bcl-2-transfected MEFs after etoposide treatment. WT MEFs were transfected with the indicated plasmids, and were incubated without (NT) or with 20 μM etoposide for 24 h.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(d, e) Occurrence of etoposide-induced 3-MA-inhibitable non-apoptotic death in Bcl-xL-overexpressing APG5+/+ MEFs, but not APG5−/− MEFs. APG5+/+ (open columns) and APG5−/− (closed columns) MEFs were transfected with the indicated plasmids (2 μg). After 24 h, transfected cells were incubated with 20 μM of etoposide in the presence or absence of 100 μM of zVAD or 10 mM of 3-MA for 24 h, and cell viability was measured by the CTB assay (d) and apoptotic nuclear morphology (e). Data are shown as mean ± s.d. (n = 4).",
    "ncbi_link": "APG5: 11793
Bcl-xL: 12048"
  },
  {
    "caption": "(f) Overexpression of Bcl-xL does not sensitize Beclin 1-silenced MEFs to etoposide-induced 3-MA-inhibitable non-apoptotic death. WT MEFs with silencing of control GFP (open columns) or Beclin 1 (closed columns) were transfected with the indicated plasmids (1 μg). After 24 h, transfected cells were incubated with 20 μM of etoposide in the presence or absence of 10 mM of 3-MA for 24 h, and cell viability was measured by the CTB assay. n = 3.",
    "ncbi_link": "Bcl-xL: 12048
Beclin 1: 56208"
  },
  {
    "caption": "(a) Enhancement of etoposide-induced non-apoptotic death by overexpression of human Bcl-2 and Bcl-xL in Bax/Bak−/− MEFs in a Beclin 1-dependent manner. Bax/Bak−/− MEFs with silencing of control Bax or Beclin 1 were transfected with the indicated plasmids (1 μg). After 24 h, the transfected cells were incubated with 20 μM etoposide for 24 h, and cell viability was assessed by the CTB assay. Data are shown as mean ± s.d. (n = 3).",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-2: 12043
Bcl-xL: 12048
Beclin 1: 56208"
  },
  {
    "caption": "(b) Bax/Bak−/− MEFs were transiently transfected with 10 μg of siRNA for Bcl-2, Bcl-x, or Bax (negative control) for 24 h. Expression levels of Bcl-2, Bcl-xL and Lamin B (loading control) were analysed by Western blot analysis.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-2: 12043
Bcl-x: 12048"
  },
  {
    "caption": "(c-e) Inhibition of etoposide-induced autophagy in Bax/Bak−/− cells treated with siRNA for Bcl-x. (c) Bax/Bak−/− MEFs that were transfected with the indicated siRNAs were treated with 20 μM etoposide for 24 h, then examined by phase-contrast microscopy.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-x: 12048"
  },
  {
    "caption": "(d) Bax/Bak−/− MEFs that were transfected with siRNA for Bcl-x and then treated with etoposide for 18 h were analysed by electron microscopy (×8,500)",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-x: 12048"
  },
  {
    "caption": "(e) Reduction of punctate GFP-LC3 fluorescence in etoposide-treated Bax/Bak−/− MEFs by silencing of Bcl-x. Bax/Bak−/− MEFs that were transfected with both GFP-LC3 and the indicated siRNAs were incubated without (NT) or with etoposide for 24 h, and then were examined by confocal fluorescent microscopy. The percentage of cells with punctate GFP-LC3 fluorescence was calculated relative to all GFP-LC3-positive cells. n = 4.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-x: 12048"
  },
  {
    "caption": "f) Inhibition of etoposide-induced cell death by silencing of Bcl-x. Bax/Bak−/− MEFs were transfected with siRNA (circles, siRNA for Bax; squares, siRNA for Bcl-x) were treated with 20 μM etoposide in the absence (open symbols) or presence (closed symbols) of 10 mM 3-MA, and cell viability was assessed by the CTB assay at the indicated times. n = 4.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-x: 12048"
  },
  {
    "caption": "(g) Clonogenicity assay of Bax/Bak−/− MEFs after exposure to etoposide and staurosporine. Bax/Bak−/− MEFs that were transfected with the indicated siRNAs were treated with 20 μM etoposide or 1 μM staurosporine at 24 h. After collection, 2,000 cells were seeded in the normal medium. After one week, colonies were counted.",
    "ncbi_link": "Bak: 12018
Bax: 12028"
  },
  {
    "caption": "h, i) Inhibition of APG5-APG12 induction by silencing of Bcl-x or Beclin 1. Bax/Bak−/− MEFs were treated with the indicated siRNAs (10 μg) for 24 h and then incubated with 20 μM etoposide for the indicated times. Expression of APG5-APG12 complex, Beclin 1 and GAPDH/VDAC (loading control) was analysed by Western blot analysis.",
    "ncbi_link": "Bak: 12018
Bax: 12028
Bcl-x: 12048"
  },
  {
    "caption": "A HeLa cells were transfected with constructs for a non-targeting shRNA (NT), USP17 shRNA1, or USP17 shRNA2. Cells were stained using an anti-LAMP1 antibody (green) and the nuclei counterstained with DAPI (blue). Lower panels are enlarged images of indicated area in top panels and the cell membrane is marked by dotted line. B HeLa and MDA-MB-231 cells were transfected as in A and the distribution of LAMP1 positive vesicles was plotted as vesicle relative position (see C). C",
    "ncbi_link": "USP17: 645836///377630///401447"
  },
  {
    "caption": "A HeLa cells were transfected with constructs for a non-targeting (NT) shRNA, USP17 shRNA1 or USP17 shRNA2. 48 hours post transfection the cells were either serum starved (upper panels), or treated with serum free medium containing 100ug/ml EGF (lower panels) for 16 hours prior to staining for LAMP1 (green) and DAPI (blue). Right hand panels are enlarged images of the indicated area in left panels and the cell membrane is marked by dotted line. Scale bar represents 25μm. B The distribution of at least 300 LAMP1 positive vesicles from a number of cells (n) from a series of confocal images across three separate experiments was plotted as vesicle relative position (mean value is red bar). Error bars represent standard error, ns indicates not significant, and **** indicates a p-values less than 0.0001. One way ANOVA used to determine if statistically significant differences between groups.",
    "ncbi_link": "USP17: 645836///377630///401447"
  },
  {
    "caption": "A HeLa cells were transfected with negative control siRNA and RNF26 siRNA as well as constructs coding a non-targeting (NT) shRNA, USP17 shRNA1 or USP17 shRNA2, as indicated. 48 hours post transfection cells were stained for LAMP-1 (green) and DAPI (blue). Lower panels are enlarged images of indicated area in top panels and the cell membrane is marked by dotted line. Scale bar represents 25μm.",
    "ncbi_link": "RNF26: 79102
USP17: 645836///377630///401447"
  },
  {
    "caption": "C HeLa cells were transfected with expression constructs for HA-tagged p62 and FLAG-tagged ubiquitin as well as empty vector, USP17 or USP17CS. After 48hrs cell lysates were prepared and HA tagged proteins were pulled down using anti-HA agarose. Pull downs, and lysates, were immunoblotted with anti-HA, anti-FLAG, and anti-USP17 antibodies, as indicated, to confirm the presence of ubiquitinated p62.",
    "ncbi_link": "FLAG: 
HA: 
USP17CS: 
p62: 8878
USP17: 645836///377630///401447"
  },
  {
    "caption": "A HeLa cells were transfected with constructs for EEA1-GFP and RAB5-GFP in addition to non-targeting scrambled (NT) shRNA, USP17 shRNA1 or USP17 shRNA2. 72 hours post transfection the cells were stained with DAPI. The scale bar represents 25μm. B The distribution of at least 400 EEA1 or RAB5 positive vesicles from a number of cells (n) from a series of confocal images across three separate experiments was plotted as vesicle relative position (mean value is red bar). Error bars represent standard error and **** indicates a p-values less than 0.0001. One way ANOVA used to determine if statistically significant differences between groups. E",
    "ncbi_link": "USP17: 645836///377630///401447"
  },
  {
    "caption": "A. Volcano blot representation of the differently expressed genes in FCRLS- and CD11b- positive Grn-/- microglia in comparison to wt microglia isolated from 5.5-month-old mice (male, n = 5). 116 genes out of 529 genes analyzed, are significantly changed, and from these 58 genes are up- and 58 genes are down regulated. Eight genes with the highest fold change are highlighted.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "B. Heatmap of significantly affected genes (p < 0.05) in FCRLS- and CD11b-positive Grn-/- microglia in comparison to Grn+/+ microglia isolated from 5.5-month-old mice (n = 5 per genotype). For the significantly affected genes of the Grn-/- microglia, mRNA expression data of the Trem2-/- microglia in comparison to the corresponding wt microglia were taken from previously published data (Mazaheri et al, 2017). The RNA counts for each gene and sample were normalized to the mean value of wt followed by a log2 transformation (n ≥ 5 per genotype). * labelled genes were not analyzed or below detection limit in Trem2-/- microglia mRNA expression data set (Mazaheri et al, 2017).",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "D. Gene expression levels of FCRLS- and CD11b-positive Grn-/- microglia normalized to wt in comparison to the published normalized data set of Trem2-/- microglia (Mazaheri et al, 2017).",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "A. Immunoblot analysis of ApoE, CLEC7A, TREM2 and CD68 in lysates of acutely isolated microglia from Grn-/- and Grn+/+ mice (9 months of age, n=3 per genotype, female). IBA1 was used as loading control.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "B. Quantification of protein expression normalized to levels of Grn+/+ microglia (n=3). Data represent the mean ± SD.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "C. ELISA mediated quantification of sTREM2 in brain homogenates of Grn-/- and Grn+/+ mice Data are shown as mean ± SEM (n=3-6). D. ELISA mediated quantification of sTREM2 in serum of Grn-/- and Grn+/+ mice. Data are shown as mean ± SEM (n=4-13). ",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "E. Microglial expression of P2RY12 in cortical sections of wt, Grn-/-and Trem2-/- mice. (9 months of age, female) F. Quantification of P2RY12 positive microglia. Data are shown as mean ± SD (n=3 per genotype, female, except one male for Trem2-/-). ",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "G. Immunoblot analysis of secreted PGRN and ApoE (ApoEmed) in conditioned media and PGRN, ApoE, CLEC7A, P2RY12 and TREM2 in lysates of BV2 wild type (Grnwt) and PGRN deficient (Grnmut) cells. Soluble amyloid precursor protein (APPs) and calnexin were used as a loading control.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "H. Quantification of Immunoblots normalized to BV2 Grnwt levels (n=3-5). Data represent the mean ± SD.",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "I. ELISA mediated quantification of sTREM2 in conditioned media of BV2 Grnwt and Grnmut cells. Data represent the mean ± SD",
    "ncbi_link": "Grn: 14824"
  },
  {
    "caption": "J. Quantification of relative mRNA levels of Apoe, Clec7a, P2ry12 and Trem2 in BV2 Grnwt and Grnmut cells. Data represent the mean ± SD.",
    "ncbi_link": "Apoe: 11816
Clec7a: 56644
Grn: 14824
P2ry12: 70839
Trem2: 83433"
  },
  {
    "caption": "B. Enhanced migration of CD68 positive, PGRN deficient cells in an ex vivo model. Immunofluorescence analysis of cultured Grn+/+ and Grn-/- organotypic brain at 7 DIV immunostained using microglial marker CD68. Nuclei were counterstained using DAPI. Images of boxed regions in left panels are shown at higher magnifications in right panels. Scale bars: 500 µm (left panels), 250 µm (right panels). Quantitative analysis reveals that Grn-/- microglia migrate larger distances than Grn+/+. Data are shown as mean ± SD (n=3 independent experiments) Quantification displays an increased number of migrating Grn-/- cells compared to Grn+/+ cells. Data are shown as mean ± SD (n=3 independent experiments)",
    "ncbi_link": "Grn: 14824
PGRN: 14824"
  },
  {
    "caption": "E. Enhanced microglial clustering around amyloid plaques in the absence of PGRN. Left: IBA1-stained microglia clustering around X-34-positive amyloid plaque cores in 4-month-old APPPS1/Grn+/+ mice. Right: Age-matched APPPS1/Grn-/- mice display microglial hyper-clustering around amyloid plaques compared to APPPS1/Grn+/+. Dotted white boxes indicate the area that is shown at higher magnification. Scale bars indicate 10µm and 3µm in inset. Immunohistochemical quantification of IBA1 positive microglial cell number per plaqu",
    "ncbi_link": "Grn: 14824
PGRN: 14824"
  },
  {
    "caption": "A. TSPO-µPET in rodents: Axial slices (A1, A2, A3) of averaged %-TSPO-PET differences between Grn-/-or Trem2-/- mice and wt indicate increased microglial activity in the cerebrum of Grn-/- mice (hot color scale) and decreased microglial activity in the cerebrum of Trem2-/- mice (cold color scale). Scatter plot depicts single TSPO-µPET values deriving from a neocortical volume-of-interest. µPET results are illustrated upon an MRI template; 6-10 female mice per group (Grn-/- n=6 at 8 months, Trem2-/- n=8 at 11 months; wt n=10 at 8-11 months). Statistics derive from one-way ANOVA with Tukey post-hoc test.",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "B. PGRN serum levels of the patients subjected to TSPO-PET confirmed the GRN mutation and non-GRN mutation carrier. PGRN was measured by ELISA and normalized to serum levels of a healthy control.",
    "ncbi_link": "GRN: 2896"
  },
  {
    "caption": "C. TSPO-PET in human FTLD patients: Visual interpretation of axial TSPO-PET SUVR images in upper cranial layers reveals increased microglial activity in frontal and parietal cortices (white arrows) of a FTLD patient with a GRN loss of function mutation in comparison to a FTLD patient without a GRN mutation. PET results are illustrated upon an MRI template; 60-80 min p.i. emission recording; global mean scaling. Both patients were low-affinity binder.",
    "ncbi_link": "GRN: 14824"
  },
  {
    "caption": "FDG-µPET in rodents: Axial slices (as indicated in Fig. 4A) of averaged %-FDG-µPET differences between Grn-/-or Trem2-/- mice and wt indicate decreased glucose metabolism in the cerebrum of Grn-/- and Trem2-/- (both cold color scale) when compared to wt. Scatter plot depicts single FDG-PET values deriving from a neocortical volume-of-interest. µPET results are illustrated upon an MRI template; 6-10 female mice per group (Grn-/- n=6 at 8 months, Trem2-/- n=6 at 11 months; wt n=10 at 8-11 months).",
    "ncbi_link": "Grn: 14824
Trem2: 83433"
  },
  {
    "caption": "D. Immunoprecipitation and western blotting were performed in OSCs upon RNAi treatment (kd). Even without the association of Yb, Armi, SoYb, and Vret associated. Yb and Armi remained bound to each other upon SoYb or Vret depletion. The level of SoYb (input) decreased upon Vret depletion. Likewise, the level of Vret (input) decreased upon SoYb depletion.",
    "ncbi_link": "SoYb: 34331
Vret: 42695"
  },
  {
    "caption": "E. Upon Armi depletion, SoYb and Vret were still bound to each other but this heterodimer no longer associated with Yb.",
    "ncbi_link": "Armi: 38427"
  },
  {
    "caption": "F. Immunofluorescence analyses in OSCs. Yb bodies disappeared upon Yb depletion, which led Armi, SoYb and Vret to be localized in the cytosol. Yb bodies were detected in OSCs upon Armi depletion, but SoYb and Vret localized in the cytosol. Armi was detected at Yb bodies upon SoYb or Vret depletion. Yb bodies are indicated by white arrows. Nuclei are shown in blue. Scale bar: 2 μm.",
    "ncbi_link": "Armi: 38427
Yb: 31262
SoYb: 34331
Vret: 42695"
  },
  {
    "caption": "B. In Yb-lacking OSCs (Yb kd), WT Yb and ∆eTud bound to Armi but ∆eTud did not. Note that WT Yb and both mutants were engineered to be RNAi-resistant by mutations. β-gal was used as a negative control.",
    "ncbi_link": "Yb: 31262
β-gal: 33839"
  },
  {
    "caption": "C. In normal OSCs, WT Yb and ∆eTud bound with Yb but ∆Hel-C did not.",
    "ncbi_link": "Yb: 31262"
  },
  {
    "caption": "D. Flag-Hel-C copurified with Myc-Hel-C but not with BSD (negative control).",
    "ncbi_link": "Flag: 
Myc: 
BSD: 5657695"
  },
  {
    "caption": "E. Subcellular localization of WT Yb and deletion mutants ∆Hel-C and ∆eTud. Myc-Yb is shown in green. Endogenous Armi is shown in red. DAPI shows nuclei (blue). Scale bar: 5 μm. Western blotting (right) showing WT Yb and deletion mutants ∆Hel-C and ∆eTud expressed in Yb-lacking OSCs.",
    "ncbi_link": "Yb: 31262"
  },
  {
    "caption": "F. CLIP shows that WT Yb and ∆Hel-C bind RNA in vivo but ∆eTud does not.",
    "ncbi_link": "Yb: 31262"
  },
  {
    "caption": "A. Rescue experiments showing that ∆Hel-C but not ∆eTud restored piRNA biogenesis attenuated by endogenous Yb depletion. Flag-Piwi was expressed upon endogenous Yb depletion.",
    "ncbi_link": "Flag: 
Yb: 31262"
  },
  {
    "caption": "C. Mapping of flam-piRNAs produced in the presence and absence of the Hel-C domain in OSCs. D. Mapping of tj-piRNAs produced in the presence and absence of the Hel-C domain in OSCs. ",
    "ncbi_link": "flam: 26067356
tj: 35227"
  },
  {
    "caption": "F. The relative enrichments of RNAs coimmunopurified with WT Yb and ∆Hel-C. Bars and error bars represent means ± SEM values of three independent experiments. In addition to tj, three genic piRNA sources that were characterized in previous studies (dm/Myc [59], c-Fos/kay [60], and CG9257 [34]) are also shown. rp49 was used as a negative control. p value was calculated by t-test. ***: p < 0.001.",
    "ncbi_link": "CG9257: 35375
Yb: 31262
kay: 3772082
c-Fos: 3772082
Myc: 31310
dm: 31310
rp49: 43573
tj: 35227"
  },
  {
    "caption": "C. Yb Y23A and F129A mutants (green) impaired Yb body formation. Nuclei are shown in blue. Scale bar: 5 μm.",
    "ncbi_link": "Yb: 31262"
  },
  {
    "caption": "D. Yb Y23A and F129A mutants failed to produce flam-piRNAs. miR-310 was used as a loading control.",
    "ncbi_link": "Yb: 31262
flam: 26067356
miR-310: 12798126"
  },
  {
    "caption": "E. Mapping of flam- and tj-piRNAs produced in the flamKG mutant and heterozygote ovaries.",
    "ncbi_link": "flam: 26067356
tj: 35227"
  },
  {
    "caption": "D Clearance of damaged lysosomes depends on p97. Cells were transfected with control (Ctrl) or p97 siRNA oligos, fixed at indicated time points after LLOMe washout and stained for endogenous Gal3. Quantification of the number of Gal3-positive vesicles per cell. Data represent mean ± SD of four independent experiments with ≥30 cells quantified per condition (one-sided Welch's unequal variances t-tests comparing the siCtrl with sip97).",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "F p97 is essential for cell survival after lysosome rupture. Cells were transfected with control (Ctrl), p97 or SEL1L siRNA oligos and treated with indicated concentrations of LLOMe for 12 h. Cell viability was measured using the MTS assay. Data represent mean ± SD of three independent experiments.",
    "ncbi_link": "SEL1L: 6400
p97: 7415"
  },
  {
    "caption": "G Taufibrils are endocytosed and induce lysosomal damage. Taufibrils were generated in vitro, fluorescently labelled by Dylight488 and fragmented by sonication (488-labelled tau). HeLa cells expressing mCherry-Gal3 were incubated with 300 nM taufibrils for 24 h. Arrows indicate compartments that contain 488-labelled tau and are positive for mCherry-Gal3 indicating lysosome rupture. Percentage of cells with Gal3-positive vesicles was quantified from three independent experiments (mean ± SD).",
    "ncbi_link": "Tau: 4137"
  },
  {
    "caption": "H Accumulation of tau-induced lysosomal damage upon p97 depletion. Cells transfected with control (Ctrl) or p97 siRNA oligos were treated as in (G). Percentage of cells with Gal3-positive vesicles was quantified from three independent experiments (mean ± SD). * = p < 0.05; ** = p < 0.01; *** = p < 0.001. Scale bars, 10 µm.",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "A Impaired clearance of damaged lysosomes in cells expressing a p97 disease-mutant. Wild-type and p97R155H/+MEFs were LLOMe-treated for 1 h and released for indicated times. Percentage of cells with Gal3-positive vesicles was quantified from three independent experiments (mean ± SD, Student's unpaired t-test). Scale bar, 25 µm.",
    "ncbi_link": "p97: 269523"
  },
  {
    "caption": "B Stable U2OS cell lines were doxycycline-induced to express myc-tagged p97 wild-type or disease-mutants as indicated. Induced parental cells served as control (U2OS -). Cells were treated with LLOMe for 1h and chased for indicated time before fixation. Percentage of cells with Gal3-positive vesicles was quantified from three independent experiments. Comparable expression levels were verified (see Figure EV2A).",
    "ncbi_link": "p97: 269523"
  },
  {
    "caption": "D Accumulation of damaged lysosomes in affected p97 patient skeletal muscle. Patient biopsies immunostained for Gal3 and caveolin-3 (Cav3). Quantification from 4 random 10X fields for each biopsy and means for controls and patients, respectively. Patients carry p97 mutations R155H (#1-3) or R93C for (#4). Patients #2 and #3 are cousins. Scale bar, 100 µm.",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "A Candidate screen for p97 cofactors involved in autophagy of damaged lysosomes. HeLa cells were transfected with indicated siRNA oligos and LLOMe-treated for 1 h. Cells were chased for 12 h, fixed and stained for Gal3. See Figure EV3 for depletion efficiency.B Quantification of the percentage of cells with more than three Gal3 vesicles per cell for each condition. This threshold was chosen so that less than 1% of untreated cells were considered positive. Data represent mean ± SEM of three independent experiments with ≥30 cells quantified per condition. * = p < 0.05; ** = p < 0.01; *** = p < 0.001 (one-sided Welch's t-tests).",
    "ncbi_link": "p97: 7415"
  },
  {
    "caption": "D An ATP-stabilized complex of p97 containing both UBXD1 and PLAA. Stable HEK293 cell lines were doxycycline-induced to express p97 wild-type (wt) or the ATPase-mutant E578Q (EQ) at near endogenous level. Endogenous UBXD1 was immunoprecipitated and associated proteins detected by immunoblotting with indicated antibodies. Arrowheads indicate endogenous (lower band) and induced p97 (upper band).",
    "ncbi_link": "p97: 269523"
  },
  {
    "caption": "E Stable HEK293 cells treated as in (D) and transiently expressing GFP-tagged YOD1-wt or the YOD1-C160S catalytic mutant (CS) were processed for co-immunoprecipitation with GFP nanobodies. Asterisk, unspecific band. Note that the YOD1-CS mutant stabilized p97 binding and, in the p97-EQ background, also associated with UBXD1 and PLAA.",
    "ncbi_link": "p97: 269523
YOD1: 55432"
  },
  {
    "caption": "C Cells expressing GFP-p97-EQ were treated as in (A) and stained with antibodies as indicated.D Quantification of the total number of K63- or K48-ubiquitinated vesicles per cell, and number of p97-EQ positive K63- or K48-ubiquitinated vesicles (mean ± SD).E Percentage of GFP-p97-EQ vesicles positive for K63 or K48 chains was determined (mean ± SD).",
    "ncbi_link": "p97: 269523"
  },
  {
    "caption": "A Time course of K63- and K48-ubiquitination. Control-depleted cells were fixed at indicated time points after LLOMe washout and stained with chain-specific antibodies and LAMP1. Automated quantification of LAMP1 vesicles positive for K63 or K48 chains. Data represent mean ± SD of three independent experiments.B Depletion of p97 or YOD1 results in increase and persistence of K48 chains on damaged lysosomes. Experiment and quantification as in (A) in cells treated with p97 or YOD1 siRNA oligos.",
    "ncbi_link": "p97: 7415
YOD1: 55432"
  },
  {
    "caption": "C The p97-EQ mutant stabilizes K48-conjugates. Lysosome damage was induced as in (A) in cells transfected with GFP-tagged p97-wt or p97-EQ. Cells were chased after washout for 12 h and stained for K48 chains.D Quantification of K48-positive lysosomes 2 h and 12 h after damage in cells treated as in (A). Data represent mean ± SD of three independent experiments.",
    "ncbi_link": "p97: 269523"
  },
  {
    "caption": "E The catalytically-inactive mutant of YOD1 stabilizes K48-conjugates. Cells transfected with GFP-tagged YOD1-wt or the YOD1-CS were treated and stained as in (C).F Quantification as in (D) of cells treated as in (E). ** = p < 0.01 *** = p < 0.001 (Student's unpaired t-test). ns, not significant. Scale bars, 10 µm.",
    "ncbi_link": "YOD1: 55432"
  },
  {
    "caption": "A YOD1 can link p97 to ubiquitin. Ubiquitin-GST (Ub-GST) or GST alone was incubated with the indicated purified proteins and isolated. Co-isolated proteins (pulldown) were detected in SDS-gels. Note binding of p97 and YOD1 to Ub-GST only in combination.",
    "ncbi_link": "p97: 269523
YOD1: 55432"
  },
  {
    "caption": "B The S2 site of YOD1 is critical for ubiquitin binding. Experiments as in (A) with indicated combinations of p97 and YOD1-wt or the ubiquitin-binding mutant, MutS2.",
    "ncbi_link": "YOD1: 55432"
  },
  {
    "caption": "C Reconstitution of a complex of ELDR components on ubiquitin. Experiments as in (A) with combinations of p97-wt or p97-EQ, YOD1, PLAA and UBXD1 as indicated. Note that PLAA associates with p97 and YOD1 on ubiquitin only in the case of p97-EQ.",
    "ncbi_link": "PLAA: 9373
UBXD1: 80700
p97: 269523
YOD1: 55432"
  },
  {
    "caption": "D Translocation of YOD1 to lysosomes depends on ubiquitin binding by the S2 site. LLOMe-treated cells expressing GFP-YOD1-CS or the double mutant GFP-YOD1-CS-MutS2 were chased for 2 h and stained for K48 chains and LAMP1. Ratio of GFP signal on K48 vesicles to GFP signal in the whole cell was determined.",
    "ncbi_link": "YOD1: 55432"
  },
  {
    "caption": "E The S2 site is essential for K48-conjugate removal. GFP-YOD1-wt or GFP-YOD1-MutS2 overexpressing cells treated as in (D) were stained for K48 chains. Quantification of the number of K48-positive vesicles per cell. Data represent mean ± SD of three independent experiments. ** = p < 0.01 (Student's unpaired t-test). Scale bars, 10 µm.",
    "ncbi_link": "YOD1: 55432"
  },
  {
    "caption": "E Depletion of ELDR components impairs LC3 recruitment for autophagosome formation. Cells were transfected with control (Ctrl), p97 or YOD1 siRNA oligos, treated with LLOMe, fixed after 12 h chase and stained for endogenous LC3 and K48 chains. Quantification of the number of K48-positive vesicles per cell and number of LC3-positive K48 vesicles per cell was determined. Data represent mean ± SD of three independent experiments. Scale bars, 10 µm.",
    "ncbi_link": "p97: 7415
YOD1: 55432"
  },
  {
    "caption": "(D) The indicated amounts of recombinant wild-type and mutant PPM1H or PPM1J (with a His-Sumo N-terminal tag, expressed in E. coli) were incubated in vitro with 2.5 µg pThr72 phosphorylated Rab8a (left) or pThr73 phosphorylated Rab10 (right) for 20 min in the presence of 10 mM MgCl2 in 40 mM HEPES pH 7.5 buffer. Reactions were terminated by addition of SDS Sample Buffer and analyzed by Phos-tag gel electrophoresis that separates phosphorylated (slow migrating) and dephosphorylated Rabs. The gel was stained with Instant Blue Coomassie. D288A is a substrate-trapping (inactive) variant of PPM1H and was used as a control.",
    "ncbi_link": "His: 
PPM1H: 57460
PPM1J: 333926"
  },
  {
    "caption": "(B) In vitro malachite green assay time course of recombinant PPM1H mutants against 16 μM pThr72 phosphorylated Rab8a protein (GTPγS, left), 32 μM pThr72 phosphorylated Rab8a peptide (middle), or 32 μM pThr73 phosphorylated Rab10 peptide (right). The experiments were repeated 4 times. The error bars represent SE of mean of the technical replicates.",
    "ncbi_link": "PPM1H: 57460"
  },
  {
    "caption": "I) In utero electroporation of cortical  tissue of shRNA against DOT1L   and control alongside a GFP  expressing plasmid, followed by assessment of expression  of CTIP2  and TUBB3  as markers for neuronal differentiation  to study cell-autonomous and non-autonomous effects. Scale bars: 20 µm. Dotted lines mark either ventricular   or pial   surface of tissue slide. J) Quantification of CTIP2-, and TUBB3-positive cells in VZ, SVZ, IZ, and CP  in control and shDot1l  sections. Total n of independent experiments: 6 (n=3 control shRNA, n=3 shDot1l ). T-test was performed, *p<0.05, error bars represent SEM.",
    "ncbi_link": "GFP: 
Dot1l: 208266
DOT1L: 208266"
  },
  {
    "caption": "C) Quantification of microinjected cells found as single-cell or two-cells clusters, expressed as percentage of total Dx-A555-positive cells per condition. D) Quantification of microinjected cells with or without contact to the apical  surface of the organotypic slice expressed as percentage of total  Dx-A555-positive cells per condition. Total n of independent microinjection experiments: 6 (n=3 wild type embryos, n=3 in Tis21-GFP embryos). Total number of cells scored: Con, 156 cells; EPZ, 287 cells. E) EOMES-positive and EOMES-negative cells plotted as a percentage of total cells scored per condition. F) TUBB3-positive and TUBB3-negative cells in control and EPZ  conditions plotted as a percentage of total cells scored per condition. Data information: Cell scoring based on TUBB3  or EOMES expression  are from three independent experiments (n=3; Con: 70 cells, EPZ: 113 cells). Fisher's exact test was performed for all quantifications, ***p<0.001, error bars represent SEM. MIP - maximum intensity projection.",
    "ncbi_link": "GFP: 
Tis21: 12227"
  },
  {
    "caption": "D) ChIP-seq and ATAC-seq  tracks showing distribution of peaks for selected chromatin  marks on the Asns  locus for NPCs  and cerebral cortex  of E12.5 and E14.5 mice. Tracks for control and EPZ  conditions are compared in NPCs. Indicated is the TSS of Asns.",
    "ncbi_link": "Asns: 27053"
  },
  {
    "caption": "F) ChIP-qPCR  analysis for DOT1L  and IgG (n=7; biological replicates) at the TSS on Asns  genomic locus in in vitro-derived NPCs. One-sided paired Wilcoxon statistical test was performed, error bars represent SEM. **p<0.01. G) ChIP-qPCR  analyses for EZH2  (n=5; biological replicates) and H3K27me3 (n=9; biological replicates) at the TSS on Asns  genomic locus in control and EPZ  treated condition of in vitro-derived NPCs. One-sided paired Wilcoxon statistical test was performed, error bars represent SEM. *p<0.04.",
    "ncbi_link": "Asns: 27053"
  },
  {
    "caption": "C) Ex utero electroporated cells expressing GFP  (green) or TUBB3  (magenta) in control (Con; pCMV-GFP) or in ASNS  overexpression (ASNS  OE; pCMV-ASNS-GFP) condition 24 h after slice culture. Scale bars: 20 µm. Dotted lines mark ventricular  surface of the tissue. Magnifications on the right show exemplarily a GFP and TUBB3  double positive cell upon ASNS  overexpression. Dotted shapes indicate the border of cell soma  based on GFP expression. D) Fraction of TUBB3-positive and -negative cells expressed as percentage of total cells in Con and upon ASNS  OE. Quantifications were made from independent experiments (n=3). Student's t-test, **p<0.01, error bars represent SEM.",
    "ncbi_link": "GFP: 
ASNS: 27053"
  },
  {
    "caption": "E) Representative images of mCherry  (red) or TBR1-expressing (green) cells in control (Con; pCAG-mCherry) or in ASNS  overexpression (ASNS  OE; pCAG-ASNS) condition, 48 h after in utero electroporation. Scale bars: 20 µm. Dotted lines mark ventricular  surface of the tissue. Magnifications on the right show exemplarily mCherry  and TBR1  double or single positive cells upon ASNS  overexpression. F) Fraction of TBR1-positive and -negative cells expressed as percentage of total cells in Con and upon ASNS  OE. Quantifications were made from 1141 cells in control group and 606 cells in ASNS  OE group. Fisher's exact test, ****p<0.0001.",
    "ncbi_link": "mCherry: 
ASNS: 945555"
  },
  {
    "caption": "A) Representative immunofluorescence images showing incorporation of exogenous Myc-CENP-A at centromeres. Sperm nuclei were incubated in M18BP1-depleted interphase Xenopus egg extracts complemented with the indicated M18BP1-1 protein. Extracts were supplemented with RNA encoding Myc-CENP-A to track new CENP-A assembly and in vitro translated HJURP. Scale bar, 10 μm. Insets are magnified 3X. B) Quantification of Myc-CENP-A loading at Xenopus sperm centromeres in (A). Values are normalized to the centromere signals in mock-depleted extract. Dashed lines indicate the Myc-CENP-A assembly signal observed upon M18BP1 depletion (bottom) and Flag-M18BP1-1WT add-back (top) as points of reference for mutant rescue. Graph shows the mean ± SEM of four independent experiments. ",
    "ncbi_link": "Myc: 
CENP-A: 735079"
  },
  {
    "caption": "(A) Translocation of ectopically expressed mCherry-hGBP1 to cytosolic GFP+ S. flexneri ΔipaH9.8 in HeLa hGBP1-KO cells was monitored by time-lapse microscopy. Individual time frames of Movie EV1 starting at 55 min post infection (mpi) are shown.",
    "ncbi_link": "GFP: 
hGBP1: 2633
ipaH9.8: 13917118"
  },
  {
    "caption": "(B) Time-lapse microscopy of fixed GFP+ co-isogenic S. flexneri wild type and rfaL mutant after adding 10 µM Alexa-Fluor647-hGBP1F and 2 mM GTP. Bacteria bound by hGBP1F at 5 min and hGBP1F-enclosed bacteria after 60 min were quantified. Combined data from three independent experiments are shown as mean ± SEM. Significance was determined by unpaired t-tests, two-tailed. n.s., not significant; ****, P ≤ 0.0001.",
    "ncbi_link": "rfaL: 1026218"
  },
  {
    "caption": "(C) Scanning-electron micrographs of live wild type and rfaL mutant strains incubated with no protein or with 5 µM of hGBP1F in the presence of 2 mM GTP for 4 min. Arrowheads point to unattached hGBP1 polymers, arrows point to hGBP1 polymers attached to bacteria, and asterisks mark polymeric structures that appear to fuse with bacterial surfaces",
    "ncbi_link": "rfaL: 1026218"
  },
  {
    "caption": "(E) Confocal images of formaldehyde fixed, co-isogenic GFP+ wild type and mutant S. flexneri strains harboring rfb regions of E. coli serotypes O8 and O25 after 60 min of incubation time in the presence of 10 µM Alexa-Fluor647-hGBP1F and 2 mM GTP.",
    "ncbi_link": "rfb: "
  },
  {
    "caption": "(D) IFNγ-primed wild type and hGBP1-KO HeLa cells stably expressing inactive mutant YFP-Caspase-4C258S were infected with either cytosol-entering S. enterica Typhimurium mutant ΔsifA (MOI = 25) or with S. flexneri ΔospC3ΔipaH9.8 (MOI = 6), a mutant strain lacking Caspase-4 antagonist OspC3 as well as hGBP1 antagonist IpaH9.8. Cells were fixed at 4 hpi (ST ΔsifA) or at 2 hpi (Sf ΔospC3ΔipaH9.8) and stained for endogenous hGBP1. YFP-Caspase-4C258S associated bacteria were quantified and mean ± SEM of combined data from three independent experiments are shown. Significance was determined by two-way ANOVA with Tukey's multiple comparison test. ****, P ≤ 0.0001.",
    "ncbi_link": "YFP: 
Caspase-4: 837
hGBP1: 2633
ipaH9.8: 13917118
IpaH9.8: 13917118
ospC3: 13917033
OspC3: 13917033
sifA: 1252742"
  },
  {
    "caption": "(B Cells were infected with poly-D-lysine treated GFP+ S. flexneri strains at an MOI of 6. Cells were stained for indicated proteins and Z-stacks were recorded using confocal fluorescence microscopy. Actin tails were classified as tails when ≥ 2.5 µm. All graphs show mean values ± SEM of combined data from three independent experiments. All scale bars are 5 µm. Arrows point to bacteria associated with indicated proteins, arrowheads point to bacteria lacking indicated proteins, and asterisks mark bacteria lacking unipolar IcsA localization. (B) Unprimed HeLa cells were infected with wild type or rfaL S. flexneri. Total and unipolar localization of IcsA as well as the actin tail formation were quantified at 1 hpi. Significance was determined by unpaired two-tailed t-tests. n.s., not significant; *, P ≤ 0.05; **, P ≤ 0.01.",
    "ncbi_link": "rfaL: 1026218"
  },
  {
    "caption": "Cells were infected with poly-D-lysine treated GFP+ S. flexneri strains at an MOI of 6. Cells were stained for indicated proteins and Z-stacks were recorded using confocal fluorescence microscopy. Actin tails were classified as tails when ≥ 2.5 µm. All graphs show mean values ± SEM of combined data from three independent experiments. All scale bars are 5 µm. Arrows point to bacteria associated with indicated proteins, arrowheads point to bacteria lacking indicated proteins, and asterisks mark bacteria lacking unipolar IcsA localization. (C- mCherry-hGBP1 was expressed in HeLa hGBP1-KO cells infected with S. flexneri ΔipaH9.8 and stained for IcsA, N-WASP Significance was determined by unpaired t-tests, two-tailed. n.s., not significant; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.",
    "ncbi_link": "hGBP1: 2633
ipaH9.8: 13917118"
  },
  {
    "caption": "Cells were infected with poly-D-lysine treated GFP+ S. flexneri strains at an MOI of 6. Cells were stained for indicated proteins and Z-stacks were recorded using confocal fluorescence microscopy. Actin tails were classified as tails when ≥ 2.5 µm. All graphs show mean values ± SEM of combined data from three independent experiments. All scale bars are 5 µm. Arrows point to bacteria associated with indicated proteins, arrowheads point to bacteria lacking indicated proteins, and asterisks mark bacteria lacking unipolar IcsA localization. D) mCherry-hGBP1 was expressed in HeLa hGBP1-KO cells infected with S. flexneri ΔipaH9.8 and stained for Arp2, and F-actin at 2.5 hpi. Significance was determined by unpaired t-tests, two-tailed. n.s., not significant; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.",
    "ncbi_link": "mCherry: 
hGBP1: 2633
ipaH9.8: 13917118"
  },
  {
    "caption": "Cells were infected with poly-D-lysine treated GFP+ S. flexneri strains at an MOI of 6. Cells were stained for indicated proteins and Z-stacks were recorded using confocal fluorescence microscopy. Actin tails were classified as tails when ≥ 2.5 µm. All graphs show mean values ± SEM of combined data from three independent experiments. All scale bars are 5 µm. Arrows point to bacteria associated with indicated proteins, arrowheads point to bacteria lacking indicated proteins, and asterisks mark bacteria lacking unipolar IcsA localization. (E) IFNγ-primed and unprimed wild type and hGBP1-KO HeLa cells were infected with S. flexneri ΔipaH9.8 and subcellular localization of IcsA, N-WASP, Arp2, and F-actin was assessed and quantified at 2.5 hpi. Significance was determined by two-way ANOVA with Tukey's multiple comparison test. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001.",
    "ncbi_link": "hGBP1: 2633
ipaH9.8: 13917118"
  },
  {
    "caption": "(A) Immunohistochemistry  of Bcl6 (red), Cux1  (green), and Satb2  (blue) in P2 Bcl11aF/F;Emx1IRESCre and control neocortex. Nuclei  are stained  with Dapi  (white). (B) Relative quantification of Bcl6+, Satb2+, and Cux1+ cells in Bcl11aF/F;Emx1IRESCre and control neocortex  (n = 4). (C) Numbers of Cux1+ or Satb2+ cells that coexpress Bcl6  are reduced in Bcl11aF/F;Emx1IRESCre compared to control neocortex  (n = 4). Data information: All graphs represent the mean ± s.e.m.; Student's t test; *** p < 0.001. Scale bar, 50 µm.",
    "ncbi_link": "Bcl11a: 14025
Cre: 2777477
Emx1: 13796"
  },
  {
    "caption": "(C-E) Immunohistochemistry  of electroporated P2 Bcl11aF/F neurons  in superficial cortical  layers with GFP  (green) and Bcl6  (red, C), Cux1  (red, D), or Satb2  (red, E) antibodies. Bcl6 expression  is specifically downregulated Bcl11aF/F neocortex  upon electroporation of CAG-CreGFP in comparison to CAG-CtlGFP control plasmid. Nuclei  are stained  with Dapi  (white). Data information: White arrowheads point at GFP+ cells that also express Bcl6, Cux1, Satb2  indicate cells expressing only GFP+. Scale bars, 20 µm (C-E),",
    "ncbi_link": "GFP: 
Bcl11a: 14025
Cre: 2777477"
  },
  {
    "caption": "(H) Immunohistochemistry  of electroporated P5 Bcl11a∆/F and Bcl11a+/F neurons  in superficial cortical  layers with GFP  (green) and cleaved caspase 3 (CC3, magenta) antibodies. Electroporation of Neurod-CreGFP plasmid together with CAG-LSL-Bcl6GFP into Bcl11aF/F neocortex  reduces the number of CC3+ cells to control levels. (I) Quantification of the experiment shown in (H) (n = 4). Results are expressed as mean ± s.e.m.; one-way ANOVA followed by Tukey's post hoc test; *** p < 0.001. Data information: White arrowheads point at GFP+ cells that express CC3. Black arrowheads indicate cells expressing only GFP+. Scale bars, , 50 µm (H).",
    "ncbi_link": "GFP: 
Bcl11a: 14025
Bcl6: 12053
Cre: 2777477
Neurod: 18012"
  },
  {
    "caption": "(A) Immunohistochemistry  of cleaved caspase 3 (CC3) shows that the number of CC3+ cells (marked by black arrowheads) is increased in P5  Bcl6F/F;NexCre  compared to control neocortex. Insets are enlargements of the boxed areas in corresponding panels. Data information: Scale bars, 500 µm (A)",
    "ncbi_link": "Bcl6: 12053
Cre: 2777477
Nex: 11922"
  },
  {
    "caption": "(J) Immunohistochemistry  of electroporated P5 Bcl11aF/F neurons  in superficial cortical  layers with GFP  (green) and cleaved caspase 3  (CC3, magenta) antibodies. Electroporation of CAG-CreGFP plasmid together with Foxo1-shRNAGFP#4 into Bcl11aF/F neocortex  reduces the number of CC3+ cells to control levels. White and black arrowheads indicate GFP+ CC3+ and GFP+ cells, respectively. (K) Quantification of the experiment shown in (J) (n = 4, CAG-CtlGFP/Ctl-shRNAGFP; n = 3, CAG-CreGFP/Ctl-shRNAGFP; n = 5, CAG-CreGFP/Foxo1-shRNAGFP#4). Results are expressed as mean ± s.e.m.; one-way ANOVA followed by Tukey's post hoc test; * p < 0.05. Data information: Scale bars, , 50 µm J).",
    "ncbi_link": "GFP: 
Bcl11a: 14025
Cre: 2777477
Foxo1: 56458"
  },
  {
    "caption": "B) Co-immunoprecipitation  analysis to elucidate the  interaction between Suv39h1 and   HP1. Whole-cell extracts of HEK293T  cells expressing 3xFlag-Suv39h1 or 3xFlag-ΔN-Suv39h1 were subjected to  immunoprecipitation  with the anti-Flag tag antibody followed by immunoblotting  with the indicated antibodies. IgG represents the heavy or light chain",
    "ncbi_link": "Flag: 
Suv39h1: 6839"
  },
  {
    "caption": "F) Co-immunoprecipitation analysis to elucidate the interaction between  Setdb1  and  HP1. Whole-cell extracts of  HEK293T cells expressing 3xFlag-Setdb1  or 3xFlag-Setdb1 mutants were subjected to immunoprecipitation  with the anti-HP1β antibody The immunocomplex was analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "Flag: 
Setdb1: 9869"
  },
  {
    "caption": "G)  Protein decay analysis of HP1 interaction-defective  Setdb1  mutant. mESC lines stably expressing 3xFlag-Setdb1 or 3xFlag-Setdb1-3A were treated with CHX and MG132 for the indicated  times. Stacked bar plots show the summarized protein amounts of Setdb1 (right). Data represented as mean ± SD (n = 4, biological replicates). **p < 0.01 (Tukey's honestly significant difference test).",
    "ncbi_link": "Flag: 
Setdb1: 84505"
  },
  {
    "caption": "B)  Protein expression levels of H3K9 MTs and  histone  modification levels in HP1-cTKO cells were monitored by  immunoblotting. The intensities were quantified using ImageJ software and summarized on the right. The thin gray line and bold colored line show individual data and means of the experimental replicates (n ≥ 3, biological replicates), respectively.",
    "ncbi_link": "HP1: 10951"
  },
  {
    "caption": "C) Comparison of H3K9me3 levels between HP1-deficient cells and Suv39h/Setdb1-deficient cells. H3K9me levels were quantified using ImageJ software and are summarized at the bottom; the horizontal line represents the mean intensity of each cell. More than 75 nuclei were counted for each staining. **p < 0.01 (Tukey's honestly significant difference test).",
    "ncbi_link": "HP1: 12417///12419///12412
Setdb1: 84505
Suv39h: 64707///20937"
  },
  {
    "caption": "D)  Electron microscopy  images of HP1-cTKO cells in the absence of 4OHT (left) and of cells treated with 4OHT  for 4 days (right). Boxes represent enlarged images.",
    "ncbi_link": "HP1: 10951"
  },
  {
    "caption": "B) Subcellular distribution of H3K9 MTs in the HP1-cTKO cells was examined by  immunoblotting. α-Tubulin, Ezh2, and  histone H3  were used as representative markers for each fraction. Stacked bar plots show the abundance ratios of H3K9 MTs among the three fractions (right).",
    "ncbi_link": "HP1: 10951"
  },
  {
    "caption": "B, Elucidation of protein-protein interaction between HP1  and H3K9 MTs by co-immunoprecipitation  analysis. Whole-cell extracts of HEK293T cells co-expressing HA-HP1β  mutants and epitope-tagged proteins of interest were subjected to  immunoprecipitation with the anti-HA  tag antibody. The immunocomplex was analyzed by  immunoblotting  with the indicated antibodies. The intensities were quantified using ImageJ software, normalized, and shown on the top.",
    "ncbi_link": "HA: 
HP1β: 10951"
  },
  {
    "caption": "E) Evaluation of HP1β  mutants for maintaining H3K9me2/3 and ensuring protein stability of  H3K9 MTs. H3K9me2/3 levels and protein levels of H3K9 MTs in  HP1-cTKO lines expressing 3xFlag-hHP1β mutants were compared before and after 4OHT  treatment. The intensities were quantified with ImageJ software and are summarized on the right. Data represented as mean ± SD (n > 3, biological replicates). *p < 0.05, **p < 0.01 (Welch's test).",
    "ncbi_link": "Flag: 
HP1: 10951
HP1β: 10951"
  },
  {
    "caption": "B) Protein expression levels of Jmjd1a/b in  HP1-cTKO cells were monitored by  immunoblotting. The intensities were quantified using ImageJ software and summarized on the right. The thin gray line and bold colored line show individual data and the mean of experimental replicates, respectively.",
    "ncbi_link": "HP1: 10951"
  },
  {
    "caption": "C) Evaluation of  HP1β mutants for ensuring protein stability of Jmjd1a/b. Protein levels of Jmjd1a/b in  HP1-cTKO lines expressing 3xFlag-hHP1β mutants were compared before and after  4OHT  treatment. The intensities were quantified with ImageJ software and are summarized on the right. Data represented as mean ± SD (n > 3, biological replicates). *p < 0.05, **p < 0.01 (Welch's test).",
    "ncbi_link": "Flag: 
HP1: 10951
HP1β: 10951"
  },
  {
    "caption": "C) Impact of Suv39h/Setdb1/G9a depletion on HP1-mediated protein stability regulation of  Jmjd1a/b. Jmjd1a/b were destabilized in mESCs lacking Suv39h/Setdb1/G9a, even though HP1  was present.",
    "ncbi_link": "G9a: 110147
Setdb1: 84505
Suv39h: 64707///20937"
  },
  {
    "caption": "D) Functional evaluation of  H3K9me2/3 for confining  HP1 to chromatin. Subcellular  localizations of HP1α, β and γ in TT2 and mESCs lacking Suv39h/Setdb1/G9a were compared. α-Tubulin, Ezh2, and  histone H3 were used as representative markers for each fraction.",
    "ncbi_link": "G9a: 110147
Setdb1: 84505
Suv39h: 20937///64707"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0, snc1, and two independent transgenic lines of SNIPER1 OE into snc1 background. OE stands for overexpression of SNIPER1. Scale bar = 1 cm. SNIPER1 gene expression in the indicated plants as determined by RT-PCR. Error bars represent mean ± SD (n = 3). Two independent experiments were carried out with similar results. Quantification of H.a. Noco2 sporulation in the indicated genotypes 7 days post inoculation (dpi) with 105 spores per ml water. Error bars represent mean ± SD (n=4). Three independent experiments were carried out with similar results. Growth of P.s.m. ES4326 on four-week-old leaves of the indicated genotypes at 0 and 3 dpi with bacterial inoculum of OD600 = 0.001. Error bars represent mean ± SD (n=4 for day 0; n=5 for day 3). Three independent experiments were carried out with similar results.",
    "ncbi_link": "SNIPER1: 837980
snc1: 827397"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of two independent transgenic lines of SNIPER1 OE in Col-0 background. Scale bar = 1 cm. No difference in growth and development was observed. SNIPER1 gene expression in the indicated plants as determined by RT-PCR. Error bars represent mean ± SD (n = 3). Two independent experiments were carried out with similar results. Quantification of H.a. Noco2 sporulation in the indicated genotypes 7 days post inoculation (dpi) with 105 spores per ml water. Error bars represent mean ± SD (n=4). Three independent experiments were carried out with similar results. Growth of P.s.t. DC3000 on four-week-old leaves of the indicated genotypes at 0 and 3 dpi with bacterial inoculum of OD600 = 0.001. Error bars represent mean ± SD (n=4 for day 0; n=5 for day 3). Three independent experiments were carried out with similar results.",
    "ncbi_link": "SNIPER1: 837980"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0, chs1-2 (A), chs2-1 (B) and two independent transgenic lines of SNIPER1 OE into chs1-2 (A) and chs2-1 (B) backgrounds. Plants were grown at 16 °C under long day conditions. Scale bar = 1 cm.",
    "ncbi_link": "chs2: 
SNIPER1: 837980
chs1: 838337"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0, chs3-2D (C), snc2-1D eds5 npr1 (D) and two independent transgenic lines of SNIPER1 OE into chs3-2D (C) and snc2-1D eds5 npr1 (D) backgrounds. Scale bar = 1 cm.",
    "ncbi_link": "SNIPER1: 837980
chs3: 831657
eds5: 830058
npr1: 842733
snc2: 827610"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0, mekk1-5 ndr1, and two independent transgenic lines of SNIPER1 OE into mekk1-5 ndr1 background. Scale bar = 1 cm. The mekk1 ndr1 double mutant was used instead of the mekk1-5 single mutant is to overcome the sterility. SNIPER1 gene expression in the indicated plants as determined by RT-PCR. Error bars represent mean ± SD (n = 3). Two independent experiments were carried out with similar results. Quantification of H.a. Noco2 sporulation in the indicated genotypes 7 days post inoculation (dpi) with 105 spores per ml water. Error bars represent mean ± SD (n=4). Three independent experiments were carried out with similar results. Growth of P.s.m. ES4326 on four-week-old leaves of the indicated genotypes at 0 and 3 dpi with bacterial inoculum of OD600 = 0.001. mn stands for mekk1-5 ndr1 double mutant. Error bars represent mean ± SD (n=4). Three independent experiments were carried out with similar results.",
    "ncbi_link": "SNIPER1: 837980
mekk1: 826409
ndr1: 821607"
  },
  {
    "caption": "In vitro ubiquitination assay using E. coli-expressed SNIPER1-myc (E3), AtUBC8 (E2), AtUBA1 (E1) and/or HIS-FLAG-Ubiquitin. The molecular mass markers are indicated on the left (kDa). Asterisk indicates SNIPER1-myc. Arrow points to His-FLAG-Ub and straight lines on the right indicate self-ubiquitinated SNIPER1.",
    "ncbi_link": "SNIPER1: 837980"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0 and two independent transgenic lines of 35S-SNIPER1H129Y. Scale bar = 1 cm.",
    "ncbi_link": "SNIPER1: 837980"
  },
  {
    "caption": "PR1 and PR2 gene expression in the indicated plants as determined by RT-PCR. Error bars represent mean ± SD (n = 3). Two independent experiments were carried out with similar results.",
    "ncbi_link": "PR2: 824893
PR1: 815949"
  },
  {
    "caption": "Morphology of four-week-old soil-grown plants of Col-0, sniper1-1, sniper2-1, eds1-2, SNIPER1H129Y, SNIPER1H129Y eds1-2, sniper1-1 sniper2-1 eds1-2 and sniper1-c1 sniper2-1 eds1-2. sniper1-1 is an exonic T-DNA insertional mutant. sniper1-c1 is a SNIPER1 knockout mutant containing 807bp deletion that was generated by CRISPR-Cas9 system. Scale bar = 1 cm.",
    "ncbi_link": "Cas9: 
CRISPR: 
sniper1: 837980
SNIPER1: 837980
sniper2: 839223
eds1: 823964"
  },
  {
    "caption": "Interaction of SNIPER1 H129Y-CLuc and SUMM2NB-NLuc (D), RPP4NB-NLuc (E) or CHS1NB-NLuc (F) as tested by split-luciferase complementary assay in N. benthamiana. Three biological repeats with four technical repeats each were carried out with similar results.",
    "ncbi_link": "CHS1: 
Luc: 
NB: 
RPP4: 
SUMM2: 
SNIPER1: 837980"
  },
  {
    "caption": "1.SARS-CoV-2 activates delayed innate immune responses in lung epithelial cells Measurements of replication and innate immune induction in Calu-3 lung epithelial cells infected with SARS-CoV-2 at MOIs 0.08, 0.4 and 2 TCID50VERO/cell. (A) Replication of SARS-CoV-2 genomic and subgenomic E RNAs (qRT-PCR). (B) Quantification of N staining from cells in (A) by flow cytometry. Mean percentage of N-positive of all live-gated cells is shown +/- SEM, n=2.",
    "ncbi_link": "E RNAs: 43740570"
  },
  {
    "caption": "Fold induction of (F) interferons (IFNβ, IFNλ1 and IFNλ3) pro-inflammatory mediators (IL-6 and CCL5) each overlaid with SARS-CoV-2 E (qRT-PCR).",
    "ncbi_link": "CCL5: 6352
IFNβ: 3456
IFNλ1: 282618
IFNλ3: 282617
IL-6: 3570"
  },
  {
    "caption": "Fold induction of IFN stimulated genes (CXCL10 and IFIT2) each overlaid with SARS-CoV-2 E (qRT-PCR).",
    "ncbi_link": "CXCL10: 3627
IFIT2: 3433"
  },
  {
    "caption": "Peak SARS-CoV-2 replication precedes innate immune activation. (A-I) (A,C) Representative images of NF-κB p65 (A) (red) and IRF3 (C) (red) nuclear localisation in mock or SARS-CoV-2 infected (MOI 0.4 TCID50VERO/cell) Calu-3 cells at 24 hpi. SARS-CoV-2 N protein (green. (E and G) Representative images of IL-6 mRNA (E) detected by FISH (red) and N protein (green) , or IFIT1 mRNA (G) (green) with N protein (red), both with nuclei (DAPI, blue) in mock or SARS-CoV-2 infected (MOI 0.4 TCID50VERO/cell) Calu-3 cells at 24 hpi. (B, D, F, H, I) Single cell analysis time course quantifying the Integrated Nuclear Intensity of NF-κB p65 (B), IRF3 (D) , or overall integrated intensity for IL-6 (F) or IFIT1 (H) mRNA over time in N protein positive cells and N protein negative cells (I). n=2. Kruskal-Wallis test with Dunn's multiple comparison. * (p<0.05), **** (p<0.0001). Scale bar represents 50µM.",
    "ncbi_link": "IFIT1: 3434
IL-6: 3570"
  },
  {
    "caption": "(E-H) Measurement of (E) viral genomic and subgenomic E RNA (F) fold induction of CXCL10, (G) IFIT2 and (H) and IL-6 at 24 hpi, of Calu-3 cells with SARS-CoV-2 (MOI 0.04 TCID50VERO/cell) with Remdesivir treatment (5μM) prior to, at the time of, or 8 h post-infection. Mean +/- SEM, n=3, One way ANOVA with Dunnett's multiple comparisons test to compare to untreated infected condition ('mock'), ** (p<0.01), *** (p<0.001), **** (p<0.0001).",
    "ncbi_link": "CXCL10: 3627
E RNA: 43740570
IFIT2: 3433
IL-6: 3570"
  },
  {
    "caption": "(Q-R) (Q) Viral E RNA and (R) released infectious virus (TCID50VERO/cell) at 24 hpi of infected Calu-3 cells depleted for MAVs, RIG-I or MDA5. Mean +/- SEM, n=3. Each group compared to siCtrl by One Way ANOVA with Dunnett's multiple comparisons test, *, p>0.05, ** (p<0.01), n.s : non significant.",
    "ncbi_link": "RIG-I: 23586
E RNA: 43740570
MDA5: 64135
MAVs: 57506"
  },
  {
    "caption": "(G-H) Viral genomic and subgenomic E RNA at 24 hpi (RT-qPCR) with DMSO or TPCA (G) or Rux (H) treatment. Data information: (A-H) Mean +/- SEM, n=3, statistical comparisons are made by unpaired t test comparing inhibitor-treated to mock-treated SARS-CoV-2 infected conditions at each MOI and each timepoint. * (p<0.05), ** (p<0.01), *** (p<0.001), **** (p<0.0001).",
    "ncbi_link": "E RNA: 43740570"
  },
  {
    "caption": "(B-J) Calu-3 cells were transfected with siRNA targeting MAVS or non-targeting control (siCtrl) (B-D) or treated with DMSO vehicle or inhibitors 10 μM TPCA-1 (E-G) or 2 μM Ruxolitinib (Rux) (H-J) as shown, and were mock-infected or infected with SARS-CoV-2 at MOI 0.04 TCID50VERO/cell. Virus containing conditioned media (CoM) was harvested at 48 hpi. MDM were treated with Calu-3 virus containing CoM for 6 hpi, before washing and measuring MDM gene expression (B, E, H), and MDM activation markers by flowcytometry 48 h later (C,D,F,G,I,J) , plotting relative median fluorescent intensity (MFI) compared to mock-infected siCtrl (C, D) or mock-infected DMSO control (F, G, I, J). Legends in (B), (E) and (H) apply to (C,D), (F,G) and (I,J) respectively. The inhibitors in (E) and (H) were tested side-by-side with the same mock condition. Mean +/- SEM shown, data from 4-6 independent MDM donors is shown. Statistical comparison by two-tailed paired t-test comparing MDM exposed to control infected CoM to siMAVS/inhibitor treated infected CoM. * (p<0.05), ** (p<0.01), *** (p<0.001).",
    "ncbi_link": "MAVS: 57506"
  },
  {
    "caption": "(B) The number of metabolites that change significantly when wild-type yeast and mutants in the predicted target are treated with the indicated drugs at a concentration of 10 µM are shown. Drugs targeting GPR1 are written in black text, with drugs targeting SNF3 and RGT2 written in purple and green respectively. Orange filled bars are predicted antagonists for GPR1.",
    "ncbi_link": "GPR1: 851527
RGT2: 851417
SNF3: 851333"
  },
  {
    "caption": "(C) The levels of trehalose compared to a DMSO treated control are shown for both wild-type yeast and gpr1 strains treated with predicted antagonists for GPR1. The bar height indicates mean values, and error bars indicate the standard deviation of the mean. Asterisks indicate a p-value of less than 0.05 from a two-sided student's T-test (n = 4 biological replicates) when comparing The WT and gpr1 reponses to the drug. Results are representative of 3 independent experiments.",
    "ncbi_link": "gpr1: 851527"
  },
  {
    "caption": "ATG3 and LC3B gene expression pattern in neutrophils after stimulation with PMA or rapamycin. ATG3 mRNA expression analysis (fold) after PMA (2.44±0.78) and rapamycin (RAP: 1.81±0.41) stimulation. LC3B gene alterations (PMA: 4.98±0.59) and rapamycin (RAP: 1.7±0.55). Effect of 3‐MA pre‐treatment, for both stimuli, was also assessed (PMA+3‐MA: ATG3: 1.36±0.64, LC3B: 1.5±0.49 and rapamycin+3‐MA: ATG3: 1.28±0.46, LC3B: 1.24±0.57). No other significant alteration in ATG genes mRNA levels was detected. Representative data of ATG7 mRNA expression analysis after treatment with PMA (1.21±0.42) and rapamycin (0.94±0.64). Data are representative of six independent experiments and presented as mean relative expression±SD. Wilcoxon matched‐pairs test, *p<0.05 and n.s.=not significant compared with control conditions (dot line) as indicated in the figure. Relative expression (folds) of each gene is derived from substitution of DCT values (normalized by GAPDH DCT value) in 2DDCT equation 36.",
    "ncbi_link": "GAPDH: 
ATG3: 64422
ATG7: 10533
LC3B: 81631"
  },
  {
    "caption": "(D) Analysis of LC3B gene expression levels in neutrophils treated with TLR agonists. LPS (bar 1: 2.27±0.43), peptidoglycan (bar 2: 2.07±0.42), LTA (bar 3: 2.1±0.49) and R848 (bar 4: 1.89±0.35) compared with medium−treated control cells. Dotted line represents LC3B mRNA levels of medium-treated control cells. Data are representative of six independent experiments and are presented as mean relative expression±SD. Wilcoxon matched−pairs test, *p<0.05.",
    "ncbi_link": "LC3B: 81631"
  },
  {
    "caption": "(E) Assessment of ATG gene expression levels in PMN after LPS stimulation (50 ng/mL). ATG3 (bar 1: 2.94±0.52), ATG4 (bar 2: 1.72±0.42), ATG5 (bar 3: 1.84±0.34), ATG6 (bar 4: 1.8±0.3), ATG7 (bar 5: 3.13±0.64) and LC3B (bar 6: 2.27±0.43) compared with control cells. Dotted line represents mRNA levels of medium-treated cells. Data are representative of six independent experiments and are presented as mean relative expression±SD. Wilcoxon matched−pairs test, *p<0.05.",
    "ncbi_link": "ATG3: 64422
ATG4: 23192///115201
ATG5: 9474
ATG7: 10533
ATG6: 8678
LC3B: 81631"
  },
  {
    "caption": "Alterations in ATG gene expression after phagocytosis of opsonized E. coli. ATG3 (2.05±0.27), ATG4 (2.20±0.27), ATG5 (2.89±0.42), ATG6 (2.04±0.40), ATG7 (1.98±0.30) and LC3B (2.46±0.39) gene expression (fold) in E. coli‐phagocytosing neutrophils compared with control cells. Dotted line represents mRNA expression levels of control cells. Data are representative of six independent experiments and are presented as mean relative expression±SD Wilcoxon matched‐pairs test, *p<0.05.",
    "ncbi_link": "ATG3: 64422
ATG4: 23192///115201
ATG5: 9474
ATG7: 10533
ATG6: 8678
LC3B: 81631"
  },
  {
    "caption": "A. 293T cells were co-transfected with CMV-renilla, 8X-TBS (eight repeats of the TEAD-binding-sequence) luciferase reporter, Flag-YAP, HA-TEAD2 and wild-type (WT) or catalytically inactive (CS) USP9X-V5. One day after transfection, luciferase activity was measured and normalized with respect to renilla activity. The value for Flag-YAP/HA-TEAD-transfected cells (2nd column) was adjusted to 1. Shown below is a representative Western blot showing that the expression levels were comparable between samples (n=4). Error bars indicate the S.E.M. (*p< 0.05, **p < 0.01; paired Student's t-test).",
    "ncbi_link": "CMV: 
TEAD: 7004///7005///8463///7003
YAP: 10413"
  },
  {
    "caption": "B. 293T cells were transfected with control or USP9X-targeting siRNAs. One day after siRNA transfection, the cells were co-transfected with CMV-renilla, 8X-TBS luciferase, Flag-YAP and HA-TEAD2. Reporter activity was quantified as described in (A) (n=4). Error bars indicate the S.E.M. (***p < 0.001; paired Student's t-test).",
    "ncbi_link": "CMV: 
USP9X: 8239"
  },
  {
    "caption": "D. Cells were treated as described in (C), the indicated mRNAs were analyzed with RT-qPCR, and the results were normalized with respect to the β-actin mRNA (n=4). Error bars indicate the S.E.M. (*p< 0.05, **p < 0.01; paired Student's t-test).",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "E. RPE cells were transfected with the indicated siRNAs for 24 hours, and then co-transfected with CMV-renilla and 8X-TBS luciferase. One day after the latter transfection, the cells were re-seeded to either sparse or dense conditions, and reporter activity was measured at 24 hours after re-seeding (n=3). Error bars indicate the S.E.M. (**p < 0.01; paired Student's t-test).",
    "ncbi_link": "CMV: "
  },
  {
    "caption": "G. Densely cultured RPE cells transduced with CRISPR-SAM targeting USP9X were fractionated into cytosolic and nuclear extracts, and analyzed by Western blotting for the indicated proteins.",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "C. Densely cultured RPE cells transduced with CRISPR-SAM targeting USP9X were analyzed by Western blotting for the indicated proteins.",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "D. RPE or MCF10A cells expressing the control or USP9X shRNA were transfected with the LATS1/2 siRNA as indicated. Cells were re-seeded to low density and harvested after one day.",
    "ncbi_link": "LATS1: 9113
USP9X: 8239"
  },
  {
    "caption": "E. RPE cells transduced with Flag-YAP WT or Flag-YAP 5SA were transfected with the indicated siRNAs. Cells were re-seeded to low density and harvested after one day.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "F. RT-qPCR of CTGF mRNAs in the cells described in (E) (n=3). Error bars indicate the S.E.M. (*p< 0.05, paired Student's t-test).",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "D. RPE cells transduced with Flag-AMOTL2 were transfected with a 1:1 mixture of the two USP9X siRNAs. One day after siRNA transfection, the cells were re-seeded to the sparse condition and an in vivo ubiquitination assay was performed after one day.",
    "ncbi_link": "AMOTL2: 51421
USP9X: 8239"
  },
  {
    "caption": "A. Flag-AMOTL2 constructs were designed to express regions spanning from the N-terminus to the coiled-coil domain (AA 1-306), the coiled-coil domain (AA 307-581), and the C-terminal portion (AA 582-781). These constructs were co-transfected into 293T cells with Myc-Ub, and an in vivo ubiquitination assay was conducted. *, non-specific band.",
    "ncbi_link": "Ub: 6233///7311///7316///7314"
  },
  {
    "caption": "D. RPE or MCF10A cells were transduced with Flag-AMOTL2 WT or Flag-AMOTL2 K347/408R, and immunoprecipitated with an anti-Flag antibody. Immunoprecipitated and WCL samples were analyzed by Western blotting for the indicated proteins.",
    "ncbi_link": "AMOTL2: 51421"
  },
  {
    "caption": "E. RPE or MCF10A cells were transduced with Flag-AMOTL2 WT or Flag-AMOTL2 Y213A, and processed as (D).",
    "ncbi_link": "AMOTL2: 51421"
  },
  {
    "caption": "A. MCF10A cells expressing shRNA against AMOTL2 were complemented with shRNA-resistant Flag-AMOTL2 WT or the K347/408R mutant. The indicated cells were harvested and analyzed by Western blotting for the indicated proteins.",
    "ncbi_link": "AMOTL2: 51421"
  },
  {
    "caption": "F. Lats1 -/-; Lats2 fl/fl; SV40 mouse embryonic fibroblasts complemented with vector, LATS2 WT or ΔUBA mutant were infected with empty (control) or Zeocin-Cre retroviruses and selected with 400 μg/ml of Zeocin for 4 days. Harvested cells were analyzed by Western blotting for the indicated proteins.",
    "ncbi_link": "Cre: 
Lats1: 16798
Lats2: 50523
LATS2: 50523"
  },
  {
    "caption": "A Relative gene expression of IP3R1 (blue), IP3R2 (red), and IP3R3 (green) in IP3R‐silenced DCs. DCs were infected with two lentiviruses encoding for different shRNAs for IP3R isoforms. ShScramble‐infected DCs were used as a control. Gene expression was determined by a quantitative PCR. It was calculated with respect to GAPDH expression and normalized to the levels observed in the shScramble. The median plus standard deviation of three independent experiments are shown.",
    "ncbi_link": "GAPDH: 
IP3R1: 16438
IP3R2: 16439
IP3R3: 16440"
  },
  {
    "caption": "D Relative IP3R2 expression in ShScramble‐infected DCs (gray), shIP3R1 (blue), and IP3R3 (green)‐silenced DCs. The experiment was performed as described in (A).",
    "ncbi_link": "IP3R1: 16438
IP3R2: 16439
IP3R3: 16440"
  },
  {
    "caption": " The 3'-UTR sequence of mUcp1 RNA. Canonical CPEs (UUUUA1-2U in bold), the reported BRF1-binding site (UAUUUAU, gray box) and predicted IMP2-binding motifs (AYAYA and YA2YA, underlined) are denoted. Ucp1L and Ucp1S carrying long and short 3'-UTRs, respectively, are resulted from alternative use of two polyadenylation signals (Hex: AAUAAA, open box). ORF, open reading frame. The arrowhead marks the end of Ucp1S sequence. Northern blots of Ucp1 using 5 µg BAT total RNA and the denoted radiolabeled probes ",
    "ncbi_link": "Ucp1: 22227"
  },
  {
    "caption": " Schematic comparison of mUcp1L and hUcp1. Poly(A) signal (Hex, open box) and CPE (black box) are denoted. The RT-PCR  results from human, WT (Ucp1+/+) and UCP1-KO (Ucp1-/-) BAT RNA samples ",
    "ncbi_link": "Ucp1: 22227
Ucp1: 7350
UCP1: 22227"
  },
  {
    "caption": " Dual luciferase reporter assay and RT-qPCR. The reporter plasmids, Fluc-mUcp1S, -mUcp1L or -hUcp1L 3'-UTR, and Rluc were co-transfected into differentiated HIB1B adipocytes. The transfected cells were used for luciferase activity assay and RT-qPCR. Data are mean ± SD from 3 independent experiments. Translation efficiency was defined as normalized activity (Fluc/Rluc) divided by normalized RNA level (Fluc/Rluc). ***p < 0.001 compared with Fluc-mUcp1S, one-way ANOVA ",
    "ncbi_link": "Fluc: 
Rluc: 
Ucp1: 22227
Ucp1: 7350"
  },
  {
    "caption": " Northern blotting of Ucp1 and 18S rRNA and RT-PCR of Ucp1L and Ucp1S using total RNAs from the denoted BAT samples (2 mice per genotype, 2-3 mo old). The short PCR fragments were isolated for sequencing ",
    "ncbi_link": "rRNA: 
Ucp1: 22227"
  },
  {
    "caption": " Western blot analysis using WT and Ucp1∆L BAT lysates. The protein level of UCP1 was normalized to GAPDH (4 mo old, n = 4 per group). **p < 0.01, Student's t test ",
    "ncbi_link": "Ucp1: 22227"
  },
  {
    "caption": " Dual luciferase reporter assay. The reporter plasmids, Fluc-mUcp1L 3'-UTR, and Rluc were co-transfected with the plasmid expressing EGFP, or myc-tagged CPEB (immunoblots shown at the left) into differentiated HIB1B adipocytes (Data from 3 independent experiments). *p < 0.05 compared with EGFP, one-way ANOVA ",
    "ncbi_link": "CPEB: 
Fluc: 
Rluc: 
Ucp1: 22227"
  },
  {
    "caption": " Western blot analysis using BAT lysates prepared from various CPEB-WT and KO male littermates (4 mo old, n = 4 per group). *p < 0.05, Student's t test ",
    "ncbi_link": "CPEB: "
  },
  {
    "caption": " Northern blotting of Ucp1L and Ucp1S in BAT from CPEB2-WT and -KO male mice at room temperature or after 5-h cold exposure (CE) at 4oC (5 mice per genotype, 4-7 mo old)",
    "ncbi_link": "CPEB2: 231207
Ucp1: 22227"
  },
  {
    "caption": "Western blot analysis of UCP1 and GAPDH in BAT lysates from WT and KO female mice at 4 and 12 mo old (n = 3 per group). Protein levels were normalized to that of GAPDH. RT-qPCR analysis of Ucp1 mRNA level in BAT collected from (B) relative to Gapdh mRNA level",
    "ncbi_link": "Gapdh: 
Ucp1: 22227"
  },
  {
    "caption": "Hematoxylin and eosin sections of BAT from WT and CPEB2-KO female mice at 4 and 12 mo old. Scale bars, 1 mm",
    "ncbi_link": "CPEB2: 231207"
  },
  {
    "caption": " CPEB2-WT and -KO mice were transduced with adeno-associated virus (AAV) expressing full-length (AAV_CP2) or RNA-binding domain (AAV_RBD) of CPEB2. Immunostaining of CPEB2 and UCP1 in KO BAT transduced with AAV_CP2 for 2 weeks, with Hoechst staining of nuclei. Scale bar, 10 µm. See more images in Fig EV4D ",
    "ncbi_link": "CPEB2: 231207"
  },
  {
    "caption": "b) Box plot showing the distribution of log2(FC) of all or selected miR-29a targets in the Data ref: Mazziotti et al, 2017 dataset of age-regulated genes in the visual cortex. Notches represent confidence intervals for the median. Whiskers indicate 95th and 5th percentile, the box marks the 25th and 75th percentile. Significance vs. all detected genes was assessed by Wilcoxon's test (miR-29a targets p=4.9x10-14, top 200 miR-29a targets p=3.7x10-38).",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "(d,e) Mature miR-29a (n=3/4 mice for each age; one-way ANOVA, p<0.0001; post hoc Tukey's test ***p<0.001, ****p<0.0001, ns not significant) and Dnmt3a expression level (normalized to P10) at different ages measured by qPCR (n=3/4 mice for each age; one-way ANOVA, p<0.0001; post hoc Tukey's test: *p<0.05, **p<0.01, ****p<0.0001, ns not significant). One way ANOVA p-values are reported. Error bars represent ±SEM. f) Scatter plot showing correlation of miR-29a and Dnmt3a levels in the visual cortex display a strong negative correlation (Pearson correlation: r=-0.817, p<0.001). Each circle represents data from a single animal. ",
    "ncbi_link": "Dnmt3a: 13435
miR-29a: 387222"
  },
  {
    "caption": "g) Representative examples of in situ hybridization on visual cortex (left P25, right P120) using a LNA probe against miR-29a. Scale bar 180 µm. Cortical layers are delimited by roman numerals and brackets",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "h) Example of co-staining for PV (green), miR-29a (red) and nuclear marker (blue) in a P120 mouse. White triangles represent PV+/miR-29a+ cells. Scale bar 20 µm.",
    "ncbi_link": "miR-29a: "
  },
  {
    "caption": "Mature miR-29a expression (miR29) in visually deprived mice: a) normal rearing (NR, N=5) vs dark rearing (DRb, N=5); t-test, p=0.19, b) NR (N=4) vs dark rearing from P10 (DRp10, N=5; t-test, p=0.70. In both experiments, analysis was performed at P25",
    "ncbi_link": "miR-29a: 387222
miR29: 387222"
  },
  {
    "caption": "Mature miR-29a expression (miR29) in visually deprived mice: c) one week period of dark rearing beginning at P30 (DRw) followed by a 4 hour exposure to light (DRw+4h light) vs control animals (ctr, N=4 for each group; one-way ANOVA, p=0.68)",
    "ncbi_link": "miR-29a: 387222
miR29: 387222"
  },
  {
    "caption": "Mature miR-29a expression (miR29) in visually deprived mice: d) days of MD beginning at P25, contralateral cortex vs ipsilateral cortex to deprived eye, N=5; paired t test, p=0.52). Error bars represent ±SEM, symbols represent individual cases.",
    "ncbi_link": "miR-29a: 387222
miR29: 387222"
  },
  {
    "caption": "b) MiR-29a and Dnmt3a expression in the cortex treated with scrambled or miR-29a mimic (N=3 mice). Data were normalized to the untreated cortex of the same animal. Mir-29a: scr vs mim29a, t-test, p=0.005; Dnmt3a scr vs mim29a t-test, p<0.0001.",
    "ncbi_link": "Dnmt3a: 13435
MiR-29a: 387222
miR-29a: 387222
Mir-29a: 387222"
  },
  {
    "caption": "c) IOS analysis. Ocular dominance index (ODI) of deprived animals treated with scrambled (scr, N=6 black lines) or miR-29a mimic (mimic29, N=8 orange lines), or left untreated (MD no treat, N=5 grey lines) before and after 3 days of MD. Dashed lines represent single animals, continuous lines the group average. two-way ANOVA RM, treatment X time, p= 0.028; post hoc Sidak's comparison, post-MD mim29a vs scr p<0.05, mim29a vs MD no treat p<0.01; pre-MD scr vs post-MD scr p<0.001; pre-MD MD no treat vs post-MD MD no treat p<0.01; other comparisons not significant).",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "d) The effects of MD on expression of Npas IV and Bdnf exIV is reported as ratio between expression level of deprived and nondeprived cortex for animals treated with scrambled (scr+MD) and miR-29a mimic (mim29a+MD). Each symbol represents the result of a single mouse. (MD+scr vs MD+mim29a; N=4; t-test, Npas4: p=0.038; Bdnf exIV: p=0.049).",
    "ncbi_link": "Bdnf: 12064
miR-29a: 387222
Npas IV: 225872
Npas4: 225872"
  },
  {
    "caption": "b) Effects of amiR-29a on the expression of miR-29a and Dnmt3a. Fold change values with respect to the contralateral untreated cortex are reported (±SEM) for mice treated with amiR-29a or scr. scr vs amiR-29a; N=3 t-test, miR-29a **p=0.0010; Dnmt3a ****p=0.0019.",
    "ncbi_link": "Dnmt3a: 13435
miR-29a: 387222"
  },
  {
    "caption": "c) Distribution of log2(FC) for the significant cases in transcriptomics (N=4 scr treated and N=3 amiR-29a treated biological replicates) and proteomics (N=4 biological replicates per group) datasets of animals treated with amiR-29a versus scr animals. The black line represents the average. (d,e) Box plot showing distribution of log2(FC) of miR29a targets as d) transcripts (RNA) and e) proteins (PROT) in transcriptomic and proteomic datasets of adult animals treated with amiR-29a. Notches correspond to confidence intervals of the median. Whiskers indicate 95th and 5th percentile, the box marks the 25th and 75th percentile. Significance vs. all detected genes and proteins, respectively, assessed by Wilcoxon's test (p-values shown in figure). ",
    "ncbi_link": "miR-29a: 387222
miR29a: 387222"
  },
  {
    "caption": "f) Box plots reporting distribution of log2(FC) of age down-regulated miR29a targets after amiR-29a treatment (N=4 scr treated and N=3 amiR-29a treated biological replicates). Notches correspond to confidence intervals of the median. Whiskers indicate 95th and 5th percentile, the box marks the 25th and 75th percentile. Significance was assessed with Wilcoxon's test (p-values shown in figure).",
    "ncbi_link": "miR-29a: 387222
miR29a: 387222"
  },
  {
    "caption": "h) Scatter plot correlating the expression changes of genes significantly regulated by age (log2FC, x-axis) and miR-29a antagonization by amiR29a in adult mice (log2FC, y-axis). (Spearman r=-0.22 p=1.4x10-8; Fisher test showing significant enrichment in the IV quadrant p=2.2x10-16). The number of genes for each quadrant is reported in figure.",
    "ncbi_link": "miR-29a: 387222
miR29a: 387222"
  },
  {
    "caption": "i) Scatter plot correlating the expression changes induced by miR-29a antagonization in adult mice at the transcript- (log2FC, x-axis) and protein-level (log2FC, y-axis). Spearman coefficient correlation, r=0.11; p=0.006, Fisher test showing significant enrichment in the I quadrant p=0.03. The number of genes for each quadrant is reported in figure.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "a) VEP analysis. Ratio between contralateral and ipsilateral eye responses (C/I ratio ± SEM) in animals treated with saline and not deprived (sal no MD), with scrambled LNA and MD (scr MD), with amiR-29a LNA and MD (amiR-29a MD). N=6/7; one-way ANOVA, p=0.0003; post hoc Tukey's test: sal noMD vs scr+MD, ns; sal noMD vs amiR-29a+MD, p=0.0002; scr+MD vs amiR-29a+MD, p=0.0169.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "b) IOS analysis. ODI ± SEM of deprived animals treated with scr (N=5, black lines) and amiR-29a LNA (N=6, blue lines). Dashed lines connect pre- and post-MD ODI values of each animal. Solid lines represent the group average. Two-way ANOVA RM, treatment X time, p= 0.0074; post hoc Sidak's test, pre-MD scr vs post-MD scr, ns; pre-MD vs post-MD amiR-29a, p=0.0005.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "c) IOS amplitude (± SEM) in response to contralateral eye (contra) and ipsilateral eye (ipsi) stimulation. Other conventions as in b). amiR-29a (N=6) vs scr (N=5). Contra eye: two-way ANOVA RM, time X treatment interaction p=0.034; post hoc Sidak's test; pre-MD vs post-MD scr, ns; pre-MD vs post-MD amiR-29a, p=0.0008. Ipsi eye: two-way ANOVA RM, time X treatment interaction, ns.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "d) Average time course of the IOS response to visual stimulation of the contralateral eye (contra) pre- and post-MD (thick black line). Grey area delimited by thin black lines envelops traces from scr animals (95% confidence interval); blue area envelop traces from amiR-29a animals (95% confidence interval). e) Same as in d) for ipsilateral eye (ipsi) pre- and post-MD responses. ",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "f) The effects of MD on Npas IV and Bdnf exIV expression is reported as the ratio between expression levels of deprived and nondeprived cortex for animals treated with scrambled (scr+MD) and amiR-29a (amiR-29a+MD). Each symbol represent the result of one animal. Error bars represent ±SEM. scr vs amiR-29a; t-test; N=7-9, Npas4: p=0.035; N=4-5; Bdnf exIV: p=0.026.",
    "ncbi_link": "Bdnf: 12064
miR-29a: 387222
Npas IV: 225872
Npas4: 225872"
  },
  {
    "caption": "g) Scatter plot correlating the changes in protein abundance induced by MD in young mice (MD CP, x-axis) with the effects observed in the adult deprived mice treated with amiR-29a (MD+LNA_AD, y-axis). Proteins present in both data sets and showing an absolute expression fold change (FC>0.1) are represented. Green symbols correspond to proteins with concordant direction of regulation; red symbols correspond to discordant regulation. Pearson correlation: r=0.19, p=0.019. The number of genes in each quadrant is reported in figure.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "a) Images of WFA-labeled PNNs of scrambled treated visual cortex (left) and miR-29a mimic (right) in young mice. Scale bar 60 µm. (b,c) Quantification of PNN density (scr vs mim29a, N=3 mice per group; t-test, p=0.20) and intensity for each animal (scr vs mim29a, N=3 mice per group; t-test, p=0.014). d) Cumulative frequency of PNNs staining intensity in scrambled and mimic treated young mice scr (N=1438 cells vs mim29a N=1749 cells, Kolmogorov-Smirnov test, p<0.0001). e) PNN distribution in classes of intensity in mice treated with scrambled and mimic 29a. ",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "f) Images of WFA-labeled PNNs of scrambled treated visual cortex (left) and amiR-29a LNA (right) in adult mice. Scale bar 60 µm. (g,h) Quantification of PNN density (scr vs amiR-29a, N=3 mice per group; t-test, p=0.03) and intensity for each animal scr vs amiR-29a, N=3 mice per group; t-test, p=0.047. i) Cumulative frequency of PNNs intensity in scrambled and amiR-29a treated adult mice. scr N=1883 cells vs amiR-29a N=1937 cells, Kolmogorov-Smirnov test, p< 0.0001. j) PNN distribution in classes of intensity in mice treated with scrambled and amiR-29a. ",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "k) Biochemical quantification of C4S in adult amiR-29a treated mice (N=5) as compared to scrambled animals (N=4). t test, p=0.0008.",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "l) Example of Arylsulfatase B (ArsB) western blot. Left: The lanes corresponding to the treated (treat scr or treat amiR-29a) and untreated (untreat scr or untreat amiR-29a) cortex (ctx) of two amiR-29a treated and two scr treated mice are reported. Right: quantification of the data shows ArsB upregulation by amiR-29a. The results are expressed as fold change normalized to untreated cortex. Each symbol represents the result of one animal. N=4, scr vs amiR-29a treated cortex, unpaired t test, p=0.043",
    "ncbi_link": "miR-29a: 387222"
  },
  {
    "caption": "MTT assay of vector control or INSL5 overexpressing CNE1, CNE2 and HK1 NPC cell lines (upper panel) either transfected with control siRNA (NC) or GPCR142 siRNA (#1 and #2) (lower panel). n=4 biological replicates for CNE1 and CNE2 cell line, n=6 biological replicates for HK1.",
    "ncbi_link": "INSL5: 10022
GPCR142: 339403"
  },
  {
    "caption": "colony formation (C and D) of vector control or INSL5 overexpressing CNE1, CNE2 and HK1 NPC cell lines either transfected with control siRNA (NC) or GPCR142 siRNA (#1 and #2). Representative images are shown in (C) for colony formation Number of colonies per field of view were plotted in D The results are from three different experiments.",
    "ncbi_link": "INSL5: 10022
GPCR142: 339403"
  },
  {
    "caption": "Brdu incorporation (E and F) of vector control or INSL5 overexpressing CNE1, CNE2 and HK1 NPC cell lines either transfected with control siRNA (NC) or GPCR142 siRNA (#1 and #2). Representative images are shown in (E) Brdu incorporation the percentage of Brdu positive cells were plotted in The results are from three different experiments. Scale bars represent 20μm in (E)",
    "ncbi_link": "INSL5: 10022
GPCR142: 339403"
  },
  {
    "caption": "migration assays (G and H) of vector control or INSL5 overexpressing CNE1, CNE2 and HK1 NPC cell lines either transfected with control siRNA (NC) or GPCR142 siRNA (#1 and #2). Representative images are shown in (G) for migration assays migrated cells per field of view were plotted in H, respectively. The results are from three different experiments. Scale bars represent 100μm in (G)",
    "ncbi_link": "INSL5: 10022
GPCR142: 339403"
  },
  {
    "caption": "I, J, Xenograft tumor growth of INSL5 over expression NPC HK1 stable cell lines in nude mice.. Tumor size (I) n=11 mice per group.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "Xenograft tumor growth of INSL5 over expression NPC HK1 stable cell lines in nude mice.. Tumor weight of two groups. n=11 mice per group.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "A, Gene expression profiles from CNE2 cells overexpressed with INSL5 or the vector control. The genes are shaded with green, black or red in the heat map to indicate low, intermediate or high expression, respectively.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "D, Analysis of glycolytic gene expression by immunoblot in INSL5 overexpressed or knock-down cell lines.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "E, Metabolites were purified from five (CNE1 cell line and HK1 cell line) or seven (CNE2 cell line) independent samples of two vector and INSL5 overexpressed cell lines and analyzed by liquid chromatography-mass spectrometry (LC-MS). Red: glycolytic intermediate metabolites. Green: tricarboxylic acid cycle (TCA cycle) intermediate metabolites. PPP: pentose phosphate pathway. The color scale bar represents Z-score of the metabolites' level.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "F, The extracellular acidification rate (ECAR) was measured in cells with or without INSL5 overexpression using a Seahorse XF96 Extracellular Flux analyzer. Glu, glucose; Oligo, oligomycin.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "G, Statistical analysis of the effects of INSL5 overexpression on glycolytic activity.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "H, CNE1-vector and CNE1-INSL5 cells were grown in the presence of the fluorescent glucose analog 2-NBDG (Invitrogen) for 15min, and glucose uptake was then quantified using flow cytometry (FACS) (left panel). Statistical analysis of the glucose uptake was showed in the right panel.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "glucose consumption and lactate production (I) in CNE1-vector and CNE1-INSL5 cells.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "basic ATP level or the ATP level of cell which was treated by 1uM oligomycin or 50uM 2-DG for 24h (J) in CNE1-vector and CNE1-INSL5 cells.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "HK2 enzyme activity (K) in CNE1-vector and CNE1-INSL5 cells.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "L, ATP concentration, HK2 enzyme activity and lactate production in INSL5 wide-type or knock down HNE1-EBV cells.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "C, Localization of STAT5. A confocal analysis of STAT5 staining was performed using CNE1 cells transfected vector or INSL5. Scale bars represent 20μm",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "D, Cytoplasmic and nuclear proteins from vector or INSL5overexpressing cells were separated and subjected to immunoblot as indicated. The nuclear marker Lamin B1 and the cytoplasmic marker GAPDH were used to demonstrate the purity of fractions.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "E, INSL5 overexpression activated AKT, ERK, JAK1 and STAT5 phosphorylation, not STAT3 in HK1 cells. INSL5 overexpressing HK1 cells were treated with MK2206 (50uM), U0126(20uM), MK2206+U0126, or Ruxolitinib (5uM) for 24h. Western blotting was performed to evaluate the effects of those inhibitors on STAT5 and STAT3 phosphorylation level.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "F, ChIP-qPCR analyzed the occupancy of potential E-boxes by STAT5 in the genes of HK2, Glut3 and PFK1 in INSL5-overexpressing CNE1 cells using IgG or anti-STAT5 antibodies.",
    "ncbi_link": "HK2: 3099
INSL5: 10022
PFK1: 5213
Glut3: 6515"
  },
  {
    "caption": "G, Luciferase activity of different glycolytic gene promoter reporters in 293T cells transfected with STAT5 or empty vector.",
    "ncbi_link": "STAT5: 6777///6776"
  },
  {
    "caption": "H, Glucose uptake assessed by 2-NBDG incubation in INSL5 overexpressed CNE1 cells with STAT5 knock down.",
    "ncbi_link": "INSL5: 10022
STAT5: 6777///6776"
  },
  {
    "caption": "I, Glucose uptake was assessed by 2-BNDG incubation in INSL5 overexpressed HK1 cells treated with JAK kinase inhibitor (Ruxolitinib).",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "J, MTT assay of vector control or INSL5 overexpressing HK1 cells either treated with STAT5 siRNAs or JAK kinase inhibitor.",
    "ncbi_link": "INSL5: 10022
STAT5: 6777///6776"
  },
  {
    "caption": "C-E Growth curves of cell lines stably expressing INSL5 or vector 48 h post-treatment with the indicated dose of glycolysis inhibitor, 2-DG. CNE1 cells (C), CNE2 cells (D) and HK1 cells (E). n=4 biological replicates for CNE1 and CNE2 cell line, n=6 biological replicates for HK1",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "F, Growth curves of cell lines stably expressing INSL5 or vector 48 h post-treatment with the indicated dose of cis-platinum (DDP) and 2-DG. n=4 biological replicates per group.",
    "ncbi_link": "INSL5: 10022"
  },
  {
    "caption": "(A) Representative images of immunofluorescence analysis (with anti-PlxnB2 antibodies) of the phenotype of COS7 cells transfected with wild-type or mutated PlxnB2, compared to the collapsed phenotype induced by the cognate ligand Sema4C (1 μg/ml) in cells expressing the WT receptor. (B) The stacked bar graph shows the fraction of collapsed PlxnB2-expressing cells, identified as having a surface minor of 2000 μm2 (measured by ImageJ software), out of 50-100 cells counted per each condition, from different fields and n>3 experiments). The statistical analysis was performed comparing WT untreated cells with all other groups, by Fisher's Exact Test, which indicated a *****p value < 0.00001 for Sema4C-treated and for G842C-PlxnB2-expressing cells (confirmed by ANOVA analysis on individual cell values, shown in Appendix Fig. S2). By Fisher's test, the only other mutants significantly different from WT were R820H (p< 0.001) and R843Q (p<0.01), although ANOVA analysis on individual cell values shown in Appendix Fig. S2 didn't confirm such significance for other PlxnB2 variants.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(A) The graphs show the analysis of cellular viability in shPlxnB2-tranduced agnospheres, compared to their respective scramble-transfected controls, after 24, 48, 72, and 96 hours of growth in culture. Values are mean ± SD of n≥3 independent experiments (6 technical replicates for each). The statistical significance was assessed by two-way ANOVA with Sidak's correction for multiple comparisons (Graph Pad Prism 8.0.0): **p = 0.0053; ****p < 0.0001.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(C) After transplantation in immunodeficient mice of CUP cells described above, the volume of ADX43- and (D) ADX901-shPlxnB2 tumors was assessed, in comparison with the respective controls. Plotted values indicate the mean ± SD (n = 8 each group). The statistical significance was assessed by two-way ANOVA with Sidak's correction for multiple comparisons: **p = 0.0060; ****p < 0.0001.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(A) Time course analysis of the cellular viability of AS901, stably overexpressing either wild-type or G842C-mutated PlxnB2, or controls transduced with an empty vector. Plotted values are the mean ± SD of n =3 independent experiments (six technical replicates for each). The statistical significance was assessed by two-way ANOVA with Tukey's correction for multiple comparisons. PlxnB2-G842C vs. controls (CTRL): at 24h **p = 0.0097, 48h **p = 0.0026, 72h **p = 0.0079, 96h *p = 0.0226. PlxnB2-G842C vs. PlxnB2-WT: at 48h $p = 0.0418, 72h $p = 0.0318. (B) Tumor growth curves of ADX 901 over-expressing either PlxnB2-G842C or PlxnB2-WT, or mock control. Plotted values are the mean ± SD (n = 8 each groups). The statistical significance was assessed by two-way ANOVA with Tukey's correction for multiple comparisons. PlxnB2-G842C vs control (CTRL): at 25 days **p = 0.0029, 28 days **p = 0.0028, 32 days **p = 0.0033. PlxnB2-G842C vs PlxnB2-WT: at 25 days $p = 0.0221, 28 days $p = 0.0234, 32 days $$p = 0.0024.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(A) Western blotting showing basal endogenous or overexpressed PlxnB2, either WT or G842C-mutated isoforms, in MCF7 cells. In this wide view of the hybridized membrane, it is appreciable the presence of full length molecules at 250 kDa, as well as the processed 80 kDa fragments (reported in ref. 64). Vinculin staining provided protein loading controls.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(B) The graph shows the mean ± SD of relative increase in 24-hour spontaneous migration across Transwell inserts of MCF7 cells (analysed above) over-expressing either wild-type or G842C-mutated PlxnB2, versus mock-transfected controls (n=4 biological replicates). The statistical significance was verified by one-way ANOVA with Bonferroni correction for multiple comparisons: PlxnB2-WT vs. mock *p=0.0145; PlxnB2-G842C vs. PlxnB2-WT *p=0.0277; PlxnB2-G842C vs. mock ***p=0.0002.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(D) Western blotting analysis of endogenous and overexpressed PlxnB2 (either WT or G842C-mutated isoforms) in CUP cells AS906 (both full length molecules at 250 kDa and processed 80 kDa fragments). Vinculin staining provided protein loading controls.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(E) The invasive capacity of CUP cells AS906 (shown in previous panel), overexpressing WT or G842-mutated PlxnB2 (or mock control), was assessed across Matrigel-coated transwell inserts. The graph shows the mean ± SD of values obtained in N=3 independent experiments (including technical duplicates, in two cases). Below the graph, are shown representative fields of the semipermeable membranes (additional larger size images can be found in appendix Figure S4C); scale bar: 100μm. The statistical significance was verified by one-way ANOVA with Bonferroni correction for multiple comparisons: *p=0.0406; **p=0.0045; ***p=0.0003.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(A) Phospho-EGFR analysis by western blotting in control and PlxnB2-silenced AS43 cells. Images show representative results of n=3 independent experiments, while the graph at the bottom shows the mean ± SD of normalized band quantification. The statistical significance across replicates was verified by unpaired t-test: ****p<0.0001. (B) Phospho-EGFR analysis by western blotting in AS901 and AS906 cells either mock, or overexpressing WT or G842C-mutated PlxnB2. Images show representative results of n=3 independent experiments, while the graphs at the bottom show the mean ± SD of normalized band quantification. The statistical significance across independent replicas was verified by one-way ANOVA followed by Tukey test: AS901 PlxnB2-G842C vs. PlxnB2-WT *p=0.0434, PlxnB2-G842C vs. mock *p=0.0211; AS906 PlxnB2-G842C vs. PlxnB2-WT *p=0.0436, PlxnB2-G842C vs. mock *p=0.0481.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(D) The invasive capacity of AS906 cells (overexpressing WT or G842C-mutated PlxnB2, or mock transfected) was assessed as in Fig. 7E, in the presence or absence of cetuximab 50μg/ml. Images show representative results (scale bar: 100μm), while the graph on the right shows the mean ± SD of n=3 independent experiments. The statistical significance across replicates was verified by one-way ANOVA with Bonferroni correction: **p= 0.0010; ***p=0.0005; ****p<0.0001.",
    "ncbi_link": "PlxnB2: 23654"
  },
  {
    "caption": "(C-F) show stage 10 egg chambers stained with anti-Vasa (C-F) or anti-GFP (E', F'). (C) wild type; (D) germline clones homozygous for the null allele btz2; (E) btz2 germline clones rescued with Btz-WT; (F) btz2 germline clones rescued with Btz-HD. Posterior is to the right. Scale bars, 80 μm. Vasa localization to the posterior pole of the oocyte is lost in btz mutants and is rescued by the wild type but not the EJC interaction-defective transgene. Wild-type Btz-GFP, but not the mutant form, is also slightly enriched at the posterior pole.",
    "ncbi_link": "btz: 43331
Btz: 43331"
  },
  {
    "caption": "(L-N) electron micrographs showing cross-sections of larval muscle 6 in segment A3, with the dorsal surface to the right. Scale bars, 10 μm. (L) btz2/+; (M) Df(3R)BSC497/+; (N) btz2/ Df(3R)BSC497. Yellow arrows indicate examples of mitochondria interspersed between muscle fibers, and red arrows indicate mitochondria at the dorsal surface. Scale bars, 2 μm.",
    "ncbi_link": "btz: 43331
Df: 248315"
  },
  {
    "caption": "(O) quantification of the ratio of the dorsal surface peak of ATP5 intensity to the second highest peak for the genotypes indicated. ***, p<0.001; **p<0.01; *p<0.05; ns, not significant by Mann-Whitney test. n=9 (btz/+), n=11 (Df/+, btz/Df), n=6 (btz/Df; G14>btz, C57-GAL4/+), n=4 (btz/Df; Btz-WT, C57>eIF4AIII RNAi), n=5 (btz/Df; Btz-HD), n=10 (C57>btz RNAi), or n=3 (C57>mago RNAi). Error bars show mean ± SEM.",
    "ncbi_link": "HD: 
btz: 43331
Btz: 43331
eIF4AIII: 40987
Df: 248315
GAL4: 855828"
  },
  {
    "caption": "(A-J) confocal images of the NMJ on larval muscles 6 and 7 in segment A3, stained with anti-HRP (magenta) to label the nerve and anti-Dlg (green) as a postsynaptic marker of synaptic boutons. (A) w1118 control; (B) btz2/+; (C) btz2/Df(3R)BSC497; (D) UAS-btz/+; da-GAL4, btz2/Df(3R)BSC497; (E) BG380-GAL4/+; UAS-btz/+; btz2/Df(3R)BSC497; (F) 24B-GAL4/UAS-btz; btz2/Df(3R)BSC497; (G) BG380-GAL4/+; 24B-GAL4/UAS-btz; btz2/Df(3R)BSC497; (H) BG380-GAL4/+; UAS-btz RNAi/+; (I) mhc-GAL4/UAS-btz RNAi; (J) repo-GAL4/UAS-btz RNAi. Scale bar, 30 μm. Insets in (A, C) show enlargements of the boxed regions, illustrating the closer spacing of boutons in btz mutants.",
    "ncbi_link": "btz: 43331
da: 34413
Df: 248315
GAL4: 855828
mhc: 35007
repo: 47285"
  },
  {
    "caption": "(K, L) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ***, p<0.001; **, p<0.01; ns, not significant by unpaired t-test with Welch's correction. n=23 (w; da-GAL4, btz/Df), n=6 (btz/+), n=10 (Df/+, UAS-BtzGFP/+; btz/Df), n=8 (btz/Df), n=22 (da>btz-GFP; btz/Df), n=13 (BG380-GAL4; btz/Df; BG380+24B>Btz-GFP; btz/Df; da-GAL4/+), n=5 (BG380>Btz-GFP; btz/Df), n=11 (24B-GAL4; btz/Df; da>btz RNAi), n=12 (24B>Btz-GFP; btz/Df; btz RNAi/+), n=9 (BG380+24B-GAL4; btz/Df), n=15 (BG380-GAL4/+), n=14 (BG380>btz RNAi; repo>btz RNAi), n=16 (mhc-GAL4/+), n=28 (mhc>btz RNAi), or n=21 (repo-GAL4/+). Error bars show mean ± SEM. NMJ size is reduced in btz mutants and rescued by expressing UAS-btz with da-GAL4 or with the combination of the BG380-GAL4 and 24B-GAL4 drivers, but not with any single driver. Expressing UAS-btz RNAi with da-GAL4 or in motor neurons with BG380-GAL4, muscles with mhc-GAL4 or glia with repo-GAL4 also reduces NMJ size.",
    "ncbi_link": "GFP: 
btz: 43331
Btz: 43331
da: 34413
Df: 248315
GAL4: 855828
mhc: 35007
repo: 47285"
  },
  {
    "caption": "(I) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ***, p<0.001 by unpaired t-test or Mann-Whitney test. n=15 (BG380-GAL4), n=12 (BG380>btz RNAi; BG380>mago RNAi; BG380>eIF4AIII RNAi), n=16 (btz/+), n=13 (btz/Df), or n=10 (Btz-WT; btz/Df; Btz-HD; btz/Df). Error bars show mean ± SEM. NMJ size is reduced by knocking down btz in motor neurons, but slightly increased by knocking down mago or eIF4AIII. The size deficit in btz mutants is equally well rescued by the wild type or EJC interaction-defective btz transgenes.",
    "ncbi_link": "HD: 
btz: 43331
Btz: 43331
eIF4AIII: 40987
Df: 248315
GAL4: 855828
mago: 37402"
  },
  {
    "caption": "(L) quantifications of the number of boutons normalized to muscle surface area (x1000) in the indicated genotypes. ****, p<0.0001; ns, not significant by unpaired t-test or Mann-Whitney test. n=19 (UAS-daw RNAi/+), n=9 (BG380>daw RNAi; btz/Df; tub>daw), n=23 (mhc>daw RNAi), n=10 (repo>daw RNAi; tub>daw), n=12 (btz/Df; UAS-daw), or n=14 (btz/Df; tub>btz). Error bars show mean ± SEM. Knocking down daw in motor neurons, muscles or glia reduces NMJ size. Expressing UAS-daw with tub-GAL4 rescues NMJ size in btz mutants as efficiently as expressing UAS-btz, but has no significant effect on NMJ size in a wild-type background.",
    "ncbi_link": "btz: 43331
daw: 33474
Df: 248315
GAL4: 855828
mhc: 35007
repo: 47285
tub: 40554"
  },
  {
    "caption": "mRNA expression  of Ifng, Tnfa, Il17f, and Il22. Colonic  transcription levels were normalized by Hprt, which was the most stable among the three housekeeping genes tested (Hprt, Hsp90, Gapdh). Longitudinal data of mean ± SEM is shown for 14SM FF, 14SM FR, and 13SM FR pups  at age   10-20 days (circles) with statistical significance calculated using two-way ANOVA factored on group and time point  compared to the 14SM FR  control. To the right of each longitudinal plot, we also report colonic  transcript levels for pups  born to germ-free (GF) FF  or FR   dams at age  15 days (squares) with statistical significance based on a one-way ANOVA with false-discovery adjustment using the Benjamini and Hochberg method. Outliers removed using ROUT method with Q = 10%. Data are from two independent experiments and represent biological replicates (n = 3-20/group).",
    "ncbi_link": "Gapdh: 14433
Hprt: 15452
Hsp90: 15516
Ifng: 15978
Il17f: 257630
Il22: 50929
Tnfa: 21926"
  },
  {
    "caption": "A) We identified previously unknown telomere regulators in fission yeast using the haploid S. pombe whole-genome gene deletion library including ssu72+ (SPAC3G9.04). B) Telomere length of wt, ssu72Δ and ssu72-C13S (point mutation at the phosphatase active site) strains were measured by Southern blot in ApaI digested genomic DNA using a telomeric probe. ",
    "ncbi_link": "ssu72: 2543452"
  },
  {
    "caption": "C) Ssu72 recruitment to telomeres is cell cycle regulated. Ssu72 was myc-tagged at the 3' end and ChIP analysis was carried out in cell cycle synchronized populations of cdc25ts strains. Septa formation was used proxy for S-phase. n ≥ 3; *p ≤0.05 based on a two-tailed Student's t-test to ssu72+ control samples. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "myc: 
cdc25: 2542632
Ssu72: 2543452
ssu72: 2543452"
  },
  {
    "caption": "D) Telomere length of ssu72Δ is dependent on telomerase. Diploid strains with the appropriate genotypes were sporulated and trt1∆ ssu72∆ double mutants were streaked for multiple passages (triangle indicates increased number of generations).",
    "ncbi_link": "ssu72: 2543452
trt1: 2540601"
  },
  {
    "caption": "E) Telomerase is recruited to telomeres in the absence of Ssu72. ChIP analysis for Trt1-myc in wt and ssu72∆ was performed as described in material and methods using a non-tagged strain as a control. n ≥ 3; *p ≤0.05 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "Ssu72: 2543452
ssu72: 2543452"
  },
  {
    "caption": "F) Telomerase activator Ccq1 is hyperphosphorylated in ssu72∆ cells. rap1∆ cells were used as positive control for Ccq1 phosphorylation status. Western blots were performed using Ccq1-flag tagged strains.",
    "ncbi_link": "flag: 
Ccq1: 2539352
rap1: 2540115
ssu72: 2543452"
  },
  {
    "caption": "A) ssu72Δ telomeres present longer G-rich overhangs than wt and rif1∆. In-gel hybridization in native and denaturing conditions was labelled with a radiolabelled C-rich telomere probe and quantified for ssDNA at the telomeres. n = 3; *p ≤0.05 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "rif1: 2542144
ssu72: 2543452"
  },
  {
    "caption": "B) RPA (Rad11-GFP) is enriched at ssu72∆ telomeres. Colocalization of Rad11-GFP with Taz1-mCherry, used as a telomere marker was performed in wt and ssu72∆ cells; n =3; *p ≤0.05 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM). More than 1000 cells were analyzed for each genotype",
    "ncbi_link": "ssu72: 2543452"
  },
  {
    "caption": "C) ssu72+ controls telomere length independently of rif1+. Epistasis analysis of telomere length of ssu72∆ and ssu72-C13S (catalytically inactive mutant) with rif1∆ was performed by Southern blotting of ApaI digested DNA using a telomeric probe. D) ssu72+ and stn1+ regulate telomere length in the same genetic pathway. Epistasis analysis of ssu72∆ and stn1-75 performed by Southern blotting of ApaI digested DNA using a telomeric probe. Two independently generated ssu72∆ stn1-75 double mutants are shown.",
    "ncbi_link": "rif1: 2542144
ssu72: 2543452
stn1: 2541052"
  },
  {
    "caption": "A) Ssu72 is required for telomere recruitment of Stn1 in late S phase. ChIP analysis of stn1-myc in wt and ssu72∆ cells was performed in synchronized cdc25ts cells. n ≥ 3; *p ≤0.05 based on a two-tailed Student's t-test to ssu72+ control samples. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "cdc25: 2542632
Ssu72: 2543452
ssu72: 2543452"
  },
  {
    "caption": "B) 2D-gel analysis of NsiI telomeric fragments of wt and ssu72∆ strains. Smart ladder from Eurogentec was used for DNA size measurement.",
    "ncbi_link": "ssu72: 2543452"
  },
  {
    "caption": "C) Serine 74 substitution to a phosphomimetic aspartate amino acid (stn1-S74D) is sufficient to confer ssu72∆ telomere defects. Telomere length epistasis analysis of ssu72∆ and stn1-S74D mutants were performed by Southern blotting of ApaI digested genomic DNA using a telomeric probe.",
    "ncbi_link": "ssu72: 2543452
stn1: 2541052"
  },
  {
    "caption": "E) Similar to ssu72∆ mutants, stn1-S74D is defective in telomere recruitment. ChIP analysis of stn1-myc and stn1-S74D-myc using a non-tagged strain as a control. n = 3; *p ≤0.05 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "ssu72: 2543452
stn1: 2541052"
  },
  {
    "caption": "A) ssu72+ and pol1+ regulate telomere length in the same genetic pathway. Epistasis analysis of ssu72∆ and pol1-13 mutants was performed by Southern blotting of ApaI digested DNA using a telomeric probe.",
    "ncbi_link": "pol1: 2543629
ssu72: 2543452"
  },
  {
    "caption": "B) Stn1-Pol1 interaction requires Ssu72 phosphatase. Immunoprecipitation experiments of Pol1-Flag with Stn1-Myc was preformed both in wt and ssu72∆ mutants. C) Immunoprecipitation of Ten1-Flag with Stn1-Myc in either wt or ssu72∆ was performed as control for Stn1-Ten1 complex integrity. ",
    "ncbi_link": "Flag: 
Myc: 
Pol1: 2543629
ssu72: 2543452
Ssu72 phosphatase: 2543452
Stn1: 2541052
Ten1: 9406926"
  },
  {
    "caption": "D) Overexpression of polymerase alpha partially rescues telomere length defect of ssu72Δ mutants. Multi-copy vector with polymerase α under thiamine promoter were expressed both in wt or ssu72Δ cells.",
    "ncbi_link": "polymerase alpha: 2543629
polymerase α: 2543629
ssu72: 2543452"
  },
  {
    "caption": "A) Telomere elongation of SSU72 down-regulated cells is telomerase dependent. Telomere Southern blot was carried out with HT1080 cells infected for 4 weeks with lentiviral particles carrying two independent shRNAs against SSU72 (CDS and UTR regions) and Luciferase (Luc) as control for shRNA. Knockdown efficiencies were determined by RT-qPCR using specific primers against hSSU72.",
    "ncbi_link": "Luciferase: 
hSSU72: 29101
SSU72: 29101"
  },
  {
    "caption": "B) Telomere elongation of SSU72 down-regulated cells is epistatic with STN1 downregulation. TRF analysis of HT1080 cells infected with the appropriate retroviral or lentiviral particles carrying either GFP shRNA, SSU72 shRNA (against UTR), STN1 shRNA or double SSU72 shRNA/STN1 shRNA. Cells were grown for 4 weeks and DNA was isolated to carry out Southern Blot analysis.",
    "ncbi_link": "GFP: 
SSU72: 29101
STN1: 79991"
  },
  {
    "caption": "C) hSSU72 down-regulation results in multi-telomeric signals (MTS) that are dependent on DNA replication. Visualization of mitotic spreads of HT1080 hSSU72 shRNA cells treated with aphidicolin and colcemid. Telomere FISH was carried out using a PNA-telomere probe. MTS are represented by arrows. Quantification of MTS per metaphase: n=4; **p ≤0.01 ****p ≤0.0001 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "hSSU72: 29101"
  },
  {
    "caption": "A) hSSU72 downregulation results in telomere DNA damage foci (TIF). Cells with indicated shRNAs were fixed and IF-FISH analysis was performed using a 53BP1 antibody and a PNA-telomere probe. (Right) Quantification of cells with more than 5 telomeric 53BP1 foci: n=3; **p ≤0.01 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "hSSU72: 29101"
  },
  {
    "caption": "B) hSSU72 is required for efficient loading of hSTN1 at human telomeres. ChIP was preformed using anti-FLAG antibodies and Southern blotting was performed using a human telomeric probe. Quantification of 3 independent ChIP experiments *p ≤0.05 **p ≤0.01 based on a two-tailed Student's t-test to control sample. Error bars represent standard error of the mean (SEM).",
    "ncbi_link": "hSSU72: 29101"
  },
  {
    "caption": "C Representative D-type motor neurons in wild-type and mxl-1 mutant animals 24 h after laser surgery. In wild-type animals, a severed axon has regenerated a growth cone (arrow). In mutants, proximal ends of axons failed to regenerate (arrowhead). Scale bar = 10 μm.",
    "ncbi_link": "mxl-1: 179557"
  },
  {
    "caption": "B Induction of Psvh-2::nls::venus expression in D-type motor neurons by laser surgery. Expression of fluorescent proteins in D-type motor neurons of wild-type, mxl-1, tdpt-1 and mxl-1; tdpt-1 animals 3 h after laser surgery are shown. Yellow arrowheads and white arrows indicate axon and cell bodies, respectively, of D-type neurons. White arrows indicate the sites of laser surgery. D neurons are visualized by CFP under control of the unc-25 promoter. Cell bodies of D-type neurons are magnified and shown within the red boxes. Most of the intestinal fluorescence in these photos is from endogenous and variable background autofluorescence. A schematic representation of D-type motor neurons is shown on the bottom. Scale bars = 10 μm.",
    "ncbi_link": "mxl-1: 179557
tdpt-1: 173276
unc-25: 176713"
  },
  {
    "caption": "B Interaction of MXL-1 with TDPT-1 by yeast two-hybrid assays. The reporter yeast strain L40u was co-transformed with expression vectors encoding LexA DBD-MXL-1 and GAL4 AD-TDPT-1 as indicated. Yeasts carrying the indicated plasmids were grown on a selective plate lacking histidine and containing 10 mM 5-aminotriazole for 4 days.",
    "ncbi_link": "GAL4: 855828
LexA: 20466968
MXL-1: 179557
TDPT-1: 173276"
  },
  {
    "caption": "B Interaction between ETS-4 and TDPT-1. COS-7 cells were transfected with plasmids encoding T7-TDPT-1, HA-ETS-4 (WT), HA-ETS-4(S73E) (SE) and HA-ETS-4(S73A) (SA), as indicated. Whole-cell extracts (WCE) and immunoprecipitated complexes obtained with anti-T7 antibody (IP: T7) were analyzed by immunoblotting (IB).",
    "ncbi_link": "HA: 
T7: 
ETS-4: 180927
TDPT-1: 173276"
  },
  {
    "caption": "C In vitro SUMOylation of ETS-4. COS-7 cells were transfected with plasmids encoding HA-ETS-4 (WT) and HA-ETS-4(K32A; K83A) (2KA), as indicated. Cell lysates were immunoprecipitated with anti-HA antibody. The immunoprecipitates were subjected to in vitro SUMOylation assays. Reaction mixtures were analyzed by immunoblotting (IB) with anti-SUMO-2/3 and anti-HA antibodies. Arrows mark the SUMOylated-ETS-4 bands.",
    "ncbi_link": "HA: 
ETS-4: 180927"
  },
  {
    "caption": "E SUMOylation of ETS-4 in mammalian cells. HEK293 cells were transfected with plasmids encoding HA-ETS-4 (WT), HA-ETS-4(K32A; K83A) (2KA), T7-TDPT-1, His-SUMO-1, His-SUMO-2 and Myc-MXL-1, as indicated. SUMO-conjugated proteins were isolated by cobalt affinity chromatography. ETS-4 was detected by immunoblotting with anti-HA antibody. Whole-cell extracts (WCE) were analyzed by immunoblotting (IB).",
    "ncbi_link": "HA: 
His: 
Myc: 
SUMO-1: 
SUMO-2: 
T7: 
ETS-4: 180927
MXL-1: 179557
TDPT-1: 173276"
  },
  {
    "caption": "A Effect of phosphorylation of ETS-4 on SUMOylation of ETS-4 in mammalian cells. HEK293 cells were transfected with plasmids encoding HA-ETS-4 (WT), HA-ETS-4(K32A; K83A) (2KA), HA-ETS-4(S73A) (SA), HA-ETS-4(S73E) (SE), T7-TDPT-1 and His-SUMO-2, as indicated. SUMO-conjugated proteins were isolated by cobalt affinity chromatography. ETS-4 was detected by immunoblotting with anti-HA antibody. Whole-cell extracts (WCE) were analyzed by immunoblotting (IB).",
    "ncbi_link": "HA: 
His: 
SUMO-2: 
T7: 
ETS-4: 180927
TDPT-1: 173276"
  },
  {
    "caption": "B Effect of SUMOylation of ETS-4 on PKA phosphorylation of ETS-4 in vitro. COS-7 cells were transfected with plasmids encoding HA-ETS-4 (WT), HA-ETS-4(S73A) (SA) and HA-ETS-4(K32A; K83A) (2KA), as indicated. Cell lysates were immunoprecipitated with anti-HA antibody. The immunoprecipitates were subjected to in vitro PKA kinase assays or in vitro SUMOylation and then in vitro PKA kinase assays, using recombinant GST-fused active PKA, as indicated. Reaction mixtures were analyzed by immunoblotting (IB) with anti-phospho-PKA substrate, anti-SUMO-2/3 and anti-HA antibodies. Arrows mark the SUMOylated-ETS-4 bands. Asterisk indicates the non-SUMOylated- and phosphorylated-ETS-4 bands.",
    "ncbi_link": "HA: 
ETS-4: 180927"
  },
  {
    "caption": "B Expression levels of RBM15 and AS-RBM15 in different blood lineages by meta-analysis of RNA-seq data [38]: HSC (hematopoietic stem cells), MPP (multipotent progenitor cells), CMP (common myeloid progenitor cells), CLP (common lymphoid progenitor cells), GMP (Granulocyte-macrophage progenitor cells), MEP (megakaryocyte- erythrocyte progenitor cells), MK (megakaryocyte), and EB (erythroid body).",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "C Relative expression levels of AS-RBM15 (left) and RBM15 (right) in MEG-01 cells treated with PMA were measured by real-time PCR assays (n=4, mean ± SD). SD: standard deviation.",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "D Relative expression levels of AS-RBM15 and RBM15 in CD34+ cells grown in pro-MK medium were measured by real-time PCR. GAPDH was used as an internal control (n=3, mean ± SD). Also see Fig EV 1.",
    "ncbi_link": "AS-RBM15: 
GAPDH: 
RBM15: 64783"
  },
  {
    "caption": "A CFU-MK assays with CD34+ cells expressing AS-RBM15. MK colonies staining for acetylcholinesterase activity were counted (right). P value was calculated using Student's t test (n=3, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "B The number of CD41+CD42+ mature MK cells was determined by FACS analysis. CD34+ cells expressing sh-AS-RBM15 were grown in pro-MK medium containing thrombopoietin and stem cell factor (TPO/SCF) for five days (n=4, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "D FACS analysis of CD34+ cells grown in pro-MK medium and expressing AS-RBM15 full length or Δ5 or Δ3. The CD41+CD42+ cell percentages were analyzed using one way ANOVA, ** P<0.01, (n=4, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "E The percentage of CD41+CD42+ cells in CD34+ cells expressing AS-RBM15 Exon 1 were determined by FACS analysis after these cells were grown in pro-MK medium for five days. P value was calculated by t test, p<0.01, (n=3, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "A RBM15 protein levels in leukemia cell lines (MEG-01, K562, HEL) were assessed by Western blotting (WB) (left) (n=3). The mRNA levels of RBM15 in cells overexpressing AS-RBM15 were measured by real-time PCR (right, n=3, mean ± SD). GAPDH was used as an internal control for WB and PCR.",
    "ncbi_link": "AS-RBM15: 
GAPDH: 
RBM15: 64783"
  },
  {
    "caption": "B Protein levels (left) and mRNA levels (right) of RBM15 in MEG-01 cells expressing two different shRNAs against AS-RBM15 respectively were measured using WBs and real-time PCR assays, respectively (n=3, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "C Protein levels (left) and mRNA levels (right) of RBM15 in MEG-01 cells expressing truncated AS-RBM15 RNAs (the schematic as shown on Fig 2C) were measured using WB and real-time PCR respectively (n=3, mean ± SD).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "D The role of AS-RBM15 in protein translation was assessed by reporter assays. The reporter under control of the CMV promoter contains the 5'UTR of RBM15 mRNA ligated to firefly luciferase followed by an IRES element controlling Renilla luciferase as an internal control. The reporter plasmid was cotransfected with plasmids expressing full-length, exon 1 and Δ5 AS-RBM15 respectively. The vector reporter without 5'UTR is a negative control. (n=3, mean ± SD). P values were calculated by one-way ANOVA test (*p<0.05, **p<0.01 and ***p<0.001).",
    "ncbi_link": "AS-RBM15: 
firefly: 
Renilla: 
RBM15: 64783"
  },
  {
    "caption": "A Cytoplasmic extracts from MEG-01 cell lines stably expressing AS-RBM15, Exon 1, or shRNA-02 against AS-RBM15 were fractionated through sucrose gradients (15%-60%) (n=4). Global polyribosome profiles of these cell lines were generated by UV absorbance at 254 nm (A254). The arrow indicates increasing polyribosome weights. Low molecular weight, LMW; high molecular weight, HMW.",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "B The distributions of RBM15 mRNA (top), GAPDH mRNA (middle), and AS-RBM15 (bottom) were measured by real-time PCR and represented as percentages of total RNA in the fractions (n=3).",
    "ncbi_link": "AS-RBM15: 
GAPDH: 2597
RBM15: 64783"
  },
  {
    "caption": "C MS2 pull-down assays: AS-RBM15 full-length (FL) and exon 1 were fused to MS2RNA as baits. Plasmids expressing MS2 binding protein ( HA-tagged) and fusion baits were co-transfected into 293T cells. HA antibody was used to immunoprecipitateHA-MS2 binding protein as shown by a WB on the bottom panel. RBM15 mRNA and MS2 fusions were assessed by real-time PCR (n=3, mean ± SD). Fold enrichment was calculated as 2 to the power of [(CI.R-Cb.R)-(CI.MS2-Cb.MS2)]. I: input i.e. the RNA in solution before immunoprecipitation, R: RBM15 mRNA, b: bead-bound mRNA, MS2: RNA levels of MS2 fusions, C: number of cycles in real-time PCR. One-way ANONA for p value: p<0.05.",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "D WB analysis of the endogenous RBM15 protein levels in 293T cells overexpressing two different doses of AS-RBM15-MS2 and MS2 (n=3).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "E RBM15 mRNA interacts with AS-RBM15 via RNA-RNA interaction. AS-RBM15-MS2-associated RNAs were purified by phenol extraction and measured by reverse transcription and PCR for detection of RBM15, AS-RBM15 and MS2 under denaturing (heat) and non-denaturing conditions (n =3).",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "F RNase A protection assays for detecting endogenous association of AS-RBM15 and RBM15 mRNA (n=4). RNA was extracted from MEG-01 cells with phenol and digested with RNase A. cDNA was synthesized after RNase A treatment and detected using AS-RBM15 exon-specific primers as shown in the schematic diagram on top. RT: reverse transcriptase.",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "G MEG-01 cells expressing AS-RBM15 or vector control were treated with DMSO or rapamycin for 45 minutes. Cells were harvested for WB using antibodies against GAPDH and RBM15 (n=2).",
    "ncbi_link": "AS-RBM15: "
  },
  {
    "caption": "H The RBM15 5'UTR reporter remains sensitive to rapamycin treatment with or without overexpression of antisense AS-RBM15 (n=4, mean ± SD). P values were calculated by one-way ANOVA test (**p<0.01 and ***p<0.001).",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783"
  },
  {
    "caption": "The subcellular distribution of RBM15 and AS-RBM15 in CD34+ cells grown in TPO-containing medium for 5 days. Cytoplasmic and nuclear RNA levels of AS-RBM15 and RBM15 were normalized to GAPDH (control for cytoplasmic fraction) and MALAT1 (control for nuclear fraction), respectively, using the ΔΔCt method (n=4, mean ± SD).",
    "ncbi_link": "AS-RBM15: 
GAPDH: 
MALAT1: 
RBM15: 64783"
  },
  {
    "caption": "A RUNX1 expression levels in human CD34+ cells grown in pro-MK medium in a time course were measured by real-time PCR (n=4, mean ± SD).",
    "ncbi_link": "RUNX1: 861"
  },
  {
    "caption": "C The mRNA expression levels of RUNX1, RBM15, and AS-RBM15 in RUNX1 knockdown MEG-01 cells were measured by real-time PCR (n=4, mean ± SD).",
    "ncbi_link": "AS-RBM15: 
RBM15: 64783
RUNX1: 861"
  },
  {
    "caption": "D Chromatin immunoprecipitation using anti-RUNX1 antibody. Immunoprecipitated DNA fragments were measured by real-time PCR using HEL cells expressing shRUNX1 and control (n=4, means ± SD).",
    "ncbi_link": "RUNX1: 861"
  },
  {
    "caption": "E CD34+ human cord blood cells were transduced with MIG retroviruses co-expressing A/E (AML1-ETO, aka RUNX1-ETO) and GFP. Around 5 days after transduction, the GFP+CD11b- cells were sorted for real-time PCR (n=4). Also see Fig EV6 for RUNX1-ETO binding profile on RBM15 locus.",
    "ncbi_link": "RBM15: 64783
AML1: 861
RUNX1: 861
ETO: 862"
  },
  {
    "caption": "(A) Volcano plot of phosphorylation changes in iKras PDAC cells in response to KrasG12D induction. Phospho- to total proteomic changes were quantified from three independent biological replicates of Dox treated vs. untreated cells, via TMT (Dataset EV8). 872 phosphorylations were found to be significantly increased, while 82 phosphorylations were significantly decreased (FDR < 0.05). Significantly changing phosphorylations on RBPs whose RNA-binding activity was significantly increased (red) or decreased (blue) as per Fig 1C are highlighted on the plot.",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "(E) KrasG12D induction enhances phosphorylation of CK2α (T360/S362), in an Erk1/2-dependent manner. IKras PDAC cells were grown in the absence of Dox for 48 hrs, before its addition to the indicated cells, with or without Trametinib (10 nM), for a further 24 hrs. Cells were then lysed and analyzed by immunoblotting (IB) with the indicated antibodies. The red triangle marks the main phospho band which overlaps with the total CK2α.",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "(G) Analysis of the RNA-binding activity of WT, Phospho-defective (S4A), and phospho-mimicking (S4D) mutants of Ncl by OOPS. IKras PDAC cells were transiently transfected with myc-tagged WT, S4A, and S4D Ncl constructs. Cells were subsequently grown in the absence of Dox for 48 hrs, followed by Dox addition for 24 hrs to induce KrasG12D expression. Cells were then subjected to OOPS to isolate the interface (RNA-bound proteins), or whole cell lysis (total lysate), followed by immunoblotting with anti-Ncl antibody. For comparison, Gapdh, which also binds RNA but does not show a change in its RNA-binding activity (Dataset EV1), was also blotted for. A fraction of each interface or total lysate sample was also subjected to RNA extraction, which was resolved and quantified by capillary electrophoresis (CE) as loading control.",
    "ncbi_link": "myc: 
Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(B) Immunofluorescence analysis of WT, S4A, and S4D Myc-Ncl subcellular localization. IKras PDAC cells ectopically expressing either WT, S4A, or S4D Myc-Ncl were fixed and immunostained with anti-Myc-tag antibody, along with anti-Fibrillarin (Fbl) antibody as a Nucleolar marker, and Hoechst, followed by confocal microscopy analysis.",
    "ncbi_link": "Myc: 
Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(C) Distribution of WT, S4A, and S4D Myc-Ncl crosslink sites across the annotated 47S pre-rRNA genomic region. Peak heights represent mean crosslink intensities from three independent iCLIP replicate experiments.",
    "ncbi_link": "Myc: 
Ncl: 17975"
  },
  {
    "caption": "(D) Quantification of the percentage of crosslinks in each region of the 47S pre-rRNA for WT, S4A, and S4D Myc-Ncl. Percentage of crosslinks relative to 47S total were quantified from three independent biological replicate iCLIP experiments. (E) Quantification of the proportional density of crosslinks in each region of the 47S pre-rRNA for WT, S4A, and S4D Myc-Ncl. Proportional density was calculated from three independent iCLIP experiments by normalizing the number of crosslinks in each region to the sequence length of that region.",
    "ncbi_link": "Myc: 
Ncl: 17975"
  },
  {
    "caption": "(A) Nascent RNA imaging in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, grown for 48hrs in presence or absence of Dox, prior to pulse labeling with FUrd. Cells were then fixed and immunostained with anti-FUrd antibody (green) to visualize nascent RNA, along with anti-Fibrillarin (Fbl) antibody as a Nucleolar marker (red), and Hoechst (blue) as the Nuclear stain, followed by confocal microscopy analysis. (B) Quantification of Nucleolar FUrd levels in images from (A). FUrd fluorescence densities in single nucleoli were quantified from 182-220 individual cells per condition, combined from 2 independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "ncbi_link": "Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(C) RT-qPCR analysis of 5'ETS-containing pre-rRNA transcript levels in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, and grown for 48hrs in presence or absence of Dox, before RT-qPCR analysis with a specific probe against the mouse 5'ETS region. A probe against mouse Actb mRNA was used as loading control for normalization. A total of 4 biological replicate experiments were quantified (***: P < 0.001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "ncbi_link": "Actb: 11461
Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(E) Assessment of the overall protein synthesis rates in control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D, by puromycinylation. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, and grown for 48hrs in presence or absence of Dox, before pulse labelling with Puromycin (10 μg/ml) for 15 min to label nascent proteins. Cells were subsequently lysed and analyzed by immunoblotting with the indicated antibodies. (F) Quantification of puromycin incorporation from (E), as an indicator of the overall protein synthesis rate. Total Erk1/2 levels were used as loading control. A total of 4 independent biological replicate experiments were quantified. Error bars depict SD. (**: P < 0.01; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test). (",
    "ncbi_link": "Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(G) Nascent RNA imaging of WT, S4A, and S4D Myc-Ncl expressing iKras PDAC cells, in presence or absence of KrasG12D. Vectors encoding Myc-tagged WT, S4A, and S4D Ncl were transiently transfected into iKras PDAC cells, before reseeding and growing the cells for 48hrs in presence or absence of Dox. Cells were then subjected to pulse labeling with FUrd, fixation, and immunostaining with anti-FUrd antibody (green), anti-Myc-tag antibody (red), and Hoechst (blue), followed by confocal microscopy analysis. Scale bar = 10 µm. (H) Quantification of FUrd levels in Myc-positive nucleoli from (E). FUrd fluorescence densities in single nucleoli were quantified from 160-281 individual cells per condition, combined from three independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test). (",
    "ncbi_link": "Myc: 
Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(I) RT-qPCR analysis of 5'ETS-containing pre-rRNA transcript levels in WT, S4A, and S4D Myc-Ncl expressing iKras PDAC cells, in presence or absence of KrasG12D. Vectors encoding Myc-tagged WT, S4A, and S4D Ncl were transiently transfected into iKras PDAC cells, before reseeding and growing the cells for 48hrs in presence or absence of Dox, followed by RT-qPCR analysis with a specific probe against the mouse 5'ETS region. A probe against mouse Actb mRNA was used as loading control for normalization. A total of 5 to 8 biological replicate experiments per condition were quantified (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "ncbi_link": "Myc: 
Actb: 11461
Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(A) Colony formation of control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, followed by clonogenic assay for 7 days in presence or absence of Dox. Colonies were visualized by Crystal Violet staining. (B) Quantification of Crystal Violet staining levels from (A). A total of 6 biological replicate experiments were quantified. Error bars depict SD. (****: P < 0.0001; n.s.: not significant - calculated from two way ANOVA with Šídák's multiple comparisons test). (",
    "ncbi_link": "Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(C) 3D proliferation of control and Ncl depleted iKras PDAC cells, in presence or absence of KrasG12D. Cells were transfected with a non-targeting control siRNA, or two independent siRNAs against Ncl, before being reseeded onto 3D Collagen-I gels, with or without Dox, and allowed to grow for 48 hrs. Cells were subsequently imaged live by phase contrast microscopy. Scale bar = 200 µm. (D) Analysis of the relative percentage of viable cells in 3D collagen-I cultures from (C). Cells were subjected to luminescence-based viability assay by CellTiter-Glo to quantify the percentage of viable cells. A total of 3 biological replicate experiments were quantified. Error bars depict SD. (****: P < 0.0001; n.s.: not significant - calculated from two way ANOVA with Šídák's multiple comparisons test). (",
    "ncbi_link": "Kras: 16653
Ncl: 17975"
  },
  {
    "caption": "(A) Dose response analysis of CX-5461 impact on nascent rRNA expression. IKras PDAC cells were grown in the absence of Dox for 48hrs. Cells were subsequently treated with or without Dox for 24 hrs to induce KrasG12D expression, followed by pre-treatment with the indicated concentrations of CX-5461 for 30 mins prior to pulse labeling with FUrd. Cells were then fixed and immunostained with anti-FUrd antibody to visualize nascent RNA (green), anti-Ncl antibody to reveal the Nucleolus (red), and Hoechst (blue) as the Nuclear stain, followed by confocal microscopy analysis. (B) Quantification of Nucleolar FUrd levels in images from (A). FUrd fluorescence densities in single nucleoli were quantified from 251-479 individual cells per condition, combined from 2 independent biological replicate experiments (****: P < 0.0001; n.s.: not significant - calculated from one-way ANOVA with Šídák's multiple comparisons test).",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "(G) MRI imaging of orthotopic iKras tumors in untreated or CX-5461 treated mice. IKras PDAC cells were engrafted into the pancreas of Dox-fed nude mice and allowed to form tumors for 4 days. Animals were then divided into two groups, with the first group treated by daily oral administration of CX-5461 (50mg/kg) for a further 10 days, whilst the second group was left untreated for the same period. T2 scans were taken on the indicated days, post-engraftment. Green areas mark the tumors.",
    "ncbi_link": "Kras: 16653"
  },
  {
    "caption": "(c) Absolute quantitative PCR of TCF20 in different developmental stages from E12 to P0. n=4 independently repeated tests.",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(f) In utero electroporation of TCF20 shRNAs in the E13 cerebral cortex led to abnormal cell distribution. These electroporated embryos were collected at E16. (g) Statistical analysis of the distributions of GFP-positive cells in different brain regions. The percentage of GFP-positive cells in the CP (cortical plate), IZ (intermediate zone), and VZ/SVZ (ventricle zone and subventricle zone) was analyzed. n=7 brains. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.01(**), p<0.001(***). Scale bar in (F) 50 μm.",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(d) Western blotting analysis indicated an increase in the proliferation marker Sox2 in TCF20 depleted NSCs.",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(a) SATB2 staining revealed a reduction in SATB2 and GFP colocalization when TCF20 was depleted. White arrows represent SATB2, GFP double-positive cells. (b) Statistical analysis of the SATB2 GFP double-positive cell ratio in GFP positive cells. n=3 brains. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***). Scale bar: 25 μm",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(c) Staining with CTIP2 and TBR1 antibodies shows TCF20 knockdown decreases the colocalization of CTIP2 and TBR1 with GFP in E13.5-E16.5 brains. White arrows represent CTIP2, GFP double-positive cells. White arrow heads represent TBR1, GFP double-positive cells. (d, e) Statistical analysis of CTIP2, GFP and TBR1, GFP double-positive cell ratio in GFP positive cells. n=3 brains. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***). Scale bar: (d) 50 μm",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(b) Western blotting analysis of TCF20 in TCF20 WT, HET, KO mice reveals that TCF20 was deleted. (c) Statistical analysis of the normalized band intensity of TCF20. n=3 samples for each genotype. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(d) RT-qPCR analysis of TCF20 in TCF20 WT, HET, and KO mice reveals that TCF20 was deleted. n=4 samples. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(e) Immunostaining of E16 WT and KO mouse brain slices revealed that TCF20 was successfully knocked out. Scale bar: 50 μm. (f) Statistical analysis of the normalized fluorescence intensity of TCF20. n=6 samples for each genotype. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(g) Western blotting analysis of neural proliferation and differentiation markers in WT HET and KO mice showed that TCF20 deficits promote cell proliferation and inhibit cell differentiation.",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(h) Immunostaining of different cortical layer markers TBR1, CTIP2, and SATB2, White dash line represents the positive area. Scale bar: 50 μm. (i-k) Statistical analysis of different cells layers in TCF20 WT, HET and KO mice. n=7 brains of each group. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(l) TCF20 deletion impairs neurogenesis and results in abnormal cell distribution. Scale bar: 50 μm. (m) Statistical analysis of GFP+ distribution in different zones. n=3 brains for each genotype. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**), p<0.001(***).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(d) TDG is significantly decreased after TCF20 deletion.",
    "ncbi_link": "TCF20: 21411
TDG: 21665"
  },
  {
    "caption": "(e) Volcano map showing that TDG is significantly decreased.",
    "ncbi_link": "TDG: 21665"
  },
  {
    "caption": "(f, g) Electroporation of GFP at E13.5 to E16.5 in TCF20 KO mice impairs cell distribution. n=3 brains. Scalebar 25 μm Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**).",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(h) Chip-qPCR of TCF20 binding to the TDG promoter. n= 4 biological repeats. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**).",
    "ncbi_link": "TCF20: 21411
TDG: 21665"
  },
  {
    "caption": "(b) TDG ChIP-qPCR revealed that TDG mainly binds to TCF-4 CpG islands. Seven regions (from -5 kbp to -200 bp) of the promoter were analyzed. -500 bp and -200 bp regions were located in the CpG island of the TCF-4 promoter. (n=4 biological repeats). Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**). and p<0.001(***). ",
    "ncbi_link": "TCF-4: 21416
TDG: 21665"
  },
  {
    "caption": "(c-f) MeDIP-qPCR showed that 5fC, 5caC, and 5mC are increased in the TCF-4 promoter, while 5hmC is decreased when TCF20 is insufficient. The MeDIP assay measure the region -500 bp from the TCF-4 promoter. (n=4 biological repeats) Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**). and p<0.001(***). ",
    "ncbi_link": "TCF20: 21411
TCF-4: 21416"
  },
  {
    "caption": "(g) NSCs were isolated from C57B6/J E13.5 embryonic brains and then were infected with a lentivirus containing a TCF20 shRNA or with a control plasmids. Immunostaining of 5fC shows that TCF20 depletion increased 5fC levels. White dashed lines show the cells infected with lentivirus. Scalebar 25 μm (h)Statistical analysis of 5fC fluorescence level. n=20 cells, and P<0.0001 Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**). and p<0.001(***). ",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(i) Immunostaining of 5caC shows that TCF20 depletion increased 5caC level. White dashed lines show the cells infected with lentivirus. Scalebar 25 μm. (j) Statistical analysis of the 5caC fluorescence level. n=20 cells, and P<0.0001. Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**). and p<0.001(***). ",
    "ncbi_link": "TCF20: 21411"
  },
  {
    "caption": "(k, l) Overexpression of TDG and TCF-4 rescued the TCF20 knockdown phenotype in brains; n=3 brains. Scalebar 50 μm Data information: Error bars represent the means ± S.E.M. Two tailed unpaired T-tests were used to analyze the data, n.s. (no significant difference), p<0.05(*), p<0.01(**). and p<0.001(***). ",
    "ncbi_link": "TCF20: 21411
TCF-4: 21416
TDG: 21665"
  },
  {
    "caption": "MEFs expressing vector, TRPML-1, or GRP1-DD were treated with BSA or palmitate (250 μM) for 3 h and stained as in (A). aspect ratio (O), branch length (P), and roundness (Q) of mitochondria in the cells in (N).",
    "ncbi_link": "GRP1: 19159
TRPML-1: 94178"
  },
  {
    "caption": "Chop, Xbp1s, Atf6, and Grp78 mRNA measured in eWAT resected from mice maintained on a HFD for 13 weeks and gavaged with vehicle or 120 mg/kg SH-BC-893 on Monday, Wednesday, and Friday for the final 3 weeks; n=7-9.",
    "ncbi_link": "Atf6: 226641
Chop: 13198
Grp78: 14828
Xbp1s: 22433"
  },
  {
    "caption": "Vector mediated eGFP expression after intravitreal injection of novel capsid variants compared to controls in 2-month-old mice. (A) In vivo cSLO examinations of the mouse retina at 1- and 2-weeks post injection (WPI) of 2E9 total vg (in 1 µl) of sc-CMV-eGFP packaged with parental serotype AAV2 , state-of-art AAV2.7m8, novel AAV2.GL and AAV2.NN capsid variants.",
    "ncbi_link": "CMV: "
  },
  {
    "caption": "(F) qRT-PCR data comparing fold change in eGFP transcript levels from retinal samples infected with capsid variants AAV2.7m8, AAV2.GL and AAV2.NN compared to AAV2.",
    "ncbi_link": "eGFP: "
  },
  {
    "caption": "(B) qRT-PCR data comparing fold change in eGFP transcript levels relative to ITR2 amplicons from retinal samples infected with all four capsid variants.",
    "ncbi_link": "eGFP: 
ITR2: "
  },
  {
    "caption": "Vector mediated eGFP expression after intravitreal injection in 10-month-old dog eyes. (A) In vivo cSLO examinations of the dog retina at four, five and six weeks post intravitreal injection of 2E11 total vg (in 200 µl) of sc-CMV-eGFP packaged with wildtype AAV2 (right eye), AAV2.GL (right eye) and AAV2.NN (left eye) capsid variants.",
    "ncbi_link": "CMV: "
  },
  {
    "caption": "Vector mediated expression after intravitreal injection in ~3-year old cynomolgus macaque eyes. (A-B) In vivo cSLO examination images collaged to provide NHP fundus overview at 8 WPI of E12 total vg (in 38.9-100 µl) of sc-CMV-eGFP packaged with AAV2.GL and AAV2.NN capsid variants, respectively. ",
    "ncbi_link": "CMV: "
  },
  {
    "caption": "Vector mediated eGFP expression in human retinal explants. (B) EVOS epifluorescence images at 2x magnification of the human retinal explants at three, six and nine days in vitro (DIV) after transduction with 1E11 total vg of sc-CMV-eGFP packaged with AAV2.GL and AAV2.NN capsid variants. White signal indicates eGFP.",
    "ncbi_link": "CMV: "
  },
  {
    "caption": "(G-I) Confocal images of Cnga3-/- treated (G), wildtype (H) and Cnga3-/- untreated (I) retinal sections stained for Cnga3. Note some non-specific signal detected in INL and adjacent synaptic layer. Scale bar: 50 μm. OS, outer segment layer; ONL, outer nuclear layer; INL, inner nuclear layer.",
    "ncbi_link": "Cnga3: 12790"
  },
  {
    "caption": "(A) Using denaturing immunoprecipitation (IP), Munc18-1 was isolated from cell lysate of HEK293T cells expressing M18WT, M18Y145F or M18Y473F together with or without n-Src. Munc18-1 was immunoblotted for tyrosine phosphorylation using the 4G10 antibody (αPtyr), after which the blot was stripped and re-blotted for Munc18-1. Total lysate (TL) is shown as loading control. N-Src was tagged with a flag-tag for visualization.",
    "ncbi_link": "Src: 6714
M18: 6812"
  },
  {
    "caption": "(B) Same as (A) but using lysate from HEK293T cells expressing M18WT or M18Y473F together with or without n-Src, c-Src or Fyn. The first two lanes are IPs performed using empty beads to control for non-specific binding of Munc18 or kinases to the beads.",
    "ncbi_link": "Fyn: 2534
Src: 6714
M18: 6812"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using confocal microscopy (A) Typical confocal images from neurons stained for MAP2, Synaptobrevin/VAMP2 and Munc18-1.",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using confocal microscopy (B) Average synaptic Munc18-1 intensity (M18WT: 389 ± 85 a.u., n=21; M18Y473D: 261 ± 49 a.u., n=20, t-test with Welch correction, p = 0.2000), somatic Munc18-1 intensity (M18WT: 328 ± 49 a.u., n=21; M18Y473D: 188 ± 21 a.u., n=20, t-test with Welch correction, p = 0.0138), synapse number (M18WT: 129 ± 14, n=21; M18Y473D: 159 ± 14, n=20, t-test, p = 0.1203) and dendrite length (M18WT: 0.433 ± 0.028, n=21; M18Y473D: 0.454 ± 0.037, n=20, t-test, p = 0.6613).",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using whole-cell patch clamp electrophysiology(C) Left: typical examples of evoked release upon action potential stimulation.",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using whole-cell patch clamp electrophysiology (D) Left: typical responses to hyperosmotic sucrose application (500 mM, 3.5 sec.) used to assess the RRP. Average RRP charge (M18WT: 1.68 ± 0.64 nC, n=13; M18Y473D: 0.08 ± 0.02 nC, n=10, t-test with Welch correction, p = 0.0274).",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using whole-cell patch clamp electrophysiology (E) Average Pves (EPSC charge / RRP charge) (M18WT: 6.75 ± 0.77%, n=13; M18Y473D: 0.24 ± 0.20%, n=10; Mann-Whitney U test, p < 0.0001).",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Autaptic munc18-1 null hippocampal neurons were rescued with a phosphomimetic Munc18-1 mutant, Y473D or wild-type Munc18-1 as control and assessed on morphology and synaptic transmission using whole-cell patch clamp electrophysiology (F) Left: example traces of spontaneous release of single SVs (mEPSCs). Average mEPSC frequency (M18WT: 20.18 ± 5.18 Hz, n=15; M18Y473D: 0.28 ± 0.13 Hz, n=17, Mann-Whitney U test, p < 0.0001), mEPSC amplitude (M18WT: 26.0 ± 1.7 pA, n=15; M18Y473D: 27.8 ± 2.2 pA, n=17, t-test, p = 0.5372) and mEPSC decay time (M18WT: 1.98 ± 0.10 ms, n=15; M18Y473D: 2.84 ± 0.41 ms, n=17, t-test with Welch correction, p = 0.0549).",
    "ncbi_link": "munc18-1: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples (A) Typical electron microscopy images from both groups. Scale bar = 100nm.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples (B) Average number of docked SV (M18WT: 7.63 ± 0.15 SVs; M18Y473D: 8.45 ± 0.20 docked SVs, multilevel analysis, p = 0.047).(B-E) M18WT : N=6 autaptic neurons, n=137 synapses; M18Y473D: N=8 autaptic neurons, n=116 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples ((C) Total number of SVs is not different (M18WT: 142 ± 11 SVs; M18Y473D: 148 ± 15 SVs, multilevel analysis, p = 0.456).(B-E) M18WT : N=6 autaptic neurons, n=137 synapses; M18Y473D: N=8 autaptic neurons, n=116 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples (D) The active zone (AZ) length is similar (M18WT: 561 ± 24 nm; M18Y473D: 646 ± 59 nm, multilevel analysis, p = 0.161).(B-E) M18WT : N=6 autaptic neurons, n=137 synapses; M18Y473D: N=8 autaptic neurons, n=116 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples (E) There is no change in the number of docked SVs per AZ length (M18WT: 14.0 ± 0.6 docked SVs/pm AZ; M18Y473D: 14.1 ± 0.9 docked SVs/pm AZ, multilevel analysis, p = 0.934). (B-E) M18WT : N=6 autaptic neurons, n=137 synapses; M18Y473D: N=8 autaptic neurons, n=116 synapses. ",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on chemically fixed samples (F) Typical electron microscopy images from both groups. Scale bar = 200nm.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on cryofixed samples (G) Average number of docked SV is equal (M18WT: 10.17 ± 0.38 SVs; M18Y473D: 10.75 ± 0.40 docked SVs, multilevel analysis, p = 0.264).(G-J) M18WT : N=3 independent cultures, n=159 synapses; M18Y473D: N=3 independent cultures, n=156 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on cryofixed samples (H) Total number of SVs is similar (M18WT: 160.2 ± 9.7 SVs; M18Y473D: 176.7 ± 9.2 SVs, multilevel analysis, p = 0.212).(G-J) M18WT : N=3 independent cultures, n=159 synapses; M18Y473D: N=3 independent cultures, n=156 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on cryofixed samples (I) The active zone (AZ) length is similar (M18WT: 740.2 ± 29.7 nm; M18Y473D: 771.4 ± 28.1 nm, multilevel analysis, p = 0.871).(G-J) M18WT : N=3 independent cultures, n=159 synapses; M18Y473D: N=3 independent cultures, n=156 synapses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Neurons expressing M18Y473D are not impaired at SV docking. Autaptic munc18-1 null hippocampal neurons expressing M18Y473D or M18WT as controls were analysed with electron microscopy on cryofixed samples ( (J) There is no change in the number of docked SVs per AZ length (M18WT: 14.36 ± 0.32 docked SVs/pm AZ; M18Y473D: 14.34 ± 0.32 docked SVs/pm AZ, multilevel analysis, p = 0.969). (G-J) M18WT : N=3 independent cultures, n=159 synapses; M18Y473D: N=3 independent cultures, n=156 synapses. ",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": " Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D. (A) Rundown of EPSC amplitude during 100 pulses at 10 Hz. Top: example traces of the current evoked by 40Hz stimulation. ",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(B) EPSC charge during 100 pulses at 40 Hz. Top: example traces of the current evoked by 40Hz stimulation. Insert shows total charge transferred during entire train (M18WT: 2.63 ± 0.38 nC; M18Y473D: 1.48 ± 0.24 nC, t test with Welch correction, p = 0.0177).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(C) Synaptic transmission was assessed before (naive(n)) and two seconds after (a) 40Hz stimulation. Average EPSC charge M18WT (naive: 70.9 ± 19.5 pC; after HFS: 75.4 ± 17.4 pC, n=12, paired t-test, p = 0.4049). Average EPSC charge M18Y473D (naive: 0.888 ± 0.342 pC, after HFS: 25.6 ± 9.3 pC, n=9, paired t-test, p = 0.0271).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(D) A hypertonic sucrose solution (500 mM, 3.5 sec.) was applied to release the RRP before (naive (n)) or two seconds after (a) HFS (100 pulses at 40 Hz).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(E) Quantification of RRP and Pves (EPSC charge / RRP charge * 100) from C-D. Average RRP size M18WT (naive: 1.73 ± 0.69 nC, after HFS: 1.34 ± 0.54 nC, n=12, paired t-test, p = 0.0557). Average RRP size M18Y473D (Naive: 0.061 ± 0.019 nC, after HFS: 0.207 ± 0.050 nC, n=9, paired t-test, p = 0.0246). Average Pves M18WT (naive: 7.07 ± 0.76 %, after HFS: 10.6 ± 1.6 %, n=12, paired t-test, p = 0.0201). Average Pves M18Y473D (naive: 0.27 ± 0.22 %, after HFS: 10.8 ± 2.2%, n=9, paired t-test, p = 0.0012).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Synaptic transmission was assessed during and immediately after sustained stimulation in autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473D.(F) PDBu application (1 µM) enhanced EPSC size in neurons expressing M18Y473D.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "(B) GST-Munc18-1 constructs were immobilized on glutathione beads and incubated with the indicated molar excess of Synaptobrevin/VAMP2 (over Munc18-1) for 1.5 h at 4°C. Bound Synaptobrevin/VAMP2 was analyzed by Western blot and immune decorating with an anti-Synaptobrevin/VAMP2 antibody and quantified by the LICORE system and ImageJ software. Synaptobrevin/VAMP2 bound to the GST-Munc18-1 mutants is represented as percentage of Synaptobrevin/VAMP2 bound to GST-Munc18-1 WT. Error bars indicate s.e.m., n=3.",
    "ncbi_link": "Munc18-1: 20910"
  },
  {
    "caption": "(E) Trans-SNARE Formation Assay: t- and v-SNARE SUVs were incubated in the presence or absence of different Munc18-1 constructs for 30min at 4°C. After solubilization and precipitation of the t-SNAREs using nickel beads, presence of full-length VAMP2 in the precipitates was probed by immunoblotting, which was used as an indicator for trans-SNARE assembly between SUVs.",
    "ncbi_link": "Munc18-1: 6812"
  },
  {
    "caption": "(A) Typical examples of single EPSCs. EPSC amplitude (M18WT: 2.98 ± 0.76 nA, n=11; M18Y473D: 0.042 ± 0.018 nA, n=11, M18Y473D/P335A: 2.02 ± 0.67 nA, n=7, Kruskal-Wallis test, p < 0.0004).",
    "ncbi_link": "M18: 20910"
  },
  {
    "caption": "Evoked and spontaneous release in autaptic munc18-1 null hippocampal neurons expressing M18Y473D, M18Y473D/P335A or wild-type Munc18-1 as control.(B) Typical traces of spontaneous release.",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Evoked and spontaneous release in autaptic munc18-1 null hippocampal neurons expressing M18Y473D, M18Y473D/P335A or wild-type Munc18-1 as control.(C) mEPSC frequency (M18WT: 8.23 ± 2.29 Hz, n=11; M18Y473D: 0.096 ± 0.056 Hz, n=8, M18Y473D/P335A: 2.18 ± 1.02 Hz, n=11, Kruskal-Wallis test, p = 0.2390), mEPSC amplitude (M18WT: 16.7 ± 1.0 pA, n=11; M18Y473D: 21.6 ± 5.2 pA, n=10, M18Y473D/P335A: 14.8 ± 1.2 pA, n=6, ANOVA, p = 0.1465) and decay time (M18WT: 2.53 ± 0.29 ms, n=11; M18Y473D: 3.79 ± 0.71 ms, n=10, M18Y473D/P335A: 2.85 ± 0.36 pA, n=6, Kruskal-Wallis test, p < 0.0003).",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Evoked and spontaneous release in autaptic munc18-1 null hippocampal neurons expressing M18Y473D, M18Y473D/P335A or wild-type Munc18-1 as control.(D) Depression of EPSC amplitude during a 10 Hz train. Inset shows first 4 pulses normalized to the first EPSC.",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": " Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology. (A) Evoked release upon action potential stimulation. Average EPSC amplitude (M18WT: 3.78 ± 0.58 nA, n=22; M18Y473F: 4.10 ± 0.61 nA, n=20, Mann-Whitney U test, p = 0.7915). Typical responses are depicted on the top. ",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(B) Average mEPSC frequency (M18WT: 5.42 ± 1.86 Hz, n=17; M18Y473F: 4.42 ± 1.01 Hz, n=14, t-test with Welch correction, p = 0.6424), mEPSC amplitude (M18WT: 20.72 ± 0.7 pA, n=17; M18Y473F: 20,5 ± 0.9 pA, n=14, t-test, p = 0.8373) and mEPSC decay time (M18WT: 2.54 ± 0.20 ms, n=17; M18Y473F: 2.46 ± 0.18 ms, n=14, t-test, p = 0.7550). Example traces of spontaneous release are depicted on top.",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(C) EPSC depression during 10 Hz stimulation is normal.",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(D) Depression of EPSC charge during 40 Hz stimulation is normal. Inset shows the first 5 pulses.",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(E) EPSC amplitude recovery two seconds after an RRP depleting 40 Hz train. Average EPSC recovery (M18WT: 82.2 ± 6.7 %, n=17; M18Y473F: 65.5 ± 11.0 %, n=12, t-test, p = 0.1805).",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(F) The amount of DSE-triggered EPSC depression was quantified by the ratio of the average EPSC amplitude (taken over 4 pulses given at 0.2 Hz) before or immediately following 10 seconds depolarization to 0mV. Typical EPSCs before and following DSE induction are depicted on the left. Average DSE (M18WT: 0.57 ± 0.04 fold, n=20; M18Y473F: 0.53 ± 0.04 fold, n=16, t-test, p = 0.5227).",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "Synaptic transmission in autaptic excitatory munc18-1 neurons expressing M18WT or a non-phosphorylatable Munc18-1 variant, M18Y473F, was tested with whole-cell patch clamp electrophysiology.(G) PDBu was bath applied during 0.05 Hz stimulation. Maximum potentiation of EPSC amplitude (M18WT: 2.56 ± 0.48 fold, n=7; M18Y473F: 2.82 ± 0.98 fold, n=8, t-test with Welch correction, p = 0.8168).",
    "ncbi_link": "munc18-1: 20910
M18: 20910
Munc18-1: 20910"
  },
  {
    "caption": "(A) Using denatured IP, Munc18-1 was pulled-down from cell lysate of HEK293T cells expressing M18WT or M18Y473A together with SFK kinases or an empty vector as control. Munc18-1 was then immunoblotted for tyrosine phosphorylation using the 4G10 antibody. The total amount of Munc18-1 was detected after stripping and reblotting for Munc18-1.",
    "ncbi_link": "M18: 6812"
  },
  {
    "caption": " (B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine. (B) Typical confocal images of neurons stained for MAP2, Synaptobrevin /VAMP2 and Munc18-1. Scale bar = 50πm.",
    "ncbi_link": "Munc18-1: 20910"
  },
  {
    "caption": "(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(C) Quantification of confocal images. Average synaptic Munc18-1 intensity (M18WT: 389 ± 85 a.u., n=21; M18Y473A: 321 ± 48 a.u., n=20, t-test with Welch correction, p = 0.4868), somatic Munc18-1 intensity (M18WT: 328 ± 49 a.u., n=21; M18Y473A: 245 ± 42 a.u., n=20, t-test, p = 0.2810), synapse number (M18WT: 129 ± 14, n=21; M18Y473A: 159 ± 16, n=20, t-test, p = 0.1548) and dendrite length (M18WT: 0.433 ± 0.028, n=21; M18Y473A: 0.461 ± 0.037, n=20, t-test, p = 0.5473).",
    "ncbi_link": "Munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(D) Evoked release upon action potential stimulation. Average EPSC amplitude (M18WT: 7.96 ± 0.94 nA, n=30; M18Y473A: 1.44 ± 0.34 nA, n=33, t-test with Welch correction, p < 0.0001). Typical responses are depicted on the right.",
    "ncbi_link": "Munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(E) Release by hyperosmotic sucrose application (500mM, 3.5sec.) was used to assess the RRP. Left: RRP charge (M18WT: 1.68 ± 0.64 nC, n=13; M18Y473A: 0.27 ± 0.08 nC, n=13, t-test with Welch correction, p = 0.0487). Typical responses are depicted in the middle. Right: vesicular release probability per neuron (EPSC charge / RRP charge). Mean Pves (M18WT: 6.75 ± 0.77%, n=13; M18Y473A: 1.98 ± 0.72%, n=13, t-test, p = 0.0001).",
    "ncbi_link": "Munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(F) Top: example traces of spontaneous release of single vesicles (mEPSCs). Average mEPSC frequency (M18WT: 20.18 ± 5.18 Hz, n=15; M18Y473A: 0.48 ± 0.15 Hz, n=20, t-test with Welch correction, p = 0.0019), amplitude (M18WT: 26.0 ± 1.7 pA, n=15; M18Y473A: 24.5 ± 1.6 pA, n=20, t-test, p = 0.5334) and decay time (M18WT: 1.98 ± 0.10 ms, n=15; M18Y473A: 2.13 ± 0.17 ms, n=20, t-test with Welch correction, p = 0.4499).",
    "ncbi_link": "Munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "(B-G) Munc18-1 null hippocampal neurons were rescued with wildtype Munc18-1a or a Munc18-1 mutant, Y473A, in which Y473 was replaced with alanine.(G) Typical electron microscopy images from rescued autaptic hippocampal Munc18-1 null neurons (scale bar = 100 nm). Neurons expressing M18Y473A have less synaptic vesicles (SV) docked at the number of docked SV. Average number of docked SV (M18WT: 7.63 ± 0.15 SVs; M18Y473A: 5.71 ± 0.28 SVs, multilevel analysis, p < 0.001), total number of SVs (M18WT: 142 ± 11 SVs; M18Y473A: 120 ± 12 SVs, multilevel analysis, p = 0.077), active zone (Munch et al.) length (M18WT: 561 ± 24 nm; M18Y473A: 501 ± 21 nm, multilevel analysis, p = 0.015) and docked SVs per AZ length (M18WT: 0.0140 ± 0.0006 docked SVs/nm AZ; M18Y473A: 0.0117 ± 0.0005 docked SVs/nm AZ, multilevel analysis, p = 0.003). M18WT : N=6 autaptic neurons, n=137 synapses; M18Y473A: N=8 autaptic neurons, n=136 synapses.",
    "ncbi_link": "Munc18-1: 20910
M18: 20910"
  },
  {
    "caption": " Autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473A were subjected to stimulation trains of 100 pulses at different frequencies. (A) Absolute EPSC amplitudes during a 10 Hz train. ",
    "ncbi_link": "M18: 20910
munc18-1: 20910"
  },
  {
    "caption": "Autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473A were subjected to stimulation trains of 100 pulses at different frequencies.(B) EPSC amplitudes during a 10 Hz train normalized to the first EPSC.",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473A were subjected to stimulation trains of 100 pulses at different frequencies.(C) Top: example traces of the currents evoked by 40 Hz stimulation. Bottom right: first 5 pulses of the 40 Hz train. Far right: transferred charge during 40 Hz train. Insert shows total charge transferred during entire 40 Hz train (M18WT: 2.63 ± 0.38 nC; M18Y473A: 2.93 ± 0.54 nC, t test, p = 0.6630).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473A were subjected to stimulation trains of 100 pulses at different frequencies.(D) EPSC augmentation is calculated by dividing the EPSC amplitude of a single pulse after a stimulation train by the amplitude of the first EPSC within this train. Mean augmentation after 5 Hz train (M18WT: 0.54 ± 0.05, n=8; M18Y473A: 2.88 ± 0.47, n=10; Unpaired t-test with Welch correction, p = 0.0008), 10 Hz train (M18WT: 0.70 ± 0.10, n=8; M18Y473A: 5.39 ± 0.77, n=10; Unpaired t-test with Welch correction, p = 0.0002) and 40 Hz train (M18WT: 0.93 ± 0.11, n=8; M18Y473A: 8.77 ± 1.52, n=10; Unpaired t-test with Welch correction, p = 0.0006).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Autaptic excitatory munc18-1 neurons expressing M18WT or M18Y473A were subjected to stimulation trains of 100 pulses at different frequencies.(E) A single action potential or sucrose application (500 mM, 3.5 sec.) was given before (naive) or two seconds after HFS (100 pulses at 40 Hz). Average EPSC charge M18WT (Naive: 70.9 ± 19.5 pC, after HFS: 75.4 ± 17.4 pC, n=12, Paired t-test, p = 0.4049). Average EPSC charge M18Y473A (naive: 10.3 ± 4.5 pC, after HFS: 46.2 ± 14.5 pC, n=13, Wilcoxon matched-pairs signed-ranks test, p = 0.0005). Average RRP size M18WT (naive: 1.73 ± 0.69 nC, after HFS: 1.34 ± 0.54 nC, n=12, paired t-test, p = 0.0557) Average HFS size M18Y473A (naive: 0.268 ± 0.075 nC, after HFS: 0.439 ± 0.107 nC, n=13, paired t-test, p = 0.0100). Average Pves M18WT (EPSC charge / RRP charge * 100) (Naive: 7.07 ± 0.76 %, after HFS: 10.6 ± 1.6 %, n=12, paired t-test, p = 0.0201). Average Pves M18Y473A (naive: 1.98 ± 0.72 %, 12.2 ± 2.8 %, n=13, paired t-test, p = 0.0021).",
    "ncbi_link": "munc18-1: 20910
M18: 20910"
  },
  {
    "caption": "Recovery of infectious recombinant MHV-GFP. Cell culture supernatants containing viruses produced after virus rescue from two MHV-GFP YAC clones (Clone1, Clone 2) were used to infect 17Cl-1 cells. At 48 hours post-infection, infected cells were visualised for GFP expression (left panels) and by bright field microscopy (right panels). Mock represents 17Cl-1 cells inoculated with supernatant from BHK-MHV-N cells electroporated without viral RNAs.",
    "ncbi_link": "viral RNA: "
  },
  {
    "caption": "Rescue of recombinant MERS-CoV and MERS-CoV-GFP. Following delivery of viral RNAs into BHK-21 cells via electroporation the cells were co-cultivated with VeroB4 cells and supernatants containing recombinant viruses produced were used to infect new VeroB4 cells. Infected cells were visualised by bright field microscopy for recombinant MERS-CoV (upper panel; 5 days post infection), and for GFP expression for recombinant MERS-CoV-GFP (lower panel, 3 days post infection). Mock represents VeroB4 cells inoculated with supernatant from BHK-21 cells electroporated without viral RNAs.",
    "ncbi_link": "GFP: 
viral RNAs: "
  },
  {
    "caption": "Rescue of recombinant rSARS-CoV-2 and rSARS-CoV-2-GFP. The experimental setting is illustrated in the upper panel. Two clones of each construct 1-6 were used to prepare YAC DNAs and in-vitro transcribed viral genome RNAs were electroporated into BHK-21 cells and/or BHK-SARS-N together with an mRNA encoding the SARS-CoV-2 N protein. Electroporated cells were co-cultivated with VeroE6 cells in a T25 flask and cell culture supernatants were transferred to 12-well plates to perform plaque assay for rSARS-CoV-2 constructs 1-3 and fluorescence microscopy for rSARS-CoV-2-GFP constructs 4-6. Plaque assays are shown in the lower panel for SARS-CoV-2 clones 1.1, 2.2, and 3.1. VeroE6 cells were infected with 10−1, 10−2, and 10−3 dilutions of 1 ml supernatant from the individual rescue experiments and are compared to non-infected cells (Mock). The expression of GFP in SARS-CoV-2-GFP infected VeroE6 cells is shown for clones 4.1, 5.2, and 6.1. Mock represents non-infected VeroE6 cells.",
    "ncbi_link": "GFP: 
viral genome RNA: 
N protein: 43740575"
  },
  {
    "caption": "U2Os cells co-transfected with YFP-FKBP and PCM1F2-Ce3-FRB, PACT-Ce3-FRB, or Ce3-FRB-Centrin2 were treated with rapamycin (100 nM). The translocation of YFP-FKBP onto PCM1F2- Ce3-FRB-labeled centriolar satellites, the PACT-Ce3-FRB-labeled pericentriolar matrix, and the Ce3-FRB-Centrin2-labeled centriolar lumen was monitored. The normalized fluorescence intensity of YFP-FKBP accumulation at centrosomes upon rapamycin (100 nM; blue) and DMSO (0.1%, vehicle control; red) treatment. Data are shown as the mean ± S.E.M. The graphs show immediate translocation of YFP-FKBP after rapamycin induction at centriolar satellites (left, n = 24 cells), the pericentriolar matrix (middle, n = 20 cells), and the centriolar lumen (right, n = 23 cells) from seven independent experiments.",
    "ncbi_link": "Ce3: 
Centrin2: 
FKBP: 
PACT: 
PCM1F2: 
YFP: "
  },
  {
    "caption": "U2Os cells co-transfected with each YFP-FKBP-labeled varisized probe (YFP-FKBP, YFP-FKBP-Grp1, YFP-FKBP-Luciferase, YFP-PSD95-FKBP, YFP-FKBP-β-Gals, YFP-FKBP-β-Galm, YFP-FKBP-ΔNβ-Gal, and YFP-FKBP-β-Gal) and Ce3-FRB with labels specific for centrosomal sub-compartments were treated with rapamycin (100 nM). The images of cerulean channel show centrosome sub-compartment from the untreated cells. Arrowheads indicate sites of centrosomes. Insets show higher-magnification images of the centrosomal regions. Dotted lines indicate the cell boundaries. The normalized fluorescence intensity of each probe at centriolar satellites (left, n = 14, 19, 17, 13, 11, 22, 14, and 9 cells from small to large probes), pericentriolar matrix (middle, n = 20, 19, 18, 16, 10, 18, 10, and 12 cells from small to large probes), and centriolar lumen (right, n = 10, 13, 13, 6, 3, 19, 13, and 9 cells from small to large probes) from 3-6 independent experiments.",
    "ncbi_link": "Ce3: 
FKBP: 
Grp1: 
Luciferase: 
PSD95: 
YFP: 
β-Gal: 
β-Galm: 
β-Gals: "
  },
  {
    "caption": "HeLa cells co-transfected with H2B-RFP (a chromosome marker), PACT-Ce3-FRB, and YFP-FKBP-Luciferase were sequentially incubated with thymidine (2 mM) for 16-18 hr and RO3306 (2.5 ng/mL) for 12 hr to synchronize cells in G2/M phase (Interphase cells in left panel). The probe trapping experiment in interphase cells was performed right after RO3306 washout. Anaphase cells were chosen for probe trapping experiment 45-60 min after RO3306 washout. Transfected cells in interphase or anaphase were treated with 100 nM rapamycin (Rapa). The centrosome regions are shown in lower panels. The normalized fluorescence intensity of YFP-FKBP-Luciferase accumulation at centrosomes in interphase (Green, n = 12 cells) or anaphase (Red, n =10 cells) cells upon rapamycin (100 nM) treatment.",
    "ncbi_link": "Ce3: 
FKBP: 
Luciferase: 
PACT: 
YFP: "
  },
  {
    "caption": "HeLa cells co-transfected with H2B-RFP (a chromosome marker), PACT-Ce3-FRB, and YFP-FKBP-Luciferase were synchronized in anaphase with or without CK666 treatment (0.4 mM). Rapamycin (100 nM) was added for 5 min to trigger the YFP-FKBP-Luciferase trapping at centrosomes. The right panel is the enlarged images of centrosome regions and arrows indicated centrosome sites. The percentage of cells in D exhibiting probe translocation. Data are shown as mean ± S.E.M. (n = 47 and 31 cells in DMSO and CK666 treated groups, respectively; 3-4 independent experiments).",
    "ncbi_link": "Ce3: 
FKBP: 
Luciferase: 
PACT: 
YFP: "
  },
  {
    "caption": "U2Os cells transfected with GCP4-GFP were treated with or without CK666 (0.4 mM, 2 hr) and then observed for the indicated time after photobleaching. The mobile fraction percentage (left) and mobile recovery half-time (right) of GCP4- GFP in FRAP experiments (c). Data (red) are shown as mean",
    "ncbi_link": "GCP4: 
GFP: "
  },
  {
    "caption": "Gene expression (Defa6, lysozyme) was measured via qPCR. P-values were calculated using 1-way ANOVA. All bars represent mean ± SEM. ****P< 0.0001; *** P<0.001; ** P≤ 0.01; * P≤ 0.05.",
    "ncbi_link": "Defa6: 13240
lysozyme: 17110"
  },
  {
    "caption": "TNFR1+/+ (n=9) and TNFR1-/- mice (n=11) were treated with 12.5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "TNFR1: 21937"
  },
  {
    "caption": "TLR4fl/fl mice (n=7) and TLR4VillinKO (n=9) mice were treated with 12.5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "TLR4: 21898
Villin: 22349"
  },
  {
    "caption": "TNFR1fl/fl mice (n=13) and TNFR1VillinKO (n=10) mice were treated with 12.5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "TNFR1: 21937
Villin: 22349"
  },
  {
    "caption": "TNFR1+/+ and TNFR1-/- mice (n=4-6) were treated with 12.5 mg/kg LPS. Ileum was isolated and gene expression was measured via qPCR. Fold changes are shown on the graph.",
    "ncbi_link": "TNFR1: 21937"
  },
  {
    "caption": "TNFR1fl/fl and TNFR1VillinKO mice (n=4-6) were treated with 12.5 mg/kg LPS. Ileum was isolated and gene expression was measured via qPCR. Fold changes are shown on the graph.",
    "ncbi_link": "TNFR1: 21937
Villin: 22349"
  },
  {
    "caption": "GRfl/fl (n=8,) and GRLysMKO mice (n=4) were treated with 2.5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "GRLysMKO mice were treated with PBS (n=12) or 10 mg/kg DEX (n=13) before a lethal dose of LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "TNF measurement in the serum of GRfl/fl (n=4) and GRLysMKO mice (n=3). Mice were treated with 2.5 mg/kg LPS and blood was drawn 2 hours later. TNF concentration was measured with ELISA.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "TNF measurement in the serum of GRfl/fl and GRLysMKO (n=4). Mice were treated with PBS or a lethal dose of LPS (12.5 and 2.5 mg/kg for GRfl/fl and GRLysMKO mice respectively) , with or without pre-treatment with 10 mg/kg DEX and blood was drawn 2 hours later. TNF concentration was measured with ELISA.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "GRfl/fl (n=4) and GRLysMKO mice (n=3-4) were treated with 2.5 mg/kg LPS. Ileum was isolated after 6 hours and gene expression was measured via qPCR. Fold changes are depicted on the graphs.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "GRfl/fl and GRLysMKO mice (n=4) were treated with a PBS or LPS (12.5 and 2.5 mg/kg for GRfl/fl and GRLysMKO mice respectively) with or without 10 mg/kg DEX pre-treatment of 30 minutes. Ileum was isolated after 6 hours and gene expression was measured via qPCR. Fold changes are depicted on the graphs.",
    "ncbi_link": "LysM: 17105
GR: 14815"
  },
  {
    "caption": "GRfl/fl (n=8) and GRVillinKO mice (n=10) were treated with 5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "GRVillinKO mice were treated with PBS (n=9) or 10 mg/kg DEX (n=10) before 5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "TNF measurement in the serum of GRfl/fl (n=4) and GRVillinKO mice (n= 4). Mice were treated with 5 mg/kg LPS and blood was drawn 2 hours later.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "TNF measurement in the serum of GRfl/fl (n=4) and GRVillinKO mice (n=4). Mice were treated with PBS or LPS (12.5 and 5 mg/kg for GRfl/fl and GRVillinKO mice respectively) with or without pre-treatment with 10 mg/kg DEX for 30 minutes. Blood was taken 2 hours after LPS challenge and TNF concentrations were measured with ELISA.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "GRVillinKO mice were treated with PBS (n=8) or a neutralizing P55 (TNFR1) antibody (n=9) 2 hours before and 8 hours after 5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "Ileum was isolated from non-stimulated GRfl/fl (n=4) and GRVillinKO mice (n=4) and gene expression was measured via qPCR. Expression levels are shown as fold induction with GRfl/fl expression values set at 1. P-values were calculated using a student's t-test.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "GRfl/fl (n=4) and GRVillinKO mice (n=4) were treated with 5 mg/kg LPS. Ileum was isolated and gene expression was measured via qPCR.",
    "ncbi_link": "GR: 14815
Villin: 22349"
  },
  {
    "caption": "Left: LPS dose-response curves of GRwt/wt (n=3-7 per LPS dose) and GRdim/dim mice (n=3-7 per LPS dose) treated with 1.5 mg/kg LPS. Right: LD50 values of LPS are depicted on top of each bar for each group.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GRdim/dim mice were treated with PBS (n=5) or 10 mg/kg DEX (n=5) before 1.5 mg/kg LPS and survival was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "TNF measurement in the serum of GRwt/wt (n=5) and GRdim/dim mice (n= 5). Mice were treated with 1.5 mg/kg LPS and blood was drawn 2 hours later. TNF concentration was measured with ELISA.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "TNF measurement in the serum of GRwt/wt and GRdim/dim mice (n=4) treated with PBS or LPS (12.5 and 1.5 mg/kg in GRwt/wt and GRdim/dim mice respectively) with or without pretreatment with 10 mg/kg DEX. Blood was taken 2 hours after LPS challenge and TNF concentrations were measured with ELISA.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GRdim/dim mice were treated with PBS (n=6) or a neutralizing P55 (TNFR1) antibody (n=8) 2 hours before and 8 hours after 1.5 mg/kg LPS and lethality was monitored. P-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Tofacitinib (n=6) or vehicle (n=7) was given orally to GRdim/dim mice. After 1.5 mg/kg LPS injection survival was monitored and p-values were analyzed with a Fisher's exact test.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GRwt/wt (n=4) and GRdim/dim (n=4) mice were treated with 1.5 mg/kg LPS. Ileum was isolated and gene expression was measured via qPCR. Fold changes are depicted on the graphs.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GRdim/dim mice (n=4) were treated with PBS or 1.5 mg/kg LPS with or without 10 mg/kg DEX pretreatment. Ileum was isolated and gene expression was measured via qPCR. Fold changes are depicted on the graphs.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "(D) RipAC overexpression inhibits flg22-triggered MAPK activation in Arabidopsis. 100 nM flg22Pto was used to treat Arabidopsis seedlings and the samples were collected at indicated time points. Immunoblots were analysed using anti-pMAPK and anti-RipAC antibodies. Coomassie brilliant blue (CBB) staining and a non-specific band were used as loading control. Molecular weight (kDa) marker bands are indicated for reference.",
    "ncbi_link": "RipAC: 2831203"
  },
  {
    "caption": "(E) flg22-triggered MAPK activation in pub4 T-DNA mutants. 100 nM flg22Pto was used to treat Arabidopsis seedlings and the samples were collected at indicated time points for western blots. Immunoblots were analyzed using anti-pMAPK and anti-FLS2 antibodies. Coomassie brilliant blue (CBB) staining was used as loading control. Molecular weight (kDa) marker bands are indicated for reference.",
    "ncbi_link": "pub4: 816846"
  },
  {
    "caption": "(B) Co-immunoprecipitation of PUB4 and BIK1 in N. benthamiana. PUB4-GFP or GFP-LTI6b were transiently co-expressed with BIK1-HA in the leaves of N. benthamiana. After treatment with mock or 1 μM flg22Paer for 10 min, total proteins (input) were extracted and subjected for immunoprecipitation with anti-GFP beads.",
    "ncbi_link": "GFP: 
HA: 
LTI6b: 
BIK1: 818549
PUB4: 816846"
  },
  {
    "caption": "(C) Co-immunoprecipitation of PUB4 with PRR complex members in Arabidopsis. PUB4 co-immunoprecipitated with FLS2 and BAK1 specifically after 10 min of 1 μM flg22Paer treatment, and constantly with BIK1. Total protein extracts (input) from Col-0 and PUB4-FLAG plants were subjected to immunoprecipitation with anti-FLAG beads.",
    "ncbi_link": "FLAG: 
PUB4: 816846"
  },
  {
    "caption": "RipAC does not affect PUB4 association with PRR complex members. PUB4-FLAG, PUB4-FLAG RipAC-GFP and Col-0 plants were treated for 10 min with water (as mock) or 1 μM flg22Paer and elf18Ecol treatment. Total protein extracts (input) were subjected for immunoprecipitation with anti-FLAG beads. Immunoblots were analyzed using the indicated antibodies. Molecular weight (kDa) marker bands are indicated for reference. Data information: The experiment was performed 3 times with similar results.",
    "ncbi_link": "FLAG: 
GFP: 
RipAC: 2831203
PUB4: 816846"
  },
  {
    "caption": "(A) Analysis of BIK1-HA protein accumulation in BIK1-HA+/-, pub4-/- BIK1-HA+/-, and PUB4-FLAG+/- BIK1-HA+/- in 4- to 5-week-old plants. Prior to protein extraction leave disks were treated for 6 h with 100 mM MG132, 50 mM CHX, and for 10 min with water (as mock) or 1 mM flg22Paer. Proteins were extracted in SDS buffer and analysed by western blot. BAK1 was used as a loading control. Numbers correspond to the quantitation of the BIK1-HA band, normalized to the quantitation of the BAK1 control band in the same sample.",
    "ncbi_link": "FLAG: 
HA: 
BIK1: 818549
PUB4: 101259015
pub4: 816846"
  },
  {
    "caption": "(B) BIK1-HA accumulation is reduced in PUB4-FLAG+/- BIK1-HA+/- line compared to BIK1-HA+/- line in the absence of PAMP treatment. Total protein extracts were analysed by western blot. Tubulin was used as a loading control.",
    "ncbi_link": "FLAG: 
HA: 
BIK1: 818549
PUB4: 816846"
  },
  {
    "caption": "(E) BIK1-HA accumulation is reduced in RipAC-GFP/BIK1-HA line compared to Col-0/BIK1-HA line. Total protein extracts were analysed by western blot. Actin was used as a loading control.",
    "ncbi_link": "GFP: 
HA: 
BIK1: 818549
RipAC: 2831203"
  },
  {
    "caption": "(A) Representative images of GFP‐LC3 staining in HCT116 XIAP WT and XIAP KO cells with stable expression of GFP‐LC3. Quantification of LC3 punctate cells was shown on the right. The data are represented as means±s.d. of three independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557
XIAP: 8257"
  },
  {
    "caption": "(B) Endogenous LC3 expression in HCT116XIAP WT and XIAP KO cells was analysed by western blotting with anti‐LC3 antibody. The data are representative of three biological replicates. The ratio of LC3II/LC3I to actin is presented in Supplementary Figure S1A.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(C) Lysates from XIAP+/+ and XIAP−/− mouse embryonic fibroblasts were analysed by western blotting with the indicated antibodies. The data are representative of two biological replicates.",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "(D) Autophagic vesicles in HCT116 XIAP WT and XIAP KO cells were evaluated by electron microscopy. The images are representative of three biological replicates.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(F) HCT116 XIAP KO cells were treated with Embelin as indicated. LC3‐II accumulation was determined by western blot analysis with anti‐LC3 antibody. The data are representative of three biological replicates.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(H) MEF ATG5 WT and ATG5 KO cells were individually transfected with XIAP‐specific or control siRNAs. Forty‐eight hours after transfection, cell lysates were analysed by western blotting with the indicated antibodies. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S1E.",
    "ncbi_link": "ATG5: 11793
XIAP: 11798"
  },
  {
    "caption": "(I) HCT116XIAP WT and XIAP KO cells were treated with 20 ‐μM Z‐VAD‐FMK or DMSO for 2 h. Cell lysates were then analysed by western blotting. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S1F.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(J) HCT116 XIAP KO cells were transfected with either Flag‐XIAP (D148A/W310A) or control plasmid. Twenty‐four hours after transfection, cell lysates were subjected to western blot analysis with the indicated antibodies. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S1G.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(A) A549 and IMR90 cells were transfected with XIAP‐specific or control siRNAs. Cell lysates were subjected to western blot analysis with the indicated antibodies. The data are representative of two biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S2A.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(B) HCT116 cells expressing XIAP‐specific or control siRNAs, HCT116 XIAP WT and XIAP KO cells were individually transfected with Flag‐XIAP or control vector. Cell lysates were analysed by western blotting. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S2D.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(C) HCT116 XIAP WT and XIAP KO cells were individually transfected with Flag‐XIAP or control vector. Cytoplasmic/nuclear fractionation was performed to analyse cellular localization of Mdm2 and p53. PARP and GAPDH were used as nuclear (N) and cytoplasmic (C) fraction markers, respectively. The data are representative of three biological replicates.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(D) HCT116 p53+/+ and p53−/− cells were individually transfected with XIAP‐specific or control siRNAs. LC3 conversion was detected by western blot analysis. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S2E.",
    "ncbi_link": "p53: 7157
XIAP: 8257"
  },
  {
    "caption": "(E) HCT116 p53+/+ and p53−/− cells were individually transfected with Flag‐XIAP or control vector. LC3 conversion was detected by western blot analysis. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S2F.",
    "ncbi_link": "p53: 7157
XIAP: 8257"
  },
  {
    "caption": "(F) HCT116 XIAP WT and XIAP KO cells treated with 10 μM Nutlin3 for 6 h. LC3 conversion was evaluated by western blot analysis. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S2H.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(G) HCT116 XIAP KO cells were treated with the indicated amounts of Nutlin for 8 h. Cell lysates were analysed by western blotting with anti‐LC3 antibody. The data are representative of three biological replicates.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(C) HCT116 cells were treated with XIAP‐specific or control siRNAs. Twenty‐four hours later, cells were cultured in the presence of 50 μg ml−1 cycloheximide for the indicated periods of time, and subsequently analysed by western blotting. We should mention that amounts of cell lysates were adjusted to achieve similar expression levels of Mdm2 at time 0, while the same amounts of cell lysates were used to examine levels of XIAP and actin. The data are representative of three biological replicates. The ratio of Mdm2 to actin is presented in Supplementary Figure S3B.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(D) p53−/−Mdm2−/− MEF cells were co‐transfected with the indicated Mdm2, XIAP, and p53 constructs. Cell lysates were analysed by western blotting with the indicated antibodies. We should mention that XIAP H467A expressing plasmid was always used less than XIAP expressing plasmid to ensure expression levels of XIAP and XIAP H467A were similar. The data are representative of three biological replicates.",
    "ncbi_link": "Mdm2: 17246
p53: 22059
XIAP: 11798"
  },
  {
    "caption": "(E) p53−/−Mdm2−/− MEF cells were transfected with the indicated plasmids. Twenty‐four hours after transfection, cells were treated with 20 μM MG‐132 for additional 4 h. Cell lysates were denatured before proteins conjugated to His‐ubiquitin were pulled down by Ni2+‐NTA beads. The bead‐bound proteins and total cell lysates (TCLs) were analysed by western blot with anti‐Mdm2 antibody. The data are representative of three biological replicates.",
    "ncbi_link": "Mdm2: 17246
p53: 22059"
  },
  {
    "caption": "(F) In all, 2 μM Mdm2 or its C464A mutant and 1 μM XIAP or its H467A mutant proteins were incubated with 100 nM E1, 2 μM E2 and 200 μM Ub in a total 20 μlin vitro ubiquitination reaction buffer at 37°C for 1 h. The reaction mixtures were analysed by western blotting with anti‐Mdm2 antibody. The data are representative of three biological replicates.",
    "ncbi_link": "Mdm2: 4193
XIAP: 8257"
  },
  {
    "caption": "(G) p53−/−Mdm2−/− MEF cells were transfected with the indicated plasmids. Cell lysates were analysed by western blotting. The data are representative of three biological replicates.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "(A) HCT116 XIAP WT and XIAP KO cells were treated with EBSS for the indicated periods of time. GFP‐LC3 puncta formation was observed by a microscope. Quantification of LC3 punctate cells was shown on the right. The data are represented as means±s.d. of three independent experiments.",
    "ncbi_link": "LC3: 440738///81631///84557
XIAP: 8257"
  },
  {
    "caption": "(B) HCT116 XIAP WT and XIAP KO cells were treated with EBSS for 4 h followed by western blot analysis with the indicated antibodies. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S6B.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(C) HCT116 XIAP WT and XIAP KO cells were treated with 1 μM API‐2 for 6 h. Cell lysates were analysed by western blotting. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S6C.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(F) HCT116 XIAP KO cells were transfected with Flag‐XIAP, Flag‐XIAP S87A, Flag‐XIAP S87D or control vector. Twenty‐four hours after transfection, cells were harvested. LC3 conversion was evaluated by western blot analysis. The data are representative of three biological replicates. The ratio of LCII/LC3I to actin is presented in Supplementary Figure S6D.",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(G) p53−/−Mdm2−/− MEF cells were transfected with HA‐Mdm2 plus Flag‐XIAP, Flag‐XIAP S87A or Flag‐XIAP S87D. Twenty‐four hours later, cells were treated with 20 μM MG-132 for another 4h. Cell lysates were subjected to immunoprecipitation with anti‐HA antibody. Immunoprecipitates were analysed by western blotting. The data are representative of two biological replicates.",
    "ncbi_link": "Mdm2: 17246
p53: 22059
XIAP: 11798"
  },
  {
    "caption": "(A-C) 1 × 106HCT116XIAP WT and 1 × 106XIAP KO cells (group 1), 1 × 106HCT116XIAP KO cells (KO‐Ctrl) and 1 × 106HCT116XIAP KO cells stably expressing wild‐type XIAP (KO‐XIAP) (group 2), 1 × 106HCT116XIAP KO cells (KO‐Ctrl) and 1 × 106HCT116XIAP KO cells stably expressing XIAP S87A mutant (KO‐XIAP SA) (group 3), or 1 × 106HCT116XIAP KO cells (KO‐Ctrl) and 1 × 106HCT116XIAP KO cells stably expressing XIAP S87D mutant (KO‐XIAP SD) (group 4) were individually injected to the left flank (Left) and right flank (Right) of nude mice as indicated. Five weeks after injection, the mice were sacrificed and photographed (A). The volumes of all flank tumours excised from six mice in each group were compared (n=6) (B). Tumour weights were represented as means±s.d. from six mice in each group (C).",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "(D-F) 1 × 106HCT116XIAP KO cells or 1 × 106HCT116XIAP KO cells stably expressing XIAP D148A/310A were injected to the right flank of nude mice as indicated (n=3). Five weeks after injection, the mice were sacrificed and photographed (D). The volumes of excised tumours were shown (E). Tumour weights were represented as means±s.d. from three mice in each group (F).",
    "ncbi_link": "XIAP: 8257"
  },
  {
    "caption": "To verify the specificity of Cx43-CreERT mice for astrocytes, mice were crossed to a tdTomato reporter line to induce Cre-dependent tdTomato expression after tamoxifen administration. TdTomato fluorescence was enhanced with an antibody against red fluorescent protein, and astrocytes were stained with antibodies against GFAP or S100β (not shown). Merged images and quantification show efficient and widespread tdTomato expression specific for astrocytes (arrowheads) in 8-month and 11-month old animals. Expression was small in neurons (stained with NeuN, not shown) and negligible in NG2 cells and oligodendrocytes. Scale bars, 250 µm (upper panel) and 50 µm (lower panel).",
    "ncbi_link": "tdTomato: 
Cre: 2777477
ERT: 2099
Cx43: 14609"
  },
  {
    "caption": "The majority of peri-plaque astrocytes in APP/PS1-Stat3WT were positive for activated/phosphorylated Stat3 (pStat3) in the cortex (Cx) and hippocampus (HC), whereas the fraction of pStat3-positive astrocytes was significantly lower in APP/PS1-Stat3KO mice in both regions (n = 8 mice (3 females and 5 males) per group; age, 8 months; Mann-Whitney test). The occurrence of pStat3 in WT-Stat3KO and WT-Stat3WT mice was negligible (n = 8 mice (4 females and 4 males) per group; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Examples of Stat3 activation in APP/PS1-Stat3KO and APP/PS1-Stat3WT. D, pStat3 (arrowheads) was abundantly present in reactive astrocytes (identified by GFAP) around plaques (identified by IC16). E, only few astrocytes were positive for pStat3 in APP/PS1-Stat3WT mice. Scale bars, 50 µm.",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Overall astrocytic and microglial coverage, as assessed by GFAP and Iba1 stainings, remained unchanged in APP/PS1-Stat3WT vs. APP/PS1-Stat3KO mice (n = 8 mice (4 females and 4 males) per group; age, 8 months; Mann-Whitney test for each comparison). Scale bars, 500 µm.",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "The volume of peri-plaque reactive astrocytes was increased by the Stat3 deletion (Mann-Whitney test), and there was a nonsignificant trend towards more astrocytes branches and junctions and longer total process length (Mann-Whitney test; APP/PS1-Stat3WT, n = 5 (2 female and 3 male) mice; APP/PS1-Stat3KO, n = 7 (3 female and 4 male) mice; age, 8-10 months). Scale bar, 20 µm.",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Microglial volume was not affected by the Stat3 deletion (Mann-Whitney test), but peri-plaque microglia had significantly more microglial branches and junctions per plaque, and the total process length of peri-plaque microglia was increased (Mann-Whitney test; same mice as in C-D). Scale bar, 20 µm.",
    "ncbi_link": "Stat3: 20848"
  },
  {
    "caption": "Aβ plaque burden, as assessed by plaque load and size using an anti-Aβ antibody, was strongly reduced in APP/PS1-Stat3KO vs. APP/PS1-Stat3WT mice (Mann-Whitney test; scale bar, 300 µm).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Plaque density, assessed by staining brain sections with thioflavin (yellow), remained unchanged in APP/PS1-Stat3KO vs. APP/PS1-Stat3WT mice (Mann-Whitney test; scale bar, 250 µm).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Microglia (left Y axes) from APP/PS1 mice internalized significantly more Aβ positive for IC16 when Stat3 was deleted in astrocytes (Mann-Whitney test), whereas no changes were seen in astrocytes (right axes; APP/PS1-Stat3WT, n = 8 (4 female and 4 male) mice; APP/PS1-Stat3KO, n = 11 (5 female and 6 male) mice; age, 11 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Microglia (left Y axes) from APP/PS1 mice internalized significantly more Aβ positive for methoxy-XO4 when Stat3 was deleted in astrocytes (Mann-Whitney test), whereas no changes were seen in astrocytes (right axes; APP/PS1-Stat3WT, n = 8 (4 female and 4 male) mice; APP/PS1-Stat3KO, n = 11 (5 female and 6 male) mice; age, 11 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Western Blot quantification of protein levels of the Aβ-degrading enzymes neprilysin/CD10 and CD36, as well as the Aβ-binding apoliprotein E (apoE) revealed a significantly increased expression of neprilysin and CD36 and a decreased expression of apoE (APP/PS1-Stat3WT, n = 9 (5 female and 4 male) mice; APP/PS1-Stat3KO, n = 9 (5 female and 4 male) mice; age, 11 months; Mann-Whitney test for all comparisons). In contrast, TREM2 expression remained unchanged (APP/PS1-Stat3WT, n = 8 (4 female and 4 male) mice; APP/PS1-Stat3KO, n = 7 (4 female and 3 male) mice; age, 11 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Western Blot of protein levels of the Aβ-degrading enzymes neprilysin/CD10 and CD36, as well as the Aβ-binding apoliprotein E (apoE) revealed a significantly increased expression of neprilysin and CD36 and a decreased expression of apoE (APP/PS1-Stat3WT, n = 9 (5 female and 4 male) mice; APP/PS1-Stat3KO, n = 9 (5 female and 4 male) mice; age, 11 months; Mann-Whitney test for all comparisons). In contrast, TREM2 expression remained unchanged (APP/PS1-Stat3WT, n = 8 (4 female and 4 male) mice; APP/PS1-Stat3KO, n = 7 (4 female and 3 male) mice; age, 11 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Quantitative PCR from cortex of APP/PS1-Stat3KO compared to APP/PS1-Stat3WT mice revealed lower expression of 'A1' markers Amigo2 and C3, whereas Ggta1 remained unchanged. In turn, the 'A2' marker Tm4sf1 was upregulated and there was a nonsignificant trend for a higher expression of B3gnt5 (n = 6 mice (3 females and 3 males) per group; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "Amigo2: 105827
APP: 351
B3gnt5: 108105
C3: 12266
Ggta1: 14594
PS1: 5663
Stat3: 20848
Tm4sf1: 17112"
  },
  {
    "caption": "Confirming lower expression of the 'A1' marker C3d, western blot analysis indicated lower protein levels of C3d in APP/PS1-Stat3KO. APP/PS1-Stat3WT, n = 6 (2 female and 4 male) mice; APP/PS1-Stat3KO, n = 6 (3 female and 3 male) mice; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Immunohistochemistry using an antibody against C3d revealed that lower expression of C3d particularly occurred in peri-plaque reactive astrocytes (arrows; plaques were visualized with methoxy-XO4, arrowheads; scale bars, 50 µm; APP/PS1-Stat3WT, n = 6 (2 female and 4 male) mice; APP/PS1-Stat3KO, n = 6 (3 female and 3 male) mice; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Whole-brain levels of the pro-inflammatory cytokines IL-1β and TNF-α were significantly reduced in APP/PS1-Stat3KO mice (Mann-Whitney test), whereas no changes were seen for IL-10 (APP/PS1-Stat3WT, n = 13 (6 female and 7 male) mice; APP/PS1-Stat3KO, n = 13 (8 female and 5 male) mice; age, 11 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "These changes were paralleled by a decrease in the area covered by dystrophic neurites in APP/PS1-Stat3KO compared to APP/PS1-Stat3WT mice, as assessed by LAMP1 staining (Mann-Whitney test; n = 10 male mice for both groups; age, 8 months; scale bars, 300 µm).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Calcium imaging of anesthetized animals showed that the hyperactivity of astrocytes in APP/PS1-Stat3KO mice was reduced to levels comparable to WT-Stat3WT mice, but significantly increased in APP/PS1-Stat3WT mice (One-Way ANOVA followed by Bonferroni's multiple comparison test; n = 6 mice (3 female and 3 male) for each group; age, 8 months).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Similarly, neuronal activity was also reduced to levels comparable to WT-Stat3WT mice in APP/PS1-Stat3KO mice, but significantly increased in APP/PS1-Stat3WT mice (One-Way ANOVA followed by Bonferroni's multiple comparison test; same mice as in B). The cumulative distributions of neuronal calcium transients in APP/PS1-Stat3KO mice were not different from those of WT-Stat3WT mice (p = 0.31, Kolmogorov-Smirnov test), but significantly different from those of APP/PS1-Stat3WT mice (p = 0.001, Kolmogorov-Smirnov test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Two-photon imaging of these mice confirmed that astrocytic hyperactivity were reduced by MRS2179 (APP/PS1-Stat3WT, n = 6 (4 female and 2 male) mice; APP/PS1-Stat3KO, n = 6 (2 female and 4 male) mice; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Two-photon imaging of these mice confirmed that propagating calcium waves were reduced by MRS2179 (APP/PS1-Stat3WT, n = 6 (4 female and 2 male) mice; APP/PS1-Stat3KO, n = 6 (2 female and 4 male) mice; age, 8 months; Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "MRS2179 (APP/PS1-Stat3WT, n = 6 (4 female and 2 male) mice; APP/PS1-Stat3KO, n = 6 (2 female and 4 male) mice; age, 8 months; Mann-Whitney test). This network normalization induced a reduction of activated Stat3 (pStat3) in astrocytes assessed in fixed brain sections of the same mice (Mann-Whitney test). Scale bars, 50 µm.",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "Spatial learning and memory were assessed in the Morris Water Maze paradigm. APP/PS1-Stat3KO mice showed faster latencies to reach the hidden platform compared with APP/PS1-Stat3WT on days 4 and 5, but were similar to WT-Stat3WT and WT-Stat3KO mice (Two-way repeated-measures ANOVA followed by Bonferroni post-hoc test; P values are for APP/PS1-Stat3KO vs. APP/PS1-Stat3WT mice).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "The area under the curve (AUC) for the latency to reach the hidden platform was similar in APP/PS1-Stat3WT compared to WT-Stat3WT and WT-Stat3KO mice, but significantly higher in APP/PS1-Stat3KO mice (Kruskal-Wallis test followed by Dunn's multiple comparisons test).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "In the probe trial 24 h after the last training day, the time mice spent in the target quadrant (TQ) was different from chance in all groups except for APP/PS1-Stat3WT mice (p < 0.05, one-tailed one-sample t test). APP/PS1-Stat3KO, WT-Stat3WT and WT-Stat3KO mice spent significantly more time in the target quadrant compared to the mean of all other quadrants (AO), whereas APP/PS1-Stat3WT spent equal times in the target and all other quadrants (Wilcoxon matched-pairs signed rank test for each comparison; APP/PS1-Stat3WT, n = 15 (8 female and 7 male) mice; APP/PS1-Stat3KO, n = 15 (9 female and 6 male) mice; age, 8-9 months).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "APP/PS1 mice were systemically treated with SH-4-54 for 6 weeks and compared to age-matched APP/PS1 mice treated with vehicle. In the Morris Water Maze test, treatment with SH-4-54 led to significantly faster latencies to reach the hidden platform on the last training day (Two-way repeated-measures ANOVA followed by Bonferroni post-hoc test).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "The area under the curve (AUC) for the latency to reach the hidden platform was also smaller in APP/PS1 mice treated with the Stat3 inhibitor (Mann-Whitney test).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "In the probe trial test, APP/PS1 mice treated with the Stat3 inhibitor spent significantly more time in the target quadrant (TQ) compared to the mean of all other quadrants (AO), whereas APP/PS1 mice treated with vehicle spent equal times in the target and all other quadrants (Wilcoxon matched-pairs signed rank test for all comparisons; APP/PS1-Stat3WT, n = 12 (5 female and 7 male) mice; APP/PS1-Stat3KO, n = 12 (4 female and 8 male) mice; age, 8 months).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "While no changes were seen in morphological parameters of peri-plaque astrocytes, there was a significant increase in the process length of near-plaque microglia, indicating higher microglial complexity (Mann-Whitney test for all comparisons; APP/PS1-Stat3WT, n = 12 (6 female and 6 male) mice; APP/PS1-Stat3KO, n = 12 (7 female and 5 male) mice; age, 8 months).",
    "ncbi_link": "APP: 351
PS1: 5663
Stat3: 20848"
  },
  {
    "caption": "E. 10-fold serial dilutions of chm7Δapq12Δ strains grown at the indicated temperatures with either an empty pRS416 plasmid (-) or those expressing the indicated Chm7 constructs (pRS416-HA-CHM7, pRS416-HA-chm7-NTD, pRS416-HA-chm7-CTD). See Appendix Figure S2A for protein levels.",
    "ncbi_link": "apq12: 854771
chm7: 853398"
  },
  {
    "caption": "A. Deconvolved inverted fluorescence micrographs Chm7-GFP and truncations in the indicated null strains. Scale bar is 5 μm.B. Plot of the percentage of cells with SD of Chm7-GFP (and truncations) NE foci from A. Data are from 3 independent replicates where >200 cells were counted for each strain. p values from un-paired student's T-test. ** is a p value ≤ 0.01; ****, p ≤ 0.0001.",
    "ncbi_link": "Chm7: 853398"
  },
  {
    "caption": "C. Deconvolved inverted fluorescence micrographs of Chm7-GFP in a heh1Δ strain containing either an empty pRS426 plasmid (-) or those expressing HEH1 (pRS426-HEH1) or HEH2 (pRS426-HEH2).D. Plots of the percentage of cells from C with Chm7-GFP NE-foci. Data are from 3 independent replicates where >200 cells were counted for each strain. Error bars are SD. p values from T-test. **, p ≤ 0.01; ****, p ≤ 0.0001.",
    "ncbi_link": "HEH2: 852069
HEH1: 854974
heh1: 854974"
  },
  {
    "caption": "C. GST, GST-Snf7 and GST-snf7OPEN were immobilized on GT-resin and incubated with buffer(-) or recombinant heh2(1-308)-His6. Bound proteins separated by SDS-PAGE were visualized by coomassie stain and by Western blot with anti-His6 antibody and ECL detection (WB; top panel). Middle panel shows indicated cropped region of gel where contrast has been increased. Numbers on side of gel show position of molecular weight (MW) markers.",
    "ncbi_link": "heh2: 852069
snf7: 850712"
  },
  {
    "caption": "D. In vitro transcription translation (IVT) reactions generating radiolabeled (35S) truncations of Heh2 (inputs) were incubated with bead-bound GST, GST-snf7OPEN or GST-Snf7 before washing, elution and detection of bound proteins by autoradiography (top panel) or coomassie staining (bottom).",
    "ncbi_link": "snf7: 850712"
  },
  {
    "caption": "E. As in C except with GST-Chm7 constructs. Upper panel shows western blot (WB) with anti-His6 antibody. *chm7-NTD is also expressed with a His6 tag. Bottom panel is coomassie stained.",
    "ncbi_link": "chm7: 853398"
  },
  {
    "caption": "F. Deconvolved inverted fluorescence micrographs of Heh1-VN Snf7-VC BiFC signal in a chm7Δ strain with either an empty plasmid (\"-\"; pRS416) or one expressing CHM7 (pRS416-HA-CHM7). Cell borders outlined. Scale bar is 5 μm.G. Plot of the percentage of cells with BiFC signal from F. Error bars are SD from the mean of each replicate. p values from un-paired student's T-test where ns is p > 0.05. ***, p ≤ 0.001.",
    "ncbi_link": "chm7: 853398
CHM7: 853398"
  },
  {
    "caption": "B. Deconvolved fluorescence images of SINC-containing nuclei in vps4Δ and vps4Δpom152Δ cells expressing Chm7-GFP and Nup170-mCherry (green, red and merged images are shown). Scale bar is 1 μm.",
    "ncbi_link": "pom152: 855159
vps4: 856303"
  },
  {
    "caption": "D. Deconvolved fluorescence micrograph showing the lack of colocalization of Chm7-GFP and clustered Nup170-mCherry in a nup133Δ strain. Scale bar is 1 μm.",
    "ncbi_link": "nup133: 853957"
  },
  {
    "caption": "A. Plot of the percentage of nup116Δ cells incubated for 3 h at 37°C with nuclear rim-like accumulations of Chm7-GFP. Error bars are SD from the mean from 3 independent replicates of >100 cells. p values from unpaired student's T-test where *** is p ≤ 0.001.B. Deconvolved inverted fluorescence micrographs of Chm7-GFP in nup116Δ cells at either 23°C or grown for 3 h at 37°C. Percentages ± SD of the proportion of cells with Chm7-GFP NE foci are shown under each panel (see Figure EV5F).",
    "ncbi_link": "nup116: 855066"
  },
  {
    "caption": "C. Electron micrographs showing herniations of the NE in nup116Δ cells after incubation for 3 h at 37°C. N denotes nuclear interior. Scale bars are 100 nm.",
    "ncbi_link": "nup116: 855066"
  },
  {
    "caption": "A. Deconvolved fluorescence micrographs of NLS-GFP in the indicated yeast strains at either 30°C or after 2 h at 37°C. Scale bar is 5 μm.B. Plot of the mean nuclear to cytosolic fluorescence intensity ratio of NLS-GFP from cells represented in A. Error bars are SD from the mean from 3 independent replicates of 150 cells from each strain. p values from un-paired student's T-test where ns is p > 0.05; **, p ≤ 0.01; ****, p ≤ 0.0001. Only chm7Δ and chm7Δapq12Δ cells have N:C ratios below 1.2 (dotted red line).C. Re-plotting of data from B showing the percentage of cells with a N:C NLS-GFP fluorescence ratio <1.2. Error bars are the SD from the mean from 3 independent replicates of 150 cells/strain. p values from student's T-test where *, p ≤ 0.05; **, p ≤ 0.01; ****, p ≤ 0.0001.",
    "ncbi_link": "apq12: 854771
chm7: 853398"
  },
  {
    "caption": ". Co-immunoprecipitation analysis of the HOIP K784R mutant with SHARPIN and HOIL-1L using total cell extracts of HEK293T cells transiently expressing Myc-HOIP wildtype (WT), or Myc-HOIP-K784R with HOIL-1L-HA and Flag-SHARPIN. Anti-Vinculin antibody used to monitor protein loading. Representative data shown from three independent experiments.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
HOIL-1L: 55072
HOIP: 55072
SHARPIN: 81858"
  },
  {
    "caption": ". Immunoblotting to detect ubiquitination of NEMO in HEK293T cells transiently expressing Flag-NEMO, GFP-SHARPIN, and HOIL-1L-HA with Myc-HOIP wildtype (WT), Myc-HOIP K784R or Myc-HOIP C885A. Total cell lysates in denaturing conditions subjected to SDS-PAGE followed up by immunoblotting using antibodies as indicated. Anti-Vinculin antibody to monitor loading. Representative data from three independent experiments.",
    "ncbi_link": "Flag: 
GFP: 
HA: 
Myc: 
NEMO: 
HOIL-1L: 55072
HOIP: 55072
SHARPIN: 81858"
  },
  {
    "caption": "Immunoblotting to detect TNF-induced degradation and phosphorylation of IκB-α, or phosphorylation of IKK in immortalized Hoip+/+ and HoipK778R/K778R MEFs treated with human TNF (20ng/ml) for the indicated times. Immunoblots of anti-Vinculin antibody and anti-α-Tubulin antibody shown for monitoring loading amount. Representative data from three independent experiments",
    "ncbi_link": "Hoip: 268749"
  },
  {
    "caption": "TNF-dependent induction of Caspase 3 activation in immortalized Hoip+/+ or HoipK778R/K778R MEFs measured by using DEVD-AFC. MEFs treated with hTNF (100ng/ml) and CHX (1µg/ml) for 4 hours subjected to the Caspase 3 activity assays.",
    "ncbi_link": "Hoip: 268749"
  },
  {
    "caption": "TNF-induced Caspase 8 activity in Hoip+/+ or HoipK778R/K778R immortalized MEFs treated with hTNF (100ng/ml) with or without Cycloheximide (CHX) (1µg/ml) or z-VAD (20µM). Representative data from three independent experiments, n=4.",
    "ncbi_link": "Hoip: 268749"
  },
  {
    "caption": "(B) Confocal fluorescence microscopy of 293T cells transfected with 0.5 μg pQCXIP encoding IFITM3 variants containing N-terminal FLAG (pQCXIP-FLAG-IFITM3) and immunostained with anti-FLAG M2 antibody. Scale bar, 5 μm.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(E) SDS-PAGE of Opti-prep purified supernatants (25 ng p24 equivalent) derived from 293T cells transfected with pQCXIP-FLAG-IFITM3 variants, HIV-1 pNL4-3, and Vpr-Blam plasmid followed by immunoblotting with anti-FLAG M2 and anti-p24 Gag (183-H12-5C).",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(F) Opti-prep purified supernatants from (E) were incubated with SupT1 target cells for 4 hours and virus-cell fusion was scored by flow cytometry. Mean + SD of 5-10 experiments (each performed with virus produced from an independent transfection) is shown. (G) Virus used in (E) were used to infect SupT1 cells and productive infection was scored at 48-60 hours by immunostaining with the KC57 antibody and flow cytometry. Expression of pCMV-MxA served as a negative control. The mean + SD of 5-10 experiments is shown.",
    "ncbi_link": "MxA: 4599"
  },
  {
    "caption": "(H) Confocal fluorescence microscopy of 293T cells transfected with 0.5 μg pQCXIP-FLAG-IFITM3 variants and immunostained with anti-FLAG M2 antibody",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(J) SDS-PAGE of Opti-prep purified supernatants (25 ng p24 equivalent) derived from 293T cells transfected with pQCXIP-FLAG-IFITM3 constructs, HIV-1 pNL4-3, and Vpr-Blam plasmid followed by immunoblotting with anti-FLAG M2 and anti-p24 Gag. Scale bar, 5 μm.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(A) Confocal fluorescent microscopy of SupT1 T cells transduced with Tet-inducible pQCXIP-FLAG-IFITM3 or pQCXIP-FLAG-IFITM3 Δ1-21 (Tet-ON) immunostained with anti-FLAG M2 antibody following overnight treatment with 500 ng/mL doxycycline. Scale bar, 10 μm.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(B) Tet-ON SupT1 cell lines were treated or not with 500 ng/mL doxycycline overnight and induction of IFITM3 protein was assessed anti-FLAG M2 immunostaining and flow cytometry.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(C) Tet-ON SupT1 cell lines were productively infected with NL4-3 VSV-G and then treated with 500 ng/mL doxycycline overnight to produce virus from IFITM3- and IFITM3+ cells. 25 ng p24 equivalents of purified were used to infect fresh Tet-ON SupT1 cells cell targets, which were previously treated with 500 ng/mL doxycycline or not. Infection was scored at 72h post-infection by immunostaining with KC57 and flow cytometry. Mean + SD of 3 experiments are shown.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(E) 293T cells were transfected with the indicated amount of pQCXIP-FLAG-IFITM3 or pQCXIP-FLAG-Δ1-21 or pCMV-MxA and 1.0 μg of HIV-1 pNL4-3. SDS-PAGE was performed on whole cell lysates followed by immunoblotting with anti-FLAG M2, anti-p24 Gag, anti-Env gp120 (NIH #288), and anti-tubulin antibodies. Western blot images are representative of 3 independent experiments. Unpaired t-test, *p<0.05, ♯p=0.12, non statistically significant. Comparisons were made between the condition indicated and the correponding condition in Tet-ON IFITM3 cells.",
    "ncbi_link": "IFITM3: 10410
MxA: 4599"
  },
  {
    "caption": "(A) Confocal fluorescence microscopy of 293T cells transfected with 0.5 μg of pQCXIP-FLAG-Human IFITM3 mutated at indicated residues and immunostained with anti-FLAG M2 antibody. Scale bars, 5 μm. The P17L, P18H, Δ22-24, P18L/L23P and P18H/Δ19-23 mutations were introduced into the human IFITM3 background.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(B) SDS-PAGE of FLAG-immunoprecipitated fractions from 293T cells following transfection of 0.5 μg of pQCXIP-FLAG-IFITM3 variants and 0.5 μg of pCI-HA-NEDD4 or pCI-HA-NEDD4 C867A. Immunoblotting was performed with anti-FLAG M2, anti-IFITM3 (Abcam, EPR5242), and an anti-ubiquitin antibody (Enzo Life Sciences, recognizing K29-, K48-, and K63-linked mono- and polyubiquitinylated proteins). 'L' indicates the presence of light chain antibody derived from the FLAG antibody-coupled beads used for immunoprecipitation. *, **, and *** indicate mono-, di-, and tri-ubiquitinated forms of IFITM3.",
    "ncbi_link": "IFITM3: 10410
NEDD4: 4734"
  },
  {
    "caption": "(D) 293T cells were transfected with 1.0 μg of pNL4-3 and 0.5 μg of pQCXIP-FLAG-IFITM3 variants. Virus-containing supernatants were harvested and 10 ng p24 equivalents were used to reinfect fresh SupT1 T cells. Productive infection was scored by immunostaining with the KC57 antibody and flow cytometry at 48 hours post-infection. The means + SD of 3 experiments are shown.",
    "ncbi_link": "IFITM3: 10410"
  },
  {
    "caption": "(E) 2.0 x 10ˆ5 cells were seeded and challenged with 10 ng of HIV-1NL4-3 in the presence of 2 μg/mL DEAE-Dextran. Productive infection was scored by immunostaining with KC57 and flow cytometry at 48 hours post-infection. The 'Colobus native' sequence represents the full IFITM3 sequence identified in the colobus monkey. (F) As in (E), except cells were challenged with Influenza A virus H1N1 PR/8/34, (Charles River Laboratories), at a dose that resulted in ˜50% infection of control (Empty) cells (equivalent to 103 TCID50 / 0.2 mL). Infection was scored by immunostaining with an anti-IAV NP antibody and flow cytometry at 18 hours post-infection. Results are presented in a logarithmic scale. Means + SD of 3-5 experiments are shown. Unpaired t-test, *p<0.05, **p<0.005.",
    "ncbi_link": "IFITM3: "
  },
  {
    "caption": "(B) Locomotor behavior, measured by thrashing rates in liquid medium, in the C. elegans strains with neuronal expression of human WT SOD1 or ALS-linked mutant SOD1G85R, in the presence (M1/M1) or absence (+/+) of the suppressor mutation (n = 16).",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(C) Northern (top panel) and western (middle, bottom panels) blot analyses of total RNA and protein from SOD1G85R strains, with (M1/M1) or without (+/+) suppressor mutations, demonstrating that the levels of SOD1G85R mRNA and total protein are not changed by the suppressor mutation (M1/M1). The western blot lanes are from the same gel and exposure.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "(F) Locomotor behavior, measured by thrashing rates, of the C. elegans carrying the SOD1G85R transgene on the normal background (WT), with the null mutation of either ufd-2(tm1380) or spr-5(by134), the double mutation ufd-2(tm1380);spr-5(by134), or the M1 suppressor ufd-2(W824X);spr-5(R646Q) (n = 16).",
    "ncbi_link": "SOD1: 6647
spr-5: 173214
ufd-2: 174295"
  },
  {
    "caption": "(G) Western blotting of the supernatant (S) and pellet (P) protein fractions from the C. elegans carrying the SOD1G85R transgene with the double mutation ufd-2(tm1380);spr-5(by134) compared with controls. While SOD1G85R protein levels are unchanged in the S fraction, those in the P fraction are decreased in the double suppressor mutant. The P fraction represents only about 1.7% of total SOD1G85R in the WT sample; therefore, a higher ratio of the P fraction relative to the S fraction (approximately 2:1) is used for the western analysis.",
    "ncbi_link": "SOD1: 6647
spr-5: 173214
ufd-2: 174295"
  },
  {
    "caption": "(H) The overexpression (OE) of WT UFD-2 or SPR-5 in the C. elegans nervous system blocks the protection conferred by the double mutation ufd-2(tm1380);spr-5(by134) (n = 16). Data represent means ± SEM. The numerical data used to make this figure can be found in S1 Data.",
    "ncbi_link": "spr-5: 173214
SPR-5: 173214
ufd-2: 174295
UFD-2: 174295"
  },
  {
    "caption": "(A) Top: schematic drawing depicts pan-neuronal expression of YFP in head and ventral neurons in the context of the C. elegans body plan. Left: micrographs show the SOD1G85R-YFP proteins expressed in WT or the spr-5(by134);ufd-2(tm1380) mutant background. The double-mutant worms show a marked decrease in protein aggregation in neurons. Enlarged sections of headneurons (red framed) and ventral cord neurons (white framed) are shown. Middle: quantification of locomotion in the spr-5(by134);ufd-2(tm1380) and the WT C. elegans with neuronal expression of SOD1G85R-YFP (n = 30). Right: a decrease in the protein levels of SOD1G85R-YFP in the presence of spr-5(by134);ufd-2(tm1380) is shown by western blots of the supernatant (S) and the pellet (P) fractions. (B and C) Analyses of the spr-5(by134);ufd-2(tm1380) and the WT C. elegans with neuronal expression of TDP-43-c25-YFP (n = 30) or PolyQ-YFP (n = 12) as in (A).",
    "ncbi_link": "SOD1: 6647
spr-5: 173214
ufd-2: 174295"
  },
  {
    "caption": "(D) Neurodegenerative rough-eye phenotype in adults is alleviated by the knockdown of the Drosophila homologs of ufd-2/UBE4B and spr-5/LSD1-CG9934 and Su(Var)3-3, respectively, compared to the control (CTRL). Eye-specific expression of TDP-43M337V, FUSR521C, and RNA interference (RNAi) was driven by GMR-Gal4.",
    "ncbi_link": "GMR-Gal4: 
CG9934: 34699
FUS: 2521
LSD1: 23028
spr-5: 173214
Su(Var)3-3: 40217
TDP-43: 23435
UBE4B: 10277
ufd-2: 174295"
  },
  {
    "caption": "(A) Western blots of cell lysates derived from mock (CTRL), single UBE4B or LSD1, or double UBE4B and LSD1 knockdowns. Supernatant (S) and pellet (P) fractions were probed with indicated antibodies. While the LSD1 or UBE4B single-knockdown reduces the SOD1G85R aggregates in both supernatant and pellet fractions, the combined knockdown produces the strongest reduction in the aggregates. (B) Quantification of SOD1G85R protein levels by western blotting (A). n = 3 (supernatant); n = 8 (pellet).",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(C) Western blots of a representative cycloheximide chase experiment to determine SOD1 protein half-lives in the double UBE4B and LSD1 knockdown cells versus controls. (D) Quantification of SOD1G85R clearance, as analyzed by western blotting in (C). The graph indicates the relative band intensity of SOD1G85R at each chase time point. n = 5; Overall p = 0.02 (paired t test, CTRL versus UBE4B and LSD1 double knockdown). Individual p = 0.03 (3 h), p = 0.003 (6 h), p = 0.06 (9 h), and p = 0.004 (12-21 h).",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(E) The half-life of SOD1G85R is reduced from 8.5 h to 5 h upon knockdown of UBE4B and LSD1. Data represent means ± SEM. The numerical data used to make this figure can be found in S1 Data.",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(B) The volcano scatter plot indicates fold changes in the levels of gene transcripts affected differentially by the UBE4B and LSD1 double knockdown versus control shRNA. Gray spots represent 22,148 annotated transcripts. Red spots are predicted p53-activated targets, and blue spots are predicted p53-inhibited targets. The enrichment of red spots in the up-regulated genes (right upper quadrant, >1.2-fold change, p ≤ 0.04) and blue spots in the down-regulated genes (left upper quadrant) indicates that the p53-mediated transcription is activated by the UBE4B and LSD1 double knockdown.",
    "ncbi_link": "LSD1: 23028
p53: 7157
UBE4B: 10277"
  },
  {
    "caption": "C) RT-qPCR validation of the expression levels of representative p53 target genes in the UBE4B and LSD1 double-knockdown samples. n = (2 to 6), p ≤ 0.04.",
    "ncbi_link": "LSD1: 23028
p53: 7157
UBE4B: 10277"
  },
  {
    "caption": "(D) The p53 protein level is significantly increased by UBE4B and LSD1 double knockdown. Left: representative western blots showing p53 levels, the knockdown of UBE4B and LSD1, and the actin control in HEK293T cells. Right: quantification of the p53 protein levels normalized against actin (n = 3).",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "E) The p53-mediated transcriptional activity is measured by a luciferase reporter under the control of a p53-response element promoter, which was transfected into HEK293T cells 72-96 h after the initiation of the UBE4B and LSD1 single or double knockdowns (n = 6).",
    "ncbi_link": "LSD1: 23028
p53: 7157
UBE4B: 10277"
  },
  {
    "caption": "(F) Increased interaction of p53 with its activating partner 53BP1 in response to UBE4B and LSD1 knockdown. Left: representative western blots of 53BP1 co-immunoprecipitation. Right: quantification of the 53BP1 co-immunoprecipitation (n = 2). Data represent means ± SEM.",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(G) RT-qPCR validation of the expression levels of FOXO3a, FOXO4, and PSMD11 (n = 6).",
    "ncbi_link": "FOXO3a: 2309
FOXO4: 4303
PSMD11: 5717"
  },
  {
    "caption": "(H) The FOXO3a-mediated transcriptional activity was measured with a luciferase reporter under the control of a FOXO-response element promoter. HEK293T cells were transfected with shRNAs for control, LSD1, UBE4B, or both LSD1 and UBE4B, followed by transfection of the luciferase reporter together with a constitutively active form of FOXO3a (TM) 72-96 h later (n = 6). Data represent means ± SEM. The numerical data used to make this figure can be found in S1 Data.",
    "ncbi_link": "FOXO3a: 2309
LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(A) Increased protein levels of proteasome subunits upon the UBE4B and LSD1 double knockdown in HEK293T cells",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": ". (B) The UBE4B and LSD1 single or double knockdowns increase the proteasomal degradation of a reporter substrate, Suc-LLVY-Luciferin, whose degradation is measured in a luciferase release assay. The double knockdown shows synergistic proteasomal activation when compared with the individual knockdowns (n = 6).",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(C) The autophagy activity is significantly increased in cells with the UBE4B and LSD1 double knockdown. The in vivo activity of the ATG4B protease, which cleaves LC3 precursors, was quantified via a Gaussia luciferase release assay (see S5D Fig., S5E Fig., and Materials and Methods for details). The HCT116 cells were analyzed 48 h after the initiation of the knockdown.",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(D) Quantification of LC3-II levels in HEK293T cells with the UBE4B and LSD1 double knockdown or the mock control. The cells were treated with or without 10 mM 3-methyladenine (3-MA) for 48h before lysis. Western blots indicate an increase in LC3 levels (top panels) in the double UBE4B and LSD1 knockdown cells (middle panels), while the actin control is unchanged (bottom panels). The graph shows the quantification of LC3-II levels as normalized to actin levels (n = 3). A one-way ANOVA test with matched multiple comparisons and Tukey correction was used for statistics. Data represent means ± SEM. The numerical data used to make this figure can be found in S1 Data.",
    "ncbi_link": "LSD1: 23028
UBE4B: 10277"
  },
  {
    "caption": "(A) p53 small molecule activators Tenovin-1 and CP-31398 reduce the levels of misfolded SOD1 proteins, as determined by the SOD1G85R solubility assay in HEK293 cells. Increasing concentrations of the p53 activators significantly decrease the levels of SOD1G85R but not the endogenous WT SOD1 proteins in western blots of both supernatant and pellet fractions.",
    "ncbi_link": "SOD1: 6647
p53: 7157"
  },
  {
    "caption": "(B) A decrease in p53 as the result of shRNA knockdown increases the levels of SOD1G85R but not WT SOD1 proteins in the SOD1G85R aggregation assay, as shown by western blots of both supernatant (S) (n = 2) and pellet (P) (n = 3) fractions.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C) A complete absence of p53 increases the accumulation of SOD1G85R mutant proteins in p53-/- HCT116 cells when compared with controls. Representative western blots (left panels) and quantification of SOD1G85R levels in the supernatant lysates are shown. The middle graph indicates the ratio of G85R to WT SOD1 proteins in the presence or absence of p53 with varying amounts of transfected mutant SOD1. The right graph panel shows the same data as shown in the middle panel, but normalized to the average SOD1G85R level for each amount of the transfected plasmid. Data represent means ± SEM. The numerical data used to make this figure can be found in S1 Data.",
    "ncbi_link": "SOD1: 6647
p53: 7157"
  },
  {
    "caption": "(A) Left: p53 knockdown reverses the enhanced clearance of SOD1G85R proteins conferred by the UBE4B and LSD1 double knockdown. Total amounts of shRNAs were adjusted to be equal with nontargeting CTRL shRNAs. Right: quantification of insoluble aggregated SOD1G85R in pellet fractions from HEK293T cells transfected with control, double (UBE4B/LSD1), or triple (UBE4B/LSD1/p53) shRNAs (n = 2).",
    "ncbi_link": "LSD1: 23028
SOD1: 6647
p53: 7157
UBE4B: 10277"
  },
  {
    "caption": "(B) The degenerative TDP-43M337V eye phenotype is exacerbated by the knockdown of the Drosophila homolog of p53 (p53 RNAi), or by the overexpression of a dominant-negative p53 mutant (p53.R155H). Expression of p53 RNAi, p53.R155H, and TDP-43M337V are driven by GMR-Gal4.",
    "ncbi_link": "GMR-Gal4: 
p53: 2768677
TDP-43: 23435"
  },
  {
    "caption": "(C) The p53-activating drug Tenovin-1 (TEN1) protects spinal cord motor neurons from SOD1G85R-induced proteotoxicity. Rat spinal cord cultures were grown as described in Materials and Methods and treated with 0.8 μM TEN1 or vehicle (VEH) DMSO, followed by infection of HSV-SOD1G85R or the HSV-LacZ control after 24 h. At day 5 post-infection, cells were fixed and stained with a motor neuron-specific anti-neurofilament H (NF-H) antibody. Left: representative images of motor neurons in each condition. Scale bar = 50 μm. Right: quantification of motor neuron survival (one-way ANOVA with multiple comparisons and Tukey correction). Data represent means ± SEM.",
    "ncbi_link": "LacZ: 
SOD1: 6647
p53: 24842"
  },
  {
    "caption": "Survival curves for control (n=23 biological replicates), Rorc(t)CreTg Tet1/3fl/fl(n=20 biological replicates), Rorc(t)CreTg Tet1/2/3fl/fl mice (n=10 biological replicates). Paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Representative H&E staining of the lungs (top panel) and small intestine (bottom panel) and histopathological scoring of 3 months old control (n=3 biological replicates) and Rorc(t)CreTg Tet1/3fl/fl mice (n=3 biological replicates). Data are means +/-SEM, One-Way ANOVA with uncorrected Fisher's LSD test. Scale bar = 263 and 53 µm, top and bottom panels, respectively. , Paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Absolute number of FoxP3+ Tregs from the thymus (n=5 or 7 biological replicates) and spleen (n=7 or 8 biological replicates) of control Tet1/3fl/fl and Rorc(t)CreTg Tet1/3fl/fl mice. Data is means +/- SEM, unpaired Mann-Whitney t test. Paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Quantification of CD25 MFI expression on FoxP3+ T cells in the spleen of control Tet1/3fl/fl (n=4 biological replicates) and Rorc(t)CreTg Tet1/3fl/fl mice (n=4 biological replicates). Data is means +/- SEM, unpaired Mann-Whitney t test. Paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Quantification of FoxP3 MFI expression on FoxP3+ T cells in the spleen of control Tet1/3fl/fl (n=6 biological replicates) and Rorc(t)CreTg Tet1/3fl/fl mice (n=6 biological replicates). Data is means +/- SEM, unpaired Mann-Whitney t test.   Quantification of ICOS MFI expression on FoxP3+ T cells from the mesenteric lymph nodes of control Tet1/3fl/fl (n=5 biological replicates) and Rorc(t)CreTg Tet1/3fl/fl (n=7 biological replicates) mice. Data is means +/- SEM, unpaired Mann-Whitney t test.   , Paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Weight curve of female Rag-/- mice after T-cell transfer colitis induced via transfer of naïve WT CD45.1 conventional CD4+ T cells alone (n=5 recipients) or in combination with Tregs isolated from Tet1/3fl/fl and Rorc(t)CreTg Tet1/3fl/fl littermates (n=5 recipients/group). Data is means +/- SEM, Two-Way ANOVA with Geisser-Greenhouse correction. Experiment was replicated 2 times.",
    "ncbi_link": "Cre: 2777477
CD45.1: 19264
Rag: 19373
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Representative flow plots and quantification of percent Tbet+, Rorγt+ and FoxP3+ of CD45.1 CD4+ effector cells isolated from the MLN of female Rag-/- mice 7 weeks post T cell transfer induced colitis. Respective cohorts were Naïve CD45.1 T cells only (n=5 mice), WT CD45.1+ Tet1/3fl/fl Tregs (n=5 mice) and WT CD45.1+Rorc(t)CreTg Tet1/3fl/fl Tregs (n=4 mice). Cells were pre-gated on Live CD45.1+TCRβ+ cells. Data is means+/- SEM, Two-Way ANOVA with Tukey's Multiple comparison test. Experiment was replicated 2 times.",
    "ncbi_link": "Cre: 2777477
CD45.1: 19264
Rag: 19373
Rorc: 19885
Tet1: 52463"
  },
  {
    "caption": "Quantification of Live CD4+ FoxP3+ T cells absolute cell numbers in different organs of FoxP3Cre Tet1/3+/+ (n=3 biological replicates) and FoxP3Cre Tet1/3 fl/fl (n=3 biological replicates) male littermate mice. Data is shown as means+/- SEM, One-Way ANOVA with uncorrected Fisher's LSD test.",
    "ncbi_link": "Cre: 2777477
FoxP3: 20371
Tet1: 52463"
  },
  {
    "caption": "Quantification of CD25-FoxP3lo, CD25+FoxP3- and CD25+FoxP3+ cells among Live CD73-CD4+ T cells thymocytes of control Tet3fl/fl (n=5 biological replicates) and Rorc(t)CreTg Tet3fl/fl mice (n=3 biological replicates) mice. Data is shown as means+/- SEM, Two-Way ANOVA with Sidak's multiple comparison test. Quantification of CD25-FoxP3lo, CD25+FoxP3- and CD25+FoxP3+ cells among Live CD73-CD4+ T cells thymocytes of control Tet1fl/fl (n=6 biological replicates) and Rorc(t)CreTg Tet1fl/fl mice (n=6 biological replicates). Data is shown as means+/- SEM, Two-Way ANOVA with Sidak's multiple comparison test. paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Tet1: 52463
Tet3: 194388"
  },
  {
    "caption": "Quantification of Nur77 staining among TCRβhi CD69+ CD4 SP thymocytes from control Tet3fl/fl (n=5 biological replicates) and Rorc(t)CreTg Tet3fl/fl mice (n=3 biological replicates). Data is as means+/- SEM, unpaired two-tailed Mann-Whitney t-test Quantification of Nur77 staining among TCRβhi CD69+ CD4 SP thymocytes from control Tet1fl/fl (n=4 biological replicates) and Rorc(t)CreTg Te1fl/fl mice (n=3 biological replicates). Data is shown as means+/- SEM, unpaired two-tailed Mann-Whitney t-test paired male or female mice were used and no gender biases associated with genotypes were observed.",
    "ncbi_link": "Cre: 2777477
Rorc: 19885
Te1: 52463
Tet1: 52463
Tet3: 194388"
  },
  {
    "caption": "IL-2 mRNA quantification by qPCR in CD4+ T cells post-activation at indicated time-points (n=2 biological replicates/genotype). Cells were stimulated with anti-CD3/CD28 without exogenous IL-2 or TGF-β. Data is shown as means+/-SEM, Two-Way ANOVA with Sidak's multiple comparison test",
    "ncbi_link": "IL-2: 16183"
  },
  {
    "caption": "Integrated genome viewer (IGV) browser tracks of the Lck, Fyn gene loci highlighting differential accessible regions (in red boxes) in biological replicates of CD4+ T cells activated with anti-CD3/CD28 and 20 ng/mL TGF-β +/- 100U IL-2.",
    "ncbi_link": "Fyn: 14360
Lck: 16818"
  },
  {
    "caption": "Integrated genome viewer (IGV) browser tracks of the Itk gene loci highlighting differential accessible regions (in red boxes) in biological replicates of CD4+ T cells activated with anti-CD3/CD28 and 20 ng/mL TGF-β +/- 100U IL-2.",
    "ncbi_link": "Itk: 16428"
  },
  {
    "caption": "(G) IGV browser track of the IL-2 locus showing accessibility peaks at the IL-2 promoter region and upstream of the promoter (red arrow) in biological replicates of CD4+ T cells activated as in (B).",
    "ncbi_link": "IL-2: 16183"
  },
  {
    "caption": "(L) Larval NSCs of control (ctrl; yw), pr-set7716/Df, and UAS-pr-set7 induced with insc­-Gal4 at 72h ALH were stained for Pr-set7, Mira and DNA. (M, N) Quantifications of NSC diameters (M) at 24h ALH and EdU incorporation (N) for genotypes in (O). In (M), n=152 for control; n=129 for pr-set7716/Df. In (N), for control, n=601, 13 BL at 24h ALH; n=988, 14 BL at 48h ALH; n=813, 9 BL at 72h ALH and n=829, 10 BL at 96h ALH. For pr-set7716/Df, n=566, 12 BL at 24h ALH; n=808, 13 BL at 48h ALH; n=1032, 10 BL at 72h ALH and n=825, 9 BL at 96h ALH. Data information: Quantification data are presented in as mean ± SD M, N). n numbers in N) were total NSCs counted with total brain lobes measured, while each brain lobe considered as one biological replicate. White arrows point to NSCs Statistical analyses were done comparing two different genotypes using Mann-Whitney test M, N). ***P < 0.001. Scale bars, 5 μm L),",
    "ncbi_link": "Gal4: 855828
pr-set7: 41743"
  },
  {
    "caption": "(C) Larval NSCs of control (ctrl; yw), pr-set7716/Df, pr-set7716/Df with UAS-pr-set7 induced with insc-Gal4, and pr-set7716/Df with pr-set7-BAC at 24h ALH were stained for H4K20me1, Dpn, Mira and DAPI. Control: n=108; pr-set7716/Df: n=87; pr-set7716/Df with UAS-pr-set7 induced with insc-Gal4: n=167 and pr-set7716/Df with pr-set7-BAC: n=104. Data information: White arrows point to NSCs. Scale bars, 5 μm",
    "ncbi_link": "Gal4: 855828
pr-set7: 41743"
  },
  {
    "caption": "(E) Larval NSCs with FUCCI constructs induced with insc-Gal4 at 24h were stained for GFP, RFP, Dpn, and Prospero (Pros). (F) Quantifications of quiescent NSCs in different cell-cycle stages from FUCCI flies (induced with insc-Gal4) in control (and insc-Gal4>FUCCI) and pr-set7716/Df. Quiescent NSCs of insc-Gal4>FUCCI: 76.1%±1.5% in G2, 1.7%±0.2% in S and 22.2%±1.3% in G0 (n=343). Quiescent NSCs of insc-Gal4>FUCCI; pr-set7716/Df: 74.4%±1.0% in G2, 0.9%±0.2% in S and 24.7%±0.8% in G0 (n=344). Data information: Quantification data are presented in as mean ± SD Statistical analyses were done comparing two different genotypes using Mann-Whitney test ns: non-significant. White arrows point to NSCs. Scale bars, 5 μm",
    "ncbi_link": "Gal4: 855828
pr-set7: 41743"
  },
  {
    "caption": "(D) qPCR analysis of pr-set7, cdk1, ebd1 and arm in larval brains of control (ctrl; yw) and pr-set7716/Df(3R)ED5644 (716/Df) at 24h ALH. n=7 as biological replicates. Statistical analyses were done comparing between control (GAPDH1, GAPDH2, Tbp1 and Rpl32) and pr-set7716/Df, using Mann-Whitney test. The mRNA levels of control were normalized to 1. Data are presented as mean ± SD calculated from all replicates. Data information: Data are presented in (D, as mean ± SD. Statistical analyses were done comparing two different genotypes using Mann-Whitney test (D *P < 0.05",
    "ncbi_link": "GAPDH1: 
GAPDH2: 
Rpl32: 
Tbp1: 
arm: 31151
cdk1: 34411
ebd1: 38082
pr-set7: 41743"
  },
  {
    "caption": "G) Larval NSCs of control (ctrl; yw) and pr-set7716/Df at 24h ALH were stained for Ebd1, Dpn and Mira. Yellow dotted boxes, zoomed-in area. White arrows point to NSCs. Data information: Scale bars, 15 μm (G).",
    "ncbi_link": "pr-set7: 41743"
  },
  {
    "caption": "(H, I) Quantifications of nuclear Ebd1 (H) and the corrected total cell fluorescence (CCF) (I) In (H), n=756, 9 BL for control; n=765, 9 BL for pr-set7716/Df. In (I), CCF = Integrated Density - (Area of selected cell × Mean fluorescence of background readings). CCFs were 1102.2±493.2 (n=99) for control (ctrl; yw) and 144.0±88.0 (n=98) for 716/Df. Data information: Data are presented in , I, s mean ± SD. n numbers in (H) were total NSCs counted with total brain lobes measured, while each brain lobe was considered as one biological replicate. Statistical analyses were done comparing two different genotypes using Mann-Whitney test , H, I, ***P < 0.001.",
    "ncbi_link": "pr-set7: 41743"
  },
  {
    "caption": "(H) Larval brains of control (ctrl; yw), cdk1-Myc overexpression under insc­-Gal4, pr-set7716/Df(3R)ED5644 (716/Df), and pr-set7716/Df with cdk1-Myc induced with insc-Gal4 at 24h ALH were labelled with Dpn and EdU. (I, J) Quantifications of EdU incorporation (I) and NSC diameters (J) for genotypes in (H). In (I), n=1334, 16 BL for control; n=1299, 15 BL for insc>cdk1; n=1221, 18 BL for pr-set7716/Df and n=1372, 16 BL for pr-set7716/Df with cdk1-Mycinduced with insc-Gal4. In (J), n=153 for control; n=152 for insc>cdk1; n=156 for pr-set7716/Df and n=159 for pr-set7716/Df with cdk1-Myc induced with insc-Gal4.Data information: Data were presented in quantification graphs as mean ± SD I, J). n numbers in I) were total NSCs counted with total brain lobes measured, while each brain lobe was considered as one biological replicate. Statistical analyses were done comparing among different genotypes using ordinary one-way ANOVA ***P < 0.001. Scale bars, 30 μm H). Control: insc­-Gal4/+ UAS-dicer2",
    "ncbi_link": "cdk1: 34411
Gal4: 855828
pr-set7: 41743"
  },
  {
    "caption": "(A) Larval NSCs of control (ctrl; yw) and ebd1240 at 24h ALH were stained for Deadpan (Dpn) and Miranda (Mira). (B) Quantifications of cellular extensions for genotypes in (A). Control: n=886, 11 BL; ebd1240: n=864, 12 BL. (C) Larval brains of control (ctrl; yw) and ebd1240 at 24h ALH were labelled with Dpn and EdU. (D) Quantifications of NSC without EdU incorporation for genotypes in (C). Control: n=1034, 12 BL; ebd1240: n=1139, 16 BL. Data information: Data are presented in (B, D as mean ± SD. n numbers in (B, D, were total NSCs counted with total brain lobes measured, while each brain lobe was considered as one biological replicate. Statistical analyses were done comparing two different genotypes using Mann-Whitney test (B, D ns: non-significant; *P < 0.05; ***P < 0.001.",
    "ncbi_link": "ebd1: 38082"
  },
  {
    "caption": "(H) Larval brains of control (ctrl; yw), ebd1-Flag overexpression under insc­-Gal4, pr-set7716/Df(3R)ED5644 (716/Df) and pr-set7716/Df with ebd1 induced with insc-Gal4 at 24h ALH were labelled with Dpn and EdU. (I) Quantifications of NSCs without EdU incorporation for larval brains in (H). Control: n=1162, 13 BL; insc>ebd1: n=997, 11 BL; pr-set7716/Df: n=928, 13 BL and pr-set7716/Df with ebd1 induced with insc-Gal4: n=1284, 16 BL. Data information: Data are presented in I) as mean ± SD. n numbers in I) were total NSCs counted with total brain lobes measured, while each brain lobe was considered as one biological replicate. Statistical analyses were done comparing among different genotypes using ordinary one-way ANOVA I). ns: non-significant; *P < 0.05; ***P < 0.001.",
    "ncbi_link": "ebd1: 38082
Gal4: 855828
pr-set7: 41743"
  },
  {
    "caption": "(A) Larval NSCs of control (ctrl; yw) and cdk1B47 at 24h ALH were labelled for Earthbound1 (Ebd1), Deadpan (Dpn), and Miranda (Mira). (B) Quantifications of the corrected total cell fluorescence (CCF) of Ebd1 in genotypes in (A). CCF = Integrated Density - (Area of selected cell × Mean fluorescence of background readings). CCFs were 846.9±394.2 for control (ctrl; yw; n=167, 14 BL) and 354.3±245.3 for cdk1B47 (n=211, 13 BL). (C, D) Larval NSCs of control (UAS-dicer2) and UAS-cdk1-Myc induced with insc-Gal4 at 6h ALH were labelled for Ebd1, Dpn, and Mira. (D) Quantifications of the CCF of Ebd1 in genotypes in (C). CCFs were 111.3±80.2 for control (n=157, 12 BL) and 346.6±221.1 for cdk1-Myc (n=181, 12 BL). Data information: Data are presented in (B, D, as mean ± SD. n numbers in (B, D, were total NSCs counted with total brain lobes measured, while each NSC was considered as one biological replicate. White arrows point to NSCs (A, C, Yellow dotted boxes indicate the region of zoomed-in images (A, C, Statistical analyses were done comparing between two different genotypes using Mann-Whitney test (B, D) Scale bars, 15 μm (A, C,",
    "ncbi_link": "cdk1: 34411
Gal4: 855828"
  },
  {
    "caption": "(E) qPCR analysis of cdk1 in larval brains of control (ctrl; yw) and ebd1240 at 24h ALH. n=3 as biological replicates. Statistical analyses were done comparing control (GAPDH1, GAPDH2, Tbp1 and Rpl32) and ebd1240, using two-tailed Student's t-test. The mRNA levels of control were normalized to 1. Data information: Statistical analyses were done comparing between two different genotypes using two-tailed Student's t-test (E).",
    "ncbi_link": "GAPDH1: 
GAPDH2: 
Rpl32: 
Tbp1: 
cdk1: 34411
ebd1: 38082"
  },
  {
    "caption": "Larval NSCs of control (ctrl; yw), ebd1240 and pr-set7716/Df(3R)ED5644 (716/Df) at 24h ALH were stained for Senseless (Sens), Dpn and Mira. (F) Data information: White arrows point to NSCs F). Yellow dotted boxes indicate the region of zoomed-in images F). Scale bars, 15 μm F).",
    "ncbi_link": "ebd1: 38082
pr-set7: 41743"
  },
  {
    "caption": "(A) Real-time quantitative PCR of the indicated genes (M1-like and M2-like macrophages markers) of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) compared with vehicle after normalization for housekeeping gene TBP (n=3 tumors), (*P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle (PLX4720: m-Arg1 P = 5.65E-06) (bevacizumab: m-Ccl5 P = 0.025) (COMBO: m-Ccl5 P = 0.0070; m-Cd40 P = 0.00099; m-Cxcl10 P = 0.043; m-Cxcl9 P = 0.046; m-Il1b P = 0.0367; m-Stat1 P = 0.049; m-Tlr2 = 0.00182; m-Arg-1 P = 0.0013).",
    "ncbi_link": "TBP: 
Arg-1: 11846
Ccl5: 20304
Cd40: 21939
Cxcl10: 15945
Cxcl9: 17329
Il1b: 16176
Stat1: 20846
Tlr2: 24088"
  },
  {
    "caption": "(E) Quantitative Real-time PCR of h-TGFB1 and m-Tgfb1 of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) compared with vehicle after normalization for the housekeeping gene TBP (n=3 tumors), *P < 0.05 versus vehicle (P = 0.043).",
    "ncbi_link": "TBP: 
TGFB1: 7040
Tgfb1: 21803"
  },
  {
    "caption": "(G) Real-time quantitative PCR of h-TGFB1 of A375 xenograft treated with PLX4720, bevacizumab or COMBO. Data are presented as expression fold change (log2) of relapsing tumors compared to responder tumors after normalization for housekeeping gene TBP (n=3 tumors) ***P < 0.001 versus vehicle (P = 0.0006).",
    "ncbi_link": "TBP: 
TGFB1: 7040"
  },
  {
    "caption": "I,J.  Luciferase activity controlled by the upstream 5'UTR fragment from Sox2  (WT and mutant), Rps21  (WT and mutant) and Actb. Treatments were applied for 12h. Data is normalized to vehicle and is represented as mean ± SD. n = 6 biological replicates. Two-way ANOVA with Tukey's multiple comparisons test (p-value specified). Data information: p ≡ p-value.",
    "ncbi_link": "Rps21: 66481
Sox2: 20674"
  },
  {
    "caption": "B. vSVZ  niche FACS  quantifications of total NSCs  (Total NSCs) & immunofluorescence  quantification of aNSCs   (Fraction of aNSCs) in WT or IFNAGR  KO mice  at 2, 7 and 22 months old (MO). Data from individual mice  is plotted. Inferred dynamics are depicted as a blue (WT) or red (IFNAGR  KO) line over time. Sample sizes: WT total at 60 days: 8 mice, WT total at 210 days: 3 mice, WT total at 660 days: 3 mice, WT fraction aNSCs   at 60 days: 3 mice, WT fraction aNSCs    at 660 days: 4 mice, IFNAGRKO total at 60 days: 8 mice, IFNAGRKO total at 180 days: 3 mice,  IFNAGRKO total at 660 days: 3 mice,  IFNAGRKO fraction aNSCs   at 60 days: 3 mice, IFNAGRKO fraction aNSCs   at 660 days: 3 mice.",
    "ncbi_link": "IFNAGR: 15975///15979"
  },
  {
    "caption": "Cells were infected with HIV-1 R5 Vpr-Blam for 4h or 48h and then incubated with CCF2 for 5 h at 11°C to prevent particle fusion during the staining process. For the indicated sample, T20 was added at the moment of infection. (E) Percentage of positive cells for the presence of the CFF2 product at 4h p.i. ** p<0.01calculated with 2way ANOVA test.",
    "ncbi_link": "Blam: 
Vpr: 155807"
  },
  {
    "caption": "Cells were infected with HIV-1 R5 Vpr-Blam for 4h or 48h and then incubated with CCF2 for 5 h at 11°C to prevent particle fusion during the staining process. For the indicated sample, T20 was added at the moment of infection. (F-G) Percentage of positive cells for the presence of the CFF2 product at 4h p.i. (left) and 48h p.i. (right) *p<0.05 calculated with 2way ANOVA test. The graphs show mean values +/- SD for cells from five and three donors, respectively.",
    "ncbi_link": "Blam: 
Vpr: 155807"
  },
  {
    "caption": "iDCs were spin-transduced with VLPs carrying Vpxmac239 one day prior to infection. Cells were incubated with anti-DC-SIGN and anti-MMR blocking antibody or isotype control for 30 min, infected with HIV-1 R5 Vpr-Blam for 4 hours to asses fusion or for 48 hours to asses productive infection. (I) Percentage of positive cells for the presence of the CFF2 product at 4 hours p.i. (J) Percentage of p24+ cells at 48 hours p.i. The graphs show mean values +/- SD for cells from three donors. *p<0.05 calculated with 2way ANOVA test.",
    "ncbi_link": "Blam: 
Vpr: 155807
Vpx: 1490006"
  },
  {
    "caption": "(H) iDC differentiated from peripheral blood monocytes for five days were spin-transduced with VLPs carrying Vpxmac239. One day later, iDCs were infected with HIV-1 R5 and cultured in 2D suspension, 2D collagen or 3D collagen. Productive infection was analyzed by p24 intracellular staining and FACS at 4 (d.p.i). The graph depicts mean values for cells from two donors.",
    "ncbi_link": "Vpx: 1490006"
  },
  {
    "caption": "(A) miR-515-5p expression increases the area of the tubulin cytoskeleton. Tubulin (green) and cell nucleus (blue). Objective x20. Bar: 200 µm.",
    "ncbi_link": "miR-515-5p: 574465///574462"
  },
  {
    "caption": "(B-C) miR-515-5p inhibits random (B) and directed (C) cell migration. The indicated cell lines were transfected with miR-515-5p for 48 h before time-lapse imaging was performed for 18 h (A) or transwell migration assays were performed for 9 h (C). (B-left panel) Plots show overlays of representative trajectories travelled. (B-right panel) The distance of migration was quantified and represented as the mean ± SEM of values normalised to the respective control condition. (C-left panel) Representative field of view from the bottom of the transwell chambers. Scale bar is 20 µm. (C-right panel) Data represent percentage of the average number migratory cells per field (n=5 fields per condition). Data are mean of three experiments ± SEM. (B-C) P values were calculated by t-test between miRNA (515-5p) values and their respective non-targeting control miR (NC) values (***, P<0.001). All data shown are representative of experiments performed at least in triplicate.",
    "ncbi_link": "miR-515-5p: 574465///574462"
  },
  {
    "caption": "(A) RNA-seq of MCF7 and MDA-MB-231 transfected with miR-515-5p revealed the down-regulation of five transcripts, NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4.",
    "ncbi_link": "CDC42BPA: 8476
FZD4: 8322
MARK4: 57787
miR-515-5p: 574462///574465
NRAS: 4893
PIK3C2B: 5287"
  },
  {
    "caption": "(B-D) The effect of miR-515-5p overexpression on NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNA levels in MCF7 (B), MDA-MB-231(C), A549 and H1299 (D) was determined by qPCR 48 h following transfection of the indicated cell line with non-targeting control miR (NC) or miR-515-5p. Data is displayed as the normalised mean ± SEM. P values were calculated by t-test between miRNA conditions and their respective NC conditions (*, P<0.05; **, P<0.01; ***, P<0.001).",
    "ncbi_link": "CDC42BPA: 8476
FZD4: 8322
MARK4: 57787
miR-515-5p: 574462///574465
NRAS: 4893
PIK3C2B: 5287"
  },
  {
    "caption": "(E-F) miR-515-5p directly interacts with NRAS, MARK4 and PI3KC2B's 3'UTR. Relative luciferase activity levels were measured 24 h after co-transfection of MCF-7 (E) and MDA-MB-231 (F) with 3'UTR-luciferase reporter constructs and either with miR-515-5p or miR NC. Data shown are normalised mean of three independent experiments ± SEM. (B-F) P values were calculated by t-test between miRNA conditions and their respective NC conditions (*, P<0.05; **, P<0.01; ***, P<0.001).",
    "ncbi_link": "luciferase: 
MARK4: 57787
miR-515-5p: 574465///574462
NRAS: 4893
PI3KC2B: 5287"
  },
  {
    "caption": "MARK4 siRNA-mediated silencing increases the tubulin cytoskeletal area (A). (A) Data shown are representative of experiments performed in triplicate. Bar graph represents the average ± SEM of n ≥ 50 per technical replicate with 3 technical replicates per conditions.",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "MARK4 siRNA-mediated silencing reduces random (B) migration in MDA-MB-231 (MDA), A549 and H1299 cells.Cells were transfected either with siRNA targeting MARK4 (M4) or a non-targeting control (NC) for 48 h before time-lapse imaging was performed for 18 h (B). (B-top panel) Plots show overlays of representative trajectories described. (B-bottom panel) The migration distance was quantified and represented as the normalised mean ± SEM. (C-top panel) Representative field of view from the bottom side of the transwell membrane. (C-bottom panel) Graphs indicate cell migration expressed as a percentage of the average of migratory cells per field (n=5 fields per condition). (B-C) Data are mean of three experiments ± SEM. (A-C) P values were calculated by t-test between the siRNA-transfected and the respective control condition (***P<0.001).",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "MARK4 siRNA-mediated silencing reduces directed (C) migration in MDA-MB-231 (MDA), A549 and H1299 cells.(C-top panel). Cells were transfected either with siRNA targeting MARK4 (M4) or a non-targeting control (NC) for 48 h before transwell assay for 9h (C). Representative field of view from the bottom side of the transwell membrane. (C-bottom panel) Graphs indicate cell migration expressed as a percentage of the average of migratory cells per field (n=5 fields per condition). (B-C) Data are mean of three experiments ± SEM. (A-C) P values were calculated by t-test between the siRNA-transfected and the respective control condition (***P<0.001).",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "(A-B) The indicated cell lines were transfected with either miR-515-5p or a non-targeting miR (miR NC) together with a MARK4 expressing or an empty vector (EV) plasmid DNA. MARK4 over-expression rescues the inhibition by miR-515-5p of random (A) and directed (B) migration of the indicated cell lines. (A-left panel) Plots show overlays of representative trajectories described for MDA-MB-231 cells (n=30). (A-right panel) The migration distance was quantified and represented as the normalised mean ± SEM. (B-left panel) Representative field of view from the bottom side of the transwell membrane for MDA-MB-231. (B-right panel) Graphs indicate cell migration expressed as a percentage of the average of migratory cells per field (n=5 fields per condition). Data are mean of three experiments ± SEM. (A-C) P values were calculated by t-test between the transfected and the respective control condition (EV+miR-NC) (*,P<0.05; **,P<0.01; ***,P<0.001).",
    "ncbi_link": "MARK4: 57787
miR-515-5p: 574462///574465
miR-515-5p: 574465///574462"
  },
  {
    "caption": "(A-B) Overall survival of ER-negative metastatic breast cancer (n=226) (A) and lung adenocarcinoma (n=719) (B) patients according to MARK4 mRNA levels found in their tumors was represented using the Kaplan Meier-plotter [25].",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "(C) A cDNA array for 24 matched lung cancers and surrounding normal tissue was analysed for MARK4 expression. Expression levels from tumors were normalised to their respective normal control and the percentage of cases for the indicated fold expression in the tumor represented as a pie-chart.",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "(D-F) MARK4 protein expression was determined by histoimmunochemistry in (D-E) a tissue microarray comprising 90 lung tumor and 10 normal lung samples or (F) a home-made tissue microarray comprising 100 matched cases of primary and metastatic tumors. (D-E) The percentage of positivity for MARK4 staining in lung tumors versus normal lung samples (D) or in lung tumors according to their histological subtypes (E) is represented. (F) The percentage of cases with increased, decreased or unchanged levels of MARK4 in metastatic lesions as compared to the corresponding primary tumors is represented.",
    "ncbi_link": "MARK4: 57787"
  },
  {
    "caption": "(A-D) Low expression of miR-515-5p is linked to survival in both Lung and Breast cancer. (A) Survival analysis of miR-515-5p from 195 lung adenocarcinoma samples from the TCGA. (B) Survival analysis of miR-515-p from 34 lung squamous cell carcinoma from the TCGA. (C) Survival analysis of miR-515-5p from 60 Breast cancer samples from the Lyng Ditzel Breast Study (GSE37405). (D) Survival analysis of miR-515-5p from 33 Breast cancer from the GSE7405 Breast study. Analysis and plot were obtained with SurvMicro http://bioinformatica.mty.itesm.mx:8080/Biomatec/Survmicro.jsp for (A-C) and with MIRUMIR for (D).",
    "ncbi_link": "miR-515-5p: 574465///574462
miR-515-p: 574465///574462"
  },
  {
    "caption": "(E) Comparison of miR-515-5p expression in 18 primary and matched metastatic lesions from breast cancer patients. miR-515-5p levels were quantified by TaqMan qRT-PCR. Absolute values were normalized to u6 snRNA values and displayed as a dot-plot. Bar; Mean, Whiskers; SEM.",
    "ncbi_link": "u6: 
miR-515-5p: 574465///574462"
  },
  {
    "caption": "(F) MDA-MB-231 cells were inoculated into the mammary fat pads of nude mice and allowed to form metastatic deposits [22]. miR-515-5p and MARK4 levels were then determined in the primary and indicated secondary lesions. Data are average ± SEM of technical triplicates.",
    "ncbi_link": "MARK4: 57787
miR-515-5p: 574465///574462"
  },
  {
    "caption": "(G) Luciferase-expressing A549 cells overexpressing miR-515-5p or a non-targeting control (miR-NC) were injected in the tail-vein of SCID mice and the development of tumor burden monitored by whole animal-imaging in response to luciferin administration at week 1 and 4 following injection. (G-left panel) Representative imaging of the same animals for the indicated conditions at week 1 and 4. (G-Right panel) The emitted photons were quantified and the signals normalised to the corresponding readings at week 1. Data represented are representative of three independent experiments. (E-G) P values were calculated by t-test (*, P<0.05; **, P<0.01; ***, P<0.001).",
    "ncbi_link": "Luciferase: 
miR-515-5p: 574465///574462"
  },
  {
    "caption": "A549-Luc cells transfected either with miR-515-5p precursor (miR), siRNAs to MARK4 (siMARK4) or the corresponding control sequences (C and NT, respectively) were injected in Scid mice through the tail vein. 4 weeks later, the mice were sacrificed, their lungs extracted and fixed prior to staining for Luciferase expression. (A) Representative pictures showing the presence of A549-Luc cells in the lungs of NT mice either as single cells (upper panel) or as a tumour mass (lower panel). (B) Percentage of the area covered by tumour cells on randomly observed fields of views. Quantification was performed using Photoshop CS4. Each spot corresponds to quantification of an individual 1 mm x 1.5 mm field. Transversal bar; Median. Statistics: Student t-test. *, p≤0.05.",
    "ncbi_link": "Luc: 
Luciferase: 
MARK4: 57787
miR-515-5p: 574465///574462"
  },
  {
    "caption": "Single-cell RNA sequencing was performed to profile cell populations in normal mouse pancreas (n = 2), early KIC (40-day-old, n = 2) and late KIC (60-day-old, n = 3) pancreata. Samples from the same stage were pooled. Violin plots of expression of Il6, Tgfbr1 and Tgfbr2 in distinct cell populations is shown.",
    "ncbi_link": "Il6: 16193
Tgfbr1: 21812
Tgfbr2: 21813"
  },
  {
    "caption": "Pearson and Spearman correlation of the expression of IL6 and TGFBR2 in PDA patients from TCGA (n = 223) using R.",
    "ncbi_link": "IL6: 3569
TGFBR2: 7048"
  },
  {
    "caption": "CAF-PC2 cells were treated with TGFβ (30 ng/ml) for 24 hours with siRNA-mediated knockdown of JUNB, JUND, SMAD4 or RELA. CM was collected and subjected to human IL-6 ELISA.",
    "ncbi_link": "JUNB: 3726
JUND: 3727
RELA: 5970
SMAD4: 4089"
  },
  {
    "caption": "CAF-PC2 cells were treated with IL-1α (1 ng/ml) (H) for 24 hours with siRNA-mediated knockdown of JUNB, JUND, SMAD4 or RELA. M was collected and subjected to human IL-6 ELISA.",
    "ncbi_link": "JUNB: 3726
JUND: 3727
RELA: 5970
SMAD4: 4089"
  },
  {
    "caption": "Overall survival of PDA patients from TCGA with and without TGFBR2 mutation.",
    "ncbi_link": "TGFBR2: 7048"
  },
  {
    "caption": "Loss-of-function mutation of Tgfbr2 was generated by CRISPR with two different gRNAs (mut1 and mut2) in the mouse PDA cell line BMFA3 derived from KPfC model. Control cell line (Tgfbr2wt) and two Tgfbr2-mutant cell lines (Tgfbr2mut1 and Tgfbr2mut2) were treated with TGFβ (30 ng/ml) for 5 hours. Cell lysates were harvested and western blotting for P-SMAD2, SMAD2, SMAD4, P-ERK1/2, ERK1/2, P-P38, P38, and actin was performed.",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Immunofluorescence was performed to study the expression and localization of E-cadherin and SMAD4 after TGFβ treatment (30 ng/ml for 24 hours) in control cell line and two Tgfbr2-mutant cell lines. Scale bars = 50 μm (fluorescent), scale bars = 100 μm (brightfield).",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Control cell line (Tgfbr2wt) (A) and two Tgfbr2-mutant cell lines (Tgfbr2mut1 and Tgfbr2mut2) (B-C) were treated with TGFβ at different time points, and cell growth (MTT) assays were performed. P value by t test is shown. NS, not significant.",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Subcutaneous tumors established from control cell line (D) and two Tgfbr2-mutant cell lines (E-F) in C57Bl/6 mice received rat IgG Mac48 (control) or 2G8 (each 30 mg/kg 2x/week, n = 4/group). Therapy started at day 12 post tumor cell injection; mice were on therapy for 16 days. Tumor volume was measured twice per week. P values by t test are shown.",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Control cell line (Tgfbr2wt; G&I) and the Tgfbr2-mutant cell line (Tgfbr2mut1; H&J) were orthotopically implanted in C57Bl/6 mice. Mice received rat IgG Mac48 or 2G8, n = 9-10/group for survival study (each 30 mg/kg 2x/week).",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Control cell line (Tgfbr2wt; G&I) and the Tgfbr2-mutant cell line (Tgfbr2mut1; H&J) were orthotopically implanted in C57Bl/6 mice. Mice were sacrificed when they became moribund. Tumors were harvested and weighed (K-L).",
    "ncbi_link": "Tgfbr2: 21813"
  },
  {
    "caption": "Control shRNA or two different shRNAs against IL6RA were used to knock down IL6RA in the Tgfbr2-mutant cell line Tgfbr2mut1. Cell lysates were harvested and western blotting for IL6RA and tubulin.",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "3D culture: control or IL6RA knockdown Tgfbr2mut1 cells were seeded on poly-HEMA-coated 96-well plates and cultured for 4 days (5000 cancer cells for monoculture, 3000 cancer cells + 2000 NIH 3T3 for co-culture).",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "3D culture: control or IL6RA knockdown Tgfbr2mut1 cells were seeded on poly-HEMA-coated 96-well plates and cultured for 4 days (5000 cancer cells for monoculture, 3000 cancer cells + 2000 NIH 3T3 for co-culture). Control IgG, 2G8 and IL-6 neutralizing antibody (each 100 ng/ml, n = 5/group). Scale bars = 50 μm. P values by t test are shown (C).",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "Subcutaneous tumors established from control and IL6RA knockdown Tgfbr2-mutant cell lines in C57Bl/6 mice received rat IgG Mac48 (control), 2G8 or anti-mouse IL-6 antibody MP5-20F3 (each 30 mg/kg 2x/week, n = 5/group). For NK cell depletion, prior to therapies, mice received 50 μg of control rabbit IgG or anti-Asialo-GM1 three days in a row. For maintenance, 25 μg of control rabbit IgG or anti-Asialo-GM1 were given 2X/week throughout the whole study. Therapy started at day 12 post tumor cell injection and mice were on therapy for 16 days. Tumor volume was measured twice per week. P values by t test are indicated.",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "Subcutaneous tumors established from control and IL6RA knockdown Tgfbr2-mutant cell lines in C57Bl/6 mice received rat IgG Mac48 (control), 2G8 or anti-mouse IL-6 antibody MP5-20F3 (each 30 mg/kg 2x/week, n = 5/group). For NK cell depletion, prior to therapies, mice received 50 μg of control rabbit IgG or anti-Asialo-GM1 three days in a row. For maintenance, 25 μg of control rabbit IgG or anti-Asialo-GM1 were given 2X/week throughout the whole study. Therapy started at day 12 post tumor cell injection and mice were on therapy for 16 days. Tumor volume was measured twice per week. P values by t test are indicated.",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "Subcutaneous tumors established from control and IL6RA knockdown Tgfbr2-mutant cell lines in C57Bl/6 mice received rat IgG Mac48 (control), 2G8 or anti-mouse IL-6 antibody MP5-20F3 (each 30 mg/kg 2x/week, n = 5/group). For NK cell depletion, prior to therapies, mice received 50 μg of control rabbit IgG or anti-Asialo-GM1 three days in a row. For maintenance, 25 μg of control rabbit IgG or anti-Asialo-GM1 were given 2X/week throughout the whole study. Therapy started at day 12 post tumor cell injection and mice were on therapy for 16 days. Tumor volume was measured twice per week. P values by t test are indicated.",
    "ncbi_link": "IL6RA: 16194
Tgfbr2: 21813"
  },
  {
    "caption": "(A) NSCLC expressing single site mutants of EGFR, PC9 (3X106) or H3255 (8X106), were seeded in 10-cm dishes. On the next day, complete media were replaced with media containing serum (1%) and the cells were treated for 24 hours with different EGFR-specific TKIs (erlotinib, 50 nM; osimertinib, 50 nM, or afatinib, 10 nM), either alone or in combination with 2XmAbs (cetuximab and trastuzumab, 5 μg/ml each). Thereafter, cells were washed with cold saline and extracted. Proteins were separated using gel electrophoresis and transferred onto nitrocellulose membranes. After blocking, membranes were incubated overnight with the indicated primary antibodies, followed by incubation with horseradish peroxidase-conjugated secondary antibodies (60 minutes), and treatment with Clarity™ Western ECL Blotting Substrates (Bio-Rad). ECL signals were detected using the ChemiDoc™ Imaging System (Bio-Rad) and images were acquired using the ImageLab software. Signals (relative to Control) were quantified and normalized to the signals of GAPDH (numbers shown below each lane).",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "PC9 cells (3X106/mouse) were subcutaneously implanted in the flanks of CD1-nu/nu mice. When tumors became palpable, mice were randomized in groups of 5-9 animals and treated for 90 days (grey areas) with 2XmAbs (cetuximab plus trastuzumab, 0.2 mg/mouse/injection), once every three days, or with erlotinib (50 mg/kg/day), once per day. Alternatively, mice were treated with combinations of erlotinib (50, 20, 10, 5 or 1 mg/kg) and the two monoclonal antibodies. Following 60 days of treatment reduced the frequency of erlotinib administration to once every other day (underneath dotted line). animal survival (B) are shown. Mice were euthanized when tumor size reached 1,500 mm3.",
    "ncbi_link": "CD1: 111334"
  },
  {
    "caption": "PC9 cells (exon 19 deletion) were subcutaneously implanted in the flank of CD1-nu/nu mice (3X106/mouse). When tumors became palpable, mice were randomized in groups of 5-9 animals and treated for 90 days (grey areas) with 2XmAbs (cetuximab plus trastuzumab, each at 0.1 mg/mouse/injection) once every three days, or daily with different TKIs: osimertinib (5 mg/kg), afatinib (5 mg/kg) or imatinib (100 mg/kg), either alone or in combination with the two antibodies. Following 60 days of treatment, the frequency of TKI administration was reduced to once every other day (underneath dotted lines), while mAb treatment remained unaltered. animal survival (B) are shown. Mice were euthanized when tumor size reached 1,500 mm3.",
    "ncbi_link": "CD1: 111334"
  },
  {
    "caption": "CD1-nu/nu mice carrying PC9 xenografts were divided in groups (2-3 mice/group) and treated for seven days with different TKIs: erlotinib (50 mg/kg or 20 mg/kg), osimertinib (5 mg/kg) or afatinib (5 mg/kg), either alone or in combination with 2XmAbs (cetuximab and trastuzumab, each at 0.1 mg/mouse/injection). when singly applied used erlotinib at 50 mg/kg. (B) After treatment, all mice were sacrificed and tumors extracted. Protein extracts were resolved by means of electrophoresis and transfer to nitrocellulose membranes, which were later incubated overnight with the indicated antibodies. This was followed by incubation with peroxidase-conjugated secondary antibodies. Signals were detected using ChemidocTM (from Bio-Rad), quantified and normalized to the signals of GAPDH or tubulin (numbers shown below each lane).",
    "ncbi_link": "CD1: 111334"
  },
  {
    "caption": "A, B PC9 cells (3X106/mouse) were subcutaneously injected in the flanks of CD1-nu/nu mice. When tumors reached a volume of approximately 500 mm3, mice were treated daily with erlotinib (50 mg/kg, blue area; panel A) or with osimertinib (5 mg/kg, grey area; panel B) using oral gavage. Initially, all tumors displayed stable disease or they regressed, but eventually all started relapsing. Once relapsing tumors reached 800 mm3, while under erlotinib or osimertinib treatment, we supplemented the treatment with a combination of 2XmAbs (cetuximab and trastuzumab, each at 0.1 mg/mouse/injection; twice a week) plus either erlotinib (50 mg/kg; A, red area) or osimertinib (5 mg/kg; B, orange area). Tumor volumes of individual mice are shown.",
    "ncbi_link": "CD1: 111334"
  },
  {
    "caption": "A, B NSG mice were pre-implanted with tumor fragments derived from two different PDX models: (A) TM00199 (L858R-EGFR; from The Jackson Laboratory) or (B) TM00193 (E746_A750 del-EGFR; from The Jackson Laboratory). Once tumors reached approximately 300 mm3, mice were treated with monoclonal antibodies (2XmAbs, cetuximab plus trastuzumab, 200μg/injection) twice a week, or with EGFR TKIs, erlotinib (50mg/kg) or osimertinib (10mg/kg) daily. Alternatively, mice were treated with a combination of 2XmAbs and either erlotinib or osimertinib, for either 32 days (A) or 42 days (B). Tumor growth was monitored twice a week. the antibodies were injected into the peritoneum and the TKIs were delivered orally. The figure shows tumor volumes of individual mice and the respective survival curves (right hand panels). The grey areas mark time windows of animal treatment.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "(B) For RNAseq analyses, PC9 cells (3X106/mouse) were subcutaneously injected in the flanks of 13 CD1-nu/nu mice. When tumors reached 500 mm3, mice were treated daily with erlotinib (50 mg/kg). Once tumors that initially responded to erlotinib monotherapy started relapsing and reached 800 mm3, we switched to a combination of 2XmAbs plus erlotinib (50 mg/kg). The respective tumor volumes were sacrificed when tumor volumes reached approximately 500 mm3 Mice responding to erlotinib (N=3) were sacrificed after one week of treatment Mice resistant to erlotinib (N=3) were sacrificed when tumor volumes reached 800 mm3 whereas mice responding to erlotinib+2XmAbs (N=2) were sacrificed after one week of treatment RNA was extracted from all 13 tumors and utilized for RNA-seq analysis. Differentially expressed (DE) genes in the Erlotinib (Er)+2XmAbs arm compared to the Control group are presented in the heatmap.",
    "ncbi_link": "CD1: 111334"
  },
  {
    "caption": "B Hops−/− mouse genotyping and protein expression. Genotyping by PCR using genomic DNA showed a 242bp band for wild type (Hops+/+) allele and a 331bp band for mutant (Hops−/−) allele. NTC is Null Template Control (left panel). Genotyping by real time PCR confirmed the absence of Hops mRNA in Hops−/− mice (middle panel). Protein extracts from Hops+/+ and Hops−/− MEFs were analysed by Western Blot using anti-HOPS antibody and anti-α-tubulin antibody as loading control (right panel). Data information: in B data are presented as mean ±SD.",
    "ncbi_link": "Hops: 64295"
  },
  {
    "caption": "C Offspring distribution. Different HOPS genotypes at weaning age (approximately postnatal day 21) from crosses between homozygous knockout mice males and heterozygous females (n=1525 pups). Data information: In C the χ2 test was performed to determine significant differences between the expected and observed ratios of Hops−/− to Hops+/− mice. P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "A Reduced caspase-3 activation in Hops−/− mice upon apoptotic stimulus. Hops+/+ and Hops−/− mice were treated with etoposide for the indicated times and thymus, spleen, testis and liver were harvested and Tissue-Tek® O.C.T. embedded. Sections were immunostained with anti-cleaved caspase-3 antibody followed by appropriate secondary antibody labelling (green). The graphs display the relative positive cells number. Scale bars, 10µm. Data information: all the experiments were performed three times in three different mice per condition and a representative example is shown. In A data are presented as mean ±SD. ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "Hops: 64295"
  },
  {
    "caption": "B HOPS affects p53 increase after stress in vivo. Whole-cell homogenates from organs, were immediately prepared and immunoblotted with antibodies to detect p53 and GAPDH. The p53 levels were semi-quantified using GAPDH as loading control and relative p53 levels at time 0 were assumed as 1. Data information: all the experiments were performed three times in three different mice per condition and a representative example is shown. In B data are presented as mean ±SD. ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "HOPS: 64295"
  },
  {
    "caption": "A Thymocytes from Hops+/+ and Hops−/− mice were treated with dexamethasone (Dex) and the apoptotic cells were measured by flow cytometry. The flow cytometry analysis plots are shown on the left and the data represented as a histogram on the right. Data information: the experiments were performed three times in primary cells from three different mice per condition. In A data are presented as mean ±SD. * P < 0.05; ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "Hops: 64295"
  },
  {
    "caption": "B HOPS was pivotal for apoptosis induction. Hops+/+ and Hops−/− MEFs were subjected to etoposide (Eto) and apoptosis was analysed by flow cytometry (left) and showed as a graph (right). Data information: the experiments were performed three times in primary cells from three different mice per condition. The experiments in MEFs were performed three times. Representative panels are shown. In data are presented as mean ±SD. * P < 0.05; ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "HOPS: 64295
Hops: 64295"
  },
  {
    "caption": "C HOPS overexpression in MEFs promotes apoptosis. Hops+/+ and Hops−/− MEFs were transiently transfected with an empty vector (pEGFP-N1) or with a Hops encoding vector (pEGFP-N1-Hops). The apoptotic cells were measured by flow cytometry (left) on the GFP positive and negative populations and showed as a graph (right). Data information: the experiments were performed three times in primary cells from three different mice per condition. The experiments in MEFs were performed three times. Representative panels are shown. In C data are presented as mean ±SD. * P < 0.05; ** P < 0.01; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "EGFP: 
Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "D HOPS affects p53 levels following stress in vitro. Hops+/+ and Hops−/− MEFs were treated with etoposide and harvested at the indicated time points. The p53 protein levels were semi-quantified using α-tubulin as loading control and relative p53 levels at 0 µM dosage were assumed as 1. Data information: the experiments were performed three times in primary cells from three different mice per condition. The experiments in MEFs were performed three times. Representative panels are shown.",
    "ncbi_link": "Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "A HOPS loss and p53 half-life. Hops+/+ and Hops−/− MEFs untransfected or transfected with HOPS, were analysed by immunoblotting following cycloheximide treatment for the indicated time (left panel). The p53 protein levels were semi-quantified using GAPDH as loading control and relative p53 levels at time 0 were assumed as 100% (right panel). Data information: all the experiments in MEFs were performed three times. Representative panels are shown. In A data are presented as mean ±SD.",
    "ncbi_link": "Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "B p19Arf-independent HOPS control of p53 half-life. p19Arf−/− MEFs untransfected (CTRL), transfected with empty vector (pSGV) or HOPS were treated with cycloheximide for the indicated times and subjected to immunoblot analysis with anti-p53, anti-HOPS and anti-GAPDH antibodies (left panel). The p53 protein levels were semi-quantified as above (right panel). Data information: all the experiments in MEFs were performed three times. Representative panels are shown. In B data are presented as mean ±SD.",
    "ncbi_link": "p19Arf: 12578
HOPS: 64295"
  },
  {
    "caption": "C HOPS and p53 ubiquitination. p53, HDM2, His-tagged ubiquitin were co-expressed in H1299 cells with HOPS or HOPS-G176A or HOPS-K126A mutants and treated with MG132. p53 ubiquitination rate was evaluated by elution using Ni2+-NTA His-bind resin followed by immunoblotting with anti-p53 and the indicated antibodies.",
    "ncbi_link": "His: 
HDM2: 4193
p53: 7157
HOPS: 71732"
  },
  {
    "caption": "D HOPS depletion and HOPS-G176A mutant affect p53 ubiquitination. Hops+/+ and Hops−/− MEFs untransfected and Hops−/− MEFs transfected with HOPS or HOPS-G176A mutant were co-expressed with p53, HDM2 and His-tagged ubiquitin. Cells were treated with MG132 and the ubiquitinated p53 fraction was recovered as above. Immunodetection of ubiquitinated p53 was performed using anti-p53 antibody and the samples were tested with the indicated antibodies. Data information: all the experiments in MEFs were performed three times. Representative panels are shown.",
    "ncbi_link": "His: 
HDM2: 4193
Hops: 64295
HOPS: 64295
p53: 7157"
  },
  {
    "caption": "E HOPS-G176A mutant ability to stabilize p53. Hops−/− MEFs were transfected with HOPS-G176A, subjected to cycloheximide treatment for the indicated times and analysed by immunoblotting using the indicated antibodies. Data information: all the experiments in MEFs were performed three times. Representative panels are shown.",
    "ncbi_link": "Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "E HOPS and p53 mitochondrial translocation in vivo. Hops+/+ and Hops−/− mice were treated with etoposide and thymus, spleen and testis were harvested. Organs were homogenized and mitochondrial fraction were isolated and analysed by immunoblotting versus p53. GAPDH and Tom20 are purity controls. p53 mitochondrial protein levels were semi-quantified using Tom20 as loading control and p53 levels at time 0 were assumed as 1. Data information: assays involving animals were performed three times in three different mice per condition. In E data are presented as mean ±SD. * P < 0.05; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "Hops: 64295"
  },
  {
    "caption": "F p53-dependent mitochondrial membrane potential (Δψm) induction in MEFs. Hops+/+ and Hops−/− MEFs were treated with etoposide and then incubated with JC-1 vital dye. The images were collected by fluorescent microscopy and representative images are shown (left panel). Scale bars, 10µm. Fluorescence was analysed by TECAN plate reader and plotted in the graph (right panel). Data information: assays involving animals were performed three times in three different mice per condition. Experiments on mitochondria from MEFs were performed five times. In F data are presented as mean ±SD. * P < 0.05; *** P < 0.001, by two tailed Student's t-test.",
    "ncbi_link": "Hops: 64295"
  },
  {
    "caption": "G p53 MOMP induction in HOPS deficiency. Mitochondria from Hops+/+ and Hops−/− MEFs, were purified and incubated with p53 recombinant protein. Cytochrome C release from mitochondria as metabolic marker was assayed by immunoblotting. Samples were tested to detect p53 as control and Tom20 as mitochondria structural marker. Data information: assays involving animals were performed three times in three different mice per condition. Experiments on mitochondria from MEFs were performed five times.",
    "ncbi_link": "Hops: 64295
HOPS: 64295"
  },
  {
    "caption": "A HOPS expression and p53 nuclear accumulation. HOPS was overexpressed in RKO and cells were fixed and stained with antibody against p53 (green). Nuclei were stained with DAPI (blue). Samples were analysed with fluorescent microscope and merged images are shown (right panel). Scale bars, 10µm. Cells were scored for p53 localization. The results are shown as percentage of nuclear versus cytoplasmic p53 localization in untransfected and HOPS transfected cells (left panel). Data information: all the experiments detailed above were performed three times, and representative panels are shown. In A data are presented as mean ±SD.",
    "ncbi_link": "HOPS: 83590"
  },
  {
    "caption": "B Biochemical analysis of HOPS intracellular localization. RKO cells were transfected or not with HOPS and fractionated into nuclear and cytoplasmic component. Aliquots relative to the same cell number per fraction were immunoblotted using anti-p53 and anti-HOPS antibodies. GAPDH and Lamin B1 are purity controls of cytoplasmic and nuclear fraction respectively. Data information: all the experiments detailed above were performed three times, and representative panels are shown.",
    "ncbi_link": "HOPS: 83590"
  },
  {
    "caption": "HOPS and p53 binding to importin α. Untransfected or HOPS transfected RKO cells were treated with etoposide and each sample was evaluated by immunoprecipitation with anti-p53 and analysed by immunoblotting using anti-importin α antibody. Arrowhead indicates the importin α specific signal. Data information: all the experiments detailed above were performed three times, and representative panels are shown.",
    "ncbi_link": "HOPS: 83590"
  },
  {
    "caption": "D PCAF-mediated p53 acetylation. p53 and PCAF Flag-tagged were co-expressed in H1299 cells with or without HOPS and treated with trichostatin A and nicotinamide. p53 acetylation levels were evaluated by immunoprecipitation with anti-p53 antibody followed by immunoblotting with anti-acetylated-Lysine (AcK), anti-p53, anti-Flag, anti-HOPS and anti-α-tubulin antibodies. Data information: all the experiments detailed above were performed three times, and representative panels are shown.",
    "ncbi_link": "Flag: 
PCAF: 8850
HOPS: 83590
p53: 7157"
  },
  {
    "caption": "B Heatmap of extracted CNA [log2 ratios] of STAT genes on chr17  (i.e., STAT3, STAT5A  and STAT5B), and other relevant tumor suppressors (i.e, STAT1, SOCS1  and TP53) and oncogenes (MYC). Red indicates gain/amplification, blue indicates loss/deletion. The balance threshold was set to +/- 0.1. P33 presented with two malignant clones in the blood  and both were sequenced (P33_1 (Clone 1), P33_2 (Clone 2)). *Tetraploid malignant clone.",
    "ncbi_link": "MYC: 4609
SOCS1: 8651
STAT1: 6772
STAT3: 6774
STAT5A: 6776
STAT5B: 6777
TP53: 7157"
  },
  {
    "caption": "A-C Spearman correlation analysis using CNA log2 ratios and the percentage of clonal CD3+ cells detected in patients  for (A) STAT3, (B) STAT5A and (C) STAT5B.",
    "ncbi_link": "STAT3: 6774
STAT5A: 6776
STAT5B: 6777"
  },
  {
    "caption": "D-F RT-qPCR expression data of (C) STAT3, (D) STAT5A, and (E) STAT5B  genes from whole PBMCs  isolated from patient blood  (n = 5) or healthy controls (n = 9). GAPDH  expression was used for normalization. Statistical significance was calculated using two-tailed unpaired t-test. P-value: <0.01 (**), <0.0001 (****). One experiment was performed in technical triplicates. The bold dashed line in the middle of the violin plot denotes the median value, while the thin dotted lines denote the interquartile range.",
    "ncbi_link": "GAPDH: 2597
STAT3: 6774
STAT5A: 6776
STAT5B: 6777"
  },
  {
    "caption": "A-C Graphic depicts the aberration patterns on (A) chromosome 17 (STAT3/5), (B) chromosome 2 (STAT1) and (C) chromosome 16 (SOCS1) in the CTCL  cell lines used in the study. Aberration patterns are represented as the log2 ratio of the fluorescence intensity of the tumor DNA vs. reference DNA and were generated by aCGH. Immunoblotting  for total protein STAT1/3/5 and activation levels: phospo-Tyr (701)-STAT1/phospho-Tyr (705)-STAT3/phospho-Tyr (694/699)-STAT5, and SOCS1 protein levels. The cytokine-dependent cell line, SeAx, was collected 30 min after 5 ng/ml  IL-2 and IL-4 cytokine addition. HSC70  was used as loading control. One representative out of three independent experiments is shown.",
    "ncbi_link": "SOCS1: 8651
STAT1: 6772
STAT3: 6774"
  },
  {
    "caption": "G Heatmap of IC50  values calculated from drug response analysis  using CellTiter-Blue  or CellTiter-Glo viability assays upon 48h drug treatment. One representative out of three independent experiments performed in triplicates is shown. Grey represents the presence of STAT3/5 gain.",
    "ncbi_link": "STAT3: 6774"
  },
  {
    "caption": "A Inhibitor treatment was carried out with increased dose escalation for 24h. SeAx  cells were collected 2h after 7,5 ng/ml IL-2 and  IL-4 cytokine addition. STAT3/5 target gene products MYC, PIM1,  MCL-1, and AKT1/2/3, as well as proteins regulating the cell cycle, such as CYCLIN D2 and D3, and CDK6  were probed by Western blotting. HSC70  served as loading control. The normalized protein levels, quantified by densitometry, are shown below the respective blots. One representative out of three independent experiments is shown.",
    "ncbi_link": "STAT3: 6774"
  },
  {
    "caption": "E Heatmap showing the IC50  values upon treatment of primary PBMCs  isolated from L-CTCL patients  with JPX-0750, IQDMA  and FRAx597. One experiment performed in triplicates using CellTiter-Glo viability assays  upon 48h drug treatment is shown. The relative STAT3/5 log2 ratio value is depicted in grey.",
    "ncbi_link": "STAT3: 6774"
  },
  {
    "caption": "(C) Immunolocalization of CDKA;1 (green) and ASY1 (red) on spread chromsomes in leptotene and zygotene of wild-type plants expressing a functional PROCDKA;1:CDKA;1:Strep construct. The last lane shows a magnification of the region marked by the red rectangle. Arrowheads indicate synapsed regions of homologous chromosomes where CDKA;1 is no longer present. Scale bar: 5 μm.",
    "ncbi_link": "Strep: 
CDKA;1: 824036"
  },
  {
    "caption": "(D) Chromosome spread analysis of the wildtype and the hypomorphic cdka;1 mutant CDKA;1T161D. (a, h) zygotene or zygotene-like stages; (b, i) pachytene or pachytene-like stages; (c, j, k) diakinesis or dikinesis-like stages; (d) metaphase I; (e, i, m, n) end of meiosis I with two (e, m) or three (i) pools of chromosomes; (f) metaphase II; (g) tetrad. Red arrowheads indicate the initiated formation of a phragmoplast. White arrowheads depict mitochondria. Scale bars: 10 μm.",
    "ncbi_link": "cdka;1: 824036
CDKA;1: 824036"
  },
  {
    "caption": "(A) ASY1:GFP and ASY1T142D:GFP localization in late G2 and leptotene of male meiocytes of the wildtype and CDKA;1T161D mutants. ASY3:RFP, highlighting chromsomes, was used as a marker for the staging of meiosis. Scale bar: 5 μm.",
    "ncbi_link": "CDKA;1: 824036"
  },
  {
    "caption": "(B) Localization patterns of different ASY1:GFP variants together with ASY3:RFP (for staging of zygotene and pachytene) in a asy1 mutant background during prophase I. Bar: 5 μ",
    "ncbi_link": "GFP: 
asy1: 843058
ASY1: 843058"
  },
  {
    "caption": "(C) Signal distribution profiles of ASY1:GFP and ASY1T142V:GFP at leptotene The many small peaks with low amplitude in ASY1T142V:GFP indicate diffused localization as opposed to the clear peaks seen in the wildtype.",
    "ncbi_link": "ASY1: 843058"
  },
  {
    "caption": "(D, E) Immunolocalization of ASY1 (D) and ZYP1 (E) in ASY1:GFP (asy1) and ASY1T142V:GFP (asy1) plants using anti-GFP and anti-ZYP1 antibodies, respectively. DNA was stained with DAPI (blue). Scale bars: 5 μm.",
    "ncbi_link": "GFP: 
asy1: 843058
ASY1: 843058"
  },
  {
    "caption": "(A) Localization patterns of ASY1T142V;T184V:GFP together with ASY3-RFP in the wildtype and pch2 mutants. Please note that images of ASY1T142V;T184V:GFP in pch2 mutants were taken with increased sensitivity for a better visibility. Scale bar: 5 μm.",
    "ncbi_link": "pch2: 828573"
  },
  {
    "caption": "(B) Seed sets (mean ± SD, n = 5) of WT, asy1, pch2, asy1 pch2, ASY1T142V;T184V:GFP (asy1) and ASY1T142V;T184V:GFP (asy1 pch2) plants. Asteriks indicate significant differences (two-tailed t-test, P < 0.01) and ns depicts no significant difference. Scale bar: 2 mm.",
    "ncbi_link": "GFP: 
asy1: 843058
ASY1: 843058
pch2: 828573"
  },
  {
    "caption": "(C) Localization patterns of ASY1:GFP, ASY1T142V;T184V:GFP, and ASY11-570:GFP in the wildtype (WT) and/or in pch2 mutant plants at early prophase I. Scale bars: 5 μm.",
    "ncbi_link": "pch2: 828573"
  },
  {
    "caption": "A WT and Ccnc-/- MEF cultures were treated with 0.4 mM H2O2 as indicated, extracts prepared and immunoprecipitated with antibody recognizing the active conformation of Bax. The immunoprecipitates were subjected to Western blot analysis and probed for total Bax or cyclin C. Whole cell extracts (WCE) were subjected to Western blot analysis as indicated to control for protein concentrations in the extracts. Molecular weight markers (kDa) are indicated on the left.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "F Drp1 is required for cyclin C-Bax interaction. Extracts were prepared from wild type or Drp1-/- MEF cultures treated or not with H2O2 and analyzed for the presence of Bax and cyclin C as described in A. Molecular weight markers (kDa) are indicated on the left.",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": "B Timecourse experiment with wild type and Ccnc-/- MEF cells treated with S-HAD (10 µM) for the times indicated (n=3). Error bars indicate SD. Asterisks indicate p values <0.05 from pretreatment control (Student's T-Test).",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "MEF cells were fixed before (control) and following S-HAD treatment (10 µM, 4 h) then nuclei (DAPI), cyclin C (indirect immunofluorescence) and mitochondria (MitoTracker Red) were visualized by fluorescence microscopy. Merge panels present DAPI staining (blue) only. S-HAD peptide activity requires cyclin C. The experiment described in A was repeated with Ccnc-/- MEF cultures.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "C Wild type and Ccnc-/- MEF cultures were treated with S-HAD and cisplatin (CP) as just described. Cells were imaged and examined for a \"rounding up\" phenotype diagnostic for death.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "D Cyclin C is required for normal Bax oligomerization in response to cisplatin. Whole cell extracts prepared from DSP crosslinked wild type and CCNC-/- MEF cells exposed to cisplatin (30 µM, 16 h) were probed for total Bax. Bax multimers are indicated. Molecular weight markers (kDa) are indicated on the left.",
    "ncbi_link": "CCNC: 51813
Cyclin C: 51813"
  },
  {
    "caption": "A S-HAD treatment induces mitochondrial ROS. Wild type and Ccnc-/- MEF cultures were treated with S-HAD (10 µM, 24 h), rotenone or vehicle control as indicated. Mitochondrial ROS was measured by MitoSox staining (4 µM, 15 min) and quantitative confocal imaging. Error bars indicate SD. n=3, asterisk indicates p<0.05 (Student's T-test), n.s., not significantly different.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "B Quenching mitochondrial ROS reduces cyclin C-Bax interaction. Wild type and Ccnc-/- MEF cultures were treated with S-HAD (10 µM, 16 h) and 100 nM mitochondrial-specific reactive oxygen scavenger MitoTempol. Western blot analysis was conducted as described in Fig. 1. Molecular weight markers (kDa) are indicated on the left.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "C Insulin treatment stimulates S-HAD induced Bax activation. Wild type and Ccnc-/- MEF cultures were grown with or without insulin (10 µg/ml) then treated with S-HAD (10 µM, 2 h). Mitochondrial and cytosolic fractions were prepared and probed for the indicated proteins. Atp5A and ß-actin levels control for mitochondrial and cytosolic loading, respectively. The two blots were prepared, processed and developed identically. Molecular weight markers (kDa) are indicated on the left.",
    "ncbi_link": "Ccnc: 51813"
  },
  {
    "caption": "C) MXE saturation analysis. Whereas increasing amounts of RNA-seq reads should lead to the confirmation of further MXE candidates, more RNA-seq reads might also result in the rejection of previously validated MXEs. The green curves show the number of validated MXEs in relation to the percentage of total RNA-seq reads used for validation. The orange curves indicate the number of initially 'validated MXEs' that were rejected with increasing amounts of reads. Grey dashed lines indicate the point of saturation, which is defined as the point where a two-fold increase in reads leads to rejection of less than 1% of the validated MXEs. Of note, whereas the rejection of validated MXEs saturates with 20% of the data the amount of novel MXE validations is still rapidly increasing.",
    "ncbi_link": "MXE: 
MXEs: "
  },
  {
    "caption": "E) Size and distribution of multi-cluster MXEs.",
    "ncbi_link": "MXEs: "
  },
  {
    "caption": "A) Heatmap showing all differentially expressed MXE clusters with at least 3 RPKM. Here, we used the Gini coefficient, which is a measure of the inequality among values of a frequency distribution (Ceriani & Verme, 2012) and has successfully been used to determine tissue-enriched gene sets (Zhang et al, 2017), to determine highly tissue-specific MXEs (maximum normalized Gini index of cluster) and MXEs with a broad tissue expression distribution (minimum Gini index). For each MXE cluster the percent-spliced-in (PSI) value of the ubiquitous MXE (minimum Gini index) is subtracted from the PSI value of the specific MXE (maximum Gini index of cluster) (delta PSI value) and scaled between -1 (broad tissue distribution) and 1 (highly tissue specific). Each column represents an MXE pair and each row represents MXE expression in a tissue, cell-type, or at a developmental time point. The bar graph summarizes counts where the specific MXE is 1.5 fold more spliced in than the ubiquitous MXE.",
    "ncbi_link": "MXE: 
MXEs: "
  },
  {
    "caption": "C) Heatmap showing the the delta PSI values (PSI value of the non-SNP-containing MXE subtracted from the PSI value of the SNP-containing MXE) of MXE clusters containing pathogenic SNPs scaled between -1 and 1 (blue = high expression non-SNP-containing MXE, red = high expression SNP-containing MXE). Columns represent MXE clusters and rows tissues, cell types, and developmental stages. The column bar graph summarizes counts where the SNP-containing MXE is 1.5 fold more expressed than the non-SNP-containing MXE, whereas the row bar graph shows this for each tissue, cell type, and developmental stage.",
    "ncbi_link": "MXE: "
  },
  {
    "caption": " (A) Western blotting of AXL and OPCML protein levels in AXL-expressing, OPCML-null SKOV3 and PEA1 cell lines transduced with OPCML "O" or control Empty vector "E" ",
    "ncbi_link": "AXL: 558
OPCML: 4978"
  },
  {
    "caption": "(E) Immunostaining of OPCML (red) and AXL (green) in SKOV3-OPCML and PEA1-OPCML cells. Scale bar = 10μm Data i M, (E) was performed once due to the limited numbers of primary cells;",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(G) FRET efficiency for AXL-OPCML interaction in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\", using AXL-AXL FRET as a positive control. Cells were labeled with Anti-Axl rabbit (conjugated to donor probe) and Anti-OPCML mouse (conjugated to acceptor probe), or Anti-Axl  mouse (conjugated to acceptor probe) and Anti-Axl  rabbit (conjugated to donor probe) Data in (A) to (M) are representative of at least three experiments with graphs depicting means ± SE s; *P < 0.05, ***P < 0.01, and ****P < 0.0001 by Student\"s t tests",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(H) PLA of AXL-OPCML (red) in SKOV3 and PEA1 cells transduced with empty vector "E" or OPCML "O". Scale bar = 50μm",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(L) Western blotting of membrane fractionation of SKOV3-Empty cells: total cell lysate "T", liquid-disordered soluble fraction "S", detergent resistant membrane fraction "R". Caveolin-1 is used as a marker of the R fraction and Calnexin is used as a marker for the S fraction, E: SKOV3-Empty, O: SKOV3-OPCML",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": " SKOV3-OPCML cells stimulated with Gas6 over a 12 hour time course and (A) stained with DAPI (cyan), Anti-OPCML (green) and Anti-AXL (red) antibodies (scale bar = 10μm) ",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(I) Membrane fractionation in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells into the detergent resistant \"R\" membrane fraction and the detergent soluble \"S\" fraction upon Gas6 stimulation",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(K) FRAP recovery curves in insoluble lipid domain or soluble plasma membrane fraction in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells treated with Gas6 Data in (A) to (O) are representative of at least three experiments with graphs depicting means ± SEM s; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by Student\"s t tests",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(L) Diffusion Co-efficient in insoluble lipid domain or soluble plasma membrane fraction in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells treated with Gas6 Data in (A) to (O) are representative of at least three experiments with graphs depicting means ± SEM s; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by Student\"s t tests",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(M) percentage of AXL localised in insoluble lipid domain or soluble plasma membrane fraction in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells treated with Gas6 Data in (A) to (O) are representative of at least three experiments with graphs depicting means ± SE s; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by Student\"s t tests",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(N) FRET Efficiency in SKOV3-OPCML \"O\" cells stimulated with Gas6, and labeled with Anti-Axl (donor probe) and Anti-OPCML (acceptor probe) Data in (A) to (O) are representative of at least three experiments with graphs depicting means ± SEM s; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by Student\"s t tests",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(O) Western blotting of the "S" and "R" membrane fractions in SKOV3-Empty "E" and OCPML "O" cells stimulated with Gas6 for 3 hours, for Gas6, AXL and pAXL. Data in (A) to (O) are representative of at least three experiments with graphs depicting means ± SEM",
    "ncbi_link": "OCPML: 4978"
  },
  {
    "caption": " (A) Filipin staining of SKOV3-OPCML cells treated for 30 minutes with 5mM MBCD and allowed to recover for 0, 30 minutes, and 12 hours in serum free (SF) medium",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(B) Western blotting of SKOV3-OPCML  cells treated with MBCD and separated into the detergent resistant \"R\"  membrane fraction and the detergent soluble \"S\" fraction upon Gas6  stimulation",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(C) Ratio of AXL band intensity in \"R\" or pAXL band intensity in \"S\" relative to total AXL  \"T\" from SKOV3-OPCML  \"O\" in (B)",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(D) MBCD treatment of SKOV3-EMPTY and SKOV3-OPCML cell lines was followed by the analysis of Gas6 signalling kinetics by western blot. GAPDH was used as loading control",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(E,F) Signalling kinetics are presented for pAXL and pERK in SKOV3-EMPTY "E" and SKOV3-OCPML "O", treated with MBCD and no treatment control, normalised to GAPDH, from (D)",
    "ncbi_link": "OCPML: 4978"
  },
  {
    "caption": "(G) PLA assay of AXL-OPCML interaction (red) upon Gas6 stimulation in both MBCD treated and non-treated SKOV3-OPCML cells. Scale bar = 50μm",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(B) Western Blotting of SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells pre incubated with either no drug (DMSO only control), 1.09 μM R428, or 2.84 μM R428 for an hour and stimulated with Gas6 for the indicated times. GAPDH was used as loading control",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "(C) Immunofluorescence staining of pERK (red) and OPCML (magenta) in SKOV3-Empty \"E\" and SKOV3-OPCML \"O\" cells treated with R428 and stimulated with Gas6 for the indicted time points. Scale bars = 50μm",
    "ncbi_link": "OPCML: 4978"
  },
  {
    "caption": "Representative WBs of RPE-1 wild-type (WT) cells and the two selected KO clones for AKAP450 (akap KO), PCNT (pcnt KO) and CDK5Rap2 (c5rap2 KO) probed with the indicated antibodies. GM130 was used as a loading control",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Confocal IF images of RPE-1 WT, single KO (akap KO, pcnt KO and c5rap2 KO) and double KO (pc-ak-2KO, left panels; pc-c5-2KO, right panels) cells stained with the indicated antibodies. The yellow dashed line indicates the nucleus contour (N) and the arrows point the centrosome (CTR). GA marks the Golgi Apparatus. Scale bars: 5 μm.",
    "ncbi_link": "akap: 10142
ak: 10142
c5rap2: 55755
c5: 55755
pcnt: 5116
pc: 5116"
  },
  {
    "caption": "Representative WB of RPE-1 WT cells and the two selected PCNT/AKAP450 (pc-ak-2KO) and PCNT/CDK5Rap2 (pc-c5-2KO) double knockout mutated clones probed with the indicated antibodies. GM130 was used as a loading control",
    "ncbi_link": "ak: 10142
AKAP450: 10142
c5: 55755
CDK5Rap2: 55755
pc: 5116
PCNT: 5116"
  },
  {
    "caption": "Representative WB of RPE-1 WT cells and the indicated single or double KO cell lines probed with anti-AKAP450, PCNT and CDK5Rap2 antibodies (left). Quantification of signal intensity from three independent WB experiments is shown at right. # indicates KO proteins. The arrow points the dramatic decrease of CDK5Rap2 levels in pc-ak-2KO cell line. Hsp70 was used as a loading control",
    "ncbi_link": "ak: 10142
pc: 5116"
  },
  {
    "caption": "Confocal images of WT, akap KO, c5rap2 KO, pcnt KO, pc-ak-2KO and pc-c5-2KO cells stained for EB1 (green) and the centrosomal protein CAP350 (red). High magnification single-channel images of selected areas are shown at right. Scatter plot showing quantification of EB1 comets from three independent experiments as that shown in A. A region of interest of 3 μm radius around the CAP350 signal was used to count the number of comets. Horizontal black lines represent the mean.",
    "ncbi_link": "akap: 10142
ak: 10142
c5: 55755
c5rap2: 55755
pcnt: 5116
pc: 5116"
  },
  {
    "caption": "MT regrowth experiments of WT cells mixed with either WT (as a control), akap KO, c5rap2 KO, pcnt KO, pc-ak-2KO or pc-c5-2KO cells. Samples were fixed 3 min after NZ washout and stained for EB1 (green) and the indicated protein in the red channel. Quantification of EB1 signal intensity around the centrosome",
    "ncbi_link": "akap: 10142
ak: 10142
c5rap2: 55755
c5: 55755
pcnt: 5116
pc: 5116"
  },
  {
    "caption": "WT and pc-ak-2KO cells were transfected with a combination of three siRNAs against CEP192, fixed and triple labelled for EB1, CEP192 and CAP350, as a centrosomal marker. Scramble siRNA was used as a control.",
    "ncbi_link": "ak: 10142
CEP192: 55125
pc: 5116"
  },
  {
    "caption": "Confocal images of WT, akap KO, c5rap2 KO, pcnt KO, pc-ak-2KO and pc-c5-2KO cells stained for EB1 (green) EB1 comets around the centrosome",
    "ncbi_link": "akap: 10142
ak: 10142
c5rap2: 55755
c5: 55755
pcnt: 5116
pc: 5116"
  },
  {
    "caption": "Three min MT regrowth experiments in WT and pc-ak-2KO cells transfected with either scramble or CEP192 siRNAs.",
    "ncbi_link": "ak: 10142
CEP192: 55125
pc: 5116"
  },
  {
    "caption": "MT regrowth experiments in WT and c5rap2 KO or pcnt KO cells. Cells were stained as indicated. Arrows point the centrosome.",
    "ncbi_link": "c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "WT and pc-ak-2KO cells were transfected with either scramble or CEP192 siRNAs, fixed and stained for γ-tubulin. Quantification of the fluorescence intensity is show at right.",
    "ncbi_link": "ak: 10142
CEP192: 55125
pc: 5116"
  },
  {
    "caption": "IF images of WT and pcnt KO RPE-1 cells treated with NZ for 3h and triple stained for AKAP450 (green), CDK5Rap2 (red) and GMAP210 as a Golgi marker (blue). At right, quantification of fluorescence co-localization of either AKAP450 or CDK5Rap2 with the Golgi marker GMAP210 in WT and pcnt KO cells­.",
    "ncbi_link": "pcnt: 5116"
  },
  {
    "caption": "Centrinone-treated pcnt KO, c5rap2 KO and akap KO cells, were incubated with NZ for 3h, fixed and double labelled for GM130 and either CDK5Rap2 or PCNT as indicated (n=3).",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "MT regrowth assay in centrinone-treated WT, pcnt KO and akap KO RPE-1 cells stained with antibodies to EB1 and giantin. At right, quantification of EB1 intensity at the Golgi membranes in WT and pcnt KO cells treated with centrinone, as a measure of MT-nucleation from the GA. Data were collected from two independent experiments and normalized to WT mean.",
    "ncbi_link": "akap: 10142
pcnt: 5116"
  },
  {
    "caption": "Representative MT network of a centrosome-less akap KO cell.",
    "ncbi_link": "akap: 10142"
  },
  {
    "caption": "MT-regrowth experiment after NZ treatment in centrinone-treated akap KO cells. A representative confocal image of a double labelling for EB1 (green) and giantin (blue) is shown. High magnification at right shows that growing MT asters are not associated to Golgi fragments.",
    "ncbi_link": "akap: 10142"
  },
  {
    "caption": "Centrinone-treated akap KO cells were subjected to a MT regrowth assay and double stained with the indicated antibodies. High magnification images of the boxed areas are shown as merge (top) or individual green or red labelling (middle and bottom panels).",
    "ncbi_link": "akap: 10142"
  },
  {
    "caption": "Cells lacking AKAP450 were treated with centrinone in order to induce the formation of cytoplasmic aggregates and then transfected with siRNAs specific for CDK5Rap2 (top panels) or PCNT (bottom panels). After 3-min MT regrowth, cells were fixed and stained with the indicated antibodies.",
    "ncbi_link": "AKAP450: 10142
CDK5Rap2: 55755
PCNT: 5116"
  },
  {
    "caption": "MT regrowth experiments in centrinone-treated akap KO cells transfected with either scramble or PCNT siRNAs. After a 3h NZ treatment, MTs were allowed to polymerize and, at the indicated time points after washout, cells were fixed and labelled for α-tubulin (green), PCNT (red) and CAP350 (blue).",
    "ncbi_link": "akap: 10142
PCNT: 5116"
  },
  {
    "caption": "MT repolymerization experiments in centrinone-treated akap KO cells transfected with either scramble or PCNT siRNAs. After NZ treatment and removal, cell were incubated for 10 min on ice and then warmed for 3 min in culture medium containing either DMSO or 30 μM gatastatin. Cells were finally fixed and triple stained with EB1 (green), PCNT (red) and CAP350 (blue) antibodies. Enlarged views of the boxed areas are presented at right. Scale bars, 5 μm.",
    "ncbi_link": "akap: 10142
PCNT: 5116"
  },
  {
    "caption": "Confocal images showing MT network in WT, akap KO, c5rap2 KO, pcnt KO and pc-ak-2KO RPE-1 cells fixed and stained with antibodies against α-tubulin (left) or EB1 (right). The red and yellow lines indicate the contour of cells.",
    "ncbi_link": "akap: 10142
ak: 10142
c5rap2: 55755
pcnt: 5116
pc: 5116"
  },
  {
    "caption": "Confocal images showing MT network in centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO backgrounds. Cells containing extra centrosomes induced by centrinone washout were also quantified (bottom panels).",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Quantification of α-tubulin fluorescence intensity (as a measure of MT mass polymer, C), in control and centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO cells. Non-centrinone treated double KO cells and centrinone-treated WT cells after washout were also included. Scatter plots show each individual data point and horizontal black lines bars represent the mean.",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Quantification of number of EB1 comets per cell (D) in control and centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO cells. Non-centrinone treated double KO cells and centrinone-treated WT cells after washout were also included. Scatter plots show each individual data point and horizontal black lines bars represent the mean.",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Quantification of α , cell area (E) in control and centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO cells. Non-centrinone treated double KO cells and centrinone-treated WT cells after washout were also included. Scatter plots show each individual data point and horizontal black lines bars represent the mean.",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Quantification of MT density (MT mass polymer/cell area) (F) in control and centrinone-treated WT, akap KO, c5rap2 KO and pcnt KO cells. Non-centrinone treated double KO cells and centrinone-treated WT cells after washout were also included. Scatter plots show each individual data point and horizontal black lines bars represent the mean.",
    "ncbi_link": "akap: 10142
c5rap2: 55755
pcnt: 5116"
  },
  {
    "caption": "Silencing of cis-regulated gene pairs affects GBS-induced expression of IL-6 RT-qPCR analysis of THP1-derived macrophages transduced with the indicated NC or targeting shRNAs for 72 h, infected with GBS for 1 h, and then treated with gentamicin for 30 min to terminate infection. RT-qPCR were performed at 10 h post-infection.",
    "ncbi_link": "IL-6: 3569"
  },
  {
    "caption": "Silencing of cis-regulated gene pairs affects GBS-induced expression of IL-1α (D). RT-qPCR analysis of THP1-derived macrophages transduced with the indicated NC or targeting shRNAs for 72 h, infected with GBS for 1 h, and then treated with gentamicin for 30 min to terminate infection. RT-qPCR were performed at 10 h post-infection.",
    "ncbi_link": "IL-1α: 3552"
  },
  {
    "caption": "lnc-MARCKS (B) expressions were quantified in cells stably expressing dCas9/KRAB/BFP and the NC or sgRNAs.",
    "ncbi_link": "BFP: 
lnc-MARCKS: 
Cas9: 901176"
  },
  {
    "caption": ", MARCKS (C) expressions were quantified in cells stably expressing dCas9/KRAB/BFP and the NC or sgRNAs.",
    "ncbi_link": "BFP: 
MARCKS: 4082
Cas9: 901176"
  },
  {
    "caption": "IL-6 (D) expressions were quantified in cells stably expressing dCas9/KRAB/BFP and the NC or sgRNAs.",
    "ncbi_link": "BFP: 
IL-6: 3569
Cas9: 901176"
  },
  {
    "caption": "Overexpression of lnc-MARCKS decreases MARCKS expression RT-qPCR analysis of THP1 cells transduced with lentiviruses expressing empty vector (E.V.) or lnc-MARCKS, treated with PMA overnight, and left unstimulated or stimulated with Pam3 for 8 h. Lnc-MARCKS and MARCKS expression (F)",
    "ncbi_link": "Lnc-MARCKS: 
lnc-MARCKS: 
MARCKS: 4082"
  },
  {
    "caption": "Overexpression of lnc-MARCKS enhances IL-6 expression. RT-qPCR analysis of THP1 cells transduced with lentiviruses expressing empty vector (E.V.) or lnc-MARCKS, treated with PMA overnight, and left unstimulated or stimulated with Pam3 for 8 h. IL-6 expression (G).",
    "ncbi_link": "lnc-MARCKS: 
IL-6: 3569"
  },
  {
    "caption": "lnc-MARCKS regulates MARCKS in primary macrophages. Primary macrophages were transfected with NC or lnc-MARCKS antisense oligo to knock down lnc-MARCKS expression. 48 h later, cells were stimulated with Pam3 for 8 h and harvested to detect lnc-MARCKS (H)",
    "ncbi_link": "lnc-MARCKS: 
MARCKS: 4082"
  },
  {
    "caption": "lnc-MARCKS regulates MARCKS in primary macrophages. Primary macrophages were transfected with NC or lnc-MARCKS antisense oligo to knock down lnc-MARCKS expression. 48 h later, cells were stimulated with Pam3 for 8 h and harvested to detect MARCKS (I),",
    "ncbi_link": "lnc-MARCKS: 
MARCKS: 4082"
  },
  {
    "caption": "lnc-MARCKS regulates IL-6 in primary macrophages. Primary macrophages were transfected with NC or lnc-MARCKS antisense oligo to knock down lnc-MARCKS expression. 48 h later, cells were stimulated with Pam3 for 8 h and harvested to detect IL-6 expressions (J).",
    "ncbi_link": "lnc-MARCKS: 
IL-6: 3569"
  },
  {
    "caption": "(A) ROCKI is recruited to the MARCKS promoter in Pam3-stimulated THP1-derived macrophages. ChIRP analysis of THP1-derived macrophages treated with Pam3 for 8 h. ChIRP assays were performed using a non-specific lacZ probe or probes specific for lnc-MARCKS. Specificity of ROCKI probes (left), and enrichment at the MARCKS promoter (right).",
    "ncbi_link": "lacZ: 
ROCKI: 
lnc-MARCKS: 
MARCKS: 4082"
  },
  {
    "caption": "(B) Mass spectrometry identifies APEX1 as a candidate ROCKI-binding protein in THP1-derived macrophages. APEX1 MS/MS count represents the ratio between the number of APEX1 peptides and all peptides detected. Mean of n = 2 samples. ROCKI and ROCKI-AS represent ROCKI and antisense strand of ROCKI transcripts, respectively.",
    "ncbi_link": "ROCKI: "
  },
  {
    "caption": "(C) ROCKI inhibition of MARCKS expression is dependent on APEX1. RT-qPCR analysis of MARCKS, ROCKI, and APEX1 expression in THP1-derived macrophages overexpressing ROCKI and/or depleted of APEX1.",
    "ncbi_link": "ROCKI: 
APEX1: 328
MARCKS: 4082"
  },
  {
    "caption": "(D) APEX1 specially binds to ROCKI. Western blot analysis of APEX1 in lacZ, or ROCKI pull-down fractions. Vimentin, which non-specifically binds to all RNA probes, is shown as a loading control.",
    "ncbi_link": "ROCKI: 
lacZ: "
  },
  {
    "caption": "(E) ROCKI associates with APEX1. Left: RT-qPCR analysis of ROCKI present in anti-APEX1 antibody or control IgG immunoprecipitates from nuclear lysates of Pam3-treated THP1-derived macrophages. Right: APEX1 western blot of the same immunoprecipitates.",
    "ncbi_link": "ROCKI: "
  },
  {
    "caption": "ChIP analysis of THP1-derived macrophages demonstrates APEX1 recruitment to the MARCKS promoter. RT-qPCR analysis of fragments of the MARCKS promoter region (a and b) or a non-specific region (nc) co-immunoprecipitated with anti-APEX1 antibody.",
    "ncbi_link": "MARCKS: 4082"
  },
  {
    "caption": "ChIP analysis of APEX1 recruitment to the MARCKS promoter was performed except the cells expressed control shRNA (NC) or ROCKI shRNA and treated with Pam3 for 8 h. The y-axis shows the percentage of enrichment in normalized to input. An unrelated region of the ACTB2 promoter was amplified as a control.",
    "ncbi_link": "ACTB2: 
ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "Left: Western blot analysis of APEX1 and HDAC1 in control rabbit IgG or anti-APEX1 antibody immunoprecipitates from NC (control) or ROCKI knockdown THP1-derived macrophages. Right: RT-qPCR analysis of ROCKI in the same immunoprecipitates.",
    "ncbi_link": "ROCKI: "
  },
  {
    "caption": "Knockdown of ROCKI decreased HDAC1 enrichment on the MARCKS promoter. ChIP-qPCR analysis of HDAC1 was performed using an anti- HDAC1 antibody.",
    "ncbi_link": "ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "Knockdown of ROCKI enhances H3K27ac deposition on the MARCKS promoter. ChIP-qPCR analysis of H3K27ac was performed using an anti-H3K27ac antibody.",
    "ncbi_link": "ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "Heatmap of representative genes commonly upregulated in ROCKI-overexpressing and MARCKS-knockdown THP1-derived macrophages.",
    "ncbi_link": "ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "RT-qPCR validation of inflammatory gene expression in ROCKI-overexpressing and MARCKS-knockdown THP1-derived macrophages stimulated with Pam3 for 8 h. E.V., empty vector; NC, control shRNA.",
    "ncbi_link": "ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "MARCKS is a negative regulator of Ca2+ signaling. Fluo-4 fluorescence of MARCKS, ROCKI, or NC (control) shRNA-expressing THP1-derived macrophages before and after treatment with PMA and Pam3. Triton X-100 was added to obtain the maximal [Ca2+] signal. Fluorescence levels are expressed as the change in signal normalized to the maximal fluorescence (ΔF/Fmax).",
    "ncbi_link": "ROCKI: 
MARCKS: 4082"
  },
  {
    "caption": "(A) QTL signals for ROCKI (LINC01268) gene expression in whole blood (top, black), H3K27ac promoter signal in monocytes (middle, green), and H3K4me1 signal in monocytes (bottom, orange) in a 400 kb window around the MARCKS/ROCKI locus. The signals were strongly co-localized (Pshared=.97, Pshared=.98) suggesting they represent the same signal.",
    "ncbi_link": "ROCKI: 
LINC01268: 285758
MARCKS: 4082"
  },
  {
    "caption": "(C) RT-qPCR analysis of ROCKI expression in dendritic cell samples from uninfected and M. tuberculosis-infected donors.",
    "ncbi_link": "ROCKI: "
  },
  {
    "caption": "(A) Representative 5-day-old seedlings of wild-type Arabidopsis thaliana Col-0 and TF mutants gata12 and wri3 grown in the dark. Scale bar, 1 mm.",
    "ncbi_link": "wri3: 838176
gata12: 832652"
  },
  {
    "caption": "(C) Rosette area of mutant allele of BPC4 from day 7 to day 21 post-germination. Linear model for two-way ANOVA considers AGI, salt treatment, day post-germination and their interactions. The AGI and AGI:Salt Condition terms are statistically signification (P < 0.001, P < 0.01, respectively). Heat map under line plot indicates which term in linear model is statistically significant (P < 0.05) using two-way ANOVA for each day from 9 biological replicates per condition. Solid lines, Col-0; dashed line, bpc4; circle, control condition; triangle, 50 mM NaCl.",
    "ncbi_link": "BPC4: 816663
bpc4: 816663"
  },
  {
    "caption": "A Sphere formation of GB2 cells transfected with an shRNA targeting SIRT2 was analyzed by an In Cell Analyzer 2000. Primary spheres were re-plated to evaluate secondary sphere formation. Bars indicate mean ± s.d. of 10 wells.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "B Knockdown of SIRT2 causes a decrease in the sphere formation capacity of GB16. (n = 3).",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "C mRNA levels of the indicated genes in GB2, GB4 and GB16 cells infected with a lentivirus expressing an shRNA targeting SIRT2 were measured by qRT-PCR. The results were normalized with the values for GAPDH. Bars indicate mean ± s.d. (n = 3-4).",
    "ncbi_link": "GAPDH: 
SIRT2: 22933"
  },
  {
    "caption": "The sphere formation capacity of CD133-positive and CD133-negative cells sorted by FACS directly from a tumor sample. GB17 was infected with a control (Empty) or shSIRT2-expressing (shS2 #1) lentivirus. Bars indicate mean ± s.d. of 8 wells.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "B Mice were transplanted with the indicated number of GB2 cells infected with a control (Empty) or shSIRT2-expressing (shS2 #1) lentivirus. Six weeks after transplantation, mice (3 or 4 animals, see number of dots) were sacrificed and the expression levels of human β-actin mRNA were quantified by qRT-PCR.",
    "ncbi_link": "β-actin: 60
SIRT2: 22933"
  },
  {
    "caption": "C H&E staining of tumors that were developed in mice implanted with GB16 cells that had been infected with a control (Empty) or shSIRT2-expressing (shS2#1) lentivirus. Scale bar, 1 mm. An image with higher magnification is shown on the right (scale bar, 50 μm).",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "E Ten days after intracranial transplantation of GB2 cells (1.0 × 104 cells), AK7 was intraperitoneally administrated for 4 weeks (15mg/kg, twice/week). After eight weeks, mice (4 or 5 animals, see number of dots) were sacrificed and the expression levels of human β-actin mRNA was quantified by qRT-PCR.",
    "ncbi_link": "β-actin: 60"
  },
  {
    "caption": "B Immunoblotting analysis of p73 in GB2 cells infected with a control (Empty) or shTP73-expressing lentivirus for 96 h.",
    "ncbi_link": "TP73: 7161"
  },
  {
    "caption": "Ectopic expression of the ∆N isoform of p73β suppresses the expression levels of PUMA and GADD45 induced by SIRT2 knockdown in GB2 cells. Four days after lentiviral infection, the expression levels of PUMA and GADD45 mRNA were measured by qRT-PCR. Bars indicate mean ± s.d. (n = 3).",
    "ncbi_link": "PUMA: 27113
GADD45: 4616///1647///10912
SIRT2: 22933
p73: 7161"
  },
  {
    "caption": "F HEK293 cells were transfected with TAp73α along with ΔNp73β. PUMA mRNA was measured by qRT-PCR analyses. Bars indicate mean ± s.d. (n = 3).",
    "ncbi_link": "PUMA: 27113
p73: 7161"
  },
  {
    "caption": "GB2 cells (5 × 104 cells, dashed line) were infected with the indicated lentiviruses, respectively. After 96 h, the number of viable cells was counted. shTP73 corresponds to both α and β isoforms of p73. Bars indicate mean ± s.d. (n = 4).",
    "ncbi_link": "p73: 7161
TP73: 7161"
  },
  {
    "caption": "H GB2 cells were transfected with TAp73α along with NLS-SIRT2 (nuclear-localizing mutant of SIRT2) or 3mut (deacetylase-inactive, nuclear-localizing mutant of SIRT2) and a reporter construct consisting of the promoter region of PUMA fused to a luciferase gene (Left panel). Reporter activities were determined by Dual luciferase assays (Right panel). Bars indicate mean ± s.d. (n = 3).",
    "ncbi_link": "luciferase: 
PUMA: 27113
SIRT2: 22933
p73: 7161"
  },
  {
    "caption": "I GB2 cells were electroporated with TAp73α along with NLS-SIRT2 (nuclear-localizing mutant of SIRT2) or 3mut (deacetylase-inactive, nuclear-localizing mutant of SIRT2). The expression of PUMA and GADD45 was measured by qRT-PCR analysis. Bars indicate mean ± s.d. (n = 3)",
    "ncbi_link": "PUMA: 27113
GADD45: 4616///1647///10912
SIRT2: 22933
p73: 7161"
  },
  {
    "caption": "A Cells transfected with FLAG-tagged p73 isoforms were treated with 20 μM AGK2 or DMSO for 6 h and subjected to immunoprecipitation with anti-FLAG antibody followed by immunoblotting with antibody against acetylated lysine or FLAG.",
    "ncbi_link": "FLAG: 
p73: 7161"
  },
  {
    "caption": "E HEK293T cells transfected with FLAG-tagged TAp73α were treated with 20 μM AGK2 (pre-AGK2 +) or DMSO (pre-AGK2 -) for 6 h. p73 was purified by immunoprecipitation and incubated with recombinant SIRT2 (10 U), NAD (1 mM) and/or AGK2 (3.5 μM) as indicated.",
    "ncbi_link": "FLAG: 
p73: 7161"
  },
  {
    "caption": "F qRT-PCR analysis of PUMA and GADD45 mRNA in GB2 cells infected with the indicated lentiviruses. Bars indicate mean ± s.e.m. (n = 4-5).",
    "ncbi_link": "PUMA: 27113
GADD45: 4616///1647///10912"
  },
  {
    "caption": "G Expression of p73 in (F) was determined by immunoblotting with anti-p73 antibody. RFP was used as a control.",
    "ncbi_link": "p73: 7161"
  },
  {
    "caption": "GB2 cells infected with the indicated lentiviruses were intracranially transplanted into immunocompromised mice. After 8 weeks, mice (3 to 5 animals, see number of dots) were sacrificed and the expression levels of human β-actin mRNA were quantified by qRT-PCR.",
    "ncbi_link": "β-actin: 60"
  },
  {
    "caption": "(A) HEK293 cells were transfected with DAPK ΔCaM or with a control vector (pcDNA3-luciferase, LUC), together with shRNAs targeting beclin 1 or HcRed, and with GFP-LC3 plasmid. After 72 h, cells were counted and lysates were prepared. (A) The percentage of cells with punctate GFP-LC3 fluorescence per total GFP-LC3-positive cells was quantified. Data presented are the mean±s.d. from a triplicate of 100 transfected cells. The asterisks denote a significance level of P=0.001.",
    "ncbi_link": "beclin 1: 8678
CaM: 808///805///801
DAPK: 23604
LC3: 440738///81631///84557"
  },
  {
    "caption": "(C) Representative GFP-LC3 staining of cells transfected with the control shRNA (HcRed) together with pcDNA3‐luciferase or DAPKΔCaM. CaM, calmodulin; DAPK, death‐associated protein kinase; GFP, green fluorescent protein; HEK, human embryonic kidney; shRNA, short hairpin RNA.",
    "ncbi_link": "calmodulin: 808///805///801
CaM: 808///805///801
DAPK: 23604"
  },
  {
    "caption": "(A) Flag‐tagged DAPK (100 ng) was incubated with GST (900 ng) or GST-beclin‐1 (750 ng) in the presence of Ca2+, calmodulin and [γ‐33P]ATP for 30 min or 60 min. Phosphorylated proteins were visualized by X‐ray film exposure, and GST/GST-beclin‐1 levels were visualized by Ponceau S staining. The autophosphorylation of DAPK indicates that its catalytic activity was intact in all samples.",
    "ncbi_link": "beclin‐1: 8678"
  },
  {
    "caption": "(B) Flag‐tagged DAPK (60 ng) was incubated with Flag‐tagged beclin 1 (250 ng), which was purified from HEK293T cells, and a kinase assay was performed for 60 min. Where indicated (+LiCl), beclin‐1‐bound beads were first washed stringently in 0.5 M LiCl and 0.5 M KCl. Phosphorylated proteins were visualized by X‐ray film exposure, and the levels of beclin 1 were visualized by Western blot analysis using beclin 1 antibodies. DAPK, death‐associated protein kinase; GST, glutathione S‐transferase; HEK, human embryonic kidney.",
    "ncbi_link": "DAPK: 23604"
  },
  {
    "caption": "(B) HEK293 cells were co‐transfected with Flag‐tagged beclin 1 or with Flag‐tagged beclin 1 lacking the Bcl‐2‐binding domain (ΔBD) together with Bcl‐XL and HA‐tagged DAPK. Beclin 1 was immunoprecipitated using Flag antibodies, and the co‐immunoprecipitated proteins, as well as the total cell extracts, were blotted with DAPK, Bcl‐XL and beclin 1 antibodies.",
    "ncbi_link": "Bcl‐2: 596
beclin 1: 8678"
  },
  {
    "caption": "(C) Flag‐tagged DAPK (60 ng) was incubated with GST-WT beclin 1 or with GST-T119A beclin 1 (1000 ng) in the presence of Ca2+, calmodulin and ATP for 30 min. GST‐beclin 1 levels were visualized by Ponceau S staining, and phosphorylation on Thr 119 was detected by a phosphoThr 119 antibody (Western blot).",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(D) HEK293 cells were co‐transfected with Flag‐tagged beclin 1 with or without ΔCaM DAPK. After 24 h, beclin 1 was immunoprecipitated from cells, using Flag antibodies, and the immunoprecipitates were reacted with phosphoThr 119 antibodies. The Ponceau staining shows equal amounts of immunoprecipitated beclin 1. The cell extract blots were reacted with haemagglutinin antibodies or with beclin 1 antibodies. CaM, calmodulin; DAPK, death‐associated protein kinase; GST, glutathione S‐transferase; HEK, human embryonic kidney; TCA, trichloro‐acetic acid.",
    "ncbi_link": "CaM: 805///801///808
DAPK: 23604"
  },
  {
    "caption": "(B) HEK293 cells were co‐transfected with Flag‐tagged T119A or T119E beclin 1 mutants and Bcl‐XL. Beclin 1 was immunoprecipitated using Flag antibodies, and the co‐immunoprecipitated proteins, as well as the total cell extracts, were blotted using the indicated antibodies.",
    "ncbi_link": "Beclin 1: 8678"
  },
  {
    "caption": "(C) HEK293 cells were transfected with 5 or 10 μg T119A or T119E beclin 1 mutants together with GFP-LC3 plasmid. After 24 h, cells were counted and lysates were prepared. (a) Representative GFP-LC3 staining. (b) The percentage of cells with punctate GFP-LC3 fluorescence per total GFP-LC3‐positive cells was quantified. Data presented are the mean±s.d. from a triplicate experiment with 100 transfected cells. The asterisks denote significance level: *P=0.01; **P=0.005. (c) Western blot analysis was performed using the indicated antibodies.",
    "ncbi_link": "beclin 1: 8678
LC3: 81631///84557///440738"
  },
  {
    "caption": "(D) HEK293 cells were transfected with Bcl‐XL, Flag‐tagged beclin 1 (WT) or Flag‐tagged T119A beclin 1 mutant with or without haemagglutinin‐tagged activated DAPK (ΔCaM). Beclin 1 was immunoprecipitated using Flag antibodies, and the co‐immunoprecipitated proteins, as well as the total cell extracts, were blotted using the indicated antibodies. Levels of Bcl‐XL were quantified using NIH image software, and the ratio between immunoprecipitated and expressed Bcl‐XL was calculated.",
    "ncbi_link": "beclin 1: 8678
CaM: 805///801///808"
  },
  {
    "caption": "(E) Transmission electron micrographs of HEK293 cells 24 h after they were transfected with Bcl‐XL, Flag‐tagged beclin 1 and ΔCaM or pcDNA3‐luciferase as a control. The images in (c) and (d) were taken at higher magnifications of the ΔCaM treatment (see the scale bars). 'AV' indicates autophagic vacuoles. CaM, calmodulin; DAPK, death‐associated protein kinase; GFP, green fluorescent protein; GST, glutathione S‐transferase; HEK, human embryonic kidney; NIH, National Institutes of Health.",
    "ncbi_link": "Bcl‐XL: 598
beclin 1: 8678
CaM: 805///801///808
DAPK: 23604"
  },
  {
    "caption": "A) Visualisation of the pathology load at 9M of age of TAUwt, TAUtg and APPtg mice at 9M of age. Immunofluorescent staining for X34 (a fluorescent derivative of Congo Red), Iba1 (microglia) and TO-PRO-3 (nuclei) has been pseudocolored. Scale bar = 100μm.",
    "ncbi_link": "APP: 351
TAU: 17762
TAU: 4137"
  },
  {
    "caption": "Log2 fold change (LFC) in TAUtg (x-axis) and APPtg mice (y-axis) after differential expression analysis. Upregulated genes are on the right part (TAUtg mice) or upper part (APPtg mice) of the graph; downregulated genes are on the left part (TAUtg) or lower part (APPtg) of the graph. Colored dots represent significantly differentially expressed genes (Benjamini-Yuketieli-adjusted p-values (Padj) <0.05) for APPtg (green dots), TAUtg (yellow dots) or for both (red dots). Spearman correlation assesses the correlation between APPtg and TAUtg mice when ranking genes that are significantly differentially expressed in either APPtg or TAUtg mice from most up- to most down-regulated on a combined score of LFC and padj (i.e. signed log10(p-value), where the sign is determined by the LFC). A) Genes differentially expressed as a function of age, i.e. 4M vs 10M, independently of genotype. Thus, genes with a positive LFC are more highly expressed in 10M mice over 4M mice. ",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "Log2 fold change (LFC) in TAUtg (x-axis) and APPtg mice (y-axis) after differential expression analysis. Upregulated genes are on the right part (TAUtg mice) or upper part (APPtg mice) of the graph; downregulated genes are on the left part (TAUtg) or lower part (APPtg) of the graph. Colored dots represent significantly differentially expressed genes (Benjamini-Yuketieli-adjusted p-values (Padj) <0.05) for APPtg (green dots), TAUtg (yellow dots) or for both (red dots). Spearman correlation assesses the correlation between APPtg and TAUtg mice when ranking genes that are significantly differentially expressed in either APPtg or TAUtg mice from most up- to most down-regulated on a combined score of LFC and padj (i.e. signed log10(p-value), where the sign is determined by the LFC). B) Genes differentially expressed due to genotype, i.e. WT vs TG, independently of age. Thus, genes with a positive LFC are more highly expressed in TG mice than in WT mice.",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "Log2 fold change (LFC) in TAUtg (x-axis) and APPtg mice (y-axis) after differential expression analysis. Upregulated genes are on the right part (TAUtg mice) or upper part (APPtg mice) of the graph; downregulated genes are on the left part (TAUtg) or lower part (APPtg) of the graph. Colored dots represent significantly differentially expressed genes (Benjamini-Yuketieli-adjusted p-values (Padj) <0.05) for APPtg (green dots), TAUtg (yellow dots) or for both (red dots). Spearman correlation assesses the correlation between APPtg and TAUtg mice when ranking genes that are significantly differentially expressed in either APPtg or TAUtg mice from most up- to most down-regulated on a combined score of LFC and padj (i.e. signed log10(p-value), where the sign is determined by the LFC). C) Genes differentially expressed in the age*genotype interaction comparison, i.e. comparing the TG-10M mice to all other experimental groups (see Fig.1C). Thus, genes with a positive LFC are more highly expressed in the TG-10M mice compared to all other experimental groups.",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "Log2 fold change (LFC) in TAUtg (x-axis) and APPtg mice (y-axis) after differential expression analysis. Upregulated genes are on the right part (TAUtg mice) or upper part (APPtg mice) of the graph; downregulated genes are on the left part (TAUtg) or lower part (APPtg) of the graph. Colored dots represent significantly differentially expressed genes (Benjamini-Yuketieli-adjusted p-values (Padj) <0.05) for APPtg (green dots), TAUtg (yellow dots) or for both (red dots). Spearman correlation assesses the correlation between APPtg and TAUtg mice when ranking genes that are significantly differentially expressed in either APPtg or TAUtg mice from most up- to most down-regulated on a combined score of LFC and padj (i.e. signed log10(p-value), where the sign is determined by the LFC). D) Depicts the 314 Marioni-based GWAS genes at p<0.001 onto the LFC/LFC plot of the age*genotype comparison (panel C). Green dots are significantly changed.",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "B) Log2 fold change (LFC) in TAUtg (x-axis) and APPtg mice (y-axis) after differential expression analysis, assessing the effects of age*genotype interaction. Color code for dots/numbers: grey = genes in hippocampus (n=15824); black = genes in APPtg-Blue (n=4236); green = genes significantly differentially expressed in APPtg mice (n=493); yellow = significantly differentially expressed genes in TAUtg mice (n=9); red = significantly differentially expressed genes in both (n=9).",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "C) Z-score distribution per experimental group for all genes within the APPtg-Blue module. Boxplots: center line, median; box limits, 25th-75th quartiles; whiskers, 1.5x interquartile range. Empirical p-values are Bonferroni adjusted (***pbonf<0.001) and indicate significant shift in z-score distribution",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "B) Distribution of cells across the different clusters per experimental group (n=2 mice pooled for all experimental groups, except for TAUtg-11M and TAUwt-11M with n=3 mice pooled).",
    "ncbi_link": "TAU: 4137"
  },
  {
    "caption": "C) Distribution of cells per experimental group over the different clusters, expressed in percentages as stated on top of each bar. E.g. of all cells within APPtg-11M, 56.7% of cells are ARM, while 12.5% are HM.1 cells.",
    "ncbi_link": "APP: 351"
  },
  {
    "caption": "E) Differential expression of ARM vs HM.1 microglia for APPtg and TAUtg mice separately. Genes with a positive log(fold change) (LFC) are higher expressed in ARMs compared to HM.1 microglia. As can be seen which genes are more highly expressed in ARMs vs HM.1 cells are highly similar among APPtg and TAUtg mice (Spearman correlation r=0.91, p=2.2e-16). LFC > |0.2| with padj<0.05 are considered significant.",
    "ncbi_link": "APP: 351
TAU: 4137"
  },
  {
    "caption": "C: Surface expression of TRAP mutants on fixed but not permeabilized sporozoites. Differential interference contrast (DIC) and immunofluorescence images of representative examples of hemolymph derived sporozoites of the indicated parasite lines stained with anti-TRAP antibodies shown in red Hoechst was used to reveal the sporozoite nuclear DNA shown in blue. Cytoplasmic GFP or staining with anti-CSP antibodies was used to validate the integrity of sporozoites. Scale bar: 5 µm.",
    "ncbi_link": "TRAP: 55150523"
  },
  {
    "caption": "D: Percentage of gliding and non-gliding control hemolymph sporozoites (HLS) at increasing concentrations of DTT. n indicates the number of observed sporozoites. Floaters are included in the non-motile fraction. Each condition represents pooled data from 2 biological replicates. Shown is the mean +/- SEM. E: Percentage of gliding hemolymph sporozoites (HLS) expressing the open TRAP I domain at increasing concentrations of DTT. n indicates the total number of observed sporozoites. Floaters are included in the non-motile fraction. Shown are pooled data from 3 (0mM DTT), 2 (50mM DTT), and 3 biological replicates for concentrations of 100mM DTT in the S210C/Q216C line. For concentrations of 200mM and 330mM DTT in the S210C/Q216C line, data shown represent pooled data from 1 biological replicate. Several comparable screening experiments previously performed showed no productive motility at these concentrations. Shown is the mean +/- SEM.",
    "ncbi_link": "TRAP: 55150523"
  },
  {
    "caption": "(B) In vivo epifluorescence microscopy following de novo expressed UapA-GFP in a single growing germling, at 70, 80, 100, 120, 140, 160 and 170 min after derepression of transcription via its native uapA promoter (for details see text and Materials and methods). Notice that in the growing germling tip UapA localizes in a membranous mesh and some cytosolic puncta whereas in more tip-distal parts of the germlings UapA is in PM-localized puncta (see white arrows), which progressively become more abundant so that at more posterior areas the PM is homogeneously labeled.",
    "ncbi_link": "uapA: 2870384"
  },
  {
    "caption": "(C) In vivo epifluorescence microscopy following de novo expressed UapA-GFP in a germling maturing to young hypha at 180, 240, 300, 360 and 400 min after derepression of transcription via its native uapA promoter. During this developmental transition, UapA apical localization is gradually diminished. As the cell tip acquires a faster growth rate, UapA is completely retracted from the hyphal apex (see zoon-in panels on the right and white arrows).",
    "ncbi_link": "uapA: 2870384"
  },
  {
    "caption": "(F) In vivo epifluorescence microscopy following neosynthesized alcAp-UapA-GFP in a single hypha at 120, 130, 140, 150, 160 and 170 min, under overexpressing (derepression/ethanol-induction) conditions, as described in Materials and methods. Notice that UapA labels the perinuclear ER rings (white arrows).",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(G) In vivo epifluorescence microscopy following de novo expressed alcAp-GFP-SynA in a single young hyphal cell, at 60, 70, 80, 90 and 100 min after transcriptional derepression (for strain details see Materials and methods). SynA is a standard polar membrane cargo that traffics to the hyphal tip via Golgi-dependent secretion. Notice the very distinct GFP fluorescent signals obtained using UapA (non-polar membrane network and PM) versus SynA (Golgi-like puncta and polar depositioning at the tip; see also alter).",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(A, B) Co-localization analysis of neosynthesized alcAp-UapA-GFP with early (SedV) or late (PHosbp) markers, respectively, tagged with mCherry or mRFP. Images show single hyphal cells. For conditions of transcriptional derepression see Materials and methods. Quantification of co-localization was performed by calculating Pearson's Correlation Coefficient (PCC). One sample t-test was performed to test the significance of differences in PCCs. Biological/technical replicates:2/9 for alcAp-UapA-GFP mCherry-SedV and 2/8 for alcAp-UapA-GFP mRFP-PHosbp. For the definition of the two categories of replicates see Materials and methods. Results of quantification, shown on the middle, suggest that there is no significant overlapping fluorescent signal of UapA with SedV (PCC=0.25±0.09, P<0.0001) or with PHOSBP (PCC=0.34±0.06, P<0.0001), as PCC values close to 0.2-0.3 are also commonly obtained when distinct compartments (e.g. ER and early Golgi or early and late Golgi) are followed with different fluorophores. Scale bars: 2 μm.",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(C, D) Co-localization analysis of neosynthesized alcAp-GFP-SynA, used as a conventional cargo that traffics through the Golgi, with early (SedV) or late (PHospb) markers tagged with mCherry or mRFP, respectively. Images show single hyphal cells. For conditions of transcriptional derepression see Materials and methods. Quantification of co-localization and statistical analysis was performed as in (A, B). Biological/technical replicates: 2/10 for each strain. Statistical analysis showed significant colocalization of SynA with the late Golgi marker (PCC = 0.67±0.04, P<0.0001), but not with early Golgi marker (PCC=0.37±0.06, P<0.0001). An explanation for lack of co-localization of SynA with SedV is given in the text. Scale bars: 2 μm. The cartoon at the bottom depicts the localization of early or late markers as established here in several previous studies",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(B) Key endogenous genes controlling Golgi (sedV, geaA, hypB) or post-Golgi trafficking (rabE, ap1σ, claH) were genetically replaced by versions transcribed under the highly repressible thiAp promoter via targeted homologous recombination. In the absence of thiamine from the growth medium (derepressed conditions) the relative proteins are expressed, while upon addition of thiamine at the onset of conidiospore germination (ab initio repression) the expression of these proteins is tightly repressed. Proteins are detected by a standard western blot analysis using either anti-FLAG or anti-GFP antibodies for Golgi and Post-Golgi proteins. Equal loading and protein steady state levels are normalized against the amount of actin, detected with a specific antibody.",
    "ncbi_link": "thiA: "
  },
  {
    "caption": "(C) In the absence of thiamine from the growth medium (derepressed conditions) the corresponding strains grow nearly as an isogenic wild-type control, although a delay in growth is observed for thiAp-sedV and less so for thiAp-ap1σ (upper row). In the presence of thiamine to the growth medium most cells do not form colonies, except for thiAp-hypB which forms a compact slow growing colony (lower row).",
    "ncbi_link": "ap1σ: 
hypB: 
sedV: 
thiA: "
  },
  {
    "caption": "(D) Microscopic examination of the corresponding strains under thiamine (repressing conditions) shows that, in most cases, the apical region of germlings is enlarged and growth is arrested. This morphological phenotype, taken as a strong indication of blocked secretion, is more evident in thiAp-sedV and thiAp-rabE but concerns all strains, except for thiAp-hypB. Scale bar: 5 μm.",
    "ncbi_link": "hypB: 
rabE: 
sedV: 
thiA: "
  },
  {
    "caption": "(E) Subcellular localization of UapA, after 6-8 hours of initiation of transcription, via its native uapA promoter, while conventional sedV, geaA or hypB transcription is repressed by thiamine ab initio. Scale bars: 2 μm. Notice that UapA-GFP translocates in the PM of germlings in all cases. Results shown are confirmed by quantification (right panel) of UapA-GFP PM/cytosolic intensity ratios for the four strains (for details see Materials and methods). Mean PM/cytosolic intensity ratios for wild-type, thiAp-sedV, thiAp-geaA and thiAp-hypB are 0.53±0.02, 0.52±0.02, 0.52±0.02 and 0.52±0.02, respectively. For the statistical analysis, Tukey's Multiple Comparison test was performed (One-way ANOVA). No statistical significance was found between the wild-type and each of the mutant strains. Biological/technical replicates: 3/15 for wild-type, 3/18 for thiAp-sedV, 3/15 for thiAp-geaA and 3/18 for thiAp-hypB.",
    "ncbi_link": "hypB: 
geaA: 
sedV: 
thiA: 
uapA: 2870384"
  },
  {
    "caption": "(F) alcAp-UapA-GFP, under derepressing conditions, translocates to the PM of a strain carrying a thermosensitive mutation in SedVts both at the permissive (25oC) and restrictive temperature (42oC). A degree of increased degradation of UapA, caused by exposure to high temperature (42oC), is apparent as cytosolic puncta, which correspond to membrane aggregates and sorting to vacuoles. Scale bar: 5 μm.",
    "ncbi_link": "SedV: 
alcA: 2868277"
  },
  {
    "caption": "(G) Unlike UapA, de novo made apical markers, such as ChsB or SynA, lose their polar localization, when the expression of sedV, geaA or hypB is repressed. Scale bars: 2 μm. Quantification: GFP-ChsB PM/cytosolic and alcAp-GFP-SynA PM/cytosolic intensity ratios are plotted to the right upper and lower panel, respectively. For GFP-ChsB, mean PM/cytosolic intensity ratios are: 0.60±0.02 (wild-type), 0.11±0.01 (thiAp-sedV), 0.26±0.02 (thiAp-null) and 0.34±0.01 (thiAp-hypB). For alcAp-GFP-SynA mean PM/cytosolic intensity ratios for wild-type, thiAp-sedV, thiAp-geaA and thiAp-hypB are 0.61±0.03, 0.14±0.02, 0.26±0.03 and 0.39±0.03, respectively. The statistical analysis was performed as in (E). A significant difference (****P<0.0001) of GFP-ChsB fluorescence in the apical PM membrane was found between the wild-type and the three strains lacking the key-Golgi proteins. This is also the case for SynA, as seen in the scatter plot on the lower right panel, where the fluorescence intensity of SynA is diminished (****P<0.0001) when sedV, geaA and hypB are repressed. Biological/technical replicates: 3/15 for each strain.",
    "ncbi_link": "hypB: 
geaA: 
sedV: 
thiA: 
alcA: 2868277"
  },
  {
    "caption": "(A) Growth test showing that Sec24 expression is essential for growth as its transcriptional repression by thiamine (+thi) leads to absence of colony formation, despite initial germination The strains shown are isogenic except for the sec24 locus. thiAp-sec24 signifies the strain where the endogenous sec24 promoter was replaced by the thiAp promoter.",
    "ncbi_link": "sec24: 
thiA: "
  },
  {
    "caption": "(B) Epifluorescence microscopy analysis of the subcellular localization of UapA-GFP under conditions where sec24 transcription is ab initio derepressed (upper panel) or repressed by thiamine (lower panel). o/n (overnight) means addition of thiamine from the onset of germination. Germination of conidiospores takes place until full repression of Sec24 is achieved (10-12 h). Notice the total lack of PM-associated signal of UapA under conditions of Sec24 repression. Scale bar: 5 μm. Quantification: In the scatter plot on the right, UapA-GFP PM/cytosolic intensity ratios are quantified when sec24 is derepressed (-thi) or repressed (+thi). Mean PM/cytosolic intensity ratios are 0.55±0.02 and 0.32±0.02 respectively. To test the significance of differences, an unpaired t-test was performed, which verified the significant difference (****P<0.0001) in the presence of thiamine. Biological/technical replicates: 2/15 for each condition.",
    "ncbi_link": "sec24: "
  },
  {
    "caption": "(E) Epifluorescence microscopy analysis of the subcellular localization of UapA-GFP under conditions where sec13 transcription is ab initio derepressed (left panel) or repressed by thiamine (right panel). The inserts in the upper right corner in both panels reflect growth tests showing that Sec13 repression leads to arrest in growth and absence of colony formation. Scale bars: 5 μm. All images reflect practically identical results obtained in several experiments. Quantification: UapA-GFP PM/cytosolic intensity ratios are quantified when sec13 is derepressed (-thi) or repressed (+thi), with mean values being 0.54±0.02 and 0.31±0.02, respectively. There is a significant difference on UapA PM fluorescence intensity (****P<0.0001) in the absence of the COPII outer coat protein (statistical analysis as in B). Biological/technical replicates: 2/15 for each condition.",
    "ncbi_link": "sec13: "
  },
  {
    "caption": "(A) Epifluorescence microscopy analysis examining the subcellular localization of de novo made UapA-GFP, after 6-8 hours of initiation of transcription in strains where the expression of RabE, AP-1σ or ClaH (thiAp-rabE, thiAp-ap1σ or thiAp-claH) has been repressed ab initio (o/n) by addition of thiamine. Notice that when rabE or ap1σ is repressed UapA-GFP still reaches the PM. In contrast, repression of claH abolishes labeling of the PM and leads to the cytosolic puncta and a membranous network. Scale bars: 5 μm. Quantification: UapA-GFP PM/cytosolic intensity ratios are plotted on the right. Mean ratios for wild-type, thiAp-rabE, thiAp-ap1σ and thiAp-claH are 0.55±0.02, 0.53±0.03, 0.54±0.02 and 0.29±0.02 respectively. For the statistical analysis, Tukey's Multiple Comparison test was performed (One-way ANOVA). After 6-8h of transcriptional derepression, UapA-GFP fluorescence to the PM does not change when rabE or ap1σ are repressed. On the other hand, in the absence of ClaH, UapA does not reach the PM, as its fluorescence intensity there is statistically lower (****P<0.0001) in comparison to that of the wild-type strain. Biological/technical replicates: 2/15 for each strain.",
    "ncbi_link": "claH: 
rabE: 
ap1σ: 
thiA: "
  },
  {
    "caption": "(B) In a similar experiment, the apical polarized localization of de novo made SynA, used as a control of conventional secretion, is shown to be abolished in all three strains where RabE, AP-1σ or ClaH are repressed. Scale bars: 5 μm. mCherry-SynA PM/cytosolic intensity ratios are plotted with values being 0.52±0.02 for wild-type, 0.14±0.02 for thiAp-rabE, 0.24±0.02 for thiAp-ap1σ and 0.16±0.02 for thiAp-claH. The statistical evaluation was performed as in (A). There is a significant difference (****P<0.0001) of mCherry-SynA fluorescence in the apical PM membrane between the wild-type and the three strains lacking the post-Golgi proteins. Biological/technical replicates: 2/15 for each strain.",
    "ncbi_link": "ap1σ: 
claH: 
rabE: 
thiA: "
  },
  {
    "caption": "(B) Time course of treatment of strains expressing neosynthesized alcAp-UapA-GFP and mCherry-TubA with the anti-microtubule drug benomyl for 5, 55, or 95 minutes. In all cases benomyl was added at 95 min of UapA derepression, so that total time of UapA-GFP expression was 100, 150 or 190 minutes Benomyl abolished the thread-like appearance microtubules in all samples added, evident by the diffuse cytoplasmic signal of mCherry-TubA. Notice that UapA reaches normally the PM (at 190 min of derepression), similarly to the untreated control (right panel). Scale bar: 5 μm.",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(C) Subcellular localization of neosynthesized alcAp-GFP-ChsB in the absence (left panel) or presence (≈40 min) of benomyl (middle panel) or latrunculin B (right panel), after ≈2h of derepression. Notice the abolishment of proper polar localization of ChsB at the apical tip in both cases. Scale bars: 5 μm.",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(A) Subcellular localization of de novo made alcAp-GFP-SsoA in the PM in a single hypha. Notice the ER-like membranous network (white arrows) and several cytosolic puncta labelled before SsoA reaches eventually the PM. Scale bar: 5 μm.",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "(B) Subcellular localization of neosynthesized UapA-GFP (8 hours after transcriptional depression) while ssoA transcription is ab initio repressed. Notice the localization of UapA in the ER-membranous network, often at very close proximity with the PM. Scale bar: 5 μm. In the scatter plot on the right, UapA-GFP PM/cytosolic intensity ratios are quantified when ssoA is derepressed (-thi) or repressed (+thi), with mean values being 0.54±0.02 and 0.30±0.02 respectively. There is statistically lower fluorescence intensity to the PM (****P<0.0001) when SsoA is absent from the cell, as confirmed by an unpaired t-test. Biological/technical replicates: 2/15 for each condition.",
    "ncbi_link": "ssoA: "
  },
  {
    "caption": "(A) Epifluorescence microscopy analysis examining the subcellular localization of de novo made alcAp-AzgA-GFP and alcAp-FurA-GFP, after 6-8 hours transcriptional derepression in strains where the expression of Sec24, SedV, GeaA, HypB, RabE, AP-1σ and SsoA was repressed ab initio (o/n) by addition of thiamine. Images showing that sorting of AzgA or FurA to the PM does not require early (SedV, GeaA), late (HypB) or post-Golgi (RabE, AP-1σ ) key proteins. On the other hand, COPII coat protein Sec24 and PM t-SNARE SsoA are essential for proper localization of the two transporters to the PM. Scale bar: 5 μm.",
    "ncbi_link": "alcA: 2868277"
  },
  {
    "caption": "Keratinocytes were isolated from the skin of a 4-year-old patient with severe-generalised RDEB linked to homozygous insertion-deletion in COL7A1 (Hilal et al, 1993). Cultured RDEB cells (blue line) were serially passaged for more than 4 months, displaying a growth potential similar to non-diseased control cells (YF29) isolated from the foreskin of a newborn (black line). To calculate the percentage of growing colonies, 100 to 1,000 cells were plated into indicator dishes at each passage. Cells were grown for 12 days, fixed and stained with rhodamine B. Colonies were scored as growing or aborted (Barrandon & Green, 1987).",
    "ncbi_link": "COL7A1: 1294"
  },
  {
    "caption": "Single cells were isolated from a mass culture (passage V) of RDEB keratinocytes infected with SIN retroviruses bearing a COL7A1 cDNA. Clonal types were determined (Barrandon & Green,1987) and listed in Supplementary Table S1. Growing clones were expanded for further characterisation.COLVII detection in clones by immunostaining. COLVII expression (green) was detectable in some clones (6, 17, 22, 58 and 61) and not in others (3, 24 and 54); nuclei were stained with Hoechst 33342 (blue). Dotted lines delimit the periphery of keratinocyte colonies from the surrounding irradiated 3T3-J2 feeder cells. Scale bar: 50 μm.",
    "ncbi_link": "COL7A1: 1294"
  },
  {
    "caption": "Single cells were isolated from a mass culture (passage V) of RDEB keratinocytes infected with SIN retroviruses bearing a COL7A1 cDNA. Clonal types were determined (Barrandon & Green,1987) and listed in Supplementary Table S1. Growing clones were expanded for further characterisation. Quantitative RT-PCR analysis of COL7A1 expression in transduced clones compared to untransduced RDEB keratinocytes. All clones shown in (A) were transduced but expressed different levels of COL7A1 transcripts. Clones 6, 17, 22, 54, 58 and 61 expressed higher levels of COL7A1 than control RDEB cells and keratinocytes obtained from healthy donors (YF29 and OR-CA, control 1 and 2, respectively). The level of COL7A1 expression in the RDEB untransduced cells was referenced as 1.",
    "ncbi_link": "COL7A1: 1294"
  },
  {
    "caption": "Single cells were isolated from a mass culture (passage V) of RDEB keratinocytes infected with SIN retroviruses bearing a COL7A1 cDNA. Clonal types were determined (Barrandon & Green,1987) and listed in Supplementary Table S1. Growing clones were expanded for further characterisation. Determination of proviral rearrangements in transduced clones. A Southern blot was performed using genomic DNA of RDEB cells, clones and the infected mass culture from which the clones were isolated. Genomic DNA was digested with EcoRV and SpeI that cut at the 3′ and 5′ end of the provirus (Supplementary Fig S2) and hybridised with a 907-bp COL7A1 probe radiolabelled with 32P isotope. The upper band corresponded to the endogenous signal. The retroviral producer line Flp293A-E1aColVII1 was used as a control for the digested 9.6-kb provirus (proviral signal). Smaller bands corresponded to rearranged proviruses marked with an asterisk.",
    "ncbi_link": "ColVII1: 1308
COL7A1: 1294"
  },
  {
    "caption": "Single cells were isolated from a mass culture (passage V) of RDEB keratinocytes infected with SIN retroviruses bearing a COL7A1 cDNA. Clonal types were determined (Barrandon & Green,1987) and listed in Supplementary Table S1. Growing clones were expanded for further characterisation. Identification of stem cells producing COLVII. Western blotting revealed that only clone 6 secreted COLVII in the culture supernatant, while clone 54 and surprisingly clone 22 did not (see A). RDEB cells were used as a negative control and healthy donor cells as a positive control. The secreted matrix metalloproteinase 2 (MMP2) was used as a loading control.",
    "ncbi_link": "COL7A1: 1294"
  },
  {
    "caption": "Serial cultivation of transduced and untransduced holoclones demonstrated that the growth potential of the stem cells was not affected by the production of COLVII. Non-COLVII-producing holoclone 54 (black lines) and COLVII-producing holoclone 6 (red lines) were serially transferred once a week until exhaustion (Rochat et al, 1994).Theoretical number of epidermal cells available for characterisation and CEA production from corrected (clone 6) and uncorrected stem cells (clone 54) calculated from the day of cloning. The colony-forming efficiency and the percentage of growing colonies for each passage were used to calculate the population doubling, the generation number and the total progeny of isolated stem cells. Both corrected and uncorrected epidermal stem cells show high growth potential in vitro.",
    "ncbi_link": "COLVII: 1308"
  },
  {
    "caption": "Immunodeficient SCID mice were transplanted with untransduced cultured RDEB keratinocytes (left) or the COLVII-secreting holoclone (clone 6) (right). Punch biopsies were obtained at various times post-transplantation (PT), stained with haematoxylin/eosine (H/E), for human leucocyte antigen-1 (HLA-1) (green) and human COLVII (red). RDEB keratinocytes generated a HLA-1-positive epidermis that adhered poorly to the dermo-epidermal junction (DEJ) (arrow indicates a blister) and absence of COLVII (dotted line delimits the dermis), whereas the corrected keratinocytes produced an epidermis that adhered to the dermis and deposited COLVII (red) at the DEJ. Note the presence of KI67-positive keratinocytes (red) in the basal and suprabasal layers in the corrected epidermis at 385 days post-transplantation, indicating that transplanted cells had self-renewed for more than a year. Scale bar: 50 μm.",
    "ncbi_link": "COLVII: 1308"
  },
  {
    "caption": "Visualisation of COL7A1 sequence by FISH analysis in corrected stem cells at passage XII (clone 6). Five specific signals (red) were detected on five different chromosomes. As expected, a COL7A1 probe (red) hybridised to the two endogenous COL7A1 alleles located on the chromosomes 3 as identified by a specific centromeric probe (Cen 3) and to three other chromosomes identified as chromosomes 2, 11 and 22 by means of specific centromeric probes (Cen 2, Cen 11 and Cen 22, respectively). The latter corresponded to proviruses.Determination of proviral integration sites in corrected stem cell. Genomic DNA from clone 6 was submitted to whole-genome sequencing together with PCR and subsequent Sanger sequencing to identify the integration sites to the base-pair level. Mate pairs that span from the viral sequence to a human chromosome were extracted and used to estimate integration regions. The reads were mapped to the hg19 reference sequence. Three integration sites were uncovered: one in chromosome 2, one in chromosome 11 and one in chromosome 22, and targeted genes were identified.",
    "ncbi_link": "COL7A1: 1294"
  },
  {
    "caption": "Analysis of the level of expression of targeted genes in corrected stem cells by quantitative RT-PCR. DARS was not significantly changed in clone 6 compared to the cells before transduction. Primers used annealed downstream of the proviral integration site. Error bars represent the standard deviation of three replicates.Identification of sequence abnormalities in the two alleles of the DARS-targeted gene in clone 6 by NGS. Reads were mapped to the hg19 reference sequence. Small insertion-deletions and SNP calling were performed and compared to GWAS databases. The mapping highlighted two indels and one SNP in the DARS genomic sequence. The indels were not associated with disease and the SNP was synonymous (CCU-CCG both codons correspond to proline).",
    "ncbi_link": "DARS: 1615"
  },
  {
    "caption": "To test whether the transduced RDEB keratinocytes had disseminated after the generation of an epidermis onto SCID mice (see Fig4C), the internal organs of the recipient mice (3 mice for clone 6 and 2 mice for clone 22) were harvested 385 days post-transplantation and analysed for COL7A1 proviral sequences. No COL7A1 sequence was detected. A mouse transplanted with a holoclone obtained from a healthy donor (YF29) was used as an internal control. PCR-positive controls were genomic DNA from transduced cells (holoclone 6) and cDNAs isolated from healthy keratinocytes. B-actin was run as a loading control.",
    "ncbi_link": "B-actin: 
COL7A1: 1294"
  },
  {
    "caption": "C. Representative  flow cytometric profiles of  thymocytes from 6-week old  Rb∆K4 and control  mice  for CD3-, CD4- and  CD8-positive cell populations. Bottom, average of CD3-, CD4- and  CD8 single- and double-positive cells in Rb∆K4 vs. control  thymocytes showing no significant (n.s.) difference by student's t-test. Bars represent mean ±SD (standard deviation); n=6 biological replicates).",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "D. Short telomeres in Rb∆K4 mice. Images of  splenocyte metaphase spreads hybridized with the telomere repeat probe (pink). Note shorter telomeres in Rb∆K4 splenocytes  (arrows). Bottom, quantitative analysis of 10  splenocyte metaphases from one pair of Rb∆K4 and control littermate; (P<0.001 by two-tailed Mann-Whitney-Wilcoxon test).",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "C. Left, representative  flow cytometric analysis for CD3, CD4 and CD8, showing near normal  T cell  development in 10-day-old Rb∆K7 mice. Right, average of CD3, CD4  and CD8 single- and double-positive cell populations in Rb∆K7 vs control thymocytes  with no significant difference (n.s.) by student's t-test. Results are presented as mean ±SD, n=4 biological replicates).",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "D. Left, images showing apparent normal division of  retinal progenitors in  Rb∆K7 mice. Mice were labeled with BrdU for 2 hrs; retinal sections from indicated genotypes were stained  with  DAPI (blue), Ki67 (green), PH3  (red) or  BrdU (red) to mark nuclei, all dividing cells, mitotic  or S-phase cells, respectively. Right, quantification of  staining showing no significant difference among the genotypes. Bars denote mean ±SD; n=3 biological replicates). Scale bar: 20 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "E. Left, top,  western blot analysis of Rb∆K7 thymocytes with an antibody that recognizes both hyper-phosphorylated (ppRb) and hypo-phosphorylated pRb species. Right, phospho-specific  immunoblots showing absence of phosphorylation at upstream Thr350 and Ser601 or the substituted Ser773Ala site in  Rb∆K7 thymocytes. Right, immuno-precipitation (IP)-Western blot  analysis demonstrating  phosphorylation of  pRb∆K7 on Ser243/Thr246 (top) and Ser605 (bottom). n.s., non-specific band.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "B. Increased resistance of  Rb∆K7 vs. control MEFs to  CDK2 inhibition (P=0.008 by two-tailed unpaired student's t-test). Effect of a pan CDK inhibitor was near significance (P=0.07). Bars represent mean ±SD, n=3 independent MEFs.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "C. Left, representative flow cytometric analysis with  7-AAD  and AnnexinV, showing a significant decrease in apoptosis in  Rb∆K7 MEFs relative to control. Right, significant differences in average percentage of live (7-AAD-:AnnexinV-) vs. apoptotic (7-AAD+:AnnexinV+) cells. Bars represent mean ±SD; P value calculated by two-tailed unpaired student's t-test; n=3 independent MEFs.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "F-I. Delayed  hair re-growth in eight-month old Rb∆K7 mice two weeks post hair  plucking (F). (G) Abnormal skin histology in Rb∆K7 mice relative to control. FCL, subcutaneous fat cell layer, T,  telogen; A,  anagen. (H-I) Representative  immunostaining for  keratin 14 and PCNA showing reduced expression in  Rb∆K7 hair follicles vs controls. Scale bar, 50 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "J. Hyperglycemia  in Rb∆K7 but not Rb∆K4 mice. Blood glucose in 10-12-month old fasting Rb∆K7 (left, n=11) or 18-month old fasting Rb∆K4 (right, n=15) mice versus control littermates (n=6 and n=8, respectively). Mean ±SD; P values by two-tailed unpaired student's t-test.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "B.  Glucose tolerance Test  (GTT) demonstrating progressive defect in clearance of blood glucose in Rb∆K7 mice. 6-7 week (left) or 6 month (right) old fasting  Rb∆K7 mice and control  littermates (n=5-6 each per group) were injected with  glucose, and blood glucose was determined at indicated intervals. Error bars represent SD.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "F. Loss of  pancreatic islet area in Rb∆K7 mice correlates with reduced proliferation and H3K36me3 histone marks, but not with increased cell death. TUNEL analysis showing apoptosis in 10 day-old Rb∆K7 islets  is even lower than in control littermates. Arrow points to a rare  apoptotic  cell in control islet. Serine800/804 phosphorylation of pRb in β-cells from 10 day-old control but not Rb∆K7 islets with a Ser-to-Ala substitution at this site. BrdU incorporation and  PH3 staining showing reduced S-phase and mitotic cells, respectively, in 2- and 3-week old Rb∆K7 vs control islets. Reduced H3K36me3 staining in  pancreatic islets from 3-week old Rb∆K7 mice  compared to control littermates (n>3 for each experiment). Scale bar, 100 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "H. Reduced ability of  Rb∆K7 β-cell  to re-enter the cell cycle in response to pregnancy (top) or mitogenic (bottom) signals. Top, cell proliferation in P14.5 pregnant  Rb∆K7 islet β-cell  vs. control was determined by double  immunostaining with BrdU  and insulin  (left); quantification (right). Results were normalized for the number of BrdU/Insulin positive cells in control islets. An independent experiment using ki67 to quantify cell cycle re-entry top. Bottom, cell proliferation in Rb∆K7 β-cell vs. control  islets following  Exendin4  treatment was determined by  immunostaining for  Ki67; results were normalized for the number of positive cells in control islets. Mean ±SD, P values by two-tailed unpaired student's t-test. Scale bar, 100 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "I. Representative immunostaining showing induction of PDX1 (islet), SOX9 (pancreatic epithelium) and MCM4 (islet) expression  in Rb∆K7 vs control mice. Scale bar, 100 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "D. Representative image of a  pancreatic islet  from a 9-month old  Rb∆K7 mouse immunestained for the SASP marker IL-6 (red) and  insulin (green). DAPI was used to stain nuclei (blue). Arrows point to IL-6+,  insulin+  pancreatic β-cells. Scale bar, 20 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "E. Representative  immunostaining for the DDR marker γ-H2A  in islets from 3-week old Rb∆K7 and control  mice (left); statistical analysis (right; n=5 each). Arrows point to pancreatic γ-H2A-positive Rb∆K7 islet cells. Error bars represent SD; P value calculated by one-way ANOVA, Tukey's multiple comparisons test. Scale bar, 100 μm.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "H. Vitamin C diet increases 5hmC  expression and improves  β-cell  morphology and islet size in  Rb∆K7 mice. Scale bar, 100 μm. I. Vitamin C diet reduces the difference in γ−H2A+ β-cells  in  Rb∆K7 vs control pancreatic islets relative to regular diet by 3.74 folds. Bars indicate mean ±SD. Adjusted P values by one-way ANOVA, Tukey's multiple comparisons test. J. Vitamin C diet increases  pancreatic islet cell cycle  re-entry during pregnancy of Rb∆K7 mice relative to control pregnant mice (no statistical difference, n.s.) or relative to pregnant  Rb∆K7 vs control mice fed on regular diet (P<0.0001) by 3.8 folds. Bars represent mean ±SD. Adjusted P values by one-way ANOVA, Tukey's multiple comparisons test.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "B. Left, top, effect of retrovirus-mediated transduction of under-phosphorylated Rb∆K11 (rRb∆K11) on   Rb-deficient mammary tumor cell proliferation as determined by  MTT  assay (n=4-5 technical replicates). Left, bottom, quantification of SA-βGAL in rRb∆K11-transduced cells. Bars represent mean ±SD; P value calculated by two-tailed unpaired student's t-test. Right, representative images of SA-βGAL staining showing robust senescence (arrows) in rRb∆K11-transduced cells. Original magnification: 200x.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "F. Vitamin C  reduces cellular senescence induced by  retroviral-mediated over-expression of Rb∆K11. Top - images of SA-βGAL staining in human diploid cells, IMR90, transduced with control or rRb∆K11 virus with or without vitamin C added at the time of infection. Arrows point to  SA-βGAL-positive cells. Bottom left, quantification of SA-βGAL staining (bars represent mean ±SEM; n=4 biological replicates). P values by one-way ANOVA, Tukey's multiple comparisons test. Bottom right, dot-blot  analysis with antibody for 5hmC on DNA extracted from  IMR90 cells treated or not with vitamin C. Original magnification: 200x.",
    "ncbi_link": "Rb: 5925"
  },
  {
    "caption": "B Western blot  analysis of lysates of HEK293  cells 72 hours post-transfection with the various F8  variants. Neg, non-transfected cells.",
    "ncbi_link": "F8: 2157"
  },
  {
    "caption": "A  Western blot  (WB) of protein lysates of HEK293  cells 72 hours post-transfection (n=3; biological replicates) with either Npu inteins   or Heterologous (N-intein DnaB   + C-intein DnaE) split-inteins. I + II, N6 split-intein  proteins; I+II (Het.), heterologous split-intein  proteins; I, 5'N6 coding sequence (CDS)-N-DnaE  protein; I (N-int  B), 5'N6 CDS-N-DnaB. II, C-DnaE-3'N6 CDS protein. Excised inteins  (∼12kDa) are present only in the down part of the blot  when I + II (Npu inteins) are provided. Arrows indicate the full-length N6 protein, single halves and excised inteins.",
    "ncbi_link": "DnaB: 
DnaE: "
  },
  {
    "caption": "A Western blot  (WB) of protein lysates of HEK293  cells 72 hpt with the AAV-N6  split- intein  plasmids and with the codon-optimised set. I + II, N6   split-intein  proteins; I, 5' N6 CDS-N-DnaE  protein; II, C-DnaE-3'N6 CDS protein. (n=3; biological replicates). Arrows indicate the full-length N6 protein, excised inteins and both single halves. Codop: codon-optimised.",
    "ncbi_link": "DnaE: "
  },
  {
    "caption": "C Chromogenic assay performed on the medium from transfected cells to measure F8  activity levels reported as International Units/deciliter (IU/dl) (n=3; biological replicates).Data are presented as mean ±SEM. Significant differences between groups were assessed using Kruskal-Wallis test p value = 0.027. *indicates the significant difference between the I+II (N6 split-intein) and the II (C-DnaE-3'N6 CDS) groups: p value ≤ 0.05. **indicates the significant difference between the Codop I+II and the I (5' N6 CDS-N-DnaE) codop groups: p value ≤ 0.01. **indicates the significant difference between the Codop I+II and the II (C-DnaE-3'N6 CDS) codop groups: p value ≤ 0.01.",
    "ncbi_link": "DnaE: "
  },
  {
    "caption": "A Bisulfite DNA methylation sequencing of the Athila6ATE transcriptional start site (TSS) in genotypes with silenced TEs (left of the dashed line) or transcriptionally active TEs (right of the dashed line). Methylation in the CG (red), CHG (blue) and CHH (green) sequence contexts are shown (H = C, T, or A). Error bars represent Wilson score interval 95% confidence limits. For multiple statistical tests, one‐way ANOVA was performed using Tukey's multiple comparison test. ns, not significant.",
    "ncbi_link": "Athila6A: "
  },
  {
    "caption": "B The reads‐per‐million‐(RPM)‐normalized accumulation of Athila6ATE siRNAs from TE‐silenced epigenomes (left) and ddm1TE‐active epigenomes (right). Inset line graphs reflecting the same values are shown for select genotypes. All line graphs have the same y‐axis scale and are shown for increased resolution in genotypes with low siRNA levels.",
    "ncbi_link": "Athila6A: 
ddm1: 836808"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.A A representative microRNA, miR158B. The location of miR158B from this locus is shown in orange.",
    "ncbi_link": "miR158B: 6240876"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.B The SimpleHat2 non‐autonomous TE targeted by Pol IV‐RdDM.C The RDR6‐RdDM target locus TAS3a.",
    "ncbi_link": "Pol IV: 
SimpleHat2: 
RDR6: 824112
TAS3a: 3768766"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.D The Athila6A consensus element in the wt Col epigenome.E The same Athila6A consensus element as in (D) upon transcriptional activation in the ddm1 epigenome.",
    "ncbi_link": "Athila6A: 
ddm1: 836808"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.F The total small RNAs produced in the wt Col TE‐silenced epigenome.G The total small RNAs in ddm1 mutants.",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.H Bisulfite sequencing of different regions of the Athila6A element. Error bars represent Wilson score interval 95% confidence limits. Differences in the methylation status were analyzed with a two‐tailed unpaired Student's t‐test.",
    "ncbi_link": "Athila6A: "
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.I A second biological replicate of the FLAG‐AGO6‐IP and no‐antigen control followed by deep sequencing shown for the Athila6A consensus element in ddm1 mutants. The transcriptional start sites of the LTR TSS‐ and IR‐driven transcripts are shown.",
    "ncbi_link": "Athila6A: 
ddm1: 836808"
  },
  {
    "caption": "AGO6 relative enrichment of small RNAs (solid lines) and total small RNAs (dashed lines) are shown for each small RNA size class (21, 22 and 24nt) at four genomic loci.J Analysis of the first base of AGO6‐enriched siRNAs from the wt Col TE‐silenced epigenome (left) and the ddm1 TE‐transcriptionally active epigenome (right).",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "B H3Ac control ChIP from the same chromatin used in the AGO6‐IP for the At1g08200 constitutively expressed gene and the Athila6A TSS. Enrichment of H3Ac at the Athila6A TSS is increased upon transcriptional activation in ddm1 mutants, while enrichment of H3Ac at the gene At1g08200 is consistently high in both wt Col and ddm1. Data are represented as mean ± SD of six biological replicates for each genotype.",
    "ncbi_link": "Athila6A: 
At1g08200: 837341
ddm1: 836808"
  },
  {
    "caption": "C-E AGO6‐ChIP qPCR analysis of (C) the gene At1g08200 and the Pol IV‐RdDM target SimpleHat2, (D) the Athila6A TSS in wt Col TE‐silenced epigenomes (left) and ddm1 TE‐active epigenomes (right) and (E) TAS3a. ChIP signals in (D) are normalized to the ago6 or ddm1 ago6 no‐antigen controls. ChIP signals in (C) and (E) are normalized to the ago6 no‐antigen control. In (C-E), each biological replicate data point is shown as a gray dot. The data are represented as mean ± SD. For multiple statistical tests, one‐way ANOVA was performed using Tukey's multiple comparison test.",
    "ncbi_link": "Athila6A: 
Pol IV: 
SimpleHat2: 
ago6: 817856
At1g08200: 837341
ddm1: 836808
TAS3a: 3768766"
  },
  {
    "caption": "F ChIP qPCR analysis of the FLAG‐tagged POL V protein in wt Col and ddm1. ChIP signals are normalized to the wt Col no‐antigen control.",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "A AGO6 enrichment and depletion of 21-22nt siRNAs for the entire genome in 100‐bp tiles for both wt Col and ddm1. Tiles were categorized by annotation feature.",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "B Of the tiles in (A) in both wt Col and ddm1, we determined the number of tiles with ≥ 2‐fold CHH methylation dependent on RDR6.",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "C Distribution of AGO6 enrichment across TEs (solid lines) and genes (dashed lines) for different sizes of small RNAs in either the wt Col TE‐silenced epigenome or the ddm1 TE‐transcriptionally active epigenome. Dashed lines have the same color codes as the solid lines. 'Start' and 'Stop' represent the edges of the TE and the transcriptional start and stop sites of the genes.",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "D-G Heatmaps of AGO6 enrichment of TE siRNA size classes in wt Col and ddm1 epigenomes. Analyzed were (D) the position of the TE on a chromosome and TE size, (E) the copy number of the TE, (F) the TE type and (G) the TE family name. The color of the TE family name in (G) corresponds to the TE type in (F).",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "A Bisulfite sequencing of the Athila6A TSS in juvenile leaf tissue.",
    "ncbi_link": "Athila6A: "
  },
  {
    "caption": "B qRT-PCR analysis of Athila6A gag/pol steady‐state mRNA transcript levels in inflorescence and leaf tissue.",
    "ncbi_link": "Athila6A: "
  },
  {
    "caption": "C qRT-PCR analysis of AGO6 and AGO4 mRNA transcript levels in inflorescence and juvenile leaf tissue.",
    "ncbi_link": "AGO4: 817246
AGO6: 817856"
  },
  {
    "caption": "E, F Side view of an inflorescence with (E) or without (F) the AGO6‐GFP transgene.G, H Top‐down view of an inflorescence with (G) or without (H) the AGO6‐GFP transgene.",
    "ncbi_link": "AGO6: 817856"
  },
  {
    "caption": "K CHH methylation levels of the RDR6‐RdDM targets TAS3a and Athila6A TSS in whole‐inflorescence‐tissue samples compared to dissected young buds corresponding to floral stages 6-8.",
    "ncbi_link": "Athila6A: 
RDR6: 824112
TAS3a: 3768766"
  },
  {
    "caption": "A. Spike-binding  antibodies in serum. Binding  by antibodies of classes M, G, and A is detected with secondary antibodies conjugated to different fluorochromes, and the results are shown on the left, middle, and right plots, respectively. Binding  (geometric mean fluorescence intensity - GMFI- of corresponding secondary antibody) to TE  cells expressing  SARS-CoV-2 spike protein is plotted on the vertical axis, and binding to untransfected cells on the horizontal axis. Each point represents a value from one donor. Samples from donors with no known exposure to  SARS-CoV-2 antigens (n = 86) are plotted with blue circles, recently infected donors (n = 34) with red circles, and vaccinated  donors (n = 14) with green diamonds. Red circles with black triangles correspond to donors from whose  B cells monoclonal antibodies were isolated (n = 5, P values are derived from a two-way analysis of variance followed by Tukey's test to compare the specific binding, i.e., (binding  to spike-expressing cells)/(binding  to untransfected cells) between conditions (convalescent  or vaccinated  against unexposed) within each antibody class. The experiment was independently repeated three times, and results shown come from the third replicate.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "D. Comparison of spike-specific IgM, as measured by  flow cytometry or ELISA. The left two \"FC\" are the results of flow cytometry, and the left verical axis shows the ratio of serum IgM binding  to spike-expressing cells, vs binding  to non-expressing control cells, as plottted in A. The right two columns show spike-RBD-specific IgM  as measured by an IgM-capture ELISA, and the right vertical axis shows the optical densities (OD). P values are calculated by two-way analysis of variance, followed by Sidak's multiple comparisons test. The entire experiment was repeated three times, and the data shown are derived from the third replicate.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "Phenotypes  of blood B cells. B cells from 15 ml of  peripheral blood from each of three convalescent donors were isolated by negative selection with magnetic beads, exposed to adherent cells expressing spike-mCherry  for 3 hours, then retrieved and labeled with fluorescent antibodies and measured by flow cytometry. (A) UMAP algorithm (5000 randomly selected cells/sample) was used to depict the major B cell subsets clustered according to marker expression.",
    "ncbi_link": "mCherry: 
spike: 43740568"
  },
  {
    "caption": "Phenotypes  of blood B cells. B cells from 15 ml of  peripheral blood  from each of three convalescent donors were isolated by negative selection with magnetic beads, exposed to adherent cells expressing spike-mCherry  for 3 hours, then retrieved and labeled with fluorescent antibodies and measured by flow cytometry. FlowSOM-based B cell  subpopulations are overlaid as a color dimension, and the colors of the clusters are shown on the left of heatmap (B). B. Heatmap showing mean population expression  levels of markers used for UMAP visualization and FlowSOM-clustering. Colors shown in the legend on the left are also used in the UMAP representation in (A).",
    "ncbi_link": "mCherry: 
spike: 43740568"
  },
  {
    "caption": "Phenotypes  of blood B cells.  B cells  from 15 ml of  peripheral blood  from each of three convalescent donors were isolated by negative selection with magnetic beads, exposed to adherent cells expressing spike-mCherry  for 3 hours, then retrieved and labeled with fluorescent antibodies and measured by flow cytometry. C. Gating strategy to define CD69-high, mCherry-high, spike-capturing B cells (i.e., membrane antigen capture activated cells, MACAC, red box). Dot plot shows CD69  and mCherry fluorescence for  B cells from one of three donors gated by forward and side scatter, and negative for the dye used to mark the antigen donor cells.",
    "ncbi_link": "mCherry: 
spike: 43740568"
  },
  {
    "caption": "Phenotypes  of blood B cells. B cells from 15 ml of  peripheral blood  from each of three convalescent donors were isolated by negative selection with magnetic beads, exposed to adherent cells expressing spike-mCherry  for 3 hours, then retrieved and labeled with fluorescent antibodies and measured by  flow cytometry. D. Relative fractions of different B cell subpopulations, from three donors, as shown in A-B, in all B cells compared to within MACAC B cells. P values are based on two-tailed t-tests between the groups. Correlation coefficients (r) were calculated from the z-statistic of the Wilcoxon-Mann-Whitney test. A black horizontal line represents the median. Boxplots represent the interquartile range (IQR). Whiskers extend to the farthest data point within a maximum of 1.5× IQR. Every point represents one donor.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "E. Gating strategy in MACAC sorting. Single cells are selected based on scatter, antigen-expressing TE spike-mCherry  cells excluded on Cell Trace Violet label, and the spike-capturing (mCherry-high), activated (CD69-high) B cells (population labeled \"MACAC\" in red on the right-most plot) are sorted. The middle plot shows B cells that did not adhere to the TE-spike-cherry  antigen-expressing cells (putatively antigen-irrelevant), and the right plot those that did (putatively antigen-recognizing). Plots show data from one of five convalescent donors Cells in the MACAC  gate were singly distributed into wells of 384-well plates and cultured for 9 days with  IL-21 and CD40L, and then the single well culture supernatants were screened for anti-spike  antibody binding  and virus neutralization as described below. F. Results of single well supernatant screening for antibody binding  to SARS-CoV-2 spike  protein. Results from 3266 wells from 5 donors are shown for IgM  (left), IgG (middle), and IgA  (right).",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "E. Flow cytometric  determination of antibody-dependent complement  deposition on cells. Cells expressing SARS-CoV-2 spike  protein and untransfected control cells were incubated with various concentrations of antibody in the presence of fresh human serum  (from a SARS-CoV-2  unexposed donor). Activation of the complement  cascade was measured by  flow cytometric assessment of complement component C3b  deposition on the surface of the cells. Results for the 3 IgM, (black), 11 IgG, (blue), and 6 IgA  antibodies (red) are shown. P values were calculated by two-way analysis of variance, followed by Tukey's test.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "A. The effect of competition on concentration versus binding  curves of three spike-specific, class-switched antibodies. Antibodies were expressed either as IgM, as originally isolated (black symbols and lines), or artificially switched to IgG1  (blue lines and symbols). For each antibody, identified by name at the top of each plot, the binding  of the antibody alone (\"alone\", open symbols), or the  competitive binding  of the antibody in a mixture of IgM  and IgG1  (\"compet.\", filled symbols) is shown. In the competition scenario, each of the two classes of the antibody were added together at the concentration shown on the horizontal axis. The vertical axis shows the ratio of geometric mean fluorescence of human IgM, or IgG  on spike-expressing cells divided by the corresponding signal on spike-non-expressing control cells. Each point shows the mean of 3 values from three independent experiments. Error bars show standard error. P value was calculated by comparing the area under the curve of each antibody class in the \"alone\" condition with the binding  of the \"competition\" condition by paired, two-tailed t-test.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "C. Flow-cytometric epitope binning of monoclonal IgM, utilizing competitive displacement of IgG  by IgM  with identical variable region Cells expressing SARS-CoV-2 spike  protein and untransfected control cells were incubated with each of 3 neutralizing IgM  antibodies artificially switched  to IgG1, either alone, or mixed with one of the 3 antibodies expressed as IgM. The binding  of each IgG1  alone is shown in the last column of the heatmap, and in competition with each other IgM  in columns 1-3. Color shade represents the specific IgG binding  (ratio of GMFI on TE spike-mCherry  cells to TE 0 cells). Values are mean GMFI ratios from three independent experiments. When IgM binds  the same epitope as the IgG  (automatically the case when the source antibody is the same), the IgM  will displace the IgG, resulting in a reduction in the IgG  signal. Asterisks mark those combinations of antibodies with a statistically significant decrease in binding  of the IgG1  in the presence of IgM, compared to the IgG  alone across 3 independent experiments, (* p<0.05, two-way analysis of variance, followed by Tukey's test).",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "(A) RFP-ATG8g-labeled autophagosomes  were quantified from plants   syringe infected with mock or Xcv ΔxopQ (oD600=0.2) at 2 dpi in the presence or absence of ConA  (bars = 20 μm). Puncta were calculated from z-stacks (15) of n=6 individuals using ImageJ. Central band of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Different letters indicate statistically different groups (P < 0.05) as determined by one-way ANOVA. The experiment was repeated twice with similar results.",
    "ncbi_link": "xopQ: "
  },
  {
    "caption": "(B) Immunoblot  analysis of NBR1  and ATG8  protein levels in Xcv ΔxopQ or mock infected  N. benthamiana  plants at 1 and 2dpi. Agrobacterium-mediated transient expression of AIMp-RFP  serves as a control for autophagy   suppression.  Ponceau Staining (PS) served as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "RFP: 
xopQ: 
AIMp: 9461793"
  },
  {
    "caption": "(C) RLUC-ATG8a  or RLUC-NBR1  constructs were coexpressed with internal control FLUC  in N. benthamiana. Xcv ΔxopQ was co-infiltrated with Agrobacteria containing the luciferase  reporter constructs. Coexpression of RFP-AIMp   serves as a control for autophagy  inhibition. Expression of the latter was confirmed with western blot  (inset). Renilla  (RLUC) and Firefly  (FLUC) luciferase  activities were simultaneously measured in leaf  extracts at 48 h post- infiltration using the  dual-luciferase  system  (n=4). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (***P<0.001) was revealed by Student's t-test. The experiment was repeated more than 3 times with similar results.",
    "ncbi_link": "FLUC: 
luciferase: 
RLUC: 
xopQ: 
ATG8a: 828287
NBR1: 828571"
  },
  {
    "caption": "(D)  RT-qPCR analysis of NbATG8-1.1/1.2, NbATG8-2.1/2.2 and NbJoka2 transcript levels upon challenge of N. benthamiana plants with  Xcv ΔxopQ for 1 and 2 dpi compared to mock infected plants. Values represent expression relative to mock control of respective time point  and were normalized to actin. Values are biological replicates (n=4). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (*P < 0.05, **P < 0.01, *** P < 0.001) was revealed by Student's t-test.",
    "ncbi_link": "actin: 
ATG8: 
Joka2: 
xopQ: "
  },
  {
    "caption": "(E) Bacterial density in leaves  of N. benthamiana infected with Xcv in the presence or absence autophagy suppressor AIMp-RFP. Leaves were syringe-infiltrated with OD600 = 0.0004, and colony-forming units  were counted at 6 dpi. Compared to empty vector control (EV), AIMp  expressing plants (n=6) harbour significantly more bacteria. Bacterial growth was repeated with the same result in 12 plants over two independent experiments. Red and yellow data points indicate independent repeats of the experiment. Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (***P < 0.001) was revealed by Student's t-test. Expression of RFP-AIMp  was verified at 6 dpi with an anti-RFP blot  (inset).",
    "ncbi_link": "RFP: 
AIMp: 9461793"
  },
  {
    "caption": "(A) RLUC-ATG8a  or RLUC-NBR1 constructs were coexpressed with internal control FLUC  in N. benthamiana. XopL  or GFP constructs were co-infiltrated. RLUC  and FLUC  signals were simultaneously measured in leaf  extracts at 48 h post- infiltration using the dual-luciferase  system. Values represent the ratio of RLUC-ATG8a  and FLUC  activities to the mean of control (n=4). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (P < 0.01) was shown by Student's t-test. The experiment was repeated more than 3 times by with similar results.",
    "ncbi_link": "FLUC: 
GFP: 
RLUC: 
XopL: 
ATG8a: 828287
NBR1: 828571"
  },
  {
    "caption": "(B) Immunoblot  analysis of NBR1  and ATG8  protein levels in  N. benthamiana  plants transiently expressing GFP-XopL or GFP control at 2dpi verified with an anti-GFP  antibody (same blot was split for visualization purpose).  Ponceau Staining (PS) served as a loading control. The experiment was repeated at least three times with similar results.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(C) Immunoblot  analysis of ATG8  protein levels in  N. benthamiana plants transiently expressing XopL  or GUS  control at 2dpi after ConA  or DMSO treatment. Expression  of GFP-XopL  was verified with an anti-GFP antibody, while expression  of GUS-HA  was confirmed with an anti-HA  antibody. Ponceau Staining (PS) served as a loading control. The experiment was repeated twice with similar results.",
    "ncbi_link": "XopL: 
GUS: 946149"
  },
  {
    "caption": "(D) GFP-ATG8g-labeled autophagosomes  were quantified from plants infected with Xcv  or Xcv ΔxopL at 2 dpi in the presence or absence of ConA. Puncta were calculated from z-stacks (15) of n=12 individuals using ImageJ. Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (** P < 0.01, *** P < 0.001) was determined by one way ANOVA. The experiment was repeated twice with similar results.",
    "ncbi_link": "xopL: "
  },
  {
    "caption": "(E) Immunoblot  analysis of NBR1  and ATG8  protein levels in Xcv ΔxopQ, Xcv  ΔxopQ ΔxopL or mock infected N. benthamiana plants at 2dpi. Ponceau Staining (PS) served as a loading control. The experiment was repeated twice with similar results.",
    "ncbi_link": "xopL: 
xopQ: "
  },
  {
    "caption": "(F) RLUC-ATG8a  or RLUC-NBR1  constructs were coexpressed with internal control FLUC  in N. benthamiana. Xcv ΔxopQ and Xcv ΔxopQ  ΔxopL were co-infiltrated with Agrobacteria  containing the respective constructs. RLUC  and FLUC  activities were simultaneously measured in leaf  extracts at 48 h post- infiltration using the  dual-luciferase  system. Values represent the ratio of RLUC-ATG8a  and FLUC  activities (n=4). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance comparing Xcv ΔxopQ and Xcv ΔxopQ ΔxopL values (***P < 0.001) was revealed by Student's t-test. The experiment was repeated 3 times with similar results.",
    "ncbi_link": "FLUC: 
RLUC: 
xopL: 
xopQ: 
ATG8a: 828287
NBR1: 828571"
  },
  {
    "caption": "(A) Interaction  of XopL  with SH3P2  in yeast two-hybrid assays. XopL  fused to the GAL4  DNA-binding   domain was expressed in combination with SH3P2  fused to the GAL4  activation domain (AD) in  yeast strain Y190. Cells were grown on  selective media before a LacZ  filter assay was performed. pSV40/p53  served as positive control, while the empty AD or BD vector served as negative control.  NtSH3P2 = Nicotiana tabacum SH3P2. -LT = yeast   growth on medium without Leu  and Trp, -HLT = yeast   growth on medium lacking His, Leu, and Trp, indicating expression of the HIS3  reporter gene. LacZ, activity of the lacZ  reporter gene.",
    "ncbi_link": "HIS3: 
LacZ: 
lacZ: 
GAL4: 855828
p53: 716170"
  },
  {
    "caption": "(B) Coimmunoprecipitation  of GFP-XopL  with AtSH3P2-HA. GFP-XopL  or GFP  were transiently coexpressed with AtSH3P2-HA   in leaves  of N. benthamiana. After 48 h, total proteins (Input) were subjected to immunoprecipitation  (IP) with GFP-Trap beads, followed by immunoblot  analysis using either anti-GFP  or anti-HA  antibodies. GFP blot  was split for visualization purpose. AtSH3P2 = Arabidopsis thaliana SH3P2. Two repetitions with similar results have been conducted.",
    "ncbi_link": "GFP: 
HA: 
XopL: 
SH3P2: 829618"
  },
  {
    "caption": "(E) Total proteins were extracted 48 hpi with  A. tumefaciens harboring the respective GFP-XopL, HA-XopL  and SH3P2-GFP expression  constructs. SH3P2-GFP  protein levels (lower band) were detected using an anti-GFP antibody. Expression   of the XopL was verified using an anti-HA  or anti-GFP  antibody. Expression  of GUS-HA  served as a control. Ponceau S staining serves as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
HA: 
XopL: 
SH3P2: 829618"
  },
  {
    "caption": "(F) Growth  of Xcv and Xcv  ΔxopL strains in  roq1 N. benthamiana plants silenced for SH3P2  (pTRV2-SH3P2) compared to control plants (pTRV2). Leaves  were dip-inoculated with a bacteria suspension at OD600 = 0.2 and bacteria were quantified at 3 and 6 dpi. Experimental repeats are indicated by data points in red (n=8) and yellow (n=6) data points. Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Different letters indicate statistically significant differences (P < 0.05) as determined by one-way ANOVA.",
    "ncbi_link": "xopL: 
SH3P2: 107790934"
  },
  {
    "caption": "(A) SH3P2-GFP   was transiently coexpressed together with GUS-HA  and GFP-XopL  in N. benthamiana using agroinfiltration. At 42 hpi, 200 μM MG132 was infiltrated into  A. tumefaciens-inoculated leaves, and leaf  material was collected 48 hpi. Expression   of SH3P2-GFP  (lower band) and GFP-XopL  (upper band) was detected using an anti-GFP  antibody. GUS-HA expression   was confirmed with an anti-HA  antibody.  Ponceau S staining serves as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
HA: 
XopL: 
SH3P2: 829618
GUS: 946149"
  },
  {
    "caption": "(C) SH3P2-GFP was transiently coexpressed together with GFP, GFP-XopL  and GFP-XopL ΔE3 in N. benthamiana using agroinfiltration. GFP protein levels were detected with an anti-GFP  antibody. Ponceau S staining serves as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(D) Immunoblot  analysis of ATG8  protein levels in N. benthamiana plants transiently expressing GFP-XopL, GFP-XopL ΔE3 or GFP  control at 2dpi. Expression of binary constructs was verified with an anti-GFP  antibody. GFP blot  was split for visualization purpose. Ponceau Staining (PS) served as a loading control. The experiment was repeated twice with similar results.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(E) RLUC-ATG8a  constructs were coexpressed with internal control FLUC  in N. benthamiana. GFP-XopL, GFP-XopL ΔE3 or GFP  control were co-infiltrated together with RLUC/FLUC  mixture. Renilla  and Firefly luciferase  activities were simultaneously measured in leaf  extracts at 48 hpi using the  dual-luciferase system. Values represent the ratio of RLUC-ATG8a  and FLUC  activities (n=4). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Statistical significance (* P < 0.5, ** P < 0.01) was revealed by Student's t-test. The experiment was repeated 3 times.",
    "ncbi_link": "FLUC: 
GFP: 
luciferase: 
RLUC: 
XopL: 
ATG8a: 828287"
  },
  {
    "caption": "(A) GFP-XopL was coexpressed with GFP  or AIMp-RFP. Proteins were separated by SDS-PAGE  and detected by immunoblotting  using the indicated antibodies. GFP blot  was split for visualization purpose. Ponceau Staining (PS) served as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
RFP: 
XopL: 
AIMp: 9461793"
  },
  {
    "caption": "(C)  FRET FLIM  measurements of GFP-Joka2  and RFP-XopL  in  N. benthamiana leaves. The freeRFP construct served as a negative control and RFP-ATG8E  (n = 9) as a positive control. Scattered points show individual data points, color indicates biological repeats. The lifetime  (in ns) of GFP-Joka2  (donor, n = 41) was significantly reduced in the presence of RFP-XopL  (n = 40) but not in the presence of freeRFP (n = 35). Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Significant differences were calculated using Wilcoxon rank sum test, with significantly different groups denoted by different letters. The experiment was repeated three times with similar results.",
    "ncbi_link": "RFP: 
XopL: 
ATG8E: 819125"
  },
  {
    "caption": "(D) Immunoprecipitation  (IP) of GFP-XopL  reveals association with NBR1. Immunoblots  of input and IP  samples from N. benthamiana plants transiently expressing GFP or GFP-XopL  were probed with anti-GFP  and anti-NBR1 antibodies. GFP blot  was split for visualization purpose.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(E) Immunoprecipitation  (IP) of GFP-XopL  and GFP-XopL ΔE3 reveals association with NBR1. Immunoblots  of input and IP  samples from  N. benthamiana  plants transiently expressing GFP, GFP-XopL  and GFP-XopL ΔE3 were probed with anti-GFP  and anti-NBR1  antibodies. GFP blot  was split for visualization purpose.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(F) GFP-XopL  was transiently expressed in pTRV2, pTRV2-Joka2  and N. benthamiana  WT plants. Expression   of binary constructs was verified with an anti-GFP  antibody. Joka2  silencing was verified using an anti-NBR1  antibody. Ponceau Staining (PS) served as a loading control. The experiment was repeated twice with similar results.",
    "ncbi_link": "Joka2: "
  },
  {
    "caption": "(G) Growth  of Xcv ΔxopQ in N. benthamiana  plants silenced for Joka2  (pTRV2-Joka2) compared to control plants (pTRV2). Leaves  were dip-inoculated with a bacteria suspension at OD600 = 0.2. and bacteria were quantified at 3 and 6 dpi. Red, blue, and green data points represent repeats of the experiments. Middle horizontal bars of boxplots represent the median, the bottom and top represent the 25th and 75th percentiles, whiskers extend to at most 1.5 times the interquartile range. Significant differences were calculated using Student's t-test and are indicated by: **, P < 0.01. The experiment was repeated three times with similar trends.",
    "ncbi_link": "Joka2: 
xopQ: "
  },
  {
    "caption": "(H) GFP-XopL, GFP-XopL ΔE3 were transiently expressed in N. benthamiana. RFP-AIMp  was co-infiltrated to stabilize both XopL  variants. Samples were taken 48 hpi, and total proteins (Input) were subjected to immunoprecipitation  (IP) with GFP-Trap beads, followed by immunoblot  analysis of the precipitates using either anti-GFP  or anti-ubiquitin  antibodies. GFP  served as a negative control. RFP-AIMp expression was verified by an anti-RFP  antibody. GFP blot  was split for visualization purpose. Asterisk indicates the GFP-XopL  full-length protein. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
RFP: 
XopL: 
AIMp: 9461793"
  },
  {
    "caption": "(I) GFP-XopL  was transiently expressed in N. benthamiana. Samples were taken 48 hpi, and total proteins (Input) were subjected to immunoprecipitation (IP) with the ubiquitin  pan selector, followed by immunoblot analysis of the precipitates using either anti-GFP  or anti-ubiquitin  antibodies. GFP  served as a control. Asterisk indicates the GFP-XopL  full-length protein. GFP blot  was split for visualization purpose. The experiment was repeated two times with similar results.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(J) Immunoblot  analysis GFP-XopL  and GFP-XopLK191A at 1 and 2 dpi using an anti-GFP  antibody. Ponceau Staining (PS) served as a loading control. The experiment was repeated three times with similar results.",
    "ncbi_link": "GFP: 
XopL: "
  },
  {
    "caption": "(K) HA-XopL  and GFP-Joka2  and its variants were transiently expressed in N. benthamiana. Samples were taken 48 hpi, and total proteins (Input) were subjected to immunoprecipitation  (IP) with GFP-Trap beads, followed by immunoblot  analysis of the precipitates using either anti-GFP, anti-ubiquitin  and anti-NBR1  antibodies. GFP  served as a control.",
    "ncbi_link": "GFP: 
HA: 
Joka2: 
XopL: "
  },
  {
    "caption": "C. MLE-12 AECs incubated with MH-S EVs infected with PR/8 influenza. Replication was quantified by RT-qPCR at 12 h post infection. Data represent mean M gene transcripts normalized to β actin from 3 independent experiments.",
    "ncbi_link": "β actin: 
M: 23308107"
  },
  {
    "caption": "E Total lung RNA was isolated from mice on day 1 post infection and virus was quantified by RT-qPCR. Data represent mean M gene transcripts from individual mice normalized to β actin from 3 independent experiments (4-5 mice per group).",
    "ncbi_link": "β actin: 
M: 23308107"
  },
  {
    "caption": "A. MLE-12 AECs co-incubated with the listed WT strains (MOI = 0.4) plus AM-EVs (grey bars, EV:cell = 1). Data represent mean M gene transcripts at 12 h post infection relative to the mean of the corresponding untreated strain (white bars), each normalized to β actin from 2-4 independent experiments per strain.",
    "ncbi_link": "β actin: 
M: 23308107"
  },
  {
    "caption": "MLE-12 cells were incubated with WT PR/8 + AM-EVs at 4 °C (to permit surface binding but not entry) for 1 h, washed, and processed for (B) RNA isolation (B) Data represent mean M gene transcripts relative to the means of the corresponding untreated condition, each normalized to β actin from 3 independent experiments.",
    "ncbi_link": "β actin: 
M: 23308107"
  },
  {
    "caption": "C. RT-qPCR analysis of relative mRNA expression of Pde10a in BAT, peri-ovarian visceral white adipose tissue (VAT) and inguinal subcutaneous white adipose tissue (SAT) of lean mice (n = 5). ** P = 0.0063 (SAT vs VAT), ** P = 0.0011 (SAT vs BAT) and ** P = 0.0037 (VAT vs BAT) using unpaired 2-tailed Student's t test.",
    "ncbi_link": "Pde10a: 23984"
  },
  {
    "caption": "E RT-qPCR analysis of relative mRNA expression of thermogenic genes in SAT, VAT and BAT after treatment of lean mice treated with MP-10 (30 mg/kg) (n=7) or vehicle control (n = 6). **** P < 0.0001 (Pgc1alpha in VAT), ** P = 0.0012 (Ucp1 in VAT), ** P = 0.0071 (Pgc1alpha in BAT) and * P = 0.0486 (Ucp1 in BAT) using unpaired 2-tailed Student's t tests.",
    "ncbi_link": "Pgc1alpha: 19017
Ucp1: 22227"
  },
  {
    "caption": "Representative fused PET/MRI images of the transverse view of the thoracic region of lean (n = 5), diet induced obese (DIO) (n = 4) and leptin deficient (ob/ob) (n = 5) mice that received the PDE10A radioligand [18F]-AQ28A. Interscapular brown adipose tissue (BAT) in each image is highlighted by the crosshairs. The mean standardized uptake (SUV) value of [18F]-AQ28A in BAT throughout the dynamic scan was calculated with associated area under the curve (AUC). * P = 0.0128 (lean vs DIO) and ** P = 0.0031 (lean vs ob/ob) using unpaired 2-tailed Student's t test.",
    "ncbi_link": "ob: 16846"
  },
  {
    "caption": "G. RT-qPCR analysis of relative mRNA expression of candidate genes in inguinal subcutaneous white adipose tissue (SAT), periovarian visceral white adipose tissue (VAT) and interscapularbrown adipose tissue (BAT) (n = 8 per group) *** P = 0.0004 (Pgc1alpha VAT), ** P = 0.0036 (Ucp1 VAT), ** P = 0.0068 (Cidea VAT), * P = 0.0411 (Tmem26 VAT) and ** P = 0.0070 (Pgc1alpha BAT) using unpaired 2-tailed Student's t tests.",
    "ncbi_link": "Cidea: 12683
Pgc1alpha: 19017
Tmem26: 327766
Ucp1: 22227"
  },
  {
    "caption": "A. RT-qPCR analysis of relative mRNA expression of thermogenic genes in cultured primary human brown adipocytes in response to chronic treatments (8 hours) with DMSO (control), MP-10 (1nM and 100nM), cyclic AMP (cAMP - 10µM), cyclic GMP (cGMP - 10µM) and cAMP + cGMP (cA + cG - 10µM (n = 4 separate cultures). * P = 0.0278 vs (100nM MP-10 vs control; Pgc1alpha), **P = 0.0097 (10µM cA + cG vs control; Pgc1alpha), ** P = 0.0063 (1nM MP-10 vs control; Ucp1), **** P < 0.0001 (100nM MP-10 vs control; Ucp1), ## P = 0.0017 (1nM MP-10 vs 100nM MP-10; Ucp1), §§§§ P < 0.0001 (10µM cAMP vs 100nM MP-10; Ucp1), §§§§ P < 0.0001 (10µM cGMP vs 100nM MP-10; Ucp1), §§§§ P < 0.0001 (10µM cA + cG vs 100nM MP-10; Ucp1), * P = 0.0112 vs (100nM MP-10 vs control; Cidea), *** P = 0.0007 (1nM MP-10 vs control; Dio2), **** P < 0.0001 (100nM MP-10 vs control; Dio2), # P = 0.0267 (1nM MP-10 vs 10µM cAMP; Dio2), §§§ P = 0.0001 (10µM cAMP vs 100nM MP-10; Dio2), §§§ P = 0.0007 (10µM cGMP vs 100nM MP-10; Dio2), * P = 0.0232 (10µM cA + cG vs control; Dio2) §§ P = 0.0058 (10µM cA + cG vs 100nM MP-10; Dio2), * P = 0.0416 (10µM cGMP vs control; Prdm16) and * P = 0.0105 (10µM cA + cG vs control; Prdm16) using one-way analysis of variance (ANOVA) with Tukey's post-hoc test.B. RT-qPCR analysis of relative mRNA expression of thermogenic genes in cultured primary human white adipocytes in response to chronic treatments (8 hours) with DMSO (control), MP-10 (1nM and 100nM), cyclic AMP (cAMP - 10µM), cyclic GMP (cGMP - 10µM) and cAMP + cGMP (cA + cG - 10µM (n = 4 separate cultures). * P = 0.0186 vs (1nM MP-10 vs control; Ucp1), **** P < 0.0001 (100nM MP-10 vs control; Ucp1), ## P = 0.0016 (1nM MP-10 vs 100nM MP-10; Ucp1), *** P = 0.0003 (10µM cAMP vs control; Ucp1), §§§ P = 0.0002 (10µM cGMP vs 100nM MP-10; Ucp1) and *** P = 0.0003 (cA + cG vs control; Ucp1) using one-way analysis of variance (ANOVA) with Tukey's post-hoc test.",
    "ncbi_link": "Cidea: 1149
Dio2: 1734
Pgc1alpha: 10891
Prdm16: 63976
Ucp1: 7350"
  },
  {
    "caption": "Egg chamber elongation is unaffected by reduced cell proliferation. String-shRNA expressed for 24 hours alters epithelial shape and cell number (A Chambers shown in (A) have approximately equal widths, with the cross-sectional area corresponding to developmental stage 6. Scale bars = 20 μm. Number of chambers analyzed: w1118 1.0-1.2 n=24,1.2-1.4 n=14,1.4-1.6 n=18 String-shRNA 1.0-1.2 n= 11 ,1.2-1.4 n=10,1.4-1.6 n=15. Bars represent mean and standard deviation",
    "ncbi_link": "String: 43466"
  },
  {
    "caption": "Egg chamber elongation is unaffected by reduced cell proliferation. String-shRNA expressed for 24 hours alters epithelial shape and cell numbe but not the relationship between egg chamber aspect ratio and cross-sectional area, which is quantified in (B) Number of chambers analyzed: w1118 1.0-1.2 n=24,1.2-1.4 n=14,1.4-1.6 n=18 String-shRNA 1.0-1.2 n= 11 ,1.2-1.4 n=10,1.4-1.6 n=15. Bars represent mean and standard deviation",
    "ncbi_link": "String: 43466"
  },
  {
    "caption": "C, D) Cell proliferation is necessary for normal tissue morphology Follicle cell shape regularity (C) and polygonality (D) measurements in control and String-shRNA egg chambers of different aspect ratios. These measurements were derived from at least three egg chambers from at least three flies per AR range. Bars represent mean and standard deviation. Statistical significance for cell side distributions was calculated using a chi-squared test. Number of cells used for analysis: w1118 1.0-1.2 n= 23, 1.2-1.4 n=114, 1.4-1.6 n=160; String-shRNA 1.0-1.2, n=6, 1.2-1.4 n=19, 1.4-1.6 n=17",
    "ncbi_link": "String: 43466"
  },
  {
    "caption": "Epithelial cell size and shape is affected by decreased proliferation. Cell outlines are marked with Basigin::YFP. Scale bars =­ 5 μm. Cells become more aligned with the tissue elongation axis when proliferation is stopped using String-shRNA (C). Number of cells analyzed: w1118 1.0-1.2 n= 14, 1.2-1.4 n=114, 1.4-1.6 n=160; String-shRNA 1.0-1.2, n=10, 1.2-1.4 n=19, 1.4-1.6 n=17. Statistical significance calculated using a Mann-Whitney test. Data information: Bars represent mean and standard deviation.",
    "ncbi_link": "String: 43466"
  },
  {
    "caption": "D, E) The follicular epithelium 'thins out' over the egg chamber equator when proliferation is blocked. Cartoon demonstrates the tissue cell shape observed in the follicular epithelium in control (w1118) and String-shRNA treated egg chambers. Quantification of the phenomenon shown in (D) reveals that cells are shorter over the equator than at the anterior pole in elongated egg chambers when proliferation is blocked. Statistical significance calculated using unpaired t-test with Welch's correction. Number of cells analyzed: w1118 1.0-1.2 n= 21, 1.2-1.4 n=11, 1.4-1.6 n=10; String-shRNA 1.0-1.2, n=9, 1.2-1.4 n=11, 1.4-1.6 n=13. Data information: Bars represent mean and standard deviation.",
    "ncbi_link": "String: 43466"
  },
  {
    "caption": "F) Recoil is observed when cuts are made in apical cortex with a 2-photon laser with egg chambers in saggital view. Images show cortex before and after cutting. Scale bars = 10 μm. Yellow arrows indicate edges of ablated region. G) Recoil is higher when cuts are made at the apical cortex at the equator of egg chambers, rather than at the poles. Quantification of experiment shown in (F). Statistical significance tested by Mann-Whitney test. Number of laser cuts: equator n=30, pole n=20. Data information Laser ablation experiments performed on tissue from sqhAX3, sqh::GFP flies.",
    "ncbi_link": "sqh: 31554"
  },
  {
    "caption": "H) Recoil is observed when larger cuts are made in apical cortex with a UV laser. Images show cortex before and after cutting. Red lines indicate the lines over which recoil was calculated, parallel to the axes of the egg chamber. Scale bars = 5 μm. Yellow arrows indicate edges of ablated region. I) Recoil tends to be higher towards the AP (elongation) axis compared to the the UD (rotation) axis. Graph shows the ratio of recoil speed plotted on a log2 scale in the AP versus the UD axis. Red line at x=1 indicates equal recoil in both axes. Values above 1 indicate higher recoil speeds in the AP axis lower than 1 indicate higher recoil in the UD axis. AP/UD Ratio Median = 1.242 ; Mean = 2.1. Wilcoxon Signed Rank Test to test for significance of the recoil ratio AP/UD shows that the median is significantly different from 1 to p = 0.0172. Number of cuts = 20. Bar represents median.Laser ablation experiments performed on tissue from sqhAX3, sqh::GFP flies.",
    "ncbi_link": "sqh: 31554"
  },
  {
    "caption": "C) Planar division orientation at Stage 6 correlates with tissue expansion in Fat2-shRNA and Pak-shRNA egg chambers. Mann Whitney test w1118 versus Pak shRNA p = 0.0094. Neither the Fat2-shRNA nor Pak-shRNA distributions are stastically different from random (Wilcoxon Signed Rank Test, Theoretical Mean of 45). Number of cells analyzed: w1118 n =97, Fat2-shRNA n=44, Pak-shRNA n=39. Egg chambers analyzed: w1118 n=40, Fat2-shRNA n=21, Pak-shRNA n=21",
    "ncbi_link": "Fat2: 40191
Pak: 44039"
  },
  {
    "caption": "Tissue topology is affected by disruption of Canoe, but not Mud (D) Statistical significance for cell side distributions was calculated using a chi-squared test. Number of cells analyzed: w1118 1.4-1.6 n=284; Canoe-shRNA 1.4-1.6 n=310; mud3/mud4 1.4-1.6 n=251",
    "ncbi_link": "Canoe: 40620
Mud: 44839
mud: 44839"
  },
  {
    "caption": "Tissue topology is affected by disruption of Canoe, but not Mud Representative image of a Canoe-shRNA follicle epithelium. Cell outlines are marked with Basigin::YFP. This egg chamber has no mitotic cells and AR of 1.58. Scale bars = 5 μm",
    "ncbi_link": "Canoe: 40620
Mud: 44839"
  },
  {
    "caption": "C38 and IB3-1 cells transfected with GFP-LC3 plasmid in nutrient-rich or starvation medium. (a) Top: confocal microscopy of GFP. N, nucleus. Scale bar, 10 μm. Bottom: percentage of cells containing more than five GFP-LC3 punctate dots per cell. Means ± s.d. (n = 5). Asterisk, P 0.001 versus C38 cells; analysis of variance (ANOVA).",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "(k) Number of LC3-positive dots in lung tissues from wild-type (WT) and CftrF508del mice. Means ± s.d. for lung tissues from ten mice per group. Asterisk, P 0.001 versus WT mice; ANOVA. (l) Confocal microscopy of p62 in WT and CftrF508del homozygous mice. Representative staining from at least five airway epithelial areas per mouse (n = 10 mice per group). L, lumen. Nuclei counterstained with DAPI (blue). Scale bar, 10 μm.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(g) Left: electron microscopy of HA-beclin 1-transfected IB3-1 cells shows areas enriched in autophagosomes (arrows). Scale bar, 250 nm. Right: number of autophagosomes per cell; 20 cells were counted in each experiment. Means ± s.d. for three independent experiments. Asterisk, P 0.001 versus cells transfected with the empty vector; ANOVA.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(j) Immunoblot of beclin 1 in WT and CftrF508del mice. Representative of seven mice for each group.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(k, l) CftrF508del mice (n = 3 per group) were administered intranasally with a lentiviral vector encoding beclin 1 (LV-beclin 1) or GFP (LV-GFP). (k) LC3-positive dots per mm2 of lung tissues. Means ± s.d. for lung tissues from three mice per group. (l) Confocal microscopy micrographs of p62. L, lumen. Representative stainings from at least five airway epithelial areas per mouse. Scale bar, 10 μm.",
    "ncbi_link": "beclin 1: 56208
Cftr: 12638"
  },
  {
    "caption": "(a) IB3-1 cells cultured with 250 μM cystamine or transfected with either 50 nM human TG2 siRNA or scrambled oligonucleotides. IP, immunoprecipitation; IB, immunoblot.",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "(c, d) IB3-1 cells transfected with either human TG2 siRNA or scrambled oligonucleotides followed by incubation with MG132. (c) Cells immunostained with anti-beclin 1 (green) and anti-HDAC-6 (red) antibodies. Yellow indicates co-localization. N, nucleus. Scale bar, 10 μm.",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "(c, d) IB3-1 cells transfected with either humanTG2 siRNA or scrambled oligonucleotides followed by incubation with MG132. (d) FRET analysis of beclin 1-Alexa 546 (Al546) fluorescence after HDAC6-Cy5 photobleaching. F/F0 indicates the post-bleaching/pre-bleaching fluorescence ratio of Al546/Cy5.",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "(e) IB3-1 cells were transfected with either human TG2 siRNA or scrambled oligonucleotides. Immunoblot of TG2, Ambra-1, hVps15, hVps34, Atg14L and beclin 1 in IB3-1 cells grown in starvation. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "(f) IB3-1 and C38 cells were transfected with either 1 μg of pLPCX-WT-TG or pLPCX-Cys277Ser-TG or the empty vector. Immunoblot of beclin 1. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "TG: 7052"
  },
  {
    "caption": "(g, h) IB3-1 cells were treated with cystamine or 10 mM EUK-134 or transfected with either 50 nM humanPIASy siRNA or scrambled oligonucleotides. (g) Percentage of cells containing more than five GFP-LC3 punctate dots. Means ± s.d. for three independent experiments. Asterisk, P 0.001 versus control; ANOVA.",
    "ncbi_link": "PIASy: 51588"
  },
  {
    "caption": "(g, h) IB3-1 cells were treated with cystamine or 10 mM EUK-134 or transfected with either 50 nM humanPIASy siRNA or scrambled oligonucleotides. (h) Left: electron micrographs of IB3-1 cells showing areas enriched in autophagosomes (arrows) on PIASy gene silencing, EUK-134 or cystamine. Scale bar, 100 nm. Right: number of autophagosomes per cell counted in 20 cells per experiment. Means ± s.d. for three independent experiments. Asterisk, P 0.001 versus control; ANOVA.",
    "ncbi_link": "PIASy: 51588"
  },
  {
    "caption": "(j) IB3-1 cells treated with cystamine or EUK-134 or transfected with human PIASy siRNA or scrambled oligonucleotides. Immunoblot of beclin 1 (left) and PIASy (right). Uncropped images of blots are shown in Supplementary Information, Fig. S10. The experiments were repeated three times. β-actin was used as loading control for all blots. Densitometric analysis of blots and quantitative measurement of co-localizations are shown in Supplementary Information, Fig. S9.",
    "ncbi_link": "PIASy: 51588"
  },
  {
    "caption": "(a, b) C38 cells were transfected with either 50 nM human CFTR siRNA or scrambled oligonucleotides (a, b) or cultured with CFTRinh-172 (b) in the presence or absence of cystamine (250 μM) or EUK-134 (10 mM). (a) Immunoblot of beclin 1, LC3 and p62 in C38 cells on starvation. Uncropped images of blots are shown in Supplementary Information, Fig. S10. (b) Percentage of cells containing more than five GFP-LC3 punctate dots per cell. Means ± s.d. for three independent experiments. Asterisk, P 0.001 versus scrambled oligonucleotides; circle, P 0.01 versus CFTR siRNA or CFTRinh-172; ANOVA.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(c-g) A549 cells were transfected with 1 μg of pGFP--CFTRF508del or pGFP (empty vector), in the presence or absence of 10 mM EUK-134 or 250 μM cystamine. (c) Immunoblot of TG2 and PIASy.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(c-g) A549 cells were transfected with 1 μg of pGFP--CFTRF508del or pGFP (empty vector), in the presence or absence of 10 mM EUK-134 or 250 μM cystamine.(d) FRET analysis of TG2-Alexa 546 fluorescence after SUMO-1 Cy5 photobleaching.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(c-g) A549 cells were transfected with 1 μg of pGFP--CFTRF508del or pGFP (empty vector), in the presence or absence of 10 mM EUK-134 or 250 μM cystamine.(e) Immunoblot of beclin 1 and LC3 in A549 cells after starvation. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(c-g) A549 cells were transfected with 1 μg of pGFP--CFTRF508del or pGFP (empty vector), in the presence or absence of 10 mM EUK-134 or 250 μM cystamine.(f) Percentage of cells containing more than five GFP-LC3 punctate dots per cell. Means ± s.d. for three independent experiments. Asterisk, P 0.001; two asterisks, P 0.01; ANOVA. (g) Immunostaining with anti-p62 (red) and anti-GFP (green) antibodies in starved A549 cells. Yellow indicates co-localization. N, nucleus. Scale bar, 10 μm. Each experiment was repeated three times.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(a, b) IB3-1 cells were transfected with either HA-tagged human beclin 1, empty vector, p62 siRNA or scrambled oligonucleotides followed by rosiglitazone (10 μM). (a) Cells were immunostained with anti-HDAC6 (red) and anti-PPAR-γ (green) antibodies. Yellow indicates co-localization. N, nucleus. Scale bar, 10 μm.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(a, b) IB3-1 cells were transfected with either HA-tagged human beclin 1, empty vector, p62 siRNA or scrambled oligonucleotides followed by rosiglitazone (10 μM).(b) FRET analysis of increase in PPAR-γ-Alexa 546 fluorescence after N-CoR Cy5 photobleaching.",
    "ncbi_link": "beclin 1: 8678
p62: 8878"
  },
  {
    "caption": "(c) IB3-1 cells were transfected with either HA-tagged human beclin 1 or the empty vector under nutrient starvation. Cells were immunostained with anti-LC-3 (red) and anti-CFTR (green). Yellow indicates co-localization. N, nucleus. Scale bar, 10 μm.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(e) IB3-1 cells were transfected with either 50 nM human beclin 1 siRNA or scrambled oligonucleotides in the presence or absence of 250 μM cystamine under nutrient starvation. Cells were immunostained with anti-p62 (red) and anti-CFTR (green) antibodies. Yellow indicates co-localization. N, cell nucleus. Scale bar, 10 μm.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(f, g) IB3-1 cells were transfected with 1 μg of pGFP-CFTRF508del or the empty vector, in the presence or absence of 250 μM cystamine. (f) Cells were immunostained with anti-GM-130 (red) and anti-GFP (green) antibodies. Yellow indicates co-localization (arrows). Scale bar, 10 μm. (g) FRET analysis of GFP fluorescence after HDAC6 Cy3 photobleaching. Each experiment was repeated three times. Quantitative measurement of co-localizations is shown in Supplementary Information, Fig. S9.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(a-d) IB3-1 cells transfected for 24 h at 37 °C with 1 μg of pGFP-CFTRF508del or empty vector in the presence or absence of 250 μM cystamine or with either 50 nM human p62 siRNA or scrambled oligonucleotides. (a) Left: CFTR revealed with anti-GFP primary antibody in IB3-1 cell lysate. Top arrow, complex-glycosylated form (apparent Mr of band C about 170K, revealed as 210K with GFP tag); bottom arrow, core-glycosylated form (apparent Mr of band B about 150K, revealed as 190K with GFP tag). Uncropped images of blots are shown in Supplementary Information, Fig. S10. Right: quantification of bands B (black) and C (white) normalized to β-actin levels. Values are means ± s.d. for three independent experiments.",
    "ncbi_link": "CFTR: 1080
p62: 8878"
  },
  {
    "caption": "(a-d) IB3-1 cells transfected for 24 h at 37 °C with 1 μg of pGFP-CFTRF508del or empty vector in the presence or absence of 250 μM cystamine or with either 50 nM humanp62 siRNA or scrambled oligonucleotides.(b) Cells immunostained with an anti-GFP antibody under non-permeabilizing conditions. Serial confocal sections were collected from top to bottom of cell. (c) Side view (X-Z) of a z-stack of confocal images taken in b. (c) Side view (X-Z) of a z-stack of confocal images taken in b.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(a-d) IB3-1 cells transfected for 24 h at 37 °C with 1 μg of pGFP-CFTRF508del or empty vector in the presence or absence of 250 μM cystamine or with either 50 nM humanp62 siRNA or scrambled oligonucleotides.(d) Surface biotinylation assays was performed with membrane-impermeable sulpho-NHS-LC-biotin. The cells were fractioned to obtain the plasma membrane fraction, and biotinylated proteins were precipitated with streptavidin beads. Immunoblot of GFP to reveal the C form. E-cadherin and β-actin were used as positive and negative controls, respectively.",
    "ncbi_link": "CFTR: 1080"
  },
  {
    "caption": "(e) IB3-1 cells transfected with either HA-tagged human beclin 1 or empty vector. Immunoblot of PIASy, TG2, phospho-p42/44 and PPAR-γ proteins.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(f) IB3-1 cells transfected with either 50 nM human p62 siRNA or scrambled oligonucleotides. Immunoblot of p62 and phospho-p42/44. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "(g) IB3-1 cells transfected with either 50 nM human beclin 1 siRNA or scrambled oligonucleotides in the presence or absence of cystamine. Immunoblot of phospho-p42/44.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "(h) IB3-1 cells transfected with either 50 nM humanbeclin 1 siRNA or 50 nM humanATG5 siRNA or scrambled oligonucleotides in the presence or absence of cystamine. TNF-α secretion. Each bar represents the mean ± s.d. for n = 3 experiments. Asterisk, P 0.01; ANOVA.",
    "ncbi_link": "ATG5: 9474
beclin 1: 8678"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (d) Immunoblot of beclin 1.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (e) Quantification of LC3 dots (per mm2 of lung tissue). Means ± s.d. Asterisk, P 0.01; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (f) Immunoblot of TG2. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (g) Confocal microscopy of SUMO-1 in lung tissues. Nuclei counterstained with DAPI (blue). Scale bar, 10 μm.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (h) Number of CD68+ macrophages counted in 15-20 different randomly taken sections. Means ± s.d. per mm2 of lung tissue from seven mice in each group. Asterisk, P 0.01; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(d-i) CftrF508del mice treated with cystamine or PBS in the presence or absence of 3-MA (e-i) (n = 7 per group). (i) MPO activity in lung homogenates (expressed as 10−3 × optical density (OD) s−1). Means ± s.d. for lung tissues from seven mice in each group. Asterisk, P 0.05; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "(j-m) CftrF508del mice (n = 3 per group) administered intranasally with a lentiviral vector encoding beclin 1 (LV-beclin 1) or GFP (LV-GFP). (j) TG2 Immunoblot in lung tissues. Uncropped images of blots are shown in Supplementary Information, Fig. S10.",
    "ncbi_link": "beclin 1: 56208
Cftr: 12638"
  },
  {
    "caption": "(j-m) CftrF508del mice (n = 3 per group) administered intranasally with a lentiviral vector encoding beclin 1 (LV-beclin 1) or GFP (LV-GFP). (k) Confocal microscopy of TG2 activity. Representative stainings from at least five airway epithelial areas per mouse from three mice per group. L, lumen. Scale bar, 10 μm.",
    "ncbi_link": "beclin 1: 56208
Cftr: 12638"
  },
  {
    "caption": "(j-m) CftrF508del mice (n = 3 per group) administered intranasally with a lentiviral vector encoding beclin 1 (LV-beclin 1) or GFP (LV-GFP). (l) Number of CD68+ macrophages counted in 15-20 different randomly taken sections. Means ± s.d. per mm2 of lung tissue. Asterisk, P 0.01; ANOVA.",
    "ncbi_link": "beclin 1: 56208
Cftr: 12638"
  },
  {
    "caption": "(j-m) CftrF508del mice (n = 3 per group) administered intranasally with a lentiviral vector encoding beclin 1 (LV-beclin 1) or GFP (LV-GFP). (m) MPO activity in lung homogenates (expressed as 10−3 × OD s−1). Means ± s.d. for lung tissues. Asterisk, P 0.05; ANOVA. Anti-β-Tubulin was used as loading control for immunoblot analysis. Densitometric analysis of blots is shown in Supplementary Information, Fig. S9.",
    "ncbi_link": "beclin 1: 56208
Cftr: 12638"
  },
  {
    "caption": "CftrF508del mice (a-d)(a) Confocal microscopy of LC3 (top) and p62 (bottom) in lung tissues from CftrF508del mice. Nuclei counterstained with DAPI (blue). Scale bar, 10 μm. Representative images of ten PBS-treated and ten NAC-treated mice. (b) Quantification of LC3 dots (per mm2 of tissue) in lung tissues from CftrF508del mice. Means ± s.d. Asterisk, P 0.001 versus PBS-treated mice; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "CftrF508del mice (a-d)(c) Number of macrophages per mm2 of lung tissue from CftrF508del mice (CD68-positive cells in 15-20 different randomly taken sections for each mouse lung for each condition); means ± s.d. for three separate experiments. Asterisk, P 0.05 versus PBS-treated mice; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "CftrF508del mice (a-d)(d) MPO activity in lung homogenates from CftrF508del mice (expressed as 10−3 × OD s−1). Means ± s.d. Asterisk, P 0.05 versus PBS-treated mice; ANOVA.",
    "ncbi_link": "Cftr: 12638"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (e) Confocal microscopy of LC3-positive dots in lung tissues from PBS-treated or NAC-treated mice-Tg LC3. Nuclei counterstained with DAPI (blue). Scale bar, 10 μm. (f) Number of LC3-positive dots in Scnn1b tissues from mice-Tg PBS. Means ± s.d. Asterisk, P 0.01 versus mice-treated mice; ANOVA.",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (g) FRET analysis of TG2-Alexa 546 fluorescence after SUMO-1 Cy5 photobleaching in lung tissues from PBS-treated WT mice and PBS-treated or NAC-treated Scnn1b-Tg mice.",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (h) Immunoblot of TG2 and phospho-p42/44 in lung tissues from PBS-treated WT mice and PBS-treated or NAC-treated Scnn1b-Tg mice. αβ-Tubulin was used as loading control.",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (i) Lung histology of PBS-treated and NAC-treated Scnn1b-Tg mice. Haematoxylin staining. Scale bar, 150 μm. Black arrows indicate decrease in lung infiltration in NAC-treated in comparison with PBS-treated mice (arrowheads).",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (j) Left: confocal microscopy of COX-2 staining (left) in PBS-treated and NAC-treated Scnn1b-Tg mice. Nuclei counterstained with DAPI (blue). Scale bar, 150 μm. Right; number of COX-2-positive cells per mm2 of lung tissue in NAC-treated and Scnn1b-treated mice-Tg PBS. Means ± s.d. Asterisk, P 0.05 versus mice-treated mice; ANOVA.1 versus PBS-treated mice; ANOVA.",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "Scnn1b-Tg mice (e-k) treated with NAC or PBS (n = 10 per group). (k) MPO activity in lung homogenates from PBS-treated and NAC-treated Scnn1b-Tg mice (expressed as 10−3 × OD s−1). Means ± s.d. Asterisk, P 0.05 versus PBS-treated mice; ANOVA. Densitometric analysis of the blot is shown in Supplementary Information, Fig. S9.",
    "ncbi_link": "Scnn1b: 20277"
  },
  {
    "caption": "(a) WT and dnm1Δ cells expressing Vph1-RFP and Idp1-GFP were grown in minimal synthetic dextrose medium and transferred to lactate medium at an initial density of OD600 0.08. The cells were then sampled daily and analysed by fluorescence microscopy (× 100 objective) during stationary phase mitophagy in lactate medium. Scale bar, 5 μm.",
    "ncbi_link": "dnm1: 850686
Idp1: 851493
Vph1: 854444"
  },
  {
    "caption": "(b) WT, dnm1Δ and dnm1Δ mgm1Δ mutants were grown in SL medium as described in Methods, and samples (10 OD600 units) were taken at each time point. Protein extracts were prepared and equal protein amounts (20 μg) were subjected to SDS-polyacrylamide gel electrophoresis and immunoblotting with anti-GFP antibody.",
    "ncbi_link": "dnm1: 850686
mgm1: 854386"
  },
  {
    "caption": "A comparison of the SILAC-derived abundance as a function of time, for several proteins that either show differential behaviour between WT and the mutants (Idh2, Idp1 and Aco2) and proteins that behave similarly between all the genetic backgrounds tested (Hsp78). Shown are mean protein ratios (two replicates for mutants, three replicates for WT), error bars indicating peptide-based relative s.d.",
    "ncbi_link": "Aco2: 853230
Hsp78: 851845
Idh2: 854303
Idp1: 851493"
  },
  {
    "caption": "WT (a), dnm1Δ (b) and atg1Δ cells (c) and atg32Δ cells (d) expressing chromosomally tagged GFP chimeras of Aco2, Idh2, Idp1 and Hsp78 were incubated in SL medium for 7 days, and 10 OD600 units were sampled at day 1 and day 7 and processed for immunoblotting with anti-GFP antibodies as described in the Methods section. Positive control used in c and d was from dnm1Δ cells expressing Idp1-GFP from a plasmid at 4-day incubation (Fig. 1b, lane 4). Release of free GFP in WT cells is reproducibly variable between these reporters, and varies between 0 (Idh2) and 60% (Aco2). (e) Densitometric quantification of the release of free GFP (as % of total signal) in four independent experiments, comparing the results between WT and dnm1Δ cells. Bars denote s.d. (n=4).",
    "ncbi_link": "Aco2: 853230
atg1: 852695
atg32: 854660
dnm1: 850686
Hsp78: 851845
Idh2: 854303
Idp1: 851493"
  },
  {
    "caption": "(a) Cells expressing chromosomally tagged GFP chimeras of Aco2, Idh2, Idp1 and Hsp78 as well as a plasmid-borne (pDJB12), mitochondrially targeted RFP (mtRFP) were incubated in SL-leucine medium for 3 days and imaged daily. Aco2 and Idp1 show clear mitophagic targeting (white arrows point at specific examples) by day 3, whereas Idh2 and Hsp78 show weak or no mitophagy. In addition, Idh2 and Hsp78 show different degrees of segregation relative to the mtRFP marker, whereas Idp1-GFP and Aco2-GFP show a near-complete co-localization with mtRFP. Scale bar, 5 μm. (b) Quantification of the frequency of mitophagy from a; the percentage of cells showing mitophagic profiles in the red (magenta bars; plasmid-borne mtRFP) or green (turquoise bars; integrated C-terminal GFP chimerae) was calculated for each GFP chimera. Idp-GFP, red N=76, green N=82; Aco2-GFP, red N=79, green N=82; Idh2-GFP, red N=72, green N=72; Hsp78-GFP, red N=70, green N=70.",
    "ncbi_link": "pDJB12: 
Aco2: 853230
Hsp78: 851845
Idh2: 854303
Idp1: 851493"
  },
  {
    "caption": "WT and dnm1Δ cells expressing integrated Hsp78-GFP and plasmid-borne mtRFP were grown on lactate medium for 3 days. Cells were imaged daily and the images were analysed using ImageJ as described in Methods. Graphs illustrate the distribution of pixels associated with specific values of RFP and GFP channel intensities, respectively. Diagonal concentrations of dots indicate spatial correlation between the signals. The coloured photographic panels at the bottom illustrate the increased intensity correlation of the two channels at the 3-day time point in the dnm1Δ mutant, relative to the WT cells. Scale bar, 5 μm.",
    "ncbi_link": "dnm1: 850686
Hsp78: 851845"
  },
  {
    "caption": "(A) Representative images of C9orf72 iPSC-cortical neurons treated with DMSO (vehicle control) or 1 µM of DB1246, DB1247 or DB1273, for 4 days. RNA foci are shown in red and nuclei (DAPI) in blue. Scale bar represents 10 µm.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(B) Quantification shows RNA foci are significantly reduced by all three compounds in iPSC-cortical neurons and by DB1246 and DB1273 in iPSC-motor neurons. Data are shown as the average percentage of neurons containing RNA foci relative to vehicle (DMSO). N=3 independent C9orf72 patient lines with 2-3 inductions per line and at least 70 neurons counted per induction. *p <0.05, **p <0.01, ***p <0.001, one sample two-tailed t-test versus normalised control. For cortical neurons, p=0.0124 (DB1246), p=0.0065 (DB1247), p=0.0096 (DB1273). For motor neurons, p=0.0004 (DB1246), p=0.0030 (DB1273).",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(A) Poly(GP) levels were measured by MSD immunoassay in C9orf72 patient iPSC-motor neurons treated for 7 days with 8-16 µM of the G4C2 repeat G-Q binding small molecules DB1247, DB1247 and DB1273. Treatment with DB1246 or DB1273 leads to a significant reduction in poly(GP) levels relative to vehicle-treated controls. Data are shown as the mean and SEM of 3 independent C9orf72 iPSC lines, with 1-6 differentiations per line. *p<0.05, **p<0.01, *** p<0.001, one sample two-tailed t-test versus normalised control. p=0.0068 (DB1246, 12 µm), p=0.0417 (DB1246, 16 µm), p=0.0196 (DB1247, 8 µm), p=0.0002 (DB1273, 8 µm), p=0.0194 (DB1273, 12 µm), p=0.0062 (DB1273, 16 µm)",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(B) C9orf72 patient iPSC-motor neurons were treated for 7 days with 16 µM of each small molecule and the expression levels of MCM2 and the three C9orf72 transcript variants (V1-V3) measured by quantitative RT-PCR. Data are shown as the mean and s.d. of 3 independent iPSC-motor neuron lines (one induction per line) relative to vehicle (DMSO) treated controls. No significant changes in gene expression were observed, one way ANOVA, Dunnett's post hoc test, p>0.05.",
    "ncbi_link": "C9orf72: 203228
MCM2: 4171"
  },
  {
    "caption": "(C) XTT cell death assay for C9orf72 iPSC-motor neurons treated for 7 days with 0 - 40 µM of DB1246, DB1247, DB1273 or cisplatin as a positive control. Data are shown as the mean and SEM of two independent iPSC-motor neuron lines. Toxicity is only observed at the highest dose of 40 µM and not at the penultimate dose of 20 µM.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": " B-C Competitor donor derived Gr, B, CD4 T, and CD8 T cells in the peripheral blood. In the control group, competitor donor cells are WT HSCs. In the deficient group, competitor donor cells are uMT-/- or NSG HSCs Data information: Data are shown as percentages of the total number of white blood cells (WBCs). Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05, **p<0.01, ***p<0.001 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090
NSG: 19090///16186"
  },
  {
    "caption": " D-E WT donor derived Gr, B, CD4 T, and CD8 T cells in the peripheral blood Data information: Data are shown as percentages of the total number of white blood cells (WBCs). Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05, **p<0.01, ***p<0.001 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090"
  },
  {
    "caption": " F-G Total production of Gr, B, CD4 T, and CD8 T cells in the peripheral blood (derived from WT HSCs, competitor HSCs, helper whole bone marrow cells, and residual host cells) shown as percentages of the total number of white blood cells (WBCs). Data information: Data are shown as percentages of the total number of white blood cells (WBCs). Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05, **p<0.01, ***p<0.001 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090"
  },
  {
    "caption": " A-B Total numbers of barcoded WT clones that give rise to granulocytes (Gr), B cells, CD4 T cells, and CD8 T cells Data information: Data were collected at month 7 post-transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090"
  },
  {
    "caption": " C-J Number of HSC clones that produce different amounts of Gr, B, CD4 T, and CD8 T cells. We combined the sequencing data with the flow cytometry data to calculate clonal abundance for each clone as follows: Clonal abundance =100%*(Each cell population (Gr, B, CD4T or CD8T cells) % WBCs) * (Donor % Each cell population) * (GFP % Donor cells) * (number of reads for each barcode) / (total reads of all barcodes Data information: Data were collected at month 7 post-transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090"
  },
  {
    "caption": " K-L Production of Gr, B, CD4 T, and CD8 T cells by expanding WT clones that produce more than 0.1% of WBCs in each lineage. Data information: Data were collected at month 7 post-transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 19090///16186"
  },
  {
    "caption": " A-B Total amount of progenitors as a percentage of ckit and Il7rα enriched bone marrow (BM) cells. Shown are hematopoietic stem cells (HSCs), Flk2- and Flk2+ multipotent progenitors (MPP), common lymphoid progenitors (CLP), common myeloid progenitors (CMP), megakaryocyte-erythroid progenitors (MEP), and granulocyte-monocyte progenitors (GMP) Data information: Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05 and **p< 0.01 (two-tailed and two-sample equal variance Student"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090"
  },
  {
    "caption": " C-D WT donor derived progenitors as a percentage of ckit and Il7rα enriched BM cells. Data information: Data were collected at month 7 post transplantation for the uMT-/- group and month 8 post-transplantation for the NSG group, and presented as mean ± SEM. n=7 mice for the uMT-/- group and n=6 for the NSG group. *p<0.05 and **p< 0.01 (two-tailed and two-sample equal variance Student\"s t-test) ",
    "ncbi_link": "uMT: 16019
NSG: 16186///19090
NSG: 19090///16186"
  },
  {
    "caption": "(B) Overview of electroporated neocortices showing Cas9 expression as revealed by PaprikaRFP fluorescence (magenta) and the effects of Cas9 expression, together with control gRNA (top) or gGFP (bottom), on GFP expression (green, fluorescence). Dotted lines indicate the electroporated area of the VZ. Single optical sections; scale bars, 200 μm.",
    "ncbi_link": "gGFP: 
gRNA: 
Cas9: 901176"
  },
  {
    "caption": "(C) Higher magnification of the VZ and SVZ of the electroporated area shown in (B), with DAPI staining (blue) depicted in addition to PaprikaRFP (Cas9) and GFP fluorescence. Boxes indicate areas shown at higher magnification in the insets (35 x 35 μm). Dotted lines indicate nuclei of progeny of electroporated aRGCs; note the presence of GFP fluorescence in the control (top) and its absence upon Cas9/gGFP electroporation (bottom). Images are single optical sections. Scale bars, 20 μm.",
    "ncbi_link": "gGFP: 
Cas9: 901176"
  },
  {
    "caption": "(D) Quantification of the proportion of Cas9-positive cells in the VZ plus SVZ that are GFP-positive 48 h after control (Con, white) or gGFP (black) Cas9 plasmid electroporation. Data are the mean of 4 independent experiments (7 embryos per condition in total, from 4 litters).",
    "ncbi_link": "gGFP: 
Cas9: 901176"
  },
  {
    "caption": "(F) Overview of electroporated areas of neocortices as revealed by mCherry fluorescence (magenta) showing the effects of Cas9 protein together with either control gRNA (top) or gGFP (bottom) on GFP expression (green, fluorescence). Dotted lines indicate the electroporated area of the VZ. Single optical sections; scale bars, 200 μm.",
    "ncbi_link": "gGFP: 
gRNA: "
  },
  {
    "caption": "(G) Higher magnification of the VZ and SVZ of the electroporated area shown in (F), with DAPI staining (blue) depicted in addition to mCherry and GFP fluorescence. Boxes indicate areas shown at higher magnification in the insets (35 x 35 μm). Dotted lines indicate nuclei of progeny of electroporated aRGCs; note the presence of GFP fluorescence in the control (top) and its absence upon Cas9/gGFP electroporation (bottom). Images are single optical sections. Scale bars, 20 μm.",
    "ncbi_link": "gGFP: 
Cas9: 901176"
  },
  {
    "caption": "H) Quantification of the proportion of mCherry-positive cells in the VZ plus SVZ that are GFP-positive 48 h after control (Con, white) or gGFP (black) Cas9 protein electroporation. Data are the mean of 4 independent experiments (5 embryos per condition in total, from 4 litters).",
    "ncbi_link": "gGFP: 
Cas9: 901176"
  },
  {
    "caption": "(I) VZ and SVZ of the electroporated areas showing Cas9 expression as revealed by PaprikaRFP fluorescence (magenta) and the effects of Cas9 expression, together with control gRNA (top) or gGFP (bottom), on GFP expression (green, fluorescence); blue, DAPI staining. Boxes indicate areas shown at higher magnification in the insets (35 x 35 μm). Dotted lines indicate nuclei of progeny of electroporated aRGCs; note the presence of GFP fluorescence in the control (top) and its absence upon Cas9/gGFP electroporation (bottom). Images are single optical sections. Scale bars, 20 μm.",
    "ncbi_link": "gGFP: 
gRNA: 
Cas9: 901176"
  },
  {
    "caption": "(J) VZ and SVZ of the electroporated areas showing targeted cells as revealed by mCherry fluorescence (magenta) and the effects of Cas9 protein together with either control gRNA (top) or gGFP (bottom) on GFP expression (green); blue, DAPI staining. Boxes indicate areas shown at higher magnification in the insets (35 x 35 μm). Dotted lines indicate nuclei of progeny of electroporated aRGCs; note the presence of GFP fluorescence in the control (top) and its absence upon Cas9/gGFP electroporation (bottom). Images are single optical sections. Scale bars, 20 μm.",
    "ncbi_link": "gGFP: 
gRNA: 
Cas9: 901176"
  },
  {
    "caption": "K) Quantification of the proportion of Cas9-positive cells (left) and mCherry-positive cells (right) in the VZ plus SVZ that are GFP-positive 24 h after control (Con, white) or gGFP (black) Cas9 plasmid (left) or protein (right) electroporation. Data are the mean of 3 independent experiments each (3 embryos per condition in total, from 3 litters).(D, H, K) Controls were set to 100% and the gGFP conditions expressed relative to control (D, 11%; H, 24%; K left, 40% K right, 28%). Error bars indicate SD; *, P<0.05; **, P<0.01; ***, P<0.001.",
    "ncbi_link": "gGFP: 
Cas9: 901176"
  },
  {
    "caption": "(B) Daughter cells of single aRGCs microinjected with either Cas9/control gRNA (top) or Cas9/gGFP (bottom) revealed by Dx-A555immunofluorescence (magenta); Cells 1, aRGC daughter; Cells 2, BP daughter. Dashed lines indicate ventricular surface. Images are maximum intensity projections of 20 (Control) and 24 (gGFP) optical sections. Scale bars, 20 µm.",
    "ncbi_link": "gGFP: 
gRNA: "
  },
  {
    "caption": "(C) Single optical sections of Cells 1 and Cells 2 depicted in (B), showing the effects of Cas9 and control gRNA (top) or gGFP (bottom) on GFP expression (as revealed by immunofluorescence, green). Cells 1 and Cells 2 are indicated by dotted lines; note the presence of GFP immunofluorescence in the daughter cells in control and its absence upon Cas9/gGFP microinjection. Scale bars, 5 µm.",
    "ncbi_link": "gGFP: 
gRNA: "
  },
  {
    "caption": "(D) Quantification of the proportion of daughter cells (Dx-A555+) of microinjected cells that show GFP expression 24 h after control (Con, white) or gGFP (black) microinjection. Control is set to 100% and the gGFP condition expressed relative to control (39%). Data are the mean of two independent experiments (3 embryos and 1 litter per experiment, total number of daughter cells scored: control 142, gGFP 88); bars indicate the variation of the two individual values from the mean (P<0.05).",
    "ncbi_link": "gGFP: "
  },
  {
    "caption": "(A-D) Neocortex of mouseE13.5embryos was in utero electroporated with a plasmid encoding, under constitutive promoters, Cas9_T2A_PaprikaRFP and gRNA targeting either LacZ (Control, Con) or Tbr2 (Tbr2), followed by analysis at E15.5.(A) Electroporated area showing the effects of Cas9 expression (revealed by PaprikaRFPDAPI, magenta) together with either control gRNA (top) or gTbr2 (bottom) on aRGCs expression (green, immunofluorescence); blue, Cas9staining. Boxes indicate areas shown at higher magnification in the insets (45 x 45 μm). Dotted lines indicate nuclei of progeny of electroporated Cas9; note the presence of Tbr2 immunoreactivity in the control (top) and its absence upon Cas9/gTbr2 plasmid electroporation (bottom). Scale bars, 20 μm.",
    "ncbi_link": "gRNA: 
LacZ: 
gTbr2: 13813
Tbr2: 13813"
  },
  {
    "caption": "(B) Quantification of the proportion of Cas9+ cells that are Tbr2+ 48 h after control (Con, white) or gTbr2 (black) plasmid electroporation. Data are the mean of 4 independent experiments (6 embryos per condition, from 4 litters).",
    "ncbi_link": "gTbr2: 13813"
  },
  {
    "caption": "(C) Electroporated area showing the effects of Cas9 expression (revealed by PaprikaRFP fluorescence, magenta) together with either control gRNA (top) or gTbr2 (bottom) on the abundance of mitotic progenitors as revealed by phosphohistone H3 (PH3) immunofluorescence (green). Apical and basal mitoses are indicated by arrows and arrowheads, respectively; note the reduction in mitotic Cas9+ BPs upon Cas9/gTbr2 plasmid electroporation. Scale bars, 20 μm.",
    "ncbi_link": "gRNA: 
gTbr2: 13813"
  },
  {
    "caption": "(D) Quantification of apical and basal Cas9+ mitoses (as revealed by PH3 immunofluorescence) in a unit area 48 h after Cas9/gTbr2 plasmid electroporation. Data are expressed as percentage of the data obtained upon control plasmid electroporation and are the mean of 3 independent experiments (3 embryos per condition in total, from 3 litters); note the reduction in basal (black, 68%) but not apical (white) mitoses.",
    "ncbi_link": "gTbr2: 13813"
  },
  {
    "caption": "(E-H) Single aRGCs in neocortex in organotypic slices of telencephalon of E14.5 mouse embryos were microinjected with recombinant Cas9 protein together with gRNA targeting either LacZ (Control, Con) or Tbr2 (gTbr2) and with Dextran 10,000-Alexa 555 (Dx-A555), followed by analysis after 48 h of culture.(E) Progeny of single microinjected aRGCs (revealed by Dx-A555immunofluorescence, magenta, dotted lines) showing the effects of Cas9 together with either control gRNA (top) or gTbr2 (bottom) on Tbr2 expression (green, immunofluorescence); blue, DAPI staining. Note the presence of Tbr2 immunoreactivity in the control (top) and its absence upon Cas9/gTbr2 (bottom) protein microinjection. Images are single optical sections. Scale bars, 5 µm.",
    "ncbi_link": "gRNA: 
LacZ: 
gTbr2: 13813
Tbr2: 13813"
  },
  {
    "caption": "(F) Quantification of the proportion of the progeny (Dx-A555+) of microinjected aRGCs that show Tbr2 expression 48 h after control (Con, white) or gTbr2 (black) microinjection. Data are the mean of 3 independent experiments (3 embryos per condition; total number of cells scored: control 45, gTbr2 41).",
    "ncbi_link": "gTbr2: 13813"
  },
  {
    "caption": "(G) Distribution across the cortical wall of the progeny (revealed by Dx-A555immunofluorescence, magenta; arrows, aRGC; arrowheads, BPs; open arrow, neuron) of single control (left) or gTbr2 (right) microinjected aRGCs. Dashed lines indicate ventricular surface (bottom) and basal lamina (top). Images are maximum intensity projections of 67 (Control) and 94 (gTbr2) single optical sections. Scale bars, 20 µm.",
    "ncbi_link": "gTbr2: 13813"
  },
  {
    "caption": "(H) Quantification of the distribution of the progeny (Dx-A555+) of microinjected aRGCs in the VZ, SVZ and intermediate zone/cortical plate (CP+IZ) 48 h after control (Con, white) or gTbr2 (black) microinjection (total number of cells scored: control 37, gTbr2 51, pooled from at least 3 independent experiments). Note that upon gTbr2 microinjection the distribution of cells across the various cortical zones is significantly different (VZ: control 77%, gTbr2 39: SVZ: control 20%, gTbr2 37%; IZ/CP: control 3%, gTbr2 24%, *, P<0.05).(B, F) Controls were set to 100% and the gTbr2 conditions expressed relative to control (B, 48%; F, 50%).(B, D, F) Error bars indicate SD (B, D, F); *, P<0.05; **, P<0.01.",
    "ncbi_link": "gTbr2: 13813"
  },
  {
    "caption": "Figure 4. Sequencing analysis of the CRISPR/Cas9-induced disruption of the Tbr2 locus.(A-C) Next-generation DNA sequencing analysis of amplicons containing the Tbr2 locus and 4 off-target loci generated from PaprikaRFP-expressing cells isolated at E15.5 from neocortex of mouse embryos in utero electroporated at E13.5 with plasmids encoding Cas9_T2A_PaprikaRFP and either gTbr2 (black) or control gRNA (Con, white) as in Fig 3 A-D.(A) Quantification of the frequency of mismatches to the mouse genome sequence spanning 30 bp upstream and downstream of the Tbr2 target site and the off-target sites (OT1-4). Data are expressed as percentage of the total number of reads and are the mean of two independent experiments (8 and 5 embryos per condition, respectively).(B, C) Analysis of one of the experiments of (A) for deletions (B) and insertions (C) in the region spanning 80 bp upstream and downstream of the Tbr2 target site upon Cas9/gTbr2 plasmid electroporation.",
    "ncbi_link": "gRNA: 
OT1: 
gTbr2: 13813
Tbr2: 13813
Cas9: 901176"
  },
  {
    "caption": "A. HEK293 Tet-off experiments showing the degradation of REL-OPT and REL-WT transcripts (left) as well as IL6-OPT, IL6-WT and IL6-DE transcripts (right), post-doxycycline addition. Data information: data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***). The half-lives of the respective transcripts are indicated in brackets.",
    "ncbi_link": "IL6: 3569
REL: 5966"
  },
  {
    "caption": "B. Representative immunoblot of FLAG-tagged REL-OPT and REL-WT in HEK293T cells transfected with either empty plasmids, plasmids bearing REL-OPT or REL-WT. The immunoblot is representative of 3 independent experiments. ACTB is shown as the loading controls.",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "C. ELISA of secreted IL6 concentrations of IL6-OPT, IL6-WT and IL6-DE from HEK293T cells transfected with plasmids bearing IL6-OPT, IL6-WT and IL6-DE. Data information: In (C), the data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A one-way ANOVA with Tukey's multiple comparisons was performed between samples where, p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "D. Fold changes of REL-OPT and REL-WT transcript levels (top) relative to their abundances from fraction 1 as detected by qPCR across polysome fractions (below). Data represents the mean ± SD for 3 biological replicates. Data information data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***). The half-lives of the respective transcripts are indicated in brackets.",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of REL-OPT and REL-WT transcripts under vehicle (DMSO)- and cycloheximide (CHX)-treatment, post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of IL6-OPT, IL6-WT and IL6-DE transcripts (B), under vehicle (DMSO)- and cycloheximide (CHX)-treatment, post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of REL-OPT and REL-WT transcripts (C) under vehicle (PBS)- and anisomycin (ANI)-treatment, post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of IL6-OPT, IL6-WT and IL6-DE transcripts (D), under vehicle (PBS)- and anisomycin (ANI)-treatment, post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of REL-OPT, REL-OPT (+1 Frameshift) and REL-WT transcripts (E) post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "HEK293 Tet-off experiments showing the degradation of IL6-OPT, IL6-WT, IL6-DE and IL6-OPT (+1 Frameshift) transcripts (F) post-doxycycline addition. data is representative of 3 independent experiments each with 3 replicates. The data represents the mean ± SD for 3 replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**) and p<0.001 (***).",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "Volcano plots showing the enrichment of RBPs which bind to REL-WT relative to REL-OPT transcripts (A) Data information: vertical dotted lines indicate a 1.5-fold enrichment while horizontal dashed lines indicate the p-value cut-off of 0.05. Points shaded in blue indicate RBPs which have a differential fold change of more than 1.5 and p<0.05.",
    "ncbi_link": "REL: 5966"
  },
  {
    "caption": "Volcano plots showing the enrichment of RBPs which bind to , IL6-DE relative to IL6-WT transcripts (B) Data information: vertical dotted lines indicate a 1.5-fold enrichment while horizontal dashed lines indicate the p-value cut-off of 0.05. Points shaded in blue indicate RBPs which have a differential fold change of more than 1.5 and p<0.05.",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "Volcano plots showing the enrichment of RBPs which bind to IL6-WT relative to IL6-OPT transcripts (C). Data information: , vertical dotted lines indicate a 1.5-fold enrichment while horizontal dashed lines indicate the p-value cut-off of 0.05. Points shaded in blue indicate RBPs which have a differential fold change of more than 1.5 and p<0.05.",
    "ncbi_link": "IL6: 3569"
  },
  {
    "caption": "A. Cumulative distribution plots showing the difference in distribution of transcript optimality between upregulated and downregulated transcripts in K562 cells subject to ILF2 CRISPR interference targeting ILF2. Transcript quantities are indicated in the figure legend. Data information: Wilcoxon signed rank tests were performed on the upregulated and downregulated groups against the control group. P-values are denoted (right).",
    "ncbi_link": "ILF2: 3608"
  },
  {
    "caption": "B, C. HEK293 Tet-off experiments showing the degradation of REL-OPT (B) and REL-WT (C) transcripts with ILF2 and ILF3 siRNA and Control (CTR) siRNA treatment, post-doxycycline addition. Data information: data is representative of 3 independent experiments in which the data represents the mean ± SD for 3 biological replicates. A two-way ANOVA with Holm-Sidak multiple comparisons was performed. P-values are denoted as follows: p < 0.05 (*), p<0.01 (**).",
    "ncbi_link": "ILF2: 3608
ILF3: 3609
REL: 5966"
  },
  {
    "caption": "D. Representative immunoblot of FLAG-tagged REL-OPT and REL-WT expressed in HEK293T cells under ILF2 and ILF3 siRNA treatment. The immunoblot is representative of 3 independent experiments. ACTB is shown as loading controls.",
    "ncbi_link": "FLAG: 
ILF2: 3608
ILF3: 3609
REL: 5966"
  },
  {
    "caption": "E. Representative immunoblot of FLAG-tagged REL-OPT and REL-WT in HEK293T cells co-expressed with two different isoforms of ILF2. The immunoblot is representative of 3 independent experiments. ACTB is shown as loading controls.",
    "ncbi_link": "FLAG: 
ILF2: 3608
REL: 5966"
  },
  {
    "caption": "C) Changes of the 3209 proteins detected on the cell surface of SEZ6KO neurons compared to WT. The average log2 fold change of SEZ6KO neurons over WT (log2 SEZ6KO/WT) is plotted against the negative log10 of each protein's p-value according to a one-sample t test. Blue labeled dots are considered as hits (including GluK2 and GluK3) and are proteins with a p-value less than 0.05 (neg. log10(0.05)=1.3; horizontal dotted line) and a fold-change to less than -0.5 or more than 0.5 (vertical dotted lines). GluK2 and GluK3 are labeled in pink, GluA1 and GluA2 are indicated with green lines and dots and GluN1 and GluN2B are marked with red lines and dots.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "A) SEZ6KO and WT neurons were biotinylated with Sulfo-NHS-Biotin and surface proteins were enriched by streptavidin bead pull-down. The GluK2/3 antibody cannot discriminate the subunits 2 and 3 (Lerma & Marques, 2013), therefore the band is commonly indicated with the labeling GluK2/3. GluK2/3, GluA2 and GluN2B surface levels were quantified, normalized to SEZ6L2 surface levels (negative control) in the same sample (GluK2/3 / SEZ6L2) and divided by the WT levels, with the ratio for WT being set to 1.0 (plot shows mean ± S.E.M., at least 10 replicates in 4 independent biological experiments, Mann-Whitney ****p-value<0.005).",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "B) mRNA levels of GluA1, GluA2, GluK2, GluK3 and GluN2B were quantified in SEZ6KO neurons, normalized to GAPDH and β-actin mRNA in the same sample and compared to the mRNA levels in WT neurons. No difference in GluK2/3 mRNA was detected in SEZ6KO neurons compared to WT (plot shows mean ± SD, 6 replicates in 2 independent biological experiments, multiple t-test was used).",
    "ncbi_link": "GAPDH: 
β-actin: 
GluA1: 14799
GluA2: 14800
GluK2: 14806
GluK3: 14807
GluN2B: 14812
SEZ6: 20370"
  },
  {
    "caption": "C) Editing of GluK2 mRNA was tested in SEZ6KO and WT neurons. The editing value was calculated as (intensity of 376 [edited] / intensity of [376 (edited) + 269 (unedited)]) × 100 and normalized to the band at 76 bp. No difference was detected in SEZ6KO neurons compared to WT (plot shows mean ± S.E.M., 6 replicates in 2 independent biological experiments, Mann-Whitney test was used).",
    "ncbi_link": "GluK2: 14806
SEZ6: 20370"
  },
  {
    "caption": "(A) Left: Current trace resulting from whole-cell voltage-clamp recordings at a holding potential of -70 mV in a CA1 pyramidal neuron in a WT mouse hippocampal slice (P15). The current was recorded in the presence of 10 µM bicuculline, 20 µM GYKI53655 and 30 µM APV in the ACSF. Perfusion of the recording chamber with 10 µM kainate and 100 µM 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) are indicated with green and blue bars, respectively. Right: Analogous experiment in a SEZ6KO mouse (P15). (B) Summary of the experiments in A. Bar graph illustrates mean charge with standard error of the mean carried by the inward currents (measured as area under the curve, AUC) for the two genotypes at P15 (WT 46.6 ± 0.5 nC (n=10 cells), SEZ6KO 30.8 ± 0.5 nC (n=9 cells), *p=0.0375 Mann-Whitney-U-test). ",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "A) In WT neurons, GluK2/3 was seen as two closely comigrating bands, whereas the upper one of lower intensity was missing or running even more closely to the lower band of main intensity in SEZ6KO neurons (schematic representation on the right). When the total lysates of SEZ6KO and WT neurons were digested with endoglycosidase H (EndoH) - which removes immature, but not mature sugars - the two closely comigrating bands were converted to three bands of a lower apparent molecular weight, consistent with full deglycosylation of the lowest band and a partial deglycosylation of the upper two bands (marked in light blue, red and green in the right panel). In SEZ6KO neurons the uppermost (light blue) band was missing and a new band of lower apparent molecular weight was seen that was overlapping with the red labeled band and was indicated with the purple asterisk in the SEZ6KO. No difference in the glycosylation of GluA2 was detectable, pointing to a specific effect of SEZ6 on GluK2/3.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "B) The running pattern of GluK2/3 in SEZ6KO and WT brains was compared upon EndoH digestion. Similar to primary neurons, GluK2/3 displayed an immature glycosylation pattern in SEZ6KO brains.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "C) Total GluK2/3 levels were quantified and showed a significant but moderate reduction in SEZ6KO compared to WT neuronal lysates (plot shows mean ± S.E.M., 9 replicates in 3 independent biological experiments, Mann-Whitney **p-value=0.0012). D) No significant change in GluK2/3 total levels was detectable in SEZ6KO and WT adult brains (plot shows mean ± S.E.M., 6 replicates, Mann-Whitney test was used). ",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "E) Synaptosomes from knock-out (KO) brains of single SEZ6 family members (SEZ6, SEZ6L, SEZ6L2), triple knock-out (TKO) and respective controls (WT and TWT - triple WT) were digested with EndoH. GluK2/3 displayed the immature glycosylation in SEZ6KO and TKO brains, but not in SEZ6L and SEZ6L2 brains, demonstrating non-redundant functions for the SEZ6 family members. (n=4)",
    "ncbi_link": "SEZ6: 20370
SEZ6L: 56747
SEZ6L2: 233878"
  },
  {
    "caption": "F) Brain homogenates from SEZ6KO and WT mice at different ages were digested with EndoH. GluK2/3 displayed the immature glycosylation at all developmental stages of SEZ6KO mice, suggesting that no compensation effect is occurring with aging.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "A) The glycome fingerprint of GluK2/3 was analyzed by lectin chip microarray (LecChip). Lectin PHAL and PHAE (indicated with asterisks) detected reduced amounts of the oligosaccharide Galβ1-4GlcNAcβ1 on GluK2/3 in SEZ6KO neurons (plot shows mean ± S.E.M., 3 WT replicates and 4 SEZ6KO replicates were used, discoveries were determined using the FDR method of Benjamini and Hochberg, with Q = 2%).",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "B) Immunoblot analysis revealed reduction of HNK-1 epitope on GluK2/3 in SEZ6KO brains. Left panels: Comparable amounts of GluK2/3 were immunoprecipitated (IP) in WT and SEZ6KO brains using excess of brain homogenates compared to beads. Anti-HNK-1 antibody was used for detection. HNK-1 band on GluK2/3 was detected only in WT brains but not in SEZ6KO brains (n=6). As a control, HNK-1 modification of NCAM-1 was unaltered, as revealed after IP of NCAM-1 from WT and SEZ6KO brains (n = 3), followed by detection with anti-HNK-1 antibody. Different isoforms of NCAM-1 are annotated with arrowheads (NCAM 180, NCAM 140 and NCAM 120). Mid panel: To prove the specificity of the HNK-1 antibody, GluK2/3 was immunoprecipitated and digested with Peptide-N-Glycosidase F (PNGase F), which removes N-linked oligosaccharides. Upon PNGase F digestion, HNK-1 was not detectable in WT brains and the molecular weight of GluK2/3 was reduced (n=2). Right panels: In total brain homogenates (input), no difference of general HNK-1 epitope or NCAM-1 levels was detected.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "B,C) The constitutively ER-retained SEZ6 mutant SEZ6∆cytoER-HA (B) and full length wild-type SEZ6FL-HA (C) were co-transfected with SBP-GFP-GluK2. Biotin was added to elicit release of SBP-GFP-GluK2 from the ER (0 min) and cells were fixed at different time points (0, 20 and 40 min). HA-tagged SEZ6FL and SEZ6∆cytoER transgenes were labeled with anti-HA (mouse) and anti-mouse-Alexa594 antibodies. Size bars represent 5 µm.",
    "ncbi_link": "GFP: 
HA: 
SBP: 
GluK2: 14806
SEZ6: 20370"
  },
  {
    "caption": "D) Scatter dot plot represents number of vesicles per cell in SBP-GFP-GluK2 RUSH experiment with SEZ6∆cytoER-HA (control) or SEZ6FL-HA co-transfection. Vesicle counts from 15 to 28 cells per timepoint from 2 independent experiments with mean number of vesicles and error bars (SD) are shown. Mann-Whitney test was used to compare HA-tagged SEZ6FL and SEZ6∆cytoER at each time point. At 20 min ***p-value=0.0007, at 40 min ****p-value<0.0001.",
    "ncbi_link": "GFP: 
HA: 
SBP: 
GluK2: 14806
SEZ6: 20370"
  },
  {
    "caption": "A) Representative pictures of WT hippocampal neurons transfected with the SBP-mCherry-GluK2 RUSH construct, followed by treating neurons with biotin and anti-SBP antibodies (mouse, green) for 20 min or 40 min to live-label the GluK2 transported to the neuronal cell surface. As a control (no biotin), neurons were incubated only with SBP antibody for 40 min. The surface/total ratio of SBP-mCherry-GluK2 constructs was estimated by calculating the ratio of SBP (green)/ mCherry (red) fluorescence signals in the same area chosen for quantification. B) Quantification results for A, indicating that incubation with biotin increases the surface/total ratio of SBP-mCherry-GluK2 over time. No Biotin n=16, 20 min n=13, 40 min n=15, all biological replicates. Graph shows mean±SEM, 1-way ANOVA p<0.0001 and Dunnett's post hoc test, No Biotin vs 20 min *p=0.0030; No Biotin vs 40 min ***p<0.0001.",
    "ncbi_link": "mCherry: 
SBP: 
GluK2: 54257"
  },
  {
    "caption": "C-D) SEZ6 flox/flox neurons were lentivirally infected with inactivated Cre (Y324F, Ctrl) or Cre recombinase (SEZ6KO), followed by transfection with the SBP-mCherry-GluK2 construct and treated with biotin and anti-SBP antibodies (mouse, green) for 20 min. Expression of inactivated Cre or Cre recombinase were confirmed by immunostaining with an anti-Cre antibody (rabbit, blue). SEZ6KO neurons showed a significantly reduced surface/total ratio of SBP-mCherry-GluK2 (ctl n=25, SEZ6KO n=23 biological replicates. Graph shows mean ± SEM, unpaired t-test, **p=0.0068).",
    "ncbi_link": "mCherry: 
SBP: 
Cre: 2777477
GluK2: 54257
SEZ6: 20370"
  },
  {
    "caption": "B, SEZ6 constitutive KO neurons were transduced with SEZ6 constructs. SEZ6FL and SEZ6Δcyto were detectable as two bands corresponding to mature (higher) and immature (lower) forms of SEZ6. No difference in the apparent molecular weight was detected because the high percentage of the gel used (12%) and the small C-terminal deletion (39 amino acids). SEZ6ecto was present as the immature band in the neuronal lysates SEZ6CTF (with HA and Flag-tags) was detected at the expected low molecular weight. Additionally, the C-terminal fragment generated from SEZ6FL by BACE1 cleavage was detected. Due to its lack of an HA-tag, it had a lower molecular weight than SEZ6CTF. The C-terminal fragment generated from SEZ6Δcyto upon BACE1 cleavage was not visible because of its low molecular weight. GluK2/3 glycosylation was rescued when SEZ6FL, SEZ6Δcyto and SEZ6ecto were expressed in the neurons, but SEZ6CTF was not able to rescue the phenotype. Color coding for asterisks is the same as in figure 4A. Representative blot of 3 independent experiments.",
    "ncbi_link": "SEZ6: 20370"
  },
  {
    "caption": "D) Sez6 constitutive KO neurons were transduced with SEZ6ΔcytoER and SEZ6Δcyto. SEZ6ΔcytoER presented only the band corresponding to the immature form of SEZ6, as expected for a protein retained in the ER. SEZ6Δcyto, but not SEZ6ΔcytoER, was able to rescue GluK2/3 glycosylation, showing that SEZ6 localized to the ER is not sufficient to rescue the GluK2/3 glycosylation (n=5). Color coding for asterisks is the same as in figure 4A.",
    "ncbi_link": "Sez6: 20370
SEZ6: 20370"
  },
  {
    "caption": "E) HEK293T cells were co-transfected with a GluK2a plasmid and the SEZ6 constructs. Expression of SEZ6 constructs was analyzed in the total lysates ("Input") and revealed a similar expression of the different proteins. GluK2a was immunoprecipitated with GluK2/3 antibody and the SEZ6 mutants were detected with the HA.11 antibody ("IP"). SEZ6FL, SEZ6Δcyto and SEZ6ecto, but not SEZ6CTF were co-immunoprecipitated with GluK2a, suggesting that SEZ6 extracellular domain is necessary for GluK2a binding. Representative blot of 2 independent experiments. * indicates the light chain of the antibody used for immunoprecipitation.",
    "ncbi_link": "GluK2a: 14806
SEZ6: 20370"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. Representative confocal microscopy images of CMAC-stained conjugates formed between B lymphocytes (isolated from DICER-KO mouse splenocytes and pre-activated with a mixture of LPS plus IL-4) and CD4+ T cells (from OVA-specific OT-II transgenic mice); conjugates were formed either in the presence or in the absence of OVA. A representative experiment of at least 3 independent experiments is shown.",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. showing the percentage of B cells forming conjugates",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. the accumulation at the IS of the TCR Conjugates were assessed using the Image J plug-in for IS analysis",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. the accumulation of the actin at the IS Conjugates were assessed using the Image J plug-in for IS analysis",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. the distance from the CD4+ T cell MTOC to the contact site with the B cell MTOC-B-cell distance was measured with Imaris analysis software.",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. Flow cytometry analysis of B lymphocytes co-cultured with OT-II isolated T cells in the presence or absence of OVA, showing IgG1 expression after 24h of co-culture,",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. Flow cytometry analysis of B lymphocytes co-cultured with OT-II isolated T cells in the presence or absence of OVA B cell proliferation after 24h, 48h and 72h co-culture (Ki67 expression in live B cells and cell violet tracer dilution, respectively)",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. B cell proliferation after 24h, 48h and 72h co-culture (Ki67 expression in live B cells and cell violet tracer dilution, respectively),",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. Flow cytometry analysis of B lymphocytes co-cultured with OT-II isolated T cells in the presence or absence of OVA survival (staining with the live marker DAPI)",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "DICER-KO B cells were co-cultured for 24 hours with OTII-derived T cells in the presence or absence of OVA. Flow cytometry analysis of B lymphocytes co-cultured with OT-II isolated T cells in the presence or absence of OVA apoptosis (cleaved Caspase-3 expression) 24h, 48h and 72h after IS formation.",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "CD4+ T and DICER-KO B cells were co-cultured for 24 hours with or without OVA, and flow-cytometry sorted B cells were analyzed by small RNA next generation sequencing (NGS). Heat map showing microRNAs significantly upregulated in B cells after co-culture with T cells in the presence of OVA. Data are from 3 independent experiments (samples 1-3), and only microRNAs with an adjusted P-value < 0.02 are shown. Fold increase in the B cell content of upregulated microRNAs in the presence of OVA; *P<0.05, **P<0.01, ***P<0.001.",
    "ncbi_link": "DICER: 192119"
  },
  {
    "caption": "Quantitative real-time PCR of upregulated microRNAs after co-culture of OT-II derived CD4+ T cells with DICER-KO B cells activated with LPS+IL-4 Bars represent the mean ± SEM of at least three independent experiments and data were obtained by the 2-∆∆Ct method using Biogazelle software. Results are expressed as a proportion of the microRNA expression in non-OVA containing co-cultures, with normalization to the small nucleolar RNAs RNU1A1 and RNU5G.",
    "ncbi_link": "DICER: 192119
RNU1A1: 19842
RNU5G: 97418"
  },
  {
    "caption": "Quantitative real-time PCR of upregulated microRNAs after co-culture of OT-II derived CD4+ T cells with DICER-KO B cells activated with CD40+IgM Bars represent the mean ± SEM of at least three independent experiments and data were obtained by the 2-∆∆Ct method using Biogazelle software. Results are expressed as a proportion of the microRNA expression in non-OVA containing co-cultures, with normalization to the small nucleolar RNAs RNU1A1 and RNU5G.",
    "ncbi_link": "DICER: 192119
RNU1A1: 19842
RNU5G: 97418"
  },
  {
    "caption": "Quantitative real-time PCR showing the expression of down-modulated mRNA targets upon IS formation between OT-II CD4+ T cells and DICER-KO B cells pre-activated with LPS+IL-4 Results are the means ± SEM of at least four independent experiments and are expressed as a proportion of mRNA expression in the non-OVA condition, with normalization to GAPDH.",
    "ncbi_link": "GAPDH: 
DICER: 192119"
  },
  {
    "caption": "Quantitative real-time PCR showing the expression of down-modulated mRNA targets upon IS formation between OT-II CD4+ T cells and DICER-KO B cells pre-activated with CD40+IgM Results are the means ± SEM of at least four independent experiments and are expressed as a proportion of mRNA expression in the non-OVA condition, with normalization to GAPDH.",
    "ncbi_link": "GAPDH: 
DICER: 192119"
  },
  {
    "caption": "Fluorescently tagged mimics of the microRNAs mmu-miR-20a-5p, mmu-miR-25-3p and mmu-miR-155-3p were nucleofected into activated B lymphocytes from C57/BL6 mice. Quantitative real-time PCR showing expression of nucleofected microRNA mimics in FACS-sorted FAM+ B cells with normalization to RNU1A1 and RNU5G",
    "ncbi_link": "mmu-miR-155-3p: 387173
mmu-miR-20a-5p: 387139
mmu-miR-25-3p: 723926
RNU1A1: 19842
RNU5G: 97418"
  },
  {
    "caption": "Fluorescently tagged mimics of the microRNAs mmu-miR-20a-5p, mmu-miR-25-3p and mmu-miR-155-3p were nucleofected into activated B lymphocytes from C57/BL6 mice. Quantitative real-time PCR showing expression of Bcl2l11 and Pten mRNA targets in mimic-nucleofected B cells with normalization to GAPDH",
    "ncbi_link": "GAPDH: 
Bcl2l11: 12125
mmu-miR-155-3p: 387173
mmu-miR-20a-5p: 387139
mmu-miR-25-3p: 723926
Pten: 19211"
  },
  {
    "caption": "Quantitative real-time PCR (RNU1A1 and RNU5G- normalized) showing blockade of microRNA transfer from CD4+ T cells pre-treated with siRNA targeting the exosome secretion mediator Rab27. Bar charts represent the mean values ± SEM of at least 4 independent experiments.",
    "ncbi_link": "Rab27: 11891
RNU1A1: 19842
RNU5G: 97418"
  },
  {
    "caption": "Quantitative real-time PCR showing mRNA target down-modulation after IS formation between DICER-KO B cells and CD4+ T cells nucleofected with either siRab27 or scrambled control siRNA, with normalization to GAPDH. Bar charts represent the mean values ± SEM of at least 4 independent experiments.",
    "ncbi_link": "GAPDH: 
DICER: 192119
Rab27: 11891"
  },
  {
    "caption": "Kymograph of the lamellar activity of WASP-deficient cells that lack actin foci.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "Foci -deficient cells display poor traction forces in their synapse. WT or WASP-/- T cells were incubated on polyacrylamide substrates covalently functionalized with anti-CD3 and ICAM1, and traction force measurements were carried out as described in 'Methods'. The images in the right show traction force maps without (left panels) or with (right panels) force vectors. p value, **P<0.005 as determined by using Mann-Whitney two-tailed test between populations of cells within the same experiment, n = 9 and 11.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "SIM imaging of WT or WASP-/- T cells activated by APS for 5'. The graphs show quantification of actin foci (derived from phalloidin staining), pCasL and talin levels in the synapse normalized to the 'WT' mean value in each case (Middle graph; in the case of foci, n= 63 for WT and 86 for WASP-/-; in the case of pCasL n= 63 for WT and 78 for WASP-/-; in the case of Talin, n= 59 for WT and 73 for WASP-/-; in the case of AR, n= 46 for WT and 42 for WASP-/-); right graph shows AR measurement. ***P <0.0001; p value for talin *P=0.07, as determined by using Mann-Whitney two-tailed test between populations of cells within the same experiment.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "Human WAS patient CD4+T cells- APC conjugates display synapse symmetry defects similar to those observed in mouse WASP-/- CD4+ T cells. CD4+T cells purified from healthy controls or WAS patients were incubated with superantigen loaded HUVEC cells for 5' (APC; see 'Methods') and imaged using confocal microscopy. Each image represents a maximum intensity projection of the synaptic area. Graph in the middle shows values normalized to the mean value of the 'Healthy' case. In the case of 'actin' and 'actin foci', n= 87 for healthy and n= 63 for WAS; in the case of pCasL, n=56 for healthy and n= 21 for WAS; for 'AR' graph, n= 88 for healthy and n= 63 for WAS case. P values; ***P <0.001; n.s. P=0.09, as determined by using Mann-Whitney two-tailed test between populations of cells within the same experiment.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "Simulation of T cell IS F-actin behavior and resultant mechanical tension incorporating the differential dynamics and positioning of foci and lamella across the synaptic interface, using Brownian dynamics equation with no inertia (see 'Methods'). The images show simulation snapshots at the beginning (0 min; soon after the attachment and spreading of T cells on the substrates) and the end of the simulations for the three IS cases - with persistent foci (WT, left most panels), with no foci (WASP-/-, middle right panels), and with WASP and consequently foci downregulated after a period of synapse maturation (WT transitional). The colors in the images indicate myosin II motor (pseudocolored teal), F-actin crosslinking proteins (pseudocolored yellow), and the F-actin filaments (pseudocolored blue for the low tension and the red for thigh tension actin filaments); middle left image panels show the distribution of the aforementioned proteins at individual foci site at a higher magnification.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "Ultrastructural visualization of detergent extracted WT and WASP-/- T cell synaptic cytoskeleton using platinum replica electron microscopy (top images). Each image shows individual synapse, dark zone in the middle of the synapse represents cell nucleus. Scale bar, 2.5μm. The bottom left micrograph is the magnified inset from WT synapse and shows actin foci (identified as globular cluster of short filaments in the inset, marked with arrows)-dependent interconnected cytoskeletal architecture that is associated with synapse symmetry as predicted in the model, and is lacking in the WASP-/- cell synapse (bottom right micrograph- magnified inset from WASP-/- synapse). Scale bars, 1μm.This experiment was repeated at least twice with similar results.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "T cells were activated using Alexa568-2C11 and ICAM1 reconstituted lipid bilayers for 5 min, fixed, stained with phalloidin and imaged using SIM. In the graph, n= 50 for WT and 61 for WASP-/-, P value, P***<0.0001, obtained using Mann-Whitney two-tailed test. The graphs in (B) show synaptic levels of indicated proteins, normalized to the mean levels of '+WASP' in each case. For the left graph, n= 48, 46, 52, 46 respectively, and p value, P *= 0.03. For the right graph, n= 50 for WT and n= 61 for WASP-/- in 'Actin', 'Foci', as well as 'pCasL' cases. P values P*** <0.0001, obtained using Mann-Whitney two-tailed test.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "Synapse breaking behavior of T cells on hydrogels of indicated stiffness, covalently conjugated with 2C11 and ICAM1. These experiments were repeated at least thrice with similar results. In the left graph, n for WT= 14, for WASP-/-, n= 19; P**= 0.0015; in the graph on the right, n for WT= 40, n for WASP-/-= 36, P***= 0.0006, as assessed using Mann-Whitney two-tailed test.",
    "ncbi_link": "WASP: 22376"
  },
  {
    "caption": "(A) Glu529 (purple) forms a hydrogen bond with the C2-amino group of the primer terminal templating 8-oxo-dG (orange) in the anti-conformation. (B) This interaction is abolished when 8-oxo-dG (orange) adopts the syn-conformation. An overlay with the 8-oxo-dG(anti)-containing structure reveals that Glu529 (black) would likely clash (red-dotted line) with the C8-carbonyl of 8-oxo-dG(syn). Repositioning of Glu529 (purple) places the side chain 4.5 Å away from the C8-carbonyl. (C) Comparison of catalytic efficiencies for extension past an 8-oxo-dG(anti):dC, 8-oxo-dG(syn):dA and dG:dC base pairs at the primer terminus using WT and E529A Pol λ.",
    "ncbi_link": "Pol λ: 27343"
  },
  {
    "caption": "H&E staining of adult head sections of (A) repo>GFP.nls and (B) repo>Shits1 at 29°C for 3 days. Lamina degeneration was identified as vacuoles in (B). Cryosection of adult (C) repo>H2B-RFP exhibited the expression of the nuclear red fluorescent protein (RFP) in the glia (epithelialglialnucleus: arrowhead) and (D) repo>Shits1 at 28°C for 12 days. Vacuoles were identified in the lamina neuropile (D). Epithelial (arrowhead) (E), marginal (arrow) and distal satellite (arrowhead) glianuclei (F) are labeled by HisCl-GAL4 and NP2109-GAL4, respectively. Note that HisCl-GAL4 is not expressed in all epithelialglia. (G, H) Weak lamina vacuolization was identified in HisCl>Shits1 (G, 0.92%) and NP2109>Shits1 (H, 1.46%) at 29°C for 14 days. (I, J) A single MARCMglia clone (GFP, green) expressed Shits1 at 21°C (I) and 29°C (J). (J) A vacuole occurred within a glial clone. DAPI (white) stains the nuclei (C, D, and G-J). (K) The percentage of the vacuole area in the lamina of the repo>Shits1flies at 28°C progressively increased. n indicated in each column. P-values were calculated using one-way ANOVA with Bonferroni's post-test. (L) When repo>Shits1flies were shifted to 28°C for 12 days and then shifted to 17°C for 9 additional days, the vacuolization was not alleviated. P-values were calculated using one-way ANOVA with Tukey's post-test. n indicated in each column.",
    "ncbi_link": "GAL4: 
NP2109: 
H2B: 8349
Shi: 45928"
  },
  {
    "caption": "(A-E) Horizontal sections of the adult head lamina cartridge. (A) In repo>GFP.nls flies, two lamina neurons L1, L2 axons (L) and R1-6 axons (blue area) were surrounded by the electron-dense cytoplasm of the epithelial glia (G). The section was examined at three different depths, and the size of a single cartridge is not significantly different at different depths. (B-D) repo>Shits1 adults maintained at 29°C for 4 days. Axons were enlarged but intact. A large number of small and medium vacuoles were identified in the epithelial glia. (C) Small vacuoles in the glia that contained a double-membrane structure (arrowhead). (C') Higher magnification of the boxed area in (C). (D) A double-membrane autophagosome-like structure (arrowhead) in the glialcytoplasm. (E) In repots>DERDN adults maintained at 29°C for 2 days, large vacuoles were identified in between the lamina cartridges. N: glialnuclei. (E') Higher magnification of the boxed area in (E), which shows autophagosome-like vesicles (arrowhead) in the gliacytoplasm.",
    "ncbi_link": "DER: 37455
Shi: 45928"
  },
  {
    "caption": "(A) Rh1>lacZ+H2B-RFP exhibited nuclearRFP expression in the R1-6 photoreceptors (red). (B) Rh1>lacZ+Shits1 maintained at 29°C for 14 days resulted in lamina vacuolization. (C) Pan-Rh7>H2B-RFP exhibited expression in R7 (arrow) and R8 (arrowhead) (red). (D) Pan-Rh7>Shits1 incubated at 29°C for 14 days did not exhibit lamina degeneration. (E) Lamina monopolar (L) neurons (red) were selectively labeled by the Ln-GAL4 driven H2B-RFP with repo-GAL80. (F) Ln>Shits1, repoGAL80 shifted to 29°C for 14 days did not exhibit lamina degeneration. (G) R1-6 photoreceptors were killed in Rh1ts>lacZ+Hid shifted to 29°C for 14 days. Rh1ts indicates tubGAL80ts; Rh1-GAL4. Degeneration was induced in the lamina in addition to the retina. (H) rdgC306/+ mutant exposed to constant light for 14 days exhibited degeneration in the retina, as well as the lamina. DAPI: nuclei (white in A-H). (I, K) Rh1>lacZ+Shits1 at 29°C for 4 days exhibited vacuoles in the electron dense cytoplasm of epithelialglia or near the glianucleus. Arrow: vacuole with internal debris. Arrowhead: large vacuole. (J) Lamina cartridge of Rh1>lacZ+H2B-RFP. N indicates glialnuclei. (L) The percentage of the vacuole area in the lamina at 29°C for 14 days was examined. All P-values were calculated using one-way ANOVA with Tukey's post-test. Scale bar: 20 μm.",
    "ncbi_link": "GAL4: 
GAL80: 
lacZ: 
H2B: 8349
Rh1: 42367
rdgC: 40224
Rh7: 39389
Shi: 45928"
  },
  {
    "caption": "(A) repots>Shits1+H2B-RFP, (B) repots>Shits1+Egfrλtop and (C) repots>Shits1+RlSem incubated for 12 days at 28°C. (D) repots>DERDN for 7 days at 28°C. (E) Epithelial glia MARCM clone and (F) Egfrco mutant glia MARCM clone (labeled with Tomato, green). The penetrance is indicated as the number of samples with vacuoles over the total number of samples. DAPI: nuclei (white in A-F). (G) Percentage of vacuole area in the lamina neuropile of (A-D). The P-values were calculated using one-way ANOVA with Dunnett's post-test. (H) Percentage of vacuole area in the lamina of repots>Shits1 flies in the indicated genetic background. The adults were shifted to 28°C for 12 days. The P-values were calculated using one-way ANOVA with Tukey's post-test. Scale bar: 20 μm.",
    "ncbi_link": "DER: 37455
Egfr: 37455
H2B: 8349
Rl: 3354888
Shi: 45928"
  },
  {
    "caption": "(A, A') Anti-Spitz (red) immunostaining of w1118 adult head. Spitz can be detected in the retina and lamina. (B, B') The full-length transmembrane form of Spitz-GFP (mSpi, green) expressed in the retina in GMR>mSpiGFP flies was predominantly identified in the photoreceptor soma and terminally localized in the lamina cartridge. mSpitz-GFP requires processing by Rho and Star to become a secreted form. Overexpressed mSpitzGFP has been demonstrated to be retained in the perinuclear ER even in the presence of endogenous Rho/Star [56] (C) Knockdown of both EGFR ligands Spi and Krn in R1-6 photoreceptors in Rh1>Dcr2+Spi-RNAi+Krn-RNAi and (D) blockade of Spi processing in Rh1>lacZ+iRhom exhibited lamina degeneration after shifting to 29°C for 14 days. (E-E') Lamina degeneration in whole eye rho7M43ru1 double mutant clones at 28°C for 12 days. The clone is labeled by DsRed (red). (F) Spi secretion is inhibited in Rh1>lacZ+Rab11S25N. (G) The percentages of the vacuole areas of (C, D, F) in lamina at 29°C for 14 days were examined. All P-values were calculated using one-way ANOVA with Tukey's post-test. DAPI: nuclei (white in A', B', C-F). Scale bar: 20 μm.",
    "ncbi_link": "lacZ: 
Dcr2: 36993
EGFR: 37455
Krn: 326198
Rh1: 42367
Rab11: 42501
Rho: 38168
rho: 38168
ru: 44856
Star: 33281
Spi: 35253
Spitz: 35253"
  },
  {
    "caption": "(A, A') Anti-Spitz detected Spitz (magenta) colocalizing (arrowhead) with epithelialgliacytoplasm marked by anti-Black (green). Scale bar: 5 μm. (B-B') EGFR reporter pointed-lacZ (pnt-lacZ) exhibited expression in the epithelial (arrow) and marginal glia (arrowhead). (C, C') Dominant-negative form of EGFR (DERDN) expressed in glia at 28°C for 3 days inhibited pnt-lacZ expression. (D, D') pnt-laZ expression was lost in Shits-expressing glia at 28°C for 3 days. (E, E') The knockdown of Spi in R1-6 photoreceptors at 28°C for 12 days also inhibited pnt-lacZ expression in the glia. The penetrances of (B-E) are shown in the upper right corner of each panel. DAPI: nuclei (white in B'-E'). Scale bar: 20 μm.",
    "ncbi_link": "lacZ: 
DER: 37455
EGFR: 37455
Shi: 45928
Spi: 35253
Spitz: 35253"
  },
  {
    "caption": "(A-C) Immunostaining of TUNEL assay (red), active Caspase-3 (magenta, A'-C') and Repo (green, A\"-C\"). (A) GMR-wIR; repots>lacZ. (B) GMR-wIR; repots>Shits1. (C) GMR-wIR; repots>DERDN. GMR-wIR was used to reduce the autofluorescence of the eye pigments. Scale bar: 20 μm. (D-F) The in vivo fluorescent sensor of caspase activity (Apoliner) indicated there was no active caspase activity in the glia. (D) repots>Apoliner+lacZ. (E) repots>Apoliner+Shits1. (F) repots>Apoliner+DERDN. All adults were shifted to 28°C for 5 days. nls-GFP (green, D-F); merge of GFP (green) and mRFP (red) in (D'-F'); merge of nls-GFP and DAPI (magenta) in (D\"-F\"). Scale bar: 10 μm. (G) Percentage of vacuole area in the lamina in repots>Shits1flies that coexpressed the anti-apoptotic factors P35 and Diap1. The adults were shifted to 28°C for 21 days. The P-values were calculated using one-way ANOVA with Tukey's post-test. (H) The cell number of the epithelialglia was not reduced in the vacuolated lamina. The numbers of epithelial glia in the lamina of repo>H2B-RFP and repo>H2B-RFP+Shits1 female adults incubated at 28°C for 14 days were examined by counting the nuclear RFP at the epithelial layer from the entire Z-stacks of confocal images. P-values were calculated via Mann-Whitney tests.",
    "ncbi_link": "Apoliner: 
lacZ: 
DER: 37455
H2B: 8349
H2B: Q16778///8349
Shi: 45928"
  },
  {
    "caption": "In repots>GFP-LC3+DERDN shifted to 28°C, the GFP signal (green) was weak on day 1 (A-A\") and progressively increased on days 2 (B-B\") and 3 (C-C\") and colocalized with Ref(2)P (magenta). (D) Ref(2)P (magenta) accumulated within the Egfrco mutant MARCM clone (green). The double-tagged GFP-mCherry-Atg8a is used to distinguish the autophagosomes (GFP and mCherry, yellow) and autolysosomes (mCherry, red) in autophagic flux. (E) In repots>GFP-mCherry-Atg8a+dAtg1, autophagosomes (arrowhead) and autolysosomes (arrow) were induced in the glia with normal autophagic flux. (F) repots>GFP-mCherry-Atg8a. (G) repots>GFP-mCherry-Atg8a+Shits1. Epithelialglial nuclei are indicated (arrow). (H) repots>GFP-mCherry-Atg8a+DERDN. The adults were shifted to 28°C for 3 days. GFP: green (E-H); mCherry: red (E'-H'); merge (E\"-H\"). Scale bar: 10 μm.",
    "ncbi_link": "Atg1: 39454
Atg8a: 32001
DER: 37455
Egfr: 37455
LC3: 440738///81631///84557
Shi: 45928"
  },
  {
    "caption": "(A-C) repots>GFP-LAMP1. (D-F) repots>GFP-LAMP1+Shits1. (G-I) repots>GFP-LAMP1+DERDN. Adults were incubated at 28°C for 12 h (A, D, G), 24 h (B, E, H), and 48 h (C, F, I), respectively. The GFP-LAMP1 signal (green) was induced at 12 h and progressively enhanced in (D-F) and (G-I). (J) repots>Rab7-mCherry+H2B-RFP. (K) repots>Rab7-mCherry+Shits1. (L) repots>Rab7-mCherry+DERDN. The adults were shifted to 28°C for 2 days. Rab7-mCherry puncta (red) were increased in (K, L). DAPI: nuclei (white in J'-L'). Scale bar: 20 μm.",
    "ncbi_link": "DER: 37455
H2B: 8349
LAMP1: 3916
Rab7: 42841
Shi: 45928"
  },
  {
    "caption": "(A) repots>Rab5S43N. (B) repots>Rab7T22N. (C) repots>Rab11S25N. (D-H) MARCM clones labeled by RFP or GFP (green) of control (D), Rab52 (E), α-Ada3 (F), HrsD28 (G), Rab7KO (H), dor8 (I) and carΔ146 (J). The penetrance (number of samples with vacuole over the number of samples examined) is indicated in each panel. Adults of all genotypes were incubated at 28°C for 14 days. DAPI: nuclei (white in A-J). Scale bar: 20 μm. (K) The percentage of the vacuole area in (A-C) was summarized. Adults of these genotypes were incubated at 28°C for 12 days. P-values were calculated using Kruskal-Wallis with Dunn's post-tests.",
    "ncbi_link": "Ada: 33211
car: 32947
dor: 38543
Hrs: 33458
Rab11: 42501
Rab5: 33418
Rab7: 42841"
  },
  {
    "caption": "repots>DERDN was coexpressed with (A) H2B-RFP, (B) Dorwt, (C) Dor-RNAi, (D) H2B-RFP, (E) Car, (F) Car-RNAi, (G) lacZ, (H) Car-RNAi+Dor-RNAi and (I) Car+Dorwt. The autophagy reporter Ref(2)P (green) was stained (G'-H'). Scale bar: 20 μm. (J, K, L) The percentages of the vacuole areas in the lamina of (A-C, D-F, G-I) were summarized, respectively. The adults were shifted to 28°C for 7 days. DAPI: nuclei (white in A-I). All P-values were calculated using Kruskal-Wallis tests with Dunn's post-tests.",
    "ncbi_link": "lacZ: 
Car: 32947
Dor: 38543
DER: 37455"
  },
  {
    "caption": "(B) Quantification of embryos that expressing the ZGA reporter (MERVL::tdTomato) after injection with a siRNA-repressor or mRNA-inducer. N, the total number of embryos analyzed for each condition. Error bars, mean ± S.D.; n = 3 biological replicates per group.",
    "ncbi_link": "tdTomato: 
MERVL: 27282"
  },
  {
    "caption": "(C) Representative fluorescence image of SCNT embryos derived by different methods. The SCNT embryos produced by transfer of MERVL::tdTomato cumulus cells (B6D2F1 background) into WT enucleated oocytes. n = 3 biological replicates per group. Scale bar, 100 μm.",
    "ncbi_link": "tdTomato: 
MERVL: 27282"
  },
  {
    "caption": "(G) Preimplantation development of SCNT embryos. The percentage of embryos reaching each indicated stage is shown. The D-SCNT embryos produced by transfer of dox-Dux cumulus cell (B6D2F1 background) into WT enucleated oocytes (B6D2F1 background). Error bars, mean ± S.D.; n = 3 biological replicates per group. Scale bar, 100 μm.",
    "ncbi_link": "Dux: 664783"
  },
  {
    "caption": "(E) RT-qPCR analysis of select ZGA-related genes in dox-untreated D-CiPSCs and canonical CiPSCs at passage 1. The value in CiPSCs was set as 1, and data shown are mean expression values relative to GAPDH. Error bars, mean ± S.E.M.; n = 3 biological replicates per group; ***P < 0.001 by two-tailed Student's t-test.",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "(J) Bisulfite sequencing analysis of demethylation of Oct4 and Nanog promoters in D-CiPSCs or canonical CiPSCs. Filled and empty squares represent methylated and unmethylated CpGs, respectively.",
    "ncbi_link": "Nanog: 71950
Oct4: 18999"
  },
  {
    "caption": "(B) Dual excitation (550/488 nm) of mt-mKeima transfected-Huh7 cells shows red fluorescence indicating mitophagy with DFP treatment at 24 h and green fluorescence without DFP treatment. Scale bar: 10 μm.",
    "ncbi_link": "mt-mKeima: "
  },
  {
    "caption": "(C) The high ratio signal cells were quantified by flow cytometry with dual excitation of mt-mKeima at 633/488 nm for untreated (left panel) and DFP-treated (24 h, right panel) Huh7 cells.",
    "ncbi_link": "mt-mKeima: "
  },
  {
    "caption": "(D) Untreated Huh7 cells or those treated with DFP (10 μM), DFX (10 μM) or DFO (10 μM) were quantified for mitophagy using mt-mKeima transfection and FACS analysis (n=4, biological replicates). A high signal (633/488) area/ cell area indicates the proportion of cells undergoing mitophagy. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. **: P<0.01.",
    "ncbi_link": "mt-mKeima: "
  },
  {
    "caption": "(F) Quantification of mitophagy using mt-mKeima transfection and FACS analysis for Huh7 cells treated with DFP (0, 0.01. 0.5 or 1.0 mM as indicated) in the absence or presence of bafilomycin (n=4, biological replicates). The central horizontal bar and the error bards indicate mean ± SD. *: P<0.05, **: P<0.01.",
    "ncbi_link": "mt-mKeima: "
  },
  {
    "caption": "(D) The mRNA expression of FTMT in Huh7 cells was quantified by real-time RT-PCR before and after DFP (1.0 mM) treatment (n=4, biological replicates). The expression of FTMT mRNA level was normalized to GAPDH mRNA. The central horizontal bar and the error bards indicate mean ± SD. Two sample t test was used for statistical analysis. **: P<0.01.",
    "ncbi_link": "GAPDH: 
FTMT: 94033"
  },
  {
    "caption": "(E) The mRNA expression of FTMT in Huh7 cells was quantified by real-time RT-PCR before DFP (1.0 mM) treatment and 3, 6, 12, and 24 h after DFP treatment (n=5, biological replicates). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. **: P<0.01, ***: P<0.001.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(F) DNA-binding activity of six transcription factors (specific protein 1 [SP1], cAMP response element binding protein [CREB], Ying yang 1 [YY1], GATA2, forkhead box protein A1 [FoxA1] and CCAAT-enhancer-binding protein β [ C/EBPβ]) to the FTMT promoter region was compared by chromatin immunoprecipitation before and after DFP (1.0 mM) treatment in Huh7 cells (n=4, biological replicates). The central horizontal bar and the error bards indicate mean ± SD. Two sample t test was used for statistical analysis. *: P<0.05.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(G) The DNA-binding activity of SP1 to the FTMT promoter region was assayed by chromatin immunoprecipitation following treatment with DFP (0, 0.01, 0.1, 0.5 or 1.0 mM) as indicated in Huh7 cells (n=4, biological replicates). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(H) FTMT mRNA expression was quantified for Huh7 cells by real-time RT-PCR before and after DFP (1.0 mM) treatment with or without SP1 knockdown by siRNA (n=5, biological replicates). mRNA expression of FTMT level was normalized to GAPDH. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. NC: negative control siRNA, **: P<0.01.",
    "ncbi_link": "GAPDH: 
FTMT: 94033
SP1: 6667"
  },
  {
    "caption": "(K) Immunoblots for FTMT, HIF1α and SP1 using the mitochondrial fraction lysate and whole cell lysate of Huh7 cells before and after DFP (1.0 mM) treatment with or without HIF1α or SP1 knockdown by siRNA. HSP60 and β-actin were used as loading controls for the mitochondrial fraction and whole cell lysates, respectively.",
    "ncbi_link": "HIF1α: 3091
SP1: 6667"
  },
  {
    "caption": "(A) Immunoblots for mitochondrial ferritin (FTMT) with HSP60 as the loading control using the mitochondrial fraction of Huh7 cells and HepG2 cells (upper panels) and the quantification of mitophagy using mt-mKeima transfection and FACS analysis (n=4, biological replicates) (lower panels) before and after DFP (1.0 mM) treatment with or without FTMT knockdown by siRNA. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. NC: negative control siRNA, **: P<0.01.",
    "ncbi_link": "mt-mKeima: 
FTMT: 94033"
  },
  {
    "caption": "(B) Immunofluorescence staining for LC3 (red), the mitochondrial marker Tom20 (green) and FTMT (blue) in Huh7 cells before and after DFP (1.0 mM) treatment with or without FTMT knockdown by siRNA. FTMT colocalize with LC3 at the mitochondria (white puncta indicated by arrows). Boxed areas are enlarged below. Scale bar: 5 μm",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(C) Immunoblots for mitochondrial ferritin (FTMT) following FTMT knockdown in the absence or presence of DFP using the mitochondrial fraction of Huh7 cells and those transfected with FTMT siRNA-resistant FTMT (left panel). HSP60 as the loading control. Those cells were subjected to the quantification of mitophagy using mt-mKeima transfection and FACS analysis before and after DFP (1.0 mM) treatment (n=5, biological replicates) (right panel). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. ***: P<0.001.",
    "ncbi_link": "mt-mKeima: 
FTMT: 94033"
  },
  {
    "caption": "(D) Super resolution images of immunofluorescence staining for LC3 (red), FTMT (green) and Tom20 (blue) in FTMT knockdown-Huh7 cells transfected with FTMT-GFP or FTMT siRNA-resistant FTMT-GFP before and after DFP (1.0 mM) treatment. White arrows indicate colocalization of LC3, FTMT, and Tom20.",
    "ncbi_link": "GFP: 
FTMT: 94033"
  },
  {
    "caption": "(F) Extracted proteins from Huh7 cells expressing the recombinant proteins as indicated were mixed with anti-GFP-coupled magnetic beads and immunoblotted with anti-mCherry and anti-GFP antibodies. Co-immunoprecipitation revealed a specific interaction of NCOA4-mCherry with FTMT-GFP or FTMTD57A-GFP, which has a substitution of alanine (A) for aspartic acid (D) at position 57 in the FTMT mitochondrial leader sequence (lanes 1 and 3).",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(G) Following DFP (1.0 mM) or ammonium iron sulfate (FAS) treatment as indicated, extracted proteins from Huh7 cells expressing FTMT-GFP and NCOA4-mCherry were mixed with anti-GFP-coupled magnetic beads and immunoblotted with anti-mCherry and anti-GFP antibodies.",
    "ncbi_link": "GFP: 
mCherry: 
FTMT: 94033
NCOA4: 8031"
  },
  {
    "caption": "(C) Immunofluorescence staining for FTMT-GFP (green) and LC3 (red) in Huh7 cells transfected with FTMT-GFP. The proportion of colocalization was quantified for four randomly selected areas (technical replicates) using ImageJ software version 1.46 (NIH, Bethesda, MD). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. **: P<0.01.",
    "ncbi_link": "GFP.: 
FTMT: 94033"
  },
  {
    "caption": "(D) Immunofluorescence staining for Ferritin-GFP heavy chain (FTH1) (green) and LC3 (red) in Huh7 cells transfected with FTH1-GFP. The proportion of colocalization was quantified as described in (C). *: P<0.05, **: P<0.01.",
    "ncbi_link": "GFP.: 
FTH1: 2495"
  },
  {
    "caption": "(E) Immunoblots for the precursor form and processed form of FTMT-GFP, endogenous FTMT, NCOA4, LC3, and Tom20 using the mitochondrial fractions of Huh7 cells expressing FTMT-GFP with or without digestion with proteinase K in the presence or absence of DFP. mtHSP70 was used as the loading control.",
    "ncbi_link": "GFP: 
FTMT: 94033"
  },
  {
    "caption": "(B) Immunofluorescence staining for the polarized mitochondria (red), Tom20 (blue), LC3 (blue), and FTMTD57A (green) using Huh7 cells expressing FTMTD57A. Boxed areas are enlarged on the right. The white puncta in overlaid pictures indicate the colocalization of the polarized mitochondria, Tom20 and FTMTD57A or the colocalization of the polarized mitochondria, FTMTD57A, and LC3. Scale bar: 10 μm, and 5 μm in enlarged images.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(A) Immunoblots for FTMT, frataxin, mitoferrin, HSP60, FTH1 and TfR using the hepatic mitochondrial fraction lysate and whole liver lysate in control (C57BL/6J) mice and STAM mice treated with DFP (0, 0.0375, or 0.075 mg/g body weight) (n=6). The expression of FTMT, frataxin, mitoferrin, FTH1, and TfR were normalized to HSP60 or β-actin, respectively. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01. (B) The mean number of mitophagosome-like structures/100 μm2 from four randomly selected areas in the livers of DFP (0.075 mg/g body weight)-administered mice were compared between control and FTMT siRNA-treated groups for STAM mice (n=6) and DMBA + HFD mice (n=6). The central horizontal bar and the error bards indicate mean ± SD. Two sample t test was used for statistical analysis. NC: negative control siRNA, *: P<0.05. ",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(C) Frozen liver sections of DFP (0.075 mg/g body weight)-administered mice (STAM mice and DMBA + HFD) with or without FTMT knockdown were stained with dihydroethidium. Red fluorescence indicates the ROS production. Scale bar: 100 μm. siNC: negative control siRNA.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "(D, E) STAM mice (D) were fed a high-fat diet without DFP treatment or orally administered with 0.075 mg/g body weight of DFP from the age of 4 weeks, injected with FTMT siRNA (10 μl/g body weight) or negative control siRNA through the tail vein every 2 weeks for 8 weeks prior to sacrifice, and followed until 16 weeks of age (n=6). DMBA + HFD mice (E) were fed a high-fat diet, treated with DFP and siRNA in the same manner with STAM mice, and followed until 30 weeks of age (n=6). The number and maximum size of liver tumors were compared among the three groups (control without DFP, negative control siRNA, and FTMT siRNA with DFP). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01. Representative liver images are shown in the upper panel. Scale bar: 1 cm.",
    "ncbi_link": "FTMT: 94033"
  },
  {
    "caption": "B Interaction  of Atg18 with retromer  subunits. Genomically tagged  yomCherry-fusions of each retromer  subunit were expressed in SEY6210 atg18∆, atg21∆, hsv2∆ cells, together with a plasmid expressing  Atg18HA3yEGFP. Cell lysates were subjected to immunoprecipitation  using RFP-Trap magnetic beads and analyzed by SDS-PAGE and Western blotting against the indicated proteins.",
    "ncbi_link": "HA3: 
yEGFP: 
yomCherry: 
atg18: 850577
Atg18: 850577
atg21: 856004
hsv2: 853138"
  },
  {
    "caption": "D Atg18-Vps35 interaction. Genomically tagged Vps35yomCherry was pulled down from lysates of SEY6210   WT or SEY6210 vps26∆ strains carrying genomically tagged Atg18HA3yEGFP. Adsorbed proteins were analyzed by  SDS-PAGE and Western blotting using the antibodies indicated in brackets. E Signals from the blots  in d were quantified on an infrared fluorescence scanner and normalized to the amount of  pulled-down Vps35yomCherry. n=3 independent experiments were analyzed using an unpaired Student's t-test. Bars represent the mean and errors bars the SEM. *** P < 0.001.",
    "ncbi_link": "HA3: 
yEGFP: 
yomCherry: 
Atg18: 850577
vps26: 853393
Vps35: 853287"
  },
  {
    "caption": "F Atg18-Vps26 interaction. Genomically tagged Vps26yomCherry was pulled down from lysates of SEY6210  WT, SEY6210 vps35∆ or SEY6210 vps29∆ strains carrying genomically tagged  Atg18HA3yEGFP. Adsorbed proteins were analyzed as in D. G Proteins from F were quantified as in E. n=3 independent experiments were analyzed using an unpaired Student's t-test. Bars represent the mean and errors bars the SEM. *** p < 0.001).",
    "ncbi_link": "HA3: 
yEGFP: 
yomCherry: 
Atg18: 850577
Vps26: 853393
vps29: 856403
vps35: 853287"
  },
  {
    "caption": "A Vps17  labilizes the Atg18-Vps26 interaction. Wildtype or vps17∆ cells expressing ATG18HA3-yEGFP from a centromeric  plasmid were logarithmically grown in YPD. Genomically tagged Vps26yomCherry was  pulled down from whole-cell extracts and analyzed for associated Atg18HA3-yEGFP by SDS-PAGE  and Western blotting. Glucose-6-phosphate dehydrogenase (Zwf1) serves as a loading control. The intensity of the interacting Atg18HA3-yEGFP was quantified on a LICOR fluorescence imager and normalized to the amount of  Vps26yomCherry. Values of the wildtype interaction  were used as the reference and set to 1. n = 4 independent experiments were analyzed using an unpaired Student's t-test. Bars represent the mean and errors bars the SEM, ** p < 0.01)",
    "ncbi_link": "HA3: 
yEGFP: 
yomCherry: 
ATG18: 850577
Vps26: 853393
Vps17: 854300
vps17: 854300"
  },
  {
    "caption": "B Epistasis of ATG18  and retromer  genes concerning vacuolar morphology. The indicated cells were logarithmically grown in YPD medium, stained  with FM4-64 and  calcofluor white C Quantification of vacuole morphology. The number of vacuoles  per cell was measured in the cells from B. The graph shows the fractions of cells displaying the indicated numbers of  vacuolar vesicles (n = 3 biological experiments with at least 100 cells per condition and experiment were analyzed using an unpaired Student's t-test. Bars represent the mean and errors bars the SEM. ** p < 0.01",
    "ncbi_link": "ATG18: 850577"
  },
  {
    "caption": "C  Pull-down. Cells (SEY6210 atg18∆, atg21∆) expressing genomically tagged Vps26yomCherry  and the indicated Atg18HA3-yEGFP variants were logarithmically grown in SC-URA media.  Vps26yomCherry was pulled down from whole-cell extracts with RFP-trap magnetic beads and analyzed by  SDS-PAGE and Western blotting against the indicated proteins. Bands were quantified on a LICOR fluorescence imager. Signals of Atg18HA3yEGFP were normalized relative to those of Vps26yomCherry. Vps1 served as a loading control. n = 3 independent replicates. Data were subjected to an unpaired t-test. Bars represent the mean and errors bars the SEM, *** P < 0.001).",
    "ncbi_link": "HA3: 
yEGFP: 
yomCherry: 
atg18: 850577
Atg18: 850577
atg21: 856004
Vps26: 853393"
  },
  {
    "caption": "A, Effect of Atg18T56E on salt-induced vacuole fission. Cells expressing Atg18WTHA3-yEGFP or Atg18T56E-HA3-yEGFP from centromeric  plasmids in a SEY6210 atg18∆, atg21∆ strain were logarithmically grown in SD-URA medium. They were stained  and imaged before and after the induction of vacuole fission   by a short salt shock Calcofluor white-stained  cell walls are only represented in the merge (blue). Scale bar: 5 µm. B, Quantification of the number of vacuoles per cell from A, n = 3 biological experiments with at least 100 cells per condition were scored; bars represent the mean and error bars the SEM. C, Epistasis of atg18T56E over a vps17∆ mutation. The indicated variants of Atg18-HA3-yEGFP  were expressed from plasmids in a SEY6210 atg18∆, atg21∆, vps17∆ strain. Cells were logarithmically grown in SD-URA  and imaged Scale bar: 5 µm. D, Quantification of the experiments from C, n = 3 independent experiments with at least 100 cells per condition scored; bars represent the mean and error bars the SEM .",
    "ncbi_link": "HA3: 
yEGFP: 
Atg18: 850577
atg18: 850577
atg21: 856004
vps17: 854300"
  },
  {
    "caption": "A  Colocalization of WIPI1  with Vps26A. The indicated  WIPI1mCherry variants and VPS26EGFP were expressed for 18 h in HK2  cells, from which endogenous WIPI1  had been deleted (WIPI1-KO). The cells were analyzed by confocal microscopy. Scale bars: 10 μm. Insets show enlargements of the outlined areas. B Colocalization  between WIPI1  variants and Vps26  was quantified in the cells from A using the Manders' colocalization  coefficient M2. The red line indicates the mean; n = 120 cells per condition, pooled from three independent experiments. P-values were calculated by t-test (analysis performed with 99% confidence ***p < 0.0001). C Expression  levels of WIPI1mCherry  variants. Lysates (50 μg of protein per sample) from the cells in A were analyzed by  SDS-PAGE  and Western blot  against WIPI1  and tubulin.",
    "ncbi_link": "EGFP: 
mCherry: 
VPS26: 9559
WIPI1: 55062"
  },
  {
    "caption": "D Depletion of VPS35. HK2  cells expressing the indicated WIPI1eGFP variants were transfected with siRNA against VPS35  (VPS35  KD) or a control siRNA pool. Lysates (50 μg per sample) from the cells were analyzed by  SDS-PAGE and Western blot  against Vps35   and tubulin. E Blots  from D were quantified on a LICOR Odyssey fluorescence imager. n=3. Red lines indicate the means, n = 3 independent experiments, using a Welch's t-test statistical analysis. Bars represent the mean and error bars the SD.",
    "ncbi_link": "eGFP: 
VPS35: 55737
WIPI1: 55062"
  },
  {
    "caption": "A, Tf  recycling. WIPI1-KO cells were transfected with WIPI1WT-eGFP, WIPI1S69E-eGFP  or  WIPI1S69A-eGFP for 18h. Then, they were serum-starved  for 1 h, loaded with  Alexa Fluor 568-conjugated Tf, chased at 37°C for 1 h without labeled Tf, and analyzed by  confocal microscopy. Scale bar: 10 μm. White dashed lines delineate the circumference of the cells. B, Quantification of Tf-fluorescence in the cells from a that expressed WIPI1  variants. Total cell fluorescence was integrated and corrected for background fluorescence. Mean values ± SD are shown. n = 3 independent experiments with a total of 150 cells analyzed per condition. P values were calculated by unpaired Student's t-test. 99% confidence: *** = p < 0.0001.",
    "ncbi_link": "eGFP: 
WIPI1: 55062"
  },
  {
    "caption": "ER Proliferation under UPR-Inducing Conditions(A) Determination of ER abundance in control and UPR-induced cells. Representative cells are shown. The UPR was induced in wild-type cells by addition of DTT. Ultrastructure of control cells and UPR-induced cells was analyzed using ImageJ. The lower images show traces of cortical ER (represented in magenta) and the nuclear envelope (NE, in blue). Vacuoles, nuclei, and mitochondria are indicated as V, N, and M, respectively.(B) Quantification of the ER proliferation during the UPR. UPR was induced and cells were collected for EM at the indicated time points. Length of the ER (as traced in [A]) was measured and divided by the area of the section. Data are plotted relative to time 0. Measurements for each time point correspond to the mean of 25 independent cell images.(C) Expression of HAC1i was induced by addition of 100 μM DOC for 3 h. ER was quantified as described above in (B).",
    "ncbi_link": "HAC1: 850513"
  },
  {
    "caption": "(A) Wild-type cells transformed with a plasmid containing GFP-Atg8 were grown for 4 h in synthetic media with no drug, with UPR-inducing conditions (+DTT and +TM), or under nitrogen starvation conditions (N starv), and then harvested for protein preparation. Protein extracts were analyzed by Western blotting using antibodies against GFP (top panel) or Hac1 (bottom panel). Total protein concentration was measured by BCA protein assay. Same concentration of protein was loaded in each lane, and transfer efficiency was checked by Ponceau staining. The identities of the different bands are indicated.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(B) Wild-type cells expressing GFP-Atg8 grown under the conditions described above were visualized by fluorescence microscopy.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "(C) GFP-Atg8 was detected in extracts from untreated hac1Δ cells or cells expressing HAC1i (+DOC) by Western blotting using antibodies against GFP.",
    "ncbi_link": "Atg8: 852200
hac1: 850513
HAC1: 850513"
  },
  {
    "caption": "(D) Western blot using antibodies against GFP of extracts from hac1Δ, ire1Δ, or vps4Δ pep4Δ cells expressing GFP-Atg8. Mutant cells were grown under regular conditions, UPR-inducing conditions (+DTT), or nitrogen starvation conditions (N starv).",
    "ncbi_link": "Atg8: 852200
hac1: 850513
ire1: 856478
pep4: 855949
vps4: 856303"
  },
  {
    "caption": "Localization of GFP-Atg8 during UPR InductionSome of the DTT-treated cells shown in Figure 4B expressing GFP-Atg8 and Sec61-cherry (as an ER marker) were visualized using fluorescence microscopy. GFP-Atg8 localizes in close proximity to the ERAs detected by the ER marker.",
    "ncbi_link": "Atg8: 852200"
  },
  {
    "caption": "Atg8 and Other ATG Genes Are Necessary during UPR InductionSerial dilutions for wild-type, hac1Δ, atg1Δ, atg8Δ, atg9Δ, atg16Δ, and atg20Δ deletion cells and vps4Δ pep4Δ double deletion cells were grown on rich-media plates with no drug (YPD) or with different concentrations of tunicamycin (TM; 0.2 or 1.0 μg/ml). atg19Δ gave an identical result to the other autophagy genes shown here (unpublished data).",
    "ncbi_link": "atg1: 852695
atg16: 855194
atg20: 851445
atg8: 852200
atg9: 851406
hac1: 850513
pep4: 855949
vps4: 856303"
  },
  {
    "caption": "(E) Genome browser images of ChIL-seq for H3K27ac and PolII-S5P and bulk tissue  RNA-seq data at the Alb locus in  liver tissues.",
    "ncbi_link": "Alb: 11657"
  },
  {
    "caption": "(B) The IGV tracks of H3K27ac ChIL-seq at identified tissue-specific enhancers of Rxra, Gnat3, Eps8, and a house-keeping gene of Actb  loci are shown with the replicates.",
    "ncbi_link": "Actb: 11461
Eps8: 13860
Gnat3: 242851
Rxra: 20181"
  },
  {
    "caption": "(F) Hnf4ɑ  binds to the SE at Alb  gene loci.",
    "ncbi_link": "Alb: 11657"
  },
  {
    "caption": "(E) The tissue-specific genes identified by PolII  S5P ChIL-seq. The IGV tracks of all replicates of  PolII S5P  ChIL-seq are shown at each specific gene (Trf, Myh6, and Meig for the liver,  heart, and testis, respectively). Actb is also shown as the ubiquitously expressed gene in the three tissues.",
    "ncbi_link": "Actb: 11461
Meig: 104362
Myh6: 17888
Trf: 22041"
  },
  {
    "caption": "(B) PolII  S5P  ChIL-seq signal of the marker genes of mature skeletal muscle (Acta1) and  macrophages (Cd68).",
    "ncbi_link": "Acta1: 11459
Cd68: 12514"
  },
  {
    "caption": "(C) Expression, TSS level, and TR of genes. EEF1A1  is shown as a control housekeeping gene. The horizontal dotted line indicates the median level of all genes. Error bars indicate 95% confidence intervals for each estimate indicated by dots (N=1 for each).",
    "ncbi_link": "EEF1A1: 13627"
  },
  {
    "caption": "(A) Quantification of cell death in 293 cells24 h after transfection with luciferase, p55/TNFR1, DRP-1 Δ73 or DAPk ΔCaM, and GFP. Graphs show the percentage of GFP-positive cells with altered cell morphology. (B) Photographs of GFP-positive cells cotransfected with luciferase (1), p55/TNFR1 (2), DRP-1 Δ73 (3), or DAPk ΔCaM (4).",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(C) Photographs showing the overlay of GFP and phase-contrast images of 293 cells24 h after transfection with GFP and luciferase (1) or with GFP- DAPk (2 and 3); both a blebbing GFP-DAPk-expressing cell (2, arrows indicate blebs) and spread nontransfected cells are shown (3).",
    "ncbi_link": "luciferase: 
DAPk: 23604"
  },
  {
    "caption": "(D) Hoechst staining (4-6) of GFP-positive 293 cells (1-3) 60 h after cotransfection with GFP and DAPk ΔCaM (1 and 4), DRP-1 Δ73 (2 and 5), or p55/TNFR1 (3 and 6). Arrows point to condensed nuclei resulting from DRP-1 Δ73 or DAPk ΔCaM transfections (4 and 5).",
    "ncbi_link": "DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(A) Scoring loss of mitochondrial membrane potential (ΔΨm). 293 cells expressing luciferase (black), DRP-1 Δ73 (pink), DAPk ΔCaM (purple), and Bax (green) were assayed for loss of mitochondrial membrane potential 24 h after transfection using flow cytometric analysis of TMRM fluorescence. The fraction of TMRM-negative cells calculated from three experiments is shown in the graph below. The small increase in TMRM fluorescence in the kinase-transfected cells is not statistically significant.",
    "ncbi_link": "luciferase: 
Bax: 581
DAPk: 23604
DRP-1: 10059"
  },
  {
    "caption": "(B) Scoring the release of cytochrome C from mitochondria. 293 cells cotransfected with luciferase (1 and 2), Bax (3 and 6), DRP-1 Δ73 (7 and 8), or DAPk ΔCaM (9 and 10) and GFP constructs were incubated for 24 h and immunostained using anti-cytochrome C antibodies. Cells were visualized for cytochrome C (left) or GFP (right) fluorescence. Bax-transfected spread (3 and 4) or blebbed (5 and 6) cells are shown. In fields that also contain nontransfected cells, arrows point to GFP-positive cytochrome C-stained cells.",
    "ncbi_link": "luciferase: 
Bax: 581
DAPk: 23604
DRP-1: 10059"
  },
  {
    "caption": "(C) Assessing the effects of Bcl-2 and Bcl-XL. 293 cells were cotransfected with luciferase, DRP-1 Δ73, DAPk ΔCaM, or Bax, and either Bcl-2 or Bcl-XL together with GFP. GFP-positive cells were visualized by fluorescent microscopy and scored for the appearance of cell death morphology 24 h after transfection. Total cell death refers to the sum of all morphological changes observed.",
    "ncbi_link": "luciferase: 
Bax: 581
Bcl-2: 596
Bcl-XL: 598
DAPk: 23604
DRP-1: 10059"
  },
  {
    "caption": "(A) Transmission electron micrographs of 293 cells transfected with luciferase (1) p55/TNFR1 (2a-2c), DRP-1 Δ73 (3a and 3b; part of fig. 3b is magnified on its right), and DAPk ΔCaM (4). The different stages of autophagic development are depicted as follows: immature autophagic vesicles (double arrow), mature autophagic vesicles and autolysosomes (black arrow), and residual bodies (dashed arrow). Empty vacuoles (white arrow) are also shown. Arrowheads show condensed and fragmented chromatin. m, mitochondria; g, Golgi apparatus. Bar, 1 μm.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(B) Transmission electron micrographs of MCF-7 cells transfected with luciferase (1), p55/TNFR1 (2a-2c), DRP-1 Δ73 (3a and 3b), and DAPk ΔCaM (4). Immature autophagic vesicles (double arrow), autophagic vesicles (black arrow), and residual bodies (dashed arrow) are shown. Insets in B, 2b and 2c, correspond to empty vacuoles, whereas those in B, 3a and 4, correspond to autophagic vesicles. Arrowheads show condensed and fragmented chromatin. m, mitochondria; dm, darkened mitochondria; n, nucleus; g, Golgi apparatus; v, vacuoles; ly, lysosomes; er, endoplasmic reticulum.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(A) Quantification of autophagy in 293 and MCF-7 cells. Graphs show the percentage of MDC-positive cells resulting from luciferase or DRP-1 Δ73 transfections (mean ± SD calculated from triplicates of 100 cells each; note that total cell number comprises transfected and nontransfected cells). These experiments were repeated three times with reproducible results.",
    "ncbi_link": "luciferase: 
DRP-1: 10059"
  },
  {
    "caption": "(B) Photographs of MDC-stained MCF-7 cells from the same experiment shown in A. Arrows point to MDC-positive cells. Transfections: luciferase (1a and 1b) and DRP-1 Δ73 (2a and 2b) at low (a) and high (b) magnifications.",
    "ncbi_link": "luciferase: 
DRP-1: 10059"
  },
  {
    "caption": "(A) Quantification of cell death-associated morphologies in 293 cells. Graphs show the percentage of cells harboring all spectrum of morphological changes occurring as a result of luciferase, p55/TNFR1, DRP-1 Δ73, or DAPk ΔCaM transfections in the presence or absence of the caspase inhibitors BD-fmk or z-VAD-fmk (100 μM; mean ± SD calculated from triplicates of 100 cells each). This experiment was repeated three times with reproducible results.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(C) Graphs show the percentage of cells harboring the complete spectrum of death-associated morphological changes occurring as a result of cotransfections of luciferase, p55/TNFR1, DRP-1 Δ73, or DAPk ΔCaM with the caspase inhibitor crmA or control luciferase vector (mean ± SD calculated from triplicates of 100 cells each). Immunoblot shows the expression levels of transfected HA-tagged DAPk and DRP-1 Δ73, confirming that cotransfection with crmA did not alter expression of the death-inducing proteins.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(D) Transmission electron micrographs of 293 cells transfected with p55/TNFR1 (1) or DRP-1 Δ73 (2a and 2b; parts of these figures are magnified at the right) and treated with the caspase inhibitor BD-fmk (100 μM). Immature autophagic vesicles (double arrow), autophagic vesicles (black arrow), and autolysosomes (white arrow) are shown. m, mitochondria; g, Golgi apparatus.",
    "ncbi_link": "DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(E) Western blots of cell lysates prepared from HeLa cells transfected with luciferase, p55/TNFR1, DRP-1 Δ73, or DAPk ΔCaM and GFP and incubated for 24 h. Blots were reacted with anti-PARP antibodies, anti-caspase-8 antibodies, anti-caspase-3 antibodies, anti-HA antibodies for DRP-1 Δ73 and DAPk ΔCaM detection, and anti-β-tubulin antibodies to quantitate protein loading.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(A) 293 cells were cotransfected with p55/TNFR1 in combination with DAPk death domain fused to GFP or DRP-1 K42A and pEGFP-N1 vector. A control luciferase vector was also used. GFP-positive cells were visualized by fluorescent microscopy and scored for the appearance of membrane blebbing 24 h after transfection.",
    "ncbi_link": "luciferase: 
DAPk: 23604
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(B) Photographs of the various categories of p55/TNFR1-transfected 293 cells: spread cells (1), blebbed cells (2), condensed cells (3), cells displaying a fragmented cytoplasm (4), and cells carrying fragmented nuclei within a noncondensed cytoplasm (5). (C) Quantification of each death morphology observed 24 h after transfection with GFP, p55/TNFR1, and either luciferase or DRP-1 K42A.",
    "ncbi_link": "luciferase: 
DRP-1: 10059
p55: 7132
TNFR1: 7132"
  },
  {
    "caption": "(A and B). Quantification of autophagy in MCF-7 cells. MCF-7 cells were transfected with luciferase or FLAG-DRP-1 K42A followed by steroid withdrawal (serum starvation plus 10−6 M tamoxifen treatment) (A) or by serum and amino acid starvation (B) (mean ± SD calculated from triplicates of 100 cells each). These experiments were repeated three times with reproducible results. Proteins extracted from the transfected cells were subjected to Western blot analysis with anti-FLAG and anti-β-tubulin antibodies.",
    "ncbi_link": "luciferase: 
DRP-1: 10059"
  },
  {
    "caption": "(C) Photographs of the MDC-stained steroid withdrawn MCF-7 cells taken from the same experiment shown in A. Transfections: luciferase (1a and 1b) and DRP-1 K42A (2a and 2b) at low (a) and high (b) magnifications.",
    "ncbi_link": "luciferase: 
DRP-1: 10059"
  },
  {
    "caption": "(E) DAPk antisense-transfected and control DHFR-transfected polyclonal populations of HeLa cells were incubated with hygromycin B (200 μg/ml) in the presence or absence of IFN-γ (1,000 U/ml) and BD-fmk (50 μM). Detection of autophagic vesicles was performed 2 d later using the MDC dye. Graphs represent mean ± SD of MDC-positive cells calculated from triplicates of 100 cells each.",
    "ncbi_link": "DAPk: 23604
DHFR: 1719"
  },
  {
    "caption": "DRP-1 is localized to the lumen of autophagic vesicles. Immunogold staining of 293 cells expressing HA-DRP-1 reveals a specific staining of DRP-1 in the lumen of double membrane autophagosomes containing cytoplasmic material (A and B) in autophagosomes containing organelles and vacuoles (C) and inside the body of autolysosomes containing digested matter (D). The gold particles do not overlap with the phagocytosed organelles in C or the lysosomes in D.",
    "ncbi_link": "DRP-1: 10059"
  },
  {
    "caption": "HeLa cells were transfected with specific RNAi oligonucleotides (siTFG) or unrelated oligonucleotides as a negative control (siCTR) and grown in fed or starved conditions for 1h. Cells were fixed and co-labelled with ULK1 (red) antibody and A) anti-CALNEXIN (CANX) (green) antibody to highlight ER structures; (n=3 independent experiments, n≥16 fields analysed) B) GOLGIN97 (green) antibody to label GOLGI complex; (n=3 independent experiments, n=12 fields analysed) C) SEC31A (green) to point out COPII vesicles. (n=3 independent experiments, n≥16 fields analysed)",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "F) HeLa cells were co-transfected with control siRNA and an empty vector (EV), or 3'UTR TFG siRNA together with an EV or HA-TFG plasmids. Cells grown for 1h in starvation medium then fixed, permeabilized, and labelled with anti-ULK1 (green) and anti-ERGIC53 (red) antibodies respectively. Hoechst was used to stain nuclei. Co-localization analysis were performed as in D). Values of Mander's coefficient for ULK1, expressed as percentage, are mean ± SEM. Statistical analyses were performed by one-way ANOVA followed by Dunnetts's multiple comparison test. *, P<0,05. (n=3) (n=3 independent experiments, n≥9 fields analysed). Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A) HeLa cells were transfected with specific RNAi oligonucleotides (siTFG) or unrelated oligonucleotides as a negative control (siCTR) and grown in fed (FED) or starvation conditions (STV) in the presence or absence of CLQ for 1h. Cells were then fixed and stained using LC3B-II (red) antibody. Analysis of LC3B puncta number is reported (bottom). All data are expressed as the mean value ± SEM. Statistical analysis were performed by two-way ANOVA followed by Tukey's multiple comparison test. ****, P<0.0001. (n=4 independent experiments, n≥25 fields analysed). Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "A) HeLa cells were transfected with specific RNAi oligonucleotides (siTFG) or unrelated oligonucleotides as a negative control (siCTR); after culturing cells in fed (FED) or starvation conditions (STV) for 1h, cells were fixed and labelled with the indicated antibodies. Co-localization analysis was performed by using ImageJ Jacop plugin and mean ± SEM of Mander's coefficients of ULK1, expressed as percentage, is reported (bottom). White arrowheads point at co-localization events between ULK1 and LC3B; white arrows track puncta not co-localizing; N, nucleus. Statistical analyses were performed by two-way ANOVA followed by Tukey's multiple comparison test. *, P<0,05; **, P<0.01; ****, P<0.0001. (n=3 independent experiments, n≥16 fields analysed). Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "HEK293 cells stably expressing either GFP-ATG13 (B) were transiently transfected with specific RNAi oligonucleotides (siTFG) or unrelated oligonucleotides as a negative control (siCTR), together with CFP-LC3B plasmid (visualized in red) and cultured in starved conditions for 40'. Wide-field live-cell imaging of starved cells were taken by cellSens microscope. Representative images of lifespan of ATG13 (B) are reported. Images of ATG13 (B) forming association with LC3B-II are also shown. The appearance of LC3B on ATG13 (B) (bottom right) (C) puncta were quantified and reported. All values are expressed in seconds (sec) as mean ± SEM. Yellow arrowheads point at the DFCP1 and LC3B particles in the first frame from their onset, white arrowheads and white arrows show omegasomes and autophagosomes as indicated. Statistical analyses were performed by unpaired Student's t‐test. *, P<0,05; **, P<0.01.(n=3 independent experiments, n=50 events/condition analysed). Scale bar 1 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "HEK293 cells stably expressing either GFP-DFCP1 (C) were transiently transfected with specific RNAi oligonucleotides (siTFG) or unrelated oligonucleotides as a negative control (siCTR), together with CFP-LC3B plasmid (visualized in red) and cultured in starved conditions for 40'. Wide-field live-cell imaging of starved cells were taken by cellSens microscope. Representative images of lifespan of both ATG13 (C) are reported. Images of DFCP1 (C) forming association with LC3B-II are also shown. The appearance of LC3B on on DFCP1 (bottom right) (C) puncta were quantified and reported. All values are expressed in seconds (sec) as mean ± SEM. Yellow arrowheads point at the DFCP1 and LC3B particles in the first frame from their onset, white arrowheads and white arrows show omegasomes and autophagosomes as indicated. Statistical analyses were performed by unpaired Student's t‐test. *, P<0,05; **, P<0.01.(n=3 independent experiments, n=50 events/condition analysed). Scale bar 1 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "E) HeLa cells stably expressing GFP-ATG13 and CFP-ATG16 were transiently co-transfected with DsRed-Rab7 and TFG siRNA (siTFG). Cells were cultured in starved conditions for 1h. Representative electron micrographs (x3900) and merge of the three fluorophores CLEM are shown. Micrographs at higher magnification (x13500) of a region showing the three fluorophores split and merged is reported. Scale bars: 5 μm upper panels, 1 μm bottom panels.",
    "ncbi_link": "DsRed: 
Rab7: 7879
TFG: 10342"
  },
  {
    "caption": "G) Control (TFG-WT) and patient's (TFG-R106C) fibroblasts were grown in fed or starvation conditions for 1h. Cells were fixed, permeabilized, and labelled with anti-ULK (red) antibody. Hoechst was used to stain nuclei. The average of ULK1 puncta number per cell is shown (bottom). All data are expressed as the mean value ± SEM. Statistical analysis was performed by two-way ANOVA followed by Tukey's multiple comparison test. *, P<0.05; ***, P<0,001; ****; P<0,0001. (n=3 independent experiments, n≥14 fields analysed). Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "HeLa cells stably expressing untagged TFGwtLIR or TFGmutLIR3 were transfected with 3'UTR TFG siRNA, starved for 1h, fixed, permeabilized and immunolabelled with ULK1 (red) Hoechst was used to stain nuclei. ULK1 puncta number (G) was analysed and reported as mean ± SEM in the graph (right) (n=3 independent experiments, n=24 fields analysed). Values of Mander's coefficient for ULK1, expressed as percentage, are reported as mean ± SEM (bottom graph). (n=3 independent experiments, n=19 fields analysed) White arrowheads point at co-localization events between ULK1 and ERGIC. Statistical analyses were performed by unpaired Student's t‐test. **, P<0,01; ***, 0,001. Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "HeLa cells stably expressing untagged TFGwtLIR or TFGmutLIR3 were transfected with 3'UTR TFG siRNA, starved for 1h, fixed, permeabilized and immunolabelled with ULK1 (red) alone or ULK1 (red) and ERGIC53 (green) (H). Hoechst was used to stain nuclei. analysed). Co-localization analyses (H) were performed by Jacop plugin. Values of Mander's coefficient for ULK1, expressed as percentage, are reported as mean ± SEM (bottom graph). (n=3 independent experiments, n=19 fields analysed) White arrowheads point at co-localization events between ULK1 and ERGIC. Statistical analyses were performed by unpaired Student's t‐test. **, P<0,01; ***, 0,001. Scale bar 5 μm.",
    "ncbi_link": "TFG: 10342"
  },
  {
    "caption": "M) HeLa cells stably expressing untagged TFGwtLIR or TFGmutLIR3 were co-transfected with HA-LC3C and Myc-ULK1 plasmids as indicated. Cells were starved for 30' and protein extracts were immunoprecipitated using an anti-HA antibody or IgG as negative control. Protein extracts were analysed by WB to detect ULK1, LC3C, TFG and ACTIN as indicated.",
    "ncbi_link": "HA: 
Myc: 
LC3C: 440738
TFG: 10342
ULK1: 8408"
  },
  {
    "caption": "D. Viability of HEK 293FT/CD31-GFP cells (transduced with CD31-GFP) as a percentage of untreated control cells after incubation with indicated concentrations of toxins (24 h, 37°C). Data (technical replicates) are represented as means (n = 4) ± SD.",
    "ncbi_link": "GFP: 
CD31: 18613"
  },
  {
    "caption": "B-E) Expression of Hep-ID (n=13 genes), Hep-IDCONNECT (n=26 genes) and remaining TF-encoding genes from cluster G (Others; n=82 genes) was monitored in indicated transcriptomic data Box plots show log2 fold changes between adult versus newborn mouse livers (B), MPH of Hnf4ahep-/- (Hnf4a KO) versus wild-type mice (C), a meta-analysis of severe mouse liver injuries versus control livers and microdissected hepatocytes from alcohol-related human liver cirrhosis (alcoholic steatohepatitis) versus control livers (E). Box plots are composed of a box from the 25th to the 75th percentile with the median as a line. Whiskers extent to the most extreme data point which is no more than 1.5 times the interquartile range from the box. Statistical significance was assessed using one-sided Wilcoxon rank sum test with Benjamini-Hochberg correction for multiple testing to determine if the mean log2 FC was statistically lower (B, D, E) or higher (C) than 0. *q<0.05.",
    "ncbi_link": "Hnf4a: 15378"
  },
  {
    "caption": "D) Average gene expression levels of Mlxipl in the livers of WT and XBP1hep-/- mice across circadian time (n=2 mice per group). Error bars show standard deviations.",
    "ncbi_link": "Mlxipl: 58805
XBP1: 22433"
  },
  {
    "caption": "mRNA expression of the indicated genes was monitored using RT-qPCR in HepG2 cells treated with T3 or GC-1 for 24h or 96h. For Hnf4a, the log2 fold change in the ratio of P1 over P2 promoter-derived isoforms is also shown. Gray dots show the results obtained from the 3 independent biological replicates (each performed in technical triplicates). One-sample t-test with Benjamini-Hochberg correction for multiple testing was used to determine if the mean log2 FC was statistically different from 0. *q<0.05.",
    "ncbi_link": "Hnf4a: 3172"
  },
  {
    "caption": "B-D) mRNA expression of the indicated genes was monitored in mouse livers using RT-qPCR. Mice treated with IL1B+T3 were subdivided into tertiles based on the mean expression of the Dio1 and Hectd3 genes and defined as low, intermediate or high T3 responsiveness groups (Low resp., Int. resp. and High resp., respectively). Fold change relative to the mean of the control group is shown using box plots composed of a box from the 25th to the 75th percentile with the median as a line (n=13 mice for the PBS group, 17 for the IL1B group and 10 for the other groups). Whiskers extend to the maximum and minimum values. Statistical differences between the High resp. and the other IL1B-treated groups were defined using Kruskal-Wallis with two-sided Wilcoxon pairwise comparison tests followed by Benjamini-Hochberg correction for multiple testing correction. *q<0.05.",
    "ncbi_link": "Dio1: 13370
Hectd3: 76608"
  },
  {
    "caption": "BHK cells were transfected with either human ACE2 or empty vector, subsequently infected with VSV-reporter particles pseudotyped with chimeric spikes, luciferase was measured and normalized to no pseudotype as a readout for cell entry. Shown are the data for 3 replicates.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Primate cells, were infected with VSV-particles pseudotyped with the lineage B chimeric spike panel. Pseudotypes were either left untreated or incubated with trypsin before addition to the cells. Luciferase was measured and normalized to particles produced without pseudotype. Shown are the data for 3 replicates.",
    "ncbi_link": "Luciferase: "
  },
  {
    "caption": "human cells were infected with VSV-particles pseudotyped with the lineage B chimeric spike panel. Pseudotypes were either left untreated or incubated with trypsin before addition to the cells. Luciferase was measured and normalized to particles produced without pseudotype. Shown are the data for 3 replicates.",
    "ncbi_link": "Luciferase: "
  },
  {
    "caption": "Pseudotypes were used to infect cells expressing hACE2, hDPP4, hAPN, or empty vector, without protease treatment.",
    "ncbi_link": "hACE2: 59272
hAPN: 290
hDPP4: 1803"
  },
  {
    "caption": "VSV pseudotypes were generated with the indicated RBD and used to infect BHKs transfected with either human ACE2 or empty vector. Shown are data for 3 replicates.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Pseudotypes with indicated spike constructs were left untreated or treated with trypsin and subsequently used to infect BHK cells transfected with human ACE2. Shown are data for 3 replicates.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(A) Unlabeled or Cy5-labeled dsRNA corresponding to the first 200 nucleotides of either the Renilla luciferase (dsRNA-RL) or the GFP (dsRNA-GFP) coding sequences visualised on gel stained with ethidium bromide (EtBr-stained, top) or by in-gel fluorescence (bottom).",
    "ncbi_link": "GFP: 
Renilla: "
  },
  {
    "caption": "(A) Mavs+/- and Mavs-/- MEFs stably expressing GFP were transfected or not (mock) with the indicated Cy5-labeled dsRNAs (top panels) or siRNAs (bottom panels). GFP level was measured in Cy5+ cells by flow cytometry 72 hours (hrs) post-transfection.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(B) Mavs+/- and Mavs-/- MEFs stably expressing d2GFP were transfected or not (mock) with the indicated Cy5-labeled dsRNAs. The level of d2GFP in Cy5+ cells was measured at various timepoints post-transfection as indicated. Histograms plots show d2GFP level 48 hrs post-transfection. Bar graphs show 3 timepoints as indicated.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(C) WT, Ifnar1+/- or Ifnar1-/- MEFs stably expressing d2GFP were transfected or not (mock) with the indicated Cy5-labeled dsRNAs and d2GFP level in Cy5+cells was monitored by flow cytometry at 48 hrs post-transfection.",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "(A) Mavs+/- and Mavs-/-MEFs stably expressing GFP were incubated with either a neutralising antibody against IFNAR (α-IFNAR Ab), an isotype control antibody (IgG1) or no antibody (no Ab). Cells were then were transfected or not (mock) with Cy5-labeled dsRNA as indicated and GFP level monitored in Cy5+cells 72 hrs post-transfection.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(B) Mavs-/-MEFs stably expressing d2GFP were treated with recombinant IFN (200 U/ml) for 24 hrs prior to transfection or not (mock) with Cy5-labeled dsRNA, as indicated. IFN treatment was maintained for 2 days post-transfection and then GFP level monitored in Cy5+cells.",
    "ncbi_link": "Mavs: 228607"
  },
  {
    "caption": "(A) Northern blot analysis of Ifnar1-/- MEFs at 24 h.p.t with the indicated dsRNA or transfection reagent alone (mock) using a probe specific for dsRNA-GFP (top) or dsRNA-RL (bottom). Reactions from a dicing assay using the indicated dsRNA incubated in vitro with immunoprecipitated FLAG-human Dicer were loaded in parallel. Two lanes (delimited by dashed lines) were left empty between the Ifnar1-/- MEFs transfected samples and the in vitro dicing assay reactions. A miRNA marker containing 3 synthetic ssRNA oligonucleotides of 17, 21 and 25-nt in length was run in parallel. Endogenous U6 was used as a loading control. Signals corresponding to the dsRNA-derived siRNAs are indicated with an arrow. The membrane was first probed for dsRNA-GFP (top), then probed for the miRNA marker (top left) and subsequently stripped and reprobed for dsRNA-RL (middle) and finally stripped and reprobed for both U6 (bottom) and for the miRNA marker again (middle left).",
    "ncbi_link": "GFP: 
U6: 
Ifnar1: 15975"
  },
  {
    "caption": "(B) Western blot of Dicer in d2GFP-expressing Mavs-/- MEFs either not transduced (NT) or transduced to express a non-targeting shRNA control (CTL shRNA) or two different Dicer-specific targeting shRNAs (DICER shRNA 1 and 2). P97 served as loading control.",
    "ncbi_link": "DICER: 192119
Mavs: 228607"
  },
  {
    "caption": "(D) Western blots of Ago2 in parental Mavs-/- MEFs stably expressing d2GFP and three Mavs-/- Ago2-/- clones generated by CRISPR/CAS9-mediated genome engineering. P97 served as loading control.",
    "ncbi_link": "Ago2: 239528
Mavs: 228607"
  },
  {
    "caption": "(E) Mavs-/- (parental line) and Mavs-/- Ago2-/- MEFs (clone 5.1) stably expressing d2GFP were transfected or not (mock) with the indicated Cy5-labeled dsRNAs and d2GFP level in Cy5+cells was monitored by flow cytometry 48 hrs later.",
    "ncbi_link": "Ago2: 239528
Mavs: 228607"
  },
  {
    "caption": "(A) Western blots for Ago2 (top) and HA tag (bottom) of parental Mavs-/- MEFs and two Mavs-/- Ago2-/- clones (clone 5.2 and 5.3; see Fig 4A) stably expressing d2GFP and transduced with an empty vector or a vector encoding HA-tagged wild-type (HA-mAgo2 WT) or catalytic mutant (HA-mAgo2 D597A) versions of mouse Ago2. β-actin served as loading control. The membrane was first analysed for Ago2 and β-actin, stripped and then analysed for HA tag.",
    "ncbi_link": "Ago2: 239528
Mavs: 228607"
  },
  {
    "caption": "(B) Parental non-transduced (NT) Mavs-/- MEFs and complemented Mavs-/- Ago2-/- MEFs as described in (A) were transfected or not (mock) with the indicated Cy5-labeled dsRNAs and d2GFP level in Cy5+cells was monitored by flow cytometry 48 hrs later.",
    "ncbi_link": "Ago2: 239528
Mavs: 228607"
  },
  {
    "caption": "(A) Ifnar1-/- MEFs were transfected with the indicated Cy5-labeled dsRNA and the next day were infected with SFV-Rluc at the indicated multiplicities of infection (MOI). Renilla luciferase activity was measured 24 hours later. Each bar represents mean + SD of biological duplicates and numbers above each pair of bars depict the fold-reduction in viral activity achieved with dsRNA-RL vs. dsRNA-GFP treatment.",
    "ncbi_link": "GFP: 
Renilla: 
Ifnar1: 15975"
  },
  {
    "caption": "(C) As in (a) but with Ifnar1-/- or Mavs-/- MEFs and a single dose of SFV-Rluc (MOI=0.1).",
    "ncbi_link": "Ifnar1: 15975
Mavs: 228607"
  },
  {
    "caption": "(D) As in (a) but with two Mavs-/- Ago2-/- clones (clone 5.2 and 5.3) individually complemented to express wild-type (HA-mAgo2 WT) or a catalytic mutant (HA-mAgo2 D597A) version of mAgo2 or transduced with a control vector (as described in Fig 5). SFV-Rluc was used at an MOI=0.1.",
    "ncbi_link": "Ago2: 239528
Mavs: 228607"
  },
  {
    "caption": "B Representative TIRF-M of DCP1-GFP (DCP1pro:DCP1-GFP transgene) in the lateral PM of epidermal cells showing the transient attachment of DCP1-positive puncta to the PM. Yellow arrowheads denote a PB that shows motility at the PM focal plane; blue arrowheads show a PB that transiently localizes to the PM. Scale bars: 2 μm. The corresponding kymographs are shown to the right. Right: distribution of immobile and mobile DCP1 molecules relative to the motility log(D) value of -0.75 (threshold; see Material and methods for details), in NS or HS conditions (D, diffusion coefficient). Inset: individual trajectories of mobile DCP1-GFP in NS and HS conditions (500 frames, n = 120), showing a combination of directional and Brownian motion for both NS/HS. The green arrowheads denote the beginning of the NS and HS tracks for DCP1-GFP.",
    "ncbi_link": "GFP: 
DCP1: 837357"
  },
  {
    "caption": "C Representative confocal micrographs from lines co-expressing RPS5apro:HF-mScarlet-DCP1 and PIN2pro:PIN2-GFP (epidermal cells, region 3, Scale bars: 5 μm). Bottom: polarity index of DCP1 in root meristematic cells (compared to propidium iodide (PI) and tubulin staining of root cells; N, biological replicates = 3 roots, n = 13 cells). Polarity index calculated as the ratio of average of apical and basal VS lateral side of fluorescence signal intensity of the root epidemies cells. The arrowhead in PIN2 indicates the cell plate or PM in DCP1. Right: representative confocal micrographs showing that PM localization is independent of the promoter used (DCP1pro, 35Spro; region 2, epidermal cells, or RPS5apro on the lower right). The details from the inset show increased localization at the cell edge (discussed later). mSc, mScarlet.",
    "ncbi_link": "GFP: 
HF: 
mSc: 
mScarlet: 
PIN2: 
DCP1: 837357
RPS5a: 820367"
  },
  {
    "caption": "B Representative confocal micrograph of DCP1-GFP (DCP1pro:DCP1-GFP, transgene) in root meristematic cells under NS/HS conditions (region 2). Scale bars, 5 μm. Note the depletion of DCP1 from the PM upon HS, but the increased edge/vertex signal (yellow arrowheads denote the vertex signal). Right: DCP1 signal intensity at the PM or edge/vertex (N, biological replicates = 3, n (pooled data of 3 biological replicates) = 18-23 PMs or edges/vertices).",
    "ncbi_link": "GFP: 
DCP1: 837357"
  },
  {
    "caption": "Confocal micrographs showing single optical sections PLA-assays producing signal that resembles spots. The antibodies used were anti-FLAG/anti-GFP detecting the HF-mScarlet-DCP1/ DCP2-YFP, respectively (RPS5apro:HF-mScarlet-DCP1 and 35Spro:DCP2-YFP). Inset 1: magnification showing the colocalization of PLA spots with DCP1 or DCP2 signals (colocalization and Pearson's correlation coefficient PCC value for the spots shown). The dotted white line in the PLA channel corresponds to the PM plane. Inset 2: positive PLA signal for DCP1 and DCP2 in the nucleus. \"n1-n3\" correspond to nuclei regions (green circles). On the right, note the PLA spot nearby the nucleus (\"detail of PLA signal\"). The chart shows the quantification of PLA spots per cell at puncta (cytoplasm) or on the PM (N, biological replicates = 3, n (pooled data of 3 biological replicates) = 16-33 cells). As a cautionary technical note, the cytoplasmic, nuclear or PM \"spots\" do not connote physiologically relevant puncta, condensates or PM clusters. Scale bar: 20 μm / 10 μm for the insets.",
    "ncbi_link": "35S: 
HF: 
mScarlet: 
YFP: 
DCP1: 837357
DCP2: 831201
RPS5a: 820367"
  },
  {
    "caption": "D Representative confocal micrographs showing DCP1 localization detected by α-DCP1 in the wild type (WT) or the scar1 scar2 scar3 scar4 (scar1234) quadruple mutant or in live-cell imaging of mScarlet-DCP1 (RPS5apro:HF-mScarlet-DCP1) in WT or brk1 mutant (bottom right; epidermal cells, region 3 for α-DCP1 and 2 for live-cell imaging). The arrowheads denote the lack of robust DCP1 localization in scar1234 at the edge/vertex. Small panels (insets) at right show details corresponding to the regions delineated by dashed lines, where arrowhead denotes the edge signal of DCP1 in WT; scale bars, 1 μm. Bottom: percentage of cells with proper edge/vertex localization and quantification of PB numbers (DCP1-foci; N, biological replicates = 3, n (pooled data of 3 biological replicates) = 18-35 cells).",
    "ncbi_link": "HF: 
mScarlet: 
scar1 : 817976
scar1: 817976
brk1: 816795
DCP1: 837357
RPS5a: 820367
scar2: 818425
scar4: 831687
scar3: 839791"
  },
  {
    "caption": "A Representative confocal micrographs showing colocalization between DCP1 or two DCP1 phosphovariants with LifeAct-mCherry in lines co-expressing DCP1pro:DCP1-GFP (or variants) and UBQ10pro:LifeAct-mCherry (cell edges are indicated by yellow arrowheads). Right: relative signal intensity of actin at cell edges/vertices (normalized to the PM) in epidermal cells (N, biological replicates = 3, n = 15-30, regions 2-3).",
    "ncbi_link": "GFP: 
LifeAct-mCherry: 
DCP1: 837357
UBQ10: 825880"
  },
  {
    "caption": "B Representative confocal micrographs showing actin localization in WT, dcp1-1, dcp1-3, scar1234, dcp2-1, dcp5 and pat1 upon phalloidin staining and graph (right) indicating the percentage of cells in region 3 with an accumulation of actin at edges in various genotypes (N, biological replicates = 3, n = 7-9 roots, bars show means + s.d.).",
    "ncbi_link": "scar1: 817976
dcp1: 837357
dcp2: 831201
 dcp5: 839152
pat1: 834867"
  },
  {
    "caption": "A SE-FRET efficiency between DCP1-GFP or its phosphovariants with SCAR2-mCherry (among the three different root regions; mainly epidermal cells). Scale bar: 50 μm. The arrowhead denotes high FRET efficiency at edges/vertices of region 3. Right: signal quantification of SE-FRET efficiency between the indicated combinations at the epidermis of 3 regions (N, biological replicates = 6, n (pooled data of 3 biological replicates) = 10).",
    "ncbi_link": "GFP: 
mCherry: 
SCAR2: 
DCP1: 837357"
  },
  {
    "caption": "C Representative confocal micrographs showing SCAR2-mCherry localization in WT and dcp1-3 mutant, respectively (root region 2, epidermal cells) and quantification of edge/vertex with SCAR2 a confined signal (N, biological replicates = 3, n = 5-8 cells).",
    "ncbi_link": "dcp1: 837357"
  },
  {
    "caption": "D Representative confocal micrographs showing the colocalization between DCP1-GFP or phosphovariants and SCAR2-mCherry in root meristematic cells (root region 2, epidermal cells). Scale bars: 10 μm. The insets show details of colocalization; the white arrowhead denotes the expansion of the SCAR2/DCP1 domain, while the yellow arrowheads the restricted edge/vertex SCAR2/DCP1 domains. Scale bars: 3 μm. The graph indicates the relative signal intensity for the indicated combinations (as Pearson's correlation coefficient; N, biological replicates = 3, n = 5 at edges/vertices: spread edges were not considered in calculations).",
    "ncbi_link": "GFP: 
DCP1: 837357"
  },
  {
    "caption": "A Representative images showing the phenotypes of dcp1 mutants and mutants in other PB core components or SCAR-WAVE components (5-day-old seedlings). The arrowheads show the growth defects of homozygous dcp1-1 or dcp2-1 mutants (denoted -/-; heterozygous denoted dcp1-1/DCP1; details are also shown). Lower: graph showing relative root length (N, biological replicates = 3, n (pooled data of 3 biological replicates) = 3-4 roots, bars show means + s.d).",
    "ncbi_link": "dcp1: 837357
DCP1: 837357
dcp2: 831201
SCAR: 831687///839791///817976///818425
WAVE: 831687///839791///817976///818425"
  },
  {
    "caption": "B DCP1 regulates cell expansion anisotropy. Representative confocal micrographs showing FM4-64 staining of the WT, dcp1-1 and dcp2-1 mutants (2 μM, 10 min). Scale bars, 20 μm. Right: percentage of isotropic cells per root meristem (%, epidermal cells) in each genotype (N, biological replicates = 3, n (pooled data of 3 biological replicates) = 3-5 roots, bars show means ± s.d). Examples of isotropic or anisotropic cells are shown, along with the developmental axis offset at the x- and y-axes.",
    "ncbi_link": "DCP1: 837357
dcp1: 837357
dcp2: 831201"
  },
  {
    "caption": "B Representative images of immunostainings  for OCLN, CDH1, ZO-1 and CLDN1  in choroid plexus of sodium propionate or sodium butyrate-treated AppNL-G-F mice. Scale bar: 50 μm. C-E Quantification of continuous length (C), maximal length (D), and expressed area (E) of theTJ immunostainings  displayed in (B) (n=5-6, biological replicates). Data information: Bars represent mean ± SEM. Statistics were performed with one-way ANOVA Bonferroni's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "App: 11820"
  },
  {
    "caption": "I Representative images of 6E10 staining  in brain  of sodium propionate or  sodium butyrate-treated AppNL-G-F mice. Scale bar: 1 mm. J Quantification of Aβ  plaque area and number in whole sagittal section of the brain  (n=3 mice; one section per mouse). Data information: Bars represent mean ± SEM. Statistics were performed with one-way ANOVA Bonferroni's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "App: 11820"
  },
  {
    "caption": "(A) Rates of protein degradation in skin fibroblasts from wild‐type (control) or PPCA(−/−) mice maintained in the presence (serum +) or absence of serum (serum −). Values are expressed as the percentage of initially radiolabeled proteins remaining at each time and are means ± SE of four different experiments.",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(B) Degradation of [14C]GAPDH after 30 min incubation with lysosomes isolated from wild‐type and PPCA(−/−) mice skin fibroblasts supplemented or deprived of serum was measured as described in Material and methods. Where indicated, 25 μg of RNase A were added. Values are means ± SE of four different experiments. Differences from the control value were significant to P 0.001 (**).",
    "ncbi_link": "PPCA: 19025
RNase A: 19752"
  },
  {
    "caption": "(C) Immunofluorescent staining for lamp2a and lamp1 of skin fibroblasts from wild‐type and PPCA(−/−) mice. Gain for lamp2a images (top) was 1/8 of the one for lamp1 (bottom) to visualize the punctate pattern of lamp2a in PPCA(−/−) mice. Inset: detail of the vesicular distribution of lamp2a. The gain in wild type was eight times the gain in PPCA(−/−) mice). Bars: 100 μm (top), 50 μm (bottom), 10 μm (inset).",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(D) Immunoblot analysis for lamp2a, all lamp2s, lamp1 or cathepsin D (cath D) of homogenates (75 μg of protein), lysosomes (10 μg of protein) and lysosomal membranes (L.MB) and matrices (L.MTX) (5 μg of protein) isolated from wild‐type (WT) and PPCA(−/−) skin fibroblasts. The bottom chart shows the densitometric quantification of the membrane proteins (means + SE) from four immunoblots similar to those shown here. Differences from the control value were significant to P 0.001 (**) and P 0.05 (*).",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(A) Immunoblot analysis for lamp2a, all lamp2s, lamp1, transferrin receptor (TFR) or cathepsin D (cath D) of liver homogenates (100 μg of protein) from wild‐type (WT), PPCA(−/−) and β‐galactosidase(−/−) (GM) mice. Right: densitometric quantification of three immunoblots (means + SE) similar to the ones shown here. Differences from the control value were significant to P 0.001 (**) and P 0.05 (*).",
    "ncbi_link": "β‐galactosidase: 
PPCA: 19025"
  },
  {
    "caption": "(A) Autofluorography of the sequential immunoprecipitation of lamp2a first (left) and all the remaining isoforms of lamp2 second (right) from metabolically labeled wild‐type and PPCA(−/−) mouse skin fibroblasts. Values are means ± SE of three different experiments similar to the ones shown in the upper panels.",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(B) Immunoblot analysis for lamp2a (top) and all lamp2 isoforms (bottom) in lysosomalmembranes from wild‐type (WT) or PPCA(−/−) mouseskinfibroblasts at different times after incubation at 37°C. The open arrowhead indicates the truncated form of lamp2 lacking the cytosolic/transmembrane region ( Cuervo and Dice, 2000b). Right shows the densitometric quantification (mean ± SE) of four different experiments similar to the one shown here. Values are expressed as percentage of remaining lamp2a, and are means ± 1 SE of three different experiments.",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(B) Immunoblot analysis for lamp2a at time 0 or after 40 min incubation at 37°C of lysosomes isolated from PPCA(−/−) cells (None) and PPCA(−/−) cells supplemented as in (A). At 40 min immunoblot with the antibody against the luminal region of lamp2a is depicted to show the truncated form of lamp2a (open arrowhead). Right: densitometric quantification for lamp2a (means + range of values) of two different experiments similar to the one shown. Values are expressed as percentage of the lamp2a present in non‐supplemented cells.",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(C) Immunoblot analysis for lamp2a at time 0 or after 40 min incubation at 37°C of lysosomes isolated from PPCA(−/−) cells (None) and PPCA(−/−) cells supplemented as in (A). At 40 min immunoblot with the antibody against the luminal region of lamp2a is depicted to show the truncated form of lamp2a (open arrowhead). Right: densitometric quantification for lamp2a (means + range of values) of two different experiments similar to the one shown. Values are expressed as percentage of the lamp2a present in non‐supplemented cells.",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(D) Immunocytochemistry for lamp2a of liver (top) and kidney (bottom) sections of age‐matched wild‐type (WT), PPCA(−/−) and bone marrow transplanted (BMT) mice. Bar, 50 μm (liver) or 100 μm (kidney).",
    "ncbi_link": "PPCA: 19025"
  },
  {
    "caption": "(A) Genome-wide ubiquitin binding profiles identify numerous regions of H2B-ubiquitylation in WT cells and distinct sites of non-H2B ubiquitylation ('ubiquitin-hotspot', ub-hotspot, ub-HS) which persist in h2b-K123R and rad6∆ strains, and increase in cdc48 mutants (cdc48-6). A 90 kb stretch of chromosome XIII (ChrXIII) is depicted. Chromatin immunoprecipitation was performed using the FK2 ubiquitin antibody (see also Appendix Fig. S1A) and enriched DNA was analyzed on NimbleGen arrays (Chip-chip). DNA from non-specific IgG-ChIP experiments served as background control. Significantly enriched regions are marked by bars above the respective ChIP-chip tracks and are summarized in Dataset EV1. Data represent means from two independent replicates, except for ubiquitin (FK2) in rad6∆ and IgG-ChIP in WT (n = 1). All experiments, including those using cdc48-6 and other temperature-sensitive (ts) alleles, were performed at 30°C (semipermissive temperature for ts-alleles) unless stated otherwise.",
    "ncbi_link": "cdc48: 851431
h2b: 851810
rad6: 852822"
  },
  {
    "caption": "(B) Seven ub-HSs show strong correlation between ubiquitin binding and Slx8 enrichment (Slx8-9myc ChIP). 16-kb-windows of the indicated regions centered around the ub-HSs are depicted for ubiquitin and Slx8 binding profiles. Ubiquitin (FK2) data for WT and cdc48-6 are from the same experiment as depicted in (A). Data represent means from two independent replicates.",
    "ncbi_link": "cdc48: 851431"
  },
  {
    "caption": "(D) Slx8 and Slx5 are recruited to ub-HSs. DNA from Slx8-9myc (top) or 3HA-Slx5 (bottom) ChIP experiments of the indicated strains was analyzed by quantitative real-time PCR (ChIP-qPCR) at selected ub-HSs. Data represent mean ± standard deviation (SD, n = 2). Consistent with a previous study, we did not observe any Slx8 enrichment at centromeres (van de Pasch et al, 2013), however, we note that we could not confirm the reported centromere binding of Slx5 (see also Appendix Fig. S2E).",
    "ncbi_link": "HA: 
myc: 
Slx5: 851549
Slx8: 856852"
  },
  {
    "caption": "(E) K48-linked ubiquitin chains accumulate in a cdc48 mutant (cdc48-3). Ub-K48 ChIP followed by qPCR for same loci as in (D) are depicted. See also Fig. EV1C-D. Data represent means ± SD (n = 2).",
    "ncbi_link": "cdc48: 851431"
  },
  {
    "caption": "(F) Slx5 and Slx8 are required for ub-HS formation. Ub-K48 ChIP-qPCR in strains lacking one subunit of the Slx5/Slx8 complex (slx5∆, slx8∆). Data represent means ± SD (n = 3).",
    "ncbi_link": "Slx5: 851549
slx5: 851549
Slx8: 856852
slx8: 856852"
  },
  {
    "caption": "(G) Ufd1 and Npl4 act in concert with Cdc48 to remove ubiquitylated proteins from ub-HS sites. Ub-K48 ChIP for the indicated strains grown at the semi-permissive temperature of 30°C. Data represent means ± SD (n = 2).",
    "ncbi_link": "Cdc48: 851431
Npl4: 852468
Ufd1: 852939"
  },
  {
    "caption": "B) A 39 bp fragment of ub-HS4 is sufficient to drive ectopic ub-HS formation. Fragments of ub-HS4 were integrated ectopically and ub-K48 ChIP-qPCR was performed for the endogenous ub-HS5 and the ectopic ub-HS4 fragments as depicted in (A). contr.: control, empty YI128-vector was integrated at LEU2. Experiments were performed in cdc48‑6 background. Data represent means ± SD (n = 2). Experimental mapping and bioinformatic prediction identify a similar ub-HS-motif. Comparison between the experimentally mapped ub-HS4 F7 (B) and the consensus motif of all ub-HSs identified by the MEME software.",
    "ncbi_link": "cdc48: 851431
LEU2: 850342"
  },
  {
    "caption": "E) Euc1 binds to the ub-HS-motif in a Y1H assay. Gal4-AD- or Gal4-AD-Euc1-encoding plasmids were transformed into a Y1H reporter strain as described in (D). Serial dilutions were spotted on control plates and plates lacking histidine with 20mM 3-amino-triazole (3AT). Cells were grown at 30°C for 3 days.",
    "ncbi_link": "Gal4: 855828
Euc1: 855138"
  },
  {
    "caption": "F) Euc1 is required for formation of ub-HSs. ChIP with ub-K48 specific antibodies was performed for the indicated strains and enriched DNA was analyzed by qPCR. Data represent means ± SD (n = 4).",
    "ncbi_link": "Euc1: 855138"
  },
  {
    "caption": "Euc1 binds to endogenous ub-HSs. Genome-wide binding profiles of K48-linked ubiquitin chains were obtained in ChIP-chip experiments as described in Fig. 1A. Euc1-ChIP experiments were performed with a polyclonal antibody raised against Euc1 aa 292-462. Data represent means from two independent replicates.",
    "ncbi_link": "Euc1: 855138"
  },
  {
    "caption": "Euc1 binds  to endogenous ub-HSs. Genome-wide binding profiles of Euc1  were obtained in ChIP-chip experiments as described in Fig. 1A. Euc1-ChIP experiments were performed with a polyclonal antibody raised against Euc1  aa 292-462. Data represent means from two independent replicates.",
    "ncbi_link": "Euc1: 855138"
  },
  {
    "caption": "(C) Euc1 can induce transactivation via its N-terminal 30 amino acids. Euc1 constructs under the endogenous EUC1 promoter were transformed in a reporter strain as described for Fig. 2D and serial dilutions were spotted on control or selective media to test HIS3-activation. Cells were grown at 30°C for 3 days.",
    "ncbi_link": "HIS3: 854377
EUC1: 855138
Euc1: 855138"
  },
  {
    "caption": "(D) Quantification of HIS3 mRNA levels from strains used in (C). Cells were grown in liquid media with selection for the transformed plasmids (SC-Leu), harvested in logarithmic growth phase and total mRNA was prepared. After reverse transcription, HIS3 mRNA levels were quantified using qPCR (RT-qPCR), normalized first to ACT1 mRNA and then to the empty vector control strain. Data represent means ± SD (n = 4). p = 2.43*10-5 (Student's t-test).",
    "ncbi_link": "ACT1: 850504
HIS3: 854377"
  },
  {
    "caption": "(A) Euc1 interacts with SUMO pathway proteins in a yeast two-hybrid (Y2H) assay. A Y2H reporter strain (PJ69-7a) was transformed with Gal4 DNA-binding domain (BD) and Gal4 activation domain (AD) fusion constructs in the indicated combinations. AD-SUMO-GG can be conjugated to SUMOylation substrates, while AD-SUMO-AA is conjugation-deficient. Cells were spotted on control media or selective media (- His) and grown for 3 and 6 days, respectively.",
    "ncbi_link": "Gal4: 855828
SUMO: 852122"
  },
  {
    "caption": "(B) Euc1 is SUMOylated by Ubc9, Siz1 and Siz2 on K231. Euc1 was immunoprecipitated from the indicated strains and eluates were probed by WB against SUMO (top) and Euc1 (bottom). An up-shifted band corresponding to Euc1SUMO was detected with both antibodies. Asterisks denote non-specific bands.",
    "ncbi_link": "Siz2: 854327
Siz1: 852018
Ubc9: 851495
Euc1: 855138"
  },
  {
    "caption": "(C) Euc1 is predominantly monoSUMOylated on lysine 231. Denaturing NiNTA-pulldowns (NiNTA-PD) with strains expressing His-tagged SUMO (HisSUMO) as indicated and 3FLAGEuc1 constructs under the control of an ADH promoter. Covalently SUMO-modified proteins were enriched and eluates probed with a FLAG antibody to visualize SUMOylated Euc1. Eluates were probed for SUMO to control for equal pull-down, Pgk1 was probed as input control. Euc1-KR denotes the K231R mutation here and hereafter.",
    "ncbi_link": "FLAG: 
His: 
ADH: 854068
SUMO: 852122
Euc1: 855138"
  },
  {
    "caption": "(D) Euc1 SUMOylation is required for ub-HS formation. Ub-K48 ChIP quantified by qPCR for the indicated strains. The ubx5∆ background was used to enhance the ubiquitin signal, similar results were obtained in a WT background. Data represent means ± SD (n = 3).",
    "ncbi_link": "ubx5: 851930
Euc1: 855138"
  },
  {
    "caption": "(E) Euc1 ubiquitylation depends on Slx8 and partly on Euc1 SUMOylation. Denaturing NiNTA-PDs as described for (C) but with strains expressing His-ubiquitin (HisUbi) and 3FLAGEuc1 under the control of the ADH promoter. WBs were developed with a FLAG antibody to probe for 3FLAGEuc1, a ubiquitin blot served as PD-control and Dpm1 as input control. The slx8-CD allele carries the C206S, C209S-mutations (Xie et al, 2007).",
    "ncbi_link": "FLAG: 
His: 
ADH: 854068
Slx8: 856852
slx8: 856852
Ubi: 850620
ubiquitin: 850620
Euc1: 855138"
  },
  {
    "caption": "SUMOylated Euc1 is required to recruit Slx5 and Slx8 to ub-HSs. ChIP against Slx5 in the indicated genetic backgrounds were quantified by qPCR. Note that Slx5 is still recruited  in the absence of Slx8 (3HA-Slx5 slx8∆), but not vice versa (Slx8-9myc slx5∆). Data for WT and 3HA-Slx5 in (F) and WT",
    "ncbi_link": "HA: 
myc: 
Slx5: 851549
slx5: 851549
Slx8: 856852
slx8: 856852
Euc1: 855138"
  },
  {
    "caption": "SUMOylated Euc1 is required to recruit Slx8 to ub-HSs. ChIP against Slx8 in the indicated genetic backgrounds were quantified by qPCR. Note that Slx5 is still recruited in the absence of Slx8 (3HA-Slx5 slx8∆), but not vice versa (Slx8-9myc slx5∆). Data for WT and Slx8-9myc in (G)",
    "ncbi_link": "HA: 
myc: 
Slx5: 851549
slx5: 851549
Slx8: 856852
slx8: 856852
Euc1: 855138"
  },
  {
    "caption": "(A) Euc181-183 binds to Slx5 in Y2H assays. Y2H assay performed as in Fig. 4A. Serial dilutions were spotted for each plasmid combination and cells were grown at 30°C for 2 days. The Slx5-RING∆ construct is deleted for the Slx5 C-terminus from beginning of the RING-domain (∆aa 488-619). See also Fig. EV3B.",
    "ncbi_link": "Slx5: 851549"
  },
  {
    "caption": "(C) Euc1 binds  to Slx5 in vivo. Cell lysates from an euc1∆ strain expressing the indicated 3FLAGEuc1 constructs from plasmids (under EUC1 promoter) were subjected to immunoprecipitation using anti-FLAG beads. IP-eluates were probed by WB  with Slx5, SUMO  and Euc1  antibodies, inputs were probed with Slx5, FLAG  and Dpm1  antibodies (top to bottom). Note that the Euc1-Slx5 interaction  is independent of the Slx8  ligase activity (slx8-CD, lanes 5-8).",
    "ncbi_link": "FLAG: 
Slx8: 856852
slx8: 856852
EUC1: 855138
euc1: 855138
Euc1: 855138"
  },
  {
    "caption": "(D) Euc1 Slx5-binding mutants (SBM1, SBM2) affect Euc1-Slx5 interaction in Y2H assays. AD-Euc181-183 constructs harboring mutations in the region required for Slx5 binding were probed for interaction with BD-Slx5 constructs as described in Fig. 4A. Mutations: SBM1: aa 139-143 ENQKK>ANAAA, SBM2: aa 162-165 KEVF>AAAA. Serial dilutions were spotted and cells were grown at 30°C for 2 days. See Appendix Fig. S6A for expression levels.",
    "ncbi_link": "Slx5: 851549
Euc1: 855138"
  },
  {
    "caption": "(E) Euc1-SBM constructs show defective Slx5 binding in vivo. Mutations described in (D) were introduced into full-length Euc1 constructs (with or without the K231R mutation) and FLAG IPs were performed as described in (C). WB analysis showed strong Slx5-binding defects for the SBM1/SBM2 and SBM1+2 constructs (top panel, immunoprecipitated Slx5). WBs were probed as in (C).",
    "ncbi_link": "Euc1: 855138"
  },
  {
    "caption": "(F) The Slx5 middle domain (Slx5-Md) is required for interaction with Euc1. Y2H assays with AD-Euc181-183 and BD-Slx5 constructs. Slx5-Md: aa 201-335, Slx5-Md∆: ∆aa 201-338. Serial dilutions were spotted and cells were grown at 30°C for 4 days. See also Fig. EV3C.",
    "ncbi_link": "Slx5: 851549
Euc1: 855138"
  },
  {
    "caption": "(A) Euc1 Slx5-binding mutations impair Euc1 ubiquitylation. His-ubiquitin-modified proteins were enriched by denaturing NiNTA-PDs as described in Fig. 4E. 3FLAG-tagged Euc1 constructs were expressed from plasmids under the control of the ADH promoter. NiNTA-PD eluates were probed with FLAG and ubiquitin (P4D1) antibodies. Whole cell lysates (input) were probed with FLAG and Dpm1 antibodies.",
    "ncbi_link": "FLAG: 
ADH: 854068
Euc1: 855138"
  },
  {
    "caption": "(B) The Slx5-SIMs and Slx5-Md are required for Euc1 ubiquitylation. NiNTA-PDs for His-ubiquitin as in (A). All strains expressed wild-type 3FLAGEuc1 from plasmids under the ADH promoter and His-ubiquitin. Slx5 constructs were expressed from plasmids under control of the endogenous promoter. WBs were probed as described in (A), Slx5-levels were probed using an HA antibody. Asterisk denotes a non-specific band. Slx5-SIM*: SIMs 1-4 were mutated as described (Xie et al, 2010), for SIM5, aa 477-479 (IIV) were mutated to alanines. To avoid possible mislocalization by deletion of the Slx5-Md, which overlaps with a putative NLS (Westerbeck et al, 2014), an N-terminal NLS was fused to all constructs. See Appendix Fig. S7C for HU complementation.",
    "ncbi_link": "FLAG: 
His: 
ADH: 854068
Slx5: 851549
ubiquitin: 850620
Euc1: 855138"
  },
  {
    "caption": "(C) Euc1 Slx5-binding mutations (SBM1/SBM2) reduce/abolish ub-HSs and recruitment of Slx5 to ub-HSs. ChIP-qPCR for ub-K48 (top) or Slx5 (using Slx5 antibody, bottom) in euc1∆ ubx5∆ cells expressing the indicated constructs from plasmids under the control of the EUC1 promoter. Data represent means ± SD (n = 3). See also Appendix Fig. S7E-G.",
    "ncbi_link": "ubx5: 851930
EUC1: 855138
Euc1: 855138
euc1: 855138"
  },
  {
    "caption": "(D) Slx5-SIMs and the Slx5-Md are required for the formation of ub-HSs and recruitment of Slx5. ChIP-qPCR for ub-K48 (left) or Slx5 (anti-HA ChIP, right) in ubx5∆ cells or slx5∆ ubx5∆ cells complemented with plasmids expressing the indicated Slx5-constructs under control of the SLX5 promoter. Data represent means ± SD (n = 2). See also Appendix Fig. S7H.",
    "ncbi_link": "SLX5: 851549
slx5: 851549
Slx5: 851549
ubx5: 851930"
  },
  {
    "caption": "(A) Deletion of EUC1 does not lead to ub-HS adjacent gene deregulation, but rather widespread transcriptome changes. Total RNA isolated from WT and euc1∆ cells was polyA-enriched and sequenced (RNAseq, triplicates). Significance testing was based on the Wald test, see Materials and Methods for details. See also Appendix Fig. S8A for quantification of selected transcripts by qPCR.",
    "ncbi_link": "EUC1: 855138
euc1: 855138"
  },
  {
    "caption": "(B) RNAseq transcriptome analysis of EUC1 overexpression as in (A). ∆euc1 cells with pGAL-EUC1 or pEUC1-EUC1 (control) integrated at the URA3-locus (YIplac211) were grown to mid-log phase and 2% galactose was added for 3h. See also Appendix Fig. S8E.",
    "ncbi_link": "URA3: 856692
euc1: 855138
EUC1: 855138"
  },
  {
    "caption": "(C) EUC1 overexpression is toxic at elevated temperatures and upon exposure to the membrane fluidizing drug benzylalcohol. For (C, D, F), serial dilutions of the indicated strains were spotted and grown on YPD control (or selective media) plates or under conditions as indicated. See also Fig. EV4A-B.",
    "ncbi_link": "EUC1: 855138"
  },
  {
    "caption": "(D) EUC1 overexpression toxicity depends on DNA binding and transactivation. The indicated EUC1 alleles with endogenous or galactose-inducible promoters were integrated at the URA3 locus (YIplac211, euc1∆ background) and spotted on glucose control or galactose plates to induce EUC1 overexpression. See also Appendix Fig. S9A-C.",
    "ncbi_link": "URA3: 856692
EUC1: 855138
euc1: 855138"
  },
  {
    "caption": "(E) Aberrant binding of overexpressed EUC1 partially depends on Euc1 DNA binding. ChIP-qPCR of Euc1 after 3 hours galactose induction. Note that IP/input ratios of Euc1 signals are shown, also for the control locus (contr., TOS1 promoter) to highlight Euc1 binding at non-ub-HS sites. STI1-CIN5: intergenic region. TEC1-us: upstream (promoter) region. Data represent means ± SD (n = 3). See also Fig. EV4C-D.",
    "ncbi_link": "CIN5: 854193
STI1: 854192
TEC1: 852377
TOS1: 852459
EUC1: 855138"
  },
  {
    "caption": "(F) Simultaneous overexpression of SLX5 and SLX8 rescue EUC1 toxicity. Experiment as in (D), but with concomitant plasmid-borne overexpression (ADH promoter) of SLX5 and SLX8 (bottom panels) and on media selecting for SLX5/SLX8 plasmids. See also Fig. EV4E and Appendix Fig. S9D.",
    "ncbi_link": "ADH: 854068
SLX5: 851549
SLX8: 856852
EUC1: 855138"
  },
  {
    "caption": "EUC1 displays negative genetic interactions with genes involved in general and specific transcriptional regulation (A) and in particular with members of the Rpd3L histone deacetylase complex (B). For (A-D), serial dilutions of the indicated strains were spotted and grown on YPD control or selective media plates, or under conditions as indicated. Note that all strains used in (A-D) contained an extra copy of MED11,",
    "ncbi_link": "MED11: 855139
EUC1: 855138"
  },
  {
    "caption": "EUC1 displays negative genetic interactions with genes involved in particular with members of the Rpd3L histone deacetylase complex For , serial dilutions of the indicated strains were spotted and grown on YPD control or selective media plates, or under conditions as indicated. Note that all strains used in (A-D) contained an extra copy of MED11,",
    "ncbi_link": "MED11: 855139
EUC1: 855138"
  },
  {
    "caption": "For serial dilutions of the indicated strains were spotted and grown on YPD control or selective media plates, or under conditions as indicated. Note that all strains used contained an extra copy of MED11 (C) Plasmid-borne EUC1 complements genetic interactions with Rpd3L subunits. Empty vector (-) or a plasmid encoding EUC1 with its endogenous promoter were transformed in the indicated strains and spotted on selective media.",
    "ncbi_link": "MED11: 855139
EUC1: 855138"
  },
  {
    "caption": "For serial dilutions of the indicated strains were spotted and grown on YPD control or selective media plates, or under conditions as indicated. Note that all strains used contained an extra copy of MED11 (D) EUC1 and Rpd3S act in a common pathway which is redundant with Rpd3L. rco1∆ and eaf3∆ (Rpd3S) show similar phenotypes when paired with sds3∆ (Rpd3L) as euc1∆ and are epistatic with euc1∆.",
    "ncbi_link": "eaf3: 856134
MED11: 855139
rco1: 855097
sds3: 854725
EUC1: 855138
euc1: 855138"
  },
  {
    "caption": "The ability to form ub-hotspots is crucial for endogenous EUC1 function. The genetic interaction of EUC1 with SDS3 (Rpd3L complex) was rescued with plasmid-borne EUC1-alleles and serial dilutions were spotted on selective media. (-) denotes empty vector.",
    "ncbi_link": "SDS3: 854725
EUC1: 855138"
  },
  {
    "caption": "SLX5 also shows negative genetic interactions with SDS3 upon heat stress. Serial dilutions of the indicated strains were spotted on YPD and incubated as indicated. See also Appendix Fig. S12C-D. Note that all strains used in (A-C) contained an extra copy of MED11,",
    "ncbi_link": "MED11: 855139
SDS3: 854725
SLX5: 851549"
  },
  {
    "caption": "C-E. Western blot analysis for CCNA, CCNB, Cdk1 and GAPDH (loading control) protein expression in lysates from control (si-GFP) and p53-depleted (si-p53; si-p53_1) (C) MDA-MB-231 and CAL27 cell lines. Representative images are shown.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "C-E. Western blot analysis for CCNA, CCNB, Cdk1 and GAPDH (loading control) protein expression in lysates from control (si-GFP) and YAP-depleted (si-YAP; si-YAP_1) (D) MDA-MB-231 and CAL27 cell lines. Representative images are shown.",
    "ncbi_link": "YAP: 10413"
  },
  {
    "caption": "C-E. Western blot analysis for CCNA, CCNB, Cdk1 and GAPDH (loading control) protein expression in lysates from control (si-GFP) and TAZ-depleted (si-TAZ) (E) MDA-MB-231 and CAL27 cell lines. Representative images are shown.",
    "ncbi_link": "TAZ: 6901"
  },
  {
    "caption": "A. Primary human breast cancers of the METABRIC dataset were stratified according to high or low YAP activity signature [47] and by TP53 mutational status, and then the levels of the cycline signature score were determined in the four groups. Cyclin activity is significantly higher in mut-p53 tumors with high levels of the YAP signature, as visualized by box-plot. Signature scores have been obtained summarizing the standardized expression levels of signature genes into a combined score with zero mean [7]. The values shown in graphs are thus adimensional. The bottom and top of the box are the first and third quartiles, and the band inside the box is the median; whiskers represent 1st and 99th percentiles; values lower and greater are shown as circles (p<0.0001, n=701).",
    "ncbi_link": "p53: 7157
TP53: 7157
YAP: 10413"
  },
  {
    "caption": "B. Same as in A) using the YAP/TAZ activity signature of Zhang et al. (2009) (p<0.0001, n=701).",
    "ncbi_link": "TAZ: 6901
YAP: 10413"
  },
  {
    "caption": "C. Kaplan-Meier analysis representing the probability of disease-specific survival in mutant and wild-type p53 breast cancer patients from the METABRIC dataset stratified according high or low YAP/TAZ signature score. The log-rank test p-value reflects the significance of the association between high levels of the YAP/TAZ signature score and shorter survival in in mutant-p53 as compared to wild-type p53 patients (p<0.0001, n=251). All p-values were calculated with two-tailed Student's t-test.",
    "ncbi_link": "TAZ: 6901
p53: 7157
YAP: 10413"
  },
  {
    "caption": "A. SKBr3 and MDA-MB-468 cells knocked-down as indicated in the figure, were transiently transfected with pCCAAT-B2LUC (100 ng) or pmutCCAAT-B2LUC (100 ng) luciferase reporter vectors. Values are means + s.d. of three replicates from three independent experiments.",
    "ncbi_link": "LUC: "
  },
  {
    "caption": "B. RT-qPCR of CCNA, CCNB2 and cdk1 mRNA levels in SKBr3 cells upon transduction with si-GFP and si-YAP (left graph) or si-p53 (right graph). Values are means + s.d. of three replicates from three independent experiments.",
    "ncbi_link": "GFP: 
CCNA: 8900///890
CCNB2: 9133
cdk1: 983
p53: 7157
YAP: 10413"
  },
  {
    "caption": "C. H1299 transfected with the indicated siRNAs, were transiently transfected with pCCAAT-B2LUC (100 ng) luciferase reporter vector together with empty pcDNA3 or mutant p53R175H. Representative western blotting to control the transfections presented in the right panel. Values are means + s.d. of three replicates from three independent experiments.",
    "ncbi_link": "LUC: 
p53: 7157"
  },
  {
    "caption": "D. RT-qPCR of CCNA and cdk1 mRNA levels in H1299 cells upon transfection with si-GFP or si-YAP oligos and empty pCDNA3 or mutp53R280H expression vectors as indicated in the figure. Error bars represent mean + s.d., from three biological replicates. P-values are indicated in the figures; two-tailed Student's t-test was applied throughout.",
    "ncbi_link": "GFP: 
CCNA: 8900///890
cdk1: 983
p53: 7157
YAP: 10413"
  },
  {
    "caption": "A and B. Coimmunoprecipitation and western blot analysis from H1299 cell lysates showing endogenous YAP (A) and overexpressed GFP-YAP (B) bound to mutp53R273H (A) or to mutp53R175H (B). In (A) YAP protein was immunoprecipitated with a rabbit polyclonal antibody and rabbit IgG was used as negative control of IP. In (B) p53 protein was immunoprecipitated with a sheep polyclonal antibody and the total lysate from H1299 transfected with empty pCDNA3 vector was used in as negative control of IP.",
    "ncbi_link": "p53: 7157
YAP: 10413"
  },
  {
    "caption": "C and D. Immunoprecipitations of YAP protein and western blot analysis for p53 binding are performed from lysates of cancer cell lines expressing different mutant p53 proteins (described in Materials and Methods) (C) YAP protein was immunoprecipitated with a rabbit polyclonal antibody and the same amount of rabbit IgG was used as negative control of IP.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "G. Cell lysates from CAL27 cells transfected with si-GFP and si-NF-YB oligonucleotides were immunoprecipitated with rabbit polyclonal YAP. As specificity control, immunoprecipitations were performed with rabbit IgG.",
    "ncbi_link": "GFP: 
NF-YB: 4801"
  },
  {
    "caption": "H and I. ChIP analysis of mutant p53, YAP and H4 acetylated histone-bound chromatin from MDA-MB-468 cells on transduction with siRNAs oligos targeting endogenous YAP (siYAP) (H), NF-Y (siNF-YB) (I), or siGFP as a negative control (H and I). The experiment was performed in biological triplicates. The CCNA, CCNB2 and Cdk1 promoter occupancy was analyzed by RT-qPCR. Normalization was performed to the amount of input chromatin. The ChIP results were further normalised on the RT-qPCR of a region resulted negative for the recruitment of mutant p53 (Appendix Table S5). P-values were calculated with two tailed Student's t-test. Statistically significant results were referred with p-value<0.05.",
    "ncbi_link": "GFP: 
CCNA: 8900///890
CCNB2: 9133
Cdk1: 983
NF-YB: 4801
YAP: 10413"
  },
  {
    "caption": "A and B. Proliferation curves of SKBr3 cell line knocked-down for YAP (A) or p53 (B). si-GFP oligos are used as negative control.Cell viability analysis in A and B was determined by trypan blue dye exclusion staining, in C was determined by ATPlite luminescence analysis. All the values are means + s.d. of six replicates from three independent experiments.",
    "ncbi_link": "GFP: 
p53: 7157
YAP: 10413"
  },
  {
    "caption": "C. Viability of CAL27 cell line transfected with si-GFP or si-p53 oligos and empty vector or GFP-YAP construct, as indicated in the legend to the graph.Cell viability analysis in A and B was determined by trypan blue dye exclusion staining, in C was determined by ATPlite luminescence analysis. All the values are means + s.d. of six replicates from three independent experiments.",
    "ncbi_link": "GFP: 
p53: 7157
YAP: 10413"
  },
  {
    "caption": "A. CCNA and CCNB2 expression transcripts were analyzed by RT-qPCR in cDNA derived from tumours of control (saline) or zoledronic acid (ZA)-treated mice (ref. 31). N=3 mice per group. P-values were calculated with two-tailed t-test.",
    "ncbi_link": "CCNA: 12427///12428
CCNB2: 12442"
  },
  {
    "caption": "B. ChIP analysis of mutant p53 -bound chromatin from MDA-MB-231 cells treated or not with 1 µM cerivastatin (Cer) for 24h. The CCNB2 promoter occupancy was analyzed by RT-qPCR. Normalization was performed to the amount of input chromatin. The experiment was performed in biological triplicate. P-values were calculated with two-tailed t-test.",
    "ncbi_link": "CCNB2: 9133"
  },
  {
    "caption": "C. MDA-MB-231 cells treated with the indicated concentrations of Cer for 24h were transfected with pCCAAT-B2LUC (100 ng) luciferase reporter vector. Error bars represent mean + s.d., from three biological replicates. P-values are indicated in the figures;p-values were calculated with two-tailed t-test.",
    "ncbi_link": "LUC: "
  },
  {
    "caption": "D. CCNA, CCNB2 and Cdk1 expression transcripts were analyzed by RT-qPCR in cDNA derived from MDA-MB-231 (left panel) and SKBr3 (right panel) cell lines treated or not with 1 µM Cer for 48h. Error bars represent mean + s.d., from three biological replicates. P-values were calculated with two-tailed t-test. P-value<0.01.",
    "ncbi_link": "CCNA: 8900///890
CCNB2: 9133
Cdk1: 983"
  },
  {
    "caption": "F. CCNA, CCNB2 and Cdk1 expression transcripts were analyzed by RT-qPCR in cDNA derived from MDA-MB-231cell line treated or not with 30µM ZA for 48h. Error bars represent mean + s.d., from three biological replicates. P-values were calculated with two-tailed t-test. P-value<0.01.",
    "ncbi_link": "CCNA: 8900///890
CCNB2: 9133
Cdk1: 983"
  },
  {
    "caption": "G. Viability assay of siGFP and sip53 -MDA-MB-231 cells after treatment with increasing amounts of cerivastatin (0, 0.01, 0.1, 1 and 10 µM) for 48 h. Data are normalized to untreated. Error bars represent mean + s.d., from three biological replicates.",
    "ncbi_link": "GFP: 
p53: 7157"
  },
  {
    "caption": "(D and E) Growth comparisons of bir1∆-ad2 strains that contain (18 strains) or do not contain (28 strains) confirmed suppressor mutations as measured by area of colony growth after serial dilution. The mean (red line) is shown. 10-fold serial dilutions were made on YPAD plates containing either 0.1% DMSO (D) or 10µg/mL of benomyl (E).",
    "ncbi_link": "bir1: 853551
ad2: 853958"
  },
  {
    "caption": "(A) Serial dilutions on YPAD media at the permissive (25˚C) or restrictive (35˚C) temperatures for the ipl1-321 mutation. The suppressor mutations from the Dam1c (blue) were the only mutants that rescued viability at the restrictive temperature.",
    "ncbi_link": "ipl1: 855892"
  },
  {
    "caption": "(B) Serial dilutions of strains engineered with the indicated mutations were tested for rescue of BIR1 deletion. 10-fold serial dilutions on the indicated media are shown. dam1(S20D) rescues loss of CPC activity to a similar extent as a suppressor mutant in Duo1.",
    "ncbi_link": "BIR1: 853551
dam1: 853010
Duo1: 852819"
  },
  {
    "caption": "(A) Serial dilutions of strains engineered with the indicated mutations were tested for rescue of BIR1 deletion. 10-fold serial dilutions on the indicated media are shown. The met30-6 and cdc4-1 alleles are temperature sensitive. Two independent clones of each of these alleles are shown. The serial dilutions were performed at the permissive temperature (20˚C).",
    "ncbi_link": "BIR1: 853551
cdc4: 850539
met30: 854765"
  },
  {
    "caption": "(B) The amount of mNeonGreen-Sli15 (CPC member) located at kinetochores (Nuf2-mCherry) was measured in prometaphase. Sgo1 was depleted by placing it under a galactose-inducible promoter and switching to glucose-containing media (YPAD). Representative images are on the left. Scale bar is 2µm. Averages from 3 independent experiments are shown.",
    "ncbi_link": "Sgo1: 854240"
  },
  {
    "caption": "G) Quantification of the percentage of CD11b+CD45low microglia  containing  lipid droplets as Bodipy+ microglia  using flow cytometry in male mice  deficient in Stat1  (Stat1-/-) (n=4) and corresponding Stat1+/+ mice  (n=7) shows ischemia-induced increases in Stat1+/+ mice  (** p=0.0086) but not in Stat1-/- mice  (p=0.927) (Two-way ANOVA and Šídák's multiple comparisons test). Graph shows values of the non-ischemic  (-) and ischemic  (+) brain  hemispheres of individual mice  and the mean±SD.",
    "ncbi_link": "Stat1: 20846"
  },
  {
    "caption": "A) Representative zooms of WT MEFs transfected with GFP-tagged Miro1 and Miro2 (GFPMiro1 and GFPMiro2). Control is GFP fused to the first 70 amino acids of Tom70. Tom20 and catalase stain mitochondria and peroxisomes, respectively. Merge is of Miro (green) and catalase (magenta) with colocalisation shown as white. White arrowheads highlight an area where an isolated peroxisome is situated. B) Quantification of the extent of GFP signal on peroxisomes. Data information: B) One-way ANOVA with Newman-Keuls post hoc test was used for all comparisons (n=18 cells per condition over 3 independent experiments). *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001 in comparison to Control, respectively, and ## and ### denote p < 0.01 and p < 0.001 in comparison to GFPMiro1, respectively. Data are represented as mean ± SEM. Scale bar is 5 μm.",
    "ncbi_link": "GFP: 
Miro1: 55288
Miro2: 89941"
  },
  {
    "caption": "C) Pulldown of overexpressed Pex19 in Cos7 cells with a Pex19 antibody shows interaction with full-length Miro1, but not Miro1 lacking the transmembrane domain.",
    "ncbi_link": "Pex19: 19298"
  },
  {
    "caption": "E) Representative images of Miro1 truncation constructs expressed in DKO MEFs. Mitochondria and peroxisomes are stained with Tom20 and catalase, respectively. White arrowheads highlight an area where an isolated peroxisome is situated.F",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": ".F) Quantification of the extent of peroxisomal localisation of the Miro1 truncation constructs. Data information: F) One-way ANOVA with Newman-Keuls post hoc test was used for all comparisons (n=18 cells per condition over 3 independent experiments). *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001 in comparison to Control, respectively, and ## and ### denote p < 0.01 and p < 0.001 in comparison to GFPMiro1, respectively. Data are represented as mean ± SEM. Scale bar is 5 μm.",
    "ncbi_link": "Miro1: 55288"
  },
  {
    "caption": "G) Co-immunoprecipation of Miro1 truncation constructs and mycPex19 following transfection into Cos7 cells. GFP-tagged Miro1 truncation constructs were pulled down with GFP-Trap agarose beads and Pex19 was probed with myc antibody.",
    "ncbi_link": "myc: 
Pex19: 19298
Miro1: 55288"
  },
  {
    "caption": "B) Blind scoring of the number of long-range peroxisomal trafficking events in WT, Miro1KO and Miro2KO and DKO MEFs (n=42 cells over six independent experiments. Two different MEFs lines were used for each genotype). Data information: For B) a Kruskall-Wallis with a Dunn's correction posthoc test was used to test for significance. For B) no statistical difference between conditions was observed, unless stated. Data are represented as mean ± SEM.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "E) Representative blots of Miro1, Miro2 and actin from whole cell lysates of wild-type and Miro1-floxed ERT Cre-recombinase MEFs treated with and without 4-OH tamoxifen for 48 hours. Lysates were taken one day after the end of treatment.",
    "ncbi_link": "Cre-recombinase: 2777477
ERT: 2100
Miro1: 59040"
  },
  {
    "caption": "G) Representative blot of Miro1 and Miro2 following knockdown of either Miro1 or Pex14 in HeLa cells.",
    "ncbi_link": "Pex14: 5195
Miro1: 55288"
  },
  {
    "caption": "H) Quantification of long-range peroxisomal trafficking events (visualised with pxGFP) in HeLa cells transfected with scrambled, Miro1 and Pex14 siRNA, by blind scoring of a five-minute movie (n=18 cells over three independent experiments). Data information: For H) is a one-way ANOVA with Newman-Keuls post-hoc test. ** denotes p < 0.01. For H), no statistical difference between conditions was observed, unless stated. Data are represented as mean ± SEM.",
    "ncbi_link": "Pex14: 5195
Miro1: 55288"
  },
  {
    "caption": "A) Representative images of WT, Miro1KO, Miro2KO and DKO MEFs seeded onto Y-shaped fibronectin micropatterns stained for mitochondria (Tom20 in red) and peroxisomes (Catalase in white). Scale bar represents 10 μm. Data information: n = 60 cells over three independent experiments.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "B) Normalised cumulative distribution of mitochondria in WT, Miro1KO, Miro2KO and DKO MEFs. C) Distance at which 95% of mitochondria are distributed (Mito95) for all four genotypes of MEF. Data information: n = 60 cells over three independent experiments. For C) one-way ANOVA with Newman-Keuls post-hoc test was used to test for statistical significance. *** represents p < 0.001. Data are represented as mean ± SEM.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "D) Normalised cumulative distribution curves comparing the peroxisomal distribution from the centre of the cell to the periphery of WT, Miro1KO, Miro2KO and DKO MEFs. E) Bar graph comparing the average distance at which 95% of the peroxisomal signal is distributed (Perox95). Data information: n = 60 cells over three independent experiments. For E) a one-way ANOVA with Newman-Keuls post-hoc test was used to test for statistical significance. *** represents p < 0.001. Data are represented as mean ± SEM.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "A) Snapshots and tracks of pxDsRed signal in WT, Miro1KO, Miro2KO and DKO MEFs following live imaging at 1.5 seconds per frame for two minutes. B) Quantification of median net displacement of individual peroxisomes (pxDsRed signal) for WT, Miro1KO, Miro2KO and DKO MEFs (n=42 cells over six independent experiments. Two different MEFs lines were used for each genotype). Data information: For multiple comparisons in B) a one-way ANOVA with Newman-Keuls post-hoc test was used to test for statistical significance.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "F) Median net displacement of peroxisomes in DKO MEFs with and without myc-tagged variant 4 of Miro1 (mycv4) (n=12 cells per condition over three independent experiments). Data information: Student's t-test was used to calculate statistical significance. * and *** represent p<0.05 and p<0.001, respectively. Data are represented as mean ± SEM.",
    "ncbi_link": "myc: 
Miro1: 59040
v4: 59040"
  },
  {
    "caption": "A) Representative images of catalase staining (peroxisomes) in WT, Miro1KO, Miro2KO and DKO MEFs.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "B) Bar graph comparing average peroxisomal area of WT Miro1KO, Miro2KO and DKO MEFs ( n = 60 cells per condition over three independent experiments). Data information: Calculation of statistical significance in B) was a one-way ANOVA with Newman-Keuls post-hoc. *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001, respectively. Data are represented as mean ± SEM. Scale bar is 10 μm. Scale bar in zooms is 5 μm.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "C) Comparison of total peroxisomal number between WT, Miro1KO, Miro2KO and DKO MEFs. n = 60 cells per condition over three independent experiments. Data information: Calculation of statistical significance in C) was a one-way ANOVA with Newman-Keuls post-hoc. *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001, respectively. Data are represented as mean ± SEM. Scale bar is 10 μm. Scale bar in zooms is 5 μm.",
    "ncbi_link": "Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "D) Representative images of Control (GFP-tagged 1-70 of Tom70), GFPMiro1 and GFPMiro2 in WT MEFs stained with catalase (peroxisomes).",
    "ncbi_link": "GFP: 
Miro1: 59040
Miro2: 214952"
  },
  {
    "caption": "E) Representative images of Pex14 (peroxisomes) in DKO MEFs expressing either GFP (control) or GFP-tagged variant 4 of Miro1 (GFPv4).",
    "ncbi_link": "GFP: 
Miro1: 59040
v4: 59040"
  },
  {
    "caption": "F) Bar graph comparing average peroxisomal area of Control, GFPMiro1 and GFPMiro2 overexpressing WT MEFs (n=60 cells per condition over three independent experiments). Data information: Calculation of statistical significance in F) was a one-way ANOVA with Newman-Keuls post-hoc. *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001, respectively. Data are represented as mean ± SEM. Scale bar is 10 μm. Scale bar in zooms is 5 μm.",
    "ncbi_link": "GFP: 
Miro1: 55288
Miro2: 89941"
  },
  {
    "caption": "G) Comparison of average area of individual peroxisomes between DKO MEFs expressing either GFP (control) or GFP-tagged variant 4 of Miro1 (GFPv4) (n=30 cells per condition over three independent experiments). Data information: Statistical test used in G) was a two-tailed Student's t test. *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001, respectively. Data are represented as mean ± SEM. Scale bar is 10 μm. Scale bar in zooms is 5 μm.",
    "ncbi_link": "GFP: 
Miro1: 59040
v4: 59040"
  },
  {
    "caption": "C) Representative images of a Fis1-Drp1 PLA in DKO MEFs expressing either GFP, GFPv1 (GFP-tagged variant 1 of Miro1) or GFPv4 (GFP-tagged variant 4 of Miro1) n=30 cells per condition over three independent experiments). Scale bar is 10 μm. Red dots indicate interaction of Fis1 and Drp1. Blue is DAPI. D) Quantification of PLA fluorescent dots per cells between GFP, GFPv1 or GFPv4 transfected DKO MEFs (n=30 cells over three independent experiments). Data information: In D) a one-way ANOVA with a Newman-Keuls post-hoc test was used to calculate statistical significance. *, ** and *** denote p < 0.05, p < 0.01 and p < 0.001, respectively. Data are represented as mean ± SEM.",
    "ncbi_link": "GFP: 
Miro1: 59040
v1: 59040
v4: 59040"
  },
  {
    "caption": "B) Western blot analysis of HEL whole cell lysate after transfection with cDNA coding for JAK2WT or JAK2V617F, alone or cotransfected with cDNA coding for Mpl.",
    "ncbi_link": "JAK2: 3717"
  },
  {
    "caption": "C) Summary of the ratios of mature:immature Mpl for at least three independent (2 for the JAK2V617F transfection) blotting experiments under the protocol shown in (B). Based on two−tailed Student t−test statistical analysis, there is a significant difference (p = 0.0001) in the ratio of Mpl isoforms in cells transfected with JAK2WT by comparison with control cells. Differences were also statistically significant in HEL cells transfected with either JAK2V617F or JAK2L611V/V617F by comparison to controls (p = 0.0159 and p = 0.0009, respectively). The mature:immature ratio is also significantly higher in cells transfected with JAK2WT than in cells transfected with JAK2V617F or JAK2L611V/V617F (p < 0.01).",
    "ncbi_link": "JAK2: 3717"
  },
  {
    "caption": "D) Western blot analysis of K562 lysates after transfection with cDNA coding for Mpl, alone or cotransfected with cDNA coding for JAK2WT or JAK2V617F.",
    "ncbi_link": "JAK2: 3717
Mpl: 4352"
  },
  {
    "caption": "Confocal fluorescent images of HEL cells (JAK2V617F+/+) after immuno‐fluorescence labeling of endogenous Mpl (A), or after transient transfection with cDNA coding for a chimeric Mpl protein fused to mOrange2 (B).",
    "ncbi_link": "JAK2: 3717
Mpl: 4352"
  },
  {
    "caption": "C) Confocal fluorescence image of K562 cells (JAK2WT+/+) transiently transfected with cDNA coding for MplmOrange2. Red arrow in this image points to plasma membrane localization.",
    "ncbi_link": "JAK2: 3717"
  },
  {
    "caption": "D and E) Confocal fluorescent images obtained after transient expression of MplmOrange2 and immuno‐fluorescent labeling of endogenous JAK2 in K562 (D) or HEL (E) cells. Profiles of fluorescence (across individual cells and indicated by a white arrow) are showing a good colocalization of Mpl and JAK2WT in K562 cells at the plasma membrane (black arrow heads) but no colocalization have been observed between MplmOrange2 and JAK2V617F in HEL.",
    "ncbi_link": "JAK2: 3717
Mpl: 4352"
  },
  {
    "caption": "F and G) Confocal fluorescent images obtained after transient coexpression of MplmOrange2 and either JAK2WTmCitrine (F) or JAK2V617FmCitrine (G) in K562 cells. Profiles of fluorescence (white arrows) are showing a very good colocalization of MplmOrange2 with JAK2WTmCitrine, especially at the plasma membrane (black arrow heads), but a very poor colocalization with JAK2V617FmCitrine (grey arrow heads). Nuclei are labeled with Hoechst and scale bars = 5 µm. R: Pearson's correlation coefficient.",
    "ncbi_link": "JAK2: 3717
Mpl: 4352"
  },
  {
    "caption": "HEL (A) and K562 (B) cells treated with non‐targeting (NT) or anti‐JAK2 siRNA analyzed by western blot.",
    "ncbi_link": "JAK2: 3717"
  },
  {
    "caption": "C) Confocal live cell (upper panel), or fixed cells (lower left panel), imaging of K562 cells expressing MpleGFP or MplmKO2 treated with NT or anti‐JAK2 siRNA showing a difference of distribution of intracellular Mpl in the siRNA treated cells compare to the control cells. After treatment with anti‐JAK2 siRNA, Mpl strongly colocalizes with the ER marker, calnexin. This colocalization in treated vs non‐treated cells is quantified and shown in Figure C lower right panel. Nuclei are labeled with Hoechst and scale bars = 5 µm.",
    "ncbi_link": "JAK2: 3717
Mpl: 4352"
  },
  {
    "caption": "Intracellular Mpl pools partially colocalize with ER markers and colocalize with autophagic and lysosomal markers in K562 and HEL cells. A-M) Confocal fluorescent images obtained after transient expression of MplmOrange2 or MplmKO2 and indicated labeling in K562 (A-F) or HEL (G-M) cells. Plots at right of each image show fluorescence intensities for each emission spectrum at points along the line drawn across each image. Black arrows in the plots point to overlap between MplmKO2 and either ER‐tracker (C,I), or Sec31a (B,J) that marks ER exit sites. MplmOrange2 did not colocalize with markers for the Golgi (Golgin‐97) or early endosomes (EEA1) in either cell line. However, MplmKO2 colocalized greatly with autophagic (LC3) (E,L) and lysosomal (LAMP1) (F,M) markers. Nuclei are labeled with Hoechst and scale bars = 5 µm. R: Pearson's correlation coefficient.",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "Intracellular Mpl pools partially colocalize with ER markers and colocalize with autophagic and lysosomal markers in K562 and HEL cells. A-M) Confocal fluorescent images obtained after transient expression of MplmOrange2 or MplmKO2 and indicated labeling in K562 (A-F) or HEL (G-M) cells. Plots at right of each image show fluorescence intensities for each emission spectrum at points along the line drawn across each image. Black arrows in the plots point to overlap between MplmKO2 and either ER‐tracker (C,I), or Sec31a (B,J) that marks ER exit sites. MplmOrange2 did not colocalize with markers for the Golgi (Golgin‐97) or early endosomes (EEA1) in either cell line. However, MplmKO2 colocalized greatly with autophagic (LC3) (E,L) and lysosomal (LAMP1) (F,M) markers. Nuclei are labeled with Hoechst and scale bars = 5 µm. R: Pearson's correlation coefficient.",
    "ncbi_link": "Mpl: 4352///4352"
  },
  {
    "caption": "Confocal fluorescent images obtained after transient expression of Mpl tagged with mKO2 and miniSOG in K562 (A) and HEL (B) cells. Electron micrographs of K562 (C) and HEL (D) cells transiently expressing MplmKO2‐miniSOG. Dark precipitate indicates the presence of the miniSOG‐tagged Mpl protein after photo‐precipitation of DAB. White boxes indicate original location of higher magnification images with corresponding letters.",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "H) High magnification electron micrograph of HEL cells treated in the same conditions as Figure D, cells transiently expressing MplmKO2-miniSOG , showing different stage of formation of APs (black arrows numbered from stages 1-4). Scale bars = 5 µm (A-D) or 100 nm (E-H).",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "E) Western blot analysis of protein phosphorylation in HEL, K562Mpl‐mKO2 and K562Mpl‐mOrange2 cells after Tpo stimulation (50 ng/mL Tpo, 10 min).",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "A and B) Surface biotinylation and total lysates western blot analysis of HEL or K562Mpl‐mKO2 cells after treatments for 60 min with Tpo, ionomycin (I), PMA, Mon or A23187.",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "C) Total lysate, surface biotinylation and exosomal fraction western blot analysis of HEL and K562Mpl‐mKO2 cells treated with Mon or A23187 for 15 h.",
    "ncbi_link": "Mpl: 4352"
  },
  {
    "caption": "F) Total lysate and surface biotinylation western blot analysis of HEL cells overexpressing ATG5 K130R‐V5 6 h post‐transfection.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "G) Total lysate and surface biotinylation western blot analysis of HEL cells overexpressing either GRASP55-V5 or HA-STX5.",
    "ncbi_link": "GRASP55: 26003
STX5: 6811"
  },
  {
    "caption": "C - Whole cell lysates were prepared with TG2+/+ and TG2-/- MEFs infected or not for 48 h with C. trachomatis L2 in the presence or not of BP, and analyzed as in (A).",
    "ncbi_link": "TG2: 21817"
  },
  {
    "caption": "E - Cells were infected with C. trachomatis L2 (MOI=1) for 24 or 46 h. Where indicated, 40 μM CP4d was added 2 hpi. tgm2 transcripts were measured by real-time RT-PCR and normalized to actin transcripts following the ∆∆Ct method. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated at least four times. P-values of Student's ratio-paired t-test <0.05 are shown.",
    "ncbi_link": "actin: 
tgm2: 21817"
  },
  {
    "caption": "F - Cells were treated for 18 h with the indicated concentration of human recombinant IL-6 before measuring TG2 transcription relative to actin like in (E). The data are presented as relative mRNA levels compared to untreated cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated at least three times. P-values of Student's ratio-paired t-test <0.05 are shown.",
    "ncbi_link": "actin: 
TG2: 21817"
  },
  {
    "caption": "Cells were left uninfected or infected with C. trachomatis L2 in the presence of the indicated concentration of anti-IL-6 receptor antibodies. Forty-eight h later TG2 transcription relative to actin was measured like in (E). The data are presented as relative mRNA levels compared to uninfected/untreated cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated at least three times. P-values of Student's ratio-paired t-test <0.05 are shown.",
    "ncbi_link": "actin: 
TG2: 21817"
  },
  {
    "caption": "A - HeLa cells were pre-treated with the indicated concentrations of CP4d (or DMSO alone) for 2 h before being infected with L2incDGFP at MOI=0.15. Thirty hours later the cells were disrupted and bacterial titers (IFU=inclusion forming unit) were determined by re-infecting fresh HeLa cells as described in the methods. The mean ± SD of three independent experiments are shown. P-values of Student's paired t-test are indicated when <0.05.",
    "ncbi_link": "incD: 45091107"
  },
  {
    "caption": "B - HeLa cells were transfected with control siRNA or two siRNAs against TG2. Two days later, the efficiency of the silencing was assessed by western blot using anti-TG2 antibodies and anti-actin antibodies as loading control (bottom). Duplicate wells were infected with L2incDGFP and progeny was analyzed as in (A) (top). The mean ± SD of four independent experiments are shown. P-values of Student's paired t-test are indicated when <0.05.",
    "ncbi_link": "incD: 45091107
TG2: 7052"
  },
  {
    "caption": "A - MEFs were grown for 24 h culture medium complemented with the indicated concentration of glucose before being infected with L2 IncDGFP bacteria (MOI = 0.2). Cells were disrupted 30 h later and the bacterial titer determined by re-infecting fresh wild type cells. The mean ± SD of three independent experiments are shown.",
    "ncbi_link": "GFP: 
IncD: 45091107"
  },
  {
    "caption": "B - Cells were infected with C. trachomatis L2 (MOI=1) for 24 or 48 h. Where indicated 40 μM CP4d was added 2 hpi. GLUT-1 and GLUT-3 transcripts were measured by real-time RT-PCR and normalized to actin transcripts following the ∆∆Ct method. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated four times. P-values of Student's ratio-paired t-test are indicated when <0.05.",
    "ncbi_link": "actin: 
GLUT-1: 6513
GLUT-3: 6515"
  },
  {
    "caption": "C -Relationship between TGM2 and GLUT-1 (top) and GLUT-3 (bottom) expression across 265 HGSOCs. Expression comparisons were performed using Spearman's rank correlation test.",
    "ncbi_link": "GLUT-1: 6513
GLUT-3: 6515
TGM2: 7052"
  },
  {
    "caption": "D -HeLa cells were infected with C. trachomatis L2 (MOI=1) for 24 or 46 h. HIF-1α transcripts were measured by real-time RT-PCR and normalized to actin transcripts. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated three times. P-values of Student's ratio-paired t-test are > 0.05.",
    "ncbi_link": "actin: 
HIF-1α: 3091"
  },
  {
    "caption": "E - HeLa cells were transfected with control siRNA or two siRNAs against HIF-1α. Two days later, cells were infected with C. trachomatis L2 (MOI=1) for 48 h. The indicated transcripts were measured by real-time RT-PCR and normalized to actin transcripts. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated three times. P-values of Student's ratio-paired t-test are indicated when <0.05.",
    "ncbi_link": "actin: 
HIF-1α: 3091"
  },
  {
    "caption": "F - TG2-/- MEFs stably transformed or not with the indicated TG2 construct were infected for two days with C. trachomatis L2 (MOI=1). Mouse GLUT-1 transcripts were measured by real-time RT-PCR and normalized to mouse actin transcripts. The data are presented as relative mRNA levels compared to uninfected cells and shown as the mean ± SD. Each experiment was performed in duplicate and repeated three times. P-values of Student's ratio-paired t-test are indicated when <0.05.",
    "ncbi_link": "actin: 
GLUT-1: 20525
TG2: 21817"
  },
  {
    "caption": "C - The same experimental procedure as described in (B) was applied to HeLa cells treated for 48 h prior to ionomycin treatment (8 µM) with siRNA control or directed against TG2.",
    "ncbi_link": "TG2: 7052"
  },
  {
    "caption": "C - HeLa cells treated for 72 h with siRNA targeting GFPT1 or GFPT2 were lysed. After separation with SDS-PAGE, proteins were transferred to a membrane, probed with anti-GFPT and anti-actin antibody before revelation with HRP-conjugated secondary antibodies.",
    "ncbi_link": "GFPT1: 2673
GFPT2: 9945"
  },
  {
    "caption": "D - HeLa cells were transfected with control siRNA or siRNAs against GFPT or TG2. Two days later the cells were infected for the indicated times (MOI=0.3) before fixation, rupture of the cells and measurement of bacterial diameter. The mean diameter ± SD and p-values of Student's paired t-test on 4 independent experiments are shown.",
    "ncbi_link": "GFPT: 2673
TG2: 7052"
  },
  {
    "caption": "E - HeLa cells treated for 48 h with siRNA targeting GFPT1 or not (siCTRL) were infected with C. trachomatis (MOI = 0.15). Thirty hours later cells were fixed and analyzed by flow cytometry. The percentage of infected cells (top) and the mean fluorescence of the infected population (middle) ) ± SD are shown for at least four independent experiments. Duplicate wells were lysed and used to re-infect fresh HeLa cells to determine the bacterial titer (bottom). P-values of Student's ratio-paired t-test are indicated.",
    "ncbi_link": "GFPT1: 2673"
  },
  {
    "caption": "(C) All eight subunits of the CCT chaperonin complex were enriched in U2OS-A3A  samples. Proteins detected by MS are displayed by fold enrichment (log2) from U2OS-A3A cells compared to parental cells (x-axis), and by protein abundance within the  U2OS-A3A  samples (y-axis). Significantly enriched proteins (p<0.05 by one-tailed t-test, n=3) are denoted in dark blue. Components of the CCT complex  are highlighted and labeled.",
    "ncbi_link": "A3A: 200315"
  },
  {
    "caption": "(A) A3A co-precipitates  with CCT complex subunits. U2OS  and HepaRG cells with  dox-inducible A3A-HA  transgenes were treated with  dox prior to immunoprecipitation of HA. HA immunoprecipitates were analyzed by immunoblot with antibodies for  HA  and subunits of the CCT complex.",
    "ncbi_link": "HA: 
A3A: 200315"
  },
  {
    "caption": "(C) A3A interacts with CCT in  leukemia  cells. HA immunoprecipitation in  hematopoietic cell lines with inducible  A3A-HA  was analyzed by immunoblot. HA, CCT1, and CCT5  antibodies were used to evaluate co-precipitation of CCT subunits with  A3A.",
    "ncbi_link": "HA: 
A3A: 200315"
  },
  {
    "caption": "(A) CCT  co-precipitates with A3A but not A3B or  A3G. 293T cells were transfected with empty vector (V), A3A-HA, A3B-HA, or A3G-HA. CCT IP was performed from transfected cells and evaluated by immunoblot analysis using antibodies for CCT5 and HA.",
    "ncbi_link": "HA: 
A3A: 200315
A3B: 9582
A3G: 60489"
  },
  {
    "caption": "(B) A3A, but not other  APOBEC3 enzymes,  interacts with CCT complex subunits. After transfection of 293T cells with HA-tagged APOBEC3 expression plasmids, IP was performed with anti-HA  antibody and analyzed by  immunoblot  using antibodies to HA and CCT subunits. Arrows mark location of each APOBEC3  protein on HA immunoblot.",
    "ncbi_link": "HA: "
  },
  {
    "caption": "(A) Knockdown of one CCT complex member results in depletion of other CCT subunits. Following siCCT4 or siCCT7  transfection, cell lysates were evaluated by immunoblot for expression of additional CCT subunits by endogenous antibodies for CCT1, CCT4, CCT5, and CCT7. GAPDH  was used as a loading control.",
    "ncbi_link": "CCT4: 10575
CCT7: 10574"
  },
  {
    "caption": "(B) Decreased cell viability  upon CCT depletion and A3A expression. CCT4 (left) and CCT7 (right) subunits were depleted by siRNA transfection in U2OS  cells with dox-inducible  A3A transgenes. Immunoblot  analysis of cell lysates showed decreased expression of targeted CCT subunit, but no alteration in  A3A expression. Scr indicates non-targeted siRNA, used as control. Ku-86 is a loading control. Following siRNA transfection to deplete CCT subunits, U2OS-A3A  cells were treated with  dox. Viability  was determined by  colorimetric change after addition of a water-soluble tetrazolium salt. Percent viability  was normalized to untreated controls. Statistical analysis was performed using a paired two-tailed t-test, n=3 biological replicates; error bars, SEM.",
    "ncbi_link": "A3A: 200315
CCT4: 10575
CCT7: 10574"
  },
  {
    "caption": "(D) Viability of cells with catalytically inactive A3A. U2OS-A3A-C106S cells were induced with dox to express the catalytically inactive A3A mutant (C106S), depleted of CCT4  by siRNA, or combination. Cells were subsequently evaluated by live-dead staining assessed by FACS. Bar chart shows quantitation of FACS  results averaged over three biological replicates. Statistical analysis was performed using a paired two-tailed t-test, n=3; error bars, SEM. Immunoblot analysis of cell lysates showed decreased expression of CCT4 after siRNA targeting. Ku-86 is a loading control.",
    "ncbi_link": "A3A: 200315
CCT4: 10575"
  },
  {
    "caption": "(E) Increased DNA damage signaling upon CCT depletion and A3A expression. Depletion of CCT7 in K562-A3A  cells was achieved by siRNA targeting. Expression of A3A was induced by dox treatment. Intracellular  staining with anti-γH2AX  antibody was analyzed by flow cytometry. Bar chart shows quantification of FACS results obtained over three biological replicates. Statistical analysis was performed using a two-tailed t-test, n=3; error bars, SEM. Immunoblot  analysis of cell lysates showed decreased expression of CCT7  after siRNA targeting and A3A expression upon dox  treatment. Ku-86 is a loading control. **p-value <0.01, ***p-value <0.01, ****p-value <0.0001, n.s. non-significant.",
    "ncbi_link": "A3A: 200315
CCT7: 10574"
  },
  {
    "caption": "(C) Quantification of APOBEC3  mutational signatures among three tumor types that have previously been associated with high APOBEC3 activity. Breast, bladder, and cervical cancer samples from the TCGA database were divided into CCT-mutated and non-mutated genomes, as above. The number of mutations contributing to SBS 2 and SBS 13 in each tumor type was quantified and displayed as an average. Comparison by Wilcoxon rank sum test yielded p-values denoted.",
    "ncbi_link": "APOBEC3: 9582///200315"
  },
  {
    "caption": "A. Vps10yEGFP localization. Yeast cells carrying Vps10yEGFP and expressing the indicated vps35 alleles as the sole source of Vps35 were logarithmically grown in SC medium. Their vacuoles were labelled with FM4-64. Cells were harvested by brief centrifugation and immediately imaged by confocal microscopy. Single confocal planes are shown. A brightfield image was used to outline the cell boundaries (shown in the merged images). B. Co-localization of Vps10yEGFP and FM4-64 in cells from a was measured using Pearson's coefficient. 15 Confocal planes with 20 to 30 cells each from 3 independent experiments were analyzed. Means",
    "ncbi_link": "vps35: 853287
Vps35: 853287"
  },
  {
    "caption": "B. Influence of VPS35 variants on GLUT1. HK2 cells silenced for VPS35 were transfected with a plasmid carrying siRNA resistant wildtype or mutant forms of GFP-VPS35. GLUT1 was detected by fixation and immunofluorescence staining as in a. Maximum projections of image stacks (step size in z of 300 nm) are shown.",
    "ncbi_link": "GFP: 
VPS35: 55737"
  },
  {
    "caption": "C. Quantification of GLUT1 immunofluorescence in cells from B. Regions of interest (ROIs) corresponding to cells expressing the indicated VPS35 variants, and some regions outside the cells (background), were manually defined using ImageJ software. Total cell fluorescence was integrated and corrected for background fluorescence. 105 cells per condition stemming from 3 independent experiments were analyzed. The analysis was performed with 99% confidence: *** p < 0.001.",
    "ncbi_link": "VPS35: 55737"
  },
  {
    "caption": "D. Expression of Vps35 variants in cells from B was analyzed by SDS-PAGE and Western blot against Vps35. Tubulin served as loading control.",
    "ncbi_link": "Vps35: 55737"
  },
  {
    "caption": "(B) Bar graph summarizing the efficiency of single RNAi knockdowns for 28 out of the 30 TRs, and their effects in the reprogramming efficiency in comparison to control cells expressing scramble shRNA. The efficiency of each TR's knockdown (KD) does not correlate with its effect in reprogramming efficiency. The knockdown of 9 (Class III) out of the 28 TRs decreased the efficiency of the reprogramming in a statistically significant manner (unpaired two-tailed Student's t-test, p-value <0.05). Data are shown as mean ± SEM of at least two independent experiments. Class I corresponds to one TR inhibiting reprogramming, whereas Class II corresponds to 18 TRs having a weak or no effect in repogramming. Shown are the effects of 28 out of 30 TRs, because we did not succeed in knocking down Cphx and Phox2a.",
    "ncbi_link": "Cphx: 105594
Phox2a: 11859"
  },
  {
    "caption": "(E) Heatmap summarizing the most striking effects of double nine TRs KDs on the expression of the other TRs and on the expression of the Epcam and Lin28a pluripotency markers; the white color indicates no change in expression levels. The genes examined have been ranked in the heatmap according to their order of upregulation during reprogramming; Lin28a is the latest upregulated gene.",
    "ncbi_link": "Epcam: 17075
Lin28a: 83557"
  },
  {
    "caption": "(C) Shown is a bar graph depicting the effects of rescue experiments in reprogramming efficiency. MEFs undergoing reprogramming were knocked down using shRNAs for the endogenous Nanog or Irf6 expression and were co-infected with a vector expressing an shRNA-resistant human homologue of Nanog or Irf6 (hNanog OE, hIrf6 OE). Data are shown as mean ± SEM of two independent experiments.",
    "ncbi_link": "Irf6: 54139
Irf6: 3664
Nanog: 71950
Nanog: 79923"
  },
  {
    "caption": "(A) Immunostaining of CDC50A on Cdc50a knockdown neurons and controls. Accell Cdc50a siRNA pool was used to knock down Cdc50a in neurons for 7 days. CDC50A expression alongside neuronal processed was reduced after Cdc50a siRNA treatment. Scale bar, 10 µm.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(D) IHC of Cdc50a-RNAi neurons exhibited pSIVA colocalized with synapsin I, a general synapse marker. The dotted square was zoomed-in shown on the right side. Arrows indicated where pSIVA colocalized with synapsin I. Scale bar, 5 µm.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(D) Representative IHC images of CDC50A expression at synapses. Scale bar, 5 µm. Arrows indicate VGluT2+ RGC inputs. (E) Relative CDC50A expression at mCherry+ synapses in Cdc50a RNAi mice and controls. N = 3 for biological replicates, mean ± SD, * p < 0.05 by Student's t-test. ",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(F) PSIVA staining in the dLGN. Exposed PS was detected by pSIVA on RGC inputs in Cdc50a-RNAi mice. Scale bar, 5 µm. Arrows indicate pSIVA+/mCherry+ RGC inputs. (G) Quantification of the percentage of pSIVA+/mCherry+ RGC inputs in total mCherry+ RGC inputs. N = 4 for biological replicates, mean ± SEM, **p < 0.01 by Student's t-test. ",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(F) Maximum intensity z-projection images of vGluT2+ synapses in the core region of Cdc50a RNAi mice and controls. Right panel showed enlarged synapses in the boxed region. Scale bar, 20 µm.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(D) Images of CTB488 and CTB647 labeling of RGC inputs in the dLGN. Scale bar, 20 µm. (E) Quantification of CTB488+ inputs (non-infected areas) versus CTB647+ inputs (infected areas) in Cdc50a RNAi mice and controls. N = 3 for biological replicates, mean ± SEM, **** p < 0.0001, two-way ANOVA with Sidak's multiple comparisons test. ",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(A) The confocal images, 3D-rendered images and orthogonal views of microglia engulfing vGluT2+ synapses in controls and Cdc50a-RNAi mice. Scale bar, 10 µm.",
    "ncbi_link": "Cdc50a: 69981"
  },
  {
    "caption": "(A) IHC images for vGluT2 staining in the dLGN of microglial Gpr56 conditional knockout mice (Gpr56fl/fl; Cx3cr1cre/+) and controls (Gpr56+/+; Cx3cr1cre/+). Both mice were intravitreally injected with AAV2 carrying Cdc50a shRNA. The yellow squares indicated the AAV2 non-infected areas and the dotted outlines indicated the AAV2 infected areas. Scale bar, 200 µm.",
    "ncbi_link": "Gpr56: 14766
cre: 2777477
Cx3cr1: 13051
Cdc50a: 69981"
  },
  {
    "caption": "(B) Confocal images of vGluT2+ synapses in the AAV2 non-infected areas and infected areas of the dLGN. Scale bar, 20 µm. (C) Quantification of vGluT2+ synapses in the non-infected areas and infected areas of microglial GPR56 conditional knockout mice and controls. N = 4 for biological replicates, mean ± SD, * p<0.05, **** p < 0.0001 by two-way ANOVA with Sidak's multiple comparisons test. ",
    "ncbi_link": "GPR56: 14766"
  },
  {
    "caption": "C, Heatmap of DEGs between the Src-1/-2 dKO and WT fetuses  that are involved in the lung  development pathway (GO: 0030324).",
    "ncbi_link": "Src-1: 17977"
  },
  {
    "caption": "A and C, mRNA levels of Arg1  and Ass1  in fetal lungs  of mice  with different genotypes at 18.5 dpc; n=8 biological replicates in each group for panel A and 7 biological replicates in each group for panel C. One-way ANOVA followed by Tukey's multiple comparison test was used to analyze the data. The data are shown as the mean ± s.e.m., *P<0.05, ***P<0.001, ****P<0.0001, compared with the WT group.",
    "ncbi_link": "Arg1: 11846
Ass1: 11898"
  },
  {
    "caption": "E and F, Immunohistochemical staining  of ARG1  and ASS1  in fetal lungs  of WT and Src-1/-2 dKO mice  at 18.5 dpc. PBS  was used instead of the primary antibody as a negative control (NC). Scale bars: 50 μm in E and F.",
    "ncbi_link": "Src-1: 17977"
  },
  {
    "caption": "A and C, mRNA expression  of Arg1  and Ass1  in the lungs  of WT fetuses  at gestational ages  from 15.5 dpc to labor. n=6 biological replicates for each gestational age  in panel A; n=6 biological replicates for 15.5dpc, 17.5dpc, and labor group, n=5 biological replicates for 16.5dpc and 18.5dpc group in panel C. Kruskal-Wallis test followed by Dunn's multiple comparison test was used to analyze the data. The data shown are the mean ± s.e.m. **P<0.01, ****P<0.0001.",
    "ncbi_link": "Arg1: 11846
Ass1: 11898"
  },
  {
    "caption": "D and E, Histograms showing the content of arginine, ornithine, ADMA  and the ratio of arginine  to ADMA  in the fetal lungs  of WT mice  and Src-1/-2 dKO mice  at 18.5 dpc. Mann Whitney test was used to analyze the data in panel D, and unpaired t test was used to analyze the data in panel E. n=5 biological replicates for each group, and the data are shown as the mean ± s.e.m. The central band indicates the median, the boxes indicate the upper quartile and lower quartile, and the whiskers indicate maximum value and minimum value of the data. *P<0.05, **P<0.01, compared with the WT fetal lungs.",
    "ncbi_link": "Src-1: 17977"
  },
  {
    "caption": "B, Representative immunoblots  of ARG1 expression  in the fetal lungs  from the AAV-shArg1-injected group and the AAV-2/9-injected group. Densitometric  quantitation of scans of immunoblots  (normalized to tubulin) is also shown as a bar graph. Unpaired t test was used to analyze the data and n=3 biological replicates for each group. The data are shown as the mean ± s.e.m. **P<0.01 compared with the AAV-2/9-injected group.",
    "ncbi_link": "Arg1: 11846"
  },
  {
    "caption": "C, Representative immunoblots  and densitometric  quantitation of Ki67, caspase3  precursor (pro-caspase3) and cleaved caspase3 expression  in the fetal lungs  from the AAV-shArg1-injected group and AAV-2/9-injected group. Unpaired t test was used to analyze the data and n=3 biological replicates for each group. The data are shown as the mean ± s.e.m. **P<0.01 compared with the AAV-2/9-injected group; n.s indicates non-significance.",
    "ncbi_link": "Arg1: 11846"
  },
  {
    "caption": "E, Multiple immunofluorescence staining  and densitometric  quantitation of TUNEL  with PDPN  antibody (type I alveolar epithelial cells  marker) on sections of fetal lungs  from AAV-shArg1-injected mice  vs. AAV-2/9-injected mice. Blue: DAPI  (nuclei); Green: PDPN  (type I cells); Red: TUNEL  positive. Unpaired t test was used to analyze the quantitation data and n=3 biological replicates generated from the mean intensity of 3 randomly selected fields of view for each group. The data are shown as the mean ± s.e.m. ***P<0.001 compared with the AAV-2/9-injected group. F, Multiple immunofluorescence staining  and densitometric  quantitation of TUNEL  with LPCAT1  antibody (type II alveolar epithelial cells  marker) on sections of fetal lungs  from AAV-shArg1-injected mice  vs. AAV-2/9-injected mice. Blue: DAPI  (nuclei); Green: LPCAT1  (type II cells); Red: TUNEL  positive. Unpaired t test was used to analyze the quantitation data and n=3 biological replicates generated from the mean intensity of 3 randomly selected fields of view for each group. The data are shown as the mean ± s.e.m. ***P<0.001 compared with the AAV-2/9-injected group. Data information: Scale bars in E and F: 50 μm.",
    "ncbi_link": "Arg1: 11846"
  },
  {
    "caption": "C, Representative western blots  and quantitative analysis of CAP  expression  in the myometrium  of pregnant mice injected intraplacentally  with AAV-shArg1 or AAV  control viruses. Mann Whitney test was used to analyze CX43  and PTGFR  data and unpaired t test was used to analyze COX2  and OXTR data. n=4 biological replicates for CX43, COX2  and PTGFR  groups, and n=5 biological replicates for OXTR  group. The data are shown as the mean ± s.e.m. *P < 0.05.",
    "ncbi_link": "Arg1: 11846"
  },
  {
    "caption": "D, Representative  western blots  and quantitative analysis of   NF-κB  p-p65   (phospho  S536) and NF-κB p65 expression  in the myometrium  of pregnant mice injected intraplacentally  with AAV-shArg1 or AAV  control viruses. Unpaired t test was used and n=4 biological replicates for each group. The data are shown as the mean ± s.e.m. **P < 0.01.",
    "ncbi_link": "Arg1: 11846"
  },
  {
    "caption": "Chromatin immunoprecipitation  (ChIP) was performed with WT or Src-1/-2 dKO fetal lung  tissues using antibodies against GR  (B) Enrichment of these transcription factors at the GRE   or  C/EBPβ binding  sites within the Arg1  promoter were determined by quantitative PCR. Unpaired t test was used for panel B and n=6 biological replicates for each group. The data are presented as the mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001.",
    "ncbi_link": "Arg1: 11846
Src-1: 17977"
  },
  {
    "caption": "Chromatin immunoprecipitation (ChIP) was performed with WT or  Src-1/-2 dKO fetal lung  tissues using antibodies against SRC-1  (C), SRC-2 (D), or C/EBPβ (E). Enrichment of these transcription factors at the GRE   or C/EBPβ binding  sites within the Arg1  promoter were determined by quantitative PCR. Mann Whitney test was used for Panel C-E. n=6 biological replicates for each group. The data are presented as the mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001. F, Quantitative PCR results for GRE   and C/EBP binding  site using \"input\" (positive control) DNA without being immunoprecipitated  with any specific antibody. n=6 biological replicates for each group. The data are presented as the mean ± s.e.m.",
    "ncbi_link": "Arg1: 11846
Src-1: 17977"
  },
  {
    "caption": "p53 ChIPseq in MEFs of the indicated genotype treated with or without 10 µM nutlin-3a (Nutlin) for 16 hours. Shown are 2 kb regions surrounding the summit of the 468 p53 binding peaks called in Nutlin-treated p53+/+, but not p53-/- or p53EE/EE MEFs. For p53EE/EE MEFs three independent replicates are shown.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "RNAseq was performed with MEFs of the indicated genotype untreated or treated with 10 µM Nutlin for 16 hours. Shown are all Nutlin-regulated genes from the MSigDB gene set Hallmarks_P53_Pathway with a mean log2FC≥1 in p53+/+ cells. Shown are the z-transformed RNA expression values (FPKM).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "RNAseq data were subjected to gene set enrichment analysis (GSEA). Shown are enrichment plots for the indicated set of p53 downstream genes in pairwise comparisons of Nutlin-treated MEFs with the indicated p53 genotypes.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "Reverse transcription quantitative PCR (RTqPCR) analysis of p53 target genes in MEFs treated for 24 hours with 1 µg/ml doxorubicin (Doxo). Shown are expression values normalized to β-actin as mean ± SD (n=6).",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "MEFs were immortalized with the adenoviral oncogene E1A.12S (E1A MEF) and treated with 0.4 µg/ml Doxo for 17 hours. Apoptosis (Annexin V) was quantified by flow cytometry. +/+ and -/-: n=3; EE/EE: n=6. Western blots show expression of E1A and β-actin as loading control.",
    "ncbi_link": "E1A: 
E1A.12S: "
  },
  {
    "caption": "mRNA expression analysis (RTqPCR) of p53 target genes in thymocytes 6 hours after 6 Gy irradiation. Shown are expression values normalized to β-actin.",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "Observed and expected genotype distribution of newborn offspring from mating Mdm2+/-Trp53EE/+ mice (total number of pups n=185; contingency test P=0.0029). Observed and expected genotype distribution of newborn offspring from mating Mdm2+/-Trp53+/- mice (total number of pups n=435; contingency test P=0.912).",
    "ncbi_link": "Mdm2: 17246
Trp53: 22059"
  },
  {
    "caption": "Representative picture of an E9.5 Mdm2-/-Trp53EE/EE embryo (right) displays characteristic phenotypic abnormalities compared to an Mdm2+/-;Trp53EE/EE embryo (left).",
    "ncbi_link": "Mdm2: 17246
Trp53: 22059"
  },
  {
    "caption": "IHC for p53 and cleaved caspase-3 shows strong accumulation of p53EE protein and massive apoptosis in Mdm2-/-Trp53EE/EE compared to Mdm2+/-;Trp53EE/EE control embryos.",
    "ncbi_link": "Mdm2: 17246
Trp53: 22059"
  },
  {
    "caption": "Mdm2-/-Trp53-/- (double knock-out, DKO) MEFs were transduced with pInducer20-p53EE lentivirus to enable tetracyclin (Tet)-inducible expression of mouse p53EE. Induction of p53EE sensitized cells to apoptosis induced by 24 hour treatment with 1 µg/ml doxorubicin (Doxo) as detected by flow cytometry for Annexin V.",
    "ncbi_link": "Mdm2: 17246
Trp53: 22059
p53: 22059"
  },
  {
    "caption": "mRNA expression of p53 target genes was measured in cells from (A) relative to β-actin by RTqPCR following treatment with Tet ± 1 µg/ml Doxo. Expression of the pro-apoptotic p53 target genes Bbc3 (Puma) and Bax is not significantly induced. n=6.",
    "ncbi_link": "β-actin: 
Bax: 12028
Bbc3: 170770
Puma: 170770"
  },
  {
    "caption": "Western blot of E1A-MEFs with indicated genotypes treated with 10 µM Nutlin ± 0.4 µg/ml Doxo for 18 hours reveals induction of apoptosis (cCasp-3, cleaved caspase-3; cParp, cleaved Parp) in double-treated p53EE/EE MEFs in the absence of p53 target gene (p21, Mdm2) activation. *, 10 hours 0.4 µg/ml Doxo; **, 10 hours 0.2 µg/ml Doxo.",
    "ncbi_link": "E1A: 
p53: 22059"
  },
  {
    "caption": "mRNA expression of p53 target genes was measured in E1A MEFs of indicated genotype relative to β-actin by RTqPCR following combined treatment with 10 µM Nutlin and 1 µg/ml Doxo. n=12.",
    "ncbi_link": "E1A: 
β-actin: "
  },
  {
    "caption": "Western blot of p53EE/EE E1A-MEFs with indicated genotypes treated for 18 hours with 10 µM Nutlin, 0.4 µg/ml Doxo and 30-100-500 nM Ganetespib as indicated. Comb, combined treatment with 3 drugs for 18 hours. Pre, pre-treatment with ganetespib for 24 hours followed by combined treatment with Nutlin and Doxorubicin for 18 hours.",
    "ncbi_link": "E1A: 
p53: 22059"
  },
  {
    "caption": "Cell death measured by flow cytometry using propidium iodide exclusion in human lung adenocarcinoma H1299 cells with tet-inducible expression of human p53EE. Cells with overexpression of human p53EE mutant display a trend of increased cell death after treatment with 0.5 µg/ml Doxo.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Cell death measured by flow cytometry using propidium iodide exclusion in human lung adenocarcinoma H1299 cells with tet-inducible expression of human p53EE. Cells with overexpression of human p53EE mutant display a trend of increased cell death after treatment with 0.5 µg/ml Doxo. This effect is enhanced by addition of Nutlin and blocked by the pan-caspase inhibitor QVDOph, but not the ferroptosis inhibitor Ferrostatin-1 (Ferr) as control. (A) n=3; (B) n=2.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "mRNA expression analysis (RTqPCR) of p53 target genes following treatment with 0.5 µg/ml Doxo ± 10 µM Nutlin. KO, tet-induced H1299-pInd cells; EE, tet-induced H1299-pInd-p53EE cells; WT, H460 cells. mRNA expression was normalized to β-actin; n=3.",
    "ncbi_link": "β-actin: 
p53: 7157"
  },
  {
    "caption": "Mitochondrial membrane potential of control and p53EE expressing H1299 cells in the absence and presence of increasing concentrations of BID BH3 peptide. Treatment with the mitochondrial depolarizer CCCP is shown as a positive control; n=3.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "Apoptosis measured by flow cytometry using Annexin V in H1299 cells with tet-inducible expression of the indicated human p53 mutants; n=3.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "mRNA expression analysis (RTqPCR) of p53 target genes normalized to β-actin; n=3.",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "Kaplan-Meier survival plots for Eµ-Myc transgenic mice with different p53 genotype. Kaplan-Meier survival plots for wild-type recipient mice transplanted with AML1/ETO9a + NrasG12D-transduced fetal liver cells (5 donors/genotype).",
    "ncbi_link": "Myc: 
Nras: 18176
AML1: 861
ETO9a: 862
p53: 22059"
  },
  {
    "caption": "Enrichment of p53 shRNA-expressing Eµ-Myc;p53EE lymphoma cells under MAF treatment. Non-silencing control shRNA served as control. n=3.",
    "ncbi_link": "Myc: 
p53: 22059"
  },
  {
    "caption": "mRNA expression of p53 target genes was measured relative to β-actin by RTqPCR following treatment of Eµ-Myc lymphoma cells of indicated genotype with 3 µg/ml MAF. n≥3.",
    "ncbi_link": "β-actin: 
Myc: "
  },
  {
    "caption": "Kaplan-Meier survival plots for cyclophosphamide-treated versus untreated control mice transplanted with Eµ-Myc lymphoma cells of indicated genotype at day 0. Treatment started ~10 days later when peripheral lymph nodes became palpable. The time course of the experiment is illustrated in a scheme.",
    "ncbi_link": "Myc: "
  },
  {
    "caption": "Residual disease in the spleen of mice from (D) was quantified 24 hours and 7 days after therapy using a quantitative PCR assays with primers specific to the Eµ-Myc transgene (present only in lymphoma cells). Shown is the copy number of the Eµ-Myc transgene relative to a control locus present in all cells. Untreated Eµ-Myc mice (Myc tg) were used as positive control. Non-transgenic mice (no Myc tg) served as negative controls to define the detection limit. Significance was tested by t-test (two-sided, unpaired).",
    "ncbi_link": "Myc: "
  },
  {
    "caption": "Representative bioluminescence imaging (BLI) pictures of mice transplanted with AE9+Nras AML cells. Day 0 indicates the start of combination therapy with cytarabine (AraC) + doxorubicin (Doxo).",
    "ncbi_link": "AE9: 
Nras: 18176"
  },
  {
    "caption": "Kaplan-Meier survival plots for animals from (G). Statistical significance of differences calculated by Log-rank (Mantel-Cox) test between treated Eµ-Myc;p53EE/EE AML and all other groups is indicated in the table. C, untreated control; T, therapy (AraC+Doxo).",
    "ncbi_link": "Myc: 
p53: 22059"
  },
  {
    "caption": "Antibacterial competition assay. E. coli K12 recipient cells (W3110 gfp+, kanR) were mixed with the indicated EAEC attacker cells (1:4 ratio): WT, ∆T6SS-1 and ∆tle1-tli1 carrying pBAD18 and pBAD33 vectors, or producing the indicated proteins, and spotted on SIM 0.02 % arabinose agar plates for 4-h at 37°C. The image of a representative bacterial spot is shown. The number of recovered prey cells is indicated in the upper graph (in log of colony-forming units (cfu)). The black, dark grey and light grey circles indicate values obtained from three different spots, and the average is indicated by the bar. Western blot analysis of the production of Tle1V and Tle1∆1-26 V is shown in the inset. The experiment was performed in triplicate and a representative result is shown.",
    "ncbi_link": "T6SS-1: 
tle1: 
tli1: "
  },
  {
    "caption": "(C) Timelapse of ATP sensor FRET efficiency in the apGalts>PtcRNAi wing pouch after 10 μM antimycin A (ant.A) addition. Red dashed line indicates the position of the AP boundary.",
    "ncbi_link": "ap: 35509
Ptc: 35851"
  },
  {
    "caption": "(D, F) Mean FRET efficiency analyzed over time in the (D) dorsal anterior (DA) and ventral anterior (VA) sub-compartments or the (F) dorsal anterior (DA) and dorsal posterior (DP) sub-compartments of apGalts>PtcRNAi wing discs. Shaded regions indicate SD; dots represent the mean per timepoint; solid lines illustrate a fit of the mean data.",
    "ncbi_link": "ap: 35509
Ptc: 35851"
  },
  {
    "caption": "(I) Timelapse of ATP sensor FRET efficiency in apGalts > CiDN wing discs after 10 μM antimycin A addition.",
    "ncbi_link": "ap: 35509
Ci: 43767"
  },
  {
    "caption": "(J) Mean FRET efficiency measured over time in the dorsal and ventral compartments in apGalts > CiDN wings. Shaded regions indicate SD; dots represent the average per timepoint; solid lines illustrate a fit of the mean data.",
    "ncbi_link": "ap: 35509
Ci: 43767"
  },
  {
    "caption": "Gene expression of NOTCH3, HES1, HEY1, HEYL and the 17 recently identified targets were established by a real-time PCR panel assay in skeletal muscle of controls (n = 6), proband (II:1), parents (mother I:1, father I:2) and CADASIL patients (n = 3). Graph shows gene expression fold changes relative to controls and normalized on GAPDH (reference gene), expressed as mean of two experiments ± SEM. Among the 17 novel assayed target genes, RCAN2, ANGPT4, HP and SORBS were not detected in any sample and were therefore not reported. Green and red lines indicate 2.0 and 0.5 fold changes, respectively. Statistical significances and P-values are reported in Supplementary Table S1.",
    "ncbi_link": "GAPDH: 
ANGPT4: 51378
HES1: 3280
HEY1: 23462
HEYL: 26508
HP: 3240
NOTCH3: 4854
RCAN2: 10231
SORBS: 10174///8470///10580"
  },
  {
    "caption": "(C) Whole-mount immunohistochemistry with anti-neurofilaments antibody for visualization of peripheral nerves. In crmp2-/- embryos, the growth of ophthalmic branch of the trigeminal nerve is increased and axons are defasciculated (first and second row, arrowheads). Similarly, we detected increased growth and branching of lateral branches of spinal nerves in crmp2-/- embryos (third row, arrowheads). Trigeminal nerve (V) and its branches (Op - ophthalmic, Mx - maxillar, Md - mandibular) are indicated. Scale bars: 500 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(D, E) Quantification of areas innervated by ophthalmic branches of trigeminal ganglion and spinal nerve, normalized to WT littermates (each dot depicts one embryo). Area of ophthalmic branch in crmp2-/- was increased by 66% (p<0.05, n=10, 3 litters). For spinal nerves, total area in knockouts was increased by 45% (p<0.05, WT n=8, crmp2-/- n=7, 3 litters). Mean ± SD, * p<0.05, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(F) Growth of motor neurons from E11.5 - E12.5 WT and crmp2-/- spinal cord explants in microfluidic chambers. Excerpts from 14 hour time-lapse imaging are shown. Upon application of Sema3A into distal compartment, WT axons tend to stop or slow down their growth unlike crmp2-/- axons. Purple lines highlight the growth path of individual axons in a distal chamber. Scale bars: 100 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(G) Quantification of the fraction of growing (>50 μm) axons in one imaging field (WT: control 76.8±5.7%, Sema3A 57.7±10.6%, p<0.001, crmp2-/-: control 75.4±10.4%, Sema3A 75.4±6.7%, p=0.99), n=3 experiments per genotype, 7-8 explants per condition. Mean ± SD. *** p<0.001, 2-way ANOVA with Bonferroni's multiple comparisons test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(A) CRMP2 deficiency leads to callosal hypoplasia. Shortening of corpus callosum (arrowheads) is apparent in both sagittal (first row) and coronal sections (second row) of adult brains. Scale bars: 1 mm.",
    "ncbi_link": "CRMP2: 12934"
  },
  {
    "caption": "(B) Quantification of callosal length in 30-days old mice (P30, n=3, crmp2-/- is 80.8±5% of WT, p=0.003) and adult mice (n=3, crmp2-/- is 80.5±3% of WT, p=0.002), mean ± SD, * p<0.05, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(C) Labeling of adult corpus callosum with anti-neurofilaments antibody in sagittal sections. Outline depicts missing posterior part of the tract in crmp2-/- mice. Caudal part of the corpus callosum in WTs is located dorsally above the habenular commissure (hbc), while in crmp2-/- mice callosum terminates rostrally before reaching the hbc (arrows). PC indicates posterior commissure. Scale bars: 500 µm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(D) The growth of GFP-labeled callosal axons in the contralateral cortex at P6 (embryos were electroporated at E15.5). Note the disorganized paths of crmp2-/- axons. Scale bars: 200 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(F) Quantification of tortuosity of axons (WT n=6 pups, crmp2-/- n=3 pups) upon their exit from the callosal tract (WT 1.016±0.003 vs. crmp2-/- 1.044±0.012, p<0.001), mean ± SD, ***p<0.001, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(G) DiI-labeled callosal axons from P9 oblique brain sections and their reconstruction in Neurolucida 360 (WT n=6, crmp2-/- n=9). Scale bars: 200 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(H) Polar histograms of callosal axons reconstructed Note the broader range of axon growth angles in crmp2-/- mice.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(I) Left: schematic representation of polar histogram analysis by clustering the traced axons (WT n=6 pups, crmp2-/- n=9 pups) into 3 groups based on the growth angles. Right: proportion of axons growing in selected clusters (WT, 0°-±20°: 67.3±10.3%; ±20°-±40°: 21.2±5.3%; ±40°-±60°: 6.22±3.2%; crmp2-/-, 58.5±5%, p=0.047, 27.7±4.3%, p=0.022, 8.64±2.25%, p=0.11), mean ± SD, *p<0.05, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(A, B) (A) Coronal sections of P14 brains stained for calbindin and VgluT1. Infrapyramidal bundle (IPB) progresses into hippocampal CA3 region in both WT and crmp2-/- mice. Nuclei are counterstained with Hoechst 33342. (B) Details from depicted regions in (A), arrowheads show the course of IPB. Scale bars: 100 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(C, D) (C) Staining for calbindin shows unpruned infrapyramidal bundle in adult crmp2-/- mice. No VGluT2 signal in hippocampal CA3 region is present in WT and crmp2-/- suggesting mature synapses. Scale bars: 500 μm. (D) Details from depicted regions in (C), arrowheads show the course of IPB. Scale bars: 100 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(E, F) Staining for calbindin and VgluT1 shows mature synapses in the main bundle in both genotypes and in the IPB in crmp2-/- mice (arrowheads). Scale bars: 100 μm.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(G) Quantification of IPB index (length of the IPB vs. main bundle, WT 0.43±0.05, crmp2-/- 0.78±0.05, p<0.001) counted from adult coronal sections (WT n=4 mice, crmp2-/- n=5 mice). Mean ± SD, ***p<0.001, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(C) Quantification of VP (visual pruning) index (fluorescence intensity of pyramidal axons after vs. before the branch point). In WT animals after the pruning period, only a minor part of axons descends towards the pyramidal tract (WT: P9 0.65±0.09, adults 0.17±0.04, p=0.006). However, in crmp2-/- mice, corticospinal axons are still largely present, and their VP indexes are not significantly different between adult and P9 stages (crmp2-/-: P9 0.54±0.18, adults 0.62±0.27, p=0.24). Mean ± SD, **p<0.01, 2-way ANOVA with Bonferroni's multiple comparisons test. P9: n=3 pups/genotype, adults: n=5 mice/genotype)",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(A) Time-lapse imaging of DIV7 cultured hippocampal neurons before and after Semaphorin stimulation. Upper panel: Axon growth without Semaphorin stimulation. Middle panel: stimulation with Sema3A (0 hours) (1nM, n=669 axons for WT, 761 axons for knockout) causes retraction of both WT and crmp2-/- neurons. Lower panel: stimulation with Sema3F (5 nM, n=602 axons for WT, 955 axons for knockout) causes axon retraction in WT, but not in crmp2-/- neurons. Red triangles depict growing axons, yellow retracting axons and blue asterisks indicate steady non-growing axons. Scale bars: 100 μm (whole image field) and 50 μm (magnified).",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(C) Quantification of retracting axons (number of retracting vs. steady axons, 3 experiments). WT: control 13.4±5%, Sema3A 31.2±6% (p<0.001), Sema3F 36.9±8.7% (p<0.001); crmp2-/-: control 19.8±1.8%, Sema3A 28.5±4.4% (p<0.05), Sema3F 22.4±4.1% (p>0.99), mean ± SD are shown. ***p<0.001, *p<0.05, 2-way ANOVA with Bonferroni's multiple comparisons test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(A, B) Dendritic spine density in DiOlistically labeled DG granule cells is similar in WT and crmp2-/- mice at P30. In adults, however, spine density in crmp2-/- granule cells is increased comparing to WT. Scale bars: 5 μm. (C) Quantification of dendritic spine density in DG granule cells in the inner molecular layer (50 - 100 μm away from the soma). WT, P30: 12.5±2.2 spines/10 μm, adults: 9.95±2.3; crmp2-/-, P30: 12.86±2.1 (p>0.99), adults: 12.88±2.9 (p<0.001), mean ± SD, ***p<0.001, 2-way ANOVA with Bonferroni correction. P30: 3 animals/genotype, WT=61 dendrites, knockout=64 dendrites; adults: 3 animals/genotype, WT=41 dendrites, knockout=37 dendrites. ",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(D, E) Analysis of branching of DiOlistically labeled DG granule cell dendrites in adult WT and crmp2-/- mice (n=3 animals, ≥25 dendrites). Quantification of granule cell branching by Sholl analysis showed no significant differences (p>0.99). Scale bars: 50 μm, mean ± SEM, 2-way ANOVA with Bonferroni correction.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(F) Defects in synapse elimination in the inner molecular layer revealed by double immunostaining with PSD95 and VGluT2 antibodies (n=5 mice/genotype). GL indicates granule cell layer, IML/OML indicate inner/outer molecular layer, respectively. Density of colocalized PSD95/VGLuT2 puncta was counted. IML: WT 109±21, crmp2-/- 156±15 (p=0.004). OML: WT 281±38, crmp2-/- 297±80 (p=0.7). Scale bars: 10 μm, mean ± SD, *p<0.05, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(G) Spine density in DiOlistically labeled prefrontal cortex (PFC) is similar in WT and crmp2-/- mice in both juvenile and adult mice. Scale bars: 5 μm. (H) Quantification of dendritic spine density of PFC pyramidal neurons, basal dendrites (WT, juvenile: 8.63±1.44 spines/10 μm, adults: 7.3±1.4; crmp2-/-, juvenile: 9.05±1.73, p=0.97, adults: 6.98±1.53, p>0.99), mean ± SD, 2-way ANOVA with Bonferroni's multiple comparisons test. P25: n=3, ≥50 dendrites; adults: n=3, ≥50 dendrites. ",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(A - B) Ultrasonic vocalization was measured at P6, P8 and P12 (WT n=14 pups, crmp2-/- n=13 pups). In crmp2-/- mice, there is a significant decrease in the rate and duration of calls at P8 (call rate, WT 352±58/5 min, crmp2-/- 164±41/5 min, p=0.015; call duration, WT 9.52±2 ms, crmp2-/- 3.36±1 ms, p=0.011) and P12 (call rate, WT 46±16/5 min crmp2-/- 1.54±1.24/5 min, p=0.002; call duration, WT 0.68±0.35 ms, crmp2-/- 0.007±0.006 ms, p=0.002). Mean ± SEM, *p<0.05, t-test (P6, P8), Mann-Whitney test (P12). (C) Representative sonograms of the P8 mice. ",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(D) 3-chamber test (WT n=11 mice, crmp2-/- n=13 mice). In sociability phase, WT mice spent significantly more time with a social partner (stranger 1), unlike knockouts. (WT - stranger 1: 0.14±0.01, object: 0.07±0.007 (p=0.0001); crmp2-/- - stranger 1: 0.07±0.01, object: 0.04±0.006 (p=0.07)). In social novelty phase, when an object was substituted with a second social partner (stranger 2), both WTs and knockouts preferred novel mice to known mice. (WT - stranger 1: 0.03±0.006, stranger 2: 0.09±0.008 (p<0.0001); crmp2-/- - stranger 1: 0.02±0.004, stranger 2: 0.05±0.01 (p=0.02)). Mean ± SEM, *p<0.05, ***p<0.001, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "Elevated plus maze test (n=10 mice/genotype). (E) Total distance walked is similar in WT and crmp2-/- (WT 7.9±0.45 m, crmp2-/- 8.6±0.5 m, p=0.3). (F) Frequency of open arm (OA) visits is increased in crmp2-/- mice suggesting decreased anxiety. CA denotes closed arms, MID denotes the transition zone between arms, Total arm visits represents a sum of visits in all four arms. (CA frequency: WT 13.7±0.9/5 min, crmp2-/- 10.5±1.1/5 min, p=0.04; OA frequency: WT 7.7±0.8/5 min, crmp2-/- 14.6±1.7/5 min, p=0.002; MID frequency: WT 20.6±1/5 min, crmp2-/- 24.6±1.6/5 min, p=0.06 mean ± SEM, *p<0.05, ***p<0.001, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "Elevated plus maze test (n=10 mice/genotype). (G) duration of open arm (OA) visits is increased in crmp2-/- mice suggesting decreased anxiety. CA denotes closed arms, MID denotes the transition zone between arms, Total arm visits represents a sum of visits in all four arms. Total arm visits: WT 21.4±1/5 min, crmp2-/- 25.1±1.5/5 min, p=0.07; CA duration: WT 177±17 s., crmp2-/- 75.3±12.6 s, p<0.001; OA duration: WT 42±12.6 s, crmp2-/- 144.4±21 s, p<0.001; MID duration: WT 80.26±11.5 s., crmp2-/- 80.17±12.6 s., p=0.99), mean ± SEM, *p<0.05, ***p<0.001, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "(H, I) Y maze test (WT n=9 mice, crmp2-/- n=8 mice). Decreased alternations between arms of the maze indicates impaired working memory (number of visits, WT: 23.1±1.9, crmp2-/- 30.4±3.8, p=0.12; alternations, WT 68.8±2.5%, crmp2-/- 57.3±2.5%, p=0.006), mean ± SEM, *p<0.05, t-test.",
    "ncbi_link": "crmp2: 12934"
  },
  {
    "caption": "A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice treated with VSV (MOI,0.1) (A).",
    "ncbi_link": "IFN-β: 15977
IL-6: 16193
RKIP: 23980
TNF-α: 21926"
  },
  {
    "caption": "A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice treated with SEV (MOI,10) (B).",
    "ncbi_link": "IFN-β: 15977
IL-6: 16193
RKIP: 23980
TNF-α: 21926"
  },
  {
    "caption": "A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice transfected with poly(I:C) ( 1 μg/ml) (C).",
    "ncbi_link": "IFN-β: 15977
IL-6: 16193
RKIP: 23980
TNF-α: 21926"
  },
  {
    "caption": "D. Fluorescence-activated cell sorting (FACS) and TCID50 (50% tissue culture infective dose) assessing the proliferation level of VSV. RAW264.7 cells line stably overexpressed flag-RKIP was infected with VSV-eGFP at MOI of 1 for the indicated time. The fusion protein fluorophore were analyzed by FACS. Then fresh medium with the VSV-eGFP infection was serially diluted on the monolayer of HEK293 cells for 3-7 days and TCID50 was measured.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "E. FACS analysis the infection of wild type and RKIP-deficient peritoneal macrophage infected with VSV-eGFP at MOI of 1. The fresh medium with the VSV-eGFP infection 9 hr were collected for TCID50 assessing.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "A. Wide-type (RKIP+/+) and RKIP deficiency (RKIP-/-) chimera were intraperitoneally injected with VSV (1x107 pfu/g), 12 hours later, ELISA of IFN-β and IL-6 in serum (n=6 per group).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "B. Determination of VSV loads in organs by TCID50 assay 12 hours later after RKIP+/+ and RKIP-/- chimera mice (n = 6 per group) intraperitoneally injected with VSV (1x107 pfu/g).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "C. Real-time PCR analysis of IFN-β mRNA and VSV expression in liver from RKIP+/+ and RKIP-/- chimera mice 12 hours later intraperitoneally injected with VSV (1x107 pfu/g) (n = 6 per group).",
    "ncbi_link": "IFN-β: 15977
RKIP: 23980"
  },
  {
    "caption": "D. Pathology of wild type and RKIP deficient chimeric mice in response to VSV infection. Hematoxylin and eosin staining of liver and lung sections from mice in (A). Scale bar, 100 μm (left) or 50 μm (right).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "E. Real-time PCR analysis of IFN-β mRNA expression in peritoneal macrophages from RKIP+/+ and RKIP-/- chimera mice 12 hours after intraperitoneally injected with VSV (1x107 pfu/g) (n = 6 per group).",
    "ncbi_link": "IFN-β: 15977
RKIP: 23980"
  },
  {
    "caption": "F. Survival curve for 8 weeks-old wild type and RKIP deficient chimeras challenged with VSV (1x108 pfu/g, i.v.) (n=10 per group). *p<0.05 Wilcoxon Test .",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "A. Immunoblot analysis of p-TBK1, -IKKi, -IRF3, -P38, -JNK1/2, -ERK1/2 and -IκBα in lysates of RKIP+/+, RKIP+/- and RKIP-/- peritoneal macrophages stimulated with VSV (MOI, 0.1) for the indicated time.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "B. Immunoblot assay of RKIP+/+, RKIP+/- and RKIP-/- peritoneal macrophage cells treated with intracellular poly(I:C) (1 μg/ml).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "C. Immunoblot analysis of phosphorylated (p-) TBK1, IKKi, IRF3, P38, JNK1/2, ERK1/2 in peritoneal macrophage transfected with RKIP-specific or scrambled siRNA, followed by infection with VSV (MOI, 0.1). β-actin was used as a loading control.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "D. Immunoblot analysis of p- TBK1, -IKKi, -IRF3, -P38, -JNK1/2, -ERK1/2 and -IκBα in lysates of VSV-treated RAW264.7 cells stably over-expressing RKIP.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "E. Immunoblot analysis in lysates of RAW264.7 cells stably overexpressing RKIP treated with intracellular poly(I:C) (1 μg/ml).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "F. Luciferase activity in 293T cells transfected with plasmid encoding a luciferase reporter for IFN-β (IFN-β-luc) or ISRE (ISRE-luc), and an expression vector for RKIP (0, 50, 100, 200 ng each), together with plasmids encoding RIG-I CARD, TBK1, IKKi and IRF3 5D.",
    "ncbi_link": "luciferase: 
IFN-β: 3456
RKIP: 5037"
  },
  {
    "caption": "A. Immunoblot of extracts of RAW264.7 cells stably overexpressing flag-RKIP infected with VSV (MOI, 0.1) for the indicated times followed by immunoprecipitation (IP). WCL, whole cell lysates.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "B. Coimmunoprecipitation and immunoblot analysis of 293T cells transfected with vector for myc-RKIP alone or with the deletion mutants of TBK1. Numbers in parentheses indicate amino acids included in construct. FL, full length; KD, kinase domain; ULD, ubiquitin-like domain; SDD, α-helical scaffold domain; NBD, C-terminal domain.* indicates targeted band.",
    "ncbi_link": "RKIP: 5037
TBK1: 29110"
  },
  {
    "caption": "C. Immunoblot of 293T cells transfected with vector for myc-TBK1 together with plasmid for HA-GSK3β or HA-RKIP, followed by immunoprecipitation. * indicates targeted band.",
    "ncbi_link": "GSK3β: 2932
RKIP: 5037
TBK1: 29110"
  },
  {
    "caption": "D. In vitro kinase assay was carried out in the reaction mixture containing 2 mM ATP, 100 μM GST-RKIP or 100 μM GST-GFP and 5 μM flag-TBK1 at 30 °C for 30 min and then followed by immunoblotting with the indicated Antibody.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "A. Real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in RAW264.7 cells stably overexpressing flag-RKIP, flag-S109A and flag-S109D, followed by infection with VSV (MOI, 0.1).",
    "ncbi_link": "IFN-β: 15977
IL-6: 16193
RKIP: 23980
TNF-α: 21926"
  },
  {
    "caption": "C. FACS analysis of RAW264.7 cells stably overexpressing flag-RKIP, flag-S109A and flag-S109D infected with VSV-eGFP at MOI of 1.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "D. Immunoblot analysis of phosphorylated-TBK1, -IRF3, -P38 in lysates of RKIP+/+ or RKIP-/- bone marrow derived macrophages (BMDM) transfected with flag-RKIP, flag-S109A and flag-S109D, and then stimulated with VSV (MOI, 0.1).",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "B. BMDM cells were transfected with control or TBK1 siRNA. 72 hours after transfection, cells were analyzed by immunoblotting with antibody for phospho-RKIP or TBK1.",
    "ncbi_link": "TBK1: 56480"
  },
  {
    "caption": "C. Immunoblot analysis of RKIP phosphorylation in control or TBK1-/- mouse embryonic fibroblasts after VSV (MOI, 0.1) infection for the indicated times.",
    "ncbi_link": "TBK1: 56480"
  },
  {
    "caption": "D. Recombinant flag-tagged TBK1 was immunoprecipitated with anti-flag M2 beads in flag-TBK1 transfected 293T cells. Followed by in vitro kinase assay, which was carried out in the reaction mixture containing 2 mM ATP, 100 μM GST-RKIP or 100 μM GST-GFP together with 5 μM flag-TBK1 at 30 °C for 30 min. Assay mixtures were immunoblotted with the indicated antibody for phospho-RKIP, flag, GST or his.",
    "ncbi_link": "RKIP: 5037"
  },
  {
    "caption": "E. Immunoblot analysis of extracts of RAW264.7 cells stably overexpressing flag-RKIP, flag-S109A and flag-S109D, infected with VSV (MOI, 0.1) for the indicated times, followed by immunoprecipitation with anti-flag beads.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "F. BMDM cells were infected with VSV (MOI, 0.1) for the indicated times. The cell lysates were immunoprecipitated with anti-TBK1 (left) or anti-RKIP (right). The immunoprecipitates were analyzed by immunoblot with anti-RKIP or anti-TBK1 antibody. The levels of the endogenous RKIP, TBK1, and p-RKIP were detected by immunoblot analysis.",
    "ncbi_link": "RKIP: 23980
TBK1: 56480"
  },
  {
    "caption": "G. Co-immunoprecipitation and immunoblot analysis of 293T cells transfected with myc-TBK1 alone or with flag-RKIP, flag-S109A or flag-S109D.",
    "ncbi_link": "RKIP: 5037"
  },
  {
    "caption": "H. GST-pull down experiment was performed with 1 μg fusion protein GST-GFP, GST-his-RKIP or GST-his-S109D mixed with 20 μl precleared agarose beads in 800 μl reaction medium, followed by adding 1 μg flag-TBK1 and incubating at 4°C for 3 hours with gentle rotation. Pull down (1st-3th lane) and input samples (4th lane) were separated by SDS-PAGE followed by immunoblotting with anti-GST or anti-flag antibody.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": "I. Immunoprecipitation and immunoblot analysis of 293T cells transfected with indicated combinations of vector for myc-TBK1, flag-RKIP, flag-S109A, flag-S109D and HA-GSK3β or flag-GFP.",
    "ncbi_link": "GSK3β: 2932
RKIP: 5037"
  },
  {
    "caption": "J. In vitro kinase assay was carried out in the reaction mixture containing 2 mM ATP, 50 μM GST-TBK1 together with 100 μM GST-his-RKIP, 100 μM GST-his-S109D, 100 μM GST-his-S109A or 100 μM GST, respectively. React at 30 °C for 30 min. Then followed by immunoblotting with anti-p-TBK1or anti-GST antibody.",
    "ncbi_link": "RKIP: 23980"
  },
  {
    "caption": " B. Immunoblot analysis (IB) of GST-pulldown samples with deletion mutants of FUS‑NTD‑GST as baits with/without cell extract (C.E). ARID1A and BRG1 were used as tracers of SWI/SNF binding. Coomassie staining of recombinant proteins are shown in the lower panel. Amino acid numbers are indicated ",
    "ncbi_link": "GST: 
FUS: 2521"
  },
  {
    "caption": "C. Immunoblot analysis of proteins co-immunoprecipitated with nuclear extracted SWI/SNF from the model cell line HT1080 with overexpressed FUS-DDIT3-dsRED, EWSR1-FLI1-EGFP or dsRED are shown as representative immunoblots. Antibodies against BRG1, DDIT3 (FUS-DDIT3-dsRED), the C‑terminal parts of normal FUS and EWSR1, EZH2 and FLI1 (EWSR1-FLI1-EGFP) were used for detection. In order to directly quantify the fraction of bound and non-bound protein, relative amounts of protein for each IP‑sample were loaded on the gel, with consideration taken for dilutions during the immunoprecipitation procedure. I: input of nuclear extract, B: bound proteins, NB: proteins not bound. Immunoblots from all replicates are shown in the source data (with either dsRED- or EGFP‑tagged proteins expressed).",
    "ncbi_link": "dsRED: 
EGFP: 
DDIT3: 1649
EWSR1: 2130
FLI1: 2130
FUS: 2521"
  },
  {
    "caption": "D. Graphs showing the percentage of bound to total (bound + non‑bound) signal intensities from immunoblots for the fusion protein (FUS‑DDIT3 or EWSR1-FLI1), EWSR1, FUS and EZH2 in the model cell line HT1080 with overexpressed FUS-DDIT3-dsRED/-EGFP (n=4, circles), EWSR1-FLI1-EGFP (n=3, squares) or dsRED/EGFP (n=4, triangles). Mean ± SEM is shown with individual replicates indicated. Student's t-test, no significant changes, p>0.05. Original data for all quantifications, including p-values, are shown as source data.",
    "ncbi_link": "dsRED: 
EGFP: 
DDIT3: 1649
EWSR1: 2130
FLI1: 2130
FUS: 2521"
  },
  {
    "caption": "A. Immunoblot analysis (IB) of histone modifications in stably transfected HT1080 cell lines expressing EGFP, FUS‑DDIT3‑EGFP or EWSR1‑FLI1‑EGFP. Antibodies against H3K27Ac, H3K27me3, H3K4me3 and histone loading control H4 for detection of histone modifications and antibodies against EZH2 and loading control GAPDH to evaluate catalytic PRC2 amount. Immunoblot analysis with GFP antibody is shown to verify expression of FET fusion oncoproteins and EGFP. One representative immunoblot is shown. Graphs showing amount of protein (H3K27me3, H3K4me3, ratio H3K27me3/H3K4me3, H3K27Ac, and EZH2) quantified from immunoblots relative each corresponding loading control H4 or GAPDH, normalized to parental HT1080. Mean ± SEM is shown with individual replicates indicated by circles from two experiments with stable transfection and by squares from two experiments with transient transfection (24h and 48h , n=4. Student's t-test, ns= not significant, *p<0.05, **p<0.01, ***p<0.001. Original data for all quantifications, including p-values, are shown as source data.",
    "ncbi_link": "EGFP: 
DDIT3: 1649
EWSR1: 2130
FLI1: 2130
FUS: 2521"
  },
  {
    "caption": "Quantification of NANOG-positive iPSC colonies obtained after 14 days of OSKM induction in MEFs treated with either non-target or Kdm3b siRNA in FBS media. Values represent fold change over non-target control providing relative quantitation. Quantification of NANOG-positive iPSC colonies obtained after 12 or 14 days of OSKM induction in MEFs treated with either non-targeting or Kdm3b siRNA in KSR media. Values represent fold change over non-target control providing relative quantitation.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Quantification of NANOG positive colonies after retroviral expression of OSKM (Left) or OSK (Right) in MEF treated with non-targeting or siRNA targeting Kdm3. Nanog counts were performed on Day 16 for OSKM or Day 21 for OSK reprogramming. Values represent fold change over non-target control providing relative quantitation.",
    "ncbi_link": "Kdm3: 277250"
  },
  {
    "caption": "Immunoblot of H3K9me1/2 histone demethylase in WT or Kdm3b CRISPR targeted pre-iPSC clones. These pre-iPSCs carry a Nanog-GFP reporter. Parent line (WT), and two Kdm3b-KO clones using gRNA targeting either exon 1 (KO#1) or exon 2 (KO#2) are shown. RNA Polymerase II levels are the loading control.",
    "ncbi_link": "GFP: 
Kdm3b: 277250
Nanog: 71950"
  },
  {
    "caption": "Quantification of Nanog-GFP positive cells after 10 days of AA+2i treatment of WT or Kdm3b-deleted pre-iPSCs.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Immunoblot of H3K9 methylation levels upon addition of H3K9 methyltransferase inhibitor UNC0638 in WT or Kdm3b-KO pre-iPSCs.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Quantification of percent Nanog-GFP positive cells after 10 days of AA+2i or AA+2i with 5µM UNC0638 in WT or Kdm3b deleted pre-iPSCs.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Pearson correlation of transcripts per million (TPM) of WT and Kdm3b-KO pre-iPSC upon DMSO or AA+2i treatment for 2 or 10 days and mESC, reprogramming populations from Chronis et. al (2017), (labelled as CC).",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "k-means clustering of the union of DEG (FDR > 0.99) between day 2 and DMSO in WT and Kdm3b-KO pre-iPSCs. Values represent a log2-fold change of day 2 over DMSO. Key pluripotency genes are shown on the right. k-means clustering of the union of DEG (FDR > 0.99) between day 10 and DMSO in WT and Kdm3b-KO pre-iPSCs. Values represent a log2-fold change of day 10 over DMSO. Key pluripotency genes or epigenetic regulators are shown on the right.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Expression of Tet enzymes and Tdg during AA+2i treatment in WT or Kdm3b-KO pre-iPSCs. Error bars represent the standard deviation of two biological replicates from the RNA-Seq sample.",
    "ncbi_link": "Kdm3b: 277250
Tdg: 21665"
  },
  {
    "caption": "Quantification of percent Nanog-GFP cells of WT, Kdm3b-KO and Kdm3b-KO pre-iPSC clones expressing Tet1 catalytic domain (Tet1CD), Nanog, or both.",
    "ncbi_link": "Kdm3b: 277250
Nanog: 71950
Tet1: 52463"
  },
  {
    "caption": "Left - Quantification of percent Nanog-GFP positive colonies. Right - Total Nanog-GFP positive colonies obtained after ten days of AA+2i treatment in Tdg-depleted pre-iPSC (Tdg) or control (Empty).",
    "ncbi_link": "Tdg: 21665"
  },
  {
    "caption": "Quantification of percent Nanog-GFP positive cells of WT or Kdm3b-KO pre-IPSC clones expressing Nanog, Tet1CD, or Nanog+Tet1CD after 15 days of AA+2i or AA+2i with 4 or 5µM of UNC0638.",
    "ncbi_link": "Kdm3b: 277250
Nanog: 71950
Tet1: 52463"
  },
  {
    "caption": "Left - Heatmap of K-mean clustered 5hmC patterns in WT pre-iPSC with 5hmC profile of Kdm3b-KO pre-iPSC treated with AA+2i for 0, 2 or 10 days. Middle - Metaplot of 5hmC signal on day 10 between WT (orange) and Kdm3b-KO (black) for each cluster. Y-axis scale is in normalized coverage data (1x106/Total Count). Right - Illustration of 5hmC pattern in WT and Kdm3b-KO during AA+2i treatment.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Representative 5hmC profiles during AA+2i conversion of WT and Kdm3b-KO pre-iPSC.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Scheme for identifying genes with both misregulated 5hmC and expression. Heatmap of two-fold misregulated 5hmC and two-fold differential expression between WT and Kdm3b-KO after 10 days of AA+2i treatment (607 genes). Peaks are sorted by 5hmC signal in WT. RNA seq values represent a log2-fold change of day 10 over DMSO for either WT or Kdm3b KO pre-iPSCs.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Box plot of expression for genes that are two-fold misregulated 5hmC and expression between WT and Kdm3b-KO on day 10 (607 genes).",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "Representative 5hmC profiles during AA+2i conversion of WT and Kdm3b-KO pre-iPSC with POU5F1 binding in pre-iPSCs and mESCs. Loci were assigned to the nearest gene.",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "ChIP-PCR for POU5F1 during AA+2i reprogramming of WT and Kdm3b-KO pre-iPSCs. Values are fold change of enrichment between WT and Kdm3b KO (WT/Kdm3bKO).",
    "ncbi_link": "Kdm3b: 277250"
  },
  {
    "caption": "tSNE of Tet1, Tet2, Nanog, and Cdh1 expression in single cell RNA sequencing of MEF undergoing OSKM reprogramming from Tran et al 2019b. MEF, Reprogramming (REPROG), and mESCs cells are highlighted in red dotted lines. Specific reprogramming timepoints are highlighted within the reprogramming cluster in arrows. Color corresponds to log10 of transcript counts for each individual cell.",
    "ncbi_link": "Cdh1: 12550
Nanog: 71950
Tet1: 52463
Tet2: 214133"
  },
  {
    "caption": "Scheme for deriving Tet1 and Tet2 double knockout pre-iPSC lines. Tet1KO/KO Tet2fl/fl or Tet1WT/WT Tet2fl/fl MEFs were treated with retroviruses containing OSKM. Tet1KO/KO Tet2fl/fl or Tet1WT/WT Tet2fl/fl pre-iPSC clones were isolated and treated with either Adenoviral expressed Cre recombinase or Empty vector to generate a population of pre-iPSCs with Tet1KO/KO Tet2fl/fl, Tet1KO/KO Tet2KO/KO, Tet1WT/WT Tet2fl/fl, and Tet1WT/WT, and Tet2KO/KO. Scale bar, 50 μm.",
    "ncbi_link": "Cre recombinase: 2777477
Tet1: 52463
Tet2: 214133"
  },
  {
    "caption": "Quantification of percent Nanog positive cells by intracellular flow cytometry in each genotype as indicated of Tet1WT/WT Tet2fl/fl, Tet1WT/WT Tet2KO/KO, Tet1KO/KO Tet2fl/fl, and Tet1KO/KO Tet2KO/KO after 10 days of AA+2i treatment.",
    "ncbi_link": "Tet1: 52463
Tet2: 214133"
  },
  {
    "caption": "Time-course analysis of Oct4 expression and three lineage differentiation markers (Hand1, Brachyury and FGF5) during EB formation. It was quantified by qPCR, the relative expression of genes was calculated by the double delta Ct (ΔΔCt) method, normalized to the expression value at day 0. The relative expression data was represented as the heatmap.",
    "ncbi_link": "FGF5: 14176
Hand1: 15110
Oct4: 18999
Brachyury: 20997"
  },
  {
    "caption": "RBP ranking based on ES cell abilities to self-renewal (determined by colony formation (±LIF) and Oct4 expression) and exit-from-pluripotency (determined by AP staining, EB formation and marker genes expression) in the context of RBP KO. The expression value of Oct4, FGF5, Hand1 and Brachyury was represented as the relative level of these genes compared to their expressions in WT ES cells. The quantitation of other phenotypes, such as colony formation, AP staining and EB formation was manually defined.",
    "ncbi_link": "FGF5: 14176
Hand1: 15110
Oct4: 18999
Brachyury: 20997"
  },
  {
    "caption": "Immunofluorescence staining of Oct4 and hnRNPLL in WT and hnRNPLL-KO ES cells from two clones (H8 and G6). hnRNPLL was not expressed in either of the hnRNPLL-KO clones. DAPI stained the nuclei. Scale bar, 100 μm.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "EB formation from WT and the two hnRNPLL-KO ES cell clones. WT ES cell-derived EBs formed cystic structures by day 8 of differentiation; While both hnRNPLL-KO ES cell clones-derived EBs were more compact. Scale bar, 200 μm.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "AP staining of WT and both hnRNPLL-KO ES cell clones after LIF withdrawal. Scale bar, 200 μm.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Cumulative distribution showing the relative expression of WT-differentially expressed genes in hnRNPLL-KO ES cells during EB differentiation. Red lines and green lines represent the up- and down-regulated genes during EB differentiation of WT ES cells, while the black line stands for all expressed genes in WT and hnRNPLL-KO ES cells. Kolmogorov-Smirnov test was used to determine the significance. The relative expression ratio was log2-transformed before plotting.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Heatmap of key pluripotency and differentiation associated gene expression during EB formation from WT and hnRNPLL-KO clones (H8 and G6).",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Hematoxylin and eosin labeling and Oct4 immunohistochemical staining of teratomas derived from WT and hnRNPLL-KO ES cells (left). Representative Oct4-positive regions are shown. The percentage of Oct4 positive region (%) is plotted (right). The data represent the means ± SD, (n=3, from biological repeats). *P＜0.05; ***P＜0.001, T-test was used to determine the significance. Scale bar, 100 μm.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "AP staining of WT and hnRNPLL-overexpression ES cell lines maintained under ES cells culture conditions and colony formation assay. Scale bar, 200 μm. The data represent the means ± SD (n=3 biological repeats).",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Relative expression of Oct4 and Sox2 after hnRNPLL overexpression. The data represent the means ± SD (n=3, from biological repeats). ***P＜0.001. T-test was used to determine the significance.",
    "ncbi_link": "hnRNPLL: 72692
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "Birth rate of the different hnRNPLL genotypes, the birth rate of hnRNPLL-/- mice was significantly lower than that of WT hnRNPLL+/+ mice. The data represent the means ± SD. T-test was used to determine the significance.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Representative images of hnRNPLL+/+ and hnRNPLL-/- littermates at 3 weeks.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Survival curve analysis for hnRNPLL+/+, hnRNPLL+/-and hnRNPLL-/-mice (ten mice in hnRNPLL+/+/+/-group and seven mice in hnRNPLL-/-group).",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Genotypes and representative images of hnRNPLL+/+ embryo and retarded hnRNPLL-/- embryos at E11.5 which generated from hnRNPLL+/- intercrosses. Scale bar, 1mm.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Cumulative distribution of PSI with exon skipping events between WT and hnRNPLL-KO ES cells. Kolmogorov-Smirnov test was used to determine the significance.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Volcano plot of differential exon skipping events between WT and hnRNPLL-KO ES cells. Indicated AS events were labeled in purple (up-regulated) and green (down-regulated) with gene names.",
    "ncbi_link": "hnRNPLL: 72692"
  },
  {
    "caption": "Detection of Bptf and Tbx3 exon skipping events during EB formation in WT and hnRNPLL-KO ES cells (left) and in hnRNPLL-overexpression ES cells under ES cells culture conditions (right) by RT-PCR.OE, hnRNPLL overexpression.",
    "ncbi_link": "Bptf: 207165
hnRNPLL: 72692
Tbx3: 21386"
  },
  {
    "caption": "RT-PCR validation of Bptf exon24a and Tbx3 exon2a deletion in WT ES cells.",
    "ncbi_link": "Bptf: 207165
Tbx3: 21386"
  },
  {
    "caption": "AP staining of Bptf E24a KO or Tbx3 E2a KO ES cells maintained under normal ES cells culture conditions (upper). Scale bar, 200 μm. Colony formation assay of Bptf E24a KO or Tbx3 E2a KO ES cells under ES cells culture condition (lower left). The data represent the means ± SD (n=3, from biological repeats). ***P＜0.001. Colony diameter of Tbx3 E2a KO ES cells (lower right). The data represent the means ± SD (n＞80). ***P＜0.001. T-test was used to determine the significance.",
    "ncbi_link": "Bptf: 207165
Tbx3: 21386"
  },
  {
    "caption": "Relative expression of Oct4 and Rex1, determined by qRT-PCR. The data represent the means ± SD (n=3, from biological repeats). ***P＜0.001. T-test was used to determine the significance.",
    "ncbi_link": "Oct4: 18999
Rex1: 66932"
  },
  {
    "caption": "RT-PCR validation of Bptf and Tbx3 alternative exon deletion, separately in hnRNPLL-KO H8 cells (upper) and simultaneously in hnRNPLL-KO H8 cells (lower).",
    "ncbi_link": "Bptf: 207165
hnRNPLL: 72692
Tbx3: 21386"
  },
  {
    "caption": "AP staining of H8-Bptf or H8-Tbx3 exon-KO ES cells after LIF withdrawal. hnRNPLL-H8, hnRNPLL-KO ES cells; H8-Bptf KO, alternative Bptf exon was deleted in hnRNPLL-KO H8 cells; H8-Tbx3 KO, alternative Tbx3 exon was deleted in hnRNPLL-KO H8 cells; H8-Bptf/Tbx3 KO, alternative Bptf or Tbx3 exons were simultaneously deleted in hnRNPLL-KO H8 cells. Scale bar, 200 μm.",
    "ncbi_link": "Bptf: 207165
hnRNPLL: 72692
Tbx3: 21386"
  },
  {
    "caption": "Colony formation assay of H8-Bptf or H8-Tbx3 exon-KO ES cells after LIF withdrawal. The data represent the means± SD (n=3, from biological repeats).",
    "ncbi_link": "Bptf: 207165
Tbx3: 21386"
  },
  {
    "caption": "Hematoxylin and eosin labeling of teratomas derived from WT and H8-Bptf or H8-Tbx3 exon-KO ES cells. The blue triangle represent ectoderm, the dark one represent mesoderm and the green one represent endoderm. Scale bar, 100 μm.",
    "ncbi_link": "Bptf: 207165
Tbx3: 21386"
  },
  {
    "caption": "Oct4 immunohistochemical staining of teratomas derived from WT and H8-Bptf or H8-Tbx3 exon-KO ES cells. Representative Oct4-positive regions are shown (left). Scale bar, 100 µm. The percentage Oct4-positive region (%) is shown (right). The data represent the means± SD (n=3 biological repeats). **P＜0.01; ns, not significant. T-test was used to determine the significance.",
    "ncbi_link": "Bptf: 207165
Tbx3: 21386"
  },
  {
    "caption": "(C) Western blot analysis using anti-HA antibody after coimmunoprecipitation of ISWI1-3XFlagHA fusion protein. Non-transformed cells (WT) of the same strain were used as the negative control. 1% of the total lysate was loaded as Input and 20% of co-immunoprecipitated samples were loaded on 12% SDS gel.",
    "ncbi_link": "Flag: 
HA: 
ISWI1: 5017390///5017389"
  },
  {
    "caption": "(D) Volcano plot illustrating the distribution of proteins identified in label-free MS in WT Vs ISWI1-3XFlagHA. Significantly abundant proteins (fold change ≥ 4) are highlighted in orange.",
    "ncbi_link": "Flag: 
HA: 
ISWI1: 5017390///5017389"
  },
  {
    "caption": "(E) Western blot analysis using anti-HA and anti-GFP antibodies after coimmunoprecipitation of Ptiwi01-3XFlagHA fusion protein co-transformed with ISWI1-GFP. Non-transformed cells (WT) of the same strain and ISWI1-GFP fusion protein transformation were used as negative controls. 1% of the total lysate was loaded as Input and 20% of co-immunoprecipitated samples were loaded on 10%SDS gel.",
    "ncbi_link": "GFP: 
ISWI1: 5017390///5017389"
  },
  {
    "caption": "(D) Flag‐TEX10 was expressed with HA‐PELP1 in HeLa cells, captured on Flag‐beads and proteins were immunoblotted as indicated.",
    "ncbi_link": "TEX10: 54881"
  },
  {
    "caption": "(E) HA‐TEX10 was expressed, captured on HA‐beads and associated proteins were probed for the presence of endogenous WDR18 using immunoblotting. The inputs represent 2.5% of the total cell lysate.",
    "ncbi_link": "TEX10: 54881"
  },
  {
    "caption": "(B) HeLa cells were transfected with siRNA duplexes targeting PELP1, TEX10, WDR18, MDN1 or a control siRNA as indicated. Downregulation of the respective proteins was analysed by western blotting as indicated (WB, three lower panels). At 72 h after transfection, cells were pulse labelled with 32P‐orthophosphate for 1 h and chased for 2.5 h. RNA was separated on a denaturing agarose gel and detected by ethidium bromide (EtBr) staining and autoradiography after drying of the gel.",
    "ncbi_link": "MDN1: 23195
PELP1: 27043
TEX10: 54881
WDR18: 57418"
  },
  {
    "caption": "(C) The signal intensities of the 28S and 32S rRNA forms were quantified by phosphoimager analysis and the ratio of 28S:32S rRNA was calculated. Values represent the average of four (two for siMDN1) independent experiments. Error bars indicate s.d.",
    "ncbi_link": "MDN1: 23195"
  },
  {
    "caption": "(D) PELP1 is associated with ITS2‐containing RNA species. Endogenous PELP1 was immunoprecipitated from HeLa cells. In total, 10% of the immunoprecipitated material was analysed by western blotting (lower panel). The remaining material was used for RNA isolation and cDNA synthesis. The cDNA was used as template for PCR amplification using primers within the ITS2/28S region or GAPDH as a control. Input corresponds to 10% of the cell lysate. Vertical line in the upper panel indicates removal of irrelevant adjacent lanes.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "(F) Nucleolar export of pre‐60S particles is strongly compromised in cells depleted of PELP1, TEX10, WDR18, MDN1 or SENP3. HeLa cells expressing YFP‐RpL27 from a tetracycline‐inducible promoter were transfected with the indicated siRNAs. After 24 h, expression of YFP‐RpL27 was induced and 72 h later the localization of RpL27 was monitored. Pictures were taken using identical exposure times.",
    "ncbi_link": "MDN1: 23195
PELP1: 27043
SENP3: 26168
TEX10: 54881
WDR18: 57418"
  },
  {
    "caption": "(E) HeLa cells were depleted of endogenous PELP1 and reconstituted with siRNA resistant constructs expressing either wild‐type HA‐tagged PELP1 or a Flag‐tagged PELP1-SUMO2 fusion protein. The localization of the respective proteins was monitored by indirect immunofluorescence using either anti‐HA‐ or anti‐Flag‐antibodies.",
    "ncbi_link": "PELP1: 27043"
  },
  {
    "caption": "Representative images (A) and cfu quantification (B) of Shigella WT or ΔipaB mutant strain bound to HeLa cells pre-treated or not with arsenite. Ruffle formation induced by Shigella WT in panel (A) is indicated by white arrowheads",
    "ncbi_link": "ipaB: 876451"
  },
  {
    "caption": "Cfu quantification of Shigella WT or ΔipaB mutant strain bound to HeLa cells pre-treated with anisomycin or DMSO (control)",
    "ncbi_link": "ipaB: 876451"
  },
  {
    "caption": "Representative images (D) and cfu quantification (E) of Shigella WT or ΔipaB mutant bound to HCT-8 cells pre-treated or not with arsenite",
    "ncbi_link": "ipaB: 876451"
  },
  {
    "caption": "Representative image cf and  qRT-PC quantification of intracellular Shigella in HeLa cells transfected with ASM siRNA or control siRNA and pre-treated or not with arsenite prior to infection",
    "ncbi_link": "ASM: 6609"
  },
  {
    "caption": "Cfu quantification of intracellular Shigella in HeLa cells transfected with p38 siRNA or control siRNA and pre-treated or not with arsenite prior to infection",
    "ncbi_link": "p38: 5603///6300///5600///1432"
  },
  {
    "caption": "Cfu quantification of intracellular Shigella in HeLa cells transfected with p38 siRNA or control siRNA and pre-treated or not wit anisomycin prior to infection",
    "ncbi_link": "p38: 5603///6300///5600///1432"
  },
  {
    "caption": "Representative images (G) and cfu quantification (H) of bacteria bound to HeLa cells pre-treated or not with arsenite followed by incubation with Salmonella mutant strains ΔfliC, ΔfliC/pFliC or ΔflhC for 10 min",
    "ncbi_link": "flhC: 1253445
fliC: 1253480
FliC: 1253480"
  },
  {
    "caption": "Schematic representation of the experimental design for reinfection experiments. Cells were infected with Shigella-mCherry (primary infection) or mock-treated. At 3 hpi, cells were re-infected with Shigella expressing GFP (secondary infection). Secondary infection was analyzed at 0.5 hpi (i.e. 1 h after addition of bacteria to cells) Representative image and cfu quantification of re-infection assays with Shigella W of HeLa cells primarily infected with Shigella WT or ΔipaB/Inv mutant strain, or mock-treated",
    "ncbi_link": "ipaB: 876451"
  },
  {
    "caption": "Representative image and cfu quantificatio of re-infection assays wit Salmonella W of HeLa cells primarily infected with Shigella WT or ΔipaB/Inv mutant strain, or mock-treated",
    "ncbi_link": "ipaB: 876451"
  },
  {
    "caption": "Representative images (F) and cfu quantification (G) of the re-infection assays with Salmonella ΔfliC, ΔfliC/pFliC or ΔflhC mutant strains in HeLa cells primarily infected with Shigella WT or mock-treated",
    "ncbi_link": "flhC: 1253445
fliC: 1253480
FliC: 1253480"
  },
  {
    "caption": "Schematic representation of the experimental design for reinfections upon knockdown or inhibitor treatment. I and J. Representative images (I) and cfu quantification (J) of the secondary infection with Shigella WT, in cells transfected with ASM siRNA or control siRNA",
    "ncbi_link": "ASM: 6609"
  },
  {
    "caption": "Cfu quantification of the secondary infection with Shigella WT in HeLa cells followin transfectio with MAPK p38 siRN",
    "ncbi_link": "MAPK p38: 5603///6300///5600///1432"
  },
  {
    "caption": "B Phos‐tag gel following complete conversion of Ub to phosphoUb, using GST‐PhPINK1. A Ser65 mutant Ub is not modified.",
    "ncbi_link": "Ub: 286839///444874///615199///281370"
  },
  {
    "caption": "B Pull‐down assays with the Lys63‐specific TAB2 NZF against different tetraUb (Ub4) species are shown. Phosphorylation of K63 Ub4 does not prevent binding to TAB2 NZF. Met1‐linked tetraUb does not interact with TAB2 NZF, independent of Ser65 phosphorylation.",
    "ncbi_link": "Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "(F-G) Expression of Hif1α was modulated with overexpression or sh-RNA-mediated knockdown via a retrovirus system during reprogramming (F). The numbers of Oct4GFP+ colonies were determined on day 15 (G).",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "(H-I) Expression of Pdk1/2 was modulated with a retrovirus system, and oligomycin (1 µM) and 2-DG (5 mM) were used during reprogramming (H). The numbers of Oct4GFP+ colonies were determined on day 15 (I).",
    "ncbi_link": "Pdk1: 228026"
  },
  {
    "caption": "(D) The expression of Bmi1, Ctcf, Ezh2, Kdm2b, or Wdr5 was modulated with overexpression or sh-RNA-mediated knockdown via a retrovirus system during reprogramming. AP+Oct4GFP- and AP+Oct4GFP+ colonies were counted on day 15.",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "During reprogramming with mES medium, Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5 were overexpressed simultaneously with the four Yamanaka factors (OKMS+5F) or Oct4 (O+5F). All factors were delivered simultaneously via a retrovirus system on day 0 and 1. Reprogramming with only Yamanaka factors (OKMS) or Oct4 (O) served as control. The expression of pluripotency markers was determined with qPCR on day 6 during reprogramming (E).",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "During reprogramming with mES medium, Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5 were overexpressed simultaneously with the four Yamanaka factors (OKMS+5F) or Oct4 (O+5F). All factors were delivered simultaneously via a retrovirus system on day 0 and 1. Reprogramming with only Yamanaka factors (OKMS) or Oct4 (O) served as control. The numbers of Oct4GFP+ colonies were determined on day 15 (F).",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "During reprogramming with mES medium, Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5 were overexpressed simultaneously with the four Yamanaka factors (OKMS+5F) or Oct4 (O+5F). All factors were delivered simultaneously via a retrovirus system on day 0 and 1. Reprogramming with only Yamanaka factors (OKMS) or Oct4 (O) served as control. The histone methylation on core pluripotency loci was determined on day 6 with ChIP-qPCR (G).",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "(A) The enrichment of HIF1α, SNAI2, TWIST1/2, and ZEB1 binding sites on the promoters of Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5 was determined by Pscan Zambelli et al, 2009(). The resulted Z-scores were listed. "Max. M" suggested the maximum Z-score generated with SNAI2, TWIST1/2, and ZEB1 binding sites on one indicated promoter. "Average" suggested the average Z-score of all transcriptional factors tested in the Pscan software on one indicated promoter.",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "The expression of H1f1α, Snai2, Twist1/2, and Zeb1 was modulated with overexpression or sh-RNA-mediated knockdown via a retrovirus system during reprogramming with mES (B) The expression of Bmi1, Ctcf, Ezh2, Kdm2b, Wdr5 was determined on day 6 with qPCR and normalized against those in MEFs. The comparisons were performed between all groups and corresponding Flag groups.",
    "ncbi_link": "Flag: 
Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
H1f1α: 15251
Kdm2b: 30841
Snai2: 20583
Twist1: 22160
Wdr5: 140858
Zeb1: 21417"
  },
  {
    "caption": "The expression of H1f1α, Snai2, Twist1/2, and Zeb1 was modulated with overexpression or sh-RNA-mediated knockdown via a retrovirus system during reprogramming with 5C medium (C). The expression of Bmi1, Ctcf, Ezh2, Kdm2b, Wdr5 was determined on day 6 with qPCR and normalized against those in MEFs. The comparisons were performed between all groups and corresponding Flag groups.",
    "ncbi_link": "Flag: 
Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
H1f1α: 15251
Kdm2b: 30841
Snai2: 20583
Twist1: 22160
Wdr5: 140858
Zeb1: 21417"
  },
  {
    "caption": "pre-iPSCs were isolated during reprogramming with mES-Vc, mES or 5C medium. These pre-iPSCs were further cultured with a different medium (mES-Vc and mES medium) for seven days. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. The numbers of Oct4GFP+ colonies were determined on day 7 (E).",
    "ncbi_link": "Ctcf: 13018
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Reprogramming was also performed with mES-Vc or mES medium. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. AP+Oct4GFP- and AP+Oct4GFP+ colonies were counted on day 15 (G).",
    "ncbi_link": "Ctcf: 13018
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Reprogramming was also performed with mES-Vc or mES medium. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. In addition, energy metabolism was determined on day 6 with Seahorse instrument",
    "ncbi_link": "Ctcf: 13018
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Reprogramming was also performed with mES-Vc or mES medium. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. In addition, energy metabolism was determined on day 6 with Seahorse instrument",
    "ncbi_link": "Ctcf: 13018
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Reprogramming was also performed with mES-Vc or mES medium. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. Cell migration was determined by measuring the migration rate with live-cell imaging on day 6 (J).",
    "ncbi_link": "Ctcf: 13018
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Reprogramming was also performed with mES-Vc or mES medium. Additional factors (Hif1α, Hif1α overexpression; TGFβ, TGFβ1/2/3 1 ng/ml each; 3F, Ctcf, Kdm2b, and Wdr5 overexpression) were used simultaneously with mES medium. The expression of Bmi1, Ctcf, Ezh2, Kdm2b, or Wdr5 was determined on day 6 with qPCR (K).",
    "ncbi_link": "Bmi1: 12151
Ctcf: 13018
Ezh2: 14056
Hif1α: 15251
Kdm2b: 30841
Wdr5: 140858"
  },
  {
    "caption": "Expression of Hif1α was modulated via a retrovirus system or small-molecule compounds, oligomycin (1 µM) and 2-DG (5 mM), during reprogramming. The expression of mesenchymal markers (A)",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "Expression of Hif1α was modulated via a retrovirus system or small-molecule compounds, oligomycin (1 µM) and 2-DG (5 mM), during reprogramming. The expression of mesenchymal markers cell migration (B) was determined with qPCR and live-cell imaging, respectively, on day 6.",
    "ncbi_link": "Hif1α: 15251"
  },
  {
    "caption": "After sorting Oct4GFP+ cells out (5C-Oct4GFP+ and mES-Oct4GFP+ cells), the expression of markers of Xist (C)",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "The isolated 5C-Oct4GFP+ cells were cultured in naïve or primed medium for three days to generate 5C-Oct4GFP+ (naïve) and 5C-Oct4GFP+ (primed) cells. The expression of Xist (H)",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "(G) The average expression of both naïve and primed markers was calculated based on GSE100597. The top-2 cells from E4.5 epiblast and top-5 cells from E5.5 epiblast were selected. The expression of several naïve markers (Dppa3, Esrrb, Klf4, Klf5, Tbx3, and Zfp42) and several mesenchymal markers (Fgf5, Lef1, Nodal, and Pou3f1) in these selected cells were listed (upper part). The average expression of these genes in E3.5, 4.5, 5.5 and 6.5 epiblast were also listed (lower part). These results were all normalized against the average expression of these genes in all tested cells.",
    "ncbi_link": "Dppa3: 73708
Esrrb: 26380
Fgf5: 14176
Klf4: 16600
Klf5: 12224
Lef1: 16842
Nodal: 18119
Pou3f1: 18991
Tbx3: 21386
Zfp42: 22702"
  },
  {
    "caption": "(C) Benign breast epithelial MCF10A and breast carcinoma BT-474 cells were embedded in 3D collagen as single cells or as spheroids, respectively, and the growth was followed for 5 days. Light micrographs show filamentous actin (phalloidin) and nuclei (Hoechst) in representative cell colonies. Quantitative assessment of the nuclei counts per colony show the induced proliferation in MCF10A cells after ECHCD1 sgRNA knockout. At 72 hours, MCF10A mock versus ECHDC1_sgRNA_1 and ECHDC1_sgRNA_2 P < 0.05; at 96 hours mock versus ECHDC1_sgRNA_1, ECHDC1_sgRNA_2 and ECHDC1_sgRNA_3 P < 0.001; at 120 hours mock versus ECHDC1_sgRNA_1, ECHDC1_sgRNA_2 and ECHDC1_sgRNA_3 P < 0.0001. Nuclei count relative to mock 0 hours. Error bars indicate mean ± SEM; n ≥ 10 colonies. Statistical significance was assessed with one-way ANOVA with Tukey's multiple comparison test. Scale bar 50 µm.",
    "ncbi_link": "ECHCD1: 55862
ECHDC1: 55862"
  },
  {
    "caption": "(E) Measured metabolite levels of intermediates in propanoate metabolism in select breast cancer cell lines with or without the ECHDC1 rCCS status (n=7 in both groups). Boxes represent the interquartile range, whiskers represent the range of the values and solid line within the box correspond to the median value. Outlier points indicates values not included between the whiskers. Statistical significance was assessed with Wilcoxon test.",
    "ncbi_link": "ECHDC1: 55862"
  },
  {
    "caption": "(H) Survival analysis based on mRNA expression levels of DDX27 in patients with endometrial cancer in the TCGA dataset. Expression levels were divided into 2 classes, high (n=203) and low (n=322), based on mean expression level of DDX27 (logFPKM=18.27). Patients in the high class showed lower survival probability than those in the low class (P=.4.2×10-4; log-rank test).",
    "ncbi_link": "DDX27: 55661"
  },
  {
    "caption": "(I) mRNA expression levels of DDX27 in PTEN mutated (Mut, n=302) and PTEN wild type (WT, n=224) endometrial patient tumors in the TCGA dataset. Triangles correspond to the median value. P-value was calculated with Wilcoxon test.",
    "ncbi_link": "DDX27: 55661
PTEN: 5728"
  },
  {
    "caption": "Representative gene loci (TLR2 (top) and S100A7A/8/9/12 (bottom) H3K27ac peaks) comparing SC-naïve (blue) and SC-conv (red) monocytes. Red peaks reach higher values than blue peaks (representative examples of four samples for each condition).",
    "ncbi_link": "S100A7A: 338324
TLR2: 7097"
  },
  {
    "caption": "(B)  YTS KIR2DL1 cells were transfected with either N.S siRNA (blue curve) or with SHP-1  and Cbls siRNA (red curve). After 48 hours, cells were loaded with  calcium-sensitive Fluo-3-AM and analyzed for basal intracellular calcium levels for 1 min. The NK cells were then mixed with 721.221 Cw4 target cells at 37°C and monitoring of calcium levels was continued. The data shown are representative of three independent experiments.",
    "ncbi_link": "Cbls: 868///23624
Cw4: 3107
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(C)  YTS KIR2DL1 cells were incubated with either 721.221 Cw4 or Cw7 target cells for 2 hours and analyzed by flow cytometry to determine the expression of CD107a. Expression of  CD107a  was measured by mean fluorescence Intensity (MFI). Relative expression of CD107a  MFI was normalized to the mock-transfected sample following  Cw4 incubation. Data are means ± SEM of five independent experiments.(n=5). P values were calculated by One-sample t-tests and One way ANOVA following Tukey's post hoc analysis are indicated by asterisks *P < 0.05, ****P<0.0001 .",
    "ncbi_link": "Cw4: 3107
Cw7: 3107
KIR2DL1: 3802"
  },
  {
    "caption": "(E) Killing assay. YTS KIR2DL1 cells were mock-transfected or transfected with N.S siRNA or SHP-1 and Cbls siRNA. After 48 hours, cells were incubated with  [35S] Met-loaded 721.221 Cw4  or  Cw7 target cells. After 5 hours of co-culture, the supernatant was collected, and the radioactive  signal was measured. Data are means ± SEM of three independent experiments. P values were calculated by One-way ANOVA following Tukey's post hoc analysis and are indicated by asterisks *P < 0.05, **P < 0.01 .",
    "ncbi_link": "Cbls: 868///23624
Cw4: 3107
Cw7: 3107
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(A) NK92-NKp46low, NK92-NKp46high, YTS KIR2DL1,  K562 and  721.221 HLA-Cw4 cells were  stained with anti-NKp46  monoclonal antibody followed by staining  with Alexa568-Fluor goat anti-mouse IgG secondary antibody. Cells were then analyzed using flow cytometry. (B) NK92-NKp46low, NK92-NKp46+, YTS KIR2DL1, K562, and 721.221 HLA-Cw4 cells were incubated with 50 µg rhodamine-labeled NPs and analyzed using  flow cytometry to confirm the internalization of the coated NPs in a NKp46-specific manner. ",
    "ncbi_link": "HLA-Cw4: 3107
KIR2DL1: 3802
NKp46: 9437"
  },
  {
    "caption": "(C-F) (C) NK92-NKp46low, (D) NK92-NKp46high, (E) YTS KIR2DL1 and (F) K562  cells were incubated with 50 µg rhodamine-labeled NPs and analyzed using confocal microscopy. Upper panel shows wide field images. Lower panel shows single-cell images. The data shown are representative of three independent experiments.",
    "ncbi_link": "KIR2DL1: 3802
NKp46: 9437"
  },
  {
    "caption": "(A) YTS KIR2DL1 and  primary NK cells were incubated with NPs loaded with  Cbl-b, c-Cbl  and SHP-1 siRNA, or NPs loaded with 1500 pmol N.S siRNA. Following 48 hours of incubation, cells were lysed, and the membrane was  blotted with anti-Cbl-b, anti-c-Cbl or anti-SHP-1 antibodies. GAPDH served as loading control. Densitometric analysis of the bands was performed using ImageJ and normalized to the GAPDH densitometry values. Analysis by ImageJ densitometry  is summarized in the graph below. Data are means ± SEM of four independent experiments. (n=4). P values were calculated by One-sample t-tests and are indicated by asterisks. *P < 0.05, **P < 0.01.",
    "ncbi_link": "Cbl-b: 868
c-Cbl: 23624
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(B) YTS KIR2DL1 cells were incubated with SHP-1 and Cbls siRNAs-loaded NPs (red curve), with NS siRNA loaded NPs (green curve) or with empty NPs  (blue curve). After 48 hours, cells were loaded with calcium-sensitive Fluo-3-AM and analyzed for basal intracellular calcium levels for 1 min. The NK  cells were then mixed with 721.221 Cw4  target cells at 37°C, and monitoring of calcium levels was continued. The data shown are representative of three independent experiments.",
    "ncbi_link": "Cbls: 868///23624
Cw4: 3107
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(D)  YTS KIR2DL1 cells were treated with SHP-1 and Cbls  siRNAs-loaded NPs  or N.S siRNA-loaded  NPs. After 48 hours, cells were incubated with either  721.221 Cw4  or Cw7 target cells, the supernatant was then collected, and granzyme B levels were evaluated using ELISA sandwich  assay. The levels of granzyme B were quantified based on a standard curve. Data are means ± SEM of five independent experiments. (n=5). P values were calculated by One way ANOVA following Tukey's post hoc analysis, and are indicated by asterisks. **P < 0.01.",
    "ncbi_link": "Cbls: 868///23624
Cw4: 3107
Cw7: 3107
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(F) pNK cells were pretreated with either SHP-1 and Cbls siRNA-loaded NPs or N.S siRNA-loaded  NPs. After 48 hours, cells were incubated with either 721.221 Cw4 or Cw7 target cells for 2 hours and analyzed by flow cytometry to determine the expression of CD107a. Expression of CD107a was quantitated by mean fluorescence intensity (MFI). The data represent five independent experiments (n=5) Data are shown as mean ± SEM.) (n=5). P values were calculated by One-sample t-tests and One way ANOVA following Tukey's post hoc analysis, and are indicated by asterisks. *P≤0.05.",
    "ncbi_link": "Cbls: 868///23624
Cw4: 3107
Cw7: 3107
SHP-1: 5777"
  },
  {
    "caption": "(A)  YTS KIR2DL1 cells were incubated with SHP-1  and Cbls  siRNA-loaded NPs (red curve) or empty NPs (purple curve). After 48 hours, cells were loaded with  Fluo-3-AM and analyzed for intracellular calcium  levels for 20 min at 37°C.  YTS KIR2DL1 cells that were treated with PBS  served as a negative control (green curve). NK cells that were mixed with 721.221 Cw7  target cells served as a positive control (blue curve). Calcium levels were analyzed by spectrofluorometry. (n=3)",
    "ncbi_link": "Cbls: 868///23624
Cw7: 3107
KIR2DL1: 3802
SHP-1: 5777"
  },
  {
    "caption": "(B) Freshly isolated PBMCs were treated with SHP-1  and Cbls siRNA-loaded NPs, empty NPs, PBS as negative control or PHA as a positive control. Following incubation, supernatant from each sample was collected and the levels of  human  cytokines  TNF-α, IL-6, IL-10 and IFN-γ were determined using ELISA. The data represent four independent experiments (n=4). P values were calculated by One way ANOVA following Tukey's post hoc analysis, and are indicated by asterisks. *P≤0.008. Data are shown as mean ± SEM.",
    "ncbi_link": "Cbls: 868///23624
SHP-1: 5777"
  },
  {
    "caption": "(E) Following 24 hours after the last treatment, extracted cells from tumors of either SHP-1 and Cbls or N.S siRNA loaded NKp46-NPs treated mice  were analyzed by flow cytometry.  Expression of CD107a was measured by mean fluorescence Intensity (MFI). Relative expression of CD107a MFI was normalized to the sample treated with N.S siRNA loaded  NPs. The data represent three independent experiments. Data are shown as mean ± SEMn=3; P value was calculated by one sample t-test and is indicated within the graph P =0.009.",
    "ncbi_link": "Cbls: 868///23624
SHP-1: 5777"
  },
  {
    "caption": "(F)  Survival  analysis in mice treated with NK cells' gene silenced for SHP-1  and Cbls using siRNA-loaded  NPs  (n=18) or N.S siRNA-loaded NPs (n=18) as demonstrated by Kaplan-Meier survival curve. P values were calculated using the log-rank test and is indicated within the graph P =0.00009.",
    "ncbi_link": "Cbls: 868///23624
SHP-1: 5777"
  },
  {
    "caption": "d, STX17 knockdown COS7 cells expressing GFP-ATG14 and RFP-SEC61b; were immunostained for TOMM20. Error bars denote s.d.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "e, Immuoblot of subcellular fractions of STX17 knockdown (using two STX17 siRNAs, STX17-1 and STX17-2) HEK293 cells expressing GFP-DFCP1.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "b, Electron micrographs of STX17 knockdown cells. White arrows denote autolysosomes, black arrows denote autophagosome, white arrowheads mark isolation membranes.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "c, Immunogold electron micrographs of STX17 knockdown HeLa cells stained for GFP-LC3.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "d, GFP-ATG5 dots (arrows) in STX17 knockdown HeLa cells. e, Quantification of staining in d.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "f, Immunoblot of p62 in STX17 knockdown cells. Tubulin was used as a loading control.",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "g, Degradation of long-lived proteins in STX17 knockdown cells. St, starved; wor, wortmannin. All error bars denote s.d. Scale bars, 1 µm (a, b), 200 nm (c) and 5 µm (d).",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "C. Average dynamics of nucleoid separation and cell constriction for WT and the ΔmatP mutant strain. The cumulative distributions of the fraction of cells with two nucleoids (blue) and of the fraction of cells with a constriction degree above 0.15 (red) were plotted against cell age. Cell age was calculated according to the rank of each cell based on their cell length with the formula $\text{age}_{i}\left( F \right) = \ - \frac{ln(1 - \frac{F}{2})}{ln(2)}$, where F represents the fraction of cells with a cell length equal or below the length of cell i (Wold et al, 1994). D. Same plots as in C for three strains clustering in island 8 with the ΔmatP strain. The WT curves shown in C were plotted in gray for comparison. E. Same plots as in C for two island-8 strains, ΔycjV and ΔhslU, and the ΔhslV strain, which does not partition in island 8. ",
    "ncbi_link": "hslU: 948430
hslV: 948429
matP: 945570
ycjV: 945890"
  },
  {
    "caption": "B. The cumulative distribution of the proportion of constricting cells for the ftsA* mutant and its parent were plotted against cell age. We measured the degree of constriction of all cells using Oufti. For each strain, we had two independently acquired image sets (n = 496 and 1,168 cells for the WT replicates and n = 692 and 1,506 cells for the ftsA* replicates). The distributions of the degree of constriction were not significantly different among the four datasets at a threshold p-value of 0.01 using a Kruskal-Wallis multi-comparison test. Moreover, Bonferroni-corrected post-hoc pairwise tests did not allow a distinction between WT and ftsA* samples.",
    "ncbi_link": "ftsA: 944778"
  },
  {
    "caption": "C. Scatter plot of the CV of the cell length for the whole population versus the CV of the cell length for constricting cells only. The contour lines represent the 0.5, 075 and 0.95 probability envelopes of the 240 independent WT replicates. The gray color levels indicate the density of points in the vicinity of each strain. The ∆mraZ strain discussed in the text is highlighted in red.",
    "ncbi_link": "mraZ: 944810"
  },
  {
    "caption": "(a) Differential interference contrast micrographs of root epidermal cells incubated for 8 h with concanamycin A, in nutrient starvation conditions. Autophagic bodies accumulation in the vacuole is clearly visible in wild-type seedlings, absent in the atg5-1 mutant and restored in atg5-1 seedlings expressing ATG5-GFP. (b) Confocal microscopy. The ATG5-GFP fluorescence pattern in the atg5-1 background is identical to that observed in wild-type seedling, including ring-like structures. Scale bar, 15 μm.",
    "ncbi_link": "atg5: 831594"
  },
  {
    "caption": "(A) Phenotypes of wild type (Col), kup9 mutants (kup9-1 and kup9-2) and the kup9-1/ProKUP9:KUP9 complementation lines (COM1 and COM2). Seeds were germinated and grown on low-K+ (LK, 50 μM) or high-K+ (HK, 5 mM) medium for 7 d. Scale bar, 1 cm.",
    "ncbi_link": "kup9: 827740
KUP9: 827740"
  },
  {
    "caption": "(D) RT-qPCR analysis of KUP9 transcript levels in various materials. Data are means ± SE (n = 3, biological replicates; each replicate contains 120 individual plants).",
    "ncbi_link": "KUP9: 827740"
  },
  {
    "caption": "(A) Root meristem zones of wild type (Col), kup9 mutants (kup9-1 and kup9-2) and the kup9-1/ProKUP9:KUP9 complementation lines (COM1 and COM2). Seeds were germinated and grown on LK or HK medium for 7 d. The meristem zone lengths are marked with red lines. Scale bars, 50 μm.",
    "ncbi_link": "kup9: 827740
KUP9: 827740"
  },
  {
    "caption": "(A) to (F) Expression of KUP9 as determined in the ProKUP9:GUS line. GUS staining of 5-day-old seedling (A), root maturation zone (B), transverse section of maturation zone (C) and (D), primary root tip (E), and root apex (F). Ep, epidermis; Co, cortex; En, endodermis; Pe, pericyle; Xy, xylem; Ph, phloem. Scale bars, 5 mm in (A), 1 mm in (B), 10 μm in (C), 5 μm in (D), 1 mm in (E), and 20 μm in (F).",
    "ncbi_link": "GUS: 
KUP9: 827740"
  },
  {
    "caption": "(G) and (H) Expression of KUP9 protein as determined in the kup9-1/ProKUP9:KUP9-GFP transgenic plants. Green fluorescence shows the subcellular localization of KUP9-GFP. PI (propidium iodide) and ER tracker were used to indicate the positions of the plasma membrane (PM) and endoplasmic reticulum (ER) and are shown as red and cyan fluorescence, respectively. Scale bars for root tip, 10 μm in (G) and 5 μm in (H). Scale bars for EZ and MAZ, 20 μm.",
    "ncbi_link": "GFP: 
kup9: 827740
KUP9: 827740"
  },
  {
    "caption": "(A) QC cell observation in wild type and the kup9 mutants using the QC marker lines ProWOX5:GFP and ProQC25:GUS. Seeds were germinated on HK medium for 4 d, then the seedlings were transferred to LK or HK medium for the indicated times. Scale bars, 10 μm.",
    "ncbi_link": "GUS: 
QC25: 
kup9: 827740
WOX5: 820297"
  },
  {
    "caption": "(B) QC division rates of wild type and the kup9 mutants after LK treatment for 96 h. The statistical method is described in Materials and Methods. Data are means ± SE (n = 150, individual plants). Student's t-test (**P < 0.01) was used to analyze statistical significance, and "#" represents control.",
    "ncbi_link": "kup9: 827740"
  },
  {
    "caption": "(A) Auxin levels in root tips, as indicated by the ProDR5:GFP reporter line. Seeds were germinated on HK medium for 4 d, then the seedlings were transferred to LK or HK medium for the indicated times. Scale bar, 10 μm. (B) Quantification of GFP fluorescence in the QC cells shown in (A). Data are means ± SE (n = 20, individual plants). Student's t-test (**P < 0.01) was used to analyze statistical significance. ",
    "ncbi_link": "DR5: 
GFP: "
  },
  {
    "caption": "(C) QC cell observation using the QC marker line ProWOX5:GFP. Seeds were germinated on HK medium for 4 d, then the seedlings were transferred to LK or HK medium with or without NAA (100 nM) for 96 h. Scale bar, 10 μm.",
    "ncbi_link": "GFP: 
WOX5: 820297"
  },
  {
    "caption": "Phenotypes of the kup9-1/ProWOX5:AMI1 (A) transgenic lines. Seeds were germinated and grown on LK or HK medium with or without IAM for 7 d. Scale bars, 1 cm.",
    "ncbi_link": "AMI1: 837418
kup9: 827740
WOX5: 820297"
  },
  {
    "caption": "Phenotypes of the kup9-1/ProKUP9:AMI1 (C) transgenic lines. Seeds were germinated and grown on LK or HK medium with or without IAM for 7 d. Scale bars, 1 cm.",
    "ncbi_link": "AMI1: 837418
kup9: 827740
KUP9: 827740"
  },
  {
    "caption": "(B) 3H-IAA accumulation in the BY-2 cells expressing the indicated proteins. PIN4-GFP and KUP10-GFP were used as positive control and negative control, respectively. Data are means ± SE (n = 3, biological replicates; each replicate contains 3-4 mL suspension cells). Student's t-test (*P < 0.05, **P < 0.01) was used to analyze statistical significance, and "#" represent control.",
    "ncbi_link": "GFP: 
KUP10: 839997
PIN4: 814670"
  },
  {
    "caption": "(D) 3H-IAA accumulation in the oocytes expressing KUP9-GFP and PIN4 at the indicated times. PIN4 was used as a positive control. The oocytes were incubated in the bath solution containing 3H-IAA for the indicated times. Data are means ± SE (n = 6, biological replicates; each replicate contains 6 oocytes).",
    "ncbi_link": "GFP: 
KUP9: 827740
PIN4: 814670"
  },
  {
    "caption": "(F) K+ efflux activity of the oocytes expressing KUP9 and NRT1.5. The oocytes were not injected with IAA. The oocytes were incubated in K+-free bath solution for 6 h. Data are means ± SE (n = 3, biological replicates; each replicate contains 6 oocytes).",
    "ncbi_link": "KUP9: 827740
NRT1.5: 840139"
  },
  {
    "caption": "(C) to (E) The contents of free IAA (C), IA-Asp (D), and IA-Glu (E) in the root tips of wild type and the kup9-1 mutant. Data are means ± SE (n = 3, biological replicates; each replicate contains 1000-1200 individual plants). Student's t-test (*P < 0.05, **P < 0.01) was used to analyze statistical significance, and "#" represents control.",
    "ncbi_link": "kup9: 827740"
  },
  {
    "caption": "(F) Phenotype of the kup9-1/ProKUP9:PIN8 transgenic lines. Seeds were germinated and grown on LK or HK medium for 7 d. Scale bar, 1 cm.",
    "ncbi_link": "kup9: 827740
KUP9: 827740
PIN8: 831362"
  },
  {
    "caption": "(B) Interaction between PLD1 and ARL11/14 is stronger than with ARF1/6, RhoA. Flag-tagged PLD1 was co-expressed with HA-tagged GTP-bound mutants of small GTPases in HEK293A cells as indicated. PLD1 was immunoprecipitated with Flag beads, and the co-precipitated small GTPases were detected with an HA antibody. The result is a representative of three biologically independent experiments.",
    "ncbi_link": "Flag: 
GTP: 
HA: 
PLD1: 5337"
  },
  {
    "caption": "(C) ARL11/14 co-localize with PLD1. Flag-tagged PLD1 was co-expressed with HA-tagged GTP-bound mutants of small GTPases in HEK293A cells as indicated. After 24 h, cells were fixed with 4% paraformaldehyde, followed by incubation with anti-Flag and anti-HA primary antibodies. The Flag and HA-antibodies were detected by anti-mouse and anti-rabbit secondary antibodies, respectively. DAPI (blue) was used for DNA staining. Scale bars: 10 μm. The result is a representative of two biologically independent experiments.",
    "ncbi_link": "GTP: 
HA: "
  },
  {
    "caption": "(E) PLD1 preferentially binds to the GTP-form, not the GDP-form, of ARL11. Flag-tagged PLD1 was co-expressed with HA-tagged ARL11Q67L (GTP-form) or ARL11T26N (GDP-form) mutant in HEK293A cells. The result is a representative of two biologically independent experiments.",
    "ncbi_link": "Flag: 
HA: 
ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(F) The subcellular co-localization of ARL11 with PLD1 is GTP-dependent. HA-tagged GTP-bound ARL11Q67L, wild-type ARL11 or GDP-bound ARL11T26N was co-expressed with Flag-tagged PLD1. After 24 h, cells were fixed, followed by incubation with anti-Flag and anti-HA primary antibodies. DAPI (blue) was used for DNA staining. Scale bars: 10 μm. The result is a representative of three biologically independent experiments.",
    "ncbi_link": "Flag: 
ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(B) The loop region of PLD1 is required for the interaction between ARL11 and PLD1. Flag-tagged full-length or truncations of PLD1 was co-expressed with HA-tagged ARL11Q67L, PLD1 was immunoprecipitated with Flag beads, and ARL11 that associated with it was detected with an HA antibody. The result is a representative of two biologically independent experiments.",
    "ncbi_link": "Flag: 
HA: 
ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(C) Deletion of the loop region disrupts the PLD1 and ARL11 co-localization. Flag-tagged full-length or ∆Loop truncation of PLD1 was co-expressed with HA-tagged ARL11Q67L. After 24 h, cells were fixed with 4% paraformaldehyde, followed by incubation with anti-Flag and anti-HA primary antibodies. DAPI (blue) was used for DNA staining. Scale bars: 10 μm. The result is a representative of three biologically independent experiments. (D) Mander's overlap coefficient of (J). Mander's overlap coefficient calculated using JACoP plugin in ImageJ.",
    "ncbi_link": "Flag: 
HA: 
ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(B) ARL11 Knockout of THP-1 stable cell pools. ARL11 knockout THP-1 cell pools were generated by the CRISPR/Cas9 technology with three different guide RNAs. Cell lysates were immunoblotted with the indicated antibodies.",
    "ncbi_link": "CRISPR: 
ARL11: 115761
Cas9: 69900935"
  },
  {
    "caption": "(D) THP-1 cell pool stably expressing HA-tagged ARL11Q67L or ARL11T26N. Lysates were immunoblotted with indicated antibodies.",
    "ncbi_link": "HA: 
ARL11: 115761"
  },
  {
    "caption": "(E) ARL11Q67L, but not ARL11T26N, promotes phagocytosis of macrophages. Macrophages were differentiated from indicated THP1 cell pool, followed by incubated with green zymosan particles for 1 hour. Scale bars: 50 μm. The result is a representative of two biologically independent experiments.",
    "ncbi_link": "ARL11: 115761"
  },
  {
    "caption": "(G) PLD1 knockout efficiency and HA-tagged ARL11Q67L expression of THP-1 stable cell pools. Lysates were immunoblotted with indicated antibodies.",
    "ncbi_link": "HA: 
ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(H) PLD1 knockout blocks the ARL11Q67L-stimulated phagocytosis. Macrophages were differentiated from indicated THP1 cell groups and then incubated with green zymosan particles for 1.5 hours. Scale bars: 50 μm. The result is a representative of two biologically independent experiments. (I) PLD1 is required for ARL11 to stimulate phagocytosis. Data are quantification of panel (H).",
    "ncbi_link": "ARL11: 115761
PLD1: 5337"
  },
  {
    "caption": "(B) Interaction of PI4KB with ARL5A/5B is stronger than ARF1, RAB11A/11B, and RAB14. Flag-tagged PI4KB was co-expressed with HA-tagged GTP-bound mutant of GTPases in HEK293A cells as indicated. PI4KB was immunoprecipitated with Flag beads, and the co-precipitated GTPases were detected by HA Western.",
    "ncbi_link": "Flag: 
HA: 
PI4KB: 5298"
  },
  {
    "caption": "(C) PI4KB preferentially binds to the GTP-form of ARL5B. Flag-tagged PI4KB was co-expressed with HA-tagged ARL5BQ70L (GTP-form) or ARL5BT30N (GDP-form) mutant in HEK293A cells. Interaction was measured similar to panel B. The result is a representative of two biologically independent experiments.",
    "ncbi_link": "Flag: 
HA: 
ARL5B: 221079
PI4KB: 5298"
  },
  {
    "caption": "(D) The ARL5A colocalization with PI4KB is GTP-dependent. HA-tagged GTP-bound ARL5AQ70L, wild-type ARL5A or GDP-bound ARL5AT30N was co-expressed with Flag-tagged PI4KB. After 24 h, cells were fixed, followed by incubation with anti-Flag and anti-HA primary antibodies. DAPI (blue) was used for DNA staining. Scale bars: 10 μm. Shown is a representative of two biologically independent experiments. The left panel is the quantification of overlap coefficient. Mean± SD; n= 6 technically independent samples.",
    "ncbi_link": "HA: 
ARL5A: 26225"
  },
  {
    "caption": "(E) ARL5A/5B double knockout diminishes the colocalization of PI4KB and TGN46. Flag-tagged PI4KB was expressed in HEK293A wild-type or two ARL5A/5B double knockout clones as indicated. After 24 hours, cells were fixed, followed by incubation with anti-Flag and anti-TGN46 primary antibodies. DAPI (blue) was used for DNA staining. Scale bars: 5 μm. The result is a representative of two biologically independent experiments. The left panel is the quantification of overlap coefficient.",
    "ncbi_link": "ARL5A: 26225"
  },
  {
    "caption": "(G) The N1 region of PI4KB is required for the interaction with ARL5B. Flag-tagged full-length or truncations of PI4KB were co-expressed with HA-tagged ARL5BQ70L. PI4KB was immunoprecipitated with Flag beads, and the co-precipitated ARL5B was detected by HA Western. The result is a representative of three biologically independent experiments.",
    "ncbi_link": "Flag: 
HA: 
ARL5B: 221079
PI4KB: 5298"
  },
  {
    "caption": "(H) The N1 region of PI4KB is required for the co-localization of ARL5A/B and PI4P. P4Mx2-mEGFP was co-expressed with HA-tagged ARL5AQ70L in HEK293A wild-type or PI4KB knockout cells (clone#2-5). HEK293A cells were co-transfected with indicated constructs. After 24 h, cells were fixed with 4% paraformaldehyde, followed by incubation with anti-HA primary antibodies. DAPI (blue) was used for nuclei staining. Scale bars: 10 μm. The result is a representative of two biologically independent experiments. (I) Mander's overlap coefficient of (H).",
    "ncbi_link": "HA: 
ARL5A: 26225
PI4KB: 5298"
  },
  {
    "caption": "(B) ARL5A/5B recruitment to mitochondria induces PI4P accumulation at the mitochondria. Tom20-CFP-RFB and P4Mx2-mEGFP were co-expressed with RFP-FKBP vector or RFP-FKBP-ARL5A/5BQ70L constructs in HEK293A cells. Cell samples were treated with or without 100nM rapamycin for 1 hour. Scale bars: 10 μm. The dashed line box indicates the merged signal of PI4P with ARL5A/5B or Tom20. The result is a representative of two biologically independent experiments. (C) PI4KB knockout blocks the PI4P accumulation induced by mitochondria anchored ARL5A/5B. Tom20-CFP-RFB and P4Mx2-mEGFP were co-expressed with RFP-FKBP vector or RFP-FKBP-ARL5A/5BQ70L constructs in HEK293A PI4KB knockout cells (clone#2-5). Cell samples were treated with or without 100nM rapamycin for 1 hour before imaging. Scale bars: 10 μm. The dashed line box indicates the merged signal of PI4P with ARL5A/5B or Tom20. The result is a representative of two biologically independent experiments. (",
    "ncbi_link": "CFP: 
mEGFP: 
RFB: 
RFP: 
ARL5A: 26225
FKBP: 2280
PI4KB: 5298
Tom20: 9804"
  },
  {
    "caption": "(E) ARL5A/5B double knockout decreases protein secretion. Gaussia-luciferase was expressed in HEK293A wild-type or three ARL5A/5B double knockout clones as indicated. After 24 hours, the medium was replaced with the fresh medium. After 4 hours, medium was collected, and the secreted Gaussia-luciferase was detected by Western. Cells were also collected and probed with indicated antibodies",
    "ncbi_link": "ARL5A: 26225"
  },
  {
    "caption": "(H) PI4KB knockout blocks protein secretion stimulated by ARL5A/5BQ70L. Experiments were similar to panel (G). Gaussia-luciferase in culture medium was detected by Western and the cell lysate was immunoblotted with indicated antibodies.",
    "ncbi_link": "ARL5A: 26225
PI4KB: 5298"
  },
  {
    "caption": "A. HeLa, H1299 and A549 cells were infected with lentiviruses expressing control shRNA or lncRNA-MIF shRNA. Forty-eight hours after infection, cell lysates were subjected to Western blot analysis with anti-c-Myc antibody.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "C. Total RNA from the indicated cell lines was subjected to Northern blot analysis to determine the molecular size of lncRNA-MIF. Actin was also included as a positive control.",
    "ncbi_link": "Actin: 
lncRNA-MIF: "
  },
  {
    "caption": "D. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, cell lysates were analyzed by Western blotting with anti-c-Myc and anti-GAPDH antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "E. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, total RNA was extracted from these cells and subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "F. HeLa cells expressing either control RNA or lncRNA-MIF were treated with or without MG132 (20 μM) for 6 h. Cell lysates were analyzed by Western blot with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "G. HeLa cells expressing either control shRNA or lncRNA-MIF shRNA were treated with MG132 for 6 h. Cell lysates were analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "H. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS as indicated. Forty-eight hours after infection, cells were treated with cycloheximide (CHX, 50 μg/ml) for the indicated periods of time. Cell lysates were then analyzed by Western blotting to examine the c-Myc protein half-life. Protein band intensity were analyzed by ImageJ.I. Band intensity of c-Myc in Fig 1H was analyzed by ImageJ.",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "J. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3 as indicated. Forty-eight hours after infection, cells were treated with CHX for the indicated periods of time. Cell lysates were then analyzed by Western blotting to examine the half-life of c-Myc protein.K. Band intensity of c-Myc in Fig 1J was analyzed by ImageJ.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "A. P493-6 cells (human B cell lymphoma cell line) carrying a c-Myc tet-off system were treated with Doxycycline (1 μg/ml) for the indicated periods of time. Total RNA was subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test). Cell lysates were also analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "c-Myc: 4609"
  },
  {
    "caption": "B. HeLa, HCT116 and MCF10A cells were infected with lentiviruses expressing control shRNA or c-Myc shRNA. Forty-eight hours after infection, total RNA and cell lysates were analyzed by real-time RT-PCR and Western blotting, respectively. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "c-Myc: 4609"
  },
  {
    "caption": "E. HeLa cells were co-transfected with either Flag-c-Myc or control vector plus the indicated reporter constructs and Renilla luciferase plasmid. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Renilla luciferase: "
  },
  {
    "caption": "F. HeLa cells expressing control shRNA or c-Myc shRNA were co-transfected with the indicated reporter constructs and Renilla luciferase plasmid. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Renilla luciferase: 
c-Myc: 4609"
  },
  {
    "caption": "G. P493-6 cells were co-transfected with the indicated reporter constructs and Renilla luciferase plasmid. Twenty-four hours after trasfection, cells were treated with doxycycline for 0 hour and 12 hours respectively. Then reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "Renilla luciferase: "
  },
  {
    "caption": "A. Lysates from HeLa cells were incubated with in vitro synthesized biotin-labeled sense or antisense DNA probes against lncRNA-MIF for biotinpull-down assay, followed by Western blot analysis with the indicated antibodies. Lysates from HeLa cells were incubated with in vitro synthesized biotin-labeled lncRNA-MIF or biotin-labeled antisense RNA for biotinpull-down assay, followed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "B. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, cell lysates were analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "C. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, total RNA was subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "E. Lysates from HeLa cells were incubated with in vitro synthesized biotin-labeled sense or antisense DNA probes against lncRNA-MIF for biotinpull-down assay, followed by real-time RT-PCR analysis to examine miR-586 levels. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "F. Lysates from HeLa cells were incubated with in vitro synthesized biotin-labeled lncRNA-MIF and antisense RNA for biotinpull-down assay, followed by real-time RT-PCR analysis to examine miR-586 and miR-34a levels. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-34a: 407040
miR-586: 693171"
  },
  {
    "caption": "H. miR-586 or control mimics were transfected into HeLa cells together with the indicated pSICHECK2-based luciferase reporter construct. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
miR-586: 693171"
  },
  {
    "caption": "I. miR-586 or control inhibitors were transfected into HeLa cells together with the indicated pSICHECK2-based luciferase reporter construct. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
miR-586: 693171"
  },
  {
    "caption": "K. HeLa cells were subjected to cytoplasm or nucleus fractionation before each fraction was incubated with in vitro synthesized biotin-labeled sense or antisense DNA probes of lncRNA-MIF for biotinpull-down assay, followed by real-time RT-PCR analysis to examine miR-586 levels. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "B. miR-586 mimics or negative control mimics (NC mimics) were transfected into HeLa cells together with the indicated pSICHECK2-based luciferase reporter construct. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
miR-586: 693171"
  },
  {
    "caption": "C. miR-586 inhibitor or negative control inhibitor (NC inhibitor)was transfected into HeLa cells together with the indicated pSICHECK2-based luciferase reporter construct. Twenty-four hours after transfection, reporter activity was measured and plotted after normalizing with respect to Renilla luciferase activity. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "luciferase: 
Renilla luciferase: 
miR-586: 693171"
  },
  {
    "caption": "D. HeLa cells were transfected with miR-586 mimics or inhibitors as indicated. Forty-eight hours after transfection, cell lysates were analyzed by Western blotting.",
    "ncbi_link": "miR-586: 693171"
  },
  {
    "caption": "E. HeLa cells were transfected with miR-586 mimics or inhibitors as indicated. Forty-eight hours after transfection, total RNA was extracted and subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "miR-586: 693171"
  },
  {
    "caption": "F. The copy numbers of miR-586 and lncRNA-MIF transcript per cell in the indicated cells were quantified using a quantitative real-time RT-PCR assay. Data shown are mean ± SD (n = 3).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "G. HeLa cells were infected with lentiviruses expressing control shRNA or lncRNA-MIF shRNA. Forty-eight hours after infection, total RNA was subjected to real-time RT-PCR analysis. HeLa cells were infected with lentiviruses expressing lncRNA-MIF or control RNA. Forty-eight hours after infection, total RNA was analyzed by real-time RT-PCR. Data shown are mean ± SD (n = 3; *P < 0.05, **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "H. HeLa cells expressing lncRNA-MIF or control RNA were transfected with miR-586 mimics or NC mimics. Twenty-four hours after transfection, cell lysates were analyzed by Western blotting.",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "I. HeLa cells expressing lncRNA-MIF or control shRNA were transfected with miR-586 inhibitor or NC inhibitor. Twenty-four hours after transfection, cell lysates were analyzed by Western blotting.",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "K. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, lncRNA-MIF harboring nonsense mutation or miR-586 binding defective lncRNA-MIF. Forty-eight hours after transfection, cell lysates were analyzed by Western blotting.",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "A. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS. By Forty-eight hours infection, cells were treated with MG132 or DMSO (vehicle) for 6 h. Cell lysates were then analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "B. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS. Forty-eight hours after infection, total RNA was subjected to analyzing the levels of lncRNA-MIF and lncRNA-MIF-AS by real-time RT-PCR. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "C. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS. By 48 h infection, total RNA was subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "D. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3. By 48 h infection, cells were treated with MG132 or DMSO for 6 h. Cell lysates were then analyzed by Western blot analysis with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "E. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3. Forty-eight hours after infection, total RNA was subjected to real-time RT-PCR analysis. Data shown are mean ± SD (n = 3; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "A. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, acidification of the culture medium was evaluated by visually inspecting the color of the medium. Yellow medium indicates the presence of more lactate.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "B. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF, control shRNA, or lncRNA-MIF shRNA as indicated. Forty-eight hours after infection, cell lysates were analyzed by Western blotting with the indicated antibodies.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "C. HeLa cells expressing either lncRNA-MIF or control RNA were transfected with miR-586 mimics or negative control mimics (NC mimics) as indicated. Twenty-four hours after transfection, levels of lactate in the culture medium were measured and normalized to cell number. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "D. HeLa cells expressing either lncRNA-MIF or control RNA were transfected with miR-586 mimics or negative control mimics (NC mimics) as indicated. Twenty-four hours after transfection, intracellular glucose levels were measured and normalized based on protein concentration. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "E. HeLa cells expressing either lncRNA-MIF or control shRNA were transfected with miR-586 inhibitor or NC inhibitor as indicated. Twenty-four hours after transfection, levels of lactate in the culture medium were measured and normalized to cell number. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "F. HeLa cells expressing either lncRNA-MIF or control shRNA were transfected with miR-586 inhibitor or NC inhibitor as indicated. Twenty-four hours after transfection, intracellular glucose levels were measured and normalized based on protein concentration. Data shown are mean ± SD (n = 3; *P < 0.05, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "A. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS as indicated. Forty-eight hours after infection, growth curves were measured for the indicated periods of time. Data shown are mean ± SD (n = 3).",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "B. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3. Forty-eight hours after infection, growth curves were measured for the indicated periods of time. Data shown are mean ± SD (n = 3).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "C. HeLa cells were infected with lentiviruses expressing control RNA, lncRNA-MIF or lncRNA-MIF-AS as indicated. Forty-eight hours after infection, cells were stained with PI and analyzed by flow cytometry to identify phases of cell cycle.",
    "ncbi_link": "lncRNA-MIF: 
lncRNA-MIF-AS: "
  },
  {
    "caption": "D. HeLa cells were infected with lentiviruses expressing control shRNA, lncRNA-MIF shRNA-1, -2 or -3. Forty-eight hours after infection, cells were stained with PI and analyzed by flow cytometry to identify phases of cell cycle.",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "A. HeLa cells expressing either lncRNA-MIF or control RNA were transfected with miR-586 mimics or NC mimics as indicated. Colonies were stained with crystal violet and counted after 14 days incubation.",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "B. HeLa cells expressing either lncRNA-MIF shRNA or control shRNA were transfected with miR-586 inhibitors or NC inhibitors as indicated. Colonies were stained with crystal violet and counted after 14 days incubation.",
    "ncbi_link": "lncRNA-MIF: 
miR-586: 693171"
  },
  {
    "caption": "C. 2×106 HeLa cells expressing either lncRNA-MIF, lncRNA-MIF control RNA, lncRNA-MIF-shRNA or lncRNA-MIF control shRNA were individually injected subcutaneously into flanks of nude mice (n = 7 for each group). Representative photographs of xenografttumors in situ were taken 3 weeks after injection.D. Three weeks post graft, mice were euthanized, tumors were excised and weighed, and the mean tumor weight was plotted on the graph. Data shown are mean ± SD (n = 7; **P < 0.01, two-tailed t-test).",
    "ncbi_link": "lncRNA-MIF: "
  },
  {
    "caption": "B, C GOT2 can be acetylated. Flag‐tagged GOT2 was ectopically expressed in HEK293T cells treated with NAM (5 mM) and/or TSA (0.5 mM) for the indicated time period. Acetylation levels of Flag‐bead‐purified GOT2 were determined by Western blot analysis using a pan‐anti‐acetyllysine antibody (α‐Ac). IB and IP denote immunoblotting and immunoprecipitation, respectively. Relative GOT2 acetylation ratios were calculated after normalizing against Flag.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "D GOT2 acetylation enhances the interaction between ectopically expressed GOT2 and MDH2. Flag‐GOT2 and Myc‐MDH2 were co‐overexpressed in HEK293T cells treated without or with NAM (5 mM) for the indicated time period. The acetylation level of Flag‐bead‐purified GOT2 and the protein association between ectopic proteins of GOT2 and MDH2 were determined by Western blot analysis.",
    "ncbi_link": "GOT2: 2806
MDH2: 4191"
  },
  {
    "caption": "E Acetylation enhances the interaction between ectopically expressed GOT2 and endogenous MDH2. Flag‐GOT2 was co‐overexpressed in HEK293T cells treated without or with NAM (5 mM) for the indicated time period. The acetylation level of Flag‐GOT2 and its association with endogenous MDH2 were determined by Western blot analysis.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "F Acetylation enhances the interaction between ectopically expressed MDH2 and endogenous GOT2. Flag‐MDH2 was co‐overexpressed in HEK293T cells treated without or with NAM (5 mM) for the indicated time period. The protein association between Flag‐MDH2 and endogenous GOT2 was determined by Western blot analysis.",
    "ncbi_link": "MDH2: 4191"
  },
  {
    "caption": "H Mapping the major lysine residue(s) of acetylation in GOT2 whose acetylation can affect protein interaction between GOT2 and MDH2. Putative acetylated residues were divided into six groups according to their position in the structure of GOT2. Each group of putative acetylated lysine (K) sites was mutated to arginine (R), and the deacetylated mimic K‐to‐R mutants were examined for their protein association with ectopically expressed Myc‐MDH2 by Western blot analysis.",
    "ncbi_link": "GOT2: 2806
MDH2: 4191"
  },
  {
    "caption": "I GOT2 coupled with MDH2 shows a high level of K159 acetylation. Flag‐GOT2 was overexpressed in HEK293T cells without or with co‐overexpression of Myc‐MDH2. These transfected cells were treated with NAM (5 mM) for 5 h. Double immunoprecipitation was performed to obtain the Flag‐GOT2 from the Myc‐MDH2 immunoprecipitates (Ppt, supposed to be GOT2 bound with MDH2). The remaining supernatants (Sup, supposed to be GOT2 not bound with MDH2) were also harvested and precipitated by Flag antibody to test the K159 acetylation level of Flag‐GOT2 by Western blot analysis.",
    "ncbi_link": "GOT2: 2806
MDH2: 4191"
  },
  {
    "caption": "J The 3KQ/R mutations do not change GOT2 enzyme activity. Wild‐type and 3K mutant GOT2 proteins were overexpressed and purified from E. coli, and the enzyme activity of GOT2 was determined as described in \"\". Shown are average values with standard deviation (SD) of triplicated experiments. n.s. = not significant for the indicated comparison.",
    "ncbi_link": "GOT2: 14719///2806"
  },
  {
    "caption": "A, B Glucose and glutamine increase GOT2 K159 acetylation and GOT2-MDH2 association in HEK293T cells. Flag‐GOT2 and Myc‐MDH2 were overexpressed in cells treated with increased concentrations of glucose (A) or glutamine (B) for 6 h. GOT2 proteins were purified by Flag beads, and the K159 acetylation level of GOT2 and its protein association with Myc‐MDH2 were determined by Western blot analysis.",
    "ncbi_link": "GOT2: 2806
MDH2: 4191"
  },
  {
    "caption": "C, D Glucose and glutamine increase GOT2 K159 acetylation in Panc‐1 cells. Flag‐GOT2 was overexpressed in cells treated with different concentrations of glucose (C) and glutamine (D) for 4 h. GOT2proteins were purified by Flag beads, and the K159 acetylation level of GOT2 was determined by Western blot analysis. Relative GOT2 K159 acetylation levels were normalized against Flagprotein levels.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "E, F Quantification of the percentage of K159‐acetylated endogenous GOT2 in Panc‐1 cells. Recombinant fully K159‐acetylated GOT2 was loaded onto the same gel, together with endogenous GOT2 from Panc‐1 cells treated without or with glucose (12 mM) (E) or glutamine (2 mM) (F) for 4 h. GOT2 protein and K159 acetylation were detected by Western blot. The percentages of K159 acetylation in GOT2 were calculated after normalizing against GOT2 protein levels.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "G, H 3K mutant GOT2 displays negligible response in changing protein association with MDH2 after glucose or glutamine treatment. Panc‐1 cells with GOT2 knockdown and re‐expression of wild‐type or 3K mutant GOT2 were treated with glucose (G) or glutamine (H) at the indicated concentrations for 4 h. The protein association between Flag‐tagged wild‐type or 3K mutant GOT2 and endogenous MDH2 was determined by Western blot analysis.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "A GOT2 interacts with SIRT3, but not SIRT4 and SIRT5. Flag‐tagged GOT2 was ectopically expressed in HEK293T cells together with the individual HA‐tagged SIRT as indicated. Proteins were purified by IP with Flag beads, following Western blot to detect SIRTs with an HA antibody.",
    "ncbi_link": "GOT2: 2806
SIRT3: 23410
SIRT4: 23409
SIRT5: 23408"
  },
  {
    "caption": "B Endogenous proteins of GOT2 and SIRT3 interact with each other. SIRT3 protein in HEK293T cells was purified by IP with an anti‐SIRT3 antibody, following Western blot to detect GOT2 with an anti‐GOT2 antibody.",
    "ncbi_link": "SIRT3: 23410"
  },
  {
    "caption": "C GOT2 deacetylation is dependent on SIRT3 catalytic activity. Flag‐tagged GOT2 was ectopically expressed in HEK293T cells together with HA‐tagged wild‐type SIRT3 and a catalytically inactive mutant, SIRT3 H248Y. GOT2 proteins were purified by Flag beads, following Western blot to detect GOT2 K159 acetylation.",
    "ncbi_link": "GOT2: 2806
SIRT3: 23410"
  },
  {
    "caption": "D SIRT3 impairs the protein interaction between GOT2 and MDH2. HEK293T cells were transfected with the plasmids as indicated. GOT2 proteins were purified by Flag beads, and their protein interaction with Myc‐MDH2 was determined by Western blot.",
    "ncbi_link": "MDH2: 4191
SIRT3: 23410"
  },
  {
    "caption": "E Knockdown of SIRT3 increases GOT2 K159 acetylation and enhances GOT2-MDH2 association. HEK293T cells with or without transient SIRT3 knockdown were transfected with the plasmids as indicated. GOT2 proteins were purified by Flag beads, and the K159 acetylation level of GOT2 and its protein association with endogenous MDH2 were determined by Western blot analysis.",
    "ncbi_link": "GOT2: 14719///2806
SIRT3: 23410"
  },
  {
    "caption": "F, G Knockdown of SIRT3 diminishes the effect of glucose or glutamine on changing GOT2 K159 acetylation. Flag‐tagged GOT2 was ectopically expressed in HEK293T cells without or with transient SIRT3 knockdown. These cells were treated with different concentrations of glucose (F) and glutamine (G) as indicated. GOT2 proteins were purified by Flag beads, and the K159 acetylation level of GOT2 was determined by Western blot analysis.",
    "ncbi_link": "GOT2: 2806
SIRT3: 23410"
  },
  {
    "caption": "B, C GOT2 3K acetylation promotes the net transfer of cytosolic NADH into mitochondria. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, the NADH level in the cytosol (B) and mitochondrion (C) was determined in cell extracts as described in .",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "D GOT2 3K acetylation regulates mitochondrial NADH/NAD+ redox in the cell. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, the ratio of NADH/NAD+ in the mitochondria of cells was measured as described in .",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "E GOT2 3K acetylation promotes ATP production. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, ATP production was determined in cell extracts as described in .",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "F GOT2 3K acetylation promotes NADPH production. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, the ratio of NADPH/NADP+ was determined in cell extracts as described in .",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "G GOT2 3K acetylation promotes GSH production. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, the GSH/GSSG ratio was determined in cell extracts as described in .",
    "ncbi_link": "GOT2: 14719///2806"
  },
  {
    "caption": "H GOT2 3K acetylation suppresses cellular ROS levels. In Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins, ROS was determined as described in in cells under non‐stressed condition or exposed to menadione (50 μM for 30 min).",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "I GOT2 3K acetylation protects cells from oxidative damage. Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins were treated with increasing concentrations of menadione for 3 h as indicated, and cell viability was determined by counting the remaining adherent cells.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "J, K Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins were seeded in a 6‐well plate, and the cells were maintained under the condition of low glucose (0.5 mM, J) or high glucose (12 mM, K). Culture medium was refreshed every day, and cell numbers were counted every 1-2 days over a period of 7 days.",
    "ncbi_link": "GOT2: 2806"
  },
  {
    "caption": "A-C GOT2 3K acetylation promotes xenograft tumorgrowth. Panc‐1 stable cells with GOT2 knockdown and re‐expressing the indicated proteins (2 × 106cells) were injected subcutaneously into the flanks of nude mice. The tumor volume was carefully monitored over the indicated time period (A). At 8 weeks after injection, tumors from six mice were extracted, photographed, and weighted (B, C).",
    "ncbi_link": "GOT2: 14719"
  },
  {
    "caption": "D GOT2 3K acetylation promotes tumor cellproliferation. Tumor sections from xenografts were prepared for IHC staining, and the PCNA‐stained tumor sections were analyzed by quantifying the PCNA‐positive area.",
    "ncbi_link": "GOT2: 14719"
  },
  {
    "caption": "(B) Ectopically-expressing Sc-CCM1 rescues the respiration defect of Sc+Sb-chr7. Spot assays for the wild-type S. cerevisiae (Sc) and the chromosome 7 replacement stain (Sc+Sb-chr7) carrying an empty plasmid (+ vector) or the plasmid with the S. cerevisiae CCM1 gene (+ Sc-CCM1).",
    "ncbi_link": "CCM1: 853053"
  },
  {
    "caption": "(C) Sb-CCM1 incompatibility could only be rescued in the presence of S. bayanus mtDNA. The native CCM1 ORF in S. cerevisiae was replaced by either Sb-CCM1 (Sc+Sb-CCM1) or Sc-CCM1 (Sc+Sc-CCM1, as a control) coding regions. Crossing the Sc+Sb-CCM1 strain with the mtDNA-less Sb-ρ⁰ strain (Sc+Sb-CCM1 x Sb-ρ⁰) could not rescue the growth defect.",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(D) CCM1 incompatibility is symmetric between S. cerevisiae and S. bayanus. The CCM1 ORF in S. bayanus was replaced by either Sc-CCM1 (Sb+Sc-CCM1) or Sb-CCM1 (Sb+Sb-CCM1, as a control) coding regions. Only the Sb+Sc-CCM1 strain exhibited respiration defects and the defect could not be rescued even when a whole set of S. cerevisiae chromosomes were provided (Sb+Sc-CCM1 x Sc-ρ⁰).",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(E) CCM1 incompatibility probably occurred during the divergence between S. bayanus and the common ancestor of S. cerevisiae, S. paradoxus, S. mikatae and S. kudriavzevii. The endogenous CCM1 in S. cerevisiae was replaced with its orthologous alleles from other Saccharomyces sensu stricto yeasts. Only the strain carrying S. bayanus CCM1 displayed growth defects on glycerol-containing plates.",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(B) The level of 15S rRNA is reduced in Sc+Sb-CCM1 cells. RNA isolated from Sc+Sb-CCM1 (labeled as Sb) or Sc+Sc-CCM1 (labeled as Sc) cells was hybridized with gene-specific probes using Northern blots.",
    "ncbi_link": "CCM1: 
15S: 9164990
CCM1: 853053"
  },
  {
    "caption": "(C) Sb-Ccm1 interacts weakly with S. cerevisiae 15S rRNA. The level of Ccm1-bound 15S rRNA was measured using quantitative PCR analysis following mitochondrial RNA immunoprecipitation of S. cerevisiae cells expressing Sc-CCM1-13Myc or Sb-CCM1-13Myc. Data was normalized to the control group without the Myc tag to obtain the relative fold enrichment. Graph was plotted using data from three independent repeats for each strain and p value was calculated by unpaired, two-sided student t-test. Error bars indicate S.D. ***, p value < 0.001.",
    "ncbi_link": "15S: 9164990"
  },
  {
    "caption": "(D) Overexpressing Sb-CCM1 rescues the respiration defect of Sc+Sb-CCM1 cells. Cell cultures were serially-diluted and spotted onto YPD (glucose) or YPG (glycerol) plates. The plates were then incubated at 28°C until colonies were easily observed.",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(E) The steady-state level of mtDNA-encoded proteins is reduced in Sc+Sb-CCM1 cells. Immunoblotting for the mitochondrial proteins in Sc+Sb-CCM1 (labeled as Sb) or Sc+Sc-CCM1 (labeled as Sc) cells. Cox1, Cox2 and Cox3 are mtDNA-encoded complex IV subunits. Tom20 is a nucleus-encoded mitochondrial protein.",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(A) Tetrad analysis reveals that the respiration defect of Sc+Sb-CCM1 cells can be rescued by mutations in mitochondrial or nuclear genomes. The suppressor clones were crossed with the Sc+Sb-CCM1-ρ⁰ strain and the tetrads from the cross were analyzed. A non-Mendelian 4:0 segregation pattern for improved respiration is expected if the suppressor mutation is in mtDNA (left panel). Otherwise, a 2:2 segregation pattern would be observed if the rescue effect involved a single nuclear mutation (right panel).",
    "ncbi_link": "CCM1: 
CCM1: 853053"
  },
  {
    "caption": "(A) Reconstituted Sb-CCM1 mutants can rescue the incompatibility of Sb-CCM1. Among 94 suppressor clones, 20 of them carry mutations in the Sb-CCM1 gene. These mutants were reconstructed in Sc+Sb-CCM1 cells to test their function. Superscripts next to Sb-CCM1 indicate the respective amino acid substitutions and numbers in parentheses indicate the number of independent clones in our suppressor screen. Sc, wild-type S. cerevisiae.",
    "ncbi_link": "CCM1: "
  },
  {
    "caption": "(C) The 400th residue plays a determinant role in the S. cerevisiae-S. bayanus incompatibility. Both Sb-CCM1E375Q and Sb-CCM1D400N mutants relieved the incompatibility in S. cerevisiae, but only Sb-CCM1D400N caused respiration defects in S. bayanus. The Sb-CCM1E375Q mutant was selected as a control in this experiment since it was a charged-to-polar substitution similar to Sb-CCM1D400N and also appeared three times in our screen. Sb, wild-type S. bayanus.",
    "ncbi_link": "CCM1: "
  },
  {
    "caption": "(A) 15S rRNA levels are increased in the suppressor clones. Total RNA was isolated from the replacement strains (Sc+Sc-CCM1 and Sc+Sb-CCM1), two nuclear suppressor strains (Sc+Sb-CCM1D400N and Sc+Sb-CCM1E375Q) and one mitochondrial suppressor strain and then subjected to quantitative PCR analyses. Relative mRNA abundance was calculated by normalizing the 15S rRNA level to the ATP6 mRNA level. Graph was plotted using data from five independent repeats for each strain and p values were calculated by unpaired, two-sided student t-test. Error bars indicate S.D. ***, p value < 0.001. **, p value < 0.01. Asterisks in black, comparing Sc+Sc-CCM1 with others. Asterisks in gray, comparing Sc+Sb-CCM1 with others.",
    "ncbi_link": "ATP6: 
CCM1: 
15S: 9164990
CCM1: 853053"
  },
  {
    "caption": "H. Mass chromatograms of the nucleosides,  Um (Q1/Q3 = 259.1/113.1), Cm  (Q1/Q3 = 258.1/112.1), and G (Q1/Q3 = 284.1/152.2) of HctRNAGly(GCC), HctRNAGly(CCC), HctRNAGly(UCC), and HctRNAPros isolated from WT and hTrmt13  KO cells. Um, 2′-O-methyluridine,  Cm, 2′-O-methylcytidine. Q1/Q3: the mass of the precursor  ion and the mass of the product  ion. These endogenous  tRNAs were purified separately from total cellular RNAs using sequence-specific probes.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "I. Quantification of the Um/G and Cm/G ratios in endogenous tRNAs isolated from WT and hTrmt13 KO cells. Quantification was performed by comparison with the standard curve obtained from pure nucleoside standards running in the same batch. Statistical analysis was performed using t-tests. Error bars represent mean ± SD for three independent experiments.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "A. De novo protein synthesis measured by puromycin incorporation in shSCR,  hTrmt13 knockdown cells (sh-1 and sh-2), and sh-1 with stable expression of wild type  hTrmt13 (sh-1+hTrmt13) or enzymatically-inactive hTrmt13 (sh-1+E463A). Puromycin-labeled proteins were detected by immunoblotting. Representative images (left) and statistical analysis (right) are shown. Knockdown and overexpression efficiency of hTrmt13 in MDA-MB-231 verified by Western blots. Data information: Statistical analysis was performed using t-tests, and error bars represent mean ± SD for three independent experiments.",
    "ncbi_link": "hTrmt13: 54482"
  },
  {
    "caption": "C. The in vivo aminoacylation level of hTrmt13 substrate  tRNAs assayed by Northern blot. The samples were also deacylated (DA) by incubating with alkaline buffer (pH 9.0) to obtain fully uncharged  tRNA control.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "I. The  binding profiles of hTrmt13, H3K4me3, H3K27Ac, and other transcription factors (MYC, E2F1, TP53, FOSL1, EZH2, FOXM1) from ChIP-seq  and ATAC-seq on representative target genes  TGFB1, MEF2A, and PKN2. hTrmt13 track were average across 2 biological replicates.",
    "ncbi_link": "MEF2A: 4205
PKN2: 5586
TGFB1: 7040"
  },
  {
    "caption": "B. Transwell migration assays in MDA-MB-231 cells. Control with siRNA scramble (NC), treated with siRNA against hTrmt13 (si-1, si-2) and stably expressing wild-type hTrmt13  (si-1+WT) or enzymatic inactive hTrmt13 mutant (si-1+E463A). Representative images (left panel) and statistical analysis (middle panel) are shown. Data information: for each group, five different fields were chosen and counted using a microscope with 20-fold magnification. Statistical analysis was performed using t-tests. Error bars represent mean ± SD for four independent experiments.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "C. Transwell migration assays in HCC38 cells infected with scrambled siRNA (NC) or siRNA against hTrmt13 (si-1, si-2). Data information: for each group, five different fields were chosen and counted using a microscope with 20-fold magnification. Statistical analysis was performed using t-tests. Error bars represent mean ± SD for three independent experiments.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "E. Volcano plot of differential expressed genes analysis results for  RNA-seq data comparing hTrmt13 knockdown MDA-MB-231 cells (N=2) to control cells (N=2), the dots for significant regulated genes (FDR corrected p-value < 0.05) were colored red, the dots and labels of interesting genes with oncogenic implications have been colored in blue or red.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "B.  Interaction  of FLAG-hTrmt13 with endogenous FOSL1, E2F1, and  USF1. Whole-cell lysates from MDA-MB-231 cells stably expressing FLAG-hTrmt13 were prepared and  immunoprecipitation was performed with anti-FLAG followed by immunoblotting with antibodies against indicated proteins.",
    "ncbi_link": "FLAG: 
Trmt13: 54482"
  },
  {
    "caption": "F. ChIP-qPCR analysis of the selected promoters was performed using antibodies against indicated proteins in control and hTrmt13 knockdown MDA-MB-231 cells. Results are represented as fold change over control IgG. Statistical analysis was performed using t-tests. Error bars indicate mean ± SD for three independent experiments.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "C. The binding shift assays of hTrmt13, USF1, and their mixture for synthesized DNA from the TGFB1  promoter. In the reaction system, 10 ng/μL DNA was used, and 1 μM hTrmt13 or 1 μM USF1  or a mixture (0.5 μM hTrmt13 + 0.5 μM USF1) was applied. D. The binding shift assays of hTrmt13 for HctRNAGly(GCC) with the presence of various concentrations of USF1. In the reaction system, 0.3 μM HctRNAGly(GCC) and 0.5 μM hTrmt13 were used, and a varied amount of USF1 (0, 0.5, 1, 2, 3, 4 μM) were used. E. The binding shift assays  of hTrmt13 (0.5 μM), or USF1 (0.5 μM) or the hTrmt13-USF1 complex (0.5 μM) for both tRNA (0.1 μM) and  DNA (15 ng/μL) in the same reaction.",
    "ncbi_link": "TGFB1: 7040"
  },
  {
    "caption": "A. Volcano plot of differential expressed  genes analysis results for RNA-seq data on TCGA comparing hTrmt13 expression low group patients (first quartile) versus high group patients (fourth quartile). Significant differentially expressed genes (FDR corrected p-value < 0.05) were colored by red, interesting genes with oncogenic implications are labelled in blue. Pseudo values 1e-15 were added to FDR correlated p-value for better visualization.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "F. Kaplan-Meier survival analysis of Kaplan-Meier plotter (http://kmplot.com/analysis/) for the relationship between the  relapse-free survival (RFS) or overall survival time (OS) of  breast cancer patients (BRCA, n=349 (low)/205 (high)),  liver cancer patients (LIHC, n=270 (low)/100 (high)), patients with kidney renal clear cell carcinoma (KRIC, n=156 (low)/374 (high)), and  patients with kidney renal papillary cell carcinoma (KIRP, n=208 (low)/79 (high)) and their expression of hTrmt13.",
    "ncbi_link": "Trmt13: 54482"
  },
  {
    "caption": "B Staining of nucleic acids after fixation. The propidium iodide signal in fibroblasts was significantly higher for samples fixed with glyoxal pH 4 (N = 6-8). To test whether the fixed nucleic acids were still available for specific detection, we performed FISH for GAPDH in cultured neurons, using a standard protocol provided by the company Affymetrix. The fluorescence signal of the samples fixed with glyoxal (pH 4) was significantly higher than for PFA-fixed samples (N = 5-6). Scale bar = 10 µm, * p < 0.05, ** p < 0.01",
    "ncbi_link": "GAPDH: 24383"
  },
  {
    "caption": "Left: NIH-3T3 cells expressing sgCtrl, sgP5CS-1 or sgP5CS-2 were treated with TGFβ or mock for 48h, and proline abundance was measured by GC-MS. Values are relative to mock-treated sgCtrl expressing cells. Right: western blot of NIH-3T3 cells expressing sgCtrl, sgP5CS-1 or sgP5CS-2.",
    "ncbi_link": "P5CS: 56454"
  },
  {
    "caption": "Western blot of NIH-3T3 cells expressing sgCtrl or sgP5CS-2 and treated with TGFβ or mock for 48h in the presence or absence of 0.15 mM proline.",
    "ncbi_link": "P5CS: 56454"
  },
  {
    "caption": "Collagen abundance in ECM produced by NIH-3T3 cells expressing sgCtrl or sgP5CS-2 grown in the presence or absence of TGFβ and 0.15 mM proline, measured by picrosirius red staining and normalized to the packed cell volume of cells grown on a parallel plate under identical conditions. Values are relative to mock-treated sgCtrl expressing cells.",
    "ncbi_link": "P5CS: 56454"
  },
  {
    "caption": "Proline abundance in NIH-3T3 cells expressing empty vector or HA-P5CS cDNA, measured by GC-MS. Values are relative to mock-treated empty vector expressing cells.",
    "ncbi_link": "P5CS: 
HA: "
  },
  {
    "caption": "Western blot of NIH-3T3 cells expressing empty vector or HA-P5CS cDNA.",
    "ncbi_link": "HA: 
P5CS: 5832"
  },
  {
    "caption": "Collagen abundance in ECM produced by NIH-3T3 cells expressing empty vector or HA-P5CS cDNA, measured by picrosirius red staining and normalized to the packed cell volume of cells grown on a parallel plate under identical conditions. Values are relative to mock-treated",
    "ncbi_link": "HA: 
P5CS: 5832"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of P5CS: (i) lung tissue from mice with pulmonary fibrosis induced by bleomycin (Bleo) treatment compared to saline treatment (GSE112827);",
    "ncbi_link": "P5CS: 56454"
  },
  {
    "caption": "Pearson correlation of P5CS mRNA level and forced vital capacity (FVC) before bronchodilator (pre-BD) as percentage of what was predicted for each patient, from clinical data of GSE32537.",
    "ncbi_link": "P5CS: 5832"
  },
  {
    "caption": "Tracing of [U-13C] L-glutamine ([U-13C] Gln) into indicated metabolites. NIH-3T3 cells expressing sgCtrl, sgSmad4-1 or sgSmad4-2 were treated with TGFβ or mock for 48h and the medium was replaced (including all treatments) with DMEM without L-glutamine and supplemented with [U-13C] Gln for the last 8h. Metabolites were measured by GC-MS.",
    "ncbi_link": "Smad4: 17128"
  },
  {
    "caption": "Left: western blot of NIH-3T3 cells expressing empty vector, mitoTPNOX or mitoLbNOX. MitoTPNOX or mitoLbNOX expression is detected by probing for their FLAG-tag. Right: NIH-3T3 cells expressing empty vector, mitoTPNOX or mitoLbNOX were treated with TGFβ or mock for 48h and proline abundance was measured by GC-MS. Values are normalized to mock-treated empty vector expressing cells.",
    "ncbi_link": "mitoLbNOX: 
mitoTPNOX: "
  },
  {
    "caption": "NIH-3T3 cells expressing sgCtrl, sgSmad4-1 or sgSmad4-2 were treated with TGFβ or mock for 6h, and ROS levels were measured by flow cytometry for CM-H2DCFDA after incubation with CM-H2DCFDA for the last 30 min of the treatment. Values are normalized to mock-treated sgCtrl expressing cells.",
    "ncbi_link": "Smad4: 17128"
  },
  {
    "caption": "Western blot of NIH-3T3 cells expressing sgCtrl, sgSmad4-1 or sgSmad4-2 and treated with TGFβ or mock for 6h in the presence of 0.5% FBS.",
    "ncbi_link": "Smad4: 17128"
  },
  {
    "caption": "NIH-3T3 cells expressing mito-Grx1-roGFP2 or cyto-Grx1-roGFP2 were treated with TGFβ or mock for 6h or with 100 µM H2O2 as a control. Emission was measured with a 520/10nm filter after excitation with 405nm and 488nm lasers using flow cytometry. Oxidized roGFP2 gains excitability at 405nm and loses excitability at 488nm. Oxidation status is expressed as percentage of maximal oxidation which was determined by treating cells with 5 mM H2O2 for 5 min before harvest.",
    "ncbi_link": "roGFP2: 
Grx1: 2745"
  },
  {
    "caption": "NIH-3T3 cells expressing sgCtrl or sgP5CS-2 were treated with TGFβ or mock for 48h in the presence of 0.15 mM proline. ROS levels were measured by flow cytometry for CM-H2DCFDA after incubation with CM-H2DCFDA for the last 30 min of the treatment.",
    "ncbi_link": "P5CS: 56454"
  },
  {
    "caption": "Left: NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2 were treated with TGFβ or mock for 6h, and ROS levels were measured by flow cytometry for CM-H2DCFDA after incubation with CM-H2DCFDA for the last 30 min of the treatment. Values are relative to mock-treated sgCtrl expressing cells. Right: western blot of NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2.",
    "ncbi_link": "Slc25a1: 13358"
  },
  {
    "caption": "NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2 were treated with TGFβ or mock for 48h and proline abundance was measured by GC-MS. Values are relative to mock-treated sgCtrl expressing cells.",
    "ncbi_link": "Slc25a1: 13358"
  },
  {
    "caption": "Western blot of NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2 and treated with TGFβ or mock for 48h.",
    "ncbi_link": "Slc25a1: 13358"
  },
  {
    "caption": "Collagen abundance in ECM produced by NIH-3T3 cells expressing sgCtrl, sgSlc25a1-1 or sgSlc25a1-2 grown in the presence or absence of TGFβ, measured by picrosirius red staining and normalized to the packed cell volume of cells grown on a parallel plate under identical conditions. Values are relative to mock-treated sgCtrl expressing cells.",
    "ncbi_link": "Slc25a1: 13358"
  },
  {
    "caption": "NIH-3T3 cells expressing empty vector or Slc25a1 cDNA were treated with TGFβ or mock for 6h, and ROS levels were measured by flow cytometry for CM-H2DCFDA after incubation with CM-H2DCFDA for the last 30 min of the treatment. Values are relative to mock-treated empty vector expressing cells.",
    "ncbi_link": "Slc25a1: 6576"
  },
  {
    "caption": "NIH-3T3 cells expressing empty vector or Slc25a1 cDNA were treated with TGFβ or mock for 48h, and proline abundance was measured by GC-MS. Values are relative to mock-treated empty vector expressing cells.",
    "ncbi_link": "Slc25a1: 6576"
  },
  {
    "caption": "Western blot of NIH-3T3 cells expressing empty vector or Slc25a1 cDNA and treated with TGFβ or mock for 48h.",
    "ncbi_link": "Slc25a1: 6576"
  },
  {
    "caption": "Collagen abundance in ECM produced by NIH-3T3 cells expressing empty vector or Slc25a1 cDNA grown in the presence or absence of TGFβ, measured by picrosirius red staining and normalized to the packed cell volume of cells grown on a parallel plate under identical conditions. Values are relative to mock-treated empty vector expressing cells.",
    "ncbi_link": "Slc25a1: 6576"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of Slc25a1, as described in Figure 3: (j) lung tissue from mice with pulmonary fibrosis induced by bleomycin (Bleo) treatment compared to saline treatment (GSE112827);",
    "ncbi_link": "Slc25a1: 13358"
  },
  {
    "caption": "Analysis of the indicated gene expression datasets for mRNA levels of Slc25a1, as described in Figure 3: two datasets (GSE110147, GSE32537) from lungs of patients with idiopathic pulmonary fibrosis (IPF) compared to normal controls (Ctrl). AU, arbitrary units. The number of patients per group is indicated.",
    "ncbi_link": "Slc25a1: 6576"
  },
  {
    "caption": "Pearson correlation of Slc25a1 and P5CS mRNA levels in IPF patients from GSE32537. IPF patients from GSE32537 were assigned into P5CSlow/SLC25A1high and P5CShigh/SLC25A1low groups based on the expression level of P5CS and SLC25A1. "High" represents patients with P5CS or SLC25A1 expression values being above the 75% percentile of the respective gene expression; "low" represents patients with expression values being below the 25% percentile of gene expression. The forced vital capacity (FVC) before bronchodilator (pre-BD) as percentage of what was predicted for each patient was compared between the groups.",
    "ncbi_link": "P5CS: 5832
Slc25a1: 6576
SLC25A1: 6576"
  },
  {
    "caption": "D. Brain lysate as in (A) was incubated with GST or GST-nCLCb proteins with boundaries as indicated. Specifically bound proteins were detected by Western blot with antibody against CLCs.",
    "ncbi_link": "CLCb: 116561"
  },
  {
    "caption": "Ai-x. Lateral view of the adult fly head. Scale bar = 100 μm.i. longGMR,UAS-Rac1W/TM6B, Hu, Tb causes a mild rough eye phenotype with fused (arrows) and disorganized but still separated ommatidia (arrowheads).ii/iii. Rac1 overexpression with KD of dlrrk (UAS-dlrrk-RNAi (v22139 or v22140)/longGMR-GAL4, UAS-Rac1W), results in smaller eyes where most ommatidia are fused.iv/v. Rac1 overexpression with KD of Clc (UAS-Clc-RNAi (v22318 or v106632)/+;longGMR-GAL4,UAS-Rac1W/+), results in smaller eyes with some ommatidia fused.vi. Rac1 overexpression with KD of the inwardly rectifying potassium channel 3 (irk3), a non-relevant RNAi control (UAS-irk3-RNAi(v101174)/+; longGMR-GAL4,UAS-Rac1W/+), has no effect.vii/viii. KD of dlrrk with GMR-GAL4/+; UAS-dlrrk-RNAi(v22139 or 22140)/+, respectively as control have no effect on eye morphology.ix/x. KD of Clc with GMR-GAL4/UAS-Clc-RNAi (v22318 or v106632), respectively as control have no effect on eye morphology.",
    "ncbi_link": "Hu: 40835
Clc: 40221
irk3: 35131
dlrrk: 42447
Rac1: 38146
Tb: 252803"
  },
  {
    "caption": "Bi-ii. Lateral view of the adult fly head. Scale bar: 100 μm.i. Rac1 overexpression with removing one copy of dlrrk (dlrrke03680/longGMR-GAL4,UAS-Rac1W), results in smaller eyes where most ommatidia are fused together.ii. Removing one copy of dlrrke03680 in GMR-GAL4 background, as control has no effect on eye morphology (GMR-GAL4/+;dlrrke03680/+).",
    "ncbi_link": "dlrrk: 42447
Rac1: 38146"
  },
  {
    "caption": "Ci-viii. Lateral view of the adult fly head. Scale bar: 100 μm.i. longGMR,UAS-Rac1W/TM6B, Hu, Tb causes a mild rough eye phenotype with fused and disorganized but still separated ommatidia (as explained in Ai).ii. Rac1 co-expression with dlrrk-WT using UAS-dlrrk-WT/+;longGMR-GAL4,UAS-Rac1W/+, results in rescued eye morphology.iii. Rac1 co-expression with Clc using UAS-GFP-Clc/+;longGMR-GAL4,UAS-Rac1W/+, results in rescued eye morphology.iv. Rac1 co-expression with dlrrk-WT-3KD using UAS-dlrrk-3KD/+;longGMR-GAL4,UAS-Rac1W/+, results in rescued eye morphology.v. A wild-type eye of the longGMR-GAL4 promoter as a control.vi-viii. Overexpression of dlrrk-WT, dlrrk-3KD, or Clc alone with GMR-GAL4 as control, have no effect on eye morphology.",
    "ncbi_link": "Hu: 40835
Clc: 40221
dlrrk: 42447
Rac1: 38146
Tb: 252803"
  },
  {
    "caption": "(B) Immunoblotting of whole cell extracts obtained from parental and RAP80-/- clones in the RPE-1 hTERT p53-/- Cas9, RPE-1 hTERT p53-/- BRCA1-/- Cas9, U2OS, U2OS-2-6-3 and U2OS Flp-In/TREx cell lines with RAP80 antibodies. Tubulin is used as loading control. Representative of at least two independent immunoblots. See Figure EV1 for further details on the gene editing strategy used to knockout RAP80.",
    "ncbi_link": "RAP80: 29086
BRCA1: 672
Cas9: 59376643
p53: 7157"
  },
  {
    "caption": "(C, D) The indicated parental and RAP80-/- cell lines were processed for immunofluorescence 1 h post-irradiation (10 Gy) and stained with antibodies against ABRAXAS1 and γH2AX. Shown in (C) is the percentage of cells with > 5 ABRAXAS1 foci that colocalize with γH2AX. A minimum of 100 cells per replicate were analyzed and the bars represent the mean ± S.D. (n=3 biological replicates). Representative micrographs of RPE1-hTERT p53-/- Cas9 wild type (WT) and RAP90-/- cells are shown in (D).",
    "ncbi_link": "RAP90: 
RAP80: 29086
Cas9: 59376643
p53: 7157"
  },
  {
    "caption": "(G) RPE-1 hTERT p53-/- Cas9 parental (WT) and RAP80-/- cells were untreated (t=0 h) or irradiated with a 10 Gy dose. Samples were collected at the indicated time points, processed for immunofluorescence and stained with antibodies against BRCA1 and γH2AX. Shown is the percentage of cells with > 5 BRCA1 foci. A minimum of 100 cells per replicate were analyzed and the datapoints represent the mean ± S.D. (n=3 biological replicates). All scale bars are 5 μm.",
    "ncbi_link": "RAP80: 29086
Cas9: 59376643
p53: 7157"
  },
  {
    "caption": "(A, B) U2OS Flp-In/T-Rex parental (WT) and RAP80-/- cells were transfected with siRNA pools targeting BRCA1, RNF8, RNF168 or BARD1 or with a non-targeting control siRNA (CTRL). 48 h post-transfection cells were irradiated (2 Gy) and processed for immunofluorescence 1 h post-IR treatment using antibodies against BRCA1 and γH2AX. Quantitation of the percentage of cells with > 5 BRCA1 foci that colocalize with γH2AX is shown in (A). A minimum of 100 cells per replicate were analyzed and the bars represent the mean ± S.D. (n=3 biological replicates). Representative micrographs are shown in (B).",
    "ncbi_link": "RAP80: 29086
BARD1: 580
BRCA1: 672
RNF168: 165918
RNF8: 9025"
  },
  {
    "caption": "(C, D) Parental (WT) RPE1-hTERT p53-/- Cas9, RNF8-/-, and RNF168-/- cells were treated with either a non-targeting siRNA pool (CTRL) or a pool targeting RAP80. 48 h post-transfection cells were irradiated (2 Gy) and processed for immunofluorescence 1 h post-IR treatment using antibodies against BRCA1 and γH2AX. Quantitation of the percentage of cells with > 10 BRCA1 foci that colocalize with γH2AX is shown in (C). A minimum of 100 cells per replicate were analyzed and the bars represent the mean ± S.D. (n=3 biological replicates). Representative micrographs are shown in (D). All scale bars are 5 μm.",
    "ncbi_link": "RAP80: 29086
Cas9: 59376643
RNF168: 165918
RNF8: 9025
p53: 7157"
  },
  {
    "caption": "(A, B) U2OS Flp-In/T-REx cells with integrated transgenes encoding GFP-BRCA1BRCT or -BRCA1BRCT S1655A were transfected with non-targeting siRNA (CTRL) or siRNA targeting RAP80 or BRCA1. Following doxycycline treatment to induce transgene expression (5 μg/mL, 24 h), cells were irradiated (10 Gy) and processed for immunofluorescence 1 h post-IR for GFP and antibodies against RAP80 and γH2AX. Shown in (A) is the quantitation of a minimum of 100 cells per replicate where the bars represent the mean ± S.D (n=4). Representative micrographs are shown in (B).",
    "ncbi_link": "GFP: 
RAP80: 29086
BRCA1: 672"
  },
  {
    "caption": "(C, D) U2OS Flp-In/T-REx cells stably integrated with the indicated transgenes were treated with doxycycline (5 μg/mL, 36 h) to induce protein expression and transfected with an siRNA targeting BRCA1 and also either non-targeting siRNA (CTRL) or siRNAs targeting RAP80. 1 h post-irradiation (10 Gy) cells were processed for immunofluorescence using GFP (to detect the BRCA1 fusions) and antibodies against γH2AX. Shown in (C) is the quantitation of a minimum of 100 cells per replicate where the bars represent the mean ± S.D (n=3 biological replicates). Representative micrographs are shown in (D). All scale bars are 5 μm.",
    "ncbi_link": "RAP80: 29086
BRCA1: 672"
  },
  {
    "caption": "(A, B) U2OS 2-6-3 parental (WT) or RAP80-/- cell lines were transfected with siRNAs targeting BRCA1 followed by nucleofection of the indicated GFP fusion proteins. 48 h post-nucleofection, mCherry-LacR-FokI expression was induced for 5 h prior to being processed for fluorescence microscopy for GFP and mCherry. Shown in (A) is the quantitation of GFP fluorescence at the mCherry focus where the bars represent the mean ± S.D (n= 50, 50, 40, 40, 40, 40, 20, 20, 30, 30 cells analyzed from 3 biological replicates). Representative micrographs for the BRCA1 and BRCA1-I26A conditions are shown in (B). Additional micrographs for the other conditions are in Figure EV2C.",
    "ncbi_link": "RAP80: 29086
BRCA1: 672"
  },
  {
    "caption": "(C) RPE-1 hTERT p53-/- BRCA1-/- Cas9 cells (WT) or their isogenic RAP80-/- counterparts expressing the indicated GFP fusion proteins were processed 1 h post-irradiation (10 Gy) for immunofluorescence using GFP and antibodies against BRCA1 and γH2AX. A minimum of 100 cells per replicate were analyzed and the bars represent the mean ± S.D (n=3 biological replicates). Representative micrographs are shown in Figure EV3B. (D) RPE-1 hTERT p53-/- BRCA1-/- Cas9 cells or their isogenic RAP80-/- counterparts expressing the indicated GFP fusion proteins were processed 1 h post-irradiation (10 Gy) for immunofluorescence using GFP and antibodies against RAD51 and γH2AX. A minimum of 100 cells per replicate were analyzed and the bars represent the mean ± S.D (n=3 biological replicates). Representative micrographs are shown in Figure EV3C. Scale bar is 5 μm in (B).",
    "ncbi_link": "RAP80: 29086
BRCA1: 672
Cas9: 59376643
p53: 7157"
  },
  {
    "caption": " Immunoblot of media and lysate collected from HEK293T cells overexpressing ERdj3WT or ERdj3KDEL. Fresh media was conditioned on cells for 24 h prior to harvest. ",
    "ncbi_link": "ERdj3: 51726"
  },
  {
    "caption": " qPCR analysis of ERdj3 mRNA in HEK293T cells treated with or without thapsigargin (Tg; 6 h, 100 nM). Error bars represent the mean ± 95% confidence interval as calculated in DataAssist 2.0 (n = 3). ",
    "ncbi_link": "ERdj3: 51726"
  },
  {
    "caption": "  Representative immunoblot of lysates and media collected from HEK293T-Rex cells stably expressing non-silencing (NS) or ERdj3 shRNA. Cells were treated with the indicated concentration of Tg in fresh media for 16 h. Quantification of the fold increase of ERdj3 in lysates and media collected from HEK293T-Rex cells treated with the indicated concentration of Tg in fresh media for 16 h as in Figure 1C. *indicates a pvalue < 0.05; (n = 3).  ",
    "ncbi_link": "ERdj3: 51726"
  },
  {
    "caption": "Immunoblot in lysates and media collected from HEK293DAX cells following 16 h of activation of XBP1s [by 1 g/mL dox] and/or ATF6 [by 10 M TMP], as indicated (Shoulders et al, 2013). Immunoblots of the ATF6 target protein BiP (reactive with the KDEL antibody) and the XBP1s target Sec24D confirm the small molecule activation of these transcription factors.",
    "ncbi_link": "ATF6: 22926
XBP1: 7494"
  },
  {
    "caption": "  Representative autoradiogram of [35S]-labeled ERdj3 immunopurified from lysates and media collected from HEK293DAX cells following preactivation of XBP1s [by 1 g/mL dox] and/or ATF6 [by 10 M TMP] (Shoulders et al, 2013). The experimental protocol is shown above. Quantification of relative amounts of [35S]-labeled ERdj3 in media at 8 h collected from cells treated as shown in Figure 2B (n=3). The media [35S]-labeled ERdj3 was measured by densitometry and is normalized to the amount of media [35S]-labeled ERdj3 at 8 h from vehicle-treated cells. Error bars represent standard error from biological replicates (n = 3). * indicates p-value < 0.05; ** indicates p-value < 0.01; *** indicates p-value < 0.001 as compared to the vehicle-treated condition. Quantification of the fraction ERdj3 secreted from autoradiograms as shown in Figure 2B. The fraction of ERdj3 secreted was calculated by normalizing the recovered [35S]-labeled ERdj3 signal in the media at t = 4 or 8 h to the total amount of [35S]-labeled ERdj3 signal in the media and lysates at t = 0 h. Error bars represent standard error from biological replicates (n = 3). * indicates p-value < 0.05; ** indicates p-value < 0.01 as compared to the vehicle-treated condition. Quantification of the fraction ERdj3 remaining from autoradiograms as shown in Figure 2B. The fraction of ERdj3 remaining was calculated by normalizing the sum of the recovered [35S]-labeled ERdj3 signal in the media and in the lysates at t = 4 or 8 h to the total amount of [35S]-labeled ERdj3 signal in the media and lysates at t = 0 h. Error bars represent standard error from biological replicates (n = 3). * indicates p-value < 0.05; ** indicates p-value < 0.01 as compared to the vehicle-treated condition.  ",
    "ncbi_link": "ATF6: 22926
XBP1: 7494"
  },
  {
    "caption": "Immunoblot of conditioned media collected from HEK293T cells transiently transfected with ERdj3WT or ERdj3H53Q and incubated with an affinity resin consisting of native (N) or guanidinium hydrochloride (GdnHCl)-denatured (D) RNAse A covalently coupled to sepharose resin. Resin was incubated with media for 2 h at ambient temperature, followed by washing and elution in Laemmli's reducing buffer.",
    "ncbi_link": "ERdj3: 51726"
  },
  {
    "caption": "  Representative images under 136X magnification of PK1 cells incubated with control conditioned media collected from HEK293T-Rex or conditioned media prepared from HEK293T-Rex cells overexpressing ERdj3WT in the presence or absence of TPrP (600 ng/mL), as described in Figure 4A. Arrows indicate representative cells containing vacuoles. Insets show 544X magnification of a typical region of the image. Quantification of vacuole formation from images as shown in Figure 4B. Equal area images comprising ~1200 cells per well were counted for each sample. Counting of cells and of cells with identifiable vacuoles was done using the Fiji image processing package (Schindelin et al, 2012). *** indicates a p-value < 0.001 (n = 3).  ",
    "ncbi_link": "ERdj3: 51726"
  },
  {
    "caption": "Immunoblot of M2 anti-FLAG immunopurifications from the conditioned media collected from HEK293T cells overexpressing FTTTRWT, FTTTRA25T, and/or ERdj3WT either as a co-incubation or co-expression experiment as shown in Figure 5A. Beads were washed in RIPA buffer prior to elution. Media inputs (1:400) are shown as a control.",
    "ncbi_link": "ERdj3: 51726
TTR: 7276"
  },
  {
    "caption": "Immunoblot of M2 anti-FLAG immunopurifications from media collected from HEK293T cells overexpressing ERdj3WT and FTTTR variants as indicated. Media inputs (1:400) are shown as a control.",
    "ncbi_link": "TTR: 7276"
  },
  {
    "caption": "Immunoblot of 6E10 anti-APP immunopurifications from the conditioned media of CHO cells or CHO-derived APP751-expressing (7WD10) cells overexpressing ERdj3WT as indicated. Cells were replated together as indicated 24 h after transfection at equal stoichiometry, and media conditioned for 36 h. In this case, ERdj3 transfected CHO cells replated with mock-transfected 7WD10 cells serves as the co-incubation condition, while mock-transfected CHO cells replated with ERdj3-transfected 7WD10 cells comprise the co-expression condition. Media inputs (1:150) are shown as a control.",
    "ncbi_link": "APP: 351
ERdj3: 51726"
  },
  {
    "caption": "  Representative immunoblot of M2 anti-FLAG immunopurification of media conditioned for 24 h on HEK293DAX cells co-overexpressing FTTTRA25T and ERdj3WT or ERdj3H53Q. Media contained vehicle or trimethoprim (TMP, 10 M, 16 h; activates ATF6), as indicated. Media inputs (1:400) are shown as a control. Lysates from these cells are also shown to confirm the increase of the ATF6 target proteins BiP and GRP94 in cells following TMP-dependent activation of ATF6. Bar graph depicting quantification of the change in the amount of ERdj3 co-immunoprecipitating with TTRA25T following activation of ATF6, as in Figure 6A. The ERdj3/TTR ratio is normalized to the ratio in the absence of ATF6 activation. *indicates a p-value < 0.05; n = 3.  ",
    "ncbi_link": "ATF6: 22926
ERdj3: 51726"
  },
  {
    "caption": " Representative immunoblot of M2 anti-FLAG immunopurification of media conditioned for 24 h on HEK293T cells co-overexpressing FTTTRA25T, ERdj3WT, ERdj3H53Q, and/or BiP, as indicated. Media inputs (1:400) are shown as a control. Lysates from these cells are also shown to confirm the increase of BiP afforded by overexpression. ",
    "ncbi_link": "ERdj3: 51726
BiP: 3309"
  },
  {
    "caption": "Quantification of immunoblots of M2 anti-FLAG immunopurification of media collected from cells co-overexpressing either ERdj3WT or ERdj3H53Q, FTTTRA25T, and BiP, as in Figure 6C. The ERdj3/TTR ratio is normalized to the ratio in the absence of BiP overexpression. **indicates a p-value < 0.01; n = 5.",
    "ncbi_link": "ERdj3: 51726
BiP: 3309"
  },
  {
    "caption": "Immunoblot of 6E10 anti-APP immunopurifications from the conditioned media of CHO cells or CHO-derived APP751-expressing (7WD10) cells overexpressing ERdj3WT, ERdj3H53Q, and BiP as indicated. Media inputs (1:100) are shown as a control. Lysates from these cells are also shown to confirm the increase of BiP afforded by overexpression.",
    "ncbi_link": "APP: 351
ERdj3: 51726
BiP: 3309"
  },
  {
    "caption": "B. Comparison of ΔPrP expression levels. Representative immunoblot is shown for detection of (3F4)MoPrP and ΔPrPs in transiently transfected N2a cells using mAb 3F4. ΔPrPs are similar in expression level glycosylation appearance, except for Δ159-167 which has an extra fragment larger than the diglycoform (lane 7, arrow).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "C. ΔPrPs are not converted into PK-resistant PrP in prion-infected cells. 22L-ScN2a cells were transiently transfected with (3F4)MoPrP, Δ159 or Δ159-175, and cell lysates digested with PK or not. Immunoblot was done using mAb 3F4.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": ". D. Pilot study for dominant-negative inhibition (DNI) of Δ159 and Δ159-175. DNI was assessed by co-transfecting 22L-ScN2a cells with (3F4)MoPrP and Δ159 or Δ159-175, respectively, and testing for PK-resistant (3F4)MoPrP. Left panel shows representative immunoblot (mAb 3F4) and right panel the statistical analysis of quantified PK-res levels of a triplicate experiment. Empty pcDNA3.1 plasmid was used as control for co-transfection in lane 1. The error bars indicate standard deviation. *, p<0.05.",
    "ncbi_link": "pcDNA3.1: 
PrP: 19122"
  },
  {
    "caption": "A. N-linked glycans of ΔPrPs are not complex-type. Immunoblot comparing EndoH- and non-digested lysates of ΔPrP159 and Δ159-175 transfected cells. Left panel was probed with mAb 3F4 mAb, detecting transiently expressed ΔPrPs. On the right panel, the membrane was re-probed with mAb 4H11, detecting total PrP. Arrowheads depict deglycosylated ΔPrPs.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "C. ΔPrPs are mainly distributed in intracellular compartments rather than on the cell surface. Confocal microscopy images of N2a cells transiently transfected with (3F4)MoPrP, Δ159 or Δ159-175, either permeabilized (right) or non-permeabilized (left) with 0.2% TX100 after fixation. Cells were immuno-labeled with mAb 3F4. (3F4)MoPrP-expressing cells show bright immunopositivity on the cell surface, whereas ΔPrPs are not observed on the cell surface. Also intracellular staining differs strongly between (3F4)MoPrP and ΔPrP expressing cells Scale bars, 25 µm.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A. ΔPrPs are insoluble in detergent solution. Immunoblots showing partition of Δ159 and Δ159-175 in supernatant (Sup) and pellet fraction after ultracentrifugation of lysates supplemented with 4% sarcosyl. Upper panel is mAb 3F4, lower panel is membrane re-probed with mAb 4H11 detecting also endogenous wild-type PrP besides ΔPrPs. The majority of ΔPrPs is found in the insoluble fraction in both infected and non-infected cells (upper panel, lanes 3, 4, 7 and 8). Wild-type PrP almost completely partitions into the soluble fraction (Sup) in non-infected N2a cells with present conditions. PrP in pellet fractions of non-infected N2a cells is from ΔPrPs as can be seen from the banding pattern (Lane 7 and 8, square bracket). PrP in lanes 3 and 4 (lower panel) is PrP27-30.",
    "ncbi_link": "PrP: 19122
PrP: P04925///19122"
  },
  {
    "caption": "B. ΔPrPs are moderately resistant to chymotrypsin digestion. Immunoblots showing chymotrypsin-resistant fragments of Δ159 and Δ159-175 from transiently transfected N2a cell lysates digested with indicated concentrations of chymotrypsin (Chy). Note that full-length diglycoform of ΔPrP still remains at 8 µg/ml Chy (lanes 5 and 10, upper panel, closed arrowhead), whereas that of endogenous wild-type PrP is completely digested (lanes 5 and 10, lower panel, open arrowhead) and only small amounts of truncated fragments remained (curly bracket). Other smaller fragments in lane 5 and 10 (square-brackets) represent ΔPrPs.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A. ΔPrPs are substantially soluble in detergent without GdnHCl denaturation. Immunoblots probed with mAbs 3F4 (left) or 4H11 (right, membrane re-probed) showing ΔPrPs and endogenous PrP in detergent and aqueous phases of TX114 lysates prepared from N2a cells transfected with Δ159 or Δ159-175. Det denotes detergent phase, Aq aqueous phase.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B. ΔPrPs are highly hydrophobic after denaturation with GdnHCl. Representative immunoblot of TX114-treated lysates after denaturation with 3 M GdnHCl and developed with mAb 3F4 showing Δ159 and Δ159-175 almost exclusively in detergent phase (lanes 1-4). PIPLC treatment (+, even lanes) was done after denaturation with GdnHCl or not (−, uneven lanes). PIPLC treatment did not significantly influence ΔPrP partitioning under these conditions.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "C. Hydrophobicity of ΔPrPs combined with sensitivity to PIPLC digestion. After further diluting out GdnHCl by phase-separation and removal of the aqueous phase containing GdnHCl, PIPLC was able to digest ΔPrPs. Left two panels (upper mAb 3F4, lower 4H11) are shorter expositions, right panels longer expositions to show also difference in PrP levels in the detergent phase. Under these conditions a substantial reduction of ΔPrPs in the detergent phase was achieved by PIPLC digestion (e.g. upper-left panel, lanes 1, 3 vs. 2, 4). Migration of ΔPrPs in the aqueous phase of PIPLC-digested samples was slightly slower than that of PIPLC-undigested samples (−) (upper-right panel, lane 9 vs. 10).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A. Degradation of ΔPrPs by lysosomal and proteasomal systems. (Left) N2a cells transiently transfected with Δ159 or Δ159-175 were treated for 7 hours with inhibitors either for lysosomal degradation (bafilomycin A1, Baf, 120 nM), autophagy (3-methyladenine, 3MA, 10 mM), or the proteasome (MG132, 10 µM) and cell lysates analyzed in immunoblot for expression of Δ159 and Δ159-175 (mAb 3F4). Square bracket and bracket denote diglycoforms and nonglycoforms of ΔPrPs, respectively. An increment in diglycoforms is observed in Baf- and 3MA-treated cells, whereas in MG132-treated cells also the non-glycoforms are increased. (Right) A graph showing quantification of all PrP bands by densitometric analysis. Data from 3 independent (one in duplicate) experiments for Δ159 and 2 independent (one in duplicate) for Δ159-175 were statistically analyzed for mean and standard deviation (error bars).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B. ΔPrPs can be localized in LAMP1-immunopositive vesicles. Immunofluorescence analysis shows distribution of ΔPrP (mAb 3F4) and LAMP1 in cells with or without 6M GdnHCl antigen-retrieval treatment. N2a cells transfected with ΔPrP159 were fixed, permeabilized and incubated without (upper panel) or with 6M GdnHCl (lower panel). With GndHCl treatment ΔPrP is diffusely distributed (arrowheads) and co-localizes poorly with LAMP1. After GdnHCl treatment (lower panel), bright 3F4-immunopositive puncta (arrows) are observed which partly co-localize with LAMP1-positive structures (merge). Scale bars, 10 µm.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A. DNI efficiencies of ΔPrPs are inversely correlated to deletion size. Representative immunoblot showing PK-resistant PrPSc moiety of (3F4)MoPrP co-expressed with indicated ΔPrPs in 22L-ScN2a cells. Quantitative analysis is shown below as scheme. Relative PrPSc levels were calculated as proportion of PK-resistant (3F4)MoPrP co-transfected with each ΔPrP to that of co-transfected with empty vector control in the same experiment. Data from 4 (for Δ159-165, Δ159-167 and Δ159-167(169) only 3) independent experiments were statistically analyzed for mean and standard deviation (error bars).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B. DNI of ΔPrP with a deletion in the C-terminal part of H1∼H2. Δ171-175 (see Fig. 7A) was transiently expressed in N2a cells (left panel) and DNI efficiency evaluated in 22L-ScN2a cells (right panel) (mAb 3F4). Despite the much shorter deletion size, Δ171-175 exerted only inefficient DNI, similar to Δ159-175 (right panel).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": ". B. Δ31-160 variants are expressed at comparable levels and have EndoH-sensitive and -resistant N-glycans. Immunoblot comparing EndoH-digested and non-digested samples from N2a cells transiently transfected with Δ31-160 variants, probed with anti-PrP mAb C16-S raised against the C-terminal portion of H3. Non-Tf, samples prepared from N2a cells without transfection. Arrowhead denotes deglycosylated Δ159 (lane 11), bracket deglycosylated fragments, square bracket EndoH-resistant fragments. Asterisks indicate non-specific bands. Δ31-160 variants are not completely deglycosylated by EndoH, resulting in EndoH-resistant fragments (square bracket) which are observed also in reducing conditions (right panel; +/− dithiothreitol (DTT) treatment). Note that endogenous wild-type PrPc was not detected under used conditions.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "METTL14  is  arginine methylated  at its C-terminal IDR in cells.  HEK293  cells expressing Flag-tagged FL or C-terminal IDR-truncated (1-400) METTL14 were lysed and immunoprecipitated with an anti-Flag antibody. Arginine methylation of  immunoprecipitated METTL14 was analyzed by Western blot using two different antibodies that recognize ADMA. the black triangles indicate arginine methylated-METTL14; open triangles indicate the immunoprecipitated METTL14 proteins.",
    "ncbi_link": "Flag: 
METTL14: 57721"
  },
  {
    "caption": "The C-terminal IDR of  METTL14 is essential for its interaction with  PRMT1. HEK293 cells were transfected with GFP-tagged PRMT1 and Flag-tagged FL or C-terminal IDR-truncated (1-400) METTL14. IP was performed using an anti-GFP antibody, and Western blot analysis was performed using anti-GFP and anti-Flag  antibodies.",
    "ncbi_link": "Flag: 
GFP: 
METTL14: 57721
PRMT1: 3276"
  },
  {
    "caption": "Knockdown of PRMT1 expression reduces METTL14 arginine methylation. HEK293 cells were transfected with control  siRNA  (siCtrl) and the siRNA targeting PRMT1 (siPRMT1). METTL14 was immunoprecipitated from these cells, and its methylation level was detected by Western blot analysis using an anti-ASYM26 antibody. * indicates the location of the IgG  heavy chain.",
    "ncbi_link": "PRMT1: 3276"
  },
  {
    "caption": "Arginine methylation  of the C-terminal IDR enhances the RNA methylation activity of the METTL14/METTL3  complex in vitro. In vitro RNA methylation assays were performed by incubating biotin-labeled RNA substrates with METTL3/METTL14 methyltransferase complexes containing WT, hypomethylated (MS023), and arginine methylation-deficient (RK) mutant METTL14 in various concentrations (10-100 nM). The methylation status of the METTL3/METTL14  complex was confirmed by Western blot analysis using an anti-ADMA antibody. Coomassie staining shows the purification of the enzyme complex. Enzymatic activity was measured in counts per minute (c.p.m.) using a scintillation counter. Data from three replicates were analyzed by Student's t-test and shown as mean ± SD. *, p < 0.05; **, p < 0.01; ns, not significant.",
    "ncbi_link": "METTL14: 57721"
  },
  {
    "caption": "m6A  levels are reduced in mESCs expressing arginine methylation-deficient (RK) mutant METTL14. The mRNA purified from WT, Mettl14 KO, KO+WT, and KO+RK mESCs was subjected to  LC-MS/MS analysis to quantify m6A  levels (presented as the m6A/A ratio). data from three independent replicates were analyzed by Student's t-test and shown as mean ± SD. *, p < 0.05; **, p < 0.01, ***, p < 0.001.",
    "ncbi_link": "METTL14: 210529
Mettl14: 210529"
  },
  {
    "caption": "MeRIP (m6A-IP)-qPCR  assays were performed for WT, Mettl14 KO, KO+WT, and KO+RK mESCs to validate the MeRIP-seq results. m6A-negative regions of the transcripts (blue) were included as negative controls. : In (B) , data from three independent replicates were analyzed by Student's t-test and shown as mean ± SD. *, p < 0.05; **, p < 0.01, ***, p < 0.001.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "The expression  of ICL repair genes is reduced in mESCs expressing arginine methylation-deficient mutant (RK) METTL14. Total cell lysates from WT, Mettl14  KO, KO+WT, and KO+RK mESCs  were subjected to Western blot  analysis  using the indicated antibodies.",
    "ncbi_link": "Mettl14: 210529
METTL14: 210529"
  },
  {
    "caption": "mESCs  expressing arginine methylation-deficient mutant (RK) METTL14 are sensitive to ICL damage induced by MMC. WT, Mettl14 KO, KO+WT, and KO+RK  mESCs were treated with various concentrations of MMC  for 4 days before  cell viability was measured.   Similar to (A), except that mESCs were treated with cisplatin, another ICL-inducing chemical, at various concentrations.   In both (A) and (B), each point represents the average of three independent replicates and error bars represent standard deviation (SD). Statistical analysis was performed using Student's t-test. *, p < 0.05.",
    "ncbi_link": "METTL14: 210529
Mettl14: 210529"
  },
  {
    "caption": "MST analysis of the binding interactions between Sir4 H‑BRCT and Cy5-labeled phospho (filled circles) and non-phospho peptides (empty circles) from Esc1, Ty5 and Ubp10. KD = equilibrium dissociation constant. ΔFnorm values were divided by the amplitude of the saturation level, resulting in the fraction bound (from 0 to 1) for each data point. Data are represented as the mean ± SEM from ≥3 independent measurements.",
    "ncbi_link": "Sir4: 851813"
  },
  {
    "caption": "Example images of Nup49-RFP Sir4-GFP in wild-type (wt) cells (GA-10372; row 1); sir4 RKR cells (GA-10373; row 2); wt cells transformed with either empty plasmid (row 3), plasmid overexpressing wt Sir4 H‑BRCT (row 4), or plasmid overexpressing RKR mutant Sir4 H‑BRCT (row 5). The bar indicates 2 μm.",
    "ncbi_link": "sir4: 851813
Sir4: 851813"
  },
  {
    "caption": "Top: Schematic representation of the TEL7L::URA3 reporter used to assay silencing at telomeres. Bottom: wt cells (GA-503) transformed with either an empty plasmid (row 1), plasmid overexpressing wt Sir4 H‑BRCT (row 2), or plasmid overexpressing RKR mutant Sir4 H‑BRCT (row 3). Cells lacking endogenous sir4 (GA-5822) (row 4). Cells were grown in the absence of uracil and plated as 1:5 serial dilutions onto control YPAD or YPAD lacking uracil plates and imaged after 2 days. Top: Schematic representation of the HMR-EΔB::TRP1 reporter gene locus used for assaying silencing at the HMR locus. Bottom: wt cells (GA-485) transformed with plasmids as in panel D. Cells lacking endogenous sir4 (GA-6888) (row 4). Cells were grown in the absence of tryptophan and plated as 1:5 serial dilutions onto YPAD or YPAD lacking tryptophan plates and imaged after 2 days.",
    "ncbi_link": "Sir4: 851813
sir4: 851813
TRP1: 851570
URA3: 856692"
  },
  {
    "caption": "Volcano plot showing proteins that interact with wt Sir4 H‑BRCT but not with the RKR mutant (upper right quadrant).",
    "ncbi_link": "Sir4: 851813"
  },
  {
    "caption": "MST analysis of the binding interactions between Sir4 H‑BRCT and Cy5-labeled phospho (filled circles) and non-phospho peptides (empty circles) from Tom1 and Cbf1. KD represents the equilibrium dissociation constant. The KD for interactions with the non-phospho peptides could not be determined (n.d.). ΔFnorm [0/00] represents the change in fluorescence during thermophoresis normalized to the initial fluorescence. Data are represented as the mean ± SEM from at least 3 independent measurements.",
    "ncbi_link": "Sir4: 851813"
  },
  {
    "caption": "Extracts from asynchronous cultures of strains Sir4-Myc Tom1-HA (GA-10645), Sir4-RKR-Myc Tom1-HA (GA-10646), Tom1-HA (GA-10647) and Sir4-Myc (GA-10199) were subjected to anti-Myc IP and western blotting with indicated antibodies in the presence and absence of lambda phosphatase.",
    "ncbi_link": "Myc: 
Sir4: 851813
Tom1: 852068"
  },
  {
    "caption": "MST analysis of the binding interactions between Dbf4 H‑BRCT and Cy5-labeled phospho (filled circles) and non-phospho peptides (empty circles) from Esc1 and Ubp10. KD = equilibrium dissociation constant, which could not be determined (n.d.) for non-phospho peptides. ΔFnorm [0/00] represents the change in fluorescence during thermophoresis normalized to the initial fluorescence. Data are the mean ± SEM from ≥3 independent measurements.",
    "ncbi_link": "Dbf4: 851623"
  },
  {
    "caption": "CLSM images showing nucleolar co‐localization of NCL (immunofluorescence) with aluRNA (RNA FISH) but not with L1‐repeat RNA. Cells were pre‐treated in situ with RNase A or an RNase inhibitor. Nuclei were counterstained with DAPI. The signal intensity of nucleolar aluRNA was two‐fold higher compared to nucleoplasmic signal (n = 92, P‐value 0.05, t‐test).",
    "ncbi_link": "alu: "
  },
  {
    "caption": "CLSMimages showing NPM (immunofluorescence, red) in HeLacells transfected with control ASO, aluRNAASO, or treated with transfection reagent only (mock). Nuclei were counterstained with DAPI (blue). A fraction of 80 ± 8% of the cells treated with aluRNAASO (n = 143) showed irregular nucleoli or dispersed nucleoli (53% of the cells). Only 26 ± 9% of the cells treated with control ASO presented abnormal nucleoli, with none of them showing a dispersion of nucleolar domains (n = 123), P‐value 0.01, t‐test.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "CLSM images showing NCL localization (immunofluorescence), aluRNA (RNA FISH) and DNA (DAPI). Transfection of HeLa cells was done as in (A).",
    "ncbi_link": "alu: "
  },
  {
    "caption": "Levels of 47Spre‐rRNA in mock‐, control ASO‐ and aluRNAASO‐treated HeLacells. Top: Northern blot. Center: Agarose gel electrophoretic analysis of RNA. Bottom panel: Quantification from RT-qPCR levels of 47Spre‐rRNA normalized to 18SrRNA. Error bars represent the standard deviation (n = 6). **P‐value 0.01, t‐test.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "HeLa cells were transfected with an empty vector or plasmids expressing aluRNA or L1‐repeat RNA and GFP from a separate promoter. Transfected cells were identified by GFP fluorescence, and nucleoli volumes were evaluated based on the immunofluorescence signal of the nucleolar marker NPM. The graphs show that the volume of nucleoli is increased by 30% in the presence of ectopic aluRNA (± 95% CI, n = 20). **P‐value 0.01, t‐test. Scale bar, 10 μm.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "CLSM live‐cell imaging of RFP‐NCL in cells transfected with a plasmid expressing aluRNA and imaged for 10 h. The arrows indicate nucleolar domains displaying time‐dependent increase in the nucleolar size or fusion of two domains into one. Scale bars, 10 μm.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "Graphs represent the intensity of nucleolar fluorescence signals as percentage of the intensity of nuclear signals and reveal a 27% increase in the presence of ectopic aluRNA (± 95% CI, n = 30). **P‐value 0.01, *P‐value = 0.01, t‐test.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "CLSM images of MS2‐tagged aluRNA or MS2‐tagged control RNA (a fragment from the transcript of the CDV3 gene). MS2‐loop‐containing RNAs were visualized by RNA FISH using MS2‐loop‐specific FISH probes (green); nucleoli were visualized by immunofluorescence of NCL (red).",
    "ncbi_link": "alu: 
CDV3: 55573"
  },
  {
    "caption": "The top panel depicts the experimental approach used to tether MS2‐loop‐containing RNAs to lacO arrays via a GFP‐tagged LacI‐MS2 coat fusion protein. The lacO arrays were stably integrated in the genome of U2OS cells. In the bottom panel, CLSM images of U2OS cells are shown that were transfected with MS2‐aluRNAR. They reveal the localization of LacI‐GFP‐MS2 and NCL (immunofluorescence, red). The arrow indicates the lacO array, which is associated with a nucleolar domain.",
    "ncbi_link": "lacO: 
alu: "
  },
  {
    "caption": "MS2‐loop‐containing forward aluRNA or aluRNAL or aluRNAR were recruited to the single stably integrated lacO array in the U2OS F4IIB8 cell line. The propensity for nucleolar localization was evaluated as the average number of lacO arrays with tethered RNA detected in nucleoli (± 95% CI) and is plotted in the bar chart. Calculations are based on analysis of more than 100 cells. **P‐value 0.01, t‐test, from the analysis of two independent biological replicates. As controls, transcripts of the MS2 loops only, the MS2‐CDV3, MS2‐RepA, MS2‐STARD7 and MS2‐CORO1C RNAs were used. The inset shows a CLSM image with MS2‐GFP‐LacI (green) and NPM (red, immunofluorescence) after recruitment of MS2‐aluRNA.",
    "ncbi_link": "alu: 
CDV3: 55573
CORO1C: 23603
RepA: 8094872
STARD7: 56910"
  },
  {
    "caption": "Top: Scheme illustrating the experimental approach used to tether GFP‐tagged LacI fusion proteins via a GFP‐binding protein (GBP) to lacO arrays. The lacO arrays are stably integrated in the genome of U2OS cells. Bottom: CLSM images showing the localization of GBP‐LacI‐RFP, GFP‐NCL, GFP‐NPM or GFP‐TIP5‐RBD fusion proteins relative to aluRNA that was visualized by RNA FISH. The insets contain an enlarged image of one of the lacO loci.",
    "ncbi_link": "alu: "
  },
  {
    "caption": "CLSM images of UBF (immunofluorescence, green) or rDNA (DNA FISH, green) and DNA (DAPI, blue) after knockdown of NCL and NPM by siRNA in HeLa cells.",
    "ncbi_link": "NCL: 4691
NPM: 4869"
  },
  {
    "caption": "B, H1299 cells transfected with a control siRNA (siCont.) or an RNF20-specific siRNA (siRNF20) and a wild-type H2B (H2BWT) or a K120R-mutated H2B (H2BK120R) were treated with 12 μM erastin (+) or untreated (-) for 24 h. Representative phase-contrast images were recorded (magnification, ×20), and the surviving cells were counted. Data information: Bars and error bars are mean±s.d., n=3 independent repeats. Two-tailed unpaired Student's t-test was performed. *: p<0.05, **: p<0.01.",
    "ncbi_link": "H2B: 8349
RNF20: 56254"
  },
  {
    "caption": "E, Control H1299 cells (transfected with siCont. or H2BWT) and H2Bub1-depleted H1299 cells (transfected with siRNF20 or H2BK120R) were treated with erastin either with or without a ferroptosis-specific inhibitor, ferrostatin-1 (2 μM), for 24 h. Representative phase-contrast images were recorded (magnification, ×20), and the surviving cells were counted. Data information: Bars and error bars are mean±s.d., n=3 independent repeats. Two-tailed unpaired Student's t-test was performed. *: p<0.05, **: p<0.01.",
    "ncbi_link": "H2B: 8349
RNF20: 56254"
  },
  {
    "caption": "A, qRT-PCR (left) and Western blot (right) analyses of H1299 cells transfected with a control siRNA (siCont.) or an RNF20-specific siRNA (siRNF20) and a wild-type H2B (H2BWT) or a K120R-mutated H2B (H2BK120R) for 24 h. Data information: Bars and error bars are mean±s.d., n=3 independent repeats. Two-tailed unpaired Student's t-test was performed. *: p<0.05, **: p<0.01.",
    "ncbi_link": "H2B: 8349
RNF20: 56254"
  },
  {
    "caption": "B, Chromatin immunoprecipitation (ChIP) assay was carried out with anti-H2Bub1 antibodies in H1299 cells (left) or 293T cells either untreated or treated with 20 μM erastin for 24 h (right). The intergenic region was used as a negative control for the occupancy of H2Bub1. Data information: Bars and error bars are mean±s.d., n=3 independent repeats. Two-tailed unpaired Student's t-test was performed. *: p<0.05, **: p<0.01.",
    "ncbi_link": "H2B: 8349"
  },
  {
    "caption": "Western blot analysis was performed with H1299 or Hep3B cells transfected with a Flag-tagged p53 or an empty plasmid (Cont.) for 48 h.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "Western blot analysis was performed with H1299 cells transfected with a Flag-tagged p53 or an empty plasmid (Cont.) for 48 h.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "C, Immunofluorescence (IF) assay for H1299 cells transfected with a Flag-tagged p53 (Flag-p53) or an empty plasmid (Cont.) for 48 h. Representative images are shown (magnification, ×40). Arrowhead indicates a Flag-p53 overexpressing cell.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "D, Western blot analysis was performed with H1299 transfected with a Flag-tagged p53 or an empty vector (Cont.) for 48 h.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "E, 293T cells transfected with a control siRNA (siCont.) and three p53-specific siRNAs (sip53) were subjected to Western blot analysis.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "H, H1299 cells transfected with a Flag-tagged p53 or an empty plasmid (Cont.) were analyzed by micrococcal nuclease (MNase) digestion assay.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "I, Western blot analysis of H1299 cells transfected with a wild-type p53 (p53-WT) or two \"gain-of-function\" mutants (p53-R273H and p53-R175H) for 48 h.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "B, H1299 cells were transfected with an empty vector (Cont.), a Flag-tagged p53, a USP7-specific shRNA, or the last two plasmids together for 48 h. Western blot analysis was then performed.",
    "ncbi_link": "Flag: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "C, Nuclear and cytosolic extracts were differentially prepared from H1299 cells transfected with a Flag-tagged p53 or an empty plasmid (Cont.). Western blot analysis was then performed.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "D, H1299 cells transfected with a Myc-tagged USP7 or a Myc-tagged USP7 together with a Flag-tagged p53 were subjected to IF analysis (upper). A549 cells transfected with a p53-specific siRNA or a control siRNA (siCont.) were examined by IF analysis, and the RNAi efficiency is shown (lower). Representative images are shown (magnification, ×40).",
    "ncbi_link": "Flag: 
Myc: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "F, IF analysis of A549 cells transfected with a Myc-tagged wild-type USP7 (Myc-USP7-WT) or three Myc-tagged truncated mutants. Representative images are shown (magnification, ×40).",
    "ncbi_link": "Myc: 
USP7: 7874"
  },
  {
    "caption": "G, H1299 cells were transfected with a Flag-tagged p53 or an empty vector together with a USP7-specific siRNA or a control siRNA as indicated for 48 h. Cells were then harvested and subjected to a MNase digestion assay.",
    "ncbi_link": "Flag: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "D, Co-IP analysis for H1299 cells transfected with a Flag-tagged p53 or an empty plasmid (Cont.) treated with a USP7-specific inhibitor P5091.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "B, H1299 cells were transfected with Flag-tagged p53 for 24 h and then treated with 12 μM erastin or untreated for another 24 h. Co-IP analysis was performed with antibodies against Flag.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "C, H1299 cells transfected with Flag-tagged p53 were treated with erastin or untreated for 24 h. Nuclear and cytosolic extracts were differentially prepared and subjected to Western blot analysis.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "D, 293T cells transfected with a p53-specific siRNA, a USP7-specific siRNA, or a control siRNA (siCont.) were treated with 20 μM erastin or untreated for 24 h as indicated. Western blot analysis was then performed.",
    "ncbi_link": "p53: 7157
USP7: 7874"
  },
  {
    "caption": ", qRT-PCR (above) and Western blot (below) analyses for H1299 cells transfected with a Flag-tagged p53 or an empty plasmid together with a USP7-specific siRNA or a control siRNA (siCont.) as indicated. Data information: Bars and error bars are mean±s.d., n=3 independent repeats.",
    "ncbi_link": "Flag: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "F, ChIP analysis of H1299 cells transfected with a Flag-tagged p53 or an empty plasmid together with a USP7-specific siRNA or a control siRNA (siCont.) as indicated. Data information: Bars and error bars are mean±s.d., n=3 independent repeats.",
    "ncbi_link": "Flag: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "G, H1299 cells transfected with Flag-tagged p53 were treated with 12 μM erastin or untreated for 24 h. ChIP analysis with antibodies against Flag or USP7 was performed. Data information: Bars and error bars are mean±s.d., n=3 independent repeats.",
    "ncbi_link": "Flag: 
p53: 7157"
  },
  {
    "caption": "H, 293T cells transfected with a p53-specific siRNA, a USP7-specific siRNA or a control were treated with 20 μM erastin or untreated for 24 h. ChIP analysis was performed with anti-H2Bub1 antibodies. Data information: Bars and error bars are mean±s.d., n=3 independent repeats.",
    "ncbi_link": "p53: 7157
USP7: 7874"
  },
  {
    "caption": "A, H1299 cells transfected with a Flag-tagged p53 or an empty plasmid together with a USP7-specific siRNA or a control siRNA (siCont.) as were treated with 12 μM erastin (+) or untreated (-) for 24 h as indicated. Representative phase-contrast images were recorded (magnification, ×20), and the surviving cells were counted. Data information: Bars and error bars are mean±s.d., n=3 independent repeats. Two-tailed unpaired Student's t-test was performed. *: p<0.05.",
    "ncbi_link": "Flag: 
p53: 7157
USP7: 7874"
  },
  {
    "caption": "b, Experimental procedure in vivo: flow chart and pictures of an in vivo screen to identify DUBs that promote breast cancer metastasis in mice (left panel). Low metastatic MDA-MB-231-Luciferase/GFP breast cancer cells were infected with viral vectors expressing DUB cDNAs and subsequently intracardially injected into nude mice. The mice were monitored for 4 weeks by in vivo BLI: of the 30 mice injected with cells expressing DUB cDNA pool; 3 had metastases in the brain and bone (3/30), 4 had metastases on the back and in the bone (4/30), and 9 had micro-metastasis (9/30); the 30 mice injected with control cells showed no detectable metastasis (30/30). Right panel: hints of the identified DUBs were shown.",
    "ncbi_link": "GFP: 
Luciferase: "
  },
  {
    "caption": "c, The expression distribution of USP8 gene in breast cancer tumor tissues (n = 1097) and normal tissues (n = 572), where the horizontal axis represents different groups of samples, the vertical axis represents the gene expression distribution (left panel). The box-and-whisker plots represent the medians (middle line), first quartiles (lower bound line), third quartiles (upper bound line), and the ±1.5× interquartile ranges (whisker lines). Kaplan-Meier curves showing the metastasis-free survival of individuals was negatively correlated with USP8 expression by log-rank test (right panel).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "d, MCF10A-RAS cells infected with control (Co.sh) or USP8 shRNA lentivirus (# 1 and # 2) were analyzed in a tumor sphere assay. The number of the mammospheres with diameter > 60 μm was quantified. The graph shows the number (No.) of tumor spheres per 5 × 103 cells seeded. Scale bar 50 μm",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "e, MCF10A-RAS cells infected with control (Co.sh) or USP8 shRNA lentivirus (# 1 and # 2) were subcutaneously injected into nude mice at the indicated numbers. Mean of tumor volumes at week 5 (n = 10 mice for each group).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "f, Microscopy pictures of representative images of zebrafish tail fin injected with control or USP8 stably depleted-MDA-MB-231 cells at 5 days post injection, n = 20 for each group. g, The final invasive areas of zebrafish embryos displaying invasion and experimental metastasis at 5 dpi (left panel); Percentage of embryos injected with control or USP8 stably depleted MDA-MB-231 cells (# 1 and # 2) displaying metastasis at 1, 3 and 5 days post injection (right panel).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "h, Bioluminescent images of three representative mice from each group (n = 6) at week 6 injected into left heart ventricle with control or MDA-MB-231 cells stably depleted of endogenous USP8 with two independent shRNA (# 1 and # 2). i, BLI signal (left panel), number of bone metastasis of every mouse (middle panel) and the percentage of bone metastasis free mice in each experimental group (n = 6 mice per group) followed in time as in h (right panel).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "c, Experimental procedure in vivo: MDA-MB-231 cells were intracardially injected into nude mice (n = 10). qRT-PCR analysis of bone metastatic cells showing the correlations between USP8 and Snai1 or Snai2 (Slug) in cells isolated from mutiple metastatic nodules (n = 21) from mice.",
    "ncbi_link": "Snai1: 6615
Slug: 6591
Snai2: 6591
USP8: 9101"
  },
  {
    "caption": "d, 3D spheroid invasion assay of MCF10A-Ras cells showing USP8 wt increased TGF-β-induced invasion. Relative invasion was quantified and shown in the right panel.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "e, MCF10A-Ras cells stably expressing control vector (Co.vec), USP8 wt or USP8 cs were injected into the blood circulation of 48-hpf zebrafish embryos. SB431542 (5 μM) was added to the zebrafish environment. Representative images of zebrafish at 5 dpi (left panel); the experimental metastatic areas (middle panel) and percentage of embryos showing metastasis (right panel) are shown, n = 20.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "f, Diagram of DUB cDNA screening data of TGF-β-induced SMAD3/ SMAD4-dependent CAGA12-Luc transcriptional reporter in HEK293T cells. The X- and Y-axes are the relative luciferase activity in two replicates.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "g, CAGA12-Luc transcriptional response of HEK293T cells transfected with USP8 wt/cs or shUSP8 (#1 and #2) as indicated and treated with TGF-β (1 ng/ml) overnight.",
    "ncbi_link": "Luc: 
USP8: 9101"
  },
  {
    "caption": "h, Heatmap of TGF-β target genes by qRT-PCR analysis in control or MCF10A-RAS cells stably depleting USP8 (#1 and #2 shRNA) or expressing USP8 wt/cs and treated with or without TGF-β (2.5 ng/ml) for 8 hrs. Appendix Table S2 for details.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "i, Immunoblot analysis of total cell lysates, immunoprecipitates derived from control and USP8 stably depleted (#1 and #2 shRNA) (left panel) and USP8 wt/cs over-expressed (right panel) MDA-MB-231 cells treated with TGF-β (2.5 ng/ml) for indicated time points.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "j, Immunofluorescence and 4, 6-diamidino-2-phenylindole (DAPI) staining of HaCaT cells infected with control or USP8 wt/cs and treated with TGF-β (2.5 ng/ml) and SB431542 (10 μM) for 72 hrs. Scale bar, 20 μm.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "k, Immunoblot analysis of cell lysate of control and USP8 stably depleted-MCF10AR-RAS (MII) cells treated with TGF-β (5 ng/ml) for 48 hrs (left); Immunoblot analysis of cell lysate of control and USP8 wt or USP8 cs stably expressed-MCF10AR-RAS (MII) cells treated with TGF-β (5 ng/ml) or SB431542 (10 μM) for 48 hrs (right).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "f, IB of TCL and immunoprecipitants derived from HA-Ub stably expressed HEK293T cells transfected with Myc-USP8 wt/cs (left panel) or infected with control (Co.sh) or USP8 shRNA lentivirus (#1 and #2) (right panel) and treated with TGF-β (5 ng/ml) as indicated.",
    "ncbi_link": "Myc: 
USP8: 9101"
  },
  {
    "caption": "g, IB of HeLa cells stably expressing TβRII-HA and transfected with control empty vector (Co.vector) and Flag-USP8 wt/cs plasmids and treated with CHX (20 μg/ml) for indicated time points.",
    "ncbi_link": "Flag: 
USP8: 9101"
  },
  {
    "caption": "h, Immunoblot analysis of MCF10A-RAS cells stably expressing USP8 wt/cs or USP8 shRNA (#1 and #2).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "i, Immunoblot analysis of biotinylated TβRII in MDA-MB-231 cells ectopically expressing USP8 wt/cs and treated with TGF-β (5 ng/ml) as indicated (left panel). Quantification of the band intensities is shown in right panel. Band intensity was normalized to the t=0 controls (right panel). n = 2 technical replicates.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "j, Immunoblot analysis of biotinylated TβRII in MDA-MB-231 cells infected with lentivirus encoding control shRNA (Co.sh), USP8 shRNA (# 1 and # 2) and treated with TGF-β (5 ng/ml) as indicated (left panel). Quantification of the band intensities is shown in right panel. Band intensity was normalized to the t=0 controls (right panel).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "a, Comparison of the pre-treatment levels of USP8 mRNA in patient-derived tissue samples by qRT-PCR (left panel), enzyme activity of USP8 in patient-derived tissue samples by Ub-VME (middle panel) and TβRII+ crEVs level in the plasma from breast cancer patients by ELISA (right panel) between breast cancer patients with or without clinical response to PTX. R, responders; n = 16; NR, non-responders; n = 14.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "b, Pearson correlation of the USP8 mRNA or USP8 enzyme activity in patient-derived tissue samples with the EV-TβRII levels in the plasma from breast cancer patients without clinical response to PTX as in a (NR, n = 14).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "e, TβRII+ crEVs (left panel), the USP8 enzyme activity (midde panel) and USP8 mRNA (right panel) from breast cancer patients with or without clinical response to combined therapy using anti-PD-L1 (Atezolizumab) and paclitaxel. R, responders; n = 10 (left panel), n = 5 (middle and right panels, only 5 patient-derived tissue samples obtained). NR, non-responders; n = 10 (left panel), n = 6 (middle and right panels, only 5 patient-derived tissue samples obtained).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "Experimental procedure in vivo: MDA-MB-231 cells were intracardially injected into nude mice. Bioluminescent imaging (BLI) of representative mice from each group at week 6 injected with control (n = 9) or MDA-MB-231 cells stably ovexpressed with USP8-WT (n = 7) or USP8-CS (n = 9). BLI images are shown (f (left panel)). BLI signal of each mice (f (middle panel)) and number of bone metastasis (f (right panel)) of every mouse",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "Experimental procedure in vivo: MDA-MB-231 cells were intracardially injected into nude mice. mice from each group at week 6 injected with control (n = 9) or MDA-MB-231 cells stably ovexpressed with USP8-WT (n = 7) or USP8-CS (n = 9). the percentage of bone metastasis free mice survival in each experimental group followed in time (g).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "Experimental procedure in vivo: MDA-MB-231 cells were intracardially injected into nude mice. mice from each group at week 6 injected with control (n = 9) or MDA-MB-231 cells stably ovexpressed with USP8-WT (n = 7) or USP8-CS (n = 9). Fold change of circulating EV-TβRII by ELISA analysis in plasma samples of mice in each experimental group at week 6 (h).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "nude mice were tail vein-injected with 4T07-Luc cells (5 × 105 cells per mouse) expressing control vector or doxycycline-inducible USP8-wt/cs and tumors were grown for 2 weeks, followed by the administration of doxycycline (n = 6 for each group) Normalized BLI signals (left panel) and representative mice (right panel) from each group at the indicated times (j).",
    "ncbi_link": "USP8: 84092"
  },
  {
    "caption": "nude mice were tail vein-injected with 4T07-Luc cells (5 × 105 cells per mouse) expressing control vector or doxycycline-inducible USP8-wt/cs and tumors were grown for 2 weeks, followed by the administration of doxycycline (n = 6 for each group) Immunoblot analysis of the circulating EVs from plasma in mice (k).",
    "ncbi_link": "Luc: 
USP8: 84092"
  },
  {
    "caption": "nude mice were tail vein-injected with 4T07-Luc cells (5 × 105 cells per mouse) expressing control vector or doxycycline-inducible USP8-wt/cs and tumors were grown for 2 weeks, followed by the administration of doxycycline (n = 6 for each group) ELISA analysis of circulating exosomal TβRII level in plasma samples of mice at the indicated times (l).",
    "ncbi_link": "Luc: 
USP8: 84092"
  },
  {
    "caption": "b, Heatmap shows the up-regulated genes upon USP8 over-expression and the down-regulated genes upon USP8 depletion when compared with control MDA-MB-231 cells by RNA-seq analysis (left panel). qRT-PCR analysis of control or MDA-MB-231 cells stably over-expressing USP8 (USP8 OE) or USP8 shRNA (right panel).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "e, FACS analysis of EVs from 4T1 and MDA-MB-231 cells infected with lentivirus encoding control shRNA (Co.sh) or USP8 shRNA.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "f, Immunoblot analysis of EVs from MDA-MB-231 cells infected with lentivirus encoding control shRNA (Co.sh) or USP8 shRNA (#1 & #2).",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "g, Immunoblot analysis of the EVs derived from MDA-MB-231 cells ectopically expressing USP8 wt/cs.",
    "ncbi_link": "USP8: 9101"
  },
  {
    "caption": "h, Experimental procedure in vivo: BALB/c mice were nipple injected with 4T1-Luc cells (5 × 105 cells per mouse) expressing control shRNA or doxycycline-inducible shRNA targeting USP8 (shUSP8) and tumors were grown for 3 weeks, followed by the administration of doxycycline for 3 weeks (n = 6 for each group). i, Quantification of the percentage of TβRII+ crEVs in plasma samples from mice at day 24. j, Immunoblot analysis of tumor and the TEVs (left panel) and quantification of the percentage of TβRII+ EVs (right panel) in plasma samples from mice at day 42. k, Normalized photon flux at the indicated times. l,",
    "ncbi_link": "Luc: 
USP8: 84092"
  },
  {
    "caption": "d, Effect of USP8 inhibitor (5 μM) on SMAD3/SMAD4-dependent CAGA12-Luc transcriptional response induced by TGF-β (2.5 ng/ml) for 16 h in HEK293T cells transfected with control vector (Co.vec) or USP8 wt/cs. n = 3 biological replicates.",
    "ncbi_link": "Luc: 
USP8: 9101"
  },
  {
    "caption": "k-n, Experimental procedure in vivo MDA-MB-231-Luc cells (1 × 105 per mouse) were intracardially injected into nude mice (n = 7 for each group). USP8 inhibitor (1 mg/kg) was injected at day 1 via intraperitoneal injection every the other day for three weeks. Normalized BLI signals (left panel) and BLI imaging of three representive nude mice from each group at week 6 (right panel) were shown (k). Percentage of metastasis-free survival in each experimental group followed in time (l). Number of bone metastasis nodules (m). Percentage of TβRII+ crEVs in plasma samples from mice (left panel) and immunoblot analysis of metastatic tumor nodule in mice and circulating EVs from plasma (right panel) (n).",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Oxidation kinetics experiment to investigate the influence of MIA40 on AK2 maturation. Experiment was performed as described in (D), except that 72 h before experiments cells were transfected with control siRNA or siRNA directed against MIA40. Endogenous AK2 oxidation depends on MIA40. Reported values are the mean of 3 independent experiments; error bars represent ±SD. Student's t-test was performed. * represents p<0.05, ** represents p<0.01 and *** represents p<0.001.",
    "ncbi_link": "MIA40: 131474"
  },
  {
    "caption": "Influence of AK2 cysteines on the AK2 redox state. Cells expressing single cysteine to serine mutants of AK2-HA (isoform A) were lysed after NEM treatment, and analyzed by inverse redox shift assay using mmPEG12, SDS-PAGE and immunoblot against the HA tag. AK2C42S and AK2C92S are present in their completely reduced state indicating presence of a disulfide bond between both cysteines.",
    "ncbi_link": "AK2: 204"
  },
  {
    "caption": "Influence of AK2 cysteines on cellular localization. Cells expressing single cysteine to serine mutants of AK2-HA (isoform A) were fixed and analyzed by immunofluorescence. The colocalization of AK2-HA variants with Mitotracker was quantified using Cellprofiler (Pearson's correlation coefficient). C42 and C92 are critical for mitochondrial localization of AK2. The C40S mutant exhibits significantly decreased colocalization with mitochondria. A Kruskall-Wallis rank sum test/ Dunn-test was performed. Numbers of analysed cells are indicated in the plot. *** represents p-value <0.001 compared to wild-type. The black horizontal line represents the median. Data information: Scale bars: 10 μm.",
    "ncbi_link": "HA: 
AK2: 204"
  },
  {
    "caption": "Steady state levels of endogenous AK2 in presence and absence of MIA40. 72 h before experiments, HeLa cells were transfected with control siRNA or siRNAs directed against MIA40 or ALR. Cell lysates were analysed by immunoblot against the indicated proteins. MIA40 depletion led to a strong decrease in AK2 and ALR levels but not of the control proteins. ALR depletion did not affect AK2 levels. Reported values are the mean of 3 independent experiments; error bars represent ±SD. Student's t-test was performed. * represents p<0.05,.",
    "ncbi_link": "MIA40: 131474
ALR: 2671"
  },
  {
    "caption": "Stability of endogenous AK2 in the presence and absence of MIA40. 72 h before experiments HeLa, cells were transfected with control siRNA or siRNAs directed against MIA40. Cells were pulse labeled for 10 min with [35S]-methionine and chased with cold methionine for the indicated times. The chase was stopped by cell lysis, and AK2 was isolated by denaturing immunoprecipitation. Eluates were analyzed by SDS-PAGE and autoradiography. Stability of endogenous AK2 is significantly decreased upon depletion of MIA40. Reported values are the mean of 3 independent experiments; error bars represent ±SD. Student's t-test was performed; * represents p-value <0.05 compared to wild-type.",
    "ncbi_link": "MIA40: 131474"
  },
  {
    "caption": "Steady state levels of AK2-HA cysteine variants. AK2C40S,C42S,C92S-HA and AK2WT-HA were expressed in the presence or absence of proteasomal inhibitor MG132. Protein levels at steady state were analysed by immunoblot. All variants are stabilized by proteasomal inhibition. Reported values are the mean of 3 (AK2WT-HA) or 5 (AK2C40S,C42S,C92S-HA) independent experiments; error bars represent ±SD. ANOVA/Tukey's post-hoc test was performed. *** represents p<0.001.",
    "ncbi_link": "AK2: 204"
  },
  {
    "caption": "Steady state levels of AK2-HA cysteine variant. 72 h before experiments HEK293 cells were transfected with control siRNA or siRNAs directed against the proteasomal subunits PSMB3 and PSMC5. AK2C40S,C42S,C92S-HA was stabilized by decreased proteasome levels. Reported values are the mean of 4 independent experiments; error bars represent ±SD. Student's t-test was performed. * represents p<0.05.",
    "ncbi_link": "PSMB3: 5691
PSMC5: 5705"
  },
  {
    "caption": "Steady state levels of AK2C40S,C42S,C92S-HA in presence and absence of DPP8 and DPP9. 72 h before experiments, HEK293 cells stably expressing AK2C40S,C42S,C92S-HA were transfected with control siRNA or siRNAs directed against DPP8 or/and DPP9. Cell lysates were analysed by immunoblot against the indicated proteins. DPP9 depletion led to an increase in AK2C40S,C42S,C92S-HA levels, while DPP8 depletion did not. Combined depletion of DPP8 and DPP9 increased AK2C40S,C42S,C92S-HA levels even further. This indicates that DPP9 is the main peptidase and DPP8 can serve as its backup. White and black arrow heads indicate the endogenous and HA-tagged AK2, respectively. The gray arrow head indicates the DPP9 band. Reported values are the mean of 3 independent experiments; error bars represent ±SD. ANOVA/Tukey's post-hoc test was performed. * represents p<0.05, ,## represent p<0.01 and ***,### represent p<0.001.",
    "ncbi_link": "DPP8: 54878
DPP9: 91039"
  },
  {
    "caption": "Steady state levels of endogenous AK2 in presence and absence of DPP9 and MIA40. 72 h before experiments HeLa cells were transfected with control siRNA or siRNAs directed against MIA40 and/or DPP9. Cell lysates were analysed by immunoblot against the indicated proteins. If import of endogenous AK2 was prevented by depletion of MIA40, then concomitant depletion of DPPs increased its levels. Strikingly, depletion of DPP9 alone also increased the levels of endogenous AK2. Reported values are the mean of 3 independent experiments; error bars represent ±SD. ANOVA/Tukey's post-hoc test was performed. ** represents p<0.01.",
    "ncbi_link": "MIA40: 131474
DPP9: 91039"
  },
  {
    "caption": "Steady state levels of AK2-HA variants with mutated N-termini upon incubation with either 1G244 or vehicle control. HEK293 cells stably expressing AK2-HA variants were lysed and subjected to immunoblot against the indicated proteins. Levels of DPP8/9-insensitive AK2 variants are strongly increased. Reported values are the mean of 4 independent experiments; error bars represent ±SD. ANOVA/Tukey's post-hoc test was performed. ** represents p<0.01 and ###, *** represents p<0.001. Asterisk denominate statistical comparison with respective control, and hash tag represents comparison to N-WT.",
    "ncbi_link": "AK2: 204"
  },
  {
    "caption": "Localization of DPP9-insensitive AK2-HA variants. Experiment was performed as described in Figure 2C. Compared to the wild type, DPP9-insensitive and import-competent AK2-HA variants co-localized with cytosolic markers indicating partial cytosolic localization. The colocalization of AK2-HA variants with Mitotracker was quantified using Fiji (Pearson's correlation coefficient). A one-way ANOVA with post-hoc Tukey test was performed. Numbers of analysed cells are indicated in the plot. ** represents p<0.01. Data shown in Figures 2C, 5B, S2 and S5 are derived from the same experiments. The black horizontal line represents the median. Data information: Scale bars: 10 μm.",
    "ncbi_link": "AK2: 204"
  },
  {
    "caption": "Steady state levels of NDUFB10 variants upon incubation with the DPP9 inhibitor 1G244. Cells were treated for 24h with inhibitor or DMSO as control, and were then analysed by immunoblot against the indicated proteins. NDUFB10C107S is stabilized upon DPP9 inhibition. Reported values are the mean of 4 independent experiments; error bars represent ±SD. Student's t-test was performed for the respective control and treatment samples. ** represents p<0.01.",
    "ncbi_link": "NDUFB10: "
  },
  {
    "caption": "Localization of NDUFB10 variants upon 1G244 treatment. Experiment was performed as in (C) except that mitochondria were isolated and the fractions analysed by immunoblot against the indicated proteins. Mitochondria contain increased NDUFB10C107S levels after DPP9 inhibition. Reported values are the mean of 2 independent experiments; error bars represent ±SD. Student's t-test was performed. * represents p<0.05.",
    "ncbi_link": "NDUFB10: "
  },
  {
    "caption": "A) TUBB1 is expressed in the developing human thyroid at 8 gestational weeks (GW), 10 GW, and 12 GW and in the adult human thyroid: quantitative PCR results normalized to one of three thyroid tissues at 8 GW value (in black) and peptidylprolyl isomerase A. Experiments with at least three tissues per stage. Statistical comparisons versus 8 GW (in black) using ANOVA test showed no significant differences",
    "ncbi_link": "peptidylprolyl isomerase A: 
TUBB1: 81027"
  },
  {
    "caption": "B) Tubb1 is expressed in the developing mouse thyroid at E13.5, E15.5, and E17.5 and in the adult mouse thyroid: quantitative PCR results normalized to one of three thyroid tissues at E13.5 value and peptidylprolyl isomerase A. Experiments with at least three tissues per stage. Statistical comparisons versus E13.5 (black), **p<0.01 using ANOVA test",
    "ncbi_link": "peptidylprolyl isomerase A: 
Tubb1: 545486"
  },
  {
    "caption": "C) Sorted mouse thyroid cells, Tubb1 expression in endothelial cells (Pecam-positive cells), epithelial cells (Epcam), fibroblasts (Pdgfra), and leucocytes (CD45) at E17.5 and adulthood: quantitative PCR results (normalized to Epcam-positive cells at adult stage and peptidylprolyl isomerase A). Mean±SEM of three independent cell-sorting experiments. Statistical comparisons versus epithelial cells (in black) at each stage, *p<0.05 using ANOVA test",
    "ncbi_link": "peptidylprolyl isomerase A: 
Tubb1: 545486"
  },
  {
    "caption": "F) Localization of transfected Myc-tagged wild-type and mutant (P160L) β1-tubulin in Nthy cells. Immunostaining with anti-Myc antibody (in green) and microtubule cytoskeleton stained with α-tubulin antibody (in red). Note that β1-tubulin -P160L is found throughout the cytoplasm showing puncta appearance, whereas wild-type β1-tubulin colocalizes with the microtubules",
    "ncbi_link": "Myc: 
β1-tubulin: 81027"
  },
  {
    "caption": "A) Thyroid morphology was investigated using Nkx2-1 staining at E9.5 and E11.5 (sagittal sections) and at E13.5, E15.5, and E17.5 (transverse sections) in wild-type (wt) and Tubb1-/- littermates. Nkx2-1was used as a marker of early thyrocyte progenitors and differentiated thyrocytes. Delays in thyroid migration and in fusion of the median anlage to the ultimobranchial bodies were observed at E11.5 and E13.5 (arrow), respectively, in Tubb1-/- mice. At E11.5, stained migrating thyroid cells were visible along the tract only in Tubb1-/- littermates (arrow). At E17.5, a pyramidal lobe was visible in Tubb1-/- littermates (arrow). tr: trachea; ub: ultimobranchial body. Scale bar: 50 μ",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "B) Total thyroid surface area (μm2) was quantified using Nkx2-1 staining at each embryonic stage. Top: thyroid surface area normalised for weight of each embryo. Bottom: thyroid surface area in μm2. Right: proliferation ratio calculated as the proportion of Nkx2-1-positive cells labelled with Ki67 at E9.5 in wt and Tubb1-/- thyroid anlages. ma: median anlage. Note that the thyroid ma is larger and the proliferation ratio higher at E.9.5 in Tubb1-/- mice, whereas from E13.5 onwards the Tubb1-/- thyroids were hypoplastic. Wt in black, KO, Tubb1-/- in gre",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "C) Thyroid marker expression by quantitative PCR in thyroid tissue at E15.5 and E17.5 in Tubb1-/- versus wt mice normalised for peptidylprolyl isomerase A. Note the decreases in thyroid differentiation markers at E15.5 and E17.5 and also in thyroid transcription factors at E17.5",
    "ncbi_link": "peptidylprolyl isomerase A: 
Tubb1: 545486"
  },
  {
    "caption": "D) Staining of Nkx2-1 and T4 at E17.5 and surface area quantification demonstrating T4 retention in Tubb1-/- versus wt thyroids. The data are the percentage of T4 or calcitonin (CT) surface area versus total thyroid area (estimated from the Nkx2-1-stained surface area). Scale bar: 50 μm. Student"s test, *p<0.05, **p<0.01 and ***p<0.001. Experiments were done on at least three tissues per stage for each gen",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "A) Serum TSH and T4 levels in 3-month-old Tubb1-/- and wild-type mice. Numbers of animals tested were 10 wild-type males and 14 Tubb1-/- males for TSH and for 14 wild-type and 22 Tubb1-/-males for T4. Tubb1-/- mice had hypothyroidism with elevated TSH and decreased T4 versus wild-type mice. Student\"s test, ** p<",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "B) Nkx2-1 (in brown) immunostaining of adult thyroid tissue. Note the disorganisation of the thyroid tissue in Tubb1-/- versus wild-type mice",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "C) Ultrastructural alterations shown by electron microscopy in wild-type and Tubb1-/- thyroid tissues. In Tubb1-/- tissues, note the disorganisation of secretion vesicles (white asterisks) and rods of identical density to secretion vesicles (white arrow). The ER is considerably dilated in Tubb1-/- thyrocytes. Representative views. Scale bars at the bottom left for each view. Co: colloi",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "D) ER stress in Tubb1-/- thyroid tissue. Top: Chop and XBPs expression by quantitative PCR in adults, normalized to peptidylprolyl isomerase A. Experiments with at least three tissues per stage for each genotype; wt in black and Tubb1-/- in grey. Bottom: Chop and Actin protein expression by western blotting in three representative wild-type and Tubb1-/- mice. The Chop band quantification normalised for Actin confirms the increased Chop expression demonstrated by quantitative PCR in Tubb1-/- versus wild-type thyroids. All lanes are from the same blot, which was cut where indicated. Student"s test, *p<0.05 and ***p<",
    "ncbi_link": "peptidylprolyl isomerase A: 
Chop: 13198
Tubb1: 545486
XBPs: 22433"
  },
  {
    "caption": "E) Co-immunostaining of endoplasmic reticulum (ER) marker (KDEL, in red), thyroglobulin (Tg in green), and both merged (from left to right) in adult thyroid tissue. Note the thyrocyte disorganisation in Tubb1-/- mice",
    "ncbi_link": "Tubb1: 545486"
  },
  {
    "caption": "Depletion of RBM14 induces ectopic formation of centriolar protein complexesA-E Mitotic control U2OS cells or U2OS cells treated with RBM14 siRNA were stained with antibodies against centrin-2 (green) and C-Nap1 (magenta) (A), Centrobin (green) and C-Nap1 (magenta) (B), centrin-2 (green) and CPAP (magenta) (C), acetylated-tubulin (green) and CP110 (magenta) (D), and centrin-2 (green) and γ-tubulin (magenta) (E). DNA is shown in blue. Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm. Histograms on the right represent frequency of mitotic cells with excess foci of the indicated proteins at spindle poles in each condition. Values are mean percentages ± standard error of mean (SEM) from three independent experiments (n = 30 for each condition). *P < 0.05, **P < 0.01, n.s., not significant (one-tailed t-test). Note that we counted the number of C-Nap1 foci after anaphase in mitosis when C-Nap1 signals recover from the reduction in prometaphase.",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "A U2OS cells or U2OS cells expressing FLAG-RBM14 full length (FL, aa1-669), N-terminal fragment (RBM14[N], aa1-150) or C-terminal fragment (RBM14[C], aa151-669) and treated with control siRNA or siRNA against 3′ UTR targeting endogenous RBM14 were stained with antibodies against FLAG as well as centrin-2. Histograms represent frequency of mitotic cells with excess centrin foci at spindle poles in each condition. Values are mean percentages ± SEM from three independent samples (n = 30 for each condition). **P < 0.01, n.s., not significant (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "C, D Cytoplasmic RBM14 could suppress centriole amplification in HU-treated cells. (C) U2OS cells or U2OS cells expressing FLAG-RBM14 FL or [C] and treated with or without HU were stained with antibodies against centrin-2 (green) and FLAG (magenta). (D) U2OS cells or U2OS cells expressing FLAG-RBM14 FL, FLAG-RBM14-NES or GFP-RBM14-PACT and treated with or without HU were stained with antibodies against FLAG (magenta, left) or GFP (magenta, right) as well as centrin-2 (green). Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 10 μm. Histograms represent frequency of cells in interphase with excess centrin foci in each condition. The percentages of U2OS cells with centrosomal localization of the RBM14 full-length protein or mutants are shown below the immunofluorescence images. We counted only cells that had adequate intensity of FLAG or GFP signals and did not find any significant difference in the total expression levels of the exogenous RBM14 proteins. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). **P < 0.01 (one-tailed t-test). Please note that cytoplasmic expression levels of GFP-RBM14-PACT are less than those of FLAG-RBM14 FL (˜0.5-fold) or FLAG-RBM14-NES (˜0.7-fold).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "D Mitotic U2OS cells treated with control or RBM14 siRNA were stained with antibodies against centrin-2 (green) and STIL (magenta). Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm. Histograms represent frequency of mitotic cells with excess STIL foci co-localized with centrin foci. Values are mean percentages ± SEM from three independent samples (n = 30 for each condition). **P < 0.01 (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "F Interaction between STIL and GFP-CPAP in the presence of FLAG-RBM14 FL or fragments. U2OS cells expressing GFP-CPAP were transfected with empty vector as a control, FLAG-RBM14[N], FLAG-RBM14[C] or FLAG-RBM14 FL constructs, immunoprecipitated with STIL antibodies, and the resulting IPs were analyzed by Western blotting using STIL, CPAP or FLAG antibodies. Quantification of relative protein amounts of co-immunoprecipitated GFP-CPAP in each STIL-IP fraction, normalized with the amount of STIL precipitated, is shown below the panels. Means ± SEM were calculated from three independent experiments. **P < 0.01 (one-tailed t-test). Note that we did not find any significant effect of exogenous expression of RBM14 full-length protein or deletion mutants on the expression levels of GFP-CPAP or endogenous STIL proteins in this experiment.",
    "ncbi_link": "CPAP: 55835
RBM14: 10432"
  },
  {
    "caption": "G U2OS cells treated with the indicated siRNAs were stained with antibodies against centrin-2 (green) and C-Nap1 (magenta). Histograms represent frequency of mitotic cells with excess centrin foci at spindle poles in each condition. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). **P < 0.01 (one-tailed t-test). Representative mitotic cells treated with siRNAs against RBM14 alone, RBM14 + STIL or RBM14 + CPAP are shown below. Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm.",
    "ncbi_link": "CPAP: 55835
RBM14: 10432
STIL: 6491"
  },
  {
    "caption": "A U2OS cells treated with control siRNA, RBM14 siRNA alone or RBM14 + HsSAS-6 siRNAs were stained with antibodies against centrin-2 (green) and HsSAS-6 (magenta). DNA is shown in blue. Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm. Histograms represent frequency of mitotic cells with excess centrin foci in the indicated conditions. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). n.s., not significant (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432
SAS-6: 163786"
  },
  {
    "caption": "B Live imaging of cycling RBM14-depleted HeLa cells expressing GFP-centrin1 (green) and RFP-H2B (magenta). Insets show approximately 1.5-fold magnified images of fluorescent foci. Time is denoted in hh:min, and scale bar is 10 μm. Time zero corresponds to the onset of excess centrin foci formation. Quantification of the number and total signal intensity of centrin foci in HeLa cells treated with control or RBM14 siRNA over time. Means ± SEM are shown (n = 5).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "C Ectopic formation of centriolar intermediates likely occurs from late G1 to S phase. Time-lapse recording across the cell cycle of HeLa cells expressing GFP-centrin (green) and RFP-H2B (magenta) and treated with RBM14 siRNA. Time is denoted in hh:min, and scale bar is 10 μm. Time zero corresponds to the metaphase onset.",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "E Amorphous electron-dense structures containing microtubules are formed in RBM14-depleted cells (see also Supplementary Fig S5I). Electron micrographs from U2OS cells depleted of RBM14. Squares indicate the ectopic electron-dense structures, whereas circles indicate the pre-existing centrioles. Scale bar, 500 nm and 200 nm (magnified views). Average diameter of pre-existing centrioles and the amorphous electron-dense structures are 225 ± 8 nm (n = 10) and 130 + 11 nm (n = 16), respectively. Insets show magnified views of the squares. Note that microtubules (black arrowheads) are observed within the electron-dense structures (white arrowheads).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "G U2OS cells expressing GFP-CPAP (green) and treated with RBM14 siRNA were analyzed using CLEM. Separate z-plane images of the cell with GFP-CPAP foci and the threefold magnified images are aligned from bottom to top along z-axis (left LM panels). White broken lines represent cell shapes, and blue broken lines represent nuclear shapes. Corresponding regions of EM images are shown on the right. White squares (a-d) represent the region around GFP-CPAP foci. Note that other than pre-existing centrioles (a, 1-4), ectopic small CPAP foci are recognizable as amorphous electron-dense structures (b-d). One of pre-existing centrioles (1) is elongated because of exogenous GFP-CPAP expression. Scale bar, 10 μm (LM), 2 μm (EM, low magnified image), 500 nm [magnified images of (a) and (d)), 200 nm (magnified images of (b) and (c)].",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "B-E Control U2OS cells or U2OS cells treated with siRNA targeting RBM14 were cold-treated for 30 min, followed by 30-60 min incubation at 37°C and stained with antibodies against centrin (magenta in (B) and (D)) or γ-tubulin (magenta in (E)) as well as α-tubulin (green). DNA is shown in blue. Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm. Histograms represent the percentages of mitotic cells showing the indicated phenotype at each time point. Values are mean percentages ± standard error of mean (SEM) from three independent experiments (n = 30 for each condition). *P < 0.05, **P < 0.01 (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "A U2OS cells treated with RBM14 siRNA and stained with antibodies against centrin-2 (green) as well as HsSAS-6 (magenta). DNA is shown in blue. Insets show approximately twofold magnified views of fluorescent foci around the centrosome. Scale bar, 5 μm. Histograms represent the frequency of mitotic cells with the indicated phenotype. Values are mean percentages ± SEM from three independent experiments (n = 60 for each condition).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "B Control U2OS cells or U2OS cells treated with siRNA targeting RBM14 were stained with antibodies against HsSAS-6 as well as centrin-2. Immunofluorescence micrographs are shown in Supplementary Fig S6D. When we counted HsSAS-6 foci in this paper, we only counted cells before metaphase/anaphase transition considering the disappearance of HsSAS-6 from anaphase in mitosis. Histograms represent frequency of mitotic cells with excess foci of the indicated proteins at spindle poles. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). *P < 0.05 (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "D RBM14-depleted HeLa cells expressing GFP-centrin (green) were stained with antibodies against CP110 (magenta) and HsSAS-6 (blue). Scale bar, 1 μm. A representative stained procentriole-like structure as well as endogenous centrioles is shown together with a schematic. Histograms represent length between the centers of the foci of the indicated proteins. Values are mean percentages ± SEM from seven individual cells.",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "E, F Ectopic DsRed-centrin-2 foci in RBM14-depleted cells recruit HsSAS-6-GFP. (E) Live imaging of RBM14-depleted U2OS cells expressing HsSAS-6-GFP (green) and DsRed-centrin-2 (magenta). Time is denoted in hh:min, and scale bar is 10 μm. Time zero corresponds to the onset of recording. Pre-existing HsSAS-6-GFP foci (white arrowheads) and ectopic HsSAS-6-GFP focus (red arrowhead) were traced throughout the time-lapse recording. White broken lines represent cell shapes, and blue broken lines represent nuclear shapes. (F) Histograms represent the percentages of ectopic DsRed-centrin-2 foci with HsSAS-6-GFP recruitment (n = 69 foci for control, and n = 67 foci for RBM14 siRNA).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "G Histograms represent frequency of mitotic cells with excess foci of HsSAS-6 in the indicated conditions. In this experiment, cells were treated with double amount of RBM14 siRNA (20 pmol) compared to that in the other experiments. Values are mean percentages ± SEM from three independent experiments (n = 30 for each condition). *P < 0.05 (one-tailed t-test).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "H HeLa cells expressing GFP-centrin (green) and RFP-H2B (magenta) and treated with RBM14 siRNA were analyzed using Live CLEM. Pre-existing GFP-centrin foci (white arrowheads) and ectopic GFP-centrin foci (red arrowheads) were traced throughout the time-lapse recording. Z-stacked confocal images spanning the entire height of the cells (< 30 μm) are shown (upper panels). Time is denoted in hh:min. Time zero corresponds to the onset of ectopic formation of GFP-centrin foci. The cells fixed after live imaging were also analyzed for confirming the local correlation between LM and EM images (lower panels). Red square (ectopically formed GFP-centrin foci) represents the region corresponding to that of the EM images acquired from serial sections. Note that ectopic GFP-centrin foci that form a spindle pole include not only electron-dense structures (1, 3) but also a morphologically recognizable centriole-like structure (2). Scale bars, 10 μm (live imaging) and 500 nm (EM).",
    "ncbi_link": "RBM14: 10432"
  },
  {
    "caption": "(A) Growth assay of the indicated cells with and without doxycycline-inducible overexpression of PLK4. Experiments were performed in wild-type or SAS6 monoclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733
SAS6: 163786"
  },
  {
    "caption": "(G) Top: Graph showing the efficiency of frameshifting INDELs measured using TIDE. N.D. = Not determined. Data shown is from n = 1 biological replicate. Bottom: Graph showing the relative growth of doxycycline treated PLK4Dox cells expressing an sgRNA targeting the indicated genes. Each dot displays measurements from a single experiment. Experiments were performed in polyclonal knockout cells. Data acquired across n ≥ 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(H) Quantification of centrosome number in PLK4Dox cells expressing an sgRNA targeting the indicated genes. Experiments were performed in polyclonal knockout cells. Data acquired across n ≥ 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(D) Quantification of the fraction of cells with PIDD1 localized to the mature mother centriole in PLK4Dox cells expressing an sgRNA targeting the indicated genes. A dot displays measurements from each experiment. Experiments were performed in PLK4Dox polyclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(F) Graph showing the relative growth of doxycycline treated PLK4Dox cells that were knocked out for the indicated genes. Each dot displays measurements from a single experiment. Experiments were performed in PLK4Dox monoclonal knockout cells. Data acquired across n ≥ 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(G) Quantification of the fraction of cells with PIDD1 localized at the mature mother centriole. Experiments were performed in PLK4Dox monoclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(A) Quantification of the fraction of cells with ANKRD26 localized at the mature mother centriole. Experiments were performed in PLK4Dox monoclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(B-D) Representative images of WT or ANKRD26-/- PLK4Dox cells immunostained with the indicated antibodies. Scale bar = 5 µm.",
    "ncbi_link": "ANKRD26: 22852
PLK4: 10733"
  },
  {
    "caption": "(E) Quantification of the fraction of WT or ANKRD26-/- hTERT RPE1 cells with cilia. Each dot displays measurements from a single experiment. Data acquired across n = 5 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "ANKRD26: 22852"
  },
  {
    "caption": "(F) Growth assay of the indicated cells with and without doxycycline-inducible overexpression of PLK4. Experiments were performed in PLK4Dox monoclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(G) Quantification of centrosome number in PLK4Dox cells expressing an sgRNA targeting the indicated genes. Experiments were performed in PLK4Dox monoclonal knockout cells. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(H) Western blot showing expression of pro-CASP2 and P21 following treatment with dox for the specified number of days. Experiments were performed in PLK4Dox monoclonal knockout cells. (I) Quantification of pro-CASP2 levels following treatment with dox for the specified number of days. Experiments were performed in PLK4Dox monoclonal knockout cells. Each dot displays measurements from a single experiment. Data acquired across n = 6 biological replicates. Mean ± s.e.m. ",
    "ncbi_link": "PLK4: 10733"
  },
  {
    "caption": "(C) Western blot showing the expression of ANKRD26. Experiments were performed in monoclonal ANKRD26-/- PLK4Dox cells expressing the indicated ANKRD26 transgenes.",
    "ncbi_link": "ANKRD26: 22852
PLK4: 10733"
  },
  {
    "caption": "(D) Quantification of the fraction of cells with ANKRD26 (left) and PIDD1 (right) localized to the mature mother centriole in monoclonal ANKRD26-/- PLK4Dox cells expressing the indicated transgenes. Each dot displays measurements from a single experiment. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "ANKRD26: 22852
PLK4: 10733"
  },
  {
    "caption": "(E) Graph showing the relative growth of doxycycline-treated, monoclonal ANKRD26-/- PLK4Dox cells expressing the indicated ANKRD26 transgenes. Each dot displays measurements from a single experiment. Data acquired across n = 3 biological replicates. Mean ± s.e.m.",
    "ncbi_link": "ANKRD26: 22852
PLK4: 10733"
  },
  {
    "caption": "(F) Western blot showing expression of pro-CASP2 and P21 following treatment with dox for 4 days. Experiments were performed in monoclonal ANKRD26-/- PLK4Dox cells expressing the indicated transgenes.",
    "ncbi_link": "ANKRD26: 22852
PLK4: 10733"
  },
  {
    "caption": "B Volcano plot showing proteins enrichment (fold change in log10 scale) after affinity purification in Jurkat T cells expressing ARHGAP45OST molecules compared to affinity purification in control Jurkat T cells expressing similar levels of WT (untagged) ARHGAP45 proteins prior to (unstimulated) and at 120 s after (stimulated) TCR stimulation. ARHGAP45 interacting proteins with a greater than 2-fold enrichment and a p-value < 0.01 were selected as specific ARHGAP45 interactors (Dataset EV1) and some of them are specified in red. Red lines represent the thresholds set on P-value and enrichment to identify specific ARHGAP45 interactors.",
    "ncbi_link": "ARHGAP45: 23526"
  },
  {
    "caption": "B The ratio of CTV/CMTPX-labeled cells present in each organ (Ro) was determined and normalized by dividing it with Ri, the ratio of CTV/CMTPX-labeled cells present in the cell mixtures prior to injection. Ro/Ri ratio corresponding to each of the specified mice are shown. Data shown for Arhgap45-/-mice correspond to 4 independent experiments (E1 to E4) involving a total of 15 individual mice whereas data shown for WT mice correspond to 2 independent experiments (E1 and E2) involving a total of 5 individual mice. The Arhgap45-/- mice analyzed on the same day as the control mice corresponded to the E1 and E2 experiments. Mean and SD are shown. ns, non-significant, **** P ≤ 0.0001; multiple unpaired T tests.",
    "ncbi_link": "Arhgap45: 70719"
  },
  {
    "caption": "C Expression of CCR7, and LFA-1 on naïve CD4+ and CD8+ T cells found in LNs of WT and Arhgap45-/- mice, analyzed by flow cytometry. Gray shaded curves, isotype control staining. D Quantification of data shown in (C). The MFI corresponding to each analyzed mouse is shown together with mean and SD. Each dot represents an individual mouse and CD4+ T cells from at least 4 mice have been analyzed for each condition. Mice analyzed on the same day are represented by similar dots (see key in bottom right corner). ns, non-significant, ** P ≤ 0.002; multiple unpaired T tests.",
    "ncbi_link": "Arhgap45: 70719"
  },
  {
    "caption": "The cells specified below were loaded into the upper chamber of a Transwell migration device without (no) or with the specified chemokines in the lower chamber. The percentage of cells that migrated to the bottom chamber after 2 h (T cells) or 4 h (B cells) is shown. A Chemotaxis of naïve CD4+ T cells from WT and Arghap45−/− mice in response to CCL19, CCL21 and CXCL12. B Chemotaxis of naïve CD8+ T cells from WT and Arghap45−/− mice in response to CCL19, CCL21 and CXCL12. C Chemotaxis of naïve B cells from WT and Arghap45−/− mice in response to CCL19 ",
    "ncbi_link": "Arghap45: 70719"
  },
  {
    "caption": "D Adding CCL19 in both the upper and lower chambers (CCL19 UL) prevented migration of WT and Arghap45−/− naïve T cells whereas the use of Transwell membrane inserts precoated with ICAM-1 (CCL19 + ICAM-1) did not change the pattern of chemotaxis observed using 'bare' membrane inserts (CCL19). E Chemotaxis of naive CD4+ T cells and B cells from WT, Arghap45−/−, and Arhgap45∆T/∆T mice in response to CCL19. F Chemotaxis of activated CD4+ T cells from WT and Arghap45−/− mice in response to CCL19. Data information: In (A) to (F) each dot represents an individual mouse and as shown CD4+ T cells from 3 to 9 mice have been analyzed for each condition. Mice analyzed on the same day are represented by similar dots (see key in bottom right corner). Mean and SD are shown. *P ≤ 0.033, ** P ≤ 0.002, *** P ≤ 0.001, **** P ≤ 0.0001; A, B, C, D, F multiple unpaired T test; E two-way ANOVA test. ",
    "ncbi_link": "Arghap45: 70719
Arhgap45: 70719"
  },
  {
    "caption": "Analysis of migration patterns of WT and Arghap45−/− activated T cells on 2D surface coated with ICAM-1. Each track represents the migratory path of individual WT and Arghap45−/− activated T cells recorded over 466 s in a single field of view, Trajectories were plotted to a common starting point, and > 200 T cells were recorded per plot using time-lapse microscopy at 10 x magnification. Analysis of migration patterns of WT and Arghap45−/− naive T cells on 2D surface coated with ICAM-1 and CCL21. Same conditions as in (A).",
    "ncbi_link": "Arghap45: 70719"
  },
  {
    "caption": "A, B Representative kymographs of WT (A) and Arghap45−/− (B) naive CD4+ T cells on 2D surface coated with ICAM-1 and CCL21.",
    "ncbi_link": "Arghap45: 70719"
  },
  {
    "caption": "A Irradiated H-2 Kb- positive spleen cells isolated from T cell-deficient mice were pulsed for 2 hours with the N4 agonist OVA peptide and cultured with CD8+ T cells purified from WT OT-I (WT) or Arhgap45−/− OT-I (Arhgap45−/−) mice. Cell proliferation was measured by luminescence after 48 h. Data are representative of 2 independent experiments with 3 mice per genotype (mean and SEM of triplicate are shown).",
    "ncbi_link": "Arhgap45: 70719
Arhgap45: 23526
H-2 K: 14964"
  },
  {
    "caption": "E. Double  immunofluorescent staining of Fn12230, fadA-deletion mutant US1  (∆fadA) and spontaneous mutant  lam in log and stationary phases using mAb 7H7 at 1:800 dilution and anti-human β-amyloid polyclonal antibody A11 at 1:500 dilution, followed by incubation with Alexa Fluor 680-conjugated donkey anti-rabbit  and Alexa Fluor 555-conjugated goat anti-mouse, both at 1:1,000 dilution. Co-staining of FadA and A11 was observed in Fn in  stationary phase, not in log phase, or in US1  or lam. The imagines were taken under 60X objective. Scale bar equals 5 μm.",
    "ncbi_link": "fadA: 45633877"
  },
  {
    "caption": "F. Scanning electron microscopy  of Fn 12230, US1 (∆fadA) and lam in log and  stationary phase at 10,000x magnification. Note the fibrous structure coating  Fn in stationary  phase, pointed by the clear arrows, but not in log phase. Scale bar equals 1 μm.",
    "ncbi_link": "fadA: 45633877"
  },
  {
    "caption": "G. Analysis of amyloid-like  FadA  produced by  Fn 23726 and its ∆fap2  mutant. An aliquot of 50 μg detergent-resistant pellets was loaded onto each lane, followed by SDD-AGE and Western blot analysis as described above. The mutant produced significantly less  amyloid-like polymers than the wild type.",
    "ncbi_link": "fap2: "
  },
  {
    "caption": "D. Effects of Congo Red on Fn survival in acidic environment. Wild type Fn 12230 (Fn) or its fadA deletion mutant US1 (∆fadA) grown to stationary phase were washed and incubated in PBS at pH4 in the presence of absence of 50 μg/ml Congo Red (CR) for 1 or 2 hours. The live bacterial counts   at time 0 were designated as 100%, and those after 1 or 2 hrs of incubation were expressed relative to  time 0. The results shown are the average of 5 independent experiments, each performed in duplicate. The error bars indicate SD. *p<0.05, ** p<0.01, ***p<0.001 (One-way ANOVA).",
    "ncbi_link": "fadA: 45633877"
  },
  {
    "caption": "F. Inhibition of  Fn attachment by FadAc in the presence or absence of anti-amyloid antibody  OC. An aliquot of 50 μg purified recombinant FadAc was pre-incubated with  DLD1 for 45 min either alone, or mixed with 20 μl  OC or rabbit IgG control, before Fn was added and the attachment assay performed as above. The attachment value by Fn alone was designated as 100%, with all other values expressed relative to it. FadA mutant L14A was included as a negative control. Data shown are mean values ± SEM. The experiment was performed in duplicate and repeated three times. **p< 0.01 (One-way ANOVA).",
    "ncbi_link": "FadA: 45633877
FadAc: 45633877"
  },
  {
    "caption": "D. Effect of detergent-resistant pellets prepared from Fn 12230 (Fn) and US1 (∆fadA) on tumor growth. HCT116 cells were inoculated into the nude mice as described above. In one group of mice (n=3), sarkosyl-resistant pellets prepared from  Fn 12230 and US1 (∆fadA) were injected into the tumors on opposite sides. In another group (n=5), sarkosyl-resistant pellets prepared from Fn 12230 were mixed with OC  or rabbit IgG control (rIgG) before injecting into the tumors on opposite sides. The tumor volumes were measured described above. The vertical lines represent the standard deviations. The individual tumor pairs are shown (right panel). *p < 0.05, **p < 0.01, ***p< 0.001 [compared to US1 (∆fadA), t-test].",
    "ncbi_link": "fadA: 45633877"
  },
  {
    "caption": "A. Approximately 1x109 CFU of  Fn 12230, US1 (∆fadA), and lam suspended in carboxymethylcellulose (CMC) were orally administered to C57BL/6 mice three times a week for 10 weeks. CMC alone was administered as a control. Maxillae from mice inoculated with CMC  alone (n=5),  Fn 12230 (n=5), US1 (∆fadA; n=5), and lam (n=4) were harvested and fixed in 4% paraformaldehyde  and stored in 70% ethanol, followed by microCT (μCT) scanning using a Scanco vivaCT 80 system at 55 kVp, 145 µA, and 250 ms integration time. Shown in the figure are reconstructed grayscale  images. ImageJ was used to measure difference in bone height from the cementoenamel junction (CEJ) to the alveolar crest  between palatal roots of first  and second molars (see arrows). B. The average bone loss of each group shown in (A), with the lines above each bar representing standard deviations. *p< 0.05. **p< 0.01 (t-test). ",
    "ncbi_link": "fadA: 45633877"
  },
  {
    "caption": "D qRT-PCR analysis of FN1, Collagen I and Collagen III in WT and cKI mice after 5/6Nx (n=6 in cKI+Sham group, n=5 in the other three groups, biological replicates)",
    "ncbi_link": "Collagen I: 12842
Collagen III: 12825
FN1: 14268"
  },
  {
    "caption": "H qRT-PCR analysis of FN1, Collagen I, Collagen III and α-SMA in WT and cKO mice after 5/6Nx (n=5 in WT+Sham group, n=7 in cKO+Sham group, n=6 in 5/6Nx groups, biological replicates).",
    "ncbi_link": "α-SMA: 11475
Collagen I: 12842
Collagen III: 12825
FN1: 14268"
  },
  {
    "caption": "D qRT-PCR analysis of FN1, Collagen I, Collagen III, Collagen IV, α-SMA and Vimentin (n=3, biological replicates).",
    "ncbi_link": "α-SMA: 59
Collagen I: 1277
Collagen III: 1281
Collagen IV: 1282
FN1: 2335
Vimentin: 7431"
  },
  {
    "caption": "western blotting analysis of Hmgcs2 expression in WT and Hmgcs2+/- mice (n=3, biological replicates).",
    "ncbi_link": "Hmgcs2: 15360"
  },
  {
    "caption": "J-N Representative Western blot and densitometric analysis of LONP1, FN1, α-SMA and Vimentin of each group was shown. Three independent experiments were carried out and quantification of the abundance of these proteins is shown in panel (n=3 in each group). mPTCs were transfected with siNC or siLONP1, and then pre-treated with 84-B10 (10 μM) 2h before TGF-β1 (10ng/mL) treatment for another 24h.",
    "ncbi_link": "LONP1: 74142"
  },
  {
    "caption": "Bar graph represents IL-2 secretion by NKT cell hybridoma (2C12) co-cultured murine macrophage cell line (J774.2) treated either with thapsigargin- or tunicamycin-treated CD1d knockdown (white bars) or untransfected (black bars). Knockdown of CD1d blocked IL-2 secretion by 2C12. In total, n=2 biological replicates were performed (three technical replicates per biological replicate). Graphs show mean ± SEM of each biological replicate.",
    "ncbi_link": "CD1d: 12480///12479"
  },
  {
    "caption": "Bar graph represents IL-2 secretion by NKT cell hybridoma (2C12) co-cultured either with thapsigargin- or tunicamycin-treated primary BMDM isolated from CD1d-/- (white bars) or wild type (black bars) mice. 2C12 cocultured with CD1d-/- BMDMs resulted in reduced IL-2 secretion. Graphs show mean ± SEM from n=3 biological replicates. ***P < 0.001 (Unpaired t test).",
    "ncbi_link": "CD1d: 12480///12479"
  },
  {
    "caption": "Immunoblots represents the knockdown efficiency for IRE1α and PERK protein in J774.2 cell line transduced with lentiviral particles carrying gRNA against the IRE1α or PERK gene.",
    "ncbi_link": "PERK: 13666
IRE1α: 78943"
  },
  {
    "caption": "Bar graph represents percentage of IL-2 secretion by NKT cell hybridoma (2C12) co-cultured with thapsigargin-treated murine IRE1α or PERK knockdown macrophage cell line (J774.2). Knockdown of IRE1α (black bar) or PERK (grey bar) resulted in significant reduction in IL-2 secretion by iNKT hybridoma. In total n=2 biological replicates were performed (three technical replicates per biological replicate). Graphs show mean ± SEM of each biological replicate.",
    "ncbi_link": "PERK: 13666
IRE1α: 78943"
  },
  {
    "caption": "Bar graph represents that recycling of CD1d between various endomembrane compartments and the cell surface is required for optimal IL-2 secretion by NKT cells. In total, n=2 biological replicates were performed (three technical replicates per biological replicate). Graphs show mean ± SEM of each biological replicate.",
    "ncbi_link": "CD1d: 12479///12480"
  },
  {
    "caption": "Western blotting analysis of Gadd45a protein expression in mouse intestine crypt lysates from WT and G3Terc-/- mice (A). Quantification of Gadd45a protein expression, β-actin protein level was used as the loading control (n=7 mice per genotype), two independent experiments were carried out (B).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Quantification of Gadd45a-ChIP values as percentage of total telomeric DNA and ALU elements in WT and G3Terc-/- MEF cells (n=3 for each genotype).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Dot-bot assay following Gadd45a-ChIP in WT and G3Terc-/- MEF cells.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Kaplan-Meier survival curves of the mice with indicated genotypes (WT, n=44; Gadd45a-/-, n=48; G3Terc-/-, n=37; G3-dKO, n=41). P value comparing the survival of G3Terc-/- with G3-dKO mice is calculated with the log-rank test.",
    "ncbi_link": "Gadd45a: 13197
Terc: 21748"
  },
  {
    "caption": "The average body weight of mice with indicated genotypes at indicated time points (G3-dKO Female (n=19) vs G3Terc-/- Female (n=17), P=0.004; G3-dKO Male (n=14) vs G3Terc-/- Male (n=14), P=0.0038). P values are calculated with log-rank test.",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Representative images of γH2AX antibody staining on small intestine paraffin sections from WT, Gadd45a-/-, G3Terc-/-, and G3-dKO mice (7 months old). Arrows indicate γH2AX positive nuclei (C). Quantification of the percentage of γH2AX positive cells per small intestine crypt (n=4-6 mice per group) (D).",
    "ncbi_link": "Gadd45a: 13197
Terc: 21748"
  },
  {
    "caption": "Representative image of the anaphase bridge (indicated with arrows) in the basal crypt of G3Terc-/- mice (G). The percentage of cells with anaphase bridges in pH3 positive basal crypt cell population (n=4-6 mice per genotype) (H).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Representative images of small intestine organoids from WT and G3Terc-/- mice incubated with or without APE1 inhibitor (CRT0044876, 10μM) treatment. Arrows indicate the crypt-like structure in organoid cultures (A). Quantification of organoid number (per well) and size (in 104 μm2) (n=3-4 mice per genotype/treatment) (B-C).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "Representative images of γH2AX antibody staining on dissociated organoid cells from WT and G3Terc-/- organoid cultures with or without APE1 inhibitor (CRT0044876, 10μM) (DNAs are stained with DAPI) (D). Quantification of γH2AX positive cells (n=3-4 mice per group) (E).",
    "ncbi_link": "Terc: 21748"
  },
  {
    "caption": "The knockdown efficiency of shRNA-GADD45A in human WI38 fibroblasts.",
    "ncbi_link": "GADD45A: 1647"
  },
  {
    "caption": "The proliferation curves of human WI38 fibroblasts treated with control shRNA or shRNA against GADD45A.",
    "ncbi_link": "GADD45A: 1647"
  },
  {
    "caption": "Representative images of β-gal staining in human fibroblast cultures with control and shRNA-GADD45A treatments at passage 54 (C). Quantification of the percentage of β-gal positive cells in human fibroblasts with control and shRNA-GADD45A treatments (duplicates per group) (D).",
    "ncbi_link": "GADD45A: 1647"
  },
  {
    "caption": "D Yeast two-hybrid analysis shows the effect of deletion of the amino acids 384-522 of MMS22L on the interaction with RPA. The interaction between indicated MMS22L variants fused to LexA DNA-binding domain and RPA1 fused to GAL4 activating domain (GAD) is assessed by survival on media containing 3-aminotriazole (3-AT) in the absence of histidine and by β-galactosidase activity (X-Gal) assays.",
    "ncbi_link": "MMS22L: 253714"
  },
  {
    "caption": "E Images of MMS22L foci formed in U2OS cells stably expressing wild-type (WT) or Δ384-522 variants of siRNA-resistant HSS-MMS22L, depleted of endogenous MMS22L by RNAi and treated with 50 nM CPT for 18 hours. Scale bar: 5 μm.",
    "ncbi_link": "MMS22L: 253714"
  },
  {
    "caption": "A Representative immunofluorescence images of foci induced by short CPT treatment (50 nM, 1 h) in U2OS cells treated with indicated siRNAs showing the effect of MMS22L depletion on the RAD51 foci. Scale bar: 5 μm.B Boxplot quantification of representative experiment in (A) (n = 3; nnuclei ≥ 78). Boxes indicate the 25-75 percentile and whiskers the 10-90 percentile; horizontal lines mark \u2028the medians. Nuclei with ≥ 25 γH2AX foci (marker of replication stress sites) were analyzed. Statistical analysis: Mann-Whitney U test; *** P ≤ 0.0001.",
    "ncbi_link": "MMS22L: 253714"
  },
  {
    "caption": "H Representative immunofluorescence images of CPT-induced foci in stable U2OS cell lines depleted of endogenous MMS22L and overexpressing indicated siRNA-resistant variants of HSS-MMS22L treated with 50 nM CPT for 1 hour. Scale bar: 5 μm.",
    "ncbi_link": "MMS22L: 253714"
  },
  {
    "caption": "I-K Quantification of the effect of indicated MMS22L mutations on RAD51 foci in U2OS cells treated with 50 nM CPT for 1 h (I; n = 3), 50 nM CPT for 18 h (J; n = 3) or 5 µM ETP for 1 h followed by 3 hours incubation without the drug (K; n = 3). Graphs represent averaged median values; error bars indicate SEM. Statistical analysis according to one-way ANOVA with Bonferroni post-test; *** P ≤ 0.001; ** P ≤ 0. 01; ns, not significant. Representative immunofluorescence images are shown in (H), Figures EV6G and EV6H, respectively.",
    "ncbi_link": "MMS22L: 253714"
  },
  {
    "caption": "(a) Structure of the GBA1 gene on chromosome 1 and schematic overview of gene correction using ZFNs. Black boxes represent exons. (b) Mutated and gene-corrected (GC) iPSCs after sequencing (upper lanes: iPSCs with heterozygous mutations; lower lanes: iPSCs with homozygous wt-GBA1 sequences as indicated by arrows).",
    "ncbi_link": "GBA1: 2629"
  },
  {
    "caption": "(b,c) Immunocytochemistry at DIV2 post-sort for TH (green) and the neuronal marker MAP2 (red) performed on the neuronal (b) and mixed (c) populations of a representative control and GBA-PD line. Nuclei were counterstained with Hoechst (blue). FACS enriches for both TH and neuronal marker positivity in the neuronal population compared with the non-neuronal population. (Bars, 50 μm.)",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(a) Ganglioside composition of human fibroblasts, iPSCs, differentiated iPSCs and enriched iPSC-derived neurons (after FACS) from control (line C1-1), GBA-PD (line PD1-1) and GD (line GD1-1) subjects. Cell lipids were metabolically labelled with [1-3H]sphingosine and visualized by digital autoradiography.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "c) GBA1, GBA2, β-galactosidase and HEXA and HEXB gene expression levels in control iPSCs and iPSC-derived enriched neurons at DIV65. Data are represented as mean+s.d.; experiments were independently repeated three times in triplicate. *P0.05; **P0.01, Student's t-test.",
    "ncbi_link": "GBA1: 2629
GBA2: 57704
β-galactosidase: 2720
HEXA: 3073
HEXB: 3074"
  },
  {
    "caption": "(a) LC-MS/MS analysis showing the level of Glc-Cer in control, GBA-PD, isogenic controls and GD iPSC-derived neurons. Data are represented as mean+s.d.; n=3, *P0.01, One-way ANOVA.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(c,d) Representative western blots showing the protein levels of α-syn in control, GBA-PD, gene-corrected isogenic controls and GD iPSC-derived neurons.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(c,d) Representative western blots showing the protein levels of α-syn in control, GBA-PD, gene-corrected isogenic controls and GD iPSC-derived neurons.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(a) Glycohydrolase enzyme activities (GCase, GBA2, β-galactosidase, β-hexosaminidase) were measured in enriched neurons from control, GBA-PD, isogenic gene-corrected control and GD iPSC-derived neurons at DIV65. Enzyme activities are expressed as pmoles mg−1 h−1. Data are represented as mean+s.d.; experiments were independently repeated three times in triplicate. *P0.05; **P0.01; ***P0.001 compared with controls, one-way ANOVA.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(b,c) Representative western blots of GCase protein levels in control, GBA-PD, corresponding gene-corrected and GD iPSC-derived neurons. Data are represented as mean+s.d.; experiments were independently repeated three times. *P0.05; **P0.01, one-way ANOVA and Student's t-test.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "CSF glycohydrolase activities were measured in patients with idiopathic PD (iPD), GBA-PD patients and age-matched unaffected individuals (CTRL). Enzyme activities were normalized to total protein concentrations and expressed as pmoles mg−1 h−1. Data are represented as mean+s.e.m.; CTRL, n=14; iPD, n=15; GBA-PD, n=15. Experiments were performed in triplicate. *P0.05; **P0.01, Mann-Whitney U test.",
    "ncbi_link": "GBA: 2629"
  },
  {
    "caption": "(e) Knockdown efficiency of NECAB2 determined by qRT-PCR and normalized to scrambled non-targeting shRNA. Data are represented as mean+s.d.; experiments were independently repeated three times in triplicate. ***P0.0001, Student's t-test.",
    "ncbi_link": "NECAB2: 54550"
  },
  {
    "caption": "(f) Representative western blot for NECAB2 showing knockdown efficiency. 1, scrambled non-targeting shRNA; 2, NECAB2 shRNA.",
    "ncbi_link": "NECAB2: 54550"
  },
  {
    "caption": "(g) Quantification of TH+ cells in GBA-PD and GD iPSC-derived neuronal cultures infected with scrambled non-targeting shRNA or NECAB2 shRNA lentivirus and treated with A23187 (1 μM for 4 h). Values were calculated as a percentage of scrambled shRNA-treated cells. Data are represented as mean+s.e.m.; experiments were independently repeated three times in triplicate. *P0.01, Student's t-test.",
    "ncbi_link": "GBA: 2629
NECAB2: 54550"
  },
  {
    "caption": "(h) Representative images showing GBA-PD iPSC-derived DA neurons infected with scrambled non-targeting shRNA or NECAB2 shRNA lentivirus and treated with A23187 (1 μM for 4 h). Cells were stained for β-TubIII (green) and TH (red). Nuclei were counterstained with Hoechst (blue). (Bar, 20 μm.)",
    "ncbi_link": "GBA: 2629
NECAB2: 54550"
  },
  {
    "caption": "(F) ChIP-seq tracks Brd4 on select genes (Foxp3, Nr4a2, Med1, Taf10, Ar, and Fbxw7) in Th2 cells, treated with or without JQ1.",
    "ncbi_link": "Ar: 11835
Fbxw7: 50754
Foxp3: 20371
Med1: 19014
Nr4a2: 18227
Taf10: 24075"
  },
  {
    "caption": "(B) qPCR analysis of Il4, Il5, Il13, Gata3, Foxp3 and Fbxw7 in mouse Th2 cells infected with sh-Ctrl, sh-Foxp3, and sh-Fbxw7 lenti-virus.",
    "ncbi_link": "Fbxw7: 50754
Foxp3: 20371
Gata3: 14462
Il13: 16163
Il4: 16189
Il5: 16191"
  },
  {
    "caption": "(C) Immunoprecipitation of Flag-tagged Fbxw7 with anti-Flag affinity gel, followed by Western blotting of Myc to detect Myc-Gata3 in HEK293T cells transfected with Myc-Gata3 and/or Flag-Fbxw7 plasmids.",
    "ncbi_link": "Flag: 
Myc: 
Fbxw7: 50754
Gata3: 14462"
  },
  {
    "caption": "(C) ChIP-qPCR analysis of histone modifications on the gene loci of Foxp3 and Fbxw7 in mouse Th2 cells treated with or without JQ1 (250nM).",
    "ncbi_link": "Fbxw7: 50754
Foxp3: 20371"
  },
  {
    "caption": "(F) ChIP-qPCR analysis of Brd4, Ezh2, Suz12 and EED binding on the gene loci of Il4, Il5, Foxp3 and Fbxw7 in mouse Th2 cells treat with or without JQ1 (250nM).",
    "ncbi_link": "Fbxw7: 50754
Foxp3: 20371
Il4: 16189
Il5: 16191"
  },
  {
    "caption": "(B) HEK293T cells are transfected with Flag-Brd4 and HA-EED, HA-Ezh2, and Suz12 plasmids. Lysates are immunoprecipitated with Flag-tagged Brd4, treated in-vitro with JQ1 (5μM), MS402 (5μM), and ABBV-744 (5μM), followed by Western blotting of HA.",
    "ncbi_link": "Flag: 
HA: 
Brd4: 57261
EED: 13626
Ezh2: 14056
Suz12: 52615"
  },
  {
    "caption": "(F) HEK293T cells are transfected with Flag-Brd4, HA-EED and HA-EED(K19R) plasmids. Lysates are immunoprecipitated with Flag followed by Western blotting of HA, and vice versa.",
    "ncbi_link": "Flag: 
HA: 
Brd4: 57261
EED: 13626"
  },
  {
    "caption": "(B) qPCR analysis of Il4, Il5, Gata3 in mouse Th2 cells treated with ABBV-744 at 500nM and 1μM.",
    "ncbi_link": "Gata3: 14462
Il4: 16189
Il5: 16191"
  },
  {
    "caption": "(E) qPCR analysis of Foxp3 in mouse Th2 cells treated with ABBV-744 at 500nM and 1μM. (F) qPCR analysis of Fbxw7 in mouse Th2 cells treated with ABBV-744 at 500nM and 1μM. (",
    "ncbi_link": "Fbxw7: 50754
Foxp3: 20371"
  },
  {
    "caption": "A-B. Correlation of MCU and MCUb expression levels with breast cancer clinical stages. Median-centered log2 mRNA expression levels of MCU and MCUb were collected from the TCGA breast cancer dataset (http://tcga-data.nci.nih.gov/docs/publications/brca_2012/). Data were plotted and analysed against tumor size (T1-T4) (A) and regional lymph node infiltration (N0-N3) (B), according to the AJCC Cancer Staging Manual (7th edition). Linear regression analysis with different stages was implemented. Parameters of linear regression are shown. Number of samples for each stage are shown in parentheses.",
    "ncbi_link": "MCUb: 55013
MCU: 90550"
  },
  {
    "caption": "F-H. MCU silencing impairs TNBC cell migration. Cells were transfected with siMCU or siControl. The day after transfection, a linear scratch was obtained on the cell monolayer through a vertically held P200 tip (time- point 0h). Cell migration into the scratched area was monitored 48 hours later. The covered area was measured and expressed as a percentage relative to 0-hour time-point (n=12). P-value: ***p<0.0001.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "A. Re-expression of mMCU rescues cell motility of MCU-silenced cells. Cells were transfected with siMCU or siControl. Ad-mMCU was used to re-express MCU (Ad-GFP was used as control). MCU protein expression was verified by western blot. The day after transduction a linear scratch was made (time-point 0h). Cell migration into the wounded area was monitored at 48 hour time-point and the covered area was measured (n=12). P-value: ***p<0.0001.",
    "ncbi_link": "MCU: 90550
MCU: 215999"
  },
  {
    "caption": "B. MCU silencing blunts cell invasiveness. Stable shMCU and shControl-expressing spheroids were plated and let grow into collagen-I (0 hour time-point). Spheroid area was measured at 0-hour and 48-hour (n=8). Scale bar 300 μm. P-value: ***p=0.0003.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "C. MCU silencing reduces the clonogenic potential of MDA-MB-231 cells. Stable shMCU and shControl-expressing cells were plated at low confluence (2x103/well of a 6-well plate). After 7 days the number of colonies was counted (minimum 30 cells/colony, n=8). P-value: **p=0.0027.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "D. MCU depletion does not induce cell death. Cells were transfected with siMCU or siControl. 72 hours later, cell apoptosis and necrosis were measured by FITC-Annexin V and Propidium Iodide (PI) detection (Q1: PI positive, Q2: PI and FITC-Annexin V positive, Q3: PI and FITC-Annexin V negative, Q4: FITC-Annexin V positive. n=6).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "E. MCU depletion does not alter cell cycle. Cells were transfected with siMCU or siControl. 72 hours later, cell cycle distribution was monitored by Propidium Iodide (PI) detection (n=6).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "A. Tumor mass volume was measured at specific time-points until the day of sacrifice (day 39 post-injection for control, day 46 and 56 p.i. for MCU-/- cl.1 and cl.2, respectively). P-values: ***p=0.0001, ***p<0.0001.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "A-C. FLIM analysis of cellular NADH/NADPH levels. Fluorescence lifetimes of NAD(P)H autofluorescence in stable shControl and shMCU expressing cells were imaged. Representative images of the distribution of τbound on an intensity weighted pseudocolored scale (2.2-2.5 ns) are shown. Scale bars = 20 μm (A). Mean +/- SE of τbound (B) and relative NADH and NADPH intensities (C) calculated from equation in (Blacker et al., 2014) are shown (n=3). P-values: **p=0.01, **p=0.002, respectively.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "F. MCU depletion impairs the mitochondrial rate of ATP production. Cells were transfected with siMCU or siControl. 48 hours later, cells were treated with 5.5 mM 2-deoxy-D-glucose for 1 hour and cellular ATP levels were quantified (n=6). P-value: ***p=0.0009.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "C. MCU silencing does not affect matrix pH. Cell were transfected with siMCU or siControl and SypHer2 probe. 48 hours later, matrix pH was measured (n=22).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "D-E. Mitochondrial H2O2 levels are critically blunted after MCU depletion. Cells were transfected with shMCU or shControl, together with the ratiometric YFP-based biosensor pHyper-dMito (D) or the mitochondrial H2O2-sensitive HyPerRed probe (E). 48 hours later, H2O2 production was measured (n=35). P-values: *p=0.02, *p=0.05, respectively.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "F. Mitochondrial superoxide levels are critically blunted after MCU silencing. Cells were transfected with siMCU or siControl. 48 hours later, cells were loaded with the red dye MitoSOXTM and superoxide anion levels were measured (n=25). P-value: *p=0.04.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "G. Mitochondrial GSSG/GSH ratio is critically reduced after MCU silencing. Cells were transfected with shMCU or shControl, together with the mitochondrial targeted mitGrx1-roGFP2 probe. 96 hours later, the glutathione redox potential (EGSH) was measured (n=46). P-value: ***p<0.0001.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "A. MCU silencing reduces HIF-1α protein levels. Cells were transfected with siMCU or siControl. HIF-1α protein levels were detected 48 hours later.",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "B. MCU silencing reduces MG132-mediated HIF-1α and hydroxylated HIF-1α protein accumulation. Cells were transfected with siMCU or siControl. 48 hours later, cells were treated with 10 μM of the proteasome inhibitor MG132. Left: Protein levels were revealed by western blot. Right: quantification by densitometry (n=5).",
    "ncbi_link": "MCU: 90550"
  },
  {
    "caption": "C. ROS increase HIF-1α transcription. Cells were treated O/N with 100 µM paraquat to induce ROS production. HIF-1α mRNA levels were measured by RealTime-PCR (n=3). P-value: **p=0.002.",
    "ncbi_link": "HIF-1α: 3091"
  },
  {
    "caption": "D-J. MCU silencing reduces mRNA levels of HIF-1α, HIF-2α, and HIF-1α target genes. Cells were transfected with siMCU or siControl. mRNA expression was measured by RealTime-PCR (n=3). P-values: (HIF-1α) **p=0.0031, **p=0.009, (HIF-2α)**p=0.01, (LOX)***p=0.001, ***p=0.0005, (PDK1)*p=0.02, **p=0.009, (G6PI)*p=0.02, **p=0.005, (CA IX)**p=0.0026, **p=0.0022, (HK2) **p=0.0024, *p=0.03.",
    "ncbi_link": "CA IX: 768
HIF-2α: 2034
G6PI: 2821
HIF-1α: 3091
HK2: 3099
LOX: 4015
MCU: 90550
PDK1: 5163"
  },
  {
    "caption": "K. HIF-1α overexpression rescues siMCU-mediated migration impairment. Cells were transfected with siMCU or siControl. Wild type (wt) and constitutively active (ca) HIF-1α were expressed by retroviral infection (pBABE was used as control). The day after transduction, cells were scratched (time-point 0h). Cell migration into the wounded area was monitored at 48 hour time-point and the covered area was measured (n=12). P-values: ***p<0.0001, *p=0.04.",
    "ncbi_link": "HIF-1α: 3091
MCU: 90550"
  },
  {
    "caption": "L-M. MCU expression levels correlate with HIF1α (L) and HIF1α-regulated genes (M). A linear model (lm) to test the power of MCU expression levels predicting the expression of HIF1α and HIF1α-regulated genes was calculated and plotted for each of the 532 samples of the TCGA database (see Figure 1). Equation and R2 values of the linear regression and significance indicating deviation from 0 are shown. The area of 95% prediction limit is shaded below and above the linear regression line. The HIF1α-regulated gene set was compiled from Broad Institute GSEA database (http://www.broadinstitute.org/gsea/msigdb/cards/V$HIF1_Q5.html, merged sets of V$HIF1_Q3 and V$HIF1_Q5).",
    "ncbi_link": "HIF1α: 3091
MCU: 90550"
  },
  {
    "caption": "B HeLa cells expressing the indicated GFP-tagged Nups were semi-permeabilized and incubated with mitotic HeLa cell extract at 30ºC. NPC disassembly was followed by monitoring the fluorescence intensity of the respective Nups at the nuclear rim and influx of TRITC-dextran. Scale bar, 30 μm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "D, E Detection of FLAIL and asFLAIL gene expression in Col-0 and flail mutants by strand-specific RT-qPCR. Transcript levels were normalized to UBQ expression levels. Y-axis showed relative values compared to the expression level of Col-0.",
    "ncbi_link": "FLAIL: 
flail: 
UBQ: 830705"
  },
  {
    "caption": "B, C Detection of sense FLAIL and asFLAIL transcript expression in Col-0, flail3 mutant and complementation lines by strand-specific RT-qPCR. pFLAIL:gFLAIL18/88 and pasFLAIL:gasFLAIL18/39 represented sense and antisense FLAIL complementation lines, respectively with flail3 35S:GUS transgenic line as a control. Positions of primers used for strand-specific RT-qPCR analyses were the same as those in Figure 1A. Transcript levels were normalized to UBQ expression levels. Y-axis showed relative values compared to the expression level of Col-0.",
    "ncbi_link": "FLAIL: 
flail: 
GUS: 
UBQ: 830705"
  },
  {
    "caption": "D Representative morphological phenotypes of 4-week-old plants of Col-0, flail3 mutant, transgenic lines. Scale bar: 2 cm. E Violin graph showed number of rosette leaves after appearance of the first flower bud in Col-0.",
    "ncbi_link": "flail: "
  },
  {
    "caption": "A Heatmap of 13 flowering genes and sense FLAIL was cropped with systematic gene names illustrating that the expression of dysregulated flowering genes in flail3 was fully (AGL24, CO, COOLAIR, CIR1, FBH4, LAC8, PLL25, PRE1) or partially (AGL20, DDF1, MAF4, NMT3, PHYA) rescued in complementation line. DEGs analyzed by DESeq2 with |log2 fold change| > 1 and adjusted p value < 0.05 were considered significant differential expression. Three biological replicates for Col-0, flail3, and two for flail3 pFLAIL:gFLAIL18 (complement). Flowering genes were highlighted in red. The color scale reflected the log 2-fold change in gene expression, ranging from down-regulated (blue) to up-regulated (red).",
    "ncbi_link": "FLAIL: 
flail: 
AGL20: 819174
AGL24: 828556
NMT3: 843694
PLL25: 827005
COOLAIR: 28720403
CO: 831441
DDF1: 837817
FBH4: 818829
LAC8: 831877
MAF4: 836631
PHYA: 837483
PRE1: 833982
CIR1: 833700"
  },
  {
    "caption": "Genome browser screenshots illustrating the expression of sense FLAIL and dysregulated flowering genes in flail3 were rescued in complementation line (top panel). Normalized read counts (TPM from RNA-seq) for differentially expressed flowering genes in Col-0, flail3, and flail3 pFLAIL:gFLAIL18 plants (bottom panel).",
    "ncbi_link": "FLAIL: 
flail: "
  },
  {
    "caption": "E, F Genome browser screenshots illustrating two of FLAIL bound targets CIR1 (E) and LAC8 (F) in ChIRP-seq.",
    "ncbi_link": "FLAIL: 
LAC8: 831877
CIR1: 833700"
  },
  {
    "caption": "FLAIL affects AS of LAC8. Light blue arrows indicate probes used for gel electrophoresis in C; LAC8 isoforms were detected by RT-PCR with black arrow indicating LAC8.1, grey arrow indicating LAC8.2, and brown arrow indicating LAC8.3. -RT, negative control without adding reverse transcriptase. Isoform bands were quantified using Image Lab software relative to the respective UBQ band of each sample.",
    "ncbi_link": "FLAIL: 
UBQ: 830705
LAC8: 831877
LAC8.1: 831877
LAC8.2: 831877
LAC8.3: 831877"
  },
  {
    "caption": "F-H ChIRP-qPCR using probe pools FLAIL-asDNA (Odd and Even) identified FLAIL binding snRNAs U1, U2 and U5. Luc-asDNA probes retrieved RNAs as a negative control. Retrieved FLAIL transcript was served as a positive control; UBQ and a non-coding, unspliced, conserved snoRNA lncCOBRA1 (AT1G05913) as negative controls",
    "ncbi_link": "FLAIL: 
Luc: 
AT1G05913: 28716398
COBRA1: 28716398
UBQ: 830705
U5: 836235
U2: 829822
U1: 824230"
  },
  {
    "caption": "I Morphological phenotypes of 4-week-old plants of Col-0, flail3, lac8-52-34, lac8 flail3-55-1 mutants. Scale bar: 2 cm. J Violin graph showed number of rosette leaves after appearance of the first flower bud in Col-0. Data represented the mean of at least seven independent experiments in Col-0, flail3, lac8-52-34, lac8 flail3-55-1.",
    "ncbi_link": "flail: 
lac8: 831877"
  },
  {
    "caption": "Volcano plots of piliation, aggregation and adhesion mutation scores for all pilE mutations. Stop and synonymous mutations are highlighted in blue and orange respectively. Adhesion and aggregation mutation scores relative to piliation. The correlation appears as a red dotted line.",
    "ncbi_link": "pilE: "
  },
  {
    "caption": "Early adhesion of pilE mutants as a function of aggregation. Values were normalized to that of pilESB. Each dot represents a pilE mutant and the pilV, pilD, pilX and pilC1 reference mutants. Mutants in the region surrounding A131 are in green and those surrounding Y50 in purple. A blown-up view of the zone of interest (lower left quarter) is presented on the right panel. The shaded area highlights the absence of significant adhesion.",
    "ncbi_link": "pilE: "
  },
  {
    "caption": "Early adhesion of PilE mutants as a function of piliation per bacterium normalized to that of pilESB.",
    "ncbi_link": "PilE: "
  },
  {
    "caption": "C-terminally GFP-tagged NRC2EEE and C-terminally RFP-tagged Rx were co-expressed either with an EV-4xMyc construct or a CP-4xMyc construct in leaves of nrc2/3/4 N. benthamiana CRISPR mutant lines. (A-B) Single-plane confocal micrographs show the localization of both components of the inactive and active Rx-NRC2 system, together with PM marker RPW8.2-BFP. Scale bars represent 10 µm. (A) NRC2EEE-GFP and Rx-RFP co-localize in the cytoplasm prior to activation. (B) Upon co-expression of CP and activation of the system, NRC2EEE forms puncta associated with the PM while Rx remains in the cytoplasm.",
    "ncbi_link": "CRISPR: 
Myc: 
nrc2: 
CP: 7065758"
  },
  {
    "caption": "(C) Membrane enrichment assays are consistent with microscopy, showing that inactive NRC2EEE-GFP is mostly present in the soluble (cytoplasmic) fraction, whereas activated NRC2EEE-GFP exhibits equal distribution across soluble and membrane fractions. Rx is mostly present in the soluble fraction and exhibits no change upon activation of the system with CP. T = total, S = soluble, M = membrane. ATPase was used as a membrane marker. Rubisco was used as a marker for total and soluble fractions and visualized by Ponceau staining (PS). Red asterisks indicate bands matching the expected MW for each protein. The experiment was repeated two times.",
    "ncbi_link": "CP: 7065758"
  },
  {
    "caption": "(A-B) Single-plane confocal micrographs show the localization of NRC2 together with Rx or free RFP during PVX infection. C-terminally GFP-tagged NRC2EEE was co-infiltrated with either EV-RFP or Rx-RFP in leaves of nrc2/3/4 N. benthamiana CRISPR mutant lines and infected with PVX by agroinfection. Scale bars represent 10 µm. (A) In the absence of Rx, NRC2EEE-GFP is localized to the cytoplasm during PVX infection. (B) When Rx is present, NRC2EEE forms puncta associated with the PM during PVX infection.",
    "ncbi_link": "CRISPR: 
nrc2: "
  },
  {
    "caption": "A-C 10x106 ZsGreen- and luciferase-expressing U-2932, RC-K8 and RIVA cells were intravenously injected into six-week-old male (M) and female (F) MISTRG mice and monitored weekly using IVIS for at least four and up to six weeks. The color scales on the right indicate the radiance, i.e. the sum of the photons per second from each pixel inside the ROI/number of pixels (photons/sec/cm2/sr).",
    "ncbi_link": "luciferase: 
ZsGreen: "
  },
  {
    "caption": "10x106 ZsGreen- and luciferase-expressing U-2932, RC-K8 and RIVA cells were intravenously injected into six-week-old male (M) and female (F) MISTRG mice and monitored weekly using IVIS for at least four and up to six weeks. D The frequency of involvement of the indicated tissues is shown for one cohort of mice and is representative of two independently analyzed cohorts per cell line.",
    "ncbi_link": "luciferase: 
ZsGreen: "
  },
  {
    "caption": "E Gating strategy for the identification of U-2932 cells residing in spleen and bone marrow, among all leukocytes in these organs. Cells were stained for human and mouse CD45. Very few hCD45+ U-2932 cells were detectable in the spleen, whereas their frequencies were much higher in the bone marrow (BM). In BM, >90% of U-2932 cells were positive for ZsGreen. The green curve shows U-2932 cells recovered from BM, overlayed with unlabelled U-2932 cells grown in vitro (grey curve).",
    "ncbi_link": "ZsGreen: "
  },
  {
    "caption": "MISTRG mice were reconstituted or not at birth with human CD34+ cord blood HSPCs, and intravenously injected with RC-K8 cells at six weeks of age. The lymphoma burden at the study endpoint was quantified by ZsGreen expression and in the case of RC-K8 cells, also over time by IVIS (H).",
    "ncbi_link": "ZsGreen: "
  },
  {
    "caption": "The expression of the IL-6Rα (CD126) and signaling chains (gp130) was assessed by SYBR or Taqman qRT-PCR (B, C) respectively, on a panel of DLBCL cell lines. ABC- and GCB-DLBCL cell lines are color-coded in red and green; RC-K8 are depicted in grey, as their subtype is a matter of debate",
    "ncbi_link": "CD126: 3570
IL-6Rα: 3570
gp130: 3572"
  },
  {
    "caption": "E STAT3 phosphorylation as assessed by Western blotting of CD126-proficient (WT) or -deficient (ko) RC-K8 cells, with and without 1h of exposure to 50ng/ml hIL-6.",
    "ncbi_link": "CD126: 3570"
  },
  {
    "caption": "F Kinetics of STAT3 phosphorylation as assessed by Western blotting, of the IL-6-expressing SOCS1wt and SOCS1mut cell lines OCI-Ly3 and SU-DHL-2, under 1, 6 and 24h exposure to an IL-6-neutralizing antibody (α-IL-6, anti-IL-6 neutralizing antibody).",
    "ncbi_link": "SOCS1: 8651"
  },
  {
    "caption": "(F, G) Ribo-seq and RNA-seq  expression data of Cand2  in sham and TAC operated animals (CPM - count per million). One-way ANOVA, ** - P ≤ 0.01, n=2-4 biological replicates per group. Data information: Error bars indicate means ± SEM",
    "ncbi_link": "Cand2: 192226"
  },
  {
    "caption": "(J) Schematic representation of reporter consisting of human Cand2 5'UTR and downstream  Renilla luciferase coding sequence. A potential TOP-like motif is highlighted in a grey box. Black arrows indicate transcription start sites in the adult heart  according to the Database of Transcriptional Start Sites (Release 10.1). The effect of Cand2  5'UTR on translation measured by luciferase activity in normal conditions and after  mTORC1  block with Torin 1. eEF2 - positive control of reporter with defined 5'TOP motif and non-TOP 5'UTR of  β-actin used as a negative control. Total protein content in lysates used for  luciferase assay. t-test, n=4-5 biological replicates per group, ** - P ≤ 0.01, *** - P ≤ 0.001.",
    "ncbi_link": "luciferase: 
β-actin: 60
Cand2: 23066
mTORC1: 56717"
  },
  {
    "caption": "(C)  Immunofluorescent staining of paraffin  sections from hearts  from WT and Cand2 KO mice. CAND2 (stained in red), ACTIN (stained in green) and nuclei (stained with  DAPI, blue) in. Scale bar 20μm",
    "ncbi_link": "Cand2: 67088"
  },
  {
    "caption": "(E) NRCMs size measurement after Cand2 OE and 24h PE stimulation. Analyzed by One-way ANOVA. n>150 cells from n=3 independent experiments. Violin plot: the middle horizontal lane - median, upper lane - 3rd quartile, lower lane - 1st quartile. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Cand2: 192226"
  },
  {
    "caption": "(F) Nppa mRNA levels in vitro after  Cand2  OE and PE treatment measured by RT-qPCR. Analysed by One-way ANOVA. n=5-9 biological replicates per conditions. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Cand2: 192226
Nppa: 24602"
  },
  {
    "caption": "(J) Nppa and Nppb  mRNA levels 4 weeks after TAC in WT and Cand2  KO  mice measured by RT-qPCR. Analyzed by One-way ANOVA. n=6-13 mice per group. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001 ",
    "ncbi_link": "Cand2: 67088
Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "(B)  Immunoblots  and quantification of Grk5 protein levels in vitro after Cand2 KD with siRNA and after Cand2  OE with AAV6. t-test, n=4-5 biological replicates per group. Data information: Error bars indicate means ± SEM. * - P ≤ 0.05, *** - P ≤ 0.001.",
    "ncbi_link": "Cand2: 192226"
  },
  {
    "caption": "(F) Representative  immunoblot  of Grk5 protein levels and quantification in cytoplasmic  and  nuclear fractions from left ventricle lysates of WT and Cand2 KO mice after TAC surgery. Lamin B - nuclear  marker, Gapdh  - cytoplasmic marker. Analyzed by One-way ANOVA, n=3 biological replicates. Data information: Error bars indicate means ± SEM. * - P ≤ 0.05, *** - P ≤ 0.001. ",
    "ncbi_link": "Cand2: 67088"
  },
  {
    "caption": "(B) mRNA levels of MEF2-dependent genes Nr4a1  and Xirp2  in NRCMs with Cand2 KD for indicated groups. PE treatment for 24h (50uM). Analyzed by One-way ANOVA, n=6 biological replicates. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Cand2: 192226
Nr4a1: 79240
Xirp2: 311098"
  },
  {
    "caption": "(I) Grk5, Nppa, and MEF2  targets  Nr4a1  and Xirp2  mRNA levels in NRCMs  after  Raptor  KD. Analyzed by t-test, n=3 biological replicates per conditions. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Grk5: 59075
Nppa: 24602
Nr4a1: 79240
Raptor: 287871
Xirp2: 311098"
  },
  {
    "caption": "(B)  Cul1 neddylation  analyzed by  Western blot in NRCMs  depleted of  Cand2. NRCMs were treated with MLN4924 (100 nM) to block Cul1 neddylation. Quantification of neddylated  and unnedylated  Cul1  protein levels after MLN4924  treatment for 24h. t-test, n=4 biological replicates. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Cand2: 192226"
  },
  {
    "caption": "(D) Grk5  expression in NRCMs upon Cand2 KD and Cul1 neddylation inhibition (MLN) analysed by  immunoblot  and RT-qPCR. Analyzed by One-way ANOVA, n=4-5 biological replicates. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Cand2: 192226"
  },
  {
    "caption": "(H) mRNA levels of MEF2-dependent genes Nr4a1 and Xirp2 in  NRCMs for indicated groups. Analyzed by One-way ANOVA, n= 6 biological replicates. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001, **** - P ≤ 0.0001",
    "ncbi_link": "Nr4a1: 79240
Xirp2: 311098"
  },
  {
    "caption": "(C) Grk5 protein levels in vivo in LVs of WT and Cand2  KO mice 2 days after sham and TAC analyzed by  immunoblotting as well as quantification of mRNA levels analyzed by RT-qPCR. Analyzed by One-way ANOVA. n=3-5 biological replicates per group. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001.",
    "ncbi_link": "Cand2: 67088"
  },
  {
    "caption": "(D) Representative  immunoblot  and its quantification of protein levels of neddylated  and unnedylated  Cul1 in Cand2 KO  mice  compared to WT mice. Analyzed by t-test. n=5-8  mice per group. Cul1  neddylation was inhibited in C2C12 by MLN4924 (-/+ MLN) for neddylated Cul1 band detection. Data information: Error bars indicate means ± SEM; * - P ≤ 0.05, ** - P ≤ 0.01, *** - P ≤ 0.001.",
    "ncbi_link": "Cand2: 67088"
  },
  {
    "caption": "(a) Relative CK2α protein concentration over time following cytoplasmic microinjection of REF52 cells with the HA-tagged semisynthetic proteins bearing different modifications using immunocytochemistry with HA-specific antibody. Data represent mean values ± s.d. (b) Relative CK2α protein concentration following injection of β subunit together with CK2α proteins. Data represent mean values ± s.d. (c) Relative CK2α protein concentration following injection of proteasome inhibitor (1 μM MG132) together with unmodified CK2α protein. Data represent mean values ± s.d.",
    "ncbi_link": "CK2α: 1457"
  },
  {
    "caption": "(a) Pull-down experiments with semisynthetic HA-CK2α protein and recombinant Pin1. CK2α was immobilized using HA-specific (anti-HA) antibodies bound to protein G beads. Pin1 was incubated with immobilized CK2α for 20 min at 4 °C.",
    "ncbi_link": "CK2α: 1457
Pin1: 5300"
  },
  {
    "caption": "(b) Coimmunoprecipitation of endogenous Pin1 with CK2α. Pfa-containing and unmodified semisynthetic HA-CK2α proteins were spiked into REF52 cell lysates and immobilized using HA-specific antibodies. Input samples are shown for loading control.",
    "ncbi_link": "CK2α: 1457"
  },
  {
    "caption": "(c) Pull-down experiments with Pfa344 HA-CK2α protein and recombinant Pin1 in the presence of Pin1-specific or nonspecific IgY.",
    "ncbi_link": "Pin1: 5300"
  },
  {
    "caption": "(d) Relative CK2α protein concentration over time following microinjection of Pfa344 CK2α with Pin1-specific IgY or nonspecific IgY (control). Data represent mean values ± s.d. Full gels corresponding to those in panels a-c are in Supplementary Figures 10 and 11.",
    "ncbi_link": "CK2α: 1457
Pin1: 5300"
  },
  {
    "caption": "Phosphorimage analysis of in vitro CK2 kinase assays with protein substrates. All reactions were performed at 30 °C. Numbers indicate the concentration (nM) of product for each kinase reaction. (a) AHCYL2 substrate (25 ng μl−1) with 100 μM ATP and 10 nM CK2α ± 11 nM CK2β for 6 min. (b) NAP1L3 substrate (15 ng μl−1) with 100 μM ATP and 10 nM CK2α ± 11 nM CK2β for 6 min. (c) NIPBL substrate (50 ng μl−1) with 100 μM ATP and 5 nM CK2α ± 11 nM Pin1 for 5 min. Full gels corresponding to those in panels a-c are in Supplementary Figures 19 and 25.",
    "ncbi_link": "CK2α: 1457
CK2β: 1460
Pin1: 5300"
  },
  {
    "caption": "(s,t) Quantitative real-time PCR of orfs. 19.4325, 19.130, RIC1 on cDNA from Candida SC5314 (s) or the TOR1-1/TOR1 mutant (t) strains exposed to vehicle (open column), 10 ng ml−1 IL-17A (black column) or 15 nM rapamycin (grey column) for 4 h. The actual P-values are indicated (two-tailed t-test) (n=3).",
    "ncbi_link": "TOR1: 
TOR1-1: 
19.4325: 3637818
RIC1: 3639409
19.130: 3644040"
  },
  {
    "caption": "(w) orf. 19.5258 expression after 24-h Candida SC5314 exposure as in (n,o). Data are mean±s.d. (n=3). The actual P-values are indicated (two-tailed t-test).",
    "ncbi_link": "19.5258: 3642025"
  },
  {
    "caption": "(p-r) Cytospins of vaginal fluids from IL-17F-deficient (p), IL-17A-deficient (q) and C57BL/6 (r) mice intravaginally infected two days before with C.albicans SC5314 blastospores. Note the presence of hyphae in the vagina of IL-17F-deficient mice after May-Grünwald-Giemsa staining (scale bars, 20 μm). Shown is one representative experiment out of three.",
    "ncbi_link": "IL-17A: 16171
IL-17F: 257630"
  },
  {
    "caption": "(c) Failure of IL-17A to bind to wild-type (red square) or mutant C. albicans strains in which the three genes of the CRH family (UTR2, open light blue, CRH1, open black and CRH12, open blue square) had been deleted, and restoration of binding by CRH1 (black square) and CRH12 (blue square), but not UTR2 (light blue square), reconstitution. Data are mean±s.d. (n=3). P0.001 for red square, open light blue, black square and blue square (one-way analysis of variance Bonferroni post-test).",
    "ncbi_link": "CRH12: 
CRH1: 3638085
UTR2: 3636591"
  },
  {
    "caption": "(d,e) Cellular localization of bound IL-17A. Electron micrographs of ultrafine sections of C. albicans MKY 378 wild-type (d) or the crh11Δ mutant (e) incubated with biotinylated IL-17A and streptavidin gold-conjugated particles. Arrows indicate immunogold particles. Scale bars, 200 nm.",
    "ncbi_link": "crh11: "
  },
  {
    "caption": "Fungi were harvested from the stomachs of C57BL/6 (a-c), IL-17F-deficient (d-f) or IL-17A-deficient (g-i) mice infected with GFP-Candida for 2 days, and stained using PE-labeled antibody to IL-17A. Cells were green in (a,d and g), red upon staining with anti-IL17A-PE (b,e and h) and double stained in the merged images (c,f and i). Scale bars, 10 μm. Images are from one representative experiment out of two. (j-l) SEM images showing fungal germination in the stomachs of C57BL/6 mice (j), filamentation in IL-17F-deficient mice (k) and neither one in IL-17A-deficient (l) mice intragastrically infected 2 days before. Scale bars, 10 μm. (a-l) Images are from one representative experiment out of two.",
    "ncbi_link": "IL-17A: 16171
IL-17F: 257630"
  },
  {
    "caption": "(m-o) C57BL/6 mice were infected intragastrically with C. albicans MKY 378 strain (m) or the crh11Δ (n) and crh12Δ (o) mutants, and were monitored for fungal growth (log10 colony-forming units (CFU) at 2 (open circle) or 8 (black circle) days post infection). Data are mean±s.d. (n=3). The actual P-values are indicated (two-tailed t-test) for 2 and 8 days (m) and for 2 days (o). Fungal cells were untreated (none) or exposed to 10 ng ml−1 IL-17A for 4 h before injection.",
    "ncbi_link": "crh11: 
crh12: "
  },
  {
    "caption": "Candida SC5314 (a), TOR1-1/TOR1(b) and atg9Δ/atg9Δ (c) mutant strains were untreated (open column) or pre-incubated with IL-17A (filled column) for 4 h before exposure to neutrophils for additional 2 h before the assessment of adhesion, phagocytosis and killing. Error bars, mean±s.d. (n=3). The actual P-values are indicated (two-tailed t-test).",
    "ncbi_link": "TOR1-1: 
TOR1: 
atg9: 3635309"
  },
  {
    "caption": "(h-j) Log10 colony-forming units (CFU) at 2 days post infection with C. albicans SC5314 (wild-type) or different mutant strains in C57BL/6 (h), IL-17F-deficient (i) or IL-17A-deficient (j) mice. Data are mean±s.d. (n=3). The actual P-values are indicated (two-tailed t-test).",
    "ncbi_link": "IL-17A: 16171
IL-17F: 257630"
  },
  {
    "caption": "(m) ELISA assay showing failure of IL-17A to bind the Aspergillus mutant crf1Δ (blue square) as opposed to the wild-type strain AF293 (red square). Data are mean±s.d. (n =5). P-values ranged from 0.05 to 0.01, wild-type versus mutant strain exposed to 1 or 10 ng ml−1 IL-17A (one-way analysis of variance, Bonferroni post-test).",
    "ncbi_link": "crf1: "
  },
  {
    "caption": "(n-q) IL-17A promotes filamentation in the mutant crf1Δ (o) but not the wild-type AF293 (q) strain after 24-h exposure in liquid culture. Scale bars, 500 μm.",
    "ncbi_link": "crf1: "
  },
  {
    "caption": "(r,s) C57BL/6 mice were infected intranasally with the Aspergillus crf1Δ mutant (r) or the AF293 (s) strain and monitored for fungal growth (log10 colony-forming units (CFU)±s.d.) in the lungs 2 days later. Fungal cells were exposed or not (none) to 10 ng ml−1 IL-17A for 4 h, extensively washed and injected. Data are mean±s.d. (n=4). The actual P-values are indicated (two-tailed t-test).",
    "ncbi_link": "crf1: "
  },
  {
    "caption": "(D) HeLa cells were transfected with 10 nM control (n=84) or  Nup50 siRNA (n=171), 20 nM control (n=101) or Nup50 siRNA (n=157) and 40 nM control (n=86) or  Nup50 siRNA (n=204). 72 h post transfection, cells were fixed with 4% PFA  and stained  with antibodies against Nup50 and mAB414, chromatin was labeled with  DAPI. Scale bars: 50 µm. Quantitation of the mAB414 rim intensity at three different Nup50 RNAi and control oligo concentrations. The means are indicated as diamonds, error bars show the standard deviations. P-values have been calculated from a student t-test comparing the mean between the experimental conditions.",
    "ncbi_link": "Nup50: 10762"
  },
  {
    "caption": "(A) Mouse 3T3-NIH cells were transfected with 20 nM control, Nup50A, Nup50B or a combination of Nup50A and Nup50B  siRNA. After 72h cells were fixed and stained with mAB414 (green) and antibodies against mouse Nup50 (red). Chromatin is  stained with DAPI (blue). The merge of the three channels is shown on the left column. Scale bar: 50 µm. An insert shows a zoom on a representative  nucleus for each picture. Scale bar: 10 µm.",
    "ncbi_link": "Nup50A: 18141
Nup50B: 18141"
  },
  {
    "caption": "(A, B) Demembranated sperm chromatin was preincubated in  Xenopus egg  extract, depleted for  MEL28/ELYS or Nup50 (B) or control treated (Mock, A). After 10 min,  membranes were added to the reaction. Reactions were stopped at the indicated time points  by fixation and analyzed by confocal microscopy after  immunostaining with α-MEL28/ELYS  (A), α-Nup50 (B), and mAb414 (A, B). Chromatin  was stained  with  DAPI (blue in the overlay). Scale bar: 10 μm.",
    "ncbi_link": "ELYS: 397707
MEL28: 397707
Nup50: 503671///503675"
  },
  {
    "caption": "3 µM recombinant EGFP, EGFP-tagged MEL28/ELYS (aa 2290-2408) or  EGFP-tagged  Nup50 were incubated with empty or DNA-coated magnetic beads, which were chromatinized with Xenopus egg   extracts (right panel) or unchromatinized DNA-beads (left panel). After 3h the beads were re-isolated, washed, co-stained with DAPI  and analyzed by  confocal microscopy. Scale bar: 10 µm.",
    "ncbi_link": "EGFP: 
ELYS: 
MEL28: 397707
Nup50: 503671///503675"
  },
  {
    "caption": "(C)  HeLa cells were transfected with EGFP-Nup50 comprising different point mutations in the minimal NPC binding region and analyzed as in (A). Scale Bar: 10 µm.",
    "ncbi_link": "EGFP: 
Nup50: 18141"
  },
  {
    "caption": "(D)  GST-fusion constructs of the  Xenopus Nup50 minimal NPC binding fragment (aa 144-189) comprising no or single point mutations were incubated with Xenopus egg extracts. Starting material as well as bound proteins were analyzed by Western blotting with indicated antibodies. The quantitation shows the average MEL28/ELYS and Nup153 bead bound signal from three independent experiments, normalized to the signal of their respective wild-type GST fusion Data points from individual experiments are indicated.",
    "ncbi_link": "Nup50: 503671///503675"
  },
  {
    "caption": "(A) Confocal microscopy images of  nuclei  assembled for 120 min in mock depleted, Nup50 depleted (∆Nup50), and Nup50 depleted Xenopus egg extracts supplemented with recombinant wild-type Nup50  or different mutants. Nuclei  were fixed in 4% PFA and 0.5 % glutaraldehyde, stained  for NPCs  (mAB414) and the chromatin  (DAPI). Scale bar: 10 µm. (B) Average percentage of mAB414 positive  nuclei for 100 randomly chosen chromatin substrates in each of at least three independent experiments shown in (A). Data points from the individual experiments are indicated. ",
    "ncbi_link": "Nup50: 503671///503675"
  },
  {
    "caption": "(C) Confocal microscopy  images of  nuclei  assembled with N-terminal Nup50 truncations and an minimal N-terminal fragment. Samples were analyzed as in (A). (D) Average percentage of mAB414 positive nuclei  for 100 randomly chosen  chromatin substrates in each of at least three independent experiments shown in (C). Data points from the individual experiments are indicated. ",
    "ncbi_link": "Nup50: 503671///503675"
  },
  {
    "caption": "(B)  Confocal microscopy images of fixed  nuclei  assembled for 120 min in mock depleted (mock) and Nup50 depleted (∆Nup50)  Xenopus egg  extracts supplemented with recombinant  mouse Nup50  orthologues. Nuclei  were stained for Nup50 (Nup50  antibody for Xenopus protein,  His6  for  mouse protein) and NPCs (mAB414, red) on the chromatin  (DAPI). Scale bar: 10 µm. (C) The average percentage of mAB414 positive nuclei for 100 randomly chosen  chromatin substrates in each of three independent experiments (performed as in B) is shown. Data points from individual experiments are indicated. ",
    "ncbi_link": "Nup50: 503671///503675"
  },
  {
    "caption": "HEK293T cells were transfected with empty  FLAG-tag vector as a control or FLAG-Nup50 N-terminal fragment (aa 1-120 of the human sequence). 24 h post transfection cells were lysed,  FLAG-tagged proteins immuno-isolated and analyzed by mass spectrometry with the Volcano blot showing the identified interactors of Nup50 (yellow, data from three independent experiments) Data points from individual experiments are indicated. KPNA2  is the gene name of  importin α.",
    "ncbi_link": "FLAG: 
Nup50: 10762"
  },
  {
    "caption": "HEK293T  cells were transfected with empty FLAG-tag vector as a control or FLAG-Nup50 N-terminal fragment (aa 1-120 of the human sequence). 24 h post transfection cells were lysed,  FLAG-tagged proteins immuno-isolated and analyzed by  western blotting (B), with 10% of the inputs loaded. The quantification of the  western blot (B, lower panel) shows the mean signal intensity normalized on the input of at least two independent experiments. Data points from individual experiments are indicated.",
    "ncbi_link": "FLAG: 
Nup50: 10762"
  },
  {
    "caption": "(G) Confocal microscopy images of nuclei  assembled for 120 min in mock depleted, Nup50 depleted (∆Nup50), and  Nup50 depleted Xenopus egg extracts supplemented with recombinant  Xenopus  wild-type  Nup50 or RCC1 binding mutants. Nuclei  were fixed in 4 % PFA and 0.5 % glutaraldehyde, stained for NPCs  (mAB414) and the chromatin (DAPI). Scale bar: 10 µm. Quantitation shows the average percentage of  mAB414 positive  nuclei for 100 randomly chosen chromatin substrates in each of three independent experiments. Individual data points are indicated (H) Confocal microscopy images of nuclei  assembled for 120 min in mock depleted, Nup50  depleted (∆Nup50), and Nup50 depleted Xenopus egg extracts supplemented with  RCC1  excess as indicated. Nuclei  were fixed in 4 %  PFA and 0.5 % glutaraldehyde,  stained for NPCs (mAB414) and the  chromatin (DAPI). Scale bar: 10 µm. Quantitation shows the average percentage of  mAB414 positive nuclei for 100 randomly chosen  chromatin substrates in each of three independent experiments. Individual data points are indicated. ",
    "ncbi_link": "Nup50: 503671///503675"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. (A) The scatter plot shows the apparent Young's moduli obtained by AFM analysis. Bars represent the median values of the distributions. The immunoblot shows UBTD1 siRNA knock-down efficiency.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. (B) Immunoblots (left) and quantification (right) show levels of GST-ROCK associated GTP-bound RhoA (RhoA-GTP) and total RhoA in lysates (RhoA) in confluent cells. Immunoblot of UBTD1 shows the level of siRNA depletion.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. (C) Representative confocal images of focal adhesion (paxillin) and actin cytoskeleton (phalloidin) and outlines of focal adhesions using threshold-based image. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. (D) Cell area, number and area of focal adhesion were quantified (ImageJ) using the analysis as shown (C).",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. Sub-confluent DU145 (E) cells were seeded on two matrices of different stiffnesses (4 and 12 kPa). Representative heat map (left) and quantification (right) showing contractile forces generate by cells plated on 4kPa or 12kPa hydrogel.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "A549 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. Sub-confluent A549 (F) cells were seeded on two matrices of different stiffnesses (4 and 12 kPa). Representative heat map (left) and quantification (right) showing contractile forces generate by cells plated on 4kPa or 12kPa hydrogel.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. (G) Confluent DU145 cells were seeded on 12 kPa matrix. Representative heat map (left) and quantification (right) showing contractile forces generate by cells plated on 12kPa hydrogel.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool or siUBTD1single1 or single2) for 24 h and plated on fibronectin-coated glass coverslips. (H) Representative confocal images of YAP and UBTD1 localization on two matrices of different stiffness. DU145 cells were grown on collagen/acrylamide-coated glass coverslips (soft) or directly on glass coverslips (stiff). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "Proximal ligation assay monitoring (left) and quantification (right) of UBTD1 association with E-cadherin or β-catenin in DU145 cells transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "Immunoblots of UBTD1, β-catenin and YAP after subcellular fractionation of confluent DU145 cells transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool). EGFR, RhoGDI and Lamin A/C were used as controls for the membrane (M), cytosol (C) and nucleus (N) compartments, respectively.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). (B) Immunoblots of p-YAP (ser127), YAP and UBTD1 (left) and quantification of YAP and p-YAP/YAP levels (right) in control or UBTD1-depleted DU145 at low and high cell density. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin was used as a loading controls. , immunoblots for the loading control (actin) and UBTD1 knock-down efficiency (UBTD1) are duplicated because they belong to the same experiment shown in both panels.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). (C) Immunoblots of the Hippo signaling pathway using phosphorylated (p-ser909LATS and p-thr183MST1/p-thr180MST2) and total LATS, MST at low and high DU145 cells density. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin and Rho-GDI were used as loading controls. , immunoblots for the loading control (actin) and UBTD1 knock-down efficiency (UBTD1) are duplicated because they belong to the same experiment shown in both panels.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). Immunoblots (up) and quantification (down) of YAP levels in confluent (D) DU145 UBTD1 depleted cells treated or not with cycloheximide (CHX) for 2h. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin was used as a loading control.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "A549 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). Immunoblots (up) and quantification (down) of YAP levels in confluent (E) A549 UBTD1 depleted cells treated or not with cycloheximide (CHX) for 2h. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin was used as a loading control.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells or A549 cells were transfected for 48h with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). Immunoblots (up) and quantification (down) showing YAP levels in UBTD1 depleted confluent DU145 A549 cells treated or not with MG132 for 6h. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Actin was used as a loading control.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(C) Proximal ligation assay monitoring (left) and quantification (right) of UBTD1 associated with YAP of DU145 and A549 cells transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(E) Co-immunoprecipitation in confluent DU145 cells between endogenous β-TrCP, Ubch5c, YAP and β-catenin. DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool or siUBTD1single). β-TrCP was used as bait. IgG isotype was used as a negative control. Immunoblot of UBTD1 shows the level of siRNA-mediated depletion.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "Proximal ligation assay monitoring (F) of β-TrCP associated with Ubch5, YAP or β-catenin in DU145 cells transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "quantification (G) of β-TrCP associated with Ubch5, YAP or β-catenin in DU145 cells transfected with the indicated siRNA (control, siCTRL; UBTD1: siUBTD1pool).",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(H) Immunoblots show YAP ubiquitylation in HEK cells in different experimental conditions. Cells were transfected, as indicated, with expression vectors of histidine-tagged ubiquitin (His-Ub) together with control siRNA or UBTD1 siRNA. His-Ub crosslinked forms of YAP were purified (IP: His) and the immunoblot of YAP showed YAP ubiquitylation. The immunoblot of YAP (lower panel) was performed in parallel to verify the amounts of YAP protein engaged in the His-Ub purifications. The immunoblot of UBTD1 shows the level of siRNA depletion.",
    "ncbi_link": "UBTD1: 80019
YAP: 10413"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). (A) Representative wide-field immunofluorescence images (left) and quantification (right) showing endogenous YAP nuclear translocation in DU145 cells after UBTD1 depletion. Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool). (B) Quantification of CTGF1, CYR61 and BIRC5 mRNA levels.",
    "ncbi_link": "BIRC5: 332
CYR61: 3491
CTGF1: 1490
UBTD1: 80019"
  },
  {
    "caption": "(C) Immunoblots of YAP in DU145 cells depleted (siUBTD1single2) or not (siCTRL) for UBTD1 and transfected or not with GFP-UBTD1 (+). Immunoblot of UBTD1 shows the level of siRNA-mediated depletion. Immunoblot of GFP shows the level of UBTD1 transfection. CHC was used as a loading control.",
    "ncbi_link": "GFP: 
UBTD1: 80019"
  },
  {
    "caption": "(D) Representative confocal immunofluorescence images (left) and quantification (right) showing endogenous YAP nuclear translocation in DU145 cells depleted (siUBTD1single2) or not (siCTRL) for UBTD1 and transfected or not with GFP-UBTD1. Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "GFP: 
UBTD1: 80019"
  },
  {
    "caption": "(E) Immunoblots of p-YAP and YAP in DU145 control cells (siCTRL) or depleted for LATS1 and LATS2 (siLATS1+siLATS2) and/or UBTD1 (siUBTD1pool). Immunoblot of p-YAP reflects the activity of the Hippo pathway. Immunoblot of UBTD1 and LATS show siRNA knock-down efficiency. Actin was used as a loading control.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
UBTD1: 80019"
  },
  {
    "caption": "Representative confocal immunofluorescence images (F) showing endogenous YAP nuclear translocation in DU145 control cells (siCTRL) or depleted for LATS1 and LATS2 (siLATS1+siLATS2) and/or UBTD1 (siUBTD1pool). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
UBTD1: 80019"
  },
  {
    "caption": "quantification (G) showing endogenous YAP nuclear translocation in DU145 control cells (siCTRL) or depleted for LATS1 and LATS2 (siLATS1+siLATS2) and/or UBTD1 (siUBTD1pool).",
    "ncbi_link": "LATS1: 9113
LATS2: 26524
UBTD1: 80019"
  },
  {
    "caption": "(H) Immunoblots of YAP in DU145 control (siCTRL) or depleted for ROCK1 (siROCK1) or ROCK2 (siROCK2) and/or UBTD1 (siUBTD1pool). Immunoblots of UBTD1, ROCK1 and ROCK2 show the level of siRNA knock-down efficiency. Actin was used as a loading control.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475
UBTD1: 80019"
  },
  {
    "caption": "Representative confocal immunofluorescence images (I) showing endogenous YAP localization in DU145 control cells (siCTRL) or depleted for ROCK1 (siROCK1) or ROCK2 (siROCK2) and/or UBTD1 (siUBTD1pool). Nuclei were stained with DAPI (Blue) on the MERGE image.",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475
UBTD1: 80019"
  },
  {
    "caption": "quantification (J) showing endogenous YAP localization in DU145 control cells (siCTRL) or depleted for ROCK1 (siROCK1) or ROCK2 (siROCK2) and/or UBTD1 (siUBTD1pool).",
    "ncbi_link": "ROCK1: 6093
ROCK2: 9475
UBTD1: 80019"
  },
  {
    "caption": "(K) Quantification of CTGF1, CYR61, UBTD1 and BIRC5 mRNA in DU145 control cells (siCTRL) or depleted for ROCK1 (siROCK1) or ROCK2 (siROCK2) and/or UBTD1 (siUBTD1pool).",
    "ncbi_link": "BIRC5: 332
CYR61: 3491
CTGF1: 1490
ROCK1: 6093
ROCK2: 9475
UBTD1: 80019"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool or siUBTD1single1; UBTD1 +YAP+TAZ, siUBTD1single1+siYAPsingle1+ siTAZsingle1 or siUBTD1single1+siYAPsingle2+ siTAZsingle2). (A) Quantification of EMT marker genes (vimentin, slug, snail, fibronectin, α-SMA, E-cadherin) and UBTD1.",
    "ncbi_link": "snail: 
α-SMA: 59
E-cadherin: 999
fibronectin: 2335
slug: 6591
UBTD1: 80019
vimentin: 7431
TAZ: 25937
YAP: 10413"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool or siUBTD1single1; UBTD1 +YAP+TAZ, siUBTD1single1+siYAPsingle1+ siTAZsingle1 or siUBTD1single1+siYAPsingle2+ siTAZsingle2). (C) Quantification of DU145 cell migration in Transwell chamber inserts.",
    "ncbi_link": "UBTD1: 80019
TAZ: 25937
YAP: 10413"
  },
  {
    "caption": "DU145 cells were transfected with the indicated siRNA (control, siCTRL; UBTD1, siUBTD1pool or siUBTD1single1; UBTD1 +YAP+TAZ, siUBTD1single1+siYAPsingle1+ siTAZsingle1 or siUBTD1single1+siYAPsingle2+ siTAZsingle2). (D) Quantification of DU145 cell invasion in Transwell chamber inserts.",
    "ncbi_link": "UBTD1: 80019
TAZ: 25937
YAP: 10413"
  },
  {
    "caption": "(E) Invasive properties of human prostate tumoroids depleted for UBTD1.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(F) Quantification of UBTD1 mRNA levels in prostate tumor (n=70) and adjacent normal tissues (n=47).",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(I) The levels of UBTD1 mRNA in grade 3 prostate adenocarcinoma patients (56 patients) are correlated with overall survival (OS). OS was calculated from patient subgroups with mRNA levels that were less or greater than the first quartile value.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "(J) The levels of UBTD1 mRNA in lung adenocarcinoma patients (522 patients) are correlated with OS.",
    "ncbi_link": "UBTD1: 80019"
  },
  {
    "caption": "Lipid hydrolyzing activity assayed in the presence of different phospholipids using purified PLDα6 from E. coli. Solid bars are activities assayed using purified PLDα6 whereas open bars were empty vector control that used an equal volume of eluents from bacteria containing the empty vector that was identically processed as those expressing PLDα6. Values are means ± SD (n = 3 biological replicates).",
    "ncbi_link": "PLDα6: "
  },
  {
    "caption": "Total lipid levels in WT, pldα6 and COM without and with 10 μM GA3. Leaf samples (15 seedling each) from 4-leaf stage rice (Dongjin background) were collected and lipids were extracted and profiled using ESI-tandem mass spectrometry. Values are means ± SD (n = 3 biological replicates)). MGDG, monogalactosyldiacylglycerol; DGDG, digalactosyldiacylglycerol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PS, phosphatidylserine; PA, phosphatidic acid.",
    "ncbi_link": "pldα6: "
  },
  {
    "caption": "Phospholipid species in WT, pldα6 and COM. Leaf samples (15 seedling each) from 4-leaf stage rice (Dongjin background) were collected and the different phospholipid species including carbon number and double bond number were determined. Values are means ± SD (n = 3 biological replicates). GA3 was dissolved in ethanol and seedlings treated with the same ethanol concentration were used as control.",
    "ncbi_link": "pldα6: "
  },
  {
    "caption": "PLDα6-GFP distribution in rice protoplasts with different concentrations of GA3 or IAA. Protoplasts from 12-day old rice (ZH11 background) leaf sheath tissue were collected. Rice protoplasts were transfected with pM999-PLDα6 for 12 hours. After that, GA3 or IAA was added to protoplasts and 2 hours later, confocal images of protoplasts are shown. pM999-GFP refers to the empty vector with GFP only that was transformed as control and Ghd7-RFP was a nucleus marker. Scale bar = 10 μm.",
    "ncbi_link": "PLDα6: "
  },
  {
    "caption": "Subcellular location of GID1 in WT and pldα6 protoplasts with or without GA3 treatments. Cells for 12 hours after transformation were treated with or without 10 μM GA3 for two hours. Bars = 10 μm.",
    "ncbi_link": "pldα6: "
  },
  {
    "caption": "Immunoblotting of subcellular fractions of GID1 expressed in WT and pldα6 protoplasts. After 2-hour treatment with 10 μM GA3, total (T), soluble (S) and nuclear (N) protein fractions were isolated from 10 samples of protoplasts. Equal amount of each sample was loaded for SDS-PAGE and immunoblotting.",
    "ncbi_link": "pldα6: "
  },
  {
    "caption": "Protoplasts of WT and pldα6 from 12-day old stage leaf sheath were collected and transfected with a pM999-SLR1 construct, incubated for 12 hours and then treated with 10 μM GA3 for 0, 3, and 9 hours. The first column, fluorescence from GFP; the second, red fluorescence from the nucleus marker Ghd7; the third, bright field, and the fourth, overlay of the three channels. All confocal images were scanned using similar laser gain and offset settings. Bars = 10 μm.",
    "ncbi_link": "pldα6: "
  },
  {
    "caption": " (f) GFP in vivo fluorescence post intradermal injection of chitin oligomers into LysMEGFP/+ C57BL/6 mice (n=3/group) Data information represent data (mean+SEM) combined from 'n' (given in brackets for each panel) technical or biological replicate mic",
    "ncbi_link": "LysM: 17105"
  },
  {
    "caption": "TNF released from WT or Myd88 (A KO BMDM (total n=6-9/group combined from 3 experiments) Data information: I represent data (mean+SEM) combined from 'n' technical or biological replicate mic Student' t-test",
    "ncbi_link": "Myd88: 17874"
  },
  {
    "caption": "TNF released from W or Tlr KO BMDM (total n=6-9/group combined from 3 experiments) Student's t-tes",
    "ncbi_link": "Tlr: 24088"
  },
  {
    "caption": " (C) IL-6 released from primary MoMacs (n=5) treated with non-targeting (NT), TLR2- or MyD88-specific siRNA relative to NT condition one-sample t-tes",
    "ncbi_link": "MyD88: 4615
TLR2: 7097"
  },
  {
    "caption": " (E) IL-6 protein released from mock or TLR2 Cas9-CRISPR-edited THP-1 cells (n=3) I one representative of 'n' independent experiments is shown (mean+SD) ), Student's t-tes",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": " (F) NF-κB activity in empty vector (EV) or TLR2-transfected HEK293T cells (n=3) I one representative of 'n' independent experiments is shown (mean+SD) ",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": " (G) MPO release from intradermally injected WT or Tlr2 KO mice (n=5-15 biopsies each) Data information I represent data (mean+SEM) combined from 'n' technical or biological replicate mic ), Student's t-tes",
    "ncbi_link": "Tlr2: 24088"
  },
  {
    "caption": " (H) BALF IL-6 and TNF from intratracheally treated WT or Tlr2 KO mice (n=4-5 mice each) one-way ANOVA with Dunnett's multiple compariso ",
    "ncbi_link": "Tlr2: 24088"
  },
  {
    "caption": " (I) Relative IL10 mRNA in whole blood of WT or heterozygous TLR2 R753Q carriers (n=5 each) Data information: I represent data (mean+SEM) combined from 'n' technical or biological replicate (human donor * p<0.05 according to Mann-Whitney",
    "ncbi_link": "IL10: 3586
TLR2: 7097"
  },
  {
    "caption": " (A) NF-κB activity in TLR2-transfected HEK293T cells (n=3) Data information I one representative of 'n' independent experiments is shown (mean+SD) Student's t-tes",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": " (G) Relative cytokine mRNAs in whole blood stimulation (n=5-13) Data information represent data (mean+SEM) from 'n' technical or biological replicates (donors) * p<0.05 according to Wilcoxon signed rank su",
    "ncbi_link": "cytokine: 3586"
  },
  {
    "caption": "(H) NF-κB activation in TLR2-transfected HEK293T cells (n=3 Data information I one representative of 'n' independent experiments is shown (for asmean+SD) ), Student's t-tes",
    "ncbi_link": "TLR2: 7097"
  },
  {
    "caption": "(B) ZNF366 expression across clusters.",
    "ncbi_link": "ZNF366: 167465"
  },
  {
    "caption": "MAFF expression was silenced using a lentivirus containing shRNA. (H) Protein quantification by Western Blot after 5 days. Actin was used as loading control. Representative results are shown (n=4 biological replicates). Quantification was performed by densitometry. Each symbol represents an individual donor. Paired one-way Anova.",
    "ncbi_link": "MAFF: 23764"
  },
  {
    "caption": "MAFF expression was silenced using a lentivirus containing shRNA. (I) Mo-mac and mo-DC differentiation after 5 days was assessed by flow cytometry. One representative donor is shown (n=7 biological replicates). DN = double negative. Proportion of mo-DC, mo-Mac and DN cells after 5 days. Median is shown (n=7 biological replicates). Paired one-way Anova.",
    "ncbi_link": "MAFF: 23764"
  },
  {
    "caption": "YTHDC1 accumulation within nSBs was arrested by METTL3 knockdown. HeLa cells were stained as described in Figure 1C. Scale bar: 10 µm. Box plot of relative intensities of YTHDC1 to HSATIII within nSBs in individual nuclei (n=30). The mean is indicated with X. The first and third quartiles are the ends of the box, the median is indicated with a vertical line in the box, and the minimum and maximum except for the outliers are the ends of the whiskers. The outliers are indicated with open circles. P-values (Kruskal-Wallis test, followed by Dunn's multiple comparison test) are shown above.",
    "ncbi_link": "METTL3: 56339"
  },
  {
    "caption": "Scatter plot of LogFC of whole introns (grey) and HSATIII-target introns (blue) upon SRSF9 KD (X-axis) and HSATIII KD (Y-axis). 51,469 and 548 introns are plotted as whole introns and previously-reported HSATIII-target introns, respectively. Pearson's correlation (r) is indicated above.",
    "ncbi_link": "SRSF9: 8683"
  },
  {
    "caption": "Read maps represent RNA-seq data of nuclear poly (A)+ RNAs (upper panel, biological triplicate) and m6A-RIP RNAs (lower panel, biological duplicate) in control and HSATIII KD cells. The exon numbers of the FAM214A gene are indicated below. The retaining intron and the m6A peak are marked by a red line and arrow, respectively. For the entire FAM214A region, see also Figure EV4B.",
    "ncbi_link": "FAM214A: 56204"
  },
  {
    "caption": "(A) Wild type (left and middle panels) and p53-/- (right panel) HCT116 cells were transfected with control (mixture of control DS scrambledNeg, siLuci, and siGFP) or GRWD1-targeting (mixture of siGRWD1-3 and 4) siRNAs for 36 h, treated with 5 nM actinomycin D, and harvested at the indicated times. Whole cell extracts were analyzed by immunoblotting with the indicated antibodies. Coomassie Brilliant Blue (CBB) staining serves as a loading control.",
    "ncbi_link": "GRWD1: 83743
p53: 7157"
  },
  {
    "caption": "(B) Control U2OS cells infected with control retroviruses with the empty vector and U2OS cells overexpressing the siRNA-resistant HA-GRWD1 were treated and analyzed as above.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(C) HCT116 cells were transfected with control (mixture of control DS scrambledNeg, siLuci, and siGFP) or GRWD1-targeting (mixture of siGRWD1-3 and 4) siRNAs for 24 h, treated with 50 µg/ml cycloheximide, and harvested at the indicated times. Whole cell extracts were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(D) HFF2/T cells stably overexpressing HA-GRWD1 were established by retroviral infection. Cells were cultured in the presence or absence of actinomycin D (5 nM) for 12h and then treated with or without MG132 (20uM) for 6 h as indicated. Whole cell extracts were analyzed as above.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(E) Control and HA-GRWD1-overexpressing HFF2/T cells were first treated with actinomycin D (5nM) for 12 h, then further treated with 50 ug/ml cycloheximide, and harvested at the indicated times. Whole cell extracts were analyzed by immunoblotting with the indicated antibodies. The means and SDs from two independent experiments are shown.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(A) U2OS cells were transfected with control (mixture of control DS scrambledNeg, siLuci, and siGFP) or GRWD1-targeting (mixture of siGRWD1-3 and 4 or siGRWD1-1) siRNAs for 24 h. Whole cell extracts were then analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(D) HCT116 cells were transfected with control (mixture of control siLuci and siGFP) or GRWD1-targeting (mixture of siGRWD1-3 and 4 or siGRWD1-1) siRNAs for 24 h and then immunostained as above. Scale bar, 20 um.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(A) 293T cells were co-transfected with HA-GRWD1 (1.6 ug) and RPL5-FLAG (2.4 ug) or RPL11-FLAG (2.4 ug) as indicated for 42h and subjected to immunoprecipitation with anti-FLAG antibody. Immunoprecipitates (IPs) and 3.125% of inputs were immunoblotted with the indicated antibodies. *, immunoglobulin light chains.",
    "ncbi_link": "RPL11: 6135
RPL5: 6125"
  },
  {
    "caption": "(E) Cell lysates were prepared from 293T cells transfected with wild-type (WT) HA-GRWD1-FLAG (12 µg) or various N-terminal truncated mutants of HA-GRWD1-FLAG (12 µg) for 42h, and then subjected to GST pull-down assay with purified GST-RPL11 or GST. Bound proteins were analyzed by CBB staining (GST and GSR-RPL11) and immunoblotting with the indicated antibodies. *, non-specific bands.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(G) HCT116 cells were transfected with RPL11-FLAG expression vector (0.56 ug) or empty vector (0.56 ug) for 24 h and then treated with 5 nM actinomycinD or vehicle (PBS) for 12 h. The cells were first extracted with Triton X-100 to remove nucleoplasmic proteins, double-immunostained with anti-GRWD1 antibody (green) and anti-FLAG M2 antibody (red), and counterstained with DAPI. Scale bar, 20 um.",
    "ncbi_link": "RPL11: 6135"
  },
  {
    "caption": "(A) H1299 cells were co-transfected with the indicated expression vectors (p53, 7.5 ng; HA-Ub, 0.5 ug; His-Xpress-MDM2, 2 ug; RPL11-FLAG, 1 ug; HA-GRWD1-FLAG, 1.5 ug; GFP, 0.04 ug) for 48 h and analyzed by immunoblotting with the indicated antibodies. GFP serves as a control protein to show equal transfection efficiencies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135
p53: 7157
Ub: 7314///7311///6233///7316"
  },
  {
    "caption": "(B) Lysates were prepared from 293T cells co-transfected with His-Xpress-MDM2 (1.2 ug), FLAG-RPL11 (1.8 ug), and HA-GRWD1 (1 ug) as indicated for 42 h and then immunoprecipitated with anti-FLAG antibody. Immunoprecipitates (IPs) and 1.5% of inputs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135"
  },
  {
    "caption": "(C) In vivo ubiquitination assay to detect MDM2 autoubiquitination in H1299 cells. Lysates were prepared from H1299 cells transfected with the indicated expression vectors (His-Xpress-MDM2, 2 ug; HA-Ub, 0.5 ug; RPL11-FLAG, 1 ug; HA-GRWD1-FLAG, 1.5 ug) for 48 h, treated with proteasome inhibitors for 6 h before harvest, and then immunoprecipitated with anti-MDM2 antibody. Immunoprecipitates (IPs) and inputs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135
Ub: 7314///7311///6233///7316"
  },
  {
    "caption": "(D) In vitro ubiquitination of p53 by immunopurified MDM2. His-Xpress-MDM2 was immunopurified from transfected 293T cells with anti-Omni probe antibody. Recombinant p53 was incubated with E1, E2 (UbcH5a), His-ubiquitin, ATP, GST-RPL11, GRWD1-His, and immunopurified His-Xpress-MDM2 or control immunoprecipitates at 30℃ for 120 min as indicated. The samples were resolved by SDS-PAGE followed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135"
  },
  {
    "caption": "(A) Expression of the introduced proteins and the effect on p53. HFF2/T cells stably expressing HA-GRWD1, E7, and KRAS G12V were established with retroviral vectors and analyzed by immunoblotting with the indicated antibodies. *, endogenous RAS proteins.",
    "ncbi_link": "E7: 1489079
GRWD1: 83743
KRAS: 3845"
  },
  {
    "caption": "(B and C) Anchorage-independent growth of HFF2/T cells overexpressing E7 with or without HA-GRWD1. Three weeks after seeding, images were acquired and colonies >100 µm in diameter were counted. Representative images are shown in (B). Scale bars, 500 um. Average numbers of colonies per field, with SDs, are shown in (C). Six randomly selected areas were counted per sample.",
    "ncbi_link": "E7: 1489079
GRWD1: 83743"
  },
  {
    "caption": "(D and E) Anchorage-independent growth of HFF2/T cells overexpressing E7 and activated KRAS G12V with or without HA-GRWD1. At 9 days after seeding, the colonies were analyzed as above. Representative images are shown in (D). Scale bars, 500 um. The average numbers of colonies (>200 um in diameter) per field, with SDs, are shown in (E). Twenty randomly selected areas were counted.",
    "ncbi_link": "E7: 1489079
GRWD1: 83743
KRAS: 3845"
  },
  {
    "caption": "(F) Tumorigenesis of HFF2/T cells expressing E7 and KRAS G12V with or without HA-GRWD1. Cells were subcutaneously injected into nude mice (1 x 106 cells/mouse), and tumor size was measured. Average tumor volumes, with SDs, are shown (n=5).",
    "ncbi_link": "E7: 1489079
GRWD1: 83743
KRAS: 3845"
  },
  {
    "caption": "(G) High expression of GRWD1 is associated with poor prognosis of brain lower grade glioma patients with wild type p53 but not with mutated p53. The data were obtained from the TCGA databases (the cBioPortal for Cancer Genomics; http://www.cbioportal.org). For detail, see Materials and Methods.",
    "ncbi_link": "GRWD1: 83743
p53: 7157"
  },
  {
    "caption": "(A) 293T cells were co-transfected with HA-GRWD1 wild-type (WT) (0.5 ug) or HA-GRWD1 Δ1-136 (3.5 ug) and RPL11-FLAG (1.5 ug) as indicated for 42h, and then immunoprecipitated with an anti-FLAG antibody. Immunoprecipitates (IPs) and 1.6% of inputs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743
RPL11: 6135"
  },
  {
    "caption": "(B) 293T cells were co-transfected with His-Xpress-MDM2 (0.6 ug), RPL11-FLAG (0.9 ug), and HA-GRWD1 WT (0.5 ug) or HA-GRWD1 Δ1-136 (4.5 ug) as indicated for 42h and subjected to immunoprecipitation with an anti-FLAG antibody. Immunoprecipitates (IPs) and 1.6% of inputs were immunoblotted with the indicated antibodies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135"
  },
  {
    "caption": "(C) H1299 cells were co-transfected with the indicated expression vectors (p53, 7.5 ng; HA-Ub, 0.5 ug; His-Xpress-MDM2, 2 ug; RPL11-FLAG, 1 ug; HA-GRWD1-FLAG WT, 1.5 ug; HA-GRWD1-FLAG Δ1-136, 1.5 ug; GFP, 0.04 ug) for 48 h, and then analyzed by immunoblotting with the indicated antibodies. GFP serves as a control protein to show equal transfection efficiencies.",
    "ncbi_link": "GRWD1: 83743
MDM2: 4193
RPL11: 6135
p53: 7157
Ub: 7311///6233///7316///7314"
  },
  {
    "caption": "(D) HFF2/T cells stably expressing HA-GRWD1 wild-type (WT) or Δ1-136, E7, and KRAS G12V were established using retroviral vectors and analyzed by immunoblotting with the indicated antibodies. *, endogenous RAS proteins.",
    "ncbi_link": "GRWD1: 83743"
  },
  {
    "caption": "(E and F) Anchorage-independent growth of HFF2/T cells overexpressing E7 and activated KRAS G12V with HA-GRWD1 WT or Δ1-136 (or without HA-GRWD1). At 9 days after seeding, colonies were analyzed as above. Representative images are shown in (E). Scale bars, 500 um. Average numbers of colonies (>200 um in diameter) per photographed area with SDs are shown in (F). Seventy randomly selected areas were counted.",
    "ncbi_link": "E7: 1489079
GRWD1: 83743
KRAS: 3845"
  },
  {
    "caption": "C,D,E Examples of embryos expressing the tFT-Bcd reporter with C: mCherry-sfGFP-Bcd, D: fmCherry-sfGFP-Bcd, and E: mCherry-sfGFP. For all, (i) Images of \"shells\" of embryos in early n.c. 14. 3D images of the embryos were generated, and then the interior of the embryo was erased, leaving only the embryo cortex to improve clarity (ii) Mean AP intensity profile of each color for the embryo in i. Shade region represents ±1 s.d. Inset shows same profiles after multiplication of red intensity by constant factor. Data binned into 10 µm bins (n=4 embryos). (iii) Ratio of green over red signal, reflecting protein age. The thin lines represent individual embryos, while the thick solid line is the mean. The solid dashed line depicts the mean green/red ratio for a line with the tFT-Bcd reporter but lacking endogenous Bcd (BcdE1 mutant, n=4).",
    "ncbi_link": "Bcd: 40830"
  },
  {
    "caption": "D The age of Bcd and its gradient are unaltered in fsd mutant. Comparison of a representative y/w embryo (left) and loss-of-function mutation fsdKG02393 (right) are shown. Both embryos have the tFT-Bcd construct in the same locus, are in early n.c. 14, were imaged side-by-side under identical conditions, and are displayed with the same settings. Embryo \"shells\" are displayed.",
    "ncbi_link": "fsd: 36463"
  },
  {
    "caption": "E Quantification of embryos Fluorescence intensity from sfGFP (green) and mCherry (magenta) for wt (N=8, filled circles) and fsd (N=6, open squares) at early cycle 14. Inset: tFT-Bcd ratio for wt (black) and FSD (gray) embryos.",
    "ncbi_link": "fsd: 36463
FSD: 36463"
  },
  {
    "caption": "G, Fluorescent in situ hybridization for cd74a, tnfa, and ctsc at 7 dpi, respectively. mpeg1 was used to label all MC cells. The blue boxed region is highlighted in the zoom-in image to the right. Scale bar = 50 μm. A stands for arium, V stand for ventricle and OFT stands for outflow tract. White dashed lines outline the heart and the yellow dashed lines indicate approximate resection plane.",
    "ncbi_link": "cd74a: 58113
ctsc: 368704
mpeg1: 335407
tnfa: 405785"
  },
  {
    "caption": "F, In situ hybridization showing temporal spatial expression patterns of postnb. The white boxed region is shown in zoom-in images at the bottom. Scale bar = 25 μm. White dashed lines outline the heart and the yellow dashed lines indicate approximate resection plane. A stands for arium, V stand for ventricle and OFT stands for outflow tract.",
    "ncbi_link": "postnb: 337176"
  },
  {
    "caption": "H, Fluorescent in situ hybridization for postnb, tnfα, and tnfrsf1a in the injury area at 7 dpf, respectively. The white boxed regions are shown in their respective zoom-in images to the right. White dashed lines outline cardiac apex and the yellow dashed lines indicate approximate resection plane. Scale bar = 25 μm.",
    "ncbi_link": "postnb: 337176
tnfα: 405785
tnfrsf1a: 406471"
  },
  {
    "caption": "J, Violin plots showing expression of cxcl18b, sele, atf3, and fosl1a in each eEC subpopulation.",
    "ncbi_link": "atf3: 393939
cxcl18b: 795785
fosl1a: 564241
sele: 558139"
  },
  {
    "caption": "K, Fluorescent in situ hybridization for fosl1a at 7 dpi. The white boxed region is shown in a higher magnification image to the right for the injury area. cdh5 was used to label all EC cells and the red boxed region is shown in a higher magnification image to highlight a pan-EC cdh5 expression in green. White dashed lines outline the heart and the yellow dashed lines indicate approximate resection plane. Scale bar = 25 μm. A stands for arium, V stand for ventricle and OFT stands for outflow tract.",
    "ncbi_link": "cdh5: 445471
fosl1a: 564241"
  },
  {
    "caption": "A, Wildtype or kit mutant stained with AFOG at 14 days and 30 dpi. Sham-operated zebrafish hearts serve as control. Scale bar = 100 μm.",
    "ncbi_link": "kit: 30256"
  },
  {
    "caption": "D, F, Violin plots showing the expression of il1b in MC1 (D), and ctsd expression in MC (F). E, G, Expression of il1b (E) and ctsd (G) in WT and kit mutant hearts determined by qRT-PCR.",
    "ncbi_link": "ctsd: 65225
il1b: 405770
kit: 30256"
  },
  {
    "caption": "O, Violin plots showing expression of junba in eEC. P, Expression of junba in WT and kit mutant hearts determined by qRT-PCR.",
    "ncbi_link": "junba: 407086
kit: 30256"
  },
  {
    "caption": "C T98G cells were treated with non-targeting (CTRL) or KU70-targeting siRNAs prior to whole cell extract preparation, and pull-down as in B. Inputs and eluates were analyzed by WB using indicated antibodies.",
    "ncbi_link": "KU70: 2547"
  },
  {
    "caption": "A T98G cells stably expressing cGAS (T98GcGAS) or not (T98GEmpty) were transfected or not with dsDNA for 6 h prior to whole cell extraction and WB analysis using indicated antibodies.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "C T98GEmpty and T98GcGAS were transfected or not with biotinylated dsDNA prior to whole cell extraction and pull-down using streptavidin-affinity beads. Inputs and eluates were analyzed by WB using indicated antibodies.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "J T98GcGAS were transfected or not with dsDNA in presence or not of NU7441, prior to WB analysis using indicated antibodies.",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "F T98GEmpty and T98GcGAS stably expressing a GFP reporter (T98G-GFPEmpty and T98G-GFPcGAS, respectively) were xenotransplanted into the head of tg(mfap4:RFP) zebrafish line at 3 days post fertilization (dpf). Zebrafish embryos were imaged daily over 3 days. The graph represents the mean (±SEM) percentage of tumor growth normalized by the area on the day of transplantation (n=21 T98G-GFPEmpty and n=29 T98G-GFPcGAS embryos).",
    "ncbi_link": "GFP: 
RFP: 
cGAS: 115004
mfap4: 405825"
  },
  {
    "caption": "A Graph represents the mean (± SEM) fold migration of THP-1 cells through a 3 µm transwell insert when conditioned media from T98GEmpty or T98GcGAS was applied to lower chamber for 6 h. CCL2 was used as positive control (n=8 biological replicates).",
    "ncbi_link": "cGAS: 115004"
  },
  {
    "caption": "E Graph presents the quantification of macrophages recruited at tumor site 24 h post xenotransplantation in D (n=21 T98G-GFPEmpty and n=29 T98G-GFPcGAS embryos).",
    "ncbi_link": "GFP: 
cGAS: 115004"
  },
  {
    "caption": "H Violin plots present the expression of PRKDC and MB21D1 in datasets analyzed in A, based on tumor grade (II to IV).",
    "ncbi_link": "MB21D1: 115004
PRKDC: 5591"
  },
  {
    "caption": "F. Relative mRNA expression  of IL-22, IL-17a, IFN-γ, IL-1β, IL-6, IL-10, Muc1  of colon  tumour described in (A) was shown. Data information: All data are mean ± s.e.m. NS, not significant. *P < 0.05, **P < 0.01, ****P < 0.0001 based on two-tailed Student's t test Each dot represents one mouse, n=15. Data are representative of three biological replicates.",
    "ncbi_link": "IFN-γ: 15978
IL-10: 16153
IL-17a: 16171
IL-1β: 16176
IL-22: 50929
IL-6: 16193
Muc1: 17829"
  },
  {
    "caption": "representative histological  images (B) of wild-type control mice  or BTNL2-KO mice  treated with 2% DSS  for 8 days were shown (n=15).",
    "ncbi_link": "BTNL2: 547431"
  },
  {
    "caption": "E. Relative mRNA expression  of  IL-22, RegⅢγ, RegⅢβ, Muc1, IL-17a,  IFN-γ, IL-1β, IL-6 and  IL-10 of colonic  tissues described in (A) was shown. Data information: All data are mean ± s.e.m. NS, not significant. **P < 0.01, ***P < 0.001, ****P < 0.0001 based on two-tailed Student's t test Each dot represents one mouse, n=15. Data are representative of three biological replicates.",
    "ncbi_link": "IFN-γ: 15978
IL-10: 16153
IL-17a: 16171
IL-1β: 16176
IL-22: 50929
IL-6: 16193
Muc1: 17829
RegⅢβ: 18489
RegⅢγ: 19695"
  },
  {
    "caption": "representative H&E images (H) of wild-type control mice  or BTNL2-KO mice  treated with Fc or mIL-22-Fc (ip. 5 μg/mouse) at day 0, 2, 4, 6 during 2% DSS  treatment were shown (n=12). Data information Data are representative of three biological replicates H).",
    "ncbi_link": "BTNL2: 547431"
  },
  {
    "caption": "G. IL-22, IL-17a, RORC  and HIF-1α expression in splenocytes  after cultured in plate-coated Fc or mBTNL2-Fc (30 μg/mL) for 20 h was analyzed by  real-time PCR. Data information: All data are mean ± s.e.m. NS, not significant., *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 based on two-tailed Student's t test Each dot represents one repetition, n=6 Data are representative of three biological replicates",
    "ncbi_link": "HIF-1α: 15251
IL-17a: 16171
IL-22: 50929
RORC: 19885"
  },
  {
    "caption": "E. Relative mRNA expression  of IL-22, RegⅢγ, RegⅢβ, Muc1,  IL-17a,  IFN-γ, IL-1β and IL-6 from colonic  tissues described in (A) was shown. Data information: All data are mean ± s.e.m. NS, not significant., *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 based on two-tailed Student's t test Each dot represents one repetition, n=15 Pooled data from three biological replicates",
    "ncbi_link": "IFN-γ: 15978
IL-17a: 16171
IL-1β: 16176
IL-22: 50929
IL-6: 16193
Muc1: 17829
RegⅢβ: 18489
RegⅢγ: 19695"
  },
  {
    "caption": "J. Relative mRNA expression  of IL-22, RegⅢγ, RegⅢβ, Muc1,  IL-17a, IFN-γ,  IL-1β and  IL-6 of colonic  tissue described in (F) was shown. Data information: All data are mean ± s.e.m. NS, not significant., *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 based on two-tailed Student's t test Each dot represents one repetition, n=12 Pooled data from three biological replicates",
    "ncbi_link": "IFN-γ: 15978
IL-17a: 16171
IL-1β: 16176
IL-22: 50929
IL-6: 16193
Muc1: 17829
RegⅢβ: 18489
RegⅢγ: 19695"
  },
  {
    "caption": "F. Relative mRNA expression  of IL-22,  IL-17a,  IFN-γ, IL-1β, IL-6, IL-10 and Muc1  of colonic  tumour described in (A) was shown. Data information: All data are mean ± s.e.m. NS, not significant., *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 based on two-tailed Student's t test for F, Each dot represents one mouse, n=12. Pooled data from three biological replicates",
    "ncbi_link": "IFN-γ: 15978
IL-10: 16153
IL-17a: 16171
IL-1β: 16176
IL-22: 50929
IL-6: 16193
Muc1: 17829"
  },
  {
    "caption": "(A Representative confocal images of HeLa and TRIM16KO cells treated with (A) MG132 (20 µM, 2h), scale bar: 7.5 µm. and the samples were processed for IF analysis with Ub and p62 antibody. (B Representative confocal images of control siRNA and TRIM16 siRNA transfected cells treated with (B) MG132 (20 µM, 2h), where IF analysis was conducted with Ub and p62 antibodies. (C The graph shows the the percentage of cells with Ub-p62 co-localized dots. Data from ≥10 fields (40X), n=3, Mean ±SD, **p < 0.0003, *p < 0.002 (Student's unpaired t-test). Data information: Unless otherwise stated, scale bar: 10 µm.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "D) Representative confocal images of HeLa and TRIM16KO cells treated with (D) H2O2 (200 µM, 2h) and the samples were processed for IF analysis with Ub and p62 antibody. E) Representative confocal images of control siRNA and TRIM16 siRNA transfected cells treated with (E) H2O2, (200 µM, 2h), where IF analysis was conducted with Ub and p62 antibodies. F) The graph shows the the percentage of cells with Ub-p62 co-localized dots. Data from ≥10 fields (40X), n=3, Mean ±SD, **p < 0.0003, *p < 0.002 (Student's unpaired t-test). Data information: Unless otherwise stated, scale bar: 10 µm.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(G) Western blot (WB) analysis of detergent-soluble and -insoluble fractions of HeLa and TRIM16KO cells treated with MG132 (50 µM, 1h) and probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(J) Representative confocal images of HeLa and TRIM16KO cells treated with MG132 (20 µM, 2h) and processed for IF analysis with Ub and LC3B antibody.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(K, L) WB analysis of LC3B levels in lysates of HeLa and TRIM16KO cells treated with (K) Bafilomycin A1 (300 nM, 3h) alone or (L) with MG132 (10 µM, 4h) as indicated. L.E, Low exposure; H.E, high exposure.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(M) Representative confocal images HeLa and TRIM16KO cells treated with H2O2 (200 µM, 2h) and processed for IF analysis with Proteostat dye, Ub, and p62 antibody. To show the cellular details, the brightness of TRIM16KO cells images was increased more than control cells",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(A) Western blot analysis of HeLa and TRIM16KO cell lysates probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(B) Western blot analysis of lysates from HeLa and TRIM16KO cells treated with or without MG132 and probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(C) Left panel, western blotting with HeLa and TRIM16KO cell lysates probed with indicated antibodies. Right panel, densitometric analysis (mean ±SD) of protein band intensity relative to actin, n=3, ***p < 0.0005 (Student's unpaired t-test).",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "D-G (D, F) HEK293T cells were either transiently transfected with an empty vector or a Flag-tagged-TRIM16 expressing vector and immunoblotted with Flag or indicated antibodies. L.E, Low exposure; H.E, High Exposure. (E, G) Densitometric analysis (mean ±SD) of protein band intensity relative to actin, n=3, *p < 0.05 (Student's unpaired t-test).",
    "ncbi_link": "Flag: 
TRIM16: "
  },
  {
    "caption": "(H) WB analysis of HeLa and TRIM16KO lysates of cells treated with cycloheximide (100 µM) for the indicated period and probed with different antibodies as indicated. The blots of control and TRIM16KO cells are exposed for the equal duration and developed together on the same X-ray film. (I) Quantification of NRF2, p62, and KEAP1 band intensities relative to actin. n=3, **p < 0.005, *p < 0.05 (Student's unpaired t-test).",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(A, B) Co-IP analysis of the interaction between NRF2 and KEAP1 in absence and presence of TRIM16.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(D) Co-IP analysis of the interaction between KEAP1 and p62 in absence and presence of TRIM16.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(A-C) Analysis of NRF2 ubiquitination in absence and presence of TRIM16 by Co-IP assays using transiently transfected plasmid constructs as indicated. Two different variants of ubiquitin protein are used, one that can only be ubiquitinated at Lysine 48 residue (HA-K48-UB) and other that can be only ubiquitinated at Lysine 63 residue (HA-K63-UB). All other lysine residues are mutated. L.E, Low exposure; H.E, High Exposure.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Analysis of NRF2 ubiquitination in absence and presence of TRIM16 by Ni-NTA pull-down assays using transiently transfected plasmid constructs as indicated. His-tagged ubiquitin which is mutated at all lysines except 63 position is used in these assays.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Analysis of NRF2 ubiquitination in absence and presence of TRIM16 by Ni-NTA pull-down assays using transiently transfected plasmid constructs as indicated. His-tagged ubiquitin which is mutated at all lysines except 63 position is used in these assays.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(F) Analysis of NRF2 ubiquitination in absence and presence of TRIM16 deletion variants by Co-IP assays using transiently transfected plasmid constructs as indicated.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(G) Western blot analysis of lysates from HeLa, TRIM16KO cells and TRIM16KO cells complemented with TRIM16 deletion constructs where cells were treated with MG132 (20 µM, 2h) and the blot is probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(H) Western blot analysis of lysates from HeLa, TRIM16KO cells and TRIM16KO cells complemented with TRIM16 deletion constructs where cells were treated with MG132 (20 µM, 2h) and the blot is probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(A) Western blot analysis of HeLa and TRIM16KO lysates of cells treated with increasing concentrations of H2O2 as specified and probed with antibodies as indicated.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(B) WB analysis of HeLa and TRIM16KO lysates of cells treated with 400 µM of H2O2 for different durations as indicated and probed with antibodies as shown. The red arrows indicate the time point where the cells were retreated with 400 µM of H2O2. L.E, Low exposure; H.E, High Exposure.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(D) WB analysis of HeLa and TRIM16KO lysates of cells treated with 2.5 µM (2 h) of As2O3.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(E-G) RNA isolated from HeLa and TRIM16KO cells, untreated or treated with MG132 (20 µM, 2h) were subjected to qRT-PCR with primers of genes as indicated. The fold induction in MG132 treated samples is calculated relative to untreated samples. Mean ±SD, n=3, *p < 0.05, **p < 0.005 (Student's unpaired t-test).",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "RNA isolated from control and NRF2 knockdown HeLa cells transfected with control vector or Myc-TRIM16 subjected to qRT-PCR with primers of genes as indicated. Mean ±SD, n=3, **p < 0.005, ***p < 0.0005 (Student's unpaired t-test).",
    "ncbi_link": "Myc: 
NRF2: 4780
TRIM16: 10626"
  },
  {
    "caption": "RNA isolated from control and NRF2 knockdown HeLa cells transfected with control vector or Myc-TRIM16 subjected to qRT-PCR with primers of genes as indicated. Mean ±SD, n=3, **p < 0.005, ***p < 0.0005 (Student's unpaired t-test).",
    "ncbi_link": "Myc: 
NRF2: 4780
TRIM16: 10626"
  },
  {
    "caption": "(K) Western blot analysis of HeLa and TRIM16KO lysates of cells treated with h increasing concentrations of H2O2 as specified and probed with antibodies as indicated.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(M) Representative confocal images of control, Ubb and Ube2n siRNA transfected cells treated with H2O2 (200 µM, 2h) and IF was performed with Ub and p62 antibodies. Scale bar: 10 µm.",
    "ncbi_link": "Ubb: 7314
Ube2n: 7334"
  },
  {
    "caption": "(O) Western blot analysis of Ubb and Ube2n siRNA transfected cell lysates with antibodies as indicated.",
    "ncbi_link": "Ubb: 7314
Ube2n: 7334"
  },
  {
    "caption": "(A) Control or NRF2 siRNA transfected HeLa cells lysates were subjected to western blotting with indicated antibodies.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "(B, C) RNA isolated from untreated or MG132-treated (20 µM, 2h) control or NRF2 siRNA transfected cells were subjected to qRT-PCR with primers of genes as indicated. The fold induction in MG132 treated samples is calculated relative to untreated samples. Mean ±SD, n=3, *p < 0.05 (Student's unpaired t-test). Data information: Unless otherwise stated, scale bar: 10 µm.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "WB analysis of control siRNA or NRF2 siRNA transfected lysates of HeLa cells, untreated or treated with MG132 (20 µM, 2h) as indicated and probed with antibodies as shown. L.E, Low exposure; H.E, High Exposure.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "WB analysis of control siRNA or NRF2 siRNA transfected lysates of HeLa cells, untreated or treated with H2O2 (200 µM, 2h) as indicated and probed with antibodies as shown. L.E, Low exposure; H.E, High Exposure.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "Left panels: Representative confocal images of control siRNA and NRF2 siRNA transfected cells treated with (F) MG132 (20 µM, 2h), where IF was conducted with Ub and p62 antibodies. Right panels: fluorescence intensity line tracing corresponding to a white line in zoom panel.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "Left panels: Representative confocal images of control siRNA and NRF2 siRNA transfected cells treated with (G) H2O2 (200 µM, 2h), where IF was conducted with Ub and p62 antibodies. Right panels: fluorescence intensity line tracing corresponding to a white line in zoom panel.",
    "ncbi_link": "NRF2: 4780"
  },
  {
    "caption": "(H) Hela cells, TRIM16KO cells, and TRIM16KO cells complemented with Myc-NRF2 or GFP-NRF2 were treated with MG132 (20 µM, 2h) and subjected to WB analysis with Myc, GFP and indicated antibodies.",
    "ncbi_link": "GFP: 
Myc: 
NRF2: 4780
TRIM16: 10626"
  },
  {
    "caption": "(I) Representative confocal images of Hela cells, TRIM16KO cells, and TRIM16KO cells complemented with Myc-NRF2 which were treated with MG132 (20 µM, 2h) and subjected to IF with Ub and p62 antibodies.",
    "ncbi_link": "Myc: 
NRF2: 4780
TRIM16: 10626"
  },
  {
    "caption": "WB analysis of detergent-soluble and -insoluble fractions of HeLa and TRIM16KO cells expressing either (A) Flag-p62 probed with Flag or indicated antibodies. L.E, Low exposure; H.E, High Exposure. Densitometric analysis of WB's normalized with α-Tubulin or Lamin-B1.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "WB analysis of detergent-soluble and -insoluble fractions of HeLa and TRIM16KO cells expressing either (C) GFP-polyQ74 probed with or GFP or indicated antibodies. L.E, Low exposure; H.E, High Exposure. Densitometric analysis of WB's normalized with α-Tubulin or Lamin-B1.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(H) Co-IP analysis of the interaction between two differently tagged TRIM16 variants.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(I) WB analysis of detergent-soluble and -insoluble DSS-cross-linked fractions of HeLa and TRIM16KO cells, untreated or treated with MG132 (10 µM, 4h) and probed with indicated antibodies.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(J) Co-IP analysis of the interaction between Flag-tagged TRIM16 and Myc-tagged TRIM16 full length and its domain deletion proteins.",
    "ncbi_link": "Flag: 
Myc: 
TRIM16: 10626"
  },
  {
    "caption": "(A) MTT assays performed at different time points with HeLa and TRIM16KO cells, untreated or treated with H2O2 (400 µM, 2h). Data, mean ±SD, n=3, *p < 0.05 (Student's unpaired t-test).",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(B) Images of HeLa and TRIM16KO cells, untreated or treated with As2O3 (2.5 µM, 4h). Scale bar: 400 µm.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Flow cytometry analysis of HeLa and TRIM16KO cells stained with Annexin-V/Propidium Iodide (double staining), untreated or treated with (C) As2O3 (2.5 µM, 4h)",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Flow cytometry analysis of HeLa and TRIM16KO cells stained with Annexin-V/Propidium Iodide (double staining), untreated or treated with (D) H2O2 (400 µM, 2h)",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Flow cytometry analysis of HeLa and TRIM16KO cells stained with Annexin-V/Propidium Iodide (double staining), untreated or treated with (E) puromycin (5 µg/ml, 6h)",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "Flow cytometry analysis of HeLa and TRIM16KO cells stained with Annexin-V/Propidium Iodide (double staining), untreated or treated with (F) MG132 (20 µM, 8h).",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(G) Immunoblot blot analysis of HeLa and TRIM16KO lysates of cells treated with 5 µM of As2O3 for different durations as indicated and probed with antibodies as shown. L.E, Low exposure; H.E, High Exposure. Arrowheads indicate the cleaved form of PARP-1 and Casapse-3.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(A, B) Clonogenic assays were performed with HeLa and TRIM16KO cells, untreated or treated with As2O3 or MG132.",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(C) Tumor volumes of HeLa and TRIM16KO tumors at indicated time points. As2O3 is injected when tumor volume of all groups was >100mm3 (day 0 in the graph). Tumor volumes were measured on an interval as indicated. Mean ±SE, n=6 (each group), *p < 0.05, **p < 0.005, ***p < 0.0005 (ANOVA). (D) Graph shows the % tumor regression (Tumor volume on day 1 of As2O3 treatment / Tumor volume on day of sacrifice X 100). Mean ±SE, n=6 (each group), **p < 0.005 (Student's unpaired t-test). ",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(E) Representative images of HeLa and TRIM16KO tumors formed in the nude mice in the absence and presence of As2O3. (F) Representative pictures of dissected tumors. ",
    "ncbi_link": "TRIM16: 10626"
  },
  {
    "caption": "(B)  flg22-induced ROS production in Col-0 and fer-4 mutant roots  under  Pi-starvation conditions. Seedlings grown in either HP or LP media were treated with 1 μM  flg22, RALF23 or both  flg22 and RALF23 for 15 mins. Roots were harvested and stained with H2DCFDA. One representative root was shown. (C) Average H2DCFDA signal intensity in roots shown in (B). The fluorescence intensity was quantified with ImageJ. The data shown indicate the means ± SDs (n = 30, n refers to the number of  roots per group); n.s., not significant; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results. ",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "(F)  RALF23 inhibits flg22-induced MAMP-responsive  FRK1 gene expression in a Pi  content-dependent manner. Seedlings  grown in either  HP or LP  media were treated with water or  flg22 for 15 mins and roots were harvested. The relative  expression of FRK1  was quantified via  RT-qPCR. The data shown indicate the means ± SDs (n = 3, n refers to technical replicates); n.s., not significant; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results. ",
    "ncbi_link": "FRK1: 816436
RALF23: 820907"
  },
  {
    "caption": "(A) The PSR induces the cleavage of  PRORALF23-GFP into mature  RALF23-GFP. The 35S promoter-driven RALF23-GFP line was grown in either HP  or LP media for 5 days and roots were harvested. Premature and mature  RALF23 levels were determined with anti-GFP. β-actin  was used as a loading control. Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "GFP: 
RALF23: 820907"
  },
  {
    "caption": "(E) The PSR activates RALF expression  in a PHR1-dependent manner. Col-0  and phr1 seedlings were grown in LP media for 5 days and roots  were harvested. The relative  expression of RALFs was quantified via  RT-qPCR. The data shown indicate the means ± SDs (n = 3, n refers to technical replicates); n.s., not significant; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "PHR1: 828979
phr1: 828979"
  },
  {
    "caption": "(G) PHR1  directly binds to RALF promoters, as shown via ChIP-PCR. The  Myc-labelled PHR1  overexpression line was immunoprecipitated  with anti-Myc. ChIP  analysis was performed on Col-0, CRY1-Myc and PHR1-Myc transformed plants, with Col-0 and CRY1-Myc transformed plants as negative controls. The data shown indicate the means ± SDs (n = 3, n refers to technical replicates); n.s., not significant; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "Myc: 
CRY1: 826470
PHR1: 828979"
  },
  {
    "caption": "(B) PHR1 negatively regulates FLS2-BAK1 complex formation under  Pi-starvation conditions. Col-0,  phr1 mutant seedlings  were grown in either  HP or LP  media for 5 days, then lysing roots into  protoplasts, transformed with water or  PHR1-Myc plasmid and treated with flg22 for 6 hours. The amount of immunoprecipitated FLS2  and coimmunoprecipitated BAK1 were determined using anti-FLS2 and anti-BAK1 antibodies, respectively. Preimmune serum (IgG) was used as negative control. Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "Myc: 
phr1: 828979
PHR1: 828979"
  },
  {
    "caption": "(D) Application of  RALF23/34 disrupted FLS2-BAK1 complex formation in phr1 mutants. phr1 mutants grown in  LP media were treated with water, 1 μM flg22, 1 μM RALF23, 1 μM RALF34 or both flg22  and RALF for 6 hours. The amount of immunoprecipitated FLS2 and  coimmunoprecipitated BAK1 were determined using anti-FLS2 and anti-BAK1 antibodies, respectively. IgG was used as a negative control. Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "phr1: 828979"
  },
  {
    "caption": "(E)  RALF23/34 promoted the  growth  of  Pto DC3000 in phr1  mutants. Col-0 and phr1 mutant seedlings grown in LP  media were  root  inoculated (by soaking) with a bacterial suspension (OD600 = 0.2) for 2 min, and the number of bacteria from individual root was quantified at 5 dpi. The data shown indicate the means ± SDs (n = 18, n refers to the number of  roots  per group). The different lowercase letters indicate statistical significance (one-way ANOVA). Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "phr1: 828979"
  },
  {
    "caption": "(F) FER negatively regulates FLS2-BAK1  complex formation under Pi-starvation conditions. Col-0, fer-4  mutant and FER/fer-4  complementation lines seedlings  were grown in either HP or LP  media for 5 days and treated with  flg22 for 6 hours. The amount of  immunoprecipitated FLS2  and coimmunoprecipitated BAK1 was determined using anti-FLS2 and anti-BAK1 antibodies, respectively. Preimmune serum (IgG) was used as a negative control. Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "FER: 824318
fer-4: 818622"
  },
  {
    "caption": "(C) Pto DC3000  and B. subtilis upregulate  phosphate  absorption gene expression. Col-0, phr1  and  fer-4  mutant roots  were harvested 48 hours after inoculation with Pto DC3000 or B. subtilis  in Pi-sufficient or Pi-deficient condition, and the relative expression  of Pi-absorbing genes was quantified via RT-qPCR. The data shown indicate the means ± SDs (n = 3, n refers to technical replicates); *, p < 0.05; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "fer-4: 818622
phr1: 828979"
  },
  {
    "caption": "The fer-4 rhizosphere microbiome promotes plant growth and alleviates LP stress. Arabidopsis seeds were germinated on 1/2-strength MS media for 3 days and then transplanted to either HP or LP media for another 5 days. The seedlings were then transferred to vermiculite and inoculated with Col-0 or fer-4 rhizosphere microbiomes. (B), Images were taken 4 weeks after inoculation. Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "(D) The  fer-4 rhizosphere microbiome  upregulated phosphate absorption  gene expression. The roots  of Col-0 were harvested after 4 weeks of inoculation with the Col-0 or  fer-4 rhizosphere microbiome  under LP  condition, and the relative  expression  of  Pi-absorbing genes was quantified via RT-qPCR. The data shown indicate the means ± SDs (n = 3, n refers to technical replicates); n.s., not significant; *, p < 0.05; **, p < 0.01 (Student's t test). Data information: All experiments were repeated three times with similar results.",
    "ncbi_link": "fer-4: 818622"
  },
  {
    "caption": "A FBN2 mRNA levels in multiple human tissues. Human tissue cDNAs were used as templates for PCR of FBN2, followed by agarose gel analyses. GAPDH levels served as loading controls (biological replicates, n=2).",
    "ncbi_link": "FBN2: 2201
GAPDH: 2597"
  },
  {
    "caption": "B FBN2 mRNA levels in mouse tissues based on quantitative RT-PCR. Data were normalized based on levels in adipose tissues.",
    "ncbi_link": "FBN2: 14119"
  },
  {
    "caption": "C Comparison of FBN2 transcript levels between human and mouse placentas. Common primers for FBN2 and GAPDH in both species were used for RT-PCR analyses (biological replicates, n=3) .",
    "ncbi_link": "GAPDH: 
FBN2: 2201
FBN2: 14119"
  },
  {
    "caption": "F For prokaryotic cell expression, a cDNA fragment corresponding to residues 2779 to 2912 of the human FBN2 coding region was appended with GST and 6-histidine tags and sub-cloned into the PGEX-6P-1 vector for expression in E. coli. Left panel: Coomassie blue staining of proteins in the SDS-PAGE gel before and after digestion with the PreScission protease. 1: Flow through; 2: Washes; 3: Before PreScission treatment; 4: After PreScission treatment. Right panel: Immunoblotting using placensin antibodies.",
    "ncbi_link": "FBN2: 2201"
  },
  {
    "caption": "B Placensin stimulation of glucose secretion (at 5h) and key gluconeogenesis gene transcripts (at 1h) in both cell types (biological replicates, n=4). Transcript levels for PEPCK and G6Pase were determined using quantitative RT-PCR. Treatment with glucagon (10 nM) served as positive controls.",
    "ncbi_link": "G6Pase: 14378///14377///68401
PEPCK: 107690"
  },
  {
    "caption": "B Knockdown of FBN2 in HTR-8/SVneo cells led to decreases in FBN2 transcripts and placensin secretion. Cells were treated with FBN2 siRNA (SiFBN2; 20 nM) or control siRNA (SiC; 20 nM) for 6h. Following media change, cells and conditioned media were collected at 48h after incubation. Placensin transcripts and proteins were determined by RT-PCR and ELISA (biological replicates, n=8), respectively. Lower panel: immunoblotting of secreted placensin by HTR-8/Svneo.",
    "ncbi_link": "FBN2: 2201"
  },
  {
    "caption": "D Placensin stimulation of transcript levels for MMP9 but not MMP2(biological replicates, n=12). Cells were treated with placensin for 24h before RT-PCR analyses of transcript levels.",
    "ncbi_link": "MMP2: 4313
MMP9: 4318"
  },
  {
    "caption": "B, C Colony-forming assays in H1299 (B) and A549 (C) lung cancer cells after knockdown by shRNA lentiviral constructs designed against DDX3 or vector control. Corresponding immunoblots displaying knockdown levels of DDX3. Mean from 3 replicates with SD.",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "D Proliferation of A549 and H1299 cells after knockdown of DDX3. Mean from 3 replicates with SD. (A549 P = 0.011, H1299 P = 0.014; exponential curve fit, extra sum of squares F-test).",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "E β-galactosidase staining in parental A549 cells and A549 DDX3 knockdown cells displaying senescent cells identified by the blue color.",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "K Survival analysis of lung cancer patients in low and high DDX3 expressing tumors (Kaplan-Meier curve and log-rank test, P = 0.016).",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "Confirmation of high expression of Twist1 and DDX3 in the lung tumors of the transgenic Twist1/KrasG12D mouse. Scale bar is 100 μm.",
    "ncbi_link": "Kras: 16653
Twist1: 22160"
  },
  {
    "caption": "Micro-CT images of transgenic Twist1/KrasG12D mice treated as in (C), before treatment and 1 week after treatment. Tumors are indicated by arrows and confirmed by H&E staining of lung sections (lower panel). Scale bar is 250 μm.Quantification of tumor volume measured by micro-CT in Twist1/KrasG12D mice, as shown in (D). Significance was assessed by two-sided, unpaired t-test. Error bars represent SD.",
    "ncbi_link": "Kras: 16653
Twist1: 22160"
  },
  {
    "caption": "Micro-CT images of transgenic Twist1/KrasG12D mice treated as in (H), before treatment and 1 week after treatment.Quantification of tumor volume measured by micro-CT in Twist1/KrasG12D mice, as shown in (I) and expressed as relative tumor size. Significance was assessed by two-sided, unpaired t-test. Error bars represent SEM.",
    "ncbi_link": "Kras: 16653
Twist1: 22160"
  },
  {
    "caption": "A Cell cycle analysis of H1299 cells treated with shDDX3 and processed by flow cytometry. Knockdown of DDX3 led to a decrease of cells in S-phase and an increase of cells in G1-phase, indicative of a G1 arrest. Significance was assessed by two-sided, unpaired t-test. Error bars represent SD.",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "A β-catenin (red) and DDX3 (green) expression in H1299 cells. After overexpressing β-catenin, both DDX3 and β-catenin accumulate in the nucleus. Scale bar is 10 μm.",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": "D, E β-catenin/TCF4 activity was determined by the TOP/FOP reporter assay. Co-transfection with β-catenin is indicated below.",
    "ncbi_link": "β-catenin: 1499
TCF4: 6925"
  },
  {
    "caption": "F-I H1299 and A549 cells were treated with RK-33 (0, 1, 2, and 3 μM) and co-transfected with β-catenin in (F, H). Treatment with RK-33 decreased TCF4 activity in both cell lines.",
    "ncbi_link": "TCF4: 6925"
  },
  {
    "caption": "J, K Normalized mRNA expression of TCF4-regulated proteins (Axin-2, c-Myc, Cyclin D1) and DDX3 were measured by qRT-PCR in H1299 cells after knockdown of DDX3 (J) and treatment with RK-33 (K). All experiments were repeated three times.",
    "ncbi_link": "Axin-2: 8313
Cyclin D1: 595
DDX3: 1654
c-Myc: 4609
TCF4: 6925"
  },
  {
    "caption": "D H1299 cells, containing a stable non-homologous end-joining (NHEJ) reporter construct, were treated with RK-33 and knockdown of DDX3. Reporter construct expressed GFP, which was quantified by flow cytometry. All experiments were repeated three times.",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "E Microarray results from MDA-MB-231 cells treated with RK-33 and shDDX3 were validated by qRT-PCR using NHEJ Mechanisms of DSBs Repair PrimePCR plates (Bio-Rad) and performed in biological triplicates.",
    "ncbi_link": "DDX3: 1654"
  },
  {
    "caption": "(A) GFP time-lapse images of neonatal rat cardiomyocytes expressing EGFP-CLIP-170 WT 0 min and 15 min after treatment with 20 μM Compound C (left side panel) and expressing EGFP-CLIP-170 S311A (right side panel). Higher magnification of white square (upper row) showing CLIP-170 migrated longitudinally toward the cell-cell junctions.",
    "ncbi_link": "EGFP: 
CLIP-170: 56430"
  },
  {
    "caption": "(B) Beeswarm plots of comet length of EGFP-CLIP-170. The comet length from multiple cells in different fields was analyzed. Number of comets analyzed, Pre: n=32, Cpd. C: n=36, CLIP S311A: n=68. Data means ±S.D. Differences among multiple groups were compared by one-way ANOVA, followed by a post hoc comparison using the Tukey method. **, P<0.01 versus Pre.",
    "ncbi_link": "CLIP: 56430"
  },
  {
    "caption": "(C) GFP time-lapse images of neonatal rat cardiomyocytes expressing EGFP-CLIP-170 WT treated with control siRNA (siCL, left) or siRNA targeting both AMPKα1 and α2 (siAMPKα1α2, right). White dotted lines in the images showed the connected cardiomyocyte not expressing EGFP-CLIP-170 WT.",
    "ncbi_link": "AMPKα1: 65248"
  },
  {
    "caption": "(D) Beeswarm plots of comet length of EGFP-CLIP-170. The comet length from multiple cells from different fields was analyzed. Number of comets analyzed, siCL: n=178, siAMPKα1α2: n=184. Data means ±S.D. Two-tailed Student's t-test was used to analyze differences between two groups. **, P<0.01 versus siCL.",
    "ncbi_link": "AMPKα1: 65248"
  },
  {
    "caption": "(C) Box and whisker plots of the cell size of a cardiomyocyte 2 hours after treatment with or without 2 μM MYK-461, showing the 25th percentile (bottom line of each box), median (middle line of each box), 75th percentile (top line of each box), maximum and minimum (each whisker). Adenovirus expressing EGFP-CLIP-170 (adCLIP) mutant was used (WT, S311A, S311D). Numbers in the graph indicate n number of the cells from 2 independent experiments. Control (-/-): n=784, MYK-461: n=939, CLIP WT: n=656, CLIP WT + MYK-461: n=619, CLIP S311A: n=405, CLIP S311A + MYK-461: n=635, CLIP S311D: n=613, CLIP S311D + MYK-461: n=735. Data means ±S.D. Differences among multiple groups were compared by one-way ANOVA, followed by a post hoc comparison using the Tukey method. **, P<0.01 versus Control, ††, P<0.01 versus CLIP WT, n.s., not significant.",
    "ncbi_link": "EGFP: 
CLIP: 56430
CLIP-170: 56430"
  },
  {
    "caption": "(A) Beeswarm plots of the echocardiographic parameter (ejection fraction) of individual Cre control (CLIP-170 S311A +/+; α-MHC-MerCreMer+/−), Control mice (CLIP-170 S311A flox/+; α-MHC-MerCreMer−/−), and CLIP-170 S311A overexpressing mice (CLIP-170 S311A flox/+; α-MHC-MerCreMer+/−), before (Pre), 2 weeks (Tx2w), 8 weeks (Tx8w), 26 weeks (Tx26w) and over 1 year (Tx1y) after tamoxifen induction. Number of mice, (Cre control, Control, S311A), Pre (6, 2, 3), Tx 2w (9, 5, 5), Tx 8w (9, 10, 14), Tx1 2w (7, 10, 14), Tx 26w (3, 7, 8), Tx 52w (3, 7, 9).",
    "ncbi_link": "CLIP-170: 56430
Cre: 2777477
Mer: 17289
α-MHC: 17888"
  },
  {
    "caption": "(B) Beeswarm plots of another line of CLIP-170 S311A overexpressing mice (line 9). Number of mice, (Control, S311A), Pre (7, 3), Tx 2w (4, 7), Tx 8w (6, 4), Tx 12w (5, 4), Tx 52w (3, 3). Data means ±S.D. Statistical significance was determined by two-way ANOVA followed by post hoc Tukey's multiple comparison test. ##: p < 0.01 vs Duration-matched Cre Control, *: p < 0.05, **: p < 0.01 vs Duration-matched Control; †: p < 0.05, ††: p < 0.01, S311A TG mice 12 weeks vs 52 weeks.",
    "ncbi_link": "CLIP-170: 56430
Cre: 2777477"
  },
  {
    "caption": "(C) Representative long axis four-chamber cardiac magnetic resonance images of CLIP-170 S311A TG mice and control mice over 1 year after tamoxifen induction. Left column showed systole images and right column represented diastole images. Three mice from each group were analyzed for cardiac MRI. The representative images were shown.",
    "ncbi_link": "CLIP-170: 56430"
  },
  {
    "caption": "(E) Beeswarm plots of the echocardiographic parameter (ejection fraction) from CLIP-170 S311D overexpressing mice and the control. Number of mice, (Control, S311D), Tx 2w (3, 4), Tx 8w (5, 11), Tx 26w (4, 11). Data means ±S.D. There was no significant difference.",
    "ncbi_link": "CLIP-170: 56430"
  },
  {
    "caption": "(A) Masson's trichrome staining of the heart of CLIP-170 S311A overexpressing mice and the control mice from 3 months and 1 year after tamoxifen treatment.",
    "ncbi_link": "CLIP-170: 56430"
  },
  {
    "caption": "(C) Representative immunostained images with an α-tubulin antibody of CLIP-170 S311A overexpressing mice heart and control mice heart over 1 year after tamoxifen treatment. (D) Quantitative analysis of intensity of α-tubulin in (C). Number of mice, (Control: n=7, S311A: n=8). Average of 5 sections per animal were analyzed. **, P<0.01 versus Control. ",
    "ncbi_link": "CLIP-170: 56430"
  },
  {
    "caption": "(G) Representative immunostained images of CLIP-170 S311A overexpressing mice heart and the control mice heart over 1 year after tamoxifen treatment. These were stained with WGA (red) and a plakoglobin antibody (green).",
    "ncbi_link": "CLIP-170: 56430"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and BMI Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression , plasma alanine aminotransferase (ALAT) (B) Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and liver fat content (C). Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "ASK1 mRNA expression in patients with different NASH scores Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG5 (E) mRNA expression. Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "ncbi_link": "ATG5: 9474
ASK1: 4217"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG7 Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D).",
    "ncbi_link": "ATG7: 10533
ASK1: 4217"
  },
  {
    "caption": "Scatter plot and correlation coefficient (r) of ASK1 mRNA expression and ATG12 mRNA expression. Data were collected in lean subjects (n=14), obese subjects (n=23) and obese subjects with type 2 diabetes (n=19). Values are expressed as mean ± SEM (D). ***",
    "ncbi_link": "ATG12: 9140
ASK1: 4217"
  },
  {
    "caption": "Shown is one representative Western blot from two independent experiments of hepatocytes transfected with siRNA targeting ASK1 (siASK1) or non-targeting siRNA control (siCtrl).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Lipid accumulation was quantified using automated image-based analysis in ASK1 knockdown (siASK1; grey bars) or control (siCtrl; black bars) cells treated with BSA, Palm, Palm+Rap and stained as mentioned above (n=4 biological replicates).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Shown is one representative Western blot from two independent experiments and quantification of LC3-II/I and p62 protein levels in siCtrl (n=4 biological replicates) or siASK1 (n=4 biological replicates) cells treated with Palm.",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Colocalization of LC3-II punctate (red; arrow) with lipid (BODIPY 493/503, green) and nuclei (Hoechst, blue) in siCtrl or siASK1 cells treated with BSA, Palm or Palm+Rap. Scale bar represents 100 µm.",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Colocalization of LC3-II punctate with lipid droplets (BODIPY 493/503, green) was quantified in hepatocytes transfected with siRNA targeting ASK1 (siASK1; grey bars) or non-targeting siRNA control (siCtrl; black bars) and treated with BSA or BSA+Baf for 24 hours (n=4 biological replicates).",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Lipid accumulation was quantified using automated image-based analysis in ASK1 knockdown (siASK1; grey bars) or control (siCtrl; black bars) cells treated with BSA, Palm or Palm+Baf and stained as mentioned above (n=4 biological replicates). Values are expressed as mean ± SEM. *",
    "ncbi_link": "ASK1: 4217"
  },
  {
    "caption": "Liver triglyceride (TG) content of mice fed a chow (ASK1F/F n=6 mice; ASK1Δhep n=6 mice) or HFD (ASK1F/F n=14 mice; ASK1Δhep n=15 mice).",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Relative mRNA expression of perilipin (Plin) and very low-density lipoprotein receptor (Vldlr) in liver of mice fed a HFD for 20 weeks (ASK1F/F n=6 mice; ASK1Δhep n=7 mice (Vldlr) or n=8 mice (Plin)).",
    "ncbi_link": "ASK1: 26408
perilipin: 103968
Plin: 103968
very low-density lipoprotein receptor: 22359
Vldlr: 22359"
  },
  {
    "caption": "Relative mRNA expression of genes involved in inflammation in liver of mice fed a HFD for 20 weeks (ASK1F/F n=6 mice; ASK1Δhep n=7 mice (F4/80, Mcp1) or ASK1Δhep n=8 mice (Il-6)).",
    "ncbi_link": "F4/80: 13733
Mcp1: 20296
Il-6: 16193
ASK1: 26408"
  },
  {
    "caption": "Relative mRNA expression of collagen, type I, alpha 1 (Col1a1) (ASK1F/F n=11 mice; ASK1Δhep n=15 mice) and transforming growth factor beta 1 (Tgfβ1) (ASK1F/F n=6 mice; ASK1Δhep n=8 mice) in liver of HFD-fed mice.",
    "ncbi_link": "Col1a1: 12842
collagen, type I, alpha 1: 12842
ASK1: 26408
Tgfβ1: 21803
transforming growth factor beta 1: 21803"
  },
  {
    "caption": "quantification of Sirius Red positive area in liver of mice fed a HFD (ASK1F/F n=8 mice; ASK1Δhep n=8 mice).",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Shown is one representative Western blot from two independent experiments and quantification of hepatic COL1A1 protein levels in mice fed a HFD for 20 weeks (ASK1F/F n=8 mice; ASK1Δhep n=8 mice).",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Liver triglyceride (TG) content (ASK1F/F n=7 mice; ASK1Δhep n=7 mice) and quantification of Sirius Red positive area in livers (ASK1F/F n=7 mice; ASK1Δhep n=7 mice) of 15 months old chow-fed mice. Values are expressed as mean ± SEM. #",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Shown is one representative Western blots from two independent experiments and quantification of respective protein levels in mice fed a HFD for 20 weeks (ASK1F/F n=8 mice; ASK1Δhep n=8 mice).",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Primary hepatocytes isolated from chow-fed ASK1F/F () and ASK1Δhep () mice were treated with BSA, Palm, Palm+Rap or Palm+Rap+Baf for 24 h. Cells were stained for lipid droplet accumulation (Bodipy 493/503, green) and nuclei (Hoechst, blue). Lipid accumulation was quantified using automated image-based analysis (n=4 biological replicates).",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Liver triglyceride (TG) content (ASK1F/F n=11 mice; ASK1+hep n=10 mice) in livers of mice fed a HFD for 20 weeks.",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Quantification of Sirius Red positive area (ASK1F/F n=11 mice; ASK1+hep n=9 mice) in livers of CCl4-injected mice.",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Relative mRNA expression (ASK1F/F n=13 mice; ASK1+hep n=14 mice) of respective genes involved in inflammation and fibrosis in liver of CCl4-injected mice. Values are expressed as mean ± SEM. #",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "Relative mRNA expression (ASK1F/F n=13 mice; ASK1+hep n=14 mice) of respective genes involved in inflammation and fibrosis in liver of CCl4-injected mice. Values are expressed as mean ± SEM.",
    "ncbi_link": "ASK1: 26408"
  },
  {
    "caption": "C. Imaging of  SPBs  (Cnm67-RFP) and Spc72-GFP  or  Mpc70-GFP in control and PHSL1-CDC20 cells. Top, time-lapse series. Bottom, meiotic events were quantified in cells synchronized  in silico  to SPB separation at entry into metaphase I  (t = 0). Graphs show overlays of SPC72-GFP and MPC70-GFP strains. Data information: data are representative of four independent experiments.",
    "ncbi_link": "CDC20: 852762
HSL1: 853760"
  },
  {
    "caption": "D. Imaging of SPBs (Cnm67-RFP) and Spc72-GFP or  Mpc70-GFP in PHSL1-CDC20  strains containing the indicated mutations. Meiotic events were analyzed as in (C). Data information: data are representative of two independent experiments.",
    "ncbi_link": "CDC20: 852762
HSL1: 853760"
  },
  {
    "caption": "A. Imaging of  SPBs (Cnm67-RFP) and Spc72-GFP or Mpc70-GFP in PHSL1-CDC20 ama1∆ control cells and spo13  mutants. Top, time-lapse series. Bottom, meiotic  events were quantified in cells synchronized  in silico to SPB  separation at entry into metaphase I (t = 0). Graphs show overlays of SPC72-GFP and MPC70-GFP strains. Data information: data are representative of two independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
HSL1: 853760
spo13: 856405"
  },
  {
    "caption": "C. Imaging of SPBs (Cnm67-RFP) and Spc72-GFP  or Mpc70-GFP in PHSL1-CDC20 ama1∆ control cells and cells containing clb1∆ or cdc28-as1, which have been treated with 1NM-PP1 at metaphase I (8 h in SPM). Meiotic events (bottom) were analyzed as in (A). Data information: data are representative of two independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
clb1: 853002
HSL1: 853760"
  },
  {
    "caption": "A. Imaging of  SPBs  (Cnm67-RFP) and Mpc70-GFP in PHSL1-CDC20 ama1∆ cells containing SPC72, spc72-7, or spc72-7 plus     hrr25-as. Cells were shifted from 24 to 36°C at 4 h in  SPM and treated with 1NM-PP1 to inhibit  Hrr25-as. Top, time-lapse series. Bottom,  Mpc70 loading to SPBs was quantified in cells synchronized  in silico to SPB  separation at entry into  metaphase I  (t = 0). Data information: data are representative of three independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
hrr25: 855897
HSL1: 853760
SPC72: 851250
spc72: 851250"
  },
  {
    "caption": "C. Imaging of  SPBs (Cnm67-RFP) and Mpc70-GFP in PHSL1-CDC20 ama1∆  spo13∆ control cells and cells expressing an additional copy of SPC72 from the PEST promoter at 4 h in SPM. Mpc70  loading (bottom) was analyzed as in (A). PEST-SPC72 expression delays the  time of Mpc70 loading by 98 min (95%  CI, 67-129; P < 0.0001; Welch's t-test). Data information: data are representative of three independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
HSL1: 853760
SPC72: 851250
spo13: 856405"
  },
  {
    "caption": "(B) Analysis of cells containing wild-type   Spo13, Spo13-mD, or Spo13-mD-m2.  Meiotic events  were quantified in cells synchronized  in silico to SPB reduplication at entry into metaphase II  (t = 0). Graphs show overlays of SPC72-GFP and  MPC70-GFP strains.  spo13-mD delays Spc72 removal and Mpc70  loading by 30 min (95%  CI, 26-34; P < 0.0001) and 60 min (95% CI, 55-66; P < 0.0001; Welch's t-test), respectively. (C) Analysis of cells expressing Clb1-mDK and different versions of  Spo13. Meiotic events were quantified as in (B). spo13-mD plus PEST-clb1-mDK delays Spc72 removal and  Mpc70  loading by 72 min (95% CI, 63-80; P < 0.0001) and 114 min (95%  CI, 99-129; P < 0.0001; Welch's t-test), respectively.",
    "ncbi_link": "Clb1: 853002
clb1: 853002
spo13: 856405
Spo13: 856405"
  },
  {
    "caption": "D.  Cdc5's polo-box domain (PBD)  binds to Ime2. Ha3-tagged versions of the wild-type PBD or the phosphopeptide-binding mutant PBD-FAA were expressed at t = 5.5 h in SPM in cells depleted of Cdc20  and Cdc5. PBD-ha3  and Ime2 were detected by immunoblotting in whole-cell extracts and α-Ha immunoprecipitates. Data information: data are representative of two independent experiments.",
    "ncbi_link": "Cdc20: 852762
Cdc5: 855013"
  },
  {
    "caption": "E.  Cdc5-dependent modification of Ime2. PHSL1-CDC20 ama1∆ control cells and cells containing  spo13∆ or  cdc5-as were treated with CMK (to inhibit Cdc5-as) at t = 8 h in SPM (arrow heads). The panel shows  immunoblot analysis of whole-cell extracts. C, sample from proliferating cells. Increased gel mobility of Ndt80 at t ≥ 10 h confirms inhibition of Cdc5-as. The arrow marks the modified form of  Ime2. Data information: data are representative of two independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
cdc5: 855013
Cdc5: 855013
HSL1: 853760
spo13: 856405"
  },
  {
    "caption": "A, B. Mitotic cdc20-3 cells were shifted to 36°C for 80 min. At t = 0, cells were treated with  estradiol  to induce expression from the PEST promoter. Top, time-lapse series from the imaging of SPBs (Cnm67-RFP) and Spc72-GFP. Frame width, 19 μm. Bottom, quantification of cells with  Spc72-GFP at SPBs. (A) Expression  of  Ime2-∆C induces removal of Spc72 from SPBs, which is inhibited by co-expression of Spo13. (B) Expression of Cdc5  plus Ime2-∆C causes rapid removal of Spc72, which is inhibited by co-expression of Spo13. Data information: data are representative of three independent experiments.",
    "ncbi_link": "cdc20: 852762
Cdc5: 855013
Ime2: 853338
Spo13: 856405"
  },
  {
    "caption": "C. Mitotic cdc20-3 cells containing PEST-CDC5 plus PEST-IME2-∆C and/or PEST-NDT80 were shifted to 36°C for 30 min and subsequently treated with  estradiol (t = 0). Top, time-lapse  series from the imaging of SPBs  (Cnm67-RFP) and Mpc70-GFP. Frame width, 19 μm. Bottom, quantification of cells with Mpc70-GFP at SPBs. Data information: data are representative of two independent experiments.",
    "ncbi_link": "cdc20: 852762
CDC5: 855013
IME2: 853338
NDT80: 856524"
  },
  {
    "caption": "C. PHSL1-CDC20 ama1∆ cdc28-as2 control cells and cells containing  spo13∆ or  cdc5-as were treated with 1Na-PP1 at t = 3 h in  SPM to inhibit Cdc28-as2. At t = 9 h in  SPM, Cdc28-as2 was activated by washing cells with cSPM lacking 1Na-PP1 (washout). cdc5-as cells were washed with cSPM plus  CMK to activate Cdc28-as2 and inhibit  Cdc5-as. Top,  time-lapse series from the imaging of Mpc70-GFP and RFP-tubulin. The weak, nuclear signal originates from Ndt80-GFP. Bottom, quantification of  spindle  formation and Mpc70  loading to  SPBs. D. PHSL1-CDC20 ama1∆ cells containing SPC72, spc72-7, or spc72-7 plus cdc5-as were shifted from 24 to 36°C at t = 4.2 h in  SPM (to inactivate Spc72-7, arrow heads) and treated with CMK at t = 6 h in SPM (to inhibit Cdc5-as). Top, time-lapse  series from the imaging of SPBs (Cnm67-RFP) and Mpc70-GFP. Bottom, quantification of SPB separation and Mpc70 loading to  SPBs. Inhibition of  Cdc5-as in spc72-7 cells advances the  time of Mpc70  loading by 119 min (95% CI, 76-162; P < 0.0001; Welch's t-test). Data are representative of two independent experiments.",
    "ncbi_link": "ama1: 853140
CDC20: 852762
cdc28: 852457
Cdc28: 852457
cdc5: 855013
Cdc5: 855013
HSL1: 853760
SPC72: 851250
spc72: 851250
Spc72: 851250
spo13: 856405"
  },
  {
    "caption": "A. Inhibition of Cdk1 at anaphase I. CDC20-mAR and CDC20-mAR cdc28-as1 cells were released from the metaphase I-arrest with CuSO4 at 7 h in SPM  (t = 0) and treated with 1NM-PP1  at t = 40 min to inhibit Cdc28-as1 (arrows). Top, time-lapse series from the imaging of Mpc70-GFP, SPBs (Cnm67-RFP), and nuclei  (TetR-RFP). Bottom, quantification of meiotic events.",
    "ncbi_link": "CDC20: 852762
cdc28: 852457"
  },
  {
    "caption": "Western blotting of Myc-Egg expressed in OSCs. Anti-Myc (Myc) and anti-β-Tubulin (Tub) antibodies were used. Tub was detected as a loading control. Control: empty vector was used as a negative control.",
    "ncbi_link": "Myc: 
Egg: 37962"
  },
  {
    "caption": "Western blotting of Myc-Egg WT and its K1085R and S215/T217 (STAA) mutants expressed in OSCs. Egg modifications identified in this study are summarized on the right. P: phosphorylation. Ub: monoubiquitination.",
    "ncbi_link": "Myc: 
Egg: 37962"
  },
  {
    "caption": "Rescue assays. Myc-Egg WT and its K1085R and STAA mutants were expressed in OSCs upon endogenous Egg depletion (siEgg). Western blotting (WB) was performed using anti-Egg and anti-Myc antibodies. RT-qPCR was used to quantify Stalker2 transposon expression level. The act5c gene was used for normalization. siEGFP: siRNA for EGFP was used as a negative control. Error bars represent SD from three independent experiments. *p < 0.05 (unpaired Student's t-test). n.s.: not significant.",
    "ncbi_link": "act5c: 
EGFP: 
Myc: 
Stalker2: 
Egg: 37962"
  },
  {
    "caption": "Western blotting of Myc-Egg expressed in OSCs before (siEGFP) and after (siUbc2) Ubc2 depletion. Anti-Myc-antibody was used for western blotting. The ratios of mUb-Egg over non-mUb-Egg band signals were 1.43 (siEGFP) and 0.78 (siUbc2).",
    "ncbi_link": "EGFP: 
Ubc2: 34487"
  },
  {
    "caption": "Immunofluorescence analysis of Myc-Egg WT, Myc-SV40-NLS-Egg, and Myc-PKI-NES-Egg expressed in OSCs using anti-Myc antibody. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Myc: 
Egg: 37962"
  },
  {
    "caption": "Western blotting of Myc-Egg WT, Myc-SV40-NLS-Egg, and Myc-PKI-NES-Egg expressed in OSCs. Anti-Myc antibody was used. The ratios of mUb-Egg over non-mUb-Egg band signals were 1.50 (WT), 2.29 (SV40-NLS), and 0.95 (PKI-NES).",
    "ncbi_link": "Myc: 
Egg: 37962"
  },
  {
    "caption": "Rescue assays. Myc-Egg WT, Myc-SV40-NLS-Egg, and Myc-PKI-NES-Egg were expressed in OSCs upon endogenous Egg depletion (siEgg). Western blotting was performed using anti-Egg (left) and anti-Myc (right) antibodies. Stalker2 transposon expression was quantified using RT-qPCR. The act5c gene was used for normalization. siEGFP: siRNA for EGFP was used as a negative control. Error bars represent SD from three independent experiments. *p < 0.05 (unpaired Student's t-test).",
    "ncbi_link": "act5c: 
Stalker2: 
EGFP: 
Myc: 
Egg: 37962"
  },
  {
    "caption": "Rescue assays. Myc-Egg WT, Myc-Egg K1085R, and Myc-SV40-NLS-K1085R were expressed in OSCs upon endogenous Egg depletion (siEgg). Western blotting was performed using anti-Egg (left) and anti-Myc (right) antibodies. RT-qPCR quantified the expression level of the Stalker2 transposon. The act5c gene was used for normalization. siEGFP: siRNA for EGFP was used as a negative control. Error bars represent SD from three independent experiments. *p < 0.05 (unpaired Student's t-test).",
    "ncbi_link": "act5c: 
Stalker2: 
EGFP: 
Myc: 
Egg: 37962"
  },
  {
    "caption": "Immunofluorescence analysis of endogenous Egg (red) in OSCs using anti-Egg antibody before (siEGFP) and after (siWde) Wde depletion. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "EGFP: 
Wde: 36133"
  },
  {
    "caption": "Western blotting on fractionated materials of OSCs before (siEGFP) and after (siWde) Wde depletion. Anti-Egg, anti-Wde, anti-Tub, and anti-H3 antibodies were used. H3 and Tub were detected as markers for nuclear (Nuc) and cytoplasmic (Cyto) fractions, respectively. Whole: whole OSC lysates.",
    "ncbi_link": "EGFP: 
Wde: 36133"
  },
  {
    "caption": "Immunofluorescence analysis of endogenous Egg (red) in OSCs upon Flag-Wde (green) co-expression. Anti-Egg and anti-Flag antibodies were used. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
Wde: 36133"
  },
  {
    "caption": "Immunofluorescence analysis of Myc-Egg WT (red) in OSCs upon Wde co-expression (green). Anti-Myc and anti-Flag antibodies were used. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Wde: 36133"
  },
  {
    "caption": "Western blotting on fractionated materials of Myc-Egg-expressed OSCs before (-) and after Wde WT and Wde ∆CC co-expression. Anti-Myc, anti-Flag, anti-Tub, and anti-H3 antibodies were used. H3 and Tub were detected as markers for nuclear (Nuc) and cytoplasmic (Cyto) fractions, respectively. Whole: the whole OSC lysates.",
    "ncbi_link": "Myc: 
Egg: 37962
Wde: 36133"
  },
  {
    "caption": "Protein-protein interaction assays. Myc-Egg and Flag-Wde WT and its ∆CC mutant were expressed in OSCs. Immunoprecipitation was conducted using anti-Flag antibody while anti-Myc (upper) and anti-Flag (lower) antibodies were used for western blotting.",
    "ncbi_link": "Flag: 
Myc: 
Egg: 37962
Wde: 36133"
  },
  {
    "caption": "Immunofluorescence analysis of Myc-Egg WT (red) in OSCs upon Flag-Wde WT and ∆CC mutant (green) co-expression. Anti-Myc and anti-Flag antibodies were used. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
Wde: 36133"
  },
  {
    "caption": "Immunofluorescence analysis of Myc-Egg WT, Myc-Egg K987A, and Myc-Egg R988A mutants (red) in OSCs before and after Flag-Wde (green) co-expression. Anti-Myc and anti-Flag antibodies were used. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
Wde: 36133"
  },
  {
    "caption": "Western blotting of Myc-Egg WT and its K987A and R988A mutants. Flag-Wde: Flag-Wde was co-expressed. SV40-NLS: SV40-NLS was added to Myc-Egg. Anti-Myc and anti-Flag antibodies were used.",
    "ncbi_link": "Flag: 
Myc: 
Egg: 37962
Wde: 36133"
  },
  {
    "caption": "Protein-protein interaction assays. Myc-Egg WT, Myc-SV40-NLS-Egg WT, and Myc-SV40-NLS-Egg K1085R mutant were expressed with Flag-Wde in OSCs. Immunoprecipitation was conducted using anti-Flag antibody while anti-Myc (upper) and anti-Flag (lower) antibodies were used for western blotting.",
    "ncbi_link": "Flag: 
Myc: 
Egg: 37962
Wde: 36133"
  },
  {
    "caption": "Rescue assays. Myc-Egg WT and Myc-SV40-NLS-Egg WT were expressed in OSCs upon endogenous Egg and Wde depletion (siEgg and siWde). Western blotting was performed using anti-Egg (left) and anti-Myc (right) antibodies. RT-qPCR quantified the expression level of Stalker2 transposon. The act5c gene was used for normalization. siEGFP: siRNA for EGFP was used as a negative control. Error bars represent SD from three independent experiments. *p < 0.05 (unpaired Student's t-test).",
    "ncbi_link": "act5c: 
Stalker2: 
EGFP: 
Myc: 
Egg: 37962
Wde: 36133"
  },
  {
    "caption": "Western blotting of Myc-SV40-NLS-Egg WT in whole (Whole), cytoplasm/nucleoplasmic (Cyto/Np) and chromatin (Chromatin) fractions before (-) and after Flag-Wde co-expression. Anti-Myc and anti-Flag antibodies were used. Histone H3 was detected as a marker of chromatin fraction.",
    "ncbi_link": "Flag: 
Wde: 36133"
  },
  {
    "caption": "Immunofluorescence analysis of H3K9me3 (green), Myc-Egg WT (red), and Myc-SV40-NLS-Egg WT (red) in OSCs before and after Flag-Wde (yellow) co-expression. Anti-H3K9me3, anti-Myc and anti-Flag antibodies were used. DAPI (blue) shows the nuclei. Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
Wde: 36133"
  },
  {
    "caption": "Heatmaps of Egg ChIP-seq signal within 10 kb windows centered on Egg peaks in control (siEGFP) and Wde-depleted (siWde) OSCs.",
    "ncbi_link": "EGFP: 
Wde: 36133"
  },
  {
    "caption": "ChIP-qPCR was performed before (siEGFP) and after (siWde) Wde depletion. qPCR was performed for Piwi target transposons (Stalker2, mdg1, and gypsy) and normalized to %input of a PIwi non-target transposon (roo). Error bars represent SD from three independent experiments.",
    "ncbi_link": "Stalker2: 
EGFP: 
gypsy: 
mdg1: 
roo: 
Wde: 36133"
  },
  {
    "caption": "Density plots for Egg ChIP-seq signal on Stalker2, mdg1, and gypsy in control (siEGFP) and Wde-depleted (siWde) OSCs. Input: input DNA was used as a control. RPM: reads per million mapped reads.",
    "ncbi_link": "gypsy: 
EGFP: 
mdg1: 
Stalker2: 
Wde: 36133"
  },
  {
    "caption": " Mice were infected with sub-lethal dose (25 pfu) of influenza virus and assessed as follows (B) Relative amount of PR8 viral NP mRNA, by qPCR Data information: Data are representative of three independent experiments with 3-5 mice per group and represented as mean ± S.E.M ",
    "ncbi_link": "NP: 956531"
  },
  {
    "caption": "Mice were superinfected as described in Fig 3A. (A) Bacterial load as determined by enumeration of cfu in BAL following administration of αIL-17 or αIL-22 blocking antibody. Control wild-type and T-bet-/- groups were administered with IgG isotype control antibody Data information Dat are combined from two independent experiments (n = 8-12 mice per group) All data are represented as mean ± S.E.M. Statistical significance was determined with Kruskal-Wallis test followed by Dunn\"s multiple comparisons test n.s. = not significant",
    "ncbi_link": "T-bet: 57765"
  },
  {
    "caption": "Mice were superinfected as described in Fig 3A (B) T-bet-/- mice were administered αIL-17 or IgG isotype control antibody every other day from day -2 post-secondary bacterial infection and monitored for survival Data information: Dat are combined from two independent experiments (n = 8-12 mice per group) All data are represented as mean ± S.E.M. Statistical significance was determined wit logrank test in (B",
    "ncbi_link": "T-bet: 57765"
  },
  {
    "caption": "Mice were superinfected as described in Fig 3A (D) Pneumococcal cfu in BAL following αLy6G antibody mediated neutrophil depletion. Control T-bet-/- mice were administered with IgG isotype control antibody Data information: Dat are combined from two independent experiments (n = 8-12 mice per group) All data are represented as mean ± S.E.M. Statistical significance was determined wit Mann-Whitney U test in (D",
    "ncbi_link": "T-bet: 57765"
  },
  {
    "caption": "The RNA-seq data of CTH was downloaded from the TCGA database (H) The mRNA expression of CTH in PC specimens and normal tissues. Data are presented as means ± SD (n=50 cases for adjancent non-tumor parts and 469 cases for PC tumors). Student's t-test was used for the statistical analysis (**P<0.01).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(I) Kaplan-Meier survival analysis of PC patients with high or low CTH expression. The statistical significance was determined using the χ2 test.",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(A) Western blot analysis of the CTH level in PC3-T2 cells with CTH overexpression by pCMV-CTH-HA or PC3-B2 cells with CTH knockdown by siCTH-1.",
    "ncbi_link": "HA: 
CTH: 1491"
  },
  {
    "caption": "(B) Top: The H2S production capacity of cell lysates from PC3-T2 cells with CTH overexpression by pCMV-CTH-HA or PC3-B2 cells with CTH knockdown by siCTH-1. Lead acetate-soaked paper strips show a PbS brown stain as a result of reaction with H2S. Bottom: The level of H2S production was quantified by densitometry, and the histograms represent the means ± SD (n=3 biological replicates). ANOVA followed by Tukey's post-hoc test was used for the statistical analysis (*P<0.05).",
    "ncbi_link": "HA: 
CTH: 1491"
  },
  {
    "caption": "(C) PC3-B2 cells were transfected with control or siCTH-1 and then were subjected to migration (16h) and invasion (24h) assays. Data information: Data shown represent the means ± SD (n=3 biological replicates). Student's t-test was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(D) Cell proliferation rates of PC3-B2 cells with CTH knockdown. Cell proliferation assay was performed by MTS reagent. Data information: Data shown represent the means ± SD (n=3 biological replicates). Student's t-test was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(E) Western blot analysis of the CTH levels in PC3 cells transfected with HA-CTH or pCMV-HA vector control.",
    "ncbi_link": "HA: 
CTH: 1491"
  },
  {
    "caption": "(F) PC3 cells were transfected with HA-CTH or pCMV-HA vector control and then incubated for migration (16h) and invasion assay (24h). Data information: Data shown represent the means ± SD (n=3 biological replicates). Student's t-test was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "HA: 
CTH: 1491"
  },
  {
    "caption": "(A) Real-Time RT-PCR analysis for IL-1β mRNA levels in PC3 cells with control or CTH knockdown. Recombinant IL-1β (10ng/ml) was added for 24h in serum-free medium. Data information: All data shown represent the means ± SD (n=3 biological replicates). ANOVA followed by Tukey's post-hoc test was used for the statistical analysis. (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491
IL-1β: 3553"
  },
  {
    "caption": "(B) ELISA assay for IL-1β protein level in the culture medium of PC3 cells with control or CTH knockdown. Data information All data shown represent the means ± SD (n=3 biological replicates). Student's t-test (B) was used for the statistical analysis. (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(C) PC3 cells transfected with control or CTH knockdown were incubated for invasion (24h) assay with recombinant IL-1β (10ng/ml) added to the medium of the lower chamber. Data information: All data shown represent the means ± SD (n=3 biological replicates). ANOVA followed by Tukey's post-hoc test was used for the statistical analysis. (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(D) PC3 cells transfected with control or CTH siRNA were exposed to IL-1β (20ng/ml) for 1hr. Subcellular localization of p65 was detected by immunocytochemistry. Nuclei were counterstained with DAPI. The representative images are shown. Scale bars: 25μm.",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "Real-Time RT-PCR analysis for VEGF (F) mRNA level in PC3 cells with control or CTH knockdown. Recombinant IL-1β (10ng/ml) was added for 24h in serum-free medium. Data information: All data shown represent the means ± SD (n=3 biological replicates). ANOVA followed by Tukey's post-hoc test was used for the statistical analysis. (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491
VEGF: 7422///7423"
  },
  {
    "caption": "Real-Time RT-PCR analysis for MMP-13 (G) mRNA level in PC3 cells with control or CTH knockdown. Recombinant IL-1β (10ng/ml) was added for 24h in serum-free medium. Data information: All data shown represent the means ± SD (n=3 biological replicates). ANOVA followed by Tukey's post-hoc test was used for the statistical analysis. (*P<0.05; **P<0.01; ***P<0.001).",
    "ncbi_link": "CTH: 1491
MMP-13: 4322"
  },
  {
    "caption": " (B) PC3 cells transfected with control or CTH siRNA were incubated for invasion (24h) assay. DMEM/10% FBS, with or without NaHS (1μM), acting as a chemoattractant Data information Data shown represent the means ± SD (n=3 biological replicates) ANOVA followed by Tukey's post-hoc tes was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001)",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": " (E) Real-Time RT-PCR analysis for IL-1β, VEGF, and MMP-13 mRNA levels in PC3 cells treated with 1μM NaHS for 24h Data information Data shown represent the means ± SD (n=3 biological replicates) Student's t-tes was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001)",
    "ncbi_link": "IL-1β: 3553
MMP-13: 4322
VEGF: 7423///7422"
  },
  {
    "caption": " (G) Western blot analysis of the p65 expression in PC3 cells with p65 knock-out and then transfected with p65 wild-type or C38S mutant Data information Data shown represent the means ± SD (n=3 biological replicates)",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": " (H) PC3 cells with p65 knock-out with or without overexpression of p65 wild-type or C38S mutant were incubated for invasion assay for 24 hrs. DMEM/10% FBS was used as a chemoattractant Data information Data shown represent the means ± SD (n=3 biological replicates) ANOVA followed by Tukey's post-hoc tes was used for the statistical analysis (*P<0.05; **P<0.01; ***P<0.001)",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "1x106 PC3 cells with p65 knock-out were transiently re-expressed p65 wild-type or C38S mutant and inoculated into the bloodstream via tail-vein injection. After 7 days of inoculation, mouse lung was collected to examine lung metastasis. (I) Images show H&E staining of the lungs from mice injected with p65 knockout PC3 cells re-expressing p65 wild-type or C38S mutant. Red arrows indicate metastatic nodules. Scale bar: 1mm",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "1x106 PC3 cells with p65 knock-out were transiently re-expressed p65 wild-type or C38S mutant and inoculated into the bloodstream via tail-vein injection. After 7 days of inoculation, mouse lung was collected to examine lung metastasis The total metastatic nodules per lung (J were quantified. Data are presented as means ± SEM (n=7 mice per group). Student's t-test was used for the statistical analysis (*P<0.05)",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "1x106 PC3 cells with p65 knock-out were transiently re-expressed p65 wild-type or C38S mutant and inoculated into the bloodstream via tail-vein injection. After 7 days of inoculation, mouse lung was collected to examine lung metastasis percentage of the metastatic area per lung (K) were quantified. Data are presented as means ± SEM (n=7 mice per group). Student's t-test was used for the statistical analysis (*P<0.05)",
    "ncbi_link": "p65: 5970"
  },
  {
    "caption": "(A) Western blot analysis of the CTH expression in PC3 cells stably expressing control or CTH shRNA.",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "1x106 PC3 cells with control or CTH knockdown were orthotopically injected into the mouse prostate for 60 days. The tumor weight (B), and tumor volume (C) were compared. Data are presented as means ± SEM (n = 10 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "1x106 PC3 cells with control or CTH knockdown were orthotopically injected into the mouse prostate for 60 days. Incidences of paraaortic lymph nodes metastasis (D) and bone metastasis (E) are shown. Data are presented as means ± SEM (n = 10 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(F) Real-Time RT-PCR analysis for CTH mRNA levels in PC3 orthotopic tumors from shCon or shCTH group. Data shown represent normalized means ± SEM (n=10 mice per group). Data information: Student's t-test was used for the statistical analysis (*P<0.05).",
    "ncbi_link": "CTH: 1491"
  },
  {
    "caption": "(C) TFR1 mRNA levels in  muscle biopsies from cancer-patients of late stage  cachexia (19 healthy subjects, 17  cachectic patients with at least 10% total body weight loss) Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "TFR1: 7037"
  },
  {
    "caption": "(F) TFR1  mRNA levels in the gastrocnemius of  mice subjected to  iron deprivation by feeding with an  iron deficient diet (IDD) combined to a phlebotomy  (PHL) (n=5-6) Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "TFR1: 22042"
  },
  {
    "caption": "(G) Cross-sectional area of skeletal muscle fiber  transfected with shSCR (scramble) and shTFR1 (n=3-4) and representative picture of a shTFR1 transfected  fiber. Scale bar=50µm. (H) Cross-sectional area of skeletal muscle fibers  transfected with TFR-pHuji  (n=4) and representative picture of a  TFR-pHuji  transfected  fiber. Scale bar=50µm. Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "pHuji: 
TFR: 7037
TFR1: 7037"
  },
  {
    "caption": "(C-D) mRNA levels of mitochondrial iron  importer  MFRN2 (C) and the rate limiting enzyme of heme synthesis ALAS2 (D) normalized to  18s in mouse gastrocnemius (n=4-5). Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "18s: 
ALAS2: 11656
MFRN2: 246696"
  },
  {
    "caption": "(I-K) mRNA levels of Murf 1  (I), Atrogin 1 (J), and REDD1  (K) normalized to GAPDH in  gastrocnemius  (n=5-14). Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by one-way Anova with Bonferroni's correction, Data are mean ± SEM. ∗p < 0.05 and ∗∗∗p < 0.001 compared to control and #p < 0.05, ##p < 0.01, ###p < 0.001 compared to  C26  untreated group.",
    "ncbi_link": "REDD1: 74747
Atrogin 1: 67731
GAPDH: 14433
Murf 1: 433766"
  },
  {
    "caption": "(F-H) mRNA levels of  ACOT 1 (F),  MCD (G), and CPT1B (H) normalized to GAPDH in gastrocnemius (n=5-10). Data information: For all data, n represents the number of biological replicates. Statistical significance was calculated by unpaired, two-tailed Student's T-test. Data are mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 compared to control and #p < 0.05, ##p < 0.01, ###p < 0.001 compared to C26 untreated group.",
    "ncbi_link": "ACOT 1: 26897
CPT1B: 12895
GAPDH: 14433
MCD: 56690"
  },
  {
    "caption": "(A) Brigthfield images of human patient derived organoids (PDOs) from gastric cancer with and without RTK/MAPK alterations (scale bar 100µm, zoom in 40µm).",
    "ncbi_link": "RTK: 780///4914
MAPK: 5602///5601///5599///5598///5597///5596///5595///5594"
  },
  {
    "caption": "(B) Drug response curves of PDOs upon treatment with the MEK1/2 inhibitor trametinib (biological replicates n=3, data are presented as mean, SD values are shown in Table EV2). (C) Drug response curves upon HDAC inhibition with panobinostat (PAN) and entinostat (ENT) (biological replicates n=3, data are presented as mean, SD values are shown in Table EV2). (D) Comparison of the relative area under the curve (AUCrel) upon trametinib treatment in RTK/MAPK altered (mean AUCrel: 0.5308; biological replicate n=7) vs. non‑altered (mean AUCrel: 0.7101; biological replicates n=6) human PDOs (two‑tailed Student's t‑Test; *p= 0.0356).",
    "ncbi_link": "RTK: 780///4914
MAPK: 5602///5601///5599///5598///5595///5594///5597///5596"
  },
  {
    "caption": "A. Structure of Brca1ex2 allele. * Note that exon 4 was annotated in error in original descriptions of the gene structure and is not drawn. RT-PCR shows a novel product from the Brca1ex2 allele, corresponding to splicing of exon 1 directly to exon 3.",
    "ncbi_link": "Brca1: 12189"
  },
  {
    "caption": "B. Western blot to detect BRCA1 and BARD1 in MEFs expressing WT and mutant Brca1.",
    "ncbi_link": "Brca1: 12189"
  },
  {
    "caption": "C. Immunofluorescent (IF) detection of BRCA1 and RAD51 at IR-induced nuclear foci in cells expressing WT and mutant forms of Brca1. Scale bar: 10 ingD. Quantification of IF, showing proportion of cells with RAD51 foci that also had >5 BRCA1 foci. N=2.E. Quantification of IF, showing proportion of RAD51 foci that colocalized with BRCA1 foci. N=2.",
    "ncbi_link": "Brca1: 12189"
  },
  {
    "caption": "F. Immunofluorescent detection of BARD1 at IR-induced nuclear foci in MEFs expressing WT and mutant forms of Brca1. Scale bar: 10 μ S",
    "ncbi_link": "Brca1: 12189"
  },
  {
    "caption": "A. Western blot showing abundance of BRCA1 and BARD1 protein in Brca1Δ2/Δ2;Trp53bp1-/- mouseB cells.",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "B. Analysis of chromosome aberrations in mice with targeted deletion of Brca1 exon 2 and Trp53bp1. Left, metaphase spreads were prepared from B cells treated with olaparib. Arrows show examples of chromosome aberrations. Right, quantification of chromosome breaks (CSB), chromatid-type breaks (CTD), radial chromosomes, and other abnormalities in mouseB cells. Error bars indicate SD, N=3",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "A. Kaplan-Meier survival curve for Brca1ex2/+;Trp53bp1-/- and Brca1ex2/ex2;Trp53bp1-/- mice. N=20 animals in each group. Statistical analysis by Mantel-Cox log-rank test.",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "B. Kaplan-Meier survival curve for Brca1ex2/+;Trp53bp1-/-;Trp53+/- and Brca1ex2/ex2;Trp53bp1-/-;Trp53+/- mice. N=20 animals in each group. Statistical analysis by Mantel-Cox log-rank test.",
    "ncbi_link": "Brca1: 12189
Trp53: 22059
Trp53bp1: 27223"
  },
  {
    "caption": "C. Percentage of Brca1ex2/+;Trp53bp1-/- and Brca1ex2/ex2;Trp53bp1-/- mice showing signs of abnormal tissue morphology at death. N=46 animals inspected for Brca1ex2/+;Trp53bp1+/+, N=54 animals inspected for Brca1ex2/ex2/Trp53bp1-/-.",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "D. Tissues affected by abnormal growth from N=46 Brca1ex2/+/Trp53bp1-/- and N=54 Brca1ex2/ex2/Trp53bp1-/- mice.",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "A. H&E-stained sections of seminiferous tubules from testes of WT and Brca1ex2/ex2/Trp53bp1-/- male mice. Scale bar: 100 μm.",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "B. Immunofluorescence on meiotic chromosomes from WT and Brca1ex2/ex2;Trp53bp1-/-spermatocytes. Spreads were stained for SYCP3 to indicate chromosome axes and extent of synapsis and were stained for SYCP3 to indicate chromosome axex body. Scale bar: 5 apsi",
    "ncbi_link": "Brca1: 12189
Trp53bp1: 27223"
  },
  {
    "caption": "(G) LMP1 binds  directly to ANT1 dependent on its transmembrane domain in 293T  cells.  IP/IB was used to detect the interaction between Flag-tagged   LMP1  mutants and Myc-tagged  ANT1. IP  of cell lysates using a  Flag or Myc antibody.",
    "ncbi_link": "Flag: 
Myc: 
LMP1: 3783750
ANT1: 291"
  },
  {
    "caption": "(E) Wild-type (WT) and Ews-/- embryos mid-brain at E17.5 days were subjected to TUNEL assay. Scale bar indicates 100 μm (lnsert).",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(A) Western blot analysis of Parp1 and DNA damage markers in Wild-type (WT) and Ews-/- mBA cells. Cells were treated with MMS (0.02%) in a time dependent manner. Proteins were fractionated into two groups, chromatin-bound (Chro) proteins and soluble (Solu) proteins. (B) After treatment with MMS (0.02%, 1hour), the media was replaced to release the DNA damage. The proteins were fractionated and the specific protein kinetics at chromatin was analyzed by western blot.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(C) GFP-PARP1 U2OS cells were transfected with siControl and siEWS. Local DNA damage was induced by micro-irradiation using a 405nm laser. Data represented as mean ±SEMs and more than six cells were analyzed from six independent experiments. The statistical significance determined by One-way ANOVA, ***P< 0.001. Scale bar indicates 5 μm.",
    "ncbi_link": "EWS: 2130"
  },
  {
    "caption": "(D) Fluorescence correlation spectroscopy (FCS) was measured after 15 minutes later following micro-irradiation (Upper) or under normal condition in GFP-PARP1 U2OS cells with either siControl or siEWS. Data represented as mean ±SEMs, more than 50 cells were analyzed, and significance determined by One-way ANOVA, ***P< 0.001. Scale bar indicate 5 μm.",
    "ncbi_link": "EWS: 2130"
  },
  {
    "caption": "(E) AsiSI endonuclease-integrated U2OS cells were transfected with siControl and siEWS. Cells were incubated with doxycycline for 4 hours to induce DSBs. With or without changing the Dox-added media to fresh media for 2 hours (for release samples), the amount of chromatin-associated PARP1 was measured using ChIP assay. (N.T: Non-treat, T: AsiSI treat, Release: Damage released samples). Data represented as mean ±SEMs, and technical repeats (n=3), significance determined by two-way ANOVA, ***P< 0.001.",
    "ncbi_link": "AsiSI: 
EWS: 2130"
  },
  {
    "caption": "(A) Total levels of PAR in whole cell lysate were measured using western blot analysis. Wild-type (WT) and Ews-/- mBA cells were treated with H2O2, (1 mM, 20 minutes) with or without Olaparib (5 μM, 7 hours).",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(B) The kinetics of PAR accumulation was analyzed by western blotting. WT and Ews-/- cells were treated with H2O2 (1 mM, 20 minutes), followed by incubation in fresh media for the indicated times to allow release of DNA damage",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(C) Immunohistochemistry detection of PAR by ADP-ribose antibody in WT and Ews-/- cells after H2O2 treatment (1 mM, 20 minutes) and recovery from DNA damage. Right graph displays mean of intensities measured from 500 cells. Data represented as mean ±SEMs, significance determined by One-way ANOVA, ***P < 0.001. Scale bar indicate 20 μm.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(D, E) Whole cell level of PAR was measured in WT and Ews-/- mBA cells upon treatment with (D) MMS (0.02%, 60 minutes) (E) with or without recovery from DNA damage.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(E) Schematic map of nine EWS mutants (left) and IP-western blot analysis (right). GFP-PARP1 and siPARG were transfected into HEK-293 cells with each EWS mutants plasmid. After H2O2 treatment, the cells were conducted to IP with anti-Flag antibody.",
    "ncbi_link": "EWS: 2130
PARG: 8505
PARP1: 142"
  },
  {
    "caption": "(F) Western blot analysis of PARP1 accumulation on chromatin. EWS-WT and M4 mutants were transfected into EWS depleted HEK-293 cells. After treatment of MMS (0.02%, 1 hour), the proteins were fractionated to either chromatin-bound or soluble fraction. (G) Quantification of relative amount of PARP1 and γH2AX on chromatin, divided by chromatin H3, from three independent western experiments are presented. Data represented as mean ±SEMs, were measured from 3 independent experiments. Significance determined by t-test. * P < 0.05, **P < 0.01. n.s indicate non-significance",
    "ncbi_link": "EWS: 2130"
  },
  {
    "caption": "(H) WT and Ews-/- cells were transfected with EWS-WT and -M4 mutant and cell viability was measured 24 hours after MMS treatment (indicated concentration). Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, **P < 0.01. n.s indicate non-significance,",
    "ncbi_link": "Ews: 2130
EWS: 2130"
  },
  {
    "caption": "(A) Relative cell viability of cells transfected with siCon (WT), siEWS (EWS KD), PARP1 (PARP-1 KD), and double siRNA (DKD) after MMS treatment. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, ***P < 0.001. Analysis (***) indicates differences between DKD with EWS KD.",
    "ncbi_link": "EWS: 2130
PARP-1: 142
PARP1: 142"
  },
  {
    "caption": "(B) Additional Parp1 knockout in Ews knockout cells (DKO) were subjected to viability test after MMS treatment. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, ***P < 0.001. *** indicated differences between DKO with EWS-KO.",
    "ncbi_link": "Ews: 14030
EWS: 14030
Parp1: 11545"
  },
  {
    "caption": " C) After transfection of siCon, siEWS, PARP1, and double siRNA, the effect of co-depletion of PARP1 and EWS on the γH2AX and phosphorylated CHK1 upon MMS treatment was analyzed by western blot. ",
    "ncbi_link": "EWS: 2130
PARP1: 142"
  },
  {
    "caption": "D) After treatment of MMS, the effect of additional Parp1 knockout in Ews knockout cells (Double KO) to the γH2AX and phosphorylated CHK1 were analyzed using western blot.",
    "ncbi_link": "Ews: 14030
Parp1: 11545"
  },
  {
    "caption": "E) Whole cell expression of PAR in mBA (WT: Ews-WT, KO: Ews-KO, DKO: double KO).",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "F) Relative NAD+/NADH ratios were measured in WT, Ews-/- and DKO cells. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, ***P < 0.001.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "G) PARGi (5 μM, 24 hours) treated WT and Ews-/- cells were subjected to cellular viability assay. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "H) Relative cellular viability was measured after NMN treatment, with or without MMS pretreatment, in WT and Ews-/- cells. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, ***P < 0.001.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "I) Chromatin-bound PARP1 was quantified by western blot in WT and Ews-/- cells treated with Olaparib (5 μM, 24 hours) treatment.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "J) Relative viability was measured in WT and Ews-/- cells upon treatment of Olaparib for 24 hours. Error bars represent as mean ±SEMs, and technical repeats (n=3). Significance determined by Two-way ANOVA, ***P < 0.001.",
    "ncbi_link": "Ews: 14030"
  },
  {
    "caption": "(a-d) Formation of protein inclusions in SY5Y cells expressing FL (a) or the indicated truncated forms of Sph1 (b-d) was induced by 12 h lactacystin treatment. After extensive washes, cells were maintained in serum-supplemented (serum+) or serum-free (serum−) media, and in the absence (Control) or presence of 10 mM 3-MA, an inhibitor of macroautophagy. Graphs show the relative fold difference in the number of cells containing either Sph1 Agm (left) or Agg (right) observed under different recovery conditions. Values are mean+s.e. (n=4). *Significant versus serum+ condition. See also Supplementary Figs S1-S5.",
    "ncbi_link": "Sph1: 9627"
  },
  {
    "caption": "(a-c) Top: fluorescence images of Agm and Agg observed in MEFs from WT and Atg5 KO mice expressing FL (a), or the indicated truncated Sph1 proteins (b-c) treated with lactacystin (12 h) and recovered in basal conditions (serum+). Graphs show the relative fold difference in the number of cells containing either Sph1 Agm (middle) or Agg (bottom). Values are mean+s.e. (n=3). *Significant versus control.",
    "ncbi_link": "Atg5: 11793
Sph1: 67847"
  },
  {
    "caption": "(d-f) Relative fold difference in the number of FL (d) or truncated (e-f) Sph1 Agm (left) and Agg (right) in WT and Atg5 KO mice MEFs incubated in serum+ or serum− conditions. Values are mean+s.e. (n=3). *Significant versus serum+ condition.",
    "ncbi_link": "Atg5: 11793
Sph1: 67847"
  },
  {
    "caption": "(a-d) Left: fluorescence images of SY5Y cells co-expressing HA-p38 (red) and GFP (green) forms of FL (a) or the indicated truncated Sph1 (b-d). Cells were treated with lactacystin (12 h) and recovered in the presence or absence of serum. Graphs: percentage of p38 existing alone in Agm or co-aggregating with Sph1 in the forms of Agm or Agg (left), and susceptibility of p38 existing on its own in Agm or co-aggregating with Sph1 proteins in Agm toward serum-stimulated autophagic clearance (right). Values are expressed as folds Agm in the presence of serum and are mean+s.e. (n=3). *Significant versus serum+ condition calculated using Student's t-test.",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "(e) Autophagic susceptibility of Agm formed by p38 and ANK1-p38 fusion proteins. Values are mean+s.e. (n=3). *Significant versus control group calculated using Bonferroni test. See also Supplementary Fig. S6.",
    "ncbi_link": "p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(a) Top: colocalization of LAMP1 (red) with Agm and Agg of ACA and CACT Sph1 proteins highlighted by anti-GFP (green) in SY5Y cells. Arrows indicate colocalization. Bottom: percentage LAMP1 colocalization with Agm and Agg in cells maintained in serum+ or serum− media, treated or not with lysosomal inhibitors (N/L).",
    "ncbi_link": "Sph1: 9627"
  },
  {
    "caption": "(b) Percentage LAMP1 colocalization with Agm in cells co-expressing HA-p38 and the indicated Sph1 proteins maintained in the absence of serum.",
    "ncbi_link": "p38: 1432///5600///5603///6300
Sph1: 9627"
  },
  {
    "caption": "(c) Left: colocalization of LAMP1 (red) with GFP-p38 and -ANK1-p38 Agm in SY5Y cells maintained in the absence of serum. Arrows indicate colocalization. Right: percentage LAMP1 colocalization with p38 and ANK1-p38 Agm in cells maintained in the presence or absence of serum.",
    "ncbi_link": "p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(d,e) Correlative light and electron microscopy of SY5Y cells expressing the indicated GFP-tagged Sph1 truncations (d), or p38 and ANK1-p38 (e). Top: phase-contrast fluorescence microscopy; middle: electron micrographs of the boxed region; bottom: higher magnification examples of autophagic vacuoles (yellow arrows). #Location of the Agm or Agg structures in both the fluorescence images and the corresponding micrographs.",
    "ncbi_link": "p38: 5603///5600///6300///1432
Sph1: 9627"
  },
  {
    "caption": "(f) Top: colocalization of LC3 (red) with GFP-p38 and -ANK1-p38 Agm in SY5Y cells maintained in the absence of serum. Arrows indicate colocalization. Bottom: percentage colocalization of LC3 with the fluorescent proteins. Values in all graphs represent mean+s.e. (n=3). *Significant versus serum+ condition (a,c,f) or p38 Agm (b) calculated using Bonferroni test. See also Supplementary Fig. S7.",
    "ncbi_link": "p38: 1432///5603///5600///6300
p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(a) Fluorescence images showing colocalization patterns of the indicated GFP-p38 variants and Sph1 (green) with endogenous p62 (red) in SY5Y cells. Arrows indicate colocalization.",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "(b) Quantitative FRAP analysis of mCherry-p62 expressed alone (control) or co-expressed with the indicated GFP-Sph1 and -p38 variants. Top: time course of changes in relative fluorescence intensity (RFI); bottom: percentage of p62 in the diffusing fraction and diffusion time (t1/2). Values are mean+s.e. of ten cells analysed over three different experiments. Representative images are shown in Supplementary Fig. S8.",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "(c-d) Top: IBs for p62 and actin in control and p62 knockdown (p62 KD #325 or #788) SY5Y cells (c); and in control and p62 KO MEFs (d). Bottom: autophagic clearance of GFP-ANK1-p38 Agm in the same cells in response to serum removal.",
    "ncbi_link": "p38: 1432///5603///6300///5600
p62: 18412
p62: 8878"
  },
  {
    "caption": "(e) Fluorescence images of GFP-p38, -ANK1-p38 and -NA Sph1 Agm in SY5Y cells immunostained for endogenous NBR1. Arrows indicate colocalization.",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "(f,g) Top: IBs for NBR1, p62 and actin in control and NBR1 knockdown (NBR1 KD #161) SY5Y cells (f), and in control and p62/NBR1 double knockdown (Double KD #A or #B) SY5Y cells (g). Bottom: autophagic clearance of GFP-ANK1-p38 Agm in the same cells. For all densitometric analyses, values are mean+s.e. (n=3). *Significant versus serum+ condition. See also Supplementary Fig. S8-S11.",
    "ncbi_link": "p38: 1432///5603///6300///5600
NBR1: 4077
p62: 8878"
  },
  {
    "caption": "(a-d) Fluorescence images of GFP-p38, -ANK1-p38 and -NA Sph1 Agm in SY5Y cells immunostained for endogenous beclin-1 (a), Vps34 (b), Atg14L (c) and DFCP-1 (d). Arrows indicate colocalization.",
    "ncbi_link": "p38: 5600///6300///5603///1432
Sph1: 9627"
  },
  {
    "caption": "(a) Quantitative FRAP analysis of the indicated GFP-p38 variants. Top: representative images. Middle: time course of changes in relative fluorescence intensity (RFI). Bottom: percentage of proteins in the diffusing fraction and diffusion time (t1/2). Values are mean+s.e. of ten cells analysed over three different experiments. Scale bars, 10 μm",
    "ncbi_link": "p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(b) Top: schematic showing all lysine (K) residues in ANK1 domain of Sph1 that may serve as potential ubiquitination site(s). Bottom: relative fold difference in the number of Agm formed by WT and the different 'K to R' mutants of ANK1-p38 fusion protein in SY5Y cells maintained in the presence or absence of serum.",
    "ncbi_link": "p38: 1432///5603///5600///6300
Sph1: 9627"
  },
  {
    "caption": "(c) IBs for HA (top) and GFP (bottom) of total lysates (Input) and GFP immunoprecipitates (IP) from the cell lysates of SY5Y cells co-transfected with the indicated HA-ubiquitin constructs and GFP-p38 or -ANK1-p38 WT or mutant K385R in the presence of lactacystin. (d) Quantification of the levels of each p38 protein ubiquitinated via K63 compared with K48 ubiquitination. Values were corrected by levels of GFP immunoprecipitated.",
    "ncbi_link": "p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(e) Top: IF for GFP and K63-linked ubiquitin (red) of SY5Y cells expressing GFP-p38 or -ANK1-p38 WT and mutant K385R (green). Arrows indicate colocalization. Bottom: percentage of Agm positive for K63-linked ubiquitin.",
    "ncbi_link": "p38: 1432///5603///6300///5600"
  },
  {
    "caption": "(f) Quantitative FRAP analysis of GFP-ANK1-p38 K385R and GFP-ANK1-p38 as in (a). Values are mean+s.e. of ten cells analysed over three different experiments.",
    "ncbi_link": "p38: 1432///5603///5600///6300"
  },
  {
    "caption": "(g) Top: representative images of GFP-ANK1-p38 K385R Agm in SY5Y cells immunostained for Atg14L, Vps34 and DFCP-1. Bottom: percentage of p38 variant and NA Sph1 Agm that colocalized with Atg14L, Vps34 and DFCP-1 under serum− conditions. Values in all graphs represent mean+s.e. (n=3). *Significant versus serum+ condition or p38 Agm. #Significant versus ANK1-p38 Agm. Significance calculated using Bonferroni test. See also Supplementary Fig. S8.",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "(a,b) Autophagic clearance of Agm (a) or Agg (b) formed by FL WT and mutant K385R or K394R GFP-Sph1 in SY5Y cells, in response to serum removal (a) or upon blockage of basal autophagy with 3-MA (b).",
    "ncbi_link": "Sph1: 9627"
  },
  {
    "caption": "(c,d) Left: Agm (c) or Agg (d) of FL GFP-Sph1 (green) immunostained for endogenous K63-linked ubiquitin (red) in SY5Y cells. Arrows in (c) indicate colocalization. Right: percentage of Agm (c) or Agg (d) positive for K63-linked ubiquitin.",
    "ncbi_link": "Sph1: 9627"
  },
  {
    "caption": "(e) Formation of WT and mutant K385R FL Sph1 (left) and ANK1-p38 (right) Agm in response to proteasome inhibition. Values in all graphs represent mean+s.e. (n=3). *Significant versus serum+ condition (a,b) or WT FL Sph1 or ANK1-p38 (c-e).",
    "ncbi_link": "p38: 1432///5603///6300///5600
Sph1: 9627"
  },
  {
    "caption": "Northern blotting shows that Gasz depletion (Gasz KD) led to the accumulation of flam-piRNA precursors but reduced the level of mature idefix-piRNA arising from the precursors, as in the case of Zuc depletion (Zuc KD). U6 snRNA was detected as a loading control.",
    "ncbi_link": "idefix: 
U6: 
Gasz: 35795
flam: 26067356
Zuc: 34609"
  },
  {
    "caption": "Left: Western blotting comparing the abundances of Armi and Piwi in total OSC lysate (total) and the mitochondrial fraction (mito) before (control) and after (Zuc KD) Zuc knockdown in OSCs. Relative mito-localization intensity (*) shows the amount of proteins in "mito" normalized by the amount of proteins in "total" and HSP60. Right: Immunofluorescence shows that the Armi signal (green) is strongly overlapped with the mitochondrial signal (red) in Zuc-depleted OSCs (Zuc KD). Armi is localized to Yb bodies in control OSCs (control). The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Zuc: 34609"
  },
  {
    "caption": "Left: Western blotting comparing the abundances of Armi and Piwi in total OSC lysate (total) and the mitochondrial fraction (mito) before (control) and after (Gasz KD) Gasz depletion in Zuc-depleted OSCs (Zuc KD). Relative mito-localization intensity (*) shows the amount of proteins in "mito" normalized by the amount of proteins in "total" and HSP60. Right: Immunofluorescence shows that the Armi mitochondrial signal (green) found in Zuc-depleted cells (Zuc KD/control) mostly disappeared after additional Gasz depletion in the cells (Zuc KD/Gasz KD), but was found at Yb bodies. Mitochondrial signal is shown in red. The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Gasz: 35795
Zuc: 34609"
  },
  {
    "caption": "Armi and Piwi co-immunoprecipitated with Flag-Gasz (F-Gasz) from the mitochondrial fraction (mito fraction) of OSCs (input). F-Gasz was ectopically expressed in the cells by transfection prior to immunoprecipitation. *: Heavy chains of antibodies used for immunoprecipitation. n.i.: Non-immune IgG used as a negative control.",
    "ncbi_link": "Gasz: 35795"
  },
  {
    "caption": "Co-immunoprecipitation from whole-cell lysate of OSCs before (control) and after (Zuc KD) Zuc depletion and subsequent western blotting show that the levels of Piwi and Armi in the Flag-Gasz (F-Gasz) complex increased upon Zuc depletion (Zuc KD).",
    "ncbi_link": "Flag: 
Gasz: 35795
Zuc: 34609"
  },
  {
    "caption": "Northern blotting shows that the flam-piRNA precursors in the Flag-Gasz complex (Flag) accumulated upon Zuc depletion (Zuc KD).",
    "ncbi_link": "Flag: 
Gasz: 35795
flam: 26067356
Zuc: 34609"
  },
  {
    "caption": "Upper: The flam-piRNA precursors associated with Piwi disappeared upon Armi depletion (Armi KD) in Zuc-lacking OSCs (Zuc KD). Lower: The abundance of immunopurified Piwi is shown by western blotting.",
    "ncbi_link": "Armi: 38427
flam: 26067356
Zuc: 34609"
  },
  {
    "caption": "Depletion of endogenous Piwi (Piwi KD) in Zuc-lacking OSCs (Zuc KD) caused Armi (green) to relocate to Yb bodies. Localization of Armi at Yb bodies is shown in B. Mitochondrial (upper panel) and Yb (lower panel) signals are shown in red. The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "The Armi complex was immunopurified from Zuc-lacking OSCs (Zuc KD) before (control) and after (Piwi KD) Piwi depletion and probed for detecting Armi and Gasz. Armi no longer stably associated with endogenous Gasz upon Piwi depletion in Zuc-lacking OSCs. Co-IP index (*) shows that the ratio of Gasz amount in the Armi complex isolated from Zuc-depleted cells (Zuc KD/control) and Zuc- and Piwi-depleted cells (Zuc KD/Piwi KD) is 1:0.05.",
    "ncbi_link": "Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "The Flag-Gasz (F-Gasz) complex was immunopurified from Zuc-lacking OSCs (Zuc KD) before (control) and after (Piwi KD) Piwi depletion and probed for detecting Armi and F-Gasz. F-Gasz was ectopically expressed prior to immunoprecipitation. Co-IP index (*) shows that the ratio of Armi amount in the F-Gasz complex isolated from Zuc-depleted cells (Zuc KD/control) and Zuc- and Piwi-depleted cells (Zuc KD/Piwi KD) is 1:0.31.",
    "ncbi_link": "Gasz: 35795
Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "Upper: Northern blotting shows that Flag-Piwi WT (WT) and PAZ mutant (PAZmt) but not MID mutant (MIDmt) bound with flam-piRNA precursors in Zuc-depleted OSCs. Endogenous Piwi was depleted simultaneously with Zuc (Zuc KD + Piwi KD). Zuc was depleted by RNAi and so residual Zuc may have remained in cells. Therefore, a tiny amount of piRNAs was loaded onto Piwi. F-Piwi WT, PAZmt, and MIDmt were made to be RNAi-resistant by mutagenesis (see Materials and Methods). Lower: The abundance of immunopurified Flag-Piwi (F-Piwi) is shown by western blotting.",
    "ncbi_link": "Flag: 
flam: 26067356
Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "Armi localization to Yb bodies observed in Zuc- and Piwi-depleted OSCs (Zuc KD + Piwi KD) (Figs 3A and B) was restored by ectopic expression of Flag-Piwi WT and PAZmt but not of MIDmt (see also Fig EV4B). Armi, mitochondria, and F-Piwi are shown in green, red, and yellow, respectively. The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Flag: 
Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "Western blotting shows that Flag-Piwi (F-Piwi) WT (WT) and PAZ mutant (PAZmt) but not MID mutant (MIDmt) bound with Armi in Zuc/Piwi-depleted OSCs (Zuc KD + Piwi KD).",
    "ncbi_link": "Flag: 
Piwi: 34521
Zuc: 34609"
  },
  {
    "caption": "Armi-Flag (Armi-F) WT and the N756A mutant were expressed in OSCs where endogenous Armi and Zuc had been depleted by RNAi (Zuc KD + Armi KD). Immunoprecipitation and subsequent western blotting show that Armi-F WT bound with Piwi and Gasz. The Armi N756A mutant bound with Piwi strongly but only weakly with Gasz. Luciferase-Flag (Luc-F) was used as a negative control.",
    "ncbi_link": "Flag: 
Armi: 38427
Zuc: 34609"
  },
  {
    "caption": "Armi-Flag (Armi-F) WT and the N756A mutant were expressed in OSCs where endogenous Armi and Zuc had been depleted by RNAi (Zuc KD + Armi KD). Armi-F WT (green) localized onto mitochondria (red), whereas Armi-F N756A mutant (green) localized to Yb bodies (see also Fig EV5D). The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Flag: 
Armi: 38427
Zuc: 34609"
  },
  {
    "caption": "Armi-Flag (Armi-F) WT and the ∆N34 mutant were expressed in OSCs where endogenous Armi and Zuc had been depleted by RNAi (Zuc KD + Armi KD). Immunoprecipitation and subsequent western blotting show that Armi-F WT but not Armi ∆N34 mutant bound with Gasz in the cells. Both Armi WT and ∆N34 mutant interacted with Piwi to similar extents. Luciferase-Flag (Luc-F) was used as a negative control.",
    "ncbi_link": "Flag: 
Luciferase: 
Armi: 38427
Zuc: 34609"
  },
  {
    "caption": "Armi-Flag (Armi-F) WT and the ∆N34 mutant were expressed in OSCs where endogenous Armi and Zuc had been depleted by RNAi (Zuc KD + Armi KD). Armi-F WT (green) localized onto mitochondria (red), whereas Armi-F ∆N34 mutant (green) localized to Yb bodies (see also Fig EV6D). The scale bar represents 5 μm. DAPI (blue) shows the nuclei.",
    "ncbi_link": "Flag: 
Armi: 38427
Zuc: 34609"
  },
  {
    "caption": "Immunoprecipitation and subsequent western blotting shows that Armi-Flag (Armi-F) but not Flag-Armi (F-Armi) strongly bound with Gasz in Zuc/Armi-depleted OSCs (Zuc KD + Armi KD). Piwi bound with both Armi (F-Armi and Armi-F). Luciferase-Flag (Luc-F) was used as a negative control.",
    "ncbi_link": "Flag: 
Luciferase: 
Armi: 38427
Zuc: 34609"
  },
  {
    "caption": "D. Quantitative PCR analysis of SHARPIN mRNA expression in cell populations isolated in (C) (mean ± SEM, n = 3 - 5).",
    "ncbi_link": "SHARPIN: 106025"
  },
  {
    "caption": "A-G. Mammary ductal outgrowth in 3-7 weeks old wt or Sharpincpdm female mice. A. Representative carmine-alum stained mammary gland whole mounts. Arrow indicates the inguinal lymph node. Scale bars represent 2 mm. B. Quantification of mammary ductal outgrowth area (n = 4 - 15 glands). C. Quantification of the number of ductal branch points per mammary gland (n = 7 - 9 glands, 7 weeks old mice).",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A-G. Mammary ductal outgrowth in 3-7 weeks old wt or Sharpincpdm female mice. D. Cryosections from 7 weeks old wt or Sharpincpdm mouse mammary glands stained with HE (upper panel) or immunolabelled with the indicated antibodies. Scale bars represent 20 μm",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A-G. Mammary ductal outgrowth in 3-7 weeks old wt or Sharpincpdm female mice. E. Representative carmine-alum stained images highlighting terminal end buds (TEBs) in 7 weeks old wt and Sharpincpdm mouse mammary glands and F. quantification of the number of TEBs per gland (n = 9 - 10 glands). Scale bar represents 500 μm.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A-G. Mammary ductal outgrowth in 3-7 weeks old wt or Sharpincpdm female mice. G. TEBs in paraffin sections from wt or Sharpincpdm mouse mammary glands stained with HE (upper panel) or immunolabelled with the indicated antibodies (lower panel). Scale bars represent 50 µm. Mean ± SEM.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A-C. Monitoring of mammary gland development following transplantation of wt or Sharpincpdm mouse mammary epithelium in the mammary fat pads (epithelium-free) of virgin wt mice. A. Representative carmine-alum stained images of mouse mammary glands generated from wt or Sharpincpdm epithelial tissue transplants. B. Quantification of transplant growth take-on-rate (n = 17). C. Quantification of fat pad filling rate of grown transplants (n = 7 - 10) in wt hosts.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "D. Monitoring of mammary gland differentiation during pregnancy following transplantation of wt or Sharpincpdm mouse mammary epithelium into wt hosts. Host animals were subsequently mated and mammary glands isolated at P15. Representative Carmine-alum stained mammary gland whole mounts generated from wt and cdpm mammary epithelial transplants (upper panel), and magnifications of the branched ductal epithelium (lower panel) are shown (n = 5 mice). Scale bars represent 1 mm.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "E. Representative images of carmine-alum stained mouse mammary gland whole mounts generated from 7 weeks old S100a4-Cre; Sharpinfl/fl conditional knockout mice and their littermate controls (S100a4-Cre; Sharpin fl/+) F. Quantification of the normalized Sharpincpdm and S100a4-Cre; Sharpinfl/fl mammary ductal outgrowth area relative to littermate control mice (wt and Sharpincpdm n = 10 glands; S100a4-Cre; Sharpin fl/+ and S100a4-Cre; Sharpinfl/fl n = 8 glands). G. Quantification of the number of TEBs per gland (n = 8 - 9 glands). Mean ± SEM.",
    "ncbi_link": "Cre: 
S100a4: 20198
Sharpin: 106025"
  },
  {
    "caption": "A. Second harmonic generation (SHG) and unfiltered multiphoton (MP) imaging of collagen fibres surrounding TEBs (dashed line) in 6-7 weeks old wt and Sharpincpdm mouse mammary glands (n = 6 - 9 mice, 5 - 13 TEBs analysed per mouse; scale bars represent 100 µm). Magnified images of collagen fibres are also shown (scale bars represent 50 µm). B. Frequency of clear collagen bundles around TEBs per mouse (Mean ± SEM, n = 6 - 9 mice).",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "C. AFM indentation analysis of stromal stiffness in 6-7 weeks old wt and Sharpincpdm mouse mammary gland tissue sections (n = 3 mice; 3 - 6 sample sections per mouse and 192 indentation curves per sample).",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A. Ingenuity Pathway Analysis of differential gene expression (fold-change (FC) > 1.5, p < 0.05) in wt and Sharpincpdm MSFs (passage 0). The differentially expressed genes implicated in the most significantly altered canonical pathways (leukocyte adhesion and transmigration, and tissue fibrosis) are shown. Three independent cell isolation replicates were compared pairwise. FC colour scale represents a range from 0−4.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "C-D. Collagen plug contraction assay using wt and Sharpincpdm MSFs or wt MSFs with SHARPIN siRNA silencing C. Representative light microscopy images of the collagen plugs three days post cell culture. D. Quantification of the average collagen plug area 1−3 days after seeding (n = 3-6). Scale bars represent 2 mm.",
    "ncbi_link": "SHARPIN: 106025
Sharpin: 106025"
  },
  {
    "caption": "E. SHARPIN protein level after silencing with negative control siRNA or SHARPIN siRNA in wt MSFs. Tubulin was used as loading control.",
    "ncbi_link": "SHARPIN: 106025"
  },
  {
    "caption": "F-I. Traction force microscopy analysis of wt and Sharpincpdm MSFs on collagen-coated matrices. F. Representative images of traction forces observed in wt and Sharpincpdm cells (colour scale units: Pa; cell boundaries are indicated by dashed lines). G. Quantification of strain energy per cell (n = 8 − 11 cells from two independent experiments).",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "F-I. Traction force microscopy analysis of wt and Sharpincpdm MSFs on collagen-coated matrices. H. Representative images of the traction forces and mCherry fluorescence of mCherry-Ctrl transfected wt cells and mCherry-Ctrl or mCherry-SHARPIN transfected Sharpincpdm cells. Scale bars represent 20 µm. I. Quantification of strain energy per cell (wt mCherry control n = 26; Sharpincpdm mCherry-Ctrl n = 21; Sharpincpdm mCherry-SHARPIN n = 24 cells from five independent experiments).",
    "ncbi_link": "Sharpin: 106025
SHARPIN: 106025"
  },
  {
    "caption": "J-K. Focal adhesion dynamics. J. Visualization of GFP-Paxillin dynamics in a wt and a Sharpincpdm cell over time. Colour scale represents a range from early to late occurring focal adhesions. K. Quantification of focal adhesion average size, assembly rate and disassembly rate (wt n =17527, 5250, 5311 FAs; and Sharpincpdm n= 9052, 2790, 3264 FAs, respectively from two independent experiments). Mean ± SEM.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "A. Quantification of soluble collagen levels in wt and Sharpincpdm MSF cultures on days 2, 5 and 7 post serum removal (n = 6 from two independent experiments).",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "B-C. Analysis of the collagen network in cell-derived matrices (CDMs) produced by wt and Sharpincpdm MSFs using COL1A1 immunolabelling. B. Maximum intensity projections of confocal images are shown. Scale bars represent 50 μm. C. Quantification of distinct collagen fibre bundles in wt and Sharpincpdm CDM samples (n = 5). Mean ± SEM.",
    "ncbi_link": "Sharpin: 106025"
  },
  {
    "caption": "Representative confocal images of cell-type-specific promoter::GFP:AGO1 translational fusions.",
    "ncbi_link": "AGO1: 
GFP: "
  },
  {
    "caption": "Left: input and IPed AGO1 following post-lysis addition of a radiolabeled siRNA duplex (siGFP). Right: northern analysis of AGO1-bound sRNAs.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Representative confocal images of cell-type-specific promoter::GFP transcriptional fusions in hyl1 vs WT roots.",
    "ncbi_link": "hyl1: 837498"
  },
  {
    "caption": "Hierarchical clustering of validated miRNA targets between different cell layers in either WT or hyl1 roots.",
    "ncbi_link": "hyl1: 837498"
  },
  {
    "caption": "qRT-PCR validation of three distinct classes of direct miRNA target transcripts from total root-, total root polysome- or epidermis-specific polysome-associated RNA. The AT2G37050 kinase is positively regulated by LAC17. Scale bars: 50μM. All qPCR values were normalized to the internal control ACTIN2.",
    "ncbi_link": "ACTIN2: 
AT2G37050 kinase: 818281
LAC17: 836124"
  },
  {
    "caption": "miRoot snapshots of whole-root (left) and layer-specific (right) LAC17 mRNA accumulation in WT versus hyl1, as assessed by polysome profiling.",
    "ncbi_link": "hyl1: 837498
LAC17: 836124"
  },
  {
    "caption": "miRoot snapshot of cell-type specific miRNAs showing, in this case, a sum group of the miR156 family. The right panel shows the gradient of expression revealed upon removal of the stele (blue box).",
    "ncbi_link": "miR156: 28718130///28716731///5008308///5007886///28721198///3770614///28721147///28720200///28720191///28718303"
  },
  {
    "caption": "Snapshot of the SPL6 miR156 translatome in WT and hyl1 backgrounds. Removal of the stele (blue box) reveals subtleties of miR156-mediated gene regulation in the other layers, resulting in a near-mirror image of (A).",
    "ncbi_link": "SPL6: 843248
hyl1: 837498
miR156: 28718130///28716731///5008308///5007886///28721198///3770614///28721147///28720200///28720191///28718303"
  },
  {
    "caption": "Confocal image of pmiR396a::H2B:GFP. Normalized read counts from AGO1-IP-Seq and independent northern analysis of AGO1-loaded miR396.",
    "ncbi_link": "GFP: 
H2B: 
miR396: 5007870
miR396a: 5007870"
  },
  {
    "caption": "Representative confocal image of the pGRF2::H2B:GFP translational fusion.",
    "ncbi_link": "GFP: 
H2B: 
GRF2: 844165"
  },
  {
    "caption": "Focused miRoot analysis of the GRF2 translatome signal in WT versus hyl1 columella. Graph: GRF2 normalized read counts.",
    "ncbi_link": "GRF2: 844165
hyl1: 837498"
  },
  {
    "caption": "Representative confocal images of the pGRF2::GRF2:GFP translational fusion in WT or hyl1 backgrounds.",
    "ncbi_link": "GFP: 
GRF2: 844165
hyl1: 837498"
  },
  {
    "caption": "Focused miRoot analysis of the PLT1 translatome signal in WT versus hyl1 columella.",
    "ncbi_link": "hyl1: 837498
PLT1: 821632"
  },
  {
    "caption": "Layer-specific normalized read counts of miR169 paralogs (separated into 4 different groups based on sequence identity: a, b-c, d-g, h-n) from AGO1-IP-deep-Seq and independent northern analysis, as in Fig.1F.",
    "ncbi_link": "miR169: 5008036///5008035///5008034///5008033///5008032///5008031///5007706///5008152///5008003///5007800///5007801///5008285///5008226///28719269"
  },
  {
    "caption": "Cell-type specific AGO1-IP signals for each miR169 sequence-group with (upper) or without (lower panel) the miRoot scale normalization option.",
    "ncbi_link": "miR169: 5008033///5008032///5008031///5008152///5008003///5008285///5008036///5008035///5008034///5007706///5007800///5007801///5008226///28719269"
  },
  {
    "caption": "Predicted base-pairing of indicated miR169 sequence-group to four NF-YA target transcripts. Pairing with expectation value greater than 3 was not considered. The color gradient (pale: low, dark: strong) qualitatively approximates the pairing contribution of each miR169 sequence-group according to the upper panel of (B). miRoot snapshots of layer-specific translatome signals of four out-of-seven miR169 NF-YA targets in WT versus hyl1 backgrounds.",
    "ncbi_link": "hyl1: 837498
miR169: 5007800///5008035///5008033///5008003///5008226///5007706///5008034///5008036///5008032///5008031///5008152///5007801///5008285///28719269
NF-YA: 821640///841856///843614///819738"
  },
  {
    "caption": "Browser representation and independent northern analysis and AGO1-loaded miR165/166.",
    "ncbi_link": "miR165: 3766638
166: 3771553///3771422///3771398///3770612///3770611///3769765///28718357"
  },
  {
    "caption": "miRoot snapshot of PHB translatome signals in WT versus hyl1 backgrounds.",
    "ncbi_link": "hyl1: 837498
PHB: 818036"
  },
  {
    "caption": "Representative confocal images of pmiR395(a/c/e)::H2B:GFP transcriptional fusions under SO4--deficient or SO4--proficient growth conditions. Northern analysis of AGO1-loaded miR395 under the conditions in (C).",
    "ncbi_link": "GFP: 
H2B: 
miR395: 5007844///5007729///5007727"
  },
  {
    "caption": "Representative confocal images of the pAPS4::APS4:GFP translational fusion under the conditions in (C).",
    "ncbi_link": "GFP: 
APS4: 834400"
  },
  {
    "caption": "Representative confocal image of the pSHR::GFP:P19 translational fusion and (B) principle of P19-based miRNA duplex sequestration.",
    "ncbi_link": "GFP: 
P19: 
SHR: 829919"
  },
  {
    "caption": "Binding of miR395 by SHR::HA:P19 under SO4--sufficient (+) and -deficient (-) growth conditions.",
    "ncbi_link": "HA: 
P19: 
miR395: 5007727///5007729///5007844
SHR: 829919"
  },
  {
    "caption": "qRT-PCR analysis of polysome-associated APS4 in the cortex or epidermis in the presence (+) or absence (-) of SHR::HA:P19. Signals are relative to SHR::HA:P19 (-) lines given a value of 1.",
    "ncbi_link": "HA: 
P19: 
APS4: 834400
SHR: 829919"
  },
  {
    "caption": "Representative confocal image of the pmiR397b::H2B:GFP transcriptional fusion (left) and the browser AGO1-loaded signal for miR397b (right).",
    "ncbi_link": "GFP: 
H2B: 
miR397b: 5008141"
  },
  {
    "caption": "miR160 northern analysis in whole-leaf, vasculature and epidermis. U6: loading control.",
    "ncbi_link": "U6: 
miR160: 3771452///3770127///3768181"
  },
  {
    "caption": "Western analysis of the promoter::H2B:GFP translational fusions shown in (5C) in the cell types isolated in (G).",
    "ncbi_link": "GFP: 
H2B: "
  },
  {
    "caption": "qRT-PCR analysis of ARF17 in whole-leaves or in separated cell types in WT versus hyl1 backgrounds.",
    "ncbi_link": "ARF17: 844120
hyl1: 837498"
  },
  {
    "caption": "A Immunoblot of PPAR-α and Tubulin (control) (top) in WAT from WT and FADD-D mice with relative quantification (bottom). Data are expressed as mean ± SEM from three independent experiments. *P = 0.0035 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B Immunostaining of PPAR-α expression in WAT from WT and FADD-D mice (Scale bars = 50 μm). Shown are typical results from four different fields and three different experiments.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Quantitative real time PCR for PPAR-α and PPAR-α target genes, using RNA from epididymalfat from 10-week-old male WT and FADD-D mice fed a SD. Data are expressed as mean ± SEM from two independent experiments (n = 6 total for each genotype). *P = 0.0022, **P = 0.0083, ***P = 0.0107, #P = 0.0011, ##P = 0.0037 (Student's t-test).",
    "ncbi_link": "FADD: 14082
PPAR-α: 19013"
  },
  {
    "caption": "D ChIP assay of CPT1b promoter in adipocytes isolated from WT, FADD-D and ad-FADDmice. Soluble chromatin from adipocytes was immunoprecipitated with control mouse IgG or antibodies against PPAR-α. The experiments were performed in triplicate.",
    "ncbi_link": "CPT1b: 12895
FADD: 14082"
  },
  {
    "caption": "E ChIP assay of CPT1b promoter in adipocytes isolated from WT and FADD-D mice. Soluble chromatin from adipocytes was immunoprecipitated with control mouse IgG or antibodies against FADD. The experiments were performed in triplicate.",
    "ncbi_link": "CPT1b: 12895
FADD: 14082"
  },
  {
    "caption": "F PPAR-α and RIP140coimmunoprecipitate in WT but not FADD knockout or FADD-D MEFs. PPAR-α was immunoprecipitated (IP) from the cell lysates of WT or FADD knockout MEFs. Data shown are representative of three independent experiments having similar results.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "G PPAR-α and RIP140coimmunoprecipitate in WT but not FADD knockout MEFs upon WY-14,643 stimulation. Ligand-dependent interactions were examined in the presence of 100 μM WY-14,643 where indicated. Data shown are representative of three independent experiments having similar results.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "H Coimmunoprecipitation analysis of FADD and RIP140 in 293T cells. As indicated, lysates from the cells transfected with plasmids encoding Flag-RIP140, HA-FADD-A or HA-FADD-D were subjected to immunoprecipitation with an anti-Flag antibody. FADD-A and FADD-D were detected using an anti-HA antibody. Data shown are representative of three independent experiments having similar results.",
    "ncbi_link": "FADD: 8772"
  },
  {
    "caption": "I Coimmunoprecipitation analysis of FADD and PPAR-α in 293T cells. As indicated, lysates from the cells transfected with plasmids encoding Flag-FADD-A, Flag-FADD-D or HA-PPAR-α were subjected to immunoprecipitation with an anti-Flag antibody. PPAR-α was visualized by anti-HA. Data shown are representative of three independent experiments having similar results.",
    "ncbi_link": "FADD: 8772"
  },
  {
    "caption": "A Left, Body weights of male WT and FADD-D mice on either a SD (n = 8 for each genotype) or a HFD (n = 6 for each genotype). Right, Food intake per mouse fed a HFD measured over 20 days normalized by body weight (n = 10 for each genotype). Results are means ± SEM. *P = 0.0007 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B Representative photographs of fat pads and organs of 10-week-old male FADD-D and WT mice.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Left, fat pad weights as a percentage of body weight (BW) and in absolute amounts (inset) from male FADD-D and WT mice. Mice were fed a SD or a HFD until 15 weeks of age (n = 6 for each genotype). Results are means ± SEM. *P = 0.0012, **P = 0.0002, ***P = 0.0027, ****P = 0.0014, ^P = 0.0038, ^^P = 0.0019, #P = 0.0045, ##P = 0.0007, *^P = 0.0252, *^^P = 0.0082, ###P = 0.0275, ####P = 0.0071 (one-way ANOVA). Middle, fat pad weights of male FADD-D and WT mice on a HFD at 30 weeks of age (n = 6 for each genotype). Inset, triacylglycerol (TAG) content in epididymal WAT. Data are expressed as means ± SEM. *P = 0.0003, **P = 0.0005, ***P = 0.0019, ****P = 0.0011 (Student's t-test). Right, weight of liver normalized by body weight for male FADD-D and WT littermates at the age of 15 weeks (n = 6 for each genotype). Data are expressed as means ± SEM. NS, not statistically significant (Student's t-test). Epi, epididymal fat; Ren, renal fat; Ing, inguinal fat.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Left, fat pad weights as a percentage of body weight (BW) and in absolute amounts (inset) from male FADD-D and WT mice. Mice were fed a SD or a HFD until 15 weeks of age (n = 6 for each genotype). Results are means ± SEM. *P = 0.0012, **P = 0.0002, ***P = 0.0027, ****P = 0.0014, ^P = 0.0038, ^^P = 0.0019, #P = 0.0045, ##P = 0.0007, *^P = 0.0252, *^^P = 0.0082, ###P = 0.0275, ####P = 0.0071 (one-way ANOVA). Middle, fat pad weights of male FADD-D and WT mice on a HFD at 30 weeks of age (n = 6 for each genotype). Inset, triacylglycerol (TAG) content in epididymal WAT. Data are expressed as means ± SEM. *P = 0.0003, **P = 0.0005, ***P = 0.0019, ****P = 0.0011 (Student's t-test). Right, weight of liver normalized by body weight for male FADD-D and WT littermates at the age of 15 weeks (n = 6 for each genotype). Data are expressed as means ± SEM. NS, not statistically significant (Student's t-test). Epi, epididymal fat; Ren, renal fat; Ing, inguinal fat.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "F Paraffin-embedded sections of WAT and BAT from WT and FADD-D mice were stained with H&E. Scale bar = 50 μm. Shown are typical results from four different fields and three different experiments.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "G Left, relative amounts of liver and muscle triacylglycerol contents in 10-month-old WT and FADD-D mice (n = 6 for each genotype). Right, relative amounts of cholesterol in the liver and muscle of the same group of WT and FADD-D mice (n = 6 for each genotype). Data are expressed as means ± SEM. *P = 0.0015, **P = 0.0027, ***P = 0.0318 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "H Left, plasma triacylglycerol levels in 10-month-old WT and FADD-D mice following fasting for 20 h (n = 5 for each genotype). Right, plasma cholesterol levels in the same group of WT and FADD-D mice (n = 5 for each genotype). Data are expressed as means ± SEM. *P = 0.0124 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A Serum free fatty acid (FFA) levels and triacylglycerol levels in WT and FADD-D mice fed a HFD for 20 days (n = 5 for each genotype). Data are expressed as means ± SEM. *P = 0.0059, **P = 0.0012 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B Serum levels of leptin in WT and FADD-D mice (n = 4 for each genotype) fed a SD or a HFD. Data are expressed as means ± SEM. *P = 0.0032, **P = 0.0003, ***P = 0.0038 (one-way ANOVA).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Morphology of inguinal WAT, BAT, and liver from WT and FADD-D mice fed a HFD for 20 days. WAT and BAT were stained with hematoxylin and eosin. Liver tissues were stained with Oil red O to demonstrate lipid accumulation and counterstained with hematoxylin. Scale bars = 50 μm. Shown are typical results from four different fields and three different experiments.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "D Comparison of cell size in WAT of WT and FADD-D mice maintained on SD and HFD (n = 5 for each genotype).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "E FADD-D mice lost more weight as compared with WT on 20-h fasting (n = 4 for each genotype). Data are expressed as means ± SEM. *P = 0.0085 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "F Whole-body oxygen consumption rate (VO2) during 24 hr in WT and FADD-D mice fed a SD (n = 4 for each genotype). Data are expressed as means ± SEM. *P = 0.0055, **P = 0.0081 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "G Average respiratory exchange ratio (VCO2/VO2) (RER) for the dark and light period in WT and FADD-D mice (n = 5 for each genotype). Data are expressed as means ± SEM. *P = 0.0042, **P = 0.0079 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "I Average values of energy expenditure (EE) for the 24 hr period in WT and FADD-D mice (n = 5 for each genotype). Data are expressed as means ± SEM. *P = 0.0054 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "J Physical activity for the dark and light period in WT and FADD-D mice (n = 5 for each genotype). Data are expressed as means ± SEM. NS, not statistically significant (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A Left, transmission electron microscopy analysis of adipocytes from WAT and BAT of WT and FADD-D mice. Arrowheads indicate mitochondria and lipid droplets (L) (× 5,000 magnification). Right, quantification of mitochondria in WAT and BAT of WT and FADD-D mice, respectively. Data are expressed as mean ± SEM from three independent experiments (n = 6 total for each genotype). *P = 0.0007, **P = 0.0083 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B Quantitative real time PCR for UCP1, Dio2, PPARd, UCP3, CPT1 and PGC1-α, using RNA from epididymalfat from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from three independent experiments (n = 6 total for each genotype). *P = 0.0014, **P = 0.0025, ***P = 0.0006, ****P = 0.0007, #P = 0.0003, ##P = 0.0008 (Student's t-test).",
    "ncbi_link": "CPT1: 12895///12894
Dio2: 13371
FADD: 14082
PPARd: 19015
PGC1-α: 19017
UCP1: 22227
UCP3: 22229"
  },
  {
    "caption": "C Quantitative real time PCR for UCP3, CPT1, PPARd and PGC1-α, using RNA from skeletal muscle from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from three independent experiments (n = 6 total for each genotype). *P = 0.0027, **P = 0.0329, ***P = 0.0092, ****P = 0.0085 (Student's t-test).",
    "ncbi_link": "CPT1: 12895///12894
FADD: 14082
PPARd: 19015
PGC1-α: 19017
UCP3: 22229"
  },
  {
    "caption": "D Quantitative real time PCR for UCP1, using RNA from BAT from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from three independent experiments (n = 6 total for each genotype). *P = 0.0018 (Student's t-test).",
    "ncbi_link": "FADD: 14082
UCP1: 22227"
  },
  {
    "caption": "E Immunoblotting of UCP1 and Tubulin (control) (top) with relative quantification (bottom), using total cell lysates of BAT from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from three independent experiments. *P = 0.0217 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "F Oxygen consumption in isolated BAT from 10-week-old male WT and FADD-D mice on a SD (n = 4 for each genotype). Data are expressed as mean ± SEM. *P = 0.0025, **P = 0.0006 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "G Quantitative real time PCR for PGC1α, C/EBPα and PPARγ, using RNA from BAT from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from two independent experiments (n = 4 total for each genotype). *P = 0.0113 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "C/EBPα: 12606
FADD: 14082
PPARγ: 19016
PGC1α: 19017"
  },
  {
    "caption": "H β-oxidation analysis of white adipocytes isolated from WT (n = 5) and FADD-D mice (n = 4). 1-14C labeled oleic acid was added to the medium containing isolated adipocytes (5×105), and 14CO2 trapped by the filter paper soaked with hyamine hydroxide was measured after a 3 h-incubation by a scintillation counter. Data are expressed as mean ± SEM. *P = 0.0022 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "I Basal and stimulated (+ 100 nM isoproterenol) lipolysis, as measured by glycerol (left) and fatty acids (right) released from explants of epididymal WAT from overnight fasted 10-week-old male WT and FADD-D mice fed a HFD (n = 4 for each genotype). Data are expressed as mean ± SEM. *P = 0.0078, **P = 0.0065, ***P = 0.0008, ^P = 0.0133, ^^P = 0.0053, ^^^P = 0.0006, ^^^^P = 0.0001, #P = 0.0082, ##P = 0.0051, ###P = 0.0009, *^P = 0.0151, *^^P = 0.0019, **^^P = 0.0005, ***^P = 0.0002 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A Quantitative real time PCR for enzymes related to lipid metabolism, using RNA from epididymalfat from 10-week-old male WT and FADD-D mice on a SD. Data are expressed as mean ± SEM from two independent experiments (n = 5 total for each genotype). *P = 0.0162, **P = 0.0105, ***P = 0.0063 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B cAMP abundance in epididymalWAT from 10-week-old male WT and FADD-D mice on a HFD (n = 4 for each genotype). Data are expressed as mean ± SEM. *P = 0.0033 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Basal and forskolin-stimulated adenylyl cyclase activity in epididymalWAT from 10-week-old male WT and FADD-D mice on a HFD (n = 4 for each genotype). Data are expressed as mean ± SEM. *P = 0.0177, *P = 0.0091 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "E Basal and stimulated (+200 nM isoproterenol) lipolysis in epididymalWAT of 10-week-old male WT and FADD-D mice (n = 4 for each genotype) treated with or without 10 μM BAY. Data are expressed as mean ± SEM. *P = 0.0019, **P = 00038, ^P = 0.0035, ^^P = 0.0053 (one-way ANOVA). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "F Basal and stimulated (+200 nM isoproterenol) lipolysis in isolated adipocytes from 10-week-old WT and FADD-D mice (n = 4 for each genotype) treated with or without 10 μM BAY. Data are expressed as mean ± SEM. *P = 0.0033, **P = 0.0051, ^P = 0.004, ^^P = 0.0057 (one-way ANOVA). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A Typical growth curves of control and ad-FADDmice maintained on a SD (left panel) or a HFD (right panel) (n = 8 for each genotype). Data are expressed as mean ± SEM. *P = 0.0435, **P =0.0371, ^P = 0.0217, #P = 0.0236, ##P = 0.0158, ###P = 0.0113 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "B Body composition by NMR to show the fat mass and fat mass ratio in control and ad-FADDmice after 10 weeks of HFD (n = 6 for each genotype). Data are expressed as mean ± SEM. *P = 0.0027, **P = 0.0012 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "C Food intake in 15-week-old male control and ad-FADDmice fed a HFD (n = 8 for each genotype).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "D and E Representative pictures of hematoxylin and eosin-stained sections of epididymalWAT from control and ad-FADDmice at 10 weeks (D) and after 10 weeks of an HFD (E) are shown. Scale bar = 50 μm. Shown are typical results from four different fields and three different experiments.F The average cross-sectional area of adipocytes in epididymalWAT is shown in the bar graph (n = 6 for each genotype). Data are expressed as mean ± SEM. *P = 0.002 (Student's t-test). NS, not statistically significant.G The distribution of adipocyte cross-sectional area in epididymalWAT of HFD-fed control or ad-FADDmice is shown in the bar graph (n = 6 for each genotype).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "H Representative pictures of hematoxylin and eosin-stained sections of brown adipose tissue from HFD-fed control and ad-FADDmice are shown. Scale bar = 50 μm. Shown are typical results from four different fields and three different experiments.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A-C HFD-fed control and ad-FADDmice were housed in a computer-controlled open-circuit indirect calorimeter to determine (A) oxygen consumption, (B) carbon dioxide production, and (C) respiratory exchange ratio (RER) during the light (8 am - 8 pm) and dark (8 pm - 8 am) periods (n = 5 for each genotype). Data are expressed as mean ± SEM. *P = 0.0379, **P = 0.0453, ***P = 0.0445 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "D The result of real-time quantitative PCR analysis for UCP1 in brown adipose tissue from HFD-fed control and ad-FADDmice is shown in the bar graph. Data are expressed as mean ± SEM from two independent experiments (n = 4 total for each genotype). *P = 0.0172 (Student's t-test).",
    "ncbi_link": "FADD: 14082
UCP1: 22227"
  },
  {
    "caption": "E Immunoblot of UCP1 and Tubulin (control) (top) in BAT from control and ad-FADDmice with relative quantification (bottom). Data are expressed as mean ± SEM from three independent experiments. *P = 0.0053 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "D Insulin-stimulated Akt phosphorylation (Ser473) in WAT, liver, and skeletal muscle of control and ad-FADD mice. The experiments were performed in triplicate.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "E Adiponectin mRNA was measured in isolated epididymal adipocytes by RT-PCR. Data are expressed as mean ± SEM from three independent experiments. *P = 0.0044 (Student's t-test).",
    "ncbi_link": "Adiponectin: 11450"
  },
  {
    "caption": "I Basal and insulin-stimulated glucose uptake in control and FADD deficient primary isolated adipocytes. Data shown are from one experiment (n = 4 for each genotype), representative of a total of two independent experiments. Results are means ± SEM. *P = 0.0073 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "J Basal and insulin-stimulated glucose uptake in 3T3L1 cells differentiated to adipocytes and infected with lentivirus containing FADD shRNA or scrambled shRNA control. Data are expressed as mean ± SEM from three independent experiments. *P = 0.0092 (Student's t-test).",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "K Basal and insulin-stimulated glucose uptake in control and FADD deficient primary isolated adipocytes treated with DMSO or 5 μM MK886. Data are expressed as mean ± SEM from four independent experiments. *P = 0.0135 (one-way ANOVA). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082"
  },
  {
    "caption": "A Relative mRNA levels of the macrophage marker F4/80 in SVCs isolated from epididymal adipose tissue. Data are expressed as mean ± SEM from four independent experiments. *P = 0.0279 (Student's t-test).",
    "ncbi_link": "F4/80: 13733"
  },
  {
    "caption": "C Relative mRNA levels of the proinflammatory M1-like macrophage marker CD11c in SVCs isolated from epididymal adipose tissue. Data are expressed as mean ± SEM from five independent experiments. *P = 0.0221 (Student's t-test).",
    "ncbi_link": "CD11c: 16411"
  },
  {
    "caption": "A Top, representative photographs of 20-week-old male ob/ob and FADD-D/ob/ob mice fed a SD. Bottom, representative photographs of their livers and epididymalWAT.",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "B Comparison of weights of WAT depots from WT, FADD-D, ob/ob and FADD-D/ob/ob mice. n = 5 for each genotype. Data are expressed as mean ± SEM. *P = 0.0007, **P = 0.0022, ***P = 0.0011, #P = 0.0009, ##P = 0.0003, ###P = 0.0027 (one-way ANOVA).",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "C Basal and stimulated lipolysis measured by fatty acid release from explants of epididymalWAT in 10-week-old male ob/ob and FADD-D/ob/ob mice fed a HFD. n = 4 for each genotype. Data are expressed as mean ± SEM. *P = 0.0003, **P = 0.001 (one-way ANOVA).",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "D cAMP level in WAT of 10-week-old male WT, FADD-D, ob/ob and FADD-D/ob/ob mice fed a HFD. n = 4 for each genotype. Data are expressed as mean ± SEM. *P = 0.0017, **P = 0.001 (one-way ANOVA).",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "E Whole-body oxygen consumption rate (VO2) during 24 hr in WT, FADD-D, ob/ob, and FADD-D/ob/ob mice fed a SD. n = 4 for each genotype. Data are expressed as mean ± SEM. *P = 0.0053, **P = 0.0025, ***P = 0.0062, ****P = 0.0011 (one-way ANOVA).",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "F Quantitative real time PCR for Dio2, PPARd and UCP1, using RNA from epididymal fat from 20-week-old male ob/ob and FADD-D/ob/ob mice fed a SD. Data are expressed as mean ± SEM from four independent experiments. *P = 0.0009, **P = 0.0015, ***P = 0.0003 (Student's t-test).",
    "ncbi_link": "Dio2: 13371
FADD: 14082
ob: 16846
PPARd: 19015
UCP1: 22227"
  },
  {
    "caption": "G Quantitative real time PCR for UCP3, PGC-1α, PPARd and CPT1, using RNA from skeletal muscle from 20-week-old male ob/ob and FADD-D/ob/ob mice fed a SD. Data are expressed as mean ± SEM from four independent experiments. *P = 0.0105, **P = 0.0033, ***P = 0.0058 (Student's t-test). NS, not statistically significant.",
    "ncbi_link": "CPT1: 12895///12894
FADD: 14082
ob: 16846
PPARd: 19015
PGC-1α: 10891
UCP3: 22229"
  },
  {
    "caption": "H Quantitative real time PCR for UCP1, PPARa, CPT1 and PGC-1α, using RNA from brown adipose fat from 20-week-old male ob/ob and FADD-D/ob/ob mice fed a SD. Data are expressed as mean ± SEM from four independent experiments. *P = 0.0012 **P = 0.0129, ***P = 0.0103, ****P = 0.0207 (Student's t-test).",
    "ncbi_link": "CPT1: 12895///12894
FADD: 14082
ob: 16846
PPARa: 19013
PGC-1α: 19017
UCP1: 22227"
  },
  {
    "caption": "I Oxidation of [1-14C] oleic acid to 14CO2by adipocytes isolated from WT, FADD-D, ob/ob, and FADD-D/ob/ob mice. Data shown are from one experiment (n = 3 for each genotype), representative of a total of two independent experiments. Results are means ± SEM. *P = 0.0031, **P = 0.0075 (one-way ANOVA). NS, not statistically significant.",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "J Immunoblot of VLCAD, LCAD, MCAD, PTL and Tubulin (control), using protein extracts from epididymal fat from 15-week-old male WT, FADD-D, ob/ob and FADD-D/ob/ob mice fed a SD. Data shown are representative of three independent experiments having similar results.",
    "ncbi_link": "FADD: 14082
ob: 16846"
  },
  {
    "caption": "(B) Epg5 protein and the wild-type copy of Epg5 are absent in Epg5−/− mice. There is an intervening lane between Epg5+/− and Epg5−/− lanes in the Western blot.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(C) Body weight curves of Epg5+/− and Epg5−/− males. Means ± SEM of 12 mice are shown.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(E) Epg5−/− males show gradually worsening limb-clasping reflexes.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(F) The hindquarters of Epg5−/− mice are completely paralyzed at 10 mo of age.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(G) Spinal deformation in an Epg5−/− male at 10 mo of age.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(H) Epg5−/− females gradually develop the limb-clasping phenotype.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(A) Nissl staining of the fifth layer of the cortex in 10-mo-old Epg5+/− and Epg5−/− mice. (B) The number of pyramidal cells in the fifth layer per millimeters squared.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(C and D) H&E staining of the hippocampus shows reduced pyramidal cell numbers in Epg5−/− mice. Means ± SEM of three mice are shown in B and D.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(E) The normally developed cerebellum in Epg5−/− mice. (F) The thickness of the molecular layer in the cerebellum in mutant and control mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(G and H) Purkinje cells, stained by calbindin, are not reduced in number in Epg5−/− mice. Means ± SEM of five mice are shown in F and H.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(I) Arrows indicate Pyknotic neurons in the anterior horn of Epg5−/−mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(J) The number of motor neurons in the spinal cord (SC) in Epg5+/− and Epg5−/−mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(K) The numbers of Nissl-stained interneurons in the spinal cord are similar in control and Epg5−/− mice. Means ± SEM of three mice are shown in J and K.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(L) Eosinophilic spheroids (arrows) accumulate in the thoracic spinal cord of Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(N) EM pictures showing degenerated axons (arrows) in the spinal cord of Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(O and P) GFAP staining in Epg5+/− and Epg5−/−mice. DCST, dorsal corticospinal tract.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(A) Levels of LC3 and p62 in brain and spinal cord extracts from Epg5+/− and Epg5−/− mice. SC, spinal cord.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(B) Polyubiquitinated proteins in detergent-soluble (S) and -insoluble (I) fractions from brain and spinal cord homogenates of Epg5+/− and Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(C) p62 aggregates and ubiquitin-positive aggregates are absent from Epg5+/− mice but dramatically accumulate and are colocalized (arrows) in Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(D-F) p62 aggregates are detected in neurons (arrows; D) and oligodendrocytes (arrows; E) but absent from astrocytes (F) in Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(G) Cytoplasmic TDP-43 aggregates accumulate in motor neurons in the anterior horn of spinal cord in Epg5−/− mice. Arrows show cytoplasmic TDP-43 aggregates. DSCT, dorsal corticospinal tract. (H) Percentages of cytoplasmic TDP-43 aggregate-positive motor neurons in the fifth layer of cortex and anterior horn of the spinal cord in Epg5+/− and Epg5−/− mice. Means ± SEM of three mice are shown. LC, lateral column. Bars, 10 µm.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(A and B) Electromyography of the gastrocnemius muscle from a 3-mo-old Epg5−/− mouse showing fibrillations (A) and positive sharp waves (B). These defects were absent in control mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(C) At 10 mo, Epg5−/−mice showed high-amplitude and long-duration action potentials when conducting MUAP tests. The blue lines show the start and end of an action potential. Dur, duration; Amp, amplitude.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(D-F) H&E staining of gastrocnemius muscles showed features of muscle degeneration in Epg5−/−mice. The arrow in E indicates centrally nucleated fibers.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(G) The transcription levels of the atrophy-related genes were up-regulated in gastrocnemius muscles of Epg5−/−mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(J) Levels of LC3-II and p62 in muscle extracts from Epg5+/− and Epg5−/− mice.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(K) Percentage of p62 aggregate-positive myofibers in Epg5+/− and Epg5−/− mice. Means ± SEM of three mice are shown.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(L) Accumulation and colocalization of p62 and ubiquitin aggregates in the gastrocnemius muscles of Epg5−/− mice but not controls. Bars: (D-F and L) 10 µm; (H and I) 1 µm.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(A) Number of LC3 puncta in Epg5+/− (control) and Epg5−/− MEFs.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(B) Western blot showing levels of LC3-I and LC3-II in control and Epg5−/− MEFs upon indicated treatment (Starv., starvation; Rapa., rapamycin; Bafilo., bafilomycin A1).",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(D) Colocalization ratio of LC3 and LAMP-1 in control and Epg5−/− MEFs. 50 cells were examined per time point in A and D.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(E) Colocalization of LC3 puncta and lysosomes in control and Epg5−/− MEFs 4 h after starvation.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(F) Under nutrient repletion conditions, almost no autophagic elements are detected in Epg5+/− MEFs. RER, rough ER; M, mitochondrion; N, nucleus. The arrowhead indicates a vacuole with a late residual body-like appearance (aAV-III). (G) Under nutrient repletion conditions, Epg5−/− MEFs accumulate a large number of autophagic vacuoles. Red arrow, a likely autophagosome; red arrowheads, complex vacuoles of the aAV-I type; white arrowheads, aAV-II vacuoles",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(H and I) High magnification of autophagic elements in unstarved Epg5−/− MEFs. (H) The red arrow indicates a complex autophagic vacuole containing multilayered membrane structures (white arrowheads) and a lipid-like region (L). (I) The red arrow indicates an autophagosome containing cytoplasm and ribosomes. The red arrowhead points to an autophagosome containing a mitochondrion and cytoplasmic material with membranous structures. The white arrow shows an aAV-III vacuole.",
    "ncbi_link": "Epg5: 100502841"
  },
  {
    "caption": "(J) Compared with control cells, Rab5-labeled early endosomes are significantly enlarged in Epg5 siRNA-treated cells.",
    "ncbi_link": "Epg5: 57724"
  },
  {
    "caption": "(K and L) EGFR degradation in control and Epg5 knockdown cells.",
    "ncbi_link": "Epg5: 57724"
  },
  {
    "caption": "(M and N) Distribution of Alexa Fluor 488-conjugated transferrin at different time points in control siRNA- and Epg5 siRNA-treated cells. Higher magnification views are shown in the insets. Error bars indicate SEMs.",
    "ncbi_link": "Epg5: 57724"
  },
  {
    "caption": "Strong nuclear p53 signal in immunostainings of HGSOC organoids is indicative of a gain-of-function TP53 mutation. Scale bars: 100 µm (Tissue) and 50 µm (Organoid).",
    "ncbi_link": "TP53: 7157"
  },
  {
    "caption": "Heat map of differentially expressed genes between cancer and healthy tissue/organoids reveals upregulation of several HGSOC biomarkers and reduction of FT differentiation markers in the cancer samples. Differential expression determined by single-color microarray for 8 different patient samples was significant for all genes with p < 0.05 except for OVGP1 and TOP2A in organoids.",
    "ncbi_link": "OVGP1: 5016
TOP2A: 7153"
  },
  {
    "caption": "Experimental approach for genetic manipulation of FT epithelial cells (FTECs). FTECs were sequentially transduced in 2D culture with replication-deficient viruses containing specific shRNAs and different selection markers. After sorting cells were seeded in Matrigel for organoid formation. Scale bars: 2 cm (tissue), 200 µm (2D culture) and 500 µm (3D culture). Confirmation of robust knockdowns of p53, PTEN and RB in FT organoids on RNA and protein level. Relative mRNA levels were normalized to the WT mRNA level and are given as the mean ±SEM from 3 different donors. A representative western blot from one donor is depicted. RNA as well as protein samples were taken at passage 1 or 2 of each organoid line. KD - Knockdown, Vec Ctrl - Vector Control, WT- Wild type",
    "ncbi_link": "PTEN: 5728
RB: 5925
p53: 7157"
  },
  {
    "caption": "Cyclin E1 overexpression as a downstream effect of RB knockdown was confirmed by western blot analysis.",
    "ncbi_link": "RB: 5925"
  },
  {
    "caption": "Confirmation of robust knockdowns of p53, PTEN and RB in FT organoids on RNA and protein level. Relative mRNA levels were normalized to the WT mRNA level and are given as the mean ±SEM from 3 different donors. A representative western blot from one donor is depicted. RNA as well as protein samples were taken at passage 1 or 2 of each organoid line. KD - Knockdown, Vec Ctrl - Vector Control, WT- Wild type Cyclin E1 overexpression as a downstream effect of RB knockdown was confirmed by western blot analysis. Presence of ciliated cells (arrowheads), as revealed by immunostaining against detyrosinated Tubulin (dtyrTub) in triple KD organoids, proves capacity for terminal differentiation. Scale bar: 50µm.",
    "ncbi_link": "PTEN: 5728
RB: 5925
p53: 7157"
  },
  {
    "caption": "Triple KD (p53/PTEN/RB) organoids are characterized by a HGSOC gene expression signature as revealed by microarray analysis comparing WT and KD organoids grown in either OCM or FTM. Differential expression determined by dual-color microarray for 2 biological replicates was significant for all genes with p < 0.00005.",
    "ncbi_link": "PTEN: 5728
RB: 5925
p53: 7157"
  },
  {
    "caption": "Differential expression of stemness- and differentiation-related genes of triple KD organoids grown in OCM vs. FTM. Fold-changes were derived from microarray data and indicate and an increase in stemness (CD133, SOX2, MYCN) and a drop in differentiation (OVGP1, PGR, FOXJ1) under OCM conditions. Differential expression determined by dual-color microarray for 2 biological replicates was significant for all genes with p < 0.05.",
    "ncbi_link": "FOXJ1: 2302
MYCN: 4613
OVGP1: 5016
PGR: 5241
CD133: 8842
SOX2: 6657"
  },
  {
    "caption": "FOXJ1 expression determined by qPCR was significantly diminished in triple KD organoids grown in OCM compared to FTM, suggesting a decrease in differentiation capacity. Data represent the mean ±SEM from technical triplicates for two independent knockdown cultures.",
    "ncbi_link": "FOXJ1: 2302"
  },
  {
    "caption": "Comparative analysis of microarray data revealed consistent up-regulation of MYCN, the canonical Wnt inhibitors KREMEN2 and DKK3 as well as differentiation marker FOXJ1, AR and PGR in HGSOC cancer organoids as well as triple KD FT organoids. Differential expression was determined either by single-color microarray for the cancer samples (8 replicates) or dual-color microarray for the knockdowns (2 replicates) and is significant for all genes with p < 0.05.",
    "ncbi_link": "AR: 367
DKK3: 27122
FOXJ1: 2302
KREMEN2: 79412
MYCN: 4613
PGR: 5241"
  },
  {
    "caption": "Transcriptional induction of MYCN is confirmed by qPCR for three patients between cancer organoids and normal FT organoids as well as triple KD organoids grown in OCM vs. FTM conditions. Depicted is the mean ±SEM of the normalized MYCN mRNA expression level of three biological replicates (n=3). ** p < 0.01, *** p < 0.001, two-sided Student`s t-test.",
    "ncbi_link": "MYCN: 4613"
  },
  {
    "caption": "FOXJ1 expression was upregulated in HGSOC organoids in FTM compared to OCM as shown by qPCR analysis of 3 different patient samples. Data represent the mean ±SEM of technical triplicates.",
    "ncbi_link": "FOXJ1: 2302"
  },
  {
    "caption": "A. qPCR analysis shows loss of Setd1b in forebrain regions while levels in the cerebellum are not affected (CA: Control, n = 6; cKO, n = 6. DG: Control, n = 6; cKO, n = 6. Cortex: Control, n = 7; cKO, n = 7. Cerebellum: Control, n = 4; cKO, n = 4). * p-value < 0.05 (Student t-test).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "B. Immunoblot analysis shows loss of Setd1b protein in the hippocampus of Setd1b cKO mice (Control, n = 4; cKO, n = 4). ** p-value < 0.01 (Student t-test).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "C. Immunohistochemical staining (upper level) for marker proteins of neuronal integrity and quantification (lower panel) show no difference in control and Setd1b cKO mice (NeuN: Control, n = 6; cKO, n = 6; Student t-test p-value = 0.57. MAP2: Control, n = 4; cKO, n = 4; Student t-test p-value = 0.72. Iba1: Control, n = 5; cKO, n = 5; Student t-test p-value = 0.8. Gfap: Control, n = 5; cKO, n = 5; Student t-test p-value = 0.09.). Scale bar: 100 µm.",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "D. Average speed (left panel) and percent time spent in the center (right panel) during exposure to the open field test was similar in control and Setd1b cKO mice (Average speed: Control, n = 15; cKO, n = 15; Student t-test p-value = 0.075. Time spent in center: Control, n = 15; cKO, n = 15; Student t-test p-value = 0.96).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "E. Short term memory was not different between control and Setd1b cKO mice as indicated by similar percent of alternations in the Y-maze test (Control, n = 15; cKO, n = 15; Student t-test p-value = 0.3).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "G. Escape latency during water maze training indicated severe learning impairment in Setd1b cKO mice (Control: n = 15, cKO: n = 15. Repeated measures ANOVA, genotype effect: F (1,28) = 82.34, **** p-value < 0.0001).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "H. Plots showing the specific search strategies during water maze training. Note the failure of Setd1b cKO mice to adopt hippocampus-dependent search strategies. I. The cognitive score calculated on the basis of the hippocampal search strategies reflects severe memory impairment in Setd1b cKO mice (Student t-test: *** p-value < 0.001).",
    "ncbi_link": "Setd1b: 208043"
  },
  {
    "caption": "F. Left panel shows representative images of RNAscope performed for Kmt2a, Kmt2b and Setd1b. Right panel shows a bar chart quantifying the dots/cell (n = 1500 cells from 2 mice) indicative of the corresponding expression level. Kmt2a expression was significantly higher when compared to Kmt2b or Setd1b (*** p-value < 0,0001, Student t-test).",
    "ncbi_link": "Kmt2a: 214162
Kmt2b: 75410
Setd1b: 208043"
  },
  {
    "caption": "Heatmap of IFNG, GZMB and PRF1 gene expression in COVID-19 patients. Average expression values were centered and scaled. Red indicates a higher expression and blue indicates a lower expression.",
    "ncbi_link": "GZMB: 3002
IFNG: 3458
PRF1: 5551"
  },
  {
    "caption": "LN229 were transfected with siNT, siNoxa 1, siNoxa 2 or BAK-siRNA for 72h. Thereafter, cells were treated with the combination treatment of 1 µM ABT263 and 20 µM LXR623 for another 24h. After conclusion of the treatment, cells were harvested, fixed, stained with propidium iodide and analyzed by flow cytometry for DNA - fragmentation.",
    "ncbi_link": "BAK: 578
Noxa: 5366"
  },
  {
    "caption": "U87 cells were transfected with non-targeting siRNA (n.t.-siRNA), ATF3-siRNA, ATF4 siRNA or the combination of both ATF4 and ATF3 siRNAs. After 48h, cells were treated with LXR623, whole cell protein lysates were harvested and analyzed by capillary electrophoresis for the expression of ATF3, ATF4, Noxa and Vinculin.",
    "ncbi_link": "ATF3: 467
ATF4: 468"
  },
  {
    "caption": "U87 cells transduced with non-targeting or LXRβ shRNA were treated with vehicle or 20 µM LXR623 for 24h. Thereafter, extracellular flux analysis was performed in the context of a mitochondrial stress assay. From this assay, basal respiration and coupled respiration was calculated (M-N).",
    "ncbi_link": "LXRβ: 7376"
  },
  {
    "caption": "U87 cells transduced with non-targeting or LXRβ shRNA were treated with vehicle or 20 µM LXR623 for 24h. RNA and protein were collected and analyzed for the expression of LXRβ mRNA (O) or LXRβ protein by capillary electrophoresis (P). Shown are means and SD (n = 5). Statistical significance was determined by two-sided student's t.test.",
    "ncbi_link": "LXRβ: 7376"
  },
  {
    "caption": "1x106 HCT116 colon carcinoma cells were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100-200 mg/kg), ABT263 (100 mg/kg) or both agents (3 days per week for 1.5 weeks. Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.022, **p=0.0063, ****p<0.0001. Statistical significance was determined by one-way ANOVA. B, E, GBM43 PDXs were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100 mg/kg), ABT263 (75 mg/kg) or both agents (3 days per week for 1.5 weeks). Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.022, **p=0.0031. Statistical significance was determined by one-way ANOVA. C, F, A375 BRAF V600E mutated melanomas were implanted subcutaneously. Animals were treated intraperitoneally with vehicle, LXR623 (100 mg/kg), ABT263 (75 mg/kg) or both agents (3 days per week for 1.5 weeks). Tumor growth curves show the development of tumor size for each treatment group. Scatter plots display the quantitative representation of the tumor size among the different treatments toward the end of the experiment. Shown are means and SD (n ≥ 5). *p=0.0109 (GW3965 vs Combination), *p=0.0166 (ABT263 vs Combination), **p=0.0047. Statistical significance was determined by one-way ANOVA. ",
    "ncbi_link": "BRAF: 673"
  },
  {
    "caption": "Mass chromatograms of the nucleosides, Cm (Q1/Q3=258.1/112.1), Gm (Q1/Q3=298.1/152.1) and A (Q1/Q3=268.1/136.2) of tRNAPhe(GAA) isolated from WT, ftsj1 KO and wdr6 KO cells. Target peaks are indicated by black triangles. Cm, 2'-O-methylcytidine; Gm, 2'-O-methylguanosine; Q1/Q3: the mass of the precursor ion and the mass of the product ion.",
    "ncbi_link": "ftsj1: 24140
wdr6: 11180"
  },
  {
    "caption": "Mass chromatograms of the nucleosides m1G (Q1/Q3=298.1/166.1), m7G (Q1/Q3=298.1/166.1) and m2G (Q1/Q3=298.1/166.1), o2yW (Q1/Q3=541.2/409.0), m5C (Q1/Q3=258.1/126.1) and A (Q1/Q3=268.1/136.2) of tRNAPhe(GAA) isolated from WT, ftsj1 KO and wdr6 KO cells. Target peaks are indicated by black triangles. m2G, 2-methylguanosine; D, dihydrouridine; m22G, N2,N2-dimethylguanosine; m5C, 5-methylcytidine; m7G, 7-methylguanosine; m5U, 5-methyluridine; m1A: 1-methyladenosine; ψ: pseudouridine; o2yW, peroxywybutosine. Q1/Q3: the mass of the precursor ion and the mass of the product ion. Combined the retention time of standard product, we marked the o2yW in Figure 3G. Considering the change of this peak area was consistent with that of o2yW, we speculated the other peak was generated by the intermediate product of o2yW with nature isotope labelled.",
    "ncbi_link": "ftsj1: 24140
wdr6: 11180"
  },
  {
    "caption": "(B, C) Quantification of the Cm/A and Gm/A of tRNAPhe(GAA), △ftsj1_tRNAPhe(GAA), and m1G37_tRNAPhe(GAA) after incubation with FTSJ1, WDR6, and FTSJ1-WDR6 by UPLC-MS/MS analysis, respectively. Error bars represent the standard deviation of three independent experiments. n.d., not detected.",
    "ncbi_link": "ftsj1: 24140"
  },
  {
    "caption": "The representative graphs for quantification of the expected Nm32/A% and Nm34/A% ratios of G37-tRNAPhe(GAA), tRNALeu(UAA), tRNATrp(CCA), tRNAArg(ACG), tRNAArg(UCG), and A37-tRNAMet(CAU), which were isolated from WT, ftsj1 KO, and wdr6 KO cells by UPLC-MS/MS analysis. Error bars represent the standard deviation of three independent experiments. p values were determined using two-tailed Student's t-test for paired samples. ***p < 0.001. n.s., no significance. n.d., not detected.",
    "ncbi_link": "ftsj1: 24140
wdr6: 11180"
  },
  {
    "caption": "(A, B) The growth curve of WT and two ftsj1 KO HEK293T cell lines under normal culture or in the culture condition with 0.2 mg/mL paromomycin assayed by cell counting kit-8 proliferation analysis.",
    "ncbi_link": "ftsj1: 24140"
  },
  {
    "caption": "(E, F) The growth curve of ftsj1 KO cells with or without overexpressing tRNAPhe(GAA) under normal culture or with 0.2 mg/mL paromomycin.",
    "ncbi_link": "ftsj1: 24140"
  },
  {
    "caption": "(A) expression of FUS does not alter expression of VAPB, PTPIP51 or mitofusin-2 (MFN2) in transfected NSC34 cells. Immunoblots of NSC34 cells transfected with EGFP as a control (CTRL), or wild-type or mutant EGFP-FUS. Transfected cells were purified via EGFP using a cell sorter and the samples probed on immunoblots as indicated. On the FUS immunoblot, samples were probed with FUS antibody to show endogenous and transfected proteins; tubulin is shown as a loading control.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(B) representative electron microscopy of ER-mitochondria associations in NSC34 cells transfected with control EGFP vector (CTRL), EGFP-FUS, EGFP-FUSR521C or EGFP-FUSR518K as indicated; arrowheads with loops show regions of association. Scale bar=200 nm. Bar chart shows % of the mitochondrial surface closely apposed to ER in the different samples. Data were analysed by one-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test. N=27-30 cells and 247-424 mitochondria, error bars are s.e.m.; ***p<0.001.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(C and D) siRNA loss of FUS does not affect ER-mitochondria associations or alter expression of VAPB, PTPIP51 or mitofusin-2 (MFN2) in NSC34 cells. (C) immunoblots of cells either mock transfected or treated with control (CTRL) or FUS siRNAs; GAPDH is shown as a loading control.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(C and D) siRNA loss of FUS does not affect ER-mitochondria associations or alter expression of VAPB, PTPIP51 or mitofusin-2 (MFN2) in NSC34 cells. (D) representative electron microscopy of ER-mitochondria associations in control (CTRL) and FUS siRNA treated cells. Arrowheads with loops show regions of association. Scale bar=200 nm. Data analysed by unpaired t-test. N=27-28 cells and 193-202 mitochondria.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(A) FU-induced reductions in ER-mitochondria associations can be detected using SIM. NSC34 cells were transfected with either EGFP control vector, EGFP-FUS, EGFP-FUSR521C or EGFP-FUSR518K and immunostained for TOM20 and PDI to label mitochondria (Mito) and ER respectively; FUS were detected via their EGFP tags. Merge (ZOOM) show zoomed images of boxed regions and co-localisation shows co-localised pixels. Scale bar=2 m. Bar chart shows ER-mitochondria co-localisation (Manders coefficient) normalized to control in the different samples. Data were analysed by one-way ANOVA with Tukey's post-hoc test. 10-14 cells were analysed per condition from 3 independent experiments; error bars are s.e.m., **p<0.01 and ***p<0.001.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(B) ER-mitochondria associations and the VAPB-PTPIP51 interaction are disrupted by wild-type and ALS/FTD mutant FUS. NSC34 cells were transfected with EGFP control vector (CTRL), EGFP-FUS, EGFP-FUSR521C or EGFP-FUSR518K and proximity ligation assays performed using VAPB and PTPIP51 antibodies. FUS were detected via their EGFP tags. Scale bar=10 m. Bar chart shows relative number of proximity ligation assay signals/cell. Data were analysed by one-way ANOVA and Tukey's post-hoc test; n=47-53 cells from 5 experiments. Error bars are s.e.m.; ***p<0.001.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(C) overexpression of FUS reduces the binding of VAPB to PTPIP51 in transfected cells. Cells were transfected as indicated with either control empty vector (CTRL), HA-PTPIP51+CTRL, or HA-PTPIP51+ either EGFP-FUS, EGFP-FUSR521C or EGFP-FUSR518K. PTPIP51 was immunoprecipitated using the HA tag and the amounts of endogenous bound VAPB detected by immunoblotting. Both inputs and immunoprecipitations (IP) are shown and no immunoprecipitating VAPB signals were obtained in the absence of HA-PTPIP51. Bar chart shows relative levels of VAPB bound to PTPIP51 in the immunoprecipitations following quantification of signals from immunoblots. VAPB signals were normalized to immunoprecipitated PTPIP51-HA signals.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(A) overexpression of FUS does not affect expression of VAPB, PTPIP51 or mitofusin-2. Immunoblots of spinal cord proteins from three 10 week old FUS transgenic mice and three age-matched littermates are shown; FUS was detected via its HA-tag. Tubulin was used as a loading control.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(B) representative electron microscopy of ER-mitochondria associations in lumbar spinal cord motor neurons of FUS transgenic mice and their non-transgenic littermates; arrowheads with loops show regions of association. Scale bar is 200 nm. Bar chart shows % of mitochondrial surface closely apposed to ER in the two samples. Data were analysed by unpaired t-test. N=67-88 cells and 438-749 mitochondria, error bars are s.e.m.; ***p<0.001.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(C) ER-mitochondria associations and the VAPB-PTPIP51 interaction are disrupted in lumbar motor neurons in spinal cords of FUS transgenic mice. Representative images of proximity ligation signals in 11 week old FUS and non-transgenic (NTg) littermate mice. Data were analysed by unpaired t-test; N=40 cells from 3 FUS and 3 non-transgenic littermates (age 10 weeks).",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(A and B) FUS disrupts Ca2+ homeostasis. HEK293 cells were transfected with M3R and either control vector (CTRL), FUS, FUSR521C or FUSR518K as indicated. Release of ERCa2+ was induced by treatment of cells with OxoM. (A) shows cytosolicCa2+ levels with representative Fluo4 fluorescence traces on the left and normalized peak values on the right. Fluo4 fluorescence shows a transient increase in cytosolicCa2+ levels upon OxoM treatment but compared to control, wild-type and mutant FUS all increase peak cytosolicCa2+ levels. (B) shows mitochondrialCa2+ levels with representative Rhod2 fluorescence traces on the left and normalized peak values on the right. Data were analysed by one-way ANOVA and Tukey's post hoc test. (A) N=49-52 cells from 3 experiments; (B) N=50-52 cells from 5 experiments, error bars are s.e.m.; *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "M3R: 12671
FUS: 2521"
  },
  {
    "caption": "(C) FUS reduces mitochondrial ATP production. ATP levels were measured in NSC34 cells transfected with the ATP indicator AT1.03 and either control vector (CTRL), HA-FUS, HA-FUSR521C or HA-FUSR518K. Cells were imaged in time-lapse prior to and after KCN treatment to inhibit oxidative phosphorylation. Representative traces of YFP/CFP ratios are shown for the different samples; initial YFP/CFP ratios prior to KCN treatment and those after KCN treatment are indicated. The fall in YFP/CFP ratios correlates with ATP produced by oxidative phosphorylation. Bar chart shows relative ATP levels produced by oxidative phosphorylation (OXPHOS) in the different samples.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(A) cells were transfected with either control vector (CTRL), HA-FUS, HA-FUSR521C or HA FUSR518K and the samples probed on immunoblots for GSK-3 phosphorylated on serine-9 (GSK-3-S9), total GSK-3, FUS (using FUS antibody) and tubulin as a loading control. Phosphorylation of GSK-3 serine-9 is the principal mechanism for regulating its activity; serine-9 phosphorylation inhibits GSK-3 activity. Bar chart shows relative levels of GSK-3β serine-9 phosphorylation following quantification of signals from immunoblots and normalization to total GSK-3β signals. Data were analysed by one-way ANOVA and Tukey's post hoc test. N=4, error bars are s.e.m; *p<0.05.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(B) immunoblots of total and serine-9 phosphorylated GSK-3 in spinal cords from three 10 week-old FUS transgenic mice and their non-transgenic littermates. Samples were probed for tubulin as a loading control. Bar chart shows relative levels of GSK-3β serine-9 phosphorylation following quantification of signals from immunoblots and normalization to total GSK-3β signals. Data were analysed by unpaired t-test, error bars are s.e.m.; *p<0.05.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(C) cytosolic FUS activates GSK-3 more potently than wild type FUS. Cells were transfected with EGFP control, EGFP-FUS or EGFP-FUS lacking its C-terminal nuclear localization signal (FUSC). Samples were probed on immunoblots for total GSK-3, GSK-3 phosphorylated on serine-9, FUS (using EGFP antibody) and tubulin as a loading control. Bar chart shows relative levels of GSK-3β serine-9 phosphorylation following quantification of signals from immunoblots and normalization to total GSK-3β signals. Data were analysed by one-way ANOVA and Tukey's post hoc test. N=3, error bars are s.e.m.; **p<0.01, ***p<0.001.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "(D) cytosolic FUS reduces the VAPB-PTPIP51 interaction more potently than wild type FUS. Cells were transfected with PTPIP51-HA and either EGFP control, EGFP-FUS or EGFP-FUSC. PTPIP51 was immunoprecipitated using the HA tag and bound endogenous VAPB detected by immunoblotting. Both inputs and immunoprecipitations (IP) are shown. FUS was detected using EGFP antibody. Bar chart shows relative levels of VAPB bound to PTPIP51 in the immunoprecipitations following quantification of signals from immunoblots. VAPB signals were normalized to immunoprecipitated PTPIP51-HA signals.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "Representative electron microscopy of ER-mitochondria associations in NSC34 cells transfected with EGFP-FUS, EGFP-FUSR521C or EGFP-FUSR518K and treated with vehicle or 1 mM AR-A014418 for 16 hours. Arrowheads with loops show regions of association; scale bar=200 nm. Bar charts shows % of the mitochondrial surface closely apposed to ER in the different samples.",
    "ncbi_link": "FUS: 233908"
  },
  {
    "caption": "HEK293 cells were transfected with M3R and either control vector (CTRL), FUS, FUSR521C or FUSR518K and then treated with vehicle (DMSO) or 1 M AR-A014418 for 16 hours as indicated. Release of ER Ca2+ was induced by treatment of cells with OxoM. Representative Rhod2 fluorescence traces showing mitochondrial Ca2+ are shown along with bar chart displaying normalized peak values.",
    "ncbi_link": "M3R: 12671
FUS: 2521"
  },
  {
    "caption": "B) Expression of the 21U sensor (left) and DAPI staining (right) of gonad arms in the indicated genetic backgrounds. Gonads are outlined by a dashed line. The mCherry signal is represented in pseudo-colours [LUT fire (ImageJ)] to reflect differences in the intensity of the signal. Number of animals analysed and with indicated phenotype are given in the panel. Animals not showing the activation of the 21U sensor(+) were still silenced, and animals that did not show the silenced 21U sensor(RNAe) state were expressing weakly, comparable to the 21U sensor(+). Scale bar: 25 μm.",
    "ncbi_link": "21U: "
  },
  {
    "caption": "C) Tc1 reversion assay in different genetic backgrounds. All the strains tested carried the unc-22::Tc1(st136) allele. Tc1 excision can result in restoration of unc-22 function, which can be scored visually. Negative control = unc-22::Tc1(st136) in a wild type background; positive control = wago-1/-2/-3. Two independent experiments per strain are represented.",
    "ncbi_link": "Tc1: 
unc-22: 178135
wago-1: 172463"
  },
  {
    "caption": "D) Crossing scheme to address the re-initiation of silencing of the 21U sensor. A mut-7 mutant male expressing the 21U sensor is crossed with either a wild type (left), prg-1 (middle) or pid-2 (right) mutant hermaphrodite. Their F1 offspring was scored for expression of the 21U sensor by microscopy. Three states of expression were scored, and represented in a pie chart. The three expression states are exemplified by representative images at the bottom: OFF (left), FAINT (right) or ON (middle). DIC images are shown above the fluorescence panels. Gonads are outlined by a dashed line. Scale bar: 25 µm.",
    "ncbi_link": "21U: 
mut-7: 176347
pid-2: 171599
prg-1: 172515"
  },
  {
    "caption": "E) Crossing scheme to address if maternal 21U RNAs are sufficient to re-initiate the silencing of the 21U sensor. A pid-1 mutant male expressing the 21U sensor is crossed with a hermaphrodite, heterozygous for the same mutation. All their F1 offspring inherit a pool of 21U RNAs from the hermaphrodite, but in 50% of the F1, which is pid-1 homozygous mutant, no zygotic PID-1 is present, hence no zygotic 21U RNAs can be made. The silencing or expression of the 21U sensor in the pid-1 homozygous mutant F1 has been scored by microscopy, and depicted in a pie chart. At the bottom, a representative image of an animal carrying a silenced 21U sensor (lower: mCherry signal; upper: DAPI staining) in pid-1 mutant offspring. Gonads are outlined by a dashed line. Scale bar: 25 μm.",
    "ncbi_link": "21U: 
pid-1: 184627
PID-1: 184627"
  },
  {
    "caption": "F) Crossing scheme to test the role of PID-2 in re-initiating the silencing of the 21U sensor, mediated by maternally provided 21U RNAs only. The expression of the 21U sensor in the F1 has been scored by microscopy, and depicted in a pie chart. White arrow heads indicate the many arrayed oocytes, typical of a feminized germline. DIC and fluorescence image of a representative animal are shown at the bottom. Gonads are outlined by a dashed line. Scale bar: 25 μm.",
    "ncbi_link": "21U: 
PID-2: 171599"
  },
  {
    "caption": "The 22G RNAs mapping to the 21U sensor transgene were identified from small RNA sequencing data, and read density was plotted over the transgene, which is schematically depicted at the bottom. The aggregated results of three replicates is shown for each indicated genotype in the different panels. The shading, in grey, represents the standard deviation of the read density from the three replicates. (+) means that the sensor was detectably expressed. (RNAe) means that the sensor was crossed into the respective mutant background in an RNAe state (i.e. its silencing was PRG-1-independent), and its expression remained undetectable by microscopy.",
    "ncbi_link": "21U: 
22G RNAs: 
PRG-1: 172515"
  },
  {
    "caption": "A) MA-plot of log2 fold changes (Y-axis) versus the mean of normalized counts of 22G RNAs (X-axis) for pid-2(xf23) mutants, compared to wild type. Red dots: genes with adjusted p-value < 0.05 and fold-change > 2. Blue dots: genes with adjusted p-value < 0.05 and fold-change < -2.",
    "ncbi_link": "22G RNAs: 
pid-2: 171599"
  },
  {
    "caption": "B) Heatmap displaying overlap significance between different gene sets and genes that either up- or down-regulated in pid-2(xf23) mutants. Significance was tested with Fisher's exact test and p-values adjusted with the Benjamini-Hochberg Procedure. Colour scheme represents the odds ratio of overlaps representing the strength of association. N.S.: not significant.",
    "ncbi_link": "pid-2: 171599"
  },
  {
    "caption": "C-D) Cumulative 22G coverage along the gene body of Mutator and CSR-1 targets. Values represent 22G coverage normalized to the total coverage of each gene, for wild type (N2) and pid-2(xf23) mutants. The lines represent the average of biological replicates, whereas the shading represents the standard deviation of biological replicates. a.u.: arbitrary units.",
    "ncbi_link": "CSR-1: 177591
pid-2: 171599"
  },
  {
    "caption": "A) Expression of the 21U sensor in the indicated genetic backgrounds. Gonads are outlined by a dashed line. The mCherry signal is represented in pseudo-colours [LUT fire (ImageJ)] to reflect differences in the intensity of the signal. The panels on the right are DIC images of the respective animals. Scale bar: 25 μm.",
    "ncbi_link": "21U: "
  },
  {
    "caption": "B) 22G RNA coverage of the 21U sensor(RNAe) in the indicated genetic backgrounds.",
    "ncbi_link": "21U: 
22G RNA: "
  },
  {
    "caption": "C) MA-plot of log2 fold changes (on the Y-axis) versus the mean of normalized counts of 22G RNAs (on the X-axis) for pid-4 mutants, compared to wild type. Red dots: genes with adjusted p-value < 0.05 and fold-change > 2. Blue dots: genes with adjusted p-value < 0.05 and fold-change < -2.",
    "ncbi_link": "22G RNAs: 
pid-4: 189170"
  },
  {
    "caption": "D) Heatmap displaying overlap significance between different gene sets and genes that either up- or down-regulated in pid-4 mutants. Colour scheme represents the odds ratio of overlaps representing the strength of association.",
    "ncbi_link": "pid-4: 189170"
  },
  {
    "caption": "MA-plot of log2 fold changes (on the Y-axis) versus the mean of normalized counts of 22G RNAs (on the X-axis) , compared to wild type. Red dots: genes with adjusted p-value < 0.05 and fold-change > 2. Blue dots: genes with adjusted p-value < 0.05 and fold-change < -2. E) for pid-5 mutant",
    "ncbi_link": "22G RNAs: 
pid-5: 178819"
  },
  {
    "caption": "Heatmap displaying overlap significance between different gene sets and genes that either up- or down-regulated in F) pid-5 mutant",
    "ncbi_link": "pid-5: 178819"
  },
  {
    "caption": "MA-plot of log2 fold changes (on the Y-axis) versus the mean of normalized counts of 22G RNAs (on the X-axis) compared to wild type. Red dots: genes with adjusted p-value < 0.05 and fold-change > 2. Blue dots: genes with adjusted p-value < 0.05 and fold-change < -2. G) for pid-4;pid-5 double mutant",
    "ncbi_link": "22G RNAs: 
pid-4: 189170
pid-5: 178819"
  },
  {
    "caption": "Heatmap displaying overlap significance between different gene sets and genes that either up- or down-regulated in H) pid-4;pid-5 double mutant",
    "ncbi_link": "pid-4: 189170
pid-5: 178819"
  },
  {
    "caption": "A-E) Expression of 3xFLAG::GFP::ZNFX-1 and PGL-1::mTagRFP-T in a wild type (A), pid-2 (B), pid-4;pid-5 (C), pid-4 (D), and pid-5 (E) mutant backgrounds. The indicated dashed boxes reflect zoom-ins on specific nuclei to better visualize the granules, and their overlaps. One L4 gonad is shown. Arrow heads indicate individual condensates. Scale bar: 25 µm. F) Quantification of the ratio Z / P granules in wild type, pid-2, pid-4/-5, pid-4 and pid-5 mutant backgrounds. The number of granules is indicated in brackets, next to the genotype. ",
    "ncbi_link": "pid-2: 171599
pid-4: 189170
pid-5: 178819"
  },
  {
    "caption": "Expression of PID-4::mTagRFP-T (G) together with 3xFLAG::GFP::ZNFX-1, a Z granule marker, in a pid-2 mutant background. The indicated dashed boxes reflect zoom-ins on specific nuclei to better visualize the granules, and their overlaps. One L4 gonad is shown for each animal. Scale bar: 25 µm.",
    "ncbi_link": "pid-2: 171599"
  },
  {
    "caption": "Expression of PID-4::mTagRFP-T H) together with 3xFLAG::GFP::ZNFX-1, a Z granule marker, in a pid-2 mutant background. The indicated dashed boxes reflect zoom-ins on specific nuclei to better visualize the granules, and their overlaps. One L4 gonad is shown for each animal. Scale bar: 25 µm.",
    "ncbi_link": "pid-2: 171599"
  },
  {
    "caption": "(A and B) ARPE-19 cells were transfected with siRNA duplexes to raptor, RagA+B, p18, or nontarget. 60 h after transfection, cells were infected with adenovirus expressing either TFEB-FLAG-WT (A) or TFEB-FLAG-S211A (B). 12 h later, cells were fixed, permeabilized with 0.2% Triton X-100, and double stained with antibodies against FLAG (used to detect TFEB) and mTOR. Bars, 10 µm. (C) Quantification of A. (D) Quantification of B. Values are means ± SD of three independent experiments. ***, P < 0.001.",
    "ncbi_link": "p18: 55004
raptor: 57521
RagA: 10670
TFEB: 7942"
  },
  {
    "caption": "(D) Immunoblotting analysis of coimmunoprecipitated TFEB-FLAG-S211A with Rag heterodimers. IP, immunoprecipitation.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A) ARPE-19 cells were infected with adenovirus expressing TFEB-FLAG-WT. 16 h later, cells were incubated with 250 nM Torin-1 for 1 h or starved in serum- and amino acid-free medium for 3 h. Cells were then fixed, permeabilized with 0.2% saponin, and double stained with antibodies against TFEB (used to detect recombinant TFEB) and Lamp1.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(B) ARPE-19 cells were infected with adenovirus expressing TFEB-FLAG-S211A. 12 h later, cells were starved in serum- and amino acid-free medium for 4 h (starvation) or kept in complete medium (control). Cells were then fixed, permeabilized with 0.2% Triton X-100, and stained with antibodies against FLAG (used to detect TFEB-S211A).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A and B) ARPE-19 cells were transfected with either active or inactive RagB/D heterodimers and infected with adenovirus expressing TFEB-FLAG-WT (A) or TFEB-FLAG-S211A (B). After 12 h, cells were double stained with antibodies against FLAG and GST (used to detect TFEB or Rag proteins, respectively). (C) Quantification of TFEB-WT nuclear localization from A. (D) Quantification of TFEB-S211A lysosomal localization from B.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A) Summary of the nuclear and lysosomal distribution of several TFEB amino acid and deletion mutants in ARPE-19 cells treated with either DMSO or Torin-1.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(B) ARPE-19 cells were nucleofected with the indicated Rag- and TFEB-expressing plasmids. After 12 h, cell lysates were immunoprecipitated with the anti-FLAG antibody and analyzed by immunoblotting with antibodies against FLAG and GST (used to detect TFEB and Rag proteins, respectively).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(C) FLAG-tagged TFEB-WT or TFEB deletion mutants were immunoprecipitated with the anti-FLAG antibody and analyzed by immunoblotting with antibodies against FLAG, 14-3-3 binding motif, or 14-3-3.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(D) Immunofluorescence confocal microscopy showing the subcellular distribution of TFEB-WT and TFEB-S3A/R4A mutant upon incubation with DMSO (vehicle) or 250 nM Torin-1 for 1 h. Cells were fixed, permeabilized with 0.2% Triton X-100, and stained with antibodies against FLAG (used to detect TFEB).",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(E) ARPE-19 cells expressing either TFEB-S211A or TFEB-S211A-Δ30 were double stained with antibodies against TFEB and Lamp1. Regions within the dotted boxes are magnified in the insets.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(A) ARPE-19 cells coexpressing active RagB/D heterodimer and the indicated TFEB plasmids were fixed, permeabilized with 0.2% saponin, and stained with antibodies against GST (used to detect Rag proteins). Regions within the dotted boxes are magnified in the insets. Bars, 10 µm.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(B) ARPE-19 cells were cotransfected with active RagB/D heterodimers and the indicated TFEB constructs. After 18 h, cell lysates were immunoprecipitated with the anti-HA antibody (used to immunoprecipitate Rag proteins) and immunoblotted with antibodies against GFP and GST (used to detect TFEB-GFP and Rag proteins, respectively). The white line indicates that intervening lanes have been spliced out.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(C) Immunofluorescence confocal microscopy showing the subcellular distribution of TFEB-(1-30)-GFP in ARPE-19 cells coexpressing active RagB/D heterodimers (antibodies against GST were used to detect Rags). Bar, 4 µm.",
    "ncbi_link": "TFEB: 7942"
  },
  {
    "caption": "(D) Relative RT-PCR analysis of the mRNA expression of autophagy (ATG9B and UVRAG) and lysosomal (MCOLN1) genes in ARPE-19 cells infected with the indicated adenovirus for 48 h. The values are expressed as a ratio to RNA from cells infected with control adenovirus (Ad.-Null). Values are means ± SD of two independent experiments. ***, P < 0.001; **, P < 0.01.",
    "ncbi_link": "ATG9B: 285973
MCOLN1: 57192
UVRAG: 7405"
  },
  {
    "caption": "(G) ARPE-19 cells expressing active (RagBGTP/RagDGDP) or inactive (RagBGDP/RagDGTP) Rag heterodimers were immunoprecipitated with the anti-FLAG antibody and immunoblotted with antibodies against FLAG and GST (used to detect MITF and Rag proteins, respectively).",
    "ncbi_link": "RagB: 10325
RagD: 58528"
  },
  {
    "caption": "(H) HEK-293T cells expressing active (RagBGTP/RagDGDP) or inactive (RagBGDP/RagDGTP) Rag heterodimers were pulled down using glutathione-Sepharose beads and immunoblotted with antibodies against GST and MITF (used to detect Rag proteins and endogenous MITF, respectively). IP, immunoprecipitation.",
    "ncbi_link": "RagB: 10325
RagD: 58528"
  },
  {
    "caption": "(G) Left, Ki67 staining  of PDI+/+ and PDI-/- hESCs. Scale bar, 25 µm. Right, statistical analysis of Ki67-positive cells. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(C) Immunostaining  of PDI  and calreticulin  (CRT) in PDI+/+ and PDI-/- hMSCs, CRT  was used as ER  marker. Scale bar, 25 µm.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(D) Western blotting  analysis of PDI  family members expression  in PDI+/+ and PDI-/- hMSCs  at early-passage  (P3) and   late-passage   (P8). GAPDH  was used as the loading control.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(G) Left, Ki67 staining  of PDI+/+ and PDI-/- hMSCs  at P8. Scale bar, 20 µm. Right, statistical analysis of Ki67-positive cells. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(H) Left, SA-β-gal staining  of PDI+/+ and PDI-/- hMSCs  at P8. Scale bar, 200 µm. Right, statistical analysis of SA-β-gal-positive cells. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(K) Left, western blotting showing the P16 expression  in PDI+/+ and PDI-/- hMSCs  at P8. GAPDH  was used as the loading control. Right, statistical analysis of relative P16 protein expression  levels. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(M) Left, Immunostaining  of 53BP1  and γH2AX  in PDI+/+ and PDI-/- hMSCs  at P8. White arrowheads indicate 53BP1  and γH2AX  double positive cells. Right, statistical analysis of 53BP1  and γH2AX  double positive cells. Scale bar, 10 µm. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(P) Left, Ki67 staining  of PDI-/- hMSCs  transduced with lentiviruses  expressing Luc  or PDI. Scale bar, 10 µm. Right, statistical analysis of Ki67-positive cells. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "Luc: 
PDI: 5034"
  },
  {
    "caption": "(Q) Left, SA-β-gal staining  of PDI-/- hMSCs  transduced with lentiviruses  expressing Luc  or PDI. Scale bar, 200 µm. Right, statistical analysis of SA-β-gal-positive cells. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "Luc: 
PDI: 5034"
  },
  {
    "caption": "(A) Oxidative  folding of Myc-tagged J-Chain (JcM). PDI+/+ and PDI-/- hMSCs  were transfected with JcM  for 48 hr, then were pulsed with DTT  and chased at indicated time  after DTT  removal. The lysates were analyzed using non-reducing SDS-15% PAGE and α-Myc western blotting. The mobility of reduced JcM  monomers (Red), oxidized  monomers (Oxi), homodimers (Dim), and high-molecular-weight (HMW) species are indicated.",
    "ncbi_link": "JcM: 3512
PDI: 5034"
  },
  {
    "caption": "(D) Time-dependent changes of H2O2  levels in the ER  of PDI+/+ and PDI-/- hMSCs  at P8. Left, the fluorescence intensity ratio of HyPer-ER  at 535 nm with excitation at 488 and 405 nm were firstly monitored at resting state for 5 min, followed by addition of 0.5 mM DTT  (yellow bar) for another 15 min. Right, statistical analysis of the fluorescence intensity ratio at 488/405 nm excitation of HyPer-ER  probe at 15 min post DTT  addition. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(E) Analysis of the H2O2  levels in PDI+/+ and PDI-/- hMSCs at P8 using Amplex Red assays. n = 3 biological repeats. (F) Analysis of the cellular total ROS  levels in PDI+/+ and PDI-/- hMSCs  at P8 using H2DCFDA  probe. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(M) Confocal  imaging of PDI+/+ and PDI-/- hMSCs  expressing Hyper7-nucleus  at steady state and upon addition of 2 mM DTT. The fluorescence intensity ratio at 488/405 nm obtained from individual cells was calculated at indicated times  with a representative false color image. Scale bar, 10 μm.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(C, D) Density plot showing that upregulated (C) or downregulated (D) genes in the LP hMSCs  (PDI+/+, LP   vs. PDI+/+, EP) that were restored after PDI  deletion (PDI-/-, LP   vs. PDI+/+, LP). Comparisons were performed with two-sided Wilcoxon signed-rank test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(K) Conjoint analysis showing the secretion levels of PDI  and those in (I) and various SASPs from multiple senescence inducers and in plasma  proteome from 3,087 healthy individuals RS, replicative senescence (PDI+/+, LP   vs. PDI+/+, EP). ATV, atazanavir  treatment; RAS, inducible RAS  overexpression; IR, X-irradiation. The color keys that change from dark blue to dark purple represent the fold change of gene and protein, change from white to red represent the change in protein levels per unit increase in the covariate in plasma  proteomic.",
    "ncbi_link": "RAS: 
PDI: 5034"
  },
  {
    "caption": "(A) qPCR  analysis of SERPINE1  expression in PDI+/+ and PDI-/- hMSCs  at EP   and LP. n = 3 independent experiments. Data information: In (A, data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034
SERPINE1: 5054"
  },
  {
    "caption": "(B) Western blotting analysis of SERPINE1  protein in PDI+/+ and PDI-/- hMSCs  at EP   and LP. GAPDH  was used as the loading control of cell lysates. Ponceau  was used as the loading control of conditional medium.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(F) Left, Ki67 staining  in PDI-/- hMSCs  transduced with sgNTC or  SERPINE1-targeting activation sgRNAs. Scale bar, 20 μm. Right, statistical analysis of Ki67-positive cells. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034
SERPINE1: 5054"
  },
  {
    "caption": "(G) Left, SA-β-gal staining  in PDI-/- hMSCs  transduced with sgNTC or SERPINE1-targeting activation sgRNAs. Scale bar, 200 μm. Right, statistical analysis of SA-β-gal-positive cells. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034
SERPINE1: 5054"
  },
  {
    "caption": "(H) qPCR  analysis of the SERPINE1  mRNA expression in PDI+/+ and PDI-/- hMSCs  treated with the indicated concentration H2O2  for 4 days. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034
SERPINE1: 5054"
  },
  {
    "caption": "(J) H2O2  levels in PDI-/- hMSCs  transduced with lentiviruses  expressing Luc  or PDI   were determined by the fluorescence ratio of HyPer-ER  at 488/405 nm excitation after the addition of 0.5 mM DTT  for 15 min. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "Luc: 
PDI: 5034"
  },
  {
    "caption": "(K) H2O2  levels in PDI-/- hMSCs  transduced with lentiviruses  expressing Luc  or PDI   were determined by the fluorescence ratio of HyPer7-nucleus  at 500/400 nm excitation after the addition of 2 mM DTT  for 20 min. n = 3 independent experiments. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "Luc: 
PDI: 5034"
  },
  {
    "caption": "(A) Western blotting of PDI expression  in replicative senescent (RS) hMSCs, Hutchinson-Gilford Progeria Syndrome (HGPS) hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. GAPDH  was used as the loading control.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(B) Single clonal formation assay  in RS hMSCs, HGPS hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. n = 3 biological repeats. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "(C) SA-β-gal staining  in RS hMSCs, HGPS hMSCs, WS hMSCs  and human  primary hMSCs  from an old individual transduced with sgNTC or PDI-targeting sgRNA. n = 3 biological repeats. Scale bar, 200 µm. Data information: data are presented as mean ± SEM, two-tailed Student's t-test.",
    "ncbi_link": "PDI: 5034"
  },
  {
    "caption": "C. Flag-tagged WT and mutant WDTC1proteins were transiently expressed in 293T cells. Flag-WDTC1 complexes were immunoprecipitated with anti-FLAG and their associated proteins were detected by immunoblotting as indicated; EV, empty vector control.",
    "ncbi_link": "WDTC1: 23038"
  },
  {
    "caption": "E. 293T cells were transfected with HA-ubiquitin along with various combinations of plasmid and siRNA as indicated. Transfected cells were lysed under denaturing conditions to obtain whole cell extracts (WCE) and immunoprecipitated with anti-FLAG. WDTC1 ubiquitylation was evaluated by immunoblotting as indicated.",
    "ncbi_link": "WDTC1: 23038"
  },
  {
    "caption": "F. 293T cells transiently expressing Flag-WDTC1 were transfected with scramble (scrm) siRNA or siRNAs against DDB1, CUL4A and CUL4B. Flag-WDTC1 levels and knockdown efficiency were assessed by immunoblotting as indicated.",
    "ncbi_link": "DDB1: 1642"
  },
  {
    "caption": "A. Schematic of WDTC1 knockdown-rescue lentiviral vector (top). 3T3-L1preadipocytes were lentivirally transduced to generate stable cells expressing a non-specific (NS) shRNA control, shWDTC1 targeting endogenous Wdtc1mRNA, or cells simultaneously expressing shWDTC1 and shRNA-resistant WDTC1; bottom, confirmation of knockdown and WDTC1 ectopic expression.",
    "ncbi_link": "WDTC1: 23038
Wdtc1: Q8N5D0///230796"
  },
  {
    "caption": "B. Chromatin enriched nuclear extracts from 293T cells cotransfected with Flag-WDTC1 and HA tagged core histones were immunoprecipitated (IP) with anti-FLAG and immunoblotted (IB) as indicated. The probable H2AK119ub1 band detected in the nuclear extract is indicated by an asterisk.",
    "ncbi_link": "WDTC1: 23038"
  },
  {
    "caption": "D. Affinity purified Flag-WDTC1 wildtype and mutant ΔH complexes from 293T cells were the source of E3 ligase in in vitro ubiquitylation assays. Copurification of CRL4 E3 ligase proteins was confirmed by immunoblotting and Coomassie Blue staining (left panel). In vitro ubiquitylation assays of recombinant H2A were performed in the presence of indicated proteins. Reaction products were resolved by SDS-PAGE, and ubiquitylatedH2A was detected by anti-H2AK119ub1 (right panel).",
    "ncbi_link": "H2A: 
WDTC1: 23038"
  },
  {
    "caption": "A Representative photographs of fly eyes expressing (CGG)90-EGFP under a GMR-GAL4 driver, with various belle disruptions.",
    "ncbi_link": "EGFP: 
belle: 45826
GAL4: 855828"
  },
  {
    "caption": "B Quantitation of GMR-GAL4, (CGG)90-EGFP eye phenotypes with belle disruptions (Mann-Whitney U test with Bonferonni corrections for multiple comparisons; n=35-77/genotype). Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All data in all panels are presented as mean ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
belle: 45826
GAL4: 855828"
  },
  {
    "caption": "Longevity assays of (CGG)90-EGFP; Tub5-GS (Log-rank Mantel-Cox test with Bonferroni corrections for multiple comparisons; n=110-219/genotype) flies with belle knockdown. Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All data in all panels are presented as mean ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
Tub5: 
belle: 45826"
  },
  {
    "caption": "Longevity assays of (CGG)90-EGFP; ElaV-GS (n=147-299/genotype) flies with belle knockdown. Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All data in all panels are presented as mean ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
belle: 45826
ElaV: 31000"
  },
  {
    "caption": "G Abundance of (CGG)90-EGFP mRNA normalized to RPL32 mRNA, following belle knockdown, determined by qRT-PCR (n=8/genotype).",
    "ncbi_link": "EGFP: 
belle: 45826
RPL32: 43573"
  },
  {
    "caption": "H Western blot of AUG-driven EGFP in EGFP; Tub5-GS flies with and without belle knockdown.",
    "ncbi_link": "EGFP: 
Tub5: 
belle: 45826"
  },
  {
    "caption": "A Dose-response curves showing the effects of two independent anti-DDX3X siRNAs on the expression of AUG-NL-3xF (top) and (CGG)100 +1 NL-3xF (bottom) reporters. Plasmid-based reporters were transfected into HeLa cells 24 hours after knockdown, and reporter expression was quantified by luminescence. Nanoluciferase (NL) luminescence has been normalized to luminescence from firefly luciferase (FF), which was co-transfected, in order to control for transfection variability. Asterisks refer to comparisons between anti-DDX3X siRNAs and siRNAs against EGFP (siEGFP; two-way ANOVA with Dunnett's multiple comparisons test; n=12/condition). Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
FF: 
luciferase: 
Nanoluciferase: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "(CGG)n +1 NL-3xF expression (normalized to FF) with and without DDX3X knockdown across a range of CGG repeat sizes. Black asterisks refer to comparisons between siDDX3X- and siEGFP-treated cells; orange asterisks refer to comparisons between siDDX3X-treated cells expressing AUG-NL-3xF and those expressing a different reporter (two-way ANOVA with Tukey's multiple comparisons test; n=17-30/condition). Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
FF: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "(CGG)n +2 NL-3xF expression (normalized to FF) with and without DDX3X knockdown across a range of CGG repeat sizes. Black asterisks refer to comparisons between siDDX3X- and siEGFP-treated cells; orange asterisks refer to comparisons between siDDX3X-treated cells expressing AUG-NL-3xF and those expressing a different reporter (two-way ANOVA with Tukey's multiple comparisons test; n=17-30/condition). Data Information: For all panels, * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
FF: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "Western blots of FMRpolyG-NL-3xF products with and without DDX3X knockdown across a range of repeat sizes.",
    "ncbi_link": "DDX3X: 1654"
  },
  {
    "caption": "Western blots of FMRpolyA-NL-3xF products with and without DDX3X knockdown across a range of repeat sizes.",
    "ncbi_link": "NL: 
DDX3X: 1654"
  },
  {
    "caption": "A Expression of in vitro transcribed AUG, +1 (CGG)100, and +2 (CGG)100 NL-3xF RNAs following DDX3X knockdown in HeLa cells, expressed as NL luminescence normalized to FF luminescence. (Student's t test with Bonferroni corrections for multiple comparisons; n=21/condition). Data Information: For all panels, ns=non-significant, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD, unless indicated otherwise (compiled from ≥3 replicates).",
    "ncbi_link": "FF: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "B Abundance of reporter mRNAs following DDX3X knockdown and plasmid-reporter transfection, determined by qRT-PCR. (n=7/condition.) This panel depicts data as means ± SEM.",
    "ncbi_link": "DDX3X: 1654"
  },
  {
    "caption": "C Expression of AUG-NL-3xF and +1 (CGG)100 NL-3xF in in vitro translation extracts, collected from HeLa cells treated with siRNAs against EGFP or DDX3X (two-way ANOVA with Tukey's multiple comparisons test; n=4/condition). Data Information: For all panels, ns=non-significant, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD, unless indicated otherwise (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "D Enrichment of HSPA1A and +1 (CGG)100 NL-3xF mRNA following anti-DDX3X RIP, relative to incubation with isotype control IgG. MALAT RNA, in contrast, is not enriched (Student's t test, n=3).",
    "ncbi_link": "NL: 
DDX3X: 1654
HSPA1A: 3303
MALAT: 378938"
  },
  {
    "caption": "E Expression of +1 and +2 (CGG)100 NL-3xF plasmid reporters with and without an AUG inserted 5' to the CGG repeat, with and without DDX3X knockdown. Black asterisks refer to comparisons between siDDX3X- and siEGFP-treated cells; orange asterisks refer to comparisons between siDDX3X-treated cells expressing either +1 or +2 (CGG)100 NL-3xF and those expressing the respective AUG-driven variant (two-way ANOVA with Tukey's multiple comparisons test; n=11-12/condition). Data Information: For all panels, ns=non-significant, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD, unless indicated otherwise (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "F Expression of NL-3xF plasmids with initiator AUG codons mutated to near-AUG codons, with and without DDX3X knockdown (two-way ANOVA with Dunnett's multiple comparisons test; n=18-24/condition). Black asterisks refer to comparisons between siEGFP-treated and siDDX3X-treated cells; orange asterisks refer to comparisons between siDDX3X-treated cells expressing AUG-NL-3xF and those expressing a different reporter; white asterisks refer to comparisons between siDDX3X-treated cells expressing +1 (CGG)100 NL-3xF and those expressing a different reporter. Data Information: For all panels, ns=non-significant, *** P≤0.001, **** P≤0.0001 for the specified statistical test. All panels depict data as means ± SD, unless indicated otherwise (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
NL: 
DDX3X: 1654"
  },
  {
    "caption": "G Expression of in vitro transcribed near-AUG reporter RNAs in in vitro translation extracts, collected from HeLa cells treated with siRNAs against EGFP or DDX3X. (n=4/group).",
    "ncbi_link": "EGFP: 
DDX3X: 1654"
  },
  {
    "caption": "A Representative photographs of GMR-GAL4; (CGG)90-EGFP fly eyes expressing manipulations of eIF4B and eIF4H. (B) Quantitation of GMR-GAL4, (CGG)90-EGFP eye phenotypes with eIF4B/H manipulations (Mann-Whitney U test with Bonferroni corrections for multiple comparisons; n=26-55/genotype). Data Information: For all panels, ns=non-significant, * P≤0.05, ** P≤0.01, **** P≤0.0001 for the specified statistical test. All panels present data as means ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
eIF4B: 3355041
eIF4H: 49809
GAL4: 855828"
  },
  {
    "caption": "C, D Expression of plasmid-based AUG-NL and +1 (CGG)100 NL-3xF reporters (C), or co-transfected AUG-FF reporters (D), following knockdown of EIF4B or EIF4H. Black asterisks refer to comparisons between siEGFP- and siEIF4B/H-treated cells; pink and blue asterisks refer to comparisons between siEIF4B- (pink) or siEIF4H- (blue) treated cells expressing AUG-NL-3xF and those expressing +1 (CGG)100 (two-way ANOVA with Tukey's multiple comparisons test, n=9/condition).",
    "ncbi_link": "EGFP: 
FF: 
NL: 
EIF4B: 1975
EIF4H: 7458"
  },
  {
    "caption": "E Expression of plasmid-based AUG-NL-3xF and (CGG)100 +1 NL-3xF reporters with and without over-expression of EIF4B, EIF4H, or both (two-way ANOVA with Dunnett's multiple comparisons test; n=20/condition). Asterisks refer to comparisons between cells over-expressing either EGFP or EIF4B, EIF4H, or EIF4B and EIF4H and expressing the same reporter. Data Information: For all panels, ns=non-significant, * P≤0.05, ** P≤0.01, **** P≤0.0001 for the specified statistical test. All panels present data as means ± SD (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: 
NL: 
EIF4B: 1975
EIF4H: 7458"
  },
  {
    "caption": "A Expression of plasmid-based NL-3xF reporters in HEK293 cells with and without over-expression of EIF1 (two-way ANOVA with Sidak's multiple comparisons test; n=9-12/condition). Black asterisks refer to comparisons between Empty Vector-transfected and EIF1-transfected cells; green asterisks refer to comparisons between EIF1-transfected cells expressing AUG-NL-3xF and those expressing a different reporter. For all panels, *** P≤0.001, **** P≤0.0001 for the specified statistical test. Bars represent mean ± SEM (compiled from ≥3 replicates).",
    "ncbi_link": "NL: 
EIF1: 10209"
  },
  {
    "caption": "B Expression of plasmid-based NL-3xF reporters in HEK293 cells with and without over-expression of EIF5 (two-way ANOVA with Sidak's multiple comparisons test; n=9-12/condition). Black asterisks refer to comparisons between Empty Vector-transfected and EIF5-transfected cells; pink asterisks refer to comparisons between EIF5-transfected cells expressing AUG-NL-3xF and those expressing a different reporter. For all panels, *** P≤0.001, **** P≤0.0001 for the specified statistical test. Bars represent mean ± SEM (compiled from ≥3 replicates).",
    "ncbi_link": "NL: 
EIF5: 1983"
  },
  {
    "caption": "C Expression of EGFP in primary rat neurons transfected with (CGG)100 (+1) EGFP and either anti-DDX3X LNAs or a control (one-way ANOVA with Tukey's multiple comparisons test; n=2408-5689 cells/condition). All graphs depict pooled data, normalized first within the replicate. Data Information: For all panels, **** P≤0.0001 for the specified statistical test (compiled from ≥3 replicates).",
    "ncbi_link": "EGFP: "
  },
  {
    "caption": "D HCT116, Lovo and RKO cells were transfected with control or p53 siRNAs. 48 h after transfection, total protein was then analyzed by western blot analysis. E HCT116, Lovo and RKO cells were transfected with empty vector and p53 plasmid. 48 h after transfection, total protein was then analyzed by western blot analysis.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "F Representative immunofluorescence staining of the p53 (green) and METTL14 (red) proteins in p53-WT HCT116, Lovo and RKO cells and p53-MT HT29 (p53R273H), SW480 (p53R273H/P309S), SW620 (p53R273H) and SW1116 (p53A159D) cells. Nuclei were stained with DAPI (blue). Scale bars = 10 μm. The relative mean fluorescence density was analyzed by ImageJ.",
    "ncbi_link": "p53: 7157
p53: 22059"
  },
  {
    "caption": "I Western blot analysis of METTL14 levels after transfection with empty vector, wild-type or mutant p53 plasmids in HCT116 (p53-/-) cells.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "J Representative IHC images, and statistical analysis of immunoreactive score (IRS) of METTL14 expression in p53-WT (n = 63) and p53-MT (n = 41) CRC samples. The horizontal lines represent the median; the bottom and top of the boxes represent the 25% and 75% percentiles, respectively; and the vertical bars represent the range of the data. The insets show enlarged images of indicated p53-WT and p53-MT CRC tissues, respectively. Scale bars = 20 μm and 2 μm (inset).",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "K ChIP assay verified the potential p53 binding site in the METTL14 promoter region in HCT116 and Lovo cell lines. Input fractions and IgG were used as controls.",
    "ncbi_link": "METTL14: 57721"
  },
  {
    "caption": "A Colony formation assay of p53-WT (HCT116, Lovo and RKO) and p53-MT (HT29, SW620, SW1116 and SW480) cells stably infected with shNC or shMETTL14. Data are presented as mean ± SD (biological replicates, n = 3; *P < 0.05, **P < 0.01, ns = no significance).",
    "ncbi_link": "METTL14: 210529
p53: 7157
p53: 22059"
  },
  {
    "caption": "B, C Representative images and analysis of tumors in nude mice bearing stably transfected shNC or shMETTL14 p53-WT (HCT116 and Lovo) and p53-MT (HT29 and SW620) cells. Data are presented as mean ± SD (biological replicates, n = 7, ns = no significance).",
    "ncbi_link": "METTL14: 210529
p53: 7157
p53: 22059"
  },
  {
    "caption": "G Comparison of colorectum length between METTL14WT (n = 14, n = 24) and METTL14ΔIEC (n = 13, n = 21) mice from AOM/DSS-induced and AOM-induced CRC models, respectively. Data are expressed as mean ± SD.",
    "ncbi_link": "METTL14: 210529"
  },
  {
    "caption": "I Representative HE staining images of colorectum in METTL14WT (n = 14, n = 24) and METTL14ΔIEC (n = 13, n = 21) mice from AOM/DSS-induced and AOM-induced CRC models. Lower panels show enlarged images of indicated normal or CRC tissues. Scale bars = 2 mm (upper) and 40 μm (lower). Black dashed line refers to the border of tumor (T) and normal (N) tissues. Tumors are classified as adenomas with low to focal high-grade dysplasia. The percentages of mice with dysplasia are shown (right).",
    "ncbi_link": "METTL14: 210529"
  },
  {
    "caption": "C Lactate production, ATP level, glucose uptake and pyruvate level in stably transfected Lv-vector and Lv-METTL14 or shNC and shMETTL14 HCT116 (p53-WT) cells. Data are presented as mean ± SD (biological replicates, n = 3; **P < 0.01).",
    "ncbi_link": "METTL14: 57721
p53: 7157"
  },
  {
    "caption": "H Western blot analysis of METTL14, SLC2A3 and PGAM1 protein levels of intestinal epithelial cells from AOM/DSS-induced Mettl14WT (n = 4) and Mettl14ΔIEC (n = 4) and mice.",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "I Representative IHC staining images and quantitative analysis of SLC2A3 and PGAM1 in tumor tissues and non-tumor tissues from AOM/DSS-induced Mettl14ΔIEC and Mettl14WT mice CRC models. The insets show enlarged images of tumor tissues and non-tumor tissues, respectively. Scale bars = 40 μm and 4 μm (inset). Data are presented as mean ± SD (biological replicates, n = 6; **P < 0.01, ***P < 0.001).",
    "ncbi_link": "Mettl14: 210529"
  },
  {
    "caption": "E Western blot analysis of SLC2A3 and PGAM1 protein levels in HCT116 and Lovo (p53-WT) cells transfected with control or miRNA mimics.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "F Representative IF staining and quantitative analysis of the SLC2A3 (green) and PGAM1 (green) proteins in HCT116 (p53-WT) cells transfected with control or miRNA mimics. Nuclei were stained with DAPI (blue). Scale bars = 20 μm. Data are presented as mean ± SD (biological replicates, n = 4; **P < 0.01). G Representative IF staining and quantitative analysis of the SLC2A3 (green) and PGAM1 (green) proteins in HT29 (p53-MT) cells transfected with control or miRNA mimics. Nuclei were stained with DAPI (blue). Scalebars = 20 μm. Data are presented as mean ± SD (biological replicates, n = 4; ns = no significance).",
    "ncbi_link": "p53: 7157
p53: 22059"
  },
  {
    "caption": "J qRT-PCR analysis of the pri-miR-6769b and pri-miR-499a levels in stably transfected Lv-vector and Lv-METTL14 HCT116 cells with control, YTHDF1-3, YTHDC1-2 or IGF2BP1-3 siRNAs. Data are presented as mean ± SD (biological replicates, n = 3; **P < 0.01). The dotted line represents basal mRNA expression of pri-miR-6769b and pri-miR-499a in HCT116 cells, acting as a control.",
    "ncbi_link": "IGF2BP1: 10642
METTL14: 57721
pri-miR-499a: 574501
pri-miR-6769b: 102466202
YTHDC1: 91746
YTHDF1: 54915"
  },
  {
    "caption": "N Representative images of tumors and analysis in nude mice intervened with control, miR-6769b-3p or miR-499a-3p expression p53-WT (HCT116 and Lovo) cells. Data are presented as mean ± SD (biological replicates, n = 7). O Representative images of tumors and analysis in nude mice intervened with control, miR-6769b-3p or miR-499a-3p expression p53-MT (HT29 and SW620) cells. Data are presented as mean ± SD (biological replicates, n = 7, ns, no significance).",
    "ncbi_link": "miR-499a-3p: 574501
miR-6769b-3p: 102466202
miR-6769b-3p: 102466799
p53: 7157
p53: 22059"
  },
  {
    "caption": "A Glucose uptake, Lactate, ATP, pyruvate levels were determined in HCT116 (p53-WT) cells treated with control, miR-6769b-3p mimics or inhibitor for 48h. B Glucose uptake, Lactate, ATP, pyruvate levels were determined in HCT116 (p53-WT) cells treated with control, miR-499a-3p mimics or inhibitor for 48h.",
    "ncbi_link": "miR-499a-3p: 574501
miR-6769b-3p: 102466202
p53: 7157"
  },
  {
    "caption": "E Glucose uptake, Lactate, ATP and pyruvate levels were determined in stably transfected Lv-vector and Lv-METTL14 HCT116 (p53-WT) cells treated with control or mixture inhibitors for 48h. Western blot analysis of the corresponding METTL14, SLC2A3 and PGAM1 protein levels in indicated treatment. F Glucose uptake, Lactate, ATP and pyruvate levels were determined in stably transfected Lv-vector and Lv-METTL14 HCT116 (p53-WT) cells treated with control or mixture mimics for 48h. Western blot analysis of the corresponding METTL14, SLC2A3 and PGAM1 protein levels in indicated treatment.",
    "ncbi_link": "METTL14: 57721
p53: 7157"
  },
  {
    "caption": "I, J Representative images and analysis of tumors in nude mice generated by stably transfected shNC and shMETTL14 or miR-6769b-3p and miR-499a-3p overexpressing HCT116 (p53-WT) cells with or without METTL14 knockdown. Data are presented as mean ± SD (biological replicates, n = 7, ***P < 0.001).",
    "ncbi_link": "METTL14: 57721
miR-499a-3p: 574501
miR-6769b-3p: 102466202
p53: 7157"
  },
  {
    "caption": "A Representative IHC and ISH staining images and corresponding quantitative analysis of miR-6769b-3p/SLC2A3 IRS and miR-499a-3p/PGAM1 IRS in p53-WT (n = 63) and p53-MT (n = 41) samples from Cohort 3. The insets show enlarged images of indicated p53-WT and p53-MT CRC tissues, respectively. Scale bars = 200 μm and 20 μm (inset). The horizontal lines represent the median; the bottom and top of the boxes represent the 25% and 75% percentiles, respectively; and the vertical bars represent the range of the data.",
    "ncbi_link": "miR-499a-3p: 574501
miR-6769b-3p: 102466202
p53: 7157"
  },
  {
    "caption": "B Representative IHC and ISH images of METTL14, SLC2A3, PGAM1, miR-6769b-3p and miR-499a-3p in CRC tissues with higher or lower METTL14 expression in p53-WT (n = 63) samples from Cohort 3. Right panels show enlarged images of indicated p53-WT CRC tissues. Scale bars = 200 μm (left) and 20 μm (right).",
    "ncbi_link": "miR-499a-3p: 574501
miR-6769b-3p: 102466202
p53: 7157"
  },
  {
    "caption": "F Kaplan-Meier survival curves of OS in CRC patients with wild type p53 (n = 63) and mutant p53 (n = 41) from Cohort 3 database based on expression levels of METTL14.",
    "ncbi_link": "p53: 7157"
  },
  {
    "caption": "(C-G)   ssDNA repair efficiency of the indicated TS mutants as determined from the maximal and final percentages of cells with Rad52 foci during the time course (right panels). Cells were synchronized in G1 and released into  S phase in the presence of 0.033% MMS for 1 hour (60+), treated with 2.5% sodium thiosulfate to inactivate the MMS, washed and released into fresh medium for different times. They were also released into medium without MMS for 1 hour to control the formation of spontaneous Rad52-YFP foci (60-). The percentage of cells with foci at each point was normalized to the highest value of the wild type, taken as 100 (left panels). Cell cycle progression  was determined by cell sorting. The mean and SEM of 3 (wild type, rad18∆, mms2∆, rad51∆, rad57∆, rad54∆), 4 (pol30-K164R) and 5 (rad5∆) independent experiments are shown. Statistically significant differences according to an unpaired two-tailed Student's t-test are shown, where three asterisks represent p-values <0.001.",
    "ncbi_link": "mms2: 852793
pol30: 852385
rad18: 850430
rad5: 850719
rad51: 856831
rad54: 852713
rad57: 851567"
  },
  {
    "caption": "(C-E)  ssDNA repair efficiency  of the indicated TLS mutants as determined from the maximal and final percentages of cells with  Rad52 foci during the time course (D and E, right panel). Cells were synchronized in G1 and released into  S phase in the presence of 0.033% MMS for 1 hour, treated with 2.5% sodium thiosulfate to inactivate the  MMS, washed and released into fresh medium for different times. The percentage of cells with foci at each point was normalized to the highest value of the wild type, taken as 100 (C and E, left panel). Data information: The mean and SEM of and 3-12 12 (wild type), 6 (rev1∆,  rev3∆, rad30∆, rev1∆ rad30∆, rev3∆ rad30∆), and 3 (rev1∆  rev3∆ and rev1∆ rev3∆ rad30∆) independent experiments are shown. Statistically significant differences according to an unpaired two-tailed Student's t-test are shown, where one, two and three asterisks represent p-values <0.05, <0.01 and <0.001, respectively.",
    "ncbi_link": "rad30: 852028
rev1: 854527
rev3: 855936"
  },
  {
    "caption": "(C-D)  ssDNA repair efficiency  of the rad5∆ and  rev1∆ mutants as determined from the maximal and final percentages of cells with Rad54  foci during the time course (right panels). Cells were synchronized in G1  and released into S phase  in the presence of 0.033% MMS  for 1 hour, treated with 2.5% sodium thiosulfate to inactivate the MMS, washed and released into fresh medium for different times. The percentage of cells with foci at each point was normalized to the highest value of the wild type, taken as 100 (left panels). Data information: The mean and SEM of independent experiments are shown. Statistically significant differences according to an unpaired two-tailed Student's t-test are shown, where one, two and three asterisks represent p-values <0.05, <0.01 and <0.001, respectively.",
    "ncbi_link": "rad5: 850719
rev1: 854527"
  },
  {
    "caption": "(F)   ssDNA repair efficiency  of the indicated mutants as determined by ChIP  against  Rfa1-YFP at the ARS305 replication origin. Cells were synchronized in G1 and released into S phase in the presence of 0.033% MMS for 1 hour, treated with 2.5% sodium thiosulfate to inactivate the MMS, washed and released into fresh medium. The amount of  Rfa1 at ssDNA was determined at 1 and 7 hours after MMS  release. RPA  enrichment was calculated as the ratio between  immunoprecipitate  and input values. All values were normalized to the wild type at 7 hours, taken as 1. Data information: The mean and SEM of 3 independent experiments are shown. Asterisks indicate statistically significant differences according to an unpaired two-tailed Student's t-test. One, two and three asterisks represent p-values <0.05, <0.01 and <0.001, respectively. In (F) all values were significant relative to the untagged controls (not shown for clarity).",
    "ncbi_link": "ARS305: "
  },
  {
    "caption": "Effect of the lack of HR factors in spontaneous and  MMS-induced mutagenesis. The frequency of spontaneous and MMS-induced forward  mutagenesis at the CAN1 locus was determined in mid-log phase cell cultures before (spontaneous mutagenesis) and after treatment with 0.01% MMS for 4 hours (DNA damage-induced). Thus, the frequency of DNA damage-induced mutagenesis includes the mutants that arose spontaneously before MMS addition. The frequency of mutagenesis  was determined at 0.01% MMS because at higher MMS  concentrations the loss of  viability of the rad mutants did not allow us to select for canavanine-resistant cells. Survival  (%) after 4 hours in  MMS  relative to the wild type (taken as 100) is shown below the genotypes. The mean and SEM of 6 (wild type), 9 (rad54∆) and 3 (rest) independent fluctuation tests are shown. Asterisks indicate statistically significant differences according to an unpaired two-tailed Student's t-test (one, two and three asterisks represent p-values <0.05, <0.01 and <0.001, respectively). Only the statistical analysis of the effect of  rad52∆, rad57∆ and rad51∆ on rad54∆-mediated  mutagenesis  is included for clarity. All mutants displayed statistically significant differences with the wild type and not with each other in the absence of MMS.",
    "ncbi_link": "CAN1: 856646
rad51: 856831
rad52: 854976
rad54: 852713
rad57: 851567"
  },
  {
    "caption": "(A) Effect of the  rad54∆ and rad52∆ mutations in spontaneous and UV-induced uSCE. The frequency of spontaneous and UV-induced recombinants was determined by irradiating or not cells plated onto solid medium after the corresponding dilutions (SMM and SMM without histidine  to calculate total and recombinant cells, respectively). The mean and SEM of 3-5 independent fluctuation tests are shown. Asterisks indicate statistically significant differences according to an unpaired two-tailed Student's t-test. Two and three asterisks represent p-values <0.01 and <0.001, respectively.",
    "ncbi_link": "rad52: 854976
rad54: 852713"
  },
  {
    "caption": "(C-F) Rad6 binding  to DNA depends on Rad18, Rad52  (C), Rad51 (D), Rad57  (E) but not  Rad54 (F) as determined by ChEC analyses of asynchronous cell cultures without or with 0.05% MMS for 2 hours. Data information: DNA gel  electrophoresis, DNA content (cell sorting) and quantification of DNA digestion profiles  are shown. The experiments were repeated twice with similar results.",
    "ncbi_link": "Rad18: 850430
Rad51: 856831
Rad52: 854976
Rad54: 852713
Rad57: 851567"
  },
  {
    "caption": "(A-D) Effect of  rad52∆,  rad51∆ (A), rad57∆ (B) and rad54∆ (C) on PCNA ubiquitylation in cells synchronized in G1  and released into fresh medium in the presence of 0.025% MMS.  Cell cycle progression was followed by cell sorting  analysis and  western blot  against  Clb2. Pgk1 was used as loading control. The amounts of mono- and polyubiquitylated PCNA were normalized to the total amount of PCNA. For each time point, rad mutant values were relativized to those of the wild type, taken as 1. The mean and SEM of 3 independent experiments are shown (D). An asterisk indicates a mean significantly different than 1, according to a One-sample t-test.",
    "ncbi_link": "rad51: 856831
rad52: 854976
rad54: 852713
rad57: 851567"
  },
  {
    "caption": "A The first 400 nt of all 3'UTRs represented in the UPF1 RIP-Seq dataset were analyzed for the occurrence of motifs corresponding to the indicated RNA-binding proteins. Transcripts were divided into groups based on the number of motifs present (0, 1, more than 1), indicated by the gradient triangle. The dotted line indicates the mean RIP-Seq efficiency for all transcripts used in the analysis. Mean and SD are plotted for all groups.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "B CDF plot of relative abundance of transcripts with 3'UTRs > 1000 nt in K562 cells under conditions of UPF1 or non-targeting shRNA, for transcripts with hnRNP L eCLIP peaks in the indicated intervals Each trace represents a category of CLIP peak locations. For mRNAs with peaks > 400 nt from the TC or with peaks in the 5'UTR or CDS, transcripts with peaks at 3'UTR positions 1-400 were excluded. Statistical significance was determined by Kruskal-Wallis test with Dunn's correction for multiple comparisons and was determined based on comparison to the set with no 3'UTR CLIP peaks.",
    "ncbi_link": "hnRNP L: 3191
UPF1: 5976"
  },
  {
    "caption": "C Representative northern blots assaying the stability of β-globin reporter transcripts containing the SMG5 3'UTR alone or supplemented with cassettes containing the indicated RSE variants in HeLa Tet-off cells. Half-lives were determined from at least 3 independent experiments and decay curves are shown with points representing mean and standard deviation at each timepoint. Significance was measured compared to the SMG5 3'UTR reporter using the sum-of-squares F test.",
    "ncbi_link": "β-globin: 
SMG5: 23381"
  },
  {
    "caption": "D RNA immunoprecipitation experiments evaluating hnRNP L association with deletion and replacement reporter transcripts from (C). \"AS\" indicates a reporter in which the antisense sequence of the RSE was inserted in the SMG5 3'UTR in the same position as the RSE. The northern blot is representative of 3 independent experiments and quantification is presented in the accompanying bar graph with mean and standard deviation. * indicates P = 0.0146 in two-tailed Student's t-test. The reporter containing the GAP 3'UTR used here as a transfection control contains a predicted hnRNP L binding site, allowing its consistent recovery in the IPs.",
    "ncbi_link": "GAP: 
hnRNP L: 3191
SMG5: 23381"
  },
  {
    "caption": "A RNA-seq analysis of cells treated with hnRNP L siRNA or a combination of siRNAs against hnRNP L and UPF1 identifies populations of transcripts that decreased in abundance upon hnRNP L knockdown in a UPF1-dependent manner. B CDF plot of transcript 3'UTR lengths for subsets identified in (A). Statistical significance was determined by two-sided K-S test. P value for decreased set is from comparison to the set of total transcripts. P value for rescued set is from comparison to decreased set. ",
    "ncbi_link": "hnRNP L: 3191
UPF1: 5976"
  },
  {
    "caption": "A qPCR of selected transcripts found by RNA-Seq to decrease in abundance in the absence of hnRNP L. Values represent the mean and standard deviation of 3 independent biological replicates. Significance of hnRNP L KD and UPF1 KD were compared to NT, and the double knockdown was compared to hnRNP L KD. For clarity, only a single star is used to indicate significance; in all cases P ≤ 0.025 in two-tailed Student's t-tests.",
    "ncbi_link": "hnRNP L: 3191
UPF1: 5976"
  },
  {
    "caption": "B Half-lives of selected transcripts under conditions of non-targeting or hnRNP L knockdown. Measurements were calculated based on proportional recovery of transcript labeled with 5-EU in 1 hour versus total transcript. Significance was determined using two-tailed Student's t-test: *P ≤ 0.05, **P ≤ 0.01, ****P ≤ 0.0001. Values represent mean and standard deviation of 3 independent replicates.",
    "ncbi_link": "hnRNP L: 3191"
  },
  {
    "caption": "C The stability of β globin reporters with the CSRP1 3'UTR, along with several variants in which putative hnRNP L motifs in the indicated intervals were mutated, were evaluated in HeLa Tet-off cells. The schematic indicates areas of 3' UTR CA-enrichment in light blue and includes the sequence of the first 200 nucleotides of the CSRP1 3'UTR, where putative hnRNP L binding elements are in red typeface. The northern blot is a representative example from 3 independent replicates. Mean values plotted with SD at each timepoint were used to quantify decay (right panel). Significance is measured compared to the WT reporter using the sum-of-squares F test.",
    "ncbi_link": "β globin: 
CSRP1: 1465
hnRNP L: 3191"
  },
  {
    "caption": "D The stability of the WT and L mut 1-200 CSRP1 reporters in HeLa Tet-off cells treated with non-targeting RNAi or siRNA against UPF1 was evaluated. The northern blot is a representative example from at least 3 biological replicates. Decay quantification and statistics were performed as in (C), with significance measured compared to the non-targeting condition.",
    "ncbi_link": "CSRP1: 1465
UPF1: 5976"
  },
  {
    "caption": "A Motif analysis of recovered UPF1-associated transcripts analyzed by RIP-Seq Transcripts were binned into three 3'UTR length classes, which were then further subdivided based on hnRNP L motif density. Each box plot represents the median and interquartile range with extensions from 10% to 90% of the indicated subset. Dotted line represents the median RIP-Seq efficiency of the class of transcripts with the shortest 3'UTR and no hnRNP L binding motifs. Significance was computed using Kruskal-Wallis tests with Dunn's correction for multiple comparisons. B CDF plots of selected transcript classes from (A). Log2(FC) of UPF1 knockdown as compared to the non-targeting control indicates NMD sensitivity of each class. Significance was determined by Kruskal-Wallis test with Dunn's correction for multiple comparisons Data information: **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.",
    "ncbi_link": "UTR: 
hnRNP L: 3191
UPF1: 5976"
  },
  {
    "caption": "C Motif analysis of recovered UPF1-associated transcripts analyzed by RIP-Seq Transcripts are divided into tertiles by hnRNP L and PTBP1 binding motif density and 3'UTR length. Data are represented and analyzed as in (A). Dotted line represents the median RIP-Seq efficiency of the class of transcripts with the shortest 3'UTR and low PTBP1/hnRNP L motif density. D CDF plots of selected transcript classes from (C) analyzed as in (B). Data information: **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.",
    "ncbi_link": "UTR: 
hnRNP L: 3191
PTBP1: 5725
UPF1: 5976"
  },
  {
    "caption": "C qPCR of selected transcripts in SU-DHL-4 cells under conditions of non-targeting RNAi or hnRNP L knockdown with or without 50 μg/mL cycloheximide treatment (for 4 hours; n ≥ 3). Significance of hnRNP L KD + DMSO and NT + CHX were compared to NT + DMSO, and hnRNP L KD + CHX was compared to hnRNP L KD + DMSO. Bars represent the mean ± SD. For clarity, only a single star was used to indicate significance; in all cases P ≤ 0.05 in two-tailed Student's t-tests.",
    "ncbi_link": "hnRNP L: 3191"
  },
  {
    "caption": "E Half-life determination from RT-qPCR detection of reporter constructs in HeLa Tet-off cells transfected with non-targeting or UPF1 siRNAs. For plots comparing non-targeting with UPF1 knockdown, significance is compared to the non-targeting condition using the the sum-of-squares F test. The fourth plot compares the non-targeting decay curves of the three reporters, and significance is compared to the decay of the fusion transcript. Points represent the mean ± SD from qRT-PCR at each time point of at least 3 independent experiments.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "A qPCR of selected transcripts in SU-DHL-4 cells under conditions of BCL2 knockdown, hnRNP L knockdown, or non-targeting control siRNA Nucleofection (n ≥ 4 independent experiments). Bars indicate mean ± SD. Significance was determined compared to NT using two-tailed Student's t-tests. Data information: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.",
    "ncbi_link": "BCL2: 596
hnRNP L: 3191"
  },
  {
    "caption": "C qPCR of selected transcripts in SU-DHL-6 cells under conditions of hnRNP L knockdown or non-targeting control (n = 5 independent experiments). Bars indicate mean ± SD. Significance of hnRNP L KD was determined compared to NT using two-tailed Student's t-tests. Data information: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.",
    "ncbi_link": "hnRNP L: 3191"
  },
  {
    "caption": "A. Immunofluorescence microscopy of control, parental and patient fibroblasts labeled for LAMP-1. Patient fibroblasts (VPS41S285P/R662* and VPS41c.1423-2A>G/R662*) show more LAMP-1 puncta, which are distributed throughout the cell. (A') Quantification shows a significant increase in the number of LAMP-1 positive compartments for both patients. >15 Cells per condition were quantified (n=3). Scale bars, 10µm.",
    "ncbi_link": "VPS41: 27072"
  },
  {
    "caption": "D. HeLaVPS41KO cells transfected with VPS41WT-APEX2-V5, VPS41S285P-APEX2-V5 or VPS41R662*-APEX2-V5 constructs labeled for LAMP-1 and V5 immunofluorescence microscopy. All VPS41 variants co-localize with LAMP-1, indicating that VPS41S285P and VPS41R662* are recruited to late endosomes/lysosomes. Scale bars 10µm; zoom of squared area, 1µm.",
    "ncbi_link": "V5: 
APEX2: 606508
VPS41: 27072"
  },
  {
    "caption": "H. VPS41WT/WT, VPS41WT/R662* and VPS41S285P/R662* primary fibroblasts incubated with Dextran-568 for 0.5, 2, 5, 8 and 24 hours. Colocalization of Dextran-568 and SiR-Lysosome Cathepsin D (SiR-Lyso) reveals a delay in lysosomal delivery in maternal (VPS41WT/R662*) and patient (VPS41S285P/R662*) cells at 2 hours of Dextran uptake. After 5 hours, maternal cells show similar to control colocalization levels. Patient cells show only after 24 hours colocalization levels similar to control, indicating a delay rather than a block in late endosome - lysosome fusion. >10 Cells per cell line were quantified.",
    "ncbi_link": "VPS41: 27072"
  },
  {
    "caption": "A. Western blot of LC3 expression levels in control and patient fibroblasts. In steady state (0 hours) conditions, patient fibroblasts have a higher ratio of lipidated LC3 (LC3II):LC3I than control cells. Induction of autophagy by nutrient starvation (2 hours incubation with minimal EBSS medium) results in a raise in LC3II:LC3I ratio in both control and patient cells, but in VPS41S285P/R662* fibroblasts this increase is only modest (quantified in A') (n=2).",
    "ncbi_link": "VPS41: 27072"
  },
  {
    "caption": "E. Immunofluorescence of HeLaWT and HeLaVPS41KO cells transfected with LC3GFP/RFP tandem construct. The increased percentage of GFP/RFP-positive compartments in HeLaVPS41KO cells indicate a block in autophagic flux (quantified in E'). >12 Cells per cell line were quantified. Scale bars 10µm; zoom, 1µm.",
    "ncbi_link": "VPS41: 27072"
  },
  {
    "caption": "A. Immunofluorescence of control, parental and patient fibroblasts labeled for LAMP-1 and mTOR. In steady state conditions (0 hours) VPS41S285P/R662* fibroblasts show less colocalization between mTOR and LAMP-1. VPS41WT/WT, VPS41WT/S285P and VPS41WT/R662* show an appropriate mTOR response upon nutrient deprivation (2 hours) or restimulation (2 hours starvation followed by 15 minutes restimulation) (Appendix Fig S5A). >10 Cells per cell line were quantified (A'). Quantifications are performed relative to colocalization under steady state conditions per cell line (n=3). Scale bars, 10µm; zoom, 1µm.",
    "ncbi_link": "VPS41: 27072"
  },
  {
    "caption": "D. Rescue experiments of HeLaVPS41KO cells. Expression of VPS41WT-APEX2-V5, VPS41S285P-APEX2-V5 or VPS41R662*-APEX2-V5. Reintroduction of VPS41WT rescues TFE3 localization, whereas expression of mutant VPS41 has no effect (quantified in D'). >83 Cells per condition were quantified (n=3). Scale bars, 10µm.",
    "ncbi_link": "V5: 
APEX2: 606508
VPS41: 27072"
  },
  {
    "caption": "B. Western blot on cellular or secreted secretogranin II (SgII) of PC12 cells VPS41KO, or VPS41KO transduced with HA-VPS41WT or HA-VPS41S285P lentivirus. Cells were washed and incubated for 30 minutes in Tyrode's solution containing 2.5 mM K+ (basal) or 90 mM K+ (stimulated). No difference in secreted sgII levels was observed between VPS41WT and VPS41S285P.",
    "ncbi_link": "HA: 
VPS41: 27072"
  },
  {
    "caption": "C. Graph representing the percentage of animals with 6 normal dopaminergic neurons in the anterior region of Pdat-1::GFP; Pdat-1:: α-syn (strain UA44) animals with heterozygous expression of hVPS41 variants. Heterozygous expression of hVPS41WT with either variant (strains UA389 or UA390) significantly rescues neurons from α-synuclein-induced degeneration at day 7 whereas compound heterozygous expression (strain UA391) fails to rescue neurodegeneration. At day 10, none of the heterozygous backgrounds significantly rescues α-synuclein-induced neurodegeneration. n=30 Adult worms for each of 3 independent experiments for the α-synuclein (α-syn) strain (total of 90 worms) and n=90 for each independent transgenic strain (30 worms/trial x 3 independent transgenic lines = 270 worms) for each of 3 independent experiments. D. Representative images of DA neurons from C. elegans expressing Pdat-1::GFP; Pdat-1:: α-syn, with or without hVPS41 variants, as described in (C). Intact DA neurons are indicated with arrowheads and missing neurons are indicated with arrows. Scale bar 20µm. ",
    "ncbi_link": "α-syn: 
α-synuclein: 
dat-1: 
VPS41: 27072"
  },
  {
    "caption": "(E) Representative adult midgut from control esgReDDM at day 14 after temperature shift in variable demand. ECs renewed are marked positively by persistent RFP labelling (red-only cells). (F and G) Few ECs had been renewed in 'Low' midguts after 14 (F) and 21 (G) days of tracing. Data information: Scale bars, 50µm.",
    "ncbi_link": "esg: 34903"
  },
  {
    "caption": "(H-J) Age-synchronized posterior midguts of control (esgReDDM>, H) and p35 overexpression in stem and progenitor cells (esgReDDM>p35, p35 I and J) at 7 days after temperature shift. Arrows in (H, I) point to newly differentiated ECs. In (J), tumour mass is found in the anterior midgut. Data information: Scale bars, 50µm.",
    "ncbi_link": "p35: 34385
esg: 34903"
  },
  {
    "caption": "(K), Quantification of mitosis PH3+ cells in posterior midgut (pmg) (control: gut scored n=13 and esg>p35, p35: n=22]). Student t-test (**** = P < 0.0001). Data information: In the boxplots, the box extends from the 25th to 75th percentiles and whiskers show all points, min to max.",
    "ncbi_link": "p35: 34385
esg: 34903"
  },
  {
    "caption": "(L), Diap1 is monitored by the GFP.4.3. (green) reporter (Djiane et al., 2013; Zhang et al., 2008). Diap1-GFP is detected in a subset of adult midgut esg+ cells that are negative for the mitotic marker PH3 (red, inset) and for EE marker Prospero (Pros, grey in inset). Diap1-GFP is not detected in mature EC (large nuclei cells, DAPI in blue). Data information: Scale bars, 50µm.",
    "ncbi_link": "esg: 34903"
  },
  {
    "caption": "(C) Control GBE-Su(H)ReDDM> and (D) GBE-Su(H)ReDDM>p35, p35 midguts after 7 days of tracing. Data information: Scale bars, 100µm",
    "ncbi_link": "p35: 34385"
  },
  {
    "caption": "(F-J) Adult midguts of (F) control kluReDDM> (G) kluReDDM>Debcl-RNAi, (H) kluReDDM>Drice-RNAi, (I) kluReDDM>Diap1-RNAi, (J) kluReDDM>Diap1 midguts after 7 days of tracing. The arrows point to examples of PH3+ labelled ISCs. Data information: Scale bars, 100µm",
    "ncbi_link": "Debcl: 53585
Diap1: 39753
Drice: 43514
klu: 39228"
  },
  {
    "caption": "(N) Quantification of klu+ cells and renewed ECs in kluReDDM>Diap1 posterior midguts (n=8) relative to 'Low' control in K and L, respectively. Data information: ox and whisker plot showing min to max values and the box is extending from the 25th to 75th percentiles. The line in the middle of the box is plotted at the median. P values (*, P<0.0261; **, P<0.005; ***, P<0.0021) calculated by one-way ANOVA with Bonferroni correction.",
    "ncbi_link": "Diap1: 39753
klu: 39228"
  },
  {
    "caption": "(A-E) Confocal images of representative midguts of the indicated genotypes using kluReDDM for tracing and age- and EB-specific transgene expression at day 7 after temperature shift. ISC mitosis was monitored by using PH3 labelling (white) in all guts. (B-E) Accumulation and loss of klu+ cells by loss (B and E) and gain (C and D) of N and EGFR signalling. In (C), the accumulation of EC-committed EBs (klu+ cells) in midguts with constitutively activated EGFR (kluReDDM> EGFRact) is accompanied with a non-autonomous increase in ISC mitosis. Inset in (C) shows labelling with Dl (blue), revealing symmetric ISC mitoses Data information: Scale bar, 100µm for all images.",
    "ncbi_link": "klu: 39228"
  },
  {
    "caption": "Confocal images of representative midguts of the indicated genotypes Rescue of the loss of EBs induced by gain of Notch (H-RNAi) by expressing Debcl-RNAi. Data information: Scale bar, 100µm for all images.",
    "ncbi_link": "Debcl: 53585"
  },
  {
    "caption": "Confocal images of representative midguts of the indicated genotypes escue of the loss of EBs induced by loss of EGFR (EGFRDN) by expressing Debcl-RNAi. (J and K) Impact of gain of expression (J) and loss by RNAi expression (K) of lz using kluReDDM White arrowheads point to examples of mitosis labelled by PH3+. (L and M) Impact of gain of expression (L) or loss by RNAi expression (M) of klu (M) using kluReDDM. Data information: Scale bar, 100µm for all images.",
    "ncbi_link": "Debcl: 53585
klu: 39228
lz: 31883"
  },
  {
    "caption": "(N-R) Images of representative midguts of esgReDDM at day 7 after temperature shift of the indicated genotypes. PH3 labelling (white) detected rare mitoses in the mutant genotypes. Data information: Scale bar, 100µm for all images.",
    "ncbi_link": "esg: 34903"
  },
  {
    "caption": "(D) Quantification of the number of Diap1-GFP+. Note that in p35-expressing midguts reared in 'Low', GFP levels are not increased, consistent with the p35 protein suppressing apoptosis downstream of Diap1. Data information (n= 17, 13, 12, 10, 21, 24). P values were calculated using one-way ANOVA Bonferroni corrected (****, P < 0,0001).",
    "ncbi_link": "p35: 34385"
  },
  {
    "caption": "F: Co-IP of clathrin with Venus-tagged HURPWT and HURP∆MUT constructs in asynchronous and mitotic HeLa cells.",
    "ncbi_link": "Venus: 
HURP: 9787"
  },
  {
    "caption": "G Co-IP of clathrin with Venus-tagged HURPWT, HURP∆MUT and HURPS839A constructs in mitotic HeLa cells.",
    "ncbi_link": "Venus: 
HURP: 9787"
  },
  {
    "caption": "H: Representative images of HURPWT, HURP∆MUT and HURPS839A in the different mitotic stages.",
    "ncbi_link": "HURP: 9787"
  },
  {
    "caption": "I-J: RNAi rescue experiments (n=2), which included the knockdown of endogenous HURP and re-expressing either RNAi resistant HURPWT, HURP∆MUT and HURPS839A. In order to assess mitotic behaviour of the cells, the time required of control, HURP knockdown, HURPWT, HURP∆MUT and HURPS839A HeLa cells to progress through mitosis (NEBD-anaphase) was established using time-lapse microscopy. Every circle represents one analysed cell. The number of cells analysed is indicated as n in I. Mann-Whitney test was performed to assess significant differences in the median time required for mitotic progression (*: p-value≤0.05, ***: p-value: ≤0.001, ****: p-value ≤0.0001; ns: non-significant)",
    "ncbi_link": "HURP: 9787"
  },
  {
    "caption": "F  Immunoblot  analysis of ectopic HIF2α protein levels in 293T  cells with gradually increased amount of ectopic USP33. 0.5 µg of HA-tagged  HIF2α plasmids together with the increased amounts of GFP-tagged  USP33  plasmids (0, 0.1, 0.2 or 0.3 μg) were introduced into  293T  cells. Forty-eight hours post transfection, levels of ectopic  HIF2α-HA and GFP-USP33 were analyzed by  immunoblot analysis. Concomitantly increased levels of ectopic  HIF2α and USP33 expression  indicated the positive regulation of HIF2α protein by  USP33. G Immunoblot  analysis of ectopic  HIF2α protein levels in 293T cells expressing ectopic wild type (WT) USP33 or the catalytically dead (CD)  USP33. HA-tagged  HIF2α plasmids (0.5 µg) were introduced into 293T  cells alone or together with  GFP-tagged WT or CD USP33  plasmids (0.2 µg). Levels of ectopic HIF2α-HA and GFP-USP33 were analyzed 48 hours post transfection. Expression  of the wild type USP33 but not the catalytically dead USP33 increased the ectopic  HIF2α  protein levels.",
    "ncbi_link": "GFP: 
HA: 
HIF2α: 2034
USP33: 23032"
  },
  {
    "caption": "G Co-immunoprecipitation to detect the interaction between HIF2α  and the wild-type (WT) or the catalytically dead (CD) USP33. Ectopic HA-tagged HIF2α  were expressed in 293T  cells with GFP-tagged wild-type or catalytically dead USP33. Cell lysates were subjected to immunoprecipitation  with anti-HA antibodies. Co-immunoprecipitated products immunoblotted with the indicated antibodies. The catalytically dead USP33  relative to the wild type USP33   showed a stronger affinity to HIF2α.",
    "ncbi_link": "GFP: 
HA: 
HIF2α: 2034
USP33: 23032"
  },
  {
    "caption": "G Co-immunoprecipitation to determine the  serine phosphorylation sites in human HIF2α responsible for its binding to USP33. Ectopic  GFP-tagged  USP33 along with HA-tagged wild type  HIF2α or HIF2α mutants with indicated  serine to  alanine point mutations were expressed in 293T cells. Cell lysates were subjected to  immunoprecipitation  with anti-HA agaroses Co-immunoprecipitated products were immunoblotted with the indicated antibodies. The S484A mutation largely attenuated the  interaction of HIF2α with  USP33, indicating that the  serine  484 site in HIF2α was the most important  phosphorylation site for the interaction  between  HIF2α and  USP33.",
    "ncbi_link": "GFP: 
HA: 
HIF2α: 2034
USP33: 23032"
  },
  {
    "caption": "B Representative images of   tumorsphere formation of T387  GSCs expressing USP33-targeting shRNA (shUSP33) or non-targeting shRNA (shNT). Twenty-four hours after  lentiviral infection, T387 GSCs expressing shUSP33 or shNT were planted in 96 well plates at the density of 2,000 cells per well and cultured for 48 hours under normoxia (20%  O2) or  hypoxia (5%  O2). Disruption of USP33 inhibited GSC tumorsphere  formation in normoxia  and dramatically suppressed  GSC tumorsphere  formation in hypoxia. Scale bar, 200 μm.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "E Cell titer  assays showing cell growth  of T387 GSCs expressing shUSP33 or shNT in normoxia or  hypoxia. GSCs were transduced with shNT or shUSP33  through lentiviral infection for 24 hours, and then split into 96 well plates at the concentration of 2,000 cells per well. Cell titer  was determined by the Glo luminescent cell viability assay  kit (Promega) at the indicated time points. Disruption of USP33 inhibited GSC growth in normoxia and hypoxia. The experiment has been repeated three times. The presented curves were based on three technical replicates. *, p < 0.05; **, p < 0.01; ***, p < 0.001 (mean ± s.e.m.; two tailed unpaired t-test).",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "F Representative  immunofluorescent staining of the apoptotic marker cleaved  caspase 3 in T387  GSCs  expressing shUSP33 or shNT in normoxia or hypoxia. GSCs  were attached to hESC-Qualified Matrix (Corning) in 6-well plates at the concentration of 50,000 cells per well. Forty-eight hours post infection with shUSP33 or shNT  lentiviruses, cells were  stained for cleaved caspase 3 (green) and nuclei  (blue). Scale bar, 80 μm.",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "C, Representative images of autonomous fluorescent signals of  4HRE-d2GFP in xenografts derived from or shUSP33- or shNT- expressing T387 GSCs  transduced with 4HRE-d2GFP. Scale bar, 200 μm.",
    "ncbi_link": "d2GFP: 
USP33: 23032
4HRE: 7422"
  },
  {
    "caption": "E, Representative images of autonomous fluorescent signals of 4HRE-d2GFP (green) and  immunofluorescent staining of the  stem cell  marker SOX2 (red) in xenografts  derived from T387  GSCs transduced with 4HRE-d2GFP. More GFP signals were detected in the  SOX2+ cells compared with the SOX2- cells, suggesting a stronger  hypoxia response in GSCs relative to NSTCs. Scale bar, 200 μm.",
    "ncbi_link": "d2GFP: 
SOX2: 6657
4HRE: 7422"
  },
  {
    "caption": "G, Representative images of immunofluorescent staining  of the apoptotic marker cleaved caspase 3  (red) and autonomous fluorescent signals of 4HRE-d2GFP (green) in xenografts  derived from T387 GSCs transduced with 4HRE-d2GFP. The  GFP+ population had much less apoptosis   relative to the GFP- population, suggesting that hypoxia  response inhibited  cell apoptosis. Scale bar, 200 μm.",
    "ncbi_link": "d2GFP: 
GFP: 
4HRE: 7422"
  },
  {
    "caption": "B Kaplan-Meier survival curves of mice bearing GBMs  derived from T387 GSCs  expressing shUSP33 or shNT from (A). Disruption of USP33  extended the survival  of mice bearing GSC-derived GBM tumors. (n= 5  mice for each group; shUSP33#42 vs shNT, p = 0.0185; shUSP33#45 vs shNT, p = 0.0027; two-tailed log-rank test).",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "E, F  Immunofluorescent  analysis (E) and statistical quantifications (F) of the cell proliferation marker Ki67  in xenografts  derived from T387 GSCs expressing shUSP33 or shNT. Disruption of USP33 in  GSCs reduced cell proliferation  in GBM xenografts. Scale bar, 80 μm. (n = 5 tumors for each group; ***, p < 0.001; mean ± s.e.m.; two tailed unpaired t-test).",
    "ncbi_link": "USP33: 23032"
  },
  {
    "caption": "(B) Representative fluorescent images (red) showing that mouse primary cortical neurons were transduced with shRNA-control or shATIC #6 at DIV 3 and then transfected with MYC-LRRK2-WT and DsRed at a plasmid ratio of 10:1 at DIV 5. Neuronal viability was analyzed at 72-hour post-transfection with non-viable neurons exhibiting no obvious neurite process (arrow). Scale bars, 100 μm. (C) Quantification of neuronal viability. Bars indicate the viability (n > 100) for each transfection condition expressed as a percent of control neurons (DsRed with pcDNA3.1 empty vector). Data represent the mean ± SEM from three independent experiments with n > 100 cells quantified in each experiment. **p < 0.01, ***p < 0.001 by one-way ANOVA followed by a Tukey's post hoc test.",
    "ncbi_link": "DsRed: 
MYC: 
ATIC: 108147
LRRK2: 120892"
  },
  {
    "caption": "(D and E) Endogenous LRRK2 levels in ATIC overexpression cells. SH-SY5Y cells were transfected with V5-ATIC or empty vector. After 48 hours, LRRK2 expression levels were analyzed by Western blot. Images were quantified by ImageJ software. Data are mean ± SEM, n=3 independent experiments. ***p < 0.001 by Student's t tests.",
    "ncbi_link": "V5: 
ATIC: 471"
  },
  {
    "caption": "(H and I) Endogenous LRRK2 levels in ATIC KO cells upon LV-flag-ATIC expressing. SH-SY5Y WT or ATIC KO cells were infected with lentiviruses carrying Flag-ATIC or empty vector. After 48 hours, LRRK2 expression levels were analyzed by Western blot. Images were quantified by ImageJ software. Data are the means ± SEM, n=3 independent experiments. ***p < 0.001 by one-way ANOVA followed by a Tukey's post hoc test.",
    "ncbi_link": "flag: 
Flag: 
ATIC: 471"
  },
  {
    "caption": "(A and B) Overexpressed LRRK2 levels in HEK 293T cells upon AICAr treatment. HEK293 cells were transfected with MYC-LRRK2 and treated with or without 1mM AICAr for 48 hours. LRRK2 levels were analyzed by Western blot.",
    "ncbi_link": "MYC: 
LRRK2: 120892"
  },
  {
    "caption": "(S) Representative fluorescent images (green) showing that mouse primary cortical neurons were co-transfected with MYC-LRRK2 WT or G2019S (GS), and eGFP at a plasmid ratio of 10:1 at DIV 5, and treated with or without 1mM AICAr. Neuronal viability was analyzed at 48-hour post-transfection with non-viable neurons exhibiting no obvious neurite process (arrow). Scale bars, 100 μm. (T) Quantification of neuronal viability. Bars indicate the viability (n > 100) for each transfection condition expressed as a percent of control neurons (eGFP with pcDNA3.1 empty vector). Data represent the mean ± SEM from three independent experiments with n > 100 cells quantified in each experiment. *p < 0.05, ***p < 0.001, ****p < 0.0001 by one-way ANOVA followed by a Tukey's post hoc test.",
    "ncbi_link": "eGFP: 
MYC: 
LRRK2: 120892"
  },
  {
    "caption": "(C) LRRK2 and GBA mRNA levels upon AICAr treatment. SH-SY5Y cells were treated with or without 2mM AICAr for 24 hours. Total RNA was extracted. LRRK2 and GBA mRNA levels were analyzed by real-time PCR. Data are mean ± SEM, n=4 independent experiments. **p < 0.01 by Student's t tests. ns: not statistically significant. (D) LRRK2 mRNA level upon AICAr treatment in the presence of actinomycin D. SH-SY5Y cells were treated with or without 2mM AICAr for 24 hours and in the presence of 10μg/ml actinomycin D. Total RNA was extracted. LRRK2 mRNA levels were analyzed by real-time PCR. Data are mean ± SEM, n=4 independent experiments. **p < 0.01, ****p < 0.0001 by two-way ANOVA followed by Sidak's multiple comparison test.",
    "ncbi_link": "GBA: 106627981
LRRK2: 120892"
  },
  {
    "caption": "(E and F) LRRK2 expression levels from native LRRK2 cDNA and synthesized LRRK2 cDNA with synonymous codons upon AICAr treatment. HEK 293T cells were transfected with Flag-LRRK2 with native cDNA or with synthesized cDNA, and treated with or without 1mM AICAr for 48 hours. LRRK2 expression levels were analyzed by Western blot. Images were quantified by ImageJ software. Data are mean ± SEM, n=3 independent experiments. ***p < 0.001 by Student's t tests.",
    "ncbi_link": "Flag: 
LRRK2: 
LRRK2: 120892"
  },
  {
    "caption": "(I and J) The specific region (2221-3927bp) of the synthesized Flag-LRRK2 cDNA was replaced with the native sequence and the response of this chimeric LRRK2 cDNA expression to AICAr treatment was analyzed by Western blot. Images were quantified by ImageJ software. Data are mean ± SEM, n=3 independent experiments. ****p < 0.0001 by Student's t tests.",
    "ncbi_link": "Flag: 
LRRK2: "
  },
  {
    "caption": "(B LRRK2 protein levels in AUF1 knockout (KO) cells upon AICAr treatment. SH-SY5Y WT and AUF1 KO cells were treated with or without 1mM AICAr for 48 hours. LRRK2 expression levels were analyzed by Western blot.",
    "ncbi_link": "AUF1: 3184"
  },
  {
    "caption": "(E and F) LRRK2 protein levels in AUF1 KO cells with AUF1 expressing back upon AICAr treatment. SH-SY5Y WT and KO cells were transfected AUF1-GFP or GFP and selected with 4μg/ml blasticidin. The resulting stable cell lines were treated with or without 1mM AICAr for 48 hours. LRRK2 expression levels were analyzed by Western blot.",
    "ncbi_link": "GFP: 
AUF1: 3184"
  },
  {
    "caption": "(G and H) Overexpressed LRRK2 levels in AUF1 KO cells with AUF1 expressing back upon AICAr treatment. SH-SY5Y WT and AUF1 KO cells were transfected AUF1-GFP or GFP and selected with 4μg/ml blasticidin. The resulting cell lines were transfected with a construct with native LRRK2 cDNA or synthesized LRRK2 cDNA with synonymous codons and treated with or without 1mM AICAr for 48 hours. LRRK2 expression levels were analyzed by Western blot. Images were quantified by ImageJ software.",
    "ncbi_link": "GFP: 
LRRK2: 
AUF1: 3184
LRRK2: 120892"
  },
  {
    "caption": "(A and B) AUF1 binds to LRRK2 mRNA upon AICAr treatment. SH-SY5Y WT and AUF1 KO cells were treated with or without 1mM AICAr for 24 hours. RNA and protein complexes were immunoprecipitated using AUF1 antibody. The LRRK2 mRNA levels were analyzed by semiquantitative reverse transcription (RT)-PCR. 18S ribosomal RNA (rRNA) was as a loading control. Images were quantified by ImageJ software. Data are mean ± SEM, n=3 independent experiments. *p < 0.05 by Student's t tests.",
    "ncbi_link": "AUF1: 3184
LRRK2: 120892"
  },
  {
    "caption": "(D) Direct interaction of LRRK2 mRNA and four AUF1 isoforms. Biotin-labelled 62-nt LRRK2 RNA probes from native LRRK2 cDNA or synthesized LRRK2 cDNA were incubated with purified AUF1 isoforms in an RNA electrophoretic mobility shift assay (EMSA). Free probes and AUF1 bound probes were detected using a chemiluminescent RNA EMSA kit.",
    "ncbi_link": "LRRK2: 
LRRK2: 120892"
  },
  {
    "caption": "(E) LRRK2 mRNA decapping by DCP1A and DCP2. Recombinant DCP1A and DCP2 proteins were purified from HEK 293T cells and incubated with [α-32P]cap-labeled LRRK2 RNA. LRRK2 mRNA decapping was analyzed by one-dimensional thin layer chromatography. The decapping activity is demonstrated by the increased m7GDP levels.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(E and F) LRRK2 protein levels upon the treatment of 1mM AICAr in WT and AMPK KO SH-SY5Ycells for 48 hours. LRRK2 expression levels were analyzed by Western blot. Images were quantified by ImageJ software.",
    "ncbi_link": "AMPK: 5564///51422///5571///5565///53632///5563///5562"
  },
  {
    "caption": "(B) Representative confocal images (GFP) of dopamine neurons in each cluster from 9-week-old WT and LRRK2-G2019S transgenic flies with or without 1mM AICAr treatment after posteclosion. Scale bars, 25 μm.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(C-E) Quantification of dopamine neurons per DA cluster in 9-week-old WT and LRRK2-G2019S transgenic flies with or without 1mM AICAr treatment after posteclosion. (F) Total numbers of dopamine neurons in four major DA clusters of 9-week-old WT and LRRK2-G2019S transgenic flies with or without AICAr treatment after posteclosion. Data are mean ± SEM, n=12 flies per group. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by one-way ANOVA followed by a Tukey's post hoc test.",
    "ncbi_link": "LRRK2: 120892"
  },
  {
    "caption": "(A) Representative images of DAneuron staining. WT and LRRK-KO mice were injected with 1ul LPS (5ug/animal) or phosphate buffered saline (PBS) into the substantia nigra pars compacta (SNpc) and administrated with AICAr (2.4μg/day/animal) or saline to same stereotaxic coordinates using osmotic pumps. After 21 days of injection, DA neurons were stained by anti-tyrosine hydroxylase (TH) antibody. Scale bars, 500 μm.",
    "ncbi_link": "LRRK: 66725"
  },
  {
    "caption": "(E) CD68 levels in WT and LRRK-KO mice injected with 1μl LPS (5μg/animal) or PBS into striatum followed by administration of AICAr (2.4μg/day/animal) or saline to same stereotaxic coordinates using osmotic pumps. After 21 days of injection, LRRK2 and CD68 expression in striatal tissues near the needle sites was analyzed by Western blot. (F) Quantification of images from (E) using ImageJ software, n=3 animals per group.",
    "ncbi_link": "LRRK: 66725"
  },
  {
    "caption": "a, A TRPML1Va-expressing HEK293T cell showed a large inwardly rectifying whole-cell current elicited by voltage steps (from -140 mV to +80 mV in increments of 20 mV) in the standard extracellular (Tyrode's) bath solution. Step duration, 90 ms; holding potential, 0 mV; Vm, membrane potential.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "d, pH-dependence of IFe/TRPML1Va. Whole-cell currents were elicited by repeated voltage ramps (-100 to +100 mV; 400 ms) with a 4-s interval between ramps. Only a portion of the voltage protocol is shown. Holding potential, 0 mV.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "e, Large IFe/TRPML2Va was seen in the presence of 30 and 105 mM Fe2+ (pH 4.6).",
    "ncbi_link": "TRPML2: 255231"
  },
  {
    "caption": "f, Little or no IFe was seen in a TRPML3Va-expressing cell.",
    "ncbi_link": "TRPML3: 55283"
  },
  {
    "caption": "a, Current densities (mean ± s.e.m., n = 4-10) of IFe (30 mM Fe2+, pH 4.6) for TRPML1Va and ML4 mutant TRPML1Va channels. Asterisk indicates statistical difference (P < 0.01) compared to TRPML1Va.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "b, 55Fe2+uptake (normalized) in HEK293T cells transfected with vector control, with TRPML1Va, with F408D-TRPML1Va and with T232P-TRPML1Va constructs. Error bars indicate the standard deviation on the basis of two independent triplicate experiments.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "c, [Fe2+]o-dependent quenching of Fura-2 fluorescence in TRPML1Va-transfected cells (arrows), but not in non-transfected control cells (arrowheads) or T232P-TRPML1Va-transfected cells (bottom row). The fluorescence intensity was measured at an excitation wavelength of 360 nm (F360). The original magnification used for all micrographs was ×200.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "d, Average normalized responses of EGFP-positive TRPML1Va-transfected cells (typically n = 20-40 cells) to 1 or 10 mM Fe2+ (pH 4.6).",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "e, No significant quenching was seen in T232P-TRPML1Va-transfected cells.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "f, Slightly less quenching was observed for the F408Dgr;-TRPML1Va-expressing cells.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "c, Lysosomal ITRPML1Va. Switching from lysosome-attached to (lysosome) luminal-side-out configuration significantly reduced the amplitude of the current. The luminal-side-out patch was exposed to the Tyrode's solution. A Cs+-based solution (147 mM Cs-methanesulphonate (Cs-MSA)) was used as a pipette solution for both configurations.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "d, NMDG+-impermeable lysosomal ITRPML1Va was much larger in the absence of divalent cations (nominal divalent-free). e, Lowering pH potentiated lysosomal ITRPML1Va. f, IFe/TRPML1Va induced by 30 mM and 105 mM Fe2+.",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "g, Whole-lysosome current in an enlarged lysosome expressing wild-type TRPML1. The pipette (lumen) solution contained nominal divalent-free Tyrode solution. A Cs+-based bath solution (147 mM Cs-MSA) was used. h, Whole-lysosome ITRPML1Va. i, Whole-lysosome IFe/TRPML1. The pipette (lumen) solution contained 105 mM Fe2+ (pH 4.6).",
    "ncbi_link": "TRPML1: 57192"
  },
  {
    "caption": "a, Cultured TRPML1-/- (ML1-/-) skin fibroblasts showed less de-quenching of the iron-sensitive fluorescence than ML1+/- cells did. De-quenching was achieved by preloading the fibroblasts with an iron-sensitive dye, Phen Green SK (PG SK), and then adding the membrane-permeable transition metal chelator, 2,2′-bipyridyl (BPD). 2,2′-BPD is predicted to chelate free cellular iron (also referred to as chelatable or labile iron), which subsequently increases PG SK fluorescence. The original magnification used was ×200",
    "ncbi_link": "ML1: 57192
TRPML1: 57192"
  },
  {
    "caption": "b, The average 2,2′-BPD induced normalized change of fluorescence (Dgr;F/F0) for ML4 cells (ML1-/-; n = 6 experiments) is significantly (asterisk, P < 0.01) lower than for the parental ML1+/- cells. Fibroblast cells (n = 10-20) were analysed for each individual experiment. 4,4′-BPD, a 2,2′-BPD analogue that cannot bind Fe2+, did not induce any significant restoration of PG SK fluorescence. Error bars, s.e.m.",
    "ncbi_link": "ML1: 57192"
  },
  {
    "caption": "c, An ML1-/- skin fibroblast cell showed autofluorescence in LAMP1-positive compartments. Autofluorescence (green) was detected within a range of excitation wavelengths (shown with excitation at 480 nm). No significant autofluorescence was observed for a ML1+/+ cell. Lysosomes were stained with a LAMP1 antibody (red). Differential interference contrast (DIC) images are shown for comparison.",
    "ncbi_link": "ML1: 57192"
  },
  {
    "caption": "Sexing the established ESCs by detecting the Y-linked Zfy gene using genomic DNA (gDNA)-qPCR, normalized to Gapdh. n.d.: not detected. Average of presumed males was set to 1.",
    "ncbi_link": "Gapdh: 14433
Zfy: 22768"
  },
  {
    "caption": "DNA-FISH detection of the number of X-linked Atrx gene foci. Representative images of the DNA-FISH are shown. Nuclei are surrounded by white dotted lines. Magenta: Atrx (white arrowheads), cyan: DAPI. N>100.",
    "ncbi_link": "Atrx: 22589"
  },
  {
    "caption": "Nanog HR assay. The percentage of GFP-positive colonies after gene targeting to the Nanog locus is shown. The results for each cell line are shown at right.",
    "ncbi_link": "GFP: 
Nanog: 71950"
  },
  {
    "caption": "Nanog expression confirmed by RNA-seq.",
    "ncbi_link": "Nanog: 71950"
  },
  {
    "caption": "Detection of the number of X-linked Atrx gene foci by DNA-FISH in GFP-positive subclones of the Nanog-targeting assay (nine independent clones, N> 100 each), performed as described in Figure 1C.",
    "ncbi_link": "GFP: 
Atrx: 22589
Nanog: 71950"
  },
  {
    "caption": "Sexing of established ESCs (gDNA-qPCR, Zfy/Gapdh), performed as described in Figure 1B.",
    "ncbi_link": "Gapdh: 14433
Zfy: 22768"
  },
  {
    "caption": "Detection of the number of X-linked Atrx gene foci by DNA-FISH with or without dox addition for 96 h (N >100), performed as described in Figure 1C.",
    "ncbi_link": "Atrx: 22589"
  },
  {
    "caption": "Detection of the Xist cloud in #B3 by RNA-FISH, with or without dox addition for 96 h ( N >200 each). A representative image is shown [magenta: Xist (white arrowhead), cyan: DAPI. Scale bar: 10 μm].",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Allele-distinguishable RT-PCR for detecting Hprt, G6pdx, and Rnf12 X-linked genes. Bands with the anticipated sizes expressed from XJF1 or XTX alleles are shown.",
    "ncbi_link": "G6pdx: 14381
Hprt: 15452
Rnf12: 19820"
  },
  {
    "caption": "Nanog HR assay. The percentage of GFP-positive colonies after gene targeting to the Nanog locus is shown as described in Figure 2C. #B2 or #B3 were cultured with or without dox addition for 96 h. The combined number of GFP-positive cells and total colonies from all experiments are listed and summarized at right.",
    "ncbi_link": "GFP: 
Nanog: 71950"
  },
  {
    "caption": "Detection of the Xist foci by RNA-FISH, with or without dox addition for 96 h (N >200 each). A representative image with percentage of Xist-positive cells is shown [magenta: Xist, cyan: DAPI.].",
    "ncbi_link": "Xist: 213742"
  },
  {
    "caption": "Detection of the number of X-linked Atrx gene foci by DNA-FISH, with or without dox addition for 96 h (N >100 each), performed as described in Figure 1C.",
    "ncbi_link": "Atrx: 22589"
  },
  {
    "caption": "Estimated repair events. The flow cytometry plots are shown in Figure EV4. The percentage of GFP-positive cells in TX-DRGFP#11 and TX-EJ5GFP#23 was normalized to the transfection efficiency detected by the VENUS expression vector. Dox (-) was set to 1 and the ratio of relative GFP-positive cells is shown (n=3).",
    "ncbi_link": "DRGFP: 
EJ5GFP: 
GFP: 
VENUS: "
  },
  {
    "caption": "Brcc3 expression confirmed by RNA-seq [biological replicates (n=3) with three different cell lines (male: #A6, #A13, #A17; female: #A4, #A10, #A11)].",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Brcc3 expression confirmed by RT-qPCR [biological replicates (n=3) with three different cell lines (male: #A6, #A13, #A17; female: #A4, #A10, #A11)].",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Confirmation of Brcc3 expression from knockdown samples in by RT-qPCR (technical duplicates)",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Nanog HR assay with Brcc3 knockdown (three biological replicates). The percentage of GFP-positive colonies after gene targeting to the Nanog locus is shown, as shown in Figure 2C. The combined number of GFP-positive cells and total number of colonies are shown (please note that total cell number of #A13 for drug screening was 3.67×107 because of contamination of 1 out of 12 dishes, compared with the other colonies for which 4×107 cells were used).",
    "ncbi_link": "GFP: 
Brcc3: 210766
Nanog: 71950"
  },
  {
    "caption": "Kaplan-Meier curves for the overall survival of breast cancer patients based on BRCC3 (A), XIST (B), and BRCC3/XIST(C) expression levels. HR: hazard ratio.",
    "ncbi_link": "BRCC3: 210766
XIST: 213742"
  },
  {
    "caption": "(E) S-phase mock and ZIKV  infected control and Cep63gt/gt MEFs co-stained for Centrin  (green) and flavivirus envelope  (red). (F) Quantification of the percentage of mock or ZIKV-infected Het and Cep63gt/gt MEFs  in S phase with greater than four Centrin  foci. Bars represent the mean ± SD normalized to the control. Asterisk denotes p<0.005 (Student's t test). Three biological replicates are represented. Data information: Scale bars indicate 5μm for all images. All cells were fixed 16 hours post infection (hpi),",
    "ncbi_link": "Cep63: 28135"
  },
  {
    "caption": "(C) We expressed Myc-tagged Brazilian Zika NS3  in 293T/17 cells and immunoprecipitated c-Myc. Precipitated proteins were probed for the Myc  tag of NS3  and endogenous CEP63. The centriole  distal end component, CP110  served as a negative control. Asterisk denotes specific band for CEP63.",
    "ncbi_link": "Myc: 
NS3: 7751225"
  },
  {
    "caption": "(G) HeLa  cells transfected with Control or Myc-tagged Brazilian ZIKV NS3  (Br NS3) co-stained for Myc  (red) and Centrin  (green). Data information: Scale bars indicate 5μm for all images.",
    "ncbi_link": "Myc: 
NS3: 7751225"
  },
  {
    "caption": "(H) Quantification of the percentage of control and NS3  expressing HeLa  cells with greater than four Centrin  foci. Bars represent the mean ± SD normalized to the control. For all quantifications at least 100 cells were counted per experiment (biological replicates=3). p<0.005 (paired Student's t test) for the comparison of NS3  to mock transfected cells was denoted with asterisk.",
    "ncbi_link": "NS3: 7751225"
  },
  {
    "caption": "(D) RT-ddPCR of IFNβ  transcript at the indicated time points in mock and ZIKV-infected H4  cells. Bars represent the mean ± SD normalized to the control. Asterisk denotes p<0.005 (Student's t test). Three biological replicates are represented.",
    "ncbi_link": "IFNβ: 3456"
  },
  {
    "caption": "(E) Control and Cep63gt/gt MEFs  were co-stained with antibodies to γ-tubulin (red) and p-Tbk1  (green). Data information: Scale bars indicate 5μm for all images.",
    "ncbi_link": "Cep63: 28135"
  },
  {
    "caption": "(F) Immunoblot  analysis of control and Cep63gt/gt MEFs  probed with antibodies to Tbk1  and p-Tbk1. Actin  served as a loading control.",
    "ncbi_link": "Cep63: 28135"
  },
  {
    "caption": "(J) SC  and CEP63  siRNA treated HeLa  cells were  co-stained for Centrin  (red) and DTX4  (green). Data information: Scale bars indicate 5μm for all images.",
    "ncbi_link": "CEP63: 80254"
  },
  {
    "caption": "(K) TBK1  or c-Myc (negative control) were immunoprecipitated  from Control or Cep63 mutant MEFs. Precipitating proteins were probed with antibodies to TBK1  and K48-linked ubiquitin.",
    "ncbi_link": "Cep63: 28135"
  },
  {
    "caption": "M2-induced human monocyte-derived macrophages were treated with 100 nM of the indicated drug either continuously for 48h, or initially for 2h in the presence or absence of FA-glucosamine (competition) followed by 46h in the absence of drug (2+46h), as described in Fig 1. mRNA levels of profibrotic markers, Arg1 (A), CD206 (B) and CD163 (C) Changes in both sets of cytokines were inhibited by blockade of unoccupied folate receptors with excess FA-glucosamine (2+46h, competition).",
    "ncbi_link": "Arg1: 383
CD163: 9332
CD206: 4360"
  },
  {
    "caption": "BALF was collected on day 21 and centrifuged to isolate cell pellets. Cells (primarily macrophages) were analyzed by qPCR for Arg1 (C), MMP9 (D), TIMP3 (E)",
    "ncbi_link": "Arg1: 11846
MMP9: 17395
TIMP3: 21859"
  },
  {
    "caption": "BALF was collected on day 21 and centrifuged to isolate cell pellets. Cells (primarily macrophages) were analyzed by qPCR for CD86 (F) and IRAK4 (G) (n=5).",
    "ncbi_link": "CD86: 12524
IRAK4: 266632"
  },
  {
    "caption": "(E) Representative photos of  iWAT,  eWAT  and BAT from  Ftoflox/flox and FtoAKO mice fed a HFD. Scale bar, 1 cm. (F) Representative H&E staining  of iWAT, eWAT  and BAT from  Ftoflox/flox and  FtoAKO mice fed a HFD. Scale bar, 200 μm. ( ",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(I-K) Serum  levels of glucose (I), triglyceride (J) and free fatty acid (FFA) (K) in Ftoflox/flox and FtoAKO mice  fed a  HFD followed by fasting. Data information: The data were presented as the mean ± SD (n = 6). Statistical analyses were performed using Student t‐test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(A)  O2  consumption of 16-week-old Ftoflox/flox and FtoAKO mice fed a HFD. White and gray areas in the graphs indicate  day  and night, respectively. (B)  CO2  generation of 16-week-old  Ftoflox/flox and FtoAKO mice fed a HFD. White and gray areas in the graphs indicate day and  night, respectively. ( Data information: The data were presented as the mean ± SD of n = 6 mice per group or triplicate tests (n = 3). Statistical analyses were performed using Student t‐test. ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(F)  qPCR  analysis of genes involved in thermogenesis,  mitochondrial  biogenesis and adipogenesis in iWAT of Ftoflox/flox and  FtoAKO mice.",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(G)  Western blot  analysis of the protein levels of UCP1, PPARGC1A and  PPARG in iWAT of Ftoflox/flox and FtoAKO mice.",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(I) Immunofluorescence detection of  UCP1 in iWAT from Ftoflox/flox and FtoAKO mice following 6 days cold exposure (4°C). Scale bar, 20 μm.",
    "ncbi_link": "Fto: 26383"
  },
  {
    "caption": "(C) The  O2 consumption rate (OCR) in differentiated beige adipocytes from  3T3-L1 cells overexpressing Vec or HIF1A  plasmid. The average basal and maximal respiration rates are shown in right panel. Data information: The data were presented as the mean ± SD of triplicate tests (n = 3). Statistical analyses were performed using Student t‐test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "HIF1A: 15251"
  },
  {
    "caption": "(C) Distribution of m6A peaks in  Hif1a mRNA transcript in siCtrl and siFto 3T3-L1 cells. Blue boxes represent exons, and blue lines represent introns. The m6A  peaks were in the dashed red box.",
    "ncbi_link": "Fto: 26383
Hif1a: 15251"
  },
  {
    "caption": "(D) Methylated RNA immunoprecipitation  (MeRIP)-qPCR analysis of  m6A levels of Hif1a mRNA in siCtrl and siFto 3T3-L1 cells. Data information: The data were presented as the mean ± SD of triplicate tests (n = 3). Statistical analyses were performed using Student t‐test.∗∗p < 0.01, ∗∗∗p < 0.001.",
    "ncbi_link": "Fto: 26383
Hif1a: 15251"
  },
  {
    "caption": "(H) Western blot  analysis of the protein levels of HIF1A, UCP1,  PPARGC1A, PPARG and GFP  in  3T3-L1 cells infected with  lentiviruses pCDHpuro expressing Vec, WT- or MUT-HIF1A.",
    "ncbi_link": "HIF1A: 15251"
  },
  {
    "caption": "(A) Western blot analysis of the protein levels of  YTHDF1, YTHDF2  and  HIF1A in siCtrl, siYthdf1 and siYthdf2 3T3-L1  cells.",
    "ncbi_link": "Ythdf1: 228994
Ythdf2: 213541"
  },
  {
    "caption": "(G)  Polysome  profiling of 3T3-L1 cells overexpressing Vec or YTHDC2 plasmid. (H) qPCR  analysis of mRNA levels of Hif1a in  40-80S or polysome fraction in 3T3-L1  cells overexpressing Vec or YTHDC2  plasmid. (I)  Polysome  profiling  of siCtrl and siYthdc2 3T3-L1 cells. (J) qPCR analysis of mRNA levels of Hif1a in 40-80S or  polysome fraction in siCtrl and siYthdc2 3T3-L1  cells. Data information: The data were presented as the mean ± SD of triplicate tests (n = 3). Statistical analyses were performed using Student t‐test.∗∗p < 0.01, ∗∗∗p < 0.001. ",
    "ncbi_link": "Hif1a: 15251
YTHDC2: 240255
Ythdc2: 240255"
  },
  {
    "caption": "B. Western blot analysis of RAB6A/A' and RAB6B  protein levels in WT, Emx1-Cre; RAB6loxP/loxP (RAB6A  KO), RAB6B-/- (RAB6B  KO) and Emx1-Cre; RAB6AloxP/loxP; RAB6B-/- (RAB6A/B dKO) E15.5 cortical  extracts.",
    "ncbi_link": "Cre: 2777477
Emx1: 13796
RAB6A: 19346
RAB6B: 270192"
  },
  {
    "caption": "A. PAX6 staining  in WT and RAB6A/B dKO E15.5 brains. Scale bar = 50µm. B. Percentage of PAX6+ cells located in the upper half of the cortex  of WT and RAB6A/B dKO E15.5 brains. WT: 4282 cells from N=6 brains. RAB6A/B dKO: 1241 cells from N=3 brains. Mann-Whitney U test. Data information: All error bars indicate SD.",
    "ncbi_link": "RAB6A: 19346"
  },
  {
    "caption": "C. Phospho-Vimentin  (p-Vim) staining  in WT and RAB6A/B dKO E15.5 brains. Scale bar = 50µm. D. Percentage p-VIM+ cells dividing ectopically, in the upper half of the cortex  of WT and RAB6A/B dKO E15.5 brains. WT: 1713 cells from N=6 brains. RAB6A/B dKO: 506 cells from N=3 brains. Mann-Whitney U test. Data information: All error bars indicate SD.",
    "ncbi_link": "RAB6A: 19346"
  },
  {
    "caption": "G. Electroporation of  RAB6AloxP/loxP; RAB6B-/- E14.5 embryos  with mCherry  (control) or mCherry  + CRE  (RAB6A/B dKO) and live imaging of delamination events at E17.5. H. Apical endfoot detachment and retraction events during 20 hours movies in mCherry   or mCherry  + CRE  electroporated cells at E17.5. mCherry: N=69 cells from 5 movies. mCherry  + CRE: N=52 cells from 4 movies. Fisher's exact test, *p ≤ 0.05. Data information: All error bars indicate SD.",
    "ncbi_link": "mCherry: 
CRE: 2777477
RAB6A: 19346
RAB6B: 270192"
  },
  {
    "caption": "A. Localization  of the Golgi apparatus  (ManII-GFP) and the centrosome  (𝛾-tubulin) in E15.5 mCherry-electroporated radial glial cell. The Golgi apparatus is localized  basally, away from the centrosome. Scale bar = 5µm. B. Average distance between the apical-most part of the  Golgi apparatus and the apical surface in aRG cells. N=224 cells from 3 independent brains.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "I Live imaging  of GFP-RAB6A  in control, dynarrestin-treated and CC1-p150-expressing  aRG cells at E15.5. Scale bars = 5µm. Distance = 5µm, time  = 30 seconds. J. Number of RAB6A+ vesicles  in the apical  process of DMSO  and dynarrestin-treated mouse aRG cells. K. Relative time  spent by RAB6A+ vesicles  in apical  movement phase, in DMSO  and dynarrestin-treated mouse aRG cells. L. Number of RAB6A+ vesicles  in the apical  process of mCherry  and CC1-p150-expressing  aRG cells. M. Relative time  spent by RAB6A+ vesicles  in apical  movement phase, in mCherry  and CC1-p150-expressing aRG cells. DMSO  treatment slightly affected RAB6A  dynamics, as compared to mCherry  control. Data information: (J, K, L, M) 216 vesicles  from N=11 cells for DMSO, 145 vesicles  from N=25 cells for dynarrestin, 173 vesicles  from N=17 cells for mCherry  control, 71 vesicles  from N=15 cells for CC1-p150. Mann-Whitney U test *p ≤ 0.05, **p ≤ 0.01, *** p ≤ 0.001. All boxplots: whiskers indicate min and max, boxes indicate 25th and 75th percentile, and central band indicates the median.",
    "ncbi_link": "mCherry: 
p150: 1639"
  },
  {
    "caption": "C. RUSH assay for CRB3-GFP  in control (mcherry) and dynactin-inhibited radial glial cells  (CC1-p150-dsRed), electroporated at E.15.5 and imaged at E16.5. Scale bar = 5µm. D. CRB3 localization  at the apical surface  upon release. E. Percentage of cells with 100% of CRB3  signal at the apical surface  upon release. Data information: (D, E) mCherry  (control): N= 3 brains  per timepoint  (361 cells total). CC1-p150: N=3 brains  per timepoint (2 brains  for T0) (268 cells total). Fisher's exact test and Benjamini-Hochberg procedure, *** p ≤ 0.001. All error bars indicate SD.",
    "ncbi_link": "dsRed: 
mcherry: 
mCherry: 
p150: 1639"
  },
  {
    "caption": "A. PAX6 and phospho-Histone 3 (p-H3) staining  in WT and LIS1  KO E12.5 brains. Cortices were subdivided into 5 bins of equal size along the radial axis. Scale bar = 25µm. B. Percentage of PH3+/PAX6+ cells located above the ventricular surface of WT and LIS1  KO E12.5 brains. WT: 1192 cells from N=6 brains. LIS1  KO: 589 cells from N=3 brains. Data information: (B, Mann-Whitney U test, *p ≤ 0.05. All error bars indicate SD.",
    "ncbi_link": "LIS1: 18472"
  },
  {
    "caption": "C. Phospho-Vimentin  (p-VIM) staining  in WT and LIS1  KO E12.5 brains. Scale bar = 25µm. D. Percentage p-VIM+ cells dividing ectopically, away from the  ventricular surface of WT and LIS1 KO E12.5 brains. WT: 1056 cells from N=6 brains. LIS1  KO: 879 cells from N=3 brains. Data information: D) Mann-Whitney U test, *p ≤ 0.05. All error bars indicate SD.",
    "ncbi_link": "LIS1: 18472"
  },
  {
    "caption": "A. CRB3  and PALS1 staining  in WT, RAB6A/B dKO (E15.5) and LIS1  KO (E12.5) brains. Scale bar = 25µm.",
    "ncbi_link": "LIS1: 18472
RAB6A: 19346"
  },
  {
    "caption": "B. Quantification of CRB3 staining interruptions along the ventricular boundary of WT (E12.5 and E15.5; N=13 brains), LIS1  KO (E12.5, N=4 brains)) and RAB6A/B dKO (E15.5, N=4 brains). Data information: (B, Kruskal-Wallis test with a Dunn post-hoc test and Benjamini-Hochberg procedure, *p ≤ 0.05, *** p ≤ 0.001. All error bars indicate SD.",
    "ncbi_link": "LIS1: 18472
RAB6A: 19346"
  },
  {
    "caption": "C. N-Cadherin staining  in WT, RAB6A/B dKO (E15.5) and LIS1  KO (E12.5) brains. Scale bar = 25µm.",
    "ncbi_link": "LIS1: 18472
RAB6A: 19346"
  },
  {
    "caption": "D. Quantification of N-Cadh staining  interruptions along the ventricular boundary of WT (E12.5 and E15.5; N=6 brains), LIS1  KO (E12.5, N=3 brains) and RAB6A/B dKO (E15.5, N=3 brains). Data information: D) Kruskal-Wallis test with a Dunn post-hoc test and Benjamini-Hochberg procedure, *p ≤ 0.05, *** p ≤ 0.001. All error bars indicate SD.",
    "ncbi_link": "LIS1: 18472
RAB6A: 19346"
  },
  {
    "caption": "(C-J) All panels show Drosophila 3rd instar larval eye imaginal discs with eyeless-Flippase-induced clones of cells homozygous for EMC3Δ4 labelled by the absence of  ubiGFP (green). The red channel shows ELAV, which labels the nuclei  of  photoreceptor cells. All UAS constructs were expressed under the control of GMR-GAL4. (C) Expression  of UAS-Rh1 (4C5, in blue) and (D)  Na+K+ATPase (A5-C, in blue) is strongly reduced in EMC3Δ4 homozygous mutant cells. (E) Expression of UAS-Xport-A-HA (anti-HA, in blue) and (F) UAS-fan-HA  (anti-HA, in blue) is strongly reduced in  EMC3Δ4 homozygous mutant cells. (G) Expression of UAS-rtv-HA (anti-HA, in blue) and (H) hid (anti-hid, in blue) is increased in  EMC3Δ4 homozygous mutant cells. (I-J) Normal expression of two TA proteins in EMC3Δ4 homozygous mutant cells. (I) UAS-CG8814-HA (anti-HA, in blue) is a TA protein containing a TMD of low hydrophobicity (J) UAS-Syx13-HA is a TA protein with high hydrophobicity TMD. Scale bars represent 10 μm.",
    "ncbi_link": "Flippase: 32615
EMC3: 34479
eyeless: 43812
GAL4: 855828"
  },
  {
    "caption": "(B-D) - Immunostaining  of  3rd instar   larval eye imaginal discs with eyeless-Flippase-induced clones of cells homozygous for EMC3Δ4, labelled by the absence of  ubiGFP (green) shows reduced  expression of (B) UAS-HA-Xport-A (anti-HA, in blue) but normal expression of (C) UAS-HA-Xport-A4L (anti-HA, in blue) or (D) UAS-Xport-A4L-HA (anti-HA, in blue) in EMC3  mutant homozygous cells. ELAV (red in B and C) marks photoreceptor cells and Na+K+ATPase (red in D) acts as a positive control for the presence of EMC3Δ4 homozygous mutant clones. The UAS constructs were expressed under the control of GMR-GAL4. Scale bars represent 10 μm.",
    "ncbi_link": "Flippase: 32615
EMC3: 34479
eyeless: 43812
GAL4: 855828"
  },
  {
    "caption": "(E-F) Immunostaining of mosaic adult  retina with eyeless-Flippase-induced clones of cells homozygous for EMC3e02662, labelled by the absence of RFP (red), show loss of (E) UAS-HA-Xport-A (anti-HA, in blue) in EMC3 mutant homozygous cells. (F)  Expression of UAS-HA-Xport-A4L (anti-HA, in blue) is normal in EMC3e02662 homozygous mutant clones. The rhabdomeres are stained for actin (Phalloidin, in green). Scale bars represent 10 μm.",
    "ncbi_link": "Flippase: 32615
EMC3: 34479
eyeless: 43812"
  },
  {
    "caption": "(B-D) Histograms of  flow cytometry  data monitoring the fluorescence protein ratio in the indicated U2OS cell lines for each construct. \"EMC5KO+EV\" indicates a knockout of EMC5  stably harbouring empty vector, while ''EMC5KO+EMC5\" indicates EMC5KO cells rescued by inducible re-expression of a stably integrated EMC5. (E-G) Histograms of flow cytometry data monitoring the fluorescence protein ratio in the indicated U2OS  cell lines for each construct. \"EMC6KO+EV\" indicates a knockout of EMC6 stably harbouring empty vector, while ''EMC6KO+EMC6\" indicates EMC6KO cells rescued by re-expression of a stably integrated EMC6.",
    "ncbi_link": "EMC6: 83460
EMC5: 93380"
  },
  {
    "caption": "(C-G) (C-D, F) Western-Blot  of WT and EMC6KO (6KO)  U2OS cell lines transiently transfected with the opsin-tagged constructs probed for HA. When indicated, denatured samples were treated with  PNGase  to confirm glycosylation. Glycosylated proteins shift upwards in the gel and are indicated by arrows (). (E, G) Western-Blot of WT and EMC6KO (6KO)  U2OS  cell lines transiently transfected with the  opsin-tagged constructs probed for Actin  and EMC6.",
    "ncbi_link": "opsin: 
EMC6: 83460"
  },
  {
    "caption": "(A-B)  Immunostaining of  3rd instar larval eye imaginal discs with  eyeless-Flippase-induced clones of cells homozygous for  EMC3Δ4, labelled by the absence of ubiGFP (green) show loss of (A) UAS-Xport-A-HA (anti-HA, in blue) and UAS-Rh1 (4C5, in red). (B) Expression of UAS-Xport-A4L (anti-HA, in blue) and UAS-Rh1 (4C5, in red) is observed in  EMC3Δ4 homozygous cells. The UAS constructs were expressed under the control of GMR-GAL4. Scale bars represent 10 μm.",
    "ncbi_link": "Flippase: 32615
EMC3: 34479
eyeless: 43812
GAL4: 855828"
  },
  {
    "caption": "(C-D)  Immunostaining of mosaic adult retinas with  eyeless-Flippase-induced clones of cells homozygous for  EMC3e02662, labelled by the absence of RFP (red), show loss of (C) TRP (Mab83F6, in blue) when UAS-HA-Xport-A is expressed. (D)  Expression of TRP  (Mab83F6, in blue) is observed in EMC3e02662 homozygous cells, when HA-Xport-A4L is expressed. The rhabdomeres are stained  for actin  (Phalloidin, in green). The UAS constructs were expressed under the control of Rh1-GAL4. Scale bars represent 10 μm.",
    "ncbi_link": "Flippase: 32615
EMC3: 34479
eyeless: 43812
GAL4: 855828
Rh1: 246602"
  },
  {
    "caption": "(E-G) Western blot  of fly heads labelled for  V5, TRP,  Rh1, Xport-A (Xp-A) and tubulin. (E)  Immunoblot of fly heads expressing Rh1Gal4 (driver) (left) or Rh1 TMD1-V5 (right) in  Xport-A  heterozygous (Xport-A1/TM6B) or homozygous mutant flies (Xport-A1/Xport-A1). Extracts were untreated (-) or treated (+) with  PNGase F enzyme (lanes 2, 4, 6 and 8). For Rh1Gal4, 4 fly heads were loaded per well, while for  Rh1 TMD1-V5, 8  fly heads were loaded per well. (F) Immunoblot of  fly heads expressing Rh1 TMD1-3-V5 in Xport-A heterozygous (Xport-A1/TM6B) or homozygous mutant flies (Xport-A1/Xport-A1). Extracts were untreated (-) or treated (+) with PNGase F  enzyme (lanes 2 and 4). Eight fly heads  were loaded per lane. (G) Immunoblot of fly heads expressing Rh1 TMD1-5-V5 in Xport-A heterozygote (Xport-A1/TM6B) or homozygous mutant flies (Xport-A1/Xport-A1). Extracts were untreated (-) or treated (+) with either Endo-H  (lanes 2 and 5) or PNGase F enzyme (lanes 3 and 6). Each lane contains approximately 2,5 fly heads.",
    "ncbi_link": "TM6B: 
TMD1: 
V5: 
Gal4: 855828
Rh1: 246602
Xport-A: 42373"
  },
  {
    "caption": "(B) Autophagy‐negative phenotype of the apg16Δ strain. The autophagic ability of wild‐type (TN125), apg12Δ (YNM107) and apg16Δ cells (YNM114) was measured by the alkaline phosphatase assay before (black bars) and after (white bars) nitrogen starvation for 4 h. Error bars indicate the standard deviation of three independent experiments.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "(C) Loss of viability during starvation. Wild‐type (KA311B, ○), apg12Δ (YNM101, ●) and apg16Δ cells (YNM124, ▴) were cultured in nitrogen starvation medium, and their viability was determined by phloxine B staining.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "(D) Defect in API maturation in apg16Δ cells. Transport of pro‐API to the vacuole was examined by immunoblotting with anti‐API antiserum. The positions of precursor and mature API are indicated.",
    "ncbi_link": "apg16: 855194"
  },
  {
    "caption": "(E) The Apg12p-Apg5p conjugation in apg16Δ cells. Total lysates were prepared by the NaOH/2‐mercaptoethanol extraction method from apg12Δ (YNM107) and apg12Δapg16Δ cells (YNM115), both carrying pHA‐APG12 (CEN). Western blot analysis was performed using anti‐HA antibody.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Apg16p interacts with the Apg12p-Apg5p conjugate but not with the Apg12p monomer. The apg12Δapg16Δ cells (YNM115) were transformed with high copy (2μ) plasmids encoding MycApg12p and/or HAApg16p as indicated. Total lysates were immunoprecipitated with anti‐Myc (lanes 1-4) or anti‐HA antibody (lanes 5-8) and detected by immunoblotting using anti‐Myc or anti‐HA antibody. The positions of the IgG heavy chain and κ light chain are indicated.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Apg16p interacts with the Apg12p-Apg5p conjugate but not with the Apg12p monomer. The apg12Δapg16Δ cells (YNM115) were transformed with high copy (2μ) plasmids encoding MycApg12p and/or HAApg16p as indicated. Total lysates were immunoprecipitated with anti‐Myc (lanes 1-4) or anti‐HA antibody (lanes 5-8) and detected by immunoblotting using anti‐Myc or anti‐HA antibody. The positions of the IgG heavy chain and κ light chain are indicated.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Apg16p interacts preferentially with Apg12p‐modified Apg5p. Total lysates were prepared from apg16Δ cells (YNM124) or apg12Δapg16Δ cells (YNM115) harboring both pHA‐APG5 and pMyc‐APG16 CEN plasmids. The lysates were immunoprecipitated and analyzed as described in Figure 3.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Apg16p interacts preferentially with Apg12p‐modified Apg5p. Total lysates were prepared from apg16Δcells (YNM124) or apg12Δapg16Δ cells (YNM115) harboring both pHA‐APG5 and pMyc‐APG16 CEN plasmids. The lysates were immunoprecipitated and analyzed as described in Figure 3.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "(A) PJ69‐4A cells were co‐transformed with each pGBD and pGAD plasmid as indicated. Transformants were selected on Trp− Leu− plates, and then two‐hybrid interaction (+ or −) was assessed for growth on Ade− Trp− Leu− plates.",
    "ncbi_link": "pGAD: 
pGBD: "
  },
  {
    "caption": "(B) Self‐multimerization of Apg16p in vivo. Lysates of apg16Δ cells (YNM124) transformed with pMyc‐APG16 (2μ) and/or pHA‐APG16 (2μ) were immunoprecipitated with anti‐Myc antibody and detected with anti‐HA antibody.",
    "ncbi_link": "apg16: 855194"
  },
  {
    "caption": "Apg16p mediates Apg5p assembly. Immunoprecipitation was carried out as described in Figure 3, using apg12Δ (YNM107) and apg12Δapg16Δ cells (YNM115) carrying pMyc‐APG12 (CEN) and pHA‐APG12 (CEN) (A), or pMyc‐APG12 (CEN) and pHA‐APG5 (CEN) (B). Following SDS-PAGE, immunoprecipitates were subjected to immunoblot analysis using anti‐HA or anti‐Myc antibody as indicated. A model of the Apg12p-Apg5p-Apg16p complex is illustrated in each panel. Apg16p forms a homo‐oligomer through its C‐terminal coiled‐coil region. It is not clear whether Apg16p forms a dimer or a larger multimer. The N‐terminal region of each Apg16p interacts with Apg5p; most of these complexes are conjugated to Apg12p (A) but a small population are unmodified (B). In the absence of Apg16p, separate Apg5ps do not assemble.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Apg16p mediates Apg5p assembly. Immunoprecipitation was carried out as described in Figure 3, using apg12Δ (YNM107) and apg12Δapg16Δ cells (YNM115) carrying pMyc‐APG12 (CEN) and pHA‐APG5 (CEN) (B). Following SDS-PAGE, immunoprecipitates were subjected to immunoblot analysis using anti‐HA or anti‐Myc antibody as indicated. A model of the Apg12p-Apg5p-Apg16p complex is illustrated in each panel. Apg16p forms a homo‐oligomer through its C‐terminal coiled‐coil region. It is not clear whether Apg16p forms a dimer or a larger multimer. The N‐terminal region of each Apg16p interacts with Apg5p; most of these complexes are conjugated to Apg12p (A) but a small population are unmodified (B). In the absence of Apg16p, separate Apg5ps do not assemble.",
    "ncbi_link": "apg12: 852518
apg16: 855194"
  },
  {
    "caption": "Expression levels of Apg16p are dependent on the Apg12p-Apg5p conjugate. Total lysates were prepared by the NaOH/2‐mercaptoethanol extraction method from apg16Δ (YNM124), apg5Δapg16Δ (YNM126) and apg12Δapg16Δ cells (YNM115) carrying pHA‐APG16 (CEN). Western blot analysis was performed using anti‐HA antibody.",
    "ncbi_link": "apg12: 852518
apg16: 855194
apg5: 855954"
  },
  {
    "caption": "Expression levels of Apg16p are dependent on the Apg12p-Apg5p conjugate. Total lysates were prepared by the NaOH/2‐mercaptoethanol extraction method from apg16Δ (YNM124), apg5Δapg16Δ (YNM126) and apg12Δapg16Δ cells (YNM115) carrying pHA‐APG16 (CEN). Western blot analysis was performed using anti‐HA antibody.",
    "ncbi_link": "apg12: 852518
apg16: 855194
apg5: 855954"
  },
  {
    "caption": "Apg16p exists in a pellet fraction in an Apg5p‐dependent manner. Spheroplasts were generated from cells harboring pHA‐APG5 (A), pHA‐APG16 (B) or pHA‐APG16 (2μ) with or without pHA‐APG5 (2μ) (C). They were lysed by Dounce homogenization. After unbroken spheroplasts were removed by low‐speed centrifugation, the supernatant (T) was fractionated by 100 000 g centrifugation for 60 min to generate a supernatant (S) and pellet (P) fraction. Each fraction was subjected to immunoblot analysis using anti‐HA antibody.",
    "ncbi_link": "APG16: 855194
APG5: 855954"
  },
  {
    "caption": "(A) IDH1 acetylation levels upon treatment with NAM or TSA. Flag-tagged IDH1 was ectopically expressed in HEK293T cells treated with NAM (5 mM) and/or TSA (0.5 mM) for the indicated time period.",
    "ncbi_link": "Flag: 
IDH1: 3417"
  },
  {
    "caption": "(C) Mutation of IDH1 K224R and K224Q resulted in altered acetylation levels using Western Blot.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(D) IDH1 catalytic activity of IDH1 K224 mutants in vitro. Wild-type IDH1 and K224R, K224Q mutants were expressed in HEK293 cells. Proteins were purified by immunoprecipitation (IP), IDH1 levels were normalized for protein, and activity assays were performed. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For multiple comparisons in (D), a one-way ANOVA with Newman-Keuls post hoc test was used to test for statistical significance.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(E-F) Steady-state kinetic analysis of IDH1 and variants in HEK293T cells. Comparison of IDH1 WT and K224R and K224Q showed that the K224 site was important in catalysis. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For (E-F), statistical significance was determined using the two-way ANOVA followed by Tukey's post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(G) IDH1 directly interacted with SIRT2 but not SIRT1. SIRT2 deacetylated IDH1 effectively. Flag tagged IDH1 and HA tagged SIRT1 or SIRT2 were co-transfected into cells. The acetylation level of Flag-bead-purified IDH1 and the protein association between IDH1 and SIRT1 or SIRT2 were determined by Western blot.",
    "ncbi_link": "Flag: 
HA: 
IDH1: 3417
SIRT1: 23411
SIRT2: 22933"
  },
  {
    "caption": "(K) IDH1 K224 deacetylation was dependent on SIRT2 catalytic activity. SIRT2 H187Y was a catalytically inactive mutant.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(A) Colony formation ability after transfection of SIRT2 plasmids, AGK2 and SIRT2 siRNA. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For A statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(B) Transwell assay was performed to evaluate the invasion abilities of HCT116 cells after overexpression or downregulation of SIRT2 or treated with AGK2. Stained cells in the lower chambers were quantified. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(D) Cell cycle distribution was evaluated flow cytometrically after treatment with SIRT2 plasmids, SIRT2 siRNA or AGK2. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For D, statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "SIRT2: 22933"
  },
  {
    "caption": "(A-B) IDH1 K224 acetylation level was enhanced with increasing glucose concentration. Flag-IDH1 was overexpressed in cells treated with increased concentrations of glucose for 6 h. IDH1 proteins were purified by Flag beads, and then IDH1 K224 acetylation level was determined by Western blot and IDH1 catalytic activity was assessed. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For B statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "Flag: 
IDH1: 3417"
  },
  {
    "caption": "(C-D) IDH1 K224 acetylation level was upregulated and IDH1 activity was weakened with increasing glutamine concentration. Flag-IDH1 was overexpressed in cells treated with increased glutamine for 6 h. IDH1 proteins were purified by Flag beads, and the K224 acetylation level of IDH1 was determined by Western blot analysis and then IDH1 catalytic activity was evaluated. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For , D statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "Flag: 
IDH1: 3417"
  },
  {
    "caption": "Downregulation of SIRT2 diminished the effect of glucose on changing IDH1 K224 acetylation. Flag-tagged IDH1 was overexpressed in HCT116 cells with or without transient SIRT2 knockdown. The cells were treated with different concentrations of glucose (E)",
    "ncbi_link": "Flag: 
IDH1: 3417
SIRT2: 22933"
  },
  {
    "caption": "Downregulation of SIRT2 diminished the effect of glutamine on changing IDH1 K224 acetylation. Flag-tagged IDH1 was overexpressed in HCT116 cells with or without transient SIRT2 knockdown. The cells were treated with different concentrations of glutamine (F).",
    "ncbi_link": "Flag: 
IDH1: 3417
SIRT2: 22933"
  },
  {
    "caption": "(G) IDH1 K224 deacetylation regulated cellular NADPH/NADP+ redox in cells. In HCT116 stable cells with IDH1 knockout and re-expressing the indicated proteins, the ratio of NADPH/NADP+ in cells was measured as followed by manufacture's instruction. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For , G statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(H) IDH1 K224 deacetylation promoted GSH production in HCT116 cells. In HCT116 stable cells with IDH1 knockout and re-expressing the indicated proteins, the ratio of GSH/GSSG was assessed as followed by manufacture's instruction. 1 Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For H, statistical significance was assessed with the one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(I) IDH1 K224 deacetylation suppressed cellular ROS levels in HCT116 cells. ROS was determined in cells under non-stressed condition or exposed to menadione. *P<0.05 and **P<0.01 Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For figure I, statistical significance was assessed with the two-way ANOVA followed by Tukey's post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(A) Gene expression profile array analysis in HCT116 cells. Representative genes with higher fold difference (up or down) compared IDH1 K224R cells with IDH1 WT cells. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition).",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(B) ChIP assays for HIF1α and its binding motif. Antibodies anti-IgG and anti- HIF1α were used in the ChIP assays. qRT-PCR was performed to quantify the binding activity. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For B , statistical significance was assessed with a two-tailed unpaired Student's t-test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "HIF1α: 3091"
  },
  {
    "caption": "(C-D) The transcriptional activity of the SRC promoter was greatly increased after co-expression of HIF1α and SRC reporter in wild type. SRC promoter constructs containing a potential HIF1α binding motif (-1636~-1629 bp and -1466~-1459 bp). Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For D, statistical significance was assessed with a two-tailed unpaired Student's t-test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "HIF1α: 3091
SRC: 6714"
  },
  {
    "caption": "(E) IDH1 K224 deacetylation led to degradation of HIF1α but upregulation of hydroxy-HIF1α. In HCT116 stable cells with IDH1 knockout and re-expressing the indicated proteins, HIF1α and hydroxy-HIF1α was measured by Western blot assay.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(F) HCT116 cells of IDH1 K224Q were cotreated with Octyl-α-KG and NAC, the expression of HIF1α and SRC was further evaluated.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "HCT116 cells expression IDH1 K224Q with or without treatment with Octyl-α-KG and/or NAC were analyzed for glucose levels. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For G statistical significance was assessed with a one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "HCT116 cells expression IDH1 K224Q with or without treatment with Octyl-α-KG and/or NAC were analyzed for lactate levels. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For H, statistical significance was assessed with a one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01. n.s. = not significant.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(A) Transwell assay was performed to evaluate the invasion abilities of HCT116 cells after transfection of IDH1 K224R or knockout of IDH1. Quantification was performed by counting the stained cells that invaded to the lower chamber under a light microscopy. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For A statistical significance was assessed with a one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(D) Colony formation ability after deacetylation of IDH1 K224 or knockout of IDH1. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For statistical significance was assessed with a one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(E) Cell cycle distribution was assessed flow cytometrically after treatment with IDH1 K224R or knockout of IDH1. Data information: All results were expressed as mean ± SD of three independent experiments (n ≥ 3 per experimental condition). For E, statistical significance was assessed with a one-way ANOVA with Newman-Keuls post hoc test. *P<0.05 and **P<0.01.",
    "ncbi_link": "IDH1: 3417"
  },
  {
    "caption": "(A) Murine Ntras  enrichment in endothelial cells versus other heart-derived cell types (data acquired from GSE95755 (n = 4 mice). Data information: In (A, data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (A) One-way ANOVA",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(B) Changes in lncRNA expression  from HUVECs  exposed to hypoxia   (0.2 %  O2 for 12 h or 24 h), determined by ribo-minus RNA deep sequencing  (data acquired from GSE107033 ; NTRAS  is highlighted (n = 2 independent biological replicates).",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(C) Validation of hypoxia-induced NTRAS expression  at the indicated time points by RT-qPCR  (n = 4 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. two-tailed unpaired t-test",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(D) Subcellular localization  of NTRAS  and control transcripts, assayed by nuclear-cytoplasmic  fractionation of HUVECs and RT-qPCR (n = 3 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. two-tailed unpaired t-test",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(E) FITC-dextran-based in vitro permeability  comparing control and NTRAS-silenced HUVECs  (n = 5 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. two-tailed unpaired t-test,",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(F) Cumulative in vitro sprout  lengths of control and NTRAS-silenced HUVECs  under basal conditions and VEGFA  stimulation (n = 3-10 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(G) Cell cycle analysis in Ntras-silenced H5V cells (n = 3 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (G) two-way ANOVA,",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(H) TMR-dextran-based assessment of vascular  permeability in vivo, comparing heart  homogenates from control and Ntras-silenced mice. Data normalized to organ and body weight (n = 11-12 mice  per group). Experimental outline on the left. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. H) two-tailed unpaired t-test",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(I) Survival  of control and Ntras-silenced mice under basal conditions (black, n = 21-23 mice  per group) and in hind limb ischemia (HLI; red, n = 8 mice  per group). Number of survivors is indicated; experimental outline on the left. Data information: (I) Mantel-Cox-test.",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(A) Separation of mock and proteinase K-treated HeLa nuclear  extracts by  sucrose  density gradient ultracentrifugation followed by NTRAS  detection using  RT-qPCR. Fractions 1 and 14 represent top and bottom of the gradient, respectively (n = 1).",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(B) Enrichment of NTRAS  by  antisense affinity selection  from HeLa  cell lysate followed by  RT-qPCR, comparing a control and an NTRAS-specific probe (n = 5 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. two-tailed unpaired t-test.",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(D) RT-qPCR-based validation of NTRAS-hnRNPL-interaction  by anti-hnRNPL RIPs  from HUVEC nuclear  fractions (n = 6 independent biological replicates). Representative  western blot  on the right. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. two-tailed unpaired t-test.",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(E)  RT-qPCR analysis of NTRAS expression   in HUVECs  upon silencing of hnRNPL (n = 4 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. two-tailed unpaired t-test.",
    "ncbi_link": "hnRNPL: 3191
NTRAS: 257194"
  },
  {
    "caption": "(F) RPLP0-normalized NTRAS-CA16 motif expression  after hnRNPL  silencing determined by  RT-PCR (n = 4 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. two-tailed unpaired t-test.",
    "ncbi_link": "hnRNPL: 3191
NTRAS: 257194
RPLP0: 6175"
  },
  {
    "caption": "(H) NTRAS  and hnRNPL  co-regulated alternative splicing  (AS) events. Data points with an FDR < 0.05 are circled (n = 2 independent biological replicates).",
    "ncbi_link": "hnRNPL: 3191
NTRAS: 257194"
  },
  {
    "caption": "(I) RT-PCR-based analysis of  TJP1 exon 20 inclusion  upon silencing of NTRAS  in HUVECs  (n = 7 independent biological replicates). Representative agarose  gels on the right. Data information: , I, data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. I, two-tailed unpaired t-test.",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(J) RT-PCR-based analysis of TJP1 exon 20 inclusion upon silencing of hnRNPL  in HUVECs  (n = 4 independent biological replicates). Representative agarose  gels on the right. Data information: , J) data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, ***p < 0.001. J) two-tailed unpaired t-test.",
    "ncbi_link": "hnRNPL: 3191
TJP1: 7082"
  },
  {
    "caption": "(B) In vitro splicing  efficiency of the TJP1  splice substrate, comparing mock, NTRAS-depleted, and NTRAS-CA16 motif add-back conditions (n = 7-12 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. (B two-tailed unpaired t-test,",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(C) Co-precipitation of TJP1  pre-mRNA in anti-hnRNPL RIPs, using nuclear  lysates from control and NTRAS-silenced HUVECs  (n = 6 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed paired t-test",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(D) Co-precipitation of TJP1  pre-mRNA in anti-hnRNPL RIPs, using nuclear  lysates from control and NTRAS-overexpressing cells (n = 5 independent biological replicates). Representative western blot  on the right. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed paired t-test,",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(E) Co-precipitation of TJP1  pre-mRNA in anti-hnRNPL RIPs, using nuclear  lysates from control and NTRAS-CA16 motif overexpressing cells (n = 5 independent biological replicates). Representative western blot on the right. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed paired t-test,",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(F) RT-PCR-based analysis of TJP1 exon 20 inclusion upon NTRAS  overexpression and overexpression of the NTRAS-CA16 motif (n = 8 independent biological replicates). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. one-way ANOVA.",
    "ncbi_link": "NTRAS: 257194
TJP1: 7082"
  },
  {
    "caption": "(G) Endothelial   resistance of NTRAS-silenced HUVECs  (n = 3-5 independent biological replicates), analyzed by electrical cell-substrate impedance sensing (ECIS). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed unpaired t-test",
    "ncbi_link": "NTRAS: 257194"
  },
  {
    "caption": "(H) Endothelial  resistance of hnRNPL-silenced HUVECs  (n = 3 independent biological replicates), analyzed by ECIS. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed unpaired t-test,",
    "ncbi_link": "hnRNPL: 3191"
  },
  {
    "caption": "(I) Analysis of TJP1 exon 20 inclusion by RT-PCR  upon transfection of HUVECs  with a control SSO or an SSO masking the exon 20 - intron 20 boundary (E20  SSO) (n = 9 independent biological replicates). Representative agarose  gel on the right. Schematic outline at the top right. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01. two-tailed unpaired t-test,",
    "ncbi_link": "TJP1: 7082"
  },
  {
    "caption": "(A) Validation of Ntras-hnRNPL-interaction  by anti-hnRNPL RIPs  from H5V lysates, followed by RT-qPCR  (n = 4 independent biological replicates). Representative western blot on the right. Data information: In (A, data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. (A) two-tailed paired t-test",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(B)  RT-PCR-based analysis of murine Tjp1 exon 20 inclusion in cardiac  tissue from control and Ntras-silenced mice  (n = 8 mice  per group). Experimental outline on the left. Data information: In data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. (B, two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840
Tjp1: 21872"
  },
  {
    "caption": "(D) Co-precipitation of Ntras  in anti-hnRNPL RIPs  using whole heart  lysates from NtrasCA/CA and Ntras∆CA/∆CA mice  (n = 3-4 mice  per group). Representative  western blot  on the right. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(E) RT-PCR-based analysis of TJP1 exon 20 inclusion in hearts  from NtrasCA/CA and Ntras∆CA/∆CA mice  (n = 9-14 mice  per group). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840
TJP1: 21872"
  },
  {
    "caption": "(F) Retinal  angiogenesis  assessed in P7 NtrasCA/CA and Ntras∆CA/∆CA pups  by immunostaining  of isolectin B4. Vascularized areas were normalized to total retinal  area (n = 4-8 mice  per group). Representative micrographs  are shown. Scale bars are 200 µm. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(G) FTSC  and TMR-dextran in vivo permeability  assays, comparing homogenates of hearts from NtrasCA/CA and Ntras∆CA/∆CA mice. Data normalized to organ and body weight (n = 11-18 mice  per group). Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(H) Quantification of CD45+ cell (red) infiltration into cardiac  tissue from NtrasCA/CA and Ntras∆CA/∆CA mice  normalized to DAPI.  Isolectin B4 (green) was used to label endothelial cells  (n = 4-5 mice  per group). Representative micrographs  are shown. Scale bars are 50 µm. Insets and arrows indicate sites of CD45+ cell infiltration. Data information: data are represented as mean ± S.E.M. n.s.: non-significant, *p < 0.05, **p < 0.01, ***p < 0.001. two-tailed unpaired t-test,",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "(I) Percentage of control and Ntras-silenced mice  showing cardiac pathologies  (n = 15-17 mice  per group). Prevalence is indicated above the bars. H&E micrographs  of murine heart  sections from control and Ntras-silenced mice  are shown. Insets and arrows indicate sites of lymphocytic  infiltration. Scale bars are 100 µm. Data information: (I) Chi-square test.",
    "ncbi_link": "Ntras: 320840"
  },
  {
    "caption": "Plasma corticosterone levels at baseline, 30 minutes after induction of stress by placing mice in a clean cage, and after 90 minutes upon return in the home cage. DEX mice received an injection of dexamethasone at 0.1 mg/kg body weight 150 minutes before collecting the first blood sample (n = 5-6 animals per group). Flox and GRBATKO mice were injected with 0.02 mg/kg dexamethasone and the procedure described in (A) was followed to induce stress in order to detect potential differences between Flox and GRBATKO mice which could have been obscured by the higher concentration used in (A) (n = 6-7 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GR mRNA levels in BAT of Flox and GRBATKO mice. Organs were harvested in the stressed condition after placing mice for 30 minutes in a clean cage. Half of the animals received a dexamethasone injection 180 minutes before onset of the procedure, controls received an injection with saline (n = 5-6 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Serum corticosterone levels under stressed conditions in Flox and GRBATKO mice (n = 5-6 animals per group). Blood glucose levels (n = 5-6 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Knockdown of GR in BAT assessed by immunoblotting. Β-Tubulin was used as loading control. Quantification of immunoblot in (A) using Image Lab (n = 6 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Representative Hematoxilin and eosin staining image of BAT of cold-exposed Flox and GRBATKO mice. Scale bar 50 µm.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Triglyceride content in BAT from Flox and GRBATKO animals (n = 5-6 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Heatmap of mean gene expression fold changes in thermogenic marker genes based on BAT microarray analysis comparing GRBATKO vs Flox control animals, indicating unchanged thermogenic marker gene expression. Color gradient ranges from 2-fold higher expression in GRBATKO over Flox controls (red) to 0.1-fold (lower) expression (blue) (n = 4 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Serum NEFA and triglycerides concentration in Flox and GRBATKO mice after fasting and refeeding (n = 6 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Total oxygen consumption plotted against body weight indicating that lower energy expenditure in GRBATKO animals is independent of body weight (n = 6-8 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Body weight in Flox and GRBATKO after 24 weeks of high-fat feeding (n = 10-13 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "BAT and iWAT weight in Flox and GRBATKO mice fed HFD for 24 weeks (n = 10-13 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "GR levels in BAT after 24 weeks high-fat feeding (n=10-13 mice per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Representative H&E stained sections of BAT from Flox and GRBATKO animals. Scale bar 100 µm.",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "qRT-PCR analysis of thermogenic marker gene expression in BAT of Flox and GRBATKO mice after high-fat feeding (n = 9-13 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "Blood glucose in Flox and GRBATKO animals after 24 weeks HFD (n = 10-13 animals per group).",
    "ncbi_link": "GR: 14815"
  },
  {
    "caption": "A. Spinning disk time-lapse microscopy of WT and UBAP2L KO HeLa cells synchronized with double thymidine block and release (DTBR) in mitosis. The selected frames of the movies are depicted and the corresponding time is indicated in minutes. SiR-DNA was used for DNA staining.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "I, J. The time of mitotic entry (I) and from prophase to anaphase (J) was quantified. At least 50 cells per condition were analyzed for each experiment (n=3). Red bars represent the mean. K-M. The percentages of cells with abnormal mitosis (chromosome misalignments and/or DNA bridges) (K), polylobed or multinucleated daughter cells (L) and mitotic cell death (M) were quantified. At least 50 cells per condition were analyzed. N. The nuclear size of at least 1000 control and UBAP2L-downregulated interphasic cells was measured. Red bars represent the mean.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "A-C. Immunofluorescence (IF) representative pictures of WT or UBAP2L KO cells synchronized in G1/S with DTB or in early mitosis with DTBR (A) and quantification of the percentage of cells with normal (2) or abnormal number of centrosomes in interphase (B) or in early mitosis (C). At least 50 cells per condition were analyzed for each experiment. Graphs represent the mean of three biological replicates ± SD (two sample two-tailed t-test ns=non-significant).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "D-F. IF representative pictures of HeLa cells transfected with siCTL or siUBAP2L for 48h and synchronized in G1/S with DTB or in early mitosis with DTBR (D) and quantification of the percentage of cells with normal (2) or abnormal number of centrosomes in interphase (E) or in early mitosis (F). At least 50 cells per condition were analyzed for each experiment. Graphs represent the mean of three biological replicates ± SD (two sample two-tailed t-test ns=non-significant).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "G, H. IF representative pictures of WT or UBAP2L KO cells synchronized in mitosis with DTBR (G) and quantification of the percentage of cells with bipolar or non-bipolar mitotic spindle (H). At least 50 cells per condition were analyzed for each experiment. The graph represents the mean of three biological replicates ± SD (two sample two-tailed t-test ns=non-significant).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "D. WB analysis of WT or UBAP2L KO HeLa cell lysates from G1/S synchronized cells using DTB. Proteins MW is indicated in kDa. WB is representative of three independent replicates.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "E, F. IF representative pictures of G1/S synchronized WT or UBAP2L KO HeLa cells using DTB and quantification of PLK1 nuclear intensity (A.U.) ROIs are shown in the corresponding numbered panels. Scale bar, 5µm. At least 250 cells were quantified per condition for each replicate. Each dot of graphs (F) represents PLK1 nuclear intensity in a single nucleus where PLK1 signal was detectable. Interphasic cells which do not express PLK1 were excluded from the quantification. The measurements of four biological replicates are combined, red bars represent the mean (Kruskal-Wallis test with Dunn's correction **P<0,01, ****P<0,0001).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "B. WB analysis of control or UBAP2L-silenced HeLa lysates from mitotic cells synchronized with 1µM paclitaxel and treated with 100µg/mL CHX for the indicated times. Proteins MW is indicated in kDa. WB is representative of three independent replicates.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "C. WB analysis of WT or UBAP2L KO HeLa lysates from G1/S synchronized (DTB) cells treated with 25µM of the proteasomal inhibitor MG132 for the indicated times. Proteins MW is indicated in kDa. WB is representative of three independent replicates.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "D. Representative IF pictures of WT or UBAP2L KO HeLa cells synchronized in G1/S using DTB, in S using 2mM hydroxyurea (HU) for 20h or in G2 using 10µM of CDK1 inhibitor RO 3306 for 20h.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "IF analysis of G1/S synchronized WT or UBAP2L KO HeLa cells using DTB and transfected with the indicated flag-tagged UBAP2L protein fragments for 48h (A) Scale bar, 5µm. At least 100 cells per condition were quantified for each experiment. Graphs represent the mean of three replicates ± SD (one-way ANOVA with Sidak's correction *P<0,05, **P<0,01, ns=non-significant).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "IF representative pictures of WT or UBAP2L KO HeLa cells transfected with the indicated flag-tagged UBAP2L protein fragments for 48h and synchronized in mitosis using monastrol release (MR) (C) Scale bar, 5µm. At least 50 cells per condition were quantified for each experiment.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "Colony formation assay of WT or UBAP2L KO HeLa cells transiently transfected with the indicated flag-tagged UBAP2L protein fragments after 7 days of culture. Graphs represent the mean of three replicates ± SD (one-way ANOVA with Sidak's correction *P<0,05, ****P<0,0001, ns=non-significant).",
    "ncbi_link": "flag: 
UBAP2L: 9898"
  },
  {
    "caption": "Representative IF images of WT or UBAP2L KO HeLa cells synchronized in G1/S using DTB and transfected with the indicated flag-tagged UBAP2L constructs and control or G3BP1/2 siRNAs for 48h (A)",
    "ncbi_link": "flag: 
G3BP1: 10146
UBAP2L: 9898"
  },
  {
    "caption": "Representative IF images of WT or UBAP2L KO HeLa cells synchronized in G1/S using DTB and treated with vehicle (DMSO) or 25µM of MG132 for 4h (C)",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "Representative IF images of control or UBAP2L-downregulated cells synchronized in prometaphase using 1mM monastrol and released at the indicated time points.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "E. Spinning disk time-lapse microscopy of PLK1-eGFP Knock-In (KI) HeLa cells synchronized with DTBR in mitosis. The selected frames of the movies are depicted and the corresponding time is indicated in minutes. SiR-DNA was used for DNA staining.",
    "ncbi_link": "eGFP: 
PLK1: 5347"
  },
  {
    "caption": "A, B. Representative IF pictures of WT or UBAP2L KO HeLa cells synchronized in mitosis with DTBR (A) and quantification of the relative PLK1 intensity at the inner centromere (A.U.) (B). ROIs are shown in the corresponding numbered panels. Scale bar, 5µm. At least 50 cells were quantified per condition for each experiment. Each dot represents PLK1/INCENP intensity ratio at a single centromere. The measurements of three biological replicates are combined, red bars represent the mean (Mann-Whitney test ****P<0,0001).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "C, D. Representative IF pictures of WT or UBAP2L KO HeLa cells synchronized in mitosis with DTBR (C) and quantification of the relative PLK1 intensity at the centrosomes (A.U.) (D). ROIs are shown in the corresponding numbered panels. Scale bar, 5µm. At least 50 cells were quantified per condition for each experiment. Each dot represents PLK1/Pericentrin intensity ratio at a single centrosome. The measurements of three biological replicates are combined, red bars represent the mean (Mann-Whitney test ****P<0,0001).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "E, F. Representative IF pictures of WT or UBAP2L KO HeLa cells synchronized in mitosis with DTBR (E) and quantification of the relative PLK1 intensity at the midbody (A.U.) (F). ROIs are shown in the corresponding numbered panels. Scale bar, 4µm. At least 50 cells were quantified per condition for each experiment. Each dot represents PLK1/PRC1 intensity ratio at the midbody. The measurements of three biological replicates are combined, red bars represent the mean (Mann-Whitney test **P<0,01).",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "G. Representative IF pictures of WT or UBAP2L KO HeLa cells synchronized in mitosis with DTBR (n=3) to qualitatively assess the localization of PLK1 at the mitotic spindle with α-tubulin staining. ROIs are shown in the corresponding numbered panels. Scale bar, 5µm.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "D. WB analysis of control (siCTL) or siUBAP2L 48h-treated HeLa cells were synchronized with 1mM monastrol for 16h, treated with DMSO or with 10nM of the PLK1 inhibitor BI2536 for 45min, subsequently washed out from monastrol for the indicated time and collected for protein extraction. This moderate treatment is sufficient to restore the aberrant PLK1 catalytic activity observed in UBAP2L KO cells to the levels of the WT, enabling correct mitotic progression but prevents control cells to progress through mitosis. Proteins MW is indicated in kDa. WB is representative of three independent replicates.",
    "ncbi_link": "UBAP2L: 9898"
  },
  {
    "caption": "A) Image of 8-9 day old male control (w1118, left) and chmRNAi (right) flies  upon ubiquitous chm  knockdown (left) and the corresponding quantification (right) (N = 6, Paired t-test was performed for statistical significance); B) Image of 8-9 day old male control (w1118, left) and chmRNAi (right) flies  upon fat-body  specific chm  knockdown (left) and the corresponding quantification (right) (N = 4, Paired t-test was performed for statistical significance); C) Image of 8-9 day old male control (w1118, left) and chmRNAi (right) flies  upon neuron  specific chm  knockdown (left) and the corresponding quantification (right) (N = 3, Paired t-test was performed for statistical significance); D) Image of 8-9 day old male control (w1118, left) and chmRNAi (right) flies  upon muscle  specific chm  knockdown (left) and the corresponding quantification (right) (N = 3, Paired t-test was performed for statistical significance) Data information: All replicates are independent biological replicates and errors bars indicate standard error of the mean (SEM). Paired t-test or Tukey test was performed as indicated and non-significant values are not shown (* - p < 0.05, ** - p < 0.01, *** - p < 0.001, **** - p < 0.0001).",
    "ncbi_link": "chm: 43928"
  },
  {
    "caption": "A) Heatmap showing all significant proteins (FDR < 0.05 and Π < 0.05) between control (w1118) and  chmRNAi. Values in the heatmap are scaled raw intensity values. NAs are indicated in grey;",
    "ncbi_link": "chm: 43928"
  },
  {
    "caption": "A) Average  survival curve of control (w1118) and chmRNAi male flies  upon ubiquitous knockdown of chm  with da-Gal4  (N = 4, paired , Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001)); B) Average survival curve of control (w1118) and chmRNAi male flies  upon fatbody  knockdown of chm  with r4-Gal4  (N = 4, paired , Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001)); C) Average survival curve  of control (w1118) and chmRNAi male flies  upon neuronal  knockdown of chm  with elav-Gal4  (N = 4, paired , Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001)); D) Average survival curve of control (w1118) and chmRNAi male flies  upon muscle  knockdown of chm  with mef-Gal4  (N = 4, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001)); E, F Average survival curve  between E) ethanol  (N = 3, paired Log-rank test was performed for each biological replicate. p-values ranged between 0.2 to 0.05 across replicates) and F) RU486  (N = 4, paired, Log-rank test was performed for each biological replicate with all of them having a p-value < 0.05)) and administered control (w1118) and chmRNAi male flies  using Act-GS-Gal4  for adult-specific chm  knockdown; G) Average survival curve  of control (w1118) and chmMYST/+ male flies  (N = 5, paired Log-rank test was performed for each biological replicate with all of them having a p-value < 0.0001). Data information: All replicates are independent biological replicates and errors bars indicate standard error of the mean (SEM). For survival curves, log-rank test was performed for each biological replicate. The displayed p-value is based on all biological replicates.",
    "ncbi_link": "Act: 31521
chm: 43928
da: 34413
elav: 31000
Gal4: 855828
mef: 36032"
  },
  {
    "caption": "A) Weight  of 8-9 day old male chmMYST/+ and chmMYST/+;UAS-chmmyc flies  upon weak (left, N = 5, paired) and strong (right, N = 4, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001) chm  overexpression with arm-Gal4 and da-Gal4  respectively (Paired t-test was performed); Data information: All are independent biological replicates and errors bars indicate standard error of the mean (SEM). Paired t-test was performed for the fly weight data and non-significant values are not shown (* - p < 0.05, ** - p < 0.01, *** - p < 0.001, **** - p < 0.0001).",
    "ncbi_link": "myc: 
arm: 31151
chm: 43928
da: 34413
Gal4: 855828"
  },
  {
    "caption": "B) Average survival curve of  chmMYST/+ and chmMYST/+;UAS-chmmyc male flies  upon ubiquitous weak expression of chm   with arm-Gal4  (N = 4, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001); C) Average survival curve  of chmMYST/+ and chmMYST/+;UAS-chmmyc male flies  upon ubiquitous strong expression of chm   with da-Gal4  (N = 3, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001); Data information: All are independent biological replicates and errors bars indicate standard error of the mean (SEM). For  survival curves, log-rank test was performed for each biological replicate. The displayed indicated p-value is based on all biological replicates. ",
    "ncbi_link": "myc: 
arm: 31151
chm: 43928
da: 34413
Gal4: 855828"
  },
  {
    "caption": "D) Average survival curve of chmMYST/+ and chmMYST/+;UAS-chmmyc male flies  upon fatbody  expression of chm   with r4-Gal4  (N = 4, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001); E) Average  survival curve  of control  chmMYST/+ and chmMYST/+;UAS-chmmyc  male flies  upon neuronal   expression of chm   with elav-Gal4  (N = 5, paired, Log-rank test was performed for each biological replicate. All replicates had p-values < 0.0001); F) Average survival curve of  chmMYST/+ and  chmMYST/+;UAS-chmmyc male flies  upon muscle  expression of chm   with mef-Gal4  (N = 5, paired, Log-rank test was performed for each biological replicate. p-values ranged between 0.6 to 0.0001 across replicates). Data information: All are independent biological replicates and errors bars indicate standard error of the mean (SEM). For  survival curves, log-rank test was performed for each biological replicate. The displayed indicated p-value is based on all biological replicates. ",
    "ncbi_link": "myc: 
chm: 43928
elav: 31000
Gal4: 855828
mef: 36032"
  },
  {
    "caption": "(A qRT-PCR for different ISGs relative to Rps29 using epidermal RNA from 8 week-old (A) K5-R1/R2 and control (CTRL) mice.",
    "ncbi_link": "Rps29: 20090"
  },
  {
    "caption": "qRT-PCR for different ISGs relative to Rps29 using epidermal RNA from 5 day- or 9 day-old (B) K5-R1/R2 and control (CTRL) mice.",
    "ncbi_link": "Rps29: 20090"
  },
  {
    "caption": "(D) qRT-PCR for different ISGs, Ifnb, and Ifnl3 relative to Rps29 using RNA from freshly isolated, non-cultured keratinocytes of K5-R1/R2 and control (CTRL) mice at P7.",
    "ncbi_link": "Ifnb: 15977
Ifnl3: 338374
Rps29: 20090"
  },
  {
    "caption": "(E) qRT-PCR for ISGs relative to Rps29 using RNA from primary keratinocytes of neonatal CTRL and K5-R1/R2 mice.",
    "ncbi_link": "Rps29: 20090"
  },
  {
    "caption": "(F) qRT-PCR for ISGs and Cre relative to Rps29 using RNA from primary keratinocytes of neonatal K5-Cre and wild-type (WT) mice.",
    "ncbi_link": "Cre: 2777477
Rps29: 20090"
  },
  {
    "caption": "(H) qRT-PCR for RSAD2 and ISG15 relative to RPLP0 using RNA from HaCaT keratinocytes treated for 48 h with the FGFR inhibitor BGJ398 (3.5 μM) or vehicle in the presence of serum.",
    "ncbi_link": "RPLP0: 
ISG15: 9636
RSAD2: 91543"
  },
  {
    "caption": "(A) Growth factor-starved primary keratinocytes from WT mice were treated for 3 or 6 h with FGF7 (10 ng/ml) or vehicle (CTRL). RNA samples were analyzed by qRT-PCR for the indicated ISGs relative to Rps29.",
    "ncbi_link": "Rps29: 20090"
  },
  {
    "caption": "(B) Serum-starved HaCaT keratinocytes were treated for 6 h with FGF7 or FGF10 (each 10 ng/ml). RNA samples were analyzed by qRT-PCR for IRF7 and RSAD2 relative to RPLP0.",
    "ncbi_link": "RPLP0: 
IRF7: 3665
RSAD2: 91543"
  },
  {
    "caption": "(D) RNA samples from untreated, serum-starved primary keratinocytes from WT and Ifnar1-KO mice were analyzed by qRT-PCR for Irf7, Rsad2, Oasl2 and Ifnar1 relative to Rps29.",
    "ncbi_link": "Ifnar1: 15975
Irf7: 54123
Oasl2: 23962
Rps29: 20090
Rsad2: 58185"
  },
  {
    "caption": "(E) Growth factor-starved primary keratinocytes from neonatal WT, Ifnar1-KO or Ifnar1/Ifnlr1-KO mice were treated for 24 h with FGF7 (10 ng/ml). RNA samples were analyzed by qRT-PCR for Irf7 relative to Rps29.",
    "ncbi_link": "Ifnar1: 15975
Ifnlr1: 242700
Irf7: 54123
Rps29: 20090"
  },
  {
    "caption": "HaCaT keratinocytes were pre-treated for 2 h with the proteasome inhibitors MG132 (10 μm (G) followed by a 20h treatment with FGF7 (10 ng/ml) or vehicle. RNA samples were analyzed by qRT-PCR for IRF7 and IRF1 relative to RPLP0.",
    "ncbi_link": "RPLP0: 
IRF1: 3659
IRF7: 3665"
  },
  {
    "caption": "HaCaT keratinocytes were pre-treated for 2 h with epoxomicin (100 nM) (H), followed by a 20h treatment with FGF7 (10 ng/ml) or vehicle. RNA samples were analyzed by qRT-PCR for IRF7 and IRF1 relative to RPLP0.",
    "ncbi_link": "RPLP0: 
IRF1: 3659
IRF7: 3665"
  },
  {
    "caption": "Serum-starved HaCaT keratinocytes were treated with FGF7 (10 ng/ml (A and/or IFN-α (500-1000 U/ml) for 12-16 h. RNA was analyzed by qRT-PCR for ISGs relative to RPLP0 (A",
    "ncbi_link": "RPLP0: "
  },
  {
    "caption": "Serum-starved HaCaT keratinocytes were treated with FGF7 different concentrations as indicated (B)) and/or IFN-α (500-1000 U/ml) for 12-16 h. RNA was analyzed by qRT-PCR for ISGs relative to RPLP0",
    "ncbi_link": "RPLP0: "
  },
  {
    "caption": "(D) Human primary keratinocytes were starved and treated for 12 h with FGF7 (10 ng/ml) and/or IFN-α (1000 U/ml). RNA samples were analyzed by qRT-PCR for ISGs relative to RPLP0.",
    "ncbi_link": "RPLP0: "
  },
  {
    "caption": "(A) Serum-starved HaCaT cells were treated for 24 h with poly(I:C) (5 μg/ml) in the presence or absence of FGF7 (10 ng/ml). RNA samples were analyzed by qRT-PCR for IFNL1, IFNB, RSAD2, IRF1, IRF7, CGAS, TLR3 or DDX58, relative to RPLP0.",
    "ncbi_link": "RPLP0: 
CGAS: 115004
DDX58: 23586
IFNB: 3456
IFNL1: 282618
IRF1: 3659
IRF7: 3665
RSAD2: 91543
TLR3: 7098"
  },
  {
    "caption": "Serum-starved HaCaT cells were infected with HSV-1 (MOI=0.5) in the presence or absence of FGF7 (10 ng/ml) or IFN-α (1000 U/ml). Viral load was determined 24 h post infection (hpi) by qPCR for the HSV-1 Glyc-B gene relative to the human β-actin gene (ACTB) (A)",
    "ncbi_link": "ACTB: 
β-actin: 
Glyc-B: 24271469"
  },
  {
    "caption": "Serum-starved HaCaT cells (D) were infected with HSV-1 (MOI=0.5) in the presence or absence of FGF7 at the indicated concentrations. Virus load was determined by qPCR for HSV-1 Glyc-B relative to ACTB 24 hpi.",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "human primary keratinocytes (HPK, from two donors) (E) were infected with HSV-1 (MOI=0.5) in the presence or absence of FGF7 at the indicated concentrations. Virus load was determined by qPCR for HSV-1 Glyc-B relative to ACTB 24 hpi.",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "(F) Serum-starved HaCaT cells were infected with HSV-1 (MOI=0.5) in the presence or absence of FGF7, FGF10 or FGF2 (10 ng/ml). DNA samples were analyzed by qPCR for Glyc-D DNA relative to ACTB and protein lysates were analyzed by Western blot for Glyc-D and vinculin 10 hpi.",
    "ncbi_link": "ACTB: 
Glyc-D: "
  },
  {
    "caption": "(H) Serum-starved HaCaT cells were infected with HSV-1 in the presence or absence of FGF7 (10 ng/ml) or IFN-α (1000 U/ml). Viral load was determined 24 hpi by qPCR for the HSV-1 Glyc-B gene relative to ACTB or by Western blot for the viral protein Glyc-D and GAPDH.",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "(I) Serum-starved HaCaT cells were infected with HSV-1 (MOI = 0.5). Four hours hpi, infected cells were washed and incubated in fresh serum-free medium containing FGF7 (10 ng/ml). Viral load was measured 8 h later by qPCR for Glyc-B relative to ACTB.",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "(J) Serum-starved HaCaT keratinocytes were treated for 6 h with FGF7 (10 ng/ml). RNA samples were analyzed by qRT-PCR for NECT1 (encoding nectin-1) relative to RPLP0.",
    "ncbi_link": "RPLP0: 
NECT1: 5818
nectin-1: 5818"
  },
  {
    "caption": "Serum-starved HaCaT cells were infected with HSV-1 (MOI=0.5) +/- FGF7 (10 ng/ml), added at the indicated time points 12 h after infection, RNA samples were analyzed by qRT-PCR for RSAD2, IRF7 and IFNL2 relative to RPLP0 (B),",
    "ncbi_link": "RPLP0: 
IFNL2: 282616
IRF7: 3665
RSAD2: 91543"
  },
  {
    "caption": "Serum-starved HaCaT cells were infected with HSV-1 (MOI=0.5) +/- FGF7 (10 ng/ml), added at the indicated time points 12 h after infection, , DNA samples were analyzed by qPCR for Glyc-B DNA relative to ACTB (C),",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "Serum-starved HaCaT cells were infected with HSV-1 (MOI=0.5) +/- FGF7 (10 ng/ml), added at the indicated time points D) shows mean Glyc-B DNA and RSAD2, IRF7 and IFNL2 mRNA levels (based on results shown in Fig. 6B and C) in virus-infected cells treated for different periods with FGF7.",
    "ncbi_link": "IFNL2: 282616
IRF7: 3665
RSAD2: 91543
Glyc-B: 24271469"
  },
  {
    "caption": "(I, J) HaCaT cells were infected with the ZIKV PF13/251013-18 (MOI = 20) in the presence or absence of FGF7 (20 ng/ml). RNA samples were analyzed by qRT-PCR for OAS1 and MxA relative to RPLP0 72 hpi.",
    "ncbi_link": "RPLP0: 
MxA: 4599
OAS1: 4938"
  },
  {
    "caption": "(A) Serum-starved HaCaT cells were infected with HSV-1 (MOI = 0.5) in the presence or absence of FGF7 (10 ng/ml) and the FGFR kinase inhibitors AZD4547 (1 μM) or BGJ398 (3.5 μM). DNA and protein lysates were analyzed by qPCR for Glyc-B relative to ACTB or by Western blot for Glyc-D and GAPDH, respectively, 16 hpi.",
    "ncbi_link": "ACTB: 
Glyc-B: 24271469"
  },
  {
    "caption": "HaCaT cells were cultured in DMEM/10% FCS (B) infected with HSV-1 (MOI=0.5) in the presence or absence of AZD45347 (1 μM) and/or BGJ398 (3.5 μM). Viral load was determined by qPCR for Glyc-D relative to ACTB (B)",
    "ncbi_link": "ACTB: 
Glyc-D: "
  },
  {
    "caption": "(D, E) Adult C57BL/6 wild-type (D) or K5-R1/R2 mice and respective controls (E) were infected subcutaneously with HSV-1 (MOI = 10). RNA from infected skin was analyzed by qRT-PCR for Fgf7 relative to Rps29 (D) and DNA was analyzed by qPCR for ICP0, normalized to the host gene Tbx15 48 hpi (E).",
    "ncbi_link": "Tbx15: 
Fgf7: 14178
ICP0: 2703389
Rps29: 20090"
  },
  {
    "caption": "(A) Western blot analysis showing the expression of the WRNIP1 protein in wild-type cells (shWRNIP1WT) and WRNIP1-deficient (shWRNIP1) or mutant (shWRNIP1T294A) cells. MRC5SV fibroblasts were used as a positive control. The membrane was probed with an anti-FLAG or anti-WRNIP1. GAPDH was used as a loading control. Below each lane of the blot the ratio of WRNIP1 protein to total protein, then normalised to MRC5SV, is reported.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(B) Experimental scheme of dual labelling of DNA fibers in shWRNIP1WT, shWRNIP1 and shWRNIP1T294A cells. Cells were pulse-labelled with CldU, and then subjected to a pulse-labelling with IdU.(C) Analysis of replication fork velocity (fork speed) in the cells under unperturbed conditions. The length of the green tracks were measured. Mean values are represented as horizontal black lines (ns, not significant; Student's t-test).",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(E) Experimental scheme of dual labelling of DNA fibers in shWRNIP1WT, shWRNIP1 and shWRNIP1T294A cells. Cells were pulse-labelled with CldU, treated with 4mM HU and then subjected to a pulse-labelling with IdU.(F) Graphs show the percentage of red (CldU) tracts (stalled forks) or red-green (CldU-IdU) contiguous tracts (restarting forks) in the cells. Mean shown, n = 3. Error bars represent standard error. (*, p < 0.05; **, p < 0.01; Student's t test). Representative DNA fiber images are shown. Scale bars, 10 µm.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(G) Experimental scheme of dual labelling of DNA fibers in shWRNIP1WT, shWRNIP1 and shWRNIP1T294A cells. Cells were sequentially pulse-labelled with CldU and IdU as indicated, then treated or not with 4 mM HU.(H) Representative IdU tract length distributions in all cell lines under unperturbed conditions (left graph) or after HU treatment (right graph). Median tract lengths are given in parentheses. See also Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are shown. Scale bars, 10 µm.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(A) Experimental scheme of dual labelling of DNA fibers in wild-type cells (shWRNIP1WT) or WRNIP1-deficient cells (shWRNIP1). Cells were sequentially pulse-labelled with CldU and IdU as indicated, then left untreated or treated with 4 mM HU in combination or not with 50 µM Mirin.(B) Representative IdU tract length distributions in shWRNIP1WT (left graph) or shWRNIP1 cells (right graph) after treatment. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are shown. Scale bars, 10 µm.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(A) Evaluation of ssDNA accumulation at parental-strand by immunofluorescence microscopy analysis in wild-type (shWRNIP1WT) or WRNIP1-deficient (shWRNIP1) cells. Experimental design of ssDNA assay is shown. Cells were labelled with IdU for 24 h, as indicated, washed and left to recover for 2 h, then treated or not with 4 mM HU. In parallel samples, the MRE11 activity is chemically inhibited with 50 µM Mirin, alone or in combination with HU-induced replication stress. After treatment, cells were fixed and stained with an anti-IdU antibody without denaturing the DNA to specifically detect parental ssDNA. Horizontal black lines represent the mean SE; n = 3. Error bars represent standard error (ns, not significant; **, p<0.01; ****, p<0.0001; two-tailed Student's t test). Representative images are shown. DNA was counterstained with DAPI (blue).",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(B) Analysis of chromatin binding of MRE11 and RAD51 in shWRNIP1WT and shWRNIP1 cells. Chromatin fractions of cells, treated or not with 4 mM HU, were analysed by immunoblotting. The membrane was probed with the anti-WRNIP1, anti-MRE11 and anti-RAD51 antibodies. LAMIN B1 was used as a loading for the chromatin fraction. Total amount of RAD51 and MRE11 (Input) in the cells was determined with the relevant antibodies. LAMIN B1 was used as a loading control. In the graph, the fold increase respect to the wild-type untreated of the normalized ratio of the chromatin-bound RAD51 (or MRE11)/ total RAD51 (or MRE11) is reported for each cell line.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(C) Analysis of DNA-protein interactions between ssDNA and endogenous RAD51 in shWRNIP1WT and shWRNIP1 cells by in situ PLA assay. Experimental designed used for the assay is given. Cells were labelled with IdU for 24 h, as indicated, washed and left to recover for 2 h, then treated or not with 4 mM HU for 4 h. Next, cells were fixed, stained with an anti-IdU antibody without denaturing the DNA to specifically detect parental-strand ssDNA, and subjected to PLA assay as described in the \"Experimental procedures\" section. Antibodies raised against IdU or RAD51 were used to reveal ssDNA or endogenous RAD51 respectively. Each red spot represents a single interaction between ssDNA and RAD51. No spot has been revealed in cells stained with each single antibody (negative control). DNA was counterstained with DAPI (blue). Representative images of the PLA assay are given. Graph shows the number of PLA spots per cell. Horizontal black lines represent the mean value (ns, not significant; **, p < 0.01; two-tailed Student's t test); n = 3.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(D) Localization of WRNIP1, MRE11 and RAD51 to stalled replication forks. Forks were isolated by CldU-co-immunoprecipitation (CldU-IP). shWRNIP1WT or shWRNIP1 cells were pulse-labelled with CldU, then fixed or treated with HU. Cells were cross-linked, and the nuclear extracts were isolated (Input) and subjected to CldU-IP using an anti-CldU antibody (CldU-IP). The membranes were probed with the anti-WRNIP1 or anti-RAD51 antibodies. After stripping, the membranes were probed with an anti-MRE11 antibody. LAMIN B1 and GAPDH were used as loading controls (Input). Ponceau S was used as a loading control of CldU-IP. Dot blot analysis was performed to confirm that equal amounts of immunoprecipitatedDNA from each sample. 10% of each IP was loaded on a nitrocellulose membrane. The membrane was probed with an anti-CldU antibody. The graph shows the normalized ratio of the proteins co-immunoprecipitated with CldU (CldUCo-IP proteins)/ the total of labelled DNAimmunoprecipitated with CldU (CldUIP) for each cell line after replication stress from two independent experiments. The dots in the graph represent the individual data points from each single experiment. Horizontal black line represents the mean value from two replicates; n = 2.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(A) Experimental scheme of pulse-labelling of DNA fibers in wild-type cells (shWRNIP1WT) or WRNIP1-deficient cells (shWRNIP1). Cells were labelled with IdU and exposed or not to 25 μM RAD51 inhibitor, then treated or not with 4 mM HU.(B) Representative IdU tract length distributions in shWRNIP1WT cells (left graph) or shWRNIP1 cells (right graph). Median tract lengths are reported in parentheses. See Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are reported. Scale bars, 10 µm.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(C) Scheme of DNA fiber tract analysis in shWRNIP1 cells. Cells were transfected with an empty vector or a plasmid expressing a wild-type human RAD51, and 48 h thereafter labelled with IdU and treated or not with 4 mM HU.(D) Representative IdU tract length distributions in shWRNIP1 cells or shWRNIP1 cells expressing exogenous wild-type RAD51 after HU exposure. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are given. Scale bars, 10 µm. Western blot shows the expression of the RAD51 protein in shWRNIP1 cells. The membrane was probed with an anti-RAD51. LAMIN B1 was used as a loading control.",
    "ncbi_link": "RAD51: 5892///5889///5890///5888
WRNIP1: 56897"
  },
  {
    "caption": "(A) Co-immunoprecipitation experiments in HEK293T cells transfected with empty vector or FLAG-WRNIP1 plasmid. Cells were treated or not with HU. After treatment, cell lysates were immunoprecipitated (FLAG-IP) using anti-FLAG antibody. The presence of WRNIP1, BRCA2 and RAD51 was assessed by immunoblotting using the anti-FLAG, anti-RAD51 and anti-BRCA2 antibodies, respectively. Whole cell extracts were analysed (Input). The membrane was probed with the same antibodies used for IP. GAPDH was used as a loading control.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(B) Analysis of protein-protein interactions between WRNIP1 and endogenous RAD51 in wild-type (shWRNIP1WT) or WRNIP1-mutant (shWRNIP1T294A) cells by in situ PLA assay. Cells were labelled with IdU for 24 h, washed and left to recover for 2 h, then treated or not with 4 mM HU. Antibodies raised against FLAG-Tag and RAD51 were used to reveal FLAG-WRNIP1 or endogenous RAD51 respectively. Each red spot represents a single interaction between WRNIP1 and RAD51. No spot has been revealed in cells stained with each single antibody (negative control). DNA was counterstained with DAPI (blue). Representative images of the PLA assay are shown. Graph shows the mean number of PLA spots per cell SE. Error bars represent standard error (ns, not significant; two-tailed Student's t test); n = 3.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(C) Experimental scheme of pulse-labelling of DNA fibers in wild-type cells (shWRNIP1WT) or WRNIP1-deficient cells (shWRNIP1). Cells were transfected with BRCA2 siRNA (siBRCA2), and 48 h thereafter labelled with IdU, then treated or not with 4 mM HU.(D) Representative IdU tract length distributions in shWRNIP1WT/siBRCA2 or shWRNIP1siBRCA2 cells treated or not with HU. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test. Representative DNA fiber images are reported. Scale bars, 10 µm. Western blot shows BRCA2 depletion in shWRNIP1WT and shWRNIP1 cells. The membrane was probed with an anti-BRCA2 or anti-WRNIP1. GAPDH was used as a loading control.",
    "ncbi_link": "BRCA2: 675
WRNIP1: 56897"
  },
  {
    "caption": "(E) Experimental scheme of pulse-labelling of DNA fibers in shWRNIP1 cells. Cells were transfected with control siRNA (shWRNIP1siCtrl) or FBH1 siRNA (shWRNIP1siFBH1), and 48 h thereafter labelled with IdU, then treated or not with 4 mM HU.(F) Representative IdU tract length distributions in shWRNIP1siCtrl or shWRNIP1siFBH1 cells with or without HU treatment. Representative DNA fiber images are reported. Scale bars, 10 µm. Western blot shows FBH1 depletion in the cells. The membrane was probed with an anti-FBH1. GAPDH was used as a loading control. Median tract lengths are given in parentheses. See Tables S1 and S2 for details on the data sets and statistical test.",
    "ncbi_link": "FBH1: 84893
WRNIP1: 56897"
  },
  {
    "caption": "(G) Analysis of chromatin binding of RAD51 in shWRNIP1 cells depleted for FBH1. Cells were transfected with control siRNA (shWRNIP1siCtrl) or FBH1 siRNA (shWRNIP1siFBH1), and 48 h treated or not with HU for 4h. Chromatin fractions of cells were analysed by immunoblotting. The membrane was probed with the anti-FBH1 and anti-RAD51 antibodies. LAMIN B1 was used as a loading for the chromatin fraction. Total amount of RAD51 (Input) in the cells was determined with the relevant antibodies. GAPDH was used as a loading control. The ratio of the RAD51/LAMIN B1 signal (chromatin) is reported below each lane.",
    "ncbi_link": "FBH1: 84893
WRNIP1: 56897"
  },
  {
    "caption": "(A) Analysis of DNA damage accumulation. Wild-type (shWRNIP1WT), WRNIP1-deficient (shWRNIP1) or mutant (shWRNIP1T294A) cells were treated or not with 4 mM HU for 4 h, then subjected to -H2AXimmunofluorescence microscopy. Graph shows data presented as mean of -H2AX-positive cells SE from three independent experiments; n = 3. Error bars represent standard error (*, p < 0.1; **, p < 0.01; two-tailed Student's t test). Representative images of nuclei showing the different number of foci per nucleus are reported.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(B) Analysis of DNA breakage accumulation. shWRNIP1WT, shWRNIP1 and shWRNIP1T294A cells were treated as in (A), then subjected to alkaline Comet assay. Graph shows data presented as mean tail moment SE from three independent experiments; n = 3. Error bars represent standard error (*, p < 0.1; **, p < 0.01; two-tailed Student's t test). Representative images are shown.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(C) Evaluation of cell death. shWRNIP1WT shWRNIP1 and shWRNIP1T294A cells were treated or not with 4 mM HU for 16 h. Cell viability was evaluated by LIVE/DEAD fluorescent assay. Data are expressed as mean of dead cells SE from three independent experiments; n = 3. Error bars represent standard error (*, p < 0.1; **, p < 0.01; two-tailed Student's t test). Representative images of double-staining of viable (green) and dead (red) cells are shown.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(D) Experimental scheme for evaluation of the chromosomal aberrations is shown. shWRNIP1WT shWRNIP1 and shWRNIP1T294A cells were treated or not with 4 mM HU, then left to recover for 16h in drug-free medium and metaphases collected with colcemid. Next, cells were fixed and processed as reported in \"Supplemental information\" section. Dot plot shows the number of chromosomal aberrations per cell. Horizontal black lines represent the mean SE. Error bars represent standard error (ns, not significant; **, p < 0.01; two-tailed Student's t test). Representative Giemsa-stained metaphases of cells treated or not with 4 mM HU. Arrows indicate chromosomal aberrations.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(E) Experimental scheme of the Mirin aberration analysis is given. The experiment was carried out as in (D) but cells were pre-treated or not with 50 µM Mirin. Dot plot shows the effect of Mirin exposure on the number of chromosome aberrations per cell in shWRNIP1 cells. Horizontal black lines represent the mean SE. Error bars represent standard error (ns, not significant; **, p < 0.01; two-tailed Student's t test). Representative Giemsa-stained metaphases of shWRNIP1 cells treated with Mirin alone or in combination with HU. Arrows indicate chromosomal aberrations.",
    "ncbi_link": "WRNIP1: 56897"
  },
  {
    "caption": "(F) Experimental design of the chromosomal aberration assay is reported. shWRNIP1 cells were transfected with control siRNAs (siCtrl) or FBH1 siRNA (siFBH1). Fourth-eight hours thereafter, cells were treated or not with 4 mM HU and then left to recover for 16 h. Metaphases were collected with colcemid and prepared as reported in \"Supplemental information\" section. Dot plot shows the number of chromosomal aberrations per cell. Western blot shows FBH1 depletion in the cells. The membrane was probed with an anti-FBH1. GAPDH was used as a loading control. Horizontal black lines represent the mean SE. Error bars represent standard error. (**, p < 0.01; two-tailed Student's t test).",
    "ncbi_link": "FBH1: 84893
WRNIP1: 56897"
  },
  {
    "caption": "(B) ACE2 gene expression summary in human tissues in 61 different tissues and cells in NX. Cut-off for what is regarded as expressed was set to 1.0 NX.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "Male, 12wk wildtype (WT; C57Bl/6J) or obese/diabetic monogenic (db/db; BKS.Cg-m+/+ Lepr DB/J; N = 4/group, A-E), New Zealand Black (NZB) and polygenic obese/prediabetic New Zealand Obese (NZO; n=4/group; F-J), as well as young (i.e. 3 mo) and aged (i.e.22 mo; n = 5/group; K-O), mice were fed ad libitum (fed) or fasted for 24h (fasted). Serum non-esterified fatty acids (A, F, K), triglycerides (B, G, L) and ketone bodies (C, H, M) were measured. In addition, serumacylcarinitine profiling was conducted and medium-chain (D, I, N) and long-chain (E, J, O) acylcarnitine concentrations are shown.",
    "ncbi_link": "db: 16847
Lepr: 16847"
  },
  {
    "caption": "In another cohort of mice, ex vivo long-chain fatty acid (LCFA) metabolism, including uptake (P), oxidation (Q) and non-oxidative LCFA disposal (NOFAD; R), in precision cut liver slices from fed and fasted WT and db/db mice (n = 3/ group; 4 slices per mouse), were determined. In addition, in slices from fasted mice, glucose output was determined in the presence of incubation with NEFA (BSA-NEFA) or vehicle (BSA) (S).",
    "ncbi_link": "db: 16847"
  },
  {
    "caption": "Liver mRNA expression of Growth Arrest and DNA Damage inducible 45 alpha (Gadd45a; A, D, G), beta (Gadd45b; B, E, H) and gamma (Gadd45g; C, F, I) was measured in fed and fasted obese/diabetic monogenic (db/db (n=4/group); A,-C), obese/pre-diabetic polygenic New Zealand Obese (NZO (n=4/group; D-F), and aged C57Bl/6J (22mo; n = 5/group; G-I) as well as corresponding lean, young wildtype (WT) mice (n=4/group). Matched controls for the NZO and aged mice were New Zealand Black (NZB) and 12wk old C57Bl/6J (12wk) mice, respectively.",
    "ncbi_link": "Gadd45a: 13197
Gadd45b: 17873
Gadd45g: 23882
db: 16847"
  },
  {
    "caption": "Male, GADD45β+/+ (WT; n=6) or GADD45β-/- mice (KO; n=4) were fed ad libitum (fed) or fasted for 24h (fasted), and subsequently refed for 24h. O2 consumption rate (A), CO2 production rate (B) and respiratory exchange ratio (C) were measured by indirect calorimetry.",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "In a distinct cohort, male GADD45β+/+ (WT; n=5) or GADD45β-/- mice (KO; n= 8) were fed ad libitum (fed) or fasted for 24h (fasted). Serumnon-esterified fatty acids (D) and ketone bodies (E) as well as serum (F) and liver (G) triglycerides (TG) were measured.",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "Serum TG (H), NEFA (I), and blood glucose (BG, J) concentrations during an oral lipid tolerance test in overnight fasted GADD45β+/+ (WT; n = 5) or GADD45β-/- (KO; n=5) mice.",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "Bloodglucose excursion during and intraperitoneal insulin tolerance test (K) as well as fasting bloodglucose (L), seruminsulin (M), and HOMA-IR (N) in GADD45β+/+ (WT; n = 6) or GADD45β-/- mice (KO, n = 9) chronically fed a normal- (NFD) or high (HFD) fat diet. Data are mean ± SEM.",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "Male, GADD45β+/+ (WT) or GADD45β-/- mice (KO) were fed ad libitum (fed) or fasted for 24h (fasted) and ex vivo liver slice long-chain fatty acid (LCFA) metabolism was measured including LCFA uptake (A), oxidation (B) and non-oxidative LCFA disposal (NOFAD) was calculated (C).",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "Gadd45b mRNA expression was measured from fractionated parenchymal hepatocytes (Hepas) as well as non-parenchymal cells (NP) from C57Bl/6J mice fed ad libitum (fed) or fasted for 24h (fasted); n=3/group (E).",
    "ncbi_link": "Gadd45b: 17873"
  },
  {
    "caption": "Male, C57Bl/6J mice with (AAV-G45b miR) or without (AAV-NC miR) liver-hepatocyte-restricted GADD45β silencing were fed or fasted for 24h (n = 6/group) and serum levels of non-esterified fatty acids (NEFA; F) as well as liver triglyceride (TG) concentration (G) were measured.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "Male, GADD45β+/+ (WT; n=16) or GADD45β-/- mice (KO; n=15) fasted for 24h (fasted) with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (n = 7-8/group). LiverTG concentration (H) was measured.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "Male, C57Bl/6J mice with (AAV-G45b miR; n= 15) or without (AAV-NC miR, n = 13) liver-hepatocyte-restricted GADD45β silencing were chronically fed a normal (NFD) or high (HFD) fat diet (n = 6-8/group). Fasting blood glucose (I) and serum insulin (J) were measured from which HOMA-IR was calculated (K).",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "Male, 12wk wildtype (WT; C57Bl/6J) or obese/diabetic (db/db; BKS.Cg-m+/+ Lepr DB/J) with (AD-G45b OE) or without (AD-NC) prior liver-restricted GADD45β over-expression were fasted and blood glucose ( A) and serum insulin (B) were measured from which HOMA-IR was calculated (C) (n = 4-6/group). Data are mean ± SEM. Effect of genotype/viral manipulation, * p < 0.05, ** p < 0.01, *** p < 0.001. Effect of nutritional state: # p < 0.05, ## p < 0.01, ### p < 0.001.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873
db: 16847
Lepr: 16847"
  },
  {
    "caption": "Liver GADD45B mRNA expression from men with (T2D) or without (NGT) type 2 diabetes (n = 14-23/group).",
    "ncbi_link": "GADD45B: 4616"
  },
  {
    "caption": "Scatter plots fasting plasma triglycerides (E) and glucose (F) in correlation with liver GADD45B mRNA expression (n = 37). Inserts show r2 values and p values from Spearman's correlation test. The statistical test used and respective p-value outputs can be found in Appendix Table S1.",
    "ncbi_link": "GADD45B: 4616"
  },
  {
    "caption": "Male, GADD45β+/+ (WT; n=16) or GADD45β-/- mice (KO; n=15) fasted for 24h (fasted) with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (n = 7-8/group). Liver mRNA expression of Gadd45b (A) as well as fatty acid metabolic genes (B) encompassing transport (Slc28a2, Slc27a5, Cd36), intracellular binding (Fabp1, Dbi) and metabolism (Acly, Dgat1, Atgl, Hsl).",
    "ncbi_link": "Acly: 104112
Cd36: 12491
Dbi: 13167
Dgat1: 13350
Fabp1: 14080
G45b: 17873
Gadd45b: 17873
GADD45β: 17873
Hsl: 16890
Atgl: 66853
Slc27a5: 26459
Slc28a2: 269346"
  },
  {
    "caption": "C: Representative immunoblots of FATP2, CD36, FABP1 and GADD45β from liver whole tissue lysate (W) as well as fractionated organelles/intraceuular structures including nuclei (N), mitochondria (MT), microsomes (MS) and cytoplasm (C), from GADD45β+/+ (WT) and GADD45β-/- (KO) mice. D: Quantified band densities of FABP1 enrichment from fractions in C (n = 4/group).",
    "ncbi_link": "GADD45β: 17873"
  },
  {
    "caption": "E: Liver fraction enrichment of FABP1 from male, GADD45β+/+ (WT) or GADD45β-/- (KO) fasted for 24h with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (n = 4/group). Insert shows a representative FABP1 immunoblot.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "F: Liver fraction enrichment of FABP1 from obese/diabetic male db/db mice fasted for 24h with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (n = 4/group). Insert shows a representative FABP1 immunoblot.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873
db: 16847"
  },
  {
    "caption": "G: FABP1 and GADD45B immunoblots from Flag-immunoprecipitations (IP-FLAG) or mock IP (IP-HA) from liver input samples from mice with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression. Shown is a representative immunoblot from 3 separate experiments using 3 different input samples per condition.",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "H: Liver long chain acyl-CoA (LC-acyl-CoA) concentrations were determined in GADD45β+/+ (WT) or GADD45β-/- (KO) mice (H; n=6/ group) with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (I; n =5/group).",
    "ncbi_link": "G45b: 17873
GADD45β: 17873"
  },
  {
    "caption": "Liver LC-acyl-CoA concentrations were determined in wildtype (WT; C57Bl/6J) or obese/diabetic (db/db; BKS.Cg-m+/+ Lepr DB/J) with (AD-G45b OE) or without (AD-NC) liver-restricted GADD45β over-expression (J; n=4/group).",
    "ncbi_link": "G45b: 17873
GADD45β: 17873
db: 16847
Lepr: 16847"
  },
  {
    "caption": "Growth analysis of wild type Xcc8004, EPS deficient mutants (B5 and B12), ndvB and ndvB (pHMJ) grown in PS medium (A); PS medium containing 50 µm extracellularion chelator, diethylenetriaminepentaacetic acid (DETAPAC) (B); or supplemented with either with (C) secreted glucan (0.5 mg/ml); (D) xanthan (0.5 mg/ml); (E) FeSO4 (40µM); and (F) MnCl2 (40µM). Data shown are mean ± SD (n=3). From here onward, until not mentioned, the 'n' indicates three biological replicates.",
    "ncbi_link": "ndvB: 
pHMJ: "
  },
  {
    "caption": "(B) Colorimetric iron-binding assay. Glucan from diverse source binds Fe2+ iron. Extracellular (ECG) or periplasmic (PPG) glucan isolated from the wild type Xcc8004 or the ndvB (pHM1J); commercial glucan from yeast, barley and Euglena purchased from Sigma Aldrich. Glucans from various sources were incubated with FeSO4 at room temperature for 15 min, amount of free iron was determined using the standard concentration of ferrozine-Fe2+ complex.",
    "ncbi_link": "ndvB: 998673"
  },
  {
    "caption": "Xanthomonas campestris: (A) wild type Xcc 8004; (B) B5 (EPS deficient) (C) B12EPS deficient); (D) ndvB (glucan deficient); and (E) ndvB(pHM1J)+ (complementing strain); cells were treated in the presence or absence of either FeSO4, H2O2 or FeSO4+Dp (dipyridyl) were analyzed for ROS by monitoring DCF fluorescence with flow cytometry.",
    "ncbi_link": "B12: 1002177
ndvB: 998673
B5: 999354"
  },
  {
    "caption": "(A) Wild type E. coli (MG1655); ΔopgG (ΔmdoG; JW1035) and ΔopgH (ΔmdoH; JW1037), mutants blocked in periplasmic glucan synthesis were grown in LOS medium, and cells were treated in the presence or absence of either FeSO4, H2O2 or FeSO4+DP (dipyridyl) were analyzed for ROS by monitoring DCF fluorescence with flow cytometry.",
    "ncbi_link": "mdoG: 
mdoH: 
opgG: 945005
opgH: 945624"
  },
  {
    "caption": "(G) Sera  from wild-type (WT) BKS and Leprdb/db mice, aged 4, 8, and 18 weeks, B6 mice, fed with a normal diet (ND) and a high fat diet  (HFD) for 4 weeks, and humans, healthy volunteers and diabetic patients (T2D), were quantified for Pdia4  level using an anti-Pdia4 ELISA kit. Data information: Data from 3 experiments more are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "Lepr: 16847"
  },
  {
    "caption": "(A) Survival rate and  life span of WT, Pdia4-/-(KO), and Pdia4tg/tg (TG) mice on Leprdb/db background from birth to 120 weeks Data information: The number of mice (n) is indicated in parentheses. Data from over 3 experiments are presented as the mean ± SD. Log rank test were used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "Lepr: 16847
Pdia4: 12304"
  },
  {
    "caption": "(B) Pancreata  of 18-week-old WT and Pdia4-/- (KO) mice  on BKS or Leprdb/db background were stained  with anti-insulin   (αIns) antibody and dihydroethidium (DHE) (left). Islet  area (μm2) and relative fluorescence intensity (RFI) were quantified (right). Scale bar: 100 μm. The dash circles indicate   islet  regions. Data information: Data from over 3 experiments are presented as the mean ± SD. one-way ANOVA test were used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "Lepr: 16847
Pdia4: 12304"
  },
  {
    "caption": "(A) The islets of WT, Pdia4-/- (KO) and Pdia4tg/tg (TG) BKS mice were isolated and grown in complete DMEM medium containing 3.3 mM (LG) and 30 mM glucose (HG) for 12 h. The  islets stained  with propidium iodide  (PI), photographed, and quantified. Scale bar = 50 μm. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "Pdia4: 12304"
  },
  {
    "caption": "(A) Ultrastructure of mitochondria and insulin granules in typical β-cells of 3 mouse lines on BKS and  Leprdb/db backgrounds. Arrows indicate the mitochondria  whereas arrowheads indicate insulin granules. Scale bar = 1 μm. Data information: A total of 15-23 images per group were analyzed. Data from each group are presented as the mean ± SD.",
    "ncbi_link": "Lepr: 16847"
  },
  {
    "caption": "(E) The construct encoding Flag-Pdia4 or its mutants and that expressing Myc/Flag-tagged Ndufs3  (left) or    p22phox  (right) were co-transfected into 293T cells. Total lysates (TL) and anti-Myc immunoprecipitates  (Myc IP) underwent  immunoblotting analysis. N-terminal Flag tag, catalytic domains (a, a' and a''), non-catalytic domains (b and b'), and C-terminal KEEL are indicated. Pdia4* is a mutant of Pdia4    whose 3 CGHC motifs were changed into 3 SGHS motifs (a*, a'* and a''*).",
    "ncbi_link": "Flag: 
Myc: 
p22phox: 1535
Ndufs3: 4722
Pdia4: 9601"
  },
  {
    "caption": "(F) The construct encoding Myc/Flag-tagged  p22phox, Ndufs3 or their mutants and that expressing Flag-tagged Pdia4  were co-transfected into  293T cells. Total lysates (TL) and anti-Myc immunoprecipitates  (Myc IP) underwent  immunoblotting analysis using anti-Flag antibody.",
    "ncbi_link": "Flag: 
Myc: 
p22phox: 1535
Ndufs3: 4722
Pdia4: 9601"
  },
  {
    "caption": "(A)  Min6 cells infected with a lentivirus expressing a scramble RNAi (GK), a Pdia4 RNAi (KD) and a  Pdia4 cDNA (OVE) were sorted and tested for the Pdia4 protein level  (left). The cells were incubated with NAC (1 mM) and then  stained  with MitoSOX  or CellROX in response to 0.5 mM (LG) and 25 mM (HG) glucose for an additional 30 min. Signal from MitoSOX (middle) and CellROX  (right) was re-plotted into histograms. Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "Pdia4: 12304"
  },
  {
    "caption": "(B) Min6 cells infected with a lentivirus expressing a scramble RNAi (GK) and an RNAi of Ndufs3  (Ndufs3 KD) or p22phox (p22phox KD) were selected and tested for levels of Ndufs3 (1st column), mitochondrial ROS (2nd column, MitoSOX),  p22phox  (3rd column), and cytosolic ROS (4th column, CellROX). The cells were grown in the presence of 0.5 mM (LG) and 25 mM (HG)  glucose. (C) The same experiments as (B) were conducted except that Min6 cells were infected with a lentivirus expressing a cDNA of truncated Ndufs3 (tNdufs3) and p22phox (tp22phox). ( Data information: Data from 3 experiments are presented as the mean ± SD. One-way ANOVA test was used for statistical analysis of differences between groups, and P (*) < 0.05; P (**) < 0.01 and P (***) < 0.001 are considered statistically significant.",
    "ncbi_link": "p22phox: 1535
Ndufs3: 68349"
  },
  {
    "caption": "(D) 293T cells, which were transfected with the construct encoding Flag-Pdia4  and that expressing  Myc/Flag-tagged p22phox or Ndufs3, were treated with GHTT  (28 μM) for 30 min. The cells were lysed and incubated with anti-Pdia4 antibodies plus protein G beads. Their total lysates (TL) and immunoprecipitates (IP) underwent immunoblotting  analysis with anti-Flag antibody.",
    "ncbi_link": "Flag: 
Myc: 
p22phox: 1535
Ndufs3: 4722
Pdia4: 9601"
  },
  {
    "caption": "A Immunoblot analysis of RAB35 depletion in hTERT-RPE1 cells transfected with two independent siRNAs targeting RAB35 (RAB35-1, RAB35-2) or a non-targeting siRNA control (Neg). 24 h after transfection, cells were serum-starved for further 48 h. β-tubulin served as a loading control.",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "C, D hTERT-RPE1 cells and hTERT-RPE1 cells stably expressing siRNA-resistant GFP-RAB35 were treated and stained for GFP, acetylated tubulin (acetyl. tub.) and DNA. Representative images in (C) of cells treated with Neg or RAB35 siRNA. Regions within white boxes shown at higher magnifications to the right. Scale bars, 10 µm. Cilia length quantifications in (D) are shown as box-and-whisker plots. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment of three is shown (n ≥ 50 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P < 0.05, ** P < 0.01, *** P < 0.001, n.s.: non-significant; P-values: hTERT-RPE1-Neg vs. hTERT-RPE1-RAB35-1 P < 0.0001, hTERT-RPE1-Neg vs. hTERT-RPE1-RAB35-1 P < 0.0001, hTERT-RPE1-RAB35-1 vs. GFP-RAB35-RAB35-1 P = 0.0249, hTERT-RPE1-RAB35-2 vs. GFP-RAB35-RAB35-2 P = 0.0056)",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "E Immunoblot analysis of Rab35 depletion in IMCD3 cells transfected with pool of siRNAs targeting mouse Rab35 or a non-targeting siRNA control (Neg). 24 h after transfection, cells were serum-starved for further 48 h. GAPDH served as a loading control.",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "I Immunoblot analysis of NIH3T3 wild type (WT) and Rab35 knockout (KO) cell lines. β-tubulin served as a loading control.",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "NIH3T3 WT and Rab35 KO cell lines were serum-starved for 24h and stained for acetylated tubulin (acetyl. tub.) and DNA. Quantification of ciliation in (J). Data are mean ± S.E.M. of 3 independent experiments (n ≥ 100 cilia per experimental condition).",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "NIH3T3 WT and Rab35 KO cell lines were serum-starved for 24h and stained for acetylated tubulin (acetyl. tub.) and DNA. Representative images in (K). Regions within white boxes shown at higher magnifications at the bottom. Scale bars, 10 µm. Cilia length quantifications in (L) are shown as box-and-whisker plots. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment of three is shown (n ≥ 100 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (**** P < 0.0001).",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "A Representative images of hTERT-RPE1 cells transiently expressing wild type (WT), GDP-bound (S22N) or GTP-bound (Q67L) GFP-tagged RAB35. Cells were serum-starved for 24 h and stained for polyglutamylated tubulin (polyglu. tub.) and DNA. Higher magnification images of the cilia region shown in smaller panels. Scale bars; 10 µm.",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "Quantification of GFP-RAB35 ciliary localisation (B) in hTERT-RPE1 cells transiently expressing indicated GFP-RAB35 constructs or GFP. Data are mean ± S.E.M. of 3 independent experiments. Statistical significance according to ANOVA followed by Bonferroni post-hoc test ( ** P < 0.01; P-values: (B) P = 0.0015",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "Quantification of ciliation (C) in hTERT-RPE1 cells transiently expressing indicated GFP-RAB35 constructs or GFP. Data are mean ± S.E.M. of 3 independent experiments. Statistical significance according to ANOVA followed by Bonferroni post-hoc test ( ** P < 0.01; P-values: (C) P = 0.0062).",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "Quantification of ciliary length in hTERT-RPE1 cells transiently expressing indicated GFP-RAB35 constructs or GFP. Cilia length quantification in (D) is shown as box-and-whisker plots. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n ≥ 50 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P < 0.05, ** P < 0.01; P-values: GFP vs. GFP-RAB35-S22N P = 0.0015, GFP vs. GFP-RAB35-Q67L P = 0.0158)",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "Analysis of cilia length in hTERT-RPE1 cells depleted of GEF DENND1B) and GAP (TBC1D10A regulators of RAB35. Cells transfected with indicated siRNAs were serum-starved for 48 h and stained for acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (E). Regions within white boxes shown at higher magnifications to the right. Scale bars; 10 µm.",
    "ncbi_link": "DENND1B: 163486
RAB35: 11021
TBC1D10A: 83874"
  },
  {
    "caption": "Analysis of cilia length in hTERT-RPE1 cells depleted of GEF (DENND1A, DENND1B) and GAP (TBC1D10A, TBC1D10B) regulators of RAB35. Cells transfected with indicated siRNAs were serum-starved for 48 h and stained for acetylated tubulin (acetyl. tub.) and DNA. Cilia length quantification in (F) is shown as box-and-whisker plots. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n ≥ 50 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (** P < 0.01, *** P < 0.001; P-values: Neg vs. DENND1B P = 0.0033, Neg vs. TBC1D10A P = 0.0008)",
    "ncbi_link": "DENND1A: 57706
DENND1B: 163486
RAB35: 11021
TBC1D10A: 83874
TBC1D10B: 26000"
  },
  {
    "caption": "G Quantification of ciliary localisation of GFP-RAB35 in hTERT-RPE1 cells stably expressing GFP-RAB35 treated Data are mean ± S.E.M. of 5 independent experiments. Statistical significance according to ANOVA followed by Bonferroni post-hoc test (* P < 0.05, *** P < 0.001; P-values: Neg vs. DENND1B P < 0.0001, Neg vs. TBC1D10A P = 0.0322).",
    "ncbi_link": "GFP: 
DENND1B: 163486
RAB35: 11021
TBC1D10A: 83874"
  },
  {
    "caption": "A Immunostaining of representative images of KV embryos at 8 somite stage in which mRNA encoding for mCherry or mCherry-Rab35 WT was injected. Staining of acetylated tubulin was used as cilia marker. Inset shows a higher magnification image of the cilia region, displaying colocalization of mCherry-Rab35 and acetylated tubulin. Scale bar, 10 µm.",
    "ncbi_link": "mCherry: 
Rab35: 11021"
  },
  {
    "caption": "D Organ situs was determined by observing the heart position at 30 hours post-fertilisation (hpf), and the liver position at 53 hpf, by in situ hybridisation with a probe for foxa3, in controls (Mismatch MO and non-injected [WT]) and Rab35 MO. Situs solitus means left heart and liver; situs inversus means right heart and liver; and heterotaxia means any other possible combination of the heart and liver position.",
    "ncbi_link": "foxa3: 30559"
  },
  {
    "caption": "E Whole-mount in situ hybridization with the dand5 probe at 8 somite stage (13 hpf) in wild type non-injected embryos and mismatch morphants, both presenting right-sided distribution of dand5, and Rab35 morphants presenting bilateral localization of the dand5 probe. Scale bar, 50 µm. Graph shows quantification of embryos (%) with bilateral or right-sided dand5 localisation from both conditions. Statistical significance according to Fisher Exact test (** P = 0.0002)",
    "ncbi_link": "dand5: 791454"
  },
  {
    "caption": "F-I Immunostaining of representative images of KV embryos at 8 somite stage in which: (F) Mismatch or Rab35 MO was injected, as well as a co-injection of Rab35 MO with mRNA encoding mCherry-Rab35 WT [Rescue]; (H) mRNA encoding mCherry or mCherry-tagged Rab35 WT, Rab35-Q67L or Rab35-S22N were injected. Acetylated tubulin is shown in green as cilia marker. Quantification of KV cilia length in (F) and (H) is shown respectively in (G) and (I) as box-and-whisker plots of 3 independent experiments. N ≥ 8 embryos and n > 300 cilia per experimental condition. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (** P < 0.01, *** P < 0.001, ns. not significant; Mismatch vs Rab35 MO, P < 0.001; Cherry vs Rab35-SN, P = 0.0063; ). Scale bars, 10 µm.",
    "ncbi_link": "Cherry: 
mCherry: 
Rab35: 11021"
  },
  {
    "caption": "A, B hTERT-RPE1 cells and hTERT-RPE1 cells stably expressing siRNA-resistant GFP-RAB35 transfected with non-targeting siRNA control (Neg) or Rab35 siRNA, were serum-starved for 48 h and stained for ARL13B, GFP, polyglutamylated tubulin (polyglu. tub.) and DNA. Representative images are shown in (A). Regions within white boxes shown at higher magnifications to the right. Scale bars; 10 µm. (B) Box-and-whisker plots show quantification of ciliary ARL13B intensity in arbitrary units (a. u.). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 25 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (** P < 0.01, *** P < 0.001, n.s.: non-significant; P-values: hTERT-RPE1-Neg vs. hTERT-RPE1-RAB35-1 P < 0.0001, hTERT-RPE1-Neg vs. hTERT-RPE1-RAB35-1 P = 0.0001, hTERT-RPE1-RAB35-1 vs. GFP-RAB35-RAB35-1 P = 0.0014, hTERT-RPE1-RAB35-2 vs. GFP-RAB35-RAB35-2 P = 0.0081).",
    "ncbi_link": "GFP: 
RAB35: 11021
Rab35: 11021"
  },
  {
    "caption": "C Immunoblot analysis of total ARL13B protein levels in control and RAB35-depleted cells. β-tubulin served as a loading control. The graph shows ARL13B protein levels normalized (norm.) to β-tubulin. Data are mean ± S.E.M. of 4 independent experiments.",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "D,E NIH3T3 wild type (WT) and Rab35 knockout (KO) cell lines were serum-starved for 24h and stained for Arl13b, acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (D). Higher magnifications of regions within white boxes shown at the bottom. Scale bars; 10 µm. (E) Box-and-whisker plots show quantification of ciliary Arl13b intensity in arbitrary units (a. u.). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 25 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P < 0.05; P-values: NIH3T3 WT vs. Rab35 KO#1 P = 0.0118, NIH3T3 WT vs. Rab35 KO#2 P = 0.0111).",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "F Immunoblot analysis of total ARL13B protein levels in serum-starved NIH3T3 WT and Rab35 KO cell lines. β-tubulin served as a loading control.",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "Quantification of ciliary ARL13B intensity in hTERT-RPE1 cells depleted of GEF (G) regulators of RAB35. Cells transfected with indicated siRNAs were serum-starved for 48 h and stained for ARL13B, acetylated tubulin and DNA. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 30 cilia per experimental condition). Statistical significance according ANOVA followed by Bonferroni post-hoc test (*** P < 0.001; P-values: (G) P = 0.0005",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "Quantification of ciliary ARL13B intensity in hTERT-RPE1 cells depleted of GAP (H) regulators of RAB35. Cells transfected with indicated siRNAs were serum-starved for 48 h and stained for ARL13B, acetylated tubulin and DNA. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 30 cilia per experimental condition). Statistical significance according ANOVA followed by Bonferroni post-hoc test (*** P < 0.001; P-values: (H) P < 0.0001).",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "I, J Ciliary ARL13B intensity quantification of hTERT-RPE1 cells transiently overexpressing GFP or GFP-RAB35. Cells were serum-starved for 24 h and stained for ARL13B, acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (I). Higher magnification images of the cilia region are shown at the bottom. Scale bars; 5 µm. Cells with (RAB35+ cilia) and without (RAB35- cilia) GFP-RAB35 ciliary localisation are compared in (J). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 25 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (*** P =0.0004).",
    "ncbi_link": "GFP: 
RAB35: 11021"
  },
  {
    "caption": "A HEK293T cells were transiently co-transfected with ARL13B-FLAG and GFP or GFP-RAB35. Cells were cultured either in full growth medium (+serum) or serum-starved for the final 8 h before harvesting. Immunoprecipitations (IP) were performed using anti-GFP beads. Cell lysates (2.5% of input) and immunoprecipitates were loaded on the same gel, subjected to immunoblot (I) analysis with indicated antibodies and detected with the same exposure.",
    "ncbi_link": "FLAG: 
GFP: 
ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "C HEK293T cells were transiently co-transfected with mCherry-RAB35 together with GFP or indicated ARL13B-GFP wild type, mutant or truncation constructs. Cells were serum-starved for the final 8 h before harvesting. IPs were performed using anti-GFP beads and interacting proteins detected by immunoblotting (IB).",
    "ncbi_link": "GFP: 
mCherry: 
ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "D HEK293T cells were transiently transfected with ARL13B-FLAG and serum-starved for the final 8 h before harvesting. HEK293T cell lysates expressing ARL13B-FLAG were subjected to pull-down with GFP-RAB35 bound to anti-GFP beads and preloaded with either no nucleotide, GTPγS or GDP. Bound proteins and cell lysates (1% of input) were analysed by immunoblotting. The graph shows the ratio of precipitated ARL13B and RAB35, normalized to the no nucleotide control. Data are mean ± S.E.M. of 3 independent experiments. Statistical significance according ANOVA followed by Tukey post-hoc test (* P =0.0333).",
    "ncbi_link": "FLAG: 
ARL13B: 200894"
  },
  {
    "caption": "E HEK293T cells were transiently transfected with mCherry-RAB35 and serum-starved for the final 8 h before harvesting. HEK293T cell lysates expressing ARL13B-FLAG were subjected to pull-down with ARL13B-GFP bound to anti-GFP beads and preloaded with either no nucleotide, GTPγS or GDP. Bound proteins and cell lysates (1% of input) were analysed by immunoblotting. The graph shows the ratio of precipitated ARL13B and RAB35, normalized to the no nucleotide control. Data are mean ± S.E.M. of 3 independent experiments. Statistical significance according ANOVA followed by Tukey post-hoc test (* P =0.0466)",
    "ncbi_link": "FLAG: 
mCherry: 
ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "A, B hTERT-RPE1 cells transfected with non-targeting siRNA control (Neg) or RAB35 siRNA, were serum-starved for 48 h and stained for INPP5E, ARL13B, acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (A). Regions within white boxes shown at higher magnifications to the right. Scale bars, 10 µm. (B) Box-and-whisker plots show quantification of ciliary INPP5E intensity in arbitrary units (a. u.). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 50 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (*** P < 0.001; P-values: Neg vs. RAB35-1 P < 0.0001, Neg vs. RAB35-2 P = 0.0002).",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "C For co-depletion experiments, hTERT-RPE1 cells were first transfected with Neg or RAB35 siRNA. After 24h, a second transfection with Neg or ARL13B siRNA was performed and cells were serum starved for 48 h and stained as in (A). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 40 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (** P = 0.0017).",
    "ncbi_link": "ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "D, E NIH3T3 wild type (WT) and Rab35 knockout (KO) cell lines were serum-starved for 24h and stained for Innpp5e, acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (D). Higher magnifications of regions within white boxes shown at the bottom. Scale bars; 10 µm. (E) Box-and-whisker plots show quantification of ciliary Inpp5e intensity in arbitrary units (a. u.). Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n > 25 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P < 0.05, *** P < 0.001; NIH3T3 WT vs. Rab35 KO#1 P < 0.0001, NIH3T3 WT vs. Rab35 KO#2 P = 0.0345).",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "F, G Localisation of the PI(4,5)P2 sensor PH-PLCδ1-GFP to cilia in live NIH3T3 WT and Rab35 KO cells. Cilia are marked with HTR6-RFP. Representative images are shown in (F). Higher magnification images of the cilia region shown to the right. Scale bars; 10 µm. Quantification of localisation in (G). Data are mean ± S.E.M. of 3 independent experiments (n > 100 cilia per experimental condition). Statistical significance according to two-way ANOVA (* P = 0.0242).",
    "ncbi_link": "Rab35: 77407"
  },
  {
    "caption": "hTERT-RPE1 cells transfected with indicated siRNAs were serum-starved for 48 h and treated with SMO agonist (SAG) or vehicle control (DMSO) for the last 24 h. Cells were stained for SMO, acetylated tubulin and DNA. Representative images are shown in (A). Regions within white boxes shown at higher magnifications to the right. Scale bars, 10 µm. Graph in (B) shows the percentages of SMO-positive (SMO+) cilia. Data are mean ± S.E.M. of 5 independent experiments. Statistical significance according to ANOVA followed by Bonferroni post-hoc test (*** P < 0.001; P-values: Neg+SAG vs. RAB35-1+SAG P < 0.0001, Neg+SAG vs. RAB35-2+SAG P = 0.0033)",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "hTERT-RPE1 cells transfected with indicated siRNAs were serum-starved for 48 h and treated with SMO agonist (SAG) or vehicle control (DMSO) for the last 24 h. (C) Box-and-whisker plots show quantification of the average SMO intensity in the ciliary area marked by acetylated tubulin staining. All cilia: cilia identified with acetylated tubulin staining. SMO+ cilia: cilia with discernible SMO localisation. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n ≥ 30 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P < 0.05, *** P < 0.001; P-values: Neg+SAG vs. RAB35-1+SAG (all cilia) P < 0.0001, Neg+SAG vs. RAB35-2+SAG (all cilia) P = 0.0024, Neg+SAG vs. RAB35-1+SAG (SMO+ cilia) P < 0.0007, Neg+SAG vs. RAB35-2+SAG (SMO+ cilia) P = 0.0205)",
    "ncbi_link": "RAB35: 11021"
  },
  {
    "caption": "For co-depletion experiments, hTERT-RPE1 cells were first transfected with Neg or RAB35 siRNA. After 24h, a second transfection with Neg or ARL13B siRNA was performed and cells were treated as in (A). Representative images are shown in (D). Regions within white boxes shown at higher magnifications as insets. Scale bars, 10 µm. Graph in (E) shows the percentages of SMO-positive cilia. Data are mean ± S.E.M. of 5 independent experiments. Statistical significance according to ANOVA followed by Bonferroni post-hoc test (* P = 0.0151, n.s.; non-significant).",
    "ncbi_link": "ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "For co-depletion experiments, hTERT-RPE1 cells were first transfected with Neg or RAB35 siRNA. After 24h, a second transfection with Neg or ARL13B siRNA was performed and cells were treated (F) show quantification of ciliary SMO intensity. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n ≥ 30 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (* P = 0.0142, n.s.; non-significant).",
    "ncbi_link": "ARL13B: 200894
RAB35: 11021"
  },
  {
    "caption": "Ciliary SMO intensity quantification in hTERT-RPE1 cells transiently expressing GFP, wild type ARL13B-GFP (WT) or the ciliary-targeting defective mutant ARL13B-V358A. Cells were serum-starved and treated with SAG for 24 h and stained for SMO, acetylated tubulin (acetyl. tub.) and DNA. Representative images are shown in (G).",
    "ncbi_link": "GFP: 
ARL13B: 200894"
  },
  {
    "caption": "Ciliary SMO intensity quantification in hTERT-RPE1 cells transiently expressing GFP, wild type ARL13B-GFP (WT) or the ciliary-targeting defective mutant ARL13B-V358A. Cells were serum-starved and treated with SAG for 24 h and stained for SMO Box-and-whisker plots in (H) show quantification of ciliary SMO intensity. Horizontal lines show 25, 50 and 75th percentiles; whiskers extend to minimum and maximum values. One representative experiment out of three is shown (n ≥ 25 cilia per experimental condition). Statistical significance according to Kruskal-Wallis followed by Dunn's post-hoc test (** P = 0.0046).",
    "ncbi_link": "GFP: 
ARL13B: 200894"
  },
  {
    "caption": "C. Fluorescence micrographs of HeLa cells transfected with plasmids encoding human GFP-Cwh43, GFP-Cwh43-k696fs or GFP-Cwh43-Leu533ter fusion proteins. To label the ER, HeLa cells were transduced with a baculovirus encoding a fluorescently labeled RFP-calreticulin fusion protein containing an ER retention signal (RFP-calreticulin-KDEL). To label the Golgi apparatus, cells were immunostained for golgin-97 (red). When compared with wild type GFP-Cwh43, GFP-Cwh43-k696fs and GFP-Cwh43-Leu533 showed decreased association with the Golgi apparatus (but not the ER) and were diffusely distributed throughout the cytoplasm. Scale bar is approximately 5 µm.",
    "ncbi_link": "GFP: 
Cwh43: 80157"
  },
  {
    "caption": "D. Western blot analysis of total membrane, aqueous and lipid (GPI-anchor-containing) Triton X-114 extracts derived from wild type HeLa cells and two independent CRISPR CWH43 knockout (KO) HeLa cell lines in which a mutated CWH43 gene encodes a protein that is truncated near Leu533 and CWH43 mRNA and protein are markedly reduced. Cells were transfected to overexpress a control GFP plasmid, a plasmid encoding human wild type Cwh43 with GFP fused to the N-terminus, or a plasmid encoding human CWH43 harboring the iNPH-associated mutation (Lys696AsnfsTer23) with GFP fused to the N-terminus. The Western blot was stained using an antibody directed against CD59, a GPI-anchored protein.",
    "ncbi_link": "CRISPR: 
GFP: 
CWH43: 80157
Cwh43: 80157"
  },
  {
    "caption": "A. Scatter plot comparing ventricular volume from CWH43WT/WT (wild type, WT), heterozygous CWH43WT/M533, homozygous CWH43M533/M533 and CWH43M533/A530 mice at 6 months. Ventricular volume was calculated from T2-weighted MR images of the mouse brain using a custom automated computer algorithm. Horizontal bars indicate the mean of the measurements in each column. Statistical significance for each mutant mouse line compared to WT was determined using the unpaired t-test (P=0.0015 for CWH43WT/M533; P=0.0014 for CWH43M533/M533; P=0.006 for CWH43M533/A530).",
    "ncbi_link": "CWH43: 80157
CWH43: 231293"
  },
  {
    "caption": "D. Box plot showing rotarod performance data for CWH43WT/WT, CWH43WT/M533, CWH43M533/M533 and CWH43M533/A530 mice at 7 months of age. Data shown are the mean, 1st quartile, 3rd quartile, minimum and maximum for each group of mice. Statistical significance was determined using the unpaired t-test. When compared to wild type CWH43WT/WT mice (n=10), balance time on the rotarod was decreased significantly among heterozygous CWH43WT/M533 mice (*P=0.04, n=8), homozygous CWH43M533/M533 mice (*P=0.03, n=7), and compound heterozygous CWH43M533/A530 mice (*P=0.03, n=4).",
    "ncbi_link": "CWH43: 231293"
  },
  {
    "caption": "Scanning electron micrographs of the ependymal surface of the lateral ventricle of CWH43 WT and CWH43M533/M533 mice. Scale bar is approximately 40 µm. The graph on the right quantifies the data from the electron micrographs on the left. Data shown are the mean ± SEM. * = P=0.004, n = 4, unpaired t-test.",
    "ncbi_link": "CWH43: 231293"
  },
  {
    "caption": "Western blot analysis of total membrane, aqueous and lipid (GPI-anchor-containing) Triton X-114 extracts derived from wild type, CWH43M533/M533 and CWH43WT/M533mouse brain or kidney. The Western blot was stained using an antibody directed against CD59, a GPI-anchored protein.",
    "ncbi_link": "CWH43: 231293"
  },
  {
    "caption": "Fluorescence immunohistochemistry for CD59 in the ependymal layer and choroid plexus of the lateral ventricle from CWH43WT/WT, CWH43M533/M533 and CWH43M533/A530 mice. Arrowheads point to apical surfaces of ependymal and choroid plexus cells. Nuclei are counterstained using DAPI (blue). Scale bar is approximately 5 µm.",
    "ncbi_link": "CWH43: 231293"
  },
  {
    "caption": "Cloning and characterization of APG9. A, Wild-type (WT; SEY6210), apg9 (THY154), apg9Δ (JKY007), and the apg9Δ strain transformed with single copy (CEN; pAPG9(414)) or multicopy (2μ; pAPG9(424)) plasmids encoding APG9 were grown to log phase in SMD. Protein extracts were prepared and analyzed by immunoblot using antiserum to API as described in Materials and Methods. The positions of precursor and mature API are indicated. The APG9 gene complements the prAPI accumulation phenotype of the apg9Δ mutant.",
    "ncbi_link": "APG9: 851406
apg9: 851406"
  },
  {
    "caption": "B, WT (SEY6210), apg9Δ (JKY007), and the apg9Δ strain transformed with pAPG9(414) centromeric plasmid were grown in SMD and transferred to SD(−N) as described in Materials and Methods. Aliquots were removed at the indicated times and spread onto YPD plates in triplicate. Numbers of viable colonies were determined after two to three days. The APG9 gene complements the starvation-sensitive phenotype of the apg9Δ mutant.",
    "ncbi_link": "apg9: 851406
APG9: 851406"
  },
  {
    "caption": "Apg9p is an unglycosylated, integral membrane protein. A, Wild-type (WT; SEY6210), apg9Δ (JKY007), and the apg9Δ strain transformed with single copy (CEN) or multicopy (2μ) plasmids encoding APG9 were grown to log phase in SMD. Protein extracts were prepared and analyzed by immunoblot using antiserum to Apg9p. Apg9p is detected as an ∼125-kD protein.",
    "ncbi_link": "Apg9: 851406
apg9: 851406
APG9: 851406"
  },
  {
    "caption": "D, Strain CTD1 harboring a multicopy 3×HA APG9 plasmid was grown in YPD and converted to spheroplasts as described in Materials and Methods. A crude lysate was prepared and treated with or without endo H as indicated overnight at 37°C and analyzed by immunoblots with anti-HA antibodies or anti-CPY serum. Endo H treatment removes the N-linked glycosyl residues of CPY, causing a shift in its electrophoretic mobility. In contrast, Apg9p is not glycosylated and remains unchanged in the presence or absence of endo H treatment.",
    "ncbi_link": "APG9: 851406"
  },
  {
    "caption": "Apg9p does not comigrate with typical endomembrane markers in sucrose density gradients. A and B, Strain STY1 (pep4Δ) was grown in YPD to log-phase, and osmotically lysed. Lysates were precleared, loaded on a sucrose density gradient ranging from 18-55% (wt/wt), and centrifuged for 2.5 h at 174,000 g as described in Materials and Methods. Fractions were collected from the top (fraction number 1) to the bottom (fraction number 16). Fractions were subjected to SDS-PAGE and immunoblot with antiserum against Apg9p and: in A, Kex2p (trans Golgi network), Pho8p (vacuole), and Pma1p (plasma membrane); and in B, Sec12p (ER) and Pep12p (endosome). The graphs in panels A and B are from the same gradient, but are presented separately for clarity.",
    "ncbi_link": "pep4: 855949"
  },
  {
    "caption": "Apg9p localizes to large perivacuolar punctate structures. Immunofluorescence microscopy of strains CTD1 (apg9Δ), KSL12C (vps4Δ), and SKD6-1D (apg6Δ) transformed with the multicopy plasmid 3×HA APG9. Cells were grown in YPD to log phase (vegetative), and incubated further in SD(−N) medium with 1 mM PMSF for 3 h (starvation). The cells were fixed with formaldehyde and examined by immunofluorescence microscopy as described in Materials and Methods. Anti-HA and FITC-conjugated antibodies mark Apg9p (left), and the vacuole can be visualized by Nomarski optics (middle). An overlay is shown in the right panels.",
    "ncbi_link": "apg9: 851406
apg6: 855983
vps4: 856303"
  },
  {
    "caption": "Apg9p does not comigrate with prAPI in a strain that accumulates Cvt/autophagic vesicles. Strain TK415 (ypt7Δ) was grown in YPD to log-phase, and osmotically lysed. Lysates were precleared, centrifuged at 100,000 g for 1 h, and the pellet fraction resuspended and centrifuged a second time. The resulting pellet fraction was subsequently loaded on a sucrose density gradient ranging from 18-55% (wt/wt), and centrifuged for 16 h at 174,000 g as described in Materials and Methods. 16 fractions were collected starting from the top and subjected to SDS-PAGE and immunoblot with antisera against Apg9p and API. The graph represents an average of two experiments.",
    "ncbi_link": "ypt7: 855012"
  },
  {
    "caption": "In vivo examination of the Apg9pGFP fusion protein. Wild-type (SEY6210) cells expressing Apg9pGFP from a multicopy plasmid were grown in SMD to midlog phase and labeled with FM 4-64 to stain the vacuoles as described in Materials and Methods. The labeled cells were viewed directly with a Leica DM IRB confocal microscope. Large, punctate Apg9pGFP structures appear juxtaposed to the FM 4-64-labeled vacuole membranes. In addition, smaller punctate structures appear throughout the cytoplasm.",
    "ncbi_link": "Apg9: 851406"
  },
  {
    "caption": "Ultrastructural localization of Apg9p for immunoelectron microscopy. Strain STY1 (pep4Δ) expressing 3×HA Apg9p was grown in YPD to log phase and transferred to SD(−N) medium for 2 h. The cells were fixed and stained with anti-HA antibody and 5-nm colloidal gold-conjugated goat anti-mouse IgG as described in Materials and Methods. A, Section showing autophagic bodies in the vacuole lumen. B, Section showing a cytosolic autophagosome. Apg9p is seen in patches near the vacuole, but not on autophagic bodies or autophagosomes. AB, autophagic body; AP, autophagosome; N, nucleus; V, vacuole; VM, vacuolar membrane. Arrows point to areas of concentrated Apg9p.",
    "ncbi_link": "Apg9p: 851406
pep4: 855949"
  },
  {
    "caption": "Vesicle accumulation test and kinetic analysis of prAPI import in the temperature conditional Apg9p mutant. A, Morphological analysis of apg9Δ indicates an import defect at an early step in the pathway. Wild-type (YW5-1B) and apg9Δ (CTD1) cells were grown in YPD (vegetative) or transferred to SD(−N) (starvation) for 3 h in the presence of PMSF (starvation) and examined by DIC (Nomarski) microscopy (Zeiss Axioplan). PMSF inhibits the degradation of autophagic bodies. Under starvation conditions, wild-type cells accumulate autophagic bodies when vesicle breakdown is blocked. However, under the same conditions, apg9Δ cells do not accumulate autophagic bodies, indicating that Apg9p is required for a step before vesicle fusion and release of the autophagic body into the vacuolar lumen. The apg9Δ strain transformed with the APG9 plasmid shows the same result as wild-type (data not shown). B, The apg9ts strain is tightly blocked for prAPI import at nonpermissive temperature. Wild-type (SEY6210) and apg9Δ (JKY007) cells transformed with the apg9ts centromeric plasmid were incubated at 24 and 38°C for 5 min, pulse-labeled for 10 min, and then subjected to nonradioactive chase reactions for the indicated times. Samples at each time point were immunoprecipitated with antiserum to API and resolved by SDS-PAGE as described in Materials and Methods. API-immunoprecipitated bands were quantified by a Molecular Dynamics STORM PhosphorImager and the results are presented in the graph. The percent mature API was determined by dividing the mature API value over the sum of the precursor and mature API values for each time point.",
    "ncbi_link": "apg9: 851406
APG9: 851406
Apg9p: 851406"
  },
  {
    "caption": "Analysis of the apg9ts strain indicates Apg9p is directly required for the vesicle formation step. A, The nature of prAPI binding and pelleting in the apg9ts strain. Spheroplasts of apg9ts were labeled for 10 min and chased for 30 min at 38°C. The spheroplasts were osmotically lysed in a buffer containing no salt (20 mM Pipes, pH 6.8) or a physiological concentration of salt (100 mM KOAc, 50 mM KCl, 5 mM MgCl2, 20 mM Pipes, pH 6.8) and pelleted at 5,000 g. All samples were immunoprecipitated with antiserum to API and the cytosolic marker PGK. apg9ts retains the salt dependent binding and pelleting of prAPI. B, prAPI in the apg9ts strain accumulates in both a membrane-associated state and a large pelletable complex. Spheroplasts of apg9ts and ypt7Δ were labeled for 10 min and chased for 30 min at 38°C. The labeled spheroplasts were then osmotically lysed and separated into supernatant (S) and pellet (P) fractions by centrifugation at 5,000 g for 5 min. An aliquot was removed for the total lysate control (T). The pellet fraction (P) was resuspended in 15% Ficoll-400 in gradient buffer (20 mM Pipes, 5 mM MgCl2, complete EDTA-free protease inhibitor cocktail) in the presence or absence of Triton X-100 and overlaid with 13 and 2% Ficoll-400 in gradient buffer. The step gradients were centrifuged at 13,000 g for 10 min. Membrane-containing float (F), nonfloat (NF), and pellet (P2) fractions were immunoprecipitated with antiserum to API as described in Materials and Methods. The position of prAPI is indicated. C, prAPI in the apg9ts strain is protease accessible. Spheroplasts isolated from apg9ts and ypt7Δ cells were pulse-labeled for 10 min and chased for 30 min at 38°C. The labeled spheroplasts were then osmotically lysed and separated into low-speed supernatant (S) and pellet (P) fractions after a 5,000 g centrifugation step. The pellet fractions were subjected to protease treatment in the absence or presence of 0.2% Triton X-100 as described in Materials and Methods. The resulting samples were immunoprecipitated with antiserum to API and PGK. The immunoprecipitated bands were quantified by a Molecular Dynamics STORM PhosphorImager. The percent protease-protected prAPI was determined by dividing the value for prAPI in the protease-treated sample by the value for total prAPI before protease treatment. The percent PGK was determined by dividing the supernatant (S) or pellet (P) value over the sum of the S and P values.",
    "ncbi_link": "apg9: 851406
Apg9p: 851406
ypt7: 855012"
  },
  {
    "caption": "(A) Mitochondrial morphology in HeLa cells depleted of Sept2, Sept7 and Sept9. Mitochondria were labeled with mitotracker (green). Scale bar: 10 µm. The inset represents a twofold enlargement. (B) Quantification of mean mitochondrial length in mock treated cells and in cells depleted of Sept2, Sept7 and Sept9. n>250 individual mitochondria from three independent experiments.",
    "ncbi_link": "Sept2: 4735
Sept7: 989
Sept9: 10801"
  },
  {
    "caption": "(C) Mitochondrial morphology in mock treated cells or HeLa cells depleted of Sept2 and then transfected with empty vector, siRNA-resistant HA-tagged Sept2 (Sept2-rescue) or Sept7 (Sept7-rescue). Mitochondria were labeled with mitotracker (shown in green), asterisks mark transfected cells. Scale bar: 10 µm, insets are twofold enlargements. (D) Quantification of mean mitochondrial length in mock treated cells, in cells depleted of Sept2 or in cells depleted of Sept2 and transfected with siRNA-resistant Sept2 (Sept2-rescue) or Sept7 (Sept7-rescue). n>200 individual mitochondria from two independent experiments.",
    "ncbi_link": "Sept2: 4735
Sept7: 989"
  },
  {
    "caption": "(E) Mock treated or Sept2 depleted U2OS cells stained for Sept2 (green) and the Golgi apparatus (GM130, red), the ER (Sec61b-GFP, displayed in red) or peroxisomes (PMP70, red). (F) Quantification of the mean Golgi area (n=40 cells, three independent experiments) (G) Quantification showing the percentage of ER traversing well-resolved mitochondrial tubules (n=15 cells from three independent experiments). (H) Quantification of average peroxisome counts per cell (n=40 cells from three independent experiments). Scale bar: 10 µm, insets are enlarged twofold.",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(A) Live cell imaging of mock treated or Sept2 depleted U2OS cells analyzed with the mito-PA-GFP mitochondrial fusion assay. Mito-PA-GFP is photoactivated in the indicated ROI and the decrease in fluorescence is followed in the same ROI, correcting for cell movement (B) Quantification of mitochondrial fusion rates in mock treated or Sept2 depleted cells expressed as a means of three independent experiments SEM. (C) Quantification of fission rates in mock and Sept2 depleted cells. n=116 fission events for Sept2 siRNA, n=83 fission events for mock, two independent experiments.",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(D) Live cell imaging of U2OS cells stably transfected with a GFP targeted to the mitochondrial outer membrane (OM-GFP), showing delayed FCCP-induced mitochondrial fission in Sept2 depleted cells compared to mock treated cells. White arrowheads point at fission examples, yellow arrowheads to looping. Scale bar: 10 µm, insets are enlarged twofold. (E) Quantification of mitochondrial elongation (long /short axis) in mock treated and FCCP treated U2OS cells showing increased elongation in Sept2 depleted cells compared to mock treated cells, mean of four independent experiments SEM.",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(C) GST pulldown of recombinant Sept2 with GST-Drp1 or GST alone showing that Sept2 is able to interact directly with Drp1.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "(A) Immunofluorescence microscopy of Sept2 (blue), mitochondria (Tom20, red) and Drp1 (green) in mock treated and Sept2 depleted cells. Scale bar: 10 µm, insets are enlarged fourfold. (B) Quantification of mitochondria-associated Drp1 in mock treated and Sept2 depleted cells (mean of 3 independent experiments, n=44-51 cells) (C) Average distance between mitochondria-associated Drp1 oligomers (representative experiment with n>25 individual mitochondria).",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(D) HeLa cytosol and crude mitochondrial fractions prepared from mock and Sept2 siRNA treated cells. The samples were analysed by western blotting with indicated antibodies, and show a decrease in mitochondria-associated Drp1 in Sept2 depleted cells.",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(A) Immunofluorescence microscopy analysis of P-MLC (green) recruitment to mitochondria (red, Tom20) in mock treated and Sept2 depleted HeLa cells. Insets show twofold enlargements. Scale bar: 10 µm. (B) Colocalization of P-MLC with mitochondria was assessed with Icy software and showed no difference between mock and Sept2 depleted cells.",
    "ncbi_link": "Sept2: 4735"
  },
  {
    "caption": "(C) Mock treated or Sept2 depleted Drp1 -/- MEF cells were labeled with mitotracker orange (red), treated for the indicated amount of time with 2µM FCCP and stained for actin with phalloidin (green). Insets are enlarged twofold.",
    "ncbi_link": "Drp1: 74006
Sept2: 18000"
  },
  {
    "caption": "(D) Immunofluorescence microscopy analysis of the actin binding proteins Arp3 and cofilin (green), colocalized with cytocrome c (red) and cortactin (green), colocalized with Hsp60 (red) in mock treated or Sept2 depleted Drp1 -/- MEF cells. Scale bars: 10 µm.",
    "ncbi_link": "Drp1: 74006
Sept2: 18000"
  },
  {
    "caption": "(E) Cytosol and crude mitochondria fractions were prepared from mock treated or Sept2 depleted Drp1 -/- MEF cells and analyzed by western blotting with the indicated antibodies.",
    "ncbi_link": "Drp1: 74006
Sept2: 18000"
  },
  {
    "caption": "(A) Live imaging of C. elegans expressing TOM70::GFP in body wall muscle cells. Depletion of the UNC-59 or UNC-61 led to an increase in mitochondrial network connectivity as shown by quantification in (B). Insets represent a twofold magnification. Scale bar: 10 µm.",
    "ncbi_link": "UNC-59: 173233
UNC-61: 179976"
  },
  {
    "caption": "(C) Live imaging of C. elegans body wall muscle cells expressing TOM70::GFP. Depletion of DRP-1 or UNC-61 caused an increase in mitochondrial elongation and network connectivity, which did not increase upon combination of DRP-1 and UNC-61. Insets represent a twofold magnification. Scale bar: 10 µm.",
    "ncbi_link": "DRP-1: 177336
UNC-61: 179976"
  },
  {
    "caption": "(B) Gpx4 protein was measured in liver of WT and PPARα-/- mice fed blank solvent or GW7647; n = 4 biological replicates.",
    "ncbi_link": "PPARα: 19013"
  },
  {
    "caption": "(E) Chromatin immunoprecipitation assays were performed on soluble formaldehyde-crosslinked chromatin isolated from untreated and GW7647-treated WT or PPARα-/- livers with polyclonal anti-PPARα antibodies (anti-PPARα) or control IgG. The final DNA extraction was polymerase chain reaction-amplified with a primer pair that covered the sequence in intron 3 of Gpx4.",
    "ncbi_link": "Gpx4: 625249
PPARα: 19013"
  },
  {
    "caption": "(D) TRF protein was measured in liver of WT and PPARα-/- mice fed blank solvent or GW7647. n = 4 biological replicates.",
    "ncbi_link": "PPARα: 19013"
  },
  {
    "caption": "G Verify the mobility of GFP (control) mRNA and GFP-MdCAX3 mRNA by RT-PCR in Mx leaf, stem, and root. The recombinant vectors (F) were transformed into A. tumefaciens GV3101 and introduced into Mx leaves by vacuum infiltration.",
    "ncbi_link": "CAX3: 
GFP: "
  },
  {
    "caption": "H GFP fluorescence image of the Mx roots under different treatment. Nuclei were labeled using DAPI. Scale Bar: 100 μm.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "H Ratio (488/440) image of BCECF fluorescence in the roots of MdCAX3-suppressed in leaves Md/Mx. Scale bars: 100 μm.",
    "ncbi_link": "CAX3: "
  },
  {
    "caption": "I Rhizosphere acidification of MdCAX3-suppressed in leaves Md/Mx. Bromocresol purple was used as a pH indicator for visualization. Scale bars: 1 cm.",
    "ncbi_link": "CAX3: "
  },
  {
    "caption": "F GUS staining in N. benthamiana leaves after transient co-expression of pro35S::GFP with proMxCXIP1:GUS or proMbCXIP1:GUS, and co-expression with pBI101:GUS as a control.",
    "ncbi_link": "CXIP1: 
GFP: 
GUS: "
  },
  {
    "caption": "G Interaction between MdCXIP1 and MdCAX3 tested by yeast two-hybrid (Y2H) assays. A dilution series of NMY51 yeast cells co-expressing MdCXIP1 and MdCAX3 cultured on SD/II and SDIV screening media. pPBT3-N (empty vector) co-expressed with MdCXIP1 was used as a negative control. X-gal was used in SD/-Trp/-Leu/-His/-Ade screening medium to further test for possible interactions.",
    "ncbi_link": "CAX3: 
CXIP1: "
  },
  {
    "caption": "C Fluorescence ratio (488/440 nm excitations) of BCECF fluorescence in the roots of MdCAX3 and MdCXIP1 co-overexpressing Mb. The central band represents the median and the box ranges showing the interquartile range and covers the central 50% of the data. The whiskers showing the minimum and maximum of the data. Three biological replicates; 3 roots were quantified for each replicate. Asterisks indicate statistically significant differences (***, P < 0.001; ANOVA, Tukey correction).",
    "ncbi_link": "CAX3: 
CXIP1: "
  },
  {
    "caption": "D Ratio (488/440) image of BCECF fluorescence in MdCAX3 and MdCXIP1 co-overexpressing Mb. Scale Bar: 100 μm. E Rhizosphere acidification in MdCAX3 and MdCXIP1 co-overexpressing Mb. Bromocresol purple was used as a pH indicator for visualization. Scale Bar: 1 cm.",
    "ncbi_link": "CAX3: 
CXIP1: "
  },
  {
    "caption": "D Cellular localization of Zn2+ (blue) in Mx and MdCAX3-suppressed Mx roots under Fe deficient conditions. Arrowhead indicates the cytoplasm. Scale Bars: 20 μm. E Fluorescence intensity detection at the position indicated by the long and narrow arrow in the Fig 6D.",
    "ncbi_link": "CAX3: "
  },
  {
    "caption": "C, D. Western blots against NPC1 and actin-β (ACTB) in total brain (C) and synaptosomes (D) from wt and NPC1nmf164 mice. Graphs show mean ± SEM NPC1 level normalized to ACTB as a percentage of control (wt) values (n=4 mice, 3 month-old, unpaired Student t test, **psynaptosomes= 0.0037).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "E. Western blots against NPC1 and actin-β (ACTB) in total brain extracts from wt and Npc1-null mice (NPC1KO) containing the same amount of protein (n=2 mice, 6 week-old).",
    "ncbi_link": "Npc1: 18145
NPC1: 18145"
  },
  {
    "caption": "F. Graph shows mean ± SEM mRNA levels of NPC1 in total extracts and in synaptosomes from wt and NPC1nmf164 mice (n=4 mice, 3 month-old).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "G. Western blots against NPC1 and actin-β (ACTB) in synaptosomes from wt and NPC1nmf164 mice in which cLTP was induced or not in the presence or absence of the protein synthesis inhibitor cycloheximide (CHX). Graphs show mean ± SEM NPC1 level normalized to ACTB as a percentage of control (wt non cLTP induced) values (n=3 mice, 3 month-old, 2-way ANOVA, ***p < 0.001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "H. To the left Western blots against NPC1 and actin-β (ACTB) in synaptosomal extracts from wt and NPC1nmf164 mice used as input for the immunoprecipitation assays shown in the right. Immunoprecipitates were pulled down with an anti-ubiquitin antibody and without it for negative control and analysed by western blot against NPC1. MG132 was used as proteasome inhibitor. Graphs show mean ± SEM levels of NPC1 normalized to ACTB in the inputs (left) (n=3, one-way ANOVA, *pWT+MG-132=0.0496, pNPC1nmf1+MG-132=0.0358) and of NPC1 associated to ubiquitin (right) (n=3 mice, 3 month-old, one-way ANOVA, *pNPC1nmf164= 0.0237, pNPC1nmf164+MG-132= 0.0386.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "A. Representative electron micrographs of synapses in the hippocampal CA1 region in wt and NPC1nmf164 mice (black arrows indicate post-synaptic densities, d-dendrite, sv-synaptic vesicles, m-mitochondria, MLB-multilamellar bodies).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "C. Mean ± SEM synaptic vesicle density (3,088 vesicles from 101 wt and 121 NPC1nmf164 synapses from 3 different mice (3 month-old) per group, unpaired Student t test, ***p < 0.0001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "D. Synaptic vesicle diameter (528 wt and 507 NPC1nmf164 vesicles from 3 different mice (3 month-old) per group).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "E. Mean ± SEM post-synaptic density length (101 wt and 121 NPC1nmf164 post-synaptic densities from 3 different mice (3 month-old) per group, unpaired Student t test, ***p < 0.0001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "G. Mean ± SEM cholesterol levels in synaptosomes (n=4 mice, 3 month-old, unpaired Student t test, *p = 0.0476) from wt and NPC1nmf164 mice expressed as percentage of wt mice.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following properties of Schaffer collateral-CA1 synaptic responses were recorded from wt and NPC1nmf164 mice. A. Basal synaptic transmission expressed as mean ± SEM EPSP slope (n= 9 slices from 5 WT mice and n=8 slices from 5 NPC1nmf164 mice, all mice 10 week-old, unpaired Student t test, * p150μA = 0.0368, p200μA = 0.0138); B. Mean ± SEM fibre volley amplitude (n=10 slices from 5 WT mice and n= 7 slices from 5 NPC1nmf164 mice, all mice 10 week-old); C. Mean ± SEM paired pulse facilitation (n=11 slices from 5 WT mice and n=10 slices from 5 NPC1nmf164 mice, all mice 10 week-old, unpaired Student t test, **p = 0.0011); D. LTP expressed as mean ± SEM percentage of EPSP slope over baseline (n=7 slices form 5 WT mice for WT and n=10 slices from 5 NPC1nmf164 mice, all mice 10 week-old, unpaired Student t test, ***p < 0.0001 in the last 10 min recording) ",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following properties of Schaffer collateral-CA1 synaptic responses were recorded from wt and NPC1nmf164 mice. E. LTD expressed as mean ± SEM percentage of EPSP slope over baseline (n=7 slices from 5 WT mice and n=12 slices from 5 NPC1nmf164 mice, all mice 10 week-old).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The behavioural tests were recorded from wt and NPC1nmf164 mice. F. Mean ± SEM exploration time of objects in novel and familiar location in the Object Placement Recognition test (n=10 mice, 10 week-old, 2-way ANOVA, *p = 0.0167).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The behavioural tests were recorded from wt and NPC1nmf164 mice. G. Mean ± SEM percentage of entry to the novel arm of the Y maze test (n=10 mice, 10 week-old; unpaired Student t test, **p = 0.0015). H. Mean ± SEM percentage of freezing time in the Contextual Fear Conditioning test (n=10 mice, 10 week-old; unpaired Student t test, ***p = 0.0002). I. Mean ± SEM distance covered during a 5 min period in the Open Field test (n=10 mice, 10 week-old). ",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "A. Mean ± SEM cholesterol level in plasma membrane fractions of hippocampal slice cultures from wt and NPC1nmf164 mice with or without cLTP induction (n=6, unpaired Student t test, *pwt = 0.0402",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "B. Western blot of NPC1 and ACTB in extracts of cultured hippocampal neurons from wt mice transfected or not with sh-scr or sh-NPC1 RNAs. Black bars indicate that the sh-NPC1 lane was not consecutive to the others but belongs to the same Western blot. Graph shows the 2 biological replicates mean ± SEM of NPC1 level normalized to ACTB as a percentage of the wt, non-transfected controls.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "C. Representative images of the cholesterol binding probe mCherry-D4 before and after cLTP in cultured hippocampal neurons from wt mice transfected with sh-scr or sh-NPC1 RNAs. Z-stack images acquired using a Nikon A1R+ confocal microscope were used to generate 3D images of the neurons.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "Western blots against NPC1 actin-β (ACTB) in total extracts (T) and biotin-streptavidin immunoprecipitates (S) from synaptosomes from wt and NPC1nmf164 mice in which cLTP was induced or not. Graphs show mean ± SEM of the levels of biotinylated-surface NPC1 as a percentage of the total amount of each protein (n=3 mice, 3 month-old, 2-way ANOVA, *pNPC1 = 0.0251",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "Western blots against CYP46A1 and actin-β (ACTB) in total extracts (T) and biotin-streptavidin immunoprecipitates (S) from synaptosomes from wt and NPC1nmf164 mice in which cLTP was induced or not. Graphs show mean ± SEM of the levels of biotinylated-surface CYP46A1 as a percentage of the total amount of each protein (n=3 mice, 3 month-old, 2-way ANOVA , *pCYP46A1 = 0.0371).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "F. Representative images of GluA1 immunocytochemical staining before and after cLTP in non-permeabilized (surface) and permeabilized (total) cultured hippocampal neurons expressing sh-scr or sh-NPC1 RNAs. Graph shows mean ± SEM GluA1 surface staining with respect to total in cLTP conditions, as a percentage of the sh-scr baseline (n=20 images per condition from 2 different experiments, 2-way ANOVA, ***psh-scr < 0.001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "A. Western blots against CYP46A1 and ACTB in extracts of total brain and synaptosomes from wt and NPC1nmf164 mice as a percentage of wt values. Graphs show 3 biological replicates mean ± SEM of CYP46A1 level normalized to ACTB in arbitrary units.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "B. Quantitative PCR of Cyp46 of total brain and synaptosomes from wt and NPC1nmf164 mice. 3 biological replicates mean ± SEM is shown.",
    "ncbi_link": "Cyp46: 13116
NPC1: 18145"
  },
  {
    "caption": "C. Mean ± SEM cholesterol levels in EFV-treated or non-treated synaptosomes from wt (n=5 mice, 14-week-old, unpaired Student t test, *p = 0.0233) and NPC1nmf164 (n=4 mice, 14 week-old, unpaired Student t test, *p = 0.0188) mice. EFV values are expressed as percentage of their corresponding non-treated controls in wt and NPC1nmf164 conditions.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "D. Basal synaptic transmission in EFV-treated and non-treated hippocampal slices from wt and NPC1nmf164 mice expressed as mean ± SEM EPSP slope (n=9 slices from 5 WT mice, n=11 slices EFV-treated from 5 WT mice, n=8 slices from 5 NPC1nmf164 mice and n=13 slices EFV-treated from 5 NPC1nmf164 mice, all mice 14-week-old, 2-way ANOVA, *p = 0.0117).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "E. LTP in EFV-treated and non-treated hippocampal slices from wt and NPC1nmf164 mice expressed as mean ± SEM percentage of EPSP slope over baseline (n=7 slices from 5 WT mice, n=9 slices EFV-treated from 5 WT mice, n=10 slices from 5 NPC1nmf164 mice and n=11 slices EFV-tretaed from 5 NPC1nmf164 mice, all mice 14-week-old, 2-way ANOVA, ***p < 0.0001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "F. Mean ± SEM paired pulse facilitation in EFV-treated and non-treated hippocampal slices from wt and NPC1nmf164 mice (n=11 slices from 5 WT mice, n=9 slices EFV-treated from 5 WT mice, n=10 slices from 5 NPC1nmf164 mice and n=11 slices EFV-tretaed from 5 NPC1nmf164 mice, all mice 14-week-old, 2-way ANOVA, **pNPC1nmf164=0.0027, *pNPC1nmf164+EFV=0.0229).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "Representative images of GluA1 immunocytochemical staining before and after cLTP induction in non-permeabilized (surface) and permeabilized (total) cultured hippocampal neurons expressing sh-scr or sh-NPC1 RNAs and treated or not with EFV. Graph shows the mean ± SEM GluA1 surface staining with respect to total after cLTP, as a percentage of the sh-scr baseline (n=20 images per condition from 2 separate experiments, 2-way ANOVA, ***psh-scr < 0.001, **psh-scr+EFV < 0.01, ***psh-NPC1+EFV < 0.001).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following analyses were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV A. Mean ± SEM 24(S)-hydroxycholesterol plasma level after 6 and 8 weeks of oral EFV treatment in wt (n=6 mice, 14 week-old and 16 week-old, 2-way ANOVA, **p6 weeks = 0.0023) and NPC1nmf164 (n=5 mice, 14 week-old and 16 week-old, 2-way ANOVA, ***p6 weeks < 0.0001; ***p8 weeks < 0.0001) mice.",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following analyses were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV B. Mean ± SEM body weight in grams in wt and NPC1nmf164 mice treated or not with EFV (n=4 mice, unpaired Student t-test, ***pNPC1nmf164 < 0.0001, **pNPC1nmf164+EFV = 0.0048)",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following behavioural tests were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV C. Mean ± SEM discrimination index as a normalized ratio of time spent with novel and familiar objects in the Object Placement Recognition test (n=6 mice, 10 week-old, 2-way ANOVA, **pWT/NPC1nmf164 = 0.0065, ***pNPC1nmf164/NPC1nmf164+EFV = 0.0008).",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following behavioural tests were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV D. Mean ± SEM percentage of entries in the novel arm of the Y maze test (n=10 mice, 10 week-old, 2-way ANOVA, ***p < 0.0001). E. Mean ± SEM percentage of freezing time in the Contextual Fear Conditioning test (n=10 mice, 10 week-old, 2-way ANOVA, **pNPC1 < 0.0025, *pNPC1+EFV < 0.0181). F. Mean ± SEM percentage of freezing time in the Cued Fear Conditioning test (n=10 mice, 10 week-old, 2-way ANOVA, *pNPC1 < 0.0453, **pNPC1+EFV < 0.0054). ",
    "ncbi_link": "NPC1: 18145"
  },
  {
    "caption": "The following analyses were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV G. Mean ± SEM cholesterol level in synaptosomes of wt and NPC1nmf164 mice treated or not with EFV expressed as percentage of the wt non-treated samples (n=4 mice, 14 week-old, 2-way ANOVA, *pNPC1 < 0.0476, *pNPC1+EFV < 0.0118).",
    "ncbi_link": "NPC1: 
NPC1: 18145"
  },
  {
    "caption": "The following analyses were assessed in wt and NPC1nmf164 mice treated or not with 0.09mg/kg/day EFV H. Representative fluorescence images of the CA1 hippocampal region from wt and NPC1nmf164 mice treated or not with EFV and stained with filipin and an antibody against LAMP1. White arrows indicate lysosome enlargement in the hippocampus of non-treated NPC1nmf164 mice. Graph to the right shows mean ± SEM fluorescence intensity associated to filipin per area in arbitrary units (n=4 mice, 14-week old, unpaired Student t-test, **pNPC1nmf164 = 0.0011, *pNPC1nmf164+EFV = 0.0273)). I. Survival graph for wt and NPC1nmf164 mice treated or not with EFV (n=5 mice, 2-way ANOVA, ***p < 0.0001). ",
    "ncbi_link": "NPC1: 
NPC1: 18145"
  },
  {
    "caption": "(a) Cells were transfected with control siRNA or with siRNA specific to IRGM (top) and DRP1 (bottom) for 48 h and protein samples from these cells were then analysed by immunoblotting with anti-IRGM and anti-DRP1 antibodies. Actin was used as a loading control.",
    "ncbi_link": "DRP1: 10059
IRGM: 345611"
  },
  {
    "caption": "(b) HeLa cells were treated with siRNA specific to either IRGM or DRP1 as indicated and were then labelled with MTR and analysed by live-cell confocal microscopy. Scale bars, 5 μm.",
    "ncbi_link": "DRP1: 10059
IRGM: 345611"
  },
  {
    "caption": "(c) Cells were treated with either control siRNA or with DRP1, IRGM, ATG7 or BECN1 (Beclin 1) siRNAs, labelled with MTR and the percentage of cells with mitochondrial morphologies ranging from normal, punctiform (dots) and elongated were quantified. Definition of mitochondrial morphologies and quantification criteria are given in Supplementary Information, Figure S2.",
    "ncbi_link": "ATG7: 10533
BECN1: 8678
DRP1: 10059
IRGM: 345611"
  },
  {
    "caption": "(d) Cells were transfected with either control siRNA or with siRNA specific to MFN1/MFN2, IRGM or IRGM and MFN1/MFN2, and then labelled with MTR and analysed for mitochondrial morphologies. Data are means ± s.e.m. (c, n = 3; d, n = 4). Asterisk indicates P 0.05, double asterisks indicate P 0.01 and dagger indicates P > 0.05 (t-test).",
    "ncbi_link": "IRGM: 345611
MFN1: 55669
MFN2: 9927"
  },
  {
    "caption": "(a) U937 cells were transfected with siRNA specific to FIS1, DRP1 or IRGM (or control oligonucleotides) as indicated, followed by plasmid encoding GFP-LC3. Autophagy was induced by treatment with hIFN-γ. GFP-LC3 puncta in cells were imaged by confocal microscopy. Scale bars, 5 μm. (b) LC3 puncta per cell were quantified from cells treated as in a.",
    "ncbi_link": "DRP1: 10059
FIS1: 51024
IRGM: 345611
LC3: 84557"
  },
  {
    "caption": "(c) U937 cells were transfected with siRNA specific to FIS1, DRP1 or IRGM (or control oligonucleotides) as indicated, followed by plasmid encoding GFP-LC3. Autophagy was induced by starvation. GFP-LC3 puncta in cells were imaged by confocal microscopy. Scale bars, 5 μm.",
    "ncbi_link": "DRP1: 10059
FIS1: 51024
IRGM: 345611
LC3: 84557"
  },
  {
    "caption": "(d) U937 cells were transfected with either control siRNA or siRNA specific to MFN1/MFN2, endogenous LC3 puncta per cell were quantified.",
    "ncbi_link": "MFN1: 55669
MFN2: 9927"
  },
  {
    "caption": "(b) HeLa cells were transfected with plasmids encoding fluorescent protein-tagged IRGMb, IRGMd WT (wild-type IRGMd) or IRGMS47N mutant (control cells; vector expressing GFP only), and after 48 h were labelled with MTR and imaged by live-cell confocal microscopy. Scale bars, 5 μm.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(c) Fluorescence intensity analysis of green and red channels along a line drawn through two adjacent cells, one GFP-IRGMd positive and one GFP-IRGMd negative, as indicated in the inset.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(g) Nitrocellulose filters spotted with the indicated lipids (defined in e) were incubated with wild-type IRGMd, IRGMdS47N, and the IRGM isoform IRGMb at the indicated concentrations. GST control is shown in Supplementary Information, Figure S1d. Membranes in e-g were probed with anti-GST antibody.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(a) HeLa cells transfected with plasmids encoding GFP or GFP-IRGMd were stained with MTR and imaged by live-cell confocal microscopy. Scale bars, 5 μm. (b-d) Quantification of mitochondrial morphologies in cells transfected with IRGMd, IRGMdS47N or IRGMb GFP fusions (control cells express GFP only).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(e)HeLa were transfected with the indicated siRNAs and vector encoding GFP-IRGMd, and labelled with MTR. The percentage of cells with mitochondrial morphologies ranging from normal, punctiform (dots) and elongated were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(f) HeLa were transfected with the indicated siRNAs and vector encoding GFP-IRGMd (or vector encoding GFP only, as a control) and labelled with MTR. Percentages of GFP+ cells with MTR staining at 48 h were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(g) Confocal microscopy images of HeLa cells transfected with vector encoding GFP-DRP1 (A) or GFP-IRGMd (B-G) and labelled with MTR (A-D) or antibodies against COX-IV (F). A, steady-state DRP1 distribution; B-D, translocation of IRGMd from the cytosol to mitochondria at indicated times post-transfection; E-G, co-localization of IRGMd and COX-IV (G is merged from E and F). Scale bars, 5 μm.",
    "ncbi_link": "DRP1: 10059
IRGM: 345611"
  },
  {
    "caption": "(h) HeLa cells, co-transfected with GFP-IRGMd, and control, BECN1 or ATG7 siRNA, were labelled with MTR 48 h post-transfection, imaged by live-cell microscopy, and percentages of GFP+ cells that were also MTR+ were quantified.",
    "ncbi_link": "ATG7: 10533
BECN1: 8678
IRGM: 345611"
  },
  {
    "caption": "(i) Cells from Atg7 wild-type (WT) or Atg7−/− MEFs transfected with vectors encoding GFP-IRGMd for 48 h were stained with MTR, imaged, and percentage of GFP+ cells that were also MTR+ cells was quantified.",
    "ncbi_link": "Atg7: 74244
IRGM: 15944"
  },
  {
    "caption": "(j) Wild-type W2 (Bax/Bak+/+) or mutant D3 (Bax/Bak−/−) BMK cells were transfected with vectors encoding GFP-IRGMd and after 48 h were labelled with MTR. Cells were imaged by live-cell microscopy, and percentages of GFP+ cells that were also MTR+ were quantified.",
    "ncbi_link": "Bak: 12018
Bax: 12028
IRGM: 15944"
  },
  {
    "caption": "(k) HeLa cells were transfected with vectors encoding GFP-IRGMd, treated with z-VAD as indicated, and after 48 h stained with MTR. Cells were imaged by live-cell microscopy, and percentages of GFP+ cells that were also MTR+ were quantified. Data are means ± s.e.m. (n = 3). Dagger indicates P ≥ 0.05, asterisk indicates P 0.05 and double asterisks indicate P 0.01 (t-test) for the indicated data.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(a) Percentage of HeLa cells transfected with vectors encoding GFP or GFP-IRGMd that were rounded 48 h post-transfection.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(b) HeLa cells transfected with plasmids encoding GFP or GFP-IRGMd were stained with 7-AAD after 48 h and percentages of GFP+ cells that were also 7-AAD+ were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(c) HeLa cells transfected with vectors encoding GFP-IRGMd versus GFP-IRGMdS47N and YFP-IRGMb (vector encoding GFP only was transfected as a control) were stained with 7-AAD after 48 h, and percentages of GFP+ (for IRGMd and IRGMS47N) or YFP+ (for IRGMb) cells that were also 7-AAD+ were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(d) HeLa cells were transfected with plamsids encoding GFP-IRGMd, GFP-IRGMDS47N or YFP-IRGMb (vector encoding GFP only was transfected as a control), and after 48 h were stained with propidium iodide (PI). Percentages of GFP+ or YFP+ cells that were also PI+ were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(e) Images of HeLa cells transfected with vectors encoding GFP-IRGMd (bottom) were stained for active caspases 3 and 7 using FLICA dye. Staurosporine (STS; middle images) was used as a positive control. Cells were transfected with vectors encoding GFP only as a control (top).",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(f) HeLa cells were transfected with plasmids encoding GFP-IRGMd and were stained with antibodies against HMGB1 (absence of nuclear HMGB1 stain is a marker of HMGB1 release) or DAPI. Top: images indicate GFP-IRGMd (left), HMGB1 (middle) and DAPI (right) localization. Bottom: phase-contrast microscopy image of cells (left) and image merged from other panels (right). Scale bars, 5 μm.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "(g-i) Cells were transfected with plasmids encoding GFP or GFP-IRGMd, and control or DRP1 siRNA, as indicated. After 48 h, (g) cells were stained with 7-AAD and percentages of GFP+ cells that were also 7-AAD+ were quantified, (h) rounded cells were quantified, or (i) cells were stained with HMGB1 and HMGB1+ nuclei were quantified. Data are means ± s.e.m. (n = 3). Asterisk indicates P 0.05 and double asterisk indicate P 0.01 (t-test).",
    "ncbi_link": "DRP1: 10059
IRGM: 345611"
  },
  {
    "caption": "(a, b) HeLa cells were transfected with plasmids encoding GFP, CFP-IRGMa, GFP-IRGMc or GFP-IRGMd, and after 24 h (a) or 48 h (b), stained with MTR. Percentages of positively transfected cells that were also MTR+ were then quantified. (c, d) Cells were transfected as in a, b, and after 24 h (c) or 48 h (d) the percentages of positively transfected cells that were also rounded by morphology were quantified.",
    "ncbi_link": "IRGM: 345611"
  },
  {
    "caption": "A-D. Example expression patterns for select genes identified by applying a general linear model (glm) including state, genotype, and interaction terms. Dots represent individual biological replicates (N = 3); lines highlight changes in mean values for replicates between each state (log2FC >1 and FDR < 0.05). A. State dependent expression is exemplified by Nanog which showed no difference between strains. B. Expression of Zfp277 exemplifies strain-dependence being consistently higher in B6. C & D. A significant genotype x state (GXS) interaction was identified for Nr5a2 (C, a marker for pluripotency) and Sox1 (D, a marker for neuronal differentiation).",
    "ncbi_link": "Nanog: 71950
Nr5a2: 26424
Sox1: 20664
Zfp277: 246196"
  },
  {
    "caption": "G. Coverage profile for Gstp2 locus on Chr 19 showing H3K4me3, ATAC, and RNA read depth from merged replicates. Locations of Chr 7 trans caQTL targets are indicated with black bars and LOD scores listed below.",
    "ncbi_link": "Gstp2: 14869"
  },
  {
    "caption": "F. Left - Coverage profiles (averaged biological replicates, N=3) for ChIP factor occupancy at Cd59a on Chr 2 under trans-regulation by the Chr 13d QTL. Distal ca-QTL target region used for quantification is indicated by a black box with LOD score below. Right - Scatterplots for ChIP factors comparing quantitative level of modification/binding for independent replicates between B6 and D2 ESCs.",
    "ncbi_link": "Cd59a: 12509"
  },
  {
    "caption": "I. Similar to F, coverage profiles for ChIP factor occupancy for a putative regulatory element on Chr 5 near Zfp932, targeted by Chr 12 trans caQTL, showed greater occupancy of POU5F1 and increased open chromatin compared to D2. Distal ca-QTL target region used for quantification is indicated by a black box with LOD score below.",
    "ncbi_link": "Zfp932: 69504"
  },
  {
    "caption": "A. Coverage profile for H3K4me3, ATAC, P300, and TRIM28 ChIP at a target locus for the QTL on Chr 4 for both chromatin accessibility (black boxes) and gene expression (Riok3 and Rmc1). LOD scores are listed under each target locus.",
    "ncbi_link": "Riok3: 66878
Rmc1: 76482"
  },
  {
    "caption": "(A-C) Atg5 KO MEFs were either untreated (NT) or starved (ST) with EBSS (Earle's Balanced Salt Solution) for 30 min. Total membranes (mem) from lysed cells were collected and incubated in a lipidation reaction with cytosols prepared from starved HEK293T cells. Reactions contained the indicated concentrations of PI3K inhibitor (PI3KI) 3-methyladenine (3-MA) (B) or FYVE protein (C). A diagram of the experimental scheme is shown in (A). RPN1, Ribophorin 1",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(D, E) Atg5 KO MEFs were either untreated (NT) or starved (ST) with EBSS in the absence or presence of 20 nM wortmannin (Wtm) or 10 mM 3-methyladenine (3-MA) for 30 min. Membranes from each treated cell sample were collected and subjected to a differential centrifugation to separate the 3K ×g, 25K ×g and 100K ×g pellet fractions followed by a lipidation assay as above (E). A diagram is shown in (D).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(F, G) Atg5 KO MEFs were starved for 30 min. Membranes in the 25K ×g and 100K ×g pellets from a differential centrifugation were collected as described above. A similar lipidation assay was performed in the presence of indicated concentrations (Conc in G) of 3-MA, wortmannin (F) and FYVE protein as well as a PI3P binding-deficient FYVE mutant protein (C/S) (G). Quantification of lipidation activity is shown as the ratio of LC3-II to LC3-I (II/I).",
    "ncbi_link": "Atg5: 11793
FYVE: 57590///53349"
  },
  {
    "caption": "(B) A small vesicle generation assay as above was performed with the indicated conditions. Slowly-sedimenting vesicles were collected to determine activity in the LC3 lipidation reaction. 3-MA, 5 mM; Wortmannin, 20 nM; S, starved Atg5 KO MEF cytosol; N, untreated Atg5 KO MEF cytosol; −/AP, in the absence of ATP regeneration and GTP and in the presence of apyrase (AP).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(F) A small vesicle generation assay as shown in (A) was performed with cytosols from starved Atg5 KO MEF from control or Sec23A knockdown cells in the absence or presence of Sar1A (H79G) or 3-MA followed by a lipidation reaction.",
    "ncbi_link": "Atg5: 11793///11793
Sec23A: 20334"
  },
  {
    "caption": "(G) Atg5 KO MEFs were starved for 30 min. Differential centrifugation as shown in Figure 1D was performed to collect the 25K ×g and 100K ×g pellet fractions. The LC3 lipidation was performed on these two fractions with indicated concentrations of SAR1 (H79G). Quantification of lipidation activity is shown as the ratio of LC3-II to LC3-I (II/I).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(A) Atg5 KO MEFs were either untreated or starved with or without 20 nM wortmannin for 30 min. Cells were harvested and ERGIC membranes were isolated by pooling fractions 3 and 4 (F2 in Figure 2C,D) of the OptiPrep gradient in the three-step fractionation approach followed by immunoblot to examine the amount of indicated markers on ERGIC membranes.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(B) Atg5 KO MEFs were transfected with a plasmid encoding an HA-tagged SEC31A. After transfection (24 hr), the cells were treated as shown in (A). Immunofluorescence was performed with anti-ERGIC53 and anti-HA antibodies and the cells were examined by confocal microscopy. Bar: 10 μM (C) Quantification of SEC31A overlapped with ERGIC53 shown in (B) using the Pearson's correlation coefficient (PCC). Error bars represent standard deviations from ∼20 cells in three independent experiments. p values were calculated by T-test.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "A The PA synthesis defective mutants pldα1 pldδ-1 and pldα1 pldδ-2 are salt-sensitive. Six-d-old seedlings were grown in half-strength Murashige and Skoog (MS), and then transferred to half-strength MS medium with or without 100 mM NaCl for 7 d.",
    "ncbi_link": "pldα1: 820816
pldδ: 829733"
  },
  {
    "caption": "G, H Analysis of the average values of the net Na+ (G) and K+ (H) fluxes of Col-0, sos2, C-1 and C-2. Six-d-old seedlings were treated with or without 50 mM NaCl for 24 h. Error bars represent SD (n ≥ 3).",
    "ncbi_link": "sos2: 833502"
  },
  {
    "caption": "I-N The contents of shoot Na+ (I), shoot K+ (J), root Na+ (K) and root K+ (L) as well as the relative ratios of shoot Na+/K+ (M) and root Na+/K+ (N) of Col-0 and pldα1 pldδ mutants. Six-d-old seedlings were transferred to half-strength MS medium with or without 100 mM NaCl treatment for 7 d. Error bars represent SEM of three independent biological repeats. O-T The contents of shoot Na+ (O), shoot K+ (P), root Na+ (Q) and root K+ (R) as well as the relative ratios of shoot Na+/K+ (S) and root Na+/K+ (T) of Col-0, sos2, C-1 and C-2 mutants. Six-d-old seedlings were transferred to half-strength MS medium with or without 50 mM NaCl treatment for 7 d. Error bars represent SEM of three independent biological repeats. D",
    "ncbi_link": "pldα1: 820816
pldδ: 829733
sos2: 833502"
  },
  {
    "caption": "C PA promotes the activity of SOS2 under salt stress. Ten-d-old transgenic plants expressing 35S:6×Myc-SOS2 in Col-0 or pldα1 pldδ-1 background were treated with or without 100 mM NaCl or 50 μM PA for 12 h. The total protein was extracted and immunoprecipitated with anti-Myc antibody-conjugated agarose, and then the purified Myc-SOS2 proteins at similar protein levels were incubated with His-SCaBP8 in the kinase assays. His-SCaBP8 was used as a specific substrate of SOS2. The numbers below the blots indicate the relative ratios of the signal intensity between the autoradiograph and Myc-SOS2 bands (Autorad/Myc). Statistical analysis of the relative ratios is shown D PA promotes the PM localization of SOS2 under salt stress. Ten-d-old seedlings were treated as described in Fig 3C. GHR1 was used as a plasma membrane marker. PEPC was used as a cytoplasm marker. The numbers represent the relative ratios of the signal intensity between Myc-SOS2 and GHR1 bands (Myc/GHR1). Statistical analysis of the relative ratios is shown",
    "ncbi_link": "Myc: 
pldα1: 820816
pldδ: 829733
SOS2: 833502"
  },
  {
    "caption": "D SOS2K57G has weak activity and cannot be activated by PA under salt stress. Ten-d-old seedlings expressing 35S:6×Myc-SOS2 or 35S:6×Myc-SOS2K57G in Col-0 or pldα1 pldδ-1 background were treated with or without 100 mM NaCl for 12 h. The brightness and contrast (B&C) of the autoradiograph was adjusted to clearly show the activity of SOS2K57G. The numbers below the blots indicate the relative ratios of the signal intensity between the autoradiograph and Myc-SOS2 bands (Autorad/Myc). Statistical analysis of the relative ratios is shown",
    "ncbi_link": "Myc: 
pldα1: 820816
pldδ: 829733
SOS2: 833502"
  },
  {
    "caption": "A The loss-of-function mutants akt1-1 and akt1-2 are salt-sensitive. Six-d-old seedlings of Col-0 (WT) and akt1 mutants were treated with or without 100 mM NaCl for 7 d. B Analysis for primary root length, related to Fig 5A. Data was shown in a box and whiskers (min to max) form (n ≥ 10). Statistical analysis was done by two-way ANOVA with Holm-Sidak's multiple comparisons test (P ≤ 0.05). C",
    "ncbi_link": "akt1: "
  },
  {
    "caption": "C, D Analysis of the average values of the net Na+ (C) and K+ (D) fluxes of Col-0 and akt1 mutants with or without 100 mM NaCl treatment for 24 h. Error bars represent SD (n ≥ 4).",
    "ncbi_link": "akt1: "
  },
  {
    "caption": "K Time- and voltage-dependent AKT1-mediated K+ current recordings from oocytes. Whole-cell K+ currents were recorded in oocytes that were co-injected with indicated mixture of cRNAs for AKT1, SCaBP8 and SOS2 (SOS2WT or SOS2K57G), in the presence of CIPK23 and CBL1. 30% SOS2 means that the cRNA injection amount of SOS2 was 30% of SCaBP8. The oocytes were treated with or without 50 μM PA for 1.5 h.",
    "ncbi_link": "AKT1: 
SCaBP8: 
CBL1: 827481
CIPK23: 839907
SOS2: 833502"
  },
  {
    "caption": "D SOS2K40N and SOS2T168D∆FISL attenuate the SCaBP8-mediated inhibition of AKT1 in oocytes. The recorded oocytes were co-injected with indicated mixture of cRNAs for AKT1, SCaBP8 and SOS2 (SOS2WT, SOS2T168D∆FISL or SOS2K40N) in the presence of CIPK23 and CBL1.",
    "ncbi_link": "AKT1: 
SCaBP8: 
SOS2: 833502"
  },
  {
    "caption": "E I-V relationship of AKT1 steady-state currents in oocytes. Error bars represent SD (n ≥ 7).",
    "ncbi_link": "AKT1: "
  },
  {
    "caption": "(B) Dot-plot showing the fold change (log2) in number of reads between vehicle and AZD8186-treated conditions vs the p-value of the difference between the two treatment conditions for each shRNA. 9 out of 18 shRNAs targeting EGFR showed a p-value <0.2 and are highlighted in the plot. The plot was generated considering the results from biological triplicate of the experiment.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(C MDA-MB-468 were infected with the indicated shRNAs targeting EGFR and selected by puromycin. EGFR mRNA was then measured by RT-qPCR (C) Average ± SD of triplicates and representative of three independent experiments.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "D) MDA-MB-468 were infected with the indicated shRNAs targeting EGFR and selected by puromycin. cell viability was measured after 4 days of treatment with serial dilutions of AZD8186 (D). Average ± SD of triplicates and representative of three independent experiments.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "(G) Viability of six PTEN-null VS five PTEN-WT TNBC cell lines - not carrying other known mutations in PIK3CA, PIK3CB or PIK3R1 genes - treated with PI3Kβi (AZD8186 90 nM), EGFRi (gefitinib 3 μM) alone or in combination for 6 days. Mean of 3 independent experiments ± SD. Statistical significance of two-tailed unpaired student t-test in PTEN-null PI3Kbi versus PI3Kbi+EGFRi **P=0.0059, PTEN-null EGFRi versus PI3Kbi+EGFRi **P=0.0047, PTEN-null PI3Kbi+EGFRi versus PTEN-WT PI3Kbi+EGFRi *P=0.0459, PTEN-WT PI3Kbi versus PI3Kbi+EGFRi *P=0.0108, PTEN-WT EGFRi versus PI3Kbi+EGFRi n.s. P=0.1926. PTEN-null cell lines used in the experiments were: MDA-MB-468, HCC70, HCC1937, HCC38, HCC1395 and BT-549; PTEN-WT cell lines were: MDA-MB-157, MDA-MB-231, HCC1187, HCC1428 and HCC1806.",
    "ncbi_link": "PIK3CA: 5290
PIK3CB: 5291
PIK3R1: 5295
PTEN: 5728"
  },
  {
    "caption": "(H) Synergy score for combinations of serial dilutions of PI3Kβi (AZD8186) plus EGFRi (gefitinib) tested on six PTEN-null and five PTEN-WT TNBC cell lines for 6 days in three independent experiments. The score was obtained analysing the viability data through the software Chalice Analyser. Mean of the synergy scores ± SD. Statistical significance of Mann Whitney two-tailed test *P=0.0303.",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "(I) Patient samples from METABRIC dataset classified as TNBCs were assigned to the groups \"PTEN-low\" when falling in the lower quartile for PTEN expression, \"PTEN-mut\" when harbouring a non-synonymous mutation on PTEN gene, \"PTEN-WT\" in all other cases. Comparison of the expression of EGFR between the PTEN low or mut and the PTEN-WT groups. Data presented in a box and whisker plot with the central band indicating the median, the upper and lower extremes of the box or hinge being the third and first quartiles respectively and the whiskers extending to the most extreme data values Mean ± SD. P value calculated by unpaired t-test.",
    "ncbi_link": "EGFR: 1956
PTEN: 5728"
  },
  {
    "caption": "(E) A cell line derived from a mammary tumor spontaneously developed in a Wap-cre:Ptenfl/fl:Tp53fl/fl mouse was cloned and injected in the mammary fat pad of syngeneic C57BL6/J recipient mice. Tumours grew in 12 out of 35 transplanted mice and only these tumours were selected for the treatments described in the figure. When tumours reached an average volume of 100mm3, they were treated with vehicle or a combination of AZD8186 (150mg/kg, og once/day) and erlotinib (50mg/kg IP once/day). Tumours were then measured during the treatment (6 mice per group, mean±SEM). Statistical significance of two-way ANOVA statistical test ****P<0.0001.",
    "ncbi_link": "cre: 2777477
Pten: 5728
Tp53: 7157
Wap: 22373"
  },
  {
    "caption": "(A Results of CRISPR-Cas9 screening in combination with AZD8186 100nM (A) The dot-plots show for each gene knocked-out by sgRNAs the fold change (log2) between treated conditions (AZD8186 and vehicle in the fluorescence signal (anti-phosphoS6 immunofluorescence) versus the p-value of the difference calculated by two sided t-test. The plots represent means of biological triplicates. Genes for which it was calculated a p<0.0001 and Log2 (fold change)>0.25 are reported and highlighted in green; genes having a 0.0001 0.25 are reported and shown in red. Gefitinib combined with AZD8186 represents the positive control of the experiment (A). <0.05>",
    "ncbi_link": "Cas9: 2777477"
  },
  {
    "caption": "B) Results of CRISPR-Cas9 screening in combination with GDC0941 400nM (B). The dot-plots show for each gene knocked-out by sgRNAs the fold change (log2) between treated conditions GDC0941, and vehicle in the fluorescence signal (anti-phosphoS6 immunofluorescence) versus the p-value of the difference calculated by two sided t-test. The plots represent means of biological triplicates. Genes for which it was calculated a p<0.0001 and Log2 (fold change)>0.25 are reported and highlighted in green; genes having a 0.0001 0.25 are reported and shown in red. <0.05>",
    "ncbi_link": "Cas9: 2777477"
  },
  {
    "caption": "(C) Box & Whisker plot showing the fold change in fluorescence signal between vehicle and GDC0941-treated conditions for MDA-MB-468 cells transduced with non-target Control, GNB2 or GNG5 sgRNAs (N=2 or 3). Data presented in a box and whisker plot with the central band indicating the median, the upper and lower extremes of the box or hinge being the third and first quartiles respectively and the whiskers extending to the most extreme data values within 1.5 times the inter-quartile range. Statistical significance of unpaired t-test ****P<0.0001.",
    "ncbi_link": "GNB2: 2783
GNG5: 2787"
  },
  {
    "caption": "(D) Biochemical analysis of GNB2 KO cells. Cell lysates of MDA-MB-468 parental cells and three MDA-MB-468 GNB2 KO clones were probed with the indicated antibodies. Quantification of the bands was performed by ImageLite software.",
    "ncbi_link": "GNB2: 2783"
  },
  {
    "caption": "(A) MDA-MB-468 parental cells and three MDA-MB-468 GNB2 KO clones were treated with vehicle, GDC0941 1 μM, gefitinib 3 μM or lapatinib 1 μM for 24 hours. The cell lysates were probed with the indicated antibodies.",
    "ncbi_link": "GNB2: 2783"
  },
  {
    "caption": "(B-D) Viability assays of MDA-MB-468 parental cells and three MDA-MB-468 GNB2 KO clones treated with serial dilutions of the indicated drugs for six days. Mean ± SD of triplicates and representative of two or three independent experiments.",
    "ncbi_link": "GNB2: 2783"
  },
  {
    "caption": "(E) Patient samples from METABRIC dataset classified as TNBCs (N=299) were assigned to the groups \"PTEN-low\" when falling in the lower quartile for PTEN expression, \"PTEN-mut\" when harbouring a non-synonymous mutation on PTEN gene, \"PTEN-WT\" in all other cases. Comparison of the expression of GNB2 between the PTEN low or mut and the PTEN-WT groups. Box & Whisker plot (Median/IQR/1.5*IQR Whiskers). P value calculated by unpaired t-test.",
    "ncbi_link": "GNB2: 2783
PTEN: 5728"
  },
  {
    "caption": "(C) MDA-MB-468 parental cells or GNB2 KO clones were starved and treated with scramble or PAR1 activating peptide for 5 minutes, alone or in combination with vorapaxar. The cell lysates were probed with the indicated antibodies. Phospho-AKT, pan-AKT, phospho-ERK1/2 and pan-ERK1/2 bands were quantified by the use of ImageLite software: the ratio of phospho-AKT to pan-AKT and phospho-ERK1/2 to pan-ERK1/2 normalised to the control peptide-treated conditions for WT and GNB2 KO cells (first and forth lanes, respectively) is shown.",
    "ncbi_link": "GNB2: 2783"
  },
  {
    "caption": "(D) p-S6/loading control signal from western blots experiments in which a panel of six TNBC PTEN-null cell lines and HCC70 cells that acquired resistance to AZD8186 or MK2206 were treated with vehicle, vorapaxar (10 μM), GDC0941 (1 μM) or lapatinib (1 μM) alone or in the indicated combinations. The values were normalised to vehicle treatment for all cell lines. Mean of 2 independent experiments ± SD. P values calculated by two-tailed paired student t-test *P=0.0235 and **P=0.002. Cell lines used in the experiments were: MDA-MB-468, HCC70, HCC1937, HCC38, HCC1395, BT-549, HCC70 AZD8186-resistant and HCC70 MK2206-resistant.",
    "ncbi_link": "PTEN: 5728"
  },
  {
    "caption": "Data matrix showing frequent SCNVs, significantly mutated genes (bold; Benjamini-Hochberg FDR 0.2 calculated with CHASM) and their associated pathway or family mutations discovered in cases with NPC analyzed by WES, targeted deep sequencing (TS) or SNP array (SNP-a). The frequencies of the alterations are plotted on the right. The colors and shapes denoting different types of somatic events are also applied in Figure 5a. Columns, examined cases; rows, genes; hot spot, identical mutations have been registered in COSMIC (see URLs); LOH, loss of heterozygosity. The asterisk indicates that this tumor was also subjected to SNP array profiling. PIK3CA amplification in C666 cells has been previously described.",
    "ncbi_link": "PIK3CA: 5290"
  },
  {
    "caption": "(a-d) NPC cells stably expressing either negative control shRNA (Scramble) or pooled shRNAs targeting ARID1A (shARID1A) were subjected to anchorage-independent colony formation assay (a), migration assay (b), xenograft growth assay (horizontal lines, mean values) and western blot (WB) assay with the indicated antibodies (d).",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "(e-g) NPC cells either with or without exogenously expressing ARID1A were examined by anchorage-independent colony formation assay (e)",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "(e-g) NPC cells either with or without exogenously expressing ARID1A were examined by anchorage-independent colony formation assay (e), migration assay (f)",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "e-g) NPC cells either with or without exogenously expressing ARID1A were examined by anchorage-independent colony formation assay (e), migration assay (f) and WB assay with the indicated antibodies (g).",
    "ncbi_link": "ARID1A: 8289"
  },
  {
    "caption": "(h,i) NPC cells either with or without exogenously expressing BAP1 were examined by anchorage-independent colony formation assay (h)",
    "ncbi_link": "BAP1: 8314"
  },
  {
    "caption": "h,i) NPC cells either with or without exogenously expressing BAP1 were examined by anchorage-independent colony formation assay (h) and WB assay with indicated antibodies (i). β-actin was examined as a loading control. The data shown in a, b, e, f and h represent the mean ± s.d.; n = 3 for a, b, e and f; n = 4 for h. *P 0.05, **P 0.01. Student's t-test was used to calculate statistical significance in a-c, e, f and h; the blots shown in d, g and i are representative of three total blots run.",
    "ncbi_link": "BAP1: 8314"
  },
  {
    "caption": "(a) Data matrix showing alterations of genes involved in the ERBB-PI3K signaling pathway and their related targeting molecules. Considering space limitations, the numbers of targeting agents available for each protein are shown in parentheses. Drugs currently in phase 2 clinical trials are marked in blue, those in phase 3 are in purple, and FDA-approved drugs are in brown (see URLs).",
    "ncbi_link": "ERBB: 1956
PI3K: 5294///5293///5291///5290"
  },
  {
    "caption": "(b) Kaplan-Meier survival curves of NPC subjects either with or without genetic lesions in the ERBB-PI3K signaling pathway. Log-rank test was used to calculate statistical significance.",
    "ncbi_link": "ERBB: 1956
PI3K: 5294///5293///5291///5290"
  },
  {
    "caption": "(A) The expression of AR was determined using Western blots (overexpressing AR in J82 cells and knocking down AR in UMUC3 cells).",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(B) Relative expression of the top 20 up-regulated circRNAs from the GEO dataset GSE92675 (BCa tumor tissues compared to para-tumor tissues) in response to AR modulation in J82 and UMUC3 cells. The # indicates an RNA with a relatively low expression (qRT-PCR cycle number > 35), thus the circRNA was excluded for further analysis.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(E) Real-time quantitative PCR (qRT-PCR) results show the knock down efficiency for these 4 circRNAs in J82 oe-AR (J82-AR) cells.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(F) Transwell invasion assays showed that knock down of hsa_circ_0084171 (circ_oo84171), but not the other circRNAs, can partly reverse oeAR-increased invasion in J82 cells. Scale bar, 100 μm.",
    "ncbi_link": "circ_oo84171: 
hsa_circ_0084171: 
AR: 367"
  },
  {
    "caption": "(G) MTT assays showed that shcirc_0084171 can partly reverse oeAR-increased cisplatin chemo-resistance (2 μg/ml) in J82 cells. To calculate the mean, the value of 0 µg/ml cisplatin groups were set as 1.",
    "ncbi_link": "circ_0084171: 
AR: 367"
  },
  {
    "caption": "(H) The qRT-PCR results showed that the overexpression (oe) efficacy for hsa_circ_0084171 (oecirc_0084171) in UMUC3-shAR cells.",
    "ncbi_link": "circ_0084171: 
hsa_circ_0084171: 
AR: 367"
  },
  {
    "caption": "(I) Transwell invasion assays showed that oecirc_0084171 can partly rescue shAR induced invasion deduction in UMUC3 cells. Scale bar, 100 μm.",
    "ncbi_link": "circ_0084171: 
AR: 367"
  },
  {
    "caption": "(J) MTT assays showed that oecirc_0084171 can partly overcome shAR effect for cisplatin chemo-resistance (2 μg/ml) in UMUC3 cells.",
    "ncbi_link": "circ_0084171: 
AR: 367"
  },
  {
    "caption": "B) The relative expression of circFNTA was elevated in multiple BCa cell lines (T24, J82, UMUC3, and 5637) compared to normal bladder epithelial cell line SVHUC as shown by qRT-PCR.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "C) The expression of circFNTA and GAPDH mRNA in J82 and UMUC3 cells treated with or without RNase R was detected by qRT-PCR.",
    "ncbi_link": "circFNTA: 
GAPDH: "
  },
  {
    "caption": "D) RNA Fluorescence in situ hybridization (FISH) demonstrated that circFNTA was predominantly localized to the cytoplasm of J82 and UMUC3 cells. DAPI was mainly localized to the cytoplasm. Scale bar, 20 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "E) Two shcircFNTA plasmids using PLKO.1 vector were transfected into UMUC3 cells. The knock down efficacy was measured by qRT-PCR.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "G) The qRT-PCR results show oecircFNTA efficacy in J82 cells compared with PWPI vector (left panel) and oecircFNTA or oelinearFNTA in J82 cells (right panel).",
    "ncbi_link": "circFNTA: 
linearFNTA: "
  },
  {
    "caption": "Transwell invasion assays showed that shcircFNTA can decrease UMUC3 cell invasion (H) more profoundly than oelinearFNTA as compared with the oevector group. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "Transwell invasion assays showed that shcircFNTA can increase J82 cells invasion (I) more profoundly than oelinearFNTA as compared with the oevector group. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: 
linearFNTA: "
  },
  {
    "caption": "J) MTT assays showed that oecircFNTA enhances J82 cells chemo-resistance to cisplatin (0, 1, 2, 5, 10 μg/ml were tested). This effect was more obvious in the oecircFNTA group as in the oelinearFNTA group (upper panel). MTT assays showed that shcircFNTA increases UMUC3 cells chemo-sensitivity to cisplatin (lower panel).",
    "ncbi_link": "circFNTA: 
linearFNTA: "
  },
  {
    "caption": "K) FISH analyses revealed that circFNTA was significantly upregulated in BCa tissues as compared with the adjacent para-tumor tissues (N=41 patients) and representative images are shown. Scale bar, 250 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "L) The qRT-PCR assays also demonstrated that circFNTA is significantly elevated in fresh BCa tissues compared to para-tumor tissues (N=23 patients).",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(A) The protein expression of AR and FNTA (circFNTA host gene) were determined using Western blot and showed that shAR can decrease FNTA protein expression in UMUC3 cells and oeAR can increase FNTA protein expression in J82 cells.",
    "ncbi_link": "circFNTA: 
AR: 367"
  },
  {
    "caption": "(B) qRT-PCR results showed that mRNA levels of FNTA are not changed dramatically in UMUC3 cells with shAR and J82 cells with oeAR.",
    "ncbi_link": "AR: 367
FNTA: 2339"
  },
  {
    "caption": "(C) The mRNA levels of 4 RNA editing genes (ADAR, ADAR2, DHX9, and QKI) were tested with manipulated AR (UMUC3 cells in left panel and J82 cells in right panel). Results showed ADAR2 mRNA is negatively correlated with AR expression.",
    "ncbi_link": "ADAR: 103
ADAR2: 104
AR: 367
DHX9: 1660
QKI: 9444"
  },
  {
    "caption": "(D) Western blot analysis also confirmed that ADAR2 can be negatively regulated by AR at the protein level.",
    "ncbi_link": "AR: 367"
  },
  {
    "caption": "(E) Knock down efficiency of AR and ADAR2 (shADAR2#1 and shADAR#2) in UMUC3 cells, as determined by qRT-PCR.",
    "ncbi_link": "ADAR2: 104
AR: 367"
  },
  {
    "caption": "(F) shADAR2#1 and shADAR#2 could both reverse shAR-dependent circFNTA reduction in UMUC3 cells.",
    "ncbi_link": "circFNTA: 
ADAR2: 104
AR: 367"
  },
  {
    "caption": "(G) Transwell invasion assays confirmed that both shADAR2 constructs can partly reverse shAR-dependent UMUC3 cells invasion reduction. Scale bar, 100 μm.",
    "ncbi_link": "ADAR2: 104
AR: 367"
  },
  {
    "caption": "(H) MTT assays confirmed that both shADAR2 constructs can partly overcome shAR-dependent effects on cisplatin chemo-resistance (2 μg/ml) in UMUC3 cells.",
    "ncbi_link": "ADAR2: 104
AR: 367"
  },
  {
    "caption": "(J) ChIP assays confirmed that AR can directly bind to ADAR2 AREI/II (-572nt to -555nt).",
    "ncbi_link": "ADAR2: 104"
  },
  {
    "caption": "(M) Co-transfection of ARE Wild type (WT) or Mutant (Mut) ADAR2 promoter pGL3-Luciferase constructs into UMUC3 cells with/without shAR (left panel), and J82 cells with/without oeAR (right panel). The luciferase assay was used to detect promoter activity.",
    "ncbi_link": "Luciferase: 
ADAR2: 104
AR: 367"
  },
  {
    "caption": "(A) Western blot analysis showed that shcircFNTA can decrease FNTA expression in UMUC3 cells (upper panel) and oecircFNTA can increase FNTA expression, and that this was more profound than using oelinearFNTA in J82 cells (lower panel).",
    "ncbi_link": "circFNTA: 
linearFNTA: "
  },
  {
    "caption": "(B) A RNA pull-down assay was used to test the binding of circFNTA to 11 miRNAs (predicted by online database) in UMUC3 cells. The results showed that miR-328-5p, miR-370-3p and miR-920 can be pulled-down by circFNTA.",
    "ncbi_link": "circFNTA: 
miR-328-5p: RF00772
miR-370-3p: RF00740
miR-920: RF00986"
  },
  {
    "caption": "Transwell invasion assay (D) confirmed that only oemiR-370-3p can reverse oecircFNTA induced invasion in J82 cells,",
    "ncbi_link": "circFNTA: 
miR-370-3p: RF00740"
  },
  {
    "caption": "MTT assays (E) confirmed that oemiR-370-3p can reverse oecircFNTA induced cisplatin chemo-resistance (2 μg/ml) in J82 cells. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: 
miR-370-3p: RF00740"
  },
  {
    "caption": "Transducing the miR-370-3p inhibitor into UMUC3 cells can reverse FNTA protein reduction by shcircFNTA shown by Western blot (F)",
    "ncbi_link": "circFNTA: 
miR-370-3p: RF00740"
  },
  {
    "caption": "Transducing the miR-370-3p inhibitor into UMUC3 cells can reverse FNTA protein reduction by shcircFNTA shown by Transwell assay (G).",
    "ncbi_link": "circFNTA: 
miR-370-3p: RF00740"
  },
  {
    "caption": "(H) MTT assays also confirmed that transducing with a miR-370-3p inhibitor in UMUC3 cells can partly reverse cisplatin chemo-resistance (2 μg/ml) reduction by shcircFNTA.",
    "ncbi_link": "circFNTA: 
miR-370-3p: RF00740"
  },
  {
    "caption": "(J) The transfection efficacy of oecircFNTA WT and oecircFNTA Mut was tested by qRT-PCR.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(K) Transfection with oecircFNTA WT could increase J82 cells invasion, while oecircFNTA Mut cannot. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(L) Tramsfection with oecircFNTA WT could increase J82 cells cisplatin chemo-resistance (2 μg/ml), while oecircFNTA Mut did not have this effect.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(N) Luciferase reporter activity after transfection of WT and Mut FNTA 3'UTR reporter constructs into UMUC3 cells (left panel), comparing transduced miR-370-3p inhibitor vs Ctrl and J82 cells (right panel), and comparing oemiR-370-3p vs control PLV.",
    "ncbi_link": "FNTA: 2339
miR-370-3p: RF00740"
  },
  {
    "caption": "(A) Western blots show the knock-down efficiency of shFNTA in J82 and UMUC3 cells.",
    "ncbi_link": "FNTA: 2339"
  },
  {
    "caption": "(B) Transwell assays indicated that shFNTA can partly reverse oecircFNTA-increased invasion in J82 and UMUC3 cells. Quantifications are shown on the right. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: 
FNTA: 2339"
  },
  {
    "caption": "(C) MTT assays also confirmed that shFNTA can reverse oecircFNTA-increased chemo-resistance to cisplatin (2 μg/ml) in J82 and UMUC3 cells.",
    "ncbi_link": "circFNTA: 
FNTA: 2339"
  },
  {
    "caption": "Transwell assays (D, with quantitations at the right) indicated that treatment with Tipifarnib (farnesyltransferase inhibitor) can partly reverse oecircFNTA-increased invasion in J82 and UMUC3 cells. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "MTT assays (E) indicated that treatment with Tipifarnib (farnesyltransferase inhibitor) can partly reverse oecircFNTA-increased invasion in J82 and UMUC3 cells. Scale bar, 100 μm.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(F) Western blots showed that shcircFNTA in UMUC3 or oecircFNTA in J82 cells did not change KRAS protein level significantly.",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(G) Raf-1 RBD GST-pull-down assays confirmed that shcircFNTA can decease KRAS activity in UMUC3 cells (upper panel), and oecircFNTA can increase KRAS activity in J82 cells (lower panel).",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(H) Western blots showed that shcircFNTA can decrease ERK1/2 and MEK1/2 phosphorylation in UMUC3 cells (left panel), and oecircFNTA can increase their phosphorylation in J82 cells (right panel).",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(A) UMUC3-PLKO and UMUC3-shcircFNTA cells were used to establish a subcutaneous nude mouse xenograft model, and cisplatin (1 mg/kg) was intraperitoneally administered. Images of tumors are shown after mice were sacrificed (N= 6). (B) Compared with the vector (PLKO) group, the tumor growth rate was significantly inhibited in shcircFNTA nude mice. (C) Tumor weights also decreased in the shcircFNTA group. ",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(D-E) The qRT-PCR results using mouse tumor tissues revealed that circFNTA expression was significantly reduced (D), and the expression of its host gene FNTA was correspondently decreased in the shcircFNTA group as compared to the PLKO group (E).",
    "ncbi_link": "circFNTA: 
FNTA: 2339"
  },
  {
    "caption": "(F) Representative immunohistochemistry (IHC) images detecting FNTA, p-ERK1/2 and p-MEK1/2 in PLKO tumurs as compared to shcircFNTA xenografted tumors. Scale bars: 100 μm (upper panels) and 25 μm (lower panels). (G) Quantification of relative IHC staining intensity revealed that targeting circFNTA led to decreased expression of FNTA, p-ERK1/2 and p-MEK1/2. ",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "(H) The tumor tail vein injection model was established to observe lung metastasis (N=6). Representative images of lung metastasis foci in gross and microscopic HE examination. Scale bars: 400 μm (upper panels) and 100 μm (lower panels). (I) Knocking down circFNTA significantly decreased metastatic foci numbers as compared to the PLKO group. (J) Targeting circFNTA significantly reduced lung metastatic foci as compared to the PLKO group. ",
    "ncbi_link": "circFNTA: "
  },
  {
    "caption": "C. Interaction  between PIF7  and ASF1A/ASF1B  was detected using a semi-in vivo pull-down assay. GST-ASF1A/ASF1B  were purified from E. coli. PIF7-Flash  protein from overexpressing PIF7-Flash seedlings  grown under white light  or 1 h of shade  treatment was detected using an anti-MYC  antibody.",
    "ncbi_link": "PIF7: 836248"
  },
  {
    "caption": "F. Interactions  between ASF1A  and PIF7/HIRA  were detected in tobacco leaf  cells. The PIF7-Flash, HIRA-HA, and GFP-ASF1A  (GFP  as control) proteins were co-expressed in tobacco leaf  cells. Anti-GFP Sepharose  beads were used for Co-IP assay.",
    "ncbi_link": "Flash: 
GFP: 
HA: 
HIRA: 823578
PIF7: 836248
ASF1A: 842992"
  },
  {
    "caption": "B, Growth  analysis of  Col-0, pif7-1, asf1ab, and hira-1 seedlings  treated with shade. New hypocotyl growth  and real-time growth  rates were recorded at 15-min intervals after shade  treatment.",
    "ncbi_link": "hira: 823578
pif7: 836248
asf1a: 842992"
  },
  {
    "caption": "D. Hypocotyl  lengths of Col-0, phyB-9, asf1ab, phyB-9  *   asf1ab,  hira-1, and  phyB-9 * hira-1  grown under white light. The scale bar represents 2 mm. Different letters indicate significant differences (P < 0.01) calculated using one-way ANOVA with Tukey's HSD test. At least 20 seedlings  were used for each treatment or genotype. E. Hypocotyl  lengths of Col-0, pif7-1, asf1ab,  pif7-1 *  asf1ab, hira-1, and  pif7-1 * hira-1 under white light and shade  conditions. The scale bar represents 2 mm. Different letters indicate significant differences (P < 0.01) calculated using one-way ANOVA with Tukey's HSD test. At least 20 seedlings were used for each treatment or genotype.",
    "ncbi_link": "hira: 823578
phyB: 816394
pif7: 836248
asf1a: 842992"
  },
  {
    "caption": "B. Boxplot displays the fold changes in shade-induced genes in Col-0, pif7-1, asf1ab, and hira-1 by comparing the transcript levels between  white light  and shade  conditions. Different letters indicate significant differences (P < 0.05) as determined by one-way ANOVA.",
    "ncbi_link": "hira: 823578
pif7: 836248
asf1a: 842992"
  },
  {
    "caption": "D. Integrative genomics viewer (IGV) screenshots showing the distribution of GFP-ASF1A  enrichment at the ATHB2, PIN7, CSLC4, BIM1, ARL, and NPY8  loci.",
    "ncbi_link": "NPY8: 
ARL: 819014
BIM1: 830708
CSLC4: 822444
HB2: 820216
PIN7: 838916"
  },
  {
    "caption": "G. ChIP-PCR  analysis of ASF1  enrichment using anti-ASF1A  antibodies at the ATHB2, PIN7, CSLC4, BIM1, ARL, and NPY8  loci. Col-0 and pif7-1 seedlings  were grown under continuous  white light or transferred to the shade  for 1 h. Top panels show a schematic representation of the gene structures. The bottom panels represent the effects of shade  on ASF1A  enrichment. Shade-increased enrichment of ASF1A  was calculated as input% SH  minus input% WL. The difference at the P2 locus in Col-0 was normalized to one for each gene. Different letters indicate statistically significant differences (P < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, where n refers to technical replicates).",
    "ncbi_link": "NPY8: 
ARL: 819014
BIM1: 830708
CSLC4: 822444
HB2: 820216
pif7: 836248
PIN7: 838916"
  },
  {
    "caption": "G. IGV screenshots show the distribution of H3.3  and H3.1  enrichment levels at the ATHB2, PIN7, CSLC4, BIM1, ARL, and NPY8  loci.",
    "ncbi_link": "NPY8: 
ARL: 819014
BIM1: 830708
CSLC4: 822444
HB2: 820216
PIN7: 838916"
  },
  {
    "caption": "H. Hypocotyl  lengths of Col-0, pif7-1, and h3.3kd under white light and shade  conditions. The scale bar represents 2 mm. Different letters indicate significant differences (P < 0.01) calculated using one-way ANOVA with Tukey's HSD test. At least 20 seedlings  were used for each treatment or genotype.",
    "ncbi_link": "h3.3: 830164
pif7: 836248"
  },
  {
    "caption": "I. Relative expression  levels of ATHB2, PIN7, CSLC4, BIM1, ARL, and NPY8  in Col-0, pif7-1, and  h3.3kd seedlings  grown under white light  or shade  conditions. The seedlings  were grown under  white light  for 6 d, and then maintained under  white light, or transferred to shade  for 1 h. Different letters indicate statistically significant differences (P < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the mean ± SDs (n = 3, n refers to biological replicates).",
    "ncbi_link": "NPY8: 
ARL: 819014
h3.3: 830164
BIM1: 830708
CSLC4: 822444
HB2: 820216
pif7: 836248
PIN7: 838916"
  },
  {
    "caption": "E. ChIP-PCR  analysis of HTR5  (H3.3) levels at the ATHB2, PIN7, CSLC4, BIM1, ARL, and NPY8  loci. Top panels show a schematic representation of the gene structures. The bottom panels represent the effects of shade  on H3.3 enrichment. Shade-increased enrichment of H3.3  was calculated as the input% SH  minus input% WL. The difference at the P2 locus in Col-0 was normalized to one for each gene. Different letters indicate statistically significant differences (P < 0.05) by one-way ANOVA with Tukey's HSD test. The data shown are the means ± SDs (n = 3, where n refers to biological replicates).",
    "ncbi_link": "NPY8: 
ARL: 819014
BIM1: 830708
CSLC4: 822444
HB2: 820216
PIN7: 838916"
  },
  {
    "caption": "(E) Top, Representative images of live HeLa  cells in cytokinesis transiently transfected with GFP-CENP-E2605-2701 and mutants (green), incubated with SiR-tubulin  (red). Scale bar, 10μm. Bottom, linescans showing the fluorescence intensity average and standard error of the mean (SEM) for the GFP-CENP-E2605-2701 and mutants and tubulin  across the cell midbody. For GFP-CENP-E2605-2701, n is the number of cells. n=11 and for the GFP-CENP-E2605-2701 mutants FDN2661LTT, YF2660AA, FF2644AA, n= 15, 16 and 25 respectively. Biological independent replicates were respectively 2, 3, 2 and 1.",
    "ncbi_link": "GFP: 
CENP-E: 1062"
  },
  {
    "caption": "(B) Representative images of live HeLa  cells in mitosis transiently transfected with either GFP-Kif4A1133-1165 or GFP-Kif4A1133-1232 incubated with SiR-Tubulin. Scale bar, 10μm. Quantification of cells with GFP-Kif4A1133-1165 (n=12) or GFP-Kif4A1133-1232 (n=13) localization  to the  central spindle. Data represented from 2 independent experiments.",
    "ncbi_link": "GFP: 
Kif4A: 24137"
  },
  {
    "caption": "(D) Live-cell imaging of  metaphase spindles in HeLa  cells transiently transfected wild-type, phosphomimetic and non-phosphorylatable mutants of GFP-CENP-E2605-2701 (monomeric) and GFP-GST-CENP-E2605-2701 (dimeric) and stained  for tubulin  using SiR-Tubulin. The fraction of cells localizing  to the overlapping microtubules  is represented as a percentage. Scalebar, 10 μm.",
    "ncbi_link": "GFP: 
GST: 
CENP-E: 1062"
  },
  {
    "caption": "(G) Bar graph showing mean and standard error for GFP  fluorescence intensity at peak fluorescence for GFP-GST-CENP-E2605-2701 and mutants at 9.7μm, quantified in F. Asterisks indicate ordinary One-way Anova test significance value. ****P<0.0001.",
    "ncbi_link": "GFP: 
GST: 
CENP-E: 1062"
  },
  {
    "caption": "(A) Representative immunofluorescence  images of HeLa  cells in  late anaphase and telophase, expressing GFP-PRC1-WT or -MEE and depleted for endogenous PRC1  using a PRC1  siRNA and a PRC1  sgRNA after doxycycline-induced Cas 9 expression. Microtubules, GFP  and CENP-E are in white, green and red respectively. DNA  is in blue. (B) Graph showing the percentage of cells with a PRC1-localized  at the site of abscission for cells treated in (A). Mean and standard deviation are presented, n= 156 and 141 for cells expressing PRC1-WT and -MEE respectively. Data from 4 biological replicates and 1 technical replicate. Asterisks indicate a T-test significance value. ****P<0.0001. (C) Graph showing the percentage of cells with CENP-E localized  at the abscission site for cells treated in (A), mean and standard deviation are presented, n= 58 and 66 for cells expressing PRC1-WT and -MEE respectively. Data from 2 biological replicates. p-value (p=0.11) calculated for an unpaired T-test.",
    "ncbi_link": "GFP: 
Cas 9: 69900935
PRC1: 9055"
  },
  {
    "caption": "(G) Representative live-cell images of HeLa  cells expressing GFP-PRC1-WT or -MEE and depleted for endogenous PRC1  using a PRC1  siRNA and a PRC1  sgRNA after doxycycline-induced Cas 9  expression. Microtubules  (SiR-Tubulin) and DNA  (SPY650) are shown in red. The cell membrane (CellMask) is highlighted in white and GFP-PRC1  is in green. Scalebar, 10 μm.",
    "ncbi_link": "GFP: 
Cas 9: 69900935
PRC1: 9055"
  },
  {
    "caption": "(J) Representative immunofluorescence  images of cells expressing GFP-PRC1-WT or -MEE after 72 hours siRNA depletion and doxycycline-induced knockout of endogenous PRC1. DNA, microtubules  and GFP-PRC1/GFP-PRC1-MEE are in blue, red and green respectively. Scalebar, 10μm.",
    "ncbi_link": "GFP: 
PRC1: 9055"
  },
  {
    "caption": "c, Log normalised expression of markers for epithelial (EPCAM), mature luminal epithelial (ESR1), myoepithelial (KRT5, KRT14 and ACTA2) and proliferating cancer cells (MKI67).",
    "ncbi_link": "ACTA2: 59
EPCAM: 4072
ESR1: 2099
KRT14: 3861
KRT5: 3852
MKI67: 4288"
  },
  {
    "caption": "e, Log normalised expression of markers for fibroblasts (PDGFRB, THY1, COL1A1, ITGB1 and S100A4), endothelial cells (PECAM1), T-cells (CD3D), CD8 T cells (CD8A), T-regulatory cells (FOXP3), B-cells (MS4A1), myeloid cells (CD68) and plasma cells (JCHAIN).",
    "ncbi_link": "CD3D: 915
CD68: 968
CD8A: 925
COL1A1: 1277
FOXP3: 50943
ITGB1: 3688
JCHAIN: 3512
MS4A1: 931
PDGFRB: 5159
PECAM1: 5175
S100A4: 6275
THY1: 7070"
  },
  {
    "caption": "b, Candidate transcriptional drivers of each CAF and PVL subset. Violin plots showing the log normalised gene expression (left) of the TF and its respective AUC regulon activity (right). TFs ZEB1 and FOXP1 enriched in myofibroblast-like CAFs, EGR2 and TCF7L2 enriched in inflammatory-like CAFs, MEF2C enriched in PVL cells and NR2F2 enriched in immature-PVL cells.",
    "ncbi_link": "EGR2: 1959
FOXP1: 27086
MEF2C: 4208
NR2F2: 7026
TCF7L2: 6934
ZEB1: 6935"
  },
  {
    "caption": "q-RT-PCR reveals that miR-181a/b silencing leads to upregulation of miR-181a/b predicted targets in SH-SY5Y cells. N=3 independent experiments.",
    "ncbi_link": "miR-181a: 406995"
  },
  {
    "caption": "miR-181-mimic transfection specifically inhibits Luciferase activity of constructs containing WT 3'-UTR predicted target sequences. Point mutations (mut) in miR-181a/b binding sites abolish Luciferase repression in all cases apart from PPARGC1A. Data are normalized to negative mimic transfection (dashed line). N=6 independent experiments.",
    "ncbi_link": "miR-181a: 406995
miR-181: 406955
PPARGC1A: 10891"
  },
  {
    "caption": "q-RT-PCR reveals upregulation of miR-181a/b targets in the eyes of miR-181a/b-1-/- vs. miR-181a/b-1+/+ animals. n≥5 animals/genotype.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "miR-181a/b-1-/- mice show increased mtDNA content vs. miR-181a/b-1+/+ mice as measured by q-PCR. N=4 animals/genotype.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "WB analysis (left panel) reveals increased levels of mitochondrial proteins in the eyes of miR-181a/b-1-/- (-/-) vs. miR-181a/b-1+/+ (+/+) mice (quantified in the right panel). Data are normalized to either p115 or Gapdh. N≥3 animals/genotype. Please note that all compared bands from +/+ and -/- samples are from the same blots which were cropped and shown split for the sake of data presentation clarity.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Cell death analysis shows that miR-181a/b silencing protects SH-SY5Y cells from FCCP treatment. N≥7 independent experiments.",
    "ncbi_link": "miR-181a: 406995"
  },
  {
    "caption": "TUNEL assays on eye and brain sections of stage (st)30 medakafish control and MO-injected embryos reveal a decrease in the number of apoptotic cells in both hccs-MO/miR-181a/b-MO- and cox7b-MO/miR-181a/b-MO-injected compared to hccs-MO- and cox7b-MO-injected embryos. Scale bars are 20μm.",
    "ncbi_link": "hccs: 101166931
cox7b: 101167565
miR-181a: 102466480"
  },
  {
    "caption": "Caspase assays show restored levels of caspase-3 and caspase-9 activities in hccs-MO/miR-181a/b-MO- and cox7b-MO/miR-181a/b-MO-injected embryos with respect to hccs-MO- and cox7b-MO-injected embryos. n≥5 embryos for each model.",
    "ncbi_link": "hccs: 101166931
cox7b: 101167565
miR-181a: 102466480"
  },
  {
    "caption": "Representative images of st30 medaka embryos injected with hccs-MO (B) alone or co-injected with miR-181a/b-MOs Co-injection of miR-181a/b-MOs rescues microphthalmia and microcephaly in both hccs-MO embryos. hccs-MO/miR-181a/b-MO- b-MO-injected embryos were treated with Baf-A1, PD98059 or HA14-1. Baf-A1 treatment counteracts the protective effect of miR-181a/b downregulation in hccs-MO/miR-181a/b-MO embryos PD98059 treatment does not interfere with the modulation of the MLS phenotype mediated by miR-181a/b downregulation HA14-1 treatment counteracts the effect of miR-181a/b downregulation in the hccs-MO/miR-181a/b-MO model Scale bars are 100μm.",
    "ncbi_link": "hccs: 101166931
miR-181a: 102466480"
  },
  {
    "caption": "Representative images of st30 medaka embryos injected with cox7b-MO (H) alone or co-injected with miR-181a/b-MOs Co-injection of miR-181a/b-MOs rescues microphthalmia and microcephaly in cox7b-MO embryos. cox7b-MO/miR-181a/b-MO-injected embryos were treated with Baf-A1, PD98059 or HA14-1. Baf-A1 treatment counteracts the protective effect of miR-181a/b downregulation in cox7b-MO/miR-181a/b-MO embryos PD98059 treatment does not interfere with the modulation of the MLS phenotype mediated by miR-181a/b downregulation Scale bars are 100μm.",
    "ncbi_link": "cox7b: 101167565
miR-181a: 102466480"
  },
  {
    "caption": "Percentage of embryos with or without MLS phenotype in the different conditions in hccs-MO embryos. N≥300 embryos/conditions.",
    "ncbi_link": "hccs: 101166931"
  },
  {
    "caption": "Percentage of embryos with or without MLS phenotype in the different conditions in cox7b-MO (N) embryos. N≥300 embryos/conditions.",
    "ncbi_link": "cox7b: 101167565"
  },
  {
    "caption": "Immunofluorescence analysis with anti-NeuN antibody in the retina of miR-181a/b-1+/+ and miR-181a/b-1-/- mice intravitreally injected with Rotenone or DMSO. RGCs are preserved in miR-181a/b-1-/- rotenone-injected mice with respect to controls at both one and two weeks after injection. Scale bars are 50μm.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "NADH dehydrogenase histochemical reaction on retinal sections of miR-181a/b-1+/+ and miR-181a/b-1-/- mice intravitreally injected with Rotenone or DMSO. At one week post-injection, NADH dehydrogenase activity is lost in RGCs (GCL, areas within dashed lines) of miR-181a/b-1+/+ Rotenone-injected eyes, while it is preserved in those of miR-181a/b-1-/- Rotenone-injected eyes. GCL, Ganglion Cells Layer ONL; INL, Inner Nuclear Layer; Outer Nuclear Layer. Scale bars are 50μm.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Immunofluorescence analysis, with an anti-CoxIV antibody, in the retina of miR-181a/b-1+/+ and miR-181a/b-1-/- mice, injected with either Rotenone or DMSO, showed preserved mitochondria in miR-181a/b-1-/- rotenone-injected eyes at one-week post-injection. Dashed boxes indicate the area of magnifications shown in right panels. Scale bars are 10μm.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Graphical representation of the results of the optokinetic tracking assays reported as fold change of cycles/degree. Visual acuity is preserved in miR-181a/b-1-/- rotenone-injected mice with respect to controls at both one and two weeks after injection. N=10.",
    "ncbi_link": "miR-181a: 735252"
  },
  {
    "caption": "Immunofluorescence analysis with anti-NeuN antibody in the retina of WT, Ndufs4-/-, Ndufs4-/-/miR-181a/b-1-/- and miR-181a/b-1-/- mice. RGCs are preserved in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/- mice. Scale bars are 50μm.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "Graphical representation of the results of the optokinetic tracking assays reported as fold change of cycles/degree. Visual acuity is preserved in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/- mice. N≥8.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "Electroretinographic analysis reveals amelioration of b-wave patterns in Ndufs4-/-/miR-181a/b-1-/- with respect to Ndufs4-/-mice. N≥5.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "Electron microscopy analysis shows amelioration of mitochondria morphology and increase of mitochondrial number in Ndufs4-/-/miR-181a/b-1-/- vs. Ndufs4-/- mice. Scale bars are 1μm. The quantitative increase of mitochondria is reported in C as number of mitochondria/RGC, at p30 and p55. N≥2 animals/genotype.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "Ndufs4-/-/miR-181a/b-1-/- mice show increased mtDNA content vs. Ndufs4-/- mice as measured by q-PCR. N≥4 animals/genotype.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "Biochemical activity of MRC complexes I, II and IV normalized by the percentage of citrate synthase (CS) activity in Ndufs4-/-/miR-181a/b-1-/- vs. Ndufs4-/- mice. N≥3 animals/genotype. p‐values were calculated by two tailed Student's t-test; Error bars are SEM.",
    "ncbi_link": "miR-181a: 735252
Ndufs4: 17993"
  },
  {
    "caption": "(A) Graph derived from two published data available in the PubMed GEO database (GSE6919 and GSE35988). The box charts depict the relative expression of ESM1 in benign, primary, and metastatic prostate cancer patients. The centre line donates the median value while the box contains the 25th to 75th percentiles of dataset. The whiskers mark the 5th and 95th percentiles, and values beyond these upper and lower bounds are considered outliers.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(B) Relative ESM1 mRNA expression and ESM1 protein expression in two sets of human metastatic PCa cell lines. P: parental cells, M: metastatic cells.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(C) Cell invasion assays of 22Rv1-M and PC3-M cells transfected with either Scramble-shRNA or ESM1-shRNA. The data are shown as the relative fold change of invasive cells compared with the shScramble group. Scale bar: 100 μm.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(D) Representative images of lungs, livers, intestines, and kidneys from mice 8 weeks after orthotopical injection of 22Rv1-M cells transfected with either Scramble-shRNA or ESM1-shRNA. Scale bar: 0.5 cm. Tumors were removed and weighed. Quantitative summary of tumor luminescence in different metastases measured in photons/second are shown.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(D) Elicitation of ESM1 overexpression using HA-tag antibody results in detectable ESM1 expression in the nucleus and cytoplasm of 22Rv1-P cells. Lamin A/C and α-tubulin were used as loading control in the nucleus and cytoplasm, respectively.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(F) Left, representative images of 22Rv1-P cells in the transwell invasion assay. Right, statistic data of invasive ability of ESM1 expressing cells. Scale bar: 100 μm.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(G) Left, representative bioluminescence images of lung metastasis in mice after tail vein injection of 22Rv1-Luc cells with different ESM1 expression patterns. Scale bar: 0.5 cm. Right, quantification of the lung bioluminescence by photons/ seconds.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(C) 22Rv1-P cells stably expressing ESM1 were treated with docetaxel at the indicated concentrations for 48 h. **",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(D) Cells with or without ESM1-NLS overexpression were subcutaneously injected (10, 100, 1000 cells per mouse) into NOD/SCID mice. Tumor formation ability and tumor weight were analyzed. Scale bar: 1 cm. Bars are the mean ± SD of indicated (n) independent experiments.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(E) Flow cytometry analysis of the ratio of CD44+ and CD133+ cells in the indicated cells with different subcellular localization types of ESM1 overexpression were performed.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(F) qRT-PCR analysis of the mRNA levels of the indicated genes in cells with different types of ESM1 overexpression. Differences in mRNA levels compared with vector cells are shown as fold changes presented as the mean ± SD of three independent experiments. *",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(E) The transcriptional activity of β-catenin in 22Rv1-P cells with different patterns of ESM1 overexpression. Bars are the mean ± SD of three independent experiments.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(F) Manipulating ESM1 expression impacts transcriptional activity of NFκB. Bars are the mean ± SD of three independent experiments.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(C) Immunoblotting analysis of 22Rv1-P cells with different ESM1 overexpression in the nucleus and cytoplasm were performed with the antibodies indicated.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(D) Suppression of β-catenin or NFκB in 22Rv1-P cells stably expressing ESM1-NLS were treated with docetaxel at the indicated concentrations for 48 h. ** P < 0.01 when compared to vector-shScramble cells by two-tailed Student's t test and error bars represent the standard deviation of three independent experiments.",
    "ncbi_link": "β-catenin: 1499
ESM1: 11082
NFκB: 4790"
  },
  {
    "caption": "(E) Tumor spheres formed by 22Rv1-P cells stably expressing ESM1-NLS with either β-catenin or NFκB shRNAs. Scale bar: 100 μm. Bars are the mean ± SD of three independent experiments. ## P< 0.01 when compared to vector-shScramble cells, ** P< 0.01 when compared to ESM1-NLS-shScramble cells by two-tailed Student's t test.",
    "ncbi_link": "β-catenin: 1499
ESM1: 11082
NFκB: 4790"
  },
  {
    "caption": "(F) Representative images and quantitative data comparing cell invasion of the indicated cells. Scale bar: 100 μm. Bars are the mean ± SD of three independent experiments. ## P< 0.01 when compared to vector-shScramble cells, ** P< 0.01 when compared to ESM1-NLS-shScramble cells by two-tailed Student's t test.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(A) Nuclear and cytosolic extracts of 22Rv1-M cells transfected with either shScramble or shCTNNB1 were prepared and the levels of indicated proteins were detected by immunoblotting.",
    "ncbi_link": "CTNNB1: 1499"
  },
  {
    "caption": "(E) HEK293T cells were co-transfected with the indicated β-catenin-Flag and ESM1-HA constructs. Cell extracts were immunoprecipitated with Flag-M2 agarose beads. Light chain was labeled as l.c.",
    "ncbi_link": "Flag: 
HA: 
β-catenin: 1499
ESM1: 11082"
  },
  {
    "caption": "(F) HEK293T cells were transfected with ESM1-HA constructs and pull-down was carried out with different purified GST-ARM fragments.",
    "ncbi_link": "GST: 
HA: 
ESM1: 11082"
  },
  {
    "caption": "(G) HEK293T cells were transfected with the indicated ESM1-GFP constructs. Cell extracts were pulled down with purified GST-ARM.",
    "ncbi_link": "GFP: 
GST: 
ESM1: 11082"
  },
  {
    "caption": "(B) HEK293T cells were transfected with the indicated ESM1 point mutant constructs. Cell extracts were pulled down with purified GST-ARM.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(C) Cell extracts of 22Rv1-M transfected with either Scramble-shRNA or ESM1-shRNA were immunoprecipitated with an β-catenin antibody and blotted with anti-TCF4 and anti-BCL9 antibody.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(E) Upper, Schematic diagram of ESM1-targeting short peptides. Lower, HEK293T cells were transfected with ESM1-HA constructs. Cell extracts were treated with the short peptides, pulled down with purified GST-ARM and blotted with anti-HA and anti-TCF4 antibody.",
    "ncbi_link": "HA: 
ESM1: 11082"
  },
  {
    "caption": "(F) HEK293T cells were transfected with the indicated ESM1 point mutant constructs. Cell extracts were pulled down with purified GST-ARM and blotted with an anti-TCF4 antibody.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "(G) ChIP-qPCR validation of β-catenin binding to the CCND1 and c-Myc promoter in 22Rv1-M cells transfected with either Scramble-shRNA or ESM1-shRNA. Bars are the mean ± SD of three independent experiments.",
    "ncbi_link": "CCND1: 595
ESM1: 11082
c-Myc: 4609"
  },
  {
    "caption": "(H) Upper, Schematic diagram of ChIP-qPCR primers targeting regions upstream of the CCND1 and c-Myc transcription start sites (TSSs). Bar graphs show β-catenin and ESM1 binding at the CCND1 and c-Myc promoter regions. Differences in DNA levels compared with IgG control are shown as fold changes presented as the mean ± SD of three independent experiments.",
    "ncbi_link": "CCND1: 595
c-Myc: 4609"
  },
  {
    "caption": "(J) The effects of ESM1 point mutants on tumor invasion and spheroid formation. Scale bar: 100 μm. Bars are the mean ± SD of three independent experiments.",
    "ncbi_link": "ESM1: 11082"
  },
  {
    "caption": "Western blot showing the protein level of CAMSAP2 in negative control and CAMSAP2 siRNA transfected hRPEs. GAPDH was used as loading control. Bar chart shows quantification of protein levels normalized to GAPDH in each condition.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Angular displacement and y FMI of negative control and CAMSAP2 siRNA transfected hRPEs moving on stiffness gradient gels.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Western blot showing the protein level of AKAP450 in negative control and AKAP450 siRNA transfected hRPEs. α-tubulin was used as loading control. Bar chart shows quantification of protein levels normalized to α-tubulin in each condition.",
    "ncbi_link": "AKAP450: 10142"
  },
  {
    "caption": "Angular displacement and y FMI of control and AKAP450 siRNA transfected hRPEs moving on stiffness gradient gels.",
    "ncbi_link": "AKAP450: 10142"
  },
  {
    "caption": "Left: Representative immunofluorescent staining of α-tubulin in control, CAMSAP2 siRNA transfected and centrinone-B (500 nM, 7 days) treated hRPEs. Scale bar: 20 μm. Right: Quantification of microtubule fluorescence intensity.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Western blot showing the protein level of α-tubulin in control, CAMSAP2 siRNA transfected and centrinone-B (500 nM, 7 days) treated hRPEs. GAPDH is used as loading control. Bar chart shows quantification of protein levels normalized to GAPDH in each condition.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Left: Representative live-cell fluorescence imaging of EGFP-EB1 in control, CAMSAP2 siRNA transfected and centrinone-B (500 nM, 7 days) treated hRPEs. Scale bar: 20 μm. Right: Quantification of EB1 growth speed obtained by plusTipTracker. Vinlin plot center lines denote the median, and dashed lines represent the 25th and 75th percentiles.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Western blot showing the protein level of active RhoA, total RhoA in negative control and CAMSAP2 siRNA transfected hRPEs. GAPDH is used as loading control. Bar chart shows quantification of protein levels normalized to GAPDH in each condition.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Left: Representative live-cell fluorescence imaging of GFP-AHPH in negative control and CAMSAP2 siRNA transfected hRPEs. Scale bar: 20 μm. Right: Quantification of GFP-AHPH fluorescence intensity.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Left: Representative immunofluorescent staining of pMLC (yellow) and DAPI (blue) in negative control and CAMSAP2 siRNA transfected hRPEs. Scale bar: 20 μm. Right: Quantification of pMLC fluorescence intensity. Below: Western blot showing the protein level of pMLC in negative control and CAMSAP2 siRNA transfected hRPEs. α-tubulin is used as loading control",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Left: Images showing collagen gel deformation at 0 h, 8 h and 24 h. HRPEs transfected with negative control, CAMSAP2 and AKAP450 siRNA were seeded in 1% collagen gel (yellow dashed lines). Scale bar: 5 mm. Right: Quantification of gel area.",
    "ncbi_link": "AKAP450: 10142
CAMSAP2: 23271"
  },
  {
    "caption": "Top: Representative live-cell fluorescence imaging of RFP-paxillin in negative control and CAMSAP2 siRNA transfected hRPEs. Time-lapse fluorescence imaging zoomed from the yellow box showed the assembly and disassembly stage of a single FA. Scale bar: 20 μm. Bottom: Quantification of FA area, assembly rate and disassembly rate obtained by FAAS. Vinlin plot center lines denote the median, and dashed lines represent the 25th and 75th percentiles.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Top: Schematic diagram of FA-MT contact analysis. Position of EB1 and paxillin were extracted from live-cell images, followed by automated co-localization identification. Scale bar: 20 μm. Bottom: Representative time-lapse fluorescence imaging of EGFP-EB1 and RFP-paxillin zoomed from the yellow box above showed the targeting of MT to FA. FA-MT contact ratio was calculated by the ratio of co-localization events to the total EB1 number.   FA-MT contact ratio of negative control, CAMSAP2, AKAP450 siRNA transfected and centrinone-B (500 nM, 7 days) treated hRPEs. Vinlin plot center lines denote the median, and dashed lines represent the 25th and 75th percentiles.   ",
    "ncbi_link": "AKAP450: 10142
CAMSAP2: 23271"
  },
  {
    "caption": "Western blot showing the protein level of ELKS in negative control and ELKS siRNA transfected hRPEs. α-tubulin was used as loading control. Bar chart shows quantification of protein levels normalized to α-tubulin in each condition.",
    "ncbi_link": "ELKS: 23085"
  },
  {
    "caption": "FA-MT contact ratio of negative control and ELKS siRNA transfected hRPEs. Vinlin plot center lines denote the median, and dashed lines represent the 25th and 75th percentiles.",
    "ncbi_link": "ELKS: 23085"
  },
  {
    "caption": "Y FMI of negative control and ELKS siRNA transfected hRPEs moving on stiffness gradient gels.",
    "ncbi_link": "ELKS: 23085"
  },
  {
    "caption": "Left: Representative immunofluorescent staining of GM130 (yellow), F-actin (gray) and DAPI (blue) in negative control and CAMSAP2 siRNA transfected hRPEs at the edge of the wound after 8 h. Scale bar: 50 μm. Middle: Schematic diagram of Golgi-nucleus orientation towards the front (45°-135°) or the rear (-45°- -135°). Right: Quantification of the percentage of Golgi-nucleus orientation towards the front or rear of the cell.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Left: Representative immunofluorescent staining of GM130 (yellow) and DAPI (blue) in negative control and CAMSAP2 siRNA transfected hRPEs on the stiffness gradient gel. Scale bar: 20 μm. Middle: Schematic diagram of Golgi-nucleus orientation towards the stiff side (45°-135°) or the soft side (-45°- -135°). Right: Quantification of the percentage of Golgi-nucleus orientation towards the stiff or soft side.",
    "ncbi_link": "CAMSAP2: 23271"
  },
  {
    "caption": "Naïve CD4+ T cells were isolated from the spleen and LNs of WT, Stim2fl/fl Cd4Cre (S2), Orai1fl/fl Cd4Cre (O1) and Stim1fl/fl Cd4Cre (S1) mice and differentiated into Th1, Th17 and iTreg cells. (A) Fura-2 loaded cells were stimulated with 0.3 μM ionomycin to induce SOCE. Representative Ca2+ traces (left) and peak Ca2+ levels (right). Data are from the mean ± SEM of 4 mice per group.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Orai1: 109305
Stim1: 20866
Stim2: 116873"
  },
  {
    "caption": "(B) Induction of colitis in Rag1-/- mice by adoptive transfer of naive CD4+ T cells from wildtype, Stim2fl/fl Cd4Cre, Orai1fl/fl Cd4Cre and Stim1fl/fl Cd4Cre mice. Weight curves of recipient Rag1-/- mice following injection of naive CD4+ T cells. Data are from two independent experiments with 8 recipient mice per group.",
    "ncbi_link": "Cd4: 12504
Cre: 2777477
Orai1: 109305
Rag1: 19373
Stim1: 20866
Stim2: 116873"
  },
  {
    "caption": "(C) H&E stains of colon tissues and histological inflammation scores of Rag1-/- mice 8 weeks after T cell transfer. Data are from one representative experiment with 5 mice per group.",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "(D-E) Representative flow cytometry plots and frequencies of donor CD4+ T cells producing IFNγ, IL-17A, TNF or expressing Foxp3 that were isolated from the mesenteric LNs of recipient Rag1-/- mice. Data are from 2 independent experiments with 3-8 mice per group.",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "(F) Relative mRNA expression of markers for enterocytes (ALPI), goblet cells (MUC2), and entero-endocrine cells (CHGA) was quantified by RT-PCR in differentiated human colon monolayers after addition of 1 µM BTP2.",
    "ncbi_link": "ALPI: 248
CHGA: 1113
MUC2: 4583"
  },
  {
    "caption": "(A-C) Acute administration of the CRAC channel blocker CM4620 inhibits CRAC currents (Icrac). (A) Time course of peak amplitudes of ICRAC before and after application of 3 μM CM4620 to HEK293 cells transfected with ORAI1 and STIM1. (B) Current-voltage (I-V) relationship of ICRAC before and after CM4620 treatment. I-Vs were obtained at the time points indicated by the arrowheads in (A). (C) Fractional blockade of ICRAC by CM4620 was measured by comparing current amplitudes before and after CM4620 administration (arrowheads) using the formula 1- (ICM4620 / ICtrl). Data are from 8 cells per conditions and shown as the mean ± SEM.",
    "ncbi_link": "ORAI1: 84876
STIM1: 6786"
  },
  {
    "caption": "(G) Representative H&E staining of the distal colon of Rag1-/- mice treated with vehicle or CM4620. Colitis scores of 9 mice per cohort. Each symbol represents one mouse.",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "A, B BMDCs were treated with OxPAPC or DPPC (40 μg/ml) for 60 min followed by R837 stimulation (5 μg/ml). (B) mRNA was harvested after 2 h, and expression of IL-6 and IL-12 was measured by real-time PCR and normalized to G6pdx. Unpaired two-tailed t-test. Data (mean ± SD) are representative of three independent experiments.",
    "ncbi_link": "G6pdx: 
IL-12: 16160///16159
IL-6: 16193"
  },
  {
    "caption": "A IL-12 production of BMDC from wild-type, Nrf2−/−, Pparg−/−, and Pparg litter mate control mice normalized to medium control (open bars). Cells were treated with the indicated lipids (filled bars) for 60 min prior TLR 7 ligation with R837 (5 μg/ml) for 18 h. Lipids were used at starting concentrations of 40 μM (POVPC, PGPC, and KOdiAPC), 40 μg/ml (OxPAPC), 20 μM (15d-PGJ2), and 1.25 μM (EC), depicted as black bars, and 2-fold serial dilutions thereof (gray bars). Data represent mean ± SEM of triplicates from one of three independent experiments.",
    "ncbi_link": "Nrf2: 18024
Pparg: 19016"
  },
  {
    "caption": "B Expression of Nrf2 target genes Hmox1 and Nqo1 in wild-type and Nrf2−/−BMDM stimulated with EC (2 μM) for 60 min. Gene expression levels are presented relative to that of untreated cells after normalization to G6pdx. Data (mean ± SEM) are representative of two independent experiments.",
    "ncbi_link": "G6pdx: 
Hmox1: 15368
Nrf2: 18024
Nqo1: 18104"
  },
  {
    "caption": "C, D mRNA expression levels of the Nrf2 targets Gclc and Gsta3 (C) and of the pro-inflammatory cytokines IL-6 and IL-12 (D) in wild-type, PPAR-γ-deficient, and Nrf2-deficient BMDM after treatment with EC or 15d-PGJ2 for 60 min followed by LPS treatment for 3 h. Expression levels are normalized to G6pdx. Data represent mean ± SEM of triplicate cultures from one of two independent experiments.",
    "ncbi_link": "G6pdx: 
Gclc: 14629
Gsta3: 14859
IL-12: 16160///16159
IL-6: 16193
Nrf2: 18024
PPAR-γ: 19016"
  },
  {
    "caption": "E mRNA expression of the indicated chemokines as determined by qPCR. Wild-type BMDCs were treated with EC (1 μM) or 15d-PGJ2 (20 μM) for 60 min followed by R837 stimulation (5 μg/ml) for 3 h. Expression levels are shown normalized to G6pdx. Data (mean ± SEM, n = 2) are representative of three independent experiments.",
    "ncbi_link": "G6pdx: "
  },
  {
    "caption": "mRNA expression of the Nrf2 targets Hmox1 and Nqo1 normalized to G6pdx expression. BMDCs were treated for 60 min with 500 nM cEC or DPPC followed by R837 stimulation (5 μg/ml) for 3 h. Data (mean ± SD) are representative of three independent experiments. *P < 0.05; **P < 0.01; unpaired two-tailed t-test.",
    "ncbi_link": "G6pdx: 
Hmox1: 15368
Nrf2: 18024
Nqo1: 18104"
  },
  {
    "caption": "mRNA quantification of the indicated chemokines relative to G6pdx expression. BMDC were pretreated for 60 min with 500 nM cEC or the variant BisRed prior to R837 stimulation (5 μg/ml) for 3 h. Data (mean ± SD) are representative of three independent experiments. *P < 0.05; **P < 0.01; unpaired two-tailed t-test.",
    "ncbi_link": "G6pdx: "
  },
  {
    "caption": "Representative immunofluorescence of primary cilium in WT or Mecp2 null MEF cells. Cells were starved for 48 h before staining with anti-γ-tubulin (green) and anti-acetylated α-tubulin (red) antibodies. Merge of all channels and DAPI staining (blue) is depicted for both genotypes. Scale bar 20 µm, and 10 µm in the enlarged image. Arrows indicate not ciliated cells.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Cilia were counted and analysed with ImageJ to quantify the percentage of ciliated cells (n=134 WT and n=140 Mecp2 null cells) (B) and the cilium length (n=104 WT and n=43 Mecp2 null cells) (C). The graphs show the average of three independent experiments (mean ± S.E., **p<0.01, by Mann-Whitney test; ***p<0.001, by Student's t-test).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Representative immunofluorescence of primary cilium in hTERT-RPE-1 cells silenced with MECP2- or control-siRNAs. Cells were starved for 48 h before staining with anti-γ-tubulin (green) and anti-acetylated α-tubulin (red) antibodies. Scale bar 10 µm, and 5 µm in the enlarged image. Arrows indicate not ciliated cells.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "Cilia were counted and analysed with ImageJ to quantify the percentage of ciliated cells (n=191 CTRL and n=197 siMeCP2 cells) (G) and the cilium length (n=50 CTRL and n=50 siMeCP2 cells) (H). The graphs show the mean ± S.E of three independent experiments (***p<0.001, by Mann-Whitney test (G) or Student's t-test (H)).",
    "ncbi_link": "MeCP2: 4204"
  },
  {
    "caption": "Representative immunofluorescence of primary cilium in WT and Mecp2 null primary cortical neurons at DIV7 and DIV14. Scale bar 10 µm, and 5 µm in the enlarged image. Arrows indicate not ciliated cells.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Percentage of ciliated cells (M) and cilium length (N) were analysed (n=26 WT and n=34 Mecp2 null astrocytes). Histograms represent the average of three independent experiments (mean ± S.E., *p<0.05, Student's t test).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Representative immunofluorescence of Mecp2 null cortical neurons infected at DIV0 with lentiviruses expressing GFP or MeCP2iresGFP. Neurons were fixed at DIV7 and immunostained with anti-AC3 antibody to detect the primary cilium. GFP-positive cells represent infected cells. Scale bar 20 µm, and 10 µm in the enlarged image.",
    "ncbi_link": "GFP: 
Mecp2: 4204
MeCP2: 4204"
  },
  {
    "caption": "Western blot comparing MeCP2 levels in Mecp2 null neurons infected with lentiviruses expressing GFP or MeCP2iresGFP with respect to WT neurons. Data are normalized to total protein content, visualized by a TGX stain-free technology.",
    "ncbi_link": "GFP: 
Mecp2: 4204
MeCP2: 4204"
  },
  {
    "caption": "MECP2 expression in null neurons induced a significant recovery of ciliogenesis. (C) The graph represents the percentage of ciliated cells, counting n=50 WT and n=100 null cells of two different preparations (mean ± S.E., ***p<0.001, by two-way ANOVA followed by Bonferroni post-hoc test). Statistical analysis reported a significant interaction (F (1,135) = 8.264), a significant genotype effect (F (1,135) = 37.59) and a significant infection effect (F (1,135) = 26.89). (D) The graph represents the mean ± S.E. of cilium length in WT and Mecp2 null neurons infected with GFP or MeCP2iresGFP expressing lentiviruses, counting n=28 cells of two different preparations (**p<0.01, ***p<0.001, by two-way ANOVA followed by Bonferroni post-hoc test). Two-way ANOVA reported a significant interaction (F (1,103) = 6.405), a significant genotype effect (F (1,103) = 35) and a significant infection effect (F (1.103) = 4.039).",
    "ncbi_link": "GFP: 
Mecp2: 4204
MECP2: 4204
MeCP2: 4204"
  },
  {
    "caption": "MECP2-silenced or control hTERT-RPE-1 cells were starved for 48 h before treatment with 200 nM and 500 nM SAG for 24 h. Cells were stained with anti-Smo and anti-acetylated α-tubulin antibodies. The percentages of Smo-positive cilia were calculated. The graph shows the average of three independent experiments (mean ± S.E., *** p<0.001, by two-way ANOVA followed by Bonferroni post hoc test). Two-way ANOVA demonstrated a significant silencing effect (F (1, 12) = 160; p<0.0001), a significant SAG treatment (F (2, 12) = 259.4; p<0.0001) and a significant interaction (F (2, 12) = 36.85; p<0.0001).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "WT or Mecp2 null MEF cells were treated with SAG (200 and 500 nM) for 24 h and the percentages of Smo-positive cilia were calculated. The graph shows the average of three independent experiments (mean ± S.E., *p<0.05, by two-way ANOVA followed by Bonferroni post hoc test). Two-way ANOVA indicated a significant genotype effect (F (1, 12) = 11.22; p<0.01) and a significant SAG treatment (F (2, 12) = 11.7; p<0.0001).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Gli1 protein levels were measured by Western blot in untreated (UT) and 100 nM SAG-treated WT and Mecp2 null MEF cells (n=5/6). Representative bands of Gli1, Mecp2 and α-tubulin are depicted above the histogram, which shows the mean ± S.E of the percentage of Gli1 expression levels, compared to the untreated WT samples (**p<0.01, ***p<0.001, by two-way ANOVA, followed by Bonferroni post hoc test). Two-way ANOVA reported a significant interaction (F (1, 18) = 6.652; p<0.05), a significant genotype effect (F (1,18) = 15.95; p<0.001) and a significant treatment (F (1, 18) = 20.15; p<0.001).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Gli1 protein levels were measured by Western blot in WT and Mecp2 null neurons, following SAG treatment (200 and 400 nM). Representative bands of Gli1, Mecp2 and α-tubulin are depicted above the histogram, which shows the mean ± S.E of the percentage of Gli1 expression levels, compared to the untreated WT samples (*p<0.05, ***p<0.001, by two-way ANOVA, followed by Bonferroni post hoc test). Two-way ANOVA indicated a significant interaction (F (2, 20) = 3.788; p<0.05), a significant genotype effect (F (1, 20) = 4.362; p<0.05) and a significant treatment (F (2, 20) = 13.5; p<0.001).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Gli1 mRNA expression levels upon SAG exposure in MEF cells (n=7 WT and n=9 null samples) (F; SAG 100 nM) and cortical neurons (n= 15 WT and n=12 null samples) (G; SAG 400 nM). The graphs show the mean ± S.E. of the fold change derived from at least three independent experiments (mean ± S.E., **p<0.01, by two-way ANOVA, followed by Bonferroni post hoc test).",
    "ncbi_link": "Gli1: 14632"
  },
  {
    "caption": "Primary cilium length was measured in the cortex of Mecp2 null mice Average cilium length was measured in the cortex (mean ± S.E., n=4 WT and n=3 Mecp2 null) (B; *p<0.05, by Mann-Whitney test) and for each cortical layer (C; ***p<0.001, **p<0.01, *p<0.05, by two-way ANOVA followed by Bonferroni post hoc test). In C, cilium length is analysed in separate cortical layers while in B, the values indicate the average of cilium lengths for each layer.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Representative immunostaining of Arl13b (green) in the internal (IGL) and external (EGL) granular layers of Mecp2 null (n=3) and heterozygous (het) cerebella (n=3) at P7, and the corresponding WT (n=3 males and n=3 females). Nuclei were stained with DAPI (blue). Scale bar 5 µm.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Primary cilium length was measured in the cerebellum of Mecp2 null and heterozygous mice. Histograms show the mean ± S.E. of cilium length (n=3 males WT, n=3 females WT, n=3 Mecp2 null and Mecp2 het; **p<0.01, ***p<0.001, by Mann-Whitney test) in Mecp2 null (E) and heterozygous (F) mice, compared to the corresponding WT.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Gli1 protein levels were measured by Western blot in WT and Mecp2 null cerebellum (n=7 WT and n=6 Mecp2 null). Representative bands of Gli1 and α-tubulin are depicted beside the histogram, which shows the mean ± S.E of the percentage of Gli1 expression levels, compared to WT animals (*p<0.05, by Student's t test).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "The mRNA expression levels of Gli1 and its downstream genes (Cyclin D1 and D2) were analyzed in WT and Mecp2 null cerebella (n=8 WT and n=7 Mecp2 null). The graph shows the fold change of transcripts compared to WT (mean ± S.E., *p<0.05, by Student's t test).",
    "ncbi_link": "Cyclin D1: 12443
D2: 12444
Gli1: 14632
Mecp2: 17257"
  },
  {
    "caption": "WT and Mecp2 null MEF cells were starved for 48 h and then treated with the HDAC6 inhibitor tubacin (TUB) (1 μM) for 48 h or with DMSO (VEH) or left untreated (UT). Cells were fixed, stained for anti-acetylated α-tubulin and cilia were counted. The graph shows the percentage of ciliated cells out of three independent experiments (mean ± S.E., *p<0.05, **p<0.01, by two-way ANOVA followed by Bonferroni post hoc test). Two-way ANOVA reported a significant genotype effect (F(1, 10) = 17.94; p<0.01), a significant tubacin treatment (F(2, 10) = 4.425; p<0.05) and a significant interaction (F(2, 10) = 7.266; p<0.05).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "MECP2 silenced or control hTERT-RPE-1 cells were starved for 48 h, treated with tubacin (TUB, 1 µM) for 24 h and then exposed to 200 nM SAG for 24 h in the presence of tubacin. Cells were stained with anti-Smo and anti-acetylated α-tubulin antibodies and the percentages of Smo-positive cilia were calculated. The graph shows the averages of three independent experiments (mean ± S.E., **p<0.01, by three-way ANOVA followed by Tukey's post hoc test). Statistical analysis reported a significant difference between genotype (F (1, 2) = 21.47; p<0.001), a significant SAG effect (F (2, 2) = 154.5; p<0.0001) and a significant tubacin effect (F (1, 2) = 25.18; p<0.001). In details, a significant interaction between genotype and SAG treatment (F (2, 2) = 5.413; p<0.05) and between SAG and tubacin treatment (F (2, 2) = 6.939; p<0.01) were reported, demonstrating respectively a difference between CTRL and MeCP2 depleted cells in response to SAG and a different SAG effect when cells were treated with tubacin.",
    "ncbi_link": "MECP2: 4204
MeCP2: 4204"
  },
  {
    "caption": "Representative immunostaining of Smo (green) and acetylated α-tubulin (red) in control (CTRL) and silenced (siMeCP2) hTERT-RPE-1 cells, after stimulation with 200 nM SAG in the presence or absence of the HDAC6 inhibitor tubacin (TUB). Scale bar 50 µm, and 20 µm in the enlarged image.",
    "ncbi_link": "MeCP2: 4204"
  },
  {
    "caption": "Representative images of MAP2 positive WT and Mecp2 null neurons (DIV7). At DIV5 neurons were treated with tubacin (TUB, 1µM for 48 h), Aurora A inhibitor TC-S 7010 (TC-S, 7 nM for 48 h) or left untreated and morphologically analyzed by Sholl analysis plug-in. Scale bar 20 µm. The graph reports the mean ± S.E. of the number of intersections measured 85 to 145 nm from the soma calculated by Sholl analysis for WT (n=39 neurons) and Mecp2 null neurons, when left untreated (n=57 neurons) or treated with tubacin (n=53 neurons) or TC-S 7010 (n=38 neurons). Data from WT and null neurons were compared by Mann-Whitney test (**p<0.01); drug effects on null cells were analyzed by one-way ANOVA followed by Dunn's post hoc test (*p<0.05, **p<0.01).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "Representative images of WT and Mecp2 null neurons (DIV14) immunostained for MAP2 (white), Synapsin1/2 (green) and Shank2 (red). Mecp2 null cells were treated at DIV12 with tubacin (TUB, 1µM for 48 h) or Aurora A inhibitor TC-S 7010 (TC-S, 7 nM for 48 h). Scale bar 15 µm, and 5 µm in the enlarged image.",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "The graphs represent the mean ± S.E. of the Synapsin1/2 and the Shank2 puncta density in WT (n=67 neurons) and Mecp2 null neurons, when untreated (n=51 neurons) or treated with tubacin (n=59 neurons) or TC-S 7010 (n=55 neurons). Neurons derived from at least 6 different biological replicates. Data from WT and null neurons were compared by Mann-Whitney test (**p<0.01, ***p<0.001); drug effects on null cells were analyzed by one-way ANOVA followed by Dunn's post hoc test (*p<0.05, ***p<0.00­­1). The graph depicts the mean ± S.E. of the number of co-localized pre- and post-synaptic puncta (n=20 neurons deriving from 3 different biological samples). Data from WT and null neurons were compared by Mann-Whitney test (***p<0.001); drug effects on null cells were analyzed by one-way ANOVA followed by Dunn's post hoc test (*p<0.05).",
    "ncbi_link": "Mecp2: 17257"
  },
  {
    "caption": "D  ChIP-seq  signal for FLAG-PDS5A  and FLAG-PDSB  (ChIP  assays were performed with antibodies against Flag  and PDS5A/B) centered at TSS of promoters (± 3 kb) across all peaks called for each of the proteins in DMSO  treated PDS5A-dTAG  or PDS5B-dTAG  cells, showing the drastic reduction in PDS5A/B enrichment on chromatin  after degradation. Top: normalized signal intensities for each protein.",
    "ncbi_link": "PDS5A: 23244
PDS5B: 23047"
  },
  {
    "caption": "F ChIP-qPCR  using Flag  antibody demonstrating complete depletion of PDS5A  or PDS5B  (left, right) in H19/IGF2 imprinting locus and the promoter region of PCDH10, NC represents a negative binding site. Data are represented as mean±SD from three biological replicates.",
    "ncbi_link": "H19/IGF2: 105259599
PCDH10: 57575"
  },
  {
    "caption": "(a) Atg7−/− livers display decreased ERK phosphorylation. Immunoblots for the indicated proteins in liver homogenate (Hom) and cytosolic (Cyt) fractions of control (Con) and liver-specific Atg7−/− mice are shown. The bars represent mean±s.e.m. *P0.05, **P0.01, ***P0.001 compared with Con; Student's t-test, n=4.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(b) Atg7−/− livers display decreased ERK2 dimers. Immunoblots show the indicated proteins in Hom from Con and Atg7−/− livers. The bars represent mean±s.e.m. *P0.05, ***P0.001 compared to Con; Student's t-test, n=4-5. Arrows indicate p42 monomers and dimers.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(c) Atg7−/− brown adipose tissues (BAT) display decreased ERK phosphorylation. Immunoblots for indicated proteins in Hom from Con and Atg7−/−BAT. The bars represent mean±s.e.m. **P0.01 compared with Con; Student's t-test, n=4-6.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(d) Atg7−/− livers exhibit decreased nuclear ERK phosphorylation. Immunoblots show the indicated proteins in homogenate (Hom, lane 1) and nuclear fractions (lanes 2-5) from Con and Atg7−/− livers. The bars represent mean±s.e.m. ***P0.001 compared with Con; Student's t-test, n=4-5.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(e) LC3 C terminus glycine-deleted (ΔG) mutants exhibit decreased ERK phosphorylation. Immunoblots for indicated proteins in total lysates from CFP-LC3- and CFP-LC3ΔG-transfected NIH/3T3 cells exposed or not to EGF (10 min). The bars represent mean±s.e.m. ***P0.001 compared with Con; Student's t-test, n=8.",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "(a) Atg5−/− MEFs display reduced ERK phosphorylation during nutrient deprivation. Quantification of P-ERK levels normalized to total ERK (detected by immunoblotting) in WT and Atg5−/− MEFs cultured in the absence of serum for indicated times. The bars represent mean±s.e.m. *P0.05 compared with corresponding WT value; ***P0.001, ****P0.0001 compared with 10 min serum-starved Atg5−/− MEFs; ANOVA-Bonferroni post hoc test, n=3.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(b) Serum-deprived Atg5−/− MEFs display decreased ERK and p90RSK phosphorylation. Immunoblots for the indicated proteins in total lysates from 2 h serum-deprived WT and Atg5−/− MEFs. The bars represent mean±s.e.m. *P0.05, ***P0.001 compared with Con; Student's t-test, n=3.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c) Atg5−/− MEFs display decreased nuclear ERK activity. Immunoblots for phosphorylated HA (haemagglutinin)-tagged Elk1 in total lysates from 2 h serum-deprived WT and Atg5−/− MEFs cells exposed or not to EGF (10 min).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(d) Atg5−/− MEFs display decreased Elk1-driven gene expression. Elk1-driven ZFP36 mRNA levels from 2 hserum-deprived WT and Atg5−/− MEFs cells exposed or not to EGF (10 min). The bars represent mean±s.e.m. ***P0.001 compared with Con; Student's t-test, n=3. (",
    "ncbi_link": "Atg5: 11793
Elk1: 13712
ZFP36: 22695"
  },
  {
    "caption": "(e) Decreased ERK phosphorylation in Atg5−/− MEFs occurs independently of changes in ERK phosphatases. Immunoblots for the indicated proteins in 2 h serum-deprived WT MEFs transfected with scrambled siRNA (scr), and Atg5−/− MEFs transfected with scr or siRNAs against MKP3 or PP2A in the presence or absence of EGF. The bars represent mean±s.e.m., n=3.",
    "ncbi_link": "Atg5: 11793
MKP3: 67603
PP2A: 51792///19052"
  },
  {
    "caption": "(a) Mutations in FRS on ERK2 decrease colocalization of ERK2 with ATG5-ATG12, LC3 and WIPI1. Immunofluorescence (IF) showing colocalization (depicted as white pixels by 'colocalization finder application') of WT-ERK2-HA, FRS ERK2 mutants (L198A-, L232A-, L198A/L232A-, Y261A-ERK2-HA) or common docking (CD) mutant (D319N-ERK2-HA) with ATG5-ATG12 (panels 1-6), LC3 (panels 7-12) or WIPI1 (panels 13-18) in EGF-treated NIH/3T3 cells. ERK2 is stained in red, and autophagy proteins are stained in green. Scale bar, 10 μm. The bars represent mean±s.e.m. **P0.01, ****P0.0001 compared with WT-ERK2-transfected cells; Student's t-test, 50 cells analysed from n=2. (",
    "ncbi_link": "ERK2: 26413"
  },
  {
    "caption": "(b) Mutations in FRS on ERK2 decrease colocalization of ERK2 with nuclearATG5-ATG12 or LC3. IF showing colocalization (white pixels) of WT-ERK2-HA (red), FRS ERK2 mutants (L198A-, L232A-, L198A/L232A-, Y261A-ERK2-HA) or common docking (CD) mutant (D319N-ERK2-HA) with ATG5-ATG12 (panels 1-6) or LC3-II (panels 7-12) in EGF-treated NIH/3T3 cells. Scale bar, 5 μm. The bars represent mean±s.e.m. **P0.01, ***P0.001, ****P0.0001 compared with WT-ERK2-transfected cells; Student's t-test, 50 cells analysed from n=2. Arrows depict colocalization.",
    "ncbi_link": "ATG5: 11793
ERK2: 26413"
  },
  {
    "caption": "(c) ATG5-ATG12 conjugation is required for ERK phosphorylation. Immunoblots for P-ERK, total ERK and β-actin in NIH/3T3 cells transfected with WT ATG5 or the conjugation-defective ATG5 K130R mutant and treated with EGF (10 min). The bars represent mean±s.e.m. *P0.05 compared with WT ATG5-transfected cells; Student's t-test, n=3.",
    "ncbi_link": "ATG5: 11793"
  },
  {
    "caption": "a) ATG4B depletion increases steady-state LC3-II levels. Immunoblots for indicated proteins in NIH/3T3 cells transfected with scrambled siRNAs (scr) or siRNAs against ATG4B (siATG4B) in presence/absence of EGF. Bars represent mean±s.e.m. *P0.05, ***P0.001 compared with scr; Student's t-test, n=4.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(b) siATG4B cells exhibit increased autophagic vesicles. Representative electron micrographs depicting autophagic vesicles (indicated by black arrows) in scr and siATG4B NIH/3T3 cells.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(c) ATG4B depletion does not increase autophagic flux in serum-fed cells. Immunoblots for indicated proteins in lysates from scr or siATG4B NIH/3T3 cells in presence/absence of lysosomal inhibitors, ammonium chloride and leupeptin (Inh) for 2 h. Scale bars, 1 μm. Bars represent mean±s.e.m., n=3.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(d) siATG4B cells display increased nuclear LC3-II. Images for LC3-II (red) in scr or siATG4B NIH/3T3 cells in presence/absence of EGF (10 min). Scale bar, 5 μm. Bars represent mean±s.e.m. ***P0.001 compared with scr; Student's t-test, 60 cells from n=2.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(e) ATG4B deficiency increases P-ERK/LC3-II colocalization. Immunofluorescence (IF) for P-ERK (green)/LC3 (red) colocalization in scr or siATG4B NIH/3T3 cells in presence/absence of EGF (10 min). Scale bars, 10 μm. Bars represent mean±s.e.m. **P0.01, ***P0.001 compared with scr; Student's t-test, 60 cells from n=2.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(f) ATG4B-deficient cells display increased nuclear P-ERK/LC3 colocalization. IF depicting P-ERK (green)/LC3 (red) colocalization in nuclei of scr or siATG4B NIH/3T3 cells in presence/absence of EGF. Scale bars, 5 μm. Bars represent mean±s.e.m. **P0.01, ***P0.001 compared with scr; Student's t-test, 60 cells from n=2.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "(g) ATG4B deficiency augments EGF-induced MEK and ERK phosphorylation. Immunoblots for P- and total MEK and ERK, LC3 and GAPDH in total lysates from scr or siATG4B NIH/3T3 cells in presence/absence of EGF. Bars represent mean±s.e.m., n=3.",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "h) ATG4B deficiency increases nuclear P-ERK levels. Native (top)/inverted images (bottom) showing nuclear P-ERK content. P-ERK fluorescence in untreated (Con)/EGF-treated scr or siATG4B NIH/3T3 cells is shown. Scale bars, 5 μm. Bars represent mean±s.e.m. **P0.01, ***P0.001 compared with scr; Student's t-test, 60 cells from n=2. Nuclei are blue (DAPI).",
    "ncbi_link": "ATG4B: 66615"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). A: Spinning disc confocal live cell imaging of Alexa 555-EGF (555-EGF) shown as vesicle tracking with time represented as a colour spectrum. Tracking started 5 min after addition of 20 ng/mL 555-EGF for the indicated durations. Scale bar: 10 μm. ",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). B: Immunofluorescence staining of EGFR following 5 or 15 min stimulation with 20 ng/mL EGF. Scale bar: 20 μm.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). C: Quantification of EGFR vesicles in a perinuclear region (within 30 μm diameter of the centre of the nucleus) Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). D: Cells were stimulated with 20 ng/mL 555-EGF for 15 or 30 min before immunofluorescence staining against EGFR. Scale bar: 10 μm.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). E: Quantification of percentage of total EGFR vesicles that colocalise with 555-EGF Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). F: Cells stably expressing mCherry-Rab5 were stimulated with 20 ng/mL EGF for indicated times before immunofluorescence staining against EGFR. Scale bar: 10 μm.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). G: Pearson's colocalisation coefficient between mCherry-Rab5 and EGFR Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. A: Control, sgAtg7, or sgAtg16l1 cells were treated with 2 ng/mL EGF for 15 min. Cells were then processed for staining using anti-EEA1 antibodies and PI(3)P probe (Alexa 488-labelled 2XFYVE domains). To ensure the specificity of the probe, control cells were pre-treated with 5 mM 3'MA for 30 min. Scale bar: 10 μm. B: Quantification of PI(3)P+ label intensity per cell (in A). C: Pearson's colocalisation coefficient between PI(3)P and EEA1 (in A). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg16l1: 77040
Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. D: Control and sgAtg7 cells were stimulated 20 ng/mL EGF for 5 or 15 min before immunofluorescence staining against EEA1 and EGFR. Scale bar: 10 μm. E: Pearson's colocalisation coefficient between EEA1 and EGFR (in D). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. F: Endogenous VPS34 was immunoprecipitated from control and sgAtg7 cells that were treated with 2 ng/mL EGF for 15 min then lysed in CHAPS-containing detergent buffer and binding partners detected by western blotting. G: Densitometry analyses of proteins coimmunoprecipitated with endogenous VPS34 (in F). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). A: Cells transiently expressing YFP-Galectins (YFP-Gal3, -Gal8, or -Gal9) were stimulated with 2 ng/mL EGF for 15 min before fixation and immunofluorescence staining against EEA1. Scale bar: 10 μm. B: Quantification of percentage of total EEA1 vesicles that colocalise with YFP-Galectins (in A).Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Gal3: 
Gal8: 
Gal9: 
YFP: 
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). C: Cells transiently expressing YFP-Gal8 were stimulated with 20 ng/mL Alexa 555-EGF (555-EGF) for 15 min. Scale bar: 10 μm. D: Quantification of the percentage of YFP-Gal8-labelled vesicles that colocalise with 555-EGF in control or ATG7-deficient cells (in C). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Gal8: 
YFP: 
Atg7: 74244
ATG7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). E: Cells transiently expressing YFP-Gal8 were treated 100 μM monensin for 1 hr and stimulated with 2 ng/mL EGF for 15 min before fixation and immunofluorescence staining against EEA1. Scale bar: 10 μm. F: Quantification of percentage of total EEA1 vesicles that colocalise with YFP-Gal8 upon monensin treatment (in E). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, ** p<0.01, *** p<0.001. ",
    "ncbi_link": "Gal8: 
YFP: 
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). A: Cells stably expressing GFP-LC3 were treated with 100 μM monensin in the presence or absence of bafilomycin A1 (20 nM) for 1 hr and stimulated with 2 ng/mL EGF for 15 min before fixation and immunofluorescence staining against EEA1. White arrows indicate colocalisation. Scale bar: 10 μm. B: Quantification of percentage of total EEA1 vesicles that colocalise with GFP-LC3 (in A). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "GFP: 
Atg7: 74244
LC3: 81631
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). C: Cells were treated for 1 hr with 100 μM monensin then stimulated with 2 ng/mL EGF for 15 min. LAMP2 and EEA1 were then detected by immunofluorescence staining. White arrows indicate colocalisation. Scale bar: 10 μm. D: Quantification of the percentage of total EEA1 vesicles that colocalise with LAMP2 (in C). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). E: Cells were treated with 2 ng/mL EGF for 15 min before immunofluorescence against endogenous ATG16L1 and EEA1. Scale bar: 10 μm. F: Quantification of percentage of total EEA1 puncta that colocalise with ATG16L1 (in E). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). G: Cells stably expressing Flag-S-ATG16L1 were treated for 1 hr with either 100 μM monensin or 30 μM Dynasore, then stimulated with 2 ng/mL EGF for 15 min. Cells were then stained by immunofluorescence against EEA1 and Flag tag. Scale bar: 10 μm. H: Quantification of percentage of total EEA1 vesicles that colocalise with Flag-S-ATG16L1 (in G). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). I: Untreated control or sgAtg7 cells, or control cells pre-treated with 100 μM monensin 1 hr, stably expressing Flag-S-ATG16L1 were stimulated 20 ng/mL Alexa 555-EGF (555-EGF) for 15 min before fixation and immunofluorescence staining against Flag tag and EEA1. Cells were then imaged by structured illumination microscopy (SIM) and images were reconstructed in Nikon Elements software. Scale bar: 10 μm. J: Quantification of the percentage of EGF-EEA1 colocalised vesicles that stained triple-positive with ATG16L1 by SIM (in I). Due to the low throughput nature of this assay, the following cell numbers were counted: control untreated (9 cells), sgAtg7#1 (10 cells), sgAtg7#2 (9 cells), and control + monensin: (11 cells). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). K: Cells were treated with 2 ng/mL EGF for 15 min before immunofluorescence against endogenous WIPI2 and EEA1. Scale bar: 10 μm. L: Quantification of percentage of total EEA1 puncta that colocalise with WIPI2 (in K). Data information: White arrows indicate colocalisation. Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). A: Cells were treated for 15 min with 2 ng/mL EGF before fixation and immunofluorescence staining against EEA1 and p-TBK1. White arrows indicate colocalisation. Scale bar: 10 μm. B: Quantification of percentage of total EEA1 vesicles that colocalise with p-TBK1 (in A). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). C: Cells stably expressing Flag-S-ATG16L1 were pre-treated for 1 hr with TBK1 inhibitors (100 μM MRT68601 or 5 μM momelotinib). Control cells were also treated 100 μM monensin for 1 hr as indicated. All cells were stimulated for 15 min with 2 ng/mL EGF followed by fixation and immunofluorescence staining against Flag tag and EEA1. Scale bar: 10 μm.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). D: Quantification of total EEA1 vesicles that colocalise with Flag-S-ATG16L1 Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). E: Western blotting of shNf-1/shTp53 glial cells expressing gRNA sequences targeting Gal8.",
    "ncbi_link": "Atg7: 74244
Gal8: 56048
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "The following experiments were performed in glial shNf-1/shTp53 glial cells serum starved 4 hr before assaying. Cells were expressing either Cas9 alone (control) or Cas9 and sgRNA targeting Atg7 (sgAtg7 #1 or #2). F: Control and sgGal8 cells stably expressing Flag-S-ATG16L1 were treated 100 μM monensin for 1 hr and stimulated with 2 ng/mL EGF for 15 min before fixation and immunofluorescence staining against EEA1 and Flag tag. White arrows indicate colocalisation. Scale bar: 10 μm. G: Quantification of percentage of total EEA1 vesicles that colocalise with Flag-S-ATG16L1 in sgGal8 cells (in F). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: * p<0.05, ** p<0.01, *** p<0.001.",
    "ncbi_link": "Flag: 
ATG16L1: 77040
Atg7: 74244
Gal8: 56048
Nf-1: 18015
Tp53: 64058
Cas9: 901176"
  },
  {
    "caption": "A: Glial shNf-1/shTp53 control and sgAtg7 cells were serum starved 4 hr then stimulated with 20 ng/mL TexasRed-EGF (TxRed-EGF) for 30 min. Scale bar: 10 μm. B: Quantification of TxRed-EGF puncta per cell, relative to the number taken up by control cells (in A). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, *** p<0.001.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "C: Endocytosis rate of wild type (WT) EGFR was assayed in control, sgAtg7, or sgAtg16l1 glial shNf-1/shTp53 or EGFRvIII-expressing cells by cell surface biotinylation and one application of 2 ng/mL EGF for 15 min. Monensin treatment was added as indicated. Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, *** p<0.001.",
    "ncbi_link": "Atg16l1: 77040
Atg7: 74244
EGFR: 13649
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "D: Plasma membrane recycling rate of WT EGFR in control, sgAtg7, or sgAtg16l1 glial shNf-1/shTp53 or EGFRvIII-expressing cells was assayed by cell surface biotinylation and successive applications of 2 ng/mL EGF treatments for 15 min Monensin treatment was added as indicated. Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, *** p<0.001.",
    "ncbi_link": "Atg16l1: 77040
Atg7: 74244
EGFR: 13649
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "E: Glial shNf-1/shTp53 control and sgAtg7 cells stably overexpressing mCherry-Rab11 were serum starved 4 hr then stimulated with 20 ng/mL EGF for 15 min then fixed and stained by immunofluorescence against EGFR. White arrows indicate colocalisation. Scale bar: 10 μm. F: Quantification of Pearson's colocalisation coefficient between mCherry-Rab11 and EGFR (in E). Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, *** p<0.001.",
    "ncbi_link": "mCherry: 
Atg7: 74244
Nf-1: 18015
Tp53: 64058
Rab11: 8766"
  },
  {
    "caption": "Glial shNf-1/shTp53 sgAtg7 (A) cells were either left untreated (+serum) or serum starved (-serum) 4 hr then stimulated 2 ng/mL EGF for 15 min before analyses by western blotting.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "Glial shNf-1/shTp53 sgAtg16l1 (B) cells were either left untreated (+serum) or serum starved (-serum) 4 hr then stimulated 2 ng/mL EGF for 15 min before analyses by western blotting.",
    "ncbi_link": "Atg16l1: 77040
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "Glial shNf-1/shTp53 sgGal8 (C) cells were either left untreated (+serum) or serum starved (-serum) 4 hr then stimulated 2 ng/mL EGF for 15 min before analyses by western blotting.",
    "ncbi_link": "Gal8: 56048
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "D: Glial shNf-1/shTp53 control and sgAtg7 cells were serum starved 4 hr then stimulated with 2 ng/mL EGF for the indicated times before analysis of EGFR signalling pathway activity by western blotting. E: Phosphorylated:total protein ratios for EGFR and AKT calculated from densitometry analyses of western blots were made relative to their respective points of maximal stimulation (100%) (for EGFR: t=5 min in control cells and for AKT: t=7 min in control cells) Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "F: Glial shNf-1/shTp53 control and sgAtg7 cells were serum starved 4 hr with or without 20 ng/mL EGF 30 min stimulation before subcellular fractionation and analysis by western blotting.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "G: Radar chart indicating the relative levels of pAKT (pink line), pEGFR (light blue line), or total EGFR levels (dark blue line), in autophagy-deficient cell lines relative to their control counterparts. The following knockouts were introduced: glial cells (sgAtg7), HT29 (crATG7), MCF-7 (sgATG5), A549 (sgATG5), U2OS (sgATG5), and MEFs (Atg16l1-/-).",
    "ncbi_link": "Atg16l1: 77040
ATG5: 9474
Atg7: 74244
ATG7: 10533"
  },
  {
    "caption": "H: Control or sgAtg7 glial shNf-1/shTp53 cells were serum starved for 24 hr in the presence or absence of 20 ng/mL EGF. Quantification of the percentage of propidium iodide (PI)-positive cells is shown. Data information: Statistical analyses were performed on at least 3 independent experiments, where error bars represent SEM and p values represent a two-tailed Student's t test: NS p>0.05, * p<0.05, ** p<0.01.",
    "ncbi_link": "Atg7: 74244
Nf-1: 18015
Tp53: 64058"
  },
  {
    "caption": "HT29 cell survival 18h after treatment with TNF+BV-6+z-VAD-fmk to induce necroptosis. Cells expressed lentivirus constructs encoding 1-90 or 1-277 fragments of M45 and were cultured +/- the addition of coumermycin A1 to induce dimerisation. N=2 for M45-90 gyrase +/- coumermycin A1 and 4 for M45-277 gyrase and for empty vector, +/- coumermycin A1",
    "ncbi_link": "gyrase: 
M45: 3293809
M45-277: 3293809
M45-90: 3293809"
  },
  {
    "caption": "A-B. Wild-type and ΔnlpI cells were heated at a range of temperatures and the soluble components were labelled by TMT, combined and quantified by LC-MS, using the published 2D-TPP protocol (Mateus et al., 2018). Shown are volcano plots of two replicates depicting changes in: protein abundance (A) and thermostability (B). A local FDR (false discovery rate) <0.01 was set as a threshold for significance. Highlighted proteins: outer membrane proteins (OMPs, light green), β-barrel assembly machinery (BAMs, red), PG synthases/regulators (green), PG hydrolases and regulators (blue) and the Tol-Pal complex (violet). All other proteins were colored grey and not labelled to increase the plot clarity.",
    "ncbi_link": "nlpI: 947673"
  },
  {
    "caption": "B. Genetic interactions of nlpI with EPase genes. Strains were arrayed using a Rotor HDA replicator on Lennox LB agar plates and incubated for 12 h at 37°C. Each plate contained 384 colonies, 96 from the wildtype, single mutants and double mutants. An example of a 384 plate is shown. Double mutants were made twice, swapping the resistance markers to the two single mutants. Colony integral opacity was quantified as a fitness readout, using the image analysis software Iris (Kritikos et al., 2017). Bar plots shows the averaged values of 2 biological experiments, each having 96 technical replicates (i=2, n=192). The error bars represent the 95% confidence interval.",
    "ncbi_link": "nlpI: 947673"
  },
  {
    "caption": "C. nlpI deletion changes the morphology of EPase-mutant strains. The graph shows the cell width of single and double deletions strains (800 < n < 2000 cells). The box has a medium between 25 and 75%. The whiskers with the upper and lower vertical line indicating the 95 and 5%. The dots are individual points outside the 5 and 95% range. Above the graph are representative images of cells lacking MepS or PBP4 in combination with a deletion of NlpI. The scale bar equals 2 µm. Gene encoding protein legend: nlpI encodes NlpI, dacB encodes PBP4, pbpG encode PBP7, mepM encodes MepM, meps encodes MepS.",
    "ncbi_link": "dacB: 947693
PBP4: 947693
mepM: 946376
meps: 946686
MepS: 946686
nlpI: 947673
NlpI: 947673
pbpG: 946662"
  },
  {
    "caption": "D. Inducible mepS expression system (pBAD30) strongly overproduces MepS. Strains were grown in LB at 30°C and cells were collected at OD600≈0.4. The level of MepS contained in the membrane fraction was detected using purified anti-MepS antibody.",
    "ncbi_link": "mepS: 946686
MepS: 946686"
  },
  {
    "caption": "E. Visualization of the effect of MepS absence or its overexpression on cell width by phase contrast microscopy. Cultures were grown in LB at 30°C and aliquots of culture were taken at OD600≈0.1. The scale bar equals 5 μm.",
    "ncbi_link": "MepS: 946686"
  },
  {
    "caption": "G. Relative fitness of ΔnlpI, ΔmepS and ΔnlpIΔmepS mutants. Strains were arrayed using a Rotor HDA replicator on Lennox LB agar plates supplemented 10% sucrose, or LB agar plates containing 0 mM or 500 mM NaCl. Plates were incubated for 12 h at 37°C. Each plate contained 384 colonies, 96 from the wildtype, single mutants and double mutants.",
    "ncbi_link": "mepS: 946686
nlpI: 947673"
  },
  {
    "caption": "H. Cells of wildtype (WT), ΔnlpI, ΔmepS and ΔnlpIΔmepS containing multicopy plasmids with lacZ were grown onto CPRG indicator agar to assay envelope integrity. CPRG (yellow) cannot penetrate intact Gram-negative envelopes. Its conversion by intracellular β-galactosidase to CPR (red) indicates loss of envelope integrity.",
    "ncbi_link": "lacZ: 945006
β-galactosidase: 945006
mepS: 946686
nlpI: 947673"
  },
  {
    "caption": "B. Genetic interactions of NlpI with PG machineries. An example of a 384 plate is shown. Bar plots shows the averaged values of 2 experiments (i=2, n=192). Error bars denote the 95% confidence interval of the mean.",
    "ncbi_link": "NlpI: 947673"
  },
  {
    "caption": "C. NlpI deletion exacerbates the morphological defects of the PBP1B/LpoB-mutant strains. The graph shows the cell width of single and double deletions strains (800 < n < 2000 cells). The box has a medium between 25 and 75%. The whiskers with the upper and lower vertical line indicating the 95 and 5%. The dots are individual points outside the 5 and 95% range. Representative images of the strains are shown above the graph. The scale bar equals 2 µm. Gene encoding protein legend: nlpI encodes NlpI, mrcA encodes PBP1A, lpoA encodes LpoA, mrcB encodes PBP1B, lpoB encodes LpoB.",
    "ncbi_link": "lpoA: 947663
lpoB: 948536
LpoB: 948536
mrcA: 947907
mrcB: 944843
PBP1B: 944843
nlpI: 947673
NlpI: 947673"
  },
  {
    "caption": "A. Estimated number of molecules and molarity of PBP1a/LpoA and EPases. 1Numbers obtained by ribosomal profiling in rich growth medium (Li et al., 2014). 2Concentration of monomer. 3Decreases in the presence of NlpI (Singh et al., 2015). 4\"no change detected\". The periplasmic concentrations of proteins were estimated for a cell with periplasmic volume of 3.33 ×10-16 L, where 1 molecule corresponds to 5 nM.",
    "ncbi_link": "NlpI: 947673"
  },
  {
    "caption": "A Live cell imaging reveals that expression of GFP‐KSHV‐TK, but not GFP induces contraction of HeLa cells (see Supplementary Movies S1 and S2). The time from the start of imaging is indicated above each panel, and the scale bars represent 18 μm. Quantification of GFP‐KSHV‐TK‐induced cell contraction. The graphs show cell area (μm2) of cells expressing the indicated protein, and error bars represent SEM from three independent experiments in which n = 224 for GFP and n = 203 for GFP‐KSHV‐TK. ***P 0.001.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "A Co‐expression of GFP‐RhoN19 but not GFP inhibits RFP‐KSHV‐TK‐induced cell contraction. Graphs represent cell area (μm2) of KSHV‐TK, RhoN19 or KSHV‐TK and RhoN19 expressing cells. Error bars represent SEM from 3 independent experiments, n = 204 for KSHV‐TK, n = 223 for RhoN19 and n = 189 for KSHV‐TK and RhoN19.",
    "ncbi_link": "KSHV‐TK: 4961484
Rho: 9475///6093"
  },
  {
    "caption": "D GFP‐KSHV‐TK but not GFP induces the loss of phosphotyrosine, phospho‐FAK Y925 and phospho‐paxillin Y31 epitopes from focal adhesions.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "B Immunoblot analysis of BHK cells infected with MuHV‐4 and MuHV‐4 [g‐KSHV‐TK] or uninfected cells using antibodies against phosphotyrosine (p‐Tyr), GFP, MuHV‐4 TK, ORF17 (capsid) and glycoprotein N.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "C Immunofluorescence microscopy analysis of MuHV‐4‐ and MuHV‐4 [g‐KSHV‐TK]‐infected cells with the indicated antibodies reveals GFP‐KSHV‐TK expressed in the context of lytic infection (MuHV‐4 [g‐KSHV‐TK]) induces the loss of phospho‐FAK Y925 and paxillin Y31 from focal adhesions. White arrowheads indicate examples of infected cells expressing GFP‐KSHV‐TK or GFP (indicating WT MuHV‐4 infection, BAC+ virus).",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "B Scanning electron microscopy of HeLa cells expressing GFP or GFP‐KSHV‐TK‐DEAD.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "E Purified recombinant GST‐EBV‐TK, GST‐MuHV‐4-TK and GST‐KSHV‐TKimmunoblotted for phosphotyrosine and GST following a sequential dephosphorylation and kinase reaction.",
    "ncbi_link": "EBV‐TK: 
KSHV‐TK: 4961484
MuHV‐4-TK: 1497151"
  },
  {
    "caption": "F Purified recombinant GST‐KSHV‐TK and GST‐KSHV‐TK‐KINASE‐DEAD immunoblotted for phosphotyrosine and GST.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "F Immunoblot analysis of level of GTP‐bound and total RhoA in cells expressing the indicated GFP‐tagged KSHV‐TK proteins.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "A Immunoblot analysis reveals that GFP‐KSHV‐TK WT, Y2F and Y3F but not GFP‐KSHV‐TK‐DEAD associate with FAK.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "B GFP‐KSHV‐TK does not displace paxillin or zyxin from focal adhesions (white arrowheads) or induce contraction in the absence of FAK. Scale bar, 20 μm.",
    "ncbi_link": "FAK: 2185///5747"
  },
  {
    "caption": "C GFP‐KSHV‐TK does not induce loss of zyxin and p‐Tyr from focal adhesions or contraction of HeLa cells depleted of paxillin. Error bars represent SEM from three independent experiments, n = 196 for mock siRNA and n = 229 for paxillin siRNA; ***P 0.001. Scale bar, 20 μm.",
    "ncbi_link": "KSHV‐TK: 4961484
paxillin: 5829"
  },
  {
    "caption": "E Immunofluorescence microscopy analysis of phosphotyrosine epitopes in cells expressing GFP‐CrkII SH2, GFP‐CrkL SH2, RFP‐KSHV‐TK or a combination of CrkII/LSH2 and RFP‐KSHV‐TK. Arrowheads represent contracted KSHV‐TK‐expressing cells. The SH2 domains of CrkII or L block KSHV‐TK‐induced cell rounding. Scale bars, 20 μm.",
    "ncbi_link": "CrkII: 1398
KSHV‐TK: 4961484"
  },
  {
    "caption": "E Tyrosine phosphorylation of CrkII and CrkL is only upregulated in cells expressing GFP‐KSHV‐TK.",
    "ncbi_link": "KSHV‐TK: 4961484"
  },
  {
    "caption": "Atoh1 KD analysis. (G, H) Atoh1 shRNA was introduced to P5 mice EGL together with H2B-EGFP plasmid and immunostaining for NEUROD1 (Cyan) and KI67 (magenta) was performed 24 hrs later. Nuclei of electroporated cells were labeled with GFP (green). Images of Control (G) and Atoh1 KD (H). Arrows indicate the cells of interest where GFP signals are co-localized with NEUROD1 and KI67.",
    "ncbi_link": "Atoh1: 11921"
  },
  {
    "caption": "(I) Proportions of NEUROD1+, KI67+ cells (ND+GCPs) among the electroporated GCPs (GFP+, KI67+ cells) were increased in the Atoh1 KD mice. (J) Proportions of KI67+ cells (total GCPs) were not significantly changed. Student T-test was performed between Control (N=4) and Atoh1 shRNA (sh#1: N=3, sh#2: N=3). Bars and error bars are representing as Mean ± SEM. *p < 0.05, N.S.: Not Significant. Number of cells: 98,71,81 and 60 cells from N=4 mice (sclamble), 127,93 and 51 cells from N=3 mice (sh#1), 75,111,38 cells from N=3 mice (sh#2).",
    "ncbi_link": "Atoh1: 11921"
  },
  {
    "caption": "B. Immunostaining of P5 cerebellum with indicated antibodies. Boxplots of the intensity of CCND1 immuno-signal (B'''', normalized to the mean intensity of AT+GCPs). We measured the intensities of CCND1 in ATOH1+/NEUROD1- cells and NEUROD1+/ ATOH1- cells. ATOH1+/ NEUROD1+ cells were not included in this quantification. These boxplots are showing the median (central band), 25% / 75% quartiles (boxes) and the ranges (lower whiskers represent the regions of lower box - 1.5 * IQR (inter-quartile range), upper whisker represent the regions of upper box - 1.5 * IQR). Wilcoxon test were performed between AT+GCPs and ND+GCPs. ***p < 0.001.",
    "ncbi_link": "AT: 11921
ND: 18012"
  },
  {
    "caption": "C-F. Ccnd1 KD analysis. (C, D) Ccnd1 shRNAs together with H2B-EGFP plasmid were introduced to P5 mice EGL and immunostaining for ATOH1 (magenta) and KI67 (Cyan) was performed the following day. Nuclei of electroporated cells were labeled with GFP (yellow). Images of Control (C) and Ccnd1 KD (D). Arrows indicate the cells of interest where GFP signals are co-localized with ATOH1. (E) Proportions of ATOH1+, KI67+ cells (AT+GCPs) among the electroporated cells were decreased in the Ccnd1 KD mice. (F) Proportions of KI67+ cells (total GCPs) were not significantly changed. Student T-test was performed between Control (N=3) and Ccnd1 KD (sh#1: N=3, sh#2: N=3) mice. Bars and error bars are representing as Mean ± SEM. ***p < 0.001, N.S.: Not Significant. Number of cells: 52, 64 and 107 cells from N=3 mice (scramble), 72,79 and 75 cells from N=3 mice (sh#1), 84, 70 and 40 cells from N=3 mice (sh#2).",
    "ncbi_link": "Ccnd1: 12443"
  },
  {
    "caption": "G-K. Over-expression analysis of Ccnd1 with or without Cdk4. (G, H, I) Ccnd1 and Cdk4 expression plasmids were introduced to P5 mice EGL and immunostaining for ATOH1 (magenta) and KI67 (cyan) was performed the following day. Nuclei of electroporated cells were labeled with GFP (yellow). Images of Control (G), CCND1 over expression (H) and CCND1 and CDK4 over expression (I). Arrows indicate the cells of interest where GFP signals are co-localized with ATOH1. (J) Proportions of ATOH1+, KI67+ cells (AT+GCPs) among the electroporated cells were not significantly changed between Control and CCND1. Forced expression of CCND1 and CDK4 (4D) significantly increased the proporations of AT+GCPs compared to Control. (K) Proportions of KI67+ cells (total GCPs) were not significantly changed. Tukey-Kramer test was performed on Control (N=6), CCND1 (N=4), CCND1 and CDK4 (N=3). Bars and error bars are representing as Mean ± SEM. **p < 0.01, N.S.: Not Significant. Number of cells: 52, 64, 107,244,127 and 146 from N=6 mice (Control), 126, 137, 80 and 336 from N=4 mice (Ccnd1), 212, 143 and 38 from N=3 mice (4D).",
    "ncbi_link": "Ccnd1: 12443
CCND1: 12443
Cdk4: 12567
CDK4: 12567"
  },
  {
    "caption": "C. N2a cells transfected with Atoh1-GST plasmids were treated with DMSO(Control), Palbociclib (Palb) or Palb and 10 uM MG132 (MG132) for 6hrs before harvest. Lysates of N2a were subjected to immunoblotting with anti-Atoh1 or β-actin. Quantification of relative ATOH1 to the β-ACTIN (right panel). Tukey-Kramer test was performed between Control, Palb, MG132. Bars and error bars are representing as Mean ± SEM from three trials of each condition. ***p < 0.001, *p < 0.05, N.S.: Not Significant. Three slots of each experimental condition represent the three biological replicants of each condition.",
    "ncbi_link": "GST: 
Atoh1: 11921"
  },
  {
    "caption": "G. Atoh1 expression plasmids were transfected into N2a cells with Ccnd1 and Cdk4 expression plasmids (4D). N2a cells were treated with 10 nM, 100 nM, 1000 nM Palb for 6 hrs before harvest. Lysates from N2a cells were subjected to immunoblotting with anti-Atoh1, p-S309-Ab and β-actin. Quantification of relative ATOH1 to the β-ACTIN (right panel). Tukey-Kramer test was performed between 0, 10, 100, 1000nM. Bars and error bars are representing as Mean ± SEM from three trials of each condition. **p < 0.01, *p < 0.05, N.S.: Not Significant.",
    "ncbi_link": "Atoh1: 11921
Ccnd1: 12443
Cdk4: 12567"
  },
  {
    "caption": "B. Lysates of N2a cells transfected with either WT or a phospho-mimic form of ATOH1 (S309D) were immunoblotted with anti-Atoh1 or β-actin. Quantification of relative levels of ATOH1 to the β-ACTIN (right panel). Mean± s.e.m. Student T-test between WT and S309D was performed. ***p < 0.001. Three slots of each experimental condition represent the three biological replicants of each condition.",
    "ncbi_link": "ATOH1: 11921"
  },
  {
    "caption": "Rescue experiment of Atoh1 KD with WT or S309A form of Atoh1. (F-I) Scramble (Control), Atoh1 shRNA (Atoh1 KD), shRNA and WT (KD + WT) or shRNA and S309A (KD + S309A) plasmids were introduced to P5 mice EGL with H2B-EGFP plasmid and immunostaining for NEUROD1(magenta) was performed at P7. Nuclei of electroporated cells were detected by GFP (green). Arrows indicate the cells of interest which GFP signals are not co-localized with NEUROD1 (AT+GCPs).",
    "ncbi_link": "Atoh1: 11921
AT: 11921"
  },
  {
    "caption": "B-D. Overexpression analysis of PROX1. (B, C) Prox1 expression plasmids were introduced to mouse P5 EGL and immunostaining for CCND1 (magenta) was performed the following day. Nuclei of electroporated cells were detected with GFP (green). Images of Control (B), PROX1 overexpression (C). Arrow heads indicates the CCND1 positive cells. White lines are representing as pial surfaces. (D) The proportion of CCND1-positive cells among the electroporated cells. Bars and error bars are representing as Mean ± SEM. Student T-test between Control (N=3) and PROX1 overexpression (N=3). **p < 0.01. Number of cells 382, 147 and 88 cells from N=3 mice (control), 187, 108 and 94 cells from N=3 mice (Prox1 OE).",
    "ncbi_link": "PROX1: 19130
Prox1: 19130"
  },
  {
    "caption": "E-G. Prox1 acute KO analysis. (E, F) Expression plasmids of Cre recombinase were introduced to P5 EGL of Prox1fl/fl mice and immunostaining for CCND1 (magenta) was performed at P8. Nuclei of electroporated cells were labeled with GFP (green). Images of H2B-GFP electroporation (E, Control), Cre electroporation (F, Cre). Arrows indicate the cells of interest where GFP signals are co-localized with CCND1. (G) The proportions of CCND1+ cells among the electroporated cells. Bars and error bars are representing as Mean ± SEM. Student T-test between Control (N=3) and Cre (N=3). **p < 0.01. Number of cells: 238, 129 and 529 cells from N=3 mice (Control), 169, 210 and 216 cells from N=3 mice (Cre).",
    "ncbi_link": "Cre: 2777477
Prox1: 19130"
  },
  {
    "caption": "H-K. Rescue experiment of Prox1 with Ccnd1 and Cdk4-expressing plasmids. (H-J) Prox1 expressing plasmids were introduced with Ccnd1 and Cdk4 expression plasmids (Prox1+4D) to P5 EGL together with H2B-GFP plasmid. Immunostaining for ATOH1 (magenta) was performed the following day. Nuclei of electroporated cells were detected by GFP (green). Arrows indicate the cells of interest where GFP signals are co-localized with ATOH1. (K) Proportions of ATOH1+ cells (AT+GCPs) among the electroporated cells. The Tukey-Kramer test was performed on Control (N=6), Prox1 (N=3) and Prox1+4D (N=4) mice. **p < 0.01, *p <0.05, N.S.: Not Significant. Bars and error bars are representing as Mean ± SEM. Control value is the same as Fig 2G,K. Number of cells: 54, 72 and 59 cells from N=3 mice (Prox1), 26, 53, 68 and 53 cells from N=4 mice (Prox1+4D).",
    "ncbi_link": "Ccnd1: 12443
Cdk4: 12567
Prox1: 19130"
  },
  {
    "caption": "L. ChIP assay in P7 mouse cerebellum with anti-Prox1 or goat IgG as a negative control. Primer set used in this experiment was designed to amplify Ccnd1 promoter region. M-R. Administration of Valproic acid (VPA) to electroporated mice. (M) Expression plasmids of Prox1 were introduced to P5 EGL and VPA or Saline was administered intraperitoneally 2 days after electroporation. Immunostaining for CCND1 (magenta) was performed the day following the last VPA treatment. Nuclei of electroporated cells were detected with GFP (green). Arrows indicate the cells of interest where GFP signals are co-localized with CCND1. (N-Q) Images of H2B-GFP with Saline (N), PROX1 with Saline (O), H2B-GFP with VPA (P), and PROX1 with VPA (Q). (R) The relative proportions of CCND1+ cells among the electroporated cells (normalized to the Control).Tukey-Kramer test among Control+saline (N=4), PROX1+saline (N=3), Control +VPA (N=3) and PROX1 +VPA (N=3). Bars and error bars are representing as Mean ± SEM. **p < 0.01, *p <0.05, N.S.: Not Significant. Number of cells: 120, 488, 934 and 211 from N=4 mice (Control+saline), 630, 356 and 545 from N=3 mice (Control+VPA), 363, 127 and 219 from N=3 mice (Prox1+saline), 110, 116 and 202 from N=3 mice (Prox1+VPA).",
    "ncbi_link": "Ccnd1: 12443
CCND1: 12443
Prox1: 19130"
  },
  {
    "caption": "L-P. Over-expression analysis of WT or S309D form of Atoh1. (L) Expression plasmids of either WT or S309D form of Atoh1 were introduced to P10 mice EGL and immunostaining for KI67 (magenta) was performed in P16 mouse cerebellum. Nuclei of electroporated cells were detected by GFP (green). Images of H2B-GFP (M, Control), WT(N) and S309D (O). Arrows indicate the cells of interest where GFP signals are co-localized with KI67. (GCPs). (P) Proportions of KI67+ cells among the electroporated cells. Tukey-Kramer test among Control (N=3), Atoh1 WT (N=3) and Atoh1 S309D (N=3). Bars and error bars are representing as Mean ± SEM. *p <0.05. Number of cells: 43, 68 and 46 from N=3 mice (Control), 104, 215 and 157 cells from N=3 mice (WT), 242, 119 and 111 cells from N=3 mice (S309D).",
    "ncbi_link": "Atoh1: 11921"
  },
  {
    "caption": "D-F. Over-expression analysis of the activated form of β-catenin (βcat S33Y). (D, E) Expression plasmids of βcat S33Y were introduced to P5 mice EGL and immunostaining for PROX1 (magenta) was performed the following day. Nuclei of electroporated cells were detected with GFP (green). Images of H2B-GFP (D, Control) and βcat S33Y (E, S33Y). Arrows indicate the cells of interest where GFP signals are co-localized with PROX1. (F) Proportions of PROX1-positive cells in electroporated cells. Bars and error bars are representing as Mean± SEM. Student T-test between Control and S33Y was performed. ***p < 0.001. Number of cells: 89, 90 and 55 cells from N=3 mice (Control), 32, 111 and 56 cells from N=3 mice (S33Y).",
    "ncbi_link": "β-catenin: 12387
βcat: 12387"
  },
  {
    "caption": "J-L. Expression plasmids of βcat S33Y were introduced with or without Ccnd1 and Cdk4 expression plasmids (4D) to P5 mice EGL and immunostaining for ATOH1 (magenta) was performed the following day. Nuclei of electroporated cells were detected by GFP (green). Images of βcat S33Y (J, S33Y) and βcat S33Y with Ccnd1 and Cdk4 (K). Arrows indicate the cells of interest where GFP signals are co-localized with ATOH1.Proportions of ATOH1+ cells (AT+GCPs) among the electroporated cells. Control value is the same as Fig 2G-K. Bars and error bars are representing as Mean± SEM. Tukey-Kramer test was performed between Control, S33Y and S33Y+4D (L). ***p < 0.001, N.S: Not Significant. Number of cells: 123, 138 and 113 cells from N=3 mice (S33Y), 144, 223 and 180 cells from N=3 mice (S33Y+4D).",
    "ncbi_link": "Ccnd1: 12443
Cdk4: 12567
βcat: 12387"
  },
  {
    "caption": "RT-PCR analysis of TTN exon 326 transcripts from DCM cardiomyocytes transiently transfected with 2OMePS-AON1, 2OMePS-AON3, and 2OMePS-AON1 + 3.",
    "ncbi_link": "TTN: 7273"
  },
  {
    "caption": "RT-PCR analysis (left) and representative direct sequencing (right) of TTN exon 326 transcripts from DCM cardiomyocytes infected with the U7snRNA-TTNAONs-IRES-GFP lentiviral vector carrying the AON1 and 3 sequences (TTN-AON) or with a control vector (U7snRNA-ScrAONs-IRES-GFP).",
    "ncbi_link": "TTN: 7273"
  },
  {
    "caption": "Mass spectrometry-based analysis of titin peptides in cells infected with the U7snRNA-ScrAONs-IRES-GFP (Scr-AON) and U7snRNA-TTNAONs-IRES-GFP (TTN-AON) vectors. Unsupervised hierarchical clustering identified a cluster significantly enriched in peptides mapping to exon 326 that was down-regulated in DCM Scr-AON cardiomyocytes compared to CTR Scr-AON cardiomyocytes (n = 3, P = 9.03E−8, Fisher's exact test, FDR = 0.04, top). Down-regulation of exon 326 was also detected in DCM TTN-AON cells when compared to DCM Scr-AON cells (n = 3, P = 0.02, Fisher's exact test, bottom).",
    "ncbi_link": "TTN: 7273"
  },
  {
    "caption": "Percentage of perinuclear, fully, and peripherally organized single cardiomyocytes from two CTR and two DCM iPSC clones after infection with the U7snRNA-ScrAONs-IRES-GFP and U7snRNA-TTNAONs-IRES-GFP lentiviruses. Statistical difference was tested using the two-sided chi-squared test (CTR1 Scr-AON: n = 190, CTR2 Scr-AON: n = 200, DCM1 Scr-AON: n = 221, DCM2 Scr-AON: n = 115, CTR1 TTN-AON: n = 223, CTR2 TTN-AON: n = 187, DCM1 TTN-AON: n = 171, DCM2 TTN-AON: n = 243; ***P = 4.22E−15 CTR Scr-AON versus DCM Scr-AON; ***P = 4.61E−02 DCM Scr-AON versus DCM TTN-AON). No significant differences were observed comparing CTR Scr-AON and CTR TTN-AON groups.",
    "ncbi_link": "TTN: 7273"
  },
  {
    "caption": "qRT-PCR analysis of SRF target genes (MYH6, MYH7 and ACTC1) in CTR and DCM single cardiomyocytes under basal condition (no infection, NI) and after infection with control U7snRNA-ScrAONs-IRES-GFP (Scr-AON) and the U7snRNA-TTNAONs-IRES-GFP (TTN-AON) lentiviruses. Statistical difference was tested using the two-sided Student's t-test (**P = 0.009, CTR Scr-AON versus DCM Scr-AON; *P = 0.04, DCM Scr-AON versus DCM TTN-AON for MYH6; **P = 0.002, CTR Scr-AON versus DCM Scr-AON; **P = 0.002, DCM Scr-AON versus DCM TTN-AON for MYH7; **P = 0.004, CTR Scr-AON versus DCM Scr-AON; *P = 0.02, DCM Scr-AON versus DCM TTN-AON for ACTC1). No significant differences were observed comparing the CTR NI, CTR Scr-AON and CTR TTN-AON groups and comparing the DCM NI and DCM Scr-AON groups. Expression values were relative to CTR Scr-AON, normalized to GAPDH, and presented as mean ± SEM, n = 3.",
    "ncbi_link": "GAPDH: 
ACTC1: 70
MYH6: 4624
MYH7: 4625
TTN: 7273"
  },
  {
    "caption": "Immunofluorescence images showing normal (a, b, e, f, i, l, o, p) and altered (c, d, g, h, m, n, q, r) intracellular distribution of SRF (a and b, nuclear; c and d, cytoplasmic), MURF2 (e and f, sarcomeric; g and h, nuclear), Nbr1 (i and l, sarcomeric; m and n, diffused), and SQSTM1/p62 (o and p, sarcomeric; q and r, diffused) in representative single cardiomyocytes (left). Sarcomeres are marked by α-actinin. On the right, percentage of CTR and DCM cardiomyocytes showing cytoplasmic expression of SRF, nuclear accumulation of MURF2, and diffused expression of Nbr1 and of SQSTM1/p62 after infection with control U7snRNA-ScrambleAONs-IRES-GFP (Scr-AON) and the U7snRNA-TTNAONs-IRES-GFP (TTN-AON) lentiviruses (right). Data represent mean values ± SEM from two control and two DCM clones. Statistical difference was tested using the two-sided chi-squared test (CTR Scr-AON: n = 874, n = 874, n = 882 and n = 890, CTR TTN-AON: n = 880, n = 990, n = 878 and n = 890, DCM Scr-AON: n = 890, n = 887, n = 884 and n = 886, DCM TTN-AON: n = 900, n = 875, n = 899 and n = 891 for SRF, MURF2, Nbr1 and SQSTM1/p62, respectively; *P = 0.01, CTR Scr-AON versus DCM Scr-AON; *P = 0.04, DCM Scr-AON versus DCM TTN-AON for SRF; *P = 0.02, CTR Scr-AON versus DCM Scr-AON; *P = 0.04, DCM Scr-AON versus DCM TTN-AON for MURF2; *P = 0.03, CTR Scr-AON versus DCM Scr-AON; *P = 0.03, DCM Scr-AON versus DCM TTN-AON for Nbr1; **P = 0.009, CTR Scr-AON versus DCM Scr-AON; *P = 0.01, DCM Scr-AON versus DCM TTN-AON for SQSTM1/p62). No significant differences were observed comparing CTR Scr-AON and CTR TTN-AON groups. Scale bars, 50 μm.",
    "ncbi_link": "TTN: 7273"
  },
  {
    "caption": "B, C Immunofluorescence images of sarcomeric α-actinin and myosin (B) and assessment of cardiac function (C) in homozygous Ttn knock-in embryos cultured for 24 h after mScrAON and mTtnAON transient transfection (n = 3 per group) or lentivirus delivery (n = 7 per group). Scale bars, 10 μm.",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "D Electron microscopy analysis in Ttn knock-in embryos cultured for 24 h after mScrAON and mTtnAON transient transfection. mTtnAON treatment of homozygous embryos rescued myofibril formation (left, black arrows), resulting in thicker filaments (right).",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "Echocardiographic analysis of adult knock-in mice. Statistical difference was tested using the two-sided Student's t-test (WT: n = 6, HET: n = 6; HET + vPMO-mScrAON: n = 10 and HET + vPMO-mTtnAON: n = 14; *P = 0.013, HET versus HET + vPMO-mTtnAON and *P = 0.02, HET + vPMO-mScrAON versus HET + vPMO-mTtnAON for LVEDD differences; **P = 0.006, HET versus HET + vPMO-mTtnAON and *P = 0.02, HET + vPMO-mScrAON versus HET + vPMO-mTtnAON for LV-EF differences; *P = 0.03, HET versus HET + vPMO-mTtnAON and *P = 0.04, HET + vPMO-mScrAON versus HET + vPMO-mTtnAON for IVSd differences; **P = 0.001, HET versus HET + vPMO-mTtnAON and *P = 0.03, HET + vPMO-mScrAON versus HET + vPMO-mTtnAON and for PWd differences). No significant differences were observed among groups at day 0 and day 7. Data represent mean values ± SEM.",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "Masson's trichrome staining of heart sections from HET animals injected with vPMO-mScrAONs and vPMO-mTtnAON. Scale bars, 1 mm.",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "Fluorescence in situ hybridization (FISH) of heart muscle tissue from adult knock-in mice with a probe complementary to vPMO-mTtnAON. Scale bars, 250 and 50 μm (magnification).",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "RT-PCR analysis of Ttn exon 326 transcripts from heart tissue of untreated WT and HET animals and vPMO-mScrAON- and vPMO-mTtnAON-treated mice (left). Representative direct sequencing of Ttn exon 326 transcripts from vPMO-mTtnAON-treated HET heart tissue (right).",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "Mass spectrometry-based analysis of titin peptides in adult knock-in mice injected with vPMO-mScrAONs and vPMO-mTtnAONs. Unsupervised hierarchical clustering identified a cluster enriched in exon 326 peptides that was down-regulated in vPMO-mTtnAON-treated animals compared to vPMO-mScrAON-treated littermates. Another cluster enriched in C-terminal peptides was up-regulated in the vPMO-mTtnAON group compared to the vPMO-mScrAON group (n = 3, P = 0.02, Fisher's exact test, FDR = 0.04).",
    "ncbi_link": "Ttn: 22138"
  },
  {
    "caption": "B, C, Analysis of GFP transfer after transplantation of Nrl::GFP donor photoreceptors into wildtype C57BL/6J (B) and Nrl-/- (C) recipient retinas after 14 (wt, n=9; Nrl-/-, n=7) and 21 (wt, n=6; Nrl-/-, n=4) and 90 (wt, n=5; Nrl-/-, n=4) days. Tissue is stained for GFP and nuclei (Hoechst). In this and all following figures, donor cells (D) are located above, and acceptor cells with GFP (A) are located below the outer limiting membrane (white dashed line), which delimits the apical border of the outer nuclear layer (ONL). In wildtype recipients, donor cells are typically located above the outer segment region (between the grey dashed lines). In Nrl-/- recipients, donor cells are located in the inner segment (IS) region. Plotted is the ratio of the numbers of GFP+ photoreceptors in the ONL (acceptor photoreceptors) and GFP+ donor photoreceptors in the subretinal space (SRS) over time.",
    "ncbi_link": "Nrl: 18185"
  },
  {
    "caption": "F, Co-transplanted P3-4 Crx::Cre and P3-5 ROSAmT/mG donor photoreceptors into C57BL/6J recipient retinas show Cre reporter gene induction in donor cells located in the SRS 14 days post-transplantation.",
    "ncbi_link": "Cre: 2777477
Crx: 12951
ROSA: 14910"
  },
  {
    "caption": "A-C, Combined FISH and IHF to detect GFP (A, B) and GNAT1 (C) 21 days post-transplantation of Nrl::GFP photoreceptors into C57BL/6J (A) and Nrl-/- (B, C) recipients.",
    "ncbi_link": "Nrl: 18185"
  },
  {
    "caption": "F-K, FISH and IHF for GFP and GFP transcripts in C57BL/6J recipients transplanted with lentiviral-infected donor cells expressing cytoplasmic GFP (Lenti -GFP) (F, I) and nuclear-localized GFP (Lenti-nls-GFP) (G, J). H, MT index for cytosolic (Lenti-GFP, n=5) and nuclear localized (Lenti-nls-GFP, n=3). K, Quantification of transcripts in donor and acceptor photoreceptors. (Lenti-GFP, n=6 images from 3 transplanted animals; Lenti-nls-GFP, n=8 images from 4 transplanted animals).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A, Maximum intensity projection of a confocal micrograph of a cryostat section from a Nrl-/- recipient retina 21 days after transplantation with Nrl::GFP donor photoreceptors, showing protrusions (pink arrows) connecting donor and acceptor photoreceptors.",
    "ncbi_link": "Nrl: 18185"
  },
  {
    "caption": "D, E, Left: 3D reconstruction of two-photon (D) and light sheet microscopy images of intact cleared ROSAmT/mG eye showing that GFP+-donor and -acceptor photoreceptors are in the same area. D, Right: A high magnification image showing GFP+-donor and -acceptor photoreceptors connected by protrusions (pink arrows). E, Right: In detail, donor and acceptor photoreceptors also appear connected through cell protrusions (pink arrow).",
    "ncbi_link": "ROSA: 14910"
  },
  {
    "caption": "B, Nrl::GFP donor photoreceptors transplanted in a Prphr2-/- recipient retina exhibit polarized Prphr2 expression (yellow arrow) on the apical side of the donor photoreceptor. Basal protrusions (pink arrows) indicate donor protrusions that contact the host retina.",
    "ncbi_link": "Prphr2: 19133"
  },
  {
    "caption": "A, B, Examples of live Nrl::GFP and C57BL/6J retinal cultures showing actin+ (SirActin) and GFP+ (A) and tubulin+ (ViaFluor) and MitoTracker Green+ (MTG) protrusions (B) connecting photoreceptors. DIC, differential interference contrast microscopy.",
    "ncbi_link": "SirActin: "
  },
  {
    "caption": "C, Confocal microscopy image of cryostat sections of C57BL/6J recipient retinas 21 days after transplant of C57BL/J6 photoreceptors infected with empty vector (n=5), RHOA overexpression (RHOA OE) (n=7) or RAC1 dominant negative (RAC1 DN) (n=7) lentiviruses. Quantification of MT in retinas transplanted with control, RHOA and RAC1 DN lentiviruses.",
    "ncbi_link": "RAC1: 19353
RHOA: 11848"
  },
  {
    "caption": "D, GFP staining of whole-mounted retinas after transplantation with control, RHOA and RAC1 DN lentivirus infected donor cells (n=4 per group). Quantification shows a significant reduction in the average protrusion length per cell and in the total protrusion length per cell after RHOA OE and RAC1 DN infection compared to the empty vector control.",
    "ncbi_link": "RAC1: 5879
RHOA: 387"
  },
  {
    "caption": "(A) Expression in E. coli and purification of human GS (hGS). Protein was separated by SDS-PAGE and stained with Coomassie Blue dye. M: marker Precision Plus Protein Dual Color Standard (Biorad). From right Lanes 1-4: E. coli Bl21(DE3) cells containing the expression vector without (lanes 1 and 2) and with (lanes 3 and 4) the coding sequence of hGS. Samples were taken immediately before (lanes 1 and 3) and 3,5 h later (lanes 2 and 4) the induction of expression with isopropil-β-D-1-tiogalattopiranoside (IPTG) 0.7mM. The same number of bacteria was analyzed in each sample. Lane 5: isolated and purified inclusion bodies (4 μg). Adiacent boxed lane: Western Blotting analysis of GS.",
    "ncbi_link": "hGS: 2752"
  },
  {
    "caption": "Evaluation of M1 markers in macrophages by real-time PCR. Fold change of TNFA, CD80, CXCL9, and CXCL10 mRNA in IL10, MSO- and glufosinate (10 and 20µM)- stimulated IL10 macrophages (n=3). Evaluation of M2 markers in macrophages by real-time PCR. Fold change of MRC1, MSR1, mRNA in IL10, MSO- and glufosinate (10 and 20µM)- stimulated IL10 macrophages (n=3).",
    "ncbi_link": "CD80: 941
CXCL10: 3627
CXCL9: 4283
MRC1: 4360
MSR1: 4481
TNFA: 7124"
  },
  {
    "caption": "Evaluation of M2 markers in macrophages by real-time PCR. Fold change of CCL17 and CCL18 mRNA in IL10, MSO- and glufosinate (10 and 20µM)- stimulated IL10 macrophages (n=3).",
    "ncbi_link": "CCL17: 6361
CCL18: 6362"
  },
  {
    "caption": "Evaluation of M1 markers in macrophages following HIF1α inhibition by real-time PCR. Fold change of TNFA, CXCL10, CD86 mRNA in IL10 alone or glufosinate (10 and 20µM)- and acriflavine/glufosinate (10 and 20µM)- IL10 macrophages (n=3).",
    "ncbi_link": "CD86: 942
CXCL10: 3627
TNFA: 7124"
  },
  {
    "caption": "Evaluation of M1 markers in macrophages following HIF1α inhibition by real-time PCR. Fold change of CD80 and CXCL9 mRNA in IL10 alone or glufosinate (10 and 20µM)- and acriflavine/glufosinate (10 and 20µM)- IL10 macrophages (n=3). Evaluation of M2 markers in macrophages following HIF1α inhibition by real-time PCR. Fold change of MRC1, MSR1, and CCL18 mRNA in IL10, glufosinate (10 and 20µM)- and acriflavine/glufosinate (10 and 20µM)- IL10 macrophages (n=3).",
    "ncbi_link": "CCL18: 6362
CD80: 941
CXCL9: 4283
MRC1: 4360
MSR1: 4481"
  },
  {
    "caption": "RT-PCR quantification of M2 (Ccl22, Arg1 and Ccl17) (I) markers in vehicle and glufosinate treated mice (n=4).",
    "ncbi_link": "Arg1: 11846
Ccl17: 20295
Ccl22: 20299"
  },
  {
    "caption": "RT-PCR quantification of M1 (Tnfa, Cxcl9, Nos2, Cd86 and Cd80) (J) markers in vehicle and glufosinate treated mice (n=4).",
    "ncbi_link": "Cd80: 12519
Cd86: 12524
Cxcl9: 17329
Nos2: 18126
Tnfa: 21926"
  },
  {
    "caption": "(N) RT-PCR quantification of M2 (Arg1 and Cxcr4) and M1 (Cxcl9 and Nos2) markers in vehicle and glufosinate (20mg/kg) treated mice (n=6).",
    "ncbi_link": "Arg1: 11846
Cxcl9: 17329
Cxcr4: 12767
Nos2: 18126"
  },
  {
    "caption": "GFP+ CTCs amount in blood, expressed as GFP expression levels, was determined by qPCR (n=8) (K).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(O) GFP+ cancer cells amount in lungs, expressed as GFP expression levels, was determined by qPCR in vehicle and glufosinate (10mg/kg) treated mice (n=8). The results were normalized to the vehicle group.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A and B) atg8a mutants exhibiting a striking positive staining for Ref(2)P and ubiquitin staining in all the regions of the adult brain. As it is shown in high magnification of the optic lobe (medulla region; B), Ref(2)P- and ubiquitin-positive aggregates are observed (arrows). Genotypes: (A and B) atg8aKG07569/Y",
    "ncbi_link": "atg8a: 32001"
  },
  {
    "caption": "(C) Normal phenotype is observed in β2 and 6 dominant-negative temperature-sensitive mutants at 25°C. (D) Accumulation of Ref(2)P- and ubiquitin-positive aggregates are observed in β2 and 6 mutants at 29°C (arrows). (C and D) elavGal4/+; UAS-β6/+; UAS-β2/+",
    "ncbi_link": "elav: 31000
β2: 39628
β6: 39855"
  },
  {
    "caption": "(E and F) double mutants for atg8a and ref(2)P loss-of-function alleles lacking the PB1 (E) or UBA (F) domain do not form ubiquitinated protein aggregates. Ubiquitin exhibits a cytoplasmic staining pattern (arrows). Genotypes: (E) atg8aKG07569/Y; ref(2)Pod2/ref(2)Pod2, and (F) atg8aKG07569/Y; ref(2)Pod3/ref(2)Pod3.",
    "ncbi_link": "atg8a: 32001
ref(2)P: 35246"
  },
  {
    "caption": "(A and B) Protein aggregates in atg8aKG07569 mutants exhibit sequestosome morphology and are positively labeled for Ref(2)P (A) and ubiquitin (B). Protein aggregates are surrounded by small electron-dense vesicles (arrows).",
    "ncbi_link": "atg8a: 32001"
  },
  {
    "caption": "(C) Western blot analysis of cell lysates of wild type and atg8aKG07569 young adult heads demonstrating a significant increase of Ref(2)P protein levels in atg8aKG07569 flies.",
    "ncbi_link": "atg8a: 32001"
  },
  {
    "caption": "(D, left) Ref(2)P protein migration profile in ref(2)P loss-of-function alleles. Ref(2)P mutant protein for the PB1 domain has an apparent molecular mass of 85 kD (ref(2)Pod2/ref(2)Pod2) and the Ref(2)P mutant protein for the UBA domain has an apparent molecular mass of 69 kD (ref(2)Pod3/ref(2)Pod3). (D, right) Western blot analysis of insoluble protein fractions of adult heads of double mutants for atg8a and ref(2)P probed for ubiquitin. Genotypes: (1) atg8aKG07569/Y; ref(2)Pod2/Cyo, (2) atg8aKG07569/Y; ref(2)Pod2/ref(2)Pod2, (3) atg8aKG07569/Y; ref(2)Pod3/CyO, and (4) atg8aKG07569/Y; ref(2)Pod3/ref(2)Pod3. The insoluble ubiquitinated protein profile of the double mutants is diminished compared with the one of the respective control heterozygous for ref(2)P.",
    "ncbi_link": "atg8a: 32001
ref(2)P: 35246"
  },
  {
    "caption": "(E and F) Neuronal cells mutant for atg1 (green) accumulate Ref(2)P- (E) and ubiquitin-positive (F) structures (arrows), whereas the normal surrounding cells do not exhibit positive staining. Genotypes: (E and F) yw/UAS-CD8-GFP, hs-flp; tubGal4/+; atg1Δ3D, FRT80/tubGal80, FRT80",
    "ncbi_link": "atg1: 39454"
  },
  {
    "caption": "(G) Confocal micrographs of the optic lobe (medulla region) of young flies expressing a mutated form of human tau protein exhibiting Ref(2)P- and tau-positive aggregates (arrows). Genotypes: (G) elav/+;UAS-E14/+.",
    "ncbi_link": "elav: 31000
tau: 4137"
  },
  {
    "caption": "A. EGFR (pY1068, left), Akt (pS473, middle) and Erk (pT202 and pY204, right) phosphorylation response in WT (red) compared to p22phox-KO (green) MCF7 cells as function of EGF concentration (ng/ml; nM) upon 5' stimulation with different doses of EGF-Alexa647 quantified from Western blot analysis. N=4 biological replicates with mean±SD, P:unpaired two-tailed t-test. B. Same as (A) comparing WT (red) to RPTPγ-KO (blue) MCF7 cells. N=3 biological replicates with mean±SD, P: unpaired two-tailed t-test. C. Quantitative Western blot analysis as in (A) comparing WT (red) and RPTPγ-KO (blue) MCF7 cells after EGF stimulus (20, 80, 160 ng/ml from (B), left column: w/o gef.) to the cells from the corresponding cell line treated with 10 μM of the EGFR-inhibitor Gefitinib for 1 h and the indicated EGF concentration for the last 5' (ng/ml). N=3 biological replicates with mean±SD, P: unpaired two-tailed t-test. D.",
    "ncbi_link": "p22phox: 1535
RPTPγ: 5793"
  },
  {
    "caption": "A. Left panel: comparison of normalized EGF-Alexa647 (160 ng/ml; 5') fluorescence intensity bound to individual endogenous EGFR expressing MCF10A (yellow), to exogenous EGFR-mCitrine expressing EmCit_MCF7 cells (black) and WT MCF7 cells (red); Right panel: normalized EGF-Alexa647 fluorescence plotted against normalized EGFR-mCitrine fluorescence intensity in WT (red) and EmCit_MCF7 (black, with 2nd order polynomal fit: grey line) cells. N=3 biological replicates, n>75 cells, mean±SD.",
    "ncbi_link": "mCit: 
mCitrine: 
EGFR: 1956"
  },
  {
    "caption": "D. Gray: αL upon each administered dose for individual EmCit_MCF7 cells to cumulative doses of EGF-Alexa647 (2.5-640 ng/ml). N=3 biological replicates, n=13 cells. Black: EGF-Alexa647 bound to WT MCF7 cells at the indicated concentrations normalized to the mean fluorescence intensity at 160 ng/ml EGF-Alexa647 (Fig 1E; mean±SD, N=5 biological replicates, n=16-19 fields of view).",
    "ncbi_link": "mCit: "
  },
  {
    "caption": "F. Left: EGFR- (pY1068-) phosphorylation response in WT MCF7 cells obtained from western blots normalized to maximal phosphorylation obtained by inhibiting all phosphatases by 0.33 mM pervanadate (N=6; red symbols with mean±SD and fit to the hill equation (solid line)) at 0 (plotted as 0.001 to fit the logarithmic x-axis), 0.5, 1, 2, 5, 10, 20, 40 and 80 ng/ml plotted against corresponding αL (obtained from in cell dose response experiments in EmCit_MCF7 cells (D)). Correspondig molecular RPTPγ/EGFR-ratio (see G, H, Fig EV2H) is depicted above the graphs; Inserted into each graph are the values of Hill coefficient (HC) and EC50 of the fitted hill equation (95% confidence interval). 2nd graph: Same as left graph with αp plotted vs αL both obtained from in cell dose response experiments in EmCit_MCF7 cells. 3rd-5th graph: Same as 2nd graph for EmCit_MCF7 RPTPγ-KO with RPTPγ-mTFP ectopic expression clustered by RPTPγ/EGFR-expression ratio and HC (Fig EV2G).",
    "ncbi_link": "mCit: 
mTFP: 
RPTPγ: 
RPTPγ: 5793"
  },
  {
    "caption": "G. Number of molecules obtained by normalizing background-subtracted fluorescence intensities of individual transfected cells against the mean background intensity of untransfected cells, yielding relative expressions levels independent on the fluorophore (methods). This value was then set into proportion to the known mean number of EGFR per MCF10A cell to yield absolute molecule count/cell. 1st column: EGFR-mCitrine in EmCit_MCF7 cells (N=3 biological replicates, n=102 cells); 2nd column EGFR-mCitrine expressed in EmCit_MCF7 RPTPγ-KO expressing RPTPγ-mTFP (N=3 biological replicates, n=26 cells); 3rd column: RPTPγ-mCitrine in MCF7 cells expressing additionally EGFR-mCherry (N=3 biological replicates, n=253 cells); 4th column: RPTPγ-mTFP expressed in EmCit_MCF7 RPTPγ-KO (N=3 biological replicates, n=26 cells) (individual cells with mean+SD). Color code in 2nd and 4th column is attribution to respective cluster (H and EV2G).",
    "ncbi_link": "mCherry: 
mCit: 
mCitrine: 
mTFP: 
RPTPγ: 
EGFR: 1956
RPTPγ: 5793"
  },
  {
    "caption": "C-E (C) in cell EGF-dose response imaging for RPTPγ-mCitrine oxidation. Left panel: Representative confocal micrographs of RPTPγ-mCitrine in EmTFP_MCF7 cells (top row) together with its oxidized fraction estimated using DyTo-FLIM (αox, bottom row), upon 10' stimulation with EGF-Alexa647 (0-160 ng/ml) including 5' together with 0.5 mM DyTo. Scale bar: 10 μm. Right panel: Quantification depicting the PM-proximal (orange) and PM-distal (blue) oxidized fractions as functions of receptor occupancy (αL) and corresponding EGF-Alexa647, or H2O2 concentration in EmTFP MCF7 cells expressing RPTPγ-mCitrine (WT) or RPTPγC1060S-mCitrine (C1060S) as well as WT cells treated with 0.5 mM atto590 instead of DyTo (atto590). Mean of individual cells (symbols) with mean±SD (black lines), N=3 biological replicates, n=13-15 cells per EGF dose. P: unpaired two-tailed t-test, between PM (serpentine peripheral structures) and endosomal (vesicular structures) fractions. (D) Same as in (C), for RPTPγ-mCitrine oxidation in p22phox-KO cells. N=3 biological replicates, n=14-26 cells per EGF dose. (E) Same as in (C), for TCPTP-mCitrine or TCPTPC216S-mCitrine (C216S) oxidation in EmTFP_MCF7 cells. N=3 biological replicates, n=18-21 cells per EGF dose. ",
    "ncbi_link": "mCitrine: 
mTFP: 
RPTPγ: 
TCPTP: 
p22phox: 1535"
  },
  {
    "caption": "B. Fraction of RPTPγ-mCitrine (cyan) or EGFR-mCherry (green) that spatially overlaps with Rab11a (top left, N=3, n=23-26 cells per timepoint), PM (bottom left, N=3 biological replicates, n=15-17 cells), EEA1-positive early endosomes (top right, N=3 biological replicates, n=25-28 cells) or Rab7-positive late endosomes (bottom right, N=3 biological replicates, n=23-27 cells) in MCF7 cells as function of time after 160 ng/ml EGF-stimulus. Orange symbols/dotted line: same for EGFR-mCitrine in RPTPγ-KO cells (N=3 biological replicates, n=17-21 cells). P: unpaired two-tailed t-test; colored P values compare to the respective species before stimulation, black in between species.",
    "ncbi_link": "RPTPγ: 5793"
  },
  {
    "caption": "C. Left: Representative confocal micrographs of MCF7 cells depicting the steady state localization of expressed RPTPγ-mCitrine (cyan), without (top) or with co-expression of BFP-Rab11a (yellow, bottom). Top right: Quantification of PM-localized fraction of RPTPγ-mCitrine without (WT) and with co-expression of BFP-Rab11a. Bottom right: Fraction of RPTPγ-mCitrine localized to the PM in individual cells as a function of BFP-Rab11a expression level, measured by mean BFP-fluorescence intensity. Scale bar: 10 μm. N=2 biological replicates, n>40 per condition, mean±SD,; P: unpaired two-tailed t-test.",
    "ncbi_link": "BFP: 
Rab11a: 8766"
  },
  {
    "caption": "F. Left: Representative IP-western blot showing co-IP of EGFR (2nd row) upon RPTPγ-mCitrine (1st row: lanes 1-6) or RPTPγC1060S-mCitrine (lane 7) pull-down by anti-GFP antibody from lysates of MCF7 cells co-transfected with EGFR and RPTPγ-mCitrine or RPTPγC1060S-mCitrine: without stimulus (0 ng/ml), upon 10' stimulus with EGF-Alexa647 (5-320 ng/ml, also displayed as corresponding receptor-occupancy αL, Fig 2D) or 8 mM of H2O2. 3rd and 4th row: total protein concentrations of RPTPγ-mCitrine and EGFR in the lysate measured by western blot as input control for the Co-IP. Right: corresponding ratiometric quantification of co-immunoprecipitated EGFR over pulled down RPTPg-mCitrine or RPTPγC1060S-mCitrine protein bands (mean±SD, N=4 biological replicates, P: unpaired two-tailed t-test)",
    "ncbi_link": "mCitrine: 
RPTPγ: 
EGFR: 1956"
  },
  {
    "caption": ". F. Change of the free parameter groups Γ1 = γ1RPTPγ/EGFRT and Β = β EGFRT/k1 in EmCit_MCF7 RPTPγ-KO (blue), EmCit_MCF7 (red), EmCit_MCF7 RPTPγ-KO expressing RPTPγ-mTFP splitted in 3 clusters with increasing RPTPγ−mTFP/EGFR-mCitrine ratio (yellow, green, purple; Fig 2H, EV2G) and WT MCF7 cells (black",
    "ncbi_link": "mCit: 
mCitrine: 
mTFP: 
RPTPγ: 
EGFR: 1956
RPTPγ: 5793"
  },
  {
    "caption": "C. Top: Representative Western blot against Erk and phosphorylated Erk (pT202 and pY204) in WT (red) compared to p22phox-KO (green) MCF7 cells after the indicated times of sustained stimulation with 20 ng/ml EGF-Alexa647. Bottom: Corresponding quantification of the fraction of phosphorylated ERK as a function of stimulation time. Mean±SD, N=4 biological replicates, P: unpaired two-tailed t-test.",
    "ncbi_link": "p22phox: 1535"
  },
  {
    "caption": "D. Quantification of cell proliferation using retinoblastoma (Rb) protein phosphorylation detected by immunofluorescence, for WT (red), RPTPγ-KO (blue) and p22phox-KO (green) MCF7 cells without or post 24 h of EGF-Alexa647 treatment (1, 20, 160 ng/ml). Mean±SEM, N=3 biological replicates, n>2000 cells per EGF stimulus per cell line, P: two-way ANOVA with Tukey multiple comparisons.",
    "ncbi_link": "p22phox: 1535
RPTPγ: 5793"
  },
  {
    "caption": "E. Quantification of the culture-well area (%) occupied by proliferating cell-colonies, obtained from clonogenic assays of WT, RPTPγ-KO and p22phox-KO MCF7 cells, plated either in medium containing 20 ng/ml EGF and 0.5% FCS (left: orange bars, N=3-4 biological replicates, 11-12 wells each) or complete serum growth medium containing 10% FCS (right: pink bars, N=4 biological replicates, 12 wells each). Mean±SEM, P: unpaired two-tailed t-test with Welch's correction.",
    "ncbi_link": "p22phox: 1535
RPTPγ: 5793"
  },
  {
    "caption": "Alveolar macrophages from different donors were purified from BAL fluid by allowing them to attach to the culture dish for 2 hours. Subsequently, they were pre-treated overnight with either type I or type III IFNs (1 ng/mL IFN-λ1 and 10 U/mL IFN-α2, respectively) before infection with Sendai virus (SeV) and influenza A virus (IAV, strain PR8) for 6 hours as indicated. Total RNA was harvested and subjected to qPCR for quantification of the IFN response measured by IFNA2, IFNB1, and IFNL1. ISG response measured by ISG15 and RSAD2. Each colour corresponds to a donor; 9 different donors were analysed. The dashed line represents the detection limit. An ordinary one-way-ANOVA test was used for the statistical analysis: ns, not significant; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.",
    "ncbi_link": "IFNA2: 3440
IFNB1: 3456
IFNL1: 282618
ISG15: 9636
RSAD2: 91543"
  },
  {
    "caption": "Alveolar macrophages from different donors were purified from BAL fluid and pre-treated with either Poly(I:C) or IFN-λ1 (+; 1 ng/mL, or ++; 10 ng/mL) before infection with SARS-CoV-2. (A) Total RNA was harvested and subjected to qPCR for quantification of the IFN response measured by IFNA2, IFNB1, and IFNL1 (Donors marked in orange and blue were not quantifiable in all test conditions). (B) ISG response measured by ISG15, RSAD2, and IFIT1.",
    "ncbi_link": "IFIT1: 3434
IFNA2: 3440
IFNB1: 3456
IFNL1: 282618
ISG15: 9636
RSAD2: 91543"
  },
  {
    "caption": "Alveolar macrophages from different donors were purified from BAL fluid and infected with SARS-CoV-2 before treatment with either Poly(I:C) or IFN-λ1 (1 ng/mL). (B) Total RNA was harvested and subjected to qPCR for quantification of the IFN response measured by IFNA2, IFNB1, and IFNL1. (C) ISG response measured by ISG15, RSAD2, and IFIT1 (Donors marked in green and red were not quantifiable in all test conditions).",
    "ncbi_link": "IFIT1: 3434
IFNA2: 3440
IFNB1: 3456
IFNL1: 282618
ISG15: 9636
RSAD2: 91543"
  },
  {
    "caption": "(A) Total RNA was harvested from AMs and primary human airway epithelial cells (HAE) and subjected to qPCR for quantification of the ACE2 receptor. Each colour corresponds to a donor. The dashed line represents the detection limit.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(B) The presence of nucleoprotein mRNA of SARS-CoV-2 in AMs and primary HAE was also quantified after SARS-CoV-2 treatment. Each colour corresponds to a donor. An unpaired t-test test was used for statistical analysis: ****, P≤0.0001.",
    "ncbi_link": "nucleoprotein: 43740575"
  },
  {
    "caption": "A,B, Immunostaining for CD31+ blood vessels in control (ctrl, A) and Gpr124KO (B) forebrains. Note the normal vasculature in the cortical hem (asterisk) of Gpr124KO mice.",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "C,D, Immunostaining for Pax6 in control (C) and Gpr124KO (D) forebrains to reveal the lateral extension of the neocortex (dashed line) between the cortical hem (arrowhead) and the lateral ganglionic eminence (arrow). E, Quantification of the lateral extension of the cortex in control and Gpr124KO brains (mean±SEM; N=10; *** p<0.001).",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "F,G Staining for EdU (red) and Ki67 (green) in control (F) and Gpr124KO (G) cortices at E13.5, 24 hours after EdU injection. H, Quantification of Ki67+ NPCs in the VZ (blue), SVZ/CP (grey) and of Ki67- neurons (cyan) generated from EdU-labeled NPCs in control and Gpr124KO embryos (mean±SEM; N=4 (control) and N=3 (Gpr124KO); * p<0.05, ** p<0.01). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "I,J, Immunostaining for Tbr2 (red) and Pax6 (green ) in control (I) and Gpr124KO (J) cortices. K, Quantification of newborn BPs in the VZ of control and Gpr124KO cortices (mean±SEM; N=4; * p<0.05). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "L,M, Immunostaining for Tbr2 (red) and Ngn1 (green) in control (L) and Gpr124KO (M) cortices. N,O Quantification of neurogenic (Ngn1+) RGs and BPs (N) or expanding (Tbr2- Ngn1-) RGs (O) in control and Gpr124KO cortices (mean±SEM; N=4; * p<0.05, *** p<0.001). Note that the fraction of total BPs is significantly reduced (Fig 1K) while the fraction of Ngn1+BPs is insignificantly reduced (Fig 1N), because the proportion of Ngn1+Tbr2+ cells within all BPs is slightly, though statisically insignificantly higher in the Gpr124KObrains (see Fig S2M). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "P,Q Stainings for Tbr2 (red) and for Tis21-GFP expression (green) in control (P) and Gpr124KO (Q) cortices. R,S Quantification of neurogenic (Tis21-GFP+) RGs and BPs (R) or expanding (Tbr2- Tis21-GFP-) RGs (S) in control and Gpr124KO cortices (mean±SEM; N=4; *** p<0.001). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "A,B, Staining for Isolectin B4+ blood vessels in control (A) and Gpr124ECcKO (B) forebrains. Asterisks mark the lateral ventricles.",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "C,D, Staining for pimonidazole (PIMO, green) and Isolectin B4+ blood vessels (red) in ctrl (C) and Gpr124ECcKO (D) cortices.",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "E,F, Immunostaining for Pax6 in control (E) and Gpr124ECcKO (F) forebrain sections to reveal the lateral extension of the neocortex (dashed line) between the cortical hem (arrowhead) and the lateral ganglionic eminence (arrow). G, Quantification the lateral extension of the cortex in control and Gpr124ECcKObrains (mean±SEM; N=6 for ctrl and N=8 for Gpr124ECcKO; * p<0.05).",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "H,I, Staining for EdU (red) and Ki67 (green) in control (H) and Gpr124ECcKO (I) cortices at E13.5, 24 hours after EdU injection. J, Quantification of Ki67+ NPCs in the in VZ (blue), SVZ/CP (grey) and of Ki67- neurons (cyan) generated from EdU-labeled NPCs in control and Gpr124ECcKO embryos (mean±SEM; N=4; * p<0.05, ** P<0.01). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "K,L, Immunostaining for Tbr2 (red) and Ngn1 (green) in control (K) and Gpr124KO (L) cortices. M-O, Quantification of neurogenic (Ngn1+) RGs and BPs (M), newborn BPs (N) or expanding (Tbr2- Ngn1-) RGs (O) in control and Gpr124ECcKO cortices (mean±SEM; N=4; * p<0.05, ** p<0.01). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "A, qRT-PCR analysis of NSC-specific markers (Fabp7, Hes5) and neuronal markers (Dcx, Tubb3) in the Prom1+ fraction, presented as fold change compared to the Prom1- fraction) from WT cortices at E14.5 (mean±SEM; N=3 for Dcx; N=6 for all other genes).",
    "ncbi_link": "Dcx: 13193
Fabp7: 12140
Hes5: 15208
Prom1: 19126
Tubb3: 22152"
  },
  {
    "caption": "F, Western blot for HIF-1 (top), HIF-2 (middle) and a-tubulin as loading control (bottom) using forebrain lysates from E13.5 control (left) or Gpr124KOembryos (middle). HIF-1/2-transfected HEK293 cells served as positive control (right). G, Quantification of HIF-1 band intensities shown in panel F (mean±SEM; N=3; ** p<0.01).",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "H,I, Immunostaining for HIF-1α (red) and DAPI (blue) in control (H, H', H'') and Gpr124KO (I,I',I'') cortices. Panels H',H'',I' and I'' are magnifications of the boxed areas in panels I and J, showing HIF-1α signal alone (H',I') or together with DAPI (H'',I''). Asterisks indicate autofluorescent blood cells. The dashed line indicates the basal boundary of the VZ. Scale bar = 100 µm. Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "J, qRT-PCR analysis of HIF-1 target gene expression in VZ cells from the cortex of control and Gpr124KO E13.5 embryos (mean±SEM; N=4; *** p<0.001). SVZ, subventricular zone; VZ, ventricular zone.",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "A, qRT-PCR analysis of HIF-1 and HIF-1 target gene expression in cortices from E13.5 WT and HIF-1αCC+/-embryos (mean±SEM; N=8 for WT and N=5 for HIF-1αCC+/-; * p<0.05, ** p<0.01, *** p<0.001).",
    "ncbi_link": "HIF-1: 15251
HIF-1α: 15251"
  },
  {
    "caption": "B,C, Staining for EdU (red) and Ki67 (green) in WT (B) and HIF-1αCC+/- (C) cortices at E13.5, 24 hours after EdU injection. D, Quantification of Ki67+NPCs in the in VZ (blue), SVZ/CP (grey) and of Ki67-neurons (cyan) generated from EdU-labeled NPCs in control and HIF-1αCC+/-brains (mean±SEM; N=4; * p<0.05). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "HIF-1α: 15251"
  },
  {
    "caption": "E,F, Immunostaining for Tbr2 (red) and Ngn1 (green) in WT (E) or HIF-1αCC+/- (F) cortices at E13.5. G-I Quantification of neurogenic (Ngn1+) RGs and BPs (G), newborn BPs (H) or expanding (Tbr2-Ngn1-) RGs (I) in control and HIF-1αCC+/-cortices at E13.5 (mean±SEM; N=5; * p<0.05, ** p<0.01, *** p<0.001). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "HIF-1α: 15251"
  },
  {
    "caption": "J, Whole mount image of brains from WT or HIF-1αCC+/-mice at P5. K Quantification of cortex area in brain sections from P5 WT or HIF-1αCC+/-mice (mean±SEM; N=8 (WT) or N=6 (HIF-1αCC+/-); * p<0.05).",
    "ncbi_link": "HIF-1α: 15251"
  },
  {
    "caption": "L,M, Staining with Hoechst 33248 in P5 WT (L) or HIF-1αCC+/- (M) cortices. N, Quantification of cortical thickness of WT and HIF-1αCC+/-cortices. The double arrow denotes the measured thickness of the cortex. N, Quantification of cortical thickness of WT and HIF-1αCC+/-cortices (mean±SEM; N=8 (WT) or N=6 (HIF-1αCC+/-); *** p<0.001).",
    "ncbi_link": "HIF-1α: 15251"
  },
  {
    "caption": "O-Q, Epifluorescent images of the E16.5 cortex, 3 days after in utero electroporation (IUE) with EGFP alone (ctrl, O), wild type HIF-1+EGFP (P) or mutant HIF-1ΔC+EGFP (Q). O',P' and Q' are magnifications of the boxed area in their respective original panel. R, Quantification of EGFP+ cells in the cortical zones VZ/SVZ, IZ and CP shown in O-Q (mean±SEM; N=5; ** p< 0.01,* p<0.05). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "HIF-1: 15251"
  },
  {
    "caption": "B-E, Staining for pimonodazole (PIMO, green) and Isolectin B4 (IB4,red) in Gpr124KO (B,C) and control (D,E) cortices after exposure of the pregnant dams to 21% O2 (B,D) or 80% O2 (C,E). Compared to the pimonidazole staining in panels B,C, the intensity of this staining is much weaker in panels D,E. For reasons of clarity, the pimonidazole staining in panels D,E was therefore enhanced, equally in both panels.",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "F,G, Immunostaining for HIF-1 (red) and DAPI (blue) in Gpr124KOcortices after exposure of the pregnant dams to 21% O2 (F) or 80% O2 (G). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "H,I, Immunostaining for Tbr2 (red) and Ngn1 (green) in Gpr124KO cortices after exposure of the pregnant dams to 21% O2 (H) or 80% O2 (I). J-L Quantification of neurogenic (Ngn1+) RGs and BPs (J), newborn BPs (K) or expanding (Tbr2- Ngn1-) RGs (L) in Gpr124KO cortices after exposure of the pregnant dams to 21% O2 or 80% O2 (mean±SEM; N=4 for 21% O2 and N=5 for 80% O2; * p<0.05, ** p<0.01). M,N, Immunostaining for Tbr2 (red) and Ngn1 (green) in control cortices after exposure of the pregnant dams to 21% O2 (M) or 80% O2 (N). O-Q Quantification of neurogenic (Ngn1+) RGs and BPs (O), newborn BPs (P) or expanding (Tbr2-Ngn1-) RGs (Q) in control cortices after exposure of the pregnant dams to 21% O2 or 80% O2 (mean±SEM; N=5; ** p<0.01). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "Gpr124: 78560"
  },
  {
    "caption": "A, qRT-PCR analysis of glycolytic enzymes in Prom1+ VZ cells and their Prom1- differentiated progeny (BPs and neurons) in WT cortices at E14.5 (mean±SEM; N=3 (Hk2, Gapdh); N=6 (Eno1; Ldha; ** p<0.01).",
    "ncbi_link": "Eno1: 13806
Gapdh: 14433
Hk2: 15277
Ldha: 16828
Prom1: 19126"
  },
  {
    "caption": "C, qRT-PCR analysis of Pfkfb3 expression in proliferating NSCs, transduced with scr or Pfkfb3shRNA#1 (mean±SEM; N=4; * p<0.05).",
    "ncbi_link": "Pfkfb3: 170768"
  },
  {
    "caption": "D, Measurement of lactate secretion from proliferating NSCs transduced with scr or Pfkfb3shRNA#1, normalized to cellular protein content (mean±SEM; N=3; * p<0.05).",
    "ncbi_link": "Pfkfb3: 170768"
  },
  {
    "caption": "E, Measurement of mitochondrial respiration rate (oxygen consumption rate, OCRMITO; see supplemental methods) in proliferating NSCs, transduced with scr or Pfkfb3shRNA#1, normalized to cellular protein content (mean±SEM; N=3; N.S., not significant).",
    "ncbi_link": "Pfkfb3: 170768"
  },
  {
    "caption": "F-H, Epifluorescent images of the E15.5 cortex, 3 days after in utero electroporation (IUE) with EGFP + scr shRNA (F), EGFP + Pfkfb3 shRNA#1 (G) or EGFP + Pfkfb3 shRNA#2 (H). J, Quantification of EGFP+ cells in the cortical zones VZ/SVZ, IZ and CP shown in panels F-H (mean±SEM; N=4 for scr and N=5 for Pfkfb3 shRNAs; * p<0.05, ** p< 0.01, *** p< 0.001). K-M, Epifluorescent images of the mouse cortex after in utero electroporation (IUE) with HIF-1α and scr shRNA (K) or with HIF-1α and two different Pfkfb3 shRNAs (L,M) at E16.5, 3 days after transfection. N, Quantification of EGFP+ cells in the cortical zones VZ/SVZ, IZ and CP shown in K-M (mean±SEM; N=5; * p<0.05, ** p< 0.01, *** p< 0.001). Full, dotted and dashed lines indicate basal and apical boundaries of the cortex or boundaries of the cortical zones, respectively. CP, cortical plate; IZ, intermediate zone; SVZ, subventricular zone; VZ, ventricular zone. Scale bar: 100 µm",
    "ncbi_link": "HIF-1α: 15251
Pfkfb3: 170768"
  },
  {
    "caption": "Indicated cell lines were treated as depicted in Figure 2. Data are depicted as mean +/- standard deviation of three independent biological experiments. Statistical significance was determine by two-tailed Student"s t test where *=p<0.05, **=p<0.01,***=p<0.001, ****=p<0.0001. LNCaP: E2F1, p=0.0159; PCNA, p=0.0217; MCM7, p=4.0936e-6; CCNA2, p=0.0005. C4-2: E2F1, p=0.0074; PCNA, p=0.1258; MCM7, p=3.7471e-5; CCNA2, p=0",
    "ncbi_link": "CCNA2: 890
E2F1: 1869
MCM7: 4176
PCNA: 5111"
  },
  {
    "caption": "Left: Data generated as described above in Figure 2 was used to generate a heatmap of homologous recombination (HR) gene expression after the indicated treatment regimens. Middle: Selected GSEA MSigDB Oncogenic Signature pathways are shown. Right: Data generated as described above in Figure 2 was compared to a previously described HR deficiency transcriptional profile (Peng et al., Nature Communications, 2014). This profile was derived by independently silencing either BRCA1, RAD51, or BRIP1, followed by transcriptional analyses. The union of these three data sets was used to generate the signature. Cut-offs for comparison were a p value<0.05, and fold change of 1.5. Venn diagrams show the overlapping and non-overlapping genes of both down- (top) and up-regulated (bottom) genes in the previously-defined HR deficiency signature, and the PARPi-responsive transcriptome",
    "ncbi_link": "BRCA1: 672
BRIP1: 83990
RAD51: 5888"
  },
  {
    "caption": "C4-2 cells were treated as depicted in Figure 2. ChIP was performed using the indicated antisera, and the subsequent DNA was isolated and used in qPCR reaction using primers designed to amplify the indicated genomic loci: BRCA2 enhancer, RAD51 promoter, or TOP3A promoter",
    "ncbi_link": "BRCA2: 675
RAD51: 5888
TOP3A: 7156"
  },
  {
    "caption": "Indicated cell lines were transfected with indicated constructs, and treated with veliparib. Cell growt was assessed LNCaP cell growth: Control transfection, p=0.0220; BRCA1 transfection, p=0.67787; BRCA2 transfection, p=0.4676. C4-2 cell growth: Control transfection, p=0.0354; BRCA1 transfection, p=0.1638; BRCA2 transfection, p=0.2519. 22Rv1 cell growth: Control transfection, p=0.0039; BRCA1 transfection, p=0.1085; BRCA2 transfection, p=0.2781",
    "ncbi_link": "BRCA1: 672
BRCA2: 675"
  },
  {
    "caption": "Indicated cell lines were transfected with indicated constructs, and treated with veliparib DDR via γH2AX was assessed LNCaP γH2AX: Control transfection, p=0.0008; BRCA1 transfection, p=0.9035; BRCA2 transfection, p=0.4685. C4-2 γH2AX: Control transfection, p=0.0009; BRCA1 transfection, p=0.6362; BRCA2 transfection, p=0.4217. 22Rv1 γH2AX: Control transfection, p<0.0001; BRCA1 transfection, p=0.4698; BRCA2 transfection, p=0.4937",
    "ncbi_link": "BRCA1: 672
BRCA2: 675"
  },
  {
    "caption": "G. mRNA levels of CTGF measured by real-time PCR in IGR37 treated with DMSO or NB-360 (T-test analysis, * = p-value<0.05, N=3 biological replicates, data are mean ±SD).",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "H. CTGF mRNA level measured by real-time PCR in IGR39 treated with IGR39 conditioned medium (CTRL) or with IGR37 conditioned medium (CM), N=4 biological replicates. T-test analysis, *** p-value <0.001, data are mean ±SD.",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "I. CTGF mRNA level measured by real-time PCR in IGR39 supplemented with recombinant PMEL amyloid fibrils (0.5µM), N=3 biological replicates. T-test analysis: *** p-value <0.001, data are mean ±SD.",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "J. CTGF mRNA level measured by real-time PCR in IGR37 treated with DMSO, NB-360 or NB-360 plus recombinant PMEL amyloid fibrils (0.5µM), N=3 biological replicates. T-test analysis* = p-value<0.05, ** = p-value<0.01. Data are mean ±SD.",
    "ncbi_link": "CTGF: 1490"
  },
  {
    "caption": "(a) PPARγ mRNA expression in sperm from control and MSUS mice. Control n = 15, MSUS n = 13, two-tailed Student's t-test, P = 0.029, t = 2.30, df = 26.",
    "ncbi_link": "PPARγ: 19016"
  },
  {
    "caption": "B Mass spectrometry analysis of proteins co-purified with Ccq1HA. Shown is a volcano plot for proteins significantly enriched in Ccq1HA relative to untagged Ccq1 (left panel: WT cells; right panel: rik1∆ cells). Members of the CLRC complex and shelterin are highlighted in red and blue, respectively. Bottom panel displays proteins enriched (log2 ≥ 5 or pval ≤ 0.01)",
    "ncbi_link": "rik1: 2539050"
  },
  {
    "caption": "A Left: Schemes of CLRC and the shelterin complex. Middle and right: Scheme depicting the position of the ura4+ reporter gene and heterochromatin islands relative to telomeric repeats and TAS regions; note that the minichromosomesome Ch16 does not contain TAS. B-C ChIP-qPCR analyses of H3K9me2 (B) and H3 (C) in WT and ccq1Δ cells (n = 3 independent experiments. D Fold change of WT over ccq1Δ for H3K9me2 and H3 level Data information: In (B, C), data are normalized to input and to the average of three euchromatic loci (EC) as internal contro and represented as mean ± SEM",
    "ncbi_link": "ccq1: 2539352"
  },
  {
    "caption": "A ChIP-qPCR analysis of H3 at endogenous TAS and a fragment spanning the TAS region from 115-905 bp (relative to telomeric repeat) inserted into the leu1+ locus (see scheme). The TAS fragment was inserted into a strain that lacks endogenous TA Shown are ChIP analyses for WT (left) and ccq1∆ (right; note different the scale of the y-axis) (n = 9-10 independent experiments except for ectopic TAS in ccq1∆ strain where n = 3) Data information data are represented as mean ± SE",
    "ncbi_link": "ccq1: 2539352"
  },
  {
    "caption": "B ChIP-qPCR analysis of H3 at reporter genes (ura4+ and his3+) at various chromosomal locations (see schemes) in WT cells. TAS1, TAS2, and TAS3 correspond to position 116 bp, 2851 bp and 6291 bp (relative to telomeric repeats), respectively (n = 3 independent experiments). Data information data are represented as mean ± SE",
    "ncbi_link": "his3: 
ura4: "
  },
  {
    "caption": "A, B RT-qPCR analysis of transcript levels of TERRA (A) and tlh1+ (B) in WT strain and mutants as indicated (double mutants with ccq1Δ are indicated by blue dot). Data information: In (A, B), data is represented as mean ± SEM from 3 independent experiments and shown relative to WT leve",
    "ncbi_link": "ccq1: 2539352
tlh1: 2541932"
  },
  {
    "caption": "A Genomic copy number of his3+, ura4+ and TAS1 in indicated strains harboring the reporter genes tel1L::his3+ and tel2L::ura4+. Cultures from individual WT and freshly generated knockout clones (ccq1Δ, n = 16; clr4Δ, n = 5; ccq1Δ clr4Δ, n = 5) were pre-grown on selective media for several days and inoculated at day 0 to grow in liquid media with regular back-dilution (every 24 hours, approximately 7 generations). Samples were taken at indicated harvest times, and relative copy numbers of genomic regions were assessed by qPCR (normalization against intrachromosomal loci). Black and rainbow color lines indicate WT strains and individual ccq1+ deletion mutants (clones), respectively",
    "ncbi_link": "his3: 
ura4: 
ccq1: 2539352
clr4: 2540825"
  },
  {
    "caption": "B qPCR analysis as in (A) but with strains harboring the minichromosome Ch16 m23::ura4+ (ccq1Δ, n = 14). Since Ch16 is unstable in ccq1Δ cell Note that Ch16 does not harbor TAS sequences",
    "ncbi_link": "ura4: 
ccq1: 2539352"
  },
  {
    "caption": "A. Representative pictures of immunostaining for F4/80 (green) in Control and CriptoMy-LOF TA sections at day 2 (top panel) and 5 (bottom panel) after injury. B. Quantification of F4/80 staining/damaged area (μm2) at day 2 (top graph) and 5 (bottom graph) after injury. Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 50 μm. Magnification of the boxes is 3.5 x. Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n≥5 biological replicates; **P<0.01, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "C. Representative pictures of immunostaining for CD206 in Control and CriptoMy-LOF TA sections at day 2 (top panel) and 5 (bottom panel) after injury, respectively. D-E. Quantification of CD206+ MPs per area (mm2) at day 2 (D) and 5 (E) after injury. Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 50 μm. Magnification of the boxes is 3.5 x. Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n≥5 biological replicates; **P<0.01, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "A. Representative flow cytometry dot plots showing the percentage of GFP+ cell population in GFP-Control and GFP-CriptoMy-LOF muscles at day 2 (top panel) and 5 (bottom panel) after injury. Percentage of GFP+ cells expressing F4/80 in GFP-Control and GFP-CriptoMy-LOF muscles is shown at day 2 after injury (middle panel). Data are mean±SEM (n=4 biological replicates; P=ns; Student's t-test).",
    "ncbi_link": "GFP: 
Cripto: 21667"
  },
  {
    "caption": "B. qRT-PCR analysis of pro- (Nos2, Mcp1 and Tnfα) and anti- (Arg1, Fizz1, Il10, Il4rα and Tgfβ) inflammatory markers in GFP-CriptoMy-LOF and GFP-Control MPs at day 2 and 5 after injury. Data represent mean±SEM of relative mRNA level normalized with Gapdh (n≥4 biological replicates; ***P<0.001, Student's t-test).",
    "ncbi_link": "GFP: 
Arg1: 11846
Mcp1: 20296
Gapdh: 14433
Il10: 16153
Il4rα: 16190
Nos2: 18126
Fizz1: 57262
Cripto: 21667
Tgfβ: 21803
Tnfα: 21926"
  },
  {
    "caption": "C. Representative pictures of immunostaining for GFP (green), CD206 (red), pSMAD3 (white) in GFP-Control and GFP-CriptoMy-LOF TA sections at day 5 after injury. Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x. D. Quantification of GFP+/CD206±/pSMAD3± cell distribution in TA sections from GFP-Control and GFP-CriptoMy-LOF at day 5 after injury. Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Data are mean±SEM (n=5 biological replicates; **P<0.01, Student's t-test). ",
    "ncbi_link": "GFP: 
Cripto: 21667"
  },
  {
    "caption": "E. Representative flow cytometry dot plots of F4/80+/Ly6CLow cell population gated on GFP+ cells from GFP-Control and GFP-CriptoMy-LOF muscles at day 5 after injury. Data are mean±SEM (n=3 biological replicates; P=ns; Student's t-test).",
    "ncbi_link": "GFP: 
Cripto: 21667"
  },
  {
    "caption": "(F) Smear plot of RNA-seq data from GFP+/F4/80+/Ly6CLow cells FACS sorted from GFP-Control and GFP-CriptoMy-LOF muscles at day 5 after injury. Data show the expression level as Log2 fold-change (FC) [Log2(GFP-Control/GFP-CriptoMy-LOF)], against Log2(expression) [Log2(average of gene expression across all samples], for each individual gene. The blue lines correspond to LogFC of 1 and -1. (n=3 biological replicates).",
    "ncbi_link": "GFP: 
Cripto: 21667"
  },
  {
    "caption": "C. Minimal Feret's diameter distribution of Control and CriptoMy-LOF myofibers at day 5 (top panel) and 30 (bottom panel) after CTX injection. Data are mean±SEM (n=5 biological replicates; P=ns, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "F. Minimal Feret's diameter distribution of Control and CriptoMy-LOF myofibers at day 5 (top panel) and 30 (bottom panel) after re-injury (CTX-II).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "B. Representative pictures of immunostaining of mdx-Control and mdx-CriptoMy-LOF diaphragm sections with GFP (green) and CD206 (white; left panel), pSMAD3 (red; middle panel) and GFP and pSMAD3 (right panel). C-E. Quantification of GFP (C), GFP/CD206 (D) and GFP/pSMAD3 (E) positive cells per area (mm2) in mdx-Control and mdx-CriptoMy-LOF diaphragms. Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n≥5 biological replicates; **P<0.01, Student's t-test). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "F-G. Representative pictures of Picrosirius red staining of mdx-Control and mdx-CriptoMy-LOF diaphragm sections (F) and quantification of picrosirius red staining (G). Data are expressed as percentage of stained area and are box plots displaying minimum, first quartile, median, third quartile and maximum (n=5 biological replicates; *P<0.05, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "H. Hydroxyproline (HOP) concentration in mdx-Control and mdx-CriptoMy-LOF diaphragm muscle sections. Data are expressed as HOP levels (μg) per muscle section volume (mm3) and as box plots displaying minimum, first quartile, median, third quartile and maximum (n=5 biological replicates; **P<0.01, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Representative images of Laminin (red) immunostaining of mdx-Control and mdx-CriptoMy-LOF diaphragm sections of centrally nucleated myofibers. Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Representative mdx-Control and mdx-CriptoMy-LOF diaphragm sections minimal Feret's diameter distribution of centrally nucleated myofibers. Data are expressed as mean±SEM (n=5 biological replicates; *P<0.05; ***P<0.001; Student's t-test)",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Representative mdx-Control and mdx-CriptoMy-LOF diaphragm sections minimal Feret's diameter distribution Variance coefficient of centrally nucleated myofibers. box plots displaying minimum, first quartile, median, third quartile and maximum",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "L-M. Representative images of eMHC (red) immunostaining of mdx-Control and mdx-CriptoMy-LOF diaphragm sections (L) and quantification of eMHC+ myofibers per area (mm2, M). Data are expressed as box plots displaying minimum, first quartile, median, third quartile and maximum (n=5 biological replicates; *P<0.05; Student's t-test). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "A. Representative pictures of CD31 (red) immunostaining of Control and CriptoMy-LOF TA sections at day 5 (left panel) and 30 (right panel) after single injury (CTX-I). B-D. Quantification of CD31+ capillary number per area (mm2; B), average of capillary cross-sectional area (µm2; C) and percentage of small (<20 µm2) and large (>100 µm2) capillaries (D) in Control and CriptoMy-LOF injured muscles at indicated time points after single injury (CTX-I). Data are mean±SEM (n=5 biological replicates; *P<0.05; **P<0.01; ***P<0.001, Student's t-test). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "E. Representative pictures of CD31 (red) immunostaining of Control and CriptoMy-LOF TA sections at day 5 (left panel) and 30 (right panel) after re-injury (CTX-II). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "F. Representative pictures of mdx-Control and mdx-CriptoMy-LOF diaphragm sections immunostained with VEcad (red). Data information: Nuclei were counterstained with DAPI (blue). Scale bar: 100 μm. Magnification of the boxes is 3.5 x.",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "G-H. Quantification of CD31+ capillary number per area (mm2; G) and average of capillary cross-sectional area (µm2; H) in Control and CriptoMy-LOF injured muscles at the indicated time points after re-injury (CTX-II) Data are mean±SEM (n=6 biological replicates; *P<0.05; ***P<0.001, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "I-J. Quantification of capillary number per area (mm2; I) and average of capillary cross-sectional area (µm2; J) in mdx-Control and mdx-CriptoMy-LOF diaphragm muscles. Data are mean±SEM (n=5 biological replicates; ***P<0.001, Student's t-test).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "A. Representative pictures of double immunostaining with VEcad (red; left and middle panel) and KLF4 (green, left panel) or TCF4 (green, middle panel), and with CD31 (red; right panels, confocal pictures) and TCF4 (white, right panel) on Control and CriptoMy-LOF TA sections at day 5 after injury. B-D. Quantification of VEcad/KLF4 (B), VEcad/TCF4 (C) and CD31/TCF4 (D) double positive cells per area (mm2) in Control and CriptoMy-LOF TA sections at day 5 after injury. Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "E. Representative Confocal pictures of CD31+ (red) and PDGFRα+ (green) immunostaining on Control and CriptoMy-LOF TA sections at day 5 after injury. F-G. Quantification of CD31+/PDGFRα+ (F) and CD31-/PDGFRα+ (G) cells per area (mm2). Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "H-I. Representative pictures of triple immunostaining with VEcad (red), KLF4 (green) and pSMAD3 (white) on Control and CriptoMy-LOF TA sections at day 5 after injury (H) and quantification of VEcad/KLF4/pSMAD3 triple positive cells per area (mm2; I). Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Representative pictures of double immunostaining with VEcad (red) and KLF4 (green) on Control and CriptoMy-LOF TA sections at day 5 after re-injury (CTX-II Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Representative pictures of double immunostaining with VEcad (red) and KLF4 (green) on diaphragm sections of mdx-Control and mdx-CriptoMy-LOF Data information: Nuclei were counterstained with DAPI (blue).",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Quantification of VEcad/KLF4 double positive cells per area (mm2) in Control and CriptoMy-LOF TA sections at day 5 after re-injury (CTX-II",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "Quantification of VEcad/KLF4 double positive cells per area (mm2) in diaphragm sections of mdx-Control and mdx-CriptoMy-LOF",
    "ncbi_link": "Cripto: 21667"
  },
  {
    "caption": "(C) miR-574-5p and miR-574-3p were highly expressed in the explanted failing hearts from chronic HF patients (n=17) versus donor non-failing hearts (n=6).",
    "ncbi_link": "miR-574-3p: 693159
miR-574-5p: 693159"
  },
  {
    "caption": "(D) miR-574-5p and miR-574-3p were induced in the hearts of mice with isoproterenol (ISO) infusion (4 weeks; n=10-12).",
    "ncbi_link": "miR-574-3p: 100124451
miR-574-5p: 100124451"
  },
  {
    "caption": "(E) miR-574-5p and miR-574-3p were induced in the hearts of mice under transverse aortic constriction (TAC) surgery (4 weeks; n=8-10).",
    "ncbi_link": "miR-574-3p: 100124451
miR-574-5p: 100124451"
  },
  {
    "caption": "(A) H&E of hearts from WT and miR-574-/- mice with or without isoproterenol (ISO) treatment for 4 weeks. Mice were between 8-10 weeks old females.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(B) Ratio of HW/TL (heart weight/tibia length) in WT and miR-574-/- mice (n=8/7/8/6 for 4 groups of WT, Veh.; WT, ISO; KO, Veh.; KO, ISO).",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(C) WGA (wheat germ agglutinin) staining in WT and miR-574-/- mice. Cross-sectional area (CSA) of CMs was measured and quantified (n≥500 cells). Scale bar: 50 μm. In the violin plot, black line shows median value for the group and peach dashed lines represent two quartile lines in each group.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(D) Picrosirius red staining in WT and miR-574-/- mice (n=6 per group). Scale bar: 1 mm.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(E) RT-qPCR of fetal cardiac genes in WT and miR-574-/- mice with ISO treatment (n=3 per group). ANF, atrial natriuretic factor; BNP, B-type natriuretic peptide; Myh6/Myh7, myosin heavy polypeptide 6/7; Col1a2/Col3a1, procollagen, type I, α2; type III, α1.",
    "ncbi_link": "Col1a2: 12843
procollagen, type I, α2: 12843
Col3a1: 12825
miR-574: 100124451
Myh6: 17888
myosin heavy polypeptide 6: 17888
Myh7: 140781
ANF: 230899
atrial natriuretic factor: 230899
B-type natriuretic peptide: 18158
BNP: 18158"
  },
  {
    "caption": "(F) TUNEL assay for heart tissue sections from WT and miR-574-/- mice under ISO versus vehicle treatment (n=6 per group). Scale bar: 10 μm.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(A) H&E staining of hearts from WT and miR-574-/- mice 4 weeks after transverse aortic constriction (TAC) surgery.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(B) Ratio of HW/TL in WT and miR-574-/- mice (n=8 per group).",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(C) WGA staining of hearts from WT and miR-574-/- mice 4 weeks after TAC surgery (n≥500 cells). Scale bar: 20 μm. In the violin plot, black line shows median value for the group and peach dashed lines represent two quartile lines in each group.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(D) Picrosirius red staining of hearts from WT and miR-574-/- mice under TAC surgery (n=8 per group). Scale bar: 1 mm.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(E) RT-qPCR of fetal cardiac genes in WT and miR-574-/- mice with TAC surgery (n=4 per group).",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(F) Echocardiography measurement of cardiac functions of hearts from WT and miR-574-/- mice 4 weeks post TAC (n=8 per group). FS, fractional shortening.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(A) Volcano curve analysis of dysregulated genes in miR-574-/- versus WT heart. The Padj is the P-values adjusted for multiple testing with correction using the Benjamini-Hochberg procedure. The dots above the dashed line show Padj<0.05.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(B) Heatmap of significantly upregulated genes in miR-574-/- mice at baseline analyzed by RNA-Seq. P60 male mice, n=3 per group, Padj<0.05. The Padj is the P-values adjusted for multiple testing with correction using the Benjamini-Hochberg procedure.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(E) Expression of Fam210a mRNA in the heart of miR-574-/- and WT mice from 3 biological replicates.",
    "ncbi_link": "Fam210a: 108654
miR-574: 100124451"
  },
  {
    "caption": "(F) Expression of FAM210A protein in the heart of miR-574-/- and WT mice. Protein intensity was quantified in the right panel (n=6 per group).",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(H) Dual luciferase reporter assays with co-transfection of miR-574-5p mimics and FLuc-Fam210a 3'UTR bearing wild type and mutant seed sequences. The assays were performed in three biological replicates.",
    "ncbi_link": "Fam210a: 108654
miR-574-5p: 100124451"
  },
  {
    "caption": "(I) Dual luciferase reporter assays with co-transfection of miR-574-3p mimics and FLuc-Fam210a 3'UTR bearing wild type and mutant seed sequences. The assays were performed in three biological replicates.",
    "ncbi_link": "Fam210a: 108654
miR-574-3p: 693159"
  },
  {
    "caption": "(B) The expression level of FAM210A mRNA in 15 human organs from the GTEx Portal database. TPM: transcripts per million of reads. The central band shows the median value and the box indicates the first and third quartiles. The sample size of human samples used for quantification in GTEx Portal database (from testis to pancreas): n=361/429/432/555/803/240/432/226/406/578/241/202/85/328/755.",
    "ncbi_link": "FAM210A: 125228"
  },
  {
    "caption": "(F,G) Protein expression of mitochondrial ETC component genes was measured in AC16 cells after following treatments in comparison with control cells: (F) siRNA knockdown of FAM210A. (G) FAM210A overexpression.",
    "ncbi_link": "FAM210A: 125228"
  },
  {
    "caption": "(A) miR-574-5p and miR-574-3p overexpression reduced FAM210A mRNA expression in AC16 cells (n=3 in each group). (B) miR-574-5p and miR-574-3p inhibition increased FAM210A mRNA expression in AC16 cells (n=3 in each group). ",
    "ncbi_link": "FAM210A: 125228
miR-574-3p: RF00929
miR-574-5p: 693159"
  },
  {
    "caption": "(C,D) Protein expression of mitochondrial ETC component genes was measured in AC16 cells after following treatments in comparison with control cells: (C) miR-574-5p or miR-574-3p overexpression. (D) Transfection of anti-miR-574-5p or anti-miR-574-3p inhibitor.",
    "ncbi_link": "miR-574-3p: RF00929
miR-574-5p: 693159"
  },
  {
    "caption": "(E,F) Mitochondrial membrane potential and ATP production in AC16 cells under ISO treatment (10 μM for 24 hr) with overexpression of miR-574-5p or miR-574-3p. >120 cells/group were quantified in (E) and n=4 biological replicates in (F). The dashed line in the violin plot shows medium value for the group and the dotted lines represent two quartile lines in each group.",
    "ncbi_link": "miR-574-3p: RF00929
miR-574-5p: 693159"
  },
  {
    "caption": "(G,H) Mitochondrial membrane potential and ATP production in primary mouse ACMs isolated from WT and miR-574-/- mice under ISO treatment. Scale bar: 10 μm. >110 cells/group were quantified in bottom panel of (G) and n=5 in (H).",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(I) transfection of miR-574-5p/3p in the absence or presence of FAM210A overexpression. All the Western blot images were provided as representative data from 3-4 biologically replicated experiments.",
    "ncbi_link": "FAM210A: 125228
miR-574-5p: 693159"
  },
  {
    "caption": "(J) Increased protein expression of FAM210A and ND1 in miR-574 KO hearts compared to WT hearts upon TAC surgery. N=5 hearts (~110-150 CM cells) were measured per group. The dashed line in the violin plot shows medium value for the group and the dotted lines represent two quartile lines in each group.",
    "ncbi_link": "miR-574: 100124451"
  },
  {
    "caption": "(H, I) Induction of Ctcflos and  Ucp1 in vivo during cold-induced iWAT browning. Relative expression levels  of (H) Ctcflos transcript 1 and (I) Ucp1 in iWAT  of C57BL/6J  mice held at 5°C for one week compared to age and weight matched mice held at 30°C  or 23°C, assessed by  quantitative PCR (qPCR). Mean and individual values, n=7 (biological replicates), one-way ANOVA (Šídák-test), **p< 0.01, ****p<0.0001.",
    "ncbi_link": "Ctcflos: 74161
Ucp1: 22227"
  },
  {
    "caption": "(D) Relative transcript levels of Ctcflos and Ucp1  in various tissues of 129S6 mice, assessed by  qPCR. Mean values ± SD, n=1 (biological replicate) for Ucp1n=3 (biological replicates) for Ctcflos .",
    "ncbi_link": "Ctcflos: 74161
Ucp1: 22227"
  },
  {
    "caption": "(E) Ctcflos, 45SrRNA and 12SrRNA transcript abundance in  nuclear, cytosolic and mitochondrial subfractions of primary  brite adipocytes of 129S6 mice, assessed by qPCR. Mean values ± SD, n=6 (biological replicates), two-way ANOVA (Tukey-test), ****p< 0.0001.",
    "ncbi_link": "Ctcflos: 74161"
  },
  {
    "caption": "(E) Relative Ucp1 transcript levels in response to Ctcflos tr1, 3 and 4 KD by ASO 1, 3, 4 and 2, 5 6, respectively, compared to nontargeting controls, assessed by  qPCR. Mean values ± SD, n=3-4 (biological replicates), one-way ANOVA (Šídák-test), ***p<0.001, ****p<0.0001.",
    "ncbi_link": "Ctcflos: 74161
Ucp1: 22227"
  },
  {
    "caption": "(F) Relative expression levels of cell death-inducing DNA fragmentation factor alpha-like effector A  (Cidea) and cytochrome c oxidase subunit 7a1 (Cox7a1) in Ctcflos tr1, 3 and 4 KD compared to control samples, assessed by qPCR. Mean values ± SD, n=3 (biological replicates)-4, unpaired t tests or in grey parenthesis two-way ANOVA (Šídák-test), n.s. p>0.05, *p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "cell death-inducing DNA fragmentation factor alpha-like effector A: 12683
Cidea: 12683
Cox7a1: 12865
cytochrome c oxidase subunit 7a1: 12865
Ctcflos: 74161"
  },
  {
    "caption": "(H)  Immunocytochemistry of UCP1 protein in response to Ctcflos tr1 KD by ASO 1 (UCP1 (red); DNA staining  by DAPI (green); phase contrast (PC) (gray)).",
    "ncbi_link": "Ctcflos: 74161"
  },
  {
    "caption": "Impact of Ctcflos KD on  mitochondrial  biogenesis. (R) Microscopic images of Mito Tracker stained brite adipocytes (Mito tracker (blue); DNA staining by DAPI (green);  phase contrast  (PC) (gray))",
    "ncbi_link": "Ctcflos: 74161"
  },
  {
    "caption": "(D) Relative  expression levels of  brite adipocyte marker genes uncoupling protein 1 (Ucp1), cell death-inducing DNA fragmentation factor alpha-like effector A (Cidea), cytochrome c oxidase subunit 7a1 (Cox7a1), peroxisome proliferator activated receptor γ coactivator 1α  (Pgc1a) and elongation of very long chain fatty acids-like 3 (Elovl3), comparing Ctcflos tr1 (ASO 1) and tr 3 and 4 (ASO 2) KD with their respective controls. Mean values ± SD, n=6 (biological replicates), unpaired t tests or in grey parenthesis two-way ANOVA (Šídák-test) n.s. p>0.05, **p<0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "cell death-inducing DNA fragmentation factor alpha-like effector A: 12683
Cidea: 12683
Cox7a1: 12865
cytochrome c oxidase subunit 7a1: 12865
Ctcflos: 74161
elongation of very long chain fatty acids-like 3: 12686
Elovl3: 12686
peroxisome proliferator activated receptor γ coactivator 1α: 19017
Pgc1a: 19017
Ucp1: 22227
uncoupling protein 1: 22227"
  },
  {
    "caption": "(K-M) Rescue of Ctcflos KD impact on Ucp1 gene transcription by Prdm16 overexpression. Primary iWAT cells infected with Prdm16- or turbo green fluorescent protein (GFP)-expressing viral particles at the second day of  proliferation, followed by reverse transfection at the first day of differentiation using nontargeting control (NC) or Ctcflos-targeting ASO1. Gene expression  analyzed 72 hours later by qPCR (K)  Transcript levels  of Ctcflos tr1 relative to Fabp4 (L) Transcript levels  of  Prdm16 relative to  Fabp4 (M)  Transcript levels of Ucp1  relative to Fabp4. Mean and individual values. Each graph presents pooled data from two experiments slightly varying virus titers. RM One-way ANOVA (Tukey-test), n.s. p>0.05, *p<0.05, **p<0.01, ***p<0.001. ",
    "ncbi_link": "GFP: 
green fluorescent protein: 
Ctcflos: 74161
Fabp4: 11770
Prdm16: 70673
Ucp1: 22227"
  },
  {
    "caption": "(B-D) Impact of splicing inhibition by different concentrations of general splicing inhibitor isoginkgetin on brite adipogenesis, (B) expressed as  Ucp1  relative to Fabp4 mRNA levels, (C) Ucp1 relative to  Gtf2b and (D) Fabp4  relative to Gtf2b. Mean values ± SD, n=3 (biological replicates), one-way ANOVA (Šídák-test), n.s. p>0.05, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "Fabp4: 11770
Gtf2b: 229906
Ucp1: 22227"
  },
  {
    "caption": "Effect of Ctcflos KD on  Serine/Arginine rich Splicing factor 2 (SC35/SRSF2) and nuclear speckle abundance in Ctcflos tr1 (ASO 1) KD and control cells (KD day 1 of differentiation, analysis after 48h). (E) Immunocytochemistry of SC35. SC35 signal (blue) alone (middle images) and SC35 (blue),  DNA staining by DAPI (green) and phase contrast (PC) (gray) combined (outer  images).",
    "ncbi_link": "Ctcflos: 74161"
  },
  {
    "caption": "Influence of Ctcflos  KD on Prdm16 alternative splicing. (O) Relative Prdm16  total, (P) Relative Prdm16 long  transcript levels 24 hours after Ctcflos  KD, comparing Ctcflos tr1 (ASO1) and tr3, 4 (ASO2) KD and control samples, assessed by  qPCR, Mean values ± SD, n=3-4 (biological replicates), unpaired t tests, n.s. p>0.05, * p<0.05, **p<0.01, ***p<0.001.",
    "ncbi_link": "Ctcflos: 74161
Prdm16: 70673"
  },
  {
    "caption": "Influence of Ctcflos  KD on  Prdm16 alternative splicing. (R, S) Fold change of Prdm16 short and Prdm16 long (R) ASO1 to NC and (S) ASO2 and NC 24 hours after Ctcflos KD, n=3-4 (biological replicates), unpaired t tests, n.s. p>0.05, ** p<0.01.",
    "ncbi_link": "Ctcflos: 74161
Prdm16: 70673"
  },
  {
    "caption": "(A) Neutralization assay of FD20 using SARS-CoV-2 pp harboring spike derived from four Variants of Concern as indicated. Mean ± s.d. are plotted (n = 3 biological replicates). Numbers in brackets indicate IC50 values in nM.",
    "ncbi_link": "spike: 43740568"
  },
  {
    "caption": "(C) Northern analysis of EVD RNA isoforms using a probe for the GAG region or for ACTIN2 (ACT2) as a loading control.",
    "ncbi_link": "GAG: 
ACT2: 821411
ACTIN2: 821411
EVD: 3770632"
  },
  {
    "caption": "(D) qPCR quantification of shGAG and flGAG-POL normalized to ACT2 and to GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE C SUBUNIT (GAPC) levels. qPCR was performed on n=3 biological replicates; bars: standard error. (**) = p-value < 0.01 (two-sided t-test between indicated values).",
    "ncbi_link": "shGAG: 
ACT2: 821411
flGAG-POL: 2745586
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE C SUBUNIT: 819567
GAPC: 819567"
  },
  {
    "caption": "(F-G) sRNA-seq profiles from EVD de-repressed in the ddm1 (F) or ddm1 dcl1 (G) backgrounds. Different siRNA size categories are stacked. Nomenclature as in (B).",
    "ncbi_link": "EVD: 3770632
ddm1: 836808
dcl1: 839574"
  },
  {
    "caption": "(B) Expression levels of shGFP (spliced) and GFP-EVDint/ter-GUS (unspliced) transcripts, relative to ACT2 and AT4G26410 (RHIP1), in the WT or rdr6 background. qPCR was performed on three biological replicates and error bars represent the standard error on. (*) = p-value < 0.05 (two-sided t-test against corresponding controls).",
    "ncbi_link": "shGFP: 
GFP: 
GUS: 
ACT2: 821411
AT4G26410: 828747
RHIP1: 828747
EVD: 3770632
rdr6: 824112"
  },
  {
    "caption": "(C) sRNA-seq profile mapped on the genomic 35S:GFP-EVDint/ter-GUS locus. (RPM) Reads per million. Positions indicated in nucleotides (nt) from the start of the 35S sequence. Dashed vertical lines: shGFP and GFP-GUS 3' ends.",
    "ncbi_link": "shGFP: 
GFP: 
GUS: 
EVD: 3770632"
  },
  {
    "caption": "(D) Relative expression levels of spliced and unspliced transcripts in the three EVD constructs relative to ACT2. qPCR was performed on three biological replicates and error bars represent the standard error. (ns.) = non-significant, (*) = p-value < 0.05, (**) = p-value < 0.01, (two-sided t-test between indicated samples/targets).",
    "ncbi_link": "ACT2: 821411
EVD: 3770632"
  },
  {
    "caption": "(E) High and low molecular-weight RNA analysis of EVD GAG (GAG-ex1) and EVD intron (GAG-in) in two independent T1 bulks from each indicated line. The filled arrows on the right hand-side or with an asterisk on the blots correspond to the transcripts depicted in (A-C). ACT2: loading control for mRNAs; tasiR255, miR173 and U6: loading controls for sRNAs. Hybridizations for GAG-ex2 and POL probes are found in Supp. Fig.5A.",
    "ncbi_link": "GAG: 
tasiR255: 
ACT2: 821411
EVD: 3770632
miR173: 28719308
POL: 819306
U6: 28719273"
  },
  {
    "caption": "(B) Boxplots of RNA expression levels of TEs in ddm1 from the quartiles in (A).",
    "ncbi_link": "ddm1: 836808"
  },
  {
    "caption": "(A) Comparison of RNA isoforms and sRNA patterns generated by 35S:GFP-GUS and 35S:GFP-EVDint/ter-GUS. High and low molecular-weight RNA analysis using a GFP or GUS probe in two independent transgenic lines from each construct in the WT or rdr6 background. mRNA isoforms are indicated with arrows and correspond to the transcripts depicted in Fig.2A. EtBr staining of the agarose gel and miR171 probe serve as loading control for mRNAs and sRNAs, respectively.",
    "ncbi_link": "GFP: 
GUS: 
miR171: 
EVD: 3770632
rdr6: 824112"
  },
  {
    "caption": "(C) Nucleo-cytosolic distribution of 35S:EVD and 35S:GFP-EVDint/ter-GUS RNA isoforms in rdr6 relative to that of ACT2 analyzed by qPCR. RNA extracted from Total, nuclear (Nucl) and cytoplasmic (Cyto) fractions was reverse transcribed with random hexamers and oligo(dT). snoRNA U5 is shown as a nuclear-only RNA control. (D) Same as in (C) but using exclusively oligo(dT) to reverse transcribe poly(A)+ RNAs.",
    "ncbi_link": "GUS: 
ACT2: 821411
EVD: 3770632
rdr6: 824112"
  },
  {
    "caption": "(B) RIBO-seq coverage profiles from 35S:EVD in WT or rdr6. RPM: Reads per million. (C) Ribosomal footprints on shGAG in rdr6 displaying codon occupancy at P-sites to calculate codon coverage. The coverage observed at each codon position was divided by the expected mean coverage along the entire GAG coding sequence.",
    "ncbi_link": "shGAG: 
GAG: 
EVD: 3770632
rdr6: 824112"
  },
  {
    "caption": "B Competitive inhibition of mitochondrial protein import by clogger proteins inhibits cell growths. Yeast cells expressing clogger proteins (cytochrome b2-DHFR and cytochrome b2∆19-DHFR) or cytosolic DHFR for comparison under control of the galactose-inducible promoter were grown to mid-log phase on lactate medium. Ten-fold serial dilutions were dropped on lactate (no induction) or lactate with 0.5% galactose medium (induction). MTS, matrix-targeting signal.",
    "ncbi_link": "cytochrome b2: 854950
DHFR: 854411"
  },
  {
    "caption": "E Levels of the proteasome protein Pre6 were detected upon expression of cytosolic DHFR or clogger by Western blotting and quantified from three replicates. Cells were grown in lactate medium and clogger expression was induced for 4.5 h with 0.5% galactose before samples were harvested and lysed. Data are displayed as mean ± standard deviations from n = 3 independent biological replicates.",
    "ncbi_link": "DHFR: 854411"
  },
  {
    "caption": "A The clogger was expressed in wild type (WT) and ∆rpn4 (∆) cells for 4.5 h with medium containing 0.5% galactose. Medium was exchanged for a non-inducing lactate medium. Precursor (pre) and mature (m) forms of the b2∆-DHFR clogger were visualized by Western blotting using a DHFR-specific antibody.",
    "ncbi_link": "rpn4: 851542"
  },
  {
    "caption": "G Signals of Hsp104 and Hsp42 before and after clogger induction in wild type and ∆rpn4 cells. The cytosolic soluble DHFR protein was expressed for control. The strains were grown in lactate medium and clogger expression was induced with 0.5% galactose for 6 h.",
    "ncbi_link": "DHFR: 854411
rpn4: 851542"
  },
  {
    "caption": "A Cytosolic DHFR (control) or the clogger protein b2-DHFR were expressed in wild type and ∆rpn4 cells for 4.5 h. The distribution of constitutively expressed Hsp104-GFP was visualized by fluorescence microscopy. Diameter of Hsp104-GFP-bound aggregates were quantified. . Data are displayed as mean ± standard deviations from n = 36 independent biological replicates. Significance was assessed using two-sided, paired Student's t-test. P values are indicated as asterisks ** p ≤ 0.01, **** p ≤ 0.0001. See also Fig. EV4A for quantification of the number of aggregates per cell.",
    "ncbi_link": "b2: 854950
DHFR: 854411
rpn4: 851542"
  },
  {
    "caption": "A The mitochondrial proteins Pdb1, Mam33 and Aim17 were co-expressed for 4.5 h with clogger as fusions with the red fluorescent protein RFP (mCherry). Fluorescence microscopic images of the indicated mitochondrial proteins visualized 4.5 h after induction of the clogger or cytosolic DHFR for control. For quantification of colocalization B Mutants lacking Hsp104 and Hsp42 were transformed with Aim17-expressing plasmids and grown to mid-log phase in lactate medium. Clogger expression was induced for 4.5 h with 0.5 % galactose before microscopy was perfomed. Please note that in the absence of Hsp42 and Hsp104, no Aim17-RFP-containing granules are formed. C Wild type cells were transformed with plasmids for the simultaneous expression of the clogger and an N-terminally truncated version of Mam33-RFP (both under control of GAL promoter) together with constitutively expressed Hsp104-GFP (TPI promoter) . The cells were grown on lactate plus 0.5% galactose-containing medium for 4.5 h. The distribution of the fluorescent proteins was visualized by microscopy.",
    "ncbi_link": "Aim17: 856365
DHFR: 854411
GAL: 855828
Hsp104: 850633
Hsp42: 851751
TPI: 851620"
  },
  {
    "caption": "E Clogger and Mam33-HA were co-expressed for 4.5 h in wild type and ∆hsp42 cells. Mitochondria were isolated and subjected to Western blotting to detect mature (m) and precursor (pre) forms of Mam33-HA. The matrix protein Tim16 served as loading control.",
    "ncbi_link": "HA: 
hsp42: 851751
Mam33: 854740"
  },
  {
    "caption": "G To measure the toxicity of clogger expression, clogger proteins were induced for 24 h with lactate medium containing 0.5 % galactose in the mutants indicated. Aliquots were removed and the number of living cells were assessed by a plating assay on glucose-containing plates. The resistance of ∆rpn4 to clogger expression depends on Hsp104 and Hsp42. Data are displayed as mean ± standard deviations from n = 3 independent biological replicates.",
    "ncbi_link": "Hsp104: 850633
Hsp42: 851751
rpn4: 851542"
  },
  {
    "caption": "B BAK, or BAK with cysteine introduced at the indicated positions (on a BAK∆Cys background) were stably expressed in Bax-/-Bak-/- MEFs and assess for BAK expression by immunoblotting (inset panel; * indicates non-specific band.) and apoptotic activity in response to etoposide treatment.",
    "ncbi_link": "BAK: 12018
Bak: 12018
Bax: 12028"
  },
  {
    "caption": "C E24 and R169 are proximal in inactive BAK on mitochondria. Mitochondria-enriched membrane fractions from cells were incubated with oxidant (CuPhe) and induced intramolecular disulphide linkage of BAK was assessed on non-reducing SDS-PAGE.",
    "ncbi_link": "BAK: 578"
  },
  {
    "caption": "D E24 and R169 dissociate during BAK activation. Mitochondria-enriched membrane fractions from cells were incubated with cBID (100 nM) prior to oxidant (CuPhe) and the induced intramolecular and intermolecular disulphide linkage of BAK was assessed on non-reducing SDS-PAGE.",
    "ncbi_link": "BAK: 578"
  },
  {
    "caption": "C Bax-/-Bak-/- MEFs expressing the indicated BAK variants were treated with doxycycline (Dox, 3 h), incubated for a further 24 h in the presence or absence of BH3-mimetic compounds, and cell death was assessed by PI uptake.",
    "ncbi_link": "Bak: 12018
BAK: 12018
Bax: 12028"
  },
  {
    "caption": "D Mutation of BH4 promotes BAK activating conformation change. Cells were treated with doxycycline (3 h) to induce BAK expression followed by incubation with BH3-mimetics where indicated (for 2 h) and conformation change of BAK was assessed by intracellular flow cytometry with an antibody that recognises activated BAK (G3172).",
    "ncbi_link": "BAK: 12018"
  },
  {
    "caption": "D BAK wild-type, or BAK with an engineered α1-α2 loop thrombin cleavage site were stably expressed in Bax-/-Bak-/- MEFs. Membrane fractions were incubated with thrombin prior to incubation with copper phenanthroline (CuPhe) to induce disulphide-linkage. Samples were run on SDS-PAGE under non-reducing or reducing conditions and immunoblotted for BAK with an antibody recognising the BAK N-terminus upstream of the thrombin cleavage site (aa23-38) or an antibody recognising the BH3 domain (4B5) downstream of the cleavage site. Schematic indicates the nature of the BAK protein detected by each antibody. Disulphide-linkage indicated by a hashed line. Note that the N-terminal portion of thrombin cleaved BAK could not be detected with the N-terminal antibody unless it was intramolecularly disulphide-linked. *cBID (100 nM) was added to activate BAK during thrombin cleavage. Data representative of two independent experiments.",
    "ncbi_link": "BAK: 578
Bak: 12018
Bax: 12028"
  },
  {
    "caption": "E Cleavage of the BAK α1-α2 loop potentiates MOMP. Membrane fractions from Bax-/-Bak-/- MEFs expressing BAK or BAKthrombin were incubated or not with thrombin in the presence or absence of cBID (10 nM) for the indicated times. Membrane (P) and supernatant (S) fractions were separated and immunoblotted for cytochrome c or BAK 4B5.",
    "ncbi_link": "Bak: 12018
BAK: 578
Bax: 12028"
  },
  {
    "caption": "(E) Weight  and survival curves  of neutrophil  specific  Nlrp3A350VneoR Gsdmd-/- mice. n≥18",
    "ncbi_link": "Gsdmd: 69146
Nlrp3: 216799"
  },
  {
    "caption": "(A,B) MPO staining  of liver  issue used as a marker for  myeloid cells including monocytes  in both  Nlrp3D301N-MRP8 and Nlrp3A350V-MRP8 mutant (n≥3 mice  per genotype, representative images shown, bar indicates 250 μM). H&E staining  of liver  tissue with histologic  scoring of  liver  inflammation (bar indicates 100 μM, representative images are shown). TUNEL staining  of liver  tissue (Representative images shown, bar indicates 250 μM). Data information: n≥6 mice  per genotype, significance determined by unpaired t test (* p < 0.05; ** p < 0.01; *** p < 0.001), data are expressed as mean +/− SD, dots represent individual biological replicats",
    "ncbi_link": "MRP8: 
Nlrp3: 216799"
  },
  {
    "caption": "(A) Immunohistochemical staining  of  F4/80, a marker for resident macrophages, and mRNA expression  of F4/80  in liver  tissue. Data information: Representative images shown, bar indicates 250 μM for F4/80  n≥6 mice  per genotype, significance determined by unpaired t test (** p < 0.01; *** p < 0.001), data are expressed as mean +/− SD, dots represent individual biological replicats",
    "ncbi_link": "F4/80: 13733"
  },
  {
    "caption": "(B) Immunofluorescence staining  of CLEC4F, a specific marker of  Kupffer cells, and gene expression of CLEC4F  in liver  tissue. Data information: Representative images shown, bar indicates 100 μM for CLEC4F, n≥6 mice  per genotype, significance determined by unpaired t test (** p < 0.01; *** p < 0.001), data are expressed as mean +/− SD, dots represent individual biological replicats",
    "ncbi_link": "CLEC4F: 51811"
  },
  {
    "caption": "Telomeric lncRNA levels in the indicated deletion strains as analyzed by dot blot (top) or Northern blot hybridization (bottom) using a double‐stranded telomeric probe. Telomeric dot blot signals are expressed as fold increase relative to wtA after normalization through U6 snRNA. Bars and error bars are averages and s.d. from 4 independent experiments. U6 and 18S rRNA are shown as loading controls for Northern blotting. The asterisk indicates unspliced U6. Molecular weights are on the left in kilobases.",
    "ncbi_link": "18S: 
U6: "
  },
  {
    "caption": "ARRET and αARRETNorthern blot analysis of the indicated strains using strand‐specific probes.",
    "ncbi_link": "ARRET: 
αARRET: "
  },
  {
    "caption": "Chromosome maps of differentially expressed genes in cay1Δ cells shown as fold enrichment over wt. Red dots are overexpressed genes and Tf2 retrotransposons, blue dots are overexpressed LTR sequences.",
    "ncbi_link": "Tf2: 
cay1: 2540353"
  },
  {
    "caption": "Northern blot analysis of tlh1/2+, Tf2 retrotransposons, and 18S rRNA (loading control) in wt, cay1Δ, and trichostatin A (TSA)‐treated wt cells. Black arrowhead indicates tlh1/2+ mRNA; red arrowhead unprocessed Tf2 transcripts; and blue arrowhead processed Tf2 transcripts.",
    "ncbi_link": "18S: 
Tf2: 
cay1: 2540353
tlh1: 2541932"
  },
  {
    "caption": "ChIP analysis of Cay1‐Myc binding to the indicated genomic loci. subtel: subtelomeres; Tf2: Tf2 retrotransposon genes; LTR: Tf2 LTR sequences; Tlh: tlh1/2+ genes; cen: centromeres. Immunoprecipitated DNA is normalized to input DNA and expressed as fold increase over untagged strains (unt).",
    "ncbi_link": "Tf2: 
tlh1: 2541932"
  },
  {
    "caption": "RT-PCR analysis of splicing efficiencies of the indicated pre‐mRNAs in wt and cay1∆ cells. The prp1‐1 strain carries a thermosensitive allele of the splicing factor Prp1 and was used as a positive control for splicing impairment. prp1‐1 cells were grown at 36°C for 4 h before harvesting. Amplification products corresponding to unspliced and spliced mRNAs are indicated by asterisks and gene names, respectively. rap1T indicates amplification products obtained with oligonucleotides spanning rap1+ exon 3 and thereby amplifying both spliced and unspliced mRNA. Intronless act1+ was used as a loading control. Numbers at the bottom of each panel are ratios between spliced and unspliced forms (s/u) and spliced and act1+ (s/act1). Values are expressed as fold increase over wt.",
    "ncbi_link": "act1: 
rap1: 2540115
cay1: 2540353
prp1‐1: 14217622"
  },
  {
    "caption": "Western blot analysis of Rap1-YFP protein levels in the indicated strains upon nmt1 promoter shutoff by thiamine addition. Membranes were probed with antibodies against GFP and Act1 (loading control).Quantification of Rap1-YFP protein levels in experiments as in (C). Rap1-YFP levels are expressed as fold increase over time 0 after normalization through Act1. Data points and error bars are averages and s.d. from at least four independent experiments. Statistical significance was assayed using the unpaired, two-tailed Student's t-test. *P 0.05, **P 0.01 for cay1+ versus cay1∆ samples.",
    "ncbi_link": "nmt1: 2539108"
  },
  {
    "caption": "Telomere length analysis of ApaI‐digested DNA from cay1∆trt1∆ cells harvested at increasing generation doublings (gen).",
    "ncbi_link": "cay1: 2540353
trt1: 2540601"
  },
  {
    "caption": "Northern blot analysis of ARIA, ARRET, Tf2 retrotransposons, and 18S rRNA (loading control) in the indicated strains.",
    "ncbi_link": "18S: 
ARIA: 
ARRET: 
Tf2: "
  },
  {
    "caption": "qRT-PCR quantification of TERRA levels expressed as fold increase over wt after normalization through act1+ mRNA. Bars and error bars are averages and s.d. from 3 independent experiments. Statistical significance was assayed using the unpaired, two‐tailed Student's t‐test. **P 0.01 relative to wt.",
    "ncbi_link": "act1: 
TERRA: "
  },
  {
    "caption": "Serial dilutions of the indicated strains were spotted on complete medium and grown at 30°C or 20°C. Otrt1∆ and Otrt1∆cay1∆ are strains with circularized chromosomes lacking telomeric sequence (Supplementary Fig S7).",
    "ncbi_link": "cay1: 2540353
trt1: 2540601"
  },
  {
    "caption": "Representative images of wt and cay1∆ cells grown for 24 h at 30°C or 20°C. Scale bar, 20 μm.",
    "ncbi_link": "cay1: 2540353"
  },
  {
    "caption": "Top: Examples of DAPI‐stained wt and cay1∆ cells grown in complete medium for 24 h at 30°C or 20°C. The white arrowhead indicates a chromosome bridge. Scale bar, 10 μm. Bottom: Quantification of chromosome bridges. Bars and error bars are averages and s.d. from three independent experiments and at least 200 cells were scored per sample in each experiment. Statistical significance was assayed using the unpaired, two‐tailed Student's t‐test. ***P 0.001 relative to 30°C.",
    "ncbi_link": "cay1: 2540353"
  },
  {
    "caption": "RT-PCR analysis of pre‐mRNA splicing efficiencies of rap1+ and poz1+ pre‐mRNAs in cay1+ and cay1Δ cells expressing Cay1‐YFP or Rap1‐YFP. Amplification products corresponding to unspliced and spliced mRNAs are indicated by asterisks and gene names, respectively. rap1T indicates amplification products obtained with oligonucleotides spanning rap1 exon 3 and thereby amplifying both spliced and unspliced mRNA. Intronless act1+ was used as a loading control. Numbers at the bottom of each panel are ratios between spliced and unspliced forms (s/u) and spliced and act1+ (s/act1). Values are expressed as fold increase over wt.",
    "ncbi_link": "act1: 
poz1: 2542244
rap1: 2540115
Rap1: 2540115
cay1: 2540353
Cay1: 2540353"
  },
  {
    "caption": "Western blot analysis of total proteins from early generation cay1+ and cay1Δ cells expressing Cay1‐YFP, Rap1‐YFP, and Taz1‐YFP using antibodies against Rap1, Taz1, and Act1 (loading control). Numbers at the bottom are ratios between Rap1 proteins (endogenous plus ectopic) and Act1 (Rap1/Act1). Values are expressed as fold increase over wt.",
    "ncbi_link": "Rap1: 2540115
cay1: 2540353
Cay1: 2540353
Taz1: 2542313"
  },
  {
    "caption": "Left: Representative YFPfluorescence microscopy and DIC images of cay1∆ strains expressing Cay1‐YFP. Scale bar, 10 μm. Right: Representative YFP and RFP fluorescence images of Cay1‐YFP‐ and Pot1‐RFP‐expressing cells. Arrows point to YFP and RFP foci within the same nucleus demonstrating lack of co‐localization. Scale bar, 5 μm.",
    "ncbi_link": "cay1: 2540353"
  },
  {
    "caption": "Representative YFPfluorescence microscopy and DIC images of cay1+ and cay1∆ strains expressing Rap1‐YFP. Scale bar, 5 μm.",
    "ncbi_link": "cay1: 2540353"
  },
  {
    "caption": "Northern blot analysis of ARIA, ARRET, and 18S rRNA (loading control) at early generations after expression of YFP‐tagged proteins. Numbers at the bottom are ratios between ARRET and 18S rRNA signals, expressed as fold increase over wt.",
    "ncbi_link": "18S: 
ARIA: 
ARRET: "
  },
  {
    "caption": "Serial dilutions of early generation cay1+ and cay1∆ cells expressing Cay1‐YFP and Rap1‐YFP were spotted on complete medium and grown at 30°C and 20°C.",
    "ncbi_link": "Rap1: 2540115
cay1: 2540353
Cay1: 2540353"
  },
  {
    "caption": "Northern blot analysis of Tf2 retrotransposons, U6 snRNA, and act1+ mRNA (loading control) in wt, cay1Δ, and prp1‐1 cells. prp1‐1 cells were grown at 36°C for 4 h before harvesting. Black arrowhead indicates unprocessed Tf2 transcripts. The asterisk indicates unspliced U6. Numbers at the bottom are the ratios between Tf2 and act1+ signals (Tf2/Act1) and expressed as fold increase over wt.",
    "ncbi_link": "act1: 
Act1: 
Tf2: 
U6: 
cay1: 2540353
prp1‐1: 14217622"
  },
  {
    "caption": "Northern blot analysis as in (A) in mpn1+ and mpn1∆ strains carrying a stably integrated extra copy of the snu6+ gene or empty vector control plasmids (ev).",
    "ncbi_link": "snu6: 3361572
mpn1: 2542061"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 60 weeks and analyzed by flow cytometry. The diagram displays the percentage of CLL-like cells in relation to all lymphocytesover a period of 60 weeks. Shown are mean values with ±SD. Significant differences between groups were determined by one-way ANOVA with Kruskal-Wallis test (no normal distribution) and corrected for multiple comparison with Dunn's test, **p<0.01, ***p<0.001. Summarized data from more than 40 independent experiments for individual time points, comprising n=4-75 animals per time pointand genotype. X = no surviving TCL1 x Siglecg-/-animals at the ageof 60 weeks. + indicates that in these groups only 4 animals were used for the analysis and therefore no calculation of significance was possible.",
    "ncbi_link": "Siglecg: 243958"
  },
  {
    "caption": "The percentage of B220low CD5+ leukocytes in the liver at different time points is illustrated. Besides representative dot plots show the selection of B220low CD5+ cells in the liver. Cells were pre-gated on single cells, living cells and CD45+ leukocytes. Shown are mean values with ±SD. Significant differences between groups were tested by ordinary one-way ANOVA with Šídák's post-hoc test. Data are from at least 10 independent experiments for individual time points, comprising n=5-12 animals per time point and genotype. X = no surviving TCL1 x Siglecg-/- animals at the age of 60 weeks. *p<0.05, **p<0.01, ****p<0.0001.",
    "ncbi_link": "Siglecg: 243958"
  },
  {
    "caption": "The survival of TCL1 x Siglecg-/- mice compared to TCL1 mice is illustrated with the Kaplan-Meier survival curve. (n=81 for TCL1, n=101 for TCL1 x Siglecg-/-). The groups were compared for significant differences via log-rank test.",
    "ncbi_link": "Siglecg: 243958"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 48 weeks and analysed by flow cytometry. Genotypes of the mice are: controls (Siglecg-R26ki/ki), Siglec-G overexpressing mice (Siglecg-R26ki/ki mb1cre), transgenic TCL1 controls (TCL1 x Siglecg-R26ki/ki) and transgenic TCL1 Siglec-G overexpressing mice (TCL1 x Siglecg-R26ki/ki mb1cre). Representative FACSplots show examples of stainingsof B220lowCD5+B cells (CLL-like cells) and the selected gate for B)",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958
Siglec-G: 243958"
  },
  {
    "caption": "To monitor the progression of the CLL-like population, blood was collected from the animals every four weeks up to an age of 48 weeks and analysed by flow cytometry. Genotypes of the mice are: controls (Siglecg-R26ki/ki), Siglec-G overexpressing mice (Siglecg-R26ki/ki mb1cre), transgenic TCL1 controls (TCL1 x Siglecg-R26ki/ki) and transgenic TCL1 Siglec-G overexpressing mice (TCL1 x Siglecg-R26ki/ki mb1cre). The diagram displays the percentage of B220lowCD5+cells in respect to lymphocytesover a time periodof 48 weeks. Shown are mean values with ±SD. Significant differences between groups were determined by one-way ANOVA with Kruskal-Wallis test (no normal distribution) and corrected for multiple comparison with Dunn's test. All time pointswere tested separately. *p<0.05, **p<0.01, ***p<0.001. Summarized data from more than 20 independent experiments with n=5-20 animals per time pointand genotype are shown.",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958
Siglec-G: 243958"
  },
  {
    "caption": "(C) Absolute cell numbers of B220low CD5+ lymphocytes at 36 and 48 weeks of age in the spleen are shown as mean values with ±SD. Significant differences between groups were tested by one-way ANOVA with Kruskal-Wallis test and corrected for multiple comparison with Dunn's test. The different time points were tested separately. n=8-13 animals per time point and genotype. (D) Representative dot plots show selection and percentages of B220low CD5+ B cells in the spleen pre-gated on single cells, living cells and lymphocytes. Data are from at least 10 independent experiments for individual time points. *p<0.05, **p<0.01, ***p<0.001. n=48 for TCL1 x Siglecg-R26ki/ki, n= 52 for TCL1 x Siglecg-R26ki/ki mb1cre",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958"
  },
  {
    "caption": "(E)The percentage of B220low CD5+ lymphocytes in the liver at 36 and 48 weeks of age is illustrated. Shown are mean values with ±SD. Significant differences between groups were tested by ordinary one-way ANOVA with Šídák's post-hoc test. n=7-14 animals per time point and genotype. (F) Representative dot plots for the selection of B220low CD5+ cells in the liver. Cells were pre-gated on single cells, living cells and CD45+ leukocytes. Data are from at least 10 independent experiments for individual time points. *p<0.05, **p<0.01, ***p<0.001. n=48 for TCL1 x Siglecg-R26ki/ki, n= 52 for TCL1 x Siglecg-R26ki/ki mb1cre",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958"
  },
  {
    "caption": "(G) The differences in survival are shown as Kaplan-Meier plots and log-rank test n=59 for TCL1 x Siglecg-R26ki/ki , n=57 for TCL1 x Siglecg-R26ki/ki mb1cre).",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958"
  },
  {
    "caption": "TCL1 and TCL1 x Siglecg-/- B cells were analyzed by intracellular staining with phopho-specific antibodies (or total protein detecting antibody Bcl2).",
    "ncbi_link": "Siglecg: 243958"
  },
  {
    "caption": "TCL1 x Siglecg-R26ki/ki or TCL1 x Siglecg-R26ki/ki mb1-cre B cells were analyzed by intracellular staining with phopho-specific antibodies (or total protein detecting antibody Bcl2).",
    "ncbi_link": "cre: 2777477
R26: 14910
mb1: 14999
Siglecg: 243958"
  },
  {
    "caption": "The transcript expression (normalized counts from bulk mRNA sequencing) of SIGLEC10 is given from five healthy donors, discriminating naïve CD5- (five donors), mature CD5+ 86 donors) and CD27+ memory B cell (eight donors) subsets, from CLL tumor cells (n=9) and from five paired normal residual B (NRB) cells (n=5).",
    "ncbi_link": "SIGLEC10: 89790"
  },
  {
    "caption": "(A) MCF-7 cells were co-transfected with either MIR-CNT (control plasmid) or MIR376A and GFP-LC3 plasmid, and GFP-LC3 dot formation was analyzed. White arrows indicate clusters of the GFP-LC3 dots in cells. (B) Quantification of the experiments in A. MIR376A overexpression, but not MIR-CNT expression, blocked starvation (STV)-induced autophagy (mean ± S.D. of independent experiments, n = 4, ***p<0,01). NON STV, non-starved",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(C) Overexpression of MIR376A resulted in a decrease in the autophagic activity of MCF-7 cells. Starvation-induced conversion of LC3-I to LC3-II in MCF-7 cells was analyzed. Tests were performed in the presence or absence of E64d (10 µg/ml) and Pepstatin A (10 µg/ml) (E+P). LC3-II/LC3-I densitometric ratios were marked. ACTB was used as a loading control.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(D) MIR376A blocked starvation induced SQSTM1 degradation in MCF-7 cells. ACTB was used as a loading control. SQSTM1/ACTIN densitometric ratios were marked.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(A) MIR376A blocked GFP-LC3 dot formation under starvation condition.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(A) MIR376A blocked GFP-LC3 dot formation under starvation condition. (B) Quantitative analysis of experiments in A (mean ± S.D. of independent experiments, n = 3, ***p<0,01).",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(C) Overexpression of MIR376A resulted in decreased autophagic flux in Huh-7 cells. Starvation-induced conversion of LC3-I to LC3-II was analyzed. Tests were performed in the presence or absence of E64d (10 µg/ml) and Pepstatin A (10 µg/ml) (E+P). LC3-II/LC3-I densitometric ratios were marked. ACTB was used as a loading control.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(C and D) qPCR analysis of ATG4C and BECN1 mRNA expression in control miRNA (MIR-CONT) or MIR376A overexpressing cells under non-starved (NON STV) or starved (STV) condition (mean ± S.D. of independent experiments, n = 3, *p<0,05).",
    "ncbi_link": "ATG4C: 84938
BECN1: 8678
MIR376A: 494325"
  },
  {
    "caption": "(E and F) Immunoblots showing ATG4C and BECN1 protein levels following control miRNA (MIR-CONT) or MIR376A overexpression. ACTB was used as a loading control. ATG4C/ACTB or BECN1/ACTB densitometric ratios were marked.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": "(A and B) qPCR analysis of ATG4C and BECN1 mRNA levels in MCF-7 cells transfected with control antagomirs (CNT-Ant) or antagomir-376a (Ant-376a) (mean ± S.D. of independent experiments, n = 3, **p<0,03 for ATG4C, and n = 3, **p<0,03 for BECN1). Results were expressed as fold changes against GAPDH mRNA levels.",
    "ncbi_link": "ATG4C: 84938
BECN1: 8678
GAPDH: 2597
mir-376a: 494325"
  },
  {
    "caption": "(C and D) ATG4C and BECN1 protein levels were increased following antagomir-376a (Ant-376a) transfection. ATG4C/ACTB or BECN1/ACTB densitometric ratios were marked.",
    "ncbi_link": "mir-376a: 494325"
  },
  {
    "caption": "(C and D) Normalized luciferase activity measuremets of lysates from 293T cells that were co-transfected with either MIR-CNT or MIR376A plasmids together with the wild-type or mutant luciferase constructs (mean ± S.D. of independent experiments, n = 3 for ATG4C tests, *p<0,05 and n = 5 for BECN1 tests, ***p<0,01).",
    "ncbi_link": "ATG4C: 84938
BECN1: 8678
MIR376A: 494325"
  },
  {
    "caption": "(A) Blockage of endogenous MIR376A by Ant-376a, but not CNT-Ant further stimulated starvation (STV)-activated LC3-I to LC3-II conversion in MCF-7 cells. ACTB was used as a loading control. LC3-II/LC3-I densitometric ratios were marked.",
    "ncbi_link": "MIR376A: 494325"
  },
  {
    "caption": " MIR376A and MIR376B level changes in response to starvation stress. (A and B) TaqMan quantitative PCR (qPCR) analysis of endogenous MIR376A (A) and MIR376B (B) levels under control (CNT, no starvation) or starvation (STV, 1 to 8 hours) conditions. TaqMan qPCR data was normalized using U6 small nuclear 1 (RNU6-1) (U6) mRNA levels (mean ± S.D. of independent experiments, n = 5 for both A and B, ***p<0,01).  ",
    "ncbi_link": "MIR376A: 494325
MIR376B: 574435
RNU6-1: 26827
U6: 26827"
  },
  {
    "caption": "(b) HeLa cells transfected for 24 h with control vector, or wild-type or different deletion mutants (residues 2-77, 2-275 and 232-607) of Flag-Atg16L1 were immunoprecipitated with anti-Flag antibody (Atg16L1) and immunoblotted with anti-clathrin, anti-Flag and anti-Atg5 antibodies. Clathrin interacts with the N terminus of Atg16L1, in a similar manner to Atg12-Atg5. Total lysates were run alongside as controls for protein input. FL, full-length.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(a) HeLa cells transfected for 5 days with two rounds of control, epsin 1 (eps.), clathrin heavy chain (cla.), AP2 or AP1 siRNA were either left untreated or treated for 4 h with bafilomycin A1 (+/- BafA1), after which they were lysed for western blot analysis with anti-LC3 and anti-tubulin antibodies. Note that LC3-I is often very faint compared with LC3-II in HeLa cells under the protein extraction conditions we use. However, this is not a problem because it is advisable to relate LC3-II to tubulin/actin.",
    "ncbi_link": "clathrin heavy chain: 1213
epsin 1: 29924"
  },
  {
    "caption": "(b) Ratio of LC3-II to tubulin on knockdown (KD) of control, epsin, clathrin heavy chain, AP2 or AP1, with or without bafilomycin A1, quantified from three independent experiments (two for epsin) and represented in the graph. Asterisk, P 0.01; two asterisks, P 0.001; three asterisks, P 0.0001.",
    "ncbi_link": "clathrin heavy chain: 1213
epsin: 29924"
  },
  {
    "caption": "(c) HeLa cells stably expressing GFP-mRFP-LC3 (ref. 17) were transfected for 5 days with two rounds of control or clathrin heavy chain siRNA, during which they were either left untreated (UT) or treated with bafilomycin A1 (BafA1) for the last 15 h. Cells were then fixed and analysed on a Cellomics ArrayScan system. Quantification of autophagic vacuoles (AV) or autolysosomes (AL) per cell in the different conditions is shown in the graph. Asterisk, P 0.01; n.s., not significant. n = 2,000 cells.",
    "ncbi_link": "clathrin heavy chain: 1213"
  },
  {
    "caption": "(d) HeLa cells transfected for 4 days with control, clathrin heavy chain, AP1 or AP2 siRNA were grown in Hanks balanced salt solution (HBSS) for 6 h, after which the cells were fixed and immunostained for endogenous LC3. The percentages of HeLa cells with more than 50 LC3 vesicles (marked with arrows) are quantified in the graph. End., endogenous. Three asterisks, P 0.0001. n = 500 cells. All error bars represent s.e.m. Scale bars, 10 μm. Uncropped images of blots are shown in Supplementary Information, Fig. S9.",
    "ncbi_link": "clathrin heavy chain: 1213"
  },
  {
    "caption": "(a-d) HeLa cells transfected for 72 h with control, epsin 1, clathrin heavy chain, AP2 or AP1 siRNA were treated with HBSS (to induce autophagy) for 6 h, after which they were fixed and immunostained for endogenous Atg16L1. Representative cells for the control and epsin 1 siRNA are in a, and percentages of HeLa cells with Atg16L1vesicles are quantified in b (for epsin 1), c (for clathrin) and d (for AP1 and AP2). Three asterisks, P 0.0001. Scale bars, 10 μm. (Note that we used single siRNAs for all experiments and the effects were confirmed with two independent sequences for clathrin heavy chain). n = 600 cells.",
    "ncbi_link": "clathrin heavy chain: 1213
epsin 1: 29924"
  },
  {
    "caption": "(e, f) HeLa cells transfected for 24 h with Flag-tagged wild-type Atg16L1 or the Atg16L1 deletion mutants 2-275 Atg16L1 or 232-607 Atg16L1 were fixed and immunostained with anti-Flag antibody (e); the proportions of cells with Flag-Atg16L1 vesicles are represented in f. Representative images of Atg16L1 vesicles with the different mutant constructs are shown in e. The large boxes in each panel are higher magnifications of regions in the smaller boxes. Three asterisks, P 0.0001; n.s., not significant. n = 100 cells.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(g-i) HeLa cells transfected with control, epsin 1, clathrin heavy chain, AP2 or AP1 siRNA, as above, were transfected with GFP-Atg16L1 and tomato LC3 for a further 24 h, after which the cells were fixed. g shows representative cells for control, epsin 1 and clathrin siRNA. The percentage of GFP-Atg16L1 (green) that co-localized (yellow, marked by arrows) with tomato LC3 vesicles (red) is quantified as shown in the graph in h (control, epsin 1 and clathrin siRNA) and i (control, AP2 and AP1 siRNA). Three asterisks, P 0.0001. n = 21 cells. Scale bars, 10 μm. All error bars represent s.e.m.",
    "ncbi_link": "Atg16L1: 55054
clathrin heavy chain: 1213
epsin 1: 29924
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) HeLa cells transfected for 24 h with GFP-Atg16L1 were fixed to reveal the Atg16L1 vesicles (green). Scale bar, 10 μm.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(b) HeLa cells transiently transfected for 20 h with GFP-Atg16L1 and mRFP-GPi were cultured in starvation medium for a further 2 h. TIRF image with GFP-Atg16L1 (green) and mRFP-GPi (red) is shown. Arrows indicate co-localization between Atg16L1 and GPi. The percentage co-localization of GFP-Atg16L1 with mRFP-GPi is shown in the graph. n = 2 cells. Scale bar, 5 μm.",
    "ncbi_link": "Atg16L1: 55054
GPi: 2821"
  },
  {
    "caption": "(c) HeLa cells transfected for 24 h with GFP-Atg16L1 were either left untreated or treated with 50 μM dynasore (Sigma) for 4 h and processed for immunogold electron microscopy with anti-GFP antibodies (15-nm gold particles) and anti-clathrin antibodies (10-nm gold particles). Co-localization can be seen in the boxed areas. Quantification of clathrin-coated structures (CCS) that were associated with Atg16L1 per 1,000 μm2 is shown in the graph. Three asterisks, P 0.0001. Scale bar, 100 nm. All error bars represent s.e.m.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(a) HeLa cells transfected for 24 h with GFP-Atg16L1 (green) and CFP-LC3 (blue) were incubated with Alexa Fluor-555-conjugated cholera toxin subunit B (red) for 15 min at 4 °C (allowing toxin to bind to the plasma membrane). Then cells were incubated at 37 °C (allowing internalization of cholera toxin) for 10 min and fixed for confocal analysis. Vesicles positive for both Atg16L1 and cholera toxin are yellow (also see high-magnification images at the right). Note that the small Atg16L1 vesicles co-localizing with cholera toxin are negative for LC3 (as marked with yellow arrows), and the Atg16L1 vesicles co-localizing with both cholera toxin and LC3 (marked with blue arrows) are shown in the magnified panels at the right. Scale bar, 10 μm.",
    "ncbi_link": "Atg16L1: 55054
LC3: Q9GZQ8///Q9BXW4///Q9H492///440738///81631///84557"
  },
  {
    "caption": "(b) HeLa cells transfected for 24 h with GFP-Atg16L1 (green) were incubated with Alexa Fluor-555-conjugated cholera toxin subunit B (red) as in a, after which they were fixed, immunostained for endogenous (end.) EEA1 (blue) and analysed by confocal microscopy. Vesicles positive for Atg16L1 and cholera toxin B are yellow (white arrows) and vesicles positive for both EEA1 and cholera toxin are purple (blue arrows) and are shown in the high-magnification images in the middle. The graph shows percentage co-localization. Cho. tox., cholera toxin. n = 20 cells. Scale bar, 10 μm.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(a) HeLa cells transfected for 24 h with Flag-tagged wild-type Atg16L1 or the Atg16L1 deletion mutants 2-275 or 232-607 Atg16L1, together with GFP-Atg5 and CFP-LC3, were fixed and immunostained with anti-Flag antibody before confocal analysis. Co-localization of wild-type or 2-275 Atg16L1 (red) with GFP-Atg5 (green) is marked by arrows in the insets. Scale bars, 10 μm.",
    "ncbi_link": "Atg16L1: 55054
Atg5: 9474
LC3: 440738///81631///84557"
  },
  {
    "caption": "(a) HeLa cells transfected for 24 h with GFP-Atg16L1 (green) were incubated with CellMask Orange plasma membrane stain for 5 min at 37 °C, after which they were imaged immediately (in an incubated chamber at 37 °C). A time series after fusion of a CellMask Orange vesicle (red) with a GFP-Atg16L1 vesicle (green) is shown. Scale bar, 5 μm. A higher-magnification image showing co-localization (yellow) of GFP-Atg16L1 vesicle (green) with CellMask Orange-positive vesicle (red), indicated by arrows, is also shown in the top and bottom panels.",
    "ncbi_link": "Atg16L1: 55054"
  },
  {
    "caption": "(b, c) HeLa cells transfected with control, clathrin heavy chain, AP1 or AP2 siRNA for 72 h were subsequently transfected with GFP-Atg16L1 (green) together with the siRNA for the next 24 h. The cells were then incubated for 15 min with Alexa Fluor-555-conjugated cholera toxin subunit B (red) at 4 °C, followed by further incubation for 10 min at 37 °C, after which the cells were fixed for confocal analysis (b). The co-localization (yellow) of GFP-Atg16L1 (green) with cholera toxin (red) in control or clathrin heavy-chain knockdown is shown and is quantified in the graphs in c. n = 25 cells. Three asterisks, P = 0.0002 for clathrin heavy-chain knockdown, and P 0.0001 for AP2 knockdown. All error bars represent s.e.m. Scale bar, 5 μm.",
    "ncbi_link": "Atg16L1: 55054
clathrin heavy chain: 1213
clathrin heavy-chain: 1213"
  },
  {
    "caption": "(a) HeLa cells transfected with two rounds of control, clathrin heavy chain or AP2 siRNA for 4 days were collected for immunoprecipitation (IP) with anti-Atg16L1 antibody. Western blot for total lysate (bottom) and IP (top) were performed with anti-Atg16L1 and anti-clathrin antibodies. Note the decrease in Atg16L1-clathrin interaction with AP2 knockdown. The graph shows quantification of the Atg16L1-clathrin or Atg16L1-AP2 with knockdown of control, clathrin heavy chain or AP2 from two independent experiments.",
    "ncbi_link": "clathrin heavy chain: 1213"
  },
  {
    "caption": "(b) HeLa cells transfected for 24 h with Flag-tagged wild-type Atg16L1, GFP-PLC(PH) together with empty vector (control) or dominant-negative dynamin II mutant (K44A dynamin; DN-Dyn) were fixed and analysed by confocal microscopy. Note the co-localization of Atg16L1 with PLC(PH) at the plasma membrane; this is quantified in the graph at the right. Asterisk, P 0.01. n = 20 cells. Scale bars, 5 μm. DAPI, 4′,6-diamidino-2-phenylindole.",
    "ncbi_link": "Atg16L1: 55054
dynamin II: 1785
PLC(PH): 5333"
  },
  {
    "caption": "  (D) Survival of WT, PI3Kγ null (left) and liver-specific PI3Kγ knockout mice (PI3Kγ floxtg/tg x AlbCre(tg)/tg, middle) or systemic application of the PI3Kγ inhibitor, AS605240 (right) in a model of polymicrobial sepsis induced by peritoneal contamination with a human stool suspension. Animal numbers: B6: 86 (%male: 52, %female: 48), B6-Pi3kcgko/ko: 59 (%male: 51, %female 49), B6-Pi3kcgflox/flox x AlbCre(tg)/tg: 25 (%male: 68, %female 32), FVB/N Vehicle: 25 (%male: 44, %female 56), FVB/N AS: 43 (%male: 44, %female 56)  ",
    "ncbi_link": "Alb: 11657
Cre: 2777477
Pi3kcg: 30955
PI3Kγ: 30955"
  },
  {
    "caption": "(b) Correlation analyses of RNA expression levels of uPA (PLAU gene), PAI-1 (SERPINE1 gene), and the neutrophil marker gene FPR1, and overall survival of breast cancer patients (stages 0 and 1) with high and low PLAU or SERPINE1 gene expression levels (cut-off z≥ 2.0) in the METABRIC breast cancer cohort.",
    "ncbi_link": "FPR1: 14293
PLAU: 18792
uPA: 18792
PAI-1: 18787
SERPINE1: 18787"
  },
  {
    "caption": "a, b, Representative images of GFP-LC3 puncta (autophagosomes) in skeletal (vastus lateralis) (a) and cardiac muscle (b) from GFP-LC3 transgenic mice at serial time points after exercise. Scale bar, 20 µm. c, Quantification of data (mean ± s.e.m. of 10 tissue sections) in a and b. **P  0.01, ***P  0.001 (one-way ANOVA).",
    "ncbi_link": "LC3: 67443///66734"
  },
  {
    "caption": "a, Analysis of BCL2 phosphorylation (detected by anti-BCL2 immunoprecipitation and autoradiography of 32P-labelled cells) and beclin 1 co-immunoprecipitation with BCL2 in wild-type (WT) or BCL2 AAA MEFs grown in normal media or subjected to 4 h Earle's balanced salt solution (EBSS) starvation. p-BCL2, phospho-BCL2.",
    "ncbi_link": "BCL2: 12043"
  },
  {
    "caption": "c, Representative images of GFP-LC3 puncta (autophagosomes) in skeletal and cardiac muscle of GFP-LC3 wild-type and GFP-LC3BCL2 AAA mice before exercise, after 80 min exercise, or after 75% of maximal exercise capacity. Scale bar, 20 µm. d, Quantification of data (mean ± s.d. of 4 mice per experimental group) in c.",
    "ncbi_link": "BCL2: 12043"
  },
  {
    "caption": "A Quantification of the number of OCTμDsRed2μpositive/TOM20μnegative vesicles in cells expressing GFP, GFPμparkinWT, GFPμparkinR42P, GFPμparkinK211N, or GFPμparkinC431F, treated with or without antimycin A (anti A) as in (C); both the total number (white bars) and the number colocalizing with GFPμparkin (gray bars) are indicated. Bars represent the mean ± s.e.m. Pμvalues are given first for GFPμ/GFPμparkinμpositive vesicles, then for total vesicle number (n = 49-68 cells in 2-3 experiments); ns, not significant; **P < 0.01; ***P < 0.001).",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "C HeLa cells expressing various GFP-parkin mutant contructs (green), pOCT-DsRed2 (red) and CFP-Drp1K38E were treated with 50 µM antimycin A for 2 h, then fixed and immunostained against TOM20. Arrows indicate matrix-positive/TOM20-negative structures colocalizing with GFP-parkin. Scale bars, 30 µm.",
    "ncbi_link": "Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "A Representative immunoblot of whole‐cell lysates from U2OS:GFP and U2OS:GFP‐parkin cells transfected with non‐targeting siRNA or siRNA targeting Drp1 (siDrp1).",
    "ncbi_link": "Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "B U2OS:GFP−parkin cells transfected with siRNA targeting Drp1 were treated with DMSO (upper panels) or 25 μM antimycin A (anti A, lower panels) for 90 min, then fixed and immunostained against PDH (red) and TOM20 (blue). PDHE2/E3 bp−positive/TOM20−negative MDVs colocalizing with GFP−parkin (arrows) or not (circles) are indicated. Scale bars, 20 μm (first panels on left) and 2 μm.",
    "ncbi_link": "Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "C Quantification of PDH−positive/TOM20−negative vesicles in U2OS:GFP and U2OS:GFP−parkin cells transfected with the indicated siRNA, treated with DMSO or antimycin A (anti A) as in (B); both the total number (white bars) and the number colocalizing with GFP−parkin (gray bars) are indicated. Bars represent the mean ± s.e.m. P−values are given first for GFP−/GFP−parkin−positive vesicles, then for total vesicle number (n = 48-85 cells in 2-3 experiments); ns, not significant; ***P < 0.001).",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "E Quantification of the distance between the centres of GFP−parkin−negative (black bar) or −positive (gray bar) vesicles and the edge of the nearest mitochondrial tubule for the vesicles quantified in antimycin A−treated U2OS:GFP−parkin cells transfected with siDrp1 in (C). Error bars represent the mean ± s.e.m.; *P < 0.05 (obtained by Student's t−test).",
    "ncbi_link": "Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "F U2OS:GFP‐parkin cells transfected with siRNA targeting Drp1 (siDrp1) were treated with 25 μM antimycin A for 90 min prior to fixation. Samples were immunostained against TOM20 (blue) and the indicated mitochondrial marker (red). TOM20‐negative MDVs containing the specified cargo and colocalizing with GFP‐parkin (arrows) or not (circles) are indicated. Arrowheads show lack of colocalization between GFP‐parkin and the indicated mitochondrial marker. Scale bars, 20 μm (first two columns of panels) and 2 μm (remaining columns of panels).",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "G Quantification of TOM20−negative structures that stained positively for the indicated cargo in U2OS:GFP (GFP) and U2OS:GFP−parkin (GFP−parkin) cells, transfected with siRNA targeting Drp1, treated with antimycin A (anti A); both the total number (white bars) and the number colocalizing with GFP−parkin (gray bars) are indicated. Error bars represent the mean ± s.e.m. P−values are given first for GFP−/GFP−parkin−positive vesicles, then for total vesicle number (n = 24-59 cells in two experiments; ns, not significant; ***P < 0.001).",
    "ncbi_link": "Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "AHeLa cells, transfected with siRNA targeting Drp1 and GFP‐parkin (green), were treated with 25 μM antimycin A for 90 min following a 30‐min pretreatment with 50 nM bafilomycin A1, then fixed and immunostained against PDH E2/E3 bp (red) and TOM20 (blue). PDH E2/E3 bp‐positive/TOM20‐negative MDVs colocalizing with GFP‐parkin (arrows) or not (circles) are indicated. Scale bar, 30 μm.",
    "ncbi_link": "Drp1: 10059"
  },
  {
    "caption": "CHeLa cells, transfected with GFP‐parkin (green) and siRNA targeting Drp1 and Atg5, were treated with 25 μM antimycin A for 90 min, then fixed, immunostained for PDH (red) and TOM20 (blue), and counterstained for Hoescht (gray). PDH E2/E3bp bp‐positive/TOM20‐negative MDVs colocalizing with GFP‐parkin (arrows) or not (circles) are indicated. Scale bars, 20 μm.",
    "ncbi_link": "Atg5: 9474
Drp1: 10059"
  },
  {
    "caption": "A Representative immunoblot of whole‐cell lysates from HeLa cells transfected with non‐targeting siRNA or siRNA targeting PINK1 (siPINK1), treated with 10 μM CCCP for 6 h in order to stabilize the PINK1 full‐length band.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "B HeLa cells transfected with GFP−parkin (green) and siRNA targeting PINK1 (siPINK1) or non−targeting control (ctrl siRNA), were treated with 25 μM antimycin A for 90 min, then fixed and immunostained for PDH E2/E3 bp (red) and TOM20 (blue). PDH E2/E3 bp−positive/TOM20−negative MDVs colocalizing with GFP−parkin (arrows) or not (circles) are indicated. Arrowheads indicate parkin−positive MDVs adjacent to mitochondria, possibly budding. Scale bar, 20 μm.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "A Representative immunoblot of whole‐cell lysates from U2OS:GFP and GFP‐parkin cells treated with DMSO, 25 μM antimycin A (anti A), 25 μM antimycin A with 10 μM oligomycin (anti A + oligo), or 20 μM CCCP for the indicated time period.",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "C Quantification of mitochondrial clearance in U2OS:GFP−parkin cells treated as in (A), fixed and immunostained for TOM20. Data are shown as percentage of cells containing mitochondria, by TOM20 staining, visualized by fluorescence microscopy. Error bars represent the mean ± s.e.m. (n = 3 experiments, with at least 85 cells quantified per condition, per experiment).",
    "ncbi_link": "parkin: 5071"
  },
  {
    "caption": "C Imaging of the PI4P probe GFP-2xPHOsh2 in wild type and cho1∆ cells. Images show average intensity projections of deconvolved z-stacks in which black and white pixels were inverted.",
    "ncbi_link": "cho1: 856748"
  },
  {
    "caption": "D Scatter dot plot showing PI4P levels at the plasma membrane (see experimental procedure for details of the quantification) in wild type and cho1∆ cells. Values are means ± SD, n > 100 cells, observed over 3 experiments. Mann-Whitney tests were performed.",
    "ncbi_link": "cho1: 856748"
  },
  {
    "caption": "E Ratio of PI4P average fluorescence intensity in the bud versus mother cell in the cho1∆ mutant. Values are means ± SD, n > 100 cells, observed over 3 experiments. A value > 1 indicates enrichment of the fluorescence in the bud.",
    "ncbi_link": "cho1: 856748"
  },
  {
    "caption": "F Images of Bem1-GFP in cho1∆ 9xMyc-AID-stt4 cells after 30 min treatment with or without 0.5 mM auxin. Images are average intensity projections of deconvolved z-stacks.",
    "ncbi_link": "Myc: 
cho1: 856748
stt4: 851014"
  },
  {
    "caption": "G Frequency of cells with polarized Bem1-GFP signal or Bem1-GFP in puncta in cho1∆ 9xMyc-AID-stt4 cells treated with or without auxin as shown in F. Values are means ± SD, n > 100 cells in each of 6 independent experiments. Paired Student's t-tests were performed.",
    "ncbi_link": "Myc: 
cho1: 856748
stt4: 851014"
  },
  {
    "caption": "H Images of Bem1-GFP (cyan) and Cdc24-mCherry (red) signals in cho1∆ 9xMyc-AID-stt4 cells with or without auxin. Images display maximum intensity projections of z-stacks.",
    "ncbi_link": "Myc: 
cho1: 856748"
  },
  {
    "caption": "I Maximum intensity projections of z-stacks displaying Bem1-GFP in the mutants indicated. Bem1-GFP was imaged in mss4-102 cho1∆ cells after shifting to the restrictive temperature for 30 minutes.",
    "ncbi_link": "cho1: 856748
mss4: 851789"
  },
  {
    "caption": "D Ten-fold serial dilutions of cells and subsequent colony formation on the indicated plates, where expression of wild type GALp-CDC42 is either induced in the presence of Gal or repressed in Dex. Note how mutation of the wild type Cdc42 (KKSKK) to MMSMM is lethal (see blue box), whereas appending the Bem1 BC-1 motif to this cdc42 mutant restores viability (red box).",
    "ncbi_link": "GALp: 
Bem1: 852499
cdc42: 850930
Cdc42: 850930
CDC42: 850930"
  },
  {
    "caption": "E Representative images of the mEOS-cdc42 mutants signal (cyan) after inducing the expression of GAL1p-CDC42 in the presence of Gal or repressing it in the presence of Dex. The cells in the blue and red boxes correspond to the cells in the blue and red box in panel (D). Images are average fluorescence intensity projections in which black and white pixels have been inverted.",
    "ncbi_link": "CDC42: 850930
GAL1p: 852308"
  },
  {
    "caption": "C Representative images of the indicated bem1 mutants tagged with GFP at the BEM1 locus. The inverted fluorescence images are average intensity projections.",
    "ncbi_link": "GFP: 
BEM1: 852499
bem1: 852499"
  },
  {
    "caption": "F DIC images of the indicated bem1 and cdc24 mutants showing the increased morphological defects ensuing from loss of lipid tethering in the bem1 and cdc24 mutants.",
    "ncbi_link": "bem1: 852499
cdc24: 851190"
  },
  {
    "caption": "B Global average MSD curves of mEOS-Cdc42 in the strains indicated at the Pole (P) and Non-Pole (NP) of cells. Trajectories longer than 6 frames were analyzed. Number of trajectories analyzed: BEM1 (n = 11 cells: Non Pole: 1814 tracks; Pole: 706); bem1 bc-14E px (n = 10 cells: Non Pole: 1793 tracks; Pole: 908); bem1 bc-14E (n = 13 cells: Non Pole: 1714 tracks; Pole: 975). Error bars display s.e.m. C D coefficients of mEOS-Cdc42 in the strains indicated (in box-plots displaying the median (line), the 25-75 percentiles (box) and the mean (cross)), which were compared using a non-parametric, two-tailed Mann-Whitney rank sum test. ",
    "ncbi_link": "BEM1: 852499
bem1: 852499"
  },
  {
    "caption": "C (Upper) Schematic diagram of dox-inducible shRNA system for MATR3  knockdown and MATR3  rescue in AML12  cells. (Lower)  Western blotting  detected the expression level of MATR3  after 3 days of Dox  treatment (+Dox) and followed by 3 days of Dox  removal (±Dox) in AML12  cells. Rep, replicate.",
    "ncbi_link": "MATR3: 17184"
  },
  {
    "caption": "D (Upper) Representative cross-section images showing distribution of histone  modifications  upon Ctrl and MATR3  knock down (+Dox). (Lower) Quantify the distribution pattern of histone  modifications by Standard Deviation of Pixel Intensity in cell nuclei. For H3K9me3, n=102 (Ctrl) or 84 (+Dox); for H3K9me2, n=100 (Ctrl) or 101 (+Dox); for H3K27me3, n=98 (Ctrl) or 98 (+Dox); for H3K27ac, n=117 (Ctrl) or 124 (+Dox); for H3K27me3, n=98 (Ctrl) or 98 (+Dox); for H3K4me3, n=107 (Ctrl) or 97 (+Dox). Each point represents one cell. The P values were calculated using unpaired two-tailed Student's t test; ns, not significant, *p<0.05, ****p<0.0001. Error bars indicate mean ± s.e.m.",
    "ncbi_link": "MATR3: 17184"
  },
  {
    "caption": "G (Left) Representative cross-section images showing relative distribution between AS L1  RNA with MATR3  and with histone  modification marks (H3K27me3, H3K9me3 and H3K27ac) in AML12  cells. Probes for RNA FISH were designed towards the consensus sequence of antisense L1_Mus1 RNAs. (Right) Line charts showing pixel intensity of each channel on the ROIs. Scale bars, 5μm. r, coefficient of correlation.",
    "ncbi_link": "L1: 107980437"
  },
  {
    "caption": "H Normalized average density of the marks (top) and heatmaps(bottom) for the two groups of L1  loci. The two groups are antisense L1  RNAs or sense L1  RNAs that interacted  with MATR3. L1  loci with RIP (MATR3  -IgG) count number >= 10 of antisense RNA were identified as MATR3-associated antisense L1, and the same cutoff for MATR3-associated sense L1.",
    "ncbi_link": "L1: 107980437"
  },
  {
    "caption": "A (Left) The representative cross-section image showing nuclear  distribution of MATR3  and H3K27me3 before and after 12h treating with antisense L1  ASOs in AML12  cells. (Right) Line charts showing pixel intensity of each channel on the ROIs. r, coefficient of correlation. Scale bars, 5μm.",
    "ncbi_link": "L1: 107980437"
  },
  {
    "caption": "C (Left) The representative cross-section image showing nuclear  distribution of H3K27me3 and AS  L1  RNA before and after MATR3  knockdown (Dox  treatment for 3d) in AML12  cells. (Right) The normal distribution curve for the AS  L1  pixel intensity. Scale bars, 5μm.",
    "ncbi_link": "L1: 107980437
MATR3: 17184"
  },
  {
    "caption": "E Representative images showing nuclear colocalization  of AS L1  RNAs with wild-type and truncated GFP-MATR3  proteins in AML12  cells. Scale bars, 5μm.",
    "ncbi_link": "GFP: 
L1: 107980437
MATR3: 17184"
  },
  {
    "caption": "G Representative cross-section images showing nuclear localization  of  H3K27me3 upon Ctrl, MATR3  knockdown and exogenous GFP-MATR3  (WT/△ZF1/△ZF2/△RRM1/△RRM2) overexpression in AML12  cells. Scale bars, 5μm.",
    "ncbi_link": "GFP: 
MATR3: 17184"
  },
  {
    "caption": "H Representative images of  droplet formation assays by GFP-MATR3  with different concentration (0nM, 5nM, 50nM, 200nM, 500nM) of AS L1  RNAs. GFP-MATR3  protein concentration, 3 μM. NaCl  concentration, 50mM. Scale bars, 5μm.",
    "ncbi_link": "L1: 107980437"
  },
  {
    "caption": "E Snapshot of an example region, showing Hi-C, H3K27me3 ChIP-seq and AS L1  in MATR3 RIP-seq in Ctrl and/or shMatr3 samples, using HiCExplorer. The values on the y-axis for Hi-C contact and O/E heatmap are iced normalized read counts at 100kb resolution. The values on the y-axis for ChIP-seq and RIP-seq  are average reads per million of mapped reads (RPM).",
    "ncbi_link": "L1: 107980437
Matr3: 17184"
  },
  {
    "caption": "A Representative Western blot  on chromatin  fractionation experiments of Ctrl and shMatr3 cells. Each fraction was loaded with same number of cells. GAPDH, histone H3,  Lamin A/C were used as positive controls for S1, S2  and S3, S4, respectively.",
    "ncbi_link": "Matr3: 17184"
  },
  {
    "caption": "B Genome browser view of the SAMMY-Seq  and H3K27me3 ChIP-seq in Ctrl and shMatr3 (replicate 1 and 2 merged) cells at a representative region. Gray boxes under each SAMMY-seq track showing the SAMMY-seq  domains. The shadows showing the shMatr3 loss SAMMY-seq  domains.",
    "ncbi_link": "Matr3: 17184"
  },
  {
    "caption": "H Average MATR3 RIP-seq sense and antisense signal at L1  loci around H3K27me3 domains (groups as in F) with 200kb upstream and downstream flanking regions from AML12  cells.",
    "ncbi_link": "L1: 107980437"
  },
  {
    "caption": "C MATR3  knockdown and GFP-tagged WT/S85C/F115C MATR3  protein replacement in N2A  cells. The efficiency of endogenous MATR3  knockdown and exogenous GFP-MATR3  (WT/S85C/F115C) over-expression as detected by western blotting. Representative of two independent replicates with similar results.",
    "ncbi_link": "GFP: 
MATR3: 17184"
  },
  {
    "caption": "G Representative cross-section images showing nuclear localization  of H3K27me3 upon Ctrl, MATR3  knockdown and exogenous MATR3  (WT/S85C/F115C) overexpression in N2A  cells. Scale bars, 5μm. H Standard deviation of H3K27me3 pixel intensity upon Ctrl (n=93), MATR3  knock down (n=100), GFP-MATR3  (WT) rescue (n=104), GFP-MATR3  (S85C) rescue (n=82) and GFP-MATR3  (F115C) rescue (n=120). The P values were calculated using unpaired two-tailed Student's t test; ns, not significant, *p<0.05, ****p<0.0001. Error bars indicate mean ± s.e.m.",
    "ncbi_link": "GFP: 
MATR3: 17184"
  },
  {
    "caption": "(A) survival curves of MyD88 flies injected with different doses of A. fumigatus conidia (c/f: conidia injected per fly; error bars represent mean ± SD of the survival of biological triplicates of 20 flies each).",
    "ncbi_link": "MyD88: 35956"
  },
  {
    "caption": "(B) fungal loads of single MyD88 mutant and wild-type flies (50 conidia injected per fly).",
    "ncbi_link": "MyD88: 35956"
  },
  {
    "caption": "(C-D) GFP-labeled A. fumigatus (50 conidia per fly) injected in wild-type (C) or MyD88 mutant (D) flies form hyphae in the thorax of the flies (arrows). Scale bars 50 μm.",
    "ncbi_link": "GFP: 
MyD88: 35956"
  },
  {
    "caption": "(E) expression level of Drosomycin induced by different doses of injected A. fumigatus conidia measured by RT-qPCR; M. luteus (OD=10) represents the positive control (pooled data of n=3 experiments, biological replicates).",
    "ncbi_link": "Drosomycin: 38419"
  },
  {
    "caption": "Hayan flies are susceptible to A. fumigatus. Survival (F), of Hayan mutant flies; Hayan 0h vs. 120h, (error bars represent mean ± SD of the survival of biological triplicates of 20 flies each).",
    "ncbi_link": "Hayan: 32831"
  },
  {
    "caption": "time course of fungal loads of single Hayan mutant flies (500 conidia per fly) (G), and fungal load upon death (500 conidia per fly) (H) of Hayan mutant flies; Hayan 0h vs. 120h, (error bars represent mean ± SD of the survival of biological triplicates of 20 flies each).",
    "ncbi_link": "Hayan: 32831"
  },
  {
    "caption": "(A) survival of MyD88 flies injected with ∆pptA and wild-type (Af) A. fumigatus conidia (error bars represent mean ± SD of the survival of biological triplicates of 20 flies each).",
    "ncbi_link": "pptA: 3513464
MyD88: 35956"
  },
  {
    "caption": "(B) fungal loads of single flies after the injection of 500 ∆pptA conidia.",
    "ncbi_link": "pptA: 3513464"
  },
  {
    "caption": "(E) dose response of MyD88 flies after ∆gliP (gliotoxin) mutant or wild-type [∆akuB] A. fumigatus infection; error bars represent mean ± SD of the survival of biological triplicates of 20 flies each; wild-type flies are used as a control for the dose of 250 conidia. (F-H) dose response of MyD88 and wild-type flies after gliotoxin (F), fumagillin (G), and helvolic acid (H) injection at the indicated concentrations (20 flies per condition).",
    "ncbi_link": "akuB: 
gliotoxin: 3508164
gliP: 3508164
MyD88: 35956"
  },
  {
    "caption": "(A) survival of MyD88 or wild-type flies to 250 injected ∆aspf1 (restrictocin mutant) or wild-type [∆akuB] A. fumigatus conidia (20 flies per condition); MyD88: ∆aspf1 vs. ∆akuB (***p=0.0007). (B) survival of MyD88 flies after the injection of different concentrations of restrictocin (R) (20 flies per condition ). (C-D) survival of antibiotics-treated (C) and axenic (D) MyD88 mutant flies after restrictocin injection (20 flies per condition).",
    "ncbi_link": "akuB: 
aspf1: 3505541
MyD88: 35956"
  },
  {
    "caption": "(E-F) ribosomal RNA cleavage measurement after restrictocin or PBS injection in wild-type (E) and MyD88 (F) flies; the arrowheads show the position of the 28S RNA-derived α-sarcin fragments whereas arrows on the right show its electrophoretic band position.",
    "ncbi_link": "α-sarcin: 
MyD88: 35956"
  },
  {
    "caption": "(A-B) survival (A) and fungal load (B) of Bom∆55C (55C) deficient flies compared to wild-type and MyD88 after injection of 250 conidia (error bars represent mean ± SD of the survival of biological triplicates of 20 flies each); ****p < 0.0001. (B): the fungal burden does not increase in Bom∆55C-deficient flies; wt 0h vs. 48h, **p=0.001; 55C 0h vs. 48h, **p=0.007; pooled data of n=3 experiments, biological replicates.",
    "ncbi_link": "Bom: 37102///50207///49802///37101///50206///50209///37099///37100
MyD88: 35956"
  },
  {
    "caption": "(C-D) rescue of the sensitivity of Bom∆55C flies to verruculogen (C) or to restrictocin (D) by the transgenic expression of individual 55C locus genes (caption in D also applies to (C)). 55C flies vs. BomS1, *p=0.0495, vs. BomS6 *p=0.011 for verruculogen assay (C); 55C flies vs. BomBc1 or BomS3, ****p<0.0001, 55C flies vs. BomS6, **p=0.0028 for restrictocin assay (D) (20 flies per condition).",
    "ncbi_link": "BomBc1: 37099
BomS1: 37100
BomS3: 50209
BomS6: 50206"
  },
  {
    "caption": "(E-F) expression levels of BomBc1, and BomS3 measured by RT-digital PCR 48 hours after challenge; BomBc1 PBST vs. Af, *p=0.015, PBST vs. restrictocin (R), *p=0.015; BomS3: PBST vs. Af, *p=0.02, PBST vs. R, *p=0.03 (pooled data of n=3 experiments, biological replicates).",
    "ncbi_link": "BomBc1: 37099
BomS3: 50209"
  },
  {
    "caption": "(A-B) tremor rate (A) and survival (B) of flies (20 flies per condition) overexpressing Tl[10B] in neurons compared to wild-type after injection of verruculogen. (A) Each dot corresponds to the tremor rate measured in a batch of 20 flies; tremor rate wt vs. elav> UAS-Toll10B, **p=0.002. (C-D) tremor rate (C) and survival (D) of flies (20 flies per condition) overexpressing Tl[10B] in glia compared to wild-type after injection of verruculogen. (C) Each dot corresponds to the tremor rate measured in a batch of 20 flies; tremor rate wt vs. repo> UAS-Toll10B, **p=0.002. (D) Survival wt V vs. repo> UAS-Toll10B V, **p=0.005.",
    "ncbi_link": "elav: 31000
repo: 47285
Tl: 43222
Toll: 43222"
  },
  {
    "caption": "(E-G) recovery time from tremor (E,F) and survival (G) of single flies overexpressing BomS6 ubiquitously (E,G) or in neurons (F-G) (biological replicates) compared to wild-type after injection of verruculogen; in (G) the inset represents the survival of vehicle control groups.",
    "ncbi_link": "BomS6: 50206"
  },
  {
    "caption": "(H-I) recovery time from tremor (H) and survival (I) of single flies overexpressing BomS6 in glia (pooled data from n=3 experiments, biological replicates) compared to wild-type after injection of verruculogen; in (I) the inset represents the survival of vehicle control groups. Recovery time (H) repo>mCherry vs. repo>BomS6, p=0.058, survival (I) repo>mCherry V vs. repo>BomS6 V, *p=0.016.",
    "ncbi_link": "mCherry: 
BomS6: 50206
repo: 47285"
  },
  {
    "caption": "(J-M) expression of BomS4 (J) and BomS6 (K) in head after verruculogen powder challenge, and BomS4 (L) and BomS6 (M) in head after A. fumigatus (Af), restrictocin or M. luteus injection (pooled data from n=3 experiments, biological replicates).",
    "ncbi_link": "BomS4: 37101
BomS6: 50206"
  },
  {
    "caption": "a, Western blot analysis of yeast cell lysates with polyclonal anti-flag antibody to detect flag-tagged human Beclin 1 expression. Two-hundred micrograms of protein per lane was loaded. SEY6210, wild-type yeast; JCY3000, SEY6210 disrupted in apg6/vps30; (+) control, lysates of mammalian cells transfected with flag-beclin 1.",
    "ncbi_link": "beclin 1: 8678
apg6: 855983
vps30: 855983"
  },
  {
    "caption": "c, Quantitative effects of apg6/vps30 and beclin 1 transformation on autophagicbody formation in apg6/vps30-disrupted yeast in the presence of PMSF. Cells with one or more autophagic bodies within the vacuole were scored as positive (see arrows in b). A minimum of 100 cells was counted for each sample. Results represent the mean (±s.e.m.) percentage of cells with autophagic bodies within the vacuole for triplicate samples. Similar results were obtained in five independent experiments.",
    "ncbi_link": "beclin 1: 8678
apg6: 855983
vps30: 855983"
  },
  {
    "caption": "a-f, Electron micrographs of MCF7.control (clone 38) (a, b) and MCF7.beclin1 (clone 17) cells (c- f) grown in nutrient-rich media (a, c) or subjected to 4 h of serum and amino-acid deprivation (b, d-f). Asterisks in e and f denote autophagic vacuoles that would be counted in the experiment shown in g. Autophagic vacuoles were defined as double-membrane vacuolar structures containing recognizable cytoplasmic contents. Scale bars, 1 µm.",
    "ncbi_link": "beclin1: 8678"
  },
  {
    "caption": "g, Quantitative effects of beclin 1 on basal and nutrient-deprivation-induced autophagy of MCF7 cells. Bars indicate mean (±s.e.m.) number of autophagic vacuoles per cell for cells growing in normal media (black), for cells subjected to 4 h of serum and amino-acid deprivation (grey), and for cells pre-treated for 30 min with 10 mM 3-MA and subjected to 4 h of serum and amino-acid deprivation in the presence of 3-MA (open). Mean was determined by counting the total number of autophagic vacuoles in each cell for 100 cells per clone per treatment.",
    "ncbi_link": "beclin 1: 8678"
  },
  {
    "caption": "h, Comparison of the rates of degradation of long-lived proteins in MCF7.control cells (squares, clone 38), MCF7.beclin1 cells (circles, clone 17) and MCF7.beclin1stop cells (triangles, clone 70), in EBSS + 10% serum and complete amino acids (open symbols, solid lines) in EBSS alone (closed symbols, solid lines), and in EBSS + 10 mM 3-MA (closed symbols, dotted lines). Results are mean (±s.e.m.) of triplicate wells. Similar results were obtained in three independent experiments. Results shown with these clones are representative of results obtained with other clones analysed by electron microscopy in g.",
    "ncbi_link": "beclin1: 8678"
  },
  {
    "caption": "a, Western blot analysis of flag-tagged beclin-1-transfected MCF7 clones. C, MCF7.control cells (clone 38); St, MCF7.beclin1stop cells (clone 70). Mr, relative molecular mass.",
    "ncbi_link": "beclin-1: 8678
beclin1: 8678"
  },
  {
    "caption": "b, Western blot analysis of flag-tagged beclin1stop-transfected MCF7 clones. C, MCF.control cells (clone 38); B, MCF7.beclin1 cells (clone 1).",
    "ncbi_link": "beclin1: 8678"
  },
  {
    "caption": "c, Photomicrographs of MCF7.control cells (left panel, clone 38), MCF7. beclin1 cells (middle panel, clone 17) and MCF7.beclin1stop cells (right panel, clone 70) 48 h after seeding at similar densities.",
    "ncbi_link": "beclin1: 8678"
  },
  {
    "caption": "d, Proliferation of MCF7.control cells (clones 37 and 38; closed squares and circles, respectively, solid lines), MCF7.beclin1 cells (clones 1, 6, 17; open squares, circles, triangles, respectively, solid lines) and MCF7.beclin1stop cells (clone 70, closed triangles, dotted line). Results represent mean Absorbance (A) (±s.e.m.) for six wells; similar results were obtained in three independent experiments.",
    "ncbi_link": "beclin1: 8678"
  },
  {
    "caption": "(B) Immunoblot analysis of SLC25A33 and SLC25A36 depletion in the indicated knockout (KO) and double knockout (DKO) HeLa cells (left) alongside the relative mtDNA levels of two monoclonal SLC25A33/SLC25A36 DKO cell lines calculated by qPCR (CYTB / ACTB ;right) (n=3 independent cultures).",
    "ncbi_link": "ACTB: 60
CYTB: 4519
SLC25A33: 84275
SLC25A36: 55186"
  },
  {
    "caption": "(D) Representative images taken from the arrayed CRISPR-SpCas9 screen of SLC25A33/SLC25A36 DKO cells showing one field of view from wells transfected with non-targeting control (NTC) sgRNA or TFAM sgRNA (scale bar = 20 µm)",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
SLC25A33: 84275
SLC25A36: 55186
TFAM: 7019"
  },
  {
    "caption": "(G) Relative mtDNA levels in NME4 KO and NME4/SLC25A33/SLC25A36 triple KO HeLa (left) or NME6 KO and two clones of NME6/SLC25A33/SLC25A36 triple KO HeLa (right). MtDNA calculated by qPCR (CYTB / ACTB) and presented as log2 fold change compared to levels in WT HeLa cells (n = 4-5 independent cultures).",
    "ncbi_link": "ACTB: 60
CYTB: 4519
NME4: 4833
NME6: 10201
SLC25A33: 84275
SLC25A36: 55186"
  },
  {
    "caption": "(A) The growth rate of NME6 KO and NME6 KO + NME6-MycFlag HeLa relative to WT HeLa cells incubated in DMEM containing 25 mM glucose (log2; n=13 independent cultures).",
    "ncbi_link": "Flag: 
Myc: 
NME6: 10201"
  },
  {
    "caption": "(B) Violin plot of gene effects of NME3, NME4 or NME6 depletion in 1086 cell lines from the Cancer Cell Line Encyclopaedia (CCLE) determined by CRISPR screening (DepMap 22Q2 Public+Score, Chronos; solid line denotes median, dotted line denotes 25 % quartile).",
    "ncbi_link": "CRISPR: 
NME3: 4832
NME4: 4833
NME6: 10201"
  },
  {
    "caption": "(B) Heat map representation of z-scores of log2-transformed protein intensities determined by quantitative mass spectrometry and filtered for mitochondrial proteins according to MitoCarta 3.0 The proteins shown clustered together due to their significant (permutation-based FDR < 0.05, s0 = 0.1) depletion in NME6 KO HeLa cells compared to WT and NME6 KO + NME6-MycFlag HeLa cells. OXPHOS subunits are indicated in the right column (n=4 independent cultures).",
    "ncbi_link": "Flag: 
Myc: 
NME6: 10201"
  },
  {
    "caption": "(E) Immunoblot analysis of WT HeLa cells, NME6 KO cells and NME6 KO cells expressing NME6-MycFlag (WT) or NME6H137N-MycFlag (H137N).",
    "ncbi_link": "Flag: 
Myc: 
NME6: 10201"
  },
  {
    "caption": "(F) Immunoblot analysis of WT cells and two NME6 KO clones (#1, #2) generated in three different liver cancer cell lines: HLE, Huh6 and HepG2.",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(H) The relative growth of WT and NME6 KO liver cancer cell lines monitored on each day (d) using an ATP luminescence assay. P-values for HLE cells: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = <0.0001, P-value (interaction) = <0.0001; P-values for Huh6 cells: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = 0.0005, P-value (interaction) = <0.0001;p-values for genotype are shown (n=4 independent cultures).",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(E) MtDNA-encoded transcript levels analysed by qRT-PCR in NME6 KO and NME6 KO + NME6-MycFlag cells relative to WT HeLa cells. P-values for mtDNA-encoded transcripts: two-way ANOVA P-value (transcript) = <0.0001, P-value (genotype) = <0.0001, P-value (interaction) = <0.0001 (log2; n=3 independent cultures).",
    "ncbi_link": "Flag: 
Myc: 
NME6: 10201"
  },
  {
    "caption": "(F) Nuclear DNA-encoded transcript levels analysed by qRT-PCR in NME6 KO and NME6 KO + NME6-MycFlag HeLa cells relative to WT (log2; n=3 independent cultures).",
    "ncbi_link": "Flag: 
Myc: 
NME6: 10201"
  },
  {
    "caption": "(A) Heat map of log2 transformed mean mitochondrial transcript levels of WT and NME6 KO HeLa cells incubated with 100 µM rNTPs or dNTPs for 48 h relative to untreated WT cells analysed by qRT-PCR (n=3 independent cultures).",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(B) Volcano plot representation of log2 fold change in proteins between NME6 KO cells treated with 100 µM rNTPs for 120 h and untreated NME6 KO HeLa cells determined by quantitative mass spectrometry. OXPHOS subunits are highlighted in teal (n=3 independent cultures)",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(D) Oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) of WT and NME6 KO HeLa cells incubated with or without nucleosides (100 µM) for a minimum of 120 h. Mitochondrial stress test was performed as in Fig 3A (n=3 independent experiments). P-values for OCR: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = 0.0011, P-value (interaction) = <0.0001; P-values for ECAR: two-way ANOVA P-value (time) = <0.0001, P-value (genotype) = 0.8994, P-value (interaction) = <0.0001",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(G) CYTB (top) and ND5 (bottom) transcript levels analysed by qRT-PCR in WT and NME6 KO HeLa cells incubated with the indicated nucleoside species for 48 h. P-values were calculated using a one-way ANOVA (A, adenosine; G, guanosine; C, cytidine; U, uridine; log2; 100 µM; n=4 independent cultures).",
    "ncbi_link": "CYTB: 4519
ND5: 4540
NME6: 10201"
  },
  {
    "caption": "(H) CTP (top) and dCTP (bottom) levels in the mitochondria enriched fraction of WT and NME6 KO HeLa cells incubated with the indicated nucleoside species for 120 h as determined by quantitative mass spectrometry. P-values for CTP: two-way ANOVA P-value (supplementation) = <0.0001, P-value (genotype) = <0.0001, P-value (interaction) = 0.3179; P-values for dCTP: two-way ANOVA P-value (supplementation) = <0.0001, P-value (genotype) = <0.0001, P-value (interaction) = 0.0569; P-values for supplementation are shown (C, cytidine; U, uridine; log2; 100 µM; n=4 independent cultures).",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(I) Basal (top) and maximal (bottom) oxygen consumption rates of WT and NME6 KO HeLa cells incubated with the indicated nucleoside species for a minimum of 120 h relative to untreated WT cells (A, adenosine; G, guanosine; C, cytidine; U, uridine; log2; 100 µM; n=4 independent experiments). P-values were calculated using a one-way ANOVA.",
    "ncbi_link": "NME6: 10201"
  },
  {
    "caption": "(C) Viremia progression in virus-infected mice was monitored over 2 weeks (n=11 per group). Viremia is detected with CHIKV nsP1 probe via qRT-PCR. Statistical",
    "ncbi_link": "nsP1: "
  },
  {
    "caption": "Viremia were monitored over 2 weeks. Viremia is detected with CHIKV nsP1 probe via qRT-PCR.",
    "ncbi_link": "nsP1: "
  },
  {
    "caption": "Three-week-old WT C57BL/6 mice were infected with 1E6 PFU of WT-ONNV at the metatarsal region of the footpad. (A) Viremia progression in ONNV-infected mice were monitored over 2 weeks (n=5). Viremia is detected with ONNV nsP1 probe via qRT-PCR.",
    "ncbi_link": "nsP1: "
  },
  {
    "caption": "Three-week-old WT C57BL/6 mice were vaccinated subcutaneously with 1E6 PFU of WT-CHIKV or attenuated CHIKV (RH) at the metatarsal region of the footpad. Challenge with 1E6 PFU of WT-ONNV was performed via the same route at 3 months post-vaccination. Viremia progression of the mice were monitored over 2 weeks (n=5 per group). Viremia is detected with ONNV nsP1 probe via qRT-PCR.",
    "ncbi_link": "nsP1: "
  },
  {
    "caption": "S2 cells were transiently transfected with the indicated constructs and exposed to 1% O2 for 24h. (A, B) (A) Activities of Firefly (Fluc) and Renilla (Rluc) luciferase, produce from reporter genes under control of the Ldh gene promoter, were measured in total cell extracts by dual luciferase assay and the ratio of both measures was calculated for each transfection. (B) Relative FLuc and RLuc mRNA levels were measured by RT-qPCR.",
    "ncbi_link": "Fluc: 
FLuc: 
luciferase: 
Rluc: 
RLuc: 
Ldh: 45880"
  },
  {
    "caption": "S2 cells were transiently transfected with the indicated constructs and exposed to 1% O2 for 24h. (D) Indicated stably transfected cell lines were exposed to 21% or 1% O2 for 24h before fractionation of cell extracts by ultracentrifugation on linear sucrose gradients (15%-50% The distribution of FLuc mRNA, produced from reporter genes under control of the pMT promoter was measured by northern blot in each cell types. Fractions numbers from top to bottom of the gradient are indicated.",
    "ncbi_link": "FLuc: "
  },
  {
    "caption": "(A) Control (TM3>UAS-eIF4EHP_RNAi) or eIF4EHP KD (Tub-GAL4>UAS-eIF4EHP_RNAi) flies were maintained in either normoxia or hypoxia (1%O2, 24h). Protein extracts were prepared from whole flies and eIF4EHP, LDH and Actin were detected by western blot. (B) Quantification of LDH/Actin ratio in 3 independent experiments performed as in A. Values represent mean +/- SD, n=3 biological replicates, P-value of two-ways ANOVA.",
    "ncbi_link": "eIF4EHP: 326255
GAL4: 855828
Tub: 40554"
  },
  {
    "caption": "(C) S2 cells lines inactivated for Yellow or eIF4EHP genes were established by a CRISPR-Cas9 strategy as described in the methods section. After exposure to normoxic or hypoxic conditions, cells were lysed and Actin, LDH and eIF4EHP protein levels were detected by western blot. (D) Quantification of LDH/Actin ratio in 6 independent experiments performed as in C. Values represent mean +/- SD, P-values of two-way ANOVA.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
eIF4EHP: 326255
Yellow: 30980"
  },
  {
    "caption": "(E) Cell extracts from Yellow, eIF4EHP or eIF4E6 KO cells incubated at 21 or 1% O2 were separated by centrifugation on linear sucrose gradients and Ldh mRNA was detected by northern blot in the different fractions. Fractions numbers from top to bottom of the gradient are indicated.",
    "ncbi_link": "eIF4E6: 43422
eIF4EHP: 326255
Ldh: 45880
Yellow: 30980"
  },
  {
    "caption": "B) Polysome profiles of FLuc-Ldh 3'UTR and Fluc-CA-rich 3'UTR reporter mRNA in control (Yellow KO) and eIF4EHP KO S2 cells in hypoxia.",
    "ncbi_link": "FLuc: 
Fluc: 
eIF4EHP: 326255
Ldh: 45880
Yellow: 30980"
  },
  {
    "caption": "(D) WT and eIF4EHP KO cells were co-transfected with plasmids encoding V5-tagged D. persimilis eIF4EHP (Dp eIF4EHP) or GFP, along with FLuc-Ldh3'UTR and RLuc reporters. eIF4EHP proteins were detected by western blot using eIF4EHP antibody (cross-reacting to Dp eIF4EHP).",
    "ncbi_link": "FLuc: 
GFP: 
RLuc: 
V5: 
eIF4EHP: 326255
Ldh: 45880"
  },
  {
    "caption": "(E, F) 24h after transfection, cells were cultivated in hypoxia (1%O2) for an additional 24h before measurement of luciferase activity by dual luciferase reporter assay (D) and luciferase mRNA levels by qPCR (E). Values represent mean ± SD, n=3 biological replicates, P-value of one-way ANOVA, *-P ≤ 0.05, ns- P>0.05.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(C) Cross-Linking and Immunoprecipitation experiment (CLIP) was performed on cell extracts from normoxic and hypoxic (1% O2, 24h) UV irradiated WT or eIF4EHP KO S2 cells. eIF4EHP was immunoprecipitated with eIF4EHP antibody-coated protein G sepharose beads before Ldh and Rpl32 mRNA detection by RT-qPCR in total extract (input) or immunoprecipitation eluate. mRNA enrichment levels in eluate as compared to input from 3 independent experiments were calculated as described Data represent mean +/- SD. Statistical significance was tested by two-way ANOVA followed by Sidak's multiple comparisons test, * P<0.05.",
    "ncbi_link": "eIF4EHP: 326255
Ldh: 45880
Rpl32: 43573"
  },
  {
    "caption": "(A) Female or male flies with chromosomal insertions of an UAS_eIF4EHP (BDSC 36876) RNAi construct were crossed with male or female Tub>Gal4/Tm3 (BDSC 5138) driver flies. Two hours after mating, embryos were transferred to 6% O2 (lowest tolerated O2 concentration) or kept in normoxia until eclosion. Tub-Gal4/UAS-eIF4EHP_RNAi and Tm3/UAS-eIF4EHP_RNAi F1 individuals were counted based on the presence (control) or absence (eIF4EHP KD) of the Tm3 SB marker and results were expressed as % of total eclosions for each condition. Data represent mean +/-SD fro 2 independent biological replicates. Statistical significance was tested by two-way ANOVA followed by Sidak's multiple comparisons test. **** P<0.0001; *** P<0.001; ** P<0.01; * P<0.05.",
    "ncbi_link": "eIF4EHP: 326255
Gal4: 855828
SB: 41958
Tub: 40554"
  },
  {
    "caption": "(B) Mobility of age-matched Tub-Gal4/UAS-eIF4EHP_RNAi (eIF4EHPRNAi), TM3/UAS-eIF4EHP_RNAi (control) (upper panels) or Tub-Gal4/UAS-mCherry_RNAi (m-cherryRNAi) (lower panel) females was assessed by negative geotaxis assay in normoxic conditions (21% O2) or 40 min. and 48h after an initial exposure to 1% O2 for 24h. Flies climbing past threshold within 120s were counted and expressed as % of total flies. Each assay was performed in triplicate with 20 flies. Data are mean +/- SD.",
    "ncbi_link": "m-cherry: 
mCherry: 
eIF4EHP: 326255
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "A) Expression of PTGES in normal and tumor tissue.",
    "ncbi_link": "PTGES: 9536"
  },
  {
    "caption": "B) Kaplan-Meier analysis of overall (left) and progression-free (right) survival in patients with lung adenocarcinoma with high PTGES (top 10%) and low PTGES (bottom 90%) expression.",
    "ncbi_link": "PTGES: 9536"
  },
  {
    "caption": "D) IL15 gene expression analysis in high and low NK gene signature (NK GS).",
    "ncbi_link": "IL15: 3600"
  },
  {
    "caption": "F) Overall survival in patients with high (top 50%) PTGES expression in relation to high (top 50%) and low (bottom 50%) NK cell gene expression signature.",
    "ncbi_link": "PTGES: 9536"
  },
  {
    "caption": "Death rates of wild-type and GlpK22 mutants plotted versus growth rates. Wild type is grown in glycerol minimal medium in batch cultures (black circle) and in 'chemostat' continuous cultures with growth rates coded in colors, see legend on the center right. GlpK22 mutants (white circle) are grown in glycerol minimal medium in batch culture. Data shown as mean ± (standard deviation) SD. Two replicates per condition.",
    "ncbi_link": "GlpK22: 948423"
  },
  {
    "caption": "Cell size during starvation. Length and width of the cells are measured with phase-contrast microscopy and the volume is computed considering cell shape as a cylinder with two semi-spheres, as described in the graphical synopsis at the top (see also Table EV3 and Methods). Each measurement is an average of 200 cells. (A) Measured length and width of wild type cells starved in batch cultures and previously grown in the chemostat at different steady-state growth rates and of GlpK22 cells starved and previously grown in batch culture at μ = 0.9 h − 1 (see upper color legend). Note that, as shown in Schink et al. (2019), cell widths do not change from steady state growth to starvation, while lengths decrease. Both length and width increase exponentially with growth rate. (B) Starvation volume of the cells described in panel A, computed as explained in the graphical synopsis (see also Methods). In agreement with literature (Schaechter et al., 1958), it increases exponentially with growth rate (black line).",
    "ncbi_link": "GlpK22: 948423"
  },
  {
    "caption": "Death rates of ∆rpoS mutants versus the growth rate (grey symbols), compared to wild-type E. coli K-12 (white symbols, data from Fig. 1). Death rate increases with growth rate with a smaller slope (∆rpoS: 0.57±0.13 h) compared to wild-type (WT: 0.88±0.13 h). Black and grey lines show linear weighted least square fits to log-transformed data, which take uncertainty in data points into account (see Methods). Data shown as mean ± SD. Two or three replicates per condition.",
    "ncbi_link": "rpoS: 947210"
  },
  {
    "caption": "(D) Left panel, representative  high content microscopy  image of control and RIPK2  knockdown THP-1  cells infected with S. flexneri (MOI 1:25, 8 h). Right panel, the graph depicts an average number of RIPosomes/cell, which is calculated from 3 biological replicates, Mean ± SD. ***p < 0.0005, Student's unpaired t-test.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "(E-F) Western blot  analysis of soluble  and  insoluble fractions of S. flexneri  infected (E) control siRNA and RIPK2  siRNA transfected THP-1  cells (F) Control CRISPR  (RIPK2+/+) cells and RIPK2  CRISPR knockout (RIPK2-/-) HT-29 cells.",
    "ncbi_link": "CRISPR: 
RIPK2: 8767"
  },
  {
    "caption": "(I) Representative confocal  images of RIPosomes  in  THP-1 cells infected with RFP expressing Salmonella typhimurium (MOI 1:5, 4 h). Line profile: co-localization analysis using line intensity profile. Scale bar, 8 µm. Zoom panels are digital magnifications. DNA is stained  with DAPI.",
    "ncbi_link": "RFP: "
  },
  {
    "caption": "Representative confocal  images of (M) GFP  expressing M. tuberculosis (MOI 1:10, 8 h). Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 µm. Zoom panels are digital magnifications. DNA is stained  with DAPI.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(B) Left panel, representative  high-content microscopy  images of HEK293T  cells transfected with GFP-NOD1, GFP-NOD2, and GFP  -RIPK2  plasmids for 9 h. Right panel, the graph depicts the average number of RIPosomes  per GFP-positive cell. About 15000 cells were plated per well and RIPosomes  were screened in 35 fields per well. Mean ± SD, n=3 (biological replicates), ****p < 0.00005, ordinary one-way ANOVA (Tukey's multiple comparisons test).",
    "ncbi_link": "GFP: 
NOD1: 10392
NOD2: 64127
RIPK2: 8767"
  },
  {
    "caption": "(C) Western blot  analysis of soluble  and insoluble fractions  of HEK293T  cells transfected with the CARD domain-containing region of NOD1, NOD2, and RIPK2.",
    "ncbi_link": "NOD1: 10392
NOD2: 64127
RIPK2: 8767"
  },
  {
    "caption": "(F) Representative confocal images of immunofluorescence assays conducted with THP-1 cells infected with RFP expressing S. flexneri (pseudo-colored, blue) (MOI 1:25, 8h). Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 µm. Zoom panels are digital magnifications.",
    "ncbi_link": "RFP: "
  },
  {
    "caption": "(G) Representative confocal  images of immunofluorescence  assays performed with HEK293T  cells transfected with GFP-RIPK2  and Flag-NOD2  (upper panel) or Flag-NOD1  (lower panel). Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 or 10 µm as indicated in figures. Inset zoom panels are digital magnifications.",
    "ncbi_link": "Flag: 
GFP: 
NOD1: 10392
NOD2: 64127
RIPK2: 8767"
  },
  {
    "caption": "(H-I) HEK293T  cells were transfected with (H) full length and (I) CARD domains of NOD1, NOD2, and RIPK2  followed by Western blot  analysis with soluble  and insoluble fractions using indicated antibodies.",
    "ncbi_link": "NOD1: 10392
NOD2: 64127
RIPK2: 8767"
  },
  {
    "caption": "(J-K) Western blot  analysis of soluble and insoluble fractions of RIPK2 +/+ and RIPK2-/- HT-29 cells infected with S. flexneri  (MOI 1:25, 8 h) with indicated antibodies.",
    "ncbi_link": "RIPK2: 8767"
  },
  {
    "caption": "(L-M) Representative immunofluorescence  images of doxycycline-inducible GFP-RIPK2  expressing HeLa  cells. (L) Upper panel, uninfected. Lower panel, S. flexneri -infected MOI 1:25, 4h). Immunostaining  was performed with the p65  antibody (red) and DNA stained  with DAPI  (Blue). (M) The graph indicates % of cells that are RIPosomes  positive or negative with nuclear/cytoplasmic p65  (5 fields (each group), Mean ± SD, n=3). ****p < 0.00005, Student's unpaired t-test.",
    "ncbi_link": "GFP: 
RIPK2: 8767"
  },
  {
    "caption": "(A-B) Western blot  analysis with cell lysate of uninfected and S. flexneri infected (MOI 1:25, 8 h) (A) control and ATG5  siRNA knockdown THP-1  cells, (B) wild type (WT) and ATG5  knockout (ATG5-/-) MEF  cells with indicated antibodies. Densitometric  analysis was performed using Image J software. FC, fold change.",
    "ncbi_link": "ATG5: 9474
ATG5: 11793"
  },
  {
    "caption": "(D) Left panel, representative high-content microscopy images of RIPosomes  in control and ATG5  siRNA transfected THP-1 cells infected with S. flexneri  (8 h). Right panel, the graph depicts average number of RIPosomes/cell. About 50000 cells were plated per well and RIPosomes  were screened in 35 fields per well. Mean ± SD, n=3 (biological replicates), ***p < 0.0005, Student's unpaired t-test.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(E) The soluble  and  insoluble fractions of S. flexneri infected (MOI 1:25, 8 h) control and ATG5  siRNA knockdown THP-1 cells were subjected to Western blot  analysis with indicated antibodies.",
    "ncbi_link": "ATG5: 9474"
  },
  {
    "caption": "(F) Representative confocal  images of HEK293T  cells transfected with GFP-RIPK2  and immunostained  with anti-FK2   antibodies. Line profile: co-localization  analysis using line intensity profiles. Scale bar, 3 µm.",
    "ncbi_link": "GFP: 
RIPK2: 8767"
  },
  {
    "caption": "(H) Western blot analysis of soluble  and insoluble fractions of control and p62  siRNA transfected and  S. flexneri  infected THP-1  cells (MOI 1:25, 8 h).",
    "ncbi_link": "p62: 8878"
  },
  {
    "caption": "Representative confocal  images of HEK293T  cells transfected with GFP-RIPK2  (9 h) and immunofluorescence  assay performed with antibodies specific to (K) ULK1  Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 µm or 3 µm as indicated. Zoom panels are digital magnifications.",
    "ncbi_link": "GFP: 
RIPK2: 8767"
  },
  {
    "caption": "Representative confocal  images of HEK293T  cells transfected with GFP-RIPK2  or mcherry-RIPK2  (9 h) and immunofluorescence  assay performed with antibodies specific to (L) ATG16L  (M) BECLIN1. Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 µm or 3 µm as indicated. Zoom panels are digital magnifications.",
    "ncbi_link": "GFP: 
mcherry: 
RIPK2: 8767"
  },
  {
    "caption": "(N) Luciferase assays were performed with ATG5  or p62  knockdown HEK293T  cells transfected with  NF-κB luciferase  reporter vector pGL4.32 NFκB-RE, GFP-RIPK2, and Flag-NOD1  plasmids. Mean ± SD, n=3 (biological replicates), ****p < 0.00005, ordinary one-way ANOVA (Tukey's multiple comparisons test).",
    "ncbi_link": "Flag: 
GFP: 
luciferase: 
ATG5: 9474
NOD1: 10392
RIPK2: 8767
p62: 8878"
  },
  {
    "caption": "Representative confocal  images of  THP-1 cells infected with RFP  expressing S. flexneri, (MOI 1:25, 8 h) and immunostained with, (H) IRGM  and RIPK2  antibody. Line profile: co-localization analysis using line intensity profiles. Scale bar, 5 µm. Zoom panels are digital magnifications. In image H, for better contrast, RFP  expressing Shigella  is pseudocolored to blue.",
    "ncbi_link": "RFP: "
  },
  {
    "caption": "(M) A co-IP analysis is performed with HEK293T  cell lysates expressing various domains of RIPK2  and IRGM  to map the domain/s of RIPK2 interacting  with IRGM. Asterisk indicate the main band of overexpressed protein.",
    "ncbi_link": "IRGM: 345611
RIPK2: 8767"
  },
  {
    "caption": "(O) A co-IP  analysis is performed with HEK293T  cell lysates expressing various domains of NOD1  and IRGM  to map the domain/s of NOD1 interacting  with IRGM. Asterisk indicate the main band of overexpressed protein",
    "ncbi_link": "IRGM: 345611
NOD1: 10392"
  },
  {
    "caption": "(A) Western blot analysis with the cell lysates of control CRISPR  cells and CRISPR-Cas9  mediated IRGM  partial knockout (IRGM+/-) HT-29 cells (2 clones were tested). Densitometric  analysis was performed using Image J software. FC, fold change.",
    "ncbi_link": "CRISPR: 
Cas9: 69900935
IRGM: 345611"
  },
  {
    "caption": "(B) Left panel, soluble  and insoluble fractions of S. flexneri (MOI 1:25, 8 h) infected mouse BMDMs  from Irgm1+/+ and Irgm1-/- mice  were subjected to immunoblot  analysis with antibodies as indicated. Right panel, Western blot  analysis with the colon  lysates from Irgm1+/+ and Irgm1-/- mice  with indicated antibodies. The graph indicate ratio of band intensity (measured using ImageJ) and actin (n=5, Mean ± SD, *p < 0.05, **p < 0.005, and ****p < 0.00005, Student's unpaired t-test)",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(C) Doxycycline-inducible stable GFP-RIPK2 HeLa  cells were transfected with control siRNA or IRGM  siRNA followed by infection with S. flexneri  (MOI 1:25, 4h). The cells were fixed and subjected to  high-content microscopy  to quantitate the number of RIPosomes  formed. The graph depicts an average number of RIPosome/cell. About 10000 cells were plated per well and RIPosomes  were screened in 35 fields per well. Mean ± SD, n=4 (biological replicates), ****p < 0.00005, Student's unpaired t-test.",
    "ncbi_link": "GFP: 
IRGM: 345611
RIPK2: 8767"
  },
  {
    "caption": "Western blot analysis with the cell lysate of (D) HT-29  clones stably expressing Flag-vector control or Flag-IRGM Densitometric  analysis was performed using Image J software. FC, fold change.",
    "ncbi_link": "Flag: 
IRGM: 345611"
  },
  {
    "caption": "Western blot  analysis with the cell lysate of (E)  THP-1  cells transiently transfected with GFP  or GFP-IRGM  for 6 h. Densitometric  analysis was performed using Image J software. FC, fold change.",
    "ncbi_link": "GFP: 
IRGM: 345611"
  },
  {
    "caption": "(F) Left panel, representative high-content microscopy images of NODo-RIPosomes  in HEK293T  cells transfected with GFP-RIPK2  and myc-NOD2  (upper panel) or GFP-RIPK2, myc-NOD2, and Flag-IRGM  (lower panel). Right panel, the graph depicts average number of NODo-RIPosome/cell. About 15000 cells plated per well and RIPosomes  were screened in 35 fields per well. Mean ± SD, n=5 (biological replicates), ****p < 0.00005, Student's unpaired t-test.",
    "ncbi_link": "Flag: 
GFP: 
myc: 
IRGM: 345611
NOD2: 64127
RIPK2: 8767"
  },
  {
    "caption": "(H) Representative confocal  images of HEK293T  cells transfected with mCherry  and GFP-RIPK2CARD or mCherry-IRGM  and GFP-RIPK2CARD for 9 h. Line profile: co-localization  analysis using line intensity profiles. Scale bar, 5 µm.",
    "ncbi_link": "GFP: 
mCherry: 
IRGM: 345611
RIPK2: 8767"
  },
  {
    "caption": "(L) Left panels, representative  high-content microscopy images of HEK293T  cells transfected with GFP-RIPK2  or GFP-RIPK2  and Flag-IRGM  or GFP-RIPK2  and Flag-IRGM  (S47N). The graph depicts the average number of RIPosome/cell. Mean ± SD, n=4 (biological replicates), ****p < 0.00005, ordinary one-way ANOVA (Tukey's multiple comparisons test).",
    "ncbi_link": "Flag: 
GFP: 
IRGM: 345611
RIPK2: 8767"
  },
  {
    "caption": "(C) Left panel, representative pictures of colons  of Irgm1+/+ and Irgm-/- mice  untreated or treated with GSK583  infected with  S. flexneri. Right panel, the graph depicts the average colon  lengths of the mice  groups. Mean ± SD, n=6, **p < 0.005, ***p < 0.0005, Student's unpaired t-test.",
    "ncbi_link": "Irgm: 15944
Irgm1: 15944"
  },
  {
    "caption": "(D) Representative microscopic images of H&E staining  of colon  tissues of Irgm1+/+ and Irgm-/- mice  untreated or treated with GSK583  administrated with DSS. The graph depicts the combined  histological scores. Mean ± SD, n=3 (DSS), **p < 0.005, Student's unpaired t-test. Scale bar, 200 µm",
    "ncbi_link": "Irgm: 15944
Irgm1: 15944"
  },
  {
    "caption": "(E) The soluble  and  insoluble fractionations of lysates from colon  tissues of Shigella-infected or DSS-treated Irgm1+/+ and Irgm-/- mice  treated with GSK583  as indicated, were subjected to immunoblot  analysis with indicated antibodies.",
    "ncbi_link": "Irgm: 15944
Irgm1: 15944"
  },
  {
    "caption": "b, Photograph of a representative Atg5-/- neonate compared to a wild-type littermate.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, Absence of GFP-LC3 dot formation in Atg5-/- mouse heart. Various tissues from Atg5-/- mice expressing GFP-LC3 were analysed for dot formation by fluorescence microscopy. A representative result from a neonatal heart at 3 h after birth is shown.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, Activation of AMPK in Atg5-/- mice. Hearts were isolated from unfed neonates at 0 h (lanes 1, 3, 5) and 10 h (lanes 2, 4, 6), and force-fed mice at 10 h (lane 7) after the caesarean delivery. Homogenates were prepared in the presence of phosphatase inhibitors and analysed by immunoblotting using anti-AMPK and anti-phospho-AMPK antibodies.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, ECGs from neonatal mice at the indicated time after caesarean delivery. ST elevation was observed in all Atg5-/- mice (n = 4) at 8-9 h after delivery.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, TNF-α-mediated processing of humanATG16L1 in monocyte-derived macrophages. Scatter plot of immunoblot densitometry depicts a ratio of cleaved:full-length ATG16L1 (Extended Data Fig. 2). n = 7 donors.",
    "ncbi_link": "ATG16L1: 55054"
  },
  {
    "caption": "a, HeLa cells transfected with control siRNA (siCTL) or siCaspase 8 were stimulated with 2.0 μM staurosporine or 20 ng ml−1 TNF + 10 μg ml−1 CHX.",
    "ncbi_link": "Caspase 8: 841"
  },
  {
    "caption": "b, HeLa cells transfected with control siRNA or siCaspase 9 were stimulated as in a.",
    "ncbi_link": "Caspase 9: 842"
  },
  {
    "caption": "c, HeLa cells transfected with control, caspase-3- or caspase-7-specific siRNAs were stimulated with 20 ng ml−1 TNF + 10 &mgr;g ml−1 CHX.",
    "ncbi_link": "caspase-3: 836
caspase-7: 840"
  },
  {
    "caption": "d, Wild-type or caspase-3-knockout macrophages were stimulated with 2.0 µM staurosporine or 20 ng ml−1 TNF + 10 µg ml−1 CHX. Data in a-c represent 2 independent experiments; data in d represent 4 independent experiments.",
    "ncbi_link": "caspase-3: 12367"
  },
  {
    "caption": "e, Caspase 3 activity in murine macrophages following glucose starvation, n = 3 mice. RLU, relative light units.",
    "ncbi_link": "Caspase 3: 12367"
  },
  {
    "caption": "f, Quantification of mean LC3-II area in wild-type (Casp3+/+) or Casp3-knockout (Casp3−/−) macrophages, n = 3 mice. Data in a-f represent 2 independent experiments.",
    "ncbi_link": "Casp3: 12367"
  },
  {
    "caption": "f, Measurement of cytokine mRNA transcripts in mesenteric lymph nodes. Data are pooled from 2 independent experiments of 3 mice (PBS) and 7 mice (Y. enterocolitica) per experiment. Transcripts are normalized to Gapdh (2−Dgr;Ct).",
    "ncbi_link": "Gapdh: "
  },
  {
    "caption": "B Immunofluorescent staining confirmed the absence of MeCP2 in MECP2-KO PSCs, NPCs, and neurons. Scale bar = 10 µm.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "C RT-qPCR array revealed differential gene expression between control and MECP2-KO 28-day neurons. The P values are calculated based on a Student's t-test of the replicate 2-ΔΔCt values for each gene in the control group and KO groups (WT83/Q83X cell lines were used; N = 3 clones from each genotype).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "F Violin plots of selected genes showing the comparison between control and MECP2-KO neurons from the single-cell analyses (log2(expression) values) that overlapped with the results obtained via RT-PCR array.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "D, E Western blot quantification showed decreased presynaptic Synapsin1 (D) and postsynaptic PSD-95 (E) in untreated 6-week MECP2-KO neurons that can be increased by drug treatment (Kruskal-Wallis test, *P < 0.05, **P < 0.01, ***P < 0.001; full Western blot, Fig EV4A) (WT83/Q83X cell lines were used; N = 3 clones from each genotype).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "F, G 6-week MECP2-KO neurons (F) showed a pharmacologically rescuable reduction of co-localized synaptic puncta (G; one-way ANOVA, F16,118 = 9.148, *P < 0.05; Dunnet's multiple comparisons test vs untreated KO (WT83/Q83X cell lines were used; N = 7-8 neurons/condition). *P < 0.05, **P < 0.01, ***P < 0.001. Z scores relative to KO untreated: Control = 3.903; Nefiracetam = 3.560; Carbamoylcholine = 2.705; Pirenzepine = 0.0448; PHA543613 = 2.121; Acamprosate = 3.339; Baclofen = 0.5672; GR73632 = 2.237; Hyperforin = 3.016, and IGF-1 = 3.791. Scale bar = 5 µm.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "I Treatment with either Nefiracetam or PHA 543613 increased network spiking activity in MECP2-KO neurons on MEA (two-sided unpaired Student's t-test compared to KO untreated: Nefiracetam, *P = 0.016 and Z = 2.418; PHA 543613, *P = 0.027 and Z = 2.147; Acamprosate, P = 0.39 and Z = 0.477; WT83/Q83X and WT82/K82fs cell lines were used; N = 4-11 MEA wells/condition).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "B, C Immunofluorescent staining (B) and quantitation (C) confirmed the graded decrease in MeCP2 expression from control to 50% MECP2 mosaic to full MECP2-KO neurospheres. Scale bar = 50 µm.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": " D 8-week MECP2-KO neurospheres (N = 44) exhibited decreased size (diameter; **P < 0.01), but 50% MECP2-mosaic neurospheres (CTR/KO; N = 44) were unchanged from controls (one-way ANOVA, F2,150 = 6.03, P = 0.003; Dunnett's multiple comparisons test; N = 65). Left: representative brightfield images of neurospheres; Right: neurosphere size quantification. Scale bar = 200 µm. ",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": " E Calcium imaging analysis showing calcium transients normalized by control (one-way ANOVA, F2,72 = 15.62, P < 0.0001; Dunnett's multiple comparisons test vs control: MECP2-mosaic, ***P < 0.001; MECP2-KO, ***P < 0.001). WT83/Q83X cell lines were used; N = 44 Q83X neurospheres and 65 WT83 neurospheres. ",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "RNA sequencing (D, left: heatmap) and GO analysis (D, right) of untreated MECP2-KO organoids vs Nefiracetam (N = 4 samples each of ~10-15 pooled organoids) indicated that treatment upregulated genetic expression in synapse-relevant pathways.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "RNA sequencing (F, left: heatmap) and GO analysis (F, right) of untreated MECP2-KO organoids vs PHA 543613 (N = 4 samples each of ~10-15 pooled organoids) indicated that treatment upregulated expression of genes in synapse-relevant pathways.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "MECP2-KO and control organoids had proportions of cells positive for the neuronal marker NeuN (I; Student's t-test, t14 = 0.26, P = 0.80, N = 8 each)",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "J MECP2-KO and control organoids had proportions of cells positive for cortical layer V and VI neuronal marker CTIP2 (J; one-way ANOVA, F3,40 = 2.489, P = 0.074 and Z < 1, WT83/Q83X and WT82/K82fs cell lines were used; N = 8-14 organoids each). J, left: representative image of CTIP2+ immunofluorescent staining in cortical organoids; J, right: quantification of CTIP2+ neurons. Scale bar = 50 µm.",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "L; left and center: representative population spiking traces of control and MECP2-KO organoids; right: quantification of organoid population spiking activity, N = 6 replicates each).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "Drug treatment increased spiking network activity of MECP2-KO cortical organoids to a level not significantly different from that of control organoids (M; one-way ANOVA, F3,31 = 3.775, Dunnett's multiple comparisons test vs control: untreated KO, **P < 0.01 and Z = 3.192; Nefiracetam, P = 0.98 and Z = 2.117; PHA 543613, P = 0.12 and Z = 1.101, WT83/Q83X cell lines were used; N = 7-10 MEA wells per condition).",
    "ncbi_link": "MECP2: 4204"
  },
  {
    "caption": "(B) Single confocal sections of HeLa cells infected with GFP-expressing ΔsseL mutant bacteria (blue) for 10 h and immunolabelled for ubiquitin (all chain types - Ub, red) and lysine-48-linked (K48-Ub, green) or lysine-63-linked (K63-Ub, green) ubiquitin chains (false coloured, scale bars, 5 µm). Arrows indicate SCV-associated ubiquitin and K63-Ub labelling.",
    "ncbi_link": "sseL: 1253809"
  },
  {
    "caption": "SseL DUB activity reduces the recruitment of ubiquitin and autophagic markers to Salmonella microcolonies.Single confocal sections of HeLa cells infected with GFP-expressing ΔsseL mutant bacteria (blue) for 12 h and immunolabelled for ubiquitin (Ub, red) and (A) p62 (green) or (B) LC3 (green) (false coloured, scale bars, 5 µm). The far right panels show merged images of p62 or LC3, ubiquitin and Salmonella. Arrows indicate SCV-associated ubiquitin labelling with p62 or LC3.",
    "ncbi_link": "sseL: 1253809"
  },
  {
    "caption": "(A) Quantification of the percentage of infected cells with SCV-associated ubiquitinated aggregates. HeLa cells were infected with ΔsseL mutant bacteria for 12 h. At 8 h post-infection, cells were subjected to the indicated treatments for 4 h before fixation and immunolabelling. A minimum of 50 cells were counted per condition in each experiment and values are the mean ± SEM of at least 3 independent experiments. p values are relative to the mean value of mock-treated cells. * p<0.05; ** p<0.01; *** p<0.001.",
    "ncbi_link": "sseL: 1253809"
  },
  {
    "caption": "(B) Single confocal sections of HeLa cells infected with GFP-expressing ΔsseL mutant bacteria (blue), treated and processed as in (A) and analysed by fluorescence microscopy for ubiquitin (Ub, red) and LC3 (green) (scale bars, 5 µm). The far right panels show merged images of LC3, ubiquitin and Salmonella.",
    "ncbi_link": "sseL: 1253809"
  },
  {
    "caption": "(B) Quantification of infected macrophages containing ubiquitinated aggregates 10 h after bacterial uptake. Cells were processed as in (A) and analysed by fluorescence microscopy. A minimum of 50 cells were counted for each bacterial infection per experiment and values are the mean ± SEM of at least 3 independent experiments. * p<0.05; *** p<0.001. Uninfected cells (uninf) were from the same wells as infected and therefore were exposed to extracellular bacteria. (C) Immunoelectron microscopy of RAW264.7macrophages infected with the ΔsseL mutant bacteria for 12 h. Arrows and arrowheads indicate ubiquitin (15 nm gold particles) and p62 (10 nm gold particles), respectively (scale bar, 0.5 µm).",
    "ncbi_link": "sseL: 1253809"
  },
  {
    "caption": "(B) Quantification of the number of puromycin-induced ubiquitin inclusions in cells. HeLa cells were transfected with a vector expressing myc-SseL or myc-SseLC/A for 16 h followed by treatment with puromycin (5 µg/ml) for 4 h and immunolabelled with anti-myc, anti-p62 and anti-ubiquitin. 50 individual cells were counted per condition in each experiment. Values are the means ± SEM of at least 3 independent experiments. ** p<0.01.",
    "ncbi_link": "SseL: 1253809"
  },
  {
    "caption": "(C) Single confocal sections of HeLa cells transfected with a vector expressing myc-SseL for 16 h followed by treatment with puromycin (5 µg/ml) for 4 h and immunolabelled with anti-myc (blue), anti-p62 (green) and anti-ubiquitin (Ub, red) (scale bars, 5 µm). The lower panels show a merged image of p62, ubiquitin and myc-SseL. Arrows indicate ubiquitin and p62 aggregates present in untransfected cells and arrowheads indicate cells expressing myc-SseL",
    "ncbi_link": "SseL: 1253809"
  },
  {
    "caption": "SseL interacts with p62 and autophagic substrates.(A and B) Co-immunoprecipitation from RAW264.7 macrophages infected with ΔsseL mutant bacteria expressing SseL-HA or SseLC/A-HA for 10 h. (A) Infectedcell lysates and immunoprecipated fractions were probed with anti-HA, anti-ubiquitin and anti-p62 antibodies. (B) At 7 h post-infection, infected cells were subjected to mock, 3-MA or starvation (Stv) treatments for 3 h before harvesting and processing as described in (A). Cell lysates and immunoprecipiations were probed with anti-HA and anti-ubiquitin antibodies.",
    "ncbi_link": "SseL: 1253809
sseL: 1253809"
  },
  {
    "caption": "D Immunoblot analysis of c-myc-/- HO15.19 rat fibroblasts infected with retroviral vectors expressing the indicated Myc proteins. Parental TGR1 cells serve as control for endogenous  levels of the MycWT protein.",
    "ncbi_link": "Myc: 4609"
  },
  {
    "caption": "A  3T9 fibroblasts expressing the indicated MycER proteins and control cells (EV) were treated with OHT (4h) and subjected to biochemical fractionation in three independent experiments. The quantity of MycER protein in the different fractions was quantified by western blotting (shown in Fig. EV4A) and the relative proportion in the various fractions plotted as average and standard deviation.",
    "ncbi_link": "ER: 
Myc: 4609"
  },
  {
    "caption": "F Percentage of promoters with the indicated DNA motifs under the ChIP-seq peak (±100 bp from the peak summit) within each regulatory class (no DEG, UP or DOWN) for either MycERWT (left) or MycERHEA (right). p-values calculated with Fisher's exact test.",
    "ncbi_link": "Myc: 4609"
  },
  {
    "caption": "Jurkat cells were exposed to either DMSO, or dieldrin in DMSO for 30 min. RNA-seq was then performed on cDNA libraries prepared after depletion of ribosomal RNAs. Jurkat T cells were treated with either DMSO (vehicle) or 100μM dieldrin for the indicated times. Abundance of IL2 mRNA was assessed by RT-qPCR. Data shown are means +/- SEM from four independent experiments. Significance (p-value) was estimated using the two-sided student t test appropriate for small sample numbers. ***: p-value<0.001.",
    "ncbi_link": "IL2: 3558"
  },
  {
    "caption": "Jurkat cells were exposed to either DMSO, or dieldrin in DMSO for 30 min. RNA-seq was then performed on cDNA libraries prepared after depletion of ribosomal RNAs. Screen captures from IGV showing increased divergent transcription inside a HERV sequence upon exposure of the Jurkat cells to dieldrin in the intergenic region between MUC21 and MUC22. Color code as in (A).",
    "ncbi_link": "MUC21: 
MUC22: "
  },
  {
    "caption": "GSC neurospheres were dissociated to single cell suspension and transfected with either miR-10b inhibitor (labeled \"miR-10b-i\") or non-targeting control oligonucleotide, or treated with Lipofectamine 2000 only (Mock). Statistical significance of the difference was determined by Student's t test, with p-values < 0.001 indicated by three asterisks. Numbers of replicates and exact P-values are included in Appendix Table S4.A. Cell viability was monitored at day 5 after transfection as described in Materials and Methods.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "C. MiR-10b inhibition induces cleavage of caspases 3 and 7 in GSC, as determined by Western blot analysis at day 5 after transfection with the inhibitor. The signals were quantified using ImageJ and normalized to beta-actin.",
    "ncbi_link": "MiR-10b: 406903"
  },
  {
    "caption": "D. Flow Cytometry analysis of Annexin V and 7-AAD staining of GSC GBM8 at day 5 after miR-10b inhibition.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "Three types of GSC (GBM4, GBM6, and GBM8) were transfected with miR-10bASO, and gene expression was analyzed 24 hours later by the Affymetrix microarrays. The heatmaps colors intensity demonstrate altered expression of the genes (up- or down-regulated relative to the mock treated samples) with the fold change > 1.2 and p < 0.05 in at least two out of the three GSC cultures.A. The genes associated with \"cell cycle\" bioterm have been selected using Ingenuity Pathway Analysis. The treatment with the miR-10b inhibitor is indicated as \"miR-10b-i\".",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "B. The genes associated with \"RNA splicing\" bioterm have been selected using Gene Ontology (GO). The treatment with the miR-10b inhibitor is indicated as \"miR-10b-i\". Arrows depict the genes selected as candidate direct targets for further study.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "C. miR-10b binding motifs are enriched in 5'UTRs of the genes up-regulated by miR-10b ASO. The graph shows the probability that enrichment of the miR-10b motifs in mRNAs up-regulated vs. unchanged (p<0.05) by anti-miR-10b does not occur by chance.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "D. The miR-10b octamer motifs' composition of the 5'UTRs was compared between transcripts up- and down-regulated on the microarrays. The relative frequencies of various miR-10b binding motifs are shown, indicating that mostly miR-10b 3'-end binding motifs are enriched in the up-regulated mRNAs.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "Figure 3.Expression analysis of splicing factor mRNAs in various GBM datasets.A. The genes encoding splicing factors down-regulated by miR-10b are expressed at lower levels in various GBM datasets relative to their expression in normal brain tissues.B. In contrast, many splicing factors up-regulated by miR-10b are overexpressed in the GBM datasets.Six high-content GBMmicroarray datasets from the Oncomine resource (https://www.oncomine.org/resource/main.html), including TCGA_BrainGBM (2), Bredel Brain2 (31), Lee Brain (32), Liang Brain (33), Murat Brain (34) and Sun Brain (35), that collectively contain information for 858 GBM and 52 control samples, have been utilized for the analysis. The data is presented as log2 fold change between GBM and normal brain tissues.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "B. qRT-PCR analysis validates that mRNA of MBNL1-3, SART3, RSRC1 and other splicing factors are de-repressed by miR-10b ASO in different GSC and GBM cell lines. mRNA expression levels were normalized to GAPDH expression.",
    "ncbi_link": "GAPDH: 
MBNL1: 4154
miR-10b: 406903
RSRC1: 51319
SART3: 9733"
  },
  {
    "caption": "C. Regulation of representative splicing-related proteins by miR-10b mimic in GSC, as demonstrated by Western blot analysis. The signals were quantified using ImageJ and normalized to beta-actin. The ratios between miR-10b mimic expressing and control samples are indicated.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "D. miR-10b mimic regulates 5'UTR Luciferase reporter containing a single miR-10b complementary site.",
    "ncbi_link": "Luciferase: 
miR-10b: 406903"
  },
  {
    "caption": "E. miR-10b mimic regulates 5'UTR Luciferase reporters of some splicing factors genes bearing wild type (WT), but not mutated (Mut) miR-10b binding sites. Statistical significance of the differences was determined by Student's t test, with p-values < 0.05 indicated by asterisks, p < 0.01 by two asterisks, and p< 0.001 by three asterisks. Numbers of replicates and exact P-values are included in Appendix Table S4.",
    "ncbi_link": "Luciferase: 
miR-10b: 406903"
  },
  {
    "caption": "B. 2'-O-MOE-POmiR-10b inhibitor (miR-10b-i) or non-targeting control (1 μg of each) formulated with InVivo-jet PEI were injected intratumorally at days 20 and 25 after cells implantation. The efficacy of miR-10b inhibition was assessed by qRT-PCR analysis of the resected tumors, with miR-10b expression levels normalized to miR-125b.",
    "ncbi_link": "miR-125b: 
miR-10b: 406903"
  },
  {
    "caption": "C. qRT-PCR analysis demonstrates that miR-10b inhibition in orthotopic GBM8 leads do de-repression of its mRNA targets. mRNA expression levels were normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
miR-10b: 406903"
  },
  {
    "caption": "D. Inverse correlation between miR-10b levels and expression of its mRNA targets in resected GBM8 tumors.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "E. Inhibition of miR-10b markedly reduces tumor burden. The left panels illustrate tumor imaging in representative animals at day 29. The bars represent average signal ratios for each group at day 29 (after treatment) to day 20 (at the beginning of treatment). N = 7 animals per group at treatment initiation.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "B-D. Systemic inhibition of miR-10b markedly reduces tumor burden. Uncomplexed 2'-O-MOE-PSmiR-10b inhibitor (miR-10b-i) or non-targeting control of the same chemistry were injected at 80 mg/kg through the tail vein at the days indicated by arrows.B. The left panels illustrate tumorimages of representative animals at day 34, and average signals (photons/sec) are indicated below the images. The bars represent average signal ratios for each group at day 34, relative to day 6",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "B-D. Systemic inhibition of miR-10b markedly reduces tumor burden. Uncomplexed 2'-O-MOE-PSmiR-10b inhibitor (miR-10b-i) or non-targeting control of the same chemistry were injected at 80 mg/kg through the tail vein at the days indicated by arrows.B. The left panels illustrate tumorimages of representative animals at day 34, and average signals (photons/sec) are indicated below the images. The bars represent average signal ratios for each group at day 34, relative to day 6.C. Each mouse was sacrificed when the tumor-generated signal reached 5X107 photons/sec, and Kaplan-Meier survival plots were built retrospectively.D. Growth curves of individual tumors based on the ratios of bioluminescence signals to the baseline signals at day 6.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "E. The efficacy of miR-10b inhibition in intracranial tumors was assessed by qRT-PCR analysis of the resected tumor tissues, with miR-10b expression levels normalized to miR-125b.",
    "ncbi_link": "miR-125b: 
miR-10b: 406903"
  },
  {
    "caption": "F. qRT-PCR analysis demonstrates that miR-10b targets were de-repressed in orthotopic GBM8 upon systemic administration of the miR-10b inhibitor. Seven tumors per condition, and two specimens per tumor have been analyzed. mRNA expression levels were normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
miR-10b: 406903"
  },
  {
    "caption": "G. Inverse correlation between miR-10b levels and expression of its mRNA targets in resected GBM8 tumors.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "B-D. Systemic treatment of intracranialGBM8tumors with uncomplexed 2'-O-MOE-PSmiR-10b inhibitor (miR-10b-i) or non-targeting control oligonucleotide (at 80 mg/kg) was not associated with toxic effects.B. No significant difference in average mice weight was observed between the anti-miR-10b and control treatment groups.C. No significant difference in average organs' weight was observed between the anti-miR-10b and control treatment groups.D. No significant difference in tissue histology using Hematoxylin and Eosin staining was observed between the anti-miR-10b and control treatment groups.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "A. Continuous osmotic delivery of miR-10b inhibitor markedly reduces tumor burden. The osmotic pumps, loaded with lipid nanoparticles formulated with 2'-O-MOE-POmiR-10b inhibitor or non-targeting control infused 2 μg of the oligonucleotides per day introtumorally, over 13 days. Tumors growth was monitored by the WBI, and the left panels illustrate tumor imaging of representative animals at the end of treatment. The bars represent average signal ratios for each group at day 13 (end of treatment), relative to day 2 (treatment initiation).",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "F. Quantitative immunostainings analysis indicates that proliferation and apoptosis markers are affected by anti-miR-10b treatment. No significant effect on invasion of intracranial GBM8 was observed.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "A, B. miR-10b inhibition decreases GL261 cellviability. Cellviability was measured at days 3-7 after transfection with miR-10b inhibitor, non-targeting control, or Lipofectamine 2000 alone (mock).A. Phase contrast photographs of GL261 cultures at day 6 post-transfection.B. Growth curves of cultured GL261 cells, based on the viability assay.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "C. InVivo-jet PEI - formulated 2'-O-MOE-PS/PO miR-10b inhibitor or non-targeting control were infused to orthotopic GL261 tumors by osmotic pumps, starting at day 6 after cell implantation. The uptake of ASOs was confirmed by IHC for PS-containing oligonucleotides (green). GL261 tumor cells expressing M-Cherry are red.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "D. Osmotic delivery of miR-10b inhibitor markedly reduces GL261tumorgrowth in immunocompetent Black 6 Albino mice. Micephotographs show tumor imaging in representative animals at day 3 after pump implantation, and average signals in photons per second are indicated. Tumorgrowth rates were calculated as ratios of the signals at day 3 of the treatment to day 1 prior to initiation of the treatment.",
    "ncbi_link": "miR-10b: 406903"
  },
  {
    "caption": "E. The efficacy of miR-10b inhibition in intracranial tumors was assessed by qRT-PCR analysis of the resected tumor tissues, with miR-10b expression levels normalized to miR-125b.",
    "ncbi_link": "miR-125b: 
miR-10b: 406903"
  },
  {
    "caption": "F. qRT-PCR analysis demonstrates that miR-10b target p21 was de-repressed in GL261 tumors upon miR-10b inhibition. mRNA expression levels were normalized to GAPDH.",
    "ncbi_link": "GAPDH: 
p21: 12575
miR-10b: 406903"
  },
  {
    "caption": "A-C AID expression was analyzed in colon and pancreatic human cell lines (A) qRT-PCR analysis of AID expression in LoVo and SW480 colon cell lines. n = 5 (LoVo); 3 (SW480). **P-value: LoVo: 0.0017; SW480: 0.0079. (B) qRT-PCR analysis of AID expression in AsPC and PaTU-8988S pancreatic cell lines (n = 2). *P-value: AsPC: 0.0369; PaTU-8988S: 0.0119.",
    "ncbi_link": "AID: 57379"
  },
  {
    "caption": "A-C AID expression was analyzed in pancreas explants from C57BL/6 mice. Samples were treated as indicated with 50 ng/ml TNF-α. (C) qRT-PCR analysis of AID expression in pancreatic explants from wild-type mice (n = 3). *P = 0.0242.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "D AID−/− or AID+/− mice were treated with 3% DSS for 10 cycles, and colonic sections were analyzed by histology inspection after H/E staining. Graphs represent mean frequency values of adenoma and adenocarcinoma lesions of five independent experiments. n = 28 (AID−/− males); 35 (females); 23 (AID+/− males); 25 (females). P-value: male: 0.8; female: 0.246.",
    "ncbi_link": "AID: 11628"
  },
  {
    "caption": "GFP immunofluorescence in colonic and pancreatic tissue from R26AID+/KIVillinCRE+/TG and R26AID+/KIp48CRE+/KI mice. Scale bar: 50 μm.",
    "ncbi_link": "CRE: 
AID: 11628
p48: 16391
Villin: 22349"
  },
  {
    "caption": "qRT-PCR analysis of AID expression in colonic and pancreatic tissue from R26AID+/KIVillinCRE+/TG and R26AID+/KIp48CRE+/KI mice. n = 5 (R26AID+/+ VillinCRE+/TG); 4 (R26AID+/KIVillinCRE+/TG); 2 (R26AID+/+p48CRE+/KI); 2 (R26AID+/KIp48CRE+/KI). LPS+IL4-stimulated B cells are shown as a positive control (n = 2). Bars show mean values ± SEM normalized to LPS+IL4-treated B cells.",
    "ncbi_link": "AID: 11628
p48: 16391
Villin: 22349"
  },
  {
    "caption": "Kaplan-Meier survival curves for R26AID+/KIVillinCRE+/TG (left) (n = 47 (R26AID+/+ VillinCRE+/TG); 38 (R26AID+/KIVillinCRE+/TG)) and R26AID+/KI p48CRE +/KI mice (right) (n = 39 (R26AID+/+p48CRE+/KI); 23 (R26AID+/KIp48CRE+/KI)).",
    "ncbi_link": "AID: 11628
p48: 16391
Villin: 22349"
  },
  {
    "caption": "A, B Analysis of AID mutagenic activity in Elastase1 (A) and Elastase2a (B) by next-generation sequencing. Pancreatic DNA was isolated from pools of R26AID+/KIp48CRE+/KI and control R26AID+/+p48CRE+/KI 20-week-old mice, and then PCR-amplified with specific primers and sequenced as previously described (Perez-Duran et al, 2012). Graphs show cytosine mutation frequency overall (total) or at AGCT hotspots. n = 2. *P-value: Elastase1: 0.0382; Elastase2a: 0.009.",
    "ncbi_link": "AID: 11628
Elastase1: 109901
Elastase2a: 13706
p48: 16391"
  },
  {
    "caption": "C HTM-mediated quantification of γH2AX intensities per nuclei in pancreas explants cultured in vitro for 6 days. Red lines show mean values. Results of two independent experiments are shown. ****P < 0.0001.D Representative images of γH2AX staining in pancreas explants from R26AID+/+p48CRE+/KI (top) or R26AID+/KIp48CRE+/KI mice (bottom) (40× magnification). White arrow points a representative positive cell.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Representative images of Ki67 staining in pancreas from aged (75-week-old) R26AID+/+p48CRE+/KI (top) or R26AID+/KIp48CRE+/KI mice (bottom). Detail is shown on the right. Scale bar: 100 μm. Graph shows quantification of Ki67-positive epithelial cells per mm2 of tissue (n = 8). *P = 0.0266.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Representative immunofluorescence staining of 20-week-old R26AID+/KIp48CRE+/KI mice: blue, DAPI; red, Ki67; green, CK8. Scale bar: 50 μm. Detail is shown on the bottom.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Quantitative FACS analysis of RAE expression in pancreatic explants from R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice. Left: Graph shows mean fluorescence intensity. Each dot represents an individual mouse. n = 9 (R26AID+/+p48CRE+/KI); 8 (R26AID+/KIp48CRE+/KI). P = 0.077. Right: Representative FACS staining for RAE in explants from R26AID+/+p48CRE+/KI (red) and R26AID+/KIp48CRE+/KI mice (black).",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Analysis of RAE expression by ddPCR in aged (75-week-old) mice. Data are presented as the percentage of positive drops normalized to the mean control value. Each point represents an individual mouse and shows the mean amplification from two independent experiments n = 7 (R26AID+/+p48CRE+/KI); 9 (R26AID+/KIp48CRE+/KI). *P = 0.012.",
    "ncbi_link": "RAE: 
AID: 11628
p48: 16391"
  },
  {
    "caption": "Analysis of killing activity. Primary explants of pancreatic cells from R26AID+/+p48CRE+/KI or R26AID+/KIp48CRE+/KI mice were cultured with primary NK cells, and killing activity was assessed as described in Materials and Methods (n = 4). P = 0.19.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Hematoxylin-eosin (HE) staining of pancreas from aged (75-week-old) R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice. Left: Representative HE staining showing an immune infiltrate in a R26AID+/KIp48CRE+/KI mouse. Scale bar: 200 μm. Right: Quantification of number of foci per mm2 of tissue. n = 13 (R26AID+/+p48CRE+/KI); 21 (R26AID+/KIp48CRE+/KI). **P = 0.0098.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "CD3 immunohistochemistry of pancreas from 75-week-old R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice. Left: Representative image of a CD3 infiltrate in a R26AID+/KIp48CRE+/KI mouse. Scale bar: 100 μm. Right: Quantification of the number of CD3-positive cells per mm2 of tissue. n = 12 (R26AID+/+p48CRE+/KI); 13 (R26AID+/KIp48CRE+/KI). *P = 0.0149.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "Representative immunofluorescence staining of CD3 and CD8 in pancreas from 20-week-old R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice. Scale bar: 20 μm.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "TNF-α expression. Total RNA was isolated from pancreas of aged (75-week-old) R26AID+/KIp48CRE+/KI and control mice, and TNF-α expression was quantified by qRT-PCR. Each dot represents an individual mouse. n = 8 (R26AID+/+p48CRE+/KI); 15 (R26AID+/KIp48CRE+/KI). *P = 0.0392.",
    "ncbi_link": "AID: 11628
p48: 16391
TNF-α: 21926"
  },
  {
    "caption": "Cell death detection. Pancreas from 75-week-old R26AID+/+p48CRE+/KI and R26AID+/KIp48CRE+/KI mice were stained with anti-caspase-3. Left: Representative staining from an R26AID+/+p48CRE+/KI mouse (top) and an R26AID+/KIp48CRE+/KI mouse (bottom). Scale bar: 50 μm. Right: Quantification of number of cells per mm2 of tissue. Each dot represents an individual mouse. n = 9 (R26AID+/+p48CRE+/KI); 11 (R26AID+/KIp48CRE+/KI). P = 0.0545.",
    "ncbi_link": "AID: 11628
p48: 16391"
  },
  {
    "caption": "(J and Anti-GFP  signals are grossly similar in 3-6h and 4-6d UAS-myrGFP;  fruGAL4 males (J), n = 6 for each. Data information: Scale bars, 100 μm.",
    "ncbi_link": "GFP: 
fru: 42226
GAL4: 855828"
  },
  {
    "caption": "(A) Wing extension indices  (zero) of isolated 3-6h juvenile w1118/Y; UAS-dTrpA1/+; fruGAL4/+, Met27/Y; UAS-dTrpA1/+; fruGAL4/+ and Gce2.5k/Y; UAS-dTrpA1/+; fruGAL4/+ males at 22 and 27℃. n = 20 for each. (B and C) Wing extension indices (B) and latencies   (C) of isolated 4-6d adult w1118/Y; UAS-dTrpA1/+; fruGAL4/+, Met27/Y; UAS-dTrpA1/+; fruGAL4/+ and Gce2.5k/Y; UAS-dTrpA1/+;  fruGAL4/+ males at 22 and 27℃. n = 20 for each. n.s., not significant, *p < 0.05, ***p < 0.001, Mann-Whitney U test for (B) and unpaired t test for (C). NA, not applicable for latency  analysis. Data information: Error bars indicate SEM.",
    "ncbi_link": "fru: 42226
GAL4: 855828
Gce: 32457
Met: 32114
TrpA1: 39015"
  },
  {
    "caption": "(E and F) Tracking indices of 3-6h and 4-6d w1118/Y; UAS-dTrpA1/+; fruGAL4/+, Met27/Y; UAS-dTrpA1/+; fruGAL4/+ and Gce2.5k/Y; UAS-dTrpA1/+; fruGAL4/+ males toward moving dots at 22 and 27℃. n = 24 for each in (E). n = 22, 20, 24, 24, 24 and 24 from left to right in (F). n.s., not significant, ***p < 0.001, Mann-Whitney U test. Data information: Error bars indicate SEM.",
    "ncbi_link": "fru: 42226
GAL4: 855828
Gce: 32457
Met: 32114
TrpA1: 39015"
  },
  {
    "caption": "(A and B) qPCR  experiments show that Met  (A) and Gce  (B) mRNA levels are significantly knocked down in actin-GAL4>UAS-Met::Gce-IR adult flies. n = 9 for each. ***p<0.001, unpaired t test. Data information: Error bars indicate SEM.",
    "ncbi_link": "actin: 31521
GAL4: 855828
Gce: 32457
Met: 32114"
  },
  {
    "caption": "Courtship behaviors of 3-6h juvenile  and 4-6d adult  males are not significantly affected by knocking down JH receptors Met  and Gce  (UAS-Met::Gce-IR) pan-neuronally  or specifically in neurons  driven by 57C10-GAL4  (C), fruGAL4 (D) N = 22 for each in (C), n = 24 for each in (D) n.s., not significant, Mann-Whitney U test. Data information: Error bars indicate SEM.",
    "ncbi_link": "fru: 42226
GAL4: 855828
Gce: 32457
Met: 32114
57C10: 38196"
  },
  {
    "caption": "Courtship behaviors of 3-6h juvenile  and 4-6d adult  males are not significantly affected by knocking down JH receptors Met  and Gce  (UAS-Met::Gce-IR) pan-neuronally  or specifically in R41A01-GAL4  (E), NPF-GAL4  (F), TH-GAL4  (G) and R71G01-GAL4  (H) respectively. n = 24, 24, 21, and 22 from left to right in (E), n = 24, 24, 24, and 23 from left to right in (F), n = 24, 24, 20 and 24 from left to right in (G) and n = 24, 24, 23 and 24 from left to right in (H). n.s., not significant, Mann-Whitney U test. Data information: Error bars indicate SEM.",
    "ncbi_link": "R41A01: 40940
GAL4: 855828
Gce: 32457
Met: 32114
NPF: 42018
TH: 38746
R71G01: 31469"
  },
  {
    "caption": "(A-D) Expression  pattern of R41A01-GAL4  (pCd, A), NPF-GAL4  (B), TH-GAL4  (C), and R71G01-GAL4  (P1, D) in adult male brains. Representative of three samples for each. Data information: Scale bars, 100 μm.",
    "ncbi_link": "pCd: 40940
R41A01: 40940
GAL4: 855828
NPF: 42018
TH: 38746
P1: 31469
R71G01: 31469"
  },
  {
    "caption": "(I-L) Courtship behaviors of 4-6d adult males  toward virgin females  are similarly intensive and not significantly influenced by activating pCd  (I), NPF  (J), TH  (K) or P1  (L) neurons  at 29℃. n = 24 for each in (I), n = 24, 24, 23, and 23 from left to right in (J), n = 24, 24, 24, and 23 from left to right in (K), and n = 24 for each in (L). n.s., not significant, **p < 0.01, ***p < 0.001, Mann-Whitney U test. Data information: Error bars indicate SEM.",
    "ncbi_link": "pCd: 40940
NPF: 42018
TH: 38746
P1: 31469"
  },
  {
    "caption": "(A and B) Anti-GFP  signals are grossly similar in 3-6h and 4-6d UAS-myrGFP/+; dsxGAL4/+ males (A), which are quantified in (B). n = 6 and 8, respectively. n.s., not significant, Mann-Whitney U test. Data information: Scale bars, 50 μm. Error bars indicate SEM.",
    "ncbi_link": "GFP: 
dsx: 40940
GAL4: 855828"
  },
  {
    "caption": "(E-L) Synaptic  transmission levels are visualized by syb-GRASP   signals (GFP). (E and F) syb-GRASP  signals from NPF neurons  to dsx neurons  are only observed in 4-6d adult  males but not in 3-6h or 1d males (E), which are quantified in (F). The genotype is LexAop-nSyb-spGFP1-10, UAS-CD4-spGFP11/+; NPF-lexA/dsxGal4. n = 12, 7 and 5 from left to right. (G and H) syb-GRASP  signals from dsx neurons   to NPF neurons  in 4-6d adult  males are much stronger than those in 3-6h and 1d males. syb-GRASP  signals in (G) are quantified in (H). The genotype is UAS-nSyb-spGFP1-10, LexAop-CD4-spGFP11/+; NPF-lexA/dsxGal4. n = 13, 7 and 6 from left to right. (I and J) syb-GRASP  signals from TH neurons  to dsx neurons  increase with age  from 3-6h juvenile  males to 4-6d adult  males (I), which are quantified in (J). The genotype is LexAop-nSyb-spGFP1-10, UAS-CD4-spGFP11/TH-LexA; dsxGal4/+. n = 12, 5 and 6, respectively. (K and L) syb-GRASP  signals from dsx neurons  to TH neurons  gradually increase from juvenile  males to adult  males. syb-GRASP  signals in (K) are quantified in (L). The genotype is UAS-nSyb-spGFP1-10, LexAop-CD4-spGFP11/TH-LexA; dsxGal4/+. n = 14, 6 and 6, respectively. White arrowheads indicate syb-GRASP  signals in the same position in brains  of juvenile  males and adult  males. n.s., not significant, **p < 0.01, ***p < 0.001, Mann-Whitney U test. Data information: Scale bars, 50 μm. Error bars indicate SEM.",
    "ncbi_link": "GFP: 
CD4: 920
dsx: 40940
Gal4: 855828
lexA: 948544
LexA: 948544
NPF: 42018
nSyb: 38196
TH: 38746"
  },
  {
    "caption": "(A-D) Activation of NPF neurons  with dTrpA1 induced Ca2+ rise in pC1 dsx neurons  in 4-6d males but not in 3-6h males. (A and B) Ca2+  imaging of pC1 neurons  from 22˚C to 27˚C and 30˚C in 3-6h (A) and 4-6d (B) males. (C) Time-course of fluorescent changes in pC1 neurons  upon activation of NPF neurons  in 3-6h and 4-6d males (UAS-GCaMP6m/LexAop-dTrpA1; NPF-lexA/dsxGAL4), and in 4-6d control males (UAS-GCaMP6m/+; dsxGAL4/+) without NPF neuronal  activation, which are quantified in (D). n = 8 for 4-6d control males, 15 for 3-6h and 8 for 4-6d males with dTrpA1. n.s., not significant, *p < 0.05, **p < 0.01, ***p<0.001, unpaired t test. Data information: Scale bars, 10 μm. Error bars indicate SEM.",
    "ncbi_link": "dsx: 40940
GAL4: 855828
LexA: 948544
lexA: 948544
NPF: 42018
TrpA1: 39015"
  },
  {
    "caption": "(E-H) Activation of TH neurons  with dTrpA1 triggered  Ca2+ increase in pC1 dsx neurons  in both 3-6h and 4-6d males. (E and F) Ca2+ imaging of pC1 neurons  from 22˚C to 27˚C and 30˚C in 3-6h (E) and 4-6d (F) males. (G) Time-course of fluorescent changes in pC1 neurons  upon activation of TH neurons  in 3-6h and 4-6d males (UAS-dTrpA1/LexAop-GCaMP6s; dsxLexA/TH-GAL4), and in 4-6d control males (LexAop-GCaMP6s/+; dsxLexA/+) without activating TH neurons, which are quantified in (H). n = 8 for each. n.s., not significant, *p < 0.05, Mann-Whitney U test. Data information: Scale bars, 10 μm. Error bars indicate SEM.",
    "ncbi_link": "dsx: 40940
GAL4: 855828
LexA: 948544
TH: 38746
TrpA1: 39015"
  },
  {
    "caption": "A. Results of CRISPR screening analyzed by the MAGeCK algorithm.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "B. Wild type (WT) and NCOA4 KO MEFs were pretreated with 25 μg/ml ferric ammonium citrate (FAC) for 16 h and then chased with 20 μg/ml cycloheximide (CHX) for the indicated times. Soluble ferritin expression levels were determined by immunoblotting with the indicated antibodies.",
    "ncbi_link": "NCOA4: 27057"
  },
  {
    "caption": "G. NCOA4 puncta were photobleached in MEFs stably expressing NCOA4-GFP after treatment with 10 μg/ml FAC for 12 h, and then fluorescent recovery was monitored. p62 puncta were photobleached in MEFs stably expressing GFP-human p62, and then fluorescent recovery was monitored. Representative images are shown. Time 0 indicates the start of recovery after photobleaching. Scale bars, 2 μm. H. Quantitative data of fluorescence recovery in (G) shown as means ± SD. 26 dots (NCOA4) or 25 dots (p62) were quantified from three biological replicates.",
    "ncbi_link": "GFP: 
NCOA4: 27057
p62: 8878"
  },
  {
    "caption": "B. NCOA4 KO MEFs reconstituted with NCOA4 variants were treated or not treated with 10 μg/ml FAC for 12 h and then fixed for imaging. Cells were immunostained with anti-myc antibody. Representative images are shown. Scale bar, 10 μm.",
    "ncbi_link": "NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "D. NCOA4 KO MEFs reconstituted with NCOA4 variants were treated or not treated with 10 μg/ml FAC for 12 h, fractionated, and analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "F. Electron micrograph of NCOA4 KO MEFs reconstituted with myc-hNCOA4. Cryosections were labeled with anti-myc antibody. Scale bar, 200nm. G. Quantification of the diameter of NCOA4 condensates. Red line shows the mean. The dot plot represents the diameter of 36 condensates from two biological replicates.",
    "ncbi_link": "myc: 
NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "C. NCOA4 KO MEFs reconstituted with hNCOA4-myc were cultured with 10 μg/ml FAC for the indicated times and fixed for imaging. Cells were immunostained with ferritin and myc antibodies. Scale bar, 10μm.",
    "ncbi_link": "myc: 
NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "E. MEFs expressing hNCOA4-TurboID were treated with 10 μg/ml FAC for 6 h or 24 h and then cultured with DMSO or 50 μM biotin for 30 min. Cells were lysed with Triton buffer, and lysates were pulled down by streptavidin beads. Inputs and pulldown samples were analyzed with immunoblotting by indicated antibodies.",
    "ncbi_link": "TurboID: 
NCOA4: 8031"
  },
  {
    "caption": "G. NCOA4 KO MEFs reconstituted with myc-hNCOA4 were pretreated with 10 μg/ml FAC and then cultured with 20 μg/ml CHX or 200 nM bafilomycin A1 (BafA). Cells were fixed for imaging  and immunostained using myc and LAMP1 antibodies. Scale bar, 10μm.",
    "ncbi_link": "myc: 
NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "A. WT, ATG7 KO, TAX1BP1 KO, and FIP200KO MEFs were treated or not treated with 10 μg/ml FAC for 12 h. Cell lysates were fractionated and analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "ATG7: 74244
FIP200: 12421
TAX1BP1: 52440"
  },
  {
    "caption": "C. HEK293T cells were transfected with GFP-NCOA4 and the indicated FLAG-His-TAX1BP1 variants. Soluble lysates extracted from transfected cells were immunoprecipitated with anti-FLAG antibody. Inputs and immunoprecipitated samples were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "FLAG: 
GFP: 
His: 
NCOA4: 8031
TAX1BP1: 8887"
  },
  {
    "caption": "WT MEFs and TAX1BP1 KO MEFs reconstituted with the indicated TAX1BP1 variants were untreated or treated with 10 μg/ml FAC for 12 h. (D, F) Cell lysates were fractionated and analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "TAX1BP1: 52440
TAX1BP1: 8887"
  },
  {
    "caption": "WT MEFs  and  TAX1BP1  KO MEFs  reconstituted with the indicated TAX1BP1 variants were treated with 10 μg/ml  FAC for 12 h. (E) Cells were fixed for imaging  and immunostained  to analyze ferritin localization. Scale bar, 10μm.",
    "ncbi_link": "TAX1BP1: 52440
TAX1BP1: 8887"
  },
  {
    "caption": "C. WT and TAX1BP1 KO MEFs were pretreated with 25 μg/ml FAC for 16 h and then cultured with 100 μM Dfo. Lysates  were fractionated and then analyzed by immunoblotting with the indicated antibodies. D. Soluble FTL bands in (C) were quantified by densitometry. Data are shown as the means ± SD of three biological replicates.",
    "ncbi_link": "TAX1BP1: 52440"
  },
  {
    "caption": "E. TAX1BP1 KO MEFs (sg1 clone) stably expressing FLAG-OsTIR1 (F74G) and FLAG-mAID-mTAX1BP1  were pretreated with 10 μg/ml FAC for 12 h, cultured with DMSO or 1 μM  5-Ph-IAA for 2 h, and then treated with 100 μM Dfo. Soluble lysates were analyzed by immunoblotting with the indicated antibodies. 5-Ph-IAA, a derivative of Auxin; mAID, mini auxin-inducible degron",
    "ncbi_link": "FLAG: 
TIR1: 4337827
TAX1BP1: 52440"
  },
  {
    "caption": "F. TAX1BP1 KO MEFs (clone sg1) in which ATG7 was knocked down were pretreated with 10 μg/ml FAC for 12 h and then cultured with 100 μM Dfo. Soluble lysates were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "ATG7: 74244
TAX1BP1: 52440"
  },
  {
    "caption": "G. TAX1BP1 KO MEFs (clone sg1) stably expressing myc-hNCOA4 pretreated with 25 μg/ml FAC for 16 h were cultured with 100 μM Dfo, and soluble lysates were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "myc: 
NCOA4: 8031
TAX1BP1: 52440"
  },
  {
    "caption": "H, I. NCOA4 KO MEFs reconstituted with NCOA4 variants were pretreated with 10 μg/ml FAC for 12 h and then chased with (H) 20 μg/ml CHX or (I) 100 μM Dfo for the indicated times. Soluble lysates were analyzed by immunoblotting with the indicated antibodies.",
    "ncbi_link": "NCOA4: 27057
NCOA4: 8031"
  },
  {
    "caption": "J. MEFs expressing hNCOA4-TurboID  were treated with 10 μg/ml FAC for 3 h (indicated as F) or 100 μM DFO for 3 h after treatment with 10 μg/ml FAC for 12 h (indicated as D), and then cultured with DMSO or 50 μM biotin for 30 min. Triton-soluble cell lysates were pulled down by streptavidin beads. Inputs and pulldown samples were analyzed by immunoblotting with the indicated antibodies. The black and white arrowheads indicate hNCOA4-TurboID and endogenous  NCOA4, respectively.",
    "ncbi_link": "TurboID: 
NCOA4: 8031"
  },
  {
    "caption": "(A) Western blot analysis of whole head homogenates from transgenic flies expressing a Myc-tagged PINK1 genomic construct and a UAS-RNAi construct driven by elav-GAL4. The RNAi constructs used were as follows: the non-specific control mCherry-RNAi (Control-R), Lon-RNAi1 (Lon-R1), and Lon-RNAi2 (Lon-R2). An anti-Myc antibody was used to detect PINK1 and an anti-Actin antibody was used as a protein loading control. (B) Densitometry of the PINK1-Myc bands from the indicated genotypes was performed using Fiji software. The PINK1-Myc band intensities were then normalized to their respective Actin loading controls, and these ratios were in turn normalized to the Control-R PINK1/Actin ratio.",
    "ncbi_link": "GAL4: 
UAS: 
Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "(C) Western blot analysis of Lon protease (Lon), Mitochondrial transcription factor A (TFAM), Heat shock protein 60 (Hsp60) and Actin in whole head homogenate from control and Lon deficient animals. (D) Quantification of the Lon band intensities from the indicated genotypes performed as described in B. (E) Quantification of the TFAM bands from the indicated genotypes performed as described in B. (F) Quantification of the Hsp60 bands from the indicated genotypes performed as described in B.",
    "ncbi_link": "Lon: 40138"
  },
  {
    "caption": "PINK1 accumulates in the mitochondrial and postmitochondrial supernatant fractions upon knockdown of Lon.(A) Mitochondrial (Mito) and postmitochondrial supernatant (Sup) protein fractions isolated from the heads of flies of the indicated genotypes were analyzed by western blot with antibodies to Myc, Complex V β (Comp V β), NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), voltage-dependent anion channel (VDAC) and Actin. elav-GAL4 was used to drive expression of the RNAi constructs used in these experiments. (B) Densitometry of the MPP-PINK1 bands in the mitochondrial fractions from the indicated genotypes was performed using Fiji software. PINK1 band intensities were normalized to VDAC intensity, and this ratio was in turn normalized to the MPP-PINK1/VDAC ratio in Control-R animals. (C) Quantification of the Rho-PINK1 band intensities in mitochondrial fractions from the indicated genotypes was performed as described in B. (D) Quantification of the AFG-PINK1 band intensities in mitochondrial fractions from the indicated genotypes was performed as described in B. (E) Quantification of the MPP-PINK1 band intensities in the supernatant fractions from the indicated genotypes was performed as described in B except that Actin rather than VDAC was used as the loading control. (F) Quantification of the Rho-PINK1 band intensities in supernatant fractions from the indicated genotypes was performed as described in E. (G) Quantification of the AFG-PINK1 band intensities in supernatant fractions from the indicated genotypes was performed as described in E. Results shown are representative of at least three independent subcellular fractionation experiments per genotype. Error bars represent s.e.m. *p<0.05 by Student t test.",
    "ncbi_link": "GAL4: 
Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "A) Mitochondrial fractions isolated from the heads of flies expressing Control-R were divided in half. One of the two samples was treated with 0.5 µg/ml Proteinase K and both samples were incubated at 4°C for 20 minutes. Samples were then subjected to western blot analysis using antibodies to the outer membrane protein Mitofusin (Mfn), the inner membrane-associated matrix protein Complex V β (Comp V β), and the matrix luminal protein pyruvate dehydrogenase (PDH). elav-GAL4 was used to drive expression of all the RNAi constructs used in this and the following experiments. (B) Densitometry of Mfn, Comp V β, and PDH bands from experiments represented by panel A were performed using Fiji software, and the ratios of the band intensities in the sample containing ProK to the sample lacking ProK are shown.",
    "ncbi_link": "GAL4: "
  },
  {
    "caption": "(C) Mitochondrial fractions isolated from the heads of flies expressing Control-R and PINK1-Myc were divided in half. Each sample was treated with the indicated concentrations of ProK. Following incubation, samples were subjected to western blot analysis using antibodies to the indicated proteins. (D) Densitometry of the PINK1-Myc, Comp V β, and PDH bands from experiments represented by panel C were performed as described in B. The Mfn quantification data from panel B is also included for comparison.",
    "ncbi_link": "PINK1: 31607"
  },
  {
    "caption": "(E) Mitochondrial fractions isolated from the heads of Lon-R2 and PINK1-Myc expressing flies were divided in half. Each sample was treated with the indicated concentrations of ProK. Following incubation, samples were subjected to western blot analysis using antibodies to the indicated proteins. (F) Densitometry of the PINK1-Myc, Comp V β, and PDH bands from experiments represented by panel E were performed as described in B. All experiments described were repeated at least three times. Error bars represent s.e.m.",
    "ncbi_link": "Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "PINK1 accumulates in the mitochondrialmatrix upon knockdown of Lon.Immunofluorescent staining of thoracic muscles expressing matrix-targeted YFP (Mito-YFP) under control of the sqh genomic promoter, together with either (A) Myc-tagged MitochondrialRho (Miro-Myc), (B) FLAG-tagged Optic atrophy 1 (Opa1-FLAG), (C) endogenous Cytochrome C (Cyto C), (D) Myc-tagged PINK1 (PINK1-Myc), or (E) Lon-RNAi1 (Lon-R1) and PINK1-Myc. The muscle-specific Mhc-GAL4 driver was used to drive expression of Miro-Myc in panel A and Opa1-FLAG in panel B, and the muscle-specific Dmef2-GAL4 driver was used to drive expression of Lon-R1 in panel E. (F) We determined the percent volume shared between green objects (representing the matrix marker Mito-YFP) and red objects (representing the mitochondrial proteins analyzed in A-E). Red objects that shared at least 60% of their volume with Mito-YFP were considered to co-localize. Bar represents 2 µm.",
    "ncbi_link": "Dmef2: 
GAL4: 
Mhc: 
sqh: 
Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "A) The eye severity score of flies co-overexpressing PINK1 with Control-R (n = 74), Lon-R1 (n = 163), or Lon-R2 (n = 90) using the ey-GAL4 driver.",
    "ncbi_link": "GAL4: 
Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "(B) Comparison of the frequency of thoracic indentations in flies expressing the PINK1-RNAi construct (PINK1-R) in an otherwise wild-type background to the frequency in animals that also bear heterozygous mutations in Lon: PINK1-RNAi +/+ (n = 306), PINK1-RNAi LonEP/+ (n = 74), and PINK1-RNAi LonDf/+ (n = 83). LonEP refers to the LonG3998 P-element allele of Lon, and LonDf refers to the Df(3L)Exel9011 deletion that removes the Lon gene along with several other genes. The Dmef2-GAL4 driver was used to drive expression of the PINK1-R construct in experiments described in panel B. Error bars represent s.e.m. *p<0.05, **p<0.005 by Student t test.",
    "ncbi_link": "Dmef2: 
GAL4: 
Lon: 40138
PINK1: 31607"
  },
  {
    "caption": "C Co-immunoprecipitation of XIAP and endogenous USP9X in HEK 293T cells that were transfected with FLAG-tagged XIAP or empty vector (EV) and synchronized in mitosis using nocodazole or left untreated.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "D Co-immunoprecipitation of XIAP and endogenous USP9X in HEK 293T cells that were treated as in (C), but with additional transfection of the FLAG-tagged XIAP single amino acid mutants G188R and G188E. Only mitotic samples are shown. The asterisk denotes ubiquitylated forms of XIAP.",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "F Immunoblot analysis of NIH 3T3 cells that were transfected with expression constructs for USP9XWT or the catalytically inactive mutant USP9XC1556S. The band in the EV control lane of the anti-V5 panel marks an unspecific band produced by the antibody.",
    "ncbi_link": "USP9X: 22284"
  },
  {
    "caption": "A Immunoblot analysis of WT, Xiap-/-, Mcl1-/- or cIap2-/- mouse embryonic fibroblasts that were lentivirally infected with shRNA constructs directed against a non-relevant mRNA (Ctrl) or against Usp9X mRNA and treated with taxol as specified.",
    "ncbi_link": "cIap2: 11797
Mcl1: 17210
Usp9X: 22284
Xiap: 11798"
  },
  {
    "caption": "B Two-dimensional cell-cycle analysis (BrdU/PI) of cells described in (A). Sub G1 and G2/M fractions of cells were quantified and averaged with two additional, independent experiments (n=3, ± SD; WT: **, P = 0.0016; ***, P = 0.0004; Mcl1-/-: ***, P = 0.0003; **, P = 0.0017; cIap2-/-: **, P = 0.0043, Student's t test). Black bars exemplify shRNA Ctrl, white bars shRNA Usp9X samples.",
    "ncbi_link": "Usp9X: 22284"
  },
  {
    "caption": "C Immunoblot analysis of HeLa cells transfected with a FLAG-tagged USP9X expression construct or empty vector (EV) and treated with taxol for the indicated times.",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "D Immunoblot analysis of HeLa cells that were transfected with a FLAG-tagged XIAP expression construct or empty vector and treated as in (C).",
    "ncbi_link": "XIAP: 331"
  },
  {
    "caption": "F Immunoblot analysis of HeLa cells that were transfected with siRNA oligonucleotides directed against a non-relevant mRNA (Ctrl) or against Xiap mRNA and treated with taxol as specified.",
    "ncbi_link": "Xiap: 331"
  },
  {
    "caption": "B Kaplan Meier survival curves of mice that were injected intravenously with syngeneic Eμ-Myc lymphoma cells transduced with the indicated shRNA constructs as described in (A). Prior to injection, cells were sorted for viability (propidium iodide negative) and GFP positivity (sh_Ctrl, black, n = 6; sh_USP9X, gray, n = 5). *P = 0.0293; Mantel-Cox test.",
    "ncbi_link": "USP9X: 22284"
  },
  {
    "caption": "C Kaplan-Meier survival curves of mice that were injected with syngeneic Eμ-Myc lymphoma cells transduced with the indicated shRNA constructs as described in (A) and treated as in (B) (sh_Ctrl, black, n = 6; sh_XIAP, gray, n = 6). **, P = 0.0020; Mantel-Cox test.",
    "ncbi_link": "XIAP: 11798"
  },
  {
    "caption": "H Mean change in standardized 18FDG uptake of ROI between pre and post treatment imaging corrected for initial tumor burden (sh_Ctrl, black, n=6; sh_Usp9X, white, n=8; sh_Xiap, grey, n=8). Within the sh_Usp9X and sh_Xiap groups all animals lived up to control imaging, while two of eight animals of the sh_ctrl group had to be sacrificed prematurely because they had reached the predefined criteria of maximum tumor burden. These animals had to be excluded from final analysis, suggesting an underestimation of the actual effect. Data was obtained from two independent experiments. ****, P < 0.0001; *, P = 0.0167, student's t-test",
    "ncbi_link": "Usp9X: 22284
Xiap: 11798"
  },
  {
    "caption": "B FACS analysis (propidium iodide (PI)) of USP9X high and low expressing DLBCL cells shown in (A) to determine cell survival. Cells were treated with taxol and collected at the specified time points. PI negative cells are indicated relative to time point 0 (n=3 ± SD).",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "C Immunoblot analyses of the indicated DLBCL cell lines that were lentivirally transduced with IRES-GFP shRNA constructs against USP9X or a non-relevant mRNA, FACS sorted for GFP+ PI- cells and exposed to taxol for the indicated periods of time. The quantification of cleaved caspase 3 (CC3) at the 24 hr post taxol treatment timepoint from four independent experiments is quantified in the graph on the right side and normalized to control shRNA. **, P = 0.0099, student's t-test",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "F Collective assessment of USP9X and XIAP expression determined by immunohistochemistry in tissue microarrays (TMA) derived from a patient cohort representing 121 evaluable human CD20+ aggressive B-cell lymphomas. High USP9X expression was identified in 37 cases (31 %) and significantly correlated with high XIAP expression levels (**, P = 0.004; Student's t test).",
    "ncbi_link": "USP9X: 8239"
  },
  {
    "caption": "G Expression data derived from (E) was correlated with clinical follow-up. Within a cohort of 58 patients receiving vincristine-containing chemotherapy (CHOP regimen: cyclophosphamide, doxorubicin, vincristine, prednisone) without the addition of the anti-CD20 antibody rituximab (left panel) overexpression of USP9X and XIAP (n = 14, straight line) was associated with a significantly shortened event-free survival (EFS) as compared to all remaining patients (n = 44, dotted line) (*, P = 0.050; log rank test). Within a cohort of 63 patients receiving the CHOP regimen with addition of the anti-CD20 antibody rituximab overexpression of USP9X and XIAP (n = 14, straight line) was not associated with a shortened event-free survival (EFS) as compared to all remaining patients (n = 49, dotted line) (P = 0.454).",
    "ncbi_link": "USP9X: 8239
XIAP: 331"
  },
  {
    "caption": "(left) Luciferase expression in HEK293 cells driven by deletion constructs of POLG proximal promoter. (right) Luciferase expression with mutated CAAT-boxes in POLG promoter. The error bars indicate standard deviation in 3 biological replicates. AU; arbitrary units.",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "Expression pattern driven by 500 bp Polg proximal promoter in E12.5 mouse embryo. LacZ-positive cell populations in the developing midbrain (black arrows), dorsal root ganglia (grey arrows) and motoneuron progenitors (arrowhead) of the neural tube. Somites show some expression (white arrow). Sectioning planes indicated by red lines. Scale bars 100 µm.",
    "ncbi_link": "Polg: 5428"
  },
  {
    "caption": "- (G) POLG enhancer elements are functional in vivo and drive expression in E12.5 transgenic mice. Sectioning planes indicated by red lines. Black line in (E) marks the expression in the dorsal neural tube, whereas rostral and caudal regions lack dorsal expression (black arrows).",
    "ncbi_link": "POLG: 5428"
  },
  {
    "caption": "Adult mouse spinal cord, EE2 and (D) EE3 expression pattern. Dorsal horns, laminae I-III (black arrows) and central canal (arrowheads). LacZ staining. Dashed lines in (C) indicates the region of dorsal horn shown in (D), (F) and (G). Inlets in (C) and (E) show POLG immunohistochemistry of dorsal horn and central canal (grey arrow), respectively. Scale bars: 100 µm if not indicated otherwise.",
    "ncbi_link": "POLG: 18975"
  },
  {
    "caption": "The number of distal DNAse I hypersensitive sites (DHSs) of mtDNA maintenance genes and genes in the genomic POLG locus correlating >0.85 with target promoter DHS across 125 cell lines. Abbreviations: TWNK, Twinkle protein; POLG, DNA Polymerase gamma, catalytic subunit; POLG2, DNA Polymerase gamma, accessory subunit; SSBP1, Single stranded DNA binding protein 1; TFAM, mitochondrial transcription factor A; FANCI, Fanconi anemia group I protein; RHCG, Ammonium transporter Rh type C; TICRR, Treslin.",
    "ncbi_link": "POLG: 
FANCI: 55215
POLG: 5428
POLG2: 11232
RHCG: 51458
SSBP1: 6742
TFAM: 7019
TICRR: 90381
TWNK: 56652"
  },
  {
    "caption": "Genomic distribution of POLG DHSs. Black arrow shows a cluster upstream from POLG coding region.",
    "ncbi_link": "POLG: 
POLG: 5428"
  },
  {
    "caption": "Expression of LINC00925 and POLG in different human tissues and cell types. Quantitative PCR amplification of cDNA. Abbreviations: iPS, induced pluripotent stem cell; SH5Y, neuroblastoma line; HepG2, liver hepatocellular carcinoma line; U2OS bone osteosarcoma line. Error bars indicate standard deviation in 3 technical replicates. AU; arbitrary units.",
    "ncbi_link": "LINC00925: 254559
POLG: 5428"
  },
  {
    "caption": "Polg and long-non-coding RNA Ai854517 (mouse homologue of human LINC00925) correlate tightly in mouse cerebellar development. Time points: E18, postnatal days 0, 3, 6, 9; three mice per time point. Expression calculated as cap analysis of gene expression (CAGE) hits in the transcription start site (CTSS).",
    "ncbi_link": "Ai854517: 101694
Polg: 18975"
  },
  {
    "caption": "Ai854517 and Polg transcripts colocalize in adult mouse brain; in situ hybridization. HC, hippocampus; cerebellar molecular layer (M), Purkinje cell layer (PC), granular cell layer (GC). Scale bars: hippocampus 760 µm, cerebellum 300 µm.",
    "ncbi_link": "Ai854517: 101694
Polg: 18975"
  },
  {
    "caption": "Expression levels of MIR9-3 and Ai854517 correlate in mouse cerebellar development. Time points: E18, postnatal day 0, 3, 6, 9; three mice per time point.. Expression calculated as cap analysis of gene expression (CAGE) hits in the transcription start site (CTSS).",
    "ncbi_link": "MIR9-3: 723968
Ai854517: 101694"
  },
  {
    "caption": "RNA expressions of MIR9, NR2E2, LDLDRAP1 and MTHFD2 in HEK293 untransfected controls and in cells transfected with pre-MIR9 or scrambled RNA. Shown is mean with standard error of the mean. Statistical testing was performed using 1-way ANOVA with Dunnet's correction for multiple comparisons. Abbreviations: AU; arbitrary units.",
    "ncbi_link": "NR2E2: 84868
LDLDRAP1: 26119
MIR9: 407047///407046///407051
MTHFD2: 10797"
  },
  {
    "caption": "A. KD efficiency of three different Syt11 shRNAs in DRG neurons. Cultured DRG neurons were infected with control or shRNA-expressing lentiviruses at DIV 1, and Western blotting for Syt11, Syt1, Syt4, synaptobrevin 2 (Syb2), SNAP25, complexin 1/2 (Cpx1, Cpx2), clathrin, adaptor protein 2 (AP-2), and β-actin were performed at DIV 6-7. N = 4 independent experiments.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "B, C. Representative Cm traces induced by 200-ms pulse depolarization (arrows) ib DRG neurons. DRG neurons were transfected with plasmids expressing shSyt11-2 (Syt11 KD, KD) or scrambled shRNA (Sc) and Cm recording was performed 5 days after transfection. Endo-5s represents the Cm decay 5 s after stimulation. Insets show Ca2+ currents recorded in the same neurons.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "D. Representative Cm overshoot recorded from an Syt11 KD neuron. About 45% of the KD neurons showed excessive membrane retrieval after a 200-ms depolarizing pulse.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "E. Averaged Cm traces recorded from Control (Ctrl), Sc, KD (from all three shRNAs, n = 39 for shSyt11-2, n = 7 for shSyt11-1, n = 14 for shSyt11-3), and rescued (with the shSyt11-2-resistant form of Syt11) DRG neurons.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "G. FM1-43 uptake by Syt11 KD (RFP-positive) and control (RFP-negative) hippocampal neurons stimulated by 100 mM K+ for 2 min. Quantitative data are shown in the lower-right panel. Scale bars, 20 μm.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "I. Time-course of FM4-64 unloading from control, Syt11 KD, and rescued nerve terminals within the same field of view (6 coverslips from at least 3 biological repeats each).",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "A. DRG neurons expressing Myc-Syt11 were immunostained for Myc-Syt11, dynamin (Dyn), AP-2, clathrin (CL), TGN46, synaptobrevin 2 (Syb2), and LAMP1. For dynamin, the box along the plasma membrane was straightened, enlarged, and is shown in the upper right panels with arrows indicating co-localized puncta. An enlarged inset of the inside of the cell (box) is shown in the lower panel. For localization of the transferrin receptor, EGFP-transferrin receptor (TfR) was expressed in DRG neurons. Scale bars, 10 μm.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "A. Transferrin (Tf, red) uptake in Syt11 KD (GFP-positive) and control neurons. Quantitative data are on the right. Scale bars, 20 μm.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "B. Tf uptake in Syt11 over-expressing and control neurons. Quantitative data are on the right. Scale bars, 20 μm.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "C. Normalized ∆Cm induced by 200-ms depolarization of a Syt11 KD neuron in the presence of 100 μM MDC was fitted to a double-exponential decay function (solid black and red, fitted curves).",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "D. Fast and slow time-constants of endocytosis in Syt11 KD neurons recorded as in (C).",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "G, H. Representative z-projected fluorescence images and statistics showing the large dextran uptake in Syt11 KD and control DRG neurons. Neurons were loaded with 50 μM tetramethylrhodamine-dextran (40 kD) by 2-min exposure to 100 mM KCl. Scale bars, 10 μm.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "D, E. Diameters of SVs and DCVs in Syt11 KD and control neurons with (100K, statistics from 6 control cells and 9 KD cells) or without 100 mM K+ stimulation (SE, statistics from 6 cells for each group).",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "Figure 9. Functional domains of Syt11 in endocytosisA. Diagram of the mutant forms of Syt11 used for rescue experiments.B-D. Statistics of FM4-64 (5 min), Tf, and large dextran (40-KD) uptake into KD neurons with or without rescue by indicated forms of Syt11.All data are presented as mean ± s.e.m. of 3 independent experiments. One-way ANOVA, values labeled with different letters (a, b, and c) are significantly different from each other, ***P < 0.001. Student's t-test for the comparison between KD and control cells in (B-D), **P < 0.01, ***P < 0.001.",
    "ncbi_link": "Syt11: 60568"
  },
  {
    "caption": "Western blotting in the WT, Trim71 knockout (Trim71_KO), and the Trim71 mutant (R783H) mESCs. The signals from the pluripotency factors Nanog and Oct4 were obtained through short (~10 seconds) exposure.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Distribution of the WT Trim71 and the R783H Trim71 mutant binding regions in the mouse genome. In each CLIP-seq, there are two biological replicates. The binding regions present in both of the biological replicates are used for the analysis.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "CLIP-qRT-PCR for the identified target mRNAs of the Trim71 mutant R783H. The results represent the means (±SD) of three independent experiments.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "UCSC genome browser snapshot for the CLIP-seq data from Trim71 and the Trim71 mutant R783H in the Lsd1 locus. The red box indicates the binding region of the Trim71 mutant R783H. The inputs are from the size-matched input samples in the CLIP-seq analysis.",
    "ncbi_link": "Lsd1: 99982
Trim71: 636931"
  },
  {
    "caption": "B. A representative set of Western blots in the WT and the R783H Trim71 mESCs. C. Quantification of the target proteins in the WT and the R783H Trim71 mESCs. Data information: The results represent the means (± SD) of three independent experiments. One-Way ANOVA was used to determine the significance of the difference, *p<0.05. The Western blots listed in B is the Biological Replicate 1",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Western blotting in the WT and the Trim71 (R783H) mESCs.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Polysome analysis in the WT and the Trim71 (R783H) mESCs.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Quantification of the indicated mRNA distribution in the RNP, 80S, and polysome fractions from the WT and the Trim71 (R783H) mESCs.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Western blotting in the WT mESCs expressing an empty vector, Flag-Trim71, Flag-Trim71(R783H).",
    "ncbi_link": "Flag: 
Trim71: 636931"
  },
  {
    "caption": "Quantification of Lsd1 protein and mRNA in the WT mESCs expressing an empty vector, Flag-Trim71, Flag-Trim71(R783H).",
    "ncbi_link": "Flag: 
Trim71: 636931"
  },
  {
    "caption": "Polysome analysis in the WT mESCs expressing an empty vector, Flag-Trim71, Flag-Trim71(R783H). Quantification of the indicated mRNA distribution in the RNP, 80S, and polysome fractions from the WT mESCs expressing an empty vector, Flag-Trim71, Flag-Trim71(R783H).",
    "ncbi_link": "Flag: 
Trim71: 636931"
  },
  {
    "caption": "Deletion of the Trim71 mutant R783H binding site in Lsd1 mRNA's 3'UTR.",
    "ncbi_link": "Lsd1: 99982
Trim71: 636931"
  },
  {
    "caption": "CLIP-RIP followed by qRT-PCR to examine mRNAs associated with the Trim71 and the Trim71 mutant R783H in the WT, Trim71(R783H), CLIP∆, and Trim71(R783H)/CLIP∆ mESCs. The mRNA signals from the E14 mESCs were set as 1 for relative comparison.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Western blotting in the WT, Trim71(R783H), CLIP∆, and Trim71(R783H)/CLIP∆ mESCs.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Quantification of Lsd1 protein and mRNA in the WT, Trim71(R783H), CLIP∆, and Trim71(R783H)/CLIP∆ mESCs. Beta-Tubulin and 18S rRNA were used for normalization in the protein and mRNA quantification, respectively.",
    "ncbi_link": "Trim71: 636931"
  },
  {
    "caption": "Western blotting in the WT and the Trim71(R783H) mESCs with dox-inducible expression of Lsd1-GFP.",
    "ncbi_link": "GFP: 
Lsd1: 99982
Trim71: 636931"
  },
  {
    "caption": "Western blotting in the WT and the R783H/+ mESCs with dox-inducible expression of Lsd1-GFP.",
    "ncbi_link": "GFP: 
Lsd1: 99982"
  },
  {
    "caption": "Exit pluripotency assay for the WT and the R783H/+ mESCs with dox-inducible expression of Lsd1-GFP.",
    "ncbi_link": "GFP: 
Lsd1: 99982"
  },
  {
    "caption": "Representative Western blotting and quantification of pluripotency factors during the differentiation of the WT and the R783H/+ mESCs with dox-inducible expression of Lsd1-GFP.",
    "ncbi_link": "GFP: 
Lsd1: 99982"
  },
  {
    "caption": "Representative Western blotting and quantification of neural lineage markers during the neural differentiation of the WT and the R783H/+ mESCs with dox-inducible expression of Lsd1-GFP.",
    "ncbi_link": "GFP: 
Lsd1: 99982"
  },
  {
    "caption": "Lysis  of different target cells in co-culture with NK  cells was quantified in various  cytotoxicity assays. (B) Left panel: Representative contour plots showing the percentage of  .221-DR4/5KO (control) and .221-Cas9  cells (target) in the presence or absence of NK  cells. Middle panel: Ratio between .221-DR4/5KO and .221-Cas9  cells (y-axis) in the presence or absence of NK  cells. Right panel: Specific lysis  of .221-Cas9  cells displayed as % (n = 12 different donors). Each data point represents the mean of at least 3 technical replicates. Data information: Wilcoxon signed-rank test. Experiments were performed in four batches with three different donors each. \"No NK\" control samples served as a reference for all donors in each batch. Lines connect each data value of the NK  cell condition with their designated \"No NK\" control. Box plots represent the median and 25%/75% percentile. Whiskers indicate minimum and maximum data points.",
    "ncbi_link": "Cas9: 69900935
DR4: 8797"
  },
  {
    "caption": "(A-B) qRT-PCR analysis of TGF ligands, TGF receptors, and TGF target expression in control and FRS2 knockdown HASMCs. (NS: not significant compared to control, *p<0.05; **p<0.01; ***p<0.001 compared to control; unpaired two-tailed Student's t test). -actin was used for sample loading normalization. Histogram of qRT-PCR results are representative of three independent experiments.",
    "ncbi_link": "actin: 
FRS2: 10818"
  },
  {
    "caption": "(C) Left: Immunoblot analysis of TGFRs, phosphorylated Smad2 (p-Smad2), and phosphorylated Smad3 (p-Smad3) in control and FRS2 knockdown HASMCs. Blots are representative of four independent experiments. Right: Band intensities of p-Smad2, p-Smad3, TGFR1, and TGFR2 were normalized to Smad2/3 or GAPDH and expressed as a fraction of a control value. Results are expressed as means ± SD (*p<0.05; ***p<0.001 compared to control; unpaired two-tailed Student's t test).",
    "ncbi_link": "FRS2: 10818"
  },
  {
    "caption": "(A) Left: Immunoblot analysis of smooth muscle marker gene expression in control and FRS2 knockdown HASMCs. Blots are representative of four independent experiments. Right: Band intensities of SM -actin, SM22, and SM-calponin were normalized to -tubulin and expressed as a fraction of a control value. Results are expressed as means ± SD (**p<0.01; ***p<0.001 compared to control; unpaired two-tailed Student's t test).",
    "ncbi_link": "FRS2: 10818"
  },
  {
    "caption": "(B) qRT-PCR analysis of SMC transcription factor gene expression in control and FRS2 knockdown HASMCs. (*p<0.05; **p<0.01; ***p<0.001 compared to control; unpaired two-tailed Student's t test. N=3). -actin was used for sample loading normalization.",
    "ncbi_link": "actin: 
FRS2: 10818"
  },
  {
    "caption": "(C) Collagen gel contraction assays were used to determine the contractile ability of control or FRS2 knockdown HASMCs (*p<0.05 compared to control; unpaired two-tailed Student's t test. N=3).",
    "ncbi_link": "FRS2: 10818"
  },
  {
    "caption": "(D-F) Upper panels: Immunoblots of smooth muscle markers, phosphorylated Smad2 (p-Smad2), and TGFR1 expression in control and FRS2 knockdown HASMCs treated with SB431542 (10 m), TGFR2 or Smad2 shRNA lentiviruses. Blots are representative of three independent experiments. Bottom panels: Band intensities of SM-calponin and p-Smad2 were normalized to -tubulin, HSP90, or Smad2 and expressed as a fraction of a control value.",
    "ncbi_link": "FRS2: 10818
Smad2: 4087
TGFR2: 7048"
  },
  {
    "caption": "(A) Quantitative real-time PCR analysis of mature let-7 family in control and FRS2 knockdown HASMCs. SNORD47 was used to normalize the variability in template loading. Histogram of qRT-PCR results are three independent experiments.",
    "ncbi_link": "FRS2: 10818
let-7: RF00027
SNORD47: 26802"
  },
  {
    "caption": "(B) Upper panel: Immunoblots of SM-calponin, phosphorylated Smad2 (p-Smad2), and TGFR1 expression in control and FRS2 knockdown HASMCs transduced with or without let-7b lentiviruses. Blots are representative of three independent experiments. Bottom panels: Band intensities of SM-calponin and p-Smad2 were normalized to GAPDH or Smad2 and expressed as a fraction of a control value.",
    "ncbi_link": "FRS2: 10818
let-7: RF00027"
  },
  {
    "caption": "(D) HASMCs were cultured in the growth medium (M231 + SMGS) at day 0 then switched from growth conditions to differentiation medium (M231 + SMDS) for 8 days. Quantitative real-time PCR analysis of mature let-7 family in HASMCs. SNORD47 was used to normalize the variability in template loading. Histogram of qRT-PCR results are three independent experiments.",
    "ncbi_link": "let-7: RF00027
SNORD47: 26802"
  },
  {
    "caption": "(E) Control and FRS2 knockdown HASMCs were cultured in the growth medium (M231 + SMGS) at day 0 then switched from growth conditions to differentiation medium (M231 + SMDS) for 6 days with or without let-7b lentiviruses. Immunoblots of smooth muscle markers, phosphorylated Smad2 (p-Smad2), and TGFR1 expression in control and FRS2 knockdown HASMCs with or without let-7b lentiviruses. Blots are representative of three independent experiments.",
    "ncbi_link": "FRS2: 10818
let-7: RF00027"
  },
  {
    "caption": "(A) Dissected mouse aorta demonstrating lipid-rich plaques in brachiocephalic artery after 4 months of high fat diet compared to the normal diet in Apoe-/- mice. (b) & (d) Cross-section of brachiocephalic artery from (a) & (c) stained with Oil Red O. L: lumen. Scale bar: 4 mm. 3 mice per group.",
    "ncbi_link": "Apoe: 11816"
  },
  {
    "caption": "(C-F) Analysis of brachiocephalic artery of Apoe-/- mice maintained for 4 months on either normal or high fat diet using anti-CD31 (green), anti-p-FGFR1 (red), anti-FGFR1 (red), anti-p-Smad2 (red), and anti-p-Smad3 (red) antibodies. Nuclei counterstained with DAPI (blue). Scale bar: 62 m. L: lumen. M: Media. 6 mice per group.",
    "ncbi_link": "Apoe: 11816"
  },
  {
    "caption": "(A) Representative photomicrographs of Oil Red O-stained atherosclerotic lesions in the aortic arch, of Apoe-/- or Frs2SMCKO/Apoe-/- mice after 16 weeks of high fat diet. 3 mice per group. Scale bar: 5 mm.",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(B) (Left) Microphotographs of aortas (en face) from Apoe-/- and Frs2SMCKO/Apoe-/- mice after 16 weeks of high fat diet after staining with Oil Red O. (Right) Lesion area quantification. All data shown as mean ± SD. (***p<0.001 compared to Apoe-/-; unpaired two-tailed Student's t test). 12 mice per group.",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(C-D) Representative cross-sections of brachiocephalic arteries Apoe-/- and Frs2SMCKO/Apoe-/- mice stained with hematoxylin and eosin (H&E) (C) and Movat (D). (b)&(d) are high-magnification view from (a)&(c). NC: necrotic core. Apoe-/- mice N=9, Frs2SMCKO/Apoe-/- mice N=12.",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(E) Histological analysis of atheosclerotic plaque with anti-Ki67 antibody. Nuclei were counterstained with DAPI (blue). (b)&(d) are high-magnification images from (a)&(c). Scale bar: 62 m (low-magnification images); 10 m (high-magnification images). Apoe-/- mice N=9, Frs2SMCKO/Apoe-/- mice N=12.",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(F) Quantification of plaque cellularity; Apoe-/- mice N=9, Frs2SMCKO/Apoe-/- mice N=12 (***p<0.001 compared to Apoe-/-; unpaired two-tailed Student's t test).",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(G) Quantifications of the extent of fibrous cap and necrotic areas in brachiocephalic artery of Apoe-/- and Frs2SMCKO/Apoe-/- mice. (*p<0.05, **p<0.01 compared to Apoe-/-; unpaired two-tailed Student's t test).",
    "ncbi_link": "Apoe: 11816
Frs2: 327826"
  },
  {
    "caption": "(H) Measurement of Ki67+ cells (*p<0.05, ***p<0.001 compared to Apoe-/-; unpaired two-tailed Student's t test).",
    "ncbi_link": "Apoe: 11816"
  },
  {
    "caption": "(C) The degradation of 3HA-Pgc1 was analyzed as in (A) in cells bearing the CDC48 temperature-sensitive allele cdc48-6. Cells were grown 2,5 hours at 37C prior addition of cycloheximide. Inactivation of Cdc48 mutant protein was confirmed by stabilization of the ERAD substrate Erg1 in the same cells.",
    "ncbi_link": "CDC48: 851431
cdc48: 851431
Cdc48: 851431"
  },
  {
    "caption": "(A) Localization of chromosomally expressed GFP-Pgc1 from the constitutive ADH1 promoter in wt and doa10Δ cells. Arrowheads indicate GFP-Pgc1 labeling at the ER, which is stained by Sec63-Cherry. LDs were visualized upon staining with the neutral lipid dye MDH. On the bottom, box plot with quantitation of GFP-Pgc1 fluorescence intensity at the nuclear envelope in wt and doa10Δ. GFP-Pgc1 measurements were performed as described in the Materials and Methods section. Scale bar: 5 µm.",
    "ncbi_link": "ADH1: 854068
doa10: 854781"
  },
  {
    "caption": "(C) Crude membranes from wt and doa10Δ cells expressing 3HA-Pgc1 were subjected to the indicated treatments and subsequently fractionated into membrane pellet (P) and supernatant (S).(D) Crude membranes from wt and doa10Δ cells expressing 3HA-GFP-Pgc1275-321 were analyzed as in (C).",
    "ncbi_link": "Pgc1: 855895
doa10: 854781"
  },
  {
    "caption": "(A) Localization of GFP-Pgc1 in are1Δ are2Δ lro1Δ dga1Δ cells in presence (no LDs) or absence of DOA10 (no LDs doa10Δ). The ER was visualized by expression of Sec63-Cherry. Scale bar: 5 µm.",
    "ncbi_link": "are1: 850415
are2: 855753
dga1: 854419
lro1: 855742
DOA10: 854781
doa10: 854781"
  },
  {
    "caption": "(B) GFP-Pgc1 was expressed under the ADH1 promoter; LD formation was stimulated by galactose-induced expression of DGA1 in are1Δare2Δlro1Δ. Fluorescence microscopy was used to follow GFP-Pgc1 localization over time. LDs were visualized upon staining with the neutral lipid dye MDH. Scale bar: 5 µm.",
    "ncbi_link": "ADH1: 854068
are1: 850415
are2: 855753
DGA1: 854419
lro1: 855742"
  },
  {
    "caption": "(C) Photo-conversion of tdEOS-Pgc1 expressed under the ADH1 promoter; LD formation was stimulated by galactose-induced expression of DGA1 in are1Δare2Δlro1Δdoa10Δ cells. The red square marks the photo-converted region. The time (in minutes) after photoconversion is indicated. Arrowheads point LDs containing photoconverted tdEOS-Pgc1. Scale bar 5µm.",
    "ncbi_link": "ADH1: 854068
are1: 850415
are2: 855753
DGA1: 854419
lro1: 855742
doa10: 854781"
  },
  {
    "caption": "(D) FRAP experiment of GFP-Pgc1 in wt and doa10Δcells. Representative examples are shown. The bleached areas are marked by red squares and include a LD adjacent to ER. The time (in seconds) after photobleaching is indicated. Each graph shows average fluorescence intensities for 10 cells normalized to pre-bleached plotted over time. Error bars indicate standard deviation.",
    "ncbi_link": "doa10: 854781"
  },
  {
    "caption": "(A) Localization of GFP-tagged Pgc1 derivatives in which the hydrophobic hairpin (aa275-321) was replaced by membrane anchor of Scs2 (Pgc1Scs2MA) or Bos1 (Pgc1Bos1MA). ER and LDs were visualized by expression of Sec63-Cherry and MDH staining, respectively. Scale bar: 5 µm.",
    "ncbi_link": "Bos1: 850767
Pgc1: 855895
Scs2: 856856"
  },
  {
    "caption": "(B) The degradation of 3HA-Pgc1 or the indicated chimeras in wt and doa10Δ cells was analyzed as in Fig. 1A. The blot is representative of at least three independent experiments.",
    "ncbi_link": "doa10: 854781"
  },
  {
    "caption": "(C) The degradation of 3HA-GFP-Pgc1275-321 in wt and doa10Δ cells was analyzed as in Fig. 1A. The graph shows the average of four independent experiments; error bars represent the standard deviation.",
    "ncbi_link": "doa10: 854781"
  },
  {
    "caption": "(D) Localization of 3HA-GFP-Pgc1275-321 in doa10Δ cells. The ER was visualized by expression of Sec63-Cherry. Scale bar: 5 µm.",
    "ncbi_link": "doa10: 854781"
  },
  {
    "caption": "(A) The degradation of 3HA-Pgc1-GPAT160-216, containing GPAT4 hydrophobic hairpin (aa160-216) replacing the one of Pgc1 was analyzed in cells with the indicated genotype as in Fig. 1A. The graph shows the average of three independent experiments; error bars represent the standard deviation.",
    "ncbi_link": "GPAT4: 37852"
  },
  {
    "caption": "(B) Localization of GFP-Pgc1-GPAT4160-216 in cells with the indicated genotype. Arrowheads indicate GFP-Pgc1-GPAT4160-216 labeling at the ER, marked with Sec63-Cherry. LDs were visualized upon staining with MDH. Scale bar: 5 µm.",
    "ncbi_link": "GPAT4: 37852"
  },
  {
    "caption": "(D) Localization of GFP-Pgc1-GPAT160-216 in are1Δ are2Δ lro1Δ dga1Δ doa10Δ mutant (no LDs doa10Δ). The ER was visualized by expression of Sec63-Cherry. Scale bar: 5 µm.",
    "ncbi_link": "are1: 850415
are2: 855753
dga1: 854419
lro1: 855742
doa10: 854781"
  },
  {
    "caption": "D Bar graphs showing the percentage of unique insertions in Nfib and Foxp1 in tumours, LM1, LM8, LM9, and other LM cell lines normalized to the total number of insertions in a given sample. Dots represent individual samples (Tumours n = 16, LM1/8/9 n = 9, Other LM n = 9), means ± s.d., two-tailed Mann-Whitney U-test, n.s. = not significant.",
    "ncbi_link": "Foxp1: 108655
Nfib: 18028"
  },
  {
    "caption": " E Bar graphs representing mean Nfib mRNA expression normalized to HR1 cells. n = 2 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test, FC= fold change. F Bar graphs representing mean Foxp1 mRNA expression normalized to HR1 cells. n = 2 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test, FC= fold change. ",
    "ncbi_link": "Foxp1: 108655
Nfib: 18028"
  },
  {
    "caption": "A The kinetics of LM1 (n = 10), LM9 (n = 4), LM1 Nfib KO (n = 4), and LM9 Nfib KO (n = 4) tumour growth upon orthotopic injection of 250 x 103 cells into NOD/SCID mice. Curves show means of tumour volume ± s.d., two-way ANOVA group analysis of the times to reach 250 mm3 (dashed line).",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " B Kaplan-Meier plot depicting metastatic onset after tumour removal in mice injected orthotopically with LM1 (n = 5), LM9 (n = 4), LM1 Nfib KO (n = 3), or LM9 Nfib KO (n = 4) cells, two-tailed log-rank test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " C Nfib knockout abrogates metastasis in the orthotopic LM1 model. Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases at 25 (LM1) and 40 (KO) days after primary tumour removal; n = 3 mice, means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " D Nfib knockout impairs experimental metastases formation in the LM models. Kaplan-Meier plot showing metastatic incidence of animals inoculated i.v. with LM1 (n = 4), LM9 (n = 4), LM1 Nfib KO (n = 3), or LM9 Nfib KO (n = 5) cells, two-tailed log-rank test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " E Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 16 days after i.v. injection of LM1 or LM1 Nfib KO cells, n = 3 mice, means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " A Kaplan-Meier plot depicting metastasis onset after tumour removal in mice injected orthotopically with HR1 gCtrl (n = 13) or HR1 g4Nfib (n = 14), two-tailed log-rank test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " B Nfib overexpression in HR1 parental cells enhances metastasis in the orthotopic model. Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases at day 20 (HR1 gCtrl) and day 2 (HR1 g4Nfib) after primary tumour removal. n = 4 mice, means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " C Nfib overexpression in the HR1 parental cells enhances experimental metastases. Kaplan-Meier showing metastatic incidence of animals inoculated i.v. with HR1 gCtrl (n = 11) or HR1 g4Nfib (n = 11) cells, two-tailed log-rank test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " D Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 16 days after i.v. injection of HR1 gCtrl or HR1 g4Nfib cells. n = 4, means ± s.d., two tailed Student's t-test. ",
    "ncbi_link": "Nfib: 18028"
  },
  {
    "caption": " E NFIB overexpression enhances experimental metastases formation in the SUM159PT model. Kaplan-Meier survival analysis of animals inoculated i.v. with SUM159PT gCTRL (n = 5) or SUM159PT gNFIB (n = 6) cells, two-tailed log-rank test. ",
    "ncbi_link": "NFIB: 4781"
  },
  {
    "caption": " F Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 20 days after i.v. injection of SUM159PT gCTRL or SUM159PT gNFIB (n = 5), means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "NFIB: 18028"
  },
  {
    "caption": " C ChIP was performed in all murine cell lines (Nfib high-expression and the respective Nfib low-expression or KO controls) against Nfib followed by qPCR with primers specific for Ero1l promoter region proximal to transcription starting site (Ero1l_492 and Ero1l_493). Meg3 was used as control. Graph shows qPCR results with % input method as indicated (Nfib high-expression vs. the respective Nfib low-expression or KO controls). n = 2 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test, n.s. = not significant.",
    "ncbi_link": "Ero1l: 50527
Meg3: 17263
Nfib: 18028"
  },
  {
    "caption": " D Kaplan-Meier survival analysis of NSG mice inoculated i.v. with SUM159PT gNFIB shCTRL (n = 9), SUM159PT gNFIB sh1 ERO1A (n = 7), or SUM159PT gNFIB sh2 ERO1A (n = 7) cells. Two-tailed log-rank test. ",
    "ncbi_link": "ERO1A: 30001
NFIB: 4781"
  },
  {
    "caption": " E Representative bioluminescence images (left panel) and bar plot quantification (right panel) of lung metastases 8 (SUM159PT gNFIB shCTRL) and 20 (SUM159PT gNFIB sh1 ERO1A or SUM159PT gNFIB sh2 ERO1A) days after i.v. injection of the respective cells. n = 4, means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "ERO1A: 30001
NFIB: 4781"
  },
  {
    "caption": " F Kaplan-Meier survival analysis of overall survival of mice injected i.v. with SUM159PT gNFIB shCTRL (n = 10), SUM159PT gNFIB sh1 ERO1A (n = 12), or SUM159PT gNFIB sh2 ERO1A (n = 13) cells, two-tailed log-rank test. ",
    "ncbi_link": "ERO1A: 30001
NFIB: 4781"
  },
  {
    "caption": " A Bar graph showing the ROS levels in the NFIB models. The fluorescence signal was normalized to the blank. n = 2 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test. ",
    "ncbi_link": "NFIB: 4781"
  },
  {
    "caption": " C Left panel: Bar graph representing mean VEGFA mRNA expression in SUM159PT gCTRL and SUM159PT gNFIB breast cancer cell lines upon downregulation of ERO1A with two independent shRNAs (sh1 and sh2). Right panel: Bar graph representing mean VEGFA mRNA expression in lung extracts from animals inoculated i.v. with SUM159PT gNFIB shCTRL, SUM159PT sh1 ERO1A, or SUM159PT sh2 ERO1A cells. In both graphs n = 3 biological replicates and n = 2 technical replicates, means ± s.d., two-tailed Student's t-test, FC= fold change. ",
    "ncbi_link": "ERO1A: 30001
NFIB: 4781
VEGFA: 7422
VEGFA: 22339"
  },
  {
    "caption": " D Left panel: Representative images of CD31-positive endothelial structures in lungs. Scale bar, 1 mm. Right panel: Bar graphs showing lung metastases quantified as percentage of metastatic area per lung area and quantification of CD31 staining in the metastatic area. Means ± s.d., n = 8 shCTRL, n = 5 per sh1 ERO1A, and n = 6 sh2 ERO1A, two-tailed Student's t-test.",
    "ncbi_link": "ERO1A: 30001"
  },
  {
    "caption": " E Left panel: Bar graph showing average of master segments counted after incubation of HUVEC cells with conditioned medium from LM1, HR1, 4T1 (Nfib high-expression and the respective Nfib low-expression or KO controls) and SUM159PT gNFIB shCTRL, SUM159PT gNFIB sh1 ERO1A, SUM159PT gNFIB sh2 ERO1A cells. Human VEGF121(0.4 ng/μl) was added to SUM159PT gNFIB sh1 and sh2 ERO1A cells, n = 2 technical replicates, means ± s.d., two-tailed Student's t-test. Right panel: Representative images showing tube formation four hours after addition of conditioned medium from HR1 gCtrl or g4Nfib.Scale bar 100 μm. ",
    "ncbi_link": "ERO1A: 30001
Nfib: 18028
NFIB: 4781"
  },
  {
    "caption": "
 C Higher NFIB expression in iC10 and basal breast cancer subtype compared with the other subtypes using intClust (Dawson et al, 2013) and PAM50 classifications in the METABRIC cohort (n = 1980 across the 10 Intclust, iC). Boxplot represents NFIB expression values comprised between the 1st and the 3rd quartiles with the central band representing median expression value, and whiskers indicating the farthest data points that are still within the distance of 1.5 times the interquartile range (IQR). 
",
    "ncbi_link": "NFIB: 4781"
  },
  {
    "caption": " D, E Distant metastasis-free survival (D, n = 232) and overall survival (E, n = 241) plots generated using the Kaplan-Meier Plotter based on the mean expression using the signal intensity of the NFIB (213029_at) combined with the ERO1A (218498_s_at) probes. The cut-off was automatically set to split patients into two groups (median), high and low. The plots were generated using the signal intensity of the different probes in Affymetrix microarray gene expression data from TNBC patients of The Cancer Genome Atlas. Number of patients (n) and P values (two tailed log-rank test) are presented in the panels. ",
    "ncbi_link": "ERO1A: 30001
NFIB: 4781"
  },
  {
    "caption": "Whole-mount fluorescence view of E14.5-15.5 hearts from Npr3-sCreER;R26-tdTomato and Npr3-CreER;R26-tdTomato mice. Immunostaining for tdTomato, ESR and CDH5 on heart sections. C.M., compact myocardium; T.M., trabecular myocardium. Arrowheads, tdTomato+ESR- endocardial cells.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "Isolation of tdTomato- or tdTomato+ cells from E14.5 Npr3-sCreER;R26-tdTomato and Npr3-CreER;R26-tdTomato mice by FACS.",
    "ncbi_link": "tdTomato: 
Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "qRT-PCR of Cre, ESR, Npr3 and Cdh5 from tdTomato+ cells. Data are mean ± s.e.m.; n = 5; *P < 0.05.",
    "ncbi_link": "Cdh5: 12562
Cre: 2777477
ESR: 13982
Npr3: 18162"
  },
  {
    "caption": "Whole-mount fluorescence images of E14.5 Npr3-CreER;R26-Confetti and Npr3-sCreER;R26-Confetti mouse hearts. No Tam is used as control for leakiness of Npr3-sCreER.",
    "ncbi_link": "Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "Immunostaining for CDH5 on heart sections shows a significantly increase of endothelial cell labeling in Npr3-sCreER;R26-Confetti heart compared with Npr3-CreER;R26-Confetti heart (Tam). *P < 0.05; Data are mean ± s.e.m.; n = 5. Scale bars, 500 µm in c; 100 µm in d. Each image is representative of 5 individual biological samples.",
    "ncbi_link": "Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "Whole mount fluorescent images of E14.5 or E15.5 Npr3-sCreER;R26-LZLT and Npr3-CreER;R26-LZLT mouse hearts. No tam is as control for detecting leakiness of sCreER or CreER. Representative Immunostaining images for tdTomato, ESR and CDH5 on heart sections.",
    "ncbi_link": "Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "Quantification of the percentage of endocardial cells expressing tdTomato in Npr3-sCreER;R26-LZLT (sCreER) or Npr3-CreER;R26-LZLT (CreER) hearts. Data are mean ± s.e.m.; n = 5; *P < 0.05. Scale bars, 500 µm. Each figure is a representative of 5 individual biological samples.",
    "ncbi_link": "Cre: 2777477
ER: 2099
R26: 14910
Npr3: 18162"
  },
  {
    "caption": "Immunostaining for VEGFR2 on Npr3-sCreER;Kdrflox/flox heart section from mice without tamoxifen treatment (No Tam).",
    "ncbi_link": "Cre: 2777477
ER: 2099
Kdr: 16542
Npr3: 18162"
  },
  {
    "caption": "Whole-mount fluorescence images of Col1a2-sCreER;R26-tdTomato or Col1a2-CreER;R26-tdTomato hearts. Inserts indicate bright-field images.",
    "ncbi_link": "tdTomato: 
Col1a2: 12843
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "Immunostaining for tdTomato and ESR on heart sections. Arrowheads indicate valve mesenchyme. Quantification of the percentage of PDGFRa+ cells expressing tdTomato in Col1a2-sCreER;R26-tdTomato (sCreER) or Col1a2-CreER;R26-tdTomato (CreER) hearts. n.s., non-significant; Data are mean ± s.e.m.; n = 6; n.s., non-significant. Quantification of the percentage of tdTomato+ cells expressing ESR. *P < 0.05; Data are mean ± s.e.m.; n = 6; *P < 0.05.",
    "ncbi_link": "tdTomato: 
Col1a2: 12843
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "Immunostaining for PDGFRa in heart sections shows a significant increase of fibroblast labeling in valves of Col1a2-sCreER;R26-Confetti heart compared with Col1a2-CreER;R26-Confetti heart (Tam). Quantification of the percentage of fibroblasts expressing fluorescent reporters in cardiac valves. Data are mean ± s.e.m.; n = 5; *P < 0.05. Scale bars, 500 µm in c-e; 100 µm in h. Each figure is a representative of 5-6 individual biological samples.",
    "ncbi_link": "Col1a2: 12843
Cre: 2777477
ER: 2099
R26: 14910"
  },
  {
    "caption": "(D-F) Box plots showing diastolic (D) and systolic (E) diameters and cardiac  contractility analyses (percent fractional shortening) (F) performed using SOHA   approach for controls (Hand-Gal4  and UAS-dmiR-1 sponge) and Hand>sponge  dmiR-1 contexts at ages  one and five weeks. n = 20 hearts. Central band corresponds to median. Whiskers correspond to Min to Max. Box corresponds to interquartile range from 25th to 75th percentile. Data information: Scale bar = 20 µm. p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Gal4: 855828
Hand: 34379
miR-1: 12798026
sponge: 43404"
  },
  {
    "caption": "(G,G') Representative spot views generated using Imaris from  in situ hybridization with miRCURY  LNA probe for dmiR-1  and used for quantification of dmiR-1  levels. Spot views of dmiR-1 in hearts  of one-week-old control (UAS-mblRNAi) (G) and DM1 flies  (Hand>mblRNAi) (G') are shown. Each spot represents a pool of dmiR-1 transcripts detected in the same area. The zoom region in G corresponds to area in which FISH  signal was quantified. Data information: Scale bar = 40 µm.",
    "ncbi_link": "Hand: 34379
mbl: 36945
miR-1: 12798026"
  },
  {
    "caption": "(H, I) Scatter plot graph showing the signal intensity quantified in cardioblasts  of one- and five-week-old flies  for controls (UAS-Bru3, UAS-mblRNAi) and DM1  contexts (Hand>Bru3, Hand>mblRNAi). n = 9 hearts. Bars corresponds to mean ± SD. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Bru3: 39527
Hand: 34379
mbl: 36945"
  },
  {
    "caption": "(C-F') dmiR-1 binding site in 3'UTR-Mp  region is required to negatively regulate Mp expression in vivo. Adult hearts  from transgenic GFP-sensor lines carrying 3'UTRMp region with (UAS-GFP  3'UTRMp) or without dmiR-1 seed site (UAS-GFP  ∆3'UTRMp). These lines were combined with the UAS-dmiR1 line to generate double transgenic lines and tested for GFP expression  in non-targeted context (crossed with w1118) (C,E) or in heart-targeted context (crossed with heart  specific driver Hand-Gal4) (D,F). When crossed with Hand-Gal4, GFP expression  in Hand>GFP  3'UTRMp; dmiR1 line (carrying dmiR-1 seed site) (D') is attenuated in cardiac tube and  pericardial cells compared to Hand>GFP  ∆3'UTRMp; dmiR-1 line (lacking dmiR-1 seed site) (F'). Scale bar = 40 µm.",
    "ncbi_link": "GFP: 
Gal4: 855828
Hand: 34379
miR-1: 12798026
miR1: 12798026
Mp: 38769"
  },
  {
    "caption": "(K,L) Graphs of Mp  signal quantification in cardioblasts  from adult flies aged  one and five weeks for controls (UAS-mblRNAi, UAS-Bru3) and DM1  contexts (Hand>mblRNAi, Hand>Bru3) using CTCF  method. For each genotype 9 hearts  were analyzed and fluorescence intensity was measured in two regions from segment A3 and two regions from segment A4. Bars correspond to mean ± SD. Data information: p-value<0.05 considered statistically significant; (*) p-value = 0.033; (**) p-value = 0.021; (***) p-value = 0.0002; (****) p-value<0.0001. Non-parametric test Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Bru3: 39527
Hand: 34379
mbl: 36945"
  },
  {
    "caption": "(E-G) Box plots showing cardiac  variables (diastolic (E) and systolic (F) diameters) and percent fractional shortening (G) for controls (Hand-Gal4  and UAS-Mp) and Mp  overexpression (Hand>Mp) conditions at one and five weeks. Notice an increase in diastolic  and systolic  diameters  with reduced cardiac  contractility in Hand>Mp  in comparison to controls. n = 20 hearts. Central band corresponds to median. Whiskers correspond to Min to Max. Box corresponds to interquartile range from 25th to 75th percentile. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Gal4: 855828
Hand: 34379
Mp: 38769"
  },
  {
    "caption": "(A-B') Adult heart  of 1 week of age labeled for Mp  (green) and actin  (red) for control (UAS-Mp  RNAi) (A,A') and mutant (Hand>Mp  RNAi) contexts (B,B'). Data information: Scale bar = 20µm.",
    "ncbi_link": "Hand: 34379
Mp: 38769"
  },
  {
    "caption": "(C) Fluorescence signal intensity quantification for Mp expression  in cardioblasts  in adult heart  of 1 week for control (UAS-Mp  RNAi) and mutant (Hand>Mp  RNAi) contexts using CTCF  method. For each genotype 9 hearts  were analyzed and fluorescence intensity was measured in two regions from segment A3 and two regions from segment A4. Bars correspond to mean ± SD. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Hand: 34379
Mp: 38769"
  },
  {
    "caption": "(D-F) Box plots showing cardiac  size analyzes (diastolic  (D) and  systolic  diameters (E)) and percent fractional shortening (F) performed by SOHA   approach for controls (Hand-Gal4  and UAS-Mp  RNAi) and mutant (Hand>Mp  RNAi) contexts at 1 and 5 weeks of age, showing reduced size of cardiac tube in Hand>Mp  RNAi context in comparison to the Hand-Gal4  control. n = 20 hearts. Central band corresponds to median. Whiskers correspond to Min to Max. Box corresponds to interquartile range from 25th to 75th percentile. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (**) p-value =0.021, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest.",
    "ncbi_link": "Gal4: 855828
Hand: 34379
Mp: 38769"
  },
  {
    "caption": "(A, B) (A) Col15A1   transcript levels tested by  RT-qPCR and (B) Col15A1  protein levels tested by Western blot in cardiac  samples from healthy donors and from DM1 patients  with (DCM+) and without DCM   (DCM-). Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Parametric t-test was performed to compare control samples and samples of interest in A, B",
    "ncbi_link": "Col15A1: 1306"
  },
  {
    "caption": "(C) miR-1 levels tested by RT-qPCR in cardiac  samples from healthy donors and from DM1 patients. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Parametric t-test was performed to compare control samples and samples of interest in C.",
    "ncbi_link": "miR-1: 406904"
  },
  {
    "caption": "(D, F) Box plots showing cardiac  variables (diastolic (D) and systolic (E) diameters and percent fractional shortening (F)) assessed by SOHA  approach for controls (UAS-Bru3; Mp  RNAi and UAS-UPRT; Bru3), Mp  rescue (Hand>Bru3; Mp  RANi) and DM1  context (Hand>UPRT; Bru3) at five weeks of age  showing rescue of diastolic   and systolic  diameters in Hand>Bru3; Mp  RNAi in comparison to controls (D,E) and rescue of cardiac  contractility (F) n = 20 hearts. Central band corresponds to median. Whiskers correspond to Min to Max. Box corresponds to interquartile range from 25th to 75th percentile. Data information: p-value<0.05 considered statistically significant. (*) p-value = 0.033, (***) p-value =0.0002. (****) p-value<0.0001. Non-parametric Mann Whitney test was performed to compare control samples and samples of interest in D,E,F.",
    "ncbi_link": "UPRT: 
Bru3: 39527
Hand: 34379
Mp: 38769"
  },
  {
    "caption": "B, C Both  mRNA and protein levels of RBM47 were elevated in SeV-infected (B) or IFN-α-stimulated (C) 293T,  HFF, HUVEC, and THP-1  cells. Cells were infected with SeV (MOI = 1) or stimulated with IFN-α for 6 or 12 h, and the expression of RBM47 mRNA  (at 6 and 12 h post treatment) and protein (at 6 and 12 h post treatment) were tested. The PCR  results are represented as the means ± SD of n = 3 biological replicates. Data information: Data are representative of n = 3 independent experiments. NS, non-significant; * P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "RBM47: 54502"
  },
  {
    "caption": "C, D Levels of  viral genome, protein, and  progeny of VSV (C) or HSV-1 (D) were quantified in virus-infected  293T cells with or without RBM47 ectopic expression at the indicated time points. The viral protein levels were tested 12 h post VSV infection and 24 h post HSV-1  infection.The PCR  and viral titer data are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments.**P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "RBM47: 54502"
  },
  {
    "caption": "D, E mRNA expression of IFIT1, ISG15, and Cig5 in  SeV-infected  293T  cells overexpressing  RBM47 (D) or RBM47  knocked down cells (E). Cells were infected with SeV for 24 h, and  gene expression was determined using qRT-PCR.The PCR results are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; * P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "IFIT1: 3434
ISG15: 9636
RBM47: 54502
Cig5: 91543"
  },
  {
    "caption": "F The expression of  IFIT1, ISG15, and  Cig5 in RBM47-overexpressing or control  293T  cells stimulated by  IFN-α for 12 h. The PCR results are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; * P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "IFIT1: 3434
ISG15: 9636
RBM47: 54502
Cig5: 91543"
  },
  {
    "caption": "G The  expression of  IFIT1, ISG15, and Cig5 in WT and RBM47+/- peritoneal  macrophages stimulated by  IFN-α for 12 h. The PCR results are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; * P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). ",
    "ncbi_link": "IFIT1: 15957
ISG15: 100038882
RBM47: 245945
Cig5: 58185"
  },
  {
    "caption": "B IFNAR1 mRNA stability after DRB treatment. 293T cells were transfected with  RBM47-Flag or empty vectors and treated with DRB (50 μg/mL). Total RNA was harvested at 0, 15, 30, 45, and 60 min, and IFNAR1 mRNA levels were measured using qRT-PCR and normalized to  β-actin. The PCR results are represented as the means ± SD of n = 3 biological replicates. Data information: Data are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test).",
    "ncbi_link": "Flag: 
β-actin: 60
IFNAR1: 3454
RBM47: 54502"
  },
  {
    "caption": "A mRNA of  IFNAR1, but not IFNAR2  or STAT1, was stabilized by  RBM47 ectopic expression in 293T cells with or without IFN-α  stimulation. Cells were treated with IFN-α or  PBS for 6 h, and the relative gene expression levels were determined using qRT-PCR.The PCR  results are represented as the means ± SD of n = 3 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). The data shown are representative of three independent experiments.",
    "ncbi_link": "IFNAR1: 3454
IFNAR2: 3455
RBM47: 54502
STAT1: 6772"
  },
  {
    "caption": "F, G  Protein levels of IFNAR1 and phosphorylation levels of TYK2, STAT1, and STAT2 in RBM47-overexpressing (F) or knockdown (G) 293T  cells. Cells were treated with PBS or IFN-α for 6 h, and the relative band densities were analyzed using ImageJ software and normalized to GAPDH. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). The data shown are representative of three independent experiments.",
    "ncbi_link": "RBM47: 54502"
  },
  {
    "caption": "G RBM47+/+ and RBM47+/- mice were infected with HSV-1 (1× 107 pfu) via caudal vein injection. Viral genome DNA and progeny titers were tested using blood samples from infected mice. Data are represented as the means ± SD of n = 6 biological replicates. H qRT-PCR analysis of IFNAR1 and Cig5 mRNA in blood samples from HSV-1-infected  mice. The PCR results are represented as the means ± SD of n = 6 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; * P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). ",
    "ncbi_link": "IFNAR1: 15975
RBM47: 245945
Cig5: 58185"
  },
  {
    "caption": "D The mRNA levels of VSV and RBM47  in blood  samples of  IFNAR1 deficient (IFNAR1-/-) mice (n = 6 per group) infected with VSV. Mice were infected with shmRBM47 or control lentivirus for 7 days and then challenged with VSV  for another 24 h. Each dot represents one  mouse. The  PCR results are represented as the means ± SD of n = 6 biological replicates. Data information: The data shown are representative of n = 3 independent experiments. NS, non-significant; **P ≤ 0.01, and ***P ≤ 0.001 (Student's t-test). ",
    "ncbi_link": "IFNAR1: 15975
RBM47: 245945"
  },
  {
    "caption": "Plot showing the average Z-scores of 210 endolysosomal genes plotted against the negative log10 of the P values from the one-sample t-test of whether average Z-score ≠ 0. Green circles represent significantly upregulated genes (Z > 0 and P < 0.05). Magenta circles represent significantly downregulated genes (Z < 0 and P < 0.05). Grey circles represent genes whose expression is not significantly changed (P > 0.05). All comparisons were between cancers and normal cells from the same tissue. Dashed line shows position on Y-axis that corresponds to P = 0.05. Positions of MCOLN1 (red circle), VAC14 (blue circle), and MTM1 (yellow circle) are indicated. Inset, schematic showing that Mtm1 and Vac14 regulate the levels of PI(3,5)P2, and thereby, influence TRPML1 activity.",
    "ncbi_link": "MCOLN1: 57192
MTM1: 4534
VAC14: 55697"
  },
  {
    "caption": "Bar graph showing the relative expression of the indicated genes in the indicated cell types. Values were normalized to respective 'HN31+HRAS shRNA' average and represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "Western blots performed on extracts isolated from the indicated cells probed with antibodies against Tfeb and tubulin. Molecular weights are shown on the left. Bar graph shows relative Tfeb levels in the indicated samples. Values were normalized to 'HN31+HRAS shRNA' and represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "Bar graph showing the relative expression of the indicated genes in the indicated cell types. Values were normalized to respective 'HN31+HRAS shRNA' average and represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "Bar graph showing the relative expression of MCOLN1 in the indicated cell types. Values were normalized to HT1197 average and represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "Representative images showing Ki67-labeling in xenografts generated from implantation of HN31 cells stably expressing control shRNA (left) or MCOLN1 shRNA (right). Pseudocolored panels show the representative distribution Ki67 positive or negative nuclei. Scale bars shown (0.5 mm) apply to all panels.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "Bar graphs showing the relative cell numbers in UMSCC-22A-HRASWT cells following the indicated perturbations. All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "Kaplan-Meier curves showing the survival of patients stratified on the basis of MCOLN1 expression in BLCA and HNSC patients whose tumors were wild-type for HRAS (right) or carried oncogenic HRAS mutations (left). Statistical test employed was the Mantel-Cox log-rank test.",
    "ncbi_link": "HRAS: 3265
MCOLN1: 57192"
  },
  {
    "caption": "Representative Western blots generated using extracts from cells of expressing oncogenic HRAS and controls treated with ML-SI1 as indicated. The primary antibodies used are indicated on the right. Bar graph showing quantification of the Western blots shown in (A). All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "HRAS: 3265"
  },
  {
    "caption": "Bar graph showing relative levels of trpml mRNA in Drosophila larval brain extracts from control animals and animals expressing dRasG12V in glia. All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "dRas: 41140
trpml: 40152"
  },
  {
    "caption": "Representative images of Drosophila 3rd instar larvae expressing the indicated transgenes in glial cells. repo-GAL4 was used to drive the expression of UAS-dRasG12V in glia. Images shown are volumetric reconstructions of confocal stacks. The various anatomical structures of the larval brain are annotated. VNC refers to the 'ventral nerve chord', which is distinct from dorsal hemispheres of the brain. GFP staining represents the total glial membranes in the larval brains. Scale bar, 100μm.",
    "ncbi_link": "GAL4: 855828
dRas: 41140
repo: 47285"
  },
  {
    "caption": "Representative Western blots generated using macrophage extracts isolated from 3rd instar larvae of the indicated genotypes. He-GAL4 was used to drive the expression of UAS-dRasG12V in macrophages. The primary antibodies used are indicated on the right. Bar graph showing quantification of the Western blots shown in (D). All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "GAL4: 855828
He: 117464
dRas: 41140"
  },
  {
    "caption": "Representative Western blots generated using fat-body extracts isolated from 3rd instar larvae of the indicated genotypes. cg-GAL4 was used to drive the expression of UAS-HRASG12V in larval fat-bodies. The primary antibodies used are indicated on the right. Bar graph showing quantification of the Western blots shown in (F). All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "cg: 36571
GAL4: 855828
HRAS: 3265"
  },
  {
    "caption": "Representative Western blots generated using extracts from HN31 cells stably expressing the MCOLN1 shRNA. Samples treated with exogenous cholesterol for 3 hours are indicated at the bottom. Primary antibodies used are indicated on the right.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "Representative Western blots generated using extracts from HN31 cells stably expressing the MCOLN1 shRNA. Samples treated with exogenous cholesterol for 3 hours are indicated at the bottom. Bar graph showing quantification of the Western blots in (F). All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was ANOVA.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "Confocal images of control and MCOLN1 shRNA-expressing HN31 cells treated with the cholesterol sensor, filipin. Scale bar (10μm) shown in the panel on the top applies to both panels. Bar graph showing the quantification of the internalized filipin staining in HN31 cells after MCOLN1 knockdown. All values represent mean±SEM. Data points represent values from biological replicates. Statistical test employed was Student's t-test.",
    "ncbi_link": "MCOLN1: 57192"
  },
  {
    "caption": "a-e, Scanning electron microscopy (SEM) images of fly eyes expressing DTS7 with or without the indicated HDAC6 transgenes. Lower panels, magnification of ommatidia. a, Normal eyes in DTS7 flies reared at 22 °C. b, Rough eyes in DTS7 flies reared at 28 °C. c, d, Degeneration was suppressed by expression of Drosophila HDAC6 (dHDAC6; c) or human HDAC6 (hHDAC6; d), but not a catalytically dead mutant of hHDAC6 (cat. mut.; e).",
    "ncbi_link": "HDAC6: 32461
HDAC6: 10013///32461
DTS7: 39628"
  },
  {
    "caption": "f-j, SEM images of fly eyes expressing AR52 with or without the indicated HDAC6 transgenes. Lower panels, magnification of ommatidia. f, Normal eyes in AR52 flies reared without (-) DHT. g, Rough eyes in AR52 flies reared with (+) DHT. Degeneration was suppressed by expression of Drosophila HDAC6 (h) or human HDAC6 (i), but not a catalytically dead mutant of human HDAC6 (j).",
    "ncbi_link": "AR52: 367
HDAC6: 10013///32461"
  },
  {
    "caption": "k-p, Detection of UPS reporter in imaginal eye discs from third-instar larvae by confocal microscopy. High level fluorescence was found in flies expressing GFP (k, positive control), but fluorescence was barely detectable in control flies expressing CL1-GFP (l, negative control). CL1-GFP accumulates in DTS7flies with temperature-dependent proteasome impairment (compare m to n) and in AR52flies with ligand-dependent degeneration (compare o to p). The retinal phenotypes of 200 to >1,000 flies of each genotype were examined. Quantitative analyses of eye phenotypes and proteasome impairment are presented in Supplementary Figs S2 and S3, respectively. (DHT, dihydrotestosterone.)",
    "ncbi_link": "CL1: 
AR52: 367
DTS7: 39628"
  },
  {
    "caption": "a-e, Representative examples of autophagic vacuoles detected by TEM in retinal sections used to generate the quantitative data shown in (f). a, An autophagosome (red arrow) containing cytoplasmic contents in a photoreceptor neuron from an AR52fly reared on DHT. b, Higher magnification of the autophagosome in a. c, Multiple autophagolysosomes (red arrows) containing dense, amorphous material from an AR52fly reared on DHT. d, A juxtanuclear multilamellar body (red arrow) from a DTS7fly reared at 28 °C. e, A multivesicular body (red arrow) from a DTS7fly reared at 28 °C. f, A significant increase in the frequency of neurons with autophagic figures in DTS7 flies reared at 28 °C compared to those reared at 22 °C, and in AR52 flies reared on DHT compared to those reared off DHT. Data show mean ± s.d., n = 59-82 neurons in 5 sections per condition. No accumulation of autophagic figures was found in AR12 flies.",
    "ncbi_link": "AR12: 367
AR52: 367
DTS7: 39628"
  },
  {
    "caption": "g-l, SEM images of fly eyes expressing the indicated transgenes. RNAi knockdown (KD) of atg6 and atg12 enhances degeneration in DTS7 flies reared at 28 °C (compare h, i to g) and AR52 flies reared on DHT (compare k, l to j). 200 to >1,000 fly eyes of each genotype were examined. Quantitative analyses of eye phenotypes are presented in Supplementary Fig. S2. (N, nucleus; Rh, rhabdomere.)",
    "ncbi_link": "AR52: 367
atg12: 39383
atg6: 42850
DTS7: 39628"
  },
  {
    "caption": "a, b, d, Western blots from flies expressing the indicated transgenes. a, Steady state levels of AR52 protein are reduced in flies overexpressing Drosophila HDAC6, but are elevated in flies in which atg6 or atg12 has been knocked down. b, Western blots showing the temporal profile of AR52 protein monomer and high molecular weight aggregate levels after a brief pulse of expression. AR52 protein became detectable by 2.5 h after treatment with RU486, reached a peak at 10 h, and then slowly decayed. c, A logarithmic plot of AR52/actin ratios was used to determine the line of best fit by regression analysis (y = Ae-Kx). R2 = 0.9117 (AR52 - DHT), R2 = 0.7808 (AR52 + DHT), R2 = 0.9719 (HDAC6 + (AR52 - DHT)), R2 = 0.9644 (HDAC6 + (AR52 + DHT)). Half-life was determined by the slope of the best fit line with the equation t1/2 = 0.693/K. Half-life of AR52 in vivo was reduced ∼2-fold in flies co-expressing Drosophila HDAC6 and did not differ significantly in the presence (broken lines) or absence (solid lines) of DHT. Plots of the mean AR52/actin ratios are shown in Supplementary Fig. S12. d, Flies co-expressing Drosophila HDAC6 showed a nearly identical profile of induced expression as in b, but AR protein decayed at an accelerated rate. Exogenous Drosophila HDAC6 was detected by immunoblot against the V5 epitope.",
    "ncbi_link": "AR52: 367
atg12: 39383
atg6: 42850
HDAC6: 10013///32461"
  },
  {
    "caption": "a-l, SEM images of fly eyes expressing the indicated transgenes. The rough eye phenotypes caused by proteasome mutation (a) or by expression of polyQ-expanded AR (b) were both suppressed by rearing flies on the TOR inhibitor rapamycin (c, d). e, f, Rapamycin failed to suppress degeneration in an autophagy-deficient background created by knockdown of atg12, confirming that rescue by rapamycin is autophagy-dependent. g, h, Rapamycin also failed to suppress degeneration when HDAC6 levels were knocked down, demonstrating that suppression via the TOR pathway is HDAC6-dependent. k, j, HDAC6 failed to suppress degeneration in an autophagy-deficient background, confirming that rescue by HDAC6 is dependent on autophagy (compare k, l to i, j). 200 to >1,000 fly eyes of each genotype were examined. Quantitative analyses of eye phenotypes are presented in Supplementary Fig. S2.",
    "ncbi_link": "AR: 367
atg12: 39383
HDAC6: 10013///32461"
  },
  {
    "caption": "3‐month‐old wild‐type (C57BL/6), Ltbr−/−, Lta−/−, LIGHT−/−, and Ltbr−/−Hox11−/− mice; percentage of mice with at least one ANA.",
    "ncbi_link": "Lta: 16992
Ltbr: 17000
Hox11: 21908
LIGHT: 50930"
  },
  {
    "caption": "6‐month‐old Ltbr−/− mice (n = 15); titers of individual mice.",
    "ncbi_link": "Ltbr: 17000"
  },
  {
    "caption": "LIA of 6‐month‐old Ltbr−/− mice, wild‐type mice, and 3‐month‐old Rorγt‐Ltb−/− mice.",
    "ncbi_link": "Ltb: 16994
Ltbr: 17000
Rorγt: 19885"
  },
  {
    "caption": "Bone marrow cells from wild‐type or Ltbr−/− mice were transferred at neonatal age into lethally irradiated wild‐type or Ltbr−/− mice; percentage of mice with at least one ANA. ANA were determined with LIA at the age of 3 months.",
    "ncbi_link": "Ltbr: 17000"
  },
  {
    "caption": "Total IgG from nude mice engrafted with Ltbr−/− or wild‐type thymi was determined by ELISA. No significant differences were found. Data represent means ± s.e.m.",
    "ncbi_link": "Ltbr: 17000"
  },
  {
    "caption": "Ltbr−/− mice were treated or not with antibiotics from birth (upper panel), conventionalized or germfree wild‐type mice were treated with the LTβR‐Fc fusion protein from gestational day 18 until 6 weeks after birth (lower panel); percentage of mice with at least one ANA. ANA were tested with LIA at the age of 3 months.",
    "ncbi_link": "Ltbr: 17000"
  },
  {
    "caption": "Real‐time PCR for SFB in luminal, mucosal, and fecal samples of multiple ANA‐positive and ANA‐negative Ltbr−/− mice. Analysis with ANOVA, P = 0.02 for differences between groups, n = 4 mice per group. Data represent means ± s.e.m.",
    "ncbi_link": "Ltbr: 17000"
  },
  {
    "caption": "LTβR‐Fc‐treated wild‐type or IL17R−/− mice; percentage of mice with at least one ANA. E denotes gestational day. ANA were determined with LIA at the age of 3 months",
    "ncbi_link": "IL17R: "
  },
  {
    "caption": "A. Mitochondrial non-heme iron in ABCB8 NTG and TG mice. N=4 mice for NTG and 6 mice for TG. * P=0.021 with two-tailed unpaired T-test.B. Cytosolic non-heme iron in ABCB8 NTG and TG mice. N=4 mice for NTG and 6 mice for TG. Two-tailed unpaired T-test was performed.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "C. Baseline ejection fraction of littermate ABCB8 NTG and TG mice. N=6 mice in each group. Two-tailed unpaired T-test was performed.D. Baseline fractional shortening of littermate ABCB8 NTG and TG mice. N=6 mice in each group. Two-tailed unpaired T-test was performed.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "A. Cardiac function in ABCB8 NTG and TG mice undergoing sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed for each time point. * P<0.05 compared with TG-sham at the same time point. $ P<0.05 compared with NTG-I/R at the same time point. § P<0.05 compared with NTG-sham at the same time point. N=5 mice for NTG-sham and NTG-I/R, and N=6 mice for TG-sham and TG-I/R. Exact P-values are included in Appendix Table S3.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "C. Quantification of apoptosis in ABCB8 TG and NTG mice with indicated procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.035. N=4 mice for TG-I/R, and N=6 mice for all other groups.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "D. Nppa expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=3.24E-4 NTG-sham vs. NTG-I/R. * P=0.002 TG-sham vs. TG-I/R. * P=8E-6 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and NTG-I/R, and N=6 mice for TG-sham and TG-I/R.E. Nppb expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P<1E-8 NTG-sham vs. NTG-I/R. * P=0.032 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and NTG-I/R, and N=6 mice for TG-sham and TG-I/R.F. Myh7 expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.04 NTG-sham vs. NTG-I/R. * P=0.034 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and NTG-I/R, and N=6 mice for TG-sham and TG-I/R. All data are expressed as mean ± SEM. N.S. = not signigicant.",
    "ncbi_link": "Myh7: 140781
Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "A. Representative H&E staining of peri-infarct area demonstrated reduced cellular injury in ABCB8 TG mice after I/R. Scale bar = 115μm.B. Representative H&E and Masson Trichrome (MT) staining in mouseheart 28 days after indicated procedure. Scale bar = 1100μm.C. Quantification of tissue fibrosis in ABCB8 NTG and TG mice subjected to I/R. * P=0.047 with two-tailed unpaired T-test. 2-3 sections from each mice were quantified; N=4 mice for NTG and N=6 mice for TG.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "D. Nppa expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.006 NTG-sham vs. NTG-I/R. * P=0.015 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and TG-I/R, N=6 mice for TG-sham, and N=4 mice for NTG-I/R.E. Nppb expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.001 NTG-sham vs. NTG-I/R. * P=0.004 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and TG-I/R, N=6 mice for TG-sham, and N=4 mice for NTG-I/R.F. Myh7 expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.002 NTG-sham vs. NTG-I/R. * P=0.011 NTG-I/R vs. TG-I/R. N=5 mice for NTG-sham and TG-I/R, N=6 mice for TG-sham, and N=4 mice for NTG-I/R. All data are expressed as mean ± SEM. N.S. = not signigicant.",
    "ncbi_link": "Myh7: 140781
Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "G. Nppa expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.002 PBS-sham vs. PBS-I/R. * P=0.02 DFO-sham vs. DFO I/R. * P=0.007 PBS-I/R vs. BPD I/R. N=6 mice for PBS-sham and DFO-sham, N=4 mice for all other groups.H. Nppb expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P= 0.0007 PBS-sham vs. PBS-I/R. * P= 0.014 DFO-sham vs. DFO I/R. * P= 0.003 PBS-I/R vs. BPD I/R. N=6 mice for PBS-sham and DFO-sham, N=4 mice for all other groups.I. Myh7 expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.0001 PBS-sham vs. PBS-I/R. * P=0.038 DFO-sham vs. DFO I/R. * P=0.006 PBS-I/R vs. BPD I/R. N=6 mice for PBS-sham and DFO-sham, N=4 mice for all other groups. All data are expressed as mean ± SEM. N.S. = not signigicant.",
    "ncbi_link": "Myh7: 140781
Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "A. Cardiac mitochondrial iron in ABCB8 KO and WT mice with indicated treatment harvested 4 weeks after the tamoxifen treatment. ANOVA followed by post-hoc Tukey test was performed. * P=0.02 WT-vehicle vs. WT-BPD. * P= 0.001 WT-vehicle vs. ABCB8 KO-vehicle. * P=0.004 ABCB8 KO-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "B. Ejection fraction in ABCB8 KO and WT mice with indicated treatment 4 weeks after gene knockout. ANOVA followed by post-hoc Tukey test was performed. * P<1E-8 WT-vehicle vs. ABCB8 KO-vehicle. * P<1E-8 ABCB8-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "C. Fractional shortening in ABCB8 KO and WT mice with indicated treatment 4 weeks after gene knockout. ANOVA followed by post-hoc Tukey test was performed. * P<1E-8 WT-vehicle vs. ABCB8 KO-vehicle. * P<1E-8 ABCB8-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "D. Nppa expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.017 WT-vehicle vs. ABCB8 KO-vehicle. * P=0.01 ABCB8-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups.E. Nppb expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.001 WT-vehicle vs. ABCB8 KO-vehicle. * P=0.0003 ABCB8-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups.F. Myh7 expression in mice subjected to sham or I/R procedure. ANOVA followed by post-hoc Tukey test was performed. * P=0.011 WT-vehicle vs. ABCB8 KO-vehicle. * P=0.045 ABCB8-vehicle vs. ABCB8 KO-BPD. N=8 for WT-vehicle and N=7 for all other groups. All data are expressed as mean ± SEM. N.S. = not signigicant.",
    "ncbi_link": "ABCB8: 74610
Myh7: 140781
Nppa: 230899
Nppb: 18158"
  },
  {
    "caption": "A. Representative western blot demonstrating ABCB8 overexpression in H9c2 cells. EV = empty vector. N=3 independent samples for each group.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "B. Complex I ROS production in mitochondria with ABCB8 downregulation with or without rotenone. ANOVA followed by post-hoc Tukey test was performed. N= 6 independent samples for each group.",
    "ncbi_link": "ABCB8: 362302"
  },
  {
    "caption": "C. Complex III ROS production in mitochondria with ABCB8 downregulation with or without antimycin A. ANOVA followed by post-hoc Tukey test was performed. N= 6 independent samples for each group.",
    "ncbi_link": "ABCB8: 362302"
  },
  {
    "caption": "D. Complex I ROS production in mitochondria with ABCB8 overexpression with or without rotenone. EV= empty vector. ANOVA followed by post-hoc Tukey test was performed. N=9 independent samples for EV-baseline and N=8 independent samples for the other groups.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "E. Complex IIIROS production in mitochondria with ABCB8 overexpression with or without antimycin A. EV= empty vector. ANOVA followed by post-hoc Tukey test was performed. N=9 independent samples for EV-baseline and N=8 independent samples for the other groups.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "H. The levels of lipid peroxidation products in ABCB8 KO mice with or without chelator treatment. N=4 mice for WT-vehicle, N=6 mice for ABCB8 KO-vehicle, and N=5 mice for all other groups. ANOVA followed by post-hoc Tukey test was performed. * P=0.004 WT-vehicle vs. ABCB8 KO-vehicle. * P=1E-6 ABCB8 KO-vehicle vs. ABCB8 KO-BPD.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "I. Lipid peroxidation products in ABCB8 TG and NTG mice two days after I/R. N=6 mice for NTG-sham, and N=4 mice for the other groups. ANOVA followed by post-hoc Tukey test was performed. * P=0.024 NTG-sham vs. NTG-I/R. * P=0.016 NTG-I/R vs. TG-I/R. All data are expressed as mean ± SEM. N.S. = not signigicant.",
    "ncbi_link": "ABCB8: 74610"
  },
  {
    "caption": "A. Mitochondrial aconitase activity in H9c2 cells with or without ABCB8 overexpression and treated with or without H2O2. N=4 independent samples for each group. ANOVA followed by post-hoc Tukey test was performed. * P=0.0004 EV-PBS vs. EV-H2O2. * P=0.0001 EV-H2O2 vs. ABCB8-H2O2.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "B. Complex I activity in H9c2 cells with or without ABCB8 overexpression and treated with or without H2O2. N=6 independent samples for each group. ANOVA followed by post-hoc Tukey test was performed. * P=0.0005 EV-PBS vs. EV-H2O2. * P=0.00001 EV-H2O2 vs. ABCB8-H2O2.C. Complex II activity in H9c2 cells with or without ABCB8 overexpression and treated with or without H2O2. N=6 independent samples for each group. ANOVA followed by post-hoc Tukey test was performed. * P=0.001 EV-PBS vs. EV-H2O2. * P=0.001 EV-H2O2 vs. ABCB8-H2O2.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "D. Complex IV activity in H9c2 cells with or without ABCB8 overexpression and treated with or without H2O2. N=6 independent samples for each group. ANOVA followed by post-hoc Tukey test was performed. * P=0.0008 EV-PBS vs. EV-H2O2. * P=0.0006 EV-H2O2 vs. ABCB8-H2O2.",
    "ncbi_link": "ABCB8: 11194"
  },
  {
    "caption": "Representative images of K5creTg/+ CARD14E138A+/+ and K5creTg/+ CARD14E138ATg/+ pups at E18.5.",
    "ncbi_link": "CARD14: 79092
cre: 2777477
K5: 110308"
  },
  {
    "caption": "Representative image of 6 month-old Malt1fl/fl K5cretg/+ CARD14E138A+/+ and Malt1fl/fl K5cretg/+ CARD14E138Atg/+ mice.",
    "ncbi_link": "CARD14: 79092
cre: 2777477
K5: 110308
Malt1: 240354"
  },
  {
    "caption": "Body weight and ear thickness of untreated WT and Malt1fl/fl K5creTg/+ CARD14E138ATg/+ male and female mice (between 4 and 7 months old). Each symbol represents one mouse; the line represents the mean value (n≥4 mice per group). WT = Malt1fl/fl K5cre+/+ CARD14E138A+/+, Malt1fl/fl K5cre+/+ CARD14E138ATg/+ and Malt1fl/fl K5creTg/+ CARD14E138A+/+ mice. Statistical difference between two groups was determined using a Mann-Whitney U-test (ns: p-value>0.05)",
    "ncbi_link": "CARD14: 79092
cre: 2777477
K5: 110308
Malt1: 240354"
  },
  {
    "caption": "Representative H&E-stained histological sections of ear and skin tissue of Malt1fl/fl K5cre+/+ CARD14E138A+/+ and Malt1fl/fl K5creTg/+ CARD14E138ATg/+ mice (scale bar represents 100 μm).",
    "ncbi_link": "CARD14: 79092
cre: 2777477
K5: 110308
Malt1: 240354"
  },
  {
    "caption": "Changes in relative body weight and ear thickness upon CARD14E138A induction with tamoxifen. Malt1EKO = Malt1fl/fl. The combined results of five independent experiments are shown (Malt1+/+ WT n=17, Malt1fl/fl WT n=8, Malt1+/+ ieCARD14E138A n=18, Malt1fl/fl ieCARD14E138A n=12).",
    "ncbi_link": "CARD14: 79092
Malt1: 240354"
  },
  {
    "caption": "mRNA expression levels of the indicated genes in ears relative to reference genes (Hprt1, Rpl13a and Tbp1). Each symbol represents one mouse; the line represents the mean value (n≥3).",
    "ncbi_link": "Hprt1: 
Rpl13a: 
Tbp1: "
  },
  {
    "caption": "Changes in relative ear thickness and body weight in vehicle- and MALT1 inhibitor-treated mice upon CARD14E138A induction. M1 inh= MALT1 inhibitor, WT = K14creERTg/+ Rosa26+/+, ieCARD14E138A = K14creERTg/+ Rosa26LSL-CARD14-E138A/+. Combined results of two independent experiments are shown (WT + vehicle: n=9, WT + M1 inh: n=8, ieCARD14E138A + vehicle: n=9, ieCARD14E138A + M1 inh: n=10).",
    "ncbi_link": "Rosa26: 
CARD14: 79092
cre: 2777477
ER: 2099
K14: 16664"
  },
  {
    "caption": "B (Top) Semiquantitative  RT-PCR of UPF1SL or UPF1LL transcript levels following transfection of HEK-293 cells with a NT siRNA or a siRNA that specifically targets the UPF1LL isoform. (Bottom) Venn diagram (to scale) of overlapping targets identified from RNA-seq following total UPF1 or UPF1LL-specific knockdown. Depicted are genes that increased in abundance at least 1.4-fold (FDR < 0.05) and met read count cutoffs in both datasets. P value indicates enrichment of genes that increased in abundance at least 1.4-fold (FDR < 0.05) with  UPF1LL-specific knockdown among those regulated by total UPF1, as determined by Fisher's exact test.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "C Heat map of changes in relative mRNA abundance for genes encoding NMD factors, as determined from RNA-seq  following transfection of HEK-293 cells with a siRNA that targets both UPF1  isoforms (UPF1total) or a siRNA that specifically targets the UPF1LL isoform.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "D Density plot of changes in relative mRNA abundance as determined by RNA-seq in SMG7ko/SMG6kd cells, relative to a parental cell line treated with control siRNAs Genes were categorized as up-regulated by siUPF1total only, siUPF1LL only, or both siUPF1total and siUPF1LL. Statistical significance was determined by K-W test, with Dunn's correction for multiple comparisons.",
    "ncbi_link": "SMG6: 23293
SMG7: 9887
UPF1: 5976"
  },
  {
    "caption": "F Gene ontology analysis of 1621 genes that increased in expression at least 1.4-fold upon UPF1LL-specific knockdown in HEK-293 cells under normal cellular conditions. Genes may map to multiple categories.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "E RT-qPCR analysis of indicated transcripts from CLIP-UPF1 overexpression RNA-seq experiments. Relative fold changes are in reference to the GFP expressing control line. Significance of CLIP-UPF1SL or CLIP-UPF1LL overexpression was compared to the GFP expressing control line. Asterisk (*) indicates P < 0.05, as determined by two-way ANOVA. Black dots represent individual data points and error bars indicate mean±SD (n = 3 biological replicates). Dashed lines indicate log2(fold change) of ±0.5. For protected mRNAs, the motif density of PTBP1/hnRNP L within the 3'UTR is indicated. PTC+ indicates the use of primers specific to transcript isoforms with validated poison exons",
    "ncbi_link": "CLIP: 
GFP: 
UPF1: 5976"
  },
  {
    "caption": "A Semiquantitative RT-PCR of UPF1SL or UPF1LL transcript levels following transfection of HEK-293 cells with the indicated siRNAs.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "B RT-qPCR  analysis of indicated transcripts following transfection of a NT siRNA or SRSF1-specific siRNA under conditions of CLIP-UPF1SL or CLIP-UPF1LL overexpression. Relative fold changes are in reference to the GFP expressing control line treated with a NT siRNA. Asterisk (*) indicates P < 0.05, as determined by unpaired Student's t-test. Black dots represent individual data points and error bars indicate mean±SD (n = 3 biological replicates).",
    "ncbi_link": "CLIP: 
GFP: 
SRSF1: 6426
UPF1: 5976"
  },
  {
    "caption": "C Density plot of changes in relative mRNA abundance as determined by RNA-seq following SRSF1 overexpression Genes were categorized as up-regulated by siUPF1total only, siUPF1LL only, or both siUPF1total and siUPF1LL. Statistical significance was determined by K-W test, with Dunn's correction for multiple comparisons.",
    "ncbi_link": "SRSF1: 6426
UPF1: 5976"
  },
  {
    "caption": "B Density plots of changes in relative mRNA abundance as determined by RNA-seq following treatment of  HEK-293  cells with 1 µM thapsigargin for 6hr (left) or 9hr (right). Genes were categorized as up-regulated by siUPF1total only or siUPF1LL only under basal conditions. Statistical significance was determined by K-W test, with Dunn's correction for multiple comparisons.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "A mRNA decay  measurement using Roadblock-qPCR RNA was isolated from HEK-293 cells at indicated timepoints following transfection with indicated siRNAs and treatment with 400 µM 4sU and 50 µg/mL puromycin.  mRNA half-lives were estimated by fitting the data to a single-phase exponential decay model. Puromycin treatment was compared to the vehicle control and siUPF1LL was compared to the siNT in the absence and presence of puromycin treatment using the extra-sum-of-squares F test. Error bars indicate mean±SD (n = 4 biological replicates).",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "C Density plot of changes in relative mRNA abundance as determined from RNA-seq  following treatment of HEK-293 cells with 50 µg/mL of puromycin for 4hr. mRNAs were subdivided by PTBP1 and/or  hnRNP L motif density within the first 400 nt of 3'UTR. Statistical significance was determined by K-W test, with Dunn's correction for multiple comparisons. D Density plot as in (C), following  UPF1LL-specific knockdown.",
    "ncbi_link": "UPF1: 5976"
  },
  {
    "caption": "B, RMD assays performed after DSBs have been generated by sgRNAs/Cas9. The distance between the sgRNA/Cas9 cleavage sites and the repeat sequences is indicated. U2OS cells carrying a single copy of the EGFP-SSA reporter (3427-17) were transfected with sgRNA/Cas9 plasmids, and the percentage of GFP-positive cells was determined (left). U2OS cells transfected with the indicated reporters EGFP-SSA-17/6 bp, EGFP-SSA-0.3 kb, EGFP-SSA-0.6 kb and EGFP-SSA-1.0 kb were pooled as a population after selection of the drug marker on the reporters, followed by sgRNA/Cas9 cleavage (right).",
    "ncbi_link": "EGFP: 
GFP: 
Cas9: 57852564"
  },
  {
    "caption": "C, RMD is strongly induced when a DSB is generated close to one repeat. The U2OS (EGFP-SSA-3427-17) cell line carrying a single copy of the reporter was transfected with sgRNA/Cas9 plasmids as indicated, and the percentage of GFP-positive cells was determined.",
    "ncbi_link": "EGFP: 
GFP: 
Cas9: 57852564"
  },
  {
    "caption": "Determination of RMD frequency in U2OS (EGFP-SSA-3427-17) cells when POLD3 is depleted by lentiviral expression of shRNA. Cells infected with a lentiviral empty vector were used as control. The knockdown level of the indicated proteins was shown by Western blot, using KU70 as the loading control.",
    "ncbi_link": "EGFP: 
POLD3: 10714"
  },
  {
    "caption": "Determination of RMD frequency in U2OS (EGFP-SSA-3427-17) cells when RAD52 is depleted by lentiviral expression of shRNA. Cells infected with a lentiviral empty vector were used as control. The knockdown level of the indicated proteins was shown by Western blot, using KU70 as the loading control.",
    "ncbi_link": "EGFP: 
RAD52: 5893"
  },
  {
    "caption": "G, Determination of RMD frequency in U2OS (EGFP-SSA-3427-17) cells when RAD51 is depleted by lentiviral expression of shRNA. Cells infected with a lentiviral empty vector were used as control. The knockdown level of the indicated proteins was shown by Western blot, using KU70 as the loading control.",
    "ncbi_link": "EGFP: 
RAD51: 5888"
  },
  {
    "caption": "B, RMD efficiency is decreased when the distance from a DSB to one repeat is increased. RMD assays were performed in U2OS (EGFP-SSA-3427-17) cells using the indicated sgRNAs/Cas9. The distance between the sgRNA/Cas9 cleavage sites and the repeat sequences is shown.",
    "ncbi_link": "EGFP: 
Cas9: 57852564"
  },
  {
    "caption": "C and D, Knockdown of POLD3 impairs RMD when a DSB is close to one repeat. RMD frequency was determined in U2OS (EGFP-SSA-3427-17) cells using the indicated sgRNAs/Cas9 with or without depletion of POLD3 by lentivirus-expressed shRNA. Cells infected with a lentiviral empty vector were used as control. The distance between the sgRNA/Cas9 cleavage sites and the repeat sequences is indicated. The knockdown level of POLD3 was shown by Western blot, and KU70 was used as the loading control.",
    "ncbi_link": "EGFP: 
Cas9: 57852564
POLD3: 10714"
  },
  {
    "caption": "A, Cyclin E overexpression results in increased RMD when the DSB is close to one repeat. The U2OS (EGFP-SSA-3427-3) cell line carrying Tet-on-cyclin E plasmid was used, and RMD frequency was determined with or without induction of cyclin E expression by doxycycline (DOX, 0.5 µg/mL), which was added 24 hours before transfection of the indicated sgRNAs/Cas9. Cyclin E expression levels were validated by Western blot, using KU70 as the loading control.",
    "ncbi_link": "EGFP: 
Cas9: 57852564
cyclin E: 9134///898"
  },
  {
    "caption": "B, ATR is required for BIR/RMD upon cyclin E overexpression. RMD frequency was determined in U2OS (EGFP-SSA-3427-3) cells infected with lentivirus-expressed ATR shRNA or the control vector (Ctrl) with and without induction of cyclin E expression by DOX (0.5 µg/ml) after R29 sgRNA/Cas9 cleavage. ATR knockdown was shown by Western blot with KU70 as the loading control.",
    "ncbi_link": "EGFP: 
ATR: 545
Cas9: 57852564
cyclin E: 9134///898"
  },
  {
    "caption": "D, RMD is stimulated when Cas9-D10A is used to create a nick near the repeat. The repair frequencies of the U2OS (MMEJ) reporter cell line (left) and U2OS (EGFP-SSA-3427-17) cell line (right) were determined after expression of the indicated sgRNAs/Cas9 and sgRNAs/Cas9-D10A. The distance between the sgRNA cleavage sites and the left and right repeat sequences is indicated (right bottom).",
    "ncbi_link": "EGFP: 
Cas9: 57852564"
  },
  {
    "caption": "E, RMD induced by Cas9-D10A is dependent on POLD3. U2OS (EGFP-SSA-3427-17) cells were infected with lentiviruses expressing shRNA for POLD3 or vector control and RMD was determined after cleavage by the indicated sgRNAs/Cas9-D10A. The distance between sgRNA/Cas9-D10A cleavage sites and the left and right repeat sequences is indicated at the bottom. The knockdown level of POLD3 was shown by Western blot, and KU70 was used as the loading control.",
    "ncbi_link": "EGFP: 
Cas9: 57852564
POLD3: 10714"
  },
  {
    "caption": "F, p27 suppresses BIR/RMD and SSA/RMD. U2OS (EGFP-SSA-3427-3) cells carrying the Tet-on-cyclin E allele were infected with and without p27 lentiviral viruses. RMD was determined before and after induction of cyclin E overexpression by DOX (0.5 µg/mL) added 24 hours before transfection with the indicated sgRNAs/Cas9. Cyclin E expression levels and cell cycle profiles are shown in Appendix Fig S6.",
    "ncbi_link": "EGFP: 
Cas9: 57852564
cyclin E: 9134///898
Cyclin E: 9134///898
p27: 1027"
  },
  {
    "caption": "B, Impact of the 5' DSB/repeat distance on RMD frequency when the 3' DSB/repeat distance is fixed. RMD assays were performed using mES cells carrying the RMD-GFP reporter, and RMD frequency was determined by the number of GFP+ cells normalized to transfection efficiency. The distance between the sgRNA targeting sites and the repeats is indicated.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "C, Long-range RMD is dependent on POLD3 when one DSB is close to a repeat. mES cells carrying the RMD-GFP reporter were transfected with nontargeting siRNA (Ctrl) or a pool of POLD3 siRNAs (siPOLD3) 24 hours before for the first time, and with transfection of sgRNAs/Cas9 the second time. The graphs show the frequency of GFP+ cells normalized to the transfection efficiency. The distance between the sgRNA targeting sites and the repeats is indicated.",
    "ncbi_link": "GFP: 
Cas9: 57852564
POLD3: 67967"
  },
  {
    "caption": "D and E, Impact of the 3' DSB/repeat distance on RMD frequency when the 5' DSB/repeat distance is fixed. RMD assays were performed using mES cells carrying the RMD-GFP reporter, and RMD frequency was determined by the number of GFP+ cells normalized to transfection efficiency. The distance between the sgRNA targeting sites and the repeats is indicated.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "F, RMD frequency of two far-apart repeats that are a short distance from the DSB. RMD was determined in mES cells carrying the RMD-GFP reporter using the indicated sgRNAs/Cas9, with the frequency of GFP+ cells normalized to transfection efficiency. The distance between the sgRNA targeting sites and the repeats is indicated.",
    "ncbi_link": "GFP: 
Cas9: 57852564"
  },
  {
    "caption": "G, The roles of POLD3, RAD51 and RAD52 in RMD of two far-apart repeats that are a short distance from the DSB. RMD was determined in mES cells carrying the RMD-GFP reporter using the indicated sgRNAs/Cas9 after POLD3 (left) or RAD51 (middle) was depleted by siRNA or RAD52 was knocked out (right). The distance between the sgRNA targeting sites and the repeats is indicated.",
    "ncbi_link": "GFP: 
Cas9: 57852564
POLD3: 67967
RAD51: 19361
RAD52: 19365"
  },
  {
    "caption": "SSA/RMD and BIR/SSA are both dependent on ATM. SSA/RMD and BIR/SSA frequencies in U2OS (EGFP-SSA-3427-17) cells were determined after the addition of ATM inhibitor (20mM ku55933) or DMSO to the cell culture medium 24 hours before transfection of the indicated sgRNA/Cas9",
    "ncbi_link": "EGFP: 
Cas9: 57852564"
  },
  {
    "caption": "BIR/SSA are both dependent on ATM. BIR/RMD in mES cells carrying the RMD-GFP reporter were determined after the addition of ATM inhibitor (20mM ku55933) or DMSO to the cell culture medium 24 hours before transfection of the indicated sgRNA/Cas9 or in ATM KO mES cells carrying the RMD-GFP reporter (right).",
    "ncbi_link": "GFP: 
Cas9: 57852564"
  },
  {
    "caption": "Dependence of RMD on H2AX. SSA/RMD and BIR/RMD frequencies in U2OS (EGFP-SSA-3427-17) cells were determined using the indicated sgRNA/Cas9 after depletion of H2AX by lentivirus expressed shRNA Depletion of H2AX by shRNA in was determined by qPCR",
    "ncbi_link": "EGFP: 
Cas9: 57852564
H2AX: 15270"
  },
  {
    "caption": "D, Dependence of RMD on H2AX. BIR/RMD in mES cells carrying the RMD-GFP reporter , or by transfection with H2AX siRNA or in RAD52 KO cells",
    "ncbi_link": "GFP: 
H2AX: 15270
RAD52: 19365"
  },
  {
    "caption": "A, Frequency of long-range RMD is increased by an additional DSB downstream of the 3' repeat. Illustrations show the GFP-RMD reporter, with sgRNAs/Cas9 cleavage sites indicated as red arrows (left). The frequency of BIR/SSA in mES cells carrying the RMD-GFP reporter was determined after cleavage of the reporter by the indicated sgRNAs/Cas9 (right).",
    "ncbi_link": "GFP: 
Cas9: 57852564"
  },
  {
    "caption": "B and C, The effects of RAD52, POLD3, ATM and H2AX inactivation on BIR/RMD with cleavage at L17/D10k. The frequency of BIR/RMD in mES cells carrying the RMD-GFP reporter was determined using the sgRNAs/Cas9 at L17/D10k in RAD52 KO cells or after POLD3 depletion by siRNA (B), or after treatment with ATM inhibitor (ku55933, 15mM) or H2AX depletion by siRNA (C).",
    "ncbi_link": "GFP: 
Cas9: 57852564
H2AX: 15270
POLD3: 67967
RAD52: 19365"
  },
  {
    "caption": "A, Long-range BIR/RMD with identical repeats or divergent repeats. The frequency of BIR/RMD in mES cells carrying the RMD-GFP reporter with identical repeats (0%) or repeats with 1% and 3% divergence was determined after cleavage at L17/R3.3k or L17/R28.4k.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "B and C, The effect of MSH2 on BIR/RMD when repeat sequences are divergent. The frequency of BIR/RMD was determined after cleavage at L17/R3.3k or L17/R28.4k in mES cells carrying the RMD-GFP reporter with 1% and 3% divergent repeats, and with and without MSH2 KO (B) or with MSH2 KO and POLD3 depletion by siRNAs (C). The MSH2 KO was validated by Western blot, using KU70 as the loading control as shown in (B). Data information: Error bars represent standard deviation (SD) of at least three independent experiments. *P < 0.05, **P < 0.01, two-tailed non-paired t-test. ",
    "ncbi_link": "GFP: 
MSH2: 17685
POLD3: 10714"
  },
  {
    "caption": "B Effect of Gli1ZF mutants on the binding affinity to DNA as predicted by in silico alanine scanning. The ∆∆G was calculated along MD trajectories as the difference between the ∆G of each Gli1ZF alanine mutant and Gli1ZF‐WT. Results are shown as ∆∆G values in kcal/mol calculated by means of the MM‐PBSA methods ± SEM.",
    "ncbi_link": "Gli1: 2735"
  },
  {
    "caption": "C Effect of Gli1ZF mutants on Gli1‐dependent transcriptional activation. Luciferase assay was performed in HEK293T cells transfected with 12XGliBS‐Luc (GliBS, Gli binding site), pRL‐TK Renilla (normalization control), Flag‐Gli1 WT or the indicated Flag‐Gli1 mutants. Data show the mean ± SD of three independent experiments. *P 0.01; **P 0.05 versus Gli1 WT. Western blot analysis of Flag‐Gli1 WT or the indicated Flag‐Gli1 mutant expression levels (bottom panel).",
    "ncbi_link": "Luc: 
Renilla: 
Gli1: 2735"
  },
  {
    "caption": "E Gli1/DNA binding. Double‐stranded oligonucleotide containing the canonical GliBS sequence (5′-TTGCCTACCTGGGTGGTCTCTCCACTT-3′) or mutated GliBS sequence used as control (5′-TTGCCTACCTCCCACTTCTCTCCACTT-3′) was used as probe (P) in EMSA experiments. The assay was performed using recombinant GST‐Gli1ZF‐WT (Gli1 zinc finger fragment: aa 242-424), GST‐Gli1ZF‐K350A and GST‐Gli1ZF‐K340A. The graph on the right indicates ratio (mean arbitrary units ± SD from three independent experiments) of GST‐Gli1ZF‐WT or GST‐Gli1ZF mutants bound to the labeled GliBS probe/GliBS‐free probe normalized to the amount of GST‐Gli1ZF‐WT/DNA binding (as described in ). *P 0.05 versus Gli1 WT.",
    "ncbi_link": "Gli1: 2735"
  },
  {
    "caption": "A Inhibition of Gli1‐induced transcription in transfected HEK293T cells. HEK293T cells were transfected with 12XGliBS‐Luc and pRL‐TK Renilla (normalization control) plus control (empty) or Gli1 vector and treated with increasing concentrations of GlaB or GANT61. Treatment time was 24 h, and control cells were treated with DMSO only.",
    "ncbi_link": "Luc: 
Renilla: "
  },
  {
    "caption": "C Inhibition of Gli1‐induced transcription in transfected Smo−/−MEF cells. Smo−/−MEF cells were transfected with 12XGliBS‐Luc and pRL‐TK Renilla (normalization control) plus control (empty) or Gli1 vector and treated for 24 h with increasing concentrations of GlaB or DMSO only as control.",
    "ncbi_link": "Luc: 
Renilla: 
Smo: 319757"
  },
  {
    "caption": "D The graphs show the Hh target gene expression levels in Ptch1−/−MEFs treated for 48 h with GlaB and DMSO as a control. mRNA levels were determined by quantitative real‐time PCR (qRT-PCR) normalized to endogenous control (β2‐microglobulin and HPRT). Pfkfb3 gene was used as a negative control.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Pfkfb3: 170768
Ptch1: 19206"
  },
  {
    "caption": "F SuFu−/−MEFs were treated for 48 h with GlaB and DMSO as a control. Gli1 and Ptch1mRNA levels were determined by qRT-PCR normalized to β2‐microglobulin and HPRT expression. Pfkfb3 gene was used as a negative control.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Gli1: 14632
Pfkfb3: 170768
Ptch1: 19206
SuFu: 24069"
  },
  {
    "caption": "Promoter occupancy of Gli1 is prevented by GlaB treatment. MEF WT cells were transfected with Flag‐tagged Gli1 or empty vectors, and chromatin immunoprecipitation (ChIP) was carried out. qRT-PCR was performed using primers encompassing the Gli‐BS of mouse Ptch1 promoter (right, schematic representation). Results are indicated as fold difference, relative to empty (pcDNA3) control.",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "H Ptch1 mRNA expression levels (left panel) were determined by qRT-PCR in Daoy cells transfected with siRNA specific for Gli1 and Gli2 (siGli1/2) or a non‐specific control siRNA (siCtr) and treated for 24 h with GlaB or DMSO as a control. (right panel) The graph shows Gli1 and Gli2mRNA expression levels determined by qRT-PCR in Daoy cells transfected with siGli1/2 or siCtr. Results are expressed as fold repression relative to control, and data were normalized to GAPDH and HPRT expression.",
    "ncbi_link": "GAPDH: 
HPRT: 
Gli1: 2735
Gli2: 2736
Ptch1: 5727"
  },
  {
    "caption": "B Detail of GlaB binding to Gli1ZF‐WT, Gli1ZF‐K340A, GLI1ZF‐K350A, GLI1ZF‐K340A/K350A mutants and respective theoretical affinity values. Gli1 is shown as blue transparent surface; K340 and K350 are colored magenta. GlaB is shown as green sticks.",
    "ncbi_link": "Gli1: 2735"
  },
  {
    "caption": "C Inhibition of Gli1/DNA binding by GlaB. EMSA using recombinant GST‐Gli1ZF‐WT or GST‐Gli1ZF‐K340A in the presence of different concentrations of GlaB or with DMSO only. The shifted complex is competed with a 50× excess of cold probe. The graph on the right indicates ratio (mean arbitrary units ± SD from three independent experiments) of GST‐Gli1ZF‐WT or GST‐Gli1ZF‐K340A bound to the labeled GliBS probe/GliBS‐free probe normalized to the amount of GST‐Gli1ZF‐WT/DNA binding in absence of GlaB. *P 0.05 versus DMSO; **P 0.05 K340A + GlaB versus Gli1 WT + GlaB.",
    "ncbi_link": "Gli1: 2735"
  },
  {
    "caption": "D HEK293T cells were transfected with 12XGliBS‐Luc and pRL‐TK Renilla (normalization control) plus control (empty vector) or Gli1 or Gli1K340A mutant and treated with increasing concentrations of GlaB. Treatment time was 24 h, and control cells were treated with DMSO only. Data show the mean ± SD of three independent experiments. *P 0.05 versus DMSO; **P 0.05 K340A versus Gli1 WT.",
    "ncbi_link": "Luc: 
Renilla: 
Gli1: 2735"
  },
  {
    "caption": "E qRT-PCR and show Hh and proliferation target mRNA and protein expression levels determined in ex vivo GCP culture derived from 6‐day‐old mousecerebella after s.c. injections of GlaB. In all qRT-PCR experiments, the results were normalized to endogenous control (β2‐microglobulin and HPRT). *P 0.05 versus Ctr.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: "
  },
  {
    "caption": "A, B Ex vivo cell cultures from Ptch1+/−mice MBs were treated with GlaB (5 μM), GANT61 (10 μM) or DMSO only. After the indicated times, a trypan blue count was performed (A) to determine the growth rate of viable cells.",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "A, B Ex vivo cell cultures from Ptch1+/−miceMBs were treated with GlaB (5 μM), GANT61 (10 μM) or DMSO only. After the indicated times, Gli1 mRNA expression levels were determined by qRT-PCR (B) normalized to endogenous control (β2‐microglobulin and HPRT).",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Gli1: 14632
Ptch1: 19206"
  },
  {
    "caption": "C-F GlaB inhibits MB‐SCs' self‐renewal and proliferation. (C) Suspension of single MB‐SCs isolated from Ptch1+/−mice. MBs were cultured in stem cell medium to allow the formation of primary neurospheres. Primary neurospheres were dissociated and treated with increasing concentrations of GlaB or DMSO only. After 7 days of treatment, the number of secondary neurospheres derived from a known number of single cells was counted. The self‐renewal MB‐SCs' capability is expressed as percentage of neurosphere‐forming cells (left). Representative bright field images of tumor neurospheres after GlaB treatment are also shown (right).",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "C-F GlaB inhibits MB‐SCs' self‐renewal and proliferation. (D, E) MB‐SCs isolated from Ptch1+/−miceMBs were treated for 48 h with GlaB (5 μM) or DMSO only. qRT-PCR analysis show Hh, proliferation and stemness target mRNA expression levels. For qRT-PCR, results were normalized to endogenous control (β2‐microglobulin and HPRT).",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Ptch1: 19206"
  },
  {
    "caption": "C-F GlaB inhibits MB‐SCs' self‐renewal and proliferation. (D, E) MB‐SCs isolated from Ptch1+/−miceMBs were treated for 48 h with GlaB (5 μM) or DMSO only. Western blot analysis show Hh, proliferation and stemness target protein expression levels.",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "G TUNEL assay in MB‐SCs. MB‐SCs isolated from Ptch1+/−miceMBs were treated with GlaB (5 μM) and compared to DMSO‐treated sample. Bottom panel shows a Western blot of caspase‐3 in GlaB‐treated versus control cells.",
    "ncbi_link": "Ptch1: 19206"
  },
  {
    "caption": "E qRT-PCR analysis show Hh and proliferation target mRNA expression levels. For qRT-PCR, results were normalized to endogenous control (β2‐microglobulin and HPRT). Data show the mean ± SD of tumor (n = 6) for each treatment. *P 0.05 versus Ctr.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: "
  },
  {
    "caption": "C Gli1 mRNA expression levels were determined by qRT-PCR after treatment of ASZ001 BCC cells with GlaB or DMSO only for the indicated times. Results were normalized to endogenous control (β2‐microglobulin and HPRT). Data show the mean ± SD of three independent experiments. *P 0.05 versus DMSO.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Gli1: 14632"
  },
  {
    "caption": "D-H GlaB inhibits Gli1‐dependent BCC tumor growth in ASZ001 BCC allografts in vivo. (H) qRT-PCR of Hh and proliferation target mRNA expression levels. Results were normalized to endogenous control (β2‐microglobulin and HPRT). Shown is the mean ± SD of tumor (n = 6) for each treatment. *P 0.05 versus Ctr.",
    "ncbi_link": "HPRT: 
β2‐microglobulin: 
Gli1: 14632"
  },
  {
    "caption": "(A) WT and CITK -/- embryonic (E14.5) mousecerebral cortex was stained for γ-tubulin (green) and DNA (gray). The ventricular plane is marked by a red dashed line, and the spindle axis of apical progenitors is indicated by a white dashed line. The angle between these two lines represents the mitotic angle. Scale bars = 5 μm.(B) Quantification of vertical divisions of apical progenitors in WT and CITK -/- mice. n= 3 per each genotype.",
    "ncbi_link": "CITK: 12704"
  },
  {
    "caption": "(C) Pregnant CITK +/- females, crossed with CITK +/- males, were injected with BrdU at E13.5; 24 hours later (E14.5) WT and CITK -/- embryonic mouse cerebral cortex were fixed in 4% PFA, cryosectioned and stained for Ki67 (red), BrdU (green), Tbr2 (blue) and DAPI (gray). The different cortical regions are indicated: CP=cortical plate; IZ= intermediate zone; SVZ= subventricular zone; VZ= ventricular zone. Scale bars = 10 μm. White arrows in the inset indicate two Ki67- cells positive for BrdU and Tbr2.",
    "ncbi_link": "CITK: 12704"
  },
  {
    "caption": "(G) Neuroblasts of wild type and dck alleles immunostained for α-tubulin and Miranda. Note that whereas in wild type cells there is a tight coupling of the mitotic spindle with the polarity axis, in dck alleles the spindle show a more oblique orientation respect to Mira crescent. Scale bar = 5 μm.(H) Distribution of spindle angle amplitude (°) in neuroblasts of wild type and ck alleles (n=58).",
    "ncbi_link": "dck: 39429"
  },
  {
    "caption": "(A) Selected frames from time-lapse imaging experiments (see Movies EV1 and EV2) showing two dividing cells transfected with either control (CTRL) or CITK-specific siRNAs, respectively. Note one of the two daughter cells in the lower panel (red arrow) going out of focus as a consequence of oblique division.(B) Graphical representation of vertical and oblique divisions. The cleavage plane is indicated by a black dashed line.(C) Quantification of divisions showing uneven timing of daughter cell flattening onto the substrate after mitosis (oblique division) in CITK siRNA treated HeLa cells compared to control (n > 50 cells, 3 independent experiments).",
    "ncbi_link": "CITK: 11113"
  },
  {
    "caption": "(D) Control or CITK-depleted cells were immunostained for γ-tubulin (red) and DNA (blue) and imaged in z (0.3 µm-thick sections). Upper panel: maximum intensity projections of confocal z-stacks are shown. Lower panel: cross-section (XZ) through the two poles of the same cell.(E) Distribution of spindle angles (°) in control and in CITK-depleted cells. The values represent the angles between the axis crossing the two poles of metaphase spindles and the coverslip. (n ≥ 150 cells, 6 independent experiments).",
    "ncbi_link": "CITK: 11113"
  },
  {
    "caption": "(F) Quantification of spindle angles average in control cells and in cells depleted of CITK, ASPM or co-depleted of the two proteins (n ≥ 150 cells, in at least 3 independent experiments).",
    "ncbi_link": "ASPM: 259266
CITK: 11113"
  },
  {
    "caption": "(G) Control or CITK-depleted cells immunostained for ASPM (green), γ-tubulin (red) and DNA (blue).",
    "ncbi_link": "CITK: 11113"
  },
  {
    "caption": "(H) Control or ASPM-depleted cells treated as in (A) and immunostained for CITK (green), γ-tubulin (red) and DNA (blue).(I) Quantification of CITK positive centrosomes and of the ratio of CITKspindle pole intensity versus total cell mean intensity, in control and ASPM-depleted cells. (n ≥ 75 cells, 4 independent experiments).",
    "ncbi_link": "ASPM: 259266"
  },
  {
    "caption": "(A) Control, CITK or ASPM-depleted HeLa cells immunostained for α-tubulin (red) and DNA (blue). Maximum intensity projections of confocal z-stacks are shown.(B) Quantification of astral MT number and maximal length in HeLa cells transfected with CTRL, CITK or ASPM siRNA (n > 130 cells in 3 independent experiments).",
    "ncbi_link": "ASPM: 259266
CITK: 11113"
  },
  {
    "caption": "(C) Quantification of the rescue of astral MT number after CITK overexpression in ASPM-depleted HeLa cells (n > 50 cells in 3 independent experiments).(D) Quantification of spindle orientation rescue after overexpression of CITK, CITN (lacking the kinase domain) or CKD (Citron kinase dead) mutants in ASPM-depleted HeLa cells (n > 50 cells in 3 independent experiments).",
    "ncbi_link": "ASPM: 259266
CITK: 11113"
  },
  {
    "caption": "(E) Synchronized HeLa transfected with control, ASPM- or CITK-specific siRNAs treated with DMSO or with 250 pM Paclitaxel (taxol) 30 min before immunostaining for α-Tubulin. Spindle angles were measured as above (n > 100 cells in 6 independent experiments).",
    "ncbi_link": "ASPM: 259266
CITK: 11113"
  },
  {
    "caption": "(B) Kymographs of pole (bottom)-to-cortex (top) line scans of control and CITK-depleted EB3-tdTomatoHeLa cells. The maximum projection of a 20-pixel-wide line (exemplified above) was plotted at 500 ms time intervals from left to right. MT growth results in diagonal lines.",
    "ncbi_link": "CITK: 11113"
  },
  {
    "caption": "(D) Immunofluorescence microscopy images showing MT growth at mitotic spindle poles 0, 1, and 2 min after nocodazole washout. Control and CITK-depleted cells were immunostained for α-tubulin (red) and DNA (blue).(E) Percentage of cells showing detectable MT nucleation (aster size > 1 µm) 0, 1, and 2 min after nocodazole washout (n > 100 cells, 4 independent experiments).(F) Quantification of aster size 2 min after nocodazole washout (n > 100 cells, 4 independent experiments).",
    "ncbi_link": "CITK: 11113"
  },
  {
    "caption": "(f) A549-ACE2 or control A549-Venus cells were pretreated with Tubercidin or vehicle (DMSO) 3h prior to infection with SARS-CoV-2 at MOI 0.1. After 24 hours, abundances of SARS-CoV-2 nucleoprotein (N), ACE2, Venus and β-actin (ACTB, loading control) were visualized using Western blotting. Presented data is representative of 3 independent repeats.",
    "ncbi_link": "Venus: 
ACE2: 59272"
  },
  {
    "caption": "Mass spectrometry based analysis of cells treated with DZNep and infected with SARS-CoV-2 and SARS-CoV. (c) Donor-normalized LFQ abundances of viral nucleoprotein (N) and spike (S) in the indicated conditions. Error bars represent mean +/- sd of n=4 donors (NHBE) or n=4 independently infected A549-ACE2 cultures. Statistics were calculated using Student's two-sided t-test as indicated.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "(E) LC3-RFP expression in control (ctrl) and Rb−/− myotubes. Insets show nuclear DAPI stain (blue).",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(G) Representative Western blot for LC3 in E16.5 control and mgRb:Rb−/− muscles. (H) Quantification of LC3-II/tubulin ratio in E16.5 mgRb:Rb−/− skeletal muscles relative to control as depicted in G (mean ± SD; n = 3). *, P = 0.016 by Student's t test.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(I) Representative Western blot for LC3-I and LC3-II expression in whole cell lysates from the indicated myotubes transduced with Ad.GFP or Ad.RbΔK11. (J) Quantification of LC3-II/tubulin ratio by Western blots as shown in I. Data represent mean ± SD (n = 7). *, P = 0.047; **, P = 0.005 by analysis of variance.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(C) MitoTracker (red) and LC3immunostaining (green) of myotubes at DM-2. Chloroquine and 3-MA (where indicated) were added 12 h before staining. Note the extensive overlap of MitoTracker and LC3 in Rb−/−myotubes (yellow), which is inhibited by 3-MA. (D) Mean percentage of MitoTracker (red) to LC3 (green) overlap in 25 myotubes from two independent cultures in control versus Rb−/−myotubes (total) or Rb−/−myotubes with perinuclear mitochondrial aggregation (high). *, P = 7 × 10−5 by Student's t test.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(A) Mean number of myotubes per field in indicated myoblast cultures induced to differentiate after transduction with Ad.GFP or Ad.Bcl-2. Each point represents the mean ± SD of six fields from six independent experiments. Bcl-2-rescued, twitching Rb−/− myotubes are shown in Video 2. (inset) Western blot for Bcl-2 in Ad.Bcl2-transduced versus uninfected primary myoblasts.",
    "ncbi_link": "Bcl-2: 12043
Rb: 19645"
  },
  {
    "caption": "(B) Immunostaining for MCK (green) in Ad.Bcl-2-transduced control (ctrl) and Rb−/− myotubes at DM-6.",
    "ncbi_link": "Bcl-2: 12043
Rb: 19645"
  },
  {
    "caption": "(C) Western blot for MCK, myogenin, MHC, and troponin T in indicated cultures at DM-6 after transduction with Ad.Bcl-2. Tubulin was used as a loading control. Black lines indicate that intervening lanes have been spliced out.",
    "ncbi_link": "Bcl-2: 12043"
  },
  {
    "caption": "(D) Mean number of Rb−/− myotubes after 3-MA treatment, bezafibrate, or DMSO/vehicle as indicated. Counts are mean ± SD of six fields (n = 4).",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(E, left and middle) Brightfield images of the indicated myotubes treated or not with 3-MA at DM-8. (right) Immunostaining for MHC (red) at DM-14 in the presence of 3-MA. Arrowheads label 3-MA-rescued Rb−/− myotubes at DM-8. 3-MA-rescued, twitching Rb−/− myotubes are shown in Video 4.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(F) Immunostaining for BrdU (green) and MHC (red) of 3-MA-treated cultures at DM-2 or DM-10. Rb−/− myotubes incorporated BrdU at DM-2 (arrowheads) but not DM-10.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(G) Brightfield images (left and middle) and MHC staining (right) of the indicated cultures treated or not with bezafibrate. Arrowheads point to bezafibrate-rescued Rb−/− myotubes.",
    "ncbi_link": "Rb: 19645"
  },
  {
    "caption": "(C) Rbf/f myoblasts transduced with Ad.GFP or Ad.Cre and immunoblotted for pRb. Tubulin was used as a loading control.",
    "ncbi_link": "Cre: 
Rb: 19645"
  },
  {
    "caption": "(D) Rbf/f myoblasts transduced with Ad.GFP or Ad.Cre and immunostained for pRb (red). (insets) DAPI staining for nuclei (blue).",
    "ncbi_link": "Cre: 
Rb: 19645"
  },
  {
    "caption": "(E) Immunostaining for MHC in Rbf/f myoblasts transduced with Ad.Cre and induced to differentiate in normoxia (top and middle) or hypoxia (bottom).",
    "ncbi_link": "Cre: 
Rb: 19645"
  },
  {
    "caption": "(F, top) Brightfield images of Rbf/f myoblasts transduced with Ad.EV or Ad.Cre and induced to differentiate under hypoxia. (bottom) Larger view of the boxed field. Arrowheads point to rescued Rb−/− myotubes. This field is shown in Video 6.",
    "ncbi_link": "Cre: 
EV: 
Rb: 19645"
  },
  {
    "caption": "(G) Quantification of myotube formation in Rbf/f myoblasts transduced with Ad.EV or Ad.Cre and induced to differentiate under hypoxia. Counts are mean of six representative fields (n = 3). *, P = 0.004.",
    "ncbi_link": "Cre: 
EV: 
Rb: 19645"
  },
  {
    "caption": "(I) MHC staining (red) of the indicated myoblasts transduced with Ad.NF-κB/HIF-1α and induced to differentiate in normoxia.",
    "ncbi_link": "HIF-1α: 15251
NF-κB: 18033"
  },
  {
    "caption": "(J) Quantification of myotube formation in the indicated myoblasts transduced with Ad.EV or Ad.NF-κB/HIF-1α and induced to differentiate in normoxia. Myotube counts are the mean of six fields (n = 3). Error bars represent SD.",
    "ncbi_link": "EV: 
HIF-1α: 15251
NF-κB: 18033"
  },
  {
    "caption": "The relative expression of ADAR1 p150 mRNA (B) and total ADAR1 mRNA (C) in sorted DN, DP, 4SP and 8SP thymocytes isolated from WT mice. The relative expression of ADAR1 p150 mRNA (B) and total ADAR1 mRNA (C) were normalized to the level of expression in DN thymocytes (DN values set to 1). Values represent the relative gene expression normalized to GAPDH mRNA and are displayed as the mean ± SEM (n = 5; Mann-Whitney U-test, *p < 0.05, **p < 0.01).",
    "ncbi_link": "GAPDH: 
ADAR1 p150: 56417
ADAR1: 56417"
  },
  {
    "caption": "The relative expression of type I interferon-stimulated genes (ISGs) in sorted DN, DP, 4SP and 8SP thymocytes isolated from WT mice. Values represent the relative gene expression normalized to GAPDH mRNA and are displayed as the mean ± SEM (n = 3; Mann-Whitney U-test, *p < 0.05). The relative expression of ISGs was normalized against the level of expression in DN thymocytes (DN values set to 1).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "Total number of thymocytes in wild-type (WT) and CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice.",
    "ncbi_link": "Adar1: 56417
A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-CD4 and anti-CD8 antibodies and analyzed by flow cytometry. Representative images are shown (B).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "The percentages of DN, DP, 4SP, and 8SP thymocytes were compared between WT and Cd4cre A1fl/fl mice (C).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-CD4, anti-CD8 and anti-TCRβ antibodies and were gated by the high expression of TCRβ (TCRβhigh). Representative images are shown (D).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "The percentages of DN, DP, 4SP, and 8SP thymocytes were compared between WT and Cd4cre A1fl/fl mice (E).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-CD4, anti-CD8, anti-CD69 and anti-MHC-I antibodies and were gated on 4SP thymocytes. Representative images are shown (upper panel). The percentages of CD69+MHC-I- (SM), CD69+MHC-I+ (M1), and CD69-MHC-I- (M2) thymocytes were compared between WT and Cd4cre A1fl/fl mice (lower panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were stained with antibodies against CD5 and analyzed by flow cytometry. Representative flow cytometric images for DP and 4SP thymocytes are shown (upper panel). The percentages of CD5- DP and 4SP thymocytes were compared between WT and Cd4cre A1fl/fl mice (lower panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-CD4, anti-CD8, anti-CD25 and anti-Foxp3 antibodies and were gated on 4SP thymocytes. Representative images are shown (upper panel). The percentages of CD25+Foxp3+ 4SP thymocytes (thymic Treg cells) were compared between WT and Cd4cre A1fl/fl mice (lower panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice were crossed with HY-TCR+ mice to generate Cd4cre A1fl/fl HY-TCR+ mice. Thymocytes isolated from male (A) and female (B) HY-TCR+ or Cd4cre A1fl/fl HY-TCR+ mice were stained with anti-CD4 and anti-CD8 antibodies and analyzed by flow cytometry. Representative images are shown (left panels). The absolute number of DP and 8SP thymocytes were compared between HY-TCR+ and Cd4cre A1fl/fl HY-TCR+ mice (right panels).",
    "ncbi_link": "Adar1: 56417
A1: 56417
Cd4: 12504
cre: 2777477
TCR: 21577///21473"
  },
  {
    "caption": "Thymocytes isolated from WT and Cd4cre A1fl/fl mice were labeled with Cell Proliferation Dye and then stimulated with plate-bound anti-CD3 and anti-CD28 antibodies for 4 days. Apoptotic (Annexin V+) and proliferating thymocytes (reduced intensity of Proliferation Dye) were determined by flow cytometry. Representative flow cytometric images are shown (left panel). The percentages of either Annexin V+ or Annexin V- proliferating thymocytes were compared between WT (n = 5) and Cd4cre A1fl/fl (n = 4) mice (right panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "The relative expression of anti-apoptotic genes in sorted 4SP thymocytes isolated from WT and Cd4cre A1fl/fl mice. Values represent the relative gene expression normalized to Actinβ mRNA and are displayed as the mean ± SEM (n = 3; Mann-Whitney U-test, *p < 0.05, N.S.; not significant). The mean value for the relative expression of each anti-apoptotic gene in WT 4SP thymocytes was set as one.",
    "ncbi_link": "Actinβ: 
A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Immunoblot analysis of total and phosphorylated ZAP70 and PLCγ1 expression in anti-CD3-stimulated thymocytes isolated from WT and Cd4cre A1fl/fl mice. The expression of GAPDH is shown as a reference. Representative images are shown (left panel). The band intensity of p-ZAP70 and p-PLCγ1 was normalized to that of total ZAP70 and PLCγ1, respectively",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Incidence of spontaneous colitis observed in wild-type (WT) and CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice (n = 11 for each group;",
    "ncbi_link": "Adar1: 56417
A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Representative images of HE staining of the colon dissected from a WT and Cd4cre A1fl/fl mouse. Scale bar, 200 μm.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Lymphocytes isolated from the colonic lamina propria of WT and Cd4cre A1fl/fl mice were stained with anti-IFNγ, anti-IL17 or anti-Foxp3 antibodies together with anti-CD4 antibodies and analyzed by flow cytometry. Representative images are shown (left panel). The absolute number of IFNγ-, IL17-, or Foxp3-expressing CD4+ T cells were compared between WT and Cd4cre A1fl/fl mice (right panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Splenocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-IFNγ and anti-IL17 together with anti-CD4 antibodies and were gated on CD4+ cells. Representative flow cytometry images are shown (upper panel). The percentages of IFNγ- and IL17-secreting CD4+ T cells were compared between WT and Cd4cre A1fl/fl mice (lower panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Splenocytes isolated from WT and Cd4cre A1fl/fl mice were stained with anti-Foxp3 together with anti-CD4 antibodies and were gated on CD4+ cells. Representative flow cytometry images are shown (upper panel). The percentages of Foxp3-expressing CD4+ T cells were compared between WT and Cd4cre A1fl/fl mice (lower panel).",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Effector T (Teff) cells isolated from the spleen of a WT mouse were stimulated with soluble anti-CD3 (5 μg/ml) in the presence of mitomycin C-treated splenocytes and were cultured with regulatory T (Treg) cells isolated from WT and Cd4cre A1fl/fl mice at the indicated ratios. After 72 h, the proliferative activity was measured. Values are displayed as the mean ± SEM (n = 3 for each group; Mann-Whitney U-test, N.S.; not significant). The mean value for the suppression of proliferative activity of Teff cells in a condition without Treg cells was set as 0%.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "RNA editing in the 3′UTR (C) and intronic region (D) of each gene indicated in the figures with their chromosomal location was validated by direct Sanger sequencing and the frequency of editing was compared among wild-type (WT) DP, WT 4SP thymocytes, and 4SP thymocytes isolated from CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice.",
    "ncbi_link": "Adar1: 56417
A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "The relative expression of each interferon-stimulated gene (ISG) indicated in the figure in sorted DP and 4SP thymocytes isolated from WT and Cd4cre A1fl/fl mice. Values represent the relative gene expression normalized to GAPDH mRNA and are displayed as the mean ± SEM (n = 3; Mann-Whitney U-test, *p < 0.05). The mean value for the relative expression of each ISG in WT DP thymocytes was set as one.",
    "ncbi_link": "GAPDH: 
A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "Immunoblot analysis of total and phosphorylated STAT1 expression in thymocytes isolated from WT and Cd4cre A1fl/fl mice (n = 2 for each group). The expression of GAPDH is shown as a reference.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477"
  },
  {
    "caption": "CD4+ cell-specific Adar1 knockout (Cd4cre A1fl/fl) mice were crossed with MDA5 knockout (Ifih1-/-) mice to generate Cd4cre A1fl/fl Ifih1-/- mice. Thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice were stained with anti-CD4, anti-CD8 and anti-TCRβ antibodies and analyzed by flow cytometry. Representative images are shown (left panel). The percentage of DN, DP, 4SP and 8SP thymocytes were compared among Ifih1-/- (n = 4), Cd4cre A1fl/fl Ifih1-/- (n = 5) and Cd4cre A1fl/fl (n = 7) mice (right panel). The same data shown in Fig 2C was used for Cd4cre A1fl/fl mice.",
    "ncbi_link": "A1: 56417
Adar1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586
MDA5: 71586"
  },
  {
    "caption": "The relative expression of each interferon-stimulated gene (ISG) indicated in the figure in sorted 4SP thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice. Values represent the relative gene expression normalized to GAPDH mRNA and are displayed as the mean ± SEM (n = 3; Mann-Whitney U-test, *p < 0.05). The mean value for the relative expression of each ISG in Ifih1-/- 4SP thymocytes was set as one.",
    "ncbi_link": "GAPDH: 
A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Immunoblot analysis of total and phosphorylated ZAP70 and PLCγ1 expression in anti-CD3-stimulated thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice. The expression of GAPDH is shown as a reference. Representative images are shown (left panel). The band intensity of p-ZAP70 and p-PLCγ1 was normalized to that of total ZAP70 and PLCγ1, respectively and displayed as the mean ± SEM (n = 3; Mann-Whitney U-test, N.S.; not significant) (right panel) by setting the mean value of stimulated Ifih1-/- samples at 60 sec as 1.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice were stimulated with plate-bound anti-CD3 (5 μg/ml) and anti-CD28 (1 μg/ml) antibodies for 72 h and the proliferative activity was measured. Values are displayed as the mean ± SEM (n = 3 for each group; Mann-Whitney U-test, *p < 0.05). The mean value for the activity of Ifih1-/- thymocytes in an unstimulated condition was set as one. For comparative analysis, the same data shown in Appendix Fig S1B was used for Cd4cre A1fl/fl mice.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice were stained with anti-CD4, anti-CD8, anti-CD69 and anti-MHC-I antibodies and were gated on 4SP thymocytes. Representative images are shown (upper panel). The percentages of CD69+MHC-I- (SM), CD69+MHC-I+ (M1), and CD69-MHC-I- (M2) thymocytes were compared among Ifih1-/- (n = 5), Cd4cre A1fl/fl Ifih1-/- (n = 3) and Cd4cre A1fl/fl (n = 3) mice (lower panel). The same data shown in Fig 2F was used for Cd4cre A1fl/fl mice.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Thymocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice were stained with anti-CD4, anti-CD8, anti-CD25 and anti-Foxp3 antibodies and were gated on 4SP thymocytes. Representative images are shown (upper panel). The percentages of CD25+Foxp3+ 4SP thymocytes (thymic Treg cells) were compared among Ifih1-/-, Cd4cre A1fl/fl Ifih1-/- and Cd4cre A1fl/fl mice (lower panel). The same data shown in Fig 2H was used for Cd4cre A1fl/fl mice.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Splenocytes isolated from Ifih1-/- and Cd4cre A1fl/fl Ifih1-/- mice were stained with anti-IFNγ and anti-IL17 together with anti-CD4 antibodies and were gated on CD4+ cells. Representative flow cytometry images are shown (left panel). The percentages of IFNγ- and IL17-secreting CD4+ T cells were compared among Ifih1-/- (n = 4), Cd4cre A1fl/fl Ifih1-/- (n = 5) and Cd4cre A1fl/fl mice (n = 6) (right panel). The same data shown in Fig 4E was used for Cd4cre A1fl/fl mice.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "No incidence of spontaneous colitis observed in Ifih1-/- (n = 5) and Cd4cre A1fl/fl Ifih1-/- (n = 11) mice. For side-by-side comparison with Cd4cre A1fl/fl mice",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "Representative images of HE staining of colon dissected from an Ifih1-/- and a Cd4cre A1fl/fl Ifih1-/- mouse. Scale bar, 200 μm.",
    "ncbi_link": "A1: 56417
Cd4: 12504
cre: 2777477
Ifih1: 71586"
  },
  {
    "caption": "(E) Wdr37+/+ and Wdr37−/− splenocytes were labeled with Indo-1, stained for cell surface markers to identify FOB cells, and stimulated with the indicated amounts of anti-IgM (black arrowhead). Normalized traces from three (2.5 mcg/ml anti-IgM) or four independent experiments (10 mcg/ml and 5 mcg/ml anti-IgM) are shown (Wdr37+/+ gray, Wdr37−/− pink). Mean Ca2+ flux for each genotype is overlaid in bold (Wdr37+/+ black, Wdr37−/− red).",
    "ncbi_link": "Wdr37: 207615"
  },
  {
    "caption": "(A) Immunoblot of ER mass, ER stress, and autophagy markers in Pacs1+/+ and Pacs1-/- splenic B cells that were left unstimulated or stimulated overnight with 5 mcg/ml IgM.",
    "ncbi_link": "Pacs1: 107975"
  },
  {
    "caption": "(B) Real-time quantitative PCR of IP3R and SERCA2 transcripts in B cells. Data are presented as mean ± SD from three independent Pacs1+/+ and Pacs1-/- pairs of mice.",
    "ncbi_link": "SERCA2: 11938
IP3R: 16438
Pacs1: 107975"
  },
  {
    "caption": "(D) Peak cytosolic Ca2+ concentration based on aequorin measurements as performed in (C). Symbols represent individual wells containing ~5 x 105 transfected 3T3 or Pacs1-/- cells from one experiment. Horizontal bars indicate mean. Two-tailed unpaired t test, **P < 0.01.",
    "ncbi_link": "Pacs1: 107975"
  },
  {
    "caption": "(E) Pacs1+/+ and Pacs1-/- NIH-3T3 cells (C1 and C2 from (A)) were transfected with ER-GCamP6-210. ER Ca2+ was measured before and after treatment with 10 µM ATP. Kinetic traces show the mean 488/405 nm excitation ratio of each cell line with error bars indicating SEM. N=30 cells (3T3), 16 cells (C1), 25 cells (C2). Data are representative of 2 independent experiments.",
    "ncbi_link": "Pacs1: 107975"
  },
  {
    "caption": "(B, C) Pacs1+/+ and Pacs1−/− mice were immunized with alum-ova and one week later with NP-Ficoll. Anti-ova IgG and anti-NP IgM titers were measured at 14 days and 7 days after immunization, respectively. Each symbol represents an individual mouse.",
    "ncbi_link": "Pacs1: 107975"
  },
  {
    "caption": "(H, I) Pacs1+/+ and Pacs1-/- mice were injected with EdU and the fraction of EdU+ FOB and MZB cells were measured in the spleen at 1, 4, and 7 days post-injection. Data are from one experiment.",
    "ncbi_link": "Pacs1: 107975"
  },
  {
    "caption": "(I) Enumeration of CD3+B220+ cells in the peripheral blood and lymph nodes of Faslpr/lpr dependent on Pacs1 expression. Horizontal bars indicate median value. Two-tailed Mann-Whitney test, **P < 0.01.",
    "ncbi_link": "Fas: 14103
Pacs1: 107975"
  },
  {
    "caption": "B-D Left ventricular LXRα expression in Wt and LXRα-Tg mice aged 12 weeks. (B) Western blot of LXRα in liver and LV tissue.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "B-D Left ventricular LXRα expression in Wt and LXRα-Tg mice aged 12 weeks. (B) Western blot of LXRα in liver and LV tissue. Quantification of (C) mRNA expression (normalized to 36b4; n = 6-8/group, *P < 0.00001 versus Wt) and (D) protein expression (normalized to GAPDH; n = 4/group, *P = 0.0001 versus Wt).",
    "ncbi_link": "36b4: 
LXRα: 22259"
  },
  {
    "caption": "H Relative mRNA levels of known LXRα-associated and target genes assessed with RT-PCR; n = 8/group. *P = 0.0003, #P = 0.0004, §P = 0.043, †P = 0.0009 versus Wt.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "LV/tibia ratios in sham- and TAC-operated Wt and LXRα-Tgmice; n = 21 Wt sham, n = 24 LXRα-Tg sham, n = 24 Wt TAC, n = 26 LXRα-TgTAC. *P < 0.00001 versus respective sham, #P = 0.00004.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "Quantification of cardiomyocyte cross-sectional area from WGA-FITC-stained histological sections; n = 5 Wt sham, n = 4 LXRα-Tg sham, n = 5 Wt TAC, n = 3 LXRα-TgTAC. **P = 0.00001 versus Wt sham, *P = 0.01 versus LXRα-Tg sham, #P = 0.01.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "Measurement of mRNA levels with RT-PCR to assess induction of fetal gene program, as well as hypertrophy (Rcan1) and fibrosis (Col1a1, Ctgf); n = 8 per group, except n = 7 in Wt TAC group. Myh6/Myh7: *P = 0.0001 versus Wt sham, #P = 0.00001; Anp: *P = 0.0005 versus LXRα-Tg sham, #P = 0.02; Bnp: *P = 0.0006 versus Wt sham, **P = 0.009 versus LXRα-Tg sham, #P = 0.03; Acta1: §P < 0.00001 versus Wt sham, *P = 0.01 versus LXRα-Tg sham, #P = 0.001; Rcan1: **P = 0.00004 versus Wt sham, *P = 0.05 versus LXRα-Tg sham, #P = 0.04; Col1a1: *P = 0.00003 versus Wt sham; Ctgf: §P < 0.00001 versus Wt sham, #P = 0.00001.",
    "ncbi_link": "Acta1: 11459
Col1a1: 12842
Ctgf: 14219
Myh6: 17888
Myh7: 140781
Anp: 230899
Bnp: 18158
LXRα: 22259
Rcan1: 54720"
  },
  {
    "caption": "A Echocardiographic assessment of percent fractional shortening in mice subjected to 5 weeks of TAC; n = 19 Wt sham, n = 22 LXRα-Tg sham, n = 24 Wt TAC, n = 26 LXRα-TgTAC. **P < 0.00001 versus Wt sham, *P = 0.0005 versus LXRα-Tg sham, #P = 0.009.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "B-D Hemodynamic measurements obtained in situ in sham- and TAC-operated mice; n = 6-8/group. (B) Mean arterial pressure (MAP) showed no significant differences. (C) LV end-systolic pressure (LVESP). **P < 0.00001 versus Wt sham, *P = 0.00004 versus LXRα-Tg sham, *P = 0.003. (D) LV end-diastolic pressure (LVEDP). *P = 0.02 versus Wt sham.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "B-D Hemodynamic measurements obtained in situ in sham- and TAC-operated mice; n = 6-8/group. (B) Mean arterial pressure (MAP) showed no significant differences. (C) LV end-systolic pressure (LVESP). **P < 0.00001 versus Wt sham, *P = 0.00004 versus LXRα-Tg sham, *P = 0.003. (D) LV end-diastolic pressure (LVEDP). *P = 0.02 versus Wt sham.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "Representative 18F-FDG images with microPET in the coronal and axial planes in Wt and LXRα-Tg mice 5 weeks post-TAC.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "Myocardial FDG uptake measured as standard uptake value (SUV); n = 4-6/group. *P = 0.04 versus Wt sham, **P = 0.02 versus LXRα-Tg sham, #P = 0.03, ##P = 0.01.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "GLUT protein expression in LV tissue normalized to GAPDH; n = 6/group. Glut1: *P = 0.01 versus LXRα-Tg sham, #P = 0.03; Glut4: *P = 0.03 versus LXRα-Tg sham, #P = 0.01.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "A LV/tibia ratios in sham- and TAC-operated WT and LXRα−/− mice; n = 10 WT sham, n = 8 LXRα−/− sham, n = 12 WT TAC, n = 10 LXRα−/− TAC. *P = 0.006 versus WT sham, **P = 0.00008 versus LXRα−/−sham.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "B, C Cardiac functional assessment at 5 weeks post-TAC. (B) Percent fractional shortening determined with echocardiography; n = 10 WT sham, n = 7 LXRα−/− sham, n = 12 WT TAC, n = 10 LXRα−/− TAC. *P < 0.00001 versus respective sham, §P = 0.06. (C) LV end-diastolic pressure (LVEDP) recorded in situ; n = 10 WT sham, n = 7 LXRα−/− sham, n = 10 WT TAC, n = 9 LXRα−/−TAC. *P = 0.001 versus WT sham, **P = 0.00005 versus LXRα−/− sham.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "D-G Relative mRNA gene expression as determined by RT-PCR, normalized to 36b4; n = 8/group. Anp: no significant differences; Bnp: *P = 0.01 versus WT sham, **P = 0.03 versus LXRα−/− sham; Myh6/Myh7: *P = 0.0002 versus WT sham, **P = 0.0003 versus LXRα−/− sham; Acta1: *P = 0.001 versus respective sham.",
    "ncbi_link": "36b4: 
Acta1: 11459
Myh6: 17888
Myh7: 140781
Anp: 230899
Bnp: 18158
LXRα: 22259"
  },
  {
    "caption": "D Western blot indicating Ad-LXRα- and PE-induced increases in global protein O-GlcNAcylation, which was abrogated following inhibition of HBP with DON. LXRα protein expression is shown, and GAPDH served as a loading control.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "E, F Modulation of Anp and Bnp mRNA levels by Ad-LXRα-induced O-GlcNAc signaling. Gene expression as determined by RT-PCR normalized to 36b4, n = 5 per condition in the absence of PE, n = 4 per condition in the presence of PE. *P = 0.02 versus Ad-cont, **P = 0.008 versus Ad-cont, #P = 0.03, ##P = 0.02.",
    "ncbi_link": "36b4: 
Anp: 230899
Bnp: 18158
LXRα: 22259"
  },
  {
    "caption": "C-F mRNA expression, normalized to 36b4, n = 6 per condition, except n = 5 for si-LXRα control. Anp: *P = 0.009 versus Ad-cont, #P = 0.004, ##P = 0.009; Bnp: *P = 0.004 versus Ad-cont, **P = 0.002 versus Ad-cont; Acta1: *P = 0.002 versus Ad-cont, §P = 0.06 versus Ad-cont, #P = 0.02; Rcan1: *P = 0.03 versus Ad-cont, **P = 0.004 versus Ad-cont, #P = 0.004.",
    "ncbi_link": "36b4: 
Acta1: 11459
Anp: 230899
Bnp: 18158
LXRα: 22259
Rcan1: 54720"
  },
  {
    "caption": "A, B Western blot analyses of global protein O-GlcNAc levels in left ventricles of mice with either (A) cardiac-specific LXRα overexpression or (B) LXRα deficiency and subjected to 5 weeks TAC.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "C, D Nuclear protein extracts were precipitated with agarose WGA in the absence or presence of GlcNAc, a competitor, and analyzed by Western blot with antibodies against Mef2c, GATA4, or Nkx-2.5, known transcription factors of natriuretic peptides; bands represent 3 pooled hearts per Wt and LXRα-Tg lanes, and (D) quantification is for n = 2, expressed as fold change.",
    "ncbi_link": "LXRα: 22259"
  },
  {
    "caption": "A-H Effect of CCCP on the localisation of Noc and NocNΔ10. Cellular localisation of Noc‐mYFP (DWA206) and NocNΔ10‐mYFP (DWA382) either with no additions (NA) or after CCCP treatment (5 min; 100 μM), as indicated. Scale bar, 2.5 μm.",
    "ncbi_link": "Noc: 937920"
  },
  {
    "caption": "I-L Effect of Noc overproduction on cell division. Exponentially growing cultures of DWA119 (Δnoc, Pspac(hy)‐noc) and DWA282 (Δnoc, Pspac(hy)‐nocNΔ10) were examined after growth for 1 h with 1 mM IPTG. Cell membranes and DNA were stained with FM5‐95 and DAPI, respectively. Insets show corresponding phase contrast light microscopy images. Scale bar, 5 μm.",
    "ncbi_link": "spac: 11242127
Noc: 937920
noc: 937920"
  },
  {
    "caption": "M Complementation of noc in a Δnoc ΔminCD background. Strains DWA564 (Δnoc, ΔminCD, Pxyl‐noc‐myfp) and 566 (Δnoc, ΔminCD, Pxyl‐nocNΔ10‐myfp) were streaked on nutrient agar (NA) plates in the presence of 0.5% w/v xylose and incubated at 30 and 39°C, as indicated.",
    "ncbi_link": "noc: 937920"
  },
  {
    "caption": "N Effect of Noc and NocNΔ10 overproduction on sporulation. Strains DWA119 (Δnoc, Pspac(hy)‐noc) and DWA282 (Δnoc, Pspac(hy)‐nocNΔ10) were streaked on NA plates in the absence and presence of 1 mM IPTG, as indicated, and photographed after 48 h at 37°C.",
    "ncbi_link": "spac: 11242127
Noc: 937920
noc: 937920"
  },
  {
    "caption": "O Western blot analysis of cellular fractions (T, total; C, cytosolic; M, membrane) of strains DWA119 and 282 expressing Noc or NocNΔ10, respectively. Proteins were detected using polyclonal antibodies against Noc, DnaA and PBP2B. Antibodies were used at a dilution of 1:10,000.",
    "ncbi_link": "Noc: 937920"
  },
  {
    "caption": "B Growth of strains DWA350 (Δnoc ΔminCD) and DWA307 (Δnoc ΔminCD, Pxyl‐HCVAH‐NocNΔ10) on nutrient agar plates at 30 and 48°C in the absence and presence of 0.5% w/v xylose, as indicated.",
    "ncbi_link": "Noc: 937920
noc: 937920"
  },
  {
    "caption": "G, H Cellular localisation of HCVAH‐NocNΔ10‐YFP (G) in strain DWA193 (Δnoc, Pxyl‐HCVAH‐nocNΔ10‐yfp) and overlay showing DAPI‐stained DNA (H). The strain was grown at 30°C in CH medium. Inset shows the corresponding phase contrast light microscopy image. Scale bar, 5 μm.",
    "ncbi_link": "Noc: 937920
noc: 937920"
  },
  {
    "caption": "A-F Localisation of ParB‐box mutants. Cellular localisation of (A) Noc‐mYFP (DWA206), (B) NocQ68R‐mYFP (DWA285), (C) NocG86S‐mYFP (DWA286), (D) NocR88A‐mYFP (DWA545), (E) NocR89A‐mYFP (DWA546) and (F) NocR91A‐mYFP (DWA547). Insets show the corresponding phase contrast images. Scale bar, 5 μm.",
    "ncbi_link": "Noc: 937920"
  },
  {
    "caption": "G Ability of ParB‐box mutants to rescue the growth defect of Δnoc ΔminCD. Strains DWA564 (Pxyl‐noc‐myfp), 590 (Pxyl‐nocQ68R‐myfp), 568 (Pxyl‐nocG86S‐myfp), 598 (Pxyl‐nocR88A‐myfp), 600 (Pxyl‐nocR89A‐myfp) and 602 (Pxyl‐nocR91A‐myfp) were streaked on plates containing 0.5% w/v xylose and incubated for 18 h at either 30 or 39°C, as indicated, before being photographed.",
    "ncbi_link": "noc: 937920"
  },
  {
    "caption": "H-O ParB‐box mutants are dominant‐negative. Cells of strains DWA362 (ΔminCD, Pspac(hy)‐noc), 363 (ΔminCD, Pspac(hy)‐nocNΔ10), 364 (ΔminCD, Pspac(hy)‐nocQ68R) and 365 (ΔminCD, Pspac(hy)‐nocG86S) were examined after growth for 2 h at 42°C with either no additions (NA) (H-K) or in the presence of 1 mM IPTG (L-O), as indicated. Cell membranes were stained with FM5‐95. Insets show the corresponding phase contrast images. Scale bar, 5 μm.",
    "ncbi_link": "spac: 11242127
noc: 937920"
  },
  {
    "caption": "A-C Representative images of TetR‐mCherry in cells lacking (A) or containing (B and C) the NBS plasmid pDWA117. Strains DWA427 (A) and 429 (B and C) (both strains contain Pspac‐noc) were examined after growth for 2 h in the absence (A and B) and presence (C) of 1 mM IPTG. DNA was stained with DAPI.",
    "ncbi_link": "DWA117: 
spac: 11242127
noc: 937920"
  },
  {
    "caption": "D-G Representative images showing the localisation of (D) Noc‐mYFP (DWA519), (E) NocNΔ10‐mYFP (DWA522), (F) NocQ68R‐mYFP (DWA520) and (G) NocG86S‐mYFP (DWA521), in the presence of the NBS plasmid pSG4929.",
    "ncbi_link": "SG4929: 
Noc: 937920"
  },
  {
    "caption": "A, B Effects of Noc overproduction on cell division and nucleoid morphology in E. coli. Cells of strain DWA261 carrying pDWA37 (PA1/04/03‐noc) were examined after growth in LB with either no additions (A) or after induction for 1 h with 1 mM IPTG (B).",
    "ncbi_link": "noc: 937920
Noc: 937920"
  },
  {
    "caption": "C-E Effects of overproduction of Noc variants on nucleoid morphology. Cells of strains DWA266 (PA1/04/03‐nocNΔ10) (C), 270 (PA1/04/03‐HCVAH‐nocNΔ10) (D) and 267 (PA1/04/03‐nocCΔ50) (E) carrying plasmids for the overproduction of the indicated mutants (see cartoons underneath panels) were grown in LB and examined after growth for 1 h in the presence of 1 mM IPTG. Cell membranes and DNA were stained with FM5‐95 and DAPI, respectively. Scale bar, 5 μm.",
    "ncbi_link": "noc: 937920"
  },
  {
    "caption": "A, B Effects of Spo0J and Noc30‐Spo0J overproduction on cell division and nucleoid morphology in E. coli. Cells of strains DWA271 (PA1/04/03‐spo0J) (A) and 272 (PA1/04/03‐noc‐spo0J) (B) were grown in LB in the presence of 1 mM IPTG, to induce the expression of either Spo0J (A) or the Noc‐Spo0J hybrid (B), and were examined 1 h post‐induction. Cell membranes and DNA were stained with FM5-95 and DAPI, respectively. Scale bar, 5 μm.",
    "ncbi_link": "noc: 937920
Noc: 937920
spo0J: 937907
Spo0J: 937907"
  },
  {
    "caption": "B sgRNA frequencies (log2 of fold change) in PD-L1low cells unstimulated (left) or IFN-γ stimulated (right). Enriched sgRNAs (dashed line) are highlighted; hit genes (black, red) and controls (green, yellow or purple) are shown and labeled with target gene names.",
    "ncbi_link": "PD-L1: 29126"
  },
  {
    "caption": "C sgRNA frequencies (log2 of fold change) in viability screen. sgRNAs targeting controls are highlighted; essential (orange), non-essential (blue). Genes attributed to PD-L1 modulation are shown in different colors (red, yellow and purple).",
    "ncbi_link": "PD-L1: 29126"
  },
  {
    "caption": "A PD-L1 cell surface presentation (percentage ± SD) in RKO mock control (black) or monoclonal MLLT6 knockout cells (grey) (Student's t-test; **p < 0.01; n=3 biological replicates; degrees of freedom (df)=2).",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": " B MLLT6 BAC mediated rescue in U2OS cells (left) showing percentage ± SD of PD-L1 cell surface presentation in mock control (black), MLLT6 polyclonal knockout (light grey) and MLLT6 knockout + BAC cells (dark grey) (Student's t-test; *p < 0.05; n=3 biological replicates; df=2). Representative flow cytometry plots (right) of PD-L1 cell surface presentation after staining with anti-PD-L1 antibody (top right, bottom left, bottom right) and isotype control (top left). Percentages of cells in the PD-L1+ gate as indicated. ",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": " C Total cellular protein levels of PD-L1 (top) and GAPDH (bottom) in monoclonal RKO MLLT6 knockout, mock control or MLLT6 knockout + BAC cells visualized by immunoblotting. Numbers indicate relative band intensities of PD-L1 protein normalized to GAPDH. ",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": " D PD-L1 transcript levels in U2OS mock (black) and polyclonal MLLT6 knockout lines (grey) treated with and without IFN-γ normalized to expression in mock U2OS cells without IFN-γ treatment (ANOVA; **p < 0.01; n=4 biological replicates; df=12). ",
    "ncbi_link": "PD-L1: 29126
MLLT6: 4302"
  },
  {
    "caption": " E Representative flow cytometry plots of PD-L1 cell surface presentation in the presence and absence of IFN-γ in mock, polyclonal MLLT6 knockout and PD-L1 knockout cells. Percentages of cells in the PD-L1+ gate after staining with anti-PD-L1 antibody or isotype control as indicated. ",
    "ncbi_link": "PD-L1: 29126
MLLT6: 4302"
  },
  {
    "caption": " F Total cellular protein levels of PD-L1 (top) and GAPDH (bottom) in U2OS polyclonal MLLT6 knockout or mock control cells with and without IFN-γ stimulation. Numbers indicate relative band intensities of PD-L1 protein normalized to GAPDH. ",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": " B Relative cell numbers (± SD; n=3; biological replicates) of U2OS mock (black) or polyclonal MLLT6 knockout (grey) cells treated with varying amounts of EpCAM-CD3 BiTE and CTLs (Student's t-test; **p < 0.01; degrees of freedom (df)=4). ",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": " C Kaplan Meier survival plot (left) showing changes in survival (percent) of mock (grey) and MLLT6 knockout (red) cells treated with CTLs and EpCAM-CD3 BiTE over a course of 9.5 hours. Representative images (right) of time-lapse fluorescence microscopy following U2OS mock (eGFP tagged, green) and MLLT6 knockout (mCherry tagged, red) cells immediately (top left and bottom left) after adding CTLs and EpCAM-CD3 BiTE and 9.5 hours later (top right and bottom right) (scale bars = 100 μm). ",
    "ncbi_link": "eGFP: 
mCherry: 
MLLT6: 4302"
  },
  {
    "caption": " D Relative cell numbers (left) (± SD; n=3; biological replicates) of mock (black), PD-L1 (dark grey) or MLLT6 (light grey) knockout cells treated with BiTE or bi-specific antibodies and CTLs as indicated (Student's t-test; **p < 0.01; df=4). Representative images (right) from bright field microscopy of polyclonal U2OS mock (top), PD-L1 (middle) or MLLT6 (bottom) knockout cells treated without or with EpCAM-CD3 BiTE or bispecific antibodies. ",
    "ncbi_link": "PD-L1: 29126
MLLT6: 4302"
  },
  {
    "caption": " E Relative normalized cell numbers (± SD; n=3; biological replicates) of U2OS mock (left), MLLT6 (middle) or PD-L1 (right) knockout cells treated with EpCAM-CD3 BiTE and CTLs in the presence (grey) or absence (black) of IFN-γ (Student's t-test; **p < 0.01; df=4 ). ",
    "ncbi_link": "PD-L1: 29126
MLLT6: 4302"
  },
  {
    "caption": "A Scatter plots of pairwise comparisons of transcript expression in U2OS cells. Plots describe log2 fold change in transcript expression in mock and polyclonal MLLT6 knockout cells treated with and without IFN-γ as indicated. Horizontal axis shows log2 fold change in transcript expression and vertical axis represents statistical significance (log10 of p-value, n=3) with candidates nominated for further validation (red).",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": "B Correlation plots describing log2 fold change of transcripts in RNA sequencing (x axis) and Nanostring (y axis) measurements in mock cells +/- IFN-γ (left) and MLLT6 knockout cells with IFN-γ (right). Transcripts previously described to have a role in tumor immunity (red) and PD-L1 (blue) are represented on the plots as indicated.",
    "ncbi_link": "PD-L1: 29126
MLLT6: 4302"
  },
  {
    "caption": "C Changes (log2 fold) in transcript expression (left) of select immune-related genes in U2OS mock or MLLT6 knockout cells treated with or without IFN-γ and total protein levels measured by immunoblotting (right). Numbers indicate band intensities normalized to GAPDH.",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": "A Immunoblot expression analysis of proteins implicated in IFNγ signal transduction in U2OS mock or polyclonal MLLT6 knockout cells treated with or without IFN-γ. Numbers indicate band intensities normalized to GAPDH.",
    "ncbi_link": "MLLT6: 4302"
  },
  {
    "caption": "B Immunoblot showing total protein levels of STAT1 isoforms (α and β), IDO1, GBP5 and CD74 in wild type U2OS cells transfected with esiRNAs targeting renilla luciferase (Rluc, negative control), total STAT1, STAT1α and STAT1β treated with and without IFN-γ.",
    "ncbi_link": "renilla luciferase: 
Rluc: 
STAT1: 6772
STAT1α: 6772
STAT1β: 6772"
  },
  {
    "caption": "A Number of target genes identified using differential expression for each assayed TF. *genes identified as essential for self-renewal of Hoxb8-FL cells either in (Basilico et al, 2020).",
    "ncbi_link": "Hoxb8: 15416"
  },
  {
    "caption": "D Changes in expression for genes co-regulated by separate Cebpa/Meis1/Spi1 and Hoxb8 perturbations (FDR <0.1 and |log2(FoldChange)| > 0.2). The interaction row indicates changes beyond simple additive effect (white = additive effect). Each gene was annotated with an interaction class (int. class) as explained in (C), using the |log2(FoldChange)| > 0.2) threshold to assign change direction. E Fractions of genes in each interaction class showed in (D). ",
    "ncbi_link": "Cebpa: 12606
Hoxb8: 15416
Meis1: 17268
Spi1: 20375"
  },
  {
    "caption": "C, D Genomic views of relevant TF binding to Cebpa and Gata3 loci (supporting direct regulatory interactions identified in Figs 3A,B,C). The red arrow indicates a putative enhancer element, which is bound by Ebf1 and flanked by AcK27-rich regions.",
    "ncbi_link": "Cebpa: 12606
Gata3: 14462"
  },
  {
    "caption": "C Correlation in gene expression changes following Ebf1 and Gata3 loss in Hoxb8-FL cells. Each quadrant corresponds to a set of target genes with a common regulation by Gata3/Ebf1 - I - inhibition/inhibition, II - activation/inhibition, III - activation/activation, IV - inhibition/activation. For each group the sums of scaled expression values in mouse LK/LSK or human BMMC landscapes is plotted to highlight cell types with the highest overall expression. For landscape annotation see Fig 7B andE.. Changes in expression for example genes are provided in Appendix Fig 2G-J. Blue line indicates the linear fit with shaded areas as confidence intervals.",
    "ncbi_link": "Ebf1: 13591
Ebf1: 1879
Gata3: 14462
Gata3: 2625"
  },
  {
    "caption": "E Correlation in expression changes after 24h following Ebf1 loss in Hoxb8-FL cells and re-expression of Ebf1 in Ebf1-/- pre-pro B cells (Li et al, 2018). Blue line indicates the linear fit with shaded areas as confidence intervals.",
    "ncbi_link": "Ebf1: 1879
Ebf1: 13591"
  },
  {
    "caption": "F, G Expression of the key marker genes (F) and Ebf1, Pax5, Gata3, Cebpa factors (G) along pseudotime corresponding to the B-cell differentiation trajectory in human foetal liver cells, data from (Popescu et al, 2019).",
    "ncbi_link": "Cebpa: 1050
Ebf1: 1879
Gata3: 2625
Pax5: 5079"
  },
  {
    "caption": "A . MC3T3E1 cells were transfected with pTOPFLASH together with pCMV-β-gal. After 24 h, the cells were treated with DMSO, KY-02061 in DMSO, or 5 µM PolyR-DBM for 2 days. The luciferase activities of whole cell lysates were measured and normalized with β-galactosidase activities. [n=3]",
    "ncbi_link": "TOPFLASH: 
β-gal: 
β-galactosidase: "
  },
  {
    "caption": "A . MC3T3E1 cells were transfected with pTOPFLASH together with pCMV-β-gal. After 24 h, the cells were treated with indicated dose of KY-02327 for 2 days. The luciferase activities of whole cell lysates were measured and normalized with β-galactosidase activities. [n=3]",
    "ncbi_link": "TOPFLASH: 
β-gal: 
β-galactosidase: "
  },
  {
    "caption": "D. MC3T3E1 cells were treated with indicated concentrations of KY-02327 for 14 days. The mRNA level of collagen 1a (Col1a) was measured by quantitative real-time qRT-PCR. [n=3]",
    "ncbi_link": "Col1a: 12842
collagen 1a: 12842"
  },
  {
    "caption": "E. MC3T3E1 cells were treated with indicated concentrations of KY-02327 for 21 days. The mRNA level of osteocalcin (OCN) was measured by qRT-PCR. [n=3]",
    "ncbi_link": "OCN: 12096
osteocalcin: 12096"
  },
  {
    "caption": "(C) Adult phenotypes of the ash1 and NSD mutants. In ash122/ash121 mutants (designated as ash1-) the loss of Abd-B expression results in partial transformation of abdominal segments 6 and 5 toward segments 5 and 4, which is visible from the partial loss of pigmentation on tergites 5 and 6 (t5 and t6) and appearance of bristles on sternite 6 (s6, marked with black arrows). The loss of Ubx expression causes transformation of the third thoracic to the second thoracic segment visible as partial haltere (H) to wing and third leg (3L) to second leg (2L) transformations. The former is evident from the change in the haltere shape and the appearance of multiple bristles (black arrowheads). The latter is indicated by the apical and pre-apical bristles (red arrows) on the tibia of the third leg of ash1 mutants. These are normally present on 2L but absent on 3L (compare to wild-type). Also note the appearance of additional hypopleural bristles on the third thoracic segment of the ash1- flies (red arrowheads), which indicate its transformation towards the second thoracic segment. Phenotype of the NSDds46/NSDds46 (NSD-) flies is indistinguishable from wild-type and the phenotype of the double ash122,NSDds46/ ash122,NSDds46 (ash1-,NSD-) flies is no more severe than that of the single ash122/ash121 (ash1-) mutants.",
    "ncbi_link": "Abd-B: 47763
ash1: 40133
NSD: 43351
Ubx: 42034"
  },
  {
    "caption": "(D) Ubx expression in the haltere imaginal discs. The expression was assayed by immunostaining with antibodies against Ubx (red) and acetylated H3K18 (green, positive control). While ash122/ash121 (ash1-) larvae show stochastic clonal loss of the Ubx immunostaining in haltere discs (yellow dashed lines), Set2- larvae have uniform expression of Ubx throughout the haltere disc, resembling that in the wild-type larvae. Scale bars indicate 100μm.",
    "ncbi_link": "ash1: 40133
Set2: 32301"
  },
  {
    "caption": "(A) Adult phenotypes of the ash122/ash19011 flies supplemented with transgenic constructs expressing either the full-length Ash1 (Ash1FL) or the truncated variants lacking the PHD (Ash1∆PHD) or the SET (Ash1∆SET) domains. Note the third leg (L3) to second leg (L2), haltere (H) to wing (black arrows), t5 to t4 and t6 to t5 transformations in the Ash1∆PHD and the Ash1∆SET but not in the Ash1FL flies. The latter are evident from the partial loss of pigmentation in t6 and t5, or the appearance of small bristles (trichomas) on t6 of the Ash1∆PHD and the Ash1∆SET flies in the area that is normally naked (Ash1FL, yellow dashed line).",
    "ncbi_link": "ash1: 40133
Ash1: 40133"
  },
  {
    "caption": "(B) Two-fold dilutions of total nuclear protein extracts from the third instar larvae of the ash122/ash19011 mutants supplemented with various transgenic constructs and wild type flies were analyzed by western blot with anti-Ash1 antibodies. Arrowhead indicates the position of Ash1 protein. Note that transgenic proteins are expressed at comparable level.",
    "ncbi_link": "ash1: 40133"
  },
  {
    "caption": "Two-fold serial dilutions of the total protein extracts from the wild-type, ash122/ash19011 (ash1-), ash122,NSDds46/ash19011,NSDds46 (ash1-, NSD-) and Set21 (Set2-) larval brains, imaginal discs and salivary glands were analyzed by western blot with antibodies against H3K36me1 (A), H3K36me2 (B) and H3K36me3 (C). Note the strong (>10-fold) reduction of H3K36me3 signal in the Set2- extract and the slight (~2-fold) reduction of H3K36me1 signal in the ash1- and ash1-, NSD- extracts. The protein extracts from the wild-type, double ash1-, NSD- and single NSD- and Set2- mutants (right panels) were analyzed together on the same membrane, however the images of the H3K36me1 and H3K36me3 western blots were modified to splice out the marker lane between the ash1-,NSD- and the Set2- extracts. Western blots with constitutively expressed BEAF-32 protein were used as loading controls.",
    "ncbi_link": "ash1: 40133
NSD: 43351
Set2: 32301"
  },
  {
    "caption": "Chromatin from the wild-type (dark blue bars), ash122/ash19011 (ash1-, red bars) and transgenic ash122/ash19011 (Ash1FL, light blue bars; Ash1∆PHD, green bars; Ash1∆SET, orange bars) larvae was subjected to immunoprecipitation with the antibodies against H3K36me1 , H3K36me2 Histograms show the mean of the two independent experiments (n=2) with dots indicating individual experimental results. An intergenic region on chromosome 3R (intergenic) and the constitutively active TBP-associated factor 4 (Taf4) gene serve as controls. The loss of Ash1 ChIP signal in the ash1- larvae indicates that the selected genes are the genuine Ash1 binding sites.",
    "ncbi_link": "ash1: 40133
Ash1: 40133
Taf4: 39765
TBP-associated factor 4: 39765"
  },
  {
    "caption": "Chromatin from the wild-type (dark blue bars), ash122/ash19011 (ash1-, red bars) and transgenic ash122/ash19011 (Ash1FL, light blue bars; Ash1∆PHD, green bars; Ash1∆SET, orange bars) larvae was subjected to immunoprecipitation with the antibodies against Ash1 (C). Histograms show the mean of the two independent experiments (n=2) with dots indicating individual experimental results. An intergenic region on chromosome 3R (intergenic) and the constitutively active TBP-associated factor 4 (Taf4) gene serve as controls. The loss of Ash1 ChIP signal in the ash1- larvae indicates that the selected genes are the genuine Ash1 binding sites.",
    "ncbi_link": "ash1: 40133
Ash1: 40133
Taf4: 39765
TBP-associated factor 4: 39765"
  },
  {
    "caption": "(B) The ∆HisC; 12xH3K36R and control ∆HisC; 12xWT flies show no homeotic transformations and are indistinguishable from the wild-type.",
    "ncbi_link": "HisC: 
H3: 3772518///3772489///3772231///318847///3772374///3772191///3772173///3772163///3772149///3772032///3771959///3771792///3772607///3772619///3772517///3772552///3772370///3772421///3772189///3771723///3771771///3771729///3772198///31848///33736"
  },
  {
    "caption": "(A) The Abd-B expression in the Central Nervous System (CNS) of stage 16 embryos was assayed by immunostaining with antibodies against Abd-B (red). In the ash122/TM3, Sb, e Kr::GFP or ash19011/TM3, Sb, e Kr::GFP embryos (heterozygous control), Abd-B is expressed in parasegments 14 to 10 in a gradient that recedes from the posterior to anterior parasegment. In the ash122/ash19011 mutants the Abd-B gradient is much steeper, with reduced staining of parasegments 13 and 12 and at the edge of the detection in parasegments 11-10. Heterozygous control and ash122/ash19011 mutant embryos were stained together and separated by strong GFP expression (green) in the Bolwig's organs (white arrows). Here and in B the embryos are oriented with anterior pole facing the top and scaling bars correspond to 50μm.",
    "ncbi_link": "ash1: 40133"
  },
  {
    "caption": "(B) Unlike ash1 mutants, embryos homozygous for His3.3A, His3.3B, ∆HisC deletions and supplemented with 12xH3K36R transgene (His3.2-,His3.3-,H3K36R) display the wild-type Abd-B immunostaining pattern (red), the same as the control embryos heterozygous for His3.3A, and ∆HisC deletions. In this experiment, immunostaining with antibodies against acetylated H3K18 (green) served as positive control.",
    "ncbi_link": "His3.2: 
His3.3: 
HisC: 
ash1: 40133
His3.3A: 33736
His3.3B: 31848
H3: 3772518///3772489///3772231///318847///3772191///3772374///3772173///3772163///3772149///3772032///3771959///3771792///3772607///3772619///3772517///3772552///3772370///3772421///3772189///3771723///3771771///3771729///3772198///31848///33736"
  },
  {
    "caption": "(D) Reverse transcription and quantitative PCR (RT-qPCR) measurement of Abd-B expression in His3.2-,His3.3-,H3K36R embryos. Expression of Abd-B in stage 16 embryos, which are homozygous for His3.3A, His3.3B, and ∆HisC deletions and carry 12xH3K36R transgene (mutant), is not reduced compared to their wild-type counterparts (control 1) or embryos heterozygous for His3.3A, and ∆HisC deletions (control 2). Histograms show the mean of the two independent experiments (n=2) with dots indicating individual experimental results.",
    "ncbi_link": "His3.2: 
His3.3: 
HisC: 
Abd-B: 47763
His3.3A: 33736
His3.3B: 31848"
  },
  {
    "caption": "HEK293T cells were transfected for 48 hours with each mitoTev-TALE (11.5 and 8.5 RVDs) and total cell extracts were used for western-blots with anti-T2A antibody. Molecular weights of the two different mitoTev-TALEs are ~85KD and ~70KDa, respectively",
    "ncbi_link": "Tev: 1258722
TALE: 34179212"
  },
  {
    "caption": "MtDNA heteroplasmy analyzed by PCR/RFLP, 24 hours post mitoTev-TALE and mitoTALEN transfection. The RFLP analysis shows increased %WT mtDNA in sorted cells when compared to the the untransfected. mitoTALEN monomers positive for both eGFP and mCherry were isolated as "Yellow". The "Black" cells represent the mitoTALEN sorted population of cells negative for eGFP and mCherry and the "GFP-+" population represents mitoTev-TALE sorted cells with low levels of eGFP fluorescence. GFP++ were cells positive for GFP after mitoTev-TALEs transfections",
    "ncbi_link": "eGFP: 
GFP: 
mCherry: 
TALEN: 
Tev: 1258722
TALE: 34179212
TALEs: 34179212"
  },
  {
    "caption": "Determination of the levels of mtDNA (ND1/ACTB) by qPCR of mutant cybrids transfected with MERRF mitoTev-TALE",
    "ncbi_link": "ACTB: 60
Tev: 1258722
ND1: 4535
TALE: 34179212"
  },
  {
    "caption": "mtDNA levels in wild-type sorted cells transfected with the MERRF mitoTev-TALE. Data is expressed as percentage of the Untransfected cells (%UNT)",
    "ncbi_link": "Tev: 1258722
TALE: 34179212"
  },
  {
    "caption": "RFLP analyses of high mutant cybrids transfected with the MERRF mitoTev-TALE. The sorted cells were analyzed at different times of growth by PCR/RFLP as previously described",
    "ncbi_link": "Tev: 1258722
TALE: 34179212"
  },
  {
    "caption": "Flow cytometry diagram of gated sorted cells. The GFP-+ represent the cells with low levels of fluorescence, GFP++ showed intermediate levels of fluorescence while GFP+++ had the highest levels",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Oxygen consumption rate (OCR) upon sequential injection of oligomycin (Oligo), FCCP and rotenone (Rot) + antimycin (AA), in untransfected, sorted "GFP-+" and "GFP++". The error bars represent the mean±SEM of 5-7 separate experiments",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Quantification of 4-6 independent experiments comparing the basal respiration, maximal respiration, spare respiratory capacity and ATP-linked respiration of the UNT versus "GFP-+", "GFP++" and WT cells. The cells were analyzed between 25-28 days after sorting",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A-J: Igsf10 expression was not observed at E10.5 (A, sagittal section) but readily detectable at E12.5, in the NM (B and C, frontal sections) and E14.5, along the migratory path of GnRH neurons (D, frontal section). Igsf10 positive cells were negative for Isolectin b4 (marker of vasculature) at all developmental stages (E, at E14.5). Incubation with the sense probe resulted in no signal at all stages (E14.5 shown in F). Peripherin-positive cells olfactory axons were extending within the Igsf10-positive NM (G and H). Cxcl12 mRNA expression is shown in I (E14.5, frontal section). GnRH neurons are located in the MPOA by E17.5 (J, frontal section) in an Igsf10 negative area.",
    "ncbi_link": "Cxcl12: 20315
Igsf10: 242050"
  },
  {
    "caption": "K-N: In human 11pcw brains, IGSF10 expression pattern was similar to that observed in mouse, with GnRH neurons interspersed in an IGSF10-positive NM (K-N, frontal sections, see also schematic in P). IGSF10 positive cells were also detected in the olfactory bulb (OB, panel O). Sense probe resulted in no specific signal (panel N).",
    "ncbi_link": "IGSF10: 285313"
  },
  {
    "caption": "A: Levels of Igsf10 expression in native NIH3T3 cells, and cells stably expressing a scrambled (sh-scr) or Igsf10 (sh-Igsf10) shRNA.",
    "ncbi_link": "Igsf10: 242050"
  },
  {
    "caption": "B and C: migration of GN11 cells from aggregates into NIH3T3 sh-scr (B) or sh-Igsf10 (C).D: Analysis of the migration index (see Methods).",
    "ncbi_link": "Igsf10: 242050"
  },
  {
    "caption": "E: RT-PCR analysis in zebrafish of total embryos and larvae showing the expression of Igsf10 mRNA at different time points. Expected band size: 905 bp.",
    "ncbi_link": "Igsf10: 100329456"
  },
  {
    "caption": "F: Representative time-lapse analysis of mispair control (Control Sp-MO and Control ATG-MO) and Igsf10 morpholinos (Igsf10 Sp-MO and Igsf10 ATG-MO) injected Tg(gnrh3:EGFP) embryos and larvae, at different time-points. Images show lateral view of live larvaehead (48 and 72 hpf) and dorsal view (4 and 5 dpf) of live larvaehead; anterior is left. White arrowheads indicate normal GnRH3 neuron clusters in the olfactory area of control embryos. Brackets show the extension of the projections towards the hypothalamus. White arrows indicate examples of abnormal GnRH3 neurons scattered in the olfactory area of morphants accompanied by lack of projections toward the hypothalamus, indicated with Δ (hpf - hours post fertilisation; dpf - days post fertilisation.) Scale bar, 100 um (panels at 48 and 72hpf in F), 150 um (panels at 4 and 5dpf in F). Panel G: Effect of Igsf10 Splice-site morpholino injection observed at 48hrs. Quantification of the percentage of embryos showing an abnormal GnRH3-neuron phenotype was significantly higher in Igsf10 Splice-site-MO (Sp-MO) injected embryos compared to relative controls. *: p=0.02422, **: p=0.00101, ***: p=0.00020, ****: p=0.00001.",
    "ncbi_link": "Igsf10: 100329456"
  },
  {
    "caption": "ApoE-/- common carotid arteries (CCA) were dissected into plaque and adjacent non-plaque areas, then RNA isolated. (A) Graphed qPCR quantification of collagen 1A1 (left panel) and collagen 3A1 (right panel) mRNA expression in plaque (P) and non-plaque (NP) areas of ApoE-/- carotid arteries. Three assays were carried out, and the data represent mRNA expression normalized to NP, and the mean + SEM, n=4, 3, 4 of mice/group. * represents p<0.001 compared with LNA-miR-29 non-plaque region.",
    "ncbi_link": "ApoE: 11816
collagen 1A1: 12842
collagen 3A1: 12825
miR-29: 387224///723963///387223///387222"
  },
  {
    "caption": "Proteome studies analyze the frequency distribution of protein changes after the transfection of primary murine aortic VSMCs with pre-miR-29b, anti-miR-29b, pre-miR-30c, or anti-miR-30c. A log2 fold change of −1 or 1 was used as cutoff. Log2 (fold change) is calculated using the normalized spectral counts and averaged for the 3 biological replicates. (A) The log (fold change) for differentially secreted proteins following overexpression or inhibition of pre-miR-29b was analyzed, and significantly changed miR-29 confirmed target transcripts are shown. FDR indicates false discovery rate. The complete list of significant proteins is in (Appendix Table S1A-B).",
    "ncbi_link": "miR-29b: 723963///387223
miR-29: 387224///723963///387223///387222
miR-30c: 723964///387227"
  },
  {
    "caption": "(B) Thirty microliters of conditioned medium from VSMCs transfected with pre-miR-29b and anti-miR-29b were separated by SDS-PAGE before validation of COL3A1 by immunoblotting. (C) Densitometry analysis of COL3A1 signal from blot in (B) (pre-miR, left *p<0.001, anti-miR, right *p=0.002) . All data in (C) represent the mean + SEM, *p<0.05 versus other groups in anti- and pre- groups. Level of significance was determined using one-way ANOVA with Bonferroni's post test.",
    "ncbi_link": "miR-29b: 723963///387223"
  },
  {
    "caption": "C, RB was efficiently deleted in the uterus of mice with uterine deletion of Rb1 (Rb1d/d mice) on day 4 of pregnancy. Scale bar = 100μm. D, RB expression was normal in the ovary of Rb1d/d mice on day 4 of pregnancy. Scale bar = 100μm.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "E, The number of new-born pups was decreased in Rb1d/d dams (n=37 different dams) compared to their littermate controls (Rb1f/f mice, n=20 different dams) (mean ± SEM, Student's t test).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "A-C, Ovulation, fertilization and development of preimplantation embryos were normal in Rb1d/d mice (A&C, mean ± SEM, Student's t test; n=5 mice for each group; B, Fisher's exact test; n=5 mice for each group).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "Number of Ki67-positive cells on day 4 in uterine epithelium of Rb1d/d mice was higher than that of Rb1f/f mice (mean ± SEM, Student's t test; n=5 mice for each group). Scale bar, 100μm; le, luminal epithelium; s, stroma.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "Number of Ki67-positive cells on day 4 in uterine epithelium of Rb1d/d mice was higher than that of Rb1f/f mice (mean ± SEM, Student's t test; n=5 mice for each group). Scale bar, 100μm; le, luminal epithelium; s, stroma.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "F-G, Embryo attachment occurred normally in Rb1d/d mice at 0900h on day 5 (mean ± SEM, Student's t test; n=5 mice for each group). Arrow, implantation site; scale bar = 1 cm.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "H-I, Rb1d/d mice showed higher rate of embryo resorption on day 8 (*P<0.05; Fisher's exact test; n=45 implantation sites for Rb1f/f mice and n=46 implantation sites for Rb1d/d mice). Arrow, implantation site; scale bar = 1 cm.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "J, H&E staining showed embryo resorption in Rb1d/d mice on day 8 of pregnancy. Scale bar = 200 μm; arrowhead, embryo; arrow, broken embryo with blood cell infiltration.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "K, Weight of implantation site was comparable between Rb1f/f and Rb1d/d mice on day 6, but reduced on day 8 in Rb1d/d mice compared to Rb1f/f mice (mean ± SEM, Student's t test; n=6 mice for each group).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "L-M, Expression of Cox2 and Bmp2, markers of decidualization, was comparable in between Rb1d/d and Rb1f/f mice at 0900h on day 6 in implantation sites (mean ± SEM, Student's t test; n=4 mice for each group).",
    "ncbi_link": "Bmp2: 12156
Cox2: 17709
Rb1: 19645"
  },
  {
    "caption": "A, Immunostaining of cytokeratin 8 (CK8), a marker of epithelial cell lineage, showed that epithelial alignment is collapsed and the trophoblast invades the stroma at implantation sites in Rb1f/f mice, while epithelial alignment is persistent and trophoblast invasion into the stroma is compromised in Rb1d/d mice. Scale bar = 200μm; arrowhead, an embryo.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "B, Transmission electron microscopic analyses (TEM) showed that the uterine epithelium surrounding the embryo disappears and the trophoblast contacts directly with the stroma at 2000h on day 5 in Rb1f/f mice, while the uterine epithelium is persistent and the embryo does not attach to the stroma in Rb1d/d mice. Scale bar = 10µm; red dotted line, stroma; green dotted line, luminal epithelium; blue dotted line, trophoblast.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "C, TEM showed that fragmented luminal epithelial cells with cytoplasmic lipid droplets are engulfed by the trophoblast in the control mice (Rb1f/f mice). Scale bar = 2µm. Arrowhead, cytoplasmic fragments engulfed by trophoblast; yellow dotted line circle, cytoplasmic lipid droplets in the luminal epithelium; red dotted line, stroma; green dotted line, luminal epithelium; blue dotted line, trophoblast.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "D, TEM showed that the microvilli, markers of uterine receptivity, were observed at the surface of intact luminal epithelium on day 4 of pregnancy and epithelial cells with cytoplasmic lipid droplets were observed at 2000h on day 5 of pregnancy in the control mice (Rb1f/f mice). Scale bar = 2µm; red dotted line, stroma; green dotted line, luminal epithelium; blue dotted line, trophoblast.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "E, Immunofluorescence of MFG-E8, a marker of programmed cell death, showed that MFG-E8 is not expressed at the implantation sites of Rb1f/f mice at 0900h on day 5 and Rb1d/d mice at 0900h and 2000h on day 5, but is expressed at the implantation sites of Rb1f/f mice at 2000h on day 5. Scale bar = 100μm; blue signal, nuclei stained by DAPI; yellow signal, MFG-E8; arrowhead, embryo.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "A, Serum estradiol-17β (E2) levels on days 4 and 6 of pregnancy were comparable between Rb1f/f and Rb1d/d mice (mean ± SEM, Student's t test; n=4 mice for each group).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "B, Serum P4 levels on days 4 and 6 of pregnancy were comparable between Rb1f/f and Rb1d/d mice. In Rb1d/d mice, pre-implantation P4 treatment on days 2 and 3 increased serum P4 levels on day 4 but did not affect those on day 6 (mean ± SEM, Student's t test; n=4 mice for each group).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "D, Persistent Ki67 expression in the epithelium of Rb1d/d mice on day 4 was recovered by pre-implantation P4 treatment on days 2 and 3. Scale bar = 100μm; le, luminal epithelium; s, stroma. E, Ratio of Ki67-positive epithelial cells in Rb1d/d mice was completely suppressed by pre-implantation P4 supplementation on days 2 and 3. The same data of Rb1f/f and Rb1d/d mice without P4 treatment in Fig 2D were used (mean ± SEM, Student's t test; n=5 different mice for each group). Three different high-powered fields per mouse were analyzed and each of the Ki67-posivie ratios was demonstrated. ",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "G, Resorption rate was reduced on day 8 in Groups 1 (n=41 different implantation sites) and 2 (n=30 different implantation sites), but not in Group 3 (n=40 different implantation sites). The same data of Rb1f/f and Rb1d/d mice without P4 treatment in Fig 2I were used. H&E staining was performed using all sections that shows the implantation sites, and resorption rate was evaluated. *P<0.05 vs Rb1f/f mice; **P<0.05 vs Rb1d/d mice; Fisher's exact test.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "H, Number of pups delivered by Rb1d/d dams was normalized by pre-implantation P4 treatment on days 2 and 3 (Group 2)(mean ± SEM, Student's t test). The same data of Rb1f/f and Rb1d/d dams without P4 treatment in Fig 1E were used. The numbers of pups in 20 Rb1f/f and 37 Rb1d/d dams without P4 treatment and 7 Rb1d/d dams with P4 treatment were evaluated.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "A, pRIP3, a central mediator of necroptosis, was not expressed at the implantation sites of Rb1d/d mice but was expressed at those of Rb1f/f mice at 1500h on day 5. Scale bar = 100μm; blue signal, nuclei stained by DAPI; purple signal, pRIP3; le, luminal epithelium; s, stroma; arrowhead, embryo; green dotted line, luminal epithelium; red dotted line, stroma.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "C, Uterine expression of Tnfα was elevated in the control mice (Rb1f/f mice) on days 5 and 6 compared to on day 4 (mean ± SEM, Student's t test; n=3 mice for each group). As for the uterine samples on days 5 and 6, those with implantation sites were examined.",
    "ncbi_link": "Rb1: 19645
Tnfα: 21926"
  },
  {
    "caption": "D, The implanting embryo and the uterus produced TNFα at the implantation site of both Rb1f/f and Rb1d/d mice. Immunostaining of TNFα at the implantation sites of Rb1f/f and Rb1d/d mice were performed. Scale bar = 100μm; arrowhead, embryo.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "A-B, In vitro analyses using primary mouse uterine epithelial cells demonstrated that TNFα induces the expression of annexin V, a marker of PS presentation at the outer membrane of Rb1f/f epithelial cells but does not in Rb1d/d ones, and P4 restores TNFα-primed annexin V expression in Rb1d/d uterine epithelial cells (mean ± SEM, Student's t test). Using three lines of primary mouse epithelial cells obtained from both Rb1f/fand Rb1d/d mice, the in vivo experiments were performed three times. Each of the annexin V-positive ratios was demonstrated. Scale bar = 100μm; green signal, annexin V.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "C-D, Annexin V assay using primary mouse uterine epithelial cells showed that TNFα administration increases the expression of annexin V in growth-arrested mouse epithelial cells with thymidine treatment, but does not in the control cells (mean ± SEM, Student's t test). Using three lines of primary mouse epithelial cells obtained from both Rb1f/fand Rb1d/d mice, the in vivo experiments were performed three times. Each of the annexin V-positive ratios was demonstrated. Scale bar = 100μm; green signal, annexin V.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "E, The expression of TNF receptor type 2 (TNFR2) was upregulated in growth-arrested epithelial cells with thymidine and P4 supplementation (mean ± SEM, Student's t test). Using three lines of primary mouse epithelial cells obtained from both Rb1f/fand Rb1d/d groups, qPCR was performed in duplicate.",
    "ncbi_link": "Rb1: 19645
TNF receptor type 2: 21938
TNFR2: 21938"
  },
  {
    "caption": "A, In Rb1d/d mice with pre-implantation P4 treatment, the fragmented uterine epithelial cells with the cytoplasmic lipid droplets were engulfed by the trophoblast cells. Scale bar = 2µm. Arrowhead, cytoplasmic fragments engulfed by trophoblast; dotted line circle, lipid droplets in the cytoplasm; tr, trophoblast; le, luminal epithelium; s, stroma; red dotted line, stroma; green dotted line, luminal epithelium; blue dotted line, trophoblast.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "B, Pre-implantation P4 treatment rescued the expression of MFG-E8 on day 5 of pregnancy in Rb1d/d uteri. Scale bar = 100μm. Blue signal, nuclei stained by DAPI; yellow signal, MFG-E8; le, luminal epithelium; s, stroma; arrowhead, embryo. C, Pre-implantation P4 treatment recovered the expression of pRIP3, a mediator of necroptosis, on day 5 of pregnancy in Rb1d/d uteri. Scale bar = 100μm; blue signal, nuclei stained by DAPI; purple signal, pRIP3; le, luminal epithelium; s, stroma; arrowhead, embryo. ",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "A, RB was efficiently deleted in the uterine epithelium of uterine epithelium-specific conditional knockout mice (Rb1 eKO mice). Scale bar = 100μm. Rb1 eKO mice, Rb1loxP/loxPLtfCre/+ mice; Rb1 eControl mice (littermate controls of Rb1 eKO mice), Rb1loxP/loxP mice; le, luminal epithelium; s, stroma.",
    "ncbi_link": "loxP: 
Cre: 2777477
Ltf: 17002
Rb1: 19645"
  },
  {
    "caption": "B, Number of new-born pups was comparable between Rb1 eKO and eControl dams (mean ± SEM, Student's t test; n=10 different dams for each group).",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "C, The expression patterns of Ki67 on day 4 in uterine epithelium were comparable between Rb1 eKO and Rb1 eControl mice. Scale bar, 100μm; le, luminal epithelium; s, stroma.",
    "ncbi_link": "Rb1: 19645"
  },
  {
    "caption": "Raji   cells expressing HIV-1YU-2 envelope  (Raji-Env) or Raji  control cells (Raji-Ctr) were incubated with 10-1074  or scFv10-1074  or with controls (only secondary antibody or streptavidin  added). Binding  of  10-1074 and scFv10-1074  was assessed by flow cytometry  using a BV421-conjugated anti-IgG Fc antibody or streptavidin, respectively. The numbers indicate the % of cells with bound antibody. One experiment is shown.",
    "ncbi_link": "envelope: "
  },
  {
    "caption": "Primary CD4 T cells  infected with HIV-1NL4-3-eGFP and uninfected CD4 T cells  were incubated with NHS   and the indicated antibodies or BiCEs in presence of an HIV-inhibitor. The frequency of eGFP+ cells was analyzed by flow cytometry at the indicated  time points. The numbers indicate the % of eGFP+ cells. One representative donor is shown.",
    "ncbi_link": "eGFP: "
  },
  {
    "caption": "Proportion of CD11b+F4/80+ and RORγt+/CD45+lin- cells was analyzed in colonic LP cells and mLNs among tumor-bearing WT and Dectin-3-/- mice by flow cytometry.",
    "ncbi_link": "Dectin-3: 17474"
  },
  {
    "caption": "Relative expression of Il-6, Il-22, Cxcl1 and Il-17a in LP cells from tumor-bearing WT and Dectin-3-/- mice were detected using qPCR.",
    "ncbi_link": "Dectin-3: 17474
Cxcl1: 14825
Il-17a: 16171
Il-22: 50929
Il-6: 16193"
  },
  {
    "caption": "mRNA expressions of IL-22, β-defensin, Reg3g, and Cxcl1 in LP cells were detected by qPCR.",
    "ncbi_link": "Cxcl1: 14825
β-defensin: 13214
IL-22: 50929
Reg3g: 19695"
  },
  {
    "caption": "LP cells and mLNs were isolated from each mouse and were culture for 48h. Production of IL-22 in LP cells and mLNs were detected by ELISA. LP cells were isolated from each mouse and were culture for 48h. Expression of Il-17 in LP cells were detected by qPCR. Production of IL-17 in LP cells were detected by ELISA.",
    "ncbi_link": "Il-17: 56069///16171"
  },
  {
    "caption": "WT and Dectin-3-/- mice were intraperitoneally treated with anti-IL22 antibody or anti-IgG antibody as control during AOM-DSS administration (n=5, each group). Mice were euthanized on Day 100, tumor number, tumor size, and tumor load in colons were measured.",
    "ncbi_link": "Dectin-3: 17474"
  },
  {
    "caption": "WT and Dectin-3-/- mice were intraperitoneally treated with anti-CD90 antibody or anti-IgG antibody during AOM-DSS administration (n=5, each group). Mice were euthanized on Day 100, feces were collected in colon from each mouse. Total fungal burden in feces were quantified using 18S rDNA qPCR.",
    "ncbi_link": "Dectin-3: 17474"
  },
  {
    "caption": "Primary macrophages were isolated from LP cells in WT and Dectin-3-/- tumor-bearing mice. mRNA expression of glycolysis-relative genes detected by using qPCR.",
    "ncbi_link": "Dectin-3: 17474"
  },
  {
    "caption": "BMDMs acquired from WT and Dectin-3-/- mice were stimulated with C.albicans for 24h. Cytokine and chemokine production of BMDMs were detected using multiplex cytokine assay.",
    "ncbi_link": "Dectin-3: 17474"
  },
  {
    "caption": "WT-derived BMDMs were stimulated with C.albicans, curldan, or α-mannan in combination with or without 2-DG (2.5mM) for 24h. mRNA expression of Il-7 were detected by using qPCR. BMDMs were acquired from WT and HIF-1-/- mice and were stimulated with C.albicans, curldan, or α-mannan for 24h. mRNA expression of Il-7 were detected by using qPCR.",
    "ncbi_link": "HIF-1: 15251
Il-7: 16196"
  },
  {
    "caption": "Primary ILC3 cells were sorted from colonic LP cells and were stimulated with indicated cytokines. Productions of IL-22 were detected by ELISA. mRNA expressions of Il-22 were detected by qPCR.",
    "ncbi_link": "Il-22: 50929"
  },
  {
    "caption": "BMDMs were stimulated with C.albicans for 24h and the supernatant was isolated and added to primary ILC3 cells. (1) Supernatant from BMDMs without stimulation. (2) Supernatant from BMDMs with stimulation of C.albicans. (3) Supernatant from BMDMs with stimulation of C.albicans and IL-7 antibody. Productions of IL-22 by ILC3 cells were detected by ELISA. mRNA expressions of Il-22 in ILC3 cells were detected by qPCR.",
    "ncbi_link": "Il-22: 50929"
  },
  {
    "caption": "Primary ILC3 cells were sorted in LPs from STAT3fl/fl and STAT3fl/fl VillinCre mice and were stimulated with IL-7. Productions of IL-22 were detected by ELISA. mRNA expressions of Il-22 in ILC3 cells were detected by qPCR.",
    "ncbi_link": "Cre: 2777477
Il-22: 50929
STAT3: 6774
Villin: 22349"
  },
  {
    "caption": "HEK293T cells were transiently transfected with the indicated expression constructs (Ctl or AhR) and were stimulated with (IL-7 group) or without IL-7 (none group). ChIP analysis of the interaction of AhR and STAT3 to binding sites in the il22 promoter with or without IL-7, respectively.",
    "ncbi_link": "AhR: 196
il22: 50616"
  },
  {
    "caption": "EL4 cells were transduced with retroviruses encoding AhR and STAT3. IL-22 mRNA expression was analyzed by qPCR.",
    "ncbi_link": "AhR: 196
IL-22: 50929
STAT3: 20848"
  },
  {
    "caption": "Patients with colon cancer were divided into four groups based on tumor stage. mRNA expressions of Dectin-3 in tumor tissues were detected by qPCR. The box represents the 25th to 75th percentile, and the whisker plots represent the minimum and maximum percentiles. Patients with colon cancer were divided into two groups based on fungal burden in the feces. mRNA expressions of Dectin-3 was compared between these two groups.",
    "ncbi_link": "Dectin-3: 338339"
  },
  {
    "caption": "Tumor tissues were stained for IL-22 and p-STAT3. The percentages of IL-22-positive and p-STAT3-positive cells were quantified. mRNA expressions of IL22 and STAT3 were detected by qPCR. Scale bars, 25 µm.",
    "ncbi_link": "IL22: 50616
STAT3: 6774"
  },
  {
    "caption": "Co-immunoprecipitation (Co-IP) analysis of interactions between FLAG-tagged Stx16/Vti1a/Stx6 and EGFP-tagged LC3B or GABARAP overexpressed in HEK293T cells. * indicates mouse IgG heavy chain of precipitated mouse-anti-FLAG antibody.",
    "ncbi_link": "EGFP: 
FLAG: 
GABARAP: 11337
LC3B: 81631
Stx16: 8675
Stx6: 10228
Vti1a: 143187"
  },
  {
    "caption": "WT or STX17-knockout (STX17KO) HeLa cells were starved with or without the presence of bafilomycin A1 (Baf A1, 100 nM) for 2 h, and cell lysates were subjected to Western blot analysis of LC3B and p62.   Quantifications of LC3B-II levels normalized to β-actin from cells treated as in (A); Data shown as means ± SEM of LC3B-II and β-actin ratios, n = 3; *, p < 0.05 (one-way ANOVA).   ",
    "ncbi_link": "STX17: 55014"
  },
  {
    "caption": "WT, STX16KO, STX17KO or STX16/STX17 double KO (STX16/STX17DKO) HeLa cells were starved with or without the presence of Baf A1 (100 nM) for 2 h, and cell lysates were subjected to Western blot analysis of LC3B.   Quantifications of LC3B-II levels normalized to β-actin from (C); Data shown as means ± SEM of LC3B-II and β-actin ratios, n = 3; †, not significant; **, p < 0.01 (one-way ANOVA).   ",
    "ncbi_link": "STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT or STX16/STX17DKO HeLa cells were starved in EBSS for 2 h, and subjected to ultrastructural analysis of the autophagic vesicles (AV) with electron microscopy. AVi: initial autophagic vacuoles; AVd: degradative autophagic vacuoles; G: Golgi apparatus. Image acquisition and counting as in Methods. Scale bars, 1 μm and 0.5 µm (top sections).   Quantifications of autophagic vesicles in WT and STX16/STX17DKO HeLa cells treated as (E); Data shown as means ± SEM of AV profiles relative to cytoplasmic area; †, not significant; *, p < 0.05 (two-way ANOVA). AV profiles from 47 images of each samples were counted.   ",
    "ncbi_link": "STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT or STX16/STX17DKO HeLa-YFP-Parkin cells were treated with CCCP (10 µM) or oligomycin A (5 µM) and antimycin A (10 µM) (OA) for 16 hours, and subjected to high-content microscopy (HCM) analysis of mitochondria clearance. Masks: blue, nuclei; red, mitochondria stained with mitochondrial DNA (mtDNA) antibody. Scale bar: 20 µm.   Quantifications of mtDNA by object count or total area per cell in WT or STX16/STX17DKO HeLa-YFP-Parkin cells treated as in (A); Data shown as means ± SEM of mtDNA object count (upper panel) or object total area (lower panel) per cell; minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; **, p < 0.01 (two-way ANOVA).   ",
    "ncbi_link": "YFP: 
Parkin: 5071
STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT or STX16/STX17DKO Huh7 cells were treated with H2O2 (0.4 mM) for indicated time points, and autophagic clearance of peroxisomes was measured by the protein levels of PMP70, PEX14 and p62.   Quantifications of peroxisomal proteins PMP70 and PEX14 for WT or STX16/STX17DKO Huh7 cells treated as in (C); Data shown as means ± SEM of PEX14 or PMP70 and β-actin ratios, n = 3; †, not significant; *, p < 0.05; **, p < 0.01 (two-way ANOVA).   ",
    "ncbi_link": "STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT, STX16KO, STX17KO or STX16/STX17DKO THP-1 cells were infected with Mycobacterium tuberculosis (Mtb), followed by starvation to induce autophagy. Autophagic clearance of infected Mtb was measured by Mtb colonies grown on Middlebrook 7H11 agar plates; Data shown as means ± SEM of Mtb colonies, n = 4; *, p < 0.05; **, p < 0.01 (two-way ANOVA).",
    "ncbi_link": "STX16: 8675
STX17: 55014"
  },
  {
    "caption": "Validation of STX16/STX17 DKO by Western blot analysis in HEK293 cells stably expressing RPS3-Keima (left panel) and HCT116 cells stably expressing RPL28-Keima (right panel).",
    "ncbi_link": "Keima: 
RPL28: 
RPS3: 
STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT or STX16/STX17DKO HEK293 RPS3-Keima cells were cultured in full medium or starved for 8 hours, and subjected to HCM analysis of Keima puncta accumulated in autolysosomes with the excitation wavelength at 560 nm. Masks: white, cells identified based on nuclei; red, Keima puncta detected with the excitation and emission wavelengths of 560 nm and 620 nm, respectively; lower panel shows Keima puncta without masks. Scale bar: 20 µm.   Quantifications of autolysosomal Keima puncta in WT or STX16 /STX17DKO HEK293 RPS3-Keima cells treated as in (C). Data shown as means ± SEM of Keima puncta per cell, minimum 1000 cells were counted each well from at least 12 wells, 3 independent experiments; **, p < 0.01 (two-way ANOVA).  ",
    "ncbi_link": "Keima: 
RPS3: 
STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT or STX16/STX17DKO HCT116 RPL28-Keima cells were cultured in full medium or starved for 8 hours, and subjected to HCM analysis of Keima puncta accumulated in autolysosomes with the excitation wavelength at 560 nm. Masks: white, cells identified based on nuclei; red, Keima puncta detected with the excitation and emission wavelengths of 560 nm and 620 nm, respectively; lower panel shows Keima puncta without masks. Scale bar: 20 µm.   Quantifications of autolysosomal Keima puncta in WT or STX16/STX17DKO HCT116 RPL28-Keima cells treated as in (E). Data shown as means ± SEM of Keima puncta per cell, minimum 1000 cells were counted each well from at least 12 wells, 3 independent experiments; †, not significant; **, p < 0.01 (two-way ANOVA).   ",
    "ncbi_link": "Keima: 
RPL28: 
STX16: 8675
STX17: 55014"
  },
  {
    "caption": "(A) WT or STX16KO HeLa cells were starved in EBSS for 2 h and subjected to HCM analysis of LAMP2 and LC3 puncta. Masks: white, cells identified based on nuclei; red, LC3 puncta; green, LAMP2 puncta; yellow, overlap of LC3 and LAMP2. Scale bar: 20 µm.",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "(B-D) Quantifications of LC3 puncta per cell (B), LC3 and LAMP2 overlap area per cell (C), and LAMP2 puncta per cell (D) in WT or STX16KO cells treated Data shown as means ± SEM of puncta or overlap area per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; *, p < 0.05; **, p < 0.01 (two-way ANOVA).",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "(E) Western blot analysis of LAMP1 and LAMP2 protein levels in WT and separate clones of STX16KO HeLa, Huh7, and U2OS cells.",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "(F) Western blot analysis of LAMP2 protein levels in WT and separate clones of STX6KO or VTI1AKO HeLa cells.",
    "ncbi_link": "STX6: 10228
VTI1A: 143187"
  },
  {
    "caption": "(G) Time course of mTOR inactivation during EBSS starvation in WT vs. STX16KO HeLa cells analyzed by Western blotting for mTOR substrates ULK1 and 4E-BP1.",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "(H) WT or STX16KO HeLa cells were starved in EBSS for 1 h and subjected to HCM analysis of mTOR puncta. Masks: white, cells identified based on nuclei; red, mTOR puncta. Scale bar: 20 µm. (I) Quantifications of mTOR puncta in WT or STX16KO cells treated as in (H). Data shown as means ± SEM of mTOR puncta per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; **, p < 0.01 (two-way ANOVA). ",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "WT or STX16KO HeLa cells were starved in EBSS for 1 h, followed by starvation with the presence of LysoTracker Red DND-99 (LTR) (100 nM) for additional 30 min, and subjected to HCM analysis of LTR. Scale bar: 20 µm.   Quantifications of LTR count per cell or total area per cell in WT and STX16KO HeLa cells treated as in (A). Data shown as means ± SEM of LTR puncta per cell or object total area per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; †, not significant (two-way ANOVA).   ",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "WT or STX16KO HeLa cells were starved in EBSS for 1 h, followed by starvation with the presence of LTR (100 nM) for additional 30 min, and subjected to HCM analysis of the colocalization between LTR and TGN46. Masks: white, cells identified based on nuclei; red, LTR puncta; green, TGN46 puncta; yellow, overlap between LTR and TGN46. Scale bar: 20 µm.   Quantifications of overlaps between LysoTracker Red and TGN46 in WT and STX16KO cells treated as in (C). Data shown as means ± SEM of LTR and TGN46 overlap area per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; **, p < 0.01 (two-way ANOVA).   ",
    "ncbi_link": "STX16: 8675"
  },
  {
    "caption": "WT or STX16/STX17DKO HeLa cells were starved in EBSS for 2 h, and subjected to ultrastructural analysis of the Golgi apparatus with electron microscopy. VF of Golgi: volume fraction of Golgi relative to total cytoplasmic area. Scale bar, 2 μm. Red arrows indicate Golgi apparatus.",
    "ncbi_link": "STX16: 8675
STX17: 55014"
  },
  {
    "caption": "WT, LC3TKO, GABARAPTKO or HexaKO HeLa cells were starved in EBSS for 90 min and subjected to HCM analysis of overlaps between LAMP2 and Stx16. Masks: white, cells identified based on nuclei; green, LAMP2 puncta; red, Stx16 puncta; yellow, overlap of LAMP2 and Stx16. Scale bar: 20 µm.",
    "ncbi_link": "GABARAP: 11337
Hexa: 3073
LC3: 81631///440738///84557"
  },
  {
    "caption": "Quantifications of overlaps between LAMP2 and Stx16 in WT, LC3TKO, GABARAPTKO or HexaKO HeLa cells treated Data shown as means ± SEM of LAMP2 and Stx16 overlap area per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; *, p < 0.05; **, p < 0.01 (one-way ANOVA).",
    "ncbi_link": "GABARAP: 11337
Hexa: 3073
LC3: 81631///440738///84557"
  },
  {
    "caption": "Quantifications of overlaps between LBPA and Stx16 in WT, LC3TKO, GABARAPTKO or HexaKO HeLa cells grown in full medium or treated Data shown as means ± SEM of LBPA and Stx16 overlap area per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; *, p < 0.05; **, p < 0.01 (one-way ANOVA).",
    "ncbi_link": "GABARAP: 11337
Hexa: 3073
LC3: 81631///440738///84557"
  },
  {
    "caption": "WT, LC3TKO, GABARAPTKO or HexaKO HeLa cells were starved in EBSS for 1 hour, followed by starvation with the presence of LTR (100 nM) for additional 30 min, and subjected to HCM analysis of LTR. Scale bar: 20 µm.",
    "ncbi_link": "GABARAP: 11337
Hexa: 3073
LC3: 81631///440738///84557"
  },
  {
    "caption": "Quantifications of LTR puncta in WT, LC3TKO, GABARAPTKO or HexaKO HeLa cells treated Data shown as means ± SEM of LTR puncta per cell, minimum 500 cells were counted each well from at least 12 wells, 3 independent experiments; †, not significant; *, p < 0.05; **, p < 0.01 (one-way ANOVA).",
    "ncbi_link": "GABARAP: 11337
Hexa: 3073
LC3: 440738///81631///84557"
  },
  {
    "caption": "a. Normalized expression of Tox in CA1sp1, Leng8 in CA3sp3, Hecw1 in DG3, and Thra in Astro1 show variable expression throughout the hippocampus. Scale bar is 500 microns. spDEGs were computed by comparing the true variance in gene expression between cell subtype neighborhoods to that of randomly permuted cell (sub)type neighborhoods.",
    "ncbi_link": "Hecw1: 94253
Leng8: 232798
Thra: 21833
Tox: 252838"
  },
  {
    "caption": "A. Expression of Dot1L in different B-cell populations (Shi et al., 2015). B1: B1 cells, MZB: marginal zone B, FOB: follicular B, GCB: germinal center B, SPLPB: spleen plasma blast, SPLPC: spleen plasma cells, and BMPC: Bone marrow plasma cells. Expression is shown as transcript per million (TPM). Results represent the data from two biological replicates except SPLPB and BMPC which lack replicates (WT; n=2)..Bars indicate mean values.",
    "ncbi_link": "Dot1L: 208266"
  },
  {
    "caption": "B. Differential (FDR < 0.05) expression of Bach2, Prdm1 (encoding BLIMP-1), Cd138 (a plasma-cell marker) and Myc transcripts as indicated by counts per million after TMM normalization from WT and KO. Data was generated from three independent biological replicates for each genotype. Bars and error bars indicate mean ± SD. Statistical significance is indicated by FDR after the Benjamini-Hochberg multiple testing correction performed by edgeR package using R language.",
    "ncbi_link": "Bach2: 12014
Myc: 17869
Prdm1: 12142"
  },
  {
    "caption": "D. H3K79me2 methylation at the Ezh2 locus from WT activated and naïve B cells, as determined by reads per genomic content (RPGC). Data represent three independent biological replicates.",
    "ncbi_link": "Ezh2: 2146"
  },
  {
    "caption": "(a) Ba/F3 cells expressing myrPI(3)K-ER, myrPKB-ER, FOXO3(A3)-ER or FOXO4(A3)-ER were stimulated with 4-OHT for 4 h (myrPI(3)K-ER, myrPKB-ER) or 8 h (FOXO3(A3)-ER and FOXO4(A3)-ER) and microarray analyses were performed. Shown are the fold changes relative to control cells for glutamine synthetase (GS), Mxi1 and Pink1. Data are represented as mean values of one experiment performed in quadruplicate.",
    "ncbi_link": "PKB: 11651///11652
ER: 13982
FOXO3: 56484
FOXO4: 54601
glutamine synthetase: 14645
Mxi1: 17859
PI(3)K: 18706
Pink1: 68943"
  },
  {
    "caption": "(b) Ba/F3 cells expressing either myrPI(3)K-ER or myrPKB-ER were cytokine starved overnight and stimulated with 4-OHT. Relative mRNA levels of glutamine synthetase were analysed using quantitative rtPCR. Data are represented as mean ± s.e.m. normalized for B2M (n=4). *P0.05, **P0.01.",
    "ncbi_link": "PKB: 11651///11652
ER: 13982
glutamine synthetase: 14645
PI(3)K: 18706"
  },
  {
    "caption": "(c) Ba/F3 cells expressing either myrPI(3)K-ER or myrPKB-ER were cytokine starved overnight and stimulated with 4-OHT. Cell lysates were analysed for protein levels of phospho-FOXO3 (T32), glutamine synthetase, p27 and actin. Shown are representative blots (n=4).",
    "ncbi_link": "PKB: 11651///11652
ER: 13982
PI(3)K: 18706"
  },
  {
    "caption": "(d) Ba/F3 cells expressing either FOXO3(A3)-ER or FOXO4(A3)-ER were stimulated with 4-OHT in the presence of mIL-3. Relative mRNA levels of glutamine synthetase were analysed using quantitative rtPCR. Data are represented as mean ±  s.e.m. values normalized for B2M (n=3). **P0.01.",
    "ncbi_link": "ER: 13982
FOXO3: 56484
FOXO4: 54601
glutamine synthetase: 14645"
  },
  {
    "caption": "(e) Ba/F3 cells expressing either FOXO3(A3)-ER or FOXO4(A3)-ER were stimulated with 4-OHT in the presence of mIL-3. Cell lysates were analysed for protein levels of glutamine synthetase, p27 and actin. Shown are representative blots (n=3).",
    "ncbi_link": "ER: 13982
FOXO3: 56484
FOXO4: 54601"
  },
  {
    "caption": "(h) FOXO1,3,4−/− MEFs and wild-type MEFs were incubated with LY294002 (10 μM) for the indicated times. Cell RNA was isolated and relative mRNA levels of glutamine synthetase were analysed using quantitative PCR. Data are represented as mean values normalized for B2M (n=2). Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "FOXO1: 56458
glutamine synthetase: 14645"
  },
  {
    "caption": "(a) Ba/F3 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT and actinomycin D (1 μg ml−1) or dimethylsulphoxide (DMSO) as a control in the presence of mIL-3 for 16 h. Cell lysates were analysed for protein levels of glutamine synthetase (GS), p27 and actin. Shown are representative blots (n=3).",
    "ncbi_link": "ER: 13982
FOXO3: 56484"
  },
  {
    "caption": "(b) Glutamine synthetase reporter plasmids carrying mutations in putative FOXO-binding sites were transfected in HEK293 cells together with Renilla and FOXO3(A3) as indicated. Luciferase activity was measured 40 h after transfection. Data are depicted as relative luciferase units (RLU) compared with the control. Shown are mean ± s.e.m. values (n=3)",
    "ncbi_link": "Renilla: 
FOXO3: 56484"
  },
  {
    "caption": "(a) DLD1 cells expressing FOXO3(A3)-ER were transiently transfected with GFP-ULK2 and stimulated with 4-OHT and MSO for 24 h in glutamine-free DMEM containing 0.1% FCS. Cells were stained for LC3 and analysed by confocal microscopy. Shown are representative pictures (n=3). Scale bars, 20 μm.",
    "ncbi_link": "ER: 2099
FOXO3: 2309
ULK2: 9706"
  },
  {
    "caption": "(d) DLD1 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT. Cell lysates were analysed for protein levels of glutamine synthetase, p27 and actin. Shown are representative blots (n=4).",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(e) The osteosarcoma cell line U2OS expressing FOXO(A3)-ER was stimulated with 4-OHT, cells were lysed and equal amounts of proteins were analysed for levels of glutamine synthetase and actin.",
    "ncbi_link": "ER: 2099"
  },
  {
    "caption": "(f) MSCs expressing FOXO(A3)-ER were stimulated with 4-OHT, cells were lysed and equal amounts of proteins were analysed for levels of glutamine synthetase and actin. Shown are representative blots (n=3).",
    "ncbi_link": "ER: 2099"
  },
  {
    "caption": "(g) Wild-type, daf-2 and daf-16 mutant worms were synchronized to L1 by hypochlorite treatment and were placed on nematode growth medium agar plates. After five days worms were lysed in imidazole and analysed for glutamine synthetase activity.",
    "ncbi_link": "daf-16: 172981
daf-2: 175410"
  },
  {
    "caption": "(h) Wild-type N2 worms or daf-2 mutants were synchronized to L1 by hypochlorite treatment and placed on nematode growth medium plates with or without bacteria expressing DAF-16 double-stranded RNA. After five days worms were lysed in imidazole and analysed for glutamine synthetase activity. (g,h) Shown are the means of five independent plates for each condition. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "DAF-16: 172981
daf-2: 175410"
  },
  {
    "caption": "(a) Ba/F3 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT in the presence of mIL-3. Cell lysates were analysed for glutamine synthetase (GS) activity in an enzyme assay (left). In addition, the expression of glutamine synthetase, p27 and actin was determined using western blot (right). Shown are the mean ± s.e.m. (n=3) and representative blots of these experiments. **P0.01.",
    "ncbi_link": "ER: 13982
FOXO3: 56484"
  },
  {
    "caption": "(b) Ba/F3 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT for 16 h in the presence of mIL-3 together with MSO, as indicated. Cell lysates were analysed for glutamine synthetase activity in an enzyme assay (left). Furthermore the expression levels of glutamine synthetase, p27 and actin were determined using western blot (right). Shown are the mean ±  s.e.m. (n=3) and representative blots of these experiments. *P0.05, **P0.01.",
    "ncbi_link": "ER: 13982
FOXO3: 56484"
  },
  {
    "caption": "(c) Ba/F3 cells expressing myrPI(3)K-ER were cytokine-starved overnight. The next day, cells were washed in PBS and put in a medium without serum, with or without 4-OHT. At the times indicated, medium samples were taken and analysed for amino acid levels by high-performance liquid chromatography. Cells were lysed and equal amounts of protein were analysed by western blotting for levels of phospho-PKB (S473), phospho-FOXO3 (T32) and actin (inset). Shown are the mean of relative amino acid levels, compared with t=0 (n=2), and representative blots of these experiments.",
    "ncbi_link": "ER: 13982
PI(3)K: 18706"
  },
  {
    "caption": "(d) Ba/F3 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT in serum-free medium containing mIL-3. The medium was analysed for amino acid levels by high-performance liquid chromatography. Cells were lysed and analysed for protein levels of glutamine synthetase, p27 and actin (inset). Shown are the mean ±  s.e.m. of relative amino acid levels, compared with t=0 (n=4), and representative blots of these experiments. **P0.01. Uncropped images of blots are shown in Supplementary Fig. S7.",
    "ncbi_link": "ER: 13982
FOXO3: 56484"
  },
  {
    "caption": "(a) DLD1 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT with or without MSO. After 24 h, the cells were starved of serum, amino acids and glucose in D-PBS containing the indicated inhibitors and stimulated with amino acids for 10 min. Cell lysates were analysed for protein levels of phospho-S6K (Thr 389) and actin. Shown are representative blots of three independent experiments.",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(b,c) DLD1 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT and MSO (0.25 M) for 24 h in glutamine-free DMEM containing 0.1% FCS. Cells were stained for mTOR and LAMP2 and analysed by confocal microscopy. (b) Shown are representative pictures (n=4). Scale bars, 100 μm. (c) Quantification of co-localization between mTOR and LAMP2 as seen in b. Depicted are the mean ±  s.e.m. of the percentage of co-localized pixels from four experiments. *P0.05, **P0.01.",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(d) DLD1 cells expressing FOXO3(A3)-ER were treated with or without 4-OHT, MSO and BafA1 (200 nM). After 24 h, cell lysates were analysed for protein levels of LC3 and tubulin. Shown are representative blots (n=4).",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(e) DLD1 cells expressing FOXO3(A3)-ER were transfected with glutamine synthetase (GS) siRNA or a non-targeting siRNA and stimulated with 4-OHT in glutamine-free DMEM containing 0.1% FBS. After 24 h, cell lysates were analysed for protein levels of glutamine synthetase, LC3 and actin. Shown are representative blots (n=2)",
    "ncbi_link": "ER: 2099
FOXO3: 2309
glutamine synthetase: 2752"
  },
  {
    "caption": "(f) DLD1 cells expressing FOXO3(A3)-ER were transfected with glutamine synthetasesiRNA or non-template (NT) control siRNA and stimulated with 4-OHT for 16 h. Cells were lysed and equal amounts of proteins were analysed for levels of p62 or glutamine synthetase. Shown are representative blots (n=2).",
    "ncbi_link": "ER: 2099
FOXO3: 2309
glutamine synthetase: 2752"
  },
  {
    "caption": "(a) DLD1 cells expressing FOXO3(A3)-ER were stimulated with 4-OHT and MSO for 24 h in glutamine-free DMEM containing 0.1% FCS. Cells were stained for LC3 and ER and analysed by confocal microscopy. Shown are representative pictures (n=3). Scale bars, 20 μm. (b) Quantification of LC3-positive spots as seen in a using ImageJ software. Depicted are mean ±  s.e.m. of the number of LC3-positive spots divided by the number of DAPI-positive cells (n=4). *P0.05.",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(c) MSCs expressing FOXO3(A3)-ER were treated with or without 4-OHT and BafA1 (100 nM). At the indicated time points, cell lysates were analysed for protein levels of glutamine synthetase (GS), LC3, pS6 (Ser 235/236) and actin. Shown are representative blots (n=2).",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(g) DLD1 cells expressing FOXO3(A3)-ER were transiently transfected with GFP-WIPI-1 and subsequently stimulated with 4-OHT in the presence or absence of MSO in glutamine-free DMEM containing 0.1% FCS or medium without amino acids for 24 h. GFP-WIPI-1 puncta formation analysis was performed by confocal microscopy. Depicted are the percentages of cells positive for GFP-WIPI-1 puncta. Shown are the mean ±  s.e.m. (n=4). *P0.05 and **P0.01. Uncropped images of blots are shown in Supplementary Fig. S8.",
    "ncbi_link": "ER: 2099
FOXO3: 2309
WIPI-1: 55062"
  },
  {
    "caption": "(a) DLD1 cells expressing FOXO3(A3)-ER were transiently transfected with GFP-ULK2 and stimulated with 4-OHT and MSO for 24 h in glutamine-free DMEM containing 0.1% FCS. Cells were stained for LC3 and analysed by confocal microscopy. Shown are representative pictures (n=3). Scale bars, 20 μm.",
    "ncbi_link": "ER: 2099
FOXO3: 2309
ULK2: 9706"
  },
  {
    "caption": "(b) DLD1 cells expressing FOXO3(A3)-ER were transiently transfected with GFP-WIPI-1 and subsequently treated with 4-OHT in the presence or absence of MSO in glutamine-free DMEM containing 0.1% FCS. After 24 h, cells were analysed for GFP and p62 expression by confocal microscopy. Shown are representative pictures (n=3). Scale bar, 20 μm.",
    "ncbi_link": "ER: 2099
FOXO3: 2309
WIPI-1: 55062"
  },
  {
    "caption": "(c) DLD1 cells expressing FOXO3(A3)-ER were treated with 4-OHT and MSO in glutamine-free DMEM containing 0.1% FCS. After 24 h cells were analysed for endogenous Atg12 puncta formation by confocal microscopy. Shown are the mean ± s.d. (n=3). *P0.05.",
    "ncbi_link": "ER: 2099
FOXO3: 2309"
  },
  {
    "caption": "(d) DLD1 cells expressing FOXO(A3)-ER were transfected with glutamine synthetase (GS) siRNA or non-template (NT) control siRNA, and stimulated with 4-OHT for 24 h with or without 3-methyladenine (3-MA). Apoptosis was determined by FACS analysis after labelling cells with annexin V (AxV)-phycoerythrin and DAPI. The graph shows relative fold versus control samples, mean ±  s.e.m. (n=3). *P0.05.",
    "ncbi_link": "ER: 2099
glutamine synthetase: 2752"
  },
  {
    "caption": "B mRNA expression studies. qRT-PCR  studies showed a significant decrease in mRNA level of GFUS by 40.0% (± 9.3%, **p = 0.0010) normalized to a control. Also, expression of SLC35C1  and SLC35C2  were significantly decreased in patient-derived fibroblasts. Data were obtained from fibroblasts; n = 10; experiment was independently repeated 3 times, for statistics an one-way ANOVA was performed. Data information: *p < 0.05; **p < 0.01; ***p<0.001. Bars and error bars represent mean ± SD.",
    "ncbi_link": "GFUS: 7264
SLC35C1: 55343
SLC35C2: 51006"
  },
  {
    "caption": "E Complementation study with patient-derived fibroblasts. Viral infection was used to introduce an empty cloning vector and the wild-type GFUS cDNA in  patient cells, respectively. For analysis lysates of a control cell-line, a control cell-line supplemented with 100 µM fucose, patient  cells, patient cells supplemented with 100 µM fucose, patient cells transfected with an empty vector and patient  cells transfected with wild type GFUS  were analyzed by AAL staining clearly indicating the disease-causing influence of the defective GFUS in the patient. Western blot analysis against  GFUS further showed expression of wildtype-GFUS  protein in the infected patient  derived fibroblasts. Data were obtained from fibroblasts; n = 4; experiment was independently repeated 2 times, for statistics an one-way ANOVA was performed. Data information: *p < 0.05; **p < 0.01; ***p<0.001. Bars and error bars represent mean ± SD. ",
    "ncbi_link": "GFUS: 7264"
  },
  {
    "caption": "A MAGE-A3/6 mRNA levels do not change upon nutrient deprivation. RNA was isolated from HeLa cells treated with EBSS for the indicated times. RT-QPCR analysis was performed to detect both MAGE-A3/6 with a common primer set. Data was normalized to 18S rRNA levels. Quantitation represents average of n=3 with standard deviation shown.",
    "ncbi_link": "MAGE-A3: 4102"
  },
  {
    "caption": "E MAGE-A3/6 protein instability upon nutrient deprivation is not rescued by knockdown of its associated E3 ubiquitin ligase, TRIM28. HeLa cells were treated with control or TRIM28 siRNAs for 6 days before incubation in EBSS for the indicated times.",
    "ncbi_link": "TRIM28: 10155"
  },
  {
    "caption": "I Degradation of MAGE-A3/6 upon nutrient deprivation is dependent on Cul4A/B. HeLa cells were transfected with control siRNAs or siRNAs targeting both Cul4A and Cul4B. 72 hrs after treatment, cells were incubated for the indicated times with EBSS before harvesting and immunoblotting. Note, time 0 samples between two siRNA groups were normalized to more readily discern differences in MAGE-A3/6 degradation upon nutrient deprivation.",
    "ncbi_link": "Cul4A: 8451
Cul4B: 8450"
  },
  {
    "caption": "B MAGE-A3 interacts with DCAF12, but not DCAF5. HeLa cells were transfected with the indicated constructs (Myc-MAGE-A3 and HA-DCAF5 or HA-DCAF12). Two days later cells were treated with complete media or EBSS for 4 hrs. Cells were treated in the presence of 1 µM MLN4924 to stabilize MAGE-A3. Cell extracts were subjected to anti-Myc IP.",
    "ncbi_link": "HA: 
Myc: 
DCAF12: 25853
DCAF5: 8816
MAGE-A3: 4102"
  },
  {
    "caption": "C Nutrient deprivation increases endogenous DCAF12 binding to MAGE-A3. HeLa cells were transfect with Myc-vector or Myc-MAGE-A3 for 48 hrs. Cells were then treated with 10 µM MG132 in complete media, EBSS, or EBSS containing 20 µg/mL insulin for 6 hrs. Cell extracts were subjected to anti-Myc IP.",
    "ncbi_link": "Myc: 
MAGE-A3: 4102"
  },
  {
    "caption": "Knockdown of DCAF12, but not DCAF5, altered MAGE-A3/6 protein levels and partially rescued its instability upon nutrient deprivation. HeLa cells were treated with control, DCAF5 siRNAs for 72 hrs before incubation in complete media or EBSS for the indicated times with or without MLN4924 (1 µM).",
    "ncbi_link": "DCAF12: 25853
DCAF5: 8816"
  },
  {
    "caption": "E Knockdown of DCAF12, but not DCAF5, altered MAGE-A3/6 protein levels and partially rescued its instability upon nutrient deprivation. HeLa cells were treated with control or DCAF12 siRNAs for 72 hrs before incubation in complete media or EBSS for the indicated times with or without MLN4924 (1 µM).",
    "ncbi_link": "DCAF12: 25853
DCAF5: 8816"
  },
  {
    "caption": "F Knockdown of DCAF12 with individual siRNAs blocks MAGE-A3/6 degradation upon nutrient deprivation. HeLa cells were treated with the indicated siRNAs for 72 hrs before incubation in EBSS for the indicated times. Note, time 0 samples between siRNA groups were normalized to more readily discern differences in MAGE-A3/6 degradation upon nutrient deprivation.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "G Ubiquitination of MAGE-A3/6 upon nutrient deprivation is dependent on DCAF12. A375 parental or DCAF12 KO cells were treated with MG132 (10 µM) in complete media or EBSS for 6 hrs. Cell extracts were incubated with control agarose or agarose-TUBE2 to isolate ubiquitinated proteins. Input and pulldown samples were probed for the indicated proteins.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "A Identification of DCAF12 substrates. Control (WT) or DCAF12 knockout (KO) A375 cells were subjected to quantitative TMT proteomics to identify potential DCAF12 targets. MAGE-A proteins (shown in blue) are stabilized in DCAF12 knockout cells.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "B Knockout of DCAF12 rescues degradation of MAGE-A proteins in A375 cells. DCAF12 KO A375 cells were treated with complete media or EBSS before quantitative TMT proteomics. Note MAGE-A genes are not significantly altered by EBSS in DCAF12 KO cells.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "C DCAF12 target proteins are differentially affected by EBSS compared to remainder of the proteome. DCAF12 targets (n=33) identified show significantly greater decrease upon EBSS treatment compared to non-DCAF12 altered genes (n=8243). Average with standard deviation is shown with statistical analysis by student t-test. Asterisks *** indicate p<0.001 (student t-test).",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "E Overexpression of DCAF12 decreases wild-type MAGE-A3, but not MAGE-A3 degron mutant. The indicated constructs were expressed for 48 hrs in HeLa cells before immunoblotting. The MAGE-A3 degron mutant was created ], in which DNYNEPKANQ* were added to the extreme C-term to obscure the DCAF12 degron motif.",
    "ncbi_link": "DCAF12: 25853
MAGE-A3: 4102"
  },
  {
    "caption": "F Analysis of proteomics indicates that MAGE-A1, MAGE-A4, MAGE-A10, and MAGE-A11 are not regulated by nutrient deprivation or DCAF12. Average (n=3) with standard deviation is shown with statistical analysis by student t-test. Asterisks *** indicate p<0.001 (student t-test).",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "G MAGE-A10 and MAGE-A11 are not altered upon nutrient deprivation or DCAF12 deletion. A375 parental or DCAF12 KO cells were treated with EBSS for the indicated times. Cell lysates were probed for the indicated proteins.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "C-D A375 parental or DCAF12 KO cells were transfected with the indicated siRNAs for 72 hrs before treatment with complete media or EBSS for 6 hrs. Cells were then fixed, endogenous LC3 was immunostained, and the number of LC3 puncta were quantitated per cell. Representative images (C) and quantitation of >50 cells from three independent experiments (D) are shown. Scale bar indicates 20 µm. Data information: Asterisks indicate * p<0.05; ** p<0.01; *** p<0.001. ns indicates p>0.05 using student t-test.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "E A375 parental or DCAF12 KO cells were treated Cell lysates were collected and immunoblotted for the indicated antibodies to confirm MAGE-A3/6 depletion and monitor the autophagy adaptor/substrate p62/SQSTM1.",
    "ncbi_link": "DCAF12: 25853"
  },
  {
    "caption": "(c) Activation of the hybridoma (as described in b) by macrophages transfected for 60 h with control (Ctrl) siRNA or Atg5-specific siRNA, then infected for 8 h or 12 h with HSV-1.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": " (f) Activation of the hybridoma (as described in b) by macrophages transfected for 60 h with control siRNA or Atg5-specific siRNA, then infected for 8 h with HSV-1, with (+) or without (−) the addition of rapamycin at 2 h after infection. Results in b,c,e,f are normalized to results obtained for CD8+ T cells stimulated with macrophages infected for 8 h at 37 °C without further treatment (b,e) or infected macrophages treated with control siRNA (c,f) and are presented in arbitrary units. Data are representative of three independent experiments (a,d) or are from three independent experiments (mean and s.e.m. of triplicate samples; b,c,e,f). ",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a-b) eIF4A knockdown in either S2 (a) or Kc167 (b) cells blunts the inactivation of TORC1 upon amino acid removal. Cells were treated with dsRNA targeting GFP as a negative control, or three independent, non-overlapping dsRNAs targeting eIF4A for 5 days and then incubated with complete medium or medium lacking only amino acids for 30 minutes. Representative of 3 biological replicates.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(d) Impaired inactivation of TORC1 in response to eIF4A knockdown is most apparent upon partial depletion of amino acids, caused by removal of amino acid subsets. After 5 days of knockdown, S2 cells were treated for 30 min with either complete Schneider's medium (+aa), Schneider's medium lacking all amino acids (-aa) or various subsets of amino acids, as indicated (where EAA \"essential amino acids\" = H,I,L,K,M,T,W,V). Error bars: std dev. n=3 biological replicates.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(e) Time course of amino-acid removal reveals that eIF4A knockdown Kc167 cells maintain elevated S6K phosphorylation up to the maximum possible timepoint of 60 minutes when the cells start dying (see drop in S6K and tubulin levels). Representative of two biological replicates.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(f) eIF4A mutant larvae have impaired TORC1 inactivation upon shifting to food lacking amino acids. Control (w1118) or eIF4A1006/1013 1st instar larvae were transferred from standard food to plates containing either standard fly food or PBS/1% agarose+2%sucrose for 1h prior to lysis and immunoblot analysis. Two biological replicates are shown. Representative of 3 biological replicates.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(a-a') Although knockdown of eIF4A or eIF3-S2 equally blunt translation of EGFP from an inducible plasmid (a), only knockdown of eIF4A but not eIF3-S2 impairs TORC1 inactivation upon amino acid removal (a'). (a) S2 cells, treated with indicated dsRNAs for 5 days, on day 3 transfected with an inducible EGFP plasmid (pMT-EGFP) and on day 4 induced for 18h. Non-targeting LacZ dsRNA used as a negative control. (a') S2 cells treated with indicated dsRNAs for 5 days, then incubated with medium lacking amino acids for indicated time prior to lysis. Representative of two biological replicates.",
    "ncbi_link": "eIF4A: 33835
eIF3-S2: 33710"
  },
  {
    "caption": "(b) Knockdown of eIF4A, but not other translation initiation factors, blunts TORC1 inactivation upon amino acid withdrawal. Kc167 cells treated with indicated dsRNAs for 4 days and then incubated with complete Schneider's medium or Schneider's medium lacking the indicated amino acids for 30 minutes prior to lysis.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(c) Inhibition of translation with cycloheximide does not block inactivation of TORC1 upon amino acid withdrawal in Kc167 cells. Kc167 cells treated with either eIF4A dsRNA for 4 days, or cycloheximide (50 µg/mL, \"CHX\") for 5 min prior to, as well as during removal of amino acids (-LIVASTQP). CHX treated cells still inactivate TORC1 (compare lanes 8 to 7) whereas eIF4A knockdown cells do not (lanes 14 vs 13). Quantifications of two biological replicates are shown. CHX and eIF4A samples were normalized to their respective control conditions.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(d) Knockdown of eIF4A in Kc167 cells does not prevent a drop in intracellular amino acids levels when amino acids are removed from the medium for 30 min. Quantification of total intracellular amino acids, analyzed in a blinded fashion. Levels of individual amino acids shown in Figure S2D. For CHX samples, cycloheximide (50µg/mL) was added 5 minutes prior to, and during treatment with medium containing or lacking amino acids. Statistical significance tested by ANOVA2 using Scheffé's multiple comparisons method (p<0.05). Error bars: std. dev. n=5.",
    "ncbi_link": "eIF4A: 33835"
  },
  {
    "caption": "(a) Knockdown of eIF4F components (eIF-4E and eIF-4G) partially phenocopy the eIF4A knockdown, leading to elevated TORC1 activity upon amino acid removal (30 min). Knockdown of all other tested translation initiation factors do not cause elevated TORC1 upon amino acid removal (main Figures 1c, 2a' and 2b). Error bars: std. dev. n=3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
eIF-4E: 45525
eIF-4G: 43839"
  },
  {
    "caption": "(b) Quantification of de novo protein synthesis rates by OPP incorporation reveals that eIF4E and eIF4G knockdowns deplete eIF4F function less efficiently than the eIF4A knockdown, explaining why the effects of eIF4E and eIF4G knockdowns on TORC1 activity (panel a) are a bit milder than the eIF4A knockdown. Kc167 cells treated with dsRNA for 4 days then incubated with 20μM Click-it OPP reagent 30min before fixation and fluorescent labeling. Quantification of OPP fluorescence per cell (nuclear count) for two independent experiments is displayed (3 independent images per condition), normalized to the no dsRNA condition. Scale bars: 25µm.",
    "ncbi_link": "eIF4A: 33835
eIF4E: 45525
eIF4G: 43839"
  },
  {
    "caption": "(a) Binding of eIF4G to the Rag GTPases detected by co-immunoprecipitation from Kc167 cells in absence or presence of the chemical cross-linker DSP. Representative of >3 biological replicates.",
    "ncbi_link": "eIF4G: 43839"
  },
  {
    "caption": "(b) Binding between eIF4G and the Rag GTPase complex is mainly mediated by RagC, detected by expressing and immunoprecipitating either RagA or RagC alone. Representative of two biological replicates.",
    "ncbi_link": "RagA: 41071
RagC: 35793"
  },
  {
    "caption": "(c) Interaction between eIF4A and Raptor detected via co-immunoprecipitation of epitope-tagged proteins. Proteins were cross-linked with DSP prior to lysis and immunoprecipitation. Representative of 3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
Raptor: 31543"
  },
  {
    "caption": "(d-d'') eIF4A and Raptor form a complex, detected by proximity ligation assay (PLA). Specificity of the PLA signal was controlled by knocking down either eIF4A or Raptor in Kc167. (d) Representative images. Cells outlined in white. (d') Quantification of number of PLA spots per cell. (n>200. ***p<0.0001, ANOVA1, Dunnett's multiple comparisons test, was performed on log-transformed data, box = +/- 1 quartile, whiskers = max/min). (d'') Immunoblotting to detect efficiency of eIF4A and Raptor knockdowns.",
    "ncbi_link": "eIF4A: 33835
Raptor: 31543"
  },
  {
    "caption": "(a) Knockdown of eIF4A and TSC2 do not elevate TORC1 activity in an additive manner, indicating they act in the same, and not parallel pathways. Whereas knockdown of eIF4A increases TORC1 activity in control Kc167 cells (lanes 1-2 and 5-6), eIF4A knockdown cannot further increase TORC1 activity in TSC2 knockdown cells (lanes 3-4 and 7-8). Error bars: std dev. n=3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
TSC2: 40201"
  },
  {
    "caption": "(b) Activation of TSC2 with the p90RSK inhibitor BI-D1870 rescues the elevated TORC1 activity caused by eIF4A knockdown in Kc167 cells, consistent with TSC2 acting downstream of eIF4A. BI-D1870 leads to inhibition of TORC1 (lanes 1-4) in a TSC2-dependent manner (see also Appendix Figure S5A). Representative of two biological replicates.",
    "ncbi_link": "eIF4A: 33835
TSC2: 40201"
  },
  {
    "caption": "(c) FLAG-eIF4A and TSC2-V5 co-immunoprecipitate in Kc167 cells in the absence of chemical cross-linker. Cells were transfected with FLAG-eIF4A and TSC2-V5 expression vectors and treated with media containing or lacking amino acids for indicated timepoints prior to lysis and anti-FLAG immunoprecipitation. The experiment was performed in absence of the chemical cross-linker DSP. Representative of 3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
TSC2: 40201"
  },
  {
    "caption": "(d) Expression of TSC2-insensitive (S15H or Q63L), but not wild-type (WT) Rheb causes TORC1 activity to remain high upon amino acid removal. Kc167 cells were transfected to express either wild-type or mutant Rheb and then incubated with Schneider's medium either containing or lacking amino acids for 30 minutes. Elevated TORC1 activity can be observed either by looking at phosphorylation of endogenous S6K, or phosphorylation of an HA-tagged S6K that was co-transfected with the Rheb constructs to assay specifically the transfected cells. Representative of two biological replicates.",
    "ncbi_link": "TSC2: 40201
Rheb: 117332"
  },
  {
    "caption": "(b) Binding between eIF4A and NAT1 is regulated by amino acid availability in a TORC1-independent fashion. Co-immunoprecipitation of tagged eIF4A and NAT1 in control Kc167 cells, or cells treated with medium lacking amino acids or supplemented with 20 nM rapamycin for indicated times. Representative of 3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
NAT1: 46020"
  },
  {
    "caption": "(c) Knockdown of NAT1 using 4 independent, non-overlapping dsRNAs leads to reduced TORC1 activity. Kc167 cells, treated with indicated dsRNAs for 4 days and then incubated with medium containing or lacking amino acids for 30 min. Error bars: std. dev. n=3 biological replicates.",
    "ncbi_link": "NAT1: 46020"
  },
  {
    "caption": "(d) eIF4A is epistatic to NAT1 for TORC1 regulation. In the absence of amino acids, eIF4A knockdown cells have elevated TORC1 activity, NAT1 knockdown cells have reduced TORC1 activity, and eIF4A & NAT1 double-knockdown cells have elevated TORC1 activity compared to control cells. Cells were treated with indicated dsRNAs for 4 days and then treated with medium containing or lacking the indicated amino acids for 30 min. Error bars: std. dev. n=3 biological replicates.",
    "ncbi_link": "eIF4A: 33835
NAT1: 46020"
  },
  {
    "caption": "(e) TSC2 is epistatic to NAT1 for TORC1 regulation. As in (d), knockdown of TSC2 rescues the reduced TORC1 activity caused by NAT1 knockdown.",
    "ncbi_link": "TSC2: 40201
NAT1: 46020"
  },
  {
    "caption": "(G) Representative images of NuMA (arrowheads) in centrosomal and acentrosomal cells before and after photobleaching. DMSO- or centrinone-treated HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells were observed. Time after photobleaching (sec) is indicated. Scale bar, 5 μm.",
    "ncbi_link": "NuMA: 4926"
  },
  {
    "caption": "(A) Time-lapse observation of the establishment of bipolarity in acentrosomal cells. HeLa cells expressing EGFP-centrin1 and mCherry-NuMA were observed with a 63× objective. Magenta and green represent mCherry-NuMA and EGFP-centrin1, respectively. Arrowheads indicate the assembling NuMA after NEBD. Two-way arrows indicate the bipolarity. Z-projections of 20 sections, every 1.2 μm. Scale bar, 10 μm. Time zero corresponds to NEBD.",
    "ncbi_link": "centrin1: 
EGFP: 
mCherry: 
NuMA: 4926"
  },
  {
    "caption": "(B) Time-lapse observation of the dynamics of NuMA and chromosomes. Centrinone-treated HeLa cells expressing mCover-NuMA were observed with a 63× objective. Magenta and green represent SiR-DNA and mClover-NuMA, respectively. Arrowheads and two-way arrows indicate the assembling NuMA after NEBD and bipolarity, respectively. Z-projections of 20 sections, every 1.2 μm. Scale bar, 10 μm. Time zero corresponds to NEBD.",
    "ncbi_link": "NuMA: 4926"
  },
  {
    "caption": "(E, F) Time-lapse observation of the structure of NuMA and microtubules upon centrosome removal. Centrinone-treated HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells were observed with a 60× objective. Red and green represent NuMA and SiR-tubulin, respectively. Z-projections of 17 sections, every 1 μm. Scale bar, 5 μm. Time zero corresponds to NEBD. (F) An example of NuMA formed several asters (arrowheads) at the time of NEBD.  ",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(A) NuMA structure upon microtubule depolymerization. Nocodazole-treated HCT116 CMV-OsTIR1 CEP152-mClover-mAID cells were treated with 100 ng/ml nocodazole. Gray, red, green and blue represent α-tubulin, NuMA, CEP152 (mClover) and DNA, respectively. Scale bar, 5 μm.",
    "ncbi_link": "mClover: 
CEP152: 22995"
  },
  {
    "caption": "(B) Immunostaining of DHC1 and NuMA in centrinone-treated HCT116 TetOsTIR1 DHC1-3X-mAID-mClover cells. Gray, green, red and blue represent DHC1 (mClover), GT335, NuMA, and DNA, respectively. Scale bar, 5 μm.",
    "ncbi_link": "mClover: 
DHC1: 25981"
  },
  {
    "caption": "(D) NuMA structure upon DHC1 depletion. Centrinone-treated HCT116 TetOsTIR1 DHC1-3X-mAID-mClover cells were treated with 1 μg/ml doxycycline (Dox) and 500 μM indole-3-acetic acid (IAA). Arrowhead indicates the spindle pole. Green, red, gray and blue represent DHC1 (mClover), NuMA, GT335 and DNA, respectively. Scale bar, 5 μm. (E) Frequency of acentrosomal pole patterns upon DHC1 depletion in (D). Values are mean percentages ± SD. from three independent experiments (N≧24 spindles in each experiment). ( ",
    "ncbi_link": "mClover: 
DHC1: 25981"
  },
  {
    "caption": "(F) The distribution of NuMA upon DHC1 depletion. Arrowheads indicate the presence of NuMA on microtubules. Green, red, and blue represent α-tubulin, NuMA, and DNA, respectively. Scale bars, 5 μm.",
    "ncbi_link": "DHC1: 25981"
  },
  {
    "caption": "(G) Structure of acentrosomal spindle poles upon replacement of endogenous NuMA-mAID-mClover-FLAG with either mCherry-NuMA WT or 5A-3. Arrowheads indicate the assembled NuMA structure. Green, red, gray and blue represent endogenous NuMA (mClover), expressed NuMA (mCherry), GT335 and DNA, respectively. Z-projections of 21 sections, every 1 μm. Scale bar, 5 μm. (H) The number of NuMA structure in (G). Values are mean percentages ± SD. from four independent experiments (N≧15 spindles in each experiment). One-way ANOVA with Tukey's multiple comparisons test was used to obtain a P value.  ",
    "ncbi_link": "FLAG: 
mCherry: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(A, B) Structure of the spindle upon NuMA depletion. Centrinone-treated HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells were treated with 1 μg/ml doxycycline (Dox) and 500 μM IAA. Two-way arrow indicates the bipolarity. Gray, green, red, and blue represent α-tubulin, NuMA (mClover), GT335, and DNA, respectively. Z-projections of 10 sections, every 0.3 μm. Scale bar, 5 μm. (C) Frequency of spindle structure patterns upon NuMA depletion in (A, B). Values are mean percentages ± SD. from three independent experiments (N=30 spindles in each experiment). ( ",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(E) The localization of Eg5 in the spindle upon NuMA depletion. Centrinone-treated HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells were treated with Dox and 500 μM IAA. Gray, green, red, and blue represent Eg5, NuMA (mClover), CP110, and DNA, respectively. Z-projections of 5 sections, every 0.3 μm. Scale bar, 5 μm.",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(F) Structure of the spindle upon Eg5 inhibition. Centrinone-treated HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells were treated with 30 μM monastrol. Gray, green, red, and blue represent α-tubulin, NuMA (mClover), GT335, and DNA, respectively. Z-projections of 5 sections, every 0.3 μm. Scale bar, 5 μm. (G) Frequency of spindle structure patterns upon Eg5 inhibition in (F). Values are mean percentages ± SD. from three independent experiments (N≧23 spindles in each experiment).  ",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(A) Time-lapse observation of the establishment of bipolarity within the acentrosomal spindle pole upon inhibition of Eg5. HeLa cells expressing EGFP-centrin1 and mCherry-NuMA were observed in the presence of 50 μM of monastrol with a 63× objective. Magenta and green represent mCherry-NuMA and EGFP-centrin1, respectively. Arrowheads and two-way arrows indicate the monopolar and bipolar states, respectively. Z-projections of 20 sections, every 1.2 μm. Scale bar, 10 μm. Time zero corresponds to NEBD. (B) The time of bipolarity establishment and being stuck in the monopolar-like state of acentrosomal spindle poles in (A). Each plot shows the cumulative percentage of each event at each time point (N=total 75 cells from two independent experiments). ( ",
    "ncbi_link": "centrin1: 
EGFP: 
mCherry: 
NuMA: 4926"
  },
  {
    "caption": "(C) Time-lapse observation of the dynamics of mClover-NuMA and chromosomes. HeLa cells expressing mClover-NuMA were observed in the presence of SiR-DNA with a 63× objective. Magenta and green represent SiR-DNA and mClover-NuMA, respectively. Arrowheads indicate initial bipolarity in the acentrosomal spindle pole (8 min), dispersed chromosomes (328 min), and the monopolar-like state of the acentrosomal spindle pole (332 min), respectively. Z-projections of 20 sections, every 1.2 μm. Scale bar, 10 μm. Time zero corresponds to NEBD. (D) The time of bipolarity establishment and being stuck in the monopolar-like state of acentrosomal spindle poles in (C). Each plot shows the cumulative percentage of each event at each time point (N=total 35 cells from three independent experiments).  ",
    "ncbi_link": "mClover: 
NuMA: 4926"
  },
  {
    "caption": "(A) Structure of the spindle upon NuMA and Eg5 inhibition. HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells with 2-centrosomes were treated with 1 μg/ml doxycycline (Dox), 500 μM IAA and monastrol. Green, red, and blue represent NuMA (mClover), α-tubulin, and DNA, respectively. Z-projections of 10 sections, every 0.3 μm. Scale bar, 5 μm. (B) Frequency of spindle structure patterns upon NuMA depletion and Eg5 inhibition in (A). Values are mean percentages ± SD. from three independent experiments (N≧22 spindles in each experiment). ( ",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(C) The localization of Eg5 in the spindle upon NuMA depletion. HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells with 2-centrosomes were treated with 1 μg/ml doxycycline Dox and 500 μM IAA. Gray, green, red, and blue represent α-tubulin, NuMA (mClover), Eg5 and DNA, respectively. Z-projections of 5 sections, every 0.3 μm. Scale bar, 5 μm.",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "(D) Time-lapse observation of the establishment of spindle bipolarity upon NuMA depletion. HCT116 TetOsTIR1 NuMA-mAID-mClover-FLAG cells with 2-centrosomes were treated with 1 μg/ml Dox and 500 μM IAA and observed with a 40× objective. Red and green represent SiR-tubulin and NuMA, respectively. Z-projections of 14 sections, every 2 μm. Scale bar, 10 μm. Time zero corresponds to NEBD. (E) The time required for the initial establishment of spindle bipolarity in (D). Line and error bars represent the mean and SD. (N≧60 cells from two independent experiments). The Mann-Whitney U test (two-tailed) was used to obtain a P value.  ",
    "ncbi_link": "FLAG: 
mClover: 
NuMA: 4926"
  },
  {
    "caption": "A cdc14‐3 temperature‐sensitive cells reconstituted with CDC14 or CDC14‐NLS were released from a G1 arrest at the restrictive temperature and stained for Cdc14 and the spindle (Tub1) once cells had reached late anaphase.",
    "ncbi_link": "CDC14: 850585
cdc14: 850585"
  },
  {
    "caption": "B Wild‐type, cdc14‐3, +CDC14 and +CDC14‐NLS cells were released from an α‐factor‐induced G1 arrest and re‐arrested in the next G1. Samples were harvested at the indicated time points and stained with DAPI and for the nucleolar protein Nop1 (n > 100). Photographs of examples of cells without (top) and with (bottom) rDNA segregation defects at 80 min after release are shown together with quantification over time.",
    "ncbi_link": "cdc14: 850585
CDC14: 850585"
  },
  {
    "caption": "A +CDC14 and +CDC14‐NLS cells were grown at 35.5°C for 5 h and sonicated, and differential interference contrast (DIC) images were acquired.",
    "ncbi_link": "CDC14: 850585"
  },
  {
    "caption": "C Cells expressing the plasma membrane marker GFP‐Spo2051-91, exemplifying the indicated bud neck phenotypes and stages of cytokinesis.D Bud neck phenotypes of synchronized GFP‐Spo2051-91‐expressing +CDC14 or +CDC14‐NLS cells during the progression of a cell cycle (n > 75).",
    "ncbi_link": "CDC14: 850585"
  },
  {
    "caption": "E +CDC14 or +CDC14‐NLS cells expressing Spc42‐YFP and GFP fusions with the indicated cytokinetic protein were synchronized in G1 using α‐factor. Upon release at 35.5°C, cells were imaged every 2 min and the time from anaphase onset to the indicated events was recorded. Error bars represent SD; Student's t‐test was applied to analyze differences between the indicated conditions; **P ≤ 0.01; ****P ≤ 0.0001. For representative image sequences, see Supplementary Fig S2C.",
    "ncbi_link": "CDC14: 850585"
  },
  {
    "caption": "A MET3pr‐CDC20cdc15‐as1 cells were arrested in metaphase by Cdc20 depletion and subsequently treated with 1NM‐PP1 to inhibit Cdc15‐as1. Cells were released from the metaphase arrest by Cdc20 re‐induction (left graph), or Cdc14 and/or Sic1 expression were induced from the GAL1 promoter while cells remained arrested (right graph). The fraction of large‐budded cells after spheroplastation (n = 100) was quantified. Representative photographs 120 min after galactose addition are shown. Scale bar, 10 μm.",
    "ncbi_link": "Cdc15‐as1: 
cdc15‐as1: 
Cdc14: 850585
Cdc20: 852762
CDC20: 852762
GAL1: 852308
MET3: 853466
Sic1: 850768"
  },
  {
    "caption": "B As (A), the plasma membrane marker GFP‐Spo2051-91 was visualized following Cdc14 induction (n = 100).",
    "ncbi_link": "Cdc14: 850585"
  },
  {
    "caption": "A Phospho‐peptide abundance during Cdc14‐induced mitotic exit. Examples of phospho‐peptides that disappear with early (red), intermediate (orange) and late (green) timing or that remain stable (black) are shown. This color coding is used throughout all panels of this figure.B Numbers of unique peptides and corresponding proteins that do or do not contain a minimal Cdk consensus motif are shown, categorized according to timing of disappearance as described in (A).C Protein stability data for proteins corresponding to disappearing phospho‐peptides (blue) and for all other proteins (black).D The fractions of peptides that contain a minimal Cdk consensus motif ([S/T]‐P) within the timing categories shown in (B) were calculated. The ratio and P‐value of enrichment of each category relative to the combined stable/rest category (gray) are shown.E Similar to (D), the enrichment for reported physical Cdc14 interactors is assessed within [S/T]‐P‐containing phospho‐peptides.F Peptides that contain the indicated Cdk consensus sequence motifs and that have disappeared over time are represented as a fraction of all phospho‐peptides containing that motif.",
    "ncbi_link": "Cdk: 
Cdc14: 850585"
  },
  {
    "caption": "G Unique phospho‐peptides of Spa2, as an example, are categorized based on their dephosphorylation timing (graph). Enrichment of clustered timing for all proteins covered by phospho‐peptides was compared to random for Cdk or non‐Cdk consensus site‐containing peptides (table). Fisher's exact tests were used to determine significance.",
    "ncbi_link": "Cdk: "
  },
  {
    "caption": "B Western blot analysis of cells expressing conditional Clb2m (+) or Clb2mΔCdk (Δ) fusions to the indicated proteins, before (−) and 5 h after (+) β‐estradiol treatment. Tub1 served as a loading control. c, control cells.",
    "ncbi_link": "Cdk: 
Clb2: 856236"
  },
  {
    "caption": "C FACS analysis of DNA content after conditional Clb2m or Clb2mΔCdk fusion to the indicated proteins. Quantification of the fraction of cells with > 2C DNA content is shown in the bar graph for two independent biological replicates, with red dots representing individual and bars representing average values. Bnr1 fusions were included as controls for cytokinetic defects. Student's t‐test was applied to compare matched Clb2m versus Clb2mΔCdk fusion strains. ‐P > 0.05; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.",
    "ncbi_link": "Cdk: 
Clb2: 856236"
  },
  {
    "caption": "A Genes corresponding to the indicated proteins were replaced by wild‐type (wt) or Cdk phospho‐site mutant (xA) sequences and then conditionally fused to Clb2m or Clb2mΔCdk. Cytokinetic defects were scored by FACS analysis of DNA content as in Fig C. The individual values from two independent clones (red dots) as well as their average (bars) are shown. Student's t‐test was applied to compare matched wt and xA strains. c, control cells.",
    "ncbi_link": "Cdk: 
Clb2: 856236"
  },
  {
    "caption": "B Inn1‐Clb2m, Inn1‐Clb2mΔCdk and control cells before Clb2m fusion were arrested in G1 using α‐factor, released and harvested 90-100 min later at the time of cytokinesis. Indirect immunofluorescence microscopy was used to determine Inn1bud neck staining and the spindle status. Representative images of full spindles and partially and fully disassembled spindles are shown. nr, non‐recombined cells. Scale bars, 5 μm.",
    "ncbi_link": "Cdk: 
Clb2: 856236
Inn1: 855570"
  },
  {
    "caption": "C The time from anaphase onset until the GFP appearance of Inn1 was determined by filming synchronized Inn1‐Clb2m‐GFP and Inn1‐Clb2mΔCdk‐GFP cells containing Spc42‐YFP‐labeled spindle pole bodies. Error bars represent SD.",
    "ncbi_link": "Cdk: 
Clb2: 856236
Inn1: 855570"
  },
  {
    "caption": "D As in (C), now the persistence of a full actomyosin ring was measured in cells expressing Inn1‐Clb2m, Inn1‐Clb2mΔCdk or their respective non‐phosphorylatable mutants together with Myo1‐GFP and Spc42‐YFP. Error bars represent SD.",
    "ncbi_link": "Cdk: 
Clb2: 856236
Inn1: 855570"
  },
  {
    "caption": "E Montage of medial view projections of actomyosin rings in Inn1‐Clb2m and Inn1‐Clb2mΔCdk cells. Frames are shown in 2‐min intervals.F Actomyosin ring contraction phenotypes from at least 21 cells filmed as in (E) were blindly scored as having a normal (\"constriction\") or aberrant (\"disintegration\") cytokinetic phenotype.",
    "ncbi_link": "Cdk: 
Clb2: 856236
Inn1: 855570"
  },
  {
    "caption": "G Cytokinetic defect and cell viability of Inn1‐Clb2m or Inn1‐Clb2mΔCdk cells in the absence or presence of Chs2V377I. In the bar graph, red dots represent values of duplicate biological replicates with bars representing the average. Significance is calculated using Student's t‐test. 10‐fold spot dilution assays are represented, together with the Western blotting analysis for Inn1 before and after its fusion to Clb2m. Tub1 served as a loading control.",
    "ncbi_link": "Cdk: 
Chs2: 852326
Clb2: 856236
Inn1: 855570"
  },
  {
    "caption": "(B) Quantification of the co-localization of WT HOIP or HOIP mutants and Htt-Q97 aggregates. Data are displayed as mean ± SD and were analyzed by Mann-Whitney U-test, n = 3. Data information: *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "HOIP: 55072"
  },
  {
    "caption": "(C) Htt-Q97-GFP (green) was co-expressed with HA-tagged WT or HOIP mutants (red) in SH-SY5Y cells and analyzed by immunocytochemistry using an antibody against HA. DAPI (blue). Scale bar, 10 µm.",
    "ncbi_link": "HOIP: 55072"
  },
  {
    "caption": "(D) Recruitment of HOIP to Htt-Q97 is decreased in p97/VCP-deficient cells. p97/VCP-deficient SH-SY5Y cells co-expressing Htt-Q97 and HA-HOIP were reconstituted with either WT VCP or VCP∆PIM and analyzed by immunocytochemistry. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9. Data information: *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "p97/VCP: 7415
VCP: 7415"
  },
  {
    "caption": "(E) Recruitment of p97/VCP to Htt-Q97 is decreased in HOIP KO cells. WT HAP1 cells (control) or HOIP KO HAP1 cells reconstituted with either WT HOIP or HOIP∆PUB were analyzed by immunocytochemistry. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Bonferroni Multiple Comparison Test, n = 5. Data information: *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "HAP1: 9001
HOIP: 55072"
  },
  {
    "caption": "(F) The interaction of soluble Htt-Q60 with p97/VCP is dependent on HOIP. WT HAP1 cells or HOIP KO HAP1 cells were transfected with Htt-Q60-HA. 48 h after transfection cells were lysed with 1% Triton X-100, followed by an immunoprecipitation of Htt-Q60 via the HA tag. Immunopurified proteins were detected by Western blotting using an anti-VCP and anti-HOIP antibody.",
    "ncbi_link": "HA: 
HAP1: 9001
HOIP: 55072"
  },
  {
    "caption": "(A) Increased expression of HOIP decreases nuclear phospho-c-Jun in primary neurons. Primary mouse hippocampal neurons expressing Htt-Q25 or Htt-Q97 +/- HOIP were analyzed by immunocytochemistry using an antibody against phospho-c-Jun. Data are displayed as mean ± SD and were analyzed by 2 independent Mann-Whitney U-tests, n = 3. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "HOIP: 268749"
  },
  {
    "caption": "(B) Htt-Q97-induced toxicity is increased in cells silenced for HOIP. SH-SY5Y cells transiently transfected with Htt-Q25 or Htt-Q97 and either control siRNA (CO) or HOIP siRNA were analyzed by immunocytochemistry using an antibody against phospho-c-Jun. For rescue experiments, HOIP was co-expressed 24 h after silencing. Quantification of Htt-expressing cells with nuclear phospho-c-Jun is based on Student's t test from 3 independent experiments. Data are displayed as mean ± SD unless otherwise stated. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
HOIP: 55072"
  },
  {
    "caption": "OTULIN silencing decreases the toxicity of Htt-Q97. SH-SY5Y cells transiently transfected with either control siRNA (CO) or OTULIN siRNA and Htt-Q25 or Htt-Q97 were analyzed by immunocytochemistry using antibodies against phospho-c-Jun (C) Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9-11. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
OTULIN: 90268"
  },
  {
    "caption": "OTULIN silencing decreases the toxicity of Htt-Q97. SH-SY5Y cells transiently transfected with either control siRNA (CO) or OTULIN siRNA and Htt-Q25 or Htt-Q97 were analyzed by immunocytochemistry using antibodies against cleaved caspase-3 (D). Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9-11. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
OTULIN: 90268"
  },
  {
    "caption": "(E) The protective effect of HOIP is independent of NF-κB signaling. SH-SY5Y cells transiently transfected with Htt-Q97-GFP and either control vector (CO) or HOIP ± the NF-κB super-repressor IκB-2S/A were analyzed by immunocytochemistry using an antibody against phospho-c-Jun. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "GFP: 
Htt: 3064
IκB: 3551
HOIP: 55072"
  },
  {
    "caption": "(F) SDS-soluble Htt-polyQ species are modified by linear ubiquitin chains. HEK293T cells were co-transfected with Htt-Q60-GFP (as a control for specific immunoprecipitation of HA-tagged Htt-Q60), Htt-Q60-HA or Htt-Q60-3R (3 lysine residues replaced by arginines) and the plasmids indicated. Cells were lysed under denaturing conditions (1% SDS), followed by immunoprecipitation of Htt via the HA tag (1% Triton X-100, 0.1% SDS). Immunopurified proteins were detected by Western blotting using the M1 ubiquitin-specific antibody 1E3 and anti-HA.",
    "ncbi_link": "GFP: 
HA: 
Htt: 3064"
  },
  {
    "caption": "(G) Silencing of OTULIN increases linear ubiquitination of Htt-Q97. A linear ubiquitination assay was performed as described in (F) with HEK293T cells transfected with Htt-Q97-HA and control siRNA or OTULIN siRNA.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "(A) The interaction between Htt-Q97 and Sp1 is decreased by linear ubiquitination. HEK293T cells were co-transfected with Htt-Q97-HA and the siRNAs indicated. Htt-Q97-GFP was transfected as a control for specific immunoprecipitation of HA-Htt-Q97. Nuclear (left panel) and cytosolic fractions (middle panel) were subjected to an anti-HA immunoprecipitation followed by Western blotting using an anti-Sp1 antibody. Right panel: Input controls (whole cell lysates).",
    "ncbi_link": "GFP: 
HA: 
Htt: 3064"
  },
  {
    "caption": "(C, D) Impairment of Sp1-mediated transcription by Htt-Q97 is modified by HOIP. (C) Shown is the relative luciferase activity in HEK293T cells expressing Htt-Q97-HA, a Sp1 luciferase reporter construct and HOIP cDNA. Data are displayed as mean ± SD and were analyzed by Kruskal-Wallis test followed by Dunn's Multiple Comparison Test, n = 9-11. (D) Shown is the relative luciferase activity in HEK293T cells expressing Htt-Q97-HA, a Sp1 luciferase reporter construct and HOIP siRNA. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "HA: 
Htt: 3064
HOIP: 55072
Sp1: 6667"
  },
  {
    "caption": "(E) Sp1 silencing decreases HOIP and SHARPIN protein expression. SH-SY5Y cells were transfected with control or Sp1-specific siRNAs and analyzed for protein expression 2 days after transfection by immunoblotting (left panel). Quantification of normalized Sp1, HOIP and SHARPIN protein expression levels (right panel). Data are displayed as mean ± SEM with n=5 from unpaired two-tailed Student's t-tests. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "Sp1: 6667"
  },
  {
    "caption": "(F) HOIP-, HOIL-1L- and SHARPIN-specific mRNA is decreased in R6/2 striatum. Quantification of mRNA from the striatum of 9-12 weeks old R6/2 mice and non-transgenic littermates. Data are displayed as mean ± SD with n = 6-9 biological replicates from unpaired two-tailed Student's t-tests. *p ≤ 0.05, ***p ≤ 0.001.",
    "ncbi_link": "HOIL-1L: 24105
HOIP: 268749
SHARPIN: 106025"
  },
  {
    "caption": "(D) SDS-soluble SOD G85R and TDP-43 Q331K species are modified by linear ubiquitin chains. HEK293T cells were co-transfected with disease-associated proteins and either the plasmids indicated or with control siRNA or OTULIN siRNA. 48 h after transfection cells were lysed under denaturing conditions (1% SDS), followed by immunoprecipitation of SOD G85R and TDP-43 Q331K via the HA tag (1% Triton X-100, 0.1% SDS). Immunopurified proteins were detected by Western blotting using the M1 ubiquitin-specific antibody 1E3.",
    "ncbi_link": "OTULIN: 90268
SOD: 6647
TDP-43: 23435"
  },
  {
    "caption": "(A) Linear ubiquitination reduces the fraction of cells with Htt-Q97 aggregates. SH-SY5Y cells were transfected with Htt-Q97 and either control siRNA, HOIP siRNA or OTULIN siRNA. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 9. Expression levels of HOIP and OTULIN were analyzed by Western blotting. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
OTULIN: 90268
HOIP: 55072"
  },
  {
    "caption": "(B) Linear ubiquitination reduces the fraction of cells with Htt-Q97 aggregates. SH-SY5Y cells were transfected with Htt-Q97 and either WT HOIP or the catalytically inactive HOIP mutant C885A. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey s Multiple Comparison Test, n = 5. Expression levels of WT and mutant HOIP and OTULIN were analyzed by Western blotting. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
HOIP: 55072"
  },
  {
    "caption": "(C) The effect of HOIP on Htt-Q97 aggregation is independent of NF-κB signaling. SH-SY5Y cells transiently transfected with Htt-Q97 and either control vector (CO) or WT HOIP plus the NF-κB super-repressor IκB-2S/A were analyzed by immunocytochemistry. Data are mean ± SD with n=5 from an unpaired two-tailed Student's t-test. Expression levels of WT HOIP and IκB-2S/A were analyzed by Western blotting. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "Htt: 3064
IκB: 3551
HOIP: 55072"
  },
  {
    "caption": "(D) Catalytically active HOIP decreases the number of cells with Htt-Q97 aggregates independently of autophagy. WT and ATG5 KO MEFs were transiently transfected with Htt-Q97-GFP and either control vector (CO), HOIP or HOIP C885A. Cells were treated 24 h after transfection with the proteasomal inhibitor MG132 (1 µM, 16 h). Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Tukey's Multiple Comparison Test, n = 7. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "GFP: 
ATG5: 11793
Htt: 15194
HOIP: 268749"
  },
  {
    "caption": "(E) Linear ubiquitination reduces the fraction of cells with TDP-43 Q331K aggregates. SH-SY5Y cells were transfected with TDP-43 Q331K and either control siRNA, HOIP siRNA or OTULIN siRNA. Data are displayed as mean ± SD and were analyzed by Kruskal-Wallis test, followed by Dunn's Multiple Comparison Test, n = 7. Expression levels of HOIP and OTULIN were analyzed by Western blotting. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "OTULIN: 90268
HOIP: 55072
TDP-43: 23435"
  },
  {
    "caption": "(F) Catalytically active HOIP decreases the number of cells with TDP-43 aggregates dependent on proteasomal degradation. SH-SY5Y cells were transfected with TDP-43 Q331K and either control vector (CO), HOIP or HOIP C885A. Cells were treated 48 h after transfection with the proteasomal inhibitor MG132 (1 µM) or the p97/VCP inhibitor NSM-873 (1 µM) for 3 h. Data are displayed as mean ± SD and were analyzed by one-way ANOVA followed by Dunnett's Multiple Comparison Test, n = 5. Data information: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.",
    "ncbi_link": "HOIP: 55072
TDP-43: 23435"
  },
  {
    "caption": "(C) Interaction analysis between hCAP-G and hCAP-H. Bacterial cell lysates co-expressing hCAP-G (residues 1-478, 554-900) and hCAP-H (residues 394-515), either wild type (WT; lanes 2, 10 and 13), 3Q (F463Q, F469Q and F473Q; lane 3), 5Q (F463Q, F469Q, F473Q, F501Q and Y503Q; lane 4), 3A (F463A, F469A and F473A; lane 5), 5A (F463A, F469A, F473A, F501A and Y503A; lane 6) or 2A (F501A and Y503A; lane 11), or a C-terminal deletion mutant (506-514 residues were deleted from 394-515; lane 14) were applied to Ni-NTA agarose resin, and the bound fraction was analyzed by SDS-PAGE. Alternatively, a cell lysate co-expressing mutant hCAP-G (D647K) and wild-type hCAP-H was examined (lane 7). The uninduced cell lysate was also used as a negative control (lane 9).",
    "ncbi_link": "hCAP-G: 64151
hCAP-H: 23397"
  },
  {
    "caption": "(A) Expression of condensin I subunits in insect cells. The wild-type (WT) or IV-5Q mutant CAP-H subunit was co-expressed with the other four subunits (GST-SMC4, SMC2, CAP-D2 and CAP-G) in insect cells. Cell lysates were prepared and subjected to SDS-PAGE, followed by immunoblotting with a mixture of antibodies against SMC2 and SMC4 (left panel) or against CAP-D2, -G, and -H (right panel).",
    "ncbi_link": "CAP-H: 23397"
  },
  {
    "caption": "(A) Purification of hCAP-G and hCAP-G-H subcomplexes: wild type (WT), CAP-G K60D/R848E double mutant (K60D/R848E) and CAP-G R168E mutant (R168E). Purified protein samples were subjected to SDS-PAGE and analyzed by CBB staining.",
    "ncbi_link": "CAP-G: 64151"
  },
  {
    "caption": "(B) Double-stranded DNA (dsDNA) and single-stranded DNA binding assay of the hCAP-G. 30-bp dsDNA was incubated with no protein (lanes 1) or increasing amounts of WT hCAP-G (WT; lanes 2-4). 30-mer ssDNA was incubated with no protein (lanes 5) or increasing amounts of WT hCAP-G (WT; lanes 6-8).",
    "ncbi_link": "hCAP-G: 64151"
  },
  {
    "caption": "(C) The dsDNA binding assay for the hCAP-G-H subcomplexes. 30-bp dsDNA was incubated with no protein (lanes 1, 5 and 9), increasing amounts of WT hCAP-G-H subcomplex (WT; lanes 2-4), CAP-G K60D/R848E double mutant (K60D/R848E; lanes 6-8) or CAP-G R168E mutant (R168E; lanes 10-12).",
    "ncbi_link": "CAP-G: 64151
hCAP-G: 64151"
  },
  {
    "caption": "Kaplan-Meier curves for overall survival (OS) in lung adenocarcinoma TCGA_LUAD (RASSF1 mRNA high/low cutoff FKPM 5.85) and squamous cell carcinoma patients TCGA_LUSC (RASSF1 mRNA high/low cutoff FKPM 6.52). Significance derived from log-rank test.",
    "ncbi_link": "RASSF1: 11186"
  },
  {
    "caption": "Western blot with indicated antibodies of isogenic H1299 cells stably transfected with either empty vector pcDNA3 (H1299control) or RASSF1A (H1299RASSF1A). Bottom: cell proliferation resazurin assay. (n=2). Error bars represent mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Size of lung primary tumours measured at day 30 after lung orthotopic injection either with H1299control (n=14 mice per group; experimental groups of 6 and 8 different shading within the groups represents two independent experiments) or with H1299RASSF1A cells stably re-expressing RASSF1A, (n=12 mice per group; experimental groups of 6 and 6). The size of primary tumours was measured by MRI software ITK-SNAP. Statistical significance via 2-tailed Student's t-test. Error bars represent mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Visual assessment quantification of metastatic events on the ipsilateral (left) and or contralateral (right) lungs, generated by H1299control or H1299RASSF1A at day 30. Result was calculated from 2 independent in vivo experiments Graph shows significant decreasing of metastases when lungs were injected with H1299RASSF1A. Statistical significance via 2-tailed Student's t-test. Error bars represent mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Mass-spectrometry analysis of proteins purified from extracellular matrix isolated from H1299control and H1299RASSF1A lung adenocarcinoma cell lines with summary of results. Only proteins identified with two or more peptides were taken into consideration. The resulting list of proteins was restricted to ECM proteins (n=3).",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative images of H&E and IHC staining for P4HA2, and quantification (bars) of two independent regions of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours. Scale bars 100µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Western blot indicating levels of Collagen I in H1299control and H1299RASSF1A cells.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Western blot indicating levels of Collagen I in H1299control cells in the presence of (4μM) prolylhydroxylase inhibitor (DPCA), siRNA against P4HA2 or combination.",
    "ncbi_link": "P4HA2: 8974"
  },
  {
    "caption": "Quantification of immunofluorescence staining of Collagen I in H1299control cells in the presence of (4μM) prolylhydroxylase inhibitor (DPCA), siRNA against P4HA2 or combination. H1299RASSF1A cell line was used as negative control for comparison. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "P4HA2: 8974
RASSF1A: 11186"
  },
  {
    "caption": "Immunofluorescence staining for Collagen I and P4HA2 and quantification (right graph) in HOP92 cells after siRNA against RASSF1A. Scale bars 20µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Western blot analyses in HOP92 cells showing increased expression of collagen I after siRNA against RASSF1A.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Immunofluorescence staining for Collagen I and P4HA2 and quantification (right graph) in HeLa cells after siRNA against RASSF1A. Scale bars 20µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test (2-tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Invasion of H1299control and H1299RASSF1A cells through three-dimensional collagen matrix coated inserts, over 24 hours (n=3). Scale bars 100µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative images and quantification of H1299 cells treated with siNT, siRNA against P4HA2 or in the presence of the prolylhydroxylase inhibitor DPCA (4μM), and allowed to invade for 24 hours through a three-dimensional Matrigel matrix Boyden chamber. Scale bars 100µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "P4HA2: 8974"
  },
  {
    "caption": "Representative images and quantification of HOP92 cells stably transfected with shcontrol or shRASSF1A and allowed to invade for 24 hours through a three-dimensional Matrigel matrix Boyden chamber. Scale bars 100µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "3D collagen contraction assay: 5x105/ml cells were embedded into collagen rat tail I matrix (2mg/ml) and analysed after 4 days. White circles indicates diameter of gel plugs at time 0. Representative bright-field images (bottom) with quantification, showing the effect of H1299RASSF1A or H1299control cells on collagen gel remodelling and after cells pre-treatment with siRNA against P4HA2, 4μM DPCA or combination as indicated. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "P4HA2: 8974
RASSF1A: 11186"
  },
  {
    "caption": "Upper image: Cartoon of hanging drops method for spheroids formation and embedding collagen rat tail I matrix (2mg/ml). Bottom: Representative immunofluorescence images of YAP distribution and its nuclear quantification (right bars) by Pearson's coefficient for correlation of YAP and DAPI co-staining in H1299control and H1299RASSF1A 3D spheroids grown in 3D collagen matrix (2mg/ml). Scale bars 10µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Relative mRNA expression levels of P4HA2 and YAP target genes CYR61 and CTGF in H1299control cells in presence of siNT or siRNA targeting YAP1. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
P4HA2: 8974
YAP1: 10413"
  },
  {
    "caption": "Representative immunofluorescence images of YAP distribution (right) and its nuclear quantification by Pearson's coefficient for correlation (left) of YAP and DAPI co-staining in H1299control and H1299RASSF1A plated on extracted ECM from H1299control or H1299RASSF1A cells with or without treatment with siP4HA2 or 4μM DPCA. (Correlation, Pearson's coefficient). (n=3, 300 cells per experiment) Scale bars 10µm. Data information: Unless otherwise indicated all statistical analyses were performed using Student's t-test 2-(tailed) of n=3 experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "P4HA2: 8974
RASSF1A: 11186"
  },
  {
    "caption": "Bar graph representing quantification of stiffness measured by atomic force microscopy (Young modulus) of ECM area generated by H1299control or H1299RASSAF1A cells in vitro. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSAF1A: 11186"
  },
  {
    "caption": "Representative atomic force microscopy (AFM) images showing organization of extracellular matrix generated by H1299control and H1299RASSF1A cells in 3D collagen matrices (2mg/ml).",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Bar graph representing quantification of stiffness by atomic force microscopy (Young modulus) in of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours on day 30. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative topographic images of stiffness map of H1299control and H1299RASSF1A lung primary tumours provided by AFM.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "AFM images of ECM fibre organization within primary lung tumours generated by H1299control and H1299RASSF1A cells on day 30.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Second harmonic generation (SHG) representative Images and Quantification (bars) showing deposition and organization of collagen fibres produced by H1299control and H1299RASSF1A spheroids embedded in collagen I matrix (2mg/ml), treated with siNT, siRNA against P4HA2 or 4μM DPCA to restrict P4HA2 activity. Red arrowheads show highly organized, long collagen fibres. Scale bars 20µm. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "P4HA2: 8974
RASSF1A: 11186"
  },
  {
    "caption": "Representative H&E and quantification (bars) of picrosirius red staining of two independent regions of n=5 H1299control and n=3 H1299RASSF1A primary lung tumours. Scale bars 100µm, zoom 20µm. Data information: All statistical analyses were performed using Student's t-test (2-tailed) of n=3 for in vitro experiments and error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative immunofluorescence images show merge of NANOG (green), DAPI (blue) distribution in H1299control and H1299RASSF1A cells cultured on 2D glass. Scale bars 10µm. Right: Quantification of nuclear co-localization (n=200cells/experiment) is represented by Pearson's coefficient.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative immunofluorescence images of CD133 in H1299control and H1299RASSF1A cells grown on 3D collagen wells with defined stiffness. Scale bars 10µm. Bottom: Quantification of n=200 cells/experiment. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative images of H&E and immunohistochemical staining for NANOG and YAP1 in primary lung tumours, (day 17). Scale bars 100µm. Right: Graph bars represent quantification of NANOG and YAP1 staining based on strong (3+, 2+) nuclear intensity (%) for at least 2 independent regions of n=4 H1299control and n=2 H1299RASSF1A primary tumours at day 17. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Relative mRNA expression levels of NANOG, OCT4 and SOX2 in H1299control and H1299RASSF1A lung adenocarcinoma cells. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "ncbi_link": "NANOG: 79923
OCT4: 5460
RASSF1A: 11186
SOX2: 6657"
  },
  {
    "caption": "Representative immunofluorescence images of NANOG and YAP in the presence of siNT or siYAP in H1299control and H1299RASSF1A cells embedded and grown in three-dimensional collagen matrix (2mg/ml). Scale bars 10µm.",
    "ncbi_link": "RASSF1A: 11186
YAP: 10413"
  },
  {
    "caption": "Western blots of H1299control and H1299RASSF1A lysates for NANOG, SOX2 and OCT4 in the presence of siNT or siYAP.",
    "ncbi_link": "RASSF1A: 11186
YAP: 10413"
  },
  {
    "caption": "Relative H1299control mRNA expression levels NANOG, OCT4 and SOX2 in H1299control cells in the presence of siNT or siYAP. Data information: Statistical significance was determined by Student's t-test (2-tailed) of n=3 experiments unless otherwise stated. Error bars represent the mean ± S.E.M.",
    "ncbi_link": "NANOG: 79923
OCT4: 5460
SOX2: 6657
YAP: 10413"
  },
  {
    "caption": "Representative immunofluorescence images of H1299control and H1299RASSF1A spheroids embedded and grown in collagen matrix (2mg/ml) and stained for NANOG (Green) and YAP (Red) with or without 4μM DPCA. Scale bars 10µm.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Western blots of H1299control lysates for NANOG, SOX2 and OCT4 in the presence of siNT, siP4HA2 or 4μM DPCA.",
    "ncbi_link": "P4HA2: 8974"
  },
  {
    "caption": "Western blot analyses of expression levels of TTF-1 and Mucin 5B in H1299control and H1299RASSF1A cells with band intensity quantification ratio determine by ImageJ analyser.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Representative images of H&E and immunohistochemical staining for lung differentiation markers TTF-1 and Mucin 5B for at least 2 independent regions of n=4 H1299control and n=2 H1299RASSF1A primary tumours at day 17 with quantification (right) of TTF-1 based on nuclear intensity. Scale bars 100µm. Statistical significance was determined by Student's t-test (2-tailed). Error bars represent the mean ± S.E.M",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "Bright field images of H1299control and H1299RASSF1A spheroid differentiation on Matrigel matrix after 24 hours when 3D spheroids were seeded on three-dimensional substrate. Scale bars 200µm.",
    "ncbi_link": "RASSF1A: 11186"
  },
  {
    "caption": "HeLa  cells co-transfected with EMTB-CFP-FRB  and YFP-FKBP  were treated with 100 nM rapamycin  (Rapa). Addition of rapamycin  rapidly translocated YFP-FKBP  onto EMTB-CFP-FRB-labeled microtubules  and increased the FRET  signal. The scale for the FRET/CFP  intensity ratio is shown. Scale bar, 10 μm. The normalized intensity of FRET/CFP  in cells before and after rapamycin  (blue) and 0.1% DMSO  (control; red) treatment. n = 6 and 10 cells in the rapamycin  and DMSO  groups, respectively, from three independent experiments. Data are shown as the mean ± S.E.M.",
    "ncbi_link": "CFP: 
YFP: 
FKBP: 2280
EMTB: 9053
FRB: 2475"
  },
  {
    "caption": "HeLa  cells co-transfected with the indicated constructs were treated with nocodazole  (Noc, 3.3 µM; left) or rapamycin  (Rapa, 100 nM; right) for 0, 30, and 60 min. Transfected cells were then fixed and labeled with anti-acetylated tubulin  (red). Dotted lines indicate the boundary of transfected cells. Scale bars, 10 μm. The intensity of acetylated tubulin  in cells transfected with EMTB-CFP-FRB  (orange) or cotransfected with EMTB-CFP-FRB and dNSpastin3Q-YFP-FKBP  (blue) after addition of nocodazole  (Noc, 3.3 µM) or rapamycin  (Rapa, 100 nM) for the indicated times. n = 123 and 81 cells in the nocodazole  and dNSpastin3Q groups, respectively, from three independent experiments. Data are shown as the mean ± S.E.M. Student's t-tests were performed, with p-values indicated.",
    "ncbi_link": "YFP: 
FKBP: 2280
EMTB: 9053
FRB: 2475
Spastin: 50850"
  },
  {
    "caption": "COS7  cells transfected with TagRFP-FRB-A1AY1  (red) were labeled by anti-α-tubulin antibody (green; upper panel), anti-tyrosinated tubulin  antibody (green; middle panel), or anti-detyrosinated tubulin  antibody (green; lower panel), respectively. Scale bar, 10 µm. The intensity profiles of TagRFP-FRB-A1AY1   (red) and tubulin  with the indicated PTMs   (green) along dotted lines drawn in (A). The Pearson's correlation coefficients for TagRFP-FRB-A1AY1  and indicated tubulin  (tub) subtypes were calculated, and data are shown as the mean ± S.E.M. n = 16, 13, and 15 cells from left to right, respectively; three independent experiments.",
    "ncbi_link": "A1AY1: 
RFP: 
FRB: 2475"
  },
  {
    "caption": "COS7  cells co-transfected with TagRFP-FRB-A1AY1   (red) and TagCFP-FKBP   (green) were treated with rapamycin  (100 nM). The addition of rapamycin  rapidly recruits TagCFP-FKBP  from cytosol  onto A1AY1-labeled microtubules  (arrows). Scale bar, 10 µm. The normalized intensity of TagCFP-FKBP  at A1AY1-labeled microtubules  upon rapamycin  treatments. n=7 cells from three independent experiments. Data are shown as the mean ± S.E.M.",
    "ncbi_link": "A1AY1: 
CFP: 
RFP: 
FKBP: 2280
FRB: 2475"
  },
  {
    "caption": "COS7  cells co-transfected with TagRFP-FRB-A1AY1   (red) and dNSpastin3Q-TagCFP-FKBP  (cyan) were treated with 0.1% DMSO  or rapamycin  (100 nM) for 1 hr and followed by immunostaining  with anti-tyrosinated tubulin  antibody (green). Dotted lines highlight the transfected cells. Scale bar, 20 μm. The normalized intensity of tyrosinated microtubules  in TagRFP-FRB-A1AY1  and dNSpastin3Q-TagCFP-FKBP  co-transfected cells upon 0.1% DMSO  or rapamycin  treatment for 1 hr. n=31 and 26 cells in DMSO  and rapamycin  treated groups, respectively, from three independent experiments. Data (blue) represent as mean ± S.E.M. Student's t-tests were performed with p values indicated.",
    "ncbi_link": "A1AY1: 
CFP: 
RFP: 
FKBP: 2280
FRB: 2475
Spastin: 50850"
  },
  {
    "caption": "COS7  cells co-transfected with EMTB-YFP-CIBN  and mCh-Cry2  (red) were incubated with SPY650-tubulin    (SPY650-tub) to visualize microtubules. The cells were illuminated by  blue light within a specified region (indicated by the dotted circle) for the indicated time period. Scale bar, 10 μm. The normalized intensity of mCh-Cry2  at microtubules  in illuminated regions (red) and non-illuminated regions (green). n = 6 cells from three independent experiments. Data are shown as the mean ± S.E.M.",
    "ncbi_link": "mCh: 
YFP: 
CIBN: 829604
Cry2: 839529
EMTB: 9053"
  },
  {
    "caption": "COS7  cells co-transfected with EMTB-YFP-CIBN  and dNSpastin3Q-mCh-Cry2  were incubated with SPY650-tubulin   to visualize microtubules. The cells were illuminated by  blue light as in (A). Scale bar, 10 μm. The normalized intensity of dNSpastin3Q-mCh-Cry2  and mCh-Cry2  at microtubules  and the normalized area of SPY650-tubulin   in illuminated regions and non-illuminated regions. n = 6 and 6 cells in dNSpastin3Q-mCh-Cry2  and mCh-Cry2  groups, respectively, from three independent experiments. Data are shown as the mean ± S.E.M.",
    "ncbi_link": "mCh: 
YFP: 
CIBN: 829604
Cry2: 839529
EMTB: 9053
Spastin: 50850"
  },
  {
    "caption": "E-F. COS7  cells co-transfected with EMTB-CFP-FRB, dNSpastin3Q-mCh-FKBP, and Tom20-Neon   were treated with rapamycin  (100 nM) for acute microtubule disruption. The morphology  of mitochondria  at different levels of microtubule  disruption is shown. Scale bar, 10 µm. The ratio of the long axis to the short axis of each mitochondrion  and microtubule filament area was determined. n= 4 different cells, three independent experiments. Data are shown as the mean ± S.E.M. Data information: Student's t-tests were performed with p values indicated.",
    "ncbi_link": "CFP: 
mCh: 
Neon: 
FKBP: 2280
EMTB: 9053
FRB: 2475
Spastin: 50850
Tom20: 781575"
  },
  {
    "caption": "G-H. The normalized intensity of MitoTracker Red  in non-transfected cells (Mock) or cells co-transfected with EMTB-CFRP-FRB  and dNSpastin3Q-YFP-FKBP  or dNSpastin3QED-YFP-FKBP  after rapamycin  (Rapa, 100 nM) treatment for the indicated time. Scale bar, 10 µm. n = 41, 6, and 18 cells from three independent experiments. Data are shown as the mean ± S.E.M. Data information: Student's t-tests were performed with p values indicated.",
    "ncbi_link": "CFRP: 
YFP: 
FKBP: 2280
EMTB: 9053
FRB: 2475
Spastin: 50850"
  },
  {
    "caption": "Cell number  in the bone marrow of wild-type and Hdac6  knockout mice  (n = 12-13 mice  per group). Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (Student's t test).",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "Flow cytometry  profiles for the LK  and LSK  subsets in wild-type and Hdac6  knockout mice.",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "Frequency of the LK subset in wild-type and Hdac6  knockout mice  (n = 12-13 mice  per group). Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (Student's t test).",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "L. number of the LSK subset in wild-type and Hdac6  knockout mice  (n = 12-13 mice  per group). Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (Student's t test).",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "Representative images of colonies formed by bone marrow cells  from wild-type and Hdac6  knockout mice. Scale bar, 200 µm. Number of colonies formed by bone marrow cells from wild-type and Hdac6  knockout mice  (n = 10 mice  per group). Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (Student's t test).",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "J. Immunoprecipitation  and immunoblotting  with various truncated mutants of HA-HDAC6  to identify the domains that mediate its interaction  with GFP-IDH1. K. Immunoprecipitation  and immunoblotting  with various truncated mutants of GFP-IDH1  to identify the domains that mediate its interaction  with HA-HDAC6.",
    "ncbi_link": "GFP: 
HA: 
HDAC6: 10013
IDH1: 3417"
  },
  {
    "caption": "Immunoprecipitation  and immunoblotting  showing the level of IDH1 acetylation  in HEK293T  cells transfected with wild-type GFP-IDH1  or various mutants, These cells were treated with the HDAC6  inhibitor, tubacin",
    "ncbi_link": "GFP: 
IDH1: 3417"
  },
  {
    "caption": "Immunoprecipitation  and immunoblotting  showing the level of IDH1 acetylation  in HEK293T  cells transfected with wild-type GFP-IDH1  or various mutants, These cells were transfected with the HDAC6  siRNA",
    "ncbi_link": "GFP: 
HDAC6: 10013
IDH1: 3417"
  },
  {
    "caption": "Immunoblotting  (E) in HEK293T  cells transfected with plasmids expressing GFP, GFP-IDH1, GFP-IDH1  K233R, or GFP-IDH1  K233Q. In panel E, the black arrowhead indicates exogenous IDH1, while the white arrowhead marks endogenous IDH1.",
    "ncbi_link": "GFP: 
IDH1: 3417"
  },
  {
    "caption": "G-H. Immunoblotting  (G) and IDH1  activity analysis (H, n = 6-9 tests from three independent experiments) in HEK293T cells transfected with control or HDAC6  siRNAs and plasmids expressing GFP, GFP-IDH1, GFP-IDH1  K233R, or GFP-IDH1 K233Q. In panel G, the black arrowhead indicates exogenous IDH1, while the white arrowhead marks endogenous IDH1. Data information: All values are presented as mean ± SEM. **P < 0.01, ***P < 0.001, ****P < 0.0001 ANOVA test",
    "ncbi_link": "GFP: 
HDAC6: 10013
IDH1: 3417"
  },
  {
    "caption": "K. Representative images of the colony formation assay. Scale bar, 200 µm. L. Number of colonies formed by wild-type and Hdac6  knockout mice bone marrow cells treated or untreated with 10 µM GSK321  (n = 6 mice  per group). Data information: All values are presented as mean ± SEM. **P < 0.01, ***P < 0.001, ****P < 0.0001 ANOVA test",
    "ncbi_link": "Hdac6: 15185"
  },
  {
    "caption": "qPCR  showing that knockdown of HDAC6   significantly upregulates the expression of TET2   target genes with hyper-hydroxymethylation. Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (ANOVA test).",
    "ncbi_link": "HDAC6: 10013"
  },
  {
    "caption": "qPCR  showing that knockdown of HDAC6  significantly upregulates the expression of TET2  target genes with hyper-hydroxymethylation. qPCR  showing that treatment with 10 µM GSK321  inhibits the upregulation of the indicated genes in HDAC6-knockdown HEK293T  cells. Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (ANOVA test).",
    "ncbi_link": "HDAC6: 10013"
  },
  {
    "caption": "qPCR  showing that treatment with 10 µM GSK321  inhibits the upregulation of the indicated genes in HDAC6-knockdown HEK293T  cells. Data information: All values are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant (ANOVA test).",
    "ncbi_link": "HDAC6: 10013"
  },
  {
    "caption": "b. After 5 passages (p2, p3, p4 and p5) on VeroE6 cells, the mCherry reporter gene in ISA mCherry D614 supernatant medium was RT-PCR amplified and analysed using gel electrophoresis.",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "a: Dose response curve for the ISA D614 and for the mCherry D614 strains obtained by fluorescence or viral RNA measurement in VeroE6 cells from one representative experiment. Data are represented as mean ± SD (indicated by the error bars). Each experiment was performed in technical triplicates (N=3). b: Table of EC50 values obtained for the two different strains from two technical replicates. and their respective mean ± SD. c",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "(A, B and C)  Polyphenols TA , PGG and EGCG activate  rhpR-lux  in wild type but not rhpS  deletion Psph  strains. Data information: , * indicate significant differences between mock group and strains under the different test conditions. (Student's t test. n.s., not significant, *, P ≤ 0.05, **, P ≤ 0.01, and ***, P ≤ 0.001). Error bars represent standard deviations (n=3 biological replicates).",
    "ncbi_link": "lux: 
rhpR: 
rhpS: "
  },
  {
    "caption": "(E) Alanine-scanning mutagenesis of the RhpS sensor. RhpS containing a corresponding mutation was provided in the  rhpS deletion strain on a pHM1 vector. LUX activity was estimated in the absence (black frame) and presence  TA  (50-μM), PGG (100-μM) or EGCG (2-mM). Error bars represent standard deviations (n=3 biological replicates). Data information: , * indicate significant differences between mock group and strains under the different test conditions as indicated. (Student's t test. *, P ≤ 0.05, **, P ≤ 0.01, and ***, P ≤ 0.001).",
    "ncbi_link": "rhpS: 
RhpS: "
  },
  {
    "caption": "(C and D) The rhpS/PSPPH_3550/PSPPH_3736/PSPPH_5115 quadruple deletion strain restored the T3SS induction of  rhpS  deletion strain. The wild type, rhpS  deletion and quadruple deletion strains were cultured in MM (C) for 6 hours or  KB (D) to OD600=0.6. Transcripts of the indicated genes were determined by RT-qPCR. Data information: , * indicate significant differences between rhpS mutant and quadruple mutant. Error bars represent standard deviations (n=3 biological replicates). Student's t test. *, P ≤ 0.05, **, P ≤ 0.01, and ***, P ≤ 0.001.",
    "ncbi_link": "PSPPH_3550: 
PSPPH_3736: 
PSPPH_5115: 
rhpS: 
T3SS: 64442672"
  },
  {
    "caption": "(F) The quadruple mutant strain restored the pathogenicity of rhpS  deletion strain. Bacterial virulence levels were estimated by inoculating wild type, rhpS deletion and quadruple deletion strains onto host  bean plants. Disease symptoms were recorded 5 days after inoculation. The experiment was repeated three times.",
    "ncbi_link": "rhpS: "
  },
  {
    "caption": "(G) Leaf  disks (1 cm2) from (G) were removed 5 days after inoculation and diluted in sterile water to count bacterial CFUs. The experiment was repeated three times. Data information: , * indicate significant differences between  rhpS  mutant and quadruple mutant. Error bars represent standard deviations (n=3 biological replicates). Student's t test. *, P ≤ 0.05, **, P ≤ 0.01, and ***, P ≤ 0.001.",
    "ncbi_link": "rhpS: "
  },
  {
    "caption": "D, E Following heat shock and recovery for 4 h, mRNA levels in reporter cells treated with and without 10 mM metformin overnight were quantitated by qRT-PCR (mean ± SD, n = 3, Student's t-test, **P < 0.01, ***P < 0.001). β-actin was used as the internal control.",
    "ncbi_link": "β-actin: "
  },
  {
    "caption": "G Left panel, graphic depiction of the ELISA-based DNA binding assay. HSE: heat shock element. Right panel: Immediately following heat shock at 43°C for 30 min, nuclear proteins of the reporter cells treated with and without 10 mM metformin were extracted for assay (mean ± SD, n = 3, Student's t-test, **P < 0.01, ***P < 0.001). Experimental details are described in Materials and Methods.",
    "ncbi_link": "HSE: "
  },
  {
    "caption": "I HEK293T cells stably expressing a scramble or HSF1-targeting shRNA were treated with 10 mM metformin overnight and heat-shocked at 43°C for 30 min. Cells were fixed for PLA to detect HSF1-DNA interactions. Experimental details are described in Materials and Methods. Scale bars: 50 μm for low magnification and 10 μm for high magnification.",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "A-C Reporter cells were treated with and without 1 μM A-769662 for 3 h followed by heat shock at 43°C for 30 min and recovery at 37°C for 5 h. Hspa1a and Hspb1 mRNA levels were quantitated by qRT-PCR (mean ± SD, n = 3, Student's t-test, ***P < 0.001). ACC phosphorylation was detected by immunoblotting (C).",
    "ncbi_link": "Hspa1a: 193740
Hspb1: 15507"
  },
  {
    "caption": "D-F Primary MEFs were derived from Ampkα1fl/fl; Ampkα2fl/fl embryos and transduced with either adenoviral GFP or Cre to delete Ampkα1/2 in vitro. AMPKα levels were detected 4 days after transductions (D)",
    "ncbi_link": "Cre: 
GFP: 
Ampkα1: 105787
Ampkα2: 108079"
  },
  {
    "caption": "G Transcriptional activities of HSF1 were measured by a dual reporter system consisting of two plasmids: the HSF1-dependent reporter pHSE-SEAP, in which ideal HSEs drive the expression of secreted alkaline phosphatase (SEAP), and the control reporter pCMV-Gaussia Luc, in which a CMV promoter drives the expression of secreted Gaussia luciferase. In HEK293T cells, either LacZ or GST-AMPKα1CA plasmid was co-transfected with the two reporter plasmids. After 24 h, the transfected cells were heat-shocked at 44°C for 45 min. The culture supernatants were collected to measure SEAP and luciferase activities 24 h after heat shock. SEAP signals were normalized to Gaussia luciferase signals (mean ± SD, n = 5, Student's t-test, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "LacZ: 
HSF1: 3297
AMPKα1: 5562"
  },
  {
    "caption": "H, I Following treatment with 10 mM metformin overnight, endogenous AMPKα and HSF1 proteins were co-precipitated using anti-AMPKα agarose conjugates from lysates of immortalized Hsf1+/+MEFs (H).",
    "ncbi_link": "Hsf1: 15499"
  },
  {
    "caption": "HC: heavy chain. Endogenous HSF1-AMPKα interactions in immortalized Hsf1+/+ and Hsf1−/− MEFs were visualized in situ by PLA (I). Experimental details are described in Materials and Methods. Scale bars: 50 μm.",
    "ncbi_link": "Hsf1: 15499"
  },
  {
    "caption": "A In HEK293T cells that stably express an shRNA targeting the 3′ UTR of human HSF1, HSF1WT or HSF1S121A was expressed. Following treatment with 10 mM metformin overnight, the levels of HSF1 phosphorylation at Ser121 were detected by immunoblotting using a specific phospho-HSF1 Ser121 antibody (A8041, Assay Biotechnology).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "B Primary Ampkα1fl/fl; Ampkα2fl/fl MEFs were transduced with adenoviral GFP or Cre. Following treatment with 10 mM metformin overnight or treatment with 10 μM A-769662 for 3 h, HSF1 Ser121 phosphorylation was examined by immunoblotting.",
    "ncbi_link": "Cre: 
GFP: 
Ampkα1: 105787
Ampkα2: 108079"
  },
  {
    "caption": "C HSF1WT or HSF1S121A was co-expressed with either GFP or GST-AMPKαCA in HSF1-deficient HEK293T cells. HSF1 Ser121 phosphorylation was examined by immunoblotting.",
    "ncbi_link": "HSF1: 3297
AMPKα: 5562"
  },
  {
    "caption": "E, F HSF1 activities were measured by the dual reporter system in HSF1-deficient HEK293T cells. Either FLAG-HSF1WT or FLAG-HSF1S121A was co-expressed with LacZ orAMPKα1CA (E).",
    "ncbi_link": "LacZ: 
HSF1: 3297
AMPKα1: Q13131///5562"
  },
  {
    "caption": "E, F HSF1 activities were measured by the dual reporter system in HSF1-deficient HEK293T cells. Either FLAG-HSF1WT or FLAG-HSF1S121A was co-expressed with LacZ or AMPKα1CA (E). Following expression of HSF1WT or HSF1S121A, cells were treated with and without 10 mM metformin overnight (F) (mean ± SD, n = 5, one-way ANOVA, n.s., not significant, *P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "LacZ: 
HSF1: 3297
AMPKα1: 5562"
  },
  {
    "caption": "G, H FLAG-HSF1WT or FLAG-HSF1S121A plasmids were co-transfected with LacZ or AMPKα1CA plasmids into HSF1-deficient HEK293T cells for 3 days (G). Following transfection with FLAG-HSF1WT or FLAG-HSF1S121A plasmids for 3 days, HSF1-deficient HEK293T cells were treated with and without 10 mM metformin overnight (H). Nuclear proteins were extracted to measure HSF1-DNA binding by the ELISA-based DNA binding assay using anti-FLAG antibodies (mean ± SD, n = 3, one-way ANOVA, n.s., not significant, *P < 0.05, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "LacZ: 
HSF1: 3297
AMPKα1: 5562"
  },
  {
    "caption": "I, J HEK293T cells were sequentially transfected with control or AMPKα1/2-targeting siRNAs and dual HSF1 reporter plasmids. 24 h later, transfected cells were starved overnight before reporter activities were measured (mean ± SD, n = 6, Student's t-test, n.s., not significant, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "AMPKα1: 5562"
  },
  {
    "caption": "I, J HEK293T cells were sequentially transfected with control or AMPKα1/2-targeting siRNAs and dual HSF1 reporter plasmids. 24 h later, transfected cells were starved overnight before reporter activities were measured (mean ± SD, n = 6, Student's t-test, n.s., not significant, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "AMPKα1: 5562"
  },
  {
    "caption": "K, L FLAG-HSF1WT or FLAG-HSF1S121A plasmids were co-transfected with the dual HSF1 reporter plasmids into HSF1-deficient HEK293T cells for 2 days, followed by overnight starvation (mean ± SD, n = 5, Student's t-test, n.s., not significant, *P < 0.05, **P < 0.01).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "F-H HSF1WT or HSF1S121A plasmids were transfected into HSF1-deficient HEK293T cells. Transfected cells were heat-shocked at 43°C for 40 min. HSP mRNAs were quantitated by qRT-PCR following overnight recovery. HSF1-DNA binding was measured immediately after heat shock (mean ± SD, n = 3, Student's t-test, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "HSP: 
HSF1: 3297"
  },
  {
    "caption": "A, B Following treatment with 10 μM metformin for 3 days, the levels of HSF1 binding to endogenous HSP promoters were quantitated by chromatin IP (mean ± SD, n = 3, one-way ANOVA, **P < 0.01, ***P < 0.001). Normal rabbit IgG served as the negative control (A). Following the same treatment, HSP mRNA levels were quantitated by qRT-PCR (mean ± SD, n = 3, Student's t-test, ***P < 0.001) (B).",
    "ncbi_link": "HSP: "
  },
  {
    "caption": "C, D Following transfection with AMPKα1/2-targeting siRNAs for 2 days, WM115 cells were treated with 10 μM metformin for 3 days. HSP mRNA levels were quantitated by qRT-PCR (mean ± SD, n = 6, Student's t-test, n.s., not significant, *P < 0.05, **P < 0.01).",
    "ncbi_link": "HSP: 
AMPKα1: 5562"
  },
  {
    "caption": "C, D Following transfection with AMPKα1/2-targeting siRNAs for 2 days, WM115 cells were treated with 10 μM metformin for 3 days. HSP mRNA levels were quantitated by qRT-PCR (mean ± SD, n = 6, Student's t-test, n.s., not significant, *P < 0.05, **P < 0.01).",
    "ncbi_link": "HSP: 
AMPKα1: 5562"
  },
  {
    "caption": "I HEK293T cells stably expressing either scramble or HSF1-targeting shRNAs were treated with 10 μM metformin for 7 days. Individual proteins were detected by immunoblotting.",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "K, L Immortalized and RAS-transformed MEFs were treated with either 10 μM metformin (K) or different concentrations of glucose (L) for 7 days. Individual proteins were detected by immunoblotting.",
    "ncbi_link": "RAS: 15461"
  },
  {
    "caption": "M Following transfection with LacZ or polyQ79, HEK293T cells were grown under different concentrations of glucose for 5 days before measuring aggregate size.",
    "ncbi_link": "LacZ: "
  },
  {
    "caption": "A, B A2058 cells were transduced with lentiviral scramble or HSF1-targeting (hA6 and hA9) shRNAs. (A) Cell numbers were quantitated by Hoechst 33342 DNA staining (mean ± SD, n = 4, two-way ANOVA, ***P < 0.001). (B) Protein levels were measured by immunoblotting.",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "C A2058 cells stably expressing LacZ or HSF1 were grown in medium containing 4.5, 1.0, or 0.45 g/l glucose. Following treatment with 10 μM metformin, cell proliferation was measured by Hoechst 33342 DNA staining (mean ± SD, n = 5, two-way ANOVA, ***P < 0.001).",
    "ncbi_link": "LacZ: 
HSF1: 3297"
  },
  {
    "caption": "D, E 1 × 106 LacZ- or HSF1-expressing A2058 cells were transplanted into female NOD/SCID mice. One day after transplantation, metformin was administered via drinking water at 1 mg/ml. Tumor incidence (log-rank test; D) and volumes (E) were measured (mean ± SEM, two-way ANOVA n.s., not significant, *P < 0.05, **P < 0.01, ***P < 0.001). Tumor growth curves were fitted to exponential growth models to calculate tumor doubling time (DT).",
    "ncbi_link": "LacZ: 
HSF1: 3297"
  },
  {
    "caption": "H A2058 cells stably expressing FLAG-HSF1WT or FLAG-HSF1S121A were treated with 10 μM metformin for 7 days. Protein levels were measured by immunoblotting.",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "I A2058 cells stably expressing HSF1WT or HSF1S121A were grown in Corning®ultra-low attachment 96-well culture plates with 10 μM metformin and different concentrations of glucose for 7 days, 10,000 cells per well. Viable cells were counted by Guava flow cytometer using ViaCount® reagent (mean ± SEM, n = 8, Student's t-test, n.s., not significant, **P < 0.01, ***P < 0.001).",
    "ncbi_link": "HSF1: 3297"
  },
  {
    "caption": "J Tukey box plots showing the inverse correlation between AMPKα Thr172 phosphorylation and HSP mRNA expression in ccRCC. Patients were stratified on the median value of AMPKα Thr172 phosphorylation reverse-phase protein array (RPPA) scores (Student's t-test).",
    "ncbi_link": "HSP: "
  },
  {
    "caption": "A Co-immunoprecipitation of endogenous STING with WIPI1/2-Myc in MEFs transfected with Myc-tagged WIPI1 or WIPI2. The cells were treated with or without cGAMP for 2 h and the WIPI1/2-Myc precipitates were analyzed by western blot using anti-STING. B Co-immunoprecipitation of endogenous WIPI2 with HA-tagged STING, STING-R238A or STING-S366A from HEK293T cells stably expressing STING-HA STING-R238A-HA or STING-S366A-HA. The cells were treated with or without cGAMP for 2 h.",
    "ncbi_link": "HA: 
Myc: 
STING: 340061
WIPI1: 55062
WIPI2: 74781"
  },
  {
    "caption": "Co-immunoprecipitation of endogenous STING with Myc- WIPI2 or the indicated WIPI2 mutants from MEFs transfected with the indicated plasmids.",
    "ncbi_link": "Myc: 
WIPI2: 74781"
  },
  {
    "caption": "A WIPI2-GFP puncta in MEFs stably expressing GFP-tagged WT or mutant WIPI2. The cells were treated with cGAMP for 2 h or Torin1 for 1 h. B Statistical analysis of the number of WIPI2-GFP puncta in cells treated as in (A).",
    "ncbi_link": "GFP: 
WIPI2: 74781"
  },
  {
    "caption": "F LC3 and p62 level in HEK293T cells stably expressing HA-tagged WT or mutant STING. The cells were treated with or without cGAMP for 4 h.",
    "ncbi_link": "HA: 
STING: 340061"
  },
  {
    "caption": "C Co-immunoprecipitation of endogenous WIPI2 with STING-HA from HEK293 cells stably expressing STING-HA with or without BECN1 deletion. The cells were treated with or without Torin1 for 3 h.",
    "ncbi_link": "HA: 
BECN1: 8678
STING: 340061"
  },
  {
    "caption": "E Co-immunoprecipitation of endogenous STING with Myc-tagged WT or mutant WIPI2 from MEFs treated with or without VPS34-IN1 for 2 h.",
    "ncbi_link": "Myc: 
WIPI2: 74781"
  },
  {
    "caption": "A, B Localization of endogenous WIPI2, WIPI1, ATG16L1 (A) or Myc-tagged WT WIPI2 or WIPI2 mutants (B) in MEFs transfected with Cy3 labeled-ISD (1 μg/ml). ISD, interferon stimulatory DNA.",
    "ncbi_link": "Myc: 
WIPI2: 74781"
  },
  {
    "caption": "A Wipi2- or Sting-deleted MEFs were treated with Ara-C for 12 h, and then cultured in Ara-C-free medium. After 24 h, the cells were lysed and analyzed by western blot using the indicated antibodies. B Statistical analysis of the protein level of phospho-TBK1 (Ser172) and STING in cells treated as in (A). The relative phospho-TBK1 level was normalized to TBK1, the relative STING level was normalized to Actin.",
    "ncbi_link": "Sting: 72512
Wipi2: 74781"
  },
  {
    "caption": "C-E MEFs with Wipi2 or Sting deletion (C), Wipi2-KO MEFs with transfection of Myc-tagged WT or mutant WIPI2 (D), or Sting-KO MEFs with transfection of HA-tagged WT or mutant STING (E), were treated with Ara-C for 12 h and then cultured in Ara-C-free medium for another 24 h. Total mRNA was extracted and the Ifnb1 mRNA level was measured by real-time PCR and normalized to Actb mRNA. 2RE, WIPI2-R108E/R125E.",
    "ncbi_link": "HA: 
Myc: 
Actb: 11461
Ifnb1: 15977
Sting: 72512
STING: 340061
Wipi2: 74781
WIPI2: 74781"
  },
  {
    "caption": "F Sting-KO MEFs with transfection of HA-tagged WT or mutant STING were treated with cGAMP for the indicated time. The cells were lysed and analyzed by western blot using the indicated antibodies.",
    "ncbi_link": "HA: 
Sting: 72512
STING: 340061"
  },
  {
    "caption": "Western blots showing co-immunoprecipitation of GAPDH from the total lysate (left) and isolated mitochondria (right) of brain tissues of wild-type (WT) and transgenic R6/2 (HD) mice with anti-GAPDH antibody. The presence of huntingtin was examined with anti-huntingtin antibody and anti-polyglutamine antibody, respectively. Co-immunoprecipitated huntingtin or polyglutamine (polyQ) was normalized to GAPDH. Left: n = 2. *P = 0.03; **P = 0.02. Right: One representative experiment from two repeats.",
    "ncbi_link": "huntingtin: 3064"
  },
  {
    "caption": "Representative Western blot showing levels of mitochondrial proteins, as indicated by the presence of aconitase, VDAC, and Tom20, in the total lysates of PC12 cells with Q23 or Q74 before (represented as NT: no treatment) and after overexpression of inactive GAPDH (represented as G). n = 3. *P < 0.035; **P = 0.001; #P = 0.001.",
    "ncbi_link": "GAPDH: 24383"
  },
  {
    "caption": "Representative Western blot showing levels of mitochondrial proteins in the total lysates of mice striatal cells with Q7 or Q111 before (NT) and after overexpression of inactive GAPDH (G). n = 2. *P = 0.006; **P = 0.007; #P = 0.001.",
    "ncbi_link": "GAPDH: 14433"
  },
  {
    "caption": "Determination of mitochondrial membrane potential using JC-1 in different HD models and control cells (MMP, ΔΨm). The difference in membrane potential between NT (no inactive GAPDH overexpression) and G (inactive GAPDH overexpression) in cells with expanded polyglutamine repeats (PC12 cells with Q74 and HD patient-derived fibroblasts) was not statistically significant. n = 3.",
    "ncbi_link": "GAPDH: 24383
GAPDH: 2597"
  },
  {
    "caption": "ATP levels in normal and HD patient-derived fibroblasts. The difference in ATP levels between NT (no inactive GAPDH overexpression) and G (inactive GAPDH overexpression) in HD patient-derived fibroblasts was not statistically significant. n = 2.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Immunofluorescence of normal and HD patient-derived fibroblasts, with and without overexpression of inactive GAPDH, stained for late endosome with anti-Rab7 antibody and mitochondria with anti-Tom20 antibody. Images were acquired at 63× magnification, and brightness and contrast of all images were adjusted by 30%. Correlation coefficient (juvenile): **P = 0.007; *#P = 0.005. Mitochondrial interconnectivity (juvenile): ##P = 0.001; ##*P = 0.02. Correlation coefficient (adult): §§P = 0.001; *§P = 0.005. Mitochondrial interconnectivity (adult): ≠≠P = 0.043; ≠≠*P = 0.015.",
    "ncbi_link": "GAPDH: 2597"
  },
  {
    "caption": "Representative Western blot showing levels of mitochondrial proteins, as indicated by the presence of aconitase, VDAC, and Tom20, in the total lysates of PC12 cells with Q23 or Q74 in an in vitro reconstituted micro-mitophagic system. NT: no inactive GAPDH treatment; G: inactive GAPDH treatment. n = 3. *P = 0.0007; **P = 0.001; #P = 0.008.",
    "ncbi_link": "GAPDH: 24383"
  },
  {
    "caption": "Western blot showing the level of Atg5 expression in the Atg5+/+ (WT) and Atg5−/− (KO) MEF cells.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "Western blot showing levels of GAPDH association with mitochondria in Atg5 KO MEF cells. n = 2. *P = 0.04.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "Western blot showing relative mitochondrial mass in the total lysates of Atg5 KO MEF cells. n = 2. **P = 0.03; ***P = 0.02. Expression levels of Q23 or Q73 were detected with anti-His antibody.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "Western blot showing relative mitochondrial mass in the total lysates of Atg5 KO MEF cells without and with recombinant inactive GAPDH treatment (represented as NT and G, respectively). n = 2. *P = 0.02; **P = 0.03; *#P = 0.03; #P = 0.005.",
    "ncbi_link": "Atg5: 11793
GAPDH: 14433"
  },
  {
    "caption": "(C) ChIP-qPCRs at ARAP1, RFX5-GBAT2, WDR74 and HAUS5 promoters for IgG and DVL3 in MDA-MB-468 (NTC, shA DVL3, and shB DVL3).",
    "ncbi_link": "ARAP1: 116985
DVL3: 1857
HAUS5: 23354
RFX5: 5993
GBAT2: 101927886
WDR74: 54663"
  },
  {
    "caption": "(D) ChIP-qPCRs at RFX5-GBAT2, COX14, HLA-E and PSMB8 promoters for IgG and DVL3 in MCF7 (NTC, shA DVL3, and shB DVL3).",
    "ncbi_link": "COX14: 84987
DVL3: 1857
HLA-E: 3133
PSMB8: 5696
RFX5: 5993
GBAT2: 101927886"
  },
  {
    "caption": "(E) RT-qPCR-based analysis of expression changes of RFX5, GBAT2, WDR74, HCG15, POU2F3, SNORD3B, APOC1P1, HLA-A, TAP1, PSMD8, PDG1 and JUNB genes in MDA-MB-468 (NTC, shA DVL3, and shB DVL3) cells. (F) RT-qPCR-based analysis of expression changes of RFX5, GBAT2, PCAT6, ZNF672, SSC5D, APOC1P1, HLA-A, HLA-F and TAP1 genes in MCF7 (NTC, shA DVL3, and shB DVL3) cells. D ",
    "ncbi_link": "APOC1P1: 342
DVL3: 1857
PDG1: 2819
HCG15: 414761
HLA-A: 3105
HLA-F: 3134
JUNB: 3726
PCAT6: 100506696
POU2F3: 25833
PSMD8: 5714
RFX5: 5993
GBAT2: 101927886
SNORD3B: 26851
SSC5D: 284297
TAP1: 6890
WDR74: 54663
ZNF672: 79894"
  },
  {
    "caption": "(C) ChIP-qPCRs at ARAP1, RFX5-GBAT2, KDM5B, APOC1P1, and PSMB8 promoters for IgG and H3K4me3 in MDA-MB-468 (NTC, shA DVL3, and shB DVL3).",
    "ncbi_link": "APOC1P1: 342
ARAP1: 116985
DVL3: 1857
KDM5B: 10765
PSMB8: 5696
RFX5: 5993
GBAT2: 101927886"
  },
  {
    "caption": "(D) ChIP-qPCRs at RFX5-GBAT2, PCAT6, APOC1P1 and HAUS5 promoters for IgG and H3K4me3 in MCF7 (NTC, shA DVL3, and shB DVL3).",
    "ncbi_link": "APOC1P1: 342
DVL3: 1857
HAUS5: 23354
PCAT6: 100506696
RFX5: 5993
GBAT2: 101927886"
  },
  {
    "caption": "(C) ChIP-qPCRs at ARAP1, RFX5-GBAT2, and PSMB8 promoters for IgG and KMT2D in MDA-MB-468 (NTC, shA DVL3, and shB DVL3).",
    "ncbi_link": "ARAP1: 116985
DVL3: 1857
PSMB8: 5696
RFX5: 5993
GBAT2: 101927886"
  },
  {
    "caption": "(D) An assembly of IgG (first row), DVL3 (second row), H3K27ac (third row), and H4K8ac peak (fourth row) ChIP-Seq data in MDA-MB-468 for the PRDM10, TRIM26, BTN2A1, PNRC2, and MR1 genes, visualized by IGV. The green rectangular bars are the locations of the statistically-qualified peak of H3K27ac or H4K8ac in MDA-MB-468.",
    "ncbi_link": "BTN2A1: 11120
MR1: 3140
PNRC2: 55629
PRDM10: 56980
TRIM26: 7726"
  },
  {
    "caption": "(E) An assembly of IgG (first row), DVL3 (second row), H3K27ac (third row), and H4K8ac peak (fourth row) ChIP-Seq data in MCF7 for the WDR74, YWHAQ, CDNF/HSPA14, BTN2A1, and MR1 genes, visualized by IGV. The turquoise and purple rectangular bars are the locations of the statistically-qualified peak of H3K27ac or H4K8ac in MCF7, respectively.",
    "ncbi_link": "BTN2A1: 11120
CDNF: 441549
HSPA14: 51182
MR1: 3140
WDR74: 54663
YWHAQ: 10971"
  },
  {
    "caption": "(D) RT-qPCR-based analysis of expression changes of DVL3 in MDA-MB-468 (NTC, shA DVL3, and shB DVL3) cells. (E) RT-qPCR-based analysis of expression changes of KMT2D in MDA-MB-468 (NTC, shA DVL3, and shB DVL3) cells. (F) RT-qPCR-based analysis of expression changes of DVL3 in MCF7 (NTC, shA DVL3, and shB DVL3) cells. (G) RT-qPCR-based analysis of expression changes of KMT2D in MCF7 (NTC, shA DVL3, and shB DVL3) cells. (H ",
    "ncbi_link": "DVL3: 1857
KMT2D: 8085"
  },
  {
    "caption": "(H) Immunofluorescence of KMT2D localization in MDA-MB-468 cells. The cells were probed with KMT2D antibody (red). The nucleus was stained with DAPI (blue) and the actin filaments (green) were stained with Phalloidin. Merge of KMT2D (red) and nuclear staining (blue) is shown as KMT2D/DAPI, merge of KMT2D (red) and actin (green) is shown as KMT2D/ACTIN, and, merge of KMT2D (red), nuclear staining (blue) and actin (green) is shown as MERGE for NTC, shA DVL3 and shB DVL3 cells. Scale bar: 10µm",
    "ncbi_link": "DVL3: 1857"
  },
  {
    "caption": "(C) IVIS images showing representative tumors generated by injecting luciferase-expressing MDA-MB-468 cells (NTC, shA DVL3 or shB DVL3) in the mammary fat pad of SCID mice. Color scale (luminescent signal intensity): blue, least intense signal; red, most intense signal. (D) Quantification of luminescence changes in tumors generated by injecting luciferase-expressing MDA-MB-468 cells (NTC, shA DVL3 or shB DVL3) in the mammary fat pad of SCID mice, Average luminescence was used to measure volume of tumor; n ≥ 9. ( ",
    "ncbi_link": "luciferase: 
DVL3: 1857"
  },
  {
    "caption": "(G) IVIS images showing representative tumors generated by injecting luciferase-expressing MCF7 cells (NTC, shA DVL3) in the mammary fat pad of SCID mice. Color scale (luminescent signal intensity): blue, least intense signal; red, most intense signal. (H) Quantification of luminescence changes in tumors generated by injecting luciferase-expressing MCF7 cells (NTC, shA DVL3) in the mammary fat pad of SCID mice. Average luminescence was used to measure volume of tumor. n=7.",
    "ncbi_link": "DVL3: 1857"
  },
  {
    "caption": "(A) Immunofluorescence of HA-tagged DVL3 localization in MDA-MB-468 cells. The cells were probed with an HA antibody (red). The nucleus was stained with DAPI (blue) and the actin filaments (green) were stained with Phalloidin. Merge of actin (green) and nuclear staining (blue) is shown as ACTIN/DAPI, merge of DVL3 (red) and nuclear staining (blue) is shown as HA/DAPI, merge of DVL3 (red) and actin (green) is shown as HA/ACTIN, and, merge of DVL3 (red), nuclear staining (blue) and actin (green) is shown as MERGE for empty vector (EV), HA-DVL3-WT and HA-DVL3-NESm transient transfected cells. Scale bar: 10µm.",
    "ncbi_link": "HA: 
DVL3: 1857"
  },
  {
    "caption": "(B) RT-qPCR-based analysis of expression changes of DVL3 in stable MDA-MB-468 (EV, HA-DVL3-NESm) cells. (C) RT-qPCR-based analysis of expression changes of KMT2D in stable MDA-MB-468 (EV, HA-DVL3-NESm) cells. (D) RT-qPCR-based analysis of expression changes of ARAP1 , RFX5, GBAT2, WDR74, SNORD3D, HAUS5, TAP1, HLA-A, PDG1, and, MR1 in stable MDA-MB-468 (EV, HA-DVL3-NESm) cells. (E ",
    "ncbi_link": "HA: 
ARAP1: 116985
DVL3: 1857
PDG1: 2819
HAUS5: 23354
HLA-A: 3105
KMT2D: 8085
MR1: 3140
RFX5: 5993
GBAT2: 101927886
SNORD3D: 780854
TAP1: 6890
WDR74: 54663"
  },
  {
    "caption": "All analyses were performed using AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.A) Immunohistochemistry analysis of small intestinal sections, using the indicated antibodies.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "All analyses were performed using AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.B) Western blot analysis with protein extracts obtained from ex vivo-purified intestinal crypts and probed with the indicated antibodies.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "All analyses were performed using AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.C) Haematoxylin and eosin staining of sections prepared from different intestinal tracts.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "All analyses were performed using AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.D) Immunohistochemistry analysis of small intestinal sections, using specific antibodies for the proliferation marker KI67.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "All analyses were performed using AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.E) Expression analysis by qRT-PCR of the proliferation related markers indicated in the figure using RNA extracted from intestinal crypts. Graphs show mean ± SD for three replicates.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "A) PAS and (B) Alcian blue staining of sections prepared from the different intestinal tracts isolated from AhCre Eed+/+ and AhCre Eedfl/fl mice (n=5) injected with β-naphthoflavone and sacrificed after 15 days.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "D) Immunohistochemistry analyses in AhCre Eed+/+ and AhCre Eedfl/fl mice injected with β-naphthoflavone and sacrificed after 15 days using a lysozyme-specific antibody (upper panels: LYZ, a Paneth cell-specific marker). Histochemical assay probing for alkaline phosphatase activity is presented in the middle panels (ALPI, an enterocyte-specific marker). Combined Ki67 immunohistochemistry and histochemical Alcian blue staining is presented in the lower panels (Alcian/KI67).",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "E) GFP expression from an Lgr5-eGFPtransgene identifying LGR5+ ISCs in near-native agarose-embedded sections from Eed+/+ and Eed-/- mice at 30 days from the first β-naphthoflavone administration. Cell nuclei were counterstained with DAPI.",
    "ncbi_link": "Eed: 13626"
  },
  {
    "caption": "A) Radiation-induced intestinal regeneration: AhCre Eed+/+ and AhCre Eedfl/fl mice were injected with β-naphthoflavone, irradiated with 10 Gy 15 days later, and sacrificed 4 and 8 days after irradiation. Sections prepared from the different intestinal tracts were stained with haematoxylin and eosin (n=6).",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "B) Immunohistochemistry analyses in AhCre Eed+/+ and AhCre Eedfl/fl mice treated as in A using H3K27me3 and KI67 specific antibodies at 8 days post-irradiation.C) Quantification (mean ± SD) of KI67 positive cells per crypt (B). More than 100 crypts were scored for each condition.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "D) In vitro organoids formation using crypts isolated from AhCre Eed+/+ and AhCre Eed-/- mice 15 days after the first β-naphthoflavone injection. Organoids pictures were taken 5 days later at low and higher magnification (insets).",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "A) Volcano plot showing the expression changes with a minimal fold change of 3 (FC=3) at genome-wide levels in AhCre Eed-/- crypts relative to AhCre Eed+/+ crypts 15 days after β-naphthoflavone administration.",
    "ncbi_link": "Cre: 
Ah: 11622
Eed: 13626"
  },
  {
    "caption": "B) Bar plot showing the percentage of H3K27me3-positive promoters among the differentially regulated genes in Eed-/- crypts. All gene promoters and 5 independent random sampling of 167 gene promoters extracted the mouse genome are presented as specificity controls.",
    "ncbi_link": "Eed: 13626"
  },
  {
    "caption": "C) Intensity profiles for H3K27me3 and SUZ12 occupancy at the promoters of up-regulated genes with respect to down-regulated genes in Eed-/- crypts.",
    "ncbi_link": "Eed: 13626"
  },
  {
    "caption": "D) Genomic snapshots of the Cdkn2a locus showing SUZ12 occupancy and H3K27me3 deposition at the promoter regions of both the p16 and the ARF isoforms.",
    "ncbi_link": "ARF: 12578
Cdkn2a: 12578
p16: 12578"
  },
  {
    "caption": "E) Genomic snapshots of the RNAseq profile of the Cdkn2a locus in AhCre Eed+/+ and AhCre Eed-/- crypts 15 days after β-naphthoflavone administration.",
    "ncbi_link": "Cre: 
Ah: 11622
Cdkn2a: 12578
Eed: 13626"
  },
  {
    "caption": "F) Expression analysis by qRT-PCR (mean ± SD) of both Cdkn2a isoforms (p16Ink4A and p19Arf) in AhCre Eed+/+ and AhCre Eed-/- crypts 15 days after β-naphthoflavone administration.",
    "ncbi_link": "Cre: 
Ah: 11622
Cdkn2a: 12578
p16Ink4A: 12578
p19Arf: 12578
Eed: 13626"
  },
  {
    "caption": "G) Gene set enrichment analysis (GSEA) using specific secretory and enterocytic transcriptional signatures with respect to the list of up-regulated genes in Eed-/- crypts.",
    "ncbi_link": "Eed: 13626"
  },
  {
    "caption": "A) Haematoxylin and eosin (top panels) and PAS staining (bottom panels) of sections prepared from different intestinal tracts in AhCre Cdkn2a-/- Eed+/+ and AhCre Cdkn2a-/- Eedfl/fl mice 15 days after the first β-naphthoflavone administration (n=5).",
    "ncbi_link": "Cre: 
Ah: 11622
Cdkn2a: 12578
Eed: 13626"
  },
  {
    "caption": "C) Immunhistochemistry analysis using anti-KI67 antibody of intestinal sections prepared from AhCre Cdkn2a-/- Eed+/+ and AhCre Cdkn2a-/- Eedfl/fl mice 15 days after the first β-naphthoflavone administration.",
    "ncbi_link": "Cre: 
Ah: 11622
Cdkn2a: 12578
Eed: 13626"
  },
  {
    "caption": "D) Radiation-induced intestinal regeneration: AhCre Cdkn2a-/- Eed+/+ and AhCre Cdkn2a-/- Eedfl/fl mice (n=6) were injected with β-naphthoflavone, irradiated with 10 Gy 15 days later, and sacrificed 8 days after irradiation. Sections prepared from the different intestinal tracts were stained with haematoxylin and eosin (first panels) and Alcian Blue (last panels). Sections were also stained for immunohistochemistry analysis (second and third panels) using H3K27me3 and Ki67-specific antibodies.",
    "ncbi_link": "Cre: 
Ah: 11622
Cdkn2a: 12578
Eed: 13626"
  },
  {
    "caption": "C) Expression analysis by qRT-PCR (mean ± SD) of the Goblet cell markers (Atoh1, Gfi1, Spdef), early secretory precursor cells (Dll1), NOTCH targets (Hes1, Olfm4) and intestinal stem cells (Lgr5, Rnf43) in wild type intestinal crypts purified 38hrs after treatment with the NOTCH inhibitor DBZ. DMSO served as vehicle negative control (n=4).",
    "ncbi_link": "Atoh1: 11921
Dll1: 13388
Gfi1: 14581
Hes1: 15205
Lgr5: 14160
Olfm4: 380924
Rnf43: 207742
Spdef: 30051"
  },
  {
    "caption": "D) ChIP analysis of Atoh1 and Gfi1 loci using H3K27me3 specific antibody. The same crypts described in C were used. H3K27me3 levels were normalized on Histone H3 density (percentage of H3 signal). Graphs show mean ± SD.",
    "ncbi_link": "Atoh1: 11921
Gfi1: 14581"
  },
  {
    "caption": "a, Thymi from wild-type (WT) or Atg5-/- embryos were transplanted under the kidney capsule of wild-type recipients and analysed 6 weeks later. The average cellularities ± s.d. are shown; n = 5.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, Normal compartmentalization of Atg5-/- grafts in cytokeratin-8-positive (red; K8) cortical and cytokeratin-5-positive (green; K5) medullary regions; n = 8.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, Expression of MHC class I and II on cTECs or mTECs from Atg5-/- to wild-type (WT) grafts (red), or wild-type to wild-type grafts (blue). Staining controls are depicted in grey; data are representative of three experiments. d",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, RT-PCR analysis of autoimmune regulator (Aire) and TRA expression in mTECs isolated from Atg5-/- to wild-type, or wild-type to wild-type grafts. Expression of β-actin (Actb), intestinal trefoil factor (Tff3), casein 2 (Csn2) and salivary protein 1 (Spt1) are also shown (5-fold serial dilutions). Data are representative of two experiments.",
    "ncbi_link": "Actb: 11461
Aire: 11634
Atg5: 11793
Csn2: 12991
Spt1: 20770
Tff3: 21786"
  },
  {
    "caption": "a, Polyclonal T-cell development in Atg5-/- to wild-type (WT), or wild-type to wild-type grafts. The top dot plots show CD4 and CD8 staining; the bottom dot plots show expression of CD25 and Foxp3 by CD4 SP thymocytes; n ≥ 5.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "b, Atg5-/- or wild-type lobes were grafted into TCR-HA transgenic recipients. Graft cellularity ± s.d. and the expression of the transgenic TCR on CD4 SP cells were analysed after 6 weeks. The frequency ± s.d. of TCR-HA+ cells among CD4 SP cells was 32.1% ± 3.2% in wild-type to TCR-HA, and 19.6% ± 4.3% in Atg5-/- to TCR-HAlobes; P = 1.8 × 10-8 (n ≥ 14).",
    "ncbi_link": "TCR: 110066///21577///21473///110067
TCR: 21577///21473///110067///110066
Atg5: 11793
TCR: 110067///110066///21577///21473"
  },
  {
    "caption": "c, Atg5-/- or wild-type lobes were grafted into AND transgenic mice. Graft cellularity ± s.d. and the expression of the transgenic TCR (Vb3-Va11) on CD4 SP cells were analysed after 6 weeks. The frequency ± s.d. of Vb3-Va11+ CD4 SP cells was 93.5% ± 0.2% in wild-type to ANDlobes (n = 3) and 97.9% ± 1.1% (n = 6) in Atg5-/- to ANDlobes (P = 9 × 10-4).",
    "ncbi_link": "TCR: 21577///21473///110067///110066
Atg5: 11793
AND: 21595///111620"
  },
  {
    "caption": "d, Thymi from wild-type or Atg5-/- embryos were grafted into P14, OT-I or HY TCR-transgenic recipients. The dot plots show the expression of the transgenic TCR V-segments on CD8 SP cells. Thymus cellularities ± s.d. are shown in the respective bar diagrams. Data are representative of n = 4 (P14), n ≥ 4 (OT-I) and n ≥ 2 (HY).",
    "ncbi_link": "TCR: 21473///21577///110067///110066
Atg5: 11793"
  },
  {
    "caption": "e, Thymi from wild-type or (BALB/c3C57BL/6)F1 Atg5-/- embryos were transplanted into (BALB/c3C57BL/6)F1 recipients. Six weeks after grafting, expression of the I-Ea52-68-I-Ab complex on cTECs was analysed using the monoclonal antibody Y-Ae. Atg5-/- cTECs are shown in red; wild-type cTECs are shown in blue. Control stainings are shown in orange (Atg5-/-) and green (wild type). Data are representative of two independent experiments.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "Atg5-/- or wild-type (WT) lobes were grafted into athymic (nu/nu) mice (nu/nuAtg5-/- or nu/nuWT, respectively). Data are representative of three experiments with n ≥ 4. a, Expression of activation markers on lymph node CD4 T cells in nu/nuAtg5-/- or nu/nuWT chimaeras.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "c, The appearance of nu/nuAtg5-/- or nu/nuWT chimaeras. The colon (arrow) and uterus (arrowhead) are highlighted; note the absence of fat pads (asterisk) in nu/nuAtg5-/- chimaeras.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "d, Haematoxylin and eosin staining of organs from nu/nuAtg5-/- or nu/nuWT chimaeras. Arrows indicate infiltrates.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(G and H) Calhm6 mRNA expression measured by qPCR in naïve or IFN-γ (10 ng/ml) primed (6 h) BMDM stimulated with (G) Poly(I:C) (50 μg/ml) (one representative experiment of two is shown, n = 2 mice, biological replicates), or (H) Zymosan (100 μg/ml) for 2 to 24h (one representative experiment is shown, n = 3 mice, biological replicates).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "CFU/g of spleen are shown (B) after 24 h (pooled results from two independent experiments, WT mice = 9, Calhm6-/- mice = 12, Man Whitney test), (C) 72 h (pooled results from two independent experiments, WT mice = 16, Calhm6-/- mice = 17, Man Whitney test)",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "Serum collected from infected mice at peak infection (day 3) and serum cytokines quantified using LEGENDplex Mouse Inflammation Panel assay to determine IFN-γ (F), IL-6 (G) and IL-10 (H) concentration (pooled results from two independent experiments, WT mice = 16, Calhm6-/- mice = 17, Mann Whitney test).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(F-J) WT and Calhm6-/- mice were injected i.p. with Poly(I:C) (200 μg/mouse) or PBS for 3 h (F-H) or 12 h (I-J), spleens were collected and processed as in (A-E). Representative contour plots (F, I), pooled frequency of IFN-γ+ in CD3-NK1.1+ cells of WT vs Calhm6-/- mice (G,J) and ratio of IFN-γ+ cells that are NK1.1+ or CD3+ normalised as in C (H) (For Poly(I:C) 3 h: pooled results from two independent experiments, Poly(I:C) WT mice = 10, Calhm6-/- mice = 10, control WT mice = 2, Calhm6-/- mice = 2, One way ANOVA with multiple comparisons. For Poly(I:C) 12 h: results from one experiment, Poly(I:C) WT mice = 6, Calhm6-/- mice = 5, control WT mice = 1, Calhm6-/- mice = 1 mice, One-way ANOVA with multiple comparisons).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(A-B) WT and Calhm6-/- mice were injected i.p. with Poly(I:C) (200 μg/mouse) or PBS. On day 3 spleens were collected, stained with antibodies against NK cell-maturation markers and analysed by flow cytometry. Representative contour plots (A) and pooled flow cytometry results (B) are shown (results from one experiment, Poly(I:C) WT mice = 5, Calhm6-/- mice = 5, control WT mice = 2, Calhm6-/- mice = 2 mice, One-way ANOVA with multiple comparisons).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(F) NO production in WT and Calhm6-/- BMDM treated overnight with LPS or Poly(I:C) quantified with a Griess test on cell supernatant (results from one experiment, WT mice = 3, Calhm6-/- mice = 3, Kruskal Wallis test with multiple comparisons).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(G) BMDM with or without IFN−γ priming were grown overnight in antibiotic free medium. Cells were infected with L. monocytogenes (MOI 1) for 30 min. Gentamicin (5 ng/ml) was then added to the medium to kill extracellular bacteria. At 0, 4 and 8 h cells were harvested, lysed with 0.1% Triton X-100 and the lysate was plated on antibiotic free BHI plates for 24 h, and CFU were quantified (pooled results from three independent experiments, WT mice = 3, Calhm6-/- mice = 3, Two-way ANOVA test).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(D-G) BMDM were transduced with a retroviral vector expressing CALHM6-eGFP. BMDM (3x105) were plated on coverslips and pre-treated with IFN-γ and LPS for 6 h. (D) Freshly isolated primary CD3-NK1.1+ cells isolated from mouse spleens were added for 0, 10, 20, or 40 min on top of plated BMDMs that were generated from bone marrow cells transduced with a retroviral vector expressing CALHM6-eGFP. The interacting cells were then fixed and stained with phalloidin to identify actin and DAPI to identify nucleus. Synaptic interaction between BMDM and NK cell is indicated by white arrowheads; entire collapsed imaging Z-stack is shown. (E) Images were blinded and CALHM6-eGFP polarisation towards CD3-NK1.1+ cells manually scored only in Z-slices where BMDM-NK interaction was identified (p-value calculated by two-way ANOVA of polarisation and time points). Numbers on top of each bar indicate number of synapses scored for that time point. (F) IgG2a-opsonised sRBC labelled with PHK26 were added on top of plated CALHM-eGFP-expressing BMDM. One single Z-slice containing BMDM-sRBC interaction plane is shown. Synaptic interaction between BMDM and sRBC cell is indicated by white arrowheads (G) Quantified results of experiment in F. Numbers on top of each bar indicate number of synapses scored for that time point. Longer time points were not possible to score for opsonised sRBC because of the speed of the phagocytosis as sRBC were quickly internalised. Images taken with 60x objective (p-value calculated by two-way ANOVA of polarisation and time points).",
    "ncbi_link": "eGFP: 
CALHM6: 215900"
  },
  {
    "caption": "(B) WT or Calhm6-/- BMDM stimulated with IFN-γ (10 ng/ml) for 24 h were lysed with 1% Triton X100-containing buffer with cOmplete protease inhibitor cocktail and treated with increasing concentrations of DTT. The samples, without boiling, were resolved by SDS-PAGE gel (one representative experiment of two is shown, n = 4 mice). Lack of DTT influences solubilisation of GADPH monomer, and its detection for immunoblotting.",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(G) Current-voltage (I-V) relations for WT-mCALHM6, E119R-mCALHM6 and control (ASO) in 2-mM Ba2+ bath solution (pooled individual whole-cell patches, WT-mCALHM6 n = 13, E119R-mCALHM6 n = 4, control = 4, SEM error bars).",
    "ncbi_link": "CALHM6: 215900"
  },
  {
    "caption": "(A) Fura-2 fluorescence ratio (F340/380) recorded in N2a cells expressing human CALHM1 (hCALHM1), mouse CALHM6 (mCALHM6) or control (vector) in response to removal and subsequent add-back of extracellular Ca2+. Traces representative of four independent experiments for each, normalized to baseline ratio. Right: Resting F340/380 ratio in N2a cells expressing hCALHM1, mCALHM6 or vector in 2 mM Ca2+ (the error bars represent SEM).",
    "ncbi_link": "CALHM1: 255022
CALHM6: 215900"
  },
  {
    "caption": "(E) Steady-state ATP release from activated macrophages: BMDMs were plated at 150,000 cells/well in a 48-well plate, and incubated for 3 h with Poly(I:C) (50 μg/ml), LPS (100 ng/ml) and ATPase inhibitor ARL67156 (1 mM) in culture medium. Control cells were incubated with 1 mM ARL67156 only. ATP release (nM) measured using Sigma ATP Bioluminescent Assay: WT without stimulation: 9.12 ± 0.76; WT with stimulation: 22.16 ± 1.83; Calhm6-/- cells without stimulation: 8.76 ± 0.55; KO cells with stimulation: 12.19 ± .75. (pooled results from three independent experiments, WT mice = 3, Calhm6-/- mice = 3, Two-tailed unpaired Student's T test, error bars represent SEM).",
    "ncbi_link": "Calhm6: 215900"
  },
  {
    "caption": "(H) The expression  level of AURKB  in PANC-1  cells transfected with control or ROR1   siRNA and in ROR1high or ROR1low cells from  S2-VP10 and PDO#1 xenografts  (n = 3). Data information: Data are presented as mean ± s.e.m., two-sided t-test. *, p < 0.05; n.s., not significant.",
    "ncbi_link": "AURKB: 9212
ROR1: 4919"
  },
  {
    "caption": "(I) Western blot  analysis of ROR1, AURKB, and β-actin in  S2-VP10 and S2-013  cells transfected with control or ROR1   siRNA.",
    "ncbi_link": "ROR1: 4919"
  },
  {
    "caption": "(K)  Organoid  formation assay  of ROR1high or ROR1low cells derived from S2-VP10 EGFP  (control) or S2-VP10 AURKB-EGFP xenografts  (n = 3, biological replicates). Representative images and the number of organoids   are shown. Data information: Scale bars, 1 mm (K). Data are presented as mean ± s.e.m., two-sided t-test. *, p < 0.05; n.s., not significant.",
    "ncbi_link": "EGFP: 
AURKB: 9212"
  },
  {
    "caption": "(L) Western blot  analysis of ROR1, AKT, phospho-AKT  (Ser473), and β-actin in S2-VP10  and S2-013 cells transfected with control or ROR1   siRNA.",
    "ncbi_link": "ROR1: 4919"
  },
  {
    "caption": "(N) Western blot  analysis of ROR1, c-Myc, phospho-RB  (Ser780), E2F1, and  β-actin in  S2-VP10 and S2-013  cells transfected with control or ROR1  siRNA.",
    "ncbi_link": "ROR1: 4919"
  },
  {
    "caption": "(A)-(C) Representative images of ROR1, mCherry, and aSMA staining  in the  primary tumor  (pancreas) (A) and metastatic lesions  in the lung  (B) and mesenteric lymph node (C) after orthotopic transplantation of S2-VP10-mCherry  cells into the pancreas  of BRJ mice. Data information: Scale bars, 100 µm",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "(A), H3K4me1,  K3K4me3, H3K27ac, and open chromatin  profiles  around the ROR1  gene by  CUT&RUN and ATAC-sequencing in cultured S2-VP10 cells (A) The ROR1  promoter (blue-shaded boxes) and enhancer elements (green-shaded box) of ROR1  are indicated.",
    "ncbi_link": "ROR1: 4919"
  },
  {
    "caption": "(E) YAP  occupancy at the ROR1  enhancer as determined by ChIP-qPCR. The known YAP  targets, CTGF  and CYR61  promoters, were tested as positive controls, and ROR1   intron 1 and AFM   promoter were tested as negative controls (n = 4, biological replicates).",
    "ncbi_link": "AFM: 173
CYR61: 3491
CTGF: 1490
ROR1: 4919"
  },
  {
    "caption": "(G)  Western blot  analysis of YAP, TAZ, ROR1, and β-actin in S2-VP10  cells transfected with control or YAP1/WWTR1  siRNA.",
    "ncbi_link": "WWTR1: 25937
YAP1: 10413"
  },
  {
    "caption": "(I) Relative expression  of ROR1  and YAP   target genes (CTGF  and CYR61) in S2-VP10  cells treated with DMSO  or verteporfin  (VP) (n = 3, biological replicates). mRNA levels are normalized to that of RPS18.",
    "ncbi_link": "CYR61: 3491
CTGF: 1490
ROR1: 4919
RPS18: 6222"
  },
  {
    "caption": "(O), Treatment of PDO#1 and S2-VP10 organoids  with DMSO  or JQ1  (n = 3, biological replicates). Relative expression  of ROR1  (O), mRNA levels are normalized to that of RPS18. Data information: Data are presented as mean ± s.e.m., *, p < 0.05. ; two-sided t-test (O)",
    "ncbi_link": "ROR1: 4919
RPS18: 6222"
  },
  {
    "caption": "E, F Co‐immunoprecipitation of endogenous TBC1D5 and ATG9A with myc‐VPS29(E) transiently overexpressed in 293T cells or with HA‐Flag‐VPS35 (F) transiently overexpressed in 293T cells, treated with DMSO or KU0063794 (6 h).",
    "ncbi_link": "VPS29: 51699"
  },
  {
    "caption": "I Magnified still images extracted from Supplementary Movie S2. mCherry‐TBC1D5 co‐localizes with GFP‐ATG9 upon autophagy induction by mTOR inhibitor, KU0063794.",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "A Lysates of U2OS cells stably expressing control shRNA or shRNA targeting VPS29 or TBC1D5. Cells were treated with DMSO or KU0063794 (6 h), lysed in RIPA buffer (1% SDS) and lysates were subjected to SDS-PAGE.",
    "ncbi_link": "TBC1D5: 9779
VPS29: 51699"
  },
  {
    "caption": "B U2OS cells stably expressing mCherry‐ATG9 were depleted of VPS29 and TBC1D5 using shRNAs, treated with DMSO or KU0063794 (6 h), fixed with 2% PFA, and immunostained with anti‐LAMP1 antibody.",
    "ncbi_link": "TBC1D5: 9779
VPS29: 51699"
  },
  {
    "caption": "E Quantification of ATG9 and LAMP1 co−localization in cells stably depleted for TBC1D5 (shRNA#1) or VPS29 (shRNA#2), transiently transfected with myc−TBC1D5 plasmid resistant to TBC1D5 shRNA#1. Cells were treated with KU0063794 (6 h), 20 h post−transfection, fixed, and immunostained with anti−LAMP1 and anti−myc antibodies.",
    "ncbi_link": "TBC1D5: 9779"
  },
  {
    "caption": "F Control shRNA and U2OS cell lysates depleted for TBC1D5 (shRNA#1), transfected with empty plasmid or with shRNA‐resistant myc‐TBC1D5.",
    "ncbi_link": "TBC1D5: 9779"
  },
  {
    "caption": "G Immunofluorescence of TBC1D5 (shRNA#1) cells transiently transfected with shRNA‐resistant myc‐TBC1D5, treated with KU0063794 (6 h). 20 h post‐transfection cells were treated, subsequently fixed, and immunostained with anti‐myc and anti‐LAMP1 antibodies.",
    "ncbi_link": "TBC1D5: 9779"
  },
  {
    "caption": "B Control cells and TBC1D5 (shRNA#1) U2OS cell lysates subjected to SDS-PAGE, subsequently blotted with endogenous antibodies for AP2 subunits AP2A1 and AP2M1.",
    "ncbi_link": "TBC1D5: 9779"
  },
  {
    "caption": "C Immunofluorescent staining of AP2A1 in U2OS shRNA control, or shRNA#1 TBC1D5 cells treated with KU0063974 or DMSO (6 h).",
    "ncbi_link": "TBC1D5: 9779"
  },
  {
    "caption": "A U2OS cells stably expressing HA‐Flag‐ATG9A transfected with siRNA targeting AP2A1 (40 nM), or siRNA AllStar control (40 nM) were treated with KU0063794 or DMSO (6 h) 4 days post‐transfection, fixed, and stained with anti‐HA antibody.",
    "ncbi_link": "AP2A1: 160"
  },
  {
    "caption": "C Lysates of U2OS cells transfected with siRNA targeting AP2A1, or siRNA control AllStars analyzed by SDS-PAGE.",
    "ncbi_link": "AP2A1: 160"
  },
  {
    "caption": "D U2OS cells stably expressing mCherry−ATG9 were transiently transfected with GFP−Dynamin 2 or GFP−Dynamin 2 (K44A), 20 h post−transfection cells were fixed and with anti−TBC1D5 antibody. ATG9A and Dynamin 2co−localization is indicated by arrows.",
    "ncbi_link": "Dynamin 2: 1785"
  },
  {
    "caption": "Immunofluorescence and reporter expression in spheroids derived from single WT and Hdac3-/- naïve mESCs. DNA counterstain is Hoechst. Dashed white lines indicate the embryonic Gata6::mCherry negative part. Scale bar: 10 μm.",
    "ncbi_link": "Hdac3: 15183"
  },
  {
    "caption": "Nanog>GFP and Gata6::mCherry fluorescence intensities of WT and Hdac3-/- Fraction of Gata6::mCherry positive cells in indicated genotypes and conditions after 4d Jak(i) blocks LIF, LDN19 BMP4 and PD03 FGF signaling. Average and SD of at least two independent clones.",
    "ncbi_link": "Hdac3: 15183"
  },
  {
    "caption": "Scatter plots of log2 fold change (FC) gene expression changes (∆mRNA) between naïve Hdac3-/- or Dax1-/- mutants and WT mESCs (left), between Nanog>GFP-expressing Hdac3-/- or Dax1-/- mutants and WT cells (middle), and between Gata6::mCherry-expressing Hdac3-/- or Dax1-/- mutants and Nanog>GFP-expressing WT cells (right). Cluster 5 genes are colored and selected PrE TFs labeled.",
    "ncbi_link": "GFP: 
mCherry: 
Gata6: 14465
Hdac3: 15183
Nanog: 71950
Dax1: 11614"
  },
  {
    "caption": "Expression of PrE markers relative to Dax1-/- cells (B), and fraction of Gata6::mCherry positive cells after 3d in SLRA (C) in indicated genotypes. Average and SD of three independent clones.",
    "ncbi_link": "mCherry: 
Gata6: 14465
Dax1: 11614"
  },
  {
    "caption": "Genome-browser view of the Gata6 locus showing accessibility and chromatin mark changes in indicated mutants, and of ChIPseq signals of indicated TFs and H3K27ac in E6.5 VE and EPI. The grey area indicates enh-45.",
    "ncbi_link": "Gata6: 14465"
  },
  {
    "caption": "Confocal microscopy of YFP-ATG8e-labeled autophagic bodies in root cells of Col-0/YFP-ATG8e and VISP1OE/YFP-ATG8e plants. 7-day-old seedlings were inoculated in liquid ½MS medium with 1 µM ConA for 12 h in dark. Scale bar = 20 μm.   Puncta numbers of YFP-ATG8e-labeled autophagic bodies per 10 cells in panel A. Data points represent means of three biological repeats. Error bars indicate SD. ***p < 0.001 (Student's t-test).   ",
    "ncbi_link": "YFP: 
ATG8e: 819125"
  },
  {
    "caption": "Long-term symptoms of Col-0, VISP1OE1, VISP1OE2, rdr6-15, and sgs3-1 plants inoculated with CMV-2blm at 50 dpi. Scale bar = 2 cm.",
    "ncbi_link": "rdr6: 824112
sgs3: 832422"
  },
  {
    "caption": "Northern blotting analyzing accumulation of genomic RNAs (gRNAs) in systemically leaves of Col-0, OE1 (VISP1OE1), OE2 (VISP1OE2), rdr6-15, and sgs3-1 plants infected by CMV-2blm at 14 dpi. Methylene blue-stained rRNA were used as loading controls.   Northern blotting analyzing accumulation of RNA3-derived   vsiRNAs in the same samples as shown in panel D.",
    "ncbi_link": "rdr6: 824112
sgs3: 832422"
  },
  {
    "caption": "Long-term systemic symptoms of Col-0, visp1-1, visp1-2, rdr6-15, and sgs3-1 plants inoculated with CMV-2blm at 50 dpi. Scale bar = 2 cm.",
    "ncbi_link": "rdr6: 824112
sgs3: 832422"
  },
  {
    "caption": "Confocal analysis of effect of VISP1-Flag VISP1mARM-Flag, and VISP1mUIM-Flag on RDR6-YN and SGS3-YC formed bodies in N. benthamiana leaves at 60 hpi. EV: empty vector. Scale bar = 20 μm.   Numbers of RDR6-YN and SGS3-YC formed bodies per 10 cells in E were used for quantification. Data points represent means of three biological repeats. Error bars indicate SD. Letters indicate significant differences (ANOVA, P < 0.05).   ",
    "ncbi_link": "Flag: "
  },
  {
    "caption": "Western blotting detecting accumulation of the endogenous SGS3 protein in leaves of 2-week-old Col-0, VISP1OE, visp1, and sgs3-1 Arabidopsis plants with anti-SGS3 antibodies.   Western blotting detecting accumulation of the endogenous SGS3 protein in leaves of 2-week-old Col-0, VISP1OE, VISP1mUIM/OE, and VISP1mARM/OE Arabidopsis plants.   Western blotting detecting accumulation of the endogenous SGS3 protein in 2-week-old VISP1-overexpressing Col-0, atg5-1, and atg7-1 mutants.   ",
    "ncbi_link": "atg5: 831594
atg7: 834630
sgs3: 832422"
  },
  {
    "caption": "Developmental phenotypes of rosette leaves of 5-week-old Col-0, visp1-1, visp1-2, VISP1OE1, VISP1OE2, and sgs3-1 seedlings. Arrowheads indicate the 8th and 9th rosette leaves from the top leaves. Scale bar = 2 cm.   The length/width ratios of the 8th and 9th rosette leaves of the seedlings shown in A. Every dot represents data from the length/width ratio of one leave (n = 20). Letters indicate significant   differences (ANOVA, P < 0.05).",
    "ncbi_link": "sgs3: 832422"
  },
  {
    "caption": "Northern blotting detecting accumulation of TAS1-TasiR255, TAS2-TasiR1511, TAS3-TasiR5′D8, miR173, and miR390 in leaves of Arabidopsis plants shown in panel A. Values represent relative accumulation (RA) of siRNAs and values in Col-0 plants were set as 1. rRNA served as loading controls.",
    "ncbi_link": "miR173: 
miR390: 
TAS1: 
TasiR1511: 
TasiR255: 
TasiR5′D8: 
TAS2: 3768418
TAS3: 3768766"
  },
  {
    "caption": "(E) Mrp17 variants rescue ∆mrp17 strain growth defect on respiratory media: the indicated variants or empty vector (EV) were introduced in WT yeast and then the genomic MRP17 was disrupted by knock out, the resulting mutants were serially diluted 10× and spotted on media containing glucose or glycerol as a sole carbon source.",
    "ncbi_link": "MRP17: 853867
Mrp17: 853867
mrp17: 853867"
  },
  {
    "caption": "(A) The in vitro import of Mrp17-DHFRmut is sensitive to the elimination of outer mitochondrial membrane proteins by trypsinization (left), more so than the model import substrate Atp1 (right). Mitochondria were incubated with the indicated concentrations of trypsin and the import assay was performed as described in the legend for Fig. 2. Proteinase K (PK) was not added to the sample without mitochondria. (B) In vitro translocation of Mrp17-DHFRmut into mitochondria isolated from WT and ∆tom20 yeast showing reduced translocation in ∆tom20 background.",
    "ncbi_link": "tom20: 852973"
  },
  {
    "caption": "(G),(H) Import of Mrp17-DHFRmut and control proteins Atp1 and Aac1 into WT, tim17-ts (G) and tim22-ts (H) mitochondria. Import was performed at indicated temperatures, proteinase K was added to all samples except the loading control in the first lane of each autoradiograph (20% of protein amount used for each import reaction). The full autoradiograph for Aac1 with molecular weight markers is shown in Appendix Figure S6D.",
    "ncbi_link": "tim17: 853298
tim22: 851309"
  },
  {
    "caption": "(b) Coimmuno-precipitation (IP) of Fbxo7-HA and Flag-Parkin in whole-cell lysates from U2OS cells over-expressing both proteins. IB, immunoblot. Molecular mass markers are in kilodaltons.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(c) Coimmunoprecipitation of endogenous Fbxo7 with Flag-Parkin in HEK293T cells transfected with Flag-Parkin or a control protein (EGFP).",
    "ncbi_link": "Parkin: O60260///5071"
  },
  {
    "caption": "(d) Flag immunoprecipitation was repeated in U2OS cells transfected with Flag-Parkin and either full-length (1-522) T7-Fbxo7 or an N-terminal truncation lacking the Ubl domain (89-522).",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(e) As in d, using lysates from U2OS cells expressing Flag-Parkin and T7-Fbxo7, either full length (1-522) or a C-terminal deletion of the proline-rich region (1-398). * indicates IgG heavy chain.",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(f) In vitro-translated Flag-Parkin was incubated with bacterially expressed GST or GST fused to the Fbxo7 Ubl domain (1-88) immobilized on glutathione beads. Bead-bound proteins and inputs were analyzed by immunoblotting with anti-Parkin antibodies.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(g) The disease-causing mutation T22M interferes with Fbxo7's interaction with Parkin. Coimmunoprecipitation was performed as in b using lysates from U2OS cells expressing Flag-Parkin and WT or T22M Fbxo7-HA.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(h) Coimmunoprecipitation of Flag-Parkin and Fbxo7 in the mitochondrial and cytosolic fractions of HEK293T cells overexpressing both proteins. CxVα and GAPDH are markers for mitochondria and cytoplasm, respectively. All western blots are representative of experiments performed at least three times. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(b) Fbxo7 levels are increased in Flag-Parkin complexes immunoprecipitated (IP) from the mitochondrial fraction of HEK293T cells transfected with Flag-Parkin and untagged Fbxo7 following 1 or 3 h treatment with CCCP (10 µM).",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(c) Parkin localization at the mitochondria was assessed by immunocytochemistry in SH-SY5Y cells transfected with Flag-Parkin plus scrambled (scr) or Fbxo7 siRNA, following 1 or 3 h treatment with CCCP (10 μM). Cells were scored visually for the colocalization of Flag-Parkin with HtrA2, a mitochondrial marker. Images are displayed for cells transfected as indicated, following 0 or 3 h CCCP treatment. For corresponding images at 1 h treatment, see Supplementary Figure 2c. Nuclei (blue) were stained with DAPI. Scale bars, 10 μm.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(d) Loss of Flag-Parkin translocation upon Fbxo7 silencing is rescued by WT and R378G Fbxo7, but not by T22M Fbxo7, by R498X Fbxo7 or by Fbxo7 in which the mitochondrial targeting sequence is mutated (mt-MTS). For c,d, histograms indicate the percentage of cells in which Parkin localized to the mitochondria. Data are presented as mean of three experiments ± s.e.m. *P 0.05, **P 0.01 compared to cells transfected with Flag-Parkin plus Fbxo7 siRNA.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(e) T7-tagged WT Fbxo7 localizes to both cytosolic (C) and mitochondrial (M) fractions of transfected HEK293T cells, but MTS mutant (mt-MTS) Fbxo7 localizes only to the cytosolic fraction. CxVα and PDHE1α are mitochondrial markers; GAPDH is a cytosolic marker. All western blots are representative of experiments performed at least three times. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(a,b) Overexpression of Fbxo7 by da-GAL4 (da>Fbxo7) suppresses climbing (a) and flight (b) defects of parkin mutants.",
    "ncbi_link": "GAL4: 
da: 34413
Fbxo7: 38443
parkin: 40336"
  },
  {
    "caption": "(c) Overexpression of Fbxo7 also suppresses dopaminergic (DA) neurodegeneration parkin mutants.",
    "ncbi_link": "Fbxo7: 38443
parkin: 40336"
  },
  {
    "caption": "(d-f) Top and middle panels, toluidine blue-stained sections of adult thorax. Bottom panels, transmission electron micrographs of muscle. Fbxo7 overexpression suppresses muscle degeneration and mitochondrial disruption in parkin mutants. Scale bars: 200 μm (top), 20 μm (middle), 2 μm (bottom). Images are representative of three animals per genotype.",
    "ncbi_link": "Fbxo7: 38443
parkin: 40336"
  },
  {
    "caption": "(g,h) Overexpression of Fbxo7 pathogenic mutants, mt-MTS or isoform 2 by da-GAL4 fails to rescue climbing (g) and flight (h) deficits in parkin mutants. Control genotype is park25/+; da-GAL4/+. All transgenic lines are site-directed integration except WT(4), which is random integration line 4 (see Supplementary Fig. 3 and Online Methods). Histograms indicate mean ± s.e.m. One-way ANOVA with Bonferroni correction (***P 0.001, **P 0.01). For climbing and flight assays, at least 50 flies were assessed; number of flies is shown for each bar.",
    "ncbi_link": "GAL4: 
da: 34413
Fbxo7: 38443
parkin: 40336"
  },
  {
    "caption": "(a) Coimmunoprecipitation (IP) of PINK1-Myc and Flag-Fbxo7 in whole-cell lysates from U2OS cells overexpressing both proteins. IB, immunoblot.",
    "ncbi_link": "Fbxo7: 25793
PINK1: 65018"
  },
  {
    "caption": "(b) Coimmunoprecipitation of PINK1-Myc with full-length and two N-terminally deleted Flag-Fbxo7 forms. PINK1-Myc is detected at low levels in complex with Flag-Fbxo7(89-522) but not with Flag-Fbxo7(129-522).",
    "ncbi_link": "Fbxo7: 25793
PINK1: 65018"
  },
  {
    "caption": "(c) As in b, using lysates from U2OS cells expressing PINK1-Myc, and Flag-Fbxo7 containing either N- or C-terminal truncations.",
    "ncbi_link": "Fbxo7: 25793
PINK1: 65018"
  },
  {
    "caption": "(d) In vitro coprecipitation experiments were performed using in vitro-translated (IVT) PINK1-Myc and either GST or GST fusions of Fbxo7(1-398) or Fbxo7(129-398) immobilized on glutathione beads.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(e) Competitive binding assays using immobilized GST-Fbxo7(1-398) incubated with IVT Flag-Parkin and/or full length (top panel) or N-terminally truncated (bottom panel) PINK1-Myc. Input and bead-bound proteins were analyzed by immunoblotting as indicated.",
    "ncbi_link": "Fbxo7: 25793
PINK1: 65018"
  },
  {
    "caption": "(f) As in e, immobilized GST-ΔN-PINK1 (top panel), GST-Parkin (middle panel) and immobilized GST alone (bottom panel) were incubated with combinations of IVT Flag-Parkin, T7-ΔN-PINK1 and Fbxo7-HA as indicated. Input and bead-bound proteins were analyzed by immunoblotting with the indicated antibodies. All western blots were performed a minimum of three times. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "Parkin: 5071
PINK1: 65018"
  },
  {
    "caption": "(a) PINK1 localization at the mitochondria was assessed by immunocytochemistry in SH-SY5Y cells transfected with PINK1-HA plus scrambled (scr) or Fbxo7 siRNA following 1 or 3 h treatment with CCCP (10 μM). Cells were scored visually for the colocalization of PINK1-HA with complex Vβ subunit (CxVβ), a mitochondrial marker. Nuclei (blue) are stained with DAPI. Histograms indicate the percentage of cells in which PINK1-HA accumulated at the mitochondria. Data are presented as mean ± s.e.m.; *P 0.05. Representative images are displayed for cells transfected as indicated, following 0 or 3 h CCCP treatment. For corresponding images at 0 h and 1 h treatment, see Supplementary Figure 5a. Scale bars, 10 μm.",
    "ncbi_link": "Fbxo7: 25793
PINK1: 65018"
  },
  {
    "caption": "(b) Fbxo7 accumulation in the mitochondrial fraction following treatment with CCCP (10 μM) is impaired in SH-SY5Y cells transfected with PINK1 siRNA compared to scrambled siRNA (scr). IB, immunoblot. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(c-f) Overexpression of Fbxo7 does not rescue climbing (c,e) or flight (d,f) defects in PINK1 male mutants (PINK1B9) or PINK1:parkin double mutants (PINK1B9;park25, daG4). Control genotypes are PINK1B9/+; da-GAL4/+ (c,d) and da-GAL4/+ (e,f). Histograms indicate mean ± s.e.m. One-way ANOVA with Bonferroni correction (***P 0.001). For climbing and flight assays, at least 50 flies were assessed; number of flies is shown for each bar for c-f.",
    "ncbi_link": "GAL4: 
da: 34413
Fbxo7: 25793
parkin: 50873
PINK1: 65018"
  },
  {
    "caption": "(a,b) Ubiquitination of Mfn1 following treatment with CCCP (10 μM) is reduced in the mitochondrial fraction of both SH-SY5Y cells stably expressing Fbxo7 short hairpin RNA (Fbxo7 KD) compared to an empty vector control line (a) and in patient fibroblasts with homozygous R378G mutation compared to fibroblasts from healthy controls (b). Arrowheads indicate ubiquitinated Mfn1. IB, immunoblot.",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(c,d) Fbxo7 expression restores elevated Mfn steady-state levels in parkin (c) but not PINK1 (d) mutant Drosophila. Histograms show mean ± s.e.m. of densitometry analysis of Mfn immunoblots above, normalized to complex Vα (CxVα). Control genotypes are park25/+; da-GAL4/+ (c) and PINK1B9/+; da-GAL4/+ (d).",
    "ncbi_link": "GAL4: 
da: 34413
Fbxo7: 38443
parkin: 40336
PINK1: 31607"
  },
  {
    "caption": "(e) Mitochondria in control Drosophila S2R+ cells stained with MitoTracker Red show a heterogeneous morphology, with a mixture of tubules and fragmented mitochondria. RNAi knockdown of parkin or PINK1 causes excessive fusion and elongated mitochondria compared to control double-stranded RNA (Caenorhabditis elegans gene ZK686.3). Expression of Fbxo7 restores parkin but not PINK1 knockdown phenotype to WT appearance. Scale bar shows 5 μm. (f) Quantification of mitochondrial morphology in dsRNA treated cells. Scoring system: 1, fragmented; 2, WT; 3, tubular; 4, hyper-fused (clumped). Histograms indicate mean ± s.e.m. Two-tailed Student t-tests (***P 0.001, *P 0.05). All western blots were performed a minimum of three times and images are representative of 100 cells scored per condition. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "Fbxo7: 38443
parkin: 40336
PINK1: 31607
ZK686.3: 176089"
  },
  {
    "caption": "(a) Treatment with CCCP (10 μM) results in an increase in LC3-II in the mitochondrial but not the cytosolic fraction of cells stably expressing the empty shRNA vector (control), and this is delayed in stable Fbxo7 knockdown (KD) SH-SY5Y cells.",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(c) Mitochondrial accumulation of p62 following CCCP treatment is inhibited by Fbxo7 siRNA. Flag-Parkin overexpressing SH-SY5Y cells were transfected with scrambled (scr) or Fbxo7 siRNA as indicated and treated with either DMSO or CCCP (10 μM) for 6 h. Colocalization of p62 with HtrA2, a mitochondrial marker, was assessed by Pearson's correlation coefficient (Rr) on a cell-by-cell basis. Histogram shows the percentage of cells in which Rr was greater than 0.5. Data are represented as mean ± s.e.m., *P 0.05. Scale bars, 10 μm.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "(d) Mitophagy was analyzed in untransfected (UT) SH-SY5Y cells or in stable Flag-Parkin overexpressing SH-SY5Y cells transfected with either scrambled (scr) or Fbxo7 siRNA. Histogram indicates the percentage of cells with no remaining mitochondria following 24 h treatment with CCCP (10 μM) for each condition. Complex Vβ subunit (CxVβ) was used as a mitochondrial marker. Data are presented as mean ± s.e.m., **P 0.01. Scale bars, 10 μm.",
    "ncbi_link": "Fbxo7: 25793"
  },
  {
    "caption": "(e) Mitochondrial mass was measured in Flag-Parkin overexpressing SH-SY5Y cells transfected with scrambled (scr) or Fbxo7 siRNA and treated for 24 h with either dimethylsulfoxide (DMSO) vehicle or CCCP (10 μM). For representative images, see Supplementary Figure 8d. Full-length blots are presented in Supplementary Figure 9.",
    "ncbi_link": "Fbxo7: 25793
Parkin: 5071"
  },
  {
    "caption": "Western blot analysis of nuclear extracts of ring (R), trophozoite (T), and schizont (S) stages from a synchronous population of SMC3-3HA-glmS parasites. SMC3-3HA is detected with an anti-HA antibody. An antibody against histone H3 is used as a control. Molecular weights are shown to the right. SMC3-3HA has a predicted molecular weight of 147.3 kDa (of which 3.3 kDa correspond to the 3HA tag).",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569"
  },
  {
    "caption": "(C) Immunofluorescence assays of fixed RBCs infected with trophozoite or schizont stage SMC3-3HA-glmS parasites. DNA was stained with DAPI (blue) and SMC3-3HA was detected with anti-HA (green in B and magenta in C) antibody. HP1 was detected with anti-HP1 antibody (green in C). DIC, differential interference contrast. Scale bars equal 10 µm (B) and 5 µm (C).",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569"
  },
  {
    "caption": "Western blot analysis of nuclear extracts at 12, 24, and 36 hpi from a clonal population of SMC3-3HA-glmS parasites in the absence (-) or presence (+) of glucosamine (GlcN). SMC3-3HA is detected with an anti-HA antibody. An antibody against histone H3 is used as a control. Molecular weights are shown to the right.",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569"
  },
  {
    "caption": "Growth curve showing parasite growth rate (parasitemia at Day X/parasitemia at Day 1) over five days for WT and two clones of SMC3-3HA-glmS parasites in the absence or presence of glucosamine (GlcN). Glucosamine treatment was started 96 h (two IDC cycles) before Day 1 to ensure SMC3 knockdown during the days sampled Uninfected red blood cells (Blood) served as reference of background. Error bars indicate standard deviation of three technical replicates (n = 3). A two-way ANOVA with Tukey post hoc test was used for statistical analysis. No significant differences were found.",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569"
  },
  {
    "caption": "RNA-seq of an SMC3-3HA-glmS clone shows smc3 transcript levels (FPKM) at 12 (blue, q = 8.5 x 10-3), 24 (coral, q = 1.3 x 10-39), and 36 (green, q = 4.1 x 10-54) hpi in the absence (filled circles) or presence (empty circles) of glucosamine (GlcN). Error bars represent standard deviation of three technical replicates except for the untreated 12 hpi parasites, for which there were two replicates. P-values are calculated with a Wald test for significance of coefficients in a negative binomial generalized linear model as implemented in DESeq2 q = Bonferroni corrected P-value. Asterisks indicate q values < 0.5.",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569
smc3: 812569"
  },
  {
    "caption": "ChIP-seq data showing enrichment of SMC3 (y-axis = ChIP/Input) at 12 (blue), 24 (coral), and 36 (green) hpi in clonal SMC3-3HA-glmS parasites at the rhoptry-associated protein 2 (rap2, PF3D7_0501600) and the glideosome-associated protein 45 (gap45, PF3D7_1222700) gene loci. The x-axis is DNA sequence, with the gene represented by a black box with white arrowheads to indicate transcription direction. One replicate (clone A) was used for ChIP-seq. ATAC-seq data from closely corresponding time points (15, 25, and 35 hpi) are shown in grey, with the y-axis representing ATAC-seq (RPM)/gDNA (RPM).",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569
PF3D7_0501600: 812869
rap2: 812869
rhoptry-associated protein 2: 812869
gap45: 811270
glideosome-associated protein 45: 811270
PF3D7_1222700: 811270"
  },
  {
    "caption": "RNA-seq of an SMC3-3HA-glmS clone shows transcript levels (FPKM) for rap2 (PF3D7_0501600) at 12 (q = 3 x 10-2) and 24 (q = 3.3 x 10-2) hpi and gap45 (PF3D7_1222700) at 12 (q = 8 x 10-1) and 24 (q = 1.6 x 10-2) hpi in the absence (black) or presence (grey) of glucosamine (GlcN). Error bars represent standard deviation of three technical replicates except for the untreated 12 hpi parasites, for which there were two replicates. P-values are calculated with a Wald test for significance of coefficients in a negative binomial generalized linear model as implemented in DESeq2 (Love et al, 2014). q = Bonferroni corrected P-value.",
    "ncbi_link": "HA: 
glmS: 938736
SMC3: 812569
PF3D7_0501600: 812869
rap2: 812869
gap45: 811270
PF3D7_1222700: 811270"
  },
  {
    "caption": "Expression values of rap2 (PF3D7_0501600) and gap45 (PF3D7_1222700) genes across the IDC (indicated on the x-axis by hpi) from the transcriptomics time course Data corresponding to 12 (blue), 24 (coral), and 36 (green) hpi time points are highlighted.",
    "ncbi_link": "PF3D7_0501600: 812869
rap2: 812869
gap45: 811270
PF3D7_1222700: 811270"
  },
  {
    "caption": "Full-length TLN (but not APP) accumulates in a distinct compartment in PS1−/−hippocampal neurons. Double-immunofluorescence staining for endogenous TLN (green, B36.1) and APP (red, mAb C1 6.1) in wild-type (top) and PS1−/− (bottom) hippocampal neurons (15-d culture). The inset shows an overview of the neuron. In wild-type neurons TLN labeling is essentially localized to the somatodendritic plasmalemma in contrast to APP, which is found in intracellular compartments. In addition, PS1 deficiency causes TLN, but not APP, to cluster in large somatic accumulations. Bars, 10 μm.",
    "ncbi_link": "PS1: 19164"
  },
  {
    "caption": "(A) Western blot analysis of endogenous TLN and APP in wild-type and PS1−/− hippocampal neurons. PS1 deficiency results in the accumulation of APP-CTF. No TLN-CTF (estimated ± 7 kD) was detected, neither was it detected after SFV-induced exogenous overexpression. Also, overexpression of a TLNΔE fragment did not generate a PS1-dependent TLN intracellular domain.",
    "ncbi_link": "TLN: 15898
PS1: 19164"
  },
  {
    "caption": "(B) Different constructs fused to the Gal4VP16 domain were used in a γ-secretase reporter assay. Control transfections (pIPspAdApt empty vector and pIPspAdApt-APP without Gal4VP16) show no luciferase activity. APP-Gal4VP16 and NotchΔE-Gal4VP16 activate the luciferase gene upon cleavage and are inhibited by DAPT, L658,458, or compound 32 (125 nM). No luciferase activity was detected using TLNΔE or APP in which the transmembrane domain was replaced by that of TLN (APP/TLNTMR chimaera), indicating that this region is not cleaved by γ-secretase.",
    "ncbi_link": "APP: 351
TLN: 7087
Notch: 4855///4854///4853///4851"
  },
  {
    "caption": "(D) Adenoviral reintroduction of human PS1 suppresses TLN accumulations. 30-35% of PS1−/− neurons display TLN accumulations, in contrast to <5% in PS1+/+ and +/− cultures as well as in cultures expressing human PS1 in a PS1−/− background. However, suppression of TLN accumulations was obtained by adenoviral introduction of human PS1. A clear dose-dependent inhibition was seen with increasing MOI of adenoviral (AV) human PS1, but also the familial Alzheimer's disease-linked PS1G384A and dominant-negative PS1D257A mutants. Control adenoviral infections with eGFP did not have a significant effect. After 9-11 d post-infection (15 d post-plating), neurons displayed significant PS1 protein expression as demonstrated by double staining for TLN and human PS1(mAb 5.2). Bars, 20 μm.",
    "ncbi_link": "PS1: 5663"
  },
  {
    "caption": "Wild-type and PS1−/− cortical neurons were transduced with SFV-TLN (A) or -APP (B), pulse labeled for 15 min with [35S]methionine, and chased for different time periods. ImmunoprecipitatedTLN and APP were treated with EndoH and analyzed by SDS-PAGE and phosphorimaging. The accumulation of an EndoH-resistant band indicates progressive maturation during Golgi passage; however, the ratio of EndoH-resistant to -sensitive TLN (A, top) and APP (B, top) revealed no difference (mean ± SEM, n = 3). Instead, the half-life of overexpressed TLN (A, bottom), but not full-length APP (B, bottom), is significantly prolonged in neurons−/−neurons (mean ± SEM, n = 3).",
    "ncbi_link": "APP: 351
TLN: 15898
PS1: 5663"
  },
  {
    "caption": "(C) Wild-type and PS1−/− hippocampal neurons (12 d) were scraped, pelleted, and treated with 10 mU EndoH, followed by Western blot detection of APP, TLN, PS1, nicastrin (NCT), synaptophysin, and ductin. TLN levels are increased almost fourfold in PS1−/− neurons. No EndoH-sensitive TLN was detected in PS1−/− neurons, indicating a complete maturation. APP-CTF shows a dramatic accumulation (44-fold; mean ± SEM, n = 3).",
    "ncbi_link": "PS1: 19164"
  },
  {
    "caption": "(B and C) Double immunostaining of wild-type and PS1−/− hippocampal neurons for TLN (green) and autophagic vacuole-associated Apg12p (B) and LC3 (C). To detect both sets of pAbs, an alternative method was developed using biotinylated anti-TLN (see Materials and methods). Each experiment included controls for specificity (not depicted). In wild-type neurons, both Apg12p and LC3 (B and C, top row) were broadly distributed in cell bodies and neurites, but did not colocalize with TLN. Colocalization was only observed in multiple TLN accumulations in PS1−/− hippocampal neurons (second row in B and C, respectively). For Apg12p, coimmunostaining was also noticed in small discrete structures in the proximal dendrites (B, bottom row). Bars, 10 μm.",
    "ncbi_link": "PS1: 19164"
  },
  {
    "caption": "(A) Intracellular sorting and maturation of catD. Wild-type and PS1−/− neurons were metabolically labeled and chased for the indicated time periods. Phosphorimaging of immunoprecipitated radiolabeled catD did not reveal a difference in the ratio of proteolytically processed 46-kD intermediate vs. 52-kD precursor (mean ± SEM, n = 3).",
    "ncbi_link": "PS1: 19164"
  },
  {
    "caption": "(B-D) TLN localizes to autophagic vacuoles of catD−/−hippocampal neurons. Lysotracker staining revealed sparsely distributed small-sized organelles in wild-type and PS1−/− neurons in contrast to catD−/−neurons where high numbers of large Lysotracker-positive organelles were found (B, arrowheads). Although TLN accumulations in PS1−/− were fully negative for Lysotracker, some acidic organelles tended to closely associate (C, arrowheads, middle). In catD−/− neurons, TLN was clearly detected in the large acidic organelles (C, bottom). Bars, 20 μm. (D) At the immuno-EM level, the large acidic organelles seen in catD−/−neurons represent dense autophagic vacuole-like structures (star) that label positive for TLN (10-nm gold). M, mitochondrion. Bars, 200 nm.",
    "ncbi_link": "catD: 13033
PS1: 19164"
  },
  {
    "caption": " B, C. Effects of deleting β′ ZBD on transcriptional activities of RNAP on different promoters. The fliCp (B) was used as template for σ28-dependent transcription, and the lacUV5p (C) was used in σ70-dependent transcription. RNA products indicated by solid triangles were quantified and the signal obtained from 100 nM wild-type RNAP was normalized to 1 in each test respectively. ",
    "ncbi_link": "fliCp: 949101
lacUV5p: 945006"
  },
  {
    "caption": " D. Transcriptional activities of ZBD mutated σ28-RNAP on fliCp. RNA products indicated by solid triangles were quantified. ",
    "ncbi_link": "fliCp: 949101"
  },
  {
    "caption": " E. Binding of σ28-RNAP with fliCp as detected by EMSA (left). The heparin-resistant RNAP-promoter open complex is indicated as \"RPo\", and the heparin-sensitive RNAP-promoter closed complex is shown as \"RPc\". Percentages of RNAP-promoter open complex (RPo) and closed complex (RPc) in EMSA performed using σ28-RNAP and fliCp (right). ",
    "ncbi_link": "fliCp: 949101"
  },
  {
    "caption": " F. DNase I footprinting of the fliCp complex with σ28-RNAP. Promoter DNA was labeled on the non-template strand. The promoter region protected by RNAP is indicated by a red box at the bottom panel. ",
    "ncbi_link": "fliCp: 949101"
  },
  {
    "caption": " B, C. Promoter activities of tarp (B) and fliCp (C) in E. coli wild-type (Ec-WT) and its mutants expressing ZBD-mutated RNAP (Ec-K74A, Ec-K87A and Ec-K74A-K87A) shown as mean ± SD from three replicates. ",
    "ncbi_link": "fliCp: 949101
tarp: 946399"
  },
  {
    "caption": " E. Relative mRNA levels of flagellar genes in Ec-K74A-K87A strain comparing with that in Ec-WT (normalized to 1 for each gene). Diagram for the role of σ28 (fliA gene) in flagella regulon hierarchy Clarke & Sperandio, 2005Fitzgerald, 2014(; ) is shown in the left panel. Data are mean ± SEM from three replicates. ",
    "ncbi_link": "fliA: 948824"
  },
  {
    "caption": "F. Motilities of Ec-K74A-K87A strains with over-expression of wild-type rpoC gene (Ec-K74A-K87A-C) or carrying the control plasmid (Ec-K74A-K87A-V).",
    "ncbi_link": "rpoC: 948487"
  },
  {
    "caption": " G. Activities of fliCp in Ec-K74A-K87A-C and Ec-K74A-K87A-V strains. L-arabinose was used at final concentration of 0.002%. Data are mean ± SD from three colonies. ",
    "ncbi_link": "fliCp: 949101"
  },
  {
    "caption": " B. Activities of chimeric σ28-R4m in initiating transcription from tarp-35m, when reconstituted with wild-type (WT) or ZBD mutated RNAP core enzyme. ",
    "ncbi_link": "tarp: 946399"
  },
  {
    "caption": " Effects of mutating β′ ZBD on transcriptional activities of σ38-RNAP on osmYp. ",
    "ncbi_link": "osmYp: 948895"
  },
  {
    "caption": " Effects of mutating β′ ZBD on transcriptional activities of σ38-RNAP on osmYp. ",
    "ncbi_link": "osmYp: 948895"
  },
  {
    "caption": " Effects of mutating β′ ZBD on transcriptional activities of σ70-RNAP on osmYp. ",
    "ncbi_link": "osmYp: 948895"
  },
  {
    "caption": "A-CConfirmation by mass spectrometry that Rab8A (A), Rab8B (B) and Rab13 (C) Ser111 is phosphorylated upon PINK1 activation after CCCP treatment. Flp‐In T‐Rex HEK293 cells expressing empty‐FLAG, WT PINK1‐FLAG and KI (D384A) PINK1‐FLAG were transfected either with HA‐Rab8A (A), HA‐Rab8B (B) or HA‐Rab13 (C) induced with doxycycline and stimulated with 10 μM of CCCP for 3 h. Whole‐cell lysates (10 mg) were immunoprecipitated with anti‐HA agarose, resolved by SDS-PAGE and stained with colloidal Coomassie blue (second panel). Coomassie‐stained bands migrating with expected molecular mass of HA‐Rabs were excised, in‐gel digested with trypsin and subjected to high‐performance liquid chromatography with LC‐MS/MS on an LTQ‐Orbitrap mass spectrometer. Upper panel shows the extracted ion chromatogram (XIC) analysis of Ser111‐containing phosphopeptides (8A, NIEEHApSADVEK; 8B, NIEEHApSSDVER; 13, SIKENApSAGVER) with the combined signal intensity of the 2+ and 3+ forms of the peptide indicated on the y‐axis. Note that the Ser111 phosphopeptide was only detected in samples from WT PINK1‐FLAG‐expressing cells following CCCP stimulation.",
    "ncbi_link": "PINK1: 65018
Rab13: 5872
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "DCharacterisation of Rab8A, Rab8B and Rab13 phospho‐Ser111 antibodies. Flp‐In T‐Rex HEK293 cells expressing empty‐FLAG, WT PINK1‐FLAG and KI (D384A) PINK1‐FLAG were transfected with either WT or Ser111Ala‐mutant (S111A) HA‐Rab8A, HA‐Rab8B or HA‐Rab13, induced with doxycycline and stimulated with 10 μM of CCCP for 3 h. Whole‐cell lysates (0.25 mg) were immunoprecipitated with anti‐HA agarose and immunoblotted with Rab8A, Rab8B or Rab13 phospho‐Ser111 antibodies. Part of the immunoprecipitates was used to immunoblot for HA antibody as loading controls.",
    "ncbi_link": "PINK1: 65018
Rab13: 5872
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "PINK1 is essential for CCCP‐mediated Rab8A Ser111 phosphorylation. WT and PINK1 KO HeLa cells were transfected with either WT or Ser111Ala (S111A) mutant constructs of HA‐Rab8A, HA‐Rab8B or HA‐Rab13. Some PINK1 KO HeLa cells were reintroduced with PINK1 by transfection of WT PINK1‐3xFLAG or KI (D384A) PINK1‐3xFLAG as indicated. After transfection for at least 24 h, cells were treated with DMSO as a vehicle control or CCCP for 20 h. Whole‐cell lysates (1 mg) were immunoprecipitated with anti‐HA agarose and immunoblotted with Rab8A, Rab8B or Rab13 phospho‐Ser111 antibody. Part of the immunoprecipitates was used to immunoblot for HA antibody as loading controls. For the lower panel, whole‐cell lysates (30 μg) were immunoblotted with total PINK1 antibody to confirm PINK1 expression and with GAPDH as loading controls.",
    "ncbi_link": "PINK1: 65018
Rab13: 5872
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "Endogenous Rab8A Ser111 phosphorylation is PINK1 dependent. WT and PINK1 KO HeLa cells were treated with DMSO as a vehicle control or CCCP for 20 h. Some PINK1 KO HeLa cells were reintroduced with PINK1 by transfection of WT PINK1‐3xFLAG or KI (D384A) PINK1‐3xFLAG as indicated for at least 24 h before CCCP treatment. Whole‐cell lysates (1 mg) were immunoprecipitated with anti‐Rab8A pre‐bound with protein A agarose followed by immunoblot with Rab8A phospho‐Ser111 antibody. Part of the immunoprecipitates was used to immunoblot with anti‐total Rab8A antibody as loading controls.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "Absence of Rab8A Ser111 phosphorylation in human mutant PINK1 patient fibroblasts. Primary skinfibroblasts were derived from a patient with homozygous PINK1 Q456X mutation or unaffected control. Cells were incubated with DMSO or CCCP for 20 h, and whole‐cell lysates (1 mg) were immunoprecipitated with anti‐Rab8A antibody conjugated to protein A agarose and immunoblotted with total or Rab8A phospho‐Ser111 antibody. Lysates (1 mg) were also subjected to immunoprecipitation with polyclonal anti‐PINK1 antibody and immunoblotted with monoclonal PINK1 antibody. Equal loading of protein extracts was confirmed by GAPDH.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "Absence of Rab8A Ser111 phosphorylation in PINK1 knockout MEFs. MEFs were derived from PINK1 knockout embryos or wild‐type controls (see Materials and Methods). Cells were incubated with DMSO or CCCP for 20 h, and whole‐cell lysates (1 mg) were immunoprecipitated with anti‐Rab8A antibody conjugated to protein A agarose and immunoblotted with total or Rab8A phospho‐Ser111 antibody. Lysates (1 mg) were also subjected to immunoprecipitation with a polyclonal anti‐mouse‐specific PINK1 antibody and immunoblotted with a different anti‐mouse‐specific PINK1 antibody. Equal loading of protein extracts was confirmed by GAPDH.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "Rab8A is not required for the activation of Parkin E3 ligase activity at mitochondria in response to PINK1 activation by CCCPWild‐type (WT) or Rab8A knockout (KO) HeLa cells were transfected with WT or Cys431Phe (C341F)‐mutant Parkin. After transfection for 24 h, cells were treated with DMSO as a vehicle control or 10 μM CCCP for 6 h. Mitochondrial enriched extracts (mitochondrial lysate) were incubated with ubiquitin‐binding resins derived from his‐halo‐ubiquilin1 UBA domain tetramer (UBAUBQLN1). Captured ubiquitylated proteins were subject to immunoblotting with anti‐CISD1 and anti‐mitofusin 2 antibodies. Mitochondrial lysate and total lysate were also subjected to immunoblotting with indicated antibodies for loading and protein expression controls. Phospho‐Ser111 Rab8A was detected after Rab8A immunoprecipitation from 200 μg of mitochondrial lysate with anti‐Rab8A antibody.",
    "ncbi_link": "Parkin: 5071
Rab8A: 4218"
  },
  {
    "caption": "In vitro phosphorylation analysis of Rab8A by PINK1. WT or S111A‐mutant Rab8A (1.2 μg) was incubated in the presence of MBP‐fused WT or KI (D359A) TcPINK1 (1.1 μg) and Mg2+‐[γ‐32P] ATP for the indicated time. Samples were subjected to SDS-PAGE, and proteins were detected by colloidal Coomassie blue staining (lower panel). The [γ‐32P] incorporation to substrate was detected by autoradiography (upper panel). Cerenkov counting was used to calculate the stoichiometry of substrate phosphorylation as mol of [γ‐32P] incorporation/mol of substrate. Ubiquitin was used as a positive control of the TcPINK1 substrate.",
    "ncbi_link": "PINK1: Q9BXM7///65018
Rab8A: 4218"
  },
  {
    "caption": "Time‐course comparison of PINK1‐mediated Rab8A, Rab8B and Rab13 Ser111 phosphorylation vs. Parkin Ser65 phosphorylation. Flp‐In T‐Rex HEK293 cells expressing WT PINK1‐FLAG were transfected with either WT or Ser111Ala‐(S111A) mutant HA‐Rab8A, HA‐Rab8B or HA‐Rab13, induced with doxycycline and stimulated with CCCP for the indicated time. In parallel, Flp‐In T‐Rex HEK293 cells expressing WT PINK1‐FLAG were transfected with either WT or Ser65 Ala (S65A)‐mutant Parkin. Whole‐cell lysates (0.25 mg) were immunoprecipitated with anti‐HA agarose and immunoblotted with indicated phospho‐Ser111 antibodies. Part of the immunoprecipitates was used to immunoblot for HA antibody as loading controls. For the lower panel, whole‐cell lysates (30 μg) were immunoblotted with indicated antibodies.",
    "ncbi_link": "Parkin: 5071
PINK1: 65018
Rab13: 5872
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "Time‐course comparison of endogenous PINK1‐mediated Rab8A, Rab8B and Rab13 Ser111 phosphorylation vs. Parkin Ser65 phosphorylation. HeLa cells were transfected with either WT or S111A‐mutant HA‐Rab8A, HA‐Rab8B or HA‐Rab13 for at least 24 h before CCCP treatment for the indicated time. Whole‐cell lysates (1 mg) were immunoprecipitated with anti‐HA agarose and immunoblotted with indicated phospho‐Ser111 antibodies. In parallel, HeLa cells were transfected with either WT or S65A‐mutant Parkin and whole‐cell lysates (30 μg) were immunoblotted with indicated antibodies.",
    "ncbi_link": "Parkin: 5071
Rab13: 5872
Rab8A: 4218
Rab8B: 51762"
  },
  {
    "caption": "Rabin8‐catalysed mant‐GDP release from mant‐GDP loaded WT, S111A and S111E mutants of Rab8A. The Rab proteins (1 μM) were incubated with 100 μM GDP in buffer (20 mM HEPES pH 7.5, 50 mM NaCl, 1 mM MgCl2, 2 mM DTE), and the reaction was started by the addition of 0.5 μM Rabin8. The decrease in mant fluorescence was used as a measure of mantGDP release.",
    "ncbi_link": "Rab8A: 4218"
  },
  {
    "caption": "Rab8A Ser111 phosphorylation impairs Rabin8 interaction in cells. Rab8A KO HeLa cells were transfected with wild‐type (WT), S111E or S111A HA‐Rab8A. Whole‐cell lysates (1 mg) were immunoprecipitated with anti‐HA agarose and immunoblotted with Rabin8 or anti‐HA antibody. Lysates were immunoblotted with Rabin8 or anti‐HA antibody to confirm equivalent expression of Rabin8 and WT and mutant HA‐Rab8A in extracts.",
    "ncbi_link": "Rab8A: 4218"
  },
  {
    "caption": "Agar plugs containing actively growing cultures of wild type S. sclerotiorum (strain 1980) and the OA deficient A2 mutant were inoculated onto Col-0 and ced-9 expressing Arabidopsis leaves. (A) Wild type inoculations onto Col-0 plants resulted in typical lesions for this pathogen including a rapid, spreading cell death; however, infection was completely suppressed in ced-9 expressing plants. The expression of this gene had no effect on the A2 phenotype.",
    "ncbi_link": "Col-0: 
OA: 
ced-9: 3565776"
  },
  {
    "caption": "Transmission Electron Microscopy (TEM) fungal inoculated tomato leaves.Representative TEM images from four independent experiments. (A, G); Healthy non-inoculated leaf tissue. (B-F) Tomato leaves inoculated with the OA deficient A2 strain. (H,I) Tomato leaves inoculated with wild type S. sclerotiorum. Arrows, autolysosomal/autophagosomal-like structures; C, chloroplast; V, vacuole; N, nucleus; Circle, active dismantlement of chloroplast; Rectangle, chromatin condensation within the nucleus. Black scale bars = 2 µm, white scale bars = 1 µm. Sections were examined with a Phillips Morgagni 268 transmission electron microscope at an accelerating voltage of 80 kV. Digital images were recorded with a MegaViewIII digital camera operated with iTEM software.",
    "ncbi_link": "OA: "
  },
  {
    "caption": "(A,B) Agar plugs containing actively growing cultures of the OA deficient A2 mutant were inoculated onto leaves of Arabidopsis Col-0 and select Arabidopsis autophagy mutant plants. These mutants showed enhanced susceptibility to the normally non-pathogenic A2 strain. Lesion diameter was monitored over time and all images were recorded 48 hours post inoculation.",
    "ncbi_link": "Col-0: 
OA: "
  },
  {
    "caption": "(A) NBT treated Arabidopsis (Col-0 and two independent atg8a mutant lines) following agar plug inoculation with the A2 mutant. Images were collected 48 hours post inoculation. Dotted lines represent the edge of the observable legion.",
    "ncbi_link": "Col-0: 
atg8a: 828287"
  },
  {
    "caption": "(B) RT-PCR was used to evaluate the transcript levels of three catalases (CAT1, 2, and 3) and three superoxide dismutases in Col-0 plants following inoculation with wild type S. sclerotiorum (black bars) and the A2 mutant strain (grey bars). *>2 fold change, **>5 fold change.",
    "ncbi_link": "Col-0: 
CAT1: 838652"
  },
  {
    "caption": "(I) mRNA levels for classical EMT markers in cells treated as in (F) were measured by qRT-PCRs relative to Ctcf and fold change as compare to untreated and plotted on the y-axis. Mean and SEM is plotted from three independent biological replicates.",
    "ncbi_link": "Ctcf: "
  },
  {
    "caption": "Depletion of Prkrir, Pcbp4 and Tsc22d1 rescues TGF-β-induced reduction in the rate of cell division. (A) Lineage trees tracked by live imaging under control, Non treated control (NTC) and siRNA-mediated depletion of factors (X= cell death/cells could not be tracked till the end).",
    "ncbi_link": "Pcbp4: 59092
Prkrir: 72981
Tsc22d1: 21807"
  },
  {
    "caption": "PRKRIR, PCBP4 and TSC22D1 are crucial for maintenance of the mesenchymal fate. (A) Scratch assay in MDA-MB-231 cells treated for four days with DMSO or JNKi. Scale bar, 200 μm; 20 X magnification. Mean and SEM is plotted from three independent biological replicates.",
    "ncbi_link": "PCBP4: 57060
PRKRIR: 5612
TSC22D1: 8848"
  },
  {
    "caption": "(B) mRNA levels for key EMT marker genes in MDA-MB-231 treated with DMSO or JNKi for 4 days were measured by qRT-PCR relative to Ctcf and plotted on the y-axis. Mean and SEM is plotted from three independent biological replicates",
    "ncbi_link": "Ctcf: "
  },
  {
    "caption": "(C) mRNA levels for transcription factors in isogenic epithelial (MDA-MB-361) and mesenchymal (MDA-MB-231) breast cancer cells were measured by qRT-PCR relative to Ctcf and plotted on the y-axis. Mean and SEM is plotted from three independent biological replicates.",
    "ncbi_link": "Ctcf: "
  },
  {
    "caption": "(D) Scratch assay in MDA-MB-231 cells transfected with NTC or siRNA against PRKRIR, NFIL3, PCBP4 and TSC22D1 for 4 days as in A. Mean and SEM is plotted from three independent biological replicates as bar plot on right .",
    "ncbi_link": "NFIL3: 4783
PCBP4: 57060
PRKRIR: 5612
TSC22D1: 8848"
  },
  {
    "caption": "(F) mRNA levels of key EMT marker genes in MDA-MB-231 and MDA-MB-231 transfected with either empty vector or vector overexpressing PCBP4 or TSC22D1 for 48 hours and then treated with the JNK inhibitor (SP600125) for 24 hours were measured by qRT-PCRs relative to Ctcf and plotted on the y-axis. Mean and SEM is plotted from three independent biological replicates. Plotted Mean ± SEM of three biological replicates. * p<0.05, ** p<0.01, *** p< 0.001, Student's t-test.",
    "ncbi_link": "Ctcf: 
PCBP4: 57060
TSC22D1: 8848"
  },
  {
    "caption": "(C) mRNA levels for representative genes highlighted in (A) for cells treated like in (Fig 5D) were measured by qRT-PCR relative to Ctcf and plotted on the y-axis. Mean and SEM is plotted from three independent biological replicates.",
    "ncbi_link": "Ctcf: "
  },
  {
    "caption": "(G) ChIP assay using anti-Flag antibody following expression of Flag-HA tagged TSC22D1 in MDA-MB-231 cells. Quantitative PCRs were performed for indicated gene promoters and enrichments are plotted on the y-axis as ratio of precipitated DNA (bound) to total input DNA and then further divided by the same obtained in the empty vector transfected cells. SEM is derived from independent biological replicates.",
    "ncbi_link": "TSC22D1: 8848"
  },
  {
    "caption": "(H) mRNA levels for PRKRIR, PCBP4, TSC22D1 in non-invasive (DCIS) (n=20) and invasive tumor (n=20) samples were measured by qRT PCRs relative to TBP and plotted on the y-axis. ZEB1 was used as an established positive control for invasive tumors. Plotted Mean ± SEM of three biological replicates. * p<0.05, ** p<0.01, *** p< 0.001, Student's t-test.",
    "ncbi_link": "TBP: 
PCBP4: 57060
PRKRIR: 5612
TSC22D1: 8848
ZEB1: 6935"
  },
  {
    "caption": "Newly identified transcription factors are similarly upregulated during neurogenesis and function in neuronalmigration. (A) RT-qPCR analysis for key EMT markers in embryonic stem cells (ES), neuronal progenitors (NP) and terminally differentiated neurons (TN). mRNA levels were measured by RT-qPCR relative to Ctcf and plotted on the y-axis. Error bars represent SEM from independent biological replicates.",
    "ncbi_link": "Ctcf: "
  },
  {
    "caption": "(C) RNA levels of Pcbp4, Prkrir and Tsc22d1 during neuronal differentiation as shown in A, measured by RT-qPCR relative to Ctcf and plotted on the y-axis. Error bars represent SEM from independent biological replicates.",
    "ncbi_link": "Ctcf: 
Pcbp4: 59092
Prkrir: 72981
Tsc22d1: 21807"
  },
  {
    "caption": "(D) RNA levels of Pcbp4, Prkrir, Tsc22d1, represented by average counts derived from previously published microarray data of independent biological replicates from neurons treated with DMSO or JNK inhibitor SP600125 (JNKi) for 6 hours.",
    "ncbi_link": "Pcbp4: 59092
Prkrir: 72981
Tsc22d1: 21807"
  },
  {
    "caption": "(E) RNA levels of Tsc22d1 and three Tsc22d1 target genes during various stages of neuronal differentiation shown in (A), measured by RT-qPCR relative to Ctcf and plotted on the y-axis. Error bars represent SEM from independent biological replicates.",
    "ncbi_link": "Ctcf: 
Tsc22d1: 21807"
  },
  {
    "caption": "(F) RNA levels of Tsc22d1 and the same three target genes is shown as average normalized tag counts derived from RNA-seq data from Ventricular Zone (VZ), Sub-Ventricular Zone (SVZ) and Cortical plate (CP) of E14.5 mouse Cortex.",
    "ncbi_link": "Tsc22d1: 21807"
  },
  {
    "caption": "(I) A representative image from immunofluorescence analysis performed with anti-GFP and anti-Tbr1 antibody that shows retention of GFP positive cells below the Tbr1 layer in Tsc22d1 knockdown brain as compared to the control brain. The bar plot on the right side shows quantification of migrated GFP positive cells in control and Tsc22d1 depleted mouse brain with respect to the Tbr1 staining. y axis represent percentage of cells above or below the Tbr1 stain region. Error bars represent SEM from 3 independent biological replicates. * p<0.05, ** p<0.01, *** p< 0.001, Student's t-test.",
    "ncbi_link": "Tsc22d1: 21807"
  },
  {
    "caption": "(A-V) Age-dependent muscle protein levels of ALT2 (A), GOT2 (C), OGDH (E), GOT1 (G), ALT1 (I), AGC1 (K), SUCLA2 (M), BCAT2 (O), BCKDH (Q), PCCA (S), and MUT (U), estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blots of muscle lysates from 170-200 days old mice separated by denaturing SDS-PAGE and probed for ALT2 (B), GOT2 (D), OGDH (F), GOT1 (H), ALT1 (J), AGC1 (L), SUCLA2 (N), BCAT2 (P), BCKDHB (R), PCCA (T), and MUT (V) and GAPDH (B, D, F, H, J, L, N, P, R, T, V). : In panels data are presented as Mean ± SD. COX10 KO (n=4), CTL (n=4). Statistically significant differences between the two groups were estimated by unpaired two-tailed Student's test. *, p<0.05 **, p<0.005 COX10 KO vs CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(X) Muscle fractional incorporation of M+6 of glutamate, M+5 of αKG, M+4 of fumarate, M+4 of malate, M+3 of alanine and M+3 of lactate, in 200 days COX10 KO and CTL mice IP injected with [13C5, 15N]-glutamate. In panels X data are presented as Mean ± SEM. In panel X, COX10 KO (n=4), CTL (n=4). Statistically significant differences between the two groups were estimated by unpaired two-tailed Student's test. *, p<0.05 **, p<0.005 COX10 KO vs CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(Z) Muscle fractional incorporation of M+6 of valine, M+5 of α-KIV, M+4 of β-ΗΙΒ, M+3 of propionyl carnitine, in 200 days COX10 KO and CTL mice IP injected with [13C5, 15N]-valine. In panels Z, data are presented as Mean ± SEM. In panel Z, COX10 KO (n=3), CTL (n=3). Statistically significant differences between the two groups were estimated by unpaired two-tailed Student's test. *, p<0.05 **, p<0.005 COX10 KO vs CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(B) Age-dependent Ph-4EBP1/4E-BP1 ratio in COX10 KO expressed relative to same age CTL set at 1. (C) Representative western blot of muscle lysates from 200 days old mice separated by denaturing SDS-PAGE and probed for Ph-4E-BP1 and for 4E-BP1. In panels data are presented as Mean ± SD. COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. same age CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(D) Age-dependent protein levels of Ph-4E-BP1 in COX10 KO muscle estimated by band densitometry normalized by GAPDH expressed relative to 50 days COX10 KO set at 1. (E) Western blots of muscle lysates from 50, 100, and 200 days old COX10 KO mice, separated by denaturing SDS-PAGE and probed for Ph-4E-BP1 and GAPDH. In panel D, data are presented as Mean ± SD. #, p<0.05 COX10 KO vs. COX10 KO at different ages. 50d (n=3), 100d (n=3), 200d (n=3).",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent protein levels of SESTRIN 2 (F), REDD1 (H), LC3II (J) estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blot of muscle lysates from 100 and 170-200 days old mice separated by denaturing SDS-PAGE and probed for SESTRIN 2 (G), REDD1 (I), LC3II (K) In panels data are presented as Mean ± SD. COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. same age CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent protein levels of MURF1 (L), and ATROGIN1 (N) estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blot of muscle lysates from 100 and 170-200 days old mice separated by denaturing SDS-PAGE and probed for (M), ATROGIN1 (O), and GAPDH In panels data are presented as Mean ± SD. COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. same age CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent levels of ATF4 (B), MTHFD2 (D) estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blot of muscle lysates from 200 days old mice separated by denaturing SDS-PAGE and probed for ATF4 (C), MTHFD2 (E) and GAPDH In panels data are presented as Mean ± SD. *, p<0.05 COX10 KO vs. same age CTL. For each age, COX10 KO (n=4), CTL (n-4).",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent levels of ASNS (F), and HSP60 (H), estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blot of muscle lysates from 200 days old mice separated by denaturing SDS-PAGE and probed for ASNS (G), and HSP60 (I) and GAPDH In panels data are presented as Mean ± SD. *, p<0.05 COX10 KO vs. same age CTL. For each age, COX10 KO (n=4), CTL (n-4).",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(D-I) Age-dependent levels of HADH (D), ACOT2 (F), and ACOT9 (H), estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Representative western blot of muscle lysates from 200 days old mice separated by denaturing SDS-PAGE and probed for HADH (E), ACOT2 (G), ACOT9 (I), and GAPDH (E, G, I). In panels , data are presented as Mean ± SD. COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. same age CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(K, L) Levels of acylcarnitine, 3-OH acylcarnitine, fatty acid and 3-OH fatty acid in MERRF muscle (K) and plasma (L) by LC-MS analysis, expressed relative to CTL. In panels data by LC-MS analysis are presented as Mean ± SEM. In panels A and C, 50, 100, 200d: COX10 KO (n=6), CTL (n=6). *, p<0.05 COX10 KO vs. same age CTL. In panels K and L, muscle: MERRF (n=10), CTL (n=15); plasma: MERRF (n=9), CTL (n=25). *, p<0.05 MERRF vs. CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent muscle protein levels of P5CS (B), PYCR1 (D) estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Data are presented as Mean ± SD. *, p<0.05 COX10 KO vs. same age CTL. Representative western blots of muscle lysates from 170 days old mice separated by denaturing SDS-PAGE and probed for P5CS (C), PYCR1 (E) GAPDH In panels data are normalized to same age CTL set to 1. Data are presented as Mean ± SD. 50, 100, 200d: COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "Age-dependent muscle protein levels of PYCR2 (F) OAT (H), estimated by band densitometry normalized by GAPDH, in COX10 KO expressed relative to same age CTL set at 1. Data are presented as Mean ± SD. *, p<0.05 COX10 KO vs. same age CTL. Representative western blots of muscle lysates from 170 days old mice separated by denaturing SDS-PAGE and probed for , PYCR2 (G), OAT (I), and GAPDH : In panels data are normalized to same age CTL set to 1. Data are presented as Mean ± SD. 50, 100, 200d: COX10 KO (n=4), CTL (n=4). *, p<0.05 COX10 KO vs. CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(A-C) Plasma levels of Leptin (A), soluble Leptin Receptor (LepR), (B) and Free Leptin Index (C) by ELISA, in 200 days old CTL and COX10 KO mice. In panels A-C, data are presented as Mean ± SD. COX10 KO (n=5), CTL (n=5). *, p<0.05 COX10 KO vs. CTL.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(N) Age-dependent grip strength of COX10 KO mice treated with RU-486 and vehicle. The black arrow indicates the beginning of the treatment at 43 days. In panel data are presented as Mean ± SEM. Panel N: KO+RU486 (n=6), KO (n=4).",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "(P) Visceral fat deposits of COX10 KO mice treated with RU-486 and vehicle at 100 days of age. In panel P, data are presented as Mean ± SD. KO+RU486 (n=6), KO (n=6). *, p<0.05 KO+RU486 vs. KO. Statistically significant differences between the two groups for all panels were estimated by unpaired two-tailed Student's test.",
    "ncbi_link": "COX10: 70383"
  },
  {
    "caption": "C Growth phenotype of H subunit mutants. Deletion of V-ATPase subunits from yeast results in a conditional lethal phenotype (Vma-) characterized by an inability to grow at pH 7.5 in the presence of 60 mM CaCl2 (upper panel), but growth is observed at pH 5 (lower panel). Subunit H mutations were introduced on a plasmid into a yeast strain deleted for the H subunit and their phenotypes assessed. Both humanH subunit isoforms (HsH1, HsH2), a chimeric H subunit (HChim) containing ScHNT and HsHCT, mutations in yeast intended to mimic the length of the human H loop sequence and accessibility (Hloop), and a point mutation of the conserved aspartic acid residue in the loop sequence (HD410A) are shown compared to the H subunit deletion (ΔH) and wild type H on a plasmid (H WTpl). All grow on pH 5 medium, but the human isoforms failed to complement the deletion phenotype.",
    "ncbi_link": "H subunit: 51606
Subunit H: 856148"
  },
  {
    "caption": "D ATPase activity of H subunit mutants. The ScV1 sectors were purified from each strain that complemented the phenotype as well as from ScV1ΔH, for comparison of MgATPase activity. Average specific activities are shown plotted +/- s.e.m from two independent purifications. The ScV1 sector containing chromosomally encoded H subunit shows no detectable MgATPase activity (Parra et al, 2000; Zhang et al, 2003), whereas ScV1containing plasmid-borne wild type H (H WTpl) exhibits low levels of activity likely due to reduced expression from the low copy plasmid. The HChim and HLoop mutants lead to a loss of activity silencing, displaying nearly the same activity as ScV1ΔH.",
    "ncbi_link": "H subunit: 51606
H subunit: 856148"
  },
  {
    "caption": "E SDS-PAGE and Western Blot analysis of ScV1 preparations. Left panel, 15% SDS PAGE of ScV1 purified from the subunit H mutant and WT strains. Note that H WTch is purified from a yeast strain deleted for the C subunit (used for crystallization). The remaining strains contain subunit C, which is co-purified with ScV1 in varying levels. Note that while H WTch ScV1, which is expressed from a strain deleted for subunit C, displays no detectable MgATPase activity, the H subunit mutants co-purified with the most C subunit display the least activity, suggesting that absence or presence of subunit C has no effect on MgATPase activity. Right panel, immunoblot probed with an antibody directed against the N-terminal Myc tagged mutant H subunits expressed from a plasmid. Note that the levels of mutant H expression does not appear to vary from strain to strain.",
    "ncbi_link": "H subunits: 51606
subunit H: 856148"
  },
  {
    "caption": "(D) Pulldown assay with in vitro-translated Mam187-191 (wild-type and alanine mutants) and Hrr251-394 K38R. Mam1 mutations also disrupt Hrr25 binding when the two are co-expressed in E. coli (Figure EV6B). Bottom: Sporeviability of MAM1 mutant strains (see Table EV2 for strains; strains tested are KC549, KC560, KC566, KC552, KC554, KC556, and KC558; 46-48 tetrads were dissected for each strain). \"--\" indicates that this mutation was not tested for sporeviability.",
    "ncbi_link": "MAM1: 856843"
  },
  {
    "caption": "(A) ADP-Glo ATPase assay showing stimulation of S. cerevisiae Hrr251-394 (blue circles), Hrr251-394 K38R (red diamonds), Hrr25 full-length:Mam187-191 (black triangles), Hrr251-394:Mam187-191 (orange squares), and Hrr251-394:Mam187-191 R131A (green triangles) by bovine casein. See Figure EV6A for SDS-PAGE analysis of purified proteins.",
    "ncbi_link": "Hrr25: 855897
Mam1: 856843"
  },
  {
    "caption": "(B) Stimulation of Hrr251-394, Hrr251-394:Mam187-191, and Hrr251-394:Mam187-191 R131A by ATP, measured using an enzyme-coupled ATPase assay.",
    "ncbi_link": "Mam1: 856843"
  },
  {
    "caption": "(C) ADP-Glo assay showing the effect of added CK1-7 on Hrr251-394, Hrr251-394:Mam187-191, and Hrr251-394:Mam187-191 R131A.",
    "ncbi_link": "Mam1: 856843"
  },
  {
    "caption": "(A) Phos-tag gels showing phosphorylation of purified S. cerevisiae Mtw1 complex by Hrr251-394 and Hrr251-394:Mam187-191. Asterisks denote N-terminal proteolytic cleavage products of Dsn1, with the red asterisk denoting a previously-characterized product lacking the first 171 residues (Hornung et al, 2011).",
    "ncbi_link": "Hrr25: 855897"
  },
  {
    "caption": "B A549 cells were transfected with a plasmid encoding Flag-tagged PB1-F2 derived from the PR8 or 1918 strain and treated with the proteasome inhibitor MG132 (25 μM) or vehicle for 6 h before harvesting. PB1-F2 transcripts were analyzed by semi-quantitative RT-PCR (top panel), and The PB1-F2 protein was analyzed by Western blotting with monoclonal anti-Flag antibody.",
    "ncbi_link": "Flag: 
PB1-F2: 3802042"
  },
  {
    "caption": "C Representative immunofluorescence images showing expression of PB1-F2 (red). A549 cells were transfected with plasmids encoding indicated PB1-F2. At 18 h after transfection, cells were treated with MG132 for 6 h and subjected to immunofluorescence analysis. Magnification, ×100; scale bar, 100 μm.",
    "ncbi_link": "PB1-F2: 3802042"
  },
  {
    "caption": "D Each HA-tagged PB1-F2 was transfected into 293T cells with or without Flag-ubiquitin. At 18 h after transfection, cells were treated with MG132 for 6 h. The lysates were immunoprecipitated with anti-HA antibody and analyzed by Western blotting with anti-Flag antibody. PR8, A/Puerto Rico/8/34 (H1N1); 1918, A/Brevig Mission/1/1918 (H1N1).",
    "ncbi_link": "HA: 
PB1-F2: 3802042"
  },
  {
    "caption": "B-D A549 cells were transfected with the indicated plasmids encoding Flag-tagged PB1-F2 derived from the PR8 or 1918 strain and chimeric PB1-F2 mutants. At 18 h after transfection, cells were treated with or without MG132 for 6 h. The expression of PB1-F2 and control genes was detected by semi-quantitative RT-PCR (upper panel) or Western blotting (lower panel). Results shown are representative of three independent experiments.",
    "ncbi_link": "Flag: 
PB1-F2: 3802042"
  },
  {
    "caption": "E Representative immunofluorescence images of PB1-F2 expression in A549 cells. Cells transfected with the Flag-tagged PB1-F2 plasmid were stained with anti-Flag (red) antibody and analyzed by immunofluorescence assay. Magnification, ×400; scale bar, 50 μm.",
    "ncbi_link": "Flag: 
PB1-F2: 3802042"
  },
  {
    "caption": "A Relative activity of NF-kB luciferase reporter was measured in A549 cells transfected with plasmids encoding PB1-F2. The mRNA levels of pro-inflammatory cytokines were determined by semi-quantitative RT-PCR. All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "luciferase: 
PB1-F2: 3802042"
  },
  {
    "caption": "Cells were transfected with PB1-F2-expressing plasmids. Relative IFNβ mRNA levels were determined by semi-quantitative RT-PCR (top) and qPCR (bottom). All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "IFNβ: 3456
PB1-F2: 3802042"
  },
  {
    "caption": "C U937 cells were co-transfected with the IFNβ luciferase reporter plasmid and the PB1-F2 or NS1 expressing plasmid and treated with polyI:C for 12 h before harvesting. IFNβ promoter activity was determined by luciferase reporter assay. All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "luciferase: 
IFNβ: 3456
NS1: 956533
PB1-F2: 3802042"
  },
  {
    "caption": "Cells were infected for 24 h with each virus at 1 MOI. The mRNA level of IFNβ was determined by semi-quantitative RT-PCR, and PB1-F2 protein expression was assessed by Western blotting. All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "IFNβ: 3456"
  },
  {
    "caption": "E Cells were transfected with each plasmid encoding PB1-F2. 18 h after transfection, cells were treated with MG132 for 6 h and the level of IFNβ mRNA was determined by semi-quantitative RT-PCR (left) and qPCR (right). PB1-F2 protein expression was assessed by Western blotting. All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "IFNβ: 3456
PB1-F2: 3802042"
  },
  {
    "caption": "F A549 cells were transfected with PB1-F2 clones mutated at positions 68 and 69; 24 h after transfection, the IFNβ mRNA level and PB1-F2 protein expression were determined by semi-quantitative RT-PCR and Western blotting, respectively (left). The relative expression level of IFNβ mRNA was also analyzed by qPCR (right). All data are shown as mean (±SEM) from at least three independent experiments (*p < 0.05, **p <0.01, ***p <0.001).",
    "ncbi_link": "IFNβ: 3456
PB1-F2: 3802042"
  },
  {
    "caption": "C Mice (n = 5 or 6 per group) were infected with viruses (1000 pfu) carrying PR8 PB1-F2 with the I68T, L69P, or I68T+L69P mutation. Body weight changes and survival rate were monitored daily. Detailed analyses on the virulence necessitated the monitoring of body weight below the standard level (80%) of mortality.",
    "ncbi_link": "PB1-F2: 3802042"
  },
  {
    "caption": "F Mice (5-9 per group) were infected with 500 pfu of each virus. At 2 days post-infection, IFNβ mRNA levels were determined by qPCR.",
    "ncbi_link": "IFNβ: 15977"
  },
  {
    "caption": "E Analysis of interaction between DDX3 and 1918 PB1-F2. Cells were transfected with indicated plasmids; 18 h later, cells were treated with MG132 for 6 h. Cell lysates were immunoprecipitated with anti-HA antibody. Proteins were detected by immunoblotting with the indicated antibodies (left panel). IAV-infected cell lysates were immunoprecipitated with anti-PB1-F2 antibody and immunoblotted with the indicated antibodies (middle panel). Purified recombinant 1918 PB1-F2 protein was incubated with recombinant LysRS or LysRS-DDX3, and the interaction was analyzed by immunoblotting (right panel). Results were confirmed in three independent experiments, and representative data are shown.",
    "ncbi_link": "LysRS: 3735"
  },
  {
    "caption": "F Analysis of interaction between DDX3 and PB1-F2 mutants. A549 cells were transfected with the indicated clones; 18 h after transfection, cells were treated with MG132 for 6 h and analyzed by immunoprecipitation. Results were confirmed in three independent experiments, and representative data are shown.",
    "ncbi_link": "PB1-F2: 3802042"
  },
  {
    "caption": "H Representative fluorescence images showing expression level of GFP-DDX3 (green). A549 cells were co-transfected with plasmids encoding the GEP-DDX3 and Flag-tagged PR8 or 1918 PB1-F2. At 18 h after transfection, cells were treated with MG132 for 6 h and subjected to fluorescence analysis. Results were confirmed in three independent experiments, and representative data are shown.",
    "ncbi_link": "Flag: 
GEP: 
DDX3: 1654
PB1-F2: 3802042"
  },
  {
    "caption": "K A549 cells were transfected with the indicated plasmids, and IFNβ mRNA levels were determined by semi-quantitative RT-PCR (top) and qPCR (middle). IFNβ promoter activity was determined by luciferase reporter assay (bottom). Results were confirmed in three independent experiments, and representative data are shown.",
    "ncbi_link": "IFNβ: 3456"
  },
  {
    "caption": "Groups of five mice were intranasally infected with IAV (1918), and recombinant DDX3 protein was administered intranasally. Two days post-infection, the expression level of IFNβ in the lungs was analyzed by semi-quantitative RT-PCR (left panel) and qPCR (right panel). A p value of <0.05 was considered significant (** p < 0.01).",
    "ncbi_link": "IFNβ: 15977"
  },
  {
    "caption": "E Strand-specific RT-qPCR asDOG1 expression analysis of 3-day Col-0 (WT) drought-treated vs. control plants.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "F The asDOG1 expression level (black line) is reduced while DOG1 sense expression (grey line) is increased after application of ABA. Leaves of mature Col-0 (WT) 40-day-old plants were sprayed with ABA and collected 0, 6 and 10 h later for RNA extraction and RT-qPCR. Signals were normalized against the level of the UBC transcript. The data points are the averages for at least three biological replicates and are normalized against the mock-treated value. Error bars represent standard deviation.* and *** represent t-test P-values of < 0.05 and < 0.001, respectively.",
    "ncbi_link": "DOG1: 834623
UBC: 832645"
  },
  {
    "caption": "A Col-0 (WT) and dog1-3 mutant plants were either watered normally or subjected to water withdrawal for 5 days and then watered again and allowed to recover for 2 days. A picture of a representative experiment is shown. Scale bar, 2 cm.",
    "ncbi_link": "dog1: 834623"
  },
  {
    "caption": "B Quantification of recovered and dead Col-0 (WT), null-3 and dog1-4 plants; plants were scored as dead when unable to grow and produced offspring after an extended recovery period.",
    "ncbi_link": "dog1: 834623"
  },
  {
    "caption": "C Analysis of DOG1 sense expression in drought-treated vs. control Col-0 (WT) and dog1-3 mutant plants.",
    "ncbi_link": "dog1: 834623
DOG1: 834623"
  },
  {
    "caption": "D dog1-3 mutant plants are defective in the regulation of the majority of the tested drought marker genes. Col-0 (WT) and dog1-3 mutant plants were subjected to drought for 3 days and the expression of five marker genes was determined using RT-qPCR. Error bars represent standard deviation, and *, ** and *** represent t-test P-values of < 0.05, < 0.01 and < 0.001, respectively.",
    "ncbi_link": "dog1: 834623"
  },
  {
    "caption": "C A truncated construct that lacks the DOG1 antisense promoter region (pDOG1shDOG1::LUC) is not induced by ABA and is highly expressed throughout development. The graphs show mean emitted light intensity per plant.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "D Representative picture of mock- and ABA-treated pDOG1shDOG1::LUC plants. Scale bar: 1cm.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "E RT-qPCR analysis of DOG1 sense mRNA level.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "G The pASDOG1::LUC reporter is silenced by the application of ABA, while mutation of TATA elements in the asDOG1 promoter (pASDOG1∆TATA::LUC) leads to attenuation of expression in the presence and absence of ABA.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "H Mutation of TATA elements in the asDOG1 promoter leads to high-level DOG1 sense expression and non-responsiveness to ABA. Error bars represent standard deviation and *, ** and *** represent t-test P-values of < 0.05, < 0.01 and < 0.001, respectively.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "A Plants expressing the truncated asDOG1 promoter-deficient version pDOG1shDOG1::LUC are more resistant to drought than plants expressing the full-length genomic version pDOG1::LUC-DOG1. Three independent lines are shown for each construct, following 10 days of water deprivation. Scale bar, 2 cm.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "B RT-qPCR quantification of selected drought marker genes in mock- and ABA-treated Col-0 (WT) and two independent pDOG1shDOG1::LUC transgenic lines. Error bars represent standard deviation and *, ** and *** represent t-test P-values of < 0.05, < 0.01 and < 0.001, respectively.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "(g) RKO cells expressing inducible HA-ATG4B-C74A were treated with doxycycline (DOX induction) for five days and then incubated in DOX-free medium for 24 h (DOX washout). Bafilomycin A1 was added with or without PIK-III at the beginning of the washout period (lanes 5 and 6). Steady-state levels of ATG4B, LC3 and GAPDH were visualized by western blotting. Uncropped images of blots are shown in Supplementary Fig. 7.",
    "ncbi_link": "ATG4B: 23192"
  },
  {
    "caption": "(d) The levels of NCOA4 and p62 in ATG7 wild-type (+/+), heterozygous (+/−) or homozygous knockout (−/−) DLD1 clones 1 and 2 were determined",
    "ncbi_link": "ATG7: 10533"
  },
  {
    "caption": "(d) DLD1 parental or NCOA4−/− cells (clones 1 and 2; KO-1, KO-2) were starved for 6 h and the levels of NCOA4, FTH1, FTL and GAPDH determined.",
    "ncbi_link": "NCOA4: 8031"
  },
  {
    "caption": "(e) DLD1 parental or NCOA4−/− cells were cultured in the presence or absence of bafilomycin A1overnight, fixed and processed for confocal immunofluorescence microscopy to determine the cellular distribution of endogenous ferritin (FTH1-FTL) and LAMP2. Regions outlined with white dashed lines are magnified to the right of each panel. Scale bars of full and zoomed panels correspond to 10 and 2 μm respectively. Uncropped images of blots are shown in Supplementary Fig. 7.",
    "ncbi_link": "NCOA4: 8031"
  },
  {
    "caption": "(b) DLD1 parental or NCOA4−/− cell extracts were resolved using SEC and each fraction was analysed for the presence of NCOA4, FTH1 and FTL by western blot.",
    "ncbi_link": "NCOA4: 8031"
  },
  {
    "caption": "(c) NCOA4−/− cells were transfected with control or SBP-NCOA4 cDNA for 36 h and incubated overnight in the presence or absence of the indicated inhibitors, lysed and the occurrence of the faster-migrating FTH1 band was determined.",
    "ncbi_link": "NCOA4: 8031"
  },
  {
    "caption": "(d) Endogenous NCOA4 immunoprecipitations from DLD1 parental, FTH1−/− or FTL−/− (clones 1 and 2 for each genotype) protein extracts. The presence of FTH1 and FTL was detected by western blot. Uncropped images of blots are shown in Supplementary Fig. 7.",
    "ncbi_link": "FTH1: 2495
FTL: 2512"
  },
  {
    "caption": ". (b) DLD parental or NCOA4−/− cells were incubated in the presence or absence of DFX and the levels of FTH and FTL were determined.",
    "ncbi_link": "NCOA4: 8031"
  },
  {
    "caption": "(c) Ncoa4−/− mouse embryonic stem cells were analysed for Ncoa4 and Fth1 by western blotting. Note the complete absence of the lower Fth1 band consistent with earlier findings.",
    "ncbi_link": "Ncoa4: 27057"
  },
  {
    "caption": "(d) Representative haemotoxylin and eosin staining of spleens from control or Ncoa4−/− mice is shown and brown pigmented regions apparent in Ncoa4−/− sections are indicated (white arrows).",
    "ncbi_link": "Ncoa4: 27057"
  },
  {
    "caption": "(e) The presence of iron in spleens from control or Ncoa4−/− mice was determined using Perls' Prussian blue staining. Representative micrographs (left panels) or magnifications (right panels) are shown. Scale bars correspond to 100 μm and 20 μm in full and magnified panels respectively. (f) Quantitative image analysis of the data shown in e was performed as described in the Methods. Each data point represents relative iron levels in a single mouse spleen section and horizontal lines are means of each group (n = 6 mice per group; ∗P 0.0006 for unpaired t-test). Uncropped images of blots are shown in Supplementary Fig. 7.",
    "ncbi_link": "Ncoa4: 27057"
  },
  {
    "caption": "(F-I) Representative immunofluorescence images of HeLa cells stably expressing GFP-Cyclin B2 (F) or GFP-Cyclin B1 (H). The cells were transfected with siControl or siMad2 for 36 h followed by treatment with nocodazole plus MG132 for 2 h. Then cells were fixed and co-stained for Mad2 (red) and DNA (blue). Scale bar, 10 µm. Scatter graphs illustrating kinetochore intensity of GFP-Cyclin B2 (G) or GFP-Cyclin B1 (I) in cells treated as in F and H, respectively. Bars represent the mean kinetochore intensity (±SD) normalized to values of the siControl group. Each dot represents one cell (≥30 cells from three independent experiments)",
    "ncbi_link": "Mad2: 4085"
  },
  {
    "caption": "(B) Flag immunoprecipitation assay. Flag-tagged Cyclin B2-WT, Cyclin B2-4A, or Cyclin B1 were expressed in 293T cells and purified with anti-Flag M2 beads. Subsequently, the beads were incubated with mitotic HeLa lysates for 2 h, and, following extensive washes, immunoprecipitatates were resolved by SDS-PAGE and analyzed by Western blotting using anti-Flag antibody and anti-Mad2 antibody.",
    "ncbi_link": "Flag: 
Cyclin B2: 9133"
  },
  {
    "caption": "(C) Flag immunoprecipitation assay. 293T cells were co-transfected with Flag-Cyclin B2-WT or Flag-Cyclin B2-4A together with GFP (negative control) and GFP-CDK1. After 36 h, the cells were collected and lysed, and immunoprecipitation was accomplished with anti-Flag M2 beads. Immunoprecipitation samples were resolved by SDS-PAGE and analyzed by Western blotting using anti-GFP antibody and anti-Flag antibody.",
    "ncbi_link": "Flag: 
GFP: 
Cyclin B2: 9133
CDK1: 983"
  },
  {
    "caption": "(D) Representative immunofluorescence images of HeLa cells transfected with GFP-Cyclin B2-WT or GFP-Cyclin B2-4A. After 36 h of transfection, cells were treated with nocodazole for 2 h. Then cells were fixed and co-stained for ACA (red) and DNA (blue). (E) Scatter graphs illustrating kinetochore intensity of GFP-Cyclin B2-WT/4A treated as in D. Bars represent the mean kinetochore intensity (±SD) normalized to the values of GFP-Cyclin B2-WT. Each dot represents one cell (≥30 cells from three independent experiments).",
    "ncbi_link": "GFP: 
Cyclin B2: 9133"
  },
  {
    "caption": "(A) HeLa cells were transfected with siControl or siCyclin B2. At 36 h after transfection, cells were collected and lysed. The samples were resolved by SDS-PAGE and analyzed by Western blotting using anti-Cyclin B2 antibody, anti-Cyclin B1 antibody, and anti-tubulin antibody",
    "ncbi_link": "Cyclin B2: 9133"
  },
  {
    "caption": "(B) Representative stills illustrating mitotic progression in mCherry-H2B expressed cells treated with Control siRNA or Cyclin B2 siRNA. Images were acquired at the indicated time points after the start of NEBD. The arrow indicates lagging chromosomes",
    "ncbi_link": "Cyclin B2: 9133"
  },
  {
    "caption": "(E) Representative stills illustrating mitotic progression in mCherry-H2B expressed cells depleted of endogenous Cyclin B2 and rescued with GFP-Cyclin B2-WT or GFP-Cyclin B2-4A. Images were acquired at the indicated time points after the start of NEBD",
    "ncbi_link": "GFP: 
Cyclin B2: 9133"
  },
  {
    "caption": "Representative immunofluorescence images of HeLa cells transfected with siControl or siCyclin B2. After 36 h of transfection, cells were treated with nocodazole for 2 h. Then cells were fixed and co-stained for Mad2 (green) in D, ACA (red), and DNA (blue) Representative immunofluorescence images of HeLa cells co-transfected with siCyclin B2 plus GFP-tagged Cyclin B2-WT or Cyclin B2-4A. At 36 h post-transfection, cells were treated with nocodazole for 2 h. Then cells were fixed and co-stained for Mad2 (red) in DNA (blue)",
    "ncbi_link": "GFP: 
Cyclin B2: 9133"
  },
  {
    "caption": "Representative immunofluorescence images of HeLa cells transfected with siControl or siCyclin B2. After 36 h of transfection, cells were treated with nocodazole for 2 h. Then cells were fixed and co-stained fo Cdc20 (green) in D, ACA (red), and DNA (blue) E) Representative immunofluorescence images of HeLa cells co-transfected with siCyclin B2 plus GFP-tagged Cyclin B2-WT or Cyclin B2-4A. At 36 h post-transfection, cells were treated with nocodazole for 2 h. Then cells were fixed and co-stained fo Cdc20 (red) in E, and DNA (blue)",
    "ncbi_link": "GFP: 
Cyclin B2: 9133"
  },
  {
    "caption": "(H) Immunoprecipitation assay performed with Cdc20 antibody. HeLa cells were transfected with siControl or siCyclin B2. At 36 h after transfection, cells were arrested in mitosis, collected, and lysed. Cell lysates were incubated with Protein A/G beads bound with Cdc20 antibody. Following extensive washes, immunoprecipitates were resolved by SAS-PAGE and analyzed by Western blotting using anti-Cdc20, anti-BubR1, anti-Bub3, and anti-Mad2 antibodies",
    "ncbi_link": "Cyclin B2: 9133"
  },
  {
    "caption": "A Northern blots comparing GlmY and GlmZ levels in wild type strain Z8 and the ∆rapZ mutant Z28 under normal growth and GlcN6P starvation conditions. Both strains, which also carried a chromosomal glmS'-lacZ fusion, were treated with 60 μg/ml Nva-FMDP or H2O (\"mock\"). Samples were harvested hourly for Northern analysis and determination of β-galactosidase activity. Growth curves are shown in Appendix Fig S1. Blots were re-probed using a 5S rRNA specific probe to provide loading controls.",
    "ncbi_link": "5S rRNA: 
glmS: 948241
GlmY: 2847700
GlmZ: 2847678
lacZ: 945006
rapZ: 947727"
  },
  {
    "caption": "B The purification profile of Strep-RapZ from the ∆glmS strain Z904 under GlcN6P replete and depletion conditions is shown (top). The cleared lysate (CL), flow through (FT), washing steps (W) and the elution fractions (E1-3) from StrepTactin affinity chromatography were separated on 12.5 % SDS-PAA gels and stained with Coomassie blue. Metabolites were extracted from E2 and analyzed by HILIC-MS/MS. The extracted ion chromatograms of the LC-MS analysis targeting GlcN6P (retention time 16.6 minutes) are shown below. The samples derived from purification of Strep-RapZ (panels i and ii) or Strep-KdpE (panels iii and iv) were analyzed with the SRM transition m/z 258.1 to m/z 97 in the negative ion mode. The identity of the metabolite detected in panel i was confirmed by adding chemically pure GlcN6P to a final concentration of 100 pg/μl (panel v).",
    "ncbi_link": "glmS: 948241"
  },
  {
    "caption": "Reporter gene assays addressing expression of lacZ fusions under GlcN6P replete and depletion conditions. strains were grown in 96-well plates and exposed to various degrees of GlcN6P depletion elicited by Nva-FMDP. Cells were harvested at indicated times and the β-galactosidase activities were determined. Strains Z197 and Z360 were used, which harbor glmY'-lacZ and glmZ'-lacZ fusions, respectively.",
    "ncbi_link": "glmY: 2847700
glmZ: 2847678
lacZ: 945006"
  },
  {
    "caption": "Reporter gene assays addressing expression of lacZ fusions under GlcN6P replete and depletion conditions. strains were grown in 96-well plates and exposed to various degrees of GlcN6P depletion elicited by Nva-FMDP. Cells were harvested at indicated times and the β-galactosidase activities were determined. Expression of glmY'-lacZ in strain Z197 and the ∆rapZ mutant Z225 is compared.",
    "ncbi_link": "glmY: 2847700
lacZ: 945006
rapZ: 947727"
  },
  {
    "caption": "Reporter gene assays addressing expression of lacZ fusions under GlcN6P replete and depletion conditions. strains were grown in 96-well plates and exposed to various degrees of GlcN6P depletion elicited by Nva-FMDP. Cells were harvested at indicated times and the β-galactosidase activities were determined. Strains Z190 and Z201 were addressed, which transcribe glmY'-lacZ either from the σ54-promoter or the σ70 promoter, respectively.",
    "ncbi_link": "glmY: 2847700
lacZ: 945006"
  },
  {
    "caption": "Reporter gene assays addressing expression of lacZ fusions under GlcN6P replete and depletion conditions. strains were grown in 96-well plates and exposed to various degrees of GlcN6P depletion elicited by Nva-FMDP. Cells were harvested at indicated times and the β-galactosidase activities were determined. Strains Z190 and the ∆qseF mutant Z196 are compared, both of which transcribe the glmY'-lacZ fusion solely from the σ54 promoter.",
    "ncbi_link": "glmY: 2847700
qseF: 947042
lacZ: 945006"
  },
  {
    "caption": "Reporter gene assays addressing expression of lacZ fusions under GlcN6P replete and depletion conditions. strains were grown in 96-well plates and exposed to various degrees of GlcN6P depletion elicited by Nva-FMDP. Cells were harvested at indicated times and the β-galactosidase activities were determined. Complementation experiment analyzing the requirement of rapZ for glmY expression in cells grown to exponential phase under standard conditions in flask cultures. Strains Z197 and the ∆rapZ mutant Z225 were used. Tested plasmids were pFDX4291 (vector control for pFDX4324 and pYG82 = VC1), pFDX4324 (rapZ), pYG82 (rapZquad), pBGG237 (vector control for pBGG164 = VC2) and pBGG164 (strep-rapZ).",
    "ncbi_link": "strep: 
glmY: 2847700
lacZ: 945006
rapZ: 947727"
  },
  {
    "caption": "C To assess the role of RapZ for QseF activity, β-galactosidase activities were determined from strains Z196 (∆qseF) and Z1110 (∆qseF ∆rapZ) at indicated times during growth. Strains harbored the glmY'-lacZ fusion that is solely expressed from the σ54 promoter and the following plasmids: pKESK23 (VC = vector control; black and grey; note that activities are too low for display), pYG89 (qseF, green), pYG90 (qseF-D56E, purple), pYG93 (qseF-D56A, red). , β-galactosidase activities are presented as mean ± SD.",
    "ncbi_link": "lacZ: 
glmY: 2847700
qseF: 947042
QseF: 947042
RapZ: 947727
rapZ: 947727"
  },
  {
    "caption": "E Analysis of QseE' autophosphorylation (lanes 1-6) and phosphoryl group transfer to QseF (lanes 7-12) in absence or presence of 5 μM Strep-RapZ. To assess phosphoryl group transfer, 1 μM QseF-His10 was added to the assay.",
    "ncbi_link": "His10: "
  },
  {
    "caption": "A β-Galactosidase activities of strains Z197 (wild type) and Z1118 (∆glmY ∆glmZ), which carry the chromosomal glmY'-lacZ fusion, were determined during growth.",
    "ncbi_link": "lacZ: 
glmY: 2847700
glmZ: 2847678"
  },
  {
    "caption": "B Strains Z197 (wild type) and Z225 (∆rapZ) were transformed with the following plasmids expressing the mentioned sRNAs: pBR-plac (vector control = VC), pYG83 (glmY), pYG84 (glmZ) and pSD69 (gcvB). sRNA expression was induced with 1 mM IPTG and β-galactosidase activities were determined in the exponential growth phase.",
    "ncbi_link": "gcvB: 2847720
glmY: 2847700
glmZ: 2847678
rapZ: 947727"
  },
  {
    "caption": "C To assess the impact of GlmY* and GlmZ on stimulation of QseE' autophosphorylation by RapZ, 1 μM QseE'-His10 was incubated with [γ-32P]-ATP in absence or presence of 5 μM Strep-RapZ and/or the sRNAs GlmY*, GlmZ and GcvB. In lanes 3-11 QseE' was co-incubated with RapZ as well as the indicated sRNAs provided at 0.5 μM, 1.25 μM and 2.5 μM. In lanes 14-16, QseE' was incubated with 2.5 μM of each sRNA without RapZ. Samples were removed 1 min after addition of [γ-32P]-ATP and separated on 12.5 % SDS-PAA gels, which were analyzed by phospho imaging.",
    "ncbi_link": "GcvB: 2847720
GlmY: 2847700
GlmY*: 2847700
GlmZ: 2847678"
  },
  {
    "caption": "Northern blot experiments assessing the half-lives of GlmY* and GlmZ under normal growth and GlcN6P starvation conditions. Bacterial cultures were either treated with 100 μg/ml Nva-FMDP or H2O (mock). Transcription was stopped by rifampicin addition when cultures attained OD600 = 1.0 and samples were removed at indicated times for Northern analysis. A Analysis of GlmY* and GlmZ decay in the wild type strain Z8. B Analysis of GlmY* and GlmZ decay in the ∆rapZ mutant Z28. C Semi-logarithmic plots of GlmY* and full-length GlmZ decay for half-life determination. ",
    "ncbi_link": "GlmY: 2847700
GlmZ: 2847678
rapZ: 947727"
  },
  {
    "caption": "Northern blot experiments (A-C) assessing GlmY* half-life under GlcN6P replete (+GlcN) and depletion conditions (-GlcN). Transcription was stopped by addition of rifampicin and samples were harvested at indicated times for Northern analysis. A Analysis of the ∆glmS strain Z1126. The GlcN6P depleted culture was split 8 min after rifampicin addition and one of the sub-cultures was resupplied with GlcN (indicated by arrow). B The ∆glmS ∆rapZ double mutant Z1127 was tested. C Semi-logarithmic plots of GlmY* decay for half-life determination. ",
    "ncbi_link": "glmS: 948241
GlmY: 2847700
rapZ: 947727"
  },
  {
    "caption": "D EMSA experiments addressing the role of GlcN6P for GlmY*/RapZ interaction. Radiolabelled GlmY* was incubated with incremental concentrations of RapZ (left panel) or RapZ-CTD (right panel) in absence or presence of 7.5 mM GlcN6P. Binding reactions were separated on native PAA gels and analyzed by phospho-imaging. The RapZ/GlmY* complex is indicated by an arrow.",
    "ncbi_link": "GlmY: 2847700"
  },
  {
    "caption": "E EMSA following incubation of GlmY* with 1200 nM RapZ in presence of various GlcN6P concentrations ranging from 0 (lane 2) to 8 mM (lane 10). The fraction of GlmY* remaining in the gel pocket is marked with an asterisk. The RapZ/GlmY* complex is indicated by an arrow.",
    "ncbi_link": "GlmY: 2847700"
  },
  {
    "caption": "F EMSA following incubation of GlmY* with 1200 nM RapZ in absence or presence of 7.5 mM of the indicated metabolite. The RapZ/GlmY* complex is indicated by an arrow.",
    "ncbi_link": "GlmY: 2847700"
  },
  {
    "caption": "(B) RNA samples extracted from normal breast epithelial cell, MCF10A, and different subtypes of breast cancer cell lines as indicated were subjected to RT-qPCR analysis to examine the expression of circPVT1 (n = 3 biological replicates, ±s.e.m., ns: non-significant, *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(C) RNA samples extracted from 28 pairs of ER-positive (ER+) breast tumor and adjacent normal tissues and 14 pairs of ER-negative (ER-) breast tumor and adjacent normal tissues were subjected to RT-qPCR analysis to examine the expression of circPVT1 (±s.e.m., *P < 0.05, **P < 0.01 by two-tailed Student's t-test).",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells were infected with control shRNA (sh-CTL) or two independent shRNAs specifically targeting circPVT1 (sh-circPVT1#1 and sh-circPVT1#2) were subjected to RNA extraction and RT-qPCR analysis to examine the expression of circPVT1 (H) (n = 3 biological replicates, ± s.e.m., ***P < 0. 001 by two-tailed Student's t-test).",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells were infected with control shRNA (sh-CTL) or two independent shRNAs specifically targeting circPVT1 (sh-circPVT1#1 and sh-circPVT1#2) were subjected to colony formation assay (I) (n = 3 biological replicates, ± s.e.m., ***P < 0. 001 by two-tailed Student's t-test). (J) Quantification of the crystal violet dye as shown in (I) (n = 3 biological replicates, ± s.e.m., ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(O) Tamoxifen-resistant MCF7 cells transfected with si-CTL, si-circPVT1#1, or si-circPVT1#2 were treated with or without tamoxifen (Tam, 5 μM, 72 h) followed by cell proliferation assay",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(B) Total RNAs extracted from MCF7 cells were incubated with or without RNase R (10 units/μg RNA) at 37℃ for duration as indicated, followed by RT-qPCR analysis to examine the expression of PVT1 or circPVT1 (C) MCF7 cells were treated with Actinomycin D (10 g/ml) for duration as indicated, followed by RT-qPCR analysis to examine the expression of PVT1 or circPVT1",
    "ncbi_link": "circPVT1: 5820
PVT1: 5820"
  },
  {
    "caption": "(F) MCF7 cells were subjected to cellular fractionation followed by RNA extraction and RT-qPCR analysis to quantify the amount of circRNA in both nucleus and cytosol of the cells. ACTIN and U6 snoRNA were served as purity control for cytosolic and nuclear fractions, respectively (n = 3 biological replicates, ± s.e.m.).",
    "ncbi_link": "U6 snoRNA: 
ACTIN: 60"
  },
  {
    "caption": "(G) MCF7 cells transfected with si-CTL, si-circPVT1#1, or si-circPVT1#2 were subjected to RNA-FISH analysis using probe specifically targeting circPVT1. Red: circPVT1; Blue: DAPI.",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(D, E) UCSC genome browser views of RNA-seq as described in (A) for TFF1 (D) and GREB1 (E) are shown.",
    "ncbi_link": "GREB1: 9687
TFF1: 7031"
  },
  {
    "caption": "(F) MCF7 cells transfected with si-CTL, si-circPVT1#1, or si-circPVT1#2 were treated with or without estrogen (E2, 10-7 M, 6 h) followed by RNA extraction and RT-qPCR analysis to examine the expression of genes as indicated (G) MCF7 cells infected with sh-CTL, sh-circPVT1#1, or sh-circPVT1#2 were treated with or without estrogen (E2, 10-7 M, 6 h) followed by RNA extraction and RT-qPCR analysis to examine the expression of genes as indicated",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with control siRNA (si-CTL) or siRNAs specifically targeting circPVT1 (si-circPVT1#1 and si-circPVT1#2) were treated with or without estrogen (E2, 10-7 M, 6 h) followed by immunoblotting analysis (D) to examine the expression of ERα",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(E) Tumor samples as described in Fig 1K were subjected to RNA extraction and RT-qPCR analysis to examine the expression of ESR1 (n = 6 biological replicates, ±s.e.m., ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "ESR1: 2099"
  },
  {
    "caption": "(H) Wild-type circPVT1-luc (circPVT1-luc (WT)) and its mutant form with the potential miR-181a-2-3p or miR-6715b-5p binding site mutated (circPVT1 (MT)-luc) were transfected into HEK293T cells with or without CTL, miR-181a-2-3p, or miR-6715b-5p mimic followed by luciferase activity measurement (n = 3 biological replicates, ±s.e.m., ns: non-significant, **P < 0.01 by two-tailed Student's t-test).",
    "ncbi_link": "luc: 
miR-181a-2-3p: 406954
miR-6715b-5p: 102465427
circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with si-CTL or si-circPVT1 in the presence or absence of miR-181a-2-3p inhibitor were subjected to RT-qPCR analysis using antibodies as indicated (n = 3 biological replicates, ±s.e.m., **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "miR-181a-2-3p: 406954
circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with si-CTL or si-circPVT1 in the presence or absence of miR-181a-2-3p inhibitor to examine the expression of genes as indicated and immunoblotting analysis (M) using antibodies as indicated",
    "ncbi_link": "miR-181a-2-3p: 406954
circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with si-CTL or si-circPVT1 in the presence or absence of miR-181a-2-3p inhibitor were subjected to RT-qPCR analysis using antibodies as indicated (n = 3 biological replicates, ±s.e.m., **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "miR-181a-2-3p: 406954
circPVT1: 5820"
  },
  {
    "caption": "(P) MCF7 cells were infected with control shRNA (sh-CTL) or shRNAs specifically targeting circPVT1 (sh-circPVT1) in the presence or absence of miR-181a-2-3p inhibitor were subjected to colony formation assay. (Q) Quantification of the crystal violet dye as shown in (P) (n = 3 biological replicates, ± s.e.m., **P < 0.01 by two-tailed Student's t-test).",
    "ncbi_link": "miR-181a-2-3p: 406954
circPVT1: 5820"
  },
  {
    "caption": "(A) MCF7 cells infected with control shRNA (sh-CTL) or shRNAs specifically targeting MAVS (sh-MAVS) or STING (sh-MAVS) were transfected with control siRNA (si-CTL) or siRNA specifically targeting circPVT1 (si-circPVT1) followed by RT-qPCR analysis to examine the expression of genes as indicated (n = 3 biological replicates, ±s.e.m., ns: non-significant, *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "STING: 
MAVS: 57506
circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells infected with sh-CTL, sh-MAVS, sh-MDA5, or sh-RIGI were transfected with si-CTL or si-circPVT1 followed by using antibodies as indicated and RT-qPCR analysis (C) to examine the expression of genes as indicated (n = 3 biological replicates, ±s.e.m., ns: non-significant, *P < 0.05, **P < 0.01, ***P < 0.001 by two-tailed Student's t-test).",
    "ncbi_link": "MDA5: 
MAVS: 57506
circPVT1: 5820
RIGI: 23586"
  },
  {
    "caption": "HEK293T cells transfected with HA-tagged MAVS-FL, MAVS-NTD, or MAVS-CTD were subjected to RIP using anti-HA antibody followed by immunoblotting analysis(K) using antibodies as indicated",
    "ncbi_link": "HA: 
MAVS: 57506"
  },
  {
    "caption": "(L) HEK293T cells transfected with HA-tagged MAVS and Flag-tagged RIGI in the presence or absence of circPVT1 were subjected to immunoprecipitation (IP) with anti-Flag M2 agarose followed by immunoblotting analysis using antibodies as indicated.",
    "ncbi_link": "Flag: 
HA: 
MAVS: 57506
circPVT1: 5820
RIGI: 23586"
  },
  {
    "caption": "MCF7 cells transfected with control ASO (ASO-CTL) or ASO specifically targeting circPVT1 (ASO-circPVT1) were subjected to RT-qPCR analysis to examine the expression of genes as indicated",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with control ASO (ASO-CTL) or ASO specifically targeting circPVT1 (ASO-circPVT1) were subjected immunoblotting analysis E) using antibodies as indicated",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "MCF7 cells transfected with control ASO (ASO-CTL) or ASO specifically targeting circPVT1 (ASO-circPVT1) were subjected to RT-qPCR analysis to examine the expression of genes as indicated",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "(I, J) MCF7 cells were treated with ASO-CTL, ASO-circPVT1 (50 nM), or fulvestrant (ICI, 1 μM) for duration as indicated followed by cell proliferation assay (I) and colony formation (J) (n = 3 biological replicates, ± s.e.m., **p < 0.01, ***p < 0.001, day 4 by two-tailed Student's t-test).",
    "ncbi_link": "circPVT1: 5820"
  },
  {
    "caption": "E. HeLa cells expressing Arf1-HA were serum starved overnight (E, top) and subsequently stimulated with EGF for 5 min (E, bottom) prior to fixation with PFA. Fixed cells were stained for Arf1 (HA; green) and GIV (red) and nuclei (DAPI; blue). Panels on the left show overlay of all 3 stains and representative RGB plots of sections through the Arf1-stained pixels. Panels on the right display the magnified 3D surface plots of the boxed regions in the left panels. Scale bar = 10 µm.",
    "ncbi_link": "HA: 
Arf1: 375"
  },
  {
    "caption": "C. Equal aliquots (~45 µg) of whole cell lysates of control (shControl; top) and GIV-GEM depleted (shGIV; bottom) HeLa cells were analyzed for GIV and tubulin (loading control) by immunoblotting (IB).",
    "ncbi_link": "GIV: 55704"
  },
  {
    "caption": "D. Control (sh Control; top) and GIV-GEM depleted (shGIV; bottom) HeLa cells were co-transfected with Gαi1-YFP, Gβ1-CFP and Gγ2 (untagged) and live cells were analyzed by FRET imaging at steady-state, after being serum starved in 0.2% FBS overnight and then after stimulation with 50 nM EGF. Representative freeze-frame FRET images are shown. FRET image panels display intensities of acceptor emission due to efficient energy transfer in each pixel. FRET scale is shown in the inset. Golgi and PM regions of interest are indicated with arrows. Scale bar = 10 µm. See also Figure EV2A-B for free-frame images for additional time points in control HeLa cells.",
    "ncbi_link": "CFP: 
YFP: 
GIV: 55704
Gαi1: 2770
Gβ1: 2782
Gγ2: 54331"
  },
  {
    "caption": "I. Immunoblot shows bound Arf1 (active; top) and total Arf1 (input lysates; bottom) from equal aliquots of lysates of control (sh Control) and GIV-depleted (shGIV) HeLa cells. Cells were stimulated with EGF for the indicated time points prior to lysis. Bar graphs in Figure EV2E display the fold change in Arf1 activity normalized to t0 min. 'Low' and 'high' indicate exposures.",
    "ncbi_link": "GIV: 55704"
  },
  {
    "caption": "C. Left: Graph displays experimentally determined secretion of GFP-MMP9 in response to varying doses of EGF in control (shControl) and GIV-depleted (shGIV) HeLa cells (as in B), and quantified by band densitometry. Results are expressed as mean ± S.E.M; n = 3 biological replicates. p values were determined by two-sided unpaired t-test. Right: Schematic diagram of dose responses (mG* and secretion) for the single switch and coupled switches. Coupled switches stretch the range of proportionate responses. Single mG switch results in misaligned responses. DoRA, dose response alignment.",
    "ncbi_link": "GIV: 55704"
  },
  {
    "caption": "G-H. Control (parental) and GIV-depleted (GIV KO) HeLa cells grown in different concentrations of serum (FBS%) were treated or not with varying concentrations of BFA (µM) as indicated. Line graphs in 3D (G) depict the formazan absorbance expressed as a measure of cell viability from the HeLa cells in various conditions tested. Bar graphs (H) depict the cell number in serum-free growth conditions that are supported exclusively by autocrine secrete-and-sense loop (without BFA; BFA = 0.0 µM) or when such loop is interrupted (BFA = 0.1 µM). Results are expressed as mean ± S.E.M; n = 3 biological replicates. Statistical significance was determined by one way ANOVA.",
    "ncbi_link": "GIV: 55704"
  },
  {
    "caption": "I-K. Control (parental) and GIV-depleted (GIV KO) MDA MB-231 cells grown in different concentrations of serum (FBS%) were treated or not with varying concentrations of BFA (µM) as in G-H. Line graphs in 3D (I) depict the formazan absorbance expressed as a measure of cell viability from the MDA MB-231 cells in various conditions tested. Bar graphs (J) depict the viability of the MDA MB-231 cells in serum-free growth conditions that are supported exclusively by autocrine secrete-and-sense loop (without BFA; BFA = 0.0 µM) or when such loop is interrupted (BFA = 0.1 µM). Results are expressed as mean ± S.E.M; n = 3 biological replicates. Statistical significance was determined by one way ANOVA. Immunoblots (K) of equal aliquots of whole cell lysates confirm the depletion of GIV compared to tubulin (loading control). See also Appendix Figure S5D-H for dot plots and early and late apoptotic fractions. Results are expressed as mean ± S.E.M; n = 3 biological replicates.",
    "ncbi_link": "GIV: 55704"
  },
  {
    "caption": "Double immunolabeling of PDS5A (green, A-E) and SYCP3 (red) in Pds5AB cKO spread spermatocytes at the indicated stages.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of PDS5B (green, F-J) and SYCP3 (red) in Pds5AB cKO spread spermatocytes at the indicated stages.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "A-H Double immunolabeling of SYCP1 (green) and SYCP3 (red) in wild-type (A-D) and Pds5AB cKO (E-H) spread spermatocytes at the indicated stages. I-L Double immunolabeling of HORMAD2 (pseudocolored in white) and SYCP3 (red). Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm. ",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and the cohesin subunits SMC3 (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and the cohesin subunits REC8 (green in Pds5AB cKO spread spermatocytes at the indicated stages. Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and the cohesin subunits SMC1β (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and the cohesin cofactors Sororin (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and the cohesin cofactors WAPL (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and either γH2AX (pseudocolored in blue in Pds5AB cKO spread spermatocytes at the indicated stages.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAD51 (green in Pds5AB cKO spread spermatocytes at the indicated stages. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "J-L Double immunolabeling of MLH1 (pseudocolored in white) and SYCP3 (red) in Pds5AB cKO spread spermatocytes. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and TRF1 (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAP1 (green, in Pds5AB cKO spread spermatocytes at the indicated stages. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "I Selected zygotene-like and pachytene-like bivalents presenting altered TRF1 distribution as (from left to right) (i) telomere stretches, (ii) multiple telomere, (iii) distant telomeres and (iv) telomere-less. Arrowheads in (I) indicate the position of altered telomeres. J Quantification of telomeres with a regular or altered disposition of TRF1 in Pds5AB cKO spermatocytes at the indicated stages (n=1646 telomeres in zygotene-like spermatocytes and 738 in pachytene-like ones). Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "M-P Double immunolabeling of SUN1 (green) and SYCP3 (red) in Pds5AB cKO spread spermatocytes at the indicated stages. 0, 1 and 2 in (N and O) indicate the number of chromosome ends labelled by SUN1 in a given bivalent. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "R Selected zygotene-like and early pachytene-like bivalents from Pds5AB cKO spermatocytes immunolabeled with SYCP3 (red) and SUN1 (green), and their respective percentage of appearance. S Quantification of telomeres with a regular or altered disposition of SUN1 (n=715 telomeres in zygotene-like spermatocytes and 410 in pachytene-like ones). Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "A-C Immunolabeling of SYCP3 (red) and telomere FISH (PNA-Tel, green) in Pds5AB cKO spread spermatocytes at the indicated stages. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "D 300% magnification of selected zygotene-like and pachytene-like bivalents presenting regular (left) or altered (i-iv) telomere FISH signals. E Quantification of telomeres with a regular or altered disposition of telomeric DNA in Pds5AB cKO spermatocytes at the indicated stages (n=1198 telomeres in zygotene-like spermatocytes and 574 in pachytene-like ones).",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAP1 (blue) and telomere FISH (PNA-Tel, green) in Pds5AB cKO spread spermatocytesat the indicated stages. Asterisks indicate the position of the enlarged chromosomes/bivalents shown in a 300% magnification displaying telomere stretches, multiple telomere, distant telomeres and telomere-less. Yellow arrowheads in (I) indicate telomeres displaying a distant telomere configuration observed both by telomere FISH and RAP1 immunolabeling. White arrowheads indicate telomeres with an altered organization of telomeric DNA into multiple telomere signals without RAP1 signals Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAP1 (blue) and telomere FISH (PNA-Tel, green) in Pds5AB cKO spread spermatocytes at the indicated stages. Asterisks indicate the position of the enlarged chromosomes/bivalents shown in a 300% magnification displaying telomere stretches, multiple telomere, distant telomeres and telomere-less. White arrowheads indicate telomeres with an altered organization of telomeric DNA into multiple telomere signals with RAP1 signals and telomere stretches Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAP1 (blue) and telomere FISH (PNA-Tel, green) in Pds5AB cKO spread spermatocytes at the indicated stages. Asterisks indicate the position of the enlarged chromosomes/bivalents shown in a 300% magnification displaying telomere stretches, multiple telomere, distant telomeres and telomere-less. White arrowheads indicate telomeres with an altered organization of telomeric DNA into multiple telomere signals without RAP1 signals telomere stretches Pink arrowheads in (T) indicate a telomere presenting a regular telomere FISH signal without a RAP1 signal. Data information: Sex bivalents (XY) are indicated. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of SYCP3 (red) and RAP1 (blue) and telomere FISH (PNA-Tel, green) in Pds5AB cKO spread spermatocytes at the indicated stages. Asterisks indicate the position of the enlarged chromosomes/bivalents shown in a 300% magnification displaying telomere stretches, multiple telomere, distant telomeres and telomere-less.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of TRF1 (green) and SYCP3 (red) in squashed spermatocytes from wild-type or Pds5AB cKO mice M-P). The first three columns correspond to z-projections of 15 focal planes throughout the Top, Equator and Bottom regions of the nucleus. The projection of 65 focal planes across the same spermatocyte nucleus is shown at the fourth column (Z-Projection). White arrowheads in (F indicate the presence of TRF1 signals non-attached to the NE. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Double immunolabeling of TRF1 (green) and SYCP3 (red) in squashed spermatocytes from wild-type or Pds5AB cKO mice The first three columns correspond to z-projections of 15 focal planes throughout the Top, Equator and Bottom regions of the nucleus. The projection of 65 focal planes across the same spermatocyte nucleus is shown at the fourth column (Z-Projection). White arrowheads in N) indicate the presence of TRF1 signals non-attached to the NE. Scale bar, 10 μm.",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "Q-T Selected bivalents from Pds5AB cKO spermatocytes displaying structural telomere abnormalities as telomere stretches (Q), multiple telomere (R), distant telomere (S) and telomere-less (T).",
    "ncbi_link": "Pds5A: 71521"
  },
  {
    "caption": "(B-E) Co-localization of EGFP and the two CA isoforms with filamentous actin studied in fibroblasts expressing (B) EGFP, (C) EGFP-CA2, or (D, E) EGFP-CA7 and stained with phalloidin-594 to visualize F-actin (n = 4, 10 and 8 independent replicates, respectively). A magnification of the area marked with the yellow rectangle in (C) and (D) shows the localization of EGFP-CA2 and EGFP-CA7 compared to phalloidin-594. (E) EGFP-CA7 caused a prominent overexpression phenotype with thick and curvy cytosolic actin bundles (arrow) and plasmalemmal protrusions (arrowhead).",
    "ncbi_link": "CA2: 12349
CA7: 12354"
  },
  {
    "caption": "(A,B) NIH3T3 cells transfected with DsRed (A) or DsRed-CA7 (B) were incubated in growth medium with 5 µM Latrunculin B for 0, 2, 5, 10, or 30 minutes, or in an equal amount of DMSO for 60 minutes. Analyses of experiments show that in cells transfected with DsRed-CA7 F-actin structures collapse more slowly (0 min: 83% \"normal\"; 2 min: 80%, p = 0.44; 5 min: 74%, p = 0.39; 10 min: 27%, p = 0.08; 30 min: 16%, p = 0.02; DMSO: 82%, p = 0.99; tested against 0 min with two-way ANOVA, Dunnett's multiple comparison test) than in the DsRed-transfected ones (0 min: 89% \"normal\"; 2 min: 48%, p = 0.14; 5 min: 31%, p = 0.04; 10 min: 2%, p = 0.001; 30 min: 0.7%, p = 0.001; DMSO: 88%, p = 0.8; tested against 0 min with two-way ANOVA, Dunnett's multiple comparison test) . For the analysis, cells were categorized to three groups as \"normal\", \"some shape/F-actin left\" and \"round\". The upper panel shows example images of the cells in all three categories for (A) DsRed- or (B) DsRed-CA7 transfected cells (actin visualized with Phalloidin-488).",
    "ncbi_link": "DsRed: 
CA7: 12354"
  },
  {
    "caption": "(E) Pearson's correlation coefficient values calculated for the depicted constructs and compared to CA7. F-actin had a strong positive correlation coefficient with EGFP-CA7 (r = 0.91 ± 0.02, n = 26 cells). Neither EGFP alone (r = 0.01 ± 0.03, n = 56) nor EGFP-CA2 (r = 0.09 ± 0.03, n = 53) co-localized with F-actin (P < 0.0001 for both constructs, when compared to CA7). From the five mutated CA7 constructs, EGFP-CA7-mutant1 (r= 0.51 ± 0.04, P < 0.0001, n = 25) and EGFP-CA7-mutant3 (r = 0.72 ± 0.03, P = 0.05, n = 21) co-localized less with F-actin actin when compared to CA7. The co-localization of the other four mutated CA7 constructs, EGFP-CA7-mutant2 (r = 0.92 ± 0.02, P = 0.99, n = 18), EGFP-CA7-R223E (r = 0.86 ± 0.02, P = 0.99, n = 24) and EGFP-CA7-H96/98C (r = 0.79 ± 0.04, P = 0.14, n = 18) did not differ significantly from that of CA7. Data are shown as mean ± SEM. Data did not pass Shapiro-Wilk test for normality, statistical comparison against CA7 was done with Kruskall-Wallis test corrected for multiple comparisons.",
    "ncbi_link": "EGFP: 
CA2: 12349
CA7: 12354"
  },
  {
    "caption": "(B,C) Representative confocal images of precocious in vivo expression of (B) EGFP-CA2 and (C) EGFP-CA7 in P40 mouse cortical layer 2/3 pyramidal neurons. Neurons were transfected at E14.5 with EGFP-CA2 or EGFP-CA7 using in utero electroporation and images were taken from fixed slices. Right panels in (B) and (C) show higher magnification of the primary apical dendrite marked with a box. (D) The expression of EGFP-CA7 disrupted the normal spine morphology and induced the formation of thick, filopodia-like protrusions. ",
    "ncbi_link": "EGFP: 
CA2: 12349
CA7: 12354"
  },
  {
    "caption": "(A) Comparison of mEPSCs in cortical layer 2/3 pyramidal neurons from P30 - P40 WT and CA7 KO mice. Sample traces of mEPSC recordings from WT and CA7 KO neurons, low-pas filtered at 1 kHz (left). The data are summarized in the bar diagrams (right). mEPSC frequency (P = 0.63) and amplitude (P = 0.90) were not significantly different between WT and CA7 KO and neurons (n = 7 and 5 neurons, respectively, Student's independent samples t-test).",
    "ncbi_link": "CA7: 12354"
  },
  {
    "caption": "(B) Representative confocal images of apical dendrites from Lucifer Yellow injected cortical layer 2/3 pyramidal neurons from WT and CA7 KO mice. The dendritic spine density and spine head size were examined in fixed slice preparations from P34 - P37 mice. Scale bar 2 µm.",
    "ncbi_link": "CA7: 12354"
  },
  {
    "caption": "(C) Summary of the spine density analysis done from the Lucifer Yellow injected neurons. Spine density was a higher in CA7 KO neurons both in apical and basal dendrites (n = 28 neurons for both) compared to WT (n= 29 neurons for apical and n=30 for basal dendrite analysis) (P = 0.000002 for apical dendrites, analyzed with Mann-Whitney test, and P = 6,8 x 10-8 for basal dendrites, Student's t-test with Welch-correction.) A total of 8279 spines were analyzed from four CA7 KO mice and 8730 spines from two WT control mice.",
    "ncbi_link": "CA7: 12354"
  },
  {
    "caption": "(D) The spine head width distribution7differed significantly between the genotypes (n= 467 spines from WT and n = 421 spines from CA7 KO animals, 15 neurons analyzed from both genotypes, Wilcoxon rank sum test with continuity correction, W = 134540, P < 0.001).",
    "ncbi_link": "CA7: 12354"
  },
  {
    "caption": "A) Volcano plot of proteome analysis. Plotted is the negative log10 of the p-value (y-axis) versus the log2 LFQ ratio of SPPL2c overexpressing and control cells (x-axis) of a given identified protein. A permutation based FDR correction for multiple hypotheses was applied (p = 0.05; s0 = 0.1; dashed line). Open grey circles indicate proteins not-significantly altered in SPPL2c expressing cells, red circles significantly altered proteins after FDR correction. Filled red circles indicate type IV membrane proteins and filled blue circles with red line and blue names type II proteins altered in SPPL2c expressing cells, n=6 biological repl. per cell line.",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "C) Western Blot of selected type IV SPPL2c candidate substrates. Endogenous protein levels of VAPA, VAPB, VAMP8, Syntaxin 8, 18 (Stx8 & Stx18) and Membrin (encoded by the gene Golgi SNAP Receptor Complex Member 2, GOSR2) were analyzed in HEK293 cells ectopically expressing wild type SPPL2c (SPPL2c WT) or a catalytically inactive SPPL2c (SPPL2c D/A). Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as controls. VAPA, VAPB, VAMP8, Stx8 and Membrin protein levels were decreased in SPPL2c expressing cells but not in control or SPPL2c D/A expressing cells. For Stx18 a cleavage product was detected in SPPL2c WT expressing cells. Expression levels of SPPL2c are depicted and Calnexin serves as loading control.",
    "ncbi_link": "Golgi SNAP Receptor Complex Member 2: 9570
GOSR2: 9570
SPPL2c: 162540"
  },
  {
    "caption": "A) SPPL2c overexpression causes a decrease on SPPL3 levels. Endogenous levels of SPPL3 were assessed in cells ectopically expressing wild type SPPL2c (SPPL2c WT) or catalytically inactive SPPL2c (SPPL2c D/A) by Western Blot. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as controls. Note that SPPL3 expression is reduced in cells expressing SPPL2c wt. Data information: Expression levels of the ectopically expressed SPPL proteases are shown and Calnexin serves as loading control",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "B) SPPL2c impairs secretion and maturation of glycan-modifying enzymes. Protein levels of endogenous EXTL3, B4GALT1, OGFOD3 and GnT-V were monitored in lysates of cells treated with control siRNA (siCtr) or with siRNA targeting SPPL3 (siSPPL3) and in cells ectopically expressing either SPPL2c or SPPL3 by Western Blot. In addition, the secreted forms (sEXTL3, sB4GALT1, sOGFOD3, sGnTV,) were analyzed in the corresponding conditioned media using Western Blot. Note that SPPL2c reduces secretion of the glycosyltransferases similar to SPPL3 knock down, but additionally induces a decrease of the mature glycosyltransferases in the cell lysate similar to ectopic expression of SPPL3. Data information: Expression levels of the ectopically expressed SPPL proteases are shown and Calnexin serves as loading control",
    "ncbi_link": "SPPL2c: 162540
SPPL3: 121665"
  },
  {
    "caption": "C) Processing of ectopically expressed GnT-V with an N-terminal Flag- and C-terminal V5-tag (Flag-GnTV-V5) was analyzed in lysates and conditioned media (sup.) of either SPPL2c wt or SPPL2c D/A expressing cells by Western Blot. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as controls. In addition, maturation of the glycoproteins Nicastrin (NCT), Lamp2 and SPPL2a was monitored by detection of the respective mature (mat) and immature (im) version. Note that secretion of GnT-V is impaired in SPPL2c wt expressing cells and immature glycoproteins accumulate. Data information: Expression levels of the ectopically expressed SPPL proteases are shown and Calnexin serves as loading control",
    "ncbi_link": "Flag: 
V5: 
GnT-V: 4249
GnTV: 4249
SPPL2c: 162540"
  },
  {
    "caption": "D) SPPL2c induces mislocalization of GnT-V. Ectopically expressed GnT-V was visualized by immunofluorescence staining using the anti-V5 antibody either in control cells (Ctr) or in cells co-expressing either SPPL2c wt or SPPL2c D/A. The ER was stained using the anti-BiP antibody and the Golgi with the anti-TGN46 antibody. While in control cells GnT-V mainly localizes to the Golgi, its localization shifts to more ER-like structures in SPPL2c expressing cells. Scale bar 5 µm.",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates VAPA (A) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates VAPB (B) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates VAMP8 (C) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates Syntaxin 8 (Stx8) (D) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates Syntaxin 18 (Stx18) (E) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "Protein levels of the validated SPPL2c substrates Membrin (F) were reduced using specific siRNAs. Non-targeting control siRNA (Ctr) served as negative control and overexpression of SPPL2c WT was used as a positive control. Non-transfected cells (-) or stably transfected but non-induced SPPL2c wt cells (n/i) served as additional controls for antibody specificity. Processing and maturation of ectopically expressed GnT-V and maturation of endogenous SPPL2a were monitored by Western Blotting. None of the substrates' knock down fully recapitulated the effect on GnT-V or on endogenous glycoproteins observed in SPPL2c overexpressing cells. Calnexin served as loading control and ectopic expression of SPPL2c WT and SPPL2c D/A was confirmed using a SPPL2c specific antibody.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540"
  },
  {
    "caption": "B) Processing of endogenous Syntaxin 5 (Stx5) and Syntaxin 6 (Stx6) by SPPL2c wt by Western Blot. Non-transfected cells (-), stably transfected but non-induced SPPL2c wt cells (n/i) and induced cells stably expressing SPPL2c D/A served as controls. Results are derived from one experiment, thus expression (SPPL2c) and loading (Calnexin) control are the same. Note, that Syntaxin 5 is cleaved by SPPL2c while Syntaxin 6 is not.",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "C) Syntaxin 5 protein levels were down regulated and processing and maturation of ectopically expressed GnT-V, as well maturation of the endogenous glycoproteins Nicastrin (NCT) and SPPL2a was analyzed in Western Blot. Calnexin served as loading control and ectopic expression of SPPL2c WT was confirmed using a SPPL2c specific antibody. While GnT-V and Nicastrin maturation were similarly affected by Syntaxin 5 knock down and SPPL2c overexpression, SPPL2a maturation was hardly impaired in Syntaxin 5 knock down cells.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540
Syntaxin 5: 6811"
  },
  {
    "caption": "D) Syntaxin 5 localization is impaired by overexpression of SPPL2c. Endogenous Syntaxin 5 was visualized in control cells without SPPL2c expression (Ctr) and in cells overexpressing SPPL2c wt or SPPL2c D/A using immunofluorescence. BiP was used as a marker protein of the ER and TGN46 as Golgi marker. White arrow indicating cells with disturbed Golgi and Syntaxin 5 staining. Scale bar 5 µm.",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "E) Syntaxin 5 knock down induces mislocalization of GnT-V similar to SPPL2c overexpression Cells ectopically expressing GnT-V were treated either with non-specific siRNA (siCtr) or with siRNA targeting Syntaxin 5 (siStx5). GnT-V was visualized in immunofluorescence using anti-V5 antibody targeting its C-terminal tag and either BIP was co-stained as ER marker protein or TGN46 as Golgi marker protein. Scale bar 5 µm.",
    "ncbi_link": "GnT-V: 4249
SPPL2c: 162540
Stx5: 6811
Syntaxin 5: 6811"
  },
  {
    "caption": "After seeding cells were cultured for 72h and expression of catalytically active (wt) or non-active (D/A) SPPL2c was induced by addition of doxycycline for either 24h or 48h as indicated. Non-transfected cells (Ctr) or non-induced SPPL2c cells (n/i) served as controls. The ER was stained with the anti-BiP antibody, the cis/medial-Golgi with the anti-Giantin, the trans-Golgi Network with the anti-TGN46 antibody and all Golgi subcompartments with the CAB45-specific antibody in immunofluorescence. Note that only upon expression of catalytically active SPPL2c the morphologies of ER and cis-Golgi change compared to controls. Scale bar 5 µm.",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "A) Western Blot analysis of SPPL2c in membrane preparations from HEK293 inducibly overexpressing SPPL2c, human testis and mouse testis tissue. For human and mouse tissue, 5 μg protein of each total testis preparation is loaded. The membrane fraction obtained from a confluent 6 cm dish of SPPL2c expressing HEK293 cells is diluted 1:50 (0.1 μg total protein).",
    "ncbi_link": "SPPL2c: 162540"
  },
  {
    "caption": "C) Analysis of Syntaxin 8 (Stx8) in SPPL2c-/- mice compared to wildtype (wt) littermates. Membrane isolates from whole testis were analyzed for Syntaxin 8 (Stx8) and SPPL2c expression. TMEM192 serves as loading control.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "D) Syntaxin 8 protein levels were quantified from the respective Western blots by densitometric analysis and normalized to those of TMEM192. Bars represent mean values of n=3 animals ± SD normalized to mean Syntaxin 8 levels of wildtype mice. Statistical significance was calculated applying an unpaired, two-sided Student's t-test. * p≤0.05. Note that Syntaxin 8 is accumulating in SPPL2c-/- mice.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "E) Real-time qPCR analysis of Syntaxin 8 (Stx8) mRNA levels in testis of SPPL2c-/- and the wildtype mice normalized to that of Tuba1a. The diagram depicts mean values of Stx8 mRNA levels normalized to that of wildtype animals of n=6 individuals from two independent experiments ± SD. For statistical analysis an unpaired, two-sided Student's t-test was performed. ns = not significant.",
    "ncbi_link": "Tuba1a: 
SPPL2c: 237958
Stx8: 55943
Syntaxin 8: 55943"
  },
  {
    "caption": "F) Immunohistochemical stainings of cross-sectioned seminiferous tubules of SPPL2c+/+ and SPPL2c-/- mice using anti-Cab45 antibody. Stages VII/VIII are depicted. Higher magnifications are indicated with dashed lines and black arrows indicate pre-acrosomal structures. Scale bar 50 µm.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "G) Volcano plot depicting the binding affinities of lectins on sperm lysates from SPPL2c-/- mice compared to SPPL2c+/+ (wt). Each circle represents one lectin. The lectins above the dashed line (light blue) have a significant p-value<0.05. Lectins on the left side of the blot demonstrate reduced binding while UEA-I on the right side has increased binding. n=4 animals per genotype, two-sided, unpaired Student's t-Test.",
    "ncbi_link": "SPPL2c: 237958"
  },
  {
    "caption": "(A) Growth curve of Leishmania promastigotes in HOMEM medium at 26°C. *, Δatg5 differed significantly from WT (p<0.05).",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "(C) Occurrence of GFP-ATG8 puncta in promastigotes when incubated in the conditions detailed in (B). Means ± SD from four independent experiments. * and **, occurrence of GFP-ATG8 puncta in Δatg5 were significantly different from in WT in nutrient-deprived and nutrient-rich conditions (p<0.05).",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "(A) Enlarged (EM) and swollen (WM) mitochondria seen by transmission electron microscopy (TEM) in Δatg5 promastigotes under standard growth conditions. WT is shown at bottom right. Scale bar, 500 nm.",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "(B) Fluorescent intensity from MitoTracker Red (MTR, 0.1 µM) and MitoTracker Green (MTG, 0.2 µM) in 2×106promastigotes after 30 min incubation at 26°C. Values shown are the means ± SD from three independent experiments. * and **, fluorescence was significantly different between WT and Δatg5 (p<0.05).",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "(C) Types of mitochondrial morphology observed by fluorescence microscopy of Δatg5 promastigotes expressing the mitochondrial marker protein MUP-GFP. Scale bar, 10 µm.",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "Phospholipid accumulation in Δatg5 promastigotes.Negative ion survey scans (650-900 m/z) of WT (A) and Δatg5 (B) promastigotes extracted for lipids and analysed by ES-MS, as described in Materials and Methods. a = (alkylacyl).",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "(D) Lesion progression in BALB/c mice inoculated with 5×105 stationary phase promastigotes. Values shown are the means ± SD from 5 mice. *, infection level of Δatg5 differed significantly from WT (p<0.01) and Δatg5::ATG5 (p<0.05).",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "A) SEM analysis of promastigote culture initiated with Δatg5 isolated from a mouse lesion and cultured in nutrient-rich medium. Shown are ovoid and amastigote-like form (left); spindled-shaped form without an external flagellum (centre left panel) and with an external flagellum of varying lengths (centre right and right panels). Scale bar, 10 µm.",
    "ncbi_link": "atg5: 5653628"
  },
  {
    "caption": "B. β-catenin-mediated reporter activity in HEK293T cells expressing the indicated RNF43 cancer mutants. Cells were treated with control medium (no Wnt3a) or Wnt3a-conditioned medium (Wnt3a) overnight. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "C. Western blot analysis showing the effect of RNF43 cancer mutants on V5-FZD5 expression in HEK293T cells. Open and closed arrows indicate mature (post-Golgi) and immature (ER-associated) FZD5, respectively.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "D. Confocal microscopy of surface labeled SNAP-FZD5 in HEK293T cells upon expression of RNF43 WT or R519X. Cells were chased for 30 min. Scale bars represent 10 μm.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "E. Confocal microscopy of β-catenin localization in HEK293T cells expressing the indicated RNF43 cancer mutants. Scale bars represent 10 μm.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "F. Western blot analysis of RNF43 WT and R519X for cytoplasmic β-catenin levels.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "G. β-catenin-mediated reporter activity in HEK293T cells expressing Wnt3a and WT RNF43, oncogenic RNF43 (R519X) or a LOF RNF43 variant (I48T) after o/n treatment with DMSO or the PORCN inhibitor C59 (1 μM).",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "A. β-catenin-mediated reporter activity in HEK293T cells expressing WT RNF43 and oncogenic RNF43 (R519X) harboring mutations C290S/H292S in the RING domain (M1). Cells were treated with control medium (no Wnt3a) or Wnt3a-conditioned medium (Wnt3a) overnight. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "C. β-catenin-mediated reporter activity in HEK293T cells expressing the indicated RNF43 constructs. Cells were treated with control medium (no Wnt3a) or Wnt3a-conditioned medium (Wnt3a) overnight. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "D. β-catenin-mediated reporter activity in HEK293T cells co-expressing oncogenic RNF43 (R519X) and the Dishevelled DEP-C tail. Cells were treated with control medium (no Wnt3a) or Wnt3a-conditioned medium (Wnt3a) overnight. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "E. β-catenin-mediated reporter activity in HEK293T cells co-expressing oncogenic RNF43 (R519X) and dominant negative ∆N-TCF4. Cells were treated with control medium (no Wnt3a) or Wnt3a-conditioned medium (Wnt3a) overnight. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894
TCF4: 6925"
  },
  {
    "caption": "B. Western blot analysis of endogenous destruction complex components that co-precipitated with the indicated RNF43 cancer variants expressed in HEK293T cells. Oncogenic RNF43 truncations are indicated in red. Data information: IP; immunoprecipitation, IB; immunoblot",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "Confocal microscopy analysis of the subcellular localization of Axin1-GFP upon expression of WT or oncogenic RNF43 (R519X). Scale bars represent 10 μm. RNF43 is visualised by Flag-staining. Asterisks indicate RNF43-expressing cells.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "Confocal microscopy analysis of the subcellular localization of endogenous CK1α upon expression of WT or oncogenic RNF43 (R519X). Scale bars represent 10 μm. RNF43 is visualised by Flag-staining. Asterisks indicate RNF43-expressing cells.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "E. β-catenin-mediated reporter activity in HEK293T cells expressing non-mutated RNF43 R519X (SLSS) or the ALAA, DLDD and ∆486-89 mutants. Average β-catenin-mediated reporter activities ±s.d. in n = 2 independent wells are shown.",
    "ncbi_link": "RNF43: 54894"
  },
  {
    "caption": "A. Bright-field microscopy images of WT, TP53KO and onco-RNF43/TP53KO human colon organoid lines grown in medium with high Wnt/Rspo (20% conditioned medium (CM)) or without Wnt/Rspo (20, 2 or 0.2% CM). Images were taken 6 days after splitting. Scale bars represent 1000 μm. Non-cystic, non-proliferative organoids are indicated with red asterisks.",
    "ncbi_link": "RNF43: 54894
TP53: 7157"
  },
  {
    "caption": "C. Bright-field microscopy and fluorescence microscopy pictures of WT, TP53KO and onco-RNF43/TP53KO human colon organoid lines grown in two different media and transduced with the TOP-GFP reporter. Images were taken 6 days after splitting. Scale bars represent 1000 μm.",
    "ncbi_link": "GFP: 
RNF43: 54894
TP53: 7157"
  },
  {
    "caption": "D. Gene Set Enrichment Analysis of onco-RNF43/P53KO compared to TP53KO organoids in medium without Wnt/low Rspo (0.2%). Significantly changed intestinal cell-type gene sets from Haber et al., 2017() are shown (FDR < 0.05).",
    "ncbi_link": "RNF43: 54894
P53: 7157
TP53: 7157"
  },
  {
    "caption": "A. Top: Schematic experimental set up of the clonogenic assay. Bottom: Bright-field microscopy images of WT, TP53KO and onco-RNF43/TP53KO human colon organoid lines at day 2 and 14. Scale bars represent 1000 μm.",
    "ncbi_link": "RNF43: 54894
TP53: 7157"
  },
  {
    "caption": "B. Relative outgrowth of WT, TP53KO and onco-RNF43/TP53KO organoid lines treated with the PORCN inhibitor C59 (1 μM) for 7 days. Graph shows the number of organoids at 5 days after splitting (day 14) relative to the number of organoids at day 2. Error bars represent ±s.d. of the mean of n = 3 experiments.",
    "ncbi_link": "RNF43: 54894
TP53: 7157"
  },
  {
    "caption": "Kaplan-Meier survival curves stratified by the patient MICA-129 genotype for all patients (n = 446). The survival curve is displayed for the first 66 months; 7.6% of the patients were followed longer. Effects on overall survival were determined by Cox regression with covariate adjustment as indicated in Table2. The HR indicates the risk per MICA-129Met allele carried by the patients (additive risk model). The numbers of patients carrying the three genotypes and the number of events (in brackets) are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "Kaplan-Meier survival curves for patients receiving a graft matched for the MICA-129 genotype (n = 404).",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "Kaplan-Meier survival curves for patients not experiencing aGVHD (n = 189). The HR indicates the risk of patients carrying two MICA-129Met alleles (recessive risk model).",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "Kaplan-Meier survival curves for patients with the MICA-129Val/Val genotype (n = 229) stratified by treatment with ATG.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "Kaplan-Meier survival curves for patients carrying one or two MICA-129Met alleles (n = 214) stratified by treatment with ATG.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "The linear regression of MICA expression intensity and binding of a recombinant NKG2D-Fc fusion protein both determined as MFI by flow cytometry is displayed for L-MICA-129Met (n = 79, left panel) and L-MICA-129Val clones (n = 81, right panel). The coefficients of determination (R2), the regression coefficients (reg. coeff.), and the P-values for Pearson correlation are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "The degranulation of IL-2-stimulated LAK cells (100 U/ml for 4 days) exposed to L-MICA-129Met (n = 27) or L-MICA-129Val clones (n = 27) for 1 h was determined by flow cytometry. CD107a cell surface expression was analyzed after gating on CD56+ NK cells. In parallel, the MICA expression on target cells was determined. Displayed are the linear regressions of the MFI of CD107a on NK cells (upper panels) or the proportion of CD107a+ NK cells (lower panels) and the MICA expression intensity on target cells (MFI) for the L-MICA-129Met (left panels) and L-MICA-129Val clones (right panels). The coefficients of determination (R2), the regression coefficients (reg. coeff.), and the P-values for Pearson correlation are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "A representative of 21 experiments is shown demonstrating the specific cytotoxic activity of LAK cells against an L-MICA-129Met and an L-MICA-129Val clone. L-con cells served as a negative and K562 cells as a positive control. The means of specific lysis of triplicates plus SD at different E:T ratios (200:1 to 3:1) were measured in an 51chromium-release assay. The MICA expression intensity and the binding of a recombinant NKG2D-Fc fusion protein to the target cells were determined in parallel by flow cytometry, and the MFIs are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "The IFNγ expression of purified IL-2-stimulated (100 U/ml for 4 days) NK cells exposed for 4 h to L-MICA-129Met (n = 23) or L-MICA-129Val clones (n = 23) was determined by flow cytometry. The IFNγ expression was analyzed after gating on CD56brightCD16−NK cells. In parallel, the MICA expression on target cells was determined. Displayed are the linear regressions of the MFI of IFNγ in CD56brightCD16−NK cells (upper panels) or the proportion of IFNγ+CD56brightCD16−NK cells (lower panels) and the MICA expression intensity on target cells (MFI) for the L-MICA-129Met (left panels) and L-MICA-129Val clones (right panels). The coefficients of determination (R2), the regression coefficients (reg. coeff.), and the P-values for Pearson correlation are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "The IFNγ release of purified IL-2-stimulated NK cells (100 U/ml for 4 days) co-cultured with L-MICA-129Met (n = 34) or L-MICA-129Val clones (n = 32) for 24 h was measured in the supernatant by ELISA. In parallel, the MICA expression intensity on target cells was determined by flow cytometry. The linear regressions of IFNγ release (pg/ml) by NK cells and MICA expression on targets (MFI) are displayed for the L-MICA-129Met clones (left panel) and the L-MICA-129Val clones (right panel). The coefficients of determination (R2), the regression coefficients (reg. coeff.), and the P-values for Pearson correlation are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "NKG2D expression on purified IL-2-stimulated NK cells (100 U/ml for 4 days) exposed to L-MICA-129Met (n = 25) or L-MICA-129Val clones (n = 25) for 0, 4, and 24 h was analyzed by flow cytometry. NK cells (2.5 × 105) were co-cultured with 5 × 104 target cells and analyzed for NKG2D expression after gating of CD3−CD56+ cells. The means and SD of the percentage of NKG2D+ NK cells (left panel) and of the MFI of NKG2D (right panel) are shown. Differences between the groups were analyzed by repeated measures ANOVA, and P-values for pairwise comparisons are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "NKG2D expression on purified CD8+T cells exposed to L-MICA-129Met (n = 19) or L-MICA-129Val clones (n = 19) for 0, 4, and 24 h was analyzed by flow cytometry. CD8+T cells (2.5 × 105) were co-cultured with 5 × 104 target cells and analyzed for NKG2D expression after gating on CD3+CD8+T cells. The means and SD of the MFI of NKG2D (left panel) and of the percentage of NKG2D+CD8+T cells (right panel) are displayed. Differences between the groups were analyzed by repeated measures ANOVA, and the P-values are indicated.",
    "ncbi_link": "MICA: 100507436"
  },
  {
    "caption": "A Heart rate (HR) of WT and Adcy9-/- mice averaged over 5 min of non-active versus sustained activity on home cage running wheels. Student's t-test P values for indicated comparisons are shown. Circles represent data from individual animals. The boxplot central band is the median while whiskers represent the 10th and 90th percentiles.",
    "ncbi_link": "Adcy9: 11515"
  },
  {
    "caption": "B,C HR and R-R interval of WT (black bars) and Adcy9-/- mice (red bars) before and after ISO (1 μg/g) injection",
    "ncbi_link": "Adcy9: 11515"
  },
  {
    "caption": "D Representative ECG recordings of 7 mo WT and Adcy9-/- mice, ~55 min post ISO-injection.",
    "ncbi_link": "Adcy9: 11515"
  },
  {
    "caption": "A,B PLA assay performed in neonatal cardiomyocytes expressing GFP-Flag or AC9-Flag using antibodies against Flag and endogenous POPDC1, POPDC2 or Gβγ. Images (A); scale bar is 20 um; nuclear staining by DAPI shown in blue) and quantitation (B) of PLA signal are shown.",
    "ncbi_link": "Flag: 
GFP: 
AC9: 115"
  },
  {
    "caption": "A HEK293 cells expressing Flag-AC9 in the presence or absence of Myc-tagged POPDC1 or -2 were subjected to co-immunoprecipitation (Co-IP) with anti-MYC and assayed for AC activity with 300 nM Gαs-GTPγS. Kruskal-Wallis One Way ANOVA analysis on Ranks was performed (n=6 experiments, P=0.003 between all groups) with multiple comparisons to AC9 control by Dunn's method and Mann-Whitney Rank Sum Test (**P=0.002).",
    "ncbi_link": "Myc: 
AC9: 115
POPDC1: 23828"
  },
  {
    "caption": "B A portion of the lysates and Co-IP from (A) were subjected to western blot (WB) analysis. Sf9 cells expressing Flag-AC9 served as a positive WB control. Molecular weight markers are denoted as M. Quantitation of Flag-AC9 WB by One Way ANOVA, n=3-4 experiments, with comparisons by Tukey test, **P=0.003, ***P=0.001.",
    "ncbi_link": "Flag: 
AC9: 115"
  },
  {
    "caption": "(C) HEK293 cells expressing Flag-AC9 +/- POPDC1-Myc or POPDC2-Myc were subjected to Co-IP with anti-FLAG and subjected to WB analysis with anti-MYC and anti-FLAG. Quantitation of anti-MYC WB by One Way ANOVA, n=4 experiments, with comparisons by Tukey test, **P=0.003, ***P<0.001).",
    "ncbi_link": "Flag: 
Myc: 
AC9: 115
POPDC1: 23828
POPDC2: 64082"
  },
  {
    "caption": "(D) HEK293 cells expressing POPDC1-Myc +/- GFP-tagged AC9 and control TM proteins EGFR, or LAMP1 were subjected to Co-IP with anti-MYC. Western blotting of lysates and Co-IPs for GFP (top) and MYC (bottom) are shown (n=3 experiments).",
    "ncbi_link": "GFP: 
Myc: 
AC9: 115
POPDC1: 23828"
  },
  {
    "caption": "(F) BiFC of AC9 and indicated POPDC1 truncations in COS-7 cells. Kruskal-Wallis One Way ANOVA analysis was performed (n=4 experiments) with multiple comparisons by Tukey test, ***P<0.001 compared to VN control, **P=0.008.",
    "ncbi_link": "POPDC1: 23828"
  },
  {
    "caption": "(G) Co-IP with anti-MYC in COS-7 cells expressing Flag-AC9 and indicated Myc-tagged POPDC1 truncations. Western blotting with anti-AC9 and anti-MYC (POPDC1) of Co-IP and lysates is shown. Kruskal-Wallis One Way ANOVA analysis was performed (n=3-5 experiments, P=0.006), with multiple comparisons by Dunn's method (*P=0.021, **P=0.01).",
    "ncbi_link": "Flag: 
Myc: 
AC9: 115
POPDC1: 23828"
  },
  {
    "caption": "A IP-AC assay with IgG versus anti-TREK-1 in heart homogenates from WT and Adcy9-/- mice; AC activity stimulated with 300 nM Gαs-GTPγS. IP-AC with anti-AKAP150 is shown as a positive control. Two-way ANOVA (overall P<0.001, n=3 mice per genotype) with multiple comparisons by Holm-Sidak test; #P<0.001 for indicated comparison or to respective IgG controls. IgG versus anti-TREK-1 in Adcy9-/- was analyzed by Student's t-test (**P=0.009, n=3). A portion of the co-IP was subjected to western blotting with anti-TREK-1 and anti-AKAP150.",
    "ncbi_link": "Adcy9: 11515"
  },
  {
    "caption": "B IP-AC assay with IgG versus anti-TREK in WT and Popdc1-/- mouse heart homogenates; AC activity stimulated as in (A). Statistics as in (A), n=4 mice per genotype, #P<0.001. Paired t-test within Popdc1-/-, P=0.123.",
    "ncbi_link": "Popdc1: 23828"
  },
  {
    "caption": "C Total AC activity in heart homogenates from WT or Popdc1-/- (P1-/-) mice stimulated with 300 nM Gαs-GTPγS or 100 μM calcium and 300 nM calmodulin.",
    "ncbi_link": "P1: 23828
Popdc1: 23828"
  },
  {
    "caption": "D IP-AC assay with anti-MYC from cell lysates expressing AC1 or AC8 in the presence or absence of Myc-tagged POPDC1. AC activity stimulated with 100 μM calcium and 300 nM calmodulin. Student's t-test (n=3 experiments, **P=0.0011 and *P=0.012).",
    "ncbi_link": "Myc: 
POPDC1: 23828"
  },
  {
    "caption": "E IP-AC assay with IgG versus anti-TREK-1 in WT and Popdc1-/- mouse heart homogenates; AC activity stimulated as in (D). Student's t-test (*P=0.03; **P=0.005, n=4 mice per genotype).",
    "ncbi_link": "Popdc1: 23828"
  },
  {
    "caption": "D TREK-1:AC9 BiFC signal is absent in COS-7 cells lacking detectable POPDC1. TREK-1:TREK-1 BiFC is a positive control. One-way ANOVA with multiple comparisons by Holm Sidak method (n=3 experiments; ***P<0.001).",
    "ncbi_link": "POPDC1: "
  },
  {
    "caption": "E Overexpression of POPDC1 truncation of Popeye domain (POPDC1-Δ172), but not WT POPDC1, abolishes ISO reduction of TREK-1:AC9 BiFC signal. One-way ANOVA with multiple comparisons by Holm Sidak method (n=3-4 experiments; ***P<0.001 compared to control).",
    "ncbi_link": "POPDC1: 
POPDC1: 23828"
  },
  {
    "caption": "A Representative two-electrode voltage clamp measurements in Xenopus oocytes injected with TREK-1 alone (orange) or TREK-1 co-injected with cRNAs encoding the indicated proteins. Voltage was ramped from -120 to +40 mV. B Relative TREK-1 current amplitudes at +40 mV normalized to TREK-1 injected alone. The number of oocytes is given within the bar graphs (n=37-97). 3-5 batches of oocytes were used for each condition.",
    "ncbi_link": "TREK-1: 3776"
  },
  {
    "caption": "Approximately 500 bp of genomic sequence, with and without Alu  inserts was assayed for transcription activity when inserted upstream of a minimal promoter in a luciferase  vector transfected into NCRM1  cells. The orientation (white triangle) of the Alu  and its associated genomic sequence (yellow box) is diagramed at top. Forward orientation (Fwd) indicates plus strand sequence of the reference genome. The minimal promoter is symbolized by a black rectangle with an arrow indicating the direction of transcription. The causal TE candidates tested, their linked TASs, and their ChromHMM status are indicated at right. Luciferase values are normalized to transfection efficiency (renilla) for each of four independent transfections and subsequently to luciferase  expression from the minimal promoter alone. Mean values (± SD) were determined, and statistical significance was analyzed by Student's two-sample unequal variance t-Test with a one-tailed distribution. Each locus was examined in four independent experiments and a representative dataset is shown here. ☨: p < 0.05 in two experiments and p > 0.05 in two experiments. ns: P > 0.05.",
    "ncbi_link": "Luciferase: 
luciferase: "
  },
  {
    "caption": "A-C Confocal images of primary hepatocytes grown under indicated conditions and stained with anti-CLUH antibody and Hadha (A), Pcx (B) and Actb (C) mRNA in situ hybridization. Right panels show 5x magnified boxed areas. Scale bar, 10 μm. D-F Manders' colocalization coefficient between Hadha (D) Pcx (E) and Actb (F) mRNA molecules and CLUH signal (n ≥ 50 cells isolated from 3-6 mice). Data information: In (D-F), data are presented as boxplots showing the median, the first and the third quartile. Error bars show minimum and maximum values. ***, P≤0.001 (Student's t-test).",
    "ncbi_link": "Actb: 11461
Hadha: 97212
Pcx: 18563"
  },
  {
    "caption": "A-C Confocal images of primary hepatocytes after ribopuromycylation experiment combined with mRNA in situ hybridization for (A) Hadha, (B) Pcx and (C) Hmgcs2. Scale bar, 4 µm. D-F Fluorescence profile of 100-pixel line from the merged channel shown in (A-C). The cells from which the enlarged areas (400 μm2) have been magnified are shown in Appendix Figure S2 for each individual channel. Cells analyzed were isolated from 6 different mice with similar results. ",
    "ncbi_link": "Hadha: 97212
Hmgcs2: 15360
Pcx: 18563"
  },
  {
    "caption": "A Representative western blot of HeLa cells downregulated for G3BPs and overexpressing untagged CLUH. Asterisks indicates signal of previous incubation with anti-G3BP1 antibody. Pan-actin was used as loading control.",
    "ncbi_link": "CLUH: 23277
G3BPs: 9908///10146"
  },
  {
    "caption": "B Confocal images of anti-CLUH staining in HeLa cells downregulated for G3BPs and overexpressing untagged CLUH. Insets show 2.6x enlarged area. Scale bar, 10 µm. C Quantification of cells with CLUH-granules from experiments shown in (B) (n=3 independent experiments, >50 cells per experiment per condition). Data information data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test). ",
    "ncbi_link": "CLUH: 23277
G3BPs: 10146///9908"
  },
  {
    "caption": "D Life imaging of WT and CLUH KO HeLa cells transfected with G3BP1-GFP plasmid and incubated in HBSS medium with or without CHX. Cells were recorded for a maximum of 2 h. Insets show 2.5x enlarged areas. Scale bar, 10 µm. E Total number of cells analyzed by life imaging for the indicated experiments shown in (D). \"Positive\" relates to a cell which formed G3BP1 granules at the end of the recording. ",
    "ncbi_link": "GFP: 
CLUH: 23277
G3BP1: 10146"
  },
  {
    "caption": "F Confocal images of anti-G3BP1 staining in primary hepatocytes derived from Li-CluhWT and Li-CluhKO mice grown in indicated media. Arrows point to G3BP1-granules. Scale bar, 10 µm. G Quantification of percentage of cells with G3BP1-positive granules of experiment shown in F. Cells were analyzed in a blind fashion (n=3 mice per genotype; number of cells in total: WT Basal, 449; KO Basal, 303; WT HBSS, 146; KO HBSS, 161). Data information: , data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test). ",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "J mRNA levels of G3bp1 in primary hepatocytes grown under indicated conditions. (n=4 per genotype per condition). Data information data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test). ",
    "ncbi_link": "G3bp1: 27041"
  },
  {
    "caption": "F Correlation of protein fold changes in KO in respect to WT hepatocytes under basal condition and upon HBSS (2 h). Only genes previously found in CLUH RIP experiments in HeLa cells (Gao et al., 2014) are plotted. Inset shows magnification of upper part of the graph.",
    "ncbi_link": "CLUH: 23277"
  },
  {
    "caption": "D Representative western blot of total protein extracts from livers of starved Li-CluhWT and Li-CluhKO mice probed with indicated antibodies. GAPDH was used as loading control. E, F Quantification of western blots as shown in (D). Antibody signal was normalized to GAPDH signal and signal of phospho-protein was normalized to signal of the total protein (n=8 mice per genotype). Data information: data are presented as histograms showing the mean ± SEM. Error bars show minimum and maximum values. ***, P≤0.001 (Student's t-test). (H, J) *, P≤0.05; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test).",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "I IHC staining of cleaved caspase 3 in liver sections of starved Li-CluhWT and Li-CluhKO mice. Arrows point to positive apoptotic foci. Scale bar, 200 µm.",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "A Confocal images of liver cryosections from Li-CluhWT and Li-CluhKO-LC3-GFP mice. Scale bar, 25 µm. B Quantification of LC3 signal morphology of images shown in (A). Graphs show relative number of LC3 autophagosomes and the relative area occupied per nuclei. 4 images were quantified per animal and averaged. Nuclear staining was excluded for the analysis (n=4 mice per genotype). Data information: data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (Student's t-test).",
    "ncbi_link": "GFP: 
Cluh: 74148
LC3: 64862///362245"
  },
  {
    "caption": "C Confocal images of primary hepatocytes derived from Li-CluhWT and Li-CluhKO-LC3-GFP mice. Hepatocytes were starved for 2 h in HBSS. Scale bar, 10μm. D-E Quantification of LC3 puncta number (D) and area (E) per cell (n ≥100 cells isolated from 3 mice). Data information: In (D, E), data are presented as boxplots showing the median, the first and the third quartile. Error bars show minimum and maximum values. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test).",
    "ncbi_link": "GFP: 
Cluh: 74148
LC3: 362245///64862"
  },
  {
    "caption": "F Western blot of total protein extracts from livers of Li-CluhWT and Li-CluhKO mice probed with LAMP1. GAPDH was used as loading control. G Quantification of western blot shown in (F). WT: n=4; KO: n=3. Data information: In data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (Student's t-test).",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "Western blot analysis of total protein extracts from livers of 8 weeks old Li-CluhWT and Li-CluhKO mice probed with indicated antibodies. GAPDH was used as loading control. B Quantification of western blot shown in (A). WT: n=4; KO: n=3. Data information data are presented as histograms showing the mean ± SEM. ***, P≤0.001; *, P≤0.05 (Student's t-test).",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "C Western blot analysis of isolated mitochondria from Li-CluhWT and Li-CluhKO mice probed with indicated antibodies. PonceauS staining was used as a loading control.",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "E Confocal images of liver cryosections derived from Li-CluhWT and Li-CluhKO-LC3-GFP mice and stained with anti-TOM20 antibody. On the right side, indicated boxes were 3.5x magnified. Arrows point to colocalizing spots. Scale bar, 25 μm. F Manders' colocalization coefficient between TOM20 and LC3 from experiments shown in (E). 5 images were analyzed per animal to get an averaged value (n=5 mice per genotype). Data information , data are presented as histograms showing the mean ± SEM. ***, P≤0.001; *, P≤0.05 (Student's t-test).",
    "ncbi_link": "GFP: 
Cluh: 74148
LC3: 64862///362245"
  },
  {
    "caption": "G Confocal images of primary hepatocytes derived from Li-CluhWT and Li-CluhKO-LC3-GFP mice and stained with anti-TOM20 antibody. When indicated cells were treated with rapamycin (200 nM for 4h). Bottom panels show 2.3x magnified areas for each channel of indicated boxes. Arrows point to colocalizing spots. Scale bar, 10 μm. H Manders´ colocalization coefficient from experiment shown in (G) (n ≥ 50 cells isolated from 3 mice per genotype). Data information: In (H), data are presented as boxplots showing the median, the first and the third quartile. Error bars show minimum and maximum values. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test).",
    "ncbi_link": "GFP: 
Cluh: 74148
LC3: 362245///64862"
  },
  {
    "caption": "I Confocal images of WT and Cluh KO MEFs transfected with mCherry-GFP-FIS101-152 and grown for 16 h in galactose medium or in medium containing 10 μM antimycin A/ oligomycin. Arrows indicate mitophagosomes. Scale bar, 10μm. J Quantification of percentage of cells with mitophagosomes. Cells were considered positive when red signal was clearly recognizable (n= 3-5 independent experiments, >100 cells per experiment). Data information: data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test).",
    "ncbi_link": "GFP: 
mCherry: 
Cluh: 74148"
  },
  {
    "caption": "K Confocal images of WT and Cluh KO MEFs transfected with mCherry-GFP-FIS101-152, incubated with 200 nM rapamycin and grown for 16 h in galactose medium or in medium containing 10 μM antimycin A/ oligomycin. Arrows indicate mitophagosomes. Scale bar, 10 μm. L Quantification of percentage of cells with mitophagosomes. Cells were considered positive when red signal was clearly recognizable (n= 3-5 independent experiments, >100 cells per experiment). Data information: data are presented as histograms showing the mean ± SEM. *, P≤0.05; **, P≤0.01; ***, P≤0.001 (One-way ANOVA, Tukey's multiple comparisons test).",
    "ncbi_link": "GFP: 
mCherry: 
Cluh: 74148"
  },
  {
    "caption": "A Confocal images of liver cryosections from Li-CluhWT and Li-CluhKO mice injected with rapamycin or mock solution and stained with anti-TOM20 antibody. Scale bar, 25 µm. B Quantification of morphological parameters of experiments shown in (A). 4 images were quantified per animal and averaged. Nuclear staining was excluded for the analysis (n=3 mice per genotype).Data information: data are presented as histograms showing the mean ± SEM. **, P≤0.01; *, P≤0.05 (Student's t-test).",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "C Confocal images of liver cryosections from Li-CluhWT and Li-CluhKO mice injected with rapamycin or mock solution and stained with anti-LAMP1 antibody. Scale bar, 25 µm. D Quantification of morphological parameters of experiments shown in (C). 4 images were quantified per animal and averaged. Nuclear staining was excluded for the analysis (n=3 mice per genotype). Data information: , data are presented as histograms showing the mean ± SEM. **, P≤0.01; *, P≤0.05 (Student's t-test).",
    "ncbi_link": "Cluh: 74148"
  },
  {
    "caption": "(A) Proof-of-principle experiment. Time-lapse images show overexpression of Myc-tagged CPAP-WT (i) or CPAPΔT (ii) has no effect on two centrosome-containing MCF10A cells (-Dox, two centrosomes). The cells were imaged from interphase to Cytokinesis. Bar graph at right quantifies mitotic duration of cells overexpressing CPAP-WT and CPAPΔT. We define mitotic duration as time consumed from the onset of cell rounding until cytokinesis. Number of cells (n) analyzed in each condition is indicated at the top of each bar. Number of independent experiments (N), (N)=3. Error bars, mean ± SEM. Unpaired t-test. CPAP-WT (iii) or CPAPΔT (iv) expressing extra centrosome-containing MCF10A cells (+Dox, extra centrosomes). Note compared to CPAP-WT expressing centrosomes (iii) CPAPΔT expressing centrosomes nucleate enhanced levels of microtubule asters already at prophase-like stage (iv). White arrows indicate centrosomal dots. Red arrows indicate centrosomes nucleating microtubule asters causing multipolar spindles. Scale bar, 2µm. Bar graph at right quantifies mitotic duration and percentage of cells exhibiting prolonged mitosis in cells expressing CPAP-WT and CPAPΔT. (N)=3. Error bars, mean ± SEM. Unpaired t-test ***P < 0.0001",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(B-D) Fixed cell images showing the expression of CPAP-WT (top panel) and CPAPΔT (bottom panel) in extra centrosome containing MCF10A (+Dox, extra centrosomes), MDA-MB-231 and H1975T790M cells. Note, in CPAP-WT expressing cells, clustered extra centrosomes remain inactive with no or reduced microtubule nucleation. On the other hand, CPAPΔT expression enhances microtubule nucleation in extra centrosomes (arrows) and preventing them from clustering at G2-like interphase and mitosis. Cells were stained with CPAP (GFP), microtubules (α-tubulin, red), Cep152 (magenta). Scale bar, 2µm",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(E) Bar graph quantifies percentages of mitotic cells exhibiting multipolar spindles upon CPAP-WT or CPAPΔT expression. (N)=3. Error bars, mean ± SEM. Unpaired t-test **P < 0.001",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(F) Subcutaneous xenograft tumor volume measurements of MDA-MB-231 cells expressing CPAP-WT (red) as control or CPAPΔT (blue) in nude mice. (i) Bar graph at right shows total tumor volume reduction at day 22. (ii) Each condition used 4 mice each containing 4 xenograft tumors. Error bars, mean ± SEM with n = 16 for CPAP-WT and n = 16 for CPAPΔT. Unpaired t-test ***P < 0.0001.",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(i) Experimental strategy to test if the effect of CCB02 is CPAP dependent in MCF10A cells containing extra centrosomes (+Dox, extra centrosomes) (A Cells were treated with CPAP siRNA and control (scramble) siRNA for 48 hours. (ii) Western blots show depletion of CPAP when cells were treated with siRNA specific for CPAP",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "Experimental strategy to test if the effect of CCB02 is CPAP dependent i MDA-MB-23 cell (B). Cells were treated with CPAP siRNA and control (scramble) siRNA for 48 hours. (ii) Western blots show depletion of CPAP when cells were treated with siRNA specific for CPAP",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(C) Fractions of cells containing centrosomes after siRNA treatment. 48 hours of siRNA treatment still contained a fraction of cells with extra centrosomes that were analyzed in the following experiments. Bar graph shows the percentage of cells with extra centrosomes in MCF10A (+Dox, extra centrosomes) in the presence of control siRNA or CPAP siRNA. Data represent mean ± SEM of three independent experiments. (N)=3, (n=300 cells per condition). p values were obtained using Ordinary One-way ANOVA test *P < 0.01, **P < 0.001",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(D) Effect of CCB02 in the presence of control siRNA and CPAP siRNA in MCF10A (i) MDA-MB-231 cells (ii) CPAP depletion does not prevent centrosomes from clustering (second rows of i and ii). Note, in CPAP depleted cultures, centrosomes are marked with Cep152 (green) where CPAP (magenta) is detected faintly. In CPAP depleted cells, CCB02 does not prevent extra centrosomes from clustering (fourth rows of i and ii). Note CCB02 does prevent extra centrosomes from clustering in cultures treated with control siRNA (third rows of i and ii). Cells are stained for Cep152 (green), CPAP (magenta), microtubules (α-tubulin, red) and DNA (DAPI, blue). Scale bar, 2µm",
    "ncbi_link": "CPAP: 55835"
  },
  {
    "caption": "(F) Freeze-substitution fixation image of a Cvt complex in strain SEY6210 transformed with a 2μ plasmid encoding API grown in SD medium.",
    "ncbi_link": "API: 853758"
  },
  {
    "caption": "(G) Immunostaining of strain SEY6210 containing a 2μ APE1 plasmid grown in SD medium. N, Nucleus; V, vacuole.",
    "ncbi_link": "APE1: 853758"
  },
  {
    "caption": "Transport of Cvt complex in SEY6210 (wild-type) harboring 2μ plasmid encoding API under growing and nitrogen starvation conditions. Vegetative cells grown in SD medium were observed (A-E). For starvation, logarithmically growing cells in SD were transferred to SD(-N) for 25 min (F-H) or 1 h (I-K) in the presence of 1 mM PMSF. Samples were prepared for electron microscopy as described in Fig. 1. (A) Freeze-substitution fixation image of Cvt vesicle (marked with an arrow). (B) Immunostaining of a Cvt vesicle (marked with an arrow). (C and D) Higher magnification image of Cvt vesicle. Arrowhead and double arrowheads show the inner and outer membrane of a Cvt vesicle, respectively. (E) Freeze-substitution fixation image of a membrane sac enclosing small portion of a large Cvt complex (marked with an arrow). (F) Freeze-substitution image of the wrapping of a Cvt complex by the isolation membrane (marked with an arrow). (G) Freeze-substitution image of a Cvt vesicle (marked with an arrow) fusing to a vacuole. (H) Freeze-substitution image of autophagic body containing a Cvt complex. (I) Immunostaining image depicting the wrapping of a Cvt complex. The arrow marks the enwrapping membrane. (J) Immunostaining of an autophagosome containing a Cvt complex. (K) Immunostaining of an autophagic body containing a Cvt complex in the vacuole. V, vacuole.",
    "ncbi_link": "API: 853758"
  },
  {
    "caption": "Mutant analysis allows for differentiation between vacuolar delivery by Cvt vesicles and autophagosomes. (A) SEY6210 (wild-type), cvt3, and cvt7 yeast were grown in SD to 1 OD600 U/ml and transferred to SD (-N). Aliquots were collected after 0 h (+) and 4 h (−) incubation and subjected to immunoblotting. The positions of precursor (pro) and mature (m) API are indicated. (B) cvt3 and cvt7 cells were pulse labeled for 10 min. After addition of cold cysteine and methionine, the cells were harvested, washed, and resuspended in either SD or SD(-N) and chased for the indicated times. API was recovered by immunoprecipitation, resolved on SDS polyacrylamide gels, and quantified using a phosphorimager (STORM; Molecular Dynamics, Sunnyvale, CA).",
    "ncbi_link": "cvt3: 856162
cvt7: 851406"
  },
  {
    "caption": "Analysis of the Cvt complex in the cvt3 mutant under vegetative and starvation conditions. Vegetative cells were grown in SD medium at 30°C to log phase. For starvation, logarithmically growing cells in SD medium were transferred to SD(-N) for 5 h. Samples were prepared for electron microscopy as described in Fig. 1. (A) Immunostaining image depicting Cvt complex in the cytosol. Cvt vesicles are not detected in this strain. (B) Freeze-substitution fixation image showing Cvt complex in autophagosome (marked with an arrow) under starvation conditions, indicating that autophagy can still proceed. AP, Autophagosome; N, nucleus; V, vacuole.",
    "ncbi_link": "cvt3: 856162"
  },
  {
    "caption": "Mice received daily intraperitoneal (IP) injections of A151 (300 μg) or an equal volume of vehicle for 3 consecutive days after MCAO induction. (A) The mRNA expression levels of the cGAS and STING after MCAO were determined using qRT-PCR. n = 6 mice per group. **",
    "ncbi_link": "cGAS: 214763
STING: 72512"
  },
  {
    "caption": "(D) The mRNA expression levels of the AIM2 inflammasome components (AIM2, ASC, and caspase-1), effector of pyroptosis GSDMD, IL-1β, and IL-18 after MCAO were determined using qRT-PCR. n = 6 mice per group.",
    "ncbi_link": "AIM2: 383619
caspase-1: 12362
GSDMD: 69146
IL-18: 16173
IL-1β: 16176
ASC: 66824"
  },
  {
    "caption": "(D) Representative genotyping analysis for WT, cGAS-KD, and cGAS-KO mice.",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "(F) Representative images of TTC staining of brain sections from vehicle-treated WT MCAO mice, vehicle-treated cGAS-KO mice, and A151-treated cGAS-KO mice on day 3 after tMCAO. Three representative rostrocaudal levels of TTC staining are shown. (G) Bar graph shows percentages of infarct volume of indicated group. n = 6 mice per group. (H) Bar graph shows modified Neurological Severity Score (mNSS) in vehicle-treated WT MCAO mice, vehicle-treated cGAS-KO mice, and A151-treated cGAS-KO mice n = 10 mice per group.",
    "ncbi_link": "cGAS: 214763"
  },
  {
    "caption": "A, B 1 × 105 B16F10 melanoma cells were intravenously injected into C57BL/6 wild-type (WT) or Asm-deficient (Asm−/−) mice, and the number of lung metastases was determined after 14 days. The photographs (A) show two representative results. The graph (B) shows the mean ± SD number of pulmonary metastases in 15 WT and 14 Asm-deficient animals.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "C, D B16F10 melanoma grow as fast or slightly faster in Asm-deficient mice than in wild-type mice after subcutaneous injection at the flank (C) or transcutaneous direct intrapulmonary injection (D), excluding a general growth defect of the tumor in Asm-deficient mice. The size of tumors was determined 14 days after local injection at the flank or 10 days after injection into the lung.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "F 5 × 108platelets isolated from wild-type (WT) or Asm-deficient (Asm−/−) mice were injected intravenously into Asm-deficient or wild-type mice, respectively. After 120 min 1 × 105, B16F10tumor cells were intravenously injected. The number of lungmetastases was determined after 14 days. Displayed are the mean ± SD of the number of pulmonary metastases, n = 3 in WT platelets in WT mice, n = 5 in WT platelets in Asm−/−mice, and n = 4 in Asm−/−platelets in Asm−/−mice.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "A Platelets were isolated from wild-type (WT) or Asm-deficient (Asm−/−) mice by density-gradient centrifugation, and 1 × 107 platelets were incubated with 1 × 105 B16F10 cells. The samples were lysed, and Asm activity was determined. In unstimulated samples (time point of co-incubation 0 s), tumor cells and platelets were admixed after lysis.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "C, D For determination of the secretion of Asm by platelets into the supernatants (C), tumor cells and wild-type (WT) or Asm-deficient (Asm−/−) platelets were co-incubated for 20 s, the samples were pelleted, the supernatants were removed and acidified, and the Asm activity was measured in the presence or absence of Zn2+. For measurement of surface Asm and ceramide, samples were co-incubated as indicated (C, D) and pelleted; the supernatants were discarded, incubated with anti-Asm antibodies, washed, and lysed; and Asm immunocomplexes were immobilized and subjected to immunocomplex enzyme assays. Surface ceramide was measured by incubation of intact cells with DAG kinase in the presence of [32P]γATP followed by extraction and measurement of [32P]-ceramide. Omission of one cell type indicated by \"−\" here and thereafter.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "E Treatment of B16F10tumor cells for 2 min with 1 U/ml ASM or 10 μM C16ceramide restores in vivo metastasis in Asm-deficient mice. After treatment, the cells were injected intravenously into Asm-deficient (Asm−/−) mice. Controls were left untreated prior to injection. The number of metastases was determined 14 days after tumor cell injection.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "Suppression of Asm in B16F10 tumor cells using siRNA technology reduces Asm activity in B16F10 cells (right panel), but does not alter release or surface activity of the Asm after co-incubation with wild-type platelets (left panels).",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "Platelets were isolated from wild-type (WT) or Asm-deficient (Asm−/−) mice by density-gradient centrifugation, and 1 × 107platelets were incubated with 1 × 105B16F10 cells or left untreated. Co-incubation of washed platelets with B16F10 melanoma cells resulted in upregulation of GPIIb/IIIa and CD62P on both wild-type and Asm-deficient platelets in FACS analyses. Platelets were gated in FCS/SSC.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "Aggregation properties of platelets after co-incubation with collagen or ADP are independent of Asm as determined by aggregometry measurements.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "4 × 104B16F10tumor cells were incubated with 2 × 107 wild-type (WT), Asm-deficient (Asm−/−) platelets (Plts) or a 45:55 of WT:Asm−/−platelet mixture in the presence or absence of 50 ng/ml PGE1. Controls were stimulated with Mn2+. Tumor cells were then incubated for 60 s on fibronectin-coated cover slips, washed, and fixed, and adhesion of the tumor cells was determined. The graph displays the mean ± SD of tumor cells adhering to fibronectin-coated cover slips, n = 7 for WT-platelets, n = 9 for Asm-deficient-platelets, n = 4 for 45:55 WT:Asm−/−platelets, and all others n = 3. Statistical significance was determined by analysis of variance (ANOVA) followed by Tukey's multiple comparisons test. P-values are indicated.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "A-C 1 × 105 B16F10 cells were incubated with (A) 1 U/ml purified acid sphingomyelinase (ASM) or (B) 5 × 107 wild-type (WT), Asm-deficient (Asm−/−) platelets (Plts), or a mixture of 45:55 wild-type:Asm-deficient platelets. Cells were fixed with 2% paraformaldehyde for 15 min and stained with fluorescein isothiocyanate (FITC)-coupled anti-α5 integrin, Cy3-labeled anti-β1 integrin, and Cy5-labeled anti-ceramide antibodies. Samples were analyzed by confocal microscopy. Shown are representative examples from four independent experiments (A, B) or the quantitative analysis of cells positive for ceramide/β1 integrin clusters from at least 100 cells/sample (C). Given is the mean ± SD, n = 4, ANOVA followed by Tukey's multiple comparisons test. P-values are indicated.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "E Intravenous injection of CFSE-labeled B16F10 cells into wild-type mice results in formation of ceramide-enriched domains that contain β1 integrin clusters on tumor cells in vivo, while injection of tumor cells into Asm-deficient mice does not result in ceramide and integrin clustering. Please note that the cell in the lower panel still binds a platelet. Shown are representative results from four independent experiments each.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "B16F10tumor cells or B16F10 transfected with siRNA targeting Asm expression or with scrambled control siRNA were labeled with [3H]thymidine, washed, and treated (+) for 10 min with 1 U/ml ASM, 10 μM C16ceramide, 10 μM S1P, 10 μM PDMP, 20 μM sphingosine kinase inhibitor SKI II, and 10 μM myriocin, or left untreated (−). The cells were then injected intravenously into wild-type or Asm-deficient mice as indicated. If indicated, 10 μg of arginine-glycine-aspartic acid (RGD) peptide or 10 μg/ml neutralizing anti-β1 integrin antibodies were added to B16F10tumor cells together with ASM for 15 min prior injection. Mice were sacrificed 30 min after tumorcell injection, the lungs carefully flushed via the right heart, and the radioactivity in the lung as a measurement for adherent tumor cells was determined. Shown is the mean ± SD of the counts per minute (cpm) in the lung lysates from three independent experiments. Statistical significance was determined by analysis of variance (ANOVA) followed by Tukey's test for multiple comparison to determine P-values.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "A Amitriptyline (2 mg/kg, Ami) was intraperitoneally injected into C57BL/6mice for five times every 12 h. Sixty minutes after the last injection, 1 × 105B16F10tumor cells were intravenously injected. Control experiments confirmed that amitriptyline inhibited Asm activity in the blood by approximately 85%. Asm heterozygous mice were injected with 1 × 105B16F10tumor cells. The number of lungmetastases was determined after 14 days. Shown is the mean ± SD from six mice each, ANOVA followed by Tukey's test for multiple comparison. P-values are indicated.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "B, C MT/ret cells (105) suspended in 200 μl Matrigel/PBS (1:1) were injected s.c. in the left and right flanks of 8-week-old Asm-deficient mice or wild-type mice. Mice were sacrificed at day 20 after injection, and spleens were inspected for the presence of metastases. The representative photographs (B) show the results from one of four experiments, and the quantitative analysis is displayed in (C).",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "B, C MT/ret cells (105) suspended in 200 μl Matrigel/PBS (1:1) were injected s.c. in the left and right flanks of 8-week-old Asm-deficient mice or wild-type mice. Mice were sacrificed at day 20 after injection, and spleens were inspected for the presence of metastases. The representative photographs (B) show the results from one of four experiments, and the quantitative analysis is displayed in (C).",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "D Platelets were isolated from wild-type or Asm-deficient mice by density-gradient centrifugation, and 1 × 107 platelets were incubated with 1 × 105 MT/ret melanoma cells. The samples were lysed, and Asm activity in cell lysates was determined. In unstimulated samples (time point 0 of co-incubation), tumorcell and platelet lysates were admixed after lysis.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "E To measure secretion of Asm by platelets, tumor cells and platelets were co-incubated for 30 s, the samples were pelleted, the supernatants were acidified, and the Asm activity was measured. All Asm activity measurements were performed in the presence of 100 μM Zn2+.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "F Local tumor growth in wild-type or Asm-deficient mice at the flank was measured at day 20.",
    "ncbi_link": "Asm: 20597"
  },
  {
    "caption": "B. BrdU-sensitized  U-2-OS cells stably expressing GFP-NLS-CDKL5  were pre-incubated with DMSO  (mock), olaparib (5 μM), talazoparib (50 nM) or PDD00017273  (0.3 μM) for 1 h prior to  micro-irradiation and live-imaging at the indicated times post-irradiation. One of three independent experiments is shown. Scale bar is 10 μm",
    "ncbi_link": "GFP: 
CDKL5: 6792"
  },
  {
    "caption": "E.  BrdU-sensitized parental or PARP1Δ/Δ, PARP2Δ/Δ,  PARP1/2Δ/Δ U-2-OS cells transiently expressing GFP  NLS-CDKL5 were subjected to 355 nm line micro-irradiation followed by time lapse imaging. One of two independent experiments is shown. Scale bar is 10 μm",
    "ncbi_link": "PARP1: 142
PARP2: 10038"
  },
  {
    "caption": "B. BrdU-sensitized U-2-OS (Flp-In T-Rex) cells stably expressing GFP-NLS, the  GFP-NLS-CDKL5 deletion mutants shown in A, or full length (FL)  GFP-NLS-CDKL5 were subjected to line  micro-irradiation (355 nm) and time lapse imaging. Three independent experiments were performed, and one representative experiment is shown. Scale bar is 10 μm",
    "ncbi_link": "GFP: 
CDKL5: 6792"
  },
  {
    "caption": "A.  HEK293 cells were co-transfected with CDKL5 (wild type \"WT\" or kinase-dead \"KD\" K42R mutant) fused to an NLS, and FLAG-ELOA (wild type \"WT\" or a S311A mutant \"SA\"). Anti-FLAG precipitates or cell extracts were probed with the antibodies indicated. One of three independent experiments is shown. B. Same as A. showing a range of pathogenic (red) and benign (blue) CDKL5  variants. ",
    "ncbi_link": "FLAG: 
CDKL5: 6792
ELOA: 6924"
  },
  {
    "caption": "(C-E). Wild type (WT), CDKL5­-disrupted (CDKL5Δ/Δ) or siRNA-transfected cells were subjected to indirect immunofluorescence analysis with the indicated antibodies at laser tracks. Quantification of  ELOA-pSer311 signal at the laser tracks is shown. Data represent mean ± SD of total pELOA Ser311 intensities in different biological replicates as indicated (n). For simplicity, only intensities greater than zero are shown. Statistical significance was assessed by one-way-ANOVA-test or unpaired t test with Welch's correction. Asterisks **** indicate P-values of <0.0001. Scale bar is 10 μm",
    "ncbi_link": "CDKL5­: 6792
CDKL5: 6792"
  },
  {
    "caption": "D. (Left) Quantification of transcription in  U-2-OS 263 IFII reporter cells from experiment in B. >150 cells were analysed per condition per experiment. The mean ± SD from four independent experiments is shown. (Right) Quantitative RT-PCR  analysis of YFP-MS2 mRNA in  U-2-OS  263 reporter cells. Data represent mean ± SD in different biological replicates as indicated (n). Statistical significance for all the data was assessed by two-way-ANOVA-test, **p<0.01, ***p<0.001 and ****p<0.0001; ns - not significant.",
    "ncbi_link": "YFP: 
IFII: 3439
MS2: 100271694"
  },
  {
    "caption": "B, C. Quantitative PCR with reverse transcription  (qRT-PCR) analysis of SLCO5a1 (B) and RYR2 expression levels (C) (left panels) U-2-OS HA-ER-I-PpoI  cells depleted of  CDKL5 transiently transfected with FLAG-tagged CDKL5 wild type (WT) or a K42R-mutated kinase dead (KD) mutant, or empty vector, at the times indicated after inducing I-PpoI. The mean ± SD from two qPCR  replicates of two independent experiments is shown. Statistical significance for all the data was assessed by two-way-ANOVA-test *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001; ns - not significant. I-PpoI-mediated cutting efficiency in the relevant gene is shown in the right-hand panel",
    "ncbi_link": "FLAG: 
HA: 
I-PpoI: 
CDKL5: 6792
RYR2: 6262
SLCO5a1: 81796"
  },
  {
    "caption": "(C) Immunoblot of WT, KO and A537T prostates probed with specific antibodies to detect ELAC2 and normalise its levels to Hsp60 that was used as a loading control (n=3). ***p= 1.09909E-07 for KO and ***p= 3.55091E-05 for A537T, Student's two-way t-test, values are means ± SD of biological replicates.",
    "ncbi_link": "ELAC2: 68626"
  },
  {
    "caption": "(E) Survival data for ELAC2 WT (n=30), KO (n=30) and A537T (n=30) mice.",
    "ncbi_link": "ELAC2: 68626"
  },
  {
    "caption": "(F) ELAC2 WT-TRAMP, KO-TRAMP and A537T-TRAMP prostates from 10- and 30-week-old mice. Bladder and seminal vesicles were removed in 10-week-old mice. Images show the typical differences between WT, KO and A537T prostates of at least 10 different mice per genotype.",
    "ncbi_link": "ELAC2: 68626"
  },
  {
    "caption": "(G) Survival data for ELAC2 WT-TRAMP (n=30), KO-TRAMP (n=30) and A537T-TRAMP (n=30) mice (biological replicates). Gehan-Breslow-Wilcoxon test showed significant difference (*p=0.045) between the WT-TRAMP and KO-TRAMP or A537T-TRAMP survival curves.",
    "ncbi_link": "ELAC2: 68626"
  },
  {
    "caption": "(A) Representative images of anterior, dorsal, ventral and lateral lobe sections from 30-week-old ELAC2 WT (n=7), KO (n=7) and A537T (n=5) mice. 5 µm sections of each lobe were cut and stained with haematoxylin and eosin.",
    "ncbi_link": "ELAC2: 68626"
  },
  {
    "caption": "WT ELAC2-EGFP or A537T ELAC2-EGFP were expressed in LNCaP cells and the associated proteins that immunoprecipitated with the EGFP antibody were detected by mass spectrometry. EGFP-only protein was used as a control. Volcano plots are showing the enriched proteins with proteins and (C) shows the proteins that have reduced or increased association with A537T ELAC2. Volcano plots comparing Log2 fold change against the -log10 p-value and significant (p < 0.05) enriched proteins are shown in red and proteins with reduced association are shown in blue for three biologically independent experiments.",
    "ncbi_link": "EGFP: 
ELAC2: 68626"
  },
  {
    "caption": "Kainic acid mouse model of TLE: Daily EEG recordings obtained from the epileptogenic focus starting from one month after KA injection and spanning the period from 2 days before to 7 days after AAV-pDyn delivery (2x109 gp).",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "A generalized seizure is depicted in Fig. EV1 D and E: The characteristic EEG features of this model, secondary generalized seizures (bars) and HPDs (lines) were reduced in number and in duration by AAV-pDyn (red; n = 3 (from day 60); 7 (till day 30) per time-interval), but not by AAV-ΔGFP or after sham treatment (blue; n = 4 (day 90); 5 (day 30 and 60); 6 (before day 30), per time-interval). The relatively high variability of seizure frequencies and duration is typical for this model and reflects the findings in human mTLE.",
    "ncbi_link": "GFP: 
pDyn: 5173"
  },
  {
    "caption": "Injection of norBNI (20 mg/kg; i.p.) results in a transient reappearance of HPDs immediately and 24 hrs after application. One week after norBNI application (washout) suppression of HPDs was re-established. Data obtained from 4 epileptic animals before (black) and after (red) AAV-pDyn delivery (2x109 gp) are depicted. *",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "EEG recordings obtained from the ipsilateral dorsal hippocampus of rats after electrical self-sustained status epilepticus (SSSE) before (black) and after (red) AAV-pDyn delivery (4x109 gp) are depicted. Spike trains with a frequency of at least 2.5 Hz induced by SSSE were markedly reduced by AAV-pDyn (n=4).",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "Spatial learning and memory was tested on the Barnes maze. Quadrant 1 (Q1) contains the target hole (red; A). Unilateral injection of AAV-pDyn (B) or AAV-eGFP (C) into naïve young adult mice (12 weeks age) did not influence the performance as compared to naïve controls (D) when tested 4 weeks after AAV injection. Mice treated two weeks after KA with AAV-pDyn (E,H) performed equally to age-matched naïve controls (D,G) 2 weeks (E) and 5.5 months (H) after treatment. By contrast, animals treated two weeks after KA with AAV-ΔGFP (F,I) gradually lost this ability. Two-way ANOVA revealed significance between AAV-ΔGFP and AAV-pDyn treated groups for interaction 2 weeks (p = 0.0349) and 5.5 months (p = 0.0311) after AAV, respectively, at each time interval and quadrant (p < 0.0001) 2 weeks after AAV. Comparison of AAV-pDyn injected with naïve animals revealed no differences.",
    "ncbi_link": "eGFP: 
GFP: 
pDyn: 5173"
  },
  {
    "caption": "epileptic mice, which were not able to learn the Barnes maze task one month after KA (J, M), AAV-pDyn application restored spatial memory one (K) and 2 months (L) after treatment.",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "epileptic mice, which were not able to learn the Barnes maze task one month after Treatment with AAV-ΔGFP did not result in improved memory (N,O).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "Double-immunofluorescence labeling is depicted for pDyn and NeuN (A-C) or GFAP (D-F) in the ipsilateral dentate gyrus of KA-treated and AAV-pDyn-injected mice. Enlarged view in (F) represents 15 x 30 µm.",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": ": mature Dyn B content (measured by a Dyn B specific EIA) in the dorsal hippocampus of mice treated with KA (blue symbols) or KA and AAV-pDyn (red symbols) 1.5 (open symbols; n = 6) and 6 (filled symbols; n = 3) months after vector treatment. Naïve animals were age matched to the 1.5 months after AAV group. iH stands for ipsilateral hippocampus and cH for contralateral hippocampus.* = p<0.05; ** = p<0.01; paired t-test was used for comparison of ipsi- and contralateral hippocampi. Two-way ANOVA was used to compare Dyn levels between the early and late time interval.",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "Mature Dyn B content in the CSF of mice treated with KA (blue symbols) or KA and AAV-pDyn (red symbols) 1.5 (open symbols; n= 6) and 7 (filled symbols; n = 4) months after vector treatment. ** = p<0.01; one-way ANOVA with Dunnett post hoc test",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "In-situ hybridization for AAV-derived pDyn mRNA at 10 weeks post AAV-pDyn delivery in the left dorsal hippocampus is depicted for a single brain at five levels between 1.1 (left) and 2.3 (right) mm from bregma. The probe specifically detects the codon-optimized sequence, therefore the contralateral side represents a control devoid of the respective mRNA.",
    "ncbi_link": "pDyn: 5173"
  },
  {
    "caption": "At 10 weeks post AAV-pDyn delivery, markers of inflammation were analyzed as follows: Relative optical densities (ROD) were evaluated from film autoradiographs after in-situ hybridization for mRNAs of inflammatory markers (Interleukin-1β (B), Interleukin-6 (C), Interleukin1a receptor agonist (D), Tumor Necrosis Factor-α (E) and Nitric Oxide Synthase-1 (F)) in 3 principal sub-regions of the hippocampus in AAV-pDyn (n=7; red) or AAV-eGFP (n=5; blue) injected animals. GC = granule cell layer; CA = cornu ammonis.",
    "ncbi_link": "eGFP: 
Interleukin-1β: 16176
Interleukin1a receptor agonist: 16181
Interleukin-6: 16193
Nitric Oxide Synthase-1: 18125
pDyn: 5173
Tumor Necrosis Factor-α: 21926"
  },
  {
    "caption": "Male C57BL/6J mice were fed with chow diet supplemented with 0, 0.5%, 1% SUC for 8 weeks. mRNA expression of MyHC I, MyHC IIa, PGC-1α, myoglobin, TnnT1 MyHC IIb, MyHC IIx and TnnT3 in the gastrocnemius muscle (n=5-6).",
    "ncbi_link": "myoglobin: 17189
MyHC I: 17879
MyHC IIx: 17879
MyHC IIa: 17882
MyHC IIb: 17884
PGC-1α: 19017
TnnT1: 21955
TnnT3: 21957"
  },
  {
    "caption": "The mRNA level of SUNCR1 in gastrocnemius and soleus (n=7-8).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "SUNCR1 protein expression in C2C12 cells transfected with vector or siSUNCR1 (n=3).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "[Ca2+]i, in vector or siSUNCR1 transfected C2C12 cells treated with 0 or 2 mM SUC (n=5-6).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "enzymes activity (n=9-10)of (J) HK, (K) LDH, and (L) SDH in vector or siSUNCR1 transfected C2C12 cells treated with 0 or 2 mM SUC (n=5-6).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. The O2 consumption (VO2), RER",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. muscle grip strength",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. four-limb handing time",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. low speed running time.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. The enzymes activity of (H) HK, (I) LDH, and (J) SDH in gastrocnemius.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. Immunoblots and quantification of MyHC-I, IIb, NFAT, and PGC-1α protein in gastrocnemius.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J or SUNCR1 KO mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. Representative images and quantification of Laminin (green), or MyHC-I and IIb (red) immunofluorescent staining in gastrocnemius muscle (n=3). Scale bar in (M) represents 100 µm.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. SUNCR1 protein expression in gastrocnemius from mice transfected with shSUNCR1 lentivirus or LV-shScrambled (n=3).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. The running time in low speed",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. four-limb handing time",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. muscle grip strength of both control and gastrocnemius-specific SUNCR1 knockdown mice.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. The enzymes activity of (F) HK, (G) LDH, (H) SDH in gastrocnemius.",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "Male C57BL/6J mice were injected with LV-shScrambled or shSUNCR1 lentivirus specifically into the gastrocnemius at 6 weeks of age. After two weeks of recovery, mice were fed with chow diet supplemented with 0 or 1% SUC for 6 weeks. Immunoblots and quantification of MyHC-I, IIb, NFAT, and PGC-1α protein in gastrocnemius (n=3).",
    "ncbi_link": "SUNCR1: 84112"
  },
  {
    "caption": "E Effect of H2A.Z.2.2 ROF on facilitating histone replacement. Incorporations of yeast H2A.Z-H2B dimers containing either the wild type H2A.Z or Z.2.2-like H2A.Z were analyzed by SWR1-catalyzed histone replacement assay. H2A.Z and Z.2.2-like H2A.Z incorporated into nucleosome were resolved by 6% Native-PAGE and detected by SYBR Green staining and western blotting.",
    "ncbi_link": "H2B: 852284///851810"
  },
  {
    "caption": "b, TG levels in vector-infected (VEC) and siAtg5 cells in RM, OL or in MCDM (*P  0.001, n = 5). OL values are in mM.",
    "ncbi_link": "Atg5: 365601"
  },
  {
    "caption": "c, TG levels in wild-type (WT) or Atg5 knockout mice embryonic fibroblasts (Atg5-/-) (*P 0.01 or **P 0.0001, n = 5).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "a, b, VEC and siAtg5 cells cultured with oleate (OL) or in MCDM were examined for their rates of TG synthesis (a) and β-oxidation (b) as compared to cells in regular medium alone (*P  0.03, **P  0.004 with VEC cells in the same medium, n = 3–4).",
    "ncbi_link": "Atg5: 365601"
  },
  {
    "caption": "D Cardiac mRNA expression levels normalized to HPRT. One-way ANOVA; n = 5 mice per ZT; ZT5 vs. ZT17: *P = 0.0064 (CXCL1), *P = 0.0007 (CXCL2), *P = 0.0007 (CXCL5), *P = 0.0001 (ICAM-1), *P = 0.0009 (VCAM-1), *P = 0.0181 (CCL3), *P = 0.0360 (CCL5).",
    "ncbi_link": "HPRT: 
CCL3: 20302
CCL5: 20304
CXCL1: 14825
CXCL2: 20310
CXCL5: 20311
ICAM-1: 15894
VCAM-1: 22329"
  },
  {
    "caption": "F Mean fluorescence intensity (MFI) of CXCX2 expression at ZT5 in the blood 24h after MI in wildtype (WT) and CXCR2 KO mice. Student`s t-test. N = 6 mice in both groups; *P = 0.0001.",
    "ncbi_link": "CXCR2: 12765"
  },
  {
    "caption": "G Percentage of CXCR2hi bloodneutrophils 24h after ZT5 or ZT13 MI in WT and CXCR2 KO mice. Two-way ANOVA followed by Bonferroni post-hoc test; for ZT5 n = 6 mice in both groups, for ZT13 n = 7 WT mice and n = 5 CXCR2 KO mice; WT vs. CXCR2 KO: *P = 0.0001 (ZT13).",
    "ncbi_link": "CXCR2: 12765"
  },
  {
    "caption": "H Flow cytometry quantification of neutrophils in hearts 24h after MI in ZT5 and ZT13 operated WT and CXCR2 KO mice. Two-way ANOVA followed by Bonferroni post-hoc test; for ZT5 n= n = 6 mice in both groups, for ZT13 n = 7 WT mice and n = 5 CXCR2 KO mice; WT vs. CXCR2 KO: *P = 0.0461 (ZT13), ns = not significant.",
    "ncbi_link": "CXCR2: 12765"
  },
  {
    "caption": "a, Electron microscopy analysis of wild-type (WT) and Smurf1-/- (KO) MEFs grown in normal media or EBSS (starvation) for 4 h. Arrowheads, representative autophagosomes; arrows, representative autolysosomes. Scale bars, 500 nm.",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "a, Representative mitochondrial morphology in Smurf1+/+ (wild-type) and Smurf1−/− (KO) MEFs transfected with indicated construct and treated with DMSO or 10 µM CCCP for 24 h. b, Quantification of percentage of total cells with a diffuse accumulation of abnormal fragmented mitochondria and lack of mitochondrial clearance. Results shown represent combined data from 3-5 experiments per condition with triplicate wells (of at least 100 cells per well) analysed for each condition per experiment. Shown are mean ± s.e.m. for average values from each experiment. Similar results were observed in each independent experiment. *P  0.001, Students t-test. c, Measurement of mitochondrial fractional area (percentage of total cellular area) in MEFs treated as in a. Results shown represent mean ± s.e.m. for 50 cells per condition.",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "d, Representative confocal micrographs of KO MEFs transfected with YFP-SMURF1 wild-type or YFP-SMURF1Dgr;C2 (Dgr;C2) and treated for 4 h with DMSO or CCCP.",
    "ncbi_link": "SMURF1: 75788"
  },
  {
    "caption": "e, Representative confocal micrographs of KO MEFs transfected with GFP-LC3 and wild-type mCherry-SMURF1 (WT) or mCherry-SMURF1Dgr;C2 (Dgr;C2) and treated for 4 h with CCCP. Inset, upper right, formation of completed autophagosome around a damaged mitochondrion associated with wild-type SMURF1; insets, lower right, incomplete autophagosomes or absence of LC3 signal around mitochondria associated with SMURF1Dgr;C2. See also Supplementary Figs 10 and 11 for enlarged images.",
    "ncbi_link": "LC3: 66734
SMURF1: 75788
SMURF1: Q9CUN6///75788"
  },
  {
    "caption": "f, Representative electron microscopy images of indicated tissues from 10-month-oldSmurf1+/+ (WT) or Smurf1-/- (KO) mice. Arrows, representative abnormal mitochondria. Scale bars, 1 µm. Similar abnormalities were observed throughout entire electron microscopy tissue section for each mouse and in tissue samples from three different mice for each genotype.",
    "ncbi_link": "Smurf1: 75788"
  },
  {
    "caption": "A Germination of dog1-3 (knock-out), WT, and dog1-5 (DOG1 upregulation) seeds in media supplemented with NaCl for the indicated number of days after stratification (DAS). Scale bar represents 5 mm. B Germination rate in 100 mM NaCl 7 days after stratification for seeds of different genotypes. Lines represent the fitted curves with a 95% confidence interval (grey area). ∗ p-value < 0.05 from two-tailed Student's t-test. Data for WT is the same as plotted in Fig 3C. C",
    "ncbi_link": "DOG1: 834623
dog1: 834623"
  },
  {
    "caption": "C shDOG1 expression levels normalized to UBC21 (AT5G25760) in dog1-3 and dog1-5 relative to WT. D shDOG1 and lgDOG1 expression levels normalized to UBC21 in seeds treated with 100 mM NaCl relative to mock. E",
    "ncbi_link": "DOG1: 834623
dog1: 834623
UBC21: 832645"
  },
  {
    "caption": "A 3'RNA-seq read coverage on DOG1 locus. Black colour is used for coverage within the scale on the right-hand side (0 to 500), and red is used for coverage within the scale on the left-hand side (0 to 50). Above is a schematic representation of the annotated transcripts from the DOG1 locus and the chromosome coordinates.",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "Germination time-course in 100 mM NaCl after stratification for puppies-1 (C) relative to WT. Lines represent fitted curves with a 95% confidence interval (grey area), dots represent data points, ∗ p-value < 0.05 from the two-tailed Student's t-test. (C) Data for WT is the same as plotted",
    "ncbi_link": "puppies-1: 823785"
  },
  {
    "caption": "F RT-qPCR fold-change induction of PUPPIES-uns, PUPPIES-prom, PUPPIES-fusion, shDOG1, and lgDOG1 in puppies-ox relative to WT (blue dashed line), in dry (light grey) and imbibed seeds in the presence of 100 mM NaCl (red). Significance from the two-tailed Student's t-test for comparing dry seeds of WT and puppies-ox is represented with light grey asterisks, and salt-imbibed seeds of WT and puppies-ox are represented with red asterisks. Black asterisks represent significance from two-way ANOVA with Tukey's multiple comparisons test for dry seeds vs imbibed seeds. ns p-value > 0.05, ∗ p-value < 0.05, ∗∗ p-value < 0.01, ∗∗∗ p-value < 0.001. Error bars represent the mean ± SD. n = 4 biological replicates.",
    "ncbi_link": "PUPPIES: 
puppies: 
DOG1: 834623"
  },
  {
    "caption": "G RT-qPCR with primers for shDOG1 and lgDOG1 on nascent RNA from seeds imbibed in 100 mM NaCl from puppies-ox relative to WT. Nascent RNA levels were normalized to UBC21. Bars and error bars represent the mean ± SD. Points represent biological replicates. Statistical significance from two-tailed Student's t-test. ∗ p-value < 0.05.",
    "ncbi_link": "puppies: 
DOG1: 834623
UBC21: 832645"
  },
  {
    "caption": "A z-stack max-projection image of smFISH for DOG1 RNA. The \"Inferno\" colour scale is used for the intensity of fluorescence from Quasar670 fluorophore (DOG1). The blue colour shows fluorescence from DAPI (nuclei staining). Arrowheads point to foci corresponding to transcription sites (TS). The scale bar is 20 μm. B Distribution of cytoplasmic DOG1 foci per cell in WT. The blue vertical dashed line indicates the average. C",
    "ncbi_link": "DOG1: 834623"
  },
  {
    "caption": "G z-stack max-projection images from seeds imbibed in 100 mM NaCl of WT (left) versus puppies-ox (right). Arrowheads point to foci corresponding to TS.",
    "ncbi_link": "puppies: "
  },
  {
    "caption": "A-E The profile of Pol II during DOG1 transcription. Plots show the fraction of unique reads from targeted NET-Seq using rolling median (11 nt). Targeted libraries for sequencing of DOG1 locus were obtained by usage of 5 primers across the gene. Pol II dynamics is analyzed separately for each region sequenced in exon 1 (A), exon 2 (B), exon 3 (C), intron 1 (D), and intron 2 (E). The x-axis shows the distance in bp from DOG1. A light red colour fill highlights the regions where Pol II density is higher in puppies-ox. A light blue colour fill highlights the regions where Pol II density is higher in WT. For each plot, coloured tiles represent the fold-change (puppies-ox / WT) on a logarithmic scale. Greyscale tiles represent the result of a statistical test for the difference between genotypes from the two-tailed Student's t-test after Bonferroni correction. Tiles correspond to a 25 bp bin each. Vertical dashed lines connect the exon boundaries on the plots with the schematics of the DOG1 gene with grey boxes representing exons and black lines representing introns.",
    "ncbi_link": "puppies: 
DOG1: 834623"
  },
  {
    "caption": "F, G RT-qPCR measurement of alternative splicing of lgDOG1 alpha and beta isoforms and unspliced intron 1 DOG1 isoforms levels in puppies-ox, and puppies-1 relative to WT, in seeds treated with 100 mM NaCl.",
    "ncbi_link": "puppies: 
puppies-1: 823785
DOG1: 834623
DOG1 alpha: 834623
beta: 834623"
  },
  {
    "caption": "D.)  Live epifluorescence microscopy of the PfMev api-EcDPCK-mCherry Δdpck parasite line that is expressing api-SFG (green) and api-EcDPCK-mCherry (red) with DAPI marking the nuclei (blue). E.) Live epifluorescence microscopy of the  PfMev api-EcDPCK-mCherry Δdpck line after treatment with 1x azithromycin for 7 days under supplementation with 50μM mevalonate. This parasite line expresses  api-SFG (green) and api-EcDPCK-mCherry (red) with DAPI marking the nuclei (blue). Data information: All microscopy images represent fields that are 10µm long by 10µm wide.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "F.) Attempted  PCR detection of the ldh,  sufB, and cox1 genes from the nuclear (N), apicoplast (A), and mitochondrial (M) genomes, respectively. We failed to amplify sufB from the azithromycin-treated (+ Azith) PfMev api-EcDPCK-mCherry Δdpck parasites, indicating the loss of the  apicoplast  organellar genome.",
    "ncbi_link": "mCherry: 
DPCK: 949060
ldh: 814112
dpck: 811997
sufB: 812100
cox1: 812199///811957"
  },
  {
    "caption": "B.) Live epifluorescence microscopy of the  PfMev EcDPCK-mCherry line. This parasite line expresses api-SFG (green) and EcDPCK-mCherry (red) with DAPI marking the nuclei  (blue). D.) Live epifluorescence microscopy of the PfMev EcDPCK-mCherry Δdpck line. This parasite line expresses api-SFG (green) and EcDPCK-mCherry (red) with DAPI marking the nuclei  (blue). Data information: All microscopy images represent fields that are 10µm long by 10µm wide.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "E.) Attempted  PCR detection of the  ldh, sufB, and cox1 genes from the nuclear (N), apicoplast  (A), and mitochondrial (M) genomes, respectively. We were successful in amplifying  sufB from the PfMev EcDPCK-mCherry Δdpck parasite line grown under continuous supplementation with 50μM mevalonate, indicating retention of the  apicoplast  organellar genome.",
    "ncbi_link": "mCherry: 
DPCK: 949060
ldh: 814112
dpck: 811997
sufB: 812100
cox1: 812199///811957"
  },
  {
    "caption": "C.)  Live epifluorescence microscopy of the PfMev CLD-EcDPCK-mCherry-apt Δdpck line. This parasite line expresses api-SFG (green) and CLD-EcDPCK-mCherry (red) with DAPI marking the nuclei (blue). This parasite line was grown in the presence of 0.5μM aTc. D.) The  PfMev CLD-EcDPCK-mCherry-apt Δdpck parasite line grown in the absence of aTc for 48 hours. The brightness of the red fluorescence image was increased to demonstrate the lack of mCherry signal associated with the parasite. E.) The PfMev CLD-EcDPCK-mCherry-apt Δdpck parasite line grown in the presence of 0.5μM aTc, and in the presence of 0.5μM Shield1 (Shld) for 48 hours. F.) The PfMev CLD-EcDPCK-mCherry-apt Δdpck parasite line grown in the absence of aTc, and in the presence of 0.5μM Shield1 (Shld) for 48 hours. The brightness of the red fluorescence image was increased to demonstrate the lack of mCherry signal associated with the parasite. Data information: All microscopy images represent fields that are 10µm long by 10µm wide.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "G.) Growth curve of the  PfMev CLD-EcDPCK-mCherry-apt Δdpck parasite line grown either in the presence of 0.5μM  aTc  and the absence 0.5μM Shield1 (permissive condition, blue), or the absence of 0.5μM  aTc and the presence of 0.5μM Shield1  (non-permissive condition, red). Pantothenate was supplied at 50nM in both conditions and the cultures were diluted 1:5 on day 4. Treatment under non-permissive conditions resulted in reduced parasite growth beginning at day 1 (two-way ANOVA, followed by Bonferroni's correction; *, P < 0.05). Error bars represent the standard error of the mean from two independent experiments, each conducted in quadruplicate.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "A.) Attempted  PCR detection of the  ldh, sufB, and cox1 genes from the  nuclear  (N), apicoplast (A), and  mitochondrial  (M) genomes, respectively. We were unsuccessful in amplifying sufB  from the  PfMev CLD-EcDPCK-mCherry-apt Δdpck  parasite line after treatment with 100nM azithromycin  (Azith) in the presence of 50μM mevalonate, indicating the disruption of the  apicoplast organelle.",
    "ncbi_link": "mCherry: 
DPCK: 949060
ldh: 814112
dpck: 811997
sufB: 812100
cox1: 812199///811957"
  },
  {
    "caption": "B.) Live epifluorescence microscopy of the apicoplast-negative PfMev CLD-EcDPCK-mCherry-apt Δdpck line post treatment with 100nM azithromycin in the presence of 50μM mevalonate. This parasite line expresses  api-SFG (green) and the CLD-EcDPCK-mCherry construct (red) with DAPI  marking the nuclei  (blue).  Images represent fields that are 10µm long by 10µm wide.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "C.) Growth curve of the PfMev CLD-EcDPCK-mCherry-apt Δdpck parasite line containing a disrupted apicoplast grown either in the presence of 0.5μM aTc and the absence 0.5μM Shield1 (permissive condition, blue), or the absence of 0.5μM aTc and the presence of 0.5μM Shield1 (non-permissive condition, red). Pantothenate (50nM) and mevalonate  (50μM) were supplied in both conditions and the cultures were diluted 1:5 on day 4. Treatment under non-permissive conditions resulted in reduced parasite growth beginning at day 2 (two-way ANOVA, followed by Bonferroni's correction; **, P < 0.01). Error bars represent the standard error of the mean from two independent experiments, each conducted in quadruplicate.",
    "ncbi_link": "mCherry: 
DPCK: 949060
dpck: 811997"
  },
  {
    "caption": "b, Representative phase images of the morphology of WT and Apc-/- organoids before mRNA isolation.",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "c, Heat map illustrating differentially expressed genes (DEGs) encoding heat shock proteins between WT and Apc-/- organoids.",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "e, f, Relative gene expression of Hspb1 (***P=0.0004, n=6)(e) and protein expression of HSP25 (f) in unrecombined versus recombined murine organoids.",
    "ncbi_link": "Hspb1: 15507"
  },
  {
    "caption": "g, Gene expression of Hspb1 in normal (N) versus adenoma (A) tissue (***P=0.0002, n=4).",
    "ncbi_link": "Hspb1: 15507"
  },
  {
    "caption": "H, RNA-ISH for Hspb1 in murine intestinal adenoma. Scalebar, 100 μm. Zoom panel, 25 μm",
    "ncbi_link": "Hspb1: 15507"
  },
  {
    "caption": "i, Relative gene expression of human HSPB1 in paired sets of normal versus adenoma tissue, (****P<0.0001, paired t-test, n=59 pairs).",
    "ncbi_link": "HSPB1: 3315"
  },
  {
    "caption": "Relative gene expression of AXIN2 (*P=0.0129), P21(*P=0.0103), and HSPB1(*P=0.0236) (b) in Ls174t-dnTCF4 cells the presence or absence of doxycycline.",
    "ncbi_link": "AXIN2: 8313
P21: 1026
HSPB1: 3315
TCF4: 6925"
  },
  {
    "caption": "protein expression of HSP27 (c) in Ls174t-dnTCF4 cells the presence or absence of doxycycline.",
    "ncbi_link": "TCF4: 6925"
  },
  {
    "caption": "Relative gene expression of Hspb1 in murine WT organoids treated with different concentrations of CHIR-99021 (**P=0.0016, one way ANOVA, n=4) (d)",
    "ncbi_link": "Hspb1: 15507"
  },
  {
    "caption": "protein expression of HSP25 in WT and Apc-/- organoids (e).",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "g, h, Representative images of single cell Hspb1 KO clones passaged after loss of Apc (g), and quantification of their clonogenic potential (*P=0.0147(#1), **P=0.0035(#2), **P=0.0032(#3)) (h).",
    "ncbi_link": "Apc: 11789
Hspb1: 15507"
  },
  {
    "caption": "i, j, Representative images of Apc-/- organoids cultured in the absence or presence of 60 μM BVDU (i), and quantification of their clonogenic potential (**P=0.0039) (j).",
    "ncbi_link": "Apc: 11789"
  },
  {
    "caption": "k, l, Relative gene expression of Wnt target genes Axin2 (**P=0.0080) and Lgr5 (*P=0.0142) in Apc-/- organoids cultured in the absence or presence of 60 μM BVDU.",
    "ncbi_link": "Apc: 11789
Axin2: 12006
Lgr5: 14160"
  },
  {
    "caption": "m, RNA-ISH for Lgr5 in control or BVDU-treated Apc-/- organoids. Scale bar, 50 μm, zoom panel 20 μm.",
    "ncbi_link": "Apc: 11789
Lgr5: 14160"
  },
  {
    "caption": "e, f, RNA-ISH for Notum reveals Apc-mutant clones in crypt bottoms of control or BVDU-treated mice (e), and quantification of the abundance of mutant crypts (n=2 mice per condition, n=5 technical replicates per mouse) (f).",
    "ncbi_link": "Apc: 11789
Notum: 77583"
  },
  {
    "caption": "g, h, Clone size distributions of Notum+ crypts in control (n=265 crypts) or BVDU-treated (n=260 crypts) mice, the average clone size and number of fixed clones are included in the figure.",
    "ncbi_link": "Notum: 77583"
  },
  {
    "caption": "(F) Western-blotting of β-catenin, Axin2 and p-GSK3β(S9) in WT or Shank3-/- primary neurons. mice and 5 batches of cells (F) per group. Mean ratio ± SEM. Two-Tailed unpaired T-test. *P<0.05. **P<0.01. ***P<0.001. WT, wild type. KO, Shank3-/- mice.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(G) Western-blotting of SFRP1 and p-β-catenin(S33) in the total proteins, and TCF7L1 in the nuclear protein of WT or Shank3-/- ACC. 3 in mice Mean ratio ± SEM. Two-Tailed unpaired T-test. *P<0.05. **P<0.01. ***P<0.001. WT, wild type. KO, Shank3-/- mice.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(D) Western-blotting of ADH1, ALDH3 and ENO1 in the ACC of WT and Shank3-/- mice. Notice the up-regulation of ADH1, ALDH3 and ENO1 in Shank3-/- ACC. 3-4 mice in (D) P<0.05. **P<0.01. ***P<0.001. WT, wild type. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(F) ECAR assay of primary WT and Shank3-/- neurons. Notice the higher ECAR values of Shank3-/- neurons upon glucose and oligomycin stimulation. 5 batches of cells *P<0.05. **P<0.01. ***P<0.001. WT, wild type. KO, Shank3-/",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(C, D) Spine density and spine subtypes in the ACC of control and β-catenin over-expressing mice. Notice the reduction of total spine density, stubby and mushroom-like spines in β-catenin over-expressing mice. 20 μm in (C Two-Tailed unpaired T-test (Spine analysis excepting mushoom analysis in D. Mann-Whitney U test (Mushroom analysis in D.",
    "ncbi_link": "β-catenin: 12387"
  },
  {
    "caption": "Patch-clamp recording of mEPSC in the ACC of control and β-catenin over-expressing mice. Both the frequency and average amplitudes of mEPSC were reduced in Wnt over-activated ACC. , 9 neurons from 3 mice in H) Social novelty and social preference scores in , H Amplitude of mEPSC in H.",
    "ncbi_link": "β-catenin: 12387"
  },
  {
    "caption": "(I) 3-chamber assay of control and β-catenin over-expressing mice. 9-10 mice (I-K) Social novelty and social preference scores in I, Two-tailed paired T-Test (Time in compartment in I).",
    "ncbi_link": "β-catenin: 12387"
  },
  {
    "caption": "ECAR assay of primary cultured control neurons (GFP+EX3) and β-catenin over-expressing neurons (CaMKII-Cre+EX3). 5 batches of cells ECAR in Max ECAR in M.",
    "ncbi_link": "GFP: 
CaMKII: 12322
Cre: 2777477
β-catenin: 12387"
  },
  {
    "caption": "(A) Typical images of Golgi staining and reconstructed neurons in the ACC of Shank3-/- mice treated with 2-DG (KO+2-DG) or vehicle (KO+Veh). Sholl analysis of pyramidal neurons in the ACC of Shank3-/- mice treated with 2-DG or vehicle. Bar = 50 μm in (A) N = 24-28 neurons from 4 mice in KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(G) Western-blotting of GluR1, PSD95 and Homer1 in the total proteins of Shank3-/- ACC with or without 2-DG treatment. 3 mice in (G) KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "resident-intruder assay of Shank3-/- mice treated with 2-DG or vehicle. Notice the improvement of social preference and social interaction by 2-DG treatment. 10-12 mice in KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(A) ECAR assay of primary Shank3-/- neurons treated with or without XAV939. Notice the lower levels of glycolysis in XAV939 treated cells. (B) ECAR assay of primary Shank3-/- neurons treated with or without ICG-001. N = 4-5 batches of cells in Two-Tailed unpaired t-test *P<0.05. **P<0.01. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(E) Double-immunostaining of ENO1/Axin2 in WT neurons, Shank3-/- neurons, and XAV939 treated Shank3-/- neurons. Notice the colocalization of Axin2/ENO1-immunoreactivity in Shank3-/- neurons and the membrane localization of Axin2-immunoreactivity in XAV939 treated Shank3-/- neurons. Arrows point to membrane Axin2-immunoreactivity. Bar = 5 μm in E. WT, wild type. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(G) Protein CO-IP of Axin2/ENO1 in WT and Shank3-/- neurons treated with or without XAV939. Notice the strong interaction of Axin2/ENO1 in Shank3-/- neurons and diminished interaction upon XAV939 treatment. per group and 3 samples from 9 mice per group in One-way ANOVA with Tukey's multiple-comparison test WT, wild type. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "Spine length, spine density and spine subtypes of Shank3-/- ACC neurons treated with or without XAV939. Notice the increase of total spine density, stubby and mushroom-like spines and the decrease of average spine length in XAV939 treated Shank3-/- mice. 32 spines from 3 mice in Filopodia analysis in F. Spines analysis excepting filopodia analysis in F. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(H) Western-blotting of p-PSD95 and Homer1 in WT and Shank3-/- ACC treated with or without XAV939. 4-6 mice in One-way ANOVA with Tukey's multiple-comparison test WT, wild type. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(I, J) Western-blotting of GluR1 in the total and membrane protein of WT and Shank3-/- neurons treated with or without XAV939. Notice the rescuing effects of XAV939 on the expression of GluR1 in Shank3-/- neurons. 4-6 mice in and 3 samples from 12 mice in (J) per group. One-way ANOVA with Tukey's multiple-comparison test WT, wild type. KO, Shank3-/-.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "Calcium response of WT and Shank3-/- neurons treated with or without XAV939. Notice that XAV939 treatment significantly restored the amplitude, rising and decay time of calcium response in Shank3-/- neurons. Bar = 15 μm in (A) and 30 μm in magnified images of (A). N = 39 neurons from 3 batches of cells in Kruskal-Wallis H test with Dunn's multiple-comparison test KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "Calcium response of WT and Shank3-/- neurons treated with or without XAV939. Notice that XAV939 treatment significantly restored the amplitude, rising and decay time of calcium response in Shank3-/- neurons. N = 39 neurons from 3 batches of cells in Dunn's multiple-comparison test KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(D) Patch-clamp recording of mEPSCs in Shank3-/- ACC treated with or without XAV939. Both the frequency and amplitude of Shank3-/- neurons were increased by XAV939. , 7-8 neurons from 3 mice in (D) KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "resident-intruder assays of Shank3-/- mice treated with or without XAV939. Notice the improvement of social preference, social novelty and social interaction of Shank3-/- mice by XAV939 treatment. 8-10 mice KO, Shank3-/-. Veh, vehicle.",
    "ncbi_link": "Shank3: 58234"
  },
  {
    "caption": "(B) Western-blotting of β-catenin, p-β-catenin(S33), GSK-3β, p-GSK-3β(S9) and TCF7L1 in neurons derived from WT or Shank3 mutant human ESCs. Notice the similar change of Wnt signaling components as in Shank3-/- mice. N = 3-4 batches of cells in Mean ratio ± SEM. Two-tailed unpaired t-test (Wnt components expression excepting TCF7L1 and GSK3β in Mann-Whitney U test (TCF7L1 expression in B). Welch's t-test (GSK3β expression in B). WT, wild type. KO, Shank3-",
    "ncbi_link": "Shank3: 85358
Shank3: 58234"
  },
  {
    "caption": "(C) Protein CO-IP assay of Axin2/ENO1 in WT and Shank3 mutant human NPCs. (D) Protein CO-IP assay of Axin2/ENO1 in WT and Shank3 mutant human neurons. Notice the strong interaction of Axin2/ENO1 Shank3 mutant human neurons. N = 3-4 batches of cells in WT, wild type. KO, Shank3-/ NPC, neural progenitor cell.  ",
    "ncbi_link": "Shank3: 85358"
  },
  {
    "caption": "Luciferase activity was quantified in lysates of RAW 264.7 cells transfected with pGL3 basic vector harboring wild-type (wt) or mutated (mut1 or 2) IL-23p19 promoter. Transfected cells were pre-treated with JNKi (SP600125, 25 µM, 1h) and stimulated with IMQ (6h). Results are shown as fold change to pGL-3-wt transfected, LAL (Limulus amebocyte lysate) treated RAW264.7 cells. (n = 4; 2 independent experiments).",
    "ncbi_link": "IL-23: 83430
JNK: 26414///104771///26420"
  },
  {
    "caption": "DC subsets (cDC1, cDC2), Macrophages (MP) and Langerhans cells (LC) were sorted from IMQ treated back skin (5h). c-Jun, Ccl2 and Il23p19 mRNA was analyzed by qRT-PCR. Sort strategy is shown in (B). (10 mice were pooled per condition, 1 experiment).",
    "ncbi_link": "Ccl2: 20296
Il23: 83430
c-Jun: 16476"
  },
  {
    "caption": "A) Assessment of the detection limit of synthetic SARS-CoV-2 by the CRISPR-based assay, inferred from fluorescence values after 30 min. Background subtracted fluorescence represents sample minus control fluorescence without target.",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "Detection of synthetic SARS-CoV-2 RNA using commercially available paper strips (lateral-flow) in buffer (B)",
    "ncbi_link": "SARS-CoV-2: "
  },
  {
    "caption": "Detection of synthetic SARS-CoV-2 RNA using commercially available paper strips (lateral-flow) in saliva (C).",
    "ncbi_link": "SARS-CoV-2: "
  },
  {
    "caption": "(a) Genomic deletion of Atg7 in H-2Db-gp33+ T cells and in total activated (CD44hiCD62Llo) CD8+ T cells from Atg7fl/fl mice (Cre −) and Atg7fl/flGzmb-Cremice (Cre +) at day 8 after infection with LCMV Armstrong strain; results are presented relative to those of Atg7fl/fl mice, set as 100%. Each symbol represents an individual mouse; small horizontal lines indicate the mean (±s.e.m.).",
    "ncbi_link": "Cre: 
Atg7: 74244
Gzmb: 14939"
  },
  {
    "caption": "(b) Immunoblot analysis of Atg7 and the products of its enzymatic activity (left margin) in CD44hiCD62Llo CD8+ T cells isolated at day 8 after infection as in a; β-actin serves as a loading control.",
    "ncbi_link": "Atg7: 74244"
  },
  {
    "caption": "(a) Flow cytometry of circulating LCMV-specific CD8+ T cells among peripheral blood mononuclear cells from Atg5fl/fl and Atg5fl/flGzmb-Cremice on days 8, 15 and 50 after infection with LCMV Armstrong strain. Numbers adjacent to outlined areas indicate percent H-2Db-gp33+ T cells, gated on CD8+ T cells. (b) Longitudinal kinetics of the appearance of H-2Db-gp33+ T cells in the peripheral blood of mice as in a (left), and percent H-2Db-gp33+ CD8+ T cells remaining on day 15 (right) (all presented as in Fig. 4h).",
    "ncbi_link": "Cre: 
Atg5: 11793
Gzmb: 14939"
  },
  {
    "caption": "(a,b) Flow cytometry of CD8+ T cell obtained from chimeras generated (as in Supplementary Fig. 5a) by reconstitution of wild-type mice with a mixture of bone marrow cells from Atg7fl/fl C57BL/6 and wild-type C57BL/6C57BL/6 (Atg7fl/fl vs C57BL/6) or from Atg7fl/flGzmb-Cremice and wild-type C57BL/6mice and (Atg7fl/flGzmb-Cre vs C57BL/6), gated (far left) as populations specific for H-2Db-gp33 (a) or H-2Db-NP396 (b) and then assessed, on days 8, 15 and 30 after infection of recipients with LCMV Armstrong infection, as CD45.2+ (Atg7fl/fl or Atg7fl/flGzmb-Cre) donor cells or CD45.1+ (C57BL/6) donor cells (middle). Far right, appearance of tetramer-positive T cells (key, donor source) in the peripheral blood of chimeras from day 8 to day 30 after infection, presented relative to that at day 8 after infection, set as 100%.",
    "ncbi_link": "Cre: 
Atg7: 74244
Gzmb: 14939"
  },
  {
    "caption": "(a) Kinetics of the appearance of H-2Db-gp276+ T cells in the peripheral blood of Atg7fl/fl and Atg7fl/flGzmb-Cre mice at various times (horizontal axis) after infection with LCMV clone 13.",
    "ncbi_link": "Cre: 
Atg7: 74244
Gzmb: 14939"
  },
  {
    "caption": "(A) Representative image of a typical young WT cortico-hippocampal slice (350 µm) from co-culture (14 DIV) stained with DAPI (gray) to visualize nuclei (left). Dentate gyrus (DG), cornus ammonis 1 (CA1) and cortical (CTX) regions are indicated. An example of the co-culture dish is shown on the right. Co-culture includes 2 young WT (*, young co-culture) and 2 old APPPS1 (+, old co-culture) brain slices.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(B) Immunofluorescence analysis of young WT and old APPPS1 slices cultured alone (young alone, old alone) or in co-culture (young co-culture, old co-culture) at 7 days in vitro (DIV) stained with propidium iodide (PI, red) reveals reduced cell viability in old brain slices compared to young.(C) Quantitative analysis of PI positive cells in young WT and old APPPS1 slices cultured alone (white and black bars, respectively) or in co-culture (grey and white squared bars, respectively) at 7 and 14 DIV. The values are expressed as percentages of PI positive cells from the total number of DAPI positive cells. The values represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (n.s.= not significant; ***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(D-F) Immunofluorescence analysis of young WT and old APPPS1 slices cultured alone or in co-culture at 7 DIV and immunostained using neuronal (NeuN), astrocytic (GFAP) and microglial (CD68) markers (green) reveals reduced NeuN and GFAP and increased CD68 immunosignal. Scale bar: 75 µm",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A) Immunofluorescence analysis of the old APPPS1 slice in co-culture using antibody 6E10 to detect amyloid plaques (green) and Thiazine Red (TR, red) to visualize fibrillar amyloid cores. At 7 DIV, the majority of amyloid plaques contain 6E10 and TR positive dense core surrounded by 6E10 positive halo of diffuse Aβ. In contrast, at 14 DIV, the majority of amyloid plaques are core-only plaques co-stained with 6E10 and TR without detectable 6E10 positive halo. Lower panels are higher magnification images of boxed regions. Scale bars: 50 µm.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(B) Quantitative analysis of core-only plaques in old APPPS1 slices cultured alone (white bars) or in co-culture (gray bars) at 7 and 14 DIV reveals an increased number of core-only plaques upon co-culturing of old APPPS1 brain slices together with young WT slices. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques. The values represent mean ± SEM from 3 independent experiments, each experiment including 3 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(C) Western blot analysis of Aβ levels (triplicates) in the old APPPS1 tissue cultured alone or in co-culture with the young WT (14 DIV) using 2D8 antibody.(D) Quantification of Western blot signals reveals decreased levels of Aβ upon co-culturing compared to old tissue cultured alone. The values are normalized to the levels of Aβ in the old tissue cultured alone and represent mean ± SEM from 2 independent experiments, each experiment was performed in triplicates (**P < 0.01).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A, B) Immunofluorescence analysis of the old APPPS1 slice in co-culture (14 DIV) using antibodies 6E10 (green) and CD68 (red). Nuclei were counterstained using DAPI (blue). Image of boxed region in A is depicted at higher magnification in B and reveals clustering of several CD68 positive cells around amyloid plaques. Scale bars: 100 µm (A) and 10 µm (B).(C) Quantitative analysis of plaque-associated CD68 positive cells in co-culture samples at 7 and 14 DIV reveals a trend towards increased number of CD68 positive cells. The values represent mean ± SEM from at least 3 independent experiments, including total of at least 6 independent slice culture dishes (n.s.= not significant).(D) Quantitative analysis of co-culture samples at 7 and 14 DIV reveals a decrease in plaque size. The values represent mean ± SEM from at least 3 independent experiments, including total of at least 6 replicates (***P < 0.001).(E) Quantitative analysis of plaques surrounded by CD68 positive cells (clustered plaques) in co-culture samples at 7 and 14 DIV reveals an increase in the number of clustered plaques. The values are expressed as percentages of clustered plaques from the total number of amyloid plaques. The values represent mean ± SEM from at least 3 independent experiments, including total of at least 6 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(F) Immunofluorescence analysis of the old APPPS1 slice in co-culture (14 DIV) treated with cytochalasin D (CytoD) and vehicle control (Ctr) and immunostained with M3.2 (green) and CD68 (red). Inhibition of phagocytosis by CytoD blocks amyloid plaque clearance. Scale bar: 50 µm.(G) Quantitative analysis of core-only plaques in the old APPPS1 slice in co-culture (14 DIV) treated with CytoD and Ctr reveals a decreased number of core-only plaques upon CytoD treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques. The values represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Either young WT (A, B) or old APPPS1 (C-E) tissue was treated with clodronate (Clo) to remove CD68 positive cells or vehicle Ctr from 1 until 7 DIV. Treatment was stopped and subsequently old (A, B) or young (C-E) tissue was added to the culture as schematically indicated in A and C. and analyzed 14 days after. Removal of CD68 positive cells in either young WT or old APPPS1 tissue prevents amyloid plaque clearance in the co-culture model.(A) Immunofluorescence analysis of the old APPPS1 slice co-cultured with the young WT slice pre-treated with Clo and Ctr and immunostained with CD68 (red) and M3.2 (green). Scale bar: 50 µm.(B) Quantitative analysis of core-only plaques in the old APPPS1 tissue co-cultured with the young WT tissue pre-treated with Clo and Ctr as indicated in A reveals a decreased number of core-only plaques upon Clo treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (***P < 0.001).(C) Immunofluorescence analysis of the old APPPS1 slice treated with Clo and Ctr and subsequently co-cultured with the young WT slice and immunostained with CD68 (red) and M3.2 (green). Scale bar: 50 µm.(D) Area of CD68 positive cells (CD68 coverage) in the old APPPS1 tissue treated with Clo and Ctr and subsequently co-cultured with the young WT tissue as indicated in C. CD68 coverage is reduced upon Clo treatment. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (***P < 0.001).(E) Quantitative analysis of core-only plaques in the old APPPS1 tissue treated with Clo and Ctr and subsequently co-cultured with the young WT tissue as indicated in C reveals a decreased number of core-only plaques upon Clo treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, including total of 6 independent slice culture dishes (**P < 0.01).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A) Immunofluorescence analysis of the old APPPS1 slice in co-culture with the young CX3CR1+/GFP slice (14 DIV) and immunostained using GFP (green), CD68 (red) and M3.2 (blue) reveals no co-localization of young, GFP positive microglial cells with CD68 positive cells surrounding amyloid plaques. A GFP antibody was used to amplify the signal of GFP-expressing young microglial cells.(B) Immunofluorescence analysis of the old APPPS1/CX3CR1+/GFP slice in co-culture with the young WT slice (14 DIV) and immunostained using GFP (green), CD68 (red) and M3.2 (blue) reveals co-localization of old, GFP positive microglial cells with CD68 positive cells surrounding amyloid plaques. A GFP antibody was used to amplify the signal of GFP-expressing old microglial cells. Scale bar: 10 µm (A and B).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(C) 3D reconstruction of the old APPPS1/CX3CR1+/GFP slice in co-culture with the young WT slice (10 DIV) and immunostained using GFP (green) and M3.2 (red). GFP positive old microglial cells surrounding amyloid plaques exhibit intracellular M3.2 positive immunoreactivity indicative of Aβ uptake. Overview at low magnification is shown in the left panel. Scale bar: 15 µm. A detailed plaque is shown at higher magnification in the right panels. Scale bar: 10 µm.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(D) Immunofluorescence analysis of young CX3CR1+/GFP and old APPPS1/CX3CR1+/GFP slices freshly cut (0 DIV), cultured alone or in co-culture (10 DIV) and immunostained using GFP (green) shows alterations in microglial morphology of old cells upon culturing. Upper-left panels are enlargements of boxed regions. A GFP antibody was used to amplify the signal of GFP-expressing old microglial cells. Scale bars: 50 µm.(E) Quantitative analysis of amoeboid microglial cells in young CX3CR1+/GFP (white bars) and old APPPS1/CX3CR1+/GFP (green bars) brain slices freshly cut (0 DIV), cultured alone or in co-culture (10 DIV). The values are expressed as percentages of amoeboid microglia from the total number of microglial cells. The values represent mean ± SEM from 3 independent experiments, each experiment including at least 250 cells per condition (*P < 0.05, ***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A) Old APPPS1 tissue was cultured alone (old alone, white bars) or incubated with conditioned media (CM) collected from young WT slices (old alone + young CM, grey bars). Analysis included co-culture of old APPPS1 and young WT brain slices (old co-culture, black bars) as a positive control and old APPPS1 tissue incubated with conditioned media collected from old APPPS1 slices (old alone + old CM, white squared bars) as a negative control. Quantitative analysis at 7, 11 and 14 DIV reveals increased numbers of core-only plaques upon incubation of the old APPPS1 tissue with conditioned media collected from young WT slices, fully recapitulating core-only plaque numbers observed in the co-culture. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including at least 2 independent slice culture dishes (n.s.= not significant, **P <0.01, ***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(B) Old APPPS1 tissue was incubated with conditioned media collected from young WT slices previously treated with clodronate (old alone + young CM + Clo, grey bars ) and vehicle control (old alone + young CM + Ctr, white bars). Quantitative analysis at 7, 11 and 14 DIV reveals decreased numbers of core-only plaques upon incubation of the old APPPS1 tissue with conditioned media collected from young WT slices pre-treated with Clo. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including at least 2 independent slice culture dishes (n.s.= not significant, ***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(C) Old APPPS1 tissue was incubated with conditioned media collected from cultured WT primary microglial cells (old alone + MG CM, grey bar) or with unconditioned slice culture media as a control (old alone + Ctr, white bar). Quantitative analysis of core-only plaques at 14 DIV reveals enhanced amyloid plaque clearance upon incubation of the old APPPS1 tissue with conditioned media collected from cultured primary microglia. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P < 0.05).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A-F) Immunofluorescence analysis of the old APPPS1 slice (14 DIV) treated with vehicle Ctr in A, anti-inflammatory factors IL-10 and TGF-β in B and C and pro-inflammatory factors IL-6, IL-12/p40 and GM-CSF in D, E and F, respectively and immunostained with CD68 (red) and M3.2 (green). In contrast to increased number of core-only plaques upon GM-CSF treatment, other factors tested did not induce amyloid plaque clearance, resulting in a better preservation of the M3.2 positive halos of Aβ surrounding dense core of amyloid plaques. Scale bar: 50 µm.",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(A) CD68 coverage in the old APPPS1 tissue (14 DIV) treated with GM-CSF and vehicle Ctr. CD68 coverage is increased upon treatment with GM-CSF. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P < 0.05).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(B) Quantitative analysis of core-only plaques in the old APPPS1 tissue (14 DIV) treated with GM-CSF and Ctr reveals an increased number of core-only plaques upon treatment with GM-CSF. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including 3 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(C) CD68 coverage in the old APPPS1 tissue (14 DIV) incubated with conditioned media collected from young WT slices (young CM) or with non-conditioned slice culture media (Ctr). CD68 coverage is increased upon incubation of the APPPS1 tissue with the young CM. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (**P < 0.01).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(D) Immunofluorescence analysis of the old APPPS1 slice cultured alone (old alone) or in co-culture with young GM-CSF-/- brain slices (old co-culture) at 14 DIV and immunostained with CD68 (red) and M3.2 (green) reveals an increased number of core-only plaques upon co-culturing with young GM-CSF-/- brain slices. Scale bar: 50 µm.(E) Quantitative analysis of core-only plaques in the old APPPS1 slice cultured alone or in co-culture with young GM-CSF-/- brain slices (14 DIV) reveals an increased number of core-only plaques upon co-culturing of old APPPS1 brain slices together with young GM-CSF-/- brain slices. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques. The values represent mean ± SEM from 3 independent experiments, each experiment including 3 independent slice culture dishes (***P < 0.001).(F) CD68 coverage in the old APPPS1 tissue (14 DIV) cultured alone or in co-culture with young GM-CSF-/- brain slices. CD68 coverage is increased upon co-culturing of old APPPS1 brain slices together with young GM-CSF-/- brain slices. The values are normalized to CD68 coverage of the old slice cultured alone and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P < 0.05).",
    "ncbi_link": "APP: 351
GM-CSF: 12981
PS1: 5663"
  },
  {
    "caption": "(A) Immunofluorescence analysis of the old APPPS1 slice (14 DIV) treated with GM-CSF and vehicle Ctr and immunostained with CD68 (red), cell proliferation marker Ki67 (green) and M3.2 (blue). Scale bar: 50 µm.(B) Quantitative analysis of Ki67 and CD68 double positive microglial cells in the old APPPS1 tissue (14 DIV) treated with GM-CSF and Ctr reveals increased microglial proliferation upon treatment with GM-CSF. The values are expressed as percentages of CD68 and Ki67 double positive microglial cells from the total number of CD68 positive cells and represent mean ± SEM from 2 independent experiments, each experiment including 4 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(C) Immunofluorescence analysis of the old APPPS1 tissue cultured alone or in co-culture with young WT brain slices (14 DIV) and immunostained with CD68 (red), Ki67 (green) and M3.2 (blue) Scale bar: 50 µm.(D) Quantitative analysis of Ki67 and CD68 double positive microglial cells in the old APPPS1 tissue cultured alone or in co-culture with young brain slices (14 DIV) reveals increased microglial proliferation upon co-culturing of old and young brain slices. The values are expressed as percentages of CD68 and Ki67 double positive microglial cells from the total number of CD68 positive cells and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (**P < 0.01).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "(E) Old APPPS1 tissue was incubated with conditioned media collected from young WT slices and in addition treated with proliferation inhibitor AraC (young CM + AraC) or vehicle Ctr (young CM + Ctr). Immunofluorescence analysis was performed at 14 DIV using CD68 (red) and M3.2 (green). Scale bar: 50 µm.(F) Quantitative analysis of core-only plaques in the old APPPS1 tissue (14 DIV) incubated with conditioned media from young WT slices and in addition treated with AraC or Ctr reveals a decreased number of core-only plaques upon AraC treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each including 2 independent slice culture dishes (***P < 0.001).",
    "ncbi_link": "APP: 351
PS1: 5663"
  },
  {
    "caption": "Time-course analysis of mouse or NMR fibroblasts after DXR treatment qRT-PCR analysis of the expression of INK4a (F) normalized to ACTB mRNA levels",
    "ncbi_link": "INK4a: 
ACTB: 101717255"
  },
  {
    "caption": "qRT-PCR analysis of the expression of INK4a (J) in shINK4a-transduced NMR fibroblasts at 21 days after DXR treatment.",
    "ncbi_link": "INK4a: "
  },
  {
    "caption": "quantification of Annexin V-positive cells (%) (K) in shINK4a-transduced NMR fibroblasts at 21 days after DXR treatment.",
    "ncbi_link": "INK4a: "
  },
  {
    "caption": "(B) qRT-PCR analysis of the expression of INK4a at 12 days after INK4a or mock transduction, normalized to ACTB mRNA levels.",
    "ncbi_link": "ACTB: 11461
INK4a: 12578"
  },
  {
    "caption": "(C) Cell morphology and SA-β-Gal activity of mouse or NMR fibroblasts 12 days after INK4a transduction. Arrowheads indicate dying cells. ​​The number in the upper left corner indicates Hoechst-positive nuclei. Scale bar, 100 μm.",
    "ncbi_link": "INK4a: 12578"
  },
  {
    "caption": "(F) Western blot analysis of RB in mouse or NMR fibroblasts at 12 days after INK4a transduction (p, phospho-specific antibody). ACTIN was used as a loading control. The arrowhead indicates a non-specific band.",
    "ncbi_link": "INK4a: 12578"
  },
  {
    "caption": "(I) SA-β-Gal activity in the adherent living cell population and floating dead cell population in mouse or NMR fibroblast cultures at 12 days after INK4a transduction. Scale bar, 100 μm. (J) Quantification of SA-β-Gal-positive cells in the adherent living cell population and floating dead cell population after the same treatment as in I.",
    "ncbi_link": "INK4a: 12578"
  },
  {
    "caption": "(C and D) Quantification of SA-β-Gal-positive cells (%) (C) and Annexin V-positive cells (%) (Annexin V+/PI- as early apoptotic and Annexin V+/PI+ double-positive as late apoptotic) (D) in NMR-fibroblasts transduced with different forms of SV40 Large T antigen (LT, LT∆, and LTK1) and INK4a. OE; overexpression.",
    "ncbi_link": "INK4a: 
Large T antigen: 29031019
LT: 29031019"
  },
  {
    "caption": "(F) Quantification of SA-β-Gal-positive cells (%) at 21 days after DXR treatment in NMR-fibroblasts transduced with different forms of SV40 Large T antigen (LT, LT∆, and LTK1). (G) Quantification of Annexin V-positive cells after the same treatment as in F. Annexin V+/PI- cells were counted as early apoptotic cells and Annexin V+/PI- cells as late apoptotic cells.",
    "ncbi_link": "Large T antigen: 29031019
LT: 29031019"
  },
  {
    "caption": "(B) Left, representative images of lipid peroxidation (green) staining in NMR fibroblasts at 12 days after INK4a-transduction. Scale bar, 50 μm. Right, quantification of signal intensity of lipid peroxidation staining. Data are expressed as the mean ± SD from n = 3 biological replicates.",
    "ncbi_link": "INK4a: "
  },
  {
    "caption": "(C) Quantification of PI-positive cells in NMR fibroblasts treated for 24 h with N-acetyl L-cysteine (NAC), Trolox, or Tempol at 20 days after INK4a transduction (%). Data are expressed as the mean ± SD from n = 6 biological replicates except for Trolox and Tempol (n = 4).",
    "ncbi_link": "INK4a: "
  },
  {
    "caption": "(D) Western blot of monoamine oxidase (MAO)-A and MAO-B in mouse or NMR fibroblasts at 20 days after INK4a transduction. ACTIN was used as a loading control. Numbers below the gel images indicate quantification of MAO-A or -B/ACTIN intensity (n = 3 average).",
    "ncbi_link": "INK4a: 12578"
  },
  {
    "caption": "(B) qRT-PCR analysis of INK4a expression in the skin, muscle, and white adipose tissue (WAT) of 6-week-old mice (young; 6 w), 1-year-old mice (middle-aged; 1 y), 1-year-old NMRs (young; 1 y), and 15-year-old NMRs (middle-aged; 15 y).",
    "ncbi_link": "INK4a: 12578"
  },
  {
    "caption": "Time-course analysis of mice or NMR lungs after Bleo administration: qRT-PCR analysis of the expression of INK4a normalized to ACTB mRNA levels (F)",
    "ncbi_link": "ACTB: 11461
INK4a: 12578"
  },
  {
    "caption": "qRT-PCR analysis of INK4a expression normalized to ACTB mRNA levels (D) in mouse or NMR lungs at 21 days after Bleo administration, with or without Phe.",
    "ncbi_link": "ACTB: 11461
INK4a: 12578"
  },
  {
    "caption": "(A) Illustration of the crossing and ageing scheme used to obtain total RNA extracts from fly heads for the transcriptional profiling and all successive qPCR assays. Expression of different Atrophin forms with the GMR driver was induced, owing to a temperature‐sensitive mutant Gal80 repressor. F1 flies were allowed to develop at 18°C; at this temperature the Gal80 repressor keeps transgenes silent. Newly eclosed flies (0-48 h) were collected and killed immediately (0d) or aged for 2 or 14 days at 29°C. This inactivates Gal80 and transgenes are switched on by GMR‐Gal4. This protocol allows comparing siblings that differ exclusively in their age and transgenes expression. Control flies crossed to GMR‐Gal4; UbiGal80ts in all experiments are from the w1118 stock in which all UAS transgenes have been generated.",
    "ncbi_link": "UAS: 
Gal4: 855828
GMR: 855828
Gal80: 854954
Atrophin: 46156"
  },
  {
    "caption": "(B) Tangential eye sections of flies representative of all the different populations used in the microarray analysis at all different time points. Weak degeneration is only visible after 14 days with polyQ Atro; in particular with Atro75QN there is an initial loss of photoreceptors (PR, arrow), 30.7% of the ommatidia has lost at least 1 PR, that is only 5.1% of all neuronal PR have been lost at this stage (N=333).",
    "ncbi_link": "Atro: 46156"
  },
  {
    "caption": "(A) Heat maps for three subsets of the pattern clustering analysis generated using the Euclidean Distance metric. Upregulated genes are in red and downregulated genes are in green. The downregulating transcriptional activity increases with time. The main branch in clustering of the different Atro mutants is along time points. See also Supplementary Figure 4.",
    "ncbi_link": "Atro: 46156"
  },
  {
    "caption": "(B) qPCR analysis of the enrichment±s.d. of different regions of the ft regulatory elements in ChIP for Atro from BG3neuronal cell extracts. Enrichment is calculated as the percentage of DNAimmunoprecipitated from extracts of cells in which Atro expression has been induced, with respect to the amount immunoprecipitated from uninduced cell extracts according to the (Atro-No Ab)induced/(Atro−No Ab)uninduced formula. The DNA region from IV chromosome has been previously shown not to be immunoprecipitated in ChIP for Atro ( Haecker et al, 2007) and has been used as a negative control.",
    "ncbi_link": "ft: 33627
Atro: 46156"
  },
  {
    "caption": "(C) Histograms showing the number of ommatidia with a full complement (7) of PR in flies expressing Atro75QN with the Rhodopsin1 driver in either a control (w1118) or different mutant backgrounds and aged at 29°C for 28 days. Heterozygosis for two independent ft alleles and a sav allele significantly enhances the loss of PR. Mild overexpression of Wts via a GMR-wts transgene, which does not display any strong phenotype per se, significantly suppresses the loss of PR. No interaction was detected in this assay with wtsx1 and ykiB5 alleles in heterozygosity. N=430-963 from at least four eyes.",
    "ncbi_link": "ft: 33627
GMR: 855828
Atro: 46156
Rhodopsin1: 42367
sav: 252554
Wts: 43651
wts: 43651
yki: 37851"
  },
  {
    "caption": "(D) Tangential eye sections and histograms showing the degeneration of GMR>Atro75QN, Ubi-Gal80ts flies in combination with different UAS transgenes and aged 14 days as in Figure 1A. UAS-EGFP is used as a negative control. Either Ft or Wts overexpression strongly suppresses loss of PR caused by Atro75QN. Lower panels are provided as examples of quantification. A more modest but still significant rescue is observed by overexpressing a Yki RNAi contruct or Hpo; however, in this case it is to be considered that the overexpression of Hpoper se brings about the loss of at least one PR in ∼5% of ommatidia (data not shown). No effect is detected with overexpression of Sav. Two‐tailed t‐test: *P0.05; **P0.01. The wtsEPG4808 is a previously uncharacterised EP element insertion at the 5′ of the wts gene. Rare homozygous escapers display larger eyes, whereas in combination with GMR-GMR this line gives rise to smaller rough eyes, and, finally, GMR analysis of GMR>wtsEPG4808 indicates a 10‐fold increase in the head content of wts mRNA (data not shown).",
    "ncbi_link": "EGFP: 
UAS: 
Ft: 33627
GMR: 855828
Gal80: 854954
Atro: 46156
Hpo: 37247
Sav: 252554
Wts: 43651
wts: 43651
Yki: 37851"
  },
  {
    "caption": "(A) Tangential eye sections through ftfd clones aged 1, 7 and 14 days, of ftfd,dDGC13 double mutant clones and of ftfd clones in a ykiB5 heterozygous background aged 14 days. Clones are marked by the absence of yellow pigment. Arrows point at degenerating photoreceptors, arrowheads point at intact wt photoreceptors in mosaic ommatidia. The circled ommatidium is genetically wt but non‐autonomously flipped in its polarity and has not degenerated. Lower panels are masks that show clonal borders and quantification of PR number per ommatidia. After 14 days, almost all ftfd cells have degenerated, whereas almost all ftfd,dDGC13 and some ftfd,ykiB5/+ neuronalphotoreceptors have not.",
    "ncbi_link": "ft: 33627
yki: 37851"
  },
  {
    "caption": "(B) Histograms showing the quantification of degeneration in ftfd, ftfddDGC13 and ftfdykiB5/+ clones. Loss of ft leads to statistically significant loss of neurons and this is suppressed at 14 days by ykiB5and much more dramatically by dDGC13. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test.",
    "ncbi_link": "d: 33245
ft: 33627
yki: 37851"
  },
  {
    "caption": "(C) Degeneration in mosaic ommatidia in ftfd clones. At this stage of degeneration approximately half of the non‐pigmented (genotypically mutant) PR cells display a degenerative phenotype, whereas virtually all pigmented (genotypically wt) PR cells are normal. χ2‐test: 82.38; P0.001. Total PR N=310 (pigmented) and 327 (not pigmented).",
    "ncbi_link": "ft: 33627"
  },
  {
    "caption": "(D) Tangential eye sections through MARCM clone mutants for ftfd that express either no transgene or an RNAi construct against yki (UAS-ykiIR) with Tub-Gal4 and aged 14 days at 29°C. Because the transgene UAS-ykiIR is on chromosomal arm 2 L, the same as ft, clones generated with this system carry two copies of UAS-ykiIR and therefore downregulate yki very effectively. No other cell outside the clones expresses the construct and is therefore wt for yki. Mask panel is presented on the right of each section. A quantification of photoreceptor numbers (far right) displays a very significant increase in the number of wt ommatidia (N=210 and 219 from four eyes). ***P0.001 in two‐tailed t‐test. If all classes of ommatidia are considered, χ2‐test=232.30; P0.001 for 3 degrees of freedom.",
    "ncbi_link": "UAS: 
ft: 33627
Gal4: 855828
Tub: 40554
yki: 37851"
  },
  {
    "caption": "(A) Tangential eye sections through wtsX1 mutant fly eyes. In clones for the null wtsX1 allele, degeneration inside the clones is at severe stages at 14 days.",
    "ncbi_link": "wts: 43651"
  },
  {
    "caption": "(B) Tangential eye sections through sav3 clones. In sav3 after enclosure many photoreceptors are intact but after 14 days at 29°C most sav mutant photoreceptors have degenerated.",
    "ncbi_link": "sav: 252554"
  },
  {
    "caption": "(C) Histograms showing the quantification of ommatidia with the full complement of photoreceptors in hpo, wts and sav mutant clones. The progression of loss of photoreceptors is evident and statistically significant in all cases. Mutants for hpoBF33 do not survive for 14 days at 29oC and corresponding sections are shown in Supplementary Figure 12. N=195-268. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test.",
    "ncbi_link": "hpo: 37247
sav: 252554
wts: 43651"
  },
  {
    "caption": "(A) Regression analysis of the overgrowth versus the neurodegeneration observed in loss of function mutants (left) and overexpression of transgenes (right). Overgrowth quantification is shown in Supplementary Figure 14. For loss of function mutant, the neurodegeneration was quantified at 14 days in clones (as shown in Figures 4 and 5). For UAS‐overexpression transgenes neurodegeneration was quantified at 14 days when expressed with GMRGal4; UbiGal80ts. For CycD+Cdk4, these specific data are missing and have not been plotted; however, Supplementary Figure 13 shows that these mutants do not cause neurodegeneration in a different setup in which they are expressed during both development and adult life. In both cases the regression coefficient r2 is extremely low (0.21 and 0.03), indicating an absence of correlation between the two processes.",
    "ncbi_link": "UAS: "
  },
  {
    "caption": "(B) Tangential eye sections through the eyes of flies expressing with GMR-Gal4, Ubi-Gal80ts either UAS-EGFP or UAS-Yki or UAS-YkiS111A,S168A,S250A and aged 1 or 28 days. Arrows point at missing or degenerated photoreceptors. The UAS-YkiS111A,S168A,S250A is so effective that even the very low expression leaking out with this system is enough to affect development and generate mild eye roughness and overproliferation of lattice cells. Histograms showing the quantification of cell loss in eyes shown in A and also eyes from flies aged at the intermediate 14‐day stage. Mild but significant degeneration is observed for both Yki forms, with respect to the negative control; however, no statistical difference is observed between the two Yki proteins that have dramatically different effects on overgrowth. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test.",
    "ncbi_link": "EGFP: 
UAS: 
Gal4: 855828
GMR: 855828
Gal80: 854954
Yki: 37851"
  },
  {
    "caption": "Neurodegeneration by polyQ Atro partially requires dachs. Tangential eye sections through dGC13 clones (marked by the absence of yellow pigment) either in control flies or those expressing Atro75QN with the Rhodopsin1 driver and aged 28 days. Mask panels below each section exemplify clonal boundaries and PR no. for the ommatidia. Early signs of degeneration indicated by reduced complement of photoreceptors are detected specifically in the pigmented area (arrowhead). At this stage, inside d mutant clones all ommatidia are unaffected and display a wt arrangement (arrows). (B) Histograms showing the quantification of cell loss in eyes shown in (A). A statistically significant rescue is obtained both for the number of wt ommatidia (*P0.05 in two‐tailed t‐test) and for all other categories of ommatidia (χ2=44.76; P0.001 for 2 degrees of freedom).",
    "ncbi_link": "d: 33245
dachs: 33245
Atro: 46156
Rhodopsin1: 42367"
  },
  {
    "caption": "(A) EM scan of a wt (left) and ftfd mutant ommatidium (right) of a ftfd clone after 14 days. Scale bar: 1 μm. High‐magnification panels (far right, top to bottom) display autophagosomes with undigested debris, damaged mitochondria and forming phagophores (arrowheads), found in ftfd mutant cells. Scale bar: 0.2 μm for zoom‐in panels.",
    "ncbi_link": "ft: 33627"
  },
  {
    "caption": "(B) Graphs of the quantification of autophagic vesicles (AV) per photoreceptor found in EM sections of 7‐day (left)‐ and 14‐day (right)‐old ftfd clones. Significant accumulation of AV is found in mutant cells (not pigmented) with respect to genotypically wt (pigmented) cells. **P0.01 and ***P0.001 in one‐tailed t‐test. N=12 pigmented cells versus 20 non‐pigmented cells for the 7‐day graph and 13 pigmented cells versus 21 non‐pigmented cells for the 14‐day graph.",
    "ncbi_link": "ft: 33627"
  },
  {
    "caption": "(C) Confocal pictures of whole‐mount retinae of a ftfd clone aged 7 days and expressing GFP∷Atg8a ubiquitously with Tub-Gal4. Red is phalloidin marking rhabdomeres, green is GFP and the clone is marked by the absence of β‐gal staining (blue). Small GFP∷Atg8a dots accumulate specifically inside ft mutant cells (arrow).",
    "ncbi_link": "Atg8a: 32001
ft: 33627
Gal4: 855828
Tub: 40554"
  },
  {
    "caption": "(D) Confocal pictures of whole‐mount retinae of a ftfd clone aged 7 days (left) and 14 days (right). Red is phalloidin marking rhabdomeres, blue is p62 and the clone is marked by the absence of GFP staining (green). p62 starts to gather in small dots specifically inside ft mutant cells (arrow) and then accumulates massively (arrow) in the ft mutant clones as many cells degenerate.",
    "ncbi_link": "ft: 33627"
  },
  {
    "caption": "(A) EM scan of a 7‐day‐old sav3 mutant ommatidium and zoom‐in on autophagosomes containing undigested debris (arrowhead). Scale bar: 1 μm for panel on the left and 0.2 μm for zoom‐in panel on the right.",
    "ncbi_link": "sav: 252554"
  },
  {
    "caption": "(B) Graph of the quantification of autophagic vesicles (AV) per photoreceptor found in EM sections of 1‐week‐old sav3 clones. Significant accumulation of AV is found in mutant cells. ***P0.001 in one‐tailed t‐test. N=45 pigmented cells versus 42 non‐pigmented cells.",
    "ncbi_link": "sav: 252554"
  },
  {
    "caption": "D) Full-length nsp3 was expressed from a C-terminally GFP-tagged vector in HEK293T cells and treated with increasing concentrations of rac5c for 24 h. GFP is released from the C-terminus, presumably by nsp3 protease activity. Nsp3 can be detected by a SARS/SARS2 PLpro antibody (see Fig EV5E for antibody validation). Lysates were blotted for Lys48-linked polyubiquitin with a linkage specific antibody (K48). Experiments were performed in duplicate with similar results. Also see Fig EV5F, G and Source Data for uncropped blots.",
    "ncbi_link": "GFP: 
nsp3: "
  },
  {
    "caption": "B. Retrotransposition frequency (log scale) of pGAL1-Ty1his3AI bearing the indicated substitutions of conserved residues in a spt3-101 rad52∆ strain. IN1 catalytic core domain mutant D154A is defective for integration and NLS mutant (KKR628-630GGT) for nuclear import. Values are mean±SD, n=4 experiments, each performed with four independent colonies. ***p ≤ 0.001, otherwise not significant (Student t-test).",
    "ncbi_link": "IN1: 
Ty1: 
GAL1: 852308
his3: 854377
rad52: 854976
spt3: 852001"
  },
  {
    "caption": "A. Co-immunoprecipitation of ectopic IN1 using C160-HA as bait, from yeast protein extracts expressing WT or mutated IN1-Strep (K617A, S621A, or L622A) from the GAL1 promoter in the presence of galactose. Expected sizes are 160 kDa for C160-HA and 100 kDa for IN1-Strep (WT and mutants).",
    "ncbi_link": "GAL1: 852308"
  },
  {
    "caption": "B. Quantitative ChIP analysis of HA-IN1 enrichment at Pol III-transcribed genes. Immunoprecipitated DNA from yeast cells producing ectopic IN1 is expressed as a value relative to that of the input. Pol III transcribed-genes: tDNA-Ile and tDNA-Leu families (16 and 22 genes, respectively) and the unique SCR1 gene. GAL1 ORF serves as a control. Data represent means ± SD (n ≥ 3).",
    "ncbi_link": "GAL1: 852308
SCR1: 9164887"
  },
  {
    "caption": "G. Recruitment of IN1 along the SCR1 gene locus. Top. ChIP‐qPCR analysis as described for panel Fig 3B. Data represent means ± SD (n = 3). Bottom. Schematic representation of the SCR1 locus with DNA amplicon positions. TATA, A and B boxes and terminator of transcription (T) are indicated.",
    "ncbi_link": "SCR1: 9164887"
  },
  {
    "caption": "A. Detection of de novo Ty1 insertions upstream of the SUF16 and SEO1 genes by PCR using a primer in HIS3 (red triangle) and a primer in the locus of interest (blue triangle). Ty1 retrotransposition was induced in cells transformed with plasmids expressing WT or mutant (IN1 K617A, S621A and L622A) Ty1his3AI from the GAL1 promoter. Total genomic DNA was extracted from His+ cells obtained from independent cultures.",
    "ncbi_link": "Ty1: 
GAL1: 852308
HIS3: 854377
SEO1: 851230
SUF16: 850374"
  },
  {
    "caption": "B. Genome-Wide Ty1 insertion frequencies at each genomic feature are clustered in a heatmap. Score is computed in column Z-score. ORFs, all Pol II-transcribed genes except gene at subtelomeres; Pol I, one RDN37 copy; up 1kb Pol III, 1kb upstream of all Pol III transcribed genes; Subtelomeres, genomic coordinates corresponding to chromatin covered by Sir2 and Sir3, when they are co-overexpressed (Hocher et al, 2018); Random, 100 000 random Ty1 computed insertions in the genome.",
    "ncbi_link": "Ty1: 
RDN37: 9164920///9164931
Sir2: 851520
Sir3: 851163"
  },
  {
    "caption": "C. Detection of de novo Ty1 insertions upstream of RDN5 and in RDN37 genes by PCR as described for panel 5A. Four total genomic DNA preparation from panel A were randomly tested by PCR.",
    "ncbi_link": "Ty1: 
RDN37: 9164920///9164931
RDN5: 9164928///9164945"
  },
  {
    "caption": "D. Ty1 insertion profile upstream of tDNAs. Total genomic DNA extracted in (B) was prepared for Ty1 de novo integration event sequencing. Ty1 insertions are computed in a 1kb window upstream of all the 275 nuclear tDNAs (position 0 in the graph). Each position is divided by the number of insertions at this position (weight). The Smoothing curves indicate the general trend. Nucleosome center positions for the three first nucleosomes upstream of all tDNAs are from (Brogaard et al, 2012).",
    "ncbi_link": "Ty1: "
  },
  {
    "caption": "E. Ty1 insertion frequencies for each left and right subtelomere of chromosomes are clustered in a heatmap. Score is computed in row Z-score. Random, as described for panel B. High level of WT Ty1-HIS3 integration in II-L is due to the presence of the tRNA gene tF(GAA)B.",
    "ncbi_link": "Ty1: 
HIS3: 854377
tF(GAA)B: 852176"
  },
  {
    "caption": "C. Genome browser visualization of different HA-IN occupancy for chromosome V (chrV:431129..443275). Occupancy of the indicated integrase is represented in each panel. Control, as panel 3D. The region contains tH(GUG)E2, tK(CUU)E2, tV(ACC)E1, tI(AAU)E1, SNR52 and SCR1, all transcribed by Pol III.",
    "ncbi_link": "SCR1: 9164887
SNR52: 9164886
tH(GUG)E2: 856871
tI(AAU)E1: 856878
tK(CUU)E2: 856872
tV(ACC)E1: 856875"
  },
  {
    "caption": "D. Detection of Ty5, Ty5ΔTD5+bNLS or Ty1 de novo integration events at HMR and HML loci, SCR1 and upstream of all glycine tDNAs, by PCR using a primer in HIS3 and a primer in the locus of interest. Retrotransposition was induced in cells transformed with WT or mutated pGAL1-Ty5his3AI (Ty5 or Ty5ΔTD5+bNLS) and pGAL1-Ty1his3AI (Ty1). Total genomic DNA was extracted from His+ cells obtained from independent cultures. Nucleosome position (green circles) is indicated on the right of the panels (Brogaard et al, 2012).",
    "ncbi_link": "Ty1: 
Ty5: 
GAL1: 852308
HIS3: 854377
his3: 854377
SCR1: 9164887"
  },
  {
    "caption": "F.  qRT-PCR  analysis of schizonts  and oocysts  of the PbMyoA 3'dhfs parasite  line. Individual data points correspond to the mean of three technical replicates.",
    "ncbi_link": "MyoA: 55152637"
  },
  {
    "caption": "D. smFISH co-detection of k 5 mRNAs and GAPDH in subconfluent motile HUVECs. arrows indicate orientation of RNA localisation; yellow dashed lines outline cell borders; red circles highlight smFISH spots; scale bars = 20 µm",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "E. Polarisation Index (PI) of k 5 mRNAs and GAPDH in co-detected in HUVECs (n≥28 cells; **P<0.01, ***P<0.001, ****P<0.0001; Wilcoxon test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "F. k 5 mRNAs PIs plotted against respective GAPDH PIs. The slope of the coloured lines represents the average k 5 mRNA/GAPDH PI ratio; the dashed grey line represents a 1:1 ratio (n≥28 cells).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "G. Top: distribution pattern of mRNAs clustered in k 2, k 5, k 7 and GAPDH. Bottom: smFISH co-detection of exemplar k7 / k 2 mRNAs and GAPDH in subconfluent motile HUVECs. arrows indicate orientation of RNA localisation; yellow dashed lines outline cell borders; red circles highlight smFISH spots; scale bars = 20 µm",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "H. PIs of k 7 mRNAs and GAPDH co-detected in HUVECs (n≥25 cells; *P<0.05, **P<0.01, ***P<0.001; paired t test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "I. PIs of k 2 mRNAs and GAPDH co-detected in HUVECs (n≥19 cells; *P<0.05; Wilcoxon test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "E. Left: representative subconfluent motile cells co-transfected with plasmids expressing Lyn-mCherry, MCP-GFPnls and 24xMS2-RAB13 3'UTR or 24xMS2. Right: percentage of cells with MCP-GFP localised to protrusions when co-transfected with full length or deletion versions of RAB13 3'UTR (n≥3 experiments). white arrowheads indicate non-nuclear localisation of MCP-GFPnls; arrows indicate the orientation of RNA localisation; yellow dashed lines outline cell borders; scale bars = 20 µm For each k 5 mRNA 3'UTR, a diagram of the full length 3'UTR and the positions of the RNA motif is shown together with the respective RNAseq mapped reads from HUVEC protrusions; black arrowheads indicate predicted polyadenylation sites",
    "ncbi_link": "GFP: 
Lyn: 
mCherry: 
MCP: 
MS2: 
RAB13: 5872"
  },
  {
    "caption": "F. Left: representative cells co-transfected with plasmids expressing Lyn-mCherry, MCP-GFPnls and 24xMS2-k 5 3'UTRs. Right: percentage of cells with MCP-GFP localised to protrusions when co-transfected with full length or deletion versions of k 5 3'UTR (n≥3 experiments). white arrowheads indicate non-nuclear localisation of MCP-GFPnls; arrows indicate the orientation of RNA localisation; yellow dashed lines outline cell borders; scale bars = 20 µm For each k 5 mRNA 3'UTR, a diagram of the full length 3'UTR and the positions of the RNA motif is shown together with the respective RNAseq mapped reads from HUVEC protrusions; black arrowheads indicate predicted polyadenylation sites",
    "ncbi_link": "GFP: 
Lyn: 
mCherry: 
MCP: 
MS2: "
  },
  {
    "caption": "D. Wt and ∆LE HUVEC RNAseq mapped reads depicting RAB13 exon usage.",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "E. Quantification of RAB13 mRNA smFISH spot number in Wt and ∆LE HUVECs (n=3 experiments; ns: not significant; unpaired t test).",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "F. Number of RAB13 mRNA smFISH spots plotted against the respective Polarisation Index (PI) (n=29 cells; ns: not significant; linear regression).",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "H. smFISH co-detection of RAB13 and control GAPDH in Wt and ∆LE motile HUVECs cultured under subconfluent conditions. Arrows indicate orientation of RNA localisation; yellow dashed lines outline cell borders; red circles highlight smFISH spots; scale bars = 20 µm (H). Bar charts are presented as means±s.d.",
    "ncbi_link": "GAPDH: 
RAB13: 5872"
  },
  {
    "caption": "I. PI of RAB13 and GAPDH co-detected in Wt and ∆LE HUVECs (n=29 cells; P***<0.001, ns: not significant; Mann-Whitney test).",
    "ncbi_link": "GAPDH: 
RAB13: 5872"
  },
  {
    "caption": "J. RAB13 PI plotted against respective GAPDH PI. The slope of the coloured lines represents the average RAB13/GAPDH PI ratio; the dashed grey line represents a 1:1 ratio (n=29 cells).",
    "ncbi_link": "GAPDH: 
RAB13: 5872"
  },
  {
    "caption": "A. Representative time-lapse microscopy of a bEnd.3 cell co-transfected with plasmids expressing Lyn-mCherry, MCP-GFPnls and 24xMS2-RAB13 3'UTR. Arrowheads indicate filopodia",
    "ncbi_link": "GFP: 
Lyn: 
mCherry: 
MCP: 
MS2: 
RAB13: 5872"
  },
  {
    "caption": "B. Frequency of newly formed filopodia formed within 5 µm intervals relative to the nearest MCP-GFPnls particle or a randomised (ctrl) position (n=99 filopodia; **P<0.01, ns: not significant; Pearson r correlation).",
    "ncbi_link": "GFP: 
MCP: "
  },
  {
    "caption": "C. Distance of newly-formed filopodia to MCP-GFPnls or a ctrl position plotted against filopodia duration (n=99 filopodia; *P<0.05, ns: not significant; Spearman r correlation).",
    "ncbi_link": "GFP: 
MCP: "
  },
  {
    "caption": "F. Control (ctrl) and RAB13 siRNA-treated HUVECs co-cultured on fibroblast monolayers. Endothelial cells were identified with an antibody against the endothelial cell marker PECAM-1. black arrowheads indicate filopodia (F)",
    "ncbi_link": "RAB13: 5872"
  },
  {
    "caption": "A. Left: Tg(fli1ep:MCP-GFPnls) zebrafish embryo at 26 hours post fertilisation (hpf) displaying vascular-specific expression of MCP-GFPnls. Inset shows the nuclear expression of MCP-GFPnls in the intersomitic vessels (ISVs) sprouting from the dorsal aorta (DA). Middle: scheme depicts the in vivo MS2 system strategy with fli1 enhancer/promoter (fli1ep)-driven expression of reporter constructs, simultaneous translation of Lyn-mCherry reporter and binding of MCP-GFPnls to 24xMS2-rab13 3'UTR. Right: scheme illustrates ISV cells expressing Lyn-mCherry imaged in panels B-D. TC: tip cell; SC: stalk cell. Arrowheads indicate non-nuclear localisation of MCP-GFPnls; arrows indicate direction of ISV sprouting; yellow dashed lines outline ISV (A)",
    "ncbi_link": "GFP: 
Lyn: 
mCherry: 
MCP: 
MS2: 
rab13: 373105"
  },
  {
    "caption": "(B-D) Time-lapse microscopy of Tg(fli1ep:MCP-GFPnls) tip (C) and stalk (B,D) cells displaying mosaic expression of Lyn-mCherry-24xMS2-rab13 3'UTR in ISV cells. Arrowheads indicate non-nuclear localisation of MCP-GFPnls; arrows indicate direction of ISV sprouting; yellow dashed lines outline ISV cell (B-D) borders",
    "ncbi_link": "GFP: 
Lyn: 
mCherry: 
MCP: 
MS2: 
rab13: 373105"
  },
  {
    "caption": "B. Representative genotyping PCR demonstrates the band size shift in zebrafish harbouring a ∆482 rab13 3'UTR. Asterisk marks a heteroduplex formed between Wt and ∆482 rab13 3'UTR PCR amplicons.",
    "ncbi_link": "rab13: 373105"
  },
  {
    "caption": "D. RNAseq mapped reads depicting rab13 exon usage in Tg(kdrl:EGFP) rab13+/+ and rab13∆3'UTR /∆3'UTR zebrafish embryos. Coloured lines indicate SNPs.",
    "ncbi_link": "EGFP: 
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "E. qPCR analysis of rab13 mRNA levels in individual 26-28 hpf clutch-matched sibling embryos (n≥9 embryos; ns: not significant; Kruskal-Wallis test with Dunn's correction). : +/+, +/∆ and ∆/∆ represent Tg(kdrl:EGFP) rab13+/+, rab13+/∆3'UTR and rab13∆3'UTR /∆3'UTR embryos, respectively",
    "ncbi_link": "EGFP: 
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "F. smFISH detection of rab13 and kdr mRNA in cultured GFP-expressing endothelial cells extracted from 48 hpf Tg(kdrl:EGFP) rab13+/+ and rab13∆3'UTR /∆3'UTR zebrafish embryos. Arrows indicate orientation of RNA localisation; yellow dashed lines outline cell borders; red circles highlight smFISH spots; scale bars = 10 µm (F).",
    "ncbi_link": "EGFP: 
GFP: 
kdr: 554230
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "G. Polarisation Index (PI) of rab13 and kdr detected by smFISH in individual zebrafish cells (n≥8 cells; **P<0.01, ns: not significant; one-way ANOVA with Bonferroni's correction). : +/+, +/∆ and ∆/∆ represent Tg(kdrl:EGFP) rab13+/+, rab13+/∆3'UTR and rab13∆3'UTR /∆3'UTR embryos, respectively",
    "ncbi_link": "EGFP: 
kdr: 554230
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "H. rab13 PI plotted against respective kdr PI. The slope of the coloured lines represents the average rab13/kdr PI ratio; the dashed grey line represents a 1:1 ratio (n≥8 cells). : +/+, +/∆ and ∆/∆ represent Tg(kdrl:EGFP) rab13+/+, rab13+/∆3'UTR and rab13∆3'UTR /∆3'UTR embryos, respectively",
    "ncbi_link": "EGFP: 
kdr: 554230
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "A. Time-lapse confocal microscopy of representative Tg(kdrl:EGFP) rab13+/+ and rab13∆3'UTR /∆3'UTR embryos. DLAV: dorsal longitudinal anastomotic vessel; HM: horizontal myoseptum. T0= 25 hpf; arrowheads indicate extra branches emerging from the main ISVs at the HM position; scale bars = 50 µm (A).",
    "ncbi_link": "EGFP: 
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "B. Frequency of ISV ectopic branching occurring at the HM (n=4 experiments; *P<0.05; one-way ANOVA with Bonferroni's correction). +/+, +/∆ and ∆/∆ represent Tg(kdrl:EGFP) rab13+/+, rab13+/∆3'UTR and rab13∆3'UTR /∆3'UTR embryos, respectively (B).",
    "ncbi_link": "EGFP: 
kdrl: 796537
rab13: 373105"
  },
  {
    "caption": "qPCR quantification of overall PAX6 gene expression during human forebrain and retinal differentiation (n=3 biological replicates for each group). qPCR quantification of PAX6A&B isoform expression during human forebrain and retinal differentiation (n=3 biological replicates for each group). qPCR of PAX6D isoform expression during human forebrain and retinal differentiation (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6: 5080
PAX6A: 5080
PAX6D: 5080"
  },
  {
    "caption": "qPCR quantification of PAX6 expression in Wildtype and PAX6 KO during retinal differentiation (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6: 5080"
  },
  {
    "caption": "Western blot detection of PAX6 in Wildtype and PAX6 KO cells at day 20 of retinal differentiation.",
    "ncbi_link": "PAX6: 5080"
  },
  {
    "caption": "Immunostaining of PAX6 in Wildtype and PAX6 KO cells. C'-PAX6 antibody detects PAX6A, B and D. N'-PAX6 antibody detects PAX6 A and B but not D. Scale bars: 50 µm.",
    "ncbi_link": "PAX6: 5080"
  },
  {
    "caption": "qPCR quantification of retinal related genes in Wildtype and PAX6 KO cells. Samples are collected at day 6, 10, 14 and 19 after the start of differentiation.",
    "ncbi_link": "PAX6: 5080"
  },
  {
    "caption": "qPCR verification of PAX6D KO efficiency. PAX6A&B and PAX6D isoforms were also evaluated by qPCR with isoform specific primers (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6A: 5080
PAX6D: 5080"
  },
  {
    "caption": "Western blot detection of PAX6 isoforms in wildtype and PAX6D KO cells.",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "qPCR quantification of retinal gene VSX2 in PAX6D KO cells (n=3 biological replicates for each group).   qPCR quantification of retinal gene SIX6 in PAX6D KO cells (n=3 biological replicates for each group).   ",
    "ncbi_link": "PAX6D: 5080
SIX6: 4990
VSX2: 338917"
  },
  {
    "caption": "Immunostaining of VSX2 in wildtype and PAX6D KO cells. Scale bars:100 µm. Samples were from day 30 differentiating retinal cells.",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "Flow cytometry analysis of day 7 cell cultures under retinal differentiation from wildtype, PAX6 KO and PAX6D KO cell lines. Flow cytometry analysis of day 20 cell cultures under retinal differentiation from wildtype, PAX6 KO and PAX6D KO cell lines.",
    "ncbi_link": "PAX6: 5080
PAX6D: 5080"
  },
  {
    "caption": "qPCR quantification of SOX1 in wildtype, PAX6 KO and PAX6D KO cell at day 20 of retinal differentiation (n=3 biological replicates for each sample).",
    "ncbi_link": "PAX6: 5080
PAX6D: 5080
SOX1: 6656"
  },
  {
    "caption": "qPCR quantification of PAX6A and PAX6D gene expression under the treatment of DOX (n=3 biological replicates for each sample).",
    "ncbi_link": "PAX6A: 5080
PAX6D: 5080"
  },
  {
    "caption": "qPCR quantification of SOX1 gene expression in the PAX6A TetOn and PAX6D TetOn cells (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6A: 5080
PAX6D: 5080
SOX1: 6656"
  },
  {
    "caption": "qPCR quantification of retinal marker expression in PAX6D TetOn cells w/o DOX treatment (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "Verification of PAX6D target genes using PAX6D TetOn cells. Two sets of genes (retinal and non-retinal neural genes) are directly regulated by PAX6D in opposite directions (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "qPCR quantification of WNT8B in PAX6D KO cells at multiple time points during retinal differentiation (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080
WNT8B: 7479"
  },
  {
    "caption": "qPCR quantification of retinal gene expression in PAX6D KO cells treated with WNT antagonist IWR1 to rescue the retinal differentiation (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "Western blot of WNT8B and ACTIN in PAX6D KO cells with treatment of untreat, control shRNA lentivirus, WNT8B shRNA lentivirus.",
    "ncbi_link": "PAX6D: 5080
WNT8B: 7479"
  },
  {
    "caption": "qPCR quantification of retinal marker expression in PAX6D KO cells treated with control shRNA lentivirus and WNT8B shRNA lentivirus (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080
WNT8B: 7479"
  },
  {
    "caption": "qPCR quantification of retinal gene expression in PAX6D TetOn cells when PAX6D was induced by DOX in the presence of WNT agonist CHIR99021 (n=3 biological replicates for each group).",
    "ncbi_link": "PAX6D: 5080"
  },
  {
    "caption": "C. Proteins from whole cell extracts and culture supernatants of PAKΔretS, the derivative tssA1 mutant (ΔA1) (both carrying the pBBR plasmid) and the complemented ΔA1 mutant carrying pBBR-tssA1 (ΔA1+A1) were analysed by Western blot. Polyclonal antibodies directed against TssA1 (A1), Hcp1, VgrG1a and Tse3 were used. The anti-VgrG1a antibody detects VgrG1a, VgrG1b and VgrG1c, as indicated on the left. Cytoplasmic RNA polymerase (RNAP) was monitored using monoclonal antibody directed against its β-subunit.",
    "ncbi_link": "tssA1: 
retS: 877881"
  },
  {
    "caption": "A. BTH experiments showing that TssA1 is able to self-interact in vivo. A graphical representation of β-galactosidase activity from co-transformants of E. coli DHM1 cells producing TssA1 (A1) fused to the adenylate cyclase T25 or adenylate cyclase T18 subunits is shown. The values shown on the y axis correspond to the activity in Miller units. In each case, average activity from two independent experiments is shown and error bars indicate the standard deviation (S.D.). Experiments were carried out in quadruplicate.",
    "ncbi_link": "β-galactosidase: "
  },
  {
    "caption": "D. BTH experiment showing interaction between TssA1 (A1) and Hcp1. A graphical representation of β-galactosidase activity from E. coli DHM1 cells producing the indicated proteins fused to the adenylate cyclase T25 or adenylate cyclase T18 subunits is shown. The values shown on the y axis correspond to the activity in Miller units. In each case, average activity from two independent experiments is shown and error bars indicate the standard deviation (S.D.). Experiments were carried out in triplicate.",
    "ncbi_link": "β-galactosidase: "
  },
  {
    "caption": "BTH screen for interactions between TssA1 and T6SS components of interest. A graphical representation (bottom) of β-galactosidase activity from E. coli DHM1 cells producing the indicated proteins fused to the adenylate cyclase T25 or adenylate cyclase T18 subunits and images of corresponding spots on X-gal LB agar plates (top) are shown. The combination of T25/T18 fusion proteins are indicated as 25 or 18 followed by the name of the fused T6SS protein. T6SS proteins are abbreviated as follows: A1=TssA1, E1=TssE1, F1=TssF1, G1=TssG1 and K1=TssK1. The values shown on the y axis correspond to the activity in Miller units. In each case, average activity from two independent experiments is shown and error bars indicate the standard deviation (S.D.). Experiments were carried out in triplicate.",
    "ncbi_link": "β-galactosidase: "
  },
  {
    "caption": "(a) Nuclear localization of HLH-30 was visualized by fluorescence microscopy in day 1 adult wild-type (WT) (upper panel) and glp-1(e2141) (lower panel) animals expressing HLH-30::GFP raised at the non-permissive temperature (25°C). Inserts show enlarged intestinal cells. Graph shows percentage of animals with HLH-30 in the nuclei of intestinal cells (four biological replicates, ~50 animals each, mean±s.d., **P0.01, Student's t-test). Magnification × 100; scale bar, 100 μm.",
    "ncbi_link": "glp-1: 176286"
  },
  {
    "caption": "(b) Expression of hlh-30 and putative autophagy-related and lysosomal target genes was measured by quantitative PCR (qPCR) in day 1 adult WT and glp-1(e2141) animals raised at 25°C (mean±s.d. of three biological replicates, *P0.05, **P0.01, Student's t-test).",
    "ncbi_link": "hlh-30: 177157
glp-1: 176286"
  },
  {
    "caption": "(c) Expression of hlh-30 and putative autophagy-related and lysosomal target genes was measured by qPCR in day 1 adult glp-1(e2141) and glp-1(e2141); hlh-30(tm1978) animals raised at 25°C (mean±s.d. of three biological replicates, *P0.05, **P0.01, Student's t-test). ctsa* is a cathepsin A orthologue (cosmid C08H9.1 (ref. 30)). See Supplementary Fig. 1 for qPCR analyses of hlh-30(tm1978) (control for c) and WT and glp-1(e2141) animals fed bacteria expressing hlh-30 dsRNA.",
    "ncbi_link": "ctsa: 5476
glp-1: 176286
hlh-30: 177157"
  },
  {
    "caption": "(d,e) GFP::LGG-1 punctae were quantified in (d) hypodermal seam cells or (e) proximal intestinal cells of L3 larvae of WT and glp-1(e2141) animals. Animals were fed bacteria expressing control or hlh-30 dsRNA for two generations at 20 °C. Eggs were then transferred to plates seeded with the appropriate dsRNA-expressing bacteria at 25 °C and analysed at the L3 larval stage (mean±s.e.m. of ~300 seam cells and ~25 intestines, **P0.01, Student's t-test).",
    "ncbi_link": "glp-1: 176286
hlh-30: 177157"
  },
  {
    "caption": "(f,g) glp-1(e2141) animals expressing (f) LMP-1::GFP or (g) SQST-1::GFP were raised at the non-permissive temperature (25°C) and fed bacteria expressing control or hlh-30 dsRNA from hatching. Micrographs of the posterior intestine were taken on day 1 of adulthood, and LMP-1::GFP fluorescence (mean±s.d. of ~10 animals, **P0.01, Student's t-test) and SQST-1::GFP foci (mean±s.d. of ~30 animals, **P0.01, Student's t-test) were quantified. Experiments were performed at least three times with similar results. See Supplementary Fig. S2a,c for images of whole animals and Supplementary Fig. S2b,d for replicates. Magnification, × 200; scale bar, 100 μm.",
    "ncbi_link": "glp-1: 176286
hlh-30: 177157"
  },
  {
    "caption": "(a) Nuclear localization of HLH-30 was quantified in day 1 adult animals expressing HLH-30::GFP. Animals were fed bacteria expressing control or tor dsRNA from hatching and raised at 20 °C (three biological replicates, ~50 animals each, mean±s.d., **P0.01, Student's t-test).",
    "ncbi_link": "tor: 172167"
  },
  {
    "caption": "b,c) Expression of putative autophagy-related and lysosomal target genes was measured by quantitative PCR in day 1 (b) WT (N2) and (c) hlh-30(tm1978) animals fed bacteria expressing control or tor dsRNA from hatching (20 °C). Data are mean±s.d. of biological triplicates. *P0.05, **P0.01; Student's t-test. csta* is a cathepsin A orthologue (cosmid C08H9.1 (ref. 30)).",
    "ncbi_link": "hlh-30: 177157
tor: 172167"
  },
  {
    "caption": "(d) Lifespan analysis of WT animals and hlh-30(tm1978) mutants fed bacteria expressing control or tor dsRNA from day 1 of adulthood was carried out at 20 °C. See Supplementary Table S3 for details of lifespan analyses and replicate experiments.",
    "ncbi_link": "hlh-30: 177157
tor: 172167"
  },
  {
    "caption": "Lifespan analyses of (a) WT (N2) and (b) germline-less glp-1(e2141) animals raised at the non-permissive temperature (25 °C) and fed bacteria expressing control or hlh-30 dsRNA from day 1 of adulthood were carried out at 20 °C. Lifespan analyses of (c) dietary-restricted eat-2(ad1116) mutants, (d) insulin/IGF-1 receptor daf-2(e1370) mutants, (e) mitochondrial respiration clk-1(e2519) mutants and (f) mRNA translation rsks-1(sv31) mutants, fed bacteria expressing control or hlh-30 dsRNA from day 1 of adulthood (c,d,f) or larval L4 stage (e), were carried out at 20 °C. See Supplementary Table S2 for details of lifespan analyses including at least three independent experiments.",
    "ncbi_link": "rsks-1: 176554
eat-2: 175072
daf-2: 175410
clk-1: 175729
glp-1: 176286
hlh-30: 177157"
  },
  {
    "caption": "(a) Nuclear localization of HLH-30 was quantified in day 1 adult WT, eat-2, daf-2, clk-1 and rsks-1 mutants (mean±s.d. of four biological replicates, ~50 animals each, **P0.01, analysis of variance).",
    "ncbi_link": "clk-1: 175729
daf-2: 175410
eat-2: 175072
rsks-1: 176554"
  },
  {
    "caption": "(b) Expression of hlh-30 was measured by quantitative PCR (qPCR) in day 1 adult WT (N2), eat-2(ad1116) (dietary restriction, DR), daf-2(e1370) (insulin/IGF-1 signaling), clk-1(e2519) (mitochondrial respiration) and rsks-1(sv31) (mRNA translation) animals (mean±s.d. of three biological replicates, *P0.05, Student's t-test).",
    "ncbi_link": "clk-1: 175729
daf-2: 175410
eat-2: 175072
hlh-30: 177157
rsks-1: 176554"
  },
  {
    "caption": "(c) Lifespan analysis of WT and transgenic animals overexpressing HLH-30::GFP, and raised and maintained on OP50 was carried out at 20 °C. See Supplementary Table S7 for details of lifespan analyses and replicate experiments.",
    "ncbi_link": "HLH-30: 177157"
  },
  {
    "caption": "(d) GFP::LGG-1 punctae were quantified in hypodermal seam cells of WT animals or animals overexpressing HLH-30 (n>300, ±s.e.m., **P0.01, Student's t-test). The increase in GFP::LGG-1 punctae observed in animals overexpressing HLH-30 could be reversed by atg-18 RNAi treatment (data not shown).",
    "ncbi_link": "HLH-30: 177157"
  },
  {
    "caption": "(e) TFEB expression was measured by qPCR in the livers of 4.5-month-old female (F) and male (M) mice fed AL or subjected to DR for 5.5 weeks starting at 3 months of age (mean±s.e.m. of ~20 mice per group, *P0.05, Student's t-test).",
    "ncbi_link": "TFEB: 21425"
  },
  {
    "caption": "B. Cycloheximide chase analysis on N2a cells expressing Sig1R-FLAG. Quantitative data of immunoblotting for the levels of Sig1R-FLAGprotein and its variants during the cyclohexamide chase were plotted as mean ± SEM of three independent experiments (upper panel). Representative immunoblots for the levels of Sig1R-FLAGproteins were shown (lower panel). **: p < 0.01, *: p = 0.0216 in E102Q vs. wild-type (WT); ##: p < 0.01, #: p < 0.05 in L95fs vs. WT. A one-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "Sig1R: 10280"
  },
  {
    "caption": "C. N2a cells transfected with Sig1R-FLAG variants were incubated with MG-132 (10 µM) or the combination of E64d and pepstatin A (5 µg/mL each) (E64d/PepA) for 8 h. The relative mean levels of Sig1R-FLAG variants determined by immunoblotting from three independent experiments were plotted as mean ± SEM (upper panel). The representative immunoblots were shown (lower panel). *: p < 0.05 vs. no inhibitor control. A one-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "Sig1R: 10280"
  },
  {
    "caption": "E and F. Subcellular localization of inositol 1,4,5-triphosphate receptor type 1 (IP3R1) and type 3 (IP3R3) in N2a cells stably expressing human IP3R3 (N2a-IP3R3 cells, E). IP3R1 and IP3R3 in the isolated fractions were identified by immunoblotting with the specific antibodies as indicated. Proper fractionation of these samples was confirmed by the fraction specific markers as indicated.",
    "ncbi_link": "IP3R3: 3710"
  },
  {
    "caption": "G. Interaction of IP3R3 with wild-type Sig1R or E102Q ALS-linked Sig1R mutant. Sig1R-FLAG variants were transfected in N2a-IP3R3 cells, and IP3R3 was co-immunoprecipitated using an anti-FLAG antibody and identified by immunoblotting with the specific antibodies as indicated.",
    "ncbi_link": "IP3R3: 3710
Sig1R: 10280"
  },
  {
    "caption": "H. Suppression of Sig1R by siRNA. Lysates of N2a cells transfected with control siRNA (siCtrl) or siRNA against Sig1R (siSig1R) for 24 h were blotted. Similar results were obtained from three independent experiments. Paired t-test was used for statistical analysis.",
    "ncbi_link": "Sig1R: 18391"
  },
  {
    "caption": "I and J. Cytoplasmic calcium (Ca2+) flux in N2a or human IP3R3 stably expressing N2a (N2a-IP3R3) cells. siCtrl or siSig1R was transfected to N2a or N2a-IP3R3 cells, then cytoplasmicCa2+ flux were determined with fluo-4 and Case12-mito, respectively. The fluorescent intensity was normalized to the intensity in resting state at 0 s, and plotted as mean ± SD.",
    "ncbi_link": "IP3R3: 3710
Sig1R: 18391"
  },
  {
    "caption": "I and J. mitochondrial (J) calcium (Ca2+) flux in N2a or human IP3R3 stably expressing N2a (N2a-IP3R3) cells. siCtrl or siSig1R was transfected to N2a or N2a-IP3R3 cells, then mitochondrial Ca2+ flux were determined with fluo-4 and Case12-mito, respectively. The fluorescent intensity was normalized to the intensity in resting state at 0 s, and plotted as mean ± SD.",
    "ncbi_link": "IP3R3: 3710
Sig1R: 18391"
  },
  {
    "caption": "K and L. Cytoplasmic (K) or mitochondrial (L) Ca2+ flux in N2a-IP3R3 cells. siCtrl or siSig1R was transfected with or without the Sig1R-FLAG variants. The data are obtained and plotted as described above. n = 10 each. **: p < 0.01, *: p < 0.05 (I-L). Two-way ANOVA with subsequent post hoc Tukey's test (I-J).",
    "ncbi_link": "IP3R3: 3710
Sig1R: 10280"
  },
  {
    "caption": "A. The levels of Sig1R in the lumbar spinal cord (LSC) or brain of Sig1R−/−, Sig1R+/−, or Sig1R+/+ mice at 5 months old. Representative immunoblots obtained from three independent experiments are shown. Asterisk denotes non-specific bands.",
    "ncbi_link": "Sig1R: 18391"
  },
  {
    "caption": "B and C. Sig1R-deficient SOD1G85Rmice (SOD1G85R/Sig1R−/−) exhibited accelerated onset of the disease (B) and shortened survival time (C) compared to SOD1G85Rmice with one or two copies of Sig1R (SOD1G85R/Sig1R+/−, SOD1G85R/Sig1R+/+). Open circles indicate Sig1R knockout mice (Sig1R−/−) that never developed motor neuron disease but that were sacrificed at 396 days of age (n = 8). Mean onset or survival times of mice with ±SD are shown on the top of Kaplan-Meyer curves. **: p < 0.01, *: p < 0.05, log-rank test. n = 14 (SOD1G85R/Sig1R+/+), 29 (SOD1G85R/Sig1R+/−), 17 (SOD1G85R/Sig1R−/−).",
    "ncbi_link": "Sig1R: 18391
SOD1: 20655"
  },
  {
    "caption": "D and E. Body weights were lost earlier both in male (D) and female (E) of SOD1G85R/ Sig1R−/−mice. Data are shown as mean ± SD. *: p < 0.05 in SOD1G85R/Sig1R+/+ vs. SOD1G85R/Sig1R−/−, †: p < 0.05 in SOD1G85R/Sig1R+/− vs. SOD1G85R/Sig1R−/−. n = 8 (SOD1G85R/Sig1R+/+), 13 (SOD1G85R/Sig1R+/−), 8 (SOD1G85R/Sig1R−/−) in male (D), and n = 6 (SOD1G85R/Sig1R+/+), 16 (SOD1G85R/Sig1R+/−), 9 (SOD1G85R/Sig1R−/−) in female (E). The used animals were the same in the panels B and C. The animals used in the panels D and E were the same in the panels B and C. *: p < 0.05 in SOD1G85R/Sig1R+/+ vs. SOD1G85R/Sig1R−/−, †: p < 0.05 in SOD1G85R/Sig1R+/− vs. SOD1G85R/Sig1R−/−. Two-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "Sig1R: 18391
SOD1: 20655"
  },
  {
    "caption": "F. Decreased performance on the rotarod test was observed in SOD1G85R/ Sig1R−/−mice. The test was performed at 0-30 rpm with 0.1 rpm/s acceleration every week. Data are shown as mean ± SD. **: p < 0.0001 in SOD1G85R/Sig1R+/+ vs. SOD1G85R/Sig1R−/−, † †: p < 0.0001 in SOD1G85R/Sig1R+/− vs. SOD1G85R/Sig1R−/−. The used animals were the same in the panels B-E. Two-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "Sig1R: 18391
SOD1: 20655"
  },
  {
    "caption": "G and H. Motor function of WT (Sig1R+/+) and Sig1R knockout (Sig1R−/−) mice at 5 or 12 months old was evaluated by the rotarod test (0-30 rpm, accelerated at 0.1 rpm/s). Average time on the rotating rod was plotted. Error bars denote SD. Unpaired t-tests.",
    "ncbi_link": "Sig1R: 18391"
  },
  {
    "caption": "A and B. N2a cells expressing SOD1WT, SOD1G85R or SOD1G93A (A), or spinal cords of WT or mutant SOD1 transgenic mice at end-stage (B) were fractionated as described in Materials and methods section (Cyto: cytoplasm, P1: nuclei and debris, Mito: mitochondria, MAM: mitochondria-associate membrane, P3: microsomal fraction). Proper fractionation was confirmed by the fraction specific markers as indicated, and also shown in Fig EV1 A-E. An asterisk denotes non-specific bands.",
    "ncbi_link": "SOD1: 6647
SOD1: 20655"
  },
  {
    "caption": "C. Tissue and cell-type specific accumulation of mutant SOD1 at the MAM. Brain, liver, or primary astrocytes from SOD1G93Amice were fractionated and blotted as in Figures 4A and B (Upper panel). Quantification of SOD1 proteins at the MAM relative to ones in the cytoplasm was performed from immunoblotting data with an anti-human SOD1 antibody in (B) and the top panel of (C), and the data are plotted as mean ± SEM from three independent experiments (Lower panel). **: p < 0.01 vs. SOD1WTspinal cord. A one-way ANOVA with subsequent post hoc Tukey's test.Proper fractionation of these samples was confirmed in Fig EV 1F-H.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "D. Mutant SOD1 prevented association of ER with mitochondria. Isolated ER (P3: microsomal fraction) and mitochondria of N2a cells expressing wild-type (WT) or G85R (85) SOD1 for 48 h were mixed and incubated. Mitochondrial pellets after centrifugation were analyzed by immunoblotting using anti-PDI (ER marker) and anti-VDAC (mitochondrial marker), respectively. All these results were confirmed by three independent experiments.",
    "ncbi_link": "SOD1: 20655"
  },
  {
    "caption": "A and B. Time course analyses of mutant SOD1 levels at the MAM in SOD1G93Amousespinal cords (A) and brains (B). Immunoblots show levels of mutant SOD1 protein in the indicated fractions at various time points (left panels). Quantitative data at the right were plotted as mean ± SEM of three independent experiments. Arrows indicate a rapid reduction in SOD1 level at the MAM just following the onset of disease.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "C and D. Time course analyses of mutant SOD1 accumulation at the MAM in SOD1G85R (C) and SOD1G37R (D) mousespinal cords. Quantitative data from three independent experiments were plotted (bottom). The arrows in the bottom panel are the same as in A and B.",
    "ncbi_link": "SOD1: 20655
SOD1: 6647"
  },
  {
    "caption": "E. Time course analyses of MAM-specific proteins at MAM and in the whole lysates of SOD1G93Amousespinal cords.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "A-I. Immunofluorescence staining of spinal cords and brains from non-transgenic (Non-Tg), SOD1 transgenic, or Sig1R−/−mice. Transverse sections of mousespinal cords (A, D-I) or sagittal sections of mouse brains (B, C) were stained using anti-Sig1R (white), βIII-tubulin (red) and IP3R3 (green) antibodies. Note that Sig1R and IP3R3 are co-localized in the motor neurons of the anterior horn (A) and the hypoglossal nucleus (B), and IP3R3 was not expressed in hippocampal neurons (C). Mutant SOD1 induced aggregation of Sig1R and mislocalization of IP3R3 in anterior horn neurons (D-G), while their abnormalities were not observed in SOD1WTmotor neurons (H). Mislocalization of IP3R3 was also observed in Sig1R−/−mouse spinal cords (I). Scale bars: 50 µm.",
    "ncbi_link": "Sig1R: 18391
SOD1: 20655
SOD1: 6647"
  },
  {
    "caption": "J and K. Representative electron micrographs of the MAM (J) (double-headed arrows) in motor neurons of 12 months-old Non-Tg, SOD1G85R or Sig1R−/−mice. Note that ER-mitochondria contacted areas were reduced in both SOD1G85R or Sig1R−/−mice. Quantification of the mitochondria surface associated to ER was calculated in K. For quantification, 13-19 motor neurons and 224-316 mitochondria with MAM in each animal (n = 2) were analyzed. Data are expressed as mean ± SEM. Double asterisk means p < 0.0001 vs Non-Tg. A one-way ANOVA with subsequent post hoc Tukey's test. Scale bars: 300 nm.",
    "ncbi_link": "Sig1R: 18391
SOD1: 20655"
  },
  {
    "caption": "L. The levels for IP3R3 and calreticulin were decreased in the MAM fractions of Sig1R−/−mouse brains. MAM fractions and whole tissue lysates of Sig1R+/+ or Sig1R−/−mouse brains were immunoblotted. Representative blots from three independent experiments are shown.",
    "ncbi_link": "Sig1R: 18391"
  },
  {
    "caption": "A. N2a cells were transfected with WT or mutant SOD1 in the presence or absence of IP3R3. Plotted viability of the cells measured by a neurotoxicity assay revealed that IP3R3 is involved in cell vulnerability against mutant SOD1. Data are expressed as mean ± SEM from three independent experiments, triplicated in each experiment. **: p < 0.01, *: p < 0.05.",
    "ncbi_link": "IP3R3: 3710
SOD1: 6647
SOD1: 20655"
  },
  {
    "caption": "B-G. Calpain activity (B-D) were measured in N2a-IP3R3 cells expressing Sig1R-FLAG (B and E), SOD1 (C and F), or both (D and G). Mean ± SEM from three independent experiments is plotted. *: p < 0.05.",
    "ncbi_link": "IP3R3: 3710
Sig1R: 10280
SOD1: 20655"
  },
  {
    "caption": "B-G. intracellular ATP levels (E-G) were measured in N2a-IP3R3 cells expressing Sig1R-FLAG (B and E), SOD1 (C and F), or both (D and G). Mean ± SEM from three independent experiments is plotted. *: p < 0.05.",
    "ncbi_link": "IP3R3: 3710
Sig1R: 10280
SOD1: 20655"
  },
  {
    "caption": "A and B. Cytoplasmic (A) or mitochondrial (B) Ca2+ flux was measured in N2a-IP3R3 cells treated with PRE-084 (5 µM) or NE-100 (5 µM) for 1 h prior to fluorescent imaging. Cytoplasmic and mitochondrialCa2+ flux were detected by fluo-4 and Case12-mito, respectively. The fluorescent intensity was normalized by the resting state at 0 s, and plotted as mean ± SD. n = 10 each. **: p < 0.01, *: p < 0.05. Two-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "IP3R3: 3710"
  },
  {
    "caption": "C and D. Calpain activity were measured in N2a-IP3R3 cells treated with PRE-084 (5 µM) or NE-100 (5 µM) for 24 h. Data are plotted as mean ± SEM from three independent experiments. *: p < 0.05 vs. mock control. A one-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "IP3R3: 3710"
  },
  {
    "caption": "C and D. intracellular ATP levels were measured in N2a-IP3R3 cells treated with PRE-084 (5 µM) or NE-100 (5 µM) for 24 h. Data are plotted as mean ± SEM from three independent experiments. *: p < 0.05 vs. mock control. A one-way ANOVA with subsequent post hoc Tukey's test.",
    "ncbi_link": "IP3R3: 3710"
  },
  {
    "caption": "E and F. SOD1G93Amice were intraperitoneally administered with saline or PRE-084 (0.25 mg/kg, 3 times per week) from postnatal day 35 to 95. Lumbar spinal cord sections were stained by using anti-Sig1R (white), IP3R3 (green), and βIII-tubulin (red) at 95 days old. Arrowheads indicate the neurons with normal distribution of Sig1R and IP3R3. Scale bars: 50 µm.",
    "ncbi_link": "SOD1: 6647"
  },
  {
    "caption": "B. Cell lines generated from WT, null, and mutant p53 esophagi were assessed by Western blot analysis for p53 protein expression. Relative intensity densitometry of Rab11-FIP1 results are shown at the bottom.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "C. Organoids generated from WT, mutant, and null p53 cell lines. Scale bar: 100μm. D. Quantification of the portion of organoids exhibiting a solid, intermediate or stratified morphology (> 37 organoids from 2-3 cell lines per group). ",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "E-G. Cells were subcutaneously injected in the lower flanks of nude mice (n= 4 flanks/cell line. WT p53 2 cell lines, Mutant p53-3 cell lines, p53 null-3 cell lines). E. The number of tumors formed in each group was quantified. F. Tumor growth was measured at the indicated time points post-implantation. Graph represents total tumor size per group. G. Average tumor weight following dissection (n=2 biological replicates for WT p53 cell lines, n=3 biological replicates for mutant p53 cell lines, n=3 biological replicates for p53 null cell lines, n=4 technical replicates injected per cell line, calculated as average tumor weight per cell line). Error bars represent ±S.E.M. *p=0.02 Mutant p53 vs WT p53, *p=0.02 Mutant p53 vs Null p53 (One-way Anova).",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "B. Relative fold change in expression level of endocytic recycling genes in invasive vs. non-invasive cells, and in mutant vs. WT p53 cells based on microarray and RNA-seq analysis, respectively.",
    "ncbi_link": "p53: 22059"
  },
  {
    "caption": "C. qPCR analysis of recycling-related gene expression in mutant p53 relative to WT p53 cells (red and black bars, respectively). Graphs represent mean ± SEM (n=3 biological replicates for Rab11-FIP1, Rab25, Myo5b and Clic3; n=2 biological replicates for Rab5). Rab11-FIP1 *p=0.0109, Rab25 **p=0.0021, Myo5b ***p=0.0001, Clic3 **p=0.0051, Rab5 no significant differences (n.s.). (Unpaired t-test).",
    "ncbi_link": "Clic3: 69454
Myo5b: 17919
Rab25: 53868
Rab5: 54189
p53: 22059"
  },
  {
    "caption": "A. Western blot confirming knockdown of Rab11-FIP1 by shRNAs. Relative intensity by densitometry of Rab11-FIP1 results are shown at the bottom.",
    "ncbi_link": "Rab11-FIP1: 75767"
  },
  {
    "caption": "3D organoids were generated from WT and mutant p53 cells expressing non-targeting control (NT) or Rab11-FIP1 shRNAs (sh1 and sh2). B. Diameter of organoids (n= 80-130 organoids). Bar graph represents mean diameter ± SEM. ****p<0.0001 WT or mutant p53 non-targeting control vs Rab11-FIP1 shRNA1, ***p=0.0006 WT non-targeting control vs Rab11-FIP1 shRNA2, ****p<0.0001 mutant p53 non-targeting control vs Rab11-FIP1 shRNA2 (One-way Anova). ****p<0.0001 WT vs mutant p53 non-targeting control (Unpaired t-test).",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "3D organoids were generated from WT and mutant p53 cells expressing non-targeting control (NT) or Rab11-FIP1 shRNAs (sh1 and sh2). C. Percent of WT p53 (top panel) and mutant (bottom panel) organoids exhibiting a solid, intermediate, or stratified morphology (n>50 organoids generated from three different cell passages quantified). Bar graph represents mean diameter ± SEM. n.s. WT p53 non-targeting control vs Rab11-FIP1 shRNAs, *p=0.046 mutant p53 non-targeting control vs Rab11-FIP1 shRNA1, ***p=0.0002 mutant p53 non-targeting control vs Rab11-FIP1 shRNA2 (One-way Anova).",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "3D organoids were generated from WT and mutant p53 cells expressing non-targeting control (NT) or Rab11-FIP1 shRNAs (sh1 and sh2). D. Percent of WT p53 and mutant organoids exhibiting a basaloid-like morphology (n>50 organoids generated from three different cell passages quantified). Bar graph represents mean diameter ± SEM. n.s. WT p53 non-targeting control vs Rab11-FIP1 shRNAs, *p=0.046 mutant p53 non-targeting control vs Rab11-FIP1 shRNA1, ***p=0.0002 mutant p53 non-targeting control vs Rab11-FIP1 shRNA2 (One-way Anova).",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "3D organoids were generated from WT and mutant p53 cells expressing non-targeting control (NT) or Rab11-FIP1 shRNAs (sh1 and sh2). E. WT p53 organoids stained for H&E (left), Rab11-FIP1 (middle), and the basal cell marker p63 (right) by IHC. 40X. Scale bar = 100 μm. F. Mutant p53 organoids stained for H&E (left), Rab11-FIP1 (middle), and the basal cell marker p63 (right) by IHC. 40X. Scale bar = 100 μm.",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "A. EPC2-hTERT-EGFR-p53R175H cells grown in OTC stained for RCP. Arrow indicates invasive region. (scale bar = 100 μm).",
    "ncbi_link": "EGFR: 1956
hTERT: 7015
p53: 7157"
  },
  {
    "caption": "B. Transwell Boyden Chamber invasion assay of WT and mutant p53 cells expressing non-targeting control (NT) and Rab11-FIP1 shRNAs (sh1 and sh2) (n=9 technical replicates from 3 different passages). Error bars represent ±S.E.M. n.s. WT p53 NT vs sh1, ***p=0.0005 WT p53 NT vs sh2, n.s. Mutant p53 NT vs sh1,** p=0.0026 Mutant p53 NT vs sh2, (One-way Anova) *p=0.0173 WT p53 NT vs Mutant p53 NT, (unpaired t-test).",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "C-D. WT and mutant p53 cells expressing non-target control and Rab11-FIP1 shRNAs were grown in OTC. C. H&E staining of OTC with WT p53 (top) and mutant p53 (bottom) with invasive regions. Scale bar = 50 μm. D. Graph shows relative invasive area from OTC of WT p53 non-target control and Rab11-FIP1 shRNAs. n=5 technical replicates in WT p53 NT, n=6 technical replicates in WT p53 sh1, n=6 technical replicates in WT p53 sh2. Error bars represent ±S.E.M. **** p<0.0001 WT p53 NT vs sh1, n.s. WT p53 NT vs sh2(One-way Anova).",
    "ncbi_link": "Rab11-FIP1: 75767
p53: 22059"
  },
  {
    "caption": "A. Immunofluorescent staining for Rab11-FIP1 in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm B. Immunofluorescent staining for f-actin in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm C. Immunofluorescent staining for E-cadherin, in TE1 and TE2 ESCC cell lines expressing a non-targeting control shRNA or shRNA against Rab11-FIP1. Scale bar= 50 μm ",
    "ncbi_link": "Rab11-FIP1: 75767"
  },
  {
    "caption": "D. qPCR analysis of epithelial and mesenchymal gene expression in TE1 (left) and TE2 (right) cells expressing Rab11-FIP1 shRNA relative to control cells (dotted line). Graph error bars represent mean SEM (n=3 technical replicates from three different cell passages). n.s. TE2 SNAI2, *p<0.05,(Unpaired t-test).",
    "ncbi_link": "Rab11-FIP1: 75767
SNAI2: 6591"
  },
  {
    "caption": "E. qPCR analysis of epithelial and mesenchymal gene expression following ZEB1 depletion in TE1 (left) and TE2 (right) cells expressing Rab11-FIP1 shRNA relative to control cells (dotted line). Graph error bars represent mean SEM (n=3 technical replicates from three different cell passages). **p<0.01, * p<0.05, n.s. TE1 CDH1, VIM. SNAI1, SNAI2, TE2 VIM, SNAI1 (Unpaired t-test).",
    "ncbi_link": "CDH1: 999
Rab11-FIP1: 75767
SNAI1: 6615
SNAI2: 6591
VIM: 7431
ZEB1: 6935"
  },
  {
    "caption": "B. The 5'UTR of rne is bound by RNase E and non-genomically encoded A-tails are maximally recovered -9nt from the rne start codon. Known stem loop strucutres (HP1-3) and the ribosomal binding site (RBS) are shaded grey.",
    "ncbi_link": "rne: 912764"
  },
  {
    "caption": "C. RNase E binding and oligoadenylation of the pdlB-yigL dicistronic transcript. The reported RNase E cleavage site (red dashed line) and SgrS binding site (grey shading) are indicated.",
    "ncbi_link": "pdlB: 
yigL: 915148"
  },
  {
    "caption": "B. Hfq binding (blue), RNase E binding (grey), and oligoadenylation of the MicA binding site in the ompA mRNA. The MicA seed sequence is shaded blue.",
    "ncbi_link": "MicA: 2847697
ompA: 945571"
  },
  {
    "caption": "A & B (top). Sequences interacting with ChiX (A) or ompA (B) were analyzed for conserved motifs using MEME. Motifs that were enriched in the target RNAs and are shown above the heatmap with proportion of target RNAs carrying the motif (N) and the expected value for the motif (e-val). The complementary sequence motifs within ChiX or ompA are shown below the logo. (Middle) Heatmaps showing the position of predicted basepairing for each interaction within ChiX or ompA. Grey bars boxed below indicate the position of basepairing with experimentally verified mRNAs (known interactions). (Bottom) Hfq (blue) and RNase E (grey) binding sites within ChiX and ompA. Hfq and RNase E-bound sequence, and non-genomically encoded oligo(A) tails within ChiX and ompA are shown as line plots where the x-axis position correlates with heatmaps above.",
    "ncbi_link": "ChiX: 5061500
ompA: 945571"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for frdA-RyhB (A). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "frdA: 948667
RyhB: 2847761"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for zapB-RyhB (B). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "RyhB: 2847761
zapB: 948420"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for hdeA-RyhB (C). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "hdeA: 948025
RyhB: 2847761"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) hdeA-GadY (D). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "GadY: 2847729
hdeA: 948025"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for rssA-RyeB (E). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "rssA: 945725
RyeB: 2847772"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for chuA-Esr41 (F). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "Esr41: 
chuA: 915763"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for cirA-Esr41 (G). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "Esr41: 
cirA: 916751"
  },
  {
    "caption": "A-H. Base pairing patterns for the sRNA-mRNA pairs identified by CLASH were calculated using IntaRNA software (Busch et al. 2008) and are shown (left) for bfr-Esr41 (H). Point mutations and predicted sRNA seed sequences (blue shading) are indicated. (Histograms, right) Median fluorescence intensity (MFI) was assessed by FACS for mRNA-sfGFP fusions with compensatory base changes. In each case, introduction of a point mutation into an sRNA or mRNA construct (M1) is expected to reduce sRNA repression, which should be restored by combining complementary point mutants (last bar, M1-M1). A two-tailed t-test was used to calculate significance from biological triplicate cultures. *p<0.05.",
    "ncbi_link": "Esr41: 
bfr: 947839"
  },
  {
    "caption": "A-C. FACS analysis of constitutively expressed sfGFP fusions to chuA (A), cirA (B), or bfr (C) in the presence of Esr41 (orange), RyhB (blue), or a scrambled RNA control (red). The histogram shows GFP fluorescence for each sRNA-mRNA fusion.",
    "ncbi_link": "Esr41: 
bfr: 947839
cirA: 916751
chuA: 915763
RyhB: 2847761"
  },
  {
    "caption": "D. Esr41 confers resistance to Colicin 1A and 1B in the sensitive background, E. coli DH5alpha. Top agar lawns of DH5alpha expressing a control scrambled RNA (pJV300), Esr41 (pZE12::esr41), or RyhB (pZE12::ryhB) were spotted with colicins indicated (top). Zones of clearing indicate sensitivity to the tested colicin.",
    "ncbi_link": "Esr41: 
esr41: 
RyhB: 2847761
ryhB: 2847761"
  },
  {
    "caption": "E. Esr41 confers a competitive disadvantage on EHEC under iron-limiting conditions. Wild type EHEC and isogenic ∆esr41 strain (black), or EHEC ∆esr41and the chromosomally repaired strain EHEC ∆esr41::esr41 were inoculated at equal densities and cultured in MEM-HEPES media for 3 days. The proportion of each strain was determined at each time point (days) and is expressed as a ratio relative to the starting inoculum where 1 is an equal fitness (see Appended Supplementary Methods).",
    "ncbi_link": "esr41: "
  },
  {
    "caption": "C-E Mapping of the binding  region between myoVa and caldendrin using co-immunoprecipitation of cald-tagRFP  and  GFP-myoVa fragments expressed in HEK293T  cells. Arrows in D indicate the size of the respective myosin fragment. F Summary of the results from C - E.  Caldendrin binds  specifically to a fragment containing  IQ-motif 1 (amino acids  742-791), but not to any other region of myoVa, in a Ca2+-dependent manner.",
    "ncbi_link": "GFP: 
RFP: 
cald: 171051
myoVa: 17918"
  },
  {
    "caption": "B Co-sedimentation assay of GFP-tagged myosin fragment lacking the  globular tail  domain (GFP-myoVa-motor+CC) with  F-actin shows that the presence of Ca2+-caldendrin does not prevent myoV from binding  to  actin filaments. GFP-myoVa-motor+CC, as visualized by an anti-GFP antibody via western blot, co-sediments with  F-actin  (comassie blue stained SDS-PAGE), both in presence and absence of Ca2+, regardless of the presence of caldendrin.",
    "ncbi_link": "GFP: 
myosin: 
myoVa: 17918"
  },
  {
    "caption": "E Analysis of the mean squared displacement (MSD) of peroxisomes over time  (left) suggests a linear increase for all conditions. Slope analysis for MSD curves for individual cells (right) indicates that addition of  rapalog induces efficient stalling (2-way ANOVA, *** p<0.0001 as compared before and after rapalog). However, no difference between control and  caldendrin (cald) transfected cells could be observed (2-way ANOVA, Mean ± SEM; n control=14 cells, n cald=23 cells; 3 experiments).",
    "ncbi_link": "cald: 171051
caldendrin: 171051"
  },
  {
    "caption": "A Example confocal images from 10 min time-lapse imaging of control (GFP) or caldendrin (cald-GFP) transfected rat primary hippocampal neurons (DIV17) expressing an ER-marker (ER-tDimer). Yellow arrows show dendritic protrusions with a stably inserted ER (>10 min). Blue arrows indicate protrusions with a transient ER entry. Scale bar = 5 µm. B Quantification of dynamic SER  presence in protrusions of control (GFP) or  caldendrin (cald-GFP) transfected neurons. In protrusions of cald-GFP neurons, the percentage of stably localized ER (> 10 min) is increased, while transient SER visits are decreased compared to the control. (mean ± SEM, 2-way ANOVA, * p=0.0386 for  interaction, n GFP = 9, n  cald-GFP = 10; 2 experiments)",
    "ncbi_link": "GFP: 
cald: 171051
caldendrin: 171051"
  },
  {
    "caption": "C Representative  confocal  images of control (GFP) or caldendrin (cald-GFP) transfected rat primary hippocampal neurons expressing an  ER-marker (ER-tDimer). To pre-load overexpressed  caldendrin with Ca2+, neurons  were stimulated with 50 µM bicuculline for 5 min 8 hours prior to fixation and  stained with a homer1-antibody to visualize synapse-containing spines. Arrows indicate spines  that contain ER. Scale bar = 5 µm. D - F Quantification of protrusion- and spine  density and the number of SER-positive spines as shown in C. (mean ± SEM, n GFP ctrl = 24 cells, n Cald-GFP = 25 cells; 3 experiments). (D) The density of  dendritic protrusions (spines and filopodia) is increased in  cald-GFP overexpressing neurons compared to the control. (* p=0.0119, unpaired t-test). (E) The density of homer1-positive dendritic spines is increased in cald-GFP overexpressing  neurons  compared to the control. (** p=0.0049, unpaired t-test). (F) The percentage of ER-containing  dendritic spines is increased in  cald-GFP overexpressing neurons compared to the control. (* p=0.0179, unpaired t-test) G",
    "ncbi_link": "GFP: 
cald: 171051
Cald: 171051
caldendrin: 171051"
  },
  {
    "caption": "G Representative confocal images of control (GFP) or  caldendrin  (cald-GFP) transfected rat primary hippocampal neurons pre-treated with bicuculline as in C and stained  against homer1 and the spine  apparatus-marker  synaptopodin. Yellow arrows indicate synaptopodin clusters localized inside the dendritic shaft, blue arrows indicate spine-localized synaptopodin. Scale bar = 5 µm. H - J Quantification of spine density, synaptopodin  clusters and synaptopodin-positive spines as shown in G. (mean ± SEM, n GFP ctrl = 21 cells, n cald-GFP = 30 cells; 2 experiments). (H) Spine density is increased in  cald-GFP overexpressing neurons  compared to the control (in line with 5e). (** p = 0.0024, unpaired t-test). (I) The total number of synaptopodin clusters is not affected by caldendrin overexpression. (n.s., unpaired t-test). (J) The percentage of synapotpodin-positive  spines is increased in  cald-GFP overexpressing  neurons compared to the control. (**** p < 0.0001, unpaired t-test).",
    "ncbi_link": "GFP: 
cald: 171051
caldendrin: 171051"
  },
  {
    "caption": "A 10 min  time-lapse  imaging of DIV12 wild-type (cald WT), caldendrin  knock-out (cald KO), caldendrin knock-out expressing  caldendrin-GFP (cald  KO + cald-GFP) or caldendrin knock-out treated with  jasplakinolide  (cald  KO + JPK) mouse primary hippocampal neurons, additionally expressing a cell fill (maxGFP) and an ER-marker (ER-tDimer). Yellow arrows indicate protrusions with a stably anchored  ER (>10 min). Blue arrows indicate protrusions that show transient presence of  ER. Scale bar = 5 µm.",
    "ncbi_link": "GFP: 
cald: 29867
cald: 171051
caldendrin: 29867
caldendrin: 171051"
  },
  {
    "caption": "A Representative confocal  images of  mouse primary hippocampal neurons stained  against homer1 and synaptopodin. The groups compared are wild-type (cald WT), caldendrin knock-out (cald KO), caldendrin knock-out expressing caldendrin-GFP (cald  KO cald), and caldendrin knock-out treated with  jasplakinolide (cald  KO  JPK). Scale bar = 5 µm.",
    "ncbi_link": "GFP: 
cald: 29867
caldendrin: 29867"
  },
  {
    "caption": "B - C Quantification of spine density, synaptopodin clusters and synaptopodin-positive  spines  as shown in A (mean ± SEM. Kruskal-Wallis test with Dunn's multiple comparisons post-test. *** p < 0.0001. cald wt n = 34 cells, 2 experiments; cald  KO n = 33 cells, 3 experiments; cald  KO cald n = 10 cells, 1 experiment; cald  KO  JPK n = 14 cells, 1 experiment). (B) The total number of synaptopodin  clusters is unaffected by the loss of caldendrin. (C) The number of synaptopodin-positive  spines is reduced in cald KO compared to the WT neurons. This phenotype could be rescued by over-expression of caldendrin (cald KO + cald), but not by treatment with JPK (cald KO + JPK).",
    "ncbi_link": "cald: 29867
caldendrin: 29867"
  },
  {
    "caption": "Montage of Atoh7+ progenitor   division generating an RGC  (magenta dot) and a PRpr  (cyan dot). Dashed line indicates the apical side, arrowhead points to RGC axon. atoh7:GFP-CAAX (Atoh7, grey). Scale bar 10 µm.",
    "ncbi_link": "GFP: 
atoh7: 58216"
  },
  {
    "caption": "Montage of Atoh7+ progenitor  division generating an HC  (orange dot) and a PRpr  (cyan dot). Dashed line indicates the apical side. atoh7:GFP-CAAX (Atoh7, grey). Scale bar 10 µm. Montage of Atoh7+ progenitor  division generating an AC  (yellow dot) and a PRpr  (cyan dot). Dashed line indicates the apical side, arrowhead points to  basal dendrites. atoh7:GFP-CAAX (Atoh7, grey). Scale bar 10 µm.",
    "ncbi_link": "GFP: 
atoh7: 58216"
  },
  {
    "caption": "Two examples of retinas  at 48 hpf in (left) control and (right) Prdm1a  morphant (MO). Atoh7+ cells (magenta), inhibitory neurons  (yellow) and photoreceptors  (cyan) are labelled. Scale bar 50 µm. A') Close up of Crx  (cyan) signal (upper panel) and DAPI  (grey, lower panel) from Fig A, for controls (left) and Prdm1a  morphant (right). Scale bar 20 µm. Staining  for the photoreceptor cell marker  zpr-1 at 72 hpf in (left) control and (right) Prdm1a  knockdown. Atoh7+ cells (magenta),  inhibitory neurons (yellow), photoreceptors  (cyan) and zpr-1 (grey). Scale bar 50 µm. Arrowheads indicate zpr-1 staining. B') Close up of Atoh7  (magenta) and Crx  (cyan) signal (upper panel), together with Zpr-1 (grey, lower panel) from Fig B, for controls (left) and Prdm1a  morphant (right). Scale bar 20 µm. ",
    "ncbi_link": "Prdm1a: 323473"
  },
  {
    "caption": "Measurements of retinal  diameter in control (black dots) and Prdm1a  knockdown (empty dots) at 24, 36, 48 and 72 hpf. N and p values are found in Table 2.**** for p < 0.0001, Two-way Anova with Bonferroni correction. Mean and single values are indicated.",
    "ncbi_link": "Prdm1a: 323473"
  },
  {
    "caption": "Layer thickness analysis in control and Prdm1a  knockdown embryos  at 72 hpf. N = 4 embryos  (control), 6 embryos  (Prdm1a  morphant). Total thickness comparison: p = 0.0055; GCL comparison, p < 0.0001; INL comparison, ns; ONL comparison, p = 0.0369. Two-way Anova with Bonferroni correction. Mean and SD are indicated, as well as single values.",
    "ncbi_link": "Prdm1a: 323473"
  },
  {
    "caption": "Retina  at 72 hpf in (top left) control, (top right) Atoh7  knockdown, (bottom left) Ptf1a  knockdown and (bottom right) Atoh7  and Ptf1a  knockdown. Atoh7+ cells (magenta),  inhibitory neurons  (yellow) and photoreceptors  (cyan). Scale bar 50 µm, 20 µm in close-up panels.",
    "ncbi_link": "Atoh7: 58216
Ptf1a: 368662"
  },
  {
    "caption": "Layer thickness analysis  in control and morphant embryos  measured at 72 hpf. N = 9 embryos  (control), 7 embryos  (Atoh7  morphant), 7 embryos  (Ptf1a  morphant), 7 embryos  (Atoh7+Ptf1a  morphant). p values for thickness measurements are found in Table 3. Mixed effects analysis with Bonferroni correction. Mean and SD are indicated, as well as single values.",
    "ncbi_link": "Atoh7: 58216
Ptf1a: 368662"
  },
  {
    "caption": "Montage of  neurogenic progenitor division upon Atoh7  and Ptf1a  knockdown, generating two PRpr  (cyan dots). Dashed line indicates the apical side. atoh7:GFP-CAAX (Atoh7, grey). Scale bar 10 µm. Montage of neurogenic progenitor division upon Atoh7  and Ptf1a  knockdown, generating a BC  (blue dot) and a PRpr  (cyan dot). Dashed line labels the apical side, yellow arrow points at BC  apical process, white arrows point at BC  basal process. atoh7:GFP-CAAX (Atoh7, grey). Scale bar 10 µm.",
    "ncbi_link": "GFP: 
Atoh7: 58216
atoh7: 58216
Ptf1a: 368662"
  },
  {
    "caption": "Distribution of each Atoh7+ division in time  (Event plots) from 28 hpf in Atoh7  morphants, Ptf1a  morphants and double Atoh7/Ptf1a  morphants. Coloured violin plots indicate different fates, grey violin plots show all neurogenic  divisions analysed. Time  in hpf.",
    "ncbi_link": "Atoh7: 58216
Ptf1a: 368662"
  },
  {
    "caption": "E) SHP099 reduces  weight of control (p-LKO vector) and SHP2-depleted (shSHP2)  B16F10 tumors compared to untreated controls: p-LKO untreated (n=5), p-LKO treated with SHP099 (n=9), shSHP2 untreated (n=5), and shSHP2 treated with SHP099  (n=13). P values by analysis of variance with Dunnett's multiple comparison test; ***P<0.001. (F) Persistent depletion of SHP2 in tumors induced by shSHP2-B16F10 cells (n=5) compared to control tumors induced by p-LKO-B16F10 (n=5); tumors removed from mice 18 days after cell inoculation. ",
    "ncbi_link": "SHP2: 54390"
  },
  {
    "caption": "(A-F) Vero E6-TMPRSS2 (A, C, E) or Vero-E6  cells (B, D, F) were infected with SARS-CoV-2  WA1 at an MOI of 0.001. Supernatants were collected twice daily for two days, daily for an additional two days, and cells and supernatants were collected for a final  time point  at day 7 (for  Vero E6-TMPRSS2 cells) or day 8 (for Vero E6  cells). A, B) Viral titer was determined by  immune-focus forming assay  (focus-forming units [FFU]/mL), day 0 values are calculated based on known titer of inoculum. RNA levels were determined by RT-PCR  from cells (C, D) or viral supernatants (E, F) for each time point  using the indicated primer-probe sets. Note that CT is plotted inversely on the Y axes, so that lower RNA concentrations are shown lower on the axes. All data points represent four technical replicates from two independent experiments and are plotted as mean with error bars plotted as +/- SEM. Limit of detection for infectious titer is plotted as the minimum y value.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "(A_B)  Vero E6-TMPRSS2 (A) or Vero E6 (B) cells were inoculated with a total of 126 clinical NP swab samples representing a range of viral RNA levels, both total E RNA (Clinical Sample E  CT  detected by WHO-E primer/probe set) and  subgenomic E  RNA (CT  detected by the Mills-SgE primer set developed in this study). Culture supernatants were harvested when cells displayed CPE or at day 7 if no CPE was observed earlier, clarified, and presence (blue square) or absence (yellow circle) of SARS-CoV-2 determined by  immuno-focus assay.",
    "ncbi_link": "SgE: 43740570
subgenomic E: 43740570
TMPRSS2: 7113"
  },
  {
    "caption": "(A-B) Supernatants from the panel of infected (A) Vero E6-TMPRSS2 and (B)  Vero E6  cells were harvested when CPE was observed and the viral titer (FFU/mL measured by  focus forming assay) was determined for the final time point  of each sample that successfully isolated. Samples are colored according to the day CPE was observed and the sample was harvested. Total E RNA  CT of the original clinical sample used for viral isolation is plotted on the X axis. Data shown is from the subset of samples that successfully isolated in each cell line. Limit of detection for infectious titer is 400 FFU/mL.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "(A) The amount of subgenomic E RNA in the panel of clinical samples used to infect  Vero E6-TMPRSS2 cells was measured using a previously-published primer-probe set (Wölfel-sgE)",
    "ncbi_link": "subgenomic E: 43740570
TMPRSS2: 7113"
  },
  {
    "caption": "(B) For a subset of 85 NP swab samples for which sufficient material remained, SARS-CoV-2 negative-strand E  RNA levels were determined by strand-specific  RT-PCR with tagged primers. Data information: Culture supernatants were harvested when cells displayed CPE or at day 7 if no CPE was observed earlier, clarified, and presence (blue square) or absence (yellow circle) of infectious SARS-CoV-2  determined by immuno-focus assay.",
    "ncbi_link": "negative-strand E: 43740570"
  },
  {
    "caption": "Levels of the cellular housekeeping genes GAPDH and 18S rRNA, negative-strand E (negE), and sgE relative to total levels of E RNA were measured in infected cells, clarified supernatants and virus concentrated through a sucrose  cushion by ultracentrifugation. Data points represent four technical replicates from two independent experiments (Cell and Supernatant) or three replicates (Concentrated Virus) and are normalized to the total levels of E for each sample, plotted as mean with error bars plotted as +/- SEM.",
    "ncbi_link": "18S rRNA: 
negative-strand E: 43740570
sgE: 43740570
GAPDH: 103218453"
  },
  {
    "caption": "TRF1 immunofluorescence of the lungs. Notice the absence and presence of TRF1 signal in the carcinomas and surrounding healthy tissue of Trf1Δ/Δ mice, respectively.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "Analysis of Trf1 excision by PCR. Notice the completed excision in carcinomas of Trf1lox/lox lungs.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "Tumor growth curve of Trf1+/+K-Ras+/G12Vp53+/+ and Trf1Δ/ΔK-Ras+/G12Vp53+/+ measured by computed tomography (CT).Quantification of the number and size of Trf1+/+K-Ras+/G12Vp53+/+ and Trf1Δ/ΔK-Ras+/G12Vp53+/+carcinomas at death point.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Percentage of tumors that have deleted Trf1 quantified by TRF1 immunofluorescence after mice had been sacrificed. Post-mortem analysis of Trf1 deletion in each tumor revealed that none of the Trf1lox/lox K-Ras+/G12V p53+/+ ones had excised Trf1.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Tumor growth curve and tumor growth slope of Trf1+/+ K-Ras+/G12V p53−/− and Trf1−/− K-Ras+/G12V p53−/− measured by CT.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Tumor maximal section of Trf1+/+K-Ras+/G12Vp53−/− and Trf1Δ/ΔK-Ras+/G12Vp53−/−lungs measured by histological analysis before death point by CT.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Maximum 18F-FDG-glucose uptake by Trf1+/+K-Ras+/G12Vp53−/− and Trf1Δ/ΔK-Ras+/G12Vp53−/−tumors 22 weeks after infection by positron emission tomography (PET).Representative PET-CT image of Trf1+/+K-Ras+/G12Vp53−/− and Trf1Δ/ΔK-Ras+/G12Vp53−/−lungs.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "Survival curve of Trf1+/+ K-Ras+/G12V p53−/− and Trf1−/− K-Ras+/G12V p53−/− mice.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749
p53: 22059"
  },
  {
    "caption": "A-C The latency (A), volume (B), and weight (C) of subcutaneous tumors generated by control and Trf1-downregulated K-RasG12V-transformed lung cells in athymic mice.D Representative images of the subcutaneous tumors.",
    "ncbi_link": "K-Ras: 16653
Trf1: 21749"
  },
  {
    "caption": "E Trf1 expression levels measured by qPCR in the injected cell line and in the generated subcutaneous tumors.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "I Representative images of aberrant giant nuclei and anaphase bridges in the Trf1-downregulated subcutaneous tumors compared to the normal nuclei of control tumors.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "J TRF1 immunofluorescence shows the downregulation of Trf1 in lung tumors of the mice intravenously injected with control and Trf1-downregulated cells.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "K Tumor area measured in the lungs of the mice intravenously injected with control and Trf1-downregulated cells.L Representative images of the lungs colonized by control and Trf1-downregulated cells, respectively.",
    "ncbi_link": "Trf1: 21749"
  },
  {
    "caption": "P Trf1 expression levels measured by qPCR in the A549 cell line infected either with sh-scrambled or sh-Trf1.",
    "ncbi_link": "Trf1: 7013"
  },
  {
    "caption": "Trf1 expression levels in the indicated tissues of wild-type and Trf1lox/lox hUBC-CreERT2 mice subjected to a tamoxifen-containing diet for 7 weeks.",
    "ncbi_link": "Cre: 
ERT2: 13983///13982
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "Representative images of TRF1 immunofluorescence and quantification of the percentage of TRF1-positive cells in skin and intestine sections of wild-type and Trf1lox/lox hUBC-CreERT2 mice subjected to a tamoxifen-containing diet for 7 weeks.",
    "ncbi_link": "Cre: 
ERT2: 13982///13983
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "Survival curve of wild-type and Trf1lox/lox hUBC-CreERT2 mice subjected to a tamoxifen-containing diet for 7 weeks.",
    "ncbi_link": "Cre: 
ERT2: 13983///13982
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "Quantification of the histological alterations observed in tamoxifen-treated Trf1lox/lox hUBC-CreERT2 mice and 4 months after tamoxifen retrieval compared to their wild-type counterparts.",
    "ncbi_link": "Cre: 
ERT2: 13983///13982
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "Quantification of blood cell populations in wild-type and Trf1lox/lox hUBC-CreERT2mice subjected to a tamoxifen-containing diet for 7 weeks and after 3 weeks and 4 months of tamoxifen retrieval.",
    "ncbi_link": "Cre: 
ERT2: 13983///13982
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "Trf1 expression levels in blood, intestine, skin, and bone marrow of Trf1lox/lox hUBC-CreERT2 mice subjected to a tamoxifen-containing diet either for 7 weeks or for 6 months and after 3 weeks tamoxifen retrieval compared to wild-type mice.",
    "ncbi_link": "Cre: 
ERT2: 13982///13983
Trf1: 21749
UBC: 7316"
  },
  {
    "caption": "F. IL-1β quantification in THP-1 wild-type cells incubated with SYK inhibitors entospletinib (n = 4 independent experiments) and R406 (n = 2 independent experiments) or in THP-1 SYKKO cells stimulated with SP/N (n = 5 independent experiments).",
    "ncbi_link": "SYK: 6850"
  },
  {
    "caption": "Coq9Q95X mice at 21 postnatal days showing the loss of corporal hair.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "Representative Western blot images of COQ9protein in kidney homogenate from Coq9+/+ (n = 4) and Coq9Q95Xmice (n = 4) at 3 months of age. Antibody sc-271892 was used to map the C-terminal region of the COQ9protein and antibody ab-104189 was used to map the internal sequence of the COQ9protein.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "High-resolution LC-MS/MS proteomic analysis of kidneymitochondria from Coq9+/+ (n = 3) and Coq9Q95Xmice (n = 3) at 3 months of age. None of the six peptides of the COQ9 protein identified in Coq9+/+mice was detected in Coq9Q95Xmice.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-F CoQ9 levels in tissue homogenates from brain (A), cerebellum (B), heart (C), kidney (D), extensor (E) and triceps surae (F) of male and female Coq9+/+ and Coq9Q95Xmice at 6 and 12 months of age. Data are expressed as mean ± SD. Statistical analysis was performed on 6-month-old Coq9+/+mice versus 6-month-old Coq9Q95Xmice and 12-month-old Coq9+/+mice versus 12-month-old Coq9Q95Xmice. **P < 0.01; ***P < 0.001. Student's t-test (n = 8 for each group).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-F Residual CoQ9 levels in tissue homogenates from brain (A), cerebellum (B), heart (C), kidney (D), liver (E) and skeletal muscle (F) of Coq9+/+, Coq9Q95X and Coq9R239X mice at 1, 3 and 5 months of age. Data are expressed as mean ± SD. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239Xmice versus Coq9+/+mice. #P < 0.05; ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239Xmice (one-way ANOVA with a Tukey's post hoc test; n = 8 for each group; numbers above columns indicate P-values of the one-way ANOVA test).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-E mRNA expression levels of Coq9 (A), Coq7 (B), Adck3 (C), Coq5 (D) and Coq6 (E) on cerebrum of Coq9+/+, Coq9Q95X and Coq9Q95X mice at 3 months of age. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239Xmice versus Coq9+/+mice. ###P < 0.001; Coq9Q95X versus Coq9R239Xmice.F-J mRNA expression levels of Coq9 (F), Coq7 (G), Adck3 (H), Coq5 (I) and Coq6 (J) on kidney of Coq9+/+, Coq9Q95X and Coq9Q95Xmice at 3 months of age. ***P < 0.001; Coq9Q95X and Coq9R239Xmice versus Coq9+/+mice. #P < 0.05; ###P < 0.001; Coq9Q95X versus Coq9R239Xmice.K-O mRNA expression levels of Coq9 (K), Coq7 (L), Adck3 (M), Coq5 (N) and Coq6 (O) on triceps surae of Coq9+/+, Coq9Q95X and Coq9Q95Xmice at 3 months of age. *P < 0.05; ***P < 0.001; Coq9Q95X and Coq9R239Xmice versus Coq9+/+mice. #P < 0.05; Coq9Q95X versus Coq9R239Xmice.",
    "ncbi_link": "Adck3: 67426
Coq5: 52064
Coq6: 217707
Coq7: 12850
Coq9: 67914"
  },
  {
    "caption": "A-D Representative Western blot and quantitation of Western blot bands of COQ7 (A), ADCK3 (B), COQ5 (C) and COQ6 (D), and VDAC1 as a loading control in the kidneys of 3-month-old mice. *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+mice. ##P < 0.01; ###P < 0.001; Coq9Q95X versus Coq9R239X mice. One-way ANOVA with a Tukey's post hoc test.E-H Representative Western blot and quantitation of Western blot bands of COQ7 (E), ADCK3 (F), COQ5 (G) and COQ6 (H), and VDAC1 as a loading control in skeletal muscle of 3-month-old mice. **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239X mice versus Coq9+/+mice. #P < 0.05; ##P < 0.01; Coq9Q95X versus Coq9R239X mice.Data information: All values are presented as mean ± SD. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test. Coq9+/+mice n = 4; Coq9Q95X and Coq9R239Xmice n = 5.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-C Mitochondrial CoQ9 levels from cerebrum (A), kidney (B) and skeletal muscle (C) of Coq9+/+ and Coq9Q95X males and females. n = 8 for each group.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "D-F CI+CIII activity in cerebrum (D), kidney (E) and skeletal muscle (F) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.G-I CII+CIII activity in cerebrum (G), kidney (H) and skeletal muscle (I) of male and female Coq9+/+ and Coq9Q95X mice. n = 6 for each group.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "J-L Blue-native gel electrophoresis (BNGE) followed by immunoblotting analysis of mitochondrial supercomplexes from Coq9+/+ (n = 3) and Coq9Q95X mice (n = 4) at 3 months of age.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-D Measurement of phosphorylating respiration (represented as State 3o, in the presence of ADP and substrates) in kidney (A) and skeletal muscle (C) from male and female Coq9+/+, Coq9Q95X and Coq9R239X mice at 3 months of age. Representative O2 consumption graphic in kidney (B) and skeletal muscle (D) from female Coq9+/+, Coq9Q95X and Coq9R239X mice.Data information: All values are presented as mean ± SD. (A, C) *P < 0.05; **P < 0.01; ***P < 0.001; Coq9Q95X and Coq9R239Xmice versus Coq9+/+mice. #P < 0.05; Coq9Q95X versus Coq9R239Xmice. One-way ANOVA with a Tukey's post hoc test. Numbers above columns indicate P-values of the one-way ANOVA test (n = 3 for each group).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-H Complex II (SDH) and complex IV (COX) histochemistry of triceps surae showing a decreased stain in 18-month-old Coq9Q95X female mice (D, H) in contrast to normal SDH and COX activity in 6- and 18-month-old Coq9+/+ (A, C, E, G), as well as 6-month-old Coq9Q95X female mice (B, F).I-L Gomori trichrome stain (TGM) of triceps surae showed no differences between 6- and 18-month-old Coq9+/+ and Coq9Q95X female mice.M-P Hematoxylin and eosin (H&E) stains of triceps surae did not reveal any structural abnormality.Data information: Scale bars: 100 μm. n = 3 for each group. Complex IV, cytochrome c oxidase (COX); complex II, succinate dehydrogenase (SDH).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A-C Voluntary wheel running test. Distance traveled on the wheel and average speed during the use of the wheel were decreased in female Coq9Q95X mice at 6 months of age (B, C).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "D Hanging wire test. Coq9Q95X female mice obtained less reaches score in the 'fall and reaches' method.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "E Open-field test. Coq9Q95X mice showed a reduction in the average distance traveled in Coq9Q95X female mice at 6 months of age.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "F Grip test: Muscle strength was not affected in Coq9Q95X mice at 6 months of age.",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "A, B KidneyCoQ9 levels in Coq9+/+, Coq9Q95X and Coq9R239Xmice treated with 2,4-diHB (+2,4-diHB) compared with the non-treated littermate (vehicle). Statistical analysis was performed on +2,4-diHBCoq9+/+, Coq9Q95X and Coq9R239Xmice versus vehicle Coq9+/+, Coq9Q95X and Coq9R239Xmice, respectively (n = 3 for each group).",
    "ncbi_link": "Coq9: 67914"
  },
  {
    "caption": "C, D CoQ10 levels in COQ9R244X skinfibroblasts treated with 2,4-diHB (+2,4-diHB, blue bars) compared with the non-treated controls (vehicle, yellow bars). Statistical analysis was performed on +2,4-diHBCOQ9R244X versus vehicle COQ9R244X (n = 4 for each group).",
    "ncbi_link": "COQ9: 67914"
  },
  {
    "caption": "(B) Gal4 DNA-binding domain fusions of MUPs were tested with Gal4 activation domain fusions of ubiquilins (murine) in Y2H.",
    "ncbi_link": "Gal4: "
  },
  {
    "caption": "(C) HEK293 cells transfected with indicated MUP-V5, myc-UBQLN1 (human), or empty vector were immunoprecipitated (IP) with anti-myc or anti-UBQLN1 antibodies. Western blot (WB) of IP and lysate were probed as indicated.",
    "ncbi_link": "UBQLN1: 29979"
  },
  {
    "caption": "(B) Mtb were incubated with lysate from HEK293 cells transfected with vector control, myc-UBQLN1, GFP, or V5-parkin. WB analysis of the input (I), 5th wash (W5), and elution (E), probed with indicated antibodies. Actin is a loading control for the cell lysate and Ag85b for the bacterial pellet.",
    "ncbi_link": "parkin: 5071
UBQLN1: 29979"
  },
  {
    "caption": "(C) Mtb were incubated with lysate from HEK293 cells transfected with myc-UBQLN1-ΔUBA, myc-UBQLN1-ΔUBL, and myc-UBQLN1-UBA. WB containing the input, 5th wash, and elution were incubated with anti-myc antibody. The predicted sizes of myc-UBQLN1-ΔUBL, myc-UBQLN1-ΔUBA, and myc-UBQLN1-UBA are 55 kD, 50 kD, and 6 kD, respectively.",
    "ncbi_link": "UBQLN1: 29979"
  },
  {
    "caption": "(D) Mtb were incubated with recombinant GST-UBQLN1, GST-UBQLN1-ΔUBL, or GST-UBQLN1-ΔUBA. WB containing the input and elution was probed with an anti-GST antibody.",
    "ncbi_link": "UBQLN1: 29979"
  },
  {
    "caption": "(A) BMDMs were infected with GFP-expressing wt Mtb or ΔesxA for 24h and immunostained with UBQLN1 antibody. IFN-γ was added 1d prior to infection as indicated. (B) Quantification of results from A from 3 independent experiments with at least 100 bacteria analyzed per experiment; ***P< 0.001, Fisher's exact test, comparing the proportion of UBQLN1 positive versus negative Mtb in indicated samples.",
    "ncbi_link": "esxA: 886209"
  },
  {
    "caption": "(D) BMDMs were transfected with siRNAs targeting UBQLN1 or a non-targeting control (siCON) and lysates were analyzed by WB using an antibody that recognizes UBQLN1 and UBQLN2. (C-D) Actin served as a loading control.",
    "ncbi_link": "UBQLN1: 56085"
  },
  {
    "caption": "(F) BMDMs were transfected with siRNAs targeting UBQLN1 or siCON and infected with live/dead Mtb strain. IFN-γ was added 1d prior to infection if indicated. %Viable bacteria were quantified 24 and 48 hpi. Data are from 2 independent experiments. *P<0.05; ***P<0.001, Fisher's exact test, comparing the proportion of viable and non-viable bacteria in indicated samples.",
    "ncbi_link": "UBQLN1: 56085"
  },
  {
    "caption": "(G) BMDMs were treated with the indicated siRNAs three days prior to infection and then activated with IFN-γ one day prior to infection with H37Rv or ΔesxA. CFU were enumerated 4 and 96 hpi. *P< 0.05, unpaired Student's t-test. Data are representative of three independent experiments.",
    "ncbi_link": "esxA: 886209"
  },
  {
    "caption": "(H) BMDMs transfected with siRNA targeting UBQLN1 or siCON were infected with wt Mtb (H37Rv) and IFN-γ was measured by ELISA",
    "ncbi_link": "UBQLN1: 56085"
  },
  {
    "caption": "(I) UBQLN1-silenced BMDMs and controls were infected with H37Rv or ΔesxA. (H-I) 24 hpi infected BMDMs were co-cultured with P25TCR-Tg CD4+ T cells, and IFN-γ was measured by ELISA. Data is representative of 3 independent experiments. *P<0.05, **P<0.005, unpaired Student's t-test. (B, F, Γ, H) Results are mean +/- SEM; ns, not significant.",
    "ncbi_link": "esxA: 886209
UBQLN1: 56085"
  },
  {
    "caption": "(C) Wt macrophages (Atg16L1flox/flox; Cre-) and autophagy-deficient macrophages (Atg16L1flox/flox Lyz-cre; Cre+) were activated with IFN-γ or not, followed by infection with the live/dead Mtb reporter strain. % viable was quantified after addition of AnTc. **P<0.005, ***P<0.0001, Fisher's exact test (in which the proportions of viable to non-viable Mtb was compared).",
    "ncbi_link": "Cre: 
Atg16L1: 77040
Lyz: 17110"
  },
  {
    "caption": "(D) Atg16L1flox/flox Cre+ and Cre- BMDMs treated with IFN-γ and infected for 24h with GFP-Mtb were immunostained for UBQLN1 and p62. The number of Mtb co-localizating with the cellular markers is shown. (C-D) At least 100 bacteria were analyzed in three independent experiments.",
    "ncbi_link": "Cre: 
Atg16L1: 77040"
  },
  {
    "caption": "(A-C) BMDMs transfected with siRNA targeting UBQLN1 or control siRNA. Images show IFN-γ treated macrophages infected with GFP-Mtb (A-B) or DsRed-Mtb (C) for 24h. Cells were immunostained for ubiquitin (Ub) with the FK2 antibody (A) or p62 (B), which are shown in red. (C) GFP-LC3 BMDMs were infected with DsRed-Mtb. LC3 is shown in green, whereas Mtb are red. (A-C) Quantification shows the percentage of Mtb that colocalized with the indicated cellular marker in macrophages that were treated with IFN-γ as indicated. Results are mean +/- SEM from two independent experiments, with at least 100 bacteria analyzed per experiment. ***P<0.001, Fisher's exact test (in which the proportion of Mtb associated with the cellular marker in a given condition was compared to the proportion found in the sample treated with siCON and IFN-γ).",
    "ncbi_link": "UBQLN1: 56085"
  },
  {
    "caption": "(A) WT and Park2-/- BMDMs were pretreated with IFN-γ, infected with GFP-Mtb for 24h, and immunostained with the FK2 antibody. Bacterial colocalization with FK2 immunoreactivity was quantified from 2 independent experiments.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "(B) Park2-/- BMDMs pretreated or not treated with IFN-γ were infected with GFP-Mtb for 24h and immunostained with UBQLN1 specific antibody; Arrows indicate Mtb co-localized with UBQLN1. ns- not significant.",
    "ncbi_link": "Park2: 50873"
  },
  {
    "caption": "(C) Park2-/- BMDMs were transfected with siRNA targeting UBQLN1 or control siRNA 3d prior to infection, treated with IFN-γ, and infected with GFP-Mtb for 24h prior to immunostaining for ubiquitin (FK2 antibody). Ubiquitin (FK2+) bacteria were quantified from two independent experiments. (A, C) **P<0.01, Fisher's exact test (comparing the proportion of FK2 positive bacteria in indicated samples). Results are mean +/- SEM. A minimum of 100 Mtb were counted in each experiment.",
    "ncbi_link": "Park2: 50873
UBQLN1: 56085"
  },
  {
    "caption": "HeLa and cyclin F Knock-Out (CCNF K/O) cells were treated with Kinase ChemoGenomic Set (KSGS) in 384 well format. After 72 Hours (h) viability was measured using rezasurin. Flowchart representation (left). Robust Z-score difference is plotted for data acquired at 1 μM concentration (right).",
    "ncbi_link": "CCNF: 899
cyclin F: 899"
  },
  {
    "caption": "Differences in viability of HeLa and CCNF K/O cells after treatment with specific Chk1i (LY2603618) at the indicated concentrations plotted on a log10 scale to measure differences in IC50.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Number of cells was measured in HeLa and CCNF K/O cells left untreated or treated with Chk1i (LY2603618) for 24h, 48h, or 72h as indicated. (n.s. = non-significant).",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Cell viability measurements using Propidium Iodide staining for HeLa and CCNF K/O cells after treatment with Chk1i (LY2603618).",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "U-2-OS cells were seeded and transfected with non-targeting siRNA siNC (Negative Control) or siCyc F. 24 hours after transfection, cells were treated with UCN-01, or Chk1i (LY2603618) at indicated concentrations for 3 days before viability was measured.",
    "ncbi_link": "Cyc F: 899"
  },
  {
    "caption": "Cell viability measurements using Propidium Iodide staining in U-2-OS cells transfected with non-targeting siNC and siCyc F and treated with Chk1i (LY2603618) as indicated.",
    "ncbi_link": "Cyc F: 899"
  },
  {
    "caption": "Intensity of γ-H2AX measured as Relative Fluorescence Units (RFU) in early S phase cells treated with Chk1i. Mean intensity of γ-H2AX fluorescence was evaluated from EdU+ cells with 2N DAPI content. Intensity of γ-H2AX measured as Relative Fluorescence Units (RFU) in replicating cells treated with Chk1i. Mean intensity of γ-H2AX fluorescence was evaluated from EdU+. Overall, cell cycle profile of HeLa and CCNF K/O cells after Chk1i treatment. Cells with 2n DAPI staining but EdU- were gated as G1 cells; cells with >2n but <4n DAPI staining but EdU- were gated as EdU- S cells; cells with >2n but <4n DAPI staining but EdU+ were gated as EdU+ S phase; cells with 4n DAPI and pH3 S10 negative staining were gated as G2 phase and cells with 4n DAPI and pH3 S10 positive as M cells. Data from at least 3 independent replicates and plotted as Mean ± SD.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Representative plots of γ-H2AX vs RPA2 signal of HeLa and CCNF K/O cells after treatment with 1μM Chk1i (LY2603618) at the indicated hours (h). Blue labeled dots represent γ-H2AX positive cells. Relates to materials section for details on representation.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Representative plots of γ-H2AX intensity vs DAPI signal of CCNF K/O cells transfected with empty GFP and GFP-CCNF untreated (top panels) and after treatment with 1μM Chk1i (LY2603618) for 20h (bottom panels). Normalised γ-H2AX intensity in CCNF K/O cells transfected with either GFP empty vector or GFP-Cyc F and treated with 1μM Chk1i for 20 hours. GFP positive cells were gated. Data from 3 independent experiments were plotted with Mean % ± SD.",
    "ncbi_link": "GFP: 
CCNF: 899
Cyc F: 899"
  },
  {
    "caption": "Representative images of neutral and alkaline comet assay from HeLa and CCNF K/O cells treated with Chk1i. Cells were treated with 1μM Chk1i for 24h before being harvested for neutral and alkaline comet assays as indicated. Quantification of comets in alkaline gels. At least 100 cells, across two slides, were analysed in each condition in two biological replicates. Data are shown as medians, with 25/75% percentile range (box) and 10-90% percentile range (whiskers). Fold changes of median values are shown in bold. p-values were calculated using the Mann-Whitney test (two-tailed). Olive tail moment = (Tail.mean - Head.mean)*Tail%DNA/100. Quantification of comets in neutral gels. At least 100 cells, across two slides, were analysed in each condition in two biological replicates. Data are shown as medians, with 25/75% percentile range (box) and 10-90% percentile range (whiskers). Fold changes of median values are shown in bold. p-values were calculated using the Mann-Whitney test (two-tailed). Olive tail moment = (Tail.mean - Head.mean)*Tail%DNA/100.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Percentage (%) of γ-H2AX positive cells in HeLa and CCNF K/O after transfection of the indicated siRNAs treated with Chk1i for 20 hours. Percent of γ-H2Ax positive cells were plotted as Mean % ± SD. Percentage (%) of hyper-RPA positive cells in HeLa and CCNF K/O after transfection of the indicated siRNAs treated with Chk1i for 20 hours. Percent of hyper RPA positive cells were plotted as Mean % ± SD.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "Relative γ-H2AX intensity in cells transfected with either Empty Vector (EV) or HA-E2F1 treated with Chk1i for 20 hours. γ-H2AX fluorescence in HA positive cells was normalized to the empty vector transfected cells and compared to cells not expressing HA.",
    "ncbi_link": "E2F1: 
HA: "
  },
  {
    "caption": "HeLa and CCNF K/O cells transfected with the indicated siRNA and treated with 1μM Chk1i (LY2603618) for 20 hours were harvested and lysed using SDS. Indicated protein were resolved by SDS page and detected by WB. TFIIH served as a loading control.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "HeLa and CCNF K/O cells were harvested and lysed using SDS. Indicated protein were resolved by SDS page and detected by WB. Ponceau S staining was used as a loading control.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "U-2-OS cells transfected with non-targeting siRNA (siNC) or with an siRNA targeting Cyc F were lysed using SDS. Whole cell lysates were analyzed by immunoblotting 48h after transfection. H3 was used as a loading control.",
    "ncbi_link": "Cyc F: 899"
  },
  {
    "caption": "HEK293T cells transfected with empty vector (EV), FLAG-cyclin F WT, FLAG-cyclin F (∆F) and FLAG-cyclin F M309A were treated with MLN4924 for 4 hours and harvested for immunoprecipitation using FLAG antibodies. Immunoprecipitates were immunoblotted as indicated.",
    "ncbi_link": "FLAG: 
cyclin F: 899"
  },
  {
    "caption": "HEK293T cells were cotransfected with MYC-tagged ubiquitin and HA-E2F1 in the presence of FLAG-cyclin F WT, FLAG-cyclin F (∆F) and FLAG-cyclin F M309A were indicated (+). HA-E2F1 was immunoprecipitated with an anti-HA resin under denaturing conditions and immunoblotted.",
    "ncbi_link": "FLAG: 
HA: 
MYC: 
ubiquitin: 
cyclin F: 899
E2F1: 1869"
  },
  {
    "caption": "HeLa and CCNF K/O cells treated with 10 μM Chk1i (LY2603618) for the indicated time points (h=hours) were harvested and lysed using SDS. Indicated protein were resolved by SDS page and detected by WB. H2B served as a loading control.",
    "ncbi_link": "CCNF: 899"
  },
  {
    "caption": "HEK293 cells transfected with empty vector (EV) or HA-E2F1 were treated with Chk1i for 20 hours and harvested for immunoprecipitation using HA antibodies. Immunoprecipitates were immunoblotted as indicated.",
    "ncbi_link": "HA: 
E2F1: 1869"
  },
  {
    "caption": "HEK293T cells were cotransfected with MYC-tagged ubiquitin and HA-E2F1 were treated with Chk1i for 20 hours and siRNA of cyclin F were indicated (+). HA-E2F1 was immunoprecipitated with an anti-HA resin under denaturing conditions and immunoblotted.",
    "ncbi_link": "HA: 
MYC: 
ubiquitin: 
cyclin F: 899
E2F1: 1869"
  },
  {
    "caption": "HEK293T cells transfected with HA-E2F1 Wild Type (WT) and HA-E2F1 lacking a CY motif (∆RxL) harvested for immunoprecipitation using HA antibodies. Immunoprecipitates were immunoblotted as indicated.",
    "ncbi_link": "HA: 
E2F1: 1869"
  },
  {
    "caption": "HEK293T cells were cotransfected with MYC-tagged ubiquitin and HA-E2F1 or HA-E2F1 ∆RxL lacking the CY motif as indicated (+). HA-E2F1 was immunoprecipitated with an anti-HA resin under denaturing conditions and immunoblotted.",
    "ncbi_link": "HA: 
MYC: 
ubiquitin: 
E2F1: 1869"
  },
  {
    "caption": "HeLa cells stably expressing HA-E2F1 WT and HA-E2F1 ∆RxL under the control of a retroviral promoter were treated with Cycloheximide (CHX) at 50 μg/ml for the indicated minutes (min) Quantification of E2F1 half-life",
    "ncbi_link": "HA: 
E2F1: 1869"
  },
  {
    "caption": "HeLa cells stably expressing an Empty Vector (EV), HA-E2F1 WT and HA-E2F1 ∆RxL under the control of a retroviral promoter were treated with Chk1i for the indicated hours (h). Indicated protein were resolved by SDS page and detected by WB. H3 was used as a loading control.",
    "ncbi_link": "HA: 
E2F1: 1869"
  },
  {
    "caption": "Relative survival (%) of HeLa cells stably expressing an Empty Vector (EV), HA-E2F1 WT and HA-E2F1 ∆RxL under the control of a retroviral promoter measured using rezasurin and compared to EV treated with Chk1i at the indicated concentrations.",
    "ncbi_link": "HA: 
E2F1: 1869"
  },
  {
    "caption": "(A) Immunoblot against MSR1 of TUBE pulldowns of MSR1 WT and KO BMDMs shows increasing amounts of ubiquitylated MSR1 upon alternative activation and further increases upon MSR1 ligation with fucoidan or oxLDL.",
    "ncbi_link": "MSR1: 20288"
  },
  {
    "caption": "(B) Msr1+/+ (WT) and Msr1-/- (KO) M0 macrophages and M2(IL-4) macrophages untreated or stimulated with the MSR1 ligands fucoidan or oxLDL (50 μg/ml, 30 min) were analysed for the phosphorylated and the total forms of JNK1/2 and MSR1. ITGAM (CD11b) serves as a loading control. Both fucoidan and oxLDL activate JNK in a MSR1-dependent manner.",
    "ncbi_link": "Msr1: 20288"
  },
  {
    "caption": "(C) IL4-activated MSR1 knock-out BMDMs were transfected with WT or K27R MSR1 and treated with 50 μg/ml Fucoidan for 1 hr. Mutation of the ubiquitylation site K27 abolishes MSR1 signalling.",
    "ncbi_link": "MSR1: 20288"
  },
  {
    "caption": "(D) qPCR data of Tnfa, Il1b and Ccl2 mRNA levels in WT and MSR1 KO M0 and M2(IL-4) BMDMs shows an MSR1-dependent increase of pro-inflammatory cytokines in response to MSR1 ligation by fucoidan.",
    "ncbi_link": "Ccl2: 20296
Il1b: 16176
MSR1: 20288
Tnfa: 21926"
  },
  {
    "caption": "(E) Inhibition of JNK by JNK-IN8 reduces expression of Tnfa and Ccl2 upon MSR1 ligation, showing that it is JNK-dependent.",
    "ncbi_link": "Ccl2: 20296
MSR1: 20288
Tnfa: 21926"
  },
  {
    "caption": "(F) Flow cytometry analysis of cell surface markers in WT and MSR1-/- M0 macrophages and M2(IL-4) macrophages untreated or stimulated with the MSR1 ligands fucoidan (50 μg/ml, 24 h). Data shows MSR1-dependent increase of the early activation markers CD54, CD69 and CD86 and a decrease of the M2 marker CD301b/Mgl2. CD11b serves as a control.",
    "ncbi_link": "MSR1: 20288"
  },
  {
    "caption": "A Immortalized Brca1F/−MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase, followed by selection with puromycin for 72 h. Cell extracts were prepared 48 h later and analysed by Western blotting as indicated. SMC1 and tubulin were used as loading controls. *non‐specific band.",
    "ncbi_link": "Cre: 
Brca1: 12189"
  },
  {
    "caption": "A Immortalized Brca1F/−MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase, followed by selection with puromycin for 72 h. Cells were arrested in mitosis with colcemid and mitotic chromosomes were processed for CO‐FISH analysis. Metaphase chromosome spreads were stained with Cy3‐conjugated leading strand telomeric PNA probe (red) and FITC‐conjugated lagging strand telomeric PNA probe (green). DNA was counter‐stained with DAPI (blue).B The frequency of chromosome‐type telomeric fusions in cells treated as in (A) was quantified as a percentage of total number of chromosomes (illustrated in Supplementary Fig S2A). A minimum of 2,000 chromosomes were scored for each treatment. Error bars represent SD of at least two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05; **P ≤ 0.01; NS, P > 0.05.",
    "ncbi_link": "Cre: 
Brca1: 12189"
  },
  {
    "caption": "A Immortalized Brca1F/− MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase, followed by selection with puromycin for 72 h. Mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe. The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion. A minimum of 2,000 chromosomes were scored for each sample. Error bars represent SD of three independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. NS, P > 0.05.",
    "ncbi_link": "Cre: 
Brca1: 12189
TRF2: 237336"
  },
  {
    "caption": "B Immortalized Brca1F/C61G MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase, followed by selection with puromycin for 72 h. The frequency of end‐to‐end chromosome‐type fusions was analysed as in (A).",
    "ncbi_link": "Cre: 
Brca1: 12189"
  },
  {
    "caption": "C-F MEFs of the indicated genotypes were infected with retroviruses expressing TRF2 and/or CtIP shRNAs, followed by selection with puromycin for 72 h. Cell extracts were prepared 48 h later and analysed by Western blotting as indicated. GAPDH was used as a loading control. *non‐specific band.",
    "ncbi_link": "CtIP: 225182
TRF2: 237336"
  },
  {
    "caption": "C-F MEFs of the indicated genotypes were infected with retroviruses expressing TRF2 and/or CtIP shRNAs, followed by selection with puromycin for 72 h. Cells treated as in (C) and (E) were arrested in mitosis with colcemid, and mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe (D, F). The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion. Error bars represent SD of two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05.",
    "ncbi_link": "CtIP: 225182
TRF2: 237336"
  },
  {
    "caption": "C-F MEFs of the indicated genotypes were infected with retroviruses expressing TRF2 and/or CtIP shRNAs, followed by selection with puromycin for 72 h. Cell extracts were prepared 48 h later and analysed by Western blotting as indicated. GAPDH was used as a loading control. *non‐specific band.",
    "ncbi_link": "CtIP: 225182
TRF2: 237336"
  },
  {
    "caption": "C-F MEFs of the indicated genotypes were infected with retroviruses expressing TRF2 and/or CtIP shRNAs, followed by selection with puromycin for 72 h. Cells treated as in (C) and (E) were arrested in mitosis with colcemid, and mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe (D, F). The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion. Error bars represent SD of two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05.",
    "ncbi_link": "CtIP: 225182
TRF2: 237336"
  },
  {
    "caption": "A Immortalized MEFs were infected with retroviruses expressing the indicated shRNAs, followed by selection with puromycin for 72 h. Cell extracts were prepared 48 h later and analysed by Western blotting as indicated. SMC1 was used as a loading control. *non‐specific band.B Quantification of the frequency of end‐to‐end chromosome‐type fusions of cells treated as in (A) represented as a percentage of fusions observed after TRF2 depletion. A minimum of 2,000 chromosomes were scored for each sample. Error bars represent SD of three independent experiments. The P‐value was calculated using an unpaired two‐tailed t‐test. NS, P > 0.05.",
    "ncbi_link": "TRF2: 237336"
  },
  {
    "caption": "Immortalized Brca1F/− MEFs were infected with retroviruses expressing the indicated shRNAs and/or Cre recombinase. Mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe. The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion. A minimum of 2,000 chromosomes were scored for each sample. Error bars represent SD of three independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. NS, P > 0.05.",
    "ncbi_link": "Cre: 
Brca1: 12189
TRF2: 237336"
  },
  {
    "caption": "D Immortalized Brca1F/−MEFs were infected with retroviruses expressing TRF2 shRNAs and/or Cre recombinase, together with a lentivirus expressing PARP1 shRNA, followed by selection with puromycin for 72 h. Cell extracts were prepared 48 h later and analysed by Western blotting as indicated. SMC1 was used as a loading control. *non‐specific band.E Quantification of the frequency of end‐to‐end chromosome‐type fusions of cells treated as in (D) represented as a percentage of fusions observed after TRF2 depletion. A minimum of 1,500 chromosomes were scored for each sample. Error bars represent SD of three independent experiments. The P‐value was calculated using an unpaired two‐tailed t‐test. NS, P > 0.05.",
    "ncbi_link": "Cre: 
Brca1: 12189
PARP1: 11545
TRF2: 237336"
  },
  {
    "caption": "A-C MEFs of the indicated genotypes were infected with retroviruses expressing the indicated shRNAs, followed by selection with puromycin for 72 h. Mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe. The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion in each experiment. A minimum of 1,200 chromosomes were scored for each sample. Error bars represent SD of two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05; NS, P > 0.05. Each graph represents a separate set of experiments.",
    "ncbi_link": "TRF2: 237336"
  },
  {
    "caption": "A-C MEFs of the indicated genotypes were infected with retroviruses expressing the indicated shRNAs, followed by selection with puromycin for 72 h. Mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe. The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion in each experiment. A minimum of 1,200 chromosomes were scored for each sample. Error bars represent SD of two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05; NS, P > 0.05. Each graph represents a separate set of experiments.",
    "ncbi_link": "TRF2: 237336"
  },
  {
    "caption": "A-C MEFs of the indicated genotypes were infected with retroviruses expressing the indicated shRNAs, followed by selection with puromycin for 72 h. Mitotic chromosomes isolated 48 h later were fixed and stained with a Cy3‐conjugated (CCCTAA)3‐PNA probe. The frequency of end‐to‐end chromosome‐type fusions is represented as a percentage of fusions observed after TRF2 depletion in each experiment. A minimum of 1,200 chromosomes were scored for each sample. Error bars represent SD of two independent experiments. P‐values were calculated using an unpaired two‐tailed t‐test. *P ≤ 0.05; NS, P > 0.05. Each graph represents a separate set of experiments.",
    "ncbi_link": "TRF2: 237336"
  },
  {
    "caption": "Circos plots of ChIP-seq data showing genome-wide enrichment of dCas9 in ring stage parasites. The 14 chromosomes are represented circularly by the outer grey bars, with chromosome number indicated in roman numerals and chromosome distances indicated in Arabic numerals (Mbp). Enrichment for intron- or promoter-targeted dCas9 (normalized to non-targeted dCas9) is shown as average reads per million (RPM) over bins of 1,000 nt. The maximum y-axis value is 1,200 RPM for the promoter-targeted dCas9 (rings represent increments of 200) and 400 RPM for the intron-targeted dCas9 (rings represent increments of 66.7). var genes are represented by red bars. An asterisk indicates an unintended binding event.",
    "ncbi_link": "var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321"
  },
  {
    "caption": "ChIP-seq data show enrichment of dCas9 in strains at ring stage expressing non-targeted "Control" (grey), var intron-targeted (blue), or var promoter-targeted (red) sgRNAs. Genome location is indicated at the top of each panel. The x-axis is DNA sequence, with genes represented by black boxes indented to delineate introns and labeled with white arrowheads to indicate transcription direction. The y-axis is input-subtracted ChIP enrichment. q-values for promoter-targeted dCas9 peaks shown are 2.22x10-289 for PF3D7_0413100 and 7.07x10-257 for PF3D7_1240400. q-values for intron-targeted dCas9 peaks shown are 2.03x10-76 for PF3D7_412700, 6.81x10-46 for PF3D7_0412900, 1.53x10-62 for PF3D7_0413100, and 8.37x10-4 for PF3D7_1240900.",
    "ncbi_link": "PF3D7_412700: 812580
PF3D7_0412900: 812579
PF3D7_0413100: 4794155
var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321
PF3D7_1240400: 811443
PF3D7_1240900: 811446"
  },
  {
    "caption": "ChIP-seq (red) and RIP-seq (green) data show enrichment of DNA and RNA, respectively, from var genes in the promoter-targeted and non-targeted "Control" dCas9 immunoprecipitation from non-clonal bulk population of ring stage parasites. Genome location is indicated at the top of each panel. The x-axis is DNA sequence, with genes represented by black boxes indented to delineate introns and labeled with white arrowheads to indicate transcription direction. The y-axis is input-subtracted dCas9 ChIP enrichment in the var gene promoter-targeted dCas9 strain (red), dCas9 RIP enrichment normalized to IgG control in the var gene promoter-targeted dCas9 strain or non-targeted "Control" dCas9 strain (green), or var gene transcript levels in the promoter-targeted dCas9 strain (RPKM, grey). One replicate was performed for ChIP-seq and RNA-seq and one replicate was performed for HA and IgG control RIP-seq.",
    "ncbi_link": "var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321"
  },
  {
    "caption": "Western blot analysis of cytoplasmic (Cty) and nuclear extracts from a bulk population of ISWI-3HA-ribo parasites in the absence (-) or presence (+) of glucosamine (GlcN). ISWI-3HA is detected with an anti-HA antibody. Antibodies against aldolase (Ald.) and histone H3 are controls for the cytoplasmic and nuclear extracts, respectively. Molecular weights are shown to the right.",
    "ncbi_link": "HA: 
ribo: 938736
ISWI: 3885918"
  },
  {
    "caption": "MA plot of log2[glucosamine-treated/untreated, M] plotted over the mean abundance of each gene (A) at 12 hpi. Transcripts with a significantly higher (above x-axis) or lower (below x-axis) abundance in the presence of glucosamine are highlighted in red (q ≤ 0.05). iswi is highlighted in blue (q = 6.71x10-10) and the active var gene is highlighted in green (q = 2.53x10-5). Two and three replicates were used for untreated and glucosamine-treated parasites, respectively. p-values were calculated with a Wald test for significance of coefficients in a negative binomial generalized linear model as implemented in DESeq2 (Love et al, 2014). q = Bonferroni corrected p-value.",
    "ncbi_link": "var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321
iswi: 3885918"
  },
  {
    "caption": "Frequency plot showing the time in the IDC of peak transcript level [comparison to microarray time course in (Bozdech et al, 2003; Data ref: Bozdech et al, 2003)] for genes that are significantly down-regulated (blue) or up-regulated (yellow) following ISWI knockdown.",
    "ncbi_link": "ISWI: 3885918"
  },
  {
    "caption": "Meta-gene plot showing average ISWI enrichment (y-axis = ChIP/Input) in clonal ISWI-3HA parasites at 12 hpi from 1.5 kb upstream of the translation start site ("Start") to 1.5 kb downstream of the translation stop site ("Stop") for genes that are down- (blue) or up-regulated (yellow) upon ISWI knockdown. One replicate was used for the ISWI ChIP-seq.",
    "ncbi_link": "HA: 
ISWI: 3885918"
  },
  {
    "caption": "ChIP-seq data show enrichment of ISWI (blue) in clonal ISWI-3HA parasites at 12 hpi relative to regions of accessible chromatin ("ATAC," red). Chromatin accessibility (ATAC-seq) data were taken from the 15 hpi time point in (Toenhake et al, 2018; Data ref: Toenhake et al, 2018). Genome location is indicated at the top of the panel. The x-axis is DNA sequence, with genes represented by black boxes indented to delineate introns and labeled with white arrowheads to indicate transcription direction. The y-axis is enrichment (ChIP/Input or ATAC-seq/genomic DNA). One replicate was used for the ISWI ChIP-seq.",
    "ncbi_link": "HA: 
ISWI: 3885918"
  },
  {
    "caption": "Meta-gene plot showing average ISWI enrichment (y-axis = ChIP/Input) in clonal ISWI-3HA parasites at 12 hpi from 1.5 kb upstream of the translation start site ("Start") to 1.5 kb downstream of the translation stop site ("Stop") for all genes, which are grouped into quartiles based on their transcript levels (RPKM) at 12 hpi. Dark red represents genes with the highest transcript levels ("1st"), light red represents genes with the second highest transcript levels ("2nd"), orange represents genes with the third highest transcript levels ("3rd"), and yellow represents genes with the lowest transcript levels ("4th"). One replicate was used for the ISWI ChIP-seq and the transcription data are an average from the two replicates of the untreated ISWI-3HA clone used for the differential expression analysis.",
    "ncbi_link": "HA: 
ISWI: 3885918"
  },
  {
    "caption": "ChIP-seq data show enrichment of ISWI (blue) and H3K9ac (green) in clonal ISWI-3HA parasites at 12 hpi at the active var gene (PF3D7_1240600). RNA-seq data from this clone at 12 hpi show transcript levels for this gene (grey). Genome location is indicated at the top of the panel. The x-axis is DNA sequence, with genes represented by black boxes indented to delineate introns and labeled with white arrowheads to indicate transcription direction. The y-axis is ChIP/Input for ChIP data and RPKM for RNA-seq data. One replicate was used for each ChIP-seq and the RNA-seq data is from a single replicate from the untreated ISWI-3HA clone used for the differential expression analysis.",
    "ncbi_link": "HA: 
var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321
ISWI: 3885918
PF3D7_1240600: 811444"
  },
  {
    "caption": "Meta-gene plot showing average ISWI enrichment (y-axis = ChIP/Input) in clonal ISWI-3HA parasites at 12 hpi from 1.5 kb upstream of the translation start site ("Start") to 1.5 kb downstream of the translation stop site ("Stop") for the active var gene (PF3D7_1240600, blue) or silent var genes (yellow). One replicate was used for the ISWI ChIP-seq.",
    "ncbi_link": "var: 812899///9221962///3885989///812552///812583///814564///812819///813140///813288///812551///812598///813141///813139///814321
ISWI: 3885918
PF3D7_1240600: 811444"
  },
  {
    "caption": "(C) ParBF binding outside parSF on the F plasmid is compatible with a power-law decay. High resolution ChIP-seq performed on DLT3586 carrying the F plasmid (F1-10B). The ParB density, normalized to 1 at the first bp downstream the last parSF binding repeat after background subtraction, is displayed over 14-Kbp on the right side of parSF. Monte Carlo simulations and analytic formula are represented in red and dotted black lines, respectively. MC simulations were performed with a Freely-Jointed Chain of linear length L=15-Kbp and a cluster radius σ=75nm. The two other parameters, the Kuhn length a=10-bp and the total number of proteins on the F plasmid Nt=360 (related to the normalization constant of the protein concentration κ=0.41) were fitted from the ChIP-seq data (see text and Fig. EV2). As a benchmark for simulations, the analytics are obtained from Eq.(1) with the same parameters. Inset; The ParBF binding profile (black line) is represented as the number of nucleotide reads over 80-Kbp centered at parS. The number of reads in the Input sample (grey line) is normalized to the total number of reads in the IP sample",
    "ncbi_link": "parS: 
parSF: "
  },
  {
    "caption": "Typical E. coli cell displays foc expressed from the endogenous genetic locus of the F plasmid (F1-10B-mVenus). The nucleoid is labelled with Hu-mCherry (central). The overlay (bottom) combines the two fluorescent channels parSF inserted at the xylE locus on E. coli chromosome from DLT358",
    "ncbi_link": "parSF: 
xylE: 948529"
  },
  {
    "caption": "ParBF binding outside parSF on the F plasmid is compatible with a power-law decay. High resolution ChIP-seq performed on DLT3586 carrying the F plasmid (F1-10B). The ParB density, normalized to 1 at the first bp downstream the last parSF binding repeat after background subtraction, is displayed over 14-Kbp on the right side of parSF. Monte Carlo simulations and analytic formula are represented in red and dotted black lines, respectively. MC simulations were performed with a Freely-Jointed Chain of linear length L=15-Kbp and a cluster radius σ=75nm. The two other parameters, the Kuhn length a=10-bp and the total number of proteins on the F plasmid Nt=360 (related to the normalization constant of the protein concentration κ=0.41) were fitted from the ChIP-seq dat parSF inserted at the xylE locus on E. coli chromosome fro DLT207",
    "ncbi_link": "parSF: 
xylE: 948529"
  },
  {
    "caption": "(A) Normalized and rescaled ParBF binding profiles at different ParBF/parSF ratio. ChIP-seq density on the right side of parSF inserted at xylE were measured in DLT2075 induced (16, 28) or not (0.4) with IPTG (100 and 500 µM), or carrying HCN plasmids pZC302 (0.04) or pJYB57 (0.016), normalized as in Fig. 1C, E with the amplitudes of the curves rescaled by the indicated factors (1.2, 10 or 50) to overlap with the curves of highest amplitude. The ParB/parS ratio is calculated relative to the one of F plasmid as determined from Western blot analyses (Appendix Fig. S2B). Monte Carlo simulations and analytical formula are plotted with the same parameters as in Fig. 1E. Note (i) that the dips at ~9-kbp are not visible for the low levels of available ParB since the signal is close to the basal level and (ii) that the ChIP-seq data at 100 µM IPTG induction (16) are the same as in Fig. 1E. Inset; Same as in the main to display the density without rescaling. (B) ParBF are dispersed in the cell upon titration by HCN plasmids. ParBF-mVenus expressed from pJYB294 were imaged as in Fig. 1D in DLT3577 (left) and DLT3576 (right) carrying pZC302 and pJYB57, respectively. The number of extra parSF per cell, indicated on top of each raw, are estimated from the copy number per cell of HCN plasmids carrying 10 specific binding sites. White bars: 1 µm. (C) The size of ParBF clusters is independent of the intracellular ParBF concentration. We considered two possible evolutions of the cluster size upon variations of ParB amount in the framework of "Nucleation & caging" with corresponding schematics drawn on the right. For direct comparison with (A), all curves are displayed with a rescaling of the amplitude corresponding to the WT expression level. Top: constant ParB concentration; supposing that clusters are compact, the cluster radius σ would depend on the number m of ParB like$\ \sigma = m^{\frac{1}{3}}$. Predictions profiles, plotted at different ratio of ParB/parS, vary within the range of the experimental levels tested. Bottom: constant cluster size; ParB concentrations vary but the range of exploration remains the same resulting in overlappin",
    "ncbi_link": "parS: 
parSF: 
xylE: 948529"
  },
  {
    "caption": "(A) The formation of secondary ParBF-DNA complexes requires the box II motif. EMSA were performed with a 144-bp 32P-labelled DNA fragments (C144) carrying a single 16-bp parS binding motif. Reaction mixtures containing 100 µg.ml-1 sonicated salmon sperm DNA were incubated in the absence (-) or the presence of increasing concentrations (grey triangle; 10, 30, 100, 300, and 1000 nM) of ParBF or ParBF-3R*. Positions of free and bound probes are indicated on the left. B1 represents complexes involving the specific interaction on the 16-bp binding site, while B\"2 and B\"3 complexes represent secondary complexes involving the parSF site with one or two additional nsDNA-binding interactions, respectively (Sanchez et al,",
    "ncbi_link": "parS: 
parSF: "
  },
  {
    "caption": "(C) ParBF in vivo DNA binding in the vicinity of parSF sites requires the box II motif. ChIP-seq was performed on DLT3726 carrying parSF in the xylE chromosomal locus and expressing ParBF-3R* variant. ParBF-3R* DNA binding profile displayed the number of nucleotide reads as a function of the E. coli genomic coordinates. The peak at parSF covered approximately 950-bp, which corresponds to the 402-bp between the 1st and 10th specific binding sites and ~280-bp on each sides (representing the average size of the DNA library; see Appendix Fig. S3E). No ParBF-3R* enrichment was found on parSF-flanking DNA and elsewhere on the chromosome. Inset, zoom in on the right side of parSF over 5-Kbp with the ParB density, normalized to 1 at the first bp after the last parS binding repeat, plotted as a function of the distance from parSF. Note that a highly similar DNA binding pattern is obtained with ParBF -3R*-mVenus (strain DLT3566; Appendix Fig. S3C)",
    "ncbi_link": "parS: 
parSF: 
xylE: 948529"
  },
  {
    "caption": "(A) Schematic representation of the genomic locus of the chromosome 1 of V. cholerae with the three parS sites, named parS1-3. The rRNA operon (blue rectangle) spans the genomic coordinates 53823 to 59123 (B) ChIP-seq performed on strain N16961 is displayed as the number of nucleotide reads in function of the genomic coordinates. Correspondence to the parS1-3 location represented in (A) is indicated by grey dotted lines. The number of reads in the Input sample (grey line) is normalized to the total number of reads in the IP sample. (C) We modeled the ChIP-Seq data as in Fig.1C-E by means of MC simulations with a Freely jointed chain of size N=2000 monomers of size a=16-bp. Data are normalized after background subtraction to the read value at parS1 (genomic coordinate 62438). The best fit was achieved with σ=25nm and an amplitude κ=0.15 leading to Nt~50 ParB on the chromosome. In the MC simulation, we accounted for the finite width of the distribution around parS sites by including the average fragment size of the DNA librar",
    "ncbi_link": "parS: "
  },
  {
    "caption": "ChIP-sequencing assays were performed on DLT2075 (xylE::parSF) expressing ParBF grown in exponential (expo) or stationary (stat) phases with addition of rifampicin when indicated (+Rif). The assays have been performed in duplicate for the +Rif and once for the stationary phase experiments. (A) ParBF DNA binding around parSF is independent of active transcription. The color-coded ParBF profiles are represented over 50-Kbp as the relative ParB density normalized to 1 at the first bp after the last parSF binding site. Loci A, C, E and F are defined in Appendix Fig. S1A. (B) The dips and peaks are highly similar in the three indicated conditions. Same as in (A) with zoom in on the right side of parSF up to 9-Kpb and normalization to 1 at genomic coordinate 230. The dotted line corresponds to the analytics description of "Nucleation and caging" (see details in Fig. 1C-E). (C) ParBF binding profile upstream of the locus A. Same as in (A) with zoom in from -6.5 to -16.5-Kbp by normalization to 1 at genomic coordinate -6.5-Kbp (upstream of the dip at the locus A). The ParBF DNA binding profile remains compatible to a power-law, represented by the analytics description (dotted line), upstream of the locus A in stationary phase (black) and in exponential phase (blue). Also, the dips and peaks are highly similar in both conditions. These data are not in favor of the "1D-spreading" or the "Spreading and bridging" models that predicts a basal uniform distribution or a linear decrease after a barrier, respectively (Broedersz et al, 2014). (D) The promoter region at locus A prevents ParBF DNA binding. Chip-seq assays were performed in isogenic xylE::parSF strains (DLT2075; black curve) in which the locus A is replaced by a kanamycin gene (DLT3651; red curve). The assay in the ∆(locus A) genomic context has been performed once. The relative ParB density as a function of the distance from parSF is",
    "ncbi_link": "parSF: 
xylE: 948529"
  },
  {
    "caption": "(a) Densitometric analysis relative to actin of A53T α-synuclein clearance in stable inducible PC12 cell line expressing A53T α-synuclein. Transgene expression was induced with doxycycline for 48 h, and then switched off (by removing doxycycline), with drug (all 1 μM) or DMSO (control) treatment for 24 h. Control condition is set to 100%. Error bars show s.e.m.",
    "ncbi_link": "α-synuclein: 6622"
  },
  {
    "caption": "(e) The proportions of EGFP-positive cells with EGFP-HDQ74 aggregates in wild-type (Atg5+/+) and knockout (Atg5−/−) Atg5 MEFs, transfected with EGFP-HDQ74 for 4 h and then treated for 48 h with drugs (all 1 μM) or DMSO (control). Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(a) Densitometric analysis relative to actin of A53T α-synuclein clearance in stable inducible PC12 cell line expressing A53T α-synuclein. Transgene expression was induced with doxycycline for 48 h, and then switched off (by removing doxycycline), with drug (all 1 μM) or DMSO (control) treatment for 24 h. Control condition is set to 100%. Error bars show s.e.m.",
    "ncbi_link": "α-synuclein: 6622"
  },
  {
    "caption": "(a) A53T α-synuclein clearance in stable PC12 cells as in Figure 1a, treated with or without 1 μM rilmenidine, 1 mM dibutyl-cAMP (db-cAMP), 24 μM forskolin or 500 μM 2′5′-dideoxyadenosine (2′5′ddA) for 24 h. Note that control clearance levels for a given substrate may vary from figure to figure, due to different exposures of blots, which aid illustration of agents that either increase or retard clearance.",
    "ncbi_link": "α-synuclein: 6622"
  },
  {
    "caption": "(f) COS-7 cells, transfected for 4 h with EGFP-HDQ74 along with empty vector (pcDNA3.1), dominant-negative S17N Rap2B (DN Rap2B) or wild-type PLC-ε (1:3 ratio), were assessed for the proportions of EGFP-positive cells with aggregates after 48 h. Error bars show 95% confidence interval.",
    "ncbi_link": "PLC-ε: 51196
Rap2B: 5912"
  },
  {
    "caption": "(g) Endogenous LC3-II levels in COS-7 cells transfected with a dominant-negative Rap2B (DN Rap2B) for 4 h were assessed after 48 h expression.",
    "ncbi_link": "Rap2B: 5912"
  },
  {
    "caption": "(h) The proportions of EGFP-positive COS-7 cells with aggregates, transfected with EGFP-HDQ74 along with empty vector (pcDNA3.1) or dominant-negative Rap2B (1:3 ratio) for 4 h, were treated with or without 10 μM 8-CPT-2Me-cAMP for 48 h. Error bars show 95% confidence interval.",
    "ncbi_link": "Rap2B: 5912"
  },
  {
    "caption": "(i) COS-7 cells, transfected with EGFP-HDQ74 and dsRed2 or cytosolic dsRed2-IP3 kinase A (1:3 ratio) for 4 h, were assessed at 48 h post-transfection for aggregation and cell death (as in Fig. 1c). Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.",
    "ncbi_link": "IP3 kinase A: 3706"
  },
  {
    "caption": "(e) COS-7 cells transfected with empty vector (pcDNA3.1) or wild-type PLC-ε for 4 h and treated with or without 50 μM calpeptin for 48 h post-transfection were assessed for the proportion of EGFP-positive cells with EGFP-HDQ74 aggregates. Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.",
    "ncbi_link": "PLC-ε: 51196"
  },
  {
    "caption": "(b) HeLa cells were transfected with EGFP-HDQ74 construct along with siGLO (control siRNA) in presence or absence of calpain 1 or calpain 2 siRNA (1:3 ratio) for 96 h. EGFP- and siGLO-positive cells were assessed for aggregation and cell death as in Figure 1c. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain 1: 823
calpain 2: 824"
  },
  {
    "caption": "(c) HeLa cells, transfected with siGLO or siRNAs for calpain 1 or calpain 2 for 96 h, were analyzed with anti-calpain 1 or anti-calpain 2 domain III antibodies.",
    "ncbi_link": "calpain 1: 823
calpain 2: 824"
  },
  {
    "caption": "(f) COS-7 cells, transfected with EGFP-HDQ74 along with empty vector (pcDNA3.1) or constitutive active (CA) m-calpain (1:3 ratio) for 48 h, were assessed for aggregation and cell death as in Figure 1c. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(g) SK-N-SH cells, transfected with EGFP-HDQ74 along with empty vector (pcDNA3.1) or constitutive active m-calpain (1:3 ratio) for 4 h, were subsequently treated with DMSO (control), 1 μM verapamil or 1 μM clonidine for 48 h. The proportions of EGFP-positive cells with aggregates were assessed as in Figure 1c. Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(a) The proportions of EGFP-positive MEFs with aggregates, transfected with EGFP-HDQ74 and pcDNA3.1 (empty vector) in Atg5+/+ cells, or transfected with EGFP-HDQ74 and pcDNA3.1, WT Atg5 or K130R Atg5 constructs in Atg5-/- cells for 4 h (1:3 ratios), were treated for next 48 h with or without 10 μM calpastatin. All data are from the same experiment, but odds ratios for reference conditions in specific experiments have been set to 1, to facilitate comparisons. Atg5-/- cells had increased EGFP-HDQ74 aggregates compared to Atg5+/+ cells. Error bars show 95% confidence interval.",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(b) HeLa cells were transfected with siGLO (control) with or without calpain 1 siRNA or calpain 2 siRNA (1:3 ratio) for 96 h, followed by transfection with EGFP-LC3 construct for 4 h. Cells were fixed after a further 2 h. The proportions of transfected cells with >5 EGFP-LC3 vesicles were assessed. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain 1: 823
calpain 2: 824"
  },
  {
    "caption": "(e) COS-7 cells, transfected with myc-LC3 and EGFP-C1 with pcDNA3.1 (empty vector) or constitutively active (CA) m-calpain (1:1:3 ratio) for 4 h, were analyzed after 24 h post-transfection for LC3-II levels by immunoblotting with anti-myc antibody. Error bars show s.e.m.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(f) COS-7 cells, transfected with EGFP-LC3 and pcDNA3.1 (empty vector) or CA m-calpain (1:3 ratio) for 4 h and fixed 24 h post-transfection, were assessed for proportions of EGFP-positive cells with >5 EGFP-LC3 vesicles. Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(c) Aggregation in COS-7 cells transfected with either pcDNA3:1 (empty vector) or constitutively active (CA) m-calpain and EGFP-HDQ74 (3:1 ratio) for 4 h and then treated with or without 500 μM 2′5′ddA for 48 h. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(d) HeLa cells transfected with control or Gsα siRNA for 72 h were analyzed for Gsα levels by immunoblotting with anti-Gsα antibody. Aggregation was assessed in HeLa cells transfected with control or Gsα siRNA and EGFP-HDQ74 for 72 h. Error bars show 95% confidence interval.",
    "ncbi_link": "Gsα: 2778"
  },
  {
    "caption": "(e) Endogenous LC3-II levels in HeLa cells transfected with control or Gsα siRNA for 72 h.",
    "ncbi_link": "Gsα: 2778"
  },
  {
    "caption": "(g) Endogenous LC3-II levels in HeLa cells transfected with control or Gsα siRNA for 72 h and treated with or without 400 nM bafilomycin A1 for the last 4 h. Densitometric analysis is relative to actin. Error bars show s.e.m.",
    "ncbi_link": "Gsα: 2778"
  },
  {
    "caption": "(h) The proportions of EGFP-positive HeLa cells with aggregates, transfected with control or Gsα siRNA for 48 h, and then retransfected together with pcDNA 3.1 (empty vector) or CA m-calpain and EGFP-HDQ74 (3:1 ratio) for a further 48 h. Error bars show 95% confidence interval. ***P 0.001; **P 0.01; *P 0.05; NS, nonsignificant.",
    "ncbi_link": "calpain: 825///824///823
Gsα: 2778"
  },
  {
    "caption": "(a) The proportions of EGFP-positive COS-7 cells with aggregates or cell death, after transfection with EGFP-HDQ74 and rheb or pcDNA3.1 (empty vector) (1:3 ratio) for 4 h and treatment with or without 10 μM calpastatin or 50 μM calpeptin for 48 h post-transfection. The control condition for assessing the effect of calpain inhibitors in rheb-transfected cells was taken as 1. Error bars show 95% confidence interval.",
    "ncbi_link": "rheb: 6009"
  },
  {
    "caption": "(b) The proportions of EGFP-positive COS-7 cells with >5 EGFP-LC3 vesicles, transfected with EGFP-LC3 and pcDNA3.1 (empty vector) or rheb (1:3 ratio) for 4 h and treated with or without 10 μM calpastatin or 50 μM calpeptin for 24 h post-transfection. Error bars show 95% confidence interval.",
    "ncbi_link": "rheb: 6009"
  },
  {
    "caption": "(c) The proportions of EGFP-positive COS-7 cells with aggregates, transfected with EGFP-HDQ74 and constitutively active (CA) m-calpain or pcDNA3.1 (empty vector) (1:3 ratio) for 4 h and treated with or without 0.2 μM rapamycin for 48 h post-transfection. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "(d) The proportions of EGFP-positive COS-7 cells with >5 EGFP-LC3 vesicles, transfected with EGFP-LC3 and CA m-calpain or pcDNA3.1 (empty vector) (1:3 ratio) for 4 h and treated with or without 0.2 μM rapamycin for 24 h post-transfection. Error bars show 95% confidence interval.",
    "ncbi_link": "calpain: 825///824///823"
  },
  {
    "caption": "A. PCR analysis of the human H49K variant of the ATPIF1 and rtTA constructs in wild-type (wt), ACTA1-rtTA (T), ATPIF1H49K-TRE (H) or double transgenic (T/H) mice.",
    "ncbi_link": "ACTA1: 58
ATPIF1: 93974"
  },
  {
    "caption": "(B WB expression of the human (h) ATPIF1 protein in Skm (B extracts. hATPIF1 is only expressed in Skm from ATPIF1H49K|T/H mice. HSP60 are shown as loading controls. n= 3 mice/genotype.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "(C) Immunofluorescent staining of wt and ATPIF1H49K|T/H hindlimb muscle slices with hATPIF1 and βF1 antibodies. Images are representative of 3 mice/genotype, 5 fields/mouse. hATPIF1 H49K is only expressed in T/H mice.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "D) WB expression of the human + mouse (m+h) ATPIF1 protein in Skm D), brain, liver, and WAT (D) extracts. hATPIF1 is only expressed in Skm from ATPIF1H49K|T/H mice. α-tubulin are shown as loading controls. n= 3 mice/genotype.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "E. Polarographic profiles of isolated mitochondria from wt (lower trace) and ATPIF1H49K|T/H (upper trace) animals. Histograms show a reduction in state 3 respiration consistent with the inhibition of ATP synthase in ATPIF1H49K|T/H mice. Bars are the mean ± s.e.m. of n= 3 mice/genotype, 3 traces/mouse; OL, oligomycin; Ant A, antimycin A.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "A. Representative images of mice and body weight graph following the expression of mitochondrial ATPIF1H49K (days of doxycycline) (wt, n= 12; LowOXPHOS, n= 12).",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "(K, L). 14C(u)-glucose uptake (K) and oxidation to CO2 (L) in myocytes expressing or not the ATP synthase inhibitor ATPIF1H49K. Bars are the mean ± s.e.m. of n= 3 experiments, 6 replicas/condition. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype *p <0.05 when compared to wt by ANOVA and Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "T. LD formation upon ATP synthase inhibition (ATPIF1H49K) in starved myocytes after 24 hours of palmitate supplementation in the presence or absence of BCAA. Blue: DAPI, nuclei; green: BODIPY-positive LDs. Histograms show the quantification expressed as the number of LDs/nuclei. Bars are the mean ± s.e.m. of n= 3 experiments, 12 fields/condition. U. LD formation upon ATP synthase inhibition (5µM oligomycin) in myocytes after 24 hours of palmitate supplementation. Histograms show the quantification expressed as fold of control of the BODIPY/DAPI fluorescence intensity. 7 fields/condition. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype *p <0.05 when compared to wt by ANOVA and Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "D, E). oxidation (D) and incorporation into lipids (E) in myocytes expressing or not ATPIF1H49K. Bars are the mean ± s.e.m. of n= 3 experiments, 6 replicas/condition. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype *p <0.05 when compared to wt by ANOVA or Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "M. Skm relative expression of the GLUT1, GLUT3, PPARβ/δ and PGC1α by qPCR (wt, n= 5; LowOXPHOS, n= 5). Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype *p <0.05 when compared to wt by ANOVA or Student's t-test.",
    "ncbi_link": "PPARβ/δ: 19015
PGC1α: 19017
GLUT1: 20525
GLUT3: 20527"
  },
  {
    "caption": "N. qPCR relative expression of myokines (wt, n= 5; LowOXPHOS, n= 5). Red or blue color represents higher or lower % expression, respectively, compared to that in wt. SPARC, osteonectin; OSTN, musclin; LIF, interleukin 6 family cytokine; FKN, fractalkine; FSTL1, follistatin-like protein 1; FNDC5, irisin; ADIPOQ, adiponectin. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype *p <0.05 when compared to wt by ANOVA or Student's t-test.",
    "ncbi_link": "adiponectin: 11450
ADIPOQ: 11450
FKN: 13051
fractalkine: 13051
FNDC5: 384061
irisin: 384061
follistatin-like protein 1: 14314
FSTL1: 14314
interleukin 6 family cytokine: 16878
LIF: 16878
musclin: 239790
OSTN: 239790
osteonectin: 20692
SPARC: 20692"
  },
  {
    "caption": "I. MitoSox staining in myocytes expressing or not ATPIF1H49K. The right histogram shows the quantification of mitochondrial ROS. Bars are the mean ± s.e.m. of n= 3 experiments, 12 replicas/condition. Data information: Bars are the mean ± s.e.m. of the indicated (n) mice/genotype. *p <0.05 when compared to wt by Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "I. MitoSox staining in myocytes expressing or not ATPIF1H49K. The left scheme illustrates where each ETC inhibitor works. The right histogram shows the quantification of mitochondrial ROS. Bars are the mean ± s.e.m. of n= 3 experiments, 12 replicas/condition. Data information: *, # p <0.05 when compared to wt or LowOXPHOS, respectively, by ANOVA and Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "J. MitoSox staining in myocytes expressing or not ATPIF1H49K. The left scheme illustrates where each CII inhibitor works. The right histogram shows the quantification of mitochondrial ROS. Bars are the mean ± s.e.m. of n= 3 experiments, 12 replicas/condition. Data information: *, # p <0.05 when compared to wt or LowOXPHOS, respectively, by ANOVA and Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "(F, G) FFA β-oxidation in C2C12 myocytes transfected with CRL or ATPIF1H49K plasmids (F) and in primary myotubes from wt and LowOXPHOS mice (G), treated (green bars) or not with 2 µM edaravone. Bars are the mean ± s.e.m. of n= 3 experiments, 9 replicas/condition. Data information: *p <0.05 when compared to wt by ANOVA and Student's t-test.",
    "ncbi_link": "ATPIF1: 93974"
  },
  {
    "caption": "C. qPCR relative expression of TNFα and PGC1α in myocytes treated for 24 h with 2μM edaravone (green bars), 10nM MitoQ (purple bars) or 1 mM NAC (blue bars). 6 replicas/condition.",
    "ncbi_link": "PGC1α: 19017
TNFα: 21926"
  },
  {
    "caption": "A. Survival curves for WT and Spns2-/- CLP  models without antibiotic therapy within 72 hours (n=13 for each group). Data information: Data are presented as percentage (A N represents biological replicates. P values were determined by log-rank test (A *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "E. Survival curves for WT (n=12) and Spns2-/- (n=17) CLP  models receiving meropenem  treatment within 7 days. Data information: Data are presented as percentage E) N represents biological replicates. P values were determined by log-rank test E) *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "B. Oxygen consumption rates  (OCR) and quantifications of  basal respiration, maximal respiration, ATP  production, and proton leakage in resting WT, Spns2-/-, and 1 μM S1P  pre-treated Spns2-/- PMs  (n=4 for each group). Data information: Data are presented as mean ± s.e.m. (B N represents biological replicates. P values were determined by unpaired t-test. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "A. Fragmented mitochondrial morphology  in Spns2-/- PMs  revealed by  ransmission electron microscopy. Zoom-in view of the area in the red frame are shown below. Scale bars: 1 μm. B. The lengths of 38 and 47 mitochondria  from WT and Spns2-/- PMs, respectively (n=1 for each group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "H. Protein levels of Slc25a12  and Slc25a13  in WT, Spns2-/-, and 1 μM S1P  pre-treated Spns2-/- PMs  (n=3 for each group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "F. Attenuated activities  of total SOD  and catalase  in oxamate- and S1P-treated Spns2-/- PMs  (n=3 to 4 for each group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. *P < 0.05; **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "A, B. Reduced gene expression  of inflammatory cytokines in Spns2-/- PMs  treated with either oxamate  (A) or mitoquinone  (B) (n=3 per time point  for each group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "C. Activation of Spns2/S1P  signaling and suppression of the lactate-ROS  axis promoted the survival of Spns2-/- sepsis  models induced by heat-killed E. coli through the alleviation of hyerinflammation  (n=5 for Spns2-/- control group; n=4 for each treatment group). Data information: Data are presented as mean ± s.e.m. N represents biological replicates. P values were determined by unpaired t-test. **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "A. S1P  treatment restored inflammatory response in Spns2-/- PMs  after 6 hours post- LPS  challenge (n=3 per time point for each group). Data information: Data are presented as mean ± s.e.m. (A N represents biological replicates. P values were determined by unpaired t-test (A *P < 0.05; **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "B. Enhancement of Spns2/S1P  signaling significantly improved the survival  of CLP  models without antibiotic therapy (n=8 for Spns2-/- saline  group; n=14 for Spns2+/- group; n=12 for Spns2-/- S1P  treatment group). Data information: Data are presented as percentage (B). N represents biological replicates. P values were determined by log-rank test (B). *P < 0.05; **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "C. Enhancement of Spns2/S1P  signaling restored inflammatory response in Spns2-/- CLP  models at 12 hours post-infection (n=6 for each group). Data information: Data are presented as mean ± s.e.m. C) N represents biological replicates. P values were determined by unpaired t-test C) *P < 0.05; **P < 0.01; ***P < 0.001.",
    "ncbi_link": "Spns2: 100270678"
  },
  {
    "caption": "(C) End fusion analysis for domain deletion mutants of Rap1. NotI-digested genomic DNA  from nitrogen-starved cells was analyzed by pulsed-field gel electrophoresis  (PFGE) and Southern blot with probes specific for the terminal C, I, L, and M fragments from  chromosomes  I  and II.",
    "ncbi_link": "Rap1: 2540115"
  },
  {
    "caption": "(D) PFGE  analysis as in (C) for nitrogen-starved cells harboring N-terminal truncation mutants of Rap1. All mutants were V5-tagged at their C-terminus.",
    "ncbi_link": "V5: 
Rap1: 2540115"
  },
  {
    "caption": "(A)  Telomere   length analysis of cells from different sequential restreaks following introduction of Poz1-V5-Rap1_491-693 into rap1∆ cells. Telomere  length was assessed by Southern blotting  of EcoRI-digested genomic DNA  probed with a telomere  specific probe. (B) PFGE  analysis of nitrogen-starved Poz1-V5-Rap1_491-693 cells after 5 and 14 restreaks.",
    "ncbi_link": "V5: 
Poz1: 2542244
rap1: 2540115
Rap1: 2540115"
  },
  {
    "caption": "(C) Telomere   length analysis of cells with  Rap1∆RCT fused to Taz1  or Poz1  with intervening V5  tag. The fusion protein was integrated at the endogenous rap1  locus in the context of taz1∆ or poz1∆, respectively. Different sequential restreaks following introduction of the fusion construct were analyzed. (D) PFGE  analysis for nitrogen-starved Rap1∆RCT-V5-Taz1  and Rap1∆RCT-V5-Poz1  from 2nd restreak.",
    "ncbi_link": "V5: 
Poz1: 2542244
poz1: 2542244
rap1: 2540115
Rap1: 2540115
Taz1: 2542313
taz1: 2542313"
  },
  {
    "caption": "(B) PFGE  analysis of cells containing plasmids of  Rap1_440-693 with mutations of the amino acids identified in (A) in the context of rap1∆. Cells were subjected to nitrogen-starvation after recovery from transformation (Restreak 0). (C) PFGE  analysis of nitrogen-starved cells harboring the same mutations after 5 restreaks on plates (approximately 110 generations). (D) Quantification of (B) and (C) using Fiji. The y-axis shows the percentage of intensity represented by the three fusion bands (I+L, I+M and L+M) relative to the total intensity of the fused and unfused signals. WT: wildtype  Rap1_440-693.",
    "ncbi_link": "Rap1: 2540115
rap1: 2540115"
  },
  {
    "caption": "(B) Western blot  analysis of N-terminally V5-tagged truncation mutants using anti-V5  antibody. Anti-α-tubulin was used as loading control. Quantification of Rap1  mutant protein levels relative to WT normalized to α-tubulin is shown beneath the gel.",
    "ncbi_link": "V5: "
  },
  {
    "caption": "(C) Telomere   length analysis  of the mutants by Southern blot  with telomere  specific probe. All mutants are V5-tagged except for ∆491-638 untagged (lane 7).",
    "ncbi_link": "V5: "
  },
  {
    "caption": "(D) PFGE  analysis of the same strains in (C) that were nitrogen-starved. (E) PFGE  analysis of nitrogen-starved internal deletion mutants in poz1∆ background.",
    "ncbi_link": "poz1: 2542244"
  },
  {
    "caption": "(A) PFGE  analysis of nitrogen-starved N-terminally V5-tagged full length Rap1  mutants. All mutants were integrated at the endogenous rap1  locus. M5A is the mutation of all 5 non-alanine amino acids under selection in the p-patch to alanine. (B) PFGE  analysis of nitrogen-starved N-terminally V5-tagged rap1_440-693 mutants integrated at the endogenous rap1  locus.",
    "ncbi_link": "V5: 
rap1: 2540115
Rap1: 2540115"
  },
  {
    "caption": "(C) PFGE  analysis of nitrogen-starved rap1  mutants in poz1∆ background.",
    "ncbi_link": "poz1: 2542244
rap1: 2540115"
  },
  {
    "caption": "(D) PFGE  analysis of nitrogen-starved rap1  mutants in  ppm1∆ background. Untagged Rap1   are in lanes 1-2 and N-terminally V5-tagged in lanes 3-7.",
    "ncbi_link": "V5: 
rap1: 2540115
Rap1: 2540115
ppm1: 2541346"
  },
  {
    "caption": "(A) ChIP-qPCR  analysis of N-terminally V5-tagged WT, F545L and M6 mutants of Rap1. Untagged Rap1   was used as a control. Bars represent mean of percentage of DNA   precipitated with anti-V5  antibody conjugated beads relative to input DNA. Error bars represent SEM. N= 4 biological replicates. Two-tailed unpaired Student's t-test was performed and significance is indicated. ***: p < 0.001, **: 0.001 ≤ p < 0.01, n.s.: p>0.05. (B) ChIP-qPCR  analysis of N-terminally V5-tagged WT, F545L and M6 mutants of Rap1  in poz1∆ background performed as in (A). N= 4 biological replicates. Statistical analysis is the same as (A).",
    "ncbi_link": "V5: 
poz1: 2542244
Rap1: 2540115"
  },
  {
    "caption": "(C) Single-stranded overhang measured by denaturing gel electrophoresis of duplex-specific nuclease  digested genomic DNA  and Southern blot with oligonucleotide probes specific for the G-strand (top panel) and  C-strand (bottom panel). WT, F545L and M6 mutants of Rap1  in the presence or absence of poz1  or ppm1  were analyzed. A 21-mer of (GGTTACA)3 was used as a positive control and size marker for  G-strand and a (TGTAACC)3 oligo was used for the  C-strand.",
    "ncbi_link": "poz1: 2542244
Rap1: 2540115
ppm1: 2541346"
  },
  {
    "caption": "(B) Stacking bar chart showing telomere  distribution (labeled by Pot1-GFP) in each of the three zones. 100 telomere  foci were quantified per sample. Chi square tests were performed by comparing the rap1  mutants to WT or bqt4∆. Significance is indicated. ***: p < 0.001.",
    "ncbi_link": "bqt4: 2540694
rap1: 2540115"
  },
  {
    "caption": "(C) Yeast two hybrid assay  probing interaction  between Rap1  and Bqt4. WT and mutants of Rap1  were fused to the DNA-binding domain (BD) in pGBKT7. Bqt4   and Taz1   were fused to the Gal4  activation domain (AD) in pGADT7. Cells (5μl) carrying both plasmids at 5 x106 cells/ml were spotted onto -Leu-Trp dropout plates and -Leu-Trp-Ade-His  dropout plates to select for ADE2  and HIS3  markers. \"-\": Empty BD or AD plasmid.",
    "ncbi_link": "Bqt4: 2540694
Gal4: 855828
Rap1: 2540115
Taz1: 2542313"
  },
  {
    "caption": "(D) PFGE  analysis of nitrogen-starved bqt4∆ and bqt3∆ cells in the presence or absence of poz1.",
    "ncbi_link": "bqt3: 2539582
bqt4: 2540694
poz1: 2542244"
  },
  {
    "caption": "(E) End fusions in bqt4∆poz1∆ and bqt3∆poz1∆ are dependent on the presence of ligase IV. PFGE  analysis of nitrogen-starved cells in the presence or absence of lig4.",
    "ncbi_link": "bqt3: 2539582
bqt4: 2540694
lig4: 2539042
ligase IV: 2539042
poz1: 2542244"
  },
  {
    "caption": "B Representative western blots (upper) and analysis (lower) of the expression levels of Syb2 in control (Ctrl) and Syb2-cKO DRG neurons (n = 3 per group). Control DRG neurons is from homozygous floxed Syb2-null mice infected with AAV5-CAG-EGFP virus.",
    "ncbi_link": "EGFP: 
Syb2: 22318"
  },
  {
    "caption": "C Evoked EPSCs and statistics from DH neurons co-cultured with control (Ctrl) or Syb2-cKO DRG cells (cKO) in 0Ca2+ solution (n = 13 cells for Ctrl and 11 for cKO).",
    "ncbi_link": "Syb2: 22318"
  },
  {
    "caption": "F Left panels, evoked EPSCs from DH neurons co-cultured with scrambled shRNA control (Ctrl) or Cav2.2-KD (sh-1/sh-2) DRG neurons in 0Ca2+ solution. Right panel, quantification of evoked EPSCs (n = 17 cells for Ctrl, 12 for sh-1, and 19 for sh-2). EPSCs were evoked by local electrical stimulation (Estim, at arrows).",
    "ncbi_link": "Cav2.2: 257648"
  },
  {
    "caption": "(A) BACE1 internalization kinetics after 20 minutes (WT: 19.79±1.89%, KO: 13.28±1.57%, p WT vs KO=0.017) and 40 minutes of HA antibody chase (WT: 15.99±2.04, KO: 9.29±1.33, pWT vs KO=0.010) is significantly decreased in AP-2µ KO neurons (27 WT and 29 KO neurons). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(B) Representative examples of internalized BACE1 after 5 min of HA antibody pulse in HA-BACE1-eGFP-overexpressing WT and KO neurons. Scale bar: 5µm.",
    "ncbi_link": "BACE1: 
eGFP: 
HA: "
  },
  {
    "caption": "(C, D) Internalized BACE1 levels after 20 min of HA antibody pulse in HA-BACE1-eGFP-overexpressing WT and KO neurons, calculated as the HA (internalized)/eGFP (total) signal intensity ratio (WT: 0.50±0.052, KO: 0.23±0.036, p=0.000, 30 WT and 36 KO neurons, N=4 biological replicates). Scale bar: 5 µm. Data information: Experimental designs are depicted in the top panels where analyzed BACE1 fraction is marked with the red square. All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
HA: 
BACE1: 23621"
  },
  {
    "caption": "(E, F) Recycled BACE1 levels after 20 min of HA antibody pulse in HA-BACE1-eGFP-overexpressing WT and KO neurons, calculated as the HA(recycled)/eGFP(total) signal intensity ratio (WT: 0.29±0.031, KO: 0.53±0.040, p<000, 30 WT and 32 KO neurons, N=4 biological replicates). Scale bar: 5 µm. Data information: Experimental designs are depicted in the top panels where analyzed BACE1 fraction is marked with the red square. All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
HA: 
BACE1: 23621"
  },
  {
    "caption": "Recycled levels of BACE1 after 20 min of HA antibody pulse in HA-BACE1-mCherry-transfected WT and KO neurons, co-expressing either eGFP-RAB4 or eGFP-RAB4-S22N pWTRAB4 vs pWTRAB4S22N>0.999, 34-38 neurons, N=4 biological replicates). Scale bar: 5 µm. Data information: Experimental designs are depicted in the top panels , where analyzed BACE1 fraction is marked with the red square.",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
BACE1: 23621
RAB4: 5867"
  },
  {
    "caption": "Recycled levels of BACE1 after 20 min of HA antibody pulse in HA-BACE1-mCherry-transfected WT and KO neurons, co-expressing either eGFP-RAB4 or eGFP-RAB4-S22N, calculated as the HA(recycled)/mCherry(total) signal intensity ratio (WTRAB4: 0.14±0.02, KORAB4: 0.20±0.02, WTRAB4-S22N: 0.14±0.02, KORAB4S22N:0.14±0.01, pWTRAB4 vs pKORAB4=0.033, pKORAB4 vs pKORAB4S22N=0.035, pWTRABS22N vs pKORABS22N=0.999, pWTRAB4 vs pWTRAB4S22N>0.999, 34-38 neurons, N=4 biological replicates). Scale bar: 5 µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA in n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
RAB: 
BACE1: 23621
RAB4: 5867"
  },
  {
    "caption": "Recycled levels of BACE1 after 20 min of HA antibody chase in HA-BACE1-mCherry-transfected WT and KO neurons, co-expressing either eGFP-RAB11 or eGFP-RAB11-S22N, calculated as the HA(recycled)/mCherry(total) signal intensity ratio (WTRAB11: 0.11±0.01, KORAB11: 0.29±0.02, WTRAB11A-S25N: 0.14±0.02, KORAB11A-S25N: 0.19±0.02, pWTRAB11 vs pKORAB11<0.0001, pWTRAB11 vs pWTRAB11A-S25N=0.761, pKORAB11 vs pKORAB11A-S25N=0.001, pWTRAB11A-S25N vs pKORAB11A-S25N=0.175, 28-37 neurons per condition, N=3 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
BACE1: 23621
RAB11: 8766
RAB11A: 8766"
  },
  {
    "caption": "Internalized levels of BACE1 after 20 minutes of HA antibody uptake in HA-BACE1-mCherry transfected WT and KO neurons, co-expressing either eGFP-RAB4 or eGFP-RAB4-S22N pWTRAB4 vs pWTRAB4S22N=0.450, 27-37 neurons per condition, N=3 biological replicates). Scale bar: 5 µm. Data information: Experimental designs are depicted in the top panels where analyzed BACE1 fraction is marked with the red square.",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
BACE1: 23621
RAB4: 5867"
  },
  {
    "caption": "Internalized levels of BACE1 after 20 minutes of HA antibody uptake in HA-BACE1-mCherry transfected WT and KO neurons, co-expressing either eGFP-RAB4 or eGFP-RAB4-S22N, calculated as the HA(internalized)/mCherry(total) signal intensity ratio (WTRAB4: 0.54±0.05, KORAB4: 0.33±0.02, WTRAB4-S22N: 0.63±0.06, KORAB11A-S25N: 0.50±0.04, pWTRAB4 vs pKORAB4=0.004, pKORAB4 vs pKORAB4S22N=0.046, pWTRABS22N vs pKORABS22N=0.182, pWTRAB4 vs pWTRAB4S22N=0.450, 27-37 neurons per condition, N=3 biological replicates). Scale bar: 5 µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by ANOVA n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
RAB: 
BACE1: 23621
RAB4: 5867"
  },
  {
    "caption": "(L, M) BACE1 surface levels are increased in AP-2µ KO neurons, when compared to the WT set to 100% (KO: 129.65±5.30%, p=0.005, N=4 biological replicates). (N) Surface versus total BACE1 ratio is not altered in AP-2µ KO neurons when normalized to the WT set to 100% (KO: 83.02±10.93%, p=0.109, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test in (M,N). n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(A, B) BACE1 protein levels in cortical lysates of WT and AP-2µ KO mice. Protein levels in the KO were normalized to the WT set to 100% (KO: 447.64±48.78%, p<0.000, N=7 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(C, D) Immunofluorescence levels of BACE1 are significantly increased in the cortex of AP-2µ KO mice when normalized to the WT set to 100% (KO: 162.714±11.082%, p=0.005, N=4, biological replicates). Scale bar: 100µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(E) Localization of BACE1 in cultured WT and AP-2µ KO neurons. Scale bars: 20 µm, 5 µm (inserts).",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(K, L) Colocalization of BACE1 and RAB7A in cortical sections of WT and AP-2μ ΚΟ brains, quantified using Pearson's colocalization coefficient (WT: 0.18±0.04, KO: 0.35±0.05, p=0.038, N=4 biological replicates). Scale bar: 10 µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "(M Representative fluorescence images of WT neurons transfected with HA-BACE1-mCherry and immunostained for Cathepsin D. Channels were false color-coded to better illustrate the colocalization. Scale bars: 10µm. Arrowheads indicate BACE1 accumulation in lysosomes in the WT Dotted line outlines the neuron.",
    "ncbi_link": "HA: 
mCherry: 
BACE1: 23621"
  },
  {
    "caption": "N) Representative fluorescence images of AP-2µ KO neurons transfected with HA-BACE1-mCherry and immunostained for Cathepsin D. Channels were false color-coded to better illustrate the colocalization. Scale bars: 10µm. Arrowheads indicate BACE1 absence in the KO. Dotted line outlines the neuron.",
    "ncbi_link": "HA: 
mCherry: 
AP-2µ: 11773
BACE1: 23621"
  },
  {
    "caption": "(Q, R) Representative fluorescence images of WT and AP-2μ KO neurons transfected with BACE1-mKeima-Red and co-transfected with eBFP to reveal the neuronal morphology. Scale bars: 10µm, 2µm in zoomed images.",
    "ncbi_link": "eBFP: 
mKeima: 
AP-2μ: 11773
BACE1: 23621"
  },
  {
    "caption": "(A, B) Representative fluorescence images (A) and corresponding kymographs (B) from time-lapse videos of control neurons transfected with HA-BACE1-eGFP and co-transfected with AP-2μ-mCherry. Scale bars: (A) 2μm, 1.6µm inserts, (B) x=2μm, y=5s. Arrowheads in (A) correspond to BACE1 carriers indicated by the same arrowheads in (B).",
    "ncbi_link": "eGFP: 
HA: 
mCherry: 
AP-2μ: 116563
BACE1: 23621"
  },
  {
    "caption": "(C) Representative fluorescence images and corresponding kymographs from time-lapse videos of WT and AP-2μ KO neurons transfected with HA-BACE1-eGFP. Scale bar: 5µm top panels, x=2μm, y=5s bottom panels.",
    "ncbi_link": "eGFP: 
HA: 
AP-2μ: 11773
BACE1: 23621"
  },
  {
    "caption": "(D) Loss of AP-2μ significantly decreases the BACE1 motility (WT: 37.42±3.79%, KO: 23.07±3.07%, p=0.003, WT=31, KO=32 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "(E) Loss of AP-2μ significantly decreases the anterograde and retrograde BACE1 velocity (WTAntero: 0.37±0.02 μm/s, KOAntero: 0.22±0.03 μm/s, pWTAntero vs pKOAntero<0.000; WTRetro: 0.35±0.02 μm/s, KORetro: 0.25±.03 μm/s, pWTRetro vs pKORetro =0.006, WT=35 and KO=32 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "(F) Representative fluorescence images and corresponding kymographs from time-lapse videos of WT and AP-2μ KO neurons co-transfected with HA-BACE1-GFP and AP-2μ-mRFP. Scale bar: 5µm top panels, x=2μm, y=5s bottom panels.",
    "ncbi_link": "GFP: 
HA: 
mRFP: 
AP-2μ: 11773
AP-2μ: 116563
BACE1: 23621"
  },
  {
    "caption": "(G) Bi-directional mobility of BACE1 carriers in WT and AP-2μ ΚΟ neurons, co-expressing the AP-2μ-mRFP (WT: 37.60±2.20%, KO: 25.61±2.67%, WTAP-2μ-mRFP: 45.04±3.27%, KOAP-2μ-mRFP: 40.07±2.37%, pWT vs KO=0.005, pKO vs KO+AP-2μ-mRFP<0.000, pWT vs WT+AP-2μ-mRFP=0.186, pWT+AP-2μ-mRFP vs KO+AP-2μ-mRFP=0.570, 43-53 neurons per condition, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA in (G). n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "mRFP: 
AP-2μ: 11773
AP-2μ: 116563"
  },
  {
    "caption": "(H) Representative kymographs of WT and AP-2μ KO neurons co-expressing the HA-BACE1-GFP and tagRFP-LC3B. Scale bars: x=2μm, y=5s.",
    "ncbi_link": "GFP: 
HA: 
RFP: 
AP-2μ: 11773
BACE1: 23621
LC3B: 64862"
  },
  {
    "caption": "(I) Reduced bi-directional mobility of BACE1-containing autophagosomes in AP-2µ KO neurons. (WT: 33.53±4.19%, KO: 19.45±5.14%, p=0.000, WT=37 and KO=35 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(J) Representative kymographs of WT neurons co-expressing HA-BACE1-GFP and AP2-αΑ WT or AP2-αΑ Μut. Scale bar: 5µm top panels, x=2μm, y=5s bottom panels.",
    "ncbi_link": "GFP: 
HA: 
BACE1: 23621
AP2-α: 21418"
  },
  {
    "caption": "(K) Mobility of BACE1 carriers is significantly decreased in neurons overexpressing the AP2-αΑ Mut compared to neurons expressing the AP2-αΑ WT (WT: 52.23±4.16%, Mut: 27.95±3.31, p=<0.000, WT=26 and Mut=29 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP2-α: 21418"
  },
  {
    "caption": "(L) Representative fluorescence images and corresponding kymographs from time-lapse videos of WT neurons transfected with either HA-BACE1-GFP or HA-BACE1-LL/AA-GFP. Scale bar: 5µm top panels, x=2μm, y=5s bottom panels.",
    "ncbi_link": "GFP: 
GFP.: 
HA: 
BACE1: 23621"
  },
  {
    "caption": "(M) Reduced mobility of BACE1-LL/AA-positive vesicles, when compared to WT BACE1 (WT: 38.97±1.40%, LL/AA: 19.89±1.77%, p<0.000, WT=31 and LL/AA=33 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "BACE1: 23621"
  },
  {
    "caption": "(N) Reduced velocity of BACE1-LL/AA-positive vesicles, when compared to WT BACE1 (WTAntero: 0.38±0.03 μm/s, LL/AAAntero: 0.15±0.03 μm/s, pWTAntero vs pLL/AAAntero<0.000; WTRetro: 0.39±0.03 μm/s, LL/AARetro: 0.25±.03 μm/s, pWTRetro vs pLL/AARetro =0.000, WT=31 and LL/AA=33 neurons, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "BACE1: 23621"
  },
  {
    "caption": "(A, B) The eGFP/mCherry signal intensity ratio is significantly increased in mCherry-APP-P1-eGFP-expressing KO neurons comparing to the WT (WT: 0.94±0.06%, KO: 1.65±0.18, p=0.000, WT=39 and KO=41 neurons, N=5 biological replicates). Scale bars: 2μm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "eGFP: 
mCherry: 
APP: 351"
  },
  {
    "caption": "Confocal images of WT and AP-2μ ΚΟ entorhinal cortex immunostained with antibody recognizing total APP and APP-CTFs. Scale bars: 100 µm (C)",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "Confocal images of WT and AP-2μ ΚΟ entorhinal cortex immunostained with antibody recognizing total APP and APP-CTFs. Scale bars: 20µm (D).",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "(E-G) Levels of APP-CTFs are significantly increased in AP-2µ KO cortex compared to the WT set to 100% (KOC99: 156.65±8.37%, p=0.004, N=4 biological replicates; KOC83: 154.79±15.6%, p=0.012; N=5 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(H) Levels of full-length (FL) APP are unaltered in AP-2µ KO cortex (KOAPP FL: 106.64±12.96%, p=0.315, N=6 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(I) Levels of Nicastrin (NCT) are unaltered in the AP-2µ KO cortex",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(J, K) Intracellular levels of Aβ1-40 are significantly increased in AP-2µ KO axons compared to the WT (WTAβ1-40: 1.82±0.12, KOAβ1-40: 2.45±0.12, p=0.000, WT=24 and KO=24 neurons, N=3 biological replicates). Scale bars, 5µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "Intracellular levels of Aβ1-42 are significantly increased in AP-2µ KO axons (WTAβ1-42: 0.65±0.08, KOAβ1-42: 0.91±0.10, p=0.046, WT=38 and KO=38 neurons, N=3 biological replicates). Scale bar: 5 µm.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "Intracellular levels of Aβ1-42 are significantly increased in AP-2µ KO axons (WTAβ1-42: 0.65±0.08, KOAβ1-42: 0.91±0.10, p=0.046, WT=38 and KO=38 neurons, N=3 biological replicates). Scale bar: 5 µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(N) Significantly increased ratio of Αβ1-42/ Αβ1-40 measured by ELISA in the media of cultured AP-2μ KO neurons compared to the WT set to 100% (KO:124.57±10.97%, p=0.037, N=6 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2μ: 11773"
  },
  {
    "caption": "Accumulation of intracellular Aβ1−42 in neurons expressing the AP2-α−WT (WT: 1.14±0.18 , WT=28 and Mut=33 neurons, N=4 biological replicates). Scale bars: 20µm, 2µm (inserts).",
    "ncbi_link": "AP2-α: 21418"
  },
  {
    "caption": "Accumulation of intracellular Aβ1−42 in neurons overexpressing the AP2-α-Mut comparing to neurons expressing the AP2-α−WT (WT: 1.14±0.18, Mut: 2.06±0.29, p=0.011, WT=28 and Mut=33 neurons, N=4 biological replicates). Scale bars: 20µm, 2µm (inserts). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP2-α: 21418"
  },
  {
    "caption": "Accumulation of intracellular Aβ1-42 is rescued upon BACE1 knock-down (WTScr: 2.76±0.20 WTshBACE1: 2.52±0.12 27 to 39 neurons per condition, N=3 biological replicates). Scale bar: 10µm.",
    "ncbi_link": "BACE1: 23821"
  },
  {
    "caption": "Accumulation of intracellular Aβ1-42 is rescued upon BACE1 knock-down in AP-2µ KO neurons (WTScr: 2.76±0.20, KOScr: 3.94±0.21; WTshBACE1: 2.52±0.12; KOshBACE1: 2.74±0.21; pWTScr vs pKOScr=0.000, pKOscr vs pKOshBACE1=000; pWTscr vs pWTshBACE1=0.826; pWTshBACE1 vs pKOshBACE1=0.863; 27 to 39 neurons per condition, N=3 biological replicates). Scale bar: 10µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA in (T) n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773
BACE1: 23821"
  },
  {
    "caption": "(U, V) Levels of intracellular Aβ1−42 are significantly upregulated in neurons overexpressing the HA-BACE1-LL/AA-GFP comparing to neurons expressing the HA-BACE1-GFP (BACE1: 0.78±0.90, BACE1-LL-AA: 1.99±0.33, p=000, 28-29 neurons per condition, N=3 biological replicates). Scale bar, 50µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant. * indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "GFP: 
HA: 
BACE1: 23621"
  },
  {
    "caption": "(A, B) AP-2α levels normalized to GAPDH are significantly decreased in lysates of iPSC-derived neurons from late-onset AD patients carrying the TREM2 p.R47H (AD-TREM2-2 and AD-TREM2-4) variant compared to healthy controls (CON8 and CON9) set to 100% (ADAP-2α: 52.42±8.04%, p=0.020, N=3 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by one-sample Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "TREM2: 54209"
  },
  {
    "caption": "(C) Confocal images of either AP-2 WT (AAV-GFPCamkIIα-labelled) or AP-2 KO (AAV-Cre-GFPCamkIIα-labelled) granule neurons in the dentate gyrus of 13-week-old mice. Scale bars: 20µm, 2µm (inserts).",
    "ncbi_link": "GFP: 
AP-2: 11773
CamkIIα: 12322
Cre: 2777477"
  },
  {
    "caption": "(D) Loss of AP-2µ significantly decreases the number of spines on granule neurons (WT: 12.63±0.88, KO: 8.07±0.45, p=0.004, N=4 biological replicates). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(E, F) Overlap coefficient between the presynaptic marker Bassoon and the postsynaptic marker PSD95 is significantly decreased in the entorhinal cortex of AP-2µ KO mice compared to the WT (WT: 0.45±0.02, KO: 0.33±0.06, p=0.034, N=3 biological replicates). Scale bar, 750nm. Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "Lost preference for the novel object (nov) comparing to the familiar object (fam) in AP-2µ KO mice tested 24h after training in NOR Representative heatmaps are shown in (G).",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "Lost preference for the novel object (nov) comparing to the familiar object (fam) in AP-2µ KO mice tested 24h after training in NOR (WTfam: 27.51±6.77, WTnov: 72.49±6.77, pWTfam vs WTnov=0.000; KOfam: 43.9±13.12, KOnov: 59.91±13.12, pKOfam vs KOnov=0.469, N=7 WT and 8 KO mice). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(I, J) AP-2µ KO mice are significantly more active in the open field compared to the WT (WT: 1663±139.08%, KO: 3976±802.30%, p=0.020, N=7 WT and 8 KO mice). Representative heatmaps are shown in (I). Data information: All graphs show mean ± SEM, statistical analysis was performed by unpaired two-tailed Student's t‐test n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773"
  },
  {
    "caption": "(K, L) Overlap coefficient between Bassoon and PSD95 is rescued upon BACE1 KD in AP-2µ KO neurons (WTscr: 0.39±0.02; KOscr: 0.24±0.01; WTshBACE1: 0.37±0.02; KOshBACE1: 0.33±0.02; pWTscr vs pKOscr<0.000; pKOscr vs pKOshBACE1=0.010; pWTscr vs pWTshBACE1=0.813; pWTshBACE1 vs pKOshBACE1=0.623, 22-24 neurons for each condition, N=3). Scale bars: 10µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2µ: 11773
BACE1: 23821"
  },
  {
    "caption": "Neuronal loss is rescued in the entorhinal cortex of AP-2µ mice haploinsufficient for BACE1 (AP-2WT/BACEWT: 2.25±0.08 N=9 sections from N=3 for each genotype). Scale bar: 100 μm.",
    "ncbi_link": "AP-2: 11773
AP-2µ: 11773
BACE: 23821
BACE1: 23821"
  },
  {
    "caption": "Neuronal loss is rescued in the entorhinal cortex of AP-2µ KO mice haploinsufficient for BACE1 AP-2KO/BACEWT: 1.51±0.08, AP-2WT/BACEHET: 1.80±0.07, AP-2KO/BACEHET: 2.00±0.07; pAP-2WT/BACE1WT vs pAP-2KO/BACE1WT<0.000; pAP-2WT/BACE1WT vs pAP-2WT/BACE1HET=0.001; pAP-2KO/BACE1WT vs pAP-2KO/BACE1HET=0.000; p AP-2WT/BACE1HET vs AP-2KO/BACE1HET=0.268, N=9 sections from N=3 for each genotype). Scale bar: 100 μm. Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2: 11773
AP-2µ: 11773
BACE: 23821
BACE1: 23821"
  },
  {
    "caption": "(P, Q) APP-CTF levels are rescued in the entorhinal cortex of AP-2µ KO mice haploinsufficient for BACE1 (AP-2WT/BACEWT:427574±24021, AP-2KO/BACEWT: 538895±34662, AP-2WT/BACEHET: 389870±19842, AP-2KO/BACEHET: 395389±21853; pAP-2WT/BACE1WT vs pAP-2KO/BACE1WT=0.017; pAP-2KO/BACE1WT vs pAP-2KO/BACE1HET=0.001; p AP-2WT/BACE1HET vs AP-2KO/BACE1HET=0.979; 13-15 sections, N=3 mice for each genotype). Scale bars: 40µm. Data information: All graphs show mean ± SEM, statistical analysis was performed by two-way ANOVA n.s.-non-significant.* indicates p≤0.05, ** indicates p≤0.01, *** indicates p≤0.001.",
    "ncbi_link": "AP-2: 11773
AP-2µ: 11773
BACE: 23821
BACE1: 23821"
  },
  {
    "caption": "(A, B) Flies form well-organized compound eyes when they carry GMR-GAL4 without a target gene (A) but develop rough eyes when GMR-GAL4 drives expression of UAS-Foxn1 (B). Panel B shows the typical severity of the rough-eye phenotype. Data information: Representative phenotypes are shown in all panels. Scale bars, 100 μm.",
    "ncbi_link": "Foxn1: 15218
GAL4: 855828"
  },
  {
    "caption": "(C, D) Bristles are pigmented and properly shaped when flies carry hs-GAL4 without a target gene (C) but are often white, bent, and shortened when hs-GAL4 drives expression of UAS-Foxn1 (D). Flies in panels C and D were raised at 25°C. Arrows denote examples of white bristles. Data information: Representative phenotypes are shown in all panels. Scale bars, 100 μm.",
    "ncbi_link": "Foxn1: 15218
GAL4: 855828"
  },
  {
    "caption": "Representative skin phenotypes of Foxn1nu/nu (Nude), or KRT14-cre; Aff4flox/flox (Aff4 cko) mice are shown macroscopically or histologically after hematoxylin and eosin staining (H-N). The phenotypes compared are as follows: hair coats, 4-month-old adults; (E-G) vibrissae, P7; (H) hair follicles with growing hairs, juveniles; (I-K) regressing hair follicles, juveniles; (L-N) epidermis, P9. In panel H, micrographs from left to right are WT, Nude, and Aff4 cko. In panels I-K, HF marks examples of hair follicles. In panels L-M, arrowheads indicate the dermal/epidermal border; arrows mark examples of bent hair shafts. Scale bars: H, L-N, 20 µm; I-K, 40 µm.",
    "ncbi_link": "Aff4: 93736
cre: 2777477
Foxn1: 15218
KRT14: 16664"
  },
  {
    "caption": "(A-C) Thymi from E18.5 embryos are shown: (A) intact with genotypes indicated, or (B, C) after sectioning, immunofluorescent staining for DLL4 (red), and counterstaining of DNA (blue). Sectioned samples are wild-type (B) or Aff4ko/ko; Foxn1+/- (C). Scale bars: A, 1 mm; B-C, 50 µm.",
    "ncbi_link": "Aff4: 93736
Foxn1: 15218"
  },
  {
    "caption": "(C-E) KRT86 (red) is shown by immunofluorescence in skin sections from wild-type (WT), Foxn1 null, or Aff4 cko mice at P9. DNA is stained blue. HS marks examples of hair shafts. Scale bar, 40 µm.",
    "ncbi_link": "Aff4: 93736
Foxn1: 15218"
  },
  {
    "caption": "Graphs present pre-mRNA (B, C) assays of Krt86 using skin from mutant mice (Foxn1 null, Aff4 cko) or corresponding wild-type controls at P6 (B, C) All values are derived from 3 independent experiments and presented as mean ± S.D. Pre-mRNA measurements were analyzed statistically using two-way ANOVA with post-hoc Sidak's multiple comparison test at a 95% confidence interval.",
    "ncbi_link": "Aff4: 93736
Foxn1: 15218
Krt86: 16679"
  },
  {
    "caption": "Graphs present ChIP (D-G) assays of Krt86 using skin from mutant mice (Foxn1 null, Aff4 cko) or corresponding wild-type controls at P7 (D-G). ChIP assays were performed with antibodies to FOXN1 or AFF4 as indicated. All values are derived from 3 independent experiments and presented as mean ± S.D. ChIP assays were analyzed statistically using one-way ANOVA with post-hoc Tukey's multiple comparison test at a 95% confidence interval. ****, p ≤ 0.0001.",
    "ncbi_link": "Aff4: 93736
Foxn1: 15218
Krt86: 16679"
  },
  {
    "caption": "(B-G) Graphs present ChIP assays of Krt86 using antibodies to total (B, C), P-Ser5 (D, E), or P-Ser2 (F, G) Pol II and skin from mutant mice (Foxn1 null, Aff4 cko) or corresponding wild-type controls at P7. All values are derived from at least 3 independent experiments and presented as mean ± S.D. Assay results were analyzed statistically using one-way ANOVA with post-hoc Tukey's multiple comparison test at a 95% confidence interval. ****, p ≤ 0.0001.",
    "ncbi_link": "Aff4: 93736
Foxn1: 15218
Krt86: 16679"
  },
  {
    "caption": "A. qRT-PCR analysis of RNA samples from normal human skin (NS) and AK for activin βA (INHBA), normalized to hypoxanthine phosphoribosyltransferase (HPRT). Expression levels in one of the normal skin samples were set to 1. Scatter plots are shown. NS: N=4; AK: N=21. ns = non-significant (Mann-Whitney test).",
    "ncbi_link": "HPRT: 
INHBA: 3624"
  },
  {
    "caption": "B. qRT-PCR analysis of RNA samples from normal back skin of wild-type mice (N=4, n=4), non-tumorigenic back skin from HPV8/wt mice (N=7, n=9) and papillomas from HPV8/wt transgenic mice (N=8, n=11) for Inhba, normalized to glyceraldehyde 3-phosphate dehydrogenase (Gapdh). Expression levels in one of the wild-type back skin samples were set to 1. Statistical significance was determined using 1-way ANOVA and Bonferroni`s Multiple Comparisons Test of log-transformed data. N, number of mice; n, number of biopsies.",
    "ncbi_link": "Gapdh: 
Inhba: 16323"
  },
  {
    "caption": "F. Kinetics of tumor incidence in HPV8/wt and HPV8/Act mice; N=20 mice per genotype. Statistical significance was determined using Log-rank (Mantel-Cox) test.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "A,B. Representative pictures of ear sections from 10 week-old mice stained for δTcR (green); counterstained with Hoechst (blue) (A) and quantification of δTcR+ cells in the ear epidermis (B). Dotted lines indicate the epidermal-dermal border. Scale bar: 20μm. N=6 wt/wt mice, N=7 HPV8/wt mice, N=6 wt/Act mice and (N=8) HPV8/Act mice.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "C. Quantification of βTcR+ cells in ear skin cryosections from 10 week-old wt/wt (N=5); HPV8/wt (N=5); wt/Act (N=8) or HPV8/Act (N=8) mice.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "G. Representative pictures of ear cryosections from 10 week-old mice stained with antibodies against Foxp3 (red) and counterstained with Hoechst (blue). Insert shows higher magnification of the Foxp3-positive cells in wt/Act skin. Dotted lines indicate the epidermal-dermal border. Scale bar: 50μm.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "H. Kinetics of tumor incidence in HPV8/Act/wt (N=29), HPV8/Act/CD4KO (N=10), HPV8/wt/wt (N=23) and HPV8/wt/CD4KO (N=22) mice per genotype. Statistical significance was determined using the Log-rank (Mantel-Cox) test; ns = non-significant.",
    "ncbi_link": "CD4: 12504
Act: 16323"
  },
  {
    "caption": "A,B. Representative pictures of ear skin cryosections from 10-12 week-old mice stained with anti-CD206 antibodies (green); counterstained with Hoechst (blue) (A), and quantification of CD206+ area as a percentage of total dermal area (B) in wt/wt (N=3), HPV8/wt (N=7), wt/Act (N=2) or HPV8/Act (N=8) mice. The basement membrane is indicated with a white dotted line.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "D. Quantification of CD206+ area as a percentage of total dermal area in wt (N=7) and Act (N=6) mice in back skin treated 8x with TPA (Antsiferova et al, 2011).",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "E. Abundance of MerTK+CD64+ macrophages analyzed by flow cytometry of pre-tumorigenic ear skin from 12 week-old mice expressing the CCR2-CFP-DTR transgene (wt/CCR2) or double-transgenic animals (Act/CCR2), untreated or treated with diphtheria toxin (+DT) 3 times every 48h and analyzed 24h after the last injection. Percentage of CD45+CD11b+MerTK+CD64+ macrophages among live cells is shown. N=3 control wt/CCR2 and Act/CCR2 mice; N=4 DT-injected wt/CCR2 and Act/CCR2 mice. Representative flow cytometry scatter plots are shown in Appendix Fig S1E.",
    "ncbi_link": "CCR2: 12772
Act: 16323"
  },
  {
    "caption": "C. Differential expression of genes was analyzed using the edgeR software package. IPA was performed with filtered lists of up- and downregulated genes that exhibited an FDR-value of <0.1 in different genotype comparisons (wt/Act vs wt/wt; HPV8/Act vs HPV8/wt; HPV8/Act vs wt/wt). The number of differentially expressed genes used for analysis is indicated. Data are presented as pseudo-heatmap with magnitudes of Activation Z-scores color-coded as indicated in the legend; all non-grey comparisons are -log10(p-value)>2.5 unless otherwise indicated.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "D. Gene Set Enrichment Analysis (GSEA) was performed to compare transcriptomes of genotype comparisons (wt/Act vs wt/wt; HPV8/Act vs HPV8/wt; HPV8/Act vs wt/wt, [all]/Act vs [all]/wt) to 3 published datasets of Tumor-Associated Macrophages (TAM) (Franklin et al. 2014; Ojalvo et al, 2009; Galletti et al, 2016). Gene sets are composed of top genes upregulated (TAM UP) or downregulated (TAM DOWN) in TAM vs normal tissue macrophages. Positive Normalized Enrichment Score (NES) corresponds to enrichment of gene set in activin-upregulated genes; negative NES corresponds to enrichment in activin-downregulated genes. Data are presented as pseudo-heatmap with magnitudes of NES color-coded as indicated in the legend; all non-grey comparisons are FDR<0.10.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "E. Differential GSEA was performed on combined genotype comparison [all]/Act vs [all]/wt and two datasets of human AK vs normal skin (GSE2503; Nindl et al, 2006) and GSE63107 to compare these transcriptomes to gene sets derived from top upregulated genes in these datasets (top); and gene sets derived from top upregulated genes in datasets of differential human macrophage activation (IFN-γ, TNF-α, LPS, IL-4 vs non-treated) and selected human myeloid/lymphoid cell type-specific gene expression profiles (macrophage vs monocyte, dendritic cell, and T-cell) (Xue et al, 2014; bottom). Activin target genes enriched in the AK transcriptomes are shown (right). Data are presented as pseudo-heatmaps with magnitudes of Normalized Enrichment Scores (NES) and Log2(Fold Change) color-coded as indicated in the respective legends; all non-grey comparisons are FDR<0.05 for NES and p<0.10 for Fold Change.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "G. Heatmap of 28 differentially expressed genes (FDR≤0.05, |log2Ratio|≥1) overlapping in all 3 comparisons (wt/Act vs wt/wt mice, HPV8/Act vs HPV8/wt and HPV8/Act vs wt/wt). Genes with a published pro-tumorigenic function are highlighted in red.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "A,B,F. Expression of Cx3cr1 (A), Spp1 (B) relative to Rps29 was analyzed by qRT-PCR in peritoneal macrophages, resident or inflammatory, treated in vitro with 10 ng/ml of activin A (Act) or untreated (Ctrl, arbitrarily set to 1). Results are combined from 2-5 independent experiments performed with cells pooled from at least 5 wt mice.",
    "ncbi_link": "Rps29: 
Cx3cr1: 13051
Spp1: 20750"
  },
  {
    "caption": "E. Ear skin sections from 10 week-old mice stained with anti-CD68 (red) or anti-osteopontin antibody (green); counterstained with Hoechst (blue). Osteopontin-positive macrophages in wt/Act and HPV8/Act mice are indicated with arrows. Representative of N=2 wt/wt and N=3 HPV8/wt, wt/Act and HPV8/Act mice. Boxed areas in top panel are shown at higher magnification in bottom panel. Scale bar top: 100μm, bottom: 20μm.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "A,B,F. Expression of Arg1 (F) relative to Rps29 was analyzed by qRT-PCR in peritoneal macrophages, resident or inflammatory, treated in vitro with 10 ng/ml of activin A (Act) or untreated (Ctrl, arbitrarily set to 1). Results are combined from 2-5 independent experiments performed with cells pooled from at least 5 wt mice.",
    "ncbi_link": "Rps29: 
Arg1: 11846"
  },
  {
    "caption": "H,I. Gelatin zymography of ear skin lysates from 10 week-old mice. Inverted image of a representative gel with 2 (wt/wt) or 3 (HPV8/wt, wt/Act, HPV8/Act) mice per genotype is shown in (H), quantification of the results obtained in 2 independent experiments is shown in (I). N=5 wt/wt, N=6 HPV8/wt, wt/Act and HPV8/Act mice.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "A. Kinetics of tumor incidence in HPV8/Act mice treated for 5 weeks with 50mg/kg anti-CSF1R antibody (AFS98) or with control rat IgG. N=10 mice per treatment group.",
    "ncbi_link": "Act: 16323"
  },
  {
    "caption": "F. Expression of Mmp12 relative to Rps29 was analyzed by qRT-PCR in total ear skin from mice treated with anti-CSF1R antibody or with rat IgG. Expression in one of the IgG-injected mice was set to 1. N=10 per group.",
    "ncbi_link": "Rps29: 
Mmp12: 17381"
  },
  {
    "caption": "(A) Representative micrographs  of human skin  sections stained with hematoxylin-eosin (H&E) (left) and anti-IL-38 antibody (right) from normal patients  (n = 11) and tumors of cSCC patients  (n = 13). Scale bars represent 100 μm. The graph shows the quantification of mean  IL-38 expression   per high-powered field in tissues. (B) Relative expression   of  IL-38 in human  normal tissues (n = 9) and cSCC  (n = 18) were analyzed using Geo Datasets (GSE98767). Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test.",
    "ncbi_link": "IL-38: 84639"
  },
  {
    "caption": "(C and D) The  dorsal hair of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 32 weeks to induce skin  tumors. (C) Representative micrographs   of mouse normal skin  (n = 6) and tumor (n = 6) sections stained  with anti-IL-38  antibody. The graph shows the quantification of mean  IL-38 expression   per high-powered field in tissues. Scale bars represent 100 μm. (D) Relative expression   levels of Il-38 in normal skin  (n = 5) and tumors (n = 5) of mice  were quantified using qPCR. Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test.",
    "ncbi_link": "Il-38: 215274"
  },
  {
    "caption": "(B) Representative photographs  of Il-38f/f (n = 12) and K14Cre/+-Il-38f/f mice  (n = 8) treated with DMBA/TPA for 32 weeks. White triangles indicate the tumors  on the back of mice. (C Average tumor number (C) per mouse  from Il-38f/f (n = 12) and K14Cre/+-Il-38f/f mice  (n = 8) treated with DMBA/TPA.. Error bars represent the mean ± SD (C) All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test (C",
    "ncbi_link": "Cre: 2777477
Il-38: 215274
K14: 3861"
  },
  {
    "caption": "(A) Representative immunohistochemical staining micrographs  of γH2AX  in the skin  of Il-38f/f (n = 5) and   K14Cre/+-Il-38f/f (n = 5) mice  after treated with DMBA  for 24h. Red triangles indicate the γH2AX+ positive cells. Scale bars represent 100 μm. The graph shows the number of  γH2AX+ cells per high-powered field. Data information: Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test.",
    "ncbi_link": "Cre: 2777477
Il-38: 215274
K14: 3861"
  },
  {
    "caption": "(A The  dorsal hair  of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 3 weeks to induce the skin inflammation. (A) Representative micrograph  sections stained  with hematoxylin-eosin  (H&E) from the skin of Il-38f/f (n = 5) and  K14Cre/+-Il-38f/f mice (n = 5) Scale bars represent 100 μm. The graph shows average epidermal  thickness.",
    "ncbi_link": "Cre: 2777477
Il-38: 215274
K14: 3861"
  },
  {
    "caption": "B) The dorsal hair  of normal C57/BL6 mice  were shaved and treated with DMBA/TPA  twice a week for 3 weeks to induce the skin inflammation. (B) Representative micrograph  sections stained  with anti-Ki67  antibody from the skin  of Il-38f/f (n = 6) and K14Cre/+-Il-38f/f mice  (n = 6). Scale bars represent 100 μm. The graph shows average numbers of Ki67+ cells per high-powered field.",
    "ncbi_link": "Cre: 2777477
Il-38: 215274
K14: 3861"
  },
  {
    "caption": "(G and H) Representative images of the  scratch assay  (left) and  wound closure rate (right) of A431  cells (n = 5) after overexpression (G) or knockdown (H) of IL-38. Error bars represent the mean ± SD. All data are biological replicates. *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using Student's t test. NC, Negative control; LV, Lentivirus; Oe, Overexpression.",
    "ncbi_link": "IL-38: 84639"
  },
  {
    "caption": "(I and J) Representative  western blot  bands indicating cyclin E and cyclin A  in A431  cells after  IL-38 overexpression (I) or knockdown (J). NC, Negative control; LV, Lentivirus; Oe, Overexpression.",
    "ncbi_link": "IL-38: 84639"
  },
  {
    "caption": "(C) Cell extracts prepared from  293T  cells transfected with a mock mammalian expression vector (left) or an expression vector encoding  IL-1Rrp2 (right) were probed using anti-phospho-JNK, anti-JNK, or anti-β-actin antibodies after stimulation with IL-38 (200 ng/ml) or  IL-36β (200 ng/ml) at different times.",
    "ncbi_link": "IL-1Rrp2: 8808"
  },
  {
    "caption": "(D) Cell extracts prepared from 293T  cells transfected with an expression vector encoding IL-1Rrp2 were probed using anti-phospho-JNK, anti-JNK, or anti-β-actin antibodies after stimulation with IL-38 at different concentrations.",
    "ncbi_link": "IL-1Rrp2: 8808"
  },
  {
    "caption": "(F) Cell extracts prepared from 293T  cells transfected with HA-tagged full-length or deletion mutants of IL-1Rrp2, were probed using anti-HA  or anti-β-actin antibodies. Oe, overexpression.",
    "ncbi_link": "HA: 
IL-1Rrp2: 8808"
  },
  {
    "caption": "(G) Cell extracts prepared from 293T  cells transfected with full-length or deletion mutants of  IL-1Rrp2 were probed using anti-phospho-JNK, anti-JNK, or anti-β-actin antibodies after stimulation with  IL-38  (200 ng/ml) at different times.",
    "ncbi_link": "IL-1Rrp2: 8808"
  },
  {
    "caption": "Representative images of the scratch assay (left) and  wound closure rate (right) of A431  cells (n = 5) treated with recombinant  IL-38 (200 ng/mL) (F) after  IL-1Rrp2 interference. Error bars represent the mean ± SD. All data are biological replicates. ns, not significant; *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using one-way ANOVA , F",
    "ncbi_link": "IL-1Rrp2: 8808"
  },
  {
    "caption": "Representative images of the scratch assay (left) and  wound closure rate (right) of A431  cells (n = 5) treated with recombinant  IL-38 (200 ng/mL) (F) after JNK  interference. Error bars represent the mean ± SD. All data are biological replicates. ns, not significant; *p < 0.05; **p < 0.01; ***p < 0.001; p values were calculated using one-way ANOVA , F",
    "ncbi_link": "JNK: 5602///5601///5599"
  },
  {
    "caption": "Rag1-/-:Bcl2 and Art-/-:Bcl2 abl pre-B cells were treated with imatinib for 48 h to induce G1 arrest. (A) DSBs quantified by qPCR analysis of Igk (Jκ1) genomic DNA. Schematic shows germline (GL) Igk locus, unrepaired Jκ1 coding end (Cut) and primer location. Results are normalized to Rag1-/-:Bcl2 abl pre-B cells, which do not generate RAG DSBs and have only germline Igk DNA. Loss of Igk germline product is representative of DSB generation.",
    "ncbi_link": "abl: 11350
Art: 11604
Bcl2: 12043
Igk: 243469
Rag1: 19373"
  },
  {
    "caption": "Rag1-/-:Bcl2 and Art-/-:Bcl2 abl pre-B cells were treated with imatinib for 48 h to induce G1 arrest. (B) Representative images of 53BP1 foci. Scale bar denotes 8 μm. Bar graph shows percentage of cells with indicated number of foci from three biological replicates. In each replicate, 100 cells per condition were quantified.",
    "ncbi_link": "abl: 11350
Art: 11604
Bcl2: 12043
Rag1: 19373"
  },
  {
    "caption": "Rag1-/-:Bcl2 and Art-/-:Bcl2 abl pre-B cells were treated with imatinib for 48 h to induce G1 arrest. (C) Western blot analysis of KAP1 phosphorylation (p-KAP1), NF-κB2 (p100 and p52) and PIM2. GAPDH is shown as loading control.",
    "ncbi_link": "abl: 11350
Art: 11604
Bcl2: 12043
Rag1: 19373"
  },
  {
    "caption": "Rag1-/-:Bcl2 and Art-/-:Bcl2 abl pre-B cells were treated with imatinib for 48 h to induce G1 arrest. (D) Cd40 and Pim2 mRNA expression.",
    "ncbi_link": "abl: 11350
Art: 11604
Bcl2: 12043
Cd40: 21939
Pim2: 18715
Rag1: 19373"
  },
  {
    "caption": "Rag1-/-:Lig4-/-:Bcl2 abl pre-B cells were transduced with an empty vector (control) or vector expressing RAG1 then treated with imatinib for 48 h. (E) DSBs quantified by qPCR analysis of Igh (JH1) genomic DNA and analyzed as in A with results normalized to empty vector control, which has only germline Igh DNA.",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Igh: 111507
Lig4: 319583
Rag1: 19373
RAG1: 19373"
  },
  {
    "caption": "Rag1-/-:Lig4-/-:Bcl2 abl pre-B cells were transduced with an empty vector (control) or vector expressing RAG1 then treated with imatinib for 48 h. (F) Representative images of 53BP1 foci. Scale bar denotes 8 μm. Bar graph shows percentage of cells with indicated number of foci from three biological replicates. In each replicate, 100 cells per condition were quantified.",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Lig4: 319583
Rag1: 19373
RAG1: 19373"
  },
  {
    "caption": "E-H. Rag1-/-:Lig4-/-:Bcl2 abl pre-B cells were transduced with an empty vector (control) or vector expressing RAG1 then treated with imatinib for 48 h. (G) Western blot analysis of FLAG-RAG1, p-KAP1, NF-κB2, and PIM2. GAPDH is shown as loading control.",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Lig4: 319583
Rag1: 19373
RAG1: 19373"
  },
  {
    "caption": "Rag1-/-:Lig4-/-:Bcl2 abl pre-B cells were transduced with an empty vector (control) or vector expressing RAG1 then treated with imatinib for 48 h. (H) Cd40 and Pim2 mRNA expression.",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Cd40: 21939
Lig4: 319583
Pim2: 18715
Rag1: 19373
RAG1: 19373"
  },
  {
    "caption": "A. Rag1-/-:Lig4-/-:Bcl2:iCas9 abl pre-B cells were treated with (+) or without (-) 2 μM doxycycline (Dox) to induce Cas9 as indicated. Western blot shows FLAG-Cas9 and GAPDH (loading control).",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Cas9: 69900935
Lig4: 319583
Rag1: 19373"
  },
  {
    "caption": "Rag1-/-:Lig4-/-:Bcl2:iCas9 abl pre-B cells were treated with doxycycline as in A and imatinib to trigger cell cycle arrest for 24 h. Cells were then transfected with indicated gRNA and maintained in doxycycline and imatinib. All analyses were completed 48 h after gRNA transfection. DSBs quantified by qPCR analysis of Eb (B) and Gapdh (C) genomic DNA. Results are normalized to cells without gRNA (-). Schematic shows germline (GL) locus, unrepaired cut end (Cut) and location of gRNA and primers. Loss of germline product is representative of DSB generation.",
    "ncbi_link": "abl: 11350
Bcl2: 12043
Cas9: 69900935
Gapdh: 14433
Lig4: 319583
Rag1: 19373
Eb: 21425"
  },
  {
    "caption": "(E) Western blot analysis of FLAG-tagged Cas9 or RAG1 (as indicated), p-KAP1, NF-κB2, and PIM2. GAPDH is shown as loading control. Responses to RAG DSBs in Rag1-/-:Lig4-/-:Bcl2 abl pre-B cells transduced with empty vector or vector expressing RAG1 RAG DSBs from Fig 1G are included for direct comparison. # denotes band for FLAG-Cas9. * denotes band for FLAG-RAG1.",
    "ncbi_link": "FLAG: 
abl: 11350
Bcl2: 12043
Lig4: 319583
RAG1: 19373
Rag1: 19373"
  },
  {
    "caption": "(F) Cd40 and Pim2 mRNA expression. Blue dashed line indicates mRNA expression in response to RAG DSBs from Fig 1H and is included for comparison.",
    "ncbi_link": "Cd40: 21939
Pim2: 18715"
  },
  {
    "caption": "E. CD40 and Pim2 mRNA expression. Blue dashed line indicates mRNA expression in response to RAG DSBs from Fig 1H and is included for comparison.",
    "ncbi_link": "CD40: 21939
Pim2: 18715"
  },
  {
    "caption": "B. DSBs quantified by qPCR analysis of Igh (JH1) genomic DNA and analyzed as in Fig 1E with results normalized to empty vector control, which has only germline Igh DNA. There is no statistically significant difference in DSBs generated by cRAG1 or RAG1P326G compared to full-length RAG1.",
    "ncbi_link": "Igh: 111507
RAG1: 19373"
  },
  {
    "caption": "E. Cd40 and Pim2 mRNA expression.",
    "ncbi_link": "Cd40: 21939
Pim2: 18715"
  },
  {
    "caption": "A Sting-/- iBMDMs expressing mRuby3-STING (magenta) and eGFP-Golgin84 (green) were imaged live on the 3i marianas spinning disk microscope. Z stack images were acquired either before (i.e., untreated) or after 50 μg/mL DMXAA treatment (i.e., image captured at 12 min post DMXAA treatment). Data is shown as a maximum intensity projection (MIP) of Z stack images.",
    "ncbi_link": "Sting: 72512"
  },
  {
    "caption": "D Sting-/- iBMDMs expressing mRuby3-STING were imaged live on the spinning disk microscope. Representative images of timelapse showing STING vesicles exiting the Golgi for a recording starting 27 min after 50 μg/mL DMXAA treatment. Data is shown as a MIP of Z stack images. Square region of interest (ROI) indicates zoomed insert. Scale bar = 5 μm.",
    "ncbi_link": "Sting: 72512"
  },
  {
    "caption": "F Sting-/- iBMDMs expressing eGFP-STING were imaged live on the spinning disk microscope. A representative image of timelapse showing transport of STING vesicles for a recording starting 1 h 18 min after 50 μg/mL DMXAA treatment. Data is shown as a MIP of Z stack images. Square ROI indicates zoomed insert. Scale bar = 5 μm.",
    "ncbi_link": "Sting: 72512"
  },
  {
    "caption": "D Sting-/-, WT or TBK1/IKKε dKO iBMDMs were left untreated or treated with 10 μg/mL 2'3'-cGAM(PS)2 for 1, 2, or 3 h. Cells were lysed for immunoblot with the indicated antibodies. Data shown representative of 3 independent experiments.",
    "ncbi_link": "IKKε: 56489
Sting: 72512
TBK1: 56480"
  },
  {
    "caption": "G-I Primary BMDMs were treated with 2 μM TAK243 or DMSO vehicle control for 30 min before being either left untreated (UT) or treated with 25 μg/mL DMXAA or 10 μg/mL 2'3'-cGAM(PS)2 for 4 h. Cells were lysed for RNA purification and the expression of Ifnb1 (G) , Isg15 (H) and Il6 (I) was analysed by qPCR. Data is shown as mean ± SEM combined from N=3 independent experiments. Statistical analysis was performed using two-way ANOVA using Bonferroni's multiple comparisons test, where * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.",
    "ncbi_link": "Ifnb1: 15977
Il6: 16193
Isg15: 100038882"
  },
  {
    "caption": "B Sting-/- iBMDMs expressing HA-STING were left UT or treated with 50 μg/mL DMXAA for 1 or 3 h. Cells were lysed and a portion of lysate underwent immunoblot with the indicated antibodies (i.e., lysate). The remaining lysate underwent immunoprecipitation with an anti-HA antibody (i.e., HA pull down). Samples then underwent immunoblot with the indicated antibodies. Data representative of 3 independent experiments.",
    "ncbi_link": "HA: 
Sting: 72512
STING: 72512"
  },
  {
    "caption": "A dCas9-KRAB expressing iBMDMs, without (i.e., dCas9 alone) or with HRS-targeting sgRNAs (i.e., sg1, sg2 or sg3) were treated for 48 h with 1 μg/mL doxycycline (Dox) to induce sgRNA expression. Cells were then left untreated (UT), or treated with 20 μg/mL DMXAA or 10 μg/mL 2'3'-cGAM(PS)2 for 6 h. Cells were lysed for immunoblot with the indicated antibodies. Data shown is representative of 3 independent experiments.",
    "ncbi_link": "Cas9: 69900935
HRS: 15239"
  },
  {
    "caption": "B-C dCas9-KRAB expressing iBMDMs, without (i.e., dCas9 alone) or with HRS-targeting sgRNAs (i.e., sg1, sg2 or sg3) were treated for 48 h with 1 μg/mL Dox to induce sgRNA expression. Cells were then left UT, or treated with 20 μg/mL DMXAA or 5 μg/mL 2'3'-cGAM(PS)2 for 6 h. Cell supernatant was collected and assayed for secreted IFNβ (B) and IL6 (C) by ELISA. Data is shown as mean ± SEM combined from N=3 independent experiments. Statistical analysis was performed using two-way ANOVA using Bonferroni's test, where * p<0.05, *** p<0.001, **** p<0.0001. n.d. = not detected",
    "ncbi_link": "Cas9: 69900935
HRS: 15239"
  },
  {
    "caption": "D-F dCas9-KRAB expressing iBMDMs, without (i.e., dCas9 alone) or with HRS-targeting sgRNAs (i.e., sg1, sg2 or sg3) were treated for 24 h with 1 μg/mL Dox to induce sgRNA expression. iBMDMs were further treated with 1 μg/mL (i.e. 1000 ng/mL) or 100 ng/mL H-151 as indicated, and incubated for a further 24 h. Cells were lysed for RNA purification and the expression of Ifnb1 (D), Isg15 (E) and Irf7 (F) was analysed by qPCR. Data is shown as mean ± SEM combined from N=3 independent experiments. Statistical analysis was performed using two-way ANOVA using Tukey's multiple comparisons test, where * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Bars display significant differences between dCas9 and sgRNA knockdowns in the absence of H-151. Additional asterisks represent significant differences between the absence or presence of H-151 across the same cell line.",
    "ncbi_link": "Cas9: 69900935
HRS: 15239
Ifnb1: 15977
Irf7: 54123
Isg15: 100038882"
  },
  {
    "caption": "A-B VPS4aWT or VPS4aE228Q dominant negative BMDMs were left untreated (UT) or treated with 1 μg/mL doxycycline (Dox) for 4 h. BMDMs were then further left UT or treated with 25 μg/mL DMXAA (A) or 10 μg/mL 2'3'-cGAM(PS)2 (B) for 4 h. Cells were lysed for immunoblot with the indicated antibodies. Data shown is representative of 2 independent experiments for A and 3 independent experiments for B.",
    "ncbi_link": "VPS4a: 27183"
  },
  {
    "caption": "C-D VPS4aWT or VPS4aE228Q dominant negative BMDMs were left UT or treated with 1 μg/mL Dox for 4 h. BMDMs were then further left UT or treated with 25 μg/mL DMXAA for 4 h. Cell supernatant was collected and secreted IFNβ (C) or IL-6 (D) was measured by ELISA. Data is shown as mean ± SEM combined from N=3 independent experiments. Statistical analysis was performed using one-way ANOVA. using Bonferroni's test, where * p<0.01. n.d. = not detected",
    "ncbi_link": "VPS4a: 27183"
  },
  {
    "caption": "ChIP analysis of young (PD 30) and senescent (PD 72) MRC-5 cells performed with either anti-RAP1, anti-TRF2 or an IgG antibody. The immunoprecipitated and input products were loaded into a slot blot membrane and hybridized with a telomere probe, stripped and hybridized to an Alu probe in order to determine unspecific binding. Quantification was performed by normalizing the telomere signal of the immunoprecipitated to that of the input. Data represent mean +/- SD of three biological replicates.",
    "ncbi_link": "Alu: "
  },
  {
    "caption": "Number of telomere fusions performed by PCR using 3 subtelomeric primers in the same reaction (16p1, 21q1 and XpYpM). The primer 16p1 is able to bind the subtelomeric region of 1p 9q, 12p, 15q, 16p, XqYq and the interstitial 2q14 region; the 21q1 primer binds the subtelomeric region of 1q, 2q, 5q, 6q, 6p, 8p, 10q, 13q, 19p, 19q, 21q, 22q and the interstitial 2q13 site. The PCR-fusion assay was performed in MRC-5 primary fibroblasts of different population doublings (PD) with or without depletion of RAP1 (shRAP1 or shControl respectively). Lentiviral infection was performed for 10 days. Data represent mean +/- SD of 3 biological replicates. Statistical analyses were performed using Mann-Whitney U test (**p < 0.001; ***p < 0.0001). Southern blotting showing the hybridization of the 16p probe for the conditions described in A. Number of fusions per 1 µg of DNA is shown at the bottom of the gels.",
    "ncbi_link": "RAP1: 54386"
  },
  {
    "caption": "Distribution of the telomere repeat array found at the junction between two fused chromosomes of senescent cells transduced with lentiviral vectors expressing either shControl or shRAP1. Variant telomere repeats were included in the estimation of the telomere array length. Data represent median +/- interquartile range (green lines) of 3 biological replicates. Statistical analysis was performed using Mann-Whitney U test ***p < 0.0001).",
    "ncbi_link": "RAP1: 54386"
  },
  {
    "caption": "Number of fusions in HeLa cells after 25 days in culture. Cells were maintained with BIBR1532 during the whole period of the experiment, while doxycycline (1 µg/µl final concentration) and the infection with shControl, shLIG3 or shLIG4 was carried out for the last 15 days of the experiment. Data represent mean +/- SD of three biological replicates are shown. Statistical analyses were performed using Mann-Whitney U test (*p < 0.05; **p < 0.001; ***p < 0.0001).",
    "ncbi_link": "LIG3: 3980
LIG4: 3981"
  },
  {
    "caption": "Growth curve of MRC-5 fibroblasts. Cells were grown until senescence and after three weeks of no growth detection, lentiviral infections containing either shp21CIP1 or shp21CIP1 + shRAP1 sequences were performed. Cells were harvested 15 days post infection (dpi). Data represent mean +/- SD of three biological replicates measured after 8 and 15 dpi.",
    "ncbi_link": "p21CIP1: 1026
RAP1: 54386"
  },
  {
    "caption": "Expression of p21CIP1 and RAP1 after 15 dpi of cells transduced with shControl, shp21CIP1 or shp21CIP1 + shRAP1.",
    "ncbi_link": "p21CIP1: 1026
RAP1: 54386"
  },
  {
    "caption": "Senescent cells, transduced with shp21CIP1 or shp21CIP1+shRAP1 for 15 days, were stained with CytoCalcein violet (live cells), Apopxin Green (apoptotic cells) and 7-aminoactinomycin D (7-AAD) (late apoptostic/necrotic cells) and visualized by flow cytometry. Quantification of apoptotic cells from the conditions described in E. Data represent mean +/- SD of three biological replicates (**P < 0.001; two-tailed Student's t test).",
    "ncbi_link": "p21CIP1: 1026
RAP1: 54386"
  },
  {
    "caption": "Isolated sporozoites from the hemolymph (HL) and salivary glands (SG) of infected mosquitoes stained with Hoechst and SiR-tubulin. Note the similar staining of WT and α1-tubulin(-) complemented lines. Scale bars: 5 µm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "Comparison of sporozoite development in oocysts of WT, α1-tubulin(-) and complemented lines. Hoechst (blue) and SiR-tubulin (green) staining reveal that the complemented line generates sporozoites indistinguishable from WT controls, while SiR tubulin staining is absent from α1-tubulin(-) oocysts. mCherry stains the cytoplasm of the parasite. Scale bars: 5 µm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "Transmission electron micrographs of developing sporozoites in WT and α1-tubulin(-) parasite lines. Note the slender sporozoites in the WT oocysts, which are absent in the mutant. Sb: sporoblast; scale bars: 5 µm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "TEM cross sections of WT and α1-tubulin(-) parasites showing the aberrant structure of the latter. Subpellicular and centriolar plaque (spindle pole body) associated (hemispindle) microtubules are readily recognizable in the WT sporozoites (green arrowheads in insert) but absent in the mutant, while the inner membrane complex is formed below the plasma membrane of both parasites (white arrowheads). Note the different scale chosen to highlight the malformed shapes in the mutant. N: nucleus; scale bars: 0.2 µm, magnification boxes: 0.1 µm,.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "Electron micrographs showing different stages of development in WT and α1-tubulin(-) parasites. Key structural elements are highlighted in the following colors: blue: plasma membrane; yellow: inner membrane complex; green: microtubules; light blue: micronemes; lilac: rhoptries; brown: rootlet fiber; cyan: nucleus. Note the undulating shapes of the elongated mutants and that micronemes are hard to distinguish from other small vesicles in the α1-tubulin(-) parasites. The rootlet fiber in panel II starts at the apical tip and in panel V is associated with the centriolar plaque (dark structure in nuclear envelope). Panel III corresponds to Fig 1D. Scale bars: 200 nm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "α1-tubulin(-) parasites show multiple attachments (arrowheads) with the sporoblast membrane at day 17 post infection. Note the highly branched nature of the budding parasite (same parasite as in panel C) shown in two views in I and II. Right: slices through the tomogram in grey scale with the outlines used for the 3D model indicated. Two connections with the sporoblast are indicated by 1 and 2. Scale bars: 1 µm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "Life imaging of wild-type (WT) and α1-tubulin(-) oocysts expressing ef1α:GFP (early and late oocysts) and csp:mCherry (late oocysts) to locate the oocyst cytoplasm. Microtubules were labeled with SiR-tubulin (green) and DNA with Hoechst (blue). Oocysts are shown in a chronological order from early (day 4) to late (day 12) development. (A, B) Early oocyst development with remaining subpellicular microtubules of the preceding ookinete stage (A) and subsequent DNA replication (B), where some but not all DNA is co-stained by microtubules in the mutant. (C) Nuclear alignments to the invaginated plasma membrane and budding of sporozoites. Note the strong SiR-tubulin signal only seen in sporozoites of WT oocysts and complete absence from the mutant. Sb: sporoblast. (D) Oocyst ready to burst with fully formed sporozoites in WT oocysts. Note that α1-tubulin(-) oocysts retained sporozoite nuclei predominantly within the sporoblast (Sb) during budding. Scale bars: 5 μm, magnification box in B: 1 µm,.",
    "ncbi_link": "GFP: 
mCherry: 
csp: 3428738
α1-tubulin: 3424816
ef1α: 3426474"
  },
  {
    "caption": "3D reconstructions from spinning disc confocal microscopy z-stacks across an early oocyst labelled with the DNA dye Hoechst (left). 50 and 19 images with a z-distance of 0.5 µm and 1 µm were collated for WT and α1-tubulin(-) oocysts, respectively. Right: 3D reconstructions from late WT and α1-tubulin(-) oocysts labelled with Hoechst (blue) and SiR-tubulin (green). Note that the mutant does not form proper sporozoite shapes during budding and the few peripheral nuclei that were uptaken into budding sporozoites. 10 and 28 images with a z-distance of 1,5 µm and 1 µm were collated for WT and α1-tubulin(-) oocysts, respectively. Sb: sporoblast; scale bars: 5 µm.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "TEM cross sections of WT and α1-tubulin(-) oocysts during nuclear division. Spindle microtubules (arrowheads) emerging from centriolar plaques (M) were seen in WT oocysts. Although individual nuclei (N) were visible in α1(-) oocysts, microtubules were absent even in dividing centriolar plaques (M). Scale bars: 0.2 μm.",
    "ncbi_link": "α1: 3424816
α1-tubulin: 3424816"
  },
  {
    "caption": "Fluorescence images showing the SiR-tubulin stained microtubules, nuclei (Hoechst) and cytoplasmic shape (mCherry) of the parasite lines. Note the small amount of DNA (black arrowhead) and the reduced level of SiR-tubulin fluorescence in the α1cm&∆introns-expressing sporozoites (lower graph). See also Fig S6. Quantitative data was derived from 96-120 sporozoites per line. Box plots represent 50% (boxes) and 95% (bars) of data with horizontal bar showing the median. Scale bar: 5 μm. **** indicates p<0.0001, Kruskal-Wallis-test. Note that α1cm&∆introns-expressing sporozoites do not express mCherry; their autofluorescence (auto-fluo) indicates an aberrant shape.",
    "ncbi_link": "mCherry: 
α1: 3424816"
  },
  {
    "caption": "TEM reveals α1cm&∆introns-expressing sporozoites with smaller (A and B) and larger (C) diameters than wild type sporozoites. See also Fig S7. Scale bar: 0.2 µm.",
    "ncbi_link": "α1: 3424816"
  },
  {
    "caption": "α1cm&∆introns-expressing sporozoites show a reduced number of subpellicular microtubules (green arrowheads) by TEM.",
    "ncbi_link": "α1: 3424816"
  },
  {
    "caption": "Expression of different α1-α2 chimeric α-tubulins instead of α1-tubulin leads to sporozoite shape changes as revealed by SEM. See also Fig EV5. Scale bar: 1 µm. α1∆c-term lacks the last 3 amino acids of α1-tubulin. α2+ parasites contain an α1-tubulin with all amino acids that are different between the two α-tubulins changed into those of α2-tubulin; see also Fig S4. α2++ parasites contain α2-tubulin (exons, introns, 3'UTR) and α2+++ parasites express the exons of α2-tubulin and introns of α1-tubulin from the α1-tubulin promoter.",
    "ncbi_link": "α1-tubulin: 3424816
α-tubulins: 3424816
α1: 3424816
α2-tubulin: 3421492
α2: 3421492"
  },
  {
    "caption": "qRT-PCR analysis of the parasite lines at day 12 after infection shows different expression level. Note the subtly higher expression of α2++ compared to α2+++. Error bars show standard deviation from the mean of two biological replicates.",
    "ncbi_link": "α2: 3421492"
  },
  {
    "caption": "TEM along sporozoites shows a decrease of microtubule numbers towards the nucleus in parasites expressing α-tubulin chimeras. Green arrowheads point to microtubules. See also Fig S8 and S9. Note that the WT control panel is shown already in Figure 4E to indicate that here we perform an extended analysis to the dataset generated earlier. Scale bars: 0.2 µm.",
    "ncbi_link": "α-tubulin: 3424816"
  },
  {
    "caption": "Microtubule quantification along the sporozoite reveals the presence of fewer microtubules in central and nuclear sections of α2+ and α1∆c-term parasites compared to wild type sporozoites.",
    "ncbi_link": "α1: 3424816
α2: 3421492"
  },
  {
    "caption": "The average microtubule length remains close to the maximum length 6 μm. The circles are obtained by averaging results from 200 stochastic simulations of the model equations and stars are the experimental data (blue stars are for (α2+, α2++, α2+++) strains). The error bar shows the standard deviation in the data and simulation results.",
    "ncbi_link": "α2: 3421492"
  },
  {
    "caption": "For the WT expression level (c0 = 36.6 (m0+p+n)), the rate of nucleation is faster than the microtubule growth. Then the microtubule number is determined by the number of nucleation sites. The average microtubule length is around 1 μm (shown by dashed arrow) when the last nucleus forms. At intermediate tubulin numbers (c0 = 16 (m0+p+n)), corresponding to the α1c-term mutant, the microtubule formation rate is comparable to nucleation rate. The average microtubule length is around 4 μm (shown by dashed arrow) when the last nucleus forms.",
    "ncbi_link": "α1: 3424816"
  },
  {
    "caption": "Quantification of SiR-tubulin fluorescence from 69-127 salivary gland derived sporozoites. Note the decrease in the fluorescence intensity of sporozoites expressing α1-tubulin without introns as well as the decreased intensity and length of the chimeras. Linear correlation of sporozoite length and microtubule length reveals a R2=0.94. *, **, and **** indicate p<0.05, p<0.01, and p<0.0001, respectively; ns: not significant; Kruskal-Wallis-test.",
    "ncbi_link": "α1-tubulin: 3424816"
  },
  {
    "caption": "Sporozoites with fewest microtubules (α2+++) show a motility defect. n indicates numbers of investigated sporozoites; Numbers on grey bars indicate percentage of partially and persistently moving sporozoites.",
    "ncbi_link": "α2: 3421492"
  },
  {
    "caption": "Salivary gland sporozoites contain at least 10 microtubules as revealed by TEM of α2++ infected salivary glands. Green arrowheads point to microtubules. Scale bar: 0.2 µm. Error bars show the full range and boxes 50% of values. Red crosses indicate the mean, red lines the median. Fisher's exact test (two-tailed).",
    "ncbi_link": "α2: 3421492"
  },
  {
    "caption": "MDM were transduced with non-specific scrambled shRNA (shNS) or Beclin-1 shRNA (shBCLN1) and selected using puromycin resistance. Five days later, cells were incubated with 100 pmol/L 1,25D3 or vehicle control for 4 h before infection with HIV and/or M. tuberculosis (TB) for 3 h. Cells were then washed and incubated with 100 pmol/L 1,25D3 or vehicle control for 7 days. (A) Immunoblot analysis performed using antibodies raised to Beclin-1 or β-actin after initial pathogen exposure (Day 0) or after 7 days.",
    "ncbi_link": "Beclin-1: 8678"
  },
  {
    "caption": "Inhibition of HIV and M. tuberculosis by 1,25D3 is CAMP and autophagy dependent.MDM were transduced with non-specific scrambled shRNA (shNS) or CAMP shRNA (shCAMP) and selected using puromycin resistance. Five days later, cells were incubated with 100 pmol/L 1,25D3 or vehicle control for 4 h before infection with HIV and/or M. tuberculosis (TB) for 3 h. Cells were then washed and incubated with 100 pmol/L 1,25D3 or vehicle control for 7 days. (A) Immunoblot analysis performed using antibodies raised to CAMP or β-actin after initial pathogen exposure (Day 0) or after 7 days.",
    "ncbi_link": "CAMP: 820"
  },
  {
    "caption": "(C-D) Snapshots from confocal live imaging movies of a representative embryo (N=7) during cellularisation co-expressing opto-Notch, Mito-Zdk, MCP::GFP and sim-MS2. Continuous photo-activation from the onset of cellularisation with a stack size of z= 25μm (λ=488 nm) was alternated with mCherry excitation (λ=561 nm) at 1 min intervals. Single confocal z-slices of the mCherry channel are shown to record opto-Notch localization before, and 10 minutes after sustained photo-activation. Magnified insets show opto-Notch bound to the mitochondrial anchor in the dark (C) and in the nucleus upon photo-activation (D). Scale bar, 10 μm.",
    "ncbi_link": "GFP: 
MCP: 
MS2: 
Zdk: 
Notch: 31293
sim: 41612"
  },
  {
    "caption": "(D-E) Results of continuous activation experiments in a Hairless heterozygous hypomorphic mutant (Hairless H2) and under overexpression of Twist (Twist OE) The observed outcomes are most consistent with the predictions from the state-dependent inactivation model.",
    "ncbi_link": "Hairless: 42445
Twist: 37655"
  },
  {
    "caption": "In situ hybridization of HAND2-AS1 in HCC tumor tissues. HAND2-AS1 staining is shown in tumor tissues (left panel). Quantitation of HAND2-AS1+ cells in liver tissues was examined in 10 high-power fields (HPF) of sections from ten different HCC patients (right panel). Results are shown as means ± SEM. Scale bar, 100 μm.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Macroscopic appearance of livers in 12-month-old DEN-treated lncHand2+/+ and lncHand2 knockout (lncHand2-/-) mice (left panel). Black arrows indicate liver tumors. Quantitation of tumor foci numbers and areas in DEN-treated livers (right panel). Results are shown as means ± SD (n=12).",
    "ncbi_link": "Hand2: 15111"
  },
  {
    "caption": "Representative H&E and immunohistological staining with Ki67 antibody of liver sections of 12-month-old DEN-treated lncHand2+/+ and lncHand2-/- mice. Scale bar, 100 μm.",
    "ncbi_link": "Hand2: 15111"
  },
  {
    "caption": "Representative immunofluorescence staining of livers in 5.5-month-old DEN-treated and untreated lncHand2RFP reporter mice for indicated molecules (lower panel). Scale bar, 100 μm. Upper panel: scheme of targeting strategy for IRES-RFP knockin allele.",
    "ncbi_link": "RFP: 
Hand2: 15111"
  },
  {
    "caption": "HAND2-AS1 knockout causes a declined oncosphere-forming capacity in HCC cells. The right panel represents statistical results as means ± SD (n=3 per group). Overexpression of HAND2-AS1 (oelnc) rescued the sphere formation reduced by HAND2-AS1 deletion. Scale bar, 100 μm.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "CD13+CD133+ (CSC) subpopulations were detected in HAND2-AS1 knockout cells by FACS analysis. Results are shown as means ± SD (n=4 per group).",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Limiting diluted HAND2-AS1 depletion or Ctrl HCC cells were subcutaneously implanted into BALB/c nude mice. n=12 for each group.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 deficiency and control cells after the first transplantation using the extreme limiting dilution analysis. Data are shown as the mean and 95% confidence interval. (n=12 grafted tumors per dilution).",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 deficiency and control HCC cells during serial transplantations. Grey area indicates the 95% CI.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 deficiency and control HCC cells during serial transplantations. Grey area indicates the 95% CI.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Representative whole-body imaging of Huh7-Luc cells transduced with control or HAND2-AS1 KO #1 or KO #2 vectors. Quantification of tumor numbers of 6 weeks after tumor cells orthotopically implanted to B-NSG mice. Data are shown as means ± SD. One-way ANOVA with Dunnett's correction for multiple comparisons.",
    "ncbi_link": "Luc: 
HAND2-AS1: 79804"
  },
  {
    "caption": "HAND2-AS1 expression levels (normalized to 18S rRNA) in livers from BALB/c nude mice subcutaneously transplanted xenograft primary HCC cells then intraperitoneally administered 25 mg kg−1 ASOs on days 15, 20, 25, 30 and 35 (n = 5 per group). Three ASOs (1, 2, 3) against HAND2-AS1 were used to treat mice and showed similar depletion effects. Results are shown as means ± SD. n=6 mice per group.",
    "ncbi_link": "18S rRNA: 
HAND2-AS1: 79804"
  },
  {
    "caption": "HAND2-AS1 overexpression enhances the capacity of oncosphere formation. Scale bar, 100 μm. oe: overexpression. Right panel: Data are shown as means ± SD (n = 3 per group).",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Estimated frequency of TICs in HAND2-AS1 overexpression and control HCC cells during serial transplantations.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Representative whole-body imaging of Huh7-Luc cells transduced with control or HAND2-AS1 overexpression vectors. Quantification for tumor numbers one month after tumor cells orthotopically implanted to B-NSG mice. (n = 5 mice per group).",
    "ncbi_link": "Luc: 
HAND2-AS1: 79804"
  },
  {
    "caption": "Biotin-RNA pulldowns were performed with nuclear extracts of oncosphere cells using full-length HAND2-AS1 transcript (sense), antisense, and one HAND2-AS1 intron control, followed by mass spectrometry. Band 1: INO80, band 2: RUVBL2.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "HAND2-AS1 was visualized by RNA FISH, followed by immunofluorescence staining of INO80 in HCC primary oncosphere cells. Scale bar, 100 μm.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Mapping analysis of INO80-binding domains of HAND2-AS1. Schematic diagram of HAND2-AS1 full-length and truncated fragments (top panel); Western blot of INO80 and RUVBL2 in RNA pulldown samples by different HAND2-AS1 fragments (middle panel); Different HAND2-AS1 fragments (bottom panel).",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "EMSA of biotin-labeled HAND2-AS1 (nt 83-242) probes incubated with INO80 protein.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Binding affinity of HAND2-AS1 with INO80 was determined by five independent EMSA assays. Non-linear regression curves were generated by GraphPad Prism. Results are shown as means ± SD.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Interaction regions of INO80 with HAND2-AS1 mutations at nt 83-242 of exon 2 were detected using RNA pulldown assays. LR, loop region.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "Representative whole-body imaging of Huh7-Luc cells transduced with control or INO80 shRNA #1 or shRNA #2 vectors. Quantification of tumor numbers of 4 weeks after tumor cells orthotopically implanted to B-NSG mice. Data are shown as means ± SD (n = 5 mice per group). One-way ANOVA with Dunnett's correction for multiple comparisons.",
    "ncbi_link": "Luc: 
INO80: 54617"
  },
  {
    "caption": "Macroscopic appearance of livers in 10.5-month-old DEN-treated Ino80flox/flox (Ino80+/+) and Ino80 knockout (Ino80-/-) (left panel). Black arrows indicate tumors. Quantitation of tumor foci numbers and areas in DEN-treated livers. Results are shown as means ± SD (n=10).",
    "ncbi_link": "Ino80: 68142"
  },
  {
    "caption": "Heatmap results for HAND2-AS1 or INO80 deficiency in HCC cells.",
    "ncbi_link": "HAND2-AS1: 79804
INO80: 54617"
  },
  {
    "caption": "Based on GSEA results, significantly changed genes due to depletion of HAND2-AS1 and INO80 were attributed to the BMP signaling in HCC primary cells. NES, normalized enrichment score; FWER, familywise error rate.",
    "ncbi_link": "HAND2-AS1: 79804
INO80: 54617"
  },
  {
    "caption": "ChIRP-seq analysis of HAND2-AS1 genomic binding at target sites in liver CSCs, using LacZ probes as negative control. A 10-kb interval centered on the called HAND2-AS1 peak is shown.",
    "ncbi_link": "LacZ: 
HAND2-AS1: 79804"
  },
  {
    "caption": "Representative ChIRP-seq of HAND2-AS1 binding of BMPR1A.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "Gel analysis of HAND2-AS1 RNA binding BMPR1A promoter in liver CSCs. LacZ and PVT1 served as negative controls.",
    "ncbi_link": "PVT1: 
LacZ: 
BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "HAND2-AS1 deletion in HCC cells decreases BMPR1A expression and inactivates BMP signaling.",
    "ncbi_link": "HAND2-AS1: 79804"
  },
  {
    "caption": "ChIRP-immunoblotting analysis of BMPR1A interaction with the INO80 complex in control and HAND2-AS1-knockout liver CSCs.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "EMSA analysis of the interaction of HAND2-AS1, INO80 and RUVBL2 with the BMPR1A promoter region.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "BMPR1A promoter binding region to HAND2-AS1/INO80 was deleted (BMPR1A-p-KO) in liver CSCs using lenti-Cas9, followed by HAND2-AS1 and INO80 overexpression (oeHAND2-AS1, oeINO80) for 36 h. BMPR1A mRNA levels were examined by realtime PCR. Data are shown as means ± SD. n=5. ** P < 0.01 by two-tailed Student's t test.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804
INO80: 54617
Cas9: 901176"
  },
  {
    "caption": "BMP signaling was examined in INO80-silenced liver CSCs by Western blot.",
    "ncbi_link": "INO80: 54617"
  },
  {
    "caption": "BMPR1A is highly expressed in HCC tumor tissues provided by Wang's cohort (GSE14520).",
    "ncbi_link": "BMPR1A: 657"
  },
  {
    "caption": "BMPR1A overexpression rescues sphere formation ability reduced by HAND2-AS1 depletion in HCC samples. Representative sphere formation is shown on the left panel. Scale bar, 100 μm. Percentages of sphere-forming cells were calculated as means ± SD (right panel). n=4.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "BMPR1A depletion reduces tumor-initiating capacity. n=12 mice per group.",
    "ncbi_link": "BMPR1A: 657"
  },
  {
    "caption": "Representative whole-body imaging of Huh7-Luc cells transduced with scramble (Ctrl) or BMPR1A shRNAs. Quantification for tumor numbers of 7 weeks after tumor cells orthotopically implanted to B-NSG mice. Calculated data are shown as means ± SD (n = 5 mice per group).",
    "ncbi_link": "Luc: 
BMPR1A: 657"
  },
  {
    "caption": "Representative H&E and immunohistological staining with Ki67 antibody in liver sections of 10-month-old DEN-treated WT and Bmpr1a-/- mice. Scale bar, 100 μm. Right: Quantitation of Ki67-positive cells in DEN-treated mice. Data are shown as means ± SD. n=5.",
    "ncbi_link": "Bmpr1a: 12166"
  },
  {
    "caption": "Representative whole-body imaging of Huh7-Luc cells in different groups. Mice treated with scramble ASOs and/or siRNAs obtained similar results to vehicle treatment. n≥5 mice in each group.",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Quantification of tumor numbers treated with ASOs and/or siRNAs after Huh7-Luc tumor cells orthotopically implanted to B-NSG mice. Calculated data are shown as means ± SD (n = 5).",
    "ncbi_link": "Luc: "
  },
  {
    "caption": "Representative H&E staining in liver sections from tumor-bearing mice treated with ASO1 and siBMPR1A in orthotopic transplants of tumors from HCC#50 and HCC#51. Scale bar, 100 μm.",
    "ncbi_link": "BMPR1A: 657"
  },
  {
    "caption": "Representative immunohistological staining with Ki67 antibody of tumor-bearing mice treated with ASO1 and siBMPR1A. Scale bar, 100 μm. Lower panel: Quantitation of Ki67-positive cells in different groups. Data are shown as means ± SD (n=5 per group).",
    "ncbi_link": "BMPR1A: 657"
  },
  {
    "caption": "Northern blotting of HAND2-AS1 and immunobloting of BMPR1A in tumors from PDX HCC#50 after treatment.",
    "ncbi_link": "BMPR1A: 657
HAND2-AS1: 79804"
  },
  {
    "caption": "Kaplan-Meier survival analysis of B-NSG mice orthotopically transplanted with PDXs HCC#50 (I) and HCC#51 (J). Treatment with ASO1 combined siBMPR1A causes synergistic therapeutic effect than each treatment alone (n = 10 per group). P value for Kaplan-Meier curves was determined using a Mantel-Cox log-rank test.",
    "ncbi_link": "BMPR1A: 657"
  },
  {
    "caption": "A-C Confocal images of Stage 12 embryos  from control, P{GT1}CG9005BG02278 P-element mutant (CG9005PBG), and CG9005PBG with CG9005 expression restored in macrophages. Macrophage: red. Phalloidin to visualize embryo: green. Germband edge: dotted white line. Data information: Scale bars: 50µm (A-C)",
    "ncbi_link": "CG9005: 36243"
  },
  {
    "caption": "D Quantification of macrophages that have penetrated the germband from genotypes in (A-C) and from  CG9005PBG over two deficiencies (Df) that remove the gene. n=35, 56, 25, 9, 18 embryos respectively, p<0.0001 for control vs CG9005PBG, Df1, or Df2; p=0.98 for control vs mac>CG9005 rescue, p=0.91, 0.90 for CG9005PBG vs Df1 or Df2. Data information: Throughout paper mac> indicates GAL4 driven expression of a UAS construct specifically in macrophages by  srpHemo-GAL4. N for movies represents imaging from different embryos. (D) One-way ANOVA with Tukey.",
    "ncbi_link": "CG9005: 36243
GAL4: 855828
srp: 41944"
  },
  {
    "caption": "E Macrophage-specific knockdown of CG9005 by UAS-RNAi lines. n=22, 20, 21, 23, 35, 28 embryos. p<0.0001 for all comparisons. Data information: Throughout paper mac> indicates GAL4 driven expression of a UAS construct specifically in macrophages by srpHemo-GAL4. N for movies represents imaging from different embryos. Unpaired t-tests. Graphs show mean±SEM; ns=p>0.05, *p<0.05, ****p<0.0001.",
    "ncbi_link": "CG9005: 36243
GAL4: 855828
srp: 41944"
  },
  {
    "caption": "F Stills from two-photon movies of control and CG9005PBG mutant embryos showing macrophages (nuclei, red) migrating starting at Stage 10 from the head towards the germband and invading the germband tissue. Elapsed time indicated in minutes. Germband edge (white dotted line) detected by yolk autofluorescence. Data information: Scale bars: 30µm (F). Throughout this work, embryos with stomadeal invagination and germband retraction away from the anterior of less than 29% were defined as Stage 10, 29%-31% Stage 11, and 35%-40% Stage 12.",
    "ncbi_link": "CG9005: 36243"
  },
  {
    "caption": "G-H Macrophage migration speed (G) in the head or (H) between the  yolk sac  and the germband edge. For (G): control n=8 movies, CG9005PBG mutant n=3; control n=360 tracks, mutant n=450, p=0.65. For (H): control n=7 movies, mutant n=3; control n=46 tracks, mutant n=19, p=0.62 Data information: Unpaired t-tests. Graphs show mean±SEM; ns=p>0.05, *p<0.05, ****p<0.0001.",
    "ncbi_link": "CG9005: 36243"
  },
  {
    "caption": "I The time required for the first macrophage nucleus to enter into the extended germband. Control n=7 movies, mutant n=5. Time to entry: control=23 min, CG9005PBG=38 min, p<0.0001. Data information: Unpaired t-tests. Graphs show mean±SEM; ns=p>0.05, *p<0.05, ****p<0.0001.",
    "ncbi_link": "CG9005: 36243"
  },
  {
    "caption": "C-D Confocal images or (D) quantification of the macrophages in germband in Stage 12 embryos from the control,  atosPBG, and  atosPBG expressing Atos itself or variants lacking particular domains. Transgene expression directly from macrophage specific promoter (mac-). For control (n=32 embryos) vs atosPBG mutant (n=56) p<0.0001; vs rescue with mac-atos (n=18) p>0.99; vs rescue with mac-atosDUF- (n=17) p=0.0003; vs rescue with mac-atosChrSeg-(n=21) p=0.0003; vs rescue with mac-atosDUF-/ChrSeg-(n=19) p=0,00014; vs rescue with mac-atosTAD1-/ TAD2- (n=25) p=0.0009, atosPBG mutant vs. rescue with mac-atos p=0.0031. Data information: Germband edge: dotted white line. Mac- indicates direct expression from the  srpHemo promoter. (C, macrophage nuclei (red), actin by Phalloidin staining (green). (D One-way ANOVA with Tukey. Mean±SEM, ns=p>0.05, **p<0.01, ***p<0.001, ****p<0.0001. Scale bars: 50µm (C",
    "ncbi_link": "atos: 36243
Atos: 36243
Hemo: 12798465
srp: 41944"
  },
  {
    "caption": "E Confocal images of atosPBG rescued by expressing Atossa's murine orthologs, mFAM214A or B (mFAMA-B) in macrophages, F Quantification of macrophages in the germband in Stage 12 embryos from the control, atosPBG, and atosPBG embryos expressing mFAM214A or B specifically in macrophages (mac-). For control (n=24 embryos) vs. atosPBG mutant (n=56) p<0.0001; vs mac-atos rescue (n=18) p=0.7; vs mac-mFAMA rescue (n=22) p=0.6; vs mac-mFAMB rescue (n=25) p=0.086. For atosPBG mutant vs mac-atos rescue p=0.0006; vs mac-mFAMA  rescue p=0.0002; vs mac-mFAMB rescue p=0.0043. Data information: Germband edge: dotted white line. Mac- indicates direct expression from the  srpHemo  promoter. E) macrophage nuclei (red), actin by Phalloidin staining (green). F) One-way ANOVA with Tukey. Mean±SEM, ns=p>0.05, **p<0.01, ***p<0.001, ****p<0.0001. Scale bars: 50µm E).",
    "ncbi_link": "atos: 36243
Atossa's: 36243
FAMA: 235493
FAM214A: 235493
FAMA-B: 230088
FAMB: 230088
srp: 41944"
  },
  {
    "caption": "B-D Confocal  images of early Stage 12  embryos from the control and lines expressing RNAis against (B)  porthos, (C) GR/HPR or (D) LKR/SDH, specifically in macrophages  (red). Germband edge: dotted white line. Data information: Scale bar: 50µm",
    "ncbi_link": "porthos: 35379
GR/HPR: 35347
LKR/SDH: 34064"
  },
  {
    "caption": "Quantification of the number of germband macrophages in embryos from control and upon RNAi knockdown of the genes In (E) control (n=36 embryos) vs. porthos RNAi (n=28) p<0.0001. In (F) сontrol 1 (n=18 embryos) vs. GR/HPR  RNAi 1 (n=18) and control 2 (n=21) vs. GR/HPR RNAi 2 (n=24), both p<0.0001; control 3 (n=15 embryos) vs. GR/HPR  RNAi 3 (n=23) p=0.08. Data information: Mean±SEM and ns=p>0.05, ****p<0.0001. One-way ANOVA with Tukey",
    "ncbi_link": "porthos: 35379
GR/HPR: 35347"
  },
  {
    "caption": "Quantification of the number of germband macrophages in embryos from control and upon RNAi knockdown of the genes In (G) сontrol 1 (n=18 embryos) vs. LKR/SDH RNAi 1 (n=17) and control 2 (n=21) vs. LKR/SDH  RNAi 2 (n=23), both p<0.0001. Data information: Mean±SEM and ns=p>0.05, ****p<0.0001. One-way ANOVA with Tukey",
    "ncbi_link": "LKR/SDH: 34064"
  },
  {
    "caption": "B Stills starting at Stage 11 from two-photon movies of control embryos and those expressing porthos (pths)-RNAi in  macrophages  (nuclei, red), migrating  from the  head mesoderm towards and into the germband at the indicated  time points. White dotted line: germband edge. Data information: Movies in each analysis set are from independent embryos. Scale bars: 30µm",
    "ncbi_link": "porthos: 35379
pths: 35379"
  },
  {
    "caption": "C-H Quantification of macrophage migration parameters from movies as in (B). Macrophage migration speed (C) in the head or (D) between the yolk sac and the germband  edge. (C) control n=4 movies, pths RNAi n=6; control n=507 tracks,  pths RNAi n=859; p=0.56. (D) control n=5 movies, pths RNAi n=5; control n=40 tracks, pths RNAi n=51; p=0.45. (E) The time required for the first macrophage nucleus to enter into the extended germband: control=23 min, CG9005PBG=38 min, p<0.0001. The migration speed of the (F) 1st, (G) 2nd, or (H) 3rd-5th macrophages  along the first 25-30µm into the germband between the mesoderm and ectoderm: control=21.5 min, n=6, pths RNAi=36.2 min, n=4, p<0.0001. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Unpaired t-test",
    "ncbi_link": "CG9005: 36243
pths: 35379"
  },
  {
    "caption": "I Confocal images of early Stage 12 embryos  from control, atosPBG, and atosPBG expressing atos::FLAG::HA (mac>atos) or  pths::FLAG::HA (mac>pths) in macrophages (red). Embryo detected by phalloidin staining (green). White dotted line: germband  edge.. J Quantification of macrophages  in the  germband  of an atosPBG mutant rescued by expressing pths::FLAG::HA in macrophages. For control (n=15 embryos) vs atosPBG mutant (n=22) and  mac>atos  rescue (n=27) both p<0.0001, vs mac>pths rescue (n=30) p=0.0007. Data information: Movies in each analysis set are from independent embryos. Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. one-way ANOVA with Tukey Scale bars: 50µm",
    "ncbi_link": "FLAG: 
HA: 
atos: 36243
pths: 35379"
  },
  {
    "caption": "E-F Confocal images of early Stage 12 embryos from the controls, from lines expressing  nlacZ  and RNAis against  atos or  pths in macrophages (mac>) as a second control, and lines expressing RNAis targeting atos  or pths along with individual components of the dTORC1  pathway in macrophages, including Nrpl2, Iml1, and TSC1. Germband edge: dotted white line. Data information: Scale bar: 30µm",
    "ncbi_link": "lacZ: 
atos: 36243
pths: 35379
Iml1: 38176
Nrpl2: 32677
TSC1: 42862"
  },
  {
    "caption": "G-H Quantification of the number of germband macrophages in embryos from the controls and upon RNAi knockdown of the genes in E-F. Expression of different RNAis against Nrpl2, Iml1, and TSC1 in atos or pths-depleted macrophages rescues macrophage invasion into the germband while expression of lacZ does not. In (G) control (n=21 embryos) vs. atos RNAi (n=30) p<0.0001; control vs. atos RNAi rescued with Nrpl2 RNAi (n=32) p=0.019, with Iml1 RNAi (n=24) p=0.03, and with TSC1 RNAi (n=15) p=0.04. In (H) control (n=29 embryos) vs pths RNAi (n=26) p<0.0001; control vs. pths RNAi rescued with Nrpl2 RNAi (n=27) p=0.01, with Iml1 RNAi (n=17) p=0.02, and with TSC1 RNAi (n=18) p=0.02. Data information: Mean±SEM, ns=p>0.05, *p<0.05, ****p<0.0001. one-way ANOVA with Tukey",
    "ncbi_link": "lacZ: 
atos: 36243
pths: 35379
Iml1: 38176
Nrpl2: 32677
TSC1: 42862"
  },
  {
    "caption": "I  Western blot  of protein extracts from control and pths  KD S2R+ probed with p-4EBP1 antibody.  Tubulin serves as a loading control and quantification normalized to loading control. N=3 biological replicates for both control and  pths KD, p=0.69. Data information: Mean±SEM, ns=p>0.05, *p<0.05, ****p<0.0001. unpaired t-test",
    "ncbi_link": "pths: 35379"
  },
  {
    "caption": "C-F RT-qPCR analysis of mRNA from ribosomal  protein fractions for control (black) and pths KD (gray) transcripts from S2R+ cells. RNA was isolated individually from fractions and pooled into five categories: RNP, 40S/60S, monosome, low polysome (di- and trisome), and high polysome (remaining fractions). The data were plotted relative to the amount present in the monosome fraction for each transcript. The mRNA levels of subunits of mitochondrial complexes (C) I, (D) III and (E) V were reduced in low and high polysome fractions in pths KD cells compared to the control cells, while (F) mRNA levels of GAPDH in the same fractions, used as an internal control, were not changed (n=3 independent biological replicates for control and pths KD). For (C,E-F) low polysome fraction for control vs. pths KD: (C) p=0.057, (D) p=0.0039, (E) p=0.09, (F) p=0.5. For (C,E-F) high polysome fraction for control vs. pths KD: (C) p=0.039, (D) p=0.046, (E) p=0.041, (F) p=0.66. G-I Western blots and their quantifications of protein extracts from control and pths KD S2R+ probed with (G)  MT-ND1 (for mitochondrial complex I) n=4, p<0.0001), (H) ATPsynt-β (for mitochondrial complex V) n=3 p=0.034 and (I)  tubulin β antibodies p=0.56) (n=3). Profilin serves as loading control. N=biological replicates. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. Unpaired t-tests (C-F, G-I).",
    "ncbi_link": "GAPDH: 
pths: 35379"
  },
  {
    "caption": "B The Oxygen Consumption Rate (OCR, pmols  O2/min) assessed as a representative parameter of OxPhos in control and pths-KD S2R+ cells by a Seahorse efflux assay. n≥3 independent biological experiments each with n>6 technical replicate. Data information: Mean±SEM, **p<0.01, ***p<0.001, ****p<0.0001. Unpaired t-tests",
    "ncbi_link": "pths: 35379"
  },
  {
    "caption": "Confocal images of germband macrophages in control embryos and those expressing different RNAis against mitochondrial OxPhos Complex III (or an RNAi against Complex V. Data information: show Stage 12 embryos.  Complex III RNAis target Cyt-c1, UQCR-cp1-2, for Complex V, ATP synthase F1F0. Scale bars: 50µm",
    "ncbi_link": "Cyt-c1: 38612
UQCR-cp1: 41800"
  },
  {
    "caption": "quantification of germband macrophages in control embryos and those expressing different RNAis against mitochondrial OxPhos Complex III (or an RNAi against Complex V. For (H) control (n=34 embryos) vs Complex III RNAi 1 (n=20) p=0.0001; vs. Complex III RNAi 2 (n=18) p=0.027; vs. Complex III  RNAi 3 (n=16) p<0.0001; vs. Complex V RNAi (n=14) p<0.0001. Data information: show Stage 12 embryos. Complex III  RNAis target Cyt-c1, UQCR-cp1-2, for  Complex V,  ATP synthase F1F0. Mean±SEM, **p<0.01, ***p<0.001, ****p<0.0001. one-way ANOVA with Tukey's (H).",
    "ncbi_link": "Cyt-c1: 38612
UQCR-cp1: 41800"
  },
  {
    "caption": "I Single plane  confocal microscope  image during germband entry from control or atosPBG embryos, or those expressing  pths-RNAi or CV-DN in macrophages. Antibodies against S293-phosphorylated inactivated  Pyruvate Dehydrogenase (pPDH, green) or total PDH (magenta) in  macrophages (red). Higher pPDH levels are usually found when  ATP/ADP  levels are high and input into the TCA cycle is being downregulated Data information: show Stage 12 embryos. Scale bars: 10µm",
    "ncbi_link": "atos: 36243
pths: 35379"
  },
  {
    "caption": "J Quantification of normalized pPDH/PDH levels calculated from fluorescence intensities in macrophages from the genotypes in (I) during initial germband  invasion. The pPDH/PDH ratio is significantly reduced, arguing that decreased function of CV, Atos  or Pths in macrophages results in lower cellular ATP/ADP ratios compared to the control. N=3 independent experiments. Ctrl 1 (n=10 embryos) vs CV-DN  (n=9) and vs.  atos  mutant (n=13) both p=0.0002; Ctrl 2 (n=7 embryos) vs pths RNAi (n=8) p=0.0001.*** shown above columns in J are for comparison to relevant control. Data information: Mean±SEM, **p<0.01, ***p<0.001, ****p<0.0001. Unpaired t-tests",
    "ncbi_link": "atos: 36243
Atos: 36243
Pths: 35379
pths: 35379"
  },
  {
    "caption": "A Single plane confocal microscope  image during germband entry from control or atosPBG embryos, or those expressing pths, GR/HPR, and LKR/SDH in macrophages (mac>). Embryos were stained  for antibodies against S293-phosphorylated inactivated Pyruvate Dehydrogenase (pPDH, green) or total PDH (magenta) in macrophages (red). Higher pPDH/PDH ratios are consistent with higher  ATP/ADP  levels. Data information: Scale bars: 10µm",
    "ncbi_link": "atos: 36243
pths: 35379
GR/HPR: 35347
LKR/SDH: 34064"
  },
  {
    "caption": "B Quantification of normalized pPDH/PDH levels calculated from fluorescence intensities in macrophages from the genotypes in (A) during initial germband invasion. The pPDH/PDH ratio is significantly increased in  atosPBG embryos expressing either  pths, GR/HPR, or LKR/SDH in macrophages compared to the atosPBG embryos. This argues that the decreased Atos  function in atosPBG macrophages, resulting in lower cellular ATP/ADP ratios, was restored by expressing either its targets or murine orthologs. N=3 independent experiments. Control (n=9 embryos) vs.  atos mutant (n=10) p<0.0001. Control vs. atos mutant rescued with mac>pths (n=10) p=0.77; rescued with  mac>GRHPR (n=9) p=0.48; rescued with mac>LKRSDH (n=10) p=0.012. For  atos mutant vs. atos rescued with  mac>pths or  mac>GRHPR p<0.0001. vs. atos rescued with  mac>LKRSDH p=0.0014. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. One-way ANOVA with Tukey",
    "ncbi_link": "atos: 36243
Atos: 36243
pths: 35379
GR/HPR: 35347
GRHPR: 35347
LKR/SDH: 34064
LKRSDH: 34064"
  },
  {
    "caption": "C-D (C) Confocal images or (D) quantification of the  macrophages in germband  in Stage 12 embryos from the control, atosPBG, and atosPBG expressing atos itself or  GR/HPR, or LKR/SDH in macrophages. Germband edge: dotted white line. For (D) control (n=29 embryos) vs. atos mutant (n=19) p<0.0001. Control vs. atos  mutant rescued with  mac>atos (n=27 embryos) p=0.99; rescued with  mac>GRHPR (n=28) p=0.29; rescued with mac>LKRSDH (n=20) p=0.036. atos  mutant vs. atos  rescued with   mac>atos or mac>GRHPR p<0.0001; rescued with mac>LKRSDH p=0.0134. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. One-way ANOVA with Tukey Scale bars: 50µm",
    "ncbi_link": "atos: 36243
GR/HPR: 35347
GRHPR: 35347
LKR/SDH: 34064
LKRSDH: 34064"
  },
  {
    "caption": "E Single plane confocal microscope images during germband entry from control or atosPBG embryos, or those expressing mammalian orthologs mFAM214A or B (FAMA-B) in  macrophages  (mac>). Embryos were stained for antibodies against S293-phosphorylated inactivated Pyruvate Dehydrogenase (pPDH, green) or total PDH (magenta) in macrophages  (red). Data information: Scale bars: 10µm",
    "ncbi_link": "atos: 36243
FAM214A: 235493
FAMA-B: 230088"
  },
  {
    "caption": "F Quantification of normalized pPDH/PDH levels measured from fluorescence intensities in  macrophages from the genotypes in (E) during initial germband invasion. The pPDH/PDH ratio is significantly increased in  atosPBG embryos  expressing either mammalian ortholog mFAM214A or B in macrophages compared to the  atosPBG embryos. Results from three independent experiments. Control (n=10 embryos) vs. atos mutant (n=11) p<0.0001. Control vs. atos  mutant rescued with mac-mFAMA (n=14 embryos) p=0.06; rescued with mac-mFAMB (n=12) p=0.13. atos mutant vs. atos mutant rescued with mac-mFAMA p=0.0025 or  mac-mFAMB p=0.0019. Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. One-way ANOVA with Tukey",
    "ncbi_link": "atos: 36243
FAM214A: 235493
FAMA: 235493
FAMB: 230088"
  },
  {
    "caption": "Cellular metabolites were measured by  LC-MS-based untargeted metabolomics from extracts of Stage 11 embryos; biological replicates for control n=5, for atosPBG n=7. (B) Normalized ATP/ADP ratio values are decreased in atosPBG compared to control embryos  (p=0.028). Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. unpaired t-test",
    "ncbi_link": "atos: 36243"
  },
  {
    "caption": "Cellular metabolites were measured by LC-MS-based untargeted metabolomics from extracts of Stage 11 embryos; biological replicates for control n=5, for atosPBG n=7. Heatmap of non-targeted metabolites in atosPBG compared to wild-type embryos shown with average log2fold change (FC) in the non-targeted  LC-MS/MS analysis reveals (C) an increase in atosPBG in substrates of the dGR/HPR  enzyme, including 4-hydroxy α-ketoglutarate and hydroxyproline (HLP) and a smaller decrease in its products, glycolate and glycerate, (D) a significant increase in some dipeptides including those containing  hydroxyproline. Data information: Values in heat maps are obtained from untargeted  metabolomic analysis, unpaired t-test",
    "ncbi_link": "atos: 36243"
  },
  {
    "caption": "Cellular metabolites were measured by LC-MS-based untargeted metabolomics  from extracts of Stage 11 embryos; biological replicates for control n=5, for  atosPBG n=7. (E) Quantification shows an increase in atosPBG in the pyruvate/glucose ratio (p=0.035), but none for the  lactate/glucose ratio (p=0.65). Data information: Mean±SEM, ns=p>0.05, *p<0.05, **p<0.01, ****p<0.0001. unpaired t-test",
    "ncbi_link": "atos: 36243"
  },
  {
    "caption": "Cellular metabolites were measured by LC-MS-based untargeted metabolomics  from extracts of Stage 11 embryos; biological replicates for control n=5, for  atosPBG n=7. Heatmap of non-targeted metabolites in atosPBG compared to wild-type embryos  shown with average log2fold change (FC) in the non-targeted  LC-MS/MS analysis (F) We observe increases in atosPBG in intermediates of mitochondrial fatty acid β-oxidation (FAO), including different carnitine-conjugated lipids, and (F-G) a significant increase in ketone body substituents compared to the control. Data information: Values in heat maps are obtained from untargeted metabolomic analysis, unpaired t-test",
    "ncbi_link": "atos: 36243"
  },
  {
    "caption": "WM983 and UACC257 human melanoma cells were transfected with Perfringolysin O (PFO)-mCherry D4H cholesterol sensor and plated on glass coverslips. Cells were exposed to UV (0 or 175 J/m2) and incubated for 0, 2 or 5 weeks as indicated. (H) Representative cell images. (I) Fluorescence intensity from cells analyzed in (H) was measured and quantified using LASX analysis software (N≥8 biological replicates); data displayed are mean±SEM. Data was analyzed using 1-way ANOVA with multiple comparisons (WM983, p < 0.001; UACC257 p > 0.05). **p<0.01, ***p<0.001, ****p<0.0001.",
    "ncbi_link": "mCherry: 
Perfringolysin O: 69447922
PFO: 69447922"
  },
  {
    "caption": "O1C78 WM983 cells expressing the PFO-mCherry D4H cholesterol sensor were examined as in panels H and I (N≥8 biological replicates); data displayed are mean±SEM.",
    "ncbi_link": "mCherry: 
PFO: 69447922"
  },
  {
    "caption": "(D) SOCE in primary patient samples exhibiting NRAS (8 of 27 samples), BRAF (6 of 27 samples), TERT promoter (6 of 27 samples), NF1 (5 of 27 samples), and CDKN2A (5 of 27 samples) alterations were compared to SOCE in samples that expressed WT or the unaltered gene. Data displayed as mean±SEM.",
    "ncbi_link": "BRAF: 673
CDKN2A: 1029
NF1: 4763
NRAS: 4893
TERT: 7015"
  },
  {
    "caption": "Expression of ERα in control (shCtrl) and knockdown (shERα) BM67 cells was determined by western blotting (β-actin served as a loading control). Gene expression was determined using polysome-profiling which quantifies both total mRNA and efficiently translated polysome-associated mRNA (n = 3).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Distributions (quantified by kernel density estimation) of p-values for differential expression (shERα vs. shCtrl BM67 cells) using data from polysome-associated mRNA (orange), cytosolic mRNA (purple) or from analysis of changes in translational efficiency (i.e. changes in polysome-associated mRNA not paralleled by changes in cytosolic mRNA) leading to altered protein levels (red; a higher density of low p-values indicates a higher frequency of changes in gene expression).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Scatterplot of polysome-associated mRNA vs. cytosolic mRNA log2 fold-changes (shERα vs. shCtrl). Areas of the plot are colored according to the density of data points (genes; dark blue corresponds to areas with many genes",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Targets from each mode of regulation (cf. Fig 1E) were selected for validation by Nanostring. Shown is a scatterplot of Nanostring quantification of polysome-associated mRNA vs. cytosolic mRNA log2 fold-change (shERα vs. shCtrl; n = 3). Genes are colored according to their identified mode of regulation (i.e. from Fig 1E). Confidence ellipses (based on Nanostring data, level 0.7) are overlaid for each mode of regulation. Selected genes from each mode of regulation are indicated.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Levels of indicated proteins from shERα and control BM67 cells were determined by western blotting with their quantifications. β-actin served as loading control. Graphs represent mean ± standard deviation (n = 3-5 as indicated). Protein expression between groups were compared using two-sided paired Student's t tests.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "nanoCAGE sequencing was applied to determine transcription start sites in shERα BM67 cells. The number of detected transcription start sites (peaks) and RefSeq transcripts when sampling increasing number of RNAseq reads are indicated to evaluate the complexity of nanoCAGE RNAseq libraries.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Volcano plot of ERα dependent miRNA expression in BM67 cells quantified by small RNAseq. Down- and up-regulated miRNAs (FDR<0.2 and fold-change > 1.25) are colored in blue and red, respectively.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Validation of miRNA expression using qPCR. Normalized expression (mean ± standard deviation; n = 3) (B) and expression fold change (shERα vs. shCtrl) obtained from small RNAseq vs. qPCR (C).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Percentage of miRNA among small RNAs in shERα and shCtrl BM67 cells (mean ± standard deviation; n = 3).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Assessment of the relationship between presence of miRNA target sites and translational offsetting. (E) For visualization, mRNAs were assigned angles describing their mode of regulation such that mRNAs with congruently modulated total and polysome-associated mRNA obtain an angle of ~45 degrees, whereas offset mRNAs are assigned an angle of ~0 degrees. (F) The distributions (quantified by kernel density estimation) of such angles were then compared between mRNAs whose levels were induced upon ERα depletion, which were also targets of each suppressed miRNAs separately (blue lines); and the set of background transcripts (mRNAs induced upon ERα depletion but not targets of suppressed miRNAs; black). (G) For such subsets of miRNA targets (i.e. from F), the relative number of offset and non-offset mRNAs (as determined by anota2seq analysis) was also compared to the background (same as in F) using Fisher's exact test; and the resulting adjusted p-values (FDRs; across all assessed miRNAs) were visualized as a histogram. (H-I) A similar assessment as in (F-G) but for suppressed mRNAs and induced miRNAs. (J) A similar assessment as in (H) but for randomly selected groups of 10 miRNAs (gray lines) compared to background (black) and targets of all induced miRNA (red; i.e. from H).",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "For each codon, the average frequency (per thousand) is compared between transcripts induced but offset vs non-offset (i.e. abundance mode of regulation) upon ERα depletion in BM67 cells. Codons for the same amino acid are connected by a gray line. Heatmap of standardized residuals from a chi-squared contingency table test. Shown in red and blue are cells with counts significantly higher and lower, respectively, than expected counts under the null hypothesis (i.e. independence between mode for regulation of gene expression and codon composition). A correspondence analysis for average codon frequency among transcripts annotated to each GO term. Each gray dot corresponds to one GO term. The gene expression modes observed upon ERα depletion (Fig 1E) were then projected into the same dimensions based on the average codon frequencies of included transcripts. A correspondence analysis for codon frequency in each regulated mRNA (from Fig 1E). Each dot represents one mRNA and is colored according to its mode of regulation. Codons identified as over-represented among translationally offset mRNAs are also indicated. Unsupervised clustering of gene level codon usage normalized by amino acid counts. All regulated mRNAs (from Fig 1E) are shown in rows and all codons in columns. Codons identified as over-represented among mRNAs whose levels were induced but offset or suppressed but offset are indicated in light and dark blue, respectively.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "Immunoblotting of BM67 cell extract for ELP3 after stable shRNA-mediated ERα knockdown in BM67 cells. Graphs represent mean ± standard deviation of n=3.",
    "ncbi_link": "ERα: 13982"
  },
  {
    "caption": "qPCR analysis and immunoblotting of BM67 cell extract for indicated proteins with its quantitation following deletion of Esr1 gene by CRISPR-Cas9 technology. Graphs represent mean ± standard deviation of n=5.",
    "ncbi_link": "Esr1: 13982"
  },
  {
    "caption": "qPCR analysis and immunoblotting of BM67 cell extract for ELP3 and DEK with its quantitation following deletion of Elp3 gene by CRISPR-Cas9 technology. Graphs represent mean ± standard deviation of n=4.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Immunoblotting and qPCR analysis comparing cell extracts obtained from BM67 cells transduced with pLentiCRISPRV2 empty vector, Elp3-null BM67 cells and Elp3-null BM67 cells overexpressing ELP3 protein containing silent mutations in the sgRNA binding site. Graphs represent mean ± standard deviation of n=3-4.",
    "ncbi_link": "Elp3: 74195"
  },
  {
    "caption": "Boxplots (plotted as in Fig 3B) of gene expression of ELP3, ALKBH8 and CTU2 upon treatment with 17β-E2 and/or ICI-182780 in MCF7 cells (extracted from (Wardell et al, 2012; Data Ref: McDonnell et al, 2012)). Wilcoxon-Mann-Whitney tests (two-sided) were used to assess differences between conditions (n = 10) and a global Bonferroni adjustment was applied on p-values.",
    "ncbi_link": "ALKBH8: 91801
CTU2: 348180
ELP3: 55140"
  },
  {
    "caption": "ChIP-seq reveals ER binding sites proximal to the ELP3 gene. Each track represents a distinct ChIP-seq dataset.",
    "ncbi_link": "ELP3: 55140"
  },
  {
    "caption": "Immunoblotting of MCF-7 cell extract for indicated proteins following deletion of ELP3 gene by CRISPR-Cas9 technology.",
    "ncbi_link": "ELP3: 55140"
  },
  {
    "caption": "Quantification of mcm5S2-U, mcm5U and cm5U levels in ELP3-null MCF-7 cells and in MCF-7 cells treated with 100 nM ICI-182780 for 72 hours versus their respective controls by liquid chromatography-mass spectrometry (LC-MS) analysis. The MCF-7 cells were grown in phenol red-free RPMI media supplemented with 5% charcoal-stripped serum for 24 hours prior to ICI-182780 treatment. Graphs represent mean ± SD of n=4. Data were analyzed using two-sided paired Student's t tests. Vh, Vehicle; ICI, ICI-182780.",
    "ncbi_link": "ELP3: 55140"
  },
  {
    "caption": "C Quantitative analysis of lysosomal movement from kymographs. Results were expressed as percent of total lysosomes (N = 44, 49, and 16 neurons for shSc, shLAMTOR1, and shLAMTOR+rLAMTOR1 respectively from 3-10 independent experiments). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by two-way ANOVA with Tukey's *P < 0.05, **P < 0.01, ***P < 0.001, as compared to shSc; #P < 0.05, ###P < 0.001, as compared to shLAMTOR1 n.s., not significant.",
    "ncbi_link": "LAMTOR: 66508
LAMTOR1: 66508"
  },
  {
    "caption": "G FRAP  analysis of dendritic lysosome movement. Quantitative analysis for F (N = 7, 7, and 9  neurons for shSc, shLAMTOR1, and shLAMTOR+rLAMTOR1, respectively, from 3 independent experiments). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by Dunnett's post-test *P < 0.05, **P < 0.01, ***P < 0.001, as compared to shSc; #P < 0.05, ###P < 0.001, as compared to shLAMTOR1 ; n.s., not significant.",
    "ncbi_link": "LAMTOR: 66508
LAMTOR1: 66508"
  },
  {
    "caption": "A Representative kymographs of  LysoTracker-labeled  lysosomes in  proximal dendrites  of  hippocampal neurons  infected with scrambled shRNA (shSc), LAMTOR2  shRNA (shLAMTOR2), or Raptor shRNA (shRaptor). Scale bar, 5 µm. B Quantitative analysis of lysosomal movement  from kymographs (N = 44, 24, and 19 neurons for shSc, shLAMTOR2, and shRaptor, respectively, from 3-10 independent experiments). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by two-way ANOVA with Sidak's post-test ***P < 0.001 as compared to shSc; n.s., not significant.",
    "ncbi_link": "LAMTOR2: 83409
Raptor: 74370"
  },
  {
    "caption": "C, D FRAP  analysis of dendritic lysosomal movement in Raptor  KD neurons. C Representative images of a  neuron at 0 and 4 min after photobleaching. D Quantification of the  lysosomes in C undergoing retrograde (red) or  anterograde (cyan) transport (N = 7 and 8 neurons for shSc and shRaptor, respectively, from 3 independent experiments). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by Mann-Whitney U test ***P < 0.001 as compared to shSc; n.s., not significant.",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "E LAMTOR1 KD did not affect trafficking of vesicles labeled with Alexa 594-conjugated transferrin (red, Tf  594) in dendrites. Shown are dendritic segments (upper) and kymographs (lower). Scale bar, 5 µm. F Quantitative analysis of  vesicular movement from  kymographs (N = 10 neurons from 3 independent experiments). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by Mann-Whitney U test ***P < 0.001 as compared to shSc; n.s., not significant.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "A Quantification of the percent of lysosomes moving in the anterograde or retrograde direction in neurons infected with AAV  expressing either LAMTOR1 shRNA (shLAMTOR1) or scrambled shRNA (shSc) and Accell lyspersin siRNA or control siRNA. Neurons were imaged with LysoTracker  to visualize lysosomal  trafficking in dendrites. N = 17-31  neurons  from 3-6 independent experiments. Data information: Data with error bars are represented as means ± SEM. ***P < 0.001 compared with shSc or shSc/Accell siControl; ##P < 0.01, ###P < 0.001 compared with shLAMTOR1 or shLAMTOR1/Accell siControl; &&P < 0.01, &&&P < 0.001 compared with shSc/Accell siLyspersin; n.s., not significant; two-way ANOVA with Tukey's post-test.",
    "ncbi_link": "lyspersin: 71923
Lyspersin: 71923
LAMTOR1: 66508"
  },
  {
    "caption": "C-F Quantification of the percent of lysosomes moving in the anterograde  or  retrograde direction. C, E, F Cultured  hippocampal neurons  were infected with AAV  expressing either shLAMTOR1 or shSc; they were treated with vehicle control or ML-SI1 (20 µM, C, n = 16-49 neurons from 3-10 independent experiments), or  ML-SA1 (20 µM, E, n = 13-49  neurons from 3-10 independent experiments), or  CilioD (20 µM, F, n = 12-49  neurons from 3-10 independent experiments), and imaged with  LysoTracker to visualize lysosomal  trafficking in dendrites. D Neurons  were infected with shLAMTOR1 or shSc AAV and Accell TRPML1 siRNA or control siRNA; they were imaged as described above. N = 7-31 neurons from 3-6 independent experiments. Data information: Data with error bars are represented as means ± SEM. ***P < 0.001 compared with shSc or shSc/Accell siControl; ##P < 0.01, ###P < 0.001 compared with shLAMTOR1 or shLAMTOR1/Accell siControl; &&P < 0.01, &&&P < 0.001 compared with shSc/Accell siLyspersin; n.s., not significant; two-way ANOVA with Tukey's post-test.",
    "ncbi_link": "Lyspersin: 71923
LAMTOR1: 66508
TRPML1: 94178"
  },
  {
    "caption": "D  TAT-2031 treatment (10 µM) increased ML-SA1-induced   TRPML1 Ca2+  release in both control and  LAMTOR1 KD cells. Data information: traces represent the mean values of each group.",
    "ncbi_link": "LAMTOR1: 55004"
  },
  {
    "caption": "I Both LAMTOR1 KD and TAT-2031  treatment (10 µM) increased ML-SA1-induced TRPML1-GCaMP6m responses in neurons. J Quantification of peak responses as shown in I. N = 6-13 cells from 3 independent experiments. Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by two-way ANOVA with Tukey's post hoc analysis *P < 0.05, **P < 0.01, ***P < 0.001, ###P < 0.001, n.s., not significant. traces represent the mean values of each group.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "K LAMTOR1 KD increased PI(3,5)P2 (0.5 µM)-induced  TRPML1-GCaMP6m responses and the blocking effect of ML-SI1  treatment (20 µM). L Quantification of peak  TRPML1-GCaMP6m responses as shown in K. N = 6-16 cells from 3 independent experiments. Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by two-way ANOVA with Tukey's post hoc analysis *P < 0.05, **P < 0.01, ***P < 0.001, ###P < 0.001, n.s., not significant. traces represent the mean values of each group.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "A-D Effects of  LAMTOR1 KD and ML-SI1 treatment on TBS-induced LTP (A) or  LFS-induced  LTD (C) in CA1. B, D Means ± SEM of fEPSPs measured 40 min after TBS (B, n = 4-5 slices from 4-5 mice) or LFS (D, n = 4-8 slices from 4-8 mice) in different groups. Data information: Slopes of fEPSPs  were normalized to the average values recorded during the first 10 min baseline Statistical significance was assessed by two-way ANOVA with Tukey's post-test *P < 0.05, **P < 0.01, ***P < 0.001 compared with shSc P < 0.05, ##P < 0.01, ###P < 0.001 compared with shLAMTOR1. Insets show representative traces of evoked fEPSPs before and 40 min after TBS/LFS. Scale bar 0.5 mV/10 ms.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "K Effects of LAMTOR1 KD and treatment with a calcineurin  inhibitor, FK506, on LFS-induced  LTD in  CA1. L Means ± SEM of fEPSPs measured 45 min after LFS in different groups (n = 3-4 slices from 3-4 mice). Data information: Slopes of fEPSPs were normalized to the average values recorded during the first 10 min baseline Statistical significance was assessed by two-way ANOVA with Tukey's post-test *P < 0.05, **P < 0.01, ***P < 0.001 compared with shSc, Vehicle, or TAT, #P < 0.05, ##P < 0.01, ###P < 0.001 compared with shLAMTOR1. Insets show representative traces of evoked fEPSPs before and 40 min after  LFS. Scale bar 0.5 mV/10 ms.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "LAMTOR1  KD significantly reduced levels of GluA1 phosphorylation and total GluA1 as well as the ratio of p-GluA1 to GluA1 in hippocampal neurons, and this effect was reversed by ML-SI1 treatment. A Representative images of CA1 pyramidal neurons stained with anti-p-GluA1  S845 (magenta), anti-GluA1 (red), and anti-GFP (green) antibodies. Scale bar = 20 µm.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "A  Mice received 10 min of training in an environment with two identical objects and received a retention test 24 h later in which one object was replaced with a novel one. LAMTOR1 shRNA-injected mice  exhibited a significant deficit 24 h after training, which was reversed by ML-SI1 treatment (N = 7-18 mice). B % freezing for different experimental groups in context memory (N = 7-19 mice). Data information: Data with error bars are represented as means ± SEM. Statistical significance was assessed by two-way ANOVA with Tukey's post-test. *P < 0.05, ***P < 0.001, as compared to shSc; #P < 0.05, ###P < 0.001, as compared to shLAMTOR1.",
    "ncbi_link": "LAMTOR1: 66508"
  },
  {
    "caption": "Paneth cell quantification on Lgr5-DTReGFP duodenum (Duo) and Ileum (Ile). Left panel: Representative images of Lendrum's staining that evidence Paneth cell granules. Arrows show differentiated Paneth cells. Right panel: quantification of the Paneth cells per 10 intervilli regions. Each symbol indicates the value for a given embryo.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Expression analysis by qRT-PCR of the indicated Paneth cell markers in Lgr5-DTReGFP ileums (n= 8 WT, 12 HE, 10 KO).",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "X-gal staining in Axin2Lac/+-Lgr5-GFP-CreERT2 WT or KO ileums.",
    "ncbi_link": "GFP: 
Lac: 
Axin2: 12006
Cre: 2777477
ERT2: 2099
Lgr5: 14160"
  },
  {
    "caption": "Gene expression analysis by qRT-PCR of stem cell markers in Lgr5-DTReGFP ileums (n= 3 WT, 6 HE, 6 KO).",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "FACS quantification of the number of eGFP+ve (ISC) cells per small intestine at the indicated developmental stages in Lgr5 HEs and Lgr5 KOs. Each symbol indicates the value for a given embryo. Mean value for each group is depicted on the graph.",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "Influence of mouse Rspondin 1 concentration on growth of replated Lgr5-DTReGFP WT and Lgr5 KO organoids after 5 days of culture.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Paneth cell quantification on Lgr5-DTReGFP ileums. Each symbol indicates the value for a given embryo.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Immunofluorescence showing Olfm4+ve cells in Lgr5-DTReGFP duodenums. Cell membranes are shown with b-catenin and nuclei were counterstained with DAPI. Quantification of Olfm4+ve cells per intervilli regions in duodenum and ileum. Each symbol indicates the value for a given embryo.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Axin2 expression levels detected by RNAscope on Lgr5-DTReGFP proximal intestine.",
    "ncbi_link": "eGFP: 
Axin2: 12006
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Gene expression analysis by qRT-PCR of stem cell and differentiation markers in Lgr5-DTReGFP ileums (vehicle-treated: 7 WT and 7 KO; LGK974-treated: 3 WT and 7 KO).",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Representative pictures of lineage tracing in Lgr5-expressing or Lgr5 cKO intestine after 10 days of chase and quantification of the number of traced clones per recombined surface at PN18 (ileum). Each symbol indicates the value for a given mouse.",
    "ncbi_link": "Lgr5: 14160"
  },
  {
    "caption": "Representative immunofluorescence pictures showing Paneth cells (Plyz+ve) in traced clones (RFP+ve) from control (Lgr5Cre/+) and cKO (Lgr5Cre/flox) PN18 and adult ileums. Arrow heads point to Plyz+ve cells in traced clones. Quantification of the number of Paneth cell number per recombined RFP+ve crypt on control and cKO ileums in PN18. Each symbol indicates the value for a given mouse.",
    "ncbi_link": "Cre: 2777477
Lgr5: 14160"
  },
  {
    "caption": "ISC (eGFP+ve) cells were FACS-sorted from Lgr5-DTReGFP embryos at E16.5 and subjected to RNAseq analysis. Heatmap of differentially regulated genes in HE and KO ISCs at E16.5. Biological replicates for RNAseq experiments on ISC Lgr5-DTReGFP E16.5 independent embryonic pools, each obtained from independent litters (n= 2 HE, 2 KO)",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Compared Hallmarks for upregulated and downregulated genes in the transcriptome of E16.5 Lgr5 KOs vs E16.5 HEs, adult HEs vs E18.5 HE embryos and adult Lgr5-Cre cKO vs HEs. * Asterisks refer to given pathways for which differentially modulated genes were found upregulated and downregulated. Right panels: GSEA showing enrichment of the epithelial to mesenchymal transition (EMT) data set in E16.5 Lgr5 KOs vs E16.5 HEs, adult HEs vs E18.5 HE embryos, and adult Lgr5 cKO vs adult HE modulated genes. NES: Normalized Enrichment Score. Biological replicates for RNAseq experiments on ISC Lgr5-DTReGFP E16.5 independent embryonic pools, each obtained from independent litters (n= 2 HE, 2 KO); Lgr5-DTReGFP E18.5 individual embryos (n=2 HE) and Lgr5-DTReGFP adult individual animals (n=2 HE); Lgr5-Cre/flox adult individual animals (n= 2 HE, 3 cKO).",
    "ncbi_link": "eGFP: 
Cre: 2777477
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Expression levels of genes commonly downregulated in ISCs of Lgr5 KOs vs Lgr5 HEs at E16.5 and Lgr5 adult vs E18.5 HEs. RPKM: reads per kilobase of transcript per million mapped reads. Below: GeneOntology analysis of downregulated genes identified in the Epithelial Mesenchymal Transition Gene Set (Hallmark MSigDB collection). Biological replicates for RNAseq experiments on ISC Lgr5-DTReGFP E16.5 independent embryonic pools, each obtained from independent litters (n= 2 HE, 2 KO); Lgr5-DTReGFP E18.5 individual embryos (n=2 HE) and Lgr5-DTReGFP adult individual animals (n=2 HE); Lgr5-Cre/flox adult individual animals (n= 2 HE, 3 cKO). Data are represented as means ± sem (C).",
    "ncbi_link": "eGFP: 
Cre: 2777477
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Expression profile of Col1a1, Zeb2 and Cxcl10 genes detected by RNAscope in embryonic and adult intestines. Insets with higher magnification are depicted on the right of each corresponding picture, boundaries between epithelium and mesenchyme are shown with dotted lines and arrows point to epithelial expression.",
    "ncbi_link": "Col1a1: 12842
Cxcl10: 15945
Zeb2: 24136"
  },
  {
    "caption": "Expression of Axin2, Lgr5, Lgr4, Rspo1, Rspo2, Rspo3 and Rspo4 genes was analyzed on E15, E16.5 and adult stages by RNAscope. Arrows evidence expressing cells.",
    "ncbi_link": "Axin2: 12006
Lgr4: 107515
Lgr5: 14160
Rspo1: 192199
Rspo2: 239405
Rspo3: 72780
Rspo4: 228770"
  },
  {
    "caption": "Representative pictures showing the influence of mouse Rspondin type and concentration on growth of replated Lgr5-DTReGFP WT and Lgr5 KO organoids after 4 days of culture. Arrows show alive elements and arrow heads dead elements.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Heatmap showing the impact of Rspondin type and concentration (ng/ml) on relative Wnt target gene expression (list from the Sansom APC data set) in Lgr5-DTReGFP WT and KO organoids analyzed by RNAseq (n= 3 WT and 2 organoid culture samples, each originating from a given embryo).",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Gene expression analysis by qRT-PCR of stem cell markers in Lgr5-DTREeGFP WT and KO organoids after 5 days of culture (expression relative to reference genes). Each symbol indicates the value for an organoid culture originated from a given embryo.",
    "ncbi_link": "EeGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "Immunofluorescence showing Olfm4+ve cells in Lgr5-DTReGFP WT and KO organoids cultured in Rspo2 conditions. Epithelium is delineated with b-catenin and nuclei counterstained with DAPI (Merge). Insets: white arrowheads evidence Olfm4+ve cells concentrated in organoid protrusions. Quantification of Olfm4+ve area with respect to the total epithelial area. Each symbol indicates the value for an organoid culture originating from a given embryo.",
    "ncbi_link": "eGFP: 
DTR: 1839
Lgr5: 14160"
  },
  {
    "caption": "A-D J-Lat 8.4 cells were mock-treated or treated with increasing concentrations of 5-AzadC or 5-AzaC. At 72 h post-treatment; and initiated (primers TAR) or elongated (primers tat) transcripts were quantified by RT-qPCR (D).",
    "ncbi_link": "tat: 155871"
  },
  {
    "caption": "E J-Lat 8.4 cells were mock-treated or treated with 5-AzadC (400nM) or TNFα (10ng/ml) as positive control. At 24 h, 48 h or 72 h post-treatment, initiated (primers TAR) or elongated (primers tat) transcripts were quantified by RT-qPCR.",
    "ncbi_link": "tat: 155871"
  },
  {
    "caption": "A-F J-Lat 8.4 (A, C, E) and 15.4 (B, D, F) cell lines were mock-treated or treated with 5-AzadC. At 48 h post-treatment, HDACIs were then added for 24 h. At 72 h 5-AzadC post-treatment samples were harvested and analysed as follows: initiated (primers TAR) or elongated (primers tat) transcripts were quantified by RT-qPCR and results were normalized using the β-actin gene primers and are presented as histograms representing fold-inductions compared to the mock-treated condition (E and F). Means and standard errors of the means from three independent biological duplicates (n=6) are indicated. The result obtained with mock-treated cells was arbitrarily set at a value of 1 (E, F).",
    "ncbi_link": "β-actin: 
tat: 155871"
  },
  {
    "caption": "A. Representative confocal micrographs of HeLa cells transfected with a non-targeting siRNA pool (siNT - 40 nM) or a BNIP3L siRNA SMARTpool (siBNIP3L - 40 nM), infected or not (NI) with B. abortus 544 GFP (Red) for 48 h, then fixed and immunostained for BNIP3L (Alexa Fluor 568 - Magenta) and TOMM20 (Alexa Fluor 633 - Green). DNA was stained with Hoechst 33258 (Blue). B.,C. Quantification of the mitochondrial population morphology by assessing the AR (B) and EBR (C) of the mitochondria of HeLa cells from micrographs shown in (A). Data are presented as means ± SD from n=3 (biological replicates) independent experiments (the numbers indicated in the columns represent the number of cells analysed per condition). Statistical analyses were performed using a multiple Mann-Whitney test followed by a Holm-Šidàk's multiple comparisons test; asterisks indicate significant differences compared to the control (NI); *: p <0.05; **: p <0.01; hashtags indicate significant differences compared to the infected condition transfected with a siNT; #: p <0.05.",
    "ncbi_link": "BNIP3L: 665"
  },
  {
    "caption": "D. Representative confocal micrographs of HeLa cells transfected with a FIS1-GFP(Green)-mCherry(Magenta) expression construct, infected or not (NI) with B. abortus 544 for 48 h while being transfected with a non-targeting siRNA pool (siNT - 40 nM) or a BNIP3L siRNA SMARTpool (siBNIP3L - 40 nM), then fixed and immunostained for B. abortus LPS (Alexa Fluor 633 - Red). DNA was stained with Hoechst 33258 (Blue). Arrows indicate FIS1-mCherry-positive-GFP-negative punctae. Scale bars: 20 µm. E. Quantification of the number of FIS1-mCherry-positive-GFP-negative punctae per cell of HeLa cells from micrographs t shown in (D). Data are presented as means ± SD from n=3 (biological replicates) independent experiments (the numbers indicated in the columns represent the number of cells analysed per condition). Statistical analyses were performed using a two-way ANOVA followed by a Šidàk's multiple comparisons test; asterisks indicate significant differences compared to the control (NI); ns: not significant; **: p <0.01; hashtags indicate significant differences compared to the infected condition transfected with a siNT; #: p <0.05.",
    "ncbi_link": "BNIP3L: 665"
  },
  {
    "caption": "A. Representative confocal micrographs of HeLa cells infected with B. abortus 544 GFP (Green) and transfected with a non-targeting siRNA pool (siNT - 40 nM) or a BNIP3L siRNA SMARTpool (siBNIP3L - 40 nM) for 48 h, then incubated under reinfection-permissive conditions for 24 h before analysis at 72 h pi. Cells were fixed and DNA was stained with Hoechst 33258 (Blue). Arrows indicate reinfected cells. B. Quantification of the percentages of reinfection foci per infected cell at 72 h pi of HeLa cells from micrographs shown in (A). Data are presented as means ± SD from n=3 (biological replicates) independent experiments (the numbers indicated in the columns represent the number of cells analysed per condition). Statistical analyses were performed using an unpaired two-tailed Student's t-test; **: p <0.01 (p = 0.0032). C. CFU assay expressing Log (CFU/ml) from the supernatant of HeLa cells infected with B. abortus 544 GFP (Green) and transfected with a non-targeting siRNA pool (siNT - 40 nM) or a BNIP3L siRNA SMARTpool (siBNIP3L - 40 nM) for 48 h, then incubated under reinfection-permissive conditions for 24 h before collecting the supernatant at 72 h pi for analysis. Data are presented as means ± SD from n=5 (biological replicates) independent experiments; Statistical analyses were performed using an unpaired two-tailed Student's t-test; (p = 0.0042).",
    "ncbi_link": "BNIP3L: 665"
  },
  {
    "caption": "D. Representative confocal micrographs of HeLa cells infected with B. abortus 544 GFP (Red) and transfected with a non-targeting siRNA pool (siNT - 40 nM) or a BNIP3L siRNA SMARTpool (siBNIP3L - 40 nM) for 72 h pi, then fixed and immunostained for LAMP-1 (Alexa Fluor 568 - Green). DNA was stained with Hoechst 33258 (Blue). Arrows indicate LAMP-1-positive BCVs (aBCVs). Scale bars: 20 µm. E. Quantification of the number of LAMP-1-positive BCVs (aBCVs) per infected HeLa cells from micrographs shown in (E). Data are presented as means ± SD from n=3 (biological replicates) independent experiments (the numbers indicated in the columns represent the number of cells analysed per condition). Statistical analyses were performed using an unpaired two-tailed Student's t-test; *: p <0.05 (p = 0.0117).",
    "ncbi_link": "BNIP3L: 665"
  },
  {
    "caption": "(A) A boxplot showing log2 TPM values of HSPA5 gene expression compared between tumors and matched normal samples across 23 tumor types from TCGA with normal tissue data available. The boxplot indicates the median (central band) and the interquartile range (boxes) of the expression value and whiskers indicates values that outside of the middle 50% (interquartile). The barplot on the top shows the number of normal tissue samples for each corresponding tumor type. Asterisks indicate significant differences by student's t-test after Benjamini-Hochberg multiple testing correction (FDR < 0.05).",
    "ncbi_link": "HSPA5: 3309"
  },
  {
    "caption": "(B) Analysis and quantification of Xbp1 splicing in DLD1 and SKOV3 cells treated with varying concentrations of Reversine (Rv) for 12, 24, 48, and 72 hours. Thapsigargin  (Tg) is shown as positive control.",
    "ncbi_link": "Xbp1: 7494"
  },
  {
    "caption": "(D)  Xbp1 splicing in B16 melanoma cells and eight B16:MEF fused clonal cell lines.",
    "ncbi_link": "Xbp1: 22433"
  },
  {
    "caption": "(E) Detection of mRNA  expression (by  RT-PCR) of UPR-associated genes (Ern1, Af4, Ddit3 and Atf6) in tumor cells treated with Reversine  (Rv) at 4µM (DLD1  cells) or 0.5µM (SKOV3  cells) for 6 hours. Data points refer to triplicate samples collected at the same time point, run in duplicate, and expressed as means ± SD.",
    "ncbi_link": "Af4: 468
Atf6: 22926
Ddit3: 1649
Ern1: 2081"
  },
  {
    "caption": "(A)  Xbp1 splicing analysis (left panel) and quantification (right panel) of bone marrow-derived macrophages (BMDM) cultured in conditioned medium (CM) of Rv-treated  DLD1 and SKOV3  cells or respective control medium (culture medium of cancer cells not treated with Rv), and CM of fused B16 melanoma  cells or their nonfused parental cells.",
    "ncbi_link": "Xbp1: 7494"
  },
  {
    "caption": "(B, C) mRNA expression (RT-PCR) of Il6 (B) and Arg1 (C) in BMDM  cultured in the CM of  Rv-treated  SKOV3  cells (0.5µM for 3 days) or control cells, and CM of fused B16 cells or their nonfused parental cells. Data points refer to triplicate experiments expressed as means ± SD.",
    "ncbi_link": "Arg1: 383
Il6: 3569"
  },
  {
    "caption": "(a) Mouse fibroblasts knockeddown for LAMP-2A and transfected with KFERQ-PS-CFP2 were photoconverted and maintained in media supplemented (+) or not (−) with serum for 16 h. Representative images of cells also immunostained for LAMP-1 are shown.",
    "ncbi_link": "LAMP-2A: 16784"
  },
  {
    "caption": "(A) Lung cancer cells PC-9, prostate cancer cells 22RV1, bladder cancer cells UMUC3, breast cancer cells MCF-7, colonic adenoma-derived non-cancerous cells AA/C1 (aka C1) and AA/C1/SB (aka SB), or cancerous cells AA/C1/SB/10C (aka 10C) were incubated with wild-type F. nucleatum 12230 (Fn), the fadA-deletion mutant US1 (US1), or E. coli DH5α (E. coli) at multiplicity of infection (MOI) of 1,000:1. Cells numbers are mean values ± SEM. The experiment was performed in triplicates and repeated three times. **p<0.01, ***p<0.001, compared to untreated controls; #p<0.05, ### p<0.001, compared to US1-treated cells (two-way ANOVA).",
    "ncbi_link": "fadA: 31730396"
  },
  {
    "caption": "(B) Attachment (left panel) and invasion (right panel) of wild-type F. nucleatum 12230 (Fn) to the non-cancerous SB cells, either untreated or transfected with antisense or sense ANXA1, and to the cancerous 10C cells, either untreated or transfected with control or ANXA1- or CDH1-specific siRNA or both (MOI 50:1). F. nucleatum attachment and invasion to the untreated SB cells were designated as 100%, respectively; all other values were expressed as relative to those obtained with untreated SB. Data are mean values ± SEM. The experiment was performed in triplicates and repeated four times. *p<0.05, **p<0.01 and ***p<0.001 (one-way ANOVA).",
    "ncbi_link": "ANXA1: 
ANXA1: 301
CDH1: 999"
  },
  {
    "caption": "(C) Left panel: qPCR analysis of Villin1 (VIL1) mRNA levels in 10C cells treated with control siRNA or VIL1-specific siRNA, demonstrating knocking down of Villin1. Right panel: attachment of F. nucleatum 12230 to 10C cells treated with control siRNA or VIL1-specific siRNA. Data are mean values ± SD. The experiment was performed in triplicates and repeated twice. *p<0.05 (student's t-test).",
    "ncbi_link": "VIL1: 7429
Villin1: 7429"
  },
  {
    "caption": "Relationship between ANXA1 mRNA expression levels and disease-free survival (DFS) in colon cancer patients. The relationship between ANXA1 mRNA expression levels and DFS was investigated in a database of 466 primary colon carcinomas, assembled by pooling four independent gene-expression array datasets from the NCBI-GEO online repository (GSE14333, GSE17538, GSE31595, GSE37892) The association between ANXA1 expression levels and DFS was tested using Kaplan-Meier survival curves, after patient stratification in groups with high, medium and low ANXA1 expression, using three different methods: (A) based on the median of ANXA1 mRNA expression levels (high 50% vs. low 50%); (B) based on the quartile distribution of ANXA1 mRNA expression levels (high 25% vs. middle 50% vs. low 25%); and (C) based on ANXA1 mRNA expression thresholds calculated using the StepMiner algorithm (low vs. high) Overall, high ANXA1 mRNA expression levels were associated with a statistically significant reduction in DFS (p<0.001, log-rank test), irrespective of the method used for the stratification. Differences in ANXA1 mRNA expression levels did not appear to correlate with differences in each tumor's relative content of epithelial cells in the analyzed biospecimens (i.e. tumor cell density) as revealed by the lack of visual correlations with the epithelial cell marker Desmoplakin (DSP).",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(A) Real-time qPCR analysis of ANXA1 expression using mRNA extracted from the non-cancerous SB, cancerous 10C, and human CRC cell lines HCT116, DLD1 and RKO, each grown to 50% or 100% confluency. All results were normalized to the ANXA1 mRNA levels in SB cells of 100% confluency, which was designated as 1. Data are mean values ± SEM. The experiment was performed in triplicates and repeated twice. **p<0.01 and ***p<0.001 (student's t-test).",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(C) Cell proliferation assay of adenoma-derived non-cancerous SB and cancerous 10C and human CRC cell lines HCT116, DLD1, SW480, HT29 and RKO either untreated (black lines) or following treatment with control siRNA (gray lines) or ANXA1-specific siRNA (green lines). Data are mean values ± SEM. The experiment was performed in triplicates and repeated three times. *p<0.05, ** p<0.01 and *** p<0.001, compared to the untreated cells (two-way ANOVA).",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(D) Cell proliferation assay of SB (left panel) and RKO (right panel) cells transfected with ANXA1 (red line), as compared to the control cells (black lines). Data are mean values ± SEM. The experiment was performed in triplicates and repeated three times. *p<0.05, **p<0.01 and ***p<0.001 (two-way ANOVA).",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(E) Xenografted tumor growth in nude mice following subcutaneous and bilateral inoculation of HCT116 cells transfected with control siRNA or ANXA1-specific siRNA. The tumor volumes were measured after 7 days post injection (left panel, n=4). For each mouse, the tumor resulting from ANXA1-specific siRNA treated cells was normalized to that from control siRNA-treated cells, which was designated 100%. The line represents the average. *p<0.05 (paired t-test). The individual tumor pairs are shown on the right panel: top, tumors arising from control siRNA treated cells; bottom, tumors arising from ANXA1-specific siRNA treated cells.",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(A) Real-time qPCR analysis of ANXA1 mRNA levels in SB, 10C, HCT116 and DLD1 cells incubated with wild-type F. nucleatum 12230 (Fn) or fadA-deletion mutant US1 (US1) at MOI of 50:1 for the indicated time periods. The results were normalized to those obtained with untreated cells and were the mean of 3 independent experiments each performed in triplicates. *p<0.05, **p<0.01 and ***p<0.001 (two-way ANOVA).",
    "ncbi_link": "ANXA1: 301
fadA: 31730396"
  },
  {
    "caption": "(C) Flow cytometry analysis of Annexin A1 in 10C cells transfected with control siRNA (dotted black line) or CDH1-specific siRNA (dotted red line) followed by no treatment, or incubation with BSA (1000 µg/ml) or FadAc (1000 µg/ml) for 1 hr. C, untreated control. Data are mean values ± SD. The experiment was performed in triplicates and repeated twice. ***p<0.001 (two-way ANOVA).",
    "ncbi_link": "CDH1: 999"
  },
  {
    "caption": "Flow cytometry analysis of SB (A), 10C (B), DLD1 (C) and HCT116 (D) cells incubated with CFSE-labeled F. nucleatum 12230 (Fn) or its fadA-deletion mutant US1 (US1) at MOI of 10-20:1 for the indicated time and immuno-stained with anti-Annexin A1 antibodies. Shown on the top panels are the density plots. x-axis, CFSE-labeled F. nucleatum or US1 (CFSE-Fn); y-axis, Annexin A1 (ANXA1). Shown on the bottom panels are the percentages of Annexin A1-positive (solid bars) or negative (clear bars) cells bound by F. nucleatum or US1 out of the total number of cells analyzed. Data are mean values ± SD. The experiments were performed in triplicates and repeated 2-3 times. *p<0.05, **p<0.01, ***p<0.001 (two-way ANOVA).",
    "ncbi_link": "fadA: 31730396"
  },
  {
    "caption": "(A) Colorectal tumors generated in Apcmin/+ mice following treatment with PBS, E. coli DH5α (E. coli), fadA-deletion mutant US1 (US1) or F. nucleatum 12230 (Fn). Each symbol represents one mouse. Horizontal lines represent mean values. Representative tumors formed in the mouse colon are shown on the right, pointed by blue arrows on the right. *p<0.05, **p<0.01 (one-way ANOVA).",
    "ncbi_link": "Apc: 11789
fadA: 31730396"
  },
  {
    "caption": "(B) ANXA1 mRNA levels in Apcmin/+ mouse colonic tumors and normal colonic tissues as measured by real-time qPCR. Each symbol represents one mouse. Horizontal lines represent mean values. *p<0.05, **p<0.01 (two-way ANOVA).",
    "ncbi_link": "ANXA1: 301
Apc: 11789"
  },
  {
    "caption": "(C) Positive correlation between fadA gene copy numbers (x-axis) and ANXA1 mRNA levels (y- axis) in F. nucleatum-induced Apcmin/+ mouse colonic tumors (n=34; Pearson's correlation). Each dot represents the average of qPCR results performed in duplicates",
    "ncbi_link": "ANXA1: 301
Apc: 11789
fadA: 31730396"
  },
  {
    "caption": "(D) Abundance of fadA in the paired normal and adenocarcinoma tissues from human CRC patients (n=18) expressed as ratio of fadA over total 16S rRNA genes determined by qPCR. Each symbol shows the average of duplicate qPCR results from one patient. Horizontal lines represent mean values. **p<0.01 (paired t-test).",
    "ncbi_link": "16S rRNA: 
fadA: 31730396"
  },
  {
    "caption": "(E) ANXA1 mRNA levels in paired normal and adenocarcinoma tissues from CRC patients (n=18). Each symbol shows the average of duplicate qPCR results from one patient. Horizontal lines represent mean values. **p<0.01 (paired t-test).",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(F) Positive correlation between fadA gene copy numbers (x-axis) and ANXA1 mRNA levels (y-axis) in human colorectal adenocarcinoma tissues (n=18; Pearson's correlation). Each dot represents the average of qPCR results performed in duplicates.",
    "ncbi_link": "ANXA1: 301
fadA: 31730396"
  },
  {
    "caption": "(A) Flow cytometry analysis of β-catenin expression in 10C, HCT116 and DLD1 cells following transfection with control siRNA (clear bars) or ANXA1-specific siRNA (solid bars) and incubation with F. nucleatum 12230 at MOI of ~20:1 for indicated time periods. The geometric means of cells treated with control siRNA at time 0 was designated as 1. Data are mean values ± SD. The experiment was performed in duplicates or triplicates and repeated 1-3 times. **p<0.01, *** p<0.001 (two-way ANOVA).",
    "ncbi_link": "ANXA1: 301
β-catenin: 1499"
  },
  {
    "caption": "(B) Immuno-staining of β-catenin in 10C cells following transfection with control siRNA or ANXA1-specific siRNA and incubation with F. nucleatum 12230 (Fn) at MOI of ~100:1 for 2 hrs. β-catenin was stained with Alexa Fluor®680 (red) and the nuclei with DAPI (blue). The images were captured with confocal microscope at 800x magnification. -, no bacteria added. Note the increased expression of β-catenin and its nucleus translocation in response to F. nucleatum in control siRNA-treated cells, but not in ANXA1 siRNA-treated cells. The experiment was repeated twice. Scale bar, 200 nm.",
    "ncbi_link": "ANXA1: 301"
  },
  {
    "caption": "(C) Real-time qPCR analysis of CCND1 expression using mRNA extracted from the cancerous 10C, and human CRC cells HCT116 and RKO, each grown to 50% or 100% confluency. Data are mean values ± SEM. The experiment was performed in triplicates and repeated twice. *p<0.05, ***p<0.001 (student's t-test).",
    "ncbi_link": "CCND1: 595"
  },
  {
    "caption": "(D) Western-blot analysis of Cyclin D1, Annexin A1, and β-actin in RKO cells transfected with control vector or ANXA1. Induction of Cyclin D1 was observed in response to increased Annexin A1. The experiment was repeated twice.",
    "ncbi_link": "ANXA1: "
  },
  {
    "caption": "(F) Movements of KIF1A-EGFP and KIF1A(E239K)-EGFP expressed in KIF1A knockdown DRG and the scrambled control. White scale bar, 1 μm. (G) Anterograde velocities of the indicated genotypes calculated from the kymograph slopes. Data are shown as mean and SD. KD+KIF1A-EGFP, n = 29; KD+KIF1A(E239K)-EGFP, n = 32; scrambled+KIF1A-EGFP, n = 44; scrambled+KIF1A(E239K)-EGFP, n = 42 from three independent cultures. ns, p = 0.3329; **, p < 0.01; ****, p < 0.0001; Unpaired t test.",
    "ncbi_link": "EGFP: 
KIF1A: 16560"
  },
  {
    "caption": "(F) Rate constants (kobs) determined for the reaction of mant-ATP with nucleotide-free KIF1A(WT) and KIF1A(E239K) were plotted against concentration of mant-ATP. Data are represented as the mean ± SD. The data from three independent measurements were analysed.",
    "ncbi_link": "KIF1A: 16560"
  },
  {
    "caption": "(A) Western blot of Beclin‐1 and FACS profiles following siRNA treatment in HeLa cells and cells stably expressing a HA‐Beclin‐1 construct resistant to the siRNA targeting endogenous Beclin‐1.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(C,D) Quantification of cells in mitosis (C) and quantification of each step of mitosis (D) by H3Ser10P staining for Control and Beclin‐1 siRNA‐treated cells. Error bars represent standard deviations (s.d.) (n=number of counted cells) calculated on three independent experiments. Two and three asterisks indicate significant results (P=0.0028 and P=0.0006, respectively).",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(E) Knockdown of Beclin‐1 increases the number of mitotic cells with misaligned chromosomes. siRNA‐treated HeLa cells were fixed in PFA, immunolabelled for α‐tubulin (green) and stained with DAPI (blue). White arrows indicate misaligned chromosomes. Quantification of cells with misaligned chromosomes is shown at the right (n=number of counted cells). Three asterisks indicate significant results (P=0.0001). Scale bar, 10 μm. DAPI, 4′,6‐diamidino‐2‐phenylindole; HA, haemagglutinin; PFA, paraformaldehyde; siRNA, small interfering RNA.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "Beclin‐1 depletion prolongs prometaphase by delaying chromosome congression. (A-H) Time‐lapse films of HeLa cells stably expressing YFP‐α‐tubulin and H2B‐Cherry and treated with the indicated siRNA. The pictures are acquired every 10 min. Time lapse starts at nuclear envelope breakdown. (A) Mitosis in control cells. (B) Western blot of whole‐cell lysates from Control, Beclin‐1 and Beclin‐1+Mad2 siRNA‐treated cells. (C-E) Three different classes of mitotic progression were observed upon Beclin‐1 depletion. Higher magnification of lagging chromatids in the anaphase of Beclin‐1‐depleted cells is shown on the right of (D).",
    "ncbi_link": "Beclin‐1: 8678
Mad2: 10459///4085"
  },
  {
    "caption": "(F) The prometaphase delay is dependent on MAD2 and the spindle checkpoint. Cells treated simultaneously with siRNA targeting MAD2 and Beclin‐1 rapidly exit mitosis. (G) Average duration of mitosis in different classes of Beclin‐1‐depleted cells, compared to control and MAD2 depletions. n=number of counted cells in three independent experiments. Error bars on graphs represent s.d.",
    "ncbi_link": "Beclin‐1: 8678
MAD2: 10459///4085"
  },
  {
    "caption": "(H) The frequency of the different Beclin‐1 phenotypes depended on the efficiency of Beclin‐1 knockdown. Mitotic progression in cells treated with increasing concentrations of Beclin‐1 siRNA was followed by video‐microscopy. Left panel: western blot of Beclin‐1 upon RNAi treatment; right panel: quantification of the appearance of the three different mitotic progression patterns, that is, prolonged mitosis with normal anaphase (as C), with lagging chromatids (as D) and mitotic exit without clear anaphase (as E) upon increased Beclin‐1 knockdown experiments. NEB, nuclear envelop breakdown; RNAi, RNA interference; siRNA, small interfering RNA; YFP, yellow fluorescent protein.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(A) Inter‐kinetochore distance is reduced in unaligned chromosomes of Beclin‐1‐depleted cells. The distance between each kinetochore pair was quantified in siRNA‐treated and control cells treated with nocodazole for 3 h before fixation. Cells were stained with anti‐CREST antibody and DAPI. Quantification of the distance between kinetochore pairs (indicated by coloured bars) is reported at the bottom and done on sister kinetochores present in the same focal plane. One asterisk indicates significant result (P=0.0365). Graphs represent three independent experiments (error bars=s.d.).",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(B) Depletion of Beclin‐1 leads to defects in K‐MT attachment. siRNA‐treated cells were cooled on ice before fixation to reveal stable k‐fibres and then stained with anti‐α‐tubulin (red) and anti‐CREST (green) antibodies. Numbers point to magnified areas and indicate the mode of attachment of k‐fibres to kinetochores (1, bi‐oriented; 2, unattached; 3, mono‐oriented kinetochores). Scale bar, 10 μm. DAPI, 4′,6‐diamidino‐2‐phenylindole; NS, not significant; siRNA, small interfering RNA.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(G) Western blot of whole‐cell lysates from control and Beclin‐1 siRNA‐treated cells. siRNA, small interfering RNA.",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(C) Zwint‐1 levels do not change in Beclin‐1‐depleted cells. Cells were treated with nocodazole before fixation. On the right, magnified individual kinetochore pairs stained for Zwint‐1 (red) and CREST (green), and quantification of Zwint‐1 levels normalized to CREST signal from three independent experiments (error bars=s.d.).",
    "ncbi_link": "Beclin‐1: 8678"
  },
  {
    "caption": "(H) Beclin‐1 localization close to the kinetochore does not depend on the ZW10 protein. Cells treated with Control, Beclin‐1 and ZW10 siRNA were pre‐extracted and fixed before labelling with Beclin‐1 (green), CREST (blue) and ZW10 (red) antibodies. DNA was visualized with DAPI. (C-H) Scale bar, 10 μm. DAPI, 4′,6‐diamidino‐2‐phenylindole; DNA, deoxyribonucleic acid; GFP, green fluorescent protein; GST, glutathione S‐transferase; HA, haemagglutinin.",
    "ncbi_link": "Beclin‐1: 8678
ZW10: 9183"
  },
  {
    "caption": "F.  Proliferation  curves of factor-independent TF-1 TpoR CALRdel61 cells cultured with 2, 10 or 20 µg/mL   4D7 or 20 µg/mL of control IgG antibody (n=3 biological replicates). G Proliferation curves of factor-independent TF-1 TpoR CALRdel52 cells cultured with 10 or 20 µg/mL  4D7  or 20 µg/mL of control IgG antibody (n=3 biological replicates). Data information: bars represent standard error of the mean summarizing 3 biological replicates performed in triplicate, with a one-way ANOVA with Bonferroni correction used to determine statistical significance.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "B. Similar experiment using TPO-independent TF-1 TpoR CALRdel61 cells. C. Similar experiment using TPO-independent  TF-1 TpoR CALRdel52 cells at 8 hours. D. Similar experiment using PBMNCs from CALRdel52 PMF  primary cells at 8 hours. Additionally, cells were treated with 280 nM of ruxolitinib as a positive control.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "F. Western blot showing caspase 3  cleavage occurring within 24 hours of TPO  withdrawal in TPO  dependent  TF-1 TpoR cells. An increase in cleaved caspase 3 is observed after 48 hours of treatment with 20 µg/mL  4D7 in TF-1 TpoR CALRdel61 and TF-1 TpoR CALRdel52 cells.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "G. Western blot of  TpoR immunoprecipitation under non-reducing conditions showing associated CALR  50 kDa monomers and 100 kDa dimers (red arrowheads) present only in TF-1 TpoR CALRdel61 disrupted by 8-hour treatment with 20 µg/mL 4D7 but not  PBS  or 20 µg/mL IgG. CALR  monomers & dimers are detectable by polyclonal anti-wild type CALR or anti-mutant CALR  monoclonal antibodies. Red arrowheads, detected mutant CALR  protein; brown arrowheads, detected wildtype CALR protein, asterisk, non-specific bands.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "B. Graph showing the decreased fold change of CD41+CD61+  megakaryocytes cultured in  4D7  compared to IgG. FACS-sorted CD34+ from myelofibrosis patients with  CALR  or JAK2  mutation were cultured over 12 days without TPO in the presence of  SCF, IL-6  and IL-9. Black columns show JAK2V617F mutation positive samples (n= 4 technical replicates of samples from different patients). Data information: Unpaired students t-test used to determine statistical significance Bars represent standard deviations *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "ncbi_link": "CALR: 811
JAK2: 3717"
  },
  {
    "caption": "C. Number of CD41+ megakaryocytes  derived from isolated  CD34+ progenitors from myelofibrosis patients. Number of  CD41/CD61+ cells counted on day 12 using  trypan blue  exclusion (n=1 technical replicate). D. Summary of fold change reduction of  CD41/CD61+ megakaryocytes by 4D7 in all tested CALR  mutated patient  samples compared to CALR wild type, normalised to IgG (n=11 samples from different patients, with 4 technical replicates per sample). Data information: Bars represent standard error of means Unpaired students t-test used to determine statistical significance *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "ncbi_link": "CALR: 811"
  },
  {
    "caption": "E Number of  CD41+ megakaryocyte  colonies from patient  samples after  4D7  treatment. CD34+ from  patients with myelofibrosis  with  CALRdel52 or CALRins5 were plated on  collagen-based matrix in presence of 20 µg/mL  4D7  or IgG control (n=3 biological replicates). Data information: Unpaired students t-test used to determine statistical significance Bars represent standard deviations *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "ncbi_link": "CALR: 811"
  },
  {
    "caption": "F. Representative micrographs showing CD41+ colonies in pink and CD41- colonies in blue after treatment with  4D7 or IgG  at 100 X or 40X magnification. Scale bar indicates 100µm. G. Summary of fold change reduction of CD41+  megakaryocytes in CALR mutated samples cultured MegaCult treated with 4D7  compared to IgG (n= 4 biological replicates). Data information: Bars represent standard error of means Unpaired students t-test used to determine statistical significance *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "ncbi_link": "CALR: 811"
  },
  {
    "caption": "H. Number of  megakaryocyte colony forming units grouped according to colony cell number after  4D7   treatment in a mutant CALRins5 sample (n=3 biological replicates). Data information: Unpaired students t-test used to determine statistical significance Bars represent standard deviations *, P = 0.05 - 0.01, **, P = 0.01 - 0.001, ***, P = 0.001 - 0.0001, ****, P <0.0001, n.s, not significant.",
    "ncbi_link": "CALR: 811"
  },
  {
    "caption": "F. Western blot  showing signalling in ruxolitinib-resistant TF-1 TpoR CALRdel61 compared to ruxolitinib sensitive TF-1 TpoR CALRdel61 cells after treatment with 100nM  ruxolitinib for 16 hours or 30 minutes and blotted for phospho-STAT5, total STAT5, phospho-ERK, total ERK and  actin  as indicated. Ruxolitinib-sensitive  cells were non-viable after 16 hours of treatment.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "G. Comparison of  cell growth after DMSO, 20 µg/mL   4D7, IgG or 100 nM ruxolitinib  treatment over 4 days of ruxolitinib-resistant  TF-1 TpoR CALRdel61. Cells counted using Trypan Blue  exclusion (n=3 biological replicates with 3 technical replicates). H. Number of colonies observed from cells plated in MethoCult following 72 hours of treatment with DMSO, 20 µg/mL  4D7, IgG or 100nM ruxolitinib performed in ruxolitinib-resistant TF-1 TpoR CALRdel61 cells (n=3 biological replicates with 3 technical replicates). Data information: Error bars on represent standard deviation. All P values are unpaired Student's unpaired t-test.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "D. Kaplan-Meier survival  curve of bone marrow engraftment  model of TF-1 TpoR CALRdel61 cells showing improved survival of mice treated with 4D7   compared with IgG control commencing 1 week after tail vein injection (n=5 mice per treatment). Data information: For all survival  curves the log-rank Mantel-Cox test P value is shown.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "F. Kaplan-Meier survival curve of TF-1 TpoR CALRdel61 chloroma mice  treated with  4D7 or IgG until humane killing due to tumour diameter > 30 mm or ulceration. (n=3  mice  per treatment) G. Kaplan-Meier survival curve of NSG mice engrafted  with  ruxolitinib-resistant TF-1 TpoR CALRdel61 treated with 12.5 mg/kg  4D7  or IgG twice weekly (n=5 and 6 mice  for IgG and   4D7 respectively). Data information For all  survival curves  the log-rank Mantel-Cox test P value is shown.",
    "ncbi_link": "CALR: 811
TpoR: 4352"
  },
  {
    "caption": "DRiP labelling in GFP-NCL HeLa Kyoto cells that were either left untreated or treated with OP-puro (25 µM) for 2 h. Where indicated cells were allowed to recover in drug-free medium (control) or in presence of MG132 (10 µM) for 5 h. Scale bars: 5 µm. GFP-NCL HeLa Kyoto cells were treated as described in A, with the exception that a lower concentration of OP-puro was used (5 µM). The distribution of DRiPs and GFP-NCL was analyzed by STED super-resolution microscopy. Scale bars: 5 µm.",
    "ncbi_link": "GFP: 
NCL: 4691"
  },
  {
    "caption": "DRiP labelling in GFP-NCL HeLa Kyoto cells that were either left untreated or treated with HS at 42˚C and OP-puro (25 µM) for 2 h. Where indicated, cells were cotreated with CHX (50 μg/ml).",
    "ncbi_link": "GFP: 
NCL: 4691"
  },
  {
    "caption": "HSPA8 subcellular distribution and recruitment inside nucleoli following exposure to HS at 42˚C for 2 h, alone or combined with CHX, in GFP-NCL HeLa Kyoto cells.",
    "ncbi_link": "GFP: 
NCL: 4691"
  },
  {
    "caption": "HeLa cells were transfected with vectors encoding for GFP, GFP-GR50 or RPL23a-GFP. 24 hrs post-transfection cells were fixed and stained with Amylo-glo. The percentage of transfected cells with Amylo-Glo positive nucleoli is shown. Number of cells counted/condition: GFP, 412; RPL23a-GFP, 482; GFP-GR50, 359, in three independent experiments; statistical significance via One-way ANOVA; p < 10-7, ± s.e.m.",
    "ncbi_link": "GFP: 
GR50: 
RPL23a: 6147"
  },
  {
    "caption": "DRiPs, polyUb proteins (FK1) and PML labelling in HeLa cells treated with OP-puro (25 µM) and heat shock (HS) at 42˚C for 2 h; where indicated cycloheximide was also added (CHX; 50 μg/ml). Scale bars: 5 µm. Lower panel: STED super-resolution microscopy showing colocalization of DRiPs with PML-NBs in PML-GFP HeLa cells treated with a low concentration of OP-puro (5 µM) and heat shock (HS) at 42˚C for 2 h. PML-NBs were visualized using a PML specific antibody, followed by incubation with alexa fluor 647. For convenience the alexa fluor 647 signal is shown in green. Scale bars: 5 µm.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "STED super-resolution microscopy showing colocalization of endogenous polyUb proteins (FK1) and PML-NBs in PML-GFP HeLa cells treated with HS at 42˚C for 2 h. Scale bars: 5 µm.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "DRiPs, polyUb proteins (FK1) and PML labelling in HeLa cells treated with MG132 (10 µM) and OP-puro (25 µM) for 4 h; where indicated, cycloheximide was also added (CHX; 50 μg/ml). Asterisks (*) indicate nucleoli. Scale bars: 10 µm. Lower panel: STED super-resolution microscopy showing colocalization of DRiPs with PML-NBs in PML-GFP HeLa cells treated with a low concentration of OP-puro (5 µM) and MG132 (10 µM) for 4 hrs. Scale bars: 5 µm. Quantitation of cells shown in E. Number of cells counted/condition: 298 - 1713 in three independent experiments; statistical significance via One-way ANOVA; p ≤ 0.001, ± s.e.m.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "HeLa cells were lipofected with non-targeting siRNA control or a specific siRNA against PML. 72 h post-transfection, total proteins were extracted and expression levels of PML were analyzed by immunoblotting. TUBA4A was used as loading control.",
    "ncbi_link": "PML: 5371"
  },
  {
    "caption": "HeLa cells were lipofected with non-targeting siRNA control or a specific siRNA against PML. 72 h post-transfection, cells were treated with MG132 (10 µM) and OP-puro (25 µM) for 4 h. Left panel: automated quantitation of the number of PML-NBs/nucleus is reported. Statistical significance via 2‐tailed Student's t‐test. Cell number analyzed: 334 - 364; p < 10-10. Right panel: automated quantitation of the number of DRiP foci/nucleus. Cell number analyzed: 334 - 364; p < 10-10. Automated DRiP segmentation is based on azide signal.",
    "ncbi_link": "PML: 5371"
  },
  {
    "caption": "Immunoblotting on protein extracts from HeLa cells lipofected with non-targeting siRNA control or a specific siRNA against Ubc9. A dilution curve of the control sample is shown. TUBA4A was used as loading control. Quantitation of the number of PML-NBs/nucleus from cells treated as described in (D). Statistical significance via 2‐tailed Student's t‐test. Cell number analyzed: 192 - 430; p < 10-10. Automated PML-NB segmentation is based on PML signal.",
    "ncbi_link": "Ubc9: 7329"
  },
  {
    "caption": "Cells lipofected for 72 h with non-targeting siRNA control or a specific siRNA against Ubc9 were treated with MG132 (10 µM) and OP-puro (25 µM) for 4 h. Automated quantitation of the number of PML-NBs/nucleus is reported. Statistical significance via 2‐tailed Student's t‐test. Cell number analyzed: 151 - 225; p < 10-10 (see panel G).",
    "ncbi_link": "Ubc9: 7329"
  },
  {
    "caption": "Quantitation of the number of PML-NBs/nucleus from cells treated as described in (D). Statistical significance via 2‐tailed Student's t‐test. Cell number analyzed: 192 - 430; p < 10-10. Automated PML-NB segmentation is based on PML signal. Representative pictures showing that Ubc9-depleted cells cannot efficiently induce the self-assembly of PML-NBs upon treatment with MG132 (10 µM) and OP-puro (25 µM) for 4 h. Scale bars: 10 µm.",
    "ncbi_link": "Ubc9: 7329"
  },
  {
    "caption": "PolyUb protein (FK1) labelling in PML-GFP HeLa Kyoto cells that were either left untreated or treated with MG132 (10 µM) and OP-puro (25 µM) for 4 h. Cells were either immediately fixed or let to recover for 5 h in drug-free medium (Control), with VER (40 µM) or Eeyarestatin I (5 µM). Scale bars: 10 µm. Quantitation of the % of cells with polyUb (FK1) nuclear foci shown in (A). Number of cells counted/condition: 310 - 1258 in three independent experiments; statistical significance via One-way ANOVA; p = 0.0003 or 10-6, ± s.e.m.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "Amylo-Glo staining of PML-GFP HeLa Kyoto cells that were subjected to the following treatments: untreated (Control); MG132 (10 µM) and OP-puro (25 µM) for 4 h, alone or combined with CHX (50 μg/ml). Where indicated cells were allowed to recover for 5 hrs in drug-free medium (Control) or with VER (40 µM). Confocal images showing Amylo-Glo and PML-GFP. Scale bars: 5 µm.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "Amylo-Glo staining of PML-GFP HeLa Kyoto cells that were subjected to heat shock (HS) at 42˚C for 2 hrs. Confocal images showing Amylo-Glo and PML-GFP. Scale bars: 5 µm.",
    "ncbi_link": "GFP: 
PML: 5371"
  },
  {
    "caption": "PML-GFP HeLa Kyoto cells were lipofected with a cDNA encoding for mCherry-VHL. 24 h post-transfection, cells were left untreated or treated with MG132 (10 µM) and OP-puro (25 µM) for 4 h. Where indicated (OP-puro + MG132 + CHX), translation was inhibited during stress with cycloheximide (CHX; 50 μg/ml). In the lower panel, cells were allowed to recover for 5 h in drug-free medium (Control), or with VER (40 µM). The subcellular distribution of PML-GFP and mCherry-VHL was studied by live-cell confocal imaging. Representative pictures are shown. Scale bars: 5 µm. Quantitation of the fluorescence intensity recovery after bleach of PML-GFP. PML-GFP HeLa Kyoto overexpressing mCherry-VHL for 24 h and treated as described in (A) were analyzed. The mean of 19-23 FRAP curves and the fitting curves are shown in black and red respectively. In gray, the SD is shown.",
    "ncbi_link": "GFP: 
mCherry: 
PML: 5371
VHL: 7428"
  },
  {
    "caption": "GFP-PSMA7 HeLa Kyoto cells were left untreated or treated as described in A. Cells were subjected to FRAP to analyze GFP-PSMA7 mobility. Quantitation of three populations of GFP-PSMA7 molecules is shown: fast moving, slow moving and immobile; statistical significance via One-way ANOVA; n = 12 - 14 ± SEM.",
    "ncbi_link": "GFP: 
PSMA7: 5688"
  },
  {
    "caption": "HeLa cells were lipofected with cDNAs encoding for HA-Ubiquitin, Flag-Ubiquitin or Flag-VCP 24 h post-transfection, cells were either left untreated or treated with MG132 (10 µM) and OP-puro (25 µM). Cells were processed for staining of HA, Flag and endogenous 53BP1. * indicates cells that do not express HA- or Flag-Ubiquitin and show no rescue of 53BP1 foci formation after stress. Scale bars: 20 µm. Quantitation of the % of cells with 53BP1 foci. Cells were treated as described in (C) and divided in three categories, based on the number of 53BP1 foci/nucleus: 0, 1-2 and > 3. Number of cells counted/condition: 710 - 938 in three independent experiments; statistical significance via One-way ANOVA; p < 0.01.",
    "ncbi_link": "Flag: 
HA: 
Ubiquitin: 
VCP: 7415"
  },
  {
    "caption": "(A) Representative immunofluorescence images of HeLa cells cultured on micropatterned surface of multiple geometries. Cells were transfected with 10 nM non-targeting control (siCtrl) or co-transfected with siRNAs targeting Sar1A and Sar1B. After 48 h, cells were trypsinized and 80,000 cells were seeded on micropatterned chips. Cells were allowed to attach for 3 h, stained with CellMask for 5 min and processed for microscopy. Scale bars: 5 µm (B) Quantification graph showing the percentage of cells failing to entirely cover the different geometries (described in A). Data derived from at least 100 cells from a set of three independent experiments. Error bars represent standard deviation. Asterisks (*) denote statistical significance (p-value < 0.05; chi-squared test).",
    "ncbi_link": "Sar1A: 56681
Sar1B: 51128"
  },
  {
    "caption": "(A) HeLa cells were transfected with 10 nM non-targeting control siRNA (siCtrl) or siRNAs targeting Rac1 (siRac1). After 72 h, cells were fixed and processed for immunostaining against Sec31A to label ERES. Representative confocal microscopy images are shown. (B) Quantification graph shows the number of ERES/cell in cells transfected with control siRNA (siCtrl) or siRNA against Rac1 (two siRNAs #1 and #2). Values are expressed as % of siCtrl. From three independent experiments, with >30 cells per condition were counted. (C) Representative immunofluorescence images showing ERES in HeLa cells treated with DMSO (Ctrl), Rac1 inhibitor NSC23766 (50 µM, 4 h), or NSC23766 washout (50 µM for 4h, then washout for 2h). (D) Graph shows the number of ERES per cell (displayed as % of Ctrl) derived from at least 30 cells per condition from three experiments.",
    "ncbi_link": "Rac1: 5879"
  },
  {
    "caption": "(G) The rate of ER-export was monitored using GFP-ManII-RUSH in HeLa cells after perturbation of Rac1 with siRNA (siRac1), or Rac1 inhibitor NSC23766, or a combination of both. Representative images show GFP-ManII-RUSH distribution in HeLa cells at indicated time points. (H) Quantification shows ratio of ManII fluorescence intensity within Golgi to outside Golgi region after addition of biotin at indicated time points. Between 76 - 104 cells were used for measurement of ManII intensity in 3 experiments.",
    "ncbi_link": "Rac1: 5879"
  },
  {
    "caption": "(H and I) siRNA mediated depletion of INF2 does not phenocopy Rac1 effect. HeLa cells were transfected with non-targeting control siRNA (siCtrl) or siRNA against INF2 (siINF2) for 72 h before processing cells immunostaining with Sec31A to quantify ERES. Representative images showing Sec31A-labelled ERES in HeLa cells (H), and quantification of ERES per cell presented as % of control (I). In total 137 cells (siCtrl) and 113 cells (siINF2) were used for ERES quantification from three independent experiments.",
    "ncbi_link": "INF2: 64423
Rac1: 5879"
  },
  {
    "caption": "(J and K) Knockdown of INF2 does not alter the kinetics of ER-to-Golgi transport. HeLa cells stably expressing ManII-RUSH were transfected with siRNAs as described in E, and the ER-to-Golgi transport of ManII-RUSH was followed by confocal microscopy (J). Representative images for indicated time points are shown. Scale bars, 5 µm. The ratio of ManII-RUSH within the Golgi to outside the Golgi was calculated for the indicated time points (K). Three independent experiments were performed and a total of 82 (siCtrl, 0 min), 72 (siINF2, 0 min) and 93 (siCtrl and siINF2, 20 min) were used for quantification.",
    "ncbi_link": "INF2: 64423"
  },
  {
    "caption": "(B) Representative immunofluorescence images of HeLa cells co-transfected with YFP(N)-Rac1 and Sar1-YFP(C) and immunostained with Sec31A. Rac1 and Sar1 form complexes at ERES in HeLa cells, which partially overlap with Sec31A. (C) Box plot showing the fraction of ERES that overlap with the Rac1-Sar1 complex (number of cells = 24, number of experiments = 4). Individual data points shown in the graph represent number of images. Whiskers indicate min-max range and central band indicates the median of all data.",
    "ncbi_link": "YFP: 
Rac1: 5879
Sar1: 56681"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. Body weight curve.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. Cumulative body weight.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. Fasting and fed blood glucose.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. Rectal temperature.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. Locomotor tolerance.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a standard diet (SD) or high-fat diet ( HFD) for 3 months. 24-h oxygen consumption. Respiratory exchange ratio (RER: VCO2/VO2). Energy expenditure.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a SD or HFD for 3 months. Blood glucose levels and area under curve (AUC) during the glucose tolerance test. Blood glucose levels and AUC during the insulin tolerance test.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a SD or HFD for 3 months. Glucose infusion rates (GIR). Glucose disposal rate (GDR). Hepatic glucose production (HGP).",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice were fed a SD or HFD for 3 months. Percentage of suppression of hepatic glucose production (HGP).",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/- mice Glucose infusion rates (GIR) during lipid infusion.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/-mice were fed a SD or a HFD for 3 months. Mice were treated with insulin (1 U/kg) or control (PBS) by intraperitoneal injection for 10 minutes; animals were killed and livers were collected. The expression of expression of phosphoenolpyruvate carboxykinase(PEPCK) and glucose-6- phosphatase(G6Pase) mRNA and protein.",
    "ncbi_link": "DOCK5: 68813
glucose-6- phosphatase: 14377
phosphoenolpyruvate carboxykinase: 18534"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/-mice were fed a SD or a HFD for 3 months. Mice were treated with insulin (1 U/kg) or control (PBS) by intraperitoneal injection for 10 minutes; animals were killed and livers were collected. Total and phosphorylated insulin receptor (InsR), IRS-1ser1101 and Akt.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male WT and DOCK5-/-mice were fed a SD or a HFD for 3 months. Mice were treated with insulin (1 U/kg) or control (PBS) by intraperitoneal injection for 10 minutes; animals were killed and livers were collected. Total and phosphorylated mTOR, S6K1, and the levels of Raptor and Rictor protein.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Hep1-6 cells were infected with pCDNA3.1-DOCK5 (DOCK5 +) or pCDNA3.1 (DOCK5-) for 48 h. mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. The mRNA and protein expression of PEPCK and G6Pase in Hep1-6 cells.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Hep1-6 cells were infected with pCDNA3.1-DOCK5 (DOCK5 +) or pCDNA3.1 (DOCK5-) for 48 h. - mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. Total and phosphorylated InsR, IRS-1Ser1101 and Akt in Hep1-6 cells.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Hep1-6 cells were infected with pCDNA3.1-DOCK5 (DOCK5 +) or pCDNA3.1 (DOCK5-) for 48 h. mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. Total and phosphorylated mTOR and S6K1, and the levels of Raptor and Rictor protein in Hep1-6 cells.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "MPHs isolated from WT and DOCK5-/- mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. The mRNA and protein expression of PEPCK and G6Pase in MPHs.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "MPHs isolated from WT and DOCK5-/- mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. Total and phosphorylated InsR, IRS-1Ser1101 and Akt in MPHs.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "MPHs isolated from WT and DOCK5-/- mice were incubated in control (GlcN-) or GlcN (GlcN+) medium for indicated times, followed with (Ins+) or without (Ins-) 100 nmol/L insulin stimulation for 20 min. Total and phosphorylated mTOR and S6K1, and the levels of Raptor and Rictor protein in MPHs.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Eight-week-old male Raptor flox/flox mice (Raptorflox/flox Cre+) were fed a HFD for 12 weeks and injected with AAV8-shDOCK5 ± AAV8-Cre or AAV8-GFP (at a dose of 3 × 1011 vg / 200 μL/ mouse) via the tail-vein 14 days prior to the in vivo study. Fasting and fed blood glucose 14 days post-infection.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "Eight-week-old male Raptor flox/flox mice (Raptorflox/flox Cre+) were fed a HFD for 12 weeks and injected with AAV8-shDOCK5 ± AAV8-Cre or AAV8-GFP (at a dose of 3 × 1011 vg / 200 μL/ mouse) via the tail-vein 14 days prior to the in vivo study. Blood glucose levels and AUC during glucose tolerance tests. Blood glucose levels and AUC during insulin tolerance tests. Glucose infusion rates (GIR). Glucose disposal rate (GDR). Hepatic glucose production (HGP). Percentage of suppression of hepatic glucose production (HGP).",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "Male Raptor flox/flox mice (8 weeks) were fed a HFD for 12 weeks and injected with AAV8- GFP or AAV8-shDOCK5 or AAV8-shDOCK5 + AAV8-Cre via the tail vein. The mRNA and protein expression of PEPCK and G6Pase in the liver.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "Male Raptor flox/flox mice (8 weeks) were fed a HFD for 12 weeks and injected with AAV8- GFP or AAV8-shDOCK5 or AAV8-shDOCK5 + AAV8-Cre via the tail vein. Total and phosphorylated InsR, IRS-1Ser1101 and Akt in the liver.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "Male Raptor flox/flox mice (8 weeks) were fed a HFD for 12 weeks and injected with AAV8- GFP or AAV8-shDOCK5 or AAV8-shDOCK5 + AAV8-Cre via the tail vein. The levels of DOCK5 and Raptor protein, and total and phosphorylated mTOR and S6K1 in the liver.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "MPHs from Raptor flox/flox mice were infected with Ad-GFP or Ad-shDOCK5 or Ad-shDOCK5 + Ad-Cre. The lysates were immunoblotted with indicated antibodies or β-actin. The expression of PEPCK and G6Pase mRNA and protein.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
G6Pase: 14377
PEPCK: 74551///18534
Raptor: 74370"
  },
  {
    "caption": "MPHs from Raptor flox/flox mice were infected with Ad-GFP or Ad-shDOCK5 or Ad-shDOCK5 + Ad-Cre. The lysates were immunoblotted with indicated antibodies or β-actin. Total and phosphorylated InsR, IRS-1Ser1101 and Akt.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "MPHs from Raptor flox/flox mice were infected with Ad-GFP or Ad-shDOCK5 or Ad-shDOCK5 + Ad-Cre. The lysates were immunoblotted with indicated antibodies or β-actin. The levels of DOCK5 and Raptor protein, and total and phosphorylated mTOR and S6K1.",
    "ncbi_link": "GFP: 
Cre: 2777477
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "Rac1 GEF activation in MPHs from WT and DOCK5-/- mice.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "SEW2871 treatment promotes Rac1 GEF activation and eliminates the influence of a DOCK5 deficiency on Raptor / S6K1 signaling in the mouse primary hepatocytes (MPHs) of DOCK5-/- mice.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "Total and phosphorylated mTOR and S6K1 and the level of Raptor protein expression in plasmids expressing a WT DOCK5 or mutant DOCK5 treated-Hep1-6 cells.",
    "ncbi_link": "DOCK5: 68813"
  },
  {
    "caption": "DOCK5 binding to Raptor fragments (445 - 887 aa) during transient expression in Hepa1-6 cells.",
    "ncbi_link": "Raptor: 74370"
  },
  {
    "caption": "The DOCK5 and Raptor binding sites were identified using mutant DOCK5 (DHR-2V1559A) and Raptor fragments (445 - 887 aa) based on a Co-IP assay. VA, mutant DOCK5 DHR-2; His, His-DHR-2.",
    "ncbi_link": "His: 
DOCK5: 68813
Raptor: 74370"
  },
  {
    "caption": "(D) COS7 cells were transfected for 24 h with nonsense or bag3 siRNA and treated with MG132 (25 μM, 12 h). Aggresomes were visualized by ubiquitinimmunostaining ( supplementary Fig S1D online). Diagram shows the percentage of aggresome‐positive cells.",
    "ncbi_link": "bag3: "
  },
  {
    "caption": "(H) COS7 cells transfected with BAG3 or empty vector were treated with either MG132 (25 μM, 18 h) or DMSO as a control. After MG132 wash out, cells were allowed to recover for 4, 24 and 48 h and 0.5% NP40‐soluble and ‐insoluble proteins were analysed by immunoblotting.",
    "ncbi_link": "BAG3: "
  },
  {
    "caption": "(A) GST pull‐down analysis as in Fig 1I, but performed in cells transfected for 36 h with full‐length FLAG‐BAG3 (I) or the BAG3 deletion mutants FLAG-(Δ421-498)-BAG3 (II), FLAG-BAG‐domain (III), and FLAG-PxxP-BAG‐domain (IV). Asterisk, nonspecific band.",
    "ncbi_link": "BAG3: "
  },
  {
    "caption": "(B) HEK cells were transfected for 18 h with SODG85R‐GFP, along with the indicated FLAG‐tagged BAG3 constructs (shown in A) and HA‐tagged Hsp70 (HA‐Hsp70). SODG85R‐GFP showed three distinct localization patterns: cytoplasmic, pre‐aggresomal and aggresomal (see representative pictures on the right and supplementary Fig S2F online). The percentages of cells bearing pre‐aggresomal (upper panel) and aggresomal (lower panel) SODG85R‐GFP are shown. Scale bar, 10 μm.",
    "ncbi_link": "BAG3: 9531
Hsp70: 3308
SOD: 6647"
  },
  {
    "caption": "(C) HEK cells transfected with SODG85R‐GFP, BAG3 and Hsp70 were additionally transfected with FLAG‐p50, as indicated. Diagrams show the percentages of cells with pre‐aggresomal and aggresomal SODG85R‐GFP. Right panel: representative image showing pre‐aggresomal localization of FLAG‐p50 and SODG85R‐GFP. Scale bar, 5 μm.",
    "ncbi_link": "p50: 51008
BAG3: 9531
Hsp70: 3308
SOD: 6647"
  },
  {
    "caption": "(D) GST pull‐down analysis as in (A), but in HEK cells transfected for 18 h with SODWT‐GFP or mutant SODG85R‐GFP, along with FLAG‐BAG3.",
    "ncbi_link": "SOD: 6647"
  },
  {
    "caption": "(E) HEK cells were transfected with the indicated plasmids with nonsense or bag3 siRNA. At 6 h after transfection, lactacystin (10 μM) or GST as vehicle control was added for GST and GST pull‐down analysis was performed as in (D).",
    "ncbi_link": "bag3: 9531"
  },
  {
    "caption": "(H) GST pull‐down analysis of SODG85R‐GFP as in (D) but in cells treated with PYR41 (10 μM; 12 h), as indicated. DIC, dynein intermediate chain; DMSO, dimethyl sulphoxide; GST, glutathione‐S‐transferase; HA, haemagglutinin; Hsp70, heat‐shock protein 70; NS, not significant; nons, nonsense; PxxP, proline‐rich repeat; siRNA, short‐interfering RNA; SOD, superoxide dismutase; SODWT, wild‐type SOD.",
    "ncbi_link": "SOD: 6647"
  },
  {
    "caption": "(A) Analysis of SODG85R‐GFP (green) localization with aggresome marker vimentin, the autophagic receptors p62 and NBR1, the autophagosome marker LC3 and the lysosomal marker LAMP2 (all in red) in BAG3/Hsp70‐transfected HEK cells. Representative merged images of cells with cytoplasmic, pre‐aggresomal and aggresomal SOD distribution are shown. Arrows indicate LC3‐positive autophagosomes. Scale bar, 5 μm.",
    "ncbi_link": "BAG3: 9531
Hsp70: 3308"
  },
  {
    "caption": "(E) Similar analysis as in (C) but in cells transfected 24 h before with nonsense or atg7 siRNA.",
    "ncbi_link": "atg7: 10533"
  },
  {
    "caption": "(F) HEK cells were transfected with SODG85R‐GFP and indicated FLAG‐tagged BAG3 constructs together with HA‐Hsp70, and lysosomal degradation of SODG85R‐GFP was examined as in (C). Corresponding immunoblots are shown in supplementary Fig S3F online. Ag, aggresome; BafA1, bafilomycin A1; GFP, green fluorescent protein; HA, haemagglutinin; Hsp70, heat‐shock protein 70; N, nucleus; NS, not significant; nons, nonsense; PxxP, proline‐rich repeat; siRNA, short interfering RNA; SOD, superoxide dismutase; SODWT, wild‐type SOD.",
    "ncbi_link": "SOD: 6647"
  },
  {
    "caption": "(A) Spinal cord sections of mice overexpressing SODWT and SODG85R (disease end‐stage) were immunostained for BAG3 and SOD1. Arrows indicate SOD1‐ and BAG3‐positive aggregates in the neuropil. Scale bar, 20 μm.",
    "ncbi_link": "SOD: 20655///20657
SOD: 20657///20655"
  },
  {
    "caption": "(A) Nissl-stained sagittal brain sections reveal no change in hippocampal morphology between Clcn3unc/unc and Clcn3+/+ mice at P45 or after 20 months. In contrast, the hippocampus was absent (indicated by asterisk) in 3 months-old Clcn3-/- mice (scale bar: 200 µm).",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(B) Nissl-stained paraffin sections show intact retinal layers in 20 months old Clcn3unc/un mice. Neurodegeneration in Clcn3-/- mice however, results in a loss of retinal structure already at 11 weeks of age (scale bar: 100 µm). RPE, retinal pigment epithelium; OS, photoreceptor outer segments; IS, photoreceptor inner segments; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(C) Immunoblots for ClC-3, -4 and -5 of membrane fractions of WT (+/+), Clcn3unc/unc (unc/unc), Clcn3unc/+ (unc/+) and Clcn3-/- (-/-) mice. β-actin, loading control.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(D) Representative Western blot for ClC-4 of membrane fractions from brain and kidney of WT (+/+), Clcn3+/- (+/-) and Clcn3-/- (-/-) mice. β-actin, loading control. (E) Quantification of ClC-4 immunoblots including those shown in (C and D) (normalized to actin). Mean values ± s.e.m. Average from ≥5 animals per genotype and at ≥2 immunoblots per animal. *** p < 0.0005 , ** p < 0.005, * p < 0.05 (two-tailed unpaired t test). ",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(A) Co-immunoprecipitation reveals a ClC-3-ClC-4 complex. 10% of solubilized brain membranes of WT and Clcn3unc/unc mice were directly loaded on the gel (input, or first immunoprecipitated (IP) with antibodies against ClC-3 or ClC-4. Western blots were probed for ClC-3 and ClC-4. Equivalent amounts of lysates and precipitates were loaded. * unspecific band / contamination.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(B) FRET experiments show homo- and heteromerization of ClC-3 and ClC-4 constructs (fused to yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP)) overexpressed in COS-7 cells. Co-expressed constructs are indicated. Graph represents energy transfer efficiencies from acceptor photobleaching, depicted as bleach corrected values (subtraction of ClC-4CFP alone). Mean values ± s.e.m. N = 20 (ClC-3YFP / ClC-4CFP); 33 (ClC-3YFP / ClC-3CFP); 26 (ClC-4YFP / ClC-4CFP); 42 (ClC-3YFP / Lamp-1CFP) cells. *** p < 0.0005 (two-tailed unpaired t test)",
    "ncbi_link": "CFP: 
cyan fluorescent protein: 
yellow fluorescent protein: 
YFP: "
  },
  {
    "caption": "(C) Immunolabelling shows subcellular localization of hClC-4 (top, green in merge), hClC-3 (middle, green in merge) and hClC-3unc (bottom, green in merge) of transiently transfected COS-7 cells, in comparison to either PDI or Lamp-1 (both red) as marker for the ER and late endosomes/lysosomes, respectively.",
    "ncbi_link": "hClC-3: 1182"
  },
  {
    "caption": "(D) Co-localization of hClC-3 and hClC-4 in cytoplasmic vesicles of COS-7 cells transfected with hClC-4 cDNA (hemagglutinin (HA) tagged) together with either hClC-3 or hClC-3unc. Immunostaining used antibodies against ClC-3 and HA tag (green and red in merge, respectively).",
    "ncbi_link": "HA: 
hemagglutinin: 
hClC-3: 1182
hClC-4: 1183"
  },
  {
    "caption": "(A) Clcn3unc/unc/Clcn4-/- and Clcn3-/- mice died within 3-4 weeks after birth. Approximately 20% of the animals survived in either line (Clcn3unc/unc/Clcn4-/-, n = 136 and Clcn3-/-, n = 187). All Clcn3-/-/Clcn4-/- mice (n= 4) died within 1-2 weeks after birth.",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(B) Nissl-stained paraffin sections show progressive neuronal cell loss (arrows) that begins in hippocampal CA1 region of P14 Clcn3unc/unc/Clcn4-/- mice and results in a complete loss of the hippocampus at P28. Neurodegeneration progresses slower in Clcn3-/- mice Stobrawa et al, 2001() (scale bar: 200 µm).",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(C) Semi-thin sections of P28 retinae revealed degeneration of photoreceptor cells in the outer nuclear layer and outer and inner segment of Clcn3unc/unc/Clcn4-/-, but not of Clcn3unc/unc or Clcn4-/- mice (scale bar: 50 µm). RPE, retinal pigment epithelium; OS, photoreceptor outer segments; IS, photoreceptor inner segments; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer.",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(A) GFP antibodies immunolabel VenusClC-3 (green) in the somata of CA1 pyramidal neurons of Clcn3ven/ven, but not Clcn3+/+ brain sections. sp, stratum pyramidale (scale bar: 20 µm).",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(B) Co-immunolabelling of VenusClC-3 (green) with ClC-4 (red) in the CA3 region of Clcn3ven/ven mice (scale bar: 20 µm). sl, stratum lucidum; sp, stratum pyramidale.",
    "ncbi_link": "ven: 
Clcn3: 12725"
  },
  {
    "caption": "(C) Co-immunostaining of VenusClC-3 (green) with EEA1 (red, left panel), Lamp-1 (red, middle panel) or synaptophysin (red, right panel) in either CA1 or CA3 region of Clcn3ven/ven mice. Arrows indicate structures of overlap (scale bar: 5 µm).",
    "ncbi_link": "ven: 
Clcn3: 12725"
  },
  {
    "caption": "(E) Immuno-blot analysis of fractions collected during preparation of SVs from brain of Clcn3ven/ven mice. VenusClC-3 (detected with GFP antibody) co-purified with SV marker protein synaptophysin.",
    "ncbi_link": "ven: 
Clcn3: 12725"
  },
  {
    "caption": "(A) Immunoblots for ClC-3, ClC-4, VGLUT1, VGLUT2, VGAT, GluR4 and GABAA-R-α1 of whole lysates from brain of Clcn3+/+ and Clcn3-/- mice at 2, 6 and 12 weeks of age.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(B) Acidification of synaptic vesicle LP2 fractions from Clcn3unc/unc and Clcn3+/+ mice at one year of age (upper panel, n= 2 animals each and ≥3 measurements per animal), 10-weeks-old Clcn4-/- and WT mice (middle panel, n= 3 animals each and ≥3 measurements per animal), and 4-6-weeks-old Clcn3unc/unc/Clcn4-/- and control mice (lower panel, 6 animals each with ≥2 measurements per animal). A decrease in fluorescence reflects acidification. The protonophore FCCP dissipated the pH gradient. Mean values ± s.e.m.",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(C) Quantification of ATP-induced acidification of LP2 fractions derived from 2, 6, and 10-12 weeks-old Clcn3-/- compared to wild-type mice. Acidification measured by acridine orange fluorescence in the presence of 60 mM KCl. At least 2 animals in at least 2 independent experiments were pooled. Each measurement was performed at least 3 times. Mean ± s.e.m. is shown.* p < 0.05, *** p < 0.0005 (two-tailed unpaired t test).",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "(D) Immunoblot revealed strong reduction of VGLUT1 levels in the homogenate (H) and LP2 fraction of Clcn3unc/unc/Clcn4-/- mice.",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(E) Endosomal pH of Clcn3+/+ and Clcn3-/- primary hippocampal neurons determined with a pH-sensitive transferrin conjugate. N= 5 independent cell lines with at least 2 live cell dishes per cell line with about 10 images each and ≥10 Tfn-positive compartments per image and genotype were analysed. Mean ± s.e.m. is shown.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "Miniature inhibitory postsynaptic currents (mIPSCs) measured in CA1 pyramidal neurons in different mouse models at P14-P16. (A) example mIPSCs of WT (left) and Clcn3-/- neurons.",
    "ncbi_link": "Clcn3: 12725"
  },
  {
    "caption": "Mean values ± s.e.m. and cumulative histogram of amplitude (top) and frequency/interevent-interval (bottom) of mIPSCs in different mouse-models as indicated . Several cells of 3 mice of each genotype were analyzed. Compared genotypes were siblings. No difference in amplitude or frequency/ interevent-interval distribution of mIPSCs was found in (B) Clcn3-/- and Clcn3+/+ (Clcn3+/+: 16 cells, Clcn3-/-: 15 cells; mean amplitude: p > 0.8, t test; mean frequency: p > 0.4, MW-test), in (C) Clcn3unc/unc and Clcn3+/+ (Clcn3+/+: 21 cells, Clcn3unc/unc: 13 cells; mean amplitude: p > 0.7; mean frequency: p = 0.3, t test), and in (D) Clcn4-/- and Clcn3+/+ (Clcn3+/+: 18 cells, Clcn4-/-: 18 cells; mean amplitude: p > 0.3, t-test; mean frequency: p = 0.6, MW-test).",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(E) No difference in mean amplitude (p > 0.5, t test), in cumulative amplitude and mean frequency of mIPSCs (p > 0.1, t test) was found in Clcn3unc/unc/Clcn4-/- and Clcn3+/+/Clcn4-/-. The interevent-interval distribution was shifted to the right, indicating a reduced frequency of mIPSCs in Clcn3unc/unc/Clcn4-/- (KS-test, p < 0,05) (Clcn3+/+/Clcn4-/-: 16 cells, Clcn3unc/unc/Clcn4-/-: 12 cells).",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(F,G) miniature excitatory postsynaptic currents (mEPSCs). (F) example traces of mEPSCs in WT and Clcn3-/- neurons (G) No significant difference between Clcn3unc/unc/Clcn4-/- and Clcn3+/+/Clcn4-/- mEPSCs in mean amplitudes (p > 0.9, t test) or in the distribution of amplitudes (Clcn4-/-: 12 cells, 2 mice; Clcn3unc/unc/Clcn4-/-: 8 cells, 2 mice).",
    "ncbi_link": "Clcn3: 12725
Clcn4: 12727"
  },
  {
    "caption": "(H) Primary hippocampal neurons co-transfected with ClC-3 and synaptobrevin (syb2), both luminally tagged with pHluorin or the pH-sensitive mOrange Ramirez et al, 2012(), respectively, were stimulated by 200 action potentials (APs) at 20 Hz (indicated by bar). Vesicle exocytosis was monitored by fluorescence increase upon exposure to extracellular neutral pH. Note that only Syb2 and not ClC-3 shows signs of exocytosis. Traces were corrected for photobleaching. The initial decay of the pHluorin signal is probably due to the high light exposure, which forces the fluorophores into a transient dark-state Dean et al, 2011(). Averaged fluorescence traces (n=10), error bars, s.e.m.",
    "ncbi_link": "mOrange: 
pHluorin: 
ClC-3: 1182
syb2: 24803
synaptobrevin: 24803"
  },
  {
    "caption": "C. Boxplots showing the mean mRNA expression of ENAH gene (hMENA) for 22 patients in the 10 groups of cell types (Peng et al., 2019) (total number of cells: 38487, mean of cells for patient: 1603). Shown in each boxplot are the median value (horizontal line), 25th-75th percentiles (box outline), and highest and lowest values within 1.5x of the inter-quartile range (vertical line). Expressions from each cell-type group were compared to all other groups by using Mann-Whitney U-test (two-sided) and P-values were adjusted for multiple testing using the Benjamini-Hochberg method. Stromal cell-type groups with significantly up-regulated ENAH expression respect to other stromal groups are: Fibroblast, ***q=0.0002; Stellate, ***q= 1.5e-07. Non-stromal cell-type groups with significantly up-regulated ENAH expression with respect to other non-stromal groups are: Ductal 1, **q=0.0013.",
    "ncbi_link": "ENAH: 55740
hMENA: 55740"
  },
  {
    "caption": "D. Boxplots showing the mRNA expression of ENAH gene (hMENA) in the 7 groups of cell types from (Lambrechts et al., 2018) (total n=52). Shown in each boxplot are the median value (horizontal line), 25th-75th percentiles (box outline), and highest and lowest values within 1.5x of the inter-quartile range (vertical line). Cell expression from each group were compared to all other stromal/not-stromal cells by using Mann-Whitney U-test (two-sided) and P-values were adjusted for multiple testing using the Benjamini-Hochberg method (Fibroblast group vs other stromal groups, **q=0.0022; Other comparisons, q>0.05",
    "ncbi_link": "ENAH: 55740
hMENA: 55740"
  },
  {
    "caption": "A. Quantification of in vitro matrigel invasion assay (bottom) of P-CAF and L-CAF (P-CAF # 36, 138 and L-CAF #189, 484) transfected with control siRNA (CNT) or hMENA siRNA (hMENA(t)) indicating that the siRNA‐mediated knock‐down of hMENA/hMENA∆v6 reduces the invasive ability of CAFs with respect to siCNT CAFs. Number of invading cells was measured by counting 6 random fields. Data are presented as the mean ± SD of two biological replicates, performed in triplicates each. Immunoblot showing hMENA/hMENAΔv6 expression (detected by Pan-hMENA mAb and by the specific anti-hMENAΔv6 antibody) of the CAFs employed is reported (top). TUBULIN was used as loading control. P values were calculated by two‐sided Student's t‐test. *P<0.05, ***P<0.001.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "B. Quantification of in vitro matrigel invasion assay (bottom) of P-NF and L-NF and P-CAF#110 and L-CAF#400 transfected with control or hMENA∆v6 expressing vectors, demonstrating that the overexpression of hMENA∆v6 isoform induced the invasiveness of P-NFs and L-NFs and/or P-and L-CAFs. Number of invading cells was measured by counting 6 random fields. Data are presented as the mean ± SD of two biological replicates, performed in triplicates each. Immunoblot of hMENAΔv6 expression (detected by the specific anti-hMENAΔv6 antibody) in fibroblasts employed is reported (top). TUBULIN was used as loading control. P values were calculated by two‐sided Student's t‐test. *P<0.05, ***P<0.001.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "B. Quantification of in vitro matrigel invasion assay of PANC-1 cultured for 48 h with CM derived from control P-CAFs#36 (siCNT-P-CAF-CM#36) and hMENA/hMENA∆v6 silenced P-CAFs (sihMENA(t)-P-CAF-CM#36), showing that the siRNA‐mediated knock‐down of hMENA/hMENA∆v6 affects PANC-1 invasive ability mediated by CAF-CM. Culture medium (DMEM) was used as control. Cells invading matrigel were counted in 6 random fields. Data are presented as the mean ± SD of three biological replicates. Statistical analysis was performed with one-way ANOVA P=0.006, followed by Bonferroni's multiple comparison test. *P < 0.05, **P<0.01.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "D. Quantification of in vitro matrigel invasion assay of H1975 cultured for 48 h with CM derived from control L-CAFs#484 (siCNT-L-CAF-CM#484) and hMENA/hMENA∆v6 silenced L-CAFs (sihMENA(t)-L-CAF-CM#484), showing that the siRNA‐mediated knock‐down of hMENA/hMENA∆v6 affects H1975 invasive ability mediated by CAF-CM. Culture medium (DMEM) was used as control. Cells invading matrigel were counted in 6 random fields. Data are presented as the mean ± SD of six replicates. Statistical analysis was performed with one-way ANOVA P=0.006, followed by Bonferroni's multiple comparison test. *P < 0.05, **P<0.01.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "F. Representative images (top) and quantification (bottom) of collagen gel-contraction ability of CAFs (monoculture) or CAFs co-cultured with siCNT (co-siCNT) or sihMENA(t) PANC-1 cells (co-sihMENA(t)). Dashed white circles illustrate the margins of the gel area. Data are presented as the mean ± SD of two biological replicates. Statistical analysis was performed with one-way ANOVA P=0.005, followed by Bonferroni's multiple comparison test ANOVA: *P<0.05, **P<0.01.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "G. Representative immunoblot (top) and quantification (bottom) of hMENA∆v6 and α-SMA expression in P-CAFs #110 treated with DMEM medium (-) or with conditioned medium (CM) derived from siCNT (siCNT PANC-1) or sihMENA(t) PANC-1 cells ((sihMENA(t) PANC-1) (n = 3). Data are represented as fold increase with respect to DMEM (set as 1± SD). Data presented were analyzed using two‐sided Student's t‐test: *P<0.05.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "C. Real time qRT-PCR analysis of the relative GAS6 mRNA expression level in NFs (P-NF#1), P-CAF low and P-CAF high, as described above. Data are presented as the mean ± SD of three replicates. Statistical analysis was performed with one-way ANOVA P=0.001, followed by Bonferroni's multiple comparison test. *P< 0.05, **P<0.01.",
    "ncbi_link": "GAS6: 2621"
  },
  {
    "caption": "D. Real time qRT-PCR analysis of the relative GAS6 mRNA expression level in PANC-1 and P-CAF (n=3), showing a low GAS6 expression in PANC-1 cells. Data are presented as the mean ± SD. P values were calculated by two‐sided Student's t‐test. ***P<0.001.",
    "ncbi_link": "GAS6: 2621"
  },
  {
    "caption": "E. Boxplots showing the mRNA expression of GAS6 in normal lung fibroblasts (white) (n=15) versus primary NSCLC fibroblasts (light blue) (n=15) (GSE22862 data set). In each boxplot the median value (horizontal line), 25th-75th percentiles (box outline), and highest and lowest values within 1.5x of the inter-quartile range (vertical line) are shown. Statistical significance was calculated by Mann-Whitney U-test (two-sided) (P=0.0208).",
    "ncbi_link": "GAS6: 2621"
  },
  {
    "caption": "F, G. Real time qRT-PCR analysis of P#138 CAF (F) and L#189 CAF (G) transfected with control siRNA (siCNT) or hMENA(t) siRNA (sihMENA(t)) as representative cases. The siRNA‐mediated knock‐down of hMENA/hMENA∆v6 resulted in a significant reduction of GAS6 mRNA expression levels compared to siCNT cells (set as 100). Data are presented as the mean ± SD of three replicates. P values were calculated by two‐sided Student's t‐test **P<0.01, ***P<0.001.",
    "ncbi_link": "hMENA: 55740
GAS6: 2621"
  },
  {
    "caption": "H. Quantification of matrigel invasion assay of PANC-1 cultured for 48 h with DMEM (culture medium), or conditioned medium (CM) derived from control siRNA P#106 CAFs (siCNT P-CAF-CM), GAS6 siRNA (siGAS6 P-CAF-CM), hMENA(t) siRNA (sihMENA(t) P-CAF-CM), hMENA(t) siRNA plus rGAS6 (sihMENA(t) P-CAF-CM +rGAS6). Number of invaded PANC-1 cells after 48 h of treatment was measured by counting 6 random fields. Data are presented as the mean ± SD of three biological replicates. Statistical analysis was performed with one-way ANOVA P=0.004, followed by Bonferroni's multiple comparison test. *P< 0.05, **P<0.01.",
    "ncbi_link": "hMENA: 55740
GAS6: 2621"
  },
  {
    "caption": "A. Immunoblot of AXL expression in PANC-1 and A549 cancer cells upon transfection of control siRNA (CNT) or hMENA(t) siRNA (sihMENA(t)), indicating that the knock‐down of hMENA isoforms, resulted in a reduction of AXL protein expression.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "B. Real time qRT-PCR analysis of the relative AXL mRNA expression in PANC-1 and A549 cancer cells transfected with control siRNA (siCNT) or hMENA(t) siRNA (sihMENA(t)), indicating that the knock‐down of hMENA isoforms, resulted in a significant reduction of mRNA AXL expression. Data are presented as the mean ± SD of three replicates. P values were calculated by two‐sided Student's t‐test. **P<0.01, ***P<0.001.",
    "ncbi_link": "AXL: 558
hMENA: 55740"
  },
  {
    "caption": "C. Real time qRT-PCR analysis of the relative levels of mature AXL mRNA or AXL pre-mRNA in PANC-1 (left) and A549 (right) cell lines, transfected with control siRNA (siCNT) or hMENA(t) siRNA, sihMENA(t). Data represent percent of AXL mRNA or pre-mRNA levels in hMENA(t) silenced cells relative to siCNT control cells (set at 100). Data are presented as the mean ± SD of two biological replicates. P values were calculated by two‐sided Student's t‐test. *P< 0.05, ***P<0.001.",
    "ncbi_link": "AXL: 558
hMENA: 55740"
  },
  {
    "caption": "D. Immunoblot analysis with the indicated antibodies of PANC-1 cells transfected with control siRNA (CNT) or hMENA(t) siRNA, showing that the knock‐down of total hMENA isoforms, (hMENA(t)) inhibits GAS6-mediated pAXL and pAKT expression. Cells were serum starved overnight and subsequently stimulated with DMSO (0.02%) in control culture medium (-) or rGAS6 (200 ng/mL), for 30 and 60 min. The fold change of pAXL or pAKT expression respect to siCNT untreated cells is reported.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "E. Quantification of in vitro matrigel invasion assay of PANC-1 siCNT cells (siCNT) and hMENA/hMENA∆v6 silenced cells (sihMENA(t)) toward rGAS6 as chemo-attractant (siCNT + rGAS6 and sihMENA(t) + rGAS6), showing that the knock‐down of hMENA(t) reduced cancer cell invasion toward GAS6. The number of invading cells were counted in 6 random fields. Data are presented as the mean ± SD of three biological replicates. Statistical analysis was performed with one-way ANOVA P<0.0001, followed by Bonferroni's multiple comparison test. **P<0.01.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "F. Quantification of in vitro matrigel invasion assay of PANC-1 siCNT cells (siCNT) and hMENA/hMENA∆v6 silenced cells (sihMENA(t)), untreated (-) or treated with conditioned media derived from CAFs (P-CAF#36-CM) for 48 h. The number of invaded cells were counted in 6 random fields. Data are presented as the mean ± SD of three biological replicates. Statistical analysis was performed with one-way ANOVA P<0.0001, followed by Bonferroni's multiple comparison test. *** P< 0.001.",
    "ncbi_link": "hMENA: 55740"
  },
  {
    "caption": "A. Overall survival (OS) curves in Pancreatic Adenocarcinoma patients (PDAC) (n=172) from The Cancer Genome Atlas (TCGA), showed that combined expression of AXL, GAS6 and ENAH (hMENA), is a prognostic signature in PDAC.",
    "ncbi_link": "AXL: 558
ENAH: 55740
hMENA: 55740
GAS6: 2621"
  },
  {
    "caption": "B. Overall survival (OS) curves in Lung Squamous cancer patients (LUSC) (n=501) from The Cancer Genome Atlas (TCGA), showed that combined expression of AXL, GAS6 and ENAH (hMENA), is a prognostic signature in LUSC.",
    "ncbi_link": "AXL: 558
ENAH: 55740
hMENA: 55740
GAS6: 2621"
  },
  {
    "caption": "Size exclusion chromatography (SEC) results for MICU2_WT and a set of mutants in the presence of Ca2+ monitored at 280 nm absorption wavelength. Size exclusion chromatography (SEC) results for MICU2_WT and a set of mutants in the presence of EGTA monitored at 280 nm absorption wavelength.",
    "ncbi_link": "MICU2: 221154"
  },
  {
    "caption": "MICU2_WT (A), MICU2_K172A (B) were pulled-down by GST-MICU1 both in the absence and presence of 2 mM Ca2+. MICU2_EF1mut was not pulled-down by GST-MICU1 in the presence of 2 mM Ca2+ (C), while MICU2_EF2mut was pulled-down by GST-MICU1 both in the absence and presence of 2 mM Ca2+ (D). MICU2_R352A was not pulled-down by GST-MICU1 in the absence of 2 mM Ca2+ (E), while MICU2_E329A was pulled-down by GST-MICU1 both in the absence and presence of 2 mM Ca2+ (F). MICU2_D185A was partially pulled-down by GST-MICU1 in the presence of Ca2+, while they showed a strong interaction in the absence of 2 mM Ca2+. MICU2_E196K was not pulled-down by GST-MICU1 in the presence of 2 mM Ca2+, while a strong interaction was observed in the absence of 2 mM Ca2+.",
    "ncbi_link": "MICU2: 221154"
  },
  {
    "caption": "CRH-Cre::Ai9 reporter male mice fed on chow or 4 weeks on HFD were used to examine c-Fos expression in the PVH in 24hr fasting or refed after 24hr fasting. A) Representative images showing CRH neurons (red in the first colomn), c-Fos expression (green in the second colomn), merged of red and green (the third colomn) and the amplied pictures for the boxed areas in the merged images (the forth colomn). The experimental conditions for each group (fasting verus refed, chow versus HFD) are labelled on the left. Scale bar=200µm.",
    "ncbi_link": "Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "CRH-Cre mice received delivery of AAV-Flex-GCaMP6m viral vectors to bilateral PVH and optic fiber implantation targeting PVH neurons, and were used for in vivo live recording. (H-I) Representative traces showing recordings of activity changes in CRH neuron in response to stressor (water spray) in chow-fed controls (H), and 4 weeks after HFD (I), (J) Comparison of average responses in the two conditions, n=4 each, **p=0.0006, paired Student's t test.",
    "ncbi_link": "GCaMP6m: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-Flex-EGFP-P2A-mNachBac vectors at 7-8 weeks of age and recordings were made at least 4 weeks after viral delivery on neurons with NachBac (one side) or control neurons (contralateral side) of the same animal (A);",
    "ncbi_link": "EF1a: 
EGFP: 
mNachBac: 
P2A: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "typical action potentials (APs) in controls (B, top panel) and typical NachBac-mediated APs showing lower threshold and long duration (B, bottom, the inset highlighting the long duration) in NachBac mice",
    "ncbi_link": "NachBac: "
  },
  {
    "caption": "CRH-Cre male mice were injected with either AAV-Flex-GFP or AAV-EF1a-Flex-EGFP-P2A-mNachBac to examine c-Fos expression in the PVH in 24hr fasting or refed after fasting. (D) Representative images showing CRH neurons expressing GFP or NachBac (GFP in the top 2 rows and NachBac in the bottom 2 rows of the first colomn), c-Fos expression (red in the second colomn), merged of red and green (the third colomn) and the amplied pictures for the boxed areas in the merged images (the forth colomn). The experimental conditions for each group (fasting verus refed) are labelled on the left.",
    "ncbi_link": "EF1a: 
EGFP: 
GFP: 
mNachBac: 
P2A: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "(E-F) Comparison of average neuron numbers from cell counting on total number of c-Fos positive neurons in the PVH (E, **p<0.0001: fasting versus refed; **p=0.0026: fasting versus fasting/NachBac; **p<0.0001: fasting/NachBac versus refed/NachBac) and total number of c-Fos positive CRH neurons (F, **p<0.0001: fasting versus refed; **p<0.0001: fasting versus fasting/NachBac; p=0.3423: fasting/NachBac versus refed/NachBac), n=3-4 each, data presented as mean +/- SEM, two way ANOVA tests.",
    "ncbi_link": "NachBac: "
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of a mixture of AAV-Flex-GCaMP6m and AAV-EF1a-Flex-EGFP-P2A-mNachBac vectors at 7-8 weeks of age with optic fiber implantation targeting PVH neurons. (G-H) Representative traces showing typical responses of PVH CRH neurons to water spay (arrows) in NachBac mice (G), and comparison of responsiveness to water spray between NachBac and control mice (H).",
    "ncbi_link": "EF1a: 
EGFP: 
GCaMP6m: 
mNachBac: 
NachBac: 
P2A: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "(I-J) Representative traces showing typical responses of PVH CRH neurons to water spay (arrows) in NachBac mice (I), and comparison of responsiveness to water spray between NachBac and control mice (J).Gray traces showed Ca2+ independent signal for system stability and red ones showed Ca2+ dependent signals for neuron activity, N=5-7 each, males, data presented as mean +/-SEM, **p<0.0001 in both (H and J), unpaired Student's t tests.",
    "ncbi_link": "NachBac: "
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-Flex-EGFP-P2A-mNachBac or control GFP vectors at 7-8 weeks of age and were maintained on chow diet for 7 weeks before switching to HFD. Weekly body weight gain after viral delivery (A) at 11 weeks after viral delivery.",
    "ncbi_link": "EF1a: 
EGFP: 
GFP: 
mNachBac: 
P2A: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-Flex-EGFP-P2A-mNachBac or control GFP vectors at 7-8 weeks of age and were maintained on chow diet for 7 weeks before switching to HFD. measurements of fat mass (B) and lean mass (C) at 11 weeks after viral delivery.",
    "ncbi_link": "EF1a: 
EGFP: 
GFP: 
mNachBac: 
P2A: 
Cre: 2777477
CRH: 12918"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-DIO-Kir2.1-P2A-dTomato vectors and AAV-Flex-GFP at 7-8 weeks of age and recording was made at least 4 weeks after viral delivery on neurons with Kir2.1 (one side) or control GFP neurons (contralateral side) of the same animal (A)",
    "ncbi_link": "dTomato: 
EF1a: 
GFP: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "typical spontaneous neuron activity recorded in GFP controls (B, top panel) and Kir2.1 neurons (B, bottom); and comparison in resting membrane potentials between the two groups (C, **p<0.0001, unpaired Student's t test).",
    "ncbi_link": "Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice were injected with either AAV-Flex-mCherry or AAV-EF1a-DIO-Kir2.1-P2A-dTomato to examine c-Fos expression in the PVH in 24hr fasting or refed after fasting. (D) Representative images showing CRH neurons expressing mCherry or Kir2.1 (mCherry in the top 2 rows and Kir2.1 in the bottom 2 rows of the second colomn), c-Fos expression (green in the first colomn), merged of red and green (the third colomn) and the amplied pictures for the boxed areas in the merged images (the forth colomn). The experimental conditions for each group (fasting verus refed) are labelled on the left.",
    "ncbi_link": "dTomato: 
EF1a: 
mCherry: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice were injected with either AAV-Flex-mCherry or AAV-EF1a-DIO-Kir2.1-P2A-dTomato to examine c-Fos expression in the PVH in 24hr fasting or refed after fasting. (E-F) Comparison of average neuron numbers from cell counting on total number of c-Fos positive neurons in the PVH (E, **p=0.0001: fasting versus refed; *p=0.0497: refed versus refed/Kir2.1; **p=0.0025: fasting/Kir2.1 versus refed Kir2.1) and total number of c-Fos positive CRH neurons (F, **p<0.0001: fasting versus refed; p=0.9586: fasting/Kir2.1 versus refed/Kir2.1), n=3-4 each, two way ANOVA tests. All data presented as mean +/- SEM.",
    "ncbi_link": "dTomato: 
EF1a: 
mCherry: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of a mixture of AAV-Flex-GCaMP6m and AAV-EF1a-DIO-Kir2.1-P2A-dTomato vectors at 7-8 weeks of age with optic fiber implantation targeting PVH neurons. (G-H) Representative traces showing typical responses of PVH CRH neurons to water spay (arrows) in Kir2.1 mice (G), and comparison of responsiveness to water spray between Kir2.1 and control mice (H).",
    "ncbi_link": "dTomato: 
EF1a: 
GCaMP6m: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of a mixture of AAV-Flex-GCaMP6m and AAV-EF1a-DIO-Kir2.1-P2A-dTomato vectors at 7-8 weeks of age with optic fiber implantation targeting PVH neurons.",
    "ncbi_link": "dTomato: 
EF1a: 
GCaMP6m: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-DIO-Kir2.1-P2A-dTomato or control AAV-Flex-mCherry vectors at 7-8 weeks of age and were maintained on chow diet for 7 weeks before switching to HFD. Weekly body weight gain after viral delivery (A, *p<0.0001, unpaired Student's t test), at 15 weeks after viral delivery.",
    "ncbi_link": "dTomato: 
EF1a: 
mCherry: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "CRH-Cre male mice received stereotaxic delivery of AAV-EF1a-DIO-Kir2.1-P2A-dTomato or control AAV-Flex-mCherry vectors at 7-8 weeks of age and were maintained on chow diet for 7 weeks before switching to HFD. measurements of fat mass (B, **p=0.0006, unpaired Student's t test) and lean mass (C, p=0.3728, unpaired Student's t test) at 15 weeks after viral delivery.",
    "ncbi_link": "dTomato: 
EF1a: 
mCherry: 
P2A: 
Cre: 2777477
CRH: 12918
Kir2.1: 16518"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in the colon of DSS-challenged and control mice (n=6 per group).",
    "ncbi_link": "Lif: 16878"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in LPLs and IECs from DSS-challenged and control mice (n=4 per group).",
    "ncbi_link": "Lif: 16878"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in the colon of SPF mice treated with or without antibiotics (Abx) at the indicated time points during colitis induction (n=3 per group).",
    "ncbi_link": "Lif: 16878"
  },
  {
    "caption": "Quantitative expression of Lif mRNA in LPLs and IECs from mice treated with or without Abx at the indicated time points during colitis induction (n=3 per group).",
    "ncbi_link": "Lif: 16878"
  },
  {
    "caption": "Stat4 mRNA expression in LPLs and IECs (n=6).",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Weight loss of wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. Macroscopic changes in the colon of the mice on day 10 of colitis induction Comparison of the colon length in the mice on day 10 of colitis induction",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. DAI (stool consistency and bleeding score) of colitis mice treated",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "wild-type (WT) (n=6) or Stat4 knockout(Stat4-KO) (n=6) mice receiving intraperitoneal injection of PBS or LIF during challenge with 3% DSS. H&E histology of representative colons from colitis mice. Scale bar, 20μm.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Weight loss of Rag1-/- (n=6) mice transferred with CD45RBhi CD4+ T cells and intraperitoneally injected with PBS or LIF for 8 weeks.",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "Rag1-/- (n=6) mice transferred with CD45RBhi CD4+ T cells and intraperitoneally injected with PBS or LIF for 8 weeks. Macroscopic changes in the colon of Rag1-/- mice treated Comparison of colon lengths in the Rag1-/- mice at week 8 (n=5).",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "Rag1-/- (n=6) mice transferred with CD45RBhi CD4+ T cells and intraperitoneally injected with PBS or LIF for 8 weeks. H&E histology of representative mouse colons on day 54 of colitis induction",
    "ncbi_link": "Rag1: 19373"
  },
  {
    "caption": "Colons obtained from WT or Stat4-KO mice on day10 of the colitis model induced as in Figure 2A were immunostained with an antibody against phosphorylated STAT4. Scale bar, 50μm.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "FACS staining of LPLs isolated on day10 from the colon of WT or Stat4-KO colitis mice receiving PBS or LIF (n=4 per group). The percentage of IL-17A+ and/or IFNγ+ CD4+ T cells in vivo was analyzed.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Quantitative expression of Il17a mRNA in MLNs and LNs from colitis mice treated",
    "ncbi_link": "Il17a: 16171"
  },
  {
    "caption": "FACS staining of WT and Stat4-KO naïve CD4+ T cells treated with LIF (50 ng/ml) on day 4 of induction into Th17 cell subsets.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "qPCR analysis of Th17-related genes in WT or Stat4-KO naïve CD4+ T cells on day 4 of induction into Th17 cell subsets in the absence or presence of LIF (n=3 per group).",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "FACS staining of WT or Stat4-KO naïve CD4+ T cells treated with LIF (50 ng/ml) on day 4 of induction into nonpathogenic or pathogenic Th17 cells.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Cultured HeLa cells transfected with GFP-tagged STAT constructs were exposed to LIF and imaged 30 minutes later. Scale bar, 50μm.",
    "ncbi_link": "GFP: 
STAT: 20848"
  },
  {
    "caption": "Heatmap showing Th17 signature genes (left) or Th17 regulatory genes (right) up- or downregulated in WT or Stat4-KO LPLs by LIF treatment (n=2).",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Quantitative mRNA expression analysis of the indicated genes in WT or Stat4-KO naïve CD4+ T cells on day 4 of induction into Th17 cell subsets in the absence or presence of LIF.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "The GAS-luciferase reporter activity assay was performed in Stat3-/- MEFs transfected with empty vector (EV) or STAT4 constructs and then treated with LIF for 8 hours.",
    "ncbi_link": "Stat3: 20848
STAT4: 20849"
  },
  {
    "caption": "The GAS-luciferase reporter activity assay was performed in Stat3-/- MEFs transfected with empty vector (EV) or STAT4 constructs and then treated with LIF for 8 hours.",
    "ncbi_link": "Stat3: 20848
STAT4: 20849"
  },
  {
    "caption": "Relative SIE-(I) activities in Stat3-/- MEFs transfected with EV or the indicated STAT constructs and treated with LIF for 8 hours.",
    "ncbi_link": "STAT: 20848
Stat3: 20848"
  },
  {
    "caption": "Relative AGG-luciferase reporter activities in Stat3-/- MEFs transfected with EV or the indicated STAT constructs and treated with LIF for 8 hours.",
    "ncbi_link": "STAT: 20848
Stat3: 20848"
  },
  {
    "caption": "ChIP analysis of naïve CD4+ T cells obtained from IL-17A-eGFP mice cultured under Th0 or Th17 conditions in the absence or presence of LIF for 3 days. GFP+ cells isolated by flow cytometry were restimulated with IL-6 in the presence or absence of LIF, crosslinked with formaldehyde and immunoprecipitated with anti-STAT3 (top) or anti-STAT4 (bottom) antibodies, followed by the amplification of the immunoprecipitated DNA by quantitative PCR with the p1-p10 primer pairs. The results are presented relative to the amount of input DNA.",
    "ncbi_link": "eGFP: 
IL-17A: 16171"
  },
  {
    "caption": "ChIP analysis of naïve WT or Stat4-KO CD4+ T cells cultured under Th0 or Th17 conditions in the absence or presence of LIF for 3 days. The cells were restimulated with IL-6 or LIF for 30 minutes, crosslinked with formaldehyde and immunoprecipitated with the anti-STAT3 antibody, followed by the amplification of the immunoprecipitated DNA by quantitative PCR with the p1-p10 primer pairs. The results are presented relative to the amount of input DNA.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Relative Il17a-SIE- (left) or AGG-luciferase reporter (right) activities in Stat3-/- MEFs transfected with EV, STAT3 or STAT4 or cotransfected with STAT3 and STAT4 and then treated with IL-6 or LIF for 8 hours.",
    "ncbi_link": "Il17a: 16171
Stat3: 20848
STAT3: 20848
STAT4: 20849"
  },
  {
    "caption": "Relative Il17a promoter-luciferase reporter activities in Stat3-/- MEFs transfected with the indicated constructs and then treated with LIF for 8 hours.",
    "ncbi_link": "Il17a: 16171
Stat3: 20848"
  },
  {
    "caption": "Quantitative mRNA expression analysis of the indicated genes in colon tissues obtained from WT or Stat4-KO colitis mice treated",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Immunoblot analysis of YAP expression in WT or Stat4-KO IECs treated with LIF (20 ng/ml) for different durations; β-actin was used as a loading control (top). The statistical analysis of YAP protein intensity is shown in the bottom panel.",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "Relative YAP promoter-luciferase reporter activities in HEK293T cells transfected with EV, STAT3 or STAT4 and then treated with IL-6 or LIF for 8 hours.",
    "ncbi_link": "STAT3: 20848
STAT4: 20849
YAP: 10413"
  },
  {
    "caption": "16S rRNA sequencing analyses of the Proteobacteria distribution in feces from WT or Stat4-KO colitis mice. (n=5 per group).",
    "ncbi_link": "Stat4: 20849"
  },
  {
    "caption": "qPCR of the 16S rRNA genes of microbes in the phylum Proteobacteria, family Enterobacteriaceae, and genera Escherichia-Shigella in the feces of the indicated mice on day0 and day10 (n=6 per group) of colitis induction.",
    "ncbi_link": "16S rRNA: "
  },
  {
    "caption": "B. Semi-quantitative PCR of miR-132 and negative control miRNAs in the hippocampus of antagomiR-132-injected mice (ant-132) in comparison to control-injected animals (aCSF and scramble) at six months of age. Sample size, n=9 per group.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "C. FISH of miR-132 and negative control miR-124 in the hippocampus of ant-132- and scramble-injected mice. Scramble probes were used as FISH negative controls. Scale bar, 500μm.",
    "ncbi_link": "miR-124: 70441///268755///12797995
miR-132: 387150"
  },
  {
    "caption": "D. Semi-quantitative PCR of miR-132 and miR-212 in the hippocampus of 3-month old miR-132 mimic-injected mice (miR-132) compared to animals injected with a negative control oligonucleotide (Ctr). Sample size, n=6 per group.",
    "ncbi_link": "miR-132: 387150
miR-212: 387208"
  },
  {
    "caption": "A. Amyloid staining (6E10) combined with miR-132FISH in ant-132- and scramble-injected mice at six months of age. Scale bar, 500 μm. B. Quantification of amyloid burden in hippocampus and cortex of ant-132-injected and control animals (see Materials and Methods). Sample size, n=4 per group.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "C, D. ELISA of soluble (TBS) and insoluble (Formic acid) Aβ40 and Aβ42 levels in the hippocampus of ant-132- (C) and miR-132-injected (D) animals at six and three months of age, respectively. Sample size, n=6 per group.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Western blot analysis of total TAU and pTAU (AT8, AT270) levels upon miR-132 knockdown (A) or overexpression (B) at six and three months of age, respectively. Sample size, n=9 per group (A) and n=6 per group (B). Values were normalized to the respective control groups and presented as mean ± SEM. Student's t-test was used.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "A. Luciferasereporter assay of wild-type (wt) and mutant (mut) ITPKB 3'UTR in HEK293 cells co-transfected with a synthetic miR-132 (miR-132) or a negative control (Neg Ctr) oligonucleotide.",
    "ncbi_link": "Luciferase: 
ITPKB: 3707
miR-132: 406921"
  },
  {
    "caption": "B. ELISA of Aβ40 and Aβ42 levels in HEK293-APPswecells transfected with a miR-132 antisense oligonucleotide (miR-132 inh), an siRNA against ITPKB (ITPKB siRNA) or both. The assays in A and B were performed in three independent experiments, each in triplicates.",
    "ncbi_link": "APP: 351
ITPKB: 3707
miR-132: 406921"
  },
  {
    "caption": "C. Western blot analysis of ITPKB knock down in APPPS1hippocampus using an siRNA oligonucleotide against ITPKB. Sample size, n=6 per group. Values were normalized to control-injected group (Ctr) and presented as mean ± SEM.",
    "ncbi_link": "APP: 351
ITPKB: 320404
PS1: 5663"
  },
  {
    "caption": "D. ELISA of insoluble (Formic acid-soluble) Aβ40 and Aβ42 levels in the hippocampus of ITPKB siRNA- and control-injected animals at three months of age. Sample size, n=6 per group. Values were normalized to control group and presented as mean ± SEM.",
    "ncbi_link": "ITPKB: 320404"
  },
  {
    "caption": "E, F. Western blot analysis of ITPKB levels upon miR-132 down- (E) or up-regulation (F) at six and three months of age, respectively. Sample size, n=9 per group for miR-132 down regulation and n=6 per group for miR-132 overexpression. Values were normalized to control groups and presented as mean ± SEM.",
    "ncbi_link": "miR-132: 387150"
  },
  {
    "caption": "Western blot analysis of CTFβ (A) levels upon miR-132 down- (ant-132) (left panel) or upregulation (miR-132) (right panel) in APPPS1hippocampus at six and three months of age, respectively. Sample size, n=9 per group for miR-132 down regulation and n=6 per group for miR-132 overexpression. Values were normalized to respective control groups and presented as mean ± SEM. The Student's t-test was used.",
    "ncbi_link": "APP: 351
miR-132: 387150
PS1: 5663"
  },
  {
    "caption": "Western blot analysis of sAPPβ-swe (B) levels upon miR-132 down- (ant-132) (left panel) or upregulation (miR-132) (right panel) in APPPS1hippocampus at six and three months of age, respectively. Sample size, n=9 per group for miR-132 down regulation and n=6 per group for miR-132 overexpression. Values were normalized to respective control groups and presented as mean ± SEM. The Student's t-test was used.",
    "ncbi_link": "APP: 351
miR-132: 387150
PS1: 5663"
  },
  {
    "caption": "Western blot analysis of phosphorylated ERK1/2 (pERK1/2) (C) levels upon miR-132 down- (ant-132) (left panel) or upregulation (miR-132) (right panel) in APPPS1hippocampus at six and three months of age, respectively. Sample size, n=9 per group for miR-132 down regulation and n=6 per group for miR-132 overexpression. Values were normalized to respective control groups and presented as mean ± SEM. The Student's t-test was used.",
    "ncbi_link": "APP: 351
miR-132: 387150
PS1: 5663"
  },
  {
    "caption": "B. miR-132FISH coupled with double immunofluorescence against hyperphosphorylated TAU (AT8)-containing neurofibrillary tangles (NFTs) and ITPKB in AD prefrontal cortex. miR-124 was used as a control. Scale bar, 50 μm.",
    "ncbi_link": "miR-124: 406907///406909///406908
miR-132: 406921"
  },
  {
    "caption": "C. Quantification of miR-132, ITPKB and hyperphosphorylated TAU (pTAU) signal in single neurons. Integrated intensity values of each signal per cell were normalized to the mean integrated density of each signal across all the cells analyzed (see Materials and Methods). Sample size (AD patients), n=3. Values are presented as mean ± SEM. Two-way Anova was used. Quantifications are summarized in the table provided. Arrow directions refer to the comparison of each normalized signal to the same signal in the other group (in the \"low miR-132\" group comparisons are made to the \"high miR-132\" group and vice versa).",
    "ncbi_link": "miR-132: 406921"
  },
  {
    "caption": "Semi-quantitative PCR of miR-132 and western blot analysis of ITPKB, phosphorylated (pERK1/2) and total ERK1/2, phosphorylated (AT8 , AT270) and total TAU, phosphorylated sphingosine kinase 1 (pSphK1), BACE1, full length APP (flAPP), APP CTFs and sAPPβ in human AD hippocampi (AD) compared to non demented control samples (ND). Sample size, n=39 for AD and n=15 for ND. Values were normalized to ND and presented as mean ± SEM. The Student's t-test was used.",
    "ncbi_link": "ERK1: 
miR-132: 406921"
  },
  {
    "caption": "GAG content as assessed by Alcian blue staining with spectrophotometric B C28/I2 micromasses treated with GCP-2 siRNA (n=12) or scrambled control siRNA (Scr; n=14); p values were determined by unpaired two-tailed Student's t test.",
    "ncbi_link": "GCP-2: 10844"
  },
  {
    "caption": "D qPCR for ACAN (Aggrecan) expression in C3H10T½ micromasses treated for 3 days with recombinant GCP-2 (100 ng/ml) (n=3) or vehicle (n=4); ACAN - Aggrecan;",
    "ncbi_link": "ACAN: 11595
Aggrecan: 11595"
  },
  {
    "caption": "A, B qPCR for (A) Runx2 and (B) Col1A1 expression in HAC micromasses treated for 24 hours with recombinant GCP-2 (100 ng/ml) or vehicle (n=4); Runx2 = Runt-related transcription factor 2, Col1A1 = collagen type 1 alpha 1; n=4",
    "ncbi_link": "Col1A1: 1277
collagen type 1 alpha 1: 1277
Runx2: 860"
  },
  {
    "caption": "E qPCR for Col10A1 (n=3) of HAC 3 weeks after treatment with vehicle, T3 (100 ng/ml) or T3+GCP-2 (100 ng/ml); n=3;",
    "ncbi_link": "Col10A1: 1300"
  },
  {
    "caption": "D, E Maximum migratory activity of WT GCP-2 (50nM) was compared to GCP-2 mutants (50nM) in (D) chemotaxis and (E) trans-endothelial migration assays in CXCR2-expressing 300-19 pre B cells. WT = wildtype GCP-2; K101E = GCP-2_K101E single mutant; K105E = GCP-2_K105E single mutant; D = GCP-2_K101E_K105E double mutant; T = GCP-2_K100E_K101E_K105E triple mutant; n=4; p values were determined by fitting a generalised linear model followed by pairwise comparison of the estimated marginal means.",
    "ncbi_link": "GCP-2: 10844"
  },
  {
    "caption": "C28/I2 micromasses stimulated with WT GCP-2, GCP-2 triple mutant (GCP-2-T) or untreated and assessed for (F) AKT phosphorylation levels by western blotting; V = vehicle treated samples, GCP-2 = WT GCP-2 treated samples, GCP-2-T = triple mutant GCP-2 treated samples, pAKT = phosphorylated AKT, tAKT = total AKT. On the right, quantification of the density of the bands using ImageJ. Five independent experiments were analyzed. The data were scaled and p values were determined by fitting a generalised linear model followed by pairwise comparison of the estimated marginal means.",
    "ncbi_link": "GCP-2: 10844"
  },
  {
    "caption": "C28/I2 micromasses stimulated with WT GCP-2, GCP-2 triple mutant (GCP-2-T) or untreated and assessed G spectrophotometric quantification of proteoglycan content by Alcian blue staining. p values were determined by Kruskal-Wallis test with Dunn's post-hoc test; (n=8).",
    "ncbi_link": "GCP-2: 10844"
  },
  {
    "caption": "C28/I2 micromasses stimulated with WT GCP-2, GCP-2 triple mutant (GCP-2-T) or untreated and assessed H ACAN expression levels by qPCR; ACAN = Aggrecan; p values were determined by ANOVA with Tukey's HSD post-hoc test; n=4.",
    "ncbi_link": "ACAN: 176
Aggrecan: 176
GCP-2: 10844"
  },
  {
    "caption": "I-J Real time quantitative PCR of COL2A1 (I) and COL10A1 (J) mRNA normalized to β actin. p values were determined by fitting a generalised linear model followed by comparison of the estimated marginal means; n=4 control, 5 GCP-2 and GCP-2-T for COL2A1 and n=6 per group for COL10A1.",
    "ncbi_link": "β actin: 60
COL10A1: 1300
COL2A1: 1280
GCP-2: 10844"
  },
  {
    "caption": "K Number of neutrophils counted within the intercondylar space on sections from mice killed 4 days after an intra-articular injection of adenovirus encoding GFP (n= 3), GCP-2 (n=3) and GCP-2-T (n=3); p values were determined by fitting a generalised linear model (family=poisson) followed by pairwise comparison of the estimated marginal means.",
    "ncbi_link": "GFP: 
GCP-2: 74237"
  },
  {
    "caption": "B Weekly pain measurement by incapacitance, shown as the percentage of bodyweight loaded on the operated leg in GFP (n= 15) vs GCP-2 (n=14) and GFP vs GCP-2-T (n=15) treated mice. Circles show the mean, and error bars show 95% confidence intervals.",
    "ncbi_link": "GFP: 
GCP-2: 74237"
  },
  {
    "caption": "C Incapacitance at week 10 (final time-point); red line indicates 50% loading (no pain); p values were determined by unpaired, two-tailed one sample Student's t test testing the hypothesis that mice loaded 50% body weight on the operated limb (n=13 in the GFP group and n=14 in the GCP-2 and GCP-2-T groups). D The area under the curve (AUC) of incapacitance calculated starting from week 6; p values were determined by ANOVA with Tukey's HSD post-hoc test (n=13 in the GFP group and 14 in the GCP-2 and GCP-2-T group).",
    "ncbi_link": "GFP: 
GCP-2: 74237"
  },
  {
    "caption": "E, F Osteoarthritis severity assessed using (E) OARSI scoring system 10 weeks after MLI; GFP (n= 7), GCP-2 (n=8) and GCP-2-T (n=7); p values were determined by fitting a generalized linear model followed by comparison of the estimated marginal means. F representative image (Safranin O staining) for each treatment; arrows indicate the tidemark;",
    "ncbi_link": "GFP: 
GCP-2: 74237"
  },
  {
    "caption": "G Quantification of osteophytes area; GFP (n= 7), GCP-2 (n=7) and GCP-2-T (n=8); H Representative images with osteophyte highlighted I Osteophyte maturity score (n=7); p values were determined by fitting a generalized linear model followed by pairwise comparison of the estimated marginal means.",
    "ncbi_link": "GFP: 
GCP-2: 74237"
  },
  {
    "caption": "Photograph of male patient with FMR1G-ins. allele. Typical physical and behavioral features of FXS were noted in the patient, who shows moderate to severe intellectual disability.",
    "ncbi_link": "FMR1: 2332"
  },
  {
    "caption": "FMR1 mRNA levels were analyzed via RT-qPCR in EBV-transformed lymphocyte cells derived from the patient's blood samples. Patient cells showed a ˜60% decrease in FMR1 mRNA compared to control cells (*P = 0.010, 0.383 ± 0.110 SD, n = 3). Treatment with translational blocker puromycin restored FMR1 mRNA levels in patient cells (*P = 0.048, 0.383 ± 0.110 SD versus 1.25 ± 0.166 SD, n = 3), suggesting that the reduction of FMR1 mRNA in these cells is primarily due to nonsense-mediated decay. RT-qPCR reactions were run in triplicate in three independent experiments. Fold changes in FMR1 expression, normalized to HRPT expression, were calculated using the ΔΔCT method, and analyzed statistically with a two-tailed t-test (GraphPad). Error bars represent mean values with SD.",
    "ncbi_link": "HRPT: 
FMR1: 2332"
  },
  {
    "caption": "A-C HEK293 (A) and SH-Sy5y (B) cells, as well as primary neurons from FMR1 KO mice (C), were transfected with vectors encoding the GFP-tagged wild-type FMRP (GFP-FMR1WT) or the GFP-tagged patient FMRP (GFP-FMR1G-insertion) under the control of a β-actin promoter. Wild-type FMRP localizes predominantly in the cytoplasm, whereas the patient FMRP forms nuclear and nucleolar aggregates that colocalize with nucleophosmin. Scale bars in (A, B) represent 10 μm. Scale bar in (C) represents 5 μm.",
    "ncbi_link": "β-actin: 60
FMR1: 2332
FMR1: 14265"
  },
  {
    "caption": "Transfected HEK293 cells expressing a GFP-tagged FMRP in which the C-terminus is truncated following the G-ins. mutation site (GFP-FMR1ΔCt). GFP-FMR1ΔCt protein is exclusively cytoplasmic, suggesting that the truncation of the C-terminus alone is not sufficient to explain the localization change observed for the patientFMRP.Transfected HEK293 cells expressing a modified version of GFP-tagged patientFMRP (GFP-FMR1G-ins. [NLSmutated]). The novel amino acid sequence in the C-terminus of patientFMRP [RKRTRRKRTWRRLQRKRRSLPNR] contains stretches of arginines and lysines predicted to function as a nuclear localization signal (based on Expasy protein motif scanner, ScanProsite). Mutating adjacent R and K residues into alanines [RARTRAARTWARLQRAARSLPNR] abolishes the nucleolar localization of the patientFMRP, strongly suggesting that the novel amino acid sequence present in the patientFMRP C-terminus is a functional nuclear localization signal (NLS).",
    "ncbi_link": "FMR1: 2332"
  },
  {
    "caption": "Transfected HEK293 cells expressing GFP-tagged wild-type FMRP fused to the patient NLS motif (GFP-FMR1wt+NLS). Unlike the patient FMRP, GFP-FMR1wt+NLS protein is predominantly cytoplasmic and does not aggregate in the nucleus. However, treatment of HEK293 cells expressing GFP-FMR1wt+NLS with leptomycin B-an inhibitor of nuclear export-resulted in the appearance of nucleolar inclusions. This suggests that the presence of a full-length C-terminus facilitates the nuclear export of FMRP in this context.Transfected HEK293 cells expressing a modified version of GFP-tagged patient FMRP, in which the truncation of the C-terminus is reverted by restoring the open reading frame (GFP-FMR1G-ins.[Ct restored]). The patient protein is not detected in the nucleus when the C-terminus is intact; however, nucleolar retention of the protein is observed upon leptomycin B treatment of the transfected cells. In line with results from (A), this suggests that an intact C-terminus enables nuclear export of the FMR1 protein.Data information: Scale bar represents 10 μm.",
    "ncbi_link": "FMR1: 2332"
  },
  {
    "caption": "The morphology of small lateral ventral neurons (sLNvs) is sensitive to dfmr1 activity. Overexpression of wild-type dfmr1 in the sLNv neurons results in a consistent \"axonal collapse\" phenotype, where the branching of axonal termini of sLNvs is reduced. Scale bars represent 50 and 10 μm (magnified images).",
    "ncbi_link": "dfmr1: 37528"
  },
  {
    "caption": "Overexpression of wild-type dfmr1 (UAS-dfmr1wt) using a LNv neuron-specific driver line (Pdf-Gal4) causes reduction of branching area-\"axonal collapse\"-in the sLNv axonal termini. dfmr1ΔCt and dfmr1wt+NLS overexpression phenocopies overexpression of dfmr1wt, suggesting that the truncation of the C-terminus or the presence of the patient NLS alone does not impair or alter the functional efficacy of dfmr1 in this context. However, overexpression of dfmr1ΔCt+NLS fails to cause collapse of sLNv termini, indicating a significant loss or change of Dfmrp protein function. Axonal morphology is visualized by expressing CD8-GFP under the control of the same neuronal driver. Scale bar represents 10 μm.Quantification of axonal termini branching in LNv neurons overexpressing various dfmr1 alleles. Overexpression of dfmr1wt, dfmr1ΔCt, or dfmr1wt+NLS significantly reduced axonal branching area [****P < 0.0001; control 101.3 ± 29.76 SD, n = 30; UAS-dfmrwt 45.41 ± 21.69 SD, n = 29; UAS-dfmrΔCt 52.31 ± 14.67 SD, n = 32; UAS-dfmrwt+NLS 72.45 ± 21.83 SD, n = 29; UAS-dfmrΔCt+NLS 117.8 ± 36.96 SD, n = 28]. dfmr1ΔCt+NLS overexpression does not result in a significant change of axonal branching area compared to the background control [Pdf-Gal4, UAS-GFP] (P = 0.672). For quantification purposes, each branching area (n) was manually outlined, starting from the first point of defasculation of the axonal bundle. These measurements were normalized for variability in brain size across samples using LNv commissure length measurements for each brain. Two-tailed t-tests using Welch's correction were then used to compare controls with mutant phenotypes (GraphPad). Error bars represent mean values with SD. Dots visible for box plots of UAS-dfmrwt and UAS-dfmrΔCt represent samples that outlier the whiskers.",
    "ncbi_link": "Gal4: 
dfmr: 37528
dfmr1: 37528
Dfmrp: 37528
Pdf: 43193"
  },
  {
    "caption": "Overexpression of dfmr1ΔCt+NLS results in aberrant axonal termini morphology. Axonal guidance defects were frequently observed (arrowheads) and scored manually for bifurcations of the axon bundle (9/48), tangling of axons in the termini (13/48), and apparent looping of axons (7/48).",
    "ncbi_link": "dfmr1: 37528"
  },
  {
    "caption": "A-D Subcellular localization of transgenically expressed dfmr1wt, dfmr1ΔCt, dfmr1wt+NLS, and dfmr1ΔCt+NLS proteins in LNv neurons. DfmrpΔCt+NLS shows nuclear localization (A), colocalizing with the genetically encoded nuclear marker RedStinger, while Dfmrpwt, DfmrpΔCt, and Dfmrpwt+NLS are predominantly cytoplasmic (B-D). These results suggest that an intact C-terminus can mediate the nuclear export of the Dfmrp protein. Scale bar represents 5 μm.",
    "ncbi_link": "dfmr1: 37528
Dfmrp: 37528"
  },
  {
    "caption": "(A) Kaplan-Meier  estimate of overall survival of patients diagnosed with primary melanoma stratified by  CCN4  transcript abundance, with patients at risk tabulated below graph, Original data obtained from SKCM arm of TCGA and stratified based on CCN4 mRNA expression (CCN4 high/positive > 1 FPKM: blue, CCN4 low/negative < 1 FPKM: red). P-value calculated using the Peto & Peto modified Gehan-Wilcoxon test.",
    "ncbi_link": "CCN4: 8840"
  },
  {
    "caption": "(B-E)  B16F0 knockout created with Homology-Directed Repair approach with controls for  puromycin selection (B16F0-Ctr) created with pBabe-puro retrovirus. YUMM1.7  knockout created with double nickase approach with KO1 and KO2 indicating two different clones. Wildtype (WT: red)  B16F0 (B,C) and  YUMM1.7 (D,E) cells and CCN4  knockout variants (KO1: blue, KO2: black) were subcutaneously injected into (B,D) C57BL/6 immunocompetent and (C,E) NSG immunocompromised mice. Tumor volumes measured by caliper as a function of  time after tumor challenge, with n expressed as the number of mice with tumors over the number of mice injected.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(B-I) Graphs summarizing the change in frequency of immune cells in the YUMM1.7 tumor microenvironment following CCN4 knockout (n=6 /group). (B) CD3+, (C) CD4+, (D) CD8+, (E) NK cells, (F) CD11c+ TAMs, (G)  TANs, (H)  DCs, and (I) MDSC. Statistical significance was assessed using a Student's t-test using six biological replicates with results annotated with *: 0.01 ",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(K) Kaplan-Meier summary of the fraction tumor free in a 2x2 factor experimental design (n = 5 / group), where Tet-on vector control (red) versus inducible mCCN4 vector (black) and in the presence (dotted lines) or absence (solid lines) of doxycycline were the two factors.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(M) Representative flow cytometry data of the frequency of tumor-infiltrating  MDSC (GR1+ CD11c−/lo : dotted box) from the live  CD45+ CD11b+ compartment isolated from  CCN4-induced rescue (ID mCCN4 +  Dox) and CCN4 knockout (YM1.7-KO1) YUMM1.7 tumors.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(E-H) Graphs summarizing G-MDSCs (E,G) and M-MDSCs (F,H) in the spleens of time-matched YUMM1.7-WT and CCN4 KO (KO1) tumor bearing mice  (n = 4/group) expressed as percentage of CD45+ (E,F) and total number per gram spleen (G,H). Statistical significance was assessed using a Student's t-test with results annotated with *: 0.01 tumor free mice.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(A) Cytokine, chemokine, and growth factor expression by YUMM1.7-WT and CCN4-KO cells in vitro assayed using R&D Systems' Mouse XL  Cytokine Array. Orange dots represent results for specific cytokine probes while blue dots represent positive and negative controls. Dotted lines enclose a null distribution estimated from positive and negative controls.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(J-K) Analysis of the extracellular acidification rate (ECAR) associated with (J) glycolysis and (K) glycolytic capacity assayed by Seahorse Analyzer in WT and CCN4-KO tumors (n ≥ 12 biological replicates/group) after 36 hours ex vivo. Statistical significance was assessed using a Student's t-test with results annotated with ***: p<0.001. Results of biological replicates summarized as mean ± SEM.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(A) ELISpot  for  IFNγ  release by CD8+ T cells using parental YUMM1.7 and CCN4-KO YUMM1.7  (KO1) cells as targets and different amount of in vivo activated CD8+ T cells. Statistical significance was assessed using a Student's t-test with results annotated with ***: p<0.001. Results of three biological replicates summarized as mean ± SEM. (B) ELISpot for IFNγ release by in vivo activated CD8+ T cells  with CCN4-inducible cells as targets in the presence or absence of 0.5 mg/ml doxycycline. Statistical significance was assessed using a Student's t-test with results annotated with ***: p<0.001. Results of biological replicates summarized as mean ± SEM.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(C) CD8+ T cells isolated from the  spleens of C57BL/6 mice that rejected  YUMM1.7  tumors were assayed by in vitro ELISpot using variants of the YUMM1.7 cell line as targets (WT YUMM1.7 (Ym1.7) - yellow, CCN4-KO YUMM1.7 (Ym1.7-KO1)- light green,  CCN4-KO YUMM1.7 with a blank inducible expression vector (Ym1.7-KO1-IDvector) - dark green and blue, CCN4-KO YUMM1.7 with a CCN4 inducible expression vector (Ym1.7-KO1-IDmCCN4) - purple and red). Representative images shown under indicated condition with scale bar indicating 1 mm. Variants containing the inducible expression vector were also cultured in the absence (dark green and purple) or presence of 0.5 μg/ml  doxycycline (blue and red).  CD8+ T cells expressing IFNγ  and TNFα were quantified following 24 hour co-culture (bar graph). Results shown as mean ± S.D. for three biological replicates. Statistical significance was assessed using a Student's t-test with results annotated with ***: p<0.001 and n.s.: p>0.05.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "(A) Average tumor volumes of mice bearing YUMM1.7-WT (squares and triangles) or CCN4-KO (KO1, circles and inverted triangles) tumors (n = 4 mice/group). Groups were treated with either  αPD1  (triangles and inverted triangles) or isotype control (squares and circles) antibodies when the tumors reached 100 mm3 (dotted line). Statistical significance at each time point was assessed using a Student's t-test with results annotated with *: 0.01 ",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "CD8+ T cells  expressing PD1 within the tumor and spleen  were assayed by  flow cytometry  in mice bearing WT and CCN4-KO YUMM1.7 tumors Results representative of three biological replicates and summarized as mean ± SD. Statistical significance was assessed using a Student's t-test.",
    "ncbi_link": "CCN4: 22402"
  },
  {
    "caption": "B Identification of RabGGTβ as a binding protein of PTAR1. Anti-FLAG immunoprecipitates from control HeLa S3 cells or FLAG-PTAR1-expressing HeLa S3 cells were analyzed by SDS-PAGE and silver staining. The 35 kDa protein was identified as RabGGTβ by mass spectrometry. The asterisk denotes a degradation product of FLAG-PTAR1.",
    "ncbi_link": "FLAG: 
PTAR1: 375743"
  },
  {
    "caption": "D Biotin-geranylation of recombinant Ykt6 by GGTase-III. Bacterially produced recombinant untagged Ykt6 (left) was incubated with buffer, GGTase-III, or RabGGTase in the absence or presence of BGPP for 30 min at 37ºC. Biotin-geranylated Ykt6 was detected",
    "ncbi_link": "Ykt6: 10652"
  },
  {
    "caption": "Geranylgeranylation of unprenyl WT Ykt6 and the site 1 or site 2 mutants by GGTase-III. WT and mutant Ykt6 proteins (5 μM each) were incubated with GGTase-III (100 nM) and 3H-GGPP (1 μM), and the amount of 3H-geranylgeranyl transferred to Ykt6 was quantified (mean ± SEM, n = 3).",
    "ncbi_link": "Ykt6: 10652"
  },
  {
    "caption": "A Immunoblot of cell lysates from WT HAP1 cells and PTAR1 KO HAP1 cells using anti-Ykt6 antibody. Note the slight difference in the gel mobility of Ykt6 (arrows).",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "C Prenylation status of Ykt6 in WT and PTAR1 KO cells. Recombinant Ykt6 samples and cell lysates of WT cells, PTAR1 KO cells, and PTAR1 KO cells stably expressing PTAR1 (KO + PTAR1) were separated by DOC-PAGE (upper) or SDS-PAGE (lower), and analyzed by immunoblotting with anti-Ykt6 antibody.",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "D In vitro reconstitution of Ykt6 double prenylation. Dialyzed cytosol prepared from PTAR1 KO HAP1 cells was incubated at 37ºC for the indicated times with recombinant GGTase-III (100 nM) or RabGGTase (100 nM) in the absence or presence of GGPP (10 μM). After incubation, reaction products were separated by DOC-PAGE (upper) or SDS-PAGE (lower), and analyzed by immunoblotting with anti-Ykt6 antibody.",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "A Representative confocal images of the Golgi apparatus in WT or PTAR1 KO HeLa cells. Cells were co-immunostained for GM130 (a cis-Golgi marker) and golgin-97 (a trans-Golgi marker). Images were deconvoluted using Huygens software. The lower panels show magnified images of the boxed region of the upper panels. Scale bars, 5 μm.",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "B Electron micrographs of the Golgi apparatus in WT or PTAR1 KO HAP1 cells. Arrows indicate Golgi stacks. Arrowheads indicate examples of unfused vesicles accumulated around the swollen Golgi cisternae in PTAR1 KO cells. Scale bars, 500 nm.",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "Defect in intra-Golgi trafficking in PTAR1 KO cells. (C) VSVG-GFP expressing WT and PTAR1 KO HeLa cells were cultured at 40ºC and then shifted to 32ºC. VSVG-GFP fluorescence images taken at the indicated times after the temperature shift are shown. The right panel shows quantification of VSVG-GFP fluorescence in the Golgi region after the temperature shift (mean ± SEM, n = 6).",
    "ncbi_link": "GFP: 
PTAR1: 375743
VSVG: 1489834"
  },
  {
    "caption": "Defect in intra-Golgi trafficking in PTAR1 KO cells. (D) VSVG-GFP expressing WT HeLa cells, PTAR1 KO HeLa cells, and PTAR1 KO HeLa cells stably expressing PTAR1 (KO + PTAR1) were cultured at 40ºC and then shifted to 32ºC. At the indicated time points, cell surface proteins were biotinylated using sulfo-NHS-LC-biotin. Biotinylated VSVG-GFP was purified from cell lysates using avidin agarose and analyzed by immunoblotting with anti-GFP antibody. The right panel shows quantification of the cell surface biotinylated VSVG-GFP (means ± SEM, n = 3). Data were analyzed by one-way ANOVA with Dunnett's post-hoc test. *p < 0.05, ***p < 0.001.",
    "ncbi_link": "GFP: 
PTAR1: 375743
VSVG: 1489834"
  },
  {
    "caption": "E Analysis of LAMP1 glycosylation. Cell lysates of WT HeLa cells, PTAR1 KO HeLa cells, and PTAR1 KO HeLa cells stably expressing PTAR1 (KO + PTAR1) were analyzed by immunoblotting with anti-LAMP1 antibody (upper). Sialylated LAMP1 was precipitated from the cell lysates using Maackia amurensis leucoagglutinin (MAL) agarose and analyzed by immunoblotting (lower).",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "F Defect in the Golgi SNARE assembly in PTAR1 KO cells. The Golgi SNARE complex was immunoprecipitated from NEM-treated WT HAP1 cells, PTAR1 KO HAP1 cells, and PTAR1 KO HAP1 cells stably expressing PTAR1 (KO + PTAR1) using control mouse IgG, anti-GS28 IgG, or anti-syntaxin 5 IgG. Immunoprecipitates were analyzed by immunoblotting with antibodies against syntaxin 5, GS28, GS15, and Ykt6. Syntaxin 5 has two isoforms with different translation initiation sites. Inputs were 20% (syntaxin 5, GS28, and GS15) and 2% (Ykt6). The data shown are representative of three independent experiments with similar results.",
    "ncbi_link": "PTAR1: 375743"
  },
  {
    "caption": "E‐G Relative mtDNA level (E), MitoSox fluorescence (F) and TMRM fluorescence (G) of cells stably expressing AOX or empty vector, as indicated, after 5 days of treatment with dsRNA against CG2968, as shown. Note that these cells were cultured in the presence of hygromycin to maintain the AOX‐expressing or control plasmid.",
    "ncbi_link": "AOX: 5656847
CG2968: 31950"
  },
  {
    "caption": "H Indicated parameters, following 5 days of treatment with dsRNA against CG2968, in cells grown in galactose‐containing (Gal) medium.",
    "ncbi_link": "CG2968: 31950"
  },
  {
    "caption": "D. Western blot of total protein extracts from control S2 cells and cells treated with dsRNAs against GFP or CG2968 (cV), probed for NDUFS3 (cI), ATP synthase subunit α (cV) and GAPDH (loading control).",
    "ncbi_link": "CG2968: 31950"
  },
  {
    "caption": "(C) GFP-LC3 CHO cells were preincubated for 30 min in the presence or absence of 10 µM H89, and then they were incubated for 2 h with 1 mM dbcAMP to verify the activity of H89. Afterwards, cells were lysed with sample buffer and the samples were subjected to Western blot analysis using a rabbit anti-phosphoCREB and the corresponding HRP-labeled secondary antibody, and subsequently developed with an enhanced chemiluminescence detection kit. The band intensities were quantified with the Adobe Photoshop program (lower panel). These data are representative of two independent experiments.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "(A) GFP-LC3 CHO cells were preincubated with 10 µM 8-pCPT-2′-O-Me-cAMP (8-pCPT) for 30 min and then they were treated for 4 h with 10 µg/ml of α-hemolysin (Hla) or subjected to starvation conditions (Stv). Cells without any treatment were used as control. Cells were immediately analyzed by confocal microscopy. Quantification of the percentage of cells presenting LC3 puncta upon incubation under the different conditions is shown in the right panel (n = 50 cells/condition). These data are representative of two independent experiments.",
    "ncbi_link": "LC3: 362245///64862"
  },
  {
    "caption": "(B) CHO cells were cotransfected with GFP-LC3 and myc-EPAC wt (left panel) or myc-ΔEPAC (right panel). Twenty-four hours after transfection they were incubated for 2 h in starvation medium (Stv) or treated for 4 h with 10 µg/ml of α-hemolysin (Hla). Cells without any treatment were used as control (Ctr). Cells were analyzed by confocal microscopy. Images are representative of two independent experiments. (C) Quantification of the percentage of cells presenting LC3 puncta upon incubation under the different conditions (n = 20 cells/condition). These data are representative of two independent experiments",
    "ncbi_link": "EPAC: 
LC3: 64862///362245"
  },
  {
    "caption": "(A) CHO cells were cotransfected with RFP-LC3 and GFP-Rap2b wt (left panel) or GFP-Rap2b ΔAAX (right panel). Twenty-four hours after transfection, they were incubated for 2 h in starvation medium (Stv), with 50 ng/µl of rapamycin (Rapa) in full nutrient media, or treated for 4 h with 10 µg/ml of α-hemolysin (Hla). Cells without any treatment were used as control (Ctr). Cells were analyzed by confocal microscopy. Images are representative of three independent experiments.",
    "ncbi_link": "Rap2b: 5912"
  },
  {
    "caption": "(C) CHO cells were transfected with GFP-Rap2b wt or GFP-Rap2b ΔAAX and incubated with complete medium without (Ctr) or with 10 µg/ml of α-hemolysin (Hla) for 4 h, with 50 ng/µl of rapamycin (Rapa) or subjected to starvation conditions (Stv) for 2 h in the absence or presence of bafilomycin A1. Afterwards, cells were lysed with sample buffer and the samples were subjected to Western blot analysis using a rabbit anti-LC3 and the corresponding HRP-labeled secondary antibody, and subsequently developed with an enhanced chemiluminescence detection kit. These data are representative of two independent experiments.",
    "ncbi_link": "Rap2b: 5912"
  },
  {
    "caption": "(A) HeLa cells were cotransfected with Rap2b siRNA and GFP-LC3 (right panel) or irrelevant siRNA and GFP-LC3 (left panel). Forty-eight hours after transfection, they were incubated for 2 h in starvation medium (Stv), with 50 ng/µl of rapamycin (Rapa) or treated for 4 h with 10 µg/ml of α-hemolysin (Hla). Cells without any treatment were used as control (Ctr). Cells were analyzed by confocal microscopy. Images are representative of two independent experiments.",
    "ncbi_link": "LC3: 362245///64862
Rap2b: 5912"
  },
  {
    "caption": "(C) Upper panel: The knockdown of Rap2b was determined by Western blot as indicated in Materials and Methods. Lower panel: The band intensities of two independent experiments were quantified with the Adobe Photoshop program, and normalized against tubulin. * p<0.05 (paired Student's t-test).",
    "ncbi_link": "Rap2b: 5912"
  },
  {
    "caption": "(D) HeLa cells were cotransfected with GFP-LC3 and Rap2b siRNA or an irrelevant siRNA and incubated for 4 h with complete medium in the absence (Ctr) or presence of 10 µg/ml of α-hemolysin (Hla), with 50 ng/µl of rapamycin (Rapa) or subjected to starvation conditions (Stv) for 2 h. Afterwards, cells were lysed with sample buffer and the samples were subjected to Western blot analysis using a rabbit anti-LC3 and the corresponding HRP-labeled secondary antibody, and subsequently developed with an enhanced chemiluminescence detection kit. These data are representative of two independent experiments.",
    "ncbi_link": "LC3: 64862///362245
Rap2b: 5912"
  },
  {
    "caption": "cAMP cannot inhibit the autophagy induced by the toxin in cells overexpressing the Rap2b negative mutant.(A) CHO cells were cotransfected with RFP-LC3 and GFP-Rap2b ΔAAX. Twenty-four hours after transfection they were incubated for 2 h in starvation medium (Stv) or treated for 4 h with 10 µg/ml of α-hemolysin (Hla) in the presence (right panels) or absence of 1 mM dbcAMP (left panels). Cells without any treatment were used as control (Ctr). Cells were analyzed by confocal microscopy. Images are representative of two independent experiments. (B) Quantification of the percentage of cells presenting LC3 puncta (i.e., stimulated cells) upon incubation with the different conditions. These data are representative of two independent experiments.",
    "ncbi_link": "LC3: 362245///64862
Rap2b: 5912"
  },
  {
    "caption": "CHO cells were cotransfected with GFP-LC3 and myc-EPAC wt (upper panel) or myc-ΔEPAC (lower panel). Twenty-four hours after transfection, they were infected for 4 h with the wt strain of S. aureus (wt), the mutant deficient for α-hemolysin (Hla−), or the Hla(−) mutant expressing an α-hemolysin plasmid (Hla(−)+pHla). The nucleus and the bacteria were labeled with TOPRO as indicated in Materials and Methods and immediately visualized by confocal microscopy. Images are representative of three independent experiments.",
    "ncbi_link": "EPAC: 
LC3: 64862///362245"
  },
  {
    "caption": "(C) Quantification of the percentage of bacteria decorated with EPAC in cells infected with S. aureus. ** p<0.01 (paired Student's t-test, n = 20 cells/condition). These data are representative of three independent experiments.",
    "ncbi_link": "EPAC: "
  },
  {
    "caption": "(A) CHO cells were cotransfected with RFP-LC3 and GFP-Rap2b wt (upper panel) or GFP-Rap2b ΔAAX (lower panel). Twenty-four hours after transfection, they were infected for 4 h with the wt strain of S. aureus (wt), the mutant deficient for α-hemolysin (Hla−), or the Hla(−) mutant expressing an α-hemolysin plasmid (Hla(−)+pHla). The nucleus and the bacteria were labeled with TOPRO as indicated in Materials and Methods and immediately visualized by confocal microscopy. These data are representative of three independent experiments.",
    "ncbi_link": "LC3: 64862///362245
Rap2b: 5912"
  },
  {
    "caption": "Maximal cytoplasmic [Ca2+] in single, freshly sorted NKT1 and NKT2 cells following TCR stimulation in the presence or absence of BTP2 (1uM);",
    "ncbi_link": "TCR: 110067///110066///21473"
  },
  {
    "caption": "F A representative micrograph using widefield and deconvolution microscopy of HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 and immunostained for endogenous GM130. Scale bars are 5 μm and 2 μm (zoomed inset).",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "J HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 were treated with Baf A1 for 6 hours and immunostained for endogenous LAMP1. Scale bars are 5 μm for the confocal microscopy images and 2 μm for the airyscans.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "B GST pulldown assay of transiently transfected Myc-CALCOCO1 from HEK293 cell extracts with recombinant GST-tagged ATG8 family proteins. GST and GST fusions were visualized by Ponceau S staining (bottom panel), and co-precipitated Myc-CALCOCO1 detected by immunoblotting with anti-Myc antibody (upper panel).",
    "ncbi_link": "Myc: 
CALCOCO1: 57658"
  },
  {
    "caption": "GST pulldown assays of indicated in vitro transcribed/translated 35S-Myc-CALCOCO1 constructs with indicated recombinant GST-tagged ATG8 family proteins. Precipitated GST and GST fusions and co-precipitated Myc-CALCOCO1 constructs were analyzed as in A.",
    "ncbi_link": "Myc: 
CALCOCO1: 57658"
  },
  {
    "caption": "I GST pulldown assay of endogenous GABARAP from HEK293 cell extracts with recombinant GST-tagged CALCOCO1 constructs. GST and GST fusions were visualized as in A, and co-precipitated GABARAP with anti-GABARAP antibody (upper panel).",
    "ncbi_link": "GST: 
CALCOCO1: 57658"
  },
  {
    "caption": "Immunoblot analysis of HeLa CALCOCO1 KO cell lines stably transfected with WT EGFP-CALCOCO1 or EGFP-CALCOCO1 mLIR+∆623-691. Cells were induced with tetracycline for 24 hours and then starved or treated with MG132 or Baf A1 as indicated. The blot panels are from more than one western blot experiment but for clarity, only a single actin/GAPDH loading control is shown. In F, the bars represent the mean±sd of band intensities relative to the actin or GAPDH loading controls of three independent experiments quantified using ImageJ. Statistical comparison was analyzed by one-way ANOVA followed by Tukey multiple comparison test and significance displayed as ***p ˂ 0.001, *p ˂ 0.01; ns is not significant.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "G HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 or EGFP-CALCOCO1 mLIR+∆623-691 grown in full medium and treated with Baf A1 as indicated were immunostained for endogenous p62 and LC3B. Scale bars, 5 μm.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 were starved for 4 hours and then immunostained with anti-ATG13 and anti-WIPI2 antibodies. Scale bars in A are 5 μm for the confocal microscopy images and 2 μm for the airyscans.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "Immunoblot analysis of indicated cell lines treated as indicated. Numbers below the blots represent relative intensity of the bands in the shown blots normalized against the loading control (GAPDH The asterisk in K indicates that endogenous CALCOCO1 is detected in WT and KO cell extracts and EGFP-CALCOCO1 in cells extracts from the rescued cells. In the bars represent the mean±sd of band intensities relative to the actin or GAPDH loading control as quantified using ImageJ, n=5 in I, n=3 in others. Statistical comparison was analyzed by one-way ANOVA and significance displayed as ***p ˂ 0.001, **p ˂ 0.005, *p ˂ 0.01; ns is not significant.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "B Co- IP of Myc-VAPA or Myc-VAPB with EGFP-CALCOCO1 from transiently transfected HEK293 cells. The asterisks (*) indicate Myc-VAP previously detected on the same membrane",
    "ncbi_link": "EGFP: 
Myc: 
CALCOCO1: 57658
VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "E HeLa cells transiently co-transfected with EGFP-CALCOCO1 and Myc-VAPA or -VAPB were immunostained with anti-Myc antibody. Scale bars, 5 μm.",
    "ncbi_link": "EGFP: 
Myc: 
CALCOCO1: 57658
VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "F HeLa KO CALCOCO1 cells were transiently co-transfected with EGFP-CALCOCO1 and Myc-VAPA or Myc-VAPB, and then immunostained with anti-Myc and anti-LC3B antibodies. Arrows indicate dots of co-localization of all three proteins. Scale bars, 5 μm for large merged images and 1 μm for zoomed images.",
    "ncbi_link": "EGFP: 
Myc: 
CALCOCO1: 57658
VAPA: 9218
VAPB: 9217"
  },
  {
    "caption": "A, B Immunoblot analysis of HeLa WT and HeLa CALCOCO1 KO cells. The cells were starved for 6 hours (HBSS) as indicated and treated with Baf A1 as indicated. Numbers below the blots in A represent relative intensity of the bands in the shown blots normalized against GAPDH loading control. In A, the panels are collected from more than one western blot experiment but for clarity, only a single GAPDH loading control is shown. In B, the bars represent the mean±sd of band intensities of three independent experiments as quantified using ImageJ. Statistical comparison was analyzed by one-way ANOVA followed by Tukey multiple comparison test and significance displayed as **p ˂ 0.005, *p ˂ 0.01; ns is not significant.",
    "ncbi_link": "CALCOCO1: 57658"
  },
  {
    "caption": "C, D Immunoblot analysis of HeLa CALCOCO1 KO cell lines reconstituted with EGFP-CALCOCO1. Expression of EGFP-CALCOCO1 was induced or not with tetracycline and the cells were treated with MG132 or Baf A1 as indicated. Numbers below the blots in C represent relative intensity of the bands in the shown blots normalized against actin loading control. In C, the panels are collected from more than one western blot experiment but only a single actin loading control is shown. In D, the bars represent the mean±sd of band intensities of three independent experiments as quantified using ImageJ. Statistical comparison was analyzed as in B and significance displayed as **p ˂ 0.005, *p ˂ 0.01; ns is not significant.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "E HeLa CALCOCO1 KO cell lines reconstituted with EGFP-CALCOCO1 were treated with tetracycline or not to induce expression of EGFP-CALCOCO1. Abundance of the ER was quantified from widefield fluorescence images of endogenous RTN3 staining (see Materials and methods). Data are presented as mean ± sd of three independent experiments. Statistical comparison was analyzed as in B and significance displayed as ***p ˂ 0.001, **p ˂ 0.005, *p ˂ 0.01; ns is not significant.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "H, I Immunoblot analysis of HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 in fed or starved conditions and transfected with the indicated VAPA/B siRNAs.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658
VAPA: 9218"
  },
  {
    "caption": "A Immunoblot analysis of HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 in fed or starved conditions and treated as indicated with Baf A1 or PI3KC3 inhibitor SAR405.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "B Immunoblot analysis of HeLa CALCOCO1 KO cells stably expressing EGFP-CALCOCO1 mLIR+∆623-691 for 24 hours or not, and then treated as indicated.",
    "ncbi_link": "EGFP: 
CALCOCO1: 57658"
  },
  {
    "caption": "C, Representative confocal images of HeLa CALCOCO1 KO cells transiently co-transfected with mCherry-CALCOCO1, Myc-VAPA and EGFP-LAMP1, and then treated as indicated before immunostaining with anti-Myc anti-body. Arrows indicate co-localization. Scale bars in C, 5 μm for large merged images and 1 μm for zoomed images.",
    "ncbi_link": "EGFP: 
LAMP1: 
mCherry: 
Myc: 
CALCOCO1: 57658
VAPA: 9218"
  },
  {
    "caption": "A, B Hypocotyl length of ChWT, (A) RNAi-ChHFR1 transgenic and (B) chfr1 mutant seedlings grown under different R:FR. Seedlings were grown for 7 days in continuous W (R:FR>1.5) or for 3 days in W then transferred to W supplemented with increasing amounts of FR (W+FR) for 4 more days, producing various R:FR. Aspect of representative 7-day old ChWT, RNAi-HFR1 and chfr1-1 seedlings grown in W or W+FR (R:FR, 0.02), as indicated, is shown in lower panel. Data information: Values are the means ± SE of three independent biological replicates relative to ChWT value at 0 h. Asterisks mark significant differences (Student t-test: ** p-value <0.01; * p-value <0.05) relative to ChWT value at the same time point.",
    "ncbi_link": "HFR1: 
hfr1: "
  },
  {
    "caption": "C, D Effect of W+FR exposure on the expression of PIL1, YUC8 and XTR7 genes in seedlings of ChWT, (C) RNAi-HFR1 and (D) chfr1 mutant lines. Expression was analyzed in 7-day old W-grown seedlings transferred to W+FR (R:FR, 0.02) for 0, 1, 4, 8 and 12 h. Transcript abundance is normalized to EF1α levels. Data information: Values are the means ± SE of three independent biological replicates relative to ChWT value at 0 h. Asterisks mark significant differences (Student t-test: ** p-value <0.01; * p-value <0.05) relative to ChWT value at the same time point.",
    "ncbi_link": "EF1α: 
hfr1: 
XTR7: 
YUC8: 
HFR1: 
PIL1: "
  },
  {
    "caption": "Seedlings of ChWT and AtWT were grown for 3 days in W then either kept under the same conditions or transferred to W+FR (R:FR, 0.02) for the indicated times. Plant material was harvested every 24 h. Transcript abundance of HFR1 and PIF7 was normalized to three reference genes (EF1α, SPC25, and YLS8). Expression values are the means ± SE of three independent biological replicates relative to the data of AtWT grown in continuous W at day 3. Asterisks mark significant differences (2-way ANOVA: ** p-value <0.01, *** p-value <0.001) between ChWT and AtWT when grown under W (black asterisks) or W+FR (red asterisks).",
    "ncbi_link": "EF1α: 
SPC25: 825735
HFR1: 839300
PIF7: 836248
YLS8: 830725"
  },
  {
    "caption": "B Relative expression of HFR1 in seedlings of AtWT, At hfr1-5, hfr1>pAt:ChHFR1 (in blue) and hfr1>pAt:AtHFR1 (in red) lines grown under W+FR (R:FR, 0.02). Expression values are the means ± SE of three independent biological replicates relative to the data of 7 days old AtWT. Transcript abundance is normalized to UBQ10 levels. Data information: Different letters denote significant differences (one-way ANOVA with Tukey test, p-value <0.05) among means.",
    "ncbi_link": "HFR1: 
HFR1: 839300
hfr1: 839300
UBQ10: 825880"
  },
  {
    "caption": "D Relative HFR1 protein levels in seedlings of the indicated lines, normalized to actin protein levels, are the means ± SE of three independent biological replicates relative to hfr1>pAt:ChHFR1 line #22 that is taken as 1. Seedlings were grown for 7 days in continuous W (~20 µmol m-2 s-1) after which they were incubated for 3 h in high W (~100 µmol m-2 s-1) and transferred to W+FR (R:FR, 0.06) for 3 h. Data information: Different letters denote significant differences (one-way ANOVA with Tukey test, p-value <0.05) among means.",
    "ncbi_link": "HFR1: 
hfr1: 839300"
  },
  {
    "caption": "A Expression of HFR1 and protein levels of HFR1-3xHA in seedlings of hfr1>pAt:ChHFR1 (line #22) and hfr1>pAt:AtHFR1 (line #13). Seedlings were grown for 7 days in continuous W (~20 µmol m-2 s-1) after which they were incubated for 3 h in high W (~100 µmol m-2 s-1) and then either kept at high W or transferred to W+FR (R:FR, 0.06) for 3 or 6 h, as indicated in the cartoon at the top. Relative HFR1 transcript levels, normalized to UBQ10, are the means ± SE of three independent biological replicates relative to hfr1>pAt:ChHFR1 #22 grown for 3 h under W+FR. Relative protein levels, normalized to actin, are the means ± SE of three independent biological replicates relative to hfr1>pAt:ChHFR1 #22. Samples were collected at data points marked in the cartoon with asterisks.",
    "ncbi_link": "HFR1: 
HFR1: 839300
hfr1: 839300
UBQ10: 825880"
  },
  {
    "caption": "C Relative HFR1 transcript levels transiently expressed in tobacco leaves, normalized to the GFP, are the means ± SE of three independent biological replicates (left). Relative HFR1 protein levels, normalized to the GFP levels, are the means ± SE of four independent biological replicates (right). In A and C, asterisks mark significant differences (Student t-test: * p-value <0.05, ** p-value <0.01) between the indicated pairs.",
    "ncbi_link": "GFP: 
HFR1: 839300"
  },
  {
    "caption": "D Degradation of ChHFR1 (35S:ChHFR1) and AtHFR1 (35S:AtHFR1) in tobacco leaf discs treated with cycloheximide (CHX, 100 µM) for the indicated times. Tobacco plants were kept under high W (~200 µmol m-2 s-1) for 3 days after agroinfiltration and then leaf circles were treated with W+FR (R:FR, 0.2) and CHX. Relative HFR1 protein levels (ChHFR1, blue bars; AtHFR1, red bars), normalized to the GFP levels, are the means ± SE of four biological replicates relative to data point 0, taken as 1 for each line. Asterisks mark significant differences (2-way ANOVA: * p-value <0.05) between ChHFR1 and AtHFR1 at the same time point.",
    "ncbi_link": "HFR1: 
HFR1: 839300"
  },
  {
    "caption": "Hypocotyl length of seedlings of AtWT, (B) pif7-1, hfr1-5, pif7-1 hfr1-5 (top graph), pif7-2, hfr1-5 and pif7-2 hfr1-5 (bottom graph) mutants grown under different R:FR. Seedlings were grown in W (R:FR > 1.5) for 7 days or for 2 days in W and then transferred to two W+FR treatments (R:FR 0.06 or 0.02) for 5 additional days. Values of hypocotyl length are the means ± SE of three independent biological replicates (at least 10 seedlings per replica).",
    "ncbi_link": "hfr1: 839300
pif7: 836248"
  },
  {
    "caption": "C Hypocotyl length of seedlings of AtWT, (C) transgenic 35S:GFP-ΔNt-HFR1 (35S:ΔNt-HFR1), two lines of 35S:PIF7-CFP (35S:PIF7 #1 and #2), and 35S:GFP-ΔNt-HFR1 35S:PIF7-CFP double transgenic (35S:ΔNt-HFR1 x 35S:PIF7 #1 and #2) seedlings grown under different R:FR. Seedlings were grown in W (R:FR > 1.5) for 7 days or for 2 days in W and then transferred to two W+FR treatments (R:FR 0.06 or 0.02) for 5 additional days. Values of hypocotyl length are the means ± SE of three independent biological replicates (at least 10 seedlings per replica). D Aspect of representative 7-day-old W-grown seedlings shown in C. Scale bar is 1 cm.",
    "ncbi_link": "CFP: 
GFP: 
HFR1: 839300
PIF7: 836248"
  },
  {
    "caption": "C Hypocotyl length of seedlings of (left) AtWT, pifq, pif7-2, ChWT, (middle) 35S:GFP-ΔNt-HFR1 (ΔNtHFR1), hfr1-5 and (right) chfr1-1 and chfr1-2 lines grown at warm temperatures. Hypocotyl lengths are the means ± SE of three biological replicates. Asterisks mark significant differences (Student t-test: * p-value <0.05, ** p-value <0.01) relative to the same genotype grown at 22ºC (left and right graphs, black asterisks), and between the indicated pairs (middle graph, red asterisks).",
    "ncbi_link": "GFP: 
hfr1: 
HFR1: 839300
hfr1: 839300
pif7: 836248"
  },
  {
    "caption": "F Relative chlorophylls levels of (left) AtWT, pifq, ChWT, (middle) ΔNtHFR1, hfr1-5 and (right) chfr1-1 and chfr1-2 lines after DIS was promoted for the indicated time. For each genotype, values are relative to pigment levels at time 0 (7 days in W). Data are the means ± SE of four independent biological replicates.",
    "ncbi_link": "hfr1: 
HFR1: 839300
hfr1: 839300"
  },
  {
    "caption": "G Aspect of 4-day old dark-grown seedlings of AtWT, pifq, pif7-2, hfr1-5 and ΔNt-HFR1 (left panel), and AtWT, ChWT and chfr1-1 (right panel).",
    "ncbi_link": "hfr1: 
hfr1: 839300
HFR1: 839300
pif7: 836248"
  },
  {
    "caption": "(B) Nemo−/− MEFs were transfected with HA-tagged IKK subunits and HA-tagged M45 or an unrelated MCMV control protein ( m142), respectively. IP and IB were performed using anti-HA and anti-Flag antibodies, respectively. WCL were immunoblotted with anti-NEMO antibody and as described for panel A.",
    "ncbi_link": "Nemo: 16151"
  },
  {
    "caption": "(C) rip1−/− MEFs were transfected with HA-tagged M45 or an unrelated MCMV control protein (m142) and Flag-tagged NEMO. IP was done with an anti-HA antibody. Immunoprecipitates and WCL were analyzed by immunoblotting using the indicated antibodies.",
    "ncbi_link": "rip1: 19765"
  },
  {
    "caption": "(A) atg5−/− and atg5+/+ MEFs were mock infected or infected with MCMVΔM45 or the revertant virus, RM45, at an MOI of 10. Eight hpi cells were harvested and levels of the indicated proteins were analyzed by immunoblotting.",
    "ncbi_link": "atg5: 11793"
  },
  {
    "caption": "(A) NIH-3T3 cells stably expressing GFP-LC3 were transduced with retroviral vectors expressing M45 or Ct3. Three days later, cells were analyzed by confocal laser scanning microscopy. GFP-LC3 dots were counted in 50 cells per sample. Results are shown as box and whisker plots. The bottom and top of the box represent the first and third quartile, respectively. The horizontal line within the box represents the median. The minima and maxima within 1.5-fold interquartile range are shown as whiskers. Dots represent outliers. Significance was determined using ANOVA (***, p<0.001). M45 and Ct3 were detected by immunoblot",
    "ncbi_link": "LC3: 440738///81631///84557"
  },
  {
    "caption": "Quantification of mitotic defects as in (B) of H2B-mNeon-expressing HeLaEGFP-AID-CENATAC cells treated as indicated (three or five biological replicates, >85 cells in total per condition). For 2xZF the four zinc-finger cysteines were mutated to alanines; for Δ1-4 the corresponding motif was removed.",
    "ncbi_link": "EGFP: 
AID: 57379
CENATAC: 338657"
  },
  {
    "caption": "Representative stills of HeLaEGFP-AID-CENATAC cells expressing H2B-mNeon and depleted of CENATAC. Microtubules were visualized with SiR-Tubulin. Arrowheads and arrows indicate non-congressed chromosomes and supernumerary spindle poles, respectively. Scale bar, 5 μm. Time in hours. See Figure EV2 for the control condition. See also Movies EV1 and EV2. IAA, 3-indoleacetic acid.",
    "ncbi_link": "EGFP: 
AID: 57379
CENATAC: 338657"
  },
  {
    "caption": "Graph of fold-changes of proteins enriched (P-value < 0.05) in proteomics analysis of CENATAC vs. control co-immunoprecipitations of HeLaEGFP-CENATAC cells (three biological replicates). Splicing factors are depicted in orange. See also Appendix Figure S7.",
    "ncbi_link": "EGFP: 
CENATAC: 338657"
  },
  {
    "caption": "RT-PCRs of IPO5, SUDS3 and ZCCHC8 minor and adjacent major introns on RNA extracted from patient lymphoblasts or HeLaEGFP-AID-CENATAC cells depleted of GAPDH or CENATAC as indicated. u, unspliced; s, spliced.",
    "ncbi_link": "EGFP: 
AID: 57379
CENATAC: 338657
GAPDH: 2597
IPO5: 3843
SUDS3: 64426
ZCCHC8: 55596"
  },
  {
    "caption": "RT-PCRs of ZRSR2 and GAPDH (to visualize ZRSR2 knockdown efficiency, upper) and RT-PCRs of SUDS3 minor intron 7 (middle) and major intron 5 (lower) on RNA extracted from HeLaEGFP-AID-CENATAC or DLD-1 cells depleted of GAPDH or ZRSR2 as indicated.",
    "ncbi_link": "EGFP: 
AID: 57379
CENATAC: 338657
GAPDH: 2597
SUDS3: 64426
ZRSR2: 8233"
  },
  {
    "caption": "RT-PCR of major (U2-type) AT-AC introns in SYCP2 (intron 5) and TAF2 (intron 1), and minor (U12-type) AT-AC intron in IPO5 (intron 21) on RNA extracted from HeLaEGFP-AID-CENATAC cells depleted of GAPDH or CENATAC. Schematic representations of unspliced/spliced PCR products are depicted on the right.",
    "ncbi_link": "EGFP: 
AID: 57379
CENATAC: 338657
GAPDH: 2597
IPO5: 3843
SYCP2: 10388
TAF2: 6873"
  },
  {
    "caption": "C. RBM3 E3a regulation is conserved in humans. HEK293 cells were incubated at the indicated temperatures for 12h (DMSO/CHX last 4h) and investigated for E3a inclusion as in B (mean ± s.d., n= 3, all individual data points are shown).",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "A. CRISPR/CAS9 mediated removal of RBM3 E3a. One of two guide RNAs targeting the upstream intron (#1, #2) were co-transfected with a guide RNA targeting the downstream intron (#3). Below, genotyping PCR after clonal selection with px459 transfected cells serving as a negative control.",
    "ncbi_link": "CRISPR: 
CAS9: 69900935
RBM3: 5935"
  },
  {
    "caption": "RT-qPCR (B) analysis of RBM3 levels in edited cell lines. Clonal cell lines from A were incubated at the indicated temperatures for 24h. In B, isolated RNA was investigated by qPCR and rbm3 expression is shown relative to gapdh levels.",
    "ncbi_link": "gapdh: 2597
RBM3: 5935
rbm3: 5935"
  },
  {
    "caption": "Manipulation of RBM3 E3a splicing directly controls RBM3 expression levels. In D, HEK293 cells were transfected for 48h at 37°C with a MO blocking the 5'ss of E3a. RBM3 expression is shown relative to GAPDH levels and normalized to a non-targeting MO (n= 4-6, line indicates median, whiskers min to max, all individual data points are shown).",
    "ncbi_link": "GAPDH: 2597
RBM3: 5935"
  },
  {
    "caption": "Manipulation of RBM3 E3a splicing directly controls RBM3 expression levels. In E, primary hippocampal neurons were transfected with the indicated MOs for 48 hours and investigated for RBM3 by Western blotting. GAPDH served as a loading control (n= 3; line indicates median, whiskers min to max, all individual data points are shown).",
    "ncbi_link": "RBM3: 19652"
  },
  {
    "caption": "D. ASOs targeting M2-9, M4-7 or the 5'ss (see Figure EV4A and Table EV2) prevent endogenous RBM3 E3a inclusion in human HeLa cells. ASO-transfected cells were kept for 24 hours at 40°C. Control samples at 37°C and 40°C are shown; CHX was added for the last 4 hours. Exon 3a inclusion was investigated by splicing sensitive RT-PCR, a representative gel and phosphorimager quantification are shown (mean ± s.d., n= 3). The hashtag marks the use of internal 5' and 3'ss that is promoted by all ASOs targeting the M4 region. ASOs targeting the 5'ss induced the usage of an internal 5'ss (marked by two asterisks).",
    "ncbi_link": "RBM3: 5935"
  },
  {
    "caption": "M2D induces RBM3 mRNA (E) expression in human HeLa cells. ASOs were transfected for 24 hours at 37°C (grey) or at 40°C (red). RBM3 induction was measured relative to GAPDH expression (mean ± s.d., n= 3, all individual data points are shown).",
    "ncbi_link": "GAPDH: 2597
RBM3: 5935"
  },
  {
    "caption": "F. Total PrP and proteinase K-resistant PrPSc  levels in NBH-injected mice and in prion-diseased mice injected with control - or M2D ASOs. PrPSc levels are unaffected by M2D-mediated RBM3 induction.",
    "ncbi_link": "RBM3: 19652"
  },
  {
    "caption": "(C) Immunoblotting (IB) of ENKD1 and α-tubulin in wild-type and Enkd1 knockout mice.",
    "ncbi_link": "Enkd1: 102124"
  },
  {
    "caption": "(G-H) ERG recording images (G) and a-b wave amplitudes (H, n = 5 mice) show the difference in the ERG a-b wave amplitude between wild-type and Enkd1 knockout mice.",
    "ncbi_link": "Enkd1: 102124"
  },
  {
    "caption": "(I-J) VEP recording images (I) and N2-P2 wave amplitudes (J, n = 5 mice) show the difference in the VEP N2-P2 wave amplitude between wild-type and Enkd1 knockout mice.",
    "ncbi_link": "Enkd1: 102124"
  },
  {
    "caption": "(N-Q) Images (N) and quantification of the percentage of flagellated sperm (O, n = 9 mice), flagellar length (P, n = 100 sperm from nine mice), and the percentage of sperm with normal motility among flagellated sperm (Q, n = 9 mice) for wild-type and Enkd1 knockout mice. To quantify the percentage of flagellated sperm (O), >200 sperm were analyzed for each mouse. To quantify the percentage of sperm with normal motility among flagellated sperm (Q), >200 flagellated sperm were analyzed for each mouse. In panel N, the arrows indicate two spermatozoa without tails. Scale bar, 50 µm.",
    "ncbi_link": "Enkd1: 102124"
  },
  {
    "caption": "(E) Immunoblot analysis of ENKD1 and β-actin in RPE1 cells transfected with control or ENKD1 siRNAs and cultured in serum-free medium for 48 h.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "Immunofluorescence images (F) and quantification of the percentage of ciliated cells (G, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium, and stained with antibodies against acetylated α-tubulin and γ-tubulin and DAPI. To quantify the percentage of ciliated cells (G), >150 cells were analyzed for each experiment. Scale bar, 5 µm.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "quantification of ciliary length (H, n = 100 cilia from three independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(I, J) Immunofluorescence images (I) and quantification of the percentage of ciliated cells (J, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium, and stained with antibodies against Arl13b and Centrin and DAPI. To quantify the percentage of ciliated cells (J), >80 cells were analyzed for each experiment. Scale bar, 2 µm.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(K, L) Immunofluorescence images (K) and quantification of the percentage of ciliated cells (L, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs and plasmids expressing GFP, GFP-ENKD1, GFP-ENKD1-N, GFP-ENKD1-M, or GFP-ENKD1-C, cultured in serum-free medium, and stained with the antibody against acetylated α-tubulin and DAPI. The siRNA-resistant forms of ENKD1 were used for these rescue experiments. To quantify the percentage of ciliated cells (L), >120 cells were analyzed for each experiment. Scale bar, 3 µm.",
    "ncbi_link": "GFP: 
ENKD1: 84080"
  },
  {
    "caption": "(I) Immunofluorescence images of RPE1 cells transfected with GFP-ENKD1 or GFP vector, cultured in a serum-starved condition, and stained with the antibody against acetylated α-tubulin and DAPI. Scale bar, 1 µm.",
    "ncbi_link": "GFP: 
ENKD1: 84080"
  },
  {
    "caption": "Immunofluorescence images (B) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium, and stained with antibodies against CP110 and acetylated α-tubulin and DAPI.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "quantification of the percentage of cells with one CP110 dot (C, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs To quantify the percentage of cells with one CP110 dot (C), >120 cells were analyzed for each experiment.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(D, E) Immunofluorescence images (D) and quantification of the percentage of cells with one CEP97 dot (E, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium, and stained with antibodies against CEP97 and acetylated α-tubulin and DAPI. To quantify the percentage of cells with one CEP97 dot (E), >150 cells were analyzed for each experiment. Scale bar, 1 µm.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(F-H) Immunoblot analysis (F), immunofluorescence images (G), and quantification of the percentage of cells with one CP110 dot (H, n = 3 independent experiments) for RPE1 cells transfected with control or ENKD1 siRNAs, cultured in serum-free medium for 120 h, and stained with antibodies against CP110 and acetylated α-tubulin and DAPI. To quantify the percentage of cells with one CP110 dot (C), >80 cells were analyzed for each experiment. Scale bar, 1 µm.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(D) Immunoblot analysis of CP110 and β-actin in RPE1 cells transfected with control or CP110 siRNAs and cultured in serum-free medium for 48 h.",
    "ncbi_link": "CP110: 9738"
  },
  {
    "caption": "(G, H) Immunoprecipitation and immunoblotting (G) and quantification (H, n = 3 mice) showing the CP110-CEP97 interaction in the retinal tissues of wild-type and Enkd1 knockout mice. The intensity of each CEP97 band was normalized to that of the β-actin band.",
    "ncbi_link": "Enkd1: 102124"
  },
  {
    "caption": "(I, J) Immunoprecipitation and immunoblotting (I) and quantification (J, n = 3 independent experiments) showing the CP110-CEP97 interaction in serum-starved RPE1 cells transfected with control or ENKD1 siRNAs. The intensity of each CEP97 band was normalized to that of the β-actin band.",
    "ncbi_link": "ENKD1: 84080"
  },
  {
    "caption": "(B-D) Immunoprecipitation and immunoblotting showing the interaction of GFP-ENKD1 with Flag-CP110 (B and upper panel of D) or HA-CP110 (C and bottom panel of D) in HEK293T cells. Immunoprecipitation was performed with antibodies against GFP (B and C), Flag (upper panel of D), or HA (bottom panel of D).",
    "ncbi_link": "Flag: 
GFP: 
HA: 
CP110: 9738
ENKD1: 84080"
  },
  {
    "caption": "Decreased Drp1S616 phosphorylation in PINK1-null HEK293 cells Lysates of PINK1-null (PINK1KO) and parkin-null (parkinKO) HEK293 cells (a) and their matched wildtype controls (WT) were immuno-detected with antibodies against either phospho (Ser616)-Drp1 (pS616), phospho (Ser637)-Drp1 (pS637) or Drp1. β-actin was detected as a loading control. Quantitation of pS616/Drp1 for each experiment is shown Two independent PINK1KO and parkinKO HEK293 cell lines (1, 2) were shown. Student's test. *p<0.05, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 65018
parkin: 5071"
  },
  {
    "caption": "Decreased Drp1S616 phosphorylation in PINK1-null MEF cells Lysates of PINK1-null (PINK1KO) and parkin-null (parkinKO) MEF cells (c) and their matched wildtype controls (WT) were immuno-detected with antibodies against either phospho (Ser616)-Drp1 (pS616), phospho (Ser637)-Drp1 (pS637) or Drp1. β-actin was detected as a loading control. Quantitation of pS616/Drp1 for each experiment is shown Student's test. *p<0.05, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 68943
parkin: 50873"
  },
  {
    "caption": "Decreased Drp1S616 phosphorylation in PINK1-null mouse substantial nigra tissues. Lysates of PINK1-null (PINK1KO) and parkin-null (parkinKO) mouse substantial nigra tissues (e), and their matched wildtype controls (WT) were immuno-detected with antibodies against either phospho (Ser616)-Drp1 (pS616), phospho (Ser637)-Drp1 (pS637) or Drp1. β-actin was detected as a loading control. Quantitation of pS616/Drp1 for each experiment is shown Two independent PINK1KO and parkinKO substantial nigra from two separate PINK1KO and parkinKO mice (1, 2) were shown. Student's test. *p<0.05, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 68943
parkin: 50873"
  },
  {
    "caption": "(g, h). Overexpression of PINK1, not PINK1 kinase mutants, reverses Drp1S616 phosphorylation in PINK1KO HEK293 cells. Lysates of PINK1KO and PINK1WT control (WT) HEK293 cells expressing PINK1 variants were immuno-detected with an anti-phospho(Ser616)-Drp1 antibody (pS616), an anti-Drp1 antibody (Drp1) and an anti-PINK1 antibody (PINK1). Cells with mock transfection (Blank) and transfected with an empty plasmid (3.1) were included as controls (g). Quantitation of pS616/Drp1 is shown (h). PINK1: wildtype PINK1; D384N: PINK1 kinase-dead mutant; G309D, pathogenic PINK1 mutant; ∆110: PINK1 mito-target deficient mutant. Student's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(i, j). PINK1 deficiency does not affect expression and kinase activity of CDK1 and ERK1/2. Lysates of PINK1KO and PINK1WT control (WT) HEK293 cells were immuno-detected with an anti-phospho(Ser616)-Drp1 antibody (pS616), an anti-Drp1 antibody (Drp1), an anti-PINK1 antibody (PINK1), an anti-CDK1 antibody(CDK1), an anti-p44/p42 MAPK antibody (ERK1/2), an anti-phospho(Thr161)-CDK1 antibody (pThr161), and an anti-phospho(Thr202/204)-p44/p42 MAPK antibody (pThr202/204). β-actin was detected as a loading control (i). Quantitation of CDK1Thr161 phosphorylation (pThr161) and ERK1/2Thr202/204 phosphorylation (pThr202/204) was shown (j). Student's test. ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(n, o). Label-free relative quantitative mass spectrum analysis of Drp1S616 phosphorylation. Representative spectra for the Drp1 phospho-peptide (S616) SKPIPMPA(p)SPQK and non-phospho-peptide SKPIPMPA(p)SPQK. Spectra obtained for peptides from PINK1WT HEK293 cells are shown (n). The relative ratios of the phospho-peptides containing phosphor-Ser616 to peptides containing Ser616 from PINK1WT and PINK1KO HEK293 samples were calculated and plotted (o).",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(a, b). Decreased Drp1S616 phosphorylation in PINK1-null primary neurons. Lysates of DIV6 neurons generated from PINK1KO and PINK1WT control mice were immune-detected with antibodies against either phospho (Ser616)-Drp1 (pS616) or Drp1. Tuj1 was detected as a loading control (a). Quantitation of pS616/Drp1 for each experiment is shown (b). Student's test. **p<0.01. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(c, d). TEM analysis of mitochondria in mouse substantial nigra. Sections of substantial nigra from 18-month-old PINK1KO and PINK1WT control mice were analyzed under TEM (c, left panels, scale bar=2 µm). Amplified images of mitochondria from dot line frames gated region are shown (c, right panels, scale bar=1 µm). Asterisks indicate abnormal elongated mitochondria. A quantitative analysis of mitochondria with perimeter >2µm is shown (d). Over 300 identifiable mitochondria (cristae and/or double membrane) per mice were randomly and blindly selected for perimeter measurement. Student's test. *p<0.05. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 68943"
  },
  {
    "caption": "(e, f). Overexpression of Drp1WT, but not phosphorylation mutant Drp1S616A, suppresses mitochondrial fusion in dendrites of PINK1KO primary neurons. (e). DIV4 neurons generated from PINK1 WT control or PINK1KO mice were co-transfected mito-GFP with either pcDNA3.1 (3.1) or Drp1WT or Drp1S616A. Neurons were immuno-detected with an antibody against myc-tag (Myc) (red, to detect exogenous Drp1). Mito-GFP: green, to detect mitochondria. Representative images were shown, scale bar=25 μm. Magnified dendritic shafts gated by a dot line frame are shown (Zoom, right panels, scale bar=5 μm).(f). Quantification of Mito-index in dendrites of neurons from experiments of (e). 10 neurons were randomly selected and analyzed in each experiment. One-way ANOVA followed with Tukey's test. *p<0.05, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "Drp1: 74006
Drp1: 10059
PINK1: 68943"
  },
  {
    "caption": "(a-c). Drp1 is required for mitochondrial fission induced by PINK1. Drp1-null HeLa cells (Drp1KO) and their wildtype controls (Drp1WT) were co-transfected Δ110-PINK1-GFP-FKBP with FRB-MTS. Cells were induced with 250 nM rapalog for 2 hours to activate PINK1 kinase, followed by immunodetecting mitochondria (TOM20, red) and Δ110-PINK1-GFP-FKBP /FRB-MTS (Δ110-PINK1, green). Nuclei were labeled with DAPI (blue). Cells treated with solvent (DMSO) were used as a treatment control. Representative images were shown (a, upper panel, scale bar=25 μm). Higher magnification images are also included (a, lower panel, scale bar=10 μm). Mitochondrial morphology in different transfections was quantified. (b, c). Student's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
Drp1: 10059
PINK1: 65018"
  },
  {
    "caption": "(d-f). Drp1S616 phosphorylation is required for mitochondrial fission induced by PINK1. Drp1KO HeLa cells were co-transfected Δ110-PINK1-GFP-FKBP /FRB-MTS with either a plasmid encoding Drp1WT or a Drp1 dephosphorylation mimic mutant Drp1S616A. Cells were treated with 250 nM rapalog for 2 hours to activate PINK1 kinase, followed by immunodetecting mitochondria (TOM20, blue), exogenous Drp1 (myc, red), Δ110-PINK1-GFP-FKBP /FRB-MTS (PINK1-FKBP, green). Cells treated with solvent (DMSO) were used as a treatment control. Representative images were shown, scale bar=25 μm (d). Higher magnification images are also included (d, Zoom, scale bar=5 μm). Mitochondrial morphology in different transfections was quantified (e, f). Student's test. **p<0.01, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
Drp1: 10059
PINK1: 65018"
  },
  {
    "caption": "(g, h). Targeting PINK1 kinase domain to OMM increases mitochondrial localization of phosphorylated Drp1S616. HEK293 cells co-transfected FRB-MTS with Δ110-PINK1-GFP-FKBP were treated with 250 nM rapalog (Rapalog). After 2hours treatment, cytosol protion (cyto) and mitochondria (Mito) were fractionated and immunobloted with antibodies against either phospho (Ser616)-Drp1 (pS616), Drp1 (Drp1), or GFP (PINK1). Tom20 and β-actin were detected as mitochondrial loading control and cytosol loading control, respectively (g). Quantitation of pS616/Drp1 in various conditions was shown (h). Student's test. **p<0.01, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
PINK1: 65018"
  },
  {
    "caption": "(i, j). Targeting PINK1 kinase domain to the OMM increases mitochondrial localization of Drp1. HeLa cells co-transfected FRB-MTS with Δ110-PINK1-GFP-FKBP (FKBP-PINK1) were treated with 250 nM rapalog (Rapalog) for 2 hours to activate PINK1 kinase. Cells treated with solvent (DMSO) were included as a control. Cells were immunostained with antibodies against either Tom20, Drp1 and GFP (PINK1-FKBP). Representative images were shown, scale bar=2 μm (i). Higher magnification images from gated box are shown (bottom panels). Arrows indicate Drp1 puncta. Mitochondria-associated (yellow) and non-associated Drp1(Red) are shown, scale bar=1 μm. Mitochondria-associated Drp1 puncta were analyzed by using an ImageJ plugin-Coloc 2 and expressed as the Manders' Colocalization Coefficients (MCC) (j). Three different regions from each cell and >15 cells for each experimental group were analyzed. Student's test. **p<0.01. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
PINK1: 65018"
  },
  {
    "caption": "(k, l). PINK1 regulates S616 and S637 phosphorylation of Drp1 via independent mechanisms. DRP1KO HEK293 cells co-transfected FRB-MTS/Δ110-PINK1-GFP-FKBP (PINK1WT) with either myc-Drp1WT or myc-Drp1S616A were treated with 250 nM rapalog (Rapalog) for 2 hours to activate PINK1 kinase. Cells treated with solvent (DMSO) were included as a control. Cell lysates were immunoblotting with antibodies against either phospho (Ser616)-Drp1 (pS616), phospho-(Ser637)-Drp1 (pS637), Drp1 and GFP (to detect PINK1-FKBP) (k). β-actin was detected as a loading control. Quantitation of pS637/Drp1 in various conditions was shown (l). One-way ANOVA followed with Tukey's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
myc: 
DRP1: 10059
Drp1: 10059
PINK1: 65018"
  },
  {
    "caption": "(a-e). ATG5 is dispensable for PINK1-mediated mitochondrial fission. MEF cells derived from ATG5-null (ATG5KO) and their wildtype control mice (ATG5WT) were co-transfected Δ110-PINK1-GFP-FKBP /FRB-MTS with either PINK1WT or a kinase-dead mutant PINK1D384N. Cells were induced with 250 nM rapalog (Rapalog) for 2 hours to activate PINK1 kinase, followed by immunodetecting mitochondria (TOM20, red) and Δ110-PINK1-GFP-FKBP /FRB-MTS (PINK1-FKBP, green). Cells treated with solvent (DMSO) were used as a treatment control. Representative images are shown, scale bar=25 μm (a). Higher magnification images are also included (panels beneath the large cell images, scale bar=10 μm). Mitochondrial morphology in different transfections was quantified (b-e). Student's test. *p<0.05, ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.",
    "ncbi_link": "FKBP: 
FRB: 
GFP: 
MTS: 
ATG5: 11793
PINK1: 65018"
  },
  {
    "caption": "(f-i). Drp1 is dispensable for recruitment of parkin to mitochondria. Drp1WT and Drp1KO HeLa cells were transfected with GFP-parkin. Cells were treated with 20 μM CCCP for 2 hours (f) followed by immunodetecting mitochondria (TOM20, red) and parkin (GFP-parkin, green). Nuclei were labeled with DAPI (blue). Cells treated with solvent (DMSO) were used as a treatment control. Representative images were shown, scale bar=25 μm. Cell with mitochondrial parkin (%) in different experimental group was quantified (g, i). One-way ANOVA followed with Tukey's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.",
    "ncbi_link": "GFP: 
Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "(f-i). Drp1 is dispensable for recruitment of parkin to mitochondria. Drp1WT and Drp1KO HeLa cells were transfected with GFP-parkin. Cells were treated with 150 μM actinonin for 6 hours (h), followed by immunodetecting mitochondria (TOM20, red) and parkin (GFP-parkin, green). Nuclei were labeled with DAPI (blue). Cells treated with solvent (DMSO) were used as a treatment control. Representative images were shown, scale bar=25 μm. Cell with mitochondrial parkin (%) in different experimental group was quantified (g, i). One-way ANOVA followed with Tukey's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments. For each condition, >100 cells were analyzed.",
    "ncbi_link": "GFP: 
Drp1: 10059
parkin: 5071"
  },
  {
    "caption": "(a, b). Drp1WT and Drp1S616D, but not Drp1S616A, rescue PINK1-null induced crushed thorax in Drosophila. Representative thorax images of PINK1WT and PINK1-deficiency (PINK1KO) Drosophila expressing either mhc-gal4 (Mhc/+), mhc-gal4 driven human Drp1wt (Mhc>hDrp1WT) or mhc-gal4 driven human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven human Drp1S616D (Mhc>hDrp1S616D) are shown. Images were taken either under light microscopy (a, upper panels, yellow arrowhead indicates the collapsed throax) or SEM (b, lower panels). Quantitation of crushed thorax is shown (b). > 200 flies for each experiment are analyzed. Scale bar=200µm. One-way ANOVA followed with Tukey's test. ***p<0.001. Data was presented as mean ± SEM of three independent experiments. For each condition, >200 flies were quantified.",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(c) Drp1WT and Drp1S616D, but not Drp1S616A, restore abnormal ATP production in PINK1-null flies. ATP production was measured using muscle lysates generated from PINK1WT flies expressing mhc-gal4 (Mhc/+) (as a control) and PINK1KO flies expressing either mhc-gal4 (Mhc/+), mhc-gal4 driven human Drp1wt (Mhc>hDrp1wt) or mhc-gal4 driven human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven human Drp1S616D (Mhc>hDrp1S616D). One-way ANOVA followed with Tukey's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "Drp1WT and Drp1S616D, but not Drp1S616A, rescue mitochondrial structures in PINK1KO flies. Representative images of Mito-GFP (green) labeled mitochondria (d) from PINK1WT flies expressing mhc-gal4 (Mhc/+) (as a control) and PINK1KO flies expressing either mhc-gal4 (Mhc/+), Mhc-gal4 driven human Drp1wt (Mhc>hDrp1wt) or Mhc-gal4 driven human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven human Drp1S616D (Mhc>hDrp1S616D) are shown. Scale bar=10 μm (d) Average mitochondrial size was quantified, >3 flies/group and 3-6 pictures of different microscopic fields from each fly were analyzed per repeat. One-way ANOVA followed with Tukey's test. *p<0.05, ***p<0.001. Data was presented as mean ± SEM of three independent experiments (e).",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "Drp1WT and Drp1S616D, but not Drp1S616A, rescue mitochondrial structures in PINK1KO flies. Representative images of TEM analysis (f) of IFMs from PINK1WT flies expressing mhc-gal4 (Mhc/+) (as a control) and PINK1KO flies expressing either mhc-gal4 (Mhc/+), Mhc-gal4 driven human Drp1wt (Mhc>hDrp1wt) or Mhc-gal4 driven human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven human Drp1S616D (Mhc>hDrp1S616D) are shown. Scale bar= 1 μm (f). Average mitochondrial size was quantified, >3 flies/group and 3-6 pictures of different microscopic fields from each fly were analyzed per repeat. Normal and abnormal mitochondrial number per mm2 were quantified. >3 flies/group and 3-6 pictures of different microscopic fields from each fly were analyzed per repeat. Bars represent the mean ± SEM of three independent experiments (g).",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(h, i). Drp1WT and Drp1S616D, but not Drp1S616A, suppress cell death in PINK1KO flies. Representative TUNEL staining (Red) images of IFM sections from PINK1WT and PINK1KO flies expressing either Mhc-gal4 (Mhc/+), Mhc-gal4 driven human Drp1wt (Mhc>hDrp1WT) or Mhc-gal4 driven human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven human Drp1S616D (Mhc>hDrp1S616D) are shown. Nuclei were counter-stained with DAPI (blue), scale bar=10 μm. Apoptotic cells (%) in different genotype flies were quantified (i). >5 flies/group and 3-6 pictures of different microscopic fields from each fly were analyzed per repeat.One-way ANOVA followed with Tukey's test. ***p<0.001. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(j). Expression and phosphorylation of hDrp1 in Drosophila. Fly muscle lysates generated from PINK1WT or PINK1KO flies expressing mhc-gal4 driven hDrp1WT (WT) and hDrp1S616A (S616A) were immunoblotted with antibodies against either phospho(Ser616)-Drp1(pS616) (to detect phosphorylated hDrp1S616), Drp1 (to detect both endogenous and exogenous Drp1), myc-tag (to detect exogenous Drp1). α-tubulin was detected as a loading control. Flies expressing mhc-gal4 (-) were included as an expression control.",
    "ncbi_link": "Drp1: 10059
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(a, b). Drp1 rescues PINK1KO induced collapsed thorax phenotype in dATG7-deficient Drosophila. Representative SEM images of thorax from PINK1WT, (upper panels) and PINK1KO (lower panels) flies combined with dATP7 deficiency (dATG7KO) or their controls (dATG7WT), followed by expressing either mhc-gal4 (Mhc/+) alone, or Mhc-gal4 driven expression of human Drp1 (Mhc>hDrp1WT), mhc-gal4 driven expression of human Drp1S616A (Mhc>hDrp1S616A) or mhc-gal4 driven expression of human Drp1S616D (Mhc>hDrp1S616D) are shown (a). Quantitation of crushed thorax in flies with indicated genotypes is presented (b). > 100 flies for each experiment are analyzed. Scale bar=200µm. One-way ANOVA followed with Tukey's test. ***p<0.001. Data was presented as mean ± SEM of three independent experiments. ",
    "ncbi_link": "ATG7: 37141
ATP7: 32142
Drp1: 10059
Drp1: 74006
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(c, d) Drp1 rescues PINK1KO induced mitochondrial defects in dATG7KO Drosophila. Representative TEM images of indirect flight muscle from PINK1WT (upper panels) and PINK1KO (lower panels) flies combined with dATG7KO or their controls (dATG7WT), followed by expressing either mhc-gal4 (Mhc/+) alone, or Mhc-gal4 driven expression of human Drp1(Mhc>hDrp1WT), mhc-gal4 driven expression of human Drp1S616A(Mhc>hDrp1S616A) or mhc-gal4 driven expression of human Drp1S616D(Mhc>hDrp1S616D) are shown (c). Scale bar=1 μm. Normal and abnormal mitochondrial number per mm2 from each experimental group were and quantified. >3 flies/group and 3-6 pictures of different microscopic fields from each fly were analyzed per repeat. Bars represent the mean ± SEM of three independent experiments (d).",
    "ncbi_link": "ATG7: 37141
Drp1: 10059
Drp1: 74006
gal4: 855828
PINK1: 31607"
  },
  {
    "caption": "(e). Drp1 rescues PINK1KO induced ATP reduction in Drosophila. ATP contents of thorax muscle tissues from the indicated genotypes were measured and normalized against the protein levels One-way ANOVA followed with Tukey's test. ***p<0.001, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "Drp1: 10059
PINK1: 31607"
  },
  {
    "caption": "(g, h). Reduction of Drp1S616 phosphorylation in dermal fibroblasts derived from PD patients with PINK1 mutations. Lysates of cells derived from three unrelated normal control individuals (Control, C) and four familial PD patients with PINK1 mutations (PINK1mutant) were immunoblotted with antibodies recognizing either phosphor-Drp1S616 (pS616) or Drp1 protein. β-actin was detected as a loading control (g). A quantitative analysis of phospho-Drp1S616 (pS616/Drp1) is shown (h). Student's test. **p<0.01, ns: no significance. Data was presented as mean ± SEM of three independent experiments.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "Human bronchial epithelial BEAS-2B cells were infected with the influenza A/Scotland/20/74 (H3N2) virus (IAV) at MOI=1 for 4 h, and subsequently treated or not with 4 mg/mL of succinate  (Suc) for 20 h. (e) Human bronchial epithelial BEAS-2B  cells were infected with a A/Scotland/20/74 (H3N2) virus  (IAV) carrying a wild-type NP  (NP  WT) or with the corresponding mutated virus bearing a NP  with a K87R substitution (NP  K87R). Cells were infected by either virus at MOI=1 for 4 h, then washed and treated or not with 4 mg/mL of succinate  for 20 h. Localization  of NP  proteins was analyzed by confocal immunofluorescence microscopy. Scale bar: 10 µM. Pictures are representative of three independent experiments. (f) Relative nuclear  intensity of NP  was determined by using the Intensity Ratio Nuclei Cytoplasm  Tool. Data information: Data are represented as the mean ± SEM of 3 biological replicates without 2 technical replicates each. at least 10 (f) random images were analysed per treatment with a minimum of 5 cells per field. Statistical analysis was performed using the Mann-Whitney test (*P < 0.05).",
    "ncbi_link": "NP: 3655155"
  },
  {
    "caption": "A. Levels of ROW protein in rowRNAi lines were decreased in both male and female fly heads. Western blot for the two rowRNAi lines compared to controls was performed using rat polyclonal αROW and rat αTUBULIN (TUB). Genotype description: rowRNAi-1(Act-GAL4/+; UAS-rowRNAi-1/+), rowRNAi-2(Act-GAL4/+; UAS-rowRNAi-2/+), rowRNAi-1 Control (CyO/+; UAS-rowRNAi-1/+), rowRNAi-2 Control (CyO/+; UAS- rowRNAi-2) and Act-GAL4 Control (Act-GAL4 /+).",
    "ncbi_link": "Act: 5656844
GAL4: 855828
row: 36685
CyO: 34350"
  },
  {
    "caption": "B. Decrease in the viability of rowRNAi lines. To examine the viability of rowRNAi flies, we counted the offspring generated from the cross between the heterozygous Act-GAL4/CyO driver line with the homozygotes rowRNAi, or WT (w1118) flies as control. Values are the percentages from the total progeny ± standard error of the mean (SEM).",
    "ncbi_link": "Act: 5656844
GAL4: 855828
row: 36685
CyO: 34350"
  },
  {
    "caption": "C. Decrease in pupal eclosion of rowRNAi line. Pupae were collected from the cross between the heterozygous Act-GAL4/CyO driver line with the homozygotes rowRNAi-1 or WT (w1118) flies as control. Values are the percentages for each genotype of pupal eclosion ± SEM.",
    "ncbi_link": "Act: 5656844
GAL4: 855828
row: 36685
CyO: 34350"
  },
  {
    "caption": "D. Survival curve for rowRNAi flies showing reduced life span compared to controls. n=3 (biological replicates). Significance was tested using the Kaplan-Meier estimate of survival and log-rank test.",
    "ncbi_link": "row: 36685"
  },
  {
    "caption": "E. Crossing of females/males rowRNAi flies with WT males/females (w1118) flies resulted in a strong reduction in offspring number. Values are the number of offspring from crosses between WT (w1118) flies and flies with different genotypes.",
    "ncbi_link": "row: 36685"
  },
  {
    "caption": "A. Western blot for flies expressing endogenous FLAG-tagged ROW (ROW-FLAG), with αFlag tag antibody to validate the tagging. αTubulin (TUB) antibody was used as a reference. Het, Heterozygotes; Hom, Homozygotes for tagged ROW.",
    "ncbi_link": "ROW: 36685"
  },
  {
    "caption": "D. BEAF-32 coimmunoprecipitate with ROW. Lysates from S2 cells not transfected (-) or transfected (+) with ROW-FLAG tagged plasmid were subjected to immunoprecipitation with αFlag tag beads. The immunoprecipitates and input (5%) were analyzed by western blot with αFlag tag and αBEAF-32 antibodies.",
    "ncbi_link": "FLAG: 
ROW: 36685"
  },
  {
    "caption": "D. ChIP-qPCR results using FLAG-tag antibody for S2 cells transfected with WT or AT-hook mutant ROW-FLAG tagged plasmids (n = 3, technical and biological replicates). As a control, cells not transfected with ROW-FLAG tagged plasmid were used. Input percentages for 3 biological replicates are shown for three promoters containing AT-rich sequences (Hcf, Phax, and Hcs).",
    "ncbi_link": "FLAG: 
Hcf: 43788
Hcs: 40659
Phax: 35926
ROW: 36685"
  },
  {
    "caption": "E. Co-IP results using αFlag antibody in S2 cells transfected with WT or AT-hook mutant ROW-FLAG tagged plasmids or with a plasmid containing only the ZNF domains of ROW (with FLAG-tag). As a control, cells not transfected with ROW-FLAG tagged plasmid were used. Western blot using αFLAG, αWOC, αBEAF-32, αHP1c, and αTUB (loading control) antibodies is shown for input and IP samples.",
    "ncbi_link": "FLAG: 
ROW: 36685"
  },
  {
    "caption": "(B) Quantitative analysis of AEP positive cells and C/EBPβ positive cells, respectively. The density of both AEP positive cells and C/EBPβ positive cells were significantly decreased through knocking down C/EBPβ or knocking out AEP in mice. Representative data of five samples, data are shown as mean± SEM. *P =0.0390 (*P < 0.05), ***P =0.0002 (***P < 0.001), ****P < 0.0001, one-way ANOVA. (C) Quantitative analysis of AT8 positive cells (left) and TauN368 positive cells (right), respectively. The density of both AT8 positive cells and TauN368 positive cells were significantly decreased through knocking down C/EBPβ or knocking out AEP in mice. n=5 in each group, data are shown as mean± SEM. *P =0.0194 (*P< 0.05), ***P =0.0001 (***P < 0.001), ****P < 0.0001, one-way ANOVA. (D) Quantitative analysis of Aβ positive cells (left) and APPC586 positive cells (right), respectively. The fluorescence intensity of Aβ positive cells and the density APPC586 positive cells were significantly decreased through knocking down C/EBPβ or knocking out AEP in mice. Representative data of five samples, data are shown as mean± SEM. *P=0.0107 (*P < 0.05), **P=0.0048 (3xTg vs 3xTg AEP KO), **P=0.0044 (3xTg vs WT) (**P< 0.01), ***P=0.0006 (***P< 0.001), ****P < 0.0001, one-way ANOVA. (E) Quantitative analysis of AT8 positive cells (upper) and T22 positive cells (lower), respectively. The fluorescence intensity of both AT8 positive cells and T22 positive cells were significantly decreased through knocking down C/EBPβ or knocking out AEP in mice. Representative data of five samples, data are shown as mean± SEM. **P=0.0014 (3xTg vs 3xTg C/EBPβ+/-), **P=0.0030 (3xTg vs 3xTg AEP KO) (**P<0.01), ***P=0.001, ****P<0.0001, one-way ANOVA.",
    "ncbi_link": "C/EBPβ: 12608
AEP: 19141"
  },
  {
    "caption": "(C) Detection of phosphorylation PIN2 by Phos-tag Western blotting. Arabidopsis plants (Col-0) were growth in ammonium as only nitrogen source, and treated with 5 mM KNO3 or 5mM KCl as control. Total protein from roots were analyzed in SDS PAGE using Phos-tag to detect changes in phosphorylation status. Immunoblotting was performed with PIN2 antibody. Total proteins isolated from eir1.1 roots were used as a negative control. White and red asterisks indicate a slow- or fast-mobility band corresponding to a more or less phosphorylated PIN2, respectively.",
    "ncbi_link": "eir1.1: 835813"
  },
  {
    "caption": "(D) Western blot against PIN2 protein comparing nitrate treated (KNO3) and control (KCl) condition in Arabidopsis roots for all genotypes (eir1-1 mutant background was complemented with PIN2::PIN2wt-GFP (PIN2wt), PIN2::PIN2S439D-GFP (PIN2S439D phospho-mimic point mutation) or PIN2::PIN2S439A-GFP (PIN2S439A, phospho-null point mutation).",
    "ncbi_link": "eir1-1: 835813
PIN2: 835813"
  },
  {
    "caption": "(A) Primary root length of Col-0 wild type plants or eir1-1 mutant plants was measured using the ImageJ program 3 days after 5 mM KNO3 or KCl treatments. Tukey box plot show results from 3 independent biological replicates per experimental condition (n = 10-15 roots each replicate). The box plot shows the data within the interquartile range (25th and 75th percentiles) and a solid black line represents the median. Whiskers show maximum and minimum values no further than 1.5x IQR (interquartile range). Outlier data are plotted individually. Asterisk indicates statistically significant difference between analyzed by unpaired, two-tailed and assuming equal variance t-test (** p < 0.01).",
    "ncbi_link": "eir1-1: 835813"
  },
  {
    "caption": "(B) Number of initiating and emerging lateral roots of Col-0 or eir1-1 mutant plants were counted using light microscopy 3 days after 5 mM KNO3 or KCl treatments. Tukey box plot show results from 3 independent biological replicates per experimental condition (n = 10-15 roots each replicate). The box plot shows the data within the interquartile range (25th and 75th percentiles) and a solid black line represents the median. Whiskers show maximum and minimum values no further than 1.5x IQR (interquartile range). Asterisk indicates statistically significant difference between analyzed by unpaired, two-tailed and assuming equal variance t-test (** p < 0.01).",
    "ncbi_link": "eir1-1: 835813"
  },
  {
    "caption": "(A) Confocal microscopy using Zeiss Airyscan microscope and Zeiss-blue3.1 software was used to visualize PIN2 in Arabidopsis roots. \"e\" denotes epidermis and \"c\" cortex. Scale bar = 20 µm. (B-D) Tuckey box plots show PIN2-GFP fluorescence intensity quantification (number of roots analyzed per experimental conditions = 8-10; arbitrary units, a.u.) at the total cell membrane in roots (B), and from epidermal (C) and cortex (D) plasma membrane in the different genotypes. The box plot shows the data within the interquartile range (25th and 75th percentiles) and a solid black line represents the median. Whiskers show maximum and minimum values no further than 1.5x IQR (interquartile range). Outlier data are plotted individually. Letters denote statistically significant difference between means as determined by one-way ANOVA analysis followed by Tukey HSD post hoc test (p < 0.05). ",
    "ncbi_link": "GFP: 
PIN2: 835813"
  },
  {
    "caption": "(A) Immunoblot  analysis of SP  in lysates from COS-7  cells which were untransfected, transfected with RFP-SP  + empty vector or co-transfected with SP-shRNA-GFP  + RFP-SP  (knock-down) or shRNA-resistant RFP-SP  (rescue). β-actin  and GFP  signals illustrate equal protein loading and SP-shRNA expression level, respectively. (B) Quantification of SP  expression from 6 different experiments, normalized to the  β-actin signal. *P < 0.05, ns, not significant, P > 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). Data information: Data represent mean ± SEM.",
    "ncbi_link": "GFP: 
RFP: 
SP: 
SP: 104027"
  },
  {
    "caption": "(C) Homer-DsRed  (green) and immunostained  endogenous SP  (red) in dendrites  from neurons  transfected with either empty vector, scramble shRNA or SP-shRNA with GFP  reporter (blue). Scale bar: 10 µm. (D) Average SP  intensity for same conditions (EV: n = 47; Scr-shRNA: n = 53; SP-shRNA: n = 62, n indicates the number of cells, from 3 cultures; normalized to empty vector condition). **P < 0.01, ****P < 0.0001 (Kruskal-Wallis test followed by Dunn's multiple comparison test). (E) Fraction of SP+ synapses  for same conditions. (EV: n = 47; Scr-shRNA: n = 53; SP-shRNA: n = 62, n indicates the number of cells from 3 cultures). *P < 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). Data information: Data represent mean ± SEM.",
    "ncbi_link": "GFP: 
SP: 60324"
  },
  {
    "caption": "(F) Homer1c-DsRed (red) and immunostained  surface AMPARs  (green) in dendrites  from neurons  transfected with either SP-shRNA-GFP  or empty vector (EV) with GFP   reporter (blue) and treated with TTX  or left untreated (UT). Scale bar: 5 µm. (G) AMPAR synaptic  fluorescence intensity normalized to untreated empty vector (EV) condition (EV: UT, n = 42, TTX, n = 33; SP-shRNA: UT, n = 30, TTX, n = 31, n indicates the number of cells, from 3 cultures). *P < 0.05, **P < 0.01, ns, not significant, P > 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). Data information: Data represent mean ± SEM.",
    "ncbi_link": "GFP: 
SP: 60324"
  },
  {
    "caption": "(A) Micrographs showing Homer1c-GFP  (green) and immunostaining  for surface AMPARs  (blue) and endogenous SP  (red) in neurons  transfected with miR-124  or control miR-67 (miR-Ctrl), and treated with TTX, or left untreated (UT). Scale bar: 5 µ (B) Percentage of SP+ synapses  for same conditions as in (A) (miR-Ctrl: UT, n = 25, TTX, n = 26; miR-124: UT, n = 30, TTX, n = 30, n indicates the number of cells, from 3 cultures). ****P < 0.0001, ns, not significant, P > 0.05 (two-way ANOVA test followed by Tukey's multiple comparison test). (C) Homer1c-GFP  intensity for same condition as in (A), normalized to untreated miR-Ctrl (miR-Ctrl: UT, n = 25, TTX, n = 26; miR-124: UT, n = 30, TTX, n = 30, n indicates the number of cells, from 3 cultures). ns, not significant, P > 0.05 (two-way ANOVA test followed by Tukey's multiple comparison test). (D) AMPAR synaptic  fluorescence intensity for same condition as in (A), normalized to untreated miR-Ctrl (miR-Ctrl: UT, n = 25, TTX, n = 26, miR-124: UT, n = 30, TTX, n = 30, n indicates the number of cells, from 3 cultures). ***P < 0.001, *P < 0.01, ns, not significant, P > 0.05 (two-way ANOVA test followed by Tukey's multiple comparison test). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "miR-67: 259740
miR-124: 70441///268755"
  },
  {
    "caption": "(A) Micrographs showing dendrites  from neurons  transfected with Homer1c-DsRed  (magenta) and SEP-GluA2  constructs containing wild-type (WT) or mutated (MUT) 3'UTR (green) and treated with TTX  for 48 h, or left untreated (UT). Scale bar: 10 µm. (B) SEP-GluA2 synaptic  fluorescence intensity for each condition, normalized to GluA2-3'UTR-WT untreated neurons  (3'UTR-WT: UT, n = 29, TTX, n = 37; 3'UTR-MUT: UT, n = 18, TTX, n = 14; n indicates the number of cells, from 3 cultures). *P < 0.05, ns, not significant, P > 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "SEP: 
GluA2: 29627"
  },
  {
    "caption": "(C) Micrographs showing dendrites  from neurons  transfected with Homer1c-BFP  (magenta), GFP-SP-shRNA (gray) and a rescue RFP-SP  construct containing wild-type (WT) or mutated (MUT) 3'UTR (geen) and treated with TTX, or left untreated (UT). Scale bar: 10 µm. (D) Percentage of SP+ synapses  for each condition (3'UTR-WT: UT, n = 26, TTX, n = 28; 3'UTR-MUT: UT, n = 26, TTX, n = 24; n indicates the number of cells, from 3 cultures). **P < 0.01, ***P < 0.001, ns, not significant, P > 0.05 (two-way ANOVA test followed by Tukey's multiple comparison test). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "GFP: 
RFP: 
SP: 104027
SP: 60324"
  },
  {
    "caption": "(E) Micrographs showing Homer1c-GFP  (magenta) and immunostaining  for surface AMPARs  (cyan) and endogenous SP  (green) in neurons  transfected with or without 50 nM SP TSB-LNA and treated with TTX, or left untreated (UT). Scale bar: 10 µm. (F) Percentage of SP+ synapses  for each condition (Control: UT, n = 36, TTX, n = 52; SP TSB-LNA: UT, n = 62, TTX, n = 29; n indicates the number of cells from 3 cultures). *P < 0.05, **P < 0.01, ns, not significant, P > 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). (G) AMPAR synaptic  fluorescence intensity for each condition, normalized to control untreated neurons  (Control: UT, n = 30, TTX, n = 36; SP TSB-LNA: UT, n = 37, TTX, n = 20; n indicates the number of cells from 2 cultures). *P < 0.05, ns, not significant, P > 0.05 (Kruskal-Wallis test followed by Dunn's multiple comparison test). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "SP: 60324"
  },
  {
    "caption": "(A) Confocal  images showing dendrites  from CA3 pyramidal cells  transfected with RFP-SP  (green) containing wild-type (WT) or mutated (MUT) 3'UTR + SP-shRNA-BFP  (magenta). Arrowheads indicate SP+ spines. Scale bar: 10 µm. (B) Graph plot showing spine head volume vs SP  integrated intensity (n = 5 cells). Each plot represents a single spine  for which SP  integrated intensity has been normalized to average SP  intensity of SP+ spines  in the same neuron. Plots for SP- and SP+ spines  appear in grey and magenta, respectively. The black dotted line represents linear regression (R2 = 0.25, P = 0.0004). (C) Paired data showing spine head volume for SP- vs SP+ spines. Each pair of plot represents average values for SP- vs SP+ spines  for a given neuron. *P = 0.0031 (two-tailed Student t test). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "BFP: 
SP: 60324"
  },
  {
    "caption": "(F) Higher magnification of dendritic spines from neurons  transfected with rescue RFP-SP  (magenta) containing wild-type (WT) or mutated (MUT) 3'UTR and BFP-shRNA-SP   (grey) and contacted by GFP-Syp+ terminals  (green). Arrowheads indicate putative synaptic  contacts. Scale bar: 5 μm. (G) Percentage of SP+ spines  in neurons  expressing RFP-SP-3'UTR-WT vs -MUT and depending on the apposition or not to a GFP-Syp+ terminal  (SP-3'UTR-WT: TetTx-, n = 220, TetTx+, n = 26; SP-3'UTR-MUT: TetTx-, n = 616, TetTx+, n = 25; n indicates the number of spines  from 5-7 pairs). (H) Spine head volume in same conditions as in (G) (SP-3'UTR-WT: TetTx-, n = 26, TetTx+, n = 26 spines  from 5 pairs, 4 slices; SP-3'UTR-MUT: TetTx-, n = 25, TetTx+, n = 25; n indicates the number of spines  from 7 pairs, 7 slices). ***P < 0.001, *P < 0.05, ns, not significant (Kruskall-Wallis test followed by Dunn's multiple test). (I) Cumulative probability distributions of spine head  volumes for TetTx- and TetTx+ spines  from neurons expressing RFP-SP-3'UTR-WT (SP-WT, light gray and light green) or RFP-SP-3'UTR-MUT (SP-MUT, dark gray and dark green). Data information: Data are represented as mean ± SEM.",
    "ncbi_link": "RFP: 
SP: 104027
TetTx: 24255210"
  },
  {
    "caption": "D. HeLa cells were transfected with Nup358 siRNA (siNup358) or Nup214 siRNA (siNup214). Cells were fixed and stained for endogenous Nup358 (green, upper panel) or Nup214 (green, lower panel) and endogenous P body marker (Dcp1a, red). Graph represents the quantitative data as mean ± SD. The data was obtained from three independent experiments, and in each experiment, 100 cells were counted from different fields for the presence of intact microscopically distinct P bodies and expressed as percentage.",
    "ncbi_link": "Nup214: 8021
Nup358: 5903"
  },
  {
    "caption": "D. HeLa cells were transfected with Nup358 siRNA (siNup358) or Nup214 siRNA (siNup214). Western blot (WB) indicates the extent of Nup358 depletion and the level of Dcp1a.",
    "ncbi_link": "Nup214: 8021
Nup358: 5903"
  },
  {
    "caption": "A. Western analysis of HeLa cells, treated with control (siControl), Dicer (siDicer), Nup214 (siNup214) or Nup358 (siNup358) siRNA, for assessing the extent of protein depletion using indicated antibodies. Vinculin was used as loading control.",
    "ncbi_link": "Dicer: 23405
Nup214: 8021
Nup358: 5903"
  },
  {
    "caption": "B. HeLa cells were initially transfected with indicated siRNAs, followed by renilla luciferase (RL) reporter constructs; RL-control (no let-7a binding site in the 3'UTR) or RL-3xBulge (3 imperfect let-7a binding sites in the 3'-UTR). Firefly luciferase (FL) was co-transfected to serve as internal control. RL/FL luminescence ratio was calculated. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "Firefly luciferase: 
renilla luciferase: 
let-7a: 406883///406882///406881"
  },
  {
    "caption": "C. HEK293T cells were transfected with indicated siRNAs, followed by pCMV-FL-miR30 (P) reporter with either pSUPER-control or pSUPER-miR30 constructs. RL was co-transfected as internal control. FL/RL luminescence ratio was calculated. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "miR30: "
  },
  {
    "caption": "D. HeLa cells were initially transfected with control (siControl), Dicer (siDicer) or Nup358 (siNup358) specific siRNAs, followed by FL constructs containing wild type (HMGA2-wt) or mutant (HMGA2-mut) HMGA2 3'-UTR, along with RL as internal control. Graph was plotted using data from three independent experiments. FL/RL luminescence ratio was calculated. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "Dicer: 23405
HMGA2: 8091
Nup358: 5903"
  },
  {
    "caption": "A. HeLa cells were transfected with control, Dicer or Nup358 specific siRNAs, as indicated. Upper panel, total RNA was isolated and analyzed by northern blotting for let-7a using radio-labeled probe. Ethidium bromide (EtBr) stained gel indicates equal loading of RNA samples.",
    "ncbi_link": "Dicer: 23405
let-7a: 406883///406882///406881
Nup358: 5903"
  },
  {
    "caption": "A. HeLa cells were transfected with control, Dicer or Nup358 specific siRNAs, as indicated. Bottom panel, total RNA was isolated from control, Dicer or Nup358 siRNA treated cells and was reverse-transcribed using TaqMan microRNA reverse transcription kit. The levels of let-7a were quantified by qPCR following manufacturer's instructions. Graph represents the relative levels of miRNAs as compared to U6 RNA control. The values were further normalized to let-7a levels in control siRNA knockdown condition. Data are presented as mean SD (n = 3).",
    "ncbi_link": "Dicer: 23405
let-7a: 406883///406882///406881
Nup358: 5903"
  },
  {
    "caption": "B. HeLa cells were transfected with indicated siRNAs, followed by RL-3xBulge construct. Immunoprecipitation (IP) was performed with control mouse IgG (IgG IP) or anti-AGO2 antibody (AGO2 IP) using lysates prepared from these cells. Total RNA was isolated from control and AGO2 immunoprecipitates and the levels of AGO2 associated let-7a (top left panel) and miR-17 (top right panel) were quantified by q-PCR. Graph represents the extent of miRNAs associated with AGO2 as compared to U6 RNA (as a negative control) with AGO2.",
    "ncbi_link": "miR-17: 406952
let-7a: 406883///406882///406881"
  },
  {
    "caption": "B. HeLa cells were transfected with indicated siRNAs, followed by RL-3xBulge construct. Immunoprecipitation (IP) was performed with control mouse IgG (IgG IP) or anti-AGO2 antibody (AGO2 IP) using lysates prepared from these cells. Bottom left panel; RNA isolated from IgG control or AGO2 immunoprecipitate samples was reverse-transcribed using oligo(dT) primer. RL-3xBulge mRNA association with AGO2 was quantified by q-PCR and normalized to the level of GAPDH mRNA associated with AGO2.",
    "ncbi_link": "GAPDH: 
AGO2: 27161"
  },
  {
    "caption": "B. HeLa cells were transfected with indicated siRNAs, followed by RL-3xBulge construct. Immunoprecipitation (IP) was performed with control mouse IgG (IgG IP) or anti-AGO2 antibody (AGO2 IP) using lysates prepared from these cells. Bottom right panel; AGO2 immunoprecipitates were analyzed by western blotting using AGO2 specific antibody. Vinculin was used as loading control. Data are presented as mean SD (n = 3).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "C. HeLa cells were transfected with control (siControl) or Nup358 specific siRNA (siNup358) for 96 h. Cells were lysed and subjected to immunoprecipitation with control IgG (IgG IP) or anti-AGO2 (AGO2 IP). Total RNA was extracted from initial lysate and IP samples and analyzed by q-PCR for validated miRNA targets, Serbp1 and Dnajb11. GAPDH was considered as negative control. Data expressed as the relative amount of target mRNA associated with AGO2 as compared to GAPDH mRNA.",
    "ncbi_link": "GAPDH: 
Dnajb11: 51726
Nup358: 5903
Serbp1: 26135"
  },
  {
    "caption": "C. HeLa cells were transfected with control (siControl) or Nup358 specific siRNA (siNup358) for 96 h. Western blots indicate the extent of Nup358 depletion and AGO2 immunoprecipitation in siControl and siNup358 samples. Vinculin was used as loading control. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "Nup358: 5903"
  },
  {
    "caption": "F. HeLa cells were transfected with RL-3xBulge construct and immunoprecipitation was performed using control (IgG-IP) or Nup358 (Nup358-IP) antibodies. Total RNA was isolated from the immunoprecipitates and analyzed for let-7a miRNA (left panel), RL-3xBulge mRNA and the endogenous miRNA target Dnajb11 using q-PCR (right panel). Fold enrichment in Nup358-IP as compared to IgG-control was calculated and the data are presented as mean SD (n = 3), P‐value was obtained using Student's t‐test.",
    "ncbi_link": "Dnajb11: 51726
let-7a: 406883///406882///406881"
  },
  {
    "caption": "B. HEK293T cells were co-transfected with GFP-maltose binding protein (MBP)-control or GFP-tagged version of indicated Nup358 fragments along with HA-AGO2. Immunoprecipitation (IP) was performed using GFP antibodies and the presence of AGO2 was detected by western blotting (WB) using HA antibodies.",
    "ncbi_link": "Nup358: 5903"
  },
  {
    "caption": "D. HEK293T cells transfected with GFP-MBP (control), GFP-Nup358-C or GFP-Nup358-CΔIR (a mutant devoid of IR region) and HA-AGO2. IP and WB analyses were performed as indicated.",
    "ncbi_link": "Nup358: 5903"
  },
  {
    "caption": "F. Lysates from cells expressing GFP-control, GFP-human (h) Nup358-IR or GFP-zebrafish (z) Nup358-IR and HA-AGO2 were immunoprecipitated using GFP antibodies and the immunoprecipitates were analyzed for the presence of HA-AGO2 by western blotting.",
    "ncbi_link": "Nup358: 
Nup358: 5903"
  },
  {
    "caption": "D. GFP-control, GFP-IR1+2 wild type or mutants were co-expressed with HA-AGO and IP and WB analysis were performed to detect the interaction using indicated antibodies.",
    "ncbi_link": "IR1: 11188"
  },
  {
    "caption": "A. Top panel; depicts the amino acid sequence corresponding to the Nup358-SIM1 region and substitutions introduced in the SIM1 mutant. Bottom panel: HEK293T cells were co-transfected with GFP-control, GFP-SIM1 or GFP-SIM1-mut along with HA-AGO2 and immunoprecipitation (IP) was performed with GFP specific antibodies and western analysis (WB) of the input lysate and immunoprecipitates were carried out using indicated antibodies.",
    "ncbi_link": "Nup358: 5903"
  },
  {
    "caption": "D. SIM1 directly interacts with AGO2. Bacterial lysates expressing MBP control or MBP-AGO2 and GST or GST-SIM1 were mixed and GST pull down assay was performed. The presence of proteins in the pull down samples was analyzed by WB using specific antibodies. The extent of GST pull down was monitored by coomassie staining of the membrane (coomassie).",
    "ncbi_link": "AGO2: 27161"
  },
  {
    "caption": "A. Left panel; HeLa cells were co-transfected with GFP-MBP (control), GFP-SIM1 or GFP-SIM1-mut (AGO interaction defective) along with RL-control or RL-3xbulge. Firefly luciferase was used as transfection control. Dual luciferase assay was performed. RL/FL luminescence ration was plotted after normalization with GFP-control. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "Firefly luciferase: "
  },
  {
    "caption": "B. Bottom left panel; HEK293T cells were co-transfected with indicated expression constructs and the RL reporter. Firefly luciferase (FL) was used as transfection control. Dual luciferase assay was performed. The ratio of RL/FL luminescence was plotted after normalization with N-HA-MBP control. Data are presented as mean SD (n = 3), P‐value was calculated using Student's t‐test.",
    "ncbi_link": "Firefly luciferase: "
  },
  {
    "caption": "C. Ectopic expression of AGO2 restores P body formation, but fails to rescue the impairment in miRNA function in Nup358 depleted cells. HeLa cells were transfected with control (siContriol) or Nup358 (siNup358) specific siRNA, followed by indicated constructs. Left panel: Quantitative representation showing the number of cells showing microscopically distinct P bodies in different indicated conditions. The data was obtained from three independent experiments, and in each experiment, 100 cells were counted from different fields for the presence of intact P bodies and expressed as percentage.",
    "ncbi_link": "AGO2: 27161
Nup358: 5903"
  },
  {
    "caption": "C. Ectopic expression of AGO2 restores P body formation, but fails to rescue the impairment in miRNA function in Nup358 depleted cells. HeLa cells were transfected with control (siContriol) or Nup358 (siNup358) specific siRNA, followed by indicated constructs. Middle panel: HeLa cells were transfected with indicated siRNAs, followed by expression constructs and miRNA RL reporters. FL was used as transfection control. The ratio of RL/FL luminescence was calculated. Data are presented as mean SD (n = 3), P‐value was obtained using Student's t‐test.",
    "ncbi_link": "AGO2: 27161
Nup358: 5903"
  },
  {
    "caption": "C. Ectopic expression of AGO2 restores P body formation, but fails to rescue the impairment in miRNA function in Nup358 depleted cells. HeLa cells were transfected with control (siContriol) or Nup358 (siNup358) specific siRNA, followed by indicated constructs. Right panel: Western blot analysis for the relative expression of indicated constructs in HEK293T cells. a-tubulin is used as loading control.",
    "ncbi_link": "AGO2: 27161
Nup358: 5903"
  },
  {
    "caption": "D. HeLa cells were transfected with siControl or siNup358 and subjected to membrane flotation assay. Fractions were collected and analyzed for the presence of indicated proteins by western blotting.",
    "ncbi_link": "Nup358: 5903"
  },
  {
    "caption": "B OsPRR73 confers salinity stress tolerance in  rice. The seedlings of Dongjin (DJ, the wild type control), osprr73, and the complementation line of  osprr73 (abbreviated as Com-L1) grown under 12 h light/12 h dark conditions for 28 days (left panel), transferred to 180 mM NaCl  for 21 days (middle panel) and recovered for 12 and 24 days (the two right panels) respectively. Scale bar, 5 cm. C Statistical analysis of the survival rate of DJ, osprr73 and Com-L1  plants in (B) after recovery 12 days. Data are presented as mean ± SD. (n from 4 biological replicates, and 24 plants were tested in each of biological replicates). (***) P ≤ 0.001 were generated by student's t-test.",
    "ncbi_link": "PRR73: 4332464
prr73: 4332464"
  },
  {
    "caption": "E Null mutant of osprr73 in Nipponbare (NIP) background by genome editing displayed hypersensitivity to NaCl treatment. Scale bar, 5 cm. F Survival rate of NIP (wild type of CRISPR lines) and osprr73-C (C stands for CRISPR) plants in (E) after recovery 9 days. Data are presented as mean ± SD. n = 4 biological replicates, 24 plants for each biological replicate. (*) P ≤0.05 and (***) P ≤ 0.001 were generated by student's t-test.",
    "ncbi_link": "CRISPR: 
prr73: 4332464"
  },
  {
    "caption": "Quantification of  chlorophyll content of WT and  osprr73 mutants Data are presented as mean ± SD. n = 3, biological replicates, and asterisks represent significant difference among means by student's t-test with (*) P ≤0.05, (**) P ≤ 0.01, (***) P ≤ 0.001.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "Quantification of electrolyte leakage   of WT and  osprr73 mutants with or without 180 mM NaCl  treatment for 7 days. Data are presented as mean ± SD. n = 3, biological replicates, and asterisks represent significant difference among means by student's t-test with (*) P ≤0.05, (**) P ≤ 0.01, (***) P ≤ 0.001.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "A, B The Na+ and  K+  contents in the  shoots and roots  of DJ and osprr73 mutant plants with or without 180 mM NaCl treatment for 7 days. Na+ (A) and  K+ (B) contents were measured with ICP method. Data represent means ± SD, (n = 3, biological replicates). (**) P ≤ 0.001 and (*) P ≤ 0.001 indicate significant difference by student t-test. The abbreviation of n.s. stands for no significant. C Ratio of Na+ to  K+  was calculated with their respective content in (A) and (B). Data represent mean ± SD (n = 3, biological replicates). For each of biological replicates, 6 individual  plants were measured. The asterisk represents significant difference among means by student's t-test with (*) P ≤0.05, and n.s. indicates no significant.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "D Four-weeks old seedlings  of DJ and  osprr73  were treated with 90 mM Na2SO4 for 14 d (middle panel) and recovered for additional 7 days (right panel). Scale bar, 5 cm. E Statistical analysis of survival rates with  Na2SO4 treatment in (D). Data represent means ± SD. n = 3 biological replicates, 24 plants for each biological replicate. (***) P ≤ 0.001 indicates significant difference by student t-test. F The  seedlings  of DJ and osprr73 mutant were treated with 90 mM  MgCl2 for 14 days (middle panel) and recovered for 7 days (right panel). Scale bar, 5 cm. G Statistical analysis of survival rates  with MgCl2  treatment in (F). The survival rate  of DJ and osprr73 plants in  MgCl2 stress were calculated after recovery 7 days. Data represent means ± SD. n = 2 biological replicates, 24 plants of each replicate. H The  seedlings of DJ and osprr73 mutant were treated with 180 mM  mannitol for 36 days (middle panel) and recovered for 7 days (right panel). Scale bar, 5 cm. I The survival rate  of DJ and osprr73 plants in mannitol stress. Data represent means ± SD. n = 3 biological replicates, 24 plants of each replicate. The abbreviation of n.s. stands for no significant generated by student t-test.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "A, B The  expression level of  OsHKT2;1 and OsHKT1;5 in  osprr73 mutant and the wild control Dongjin (DJ) plants with or without salinity stress in multiple time points. DJ Data represent means ± SD. n = 3, technical replicates. The representative data is from at least two individual biological replicates. The asterisks represent significant difference among means by student's t-test with (*) P ≤0.05, (**) P ≤ 0.01 and (***) P ≤ 0.001.",
    "ncbi_link": "HKT1;5: 4327757
prr73: 4332464
HKT2;1: 4341971"
  },
  {
    "caption": "C Transient expression assay in the infiltrated leaves of  N. benthamiana  showing  OsPRR73 can repress OsHKT2;1 transcription. Left panel showing the bioluminescence  signal of   OsHKT2;1  and OsPRR73. Bioluminescence  of co-transformation of either  GFP or 35S: GFP-OsPRR73 (GFP-OsPRR73) with OsHKT2;1pro:  LUC in N. benthamiana. D Quantification of bioluminescence  intensity of OsHKT2;1pro: LUC shown in (C). Data represent means ± SD. n = 10. The asterisks indicate the significant difference by student's t-test with (***) P ≤ 0.001. At least two biological replicates were conducted with similar results.",
    "ncbi_link": "GFP: 
LUC: 
PRR73: 4332464
HKT2;1: 4341971"
  },
  {
    "caption": "E ChIP-qPCR assay showing the enriched DNA fragments including the S3 and S4 regions of OsHKT2;1 promoter by OsPRR73, compared to wild type DJ controls. The amplicon of  Ubiquitin was taken as a negative control. Two-week-old seedlings were harvested at ZT12. Data represent means ± SD (n =3, technical repeats). The experiments were performed at least two biological replicates with similar result. Top scheme indicates the locations of amplicons for ChIP  analysis. The asterisks represent significant difference among means by student's t-test with (**) P ≤ 0.01.",
    "ncbi_link": "HKT2;1: 4341971"
  },
  {
    "caption": "F EMSA  assay with the  OsPRR73  incubated with the probes designed for the S4 region of OsHKT2;1 promoter. Unlabelled probes were used as competitor with indicated folds. MBP alone was used as negative control. Arrowhead marks the shifted positive bands.",
    "ncbi_link": "HKT2;1: 4341971"
  },
  {
    "caption": "D N-terminus of OsPRR73 containing PR domain is required and sufficient for  interacting  with HDAC10. Upper panel shows the schematic illustration of full-length and the truncated OsPRR73 proteins. CoIP  was performed with  GFP-Trap beads, and  immunoprecipitants were detected by FLAG for HADC10  and GFP for truncated proteins of OsPRR73 respectively.",
    "ncbi_link": "PRR73: 4332464"
  },
  {
    "caption": "E, F Chromatin Immunoprecipitation-qPCR  (ChIP-qPCR) assay to detect the enriched promoter regions of OsHKT2;1 by using the H3K9ac (E) and H3 (F) antibodies. Two-week-old seedlings were harvested at ZT12. The locations of amplicons were described in Figure 4E. Data represent means ± SD. n = 3 technical replicates. The asterisk indicates the significant difference by student's t-test with (*) P ≤ 0.05. The experiments were repeated at least twice with similar result.",
    "ncbi_link": "HKT2;1: 4341971"
  },
  {
    "caption": "D The  oshkt2;1 seedling is more tolerant to the treatment of NaCl. The oshkt2;1 and NIP, its wild type, four-week-old seedlings  grown under NaCl conditions for 0 days (left panel), then were transferred to 200 mM NaCl  for 28 days (middle panel), and recovered for 7 days (right panel). Scale bar, 5 cm. E Statistical analysis of survival rate in (D). Data represent means ± SD. n = 3 biological replicates, 24 plants of each replicate. (*) P ≤ 0.05 was generated by student's t-test.",
    "ncbi_link": "hkt2;1: 4341971"
  },
  {
    "caption": "A Malondialdehyde  (MDA) content in leaves  of 14-d-old DJ and osprr73 plants  treated by 180 mM NaCl for 3 d and normal condition. Data represent means ± SD. n = 6, biological replicates. The asterisks indicate the significant difference (***) P ≤ 0.001 by student's t-test.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "B DAB staining showing the greater ROS accumulation in the leaves of osprr73 mutant treated by 180 mM  NaCl treatment for 3 days. Scale bar, 1 cm.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "C  H2O2  concentration was detected by using  H2DCFDA in the root tip of DJ and  osprr73 mutant  plants. Scale bar, 5 mm. -NaCl  and +NaCl  represented the untreated or treated plants  by NaCl respectively.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "D Quantitative analysis of H2O2 concentration in the root  of DJ and osprr73 mutant. Data represent means ± SD. n ≥ 6. The asterisks indicate the significant difference (***) P ≤ 0.001 by student's t-test.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": "E, F Measurement of SOD  (Superoxide dismutase) (E) and CAT (Catalase) (F) enzymes activity in  shoots  of DJ and osprr73 seedlings  with or without  NaCl stress. Data represent means ± SD. n = 3 technical replicates. Data are representative from two independent biological replicates with similar result. The asterisks indicate the significant difference (*) P ≤ 0.05 by student's t-test.",
    "ncbi_link": "prr73: 4332464"
  },
  {
    "caption": " I: PPARγ mRNA expression is induced following 20nM mithramycin treatment as measured by qPCR fold-change relative to GAPDH (2ddCT). **, P = 0.002, ****, P = 0.0001. Data represents mean with standard deviation derived from three independent experiments. P-values were determined by one-way ANOVA using Dunnet test for multiple comparisons. ",
    "ncbi_link": "GAPDH: 2597
PPARγ: 5468"
  },
  {
    "caption": "C: SMARCC1 and SMARCE1 mRNA expression does not change following 100nM mithramycin treatment as measured by qPCR fold-change relative to GAPDH (2ddCT). Data represents mean with standard deviation derived from three independent experiments.",
    "ncbi_link": "GAPDH: 2597
SMARCC1: 6599
SMARCE1: 6605"
  },
  {
    "caption": " E: Loss of SWI/SNF occupancy at defined loci in the genome as measure by chromatin immunoprecipitation qPCR (ChIP-qPCR) at previously described SWI/SNF target genes, MYT1 (8-hour, P=0.0001; 18-hour P=0.0001) and CCND1 (8-hour, P=0.0001; 18-hour P=0.0001). ChIP quantitation is percent input (ng of immunoprecipitated DNA/input DNA *100) determined by absolute quantitation of sheared chromatin relative to a standard curve. Data represents mean with standard deviation derived from three independent experiments. P-values were determined by one-way ANOVA using Dunnet test for multiple comparisons. ",
    "ncbi_link": "CCND1: 595
MYT1: 4661"
  },
  {
    "caption": " F: Chromatin immunoprecipitation qPCR (ChIP-qPCR) of H3K27me3 at MYT1 (8-hour, P= 0.0001; 18-hour P=0.0001) and CCND1 (8-hour, P=0.02; 18-hour P=0.0001). H3K27me3 occupancy is increased in a time-dependent manner. ChIP quantitation is percent input (ng of immunoprecipitated DNA/input DNA *100) determined by absolute quantitation of sheared chromatin relative to a standard curve. Data represents mean with standard deviation derived from three independent experiments. P-values were determined by one-way ANOVA using Dunnet test for multiple comparisons. ",
    "ncbi_link": "CCND1: 595
MYT1: 4661"
  },
  {
    "caption": " Western blot showing concentration-dependent increase in H3K27me3 following exposure to 100nM, 50nM, 25nM mithramycin for 18h in G401 cells relative to loading control (H3). Re-expression of SMARCB1 following doxycycline treatment inhibits the mithramycin-dependent effects on H3K27me3 amplification ",
    "ncbi_link": "SMARCB1: 6598"
  },
  {
    "caption": " A, B: Mithramycin displaces BRD9 and SMARCE1 SWI/SNF subunits from chromatin in a time-dependent manner in G401 (A) but only BRD9 with SMARCB1 re-expression in G401 (B) cells. Western blot analysis showing whole cell lysate (Total), cytoplasmic soluble (CS), nuclear soluble (NS), and chromatin bound (Chr) fractions collected after exposure to solvent (S) or 100nM mithramycin for 8 or 18h and probed for the SWI/SNF subunits (BRD9, SMARCB1 or SMARCE1) or H3 (chromatin fraction control) and GAPDH (soluble fraction control). ",
    "ncbi_link": "SMARCB1: 6598"
  },
  {
    "caption": " E: Suppression of EZH2 expression and activity antagonizes mithramycin activity in BT12 rhabdoid tumor cells. Data represents dose response curves of mithramycin in BT12 cells following a 48h exposure in the presence of siRNA silencing of the PRC2 subunit EZH2 or treatment with the EZH2 inhibitor EPZ-6438 relative to mithramycin alone (media) or a non-targeting siRNA (siNeg). Data represents mean with standard deviation derived from three independent experiments. ",
    "ncbi_link": "EZH2: 2146"
  },
  {
    "caption": " F: Suppression of SMARCB1 sensitizes U2OS osteosarcoma cells (wild type SWI/SNF) to mithramycin. Data represents dose response curves of mithramycin in BT12 cells following a 48h exposure in the presence of siRNA silencing of the SWI/SNF subunit SMARCB1 relative to a non-targeting siRNA (siNeg). Data represents mean with standard deviation derived from three independent experiments. ",
    "ncbi_link": "SMARCB1: 6598"
  },
  {
    "caption": " G. Western blot showing concentration-dependent increase in H3K27me3 following exposure to 100nM, 50nM, 25nM mithramycin for 18h in SMARCB1- silenced U2OS cells relative to loading control (H3). Knockdown of SMARCB1 following siRNA suppression triggers mithramycin-dependent H3K27me3 amplification, while siNegative (control) does not have an effect on H3K27me3 following mithramycin exposure. ",
    "ncbi_link": "SMARCB1: 6598"
  },
  {
    "caption": " E: IGV tracks of rhabdoid tumor genes previously identified to be occupied by non-canonical SWI/SNF (Michel et al., 2018). ID3 and JUND3 decrease in H3K27ac occupancy and chromatin accessibility following exposure to mithramycin for 8-hours or 18-hours. ",
    "ncbi_link": "ID3: 3399
JUND3: 3727"
  },
  {
    "caption": " F: IGV tracks of rhabdoid tumor genes previously identified to gain H3K27me3 upon SWI/SNF loss (Erkek et al., 2019). CDK6 and CDK2 decrease in H3K27ac occupancy and chromatin accessibility following exposure to 8-hours and 18-hours mithramycin treatment. ",
    "ncbi_link": "CDK2: 1017
CDK6: 1021"
  },
  {
    "caption": " G: IGV tracks of genes identified to have an increase in accessibility, H3K27ac and gene expression following mithramycin exposure. BMP1 and ADIPOR1 play crucial roles in bone and adipogenic differentiation, respectively. ",
    "ncbi_link": "ADIPOR1: 51094
BMP1: 649"
  },
  {
    "caption": "HUVECs transfected with control or CEP41 siRNAs were scratched (0 h) to induce wounding and then incubated for 12 h to allow wound closure. The wound margins were observed every 4 h in the CEP41#1 and #2 siRNA-transfected cells and compared to those of control cells. Representative images of cells subjected to the wound closure assay in (A). Scale bars, 600 μm. Quantification of the extent of wound closure in (B) presented graphically by measuring the distance between the dotted lines at each time point.",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Tubulogenesis of control and CEP41-knockdown cells for 18 h was compared via an in vitro angiogenesis assay. Scale bars, 600 μm. Quantification of tube node numbers in (F) and tube length in (G) from each field of view using the ImageJ angiogenesis analyzer at the indicated time points. The graph compares the relative length of control cells and CEP41-knockdown cells. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition.",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Blood vessels were observed in MOs (control, cep41 AUG (2.5 ng), or cep41 SB (2 ng))-injected or cep41-mutated Tg(kdrl:eGFP) zebrafish at 40 hours post-fertilization (hpf) by fluorescent microscopy. Asterisks and arrowheads indicate impaired ISVs and DLAVs, respectively. The representative images for analysis of ISV lumen diameter are indicated by dotted rectangles. A, anterior; P, posterior; DLAV, dorsal longitudinal anastomotic vessel; ISV, intersegmental vessel. Scale bars, 100 μm. Quantification of ISV lumen diameter in (B), the numbers of defective ISVs in (C), the numbers of embryos with aberrant DLAVs in (D), and the numbers of ruptured DLAVs in (E) from data observed in equivalent fields of view (within eight somites). The severity of blood vessel defects in cep41-deficient zebrafish: B (narrowed ISVs) < C (shorten, fused, and missing ISVs) < D and E (ruptured DLAVs). Data are shown as mean ± SD of three independent experiments with ≥ 20 embryos per condition.",
    "ncbi_link": "eGFP: 
cep41: 431741
kdrl: 796537"
  },
  {
    "caption": "Control or CEP41 siRNA-transfected HUVECs were immunostained with Ac-Tub- or GT335-specific antibodies in (A). The rectangles indicate the representative cells from each immunostaining experiment presented as magnified images in the right panels. Scale bars, 20 μm. Quantification of the ciliated cell numbers in the images in (A) from the results of three independent experiments with ≥ 200 cells per condition (mean ± SD) in (B).",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Wild-type and cep41-deficient Tg(kdrl:eGFP) zebrafish embryos were fixed for immunostaining with Ac-Tub- or GT335-specific antibodies at 28 hpf in (C). The rectangles indicate the arterial cilia (AC) and venous cilia (VC) in zebrafish endothelial cells (EC). Magnified representative images are displayed in the right panels. Scale bars, 40 μm. Quantification of the labeled cilia observed in equivalent fields of view are presented graphically in (D). Data are shown as median of three independent experiments (n ≥ 20 embryos per condition).",
    "ncbi_link": "eGFP: 
cep41: 431741
kdrl: 796537"
  },
  {
    "caption": "HUVECs transfected with CCP5 and/or CEP41 siRNAs were scratched and incubated to evaluate wound closure. The extent of wound closure in co-transfected cells with CCP5 and CEP41 siRNAs was compared with that in control or CEP41 siRNA-transfected cells at the indicated time points (A). Scale bars, 600 μm. Quantification of the extent of wound closure in (A) is presented graphically by measuring the distance between the dotted lines at each time point in (B). Data are shown as mean ± SD of three independent experiments (n ≥ 3 scratches per experimental condition).",
    "ncbi_link": "CCP5: 60509
CEP41: 95681"
  },
  {
    "caption": "The indicated siRNA-transfected HUVECs were subjected to in vitro angiogenesis assays. Tubulogenesis of HUVECs depleted for CEP41 and CCP5 was compared to that of control, CEP41 single-knockdown, or CCP5 single-knockdown cells (C). Scale bars, 600 μm. Quantification of tube node number in (D) and tube length in (E) from data examined within equivalent fields of view at the indicated time points using the ImageJ angiogenesis analyzer. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition.",
    "ncbi_link": "CCP5: 60509
CEP41: 95681"
  },
  {
    "caption": "The blood vessels in the trunks of cep41-mutant/morphant zebrafish were compared to those of zebrafish co-injected with ccp5 MOs (2 ng) at 40 hpf in (F). Asterisks and arrowheads indicate impaired ISVs and DLAVs, respectively. A, anterior; P, posterior. Scale bars, 100 μm. Quantification of the number of defective ISVs and DLAVs from data observed in equivalent fields of view (within eight somites). Data are median of three independent experiments with ≥ 20 embryos per condition.",
    "ncbi_link": "ccp5: 445479
cep41: 431741"
  },
  {
    "caption": "HUVECs co-transfected with CEP41 and CCP5 siRNAs were immunostained with ARL13b- and GT335-specific antibodies. The staining results were compared to those of control, single CEP41, or CCP5 siRNA-transfected cells. Representative images indicated with rectangles appear in magnified images in the lower panels. Scale bars, 20 μm. Quantification of relative intensity of GT335/ARL13b signals in the cilia ciliary length (J) in images (H) are the result of three independent experiments with ≥ 200 cells per condition (median). **",
    "ncbi_link": "CCP5: 60509
CEP41: 95681"
  },
  {
    "caption": "Control or CEP41 siRNA-transfected HUVECs cultivated under either static or shear stress states and examined in a wound healing assay in (A). Scale bars, 600 μm. Quantification of the extent of wound closure in (A) displayed graphically by measuring the distance between the lines at the indicated time points in (B). Data are presented as mean ± SD of three independent experiments (n ≥ 3 scratches per experimental condition). Statistical significance was determined using the two-way ANOVA followed by Tukey's post hoc test (***P < 0.01, ns: non-significant).",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Control or CEP41-deficient HUVECs cultivated under laminar shear stress and immunostained with ARL13b-specific antibodies to measure deciliation. Representative images are indicated by rectangles with numbers and shown in magnified images in the right panels. The resulting data were compared to those of cells under static conditions in (F). Scale bars, 20 μm. Quantification of ARL13b-positive ciliary cells (G) and of relative intensity of GT335/ARL13b signals in the cilia (H) in images (F) is the results of three independent experiments with ≥ 200 cells per condition (mean ± SD (G), median (H)). *",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Control, CEP41-, or CCP5-depleted hTERT-RPE1 cells cultured under serum starvation for 48 h and fixed at 18 h after serum retrieval for immunostaining with both ARL13b- and GT335-specific antibodies in (I). Images of the results 18 h after serum addition. Representative cells are indicated by rectangles. Scale bars, 20 μm. Quantification of ARL13b-positive ciliated cells (J) and relative intensity of GT335/ARL13b signals in the cilia (K) under either serum starvation or serum retrieval (18 h) conditions are the results of three independent experiments with ≥ 200 cells per condition (mean ± SD (J), median (K)).",
    "ncbi_link": "CCP5: 60509
CEP41: 95681"
  },
  {
    "caption": "VEGFA (A) and VEGFR2 (B) mRNA levels quantified by qRT-PCR in control or CEP41-knockdown HUVECs under static or shear stress conditions. The expression of GAPDH was quantified for the normalization of the qRT-PCR results. Data are shown as mean ± SD of three independent experiments. Statistical significance was determined with the Brown-Forsythe ANOVA followed by Dunnett's T3 post hoc test (**P < 0.01, ***P < 0.001, ns: non-significant).",
    "ncbi_link": "GAPDH: 
CEP41: 95681
VEGFR2: 3791
VEGFA: 7422"
  },
  {
    "caption": "The mRNA levels of zebrafish vegfa (E) and vegfr2 (F) were quantified by qRT-PCR in eGFP-positive ECs of control- or cep41-MO-injected Tg(kdrl:eGFP) zebrafish at 18 hpf (low shear stress) and 26 hpf (high shear stress). The expression of vegfa and vegfr2 was quantified in neuronal cells from control MO-injected zebrafish for comparisons with that of ECs. The expression of zebrafish β-actin was quantified for the normalization of those qRT-PCR results. Data are shown as mean ± SD of three independent experiments. Statistical significance was determined using the one-way ANOVA followed by Tukey's post hoc test (***P < 0.001, ns: non-significant).",
    "ncbi_link": "β-actin: 
eGFP: 
cep41: 431741
vegfr2: 554230
kdrl: 796537
vegfa: 30682"
  },
  {
    "caption": "Tg(kdrl:eGFP) zebrafish were injected with control- or cep41-MOs and subjected to immunostaining with phospho-AURKA-specific antibodies (red) and DAPI at 26 hpf. The insets indicate the representative area from each immunostaining experiment and the red dots indicate EC aurka activation. Scale bars, 40 μm. Quantification of the phospho-aurka-positive ECs (H) in equivalent fields of view for each MO-injected zebrafish in images in (G) are the result of three independent experiments with ≥ 10 embryos per condition. The top and bottom whiskers represent the maximum and minimum values, respectively. **P < 0.01 (Unpaired Student's t-test with Welch's correction).",
    "ncbi_link": "eGFP: 
cep41: 431741
kdrl: 796537"
  },
  {
    "caption": "CEP41-depleted hTERT-RPE1 cells were transfected with vectors encoding nothing (MOCK), AURKA-T288D, or AURKA-K162R and then immunostained with ARL13b-specific antibodies after serum starvation or serum retrieval. Images were taken from the results of staining done 18 h after serum retrieval. Rectangles indicate the representative cells that appear in the magnified images in the right panels. Scale bars, 20 μm. A quantification of ARL13b-labeled ciliated cells under the indicated conditions in (J). These are the results of three independent experiments with ≥ 200 cells per condition (mean ± SD). *P < 0.05, ***P < 0.01, ns: non-significant (Two-way ANOVA with Tukey's post hoc test).",
    "ncbi_link": "AURKA: 6790
CEP41: 95681"
  },
  {
    "caption": "Control and CEP41-deficient HUVECs were transfected with expression vectors encoding nothing (MOCK), AURKA, AURKA-T288D, or AURKA-K162R and subjected to an in vitro angiogenesis assay for 18 h under static (K, L) or shear stress (M, N) states. Quantification of tube node number in (K, M) and tube length in (L, N) from data examined within equivalent fields of view at each time point using the ImageJ angiogenesis analyzer. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition. Statistical significance was determined using the two-way ANOVA followed by Tukey's post hoc test (*P < 0.05, **P < 0.01, ***P < 0.001, ns: non-significant).",
    "ncbi_link": "AURKA: 6790
CEP41: 95681"
  },
  {
    "caption": "The control or CEP41 siRNA-transfected HUVECs were cultivated under hypoxia (1% O2) and their whole cell lysates were used for immunoblot assays of CEP41, phospho-AURKA, and AURKA. The resulting data were also compared to those of normoxic cells. Protein levels were normalized against β-ACTIN in the same blots.",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "VEGFA (B) and VEGFR2 (C) mRNA levels were measured by qRT-PCR using cDNA from normoxic and hypoxic controls or CEP41-depleted cells. The expression of GAPDH was quantified for the normalization of those qRT-PCR results.",
    "ncbi_link": "GAPDH: 
CEP41: 95681
VEGFR2: 3791
VEGFA: 7422"
  },
  {
    "caption": "Tg(kdrl:eGFP) zebrafish were injected with control- or cep41-MOs and then incubated under hypoxia at 28 hpf (a stage of high shear stress) for 2 h. They were subjected to immunostaining with phospho-AURKA-specific antibodies (red) and DAPI at 30 hpf. The insets indicate the representative areas from each immunostaining and red dots indicate activated aurka within ECs. Scale bars, 40 μm. Quantification of phospho-aurka-positive ECs (E) in equivalent fields of view for each MO-injected zebrafish in (D) are the result of three independent experiments with ≥ 20 embryos per condition. The top and bottom whiskers represent the maximum and minimum values, respectively. *P < 0.05 (Unpaired Student's t-test).",
    "ncbi_link": "eGFP: 
cep41: 431741
kdrl: 796537"
  },
  {
    "caption": "Zebrafish vegfa mRNA levels were quantified by qRT-PCR in eGFP-positive ECs of control- or cep41-MO-injected Tg(kdrl:eGFP) zebrafish subjected to either normoxia or hypoxia at 30 hpf. The expression of zebrafish β-actin was quantified for the normalization of these qRT-PCR results.",
    "ncbi_link": "β-actin: 
eGFP: 
cep41: 431741
kdrl: 796537
vegfa: 30682"
  },
  {
    "caption": "vegfr2 (G) mRNA levels were quantified by qRT-PCR in eGFP-positive ECs of control- or cep41-MO-injected Tg(kdrl:eGFP) zebrafish subjected to either normoxia or hypoxia at 30 hpf. The expression of zebrafish β-actin was quantified for the normalization of these qRT-PCR results.",
    "ncbi_link": "β-actin: 
eGFP: 
cep41: 431741
vegfr2: 554230
kdrl: 796537"
  },
  {
    "caption": "Control and CEP41-deficient HUVECs, transfected with expression vectors encoding nothing (MOCK), AURKA, AURKA-T288D, HIF1α, or HIF1α with CEP41 were cultivated under hypoxia and subjected to an in vitro angiogenesis assay for 18 h. Scale bars, 400 μm.",
    "ncbi_link": "AURKA: 6790
CEP41: 95681
HIF1α: 3091"
  },
  {
    "caption": "Control and CEP41-deficient HUVECs, transfected with expression vectors encoding nothing (MOCK), AURKA, AURKA-T288D, HIF1α, or HIF1α with CEP41 were cultivated under hypoxia and subjected to an in vitro angiogenesis assay for 18 h. Scale bars, 400 μm. Quantification of tube node number in (I) and tube length in (J) from data examined within equivalent fields of view at each time point using the ImageJ angiogenesis analyzer. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition.",
    "ncbi_link": "AURKA: 6790
CEP41: 95681
HIF1α: 3091"
  },
  {
    "caption": "HUVECs transfected with control or CEP41 siRNAs were cultivated under hypoxia and their whole cell lysates were used for immunoblot assays of HIF1α. The HIF1α expression of hypoxic cells was compared to that of normoxic cells and the protein levels were normalized against β-ACTIN in the same blot.",
    "ncbi_link": "CEP41: 95681"
  },
  {
    "caption": "Co-immunoprecipitation assays using HIF1α-, and CEP41-specific antibodies were performed in HEK 293T cells expressing GFP-CEP41 under normoxia or hypoxia. An IP using IgG-specific antibodies was performed as a negative control. NOR, normoxia; HYP, hypoxia.",
    "ncbi_link": "GFP: 
CEP41: 95681"
  },
  {
    "caption": "The CEP41-depleted HUVECs were transfected with expression vectors encoding nothing (MOCK), CEP41, or HIF1α and cultivated under hypoxia. Whole cell lysates were used for immunoblot assays for phospho-AURKA and AURKA, and the resulting data were compared to those of normoxic and hypoxic control cells. Protein levels were normalized against β-ACTIN in the same blots. NOR, normoxia; HYP, hypoxia.",
    "ncbi_link": "CEP41: 95681
HIF1α: 3091"
  },
  {
    "caption": "The CEP41-deficient HUVECs were transfected with expression vectors encoding nothing (MOCK), CEP41, HIF1α, or HIF1α with CEP41 and exposed to hypoxia. VEGFA (E) and VEGFR2 (F) mRNA levels were analyzed by qRT-PCR using cDNA from transfected cells. Data are shown as mean ± SD of three independent experiments. Statistical significance was determined using the one-way ANOVA followed by Tukey's post hoc test (***P < 0.001, ns: non-significant). NOR, normoxia; HYP, hypoxia.",
    "ncbi_link": "CEP41: 95681
HIF1α: 3091
VEGFR2: 3791
VEGFA: 7422"
  },
  {
    "caption": "Control or CEP41-depleted HUVECs were transfected with expression vectors encoding nothing (MOCK) or HIF1α and treated with MG132 or not, and then the cells were cultivated under hypoxia. Whole cell lysates were used for immunoblot assays for HIF1α, phospho-AURKA, and AURKA, and the protein levels were normalized against β-ACTIN in the same blots. NOR, normoxia; HYP, hypoxia.",
    "ncbi_link": "CEP41: 95681
HIF1α: 3091"
  },
  {
    "caption": "Quantification of tube node number in (H) and tube length in (I) from in vitro angiogenesis assays with HIF1α #1 or #2 siRNAs-transfected HUVECs overexpressing nothing (MOCK) or CEP41 under hypoxia. Data are shown as mean ± SD of five independent experiments with ≥ 5 tubulogenesis regions per condition.",
    "ncbi_link": "CEP41: 95681
HIF1α: 3091"
  },
  {
    "caption": "VEGFA (J) and VEGFR2 (K) mRNA levels were analyzed by qRT-PCR using cDNA from hypoxic HIF1α-depleted HUVECs transfected with control or CEP41 expression vectors. The results were compared to those of control and normoxic HIF1α-depleted cells. Data are shown as mean ± SD of three independent experiments.",
    "ncbi_link": "CEP41: 95681
HIF1α: 3091
VEGFR2: 3791
VEGFA: 7422"
  },
  {
    "caption": "Wip1 represses the gene responses induced by Nodal or BMP signaling in animal caps as analyzed by RT-PCR. ODC serves as a loading control. -RT, control in the absence of reverse transcriptase. WE, whole embryo. Co AC, uninjected control animal caps. (-), no injection of wild-type (wt) Wip1 or Wip1(D277A) mRNA. The amount of mRNA injected: wt Wip1 (1 ng), Wip1(D277A) (1 ng), Xnr1 (50 pg)",
    "ncbi_link": "ODC: 
Nodal: 378543
Xnr1: 378543
Wip1: 443988///380383"
  },
  {
    "caption": "Wip1 represses the gene responses induced by Nodal or BMP signaling in animal caps as analyzed by RT-PCR. ODC serves as a loading control. -RT, control in the absence of reverse transcriptase. WE, whole embryo. Co AC, uninjected control animal caps. (-), no injection of wild-type (wt) Wip1 or Wip1(D277A) mRNA. The amount of mRNA injected: wt Wip1 (1 ng), Wip1(D277A) (1 ng), BMP4 (100 pg).",
    "ncbi_link": "ODC: 
BMP4: 397874///399322
Wip1: 443988///380383"
  },
  {
    "caption": "Wip1 represses the gene responses induced by Nodal or BMP signaling in animal caps as analyzed by RT-PCR. ODC serves as a loading control. -RT, control in the absence of reverse transcriptase. WE, whole embryo. Co AC, uninjected control animal caps. (-), no injection of wild-type (wt) Wip1 or Wip1(D277A) mRNA. The amount of mRNA injected: wt Wip1 (1 ng), Wip1(D277A) (1 ng)",
    "ncbi_link": "ODC: 
Wip1: 443988///380383"
  },
  {
    "caption": "(D wt Wip1, but not Wip1(D277A), down-regulates the activity of Activin- or BMP-responsive promoters in HEK293T cells. FAST1, were co-transfected as indicated for efficient activation of the promoters. Data are expressed as the mean ± SEM (n=3 biological replicates). *P<0.05 by unpaired Student's t-test.",
    "ncbi_link": "Activin: 91
FAST1: 398070
Wip1: 443988///380383"
  },
  {
    "caption": "E) wt Wip1, but not Wip1(D277A), down-regulates the activity of Activin- or BMP-responsive promoters in HEK293T cells. Smad1 and Smad4 were co-transfected as indicated for efficient activation of the promoters. Data are expressed as the mean ± SEM (n=3 biological replicates). *P<0.05 by unpaired Student's t-test.",
    "ncbi_link": "Wip1: 443988///380383
Smad1: 399457///379664
Smad4: 4089"
  },
  {
    "caption": "(F-Q) Dorsal (F-N) or ventral (O-Q) injection of wt Wip1 abrogates the in vivo expression of mesodermal markers at stage 10.25 as analyzed by in situ hybridization. Embryos are shown in vegetal views with dorsal to the top. Arrowheads denote the absence of expression of mesodermal markers in the injected region of embryos. Control, an embryo injected with LacZ only. The amount of mRNA injected: wt Wip1 (1 ng), Wip1(D277A) (1 ng) and LacZ (100 pg). Scale bar, 150 μm.",
    "ncbi_link": "LacZ: 945006
Wip1: 443988///380383"
  },
  {
    "caption": "(A, Nodal-induced gene responses are enhanced further in the absence of Wip1 as analyzed by RT-PCR. Animal caps ere treated with -), no injection of Co MO, Wip1 MO and/or Wip1 mRNA. The dose of reagent injected: Xnr1 (5 pg), Co MO (60 ng), Wip1 MO (60 ng) and Wip1 (1 ng).",
    "ncbi_link": "Xnr1: 378543
Nodal: 378543
Wip1: 380383///443988"
  },
  {
    "caption": "B) Activin/Nodal-induced gene responses are enhanced further in the absence of Wip1 as analyzed by RT-PCR. Animal caps in (B) were treated with Activin protein (5 ng/ml). (-), no injection of Co MO, Wip1 MO and/or Wip1 mRNA. The dose of reagent injected: Co MO (60 ng), Wip1 MO (60 ng) and Wip1 (1 ng).",
    "ncbi_link": "Wip1: 380383///443988"
  },
  {
    "caption": "(C) Knockdown of Wip1 up-regulates the activity of Activin/Nodal-responsive promoter. HEK293T cells transfected with Co siRNA (50 nM) or Wip1 siRNA (50 nM) were stimulated with Activin protein (10 ng/ml) for 10 h and then subjected to luciferase assays. Data are expressed as the mean ± SEM (n=3 biological replicates). ***P<0.001 by unpaired Student's t-test.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "Depletion of Wip1 promotes epidermal differentiation at the expense of neural fate. (-), no injection of Noggin mRNA. The amount of MO and mRNA injected: Co MO (60 ng), Wip1 MO (60 ng for D, G and J; 30 ng for F and I) and Noggin (5, 10, 20 pg). Scale bar, 150 μm.",
    "ncbi_link": "Noggin: 108704141///373646
Wip1: 443988///380383"
  },
  {
    "caption": "Depletion of Wip1 promotes epidermal differentiation at the expense of neural fate. Embryos in (E-J) are shown in dorsal views with anterior to the top. The amount of MO and mRNA injected: Co MO (60 ng), Wip1 MO (60 ng for D, G and J; 30 ng for F and I) and Noggin (5, 10, 20 pg). Scale bar, 150 μm.",
    "ncbi_link": "Noggin: 108704141///373646
Wip1: 443988///380383"
  },
  {
    "caption": "(K, Activin induction of p21 is up-regulated upon Wip1 knockdown. HEK293T cells were transfected with Co siRNA or Wip1 siRNA and 48 h after siRNA transfection, were stimulated with Activin (10 ng/ml) for 3 to 12 h as indicated t=0 in (K) is 48 h after siRNA transfection. P-Smad2 serves as an indicator of active Activin/Nodal signaling. Arrows ndicate non-specific bands.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "L) TGF-β induction of p21 is up-regulated upon Wip1 knockdown. HEK293T cells were transfected with Co siRNA or Wip1 siRNA and 48 h after siRNA transfection, were stimulated with increasing concentration of TGF-β1 (10, 20 ng/ml) for 3 h.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "(A, Effects of the gain- or loss-of-function of Wip1 on TGF-β-induced growth arrest. HEK293T cells were transfected or not with wt Wip1, Wip1(D277A), as indicated and subjected to CCK-8 assays before (0 h) and after stimulation with TGF-β1 (40 ng/ml) (24 h). Data are presented as the mean ± SEM (n=3 biological replicates). *P<0.05, **P<0.01, ***P<0.001 by unpaired Student's t-test. n.s., not significant.",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "B) Effects of the gain- or loss-of-function of Wip1 on TGF-β-induced growth arrest. HEK293T cells were transfected or not with Co siRNA or Wip1 siRNA as indicated and subjected to CCK-8 assays before (0 h) and after stimulation with TGF-β1 (40 ng/ml) (24 h). Data are presented as the mean ± SEM (n=3 biological replicates). *P<0.05, **P<0.01, ***P<0.001 by unpaired Student's t-test. n.s., not significant.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "Depletion of Wip1 augments TGF-β-induced migration and invasion of MDA-MB231 breast cancer cells. MDA-MB231 cells transfected with Co siRNA or Wip1 siRNA were scratched with a 20-μL pipette tip and then incubated in the absence or presence of TGF-β1 for the indicated times (C, D)",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "Depletion of Wip1 augments TGF-β-induced migration and invasion of MDA-MB231 breast cancer cells. MDA-MB231 cells transfected with Co siRNA or Wip1 siRNA were subjected to transwell assay with or without TGF-β1 for 20 h (E, F).",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "(A-D) Knockdown of Wip1 expands the expression of dorsal mesodermal markers. Embryos injected dorsally with Co MO (40 ng) or Wip1 MO (40 ng) were subjected to in situ hybridization at stage 10.25. Embryos are shown in dorso-vegetal views with dorsal to the top. Scale bar, 150 μm.",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "(E-I) Morphological phenotypes of Wip1 morphants. Embryos were injected radially in the marginal zone with Co MO (80 ng), Wip1 MO (80 ng), wt Wip1 (1 ng) and Wip1(D277A) mRNA as indicated and cultured to tadpole stages. Embryos are shown in lateral views with anterior to the left. Un Co, uninjected control. Scale bar, 1 mm. (J) Quantification of the phenotypes shown in (E-I). Severe defects include microcephaly, shortened and kinked body axis, and no eye. Mild defects indicate normal body axis with malformed eyes. ",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "(E) Wip1 interferes with the ability of Smad4 to bind to Smad2. HEK293T cells co-transfected with the indicated constructs were treated or not with TGF-β1 for 1 h and then harvested. An arrow denotes Myc-tagged Wip1 protein.",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "(F) Wip1 has a negative effect on nuclear accumulation of Smad4. HEK293T cells were transfected with Co siRNA or Wip1 siRNA, treated with TGF-β1 (40 ng/ml, 1 h) 48 h after siRNA transfection and subjected to nuclear/cytoplasmic fractionation and western blotting analysis. β-tubulin and lamin A/C serve as cytoplasmic and nuclear markers, respectively. C, cytoplasm; N, nucleus. The experiment was repeated two times with similar results. (G) Quantification of the levels of nuclear Smad4 normalized to those of cytoplasmic Smad4 shown in (F). ",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "(A) Overexpression of Wip1 down-regulates Smad4 phosphorylation at Thr277. MOCK- or Flag-Wip1-transfected HEK293T cells were treated with 1 h pulse of FGF2 (10 ng/ml), followed by addition of U0126 (40 μM) and harvesting for western blotting at the indicated times. - FGF2, no treatment with FGF2.",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "(B) Time course of Smad4 phosphorylation at Thr277 induced by FGF2 in control and Wip1-depleted HEK293T cells, showing that knockdown of Wip1 up-regulates Smad4 phosphorylation at the MAPK site. A bracket denotes phospho-Smad4.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "(C) Wip1 directly dephosphorylates Smad4 at Thr277 as assayed by in vitro phosphatase assay. Myc-tagged Smad4 was expressed in HEK293T cells, which were then treated or not with FGF2 (40 ng/ml, 2 h), and the Myc-Smad4 was immunoprecipitated using anti-Myc antibody and subsequently incubated with or without recombinant human Wip1 protein (0.5 μg) in the absence or presence of Mg2+ as indicated.",
    "ncbi_link": "Myc: 
Smad4: 4089"
  },
  {
    "caption": "(D) FGF-induced destabilization of Smad4 is enhanced further in Wip1-depleted animal cap cells as analyzed by western blotting. The amount of reagent injected: Myc-Smad4 (400 pg), FGF8 (100 pg), Wnt8 (400 pg), Co MO (60 ng) and Wip1 MO (60 ng).",
    "ncbi_link": "FGF8: 108697431///399183
Wip1: 443988///380383
Smad4: 4089
Wnt8: 397970"
  },
  {
    "caption": "(E) Polyubiquitination of wt Smad4 is promoted in Wip1-silenced cells. HEK293T cells were transfected with the indicated combinations of Flag-ubiquitin, Co siRNA, Wip1 siRNA, Myc-Smad4 and Myc-Smad4(T277A) and then treated with FGF2 (10 ng/ml, 4 h) in the presence of the proteasome inhibitor MG132, and Myc-Smad4 and its phosphorylation-resistant mutant were immunoprecipitated with anti-Myc antibody. Ubiquitin-conjugated Smad4 (Smad4-Ubn) was detected by western blotting with anti-Flag antibody.",
    "ncbi_link": "Flag: 
Myc: 
ubiquitin: 
Wip1: 8493
Smad4: 4089"
  },
  {
    "caption": "(F) Wip1 prolongs the half-life of Smad4. HEK293T cells were transfected with Co siRNA or Wip1 siRNA and then treated with FGF2 along with cycloheximide (CHX, 100 ng/ml) for the indicated times and harvested for western blotting. An arrow indicates non-specific bands.",
    "ncbi_link": "Wip1: 8493"
  },
  {
    "caption": "(A-J) Embryos injected dorsally with wt Wip1 (1 ng), wt Smad4 (1 ng), Smad4(T277A) (1 ng) and Smad4 (T277E) (1 ng) as denoted were subjected to in situ hybridization against Chordin or Xbra at stage 10.25. Control, control embryo injected with LacZ mRNA only. Scale bar, 150 μm. (K) Quantification of the results from in situ hybridization analysis in (A-J). ",
    "ncbi_link": "LacZ: 945006
Wip1: 443988///380383
Smad4: 4089"
  },
  {
    "caption": "(L) Wip1-mediated neural induction is inhibited by Smad4 with a phosphorylatable or phospho-mimetic amino acid at the MAPK site. (-), no co-injection of wt or mutated Smad4.",
    "ncbi_link": "Wip1: 443988///380383
Smad4: 4089"
  },
  {
    "caption": "(M) MDA-MB231 and MDA-MB468 cells were transfected with wt Wip1 alone or with wt Smad4 or Smad4(T277A) and then subjected to CCK-8 assays to measure cell growth. Data are presented as the mean ± SEM (n=3 biological replicates). *P<0.05 by unpaired Student's t-test.",
    "ncbi_link": "Wip1: 443988///380383
Smad4: 4089"
  },
  {
    "caption": "(N) Anchorage-independent colony-formation assays were performed in MDA-MB231 and MDA-MB468 cells transfected with Wip1 or negative control constructs. Scale bar, 100 μm. (O) Quantification of the assays shown in (N). The number of colonies larger than 50 μm in diameter was scored. Data are expressed as the mean ± SEM (n=3 biological replicates). *P<0.05 by unpaired Student's t-test. ",
    "ncbi_link": "Wip1: 443988///380383"
  },
  {
    "caption": "(F) Graph reporting the volume of blood loss (µL) over 30 minutes following the tail clip. WT: wild-type littermates of F9-/- mice. The grey area represents the range of blood loss of F9-/- mice that received AAV-vectors expressing human FIX. Data are presented as mean±SD (n=3-4/group), and were analyzed in a 1-way ANOVA with Tukey's correction for multiple comparisons. **p<0.01 Boxes represent 25%-75% quartiles, with the line indicating the median. Whiskers span min to max.",
    "ncbi_link": "F9-/-: 14071
FIX: 2158"
  },
  {
    "caption": " (B) Western blotting of WT and Drp1-KO MEFs with or without FCCP treatment (30 min) using the indicated antibodies. ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (B) Western blotting of WT MEFs, Drp1-KO MEFs, and Drp1-KO MEFs carrying Drp1, all of which express L2-HA, using the indicated antibodies. The expression of L2-HA was induced for 16 h (0.1 µg/ml doxycycline). The asterisk indicates non-specific bands of anti-Oma1 antibodies. ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (E) WT and Drp1-KO MEFs, both of which express L2-HA, were transduced with lentiviruses carrying either scramble or Oma1-targeted shRNAs. Whole-cell lysates were analyzed by Western blotting using the indicated antibodies. The asterisk indicates non-specific bands of anti-Oma1 antibodies. ",
    "ncbi_link": "Drp1: 74006
Oma1: 67013"
  },
  {
    "caption": "(A) The mitochondrial membrane potential was measured in WT and Drp1-KO MEFs using a membrane potential-dependent dye (MitoLite NIR) and flow cytometry.",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (B) Drp1-KO MEFs carrying Su9-GFP were treated with DMSO (control) or 10 nM antimycin A or 10 ng/ml oligomycin for 1 h and viewed by laser scanning confocal microscopy for 30 min with 10-s intervals in the presence of TMRE. The arrows indicate mitochondria that showed flickering. Three frames from the time-lapse analysis are shown (please also see Movie EV1-EV4). Scale bar, 10 µm. ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (F) Drp1-KO MEFs were treated with DMSO or 10 nM antimycin A or 10 ng/ml oligomycin or 10 µM FCCP for 1 h. The mitochondrial membrane potential was analyzed using MitoLite NIR and flow cytometry. ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (G) Drp1-KO MEFs expressing L2-HA (induced for 16 h) were treated with 10 nM antimycin A along with 10 µM FCCP. Western blotting was performed using the indicated antibodies. The asterisk indicates non-specific bands of anti-Oma1 antibodies. (H) Quantification of band intensity. Values are average ± SD (n = 3). ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (I) Western blotting of Drp1-KO MEFs with or without 10 ng/ml oligomycin treatment. The asterisk indicates non-specific bands of anti-Oma1 antibodies. (J) Quantification of band intensity. Values are average ± SD (n = 3). ",
    "ncbi_link": "Drp1: 74006"
  },
  {
    "caption": " (K) WT MEFs carrying Su9-GFP were treated with DMSO or 10 ng/ml oligomycin for 1 h and viewed by laser scanning confocal microscopy for 30 min with 10-s intervals in the presence of TMRE. The arrows indicate mitochondria that showed flickering. Three frames from the time-lapse analysis are shown (please also see Movie EV1 and EV5). Scale bar, 10 µm. ",
    "ncbi_link": "GFP: "
  },
  {
    "caption": " (A) Western blotting of Drp1flox/floxOpa1flox/flox and Drp1Opa1-KO MEFs. The asterisk indicates non-specific bands of anti-Oma1 antibodies. (B) Quantification of band intensity. Values are average ± SD (n = 3). ",
    "ncbi_link": "Drp1: 74006
Opa1: 74143"
  },
  {
    "caption": " (C) Drp1flox/floxOpa1flox/flox MEFs and Drp1Opa1-KO MEFs were transduced with the indicated Opa1 constructs. The cells were observed using laser scanning confocal microscopy for 30 min with 10-s intervals in the presence of TMRE. The percentage of cells that exhibited flickering is shown. Values are average ± SD (n = 3 experiments). In each experiment, 48-62 cells were analyzed. ",
    "ncbi_link": "Drp1: 74006
Opa1: 74143"
  },
  {
    "caption": " (D) Drp1flox/floxOpa1flox/flox MEFs and Drp1Opa1-KO MEFs carrying the indicated Opa1 constructs were subjected to confocal immunofluorescence microscopy using anti-PDH antibodies. Scale bar, 10 µm. ",
    "ncbi_link": "Drp1: 74006
Opa1: 74143"
  },
  {
    "caption": " (G) Western blotting of Drp1flox/floxOpa1flox/flox MEFs and Drp1Opa1-KO MEFs, both of which carry the indicated Opa1 constructs. The asterisk indicates non-specific bands of anti-Oma1 antibodies. ",
    "ncbi_link": "Drp1: 74006
Opa1: 74143"
  },
  {
    "caption": " (A) Western blotting of WT MEFs and Drp1-KO MEFs, both of which carry shRNAs (Oma1 or scramble) and/or ectopic Mfn1. The asterisk indicates non-specific bands of anti-Oma1 antibodies. (B) Quantification of band intensity is shown. Values are average ± SD (n = 3). ",
    "ncbi_link": "Drp1: 74006
Oma1: 67013"
  },
  {
    "caption": " (C-F) WT MEFs (C and E) and Drp1-KO MEFs (D and F) were transduced with Su9-Eos, along with Oma1 shRNAs and ectopic Mfn1. Su9-Eos in the small region of mitochondria (indicated by the asterisks) was photoconverted using a 405-nm laser on confocal microscope. Within 1 s after photoconversion, images were obtained for both photoconverted and unconverted Su9-Eos signals. Images before the photoconversion were also taken to detect background signals. Scale bar, 10 µm. (E and F) To determine the connectivity of mitochondria, the area containing photoconverted Su9-Eos signals was divided by the area containing the photoconverted and unconverted Su9-Eos signals (total mitochondria). Values are average ± SD (n = 30 cells). ",
    "ncbi_link": "Drp1: 74006
Oma1: 67013"
  },
  {
    "caption": " WT which carry shRNAs (Oma1 or scramble) and ectopic Mfn1, were stained with TMRE. The percentage of cells that maintained the membrane potential is shown. Values are average ± SD (n = 3). 100-150 cells were analyzed in each experiment. ",
    "ncbi_link": "Oma1: 67013"
  },
  {
    "caption": " Drp1-KO MEFs which carry shRNAs (Oma1 or scramble) and ectopic Mfn1, were stained with TMRE. The arrows indicate cells that lost the mitochondrial membrane potential in (C). Scale bar, 10 µm. The percentage of cells that maintained the membrane potential is shown. Values are average ± SD (n = 3). 100-150 cells were analyzed in each experiment. ",
    "ncbi_link": "Drp1: 74006
Oma1: 67013"
  },
  {
    "caption": "(d) Self-association pattern of Beclin 1 in vivo. Both GFP- and AsRed-tagged full-length Beclin 1 are co-transfected into HEK 293T cells and their self-association is probed by co-IP using GFP antibody for immunoprecipitation, followed by western blot with anti-AsRed antibody.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "c) Pull-down assay to assess the competition between Beclin 1-Atg14L and Beclin 1-UVRAG complexes. Increasing amount of His6-tagged Beclin 1 CC domain was added to a mixture of Atg14L and UVRAG proteins corresponding to their respective CC region. The Beclin 1-Atg14L/UVRAG complexes were pulled down by Ni2+- nitrilotriacetic acid (NTA) agarose beads and checked by SDS gel.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(c) Self-association pattern of wild-type, MutM and MutStab constructs of Beclin 1 in vivo. For each construct, both GFP- and Myc-tagged full-length Beclin 1 are co-transfected into HEK 293T cells and their self-association is probed by co-IP using GFP antibody for IP, followed by western blot with anti-Myc antibody.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(a,b) Interaction of Beclin 1 wild-type and monomeric (MutM) mutants with Atg14L or UVRAG in cultured cells. HEK 293T cells were transfected with GFP-tagged Beclin 1 variant alone (a) or together with FLAG-UVRAG (b). The lysates were immunoprecipitated by GFP antibody, followed by western-blot analysis with anti-Atg14L antibody for detecting binding to endogenous Atg14L (a) or with anti-UVRAG antibody for detecting binding to the FLAG-tagged UVRAG protein (b).",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(a, b) Interaction of MutStab mutants of Beclin 1 with Atg14L or UVRAG in vivo. HEK 293T cells were transfected with GFP-tagged Beclin 1 variant alone (b) or together with FLAG-UVRAG (b). The lysates were immunoprecipitated by GFP antibody, followed by western blot analysis with anti-Atg14L antibody for detecting binding to endogenous Atg14L (a) or with anti-UVRAG antibody for detecting binding to the FLAG-tagged UVRAG protein (b).",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(a,b). Representative fluorescent images of HeLa cells co-tansfected with GFP-tagged Beclin 1 wild type, MutM L178A/L192A or MutStab E189L/A217L/E224L/A255L (green) and AsRed-Atg14L (red) (a) or FLAG-UVRAG (red) (b); Co-localization of AsRed-Atg14L with GFP-tagged Beclin 1 wild type or MutM is shown in discrete puncta.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(c-e) Representative fluorescence images of HeLa cells co-transfected with Myc-Beclin 1 wild type, MutM L178A/L192A or MutStab E189L/A217L/E224L/A255L (blue), AsRed-Atg14L (red) and GFP-tagged Atg12 (c). The scale bar is 20 μM.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "(c-e) Representative fluorescence images of HeLa cells co-transfected with Myc-Beclin 1 wild type, MutM L178A/L192A or MutStab E189L/A217L/E224L/A255L (blue), AsRed-Atg14L (red) and GFP-tagged LC3 (d) and DFCP (e) (green). The scale bar is 20 μM.",
    "ncbi_link": "Beclin 1: 114558"
  },
  {
    "caption": "Phenotypic analysis of ScUba4 mutant yeast strains in response to rapamycin.",
    "ncbi_link": "Uba4: 856511"
  },
  {
    "caption": "V-SVZ whole-mount staining showing reduced CCN1 expression in Ccn1cKO mice 1 week after TAM treatment. Scale bar: 10 μm.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "Densities (cells/mm2) of BrdU+ cells in the OB granule cell layer (GCL) 2 days after TAM treatment. n=4 (Ctrl) and 3 (Ccn1cKO), **p=0.0086. OB sections stained for BrdU (yellow) and nuclei (blue). Scale bar: 50 μm.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "Densities (cells/mm2) of BrdU+ cells in the OB GCL labeled 24h after TMZ treatment. n=5 (Ctrl) and 6 (Ccn1cKO), *p= 0.0484. OB sections stained for BrdU (yellow) and nuclei (blue). Scale bar: 50 μm.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "Densities (cells/mm2) of BrdU+ cells in the OB GCL of aged mice labeled 3 days after TMZ treatment. n=4 (Ctrl) and 3 (Ccn1cKO), n.s. not significant. Scale bar: 50 μm.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "Densities (cells/mm2) of VCAM1+ B1 cells in the adult V-SVZ whole-mounts. n=4 (Ctrl + vehicle and Ccn1cKO + vehicle) and 3 (Ccn1cKO + erlotinib), **p=0.0021 (Ccn1cKO + vehicle vs Ccn1cKO + erlotinib), **p=0.0014 (Ccn1cKO + erlotinib vs Ctrl + vehicle), ****p<0.0001.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "Densities (units/mm2) of NSC units in the adult V-SVZ whole-mounts. n=4 (Ctrl + vehicle and Ccn1cKO + vehicle) and 3 (Ccn1cKO + erlotinib), *p=0.017, **p=0.0061, ***p=0.0002.",
    "ncbi_link": "Ccn1: 16007"
  },
  {
    "caption": "(A) Dually labeled D. discoideum amoebae producing MCS components fused to GFP, and either calnexin  (CnxA)-mCherry  (pAW012), P4C-mCherry  (pWS032), or AmtA-mCherry  were infected (MOI 5, 2 h) with mCerulean-producing  L. pneumophila JR32   (pNP99), fixed with 4 % PFA, and imaged by confocal fluorescence microscopy. Merged images are shown. Scale bars: 3 μm (insets: 1 μm).",
    "ncbi_link": "mCerulean: "
  },
  {
    "caption": "(A) Dually labeled  D. discoideum Ax3  producing mCherry-Vap  (pSV048) and OSBP8-GFP  (pMIB89) or GFP-OSBP11  (pMIB39) were infected (MOI 5, 1-8 h) with mCerulean-producing  L. pneumophila JR32  (pNP99) and fixed with 4 % PFA. Merged images for the analyzed time points are shown. Scale bars: 3 μm (insets: 1 μm).",
    "ncbi_link": "mCerulean: "
  },
  {
    "caption": "(A) D. discoideum  Ax3, or the ∆vap, ∆osbG, ∆osbH, or ∆osbK mutant strains producing GFP  (pDM317) or GFP  fusions of the MCS components were infected (MOI 1) with mCherry-producing  L. pneumophila JR32 (pNP102), and intracellular replication was assessed by relative fluorescence units (RFU). Mean and SEM of three independent biological replicates are shown (statistics refer to JR32  infected  D. discoideum Ax3   producing GFP; *P<0.05; **P<0.01; ***P<0.001, Student`s t-test). To improve clarity, the different mutant strains are shown in separate graphs, each depicting the same data for Ax3/GFP.",
    "ncbi_link": "GFP: 
mCherry: 
osbG: 
osbH: 
osbK: 
vap: "
  },
  {
    "caption": "(B)  D. discoideum Ax3 producing CnxA-GFP  (pAW016), GFP-Sac1  (pLS037), GFP-Sac1_C383S (pSV015) or GFP-Sac1_ΔTMD (pSV034) were infected (MOI 1) with mCherry-producing  L. pneumophila JR32  (pNP102), and intracellular replication was assessed by relative fluorescence units (RFU). Mean and SEM of three independent biological replicates are shown (statistics refer to JR32  infected  D. discoideum Ax3 producing GFP-Sac1; ***P<0.001, Student`s t-test).",
    "ncbi_link": "GFP: 
mCherry: 
Sac1: 
CnxA: 8617897"
  },
  {
    "caption": "(C) RAW 264.7 macrophages  were treated with increasing concentrations of OSW-1 (0-100 nM, 1-60 h), infected (MOI 1) with GFP-producing L. pneumophila JR32 (pNT28), and intracellular replication was assessed by relative fluorescence units (RFU). Mean and SEM of three independent biological replicates are shown (statistics refer to infected cells treated with 0 nM OSW-1; *P<0.05; ***P<0.001, Student`s t-test).",
    "ncbi_link": "GFP: "
  },
  {
    "caption": "(A) Dually labeled D. discoideum Ax3, ∆vap, ∆osbG, ∆osbH, ∆osbK or ∆sey1  mutants producing P4C-mCherry  (pWS032) and CnxA-GFP  (pAW016), or Ax3  producing P4C-mCherry  and either GFP-Sac1 (pLS037), GFP-Sac1_C383S (pSV015) or GFP-Sac1_ΔTMD (pSV034) were infected (MOI 5, 2-16 h) with mCerulean-producing L. pneumophila JR32 (pNP99) and fixed with 4 % PFA. Merged images for the analyzed  time points  are shown. Scale bars: 3 μm. (B) LCV  area was measured using ImageJ (n=100-200 per condition from 3 independent biological replicates). Means and SEM of single cells are shown (**P<0.01; ***P<0.001, Student`s t-test).",
    "ncbi_link": "GFP: 
mCerulean: 
osbG: 
osbH: 
osbK: 
sey1: 
vap: 
Sac1: 8618030"
  },
  {
    "caption": "(A) Dually labeled D. discoideum Ax3, ∆vap, ∆osbG, ∆osbH, ∆osbK or ∆sey1  mutants producing P4C-mCherry  (pWS032) and GFP-Sac1  (pLS037) were infected (MOI 5, 2-16 h) with mCerulean-producing L. pneumophila JR32 (pNP99) and fixed with 4 % PFA. Merged images for the analyzed  time points are shown. Scale bars: 3 μm. (B, C) Imaging flow cytometry  (IFC) analysis of dually labeled D. discoideum Ax3, ∆vap, ∆osbG, ∆osbH, ∆osbK or ∆sey1 mutants producing P4C-mCherry  (pWS032) and either GFP-Sac1  (pLS037) or GFP-Sac1_ΔTMD (pSV034), infected (MOI 5, 2 h) with mPlum-producing L. pneumophila JR32 (pAW014). Data information (B, C, : Data represent mean and SEM of three independent biological replicates (*P<0.05; **P<0.01; ***P<0.001, Student`s t-test).",
    "ncbi_link": "GFP: 
mCerulean: 
mPlum: 
osbG: 
osbH: 
osbK: 
sey1: 
vap: 
Sac1: 8618030"
  },
  {
    "caption": "(D) Dually labeled  D. discoideum Ax3 producing GFP  fusions of MCS components and either mCherry-Sac1  (pSV044) or mCherry-Sac1_ΔTMD (pSV045) were infected (MOI 5, 2 h) with mCerulean-producing  L. pneumophila JR32  (pNP99) and fixed with 4 % PFA. Merged images for the analyzed  time points are shown. Scale bars: 3 μm. (E) IFC  analysis of dually labeled D. discoideum Ax3  producing GFP  fusions of MCS components and either mCherry-Sac1 (pSV044) or mCherry-Sac1_ΔTMD (pSV045), infected (MOI 5, 2 h) with mPlum-producing L. pneumophila JR32  (pAW014). Quantification of (B) P4C-mCherry  (C) Sac1-GFP  or (E) GFP  fusions of MCS components localizing  to LCVs  at 2 h p.i. Due to the lower resolution of IFC, \"LCVs\" designates the LCV  limiting membrane and tightly attached ER. Number of events per sample, n = 5000. Data information E): Data represent mean and SEM of three independent biological replicates (*P<0.05; **P<0.01; ***P<0.001, Student`s t-test).",
    "ncbi_link": "mCerulean: 
mCherry: 
mPlum: 
Sac1: 8618030"
  },
  {
    "caption": "(A) Dually labeled  D. discoideum Ax3 producing GFP-D4H* (pSV046) or P4C-GFP  (pWS034) and P4C-mCherry  (pWS032), CnxA-mCherry  (pAW012), or AmtA-mCherry  were infected (MOI 5, 15 - 120 min) with mCerulean-producing L. pneumophila JR32  (pNP99) and fixed with 4 % PFA. Merged images for the analyzed time points are shown. Scale bars: 3 μm. (B-C) The Pearson's correlation coefficient was generated using Coloc 2 from Fiji (ImageJ) and is shown for (B) AmtA-mCherry  with respect to P4C-GFP  or GFP-D4H* (n=100-150 per   time point), and (C) GFP-D4H* with respect to P4C-mCherry  or CnxA-mCherry  (n=100-150 each per time point). Data represent mean and SEM of three independent biological replicates (*P<0.05, Student`s t-test).",
    "ncbi_link": "mCerulean: "
  },
  {
    "caption": "(D) Single labeled D. discoideum Ax3 producing either CnxA-GFP  (pAW016) or P4C-GFP  (pWS034) were infected (MOI 5, 15-120 min) with mCherry-producing L. pneumophila JR32 (pNP102), fixed with 4 % PFA  and stained  with filipin. Merged images for the analyzed time points  are shown. Scale bars: 3 μm. (E) The Pearson's correlation coefficient was generated using Coloc 2 from Fiji (ImageJ) and is shown for filipin  with respect to CnxA-GFP  or P4C-GFP  (n=80-90 each per  time point). Data represent mean and SEM of the means of three independent biological replicates (***P<0.001, Student`s t-test).",
    "ncbi_link": "mCherry: "
  },
  {
    "caption": "(A) Dually labeled  D. discoideum Ax3  producing P4C-mCherry  (pWS032) and either CnxA-GFP  (pAW016), GFP-Sac1 (pLS037), or GFP-Sac1_ΔTMD (pSV034) were infected (MOI 5, 1-8 h) with mCerulean-producing L. pneumophila JR32, ΔlepB or ΔsidC (pNP99) and fixed with 4 % PFA. Merged images for the analyzed  time points are shown. Scale bars: 3 μm.",
    "ncbi_link": "GFP: 
mCerulean: 
lepB: 66491661
Sac1: 8618030
sidC: 66491684"
  },
  {
    "caption": "(C)  Imaging flow cytometry (IFC) analysis of dually labeled D. discoideum Ax3 producing P4C-mCherry  (pWS032) and either CnxA-GFP  (pAW016), GFP-Sac1 (pLS037), or GFP-Sac1_ΔTMD (pSV034), infected (MOI 5, 1-8 h) with mPlum-producing L. pneumophila JR32 (pAW014). Number of events per sample, n = 5000. Data represent mean and SEM of three independent biological replicates (*P<0.05; **P<0.01; ***P<0.001, Student`s t-test).",
    "ncbi_link": "GFP: 
mPlum: 
Sac1: 8618030"
  },
  {
    "caption": "(B) GALpr-Dfm1-BirA-Flag and GALpr-BirA-Flag levels were measured by western blotting with α -FLAG at 0 (uninduced) vs. 5 hours post-galactose induction (3 biological replicates; n=3).",
    "ncbi_link": "BirA: 
Flag: 
Dfm1: 852020
GAL: 855828"
  },
  {
    "caption": "(C) Dfm1-BirA is still functional and able to degrade Hmg2-GFP. dfm1Δ+Hmg2-GFP strains containing DFM1-BIRA, empty vector, or BIRA only addbacks were grown to log phase and degradation was measured by CHX. After CHX addition, cells were lysed at the indicated times and analyzed by SDS-PAGE and immunoblotted for Hmg2-GFP with α-GFP.",
    "ncbi_link": "BirA: 
BIRA: 
GFP: 
dfm1: 852020
Dfm1: 852020
DFM1: 852020
Hmg2: 851171"
  },
  {
    "caption": "(D) Yeast strains expressing Dfm1-Bira and BirA only negative control were incubated with different amounts of biotin: 0, 0.1, and 1 mM. dfm1Δ+Hmg2-GFP. Microsomes were isolated from each strain and subjected to streptavidin pulldown (3 biological replicates; n=3). Flow-through and pull-down fractions were detected by western blotting for Dfm1-BirA with α-Flag and Cdc48 with α-Cdc48 antibodies.",
    "ncbi_link": "Bira: 
BirA: 
GFP: 
Dfm1: 852020
dfm1: 852020
Hmg2: 851171"
  },
  {
    "caption": "(A) Dfm1-GFP binding to Lcb2-RFP and Orm2-RFP were analyzed by co-IP. As negative control, cells not expressing Dfm1-GFP were used (3 biological replicates; n=3).",
    "ncbi_link": "GFP: 
Dfm1: 852020"
  },
  {
    "caption": "(A) Indicated strains were spotted 5-fold dilutions on synthetic complete (SC) plates , and plates were incubated at room temperature, 30oC, and 37oC (3 biological replicates, 2 technical replicates; n=5). WT, dfm1∆, tsc3∆, and dfm1∆tsc3∆ were compared for growth in the dilution assay. Arrowhead indicates growth phenotype of tsc3∆ cells; open circle indicates growth phenotype of dfm1∆tsc3∆ cells. (B) dfm1∆tsc3∆ confers resistance to myrocin. WT, dfm1∆, tsc3∆, and dfm1∆tsc3∆ strains were grown to log-phase in YPD medium, and 5-fold serial dilutions of cultures were spotted on (SC) plates containing either drug vehicle alone, 1 µM of myriocin and 10 μM of PHS (3 biological replicates, 2 technical replicates; n=5). Arrowhead indicates growth phenotype of tsc3∆ cells; open circle indicates growth phenotype of dfm1∆tsc3∆ cells.",
    "ncbi_link": "dfm1: 852020
tsc3: 852350"
  },
  {
    "caption": "(D) Indicated strains were spotted 5-fold dilutions on SC plates in 3 biological replicates and 2 technical replicates (n=5), and plates were incubated at room temperature, 30oC, and 37oC (n=3). Upper panel: WT, orm1∆, tsc3∆, and orm1∆tsc3∆ were compared for growth by dilution assay. Middle panel: WT, orm2∆, tsc3∆, and orm2∆tsc3∆ were compared for growth by dilution assay. Bottom panel: WT, orm1∆, orm2∆, tsc3∆, and orm1∆orm2∆tsc3∆, were compared for growth by dilution assay. Upper panel: arrowhead indicates growth phenotype of tsc3∆ cells; open circle indicates growth phenotype of orm1∆tsc3∆ cells. Lower panel: arrowhead indicates growth phenotype of orm2∆ cells; open circle indicates growth phenotype of orm2∆tsc3∆ cells.",
    "ncbi_link": "orm1: 852926
orm2: 851064
tsc3: 852350"
  },
  {
    "caption": "(A) Indicated strains were spotted 5-fold dilutions on SC plates in 3 biological replicates and 2 technical replicates (n=5), and plates were incubated at room temperature, 30oC, and 37oC. Upper panel: WT, dfm1∆, orm1∆, and dfm1∆orm1∆ were compared for growth by dilution assay. Middle panel: WT, dfm1∆, orm2∆, and orm2∆tsc3∆ were compared for growth by dilution assay. Bottom panel: WT, dfm1∆, orm1∆, orm2∆, and orm2∆, and orm1∆orm2∆ were compared for growth by dilution assay. Upper, middle, and lower panel: gray arrowhead depicts growth phenotype of dfm1∆orm1∆, dfm1∆orm2∆, and orm1∆orm2∆ respectively. (B) dfm1∆orm1∆ confers resistance to myriocin and sensitivity to PHS. WT, dfm1∆, orm1∆, and dfm1∆orm1∆ strains were grown to log-phase in SC medium, and 5-fold serial dilutions of cultures were spotted on YPD plates containing either drug vehicle alone, 1 mM of myriocin and 10 μM of PHS with each condition performed in 3 biological replicates and 2 technical replicates (n=5). Plates were incubated at room temperature and photographed after 3 days. Open circle indicates growth phenotype of dfm1∆orm1∆ cells.",
    "ncbi_link": "dfm1: 852020
orm1: 852926
orm2: 851064
tsc3: 852350"
  },
  {
    "caption": "(A) Degradation of Orm2 depends on Dfm1 and not Der1. The indicated strains expressing Orm2-RFP were grown into log phase and degradation was measured by cycloheximide chase (CHX). After CHX addition, cells were lysed at the indicated times, and analyzed by SDS-PAGE and immunoblotted for Orm2-RFP with α-RFP (3 biological replicates (n=3). (B) Same as (A) except degradation of Orm2-RFP was measured in WT and der1∆ cells (3 biological replicates; n=3).",
    "ncbi_link": "der1: 852500
Der1: 852500
Dfm1: 852020"
  },
  {
    "caption": "(D) Dfm1's SHP box is not required for degradation of Orm2-RFP. In the indicated strains, degradation of Orm2-RFP was measured by CHX-chase assay. Cells were analyzed by SDS-PAGE and immunoblotted for Orm2-RFP with α-RFP (3 biological replicates; n=3).",
    "ncbi_link": "Dfm1: 852020"
  },
  {
    "caption": "(G) Dfm1's WR motif, GxxxG motif, substrate binding and lipid thinning function are required for degradation of Orm2-RFP. In the indicated strains, degradation of Orm2-RFP was measured by CHX-chase assay. Cells were analyzed by SDS-PAGE and immunoblotted for Orm2-RFP with α-RFP (3 biological replicates; n=3).",
    "ncbi_link": "Dfm1: 852020"
  },
  {
    "caption": "(H) Dfm1 L1 residues are required for binding to Orm2. Orm2-RFP and binding to retrotranslocation-deficient Dfm1 L1 mutants was analyzed by co-IP. The IP was analyzed for presence of Dfm1-HA. As a negative control, cells not expressing Orm2-RFP were used (3 biological replicates; n=3). Band intensities for all western blots were normalized to PGK1 loading control and quantified by ImageJ.",
    "ncbi_link": "Dfm1: 852020
Orm2: 851064"
  },
  {
    "caption": "(A) E3 ligase Tul1 is required for Orm2 degradation. In the indicated strains, degradation of Orm2-RFP was measured by CHX-chase assay. Cells were analyzed by SDS-PAGE and immunoblotted for Orm2-RFP with α-RFP (3 biological replicates; n=3). t=0 was taken as 100% and data is represented as mean ± SEM.",
    "ncbi_link": "Tul1: 853832"
  },
  {
    "caption": "(B) Cdc48 and the proteasome are required for Orm2 degradation. Same as (A), except cdc48-2 and hrd2-1 were analyzed for Orm2-RFP degradation (3 biological replicates; n=3). t=0 was taken as 100% and data is represented as mean ± SEM.",
    "ncbi_link": "cdc48: 851431
hrd2: 856422"
  },
  {
    "caption": "(C) Dfm1 does not function in the post-ubiquitination step of Orm2 degradation pathway. Indicated strains expressing Orm2-RFP were grown into log phase. Cells were lysed, and microsomes were collected and immunoprecipitated with α-RFP conjugated to agarose beads. Samples were then subjected to SDS-PAGE and immunoblot by α-Ubiquitin and α-RFP (3 biological replicates; n=3).",
    "ncbi_link": "Dfm1: 852020"
  },
  {
    "caption": "(D) ERAD mutants do not rescue temperature-sensitive lethality of tsc3∆. Indicated strains were grown to log-phase in SC and serially diluted cultures were plated on SC plates and incubated at 37°C and imaged at Day 2 (3 biological replicates, 2 technical replicates; n=5).",
    "ncbi_link": "tsc3: 852350"
  },
  {
    "caption": "(A) Phosphorylated Orm2 accumulates in the absence of Dfm1. Phos-tag western blot analysis shows that there is an accumulation of phosphorylated Orm2 in dfm1∆ cells. The indicated strains were grown to log phase, treated with vehicle or 1.5 μM myriocin for 1 hour and subjected to SDS-PAGE or Phos-tag western blot analysis via blotting for Orm2 with α-RFP and PGK1 with α-PGK1 antibodies (2 biological replicates; n=2).",
    "ncbi_link": "Dfm1: 852020
dfm1: 852020
Orm2: 851064"
  },
  {
    "caption": "(C) dfm1∆ cells block the degradation of phosphorylated mimic of Orm2 (Orm2-3D). In the indicated strains, degradation of Orm2-3A-GFP and Orm2-3D-GFP was measured by CHX-chase assay. Cells were analyzed by SDS-PAGE and immunoblotted α-GFP (3 biological replicates; n=3). t=0 was taken as 100% and data is represented as mean ± SEM.",
    "ncbi_link": "dfm1: 852020"
  },
  {
    "caption": "(A) Dfm1-HA binding to Orm2-GFP, Orm2-3A-GFP, Orm2-3D-GFP, Orm1, Lcb1, and Lcb2 were analyzed by co-IP. As negative control, cells not expressing Dfm1-HA were used. Also, Sec61 was also included to test for non-specific binding (3 biological replicates; n=3). (B) Same as (A), except co-IP was performed on WT and orm2∆ cells and Dfm1-HA binding to Orm1, Lcb1, and Lcb2 was analyzed (3 biological replicates; n=3). (C) Same as (A), except Orm2-GFP binding to Dfm1-HA, Orm1, Lcb1, and Lcb2 was analyzed by co-IP (3 biological replicates; n=3).",
    "ncbi_link": "GFP: 
HA: 
Dfm1: 852020
orm2: 851064
Orm2: 851064"
  },
  {
    "caption": "(a) Fold change in gene expressions of CXCL10, CXCL11, CXCL12, CCL20 and CX3CL1 in NAFLD (n = 10) BOECs, normalized to healthy (n = 12) BOECs, with 2 technical replicates per donor. (c) Fold change in gene expressions of CXCL10, CXCL11, CXCL12, CCL20 and CX3CL1 in LPS+FFA-treated or non-treated NAFLD (n = 5) and healthy (n = 5) BOECs, normalized to non-treated healthy BOECs, with 3 technical replicates per donor.",
    "ncbi_link": "CCL20: 6364
CX3CL1: 6376
CXCL10: 3627
CXCL11: 6373
CXCL12: 6387"
  },
  {
    "caption": "(a) Upper panel: Single-cell UMAP of sequenced PBMCs from 2 NAFLD patients and 4 healthy subjects; n = 10,786 cells. We identified 15 distinct cell types by DICE annotation. Lower panel: Expression patterns of CXCR3, CXCR4, ACKR3, CX3CR1, CCR6 across different cell types in NAFLD and healthy PBMC samples.",
    "ncbi_link": "ACKR3: 57007
CCR6: 1235
CX3CR1: 1524
CXCR3: 2833
CXCR4: 7852"
  },
  {
    "caption": "A) IFNγ  cytokine measured in the amniotic fluid  (AF)  and fetal liver supernatant  (FL) of IFNγKO (IFNγ-/-) mice  one day following injection of cytokine on E14.5. ND = not detectable. Data represent mean of 3 fetuses/condition and error bars represent + SD.",
    "ncbi_link": "IFNγ: 15978"
  },
  {
    "caption": "C-H) Total cellularity of C) HSPCs, D) LT-HSCs, E) ST-HSCs, F) MPP2, G) MPP3, and H) MPP4  in saline  or IFNγ  exposed littermates of each genotype (IFNγ  +/- or -/-), as derived from the cross (IFNγR +/- dam). n = 19-23 fetuses  from 3 litters/condition.",
    "ncbi_link": "IFNγ: 15979
IFNγR: 15979"
  },
  {
    "caption": "J-O) Total cellularity of J) HSPCs, K) LT-HSCs, L) ST-HSCs, M) MPP2, N) MPP3, and O) MPP4  in saline  or IFNγ  exposed littermates of each genotype (IFNγ  +/- or -/-), (IFNγR  -/- dam). n = 19-21 fetuses  from 3 litters/condition. For all analysis bars represent mean. Statistical significance was determined by unpaired student's t-test. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001.",
    "ncbi_link": "IFNγ: 15979
IFNγR: 15979"
  },
  {
    "caption": "(B) Quantitative PCR analysis of post-natal lungs for mitochondrial DNA (mtDNA). Actin was used as a normalization control. (mean ± SD, : p<0.05;: p<0.01; N=3).",
    "ncbi_link": "Actin: "
  },
  {
    "caption": "(D) Quantitative analysis of the efficiency of NHEJ-repair in a reporter cell line, as described in Methods. Cells were cultured in low glucose (5.5mM) or high glucose (30mM) for 5 days, fructose (30mM), ribose (20mM), for 3 days (graph bar 4). I-SceI, untransfected cells served as a negative control. Shown is the average from three independent experiments (mean ± SEM, : p<0.01 : p<0.001).",
    "ncbi_link": "I-SceI: 854590"
  },
  {
    "caption": "(A) Representative images of γH2AX positive nuclei in lungs of 6-month STZ induced diabetic mice, transduced with respective RAGE virions as described in Methods. The lungs were harvested 6-weeks after viral transduction. The empty vector served as control. Red represents γH2AX foci green cytoplasmic staining represents α-tubulin; blue nuclear staining represents DAPI (Scale 10µm). No primary antibody control served as a negative control (from control lung) of the staining.",
    "ncbi_link": "RAGE: 11596"
  },
  {
    "caption": "(C) Representative images of lungs from 6-month STZ induced diabetic mice, transduced with respective RAGE virions as described in Methods. Lungs were stained for cellular senescence-associated β-galactosidase as described in Figure 5a and visualized by bright field and polarized light, where the accumulated senescent areas are recognized by its blue staining (Scale 40µm).",
    "ncbi_link": "RAGE: 11596"
  },
  {
    "caption": "(E) Quantitative analysis of Masson's Trichrome stain for lungs of 6-month STZ induced diabetic mice with respective RAGE virions as described in Figure 5F (mean ± SD, : p<0.001; N=8).",
    "ncbi_link": "RAGE: 11596"
  },
  {
    "caption": "(F) Representative images of Masson's Trichrome stain for lungs transduced with the respective RAGE expressing virions as described in Figure 5a and visualized by bright field and polarized light, where the accumulated ECM areas are recognized by its blue staining (Scale 40µm). The dotted lines represent the respective zoomed window.",
    "ncbi_link": "RAGE: 11596"
  },
  {
    "caption": "(G) Pressure-volume curves of diabetic and non-diabetic mice were determined using the FlexiVent system 6 weeks after transduction using respective the RAGE virions, as described in Figure 5a. The curves represent group averages (N=8). The lungs studied in Figure 5a, b, c and d are identical (mean ± SD; Vector alone vs. RAGE-EE; : p<0.05; N=8).",
    "ncbi_link": "RAGE: 11596"
  },
  {
    "caption": "J-L) mRNA expression of p21 (j), IL-6 (k) and IL-8 (l) 20 days after neutrophil co-culture; Data are mean±S.E.M. of 2-3 independent experiments.",
    "ncbi_link": "p21: 1026
IL-8: 3576
IL-6: 3569"
  },
  {
    "caption": "i) Comparison between p16Ink4a mRNA levels of young (3 months old) and old INK-ATTAC mice (28-29 month old) treated with vehicle or AP20187. Data are mean ± SEM of n = 5-8 mice per age group; j) % of TAF positive hepatocytes in old INK-ATTAC mice (28-29 months old) treated with vehicle or AP20187. Data are mean ± SEM of n = 5-6 mice per group; k) Liver neutrophils (Ly6G) in old INK-ATTAC mice (28-29 months old) treated with vehicle or AP20187. Data are mean ± SEM of n = 5-7 mice per group; ",
    "ncbi_link": "p16Ink4a: 12578"
  },
  {
    "caption": "A Lysates from RK13 cells transfected with WT, S1, S3 and S3.F88W PrP were probed with antibody Sha31, 9A2 and 12B2 after digestion with PNGaseF.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B, C Additional PrP mutants were examined by Western blot with Sha31 after PNGaseF digestion of RK13 cell lysates. A schematic of the different lengths of C2 caused by single mutations in the OR is shown in the lower portion of (C).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B, C Additional PrP mutants were examined by Western blot with Sha31 after PNGaseF digestion of RK13 cell lysates. A schematic of the different lengths of C2 caused by single mutations in the OR is shown in the lower portion of (C).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "D Lysates of N2a, HEK, SMB-PS and SH-SY5Y cells not transfected (−) and transiently transfected with WT PrP or S3 PrP plasmids were digested with PNGaseF and analysed by Western blot using Sha31.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "E Analysis of lysates from RK13 cells transfected with plasmids incorporating Phe substitutions into the hydrophobic domain of WT PrP, S1 PrP and S3 PrP. Lysates were PNGaseF-digested before Western blot using the Sha31 antibody. F1: A114F, F2: G118F, F3: G122F, F4: G126F",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A Brain homogenates of TgPrP(WT), TgPrP(S1)-17 and TgPrP(S3.F88W)-35 mice were analysed by Western blot before and after PNGaseF digestion using the PrP antibodies Sha31, 12B2 and 9A2. Prnp0/0, and WT brain homogenates were used as controls.",
    "ncbi_link": "Prnp: 19122
PrP: 19122"
  },
  {
    "caption": "B The ratio of C2 to full-length PrP in TgPrP(S3.F88W)-35 and WT mice (left panel, n = 7, P = 1.46E-06) and in RK13 cells expressing WT and S3 PrP (right panel, n = 5, P = 4.01E-05) is shown. Values are presented as mean ± SEM. Unpaired, two-tailed t-test, ****P < 0.0001.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "C Different tissue homogenates from a TgPrP(S3.F88W)-35 mouse were PNGaseF-digested and analysed for PrP using the antibody 1A6. FL, full-length PrP; ns, non-specific signal detected in the immunoblotting procedure.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A Sections of sciatic nerve from TgPrP(S3.F88W)-14 female mice (all 610 days old) and TgPrP(S3.F88W)-35 female mice (614, 570 and 614 days old, respectively) were analysed using toluidine blue staining (upper row), with the third panels for each line showing a hypermyelinated phenotype. Scale bar in left panel represents 50 μm. The lower rows show EM analyses of mice of the indicated genotypes. Scale bar is 10 μm for panels 1-4, with the fifth panel showing a high power view to illustrate hypermyelinated fibres in a mouse expressing S3.F88W PrP (scale bar, 5 μm).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B Western blot analysis of sciatic nerve protein extracts (10 μg) from female mice after PNGaseF treatment shows a similar hierarchy of PrP expression in Tg lines to that of brain (see Fig3). The asterisk indicates a greater than full-length fragment present in TgPrP(S3.F88W) mice, possibly corresponding to incomplete removal of the N-terminal signal peptide.",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "C Quantification of fibre morphology in aged animals (492-608 days old), representing the percentage of the nerve occupied by fibres versus the total cross-sectional area of the nerve. The S1 and S3.F88W alleles rescue Prnp0/0 nerves to a similar percentage as the WT allele, but the variance and P-value is greater for the two Tg lines expressing the TgPrP(S3.F88W) allele. Unpaired, two-tailed t-test, **P < 0.01, ***P < 0.001, ****P < 0.0001. Sample sizes and exact P-values compared with Prnp0/0 (n = 9) were as follows: TgPrP(WT) n = 6, P = 3.63E-05; Prnp0/0, n = 9; TgPrP(S1)-17 n = 5, P = 3.54E-05; TgPrP(S1)-19 n = 3, P = 6.35E-06; TgPrP(S3.F88W)-14 n = 3, P = 3.70E-03; and TgPrP(S3.F88W)-35 n = 7, P = 7.18E-03.",
    "ncbi_link": "Prnp: 19122
PrP: 19122"
  },
  {
    "caption": "Pathology of RML-infected miceA-H The pattern of PrPSc deposition (A-D) and GFAP immunostaining (E-H) is presented.I-P A higher power view of H&E stained hippocampus (I-L) and thalamus (M-P) to reveal vacuolation is presented.Data information: Animals of the same genotype are shown within a column, and incubation times of the presented animals with the RML prion isolate are shown (days). Mice expressing PrP S1 and S3 alleles (central columns) exhibit attenuated PrPSc deposition, gliosis and spongy change. Pathological features of the RML isolate are not altered upon sequential passage through TgPrP(S3.88W)-35 mice (see schematic at bottom of the diagram indicating sequential passages and finally, passage back into WT mice, compare the data in first and fourth columns).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A Spot counts in the scrapie cell assay using WT, TgPrP(S1)-17 and TgPrP(S3.F88W)-14 brain homogenates (0.1% or 0.01%) from mice infected with RML are shown in the upper panel (WT vs S1 P = 2.09E-05 and vs S3 P = 4.62E-08) with numbers corrected for PrPC expression levels as per Table1 presented in the lower panel (WT vs S1 P = 1.04E-13 and vs S3 P = 3.39E-20; two-tailed t-test, n = 3).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "B A comparison of incubation time vs PrPC:PrPSc ratio for mice expressing different levels of WT PrP (WT, TgPrP(WT), tga20), S1 PrP (TgPrP(S1)-17, TgPrP(S1)-19, TgPrP(S1)-39) and S3 PrP (TgPrP(S3.F88W)-14, TgPrP(S3.F88W)-35).",
    "ncbi_link": "PrP: 19122"
  },
  {
    "caption": "A: Relative expression of ELDR in OSCC patient samples compared to adjacent non-tumor tissues (N=20) analyzed by qRT-PCR. Technical triplicates were used from each sample. 18S rRNA was used as an internal control. Data were analyzed by Student's t test. Small bars indicate standard error (*, p<0.05, **, p<0.01; *** p<0.001).",
    "ncbi_link": "18S rRNA: 
ELDR: 102725541"
  },
  {
    "caption": "B: OSCC grade wise upregulation of ELDR expression was noted in the patient samples (N=20). Correlation analysis showed signification positive correlation of ELDR expression with tumor grade (R2= 0.926, significant P value = 0.01). Pearson correlation coefficient and p value was calculated using socscistatistics.com. Well: well differentiated, Mod: moderately differentiated, Poor: poorly differentiated carcinoma. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "C: Representative images of FISH analysis with an RNA probe of ELDR (red) and DAPI staining (blue) in formalin fixed paraffin embedded OSCC tissue. An unrelated probe was used as negative control. Magnification: 40X; inset magnification 100X and scale bar 10 µm.",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "D: Relative expression of ELDR in OSCC cell lines compared to normal oral keratinocytes (NOK) analyzed by qRT-PCR. 18S was used as internal control. Data were analyzed by Student's t test. Small bars indicate standard error (**, p<0.01; *** p<0.001). n = 4 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "18S: 
ELDR: 102725541"
  },
  {
    "caption": "A: Control or ELDR plasmid DNA stably transfected NOKs were analyzed for cell proliferation using Trypan blue exclusion at the indicated time points. Live cell numbers are presented. n = 4 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "B: Control or ELDR plasmid DNA overexpressed NOK (3×102) were seeded and allowed to form colonies. After two weeks, colonies were stained with crystal violet and counted. Representative images of colonies in control and ELDR overexpressed cells are presented. The right panel shows quantitation. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "C: Cal27, JHU029 and JHU022 cells were transfected with control or ELDR siRNA (50nM), and cell proliferation was analyzed at the indicated time points. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "D: Cell lysates from control or ELDR overexpressing NOKs, control or Cal27 and JHU029 cells treated with two different ELDR siRNAs were subjected to Western blot analysis for PCNA expression using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control for normalization. The bottom panel shows a quantitative representation of Western blot band intensities. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "E: Cal27 and JHU029 cells were transfected with siELDR, ELDR plasmid DNA or both siELDR and ELDR plasmid DNA. Cell lysates were analyzed by Western blot for PCNA expression using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. The right panel shows quantitative representation of Western blot band intensities. n = 2 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "A: Cal27 or JHU029 cells were transfected with control or ELDR siRNA, and EGFR mRNA expression was examined by qRT-PCR. 18S gene was used as internal control. n = 3 biological replicates and 3 technical repeates.",
    "ncbi_link": "18S: 
EGFR: 1956
ELDR: 102725541"
  },
  {
    "caption": "B: Cell lysates from control and ELDR depleted Cal27 or JHU029 cells using two different siRNAs to ELDR were subjected to Western blot analysis for the EGFR using specific antibodies. The membrane was reprobed with an antibody against Actin as an internal control. The same actin blot was used in Fig. 2D (for PCNA). The bottom panel shows a quantitative representation of Western blot band intensities. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "C: Cal27 and JHU029 cells were transfected with siELDR, ELDR plasmid or both siELDR and ELDR plasmid. Cell lysates were analyzed by Western blot analysis for EGFR expression using specific antibody. The membrane was reprobed with an antibody against Actin as internal control. The same actin blot was used in Fig. 2E (for PCNA). n = 2 biological replicates.",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "D: Cell lysates from control and ELDR overexpressed NOK were subjected to Western blot analysis for the EGFR using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. The right panel shows a quantitative representation of Western blot band intensities. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "E: Cell lysates from control and ELDR-depleted Cal27 and JHU029 cells were subjected to Western blot analysis for phsospho-STAT3 (pSTAT3 Y-705) and total STAT3 using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. Right panel shows a quantitative representation of Western blot band intensities. n = 2 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "C: Cell lysates from Cal27 and JHU022 cells were incubated with biotinylated ELDR sense and antisense RNA, pulled down and subjected to Western blot analysis for the ILF3 using specific antibodies. Bottom panel shows Western blot analysis of PUM-1 (an unrelated RNA binding protein).",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "D: Cal27 and JHU022 cell lysates were immunoprecipitated against control or ILF3 antibody and RNA was isolated from the precipitates. Relative expression of ELDR (left penal) and PCAT1 (right panel) was analyzed by qRT-PCR. n = 3 biological replicates and 3 technical replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541
PCAT1: 100750225"
  },
  {
    "caption": "E: Cell lysates from control and ELDR depleted Cal27 and JHU029 cells were subjected to Western blot analysis for ILF3 using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. Right panel shows the quantitative representation of Western blot band intensities. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "F: Control, ELDR overexpressed and ELDR-depleted Cal27 cells were probed with an antibody against ILF3 (red) and DAPI (blue). Representative confocal microscopic images show nuclear and cytoplasmic expression of ILF3. Arrows indicate cytoplasmic expression. Magnifications 60X, scale bar 20 μ.",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "A: Cal27 and JHU022 cell lysates were immunoprecipitated with control or ILF3 antibodies and RNA was isolated from the precipitates. Relative mRNA expression of EGFR was analyzed by qRT-PCR. n = 3 biological replicates and 3 technical replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "B: Cal27 and JHU029 cells were transfected with control or ILF3 siRNA and after 48hr cell lysates were subjected to Western blot analysis for EGFR and ILF3 using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. n = 3 biological replicates.",
    "ncbi_link": "ILF3: 3609"
  },
  {
    "caption": "C: Cal27 and JHU029 cell lysates were transfected with either siELDR or siILF3 and relative mRNA expression of Cyclin E1 was analyzed by qRT-PCR. 18S was used as internal control. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "18S: 
Cyclin E1: 898
ELDR: 102725541
ILF3: 3609"
  },
  {
    "caption": "D: Control or ELDR depleted Cal27 and JHU029 cell lysates using two different siRNAs to ELDR were subjected to Western blot analysis for Cyclin E1 using specific antibody. The membrane was reprobed with an antibody against Actin as an internal control. Bottom panels show quantitation. n = 4 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "E: Control or ELDR overexpressed NOK lysates were subjected to Western blot analysis for Cyclin E1 using specific antibody. The membrane was reprobed with an antibody against Actin as internal control. Bottom panel shows quantitation. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "F: Control or ILF3depleted Cal27 and JHU029 cell lysates were subjected to Western blot analysis for Cyclin E1 using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. Bottom panels show quantitation. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ILF3: 3609"
  },
  {
    "caption": "G: Cal27 and JHU029 cells were transfected with either siELDR or siILF3 and after 48hr cell lysates were subjected to Western blot analysis for phospho-RB and total RB using specific antibodies. The membrane was reprobed with an antibody against Actin as internal control. Bottom panels show quantitation. n = 3 biological replicates. Data are represented as the mean ± SD",
    "ncbi_link": "ELDR: 102725541
ILF3: 3609"
  },
  {
    "caption": "H: Control or ELDR knockdown synchronized Cal27 and JHU029 cells were harvested, fixed and stained with propidium iodide. DNA content was analyzed by flow cytometry. Results are represented cell population in G1, S, and G2/M phases of the cell cycle. Right panels show percentage of cell population in different phases of cell cycle. n = 4 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "A: Cal27 and JHU029 cells were transfected with control or ELDR siRNA and relative expression of miR-7 was analyzed by qRT-PCR. U47 was used as an internal control. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "U47: 
ELDR: 102725541
miR-7: 407044"
  },
  {
    "caption": "B: Cal27 and JHU029 cells were transfected with control or ELDR plasmid and relative expression of miR-7 was analyzed by qRT-PCR. U47 was used as an internal control. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "U47: 
ELDR: 102725541
miR-7: 407044"
  },
  {
    "caption": "C: Cal27 and JHU029 cells were transfected with control or mimic miR-7 and relative expression of ELDR was analyzed by qRT-PCR. 18S rRNA was used as an internal control. n = 2 biological replicates; n= 3 technical replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "18S rRNA: 
ELDR: 102725541
miR-7: 407044"
  },
  {
    "caption": "D: Cal27 and JHU029 cells were transfected with miR-7 mimic, ELDR plasmid or both miR-7 and ELDR plasmid. Cell lysates were analyzed by Western blot analysis for EGFR expression using specific antibody. The membrane was reprobed with an antibody against Actin as an internal control. Representative bands were cropped from same gel. Right panels show quantitative representation of Western blot band intensities. n = 3 biological replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "ELDR: 102725541
miR-7: 407044"
  },
  {
    "caption": "E: Relative expression of miR-7 in Cal27 and JHU029 cells compared to NOK cell line analyzed by qRT-PCR. U47 was used as an internal control. n = 3 biological replicates and 3 technical replicates. Data are represented as the mean ± SD,",
    "ncbi_link": "U47: 
miR-7: 407044"
  },
  {
    "caption": "A: Body weight was measured in control and siELDR treated mice. n=5 animal per group",
    "ncbi_link": "ELDR: 102725541"
  },
  {
    "caption": "C: Tumors were measured using a slide caliper and tumor volumes were calculated. Arrow indicates starting point siELDR treatment. n=5 animal per group and tumor volume presented as the mean ± SD",
    "ncbi_link": "ELDR: 72735"
  },
  {
    "caption": "D: ELDR knockdown was examined by analyzing expression of ELDR in treated tumors compared to the control tumors. 18S rRNA gene was used as internal control. n=5 animal per group and 3 technical replicates from each tumor.",
    "ncbi_link": "18S rRNA: 
ELDR: 72735"
  },
  {
    "caption": "E: Control or siELDR treated tumor lysates were subjected to Western blot analysis for EGFR and Cyclin E1expression using specific antibodies and representative bands are shown. The blot was reprobed with an antibody against Actin for normalization. Right panels show quantitation. n= 3 biological replicates from each tumor",
    "ncbi_link": "ELDR: 72735"
  },
  {
    "caption": "F: OSCC-PDX tissue was implanted subcutaneously into the flank of NSG mice. When the tumor volume reached >70 mm3, mice were divided into two groups. 10µg of siELDR or control oligoes were injected intratumorally as described above. Body weight was measured in control and siELDR treated mice. n=5 animal per group",
    "ncbi_link": "ELDR: 72735"
  },
  {
    "caption": "I: ELDR knockdown was examined by analyzing expression of ELDR in treated OSCC-PDX tumors compared to the control tumors. 18S gene was used as internal control. n=5 animal per group and 3 technical replicates presented as the mean ± SD",
    "ncbi_link": "18S: 
ELDR: 72735"
  },
  {
    "caption": "D-F. Volcano plots showing RNA-seq data in mouse islets    (20% vs 5% O2  for 24 hours; n = 3 mice/group; D), human islets    (20% [n = 2 biological replicates from donor 1 sample] vs 2% [n = 3 biological replicates from donor 1 sample] O2  for 24 hours; E), and MIN6  cells (20% vs 5% O2  for 6 hours; n = 3 biological replicates; F). Atf3, Bhlhe40, and other reported hypoxia-inducible transcriptional repressor genes (Cavadas et al., 2017) are shown (red, significantly upregulated genes).",
    "ncbi_link": "Atf3: 11910
Bhlhe40: 20893"
  },
  {
    "caption": "D-F. The effect of oxidative stress, endoplasmic reticulum stress, and energy stress on BHLHE40  expression. qRT-PCR analysis of Bhlhe40  in MIN6  cells incubated with 10μM H2O2  (n = 3 biological replicates; D), 2μM thapsigargin  (Thap) or 5 μg/ml tunicamycin (Tun) (n = 7 biological replicates; E), or 2mM metformin  (Met) for 24 hours (n = 3 biological replicates; F). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "Bhlhe40: 20893
BHLHE40: 20893"
  },
  {
    "caption": "H-K. BHLHE40  expression  in islets  from diabetic mice. BHLHE40   expression  was analyzed in ob/ob mouse islets   by qRT-PCR (n = 4 biological replicates; H) and  Western blotting  (I) and in db/db mouse islets   by Western blotting (J). Subcellular localization  of BHLHE40  in ob/ob mice islets   by immunohistochemical  analysis (K). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. β-actin was used as a loading control. Scale bar, 100 μm.",
    "ncbi_link": "BHLHE40: 20893"
  },
  {
    "caption": "A. Glucose-stimulated insulin  secretion in MIN6  cells expressing short hairpin RNA against a non-targeting Ctrl or Bhlhe40   knockdown (B40  KD) were cultured under 20% or 5% O2  for 24 hours (n = 8 biological replicates). B. Glucose-stimulated insulin  secretion in MIN6  cells infected with retroviruses  generated with pMx-Ctrl (Ctrl) or pMx-Bhlhe40  (B40  OE; n = 4 biological replicates). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "B40: 20893
Bhlhe40: 20893"
  },
  {
    "caption": "D. KCl-stimulated insulin  secretion in Ctrl and B40   OE MIN6  cells (n = 3 biological replicates). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "G. Cellular ATP  content in Ctrl and B40   KD MIN6  cells cultured under 20% or 5% O2  for 24 hours (n = 3 biological replicates). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "I-K. Mitochondrial DNA (mtDNA) content (n = 4 biological replicates; I), mitochondrial  mass (n = 4 biological replicates; J), and mitochondrial membrane potential (n = 4 biological replicates; K) in Ctrl and B40   KD MIN6  cells cultured under 20% or 5% O2  for 24 hours. Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "B, Expression of DEGs shown in A was confirmed by qRT-PCR in Ctrl and B40   OE MIN6  cells (n = 3 biological replicates; B) Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01 and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "D. qRT-PCR of MAFA  target genes in Ctrl and B40  KD MIN6  cells cultured under 20% or 5% O2  for 24 hours (n = 3 biological replicates). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01 and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "G. Western blot of oxidative phosphorylation complex proteins and TOM20  protein in Ctrl and B40  KD MIN6  cells cultured under 20% or 5% O2  for 24 hours, and quantification of the band intensities (n = 3 biological replicates). Data information: Data are mean ± SEM; *p < 0.05, **p < 0.01 and ***p < 0.001 by unpaired two-tailed Student's t test. β-actin  was used as a loading control. Ctrl, control.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "C. Luciferase reporter assay  was performed with MIN6  cells transfected with BHLHE40   expression plasmids, pRL-SV40 plasmid, and pGL3-Mafa  plasmids (wildtype [black] and E-box mutated [red] sites; n = 4 biological replicates). D. Luciferase reporter activity  in MIN6  cells cultured under 20% or 5% O2  for 24 hours (n = 3 biological replicates). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "BHLHE40: 20893
Mafa: 378435"
  },
  {
    "caption": "H-J. Proteins sampled from Ctrl and B40  OE MIN6  cells with FLAG-Pdx1   expression (H) or from MIN6  cells with FLAG-Pdx1   expression pre-cultured under 20% or 5% O2  for 24 hours (I) were  immuno-precipitated  by IgG or anti-FLAG  antibody, after which qRT-PCR  was performed for the indicated regions (n = 9 biological replicates for H and n = 6 biological replicates for I). FLAG  (PDX1) expression in I was confirmed by Western blotting (J). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Ctrl, control; n.s., not significant.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "C, D.  Glucose tolerance test  of Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 9 mice  and n = 8 mice, respectively; 6 weeks old) (C) and AUC (D). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "E. Glucose-stimulated insulin  secretion in Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 9 mice  and n = 6 mice, respectively; 8 weeks old). F. Glucose-stimulated insulin  secretion in isolated islets   from Ctrl and βB40KO mice  after culture under 5% O2  for 24 hours (n = 8 biological replicates). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "I, J. Representative images of  pancreatic islets stained  for insulin  and glucagon  in Ctrl:ob/ob  and βB40KO:ob/ob mice  (12 weeks old) (I). The ratios of total islet  area to whole pancreas  area (%) are shown (n = 3 biological replicates; J). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Scale bar, 10 μm.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "K, L. Representative images of pancreatic islets stained  for insulin, MAFA, and BHLHE40  in Ctrl:ob/ob  and βB40KO:ob/ob mice  (12 weeks old) (K). Fluorescence intensities of nuclear  and cytosolic MAFA  in K were quantified (n = 30 cells; L). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test. Scale bar, 10 μm.",
    "ncbi_link": "B40: 20893"
  },
  {
    "caption": "M. qRT-PCR  of Mafa  and its target genes in Ctrl:ob/ob  and βB40KO:ob/ob mice  (n = 4 mice). Data information: Data are mean ± SEM; *p < 0.05 **p < 0.01, and ***p < 0.001 by unpaired two-tailed Student's t test.",
    "ncbi_link": "B40: 20893
Mafa: 378435"
  },
  {
    "caption": "A) Transmission electron microscopy (TEM) of MoDCs infected with P. gingivalis for 2, 12 and 24 hours (left, middle and right panels). The sections show the intra-and extra-cellular contents of Cont. (un-infected), Pg381, Mfa1+Pg and FimA+Pg infected MoDCs for the different time points",
    "ncbi_link": "Mfa1: 2551415
FimA: 2551422"
  },
  {
    "caption": "A) DC-SIGN mRNA expression in P. gingivalis-infected MoDCs at 0.1, 1 and 10 MOIs. The figure shows the gene expression after 12 hours of Pg381 and mutant strains infections. The target gene (DC-SIGN) was normalized using the endogenous control GAPDH (ΔCt) and fold regulations were calculated using 2-(ΔΔCt) method. The statistical analysis was performed using the t-test, which accounts for the clustering of infected and un-infected controls within 3 different experiments (* p<0.001).",
    "ncbi_link": "DC-SIGN: 30835
GAPDH: 2597"
  },
  {
    "caption": "B) Immuno-electron microscopy of un-infected MoDCs (Cont.) (upper panel), MoDCs infected with Pg381 (middle panel) and Mfa1+Pg mutants (lower panel). Gold particles (marked with red rings) for positive DC-SIGN were detected in the cell membrane and cytoplasm of cells infected with Mfa1+Pg strains. Minimal positive staining for DC-SIGN was detected in the membranes of MoDCs infected with Pg381, while no cytoplasmic gold labeling was detected in these cells.",
    "ncbi_link": "Mfa1: 2551415"
  },
  {
    "caption": "C) Flow cytometry analysis of surface DC-SIGN in human MoDCs after infection with Pg381, Mfa1+Pg and FimA+Pg. The analysis of the intensity used Kruskal-Wallis test analysis of different groups and Dunn's test for multiple comparisons 3 different experiments (* p<0.01).",
    "ncbi_link": "Mfa1: 2551415
FimA: 2551422"
  },
  {
    "caption": "The effect of rapamycin on Mfa1+Pg, Pg381 and FimA+Pg survival within MoDCs are shown in figures B, C and D respectively. A three-factor repeated measures ANOVA using mixed models was used to test the effect of strain and rapamycin treatment over time on OD reading. The survival curves for the strains are showed in blue, while the effect of rapamycin treatments are in red. Bacterial survivals in the absence of MoDCs with and without rapamycin are plotted in grey and black, respectively. Statistical analysis showed that the strain by rapamycin treatment overtime interaction indicates the pattern of means in each strain (Mfa1+Pg, Pg381 and FimA+Pg) between treated (rapamycin) and untreated were significantly different overtime (p-value <0.=001).",
    "ncbi_link": "Mfa1: 2551415
FimA: 2551422"
  },
  {
    "caption": "A) Epifluorescence microscopy images of MoDCs infected with Pg381, Mfa1+Pg, FimA+Pg and MFB strains after 12 hours. LC3-II was detected in red-fluorescent (Texas red) dye and the bacterial strains were pre-labeled with CFSE (green). Co-localization of P. gingivalis and LC3-II showed in the right panels.",
    "ncbi_link": "Mfa1: 2551415
FimA: 2551422"
  },
  {
    "caption": "A) Immuno-fluorescence images of LC3-II and P. gingivalis within MoDCs pre-treated with GP120 (DC-SIGN blocker) after 12 hours of infection. LC3-II was detected in red-fluorescent dye and the bacterial strains were pre-labeled with green CFSE.",
    "ncbi_link": "DC-SIGN: 30835"
  },
  {
    "caption": "C) Flow cytometry of MoDCs treated with siRNA for DC-SIGN (si-DC-SIGN) after 12 hours. Left panels show the decrease of DC-SIGN in Cont. (un-infected), Pg381 and Mfa1+Pg-infected MoDCs.",
    "ncbi_link": "DC-SIGN: 30835
Mfa1: 2551415"
  },
  {
    "caption": "D) Epifluorescence microscopy images of MoDCs (si-DC-SIGN) infected with Pg381 and Mfa1+Pg. LC3-II was detected in red-fluorescent dye and the bacterial strains were pre-labeled with green CFSE.",
    "ncbi_link": "DC-SIGN: 30835
Mfa1: 2551415"
  },
  {
    "caption": "E) The figure shows the CFU counts of the P. gingivalis strains with MoDCs that lack DC-SIGN (si-DC-SIGN). The analysis of readings used One-way ANOVA analysis of different groups and Tukey's test for multiple comparisons (* p<0.001).",
    "ncbi_link": "DC-SIGN: 30835"
  },
  {
    "caption": "A) Scanning electron microscopy (SEM) of MoDCs of the early interaction of MoDCs with Pg381 and Mfa1+Pg (upper panel 10000x and lower panel 25000x). B) SEM for MoDCs interacting with Pg381 (green stains for bacteria are computer generated).",
    "ncbi_link": "Mfa1: 2551415"
  },
  {
    "caption": "C) Transmission electron microscopy (TEM) of autophagosome like structures within MoDCs infected with Pg381, Mfa1+Pg and FimA+Pg for 12 hours (upper, middle and lower panels, respectively). The right and left sections show the different magnifications of randomly selected sections. Pg381 and FimA+Pg strains are mostly enclosed in the characteristics double-membrane intracellular vesicles (Orange arrows). Contrary, Mfa1+Pg escaped these autophagic (double-membrane) vesicles and enclosed within single membrane structures or freely occupy the cytoplasm (Green arrows).",
    "ncbi_link": "Mfa1: 2551415
FimA: 2551422"
  },
  {
    "caption": "(D) Validation by western blot  of changes in specific phosphorylation  events on kinases. Left, Immunoblots  of cortical  lysates of CTL and micTNFα-KO at ZT6 for: (top) phosphorylated GSK3α/β (pGSK3α at Ser21 and pGSK3β at Ser9) and total GSK3α; and (bottom) phosphorylated MAPK  (pMAPK, MAPK3  at Thr203/Tyr205 and MAPK1  at Thr183/Tyr185) and total MAPK. Right, Ratio between phosphorylated  and total kinase normalized to CTL at ZT18 and ZT6. n=5 mice  per group. ***p=0.000009 (GSK3α), multiple t-test with Benjamini-Hochberg correction.",
    "ncbi_link": "TNFα: 21926"
  },
  {
    "caption": "(E) Kinases with altered activity between CTL and micTNF-KOs predicted by robust  kinase activity inference (RoKAI) at ZT18 and ZT6. Graph shows the z-score value of each kinase assigned by RoKAI. Kinases above and below the dotted line represent prediction of up- and downregulated activity in micTNFα-KO, respectively. Kinases are color-coded according to kinase group as described in (C).",
    "ncbi_link": "TNF: 21926
TNFα: 21926"
  },
  {
    "caption": "(F Validation by  western blot  of altered activity of predicted kinases between CTL and micTNF-KOs. (F) Left, Immunoblots  of cortical  lysates of CTL and micTNFα-KO at ZT6 using antibodies specific to target phosphorylation  motifs of MAPK/CDK  (PXS*P, S*PX(K/R)) and PKC  ((K/R)XS*X(K/R)). Dashed boxes indicate quantified signal. Right, Ratio between phosphorylated  substrates and loading control normalized to CTL at ZT18 and ZT6. (F, n=5 mice  per group. *p=0.022 (MAPK/CDK phospho  sub), *p=0.014 (PKC phospho  sub) multiple t-test with Benjamini-Hochberg correction.",
    "ncbi_link": "TNF: 21926
TNFα: 21926"
  },
  {
    "caption": "G) Validation by  western blot  of altered activity of predicted kinases between CTL and micTNF-KOs. (G) Left, Immunoblots  show signal of phosphorylated  threonine in MARKs  activation loop. Right, Ratio between phosphorylated MARK  activation loop and loading control normalized to CTL at ZT18 and ZT6. G) n=5 mice  per group. **p=0.0091 (MARK), multiple t-test with Benjamini-Hochberg correction.",
    "ncbi_link": "TNF: 21926"
  },
  {
    "caption": "C pcDNA3-based constructs expressing MAVS-Region III-dimer, trimer and tetramer were transfected into HEK293T cells respectively. ISG54 induction were measured thirty-six hours after transfection by quantitative PCR (qPCR).",
    "ncbi_link": "MAVS: 
ISG54: 3433"
  },
  {
    "caption": "F pcDNA3-FLAG-TRAF3IP3 (full-length and truncated forms) and pcDNA3-HA-MAVS were transfected into HEK293T cells, which were harvested thirty-six hours post transfection. Co-IP experiments were performed with anti-HA antibody, followed by immunoblotting.",
    "ncbi_link": "FLAG: 
HA: 
MAVS: 57506
TRAF3IP3: 80342"
  },
  {
    "caption": "G Human cells, including THP1, HeLa, HEK293, HEK293T as well as Traf3ip3-/- HEK293T, were lysed and subjected to immunoblotting to examine TRAF3IP3 expression.",
    "ncbi_link": "Traf3ip3: 80342"
  },
  {
    "caption": "A Three pairs of small interfering RNA against TRAF3IP3 were transfected into HEK293T cells respectively and immunoblotting were then employed to examine the knockdown efficiency. A pair of scrambled RNA oligoes was transfected and signified as con.",
    "ncbi_link": "TRAF3IP3: 80342"
  },
  {
    "caption": "B Three pairs of si-TRAF3IP3 together with IFNβ-luciferase reporter were transfected into HEK 293T cells. Twenty-four hours after transfection, the cells were infected with (SeV) or without (mock) Sendai virus, which were harvested six hours post infection to measure the luciferase activity.",
    "ncbi_link": "luciferase: 
IFNβ: 3456
TRAF3IP3: 80342"
  },
  {
    "caption": "C Si-TRAF3IP3 (oligo #1) were transfected into HEK 293 cells, which were then treated with mock, VSV, SeV, poly(I:C) or HSV-1. After various treatments, IFNB inductions were measured by qPCR.",
    "ncbi_link": "IFNB: 3456
TRAF3IP3: 80342"
  },
  {
    "caption": "D Immunoblotting to detect TRAF3IP3 in wild type and Traf3ip3-/- HEK293T cells.",
    "ncbi_link": "Traf3ip3: 80342"
  },
  {
    "caption": "E Wild type and Traf3ip3-/- HEK293T cells were treated with or without VSV, SeV or poly (I:C) as indicated for twelve hours. IFNB induction was measured by qPCR.",
    "ncbi_link": "IFNB: 3456
Traf3ip3: 80342"
  },
  {
    "caption": "F Wild type and Traf3ip3-/- HEK293T cells were infected with GFP-VSV. Fluorescent images were taken to examine GFP-VSV proliferation at eight hours post infection (left). Scale bar represents 10 micrometers. GFP-VSV titers were quantitated by plaque assay (right).",
    "ncbi_link": "GFP: 
Traf3ip3: 80342"
  },
  {
    "caption": "G Various expression constructs were transfected into WT and Traf3ip3-/- HEK293T cells. Thirty-six hours after transfection, IFNB induction was measured by qPCR.",
    "ncbi_link": "IFNB: 3456
Traf3ip3: 80342"
  },
  {
    "caption": "H Mavs-/- HEK293T cells were transfected with empty vector, pcDNA-FLAG-MAVS, pcDNA-FLAG-MAVS-(Region III only), or pcDNA-FLAG-MAVS-(ΔRegion III), together with pcDNA3-FLAG-TRAF3IP3 or not as indicated. Twenty-four hours after transfection, cells were infected with SeV for twelve hours. IFNB induction was measured by qPCR.",
    "ncbi_link": "FLAG: 
IFNB: 3456
Mavs: 57506
MAVS: 57506
TRAF3IP3: 80342"
  },
  {
    "caption": "A The experiment was performed as described in Fig 2C. Instead of IFNB, ISG54 and IL6 inductions were measured by qPCR.",
    "ncbi_link": "ISG54: 3433
IFNB: 3456
IL6: 3569"
  },
  {
    "caption": "B HEK293 cells were transfected with si-TRAF3IP3 oligos and then treated with various stimuli. Following subcellular fractionation, S5 fractions were obtained and subjected to native PAGE for detecting IRF3 dimer by immunoblotting. The whole cell lysates were also subjected to SDS-PAGE for anti- IRF3 and tubulin immunoblotting.",
    "ncbi_link": "TRAF3IP3: 80342"
  },
  {
    "caption": "C The experiment was performed as described in Fig 2E. ISG54 and IL6 induction was measured by qPCR.",
    "ncbi_link": "ISG54: 3433
IL6: 3569"
  },
  {
    "caption": "D Wild type and Traf3ip3-/- HEK293T cells were infected with or without VSV. At indicated time points, Cells were collected and analyzed by immunoblotting. Following subcellular fractionation, S5 fractions were subjected to native PAGE to examine IRF3 dimer, and P5 fractions contained mitochondria were subjected to SDD-AGE to examine MAVS aggregation. The mitochondrial outer membrane protein Prohibitin was immunoblotted as an internal control.",
    "ncbi_link": "Traf3ip3: 80342"
  },
  {
    "caption": "A pcDNA-FLAG-TRADD and pcDNA-FLAG-TRAF3IP3 were transfected into HEK293T cells at increasing amount respectively. ISG54 and IL6 induction were measured thirty-six hours post-transfection by qPCR. Expression levels were shown in Fig EV4B. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05, **P<0.01 and ***P<0.001 NS indicates no statistically significant difference.",
    "ncbi_link": "FLAG: 
ISG54: 3433
IL6: 3569
TRADD: 8717
TRAF3IP3: 80342"
  },
  {
    "caption": "B HEK293T cells were transfected with pcDNA3-HA-TRAF3IP3, in combination with pcDNA3-FLAG- RIG-I, MAVS, TBK1, IRF3, TRAF2, TRAF3, TRAF5, or TRAF6 as indicated. Thirty-six hours after transfection, cells were collected and anti-HA immunoprecipitations were performed. IP products were subjected to immunoblotting.",
    "ncbi_link": "FLAG: 
HA: 
RIG-I: 23586
IRF3: 3661
MAVS: 57506
TBK1: 29110
TRAF2: 7186
TRAF3: 7187
TRAF3IP3: 80342
TRAF5: 7188
TRAF6: 7189"
  },
  {
    "caption": "C shRNA targeting TRAF3IP3 (sh-TRAF3IP3) was transduced into Mavs-/- HEK293T cells. Twenty-four hours after transduction, cells were treated with puromycin (2 μg/mL) for forty-eight hours and then transfected with pcDNA3-FLAG-MAVS-(Region III only). Twenty-four hours after transfection, cells were infected with or without VSV for twelve hours. Cells were then collected and subjected to immunoprecipitation assay and immunoblotting.",
    "ncbi_link": "FLAG: 
Mavs: 57506
MAVS: 57506
TRAF3IP3: 80342"
  },
  {
    "caption": "D Wild type and Traf3ip3-/- HEK293T cells were transfected with pcDNA3-FLAG-MAVS-(Region III only). Twenty-four hours post-transfection, cells were infected with or without VSV. Twelve hours post-infection, cells were collected and subjected to immunoprecipitation assay and immunoblotting.",
    "ncbi_link": "FLAG: 
MAVS: 57506
Traf3ip3: 80342"
  },
  {
    "caption": "C-E Immunofluorescent microscopic imaging for TRAF3IP3. HeLa cells were transfected with pcDNA3-FLAG-TRAF3IP3. Twenty-four hours after transfection, cells were infected with or without SeV for twelve hours. Anti-FLAG M2 (FITC) was used for immunofluorescence staining of FLAG-TRAF3IP3. Nuclei were stained with DAPI. Mitochondria was stained with Mitotracker Red (C). Calnexin (an ER protein) was stained for ER (D). GM130 (a Golgi protein) was stained for Golgi (E). Scale bar represents 5 micrometers. F Quantitative analysis of yellow color as shown in Fig 5C, D and E, indicating TRAF3IP3 localization on various organelles with or without virus infection. The quantification was performed with ImageJ. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. ***P<0.001. NS indicates no statistically significant difference.",
    "ncbi_link": "FLAG: 
TRAF3IP3: 80342"
  },
  {
    "caption": "BMDMs from wild type, Traf3ip3-/- and Mavs-/- mice were treated with or without VSV, SeV, poly (I:C) or HSV-1 respectively as indicated for six hours. Ifnb (A), Ifna4 (B), Il6 induction was measured respectively by qPCR. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference.",
    "ncbi_link": "Ifna4: 15967
Ifnb: 15977
Il6: 16193
Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "BMDMs from wild type, Traf3ip3-/- and Mavs-/- mice were treated with or without VSV, SeV, poly (I:C) or HSV-1 respectively as indicated for six hours. Il6 (C), Isg54 (D), and Cxcl10 (E) induction was measured respectively by qPCR. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference.",
    "ncbi_link": "Cxcl10: 15945
Isg54: 15958
Il6: 16193
Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "F BMDMs from wild type, Traf3ip3-/- and Mavs-/- mice were infected with or without VSV for six hours. Cells were then collected and following subcellular fractionation, S5 fractions were subjected to native PAGE to examine IRF3 dimer, and P5 fractions contained mitochondria were subjected to SDD-AGE to examine MAVS aggregation.",
    "ncbi_link": "Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "Wild type, Traf3ip3-/- and Mavs-/- mice (three littermates per group) were infected intravenously with VSV at a MOI of 2×108. The spleens were collected 4 hours or 8 hours after infection and Ifna4 (A), Ifnb (B), Isg54 (C) and Il6 (D) inductions were measured respectively by qPCR. All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference.",
    "ncbi_link": "Isg54: 15958
Ifna4: 15967
Ifnb: 15977
Il6: 16193
Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "Wild type, Traf3ip3-/- and Mavs-/- mice (three littermates per group) were infected intravenously with VSV at a MOI of 2×108. The spleens were collected 4 hours or 8 hours after infection and VSV RNA levels were measured by qPCR (E). All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference.",
    "ncbi_link": "Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "Wild type, Traf3ip3-/- and Mavs-/- mice (three littermates per group) were infected intravenously with VSV at a MOI of 2×108. The sera were collected from the treated mice and used for the measurement of IFNβ production by ELISA (F). All data are presented as the mean values based on three independent experiments, and error bars indicate s.d. P values were determined by unpaired two-tailed Student's t-test. *P<0.05 and **P<0.01. NS indicates no statistically significant difference.",
    "ncbi_link": "Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "G Wild type, Traf3ip3-/- and Mavs-/- mice (n=6 each) were injected with VSV via tail vein injection at 5×107 pfu per mouse, and the survival rates were monitored for 15 days. P values were determined by unpaired two-tailed Student's t-test. *P<0.05",
    "ncbi_link": "Mavs: 228607
Traf3ip3: 215243"
  },
  {
    "caption": "(C) qPCR  quantification of  ssc-miR-205 and bta-miR-10b miRNAs in murine  (M.m.), porcine (S.s.), and  bovine (B.t.) oocytes, respectively. Shown are a mean values from three independent experiments. Error bars = SD. Detailed information concerning miRNA quantification is provided in the Methods section.",
    "ncbi_link": "miR-10b: 791051
miR-205: 100316607"
  },
  {
    "caption": "(A) bta-miR-10b and  ssc-miR-205 miRNAs efficiently repress microinjected NanoLuc luciferase reporters carrying a perfectly complementary (1x perfect) miRNA binding site or four partially complementary (bulged) miRNA binding sites. Error bars = SD. Each data point represents a value obtained from five microinjected oocytes. Data were collected in two microinjection sessions, each microinjection session used a new batch of in vitro transcribed reporter mRNAs. Data information: asterisks indicate statistical significance (p-value) of one-tailed t-test, (*p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "Luc: 
miR-10b: 791051
miR-205: 100316607"
  },
  {
    "caption": "(B) De-repression of predicted  ssc-miR-205 targets. In three independent microinjection experiments, ssc-miR-205  was inhibited by a microinjected antisense oligonucleotide inhibitor and target levels were assessed 24 hours after microinjection by  RT-qPCR. Error bars = SD. Data information: asterisks indicate statistical significance (p-value) of one-tailed t-test, (*p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "miR-205: 100316607"
  },
  {
    "caption": "(C) Inhibition of  ssc-miR-205 by a microinjected antisense oligonucleotide inhibitor results in reduced development to the blastocyst stage. Shown is development of microinjected oocytes to the blastocyst  stage relative to water-injected oocytes. Five independent experiments (represented by individual data points) were performed, ~50 porcine oocytes were microinjected in each group in each experiment. Difference between let-7a and miR-205 inhibitors effects is statistically significant (two-tailed paired t-test p-value = 0.016). Error bars = SD. Data information: asterisks indicate statistical significance (p-value) of one-tailed t-test, (*p < 0.05, **p < 0.01, ***p < 0.001).",
    "ncbi_link": "miR-205: 100316607
let-7a: 100498702"
  },
  {
    "caption": "(A) ssc-miR-205  turnover. Fully-grown transcriptionally quiescent oocytes were cultured for indicated periods of time  and selected miRNAs were quantified by RT-qPCR in four (ssc-let-7a), five (ssc-miR-22) or six (ssc-mir10b and ssc-miR-205) independent experiments. Error bars = SD.",
    "ncbi_link": "mir10b: 100498711
miR-205: 100316607
miR-22: 100498778
let-7a: 100498702"
  },
  {
    "caption": "(B) Comparison of mean relative changes of miRNA level at 20 h of culture ssc-miR-205 in oocytes is less than ssc-miR-10b, ssc-miR-22, or ssc-let-7a. Error bars = SD. Asterisks indicate statistical significance (p-value) of one-tailed paired t-test, (*p < 0.05, **p < 0.01).",
    "ncbi_link": "miR-10b: 100498711
miR-205: 100316607
miR-22: 100498778
let-7a: 100498702"
  },
  {
    "caption": "(C) Treatment by sodium periodate followed by qPCR does not support 2'-OH modification of either ssc-miR-205  or  bta-miR-10b miRNA. Shown are relative levels of the  sodium periodate-treated samples to non-treated samples, which were set to one. The experiment was performed three times. Error bars = SD. Efficiency of  periodate treatment was confirmed using non-methylated and methylated miR-221  RNA  oligonucleotides",
    "ncbi_link": "miR-221: 
miR-10b: 791051
miR-205: 100316607"
  },
  {
    "caption": "G, HBMEC were transiently transfected with control siRNA or PI3K p110α siRNA. Cells expressing either control siRNA or PI3K p110α siRNA were challenged with T. gondii 48 h after transfection. Cell lysates were subject to immunoblotting as indicated. Densitometry data are shown as above and represent means ± SEM of 3 experiments. Results shown are representative of 3-4 independent experiments.",
    "ncbi_link": "PI3K p110α: 5290"
  },
  {
    "caption": "B, HBMEC were transfected with control siRNA or Akt siRNA. Cells were then challenged with T. gondii 48 h after transfection. Monolayers were examined microscopically 24 h post-challenge.",
    "ncbi_link": "Akt: 207"
  },
  {
    "caption": "G, H, mHEVc cells were transfected with Beclin 1 siRNA (G), Atg7 siRNA (H) or control siRNA. After 48 h, cells were treated with or without Akt inhibitor IV for 1 h prior to challenge with T. gondii. Monolayers were examined by light microscopy at 24 h.",
    "ncbi_link": "Atg7: 74244
Beclin 1: 56208"
  },
  {
    "caption": "B, HBMEC were transfected with MyD88 siRNA or control siRNA followed by challenge with T gondii after 48 h. Cell lysates were used to examine total Akt and phospho-serine 473 Akt by immunoblot. Results shown are representative of 3 independent experiments.",
    "ncbi_link": "MyD88: 4615"
  },
  {
    "caption": "A, mHEVc cells were transfected with control siRNA or EGFR siRNA. Expression of EGFR and actin were assessed by immunoblot 48 h post-transfection. mHEVc cells expressing either control siRNA or EGFR siRNA were challenged with T. gondii. Cell lysates were used to examine the expression total Akt or phospho-Ser473 Akt by immunoblot.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "B, Mouse microglia were treated with or without AG1478 (1 µM) 1 h prior to challenge with T. gondii. Cell lysates were used to examine the expression total Akt or phospho-Ser473 Akt by immunoblot. Densitometry data represent means ± SEM of 3 experiments. A vertical line was inserted between densitometry data from control siRNA and EGFR siRNA or control and AG1478-treated cells to indicate that band densities from infected control cells or infected cells subjected to EGFR blockade were compared to bands from their respective uninfected cells, which were given an arbitrary number of 1. Results shown are representative of 3 independent experiments.",
    "ncbi_link": "EGFR: 13649"
  },
  {
    "caption": "B, Human RPE cells transfected with either EGFR or control siRNA were challenged with T. gondii followed by examination of monolayers by light microscopy at 24 h.",
    "ncbi_link": "EGFR: 1956"
  },
  {
    "caption": "D, Parental CHO and CHO-EGFR cells were challenged with RH T. gondii. Monolayers were examined microscopically 2 h or 24 h post-challenge.",
    "ncbi_link": "EGFR: 100774580"
  },
  {
    "caption": "G, H, mHEVc cells transfected with Beclin1 siRNA (G) or Atg7 siRNA (H) were transfected with EGFR siRNA or treated with or without AG1478 followed by challenge with T. gondii. Monolayers were examined by light microscopy 24 h post-challenge. Results are shown as the mean ± SEM and are representative of 3 independent experiments.",
    "ncbi_link": "Atg7: 74244
Beclin1: 56208
EGFR: 13649"
  },
  {
    "caption": "A, B, C HBMEC were challenged with ΔHx (WT), MIC1 ko, MIC3 ko, MIC1-3 ko T. gondii at MOIs that yielded similar percentages of infected cells (A).",
    "ncbi_link": "MIC1: 7896467
MIC3: 7901253"
  },
  {
    "caption": ". C, hmCD40 mHEVc-LC3-EGFP cells were treated with or without CD154 followed by challenged with WT, MIC1 ko, MIC1 ko+MIC1, MIC3 ko, MIC3 ko+MIC3, MIC1-3 ko, MIC1-3 ko+MIC1-3 tachyzoites. LC3 accumulation around the parasite was examined by fluorescence microscopy 5 h post-challenge. D, hmCD40 mHEVc-LC3-EGFP treated with or without CD154 were challenged with WT, MIC1 ko, MIC1 ko+MIC1, MIC3 ko, MIC3 ko+MIC3, MIC1-3 ko or MIC1-3 ko+MIC1-3 tachyzoites. Parasite load was examined 24 h post-challenge.",
    "ncbi_link": "MIC1: 7896467
MIC3: 7901253"
  },
  {
    "caption": "E, HBMEC cells were challenged with WT, MIC1 ko, MIC3 ko, MIC1-3 ko tachyzoites followed by treatment with vehicle or rapamycin. Parasite load was examined 24 h post-challenge. F, HBMEC treated with or without CD154 or IFN-γ/TNF-α were challenged with WT, MIC1 ko, MIC3 ko, MIC1-3 ko tachyzoites. Monolayers were examined microscopically at 24 h post-challenge.",
    "ncbi_link": "MIC1: 7896467
MIC3: 7901253"
  },
  {
    "caption": "G, hmCD40 mHEVc cells treated with or without CD154 were infected with either WT or MIC1-3 ko tachyzoites in the presence of complete medium (CM) alone or medium plus MIC3, MIC4, M2AP or MIC6 (all 10 nM). Parasite load was determined microscopically 24 h post challenge. Results shown are representative of 3-4 independent experiments.",
    "ncbi_link": "MIC1: 7896467"
  },
  {
    "caption": "Western blot analysis of the recombinant RPB1 expression (rWT, YFFF, and ∆5) assessed by (HA)-tag expression after 24 or 48 hours of α-amanitin treatment following 24h of induction. Untransfected Raji extracts are shown for comparison (WT). Total RPB1 levels are represented by the F12 western blot. Tubulin was used as a loading control.",
    "ncbi_link": "RPB1: 5430"
  },
  {
    "caption": "Example of ChrRNA read-through phenotype at the 5' (anti-sense) and 3' (sense) ends in CTD-∆5 at the GBE1 locus.",
    "ncbi_link": "GBE1: 2632"
  },
  {
    "caption": "(D) qPCR validation of TH levels in SN samples of PD and controls, normalized to beta-actin mRNA. T-test p*=0.025, Data presented as mean ± SD. n=18 for CT and 24 for PD.",
    "ncbi_link": "beta-actin: 60
TH: 7054"
  },
  {
    "caption": "(E) Adar1 expression levels in all tissues. The box is drawn from Q1 to Q3 with a horizontal line drawn in the middle to denote the median and x marks the average. Whiskers mark minimum or maximum values.",
    "ncbi_link": "Adar1: 103"
  },
  {
    "caption": "(H) Volcano plot of DE circRNAs in PD vs control tissues, red dots indicate statistically significant DE circRNAs according to FDR correction of Wald test (DEseq2 analysis). CircSLC8A1 is marked is red.",
    "ncbi_link": "CircSLC8A1: "
  },
  {
    "caption": "(B, C) CircSLC8A1 and linear SLC8A1 levels in the SN of control and PD brains, T-test p=0.025, p= 0.118 respectively.",
    "ncbi_link": "CircSLC8A1: 
SLC8A1: 6546"
  },
  {
    "caption": "(D) qPCR validations of circSLC8A1 and SLC8A1 mRNA changes in the SN, T-test p*=0.025. n=18 for CT and 24 for PD, x defines mean values.",
    "ncbi_link": "circSLC8A1: 
SLC8A1: 6546"
  },
  {
    "caption": "(E) no difference in circSLC8A1 levels in females and males, T-test p=0.583 for control and p=0.262 for PD. n=15 females and 16 males. . The box is drawn from Q1 to Q3 with a horizontal line drawn in the middle to denote the median and x marks the average.",
    "ncbi_link": "circSLC8A1: "
  },
  {
    "caption": "(F, G) CircSLC8A1 and linear SLC8A1 mRNA levels are correlated in control, R2=0.47 T-test p=0.0017 but not in PD samples, R2= 0.016, p>0.05. n=18 for CT and 23 for PD.",
    "ncbi_link": "CircSLC8A1: 
SLC8A1: 6546"
  },
  {
    "caption": "(H) Increased CircSLC8A1 RNA levels in PQ-exposed SH-SY cells (normalized to Tubb3 and RPL19) while other circRNAs remain unchanged",
    "ncbi_link": "CircSLC8A1: 
RPL19: 6143
Tubb3: 10381"
  },
  {
    "caption": "(A) qPCR measurements of circSLC8A1 and SLC8A1 mRNA after SH-SY treatment of statins or the PF LRRK2 inhibitor, T-test p**=0.007 and p**=0.01 for PF-06447475 and p*=0.047 and p=*0.0136 for Statins for cirSLC8A1 and SLC8A1 mRNA respectively",
    "ncbi_link": "circSLC8A1: 
cirSLC8A1: 
SLC8A1: 6546"
  },
  {
    "caption": "(B) qPCR quantification from nuclear/cytoplasmic fractionations of SH-SY cells, T-test p=0.005 for circSLC8A1, p=0.009 for NEAT1 and p=0.009 for Rpl19. n=3 biological replicas for each condition.",
    "ncbi_link": "circSLC8A1: 
NEAT1: 283131
Rpl19: 6143"
  },
  {
    "caption": "(C) qPCR quantification of Ago2-bound RNA, immunoprecipitated (IP)/Input values normalized to negative control for a known Ago2 target, circCDR1as and circSLC8A1, T-test p=0.029 for circSLC8A1 and p=0.001 for circCDR1as, n=3 biological replicas for each condition.",
    "ncbi_link": "circCDR1: 
circSLC8A1: "
  },
  {
    "caption": "(G) relative expression of known miR-128 targets from SN RNA-seq, p**=0.0004 for BMI1, p*=0.011 for SIRT1 and p*=0.005 for AXIN1.",
    "ncbi_link": "AXIN1: 8312
BMI1: 648
miR-128: 406916///406915
SIRT1: 23411"
  },
  {
    "caption": "(H) relative expression of known miR-128 targets in SH-SY cells treated with Paraquat, T-test p*=0.03, p*=0.02 and p*=0.002 for AXIN1, BM1 and SIRT1 respectively, Data presented as mean ± SD with 4-6 biological replicas for each condition.",
    "ncbi_link": "AXIN1: 8312
BM1: 648
miR-128: 406916///406915
SIRT1: 23411"
  },
  {
    "caption": "Luciferase-based imaging of drug response in Vegfr3Luc;Tyr:CreERT2;BrafV600E; Ptenflox/flox mice. Panels labeled as \"basal\" and \"induced\" correspond to the bioluminescence of animals prior and 5 weeks after administration of 4OH-tamoxifen (5 mM, topical administration, 3 consecutive days) for the induction of melanomas. (Right panels) Treatment with anti-PD-L1 antibody (αPD-L1; clone 10F.9G2, 3 weeks) or the corresponding control IgG (200 ug/dose, twice per week, 3 weeks); vemurafenib (Vem, 50 mg/Kg, oral once per day, 3 weeks) or BO-110 (BO, 0.8 mg/kg, twice per week, 3 weeks). Scale: p/s/cm2/sr (x106).",
    "ncbi_link": "Luc: 
Braf: 109880
Cre: 2777477
Vegfr3: 14257
ERT2: 26417
Pten: 19211"
  },
  {
    "caption": "Treatment with BO-110 of human patient-derived xenografts (PDX) implanted in Vegfr3Luc nu/nu. 42 days after implantation (when systemic luciferase was detected), animals were randomized for treatment with vehicle (V) or with 0.8 mg/kg BO-110 (BO, twice per week), and luciferase emission was acquired at the indicated  times. Scale, p/s/cm2/sr (x106).",
    "ncbi_link": "Luc: 
Vegfr3: 14257"
  },
  {
    "caption": "qRT-PCR analysis of relative mRNA levels of MDA5 16 h after treatment of HLEC with 0.5 ug/ml  BO-110 (BO), 10 µM vemurafenib  (Vem), or vehicle control (V). Data correspond to the mean ± SD of 3 biological replicates. Statistical significance was determined by t-test.   qRT-PCR analysis of relative mRNA levels of VEGFR3 16 h after treatment of HLEC with 0.5 or 1 ug/ml BO-110 (VO), 10 µM vemurafenib (Vem), or the corresponding vehicle control (V). Data correspond to the mean ± SD of 3 biological replicates. Statistical significance was determined by ANOVA.   ",
    "ncbi_link": "VEGFR3: 2324
MDA5: 64135"
  },
  {
    "caption": "Luciferase signal driven by FLT4 (VEGFR3)-promoter transduced into HLEC treated with vehicle (v) or BO-110 (BO) at the indicated doses (ug/ml) as indicated in methods. Results were normalized to vehicle control. N=4 biological replicates. Error bars correspond to mean ± SD. Statistical significance was determined by ANOVA.",
    "ncbi_link": "Luciferase: 
FLT4: 2324
VEGFR3: 2324"
  },
  {
    "caption": "Relative mRNA levels of VEGFC  and VEGFD in the indicated melanoma cell lines 8 h after treatment with vehicle (V) or 0.5 µg/ml BO-110 (BO), as determined by qRT-PCR. Data correspond to the mean ± SD of 3 experiments. Statistical significance was determined by t-test.",
    "ncbi_link": "VEGFC: 7424
VEGFD: 2277"
  },
  {
    "caption": "Inhibitory effect of the indicated doses of BO-110 (in µg/ml) or vehicle (V) on MDK mRNA  expression  determined by qRT-PCR in SK-Mel-147 (16 h after treatment). Data correspond to average mRNA levels in three experiments with technical replicates normalized to vehicle control ± SD. Statistical significance was determined by ANOVA.   qRT-PCR  analysis of relative mRNA levels of MDA5 16 h after treatment of SK-Mel-147 with the indicated doses of BO-110 (in µg/ml) (BO). Data correspond to the mean ± SD of three experiments with three technical replicates. Statistical significance was determined by ANOVA.   ",
    "ncbi_link": "MDA5: 64135
MDK: 4192"
  },
  {
    "caption": "Type I IFN mRNA induction (IFNA2 and IFNB1) in SK-Mel-147 melanoma cells treated for 16 h with the indicated amounts of BO-110 (in mg/ml). Data correspond to the mean ± SD of three experiments with three technical replicates normalized to vehicle control. Statistical significance was determined by ANOVA.",
    "ncbi_link": "IFNA2: 3440
IFNB1: 3456"
  },
  {
    "caption": "Heatmap depicting expression changes in interferon-related genes (GO:0034340) in SK-Mel-147 melanoma cells (left panel) and HLEC (right panel) treated with vehicle or 0.5 g/ml of BO-110 for 10 hours.  CD274, LAG3 and PDCD1 genes were also included as a reference.",
    "ncbi_link": "CD274: 29126
LAG3: 3902
PDCD1: 5133"
  },
  {
    "caption": "IFNB1  mRNA induction analyzed by qPCR at the indicated times  after BO-110 treatment (0.5 µg/ml) of SK-Mel-147 melanoma cells or HLEC (left and right graphs, respectively). Data correspond to the mean ± SD of three experiments with three technical replicates normalized to vehicle control.",
    "ncbi_link": "IFNB1: 3456"
  },
  {
    "caption": "Quantification of the impact of  BO-110 as single agent or in the presence of the indicated blocking antibodies for type I interferon (IFNB1 or IFNAR1). Upper graphs show the effect of these agents on  MDK mRNA levels in SK-Mel-147 melanoma cells. Similar treatments were performed on HLEC for the analysis of VEGFR3  mRNA (middle graphs) and tube formation capacity (lower graphs). Data correspond to the mean ± SD of 3 biological replicates in triplicate.",
    "ncbi_link": "VEGFR3: 2324
MDK: 4192"
  },
  {
    "caption": "Growth  of B16 melanoma xenografts in siblings of  Ifnar1+/+, Ifnar1+/- or Ifnar1-/- mice. Treatment started 10 days after tumor cell implantation. BO-110 was administered at 0.8 mg/kg, every third day for 2 weeks. N= 6 mice per condition. Graphs show the mean tumor size ± SD at each time point. Statistical significance was determined by Two-Way ANOVA.",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "(C) Western blot  and quantitative analysis for the expression  of TFAM  in HCC  cells with TFAM  stable knockdown and control cells (n = 3 independent experiments). shCtrl, control shRNA; shTFAM, shRNA against TFAM; EV, empty vector; TFAM, expression vector encoding TFAM. Data information: Graphs show mean ± s.e.m., two-tailed unpaired t-test. **P < 0.01.",
    "ncbi_link": "TFAM: 7019"
  },
  {
    "caption": "(E) The level of malonylated mDia2. Equal amount of immunoprecipitated mDia2  either from TFAM knockdown or control cells was loaded in Western blot  assay.",
    "ncbi_link": "TFAM: 7019"
  },
  {
    "caption": "(B) mRNA level of TFAM  in 50 HCC patients' paired tissues from TCGA database. The relative expression  ratio of tumor to non-tumor was log2-transformed.",
    "ncbi_link": "TFAM: 7019"
  },
  {
    "caption": "(E) RNAi of representative Atg genes decreased the LTR fluorescence levels compared with control. (Atg1, P = 0.01; Atg5, P = 0.01; Atg7, P = 0.002; Atg8a, P = 0.008; Atg8b, P = 0.006; and Atg12, P = 0.02).",
    "ncbi_link": "Atg1: 39454
Atg12: 39383
Atg5: 31666
Atg7: 37141
Atg8a: 32001
Atg8b: 42132"
  },
  {
    "caption": "(F) RNAi of all tested genes in the TOR-PI3K pathways had a statistically significant effect on LTG fluorescence levels. Known negative regulators of autophagy are shown with gray bars; positive regulators are shown with white bars. (Pten, P = 0.007; Tsc1, P = 0.027; Tsc2, P = 0.025; RheB, P = 0.005; Tor, P = 0.016; and S6k, P = 0.012). dsRNA corresponding to a human gene (Hs) was used as a negative control in E and F. Results represent the mean value ± SD from at least three independent experiments.",
    "ncbi_link": "Hs: 
Tsc2: 40201
Pten: 43991
RheB: 117332
S6k: 38654
Tor: 47396
Tsc1: 42862"
  },
  {
    "caption": "(A) The percentage of LTGhigh cells was reduced by hid-RNAi (P = 0.006) but not by rpr, grim, and skl-RNAi.",
    "ncbi_link": "grim: 40014
rpr: 40015
skl: 40016
hid: 31271"
  },
  {
    "caption": "(B) Knockdown of Ras, phl, and rl expression by RNAi resulted in an increase in the percentage of LTGhigh cells. (Ras, P = 0.003; phl, P = 0.001; and rl, P = 0.028).",
    "ncbi_link": "phl: 31221
Ras: 38494///41140
rl: 3354888"
  },
  {
    "caption": "(C) th-RNAi treatment (24 h) had no significant effect on LTG levels; in contrast, RNAi of Bruce resulted in an increase in LTG fluorescence levels (P = 0.01).",
    "ncbi_link": "Bruce: 41260
th: 39753"
  },
  {
    "caption": "(D) Reduction of debcl, Buffy, or p53 expression by RNAi resulted in a decrease in LTG fluorescence levels. (debcl, P = 0.018; Buffy, P = 0.006; and p53, P = 0.004).",
    "ncbi_link": "Buffy: 36251
debcl: 53585
p53: 2768677"
  },
  {
    "caption": "(E) RNAi of effector caspase Dcp-1 resulted in a significant decrease in the LTGhigh population (P = 0.001).",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(G) Quantification of cells with GFP-LC3 puncta after RNAi treatment. Cells with more than three GFP-LC3 punctate dots were considered to be GFP-LC3-positive cells. Cells treated with the RNAi indicated here all showed a significant difference (P < 0.05) in the percentage of GFP-LC3-positive cells compared with the human (Hs) RNAi control. (Pten, P = 0.006; Tor, P = 0.034; Buffy, P = 0.005; debcl, P = 0.003; Bruce, P = 0.003; Dcp-1, P = 0.007; hid, P = 0.002; Ras, P = 0.006; and phl, P = 0.050). Results represent the mean value ± SD from three independent experiments.",
    "ncbi_link": "Bruce: 41260
Buffy: 36251
Dcp-1: 37729
debcl: 53585
Hs: 9020
phl: 31221
Pten: 43991
Ras: 38494///41140
Tor: 47396
hid: 31271"
  },
  {
    "caption": "(A) GFP-LC3 proteins were expressed in nurse cells (NC) but not in follicle cells (FC) by using the UASp/nanos Gal4 system. DAPI staining of nuclei is shown in blue.",
    "ncbi_link": "nanos: 42297"
  },
  {
    "caption": "(B) UASp-GFP-LC3; nanos GAL4 flies were conditioned on yeast paste and had a diffuse GFP-LC3 pattern. Numerous GFP-LC3 puncta (green) at region 2 within germarium were observed in nutrient-deprived flies. Ovaries were stained with LTR in w1118 flies. Germarium of nutrient-deprived w1118 flies had an increase in punctate LTR staining (red) compared with well-fed germarium.",
    "ncbi_link": "nanos: 42297"
  },
  {
    "caption": "(A) Germaria of the nutrient-deprived Dcp-1Prev flies showed a dramatic decrease in LTR staining compared with nutrient-deprived wild-type flies shown in Fig. 3 B. DAPI staining of nuclei is shown in blue. (B) Degenerating stage 8 egg chambers (arrows) of nutrient-deprived Dcp-1Prev flies showed a dramatic decrease in LTR staining compared with nutrient-deprived wild-type flies shown in Fig. 3 C.",
    "ncbi_link": "Dcp-1: 37729"
  },
  {
    "caption": "(C) Lack of Dcp-1 function (UASp-GFP-LC3 Dcp-1Prev/Dcp-1Prev; nanos-GAL4/+) resulted in uniform diffuse staining of GFP-LC3 rather than the punctate pattern observed in wild-type degenerating stage 8 egg chambers shown in Fig 3 C. (D) Dying egg chambers (arrows) of NGT/+; nanos-GAL4/UASp-fl-Dcp-1 flies that were conditioned on yeast paste showed a significant increase in punctate LTR staining (red) compared with healthy egg chambers (arrowheads). (E) Expression of activated Dcp-1 (a truncated form) and GFP-LC3 in the germ line (UASp-GFP-LC3/+; nanos-GAL4/nanos-GAL4 UASp-tDcp-1) resulted in abundant degenerating stage 8 egg chambers (arrows) with numerous GFP-LC3 puncta (green). DAPI staining of nuclei is shown in blue.",
    "ncbi_link": "Dcp-1: 37729
nanos: 42297"
  },
  {
    "caption": "(A) The germarium in well-fed BruceE81 flies showed an increase in LTR staining (red) compared with wild-type well-fed flies shown in Fig. 3 B (top right). DAPI staining (white) of nuclei is shown on the right. (B) In well-fed wild-type flies, mid-oogenesis nurse cell death is a rare event. Lack of Bruce function resulted in an increase in dying stage 8 egg chambers (arrows) in ovaries under well-fed conditions, and these degenerating stage 8 egg chambers had numerous LTR (red) punctate dots. DAPI staining (white) is shown on the right. Bars: (A) 20 μm; (B) 50 μm.",
    "ncbi_link": "Bruce: 41260"
  },
  {
    "caption": "(A) Ovaries were stained with TUNEL (green) to detect DNA fragmentation. Clusters of cysts with TUNEL staining were observed in region 2 in nutrient-deprived w1118 files. In Dcp-1Prev flies, fewer TUNEL-positive cysts in region 2 were observed. Under well-fed conditions, numerous TUNEL-positive cysts were observed in BruceE81 flies. DAPI staining of nuclei is shown in white. (B) Numerous degenerating stage 8 egg chambers (arrows) with Bruce-positive staining (green) were observed in well-fed BruceE81 flies. DAPI staining of nuclei (white) is shown on the right.",
    "ncbi_link": "Bruce: 41260
Dcp-1: 37729"
  },
  {
    "caption": "(A) TUNEL-positive staining was observed in dying stage 8 egg chambers (arrows) of starved control flies (CG5335d30/Atg7d14). DAPI staining of nuclei (white) is shown on the right. (B) In nutrient-deprived Atg7 mutants (Atg7d77/Atg7d14), degenerating stage 8 egg chambers (arrows) showed no or low levels of TUNEL staining. Nuclear DNA condensation, detected by DAPI, was still observed. (C) Dying stage 8 egg chambers (arrows) from nutrient-deprived control siblings (Atg1Δ3D/TM3) generated from the same cross in D had abundant TUNEL-positive staining. (D) In nutrient-deprived Atg1 GLCs, degenerating stage 8 egg chambers (arrows) showed no or low levels of TUNEL staining. Nuclear DNA condensation (DAPI, right) in degenerating egg chambers appeared to occur as in the controls.",
    "ncbi_link": "Atg1: 39454
Atg7: 37141"
  },
  {
    "caption": "(D, E) (D) Western blot analysis confirming lack of PIDD1 expression in A549 cells and (E) MDM2 processing after induction of cytokinesis failure using ZM (2µM) for 48h. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0. 1 (*), p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "PIDD1: 55367"
  },
  {
    "caption": "(F) Live-cell imaging analysis of NF-κB EGFP-reporter activity in CRISPR-edited polyclonal A549κB cells. NF-κB activity of ZM-treated cells is represented as fold-change with respect their untreated counterparts (DMSO-treated cells, grey lines). n=5 independent experiments. Error bars represent ± SEM. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0. 1 (*), p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(H) Live-cell imaging analysis of NF-κB EGFP-reporter activity in CRISPR-edited polyclonal RPE1kB cells analyzed as in as in F. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0. 1 (*), p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "CRISPR: "
  },
  {
    "caption": "(C) Left, representative immunofluorescence images of supernumerary centrosomes originated from Dox-inducible PLK4 overexpression in CRISPR-edited polyclonal U2OSPLK4 cells. Size scale bar: 10µm. Right, representative cell cycle profiles of U2OSPLK4 control and PIDD1-deficient cells. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "CRISPR: 
PIDD1: 55367
PLK4: 10733"
  },
  {
    "caption": "(E) Live-cell imaging analysis of NF-κB EGFP-reporter activity in CRISPR-edited polyclonal PIDD1-competent or -deficient U2OSκB-PLK4 and A549κB-PLK4 cells. NF-κB activity of ZM, Dox or TNF-treated cells is represented as fold-change with respect to their untreated counterparts. Bars represent means of n=5 independent experiments ± SEM. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "CRISPR: 
PIDD1: 55367
PLK4: 10733"
  },
  {
    "caption": "(F) Representative immunofluorescence images of A549 cells co-stained with the indicated antibodies and documenting PIDD1 localization at centrosomes. Scale bars: 10 μm. (G) Luciferase reporter analysis of NF-κB activity in CRISPR-edited SCLT1- competent or -deficient A549 cells. Luciferase activity was normalized respect renilla control. n=3 independent experiments; represented mean values ± SEM. Data information: The statistical significance was determined using two-way ANOVA; p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "CRISPR: 
SCLT1: 132320"
  },
  {
    "caption": "(B) Left, immunoblot of CRISPR-edited polyclonal RIPK1- or NEMO-deficient A549κB derivatives. Right, luciferase assay of A549 cells indicated genotypes, treated for 48h with either ZM (2 μM) or DHCB (4 μM). n=4 independent experiments. Data are represented as the mean values ± SEM. The statistical significance was determined using two-way ANOVA; p< 0.01 (**);p< 0.001 (***); p< 0.0001 (****).",
    "ncbi_link": "CRISPR: 
NEMO: 8517
RIPK1: 8737"
  },
  {
    "caption": "(D) Different time point immunoprecipitations (IP) after release in ZM (2 μM) of endogenous RAIDD, RIPK1 and NEMO proteins in PIDD1-deficient 293T-Trex-Flip-in cells re-expressing a FLAG-tagged PIDD1-FL protein. One representative experiment out of three is shown.",
    "ncbi_link": "PIDD1: 55367"
  },
  {
    "caption": "(E) Analysis of NEMO-PIDDosome formation in PIDD1-deficient 293Trex-Flip-In cells re-expressing different PIDD1 mutants depicted in G. Cells were treated as in C and processed for FLAG-IP 11h after release into DMSO or ZM (2 μM). One out of two independent experiments is shown.",
    "ncbi_link": "PIDD1: 55367"
  },
  {
    "caption": "(F) 293T cells were transiently transfected with constructs allowing expression of GFP, a full length (FL) single (PIDD1-FL_FLAG) or double-tagged (HA_PIDD1-FL_FLAG) version of PIDD1, or an HA-tagged N-terminal fragment of PIDD1 (HA_PIDD1-N). Co-immunoprecipitation was performed to probe for interaction with endogenous RIPK1 after either anti-FLAG or anti-HA pull-down. One out of two independent experiments is shown.",
    "ncbi_link": "FLAG: 
GFP: 
HA: 
PIDD1: 55367"
  },
  {
    "caption": "Primary MEF from Pidd1-/- mice were treated for 72h with ZM or DMSO and subjected to mRNA-sequencing analysis. (B) qRT-PCR analysis confirm expression of different pro-inflammatory genes in Pidd1+/+ but not Pidd1-/- MEF. Hprt1, β-actin and Gapdh were used as housekeeping gene expression controls. n=3 independent samples; data represent mean values ± SEM. The statistical significance was determined using two-way ANOVA test; p ≤ 0.01 (**), p ≤ 0.001 (***).",
    "ncbi_link": "β-actin: 11461
Gapdh: 14433
Hprt1: 15452
Pidd1: 57913"
  },
  {
    "caption": "Primary MEF from Pidd1-/- mice were treated for 72h with ZM or DMSO and subjected to mRNA-sequencing analysis. (D) qRT-qPCR analysis of macrophage activation markers indicative of a pro-inflammatory state. Relative expression values are plotted as the fold-change expression relative to BMDM stimulated with conditioned medium from untreated MEFPLK4. β-actin was used as housekeeping gene for normalization. Bars represent mean ± SEM (n=9) biological replicates. The statistical significance was determined using two-way ANOVA; p ≤ 0. 1 (*), p ≤ 0.01 (**), p ≤ 0.001 (***), p ≤ 0.0001 (****).",
    "ncbi_link": "β-actin: 11461
Pidd1: 57913
PLK4: 20873"
  },
  {
    "caption": "A549EGFP cells were treated with DMSO or ZM (2μM) for 72h, followed by co-culture with NK-92 cells and live-cell imaging analysis. (D) Confluence of ZM pre-treated A549EGFP cells expressing or lacking PIDD1 was measured over time in presence of NK cells and normalized with respect to their DMSO treated counterparts. Middle, NK cell-mediated killing interpolated from cell confluence graphs at 50 h. n≥4 independent experiments performed in duplicates, mean ± SEM. (E) Confluence measurement over time of A549EGFP derivatives impaired in either NEMO-PIDDosome (RIPK1 KO) or Caspase-2-PIDDosome formation (RAIDD KO). Middle, NK cell-mediated killing interpolated from cell confluence graphs at 50 h. n≥3 independent experiments; mean ± SEM; unpaired t-test. (F) Confluence analysis of Dox pre-treated A549EGFP cells overexpressing PLK4 was performed over time in the presence of NK cells and normalized with respect to their DMSO treated controls. n=5 independent experiments; mean ± SEM. (G) Confluence analysis of centriole-depleted and ZM pre-treated A549EGFP cells cultured in presence of NK cells. Values are normalized with respect to their DMSO ± Centrinone (125nM) treated controls. n=4 independent experiments; mean ± SEM. Data information: The statistical significance was determined using two-tailed t-test; P < 0.001 (**); P < 0.001 (***).",
    "ncbi_link": "RAIDD: 8738
PIDD1: 55367
PLK4: 10733
RIPK1: 8737"
  },
  {
    "caption": "Luc-CTL assay was performed with MCF7 cells transfected with control or PD-L1-specific siRNAs and cocultured with or without CTLs and bsAb. For each condition, the luciferase activity of PD-L1-siRNA-treated cells was normalized to that of the control siRNA; n = 8. Error bars denote ± SEM.",
    "ncbi_link": "PD-L1: 29126"
  },
  {
    "caption": "C-E Graphical summary of gene function related to modification of T cell-mediated tumor lysis and cellviability for screens 1, 2, and 3, respectively. Positive score = reduced cancer cellviability; negative score = increased viability. X-axis: influence on cellviability without addition of T cells. Y-axis: influence on cellviability with addition of T cells. Appropriate immune-suppressive (PD-L1, CEACAM-6, GAL-3) and lethality (UBC, PLK-1) controls, along with few positive (GRM4, GRK5) and negative (CCR9, IL8) candidate immune-modulatory hits are highlighted herein.",
    "ncbi_link": "CCR9: 10803
PD-L1: 29126
CEACAM-6: 4680
IL8: 3576
GRK5: 2869
GRM4: 2914
GAL-3: 3958
PLK-1: 5347
UBC: 7316"
  },
  {
    "caption": "C-E Graphical summary of gene function related to modification of T cell-mediated tumor lysis and cellviability for screens 1, 2, and 3, respectively. Positive score = reduced cancer cellviability; negative score = increased viability. X-axis: influence on cellviability without addition of T cells. Y-axis: influence on cellviability with addition of T cells. Appropriate immune-suppressive (PD-L1, CEACAM-6, GAL-3) and lethality (UBC, PLK-1) controls, along with few positive (GRM4, GRK5) and negative (CCR9, IL8) candidate immune-modulatory hits are highlighted herein.",
    "ncbi_link": "CCR9: 10803
PD-L1: 29126
CEACAM-6: 4680
IL8: 3576
GRK5: 2869
GRM4: 2914
GAL-3: 3958
PLK-1: 5347
UBC: 7316"
  },
  {
    "caption": "A MCF7 cells were transfected with the described siRNA sequences and harvested after 72 h for mRNA and protein estimation using RT-PCR (upper) and immunoblot (lower) analysis, respectively. GAPDH and beta-actin were used as controls for RNA and protein normalization, respectively.",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "B Luc-CTL cytotoxicity assay with PBMC-derived CTLs and bi-specific Ab as effector population and MCF7 as target cells, which were transfected with individual (s1-s4) or pooled CCR9 siRNA sequences. PD-L1 and non-specific control siRNAs were used as positive and negative controls, respectively, for CTL-mediated cytotoxicity.",
    "ncbi_link": "CCR9: 10803
PD-L1: 29126"
  },
  {
    "caption": "C, D Cr-release assay showing % specific lysis of MCF7 cells by survivin-specific T cells at different ratios upon CCR9 knockdown (C) or overexpression (D). MCF7 cells were transfected with either CCR9 siRNA s1 (Δ), pooled siRNA sequences (○), positive control PD-L1 (□), and non-specific control siRNA (▪) (C) or with pCMV6-AC-His control vector (▪) and pCMV6-AC-His-CCR9 expression construct (○) (D) 72 h prior to the assay.",
    "ncbi_link": "CCR9: 10803
PD-L1: 29126"
  },
  {
    "caption": "E Cr-release assay showing % specific lysis of MDA-MB-231 breast tumor cell line by survivin-specific T cells at different ratios upon CCR9 knockdown (○) in comparison to the control knockdown (▪).",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "F, G Cr-release assay showing lysis of patient-derived melanoma cells (M579-A2) by tumor-infiltrating lymphocytes (TIL 412) (F) or lysis of PANC-1 pancreatic adenocarcinoma cells by patient-derived pancreatic TIL 53 (G) at different E:T ratios upon CCR9 (○) or control (▪) knockdown.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "A, B ELISpot assay showing IFN-γ (A) and granzyme B (B) secretion by survivin-specific T cells, as spot numbers, upon CCR9 knockdown (black bars) in MCF7 cells compared to the control knockdown (white bars). T cells (TC) alone (grey bars) were used as control for background spot numbers.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "C Luminex assay showing cytokine levels in the supernatant from the coculture of survivin-specific TC and either CCR9hi MCF7 (transfected with CCR9-specific siRNA) or CCR9lo MCF7 (transfected with control siRNA) cells.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "D Phospho-plex analysis showing the phospho-STAT levels in survivin-specific TC upon encountering CCR9hi or CCR9lo MCF7 cells. Log2 ratio of mean fluorescent intensity (MFI) of the respective analytes to the unstimulated TC is plotted herein.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "E Immunoblot analysis showing the phospho-STAT1 levels in the CCR9hi-treated, CCR9lo-treated or unstimulated TC using the phospho-specific STAT1 (pTyr701) antibody. Beta-actin was used as the loading control.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "A ELISA showing CCL25 levels in cell lysates from indicated tumorcell lines. CCR9 knockdown (k.d.) in MCF7 cells was achieved using specific shRNA (see Materials and Methods).",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "B Cr-release assay showing % specific lysis of MCF7 cells by survivin TC upon CCL25 (□) or CCR9 (○) inhibition using specific siRNAs in comparison to the control siRNA (▪). Mean ± SEM are depicted herein.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "C MCF7 cells were transfected with control or CCR9-specific siRNAs, and 48 h later, the supernatants (CCR9lo or CCR9hi SSN, respectively) were used to culture survivin TCs overnight. Supernatant-treated TCs were then used as effector cells against CCR9lo or CCR9hi MCF7 tumor cells in the Cr-release assay along with wild-type MCF7 cells. Mean ± SEM are depicted herein.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "D Cr-release assay showing % specific lysis of MCF7 cells that were pre-treated with or without pertussis toxin (PTX), or knocked down for CCR9 using specific siRNA. Mean ± SEM are depicted herein.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "E, F MCF7 cells transfected with control siRNA (CCR9hi) or CCR9 siRNA (CCR9lo) were cocultured with survivin TCs for 12 h. Gene microarray was performed with the total RNA extracted from purified T cells after the coculture. Volcano plot (E) illustrating fold change (FC; log2) in gene expression intensities compared with P-value (−log2) between CCR9hi- and CCR9lo-treated TCs. Horizontal bar at y = 4.32 represents a statistical significance of P = 0.05 (genes in gray below this line did not reach significance). LogFC cutoff at ± 0.5 is represented by the vertical lines. Heatmap representation of the top upregulated (LogFC > 0.5) and downregulated (LogFC < −0.85) genes (F) with P ≤ 0.05. Individual replicates per sample group are shown herein.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "A Cr-release assay showing TIL 209-mediated lysis of CCR9+ M579-A2 (transduced with control shRNA) or CCR9− M579-A2 cells (transduced with CCR9-specific shRNA). Curves represent mean ± SEM.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "C, D Tumorgrowth curves showing mean ± SEMtumor volume of CCR9+ or CCR9−M579-A2tumors in TIL-treated mice (C) or the PBS alone group (D). Statistical difference was calculated using the unpaired one-sided Mann-Whitney U-test.",
    "ncbi_link": "CCR9: 10803"
  },
  {
    "caption": "b and c. Representation and quantification of cell length in epidermal (e) and cortical (c) cell files. Optical, longitudinal sections of 5 DAG eir1-4 roots 12 HAT to ammonium (B) or nitrate (C) supplemented media. The first 20-20 epidermal and cortex cells (from quiescent center (QC)) are highlighted in grey and in red on ammonium (B) and in blue and green on nitrate (C), respectively. Scale bar=30 µm. Column bars denote the geometric mean of cell length at the respective positions. Lines represent a polynomial regression fit, with calculated slopes between cells 10 and 20 of 0.75884+0.02624 (ammonium, epidermis), 1.13088+0.08446 (ammonium, cortex) and 2.06912+0.10341 (nitrate, epidermis), 0.99878+0.07278 (nitrate, cortex). Data are derived from 3 biological replicates, n=9 (ammonium) and 8 (nitrate) roots.",
    "ncbi_link": "eir1: 835813"
  },
  {
    "caption": "b. Higher magnification of pseudo-colored confocal images of 5 DAG old roots expressing PIN2-GFP 12 HAT to ammonium or nitrate supplemented media. \"e\" denotes epidermis and \"c\" cortex, respectively. Color code represents GFP intensity from low (blue) to high (white) values. Scale bar=12 µm. White stars mark PIN2-GFP protein localization on the lateral membranes. Box plots display lateralization index (fluorescent signal detected on apical/basal membranes divided by the signal value at inner/outer membranes) of roots on ammonium (n=31 cells from 6 roots) or nitrate (n=24 cells from 6 roots) supplemented medium. The statistical significance was evaluated with ANOVA at p<0.05. The box chart components are defined as; box (25%-75%), central band (median line), central box (mean) and the range is within 1.5IQR.",
    "ncbi_link": "GFP: 
PIN2: 835813"
  },
  {
    "caption": "d. Microscopic images showing PIN2-Dendra fluorescent signal five hours after photoconversion of PIN2-Dendra into its red form. Depletion of the red signal and recovery of the green signal over a 6 hours period was followed in parallel in 5 DAG old roots12 HAT to ammonium or nitrate supplemented media. Note the increase in the intensity of the green signal in roots transferred to nitrate. Graph represents the mean signal + SD (n=6 roots per condition, 20 cells per root analyzed). The experiment was repeated 3 times. Scale bar=20 µm.",
    "ncbi_link": "Dendra: 
PIN2: 835813"
  },
  {
    "caption": "g. Box plots display lateralization index (fluorescent signal detected on apical/basal membranes vs inner/outer membranes) of P2wt, P2D and P2A roots transferred to ammonium (grey) or nitrate (red) supplemented medium. At least 24 cells from 5 roots were analyzed per genotype per treatment. The statistical significance was evaluated with ANOVA at p<0.05. The box chart components are defined as; box (25%-75%), central band (median line), central box (mean) and the range is within 1.5IQR.",
    "ncbi_link": "P2: 835813"
  },
  {
    "caption": "U2OS EJ5-GFP cells were transfected with the indicated siRNAs. At 24hr post-transfection, cells were transfected with the I-SceI expression plasmid, and the GFP+ population was analyzed 48 hr post-plasmid transfection. The percentage of GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition (siCTRL).",
    "ncbi_link": "I-SceI: "
  },
  {
    "caption": "Quantification of the Neutral Comet assay. U2OS cells stably expressing shCtrl, shREV7 or shSHLD2 were exposed to IR (10 Gy) and run in low melting agarose under neutral conditions. Immunofluorescence against DNA stained with SYBR Gold was performed to measure the tail moment.",
    "ncbi_link": "REV7: 10459
SHLD2: 54537"
  },
  {
    "caption": "U2OS cells stably expressing HA-REV7 (Top) or HA-SHLD2 (Bottom) were pre-sensitized with 10ug/mL Hoescht 33342 before exposed to UV micro-irradiation. Immunofluorescence against endogenous HA and γ-H2AX epitope was subsequently performed to monitor REV7 and SHLD2 accumulation at sites of damage. Shown are representative micrographs. Scale bar = 5µm.",
    "ncbi_link": "HA: 
REV7: 10459
SHLD2: 54537"
  },
  {
    "caption": "U2OS LacR-Fok1 cells were transfected with GFP or GFP-SHLD2 and 24 h later DNA damage was induced using Shield-1 and 4-OHT. The cells were then processed for GFP and mCherry immunofluorescence. Shown are representative micrographs. Scale bar = 5µm. Quantification of the experiments shown in (C). Data are represented as the mean ± SD (n=3). At least 100 cells per condition were counted.",
    "ncbi_link": "Fok1: 
GFP: 
LacR: 
SHLD2: 54537"
  },
  {
    "caption": "Quantification of the experiments shown in (C). Shown is the quantification of the GFP signal at the mCherry-LacR-Fok1 focus.",
    "ncbi_link": "Fok1: 
LacR: 
mCherry: "
  },
  {
    "caption": "293T cell lines expressing ER-AsiSI with Flag-SHLD2 and treated with 1 µM of 4-OHT. 6h later the cells were processed and immunoprecipitated with Anti-FLAG Magnetic Beads and anti-γ-H2AX.x/Protein A/G magnetic beads. DNA was purified and subjected to qPCR detection. Shown is the quantification of IP efficiency as the percentage of DNA precipitated from input (Bottom).",
    "ncbi_link": "AsiSI: 
Flag: 
SHLD2: 54537"
  },
  {
    "caption": "U2OS cells stably expressing HA-SHLD2∆720-904 (Left) or HA-SHLD2∆1-680 (Right) were processed as in (B). Immunofluorescence against endogenous HA and RPA32 epitope was subsequently performed to monitor RPA32 and SHLD2 accumulation at sites of damage. Shown are representative micrographs. Scale bar = 5µm.",
    "ncbi_link": "HA: 
SHLD2: 54537"
  },
  {
    "caption": "U2OS mCherry-LacR-Fok1 cells were treated with the indicated siRNA and subsequently transfected with a GFP-SHLD2 construct. 24 h post-transfection DNA damage was induced using Shield-1 and 4-OHT. The cells were then fixed and analyzed for the intensity of the GFP-SHLD2 signal at mCherry-LacR-Fok1 focus. Shown is the quantification of the GFP-SHLD2 signal at the Fok1 focus. Data are represented as a box-and-whisker plot where the whiskers represent the 10-90 percentile. At least 75 cells were counted per condition.",
    "ncbi_link": "Fok1: 
GFP: 
LacR: 
mCherry: 
SHLD2: 54537"
  },
  {
    "caption": "293T cells were transfected with Flag-REV7 and GFP-SHLD2 expression vectors as indicated. 24h post-transfection cells were treated with DMSO or with 10uM of ATM inhibitor KU-60019 for 1 h prior to irradiation. 1h post-irradiation (10 Gy) nuclear extracts were prepared and REV7 complexes were immunoprecipitated using anti-Flag (M2) Resin and then analyzed by immunoblotting using GFP, REV7 and p-Chk1 antibodies.",
    "ncbi_link": "Flag: 
GFP: 
REV7: 10459
SHLD2: 54537"
  },
  {
    "caption": "U2OS EJ5-GFP cells were transfected with the indicated siRNAs. At 24hr post-transfection, cells were transfected with the I-SceI expression plasmid, and the GFP+ population was analyzed 48 hr post-plasmid transfection. The percentage of GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition (siCTRL).",
    "ncbi_link": "GFP: 
I-SceI: "
  },
  {
    "caption": "U2OS DR-GFP cells were transfected with the indicated siRNAs. At 24hr post-transfection, cells were transfected with the I-SceI expression plasmid, and the GFP+ population was analyzed 48 hr post-plasmid transfection. The percentage of GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition (siCTRL).",
    "ncbi_link": "GFP: 
I-SceI: "
  },
  {
    "caption": "293T cells were transfected with Flag-REV7 and GFP-SHLD1 (Left) or Flag-SHLD2 and GFP-SHLD1 (Right) expression vectors as indicated. 24h post-transfection cells were treated with DMSO or with 10uM of ATM inhibitor KU-60019 for 1 h prior to irradiation. 1h post-irradiation (10 Gy) nuclear extracts were prepared and REV7 or SHLD2 complexes were immunoprecipitated using anti-Flag (M2) Resin and then analyzed by immunoblotting using GFP and REV7 antibodies.",
    "ncbi_link": "Flag: 
GFP: 
REV7: 10459
SHLD1: 149840
SHLD2: 54537"
  },
  {
    "caption": "U2OS EJ5-GFP cells were transfected with either siCTRL, siSHLD1 #1 or siSHLD1 #2. At 24hr post-transfection, cells were transfected with the I-SceI expression plasmid, and the GFP+ population was analyzed 48 hr post-plasmid transfection. The percentage of GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition (siCTRL).",
    "ncbi_link": "GFP: 
I-SceI: 
SHLD1: 149840"
  },
  {
    "caption": "CH12F3-2 cells stably expressing either shCTRL, shSHLD1#1 or shSHLD1#2 were stimulated with a cocktail of cytokines (CIT) to induce class switching to IgA. The percentage of IgA+ cells was monitored 24 and 48h post-stimulation by staining with an anti-IgA antibody followed by flow cytometry analysis.",
    "ncbi_link": "SHLD1: 73747"
  },
  {
    "caption": "U2OS DR-GFP cells were transfected with the indicated siRNAs. At 24hr post-transfection, cells were transfected with the I-SceI expression plasmid, and the GFP+ population was analyzed 48 hr post-plasmid transfection. The percentage of GFP+ cells was determined for each individual condition and subsequently normalized to the non-targeting condition (siCTRL).",
    "ncbi_link": "GFP: 
I-SceI: "
  },
  {
    "caption": "A-O UAS.RNAi lines were driven with eyeless.Gal4gmr.Gal4 for expression during eye development or nubbin-Gal4 for expression during wing development. (A, B) Control adult Drosophilaeye (A) and wing (B). (C, D) α-spectrin RNAi results in overgrowth of the eye (C) and wing (D). (E, F) βH-spectrin/karst RNAi results in overgrowth of the eye (E) and wing (F). (G, H) β-spectrin RNAi does not affect eye size (G) or wing size (H). (I, J) kibra RNAi results in overgrowth of the eye (I) and wing (J). (K, L) α-spectrin, kibra double RNAi results in stronger overgrowth of the eye (K) and wing (L). (M, N) βH-spectrin/wing, kibra double RNAi results in stronger overgrowth of the eye (M) and wing (N). (O) Quantification of female wing sizes by pixel area, 5 wings per genotype were measured. Error bars show standard deviation.P-RThe eyeless FLP MARCM system was used to generate clonally mutant flyeyes. eyes mutant eyes (Q) overgrow slightly compared to controls (P), while α-spectrin mutant eyes expressing α-spectrin RNAi (R) overgrow strongly compared to controls (P).Data information: Scale bars, 250 μm.",
    "ncbi_link": "Gal4: 
gmr: 
nubbin: 
α-spectrin: 38231
kibra: 41783
karst: 38418
β-spectrin: 38418
βH-spectrin: 38418"
  },
  {
    "caption": "A-F The eyeless FLP MARCM system was used to generate mutant eyes that also express UAS.RNAi targeting the Spectrin cytoskeleton. Pupalretinas were examined at 42-46 h after puparium formation (APF). Cellmembranes were marked with Dlg staining. (A) Control pupalretina showing cone cells surrounded by interommatidial cells. (B) kibra mutant pupalretina displaying additional interommatidial cells. (C) Pupalretina expressing α-spectrin RNAi showing additional interommatidial cells. (D) kibra mutant pupalretinas expressing α-spectrin RNAi showing many additional interommatidial cells. (E, F) Clones of α-spectrin mutant cells (GFP negative) (E) and βH-spectrin/karst mutant cells (GFP negative) (F) show extra interommatidial cells. Scale bars, 20 μm.",
    "ncbi_link": "UAS: 
α-spectrin: 38231
kibra: 41783
karst: 38418
βH-spectrin: 38418"
  },
  {
    "caption": "G-K UAS.RNAi lines were driven with hh.Gal4 UAS.GFP for expression in the posterior compartment and contained the ex.lacZ reporter transgene. (G) Control wing showing a normal ex.lacZ expression pattern, which is low at the dorsal-ventral boundary but high in the proximal regions of the wing disc. (H) RNAi knock-down of α-Spectrin results in a mild up-regulation of ex.lacZ in the posterior compartment. (I) RNAi knock-down of kibra results in a mild up-regulation of ex.lacZ in the posterior compartment. (J) Dual RNAi knock-down of both α-spectrin and kibra results in enhanced up-regulation of ex.lacZ in the posterior compartment. (K) RNAi knock-down of hippo results in an up-regulation of ex.lacZ in the posterior compartment. Scale bars, 50 μm.",
    "ncbi_link": "Gal4: 
lacZ: 
UAS: 
α-Spectrin: 38231
α-spectrin: 38231
kibra: 41783"
  },
  {
    "caption": "D Control nubbin.Gal4 expressing wing.E Overexpression of Ex activates Hippo signalling to produce a small wing.F RNAi knock-down of α-Spectrin results in an overgrown wing.G Overexpression of Ex blocks the effect of α-Spectrin RNAi.H RNAi knock-down of βH-spectrin/karst results in an overgrown wing.I Overexpression of Ex blocks the effect of βH-spectrin/karst RNAi.",
    "ncbi_link": "Gal4: 
nubbin: 
α-Spectrin: 38231
Ex: 33218
Hippo: 37247
karst: 38418
βH-spectrin: 38418"
  },
  {
    "caption": "The apical α-βHSpectrincytoskeleton may be mechanosensory in the wing imaginal discA Schematic diagram of central compression and circumferencial stretching in the third instarwing pouch.B-D Third instarwing imaginal disc stained for beta-galactosidase expressed from the expanded.lacZ reporter gene (B), Crb (C) and Kst-YFP (D). Quantification of line intensity shown below. Note inverse correlation of Crb and Kst-YFP with ex.lacZ. Scale bars, 50 μm.E, F Zoom of Kst-YFP cells under compression (E) and under stretch (F). Scale bars, 10 μm.G Schematic diagram of the effect of force on the apical spectrin cytoskeleton leading to declustering of Crumbs complexes and reduced Hippo signalling.",
    "ncbi_link": "lacZ: 
Crb: 42896
expanded: 33218
Kst: 38418"
  },
  {
    "caption": "B Control nub.Gal4 wing.C, D Expression of UAS.CrbExTM-GFP with Gal4.Gal4 (C) or UAS.Wts with nub.Gal4 (D) results in a small wing.E RNAi knock-down of α-Spectrin results in an overgrown wing.F, G Expression of UAS.CrbExTM-GFP (F) or UAS.Wts (G) blocks the effect of α-Spectrin RNAi.H RNAi knock-down of βH-spectrin/karst results in an overgrown wing.I, J Expression of UAS.CrbExTM-GFP (I) or UAS.Wts (J) blocks the effect of α-Spectrin RNAi.K, L RNAi knock-down of Wts results in a strongly overgrown wing (K) and expression of UAS.CrbExTM-GFP does not block the effect of wts RNAi (L).M, N RNAi knock-down of Ajuba results in a small wing (M), and expression of UAS.CrbExTM-GFP enhances the effect of ajuba RNAi (N).O Quantification of various wing sizes. Error bars show standard deviation.",
    "ncbi_link": "Gal4: 
GFP: 
nub: 
UAS: 
α-Spectrin: 38231
Crb: 42896
ajuba: 32351
Ajuba: 32351
karst: 38418
βH-spectrin: 38418"
  },
  {
    "caption": "A Control egg chamber stained for DAPI to mark nuclei.B Overexpression of Yki3SA stimulates follicle cell proliferation (MARCM clone, GFP positive).C-F Mutation of βH-spectrin/karst (C) or crb (D) does not increase follicle cell proliferation (GFP negative clone), while mutation of α-spectrin (E) or β-spectrin (F) stimulates follicle cell proliferation (GFP negative clone).",
    "ncbi_link": "α-spectrin: 38231
crb: 42896
karst: 38418
β-spectrin: 38418
βH-spectrin: 38418
Yki: 37851"
  },
  {
    "caption": "G Control egg chamber stained for Cut, a marker of proliferating cells that is normally down-regulated after stage 6 of oogenesis.H-K Mutation of βH-spectrin/karst (H) or crb (I) does not increase Cut expression in follicle cells (GFP negative clone), while mutation of α-spectrin (J) or β-spectrin (K) stimulates Cut expression in posterior follicle cells (GFP negative clone).L Control egg chamber showing ex.lacZ reporter gene expression.M-P Mutation of βH-spectrin/karst (M) or crb (N) does not increase ex.lacZ expression in follicle cells (GFP negative clone), while mutation of α-spectrin (O) or β-spectrin (P) stimulates ex.lacZ expression in posterior follicle cells (GFP negative clone).",
    "ncbi_link": "lacZ: 
α-spectrin: 38231
crb: 42896
karst: 38418
β-spectrin: 38418
βH-spectrin: 38418"
  },
  {
    "caption": "Q Wild-type follicle cells showing normal hexagonal packing of epithelial membranes.R Mutation of β-spectrin disrupts the normal hexagonal packing, suggesting a role in maintaining membrane tension.S Clone of β-spectrin mutant cells (GFP negative) showing differential membrane tension at the interface with wild-type cells (GFP positive).",
    "ncbi_link": "β-spectrin: 38418"
  },
  {
    "caption": "Basolateralα-β Spectrins are required to restrict cellproliferation in theDrosophila intestinal epitheliumA Control myo1A.Gal4UAS.GFP adult midgut stained for phospho-histone H3 to mark mitotic stem cells.B-E RNAi knock-down of βH-spectrin/karst (B) or crumbs (C) does not increase stem cellproliferation, while RNAi knock-down of β-spectrin (D) or α-spectrin (E) strongly stimulates stem cellproliferation.F Overexpression of Yki strongly stimulates stem cellproliferation.G Quantification of the number of PH3-positive mitotic cells. N > 13 samples. Statistical analysis performed using the two-tailed Student's t-test. Error bars show standard deviation. ***P-value ≤ 0.001.H-K A Hippo reporter DIAP1-HRE-GFP is normally expressed in sporadic stem cells. Its expression is not affected by RNAi knock-down of βH-spectrin/karst (I), but is up-regulated in many stem cells by RNAi knock-down of α-spectrin (J) or by overexpression of Yki (K).Data information: Scale bars, 100 μm.",
    "ncbi_link": "Gal4: 
HRE: 
myo1A: 
UAS: 
α-spectrin: 38231
crumbs: 42896
Hippo: 37247
karst: 38418
β-spectrin: 38418
βH-spectrin: 38418
Yki: 37851"
  },
  {
    "caption": "A Control Caco-2 epithelial cells plated a low density show strong nuclear YAP localisation.B Control Caco-2 epithelial cells plated at high density show relocalisation of YAP to the cytoplasm.C, D siRNA knock-down of SPTAN1 (C) or SPTBN1 (D) prevents relocalisation of YAP to the cytoplasm.",
    "ncbi_link": "SPTAN1: 6709
SPTBN1: 6711"
  },
  {
    "caption": "F Western blotting reveals that SPTAN1 or SPTBN1 are required for normal levels of YAP phosphorylation, and of LATS1 phosphorylation.",
    "ncbi_link": "SPTAN1: 6709
SPTBN1: 6711"
  },
  {
    "caption": "G siRNAs against SPTAN1 or SPTBN1 efficiently deplete their target proteins.",
    "ncbi_link": "SPTAN1: 6709
SPTBN1: 6711"
  },
  {
    "caption": "OTULIN DNA sequence chromatograms showing the homozygous single base substitution (c.841G>A, p.Gly281Arg, arrowhead). Data are representative to two independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Immunoblot analysis of IκBα phosphorylation and degradation as well as p65/RelA phosphorylation in healthy control or OTULING281R fibroblasts primary fibroblasts in response to stimulation with TNF (10 ng/mL). Data are representative of three independent experiments. Immunoblot analysis of phosphorylation of the MAP kinases p38 and JNK in healthy control or OTULING281R primary fibroblasts in response to stimulation with TNF (10 ng/mL). Data are representative of three independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "ELISA analysis of IL-8 secretion in response to TNF stimulation (10 ng/mL) in healthy control or OTULING281R primary fibroblasts. Bars represent mean ± SEM (n=4).",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Immunoblot analysis of the native TNF-RSC purified by immunoprecipitation from healthy control or OTULING281R primary fibroblasts. Data are representative of three independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Immunoblot analysis of whole cell lysate from untreated human THP-1 monocytes with stable expression of a non-targeting control shRNA or and shRNA targeting OTULIN. Data are representative of two independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Immunoblot (left) and densitometry (right) analysis of IκBα levels in shControl and shOTULIN THP-1 cells treated with cycloheximide (CHX) (50 μg/mL) as indicated. Data are representative of three independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "ELISA analysis of spontaneous TNF secretion over 96 h in shControl and shOTULIN THP-1 cells. Data represents mean ± SEM (n=4) and were analysed using the two-way ANOVA test of statistical significance with Sidak's correction for multiple comparisons.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Immunoblot analysis of IκBα phosphorylation and degradation as well as p65/RelA phosphorylation in shControl and shOTULIN THP-1 cells in response to stimulation with TNF (10 ng/mL). Data are representative of three independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Viability of healthy control or OTULING281R primary fibroblasts after 24 h and 6 h, respectively, of treatment with TNF (100 ng/mL), CHX (50 μg/mL), as indicated was analysed using MTT reduction assays.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Viability of healthy control or OTULING281R primary fibroblasts after 24 h and 6 h, respectively, of treatment with TNF (100 ng/mL), CHX (50 μg/mL), Q-VD-OPh (10 μM), and Nec-1 (10 μM) as indicated was analysed using MTT reduction assays.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "Viability of shControl and shOTULIN THP-1 cells (C-D) after 24 h and 6 h, respectively, of treatment with TNF (100 ng/mL), CHX (50 μg/mL),",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "shControl and shOTULIN THP-1 cells (C-D) after 24 h and 6 h, respectively, of treatment with TNF (100 ng/mL), CHX (50 μg/mL), Q-VD-OPh (10 μM), and Nec-1 (10 μM) as indicated was analysed using MTT reduction assays.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "C Telo-PCR analysis of telomere length in wt (ter1+ and est1+) and two independent clones (a and b) deleted for ter1+ or est1+ grown for ~ 25+10 (~ 35), ~ 25+14 (~ 39) and ~ 25+18 (~ 43) pds in YES medium. PCRs were performed with the subtelomeric oligonucleotide oF5, located 620 bp upstream of the first telomeric repeat, and the oligo(dG)-containing oligonucleotide odG18. Marker (m) molecular weights are on the left in kilobases. tels: telomere-containing Telo-PCR products.",
    "ncbi_link": "est1: 2540492
ter1: 9407016"
  },
  {
    "caption": "D qRT-PCR analysis of G-rich TERRA, polyA+ TERRA and ARRET/αARRET levels in cells as in (B). Values are normalized to ACT1 mRNA and expressed as fold increase over control wt strains (ter1+ and est1+) grown in parallel. Bars and error bars are averages and SD from 4 (ter1Δ clones) or 3 (est1Δ clones) independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001 (relative to wt; two-tailed Student's t test).",
    "ncbi_link": "ACT1: 
ARRET: 
TERRA: 
est1: 2540492
ter1: 9407016"
  },
  {
    "caption": "E ChIP experiments with anti-RNA polymerase II (RPII) antibodies and extracts from ter1+ and ter1Δ cells grown for ~ 43 pds. Quantitative PCRs were performed using oligonucleotides oF1 + oR1 (subtel) or oligonucleotides amplifying a region from the actively transcribed act1+ locus. Values are expressed as fold increase over ter1+. Bars and error bars are averages and SD from three independent experiments. * P < 0.05 (relative to ter1+; two-tailed Student's t test). The western blot to the right shows no difference in RNPII levels between ter1+ and ter1Δ cells used in ChIP experiments. Ponceau Sstaining serves as loading control.",
    "ncbi_link": "act1: 
ter1: 9407016"
  },
  {
    "caption": "G Western blot analysis of cellular fractions from ter1+ and ter1Δ cells grown for ~ 43 pds. Total proteins (tot) and equivalents of soluble (sol) and insoluble (ins) proteins were loaded. Actin serves as a control for soluble proteins, H3K9ac for chromatin-bound proteins.",
    "ncbi_link": "ter1: 9407016"
  },
  {
    "caption": "H qRT-PCR analysis of total TERRA and polyA+ TERRA in cellular fractions as in (G). Values are expressed after normalization to total cellular extracts. Bars and error bars are averages and SD from 3 independent experiments.",
    "ncbi_link": "TERRA: "
  },
  {
    "caption": "A RIP experiments were performed using anti-myc antibodies and extracts from Trt1-myc expressing strains followed by qRT-PCR to detect G-rich TERRA, polyA+ TERRA, ARRET, TER1 and ACT1. Values represent fractions of input RNA detected in immunoprecipitated material expressed as fold increase over untagged (unt) wt strain. Bars and error bars are averages and SD from three independent experiments. * P < 0.05 (relative to unt; two-tailed Student's t test).",
    "ncbi_link": "ACT1: 
ARRET: 
TER1: 
TERRA: 
Trt1: 2540601"
  },
  {
    "caption": "B RIP experiments as in (A) where, prior to RNA extraction, washed beads were resuspended in DNaseI buffer (DNbuff) and incubated for 1 hour at 30° C in presence or absence of DNaseI. Values represent fractions of input polyA+ TERRA detected in immunoprecipitated material expressed as fold increase over an untagged (unt) wt strain. Bars and error bars are averages and SD from three independent experiments. * P < 0.05 (relative to unt; two-tailed Student's t test).",
    "ncbi_link": "TERRA: "
  },
  {
    "caption": "C RIP experiments were performed using anti-myc antibodies and extracts from Trt1-myc expressing strains (either ter1+ or ter1Δ) cultured in YES medium for ~ 43 pds. Values represent polyA+ TERRA detected in immunoprecipitated material expressed as a fraction of the input (graph on the left) or after normalization to ACT1 RNA in the corresponding input (on the right), and expressed as fold increase over an untagged wt strain (unt ter1+). Bars and error bars are averages and SD from three independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001 (relative to unt ter1+; two-tailed Student's t test).",
    "ncbi_link": "ACT1: 
TERRA: 
ter1: 9407016
Trt1: 2540601"
  },
  {
    "caption": "D Western blot analysis of Trt1-myc in cells used in (C). Ponceau S staining serves as a loading control.",
    "ncbi_link": "Trt1: 2540601"
  },
  {
    "caption": "B Genomic DNA from wt cells (CAF13) and cells carrying two tiTELs (CAF110) maintained in YES medium was digested with HindIII and Southern blot-hybridized consecutively with the indicated probes. RET refers to telomeric sequences (tiTELs or natural telomeres, nTELs) retained in the upper part of the gel; REL refers to telomeric sequences released in the lower part of the gel. The black arrow points to the natural nmt1+ sequence on chromosome III. Marker molecular weights are on the left in kilobases.",
    "ncbi_link": "nmt1: 2539108"
  },
  {
    "caption": "D qRT-PCR analysis of tiTERRA in cells carrying no tiTEL (CAF13), one tiTEL (CAF545) or two tiTELs (CAF110) cultured in EMM medium in presence or absence of Thiamine (THI; repressed and induced condition, respectively) for 24 h. RNA was reverse transcribed with oC and cDNA was amplified with oF3 and oR3 oligonucleotides to detect only tiTERRA (graph on the left) or with oF1 and oR1 oligonucleotides to detect simultaneously tiTERRA and natural TERRA (on the right). Values are normalized to ACT1 mRNA and expressed as fold increase over CAF545 in uninduced conditions (THI+). Bars and error bars are averages and SD from 3 independent experiments. * P < 0.05, ** P < 0.01 (relative to CAF545 THI+; two-tailed Student's t test).",
    "ncbi_link": "ACT1: 
TERRA: "
  },
  {
    "caption": "E Northern blot analysis of total RNA from wt cells and cells carrying two tiTELs (CAF110) treated with combinations of THI and Trichostatin A (TSA) for 24 h. Two identical membranes were hybridized in parallel with oligonucleotides corresponding to C-rich (oC) or G-rich (oG) telomeric repeats. To confirm similar hybridization efficiencies of the two oligonucleotides, northern blot membranes were simultaneously hybridized and exposed along with blots of digested genomic DNA (upper right insets). After signal detection, RNAmembranes were stripped and re-hybridized with U6 probes to assure equal loading. Marker molecular weights are on the left in kilobases.",
    "ncbi_link": "U6: "
  },
  {
    "caption": "A Telomere restriction fragment analysis of genomic DNA from wt cells and cells carrying two tiTELs (CAF110) grown for 24 h in EMM medium containing THI and TSA as indicated. DNA was digested with HindIII and hybridized first with a nmt1 probe and successively with a telomeric probe. Marker molecular weights are on the left in kilobases. Numbers at the bottom indicate gel lanes.",
    "ncbi_link": "nmt1: 2539108"
  },
  {
    "caption": "B Genomic DNA from cells carrying two tiTELs and deleted for trt1+ (CAF113) was analyzed as in (A). Marker molecular weights are on the left in kilobases. Numbers at the bottom indicate gel lanes.",
    "ncbi_link": "trt1: 2540601"
  },
  {
    "caption": "C ter1+ cells carrying two tiTELs (CAF110, left panel) or trt1Δ cells carrying one tiTEL (MKSP2104, central panel) were cultured in EMM medium in presence of THI for 24 h (THI+) or in absence of THI for 24, 48 or 72 h. In the right panel, cells carrying two tiTELs (CAF110) were treated with TSA for 24 h in the presence or absence of THI. TiTEL telomeric sequences were amplified from genomic DNA and sequenced using a PacBio platform. The statistical analysis for each set of conditions is displayed above each panel. P values for each comparison were derived from the Student's t test between each condition and the THI+ sample using Welch's correction when appropriate. The new population of longer tiTELs appearing in trt1Δ cells upon prolonged transcription induction is indicated in red (center panel).",
    "ncbi_link": "ter1: 9407016
trt1: 2540601"
  },
  {
    "caption": "A qRT-PCR analysis of G-rich and polyA+ tiTERRA in cells carrying one tiTEL and expressing Trt1-myc (CAF610) cultured in EMM medium with the indicated combinations of THI and TSA for 24 h. Values are normalized to ACT1 mRNA and expressed as fold increase over THI+ TSA- samples. Bars and error bars are averages and SD from 4 independent experiments. * P < 0.05, ** P < 0.01, *** P < 0.001, (relative to THI+ TSA-; two-tailed Student's t test).",
    "ncbi_link": "ACT1: 
TERRA: 
Trt1: 2540601"
  },
  {
    "caption": "C RIP experiments performed using anti-myc antibodies and extracts from cells as in (A) followed by qRT-PCR analysis of G-rich and polyA+ tiTERRA. Values correspond to fraction of input RNA expressed as fold increase over an untagged (unt) control tiTEL strain (CAF545). Bars and error bars are averages and SD from three independent experiments. * P < 0.05, ** P < 0.01 (relative to unt; two-tailed Student's t test).",
    "ncbi_link": "TERRA: "
  },
  {
    "caption": "using HeLa cells transfected with non-targeting control (CTRL) or SPRTN siRNAs.",
    "ncbi_link": "SPRTN: 83932"
  },
  {
    "caption": "Mass spectrometry-based analysis of formaldehyde-induced SUMOylation changes. His10-SUMO2 conjugates from HeLa/His10-SUMO2 cells subjected or not to formaldehyde were purified on Ni-NTA under stringent conditions and analyzed by mass spectrometry. All proteins displaying significant upregulation of SUMOylation in response to formaldehyde treatment were subjected to network analysis using the STRING database, at the default interaction confidence setting of 0.4. Proteins not connected to the network were omitted.",
    "ncbi_link": "His10: 
SUMO2: 6613"
  },
  {
    "caption": "SUMO2 conjugates from HeLa/His10-SUMO2 cells subjected or not to formaldehyde or heat stress for 1 h were purified and immunoblotted with indicated antibodies.",
    "ncbi_link": "His10: 
SUMO2: "
  },
  {
    "caption": "HeLa cells were transfected with non-targeting control (CTRL) or DNMT1 siRNAs, exposed or not to 5-azadC and collected 2 h later. Chromatin-enriched fractions were immunoblotted with antibodies to SUMO2/3, DNMT1 and MCM6 (loading control).",
    "ncbi_link": "DNMT1: 1786"
  },
  {
    "caption": "Proliferative capacity of HeLa/GFP-DNMT1 cells transfected with indicated siRNAs and exposed to the indicated 5-azadC doses for 2 h was assayed by measuring cell proliferation with the SRB assay (mean±SEM; n=3 independent experiments; ***p<0.001, Student's t-test).",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": "Extracts of HeLa/GFP-DNMT1 cells treated with 5-azadC for the indicated times were subjected to GFP immunoprecipitation (IP) under denaturing conditions followed by immunoblotting with SUMO2/3 and GFP antibodies.",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": "HeLa cells were subjected to consecutive rounds of transfection with DNMT1 siRNA targeting the UTR and expression plasmid encoding WT or catalytically inactive (CI) GFP-DNMT1. Cells were then left untreated or incubated with 5-azadC for 2 h, and SUMOylation of GFP-DNMT1 was analyzed Asterisk denotes unmodified GFP-DNMT1 recognized by the SUMO2/3 antibody due to weak cross-reactivity.",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": "Mass spectrometry analysis of 5-azadC-induced SUMOylation changes. His10-SUMO2 conjugates from HeLa/His10-SUMO2 cells subjected or not to 5-azadC were purified on Ni-NTA under stringent conditions and analyzed by mass spectrometry. Proteins displaying significantly altered SUMOylation in response to 5-azadC treatment relative to the control condition were visualized through two-sample t-testing using permutation-based FDR to achieve q-values of <0.05",
    "ncbi_link": "His10: 
SUMO2: "
  },
  {
    "caption": "SUMO target proteins displaying altered SUMOylation upon DNMT1 knockdown are shown. Both control (CTRL) and DNMT1 siRNA-transfected cells were treated with 5-azadC.",
    "ncbi_link": "DNMT1: 1786"
  },
  {
    "caption": "HeLa cells stably expressing GFP-DNMT1 and transfected with indicated siRNAs were left untreated or exposed to 5-azadC for 2 h. Cells were then preextracted in stringent preextraction buffer and fixed at the indicated time points after 5-azadC removal. Mean detergent-resistant GFP signal was determined by quantitative image analysis (>6000 cells analyzed per condition). Data from a representative experiment are shown.",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": "Proliferative capacity of HeLa/GFP-DNMT1 cells transfected with control or UBC9 siRNAs and exposed to the indicated 5-azadC doses for 2 h was assayed by measuring cell proliferation with the SRB assay (mean±SEM; n=3 independent experiments; ***p<0.001, Student's t-test).",
    "ncbi_link": "GFP: 
DNMT1: 1786
UBC9: 7329"
  },
  {
    "caption": "Proliferative capacity of HeLa cells transfected with SPRTN or ZNF451 siRNAs and exposed to indicated 5-azadC doses for 2 h was assayed",
    "ncbi_link": "SPRTN: 83932
ZNF451: 26036"
  },
  {
    "caption": "HeLa cells stably expressing GFP-DNMT1 were pre-incubated or not with SUMO-E1i for 30 min, and where indicated 5-azadC was added to the medium for an additional 60 min. Cells were then processed for GFP immunoprecipitation (IP) followed by immunoblotting for the indicated proteins.",
    "ncbi_link": "GFP: 
DNMT1: 1786"
  },
  {
    "caption": "Representative images of U2OS cells stably expressing GFP-SPRTN or GFP-ACRC that were transfected with control (CTRL) or UBC9 siRNAs, exposed to formaldehyde in the presence or absence of ubiquitin E1 enzyme (UBA1) inhibitor TAK-243 (Ub-E1i) as indicated and fixed one h later. Scale bar, 10 μm.",
    "ncbi_link": "UBC9: 7329"
  },
  {
    "caption": "Quantification of data showing proportion of U2OS/GFP-SPRTN cells displaying nuclear GFP-SPRTN foci (mean±SEM; at least 100 cells quantified per condition per experiment; n=3 independent experiments). As in (C), but showing proportion of U2OS/GFP-ACRC cells displaying nuclear GFP-ACRC foci (mean±SEM; at least 100 cells quantified per condition per experiment; n=3 independent experiments).",
    "ncbi_link": "GFP: 
ACRC: 93953
SPRTN: 83932"
  },
  {
    "caption": "U2OS cells expressing GFP-ACRC were exposed to the indicated genotoxic agents (formaldehyde: 600 μM, 1 h; UV: 20 J/m2, 6 h recovery; hydroxyurea (HU): 2mM, 24 h; mitomycin C (MMC): 40 ng/mL, 24 h), preextracted and fixed, and analyzed by microscopy. Representative images are shown. Scale bar, 10 μm.",
    "ncbi_link": "GFP: 
ACRC: 93953"
  },
  {
    "caption": "HeLa cells transfected with plasmids encoding GFP alone or indicated GFP-ACRC alleles were subjected to GFP IP under denaturing conditions. Beads were incubated with recombinant polySUMO22-8 chains, washed extensively and processed for immunoblotting with SUMO2/3 and GFP antibodies.",
    "ncbi_link": "GFP: 
ACRC: 93953"
  },
  {
    "caption": "Representative images of U2OS cells expressing indicated GFP-ACRC alleles that were treated with 5-azadC in the presence or absence of SUMO inhibitor (SUMO-E1i), fixed 2 h later and immunostained with DNMT1 antibody. Scale bar, 10 μm.   Quantification of data in (G), showing proportion of cells displaying GFP-ACRC co-localization with DNMT1 foci (mean±SEM; at least 100 cells quantified per condition per experiment; n=3 independent experiments).   ",
    "ncbi_link": "GFP: 
ACRC: 93953"
  },
  {
    "caption": "HeLa cells transfected with plasmids encoding GFP alone, GFP-ACRC or GFP-tagged C. elegans GCNA-1 were subjected to GFP IP under denaturing conditions. Beads were incubated with recombinant polySUMO23-8 chains, washed extensively and processed for immunoblotting with SUMO2/3 and GFP antibodies.",
    "ncbi_link": "GFP: 
ACRC: 93953
GCNA-1: 175850"
  },
  {
    "caption": "GFP expression driven by the gcna-1 promoter was observed in germ cells, proliferating embryos and young larvae but not in post-mitotic tissues in the head Scale bars, 50 µm.",
    "ncbi_link": "gcna-1: 175850"
  },
  {
    "caption": "Formaldehyde survival of wild type (wt), dvc-1, gcna-1 loss-of-function (lof) and gcna-1; dvc-1 double mutant C. elegans (mean±SEM; n=4 independent experiments).",
    "ncbi_link": "dvc-1: 179554
gcna-1: 175850"
  },
  {
    "caption": "Cisplatin survival of wild type, dvc-1, gcna-1 and gcna-1; dvc-1 double mutant C. elegans (mean±SEM; n=3 independent experiments).",
    "ncbi_link": "dvc-1: 179554
gcna-1: 175850"
  },
  {
    "caption": "Formaldehyde survival of gcna-1 deletion (del) and E364Q mutant C. elegans (mean±SEM; n=2 independent experiments).",
    "ncbi_link": "gcna-1: 175850"
  },
  {
    "caption": "Formaldehyde survival of C. elegans grown on L4440 control (CTRL) or smo-1 RNAi bacteria (mean±SEM; n=2 independent experiments).",
    "ncbi_link": "smo-1: 266820"
  },
  {
    "caption": "Formaldehyde survival of C. elegans grown on L4440 control (CTRL) or gei-17 RNAi bacteria (mean±SEM; n=2 independent experiments).",
    "ncbi_link": "gei-17: 172733"
  },
  {
    "caption": "Formaldehyde survival of wild type and gcna-1 deletion (del) mutant C. elegans grown on L4440 control (CTRL) or smo-1 RNAi bacteria (mean±SEM; n=2 independent experiments).",
    "ncbi_link": "gcna-1: 175850
smo-1: 266820"
  },
  {
    "caption": "LC-MS/MS measurements of m6A levels in total RNA (B) or in poly(A)+ RNA (C) upon KD of predicted methyltransferases in Drosophila S2R+ cells. m6A abundance in total RNA is significantly reduced when Mettl5 is depleted, while its depletion has no effect on m6A level in mRNA. As expected, the KD of Mettl3 and Mettl14 reduce m6A levels in mRNA. Bar chart represents the mean ± standard deviation of three technical measurements from three biological replicates. *P < 0.05, **P < 0.01, ***P < 0.001 (two-tailed t-test).",
    "ncbi_link": "Mettl5: 40096
Mettl14: 34138
Mettl3: 42844"
  },
  {
    "caption": "Developmental expression of Mettl5 transcript assayed by RT-qPCR analysis. The figure shows mean ± standard deviation of three technical measurements from three biological replicates.",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "In situ hybridization of Mettl5 transcript at different embryonic stages. The central nervous system (CNS) is highlighted in the schematics. Data retrieved from FlyExpress 7. (http://www.flyexpress.net/search.php?type=image&search=FBgn0036856).",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "LC-MS/MS measurements of m6A levels in total RNA of WT and Mettl5 mutant flies. Bars represent mean ± standard deviation of measurements of three biological replicates. ***P<0.001 (two-tailed t-test).",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "Mature rRNA analysis on ethidium-stained denaturing agarose gels. The same amounts of total RNA extracted from the indicated flies, and from S2R+ cells depleted or not of Mettl5, were loaded. The 28S/18S ratio was established by densitometry.",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "Analysis of 18S rRNA maturation in WT and mutant flies (Mettl5fs). Total RNA extracted from the indicated animals was resolved on denaturing agarose gels and processed for northern blotting with specific probes (complementary to ITS1 or ITS2 sequences). The pre-rRNAs detected accumulate to normal levels indicating that processing is unaffected.",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "Trmt112 depletion reduces m6A levels in total RNA from Drosophila S2R+ cells. Mean ± standard deviation of three technical measurements from three biological replicates. *P < 0.05 (two-tailed t-test).",
    "ncbi_link": "Trmt112: 40343"
  },
  {
    "caption": "Representative trajectories of WT and Mettl5 mutant flies analysed by the Buridan's Paradigm. The blue lines indicate when the fly stops and changes direction. Orientation evaluated with the help of the Buridan's paradigm for Mettl5 mutant flies. Orientation was measured as the angular deviation from the straight path needed to move from one landmark to another in the arena. Number of flies tested per genotype: 30. Mean ± standard deviation. Shapiro-Wilk test was used to test for normal distribution in each group. Normally distributed groups were tested by t-test. Due to multiple comparison Bonferroni correction was applied. (p<0.05 = *; p<0.0001=****).",
    "ncbi_link": "Mettl5: 40096"
  },
  {
    "caption": "A, B Data were normalised using the control group and are represented as fold-change (FC) of the mean fluorescence intensity (MFI). Macrophage  cells were obtained from human  donors (n = 4 biological replicas) and incubated with medium (CON) or recombinant human IL-10 (hIL-10r), MPN    wild-type (WT) or MPN    expressing IL-10  ORF (WT_IL10). Data are represented as mean ± Standard Error of the Mean (SEM). Statistical analysis was performed using one-way ANOVA + post-hoc Tukey multiple comparison test (*P < 0.05; **P < 0.001, ***P < 0.0001).",
    "ncbi_link": "IL-10: 3586
IL10: 3586"
  },
  {
    "caption": "(A) EC-50 (molar, M) for human IL-10 recombinant protein (hIL-10r) and  IL-10 WT (IL-10 ORF) and different variants (MutM, hIL-10r, Mut1, Mut2, Mut3, MutSC1, and MutSC2) expressed by M. pneumoniae. Data are represented as mean ± SD. Statistical comparison was done by One-way ANOVA + post-hoc Bonferroni multiple comparison test, using the IL-10 ORF condition as a reference (*P < 0.05).",
    "ncbi_link": "IL-10: 3586"
  },
  {
    "caption": "(B) Fold-change (FC) in expression  levels (fg/CFU) of IL-10 variants Mut3 and MutSC1 secreted to the medium normalised by expression  level of  IL-10 ORF (ORF). Statistical comparison of mean ± SD was performed by One-way ANOVA + Tukey post-hoc test (*P < 0.05).",
    "ncbi_link": "IL-10: 3586"
  },
  {
    "caption": "(C, D) Average and SD values for the FC in the relative  EC-50 values determined by  flow cytometry analysis of phosphorylated STAT3  after a 20-min exposure of the BlaER1 (C) or HAFTL (D) cell lines to  IL-10 ORF (reference) or the mutant MutSC1 or MutSC2 Numbers indicate the average FC ± SD.",
    "ncbi_link": "IL-10: 3586"
  },
  {
    "caption": "C57Bl/6 were infected with 107 CFUs of WT or CV8  strains and (B) Inflammatory profile of mouse lungs  inoculated with WT (dark blue), CV8  (light blue), or PBS  (grey). Gene expression  was analysed by RT-qPCR  using gapdh  as an endogenous control (see Materials and Methods). Data are shown as average ± SD of fold-change (FC) in mRNA expression (One-way ANOVA + Tukey post-hoc test; *P < 0.05).",
    "ncbi_link": "gapdh: 14433"
  },
  {
    "caption": "C57Bl/6 were infected with 107 CFUs of WT or CV8  strains and (D) IL-10  secretion by the MPN  WT or CV8  strain coding for hIL-10 WT (ORF), MutSC1, or MutSC2. Data are expressed as the mean ± SD of  IL-10 supernatant concentration (μg/mL) by biomass (protein content in μg/mL) (n=3 biological replicas).",
    "ncbi_link": "IL-10: 3586"
  },
  {
    "caption": "(C) Fold-change (FC) of mRNA  gene expression  of inflammatory markers determined by qPCR. The 2-ΔΔCt method was used to normalise the values, using gapdh  as endogenous control Data are shown as average ± SD of FC. Statistical analyses were performed using unpaired t-test (* P < 0.05; ** P <0.01***; P <0.001, **** P <0.0001). Two replicates were performed and individual symbols are shown (Experiment 1, circle; Experiment 2, square).",
    "ncbi_link": "gapdh: 14433"
  },
  {
    "caption": "HEK293T-ACE2-GFP stable cells were transiently transfected with human IFITM plasmids or vector control for 24 h. D) Graph depicts normalized infection percentage measurements from 2-3 independent experiments, each performed in triplicate, from cells infected Bars represent averages with individual data points shown as circles. Error bars represent SD. #p<0.05 compared to vector control by ANOVA followed by Tukey's multiple comparisons test.",
    "ncbi_link": "GFP: 
ACE2: 59272"
  },
  {
    "caption": "HEK293T-ACE2-GFP stable cells were transiently transfected with mouse (m) IFITM plasmids or vector control for 24 h. C) Graph depicts normalized infection percentage measurements from 2-3 independent experiments, each performed in triplicate, from cells infected Bars represent averages with individual data points shown as circles. Error bars represent SD. #p<0.05 compared to vector control by ANOVA followed by Tukey's multiple comparisons test.",
    "ncbi_link": "GFP: 
ACE2: 59272"
  },
  {
    "caption": "U2OS cells transfected with EGFP and the indicated IFITM3 constructs or vector control were mixed Calu-3 cells transfected with mCherry and SARS-CoV-2 Spike (S) or vector control. Cells were co-cultured for 24 h and imaged by fluorescent microscopy to visualize EGFP and mCherry as well as nuclei via Hoechst dye. A) Representative example fluorescent imaging of the indicated co-cultures showing the presence of EGFP/mCherry double positive cell syncytia dependent upon S expression as well as varying effects of the IFITM3 constructs. Scale bar indicates 50 μm. B) Quantification of nuclei per EGFP/mCherry double positive cell syncytia in co-cultures involving the indicated IFITM3 constructs as compared to vector control. Bars depict averages of three independent experiments with circles representing the individual data points. For each condition, nuclei within 50-75 individual syncytia were counted. Error bars represent SD. #p<0.05 compared to vector control by ANOVA followed by Tukey's multiple comparisons test. ",
    "ncbi_link": "EGFP: 
mCherry: 
IFITM3: 10410"
  },
  {
    "caption": "HEK293T-ACE2-GFP stable cells were transiently transfected with human IFITM plasmids or vector control plus TMPRSS2 or vector control for 24 h. B) Graph depicts normalized infection percentage measurements from 3 independent experiments, each performed in triplicate, from cells infected as in (B). Bars represent averages with individual data points shown as circles. Error bars represent SD. The blue dotted line is added to the graph to assist with comparisons to vector control levels of infection. #p<0.05 by ANOVA followed by Tukey's multiple comparisons test. NS, not significant. Not indicated, additional comparisons of interest with p<0.05 include IFITM3 (-) vs. IFITM3-Y20 (-), IFITM3∆59-68 (-), and IFITM3-S61A,N64A,T65A (-).",
    "ncbi_link": "GFP: 
ACE2: 59272
IFITM3: 10410
TMPRSS2: 7113"
  },
  {
    "caption": " (C) qRT-PCR of Reno1, Cox10as1, and lnc-Nr2f1 in ES cells (top) and following eight days of neuronal differentiation (bottom), following knockdown using two different shRNAs, normalized to sh-NT. Mean ± SEM is shown for 3-6 independent experiments, * P<0.05, ** P<0.01 (unpaired two sample t-test). ",
    "ncbi_link": "Cox10as1: 66456
Reno1: 100042332
lnc-Nr2f1: 13865"
  },
  {
    "caption": " (A) Immunostaining using anti-TUJ1 antibody of ES-cell-derived neurons following infection with either non-targeting shRNA (sh-NT), or two different shRNAs targeting Reno1. Scale bar: 200µm. (B) Quantification of cell numbers and neurite lengths of ten images of non-overlapping fields for each shRNA. Mean ± SEM is shown, ** P<0.01 (unpaired two sample t-test). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (C) Mean expression levels of genes which were down- or upregulated following knockdown (KD) of Reno1 or lnc-Nr2f1 during an eight time point neuronal differentiation and maturation of mouse ES cells: Neurons1 corresponds to day in vitro (DIV)1; Neurons2 - DIV7; Neurons3 - DIV16; Neurons4 - DIV21; and Neurons5 - DIV28 (Hubbard et al., 2013). ",
    "ncbi_link": "Reno1: 100042332
lnc-Nr2f1: 13865"
  },
  {
    "caption": "(D) Transcriptional response of cell cycle and neuron-related genes. Heatmaps show log2FC of cells infected with shRNAs targeting Reno1 or lnc-Nr2f1 compared to cells infected with sh-NT, following eight days of neuronal differentiation, and of day eight of differentiation compared to ES cells during differentiation of WT cells.",
    "ncbi_link": "Reno1: 100042332
lnc-Nr2f1: 13865"
  },
  {
    "caption": " (A) Reno1 locus in six vertebrate species. Shaded region indicates the Reno1 locus. Blue gene models are from RefSeq or Ensembl, red gene models are based on PLAR transcript reconstructions (Hezroni et al., 2015). RNA-seq datasets from indicated tissues were taken from publicly-available datasets: BodyMap (Li et al, 2017a) (mouse), Reference Epigenome (human), FAANG (sheep), SRP011985 (opossum), SRP016501 (chicken), DRP000627 (coelacanth). RNA-seq data was scaled separately in each species to the highest coverage in the window, except for opossum and chicken, where a custom upper threshold was set as indicated. ",
    "ncbi_link": "Reno1: 100042332
Reno1: 119545628"
  },
  {
    "caption": " (B) The mouse Reno1 locus. Expression levels during neuronal differentiation of ES cells, in different cellular fractions of ES cells (data from (Engreitz et al, 2016)) and motor neurons (GSE90913), and in forebrain during different stages of embryonic development (data from the ENCODE project). Each set of tracks was normalized separately. ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (C) RENO1 locus in human. Expression levels in dorsolateral prefrontal cortex across six age groups, and in different cellular fractions in fetal and adult cells. Each set of tracks was normalized separately. ",
    "ncbi_link": "RENO1: 119545628"
  },
  {
    "caption": " (D) Reno1 smFISH signal (red) and DAPI staining (blue) in WT and Reno1m/m cells at day eight of neuronal differentiation, imaged using 100x objective. ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (E) Expression levels of Reno1 and Bahcc1 in 30 adult and embryonic tissues. Data from the ENCODE project, quantification was done using RSEM (Li & Dewey, 2011). ",
    "ncbi_link": "Reno1: 100042332
Bahcc1: 268515"
  },
  {
    "caption": "(F) Targeted Chromosome Conformation Capture (4C) using the Reno1 promoter as bait. Top, smoothed trend lines and raw counts of the contact profile in ES cells (red) or differentiated neurons (black); bottom, domainogram showing mean contact per fragment end for a series of window sizes.",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": "(B) Expression levels of Reno1 (both the spliced and unspliced isoforms) and Bahcc1 following four days of differentiation of the indicated cells. Mean ± SEM is shown for 3-4 independent experiments, * P<0.05, ** P<0.01 (unpaired two sample t-test).",
    "ncbi_link": "Reno1: 100042332
Bahcc1: 268515"
  },
  {
    "caption": " (A). Heatmap showing log2-transformed fold changes of Reno1 depleted cells compared to their respective controls. All genes which were significantly differentially expressed (P<0.05) in any of the treatments are shown. (B) Boxplots indicating the median, quartiles, and 5th and 95th percentiles of changes in expression levels of Reno1m/m cells compared to WT cells, for genes with significant (P<0.05) change in cells where Reno1 was perturbed with the indicated method. Number of genes in each group is indicated in the x axis. ** P<0.01 (two-sided Wilcoxon rank sum test). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (C) Mean expression levels of genes in genes which were significantly (P<0.05) dysregulated by at least two out of three Reno1 perturbations at day 2 in fig. 5A (n= 168 down-regulated and 94 up-regulated), during an eight time point neuronal differentiation and maturation of mouse ES cells: Neurons1 corresponds to day in vitro (DIV)1; Neurons2 - DIV7; Neurons3 - DIV16; Neurons4 - DIV21; and Neurons5 - DIV28 (Hubbard et al., 2013). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (D) Expression levels of Reno1 following Dox addition in WT and Reno1m/m cells. Mean ± SEM is shown for three independent experiments, * P<0.05 (unpaired two sample t-test). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (E) Cell count of WT and Reno1m/m cells following four days of differentiation, with or without Dox addition. Cells were harvested from one well of a 6-well plate, and counted using Orflo MOXI Z Mini Automated Cell Counter. Mean ± SEM is shown for three independent experiments. * P<0.05 (unpaired two sample t-test). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (F-G) Boxplots indicating the median, quartiles, and 5th and 95th percentiles of changes in expression levels of WT (F) or Reno1m/m (G) cell treated with Dox for the first two days of differentiation compared to untreated cells, in genes which were significantly (P<0.05) downregulated (n=252) or upregulated (n=223) by at least two out of three Reno1 perturbations at day 2 in fig. 5A, compared to all genes (n=16,511). ** P<0.01 (two-sided Wilcoxon rank sum test). ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": " (A) Boxplots indicating the median, quartiles and 1.5 time the interquartile range of ratios of ATAC-seq signal for the indicated group of peaks, comparing the indicated genotypes or treatments. Core promoter peaks are <300 nt from a TSS; Extended promoter are more than 300 nt but <2 Kb for a TSS; Gene body peaks overlap transcription units, and Intergenic do not. Each group of peaks was compared to the intergenic peaks. In addition, for each group of peaks, the peaks within 1 Mb of Reno1 where compared to peaks further away. P-values computed using two-sided Wilcoxon rank sum test, and shown only for cases where P<0.05. Number of data points (from left to right): 39; 10,777; 11; 3,550; 17; 14,380; 18; 20,930. (B) Changes in ATAC-seq signal for peaks assigned as falling within core or extended promoters, of genes in the indicated group (up/down-regulated by at least 30% and with adjusted P<0.05) in cells with Reno1 (left) or Bahcc1 (right) KD. P-values computed using two sided Wilcoxon rank sum test. ",
    "ncbi_link": "Reno1: 100042332
Bahcc1: 268515"
  },
  {
    "caption": " (C) Top: Boxplots indicating the median, quartiles and 1.5 time the interquartile range of changes in ATAC-seq signal on day 2 of neuronal differentiation of peaks from indicated Reno1 perturbation, classified according to the underlying chromatin state in mouse ES cells; Bottom: Boxplots indicating the median, quartiles and 1.5 time the interquartile range of ChIP-seq coverage of the indicated chromatin marks in ENCODE mouse ES data in the peak regions. Number of peaks in each group is indicated at the bottom. ",
    "ncbi_link": "Reno1: 100042332"
  },
  {
    "caption": "(a) [3H]thymidine incorporation at 72 h by wild-type (WT) and Irgm1-/- CD4+ T cells activated with soluble mAb to CD3 and irradiated syngenic wild-type splenocytes.",
    "ncbi_link": "Irgm1: 15944"
  },
  {
    "caption": "(b) [3H]thymidine incorporation at 72 h by OT-II and Irgm1-/- OT-II CD4+ T cells stimulated with OVA protein (OVA) or OVA peptide of amino acids 323-339 (OVA(323-339)) in the presence of syngenic splenic DCs.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(c,d) Kinetic analysis of [3H]thymidine incorporation (c) and cell numbers (d) in cultures of OT-II and Irgm1−/− OT-II spleen cells stimulated with OVA peptide.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(e) Flow cytometric analysis of the activation and proliferation of OVA peptide-stimulated OT-II and Irgm1-/- OT-II CD4+ T cells pulsed with BrdU during the final 4 h of 72 h of culture and then stained with mAb to CD25 and BrdU. Numbers in quadrants indicate percent viable CD4+ cells.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(f) Enzyme-linked immunosorbent assay of IL-2 produced by OT-II and Irgm1-/- OT-II CD4+ T cells stimulated with OVA peptide in the presence of splenic DCs, measured at 72 h. Data are representative of more than five (a,b) or three (c-f) independent experiments with similar results (mean and s.d. of triplicate cultures, a-d,f).",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(b) Enzyme-linked immunosorbent assay of IFN-γ produced by OT-II and Irgm1−/− OT-II CD4+ T cells stimulated with OVA peptide in the presence of splenic DC in polarized conditions (TH1 or TH2) or nonpolarized conditions (N), assessed in 72-hour cultures. ND, not detected.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(c) Accumulation of polarized and nonpolarized OT-II (open symbols) or Irgm1−/− OT-II (filled symbols) CD4+ T cells after peptide stimulation, quantified by counting of viable cells.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(d) Viable OT-II and Irgm1−/− OT-II CD4+ T cells 72 h after restimulation with OVA peptide in the presence of T cell-depleted APC samples.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(e) Flow cytometry of the viability and division of OT-II and Irgm1−/− OT-II CD4+ T cells stimulated with peptide, allowed to 'rest' for 7 d in IL-2, then labeled with CFSE and restimulated with OVA peptide in the presence of T cell-depleted APC samples and assessed 72 h later.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(f) Flow cytometric analysis of the population expansion of CFSE-labeled OT-II and Irgm1−/− OT-II CD4+ T cells activated with OVA peptide in the presence or absence of IFN-γ-neutralizing mAb. Results in e,f obtained after gating on CD4+ T cells; numbers in outlined areas (e) and in top left corners (f) indicate percent CD4+ cells. PI, propidium iodide.",
    "ncbi_link": "OT-II: 
Irgm1: 15944"
  },
  {
    "caption": "(g) [3H]thymidine incorporation by wild-type, Irgm1−/−, Ifng−/− and Irgm1−/−Ifng−/− CD4+ T cells stimulated for 72 h with soluble agonistic mAb to CD3 and irradiated syngenic Ifng−/− splenocytes. Data are representative of two independent experiments with similar results (mean and s.d. of triplicate cultures, b-d,g).",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(a) Flow cytometric analysis of the survival of CD45.2+ Ifng−/− (open symbols) or Irgm1−/−Ifng−/− (filled symbols) CD4+ T lymphocytes preactivated with agonistic mAb to CD3 in vitro, then transferred intraperitoneally into congenic CD45.1+ C57BL/6.SJL recipients left untreated or inoculated intraperitoneally with T. gondii or M. avium 3 d earlier, assessed in peritoneal exudate cell samples collected at day 4 after transfer.",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(b) Survival of M. avium-infected wild-type, Irgm1−/−, Ifng−/− and Irgm1−/−Ifng−/− mice (n = 5 mice per genotype).",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(c) Flow cytometric analysis of the viability and division of CD4+ T cells labeled with CFSE and activated as described in a with T cell-depleted Ifng−/− APC samples in the presence or absence of IFN-γ (5 U/ml). Numbers in plots indicate percent CFSE+CD4+ T cell populations.",
    "ncbi_link": "Ifng: 15978"
  },
  {
    "caption": "(d-f) Death of Ifng−/− and Irgm1−/−Ifng−/− T cell populations activated with mAb to CD3 and expanded in IL-2, then treated with IFN-γ (d), agonistic mAb to CD3 (e) or Fas ligand (FasL; f), assessed by propidium iodide staining at 48 h after treatment. Open bars, Ifng−/−; filled bars, Irgm1−/−Ifng−/− (a,b,d-f). Data are representative of three independent experiments with similar results (mean and s.d. of triplicate cultures a,b,d-f).",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(a-f) Electron microscopy analysis of Ifng−/− CD4+ lymphocytes (a) and Irgm1−/−Ifng−/− CD4+ lymphocytes (b-f) exposed for 30 h to IFN-γ (5 U/ml). (c) Enlargement of the area outlined in b; arrowheads indicate two autophagic vacuoles. (d) Quantification of vacuoles in 50 randomly selected electron microscopy sections of more than 400 cells. Each symbol represents one section. (e) Irgm1−/− CD4+ T cell with many vacuoles containing dense materials. (f) Two Irgm1−/− CD4+ cells with vacuolated cytoplasma. Original magnification (a-c,e,f), × 1,000. Data are representative of two experiments.",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(g,h) Death of Ifng−/− and Irgm1−/−Ifng−/− CD4+ T cells in the presence or absence of wortmannin or Ly294002 (g), assessed by flow cytometry with propidium iodide staining at 48 h after IFN-γ exposure. Data are representative of three independent experiments (mean and s.d. of triplicate cultures).",
    "ncbi_link": "Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(g,h) Death of Ifng−/− and Irgm1−/−Ifng−/− CD4+ T cells transfected with control or beclin1-specific small interfering RNA, assessed by flow cytometry with propidium iodide staining at 48 h after IFN-γ exposure. Right (h), immunoblot analysis of beclin1 expression. C, control small interfering RNA; B, beclin1-specific small interfering RNA. Data are representative of three independent experiments (mean and s.d. of triplicate cultures).",
    "ncbi_link": "beclin1: 56208
Ifng: 15978
Irgm1: 15944"
  },
  {
    "caption": "(I) Kymographs  of the SPB   (Sfi1-mCherry, yellow) and  histone H2B (Htb1-CFP, blue) in dhc1∆ mutant. At 20 min (white solid lines), dimethyl sulfoxide  (DMSO, as a negative control) or MBC  (final concentration of 20 µg/mL) were added. Dashed lines indicate cell shape. Data information: Scale bars, 5 µm.",
    "ncbi_link": "dhc1: 3361400"
  },
  {
    "caption": "(A) Time-lapse observation of microtubules  (GFP-Atb2, green), dynein   (Dli1-3mCherry, red) and the SPB  (Sad1-CFP, blue) in wild-type and  klp6∆ cells. Arrowheads indicate the SPB. The arrow shows an extensively elongated microtubule  along the  cell cortex in a  klp6∆ cell. Data information: Scale bars, 5 µm.",
    "ncbi_link": "klp6: 2539700"
  },
  {
    "caption": "A-D) Confocal image analysis of cryostat sections from adult CX3CR1+/GFP;Sfrp1+/βgal (A,B); Sfrp1+/βgal (C) and CX3CR1+/GFP;Sfrp1-/- (D) and mouse brains three days after intra-cortical infusion of saline or LPS. Sections were immunostained for βgal (magenta, green in C) and Iba1 (green in A; red in C) or Sfrp1 (magenta) and GFP (green, B and D), and GFAP (cyan in A;B, D, red in C). Arrowheads indicate βgal/GFAP (A) and Sfrp1/GFP co-localization (B). No Sfrp1 protein is detected in the null mice independently of the treatment (two bottom lines). Scale bar 25μm. E) ELISA determination of Sfrp1 levels in brain extracts from 3 months-old wt and Sfrp1-/- mice. WT mice were injected either with saline or LPS. Three days after injection the region around the injected side (10 mm3 cortical cube) was isolated and SFRP1 content compared with that present in similar region of non-injected or Sfrp1-/- mice used as negative control (n=5 mice for each group). Error bars represent Standard Error. Statistical significance: ns P>0.5 ****P<0.0001; One-way ANOVA followed by Bonferroni multiple comparisons test. ",
    "ncbi_link": "GFP: 
CX3CR1: 13051
βgal: 12091
Sfrp1: 20377"
  },
  {
    "caption": "A) Coronal cryostat sections of LV-IRES-Gfp or LV-Sfrp1-IRES-Gfp infected brains 1-month post-infusion, immunostained for SFRP1 (magenta) Iba1 (green) GFAP (cyan), or TauP (red). Lv, lateral ventricle. Scale bar 100μm. B) The graph shows the normalised level of GFAP, Iba1 and CD45 immunoreactivity (IR) and the area occupied by TauP signal (n=24 acquisitions, white dots; N=3 mice, black dots, for each group), normalized to LV-IRES-Gfp infected brains. Error bars represent Standard Error. Statistical significance: *P<0.05; **P<0.01; ****P<0.0001 by two-sided Student's t-test. ",
    "ncbi_link": "Gfp: 
Sfrp1: 20377"
  },
  {
    "caption": "C, D) Coronal sections from wt and Sfrp1-/- mouse brains three days after infusion of saline or LPS, immunostained for GFAP (cyan, C) or CD45 (magenta, D). The images are high power views of the somatosensory cortex (lower power view in Fig EV1D). Scale bar 60μm. E, F) The graphs show the normalised levels of immunoreactivity (IR) for GFAP (E) and CD45 (F, P=0,006) present in cortical sections (n=24 acquisitions white dots; from N=3 animals, black dots, per group) from wt and Sfrp1-/- animals infused with saline or LPS. Bars represent Standard Error. Statistical significance calculated per biological replicas is indicated in green and that based on number of acquisitions in black. ** or ## P<0.01; *** or ### P<0.001; **** or #### P<0.0001 by two-way ANOVA followed by Bonferroni's multiple comparisons test. * and # indicate significance between genotypes and treatments, respectively. ",
    "ncbi_link": "Sfrp1: 20377"
  },
  {
    "caption": "C) Wt and Sfrp1-/- mice immunized with MOG and sacrificed 16 days post immunization. Cryostat sections of the thoracic spinal cords were stained with antibodies against CD4, Iba1, GFAP and MBP. Images show the region dorsal fasciculus. White arrowheads point to the disruption of the pia surface in wt. Scale bar 100μm. D) Quantification of CD4+ infiltrated lymphocytes, Iba1 normalised immunoreactivity, MBP normalised immunoreactivity and MBP immune-reactive area in the dorsal fasciculus of spinal cord sections from wt and Sfrp1-/- mice 16 days after immunization (n=16 acquisitions, white dots; from N=4 animals, black dots, per genotype). Error bars represent Standard Error. Statistic refers to number of acquisitions. ",
    "ncbi_link": "Sfrp1: 20377"
  },
  {
    "caption": "D) ELISA determination of SFRP1 levels present in the media of microglia (n=4 cultures per genotype), astrocytes (n=4 cultures per genotype) or mixed astrocytes and microglial (2:1, n=7 cultures per genotype) cultures derived from wt or Sfrp1-/- pups exposed for 24h to saline or LPS (1μg/ml). Error bars represent Standard Error. Statistical significance: *P<0.05; ***P<0.001; ****P<0.0001; One-way ANOVA followed by Bonferroni Test.",
    "ncbi_link": "Sfrp1: 20377"
  },
  {
    "caption": "B, C) Volcano plots of differential gene expression from CX3CR1GFP/+ (B) or CX3CR1GFP/+;Sfrp1-/- (C) microglial cell in response to LPS. Data are represented as Log2 Fold Change vs -Log10 adjusted p-value by the Wald test corrected for multiple comparisons by the Benjamini and Hochberg method. Blue vertical lines represent an increase of 75 and 400% in the expression levels respectively. Green horizontal lines represent a 0.05 or 0.01 adjusted p-value of statistical significance respectively. Genes with an expression change higher than 75% and an adjusted p-value lower than 0.05 are highlighted in dark red (+FC) and dark blue (-FC). Genes with an expression change higher than 400% and an adjusted p-value lower than 0.01 are coloured in light red (+FC) and light blue (-FC).",
    "ncbi_link": "GFP: 
CX3CR1: 13051
Sfrp1: 20377"
  },
  {
    "caption": "B) Integrative Genomics Viewer transcription profile of represented genes in microglial cells isolated for saline and LPS treated CX3CR1GFP/+ and CX3CR1GFP/+;Sfrp1-/- mouse brains. Scale bar: 2 Kbp.",
    "ncbi_link": "GFP: 
CX3CR1: 13051
Sfrp1: 20377"
  },
  {
    "caption": "(A)  Expression of indicated proteins was determined by western blot  in patient-derived and control fibroblasts and B cells  and A549 OTULIN  WT and KO cells. One representative out of three independent experiments is shown.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "(C) Linear  ubiquitin linkages isolated from  A549 OTULIN KO cells by M1 TUBE assay were incubated with increasing concentrations of recombinant OTULINWT, OTULINM86I and OTULINW167S or catalytically inactive OTULINC129A as control for 1 hour. Afterwards, samples were subjected to analysis by western blot  for the indicated proteins. Images are representative of three independent experiments.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "(A - C)  A549 OTULIN  KO cells were transfected with empty vector or different OTULIN  constructs as indicated and analyzed by  western blot. (D) FLAG-tagged tandem ubiquitin binding entity  (TUBE) assay was performed in B cells  from control, patient, mother and father to pull down linear ubiquitin  linkages. One representative (A - D) of three independent experiments is shown.",
    "ncbi_link": "OTULIN: 90268"
  },
  {
    "caption": "A) SH-SY5Y neuroblastoma cells were either cultivated in RPMI+10% FCS or starved in HBSS with or without addition of LY294002 or rapamycin. After 16 h PINK1 mRNA expression was determined by RT-qPCR and the PINK1 mRNA content of cells kept in RPMI+10% FCS was set as 1. Induction of autophagy by starvation or rapamycin resulted in an induction of PINK1 expression, comparable to the positive control LY294002; n = 4; * expression changes compared to the PINK1 expression in RPMI+10% FCS: LY294002: p<0.01; rapamycin: p<1×10−4; HBSS: p<0.005; HBSS+LY294002: p<5×10−6; HBSS+ rapamycin: p<0.0005; # expression changes compared to the PINK1 expression in RPMI+10% FCS+LY294002: p<0.05; + expression changes compared to the PINK1 expression in RPMI+10% FCS+rapamycin: p<0.0005.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "B) SH-SY5Y cells were either stably transduced with a control (nt) shRNA or a shRNA directed against PINK1 and cultivated in RPMI medium containing 5% or 10% FCS. Their PINK1 mRNA content was determined by RT-qPCR and PINK1 mRNA content of nt cells kept in medium with 10% FCS was set as 1. Serum reduction increased PINK1 mRNA in nt cells in accordance with the data shown in Fig. 1A, while stable PINK1 knockdown (kd) reduced PINK1 content under both conditions; n = 3; * expression changes compared to the PINK1 expression in RPMI+10% FCS: PINK1 kd 10% FCS p<0.0005; PINK1 induction by 5% FCS: p<0.05; # expression changes compared to the PINK1 expression in RPMI+5% FCS: PINK1 kd 5% FCS: p<0.005.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "C) SH-SY5Y cells without (nt) or with stable PINK1 knockdown (kd) were kept in medium with 5% FCS and either untreated or treated for 2 h with CCCP to stabilize PINK1. Afterwards the PINK1 63 kDa protein (arrowhead) and actin protein levels were determined by western blotting (see representative gel on the right). The quantification revealed a reduction of PINK1 protein under both conditions in PINK1 kd cells.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "2A) SH-SY5Y cells were starved for 2 h in HBSS with Bafilomycin (+Baf) or left untreated in RPMI+5% FCS (- Baf). The LC3-II and actin content were determined by western blotting. A representative blot is shown on the right, showing only LC3-II bands in the Bafilomycin-treated samples. The LC3-II bands of Bafilomycin treated samples were normalized to actin and the relative LC3-II content of nt cells was set as 1. Cells with stable PINK1 knockdown exhibited a reduced LC3-II/actin ratio compared to the control (nt) cells; n = 4, p<0.005.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "2B) Cortical neurons from 3 different isolations (10-20 DIV) of WT and PINK1 KO mice were either non-starved or starved for 2 h in HBSS and the LC3-II and actin content was determined by western blotting. A representative blot is shown on the right. The relative LC3-II content of WT and PINK1 KO mice, respectively, was set as 1. Primary neurons showed a strong upregulation of autophagy in reaction to starvation but cells derived from PINK1 KO mice exhibited a reduced LC3-II/actin ratio compared to the WT cells; n = 5, p<0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "2C) HeLa cells were transiently transfected with scrambled siRNA or PINK1 siRNA. After 48 h the LC3-II and actin content was determined by western blotting. A representative blot is shown on the right. The relative LC3-II content of cells transfected with scrambled siRNA was set as 1. Transient PINK1 knockdown resulted in a reduced LC3-II/actin ratio compared to the cells transfected with scrambled siRNA; n = 6; p<0.005.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "2D) HeLa cells were transiently transfected with PINK1-GFP, PINK1G309D-GFP or GFP. After 24 h cells were starved for 2 h in HBSS. Afterwards the LC3-II and actin content were determined by western blotting. A representative blot is shown on the right. The relative LC3-II content of cells transfected with GFP was set as 1. Transient PINK1 or PINK1G309D overexpression resulted in an increased LC3-II/actin ratio compared to cells transfected with GFP; n = 3, PINK1: p<0.01; PINK1G309D: p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "3B) Transduced nt and PINK1 knockdown (kd) SH-SY5Y cells were cultivated either in RPMI+5% FCS or starved for 24 h and 40 h in HBSS. The LAMP-2 and actin content were determined by western blotting. A representative blot after 40 h starvation in HBSS is shown on the right. The relative LAMP-2 content of untreated cells was set as 1. Cells with stable PINK1 knockdown exhibited after 40 h a reduced LAMP-2/actin ratio compared to the nt cells; n = 4, p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "3C) nt and PINK1 knockdown (kd) SH-SY5Y cells were starved for the indicated times with HBSS and afterwards stained for Lamp-2. Micrographs were taken with constant microscopical settings. LAMP-2 positive signals in each cell were quantified with ImageJ as described in Material and Methods. Knockdown of PINK1 resulted in a decreased amount of LAMP-2 positive stainings/cell after starvation; n = 2, at least 8 fields of view/condition, 89-124 cells/condition; 24 h: p<0.001; 40 h: p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "3D) nt and PINK1 knockdown (kd) SH-SY5Y cells were stained with the photo-reactive dye MTR and either irradiated for 45 min or left untreated. 24 h and 48 h after irradiation the LAMP-2 and actin content were determined by western blotting. A representative blot 48 h after irradiation is shown on the right. The relative LAMP-2 content of untreated cells was set as 1. Cells with stable PINK1 knockdown exhibited after 48 h a reduced Lamp-2/actin ratio compared to the control (nt) cells; n = 5, p<0.001.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "3E) Acid phosphatase activity as parameter for lysosomal activity was quantified in nt and PINK1 knockdown (kd) SH-SY5Y cells cultivated in RPMI medium with 5% FCS. The phosphatase activity was measured and normalized to the protein content. The phosphatase activity of nt cells was set as 1. PINK1 knockdown mediated a reduction of lysosomal activity; n = 3; p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "4A) Oxygen consumption rate (OCR) was measured in nt and PINK1 knockdown (kd) SH-SY5Y cells without (nt) or with PINK1 knockdown (kd) cultivated in RPMI medium with 5% FCS. Although oxygen consumption appeared to be slightly impaired in cells with PINK1 kd, no significant changes were observed; n = 1 (quadruplicates).",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "4B) Energy charge (EC) of nt and PINK1 knockdown (kd) SH-SY5Y cells grown in RPMI+5% FCS was determined as detailed in Material & Methods. PINK1 knockdown resulted in a lower EC compared to nt cells; n = 5, p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "4C) nt and PINK1 knockdown (kd) SH-SY5Y cells were grown for 2 months in RPMI+5% FCS and their population doublings were determined. Starting from day 12 cells with PINK1 kd exhibited impaired cell population growth; n = 1 (triplicates); * p<0.05 (day 12) - p<1×10−6 (day 61).",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "4D) SH-SY5Y cells were grown in RPMI+5% FCS and the amount of nt and PINK1 knockdown (kd) cells in S-phase was determined by BrdU incorporation. No differences in cell proliferation were visible between cells without (nt) and with PINK1 kd; n = 3.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "5A) nt and PINK1 knockdown (kd) SH-SY5Y cells were either kept in RPMI medium with 5% FCS or starved with HBSS for 12 h. DEVD cleavage as parameter for caspase-3 activity was analyzed and normalized to the protein content. Cells with PINK1 knockdown demonstrated a significantly increased caspase-3 activity under both conditions; n = 4; RPMI+5% FCS: p<0.05; HBSS: p<0.01.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "5B) nt and PINK1 knockdown (kd) SH-SY5Y cells were either kept in RPMI medium with 5% FCS for 48 h or starved with HBSS for the indicated time points. In the representative western blot the appearance of the PARP 89 kDa cleaved product is depicted as well as GAPDH for normalizing.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "5C) nt and PINK1 knockdown (kd) SH-SY5Y cells were either kept in RPMI medium with 5% FCS for 48 h or starved with HBSS for the indicated time points. For quantification the cleaved PARP 89 kDa product was normalized to the full length 113 kDa PARP and the resulting value normalized to GAPDH. Cells with PINK1 knockdown demonstrated increased PARP cleavage that was significant after 24 h starvation; n = 4; 24 h: p<0.005.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "5D) HeLa cells were transfected with scrambled siRNA or PINK1 siRNA and GFP or GFP-Parkin or PINK1-GFP or PINK1G309D-GFP. After transfection cells were starved for additional 24 h with HBSS and afterwards the amount of adherent cells was determined. The number of adherent cells transfected with scrambled siRNA and the indicated plasmid was set as 1. Starvation-mediated increased cell loss after PINK1 knockdown could be rescued by PINK1 or PINK1G309D-GFP but not by GFP or Parkin; GFP: n = 5, p<0.005; Parkin: n = 3, p<0.05; PINK1: n = 5, ns; PINK1G309D-GFP: n = 3, ns.",
    "ncbi_link": "PINK1: 65018
Parkin: 5071"
  },
  {
    "caption": "5E) HeLa cells and HeLa cells stably overexpressing LC3 were transfected with scrambled siRNA or PINK1 siRNA. After 48 h cells were starved in HBSS for additional 24 h and afterwards DEVD cleavage as parameter for caspase-3 activity was analyzed and normalized to 1,000,000 cells. PINK1 knockdown increased caspase-3 activity significantly, which was prevented by LC3 overexpression; n = 3; p<0.05.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "5F) HeLa cells and HeLa cells stably expressing LC3 were transfected with scrambled or PINK1 siRNA. 48 h post transfection cells were either left untreated (+ medium) or starved (+HBSS) for additional 24 h and afterwards the amount of adherent cells was determined. The amount of non-starved cells was set as 1. PINK1 knockdown resulted in elevated cell loss, which was prevented by LC3 overexpression; HeLa: n = 6, p<0.05; HeLa LC3: n = 5.",
    "ncbi_link": "PINK1: 65018"
  },
  {
    "caption": "(C) pS65-Ub immunoblot of mitochondria-enriched fractions following the paraquat pulse-chase assay in wild-type and park-/- flies. UT, untreated; PQ, 1-day paraquat treatment; Recovery, flies removed from paraquat and returned to normal food. Asterisk (*) denotes non-specific band. (D) pS65-Ub lane densitometry analysis of n = 3 independent replicates from (C), expressed relative to the most intense lane signal in each blot.",
    "ncbi_link": "park: 40336"
  },
  {
    "caption": "(A-B) pS65-Ub immunoblot of whole-animal lysates from untreated flies of the indicated genotypes. park RNAi was induced by da-GAL4 (ubiquitous), Mef2-GAL4 (muscle) or nSyb-GAL4 (neurons). (C) pS65-Ub immunoblot of lysates from bodies or heads (without proboscises), as indicated, from park-/- animals.",
    "ncbi_link": "da: 34413
GAL4: 855828
Mef2: 36032
nSyb: 38196
park: 40336"
  },
  {
    "caption": "(A) pS65-Ub immunoblot of whole-animal lysates from wild-type, Atg5- and park-/- animals harvested at the indicated ages.",
    "ncbi_link": "Atg5: 31666
park: 40336"
  },
  {
    "caption": "(B) pS65-Ub immunoblot of whole-animal lysates from young animals of the following genotypes: wild-type, Pink1-, park-/-, park RNAi (daG4>UAS-park RNAi), Atg1 RNAi (daG4>UAS-Atg1 RNAi), Atg8a-.",
    "ncbi_link": "Atg1: 39454
Atg8a: 32001
park: 40336
Pink1: 31607"
  },
  {
    "caption": "(A-G) Representative images of pS65-Ub immunostaining false-coloured for intensity (Fire LUT) in muscle segments 6/7 from wandering L3 larvae of the following genotypes: (A) wild type, (B) Pink1-, (C) park-/-, (D) Atg5-, (E) Atg8a-, (F) Atg5-; park-/-, (G) Atg8a-; park-/-. (H) Quantification of number of pS65-Ub puncta from A-G displaying mean +/- SEM from the indicated number of animals (n = 3-5 as indicated). (I) Puncta volume from C-G expressed as mean +/- SEM (n = 4-5 animals).",
    "ncbi_link": "Atg5: 31666
Atg8a: 32001
park: 40336
Pink1: 31607"
  },
  {
    "caption": "(A) pS65-Ub immunoblot of whole-animal lysates following paraquat pulse-chase assay of Atg5- flies with parkin overexpression (OE) (Atg55cc5 daG4>UAS-park) compared with Atg5- flies overexpressing mitochondrially targeted GFP (Atg55cc5 daG4>UAS-mito-HA-GFP). UT, untreated flies; PQ, 1-day paraquat treatment; Recovery, flies removed from paraquat and returned to normal food.",
    "ncbi_link": "GFP: 
HA: 
Atg5: 31666
da: 34413
G4: 855828
park: 40336
parkin: 40336"
  },
  {
    "caption": "(b, c) 3D reconstruction (b) and confocal Z-slice (c) of E6.25 WT (left) and RhoAVE-deleted (right) embryos stained for an AVE marker (Cerberus 1, yellow), F-actin (Phalloidin, grey) and mitosis (Phh3, magenta). Scale bar: 25 μm. Blue dotted line delimitates the pro-amniotic cavity (apical side of the epiblast). Red arrowheads point to non-apical mitosis. White lines delimitates the boundary between extraembryonic (up) and embryonic (down) regions of the embryo.",
    "ncbi_link": "RhoA: 11848"
  },
  {
    "caption": "(d) Percentage of AVE migration in WT and RhoAVE-deleted mutants. Data information: Values are shown as Mean ± SEM. WT: n=31 embryos; RhoAVE-deleted: n=17 embryos.",
    "ncbi_link": "RhoA: 11848"
  },
  {
    "caption": "(e) Ratio of non-apical mitosis (non-apical Phh3 over total Phh3, normalised by the volume in μm3) in percentage, in AVE-adjacent and AVE-opposed regions from WT and RhoAVE-deleted embryos.",
    "ncbi_link": "RhoA: 11848"
  },
  {
    "caption": "DNA repair genes involved in HR and FA pathways were differentially expressed over time in response to PORCN inhibition in HPAF-II orthotopic xenografts. Comparison of log2 fold change (FDR < 10%) in the expression of Wnt-activated genes over time across multiple DNA repair pathways shows that genes regulating HR and FA pathways have higher fold changes compared to genes regulating BER, NER or other pathways. BER: base excision repair; HR: homologous recombination; FA: Fanconi anemia; MMR: mismatch repair; NER: nucleotide excision repair; NHEJ: non-homologous end joining; TLS: translesion DNA synthesis. The horizontal line represents median of 4-6 replicates with the upper and the lower edges of the box representing the 75th and 25th percentile of the data respectively and the whiskers representing 1.5 x interquartile range.",
    "ncbi_link": "Wnt: 7471"
  },
  {
    "caption": "H, I. Wnt inhibition reduces the expression of HR and FA pathway genes in a RNF43-mutant pancreatic cancer patient-derived xenograft and AsPC-1 cells. (H) Pancreatic canc­er PDX with G371fs RNF43 mutation treated with vehicle or ETC-159 (30 mg/kg) for 21 days were analysed for changes in the expression of the indicated genes measured by qRT-PCR. Each data point represents an individual tumor. The horizontal lines represent mean of 3 tumors/group. (I) AsPC-1 cells were seeded in low adherence plates, treated with DMSO or ETC-159 (100 nM) for 72 hours and the expression of indicated genes was measured by qRT-PCR.",
    "ncbi_link": "RNF43: 54894
Wnt: 7471"
  },
  {
    "caption": " Stabilized β-catenin prevents the downregulation of HR and FA pathway genes upon Wnt inhibition. Mice bearing HPAF-II xenografts without or with stabilized β-catenin were treated with ETC-159 (37.5mg/kg bid) for 56 hours before tumors were harvested and the expression of indicated genes was measured by qRT-PCR. ETC-159 induced reduction in the expression of HR and FA pathway genes was blocked in xenografts with stabilized β-catenin. The horizontal lines represent mean of replicates",
    "ncbi_link": "β-catenin: 1499"
  },
  {
    "caption": " E, F. G007-LK and olaparib synergistically inhibit the growth of COLO320HSR colorectal cancer cells with APC mutation. COLO320HSR cells were plated at a low density and treated with G007-LK, olaparib or the combination of the two inhibitors at an equivalent dose as described in Figure 1A. (E) Representative image from two independent experiments is shown. (F) The Combination Index (CI) values of olaparib and G007-LK calculated from two independent experiments using the Chou-Talalay CompuSyn software ",
    "ncbi_link": "APC: 324"
  },
  {
    "caption": "β-catenin regulates the expression of MYBL2 in HPAF-II cells. HPAF-II cells were either treated with ETC-159 (100 nM) or transfected with siRNA against β-catenin alone or in the presence of ETC-159 for 48 hours. The relative expression of MYBL2 as measured by qRT-PCR is shown. The horizontal lines represent mean of replicates.",
    "ncbi_link": "β-catenin: 1499
MYBL2: 4605"
  },
  {
    "caption": "Expression of DNA repair genes in Wnt-addicted cells is regulated by MYBL2. HPAF-II cells were transfected with two independent siRNAs against MYBL2 or treated with ETC-159 (100 nM) for 48 hours. Total RNA was isolated and expression of MYBL2 and DNA repair genes was measured by qRT-PCR. Data are representative of three independent experiments. The horizontal lines represent mean of replicates.",
    "ncbi_link": "MYBL2: 4605"
  },
  {
    "caption": "H-K. Expression of MYBL2 is downregulated upon ETC-159 or G007-LK treatment in multiple Wnt-high tumors. Expression of MYBL2 in AsPC-1 xenograft tumors and colorectal cancer PDX (as measured by RNA-seq) or in pancreatic cancer PDX with RNF43 mutation (measured by qRT-PCR) is reduced with ETC-159 treatment. G007-LK reduces MYBL2 expression in COL320HSR cells (measured by qRT-PCR). p-values were calculated with Mann-Whitney U test. Each data point represents an individual tumor or replicate. n = 4-6 samples/group. The horizontal lines represent median of 4-6 replicates with the upper and the lower edges of the boxes representing the 75th and the 25th percentile of the data respectively and the whiskers representing 1.5x interquartile range.",
    "ncbi_link": "MYBL2: 4605
RNF43: 54894"
  },
  {
    "caption": "Immunohistochemical staining of sections of small intestine from C57BL/6J mice for DNA repair proteins shows that the expression of BRCA1, FANCD2 and RAD51 was high in the crypts (Wnt high compartment) whereas the villi did not show any staining. Small intestinal adenomas from APCmin/+ mice displayed positive nuclear immunostaining for HR and FA pathway proteins BRCA1, FANCD2 and RAD51. The bottom panels are higher magnification images of the areas marked in the top panels.",
    "ncbi_link": "APC: 324
Wnt: 7471"
  },
  {
    "caption": "A Box and whiskers (from 5th to 95th percentile) plots depicting TINCR RNA levels in the TCGA SKCM RNA-seq dataset of melanoma samples. TINCR expression is higher in Primary A melanomas, and its reduction in Primary-B melanomas and all groups of metastatic samples is statistically significant (Mann-Whitney test, **p< 0.01). Median, minimum, maximum, 25th, 75th whiskers of expression values are shown.",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "B Scatter-plot showing correlation between the expression of TINCR RNA and normalized rank-sums s of the down-regulated (upper panel) and up-regulated (lower panel) genes in the primary melanoma signature. TINCR expression strongly correlates (Spearman's correlation coefficient of 0.79, Spearman rank p-value: **p<0.01) with the expression of the down-regulated genes.",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "C Dot plot showing qRT-PCR analysis of TINCR expression in primary (8) and metastatic (8) melanoma samples from surgical specimens or patient-derived xenografts (4 primary and 8 metastatic PDXs). TINCR RNA levels relative to the L32P housekeeping gene are shown. Paired primary and metastasis PDXs are marked with an asterisk. The difference between primary and metastatic samples is significant (Mann-Whitney test, **p< 0.01). Median, minimum, maximum, 25th, 75th whiskers of expression values are shown.",
    "ncbi_link": "L32P: 
TINCR: 257000"
  },
  {
    "caption": "A qRT-PCR quantification of TINCR RNA expression in MMC70 and WM902B cell lines, independently infected with two shRNA targeting TINCR expression (shTINCR-1 and -2). Cells transduced with shScamble (shSCR) were used as control. TINCR RNA levels relative to L32P housekeeping gene and control (mean±sd) measured in three independent biological experiments are shown. In both cell lines TINCR knockdown efficiency is more than 70% with the two shRNAs. Statistical analyses were performed using Student t -test (**: p<0.01).",
    "ncbi_link": "L32P: 
TINCR: 257000"
  },
  {
    "caption": "B In vitro migration assay of MMC70 and WM902B cells transduced with shTINCR-1, shTINCR-2 or shSCR. Relative migration (mean±sd) from three independent experiments is indicated. Statistical analyses were performed using Student t -test (***: p<0.001).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "C In vitro cell proliferation of shSCR or shTINCR infected MMC70 and WM902B cells assayed 72h after infection at the indicated time points using CellTiter-Glo luminescent kit (Promega). Cell growth from three biological replicates is indicated as proliferation rate relative to control cells (mean±sd). The difference between control and TINCR-silenced samples at all time points is not significant (Student t-test).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "D Upper panel: in vivo growth of tumors derived from intradermal injection of shTINCR-2 or shSCR WM902B cells in NSG mice. 600,000 WM902B cells per mouse were inoculated. Tumor volumes (mean±sd) were measured 8 weeks after transplantation. Results from two independent experiments (four animals per group) are shown. Statistical analysis between control and TINCR-silenced groups was performed using the Student t -test (**=p<0.01). Lower panel: qRT-PCR analysis of TINCR RNA expression in tumors derived from in vivo transplant of shSCR and shTINCR WM902B cells (8 weeks after injection). TINCR RNA levels relative to L32P housekeeping gene and control (mean±sd) from four biological replicates (animals) from both experiments are shown.",
    "ncbi_link": "L32P: 
TINCR: 257000"
  },
  {
    "caption": "E Drug-response curves showing increased resistance of shTINCR-WM902B cells after treatment with BRAF (Vemurafenib; from 10 to 10,000 nM) and MEK (Trametinib; from 4 to 2,000 nM) inhibitors. The shSCR- (control) and shTINCR-WM902B cells were treated with increasing concentrations of drugs and their viability assayed after 72 hours using CellTiter-Glo luminescent kit (Promega). Error bars represent s.e.m. of three biological replicates. The dose response curve was fit with nonlinear regression (GraphPad Prism).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "G Western blot analysis of a panel of proteins that are specifically associated to the proliferative or invasive phenotype. Total protein lysates were extracted from shSCR- and shTINCR-WM902B cells (lane 1 and 2) or shSCR- and shTINCR-MMC70 cells (lane 3 and 4) 10 days after infection and analyzed by immunoblot assay using the indicated antibodies. Vinculin was used as loading control.",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "A qRT-PCR analysis of TINCR expression (left) of MM13 and MM2 PDX cells infected with lentiviral vectors expressing full-length TINCR cDNA. PDX cells infected with empty vector (Empty) were used as control. TINCR RNA levels relative to L32P housekeeping gene and control (mean±sd) from three biological replicates are shown. Statistical analyses were performed using Student t -test (***: p<0.001).",
    "ncbi_link": "L32P: 
TINCR: 257000"
  },
  {
    "caption": "B In vitro relative migration (mean±sd) from three independent experiments (biological replicates) is shown in MM13 and MM2 TINCR overexpressing (TINCR) compared to control (Empty) cells. Statistical analyses were performed using Student t -test (***: p<0.001).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "C In vitro cell proliferation was assayed 72 hours post infection in Empty and TINCR MM13 and MM2 PDX cells at the indicated time points (1-5 days) using CellTiter-Glo viability assay. Relative proliferation rate (mean±sd) of three independent experiments are shown.",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "D Drug-response curves showing sensitization to MEK inhibitor Trametinib of MM13 (NRAS-mutant PDX) and to Trametinib and BRAF inhibitor Vemurafenib of TINCR MM2 cells (BRAF-mutant PDX). The Empty (control) and TINCR expressing MM13 cells were treated with increasing concentrations of drug (ranging from 5 to 5000 nM) and cell viability was assayed after 72 hours by CellTiter-Glo viability assay. Error bars represent s.e.m. of three biological replicates. The dose response curve was fit with nonlinear regression (GraphPad Prism).",
    "ncbi_link": "BRAF: 673
NRAS: 4893
TINCR: 257000"
  },
  {
    "caption": "E Western blot analysis of the expression of the invasive and proliferative phenotype markers EPHA2, EGFR, AXL, PDGFRβ, SOX10, and MITF in TINCR-overexpressing MM13 and MM2 cells. Total protein lysates were extracted from PDX cells 7 days after infection and analyzed by immunoblot assay using the indicated antibodies. Vinculin was used as loading control. This experiment is representative of three independent experiments showing comparable levels of TINCR overexpression (8-10 folds).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "F In vivo growth of Empty vector and TINCR cDNA expressing MM13 cells following intradermal injection into NSG mice. Four animals (200,000 cells/mouse) per group were used in each experiment. Tumor growth (mean±sd) was monitored weekly and tumor volume (mean±sd) measured at 4 weeks for primary tumors (originated in the site of injection, left panel) and at 8 weeks for spontaneous metastases which colonized lymph nodes (right panel). The results of two independent experiments are shown. Statistical analyses of control and TINCR-overexpressing groups from both experiments were performed using Student t -test (**: p<0.01).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "G Representative pictures of lymph node metastases derived from Empty and TINCR expressing MM13 PDX cells are shown. Hematoxylin-eosin staining of sections of liver and lung metastases derived from Empty and TINCR MM13 PDX cells. Metastasis formation was evaluated 8 weeks after transplantation into NSG mice. Pictures of representative lungs and livers infiltrated with metastases are shown in the inset. Scale bars: 200μm.",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "B Representative comparison of translational efficiency (TE) in control (shSCR) and shTINCR WM902B cells 72h post infection. The genes with statistically significant TE up- and downregulation (FDR< 0.1) are highlighted in red and blue respectively. ATF4 is circled among the upregulated genes.",
    "ncbi_link": "ATF4: 468
TINCR: 257000"
  },
  {
    "caption": "C Heatmap representing top translationally upregulated and down regulated genes in TINCR WM902B cells. The plotted values are the log2 fold TE change values in each biological replicate (rep1 and rep2) relative to control (shSCR).",
    "ncbi_link": "TINCR: 257000"
  },
  {
    "caption": "D Bar-graph representing ribosome protected fragments (RPF) normalized coverage (mean±sd) mapping to ATF4 CDS in control (shSCR) and TINCR (shTINCR) depleted WM902B cells from two biological replicates is shown.",
    "ncbi_link": "ATF4: 468
TINCR: 257000"
  },
  {
    "caption": "E UCSC genome browser tracks of ribosome footprint data illustrating RPF density distribution across ATF4 mRNA in shSCR and shTINCR WM902B cells.",
    "ncbi_link": "ATF4: 468
TINCR: 257000"
  },
  {
    "caption": "B Q-PCR validation of TINCR and ATF4 RNA recovery in TINCR antisense pulldown. Enrichment relative to input (mean±sd) from three independent pulldown experiments is shown. Statistical analyses were performed using Student t -test (**: p<0.01, ***: p<0.001).",
    "ncbi_link": "ATF4: 468
TINCR: 257000"
  },
  {
    "caption": "C UCSC genome browser tracks of TINCR-RIA-seq sequencing reads illustrating coverage and enrichment across ATF4 transcript in WM902B and MMC70 cells.",
    "ncbi_link": "ATF4: 468
TINCR: 257000"
  },
  {
    "caption": "(I-M) The core Atg genes are required for starvation-induced autophagy in both wild-type and CQ-treated skeletal muscles. Dmef2-Gal4, UAS-GFP-Atg8/UAS-Atg1 larvae were starved on low-nutrient food for 6 h (I) or starved on low-nutrient food +2.5 mg/ml CQ for 6 h (J). Note that Atg1 knockdown completely abolished the formation of GFP-Atg8-labeled autophagosomes (compare I-J to C-D). (K-L) Dmef2-Gal4, UAS-GFP-Atg8, Atg1Δ3d larvae failed to form GFP-Atg8 vesicles when starved or starved and treated with CQ. (M) Quantification of autophagy changes due to Atg gene knockdown in Dmef2-Gal4, UAS-GFP-Atg8 larvae starved on low-nutrient food +2.5 mg/ml CQ for 6 h. Each of the 10 UAS-Atg RNAi transgenes tested caused a highly significant decrease (p<.01) in the total area of GFP-Atg8vesicles. SEM is indicated, with n = 5 ventral longitudinal muscles from individual animals.",
    "ncbi_link": "Atg1: 39454"
  },
  {
    "caption": "(B) Glycogen was also detected in muscle from Dmef2-Gal4, UAS-GFP-Atg8 larvae, immunostained with an antiglycogen monoclonal antibody.",
    "ncbi_link": "Atg8: 32001"
  },
  {
    "caption": "(F-G) activation of the Tor pathway blocked autophagy in the muscles from larvae starved on low-nutrient food +2.5 mg/ml CQ for 6 h. (F) Autophagy levels were high in control Dmef2-Gal4/UAS-whitei larvae. Muscles from (G) UAS-Rheb/+; Dmef2-Gal4/+, (H) Dmef2-Gal4/UAS-Tsc1i, and (I) Dmef2-Gal4/UAS-gigi all failed to induce autophagy.",
    "ncbi_link": "gigi: 40201
Rheb: 117332
Tsc1i: 42862"
  },
  {
    "caption": "(A-B) Glycogen phosphorylase is not required for glycogen autophagy (antiglycogen, red; GFP, green; DAPI, blue). (A) UAS-GlyPi/+; Dmef2-Gal4, UAS-GFP-Atg8/+ larvae starved on low-nutrient food +2.5 mg/ml CQ for 6 h exhibited high levels of colocalization between GFP-Atg8 and glycogen.(B) Higher magnification of region outlined in (A)",
    "ncbi_link": "GlyPi: 33386"
  },
  {
    "caption": "C-F) Dmef2-Gal4, UAS-GFP-Atg8 larvae with GlyP and/or Atg1 knockdown were fed on high-nutrient food for 18 h before being starved on low-nutrient food (antiglycogen, red; GFP, green; DAPI, blue). (C) UAS-GlyPi/+; Dmef2-Gal4, UAS-GFP-Atg8/+ larval muscle contained high levels of glycogen prior to starvation, indicating no defect in glycogen synthesis. (D) Following 24 h starvation UAS-GlyPi/+; Dmef2-Gal4, UAS-GFP-Atg8/+ muscles contained no glycogen detectable by antibody staining. (E) Following 24 h of starvation Dmef2-Gal4, UAS-GFP-Atg8/UAS-Atg1i muscles contained no glycogen. (F) Double-mutant larvae UAS-GlyPi/+; Dmef2-Gal4, UAS-GFP-Atg8/UAS-Atg1i larval muscles contained high levels of glycogen after 24 h of starvation, indicating an inability to break down glycogen.",
    "ncbi_link": "Atg1: 39454
GlyP: 33386
GlyPi: 33386"
  },
  {
    "caption": "(G) Time course of glycogen levels in Dmef2-Gal4 carcasses (muscle+body wall) with expression of UAS-RNAi transgenes targeting white, GlyP, Atg1, or GlyP+Atg1. Simultaneous knockdown of GlyP and Atg1, but not either gene alone, significantly reduced glycogen degradation compared to the white control after 24 h of starvation, consistent with immunostaining (C-F). Between 6 and 12 h of starvation, individual knockdown of GlyP or Atg1 caused a significant increase in glycogen levels, indicating a reduced rate of glycogen degradation. SEM is indicated for n = 5-8 samples. The p values were calculated relative to white RNAi control at each time point (*p<.05, **p<.01).",
    "ncbi_link": "Atg1: 39454
GlyP: 33386"
  },
  {
    "caption": "(A-D) Glycogen synthase (GlyS) is required for glycogen synthesis in D. melanogaster muscles. PAS staining for glycogen was absent in Dmef2-Gal4/UAS-GlySi muscles (B) compared to control Dmef2-Gal4/UAS-whitei muscles (A). Antiglycogen immunostaining for glycogen was absent in Dmef2-Gal4/UAS-GlySi muscles (D) compared to Dmef2-Gal4/UAS-whitei control muscles (C).",
    "ncbi_link": "Dmef2: 
Glycogen synthase: 
GlyS: 41823
white: 31271"
  },
  {
    "caption": "(C). (E-K) GlyS is required for the formation of large CQ-induced autophagosomes. Vesicles are much smaller in Dmef2-Gal4, UAS-GFP-Atg8/UAS-GlySi larval muscle starved 6 h in low-nutrient food +2.5 mg/ml CQ (G) than in control Dmef2-Gal4, UAS-GFP-Atg8/UAS-whitei larval muscle (E). (F, H) The difference in autophagosome size is clearly evident at high magnification.",
    "ncbi_link": "Atg8: 32001
GlyS: 41823
GlySi: 41823"
  },
  {
    "caption": "(I-K) Quantification of autophagy changes due to GlyS gene knockdown in Dmef2-Gal4, UAS-GFP-Atg8 larvae starved on low-nutrient food +2.5 mg/ml CQ for 6 h. SEM is indicated, with n = 5 (I) or n = 10 (J-K) ventral longitudinal muscles from individual animals (*p<.05, **p<.01). (I) Each of the four UAS-GlyS RNAi transgenes tested caused a significant decrease in the total area of GFP-Atg8vesicles in the muscle compared to the UAS-whitei control. (J) Vesicle number was unchanged by GlyS knockdown. (K) UAS-GlyS RNAi caused a highly significant decrease in the mean vesicle size (area) compared to the control.",
    "ncbi_link": "Atg8: 32001
GlyS: 41823"
  },
  {
    "caption": "(L-M) GlyS gene expression, monitored using a MiMIC transposon insertion (MI01490), showed expression in the larval muscle (L) but not the fat body (M) (green, GFP; blue, DAPI).",
    "ncbi_link": "GlyS: 41823"
  },
  {
    "caption": "N-O) Larvae were starved on low-nutrient food for 6 h prior to dissection of the fat bodies. Autophagy in Cg-Gal4/+; UAS-GFP-Atg8/UAS-GlySi (O) was not substantially different from autophagy in Cg-Gal4/+; UAS-GFP-Atg8/UAS-whitei control fat bodies (GFP, green; DAPI, blue).",
    "ncbi_link": "Atg8: 32001
GlySi: 41823"
  },
  {
    "caption": ". (P) EM of muscle from Dmef2-Gal4/UAS-GlySi animal starved on low-nutrient food +CQ. Note that the intermyofibril spaces (red asterisk) and sarcomere structure are not distorted.",
    "ncbi_link": "GlySi: 41823"
  },
  {
    "caption": "Q) GlyS or Atg1 knockdown significantly improved the crawling time of larvae treated with CQ and starved for 6 h. SEM is indicated for n = 10 larvae. The p values were calculated relative to white RNAi control larvae (*p<.05, **p<.01).",
    "ncbi_link": "Atg1: 39454
GlyS: 41823"
  },
  {
    "caption": "(B) Western blot/Co-immunoprecipitation (co-IP) showing that Flag-Atg8 binds to a Venus-GlyS or Venus-GlyS (S651A) protein complex in response to starvation. Flag-Atg8 is unable to co-IP with either Venus-GlyS (R593A) or Venus-GlyS (W609A). Venus-GlyS and Venus-GlyS mutants were co-IP'd from muscle lysate from Dmef2-Gal4/UAS-Flag-Atg8 or UAS-Venus-GlyS(WT or mutant)/+;Dmef2-Gal4/UAS-Flag-Atg8third instar larvae. These were fed on high-nutrientfood for 18 h, and then transferred to fresh high-nutrientfood or low-nutrientfood for 6 h.",
    "ncbi_link": "GlyS: 41823"
  },
  {
    "caption": "(C) Venus-GlyS was localized predominantly to the Flag-labeled autophagosomes, with weak staining in the rest of the cytoplasm. (D) Venus-GlyS (R593A) was found throughout the cytoplasm and did not colocalize with autophagosomes. (E) Venus-GlyS (S651A) was localized to the autophagosomes. (F) Venus-GlyS (W609A) did not colocalize with the Flag-labeled autophagosomes.",
    "ncbi_link": "GlyS: 41823"
  },
  {
    "caption": "F smFISH of Arglu1 pre-mRNA (magenta) and Arglu1 sisRNA (green). Merged dots (white, arrowheads) represent Arglu1 pre-mRNA transcript. G Quantification of Arglu1 pre-mRNA and Arglu1 sisRNA copy number from (F). (n = 50 cells) Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum.",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "I RT-PCR of Arglu1 sisRNA, spliced mRNA levels and actin as control after AMOs treatment.",
    "ncbi_link": "actin: 60
Arglu1: 55082"
  },
  {
    "caption": "G Left: Western blot analysis of ARGLU1 protein and GAPDH as loading control in control cells and Arglu1 sisRNA KD cells. Right: Quantification of relative ARGLU1 protein levels normalized to GADPH in Arglu1 sisRNA KD cells vs control cells from western blot analysis (left). (n = 3 biological replicates).",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "M Left: RT-PCR of AXIN1a and AXIN1b spliced levels and actin as loading control in 3 days Arglu1 sisRNA KD cells vs control cells under 100 nM estrogen treatment for 2 hrs. Right: Quantification of relative spliced AXIN1a/AXIN1b expression ratio normalized to actin from RT-PCR analysis (left). (n = 3 biological replicates).",
    "ncbi_link": "actin: 60
Arglu1: 55082
AXIN1a: 8312
AXIN1b: 8312"
  },
  {
    "caption": "B Left: Western blot analysis of ARGLU1 protein and GAPDH as loading control in 1 day Arglu1 sisRNA KD cells vs control cells. Right: Quantification of relative ARGLU1 protein expression level normalized to GADPH in 1 day Arglu1 sisRNA KD cells vs control cells from western blot analysis (left). (n = 3 biological replicates).",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "D Left: smFISH of Arglu1 sisRNA (green) coupled with immunostaining of ARGLU1 protein (red) shown in z-stack. Right: Zoom in z-slice on the boxed area showing co-localization (arrowheads) of Arglu1 sisRNA with ARGLU1 protein. The intensity plot shows the signal quantification and co-localization of Arglu1 sisRNA and ARGLU1 protein in the direction of the white arrow. E Left: smFISH of Arglu1 pre-mRNA (green) coupled with ARGLU1 protein (red) immunostaining shown in z-stack. Right: Zoom in z-slice on the boxed area showing co-localization (arrowhead) of Arglu1 pre-mRNA with ARGLU1 protein. The intensity plot shows the signal quantification and co-localization of Arglu1 pre-mRNA and ARGLU1 protein in the direction of the white arrow.",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "F smFISH of Arglu1 sisRNA (green) and Arglu1 pre-mRNA (magenta) in 1 day Arglu1 sisRNA KD cells vs control cells. G, H Quantification of Arglu1 sisRNA and Arglu1 pre-mRNA copy number from (F). (n = 90 cells). Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum.",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "D Immunostaining of ARGLU1 protein (green) and SC35 (red) in 1 day Arglu1 sisRNA KD cells vs control cells. Zoom in of boxed area and the intensity plot shows the co-localization and signal quantification of ARGLU1 protein and SC35 in the direction of the white arrow.",
    "ncbi_link": "Arglu1: 55082"
  },
  {
    "caption": "E Confocal images of 125 nM ARGLU1-GFP protein (green) only and ARGLU1-GFP protein added with 50 nM IVT RNA (magenta), of either Arglu1 intron 2 with UCE (Intron 2 WT) or IVT Arglu1 intron without UCE (Intron 2 ΔUCE). White arrowhead indicates ARGLU1-GFP droplet incorporated with IVT Intron 2 WT and blue arrowhead indicates free ARGLU1-GFP droplet not incorporated with IVT Intron 2 WT. F Quantification of total ARGLU1-GFP droplets from (E). (n = 3 biological replicates). Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum. G Quantification of average ARGLU1-GFP droplets size with/without incorporation of IVT intron 2 WT from (E, ARGLU1-GFP + Intron 2 WT). (n = 3 biological replicates). Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum.",
    "ncbi_link": "GFP: 
Arglu1: 55082
ARGLU1: 55082"
  },
  {
    "caption": "F Left: Western blot analysis of dARGLU1 protein levels and ACTIN5C as loading control in dArglu1 sisRNA KD ovaries vs control (sibling control, MTD-GAL4/CyO) ovaries. Right: Quantification of relative dARGLU1 protein levels in dArglu1 sisRNA KD ovaries vs control ovaries from the western blot analysis. (n = 3 biological replicates)",
    "ncbi_link": "Arglu1: 34320
GAL4: 855828"
  },
  {
    "caption": "G Left: Immunostaining of dARGLU1 protein (green) and VASA (red) in dArglu1 sisRNA KD germaria vs control (sibling control, MTD-GAL4/TM3) germaria. The asterisk (*) marks the anterior of the germarium. Right: Zoom in of the boxed area and the intensity plot shows the signal quantification of dARGLU1 protein and VASA in the direction of the white arrow.",
    "ncbi_link": "Arglu1: 34320
GAL4: 855828"
  },
  {
    "caption": "Confocal images of 125 nM dARGLU1-GFP protein (green) only and dARGLU1-GFP protein added with 50 nM IVT RNA (magenta), of either dArglu1 intron 2 until the 3' end of sisRNA (dArglu1 intron 2) or IVT dArglu1 intron 2 starting after 3' end of sisRNA (dArglu1 pre-mRNA). White arrowheads indicate dARGLU1-GFP droplets incorporated with IVT dArglu1 intron 2 and blue arrowheads indicate free dARGLU1-GFP droplets not incorporated with IVT dArglu1 intron 2. J Quantification of total dARGLU1-GFP droplets from (I). (n = 3 biological replicates). Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum. K Quantification of average dARGLU1-GFP droplets size with/without incorporation of IVT dArglu1 intron 2 from (I, dARGLU1-GFP + dArglu1 intron 2). (n = 3 biological replicates). Cross, mean; Middle line, median; box, 25th to 75th percentiles; whiskers, minimum to maximum. D",
    "ncbi_link": "Arglu1: 34320"
  },
  {
    "caption": "A Confocal images of 125 nM d/hARGLU1-GFP protein added with 50 nM IVT RNA of either hArglu1 intron 2 WT (magenta) or dArglu1 intron 2 (red). White arrowheads indicate free IVT RNA dots that are not co-localized with the d/hARGLU1-GFP droplets. B Quantification of non co-localized RNA dots from (A, white arrowheads). (n = 16 biological replicates). C, D Quantification of total hARGLU1-GFP droplets and the average droplet size with/without incorporation of IVT hArglu1 intron 2 WT or dArglu1 intron 2 from (A). (n = 3 biological replicates). E, F Quantification of total dARGLU1-GFP droplets and the average droplet size with/without incorporation of IVT hArglu1 intron 2 WT or dArglu1 intron 2 from (A). (n = 3 biological replicates).",
    "ncbi_link": "Arglu1: 55082
Arglu1: 34320"
  },
  {
    "caption": "(D). Parasitemia (percentage %) of cultures of RBC infected by different P. falciparum lines (NF54, Dd2, SL, PfEMP1-KO). The parasites were kept in culture for six days in the presence (Neut.) or absence (Cont.) of neutrophils.",
    "ncbi_link": "EMP1: 810183"
  },
  {
    "caption": "(E). Percentage change in parasitemia following neutrophil challenge of RBCs infected by different parasite lines (NF54, Dd2, SL, PfEMP1-KO).",
    "ncbi_link": "EMP1: 810183"
  },
  {
    "caption": "(G). Short term neutrophil killing of late-stage NF54-luciferase positive RBCs in the presence (red) or absence (blue) of catalase.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(I). Short-term luciferase-based killing assay using neutrophils from three different donors in the presence or absence of 5 uM cytochalasin D.",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(A). Representative flow cytometric analysis of human neutrophils cultured alone (Control), incubated with late-stage NF54 parasites (wild type) or PfEMP1 Knock out (PfEMP1 KO) GFP+ iRBC.",
    "ncbi_link": "EMP1: 810183"
  },
  {
    "caption": "(B). Flow cytometric quantification of the effect of trypsin treatment on neutrophil interaction with wild type and PfEMP1 KO GFP+ iRBC.",
    "ncbi_link": "EMP1: 810183"
  },
  {
    "caption": "(C). Luciferase-based killing assay and neutrophil elimination of late-stage wild type (wt) and PfEMP1ko iRBC.",
    "ncbi_link": "Luciferase: 
EMP1: 810183"
  },
  {
    "caption": "(A) EM analysis of KMnO4-fixed pex3 atg1 and WT cells grown for 16 h on MM-M/G. The inset shows a cluster of vesicles (enlarged from the boxed region).",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(B) iEM analysis of pex3 atg1 cells using α-Pex14 antibodies.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(C and D) FM images of pex3 atg1 cells producing Pex14-mCherry and the ER marker BiPN30-eGFP-HDEL (C), or Pex14-mGFP complemented with Mitotracker orange staining (D).",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(E) Electron tomography analysis of a serial-sectioned pex3 atg1 cell (a) containing a perinuclear membrane cluster (b, arrows). (d-f) 10-nm-thin digital slices through the tomogram reconstruction (viewing direction indicated in c) revealed vesicles (black arrows) and reticular structures (red arrows). The surface-rendered reconstruction in g shows the reticulovesicular structures in 3D viewed at right angles from d. CW, cell wall; M, mitochondrion; N, nucleus; P, peroxisome; V, vacuole. Bars: (A) 500 nm; (A, inset; and B) 100 nm; (C and D) 2.5 µm; (E) 250 nm.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(A) iEM analysis of pex3 cells using α-Pex14 antibodies, identifying structures (arrows) in the vicinity of mitochondria. CW, cell wall; M, mitochondrion. (B) Quantification of Pex14-mGFP spots in pex3 and pex3 atg1 cells.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(C) FM images of pex3 atg1 or pex3 cells, producing Pex14-mGFP complemented with FM4-64 vacuolar staining. The inset (enlarged from the boxed region) shows optimized intensities for pex3 cells, highlighting the Pex14-mGFP spot and vacuolar mGFP.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(A) FM images of pex3 atg1 cells grown for 16 h on MM-M/G. Cells produced Pex14-mCherry and C-terminal mGFP fusions of the indicated proteins.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(B) WB analysis of WT (1) and pex3 atg1 cells (2), grown for 6 or 16 h on MM-M/G.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(C) FM images showing mGFP-fluorescence in pex3 atg1 cells producing Pex14-mCherry (control) or Pex14-mCherry together with the indicated mGFP fusion protein. Cells were grown for 6 h on MM-M/G.",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(D and E) iEM of pex3 atg1 cells using α-Pex5 (D) or α-alcohol oxidase antibodies (E).",
    "ncbi_link": "atg1: 
pex3: "
  },
  {
    "caption": "(H) Colocalization of Pex8-GFP and Pex14-mCherry in pex10 cells.",
    "ncbi_link": "pex10: "
  },
  {
    "caption": "(A) FM images of pex3 cells with Pex14-mCherry upon Pex3-eGFP reintroduction after shifting cells from MM-Glu with ammonium sulfate to MM-M/G with methylamine.",
    "ncbi_link": "pex3: "
  },
  {
    "caption": "(B-E) Live cell FM images of pex3 atg1 cells upon Pex3 reintroduction. Shown are pex3 atg1 cells producing Pex14-mCherry and PAMOPEX3-eGFP (B), PAMOPEX3.PEX10-GFP (C), PAMOPEX3.PMP47-GFP (D), or PAMOPEX3.PTEFGFP-SKL (E). Cells were grown similar to the method in A. The arrows in B-D indicate the first detectable GFP signal. Bars, 2.5 µm.",
    "ncbi_link": "AMO: 
atg1: 
pex3: 
TEF: "
  },
  {
    "caption": "(A and B) WB analysis (A) and protein quantification (B) in WT (lane 1; blue), pex3 atg1 (lane 2; red), and pex3 atg1-PAOXPEX19 (lane 3; green) cells grown for 6 h on MM-M/G. The protein levels in WT were set to 100%.",
    "ncbi_link": "AOX: 
atg1: 
PEX19: 
pex3: "
  },
  {
    "caption": "(C and D) FM images (C) and quantification (D) of Pmp47-mGFP and Pex10-mGFP in pex3 atg1 (1; red) and pex3 atg1-PAOXPex19 (2; green) cells grown for 6 h on MM-M/G. Control cells in D did not produce mGFP. Significance indications: n.s., P < 0.10; *, 0.10 > P > 0.05; **, 0.05 > P > 0.01; ***, P < 0.01. Error bars indicate SD.",
    "ncbi_link": "AOX: 
atg1: 
Pex19: 
pex3: "
  },
  {
    "caption": "(E and F) iEM analysis of pex19 (E) and pex19 atg1 (F) cells using α-Pex14 antibodies.",
    "ncbi_link": "atg1: 
pex19: "
  },
  {
    "caption": "(G) EM analysis of KMnO4-fixed pex3 atg1 pex25 cells grown for 16 h on MM-M/G-showing membrane vesicles (arrows).",
    "ncbi_link": "atg1: 
pex25: 
pex3: "
  },
  {
    "caption": "(H) FM image of pex3 atg1 pex25 cells producing Pex14-mGFP. CW, cell wall; M, mitochondrion; N, nucleus; V, vacuole.",
    "ncbi_link": "atg1: 
pex25: 
pex3: "
  },
  {
    "caption": "(d) Neutrophils (4 × 105/mL) from wild type (WT) mice were incubated with SARS-CoV-2 (MOI = 1) in the presence of WT platelets (4 × 106/mL) or clec2-/- platelets (4 × 106/mL) for 5 h at 37 °C.",
    "ncbi_link": "clec2: 56760"
  },
  {
    "caption": "(a) AAV-hACE2 mice were treated with saline and challenged with SARS-CoV-2 (8 × 104 PFU) for 5 days. Lung tissue sections were stained with DAPI (blue), anti-MPO antibody (green), anti-citrullinated histone H3 (Cit-H3) antibody (red), anti-CD42b antibody (yellow) and anti-CD31 antibody (gray). yellow arrow: NETs (DNA+Gr-1+MPO+Cit-H3+); red arrow: immunothrombosis (NETs + thrombus (CD42b+)), Scale bar is 100 μm.",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "a, b) AAV-hACE2 mice were treated with saline and challenged with SARS-CoV-2 (8 × 104 PFU) for 5 days. Samples were collected at day 5 post-infection, and the collagen were stained with Picro Sirius red (a), while collagen deposition was quantified using MetaMorph software and presented as area (μm2) (b). The images were captured by light microscopy (upper panel) and polarized light microscopy (lower panel). Data are mean ± SEM from two independent experiments (saline: n=3 for 3 d.p.i., n=4 for 5 d.p.i.; isotype: n=3 for 3 d.p.i., n=4 for 5 d.p.i.; prophylactic treatment of CLEC2.Fc treatment: n=5 for 3 d.p.i. and 5 d.p.i.; therapeutic treatment of CLEC2.Fc: n=3 for 3 d.p.i. and 5 d.p.i.). ***p < 0.001, ****p < 0.0001 (Two-way ANOVA).",
    "ncbi_link": "ACE2: 59272"
  },
  {
    "caption": "A) Deletion of the CID domain dramatically reduces the interaction of Nrd1 with Sen1. Coimmunoprecipitation (CoIP) experiments using TAP-tagged Nrd1 (either wt or ∆CID) as the bait. Representative gel of one out of two independent experiments.",
    "ncbi_link": "TAP: "
  },
  {
    "caption": "C) Deletion of the NIM decreases substantially the association of Nrd1 with Sen1. CoIP experiments using Nrd1-TAP as the bait in a SEN1 or sen1∆NIM background. Representative gel of one out of two independent experiments.",
    "ncbi_link": "TAP: 
Nrd1: 855470
SEN1: 851150
sen1: 851150"
  },
  {
    "caption": "D) CoIP experiments using HA-tagged Sen1, either wt or ∆NIM, as the bait. Representative gel of one out of two independent experiments. Protein extracts were treated with RNaseA prior to immunoprecipitation. In these experiment, Sen1 could not be detected in the input extracts.",
    "ncbi_link": "HA: 
Sen1: 851150"
  },
  {
    "caption": "A) Deletion of the N-terminal of Sen1 is lethal. A ∆sen1 strain (YDL2767) covered by an URA3-containing plasmid (pFL38) expressing wt Sen1 was transformed with a TRP1-plasmid (pFL39) carrying either the wt or the mutant versions of SEN1 indicated in the scheme on the left. After over-night growth in non-selective medium, cells were plated on minimal medium (CSM) containing 5-fluorootic acid (5-FOA) to select those that have lost the URA3 plasmid. The absence of growth in 5-FOA implies that the SEN1 version expressed in the TRP1-plasmid does not support viability.",
    "ncbi_link": "SEN1: 851150
Sen1: 851150
sen1: 851150
TRP1: 851570
URA3: 856692"
  },
  {
    "caption": "B) Deletion of the N-terminal domain of Sen1 provokes dramatic defects in transcription termination in vivo. Northern blot analyses of three well-characterized NNS-targets, the CUT NEL025c and the snoRNAs SNR13 and SNR33, in a Sen1-AID (auxin-induced degron) strain carrying an empty vector or a plasmid expressing either the wt or the indicated versions of SEN1. Sen1-AID was depleted for 2h by the addition of 500 μM indole-3-acetic acid (IAA) to monitor the capacity of the plasmid-borne versions of SEN1 to induce transcription termination. The expected RNA species resulting from inefficient termination (RT for readthrough species) are indicated. assays were performed in a ∆rrp6 background to detect the primary products of NNS-dependent termination and the U4 RNA is used as a loading control.",
    "ncbi_link": "NEL025c: 
U4: 
rrp6: 854162
SEN1: 851150
Sen1: 851150
SNR13: 9164878
SNR33: 9164874"
  },
  {
    "caption": "C) Overexpression of sen1∆Nter restores viability. Growth test of strains harboring the indicated version of SEN1 at the endogenous locus under the control of the GAL1 promoter (pGAL) in the presence of galactose.",
    "ncbi_link": "GAL: 
GAL1: 852308
SEN1: 851150
sen1: 851150"
  },
  {
    "caption": "D) Overexpression of SEN1 partially suppresses the termination defects associated with deletion of the N-terminal domain. Northern blot analysis of a typical NNS-target in strains expressing the indicated SEN1 versions from pGAL in the presence of galactose. assays were performed in a ∆rrp6 background to detect the primary products of NNS-dependent termination and the U4 RNA is used as a loading control.",
    "ncbi_link": "GAL: 
U4: 
rrp6: 854162
SEN1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. A) Metagene analysis of the RNAPII distribution relative to the annotated polyadenylation site (PAS) of mRNAs. Values on the y axis correspond to the median coverage. B) Box-plot representation of the readthrough (RT) index as a readout of the termination efficiency at each mRNA. The RT index was calculated as the average signal over a window of 200 nt downstream of the PAS, divided by the average signal from the TSS to the PAS of each mRNA. Boxes include all the values between the 25th and the 75th percentiles and the horizontal line indicates the median. The upper error bars indicate the distance between the largest value smaller than or equal to the upper limit of the box + 1.5 *IQR (where IQR is the interquartile distance or distance between the first and the third quartile). The lower error bars indicate the distance between the lowest value greater than or equal to the lower limit of the box - 1.5 *IQR. For each mRNA (n=5752), the values correspond to the average of two independent biological replicates. Data populations were compared using a t-test (bilateral distributions, unpaired data) and p-values≥ 0.05 are indicated as ns (not significant).",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. C-D) IGV screenshots of two well-characterized protein-coding genes displaying substantial defects in premature termination in some mutants. The values correspond to the counts per million of counts (CPM) multiplied by 10.",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. E) Metagene analyses of transcribing RNAPII at CUTs performed as for mRNAs but using the annotated transcription termination site (TTS) as the reference point. F) Analysis of termination defects in the different mutants at CUTs. Box-plots performed as in (B). The RT index is calculated as the average signal over a window of 400 nt downstream of the TTS, divided by the average signal over a window of 100 nt downstream from the TSS (CUT100). For each CUT (n=329), the values correspond to the average of two independent biological replicates. P-values < 0.001 are indicated by three asterisks. ",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. G-H) IGV screenshots of examples of CUTs displaying substantial termination defects in the mutants.",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. Analysis of RNAPII occupancy around snoRNAs performed as for CUTs. Box-plots performed as in (B). The RT index is calculated as the average signal over a window of 300 nt downstream of the TTS, divided by the average signal over the mature snoRNA.",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "RNAPII CRAC were performed in the presence of the indicated versions of SEN1 expressed from its own promoter in a centromeric plasmid, upon depletion of the chromosomally-encoded version of Sen1 in a Sen1-AID strain. Analysis of RNAPII occupancy around snoRNAs performed as for CUTs.",
    "ncbi_link": "SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "A) Deletion of Sen1 N-terminal domain does not prevent the interaction of Sen1 with RNAPII. CoIP experiments using Rbp3-FLAG as the bait. Assays were performed in a Sen1-AID strain harboring a plasmid expressing either SEN1 or sen1∆Nter upon depletion of Sen1-AID in the presence of IAA for 2h. An asterisk denotes a major proteolytic Sen1 fragment detected in the extracts of roughly the size of sen1∆Nter. Nrd1 is detected as a positive control. Representative gel of one out of two independent experiments. Protein extracts were treated with RNaseA before immunoprecipitation.",
    "ncbi_link": "FLAG: 
Rbp3: 854791
SEN1: 851150
Sen1: 851150
sen1: 851150"
  },
  {
    "caption": "B) Deletion of the Sen1 N-terminal domain reduces the interaction of Sen1 with the S5P-CTD. CoIP experiments using TAP-Sen1 as the bait. Sen1 proteins were expressed from pGAL in the presence of galactose. Nab3 is detected as a positive control. Representative gel of one out of three independent experiments. Protein extracts were treated with RNaseA before immunoprecipitation.",
    "ncbi_link": "GAL: 
TAP: 
Sen1: 851150"
  },
  {
    "caption": "C) Replacing the Nter of Sen1 by the CID of Nrd1 restores viability. Growth test performed in the same conditions as in figure 3A but in the presence of a TRP1-plasmid carrying the SEN1 versions indicated in the scheme on the left. The growth of the strain expressing the Nrd1 CID-sen1∆Nter chimera in 5-FOA implies that this gene can support viability.",
    "ncbi_link": "Nrd1: 855470
SEN1: 851150
Sen1: 851150
sen1: 851150
TRP1: 851570"
  },
  {
    "caption": "D) Substituting the Nter of Sen1 by Nrd1 CID but not Pcf11 CID partially suppresses the termination defects detected in the sen1∆Nter mutant. Northern blot assays performed in a Sen1-AID strain carrying an empty vector or a plasmid expressing the indicated versions of SEN1 upon depletion of the endogenous Sen1 protein as in figure 3B. Experiments performed in a ∆rrp6 background. Representative gel of one out of two independent experiments.The U4 RNA is used as a loading control.",
    "ncbi_link": "U4: 
Nrd1: 855470
Pcf11: 851814
rrp6: 854162
SEN1: 851150
Sen1: 851150
sen1: 851150"
  },
  {
    "caption": "E) Sen1 Nter interacts with the C-terminal domain (Cter) of Sen1 both in the presence and in the absence of the NIM in vitro. Pull-down experiments using either a wt or a ∆NIM version of recombinant Sen1 Cter immobilized on glutathione-sepharose beads and a TAP-tagged version of Sen1 Nter expressed in yeast. Representative gel of one out of three independent experiments.",
    "ncbi_link": "TAP: 
Sen1: 851150"
  },
  {
    "caption": "A-C) Comparison of the distribution of Sen1 and RNAPII (Rpb1) at mRNAs and CUTs. Values on the y axis correspond to the median coverage. Note that the scale of Sen1 and Rpb1 datasets have been modified to be able to visualize both in the same plot.",
    "ncbi_link": "Rpb1: 
Sen1: 851150"
  },
  {
    "caption": "G) Metagene analysis of the distribution of the different Sen1 variants at mRNAs using either the TSS or the PAS as reference point. Values correspond to the median of Sen1 data normalized by the RNAPII signal obtained in the corresponding background.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "H-I) Screenshots of two well-characterized protein-coding genes that are regulated by NNS-dependent premature termination. Values correspond to unnormalized Sen1 occupancy.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "J) Profile of Sen1 binding at CUTs calculated as for mRNAs.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "K-L) Examples of CUTs exhibiting differences in Sen1 occupancy upon deletion of the NIM or the Nter. Plots correspond to unnormalized data.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "M-O) Analysis of the distribution of the different Sen1 versions around snoRNAs performed as for CUTs.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "P) Comparison of the total levels of the different Sen1 variants at mRNAs, CUTs and the termination region of snoRNAs (i.e. a window of 200 nt downstream of the 3' end of the mature snoRNA, snoRNA-ter). Boxes in box-plots include all the values between the 25th and the 75th percentiles and the horizontal line indicates the median. The upper error bars indicate the distance between the largest value smaller than or equal to the upper limit of the box + 1.5 *IQR. The lower error bars indicate the distance between the lowest value greater than or equal to the lower limit of the box - 1.5 *IQR. Datasets for the different Sen1 versions were compared using a t-test (bilateral distributions, unpaired data). p-values≥ 0.05 are indicated as ns (not significant), one asterisk is used when 0.05>p-value≥0.01, two asterisks when 0.01>p-value≥0.001 and three asterisks for p-value <0.001.",
    "ncbi_link": "Sen1: 851150"
  },
  {
    "caption": "A) Decreasing the elongation rate alleviates the termination defects associated with deletion of Sen1 Nter. Northern blot assays performed in a Sen1-AID, ∆rrp6 strain carrying a plasmid expressing the indicated versions of SEN1 upon depletion of the endogenous Sen1 protein as in former experiments. Where indicated, cells were treated with 50 mg/L of 6-azauracile (6AU) for 2h. Representative gel of one out of two independent biological replicates.The U4 RNA is used as a loading control.",
    "ncbi_link": "U4: 
rrp6: 854162
SEN1: 851150
Sen1: 851150"
  },
  {
    "caption": "(b-e) Induction of conventional macroautophagy in WT and Ulk1gt/gt, but not in Atg5−/−, embryonic erythroid cells. Ter119+ erythroid cells from WT, Atg5−/−, and Ulk1gt/gt embryonic mice (E18.5) were treated with 1 μM rapamycin (b,c) and 1 μM STS (d,e), and then harvested at the indicated times. (b,d) Representative protein expression of LC3 and p62 measured by western blot. Actin was a loading control. Uncropped images are shown in Supplementary Fig. 10. (c,e) Semi-quantitative analysis of LC3-II/LC3-I and p62 protein expression (n=3, mean±s.d.). Asterisks indicate a significant difference at P0.05 (analysis of variance (ANOVA)). #P0.05 versus value of WT 24 h (ANOVA). 'NS' indicates not significant (ANOVA).",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "(b-e) Induction of conventional macroautophagy in WT and Ulk1gt/gt, but not in Atg5−/−, embryonic erythroid cells. Ter119+ erythroid cells from WT, Atg5−/−, and Ulk1gt/gt embryonic mice (E18.5) were treated with 1 μM rapamycin (b,c) and 1 μM STS (d,e), and then harvested at the indicated times. (b,d) Representative protein expression of LC3 and p62 measured by western blot. Actin was a loading control. Uncropped images are shown in Supplementary Fig. 10. (c,e) Semi-quantitative analysis of LC3-II/LC3-I and p62 protein expression (n=3, mean±s.d.). Asterisks indicate a significant difference at P0.05 (analysis of variance (ANOVA)). #P0.05 versus value of WT 24 h (ANOVA). 'NS' indicates not significant (ANOVA).",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "(a) Induction of alternative macroautophagy in WT and Atg5−/−, but not Ulk1gt/gt and DKO, erythroid cells. Erythroblasts and reticulocytes from the liver of embryonic mice (E18.5) were incubated with or without STS (1 μM) for 24 h, followed by staining with anti-Lamp2 (red), anti-Ter119 (green) and DAPI (blue). DAPI-positive erythroblasts and DAPI-negative reticulocytes are shown. Lamp2 image and merged image (DAPI, Ter119 and Lamp2) are shown. Scale bar, 1 μm. Large dots for Lamp2 are observed in STS-treated WT and Atg5−/− cells, but not STS-treated Ulk1gt/gt or DKO cells.",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "(b) Representative electron micrographs of EC incubated with or without STS. Erythroid cells were harvested from the liver of embryonic mice (E18.5), incubated with or without STS (1 μM) for 24 h, and analysed by electron microscopy (EM). Scale bar, 1 μm. Insets of WT and Atg5−/− cells show mitophagy (Scale bar, 0.5 μm). Inset of a Ulk1gt/gt cell showing mitochondria that have not been engulfed (Scale bar, 0.5 μm). Arrows point to non-engulfed mitochondria and the arrowheads indicate engulfed mitochondria. (c-e) Quantitative analysis of mitophagy after STS treatment, calculated from EM photos. Population of reticulocytes with mitophagy (c), number of mitochondria per reticulocytes (d) and population of reticulocytes showing macroautophagy (e) were calculated (n>35 cells per mouse). The data are shown as mean±s.d. (n=3). *P0.05 versus value of WT (analysis of variance (ANOVA)); #P0.05 versus value of Atg5−/− (ANOVA); 'NS' indicates not significant versus value of WT (ANOVA).",
    "ncbi_link": "Atg5: 11793
Ulk1: 22241"
  },
  {
    "caption": "(c) The percentage of CD71−Ter119+ cells without mitochondria was determined by gating the mitochondrialow fraction, as shown in (b) (mean±s.d., n=6). *P0.05 versus value of WT (analysis of variance (ANOVA)); #P0.05 versus value of Atg5−/− (ANOVA); 'NS' indicates not significant versus value of WT (ANOVA).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(d) Percent mitochondrialow cells in the CD71−Ter119+ EC of Atg7F/FCre embryo. Erythroid cells from the liver and peripheral blood of WT and Atg7F/FCre embryo (E18.5) were stained with anti-Ter119, anti-CD71, and Mitotracker Deep Red (mean±s.d., n=3). *P0.05 versus value of WT (Student's t-test).",
    "ncbi_link": "Cre: 
Atg7: 74244"
  },
  {
    "caption": "(e) Percentage of mitochondrialow cells in Syto16low cells. Liver erythroid cells (E18.5) were stained with Syto16 (DNA) and Mitotracker Deep Red. Representative dot plots of the mitochondrial content of Syto16low cells are demonstrated in Supplementary Fig. 5, the percentage of Syto16low cells without mitochondria was determined by gating the mitochondrialow fraction (mean±s.d., n=6). *P0.05 versus value of WT (ANOVA); #P0.05 versus value of Atg5−/− (ANOVA); 'NS' indicates not significant versus value of WT (ANOVA).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(f) Immunofluorescent analysis of mitochondrial and lysosomal proteins. Liver Ter119+ cells (E18.5) of the indicated mice were stained with anti-Tom20 (mitochondrial marker) and anti-Lamp2 (lysosomal marker) antibodies, and observed by fluorescent microscopy. Scale bar, 2 μm. Green, red, white, and blue indicate Tom20, Lamp2, Ter119 and DAPI (DNA), respectively. Mitochondrial and lysosomal markers have separate distributions in Ulk1gt/gt cells and DKO cells.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(a-f) Representative EM of WT (a), ATG5−/− (b), Ulk1gt/gt (c,d) and DKO (e,f) reticulocytes from embryonic liver (E14.5). (a,b) Mitophagy was detected in WT and ATG5−/− cells (scale bar, 1 μm). Insets indicate mitophagy (scale bar, 0.2 μm). (c,e) In Ulk1gt/gt and DKO cells, numerous mitochondria were in contact with membrane structures (scale bar, 1 μm). Enlarged images are shown on the right side (scale bar, 0.2 μm). (d,f) Some Ulk1gt/gt and DKO cells showed plasma membrane blebs containing mitochondria (scale bar, 1 μm). (g,h) Quantitative analysis of mitophagy calculated from EM photos in the embryonic liver at E18.5. Population of reticulocytes with mitophagy (g), and number of mitochondria per reticulocytes (h) were calculated (n>35 cells per mouse). The data are shown as mean±s.d. (n=3). *P0.05 versus value of WT (analysis of variance (ANOVA)); #P0.05 versus value of Atg5−/− (ANOVA); 'NS' indicates not significant versus value of WT (ANOVA).",
    "ncbi_link": "ATG5: 11793
Ulk1: 22241"
  },
  {
    "caption": "(b) Semi-quantitative analysis of the expression level of each protein and the LC3-II/LC3-I ratio (mean±s.d., n=3). *P0.05 versus value of WT EC (analysis of variance (ANOVA)); #P0.05 versus value of Atg5−/− EC (ANOVA); 'NS' indicates not significant versus value of WT EC (ANOVA).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(c,d) Percentage of Syto16low cells without mitochondria. Differentiated cells were stained with Syto16 and Mitotracker Deep Red. Representative histograms of mitochondrial content in Syto16low cells on day 6 are shown in (c). Numbers indicate the population of mitochondrialow cells. Representative dot plots are also available in Supplementary Fig. 13. (d) Percentage of Syto16low cells lacking mitochondria determined by gating the mitochondrialow fraction as shown in (c) (mean±s.d., n=6). *P0.05 versus value of WT (analysis of variance (ANOVA)); #P0.05 versus value of Atg5−/− (ANOVA); 'NS' indicates not significant versus value of WT (ANOVA).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(i)Impact of various drugs on mitochondrial clearance during in vitro differentiation.with cells from Atg5−/− embryos exposed to wortmannin or 3-MA (mean±s.d., n=3). *P0.05 versus value of no drug (ANOVA).",
    "ncbi_link": "Atg5: 11793"
  },
  {
    "caption": "(e) Representative electron micrographs of bone marrow reticulocytes in 10 week-old WT and Ulk1gt/gt mice (scale bar, 1 μm). Insets indicate mitophagy (scale bar, 0.2 μm).",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(h,i) The impact of Ulk1 on mitochondrial clearance during stress erythropoiesis. (h) Representative images of erythrocyte in PHZ-treated WT and Ulk1gt/gt mice (14 weeks old). Blood cells were stained with anti-Ter119 (erythroid cell marker) and anti-Tom20 (mitochondrial marker) antibodies and observed by fluorescence microscopy. Green and red indicate Ter119 and Tom20, respectively. Scale bar, 10 μm. (i) Percentage of mitochondrialow cells among Syto16low cells. Erythroid cells were stained with Syto16 (DNA) and Mitotracker Deep Red (mean±s.d., n=3). *P0.05 versus value of WT (Student's t-test). Mitochondrial retention was observed in Ulk1gt/gt mice.",
    "ncbi_link": "Ulk1: 22241"
  },
  {
    "caption": "(B) Assessment of exogenous DDX60  expression. HEK293T  cells transfected with DDX60  wild type (wt), or DDX60  mutants and analyzed by  western blot for DDX60, ß-actin and GAPDH (loading controls), and RFP  (reporter). DDX60  and RFP  quantification relative to GAPDH from one representative blot  are shown below.",
    "ncbi_link": "DDX60: 55601"
  },
  {
    "caption": "(C) HCV antiviral assays with DDX60  wt or mutant panel. Huh-7  cells transfected with an RFP  containing plasmid backbone encoding either Firefly luciferase  (Fluc, negative, and transfection control), IRF1  (positive antiviral control), DDX60  wt, or DDX60  mutants and infected with HCV-Ypet, a bicistronic reporter HCV  where Ypet  reporter protein is driven by HCV  IRES  and HCV  polyprotein consisting of C, E1, E2, p7, NS2, NS3, 4A, 4B, NS5A, and NS5B  is driven by EMCV  IRES. Data information: For (C) percent of Ypet+ cells in RFP+ cells is scaled to one replicate of Fluc  control. Data shows mean ± SD for at least n=3 biological replicates; ns = not significant, *p < 0.05, ****p < 0.0001, ns, non-significant using ANOVA and Dunnett's multiple comparison test against Fluc.",
    "ncbi_link": "Fluc: 
luciferase: 
RFP: 
Ypet: 
DDX60: 55601
IRF1: 3659"
  },
  {
    "caption": "(D) Effect of DDX60  on replication of bicistronic or monocistronic infectious reporter HCVs. Huh-7 cells transfected as in (C) and infected with either bicistronic HCV-Ypet   (left) or monocistronic HCV  J6/JFH-5AB-YPet. Ypet  reporter in monocistronic HCV  is placed in between NS5A  and NS5B. Data information: For (D), percent of Ypet+ cells in RFP+ cells is scaled to one replicate of Fluc  control. Data shows mean ± SD for at least n=3 biological replicates; ns = not significant, *p < 0.05, ****p < 0.0001, ns, non-significant using ANOVA and Dunnett's multiple comparison test against Fluc.",
    "ncbi_link": "Fluc: 
YPet: 
Ypet: 
DDX60: 55601"
  },
  {
    "caption": "(A) Plasmid-based dual luciferase bicistronic reporter assays. HEK293T  cells co-transfected with  dual luciferase bicistronic reporter plasmid  (Renilla luciferase  (Rluc) translationally driven by a 5' cap, and Firefly luciferase  (Fluc) translationally driven by different IRESs  as indicated) and GFP  plasmid (negative control) or increasing amounts of IRF1  (positive control), DDX60  wt, or DDX60  E890A mutant. Total amount of DNA transfected was kept constant by supplementing transfection mixes with GFP  plasmid. Luciferase  units after cell lysis is plotted as a percentage of GFP   transfected cells (left) and ratio of IRES Fluc  units over 5' cap Rluc  units (middle). Diagram to the right of ratios plot depicts expected ratios of IRES-driven Fluc  units to 5' cap-driven Rluc  units given either: equal translation of 5' cap-driven Rluc  and IRES-driven Fluc  (top), greater translation of IRES-driven Fluc  (middle), or greater translation of 5' cap-driven Rluc  (bottom). Data information: Data shows mean ± SD for at least n=3 biological replicates; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns, non-significant using ANOVA and Dunnett's multiple comparison test against GFP.",
    "ncbi_link": "DDX60: 55601
IRF1: 3659"
  },
  {
    "caption": "(B) RNA-based monocistronic  luciferase reporter assays. HEK293T  cells transfected with GFP  (negative control), IRF1  (positive control), DDX60  wt, or DDX60  E890A and subsequently transfected with in vitro transcribed 5' cap or different IRES  driven Fluc  mRNA constructs as indicated. Luciferase  units after cell lysis is plotted as a percentage of GFP  transfected cells. Data information: Data shows mean ± SD for at least n=3 biological replicates; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns, non-significant using ANOVA and Dunnett's multiple comparison test against GFP.",
    "ncbi_link": "Fluc: 
GFP: 
DDX60: 55601
IRF1: 3659"
  },
  {
    "caption": "(A-E) (A, B, E) Multi-cycle infection  assays with type I and type II IRES containing viruses. HeLa  cells stably expressing Firefly luciferase  (Fluc) (negative control), IRF1  (positive control), DDX60  wt, or DDX60  E890A and infected with (A) encephalomyocarditis virus, (B) poliovirus, or (E) a chimeric poliovirus  with the poliovirus  IRES replaced with the IRES of EMCV  (EMCV-IRES-PV) at MOI 0.001. Supernatants were collected 24 hours post infection  (hpi) (EMCV) or 48 hpi (poliovirus  and EMCV-IRES-PV) and titers determined via plaque assay on HeLa  cells. (C, D) Single-cycle infection  assays  with type I and type II IRES containing viruses. BHK-J cells stably expressing empty vector (negative control), IRF1  (positive control), DDX60  wt, or DDX60  E890A and infected with (C) foot and mouth disease virus, or (D) bovine enterovirus-1 at MOI 1. Supernatants were collected 5 hours post infection  (hpi) and titers determined via plaque assay on BHK-21  clone 13  cells. Data information: Data shows mean ± SEM percent infectious  titers relative to Fluc  from at least n=3 biological replicates; *p < 0.05, **p < 0.01, ***p <0.001, ****p<0.0001, ns, non-significant using ANOVA and Dunnett's multiple comparison test against DDX60  E890A.",
    "ncbi_link": "Fluc: 
luciferase: 
DDX60: 55601
IRF1: 3659"
  },
  {
    "caption": "B) HEK293T  cells transfected with DDX60  wt or DDX60  E890A (negative control) and transfected with in vitro transcribed 5' cap- or IRES-driven Fluc  mRNA constructs as indicated and lysed 16 hours later. (B) IRES- or cap-driven translation from the same samples assayed in parallel using luciferase assay. Data information: B) Mean ± SD from at least n=3 biological replicates; ****FDR < 0.01% (p<0.0001) using unpaired t-test with Welch correction and Benjamini and Yekutieli correction for multiple testing comparing DDX60  wt versus DDX60  E890A transfected cells. ns, non-significant.",
    "ncbi_link": "Fluc: 
DDX60: 55601"
  },
  {
    "caption": "(C, HEK293T  cells stably expressing a  type I IFN  sensitive response element (ISRE) driven Fluc  gene were transfected with increasing amounts of RIG-I, RIG-I in combination with DDX60  wt, or RIG-I  in combination with DDX60  E890A while supplementing with GFP  plasmid to equalize the total amount of DNA transfected. Transfected cells were then treated with either PBS  (negative control) or transfected with LMW poly(I:C). In parallel, untransfected cells were treated with either PBS  (mock), transfected with LMW poly(I:C), or treated with IFN-ß (positive control). Cells were subsequently used for a luciferase assay  to assess ISRE activity (C) Data information: (C) Mean ± SD from at least n=3 biological replicates; *p < 0.05 using unpaired t-test with Welch's correction, ns, not significant using repeated measures one-way ANOVA with Geisser-Greenhouse correction comparing RIG-I transfected vs RIG-I + DDX60  wt or RIG-I + DDX60  E890A transfected cells.",
    "ncbi_link": "Fluc: 
GFP: 
DDX60: 55601
RIG-I: 23586"
  },
  {
    "caption": "D) HEK293T  cells stably expressing a  type I IFN  sensitive response element (ISRE) driven Fluc  gene were transfected with increasing amounts of RIG-I, RIG-I in combination with DDX60  wt, or RIG-I in combination with DDX60  E890A while supplementing with GFP  plasmid to equalize the total amount of DNA transfected. western blot  for analysis of DDX60, RIG-I, ß-actin (loading control), or GAPDH  (loading control) protein products (D). Quantification of DDX60  and RIG-I band intensities relative to ß-actin  are shown below each respective lane in (D). Data information: (D) representative western blot  from (C).",
    "ncbi_link": "Fluc: 
GFP: 
DDX60: 55601
RIG-I: 23586"
  },
  {
    "caption": "(B) Effect of DDX60  on 5' cap (left) or EMCV  IRES (right) driven Fluc  mRNA polysomes. Data information: Mean percent ± SEM of Fluc  mRNA of each fraction relative to Fluc  mRNA in all fractions, from n=3 biological replicates.",
    "ncbi_link": "Fluc: 
DDX60: 55601"
  },
  {
    "caption": "(C) Representative results of RNA electrophoresis  analysis of individual fractions. Shown are results from one replicate of DDX60-transfected, EMCV-IRES-PV-infected cells. RNA  was analyzed by Bioanalyzer to visualize 28S, and 18S ribosome   subunit distribution. RIN, RNA  integrity number.",
    "ncbi_link": "DDX60: 55601"
  },
  {
    "caption": "(D) Effect of DDX60  expression on parental poliovirus (type I IRES, purple circles) versus chimeric poliovirus  (type II IRES, red squares) VP4  mRNA polysomes  (left) and cellular GAPDH   mRNA polysomes  in the same samples. Data information: Mean percent ± SEM of poliovirus VP4  or GAPDH  mRNA in each fraction relative to VP4  or GAPDH   mRNA in all fractions from n=3 replicate plates per condition.",
    "ncbi_link": "VP4: 
DDX60: 55601
GAPDH: 2597"
  },
  {
    "caption": "SUD binds to Paip1 and Paip1M with the same binding intensity. n. s.: not significant.",
    "ncbi_link": "Paip1: 10605"
  },
  {
    "caption": "The Mac2 subdomain is crucial for interacting with Paip1M.",
    "ncbi_link": "Paip1: 10605"
  },
  {
    "caption": "Δ16-Mac2 cannot bind Paip1M, Mac1−2 binds to Paip1M in the split-YFP assay. Scale bars represent 50 µM.",
    "ncbi_link": "Paip1: 10605"
  },
  {
    "caption": "SUD and PABP do not compete with each other for interacting with Paip1. (A) Excess expression of SUD-RFP does not impair the split-YFP signal between PABP and Paip1 (lower images), compared to the control (upper images). (B) Co-expression of excess RFP-PABP does not result in an impaired interaction between Paip1 and SUD either. RFP: red fluorescent protein. Scale bars represent 50 µM.",
    "ncbi_link": "Paip1: 10605"
  },
  {
    "caption": "Left image: SUD generally stimulates protein translation level detected by the luciferase-pcDNA3 reporter (n=6). Middle image: SUD does not increase the amounts of total protein synthesis (host and viral proteins) in the replicon-transfected cells. Right image: SUD augments viral protein synthesis (n=8). HEK-293 cells growing in 12-well plates were transfected with the indicated plasmids and replicon DNA. Twenty-four hours post-transfection, cells were harvested for Renilla luciferase activity measurement (left and right image). For the ribopuromycylation assay, 24 hours post-transfection cells were pulsed with 3 µM puromycin for 1 hour at 37°C before harvesting for western blot analysis (middle image).",
    "ncbi_link": "luciferase: "
  },
  {
    "caption": "(B) Quantitative polymerase chain reaction  (qPCR) analysis of Mmps including Mmp2, Mmp9, Mmp10, Mmp12 and Mmp13 mRNA from mouse peritoneal macrophages stimulated with AG (1 μg/ml) for indicated times. (C) Immunoblots of cell supernatants to analyze secreted MMP2, MMP9, MMP10, MMP12 and MMP13 by mouse peritoneal macrophages stimulated with AG (1 μg/mL) for indicated  times; GADPH of cell lysates served as a loading control. Data information: Data are means + SD averaged from 3 independent experiments performed with technical triplicates and each symbol represents the mean of technical triplicates. Two-way ANOVA followed by Tukey's post hoc test was used for statistical analysis. *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001.",
    "ncbi_link": "Mmp10: 17384
Mmp12: 17381
Mmp13: 17386
Mmp2: 17390
Mmp9: 17395"
  },
  {
    "caption": "(H) qPCR analysis of Mmps including Mmp9, Mmp10, Mmp12, and Mmp13 from mouse peritoneal macrophages infected with H37Rv for 24h (MOI=5) in absence or presence of AG  aptamers (1 μg/ml). (I) Immunoblots  of cell supernatants to analyze secreted MMP9, MMP10, MMP12 and MMP13 by mouse peritoneal macrophages infected with H37Rv for indicated times (MOI=5) in the absence or presence of AG  aptamers (0.5 μg/ml); GADPH of cell lysates served as the loading control. Data information: Data are means + SD averaged from 3 independent experiments performed with technical triplicates and each symbol represents the mean of technical triplicates. Two-way ANOVA followed by Tukey's post hoc test was used for statistical analysis. *, p<0.05; **, p<0.01; ***, p<0.001; ****, p<0.0001.",
    "ncbi_link": "Mmp10: 17384
Mmp12: 17381
Mmp13: 17386
Mmp9: 17395"
  },
  {
    "caption": "(I) Immunoblot of lysates of shCtrl and shGalectin-9 THP-1  cells stimulated with AG (1 μg/ml) for indicated  times. Data are representative of n=3 independent experiments.",
    "ncbi_link": "Galectin-9: 3965"
  },
  {
    "caption": "(K) qRT-PCR detection of MMP transcripts including Mmp9, Mmp10, and Mmp12  in shCtrl and shGalectin-9 THP-1  cells stimulated with AG (1 μg/ml) for 24 h in absence or presence of ERK inhibitor PD98059 (10 μM). Data information: Data are means + SD averaged from 3 independent experiments performed with technical triplicates and each symbol represents the mean of technical triplicates. Two-way ANOVA followed by Dunnett's post hoc test were used for statistical analysis. ns, not significant; *, p<0.05; ***, p<0.001 ****, p<0.0001.",
    "ncbi_link": "Galectin-9: 3965
Mmp10: 4319
Mmp12: 4321
Mmp9: 4318"
  },
  {
    "caption": "(F) Immunoblots of cell lysates of peritoneal macrophages isolated from WT or Galectin-9 KO mice stimulated with AG (1 μg/ml) in absence or presence of  TAK1 inhibitor 5Z-7-OZ (1 μM) for indicated  times. Data are representative of n=3 independent experiments.",
    "ncbi_link": "Galectin-9: 16859"
  },
  {
    "caption": "(B, WT or Galectin-9 KO mice were intraperitoneally treated with AG for 3 d in the absence or presence of the MMP inhibitor marimastat (10 mg/kg) given  intraperitoneally prior to AG  stimulation.  Lung sections  stained with H&E Data information: Data are representative of n=3 independent experiments.",
    "ncbi_link": "Galectin-9: 16859"
  },
  {
    "caption": "(D, WT or Galectin-9 KO mice were intranasally infected with  H37Rv for 4 weeks in absence or presence of intranasally administrated AG aptamers (1 μg) once at a 1 week-interval. Lung sections stained with H&E Data information: Data are representative of n=3 independent experiments.",
    "ncbi_link": "Galectin-9: 16859"
  },
  {
    "caption": "Cells were infected at the indicated multiplicity of infection (MOI) and analyzed after 20h. A. TMPRSS2 increases fusion and cell mortality. Right panel: Areas of GFP+ cells and PI+ cells",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "Cells were infected at the indicated multiplicity of infection (MOI) and analyzed after 20h. B. IFITM1, but not IFITM2 and 3, inhibits SARS-CoV-2-induced syncytia formation. Right panels: Area of GFP+ cells",
    "ncbi_link": "IFITM1: 8519
IFITM2: 10581"
  },
  {
    "caption": "Cells were infected at the indicated multiplicity of infection (MOI) and analyzed after 20h. D. IFITM1 decreases the number of infected cells. Right panel: Fraction of cells positive for S, normalized to control cells (transduced with pQCXIP-empty vector ).",
    "ncbi_link": "IFITM1: 8519"
  },
  {
    "caption": "D. TMPRSS2 accelerates fusion. Cells were monitored by video microscopy and the GFP area was quantified over time. Left panel: one representative experiment. Results are mean±sd from 3 fields per condition. Right panel: Mean±sd from 7 independent experiments (at 12h post transfection).",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "E. Impact of TMPRSS2 and IFITMs on the kinetics of fusion by S-expressing 293T cells. One representative out of three independent experiment is shown.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "A. S-expressing cells (Donor cells), ACE2-expressing cells (Acceptor cells) were co-transfected with TMPRSS2, IFITM or control plasmids. Cell fusion was quantified by measuring the GFP+ area after 18h. The indicated combinations were tested. The impact of IFITMs was measured in absence of TMPRSS2 (left panel), in presence of TMPRSS2 in donor (middle panel) or acceptor cells (right panel). Data are mean±sd of 4 independent experiments. Statistical analysis: One-Way ANOVA, ns: non-significant, ∗∗p < 0.01, ∗∗∗∗p < 0.0001.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "Impact of TMPRSS2 on IFITMs levels. B. TMPRSS2 does not decrease IFITM amounts measured by flow cytometry. 293T cells were transfected with the indicated IFITM plasmids, with or without TMPRSS2, and analyzed 18h later.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "C. Impact of TMPRSS2 on S and ACE2, measured by Western Blot. 293T cells were transfected with or without IFITM1, TMPRSS2, S or ACE2 plasmids, and analyzed 18h later.",
    "ncbi_link": "ACE2: 59272
IFITM1: 8519
TMPRSS2: 7113"
  },
  {
    "caption": "Impact of TMPRSS2 on S levels. D. TMPRSS2 decreases S surface levels, measured by flow cytometry. 293T cells were transfected with S plasmid, with or without TMPRSS2, and analyzed 18h later. Murine polyclonal anti-S antibodies, one serum from a convalescent COVID-19 patient (sera n°111), and two monoclonal antibodies (anti-S1 and anti-S2) were tested. Data are representative of three independent experiments.",
    "ncbi_link": "TMPRSS2: 7113"
  },
  {
    "caption": "I) Quantification of Northern Blot  results. Normalised to GAPDH, n=3, error bars are standard error of the mean. Asterix indicates p-value (*, p<0.05, based on unpaired, 2-tailed t-test).",
    "ncbi_link": "GAPDH: "
  },
  {
    "caption": "G. IncuCyte live-imaging analysis of WT and Casp11-/- BMDM viability  after infection with  M. catarrhalis as in D, or transfection with LPS. Data information: Data are pooled from two (G) independent experiments mean and s.e.m. in G).",
    "ncbi_link": "Casp11: 12363"
  },
  {
    "caption": "A. Immunoblot  analysis of caspase-1 (Casp-1),  caspase-11 (Casp-11) and  gasdermin D (GSDMD) in WT, Nlrp3-/-, Casp11-/- and Aim2-/- BMDMs  left untreated (Med.) or 5 h after transfection with 5 µg of LOS  from M. catarrhalis (O35E) or 5 µg of LPS  from  E. coli. Data information: Data are from three independent experiments (A,",
    "ncbi_link": "Aim2: 383619
Casp11: 12363
Nlrp3: 216799"
  },
  {
    "caption": "F. Transcript abundance for genes encoding GTPases in WT and Ifnar1-/- BMDMs  infected with M. catarrhalis  as in C. Transcript abundance is provided in counts per million (CPM). Data information: Data are pooled from three independent experiments",
    "ncbi_link": "Ifnar1: 15975"
  },
  {
    "caption": "G.  qRT-PCR analysis of genes encoding the family of guanylate binding proteins (GBP1-11) in WT and Ifnar1-/- BMDMs  left untreated (Med.) or following treated as in C. Data information: Each symbol represents an independent biological replicate G). NS, no statistical significance; ** P<0.01; *** P<0.001; **** P<0.0001 (one-way ANOVA with Dunnett's multiple-comparisons test G)). Data are from one experiment representative of four (G) independent experiments (mean and s.e.m. in G).",
    "ncbi_link": "GBP1: 14468
Ifnar1: 15975"
  },
  {
    "caption": "F. Recovery of M. catarrhalis (as colony-forming units (CFU) from primary WT, Gbpchr3-KO and Ifnar1-/- lung fibroblasts  4, 8 and 12 h after infection  with M. catarrhalis (Ne11, MOI 100). Data information: Each symbol represents an independent biological replicate F). NS, no statistical significance; * P<0.05; ** P<0.01; *** P<0.001; **** P<0.0001 (one-way ANOVA with Dunnett's multiple-comparisons test Data are from three independent experiments F; mean and s.e.m.",
    "ncbi_link": "Gbp: 229900///55932///14468///229898///14469
Ifnar1: 15975"
  },
  {
    "caption": "G. Quantitation of intracellular bacteria by Transmission electron microscopy (TEM) in WT, Gbpchr3-KO and Ifnar1-/- BMDMs  infected with M. catarrhalis (Ne11, MOI 50) for 12 h. Each symbol represents an independent experiment (E and F). Data information: A total of 100 BMDMs  were analysed to quantify the intracellular  bacterial burden  using electron microscopy  (G). Data are from one experiment representative of two (G) independent experiments mean and s.e.m.",
    "ncbi_link": "Gbp: 229900///55932///14468///229898///14469
Ifnar1: 15975"
  },
  {
    "caption": "A. Immunoblot  analysis of caspase-1  (Casp-1), caspase-11 (Casp-11) and gasdermin D (GSDMD) in WT, Gbp1-/-, Gbp2-/-, Gbp3-/-, Gbp5-/-, Gbp7-/-, Gbp4/8/9-/-, Gbp11­­-/- and Casp11-/- BMDMs  left untreated (Med.) or assessed 10 h after infection with M. catarrhalis (Ne11, MOI 100), or 5 h after transfection with 5 µg LPS  from E. coli.",
    "ncbi_link": "Casp11: 12363
Gbp11: 634650
Gbp2: 14469
Gbp1: 14468
Gbp3: 55932
Gbp4: 17472
Gbp5: 229898
Gbp7: 229900"
  },
  {
    "caption": "A, B. Bacterial burden  and concentration of IL-18 in the spleen  of WT mice  (n=10) and Casp11-/- mice  (n=10) after M. catarrhalis infection. C, D. Bacterial burden and concentration of  IL-18 in the spleen  of WT mice  (n=10) and Nlrp3-/- mice  (n=11) after  M. catarrhalis infection. E, F.  Bacterial burden  and concentration of  IL-18 in the spleen  of WT mice  (n=10) and Gbp1-/- mice  (n=9) after  M. catarrhalis infection. G, H. Bacterial burden and concentration of IL-18 in the spleen  of WT mice  (n=10) and Gbp2-/- mice  (n=8) after M. catarrhalis infection. I, J.  Bacterial burden and concentration of  IL-18 in the spleen  of WT mice  (n=10) and Gbp3-/- mice  (n=8) after  M. catarrhalis infection. K, L. Bacterial burden and concentration of IL-18 in the spleen  of WT mice  (n=5) and Gbp5-/- mice  (n=8) after M. catarrhalis infection. Data information: A mix of male  and female mice  6-8 weeks old were used in each experiment and were injected i.p. with 2×107 CFU  of M. catarrhalis and analysed after 6 h. Each symbol represents an individual mouse  (A-L). Each panel represents data from a single experiment (mean and s.e.m. in A-L). Each experiment was performed at least two times. * P<0.05; ** P<0.01; *** P<0.001 (two-tailed t-test (A-L)).",
    "ncbi_link": "Casp11: 12363
Gbp2: 14469
Gbp1: 14468
Gbp3: 55932
Gbp5: 229898
Nlrp3: 216799"
  },
  {
    "caption": "(A) Vero GFP-split cells were transfected with variant S proteins and imaged 18h post-transfection. Left Panel: Fusion was quantified by GFP area/ number of nuclei and normalized to D614G for each of the transfected variant S proteins. Right Panel: Representative images of Vero GFP-split cells 18h post-transfection, GFP (Green) and Hoechst (Blue). Top and bottom are the same images with and without Hoechst channel. Scale bars: 200 µm.",
    "ncbi_link": "S proteins: 43740568"
  },
  {
    "caption": "(D) Caco2 GFP-split cells were transfected with variant S proteins and imaged 18h post-transfection. Left Panel: Fusion was quantified by GFP area/ number of nuclei and normalized to D614G for each of the transfected variant S proteins. Right Panel: Representative images of Caco2 GFP-split cells 18h post-transfection, GFP (Green) and Hoechst (Blue). Top and bottom are the same images with and without Hoechst channel. Scale bars: 200 µm",
    "ncbi_link": "S proteins: 43740568"
  },
  {
    "caption": "Representative H&E (top) and immunofluorescent (IF) images (bottom) of control and Lats1/2 dKO airways at indicated time points post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CC10 (for secretory cell, white), Acetylated tubulin (Act-Tub, for ciliated cell, green), and DAPI (blue). Scale bar, 100μm. Statistical quantification of Scgb1a1 lineage-labeled tdTomato+CC10+ secretory cells in (B).",
    "ncbi_link": "Lats1: 16798"
  },
  {
    "caption": "Representative IF images of control and Lats1/2 dKO airways at indicated time points post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CC10 (green), AQP5 (for AT1 cell, white), and DAPI (blue). Scale bar, 100μm. Quantification of Scgb1a1 lineage-labeled tdTomato+AQP5+ AT1 cells in (D). Data are presented as mean ± SEM (n=5 mice for each group).",
    "ncbi_link": "Lats1: 16798"
  },
  {
    "caption": "Representative IF images of control and Lats1/2 dKO airways at indicated time points post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CLDN4 (for DATPs, white), CC10 (G, green), AGER (H, for AT1 cell, green), and DAPI (blue). Quantification of Scgb1a1 lineage-labeled tdTomato+CLDN4+ DATPs in (G and H). Data are presented as mean ± SEM (n=5 mice for each genotype).",
    "ncbi_link": "Lats1: 16798"
  },
  {
    "caption": "Representative H&E and IF images of control, Lats1/2 dKO, and Raptor;Lats1/2 tKO airways at day 21 post tamoxifen treatment. Tomato (for Scgb1a1 lineage, red), CC10 (green, upper), AGER (green, lower), and DAPI (blue). Scale bar, 100μm.",
    "ncbi_link": "Lats1: 16798
Raptor: 74370"
  },
  {
    "caption": "Measurement of L-amino acid or essential amino acids (leucine, isoleucine, valine) contents in Scgb1a1 lineage-labeled tdTomato+ organoids derived from control, Lats1/2 dKO or Raptor;Lats1/2 tKO mice. Data are presented as mean ± SEM (n=3 technical replicates for each genotype). *p<0.05, **p<0.001 (Student's t-test).",
    "ncbi_link": "Lats1: 16798
Raptor: 74370
Scgb1a1: 22287"
  },
  {
    "caption": "Western blot images for the expression of YAP, ATF4, and LAT1/Slc7a5 in control or YAP5SA overexpressed C22 airway epithelial cell line. Knockdown of ATF4 was induced by using lentiviral-mediated inducible scramble shRNA (shScramble, control) or shATF4.",
    "ncbi_link": "ATF4: 11911
YAP5SA: 22601"
  },
  {
    "caption": "Representative H&E images and IF images showing the expression of secretory cell marker CC10, DATP cell marker CLDN4, and AT1 cell marker CAV1 in organoids derived from Lats1/2 dKO secretory cells with shscramble, shAtf4, or shSlc7a5. CC10 (green), CLDN4 (white), CAV1 (white) and DAPI (blue). Quantification of Scgb1a1+ lineage-labeled tdTomato+CC10+ secretory cells (red), tdTomato+CLDN4+ DATP cells (green), and tdTomato+CAV1+ AT1 cells (blue) in (E). Representative H&E images and IF images showing the expression of secretory cell marker CC10, DATP cell marker CLDN4, or AT1 cell marker CAV1 in organoids derived from Scgb1a1 lineage-labeled secretory cells with or without hydroxytamoxifen-induced ATF4 overexpression. CC10 (green), CLDN4 (white), CAV1 (white), and DAPI (blue). Quantification of Scgb1a1 lineage-labeled tdTomato+CC10+ secretory cells (red), tdTomato+CLDN4+ DATP cells (green), and tdTomato+CAV1+ AT1 cells (blue) in (G).",
    "ncbi_link": "Atf4: 11911
ATF4: 11911
Lats1: 16798
Slc7a5: 20539"
  },
  {
    "caption": "(B) Gpr56 transcript levels in isolated microglia from Gpr56 S4 mice.",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(D) Representative images of Nissl staining of Gpr56 null and Gpr56 S4 E16.5 neocortex. Arrows indicate cortical ectopias that are shown in insets. (E) Quantification of ectopia size per section. (F) The distribution of ectopia from rostral to caudal cortex.",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(G). Myelin basic protein (MBP) staining of corpus callosum in P28 controls, Gpr56 null and Gpr56 S4 mice.",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(I) Gpr56 transcript levels in WT microglia at P5 and P14.",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "K) Representative images of vGlut2/Homer1 staining in the dLGN of control, Gpr56 null, and Gpr56 S4 brains at P10. Arrows pointing to the enlarged synapse in the insets. L) Relative vGlut2/Homer1 synapse density in dLGN. N=10 (Ctrl), N=6 (Gpr56 null), N=3 (Gpr56 S4).",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(N) Representative images and surface rendered microglia (green) in which CTB+(red) RGC inputs were engulfed. (O) Quantification of the percentage of engulfed RGC inputs in controls, Gpr56 null and Gpr56 S4 microglia.",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(A) Gpr56 is deleted in CKO microglia. RNAscope shows Gpr56 transcripts co-localize with microglia (arrow) in controls, but not in CKO, and is absent in all cell types in the global Gpr56 KO (Gpr56 null). Arrowhead indicates non-microglia cells expressing Gpr56. RNAscope was performed in the prefrontal cortex of P30 mice. Scale bar, 20 µm. (B) Quantification of Gpr56 fluorescence signals in (A). N = 20-50 cells for each. ",
    "ncbi_link": "Gpr56: 14766"
  },
  {
    "caption": "(G) Baf A1 sensitivity assay for NDST3  KO cells after the NDST3 restoration. The NDST3  KO cells with stable expression of Flag-NDST3 or Flag-EGFP (control) were treated with 25 nM  Baf A1 for 72 h, and cell survival was measured using  calcein AM staining. The cell survival  was calculated as the fluorescence intensity of the treated cells relative to the untreated cells (n = 4 independent cultures, ****P < 0.0001). Data information: Error bars represent ± standard deviation. Scale bar, 200 μm. ",
    "ncbi_link": "EGFP: 
Flag: 
NDST3: 9348"
  },
  {
    "caption": "(C) Lysosomal pH  values in WT and NDST3  KO RPE1  cells calculated from the fluorescence ratio of LysoSensor Yellow/Blue dextran staining against the pH calibration curve in (B) (n = 3 independent cultures, *P = 0.0242). (D) Lysosomal  pH values measured for WT and NDST3 KO  RPE1 cells after the treatment with Baf A1  (100 nM, 1h) (n = 3 independent cultures, *P = 0.0305). Data information: Error bars represent ± standard deviation. Scale bar, 10 μm.",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(F) Magic Red assay for Cat B proteolytic activity. WT and NDST3 KO RPE1 cells were treated with vehicle (VEH) or Baf A1 (100 nM, 1 h) and then stained with MR-(RR)2 to measure the Cathepsin B activity (n = 48 cells in the VEH-treated WT group, n = 37 cells in the VEH-treated NDST3 KO group, n = 64 cells in the Baf A1-treated WT group, n = 42 cells in the Baf A1-treated NDST3  KO group, ****P < 0.0001).",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(G) Alexa Fluor (AF) 488-dextran degradation assay. WT and NDST3 KO  RPE1 cells were loaded with AF488-dextran in culture medium and observed for fluorescence. The AF488  fluorescence signals without a chase period, with a 4-h chase period, and with the 4-h chase period in the presence of Baf A1 (100 nM, 1h) were recorded as fluorescence of uptake, chase, and chase with Baf A1, respectively. The AF488 intensity per cell was quantified and calculated into  degradation percentage according to the equation in Materials and Methods (n = 62 cells in the VEH-treated WT group, n = 36 cells in the VEH-treated  NDST3  KO group, n = 65 cells in the Baf A1-treated WT group, n = 78 cells in the Baf A1-treated NDST3 KO group, ****P < 0.0001).",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(J) The LC3  turnover assay after a 48-h Baf A1 treatment. WT and NDST3 KO  RPE1 cells were cultured with 25 nM Baf A1 for 48 h and analyzed for the LC3B-II  fold change as in (I) (n = 6 independent experiments, **P = 0.0014). Data information: Error bars represent ± standard deviation. Scale bar, 10 μm. ",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(A) To examine the levels of the V-ATPase V1-V0 holoenzyme in WT and NDST3 KO RPE1  cells, cytosolic and membrane fractions were analyzed by immunoblotting  using antibodies against the V-ATPase subunits V1A (ATP6V1A), V1C1 (ATP6V1C1), and V0D (ATP6V0D). LAMP1 and vinculin were used as loading controls for membrane proteins and cytosolic  proteins, respectively. (B) Quantification of the levels of ATP6V0D relative to LAMP1 in the  membrane fraction from (A) (n = 3 independent experiments, P = 0.7786). Data information: Error bars represent ± standard deviation.",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "The assembly of V-ATPase V1-V0 holoenzymes in WT RPE1 cells over-expressing the  α-tubulin deacetylase HDAC6 or EGFP  as a control. Representative  immunoblots for ATP6V0D, ATP6V1A, ATP6V1C1, LAMP1 and GAPDH are shown in (H).",
    "ncbi_link": "EGFP: 
HDAC6: 10013"
  },
  {
    "caption": "(M-O) Loss of  NDST3 enhances microtubule acetylation and the colocalization of the  lysosomes with V-ATPase V1 subunits. WT and NDST3  KO PRE1 cells stably expressing  LAMP1-GFP were fixed and analyzed by  immunofluorescence staining with antibodies against ATP6V1C1 and Ac-α-tubulin. The relative levels of Ac-α-tubulin (N) (n = 75 cells in the WT group, n = 79 cells in the  NDST3 KO group, ****P < 0.0001) and the colocalization of LAMP1-GFP  with  ATP6V1C1 (O) (n = 75 cells in the WT group, n = 79 cells in the NDST3 KO group, ****P < 0.0001) are quantified.",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(C) In vitro enzymatic assay quantitating the effect of NDST3 on α-tubulin acetylation. Flag-NDST3 was expressed in HEK 293 cells and immunoprecipitated by anti-Flag beads. Flag-EGFP was used as a control. The immunoprecipitated  protein was incubated with purified tubulin heterodimers in vitro, with or without 1 mM NAD+, 400 nM TSA, or 5 mM nicotinamide (NAM) for 2 h at room temperature. The reaction products were examined by  immunoblotting against  Ac-α-tubulin or total α-tubulin (n = 3 independent experiments, *P = 0.0185, **P < 0.01, ****P < 0.0001). (D) The same in vitro enzymatic assay as in (C), except that the purified  tubulin  was polymerized in the presence of 20 μM Taxol  and 1 mM GTP (n = 3 independent experiments, **P < 0.01, ***P = 0.0001). Data information: Error bars represent ± standard deviation. ns means non-significant. ",
    "ncbi_link": "Flag: 
NDST3: 9348"
  },
  {
    "caption": "(A, B) NDST3 protein levels relative to β-tubulin in B lymphocytes derived from healthy controls and C9orf72-linked ALS patients, as examined by immunoblotting  (n = 3 biologically independent samples, **P = 0.0026). Data information: Error bars represent ± standard deviation.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(C-F) The protein levels of NDST3 relative to GAPDH (D) (**P = 0.0013), Ac-α-tubulin relative to total α-tubulin (E) (*P = 0.0379), and total α-tubulin relative to GAPDH (F) (P = 0.5700), as examined by immunoblotting, in spinal cord tissues from healthy controls and C9orf72-linked ALS patients (n = 4 biologically independent samples in the control group and n = 5 biologically independent samples in the  ALS patient group). Data information: Error bars represent ± standard deviation.",
    "ncbi_link": "C9orf72: 203228"
  },
  {
    "caption": "(G-I) Immunoblotting assays showing down-regulation of NDST3 in C9orf72 shRNA (shC9orf72)-treated RPE1  cells, as compared to control shRNA (shCTRL)-treated cells. Quantification of C9orf72  and  NDST3 expression relative to  GAPDH is shown in (H) (n = 4 independent experiments, ***P = 0.0004) and (I) (n = 4 independent experiments, ***P = 0.0001), respectively. (J-L) Immunoblotting assays showing up-regulation of NDST3 in  RPE1 cells over-expressing Flag-C9orf72 compared to those expressing Flag-EGFP as control. Quantification of C9orf72  and NDST3 expression  relative to GAPDH is shown in (K) (n = 3 independent experiments, **P = 0.0011) and (L) (n = 3 independent experiments, **P = 0.0033), respectively. Data information: Error bars represent ± standard deviation.",
    "ncbi_link": "EGFP: 
Flag: 
C9orf72: 203228"
  },
  {
    "caption": "(M, N) Baf A1 sensitivity assay for WT,  NDST3 KO, and Noco-treated NDST3 KO  RPE1 cells expressing proline-arginine poly-dipeptide (PR82). 24 h after the transfection of  PR82, WT and NDST3  KO cells were treated with vehicle or 10 μg/mL Noco overnight. The cell survival measured using calcein AM staining at 48 h post-transfection was quantified as the percentage of the fluorescence intensity for treated cells relative to that of untreated cells (n = 3 independent cultures, *P = 0.0369, ***P = 0.0007). Scale bar, 200 μm. Data information: Error bars represent ± standard deviation.",
    "ncbi_link": "NDST3: 9348"
  },
  {
    "caption": "(D) LCL1.11 cells were transfected with siRNA specific for Atg12 or GFP, and Atg12 mRNA levels were determined 24 h later by qPCR. The relative amount of Atg12 mRNA was reduced approximately fourfold.",
    "ncbi_link": "GFP: 
Atg12: 9140"
  },
  {
    "caption": "(E) At 24 h after siRNA transfection, NeoR and NucNeoR were expressed in these cells and antigen presentation was assessed 36 h later. In cells transfected with Atg12 siRNA, but not in mock‐transfected cells or cells transfected with GFP siRNA, antigen presentation of both NeoR and NucNeoR was greatly reduced.",
    "ncbi_link": "GFP: 
Atg12: 9140"
  },
  {
    "caption": "(D) YFP-LC3 and mCherry-Parkin stably expressing TBC1D15−/− cells in the absence or presence of HA-tagged TBC1D15 WT or Δ221-250 mutant were treated with valinomycin for 3 hr. Cells were subjected to immunofluorescence microscopy with anti-HA antibody. Scale bars, 10 μm. (E) The YFP-LC3 morphology of cells in (D) was quantified. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each well.",
    "ncbi_link": "TBC1D15: 64786"
  },
  {
    "caption": "(F and G) YFP-LC3 and mCherry-Parkin stably expressing WT (F) and TBC1D15−/− (G) cells were treated with valinomycin for 3 hr and then subjected to immunoelectron microscopy with anti-GFP antibody. The square in panel a shows enlarged areas in panel b Scale bars, 500 nm.",
    "ncbi_link": "TBC1D15: 64786"
  },
  {
    "caption": "(A) The indicated cells stably expressing YFP-LC3 and mCherry-Parkin were treated with valinomycin for 3 hr followed by immunofluorescence microscopy with anti-Cytochrome c antibody. Confocal images were acquired as z-stacks comprising 6 sequential sections with 0.8 μm z-intervals. Scale bars, 10 μm.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(B) TBC1D15−/− cells prepared as in (A) were subjected to immunoelectron microscopy with anti-GFP antibody. White arrowheads indicate YFP-LC3-labeled tubules. High magnification image is shown in the lower panel. Scale bars, 500 nm.",
    "ncbi_link": "TBC1D15: 64786"
  },
  {
    "caption": "(C) The indicated cells prepared as in (A) were subjected to immunostaining with anti-Tubulin antibody. YFP-LC3 and Tubulin staining are merged in the right panels. Magnified images are shown for TBC1D15−/− cells. Scale bars, 10 μm.",
    "ncbi_link": "TBC1D15: 64786"
  },
  {
    "caption": "(A and B) YFP-Parkin stably expressing cells were treated with valinomycin for indicated times. Total cell lysates were subjected to immunoblotting. I and II denote cytosolic and lipidated LC3B, respectively. An asterisk indicates ubiquitinated TOMM20. (C) Indicated protein amounts as in (B) were quantified. The amount of protein without valinomycin treatment was set to 100%. The error bars represent ±SD from three independent experiments.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(D) YFP-Parkin stably expressing WT HCT116 cells were treated with or without valinomycin for 40 hr. Total cell lysates were analyzed by immunoblotting.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(A) WT, MFF−/− or DRP1−/− cells stably expressing YFP-LC3 and mCherry-Parkin were treated with valinomycin for 3 hr and subjected to immunofluorescence microscopy with anti-TOMM20 antibody. Scale bars, 10 μm. (B) Quantification of mCherry-Parkin translocation to mitochondria after 3 hr of valinomycin treatment. Partial and complete denote that Parkin translocates to some of and all mitochondria, respectively. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each replicate. (C) YFP-LC3 morphologies of cells in (A) were quantified. Percentages of cells harboring diffuse, punctate or accumulated YFP-LC3 are shown. The error bars represent ±SD from three independent replicates. Over 100 cells were counted in each replicate.",
    "ncbi_link": "DRP1: 10059
MFF: 56947"
  },
  {
    "caption": "(D) WT, FIS1−/−, and TBC1D15−/− cells stably expressing YFP-LC3 were grown in starvation media. Z-stacks of confocal images are shown. Scale bars, 20 μm. (E) The number of YFP-LC3 dots in cells under growth or starvation conditions was quantified. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each well.",
    "ncbi_link": "FIS1: 51024
TBC1D15: 64786"
  },
  {
    "caption": "(A) TBC1D15−/− cells and those stably expressing HA-TBC1D15 WT and HA-TBC1D15 (Δ221-250), and FIS1−/− cells stably expressing HA-TBC1D15 WT were subjected to immunostaining with anti-TOMM20 and anti-HA antibodies. Scale bars, 10 μm.",
    "ncbi_link": "FIS1: 51024
TBC1D15: 64786"
  },
  {
    "caption": "(B) HA-TBC1D15 WT or HA-TBC1D15 (Δ221-250) with or without Fis1 was transiently overexpressed (OE) in HeLa cells. Cells were subjected to immunostaining with anti-HA and anti-Fis1 antibodies. Scale bars, 20 μm.",
    "ncbi_link": "Fis1: 51024
TBC1D15: 64786"
  },
  {
    "caption": "(C) YFP-TBC1D17 together with pcDNA vector or Fis1 was transiently overexpressed (OE) in HeLa cells. Cells were subjected to immunostaining with anti-Fis1 and anti-Cytochrome c antibodies. Scale bars, 20 μm.",
    "ncbi_link": "Fis1: 51024"
  },
  {
    "caption": "(D) YFP or YFP-Fis1 was co-overexpressed with HA-TBC1D15 or HA-TBC1D17 in HEK293 cells. The cell extracts were subjected to pull down assays with GFP-Trap. 5% input and bound fractions were analyzed by immunoblotting with anti-HA (upper panel) and anti-GFP (lower panel) antibodies.",
    "ncbi_link": "Fis1: 51024
TBC1D15: 64786
TBC1D17: 79735"
  },
  {
    "caption": "(E) YFP, YFP-TBC1D15, or YFP-TBC1D17 was co-overexpressed with HA-TBC1D15 (upper panel) or HA-TBC1D17 (lower panel) in HEK293 cells. The cell extracts were subjected to pull down assays with GFP-Trap. 5% input and bound fractions were analyzed by immunoblotting with anti-GFP and anti-HA antibodies.",
    "ncbi_link": "TBC1D15: 64786
TBC1D17: 79735"
  },
  {
    "caption": "(F) HA-TBC1D15 (Δ221-250) together with Fis1 and YFP-TBC1D15 WT or YFP-TBC1D17 WT were transiently overexpressed (OE) in HeLa cells. Cells were subjected to immunostaining with anti-HA and anti-Fis1 antibodies. Images of HA and Fis1 staining were merged in the right panels. Scale bars, 20 μm.",
    "ncbi_link": "Fis1: 51024
TBC1D15: 64786"
  },
  {
    "caption": "(B) YFP-TBC1D15 overexpressed in HEK293 cells was subjected to binding assays with GST-fused proteins (GABA, L1, and L2 represent GABARAP, GABARAPL1, and GABARAPL2, respectively). 5% input and bound fractions were analyzed by immunoblotting with anti-GFP antibody (upper panel). Coomassie brilliant blue (CBB) staining shows GST-fusion proteins in bound fractions (lower panel). (C) Binding assay carried out as in (B) with GST-GABARAPL1 WT (GST-WT) or its Y49A/L50A mutant (GST-YL). Immunoblotting with anti-GFP antibody (upper panel) and CBB staining (lower panel) are shown.",
    "ncbi_link": "GABARAPL1: 23710"
  },
  {
    "caption": "(E-H) The indicated YFP-tagged TBC1D15 full-length, truncated, or point-mutant protein or YFP-Fis1 overexpressed in HEK293 cells were subjected to binding assays with recombinant GST-GABARAPL1. 5% input and bound fractions were analyzed by immunoblotting with anti-GFP antibody (upper panel) and CBB staining (lower panel).",
    "ncbi_link": "Fis1: 51024
TBC1D15: 64786"
  },
  {
    "caption": "(J) LC3-LC3 and mCherry-Parkin stably expressing TBC1D15−/− cells in the presence of HA-tagged TBC1D15 WT or F280A mutant were treated with valinomycin for 3 hr. Cells were subjected to immunofluorescence microscopy with anti-HA antibody. Scale bars, 10 μm. (K) The YFP-LC3 morphology of cells in (J) was quantified. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each well.",
    "ncbi_link": "Parkin: 5071
TBC1D15: 64786"
  },
  {
    "caption": "(A) Total cell lysates from HCT116 treated with control (NTC) or RAB7A siRNA were analyzed by immunoblotting.",
    "ncbi_link": "RAB7A: 7879"
  },
  {
    "caption": "(B) The indicated cells stably expressing YFP-LC3 (green) and mCherry-Parkin were treated with control (NTC) or Rab7_#5 siRNA. After 3 hr valinomycin treatment, cells were analyzed by immunofluorescence microscopy with anti-TOMM20 antibody (red). Z-stacks of confocal images are shown. Magnified images are also shown. Scale bars, 10 μm. (C) YFP-LC3 morphologies of cells in (B) were quantified. Percentages of cells harboring diffuse, punctuate or accumulated/tubulated YFP-LC3 are shown. Data and error bars were obtained from at least 50 cells in each of three independent replicates.",
    "ncbi_link": "Parkin: 5071
Rab7: 7879"
  },
  {
    "caption": "(D) The indicated cells stably expressing YFP-LC3 (green), mCherry-Parkin, and 2HA-Rab7 (Red) were treated with or without valinomycin for 3 hr and analyzed by immunofluorescence microscopy with anti-HA antibody. Magnified images are also shown. Scale bars, 10 μm.",
    "ncbi_link": "Parkin: 5071"
  },
  {
    "caption": "(E) YFP-LC3 and mCherry-Parkin stably expressing TBC1D15−/− cells in the presence of HA-tagged TBC1D15 WT or the D397A mutant were treated with valinomycin for 3 hr. Cells were subjected to immunofluorescence microscopy with anti-HA antibody. Scale bars, 10 μm. (F) The YFP-LC3 morphology of cells in (E) was quantified. The error bars represent ±SD from three independent replicates. Over 50 cells were counted in each replicate.",
    "ncbi_link": "Parkin: 5071
TBC1D15: 64786"
  },
  {
    "caption": "D. EMSA showing a differential binding of WT Oct4 and Oct6 POU domains as well as mutated Oct4151M and Oct6151S POU domains on MORE (OctOct) element. The free DNA and DNA bound by monomer or dimer are indicated.",
    "ncbi_link": "Oct6: 5453
Oct4: 18999"
  },
  {
    "caption": "E. EMSA showing binding of WT Oct4 and Oct6 POU domains as well as mutated Oct4151M and Oct6151S POU domains to SoxOct element in the absence or presence of the Sox2 HMG. The free DNA and DNA bound by monomers or dimer are indicated. Quantifications of cooperativity measurements are shown in Fig. EV3C.",
    "ncbi_link": "Oct6: 18991
Oct4: 18999"
  },
  {
    "caption": "F. Bar plot based on single tube EMSAs using cy5-SoxOct and FAM-MORE DNA elements showing the difference in DNA-binding of WT Oct4, WT Oct6, Oct4151M and Oct6151S POU domains. The mean log2 ratio of cy5 (heterodimer) and FAM (homodimer) band intensities are depicted with standard deviation (n=9). Individual data points are shown as gray jitter plots. Tukey multiple comparisons of means was performed to assess significance (*** p < 0.001, ** p < 0.01, * p < 0.05, p > 0.05 n.s.). Compare to Fig. EV1D and EV3D.",
    "ncbi_link": "Oct6: 18991
Oct4: 18999"
  },
  {
    "caption": "D. GFP-positive colonies of mouse iPSCs generated by Oct4 mutants in combination with Sox2, Klf4, and c-Myc. Colonies were imaged 16 days after second viral infection, using a fluorescence microscope. Scale bars: 250 μm; objective 10x.",
    "ncbi_link": "Klf4: 16600
c-Myc: 17869
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "B. Oct4-GFP-positive colonies of two O6SKM iPSC lines, expanded from single colonies of pluripotent cells that were generated by the contribution of the synthetic Oct6 molecule (Oct67K,22T,LinkO4,151S). Scale bars: 250 μm.",
    "ncbi_link": "Oct6: 18991"
  },
  {
    "caption": "C. Genotyping of two O6SKM iPSC lines. Two stable lines of iPSCs generated with the Oct6, Sox2, Klf4, and c-Myc retroviral set are positive for these four transgenes but negative for the Oct4 transgene. OSKM iPSCs and OG2-MEFs were used as PCR controls.",
    "ncbi_link": "Klf4: 16600
c-Myc: 17869
Oct6: 18991
Oct4: 18999
Sox2: 20674"
  },
  {
    "caption": "F. Bisulfite sequencing of genomic Oct4, Nanog, and Col1a1 promoter regions of O6SKM iPSCs, OSKM iPSCs, and OG2-MEFs. White and black circles represent unmethylated and methylated CpG sites, respectively.",
    "ncbi_link": "Col1a1: 12842
Nanog: 71950
Oct4: 18999"
  },
  {
    "caption": "B) Baseline QT interval (top), baseline RR interval (middle), and baseline QT interval corrected with the Bazett's formula (bottom). Bar graphs are divided by isogenic pairs (LQT1R594Q and JLNSR594Q, left; LQT2corr, LQT2N996I, hESCWT, and hESC-LQT2N996I, middle; LQT1corr and LQT1R190Q, right) and in each graph the unrelated WT is shown as a comparison. N: 17-53. * = p<0.05. The colour of the symbol indicates comparisons and relative statistical significance.",
    "ncbi_link": "JLNS: 3753
LQT2: 3757
LQT1: 3784"
  },
  {
    "caption": "A) Representative MEA trace (left) showing the effect of increasing concentrations of LUF7346 on FP contour, measured in LQT2N996I-CMs. Average data (right) showing the effect of LUF7346 on QT interval duration relative to baseline in CMs derived from all the hiPSC lines used in this study. * = p<0.05 vs baseline. Colour in the heatmap defines the magnitude of QT shortening (blue) after treatment with increasing concentrations of LUF7346. N: 7-14.",
    "ncbi_link": "LQT2: 3757"
  },
  {
    "caption": "B) Representative AP from LQT2corr-, LQT2N996I-, LQT1corr-, and LQT1R190Q-CMs paced at 1 Hz, under baseline conditions (black) and after application of increasing concentrations of LUF7346 (colour-code is shown).",
    "ncbi_link": "LQT2: 3757
LQT1: 3784"
  },
  {
    "caption": "C) Effect of LUF7346 on APD90, APD70, and APD50, measured in LQT2corr- (blue), LQT2N996I- (green), LQT1corr- (purple), LQT1R190Q- (dark blue) paced at 1 Hz; * = p<0.05 vs baseline. The colour of the asterisk indicates comparisons and respective statistical significance. ° = p<0.05 vs the genetically-matched corrected control. # = p<0.05 LQT1corr vs LQT2corr. N: 12-15.",
    "ncbi_link": "LQT2: 3757
LQT1: 3784"
  },
  {
    "caption": "D) Effect of LUF7346 on APA and Ediast, measured in LQT2corr- (blue), LQT2N996I- (green), LQT1corr- (purple), and LQT1R190Q-CMs (dark blue) paced at 1 Hz. N: 12-15.",
    "ncbi_link": "LQT2: 3757
LQT1: 3784"
  },
  {
    "caption": "A) Representative MEA trace (left) showing the effect of 100 nM AST and increasing concentrations of LUF7346 in the presence of AST on FP contour, measured in LQT1R594Q-CMs. Average data (right) of the effect of AST and LUF7346 in the presence of AST on QT interval duration compared to baseline in CMs derived from all the hiPSC lines used in this study. * = p<0.05 vs respective baseline. ° = p<0.05 vs AST. Colour in the heatmap defines the magnitude of QT prolongation (red) and QT shortening (blue), respectively, after treatment with AST and with increasing concentrations of LUF7346 in the presence of AST. N: 5-10.",
    "ncbi_link": "LQT1: 3784"
  },
  {
    "caption": "B) Representative AP from WT-, LQT1R594Q- and JLNSR594Q-CMs, paced at 1 Hz, under baseline conditions (black), after application of 100 nM AST (red), and after addition of increasing concentrations of LUF7346 in the presence of AST (colour-code is shown).",
    "ncbi_link": "JLNS: 3753
LQT1: 3784"
  },
  {
    "caption": "C) Effect of AST and LUF7346 in the presence of AST on APD90, APD70, and APD50 in WT- (grey), LQT1R594Q- (red) and JLNSR594Q-CMs (black) paced at 1 Hz. * = p<0.05 vs respective baseline; ° = p<0.05 vs AST. N: 11-16.",
    "ncbi_link": "JLNS: 3753
LQT1: 3784"
  },
  {
    "caption": "D) Effect of AST and LUF7346 in the presence of AST on APA and Ediast in WT- (grey), LQT1R594Q- (red) and JLNSR594Q-CMs (black) paced at 1 Hz. N: 11-16.",
    "ncbi_link": "JLNS: 3753
LQT1: 3784"
  },
  {
    "caption": "A: Representative AP traces measured in JLNSR594Q-CMs paced at 1 Hz, under baseline conditions (black) and after application of either AST alone (red), AST+LUF7346 3 µM (green) and AST+LUF7346 5 µM (blue).",
    "ncbi_link": "JLNS: 3753"
  },
  {
    "caption": "(A) Detection of VgpA in supernatants from indicated strains by immunoblotting (IB) with anti-VgpA antisera.",
    "ncbi_link": "VgpA: "
  },
  {
    "caption": "(B) T3SS2 translocation of VgpA into Caco-2 cells using CyaA-based assay; VopV is a known T3SS2 effector. Error bars represent mean ± standard deviation (n=3 biologically independent experiments).",
    "ncbi_link": "CyaA: 
T3SS2: "
  },
  {
    "caption": "(C) Localization of translocated VgpA (upper panel) and VgpAL10A (lower panel) during infection.",
    "ncbi_link": "VgpA: "
  },
  {
    "caption": " (D) Localization of VgpA (upper panel) or in VgpAL10A (lower panel) in HeLa cells after transfection. EBP2 was detected with anti-EBP2 antibody (red), VgpA and VgpAL10A were detected with anti-VgpA sera (green) and nuclei were stained with DAPI (blue). White arrows indicate co-localization of EBP2 and VgpA (upper panel). VgpAL10A localizes primarily to the nucleoplasm (white arrow, lower panel).",
    "ncbi_link": "VgpA: "
  },
  {
    "caption": " (B) Fluorescence micrographs of Caco-2 cells transfected with siRNA targeting EBP2 (siEBP2) or control siRNA (siNC) and subsequently infected with vopZ'ΔvscN1. Cells were stained with anti-BrdU antibody (green) and DAPI (blue). ",
    "ncbi_link": "vopZ: 
vscN1: 
EBP2: 10969"
  },
  {
    "caption": " (D) The percentage of BrdU+ cells was analyzed as above for cells treated with siNC or siEBP2. Error bars represent mean ± standard deviation (n=3 biologically independent experiments). Two-way ANOVA was used for statistical analysis. *P<0.05 (when compared to siNC-transfected cells that are infected with vopZ'ΔvscN1). ",
    "ncbi_link": "vopZ: 
vscN1: 
EBP2: 10969"
  },
  {
    "caption": " (E) Immunoblot of EBP2 and Actin in Caco-2 cells transfected with siEBP2 or siNC. ",
    "ncbi_link": "EBP2: 10969"
  },
  {
    "caption": " (A) Localization of c-Myc in uninfected Caco-2 cells (first row), Caco-2 cells infected with V. parahaemolyticus vopZ'ΔvscN1 (wild type VgpA, second row), Caco-2 cells infected with vopZ'ΔvscN1vgpA' (third row), Caco-2 cells infected with vopZ'ΔvscN1vgpA':pvgpA (fourth row) and Caco-2 cells infected with vopZ'ΔvscN1vgpA':pvgpAL10A (fifth row). Fixed cells were stained with DAPI (blue), and anti-EBP2 (red), and anti c-Myc (green) antibodies. White arrows are examples indicating the co-localization of EBP2 and c-Myc. ",
    "ncbi_link": "VgpA: 
vgpA: 
vopZ: 
vscN1: "
  },
  {
    "caption": " (B) Amounts of rRNA in uninfected or infected Caco-2 cells transfected with control (siNC) or EBP2-targeting (siEBP2) siRNAs. *P<0.05 (when compared to the siNC-transfected cells that are infected with vopZ'ΔvscN1). ",
    "ncbi_link": "vopZ: 
vscN1: 
EBP2: 10969"
  },
  {
    "caption": " (C) Amounts of RNA polymerase I (POLR1A) were from uninfected Caco-2 cells or cells infected with indicated strains. *P<0.05 (when compared to the uninfected Caco-2 cells). ",
    "ncbi_link": "POLR1A: 25885"
  },
  {
    "caption": " (A) VgpA (upper panel: animals infected with WT) and VgpAL10A (lower panel: animals infected with vgpAL10A) localization in intestinal epithelial cells of infected animals. Arrows in upper panel indicate VgpA localized as punctae in the nucleus; the arrow in the lower panel indicates VgpAL10A localized diffusively in the nucleoplasm. ",
    "ncbi_link": "VgpA: 
vgpA: "
  },
  {
    "caption": " (B) VgpA and VgpAL10A interactions with EBP2 in intestinal epithelial cells isolated from infant rabbits infected with WT or vgpAL10A V. parahaemolyticus. Inputs represent proteins detected in intestinal epithelial cells of uninfected rabbits or rabbits infected with the indicated strains. Outputs represent eluates from protein A/G beads cross-linked with anti-EBP2 (IP: anti-EBP2) or anti-VgpA (IP: anti-VgpA) antibodies and analyzed with anti-VgpA and anti-EBP2 antibodies. ",
    "ncbi_link": "vgpA: "
  },
  {
    "caption": " (D) Eighteen hours after infant rabbits were infected with WT (middle panel) or vgpAL10A (lower panel) V. parahaemolyticus, fixed sections from the small intestine were stained with antibodies to c-Myc (green), EBP2 (red), and DAPI (blue). Uninfected rabbits were processed similarly and were included as a control (upper panel). White arrows indicate co-localization of c-Myc and EBP2 (middle panel). ",
    "ncbi_link": "vgpA: "
  },
  {
    "caption": "(B) Boxplots summarizing the expression of INHBB, TGFB1 and TGFB3 ligands of the TGFβ/Activin pathway in the different groups of MB (blue WNT, red SHH, yellow Group 3 and green Group 4) and in fetal and adult cerebellum (grey) in the dataset of \"Data ref: Cavalli et al, 2017\". Wilcoxon rank-sum tests were performed to determine p-values for panel B. p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.",
    "ncbi_link": "INHBB: 3625
TGFB1: 7040
TGFB3: 7043"
  },
  {
    "caption": "(D) RT-qPCR were performed on RNA extracted from non-Group 3 (blue) and Group 3 (yellow) MB cell lines to compare expression levels of INHBB (left) and TGFB3 (right). The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "INHBB: 3625
TGFB3: 7043"
  },
  {
    "caption": "(D) RT-qPCR were performed on total RNA extracted from 1603MED cells 48 hours after transfection with siRNA targeting INHBB. Relative INHBB expression was assessed. siCTRL condition was set at 1. The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "INHBB: 3625"
  },
  {
    "caption": "The level of phosphorylated Smad2 (P-Smad2) and total Smad2 (Smad2) was assessed by immunoblotting and β-actin was used as a loading control. Lower bar graphs show WB quantification of P-Smad2 (P-S2) normalized to β-actin. (E) 1603MED cells were transfected with the indicated control siRNA (siCTRL, blue) or targeting INHBB (siINHBB, red). Lysates were prepared 48 hours after transfection. Lower bar graphs represent the quantification of the relative level of P-Smad2 (P-S2) to β-actin. The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "INHBB: 3625"
  },
  {
    "caption": "(F) Growth curve of 1603MED cells after transfection with either siCTRL (blue) or siINHBB (red). The p-values were determined by unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "INHBB: 3625"
  },
  {
    "caption": "(A) Ranking of top genes whose expression is correlated with INHBB in Group 3 MB patient samples. Spearman's rank correlation coefficient ρ and p-value are indicated. The p-values were determined by Spearman rank correlation test *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "INHBB: 3625"
  },
  {
    "caption": "(C) Scatter plot of INHBB and PMEPA1 gene expression levels in all MB groups. Colored dots represent each patient samples and colors represent the MB groups (WNT in blue, SHH in red, Group 3 in yellow and Group 4 in green). The p-values were determined by Spearman rank correlation test *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "INHBB: 3625
PMEPA1: 56937"
  },
  {
    "caption": "Immunoblot analysis of PMEPA1 levels in 1603MED (G) cells 48 hours after transfection with either siCTRL (blue) or siPMEPA1 (red). Bar graphs on the right represent the quantification of the relative level of PMEPA1 protein level normalized to β-actin. The p-values were determined by unpaired t-test *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "PMEPA1: 56937"
  },
  {
    "caption": "Growth curves of 1603MED (H) cells after transfection with either siCTRL (blue) or siPMEPA1 (red). The p-values were determined by two-way ANOVA *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PMEPA1: 56937"
  },
  {
    "caption": "Immunoblot analysis of PMEPA1 levels in D283 (I) cells 48 hours after transfection with either siCTRL (blue) or siPMEPA1 (red). Bar graphs on the right represent the quantification of the relative level of PMEPA1 protein level normalized to β-actin. The p-values were determined by unpaired t-test *p < 0.05, **p < 0.01, ***p < 0.001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "PMEPA1: 56937"
  },
  {
    "caption": "Growth curves of D283 (J) cells after transfection with either siCTRL (blue) or siPMEPA1 (red). The p-values were determined by two-way ANOVA *p < 0.05, **p < 0.01, ***p < 0.001.",
    "ncbi_link": "PMEPA1: 56937"
  },
  {
    "caption": "(B) Expression of INHBB in Group 3 MB cell lines and PDXs relative to HDMB03 (set at 1) by RT-qPCR. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "INHBB: 3625"
  },
  {
    "caption": "(D) Boxplots representing the expression level of INHBB, PMEPA1, MYC and NRL in the different MB subtypes, as defined in Cavalli et al. (Cavalli et al., 2017). Only p-values corresponding to comparisons between Group 3 subtypes are indicated. Patient samples are colored by subtypes as indicated. (E) Scatter plot of INHBB and PMEPA1, expression levels in Group 3 patient samples. Colored dots represent each patient sample and colors represent the group 3 MB subtypes (α in yellow, β in brown and δ in orange). Wilcoxon rank-sum tests were performed for panel D. Spearman's rank correlation coefficient ρ and p-value are indicated on panel E. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. Bars represent the mean ± SD. Number of replicates is n≥3.",
    "ncbi_link": "INHBB: 3625
MYC: 4609
NRL: 4901
PMEPA1: 56937"
  },
  {
    "caption": "RT-PCR assays towards viral RNA extracted by different pcMNPs-based methods.RT-PCR assays amplifying (A) the ORF1ab region and (B) the N gene in pseudoviral RNA extracted by a manual protocol.",
    "ncbi_link": "N gene: 43740575
ORF1ab: 43740578"
  },
  {
    "caption": "RT-PCR assays amplifying the ORF1ab region in pseudoviral RNA extracted by automated protocol, and (B) RT-PCR assays amplifying the N gene in pseudoviral RNA extracted by an automated protocol.",
    "ncbi_link": "N gene: 43740575
ORF1ab: 43740578"
  },
  {
    "caption": "RT-PCR assays amplifying the N gene in pseudoviral RNA following the Conventional RT-PCR protocol, and (B) corresponding calibration curve.",
    "ncbi_link": "N gene: 43740575"
  },
  {
    "caption": "RT-PCR assays amplifying the N gene in pseudoviral RNA following the Direct RT-PCR protocol, and (D) corresponding calibration curve. The red line is the linear regression fit (R2 = 0.998).",
    "ncbi_link": "N gene: 43740575"
  },
  {
    "caption": "C) and D) STAT3 knockdown in BCE cells. BCE cells were transfected with siNegative and siRNAs targeting  STAT3. qRT-PCR were performed to examine STAT3 mRNA levels. STAT3 level in siNegative was set as 1. Data from three independent experiments were averaged and are presented in C. In D, cells transfected with siRNAs were treated with  LIF  (10 ng/ml) or vehicle for 15 minutes. Whole-cell lysates were subjected to  Western blotting with the indicated antibodies. Data information: Bars and error bars represent mean ± SD. All experiments were carried out in three independent studies. Two-way ANOVA was used as statistical test.",
    "ncbi_link": "STAT3: 508541"
  },
  {
    "caption": "E)  LIF-induced  BCE cell growth was abolished by STAT3 knockdown. BCE  cells with STAT3 knockdown were cultured with  LIF (10 ng/ml, Sigma) or vehicle. Cell proliferation was analyzed after 3 days. Fluorescence reading at 590 nm for each vehicle group was set as 1, n=3. siNegative, negative control siRNA not targeting any known genes. Data information: Bars and error bars represent mean ± SD. All experiments were carried out in three independent studies. Two-way ANOVA was used as statistical test. ",
    "ncbi_link": "STAT3: 508541"
  },
  {
    "caption": "E). Knockdown of STAT3 in  BAE  cells. BAE cells were transfected with siRNAs targeting STAT3. In E, cells transfected with siRNAs were treated with LIF (10 ng/ml, Sigma) and vehicle for 15 minutes. Whole-cell lysates were subjected to Western blotting with indicated antibodies.",
    "ncbi_link": "STAT3: 508541"
  },
  {
    "caption": "F). LIF-induced BAE cell growth inhibition was abolished by knockdown of STAT3. BAE cells with  STAT3  knockdown were cultured with LIF (10 ng/ml, Sigma) and vehicle. Cell proliferation was analyzed after 3 days. Fluorescence reading for each vehicle group was set as 1, n=3. Data information: Bars and error bars represent mean±SD. All experiments were carried out in three independent studies. siNegative, negative control siRNA not targeting any known genes. Two-way ANOVA was used as statistical test. ",
    "ncbi_link": "STAT3: 508541"
  },
  {
    "caption": "Violin plots of the log scale normalized expression of LIF receptor subunits, IL6ST (A), LIFR (B), LIF  (C), IL6R (D) in all cell types in the  human choroid  Note the wide distribution of IL6ST (gp130), the common subunit to all receptors of the  IL-6 family (A). In contrast, LIFR is strongly expressed in ECs and to a lesser extent in fibroblasts and pericytes (B). LIF is expressed  in fibroblasts, macrophages/monocytes and pericytes and minimally in  ECs (C). The specific IL-6 receptor (IL6R) is highly expressed in macrophage/monocytes (D), while LIFR has little expression in these cells (B).",
    "ncbi_link": "IL-6: 3569
IL-6 receptor: 3570
IL6R: 3570
gp130: 3572
IL6ST: 3572
LIF: 3976
LIF receptor: 3977
LIFR: 3977"
  },
  {
    "caption": "Violin plots of the log scale normalized  expression of LIF receptor subunits  KDR (E) in all cell types in the human choroid KDR shows, as expected, high  expression selectively in EC (E).",
    "ncbi_link": "KDR: 3791
LIF receptor: 3977"
  },
  {
    "caption": "Figure 1. Extensive identification of Mmi1 RNA targets by combining RNA-IP sequencing and computational approaches. (D) RNA-IPs showing the impact of Mmi1 YTH domain point mutations on Mmi1's binding to ssm4 mRNA. The lower part shows a Western blot monitoring the protein level of WT and mutant Mmi1 proteins in the cells used for the RNA-IPs. Loading was monitored using an anti-Tub1 (tubulin) antibody.",
    "ncbi_link": "ssm4: 2542069"
  },
  {
    "caption": "Figure 2. Mmi1 binding to nam1 lncRNA controls MAPK-mediated entry into sexual differentiation. (E) Mmi1 RNA-IPs showing the specific loss of binding of Mmi1 to nam1-1 lncRNA but not to mei4 mRNA, another target of Mmi1.",
    "ncbi_link": "nam1: 
mei4: 2540241"
  },
  {
    "caption": "Figure 2. Mmi1 binding to nam1 lncRNA controls MAPK-mediated entry into sexual differentiation. (F) Mating assay showing the percentage of zygotes formed over time in WT and nam1-1 cells. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) (B, E and F).",
    "ncbi_link": "nam1: "
  },
  {
    "caption": "Figure 2. Mmi1 binding to nam1 lncRNA controls MAPK-mediated entry into sexual differentiation. (G) Western blots showing the level of Flag-Byr2 protein over the first 4 hours of sexual differentiation in WT and nam1-1 cells. Tubulin (Tub1) level was used as a loading control.",
    "ncbi_link": "nam1: "
  },
  {
    "caption": "Figure 2. Mmi1 binding to nam1 lncRNA controls MAPK-mediated entry into sexual differentiation. (H) Microscopy images of WT (h90) cells transformed with an empty plasmid (Control) and nam1-1 cells transformed with either an empty plasmid (Control) or a plasmid expressing Byr2 protein (Byr2), after 24 hours of induction of sexual differentiation. Scale bar, 10 µm.",
    "ncbi_link": "nam1: "
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (A) Northern blots showing nam1 and byr2 RNA levels during the first 4 hours of sexual differentiation. Ribosomal RNAs (rRNAs) stained with ethidium bromide were used as loading controls. Black lines indicate probes used to detect nam1 and byr2 RNAs.",
    "ncbi_link": "nam1: 
byr2: 2540612"
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (B) ChIPs showing the occupancy of the elongating RNAPII (RNAPII-S2P) over nam1-byr2 locus, in WT and nam1-1 cells. RNAPII-S2P was immunoprecipitated with an antibody recognizing the heptameric repeats (present in the C-terminal domain of the polymerase) when it is phosphorylated on its serine 2. Black lines, genomic regions investigated. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (B, C, E and F).",
    "ncbi_link": "nam1: 
byr2: 2540612"
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (C) RT-qPCRs showing the accumulation of nam1 read-through transcripts (RT1-qPCR) and nam1 lncRNAs (RT2-qPCR) in cells with or without the transcription terminator Ttef inserted at the 3' end of nam1 (scheme). Black arrow, primer used for the strand-specific reverse transcription (RT); Black line, location of the region amplified by PCR. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (B, C, E and F).",
    "ncbi_link": "nam1: 
byr2: 2540612"
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (D) Microscopy images of, respectively, WT (h90), nam1-1 and nam1-1-Ttef cells, after induction of sexual differentiation for 24 hours. The percentage of sporulation and iodine vapor assays are shown at the bottom of the images. Scale bar, 10 µm.",
    "ncbi_link": "nam1: "
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (E) RT-qPCRs showing the accumulation of nam1 read-through transcripts in mmi1∆ and rrp6∆ cells. Black arrow and line as in (C). . Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (B, C, E and F).",
    "ncbi_link": "nam1: 
Mmi1: 2539540
mmi1: 2539540
rrp6: 2543630"
  },
  {
    "caption": "Figure 3. Mmi1 promotes transcription termination of nam1 non-coding gene and prevents nam1 read-through transcription from repressing the downstream MAPKKK gene byr2. (F) ChIPs monitoring the enrichment of H3K9me2 over nam1-byr2 locus and mei4 gene in WT and rrp6∆ cells. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (B, C, E and F).",
    "ncbi_link": "nam1: 
byr2: 2540612
mei4: 2540241
rrp6: 2543630"
  },
  {
    "caption": "Figure 4. Mmi1 drives Rrp6-dependent heterochromatin gene silencing at pericentromeric regions. (B) Northern blot showing the level of nam5/6/7 lncRNA population in mmi1-ts3, dcr1∆, clr4∆ single mutant cells and in mmi1-ts3 dcr1∆ and mmi1-ts3 clr4∆ double mutant cells, at the permissive (25ºC) and restrictive (36ºC) temperatures.",
    "ncbi_link": "nam5: 
clr4: 2540825
dcr1: 2538930
Mmi1: 2539540
mmi1: 2539540"
  },
  {
    "caption": "Figure 4. Mmi1 drives Rrp6-dependent heterochromatin gene silencing at pericentromeric regions. (C) RT-PCRs monitoring the accumulation of nam7 lncRNAs and nam7-L read-through transcripts, in the same cells and conditions as in (B). Red arrow heads point to the expected PCR products while the other bands correspond to non-specific PCR products. From the scheme and the agarose gels: black arrows, primers used for the three different reverse transcriptions; black lines and red numbers, expected PCR products of the three different RT-PCRs; M, DNA ladder Markers; tub1, tubulin control.",
    "ncbi_link": "nam7: 
tub1: 
Mmi1: 2539540"
  },
  {
    "caption": "Figure 4. Mmi1 drives Rrp6-dependent heterochromatin gene silencing at pericentromeric regions. (D) RT-qPCRs showing the levels of nam5/6/7 lncRNA population in the double mutant rrp6∆ dcr1∆ cells, relative to the single mutant rrp6∆ and dcr1∆ cells. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (D, E). P value was calculated using a two-tailed Student's t-test.",
    "ncbi_link": "nam5: 
dcr1: 2538930
Rrp6: 2543630
rrp6: 2543630"
  },
  {
    "caption": "Figure 4. Mmi1 drives Rrp6-dependent heterochromatin gene silencing at pericentromeric regions. (E) RNA-IPs showing that Rrp6-Myc13 binds to nam5/6/7 lncRNAs in a Mmi1-dependent manner. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (D, E). P value was calculated using a two-tailed Student's t-test.",
    "ncbi_link": "nam5: 
Mmi1: 2539540"
  },
  {
    "caption": "Figure 5. Mmi1- and RNAi-mediated silencing of pericentromeric DNA transcription alternate during the progression of the cell cycle. (A) ChIPs assessing the localization of Mmi1 to pericentromeric DNA in WT and clr4∆ cells.",
    "ncbi_link": "clr4: 2540825"
  },
  {
    "caption": "Figure 5. Mmi1- and RNAi-mediated silencing of pericentromeric DNA transcription alternate during the progression of the cell cycle. (B) ChIPs showing the localization of Mmi1 (dashed line) and H3K9me2 (black line) to the pericentromeric nam5/6/7 DNA regions during the progression of the cell cycle. Cell synchronization was achieved by using cdc25-ts cells (see experimental procedures for more details). Cell synchronization was monitored by measuring the percentage of cells with a septum (right part).",
    "ncbi_link": "nam5: 
cdc25: 2542632"
  },
  {
    "caption": "Figure 5. Mmi1- and RNAi-mediated silencing of pericentromeric DNA transcription alternate during the progression of the cell cycle. (C) RT-qPCRs monitoring the levels of nam5/6/7 (left part) and dg (middle part) lncRNA populations during the cell cycle. Average fold enrichment is shown with error bars that indicate mean average deviations (n=3) for (A, B and C).",
    "ncbi_link": "dg: 
nam5: 
Mmi1: 2539540"
  },
  {
    "caption": "Figure 5. Mmi1- and RNAi-mediated silencing of pericentromeric DNA transcription alternate during the progression of the cell cycle. (D) RT-PCRs monitoring the accumulation of nam7 lncRNAs and nam7-L read-through transcripts in G2/M and G1/S phases from synchronized cells as in (B). Red arrow heads point to the expected PCR products. The other bands are non-specific PCR products. From the scheme: black arrows, primers used for the reverse transcriptions; black lines and red numbers, regions amplified by PCR.",
    "ncbi_link": "nam7: 
Mmi1: 2539540"
  },
  {
    "caption": "(a) WT and Pgam5 KO MEFs evaluated by TEM. The black arrows indicate mitochondria; (b) TEM analysis after 12 h CCCP treatment; black arrowheads indicate DMS. Inset shows a DMS with an encapsulated mitochondrion. The black arrows indicate mitochondria. Scale bar=0.5 micron;",
    "ncbi_link": "Pgam5: 72542"
  },
  {
    "caption": "(f) Mitochondrial extracts of WT and Pgam5 KO MEFs treated with DMSO (−) or CCCP (+) for 3 h and analysed by immunoblot as above. (Note that mouse PINK1 antibody can only detect the full-length PINK1). Arrow indicates the 63 kDa form of PINK1.",
    "ncbi_link": "Pgam5: 72542"
  },
  {
    "caption": "(g) Hela cells transduced with either nonspecific (NS) or PGAM5 shRNA viruses were treated with CCCP for 3 h, and mitochondrial fractions were immunoblotted for the proteins indicated. Full-length (*63 kDa) and cleaved (#54 kDa) PINK1 are indicated. For f and g, the numbers below indicate the full-length PINK1 band density compared with the first lane that has been set at 1.0",
    "ncbi_link": "PGAM5: 192111"
  },
  {
    "caption": "(h) Confocal micrographs of Hela cells as in g were transfected with PARKIN-YFP (green) plasmid before CCCP treatment, then (i) treated with CCCP for 12 h. Mitochondria were stained with anti-Tomm20 (red) 4',6-diamidino-2-phenylindole stained nucleus was shown in blue. Co-localization was indicated by white colour. Scale bar=10 μm. (j) Quantification of the co-localization percentage of Tomm20 (red) with parkin (green) per cell by Imaris software (n=7 for NS and PGAM5 shRNA group separately. Results are presented as mean and s.d. values and were analysed by the student t-test). All the blots and images are representative of three independent experiments. DMSO, dimethylsulphoxide.",
    "ncbi_link": "PARKIN: 5071
PGAM5: 192111"
  },
  {
    "caption": "(a) Mitochondria from MEFs from Parl WT (+/+) and KO (−/−) mice were treated with the indicated doses of proteinase K (Prot.K) for 30 min on ice and then immunoblotted for the indicated proteins. Full-length and cleaved PGAM5 bands are indicated with arrows.",
    "ncbi_link": "Parl: 381038"
  },
  {
    "caption": "(b) Pgam5 WT and KO MEFs were transduced with either nonspecific (NS) or Parl shRNA and either treated (+) or not (−) with CCCP for 3 h. Mitochondria were then purified and analysed by immunoblot for the indicated proteins.",
    "ncbi_link": "Parl: 381038
Pgam5: 72542"
  },
  {
    "caption": "(c) WT PINK1 as well as kinase dead (KD) or Parkinson's disease-associated PINK1 mutants (C92F, A168P, H271Q, G309D, L347P, G386S, R464H) were co-transfected into HEK293T cells with the same amount PGAM5 (lane 1-9) or GFP (lane 10-18) expression plasmids and total cell lysates were immunoblotting for PINK1, PGAM5 and actin. The ratio of WT full-length (63 kDa) versus cleaved (54 kDa) PINK1 (*/#) is shown.",
    "ncbi_link": "PGAM5: 192111
PINK1: 65018"
  },
  {
    "caption": "(d) Anti-myc immunoprecipitates (IP) of lysates from 293T cells transfected with combinations of myc-tagged PGAM5 and PINK1-V5 with or without CCCP treatment and immunoblotting with anti-PINK1 or anti-myc.",
    "ncbi_link": "PGAM5: 192111
PINK1: 65018"
  },
  {
    "caption": "(e) Four constructs expressing either: (1) no PGAM5 (empty vector) or (2) amino acids 1-98, (3) 1-110 and (4) 98-289 truncated versions of PGAM5 (left panel). Immunoblot of HEK293T cells expressing PINK1-GFP and myc-tagged PGAM5 truncation mutants as indicated with anti-PINK1 or anti-myc for the input proteins as well as the anti-GFP IP (right panel).",
    "ncbi_link": "PGAM5: 192111"
  },
  {
    "caption": "(f) Co-transfection of GFP, WT PGAM5, 2RA mutant (R98A and R104A) or the 2HA mutant (H99A and H105A) with a PINK1 expression plasmid into HEK293T cells and the input cell lysates as well as the anti-myc IP were immunoblotted with antibodies against PINK1, PGAM5 or actin.",
    "ncbi_link": "PGAM5: 192111"
  },
  {
    "caption": "WT PINK1 was expressed in HEK293T cells with or without PGAM5 or a GFP control plasmid after (g) DMSO or (h) CCCP treatment. Cells were permeabilized with digitonin or Triton X-100 separately, followed by treatment with the indicated amounts of trypsin on ice for 30 min. Cell lysates were immunoblotted for PINK1, PGAM5, Tomm20 or HSP60 as indicated. Full-length (*63 kDa) and cleaved (#54 kDa) PINK1 are shown.",
    "ncbi_link": "PGAM5: 192111
PINK1: 65018"
  },
  {
    "caption": "(a) Body weight was measured in 5-month-old and 12-month-old female Pgam5 WT and KO mice.",
    "ncbi_link": "Pgam5: 72542"
  },
  {
    "caption": "High-performance liquid chromatography-electrochemical detection quantitation of (a) striatal DA and its metabolites (b) dihydroxyphenylacetic acid (DOPAC) (c) Homovanillic acid (HVA) and (d) 3MT levels at three different time points (1, 2 and 12-month-old) in Pgam5 WT or KO mice.",
    "ncbi_link": "Pgam5: 72542"
  },
  {
    "caption": "The 18-month-old Pgam5 WT and KO mice received either water as control (n=4), or 5 mg kg−1 L-DOPA and 12.5 mg kg−1 Benserazide (n=5) by intraperitoneal injection. Twenty minutes later, mice were subjected to the open-field test and the centre area time in seconds (s) as well as the centre area distance in centimeters (cm) were measured as described in the Materials and Methods. Graphs show the mean and s.d. values and were analysed by the student t-test, NS, no significance; *P0.05; **P0.01.",
    "ncbi_link": "Pgam5: 72542"
  },
  {
    "caption": "(e) NRK cells grown on the SAMCell were transfected with FAM-RNAi by reverse transfection and the transfection efficiency was monitored by microscopy. Left panel, FAM-RNAi-positive cells; right panel, differential interference contrast (DIC) image of the cells in the left panel.",
    "ncbi_link": "FAM: "
  },
  {
    "caption": "(a) NRK cells stably expressing CFP-LC3; LAMP1-YFP were transfected with nonspecific (NS)- or Cltc (clathrin heavy chain)-RNAi and starved for 12 h. Scale bar, 5 μm. (b) Cells from a were assessed for enlarged autolysosomes after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d.",
    "ncbi_link": "clathrin heavy chain: 54241
Cltc: 54241"
  },
  {
    "caption": "(c) Representative TEM micrographs of nonspecific- or Cltc-RNAi-transfected NRK cells after 12 h of serum starvation. Scale bar, 5 μm.",
    "ncbi_link": "Cltc: 54241"
  },
  {
    "caption": "(a) NRK cell lines stably expressing CFP-LC3; LAMP1-YFP were transfected with nonspecific (NS)- or PIP5K1B-RNAi and starved for 12 h. Scale bars, 5 μm. (b) Cells from a were assessed for enlarged autolysosomes in a blind fashion after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d.",
    "ncbi_link": "PIP5K1B: 309419"
  },
  {
    "caption": "(c) Representative TEM micrographs of nonspecific- or PIP5K1B-RNAi-transfected NRK cells after 12 h of serum starvation. Scale bar, 5 μm.",
    "ncbi_link": "PIP5K1B: 309419"
  },
  {
    "caption": "(i) NRK cell lines stably expressing OSBP-PH-GFP;LAMP1-Cherry were transfected with PIP5K1B-RNAi. At 60 h after transfection, cells were starved for 12 h and analysed by confocal microscopy. Scale bar, 5 μm.",
    "ncbi_link": "PIP5K1B: 309419"
  },
  {
    "caption": "(j) NRK cell lines stably expressing LAMP1-Cherry;clathrin-GFP were transfected with nonspecific- or PIP5K1B-RNAi and starved for 12 h, and then observed by confocal microscopy. Scale bars, 5 μm. The insets in a, h-j represent enlarged regions of interest.",
    "ncbi_link": "PIP5K1B: 309419"
  },
  {
    "caption": "(a) NRK cells stably expressing CFP-LC3;LAMP1-YFP were transfected with nonspecific (NS)- or PIP5K1A-RNAi and starved for 10 h. The insets represent enlarged regions of interest. Scale bar, 5 μm. (b) Cells from a were assessed for the presence of elongated reformation tubules in a blind fashion after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d. (c) Cells from a were assessed for the length of reformation tubules in a blind fashion after starvation and quantified. 50 cells were counted. The average tubule length is indicated above each column. (d) Diagram of reformation tubules. R, radius of main body; L, length. (e) Representative image of reformation tubules in nonspecific- or PIP5K1A-RNAi-transfected cells. The top and bottom panels show two randomly selected images of the respective samples.",
    "ncbi_link": "PIP5K1A: 365865"
  },
  {
    "caption": "(l) NRK cell lines stably expressing LAMP1-Cherry;clathrin-GFP were transfected with nonspecific- or PIP5K1A-RNAi and starved for 8 h. Scale bar, 5 μm. The middle panels show enlarged regions of interest from the upper panels. The distance between clathrin dots on each reformation tubule in the upper panels is shown in diagrammatic form in the lower panels. Black line: reformation tubules; red dot: clathrin. (m) The distance between two clathrin dots on reformation tubules (RTs) in cells from l was accessed in a blind fashion. Twenty-five cells were counted. The average distance between two clathrin dots is indicated above each column. Uncropped images of blots are shown in Supplementary Fig. S6.",
    "ncbi_link": "PIP5K1A: 365865"
  },
  {
    "caption": "(a) NRK cells stably expressing CFP-LC3; LAMP1-YFP were transfected with nonspecific (NS)- or AP2-RNAi and starved for 12 h. Scale bars, 5 μm. (b) Cells from a were assessed for enlarged autolysosomes in a blind fashion after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d.",
    "ncbi_link": "AP2: 306862"
  },
  {
    "caption": "(c) Representative TEM micrographs of nonspecific- or AP2-RNAi-transfected NRK cells after 12 h of serum starvation. Scale bars, 5 μm.",
    "ncbi_link": "AP2: 306862"
  },
  {
    "caption": "(i) NRK cell lines stably expressing LAMP1-Cherry;clathrin-GFP were transfected with nonspecific- or AP2-RNAi and starved for 12 h. Scale bar, 5 μm. The insets in a, c and i represent enlarged regions of interest. (j) Cells from i were analysed for the Pearson's co-localization coefficent (R(r)) by Olympus Fluoview. n = 30 cells from three independent experiments). Error bars indicate the s.d. Uncropped images of blots are shown in Supplementary Fig. S6.",
    "ncbi_link": "AP2: 306862"
  },
  {
    "caption": "(a) NRK cells stably expressing CFP-LC3; LAMP1-YFP were transfected with nonspecific (NS)- or AP4-RNAi and starved for 12 h. Scale bars, 5 μm. (b) Cells from a were assessed for enlarged autolysosomes in a blind fashion after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d.",
    "ncbi_link": "AP4: 360482"
  },
  {
    "caption": "(c) Representative TEM micrographs of nonspecific- or AP4-RNAi-transfected NRK cells after 12 h of serum starvation. Scale bars, 5 μm.",
    "ncbi_link": "AP4: 360482"
  },
  {
    "caption": "(f) NRK cells were transfected with GFP and LAMP1-GFP. At 20 h after transfection, cells were starved for 0 or 8 h, and then collected and analysed by immunoprecipitation (IP) and western blotting (WB) of proteins as indicated, using stably expressed LAMP1-GFP as bait. TCL, total cell lysate.",
    "ncbi_link": "LAMP1: 25328"
  },
  {
    "caption": "The insets in a, c and g represent enlarged regions of interest. (g) NRK cell lines stably expressing LAMP1-Cherry; clathrin-GFP were transfected with nonspecific- or AP4-RNAi and starved for 12 h. Scale bars, 5 μm. (h) Cells from g were analysed for the Pearson's co-localization coefficent (R(r)) by Olympus Fluoview. n = 30 cells from three independent experiments. Error bars indicate the s.d. Uncropped images of blots are shown in Supplementary Fig. S6.",
    "ncbi_link": "AP4: 360482"
  },
  {
    "caption": "(a) NRK cells were transfected with nonspecific (NS)- or Cltc (clathrin heavy chain)-RNAi and starved for 0, 4, 8 or 12 h. Scale bar, 5 mm. Cells were stained with antibodies against LC3. (b) Cells from a were assessed for LC3 puncta in a blind fashion after starvation and quantified. n = 100 cells from three independent experiments. Error bars indicate the s.d.",
    "ncbi_link": "clathrin heavy chain: 54241
Cltc: 54241"
  },
  {
    "caption": "qPCR was performed on gDNA retrieved from each of the metastases, using primers for BRAF and CRAF and normalized on LINE levels. Bars represent the mean of three replicates, error bars indicate standard deviation. The results confirmed that BRAF was amplified in M032R1, M032R2, and M032R5.",
    "ncbi_link": "BRAF: 673
CRAF: 5894"
  },
  {
    "caption": "Validation of T55delinsRT was done by PCR using insertion-specific primers. As a control, primers amplifying exon 2 of MEK1WT were used.",
    "ncbi_link": "MEK1: 5604"
  },
  {
    "caption": "Transfection of pQXCIP-GFP, MEK1-WT, or MEK1-T55delinsRT into HEK293T cells showed that this mutation induces p-ERK and p-RSK.",
    "ncbi_link": "GFP: 
MEK1: 5604"
  },
  {
    "caption": "Validation of expression of pQXCIP-GFP, MEK1WT, or MEK1T55delinsRT in A375 melanoma cells by immunoblotting.",
    "ncbi_link": "GFP: 
MEK1: 5604"
  },
  {
    "caption": "Dose-response curves for A375 melanoma cells expressing GFP, MEK1WT, or MEK1T55delinsRT with indicated doses of BRAF inhibitor vemurafenib, ERK inhibitor SCH772984, or MEK inhibitor trametinib. Error bars indicate standard deviation.",
    "ncbi_link": "GFP: 
BRAF: 673
MEK1: 5604
MEK: 5605///5604
ERK: 5595///5594"
  },
  {
    "caption": "Colony formation assays with A375 melanoma cells, infected with GFP, MEK1WT, or MEK1T55delinsRT-encoding lentivirus, and treated with indicated doses and inhibitors.",
    "ncbi_link": "GFP: 
MEK1: 5604"
  },
  {
    "caption": "Treatment of A375 MEK1T55delinsRT melanoma cells with DMSO (−), 250 nM dabrafenib (D), 10 nM trametinib (T), or a combination (D+T).",
    "ncbi_link": "MEK1: 5604"
  },
  {
    "caption": "A375 melanoma cells expressing GFP, MEK1WT, or MEK1T55delinsRT were injected into immune-deficient mice (n = 8 per group), and after the tumor size of ˜100 mm3 was reached, mice were treated with 30 mg/kg dabrafenib or vehicle. Graphs represent fold change in tumor volume normalized on the tumor volume on the day of the start of the treatment. Error bars indicate standard error of the mean.",
    "ncbi_link": "GFP: 
MEK1: 5604"
  },
  {
    "caption": "gDNA was isolated from another fragment of the tumor resection, and the PCR with the insertion-specific primers was repeated. Primers amplifying exon 2 of MEK1WT were used as an input control.Source data are available online for this figure.",
    "ncbi_link": "MEK1: 5604"
  },
  {
    "caption": "Validation of the BRAF amplification was performed by qPCR on gDNA derived from the PDX, using primers for BRAF and CRAF and normalized on LINE expression. Bars represent the mean of three replicates, error bars indicate standard deviation. The results confirmed that BRAF was amplified in PDX derived from M032R2 and M032R5, but not from M032R1.",
    "ncbi_link": "BRAF: 673
CRAF: 5894"
  },
  {
    "caption": "Presence of the MEK1T55delinsRT was analyzed by PCR using insertion-specific primers. As a control, primers amplifying exon 2 of MEK1WT were used. The insertion was found in M032R1.X1 and M032R4.X1.",
    "ncbi_link": "MEK1: 5604"
  },
  {
    "caption": "A. WT or LAT-deficient Jurkat cells (Jcam2.5) expressing CAR-GFP were stimulated on SLB-coated with OKT3 (anti-TCR antibody) or CD19 (CAR antigen); in both conditions, the lipid bilayers were also coated with ICAM-1 to facilitate cell attachment. TIRF microscopy revealed clustering of Ax647-labeled streptavidin-Biotin-OKT3 or CD19, which serves as a probe for TCR or CAR respectively. Scale bar, 2 µm. B. Quantification of clustering as normalized variance. n = 100 cells. Shown are the mean ± SD. Statistical test: unpaired two-tailed t-test. **** p < 0.0001. ** 0.005 < p < 0.05. ",
    "ncbi_link": "LAT: 27040"
  },
  {
    "caption": "B. WT or LAT-deficient (Jcam2.5) cells expressing the 3rd or 1st generation CAR were stimulated on supported lipid bilayers coated with CD19 and ICAM-1. TIRF microscopy revealed clustering of CAR and Ax647-labeled streptavidin-Biotin-CD19. Scale bar, 2 µm. C. Quantification of clustering level of Ax647-labeled streptavidin-Biotin-CD19. Shown are means ± SD. Clustering is quantified as normalized variance. N = 50 cells for CAR 3rd WT and 1st WT, 63 cells for CAR 3rd lat-, and 51 cells for CAR 1st lat-. **: 0.0005 < p < 0.005. Statistical test: unpaired two-tailed t-test. ",
    "ncbi_link": "LAT: 27040
lat: 27040"
  },
  {
    "caption": "CAR (3rd generation) T cells were plated on supported lipid bilayers coated with CD19 and ICAM-1 and imaged by TIRF microscopy. A. Gads was recruited to CAR microclusters in both the wild-type and LAT-deficient (Jcam2.5) cells. n = 33 or 34 cells. Shown are the means ± SE. n.s., p = 0.58 by unpaired two-tailed t-test. As a control, Gads is not recruited to LAT-deficient cells activated by OKT3. ",
    "ncbi_link": "LAT: 27040"
  },
  {
    "caption": "CAR (3rd generation) T cells were plated on supported lipid bilayers coated with CD19 and ICAM-1 and imaged by TIRF microscopy. B. Phosphorylated SLP76, recognized by an anti-SLP76 pY145 antibody, was enriched in CAR microclusters in both the wild-type and LAT-deficient cells. In contrast, phosphorylated SLP76 was not enriched in TCR microclusters in LAT-deficient cells. n = 50 cells. Shown are the means ± SE. n.s., p = 0.95 by unpaired two-tailed t-test.",
    "ncbi_link": "LAT: 27040"
  },
  {
    "caption": "CAR (3rd generation) T cells were plated on supported lipid bilayers coated with CD19 and ICAM-1 and imaged by TIRF microscopy. C. Actin remodeling was induced in LAT-deficient cells by CD19-, but not OKT3-coated SLB. No ICAM-1 was supplemented to SLB in this experiment to rule out the costimulation of actin via the LFA-1/ICAM-1 pathway. Actin network was revealed by F-tractin-mScarlet. n = 6 cells. Shown are the means ± SD. n.s., p = 0.68, and 0.98 by unpaired two-tailed t-test.",
    "ncbi_link": "LAT: 27040"
  },
  {
    "caption": "A. Cell-cell conjugation assay. Wild-type or Lat-null (J.LAT) Jurkat T cells expressing CAR-GFP were mixed with Raji cells expressing mCherry-CAAX at a 1:1 ratio for 1 hr before being fixed. Three independent experiments were performed and over 90 cells were scored in each experiment. Scale bar: 5 µm.",
    "ncbi_link": "Lat: 27040
LAT: 27040"
  },
  {
    "caption": "LPS-primed Abro1+/+ and Abro1−/− BMDMs were treated with various doses of ATP. CBA analysis of IL-1β (A) in the culture supernatants.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "LPS-primed Abro1+/+ and Abro1−/− BMDMs were treated with various doses of ATP. ELISA of IL-18 (B) in the culture supernatants.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "CBA analysis of IL-1β secretion from Abro1+/+ and Abro1−/− BMDMs transduced with GFP- or ABRO1-GFP-expressing lentiviruses prior to stimulation with LPS and ATP. Cell lysates were immunoblotted with anti-ABRO1 antibody.",
    "ncbi_link": "GFP: 
Abro1: 109359
ABRO1: 109359"
  },
  {
    "caption": "ELISA analysis of IL-1β secretion from HMDMs transduced with lentiviruses expressing shCon or shABRO1 prior to stimulation with control medium (Con), LPS or LPS plus ATP. Cell lysates were immunoblotted with anti-ABRO1 and anti-GAPDH antibodies.",
    "ncbi_link": "ABRO1: 23172"
  },
  {
    "caption": "Abro1+/+ and Abro1−/− BMDMs were left untreated (Con), treated with LPS alone (LPS) or pretreated with LPS and then stimulated with nigericin, silica, MSU, MDP, Alum, poly (dA: dT), flagellin or LTx (Anthrax Lethal Factor). CBA analysis of IL-1β secretion in the culture supernatants.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Representative immunoblot analysis of cleaved caspase-1 and IL-1β in culture supernatants (SN) of LPS-primed Abro1+/+ and Abro1−/− BMDMs treated with ATP, nigericin, MSU, flagellin or poly (dA: dT).",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Flow cytometric analysis of caspase-1 activity in LPS-primed Abro1+/+ and Abro1−/− BMDMs stimulated with nigericin for indicated times.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Immunostaining of endogenous ASC specks in LPS-primed Abro1+/+ and Abro1−/− BMDMs left untreated or treated with nigericin or poly (dA:dT). Scale bars, 10 μm. Quantification of ASC specks from (H) was performed by counting cells in five random areas of each image in triplicate experiments and described as a percentage of ASC specks for total cell nuclei. At least 100 cells from each treatment condition were quantified. UD, undetectable.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "LPS-primed Abro1+/+ and Abro1−/− BMDMs were left untreated or treated with ATP. Immunoblot analysis of NLRP3 and ASC protein in cell lysates immunoprecipitated with anti-ASC antibody.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "WT, Abro1−/− and Nlrp3−/− mice were intraperitoneally injected with MSU (1 mg per mouse) or vehicle (PBS) for 6 h. ELISA of IL-1β and TNF-α in the peritoneal lavage fluid (A). n = 6 for PBS groups and n = 12 for MSU groups.",
    "ncbi_link": "Abro1: 109359
Nlrp3: 216799"
  },
  {
    "caption": "WT, Abro1−/− and Nlrp3−/− mice were intraperitoneally injected with MSU (1 mg per mouse) or vehicle (PBS) for 6 h. Flow cytometric analysis of peritoneal cell exudates (B). n = 6 for PBS groups and n = 12 for MSU groups.",
    "ncbi_link": "Abro1: 109359
Nlrp3: 216799"
  },
  {
    "caption": "Abro1+/+ and Abro1−/− mice were intraperitoneally injected with MSU (1 mg per mouse). Flow cytometric analysis of caspase-1 activity in peritoneal exudate monocytes and neutrophils. n=12 per group.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Abro1+/+ and Abro1−/− mice were intraperitoneally injected with Alum (1 mg per mouse) or vehicle (PBS) for 6 h. ELISA of IL-1β in the peritoneal lavage fluid (D) n = 6 for PBS groups and n = 12 for Alum groups.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Abro1+/+ and Abro1−/− mice were intraperitoneally injected with Alum (1 mg per mouse) or vehicle (PBS) for 6 h. flow cytometric analysis of peritoneal cell exudates (E). n = 6 for PBS groups and n = 12 for Alum groups.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Survival of Abro1+/+ and Abro1−/− mice subjected to LPS (15 mg/kg). n=20 per group.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "ELISA of serum IL-1β from Abro1+/+ and Abro1−/− mice 3 h after intraperitoneal injection of LPS (15mg/kg) or vehicle (PBS). n = 6 for PBS groups and n = 12 for LPS groups.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Flag-ABRO1 and Myc-tagged NLRP3, ASC or pro-casapase-1 (Pro-Casp-1). Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-c-Myc agarose.",
    "ncbi_link": "Flag: 
Myc: 
pro-casapase-1: 
Pro-Casp-1: 
ABRO1: 23172
NLRP3: 114548
ASC: 29108"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Flag-ABRO1 and Myc-tagged NLRP3 or NLRP3 deletion mutants as indicated in (F). Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-c-Myc agarose.",
    "ncbi_link": "Flag: 
Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Myc-NLRP3 and Flag-tagged ABRO1 or ABRO1 deletion mutants as indicated in (H). Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Myc-ABRO1 and Flag-tagged NLRP3 (WT), NLRP3 (S194D), or NLRP3 (S194A). Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "HEK-293T cells transfected with various combinations (above lanes) of plasmids encoding Myc-ABRO1 and Flag-NLRP3 (WT) or Flag-NLRP3 (S194A) were treated with or without 5 μM Anisomycin for 2 h. Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "HEK-293T cells transfected with various combinations (above lanes) of plasmids encoding Myc-ABRO1 and Flag-NLRP3 (WT) or Flag-NLRP3 (S194D) were treated with or without 100 nM SP600125 for 2 h. Immunoblot analysis of Myc- and Flag-tagged proteins in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "WT and Nlrp3S194A/S194A BMDMs were pretreated with or without 5 μM Anisomycin for 2 h and then left untreated or treated with 100 ng/ml LPS for 1 h. Immunoblot analysis of NLRP3 and ABRO1 proteins in cell lysates immunoprecipitated with control IgG or anti-ABRO1 antibody.",
    "ncbi_link": "Nlrp3: 216799"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Myc-NLRP3, Flag-ABRO1 and HA-ubiquitin (HA-Ub), HA-Ub K48 only or K63 only. Before collection, cells were treated with MG132 (10 μM) for 6 h. Immunoblot analysis of NLRP3 ubiquitination (detected by anti-HA antibody) in cell lysates immunoprecipitated with anti-c-Myc agarose.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
ABRO1: 23172
NLRP3: 114548
Ub: 7314
ubiquitin: 7314"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding HA-Ub, Flag-ABRO1, and NLRP3 truncations as indicated. Before collection, cells were treated with MG132 (10 μM) for 6 h. Immunoblot analysis of ubiquitination of NLRP3 truncations (detected by anti-HA antibody) in cell lysates immunoprecipitated with anti-c-Myc agarose.",
    "ncbi_link": "Flag: 
HA: 
ABRO1: 23172
NLRP3: 114548
Ub: 7314"
  },
  {
    "caption": "LPS-primed Abro1+/+ and Abro1−/− BMDMs were left untreated or treated with ATP (left) or nigericin (right). Immunoblot analysis of NLRP3 ubiquitination (detected by mouse anti-ubiquitin antibody) in cell lysates immunoprecipitated with rabbit anti-NLRP3 antibody.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "Nlrp3-/- BMDMs transduced with lentiviruses expressing Flag-NLRP3 (WT) or Flag-NLRP3 (A350V) were left unstimulated or stimulated with LPS or LPS plus ATP. Immunoblot analysis of NLRP3 and NLRP3 (A350V) ubiquitination (detected by mouse anti-ubiquitin antibody) in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
Nlrp3: 216799
NLRP3: 216799"
  },
  {
    "caption": "HEK-293T cells were transfected with various combinations (above lanes) of plasmids encoding Myc-ABRO1, Flag-NLRP3 (A350V) and HA-ubiquitin (HA-Ub). Immunoblot analysis of NLRP3 (A350V) ubiquitination (detected by anti-HA antibody) in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
ABRO1: 23172
NLRP3: 114548
Ub: 7314
ubiquitin: 7314"
  },
  {
    "caption": "Nlrp3-/- BMDMs transduced with lentiviruses expressing Flag-NLRP3 (WT) or Flag-NLRP3 (A350V) were stimulated with or without 100ng/ml LPS for 1 h. Immunoblot analysis of ABRO1 and NLRP3 proteins in cell lysates immunoprecipitated with anti-ABRO1 antibody.",
    "ncbi_link": "Flag: 
Nlrp3: 216799
NLRP3: 216799"
  },
  {
    "caption": "HEK-293T cells transfected with various combinations (above lanes) of plasmids encoding Myc-ABRO1, Flag-NLRP3, and HA-ubiquitin (HA-Ub) were left untreated or treated with 5 μM Anisomycin for 2 h or 100 nM SP600125 for 2 h. Immunoblot analysis of NLRP3 ubiquitination (detected by anti-HA antibody) in cell lysates immunoprecipitated with anti-Flag M2 beads.",
    "ncbi_link": "Flag: 
HA: 
Myc: 
ABRO1: 23172
NLRP3: 114548
Ub: 7314
ubiquitin: 7314"
  },
  {
    "caption": "LPS-primed WT and Nlrp3S194A/S194A BMDMs were left untreated or treated with ATP. Immunoblot analysis of NLRP3 ubiquitination (detected by mouse anti-ubiquitin antibody) in cell lysates immunoprecipitated with rabbit anti-NLRP3 antibody.",
    "ncbi_link": "Nlrp3: 216799"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− BMDMs were treated with or without LPS for 1 h. Before LPS treatment, Brcc3−/− BMDMs were pretreated with MG132 (10 μM) for 6 h to rescue the expression of ABRO1. Immunoblot analysis of NLRP3 and ABRO1 proteins in cell lysates immunoprecipitated with anti-ABRO1 antibody.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Abro1+/+ and Abro1−/− BMDMs were treated with or without LPS for 1 h. Before LPS treatment, Abro1−/− BMDMs were pretreated with MG132 (10 μM) for 6 h to rescue the expression of BRCC3. Immunoblot analysis of NLRP3 and BRCC3 proteins in cell lysates immunoprecipitated with anti-BRCC3 antibody.",
    "ncbi_link": "Abro1: 109359"
  },
  {
    "caption": "A constant amount of Myc-NLRP3 plasmid together with an increasing amount of Myc-ABRO1 plasmid were co-transfected in HEK-293T cells. Immunoblot analysis of NLRP3 and BRCC3 from the cell lysates immunoprecipitated with control IgG or anti-BRCC3 antibody.",
    "ncbi_link": "Myc: 
ABRO1: 23172
NLRP3: 114548"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− BMDMs transduced with lentiviruses expressing GFP, ABRO1-GFP or BRCC3-GFP were treated with LPS and nigericin. Immunoblot analysis of NLRP3 ubiquitination (detected by mouse anti-NLRP3 antibody) in cell lysates immunoprecipitated with rabbit anti-NLRP3 antibody",
    "ncbi_link": "GFP: 
ABRO1: 109359
Brcc3: 210766
BRCC3: 210766"
  },
  {
    "caption": "Abro1+/+, Abro1−/−, BMDMs transduced with lentiviruses expressing GFP, ABRO1-GFP or BRCC3-GFP were treated with LPS and nigericin. Immunoblot analysis of NLRP3 ubiquitination (detected by mouse anti-NLRP3 antibody) in cell lysates immunoprecipitated with rabbit anti-NLRP3 antibody",
    "ncbi_link": "GFP: 
Abro1: 109359
ABRO1: 109359
BRCC3: 210766"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− BMDMs transduced with lentiviruses expressing GFP, ABRO1-GFP or BRCC3-GFP CBA analysis of IL-1β in culture supernatants",
    "ncbi_link": "GFP: 
ABRO1: 109359
Brcc3: 210766
BRCC3: 210766"
  },
  {
    "caption": "Abro1+/+, Abro1−/−, BMDMs transduced with lentiviruses expressing GFP, ABRO1-GFP or BRCC3-GFP CBA analysis of IL-1β in culture supernatants",
    "ncbi_link": "GFP: 
Abro1: 109359
ABRO1: 109359
BRCC3: 210766"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− BMDMs were left untreated (Con), treated with LPS alone (LPS) or pretreated with LPS and then stimulated with ATP, nigericin, MSU, Alum, poly (dA:dT) or flagellin. CBA analysis of IL-1β secretion in the culture supernatants.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Immunoblot analysis of cleaved caspase-1 and IL-1β in culture supernatants (SN) of LPS-primed Brcc3+/+ and Brcc3−/− BMDMs treated with ATP, nigericin, MSU, flagellin, and poly (dA: dT).",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Immunostaining of endogenous ASC specks in LPS-primed Brcc3+/+ and Brcc3-/- BMDMs left untreated or treated with nigericin or poly (dA:dT). ASC speck positive cells were counted and analyzed as described in Fig. 1I. UD, undetectable.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "LPS-primed Brcc3+/+ and Brcc3−/− BMDMs were left unstimulated or stimulated with nigericin. Immunoblot analysis of NLRP3 ubiquitination (detected by mouse anti-ubiquitin antibody) in cell lysates immunoprecipitated with rabbit anti-NLRP3 antibody.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Survival of Brcc3+/+ and Brcc3−/− mice subjected to LPS (15 mg/kg). n=20 per group.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "ELISA of serum IL-1β from Brcc3+/+ and Brcc3−/− mice 3 h after intraperitoneal injection of LPS (15mg/kg) or vehicle (PBS). n = 6 for PBS groups and n = 12 for LPS groups.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− mice were intraperitoneally injected with MSU (1 mg per mouse) or vehicle (PBS) for 6 h. ELISA of IL-1β and TNF-α in the peritoneal lavage fluid (G)",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "Brcc3+/+ and Brcc3−/− mice were intraperitoneally injected with MSU (1 mg per mouse) or vehicle (PBS) for 6 h. flow cytometric analysis of peritoneal cell exudates (H). n = 6 for PBS groups and n = 12 for MSU groups.",
    "ncbi_link": "Brcc3: 210766"
  },
  {
    "caption": "(A, B) Localization of oskar mRNA in wild-type (A) and in Tm1eg9/Tm1eg9 (B) egg-chambers.",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(C) Kymograph of oskMS2-GFP mRNPs (cyan) travelling along polarity marked MTs (red, EB1 protein) in an ex vivo ooplasmic preparation. White dashed arrow shows the growing plus tip of the MT. Scale bars represent 1 s and 1 µm, respectively.(D) Distribution of oskMS2-GFP mRNP runs towards plus (white) and minus ends (grey). Numbers within the bars indicate number of runs. P value of Chi2 test against wild-type is indicated above each bar.",
    "ncbi_link": "osk: 41066"
  },
  {
    "caption": "(E, F) oskar mRNA (green) and Oskar protein (magenta) distribution in Tm1eg1/Tm1eg9 egg-chambers expressing oskarMS2(6x) (E) or oskarMS2(6x) and Khc401-MCP (F).",
    "ncbi_link": "Khc: 36810
oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(G) oskar mRNA (magenta) distribution in Tm1eg1/Tm1eg9 egg-chambers rescued with EmGFP-Tm1-I (green). Scale bars represent 50 µm.",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(A-B\") Colocalization of oskMS2-mCherry (red, A, B) (A', B') with Khc-EGFP (green, A) (A') or with EmGFP-Tm1-I (green B) (B') in ex vivo ooplasmic preparations.(C) Fraction of oskMS2-MCP-mCherry mRNPs located non-randomly within a 200 nm distance of one of the indicated GFP tagged protein particles in ex vivo ooplasmic preparations. MCP indicates MCP-EGFP which, like MCP-mCherry, can bind to MS2 loops. Staufen (Stau) is a dsRNA binding protein and bona fide partner of oskar mRNA (St Johnston et al., 1991; St Johnston et al., 1992). All values are significantly different from zero (p<10-3, one sample t-test).(D) Fraction of oskMS2-mCherry mRNPs co-localizing (max. 200 nm) non-randomly with Khc-EGFP particles in wild-type and in Tm1eg1/Tm1eg9 ooplasms in presence of two (white) or one (grey) copy of endogenous Khc.(C, D) P values of two sample t-tests are indicated above the relevant bar pairs. Numbers indicate the number of particle clusters (160 mRNPs in each) and the number of preparations (in brackets) analysed. Error bars represent 95% confidence intervals.",
    "ncbi_link": "Khc: 36810
osk: 41066
oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(A, B) Kymographs of oskMS2-GFP mRNPs (green) associated with Khc-mKate2 (A, red) and mCherry-Tm1-I/C (B, red) ex vivo. Arrows indicate motile RNPs in stable complex with Khc (A) or Tm1-I/C (B), the arrowheads point to non-motile oskMS2-RNPs showing no obvious accumulation of the tagged protein. Note that mCherry-Tm1-I was exposed twice as long as Khc-mKate to obtain comparable red fluorescence signals. Scale bars represent 1 µm and 1 second, respectively.(C-E) Relative Khc-mKate2 (C), mCherry-Tm1-I/C (D) coverage of motile (white) and non-motile (grey) oskMS2-GFP trajectories. Numbers within the boxes indicate the number of trajectories and the number of ooplasms (in brackets) analysed. Percentages above the plots show the fraction of RNPs that were found stably and reliably associating with the indicated protein (for at least half of the duration of the trajectory, p<0.01, binominal distribution, see also Fig EV2B). P values of pairwise Mann-Whitney U tests are indicated above the boxplots.",
    "ncbi_link": "Khc: 36810
osk: 41066
Tm1: 41852"
  },
  {
    "caption": "(C-E) Relative GFP-Staufen (E) coverage of motile (white) and non-motile (grey) oskMS2-GFP trajectories. Numbers within the boxes indicate the number of trajectories and the number of ooplasms (in brackets) analysed. Percentages above the plots show the fraction of RNPs that were found stably and reliably associating with the indicated protein (for at least half of the duration of the trajectory, p<0.01, binominal distribution, see also Fig EV2B). P values of pairwise Mann-Whitney U tests are indicated above the boxplots.",
    "ncbi_link": "osk: 41066"
  },
  {
    "caption": "(F) Example kymograph of Khc molecules (red) associating with an oskMS2-GFP mRNP (green) before and during its run. White arrowheads indicate two association events, yellow arrow indicates the onset of motility. Scale bars represent 5 µm and 1 second, respectively.(G) Frequency of Khc-mKate2 appearance on motile (white), before (motility-primed, checked) and after (dotted) the onset of motility, and non-motile (grey) oskMS2-GFP trajectories. Fractions within the bars indicate number of association events that lasted longer than a single frame over the total number of frames analysed. Indicated P values show results of pairwise Fisher's exact test. The Khc association frequency observed on RNPs before (checked) and during (dotted) their motility is not significantly different from wild-type motile RNP controls (p>0.01).",
    "ncbi_link": "Khc: 36810
osk: 41066"
  },
  {
    "caption": "(A) Western blots of oskar mRNP components (Staufen, Bruno and Y14) and motor associated proteins (Khc, BicD, Dic) co-immunoprecipitated with EmGFP-Tm1-I from ovarian lysates. Protein marker bands and their molecular weight in kDa are indicated.",
    "ncbi_link": "oskar: 41066"
  },
  {
    "caption": "(C) qRT-PCR of EmGFP-Tm1-I and control Flag-Myc-GFP and bead alone (w1118) bound oskar and gapdh RNAs after stringent washes (mean ± s.e.m., N = 3).",
    "ncbi_link": "gapdh: 
oskar: 41066"
  },
  {
    "caption": "(A, B, C) Confocal image of a Tm1eg9 homozygous egg-chamber expressing EmGFP-Tm1-I (green) and Khc-mKate2 (magenta). oskar mRNA labelled with osk1-5 FIT probes(Hovelmann et al., 2014) is in yellow.(B', C') oskar mRNPs co-localizing with both EmGFP-Tm1-I and Khc-mKate2. Colors indicate the maximal co-localization distance (C'). Panels B-C' represent the boxed regions in panel A.",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(D, E) Localization of Khc-mKate2 (green) and oskar mRNA (magenta) in wild-type and Tm1gs mutant nurse cells.(F, G) Fraction of oskar mRNPs co-localizing with Khc-mKate (dark grey), EmGFP-Tm1-I (white), or both of these proteins (light grey) in the oocyte (F) or in the nurse cells (G) (max. colocalization distance is 250 nm). None of the values are significantly different from each other (one-way ANOVA, p>10-3). Horizontal dashed lines indicate the expected value of observing both proteins in an oskar mRNP if the interactions are independent (see Fig EV3C and D). Significance of the observed co-localization values versus the expected values are shown.(H) Fraction of oskar mRNPs co-localizing with Khc-mKate in wild-type and Tm1gs mutant nurse cells when half or all Khc molecules are labelled (as indicated above the graph). P values of pair-wise t-tests are indicated.(I) Fraction of oskar mRNPs co-localizing with free mCherry in wild-type nurse cells used as negative control. The measured fraction (~1.6%) is significantly different from zero (one sample t-test). All other measured co-localization values are significantly different form this negative control (p<0.001, one-way ANOVA).(F-I) Numbers indicate the number of particle clusters (100 oskar mRNPs in each) and the number of egg-chambers (in brackets) analysed. Error bars represent 95% confidence intervals. All values (F-I) are significantly different from zero (p<10-3, one sample t-test).",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(A-C) Localization of EmGFP-Tm1-I (A) oskar mRNA (B) and Khc (C) around the nurse cell nuclear envelope (magenta, WGA staining).(D-F) Mean distribution profile of Khc (D) mKate2-Tm1-I, EmGFP-Tm1-I (E) and oskar mRNA (F) around the NE of nurse cells (marked with a dotted vertical line). Genotypes are indicated as follows: wild-type control with solid black line (D-F), oskar RNA null with solid grey line (D, E), Tm1eg9/Tm1eg9 with dotted black line (D, F) Lines indicate mean and 95% confidence intervals. We analysed the accumulation of mKate2-Tm1-I instead of EmGFP-Tm1-I due to unexpected GFP expression from the oskar0 allele.",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(G) Khc accumulation around the NE. To calculate accumulation the signal intensity measured at the position of the peak observed in the wild-type control (D, arrowhead, 356±17.6 nm away from NE) was divided by the signal intensity 2 s.d. away (d, arrow, at 356+2*410 nm). P values of pairwise Mann-Whitney U tests against wild-type control or Tm1gs rescued with EmGFP-Tm1-I are indicated above the boxplots. Numbers indicate the number of nuclei and the number of egg-chambers (in brackets) analysed.(H-K) Khc accumulation around the NE of nurse cells over-expressing EmGFP-Tm1-I within Tm1eg9/Tm1eg9 (H), and oskar RNA null egg-chambers (I) expressing either the oskar 3' UTR (J) or oskar Δi(1,2,3) (K).",
    "ncbi_link": "oskar: 41066
Tm1: 41852"
  },
  {
    "caption": "(A-E) Mean oskar mRNA distribution (green, detected by conventional FISH) within oocytes in which oskar mRNA is substituted by oskar Δi(1,2,3) mRNA (A, B), oskar 3'UTR mRNA (D) and that (in addition) over-express EmGFP-Tm1-I (B, D and E). Wild-type control (C) and oocytes expressing Khc RNAi and EmGFP-Tm1-I (E). Magenta indicates standard deviation of the distribution of oskar mRNA. Scale bar is 10% of total oocyte length (C).(F) Position of the oskar mRNA center of mass relative to the geometric center of the oocyte (dotted horizontal line) along the anteroposterior (AP) axis. Posterior pole is the top of the chart. P values of pairwise Mann-Whitney U tests are indicated. Numbers indicate number of oocytes analysed.",
    "ncbi_link": "Khc: 36810
oskar: 41066
Tm1: 41852"
  }
]